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Title: The Propaganda for Reform in Proprietary Medicines, Vol. 2 of 2
Author: Various
Language: English
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THE PROPAGANDA FOR REFORM
IN
Proprietary Medicines
VOLUME 2
Part I Reports of the Council
Part II Contributions from the Laboratory
Part III Journal Contributions: Proprietary Products
Part IV Journal Contributions: Miscellany
PRESS OF AMERICAN MEDICAL ASSOCIATION, FIVE HUNDRED AND THIRTY-FIVE
NORTH DEARBORN STREET,--CHICAGO
1922
COPYRIGHT, 1922 BY THE AMERICAN MEDICAL ASSOCIATION
PREFACE TO VOLUME 2
There were nine editions of the first volume of The Propaganda for
Reform in Proprietary Medicines. The ninth edition contained the most
important reports of the Council on Pharmacy and Chemistry and of the
Chemical Laboratory. It contained also those articles from _The Journal
of the American Medical Association_ (up to, and including, 1916)
which dealt with the problems of proprietaryship in medicine and the
furtherance of rational drug therapy.
The present volume contains similar material covering the period from
January, 1917, to April, 1922, inclusive. Like Volume 1, this volume is
divided into four parts:
Part I. THE COUNCIL ON PHARMACY AND CHEMISTRY: This section presents
the principles and rules which govern the Council in the examination of
medicaments, together with articles and reports bearing on the work of
the Council, and the most important reports of the Council from 1917 to
April, 1922, inclusive.
Part II. THE A. M. A. CHEMICAL LABORATORY: This section, besides
presenting the aims and objects of the Association’s Chemical
Laboratory, also outlines some of the Laboratory’s work which is of
particular interest to physicians.
Part III. CONTRIBUTIONS FROM THE JOURNAL: Proprietary Products: This
part contains articles on proprietary medicinal preparations and the
methods by which they are exploited, which have appeared in _The
Journal A. M. A._
Part IV. CONTRIBUTIONS FROM THE JOURNAL: MISCELLANY: In this section
are articles dealing with matters of interest to the medical profession
but not coming strictly under the classification of proprietary
medicinal preparations.
A comparison of the material that has appeared in Volume 1 of The
Propaganda for Reform with that which appears in this volume will
reveal the changing conditions in the proprietary medicine field. Many
of the reports in the first volume brought out the fact that medicinal
preparations were at that time foisted on the profession with false
claims of composition; reports of this character are less conspicuous
in the present volume. Many of the reports in Volume 2 deal with
unwarranted therapeutic claims, especially those advanced for animal
organ preparations, serums, vaccines, preparations for intravenous
medication, etc. The present volume will also be found of interest in
its portrayal of the changed conditions in the proprietary medicine
business brought about by the World War.
Special attention is directed to the index in this volume. It is, in
effect, a bibliography, including references not only to articles
in this book but also (1) to articles which appeared in Volume 1;
(2) to articles on the same general subject in _The Journal of the
American Medical Association_, and (3) to the articles appearing in
the annual reports of the Council on Pharmacy and Chemistry and of the
A. M. A. Chemical Laboratory, but not reprinted in either volume of the
Propaganda for Reform in Proprietary Medicines.
PREFACE TO VOLUME 1: NINTH EDITION
From time to time _The Journal of the American Medical Association_ has
published the reports of the Council on Pharmacy and Chemistry and the
Chemical Laboratory, as well as other matter on proprietary medicines.
Repeated requests for some of the matter have led to the compilation
of “The Propaganda for Reform in Proprietary Medicines,” which, in the
present volume, attains its ninth edition.
The seventh, eighth and ninth editions have been compiled on slightly
different principles from their predecessors. The therapeutic reform
work of _The Journal_ and of the Association’s Chemical Laboratory was
at first confined almost entirely to the criticism and analysis of the
so-called ethical proprietaries. This was right; the medical profession
owed it to the public to combat the nostrum evil within its own ranks.
As the more flagrant evils of the “ethical proprietary” question were
mitigated, the Association has turned the light on the more widespread
and dangerous “patent medicine” evil. The articles devoted to “patent
medicines” or quackery being naturally of greater interest to the
general public than to the medical profession, the number of inquiries
from laymen regarding various quacks and nostrums has steadily
increased. It has been thought best, therefore, to publish separately
all of the matter from _The Journal_ relative to quackery and to those
nostrums exploited only or chiefly to the public, and to include in the
Propaganda for Reform practically none of the matter that is of direct
interest primarily to laymen. In one or two instances in which the
subjects were of equal interest to the profession and to the public,
matter that has already appeared in “Nostrums and Quackery” is also
given here; but as a general rule the contents of the ninth edition
of “The Propaganda for Reform” are of strictly professional interest.
Those physicians who are desirous of obtaining in convenient form the
matter dealing with “patent medicines” should order the book “Nostrums
and Quackery” or the various pamphlets on the same subjects that have
been issued since “Nostrums and Quackery” came from the press.
The ninth edition of “Propaganda for Reform” contains a number of new
articles, greatly increasing the size of the book. It also contains
one novel feature which greatly enhances its value. The index includes
references not only to articles in the book, but also to matter on
proprietaries not accepted by the Council on Pharmacy and Chemistry
which appeared in _The Journal of the American Medical Association_ and
elsewhere. This index makes of this edition of “Propaganda for Reform”
a very full work of reference on proprietaries which are undeserving of
recognition. It should be understood, however, that not all articles
indexed are condemned; some are merely discussed and compared.
RESOLUTION ENDORSING THE WORK OF THE COUNCIL
ON PHARMACY AND CHEMISTRY
Presented at the San Francisco Session and Signed by All the Members
of the House of Delegates in Attendance
+-------------------------------------------------------------------+
| _Resolved_, We, Members of the House of Delegates of the American |
| Medical Association, believe that every effort must be made to |
| do away with the evils which result from the exploitation of the |
| sick for the sake of gain. Earnestly believing that the continued |
| toleration of secret, semisecret, unscientific or untruthfully |
| advertised proprietary medicines is an evil that is inimical to |
| medical progress and to the best interest of the public, we |
| declare ourselves in sympathy with, endorse and by our best |
| efforts will further, the work which has been, and is being, done |
| by the Council on Pharmacy and Chemistry of the American Medical |
| Association in the attempt to eliminate this evil. |
+-------------------------------------------------------------------+
TABLE OF CONTENTS
PART I: COUNCIL REPORTS
PAGE
Foreword 1
Official Rules of the Council on Pharmacy and Chemistry 3
The Council on Pharmacy and Chemistry, Present and Future 12
“Accepted by the Council on Pharmacy and Chemistry” 19
Helping the Council 20
Delays in Passing on Products 20
Cooperation of the Pharmaceutical Houses 21
Budwell’s Emulsion of Cod-Liver Oil, Nos. 1 and 2 22
Rheumalgine 23
Gray’s Glycerine Tonic 24
Tongaline and Ponca Compound 26
Alfatone 28
Uricsol 30
Jubol 31
Urodonal 32
Formamint 33
Hydragogin 41
Filudine 41
Lactopeptine and Elixir Lactopeptine 43
Iodum-Miller and Iod-Izd-Oil (Miller’s) 49
Elixir Iodo-Bromide of Calcium Comp. “Without Mercury” and
“With Mercury” 52
Lecithin Preparations Omitted from N. N. R. 53
Proprietary Names for Liquid Petrolatum 55
Seng 55
Frosst’s Blaud Capsules 56
Tyree’s Elixir of Buchu and Hyoscyamus Compound 57
Hydroleine 58
Curative Vaccine, Bruschettini 58
Stearn’s Wine 59
Protonuclein and Protonuclein Beta 59
Hydropsin 61
Digitalysatum 63
So-Called Secretin Preparations 64
Has Secretin a Therapeutic Value? 65
Radio-Rem 79
Olio-Phlogosis 79
The Hypophosphite Fallacy 80
Pulvoids Calcylates 85
Sulfuryl Monal 86
Mark White Goiter Serum and Mark White Iodinized Oil 87
Kora-Konia 92
The Therapeutic Value of the Glycerophosphates 93
Hydras 96
Bromin-Iodin Compound 97
Ammonium Hypophosphite Omitted from N. N. R. 98
Alphozone Omitted from N. N. R. 99
Calcium Glycerophosphate and Sodium Glycerophosphate Omitted
from N. N. R. 99
Gardner’s Syrup of Ammonium Hypophosphite Omitted
from N. N. R. 100
Gluten Products Made by the Kellogg Food Company 100
Iodo-Mangan Omitted from N. N. R. 106
Liquid Albolene 106
Naphey’s Medicated Uterine Wafers 107
Nujol 108
Pulvoids Natrium Compound 108
Saloform 110
Secretogen 110
Iron Citrate Green 115
Aspirin 116
Pil. Cascara Compound-Robins 117
Casta-Flora 118
Firwein 119
Firolyptol Plain and Firolyptol with Kreosote 120
Biniodol 121
Comparative Symptoms Resulting from the Use of Several Oily
Suspensions of Red Mercuric Iodid (Mercury Biniodid) 123
Corpora Lutea (Soluble Extract), Parke, Davis & Co. 128
Wheeler’s Tissue Phosphates 129
The Claimed Galactagogue Effects of Nutrolactis and
Goat’s Rue Not Substantiated 131
The Alleged Galactagogue Action of Galega and Nutrolactis 131
The Russell Emulsion and the Russell Prepared Green Bone 134
Brom-I-Phos 136
Creosote-Delson and Creofos 137
Triner’s American Elixir of Bitter Wine 139
Trimethol 140
Ferrivine, Intramine and Collosol Iodine 144
Eskay’s Neuro Phosphates 146
K-Y Lubricating Jelly 147
Ziratol 148
Gonosan 150
Alcresta Ipecac 153
Iodeol and Iodagol 154
Capsules Bismuth Resorcinol Compound Not Admitted to N. N. R. 157
Dixon’s Tubercle Bacilli Extract and Dixon’s Suspension of
Dead Tubercle Bacilli 158
Formosol 158
Iodolene, a Solution of Iodin in Liquid Petrolatum,
Inadmissible to N. N. R. 159
Kalak Water 160
Minson’s Soluble Iodin “Kelpidine” Not Admitted to N. N. R. 161
Nutone 162
Tri-Arsenole, L. O. Compound No. 1 and L. O. Compound No. 2 163
Unctol 166
V-E-M (Schoonmaker Laboratories, Inc.) 166
Hemo-Therapin 168
Venosal 169
Secretin-Beveridge and the U. S. Patent Law 170
The Question of the Stability of Secretin 171
Need for Patent Law Revision 177
Surgodine 180
Medeol Suppositories 181
Guaiodine 183
Several “Mixed” Vaccines Not Admitted to N. N. R. 184
Ophthalmol-Lindemann 189
Silvol Ineligible for N.N.R 189
Katharmon 191
Iodinized Emulsion (Scott) and Creosotonic (Scott) 192
Campetrodin and Campetrodin No. 2 193
Carminzym 194
Phillips’ Phospho-Muriate of Quinine Comp 197
B. Iodine and B. Oleum Iodine 198
B. Iodine Products 199
Antithyroid Preparations (Antithyroidin-Moebius and
Thyreoidectin) Omitted from N. N. R. 202
Cephaelin and Syrup Cephaelin-Lilly Omitted from N. N. R.
and Syrup Emetic-Lilly Not Accepted 203
Colalin Omitted from N. N. R. 203
Foral 204
Granular Effervescent Bromide and Acetanilid Compound-Mulford 206
Holadin and Bile Salt Mixtures 207
Liquor Santaiva, S. & D., Omitted from N. N. R. 211
Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod
Liver Oil, Maltzyme Ferrated and Maltzyme with Yerba Santa
Omitted from N. N. R. 211
Methaform Omitted from N. N. R. 212
Pineal Gland, Red Bone-Marrow and Thymus Gland and Their
Preparations Omitted from N. N. R. 213
Piperazine and Lycetol Omitted from N. N. R. 214
Stanolind Liquid Paraffin Omitted from N. N. R. 214
Westerfield’s Digitalis Tablets 215
Xeroform-Heyden and Bismuth Tribromphenate-Merck Omitted
from N. N. R. 216
Cream of Mustard Refused Recognition 218
“Pluriglandular” Mixtures 218
Cerelene Not Admitted to N. N. R. 219
Collosol Cocaine Not Admitted to N. N. R. 221
Cuprase Not Admitted to N. N. R. 222
Collosol Preparations 223
Pulvoids Calcylates Compound 226
Proteogens of the Wm. S. Merrell Company 227
“Arsenoven S. S.” and “Arseno-Meth-Hyd” 231
Hormotone and Hormotone Without Post-Pituitary 234
Formaldehyde Lozenges 235
Lavoris 237
Medinal 239
Omission of Cotarnin Salts (Stypticin and Styptol)
from N. N. R. 240
Micajah’s Wafers and Micajah’s Suppositories 241
Alkalithia 242
Arhovin Omitted from N. N. R. 243
Chloron, Chlorax and Number “3” 244
Elarson Omitted from N. N. R. 248
Iodiphos 249
Mervenol and Armervenol Not Admitted to N. N. R. 249
Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano)
Not Accepted for N. N. R. 251
Soamin Omitted from N. N. R. 253
Some Mixed Vaccines Not Admitted to N. N. R. 254
Somnoform 255
Tablets Formothalates 256
Triple Arsenates with Nuclein 256
“Anti-Pneumococcic Oil” and the Use of Camphor in Pneumonia 257
Dial “Ciba” 259
Apothesine 260
Eumictine 262
Platt’s Chlorides 263
Anti-Tuberculous Lymph Compound (Sweeny) and Anti-Syphilitic
Compound (Sweeny) 266
Syrup Leptinol (Formerly Syrup Balsamea) 268
Formitol Tablets, II 271
Sukro-Serum and Aphlegmatol 273
Supsalvs Not Admitted to N. N. R. 274
Hypodermic Solution No. 13, Iron, Arsenic and Phosphorus
Compound Not Accepted for N. N. R. 275
Parathesin Not Admitted to N. N. R. 276
Chlorlyptus 277
Aquazone (Oxygen Water) 290
Coagulen-Ciba Omitted from N. N. R. 290
Ferric Cacodylate Omitted from New and Non-Official Remedies 292
Libradol 293
Helmitol Omitted from N. N. R. 295
Spirocide Not Admitted to N. N. R. 296
Digifolin-Ciba Not Admitted to N. N. R. 298
Some of Loesser’s Intravenous Solutions 299
“National Iodine Solution” Not Admitted to N. N. R. 300
Mon-Arsone Not Admitted to N. N. R. 302
Oxyl-Iodide Not Admitted to N. N. R. 304
Quassia Compound Tablets 306
Toxicide 307
Pil. Mixed Treatment (Chichester) 310
Atophan Omitted from N. N. R. 313
Urotropin Omitted from N. N. R. 316
Styptysate Not Admitted to N. N. R. 318
Lipoidal Substances (Horovitz) Not Admitted to N. N. R. 320
Yeast Preparations and Vitamin B Concentrates 321
PART II: CONTRIBUTIONS FROM THE A. M. A. CHEMICAL LABORATORY
The Chemical Laboratory of the American Medical Association 322
The Work of the American Medical Association Chemical
Laboratory 322
Lead in “Akoz” 328
Sodium Acetate in Warming Bottles 329
Anti-Syphilitic Compound (Sweeny) 330
“Ambrine” and Paraffin Films 330
The Stability of Iodine Ointments 337
Iodolene and the Solubility of Iodin in Liquid Petrolatum 344
American-Made Synthetic Drugs--I 344
Standardization of Commercial Bismuth Tribromphenate 348
Standardization of Procain and Examination of the
Market Supply 355
Deterioration of Sodium Hypochlorite Solutions 358
Syphilodol 359
Cerelene 362
Dr. De Sanctis’ Rheumatic and Gout Pills 363
Iodex and Liquid Iodex 365
PART III: CONTRIBUTIONS FROM THE JOURNAL: PROPRIETARY PRODUCTS
Iodin in Liquid Petrolatum 367
American-Made Synthetic Drugs--II 369
Nostrums in Retrospect 379
Bell-Ans (Pa-Pay-Ans Bell) 380
Anasarcin and Anedemin 383
Pepto-Mangan 387
Cactina Pillets 391
Ammonol and Phenalgin 393
Fellows’ Syrup, and Other Preparations of the Hypophosphites 395
Shotgun Nostrums 398
Tyree’s Antiseptic and Aseptinol 401
Neurosine and the Original Package Evil 404
Anasarcin Advertising 407
Antimeristem-Schmidt 408
Antiphlogistine 409
“Auto-Hemic Serum” 409
“Autolysin” Advertising 413
“Basic Cancer Research” and “Cosmopolitan Cancer Research
Society” 414
Seleni-Bascca 416
Bell-Ans (Papayans, Bell) 418
Campho-Phenique 418
“Cinchophen”: Formerly “Atophan” 419
“Collosols”: An Uncritical English Endorsement 420
Cotton Process Ether 421
Dionol 422
The Eli Products of Eli H. Dunn 424
Glover’s Cancer Serum 425
Glyco-Thymoline and Poliomyelitis 427
Glykeron: Cold Storage Testimonials 428
Gray’s Glycerine Tonic: “Whose Bread I Eat His Song I Sing” 429
Hagee’s Cordial of Cod Liver Oil 429
Hypno-Bromic Compound 430
Intravenous Compound (Loffler) 430
Intravenous Specialties 435
Iodex 436
The William F. Koch Cancer Remedy 437
The Lucas Laboratories’ Products 440
“Phylacogens” 441
Pineoleum Advertising Methods 442
“Proteal Therapy” and Henry Smith Williams 443
Proteogens 445
Pulvane 450
Sal Hepatica 451
Salicon 453
So-Called Secretin Preparations 454
Succus Cineraria Maritima 455
Tekarkin 458
Tyree’s Antiseptic Powder Again 462
Wheeler’s Tissue Phosphates 463
Briefer Paragraphs 465
PART IV: CONTRIBUTIONS FROM THE JOURNAL: MISCELLANY
Albert Abrams, A.M., M.D., LL.D., F.R.M.S. 472
Acetylsalicylic Acid, Not Aspirin 480
The Allied Medical Associations of America 486
“Arsenicals” 491
Beer and Cancer Cures 494
Biologic Therapeutics and Its Commercial Domination 496
Capell’s Uroluetic Test 497
Chemotherapy and Tumors 499
The Direct Sales Company 510
Discoveries and Discoverers 511
“Drug Reform” 513
Drug Therapy: The Fallibility of Textbooks 515
Thomas Webster Edgar 515
Glycerophosphates 520
Influenza Vaccine 520
Intravenous Therapy 522
Iodin Fumes 523
Italian Physico-Chemical Company 524
What is Liquid Petrolatum? 526
The Lowenthal Postgraduate Course 527
Medical Society of the United States 531
The National Formulary--A Review of the Fourth Edition 535
Nonspecific Protein Therapy 536
Willard Ealon Ogden 538
“Patents” 542
Pharmaceutical Barnums 545
The Pharmacopeia 546
Physician’s Stock in Prescription Products 548
Pituitary Gland Preparations 549
Proprietorship in Medicine 550
Philip Rahtjen and His Discoveries 553
Sodium Cacodylate in Syphilis 555
Tablets: Dependability of Dosage 556
Therapeutic Evidence: Its Crucial Test 557
“Vaccines in Toxic Conditions” 560
Vitamins: Their Distribution 561
The William A. Webster Co. and the Direct Pharmaceutical Co. 564
Yeast 566
Briefer Paragraphs 570
THE PROPAGANDA FOR REFORM IN PROPRIETARY MEDICINES
PART I
REPORTS OF THE COUNCIL ON PHARMACY AND CHEMISTRY
FOREWORD
THE COUNCIL ON PHARMACY AND CHEMISTRY
The Council on Pharmacy and Chemistry was established by the
American Medical Association primarily for the purpose of gathering
and disseminating such information as would protect the medical
profession--and thus the public--in the prescribing of proprietary
medicinal articles.
The Council consists of sixteen members, fifteen appointed for a term
of five years without pay, and the sixteenth, a secretary, who is
also the director of the Chemical Laboratory of the American Medical
Association (see Part II).
At the present time (1921) the membership is:
C. L. Alsberg, A.M., M.D., Chief of the Bureau of Chemistry, U. S.
Department of Agriculture, Washington, D. C.
C. W. Edmunds, M.D., Professor of Materia Medica and Therapeutics,
University of Michigan Medical School, Ann Arbor.
R. A. Hatcher, Ph.G., M.D., Professor of Pharmacology, Cornell
University Medical College, New York City.
A. W. Hewlett, M.D., Professor of Medicine, Leland Stanford Junior
University School of Medicine, San Francisco.
John Howland, M.D., Professor of Pediatrics, Johns Hopkins University
Medical Department, Baltimore.
Reid Hunt, M.D., Professor of Pharmacology, Medical School, Harvard
University, Boston.
W. T. Longcope, A.B., M.D., New York.
G. W. McCoy, M.D., Director of the Hygienic Laboratory, U. S. Public
Health Service, Washington, D. C.
Lafayette B. Mendel, Ph.D., Sc.D., Professor of Physiological
Chemistry, Sheffield Scientific School, Yale University, New Haven.
F. G. Novy, Sc.D., M.D., Professor of Bacteriology, University of
Michigan Medical School, Ann Arbor.
W. W. Palmer, B.S., M.D., Bard Professor of Medicine, Columbia
University College of Physicians and Surgeons, New York.
W. A. Puckner, Phar.D., Secretary of the Council, Director of the
Chemical Laboratory of the American Medical Association, Chicago.
L. G. Rowntree, M.D., Sc.D., Professor of Medicine, Mayo Foundation,
Rochester.
G. H. Simmons, M.D., LL.D., Chairman of the Council, Editor of The
Journal of the American Medical Association, Chicago.
Torald Sollmann, M.D., Professor of Pharmacology and Materia Medica,
Western Reserve University School of Medicine, Cleveland.
Julius Stieglitz, Ph.D., Sc.D., Chem.D., Professor of Chemistry,
University of Chicago, Vice-Chairman of the Council, Chicago.
At its first meeting in 1905, the Council began examining the
proprietary and nonofficial medicinal preparations offered to
physicians of the United States, and authorized the publication of
a book (New and Nonofficial Remedies) containing descriptions of
those preparations which were deemed worthy of the consideration of
physicians. It also issued reports (Reports of the Council on Pharmacy
and Chemistry) to the medical profession on those preparations which
were not eligible. The Council adopted a set of rules by which to
measure the eligibility of each preparation for admission to New and
Nonofficial Remedies. These rules were designed primarily to protect
the public--through the medical profession--against fraud, undesirable
secrecy and objectionable advertising in connection with proprietary
medicinal articles. The rules originally adopted have been subjected
to revision from time to time to meet changing conditions. For the
information of those who wish to familiarize themselves with the work
of the Council the rules which are now in force (1921) follow this
introduction. A summary is also to be found in the article, “The Work
of the Council on Pharmacy and Chemistry, Present and Future,” page 12.
Since 1906, the Council has issued New and Nonofficial Remedies
annually. In each issue are listed and described the articles that
stand accepted on January 1 of the year of publication. The book
describes proprietary medicinal articles on the American market that
are found eligible under the rules, and also such nonproprietary,
nonofficial articles as give promise of therapeutic usefulness, listing
the acceptable brands. Articles of a similar character are grouped
together, and each group is preceded by a general discussion for the
purpose of comparison.
Since 1908, the Council has also issued an annual volume, “Reports
of the Council on Pharmacy and Chemistry,” which contains reports
on proprietary medicines that were found inadmissible to New and
Nonofficial Remedies. The reports issued prior to 1916--and deemed of
sufficient interest to physicians--were reprinted in the Propaganda
for Reform in Proprietary Medicines, ninth edition (1916). The more
important reports issued from 1916 to 1921, inclusive, are in this
volume.
While it is the chief function of the Council to investigate and report
on proprietary medicinal preparations, its work has broadened so that
the Council’s work may now be characterized as a propaganda for the
rational use of drugs. Thus, its Committee on Therapeutic Research
encourages the investigation of questions concerning the actions
of drugs. These investigations are brought together in the “Annual
Reports of the Therapeutic Research Committee.” The Council also has a
committee on medical teaching which has issued the publication “Useful
Drugs,” a concise, but thorough and up-to-date, discussion of the more
important drugs. In addition, the Council appointed a committee to
prepare an “Epitome of the U. S. Pharmacopeia and National Formulary,”
in which are presented those portions of the United States Pharmacopeia
and the National Formulary that are of interest to physicians and in
which is given a concise statement of the therapeutic usefulness of
such drugs and preparations.
OFFICIAL RULES OF THE COUNCIL ON PHARMACY AND CHEMISTRY
[May 1, 1921]
Introduction
The following rules have been adopted by the Council primarily with
the object of protecting the medical profession and the public against
fraud, undesirable secrecy and objectionable advertising in connection
with proprietary medicinal articles.
NEW AND NONOFFICIAL REMEDIES.--The book New and Nonofficial Remedies
contains a description of proprietary articles which have been
accepted as conforming to the rules of the Council; and of such simple
nonproprietary and nonofficial substances as seem of sufficient
importance to warrant their inclusion.
MIXTURES.--For admission to N. N. R., proprietary pharmaceutical
mixtures must comply with the rules; and, to determine such compliance,
they will be investigated by the Council. The Council, however,
endorses the principle that prescriptions should be written on the
basis of the therapeutic effects of the individual ingredients. For
this reason, it includes in this book only those mixtures that present
some real advantage. There is also an appendix in which are included
those proprietary articles which, so far as known to the Council,
comply with the rules, but which do not possess sufficient originality
to be admitted to the body of the book.
Rules Governing the Admission of Proprietary Articles to the Book
New and Nonofficial Remedies
DEFINITION OF PROPRIETARY ARTICLES.--The term “proprietary article,”
in this place, shall mean any chemical, drug or similar preparation
used in the treatment of diseases, if such article is protected against
free competition, as to name, product, composition or process of
manufacture, by secrecy, patent, copyright, or by any other means.
_Rule 1._--COMPOSITION.--No article will be accepted for inclusion in
the book New and Nonofficial Remedies, or retained therein, unless its
composition be furnished to the Council for publication. For simple
substances, the scientific name and the chemical formula, rational or
structural, if known, should be supplied. For mixtures, the amount of
each active medicinal ingredient in a given quantity of the article
must be stated. The general composition of the vehicle, its alcoholic
percentage, and the identity of the preservatives must be furnished.
_Rule 2._--IDENTIFICATION.--No article will be accepted or retained
unless suitable tests for determining its composition are furnished to
the Council. In the case of chemical compounds, these shall consist of
tests for identity and purity. In the case of mixtures, description of
methods for determining the amount and active strength of the potent
ingredients shall be furnished, if practicable.
_Rule 3._--DIRECT ADVERTISING.--No article that is advertised to the
public will be accepted or retained; but this rule shall not apply
to: (_a_) disinfectants, germicides and antiseptics, provided the
advertising is limited to conservative recommendations for their use as
prophylactic applications to superficial cuts and abrasions of the skin
and to the mucous surfaces of the mouth, pharynx and nose (but not to
those of the eye, and the gastro-intestinal and genito-urinary tracts)
and provided they are not advertised as curative agents (see comments
to Rule 3); and (_b_) nonmedicinal food preparations, except when
advertised in an objectionable manner.
_Rule 4._--INDIRECT ADVERTISING.--No article will be accepted or
retained if the label, package or circular accompanying the package
contains the names of diseases in the treatment of which the article is
said to be indicated. The therapeutic indications and properties may be
stated, provided such statements do not suggest self-medication. Dosage
may be indicated. (This rule shall not apply to remedies with which
self-medication is altogether improbable, to vaccines and antitoxins
or to directions for administering or applying remedies when similar
immediate, heroic treatment is indicated.)
_Rule 5._--FALSE CLAIMS AS TO ORIGIN.--No article will be accepted or
retained concerning which the manufacturer or his agents make false or
misleading statements as to source, raw material from which made, or
method of collection or preparation.
_Rule 6._--UNWARRANTED THERAPEUTIC CLAIMS.--No article will be accepted
or retained concerning which the manufacturer or his agents make
unwarranted, exaggerated or misleading statements as to the therapeutic
value.
_Rule 7._--POISONOUS SUBSTANCES.--The principal label on an article
containing “poisonous” or “potent” substances must state plainly the
amount of each of such ingredients in a given quantity of the product.
_Rule 8._--OBJECTIONABLE NAMES.--Proprietary names for medicinal
articles will be recognized only when the Council shall deem the use
of such exclusive names to be in the interest of public welfare. Names
which are misleading or which suggest diseases, pathologic conditions
or therapeutic indications will not be recognized (the provision
against therapeutically suggestive names does not apply to serums,
vaccines and antitoxins, or to foods). In the case of pharmaceutical
preparations or mixtures, the name must be so framed as to indicate the
most potent ingredients.
_Rule 9._--PATENTED PRODUCTS AND PROTECTED NAMES.--If the article is
patented--either process or product, or both--the number of such patent
or patents must be furnished to the Council. Furthermore, if the name
of an article is registered, or the label copyrighted, the registration
(trademark) number and a copy of the protected label should be
furnished the Council. In case of registration in foreign countries,
the name under which the article is registered should be supplied.
_Rule 10._--UNSCIENTIFIC AND USELESS ARTICLES.--No article will be
accepted or retained which, because of its unscientific composition,
is useless or inimical to the best interests of the public or of the
medical profession.
Explanatory Comments on the Rules
INTRODUCTION.--The Council on Pharmacy and Chemistry was established
in February, 1905, by the American Medical Association, primarily
for the purpose of gathering and disseminating such information as
will protect the medical profession in the prescribing of proprietary
medicinal articles. In pursuance of this object, the Council examines
the articles on the market as to their compliance with definite rules
designed to prevent fraud, undesirable secrecy and the abuses which
arise from advertising directly or indirectly to the laity. Such
articles as appear to conform to the rules are accepted; and their
essential features are described in the annual publication of the
Council, New and Nonofficial Remedies, if they come within the scope
of this book. These descriptions are based in part on investigations
made by, or under, the direction of the Council, but in part also on
evidence or information supplied by the manufacturer or his agents.
Such interested statements are examined critically, and are admitted
only if they appear to be in conformity with the evidence. It is,
however, manifestly impossible for the Council to investigate the
composition of every complex pharmaceutical mixture, or to check
thoroughly every therapeutic claim; it can give only an unbiased
judgment on the available evidence. Criticisms and corrections of
the descriptions which may aid in the revision of the matter will be
appreciated. The Council judges an article entirely by the facts in
evidence at the time of its admission. Previous noncompliance with the
rules (short of _intentional_ fraud) does not prevent the favorable
consideration of an article which is in accord with existing rules.
Infringements of the rules after acceptance of an article for New and
Nonofficial Remedies, or the discovery that the Council’s information
was incorrect, will cause the acceptance to be reconsidered. An article
is accepted for New and Nonofficial Remedies, and will continue to be
included in the book, with the understanding that serious violations of
the rules, after acceptance, will be followed by the omission of the
article and publication of the reasons for such omission. The Council
desires physicians to understand that the admission of an article does
not imply a recommendation. Acceptance simply means that no conflict
with the rules has been found by the Council.
DURATION OF ACCEPTANCE.--Unless an agreement to the contrary is made
at the time of acceptance, articles admitted to New and Nonofficial
Remedies will be retained for a period of three years, provided that
during that period they comply with the rules and regulations which
were in force at the time of their acceptance. At the end of this
period all articles will be carefully reexamined for compliance with
existing rules. Particular weight will be given to the question as to
whether recent evidence has substantiated claims as to the therapeutic
value of any preparation, this evidence to consist partly of recent
statements in the literature and partly of the general esteem in which
the preparation is held by clinical consultants of the Council. The
reacceptance of articles after such reexamination shall be for three
years unless a shorter period is specified. Any amendments to the
rules, by specific requirements or by interpretation, which may be made
after the acceptance of an article, shall not apply to such article
until the period of acceptance has elapsed. At the end of this period
the article, if it is not eligible under the amended rules, will be
omitted.
THE SCOPE OF NEW AND NONOFFICIAL REMEDIES AND APPENDIX.--To aid
physicians and manufacturers in deciding what articles come within
the scope of this book, or, in other words, to enable physicians
to recognize whether an article which is not described in New and
Nonofficial Remedies has been omitted because it does not need
admission or because it has been rejected, the Council furnishes the
following more detailed definitions:
OFFICIAL ARTICLES.--_Articles official in the U. S. P. or N. F. do not
require consideration by the Council if they are marketed under the
official name and if no unestablished therapeutic claims are made for
them._
These do not require consideration by the Council, since standards for
them are provided in these books, and enforced under the provisions
of the federal Food and Drugs Act, except that they may be mentioned
for information. Consideration by the Council becomes necessary if a
U. S. P. or N. F. product is offered for sale under a name other than
that, or the synonyms, under which the product is described in one of
these books of standards, or if the proprietors or their agents advance
claims that the product possesses therapeutic properties other than
those commonly accredited to it.
MODIFICATIONS OF U. S. P. AND N. F. PRODUCTS.--A pharmacopeial or
National Formulary product which is marketed under the official title
or synonym, but with well-founded claims that its purity, permanence,
palatability or other physical properties excel the official standard,
may, if no extraordinary therapeutic properties are asserted, be
considered as an official article and held not to be within the scope
of New and Nonofficial Remedies. When such products are marketed under
the claim that they possess therapeutic properties other than those
commonly accredited to the U. S. P. or N. F. products of which they
are modifications, they shall be subject to the consideration of the
Council.
SPECIFICALLY EXEMPTED PREPARATIONS.--Foods, in general, unless marketed
with the claim that they possess therapeutic properties shall not, at
the present time, be considered by the Council. Mechanical appliances,
at the present time, shall not be considered by the Council. Mineral
waters (natural), at the present time, shall not be considered by the
Council. With these exceptions, products which in the judgment of the
Council are manufactured and marketed in conformity to the principles
underlying the rules of the Council may be accepted for N. N. R.
Products which are manufactured and marketed in a manner which does not
conform to the principles underlying the rules of the Council shall not
be accepted for N. N. R. The burden of proof in establishing claims
for therapeutic properties of products considered by the Council shall
lie with the proprietor or, when a foreign made product, with the
agent who markets the product in the United States. To avoid confusion
with nonofficial substances marketed under similar names, the Council
recommends that official substances be prescribed by their official
titles, followed by the abbreviation “U. S. P.” or “N. F.”; thus:
Tinctura Nucis Vomicae, U. S. P.; Elixir Gentianae, N. F.
SUBSTANCES DESCRIBED IN NEW AND NONOFFICIAL REMEDIES.--In the body of
the book will be described simple proprietary substances and their
preparations; proprietary mixtures if they have originality or other
important qualities which, in the judgment of the Council, entitle them
to such place, and important, nonproprietary, unofficial articles.
The Council recommends that when the latter are prescribed, they
be indicated by the abbreviation, “N. N. R.,” thus insuring to the
prescriber the quality of these articles laid down in the book.
PROPRIETARY MIXTURES.--A mixture will be considered as proprietary,
and therefore requiring consideration by the Council for admission
to the book or appendix, if it contains any proprietary article; if
it is marketed under a name which is in any way protected, or if
its manufacturer claims for it any unusual therapeutic qualities.
Proprietary mixtures which are marketed in conformity with the
rules are listed in the appendix of the book under the names of the
respective manufacturers. Such proprietary mixtures are not admitted
to the body of the book, save in the exceptional cases cited in the
preceding paragraph.
NONPROPRIETARY MIXTURES OF OFFICIAL SUBSTANCES.--Since the ingredients
of such mixtures do not require consideration by the Council, and
since the mixtures are not open to the proprietary abuses which call
for the work of the Council, it is not necessary that they should be
investigated by the Council. The physician must judge whether such
mixtures should be directed to be prepared by the pharmacist, or
whether he is justified in ordering a ready-made preparation. If he
decides to use a ready-made, nonproprietary preparation, he must judge
for himself whether it is marketed in accordance with the rules. It
should, however, be remembered that the application of a trade name to
any substance makes it proprietary.
Explanation of Rule 1: Composition
_Secrecy Objectionable._--It is not only the right but also the duty of
the physician to know the essential composition of what he prescribes;
the Council cannot compromise on this proposition.
_Vehicles and Preservatives._--In the case of mixtures, not only the
potent ingredient, but also the general character of the vehicle, the
presence of alcohol, and the identity of preservatives, or of any other
substance, whether added or present as an impurity, must be stated if
these can under any circumstances affect the therapeutic action of
the article. This, as a rule, does not mean the publication of trade
secrets, such as flavors or the details of the working formula.
_Trade Secrets._--Furthermore, trade secrets will not be received as
confidential by the Council, since it accepts information only with
the distinct understanding that this may be freely published, at its
discretion.
_Inspection of Factories._--The Council does not accept invitations to
inspect factories; its concern is with the finished products.
On the other hand, the Council requires that the information be
complete and accurate as to medicinal ingredients.
_Unofficial Constituents._--Unofficial constituents of proprietary
mixtures must be presented by the manufacturer in the regular way and
must be acted on by the Council before the preparations containing them
can be accepted.
_Fraud._--When it appears that a manufacturer has made a _deliberately_
false statement concerning a product, he is asked to furnish an
explanation; and if this is not satisfactory, the product will not be
accepted, even if the false statement is subsequently corrected or
omitted.
_Testimonials._--The foregoing paragraph applies not only to statements
made to the Council, but also to statements furnished to physicians by
the manufacturer or his agents, even when these statements are in the
guise of testimonials.
Explanation of Rule 2: Identification
In order to avoid errors in the case of chemical compounds, and to
guard against adulterations, lack of potency or strength, and the
mistaking of one chemical for another, it is necessary to have at hand
suitable tests.
_Tests, etc._--If these facts have appeared in the literature, or
in standard textbooks, reference to them will be sufficient; but
with new chemicals, especially synthetics, the manufacturer or his
representatives will be required to supply such tests for publication,
as will assure an intelligent opinion of these products.
_Physiologic Standardization._--In cases in which chemical methods of
identification are unknown or unreliable, physiologic standardization
should be employed. The Council considers the phrase “physiologically
standardized” or “assayed” as misleading unless the standard and
method are published in sufficient detail to permit of their control
by independent investigators. It is evident that when no standard is
published, it is impossible to know whether the quality is high or
low, and the conscientious manufacturer who sets for himself a high
standard is placed on a level with the dishonest or careless one who
adopts a low standard. Again, if the process of standardization is
not published, it is impossible to learn, without actual trial, the
relative value of one preparation as compared with that of another
manufacturer, or to confirm or disprove the statements of the
manufacturer as to the quality of his product.
_Standardization of Disinfectants and Germicides._--No disinfectant or
germicide of the phenol type will be accepted for New and Nonofficial
Remedies whose phenol coefficient, determined according to the method
of the Hygienic Laboratory, U. S. P. H. S., is not stated on the label
of the preparation.
Explanation of Rule 3: Direct Advertising
_Lay Advertising._--The impossibility of controlling the irresponsible
claims which are usually made in advertisements to the public, the
well-known dangers of suggesting by descriptions of symptoms to the
minds of the people that they are suffering from the many diseases
described, the dangers of the unconscious and innocent formation of a
drug habit, and the evils of harmful self-medication, including the
dangers of the spread of many infectious and contagious diseases when
hidden from the physician, and similar well-known considerations, are
the reasons for discouraging, in the interest, and for the safety, of
the public, this reprehensible form of exploitation. Advertising in
medical journals, etc., distributed solely to physicians, does not come
within the scope of this rule.
_Exceptions._--In the case of subjects on which the public should be
instructed, as the use of disinfectants, germicides, antiseptics and
foods, advertisements to the public, if not in objectionable forms,
are considered admissible. In no case shall such advertisements
include recommendations for use as curative agents, nor shall the
names of any diseases be mentioned in exploitation. If the preparation
is sufficiently toxic to require caution in its use to prevent
poisoning, this fact shall be stated on the label. On account of the
deplorable results which would follow any abuse of this privilege, the
conscientious cooperation of manufacturers and their agents in adhering
strictly to the limitations laid down is asked; and for the same reason
the acceptance of an article which is so advertised as to infringe on
these limitations in any essential way (as by naming diseases or by
making false and exaggerated claims) shall be summarily rescinded,
and the reasons for such action may be published without notice to
manufacturer or agent. A disinfectant, germicide or antiseptic will
be accepted for description in New and Nonofficial Remedies, and an
article of this class which has already been accepted will continue
to be included in New and Nonofficial Remedies only on the explicit
understanding by the manufacturer and agent that such infringements of
the rule will be followed by deletion of the article and by publication
of the facts as described.
_Foods._--We may divide the foods into three groups. The first group
contains the ordinary foods, including the well-known breakfast
foods. These do not come under the supervision of the Council in
any way. The second group includes a large and important class of
manufactured products, such as invalid and infant foods, which in a
sense stand between the first and third groups. The public has the
same interest in these foods that the physician has, and usually is
supplied with full information concerning them. While the primary
recommendation of these articles should naturally come from the
physician, it cannot be expected that their continued use should
depend on repeated prescriptions. Information concerning this group
of foods would come naturally and properly from a physician, and the
collection and dissemination of this information may very properly be
included in the work of this Council. As the products in this class
are used extensively, it is not proper to limit their advertising
to medical journals, but the advertising should be permitted in the
lay press so long as it is conducted in a manner compatible with
the rules of the Council. The third group includes medicinal foods
proper, such as predigested foods. These have a relatively low food
value and are characterized by a high alcohol or preservative
content. They frequently contain strictly medicinal substances, or
food substances for which distinct therapeutic properties are claimed.
These products should be used only on the advice of the physician, and
the advertisements should be restricted as in the case of ordinary
medicines.
_Advertisements in Foreign Countries._--The Council deals primarily, in
the interest of the public and of the medical profession, with articles
proposed for admission to New and Nonofficial Remedies, and, in
determining the status of any article, must take into consideration any
statements made regarding it or any method of advertising it employed
by the manufacturer or his authorized agents or representatives,
whether in this country or abroad. The Council will not regard as
within its scope, however, questions concerning the marketing of
articles (except the matter of direct advertising to the laity and
unwarranted claims or misrepresentations) in any country which has a
public body corresponding to this Council.
Explanation of Rule 4: Indirect Advertising
_Matter Distributed Solely to Physicians._--It should be remembered
that the sole intent of this rule is to protect the physician, so
that in prescribing a proprietary medicine he shall not unconsciously
advertise proprietary preparations. The rule imposes no restriction on
the legitimate methods of bringing a remedy to the attention of the
profession, such as advertising in medical journals, circulars and
other printed matter distributed solely to physicians. The rule applies
only to the package as it may reach the patient.
_Naming Diseases on Labels._--The naming of diseases on the label
or package is not necessary, as is shown by the very large number
of proprietary products which have been successfully introduced
without resorting to this expedient. This method of popularizing a
proprietary remedy with the laity is most objectionable, and should not
be tolerated in any form. In general, therapeutic indications should
be omitted from the label and package. The Council will not insist
on this point, however, when such indications are so given as not to
promote self-medication, particularly in diseases which require expert
diagnosis and supervision. It will be considered an infringement of
the rule if an article be marketed in bottles which have the name of
the article blown into the glass, or if otherwise the name or initials
or other distinctive mark of the article is permanently stamped on
the container, on the article itself, or is on the stoppers or seals.
Articles which are marketed in any of these ways are not accepted
for New and Nonofficial Remedies. Readily removable labels are not
objectionable, nor is the permanent affixing of the firm’s initials or
name to the trade package if such initials or name is not suggestive of
the article. The Council does not countenance the use of an accepted
article for advertising other articles which have not been accepted by
the Council.
Explanation of Rule 5: False Claims as to Origin
_Source._--No false or misleading statement in regard to an article can
be permitted concerning the source of material from which it is made,
or the persons by whom it is made. Some glaring frauds of this nature
have been perpetrated in the past, and this rule is intended to prevent
such imposition.
Explanation of Rule 6: Unwarranted Therapeutic Claims
_Therapeutic Questions._--This rule insists that the claims of
manufacturers or agents concerning the therapeutic properties of their
products must be compatible with demonstrable facts. Manufacturers
will be held responsible for all statements made or quoted in their
advertising “literature” regarding their products. Recognizing the
existence of honest differences of opinion on many therapeutic
questions, the Council desires to be liberal in the application of
this rule. It is natural that a manufacturer should be partial toward
his own product, and a moderate degree of emphasis in advertising may
not be objectionable. The Council, however, will not admit claims which
are neither in harmony with already accepted facts nor supported by
acceptable evidence. In doubtful cases the Council considers these
questions with the advice and cooperation of its staff of clinical
consultants.
_Clinical Evidence._--To be acceptable, the clinical evidence must
offer objective data with such citation of authority as will enable the
Council to confirm the facts and establish the scientific value of the
conclusions drawn. Clinical data are worthless when the author is not
cited. The facts on which claims with regard to the value of a remedy
are based must have been rendered accessible for investigation and
confirmation by disinterested observers, either through publication or
through the records of a hospital or other institution.
Explanation of Rule 7: Poisonous Substances
_Poisons._--For the information of the pharmacist or dispenser, and to
enable him to safeguard the interests of the patient and the physician,
all articles containing such potent agents as the poisonous alkaloids
and other organic substances and the salts of some of the metals should
have the exact amount of these ingredients which is contained in the
average adult dose stated on the label.
Explanation of Rule 8: Objectionable Names
_“Coined” Names._--Many of the abuses connected with proprietary
medicines arise from “coined” proprietary trade names. Such names will
not be recognized by the Council unless in particular instances the
Council shall deem their use to be in the interest of public welfare.
In every such exception the burden of proof, both for establishing and
for continuing the exception, lies with those who market the product.
_Proprietary (“Trade”) Names When Permitted._--In consideration of
the benefits which may come from the discovery of a therapeutic
agent, the Council concedes to the person or firm which, by right of
discovery, controls such a product the right to name it. The Council
will offer no opposition to an arbitrary name for such a new product,
provided it is not misleading, therapeutically suggestive, or otherwise
subversive of scientific pharmacy and therapeutics. If the discovery
that a previously known substance has therapeutic value is deemed of
sufficient importance, the Council may recognize a name for such a
substance if the name is applied by the person who makes the discovery;
or, with the consent of the discoverer or in the absence of any protest
on his part, the Council may recognize a name applied by the firm which
first makes such a product available to physicians. In the interest
of rational drug therapy, the Council recommends that trade names be
coined so as to indicate the potent element or constituent.
_Scientific Names._--When the proprietary or trade name for an article
is considered insufficiently descriptive of its chemical composition
or pharmaceutical character, the Council may require as a condition
for the acceptance of such articles that a descriptive scientific
name satisfactory to the Council appear on the labels, circulars
and advertisements for such an article. For all definite chemical
substances it is required that the scientific name be given prominence
on the labels, in circulars and advertisements.
_Proprietary Names for Unoriginal Articles._--Proprietary names
will not be recognized for articles which are included in the U. S.
Pharmacopeia or National Formulary or for unessential modifications
of such articles. Neither will proprietary names be recognized for
substances or mixtures which are described in medical or pharmaceutical
publications. In the marketing of unoriginal articles, the legitimate
interests of the producer are fully served by identifying such products
by appending the name or initials of the manufacturer or agent, or
by the use of a general brand mark. No objection will be made by the
Council to the use of such brand marks, provided that in no case shall
such mark be used as a designation for an individual article.
For any product which, by reason of the absence or lapse of patent
rights or for other reasons, is open to manufacture by more than one
firm, the Council reserves the right to select a common name and to
provide standards of identity, purity and strength, and then will
accept such article only if it is marketed under the title adopted as
the N. N. R. name or the name under which such article was introduced
(to which may be appended the firm’s identifying mark).
_N. N. R. to U. S. P._--When an article which has been accepted for
New and Nonofficial Remedies is admitted to the U. S. Pharmacopeia
or National Formulary, it will be omitted from New and Nonofficial
Remedies one year after such standardization if the name of such
article is used in these standards either as the main title for the
product or as a synonym. If the name under which the article is
described in New and Nonofficial Remedies is not used in these books of
standards, the proprietary preparation will be retained provided the
official name is given prominence on the labels and in the circulars
and advertisements of such article. When the Council adopts a common
name for an article that has been admitted under another name, it
will be continued under the older name only on condition that the
Council name be given prominence on the label and in the circulars and
advertisements for such article.
_Pharmaceutical Preparations and Mixtures._--These, with rare
exceptions, are not original in composition and there is seldom
any reason why they should be endowed with arbitrary names. On the
contrary, it is important that the prescriber should be reminded
constantly of their potent ingredients.
_Therapeutically Suggestive Names._--Articles bearing therapeutically
suggestive names will not be accepted for New and Nonofficial Remedies,
first, because they are likely to lead physicians into prescribing
names instead of remedies, and second, because they tend to encourage
unwarranted self-medication by the laity. Even if the name is at
first apparently meaningless to the public, its meaning will soon be
understood because patients soon learn the technical names applied to
their diseases and symptoms. The prohibition against therapeutically
suggestive names is not applied to serums, vaccines and antitoxins,
because the accepted nomenclature of the specific organisms used in
their preparation makes this unavoidable and because self-medication
with them is improbable.
Explanation of Rule 9: Patents, Trademarks, Copyrights, Etc.
_Protection._--This information is important as a means of determining
the legal status of medicinal articles and as an aid to their ready
recognition in current publications.
Explanation of Rule 10: Unscientific and Useless Articles
_Unscientific Compounds._--The use of articles which are unessential
modifications of official or established nonproprietary articles is
unscientific and serves no useful purpose. The Council will not accept
products which are scientifically unsound and which, therefore, must
be considered useless or inimical to the best interest of the medical
profession and the public. This class includes compounds or mixtures
containing an excessive number of active ingredients; those compounds
or mixtures the components of which are of no probable assistance to
one another, and those articles which are of no therapeutic value.
_Unessential Modifications of Official Substances._--The subterfuge
of obtaining proprietary rights over an official or established
nonproprietary product, by introducing unessential modifications, also
tends to confusion and abuses, and such articles will not be admitted
by the Council. Essential and important modifications, however, will
receive recognition. (The Council interprets the term “established
nonproprietary product” as applying to a preparation of any formula
which has been published through any recognized or reasonably
accessible channel of publication, prior to its appropriation or
modification by a manufacturer.) Duplicates of biologic products
accepted under the name of the manufacturers will not be accepted under
the names of the distributors.
THE COUNCIL ON PHARMACY AND CHEMISTRY, PRESENT AND FUTURE[A]
W. A. Puckner, Phar.D.
Secretary, Council on Pharmacy and Chemistry
[A] Read before the Chicago Medical Society, March 26, 1919.
The World War marked an epoch in the existence of the Council on
Pharmacy and Chemistry, as it did in all human endeavors. The
information and experience which had been accumulated by the Council
during its thirteen years’ existence was drawn on by our government,
directly or indirectly, and it also received consideration in England,
France,[1] Belgium, Holland,[2] Italy,[3] Sweden and elsewhere. In the
world wide readjustment that has begun, the efforts of the Council,
past and present, will influence the plans of those who engage in
the manufacture or sale of medicines, and, undoubtedly, will be the
incentive to the establishment of similar bodies in other countries.
[1] “New and Nonofficial Remedies” in France, Foreign News, J. A. M. A.
=71=:1331 (Oct. 19) 1918; =70=:1783 (June 8) 1918.
[2] Nederl. Tjdschr. v. Geneesk. Oct. 5, 1918, p. 1201.
[3] An Italian View of the Proprietary Evil, Foreign News, J. A. M. A.
=71=:840 (Sept. 7) 1918; The Council on Pharmacy and Chemistry and the
Patriotic Medical League in Italy, ibid. =71=:918 (Sept. 14) 1918.
As secretary of the Council almost from the time of its organization
in 1905,[4] and knowing the work of its members and its collaborators,
I am firmly convinced that this body has deserved the endorsement and
support given it by the American medical profession. I welcome this
opportunity to present an outline of the Council’s past activities and
to speak of some of the problems of the future, because I feel assured
that a knowledge of its endeavor to improve drug therapy will increase
the profession’s confidence in the Council and add to the number of its
supporters.
[4] Although the Council on Pharmacy and Chemistry was established in
1905, it is likely that only a small percentage of physicians know
just what the Council is, or have any conception as to its personnel
and its ability to judge the available evidence for proprietary
medicaments. The personnel has changed from time to time since 1905.
At present its membership is: C. L. Alsberg, A.M., M.D., chief of the
Bureau of Chemistry, U. S. Department of Agriculture, Washington,
D. C.; R. A. Hatcher, Ph.G., M.D., professor of pharmacology, Cornell
University Medical College, New York City; A. W. Hewlett, M.D.,
professor of medicine, Leland Stanford Junior University Medical
School, San Francisco; John Howland, M.D., professor of pediatrics,
Johns Hopkins University Department of Medicine, Baltimore; Reid
Hunt, M.D., professor of pharmacology, Harvard University Medical
School, Boston; Henry Kraemer, Ph.D., professor of pharmacognosy,
University of Michigan College of Pharmacy, Ann Arbor, Mich.; W. T.
Longcope, A.B., M.D., Bard Professor of the Practice of Medicine,
College of Physicians and Surgeons of Columbia University, New York
City; G. W. McCoy, M.D., director of the Hygienic Laboratory, United
States Public Health Service, Washington, D. C.; Lafayette B. Mendel,
Ph.D., Sc.D., professor of physiologic chemistry, Sheffield Scientific
School, Yale University, New Haven, Conn.; F. G. Novy, M.D., Sc.D.,
professor of bacteriology, University of Michigan, Ann Arbor, Mich.;
W. W. Palmer, B.S., M.D., associate professor of medicine, College of
Physicians and Surgeons of Columbia University, New York City; L. G.
Rowntree, M.D., professor of medicine, University of Minnesota Medical
School, Minneapolis; Torald Sollmann, M.D., professor of pharmacology
and materia medica, Medical Department, Western Reserve University,
Cleveland; Julius Stieglitz, Ph.D., Sc.D., Chem.D., vice chairman of
the Council, professor of chemistry, University of Chicago, Chicago;
G. H. Simmons, M.D., LL.D., chairman of the Council, editor of The
Journal of the American Medical Association, Chicago, and W. A.
Puckner, Phar.D., secretary of the Council, director of the Chemical
Laboratory of the American Medical Association, Chicago.
THE COUNCIL’S ACTIVITIES
Organized primarily for the purpose of putting a stop to false
declarations with regard to the composition of proprietary medicines,
the Council’s activities have broadened until its work may be
characterized as “a propaganda for the rational use of drugs.” The
following are some of its activities:
1. _New and Nonofficial Remedies._--This is an annual volume, issued
by the Council. It describes both proprietary and nonofficial,
nonproprietary drugs which are deemed worthy of consideration by the
medical profession. To be admitted to this book, a preparation must
comply with certain definite rules which stipulate, in effect, that its
composition be declared, that no untrue or grossly exaggerated claims
be made for it, and that it shall give promise of having therapeutic
value.
With the exception of a few which are still under consideration, the
Council has considered all proprietaries whose owners or accredited
agents have requested that an examination of the products be made,
and it has admitted to the book those which were found eligible. In
addition, the Council has examined all of the more important or widely
exploited proprietaries, even when no examination was requested,
and it has admitted those of this group which were found eligible.
Further, the Council has admitted to the book certain nonofficial,
nonproprietary articles which seemed to give promise of therapeutic
usefulness, and it has established standards for the control of their
identity and purity, and listed those brands which complied with these
standards.
As most proprietary medicines are of a more or less experimental
nature, they are accepted for inclusion in New and Nonofficial Remedies
only for a limited time--usually a period of three years. At the
expiration of the period of acceptance, each preparation is reexamined
and retained only if the claims made for it and the present day
knowledge of its value permit this action.
Since manufacturers give information only in regard to their own
products, New and Nonofficial Remedies groups together articles of a
similar character, and includes in each case a general discussion of
the group for the purpose of comparison, not only with each other, but
also with the established or pharmacopeial drugs which members of the
group are intended to supplant.
In brief, New and Nonofficial Remedies is a book in which are described
preparations that have been accepted by the Council. The description
includes facts that the physician should have. It is a book that should
be in the hands of every physician who prescribes medicines, and who
wishes to know the facts regarding the newest remedies. It is the only
book in which he can find information relative to proprietary medicines
that are worthy of his patronage. It will protect the physician who
makes use of it against the wiles of the promoters of products not
worthy of his patronage. It would certainly be of use to the physician
when the detail man calls on him, for if he were being importuned to
prescribe or use samples of something which he had not heretofore used
and which he was unable to find in N. N. R., he might ask the detail
man why. In the nature of things few physicians are sufficiently expert
in chemistry and allied sciences to be able unerringly to discriminate
between the true and the false as regards many preparations that he is
asked to prescribe.
2. _The Reports of the Council on Pharmacy and Chemistry._--A
medicament may be inadmissible to New and Nonofficial Remedies for
various reasons; it may be worthless or irrational, its composition
may be secret or indefinite, or it may be exploited under exaggerated
or unwarranted claims or in a way otherwise detrimental to the public
health and scientific medicine. Of these various reasons which make
an article unacceptable, the manufacturer obviously may remove all
except the first, viz., worthlessness or irrationality. Consequently,
a preparation which has been presented for admission is not definitely
rejected until after its proprietor has been informed of the objections
to his product and has failed to bring the preparation in conformity
with the Council’s rules. When a preparation is found definitely
inadmissible to New and Nonofficial Remedies, that is, when the
proprietor cannot or will not make it acceptable, the Council prepares
a report for publication. These reports are sent for publication to The
Journal of the American Medical Association, and later published in the
annual “Reports of the Council on Pharmacy and Chemistry.” The more
important of these are also published in the book, “The Propaganda for
Reform in Proprietary Medicines.”
3. _Useful Drugs._--Since the domination of proprietary medicines,
which was retarding medical advance and threatening therapeutic chaos,
had been made possible only by the insufficient and inefficient
instruction given in medical schools in subjects having to do with
drugs, the Council appointed a Committee on Medical Teaching to secure
the cooperation of teachers in materia medica, pharmacology and related
branches. This committee has endeavored to effect an improvement in
these courses of instruction. One of the results of this work was the
selection of a list of drugs to serve as a basis of materia medica
instruction and thus insure that medical students shall be better
informed with regard to the therapeutic worth of a few well established
drugs, rather than, as in the past, leaving school with a smattering
of knowledge about many drugs. The outcome of these efforts is the
publication of “Useful Drugs,” a concise but thorough and up-to-date
discussion of the actions, uses and dosage of the more important
drugs. The list of drugs presented in this book is now the basis of
instruction in many schools; and many state examining boards are
confining their materia medica questions to the drugs in the list.
4. _Epitome of the U. S. P. and N. F._--To encourage the use of
official drugs and to make available an estimate of their therapeutic
value, a committee of the Council prepared an abstract of the U. S.
Pharmacopeia and the National Formulary. This booklet, the “Epitome of
the U. S. Pharmacopeia and National Formulary,” presents those portions
of these books which are of interest to physicians, and in addition,
gives a concise statement of the therapeutic usefulness of the drugs
and preparations described in them.
5. _Patent Law Reform._--Some of the worst abuses connected with the
exploitation of proprietary medicines have been made possible by our
patent and trademark laws and the method of their interpretation and
enforcement. The Council, therefore, appointed a committee to study
these laws and the various propositions advanced for their improvement.
This committee has published, from time to time, reports on various
phases of our patent and trademark laws and recently summarized these
reports in an address[5] sent to the commissioner of patents and the
interested congressional committees. It is hoped that by means of these
reports physicians will be enabled to give intelligent support to a
revision of the patent and trademark laws when legislation is proposed.
[5] Need for Patent Law Revision, A. M. A. Council on Pharmacy and
Chemistry Reports, 1917, p. 130.
6. _Therapeutic Research._--Through its Committee on Therapeutic
Research, and with the aid of funds provided by the Board of Trustees
of the American Medical Association, the Council has encouraged the
investigations of questions which might lead to a better understanding
of the action of drugs. These investigations are brought together in
the annual reports of the Committee on Therapeutic Research, and are an
important addition to our knowledge of drug action.
In the past, the Council has in particular encouraged the investigation
of the action and therapeutic value of widely used drugs regarding
which our knowledge is still unsatisfactory. These investigations
have included a study of the action of strychnin in cardiac disease,
a comparison of the action of absorption and excretion of iodid
preparations, a study of the pharmacology of the opium alkaloids,
etc. Appreciating that the available knowledge of proprietary drugs
is one sided in that it comes from investigations made by interested
pharmaceutical concerns or from investigations made at the instigation
of these firms, the Council is planning a comprehensive study of many
of the synthetic drugs that have gained some vogue during recent years.
THE FUTURE
Medical research, and efficient instruction in therapeutics and related
subjects, spell a diminishing influence of commercial medicine over
rational therapeutics. The fact that the present shortage of German
synthetics has not handicapped seriously the practice of medicine
should be a lesson to American physicians for many years to come.
On the other hand, it must be remembered that the publicity given to
the reports of the Council and to other contributions toward rational
therapeutics by The Journal of the American Medical Association,
the journals of the state organizations, and a few personally owned
publications, is as nothing when compared with the persistent and wide
publicity given to the propaganda of the proprietary houses. While a
report setting forth the objections to a proprietary is published but
once, the firm’s laudatory pronouncement goes forth again and again
until the Council’s report is completely overwhelmed and forgotten.
Manufacturers of proprietaries not only keep in close touch with the
practicing physician by means of house organs, special “literature,”
or by traveling representatives, but many of the firms, through the
meritorious lines of pills, tablets, tinctures, etc., which they put
out, also obtain and hold the good will and confidence of a large
proportion of the medical profession.
Furthermore, some of these firms may gain the confidence of the medical
profession through these high grade pharmaceuticals, and certain of
their proprietaries may be of distinct therapeutic value but may fail
to be acceptable for New and Nonofficial Remedies, because they do not
conform to the reasonable rules of the Council. These firms do not
find it profitable to force the sale of their regular nonproprietary
pharmaceuticals by unwarranted claims or objectionable methods, yet
they may consider it good business to market certain proprietary
products by means of claims which are extravagant and without warrant,
and which will lead to indiscriminate use by the profession and the
public. In a word, where there is one dollar spent on behalf of
rational medicine, thousands are spent for the purpose of increasing
the sale of preparations which directly or indirectly are a detriment
to the public health, to medicine, and to the pocketbook.
That the day of the secret nostrum of the pseudo-chemical company is
not yet past is well illustrated by the recent introduction of an
asserted arsphenamin preparation called “Syphilodol.” The A. M. A.
Chemical Laboratory proved one form of this asserted French discovery
to be essentially a pill of mercurous iodid. Another form of Syphilodol
(for intravenous administration) had all the characteristics of water,
and appeared devoid of any potent ingredient. Though the advertising
sent out by the promoters in regard to its composition was suspiciously
evasive, the _Illinois Medical Journal_ published an advertisement
of “Syphilodol,” which, possibly by a coincidence, appeared above an
appeal to “Our Readers” to use wares advertised in that journal.
While such rank deceptions as “Syphilodol” are not common, there are
more subtle deceptions that are even more dangerous. Types of widely
exploited remedies of today comprise so-called ethical specialties
composed of well known and established drugs (with “jokers” hidden
away somewhere) or preparations which have a plausibly fascinating
pseudo-scientific background of radiant energy, colloidal chemistry,
nonspecific protein reaction, or something of the sort. The latter
class of preparations in particular appeal to physicians who are
striving hard to keep pace with modern science. Exposure of their
fallacies requires most careful consideration on the part of the
Council.
Progress toward a rational and scientific drug therapy must continue,
and, therefore, it is important that the Council on Pharmacy and
Chemistry should continue to make the investigation of proprietary
medicines its chief work. Investigation of a proprietary medicine,
however, and a report of such investigation are of value in direct
ratio only to the number of physicians who read the report, endorse
it and act in accordance with its conclusions. In order that you may
determine to what extent those preparations which are admitted to New
and Nonofficial Remedies deserve your interest and confidence, it will
be worth while briefly to outline the rules which govern the Council in
the admission of articles to New and Nonofficial Remedies.
RULES GOVERNING THE ACCEPTANCE OF ARTICLES FOR N. N. R.
_Composition._--Rules 1 and 2, and in a measure 5, 7, and 9, deal with
the composition of articles. Rule 1 requires that the quantitative
composition of an article be furnished the Council for publication.
Rule 2 requires that the manufacturer furnish methods whereby the
composition of products that are definite chemicals or the potent
constituents of mixtures may be determined. The Council does not
require that the process of manufacture of an article be declared
unless this becomes necessary in order to judge its composition. Rule
5 requires that statements with regard to the origin and source of an
article shall be truthful. Rule 7 requires that for the guidance of the
dispenser, the amounts of poisonous ingredients of a preparation be
placed on the label. Rule 9 requires that if patent rights are claimed
for a product, the Council be informed on this point.
That it is not only the right but also the duty of the physician to
know the composition of what he prescribes for his patients is so
generally admitted that few have attempted to market preparations of
avowedly secret composition. When the Council first began its work,
it was common to see chemical formulas or statements of composition
published which a chemist or a pharmacist was able to pronounce
at a glance as impossible.[6] It was not unusual to find that the
promoter published “a formula” for his preparation, rather than “the
formula.”[7] Today, however, a more prudent, if not more honest, course
is pursued. This gives a “formula” which is correct so far as it goes,
but which fails to divulge the actual composition of a preparation.
When it is considered that many physicians are not any too conversant
with the chemistry and pharmacy of drugs, it is not surprising that
some administered the proprietary “Venarsen,” regarding the composition
of which they had only the vague statement that it was “... a
comparatively nontoxic organic arsenic compound, 0.6 gm. representing
247 mg. (3-3/4 grains) of metallic arsenic in chemical combination
...” in the belief that a preparation similar to that first introduced
as salvarsan was being used. That “Venarsen” contained its arsenic as
sodium cacodylate--a notoriously inactive state of combination--does
not justify the intravenous administration of a drug of unknown
composition.
[6] Puckner, W. A.: The Abuse of Chemical Formulas, Reports A. M. A.
Chemical Laboratory =3=:7, 1910.
[7] The Formula for Glyco-Thymoline, J. A. M. A. =52=:147 (Jan. 9) 1909.
While for the present it probably is not feasible to require, on the
part of those who manufacture medicinal preparations, such professional
training as is required of those who prescribe and those who dispense
them, it certainly is not too much to require, as does Rule 2, that a
manufacturer shall be able to demonstrate that his preparation has the
composition claimed for it. Nor is it sufficient for him to know that
the ingredients claimed as constituents were used in the manufacture.
The fallacy of his method of reasoning was furnished by the physician
who reported that he had personally added the required amount of
mercuric iodid for a batch of “Mercol” which, nevertheless, was devoid
of mercury.[8] Acceptance of this rule by manufacturers will permit
physicians to have a more accurate knowledge of the composition of
preparations such as “Taka-Diastase”[9] and “Iodeol”.[10]
[8] Hunt, Reid, and Seidell, Atherton: Howell’s Mercol, J. A. M. A.
=52=:225 (Jan. 16) 1909. Howell’s Mercol Again: Another Analysis Fails
to Reveal the Presence of Mercury, J. A. M. A. =52=:1595 (May 15) 1909.
[9] Taka-Diastase and Liquid Taka-Diastase: Report of the Council on
Pharmacy and Chemistry, J. A. M. A. =59=:50 (July 6) 1912.
[10] Iodeol and Iodagol: Report of the Council on Pharmacy and
Chemistry, J. A. M. A. =69=:1725 (Nov. 17) 1917.
A requirement similar to that of Rule 5 is contained in the Federal
Food and Drugs Act and so no objection has been made to this rule which
requires a truthful statement of the origin and source of articles. An
illustration for the need of the rule was furnished by the one time
popular “Vin Mariani”[11] which, though very French in its makeup,
was found to be largely of the “made in the United States” variety of
tipple.
[11] Vin Mariani: Official Report of Council on Pharmacy and
Chemistry--With Comments, J. A. M. A. =47=:1751 (Nov. 24) 1906.
The issuance of a patent for a medicinal product does not prove that
such a product presents a discovery or that its owner is entitled to
a temporary monopoly, yet it is only fair to physicians and to other
manufacturers that notice of such patent claims be given. Hence, the
Council publishes in New and Nonofficial Remedies the information
bearing on this point.
_Lay Advertising._--Rules 3 and 4 provide against the recognition of
articles that are advertised to the public directly or indirectly,
exempting from this requirement preparations which the Council believes
are safe to be so advertised.
It has been held with some justice that certain shotgun proprietaries
are purchased by the public with as much circumspection as they are
ordered by those physicians who are addicted to the prescribing of
them; but even the exploiters of these mixtures have not denied that
the use of medicines by the public on its own initiative is surrounded
with many objections. Hence the practice of self medication should not
be encouraged by prescribing or using those preparations advertised for
public use.
The only objection to the rule has come from a firm which markets a
brand of liquid petrolatum, the Standard Oil Company of Indiana. The
Council has considered the question of exempting simple laxatives from
the restrictions of Rules 3 and 4 as it has exempted antiseptics and
nonmedicinal foods. The conclusion was, however, that the excessive
use of a simple laxative like a liquid petrolatum, when prompted by
newspaper exploitation, is likely to be detrimental to health by
overuse as well as by misuse.
The indirect advertisement to the public, which Rule 4 provides
against, has been the means of inducing the extensive lay use of
“Antikamnia,” “Bromidia” and “Fellows’ Syrup.” Naturally Rule 4 has
been bitterly opposed by most proprietary firms. Arguing that many
physicians dispense their own drugs, pharmaceutical firms have insisted
that every medicinal preparation should bear on its label, not only
the dose of the preparation, but also a statement of the diseases in
which the article is indicated. Whether manufacturers anticipated the
profession’s resentment toward the claim that physicians determine
the treatment and perhaps the diagnosis by means of the statements on
labels, or because the Shirley amendment to the Food and Drugs Act
makes the proprietor responsible for therapeutic claims on the label
of a medicine, it is a fact that fewer preparations than formerly need
to be refused on account of infringement on this rule. In fact, some
thoroughly objectionable proprietaries make a show of being “ethical”
by omitting all therapeutic discussion from the labels of their
preparations.
_Therapeutic Claims._--Rule 6 makes ineligible for New and Nonofficial
Remedies any articles regarding which the manufacturer or his
agents make unwarranted, exaggerated or misleading statements as to
the therapeutic value. Recognizing the long established custom of
therapeutic exaggeration, it has been most difficult to determine
the degree of conservatism which might with fairness be required
of a manufacturer. In view of the common acceptance of individual
impressions as dependable evidence, it is often almost embarrassing
to declare as incompetent the statement of some well meaning and
all-too-kind-hearted doctor. However, as the pitfalls of haphazard
clinical trials become better known and the physician’s mistrust of
glowing accounts of marvelous cures more outspoken, the manufacturers’
claims will be more moderate.
_Nomenclature._--Were it possible to enact and enforce a law which
would oblige manufacturers to sell their medicinal products under
properly descriptive names and which would make it illegal for a
physician to prescribe it unless he understood the meaning of such
properly descriptive titles, then the Council might safely disband. In
that case, physicians would discontinue the use of most proprietary
preparations in favor of established drugs, and successful newcomers
might each year be counted on the fingers of one hand. Such a rational
nomenclature is not to be thought of, at least in our generation.
Rule 8 requires that the name of an article shall not be misleading,
that it shall not be therapeutically suggestive, and that established
drugs shall not be disguised by fanciful titles. It recognizes the
right of discoverers of new drugs to name their discoveries, and
interposes no objection to arbitrary names for such products so long
as such names are not misleading or do not suggest the therapeutic
uses of the products. As the rule provides against the recognition of
coined names for established nonproprietary drugs, so it requires that
mixtures of drugs shall bear names descriptive of their composition.
It would be a long step forward if physicians would recognize more
fully the objections to the many proprietaries which have, as their
only point of originality, a non-descriptive name for an old drug or
a mixture of well known drugs. It is an encouraging sign that the
Federal Trade Commission, when issuing licenses for the manufacture of
synthetic drugs introduced under German patents, stipulated that all
manufacturers authorized to make a given drug shall use the same name
for it.
_Irrational Articles._--Rule 10 provides against the recognition of
an article which, because of its composition, is useless or inimical
to the best interests of the public and medical profession. This
rule excludes medicaments which (1) are unessential modifications of
established articles, or (2) are of no therapeutic value or (3) are
irrational. With regard to the recognition of mixtures or compounds
containing two or more active ingredients, the Council requires that
the manufacturer establish the rationality of its combination. The rule
has prevented the recognition of many unnecessary so-called ethical
specialties. Though a mass of testimonials was often to be had for
them, these contained no evidence that the mixture was superior to its
potent ingredient, or that its therapeutic effect had been determined.
That there is a healthy tendency to use single drugs for their definite
action and to discard combinations (be they shotgun proprietaries or
“mixed” vaccines) is perhaps best illustrated by the fact that at
the last revision of the U. S. Pharmacopeia a considerable number of
complex antiquities were omitted from that book.
Feeling confident that this meets with the endorsement of the
profession, the Council is examining more critically the evidence for
the value of pharmaceutical mixtures.--(_From The Journal A. M. A., May
10, 1919._)
“ACCEPTED BY THE COUNCIL ON PHARMACY AND CHEMISTRY”
Under the caption given above, the _Journal of the Missouri State
Medical Association_, in its July issue, speaks editorially as follows:
The Council on Pharmacy and Chemistry of the American Medical
Association is a department of our national organization that has
not received the plaudits and encomiums of a wildly joyous medical
profession nor the grateful praises of the enthusiastic manufacturer
of pharmaceuticals. The Council seems indeed to be the unloved child
of the entire family of subsidiary bodies of the association. Perhaps
the reason for this may be found in the character of its duties, for
the Council must expose fraud, sometimes in high places, and protect
the physician from being duped by avaricious persons and by persons
who are themselves sometimes the victims of their own credulity. It
thus happens that the sale of some proprietary article previously held
in high esteem by the practitioner proves valueless, perhaps even
fraudulent. The practitioner, however, may have credited much of his
success in treating certain conditions to that preparation and the
maker has had success in accumulating dollars from its sale and both
parties emit a loud and vicious roar against the Council, because
they both lose money. Nobody wants to be “protected” against making
money--make it honestly, if possible, but make it--but this black sheep
among the Councils of the American Medical Association insists on their
making their money honestly!
Despite many obstacles thrown into its path, the Council on Pharmacy
and Chemistry has serenely pursued its allotted tasks, corrected
its mistakes, improved its methods, and today stands as the only
medium to which the honest physician may turn for information--not
misinformation--regarding proprietary articles. During the war the
Council and the chemical laboratory were in close cooperation with
the Surgeon-General’s Office, testing and investigating every article
offered to the government for the treatment of sick soldiers. The
variety and the number of fakish and fraudulent stuff offered to the
Surgeon-General was a pitiable exhibit of the mental gymnastics of
some people. Just now the Council and the laboratory have a new and
important field before them, i. e., to protect the physicians against
worthless and useless serums, vaccines and synthetics. It will be the
Council’s unpleasant duty to expose the fraudulent and useless among
these articles and stamp truth on those found worthy.
We seem to have wandered from the topic in our caption, but not so in
reality, because the burden of our thought is to lend our influence to
the spread of the motto of the Advertising Clubs of the World, namely,
“Truth in Advertising.” It is our purpose to stimulate a larger degree
of enthusiasm for the work of the Council on Pharmacy and Chemistry
and the Chemical Laboratory, a more generous flow of inquiries
concerning articles unfamiliar to the physician, and particularly to
urge that the words “Accepted by the Council on Pharmacy and Chemistry
of the American Medical Association” be printed on the label and on
all advertising circulars of proprietary articles that have been
admitted to New and Nonofficial Remedies. Then, when pamphlets and
circulars are received by physicians they will read the statements of
manufacturers with sympathetic understanding and with full confidence
in the verity of the declarations. The importance of creating just
that sort of receptivity in the mind of the prospective buyer is so
well known to the astute publicity expert that it is needless for
us to dwell on its advantages. Every proprietary article advertised
in our journal, in The Journal of the American Medical Association,
and in the other state association journals, as well as in several
well-edited privately owned journals, does in effect say to the reader
that the articles so advertised are accepted by the Council because
only proprietary articles so accepted are accepted by us. The fact is
further acknowledged when these firms are permitted to exhibit their
goods at our annual sessions for again the rule is enforced that only
proprietary articles which have been approved by the Council may be
placed on display.
Why not complete the circle of ideas--it would not be a “vicious
circle”--by printing on labels, in advertisements and circulars, the
words: “Accepted by the Council on Pharmacy and Chemistry”?--(_From The
Journal A. M. A., Aug. 2, 1919._)
HELPING THE COUNCIL
If they were built that way, the members of the Council on Pharmacy and
Chemistry of the American Medical Association might become discouraged
at the apparent indifference of many members of the medical profession
to their efforts. There are many physicians who, while figuratively
patting the Council on the back, actually do nothing to aid its
efforts. On the other hand, there are men in the profession who give
the Council active support instead of merely passive appreciation.
The letter that follows was written by such a man to a pharmaceutical
concern:
I am receiving circular advertising from you concerning ---- ----
solution, and I am writing to suggest that until these products
have been approved by the Council on Pharmacy and Chemistry of
the American Medical Association, you are wasting your postage
on the practice. Aside from the fact that these products do not
appeal to me personally, I feel that I am not in a position to
judge the value of such products and I depend entirely on the large
clinical opportunities of the Council on Pharmacy and Chemistry of
the American Medical Association in addition to their laboratory
facilities, in such matters as these. I may, therefore, with all
due respect, suggest that ... it will pay you to eliminate my name
from your mailing list.
The members of the Council on Pharmacy and Chemistry are working week
in and week out without remuneration. Few appreciate how much these
scientific men are doing for rational therapeutics; fewer still realize
how much has been accomplished through their efforts, or how much more
could be accomplished if every physician who at least believes in the
work of the Council would give it his full support.--(_Editorial from
The Journal A. M. A., Nov. 6, 1920._)
DELAYS IN PASSING ON PRODUCTS
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
The Council frequently receives inquiries--some of them accompanied by
expressions of impatience--concerning articles, reports on which appear
to be delayed. It therefore seems advisable to make a statement of some
of the factors which enter into this problem.
The Council fully realizes the importance of giving prompt information
to the profession with regard to proprietary medicines under
consideration. It therefore acts as soon as sufficient information
is available to justify a definite judgment, and publishes its
conclusions as soon as possible. When adequate information is available
at the outset, there is no delay in the publication of the Council’s
conclusions.
Unfortunately, but very naturally, there are many cases in which the
information available at the time the product is submitted is not
sufficient to justify the Council in coming to definite conclusions for
or against the preparation. In some cases the manufacturer possesses
the required information, but to obtain it from him takes time; in
other cases the manufacturer does not possess the information--perhaps
he did not realize the inadequacy of his evidence until the subject was
brought to his attention by the Council.
Such cases might be dealt with in either one of two ways: The Council
might at once reject the article because the claims for it are not
supported by adequate evidence; or, the Council might suspend judgment
and give the manufacturer an opportunity to supply the information.
The first method--immediate rejection--would obviously be felt by
manufacturers as a hardship. To afford the fullest possible opportunity
for the presentation of the case, the Council follows the second
method; that is, it suspends judgment and withholds publication of
a report until reasonable time has been afforded for furnishing the
required information, provided the manufacturer or agent appears to
be making honest and diligent efforts to supply it. The collection
and compilation of such information is sometimes a lengthy process,
especially when the products are of foreign manufacture.
Although it would be easier for the Council to render an immediate
decision than to assist manufacturers to supply the data necessary for
the formation of an authoritative judgment, the Council cannot yield to
importunities for hasty action. It must rely on the medical profession
to bear in mind that the character of a product under consideration
by the Council has not yet been determined. The Council holds that,
during this stage, a product is suitable, at most, for experimental
use.--(_From Reports of Council on Pharmacy and Chemistry, 1915,
p. 119._)
COOPERATION OF THE PHARMACEUTICAL HOUSES
Report of the Council on Pharmacy and Chemistry
In reply to the suggestion made last year by President Bevan that there
should be closer cooperation between the large pharmaceutical houses
and the Council on Pharmacy and Chemistry, the Council submitted to the
Board of Trustees of the American Medical Association the statement
which appears below:
“COOPERATION OF THE PHARMACEUTICAL HOUSES: At the opening meeting
of the House of Delegates last year, President Arthur Dean Bevan
suggested the desirability of greater cooperation between the large
pharmaceutical houses and the Council on Pharmacy and Chemistry. The
need of such cooperation has been recognized by the Council from the
first. In no one direction has the Council made greater effort than
in its endeavor to secure the fullest cooperation of the various
pharmaceutical houses. The difficulty has been, and always must
be, the fundamental antagonism between objectives that are largely
commercial on the one hand and purely scientific on the other.
Nevertheless, the Council has always believed--and has acted on the
belief--that there is a possible middle ground wherein the interests
of therapeutics would not be injured but would go hand in hand with a
commercial development based on enlightened self-interest.
“The profits to be made by a pharmaceutical house from the sale of a
staple drug--a pharmacopeial, National Formulary, or nonproprietary
preparation--which enters into free competition with other drugs
of the same kind, are moderate; the profits to be made from the
sale of a proprietary medicine on which the manufacturer holds a
monopoly are usually large--sometimes enormous. There are, broadly,
two kinds of proprietary preparations advertised to physicians:
One represents laborious research ending in the production of
a new medicinal chemical; this product can be patented and the
manufacturer can obtain a seventeen-year monopoly on its manufacture
and sale. The other represents no research but comprises simple
mixtures--frequently of the “shotgun” variety--of well known
pharmaceuticals, or biologic products sold under trade names. As
these do not represent anything new or original the manufacturer is
unable to obtain a patent, but by means of the trade name he can and
does obtain a perpetual monopoly. This, from a business standpoint,
is more valuable than the limited monopoly granted by a patent. It is
not surprising that proprietary remedies of the latter type flourish
so long as physicians unthinkingly accept and prescribe them solely
on the manufacturer’s valuation.
“The Council has practically the undivided support of
manufacturers of medicinal chemicals; that is, of proprietaries
of the first mentioned type. But pharmaceutical firms which
have found it profitable to promote proprietaries of the second
type--“specialties,” unscientific or ordinary mixtures of
pharmaceuticals or biologic products sold under trade names--have not
supported the Council.
“When the Council was organized, it was hoped and believed that all
the large pharmaceutical houses would find it possible and desirable,
if not actually more profitable, to shape their business methods so
as to make their proprietary and other articles conform to those
conservative standards on which the Council bases its rules, and thus
render such articles acceptable for New and Nonofficial Remedies.
It soon developed, however, that the methods of the pseudochemical
companies, whose sales propaganda in the interest of unscientific
nostrums with its attending damage to scientific medicine had led to
the establishment of the Council, had found their lodgment in most
of the pharmaceutical houses. It was a genuine disappointment to the
Council to find that some of the large and old-established firms
were not only unwilling to cooperate with the Council, but in many
instances exhibited a definite antagonism to the Council’s work.
“The object--and duty--of the officers of pharmaceutical houses is
primarily to pay dividends to their stockholders. Through skilful
advertising or the persuasiveness of “detail men,” they are able
to induce physicians to prescribe their controlled products, on
which there are large profits, even though such products have not
only not been accepted by the Council, but in many instances, have
been disapproved. Is it any wonder that concerns which put out such
products are indifferent or openly antagonistic to the work of the
Council? The matter is largely one of business policy. When the
medical profession as a unit will support the Council in its work,
then such firms will find it good business policy to accede to Dr.
Bevan’s suggestion--but not before.”
Evidently the problem resolves itself into this: The Council,
constituted of scientific men, working without remuneration in
the interest of scientific medicine and the medical profession,
expects--and rightfully--the cooperation and support of the members of
that profession. What is needed, therefore, is the active, sympathetic
cooperation of physicians; the cooperation of pharmaceutical houses
will follow as a matter of course. (_J. A. M. A._ =74=:1235 [May 1]
1920.)
The following is the recommendation of the Reference Committee to
which the Report of the Board of Trustees was referred: “A perusal
of the Trustees’ Report, ‘Cooperation of the Pharmaceutical Houses’,
is well worth the time of every member of the profession, and your
committee would emphasize the statement of the Trustees: ‘The
Council, constituted of scientific men, working without remuneration
in the interest of scientific medicine and the medical profession
expects--and rightfully--the cooperation and support of the members of
that profession. What is needed, therefore, is the active sympathetic
cooperation of physicians; the cooperation of pharmaceutical houses
will follow as a matter of course.’
“Your committee would go still further and move that a vote of thanks
of the House be extended to those scientific men who have devoted so
much valuable time to the welfare of the Association.”
(_J. A. M. A._, =74=:1322 [May 8] 1920; _from Reports of Council on
Pharmacy and Chemistry_, 1920, p. 56).
W. A. Puckner, Secretary.
BUDWELL’S EMULSION OF COD-LIVER OIL, NOS. 1 AND 2
Report of the Council on Pharmacy and Chemistry
The Budwell Pharmacal Company, Lynchburg, Virginia, which markets these
preparations, claims that “No. 1” contains cod liver oil, “Iodide of
Arsenic,” “Iodide of Calcium,” and “Iodide of Manganese.” “No. 2” is
said to contain in addition to the ingredients of No. 1, creosote
carbonate and guaiacol.
It is known that arsenous iodid is decomposed by contact with water. It
is recognized that creosote carbonate is unstable and prone to liberate
creosote. Iodide of manganese not being official, the supply on the
market is not controlled in any way: Tests of purity are not prescribed
by the Pharmacopeia, the National Formulary, New and Nonofficial
Remedies or other books of standards. Therefore doubt must be expressed
as to the accuracy of the formulas as given. The Council cannot accept
such statements of composition without further evidence.
“No. 1” is commended for use in
“Chronic Rheumatism, Glandular Swellings, later forms of Syphilis,
convalescence from Scarlet Fever, La Grippe and Malaria, Chronic
Malarial Infection, Marasmus, Joint or other suppuration of
standing, diseases of skin, chorea, anaemia, neurasthenia,
obstinate neuralgia, scrofulous affections in general, and diarrhea
or dysentery (subacute or chronic) in childhood.”
“No. 2” is said to be
“Prepared especially for the treatment of Chronic Throat, Nasal,
Bronchial and Pulmonary Diseases.”
In the advertising circular statements regarding the various
ingredients of Budwell’s Emulsion are quoted from obsolete text
books. These statements, for the most part, do not represent modern
opinions on the subject. For instance, the circular praises the action
of guaiacol as eliminated directly by the lungs, thus exerting a
beneficial local effect and causing bacilli to diminish in numbers or
to disappear. All of this is directly contradicted in authoritative
modern publications on pharmacology, which hold that the excretion of
guaiacol by the lungs is infinitesimal and its action on bacilli is
nil. The Council held the preparations in conflict with its rules as
follows:
1. Many of the therapeutic claims are exaggerations.
2. The method of exploitation amounts to an indirect invitation to the
public to use these preparations as “consumption cures.”
3. The preparations are unscientific, they constitute a reprehensible
invitation to uncritical prescribing and their use is inimical to the
best interests of the profession and the public. It is difficult to
imagine in what conditions such a combination would be indicated. These
preparations are a remnant of the days of polypharmacy. Their use is
not in keeping with present medical thought and practice.--(_From The
Journal A. M. A., Feb. 20, 1915._)
RHEUMALGINE
Report of the Council on Pharmacy and Chemistry
Rheumalgine (Eli Lilly & Co., Indianapolis) is put up both in tablet
form and as a liquid. Each tablet, or teaspoonful of the liquid, is
said to contain:
“Strontium salicylate from Natural Oil 5 gr.
Hexamethylenamin 2 gr.
Colchicine 1/200 gr.”
The advertising matter contains several statements regarding the
individual ingredients to which objection must be made.
It is claimed (quoting from Hare) that strontium salicylate
“... is not so disagreeable to the taste as the corresponding
sodium salts, and more important still, it is far less apt to
disorder the stomach.”
“Taste” is a difficult subject to dispute; but in the experience of the
referee, patients object more to the strontium than to the sodium salt.
No evidence is submitted to prove that the strontium salt is less apt
to disorder the stomach. In observations made under the direction of
the referee, the nauseant and emetic doses are about the same as, or
even less than, those of sodium salicylate.
Under hexamethylenamin, the recommendations are not confined to
its recognized use as a urinary antiseptic; it is also said to be
“unexcelled” as a “germicide,” and to prevent the formation of urate
and phosphate deposits. These statements are contrary to facts.
“Rheumalgine ... may be used in all cases where the salicylates
are indicated. It is superior to preparations containing sodium
salicylate, in that it does not cause nausea or disturb the
digestion.”
Both the preceding statements are misleading. The necessity of giving
1/200 grain of colchicin for each 5 grains of salicylate would
certainly interfere with the use of adequate doses of the latter. The
colchicin would produce digestive disturbance quite apart from the
salicylate.
The mixture is described as:
“... ANTIRHEUMATIC, ANTIPYRETIC, URINARY ANTISEPTIC, AND URIC
ACID ELIMINANT. Useful in Acute Articular and Chronic Rheumatism,
Muscular Pains, Lumbago, Sciatica, Migraine of the Rheumatic, Gout,
and in Nervous Irritability of the Gouty or Lithemic.”
The facts are: Salicylates are useful in some of these conditions,
colchicin occasionally in a few, hexamethylenamin in none.
The combination is conducive to uncritical prescribing. For
instance, salicylates are effective in acute articular rheumatism;
hexamethylenamin and colchicin are useless; salicylates are of very
little use in chronic rheumatism, sciatica and nervous irritability,
while hexamethylenamin and colchicin are useless in these conditions;
colchicin is sometimes effective in gout, salicylates perhaps also;
hexamethylenamin is not.
Attention should also be called to the high dosage of colchicin,
namely, 1/100 to 1/50 of a grain of the alkaloid, every three or
four hours, the dose then to be “slightly reduced,” but continued
for several days; or in chronic cases, 1/100 to 1/30 grain per day,
continued indefinitely. This dosage appears high, if a really active
preparation is used.
Finally, the name “Rheumalgine” encourages thoughtless and unscientific
prescribing. If a mixture is used at all, the prescriber should be
constantly reminded of its composition.
It is therefore recommended that Rheumalgine be held in conflict with
Rules 6 (unwarranted therapeutic claims), 8 (nondescriptive name) and
10 (unscientific composition).--(_From The Journal A. M. A., June 26,
1915._)
GRAY’S GLYCERINE TONIC
Report of the Council on Pharmacy and Chemistry
The Council adopted the following report and authorized its publication.
W. A. Puckner, Secretary.
Gray’s Glycerine Tonic Comp. (Purdue Frederick Company, New York) is
a mixture said to be made according to a prescription of the late Dr.
John P. Gray, superintendent of the state hospital, Utica, New York. As
to the composition, the following statement is furnished by the company:
“This preparation is a combination of Glycerine, Sherry Wine,
Gentian, Taraxacum and Phosphoric Acid with carminatives.”
The label declares the presence of 11 per cent. alcohol, and the dose
is given at from two teaspoonfuls to a tablespoonful. A study of
the ingredients will show that, aside from the alcohol, the mixture
contains but one really active drug, gentian. Essentially, then,
“Gray’s Glycerine Tonic” is a mixture which, in addition to the
narcotic effect of the alcohol, depends on a bitter, gentian, for
whatever therapeutic action it may possess.
The bitters, of which gentian is a type, were once credited with
many therapeutic virtues which time has shown they do not possess.
Pharmacologic research has demonstrated that their utility consists in
stimulating the appetite through their action on the taste buds. On
this account they were believed also to increase the secretion of the
gastric juice by a psychic impression. More recently, however, even
this has been questioned--by Carlson, for instance.
These facts are fully understood, presumably, by all physicians. Yet,
according to the advertising circular, this “tonic,” which, for all
practical purposes, is merely a simple bitter, is good for thirty-two
diseases ranging from amenorrhea to whooping cough!
The conditions in which Gray’s Glycerine Tonic is asserted to be
especially efficient are described on the label of the bottle and the
outside wrapper, in popular terms, more or less typical of “patent
medicine” exploitation, such as “catarrhal conditions,” and “stomach
derangements.” Similar statements are contained in the leaflet
accompanying the trade package. For instance:
“It is, therefore, an effective, reliable tonic in nervous
exhaustion, general debility, impoverished conditions of the blood
and nervous system, Bright’s disease, diseases of the liver,
disorders of the urinary organs, etc.”
“It is an unexcelled restorative in that very common class of cases
in which there is no positive organic disease, but the patient
complains that he ‘does not feel well’ or ‘is out of sorts.’”
Here are some of the claims made in other advertising matter:
“All stages of bronchitis ... are rapidly improved by the use
of Gray’s Glycerine Tonic Comp. This remedy has a direct tonic
influence upon the circulation of the respiratory mucous membrane;
it relieves congestion and restores tone to weakened blood vessels.”
“... improves the appetite, gives valuable aid to the digestive and
absorptive processes, and reinforces cellular nutrition in ways
that insure a notable gain in vitality and strength.”
+-----------------------------------------------------------------+
| In Gastro-Intestinal Catarrh |
| |
| --and other afflictions of the stomach and bowels characterized |
| by muscular weakness and glandular insufficiency--there is no |
| remedy more prompt and effective in its action than |
| |
| Gray's Glycerine Tonic Comp. |
| |
| Under its systematic administration the appetite is restored, |
| the alimentary processes greatly improved, the nutrition |
| promoted and every vital function throughout the body given a |
| new and substantial impetus. As the digestive and assimilative |
| functions are restored to their normal efficiency, a notable |
| increase in the restorative and recuperative powers of the body |
| naturally follow. |
| |
| THE PURDUE FREDERICK CO. |
| 135 Christopher Street, New York City |
+-----------------------------------------------------------------+
Mention ILLINOIS MEDICAL JOURNAL when writing to advertisers.
[Illustration: This appeared in a journal owned and controlled by the
second largest state medical association of the country.]
Even granting that gentian may improve the appetite, how absurd it
is to claim that this mixture “relieves congestion,” “restores tone
to weakened blood vessels,” “gives aid to the absorptive processes,”
“reinforces cellular nutrition,” or increases vitality!
Neither the composition of Gray’s Glycerine Tonic nor the clinical
evidence warrants the belief that it has any therapeutic value other
than that due to the psychic effect of the bitter drug gentian.
Physicians who have prescribed it have done so because of the
advertising. This nostrum has been kept so constantly before the eyes
of medical men that they think of Gray’s Glycerine Tonic when they
cannot remember the official drugs that may be indicated in the case.
The moral is that liberal advertising will sell anything.
It is recommended that Gray’s Glycerine Tonic Comp. be declared not
eligible for inclusion in New and Nonofficial Remedies on account of
conflict with Rules 1, 6, 8 and 10.
[Editorial Note.--An old practice in hospitals--happily now practically
obsolete--was to have certain stock mixtures prepared in bulk. Among
these there was usually a so-called tonic mixture, used in a more or
less haphazard manner when nothing in particular seemed indicated. Such
a stock mixture was used in the State Hospital for the Insane at Utica,
N. Y., during the many years that Dr. John P. Gray was superintendent
(from the early fifties to the early eighties), although it is very
doubtful whether he originated the mixture. After the death of Dr.
Gray--so the story runs--one of his sons, with a partner, formed the
firm of Purdue Frederick Company, and began the exploitation of the
elder Dr. Gray’s name, in connection, presumably, with this stock
preparation. As indicated in the Council’s report, Gray’s Glycerine
Tonic Comp.--and what an absurd name!--is simply a mixture of ordinary
drugs, requiring no skill whatever in compounding. If there is a
physician living who cannot write a prescription offhand as good as
this formula, that physician should either go back to a medical school
or change his vocation. There is, and can be, no excuse for prescribing
such a ready-made mixture, for every cross-roads drugstore has the
ingredients and any pharmacist worthy of the name could compound it.
Among the scores of nostrums that disgrace the medical profession
of this country, none is more typical of all that is inimical to
scientific medicine, to the medical profession and above all to the
public--for, after all is said, it is the public that ultimately is
humbugged.]--(_From The Journal A. M. A., July 10, 1915._)
TONGALINE AND PONCA COMPOUND
Report of the Council on Pharmacy and Chemistry
The Council, having considered “Tongaline,” “Tongaline Tablets,”
“Tongaline and Lithia Tablets,” “Tongaline and Quinine Tablets” and
“Ponca Compound Tablets,” found these preparations ineligible for New
and Nonofficial Remedies and authorized publication of the following
report.
W. A. Puckner, Secretary.
TONGALINE
Tongaline (Mellier Drug Co., St. Louis) is a fancy name given to what
is essentially a sodium salicylate mixture. The air of mystery created
by the name permits the manufacturers to make claims for the product
which would be ludicrous if the medical profession was fully conversant
with the very ordinary character of the preparation.
Tongaline receives its name from tonga, an inert, long-discarded
mixture of various barks and herbs said to be gathered and prepared
by Fiji Islanders. Its constituents evidently tend to vary with
the collector. The history of the introduction of this indefinite
combination of simples is thus given in The Journal, May 10, 1913.
“A supply of the crude drug was carried to England by a man who had
lived for a short time in the Fiji Islands and it was placed in the
hands of a retail house in London. This occurred about 1879. In
1880, two English physicians of repute published laudatory articles
on the therapeutic value of tonga in neuralgia and rheumatism. This
created a demand for the drug which extended to the United States.”
Time showed that tonga was inert therapeutically, and authorities
on pharmacology now no longer notice it. As the Council previously
reported,[12] the indefinite character of the mixture should, alone,
be sufficient to exclude it from practical therapeutics. During the
temporary popularity of tonga, the proprietary mixture Tongaline was
put on the market for physicians’ use by the Mellier Drug Company,
St. Louis. In this, tonga was named as the active ingredient. The
commercial interests thus involved have faithfully nourished and kept
alive the “tonga” myth.
[12] Reports of the Council on Pharm. and Chem., 1912, p. 40.
In a recent advertising booklet, “The Therapeutic Properties of
the Ingredients of Tongaline,” the virtues of tonga, blue cohosh,
colchicum, jaborandi and salicylic acid are discussed. The label of a
recently purchased bottle reads:
“Tongaline contains Tonga, Cimicifuga Racemosa, Salicylate of
Sodium (the salicylic acid being made from pure natural oil)
Colchicum and Pilocarpin.”
It will be noticed that Tongaline is “made from the pure, natural oil.”
In fact, the statement is repeated in red ink, in large letters running
across the face of the label, thus emphasizing the alleged importance
of this assertion. In this connection it is only necessary to recall
that it has been proved clinically, chemically and physiologically that
there is absolutely no difference between the salicylic acid made from
the natural oil and the synthetic.
The formula was thus commented on in the article previously quoted from
The Journal:
“Tongaline ... is essentially a preparation of sodium salicylate,...
The Mellier Drug Company realized the impossibility of creating
any marked demand for a nostrum unless it had some real drugs
in it--hence the presence of the salicylates. What the actual
composition of Tongaline is, no one but the manufacturers know. At
one time the following was given as the formula:
Fluid Tonga 30 grains
Extract of Cimicifuga Racemosa 20 grains
Sodium Salicylate 10 grains
Pilocarpin Salicylate 1/100 grain
Colchin Salicylate 1/500 grain
“These amounts refer to the quantity of drugs in each fluidram of the
preparation. Whether the nostrum still has this composition we do
not know, but assuming that it has, it is quite evident that sodium
salicylate is the essential and active ingredient.”
The therapeutic indications given on the label of the bottle are:
“Rheumatism, Neuralgia, Grippe, Gout, Nervous Headache, Sciatica,
Lumbago, Malaria, Tonsillitis, Heavy Colds, Excess of Uric Acid,
and wherever the use of the Salicylates is indicated.”
In a recent booklet this semisecret salicylate mixture is recommended,
not only in conditions in which salicylates are indicated, but also
combined with aconite for rheumatic fever, with benzoate of soda in
the treatment of “grippe,” with potassium bromid in nervous headaches,
with gelsemium, glycerin and whisky for “heavy colds,” with ammonium
chlorid, stramonium and cimicifuga in “rheumatic dysmenorrhea,” and
even with mercury biniodid as a treatment of syphilitic eruptions!
“When administered with good judgment, Tongaline exerts a
stimulating effect upon every organ of elimination; cleansing
the complex sewerage system and putting it into working order.
When this is done, the sluggish blood current begins to flow more
freely; the lymphatic and glandular systems to give up and carry
off the toxic products, so long retained ...”
TONGALINE TABLETS
Then because of a “desire to put Tongaline in a more compact and
convenient form,” the same concern puts on the market Tongaline
Tablets. Whether Tongaline Tablets are of the same composition, the
doctor who prescribes them is not advised. In this form we have
Tongaline and Lithia Tablets, and Tongaline and Quinin Tablets.
Presumably those who are attracted by the word “lithia” are
sufficiently uncritical to be content with the statement that:
“The addition of Lithia to Tongaline presents a most useful
combination which does not rely upon its action on the kidneys
alone as is the case with Lithia salts or Lithia waters as
administered ...”
And the foregoing quotation, be it remembered, is for the information
of the medical profession! Tongaline and Lithia Tablets, we are
informed, are:
“... particularly indicated for certain diseases which are caused
by deposits of urates in the joints and kidneys, and can be used
with much benefit for many people who indulge in generous or
intemperate habits of living.”
Tongaline and Quinine Tablets are also exploited without statement
of composition. The promoters are probably justified in feeling that
physicians who prescribe quinin in combination with “Tongaline” care
little about the dosage.
It is unnecessary to discuss the silly claims made for Tongaline and
its combinations, although it is worth while to point out that the
prescribing of such nostrums by physicians is an imposition, if not a
fraud, on the public.
PONCA COMPOUND
Ponca Compound, also made by the Mellier Drug Company, St. Louis, is a
“female weakness remedy” in tablet form. The name suggests that “ponca”
is a medicinal substance, and, in fact, at one time, “Ext. Ponca” was
named as an ingredient. The nature of “Ext. Ponca” was apparently never
explained. It is now replaced in the “formula” by “senecin,” and the
only information concerning the composition at present given is:
“Ponca Compound Tablets Contain Extract of Mitchella Repens,
Senecin, Helonin, Caulophyllin and Viburnin.”
This “formula” is practically meaningless, not only because the
amount of each ingredient is not stated, but also because “senecin,”
“helonin,” “caulophyllin” and “viburnin” are in themselves variable
mixtures of unknown composition.[13]
[13] See Report of the Council on Pharmacy and Chemistry on “Resinoids
and Concentrations,” J. A. M. A., Nov. 13, 1909, p. 1655.
Presumably, “senecin,” “helonin,” “caulophyllin” and “viburnin” are
extractives of some kind prepared, respectively, from senecio aureus
(life root), helonias dioica (false unicorn), calophyllum thalictroides
(blue cohosh) and viburnum prunifolium or opulus (black haw or cramp
bark). These are, one and all, practically inert drugs. There is no
reason to believe that any or all of them can have any beneficial
influence in the many and varied conditions for which Ponca Compound is
advertised.
The following are excerpts from the advertising matter:
“Ponca Compound is a remedy of a very beneficial character for
Functional, Uterine and Ovarian troubles, which will respond to
internal treatment, especially when digital examination or surgical
interference is undesirable.”
“Ponca Compound is also valuable during gestation and after
parturition.”
“Uterine Alterative for Leucorrhoea, Dysmenorrhoea, Amenorrhoea,
Metritis, Endometritis, Menorrhagia, Metrorrhagia, Irregular
Menstruation, Subinvolution, Painful Pregnancy.”
It is recommended that Tongaline and Ponca Compound and all their
preparations be held in conflict with Rule 1, in view of their
semisecret and indefinite composition; with Rule 6, for the grossly
exaggerated therapeutic claims made for them; with Rule 8, because of
their misleading names, and with Rule 10, in view of their unscientific
character as irrational combinations. It is also recommended that this
report be published.--(_From The Journal A. M. A., July 17, 1915._)
ALFATONE
Report of the Council on Pharmacy and Chemistry
The Council has found Alfatone ineligible for New and Nonofficial
Remedies and has authorized publication of the following report.
W. A. Puckner, Secretary.
Alfalfa is good cattle feed but only nostrum exploiters have suggested
its use as a medicine for human beings. While it may seem a waste of
time to discuss the medicinal value of alfalfa its recent exploitation
by the Norwich Pharmacal Company, Norwich, N. Y., as “a reconstructive
tonic and nutrient” in the form of a mixture called “Alfatone,” calls
for comment. According to the label on the preparation:
“Each fluidounce represents:
Alcohol 15 per cent.
Medicago sativa (Alfalfa) 120 grains
Taraxacum 2-1/2 grains
Gentian 1 grain
Berberine Hydrochloride 1/40 grain
Glycerin and Aromatics.”
“Dose.--One to three fluidrams (4 to 12 c.c.) 4 times daily.”
Each maximum dose, therefore, should represent 45 grains of alfalfa, 1
grain of taraxacum (dandelion), 3/8 grain of gentian, 1/100 grain of
berberin hydrochlorid, and 27 minims of alcohol. Since the bitter drugs
are present in such small amounts that the preparation is almost devoid
of bitterness, and as the medicinal value of alfalfa is practically
nil, it is evident that whatever action Alfatone may have is due to the
stimulant effects of the alcohol.
Some of the claims made for Alfatone are:
“A reconstructive nutritive tonic indicated in general debility,
neurasthenia, convalescence, etc.”
“... a Galactagogue of merit as well.”
“... improves the appetite, aids the processes of digestion and
assimilation, facilitates elimination and effects gradual but
decided gains in strength, vitality and weight.”
It is suggested that:
“... in case of idiosyncrasy the addition of Tr. Nux Vomica 5 to 10
minims to the dose, unless contraindicated, will secure excellent
results.”
The Norwich Pharmacal Company naively remarks:
“The dearth of medical literature on Alfalfa has lead us to present
below a few of the findings of the Bureau of Plant Industry of the
Department of Agriculture ... as well as those from several state
experiment stations ...”
Here are the “findings”:
“... Digestible nutrients in 100 pounds of Alfalfa,... Protein,
11.0 pounds; Carbohydrates, 39.6 pounds; Ether Extract, 1.2 pounds.”
“... The high value of Alfalfa is due to the amount of protein that
it contains; to the large percentage of protein that is digestible
and the palatability of Alfalfa.”
“... Table showing pounds of elements removed from the soil by one
ton of crop.
Alfalfa Wheat
Potash 49.79 12.52
Phosphoric Acid 8.27 9.08
Lime 43.51 2.95
Nitrogen 44.01 22.30”
“... The abundance of muscle and bone producing material in Alfalfa
makes this crop especially good.”
Thus estimates of the value of a farm crop and cattle fodder are made
to do service as testimonials to its therapeutic merit for human
beings! Has the “patent medicine” promoter ever dared to insult the
intelligence of his patrons by a cruder absurdity? Yet it is not to the
nontechnical and unscientific public, but to a profession presumably
scientifically trained in pharmacology and therapeutics that this
concern presumes to offer its fodder tincture on the basis of testimony
to the agricultural value of the fodder plant.
Alfatone is a worthless alcoholic cordial. The audacity of the attempt
to promote its sale by a discourse on the merits of a well-known fodder
plant is the sole reason for devoting any attention to it. It is
recommended that Alfatone be held ineligible for New and Nonofficial
Remedies, and that this report be published.
[Editorial Note.--What a comment on American medicine that a concern
can even contemplate the possibility of making a commercial success
of the sale of such a silly nostrum as Alfatone! And yet, when one
remembers that a proprietary in which oats constitutes one ingredient
(“Pas-Avena”) for years has been advertised to physicians and
presumably prescribed by them, it is not altogether inexplicable that
business men should get the impression that the medical profession
is “easy” enough to “fall for” anything in the line of proprietary
mixtures. Perhaps we may look forward to being offered proprietaries
based on other cheap and well-known fodder plants. Tincture of Timothy
Hay, Blue Grass Tonic, Cornhusk Wine! Why not? The enterprising
companies that may put them out can easily publish tables to show
the digestible nutrients in each and indubitable testimony can be
furnished to prove the excellence of any of them as stock feed. If a
pitchforkful of timothy hay makes a good fattening ration for a growing
steer why should not a teaspoonful of tincture of timothy hay make a
“reconstructive tonic and nutrient” dose for a man? If an arm load of
thistles (carduus) makes a luscious food for _equus asinus_ why should
not a pinch of thistle in alcohol and water be a good “tonic”? Great
are the possibilities! They are limited only by the gullibility of the
medical profession and the public. Certain it is that some proprietary
manufacturers are firmly convinced that no combination can be too
preposterous to be worth trying on the medical profession.]--(_From The
Journal A. M. A., Aug. 7, 1915._)
ARTICLES REFUSED RECOGNITION
Report of the Council on Pharmacy and Chemistry
Below appear abstracts of the Council’s actions on articles refused
recognition which were not deemed of sufficient importance to require
lengthy reports.
Uricsol
Uricsol is marketed by the Uricsol Chemical Company, formerly of Los
Angeles, now of Boston. Regarding its composition only vague statements
are made. In an advertising pamphlet it is promised that the formula
will be sent to physicians on request. Such a request from a physician
elicited the following statement:
“URICSOL is a non-irritating, alkaline solution, containing Lithium
Citrate, Acid Citric and Potassium Nitrate, together with a saline
laxative in the form of Glycero Sodium Phosphate, with Vegetable
Tonics added.”
The Association Laboratory has made an examination of Uricsol to
determine its composition and reports as follows:
LABORATORY REPORT
A trade package purchased in March, 1915, from a wholesale drug house
was labeled:
“Uricsol Rheumatic Remedy, Uric Acid Solvent, Kidney and Liver
Stimulant, Manufactured by the Uricsol Chemical Co., Los Angeles,
Cal.”
This package was wrapped in a circular entitled “The Great California
Remedy--Uricsol.” The preparation is a viscid, slightly turbid light
brown liquid, with a faintly aromatic odor and a salty, bitter
taste. The diluted solution is acid in reaction toward litmus and
phenolphthalein and alkaline toward methyl orange.
Qualitative tests showed a presence of phosphate, citrate, nitrate,
sodium, glycerin, and a small amount of lithium in aqueous solution.
Besides these a small amount of some organic, nonalkaloidal substance
was found, which from its bitter taste suggested gentian. From the
qualitative tests it appeared that the phosphate was the predominating
ingredient and accordingly a phosphate determination was made. The
results, calculated to sodium phosphate, U. S. P., indicated the
presence of 64.20 gm. per 100 c.c., held in solution by citric acid and
sodium nitrate.
Uricsol evidently is a solution containing a large amount of sodium
phosphate with small amounts of lithium, nitrate, citric acid and
glycerin, with probably some vegetable extract.
In general Uricsol is similar to the once widely exploited proprietary
“Melachol,” which has been frequently imitated. A preparation
essentially identical is in the United States Pharmacopeia, under the
title “Compound Solution of Sodium Phosphate.”
The Uricsol Company calls its preparation
“... the latest word in the treatment of Rheumatism and that allied
group of ailments which is caused by an excess of Uric Acid.”
Hay fever, bronchial asthma and neuritis are conditions in which it is
recommended. The claim is made that
“Uricsol quickly controls Vasomotor Rhinitis and eliminates such
conditions from the system.” “In fact, it will correct FAULTY
METABOLISM.”
To a few practitioners of an older generation the pharmacologic basis
of a remedy for rheumatism was sufficiently defined by saying that it
increased the solubility of uric acid or affected it in some way. This
theory is obsolete; there is not, and never was, any reliable evidence
on which to base the theory that rheumatism is in any way caused by
uric acid. The exploitation of Uricsol as a “uric acid solvent” is
merely another illustration of the way in which nostrum manufacturers
play on disproved theories. Of course the claim that sodium phosphate
has any particular power to control vasomotor rhinitis, hay fever,
asthma, and to correct faulty metabolism is foolish.
To summarize: Uricsol is a mixture of well-known drugs, marketed with
false claims as to therapeutic action, with misleading and meaningless
statements as to composition and under a name which invites uncritical
prescribing. Uricsol is held ineligible to inclusion in New and
Nonofficial Remedies.
Jubol
The following ridiculous statements are addressed, not to the laity,
but to the medical profession:
DO YOU SUFFER FROM Constipation--Hemorrhoids--Enteritis--Mucous
discharge--Pituita--Acidity of the stomach--Vertigo--Sick
Headache--Disturbed Sleep--Insomnia--Sallow Complexion--Coated
Tongue--Offensive breath--Fatigue and depression--Boils--Pimples?
“ONE of these symptoms alone shows that there is defective or
insufficient function of the intestines, even if the stools are
regular.
“Excrements remain too long in the intestine and set up
fermentation. The harmful poisons and Ptomains which they produce
are re-absorbed by the blood and poison the whole system.
“The Intestines must be cleared and re-educated with JUBOL.
“Jubolise your Intestines.”
Jubol tablets are sold in the United States by Geo. J. Wallau, Inc.,
New York, and are said to be prepared by J. L. Chatelain, Paris,
France. The following incomplete and nonquantitative “formula” is
furnished:
“... compounded chiefly [!] of Agar-Agar, Biliary Extracts and pure
Extracts from all the intestinal Glands.”
It is asserted that
“The tablets are coated with a protective covering in order that
they may act on the intestine only.”
The tablets contained in a regular-size trade package, obtained direct
from the agent, readily separated into two halves and disintegrated
within a few minutes when agitated with water. It is thus evident
that, under ordinary conditions, the intestinal ferments in Jubol (if
they are present, as claimed) would be destroyed during their passage
through the stomach. In direct tests, however, practically no tryptic
activity was demonstrated.
The composition of Jubol is not declared; grossly unwarranted and
incorrect claims are made for its therapeutic actions; the name does
not indicate the alleged ingredients and so much of the composition as
is declared indicates an unscientific mixture. The Council decided that
Jubol should be held ineligible for New and Nonofficial Remedies, and
that this report should be published.
Urodonal
Urodonal is said to be “produced in the laboratory of J. L. Chatelain,”
Paris, France. It is marketed in this country by Geo. J. Wallau, Inc.,
New York.
The preparation is claimed to be a chemical compound, and the
advertising matter furnishes a “formula,” which consists of the
formulas of lysidin, sidonal and hexamethylenamin, connected by plus
signs:
{H₂C Az } CO₂H--C--OH AzH Az
{H₂C C--CH₃} + { H₂C CHOH } {H₂C CH₂} {H₂C CH₂ CH₂}
{ AzH } {OHHC CH₂ } {H₂C CH₂} + {Az.CH₂ Az.CH₂ Az}
{ CHO } { AzH } { CH₃ }
That the substance is a chemical compound is highly improbable, and no
evidence has been submitted to substantiate the claim. On the contrary,
in the following statement the phrase “based on” is a virtual admission
that the preparation is merely a mixture:
“Urodonal ... is a granular effervescent preparation based on
methylglyoxalidine [Lysidine], quinate of diethylene-diamine
[Sidonal] and hexamethylene-tetramine [Formin, urotropine].”
Mystery is added by the mention of undefined “special products” in the
following:
“The fact of combining these two salts [lysidin and sidonal] in
Urodonal, in strictly determined proportions and in the presence of
special products, gives this preparation very considerable power in
dissolving uric acid.”
These contradictory statements of composition conflict with Rule 1.
Urodonal is marketed in typical “patent medicine” style: the name
“Urodonal” is blown in the bottle and the label contains a list of
“Indications,” including rheumatism, gout and gravel (Rule 4). That
this form of marketing has introduced it to the public is suggested by
the following in an advertising circular:
“... Urodonal is now popular--even classic--throughout the world,
where thousands of doctors and millions of patients agree in
asserting that ‘Urodonal is to rheumatism what quinine is to
fever.’”
There are also other indications that the mixture is to be exploited to
the laity. For instance, the U. S. distributor sends out a portrait of
Sarah Bernhardt bearing the legend:
“I am positive that URODONAL preserves youth’s freshness with
clearness and strength to brain and heart. I have taken it for two
years with the greatest benefit. Sarah Bernhardt.”
A circular advises this mixture
“For all who suffer from Arthritis, Rheumatism, Arterio-Sclerosis,
Renal and Bilious Lithiasis, Headache, Gout, Gravel, Lumbago,
Sciatic Pains, Neuralgia and all uric acid troubles.”
“In fact, Urodonal is five times more active than piperazine, and
thirty-seven times more active than lithia. We are, therefore,
entitled to say that no other eliminator of uric acid can be
compared with it.”
“Being _37 times more active than lithia_, it clears the heart
valves of any sandy substances which may clog them, and checks the
atheromatous degeneration of the blood vessels.”
These extracts indicate sufficiently the extravagant tone of the
advertising (Rule 6): None of the ingredients are notably active in
dissolving uric acid when administered by mouth. None produce any
marked increase of uric acid elimination. No intelligent physician
would use a uric acid solvent for “bilious lithiasis”; and their
usefulness in the other conditions is open to doubt, to put it mildly.
Although the preparation is a simple mixture, the name does not
indicate the components, but inclines to therapeutic suggestion (Rule
8).
Nothing is to be gained by combining several drugs which are useless,
severally, for the purpose intended, as in the present case (Rule 10).
Urodonal is marketed under inconsistent statements of composition and
with exaggerated therapeutic claims; the name is nondescriptive and
the mixture is unscientific. The Council decided that the preparation
should be declared ineligible for conflict with Rules 1, 4, 6, 8 and 10
and that this report should be published.--(_From The Journal A. M. A.,
Aug. 14, 1915._)
FORMAMINT
Report of the Council on Pharmacy and Chemistry
The following report has been authorized for publication.
W. A. Puckner, Secretary.
Formamint is a proprietary medicine manufactured by the A. Wulfing
Company (New York, London and Berlin), which is affiliated with the
Bauer Chemical Company.
It has been widely advertised in Europe for several years, and is now
on the American market;[14] it is advertised in this country both in
newspapers and medical journals.
[14] The Journal A. M. A., Feb. 24, 1912, p. 572.
Following is a brief review of the more important alleged
investigations that have been reported from time to time in various
European journals.
In “The Therapeutical Value of Foramint in Septic Affections of the
Oro-Pharynx,” De Santi[15] quotes Rosenberg,[16] who reports the
successful use of Formamint in cases of streptococcus infections,
tonsillitis and acute symptoms of chronic sore throat. According
to Seifert,[17] Formamint is a chemical combination of formaldehyd
and milk sugar. When the tablets are dissolved in the saliva, 0.01
per cent. of formaldehyd in its “status nascendi” is liberated and
exercises a strong disinfectant action. Seifert states that the
preparation is markedly palatable, since it contains a little citric
acid to render the taste cool and refreshing. In some experiments with
streptococci, pneumococci, typhoid and diphtheria bacilli, Seifert
found that a solution of one tablet in 10 c.c. of water destroyed
these germs in from five to ten minutes. A solution of the same
strength was also added to culture tubes of broth, agar, and gelatin,
with the result that no growth occurred in them, while distinct and
characteristic development of the bacteria took place in control
tubes. He does not state, however, how much Formamint solution was
added to the mediums.
[15] De Santi: Medical Magazine =16=:141, 1907.
[16] Rosenberg: Lancet, London =2=:1871, 1905.
[17] Seifert: Pharmakol. u. therap. Rundschau, 1904, No. 14; quoted by
De Santi (Note 2).
Daus[18] reports successful treatment of tonsillitis, mumps and middle
ear diseases. In these cases no other gargles or mouth washes were
used. He states that no indication of irritant or other injurious
action made its appearance even after large doses. In the same article,
F. Levy reports experiments as follows: Agar plates were prepared with
a culture of streptococcus from a severe case of quinsy. One half of
the plate was rubbed with saliva containing Formamint in solution.
(The strength of the solution used is not given.) In twenty-four hours
streaks of growth had appeared on one portion of the plates while the
part on which the Formamint saliva had been rubbed remained sterile.
Daus also found that agar and broth cultures of streptococcus shaken
with Formamint saliva remained sterile.
[18] Daus: Med. Klin. =2=:4110, 1906.
Rheinboldt,[19] investigating the effects of Formamint and of ordinary
formaldehyd on animals, concludes that formaldehyd is toxic in action
while Formamint is not.
[19] Rheinboldt: Deutsch. med. Wchnschr. =32=:587, 1906.
[Illustration: How the exploiters of Formamint capitalize the medical
profession. Miniature reproductions of typical Formamint advertisements
appearing in the newspapers.]
Rosenberg[20] corroborates this statement. He also found that agar
plates of _Bacillus prodigiosus_ were killed by Formamint solutions
in about four hours. He fails, however, to give the strength of his
Formamint solutions.
[20] Rosenberg: Therap. d. Gegen. =7=:55, 1905.
Wingrave[21] suggests the use of Formamint for infants! He recommends
that a tablet be crushed and wrapped in “butter cloth.” The ends of the
cloth are to be tied with thread, the Formamint is to be moistened, and
the packet is to be held in the mouth of the baby several times each
day.
[21] Wingrave: Lancet, London =2=:1067, 1906.
Young[22] published the results of some experiments by himself and
Delépine on the human throat. They dissolved a tablet in the mouth and
made swab cultures with the following results:
Immediately after taking the tablet 0 colonies
10 minutes after taking the tablet 35 colonies
30 minutes after taking the tablet 150 colonies
[22] Young: Lancet, London =1=:975, 1908.
They found no staphylococci at any time. Other results of swabbing
various parts of the throat before and after the use of Formamint,
reported by these investigators, show enormous reductions in the count,
claimed to be due to the action of Formamint. The count was made on
agar at 37 C., but they fail to state the time elapsing between taking
the Formamint and making the swab. Young also reports favorable
clinical results in cases of scarlet fever, diphtheria, sore throat,
and the like. It must be noted, however, that they state that the mouth
and fauces must first be thoroughly cleansed by swabbing and douching
before Formamint is used.
THE “CHEMICAL COMPOUND” CLAIM
The claims made in the advertising literature of Formamint are very
extravagant. Many are highly improbable. These statements will be
discussed later.
The statement is made that Formamint is a new chemical compound:
“Formamint is Pentamethanallactose, 5 CHOH + C₁₂H₂₂O₁₁. It is an
original combination of Formaldehyde with Lactose, a definite
chemical compound. The Formaldehyde molecule is locked up in it
until solution in the saliva takes place, when the Formaldehyde is
liberated in its _nascent_ state and is therefore active without
being irritant.”
Furthermore the makers contend that this new chemical compound is
entirely harmless. For example, Daus,[5] in an article on “The
Disinfectant Action of Formic Aldehyde on Mucous Membranes,” declares:
“No indication of irritant or other injurious action made its
appearance even after large doses. The urine remained free from
albumin and sugar.”
Such statements as these are found in the advertising literature:
“Formamint tablets are absolutely harmless and innocuous, even to
little children.”
“When dissolved in the saliva, Formamint Tablets liberate slowly
Nascent Formaldehyde in a most active yet non-irritant form.”
They maintain that Formamint is not only absolutely harmless, but
actually beneficial to the tissues. It may be used “to tone up and
strengthen the tissues, prevent hoarseness, and allay irritation in
singers, public speakers,” etc.
The claims urged as to its germicidal power are indeed glittering. This
“new chemical compound” is claimed to liberate formaldehyd in some new
and peculiar condition which, while it has a soothing and tonic effect
on the cells of the human tissues, can at the same time quickly kill
any form of bacterial life.
“Dissolving readily, it releases its germicidal, antiseptic
qualities, which impregnate the saliva and are carried naturally
and easily around the mouth and in the deepest crevices of the
throat--destroying the germs where they are causing the mischief.
Formamint prevents and destroys infectious germ life in a soothing
grateful way.”
“In the saliva it frees a germicide, fatal to germs but harmless
to the most delicate membranes. And flowing into every tiny corner
of the gums, tonsils and throat, into places where no gargle ever
reaches, it most effectively _disinfects_ the throat.”
The claims as to the preventive and curative effects of the preparation
cover a large portion of the category of human ailments and distresses.
The following quotations indicate some of its supposed properties:
“... it is therefore self-evident that Formamint should be
looked upon as a necessary part of the treatment of all forms of
tonsillitis.”
“The value of Formamint is equally great in diphtheric tonsillitis,
or as a prophylactic ...”
“The extraordinary success which I had with Formamint in a
school epidemic of scarlet fever during May and June, 1907, was
the determining factor which induced me to abandon the use of
inhalations, gargles, local applications in the treatment of
diseases of the throat, and to use Formamint exclusively for the
future.”
“There are naturally many similar conditions in which Formamint
may be used as a prophylactic, notably scarlet fever, mumps,
streptococcal and staphylococcal sore throats, ‘milk outbreaks’ of
sore throat, drain throats, hospital throats, and the like.”
“Formamint Tablets are indicated in Angina, Tonsillitis,
Pharyngitis, Stomatitis, Gingivitis, Glossitis, ulceration, spongy
or bleeding gums, Pyorrhea Alveolaris, ‘Smoker’s Sore Throat,’
Abscess or Boils, etc.”
“As a _Prophylactic_ against Diphtheria, Scarlet Fever,
Influenza, Measles, Epidemic poliomyelitis, and other pathogenic
micro-organisms. To neutralize putrefaction products in and about
the teeth, correct fermentative processes, deodorize and purify the
breath, etc.”
“To _tone up_, and _strengthen_ the tissues, prevent _hoarseness_
and _allay irritation_ in singers, public speakers, neutralize the
effects of dust-infection or _disinfect the saliva or sputum_ in
Influenza, Tuberculosis, etc.”
One man declares that along with specific constitutional treatment he
“had the best results from the use of Formamint tablets” in a case of
syphilitic ulceration of the tongue.
In short, Formamint is recommended for the treatment or prevention
of almost everything, from a bad breath to such grave conditions as
scarlet fever, diphtheria and tuberculosis, conditions in which a
delay in proper treatment--for instance, in diphtheria, a failure to
administer antitoxin--may result in the death of the patient.
A series of investigations was therefore undertaken in order to
discover whether the extravagant claims regarding the germicidal power
of Formamint could be verified.
Experimental Data
Two fifty-cent bottles of Wulfing’s Formamint were purchased in the
open market and were kept well stoppered to prevent deterioration.
Qualitative tests showed the presence of formaldehyd and the amount was
determined quantitatively by the hydrogen peroxid method as given by
Sutton.[23] The results were respectively, 1.99 per cent. and 2.03 per
cent. of formaldehyd.
[23] Sutton: Volumetric Analysis, Edition 10, p. 390.
[Illustration: Two Formamint advertisements reproduced in miniature
typical of those appearing in a certain type of medical journals.]
Some determinations were made of the germicidal power of Formamint
in vitro, that is, under controlled laboratory conditions. A
twenty-four-hour plain agar culture of _Staphylococcus aureus_ was
washed off in 10 c.c. of sterile 0.85 per cent. sodium chlorid
solution. A 1:100,000 dilution of this was made in each of three flasks
containing 100 c.c. of sterile saliva. Flask 1 contained 1 per cent. of
Formamint, Flask 2, 5 per cent.; Flask 3, containing no Formamint, was
kept as a control. At intervals samples were removed and dilutions made
and plated in duplicate on standard agar. The plates were incubated
twenty-four hours at 37 C., and plates containing less than 200
colonies were counted. The results are given in Table 1. After seven
days there was no appreciable difference in the plates.
Another test was made by adding a 1 per cent. Formamint solution to
plain agar plates inoculated with _B. coli_. A twenty-four-hour plain
agar culture of _B. coli_ was washed off in 10 c.c. of sterile 0.85 per
cent. sodium chlorid solution. A 1:1,000,000 dilution was made of this
and 1 c.c. added to each plate. Varying amounts of 1 per cent. solution
of Formamint were added to each plate. They were incubated seventy-two
hours at 37 C. After seven days’ incubation the count was the same. The
results are given in Table 2.
Another experiment was made thus: One loopful of a twenty-four-hour
plain agar culture of _Streptococcus lacticus_ was mixed with a tube
of North medium. One loopful from the inoculated tube was mixed with a
second tube of North medium. Both tubes were poured into Petri dishes
and allowed to cool. One half of each plate was well smeared with a 10
per cent. solution of Formamint in saliva. After twenty-four hours’
incubation at 37 C., only a few colonies appeared on the side to which
the Formamint had been applied, while the other half was thickly
covered with colonies.
TABLE 1.--SHOWING TIME IN WHICH CULTURES OF STAPHYLOCOCCUS AUREUS WERE
KILLED BY DIFFERENT AMOUNTS OF FORMAMINT
===================+=================+=============+=================
Amount of Formamint| Period of |Average Count| Count on Flask
in Saliva |Standing at 37 C.| When Plated |of Saliva Without
(Per Cent.) | (Hours) | | Formamint
-------------------+-----------------+-------------+-----------------
1 | 3 | 32 | 3200
1 | 6 | 0 | 7000
5 | 1 | Few | 5000
5 | 2 | 0 | 4100
5 | 3 | 0 | 3200*
5 | 6 | 0 | 7000*
-------------------+-----------------+-------------+-----------------
* The last two observations were made at the same time as on the 1 per
cent. solutions.
This work so far corroborates that reported in the literature quoted
by the manufacturers. But the fact that a compound is a germicide when
brought into intimate contact with bacteria in a solution or medium in
a test tube or flask does not prove that it will be effective when used
in the human throat.
THE ALLEGED GERMICIDAL ACTION
An attempt was made to discover whether or not the claims advanced by
the manufacturers as to the perfect germicidal action of Formamint in
all the nooks and crannies of the mouth and throat could be confirmed.
TABLE 2.--COUNT OF B. COLI CULTURES WITH DIFFERENT AMOUNTS OF FORMAMINT
======================================================================
No. c.c. of 1 per cent. Formamint 0 0.1 0.3 0.5 0.7 1.0 1.5 2.0 3.0
Count 160 33 39 26 15 12 2 0 0
----------------------------------------------------------------------
The first step in attacking this problem was to make comparative counts
of the number of bacteria in the throat before and after the use of
Formamint. The methods employed were as follows: The throat was gargled
with 50 c.c. of sterile 0.85 per cent. sodium chlorid solution. In
each case the same length of time, as far as possible, was used in the
process. The liquid was collected in a sterile flask. The gargling in a
series of experiments was begun not less than two hours after a meal.
After some preliminary work the following dilutions of the 50 c.c. of
salt solution were found sufficient: 1:1,000, 1:10,000 and 1:100,000.
Plates were made in duplicate from each dilution and incubated
seventy-two hours at 37 C. The counts were made on plates containing
less than 200 colonies. Except where otherwise noted standard agar was
used. The mediums were always prepared in the same way.
All the work was carried out under conditions as nearly natural
as possible. The Formamint was taken according to the directions
accompanying the trade package. Every opportunity was given the
Formamint to penetrate all the crypts and recesses about the mouth
and throat. The tablet was allowed to dissolve as slowly as possible,
the time usually being five to six minutes, and saliva was thoroughly
forced around the mouth before being swallowed. Plating was always
done immediately after gargling so that no growth could occur in the
salt solution. The results are given in Table 3. The numbers are
average counts from several plates and calculated to show the number of
bacteria washed out by the 50 c.c. of salt solution.
TABLE 3.--SHOWING THAT FORMAMINT DOES NOT GREATLY DECREASE THE NUMBER
OF BACTERIA IN THE THROAT
==========================+=========+=========+===========+===========
| | |No. Found |No. Found
| Time |Amount of|in Throat |in Throat
Conditions of Test | Since |Formamint| Before | After
|Preceding| Used | Use of | Use of
| Test | |Formamint |Formamint
--------------------------+---------+---------+-----------+-----------
Normal | ... | 0 | 15,600,000| ...
Normal | 1 hour | 0 | 38,500,000| ...
Normal | 1 hour | 0 | 30,500,000| ...
Normal | ... | 0 | 12,500,000| ...
Normal | 1 hour | 0 | 14,500,000| ...
| 1 hour | 0 | 23,500,000| ...
Tablet dissolved in mouth | 6 days | 1 tablet| ... | 15,000,000
and throat gargled one | | | |
hour later | | | |
Throat again gargled two | 1 hour | 0 | ... | 10,050,000
hours after Formamint | | | |
was used | | | |
Normal | 7 days | 0 | 62,000,000| ...
Normal | 1 hour | 0 | 72,500,000| ...
Normal | ... | ... | 61,000,000| ...
Tablets were taken, one | 2 days | 12 | ... | 39,100,000
per hour, and throat | | | |
gargled onehour after | | | |
last tablet was taken | | | |
Throat was again gargled 2| 1 hour | 0 | ... | 59,000,000
hours after taking last | | | |
tablet | | | |
Normal | 5 days | 0 | 35,000,000| ...
Normal | 1 hour | 0 | 62,000,000| ...
Normal | 1 hour | 0 | 72,000,000| ...
One tablet was taken each | 4 days | 24 | ... |175,000,000
half hour for 12 hours | | tablets | |
consecutively. Throat was| | | |
gargled one hour after | | | |
last tablet was taken | | | |
Throat was again gargled | 1 hour | 0 | ... |168,750,000
two hours after last | | | |
tablet was taken | | | |
Normal | 3 days | 0 |129,600,000| ...
Normal | 1 hour | 0 |177,000,000| ...
Normal | 1 hour | 0 |147,000,000| ...
Normal | 3 days | 0 | 79,000,000| ...
One tablet was taken | 1 hour | 1 | ... | 83,200,000
immediately after preced-| | | |
ing gargle. Throat was | | | |
again gargled at end of | | | |
one hour | | | |
Throat was again gargled 2| 1 hour | 0 | ... |134,750,000
hours after tablet was | | | |
taken | | | |
Normal conditions except | 19 days | 0 | 32,600,000| ...
that mouth and teeth were| | | |
throughly washed with | | | |
soap just before gargling| | | |
Same as above | 1 hour | 0 | 33,125,000| ...
Same as above | 1 hour | 0 | 40,375,000| ...
Teeth were not washed. | 2 days | 0 | 33,500,000| ...
Otherwise normal con- | | | |
ditions | | | |
Same as above | 1 hour | 0 | 43,330,000| ...
Same as above | 1 hour | 0 | 54,000,000| ...
Same as above | 1 hour | 0 | 50,000,000| ...
Same as above | 1 hour | 0 | 67,000,000| ...
Mouth and teeth thoroughly| 2 days | 0 | 5,270,000| ...
washed with soap just | | | |
before throat was gargled| | | |
Same as above | 1 hour | 0 | 10,916,000| ...
Same as above | 1 hour | 0 | 8,275,000| ...
Normal conditions, but 1 | 3 days | 0 |228,750,000| ...
c.c. of sterile rabbit’s | | | |
blood was added to each | | | |
plate | | | |
Count from the same gargle| 0 | 0 | 60,625,000| ...
as above. No blood used | | | |
in the plates | | | |
Normal conditions, but | 1 hour | 0 |431,250,000| ...
count was made on blood | | | |
agar | | | |
Count from the same gargle| 0 | 0 | 59,625,000| ...
asabove. No blood used in| | | |
the plates | | | |
Normal conditions, count | 2 days | 0 |683,300,000| ...
was made on blood agar | | | |
Same gargle as above, but | 0 | 0 | 58,500,000| ...
count was made on plain | | | |
agar | | | |
One tablet was taken just | 1 hour | 1 tablet| ... |558,300,000
after preceding gargle. | | | |
After one hour throat was| | | |
again gargled. Count on | | | |
blood agar | | | |
Same gargle as above, but | 0 | 1 tablet| ... | 55,875,000
count was made on plain | | | |
agar | | | |
Normal conditions | 2 days | 0 | 79,125,000| ...
One tablet was taken just | 1 hour | 1 tablet| ... | 56,250,000
ten minutes before gargle| 16 min. | | |
was made | | | |
Normal conditions | 2 days | 0 | 46,750,000| ...
One tablet was taken just | 1 hour | 1 tablet| ... | 38,500,000
ten minutes before throat| | | |
was gargled | | | |
Teeth and mouth were thor-| 5 days | 0 | 47,370,000| ...
oughly washed with soap | | | |
just before gargle was | | | |
made | | | |
Teeth washed as above and | 1 hour | 1 tablet| ... | 21,225,000
1 tablet taken 10 minutes| | | |
before gargle was made | | | |
--------------------------+---------+---------+-----------+-----------
Finally a determination was made of the number of streptococci in the
throat before and after the use of Formamint. The throat was gargled
in the manner previously described. The streptococcus count was made
by the dilution method as given by Heinemann.[24] Culture tubes were
used instead of fermentation tubes. One per cent. dextrose broth was
the medium employed. One cubic centimeter was added to each of a series
of ten tubes for each dilution and the following dilutions were used:
1:10,000, 1:100,000 and 1:1,000,000.
[24] Heinemann: Laboratory Guide in Bacteriology, p. 86.
The results given in Table 4 are the average count from a number of
dilutions and are reported as the total number washed out by the
50 c.c. of salt solution.
TABLE 4.--SHOWING THAT FORMAMINT FAILS TO REDUCE THE NUMBER OF
STREPTOCOCCI IN THE THROAT
==============+===========+===========+===========+==========
| | | No. Found | No. Found
| Time | Amount of | in Throat | in Throat
Conditions | Since | Formamint | Before | After
of Test | Preceding | Used | Use of | Use of
| Test | | Formamint | Formamint
--------------+-----------+-----------+-----------+----------
Normal | .... | 0 | 1,200,000 | ....
| | | |
One tablet was| | | |
taken and | | | |
throat gargled| | | |
one hour later| 4 days | 1 tablet | .... |14,750,000
| | | |
Normal | 3 days | 0 | 9,950,000 | ....
| | | |
One tablet was| | | |
taken and | | | |
throat gargled| | | |
ten minutes | | | |
later | 1 hour | 1 tablet | .... | 8,000,000
==============+===========+===========+===========+==========
Discussion
The contention that Formamint contains formaldehyd was confirmed by
analysis.
The manufacturers also maintain that Formamint is a new, definite
chemical compound, consisting of five molecules of formaldehyd and
one molecule of lactose, and that when dissolved in the saliva the
formaldehyd is liberated in some new and peculiar form, which they
call nascent formaldehyd. This new kind of formaldehyd is, according
to the advertising literature, especially powerful in its germicidal
properties and at the same time has absolutely no irritating or harmful
effects.
NOT A CHEMICAL COMPOUND
Thoms,[25] retained as an expert by the German government, decided,
after a series of chemical investigations, that Formamint was not
a definite chemical compound, but that it was probably a solid
solution of formaldehyd in lactose. He proved that when the process
of manufacture was carried out in exactly the way called for by the
Formamint patents, compounds containing a greater or less per cent. of
formaldehyd could be made while the other properties remained similar
to those of Formamint. The composition of the final product depended
on the proportion of the components used in the process. Therefore
Formamint did not form a safe means of uniform dosage.
[25] Thoms: Arb. a. d. Pharm. Inst. d. Universität, Berlin =11=:210,
1914.
As a result of Thoms’ work the German courts held that Formamint was
not a new chemical compound. Consequently the Formamint patent (Number
189036) was annulled in Berlin, Nov. 29, 1913.
Again the contention that formaldehyd in the nascent or active
condition is less poisonous and irritating than in its ordinary form is
contrary to what would be expected from the behavior of such compounds.
If it were liberated, as claimed, in the “nascent” condition, it would
be, for that very reason, not only more active but also more harmful.
As a matter of fact, Formamint did have an irritant effect on the
worker who carried out these investigations. When one tablet was
taken each hour for twelve consecutive hours, marked irritation of
the intestinal tract resulted. There was almost sufficient nausea to
cause vomiting and uneasiness in the alimentary canal following the
experiment. When the twenty-four tablets were taken the results were
similar but more pronounced. This is decidedly in contradiction to the
assertions of the manufacturers.
Otto Seifert,[26] moreover, cites the following:
“By Effects: Only a few patients complain of an unpleasant sharp
taste, burning of the tongue (Seifert, Sklarek). Among the general
symptoms observed are urticaria-like exanthems (Glaser, Roters),
which are accompanied by nausea, vomiting, headache, insomnia
and vertigo, burning and irritability especially in the larynx
(Meissner); phenomena of poisoning (Geissler); gastric disturbances
(Engelmann); renal irritation (Steinhard); unsuited for diabetics
(Voit).”
[26] Seifert, Otto: Die Nebenwirkungen der modernen Arzneimittel, 1915.
The contention that Formamint, when mixed directly with mediums
and left in contact with bacteria, will kill the organisms was
corroborated. Thus the statements and pictures in the booklet, “The
Gospel of Prevention,” which is enclosed with each bottle of Formamint,
showing the inhibition of growth of air bacteria on plates containing
Formamint are no doubt true and authentic.
Finally, the claim that Formamint is an almost perfect throat
disinfectant was by no means confirmed, as a glance at the tables will
show. One hour after it is taken, even when a tablet was used each
half hour for twelve hours, the number of bacteria in the throat was
practically the same as when Formamint was not used. Even ten minutes
after taking a tablet the number of bacteria in the throat was never
greatly reduced, as is maintained by the manufacturers.
HAS NO SELECTIVE ACTION
Formamint exerts no selective action in killing off the very delicate
organisms which are more apt to be pathogenic. When the comparative
counts were made on blood agar which would favor the growth of the
delicate parasitic organisms, no reduction whatever was shown by the
use of Formamint.
The number of streptococci was found to be the same, within limits of
experimental error, ten minutes after taking a tablet as it was before
the tablet was taken.
Therefore it seems that Formamint fails, as any such germicide would
be expected to fail, to kill bacteria in the crypts and recesses of
the throat, for when dissolved in the mouth it cannot reach and remain
in contact with the organisms long enough to kill them before it is
swallowed.
SUMMARY
Summed up, the investigation shows:
1. That the claims made for Formamint are extravagant and misleading.
2. That the recommendations for the use of these tablets may be, in
some cases, fraught with danger and are a menace, not only to the
health of the individual, but also to the safety of the community.
3. That the claim that Formamint is a definite chemical compound is
false.
4. That the use of Formamint may produce marked irritation of the
intestinal tract.
5. That Formamint is not a throat disinfectant, as the manufacturers
maintain, but its action on the bacteria of the throat is an almost
negligible one and dependence on Formamint for the prevention of
infection and for curing disease is not only unwise but dangerous.
6. That Formamint conflicts with the rules of the Council. False
statements are made with regard to its composition (Rule 1); grossly
unwarranted claims are made for its therapeutic properties (Rule 6),
and therefore its exploitation to the public (Rules 3 and 4) is a
public danger.
It is recommended that this report be published, to call attention not
only to the falsity of the claims made for, and the danger in the use
of, Formamint, but also to emphasize the utter inefficiency of all such
methods of “disinfecting” the throat.--(_From The Journal A. M. A.,
Aug. 28, 1915._)
HYDRAGOGIN
Report of the Council on Pharmacy and Chemistry
Hydragogin (C. Bischoff & Co., New York, selling agents) is advertised
as “a most powerful diuretic and cardiac tonic.” The composition given
is:
“Fifteen parts of the remedy contain 0.5 parts oxysaponin, 1.5
parts tincture of digitalis, 2.5 parts tincture of strophanthus,
scillipicrin and scillitoxin, the active principles of scilla
maritima, and alcohol.”
It is not clear from this statement whether 15 parts of Hydragogin
contain 2.5 parts of tincture of strophanthus, plus unspecified
amounts of scillipicrin and scillitoxin, or 2.5 parts of a mixture,
in unspecified proportions, of tincture of strophanthus, scillipicrin
and scillitoxin. The activity of strophanthus, after it enters the
blood stream, is about fifty times that of digitalis; hence, if the
former proportion is the true one, in giving an amount of Hydragogin
which ensures the full therapeutic effect of the digitalis, one would
administer an almost certainly fatal amount of strophanthus. Whatever
the proportion of strophanthus may be, however, the administration
of a mixture of digitalis and strophanthus in fixed proportions is
indefensible. At times it is advisable to follow one of these drugs
with the other in the treatment of cardiac disease. The simultaneous
administration of the two continuously in fixed proportions, however,
is injudicious, because of the great difference between their rates of
absorption and in their activity after they enter the blood stream. The
action of digitalis, moreover, persists much longer than does that of
strophanthus.
An advertising circular contains the following claim:
“The well-known diuretic properties of digitalis, strophanthus and
squills are greatly enhanced by the addition of the oxysaponin.”
This is not true. Saponins are not synergistic with digitalis
therapeutically; on the contrary, they exert a purely deleterious
action on the heart when they enter the circulation.
The symptoms of cardiac disease are often difficult to distinguish
from the toxic actions of the digitalis bodies. Since these bodies
must often be given to the point of beginning toxic action in order
to induce the full therapeutic effects, it is obvious that the
administration of a mixture of digitalis, strophanthus, saponin and
active principles of squill is especially liable to induce serious
toxic effects which cannot be distinguished from the symptoms of the
disease.
Hydragogin is a shotgun mixture of semisecret composition; it is
marketed under a therapeutically suggestive name, and advertised by
means of unwarranted therapeutic claims. It is therefore in conflict
with Rules 1, 6, 8 and 10. The Council held Hydragogin ineligible for
New and Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 4,
1915._)
FILUDINE
Report of the Council on Pharmacy and Chemistry
Filudine is said to be prepared by J. L. Chatelain, Paris, and is
sold in this country by Geo. J. Wallau, Inc., New York. It is offered
as a remedy for “biliary insufficiency,” “hepatic insufficiency,”
“intestinal dyspepsia,” “all affections of the liver (diabetes,
cirrhosis, cancer, etc.),” “malaria,” “obesity” and “tuberculosis.”
No quantitative information is furnished as to the composition of the
preparation and there are noteworthy discrepancies in the various
statements regarding the ingredients. In one number of “Treatment,”
a self-styled “Review” of medical literature (actually devoted to
advertising the preparations sold by Wallau), we are told that
“This product [Filudine] is a more concentrated and potent extract
of the liver, with which is combined an extract of the spleen. The
liver and the spleen are so intimately interdependent, that the
addition of a splenary extract to the liver extract is a signal
improvement from which a synergistic action results. Thiarféine is
also added, as it helps somewhat to combat the anaemia from which
all diabetics suffer more or less.”
Thiarféine is said to be
“Thiomethylarsinate of Caffein, a new salt discovered by M.
Chatelain.”
Another circular, which gives an imposing formula for “thiarféine” or
“thiomethylarsinate of caffein,” states that
“Sulphurated methylarsinate is an arsenical preparation devoid of
all toxicity on account of the intimate joining of its composing
parts.”
And that
“Filudine can never be contraindicated.”
A statement of composition in a later number of “Treatment,” however,
says that biliary extracts are components, in addition to the liver and
spleen extracts. Moreover, thiarféine, the “new salt discovered by M.
Chatelain,” is no longer “thiomethylarsinate,” but “thiocinnamate of
caffein”; and a new formula is furnished for it.
We are told that
“Methyl-arsinate cannot be used in cases where fever is present....”
“M. Chatelain at first studied the action of thiomethylarsinate;
clinical and physiological experimentation led him, however, to
adopt thiocinnamate of caffein, of greater activity and with no
contraindications.”
Nevertheless the same absence of contraindications was urged in
favor of Filudine when it was said to contain the now discarded
thiomethylarsinate of caffein.
The following are some of the unwarranted and even absurd claims:
“Filudine restores the liver’s functions. It is to the liver what
digitalis is to the heart; it overcomes the insufficiency and
stimulates the debilitated organ.”
In malaria “it is the only true specific when associated with
quinine.”
“Filudine is ... the ideal medication for tuberculosis, conforming
as it does with the most recent researches in the therapeusis of
this affection.”
“We will not go as far as to say that Opotherapy _completely
restores_ unhealthy livers, for although the lesions of the hepatic
parenchyma may be obliterated by regeneration, the lesions of
the connective tissues are permanent, and may be observed at the
postmortem examination. The new cells, however, do not present the
same unhealthy conditions as those of the former diseased gland
which they have replaced, and the liver can therefore function
normally, so that the patient lives on; and he is satisfied with
that.”
“Therefore, while regenerating the liver with Filudine, we cleanse
it and combat its congested state with Urodonal. We cause it to
produce urea from the excess of uric acid which it contains.”
“By the judicious and harmonious combination of the beneficial
effects of Filudine and Urodonal, physicians not only possess the
means of treating by rational methods Cirrhosis of the Liver in its
various forms (which is one of the most terrible diseases which can
afflict anyone) but what is still better, _they can cure it_.”
“The liver of a person suffering from obesity being incapable
of fulfilling its functions in regard to the fatty tissues, the
rational and up-to-date method of treatment is therefore to restore
to the system, in the form of Filudine, the liver extracts which
are lacking.”
Filudine is a mixture of semisecret composition. The therapeutic
claims are manifestly unwarranted. The name is not indicative of the
composition, whatever that may be, and no rational excuse is offered
for the combination of liver and spleen extracts (with or without bile
extracts) with “thiomethylarsinate” or “thiocinnamate” of caffein.
The Council therefore held Filudine ineligible for New and Nonofficial
Remedies.--(_From The Journal A. M. A., Sept. 18, 1915._)
LACTOPEPTINE AND ELIXIR LACTOPEPTINE
Report of the Council on Pharmacy and Chemistry
Mixtures of pepsin and pancreatin are therapeutically irrational;
the two substances are not indicated in the same conditions, nor can
they act together. Under physiologic conditions, such mixtures are
chemically impossible: in a liquid medium the ingredients destroy each
other.
Lactopeptin is manufactured by the New York Pharmacal Association,
Yonkers, N. Y. It is sold under the claim that it contains, pepsin,
diastase, pancreatin, lactic acid and hydrochloric acid. This product
was among the first proprietary preparations examined by the Council on
Pharmacy and Chemistry. The report of the investigation was published
in The Journal, March 16, 1907, p. 959. The preparation was found to be
practically inert--“essentially a weak saccharated pepsin,” devoid of
tryptic activity.
Six years later it was still widely advertised with the same irrational
claims. A referee (A) therefore examined Lactopeptine (powdered) for
the Council in 1913, and confirmed the previous findings. The referee’s
report was published in The Journal, Aug. 2, 1913, p. 358.
Nearly four months after this publication, the manufacturer protested
against the report, maintaining, contrary to the findings of the
Council, that Lactopeptine possesses pancreatic activity and contains
“loosely combined” hydrochloric acid. Referee A therefore repeated
his examination, and a second referee (B), independently, examined
specimens of Lactopeptine (powder) purchased on the open market for the
purpose shortly before.
A few specimens examined by these two referees showed a slight tryptic
activity; most of them showed none. The amount of hydrochloric acid
present was insignificant.
The reports of the two referees were referred to the manufacturers, who
again protested vehemently against these findings, this time on the
ground that the specimens were old. The manufacturers also cited the
work of three chemists to disprove the findings of the referees, and
demanded that the Council reexamine Lactopeptine, making use of fresh
specimens. The Council refused for the following reasons:
1. So long as the packages of Lactopeptine are not dated, the activity
of specimens known to be fresh is of no practical importance. The
activity of the actual market supply is the only question of interest
to the profession. The only fair test is that made on specimens
representative of the product sold to the ultimate consumer.
2. The evidence presented by the manufacturers did not warrant
a reexamination, since the work of two of the chemists cited
substantially corroborates the results obtained by the Council’s
referees from the fresher specimens. The figures for tryptic activity
obtained by the third chemist cited by the manufacturers could not be
accepted by the Council, since it was at variance with all other known
results of investigations of Lactopeptine.
3. As stated at the outset, whatever the tryptic activity of the
mixture, it is therapeutically useless. A demonstration of tryptic
activity in a mixture containing both pepsin and pancreatin is of
merely theoretical interest.
Such activity, of course, cannot be expected, even on theoretical
grounds, in liquid mixtures like Elixir Lactopeptine.
The Council therefore again declared Lactopeptine (powder and tablets)
and Elixir Lactopeptine ineligible for New and Nonofficial Remedies and
authorized publication of the following statement.
W. A. Puckner, Secretary
_THE COUNCIL’S REPORT_
Lactopeptine powder (New York Pharmacal Association, Yonkers, N. Y.)
was examined by the Council in 1907. At that time it was claimed to
contain
“... the five active agents of digestion--pepsin, diastase (veg.
ptyalin), pancreatin, lactic acid and hydrochloric acid--combined
in the proper proportion to insure the best results.”
The examination showed that the preparation was essentially “a weak
saccharated pepsin,” containing but small amounts of pepsin, no
hydrochloric acid, or mere traces only, and no diastase or pancreatin
(The Journal, March 16, 1907).
In 1913, the product was reexamined, because the claims, as to both
composition and therapeutic value, were still being made. Samples
were tested both of the American product, and of a British product
from John Morgan Richards & Sons, London. The original findings were
confirmed and the results were published in The Journal, Aug. 2,
1913, p. 358. Nearly four months later (November 24) the New York
Pharmacal Association wrote to the Council, objecting to the findings
and maintaining that Lactopeptine possesses pancreatic activity and
contains (“in loose chemical combination”) hydrochloric acid. In
accordance with the custom of the Council, the work was sent back for
review to the referee (A), whose conclusions were then tested by a
second referee (B), a physiologic chemist, not a member of the Council,
selected because of his special knowledge of the subject.
In December, 1913, Referee A made a large number of new tests to
determine proteolytic and amylolytic power. His results show that
the ferment activity of the preparation is so low as to merit no
recognition in practical use. The tests also show that the amount of
lactic acid or “loosely combined HCl” (or both) present is too small to
have any appreciable physiologic activity and therefore to be of any
therapeutic value.
Nine samples of Lactopeptine purchased in the open market in December,
1913, and January, 1914, were examined by Referee B early in 1914. His
studies show absence of amylase in all samples; presence of pepsin,
giving weak reactions even when compared with those of old pepsin
preparations; complete absence of trypsin in seven out of nine samples,
tryptic reaction being obtained in two samples, in one of which the
reaction, “slight at best and of no practical import,” was obtained
only after treatment for twelve hours or more.
The presence of tryptic activity in two out of the nine samples may
be due to the fresher condition of these specimens, as indicated
by the serial numbers. The evidence shows that it is a commercial
impossibility to market mixtures of pepsin, pancreatin and lactic acid
so that they can display any material tryptic activity.
It should be reaffirmed that mixtures combining peptic and pancreatic
activities are not feasible, because pepsin cannot act except in the
presence of acid, and pancreatin is destroyed by acid and by peptic
activity. Furthermore, in conditions in which pancreatin is called
for, pepsin is not, and vice versa; therefore the administration of
mixtures of pepsin and pancreatin would be unjustified, even if both
constituents could be expected to exert activity.
The foregoing observations apply to Lactopeptine in powder and tablet
form.
While mixtures of pepsin and pancreatin are unscientific and
unjustified, theoretically the two substances may coexist in a solid
preparation, and the activity of such a preparation is consequently a
proper subject of investigation. Theoretically as well as practically,
however, pepsin and pancreatin cannot exist together in solution. The
claims made for Elixir Lactopeptine and all other liquid preparations
sold as mixtures of pepsin and pancreatin are therefore impossible.
The Council has previously taken action (The Journal, Feb. 2, 1907,
p. 434) refusing to approve for inclusion with New and Nonofficial
Remedies such preparations, calling the attention of the medical
profession and of manufacturers to their worthlessness, and requesting
the American Pharmaceutical Association to instruct its committee on
the National Formulary to omit from the next edition of that work a
liquid preparation of pepsin and pancreatin recognized under the title
of “elixir digestivum compositum.”
It is recommended that the Council reaffirm this previous action,
and that Lactopeptine and Elixir Lactopeptine be declared ineligible
for New and Nonofficial Remedies because of conflict with Rule 10
(“No article will be admitted which, because of its unscientific
composition, is useless or inimical to the best interests of the public
or of the medical profession”).
Manufacturers’ Protest and Council’s Answer
The foregoing was submitted, together with the findings of the two
referees, to the manufacturers. They protested again, alleging that:
AGE OF SPECIMENS
_First._--The specimens of Lactopeptine examined by the second referee
were old. The dates of manufacture corresponding to the several batch
numbers are supplied by the manufacturers as follows:
2275 (Powder) September, 1908
2301 (Powder) June, 1909
2312 (Powder) December, 1909
2348 (Powder) October, 1911
2352 (Powder) December, 1911
2364 (Powder) July, 1912
2374 (Powder) March, 1913
2383 (Powder) October, 1913
1638 (Tablets) October, 1911
The manufacturers assert that they do not understand how specimens of
these ages could have been purchased on the open market in 1913 and
1914, inasmuch as their agents are and long have been instructed to
take up from the druggist all lots of Lactopeptine which, as indicated
by the batch numbers, have attained “any appreciable age.” The age of
the specimens, the manufacturers declare, deprives the table in the
second referee’s report of “all significance or interest.”
As previously stated, however, the specimens of Lactopeptine examined
were purchased on the open market in various localities in unbroken
packages, in December, 1913, and January, 1914. They thus represent
stock used in filling physicians’ prescriptions or sold to the
public. Neither the referees nor any one connected with the Council
had any means of knowing the age of the specimens until the dates of
manufacture were furnished by the New York Pharmacal Association. The
first tests of the second referee were made in February, 1914, on
Specimens 2374 and 2383, which were then, it would appear, about one
year old and four months old, respectively. The Council has repeatedly
urged that pharmaceutical substances which are subject to deterioration
should be dated by the manufacturer, and a similar suggestion has
been made by the Bureau of Chemistry of the U. S. Department of
Agriculture concerning mixtures containing enzymes. Notwithstanding
the instructions which the New York Pharmacal Association claims to
have given its agents, the market supply of Lactopeptine in December,
1913, and January, 1914, was not composed of new stock, and until
the manufacturers adopt the practice of dating packages, there can
be no assurance that it will be fresh. In this connection, it is of
interest to note that the Bureau of Chemistry of the U. S. Department
of Agriculture has issued a warning that it will judge such products by
the degree of their activity when they reach the consumer, i. e., as
they are found on the market.
REPORTS OF OTHER CHEMISTS
_Second._--The New York Pharmacal Association cites the work of several
chemists, who have examined Lactopeptine and report the presence of
tryptic activity. Dr. S. R. Benedict in December, 1913, reported to
the Council “distinct” tryptic activity (digestion in twelve hours by
Lactopeptine of 4.2 times its weight of fibrin containing 50 per cent.
moisture) in specimens examined by him. These specimens were numbered
2382, and were therefore probably manufactured in October, 1913;
compare the dates furnished by the manufacturer for the specimens used
by the second referee. No tests against other preparations possessing
tryptic activity are reported, and Dr. Benedict expressly disclaims
any opinion as to the therapeutic value of the preparation.[27] Dr.
P. B. Hawk, whose report was submitted by the manufacturers, found in
Lactopeptine by Fermi’s method one-fifth tryptic activity of that of
Merck’s pancreatin, and by Grützner’s method an activity of 18 per
cent. of the pancreatin. A test for the production of tryptophan was
reported positive. The New York Pharmacal Association also submitted
a report from Dr. A. W. Balch, who found pepsin, rennin, trypsin,
steapsin, amylopsin and lactic acid present in Lactopeptine; also
an amount of combined hydrochloric acid in 1 gm. the equivalent of
1.05 c.c. tenth normal solution or 0.00383 gm. hydrochloric acid. (He
reports digestion in twenty-four hours by Lactopeptine of 25 times its
own weight of fibrin. “An active extract of pancreas reacted exactly
like the Lactopeptine solution.”) The serial numbers of the specimens
tested by Hawk and Balch are not given, but no doubt they were fresh.
[27] Dr. Benedict’s personal communication to a member of the Council
is as follows:
“In the report of the Council upon Lactopeptine which you sent to me,
I find the following statement: ‘Careful examination failed to show
the presence of either diastase or pancreatin.’ In this connection
I will cite to you the following experiment carried out by myself:
A package containing a 1-ounce bottle of Lactopeptine (powder) with
seal unbroken was purchased in the open market and opened in this
laboratory. The label bore the special Number 6 2382. Two hundred
milligrams of this product was dissolved in 50 c.c. of a 0.25 per cent.
solution of sodium carbonate in water. This solution was divided into
two portions of 25 c.c. each. One of these portions was boiled at once,
and after cooling was added to 1 gm. of moist fibrin contained in a
flask. The other portion (unboiled) was also added to 1 gm. of moist
fibrin contained in a flask. Both flasks (after addition of 5 c.c.
of toluene to each) were stoppered and placed in an incubator at 37
degrees, and left there for twelve hours. Examination of the two flasks
at the end of this period showed that the one to which the unboiled
solution of Lactopeptine [powder] had been added contained much less
solid protein than did the other. Although this fact was obvious to
the naked eye, the exact extent of digestion in the two flasks was
determined by heating both to boiling, acidifying with acetic acid,
diluting to definite volume, filtering and determining the nitrogen in
the filtrate by Kjeldahl’s method. Subtracting the trace of nitrogen
contained in the filtrate of the control flask, the results showed
that 42 per cent. of the original fibrin present had been dissolved
by the unboiled Lactopeptine solution. This can be ascribed only to
tryptic activity under the conditions of this experiment. Furthermore,
this is not simply a ‘trace’ of activity, but is at least sufficiently
marked to warrant a statement that this sample showed a distinct
tryptic activity. Inasmuch as I have obtained exactly similar results
with two other samples of Lactopeptine (powder) (these being the only
ones I have examined), I am inclined to question the correctness of
the Council’s statement regarding the absence of trypsin from this
preparation. [As noted above, a fresh preparation was used.--Ed.]
“May I again add that I am making no statement regarding therapeutic
value of preparation, and that I have no opinion upon that matter one
way or the other? My work was undertaken solely out of interest to
see whether trypsin could exist in the powder (which gives a markedly
acid solution when dissolved in water). The Elixir Lactopeptine could
theoretically show no tryptic activity, nor have I found any trace of
such activity in one sample of the Elixir examined.
“In making use of any of the contents of my letters kindly include the
statement that my work upon Lactopeptine was done without remuneration
of any kind, and was done only for the scientific interest attached to
the question.”
CONCLUSIONS
The New York Pharmacal Association demanded that the referee reexamine
Lactopeptine, making use of fresh specimens. The Council held that this
was unnecessary, for the following reasons:
1. The previous finding of the Council, that specimens of Lactopeptine
found on the open market are essentially weak saccharated pepsins, is
not to be refuted by examination of fresh specimens. Even if it be
assumed that all old specimens of Lactopeptine have been withdrawn
from the market since the last purchase of specimens for the use of
the Council’s referee, there can be no assurance that the stock will
be constantly kept fresh. Unless the manufacturers date their product,
physicians cannot know that their prescriptions are filled with fresh
material. Nor is it reasonable to ask that the Council examine the
market supply of any given proprietary at a time selected by the
manufacturers.
2. Without entering into all questions of detail in the analyses,
the Council is willing to accept the reports of Drs. Benedict and
Hawk as representative of fresh Lactopeptine powder. It is therefore
unnecessary for the Council to make further experiments along this
line. The results of these two chemists in no wise contradict the
conclusions of the Council’s referees, being comparable with those
obtained by the referee on the fresher specimens used by them. The
experiments of Drs. Hawk and Benedict show a degree of tryptic
activity which, though chemically not negligible, is quite without
significance practically, even if it could be assumed that the trypsin
in the fresh Lactopeptine escaped destruction in the stomach. The
figures for tryptic activity given by Dr. Benedict do not differ
materially from those of the first referee. Those of Professor
Hawk show a tryptic activity of from 18 to 20 per cent. of that of
commercial pancreatin--and commercial pancreatins ordinarily are of
low tryptic activity, if not inert (see Long and Muhleman: _Arch.
Int. Med._, February, 1914, p. 314.) The reports of these chemists
present no reason for changing the conclusion that “it is a commercial
impossibility to market mixtures of pepsin, pancreatin and lactic acid
so that they can display any material tryptic activity.”
The results which Dr. Balch obtained in a test for tryptic activity
show a marked discrepancy with those obtained by Drs. Hawk and
Benedict, not to mention the Council’s referees, and also with the
fact that only about 11 per cent. of “pancreatin” is claimed in the
published formula of Lactopeptine. The Council is unable to accept Dr.
Balch’s result for trypsin or rennin as reliable. His other results are
without significance and call for no special comment.
3. Even if tryptic activity were conceded to Lactopeptine, the
preparation, like all preparations containing pepsin and pancreatin,
would still be, as previously stated, therapeutically irrational.
The Council approved the report.
Report of Referee A
In view of the manufacturer’s reiteration of the claims for
Lactopeptine powder, I have carried out further experiments to
determine its proteolytic and amylolytic power.
For the proteolytic test I used fresh, well washed fibrin and examined
samples of Lactopeptine powder numbered as follows:
No. 1. A part of the English product examined and reported on last
spring.
No. 2.--A fresh bottle obtained at a Chicago retail drug store in
December, 1913.
No. 3. A fresh bottle obtained at a Chicago retail store in December,
1913.
Portions of 1 gm. each of these samples were mixed with 5 gm. fibrin,
100 mg. of sodium carbonate and 50 c.c. of water in flasks. A little
toluene was added to each flask, which was then closed with a tuft
of cotton and the mixtures were incubated at 40 degrees through
twenty-four hours. At the end of that time there was no marked change
in the quantity of the fibrin remaining in each flask, the larger part
by far being undigested.
As a control I used the sample of an active commercial trypsin, of
which I added 500 mg. to the same quantity of water, fibrin and sodium
carbonate. This was digested in the same bath at the same time. The
digestion was practically completed in less than ten minutes, only
minute flakes of the fibrin remaining.
It is evident that the digestive power of the Lactopeptine must be
extremely low, and only a small fraction of that exhibited by a
commercially good trypsin.
In an experiment with the English sample carried out through nineteen
hours as above, using 2 gm. of fibrin and 100 mg. of ferment, it was
found by nitrogen tests on the filtrate that about 12.2 per cent.
of the protein had been brought into solution, an amount which is
practically without importance in a digestion of such duration.
To test the starch digestive power I have made a large number of
experiments. In a series just completed I mixed 1 gm. portions of
Samples 1 and 2 with water to make 100 c.c. volumes. Before making
up to the final volumes 0.5 c.c. of normal sodium hydroxid was
added to neutralize the slight acidity of the ferment as shown by
phenolphthalein.
Of these mixtures 4, 6, 8 and 10 c.c. portions were mixed with 50 c.c.
of 1 per cent. starch paste and incubated at 40 degrees to find the
colorless end-point in the starch digestion, by the iodin test.
At the end of twenty-two hours the iodin reaction was as strong as at
the beginning, indicating no appreciable starch digestion.
To the flasks in which no digestion had taken place under these
conditions, 5 mg. of a pancreas ferment was added. This gave an almost
immediate conversion to the colorless end-point. This ferment was a
sample of Holadin which had been in the laboratory about a year. The
5 mg. completed the reaction to the colorless end-point in less than
ten minutes.
In a similar test I used 2 gm. of Lactopeptine No. 3, made up to
100 c.c. with 1.2 c.c. of normal alkali. Ten and 15 c.c. portions were
incubated with 50 c.c. of 1 per cent. starch paste through twenty hours
at 40 degrees with no apparent result. The Holadin then added, 5 mg.
being used, completed the conversion in less than ten minutes.
This shows that the medium was a proper one for the test and that the
Lactopeptine must be extremely weak. No sugar tests were made because
the Lactopeptine contains milk sugar to the extent of about 60 per cent.
Similar results for both protein and starch digestives have been
obtained in a large number of experiments. These here quoted show
that the ferment activity of the preparation is so low as to merit no
recognition practically. The digestion of a few milligrams of fibrin or
starch after many hours of contact, while being perhaps scientifically
possible, is of no value when we come to a consideration of the use of
such bodies as digestive ferments in medicine.
The amount of lactic acid or “loosely combined HCl” present in
Lactopeptine is very small, since the total acid which may be titrated
by sodium hydroxid and phenolphthalein is measured by 0.5 c.c. of
the normal hydroxid for 1 gm. of the Lactopeptine powder, in the
mean. In different samples examined the range was found to be from
0.41 c.c. to 0.6 c.c. Tests with methyl orange, methyl red and other
indicators showed that the free acidity is but trifling; if the whole
of this acid, as measured by phenolphthalein, were calculated to HCl,
the amount would be too small to have any appreciable physiologic
activity, in view of the daily dose recommended, 10 to 20 grains of the
powder.
Report of Referee B
The following table gives a summary of the results of my investigations
on Lactopeptine. The numbers in the extreme left-hand column are the
manufacturer’s identifying marks. These, it is assumed, run serially,
the higher numbers indicating fresher specimens.
TABLE SHOWING ENZYMIC POWER OF LACTOPEPTINE PREPARATIONS
Amylase Pepsin Rennin Trypsin Lipase
2275 - + + - -
2301 - + + - -
2312 - + + - -
2348 - + + - -
2352 - + + - -
2364 - + + +(?) -
2374 - + + - +(?)
2383 - + + + +(?)
1638 (tablets) - + + - -
Pancreatin (Old) - .. .. ++ -
The conclusions in the foregoing summary depend on the following
criteria:
_Amylase_: removal of starch (paste), _small in proportion to begin
with_.
_Pepsin_: solution of small shreds of _fresh_ fibrin in acid media.
_Rennin_: curdling of milk in moderate excess.
_Trypsin_: solution of small shreds of _fresh_ fibrin in neutral and
alkaline media, and tryptophan test.
_Lipase_: coloration of litmus-milk; exact _color_ controls.
All tests were suitably controlled. The responses for pepsin were weak
even when compared with those of old pepsin preparations.
In the table above, the interrogation points in parentheses (?) refer
to results that were obtained after treatment for from twelve to
twenty-four hours and indicates that the change was slight at best and
of no practical import.--(_From The Journal A. M. A., Oct. 23, 1915,
with additions._)
IODUM-MILLER AND IOD-IZD-OIL (MILLER’S)
Report of the Council on Pharmacy and Chemistry
The Council adopted the following report and authorized its publication.
W. A. Puckner, Secretary.
A referee has submitted to the Council the following report of the
Chemical Laboratory of the American Medical Association on Iodum-Miller
and Iod-Izd-Oil (Miller’s) (Iodum-Miller Co., Kansas City, Mo.):
The unsatisfactory statements made in regard to the composition of
Iodum-Miller and the far-reaching therapeutic recommendations for
it induced the laboratory to make a chemical examination of the
preparation. It claimed more or less directly that the preparation is
entirely new and possesses novel characteristics.
It is asserted that
“Iodum-Miller is made from Soot Iodine, which is our own product.
This Soot Iodine is SOLUBLE IN WATER before being combined with its
base C.P. Glycerine.”
No information regarding “soot iodine” is offered and an inquiry sent
to the proprietors by a physician brought only the noncommittal reply
that “soot iodine”
“is made from Resublime [resublimed?] Iodine by a chemical process
which renders it soluble in water before being combined with its
base.”
Iodum-Miller is said to contain
“Active Free Iodine 2.2 grams per 100 c.c., 10. grains per fluid
ounce, 1.7% by weight.”
“In addition to the active free iodine ... IODUM-MILLER carries a
still greater per cent of Iodine in its basic combination....”
According to the label, the preparation is
“An Iodine for External and Internal use ... 45 drops equals 1 dr.
by weight. Each drop equals the per cent. of iodine in 1 gr. potas.
iodide.”
Iodum-Miller is a heavy, dark liquid having an odor characteristic
of ether (ethyl oxid). Qualitative tests revealed the presence of
glycerin, free iodin, iodid and potassium. The specific gravity at 25
degrees was 1.284. Direct titration with sodium thiosulphate solution
indicated the presence of 1.68 per cent. of free iodin. A determination
of the total iodin content by the Hunter method indicated 3.06 per
cent. Subtraction of the amount of free iodin found from the total
amount of iodin present, gives 1.38 per cent. combined iodin. Assuming
this to be present as potassium iodid, as appears probable from the
qualitative examination and from the quantitative determination of
potassium, 1.80 per cent. potassium iodid is indicated. From this
examination it is concluded that Iodum-Miller is, essentially,
a solution of iodin and potassium iodid in glycerin, containing
1.68 per cent. free iodin and 1.80 per cent. potassium iodid. The
examination contradicts the assumption that Iodum-Miller is either
novel in principle or new. Moreover, accepting the firm’s statement
that 45 drops weigh 1 dram (60 grains) the examination shows that one
drop equals not “the per cent. of iodine in 1 gr. potas. iodide” but
instead, the per cent. of iodin in only 1/20 grain potassium iodid. As
the statement that “Each drop equals the per cent. of iodine in 1 gr.
potas. iodide” appears on the label of the trade package, Iodum-Miller
would seem to be misbranded under the federal Food and Drugs Act.
The recommended internal dosage of Iodum-Miller (from 1/2 to 20 drops)
is equivalent to from 1/40 to 1 grain of potassium iodid. Its external
efficacy in comparison with that of other iodin preparations may be
estimated by comparing the respective free iodin contents, since the
germicidal power of combined iodid is negligible. While Iodum-Miller
contains 2.15 gm. free iodin in 100 c.c., tincture of iodin contains
7 gm. per 100 c.c. and compound solution of iodin (Lugol’s solution)
contains 5 gm. free iodin in 100 gm.
Among the advertising literature is a circular which purports to be
a “Certificate from Kansas City Testing Laboratory, by Roy Cross,
Secretary.” The “certificate” attempts to prove that Iodum-Miller is
vastly superior to the official tincture of iodin as a germicide,
asserting that “In the process of dissolving [tincture of iodin] in
water, a very large amount of the iodin is lost by precipitation....”
This is not true of the tincture of iodin which is now official,
though it is true of the tincture official in former editions of the
Pharmacopeia. The report ignores completely the widely used aqueous
solution of iodin.
Iod-Izd-Oil (Miller’s) is said to be an “Iodine Combination” made
“from the same Soluble Soot Iodine as is IODUM-MILLER.” It is said
to “liberate Free Soluble Iodine” when applied to the skin, mucous
surfaces, etc. It is further defined as “Soluble Iodine combined
with water-white Hydrocarbon Oil” and is said to liberate “Soluble
Iodine 2 per cent.” While these statements suggest that Iod-Izd-Oil
(Miller’s) contains the iodin-potassium iodid combination contained in
Iodum-Miller, analysis indicated the oil to be a simple solution of
iodin in liquid petrolatum. Quantitative determinations indicated, not
2 per cent. of iodin, as claimed, but only 0.42 per cent. and all of
this was present as free iodin.
REFEREE’S REPORT
The following therapeutic claims appear on the label of a bottle of
Iodum-Miller:
“EXTERNAL INDICATIONS
“Tuberculosis, Pneumonia, Pleurisy, Cough, Sore Throat, Pyorrhea,
Tonsilitis, Rheumatism, Spinal Irritation, Boils, Felons or any
Pain. Periostitis, Carbuncles, Fistula in Ano, Goiter, Blood
Poison, Diseases of Uterus and appendages (apply full strength on
cotton wrapped applicator), Gonorrhea, acute or chronic in both
sexes, Orchitis, Bubo, Prostatitis, Swellings, Enlarged Glands,
Etc.”
“INTERNAL INDICATIONS
“Pneumonia, Tuberculosis, Pleurisy, Typhoid Fever, Syphilis,
Catarrh of Mucous surface of Alimentary Canal, Autotoxemia,
Vomiting of Pregnancy, Rheumatism, Chronic Glandular and Organic
Affections.”
The “certificate” from the Kansas City Testing Laboratory, mentioned
above, states that Iodum-Miller was found to have a germicidal value
nineteen times greater than carbolic acid--a somewhat remarkable
finding in view of the fact that iodin dissolved by means of potassium
iodid in alcohol or water, when tried on the typhoid bacillus has
recently been found to possess only four times the germicidal value
of carbolic acid in a solution of the same strength (Maben and White:
_Chem. and Drug._, Jan. 30, 1915, p. 144). The “certificate” further
states that the test “shows available iodine as found in IODUM-MILLER
to have the greatest bactericidal power of any substance that we have
ever tested that can be used medicinally.” There is no reason to
believe that the desire to please its patrons has led the “testing
laboratory” astray from the literal truth. The laboratory’s experience
may be limited and the statement therefore entirely correct as far
as it goes. No mention, however, is made of any tests comparing the
germ-destroying power of Iodum-Miller with that of tincture of iodin,
which contains 7 per cent. free iodin, unless the casual statement that
“Iodum-Miller sterilized [the skin] more quickly” than tincture of
iodin, be taken to imply such tests. It is not clear, however, by what
means the laboratory was able to determine that there were no bacteria
left alive in the skin after application of tincture of iodin and
Iodum-Miller; no details are given of the methods used in arriving at
this conclusion.
A circular says that Iodum-Miller
“... gives the Greatest Bactericidal and Therapeutic Action,
whether used Internally, Externally, Hypodermically or
Intravenously.”
In the light of the preceding report of the Chemical Laboratory of the
Association, these claims require little comment. The laboratory has
shown that the free iodin content (and consequently the germicidal
efficiency) of Iodum-Miller is less than half that of Lugol’s solution,
and less than a third of that of the official tincture of iodin. As
for the advice to use Iodum-Miller internally in diseases ranging
from pneumonia to syphilis and from typhoid to tuberculosis, in order
to be convinced of its dangerous character, it is necessary only to
recall that this treatment is equivalent to the administration of
small doses of iodid--from 1/40 to 1 grain of potassium iodid. The
mystery being removed from the composition of Iodum-Miller, the absurd
extravagance of the claims made for it becomes manifest. The criticisms
of the Council on the recommendations for Burnham’s Soluble Iodine
(The Journal A. M. A., May 15, 1915, p. 1673) apply in almost every
particular to Iodum-Miller.
Unwarranted therapeutic claims are made for Iodum-Miller; incorrect
statements are made with regard to its composition and that of
Iod-Izd-Oil (Miller’s); and the application of a trade name to both
of these products is unjustifiable, since neither is original. It is
therefore recommended that Iodum-Miller and Iod-Izd-Oil (Miller’s) be
held ineligible for New and Nonofficial Remedies--(_Abstracted in The
Journal A. M. A., Oct. 2, 1915._)
ELIXIR IODO-BROMIDE OF CALCIUM COMP. “WITHOUT MERCURY”
AND “WITH MERCURY”
Report of the Council on Pharmacy and Chemistry
The Tilden Company, New Lebanon, N. Y., and St. Louis, Mo., sells
“Elixir Iodo-Bromide of Calcium Comp. without Mercury” and “Elixir
Iodo-Bromide of Calcium Comp. with Mercury.” The latter is said to
contain, in addition to the ingredients of the former, 1/100 grain
mercuric chlorid in each fluidram. According to the label the formula
of the elixir “without mercury” is:
“_Formula_--Salts of Iodine, Bromine, Potassium, Sodium, Calcium,
Magnesium with Stillingia, Sarsaparilla, Rumex, Dulcamara, Lappa,
Taraxacum, Menispermum.”
A recent circular declares that the elixir contains:
“... a number of the most powerful alteratives of the pharmacopeia
such as chemically pure iodin, magnesium, potassium with
sarsaparilla, stillingia, prickly ash, burdock, taraxacum, etc. ...
Each fluidounce contains seventy-two grains of the combined salts.”
The same circular also alleges that each dram of the preparation
contains:
“... the equivalent of one and one-half grains of the combined
iodids, potassium and calcium ...”
It will be observed that, (1) the two statements quoted from the
circular make no reference to bromids; (2) the statement that each
dram contains “the equivalent” of 1-1/2 grains of the combined iodids,
potassium and calcium, accounts for but 12 of the 72 grains of “the
combined salts” per fluidounce declared in the preceding quotation;
(3) the circular mentions the presence of a drug--prickly ash--not
declared on the label and, finally (4) none of the “formulas” gives the
quantities of all of the several constituents.
It is evident from these “formulas” that the Tilden Company continues
its policy of concealment and mystification as exemplified in the cases
of Hydrocyanate of Iron, Tilden (discussed in The Journal, June 19,
1909, p. 2008), Febrisol (The Journal, June 29, 1912, p. 2043) and
Respirazone (The Journal, June 14, 1913, p. 1899).
In the circular just quoted (“The Conquest of Syphilis”), all hope for
the syphilitic is declared to rest in mercury and iodin, and it is
implied that only through Elixir Iodo-Bromide of Calcium Comp. is it
possible to obtain the greatest good from these drugs.
“Were the cleansing influences of these two drugs [mercury and
iodin] unavailable to the luetic patient, he, truly, would be as
pitiable an object as the leper ...
“Modern Pharmacy has devised no better means of utilizing these
anti-syphilitics than Elixir Iodo-Bromide of Calcium Comp. (Tilden)
with or without mercury.... The Elixir, in proper dosage, acts
in specific fashion and is adapted for use in all stages of the
disease.
“In the early months ... Elixir Iodo-Bromide of Calcium Comp.
(Tilden) with mercury is a trustworthy weapon and the physician
need have no fear but that it will subjugate the disease ...
“When ... the virulent stage is passed ... Elixir Iodo-Bromide of
Calcium Comp. (Tilden) without mercury may be given the patient
with every assurance that medicine’s most aggressive measures are
being resorted to ... From time to time, up to the very end of the
time honored three years’ period of treatment, it is well to put
the patient back on the bichloride, using for this purpose the form
of the Elixir administered in the first stages of the disease ...
“This regime ... will indubitably antidote the virus of syphilis
and eradicate from the organism its every vestige.”
While it seems incredible that any physician would jeopardize the
health--even the life--of a patient by accepting this boastful
magniloquence as sound therapeutic advice, still the fact that certain
medical journals lend their advertising pages to advertisements for
Tilden’s Elixir with the caption “The Conquest of Syphilis” makes it
incumbent on the Council to record its condemnation of the employment
of this unscientific, semisecret mixture.
It is recommended that Elixir Iodo-Bromide of Calcium Comp. “without
mercury” and “with mercury” be held in conflict with Rule 1 (secrecy
of composition), Rule 6 (unwarranted therapeutic claims) and Rule 10
(unscientific composition).--(_From The Journal A. M. A., Nov. 6,
1915._)
LECITHIN PREPARATIONS OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report was sent to the manufacturers of the various
lecithin preparations mentioned therein. As the replies of the
manufacturers were obviously written from the commercial point of
view and did not affect the Council’s conclusion that lecithin, when
indicated, would be given more advantageously in the form of yolk of
egg than in the less pure manufactured product, the Council directed
that the report be published, together with extracts from the replies
of the manufacturers.
W. A. Puckner, Secretary.
Commercial lecithin preparations are at best very impure substances;
all are more or less altered from the original composition. Even
with great care, the methods of extraction and drying always produce
considerable decomposition; and in some cases the phosphorus and
nitrogen contents bear but little relation to the theoretical values.
(Long, J. H.: _Jour. Am. Chem. Soc._, xxx, 881. McLean, Hugh: _Chem.
Abstracts_, May 20, 1915). There is not the slightest reliable evidence
that commercial lecithin has any advantage over the lecithin contained
in natural foods; the weight of probability is on the other side.
The doses recommended, moreover, are absurdly small; and the amount
thus administered is without practical value. Why administer a few
milligrams of a more or less decomposed lecithin when it is possible to
give a far larger weight of a purer substance in the form of yolk of
egg?
In view of these considerations the Council voted that the following
proprietary products be omitted from the next edition of N. N. R.:
Glycerole of Lecithin
Lecibrin
Lecithin Solution
Lecithol
Neuro-Lecithin-Abbott
and that the general article on “Lecithin Preparations” be transferred
to the annual Council Reports as a matter of record.
The report was submitted to the manufacturers. Their replies were
evidently based on commercial consideration, and called for no
modification in the report.
The referee recommended that the preceding report be published together
with the following extracts from the replies of the manufacturers:
From Armour and Company:
“We are selling a good deal of Lecithol and it seems to be giving
satisfactory results in some quarters.... We shall continue to
advertise Lecithol along the lines we have employed heretofore.”
From the Abbott Laboratories:
“We can assure you of our confidence in the therapeutic value of
Neuro-Lecithin. This has been attested by the reports of favorable
results sent us by many physicians, as well as by the periodical
literature of the last few years which contains a considerable
number of very encouraging references to lecithin therapy.”
From Fairchild Bros. & Foster:
“We would like simply to say that the physician and the Council
must be aware of the circumstances and the purposes which actuated
us in placing lecithin at disposal, viz., the studies--research--of
lecithin and the properties attributed to it and which led to
inquiry for and consideration of it. The _quantities_ proposed for
medicinal use were not suggested by us; the suggestion of lecithin
in small quantities as a therapeutic agent was obviously directed
by those who proposed it.... The question whether lecithin, per se,
has therapeutic properties in contrast to lecithin as naturally
contained in food substances, is something we do not undertake
to decide. The Council, on purely theoretical grounds, decides
in the negative notwithstanding clinical experience--internal
and hypodermic--and thus would deny lecithin the status of a new
and nonofficial remedy, worthy of at least tentative progressive
clinical consideration. We can only say that we offered bona fide
lecithin and that we did not make the investigation of lecithin
a pretext for the sale of all sorts of lecithin ‘jumbles’ with
lecithin in small proportions, taking their name and making their
bid on lecithin.”
Below appears the general article which has been omitted from N. N. R.:
Lecithin Preparations
Lecithins are fat-like bodies belonging to the group of phosphatides.
They all consist of glyceryl esters containing two fatty acid radicals
and the phosphoric acid radical in which one of the residual hydrogens
is replaced by the choline group. The fatty acid may be palmitic, oleic
or stearic and various combinations are known to exist; for example,
distearyl lecithin, stearyl palmityl lecithin and so on. The commercial
lecithins usually include the closely related kephalins.
On saponification the lecithins split more or less readily into
choline, the fatty acids and glycerophosphoric acid, and by fusion with
alkali nitrate and carbonate they yield alkali phosphate. They occur,
free or in combination as lecithoproteins, most abundantly in certain
animal tissues, but there are also vegetable lecithins. The lecithins
of commerce are obtained usually from yolks of eggs or from calves’ or
sheep’s brains.
Numerous processes have been devised for the preparation of lecithin
from egg-yolk or animal tissue. From egg-yolk it may be obtained by
making an alcoholic extract and precipitating by cadmium chloride. The
precipitate is washed with alcohol and ether, mixed with 80 per cent.
alcohol and warmed with the proper amount of ammonium carbonate to
remove the cadmium. After filtering hot and concentrating the filtrate
the lecithin is thrown down by cooling to a low temperature--10 C. or
below. The precipitate is taken up in chloroform and reprecipitated by
acetone.
From tissues it is obtained by extracting with warm alcohol and ether,
concentrating the extract, precipitating with acetone and repeating the
operations.
Pure lecithin is white, but the commercial preparations are
yellowish-brown wax-like solids, which are not soluble in water but
form milky emulsions which exhibit the myeline figures under the
microscope. The solubility in cold alcohol or ether is slight, but heat
aids it. Lecithins are not soluble in acetone. They are hygroscopic and
the water mixtures undergo decomposition on standing. They darken on
exposure to air and light.
The alcoholic solution is precipitated by platinum or cadmium
chloride. It is decomposed by alkalies with the formation of choline
and trimethylamine. The ash contains phosphoric acid. The different
lecithins contain from 3.84 to 4.12 per cent. of phosphorus and 1.73 to
1.86 per cent. of nitrogen. The ratio of nitrogen to phosphorus should
be at 1 to 2.21.
Lecithin is incompatible with alkalies; it should be kept in
well-stoppered bottles and should be protected from the light.
The content of lecithin (plus kephalin) in tissues is about as follows:
Per Cent.
Egg-yolk 8 to 12
Egg-white 0.1 to 0.2
Liver 2.0 to 3.0
Kidney 2.0 to 3.6
Lung 2.0 to 3.0
Pancreas 2.0 to 3.0
_Actions and Uses._--The lecithin preparations have been recommended
in many pathologic conditions, especially in malnutrition and sexual
debility. Moderate doses are said to bring about a marked retention of
nitrogen and phosphorus, but satisfactory proof of this is lacking. It
is extremely unlikely that the small doses which have been recommended
in pill or tablet form or in emulsions can have any perceptible action,
in view of the fact that many of our natural foods contain much greater
weights of available lecithins than the medicinal doses provide. There
is no good basis for the statement that the free lecithin has a greater
food value or is more readily assimilated than is the substance as
found in eggs or tissue. The reverse proposition is much more likely
to be true, especially when it is considered that the commercial
preparations are usually somewhat altered or decomposed in the process
of separation.
_Dosage._--Given by the mouth in the form of pills, tablets or
glycero-alcoholic emulsions. The amount of actual lecithin ingested
in this way is usually small because of the doubtful purity of the
original preparation. Several doses, as commonly administered, would
be required to furnish the amount of lecithin present in a small
egg.--(_From Reports of Council on Pharmacy and Chemistry, 1915,
p. 122._)
PROPRIETARY NAMES FOR LIQUID PETROLATUM
Report of the Council on Pharmacy and Chemistry
The Council has accepted the following report and authorized its
publication.
W. A. Puckner, Secretary.
A former report of the Council (Liquid Petrolatum or “Russian Mineral
Oil,” Report Council Pharm. and Chem., The Journal, May 30, 1914,
p. 1740) called attention to the large number of concerns that were
placing on the market liquid petrolatum as a proprietary under coined
names. Since then the number of such products has increased. The
Council has been requested by several concerns to consider their
products put out under proprietary brand names.
The rules of the Council affirm that “the application of ‘trade names’
to official or established nonproprietary substances tends to confusion
and fosters many abuses.” In accordance with this general ruling,
the Council has invariably refused to countenance proprietary names
applied to liquid petrolatum. The Council holds that proprietary or
coined names for this substance are detrimental to medical progress,
since they are sure to foster the impression that the particular
product is different from liquid petrolatum. Manufacturers have been
advised that there is no objection to distinguishing their products
by the addition of their firm name or the initial representing the
firm name; for instance, “Liquid Petrolatum, A. B. and Co.” or “Liquid
Petrolatum, Smith.” The Council also believes that such designations
as “Star Liquid Petrolatum” or “Liquid Petrolatum, Anchor Brand,”
may be regarded as unobjectionable, provided that the words “Liquid
Petrolatum” are always used in connection with the brand designation
and given equal prominence.--(_From Reports of Council on Pharmacy and
Chemistry, 1915, p. 127._)
SENG
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Seng (Sultan Drug Co., St. Louis) is called by the manufacturers:
“... a palatable preparation of Panax (Ginseng) in an aromatic
vehicle.”
Regarding ginseng (_Panax quinquefolia_) the United States
Dispensatory, nineteenth edition, page 1603, says:
“The extraordinary medicinal virtues formerly ascribed to ginseng
had no other existence than in the imagination of the Chinese.
It is little more than a demulcent, and in this country is not
employed as a medicine.”
No discussion of ginseng is to be found in the more recently published
books on pharmacology, materia medica and therapeutics, evidently
because their authors agree with this estimate.
On the other hand, physicians are told through the medium of
advertisements appearing in medical journals that Seng is:
“An efficient remedy in all affections in which the
gastro-intestinal glands need stimulating.
“Exceptionally useful in atonic indigestion, malnutrition,
convalescence from the acute diseases, and all digestive disorders
characterized by deranged or depressed functions.” (_Woman’s
Medical Journal_, July, 1914.)
According to the label, Seng is indicated in “indigestion,”
“malassimilation,” “malnutrition” and “wasting diseases.” It is also
stated--though the preparation is admitted to contain 18 per cent. of
alcohol--that to give babies “ten to fifteen drops in water or milk
during feeding” is a proper procedure and that “For Colic, Flatulency,
etc., the dose for an adult or child may be repeated every half hour
until relieved.”
The following are some of the exaggerated therapeutic claims made for
this preparation of a worthless drug:
“As a result of its administration the gastro-intestinal secretions
are augmented, the digestion of food is substantially increased,
and fermentative processes are promptly overcome.”
“Seng will specifically encourage the secretion of the juices in
the entire alimentary tract ...”
The formula furnished for Seng is non-quantitative and therefore
meaningless. The preparation is exploited in a manner to encourage
its ill-advised use by the public, and exaggerated and unwarranted
therapeutic claims are made for it. The use of an inefficient or
worthless drug like ginseng, moreover, is detrimental to rational
therapeutics. The Council therefore voted that Seng be refused
recognition for conflict with Rules 1, 4, 6 and 10.--(_From Reports of
Council on Pharmacy and Chemistry, 1915, p. 129._)
FROSST’S BLAUD CAPSULES
Report of the Council on Pharmacy and Chemistry
Frosst’s Blaud Capsules and Frosst’s Blaud, Arsenic and Strychnine
Capsules were submitted to the Council by C. E. Frosst & Co., Montreal,
Canada. This firm claims, on the authority of the report of a firm of
analytical chemists, that:
“... of three leading Blaud preparations bought by us on the open
market, the iron in Frosst’s Blaud Capsules showed the highest
percentage of _Ferrous_ carbonate.”
The Chemical Laboratory of the American Medical Association found this
claim unjustified. The laboratory reported that there was no especial
difference in the ferrous iron content of the various Blaud pills found
on the market, and that among ten specimens examined, the total iron
content was the lowest in the Frosst specimen. In view of this the
Council refused recognition to Frosst’s Blaud Capsules and Frosst’s
Blaud, Arsenic and Strychnine Capsules.--(_From Reports of Council on
Pharmacy and Chemistry, 1915, p. 164._)
TYREE’S ELIXIR OF BUCHU AND HYOSCYAMUS COMPOUND
Report of the Council on Pharmacy and Chemistry
Each dessertspoonful of this preparation is said to represent
Buchu Leaves 3-1/2 grains
Uva Ursi 1-1/8 grains
Pareira Brava 1-1/8 grains
Hyoscyamus 1-1/2 grains
Hops 1-1/2 grains
Acetate Potash 7-1/2 grains
Spirits Nitre 5 grains
Alcohol 5 per cent. (by volume)”
The manufacturer, J. S. Tyree, Washington, D. C., offers this formula
to the medical profession with the following claim:
“Approximate composition made [sic] by quantitative and qualitative
analysis of the finished product.”
It is also claimed that
“An even greater advantage of Tyree’s Buchu and Hyoscyamus Compound
over other drugs, lies in the fact that every constituent of
the former is required to conform to a fixed standard of active
principle strength; hence the results derivable from it are
absolutely uniform.”
These pretentious claims of scientific accuracy look rather absurd to
chemists. Many of the substances present in buchu, hops, hyoscyamus,
uva ursi and pareira brava are also present in other drugs; hence it
would never occur to a pharmaceutical chemist to try to ascertain the
composition of such a mixture as Tyree’s Elixir by “quantitative and
qualitative analysis of the finished product,” much less to determine
the “active principle strength” of each ingredient, for no methods are
known by which this can be done.
It is claimed that, because of the care exercised in making Tyree’s
Elixir
“... the results derivable from it are absolutely uniform.”
A moment’s reflection, however, must compel any physician to attribute
this statement, on the most charitable construction, to sheer
ignorance. Of course, even a definite chemical principle, such as
quinin, does not exert uniform clinical action, for clinical conditions
vary, and accordingly the patient may or may not be cured. It is simply
preposterous to claim that the clinical results obtained from such
substances as hops, pareira brava, buchu and uva ursi are absolutely
uniform.
A peculiarly vicious claim is that the elixir renders the mucous
surfaces of the genito-urinary tract “hostile to the multiplication of
the gonococci.” Since infection with the gonococcus produces the direst
results, any claim which means in plain English that the remedy assists
in producing a cure or in preventing infection with that organism
cannot be condemned too strongly. Uva ursi, to be sure, has some slight
antiseptic action but it is devoid of any curative action in gonorrhea
and the minute amounts that are present in the Tyree elixir are of no
more protective value against gonorrheal infection than a grain of
hexamethylenamin would be.
It is further claimed that the elixir is a “specific” for “Inflammation
of the Bladder, Bright’s Disease, Renal Colic, Suppurative Nephritis,
Acute Cystitis, Urethritis, Catarrh of the Bladder [it would be
interesting to know what distinction the manufacturer draws between
‘Inflammation of the Bladder,’ ‘Cystitis’ and ‘Catarrh of the
Bladder’], Acidemia, Edema, Vesical Catarrh of Old Age, Lithemia” and
that ascites and anasarca “can be reduced greatly to the satisfaction
of the patient, and honor of the physician” by using a mixture of
Tyree’s Elixir and infusion of digitalis. Such claims as these do not
merit serious discussion, for they carry their own refutation.
It is recommended that Tyree’s Elixir of Buchu and Hyoscyamus Compound
be held in conflict with Rules 5, 6 and 10 and that publication of
this report be authorized.--(_From Reports of Council on Pharmacy and
Chemistry, 1915, p. 167._)
HYDROLEINE
Report of the Council on Pharmacy and Chemistry
Hydroleine (Charles N. Crittenton Company, New York) is a cod liver
oil emulsion said to contain 45 per cent. of cod liver oil, a trace of
salicylic acid and 18-1/2 grains of “Pancreatin, Etc.,” per ounce. The
advertising claims are based largely on the theory that cod liver oil
is “that particular fat which dietetic experience and physiological
chemistry have proved to be most digestible.” As a matter of fact,
while the superior digestibility of cod liver oil over other oils has
often been asserted, neither “dietetic experience” nor “physiological
chemistry” have “proved” this by definite observations. The Crittenton
Company claims that it is more readily split than other oils. This
is probably not true, easy emulsification of the raw oil being often
confounded with easy splitting. This latter claim, however, is offered
in justification of the name “Hydroleine,” which the Crittenton Company
interprets as “hydrated oil.” A circular wrapped around the bottle
contains the assertion that “Cod Liver Oil has long been held in high
esteem by the medical profession for the treatment of a large number of
serious diseases.” This recommendation is likely to lead the public to
place undue reliance on Hydroleine in the grave conditions mentioned.
The preparation is in conflict with the rules of the Council inasmuch
as its name does not indicate its composition, unwarranted therapeutic
claims are made for it, and the exploitation is likely to give the
public unwarranted confidence in its value. The Council therefore held
Hydroleine ineligible for New and Nonofficial Remedies.--(_From Reports
of Council on Pharmacy and Chemistry, 1915, p. 171._)
CURATIVE VACCINE, BRUSCHETTINI
Report of the Council on Pharmacy and Chemistry
Curative Vaccine, Bruschettini, manufactured by A. Bruschettini, Genoa,
Italy, is claimed to have the properties “of acting directly on the
tubercular bacillus, bringing directly into the field and determining a
hyperproduction of antibacillar and antitoxic substances.” The use of
the preparation is said to be indicated in “all forms of tuberculosis.”
A referee reported to the Council that he had examined the available
information and believed that the use of this product had no
satisfactory experimental basis. The method of preparation appears to
be based more on theoretical considerations than on experimental basis.
On the recommendation of the Committee on Serums and Vaccines the
Council voted that Curative Vaccine, Bruschettini, be not accepted
because (1) the method used for the production of the vaccine was not
satisfactorily stated; (2) the theory on which its use is based has not
been satisfactorily confirmed, and (3) the value of the product is not
upheld by satisfactory clinical evidence.
The Council’s findings, in accordance with its procedure, were sent
to the manufacturers for comment. His reply was considered by a new
referee who found that the matter presented did not warrant a revision
of the Council’s conclusions. Accordingly the Council directed
publication of its findings.--(_From Reports of Council on Pharmacy and
Chemistry, 1915, p. 176._)
STEARNS’ WINE
Report of the Council on Pharmacy and Chemistry
Frederick Stearns & Co. market a preparation known as “Stearns’ Wine,”
“Stearns’ Wine of Cod Liver Ext. with Peptonate of Iron,” and as “Vinum
Ext. Morrhuae, Stearns.” The constituents are said to be “concentrated
extract of fresh cod livers,” “Peptonate of Iron” and a “fine quality
of prime Sherry Wine” containing 18 per cent. of alcohol.
This preparation was at one time marketed through the medical
profession, but is now advertised direct to the public in typical
“patent medicine” style. The label on a recently purchased bottle of
Stearns’ Wine contains the following statements:
“STEARNS WINE is an ideal tonic for elderly people, for weak, pale
and delicate children and convalescents.
“STEARNS WINE has for many years been successfully prescribed
in the treatment of general or nervous exhaustion, anemia,
malnutrition, loss of appetite, loss of sleep, faulty circulation
and impoverished blood supply.”
The scope of the recommendations for the preparation is further
indicated in a booklet accompanying the bottle, which begins:
“STEARNS’ WINE, What It Is and Why It Is Good for You.”
The conclusion is:
“STEARNS’ WINE is a safe medicine for the young, middle-aged and
old. It is a safeguard to the family health.”
It is not necessary to discuss either these all-embracing claims as
to the therapeutic efficacy of the mixture or the fallacies presented
in favor of cod-liver extract and peptonate of iron. The Council
reaffirms the opinion that whatever therapeutic value cod liver may
have resides chiefly, if not entirely, in its fatty constituents
(The Journal, Oct. 9, 1909; Reports Council Pharm. and Chem., 1909,
p. 115). A confirmation of this opinion has recently been furnished by
the investigations of Prof. J. P. Street (The Journal A. M. A., Feb.
20, 1915, p. 638) of several cod liver cordials, one of which (Vinol)
like Stearns’ Wine, is described as a wine of cod liver extract with
peptonate of iron.
Stearns’ Wine is essentially an alcoholic stimulant. It is not “a
safe medicine for the young, middle-aged and old.” The unwarranted
therapeutic claims and the recommendations for its indiscriminate use
bring it into conflict with Rules 4 and 6. The Council voted that
Stearns’ Wine be held ineligible for inclusion in N. N. R.--(_From
Reports of Council on Pharmacy and Chemistry, 1915, p. 177._)
PROTONUCLEIN AND PROTONUCLEIN BETA
Report of the Council on Pharmacy and Chemistry
The Council had adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Protonuclein, with other products of Reed and Carnrick, was examined
by the Council in 1907 and found ineligible for admission to New and
Nonofficial Remedies. According to the patent specifications, it is
prepared “from the thyroid and thymus glands, brain (pineal glands
and pituitary body), bone-marrow, pancreas, spleen, liver, salivary
glands, Brunner’s glands, Lieberkühn’s follicles and peptic glands.”
These various glandular bodies, it is said, are dried at a temperature
below 130 F. (preferably between 100 and 110); the fat is removed by
ether, the dried glands disintegrated, the connective tissue removed
by sifting and the resulting powder coated with an ether solution of
benzoin and mixed with milk sugar. The dose is three to ten tablets (9
to 30 grains) daily.
Protonuclein Beta is said to be produced by the addition to
Protonuclein of an equal amount of nucleoplasm and protoplasm of the
spleen. The dose is from two cubes (each 5 grains) three times a day to
three cubes four times a day (30 to 60 grains daily).
Special advantages over ordinary nuclein are attributed to
Protonuclein, in which, it is claimed, certain unaltered cells remain
that are more easily assimilated by the leukocytes than are ordinary
proteins, thus leading to a multiplication of cells. In the early
advertising Protonuclein was claimed to be:
“... an exact physiological product derived from the lymphoid
structures of the body without the use of chemical agents.... So
delicate is Protonuclein that any chemical agent is liable to
disturb its cellular activity.”
After its examination of the product in 1907 (The Journal, Oct. 5,
1907, p. 1198), the Council concluded that any distinction between
the action of Protonuclein and that of ordinary nuclein was purely
speculative and highly improbable. “If the active ingredients are
really so unstable that they are destroyed by all chemical agents, as
claimed, it seems impossible that the activity would be preserved when
Protonuclein is given by mouth and therefore subjected to the very
profound changes of digestion.”
At that time the importance of thyroid as an ingredient had not been
emphasized. The following year, however, Hunt and Seidell (The Journal
A. M. A., Oct. 24, 1908) reported the results of an investigation
which showed that Protonuclein was a diluted thyroid preparation, as
skilfully disguised as in the antifats Rengo and Marmola. Hunt later
pointed out (The Journal, Feb. 1, 1913, p. 384) that the amount of
nuclein contained in a dose of Protonuclein probably would not have the
slightest effect, especially when given by mouth.
The following are extracts from the Protonuclein advertising matter:
“For cancer, infectious fevers (measles, scarlet fever, typhoid and
septicaemia) and as a prophylactic.”
“Protonuclein: An ideal prophylactic for all infectious Diseases.”
“A true alterative and tissue builder.”
“The value of Protonuclein depends upon its ability to increase
cell power and promote tissue strength. It is therefore needed
whenever the organism is below the normal standard, more especially
in Anaemia, Typhoid, Neoplasms and as a Prophylactic.”
All the foregoing claims and recommendations are supposed to be based
on certain alleged discoveries which the Council has previously
characterized as “a tissue of vague speculations ... in direct conflict
with the known facts of physiologic chemistry.” As for the third claim,
Hunt and Seidell have commented on the danger of recommending thyroid,
the most powerful tissue-destroying drug known, as a “tissue builder.”
Protonuclein Beta, it is said:
“... combines the reconstructive action of Protonuclein with the
action of the vital principle of the spleen, making it a distinct
product for use in all tubercular troubles, including phthisis,
localized joint affections and scrofular conditions.”
This product, according to the manufacturers, is based on the work of a
certain Dr. Bayle of Cannes, France. Dr. Bayle said that he had treated
tuberculous patients with fresh ground up spleen of hogs (25-100 grams
per day), mixed with fruit preserve or bouillon; in cases in which this
brought on gastro-intestinal disorders, extract of the spleen pulp was
administered hypodermically. Bayle reported extraordinary improvements
in the physical and mental conditions of his patients even after a few
days of this treatment; over 90 per cent. of his tuberculous patients,
according to him, improved or were cured. This applied to all types
and stages of tuberculosis in man. “With the spleen pulp treatment
tuberculous glands disappear like syphilis lesions on administration of
mercury and iodids.”
This “spleen specific” of Bayle lacks scientific foundation; Bayle’s
own cases were not adequately controlled, and no notice has been taken
of Bayle’s report by experts on tuberculosis. Hence it practically
lacks both confirmation and contradiction.
The spleen is invaded by tubercle bacilli quite as frequently as are
the kidneys and the liver; it has no special toxic action on these
bacilli. Nor is there any reason to believe that the end products of
gastric and intestinal digestion of spleen pulp, after absorption into
the blood, exert such toxic action. It cannot be assumed that these
end products indirectly aid the healing processes through improved
metabolism, for there is no evidence that they have any specific
nutritive or stimulating action after such absorption. Altogether, what
we know of the physiology and pathology of the spleen does not warrant
us in looking for a “specific” against tuberculosis in this organ.
If, however, the known facts did justify any hope that the spleen
might furnish such a specific, manufacturers would not be warranted in
exploiting or physicians in prescribing spleen products as a remedy
for tuberculosis until control experiments on animals had confirmed
the therapeutic value of these products. In a chronic disease like
tuberculosis, no conclusions that are scientifically valid can be drawn
from clinical cases until many cases have been observed for years
under suitable conditions. Right here it may be said that the clinical
“evidence” offered in favor of Protonuclein Beta is worthless. The
observations which have been reported on this product are not such as
to permit any valid final conclusions to be drawn with regard to its
value.
The rational method of proving the worth of an alleged new specific
such as this is by animal experimentation. So far as we know, neither
Dr. Bayle nor the Reed and Carnrick company has performed any such
experiments with “spleen pulp” or Protonuclein Beta; nor are we aware
that any competent investigator has done so. There is, to the best of
our knowledge, no scientific evidence on which to base the claims for
Protonuclein Beta.
The Council reaffirms its former action with regard to Protonuclein.
The objections made to Protonuclein apply with equal force to
Protonuclein Beta. In view of the lack of evidence, the claims for
Protonuclein Beta are unwarranted and the product is ineligible to
N. N. R. on account of noncompliance with Rules 1, 6 and 8.--(_From The
Journal A. M. A., Jan. 1, 1916._)
HYDROPSIN
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Hydropsin is marketed by the Ernst Bischoff Company, Inc., New York.
Its composition is thus described:
“Hydropsin is the standardized dialysate of Digitalis purpurea,
Betula alba, Scilla maritima, Juniperis communis, and Herniaria
glabra; or, stated otherwise, it is the juice of these drugs,
dialyzed and physiologically standardized.”
“Each fluid dram represents Digitalysatum 7 gtts., and 2 gtts. each
of the dialysates of Betula, Herniaria, Juniper and Scilla.”
The composition of Hydropsin must be considered essentially secret
since the amounts of the several constituent drugs in a given amount
of “dialysate” are not disclosed. The active principle of juniper is a
volatile oil which is practically insoluble in water; it is difficult
to believe that the “juice” of juniper submitted to dialysis could
contain any material amount of the active constituent. No information
is given as to the method used whereby the several dialysates are
“physiologically standardized.” It therefore remains to be proved
that the manufacturer of Hydropsin possesses any method whereby the
dialysates of juniper (Juniperis communis), birch (Betula alba,
the common European birch) and knot weed (Herniaria glabra) are so
standardized. The claim is made that:
“Herniaria has long been recognized as one of the most valuable
drugs in the treatment of dropsical affections due to cardiac
impairment.”
On the contrary, Herniaria belongs to that large class of drugs
which have been tried, found wanting and abandoned. It is a very old
remedy, and the claims made for it are an inheritance from the early
herbalists, with whom it was very popular. According to King’s American
Dispensatory, it was “principally employed to cure _hernia_ (hence its
name) and to increase the flow of urine. It was also said to increase
the flow of bile.... Internally and externally, it was praised in
_snake-bites_, and the powdered plant was employed to kill maggots
on unhealthy _sores_ of horses. It was reputed to ‘crush’ and expel
calculi from the kidneys and bladder....”
The Ernst Bischoff Company says that:
“Betula exerts both an antiseptic and stimulating influence
on the urinary passages and is particularly serviceable where
a catarrhal condition of the bladder exists. When combined
with other diuretics, as in Hydropsin, the drug affords highly
satisfactory results in the treatment of ascites, cardiac dropsy
and hydrothorax.”
Birch is another drug which has been discarded. Few textbooks on
materia medica even mention it. That it can materially affect the
action of such powerful drugs as squill and digitalis is exceedingly
doubtful.
An unwarranted implication--that in this preparation the powerful
drugs digitalis and squill have been deprived of their dangerous
qualities--is the assertion:
“Dialysis, removing all resins and colloidals, results in better
tolerance on part of sensitive patients, and in more rapid
absorption and elimination; which, in turn, means early therapeutic
effects and little or no fear of toxic accumulation.”
That removal of colloids and resins materially affects the tolerance
of these drugs is improbable. To claim that because of their removal,
there need be “little or no fear of toxic accumulation” is utterly
without warrant. The claim that one preparation containing digitalis
is less likely to produce cumulative effect than any other digitalis
preparation is contradicted by a mass of evidence.
It is claimed that Hydropsin affects “favorably all forms of dropsy
or Edema that are at all amenable to medical treatment.” There can be
no question but that squill and digitalis, or, better, either singly,
used in suitable cases, may relieve dropsical effusions; but to claim
that such a complex mixture as Hydropsin can favorably affect all
forms of dropsy that are amenable to medical treatment is on its face
unwarranted.
The claim is made that:
“By reason of its unusual potency and relative harmlessness,
Hydropsin may be employed to great advantage in all cases where it
is desirable to increase the volume of urine without injury to the
renal structures.”
On the basis of the claimed composition, the action of Hydropsin
must be essentially that of digitalis or of digitalis and squill.
Consequently, if it possesses “unusual potency,” it cannot possess
“relative harmlessness,” and vice versa. Neither digitalis nor
squill should be employed “in all cases” of nephritis, even if it is
“desirable to increase the volume of urine.”
The composition claimed for Hydropsin brands it as an irrational
mixture in which potent drugs are combined with, and more or less
covered up by, others that are obsolete and inefficient. The name,
instead of indicating its composition, suggests diseases in which it
may be thoughtlessly and indiscriminately used. The claim that the
danger of toxic or cumulative action has been removed, if accepted by
physicians, tends to uncritical use with possible disastrous results.
Hydropsin is ineligible for New and Nonofficial Remedies because of
conflict with Rules 1, 2, 6, 8 and 10.--(_From The Journal A. M. A.,
Jan. 8, 1916._)
DIGITALYSATUM
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Digitalysatum is sold in the United States by Ernst Bischoff Company,
Inc., New York. The firm claims that it is a dialysate prepared from
the juice of freshly gathered digitalis, containing all the active
principles, and representing the fresh plant weight for weight. It is
said to be standardized physiologically and to contain 12 per cent.
alcohol. Sterisol-Digitalysatum, intended for injection, appears
to be the “dialysate” without alcohol, diluted with equal parts of
physiologic sodium chlorid solution. The Council some years ago found
both products ineligible for New and Nonofficial Remedies because
of unwarranted therapeutic claims. The preparations are still being
advertised to physicians under claims which imply superiority to all
other digitalis preparations. For instance:
“Digitalysatum is the diuretic _par excellence_ in cardiac
insufficiency ...”
“Digitalysatum as a diuretic and cardiac stimulant is in a class
by itself, being quick of action, uniform in strength, and well
tolerated.”
“Digitalysatum differs from other forms of digitalis in these
respects:... Digitalysatum is free from fat, resins and colloids,
and is therefore well-borne by sensitive patients--the young and
the feeble--and is quickly absorbed and eliminated....”
The Council has elsewhere[28] expressed the conviction that tincture
of digitalis produces the full therapeutic effects of digitalis; that,
when properly made, the tincture is as stable as any liquid preparation
of digitalis now available, and that attempts to enhance the reputation
of proprietary products by exaggerating the disadvantages of the
official preparation are to be deplored. No adequate evidence is
offered of the claimed superiority of action of Digitalysatum.
[28] Report on Proprietary Digitalis Preparations, J. A. M. A., Dec. 4,
1915, p. 2024.
By implication, the claim is made that Digitalysatum is superior to
other digitalis preparations in respect to toxicity:
“Free from fat, resins and colloidals, it is always well borne and
is quickly absorbed and eliminated. No case of toxic accumulation
(faulty elimination) has ever been reported.”
That Digitalysatum is free from the dangers of toxic cumulation is
highly improbable; in fact, it is inconsistent with the statement
that the preparation contains all the constituents found in the fresh
plant. Even if instances of cumulative action have not been reported
this does not prove that such cumulative action does not occur. The
tincture of digitalis has the systemic side-effects of digitalis in no
greater degree than the various proprietary preparations. Attempts to
create the impression that Digitalysatum possesses all the virtues of
digitalis without its chief disadvantage are to be condemned as likely
to lead to incautious use of the preparation.
These exaggerated claims are in the main made indirectly, but they are
none the less inimical to sound therapy. The Council therefore declared
Digitalysatum ineligible for New and Nonofficial Remedies and voted
that this report be published.--(_From The Journal A. M. A., Jan. 8,
1916._)
SO-CALLED SECRETIN PREPARATIONS
Report of the Council on Pharmacy and Chemistry
The Council authorized the following report for publication, and voted
to endorse the work of Professor Carlson discussed therein.
W. A. Puckner, Secretary.
The Council has not accepted for inclusion in New and Nonofficial
Remedies any preparations said to contain secretin or prosecretin as
their active ingredient. A report giving the reasons for the rejection
of one (the first of the so-called secretin preparations marketed) was
published early last year;[29] an article on secretin, based on work
undertaken at the request of the Council on Pharmacy and Chemistry, is
now published.[30]
[29] Secretogen, J. A. M. A., May 1, 1915, p. 1518.
[30] Carlson, A. J.; Lebensohn, J. E., and Pearlmann, S. J.: Has
Secretin a Therapeutic Value? J. A. M. A. =66=:178 (Jan. 15) 1916.
Lest the appearance of this detailed study of secretin, after the
rejection of so-called secretin preparations, should be interpreted
(as manufacturers whose products have been rejected have endeavored to
interpret such action) as a case of first condemning a preparation and
then getting the facts, the Council’s methods, and their application
in this case, may be briefly stated. The Council maintains that,
when a manufacturer places a product on the market, the burden of
proof is on that manufacturer to show that the properties of his
product are in accordance with his claims for it. As stated in the
introduction to N. N. R., “it is ... manifestly impossible for the
Council to investigate the composition of every complex pharmaceutical
mixture, or to check thoroughly every therapeutic claim; it can give
only an unbiased judgment on the available evidence.” Acting on this
principle, the Council examined the claims made for Secretogen, an
alleged secretin product manufactured by the G. W. Carnrick Company.
The conclusion was that these claims were in absolute conflict with the
available evidence as to the action of secretin.
It is not necessary to review this subject again. It will suffice to
state that the claims made for Secretogen rest on two fundamental
propositions: (1) that deficiency of secretin (or, rather, of
prosecretin) in the intestinal mucosa is a factor in gastro-intestinal
diseases; (2) that secretin given by the mouth is absorbed and produces
increased secretion of the pancreatic and intestinal juices and of the
bile.
From an examination of the evidence available, including that
submitted by the manufacturers, the Council concluded: “1. No evidence
has been presented that the absence of secretin is a cause of
gastro-intestinal disease. 2. There is no evidence that secretin in
any form is physiologically active when administered by mouth.” That
these conclusions were justified is shown again by the review given
by Carlson of the literature, much of which was also reviewed in the
Council’s previous report.
Since the claims of the Carnrick Company were not supported by any
satisfactory evidence, no further investigation on the Council’s part
was necessary to warrant rejection of the product. The Council did
not undertake to determine, for instance, whether or not Secretogen
and similar products actually contain secretin; the determination of
this point was immaterial here, in view of the conclusiveness of the
evidence that secretin given by mouth has no physiologic action.
Since firms other than the G. W. Carnrick Company are manufacturing
alleged secretin preparations, and since recommendations for the use
of secretin preparations in gastro-intestinal diseases have even crept
into textbooks, it seemed desirable to obtain further information on
certain points. The Council therefore requested Prof. A. J. Carlson
of the University of Chicago to check the results of previous
investigators with regard to the action of secretin administered by
mouth or directly into the intestine, and, in addition, to investigate
the secretin content of certain alleged secretin preparations.
Carlson and his co-workers, like all previous investigators, found that
secretin given by mouth, or introduced even in enormous doses directly
into the intestine, is entirely inactive. They also found that marked
destruction of secretin followed contact for one minute with human
gastric juice and that secretin is rapidly oxidized and rendered inert
in contact with the air.
Further, they were unable to demonstrate the presence of secretin
in samples of Secretogen and another supposed secretin preparation
(Duodenin) bought on the open market. In the case of Secretogen there
was one exception: one bottle was found which contained a little
secretin, but it was necessary to administer (by intravenous injection,
of course) the entire contents of the bottle (100 tablets) to obtain “a
small but unmistakable secretin reaction.”
In these studies the methods employed were those by which secretin was
discovered. It is only by the use of such methods that the presence or
absence of secretin can be determined. Apparently the manufacturers who
place so-called secretin preparations on the market do not make use of
these methods, by which alone even the composition of their products
can be determined.
Carlson and his collaborators conclude:
“There is as yet no reliable evidence that lack of secretin is a
primary or important factor in any disease. Even should this be
established, secretin therapy, to be effective, must be intravenous.
Secretin has not yet been prepared in sufficiently pure state to render
possible intravenous injection in man without injurious effects. And
even when this is attained, the very fleeting action of secretin
will in all probability render secretin therapy as futile in all the
diseases in which it is theoretically indicated as epinephrin therapy
is in Addison’s disease.”
In short, secretin is as ineffective taken by mouth as it would be
rubbed on the skin.
The referee recommends that the work of Professor Carlson be
endorsed.--(_From The Journal A. M. A., Jan. 15, 1916._)
HAS SECRETIN A THERAPEUTIC VALUE?[B]
A. J. Carlson, Ph.D., J. E. Lebensohn, M.S., and S. J. Pearlman, B.S.
Chicago
[B] From the Hull Physiological Laboratory of the University of Chicago.
[B] This investigation was undertaken at the request of the Council on
Pharmacy and Chemistry. The following report, having been submitted
to the Council, received its endorsement (see preceding report of the
Council on Pharmacy and Chemistry, “So-Called Secretin Preparations”).
It is well established that acid chyme in the duodenum is the normal
stimulus to the secretion of pancreatic juice.[31] Interaction of
the acid with the duodenal mucosa liberates into the blood stream a
substance which, circulating through the pancreas, excites the latter
to activity. This exciting substance has been termed “secretin.” It
can be prepared artificially by macerating duodenojejunal mucosa in
0.4 per cent. hydrochloric acid, neutralizing the boiling mixture, and
filtering. A few cubic centimeters of the filtrate injected into a
vein produce invariably a powerful secretion of pancreatic juice.[32]
That a “chemical messenger” is at the basis of the duodenal acid
reflex has been proved by even more crucial experiments--transfusion
(Wertheimer,[33] Enriquez and Hallion[34]), cross circulation
(Fleig,[35] Matuso[36]), and perfusion of the isolated pancreas
(Huston[37]).
[31] Pawlow: The Work of the Digestive Glands, 1912.
[32] Bayliss and Starling: Jour. Physiol. =28=:325, 1902.
[33] Wertheimer: Compt. rend. Soc. de biol. =54=:475, 1902.
[34] Enriquez and Hallion: Compt. rend. Soc. de biol. =55=:233, 363,
1903.
[35] Fleig: Arch. internat. de Physiol., =10=:206, 1910.
[36] Matuso: Jour. Physiol. =45=:477, 1913.
[37] Huston: Ann. et bull. Soc. roy. de sc. méd. et nat. =70=:178, 1912.
PROPERTIES OF SECRETIN
_Prosecretin._--Secretin is soluble in water, yet a watery extract of
intestinal scrapings is without action,[32] even after being submitted
to acid treatment.[38] Starling therefore holds that secretin exists
in the intestinal mucosa in an inactive form, as “prosecretin.” The
content of the intestine in prosecretin decreases from the duodenum
down, so that one is unable to demonstrate any prosecretin in the last
2-1/2 feet of the ileum. Prosecretin is insoluble in water, acetone,
absolute alcohol or ether. Secretin, on the other hand, is readily
soluble in water, normal salt solution and diluted alcohol (70 per
cent.), but likewise insoluble in absolute alcohol and ether.
[38] Starling: Lancet, London =2=:433, 1905.
_Preparation._--All of the more dissociated acids liberate secretin
from intestinal mucosa on boiling. Their action is dependent on
the degree of dissociation,[39] carbonic and boric acids being
inactive.[40] Secretin can also be prepared with strong soaps (from
10 to 30 per cent. sodium oleate), alcohol (70 per cent.,[41] 0.6 per
cent. sodium chlorid[36]). The acid and soap in the duodenum produce
secretion; there is no necessary correspondence between the action of a
substance in the intestine and that obtained by injection after boiling
mucosa with it. The sodium chlorid, bile, maltose and glucose produce
some secretion by the latter method yet none by the former.[36] On the
other hand, ether, chloral and oil of mustard excite secretion when
in the intestine, but no secretin can be prepared from boiled mucosa
by their action. The irritation of the lining cell has produced the
necessary hydrolysis.[38] In well-controlled experiments, Wertheimer
and LePage[42] found that after the introduction of acid, secretion is
secreted into the lumen of the intestine. Matuso[36] confirmed their
results, and found this a satisfactory method for the preparation of
secretin. It is said that secretin can be obtained by merely boiling
the mucosa with water, but the results are inconstant.[43]
[39] Frouin and Lalou: Compt. rend. Soc. de biol., =71=:189, 1911.
[40] Camus: Compt. rend. Soc. de biol., 1902, =54=:442, 1902.
[41] Fleig: Jour. de physiol. et de path. gén. =6=:32, 50, 1904.
[42] Wertheimer and LePage: Jour. de physiol. et de path. gén. =4=:1061,
1070, 1902.
[43] Stepp: Jour. Physiol. =43=:441, 1912.
_Action._--Secretin is an excitant not only of the pancreatic juice
but also of the liver and the intestinal mucosa. The flow of bile is
markedly accelerated (Henri and Portier,[44] Enriquez and Hallion[45]),
likewise that of succus entericus (Delezenne and Frouin,[46] Bottazzi
and Gabrielli[47]), and intestinal peristalsis is stimulated (Enriquez
and Hallion,[48] Falloise[49]). Injections of secretin produce a marked
vasodilatation, but the secretory effect is independent of the blood
pressure changes. The pancreas is not readily fatigued by secretin.
Bayliss and Starling[50] have obtained undiminished flow after eight
hours of continuous injection. Our experience confirms this result.
Also, equal doses of secretin give corresponding results at various
intervals. Moreover, anesthesia does not affect the flow. Secretin
is unrecoverable from the glands even after two hours of continuous
injection.[51] The juice obtained by secretin has been subject to many
studies.[52] It is of high alkalinity (about seventh normal), contains
all the pancreatic ferments, and corresponds in all respects to the
juice obtained in digestion from permanent pancreatic fistulas.[53]
[44] Henri and Portier: Compt. rend. Soc. de biol. =54=:620, 1902.
[45] Enriquez and Hallion: Presse méd. =1=:105, 1903.
[46] Delezenne and Frouin: Compt. rend. Soc. de biol. =56=:319, 1904.
[47] Bottazzi and Gabrielli: Arch. internat. de physiol. =111=:156,
1905.
[48] Enriquez and Hallion: Bull. gén. de thér. =162=:202, 1911.
[49] Falloise: Bull. de l’Acad. roy. de Belgique =5=:945, 1902.
[50] Bayliss and Starling (Note 2). Matuso (Note 6). Arch. internat. de
physiol. =10=:335, 1911.
[51] Dixon and Hamill: Jour. Physiol., 1909, xxxv, 314.
[52] Bayliss and Starling: Jour. Physiol., 1904, xxx, 61. Bierry:
Compt. rend. Soc. de biol., 1907, lxii, 433. Bierry and Terroine:
Compt. rend. Acad. de sc., 1905, cxli, 146. Lalou: Comp. rend. Acad. de
sc., 1910, xxix, 824. Morel: Compt. rend. Soc. de biol., 1909, lxvii,
36. Strassano and Billoro: Compt. rend. Soc. de biol., 1902, liv, 937.
[53] Bayliss and Starling (Note 23).
_Specificity._--In a maceration of the duodenojejunal mucosa, such as
we have in secretin, the known substances are proteoses and peptones,
acid amins, bile salts, beta-imidazolethylamin, cholin, gelatin and
inorganic salts. These substances, individually and severally, together
with their derivatives, are devoid of secretory action. Chemically,
secretin, is then a specific entity. But like epinephrin, in its
distribution, it is nonspecific. Active preparations have been made
from an extraordinary variety of animals among the different classes
of vertebrates (Camus,[54] Bayliss and Starling,[55] Chapman[56]). It
is likewise found in the new-born and in the fetus.[57] Its action,
however, like its chemical composition, is markedly specific. It
stimulates the flow of pancreatic juice, bile and succus entericus.
Its effect on the gastric glands is negative, and on the saliva
likewise.[58] On the other hand, no other extracts produce pancreatic
secretion. Dr. Koch, who, in collaboration with Dr. Keeton and Dr.
Luckhardt, has done the most recent work on gastrin[59] (a substance
that most nearly resembles secretin) and has isolated an extremely
active preparation, finds that gastrin injection has likewise no effect
on the pancreas. Camus and Gley,[60] with crude preparations, had
previously obtained a similar result.
[54] Camus: Jour. de physiol. et de path. gén. =4=:998, 1902.
[55] Bayliss and Starling: Jour. Physiol. =29=:174, 1903.
[56] Chapman: Proc. Linnaean Soc., New South Wales =1=:92, 1905.
[57] Camus: Compt. rend. Soc. de biol. =61=:59, 1906. Hallion and
Lequex: Compt. rend. Soc. de biol. =61=:33, 1906.
[58] Derouaux: Arch. internat. de physiol. =3=:44, 1905. Lambert and
Myer: Compt. rend. Soc. de biol. =54=:1044, 1902. Starling: Lancet,
London =2=:501, 1905.
[59] Keeton and Koch: Am. Jour. Physiol. =37=:481, 1915.
[60] Camus and Gley: Compt. rend. Soc. de biol. =54=:648, 1902.
_Lability._--Neutral secretin is but feebly attacked by a temperature
of 100 C. If heated in an autoclave (so as to prevent oxidation), this
temperature can be continued for thirty minutes without any change
in its activity. Increasing the temperature increases the speed of
destruction, so that at 140 C. the destructive action is marked.[61]
Autoclaving at 15 pounds for fifteen minutes, as an ordinary
sterilization of culture mediums, produces, we found, a distinct though
not serious decrease in activity. Secretin acidified to fifth-normal
with hydrochloric acid loses 60 per cent. of its activity on fifteen
minutes boiling. Secretin, alkalinized to fifth-normal with sodium
hydroxid loses 95 per cent. of its activity in five minutes’ boiling;
decreases to a trace in thirty minutes, and disappears entirely in
sixty minutes. At room temperature, with fifth-normal alkalinity, 80
per cent. of secretin is destroyed in eight hours.[61] The destruction
probably means a secondary cleavage of the secretin molecule itself.
[61] Lalou (Note 21). May: Jour. Physiol. =30=:400, 1904.
Secretin is oxidized readily. If left standing uncovered for a summer’s
day, the preparation will be inactive.[51] Even if kept in the
ice-chest (no other precaution being taken), its activity is lost in
a very few days. Sunlight undoubtedly hastens the oxidative process.
If care is taken as to sterility, however, and the secretin is kept in
the ice-chest, well stoppered and in a dark flask, it will retain its
activity for several weeks.
Dixon and Hamill[51] claimed that secretin disappears quantitatively on
passage through a Berkefeld filter at 5 mm. pressure. Lalou,[62] using
higher pressure, was unable to confirm the finding, but obtained a
marked decrease in activity. Our results are in accord with those of
Lalou.
[62] Launoy: Arch. internat. de Physiol. =3=:62, 1906. Morel and
Terroine: Compt. rend. Soc. de biol. =67=:36, 1909. Zunz: Arch.
internat. de physiol. =8=:181, 1909. Lalou: Jour. de physiol.
=14=:465, 1912.
_Analogy to Epinephrin._--The analogy of secretin to epinephrin
does not generally receive enough emphasis. Both substances are
nonspecific in distribution, but specific chemically, and especially
physiologically, epinephrin acting on the myoneural junctions, secretin
on intestinal digestion. They are both relatively simple substances
of low molecular weight, and subject to rapid oxidation whereby their
properties disappear. The action in both cases is very transient. They
are the two examples of what Starling calls the “acute hormones,” in
which it is essential that reaction take place immediately, and shall
disappear as soon as the exciting cause is removed.[63]
[63] Starling: Proc. Roy. Soc. Med., 8, No. 4, 1914, Therap. and Pharm.
Section, p. 29.
CLINICAL USE OF SECRETIN
_Diabetes Mellitus._--Moore, Edie and Abram[64] were the first to
suggest a therapeutic value for secretin, having obtained favorable
results with secretin administration in diabetes. They argued that the
internal secretion of the pancreas _may_ be stimulated by secretin,
and that some cases of diabetes _may_ be due to lack of this necessary
excitant. Owing to the importance of the question, their announcement
was followed quickly by numerous investigations by other observers.
Previously, Spriggs, at the suggestion of Starling, had tried
intravenous injections of secretin free from depressor substance in a
diabetic patient, and had obtained negative results. Moore, Edie and
Abram gave their secretin by mouth over long periods. Of the five cases
cited in their first paper, two were negative. The third was that of a
man, aged 25, who received daily 30 c.c. of secretin. After a latent
period of three weeks, the sugar suddenly fell, and after four months
the urine was sugar-free. Six months later a relapse occurred with the
development of phthisis and death. The other two patients were a boy,
aged 7, and a girl, aged 9, whose urine in from three to five weeks
became sugar free during the secretin treatment in spite of severe
diabetes. One of these patients later relapsed.[65] Bainbridge and
Beddard[66] gave secretin a thorough trial in three cases with negative
results, and are disposed to attribute the results of Moore to dieting.
Dakin and Ransom[67] cited one case, secretin being given for twelve
weeks, with negative results; Foster,[65] nine cases, all negative;
Charles,[68] three cases, all negative. Crofton,[69] however, gave
secretin a trial in one case with favorable results. Moore, Edie and
Abram, in a later paper,[70] report a large number of cases tried with
the majority of results negative, though in some cases an improvement
in the digestion, and in certain cases an increase of weight was noted.
[64] Moore, Edie and Abram: Biochem. Jour., =1=:28, 1906.
[65] Foster: Jour. Biol. Chem., =2=:297, 1906.
[66] Bainbridge and Beddard: Biochem. Jour., =1=:429, 1906.
[67] Dakin and Ransom: Jour. Biol. Chem., =2=:305, 1906.
[68] Charles: Med. Press and Cir., =133=:578, 1906.
[69] Crofton: Lancet, London, =176=:607, 1909.
[70] Moore, Edie and Abram: Biochem Jour., =3=:82, 1908.
One method of testing the basis of Moore’s theory would be by examining
the prosecretin content of the intestine in diabetics. Bainbridge and
Beddard found, in the paper referred to,[66] that from five of the
six cases of diabetics examined postmortem, little or no secretin
could be prepared; but in a subsequent report of seven cases,[71]
they found only one in which the secretin obtained was scanty. The
failure to obtain secretin in some cases they claim is probably due to
the rapid postmortem degeneration of diabetic tissue. Evans,[72] in
Starling’s laboratory, found that in dogs made recently diabetic by
total pancreatectomy, but little secretin could be obtained. Hedon and
Lisbonne,[73] and Pemberton and Sweet[74] report, on the contrary, that
the duodenum of diabetic dogs is rich in prosecretin. Bainbridge and
Beddard,[71] working on a diabetic cat, likewise found prosecretin to
be present in normal quantity.
[71] Bainbridge and Beddard: Biochem. Jour. =3=:82, 1908.
[72] Evan: Jour. Physiol. =44=:461, 1912.
[73] Hedon: Compt. rend. Soc. de biol. =74=:375, 1913.
[74] Pemberton, Ralph, and Sweet, J. E.: Further Studies on the
Influence of the Ductless Glands on the Pancreas, Arch. Int. Med., May,
1910, p. 466.
_Digestive Disturbances._--Secretin for digestive disturbance was first
used in the “acid duodenal medication” of Enriquez.[75] This consisted
in the giving of tartaric acid in thick keratin capsules, the acid not
being liberated until the duodenum was reached, where it provoked the
formation of secretin. “The secretin mechanism,” he says, “is probably
capable of pathologic disturbance as would result, for example, with
diminished acidity of chyme, disturbance of the normal motility of
the stomach or pylorus, or diminished prosecretin in the mucosa. Such
a condition would produce disturbance of the pancreatic, biliary and
intestinal secretions, and interfere with intestinal movements, with
a clinical syndrome of intestinal dyspepsia as a result, among the
chief and most constant symptoms of which would be constipation.”
“The acid duodenal medication” was submitted to wide clinical use,
and very favorable results in certain obstinate cases of constipation
were reported. In regard to “diminished prosecretin in the mucosa,”
Wentworth[76] has claimed that in infantile atrophy such is the
condition, but Sweet and Pemberton[77] have found that the difficulty
of preparing secretin from human duodenums is such as to render
Wentworth’s findings inconclusive.
[75] Enriquez: Bull. du Lab. de biol. Appliq. 2, No. 2-No. 8, 1904.
[76] Wentworth, A. H.: The Cause of Infantile Atrophy, J. A. M. A.,
July 20, 1907, p. 204.
[77] Sweet, J. E., and Pemberton, Ralph: Experimental Observations on
Secretin, Arch. Int. Med., February, 1908, p. 231.
Beveridge[78] suggests the use of secretin in (_a_) pyloric stenosis,
(_b_) pancreatic insufficiency, (_c_) hepatic stimulation and cirrhosis
of the liver (_d_) to stimulate peristalsis in colonic stasis, (_e_) in
gastro-enterostomy and short-circuiting of the intestines. He claims
to have used it in over a hundred cases with “brilliant results,”
and cites four typical histories. The G. W. Carnrick Company, which
manufactures “Secretogen,” an alleged secretin preparation, cites a
number of authorities[79] as also recommending secretin for digestive
disorders. Harrower, who is or was connected with the Carnrick Company,
in clinical journals[80] has ardently advocated the use of secretin for
a large number of maladies.
[78] Beveridge: Am. Med. =20=:255, 1914.
[79] Lockwood, G. R.: Diseases of Stomach, 1913, Chapter on Achylia.
Bassler, Anthony: Am. Jour. Gastro-Enter., 1914; Kemp, R. C.: Diseases
of Stomach, Intestine and Pancreas, 1912. Reed, Boardman: Am. Jour.
Gastro-Enter., October, 1912. Ewald (Therapie der Gegenwart, 1915,
p. 5) reports favorable results with Secretogen in one of thirteen
cases.
[80] Harrower: Pediatrics =25=:430, 1913; New York M. J. =118=:315,
1913; Arch. f. Verdauungskr. =20=:577, 1914.
PHYSIOLOGIC CONSIDERATIONS
Throughout its clinical use, secretin has been given by mouth; _but
its direct introduction into the intestine of a dog under anesthesia
in even enormous quantities is without effect_. This fact, first
observed by Bayliss and Starling,[32] was confirmed by Fleig,[81] and
Matuso,[36] and our personal experiments have convinced us of its
truth. Matuso found that ordinary secretin and that obtained from
intestinal lumen gave equally negative results. Large quantities of
active secretin, moreover, acidified to 0.2 per cent. hydrochloric
acid, and left in the ileum for fifteen minutes, were still negative.
Wertheimer and Duvillier,[82] in a previous paper on this subject,
had likewise found that acid solutions of secretin (which might be
considered more normal for the intestine than when neutral), when
introduced into the ileum gave negative or inconstant results. They
conclude that it is more likely that the pancreas does not respond to
such minimal stimuli, than that the secretin is not absorbed.
[81] Flieg: Arch. gén. de méd. =191=:1482, 1903.
[82] Wertheimer and Duvillier: Compt. rend. Soc. de biol. =68=:535,
1910.
_The destructive action of the digestive enzymes leads us to believe
that it is in inactive form that secretin is absorbed._ Like
epinephrin, it cannot pass through the digestive tract. Bayliss and
Starling state that it is destroyed by one hour’s tryptic digestion.
Lalou[62] worked with the action on secretin of pepsin, dog’s gastric
juice, pancreatic juice, succus entericus and erepsin, and found in
each case a destructive effect, even almost after mixing; and after
five minutes over 75 per cent. of the activity had disappeared.
Matuso[36] introduced 30 c.c. of active secretin into the intestine,
removed it five minutes later, and found that no activity remained.
Other methods of administration have been tried. Subcutaneous
injections are practically negative (Matuso,[36] Hallion[83])
and intrapleural injections are likewise negligible (Bayliss and
Starling[55]).
[83] Hallion: Presse méd. =20=:433, 1912.
Starling[63] finds that continued intravenous injections of secretin in
a healthy dog produces after a time severe symptoms of collapse, which,
he believes, are due to change in the intestinal mucous membrane caused
by the entry and non-neutralization of the strongly alkaline pancreatic
juice.
Intestinal digestion seems little affected in achylia gastrica
(Stockton,[84] Ehrman and Lederer,[85] Bayliss and Starling[32]). This
may be due to other secretin stimulants as fats, or to the action of
the nervous mechanisms (Meltzer[86]).
[84] Stockton: In Osier and McCrae’s Modern Medicine =3=:19, 1914.
[85] Ehrman and Lederer: Deutsch. med. Wchnschr. =35=:879, 1909.
[86] Meltzer, S. J.: The Factors of Safety in Animal Structure and
Animal Economy, J. A. M. A., Feb. 23, 1907, p. 655.
THE DESTRUCTION OF SECRETIN BY HUMAN GASTRIC JUICE
We have carried out in detail experiments on the digestive effect of
human gastric juice on secretin. Our results in every respect confirm
the findings of Lalou,[62] who worked with commercial pepsin and dog’s
gastric juice, but are even more striking because of the much superior
quality of pure human gastric juice.
_Methods._--The human gastric juice was obtained from Mr. V., the
gastric fistula case of our laboratory. The chemical and digestive
characters of his juice are discussed in a recent paper.[87] In the
different experiments, different samples of gastric juice were used.
The secretin employed was always freshly prepared. Digestion was
carried out in the incubator at 38 C. with the reaction of 0.4 per
cent. acid, and the end of the period was marked by either boiling
the mixture or (in the first two experiments) by turning the mixture
alkaline. The action of the preparation, we proved, was not influenced
by the method used. The dogs on which the preparations were tested
were prepared for carotid blood pressure, injection into the external
jugular vein, and cannula in the pancreatic duct, essentially the
methods of Bayliss and Starling[32] being employed. The preparations
were injected at body temperature after being neutralized and filtered.
Except for the addition of normal salt solution instead of gastric
juice, the control injections of secretin were submitted to exactly the
same treatment as the other preparations.
[87] Carlson: Am. Jour. Physiol. =38=:248, 1915.
_Results._--Our results are embodied in Table 1. We assured ourselves
before beginning the series that incubation of secretin with _boiled_
gastric juice produced no change. It is to be noted in the table that
each experiment is a unit complete in itself, beginning and ending
with a control injection of secretin. _Special attention is called to
the marked destruction that follows contact of human gastric juice
with secretin for merely one minute._ In Experiment 4, using 1 c.c.
of human gastric juice, the action fell to 14 drops from an original
secretion of 21; in Experiment 5, using 8 c.c. of gastric juice, the
action fell to 6 drops from an original secretion of 20. Of interest
also is the rate at which we get _complete_ destruction of secretin.
This is practically 2 hours for 2 c.c. with secretin giving originally
110 drops (Experiment 2, Fig. 1), or 30 minutes for 5 c.c. with a
secretin giving originally 53 drops (Experiment 6). These results are
practically parallel, though they were obtained with different samples
of gastric juice and in different experiments.
TABLE 1.--THE DESTRUCTION OF SECRETIN BY HUMAN GASTRIC JUICE
=====================================================================
| | Secretion of Pancreatic Juice in Drops
| +--------+--------------------------------------+--------
No. |Quan-|10 C.c.c| The Secretin After Incubation |10 C.c.
of | tity|Secretin| with Human Gastric Juice |Secretin
Exper-|of |Control +-----+------+-----+------+-----+------+Control
iment|Gas- |--Begin-| | | | | | |--End of
| tric| ning |Dig. |Secre-|Dig. |Secre-|Dig. |Secre-|Experi-
|Juice|Experi- |Time,| tion |Time,| tion |Time,| tion | ment
|Used,| ment |Hrs. |Rate |Hrs. |Rate |Hrs. |Rate |
|C.c. | | | | | | | |
------+-----+--------+-----+------+-----+------+-----+------+--------
1 | 2 | 28 |6 | 0 |4 | 0 |2 | 0 | 16
2 | 2 | 110 |2 | 7 |1-1/2| 18 |1 | 18 | 41
3 | 2 | 40 |1 | 7 | 3/4| 7 | 1/4 | 8 | 31
4 | 1 | 21 | 1/2| 11 | 1/4| 12 | 1/60| 14 | 18
5 | 8 | 20 | 1/2| 1 | 1/4| 3 | 1/60| 6 | 18
6 | 5 | 53 | 1/2| 2 | .. | .. | .. | .. | ..
------+-----+--------+-----+------+-----+------+-----+------+--------
We also tried the effect of keeping the digestive time _constant_ and
varying the amount of gastric juice employed. Increasing the quantity
of gastric juice used increases the quantity of secretin destroyed
(Table 2).
TABLE 2.--EXPERIMENT 7*
Pancreatic
Preparation Juice Drops
10 c.c. secretin 20
10 c.c. secretin digested with 0.5 c.c. gastric juice 15
10 c.c. secretin digested with 3 c.c. gastric juice 13
10 c.c. secretin digested with 10 c.c. gastric juice 8
* The digestive time was kept constant at fifteen minutes. (The gastric
juice used had been _diluted_ with stomach washings.)
The reader will observe in Table 1 that the results obtained from
the control injection of secretin at the beginning of the experiment
is uniformly greater than that obtained after several injections of
digested secretin.
In view of the established fact that equal quantities of secretin can
generally be relied on to produce results,[21] one might suggest that
the injections of the split products of secretin have inhibited to some
degree the action of the pancreas. We can submit the data in Table 3
in support of this view, showing among other things that the action of
secretin is not influenced by previous injections of inert depressor
substances, though it by the injection of the cleavage products of
secretin. (The various injections in the experiments were made at about
fifteen-minute intervals).
We have carefully analyzed the reaction in blood pressure that follows
the injection of the various preparations. We find no constant effect.
Digested secretin gives a fall in blood pressure that is at times less,
at times equal, and at other times greater (Fig. 1) than that produced
by the original preparation.
Besides the bearing that it has on _the therapeutic use of secretin_,
this destructive action of the digestive enzymes is also of prime
physiologic interest. Failure to realize it has led to misconceptions
as to the intrinsic nature of secretin.
TABLE 3.--EXPERIMENTS 8 AND 9
Pancreatic
Preparations Juice Drops
Experiment 8:
10 c.c. secretin, five injections of inert depressor substances 29
10 c.c. secretin, two injections of completely digested secretin 28
10 c.c. secretin, eight injections of inert depressor substances 16
10 c.c. secretin 16
Experiment 9:
10 c.c. secretin (control, beginning of experiment) 21
10 c.c. secretin, after thirty minutes incubation with 1 c.c.
_boiled_ gastric juice 27
10 c.c. secretin, after thirty minutes incubation with 1 c.c.
_fresh_ gastric juice 11
10 c.c. secretin (control, end of experiment) 18
The findings of Lalou, confirmed by us, explain the anomaly that has
led Delezenne[88] to put forward the antisecretin theory.
[88] Delezenne and Pozerski: Jour. de Physiol., =14=:540, 1912.
SECRETIN HAS NO ACTION WHEN GIVEN BY MOUTH
It is a constant claim that so many and complex are the factors
concerned in physiologic processes, that it is not unusual for clinical
deductions to establish themselves in the face of _a priori_ laboratory
dicta. We considered it desirable, therefore, to test the action of
secretin, orally administered, in the most direct manner, and the one
freest from possible criticism. With this in view, we performed a
series of experiments on normal unanesthetized dogs having permanent
pancreatic fistulas.
_Method._--In the operations for permanent pancreatic fistulas we
followed closely the technic developed by Pawlow,[89] and with
excellent results. The dogs maintain themselves in splendid condition
if proper care is taken. This consists in feeding them only with bread
and milk, and giving sodium bicarbonate daily. The dogs were given
this treatment in the evening so that experimental procedure might be
carried on in the day with empty stomach under constant conditions.
Freshly prepared secretin in large quantities was given by stomach
tube to these dogs, and the response of the pancreas studied and
compared with the response obtained from control preparations. The same
preparation was generally not given on consecutive days.
[89] Pawlow: Ergeb. de Physiol., O., p. 266, 1902.
TABLE 4.--DETAIL OF TYPICAL EXPERIMENTS
Dogs with pancreatic fistulas, showing that secretin given by mouth has
no action on the pancreas
===================================================================
| Rate of Secretion of Pancreatic
| Juice in C.c. per Hr.
+------------------+------------------
| Continuous | Continuous
| Secretion | Secretion
Material Fed by Stomach Tube | Before Feeding | After Feeding
|-----+------+-----+-----+------+-----
|First|Second|Third|First|Second|Third
|Hour | Hour |Hour |Hour | Hour |Hour
-----------------------------+-----+------+-----+-----+------+-----
150 c.c. active secretin, | | | | | |
slightly acid | 6.5| 3.6 | 3.9 | 20.0| 6.0 | 8.0
150 c.c. active secretin, | | | | | |
slightly alkaline | 13.0| 11.0 | 5.0 | 23.0| 26.0 | 12.0
150 c.c. secretin passed | | | | | |
through Berkefeld | 7.8| 7.5 | 7.4 | 23.0| 13.0 | 11.0
150 c.c. extract of colon | 11.6| 12.0 |11.4 | 30.0| 19.6 | 14.8
150 c.c. extract of gastric | | | | | |
mucosa | 10.0| 7.0 | 8.0 | 23.0| 7.5 | 4.0
150 c.c. extract of muscle | 6.9| 11.0 | 6.4 | 35.0| 5.0 | 7.0
150 c.c. 0.4% HCl | | | | | |
(diluted to 250 c.c.) | 6.0| 8.0 | 4.0 | 33.0| 36.0 | 17.0
-----------------------------+-----+------+-----+-----+------+-----
_Results._--We have data from six dogs with a total of seventy-six
experiments. As shown in Table 4, the administration of secretin causes
an increase in the flow of pancreatic juice, _but_ the administration
of inert substances as extracts of colon, gastric mucosa or muscle
causes a like increase. The activity of the secretin may be reduced to
a low value by exposure to sunlight, or filtering through a Berkefeld
filter, yet the response of the pancreas is not correspondingly
reduced. The secretion that occurs in the control cases, every one
will admit, is but secondary to the production of gastric juice with
its accompanying hydrochloric acid, that is, excited by virtue of the
extractives and water in the preparations. Such, we can prove, is the
only action of secretin. A mixture of gelatin, peptone and salt water,
the chief incidental constituents of a secretin preparation, gives as
striking results as ever obtained from secretin administration. Yet
the objection may be made that the response of the pancreas that is
due to the incidental constituents of secretin is maximal, and that
the secretin consequently has no opportunity to display its particular
potency. But, as inspection of the accompanying tables illustrate,
the administration of hydrochloric acid shows that the response is by
no means maximal. Let us cite a striking experiment. For three hours
before the administration of hydrochloric acid, the secretion in cubic
centimeters was respectively 29.4, 11.75 and 35.4 c.c.; for the three
hours after, respectively 88.0, 49.0 and 40.5 c.c.
[Illustration: Fig. 1.--Tracings (reduced two-thirds) showing failure
of Secretogen, Elixir Secretogen, and Duodenin to stimulate the flow of
pancreatic juice even when administered intravenously in amounts three
times greater than that recommended to be given by mouth. Dog: light
ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood
pressure; _b_, flow of pancreatic juice in drops; _c_, signal showing
where the intravenous injections were made. Tracing A: Reading from
left to right, the five intravenous injections are: (1) three tablets
of Secretogen digested with 15 c.c. 0.4 per cent. hydrochloric acid
and neutralized; (2) three tablets of Secretogen boiled in 15 c.c.
0.4 per cent. hydrochloric acid and neutralized; (3) three tablets of
Secretogen in 15 c.c. 0.9 per cent. sodium chlorid; (4) three tablets
of Secretogen in 15 c.c. of 70 per cent. alcohol; (5) 15 c.c. Elixir
Secretogen. Tracing B: reading from left to right, the four intravenous
injections are: (1) 5 c.c. secretin made fresh from dog’s duodenal
mucosa; (2) three tablets of Duodenin digested in 15 c.c. 0.4 per cent.
hydrochloric acid and neutralized; (3) three tablets of Duodenin boiled
in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (4) three
tablets of Duodenin in 15 c.c. sodium chlorid (0.9 per cent.).]
TABLE 5.--SUMMARY OF EXPERIMENTS
Dogs with pancreatic fistula, weight 14 kg. Secretin given by mouth
====================================================================
| |Rate of Secretion|
| | of Pancreatic |
| | Juice in |
No. of | | C.c. Per Hour |Increase
Experi-| Material Fed +--------+--------+ in
ment | | Three | Three | C.c.
| | Hours | Hours |
| | Before | After |
| |Feeding |Feeding |
-------+---------------------------------+--------+--------+--------
3 |Secretin slightly acid | 5 | 11 | 6
5 |Secretin slightly alkaline | 24 | 30 | 6
4 |Secretin passed through Berkefeld| 18 | 23 | 5
1 |Secretin exposed to sun for 4 hrs| 16 | 29 | 13
2 |Extract of colon (rabbit) | 19 | 29 | 10
3 |Extract of gastric mucosa | 14 | 23 | 9
3 |Extract of muscle | 8 | 16 | 8
2 |Mixture of gelatin, peptone and | 23 | 33 | 10
| salt | | |
1 |1 per cent. peptone solution | 6 | 8 | 2
4 |0.2 per cent. hydrochloric acid | 13 | 37 | 24
3 |Milk and bread | 7 | 20 | 13
-------+---------------------------------+--------+--------+--------
It is possible by large doses of sodium bicarbonate given shortly
before the administration of a preparation so to depress the stomach
that it does not respond with the usual production of hydrochloric
acid. Under these conditions the administration of secretin is
uniformly negative, but the administration of hydrochloric acid on the
contrary still serves to increase the pancreatic secretion (Table 6).
TABLE 6.--SECRETIN IN EXPERIMENTAL “ACHYLIA GASTRICA”
====+=================================================================
| | Rate of Secretion of Pancreatic Juice
| | in C.c. Per Hour
| +--------------------+-------------------
Exp.| Material Fed |Continuous Secretion| Secretion After
No. | | Before Feeding* | Feeding
| +------+------+------+------+------+-----
| |First |Second|Third |First |Second|Third
----+------------------------+------+------+------+------+------+-----
1 |} {| 8.7 | 7.5 | 6.8 | 3.0 | 1.0 | 4.8
2 |} 150 c.c. secretin {| 4.5 | 6.5 | 10.0 | 6.0 | 7.5 | 7.6
3 |} {| 15.6 | 8.1 | 16.0 | 3.9 | 4.9 | 2.9
| | | | | | |
1 |} 150 c.c. 4% HCl {| 9.8 | 7.0 | 6.0 | 65.1 | 28.0 | 7.1
2 |} (diluted to 250 c.c.){| 17.4 | 18.5 | 17.0 | 34.0 | 18.0 | 20.0
----+------------------------+------+------+------+------+------+-----
* Five gm. Na HCO₃ given at beginning of each first two hours.
COMMERCIAL PREPARATIONS OF SECRETIN
_Secretogen and Elixir Secretogen._--The Carnrick Company offers
Secretogen[90] for use in a large number of conditions. The following
indications for the use of the preparation purport to be based on
clinical tests covering a period of several years: dyspepsia, and
the indigestions generally, fermentative disorders, gastric catarrh,
flatulence, nausea; pancreatic insufficiency, intestinal indigestion;
gastric secretory deficiencies, apepsia; constipation and hepatic
torpor; intestinal stasis; diarrhea; infantile diarrhea, “summer
complaint,” marasmus, inanition and malnutrition; gastric atony and
dilatation; cholecystitis and gallstones; nephritis, neurasthenia,
cachexia and cancer; epilepsy and high blood pressure. Testimonials are
presented as to results in most of these conditions.
[90] Secretogen, Report of the Council on Pharmacy and Chemistry,
J. A. M. A., May 1, p. 1518, 1915.
A quantity of “Secretogen” and “Elixir Secretogen” was bought in
the open market, and the preparations were tested on suitably
prepared dogs. The tablets were ground, thoroughly macerated with the
solvent used (water, normal salt solution, alcohol, or 0.4 per cent.
hydrochloric acid), and filtered. If hydrochloric acid was used, the
pulverized tablets were boiled with it, in the manner that secretin is
made from duodenal mucosa, and the preparations neutralized previous
to injection. The injections were made in from 15 to 20 c.c. of the
solvent. All the operations were carried on immediately before the
experiment, and as rapidly as possible, so as to avoid oxidation. The
Elixir Secretogen was injected directly, without dilution.
TABLE 7.--SUMMARY OF TYPICAL EXPERIMENTS SHOWING THE ABSENCE OF
SECRETIN IN “SECRETOGEN” AND “ELIXIR SECRETOGEN” EXCEPT IN OCCASIONAL
TESTS WHEN ADMINISTERED IN ENORMOUS DOSES
Dogs under ether anesthesia
=======================================================================
| | Secretion of Pancreatic Juice in Drops,
| Quantity of | Following Intravenous Injection
Exp.| Secretogen +--------+---------------------------+------+--------
No.| and Elixir | | Secretogen in | |
| Secretogen |Control +---------+----+-------+----+ |Control
| Used* |10 C.c. |Distilled|0.4%| 70% |0.9%|Elixir|10 C.c.
| |Secretin| Water |HCl |Alcohol|NaCl| |Secretin
----+-------------+--------+---------+----+-------+----+------+--------
1 |Secretogen, | | | | | | |
| 1 tablet; | 109 | 0 | 0 | 0 | 0 | 0 | 59
| Elixir, | | | | | | |
| 15 c.c. | | | | | | |
1 |Secretogen, | | | | | | |
| 6 tablets | ... | .. | 0 | .. | .. | .. | ..
2 |Secretogen, | | | | | | |
| 3 tablets; | 16 | 0 | 0 | 0 | 0 | 1(?)| 16
| Elixir, | | | | | | |
| 15 c.c. | | | | | | |
3 |Secretogen, | | | | | | |
| 5 tablets | ... | .. |1(?)| .. | .. | .. | ..
4 |Secretogen, | | | | | | |
| 25 tablets | 14 | .. |1(?)| .. | .. | .. | 8
5 |Secretogen, | | | | | | |
| 100 tablets | 110 | .. | .. | .. | 21 | .. | 67
6 |Secretogen, | | | | | | |
| 100 tablets;| 19 | .. | 5 | .. | 1 | 2(?)| 8
| Elixir, | | | | | | |
| 125 c.c. | | | | | | |
7 |Elixir, | | | | | | |
| 50 c.c. | ... | .. | .. | .. | .. | 1(?)| ..
----+-------------+--------+---------+----+-------+----+------+--------
* One to three tablets is (according to the label) the therapeutic dose
of Secretogen; 4 to 12 c.c. the dose of Elixir Secretogen.
_Results._--In only one case was a slight response obtained, the others
gave none. Small and large doses were equally inert (Table 7, Figs.
2, 3). The preparations, though inert, always produced a depression
in blood pressure, sometimes even greater than that caused by active
secretin. Among our many tests, one bottle was found, however, to be a
little different from the rest (Experiment 4). Its entire content, 100
tablets, had been ground and boiled in 0.9 per cent. sodium chlorid.
The extract on injection was found to have a small but unmistakable
secretin reaction, equivalent to about 2 c.c. of the control secretin
used. But repeated experiments were unable to duplicate this result.
The “Secretogen” and “Elixir Secretogen” were all supposedly fresh
preparations, the retail drug store informing us that a fresh supply
was obtained from the wholesale house each week.
Secretogen, then, contains practically no secretin, and even if it did
contain secretin, it can have no effect on the pancreas when taken by
mouth. The indications for Secretogen, therefore, are based on false
premises, and the testimonials are worthless.
[Illustration: Fig. 2.--Tracings (reduced one-half) showing no
stimulation of the pancreas by Secretogen, Elixir Secretogen, and
Duodenin, even when administered intravenously in quantities one
hundred times greater than the therapeutic dose by mouth. Dog: Light
ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood
pressure; _b_, flow of pancreatic juice in drops. Tracing A: at _x_,
intravenous injection of 10 c.c. secretin prepared from duodenal mucosa
of dog. Tracing B: at _x_, intravenous injection of 100 tablets of
Secretogen digested with 0.4 hydrochloric acid and neutralized. Tracing
C: at _x_, intravenous injection of 100 tablets of Secretogen, prepared
as in Tracing B. Tracing D: at _x_, intravenous injection of 50 c.c.
Elixir Secretogen. Tracing E: at _x_, intravenous injection of 100
tablets of Duodenin (dissolved in 0.9 per cent. sodium chlorid).]
_Duodenin._--This is a preparation manufactured by Armour & Company,
which purports to be “secretin plus enterokinase.” The claims for
this product are similar to those for Secretogen, but somewhat less
sweeping. According to the manufacturers, “Duodenin (Armour) is
recommended in the treatment of intestinal disorders where an increased
flow of pancreatic, hepatic and intestinal secretion is desired. It is
of specific value in proteid digestion on the theory that secretin and
enterokinase stimulate the pancreas and activate its secretion.”
[Illustration: Fig. 3.--Tracings (reduced one-half) showing practically
complete destruction of secretin by the gastric juice. Dog under light
ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood
pressure; _b_, record of flow of pancreatic juice in drops. Time,
twenty-five minutes. Tracing A: intravenous injection of 10 c.c.
secretin (prepared fresh from dog’s duodenal mucosa) at _x_. Tracing B:
intravenous injection (at _x_) of 10 c.c. of the same secretin as in
Tracing A, after being digested in normal human gastric juice at 37 C.
for two hours.]
We bought a quantity of Duodenin in the open market, and carried out on
this product the same series of experiments as that used in the case of
Secretogen. The results were similarly negative (Table 8).
TABLE 8.--SUMMARY OF TYPICAL EXPERIMENTS SHOWING THE ABSENCE OF
SECRETIN IN “DUODENIN”
Dogs under ether anesthesia
=================================================================
| | Secretion of Pancreatic Juice in Drops,
| | Following Intravenous Injection
Exp.| Number +--------+-------------------------------+----------
No. |Duodenin| Control| Duodenin in | Control
| Tablets| 10 C.c.+---------+------+-------+------+ 10 C.c.
| Used |Secretin|Distilled| 0.4% | 70% | 0.9% | Secretin
| | | Water | HCl |Alcohol| NaCl |
----+--------+--------+---------+------+-------+------+----------
1 | 3 | 29 | 0 | 0 | 0 | 1(?)| 28
1 | 6 | ... | .. | 1(?)| .. | .. | ..
2 | 18 | 16 | .. | 6 | .. | .. | 16
3 | 5 | 14 | .. | 0 | 0 | 0 | 8
3 | 25 | ... | .. | 1(?)| .. | .. | ..
4 | 100 | 110 | .. | 0 | .. | .. | 67
5 | 150 | 19 | .. | 0 | .. | 0 | 8
----+--------+--------+---------+------+-------+------+----------
In regard to both Secretogen and Duodenin, we assume that the
manufacturers have tried to put secretin in them, but have been unable
because they have failed, in all likelihood, to check their methods
by physiologic standardization. These firms do not give any details
as to the procedure they employed in their manufacture of secretin.
Desiccated secretin of extreme potency has been prepared by various
physiologists,[91] 1 mg. (1/64 grain) of which is active when given
intravenously. It is difficult to conceive that any of these methods
were used in the preparation of Secretogen or Duodenin.
[91] Stepp (Note 13). Dale and Laidlow: Jour. Physiol. =44=:11, 1912.
Launoy and Ochslin: Comp. rend. Soc. de biol., =74=:338, 1913.
CONCLUSIONS
1. Secretin is quickly destroyed by gastric juice and by trypsin.
2. Secretin is not absorbed in active form from the alimentary tract.
3. The presence of secretin or prosecretin cannot be demonstrated in
the commercial preparations “Secretogen,” “Elixir Secretogen” and
“Duodenin” even when the therapeutic dose of the preparations is given
intravenously. In the case of “Secretogen,” intravenous injection of
100 times the therapeutic dose reveals occasionally an insignificant
trace of secretin.
DISCUSSION OF RESULTS
It is, of course, objectionable that preparations containing no
secretin should be advertised to the medical profession as containing
this substance. The more important blunder, however, consists in the
attempt to offer such preparations for oral administration, because
even chemically pure secretin would be equally ineffective when taken
by mouth. There is as yet no reliable evidence that lack of secretin
is a primary or important factor in any disease. Even should this be
established, secretin therapy, to be effective, must be intravenous.
Secretin has not yet been prepared in sufficiently pure state to render
possible intravenous injection in man without injurious effects. And
even when this has been attained, the very fleeting action of secretin
will in all probability render secretin therapy as futile in all the
diseases in which it is theoretically indicated as epinephrin therapy
is in Addison’s disease.
But there remains the alleged favorable effect from secretin therapy
by mouth in various diseases in man. It is, perhaps, impertinent for
laboratory men to comment on these clinical results. The ordinary
“testimonials” need not be considered, but we should like to ask the
serious worker who thinks he has actually obtained good results from
secretin therapy how certain he is of the causal relation between the
giving of secretin or alleged secretin and the abatement of the disease.
When a therapeutic measure not only lacks a positive basis in
physiology and pathology but runs contrary to all the well-established
experimental facts in these fundamental medical sciences, is it too
much to ask that positive clinical findings be subjected to more than
usual critical analysis before acceptance? “_Clinical tests_,” it is
said, “covering a period of several years have proved that neither the
condition in the stomach during digestion nor those in the intestine
prevent the secretin from entering intact into the circulation.” When
we meet claims such as this, should we not scrutinize the “tests” as
well as the men who make them?
We are indebted to Dr. J. H. Moorehead for assistance in part of the
surgical work.--(_From The Journal A. M. A., Jan. 15, 1916._)
ARTICLES REFUSED RECOGNITION
Report of the Council on Pharmacy and Chemistry
Below appear abstracts of the Council’s action on articles refused
recognition which were not deemed of sufficient importance to require
lengthy reports:
Radio-Rem
The Radium Therapy Company, Schieffelin & Co., selling agents,
submitted to the Council radium emanation generators called “Radio-Rem
Outfits,” designed to generate respectively 200, 1,000, 2,000, 5,000
and 10,000 Mache units per twenty-four hours.
Those who are well informed on the subject of radium therapy are of the
opinion that the administration of small amounts of radium emanation
such as generated by certain outfits is without therapeutic value. It
has been stated that at the Radium Institute of London the minimum
preliminary dose is 185 microcuries (500,000 Mache units), and as many
as 555 microcuries (1,500,000 Mache units) are employed.
In consideration of these facts the Council voted not to accept any
radium emanation generator which produces less than 2 microcuries
of emanation during twenty-four hours. Accordingly, while accepting
Radio-Rem Outfit No. 5, claimed to produce 10,000 Mache units (3.7
microcuries) and Radio-Rem Outfit No. 4, claimed to produce 5,000 Mache
units (1.8 microcuries), the Council voted not to accept Radio-Rem
Outfit No. 3, claimed to produce 2,000 Mache units (0.74 microcurie),
Radio-Rem Outfit No. 2, claimed to produce 1,000 Mache units (0.37
microcurie), and Radio-Rem Outfit C, claimed to produce 200 Mache units
(0.07 microcurie).
This report having been submitted to Schieffelin & Co. and their reply
considered, the Council authorized publication of the report. [See also
_Reports of Council on Pharmacy and Chemistry_, 1916, p. 631.]
Olio-Phlogosis
Olio-Phlogosis, a liquid preparation to be applied externally by means
of a cotton pad, is advertised by the Mystic Chemical Company, Kansas
City, Mo., thus:
“Doctor: Don’t fail to use Olio-Phlogosis liberally for Pneumonia,
Bronchitis and Pleurisy. It works quickly. Olio-Phlogosis is as far
ahead of all medicated kaolin plasters as these plasters were ahead
of the old-time moist and soggy poultices.”
A pamphlet advises the use of Olio-Phlogosis in
“... all cases of Inflammation and Congestion, such as Pneumonia,
Bronchitis, Pleurisy, Croup, Boils, Carbuncles, Rheumatism,
Swollen Glands, Peritonitis, Ovaritis, as a Surgical Dressing,
Mamitis [Mastitis (?)] Vaginitis and Metritis (on cotton tampon
to deplete these parts), Septic Wounds, Old Ulcers, Chilblain,
Eczema, Neuralgia, Inflammation of the Eyes and Ears, Alveolar
Inflammation, Burns, Scalds, Etc.”
According to the information sent to the Council by the Mystic Chemical
Company, Olio-Phlogosis has the following composition per gallon:
Ol. Eucalyptus Gaultheria drs. 8
Ol. Abies Canadensis drs. 8
Ol. Abies Canadensis drs. 2
Ol. Thyme (white) drs. 2
Resublimated Iodin crystals grs. 32
Resorcin drs. 1
Acid Boracic C. P. drs. 2
Quinine Bisulphate drs. 4
Sodium Thiosulphate drs. 3-1/2
Glycerin C. P. q. s. ad gal. 1
A nonquantitative formula which appears on the label of a sample bottle
sent to a physician enumerates the same ingredients except the sodium
thiosulphate.
The A. M. A. Chemical Laboratory reports that no free iodin could be
detected in the preparation.
Apparently, then, Olio-Phlogosis is essentially a skin irritant applied
by means of cotton; it can be expected to be just about as effective
as the old-fashioned cotton pneumonia jacket, used in conjunction with
an aromatic skin irritant, such as camphorated oil or wintergreen or
menthol ointment. The odor may have some psychic effect, and it is
possible that some of the oily matter may be absorbed by the skin. That
such small amounts, even if absorbed, can produce any considerable
systemic effect, however, is highly improbable, and the advice that
this preparation be relied on in pneumonia, pleurisy, peritonitis,
etc., is pernicious. In the few cases of pneumonia in which heat is
indicated, the plain cotton pad will usually be found sufficient. If
the physician consider the addition of a skin irritant desirable, it is
easy to select one from the official preparations. It will be far more
rational to do so than to invoke the aid of a mystic name and a complex
formula to which the patient and his family, at least, will be led to
give unmerited credit.
The claims made for Olio-Phlogosis are unwarranted; its composition
is complex and irrational, and the nondescriptive but therapeutically
suggestive name is likely to lead to uncritical use. The Council
voted that the product be refused recognition for conflict with Rules
6, 8 and 10, and that this report be published.--(_From The Journal
A. M. A., Aug. 19, 1916._)
THE HYPOPHOSPHITE FALLACY
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
The introduction of hypophosphites into medicine was due to an
erroneous and now discarded theory as to the cause of tuberculosis of
which one Dr. J. F. Churchill of London, and later of Paris, was the
promulgator and propagandist.[92] This theory was that the so-called
“tuberculosis diathesis” was due to a deficiency of phosphorus in
the blood. Believing that the hypophosphites, while nontoxic, were
capable of further oxidation in the organism, Churchill recommended
them as the best means of supplying the supposedly lacking phosphorus.
It is now known that tuberculosis is not due to a deficiency of
phosphorus. Of more importance is the fact, now known, that little
phosphorus, if any, is assimilated from the hypophosphites--far
less than from phosphorus compounds of ordinary food.[93] There is
no justification for giving hypophosphites for the sake of their
phosphorus content. For various reasons, however--partly from force of
habit and partly because of the power of advertising--many physicians
still prescribe hypophosphite preparations, and consequently, they
are still included in the Pharmacopeia and in textbooks on materia
medica and therapeutics. They are put out in the form of “specialties”
and of proprietary preparations, and are lauded extravagantly by the
manufacturers of the latter.
[92] Churchill, J. F.: De la cause immédiate et du traitement
spécifique de la phthisie pulmonaire et des maladies tuberculeuses,
Paris, 1858.
[93] The Hypophosphite Fallacy, J. A. M. A., April 25, 1914, p. 1346.
Although the overwhelming weight of evidence was against the
probability that the hypophosphite preparations are of value as
therapeutic agents, the Council thought it well to investigate the
subject. Dr. W. McKim Marriott of Baltimore was therefore requested to
review the evidence for and against the therapeutic usefulness of the
hypophosphites and to conduct such experiments as seemed necessary. His
report has already appeared in The Journal.[94]
[94] Marriott, W. McKim: The Therapeutic Value of the Hypophosphites,
J. A. M. A., Feb. 12, 1916, p. 486.
Dr. Marriott found that nine observers (Paquelin and Joly, Vermeulen,
Boddaert, Massol and Gamel, Panzer, Delaini and Berg), who endeavored
to test the alleged utilization of the hypophosphites in the organism,
reported that there is complete, or practically complete, elimination
of hypophosphites in the urine, with little or no effect on the body.
Only one experimenter (Patta) claimed that a considerable amount
of ingested hypophosphite was retained in the body; however, he
used a method now known to be inaccurate and made obvious errors in
calculation, so that his conclusions were unwarranted.
Since the evidence was even to this extent contradictory, Marriott
performed a series of experiments. The methods of this study and
details of results are described in his paper, in which he also
discusses the experiments of some other observers. Marriott writes:
“None of the subjects of the experiment [Marriott’s] experienced
any effect whatsoever from the administration of the drug....
Almost all of the ingested hypophosphite is promptly eliminated
unchanged....
“These experiments [Forbes’] demonstrate conclusively that the
hypophosphites possess no specific value as a source of phosphorus
for the body. This is not to be wondered at in view of the fact
that 85 per cent. of the phosphorus ingested in the form of
hypophosphite is excreted unchanged, and there is no proof that
even the remaining 15 per cent. is available to the organism. It is
doubtful if there are any conditions in which the body suffers from
lack of phosphorus. Even should such conditions exist, phosphorus,
in the form that it occurs in the ordinary foods, or as phosphates,
is more efficient in supplying the deficit than hypophosphites
that must be oxidized before utilization and which are only about
15 per cent. oxidized, if at all. For example, half a glass of
milk contains more available phosphorus than three large doses of
hypophosphites of 15 grains each, as great a dosage as is usually
given.
“What, then, is the therapeutic value of hypophosphites? There is
no reliable evidence that they exert a physiologic effect; it has
not been demonstrated that they influence any pathologic process;
they are not ‘foods.’ If they are of any use, that use has never
been discovered.”
In view of the foregoing, it seemed to the Council advisable to
examine the claims under which a few of the proprietary hypophosphite
preparations are marketed. The following are representative:
FELLOWS’ SYRUP OF HYPOPHOSPHITES
No very exact information concerning the composition is furnished by
the manufacturers (Fellows Medical Mfg. Co., New York). They say that
the product
“... contains the chemically pure hypophosphites of iron, quinin,
strychnin, calcium, manganese and potassium, agreeably blended
in the form of a bland, stable syrup with a slightly alkaline
reaction....
“Each fluid drachm contains the equivalent of 1-64th of a grain of
pure strychnin.”
The Fellows’ Hypophosphites advertising furnishes something like a
barometer of the popular status of hypophosphites. In one circular
(undated, but, from certain references contained in it, presumably
issued ten or fifteen years ago) we read:
“It is an indubitable fact that the hypophosphites have earned
the distinction of having their therapeutic value more completely
established than have any other remedial agents.... it is only by
accepting the current view, which was originally advanced by Mr.
Fellows, that we can satisfactorily account for the incontestable
fact that the hypophosphites are of supreme importance in the
treatment of a very extensive variety of affections.... the
hypophosphites increase the consumption of oxygen and the
elimination of carbon dioxide. In this manner, they stimulate
nutrition and promote constructive metamorphosis.... It is
now universally conceded that the widespread utility of the
hypophosphites is due to the fact that they substantially improve
metabolic processes, thus increasing the disease-resisting capacity
of all the tissues.”
The circular, continuing, emphasizes the “incomparable
phosphorus-contributing properties” of Fellows’ Syrup, its
“extraordinary reconstructive properties” and “the magnificent results
which invariably attend its employment in the treatment of anemia,
chronic bronchitis, chlorosis, neurasthenia, mollities ossium, delayed
union of fractures, rickets, convalescence,” etc.
A circular bearing the copyright date 1914, on the other hand, admits
that:
“The theories for the favorable action of Fellows Syrup of
Hypophosphites have undergone several changes.”
The same circular further maintains, however, that:
“... the fact has never been challenged that in Fellows Syrup of
Hypophosphites we have one of the most efficient, most complete,
most all-around tonics and roborants in the materia medica.”
No attempt is made to base this assertion on the therapeutic action
of the constituents. In other words, the old theory, which formed the
basis for the popularity of Fellows’ Syrup, has been thrown overboard,
but no substitute is deemed necessary; the momentum already acquired is
apparently regarded as sufficient to insure its continued sale.
Fellows’ Syrup of Hypophosphites is a semisecret, unscientific
preparation--an affront to sound therapy--exploited by means of
extravagant and misleading statements.
SYRUPUS ROBORANS (SYRUP HYPOPHOSPHITES COMP. WITH QUININ,
STRYCHNIN AND MANGANESE)
Little information concerning this preparation seems to be furnished
at present by the manufacturers, Arthur Peter & Co., Louisville, Ky.
According to an old circular, it contains, in each fluidounce,
Grains
“Hypophos. Potass. 1-1/2
Hypophos. Manganese 1
Hypophos. Lime 1
Hypophos. Iron 1-1/2
Hypophos. Quinin 6/16
Hypophos. Strichnin 1/16
“1/128 grain Strychnia to Teaspoonful.”
Further, according to the same circular:
“The Hypophosphites are especially useful in all diseases where
there is a lack of nutrition.... They are the best of all remedies
in Rachitis, non-union of fractures, Osteomalacia and Syphilitic
Periostitis.”
As for Syrupus Roborans itself:
“This elegant preparation is ... the best general tonic and
reconstructive known.”
The unwarranted therapeutic claims formerly made for it seem to be no
longer circulated. Syrupus Roborans is an unscientific, shotgun mixture.
SCHLOTTERBECK’S SOLUTION HYPOPHOSPHITES OF LIME AND SODA (LIQ.
HYPOPHOSPHITUM, SCHLOTTERBECK’S)
The Schlotterbeck & Foss Co., Portland, Maine, the manufacturers, say
of their preparation:
“This solution contains 30 grains of the combined Hypophosphites of
Lime and Soda to the ounce. It contains No Sugar, No Acid and it is
Perfectly Neutral.”
“Indications for use.--Galactostasis, Imperfect Metabolism,
Neurasthenia, Nervous Dyspepsia, Insomnia, Convalescence,
Acetonuria, Cyclic Vomiting in Infants, Diabetes, Starvation,
Deficiency of Lime, Mother’s Teeth during Pregnancy, Dentition of
Infants, Rachitis, Furunculosis, Vomiting of Pregnancy, Obesity.”
“Migraine is often caused by conditions for which this Solution is
one of the most satisfactory remedies:”
“In Insomnia due to advancing age, it will often act as a
hypnotic....”
Of the hypophosphites the Schlotterbeck & Foss Company say:
“If ‘damning it with faint praise’ on the part of some of the
leading medical authorities, or utterly condemning it as useless,
on the part of others, would kill a medicine, the Hypophosphites
would long since have disappeared as medicinal agents. Negative
testimony in regard to the value of a drug does not settle
anything.”
Of their own preparation they say:
“When we get the results that ought to follow the administration of
Hypophosphites, we have proved that Schlotterbeck’s Solution enters
the system unchanged.”
“This Solution is primarily a blood and nerve tonic and chemical
food.”
Schlotterbeck’s Solution of Hypophosphites of Lime and Soda is a
semisecret preparation marketed under claims that are both unwarranted
and misleading.
ROBINSON’S HYPOPHOSPHITES
According to the manufacturers, the Robinson-Pettet Company,
Louisville, Ky., each fluidounce of this preparation contains:
“Hypophosphites Soda 2 gr.
Hypophosphites Lime 1-1/2 gr.
Hypophosphites Iron 1-1/2 gr.
Hypophosphites Quinin 3/4 gr.
Hypophosphites Strychnine 1/16 gr.”
It is claimed to be
“Nutritive, Tonic Alterative. A Standard Remedy in the treatment of
Pulmonary Phthisis, Bronchitis, Scrofulous Taint, General Debility,
etc. Stimulates Digestion, promotes Assimilation.”
The declared composition of the preparation is unscientific, and the
therapeutic claims are unwarranted.
EUPEPTIC HYPOPHOSPHITES
Nelson, Baker & Co., Detroit, Mich., who market Eupeptic
Hypophosphites, call this preparation:
“A superior combination containing the Hypophosphites of Potassium,
Calcium, Iron and Manganese, and the bitter tonics, Quinin and
Strychnin, agreeably associated with natural digestive ferments
of the pancreatic secretion. It is thus a general reconstructive
tonic.... The remedy is of especial value in the treatment of
mental and nervous affections.... It is indicated in pulmonary
tuberculosis, in all wasting diseases, in debilitated conditions
generally and in all exhaustion from over work.”
On the basis of the manufacturer’s statement, Eupeptic Hypophosphites
must be regarded as a semisecret, unscientific, shotgun preparation,
exploited through unwarranted therapeutic claims.
MCARTHUR’S SYRUP OF THE HYPOPHOSPHITES COMP. (LIME AND SODA)
So far as the recent literature and trade package are concerned, no
information as to the composition of this product is furnished beyond
what is conveyed in the name. The advertising for McArthur’s Syrup,
like that for Fellows’ Syrup and Peters’ Syrupus Roborans, has been
modified as time has passed. A few years ago it was advertised under
such claims as the following:
“... Has Stood the Test during many years for unequaled efficacy
in the treatment of Tuberculosis.... Indicated also as a Tonic and
Tissue Builder in convalescence from Fevers, in Nervous Diseases,
Rickets, Senile Debility and Bronchitis.”
“Its use is indicated in ... diseases of the chest, chronic cough,
throat affections, general debility, brain exhaustion, cholera
infantum and wasting diseases of children.”
At present no definite claims seem to be made for it; the manufacturers
evidently find the magic name of hypophosphites sufficient to evoke
the spell for which the advertisement writer’s aid was once sought.
A testimonial contained in a circular which seems to be still used
illustrates both the kind of aura which surrounds hypophosphites in
the minds of physicians who are still living in the past, and the kind
of logic which has made the reputation of this and many other equally
worthless preparations.
“Just about six years ago I had a severe attack of La Grippe which
almost killed me. Left me with Asthma (Catarrh) and a severe cough.
Did not get out of the house for three months. Took over a dozen
bottles McArthur’s Hypophos.--came out all right and since then
worked hard, but last Fall took another cold, but worked on, used
McArthur’s Hypophos., am using it now, am on my 12th bottle.
“I have five or six patients whom I have put on McArthur’s
Hypophos., but I do not prescribe the single bottle, but
_wholesale_ no less than half dozen bottles. One patient is on
his 24th bottle with orders to get another half dozen and keep it
up all winter. I have given the same order to all (keep it up all
winter) and I myself intend to do the same, for with its use I have
lost no time--rain or shine I am doing my work. I know what it has
done for me and what it is doing for my patients.”
It would be hard to find a more characteristic example of the naïve
mental processes of the simple folk who in all good faith write
testimonials for worthless medicines. This well-meaning practitioner
(a homeopath, by the way), because he “came out all right” after an
attack of grip, returns all praise to McArthur’s Hypophosphites, which
he has taken “wholesale.” Not the faintest doubt of the validity of
his _post hoc ergo propter hoc_ argument seems to glimmer across his
consciousness.
McArthur’s Syrup of the Hypophosphites is an irrational preparation.
While its faults are fewer and less glaring than those of some other
proprietaries, the circulation of such a testimonial as the one just
quoted is sufficient of itself to cast suspicion on the product.
BORCHERDT’S MALT OLIVE WITH HYPOPHOSPHITES, MALTZYME WITH
HYPOPHOSPHITES AND MALTINE WITH OLIVE OIL AND HYPOPHOSPHITES
These preparations are now described in the appendix to New and
Nonofficial Remedies. Borcherdt’s Malt Olive with Hypophosphites
(Borcherdt Malt Extract Company, Chicago) is said to contain in each
100 c.c., 0.64 gm. each of calcium and sodium hypophosphites, with
malt extract, olive oil and glycerine. Maltzyme with Hypophosphites
(Malt-Diastase Company, New York) is said to contain, in each
100 c.c., 0.4 gm. each of calcium, sodium and potassium hypophosphites
and 0.005 gm. each of iron and manganese hypophosphites, with
maltzyme. Maltine with Hypophosphites (Maltine Company, Brooklyn,
N. Y.) is said to contain in each 100 c.c., 0.64 gm. each of calcium
and sodium hypophosphites and 0.42 gm. of iron hypophosphite, with
maltine. Maltine with Olive Oil and Hypophosphites (Maltine Company,
Brooklyn, N. Y.) is said to contain, in each 100 c.c., 0.6 gm. each
of calcium and sodium hypophosphites, with maltine and olive oil. In
general, no therapeutic claims are made for these mixtures so far as
the hypophosphites are concerned. The addition of hypophosphites to
such mixtures is irrational and, since it tends to perpetuate the
hypophosphite fallacy, detrimental to sound therapeutics.
THE COUNCIL’S ACTION
The Council endorsed the conclusions of the work of Dr. Marriott
referred to above, and noted: (1) that the therapeutic use of
hypophosphites (except possibly in some cases as a convenient means of
administering the positive element in the salt, as ammonium in ammonium
hypophosphite or calcium in calcium hypophosphite) is irrational; (2)
that the merits of each hypophosphite salt submitted for consideration
under the foregoing exception must be judged individually, and (3)
that Fellows’ Syrup of Hypophosphites, Peters’ Syrupus Roborans,
Schlotterbeck’s Solution Hypophosphites of Lime and Soda, Robinson’s
Hypophosphites, the Eupeptic Hypophosphites of Nelson, Baker &
Co., and McArthur’s Syrup of the Hypophosphites are ineligible for
inclusion in New and Nonofficial Remedies, and that Borcherdt’s Malt
Olive with Hypophosphites, Maltzyme with Hypophosphites, Maltine
with Hypophosphites, and Maltine with Olive Oil and Hypophosphites
be deleted from the appendix of N. N. R. Of these preparations,
all are in conflict with Rule 10; Fellows’ Syrup, Schlotterbeck’s
Solution, Robinson’s Hypophosphites and Nelson, Baker & Co.’s Eupeptic
Hypophosphites are in conflict with Rule 6; the Fellows, Schlotterbeck,
and Nelson, Baker preparations are also in conflict with Rule
1.--(_From The Journal A. M. A., Sept. 2, 1916._)
PULVOIDS CALCYLATES
Report of the Council on Pharmacy and Chemistry
Pulvoids Calcylates 5 grains was submitted by the Drug Products
Company, Inc., New York, under the following claims as to composition:
“When ingested represents the following chemical formulas:
OH)
C₆H₄ COO)₂ Ca.2H₂O + Sr.(C₇H₅O₃)₂ + 2H₂O.”
“Strontium Di-Salicylate 2-1/2 grs. and our especially prepared
Salt of Calcium and Acid Salicylic adjusted in such nascent form,
that these pulvoids upon ingestion will promptly form Calcium
Neutral Di-Salicylate 2-1/2 gr.”
“A combination of Calcium and Strontium Di-Salicylate, in seemingly
true chemical union.”
These statements are rather vague, possibly because they are an attempt
to mystify. The product, however, may be assumed to be a mixture (not a
chemical combination) of calcium salicylate and strontium salicylate.
The therapeutic claims made for the preparation are:
“Superior to ordinary salicylates. Can be taken continuously
and indefinitely without gastric irritation, insuring maximum
efficiency.”
“Reports show surprisingly good results, even where the sodium salt
fails.”
As there is no evidence to show that strontium salicylate, calcium
salicylate or a mixture of the two salts has any advantage over
sodium salicylate, these claims cannot be accepted. The name and the
statement of composition are objectionable in that they do not reveal
the identity of the drugs in “Calcylates” and in suggesting that this
preparation possesses radical advantages over salicylates in other
forms.
The Drug Products Company was told that the facts just mentioned
rendered “Pulvoids Calcylates” ineligible for New and Nonofficial
Remedies. The company in its reply objected to the Council’s
conclusions, and in support of its position submitted testimonials from
a number of physicians. The reply of the company embodied no facts or
arguments which had not been considered by the Council’s referee, and
the testimonials from physicians contained no evidence to show that the
combination has any real advantage over sodium salicylate.
The Council therefore declared “Pulvoids Calcylates” ineligible for
New and Nonofficial Remedies for the following reasons: Unwarranted
therapeutic claims are made for the mixture (Rule 6); the name does not
describe the composition (Rule 8), and the mixture is an unessential
modification of an established remedy (sodium salicylate) (Rule
10).--(_From The Journal A. M. A., Sept. 9, 1916._)
SULFURYL MONAL
Report of the Council on Pharmacy and Chemistry
Sulfuryl Monal is said to be manufactured by Monal Frères,
manufacturing chemists of Nancy, France. It is sold in the United
States by George J. Wallau, Inc., New York City. According to the label:
{Contains: Sulfuryl (combined polysulphurets)
{ = 0.35 centigr.”
“Each Pastille {
{Liberates: Nascent sulphurretted Hydrogen
{ = 2 cub. cent.”
The Chemical Laboratory of the American Medical Association was
requested to check the amount of available hydrogen sulphid. An
original bottle of Sulfuryl Monal was used; this contained tablets
having the taste of licorice extract and an odor of hydrogen sulphid.
The tablets were found to liberate about 6 c.c. hydrogen sulphid to
each tablet.
Among the claims made for the preparation are:
“Dissolved by the saliva, Sulfuryl Monal reaches the stomach
where, under the influence of the gastric juice, it generates
nascent sulphuretted hydrogen. Professor Albert Robin’s remarkable
researches have proven that it is in the nascent state that drugs
produce the greatest effect with the smallest dose.... Being thus
eliminated by the entire respiratory tract: the lungs, bronchi and
the throat, the sulphurretted hydrogen passes from the interior to
the exterior, that is to say, goes right through these organs which
are, as a consequence, thoroughly cleansed, antisepticized and
freed of the pathogenic micro-organisms.... Then, again, part of
the sulphuretted hydrogen, liberated in the stomach, is eliminated
by the mouth and acts as an antiseptic and disinfectant of the
mucous membranes of the throat and mouth. Hence Sulfuryl Monal is a
perfect protective agent against contagious diseases.... Numerous
clinical tests have demonstrated its real efficacy in diseases of
the throat and of the respiratory tract: laryngitis, pharyngitis,
hoarseness, granulations, tonsillitis, colds, bronchitis, pulmonary
catarrh, asthma, emphysema, grippe, whooping cough, simple
and infectious pneumonia, and in the first stage of pulmonary
tuberculosis.”
The sulphids are practically ignored in modern textbooks. There is a
rather extensive clinical literature on the subject, particularly in
connection with sulphur waters; this, however, offers no good evidence
for the therapeutic value of sulphids. Probably the tradition in their
favor is largely due to the old popular idea that a disagreeable taste
or odor is a mark of a good remedy.[95]
[95] Liquid Sulphur--Sulphume, J. A. M. A., Dec. 2, 1911, p. 1853.
When hydrogen sulphid is introduced into the body, the small amounts
that appear in the expired air are insufficient for quantitative
demonstration and it is highly improbable that the amount thus excreted
has any germicidal action, or that enough is excreted in the lungs to
cause irritation and a reaction. The claim that Sulfuryl Monal is “a
perfect protective agent against contagious diseases” is unwarranted;
the recommendation for its use in “simple and infectious pneumonia, and
in the first stage of pulmonary tuberculosis” is dangerous and vicious.
The Council declared Sulfuryl Monal ineligible for New and Nonofficial
Remedies and authorized publication of this report.
[Editorial Note..--With one exception, this product does not appear to
be advertised in medical journals. We find, however, in the gallery
of nostrums that grace the advertising pages of the _International
Journal of Surgery_, that Sulfuryl Monal has its place. According to an
advertisement that has been running some months in this publication,
“affections of the throat and respiratory organs respond promptly” to
Sulfuryl Monal whose “effects are rapid and certain” even in “incipient
tuberculosis.” This preposterous pronouncement is no worse than many
others appearing in the same journal, but it is bad enough to indicate
how uncritical must be the physicians who support--by subscription
or contribution--publications that are still debasing scientific
medicine.]--(_From The Journal A. M A., Sept. 16, 1916._)
MARK WHITE GOITER SERUM AND MARK WHITE IODINIZED OIL
Report of the Council on Pharmacy and Chemistry
The “Mark White Goiter Serum Laboratories” of Chicago asked the Council
to consider its products “Mark White Goiter Serum” and “Mark White
Iodinized Oil.” The “serum” was claimed to be an “antibody blood serum
from a goat with thyroidosis” while the “Iodinized Oil” was said to
contain “about 4 grains of iodin” to “each c.c.” The therapeutic
indications for the treatment were given as:
“Simple or Exophthalmic Goiter, Hyperthyroidism-dosis, Thyrosis,
Thyroidosis, Thyrotoxicosis, Dementia.”
An ampule (2 c.c.) of the “serum” is to be injected into the thyroid
to be followed one week later by an ampule (2 c.c.) of the “Iodinized
Oil.” Repetition of this “treatment” once or twice a month is advised.
The Council asked for more specific information as to the composition
of the remedies, particularly as to the preparation and nature of the
serum; it also asked for evidence of the therapeutic value of the
preparations. In reply, Mark White wrote:
“All that I can say regarding the serum is that it is made from the
blood of goats with thyroid affection, and it has been found that
the serum from these goats has antibodies which control, or has
curative effect upon thyroid affections when injected into thyroid
glands of either humans or animals. As to the iodinised oil, it
is only an adjunct or side treatment which is not always used or
indicated, and will only be furnished to the physician for use in
case in his judgment his patient needs it. We shall also advise the
use of quinin ... when indicated....”
The Council was referred for further information to a paper by Rachel
Watkins, M.D., published in the _Illinois Medical Journal_. It is to
be noted, incidentally, that the letterheads used by White in his
correspondence bore in one corner the notation “Rachel Watkins, M.D.,
Practice Limited to Goiter and Other Disorders of the Thyroid Glands,”
and in the other, “Mark White, Goiter Research.”
The information regarding the composition of this goiter treatment, as
furnished in Dr. Watkins’ paper, was to this effect:
“The medical treatment consists of the administration of a blood
serum derived from a thyrodized goat. Formula: Iodine 0.16 grams
[according to a correction by Mark White, this should read 0.26
gm.], oil 0.25 c.c., serum q. s. 1 c.c.”
This description of the treatment differs from that furnished to the
Council by Mark White in that here the iodin and oil appear to be
combined with the serum. Dr. Watkins’ “formula” implies that the iodin
is a routine medication, thus contradicting White’s statement, which,
in turn, is at variance with the statements made in submitting the
treatment.
[Illustration: Photographic reproductions (greatly reduced) of some of
the letterheads used by the Mark White concern during the past five
years.]
The Council does not accept any biologic product until its sale in
interstate commerce has been authorized by the secretary of the
treasury in accordance with the federal law regulating the sale of
viruses, serums, toxins and analogous products. The sale of the Mark
White Goiter Serum has not been so authorized; consequently even if the
preparation complied with other rules of the Council it could not be
accepted.
In addition, however, this treatment conflicts with other Council
rules. The statements regarding its composition are indefinite
and contradictory (Rule 1); the evidence presented to support the
therapeutic claims is insufficient in itself and does not appear to
have been checked by any disinterested authority (Rule 6). Moreover,
the recognized variation in the morphology and pathology of the types
of goiter render it impracticable to treat cases of goiter by any
routine procedure.
The foregoing report was submitted to the Mark White Goiter Serum
Laboratory. In reply, a letter signed “Mark White, V.M.D.,” was
received, which read, in part:
“... we hope at some future time to be able to give you more
detailed information, but as you possibly appreciate that we
have experienced for some time a demand on the part of many
physicians that we furnish to them our therapy, which necessitates
us furnishing it before all the detailed work has yet been
accomplished, and I trust that you will be so kind as to bear
patiently with us until we are better in a position to make a
complete scientific application and report to you.”
White wrote further:
“The serum and iodized oil may be mixed for immediate use, but
could not be put up only separate for the use of the profession and
the therapy furnished Dr. Watkins she mixed as used.”
This statement throws no light on the discrepancies in the statements
with regard to the place of the iodinized oil in the treatment, namely:
(_a_) the original statement that the oil was to be given a week after
the serum; (_b_) White’s statement (quoted earlier in this report) that
the oil “is only an adjunct or side treatment” and “is not always used
or indicated”; (_c_) the statement in Dr. Watkins’ paper that the oil
and the serum are given in combination.
The Council declared the Mark White Goiter Serum and Mark White
Iodinized Oil ineligible for New and Nonofficial Remedies and
authorized publication of this report.
Editorial Note on the Mark White “Serum”
As some of our readers will remember, on April 26, 1913, The Journal
called attention to the Mark White preparation which at that time was
being exploited from Denver. The Propaganda Department has in its files
a number of letters sent out from the Mark White concern at various
times. One mailed in May, 1911, on the embossed stationery of “The Mark
White Goiter Institute,” Exchange Building, Denver, was evidently a
general letter sent to physicians, calling their attention to “the most
important medical discovery of the age.” “Dr. Mark White, a graduate
of the University of Pennsylvania,” said the letter, had discovered “a
simple and harmless remedy” that would cure goiter. “Because of the
desire to preserve the secrecy of this remedy it is given only at the
office here.” It was then suggested that the doctor might send those
of his patients who were suffering from thyroidism to the “Mark White
Goitre Institute.” If he would do so he would be “given a commission
of $10, in cases of the $50 fee with the additional $5 for each $50
increase.” It closed with some casuistic arguments, presumably for the
purpose of overcoming the physician’s scruples, summing up the matter
with the statement:
“No right thinking man will allow a narrow and self-seeking system
of ethics to stand between him and his duty to the sick and
suffering.”
About 1912 the name of the concern seems to have been changed, for we
have in our files a letter addressed to a layman on the stationery of
the “Mark White Goitre Treatment Company.” According to this letterhead
the product this concern had for sale was “Goitreine” discovered by
Mark White, “President and General Manager.” Mr. White’s letter to the
sufferer from goiter assured him that if he would take “Goitreine”
he might “be practically sure of an immediate and permanent cure.”
“Goitreine,” according to White, “has absolutely and permanently cured
90 per cent.” of all cases of goiter in which it has been used--“and
the other ten showed remarkable improvement.” It was efficacious for
all forms of goiter and “cannot possibly harm.”
The person who received this assurance might have had his confidence in
it shaken had he seen a copy of the Denver _News_ for May 23, 1911, in
which was reported a case of collapse and death in a woman following
an injection given in White’s office. The paper stated that the death
certificate was signed by one W. A. Gray and gave “fatty degeneration
of the heart and goiter” as the cause of death. Gray, it seems, was the
licensed physician employed by Mark White to administer “Goitreine”--if
that is what White happened to be calling his product at that time.
For here it may be stated, parenthetically, that Mark White is not a
physician; he is a veterinarian.
In February, 1913, Mark White sent a circular letter to a number of
medical publications with the request that it be printed in full in
the next issue, “to cover one full page of space.” The letter White
wanted printed was addressed to doctors offering to “enter into a
copartnership agreement” with such physicians who would be willing to
treat “patients with goiter affections on a 50 per cent. commission
basis.”
“You would be expected to make a cash charge to the patient for the
treatment, remitting on the same day our 50 per cent. to us, when
ordering the treatment, giving the treatment in no cases for less
than $50.00.”
About the same time that Mark White made this “fifty-fifty” offer,
he sent in an advertisement to be published in the classified column
of The Journal. At that time he was told his advertisement was not
acceptable; we now reprint it, however, free of charge. Here it is:
“WANTED--ONE OR MORE PHYSICIANS
in each vicinity to administer and represent our new medical
treatment for GOITER. Good margin of profit. Write for copy of
contract. The Mark White Goitre Treatment Co., Denver, Colo.”
In 1914, White moved to Chicago. At least the card which we reproduce
so indicates. At that time, as will be seen, “Dr. Mark White” was
“personally associated” with Peter S. Clark, M.D. According to the
same card Dr. F. D. Paul of Rock Island, Ill., seems to have been his
“associate” for that particular locality. In this connection, it is
worth noting that a Rock Island paper, in one of its issues during
July, 1913, devoted a good deal of space to “Dr. Mark White” who
was at that time in Rock Island “directing Dr. Frank D. Paul in the
administering of the treatment.” There was nothing to indicate that
this notice was an advertisement or that the editorial appearing in the
same issue puffing White’s “important cure,” was paid for.
[Illustration: When exploited from Denver the Mark White “goiter cure”
was advertised in the daily papers. Here is a photographic reproduction
(reduced) of an advertisement that appeared in the Denver _Post_, Sept.
1, 1912.]
Dr. W. A. Gray, who has already been mentioned as White’s associate
in Denver, seems to have been doing business in Illinois some time in
1913 and a Princeton (Ill.) paper had some uncomplimentary things to
say about him. Finally in July, 1913, this item appeared in a Princeton
paper.
“Dr. W. A. Gray, the goiter specialist who operated last winter
at Princeton and Walnut until he became embroiled with Dr. Mark
White, a Denver veterinary and originator of the cure, over a
division of the spoils, has opened a goiter institute in Chicago
under his own name. Advertisements of the Dr. Gray Goiter Institute
appeared Sunday morning in the Chicago _Examiner_ and other morning
papers. Dr. Gray and Mark White broke off their relations after
their disagreement at Walnut, and Dr. Gray slightly changed the
ingredients of the goiter cure and started off on his own hook.”
One of Gray’s advertisements in Chicago newspapers made the claim that
“Dr. Gray’s New Medical Treatment removes the cause of goiter in seven
days.”
[Illustration: Photographic reproduction (reduced) of the
“professional” card used by “Dr. Mark White” after he came to Chicago.]
The Tulsa (Okla.) associate of “Dr.” White seems to have been Dr.
J. H. Morgan and the Tulsa papers of June, 1914, tell of “Dr.” White’s
visit to that city “for the purpose of instructing Dr. J. H. Morgan in
the technique of his new medical treatment for nervous disorders and
goiter.” Some months later--in December, 1915--the following little
item appeared in a Tulsa paper:
“Dr. Mark White was found guilty in the county court yesterday of
practicing medicine without a license and was fined $50. Doctor
White is a goiter specialist.”
In September, 1915, Mr. Thomas S. Hogan, the efficient counsel for the
Illinois State Board of Health, instituted action against Mark White
for practicing medicine without a license. The case was tried Oct. 15,
1915, and the jury, after being out four hours, returned a verdict
of “not guilty.” Attorney Hogan attributes the failure to obtain a
conviction to the testimony of Dr. Rachel Watkins, who said she had a
partnership arrangement with White in carrying on the medical business.
It was about this time that Mark White seems to have issued some new
letterheads. These bore in their upper left hand corner the device
“Rachel Watkins, M. D., Practice Limited to Goiter and Other Disorders
of the Thyroid Glands,” while the upper right hand corner read “Mark
White, Goiter Research.”
On Dec. 9, 1915, Rachel Watkins, M. D., of Chicago, read a paper
entitled “A Serum Treatment for Physiologically Defective Thyroids,
With Clinical Reports” before the Stock Yards Branch of the Chicago
Medical Society. The “serum treatment” discussed was Mark White’s
“Goitreine” which, in the course of its checkered career, had lost its
original name by the wayside. This paper appeared in the December,
1915, issue of the _Illinois Medical Journal_.
Probably emboldened by the ease with which a component part of the
American Medical Association “fell for” a paper exploiting a “goiter
cure,” Dr. Watkins requested that she be permitted to read a paper on
the same subject before the Section on Pharmacology and Therapeutics at
the Detroit meeting of the American Medical Association last June. The
request was refused. Dr. Watkins is apparently no longer connected with
White and in fact has protested against the use of her name by White in
connection with his “goiter cure.”
[After the above was in type and ready for the pages of The Journal,
attention was called to the _Official Bulletin of the Chicago Medical
Society_ of Sept. 16, 1916. This _Bulletin_ contained a full page
advertisement of the Mark White “goiter cure.” The advertiser referred
to the preparation as having been “announced to the Chicago Medical
Society” and declared it to be “an ethical therapeutic agent.”
Mark White was described as “a medical research student” but no
hint was given that he is a veterinarian. After again emphasizing
that “this therapy is ethically proven” physicians were invited
to “visit our goats when convenient” and the advertisement closed
with the modest claim that “this thyroid therapy has equal curative
therapeutic value in these cases as quinin in malaria.” And this sort
of pseudo-scientific claptrap is presented to a presumably learned
profession through its own official Bulletin--but what’s the use of
commenting!]--(_From The Journal A. M. A., Sept. 23, 1916._)
KORA-KONIA
Report of the Council on Pharmacy and Chemistry
Kora-Konia is a “dusting powder” which at present is advertised to the
medical profession through medical journals, circulars, post cards and
sample packages. It is put out by the “House of Mennen,” which sells
various toilet preparations such as talcum powder, shaving soap, etc.
On the trade package is the statement:
“Indicated in the treatment of Acne, Dermatitis, Eczema Intertrigo;
in obstinate cases of chafing, prickly heat, nettle rash, chicken
pox, measles, scarlatina and irritations of the skin; as a soothing
absorbent and antiseptic dusting powder and as an umbilical
dressing.”
While a circular asserts that:
“Kora-konia is indicated in the treatment of acne, dermatitis,
eczema and eczematous conditions of the utmost severity,...
eruptive fevers,...”
What purports to be a physician’s testimonial reads:
“I used Kora-Konia in a new born case of inherited syphilis and the
eruption soon cleared up.”
Germicidal powers are claimed for Kora Konia in a medical journal
advertisement. In view of the various claims made and the fact that it
is advertised to the medical profession, the Chemical Laboratory of the
American Medical Association was asked to analyze Kora-Konia. This was
done and the chemists reported as follows:
LABORATORY REPORT
Kora-Konia is a white powder, slightly greasy to the touch. Qualitative
tests showed the presence of boric acid, zinc, magnesium, a solid fatty
acid and material insoluble in hydrochloric acid containing magnesium
and aluminum. Starch was not found. Quantitative determinations gave
the following results:
Acid-insoluble material (talc) 48.3 per cent.
Magnesium (Mg++) soluble in dilute acid 1.2 per cent.
Zinc (Zn++) 4.5 per cent.
Stearic acid (impure) 39.2 per cent.
Boric acid 3.0 per cent.
Carbon dioxide (CO₂) 1.5 per cent.
From this analysis it is concluded that Kora-Konia has essentially the
following composition:
Zinc stearate U. S. P. 44 per cent.
Talc 48 per cent.
Magnesium carbonate U. S. P. 5.0 per cent.
Boric acid 3.0 per cent.
Essentially this dusting powder consists of the well-known substances
talc and zinc stearate in about equal proportions to which small
quantities of magnesium carbonate and boric acid have been added.
Inasmuch as the claim is made, by inference at least, that Kora-Konia
represents original investigation carried out “with the cooperation of
the medical profession” it should be stated that the preparation of
commercial zinc stearate was described and recommended as a dusting and
toilet powder nearly twenty-five years ago.[96]
[96] Proc. Am. Pharm. A. =40=:488, 1892.
There is nothing new or original in any one of these substances or in
the combination. The extravagant and unwarranted claims made for this
simple dusting powder are undoubtedly leading the public as well as
some thoughtless physicians, to place undeserved confidence in it.
In view of the small amount of boric acid present in the powder, its
antiseptic powers must be slight and its germicidal powers almost nil.
The Council declared Kora-Konia ineligible for New and Nonofficial
Remedies and authorized publication of this report.--(_From The Journal
A. M. A., Sept. 30, 1916._)
THE THERAPEUTIC VALUE OF THE GLYCEROPHOSPHATES
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Glycerophosphates are the salts of glycerophosphoric acid,
H₂[C₃H₅(OH)₂]PO₄. This acid is produced by the interaction of glycerin
and phosphoric acid. In general, only sodium glycerophosphate,
Na₂[C₃H₅(OH)₂]PO₄ + 5-1/2H₂O, and calcium glycerophosphate,
Ca[C₃H₅(OH)₂]PO₄ + H₂O, are used in medicine, though the
glycerophosphates of lithium, potassium, manganese, magnesium, iron,
quinin and strychnin are claimed as constituents of proprietary
preparations. At a time when certain disorders were assumed to be due
to a deficiency of phosphorus in the nerve structure in the body,
glycerophosphates were introduced as “nerve foods” and “tonics” on the
theory that they would be assimilated more readily than hypophosphites
or ordinary phosphates. What led to this assumption was the fact that
the lecithins, which form a part of the nerve structure, were known to
contain the glycerophosphate radical in the molecule. The belief that
inorganic phosphates cannot supply the body’s need of phosphorus is
implied or expressed in most of the “literature” devoted to proprietary
phosphorus preparations.
Thus, Schering and Glatz quote G. Meillière as saying that “the
organism is incapable of assimilating inorganic forms of phosphorus.”
Again, when exploiters of glycerophosphates admit that the body can
synthesize its phosphorus compounds from inorganic phosphates, they
attempt to counterbalance the admission by contending that the use
of organic compounds “spares” the system the necessity of making
such synthesis. This assumption rests on the theory that the organic
phosphorus compounds are absorbed and stored as such.
This theory is contradicted by evidence which has been presented[97]
that the organic phosphorus compounds are split up into inorganic
phosphates before absorption.
[97] McCollum and Hart, Grosser and Husler, Plimmer, and Bayliss and
Plimmer, quoted by Marshall (Note 2).
The Council requested E. K. Marshall, Jr., to review the evidence for
and against the therapeutic value of organic phosphorus compounds.
Marshall’s study[98] brings out the following points:
[98] Marshall, E. K.: The Therapeutic Value of Organic Phosphorus
Compounds, J. A. M. A., Feb. 13, 1915, p. 573.
1. In various tissues of the animal body, enzymes have been found which
hydrolyze complex organic phosphorus compounds so as to liberate the
phosphorus in the form of inorganic phosphates.
2. Metabolism studies of the phosphorus balance with diets containing
inorganic phosphorus compounds, as compared with diets containing
organically bound phosphorus, are somewhat conflicting in their
results. The balance of evidence, however, is in favor of the view that
there is no difference between organically combined phosphorus and
inorganic salts with respect to the phosphorus balance.
3. Experiments indicate that the organism thrives on and supplies its
phosphorus needs quite as well from inorganic phosphorus compounds as
from organically bound phosphorus.
Marshall concludes:
“We see that the evidence is very convincing of the view that the
animal organism can synthesize its complex organic phosphorus
constituents from inorganic phosphates, and that organic phosphorus is
of no more value as a food than inorganic.”
In view of this report, the Council deemed it advisable to take up the
consideration of certain glycerophosphate preparations on the market.
As the therapeutic claims are all similar, it is not necessary to quote
them extensively.
TONOLS (SCHERING’S GLYCEROPHOSPHATES)
Tonols (Schering and Glatz, New York) comprise iron, lime, lithium,
magnesium, manganese, potassium, quinin, sodium and strychnin “Tonols”
or glycerophosphates; also Duotonol Tablets, said to contain equal
parts of calcium and sodium glycerophosphates; Triotonol Tablets,
each said to contain “Sodium Tonol 2-1/2 grains, Lime-Tonol 2-1/2
grains, Strychnine-Tonol 1/60 grain”; Quartonol Tablets, said to
contain “Sodium and Lime-Tonols, each 2-1/4 grains, Quinine Tonol
1/2 grain, Strychnine-Tonol 1/200 grain”; Sextonol Tablets, said to
contain “Sodium and Lime-Tonols, each 2 grains, Iron-Tonol, 1/2 grain,
Manganese and Quinine-Tonols, each 1/4 grain, Strychnine-Tonol, 1/200
grain.”
The name “Tonols” is objectionable in that it is not only
nondescriptive of the composition, but also therapeutically (and
falsely) suggestive. The composition of the more elaborate Tonols is
particularly unscientific; there is no justification for combining
quinin, strychnin, iron, manganese, etc., in one formula.
PHOSPHORCIN COMPOUND
Phosphorcin Compound, called “The Elementary Phosphorus indicated in
all forms of Nervous Diseases” and the “Perfect Formula,” is said to
be manufactured by the Organic Products Company, Wetzlar an der Lahn,
Germany, and Greenwich, Conn. It is sold in the United States by Eimer
and Amend, New York, according to whom:
“Each two fluidrachms contain:
“Acidulated Bone Phosphor O. P. Co. 2 grains
“Calcium Glycerinophosphate, Merck & Co. 1-1/2 grains
“Magnesium Glycerinophosphate, Merck & Co. 1-1/2 grains
“Sodium Glycerinophosphate, Merck & Co. 2-1/2 grains
“Lactated Pepsin 2 grains
“Ignatia Extract 1/20 grain
“C. P. Glycerin (Special Process) O. P. Co. 50 per cent.
“Acidulated bone phosphor” presumably is acid phosphate of calcium.
This formula is an unscientific shotgun combination.
ROBINOL
Robinol, manufactured by John Wyeth and Brother, Philadelphia, is
called a “Universal Tonic.” It is said to be:
“A preparation of the glycerophosphates of lithium, calcium,
sodium, iron, manganese, quinine, with 1-16 gr. strychnine
glycerophosphate in each fluidounce.”
This is a semisecret preparation, since the quantities of most of the
ingredients are not given and the vehicle is not named. This complex
combination, too, is unwarranted.
PHOSPHOGLYCERATE OF LIME (CHAPOTEAUT)
This is said to be prepared by the Laboratories de Pharmacologie
Générale, Dr. Ph. Chapelle, Paris and New York. It is sold in this
country by E. Fougera and Co., Inc., New York. It is offered in several
forms, especially in that of wine, which is called the “Medicinal Wine
and Tonic Par Excellence.” The alcohol is no doubt the constituent
to which this preparation is indebted for such popularity as it has
attained, for it is much more freely advertised than the syrup,
capsules or granulated form. The usual claims are made with regard to
the efficacy of calcium glycerophosphate “during convalescence, in
cases of enfeebled vitality, and nervous affections associated with an
excessive elimination of phosphates.”
ELIXIR GLYCEROPHOSPHATES, NUX VOMICA AND DAMIANA
This is manufactured by Sharp and Dohme, Baltimore. The manufacturers’
statement of composition is:
“Each fluidounce represents Nux Vomica 8 grains, Damiana 64 grains,
combined with Glycerophosphates of Calcium and Sodium.”
“Alcohol 20 per cent.”
Sharp and Dohme call this mixture a “Reconstructive Nerve Stimulant,
Aphrodisiac,” and claim that:
“Phosphorus in elemental form has long been prescribed under the
title of Elixir Phosphorus, Nux Vomica and Damiana, but due to the
rapidity of chemical change occurring in preparations containing
this form of Phosphorus, much of the Physiologic action is lost.
The Glycerophosphates present Phosphorus in its most available
form--the form in which it exists in the brain and nervous system.
They powerfully stimulate the functions of nutrition and are
rapidly assimilated by the system.
“Nux Vomica is a general Nerve Tonic. Damiana exerts a stimulant
effect upon the sexual appetite and function.”
The claim that the glycerophosphates may be substituted for elementary
phosphorus is, at least, novel.
The elixir is an unscientific semisecret combination.
RECOMMENDATIONS
All of the preparations mentioned violate Rule 6 (unwarranted
therapeutic claims). In addition, Robinol and Elixir Glycerophosphates,
Nux Vomica and Damiana violate Rule 1 (secrecy of composition) in
that not all the quantities of the ingredients are declared; Tonols,
Phosphorcin Compound and Robinol violate Rule 8 (objectionable names).
It is recommended that the Council endorse Marshall’s findings[98] and
declare that Tonols (Schering and Glatz), Phosphorcin Compound (Eimer
and Amend), Robinol (John Wyeth and Brother), Phosphoglycerate of
Lime Chapoteaut (E. Fougera and Co.), and Elixir Glycerophosphates,
Nux Vomica and Damiana (Sharp and Dohme) are ineligible for New and
Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 30, 1916._)
HYDRAS
Report of the Council on Pharmacy and Chemistry
Hydras, sold by John Wyeth and Brother, Philadelphia, is one of the
many proprietary, so-called “uterine tonics.” It is said to contain
“Cramp Bark, Helonias Root, Hydrastis, Scutellaria, Dogwood and
Aromatics,” but as the amounts of the several ingredients are not
given the statement regarding its composition is valueless. The label
declares the presence of 24 per cent. alcohol.
The name “Hydras,” taken in connection with the statement of
composition, would suggest that hydrastis (golden-seal) is an important
constituent. The report of the Chemical Laboratory of the American
Medical Association, however, indicates that hydrastis is present in
unimportant amounts:
“The hydrastin content of Hydras was determined by extraction with
immiscible solvents (_Pharm. Review_, May, 1908, p. 132). Twenty-five
c.c. was found to yield an alkaloid residue of 0.0160 gm. The
preparation contains, therefore, not more than 0.064 gm. ‘hydrastin’
per 100 c.c. Inasmuch as hydrastis is required to contain about 2.5
per cent. ‘hydrastin,’ hydras contains an equivalent of not more than
2.56 gm. hydrastis (golden seal) in 100 c.c. and the stated dose of
Hydras--one dessertspoonful (8 c.c.)--represents not more than 0.2 gm.
or 1/10 of the U. S. P. average dose of hydrastis.”
The label of a recently purchased bottle of Hydras bears the following
recommendations for its use:
“Indicated in treatment of Dysmenorrhea, Menorrhagia Anti-Abortive,
with anodyne and tonic properties.”
“For dysmenorrhea, suppressed menses, etc., a dessertspoonful three
times daily, before or after meals.”
“To relieve pain due to uterine disorders, a dessertspoonful every
three hours, or increased to a tablespoonful, at the discretion of
the attending physician.”
A circular wrapped around the bottle declares that Hydras is:
“A valuable preparation to the physician in the treatment of
dysmenorrhea, colic, cramps, spasm, palpitation incident to
pregnancy, and the various pains resulting from diseases of the
female sexual organs.”
It is further claimed that:
“In the dysmenorrhea of young girls due to some mechanical
difficulty, as anteflexion or of a congestive character, of
suppressed menses from exposure to cold and other causes of
a similar character, Hydras will prove efficient and can be
administered freely without danger.”
The value of hydrastis in the treatment of the diseases and conditions
mentioned is problematical at best, and the small amount present in
Hydras is wholly useless. As for the other constituents, cramp bark
(_Viburnum opulus_), helonias (false unicorn--_Chamælirium luteum_
or _Helonias dioica_) and scutellaria (skullcap--_Scutellaria
lateriflora_) are drugs which are practically ignored by most writers
on materia medica and therapeutics.[99] Dogwood (_Cornus florida_) is
a mildly astringent aromatic bitter for the use of which there is no
scientific evidence.[100]
[99] See reports of the Council, J. A. M. A., Jan. 9, 1915, p. 165;
Jan. 23, 1915, p. 359; Nov. 27, 1919, p. 1836; March 27, 1915, p. 1093.
[100] See Reports Council Pharm. and Chem., 1912, p. 36.
To sum up: Of the five ingredients of Hydras (aside from alcohol and
aromatics), one (hydrastis), which apparently gives the preparation its
name, is present in unimportant amounts; three (cramp bark, helonias
and scutellaria) are therapeutically unimportant; the fifth (dogwood)
has never been shown to have any specific action on the uterus. The
potent constituent, therefore, appears to be the alcohol.
But, even if every one of the several drugs said to be contained in
Hydras were possessed of distinct therapeutic properties, and if each
were present in known and therapeutically active amounts, still the
combination in fixed proportion would be irrational. No one could
foresee the joint effect of the five drugs in the several conditions
for which the mixture is advertised. Hydras is evidently meant to
appeal to the thoughtless and to be used at random; witness the
suggestion made in the advertising that
“Owing to its palatability, it is acceptable to patients with
impaired digestion, and will serve as a stomachic tonic, promoting
appetite and digestion.”
A useless alcoholic nostrum “administered freely” to women and girls
is as dangerous as the recommendation for such administration is
reprehensible.
This preparation is semisecret. The recommendations for its use in
specified diseases which appear on the label and in the advertising
accompanying the bottle are sure to lead to its ill-advised use by the
public. The claims made for its curative properties are exaggerated
and unwarranted. The name, in view of the small content of hydrastis,
is misleading. Finally, the combination of five drugs, even if
individually they were of therapeutic value, is irrational. Hydras,
consequently, is inadmissible to New and Nonofficial Remedies for
conflict with Rules 1, 4, 6, 8 and 10, and publication of this report
is authorized.
[Editorial Comment.--Products like “Hydras” are the bane of scientific
medicine. The physician who prescribes them could with just as much
reason prescribe any of the various alcoholic “patent medicines” of
the “women’s tonic” type. In fact, his patients would be running less
risk of contracting the alcohol habit if he prescribed the “patent
medicines,” as these nostrums usually have less alcohol than is
contained in their “ethical” prototypes--and alcohol is the only really
important drug in practically all of them. Whatever one may think of
reputable pharmaceutical houses who put out products of the “Hydras”
type, the fault really lies with the profession which tolerates such
therapeutic monstrosities.]--(_From The Journal A. M. A., Oct. 7,
1916._)
BROMIN-IODIN COMPOUND
Report of the Council on Pharmacy and Chemistry
“Bromin-Iodin Compound,” according to the Bromin-Iodin Chemical
Company, San Diego, Calif., has the following “formula”:
Iodin Gr. 1
Bromin Gr. 1/4
Phosphorus Gr. 1/100
Thymol Gr. 2/3
Menthol Gr. 2/3
Sterilized Oil Gr. 1
The only statement regarding its method of preparation is the line
“Solution in Cod Liver Oil, Norwegian.” According to the promoters,
“Bromin-Iodin” is:
“A Powerful Anti-Tubercular Agent for Hypodermic Use in Pulmonary
and Laryngeal Tuberculosis. Useful in other forms of Tubercular
Diseases, and in Non-Tubercular Pulmonary Diseases of a Sub-Acute
or Chronic Nature.”
The “formula,” in the form in which the manufacturers publish it, is
either impossible or meaningless, according to the interpretation that
may be given. It is impossible if it is intended to indicate the actual
composition of the product because that would mean that the oil is
alleged to contain free or uncombined iodin, bromin and phosphorus.
Both on theoretical grounds and also in the light of the findings of
the Chemical Laboratory of the American Medical Association, it is
not possible that all these constituents can be present in the free
state. The formula is meaningless if it is intended to convey the idea,
merely, that iodin, bromin, phosphorus, thymol, menthol and sterilized
oil are combined to form “Bromin-Iodin.” In the absence of any details
of the method of manufacture, it is futile to attempt to pass judgment
on the actual composition of the preparation.
The use of an almost identical product (said, however, to contain
only 1/2 grain iodin to each fluidram) was described in 1908 by Dr.
Ingraham of Binghamton, N. Y., in “Five Years Successful Experience
with a Special Mode of Treating Pulmonary Tuberculosis.” In 1910 The
Journal[1] characterized the preparation as “one of the innumerable
‘treatments’ for pulmonary tuberculosis that have arisen, had their
day and, more or less gracefully, retired.” If the preparation had
value for the purpose for which it is recommended, its use during these
twelve years should have secured its general recognition. There is no
satisfactory evidence of its therapeutic efficacy. The Council refused
recognition to Bromin-Iodin Comp. and, after submitting this report to
the Bromin-Iodin Chemical Company, authorized its publication.--(_From
The Journal A. M. A., Dec. 23, 1916._)
AMMONIUM HYPOPHOSPHITE OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Ammonium hypophosphite was admitted to New and Nonofficial Remedies
in 1908 as a preliminary step in the consideration of a preparation
containing it--“Gardner’s Syrup of Ammonium Hypophosphite”--because
the Council standardizes unofficial products before considering
preparations or mixtures of these.
The therapeutic use of hypophosphites being irrational (see, “The
Hypophosphite Fallacy,” Report of the Council on Pharmacy and
Chemistry, The Journal, Sept. 2, 1916, p. 760), the salt, ammonium
hypophosphite, deserves continued recognition only on condition that
this salt of ammonium is superior to other salts from which may be
obtained the effect of the ammonium radical. It has been claimed that
ammonium hypophosphite has a less objectionable taste than other
ammonium salts used for similar purposes. This claim would merit
serious consideration if in addition to being less objectionable to
the taste, the effects of ammonium hypophosphite were equal to or more
desirable than the official ammonium salts. There is no evidence that
this condition is met by the hypophosphite salt.
Ammonium hypophosphite has long been known, yet it is not official
in the Austrian, Belgian, British, French, German, Hungarian,
Italian, Swedish, Swiss or United States Pharmacopeias. Neither is it
mentioned in the leading textbooks on materia medica, pharmacology or
therapeutics. In short it appears to be an instance of an obscure and
superfluous salt selected for proprietary exploitation.
Since the continued recognition of ammonium hypophosphite would tend to
perpetuate the hypophosphite fallacy, and because there is no evidence
supporting its advantage as a means of securing the effect of ammonium
salts the Council directed its omission from New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1916,
p. 51._)
ALPHOZONE OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following advertisement appeared in the _New Idea_ (September,
1916), a house organ of Frederick Stearns & Co., the proprietors of
Alphozone:
[Illustration]
In the light of our present knowledge the claim that Alphozone is a
preventive of infantile paralysis is without warrant and the advice
that the public depend on it for this purpose is reprehensible and
dangerous. Therefore, the Council directed that Alphozone be omitted
from New and Nonofficial Remedies.--(_From Reports of Council on
Pharmacy and Chemistry, 1916, p. 50._)
CALCIUM GLYCEROPHOSPHATE AND SODIUM GLYCEROPHOSPHATE
OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Calcium glycerophosphate and sodium glycerophosphate were accepted
for New and Nonofficial Remedies chiefly in order that these products
might be standardized. These mixtures now being defined in the new
edition of the U. S. Pharmacopeia, this reason for including them
in N. N. R. no longer exists. The report of Marshall (The Journal,
Feb. 13, 1915, p. 573) which has the endorsement of the Council (The
Journal, Sept. 30, 1916, p. 1033) shows that organic phosphorus
compounds are split up into inorganic phosphates before absorption,
that the animal organism can synthesize its complex organic phosphorus
constituents from inorganic phosphates and consequently that the
glycerophosphates, so far as their phosphorus value is concerned, are
not superior to other phosphates. In fact, sodium and phosphate are
more effectively administered as neutral or acid phosphate. It is
evident that sodium glycerophosphate is a superfluous pharmaceutical
preparation, particularly when the difficulty of obtaining a pure
product and its high price is considered. So far as its calcium value
is concerned, calcium glycerophosphate has no advantages over such
calcium salts as the carbonate, phosphate, lactate, or chlorid. In view
of the foregoing, the Council directed that sodium glycerophosphate
and calcium glycerophosphate be omitted from New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry_, 1916,
p. 52.)
GARDNER’S SYRUP OF AMMONIUM HYPOPHOSPHITE OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
In recognition of the considerable revision of the therapeutic claims
made by the manufacturer, Gardner’s Syrup of Ammonium Hypophosphite
was retained in New and Nonofficial Remedies, 1916, and the proprietor
advised of this provisional retention.
In the most recent advertising for this ammonium hypophosphite syrup
the claim is made:
“Besides being an active expectorant Syrup of Ammonium
Hypophosphite (Gardner) is useful as an alterative and resolvent
and by virtue of its phosphorus element, which is in the form of a
hypophosphite, PH₂O₂, has a tonic value.”
As detailed in the report of the Council “The Hypophosphite Fallacy”
(The Journal, A. M. A., Sept. 2, 1916, p. 760) careful studies show
that the hypophosphites are devoid of the “alterative” and “tonic”
actions claimed by the manufacturer of Gardner’s Syrup of Ammonium
Hypophosphite. Accordingly the Council voted to omit Gardner’s Syrup of
Ammonium Hypophosphite from New and Nonofficial Remedies and authorized
publication of this report.--(_From Reports of Council on Pharmacy and
Chemistry, 1916, p. 55._)
GLUTEN PRODUCTS MADE BY THE KELLOGG FOOD COMPANY
Report of the Council on Pharmacy and Chemistry
For over two years the Council has had under consideration certain
products offered for the use of diabetics by the Kellogg Food Company
of Battle Creek, Mich. These are:
Pure Gluten Biscuit.
Pure Gluten Meal.
40 per cent. Gluten Biscuit.
40 per cent. Gluten Flour.
40 per cent. Gluten Meal.
20 per cent. Gluten Meal.
The Council found these products ineligible for New and Nonofficial
Remedies because the statements of composition (particularly of starch
content) were insufficient and because the exploitation of the products
to the laity was objectionable. June 21, 1915, the company promised to
place a statement of the starch content on the package of each gluten
product, to place on the gluten flour sacks a caution that diabetics
use the flour only on the advice of their physicians, and to revise its
advertising in accordance with the suggestions of the Council. Nothing
further having been heard from the company, in April, 1916, specimens
of the product were obtained, through a layman, direct from the
Kellogg Food Company. These specimens, together with the advertising
matter received at the same time, and also a letter of advice from the
company to another layman, were sent to the Council’s referee, whose
report follows. As will be seen, the referee finds that the amounts
of carbohydrates contained in Pure Gluten Flour, 40 per cent. Gluten
Flour and Pure Gluten Meal are greater than the amounts claimed in
the company’s published analyses; that in the two first mentioned the
amounts of protein are less than the amounts claimed; that exaggerated
claims are made on all the labels and in the advertising literature,
and that the company prescribes directly to the patient.
The following report was sent to the Kellogg Food Company for
consideration. In reply the firm stated that a revision of its
advertising was under consideration but would make no statement
as to how soon this revision would be carried into effect. As the
consideration had already consumed two years, the Council decided to
give the profession the facts and authorized publication of the report.
At the same time the Kellogg Food Company was advised that its products
would be considered further whenever any submitted evidence warranted
this.
W. A. Puckner, Secretary.
Referee’s Report
I submit herewith my report on certain foods offered by the Kellogg
Food Company for the use of diabetics. I shall discuss these products
from the standpoint of the claims made on the label, from the
standpoint of the company toward nonmedical treatment as revealed in a
letter to a layman, and lastly, on the basis of the claims made for the
foods in the company’s literature.
CLAIMS MADE ON THE LABEL
PURE GLUTEN BISCUIT
Referee Company
Water 8.30 5-10
Ash 2.04 1-2
Protein (N × 5.7) 73.87 75-80
Fiber 0.12 2.4-3
Carbohydrates 14.84 0-5
Fat 0.81 0.25-0.70
Starch 4.02 0-5
The sample analyzed does not contain the amount of protein claimed
for it. It also contains more starch than one might suspect from the
company’s analysis. A more conservative claim would be “starch less
than 5 per cent.” The company makes the error of using the terms
“starch” and “carbohydrates” as synonymous. If the maximum figures of
the company’s analysis are used, the carbohydrates would amount to
5 per cent., whereas I find 14.84 per cent. The claim on the label
“Guaranteed to contain less than 5 per cent. of carbohydrates” is
incorrect. The next claim, “Each ounce of this gluten contains 23 grams
of protein and represents 95 calories” is approximately correct, as my
analysis shows 20.9 grams of protein and 103 calories.
The following remarks under “Vegetable Proteins” are in my judgment
exaggerated:
“Leading authorities are now agreed that meat, fish, eggs and
other animal proteins are greatly inferior to vegetable proteins
in diabetes, often increasing the sugar output and the dangerous
acidosis which leads to diabetic coma.... After many years of
experimentation, we have succeeded in perfecting a process whereby
the carbohydrates are excluded.”
In this connection, von Noorden, whom the company constantly quotes,
says:
“In the slighter forms (of diabetes), the influence of meat
albumins is not great and it is difficult to demonstrate the
reaction of the patient to different forms of albumin. It may be
necessary to add more albumin than the patient can actually take
before glycosuria indication is reacted.... Once a medium amount of
albumin is exceeded, say 70 to 80 grams, the glycosuria increases,
no matter what the type of albumin is.”
My analysis also shows that the carbohydrates are not excluded from
this food as claimed above.
40 PER CENT. GLUTEN BISCUIT
Referee
Water 8.50
Ash 1.48
Protein (N × 5.7) 41.15
Fiber 0.08
Carbohydrates 47.81
Fat 0.98
Starch 36.98
No analysis is supplied by the company, but this may be called properly
a “40 per cent. Gluten Biscuit.” The company claims, however, that this
is “Best for Diabetics,” which is not true.
Here, as in the case of “40 per cent. Gluten Flour,” the company’s
label attributes to “Dr. Wm. Osler in ‘Practice of Medicine,’” the
following quotation: “Of Gluten Foods, many are very unpalatable,
others are frauds. A Good Gluten Flour is made by the Battle Creek
Sanatarium Co., Mich.” I have no way of knowing to which gluten flour
of the company Dr. Osler had reference. The “Pure Gluten Meal” might be
called properly a “good gluten flour,” but this “40 per cent. Gluten
Flour” is no better, and no worse, than the average gluten flour on the
market. The quotation from Osler gives an entirely false impression.
40 PER CENT. GLUTEN FLOUR
Referee Company
Water 8.62 5-10
Ash 0.89 0.5-1
Protein (N × 5.7) 33.63 40-45
Fiber 0.08 1-3
Carbohydrates 55.35 40-45
Fat 1.43 0.2-0.5
Starch 48.04 ...
My analysis shows 6.37 per cent. less protein than the company’s
minimum, and 10.35 more carbohydrates than their maximum. In past years
I have found the protein in this brand to range from 35.0 to 42.9 per
cent. (using the factor 5.7). It is true that the manufacturer does
not state what protein factor is used in his reported analysis, but as
in four other brands 5.7 is used, it is fair to assume that the same
factor applies to this as well. At least such should be the case, as
otherwise the manufacturer’s analyses would be meaningless. Even using
the factor 6.25 this later sample contains only 36.88 per cent. of
protein.
The following statement, in my judgment, as applied to a food
containing over 48 per cent. of starch, does not hold water: “This
food is of special service in cases of Glycosuria and in the milder
forms of Diabetes.” With this brand as with “40 per cent. Gluten
Biscuit” the manufacturer again uses the misleading quotation from
Osler.
40 PER CENT. GLUTEN MEAL
Referee Company
Water 7.30 5-10
Ash 1.36 1-2
Protein (N × 5.7) 41.55 40-45
Fiber 0.10 1-2
Carbohydrates 48.58 40-45
Fat 1.11 0.2-0.5
Starch 36.59 40-45
The claimed analysis is justified by my findings. I must take
exception, however, to the following statement: “Prepared with great
care from a good grade of Spring Wheat, by our special process, which
preserves the natural food properties of the product.” The company
evidently tries to carry water on both shoulders, on the one hand
claiming a reduction in the starch content, while on the other claiming
the preservation of all “the natural food properties.”
20 PER CENT. GLUTEN MEAL
Referee Company
Water 7.65 5-10
Ash 1.22 1-2
Protein (N × 5.7) 24.68 20-30
Fiber 0.12 1-2
Carbohydrates 65.41 65-70
Fat 0.92 1-2
Starch 51.24 65-70
The company’s analysis is confirmed. As the company claims directly
that this is “Not A Diabetic Food,” any criticism of its use for
that purpose is disarmed. However, again exception must be taken to
the statement that “the natural food properties of the product” are
preserved.
PURE GLUTEN MEAL
Referee Company
Water 4.60 5-10
Ash 0.96 1-2
Protein (N × 5.7) 76.78 75-80
Fiber 0.08 1-3
Carbohydrates 16.77 0-5
Fat 0.81 0.25-0.70
Starch 6.77 0-5
The minimum claim as to protein is justified. Again the company
confuses carbohydrates and starch, and the food instead of containing
from 0 to 5 per cent. of “carbohydrates (starch)” actually contains
16.77 per cent. of carbohydrates, of which 6.77 per cent. is starch.
Once more the statement that “the natural food properties” are
preserved is untrue as applied to a wheat product deprived of most of
its starch.
In justice to the company, it should be noted that on the labels of
“Pure Gluten Biscuit” and “Pure Gluten Meal” appears the warning:
“Every person suffering from diabetes should be under the care of
an experienced physician,” and on the label of “40 per cent. Gluten
Meal,” “Persons suffering from diabetes should use this food only on
the advice of a physician.” On the other hand, the suggestion on the
label of “Pure Gluten Meal,” “Write for a copy of Diabetic Foods and
How to Use Them” is a more or less direct invitation to self-treatment.
Moreover, a letter dated May 9, 1916, apparently dictated for the
Kellogg Food Company by one Ruth French, in reply to an inquiry from a
layman, gives direct advice with no reference whatever to a physician.
CLAIMS MADE IN A LETTER TO A LAYMAN
In addition to this inconsistent attitude the letter makes certain
clear misstatements, as follows:
“40 per cent. Gluten Flour actually contains 40 per cent. of pure
Gluten, making it a perfectly safe article of diet in all but the
gravest cases of diabetes. From our Gluten Flour excellent bread, gems
and puffs are made that perfectly satisfy the craving for bread with no
harmful results.” This flour contains 33.63 per cent. of gluten, not 40
per cent.; it is not “a perfectly safe article of diet in all but the
gravest cases of diabetes,” for if one reads the literature correctly,
starch restriction is more necessary in mild than in severe cases of
diabetes. Furthermore, the bread, gems and puffs made from such a flour
do not “satisfy the craving for bread with no harmful results.”
In the next paragraph of the letter, undue emphasis is laid on the
“objectionable properties” of flesh foods, a statement only in accord
with the tenets of extreme vegetarians. I also doubt very much whether
the statement is true that “under a diet of our diabetic foods the
thirst to which diabetics are so often subject is usually very much
relieved.”
In the next paragraph the assertion is made that “The diet indicated
... is in keeping with the ideas of the highest medical authorities....
Meat is entirely excluded from the dietary.” My reading of the
literature does not show that the leading authorities take any such
position. Later on reference is made to von Noorden’s claim as to the
superiority of vegetable over animal proteins, which I have already
discussed under “Pure Gluten Biscuit.” (Certain detached sentences of
von Noorden might justify such a statement, but a reading of all he
says on the subject leads to a very different conclusion.)
CLAIMS MADE IN AN ADVERTISING BOOKLET
The whole booklet is written from the standpoint of an extreme
vegetarian, and therefore is often misleading in its conclusions.
Page 5. “The researches of Ogata and others have shown that cane sugar
is a less wholesome food than the natural sugars found in fruits and
produced in the body by the digestion of starch, that is, fruit sugars
and malt sugars.” In opposition to this I quote from von Noorden, their
own authority, “Die Zuckerkrankheit und ihre Behandlung,” Berlin, 1910,
page 270:
“That levulose, milk sugar and inulin are more useful than the other
carbohydrates is a common opinion, but the importance of their use in
practice does not correspond with the theory. In light cases the form
of carbohydrates makes little difference; in severe cases the advantage
from using levulose, milk sugar, etc., is only slightly greater than
from using bread and flour.... Only in certain cases does it appear
to me that the special form of carbohydrates possesses any particular
significance.”
On page 92 of the same work von Noorden tells us that of the
carbohydrates dextrose is the worst, with maltose almost as bad (in
spite of the fact that Kellogg exploits his “Meltose,” the “new
carbohydrate,” as of special value for diabetics). He also says that
levulose increases glycosuria only about half as much as dextrose,
when used occasionally, but with long use it is as bad as dextrose and
starch.
Page 5. The company refers to sugar as “possibly also causing
diabetes.” Sugar or any other carbohydrate may under diabetic
conditions cause an increase of glucose in the urine, but I do not
believe that any food or any diet can cause diabetes.
Page 7. “That the large use of meat and eggs is not only detrimental
but positively dangerous in many cases of diabetes is now a well known
and recognized fact.” The dietaries of well known authorities on
diabetes are not in harmony with this statement.
Page 13. “It has been discovered that the complete suppression
of carbohydrates from the dietary is not only unnecessary but is
highly detrimental and even dangerous.” “The complete suppression of
carbohydrates from the dietary” is the only means the physician has to
determine the diabetic’s carbohydrate tolerance. If carbohydrate-poor
foods are so “highly detrimental and even dangerous,” why does the
company exploit foods like “Pure Gluten Flour” and “Pure Gluten
Biscuit,” whose chief claim to excellence is their comparative freedom
from carbohydrates?
Page 17. “Cream is an emulsion, and, with the exception of egg yolk,
is the only form in which animal fat is found in an emulsified state.”
Milk, Nature’s most wonderful emulsion, is apparently overlooked.
Page 19. “... these foods ... will be found of great value ...
especially as substitutes for the breads and meats which are the most
objectionable features of the ordinary diet, and which should, as far
as possible, be interdicted in this class of cases.” This is simply
special pleading for the Kellogg vegetarian diet.
Page 19. “Our glutens ... are all thoroughly standardized, so that in
their use the physician and the patient know just the amount of starch
eaten.” This standardization is largely mythical. For instance, “Pure
Gluten Biscuit” claims 0 to 5 per cent. “carbohydrates (starch),”
whereas I find 14.84 per cent. carbohydrates with 4.02 per cent.
starch. “40 per cent. Gluten Flour” claims 40 per cent. gluten and
40 to 45 per cent. carbohydrates, whereas I find 33.63 and 55.35
per cent., respectively. “Pure Gluten Meal” claims 0 to 5 per cent.
“carbohydrates (starch)” whereas I find 16.77 per cent. carbohydrates
and 6.77 per cent. starch. I have a record of six analyses each of “40
per cent. Gluten Flour” and “40 per cent. Gluten Biscuit,” which show
the hollowness of this claim of “standardization.” The flour showed
33.6, 35.0, 42.9, 36.8, 35.6, and 40.9 per cent. of protein, with from
40.8 to 55.4 per cent. of carbohydrates; the biscuits 32.7, 33.2, 39.5,
43.3, 33.9, and 41.2 per cent. of protein, with from 41.1 to 54.0 per
cent. of carbohydrates. In fact, my experience shows that the Kellogg
products are more poorly “standardized” than most of the diabetic foods
on the market.
Page 20. “May be made to carry a large amount of fat in the form of
butter, a most desirable thing in the treatment of diabetes,” while on
page 16 the company claims that in an experiment of Minkowski on a dog,
butter “passed through the body without change, none being absorbed”;
these are certainly contradictory statements. The explanation is that
on the one page the company is exploiting its biscuits, and on the
other its nut preparations.
Page 20. Again the incorrect claim is made for “40 per cent. Gluten
Flour” that “we believe this to be the only standardized gluten flour
made.”
Page 21. The claim is made that flesh foods are “objectionable on
account of the large amounts of ptomains and toxins which they
contain.” I was not aware that fresh meats contained any ptomains
whatever. On the same page the claim is again made that by the use of
the Kellogg nut foods “diabetics lose their thirst,” a claim which I
think is more than doubtful.
Page 22. “Nuts are a whole food, containing all the elements required
for the perfect nutrition of the body.” A marked characteristic of
nuts is that they are not “a whole food,” as with the exception of
a few varieties, such as the chestnut, they are extremely poor in
carbohydrates, which fact gives them their value in the diabetic diet.
Page 23. “With the exception of the potato, the beet and the carrot,
vegetables contain little sugar or starch.” Corn, beans and peas are
all vegetables which are relatively high in carbohydrates, and for this
reason are specifically excluded from the diabetic’s dietary.
From the foregoing considerations I would recommend that the company’s
analyses of “40 per cent. Gluten Biscuit,” “40 per cent. Gluten Meal,”
and “20 per cent. Gluten Meal” be accepted as correct. Before the
Council can accept any of these products, the following steps should be
taken:
The company on all its labels should correct the impression that
“carbohydrates” and “starch” are synonymous terms.
The labels of all the preparations examined should be changed in
accordance with the criticisms given above.
In all cases in which analytic data are given, it would be preferable
to state only the minimum of protein and the maximum of carbohydrates.
The booklet, “Practical Suggestions About Diet in Diabetes,” should
be radically changed along the lines noted above.--(_From Reports of
Council on Pharmacy and Chemistry, 1916, p. 56._)
IODO-MANGAN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Iodo-Mangan, made by the Chemische Fabrik Helfenberg A. G., near
Dresden, Germany, and sold in the United States by the Reinschild
Chemical Company, New York, is a solution said to contain iron,
manganese and iodin in combination with peptone. It is claimed to
be a reconstructive tonic and blood-making adjuvant, with favorable
action in affections of the glandular system. It was admitted to New
and Nonofficial Remedies in 1907, before the Council had adopted the
present Rule 10, which provides that no article shall be admitted
to New and Nonofficial Remedies which, because of its unscientific
composition, is useless or inimical to the best interests of the
public or of the medical profession. In 1911 the Council considered
the question whether or not this product was still eligible and
decided in the end to retain it as probably having some merit. To
determine if Iodo-Mangan was eligible for New and Nonofficial Remedies,
1917, the Reinschild Chemical Company was requested to send in the
current advertising matter. As this advertising was not sent in and
as apparently the product was not marketed at the present time, the
Council on Pharmacy and Chemistry voted to omit Iodo-Mangan from New
and Nonofficial Remedies. At the same time the Reinschild Chemical
Company was informed that the preparation might be submitted for
reconsideration at any time.--(_From Reports of Council on Pharmacy and
Chemistry, 1916, p. 64._)
LIQUID ALBOLENE
Report of the Council on Pharmacy and Chemistry
As now marketed, Liquid Albolene (McKesson and Robbins, New York), is
claimed to be made only from genuine Russian oil and hence to possess
distinct advantages over
“... Oils purporting to be Russian, most of which are imperfectly
purified and many of which are positively dangerous for continued
use.”
On the other hand, a short time ago, McKesson and Robbins claimed that
Liquid Albolene was then available.
“... Of as high a quality as we had supplied before the European
War. Thanks to the research and scientific achievement of Our
Chemists, we are now able to offer LIQUID ALBOLENE, using as a base
a specially refined Domestic Oil that is in every way suitable for
medicinal purposes, and having the same viscosity as Russian Oil.”
The advertising matter suggests the promiscuous, thoughtless and
irrational use of Liquid Albolene and of a number of Albolene
preparations by extravagant claims, such, for example, as the following:
“Albolene will never fail to bring a free, easy stool, no matter
what condition may be present, from obstinate atony of the bowel to
fissure, fistula, or even malignant disease, and in spite of the
failure of ordinary purgatives to which the patient may have become
habituated....
“Aromatic Liquid Albolene is actually the first laxative presented
to the medical profession that seems to have no drawback....
“It will not have been lost upon the physician who has read the
remarks on the use of Aromatic Liquid Albolene to regulate the
bowels in surgical cases, that there are many instances where
it would prove equally valuable during the treatment of acute
diseases. In the exanthemata, in pneumonia, for example, to cite
only a few of the conditions where it may be used to advantage, an
absolutely reliable laxative that will not in any way weaken or
distress the patient, presents obvious superiority to any of the
agents heretofore in common use.”
The Council held Liquid Albolene ineligible because the product is
marketed in a way to encourage its indiscriminate and irrational use by
the public (Rule 4) and because unwarranted therapeutic claims are made
for it (Rule 6).--(_From Reports of Council on Pharmacy and Chemistry,
1916, p. 65._)
NAPHEY’S MEDICATED UTERINE WAFERS
Report of the Council on Pharmacy and Chemistry
Naphey’s Medicated Uterine Wafers were submitted to the Council by the
manufacturers, Naphey & Co., some years ago and were rejected. Naphey &
Co. has recently requested reconsideration of the preparation, and has
submitted advertising matter, trade packages and sample packages. The
label of the trade package contains the following:
“Naphey’s Wafers. For the local treatment of diseases of women,
indicated in catarrhal conditions of the vagina, and of the uterine
cervix. As a [_sic!_] adjuvant for the physician to use in carrying
out treatment of disease of the uterus.”
“Zinc Sulphate, 3-3/4 gr., Sodium Sulphate, 3-1/2 gr., Sodium
Borate, 4 gr., Boric Acid, 3/4 gr.”
“Naphey & Co., Warren, Pa., U. S. A.”
“Each box contains 25 wafers, sufficient for three months’
treatment. Price per box, 25c.”
In name, composition, and general appearance of the package, Naphey’s
Medicated Uterine Wafers bear a strong resemblance to Micajah’s
Medicated Uterine Wafers (The Journal, A. M. A., March 26, 1910,
p. 1070). An advertising pamphlet reads:
“In every form of leucorrhea Naphey’s Medicated Uterine Wafers are
indicated ...”
“What is true of leucorrhea is also true of all other functional
troubles affecting the female genital canal; they are all treated
best by astringents and antiseptics. And these, to be effective,
must be applied in prolonged contact.”
The implication that all “functional troubles affecting the female
genital canal” are best treated by astringent tablets like Naphey’s
Medicated Uterine Wafers is an absurdity. The naming of disease
conditions on the label, the manifestly unwarranted and exaggerated
therapeutic claims, the name, which is non-descriptive of composition
but suggestive of use, and the fixed formula, which cannot rationally
be expected to give uniformly satisfactory results in the wide range
of conditions for which the product is recommended, render Naphey’s
Medicated Uterine Wafers ineligible for New and Nonofficial Remedies
under Rules 4, 6, 8 and 10.
The report having been sent to Naphey & Co., the manufacturer
offered, on condition that the preparation be accepted, to revise the
advertising matter in minor particulars, to remove disease names from
the trade package and to adopt the name Naphey’s Wafers or Naphey’s
Tablets. The Council advised Naphey & Co. that the proposed names do
not conform to the requirements for acceptance in New and Nonofficial
Remedies because they do not indicate the composition of this
pharmaceutical mixture, and moreover, that the routine use of a complex
formula such as that of these tablets is irrational.--(_From Reports of
Council on Pharmacy and Chemistry, 1916, p. 66._)
NUJOL
Report of the Council on Pharmacy and Chemistry
Nujol, a liquid petrolatum (Standard Oil Company of New Jersey,
Bayonne, N. J.), was submitted to the Council by the manufacturers.
The Council advised the company that, before Nujol could be made
eligible for New and Nonofficial Remedies, the advertising claims made
for it must be revised to conform to the rules of the Council and the
term “liquid petrolatum” must be used in connection with the brand
designation and given equal prominence on the labels, advertisements
and all circulars. The company thereupon submitted a label on which
the name “Nujol” appeared in large red letters and under it in small
letters the words “Liquid Petrolatum.” This did not meet the Council’s
requirement with regard to the name. Moreover, Nujol continued to be
advertised to the public under exaggerated and unwarranted claims.
The foregoing report was sent to the Standard Oil Company of New
Jersey, which thereupon submitted revised advertising copy. This
copy was decidedly less objectionable than the previous advertising
but still contained exaggerated statements. The copy for use in
lay journals particularly evidenced exaggeration. Observation on
many occasions of a similar fact has convinced the Council of the
inexpediency of admitting to New and Nonofficial Remedies any article
which is advertised to the public.[101]
[101] Since publication of this report the Council on Pharmacy and
Chemistry has revised its rule against recognition of articles
advertised to the public so that this shall not apply (_a_) to
disinfectants, germicides and antiseptics, provided the advertising be
limited to conservative recommendations for their use as prophylactic
applications to superficial cuts and abrasions of the skin and to the
mucous surfaces of the mouth, pharynx and nose, and provided they are
not advertised as curative agents, and (_b_) to non-medicinal food
preparations, except when advertised in an objectionable manner.
The Council held that conflict with Rules 3, 6 and 8 prevented
the acceptance of Nujol and authorized the publication of this
report.--(_From Reports of Council on Pharmacy and Chemistry, 1916,
p. 68._)
PULVOIDS NATRIUM COMPOUND
Report of the Council on Pharmacy and Chemistry
Pulvoids Natrium Compound was submitted to the Council by the Drug
Products Company, Inc., New York, with the statement that each pulvoid
(coated tablet, said to be made to dissolve in the intestinal tract)
represents the equivalent of:
Potassium Nitrate 2-1/2 grs.
Sodium Nitrite 1/2 gr.
Sodium Bicarbonate 2 grs.
Fl. Ext. Crataegus Oxycantha 1 min.
Nitroglycerin 1/250 gr.
According to the advertisements the tablets are “indicated in the
treatment of high blood pressure and all forms of hypertension of the
cardio-vascular system.” It is claimed that the tablets “will not
irritate the kidneys.”
The Council, having submitted its objections to the manufacturer and
considered the firm’s reply, held that Pulvoids Natrium Compound was
inadmissible to New and Nonofficial Remedies for the following reasons:
1. The claim is made that the tablets disintegrate in the intestines;
experiments conducted by the Council indicated that in most cases they
would be broken up in the stomach. It was found that the tablets were
visibly changed immediately after being put into gastric juice or even
into distilled water; they disintegrated within from three to four
hours, not only in gastric juice (obtained from a dog) at 37 C., but
also in distilled water. It is quite usual for solids to remain in
the stomach for more than three hours. If they make their way out of
the stomach in less than that time the gastric movements must be so
vigorous as further to hasten the disintegration of the tablets.
2. The rules of the Council require that the name of a pharmaceutical
mixture shall indicate the potent ingredients. The name of this mixture
does not indicate the presence of the nitrites, the potassium nitrate,
the bicarbonate or the extract of hawthorne and the nondescriptive name
is likely to lead physicians to use the tablets without fully realizing
what they are giving.
3. No evidence was submitted that the tablets, as found on the market,
contained the amount of sodium nitrite and nitroglycerin claimed.
That is, it does not appear that the manufacturer checks the sodium
nitrite and nitroglycerin content by analysis. The Council did not
determine the nitrite content of the tablets. It maintains that when
a manufacturer places a product on the market the burden of proof is
on that manufacturer to show that the facts are in accordance with
his claims for his product. Further, the examination by the Council
of one or several specimens of any commercial product (particularly
in the case of nitroglycerin preparations) would not be a guarantee
of the constancy of its composition so long as the manufacturer does
not himself control the composition by analysis. The necessity of
such control of tablets containing nitroglycerin is evident from the
report[102] of L. F. Kebler of the U. S. Bureau of Chemistry. Dr.
Kebler said:
[102] J. A. M. A., Nov. 2, 1912, p. 1604.
“... nitroglycerin tablets have in a majority of cases been found
deficient in the nitroglycerin content declared.”
“... these commodities are manufactured largely by rule of thumb.
Little checking obtains in their manufacture and generally no
analyst is employed.”
A further proof that nitroglycerin tablets are likely to be deficient
in strength is contained in the convictions under the Food and Drugs
Act of manufacturers who sold tablets below the declared strength,
recorded from time to time (Notices of Judgments Nos. 3405, 2059, 1843,
1799).
4. There is no good evidence, experimental or clinical, to justify the
simultaneous administration in fixed proportion of two vasodilators
like sodium nitrite and glyceryl trinitrate (nitroglycerin). Also there
is no rational excuse for combining extract of hawthorne, which is said
to have a tonic effect on the heart muscle, with nitrites, which cause
relaxation of the vascular system, or for the combination with these
constituents of potassium nitrate or of sodium bicarbonate.
In the absence of evidence for the combination, Pulvoids Natrium
Compound must be considered an irrational mixture, the use of which is
a detriment to sound drug therapy and, hence, not admissible to New
and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and
Chemistry, 1916, p. 69._)
SALOFORM
Report of the Council on Pharmacy and Chemistry
A referee submitted the following report of the American Medical
Association Chemical Laboratory to the Council:
ANALYSIS OF SALOFORM
Saloform (Flexner) is advertised by the Robinson-Pettet Company of
Louisville, Ky. In the advertisements for the product it is stated that:
“Saloform is a definite chemical compound the component parts of
which are _Hexamethylene Tetramine_, _Salicylic Acid_ and Lithia.”
“As a Uric Acid Solvent it is indicated in _Rheumatism_, _Gout_, in
_Phosphaturia_, in _Gravel_, and in _Renal Colic_.”
“As a Genito-Urinary Antiseptic it limits suppuration anywhere
along the Urinary Tract, from the Kidneys down to the orifice of
Urethra.”
As, even after diligent search, no description of a compound of
hexamethylenamine (hexamethylenetetramine), salicylic acid and lithia
was found in chemical literature, it seemed probable that Saloform
is merely a mixture of hexamethylenamine and lithium salicylate.
Accordingly the separation of Saloform into its component parts by
means of selected solvents was attempted. By triturating the powder
with chloroform, filtering and evaporating the filtrate, a residue
was obtained which gave satisfactory tests for hexamethylenamine
but contained only traces of salicylic acid or lithium salicylate.
The portion insoluble in chloroform was dissolved in water. The
solution gave satisfactory tests for lithium salicylate but not for
hexamethylenamine. From these tests it is evident that Saloform
is a simple mixture of hexamethylenamine and lithium salicylate.
Quantitative examination indicated that the two ingredients,
hexamethylenamine and lithium salicylate, are present in approximately
equal amounts.
REFEREE’S RECOMMENDATION
The report of our Chemical Laboratory shows that Saloform is not a
definite compound as claimed, but a simple mixture of hexamethylenamin
and lithium salicylate. It is therefore in conflict with Rule 1. It is
also in conflict with Rule 6, for neither hexamethylenamin, lithium,
nor salicylate are therapeutically effective “uric acid solvents”; nor
would any of these have any effect on “phosphaturia.”
The mixture also conflicts with Rule 10; for it is inadvisable to
administer the ingredients in fixed, but unknown proportions.
It is recommended that Saloform be deemed inadmissible to N. N. R.
The Council adopted the recommendation of the referee and authorized
publication of this report.--(_From Reports of Council on Pharmacy and
Chemistry, 1916, p. 71._)
SECRETOGEN
Report of the Council on Pharmacy and Chemistry
About a year ago the Council declared Secretogen,[103] a product the
active ingredient of which was stated to be “pancreatic secretin” and
advertised as a remedy for certain conditions of defective digestion
and assimilation, to be ineligible for New and Nonofficial Remedies.
The reasons for this decision were stated at the time as follows:
[103] J. A. M. A., May 1, 1915, p. 1518.
“1. No evidence has been presented that the absence of secretin is a
cause of gastro-intestinal diseases. It is usually present, and if not
present, as in achylia gastrica, there is evidently some compensating
arrangement by which the pancreas is stimulated to perform its regular
functions.
“2. There is no evidence that secretin in any form is physiologically
active when administered by mouth.”
Since Secretogen was not the only so-called secretin preparation on
the market, and since the use of secretin preparations was recommended
by certain writers, notwithstanding the lack of evidence of its value,
the Council caused an experimental investigation of the question to be
made. This was carried out by Prof. A. J. Carlson of the University of
Chicago.
No secretin was found in the commercial products examined, namely,
Secretogen Tablets, Secretogen Elixir and Duodenin. Furthermore,
Carlson’s results[104] confirmed the Council’s previous conclusion
as to the inertness of secretin administered by mouth. The Council
endorsed Professor Carlson’s findings.[105]
[104] Carlson. A. J.; Lebensohn, J. E., and Pearlman, S. J.; Has
Secretin a Therapeutic Value? J. A. M. A., Jan. 15, 1916, p. 178.
Reports Council on Pharm. and Chem., 1915, p. 98.
[105] So-Called Secretin Preparations, J. A. M. A., Jan 15, 1916,
p. 208; Reports Council on Pharm. and Chem., 1915, p. 96.
The G. W. Carnrick Company has replied to the publication of this
report in the letter printed below. (A portion of this letter, which
consists of a communication from an unnamed correspondent of the G. W.
Carnrick Company and the company’s comment thereon, has been omitted.)
The Council offered to publish this if the Carnrick Company would
furnish the name of the writer. This it has not done. As will be seen,
the company now shifts ground, abandoning entirely the claim that
Secretogen contains secretin. The Council has authorized publication
of the letter (omitting the part just mentioned), together with the
comment that follows.
W. A. PUCKNER, Secretary.
“_The Council on Pharmacy and Chemistry of the American Medical
Association._
“Gentlemen:--The opinion of the Council and the contribution by
Professor Carlson which appeared in The Journal of the American Medical
Association for Jan. 15, 1916, have been read by us with interest.
The column of Current Comment dealing with ‘Tiger-Bone Therapy and
Clinical Experience’ has appealed to our good nature and, under the
circumstances, our sense of humor.
“Professor Carlson seems to have quite well established that the
so-called secretin preparations do not contain secretin to any
appreciable extent, and that they are inert in laboratory experiments
on normal animals. At the same time, to do away with an apparent
discrimination on the part of the management of the Council, it would
have been well if Professor Carlson had included the so-called secretin
preparations belonging to another well-known firm which markets such a
product. This discrimination has already been referred to by us.
“Had Professor Carlson stopped at the determination of the therapeutic
availability of secretin given by mouth, his work might have been
accepted without comment, even if we should have thought it advisable
to object to the matter published by the Council. But the professor
went beyond his province entirely when, in commenting on the findings
obtained by using Secretogen clinically, he said: ‘It is, perhaps,
impertinent for laboratory men to comment on these clinical results.’
It is. His point was well taken and it is a profound pity that
Professor Carlson did not observe his own ruling.
“In the words of a correspondent of The Journal of the American Medical
Association, in discussing Professor Carlson’s criticism of Dr. Crile’s
‘Kinetic Drive,’ ‘it behooves the laboratory man to be circumspect in
his criticism of clinical theories, since going beyond the bounds of
well-established things weakens his position, not merely with reference
to the particular subject under discussion, but with reference to
clinical phenomena in general.’ Clinical results have definitely
established the value of Secretogen. As the matter now stands this
statement is beyond criticism.
“When Secretogen was first introduced we assumed that it depended on
secretin for results produced. In this assumption we were in good
company, as witnessed by the testimony of Moore, Edie and Abram when,
in the course of their investigations as to the value in diabetes
of _a secretin-bearing extract given by mouth_,[106] they said: ‘In
the majority of these cases ... there has been no appreciable fall
in the output of sugar ... in some of these negative cases there has
been noted, however, improvement in the digestion and, in certain
cases, the patient’s weight has increased.’ They also state that
the secretin-bearing product ‘_appears to stimulate the functional
activity_ of the duodenum.’[106] They give a most significant
report.[107] We quote from the paper as follows:
[106] All italics are ours. G. W. Carnrick Company.
[107] Bio-Chem. Jour. =1=:28, 1906.
“‘The patient had been under observation for six months before
treatment and the sugar was not reducible by diet. _Almost at once the
dyspepsia from which he was suffering was relieved and his general
nutrition improved to such an extent that he regained over eighteen
pounds in weight, which he had previously lost, and this improvement
was accompanied by complete recovery_ of his physical and mental
energies.’[106]
“Inasmuch as this improvement could not have been due to the contained
secretin it must have been due to some other principle contained
in the extract. Our experience and that of the physicians who have
used Secretogen establish the fact that Moore, Edie and Abram made
no mistake when they came to the conclusion that what they termed a
secretin-bearing extract stimulates the functional activity of the
duodenum and improves the digestion.
“When Professor Carlson was investigating Secretogen he must have
realized that he was dealing essentially with an extract of the
duodenal mucosa. It is, therefore, all the more surprising, considering
his extensive researches into the literature, that he should have
ignored the testimony of some of his own authorities, particularly
Hallion, as to the value of extracts of the duodenal mucosa in duodenal
insufficiencies. The meticulous carefulness with which this evidence
was avoided is hardly worthy of the best traditions of physiology, a
science which has truth for its first and last aim.
“Hallion in his ‘La Pratique de l’Opothérapie’ says that the ‘aims of
duodenal opotherapy are: 1, To supply deficient duodenal juice. 2,
Above all to stimulate and to relieve this organ--_notably to aid the
production of secretin_[4]--and so profit by the stimulating action
which duodenal extract exercises on the duodenal mucosa which action
we, Enriquez and myself, believe and have experimentally proved,
conforms to the general principles of opotherapy. 3, By means of the
production of secretin, to reinforce the biliary, pancreatic and
intestinal secretions. 4, To stimulate intestinal peristalsis.
“‘Principal indications: Intestinal dyspepsias, intestinal
autointoxications, certain forms of constipation and duodenal
insufficiency.’
“At the International Congress of Medicine, Madrid, 1903, Hallion
said that he felt justified in stating that _duodenal opotherapy
correctly carried out must be classed under the very best methods of
treating dyspepsia_.[106] The results had been satisfactory and, in
many cases, remarkable. It had been nil in a few cases but it had
never been harmful in any degree. He pointed out that Marfan was the
first to employ this substance clinically. Marfan had had particularly
excellent results in children of 15 months to 4 years suffering with
marked malnutrition, anorexia and constipation. _Marfan prescribed
the duodenal extract given in milk._[106] Hallion further remarks that,
as he is not a practitioner, he had had only one opportunity to test
duodenal opotherapy clinically. The case was that of a man of 26 years
with obstinate intestinal dyspepsia and severe constipation which had
persisted from childhood. This patient had been treated by enemas,
laxatives, diet, etc. _Treatment with duodenal extract resulted in
a complete cure._[106] Hallion points out _that the most satisfactory
aspect of duodenal opotherapy is the permanent effect produced_,[106]
which bears out his statement that these extracts have the power to aid
in the restoration of function and structure of an organ.
“This has been so well established that the principle is now embodied
in a law which is frequently referred to as ‘Hallion’s Law’: ‘Extracts
of an organ exert on the same organ an exciting influence which lasts
for a longer or shorter time. When the organ is insufficient it is
conceivable that this influence augments its action and, when it is
injured, that it favors its restoration.’
“In ‘La Pratique de l’Opothérapie’ Hallion points out that ‘the
opotherapeutic product which corresponds to the affected organ
represents in some way the stimulating and elective food for that
organ, and if we supply the organ with a food which is more complete
than it necessarily needs, the affected organ can exercise its elective
action and take up only those substances of which it is in need.’
“Hallion’s observations on this point are beautifully borne out by
the classic work of J. W. Draper, as reported in The Journal of the
American Medical Association, Sept. 26, 1914. This report gives results
in both laboratory and clinical experiments.
“In order to show that fed jejunal and ileac epithelium exercise
some special detoxicating power, not yet understood but definitely
recognizable, Draper fed a control series of dogs with intestinal
obstruction, experimentally produced, on emulsified cells of liver,
spleen, pancreas and muscle tissue. These animals lived a few hours
longer than not-fed controls, but Draper says that it is evident
that these cells had either no detoxicating action, or a very feeble
one compared with intestinal epithelium. He used jejunal and ileac
epithelium clinically in two instances: 1st, In a female dog which had
had ‘chronic stomach trouble’ for six months. When Draper saw her she
had had complete intestinal obstruction for five days, with symptoms of
tachycardia, extreme nervousness and great weakness in the hind legs.
Draper removed a pebble from her intestine but her condition was still
grave.
“She was immediately put on small-intestine epithelium derived from
two dogs of different breed. Draper says that from a long experience
with duodenally obstructed dogs, he should not have expected her to
recover, but the symptoms gradually subsided and she lived. The second
instance in which he used the epithelium therapeutically was in the
case of a man who suffered from an annular cancer of the intestine with
definite symptoms of obstruction. After the operation, and realizing
that the patient was in a desperate condition, he fed him an emulsion
of intestinal epithelium from a dog. The pulse improved and the patient
lived.
“Some of Draper’s conclusions are as follows:
“‘Autotoxemia in intestinal obstruction undoubtedly arises from an
interference with cellular reactions of the intestinal epithelium....
When small-intestine epithelial cells of healthy animals are _placed
in the stomach_[106] of duodenally obstructed animals, such animals have
lived nearly twice as long as not-fed controlled animals. This evidence
is strongly opposed to the bacterial theory of origin of toxins.’
“The point to be emphasized is this: If this emulsion of intestinal
epithelium had been fed to a normal dog and a normal man, what would
have happened? Absolutely nothing. On the other hand, given as it was
to a dog and a man in desperate need it exercised a potent effect.
“Abundant clinical testimony can be cited in support of the opinions
of Moore, Edie and Abram, Hallion, Marfan and Draper as to the value
of extracts of the intestinal mucosa given by mouth in pathological
conditions. We have previously cited the published favorable opinions
of such gastroenterologists as Anthony Bassler, Lewis Brinton, G. R.
Lockwood, and R. C. Kemp, so there is no need to recapitulate their
experiences with what they honestly believed to be secretin-bearing
extracts, but which were essentially extracts of the duodenal mucosa.
“Supplementing the evidence of these men as to the value of these
extracts we submit an excerpt from a letter from one of the best known
physicians of Edinburgh:
“‘I can speak in very high praise of Secretogen, which I have used in
both tablet form and as the elixir. There is no doubt about its value
in a certain class of intractable indigestion which refuses to be
benefited by any other remedy. On several occasions I have been much
gratified by the definite relief obtained in this class of cases. It
hits the mark also in some types of obstinate constipation--I think
those cases where the trouble is wrapped up in impaired enervation
of the intestine, and where stasis occurs at certain segments of the
canal.’
“Hallion very pertinently points out[108] that it is now accepted that
opotherapy is not substitutive, but homostimulative and he remarks
further that it is well to bear in mind that the so-called active
substances which make the extract efficacious need not necessarily be
the hormones. ‘It may be the elements of tissue structure which may
come to the aid of the injured organ. The hormone should not therefore
be looked on as the only active agent of opotherapy and, while its
action is important, it need not necessarily be preponderant. The
chemical isolation of the hormones is, of course, of interest but may
not be as vital to organotherapy as we have thought.’ ...”
[108] Presse Médicale, 1912, p. 433.
COMMENT BY THE COUNCIL ON PHARMACY AND CHEMISTRY
The G. W. Carnrick Company, which formerly claimed that Secretogen was
efficacious because it contained secretin, now admits this claim to be
unfounded. Notwithstanding, the manufacturers still call their product
Secretogen and make for it practically the same therapeutic claims as
before. They now base these claims on vague “principles of opotherapy”
and on so-called “clinical testimony.” The burden of proof rests on
them to show that these old claims, already discredited but put forth
again on new grounds, are justified. Have they done so?
The “clinical te stimony” is not convincing. So much of it as is
definite enough to permit of criticism has already been dealt with. The
remainder consists of mere assertions; it is not through reliance on
such evidence that the Council can discharge its trust. On this side of
the question there is nothing new to be said--reassertion of a refuted
argument does not constitute fresh proof.
Nor is the case better on the experimental side. The statements of
Hallion, Enriquez, Zuelzer and others[109] as to the existence of a
“peristaltic hormone” not only have failed of confirmation, but also
have been positively discredited. With regard to Draper’s work, which
dealt with acute intestinal obstruction, it is difficult to see what is
its relevance to the present issue, particularly since Draper’s results
were obtained with a product derived from the mucosa of the jejunum
and ileum and _not with an extract of the duodenum_ such as Secretogen
purports to be.
[109] Cf. interal. Schagindweit, E.: Experimentelle Versuche mit
Hormonal, Arch. Internat. de Pharmacod., 1913, p. 77.
The innuendo that the Council discriminates in favor of certain
manufacturers, is itself a confession of weakness.
In publishing this correspondence the Council’s sole object is to put
the medical profession in possession of the exact facts of the case.
These may fairly be summed up as follows:
1. Secretogen was originally marketed as a preparation containing
secretin. None was found in it.
2. Notwithstanding proof of this fact, the G. W. Carnrick Company
retain the original name of the product, knowing that, by its
association with their former erroneous assertions concerning
Secretogen, this name must inevitably convey to a physician using
the product the impression that he is administering secretin. In the
advertising literature no hint is given that this original statement
was erroneous.
3. The product called “Secretogen” has not been shown, either
experimentally and by sound clinical evidence, to possess useful
therapeutic properties.
Under these circumstances the Council reaffirms its decision.--(_From
Reports of Council on Pharmacy and Chemistry, 1916, p. 72._)
IRON CITRATE GREEN
Report of the Council on Pharmacy and Chemistry
H. K. Mulford Company and E. R. Squibb and Sons submitted to the
Council ampules containing solutions of iron citrate green. It thus
became necessary to consider the eligibility of iron citrate green
itself for admission to New and Nonofficial Remedies. As the rules of
the Council provide that nonessential modifications of official or
nonproprietary preparations will not be recognized, the above named
firms were asked to state what advantages, if any, the so-called iron
citrate green had over the official iron and ammonium citrate. In reply
the H. K. Mulford Company wrote that it had come to the conclusion that
iron citrate green and ampules thereof would undoubtedly be considered
by the Council as a nonessential modification of an official product,
adding:
“It seems to differ from the official ferric citrate so far as
essentials go only in color, but custom, which is exceedingly hard
to change in South America, demands that this green variety of
ampules be used in place of the official product.”
In reply to a similar letter of inquiry E. R. Squibb and Sons wrote:
“Iron citrate green (iron and ammonium citrate green) differs from
the U. S. P. iron and ammonium citrate in that it contains less
iron and more citric acid and more ammonium citrate than does the
latter. It is of course a modification of the official salt and is
supplied to meet a real demand. Its reaction is quite decidedly
acid and our present stock contains Fe slightly below the U. S. P.
requirements for iron, assaying 15.74 per cent. instead of 16 per
cent. Fe. The tests used to control its quality are those for the
official product except as before indicated, it is always acid
instead of neutral, as the U. S. P. requires for that salt.”
The smaller iron content (98 per cent. of the U. S. P. requirement)
of the green variety referred to by E. R. Squibb and Sons is so small
as to be negligible. Further, the low iron content as well as the
acidity of the green salt would appear to be detriments rather than
advantages. Inasmuch as no evidence has been presented to show that
iron citrate green is superior in any way to the well-known iron and
ammonium citrate the Council held that iron citrate green, and with it
the dosage forms, was ineligible to N. N. R.
The preceding report was submitted to the Mulford Company and to E. R.
Squibb and Sons for comment before publication. The former firm replied
that in the present case it felt bound to supply the existing demand,
the latter replied that, to give the Council its support in this
matter, the sale of iron citrate green and ampules thereof would be
discontinued.--(_From The Journal A. M. A., Jan. 13, 1917._)
ASPIRIN
Report of the Council on Pharmacy and Chemistry
The referee’s report on Aspirin-Bayer which follows was submitted to
the Council and adopted by it and, in accordance with the referee’s
recommendation, was sent to the Bayer Company, Inc. The company’s reply
contained nothing to warrant the continued recognition of this product
by the Council. It was accordingly directed that Aspirin-Bayer be
omitted from New and Nonofficial Remedies.
W. A. Puckner, Secretary.
REFEREE’S REPORT
The referee’s attention has been called to the systematic campaign
of advertising aspirin to the public. He is informed that tablets
have been marketed for some time in “vest-pocket” boxes, bearing the
name “Aspirin” permanently affixed, which is in technical conflict
with the Council’s rule against indirect advertising to the public.
More recently, conspicuous advertisements have appeared in daily
papers. These are technically in conflict with the rule against direct
advertising to the public.
In addition to the plain technical conflicts with the Council’s rules
there is a feature of the case which has not hitherto been raised
and which should be fully considered: It may be remarked that the
advertisements contain no therapeutic recommendation, and do not, on
their face, urge the public to employ aspirin but apparently merely
tell the public how it may protect itself against sophistication.
In substance, they say: “If you are a user of aspirin, this is how
you may obtain the genuine.” It might be said that this is not an
attempt to increase the use or sale of aspirin--the ordinary object of
advertising--but that the means of protection against adulteration is
a “subject on which the public should be instructed.” The principle
of such exceptions is stated in the comments to Rule 3 (New and
Nonofficial Remedies, 1916, p. 15); and although the present case does
not come under the exceptions specified under these comments, it may be
urged that the exceptions need to be increased as occasion arises. The
notorious adulteration of aspirin may well be urged as establishing a
need for a similar exception in its use.
The general principle of protecting the public against fraud,
adulteration and substitution is directly in line with the objects of
the Council, and deserves commendation and support. It is obvious,
however, that the means adopted for this end must be efficient,
that they must not open the door to other, perhaps greater evils
and that they must be used in good faith. The policy of advertising
“Aspirin-Bayer” must be examined in these respects.
In the first place, the acceptance of a product by the Council implies
an agreement by the manufacturers or agents that they will adhere
strictly to the Council’s rules and will not depart from the letter or
spirit of these rules without notice to the Council. This principle has
been grossly infringed in the present case. There can be no doubt that
the agents were aware that their advertisements conflicted, at least
with the letter of Rule 3. Nevertheless, they did not, in any way,
inform the Council of the change in policy. In this respect, at least,
they have not acted in good faith.
Secondly, the wording of the advertisement implies that only the
tablets stamped with “The Bayer Cross” are genuine. This is misleading,
since every druggist has the right to make unstamped tablets of
aspirin, fully as genuine as those stamped with the cross.
Thirdly, the cross itself cannot be considered an efficient protection;
for people who imitate aspirin will not hesitate to imitate the
stamp. The remedy, in either case, and as with any other drug, is the
examination of trade samples, and the vigorous prosecution of those
guilty of violating the law.
Fourthly, the permanent affixing of the name “Aspirin” to the
vest-pocket boxes is also inefficient as a protection, and serves
mainly as an advertisement.
Fifthly, whatever may have been the motives of the advertisers, and
however carefully the advertisements are worded, they will inevitably
tend to increase the use of aspirin by the public, and this is directly
against the interests of public health. The public does not know, as
physicians do, that headaches are merely symptoms of other, sometimes
very serious conditions; and that they are often the signal for the
need of a thorough physical examination and diagnosis. It is true that
they are often also the symptoms of very minor derangements, which will
right themselves spontaneously; and that, in such cases, drugs like
aspirin may give relief and may do no harm. The patient, however, is
not educated to distinguish one class from the other, and therefore
anything that tends to promote the indiscriminate use of such remedies
as aspirin is detrimental to the public health. Furthermore, aspirin
itself is not always harmless. Alarming idiosyncrasies are sufficiently
common that the use of the first doses, at least, should require
medical supervision. With these considerations in mind, the referee is
of the opinion that the direct and indirect advertising of aspirin is
to be condemned.--(_From The Journal A. M. A., Jan. 20, 1917._)
PIL. CASCARA COMPOUND-ROBINS
Report of the Council on Pharmacy and Chemistry
A circular issued by the A. H. Robins Company of Richmond, Va.,
contains the following statement:
“PIL. CASCARA COMPOUND-ROBINS is a rational therapeutic formula,
composed of CASCARA, PODOPHYLLIN, COLOCYNTH and HYOSCYAMUS, which
promotes a natural flow of secretions, which is, in turn, the
physiologic stimulant of peristalsis. Thus, a normal evacuation is
produced without subsequent inhibition.
“They contain no Mercury, Strychnia nor Belladonna.
“An ideal aid to any remedial agent, when a Mild, Medium or Strong
alimentary stimulant is needed [_sic_].
“Made in two strengths, the dosage may be easily regulated so as
to obtain the effects of an Anti-Dyspeptic, Aperient, Laxative or
Cathartic, as desired. They never cause discomfort unless given in
larger dose than needed.”
This preparation is another example of the innumerable mixtures of
well-known drugs having nothing in the way of originality or of special
therapeutic value to recommend them.
The advertising implies that this particular combination has a special
action on the secretions of the gastro-intestinal tract; otherwise
it would be hard to explain the claim that the preparation is
antidyspeptic, if that means anything more than a laxative or cathartic.
The claim is made that this preparation contains no belladonna--yet
it admittedly contains hyoscyamus! This manifests either ignorance on
the part of the manufacturers, or an effort to impose on the medical
profession. Both belladonna and hyoscyamus contain variable amounts
of similar alkaloids, chiefly hyoscyamin. Hyoscyamus is feebler
than belladonna in its action, as it contains less alkaloid. The
qualitative differences between the two drugs, with reference to their
use as laxatives, is so slight as to make the company’s claim for
hyoscyamus appear either deliberately misleading or to be the result
of crass ignorance. Promoting this mixture of well-known laxatives and
cathartics as an “ideal aid to any remedial agent when a mild, medium
or strong alimentary stimulant is needed” is a slur on the intelligence
of physicians.
Pil. Cascara Compound-Robins is not acceptable for New and Nonofficial
Remedies.--(_From The Journal A. M. A., Jan. 27, 1917._)
CASTA-FLORA
Report of the Council on Pharmacy and Chemistry
Casta-Flora is one of those complex preparations which are offered
to the medical profession, with plausible arguments in support of
the claims made. It is put out by the Wm. S. Merrell Chemical Co.,
Cincinnati. Each fluidounce is said to represent:
“Castanea, fresh leaves, 40 gr.; Passiflora, fresh plant, 40 gr.;
Gelsemium, green tincture, 8 minims; Inula, represented by the
camphoraceous stearoptene Helenin, 20 grs.; Iodized Lime, 8 grs.;
Menthol, 1-4 grs.; Aromatic Syrup Yerba Santa, 60 minims.”
It is said to be:
“A new combination of well-tried remedies of especial value in
pertussis and other spasmodic coughs. It is composed of astringent,
antispasmodic, sedative and expectorant agents, that control the
paroxysms, relieve the irritation, promote expectoration, and give
tone to mucous membranes involved.”
Still more exaggerated claims are made for the individual constituents
of Casta-Flora, partly by direct statement, partly by inference. For
example:
“Castanea is almost a specific in whooping cough and other
spasmodic coughs.
“Passiflora is a narcotic, sedative and antispasmodic without
habit-forming properties, nor does it lock up the secretions and
upset digestion like opiates.
“Inula (elecampane) has been employed as a cough remedy in England
for centuries. Its action is similar to guaiacol and creosote. Its
active principle, helenin, is destructive of tubercle bacilli in
dilutions of 1 to 10,000.
“Iodized Lime, Menthol, and Yerba Santa are too well known as
expectorants and antiseptics to require more than passing mention.”
That Casta-Flora is a “new” combination may be admitted; it is
improbable that exactly this combination of obsolete drugs was ever
before selected for any purpose whatever, but the statement is
misleading in that no new principle of therapeutics is involved. On the
contrary, the combination is just what might be expected from haphazard
choosing of discarded and nearly forgotten drugs. It seems incredible
that a reputable firm of manufacturing pharmacists would make the
positive statement that castanea is _almost_ a specific in whooping
cough. Why not say it is a specific? It would be about as true. A
specific or “almost specific” for this disease would rank among great
medical discoveries; but castanea is merely a slightly astringent drug
neither better nor worse than scores of other astringent drugs that
have been tried, found valueless and discarded.
Hardly less surprising are the statements regarding passiflora. This
herb has been on the market about three quarters of a century. Not only
has it never established itself in scientific medicine, but it is not
even mentioned in modern standard works on therapeutics.
Of all the statements made in the circular perhaps the most remarkable,
in that it is so dangerously misleading, is that regarding helenin,
the active principle of elecampane. The statement that this principle
(helenin) is destructive of tubercle bacilli in dilutions of 1-10,000
can only mean that it is of extraordinary value in the treatment of
tuberculosis; in fact, it is definitely stated that the action of
elecampane is similar to that of guaiacol and creosote.
It is obvious that any drug which would destroy the tubercle bacilli in
the human lungs without exerting a toxic action on the patient would
be a great contribution to medicine. But although elecampane may have
been used for centuries it has proved to have little, if any, merit,
and even the National Standard Dispensatory, p. 848, says: “Elecampane
was formerly employed as a tonic, stimulant, diuretic, diaphoretic,
expectorant, and emmenagogue, but has now largely fallen into disuse.”
One looks in vain in the standard textbooks on therapeutics for a
description of the uses of inula (or elecampane), and of its so-called
“active principle,” helenin.
The circular to which reference has been made says, referring to the
use of castanea and passiflora in the treatment of whooping cough:
“Gelsemium, when made from the fresh, green plant--as is
Merrell’s--is an excellent adjuvant to the above drugs, and allays
the nervous irritability so frequently present.”
H. C. Wood, Jr. (Pharmacology and Therapeutics, 1916, p. 160), says of
gelsemium: “Gelsemium was originally employed as an arterial sedative
and febrifuge in the malarial fevers of the South, and subsequently
in sthenic fevers. It appears in some way to depress the bodily
temperature, but it does not appear probable that any advantage to be
derived from it will counterbalance the danger attending its employment
in the large doses required. In asthma, spasmodic laryngitis, whooping
cough, and nervous cough it has been recommended by Bartholow, but is
little used.”
That is about as favorable a statement for the drug as is to be found
in the textbooks, and it serves to illustrate how little new there is
in this mixture of obsolete drugs that Merrell seeks to market as one
possessing extraordinary therapeutic value.
Even though the ingredients, or certain of them, were singly useful in
the treatment of those conditions for which Casta-Flora is recommended,
no one could possibly foresee the effect in any given case of such a
jumble of drugs, both active and inert, as is said to be represented in
this preparation. The prescribing of such mixtures, the action of which
cannot in any way be foreseen, is plain charlatanism.
In addition, the various drugs in Casta-Flora are present in such
proportions that the dose of each of the several ingredients bears no
relation to the commonly accepted dose.
Casta-Flora is not acceptable for New and Nonofficial Remedies.--(_From
The Journal A. M. A., Jan. 27, 1917._)
FIRWEIN
Report of the Council on Pharmacy and Chemistry
Firwein is a product of The Tilden Company, New Lebanon, N. Y. It is
sold under the claim that when swallowed it has a “predilection” both
for the bronchial mucosa and also for the genito-urinary organs. To
quote:
“Expectorant, Sedative, Antispasmodic in the Treatment of
Inflammations of the Bronchial and Genito-Urinary Mucosæ.”
“Firwein being a bland, soothing balsam possesses a wide range of
adaptability and increased potency because of its healing virtues
and usefulness as an expectorant, sedative and antispasmodic in
bronchitis, and inflammation and catarrh of nose, throat and lungs.”
“Firwein has a special predilection for mucosæ, this being as
marked in diseases of the genito-urinary system as it is in the
respiratory organs. In inflammatory diseases of the genito-urinary
organs, its bland, curative properties are exerted in a gratifying
degree. In cystitis and uritis it is clearly indicated....”
Little information is given concerning the composition of Firwein. An
old circular says:
“Firwein contains Phosphorus, Iodin and Bromin finely blended with
a balsameous elixir made from the fir tree.”
From a more recent circular we quote:
“Firwein is prepared from the inside fresh green bark of the fir
tree ...”
The label on the product reads:
“Firwein is pleasantly and effectively blended with salts of iodin
and bromin, held in solution with 20 per cent. alcohol.”
The therapeutic claims made for Firwein and the mystery enshrouding
its composition make it obvious that the product is intended to appeal
to those who are either thoughtless or ignorant. This is emphasized by
the suggestion that Firwein be combined with (1) cod liver oil (under
the claim that it will “promote the efficiency of the oil”), with (2)
whisky for the treatment of bronchorrhea of the aged, and with (3)
syrup of hypophosphites for the treatment of persistent bronchitis.
As the composition of Firwein is secret, the therapeutic claims
unwarranted, and its use irrational, the Council declared it
inadmissible to New and Nonofficial Remedies.--(_From Journal A. M. A.,
Feb. 17, 1917._)
FIROLYPTOL PLAIN AND FIROLYPTOL WITH KREOSOTE
Report of the Council on Pharmacy and Chemistry
Firolyptol, another product of The Tilden Company, is, we are told,
composed of eucalyptol 10 drops, cottonseed oil 1/2 ounce and Firwein
enough to make 1 ounce. As the composition of Firwein is secret, it
is evident that the composition of Firolyptol is also unknown, except
to the manufacturers. “Firolyptol with Kreosote” is said to contain,
in addition to whatever may be the component parts of Firolyptol,
10 minims of creosote to each ounce. According to an advertisement,
Firolyptol with Kreosote is “antituberculous, antistrumous” and
“contains all the desired features of cod liver oil and is readily
assimilated.”
The advertisements of “Firolyptol Plain” and “Firolyptol with Kreosote”
seem to have for their key-note the assertion that cottonseed oil
is a particularly valuable nutriment and that when combined with
constituents of Firolyptol and Firolyptol with Kreosote becomes
particularly valuable to the tuberculous. To quote from an advertising
circular:
“Now that the reconstructive properties of cottonseed oil are
better appreciated by the profession, the advantages that follow
the administration of a palatable emulsion of this strengthening
and fattening food product are being demonstrated in hundreds
of cases where formerly reliance would have been placed in cod
liver oil.... A recent writer says that pure cottonseed oil is
the greatest and purest vegetable oil known to chemistry, and
will do much toward revolutionizing the treatment of the GREAT
WHITE PLAGUE.... If the treatment of tuberculosis could resolve
itself into the administration of a fatty substance in a readily
assimilated form, there would be no need for any part of FIROLYPTOL
but the Cottonseed Oil.... The toxic material constantly produced
in the system by the germs of tuberculosis tend to expose it
more and more to the ravages of the disease, and the physiologic
functions of the body suffer a constant depression. To neutralize
this germ activity with a consequent production of toxins it seems
most logical to employ such agents as have demonstrated their
suitability for such purposes, for which reason Eucalyptol and
Kreosote with Firwein are incorporated in FIROLYPTOL.”
The assertion that cottonseed oil is an especially valuable form
of fat is without warrant, but even if it were true the fat is
available in cheap and palatable forms in numerous other cottonseed
oil products. It is unnecessary to discuss the problematic value of
creosote in the treatment of tuberculosis or the value of eucalyptol
(now generally abandoned), or even of the secret mixture Firwein.
Food and fresh air, not drugs, constitute the fundamentals of the
treatment of tuberculosis, and it is both irrational and detrimental to
the interests of the tuberculous to administer various potent agents
in fixed and unknown amounts with such simple articles of food as
cottonseed oil. Neither of these products is acceptable for New and
Nonofficial Remedies.
Editorial Note.--Firwein[110] has been advertised to physicians
for twenty-five or thirty years and it is a sad commentary on the
intelligence of our profession that a preparation sold under such
obviously false and misleading, not to say silly, claims, should still
be in existence. Firwein is claimed to “prevent waste of tissue” in
tuberculosis. If it had this power, it would have found its place
long ago among the few great agents in drug therapy. As a matter of
fact, Firwein has gained virtually no recognition outside of the
“literature” of the Tilden concern. The claims made for Firwein are a
peculiar mixture of studied candor--when the truth is not likely to
hurt its sale--and inane vaporing--when the facts would not redound to
its credit. The Tilden Company declares that “Firwein stands without
a peer in its class.” But the company adds 10 drops of eucalyptol and
some cottonseed oil to this peerless product and an improvement is
born--“Firolyptol”! Then, to perfect the already perfectly perfected,
10 drops of creosote are added to “Firolyptol” and the profession is
offered “Firolyptol with Kreosote”! In just what verbal pyrotechnics
the Tilden Company might indulge, should it decide to add ten drops
of something else to “Firolyptol with Kreosote,” one shudders to
contemplate.
[110] Three other Tilden products have been the subject of deserved
and unfavorable comment in the J. A. M. A: “Narkine” in the issue of
Oct. 24, 1908, “Hydrocyanate of Iron-Tilden” in the issue of June 19,
1909, and “Febrisol,” in the issue of June 29, 1912. The first two
articles are reprinted in the latest (9th) edition of “The Propaganda
for Reform.”
If we are accused of exhibiting undue levity in discussing a
therapeutic problem, we can only answer that it is impossible to
consider seriously the Charlie Chaplins of the nostrum world.--(_From
The Journal A. M. A., Feb. 17, 1917._)
BINIODOL
Report of the Council on Pharmacy and Chemistry
In accordance with the usages of the Council, the report which
appears below along with the reports of the clinical investigation
by Drs. Cole and Keidel upon which the recommendations of the
referee were based were sent to the manufacturer for comment. The
reply of the manufacturer contained no evidence which justified the
Council in modifying the action already taken. Publication of the
report was therefore authorized.
W. A. Puckner, Secretary.
Biniodol was submitted to the Council by the manufacturer, Charles C.
Yarbrough, Memphis, Tenn. The manufacturer claims the product is a
solution of 1 per cent. of red mercuric iodid and 2.75 per cent. of
guaiacol in bland vegetable oil. It is marketed with the implication
that it is new and superior to other oil solutions of mercuric iodid.
For instance:
“... it is a straight solution of this mercurial compound, as
no alkaline iodide or other chemical is used to bring about the
solution.” “... It is probably the first and only one-percent oil
solution of straight mercury biniodide made in America....”
[The manufacturer, in a letter addressed to the secretary of the
Council, explains: “By straight solution, I mean that the solution
of the red mercuric iodid is effected without the aid of any
alkaline iodid or other chemicals.... Biniodol was first offered
early in 1912 ...”]
“Biniodol is, therefore, superior and much to be preferred to
other mercurials used for like purposes. It is highly active
therapeutically, producing the desired effects, usually without
the inevitable disadvantages of other mercurials. It rarely causes
salivation, diarrhea, or other symptoms of mercurial intolerance,
even when pushed to full therapeutic effect and when given for a
considerable period of time. Nor does it produce anemia.”
The Chemical Laboratory of the American Medical Association found that
Biniodol contained 1 per cent. of mercuric iodid and 2.5 per cent.
of guaiacol; hence the composition is essentially as claimed. It is
not true, however, that Biniodol is the “first and only one-percent
solution of straight mercury biniodide made in America.” As shown
in The Journal A. M. A., Dec. 9, 1914, p. 2247, formulas by Lemaire
and Dunning for making a “straight” solution of mercuric iodid were
published in this country in 1909 and 1910, respectively. Moreover, a
1 per cent. solution of mercuric iodid in oil is on the market and is
described in New and Nonofficial Remedies.
To determine whether or not Biniodol is “superior and much to be
preferred to other mercurials used for like purposes,” the Council
secured the cooperation of the Department of Dermatology and
Syphilology of the Western Reserve University cooperating with the
Cleveland City Hospital, and of the Johns Hopkins Hospital. Each
received three samples, labeled respectively, 1, 2 and 3: 1 contained
Biniodol; 2, a 1 per cent. solution of mercuric iodid in oil; 3, a
solution made up according to the formula of Biniodol, namely, 1 per
cent. of mercuric iodid and 2.5 per cent. of guaiacol in oil. All the
solutions were sterile. The investigators were not informed which
preparation was designated by the respective numbers, but they were
asked to use the preparations when intramuscular injections of a 1 per
cent. oily solution of mercuric iodid were indicated, and to note what
differences, if any, were observed following the use of the different
solutions regarding pain, discomfort, induration and any other
evidences of effects of the medicaments.
The Cleveland investigator reports that the patients were more or less
confused in their replies to inquiries and gave rather indefinite and
conflicting answers. After carefully tabulating the replies, however,
the following summary resulted:
1 was worse than 2 or 3 in 6 cases.
2 was worse than 1 or 3 in 5 cases.
3 was worse than 2 or 1 in 1 case.
The report from Johns Hopkins records a series of 117 injections
followed by the estimated reactions recorded below:
1. Severe, 13; mild, 14; none, 4; unrecorded, 8 = 39
2. Severe, 5; mild, 15; none, 16; unrecorded, 5 = 41
3. Severe, 7; mild, 25; none, 3; unrecorded, 2 = 37
That is, when recorded in percentages:
1. (Biniodol) severe, 33.3; mild, 35.9; none, 10.3;
unrecorded, 20.5.
2. (Without guaiacol) severe, 12.2; mild, 36.8; none, 39.0;
unrecorded, 12.2.
3. (With guaiacol) severe, 18.9; mild, 67.5; none, 8.1;
unrecorded, 5.5.
The manufacturer of Biniodol supplied the names of several physicians
who have used that preparation in their practice. Correspondence with
these elicited the following statements:
One had used Biniodol in forty-eight cases and states that “only a few
patients complain of pain at all and then only of a general soreness in
the muscle.” This physician reports a limited experience with the use
of another manufacturer’s “mercury biniodide oil solution” (apparently
six cases), but severe pain following the injections made it necessary
to abandon that preparation.
Another of these physicians named by the manufacturer, without
reference to any series of cases, reports that “Biniodol is superior to
any [oily solution of mercury biniodid] that I have tried.”
A third physician has “used it [Biniodol] a few times” and is
“convinced that it has no special action or virtue” over “any red
mercuric iodide in oil.”
This evidence, in its most favorable estimate, shows Biniodol to be
a good 1 per cent. solution of mercuric iodid in oil, but fails to
justify attributing to the preparation any unique characteristics. The
preparations made in the laboratory were as satisfactory, or better
than the Biniodol, and the presence or absence of the guaiacol was of
no consequence.
Biniodol conflicts with Rule 6, since claims of superior therapeutic
efficiency made for it are not established; and with Rules 8 and
10, since it is an unessential modification of an established
nonproprietary article marketed under a proprietary name.
In view of the foregoing, the referee recommends that Biniodol be
not accepted for New and Nonofficial Remedies, and that this report,
including the clinical investigations of Drs. Cole and Keidel, be
authorized for publication.
COMPARATIVE SYMPTOMS RESULTING FROM THE USE OF SEVERAL OILY
SUSPENSIONS OF RED MERCURIC IODID (MERCURY BINIODID)
Report of Dr. H. N. Cole[C]
[C] From the Department of Dermatology and Syphilology of the Western
Reserve University and of the Cleveland City Hospital.
At the request of Prof. Torald Sollmann of the Council on Pharmacy and
Chemistry of the American Medical Association, we made a comparative
study of several oily preparations of red mercuric iodid for
intramuscular injections in syphilis.
The information, concerning the preparations submitted to the
investigators, was as follows:
OILY SOLUTION OF RED MERCURIC IODID
“It is desired to ascertain whether there is any difference between
three preparations, each containing 1 per cent. of mercuric iodid, as
to pain, discomfort, induration, etc. The preparations will be labeled
“1,” “2” and “3.” They will be sterile.
“One of these preparations will be a plain solution in oil; another
will contain, in addition, 2.5 per cent. of guaiacol; the third will be
a proprietary preparation containing the guaiacol.
“It is also desirable to know how the oily solution compares with the
plain watery solution; but this is of secondary importance.”
The preparations all had the same appearance. The patients were taken
indiscriminately, and we attempted to keep them on the injections as
long as possible, in order to compare symptoms. Owing, however, to
discharge from hospital, symptoms of mercury intoxication, etc., we
were unable in all cases to give a thorough trial with each preparation.
In all, eleven patients were treated and seventy-one injections
given--by which time our experimental supply was exhausted.
In each case the drug was given intramuscularly in the buttocks and the
patients carefully observed for subjective symptoms of pain and for
objective symptoms of swelling, induration, abscess formation, etc. The
details are given in Table 1.
As will be noted, in several of the cases the patients were more or
less confused and gave rather indefinite and conflicting answers. In
attempting to compare the results from the different drugs, by careful
tabulation one finds that symptoms were more marked with the respective
sample as follows:
Preparation 1 was worse than Preparation 2 or 3 in six cases.
Preparation 2 was worse than Preparation 1 in two cases.
Preparation 2 was worse than Preparation 3 in five cases.
Preparation 3 was worse than Preparations 2 or 1 in one case.
TABLE 1.--DETAILS OF INVESTIGATION BY DR. COLE*
====+===+===+============+=======+======+===============+==============
| | | | | | Symptoms
| | | |Prepar-|Dose, +---------------+--------------
Case|Age|Sex| Date | ation | Grain| Induration-- | Objective
| | † | | | | Pain |
| | | | | | |
----+---+---+------------+-------+------+---------------+--------------
1 | 25| ♂ | 6/11/16 | 2 | 1/5 |None |Still painful
| | | 6/12/16 | 1 | 1/4 |None |None
| | | 6/13/16 | 2 | 1/5 |None |Quite painful
| | | 6/14/16 | 2 | 1/4 |Hurt for some |Very tender
| | | | | | time |
| | | 6/16/16 | 2 | 1/5 |Hurt for some |Very tender
| | | | | | time |
| | | 6/17/16 | 3 | 1/5 |Not so painful |Less tender
| | | | | | | than with
| | | | | | | Prepar-
| | | | | | | ation 2.
| | | 6/18/16 | 3 | 1/5 |Not so painful | Can sit on
| | |Discontinued| | | | area; as
| | |(salivation)| | | | needle prick
| | | | | | | is only place
| | | | | | | that it hurts
| | | 6/22/16 | 2 | 1/4 |Hurt, but not |Slight indur-
| | | | | | so long | ation and
| | | | | | | slight
| | | | | | | tenderness
| | | 6/24/16 | 2 | 1/4 |Hurt, but not |Pain “dead
| | | | | | so long | stinging”
| | | | | | | lasts 1 hour
| | | 6/25/16 | 1 | 1/4 |Not so bad |About the same
----+---+---+------------+-------+------+---------------+--------------
2 | 32| ♂ | 6/24/16 | 2 | 1/4 |Some pain |No induration
| | | 6/25/16 | 1 | 1/4 |More pain |Slight indur-
| | | | | | | ation
----+---+---+------------+-------+------+---------------+--------------
3 | ..| ♂ | 6/12/16 | 1 | 1/5 |No symptoms |Painful
| | | 6/13/16 | 2 | 1/4 |No symptoms |Painful
| | | 6/14/16 | 2 | 1/4 |Says the last |Painful
| | | 6/16/16 |Arseno-| | two have hurt |
| | | |benzol | | the more |
| | | 6/17/16 | 3 | 1/5 |More pain than |Small painful
| | | | | | previously | area
| | | 6/17/16 | 3 | 1/5 | |
| | | 6/18/16 | 3 | 1/5 |Not so much |Some indur-
| | | | | | pain: in | ation at site
| | | 6/19/16 | 3 | 1/5 | fact, patient | of injections
| | | 6/20/16 | 3 | 1/4 | says he is |
| | | 6/21/16 | 3 | 1/4 | over it in a |
| | | | | | very short |
| | | | | | while; com- |
| | | | | | plained of |
| | | | | | last one |
| | | 6/22/16 | 2 | 1/4 |Some pain |Considerable
| | | | | | | tenderness
| | | 6/24/16 | 2 | 1/4 |Not so much as | now after so
| | | | | | previously | many injec-
| | | 6/25/16 | 1 | 1/4 | | tions
----+---+---+------------+-------+------+---------------+--------------
4 | 36| ♂ | 6/22/16 | 2 | 1/4 |No pain |No tenderness
| | | 6/24/16 | 2 | 1/4 |Some pain |Some tender-
| | | | | | | ness
| | | 6/25/16 | 1 | 1/4 |Could not sleep|Some tender-
| | | | | | at night | ness; slight
| | | | | | | induration
----+---+---+------------+-------+------+---------------+--------------
5 | 32| ♂ | 6/20/16 | 3 | 20 |Some pain |No induration
| | | | |minims| |
| | | 6/21/16 | 3 | 25 |Some pain |
| | | | |minims| |
| | | 6/23/16 | 2 | 1/4 |Worse pain |No induration
| | | 6/24/16 | 2 | 1/4 |Worse pain |
| | | 6/25/16 | 1 | 1/4 |Worse than any |Slight tender-
| | | | | | |ness
----+---+---+------------+-------+------+---------------+--------------
6 | 20| ♂ | 6/ 8/16 | 1 | 1/6 |Very little |
| | | 6/10/16 | 1 | 1/5 |Very little |
| | | 6/13/16 | 1 | 1/4 |Very little |
| | | 6/14/16 | 2 | 1/4 |Bothered more |
| | | | | | than others |
| | | 6/17/16 | 2 | 1/5 |Quite a little |Still some
| | | | | | pain | soreness
| | | 6/18/16 | 2 | 1/5 |Quite a little |Still some
| | | | | | pain | soreness
| | | 6/19/16 | 3 | 1/4 |Considerably |Very little
| | | | | | less pain than| tenderness
| | | 6/20/16 | 3 | 1/4 | with Prepar- |
| | | 6/21/16 | 3 | 1/4 | ation 2 |
----+---+---+------------+-------+------+---------------+--------------
7 | 30| ♂ | 6/12/16 | 1 | 1/5 |Little pain |None
| | | 6/13/16 | 2 | 1/4 |No pain |
| | | 6/14/16 | 2 | 1/5 |Some pain |
| | | 6/16/16 |Arseno-| | |
| | | |benzol | | |
| | | 6/17/16 | 3 | 1/5 |Not so much |No tenderness
| | | 6/18/16 | 3 | 1/5 |Not so much |No tenderness
| | | 6/19/16 | 3 | 1/5 |Very little |Only slight
| | | | | | pain | amount of
| | | 6/20/16 | 3 | 1/4 | | induration
| | | 6/21/16 | 3 | 1/4 | |
| | | 6/22/16 | 2 | 1/4 |Some pain |Some little
| | | | | | | induration
| | | 6/24/16 | 2 | 1/4 |Considerable |Some indura-
| | | | | | pain | tion
| | | 6/25/16 | 1 | 1/4 |“Fine” |Slight indura-
| | | | | | | tion
----+---+---+------------+-------+------+---------------+--------------
8 | 28| ♂ | 6/13/16 | 2 | 1/5 |Little pain |Little pain
| | | | | | | afterward
| | | 6/15/16 | 2 | 1/5 |Little pain |Little pain
| | | | | | | afterward
----+---+---+------------+-------+------+---------------+--------------
9 | 28| ♀ | 6/17/16 | 2 | 1/5 |Some complaint |Very little
| | | | | | of pain. | induration
| | | 6/18/16 | 2 | 1/5 | Fairly severe |
| | | 6/19/16 | 3 | 1/5 |Some pain; says|Very slight
| | | | | | these have | induration
| | | 6/20/16 | 3 | 1/4 | hurt very much|
| | | 6/21/16 | 3 | 1/4 | less than |
| | | | | | others |
----+---+---+------------+-------+------+---------------+--------------
10 | 37| ♂ | 6/12/16 | 1 | 1/5 |No symptoms |None
| | | 6/13/16 | 1 | 1/4 |No symptoms |None
| | | 6/14/16 | 1 | 1/5 |No symptoms |None
| | | 6/15/16 | 3 | 1/5 |No symptoms |None
| | | 6/16/16 |Arseno-| | |
| | | |benzol | | |
| | | 6/17/16 | 3 | 1/5 |“Much less pain|None
| | | | | | than biniodid |
| | | | | | or grey oil” |
| | | 6/18/16 | 3 | 1/5 |No complaint |None
| | | 6/19/16 | 3 | 1/5 |Says he is over|Some indura-
| | | 6/20/16 | 3 | 1/4 | it in one hour| tion at site
| | | 6/21/16 | 3 | 1/4 | | of injection
----+---+---+------------+-------+------+---------------+--------------
11 | 30| ♀ | 6/11/16 | 1 | 20 |Considerable; |Considerable
| | | | |minims| not so much | pain and
| | | 6/12/16 | 2 | 20 | | tenderness on
| | | | |minims| | palpation
| | | | | | | over area
| | | 6/13/16 | 1 | 25 |Not much pain |Indurated area
| | | | |minims| | at pt. of
| | | | | | | each.
| | | | | | | Painful
| | | 6/14/16 | 1 | 25 |Not much pain |Slight indura-
| | | | |minims| | tion
----+---+---+------------+-------+------+---------------+--------------
* The diagnosis in Case 5 was primary syphilis, and in the other cases,
secondary syphilis.
† In this column, ♂ indicates male, and ♀ female. In no case did
Wassermann become negative.
The criticism may be raised that the number of cases and of injections
is too small to permit the drawing of any just conclusions. Even
should we grant it, the statistics certainly do not prove any marked
superiority of any one of the preparations over the others. We wish to
thank Dr. Sollmann for advising and directing us in this work, and Drs.
Bailey, Bernstein, Markus and Reycraft for assistance in carrying it
out.
Report of Dr. Albert Keidel
Twenty cases were chosen at random from the syphilitic patients
attending the clinic. They were given intramuscular injections of the
three solutions, in amounts varying from 1 to 2 c.c., at intervals (in
most instances) of two days. The injections were invariably made into
the gluteal muscles, at depths of from 2 to 2-1/2 inches, and ordinary
care exercised to preserve asepsis. After injection the patient was
allowed to depart, and the result was recorded at the succeeding
visit. The result was determined from the patient’s statement and our
examination. Some patients received injections of only one solution;
some were treated with first one and later with another, and one
patient received all three at different times. The solutions were never
mixed for a single injection, of course.
TABLE 2.--REACTIONS IN TWENTY CASES REPORTED BY DR. KEIDEL
==================================================================
Preparation Reactions Number of
┌────────────┴────────────┐ Injections
Severe Mild None Undetermined
1 13 14 4 8 39
2 5 15 16 5 41
3 7 25 3 2 37
---
117
------------------------------------------------------------------
The solutions are understood to contain a 1 per cent. solution of red
mercuric iodid in oil, two of them containing in addition 2.5 per
cent. of guaiacol, one of these being a proprietary preparation. The
solutions are designated as Preparations 1, 2 and 3, respectively,
corresponding to the numbers on the labels of the bottles in which they
were originally received. The local reactions are recorded as “severe”
(S), “mild” (M), “none” (O) and “Undetermined” (U). By “severe” is
meant very severe pain lasting for from several hours to several days;
by “mild” is meant slight pain or numbness for several hours, or less
than an hour; “none” indicates that there was no local reaction, and
“undetermined,” that the patient has failed to return after the last
injection.
In Table 3 all the details of the investigation are recorded. Under
“Local Reaction,” the letters represent the type of reaction after each
injection, in the order in which they were given; when two solutions
were used in the same case, the letters represent the reactions
following the solution opposite which they stand. In the fifth column
the plus and minus symbols indicate the Wassermann reaction; plus
indicates a completely positive, and minus a completely negative
reaction. When there is only one sign, it refers to the reaction at the
end of treatment; when there are two, to the reaction before and after.
The seventh column shows the clinical result at the end of treatment;
when no note is made, it means that there was no change noted. In the
eighth column are noted any objective results observed at the time of
examinations of the patients.
The injections were made and the result charted by Dr.
E. L. Zimmermann, of my staff, under my directions and
supervision.--(_Abstracted in The Journal A. M. A., Feb. 24, 1917._)
TABLE 3.--DETAILS OF INVESTIGATION BY DR. KEIDEL
====+===+=======+=========+========+======+=======+==========+==========+============
| | | | Total |Dura- |Effect | | |
Case|No.|Prepar-| Local | Amount | tion | on | Type of | Result | General
| | ation |Reaction |Solution| of |Wasser-| Case | | Remarks
| | | | Given, |Treat-| mann | | |
| | | | C.c. | ment | | | |
----+---+-------+---------+--------+------+-------+----------+----------+------------
1 | 3 | 2 | OOO | 3 | 6 da.| + |Latent | |
2 | 5 | 2 | MOSMS | 5.6 | 9 da.| + |Gummas....|Marked |
3 | 7 | 1 | MMM; | 9.5 | 3 mo.|- to + |Latent | improve- |
| | | others U| | | | | ment |
| 3 | 2 | UUU | | | | | |
4 | 1 | 2 | U | 0.75 | ... | + |Latent | |
5 | 4 | 1 | SSSM | 4.4 | 9 da.| - |Gummas....|..........|After 4th
| | | | | | | | | injection,
| | | | | | | | | developed
| | | | | | | | | diarrhea;
| | | | | | | | | melena
6 | 9 | 1 |OOUMSOSMU| 9.1 | 1 mo.| - |Latent | |
7 | 2 | 3 | MM | 3.8 | 2 da.| + |Latent |..........|Well
| | | | | | | | | tolerated
8 | 7 | 2 | OOOOMOU | 9.6 |17 da.|+ to + |Primary...|Primary |
| | | | | | | | healed |
9 | 4 | 1 | SMMU | 5.5 | 9 da.| |Gumma.....|Improved |
10 | 3 | 3 | MSS | 3 | 6 da.| + |Palmar |Markedly |
| | | | | | | syphilis;| improved |
| | | | | | | tertiary | |
11 | 7 | 3 | MSMMMMM | 10.6 |13 da.|+ to + |Latent | |
12 | 3 | 2 | MMO | 5.4 |14 da.| + |Secondary |Rash |Developed
| 2 | 1 | SM | | | | (papular)| disap- | toxic ery-
| | | | | | | | pearing.| thema on
| | | | | | | | | thighs.
| | | | | | | | | Cleared up
| | | | | | | | | on stopping
| | | | | | | | | HgCl₂ and
| | | | | | | | | under local
| | | | | | | | | treatment
13 |10 | 3 | MMMMMMMM| 12.6 |20 da.|+ to + |Secondary |Rash |Small
| | | MMU | | | | (lichen | not | induration
| | | | | | | syph.) | improved.| following
| | | | | | | | | injection
| | | | | | | | | of 1.2 c.c.
14 | 6 | 2 | OOMSMM | 7.2 |17 da.|+ to + |Old |..........|Responded to
| 2 | 1 | SM | | | | cerebro- | | doses of
| | | | | | | spinal | | 1 c.c. with
| | | | | | | syphilis | | salivation;
| | | | | | | | | fever after
| | | | | | | | | injection
| | | | | | | | | of 1.2 c.c.
15 | 4 | 1 | SOMS | 4.2 | 7 da.|+ to + |Secondary |No |
| | | | | | | (condyl- | improve- |
| | | | | | | omas) | ment |
16 | 9 | 3 |OMOMMSMSO| 10.4 |12 da.| + |Secondary |Pustules |Slight
| 2 | 2 | SO | | | | (pustular| dried up;| gingivitis
| | | | | | | syph.) | headache | following
| | | | | | | | and fever| dose of
| | | | | | | | gone | 1.5 c.c.
17 | 5 | 1 | SSMSU | 13.3 |18 da.|+ to + |Tertiary; |General |
| 2 | 2 | MS | | | | aortitis.| condition|
| 2 | 3 | MS | | | | | improved |
18 | 4 | 2 | OOMM | 9.5 |13 da.|- to + |Latent | |
| 2 | 1 | MM | | | | |Markedly |
| | | | | | | | improved |
19 | 2 | 3 | MU | 2.5 | 5 da.| + |Gumma.....| |
20 | 5 | 2 | MMMMO | 9 |14 da.|+ to + |Latent....|Marked |Small
| 2 | 3 | MS | | | | | general | induration
| | | | | | | | improve- | following
| | | | | | | | ment | No. 3
----+---+-------+---------+--------+------+-------+----------+----------+------------
CORPORA LUTEA (SOLUBLE EXTRACT), PARKE, DAVIS & CO.
Report of the Council on Pharmacy and Chemistry
Following inquiries, the Council took up for consideration “Corpora
Lutea (Soluble Extract),” marketed by Parke, Davis & Co. in the form of
ampules and proposed for hypodermic administration. The report which
appears below was submitted to the Council by a committee, and was
adopted by the Council. Corpora Lutea (Soluble Extract) was declared
inadmissible to New and Nonofficial Remedies, and publication of the
report authorized.
W. A. Puckner, Secretary.
Corpora Lutea (Soluble Extract) has not been submitted by the
manufacturer. The information of the referee is based, therefore, on
the claims made in the trade package, and on the statements in the
price list. These show that the product is essentially secret and
claims made for the actions and uses of the preparation do not make
clear the essentially experimental status of the article, and are
therefore misleading.
_Conflict with Rule 1._--No definite statement of composition appears
beyond the indefinite claim that it is an aqueous solution of “soluble
Corpora Lutea Extract,” each ampule corresponding to 0.2 Gm. of
desiccated gland. How these soluble products are obtained, whether they
represent _all_ the water-soluble principles, or whether some have been
eliminated, are questions that are not answered. Yet such information
is essential to intelligent and scientific use, for, as there is no
method of standardization, the method of preparation is the only mark
of identity. For instance, we do not know at this time whether proteins
have anything to do with the supposed value of corpora lutea. It is,
therefore, essential to know whether or not the proteins have been
eliminated.
_Conflict with Rule 6._--The circular in the package advises the
hypodermic use of this extract, not only in functional amenorrhea
and the ordinary reflex consequences of physiologic or artificial
menopause, but also in:
“‘neurasthenic’ symptoms during menstrual life”;
“sterility, not due to pyogenic infection or mechanical
obstruction”;
“repeated abortions, not due to disease or mechanical factors”;
“hyperemesis in the early months of pregnancy.”
These are not stated merely as conditions in which various enthusiasts
have tried corpus luteum, but as conditions “for which it will be found
serviceable.”
It is not necessary to inform the medical profession that this
statement is calculated to raise expectations which cannot possibly be
fulfilled. Even the manufacturers seem to realize this; at least they
speak somewhat indefinitely of “suitable cases,” “good judgment,” “real
indications,” etc. But they proceed to nullify this warning--if it was
intended as a warning--by their illustrations of unsuitable cases,
for instance, “amenorrhea due to extreme anemia, dysmenorrhea due to
cervical stenosis,” etc. Finally, they sum up the case:
“Therefore, additional emphasis on the necessity for the proper
selection of cases is essential in order that this useful
preparation may not be unjustly discredited.”
How these cases of sterility, abortions, etc., are to be selected
is not revealed. In other words, the restriction is no more than a
convenient device by which every improvement is to be attributed to the
medicine, and every failure to the physician.
The referee recommends that Corpora Lutea (Soluble Extract), Parke,
Davis & Co., be held ineligible to N. N. R., because it is a secret
preparation advertised under extravagant claims.
[Editorial Comment.--Was it not in Weir Mitchell’s “Adventures of
François” that the itinerant promised to pull teeth without any
pain, _if the patient would hold absolutely still_? And, _mirabile
dictu_, the ones who suffered were those who had not held absolutely
still!]--(_From The Journal A. M. A., April 7, 1917._)
WHEELER’S TISSUE PHOSPHATES
Report of the Council on Pharmacy and Chemistry
The Council held that the contribution from the A. M. A. Chemical
Laboratory, “Wheeler’s Tissue Phosphates,” demonstrates that this is a
semisecret, complex and irrational preparation, sold with misleading
claims concerning its medicinal constituents and therapeutic properties.
The Council directed that the report be included with the Annual
Council Reports and declared Wheeler’s Tissue Phosphates in conflict
with Rules 1, 6, 8 and 10.
W. A. Puckner, Secretary.
WHEELER’S TISSUE PHOSPHATES
L. E. Warren, Ph.C., B.S.
“Wheeler’s Tissue Phosphates,” known also as “Compound Elixir of
Phosphates and Calisaya,” is advertised as a nerve food and a
nutritive tonic. The label states that it contains calcium, iron,
sodium trihydrogen phosphates, alkaloids of Peruvian bark with 12-1/2
per cent. of alcohol. The preparation is sold by the T. B. Wheeler,
M. D. Co., of Rouses Point, New York. According to the manufacturer,
Wheeler’s Tissue Phosphates
“... is an _inorganic_ combination of the phosphates of iron and
calcium and hydrogen (phosphoric acid) together with hydrochloric
acid, hydrocyanic acid, and quinine, cheerful coloring, and a
delicious, cordial-like flavoring.”
“... The iron is the green, inorganic phosphate and the calcium the
simple white phosphate of your early student days....”
The preparation is a red liquid, having an acid reaction, a
sweet-bitter taste and the odor of wild cherry. Qualitative tests
indicated the presence of calcium, iron, a phosphate, a chlorid, a
sulphate, quinin or cinchona alkaloids, alcohol, sodium, cochineal
coloring and invert sugar. Ammonium salts, glycerol, citrates or
lactates were not found. From the quantitative values obtained the
preparation may be taken to represent:
Sp. gr at 25C./25C. 1.1087
Alcohol (per cent, by volume) 11.35
Gm. per 100 c.c.
Calcium phosphate [Ca₃(PO₄)₂]* 0.397
Iron phosphate (FePO₄.4H₂O)* 0.068
Chlorid (as hydrochloric acid) 0.407
Sodium sulphate (Na₂SO₄.10H₂O) 0.043
Quinin sulphate (U. S. P.) 0.041
Sodium phosphate (Na₂HPO₄.12H₂O) 0.065
Invert sugar 26.824
Water, cochineal and flavor, to make 100 c.c.
* It should be understood that the calcium and iron salts are held in
solution by the hydrochloric acid.
The dose of Wheeler’s Tissue Phosphates recommended by the manufacturer
is a tablespoonful or about 15 c.c. (1/2 oz.). The total calcium in a
dose of the preparation is equivalent to about one-sixth of an average
dose of the official calcium chlorid, and the total phosphate to each
dose is equivalent to about one-fourth of a dose of the official
diluted phosphoric acid. Each prescribed dose of the preparation
contains about 0.01 gm. (2/13 grain) of iron phosphate or about one
twenty-fifth of the average dose, and to obtain a Pharmacopeial dose of
iron phosphate the patient would be obliged to take three-fourths of
the contents of an entire bottle--or 12 ounces--of the preparation. If
it be assumed that all of the chlorid present is in the form of free
hydrochloric acid, each dose of the preparation contains the equivalent
of about two-thirds of one Pharmacopeial dose of diluted hydrochloric
acid. Each dose of the preparation contains about 0.0062 gm. (1/10
grain) of quinin sulphate, or about one-sixteenth of the average tonic
dose. In other words, to obtain the amount of quinin sulphate given in
the U. S. Pharmacopeia as the tonic dose, the patient would be required
to swallow 7-1/2 fluidounces of the proprietary preparation, or the
contents of nearly half a bottle. The fallacy of prescribing Wheeler’s
Tissue Phosphates either for its quinin or its iron content is apparent.
Wheeler’s Tissue Phosphates is, then, a mildly bitter flavored syrup
which contains nearly 12 per cent. of alcohol, small quantities each of
calcium phosphate and hydrochloric acid and insignificant amounts of
iron and quinin salts. In other words, essentially it is a sweetened
solution of small quantities of calcium phosphate in very dilute
hydrochlorid acid together with 12 per cent. of alcohol.
Bearing in mind the analysis of the preparation, how ludicrous some of
the claims appear:
“_Tissue Phosphates_ is not a hypophosphite preparation; it is
not a combination of glycerophosphates or other organic salts, or
so-called peptonates and manganates, all recently condemned by
the best therapeutic opinion here and in Europe, as much slower
and less active than the simpler salts. The iron is the green,
inorganic phosphite and the calcium the simple white phosphate of
your early student days. Nature takes these simple salts and builds
them rapidly into lecithin, bone, and other tissue, without the
delay incurred by splitting up the organic salts before she can
recombine them.”
“Tissue phosphates is in fact a _chemical food_.”
“The formula, suggested by Professor Dusart, of Paris, combines in
an easily assimilable and agreeable cordial; medium medicinal doses
of Phosphorus, the Generator of Nerve Force; Calcium Phosphate,
for Cell Development and Nutrition; Sodium Phosphate, a stimulant
of Liver and Pancreas and Corrective of Acid Fermentation in the
Alimentary Canal; Iron, generating in the Blood, Heat and Motion,
Phosphoric Acid, Tonic in Sexual Debility; Alkaloids of Calisaya,
Antimalarial and Antipyretic; Extract of Wild Cherry, Tonic, yet
Calming Irritation and Diminishing Nervous Excitement; Ethyl
Alcohol 12.5%; and Aromatics.”
Although the claim is made that the “formula” of Wheeler’s Tissue
Phosphates has been “suggested by Professor Dusart,” such of Dusart’s
papers as were available in this country[111] failed to disclose any
“formula” that was at all comparable to this product.
[111] Dusart, L.: Recherches expérimentales sur le rôle physiologique
et thérapeutique du phosphate de chaux, Paris, 1870; Quel est l’acide
du suc gastrique? Lille, 1874, unbound, 8 pages; Notice sur l’emploi et
les proprietés du lacto-phosphate de chaux, Clichy, 1868, unbound, 8
pages. Dusart and Blache: Recherches sur l’assimilation du phosphate de
chaux, Paris, 1868, unbound, 15 pages.
[Editorial Note.--The investigation verifies facts that must be obvious
to every physician who has given the matter thought. “Wheeler’s Tissue
Phosphates” is an unscientific, shotgun mixture whose most active and
powerful drug is the alcohol it contains. That it was not years ago
relegated to the realms of obsolete and discarded preparations is a
commentary alike on the lack of scientific discrimination and the
persuasive power of advertising. While in the past “Wheeler’s Tissue
Phosphates” has been advertised extensively in medical journals,
it seems that now the chief, if not the only beneficiary of the
advertising appropriation for this product is the _New York Medical
Journal_, which weekly heralds the “Delicious” and “Sustaining”
qualities of “The Ideal Tonic for Fastidious Convalescents.”]--(_From
The Journal A. M. A., May 5, 1917._)
THE CLAIMED GALACTAGOGUE EFFECTS OF NUTROLACTIS
AND GOAT’S RUE NOT SUBSTANTIATED
Report of the Council on Pharmacy and Chemistry
Specific lactagogues--drugs which stimulate the secretion of
milk--are unknown to science. Yet medical publications give space
to advertisements of a proprietary--“Nutrolactis”--which is said to
increase the milk supply of nursing mothers. Since dependence on
a preparation of this kind is likely to cause neglect of the only
means of increasing a scanty milk supply of nursing mothers--care of
the general health and a sufficient quantity of proper food--this
proprietary and the drug “goat’s rue,” (_Galega officinalis_) which the
proprietors hint as being the potent constituent, were subjected to a
critical study to determine their possible influence on milk secretion.
For this purpose the Council secured the help of A. J. Carlson, Ph.D.,
professor of physiology, University of Chicago. Dr. Carlson, with
the aid of A. Woelfel, M.D., and Marian Lewis, Sc.M., undertook to
estimate the effect of Nutrolactis and of goat’s rue on nursing dogs
and goats with the intention of extending the study to nursing mothers
if the animal experiments so warranted. The contribution, “The Alleged
Galactagogue Action of Galega and Nutrolactis,” by Marian Lewis and
A. J. Carlson from the Hull Physiological Laboratory of the University
of Chicago, which appears below, shows that Nutrolactis and goat’s rue
are without influence on the milk secretion in nursing animals.
The Council endorsed the work of Lewis and Carlson and held that the
claimed galactagogue effects of Nutrolactis and goat’s rue are not
substantiated.
W. A. Puckner, Secretary.
THE ALLEGED GALACTAGOGUE ACTION OF GALEGA AND NUTROLACTIS[D]
Marian Lewis, Sc.M., and A. J. Carlson, Ph.D.
CHICAGO
[D] From the Hull Physiological Laboratory of the University of Chicago.
[D] This investigation was begun in 1915 by Drs. A. Woelfel and A. J.
Carlson.
It is well established that the food best adapted to the energy and
growth requirements of the infant is normal mother’s milk. Any decrease
in quantity or deterioration in quality of the maternal secretion is
soon followed by a parallel impairment of growth, loss of weight,
or lowered resistance to infection in the infant. The widespread
occurrence of deficient milk secretion is a matter of common knowledge.
The discovery of true lactagogues, or specific substances which
increase the quantity and quality of the milk on being administered to
nursing mothers, would therefore be of very great importance. In view
of this great medical and economic interest in true lactagogues it is
not surprising to find that the medical and biologic literature records
discoveries of lactagogues based on hope rather than demonstration, and
that spurious lactagogues are on the market.
Some of the factors known to affect milk secretion are general health,
food supply, psychic state, and heredity. The mechanism of secretion
and the method by which these factors affect it are imperfectly
understood. In general it has been observed that milk yield improves
both in quantity and in quality with improvement in general health,
better food supply, and more favorable psychic state. The influence of
heredity is taken advantage of by dairymen who are well acquainted with
the potential milk production of the different breeds of cattle.
Among the substances which have been reported to stimulate milk
secretion may be mentioned the extract of the posterior lobe of the
hypophysis. But pituitary extract is not a true lactagogue, because
its action is confined to the smooth musculature of the gland ducts,
causing a more or less complete ejection of the milk already formed;
it has no effect on the gland cells or the actual secretory process in
the direction of increasing the milk yield. Extracts of thymus, corpus
luteum, ovaries, uterus, placenta, fetus, and the mammary gland itself
have also been reported to have a temporary stimulating effect on the
quantity of milk secreted, but when these extracts are given by mouth
they are apparently without specific influence on the mammary gland.
Galega, or goat’s rue (_Galega officinalis_), is an herb described in
the National Formulary as being slightly bitter and astringent. In
1873, Gillet-Damotti,[112] in a communication to the French Academy,
stated that this plant when fed to cows increases the secretion of
milk from 35 to 50 per cent. Other French writers have affirmed that
goat’s rue is a lactagogue. In Germany, Fragner[113] made a preparation
called Galegal, using galega as the active principle and combining it
with lactose to give it a pleasant taste and make it soluble in water,
milk, coffee, and tea. This preparation was reported on favorably
by Scherer,[114] who asserts that he obtained positive results in
fifty-four of the eighty cases in which he used it.
[112] Gillet-Damotti: Comp. rend. Acad. d. Sc., July 7, 1873.
[113] Fragner: Wien. med. Wchnschr. =60=:1033-1036, 1910.
[114] Scherer: Wien. med. Wchnschr. =60=:1033-1036, 1910.
More recently Huët[115] tested the effects of Theinhardt’s Hygiama
lactogene on four lactating women. This preparation is said to be
composed of hygiama,[116] galega and anise. Analysis showed that it
contains albumins, fat, soluble and insoluble carbohydrates, salts
and water. Huët could not observe any influence from the use of this
preparation, either on the quantity or on the composition of the milk
secreted.
[115] Huët: Nederlandsch Tijdschr. v. Geneesk. =1=:1353-1370, 1914.
[116] Hygiama is said to be a food consisting of condensed milk, with
(fatless) cocoa and cereals added to it (Encyclopedia and Dictionary of
Medicine and Surgery, 1907).
Nutrolactis[117] is a commercial preparation sold by the Nutrolactis
Company of New York at $1 a bottle. The label states that it contains
5 per cent. of alcohol; that it contains fluid extracts of the family
of “galactagogic plants,” and that it is intended to “increase the
supply of mother’s milk.” It is recommended to maintain “quality and
quantity until the end of normal lactation.” Nutrolactis is also
recommended for a mother debilitated by lactation. It is claimed that
“Nutrolactis does not _force_ the secretion of milk but merely assists
such secretion.” Years ago Millbank[118] reported good results from the
use of Nutrolactis. After more than a year’s use he concluded that it
was more satisfactory than any other lactagogue hitherto employed by
him, which is not saying very much, as specific lactagogues are as yet
unknown. Nutrolactis is still (1916) extensively advertised in various
medical journals as a lactagogue.
[117] The North Dakota Agricultural Experiment Station has recently
published (Bulletin 22, 1915, p. 386) a complete chemical analysis
of Nutrolactis. It contains only 0.60 per cent. solids (including
strychnin and emodin). It has a bitter taste. The alcohol content was
3.5 per cent. The report concludes: “a little strychnin, a little
alcohol, and a little laxative is about all there is to cause an
increase in the milk secretion.”
[118] Millbank: New York M. J. =50=:544, 1889.
METHODS OF INVESTIGATION
The alleged lactagogue action of galega and Nutrolactis was tested
on lactating dogs and goats. In these animals the psychic factors,
or suggestion, are largely eliminated. If the results had been
positive or had indicated lactagogue action, the test would have been
extended to nursing women. The puppies and kids were weighed before
and after nursing and a record kept of the amount of milk obtained at
each nursing (the animals nursing from three to five times daily).
The mothers were fed with varying doses of the drugs, and the milk
yield compared with that of a control period during which no drugs
were administered. An effort was made to keep the conditions of the
experiments uniform throughout.
The galega was ground and mixed with the food. The Nutrolactis was
mixed with food given by the stomach tube, or in some cases with a
spoon. Galega was tested on two goats and Nutrolactis on one goat and
nine dogs. The results are given herewith:
GALEGA
_Goat 1_: Control period, 1,600 gm., milk av. daily yield for 7 days.
Galega period (30 gm. galega mixed with oats), 860 gm., milk av.
daily yield for 8 days. Kids weaned at end of period.
_Goat 2_: Control period, 1,161 gm. milk av. daily yield for 9 days.
Galega period (30 gm. galega mixed with oats), 860 gm. milk av. daily
yield for 8 days. (25 gm. galega in same way), 810 gm. milk av. daily
yield for 10 days.
Control period, 896 gm. milk av. daily yield for 6 days.
NUTROLACTIS
_Goat 3_: Control period, 896 gm. milk av. daily yield for 6 days.
Nutrolactis period (30 c.c. Nutrolactis mixed with oats), 658 gm.
milk av. daily yield for 9 days.
Control period, 666 gm. milk av. daily yield for 5 days.
_Dog 1_: Control period, 176 gm. milk av. daily yield for 7 days.
Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 55 gm. milk
av. daily yield for 12 days.
_Dog 2_: Control period, 189 gm. milk av. daily yield for 6 days.
Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 72 gm. milk
av. daily yield for 11 days.
_Dog 3_: Control period, 93 gm. milk av. daily yield for 8 days.
Nutrolactis period (8 c.c. Nutrolactis on bread), 17 gm. milk av.
daily yield for 5 days.
_Dog 4_: Control period, 28 gm. milk av. daily yield for 7 days.
Nutrolactis period (8 c.c. Nutrolactis by stomach tube), 47 gm. milk
av. daily yield for 6 days.
(10 c.c. Nutrolactis by stomach tube), 43 gm. milk av. daily yield
for 8 days.
Control period, 41.5 gm. milk av. daily yield for 6 days.
Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 33.5 gm.
milk av. daily yield for 4 days.
_Dog 5_: Control period, 67 gm. milk av. daily yield for 6 days.
Nutrolactis period (10 c.c. Nutrolactis on bread), 81 gm. milk av.
daily yield for 6 days.
_Dog 6_: Control period, 40 gm. milk av. daily yield for 5 days.
Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 33 gm. milk
av. daily yield for 8 days.
Control period, 26 gm. milk av. daily yield for 4 days.
_Dog 7_: Control period, 283 gm. milk av. daily yield for 9 days.
Nutrolactis period (10 c.c. Nutrolactis by stomach tube), 155 gm.
milk av. daily yield for 15 days.
(15 c.c. Nutrolactis by stomach tube), 82 gm. milk av. daily yield
for 6 days.
Control period, 33 gm. milk av. daily yield for 3 days.
_Dog 8_: Control period, 238 gm. milk av. daily yield for 8 days.
Nutrolactis period (20 c.c. Nutrolactis on bread), 223 gm. milk av.
daily yield for 4 days.
(20 c.c. Nutrolactis on bread), 46 gm. milk av. daily yield for 6
days.
_Dog 9_: Control period, 223 gm. milk av. daily yield for 6 days.
Nutrolactis period (10 c.c. Nutrolactis on bread), 178 gm. milk av.
daily yield for 15 days.
(15 c.c. Nutrolactis on bread), 146 gm. milk av. daily yield for 5
days.
COMMENT AND CONCLUSION
Goat 1 had already been lactating for over two months, and the yield
was gradually decreasing at the time the observations were begun. The
administration of galega did not check this decrease. Goat 2 should
have been a very favorable subject, for the kid was about a week old
at the time the observations were begun. Both galega and Nutrolactis
caused a decrease in milk yield of this animal. This decrease is
perhaps partly due to the animal’s distaste for the drugs and her
consequent failure to eat as well as during the control periods.
Administration of Nutrolactis was accompanied by an increase in milk
in only two animals, Dog 4 and Dog 5. A detailed examination of the
records of these two dogs shows that in both cases _there was a
progressive increase in milk yield during the control period_ and that
administration of the drug failed to accelerate this increase. On the
contrary, the curve for Dog 5 takes a sudden drop immediately after the
first administration of the drug.
The records of Dogs 6 and 7 show that the yield during the second
control period is lower than that of the preceding periods. Although
the administration of the drug in both cases was followed by a decrease
in the yield, it may be urged that the drug has some lactagogue action,
for its discontinuance was followed by a decrease in yield. This
effect, however, is also apparent rather than real, for the data show a
gradual falling off in yield during the period of administration of the
drug, which decrease was not accelerated by withdrawing the drug.
Our data show that galega and Nutrolactis, when taken by mouth,
and the elements of suggestion excluded, had no beneficial effect
on lactation--at least in so far as the quantity of milk is
concerned.--(_From The Journal A. M. A., May 26, 1917._)
THE RUSSELL EMULSION AND THE RUSSELL PREPARED GREEN BONE
Report of the Council on Pharmacy and Chemistry
The following report on “The Russell Emulsion” and “The Russell
Prepared Green Bone,” marketed by the Standard Emulsion Company, was
submitted to the Council by a referee. The Council endorsed the report
and authorized its publication.
W. A. Puckner, Secretary.
The Russell Emulsion is put up in a neat package and advertised in an
attractive pamphlet, on the cover of which we are told: “Truth Always
Justifies The Superlative Degree.” As what follows in the booklet and
in the printed circulars certainly does not lack superlatives, this is
doubtless a warning.
In addition to the pamphlet and circular advertising, the product seems
to be systematically boomed by a lecture scheme in which one Dr. Hague
talks before medical societies and distributes advertising matter.
The lecture is succeeded by a follow-up letter scheme through which
matter is sent to members of the society. Hague ostensibly discusses
“lime starvation in tuberculosis,” but medical societies soon learned
to estimate his work as essentially to advertise the Russell products.
Last April the Medical Society of the State of Pennsylvania sent out
a circular letter to its county organizations on the subject of the
Russell-Hague propaganda which opens in this way:
“You have doubtless received a letter from Dr. William Grant Hague of
New York, offering to address your county society on Tuberculosis.
After due investigation, it is respectfully suggested that it may not
be desirable to ask him to address your society....”
The statements in the pamphlet and circular published are typical of
the whole method of exploitation. For example, can such claims as these
be surpassed by the veriest quack?
“SCIENCE cannot improve the means employed in producing THE RUSSELL
EMULSION.”
“GENIUS has not devised better methods than are used in
manufacturing THE RUSSELL EMULSION.”
“MONEY cannot buy better products than are used in THE RUSSELL
EMULSION.”
“EXPERIENCE cannot suggest a more nutritious combination of fats
than we use in THE RUSSELL EMULSION.”
The emulsion is said to be made of equal parts of beef-fat, coconut,
peanut and cottonseed oils, held in suspension by albumin. The latter
we are told is applied to each globule of the emulsion by an “elaborate
technical process” devised by Dr. Russell. The mixture is everywhere
spoken of as a “physiological” emulsion, but the word is always in
quotation marks. Why it is called “physiological” is not clear, but the
term may be counted on to impress the unthinking or the unscientific.
Numerous false and exaggerated statements are made about this
“physiological” emulsion with reference to food value. For instance:
“The nutritional value of fats differ; the nutritional value of
these fats and their increased efficiency by combination over all
others have been determined by extensive clinical observation.”
And also:
“The Russell Emulsion is approximated in food value by no other
emulsion or food product in existence.”
“A ‘physiological’ emulsion is a predigested food. It is absorbed
with little assistance from the digestive juices, and with no waste
of energy. It is, therefore, the ideal food....”
These are sample statements found in the pamphlet and accompanying
circular. A dozen or more pathologic conditions are mentioned in which
this “ideal food” is specifically indicated; but we find, also, this
curious statement: “Patients can rarely take this dose [speaking of the
maximum dose of 2 ounces night and morning] for more than three or four
weeks without showing symptoms of over-feeding.” This unguarded remark
about an ingestion of 48 grams of fat daily prompts one to ask what is
wrong with the “ideal predigested food.”
Russell is wedded to the idea that “lime starvation” is the main factor
in tuberculosis, and insists on the importance of large amounts of fat
for the “lime starved.”
“Dr. Russell was the original interpreter of the Lime Starved State
and originated The Lime Starvation Treatment in Tuberculosis. He
also first pointed out and emphasized the therapeutic importance of
regarding the combination of lime phosphate and casein, as brought
down by the rennet enzyme, as a chemical union.”
This overworked lime-starvation theory certainly lacks any tangible
confirmation (see in this connection a recent paper by Halverson,
Mohler and Bergeim, in The Journal, May 5, 1917), and to urge it
to promote the sale of a fat preparation is preposterous. On the
uninitiated the exaggerated pseudo-scientific language of the pamphlet
and circular advertisement will probably make some impression.
Unfortunately such things count not only with the layman who, having
no technical knowledge of physiology, cannot be expected to weigh the
evidence but also with those medical men who, while scientifically
educated, are influenced by unscientific claims when plausibly
presented. The pamphlet is a striking example of a style which is
dangerous because it smacks of science.
The Russell Company sells also a mixture called “Prepared Green Bone,”
said to be made by partially digesting ground chicken bones with
hydrochloric acid and pepsin and adding glycerin at the end of the
digestion. The product is a sticky, unappetizing looking mass, put up
in little earthenware boxes and advertised as a lime food, apparently
to go along with the fat emulsion. The greater value of a few glasses
of milk daily is evidently overlooked.
“The Russell Emulsion” and “The Prepared Green Bone” were declared
inadmissible to New and Nonofficial Remedies.
[Editorial Comment.--There are always those who are ready to exploit
the unfortunate tuberculous. It is, unfortunately, a fact that many
physicians accept as true, statements clothed with obscure and
voluminous quasi-scientific verbiage. Such men would laugh at the
bald claim that the moon is made of green cheese; when, however, one
plausibly and with due solemnity, affirms that the nocturnal luminous
earthly satellite is composed of an infinite aggregation of molecules
of bewildering and awe-compelling complexity, built up from the
recently discovered polypeptids, the whole being of a verdant tint, the
person addressed looks impressed and opines that it sounds reasonable!
The advertising for The Russell Emulsion and The Russell Prepared Green
Bone is dangerous because it appeals to the thoughtless--layman and
physician, alike.]--(_From The Journal A. M. A., June 23, 1917._)
BROM-I-PHOS
Report of the Council on Pharmacy and Chemistry
Brom-I-Phos (National Drug Company, Philadelphia) was submitted to the
Council with a label bearing the following statement:
“‘ALCOHOL 25 PER CENT.’
COMPOSITION--Per Fluidounce
Iodin 1 gr.
Bromin 1 gr.
Phosphorus 8-100 gr.
Aromatic Base q. s.”
A request for further information in regard to the composition of
Brom-I-Phos was sent to the National Drug Company. It was suggested
that since the preparation cannot contain the stated amounts of free
bromin, free iodin and free phosphorus, the form of combination in
which these elements are present should be set forth. In reply,
the firm said, first, that “Brom-I-Phos consists of Bromin, Iodin,
Phosphorus, Glycerin, Wine, Water and Volatile Oils. The Iodin is
rubbed up with a small percentage of Potassium Iodid and 95 per cent.
Alcohol, which solution is mixed with a solution of Bromine and
Spirits of Phosphorus which are combined with the base and aromatics.”
The manufacturer also admitted that phosphorus reacts with bromin
and iodin and that other reactions might occur, but maintained that
it was “justified in assuming the greater part, if not all of these
elements, are actually existent in the nascent state,” and asserted
that its “printed formula complies with our working formula in point of
quantities involved as well as existence of elements in an uncombined
state.”
The A. M. A. Chemical Laboratory reported, on the contrary, that
no free phosphorus, free bromin or free iodin could be found in
Brom-I-Phos, and that no bromate or iodate could be found; bromid and
iodid were present. The addition of silver nitrate to an acidulated
portion, diluted with water, gave an amount of silver halid roughly
agreeing with that which would be obtained had the claimed amount of
bromin and iodin (together with some potassium iodid) been used in the
preparation of Brom-I-Phos and in the process of manufacture become
converted to bromid and iodid.
The Council declared Brom-I-Phos inadmissible to New and Nonofficial
Remedies, for conflict with Rules 1, 4, 6, 8 and 10.
The statement of composition is unsatisfactory and misleading in that
it suggests that the preparation contains bromin, iodin and phosphorus
in the free (elementary) state. The presence of the potent elementary
phosphorus is especially suggested by the small amounts of “phosphorus”
declared.
The following statement on the label of the trade package constitutes
an indirect advertisement to the public:
“INDICATIONS: Scrofula, Coryza, Hay Fever Necrosis, Bronchial and
Throat Affections, Catarrhal Pneumonia, Glandular enlargements of
the Spleen, Thyroid, and Lymphatics, Rickets and Syphilis.”
The following claims are therapeutic exaggerations:
“The Ideal Alterative”
“... indicated in all cases where an alterative is desired ...”
“The association of Bromin with Iodin in Brom-I-Phos materially
enhances the product in the treatment of chronic affections of
the skin, depraved conditions of the mucous membranes, tertiary
syphilis, glandular enlargements, etc.”
In that it suggests that the phosphorus in Brom-I-Phos is more readily
assimilated than ordinary phosphate, the following is misleading:
“The Phosphorus contained in Brom-I-Phos is readily assimilated and
at once acts as a nutrient to the nervous and osseous structures of
the body, stimulates metabolism and increases mental activity.”
The recommendation: “Your specification of Brom-I-Phos in the
treatment of Syphilitic cases will immediately prove beneficial to the
patient” is not supported by evidence. The name does not indicate that
Brom-I-Phos is an alcoholic preparation with iodid as its essential
constituent, but suggests that phosphorus is an important constituent,
whereas the amount of phosphate or phosphite, produced by the action
of iodin on elementary phosphorus (if the amount of phosphorus used in
making the preparation is correctly stated) is insignificant.
The combination of bromin, iodin and phosphorus, or bromid, iodid and
phosphate, is irrational because these elements are not of mutual
assistance to each other in the conditions for which Brom-I-Phos is
advertised.
The Council’s report was submitted to the manufacturer of Brom-I-Phos
for comment; the reply contained nothing to permit a revision of the
previous conclusions.
The Council declared Brom-I-Phos inadmissible to New and Nonofficial
Remedies.--(_From The Journal A. M. A., June 30, 1917._)
CREOSOTE-DELSON AND CREOFOS
Report of the Council on Pharmacy and Chemistry
Creosote-Delson and Creofos, or Creosote with Hypophosphites,
were submitted by the Delson Chemical Co., Inc., New York City.
Creosote-Delson is said to be “beechwood creosote from which
the irritating and caustic properties are removed by fractional
distillation.” It is claimed that Creofos contains “2 grains of
Creosote-Delson and 3-3/5 grains of the combined Hypophosphites in each
fluidrachm of the mixture or emulsion, the lime salt predominating.”
It is also claimed that “the primary object of the hypophosphites in
this preparation is that of maintaining the refined creosote in a
pure, unoxidized state, and that no particular claim for therapeutic
action on their part is advanced.” It is explained further, however,
“the addition of the lime was prompted by the belief ... that the
fundamental cause of pulmonary tuberculosis is lime starvation....”
The assertions are made that Creosote-Delson is superior to the
official creosote because it can be taken “abundantly and persistently
without harm to or interference with stomach and kidneys” and can
be “taken uninterruptedly and indefinitely,” while the dosage
is “unlimited by any former knowledge of Creosote Therapy.”
Creosote-Delson is not on the market except in the combination Creofos,
although it is supplied on request.
Creofos is advised in the treatment of tuberculosis, whooping cough,
measles, “Grippe and Colds,” bronchitis, asthma, “Intestinal Affections
(Colitis, Summer Diarrhoea, etc.),” while its use is suggested for the
“prevention of the spread of contagious diseases,” and for “preventing
contagion in minor contagious diseases at any rate, in schools and
families.”
The following advertisement has recently appeared in the _New York
Medical Journal_ and in the _Therapeutic Gazette_:
CREOFOS MEDICATION
is the successful development of the most advanced practice in
the treatment of infectious diseases. It destroys completely the
causative organisms by a bactericide many times more powerful than
phenol, yet absolutely harmless to animal life.
Unlike serums, its activity is not confined to any specific
disease, and its use insures against sequelae (as pneumonia
following grippe).
Especially valuable in the treatment of infants and patients of
delicate constitution and in cases where time is of importance.
The Delson Chemical Co. was requested to supply information regarding
the identity of Creosote-Delson and to support the claim that although
it is “the whole drug” its dosage is “unlimited by any former knowledge
of Creosote Therapy.” The reply was virtually an admission that the
toxic, caustic, phenolic components of creosote were present in
Creosote-Delson just as in the official creosote.
The referee of the Committee on Therapeutics in submitting his report
to the Council pointed out that it is difficult to discuss the
pharmacologic merits of a semisecret preparation, like Creosote-Delson,
claimed to be more acceptable to the human organism than the official
product it is intended to supplant, when the action of the parent drug
is still questioned or disputed by eminent clinicians.
Absorption experiments have been carried out with creosote and creosote
compounds, such as creosote with hypophosphites or calcium or creosote
carbonate, chiefly by a study of the elimination products in the urine.
But any evidence so far offered that these combinations increase
absorption and lessen the irritating, caustic or toxic properties has
been wholly inconclusive. The evidence offered by the Delson Chemical
Co. presented no control experiments with the official creosote and did
not prove that either Creosote-Delson or Creofos was less toxic than a
corresponding amount of ordinary beechwood creosote.
The referee concluded that no proof had been offered that these
preparations are materially superior to ordinary creosote preparations
from the pharmacologic or therapeutic standpoint, and that the claims
made for Creosote-Delson and Creofos are unwarranted in the light of
our knowledge of the properties of creosote. The advertisement quoted
above is an example of unproved and unwarranted claims.
On the recommendation of the referee, the Council declared
Creosote-Delson and Creofos inadmissible to New and Nonofficial
Remedies, for conflict with the rules as follows:
_Creosote-Delson_: The information so far available is not sufficient
to define the nature, or composition, of Creosote-Delson, or to
indicate in how far this product differs, if at all, from the
official creosote (conflict with Rule 1). No methods are furnished
for determining the identity or composition of Creosote-Delson
(conflict with Rule 2). The available information does not show that
Creosote-Delson has advantages over creosote (conflict with Rule 6).
_Creofos_: The composition of Creosote-Delson not having been
furnished, the statement concerning the composition of Creofos is
also unsatisfactory (conflict with Rule 1). The therapeutic claims
are unsubstantiated and grossly exaggerated (conflict with Rule 6).
The name is not descriptive of its composition as is required for
pharmaceutical mixtures (conflict with Rule 8). There is no evidence
that hypophosphites prevent decomposition of creosote (if this
occurs). Hence the inclusion of hypophosphites must be considered
irrational (conflict with Rule 10).
The Council’s report was sent to the Delson Chemical Co. for
consideration. The firm’s reply contained nothing to warrant a revision
of the report, and the Council voted that Creosote-Delson and Creofos
were inadmissible to New and Nonofficial Remedies and authorized the
publication of this report.--(_From The Journal A. M. A., July 7,
1917._)
TRINER’S AMERICAN ELIXIR OF BITTER WINE
Report of the Council on Pharmacy and Chemistry
Triner’s American Elixir of Bitter Wine is a wine to which bitter drugs
and laxatives have been added. Though evidently intended for public
consumption, it is also advertised to physicians, and consequently the
Council publishes this report.
Some recent advertisements read:
“It Acts Well and Is Very Palatable. These are the reasons why so
many physicians recommend TRINER’S AMERICAN ELIXIR OF BITTER WINE.
Free from any chemicals. Prepared from bitter herbs roots and barks
of eminent medicinal value and pure natural red wine. A safe relief
in auto-intoxication, constipation, weakness, etc. Price $1.00. At
drug Stores. Samples gratis upon request only to physicians.”
“A Laxative Tonic. In cases of constipation and its sequelæ,
autointoxication, weakness and nervousness you should try _Triner’s
American Elixir of Bitter Wine_. This preparation consists of
Cascara Sagrada, Dandelion, Gentian Root, with Licorice in Pure Red
Wine as a base, with Aromatics.”
Triner’s American Elixir of Bitter Wine is put up in bottles said to
hold 1 pint, 5-1/3 fluidounces. The label declares the presence of from
16 to 18 per cent. alcohol by volume, and states that “no special tax
is required by the laws of the U. S. for the sale of this medicinal
preparation.” The circular contains the following recommendations for
its use:
“... It should be used in all cases calling for a safe evacuation
of the bowels, without weakening the body or causing any pain or
other discomfort; in loss of appetite, nervousness and weakness.”
“Triner’s American Elixir of Bitter Wine consists of two principal
ingredients, viz., Red Wine and Medicinal Herbs.”
“Red Wine strengthens the intestines and regulates their work. It
also increases the appetite, stimulates and strengthens the body.”
“Use Triner’s American Elixir of Bitter Wine always when a thorough
cleaning out of the intestines is needed. Arrange the dose to suit
your condition and habits.”
“In Chronic Constipation the dose of Triner’s American Elixir of
Bitter Wine should be increased or taken oftener.”
“Many Female Troubles are caused or aggravated by constipation and
ladies should always pay good attention to this fact.”
In addition to Triner’s Elixir of Bitter Wine, the circular--in
English, Polish, Russian, Spanish and other languages--advises the
use of Triner’s Angelica Bitter Tonic, Triner’s Red Pills, Triner’s
Liniment and Triner’s Cough Sedative.
The composition of this “wine”--some bitter drugs, a laxative and a
tannin-containing, constipating red wine--and advertising propaganda
all tend to the continued use of this alcoholic stimulant and thus to
the unconscious formation of a desire for alcoholic stimulation. As
the medical journal advertisements may lead physicians to prescribe
this secret and irrational preparation and thus unconsciously lead to
alcoholism, the Council authorized publication of this report.--(_From
The Journal A. M. A., July 14, 1917._)
TRIMETHOL
Report of the Council on Pharmacy and Chemistry
Trimethol is the trade name for a substance said to be
trimethyl-methoxy-phenol of the formula C₆H(CH₃)₃(OCH₃).OH--1:2:4:5:6,
originated by J. T. Ainslie Walker. It is sold as a nontoxic germicide,
having a Rideal-Walker phenol-coefficient of 40, even in the intestinal
canal. It is described as insoluble in water and not to be decomposed
in the alimentary tract, and to be excreted unchanged in the feces.
Trimethol itself is not obtainable. Pharmaceutical
preparations--Trimethol Syrup, Trimethol Capsules and Trimethol
Tablets, said to contain Trimethol--are prepared by The Walker-Leeming
Laboratories and sold by Thos. Leeming and Co., New York.
Trimethol preparations are advertised for use in all conditions
dependent on intestinal putrefaction. The advertising claims made are
very extensive and some of them give to “Trimethol” the scope of a
panacea. For example:
“Physicians are constantly reporting cases where Trimethol has been
especially efficient, and describing conditions (until recently not
associated with intestinal infection) which have been distinctly
benefited by its use. This would seem to bear out the contentions
of Charcot and Metchnikoff that 90% of all human ailments have
their origin in intestinal infection.
“The careful practitioner, when in doubt, will bear this in mind,
now that we have a really efficient and non-toxic intestinal
germicide--not a mere antiseptic.”
The Walker-Leeming Laboratories have not formally requested the Council
to consider the Trimethol preparations, though in a personal letter to
a member of the Council J. T. Ainslie Walker invited an investigation
of his compound.
For the investigation of Trimethol and its preparation the Council
secured the aid of a bacteriologist who has given much attention to
the study of the intestinal flora. The Walker-Leeming Laboratories and
J. T. Ainslie Walker were both asked to submit details of experimental
studies and also to furnish a supply of the pure “Trimethol.” But the
only data sent that had any definiteness set forth the bacterial counts
made of plate cultures of stools of one patient before and after the
administration of Trimethol Capsules.
REFUSE TO FURNISH TRIMETHOL
The request for the pure substance was refused, on the grounds that the
substance was not used in the undiluted form. The failure to furnish
the chemical substance claimed as the essential constituent of the
Trimethol preparations is to be deprecated if indeed it has not greater
significance. At least it made it impossible for the Council’s expert
to express his results in terms of absolute Trimethol of established
composition. The data obtained apply only to the market preparations
claimed to contain Trimethol. So far as the investigation and report
go, “Trimethol” is a hypothetical substance.
Clinical or animal tests of the asserted intestinal antiseptics have
hitherto given equivocal results because it is impossible, on the
one hand, to predict the course of any intestinal infection, or,
on the other hand, to determine what effect, if any, was produced
by administration of the medicament. It therefore seemed unwise to
undertake this line of investigation until the more direct laboratory
bacteriologic methods had been exhausted. Consequently the investigator
checked, in the first place, the phenol coefficient of one of the
Trimethol preparations and then also determined its “penetrability”
coefficient. Although by both methods Trimethol was found to be a
germicide, the results did not indicate any remarkable potency or other
properties suggesting that the drug possessed special therapeutic
value. From the results obtained it appeared inadvisable to proceed
further with the work until more definite evidence of the nature and
of the value of the substance should be at hand. The report of the
bacteriologic investigation follows:
THE BACTERIOLOGIST’S REPORT
“I have made no attempt to study the effects of internal administration
of Trimethol on the intestinal flora. The methods available at the
present time of enumerating the numbers of _viable_ bacteria in
the feces are probably not accurate within 100 per cent. and the
precision of such determinations is equally variable. The physiologic
factors involved are so complex that they would appear to make a
really valuable assay a question of many months’ careful study. If
it were possible to administer known amounts of Trimethol, as such,
the problem might be worth while; inasmuch as the available reactive
substance is not at present quantitatively assayable, this phase of the
investigation barely seems practicable.
“‘Trimethol Syrup,’ as such, appears to be about 10 per cent. as
efficient in its germicidal value as carbolic acid. If the assay,
3/4 m. Trimethol per drm. (as the label indicates), is correct, the
substance would appear to possess germicidal merit provided enough
could be administered, if it is not influenced by passage through the
stomach.
“A package containing four four-ounce bottles labeled ‘Trimethol, A
Non-Toxic Germicide SYRUP Representing 3/4 m. Trimethol per drm.,
Alcohol 1-1/2 per cent.’ was received at the laboratory Dec. 15,
1916. Later a smaller package containing, according to the label, 100
Trimethol tablets, each 5 gr., representing 1-1/4 m. Trimethol, was
received. The tablets were apparently chocolate coated.
“Two separate series of tests were made upon the syrup. (_a_) PHENOL
COEFFICIENT, using the method outlined in _Bulletin No. 82_, Hygienic
Laboratory, Method of Standardizing Disinfectants With and Without
Organic Matter. (_b_) A PENETRABILITY COEFFICIENT by the method of
Kendall and Edwards, _Journal of Infectious Diseases_, 8, 250.
“The former method compares the viability of naked germs in a 1 per
cent. carbolic acid solution as a standard, with various dilutions
of the germicide to be tested. The latter measures the relative
diffusibility and germicidal power of carbolic acid and various
dilutions of the germicide to be tested upon _Bacillus coli_ suspended
in 1.2 per cent. agar which is molded in cylinders of one centimeter
diameter after infection with the organism.
“The first method--phenol coefficient--possesses advantages and
disadvantages which are well known and need no mention here. It is
worthy of notice, however, that as the death rate of the bacteria
increases during the progress of the test, it becomes increasingly
difficult to maintain a uniform suspension of living organisms so
that each loopful removed shall exactly represent the developmental
potentiality of the residual organisms.
“The second method theoretically covers the possibility because all the
organisms are immobilized and are exposed to the germicide in direct
proportion to its diffusibility until the center of the agar mass is
reached, where the residual viable bacteria are presumably located.
Inasmuch as the penetrability of an intestinal mass is involved in a
discussion of intestinal germicides, the propriety of utilizing this
‘penetrability coefficient’ in this connection is obvious, in spite of
its patent shortcomings.
“It is unnecessary to discuss the technique--the standard broth
mentioned in the Hygienic Bulletin, a temperature of 70 F., a standard
4 mm. loop and careful attention to dilutions (using distilled water)
were all observed. The various dilutions of Trimethol Syrup were made
with accurate volumetric pipettes, measuring flasks and distilled water
was used as a diluent.
“The results of several determinations, using Trimethol Syrup from
three separate bottles, were in sufficient accord to warrant the
statement that a dilution of 1/10 of Trimethol Syrup was equivalent
to a 1/100 dilution of carbolic acid, using _Bacillus typhosus_ as
the test organism. Both solutions--the Trimethol and phenol--killed
the organism in the interval between 7-1/2 minutes and 10 minutes’
exposure. That is to say, our observations indicate that under
standard conditions as defined above, a 10 per cent. solution of
Trimethol Syrup is equivalent in germicidal powers, as defined by the
phenol coefficient to a 1 per cent. solution of phenol. Naturally, no
predictions can be drawn from these observations indicative of the
value as an intestinal germicide of Trimethol itself.
“The PENETRABILITY COEFFICIENT resulted as follows: A 5 per cent.
solution of phenol killed _Bacillus coli_, suspended uniformly
throughout a cylinder of 1.2 per cent. agar in the interval between
60 and 90 minutes. A 1 per cent. solution of phenol killed the same
organisms under the same conditions in the interval between two and
one half and three hours. An undiluted solution of Trimethol Syrup
killed the organisms in the interval between two and one half and three
hours. A 10 per cent. solution (nine volumes of distilled water to one
volume of Trimethol Syrup) failed to kill the organisms in four hours.
It would appear that undiluted Trimethol Syrup has the same combined
penetrability and germicidal value as a 1 per cent. phenol solution.
“The PHENOL COEFFICIENT: A 10 per cent. solution of Trimethol Syrup
in distilled water (nine volumes of distilled water to one volume of
Trimethol Syrup) possesses the same germicidal power as a 1 per cent.
solution of carbolic acid. This coefficient takes no cognizance of the
_actual amount of Trimethol as such_--it merely indicates the relative
germicidal power of the Trimethol Syrup as sold.”
The preceding report shows that Trimethol Syrup has a phenol
coefficient of 1/10, and, assuming Trimethol Syrup contains the amount
of Trimethol declared, the substance Trimethol would have a phenol
coefficient of 8-1/3 instead of 40, as is claimed. According to Kendall
and Edwards’ method, the penetrability-germicidal value of the syrup is
equal to a 1 per cent. solution of phenol.
WALKER’S REPLY TO CRITICISM
The report of the bacteriologist was submitted to The Walker-Leeming
Laboratories for comment. The following reply was received from J. T.
Ainslie Walker:
(_May 22, 1917_) “In reply to your letter of the 15th inst., which
has just been placed before me on my return to town, I have to
inform you that the potent constituent of Trimethol Tablets and
Trimethol Syrup is not fully available as a bactericide until it
comes in contact with the pancreatic fluid.
“As you will see from the enclosed extracts from clinical reports,
the therapeutic value of Trimethol has been well established.
“As regards penetrability, no claim has ever been made for
Trimethol in this connection; and, as I pointed out in my original
paper (_American Medicine_, September, 1914), when referring to the
independent tests made by Dr. Frederick Sondern, ‘No attempt was
made to determine the bacterial content of the solid particles,
as in the opinion of the writer sterilization of the interior of
these particles is not only absolutely impossible, but wholly
unnecessary. The fact of the fluid contents of the canal being
sterile may be taken to indicate that the exterior of all solid
particles is in a like condition, and therefore harmless. It is
the organisms in the fluid portions only that produce the deadly
effects through the chemical substances they secrete; those in
the interior of the solid portions (_i. e._, as evacuated) may be
disregarded, as they are not available for good or evil.’
“I must confess to no little surprise on learning that your
investigator is still using the Hygienic Laboratory method of
determining phenol coefficients. I would respectfully suggest that
you call his attention to the critical comparison of the Hygienic
Laboratory and R.-W. Tests, which he will find in the enclosed
reprint from the _New York Medical Journal_ of March 11, 1916:
‘Instead of being an improvement upon the standard R.-W. Test,
the so-called Hygienic Laboratory Method is so defective as to
be wholly unreliable, and incapable of furnishing results of any
scientific or practical value whatever.’”
As to the statement that the potent constituent of Trimethol Tablets
and Trimethol Syrup is not fully available as a bactericide until it
comes in contact with the pancreatic fluid, attention is called to a
leaflet, which accompanies each bottle of Trimethol Syrup, that reads:
“Trimethol is insoluble in water, but when properly emulsified has
a Rideal-Walker co-efficient of 40; that is to say, it is 40 times
more efficient as a germicide than phenol (pure carbolic acid).”
The Trimethol Syrup which was used in the investigation, when mixed
with water produced an almost perfectly transparent solution, which
justifies the assumption that the proper physical conditions were
observed and that this objection is not well founded.
As regards the relation of pancreatic fluid to bactericidal
availability of Trimethol, there is little to say, other than that the
published statements in the advertising accompanying the packages make
no mention of this point. It would be interesting to know what, if any,
relation the pancreatic fluid has to this substance, in view of the
statement that it “has a Rideal-Walker coefficient of 40.”
The Trimethol “literature” does not throw light on the question, What
is the germicidal value of Trimethol Syrup as compared with phenol?
The only available method of determining the germicidal value of a
liquid disinfectant is to make a direct comparison of the substance
in question with phenol under similar conditions. Given parallel
conditions, not obviously prejudicial to the substance tested in
contrast to the standard solution, the results are comparable, and
furnish a basis for estimating the relative germicidal power of the two
substances. In the investigation, Trimethol Syrup and phenol were thus
compared.
As regards the contention that the bacteria within fecal masses are
harmless, this may be granted. But it must also be admitted that
these intestinal masses are constantly being reformed so that buried
micro-organisms do not remain in the interior. For this reason, the
determination of the penetrability coefficient of a germicide is
pertinent.
Regarding the respective merits of the old Rideal-Walker and the
newer U. S. Hygienic Laboratory method of determining the phenol
coefficient, the Rideal-Walker method was found to possess certain
drawbacks, and in an attempt to overcome these the “_Lancet_ Method”
was evolved; this method in turn was improved in the U. S. Hygienic
Laboratory and led to the United States Public Health Service Hygienic
Laboratory method for the determination of the phenol coefficient of
disinfectants (published in _Hygienic Laboratory Bulletin 82_). In
1913 this method was formally adopted by the Council for the valuation
of disinfectants or germicides of the phenol type, and the method is
now in general use for this purpose in the United States.[119] In this
connection Hiss and Zinsser may be quoted (Ed. 2, page 80): “The most
precise method of standardizing disinfectants is that now in use in the
United States Public Health Service.” Stitt, director of the United
States Naval Medical Schools, in his Practical Bacteriology, Blood
Work and Parasitology (Ed. 4, page 473) says: “In the United States
disinfectants are rated according to the Hygienic Laboratory Phenol
Coefficient.”
[119] Those who are interested in the relative merits of the
Rideal-Walker, the _Lancet_ and the Hygienic Laboratory methods for
the valuation of disinfectants, should read the following: Method
of Standardizing Disinfectants with and without Organic Matter,
J. A. M. A., Aug. 24, 1912, p. 667; Standardization of disinfectants,
Report of the Council on Pharmacy and Chemistry, J. A. M. A., April
26, 1913, p. 1316; Standardizing Disinfectants, J. A. M. A., Sept. 30,
1916, p. 883.
The Council adopted the recommendation of the Committee on Pharmacology
to the effect that the claims made for Trimethol are unsupported by
acceptable evidence. Accordingly, Trimethol and the pharmaceutical
preparations said to contain it--Trimethol Syrup, Trimethol Capsules,
and Trimethol Tablets--were held ineligible for New and Nonofficial
Remedies.--(_From The Journal A. M. A., Aug. 11, 1917._)
FERRIVINE, INTRAMINE AND COLLOSOL IODINE
Report of the Council on Pharmacy and Chemistry
E. Fougera & Co., Inc., New York, acting as agent for The British Drug
Houses, Ltd., London, advertise “Ferrivine,” “Intramine” and “Collosol
Iodine” to the medical profession. A circular entitled “Ferrivine, The
New Anti-Syphilitic Remedy” begins:
“FERRIVINE is the name given to ferric tri-para-amino-benzene
sulphonate. This iron compound was first prepared by Mr. J. E. R.
McDonagh, F. R. C. S., by whom it has been both biologically and
clinically tested. It is slightly soluble in water, the solution
having an acid reaction.
“INDICATIONS
“According to Mr. J. E. R. McDonagh’s researches, the phases of
the _Leucocytozoon syphilids_ are killed by the lipoid-globulin
molecules of the serum, which possess a stereochemical molecular
configuration homologous to those of the lipoid-globulin
molecules of the parasite. The process is one of absorption, a
chemico-physical reaction which is in part dependent upon the
supply of active oxygen. Active oxygen is formed directly by
oxidation processes and the peroxide necessary for its formation
directly by reducing processes. Oxidation is increased by metals
and reduction by non-metals. The non-metal which acts in the body
as the normal reducing agent is sulphur, hence the discovery of
Intramine (see separate pamphlet). The metal which acts in the body
as the normal oxidising agent, is iron, hence the discovery of
Ferrivine.”
A circular, “Intramine, a New Non-Toxic Compound for the Treatment of
Protozoal and Chronic Bacterial Diseases,” expounds Mr. McDonagh’s
ideas of the treatment of syphilis with Ferrivine and Intramine by
means of the oxidising action of Ferrivine and the reducing action of
Intramine and asserts:
“As the ultimate administration of oxidising and reducing agents
will benefit almost any infection, it may be said that Intramine is
indicated in all protozoal diseases, and in all chronic bacterial
diseases, especially in tuberculosis, presumably in leprosy and
possibly in malignant disease [cancer?]. To the administration of
Intramine there are no contraindications.”
We are also told that:
“Intramine is useful injected into the urethra.... In cases of
chronic urethritis and perifolliculitis ... invaluable as a local
application to chronic ulcers ...”
The Intramine circular includes a “Scheme of Treatment for Syphilis”
which advises, in addition to Intramine, Ferrivine or salvarsan,
mercury and iodids, the use of another proprietary called “Collosol
Iodine.” An inquiry addressed to Fougera & Co. in regard to the
character and composition of this preparation, brought the reply that
the firm had no knowledge of its identity.
This “scheme of treatment” is objectionable in that it advises the
“stock” treatment of a disease which demands individualization and
further in that whatever beneficial effects may result from the use
of mercury and iodid is likely to be ascribed to the preparations
“Intramine,” “Ferrivine” and “Collosol Iodine.”
The advertising for Ferrivine and Intramine sent out by Fougera & Co.
contains no experimental or clinical data on which an estimate of their
value may be based. Apparently in England, where these products were
originated, little has been published regarding them.
There is, however, one report which may be accepted as a carefully
controlled clinical trial. In the _Lancet_ (June 17, 1916, p. 1214)
L. W. Harrison, D.S.O., M.B., Ch.B.Glasg., and C. H. Mills, M.R.C.S.,
L.R.C.P.Lond., report on “The Effect of Ferrivine and Intramine on
Syphilis.” After briefly reviewing the theories which form the basis
of McDonagh’s proposed treatment of syphilis with his discoveries
“Ferrivine” and “Intramine” the authors point out:
“... that Mr. McDonagh’s biological discoveries ... have not been
publicly confirmed by any biologist of standing ...”
While:
“... eminent chemists have confessed themselves unable to
understand his chemistry.”
The authors explain:
“Recognizing that this might prejudice our practical tests of
Intramine and Ferrivine, we have taken particular care to guard
against their influence, cross-checking our observations and
submitting them to others for confirmation or otherwise.”
Harrison and Mills chose for a test three ordinary cases of secondary
syphilis, cases with well marked lesions, the clinical progress of
which could easily be watched and from which it was easy to obtain
specimens for microscopic examination. After a detailed account of
the three cases--which records grave conditions resulting from the
treatment and which shows the inefficiency of the drugs--they write:
“From the above account it will be seen that the local and general
reactions which follow the injection of these preparations are
by no means pleasant. In the case of Intramine the pain is
undiluted torture and lasts so for two or three days. One of us had
previously treated four cases with Intramine and the same local
reaction occurred in these. In two of them abscesses have burst
outwardly, one of which is still discharging necrotic débris, ten
weeks after the injection, and will take many more weeks to close.
In those cases where no abscess has yet burst it is easy to feel
by the gap in the muscles that considerable necrosis has occurred.
None of these effects can be ascribed to sepsis, as most rigid
aseptic precautions were taken. Further, particular care was taken
to make the injections strictly intramuscular. The constitutional
symptoms which follow immediately upon the injection of Ferrivine
are distinctly alarming, and such as would cause one to hesitate
before injecting this remedy into any but robust patients.”
Harrison and Mills estimate the therapeutic effects of these drugs thus:
“1. That Ferrivine entirely failed to cause _S. pallida_ to
disappear from the lesions of three well-marked cases of secondary
syphilis.
“2. After the failure of Ferrivine to cause the disappearance of
_Spirochaeta pallida_ from a mucous patch a single dose of 0.3 gm.
salvarsan effected this in 18 hours, and the patch, which had
hitherto been uninfluenced, had healed within 48 hours.
“3. Clinically we were unable to detect any influence of either
or both these compounds on syphilitic lesions, although each of
them was of the variety which heals in a week or ten days under
salvarsan treatment.
“4. Further syphilitic lesions appeared immediately after the
treatment in one of the two cases treated with both Ferrivine and
Intramine. A mucous patch appeared on one tonsil as well as further
syphilitic papules from which spirochetes were obtained. The other
case developed nephritis, with albumin and epithelial casts; which
was not present prior to the injections.”
While from these cases the obvious conclusion was drawn that Intramine
and Ferrivine “have no specific effect on early syphilis,” these
authors subsequently treated a case of tertiary syphilis with the
drugs. An Intramine injection caused pain for several days but did
not stop the progress of the disease. Ferrivine was then administered
“not without a feeling of grave responsibility” in view of their
previous experiences. They state that “the reaction which resulted
in this instance was the most severe” they ever experienced after
an intravenous injection of any of the antisyphilitic remedies with
which they had previously worked. It is stated that “for a period
of some minutes there was grave doubt as to the patient’s survival.”
After resuscitation the patient passed a disturbed night, and rigors
which ensued lasted until the following afternoon. The author’s report
that in this case also no clinical improvement occurred and that the
Intramine-Ferrivine treatment was replaced by a course consisting of
salvarsan, potassium iodid and mercurial inunction.
Ferrivine, Intramine and Collosol Iodine were declared inadmissible to
New and Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 8,
1917._)
ESKAY’S NEURO PHOSPHATES
Report of the Council on Pharmacy and Chemistry
For the information of the profession the Council has prepared and
authorized for publication the following report on Eskay’s Neuro
Phosphates.
W. A. Puckner, Secretary.
Eskay’s Neuro Phosphates (Smith, Kline & French Co., Philadelphia) is
offered to physicians under the claims that it contains alcohol, 17 per
cent., and sodium glycerophosphate, 2 grains, calcium glycerophosphate,
2 grains, and strychnin glycerophosphate, 1/64 grain, in each
dessertspoonful. It is called a “Nerve Tissue Reconstructive,” and its
advertising claims are based on the discredited theories that certain
disorders are due to a deficiency of phosphorus in the nerve structure
of the body, and that glycerophosphates are assimilated more readily
than ordinary phosphates. This assumption was based on the knowledge
that the lecithins, which form a part of the nerve structure, contained
the glycerophosphate radical in the molecule. In line with this, Smith,
Kline & French Co. aver:
“Eskay’s Neuro Phosphates is of marked value in many acute and
chronic conditions, in nervous exhaustion following mental and
physical strain, neurasthenia, paralysis, anemia, tuberculosis,
marasmus, debility and wasting diseases generally, and the
nerve-weakness of the aged. It is particularly useful in
convalescence from acute diseases and in the nervous condition
following la grippe.”
In its report on “The Therapeutic Value of the Glycerophosphates” (The
Journal, Sept. 30, 1916, p. 1033) the Council pointed out that the
therapeutic use of the glycerophosphates was based on the assumption
that the inorganic phosphates cannot supply the body’s needs of
phosphorus or that the use of organic compounds “spared” the system
the necessity of making such synthesis. The report presented evidence
to show that the glycerophosphates are not absorbed as such, but
that they are split into inorganic phosphates before absorption. The
Council showed that there was convincing evidence that the animal
organism synthesizes its complex organic phosphorus constituents from
inorganic phosphates, and that organic phosphorus is of no more value
as a food than inorganic. Despite this the Neuro Phosphates advertising
makes use of the fallacious assumption regarding the action of the
glycerophosphates.
Pleading for the particular mixture represented by the proprietary, it
is asserted that:
“Sodium glycerophosphate is of special value in neurasthenia,
Addison’s disease, phosphaturia and phthisis.”
and that calcium glycerophosphate “is employed in bone fracture,
rachitis, tuberculosis and various wasting diseases.”
The phosphorus content of 1/64 grain of strychnin glycerophosphate is
ridiculously small. Yet it is asserted that this strychnin salt is of
superior value because it combines the effects of strychnin with a
“food-like form of phosphorus.” Eskay’s Neuro Phosphates has an acid
reaction which is capitalized, thus:
“Experiments have shown that the acid glycerophosphates are more
rapidly absorbed and are more efficient than the neutral salts.”
And as a further illustration of extravagant claims:
“As a glycerophosphoric acid in the form of lecithin is
normally present in spermatozoids, it is but natural that the
glycerophosphates should exhibit aphrodisiac effects (as has been
observed), but this result does not seem to obtain in all cases.”
Is this a clumsy attempt to exploit this “nerve phosphate” as a “lost
manhood” cure?
The Council held Eskay’s Neuro Phosphates ineligible for New and
Nonofficial Remedies because unwarranted therapeutic claims are made
for it and because the administration of strychnin, calcium, phosphate
and alcohol is not conducive to rational therapeutics, particularly
when such a mixture is marketed under a name which indicates but one of
its constituents.--(_From The Journal A. M. A., Sept. 29, 1917._)
K-Y LUBRICATING JELLY
Report of the Council on Pharmacy and Chemistry
Because of inquiries received, the Council has authorized publication
of the following report declaring K-Y Lubricating Jelly inadmissible to
New and Nonofficial Remedies.
W. A. Puckner, Secretary.
K-Y Lubricating Jelly (Van Horn and Sawtell, New York), originally
advertised as a lubricant for instruments and the hands, is now also
recommended as a therapeutic agent. If the claims for “K-Y” were
limited strictly to such effects as result from the purely mechanical
properties of a lubricant, it might be held that it would not come
under the purview of the Council. The preparation, however, while
introduced as a lubricant, is now offered for a broader field of use,
and the manufacturers make claims which are not supported by any
evidence available to the Council. Evidence the following, taken from a
circular that accompanies the package:
“K-Y allays smarting and burning at once through its pronounced
soothing and cooling effects, and thus makes an admirable dressing
for burns.”
“Many physicians make a practice of anointing the bodies of their
measle and scarlet fever patients with ‘K-Y,’ in this way affording
gratifying relief from itching and irritation, and effectively
preventing dissemination of infectious material.”
And this from another circular:
“I had one of the most troublesome cases of pruritus vulvæ that I
had ever seen. I guess I must have tried everything and the case
had been referred to me by another man, who had previously tried
everything, including cauterization. Well, one day I was examining
her, and of course K-Y on the speculum--the irritation seemed to
quiet down, and the following day she said she felt no effects from
it at all. Then later on, it returned, and I couldn’t imagine what
had done so much good, unless it could have been the lubricant, so
I told her to buy a tube, which she did. Every once in a while she
has a return of it slightly, but she just applies K-Y and clears it
all up.”
The manufacturers state that they do not know why K-Y is so soothing,
but suggest:
“Possibly the cooling action of the combination, and the effect of
the 4% boric acid contained, are factors that enter. Be all that
as it may, the fact certainly remains that oftentimes, after other
local measures fail, ‘K-Y’ lubricating Jelly gives relief.”
Elsewhere it is claimed to be germicidal, and to give relief in other
conditions, thus:
“Diabetic and uremic irritations, not only of the genitalia, but of
other parts, have been found fully as amenable as pruritus vulvae
to the soothing influence of ‘K-Y’ Lubricating Jelly, especially if
the previous application is removed with water every time a new one
is put on.”
The foregoing citations are obviously intended largely for the public,
and make it plain that “K-Y” Jelly is not in the class of nonmedical
and harmless external applications; on the contrary, these claims
tend to create the impression that the spread of measles and scarlet
fever can be _prevented_ in the stage of desquamation. To place
such statements in the hands of the patient supported by the tacit
endorsement of a prescription is to create a false and dangerous
sense of security and to lead to a failure to observe other and more
important means of preventing dissemination of these diseases.
The Council held K-Y Lubricating Jelly in conflict with Rules 1, 4, 6
and 10, and authorized publication of this report.--(_From The Journal
A. M. A., Sept. 29, 1917._)
ZIRATOL
Report of the Council on Pharmacy and Chemistry
Ziratol (Bristol-Myers Company, New York), in compliance with the
federal “insecticide law,” is declared to contain 32 per cent. water
and 30 per cent. glycerin as inert constituents. Regarding its active
constituents the manufacturer makes the following and meaningless
statement:
“Ziratol is prepared from Phenols of the Naphthalene series and
consists of a solution of such Phenols in a mixture of soap, water and
glycerin.”
In response to inquiry, the A. M. A. Chemical Laboratory examined
Ziratol and reported that its essential constituent appears to be
alpha-napthol,[120] and that it has, essentially, the following
composition by weight: Alpha-napthol 18 per cent., soap 20 per cent.,
glycerin and water sufficient to make 100 per cent.
[120] Alpha-napthol was also found to be the basis
of the nostrum Benetol. See The Journal, April 15,
1911, p. 1128.
A Ziratol advertising circular gives a tabulated report of germicidal
tests, said to have been made according to the method of the Hygienic
Laboratory of the U. S. Public Health Service. When this work was
done is not stated. According to these tests Ziratol possesses a
phenol-coefficient of 13.66. The claim that Ziratol is ten times more
efficient than carbolic acid (phenol) is evidently based on this report.
These claims of high germicidal value are contradicted by an
examination made for the Council. A specimen purchased in the open
market was examined independently by two operators, to determine the
Hygienic Laboratory phenol-coefficient. One observer found the phenol
coefficient to be 2.54. The other reported it to be 3.09. Evidently the
germicidal value of Ziratol is greatly exaggerated in the advertising
claims and, in fact, does not exceed that of the official compound
solution of cresol (Liquor Cresolis Compositus, U. S. P.) for which
a phenol-coefficient of about three has been established. (See New
and Nonofficial Remedies, 1917, p. 82.) The claim that Ziratol is
“the Universal Antiseptic and Germicide” is manifestly an unwarranted
exaggeration.
The referee in submitting this report to the Council recommended that
Ziratol be held in conflict with Rule 1 (secrecy of composition) and
Rule 6 (unwarranted and exaggerated claims). After the report had been
submitted, it was found that a new advertising circular, accompanying
a trade package, no longer contained the claim that “Ziratol is ten
times more efficient than Carbolic Acid.” The older circular made the
following statement:
“1. Strong Activity.--Compared with the bactericidal action of
Carbolic Acid by the method of the Hygienic Laboratory of the
Marine Hospital Service, ZIRATOL has the Carbolic Acid Coefficient
of more than TEN, that is, ZIRATOL is TEN times more efficient than
Carbolic Acid,--a strength unapproached by any other of its class.
ZIRATOL in dilution of 1:1400 kills the Typhoid Bacillus in 2-1/2
minutes, thus proving that it is strongly active even in very weak
solutions.”
The new advertising circular reads:
“1. Strong Activity--Extensive bacteriological investigations on
many pathogenic organisms, conducted in the Lederle Laboratories of
New York, prove conclusively the high bactericidal value of Ziratol
in extremely dilute solutions. (A copy of the complete report will
be mailed upon request.)”
In response to a request, the Bristol-Myers Company sent a copy of
the bacteriologic investigations of Ziratol, said to have been made
by the Lederle Laboratories. The organisms employed for these tests
were _Staphylococcus aureus_, _Staphylococcus albus_, _Streptococcus_,
Green pus bacillus, _B. coli_, and saliva. No tests are given with the
typhoid bacillus. The conclusion is reached that “in all the tests the
solutions of Ziratol have several times greater killing efficiency
than those of phenol.” The “coefficients” or comparative values which
can be calculated from the results after exposure of 15 minutes to the
disinfectants range from 2.0 to 4.0. This is in substantial accord
with the referee’s findings as regards the phenol-coefficient with _B.
typhosus_ as the test object. While the new advertising circular avoids
the former claim that Ziratol is ten times more efficient than carbolic
acid, in germicidal value, it still makes the unwarranted claims that
Ziratol is the “universal disinfectant.”
The Council declared Ziratol inadmissible to New and Nonofficial
Remedies (1) because its composition is secret (Rule 1); (2) because
the phenol coefficient, determined according to the method of the
Hygienic Laboratory, U. S. P. H. S., is not stated on the label (Rule
2); (3) because the label and the circular accompanying the trade
package advises its use by the public as a “vaginal douche” (Rule 3);
and (4) because the claim that Ziratol is the “universal disinfectant”
is exaggerated and unwarranted (Rule 6).
Before authorizing publication of the preceding report the Council
submitted it to the Bristol-Myers Company in order to give that company
the opportunity of revising its method of marketing Ziratol. In reply
the company enlarged on its withdrawal (on “our own initiative”) of
the claim that Ziratol had a phenol-coefficient of over ten when this
claim was shown to be incorrect “by authoritative sources.” One wonders
whether this is a euphemistic reference to the proceedings of the
federal authorities under the Insecticide Act against the Bristol-Myers
Company, just made public,[121] because of the false claims made for
the germicidal efficiency of Ziratol. This prosecution resulted in the
seizure and condemnation of two lots of this proprietary which had
passed in interstate commerce.
[121] U. S. Dept. of Agric., Insecticide and Fungicide Board, Service
and Regulatory Announcements, No. 16, issued Aug. 8, 1917. _No. 244_,
Misbranding of “Ziratol.” U. S. _v._ 100 bottles, more or less, of
“Ziratol”; consent decree of condemnation and forfeiture; product
ordered released on bond, p. 248. _No. 256_, Misbranding of “Ziratol.”
U. S. _v._ 936 bottles and 6 jugs of Ziratol, consent decree of
condemnation and forfeiture; product ordered released on bond, p. 260.
The Bristol-Myers Company in replying to the Council’s report made
no offer to declare the exact composition of Ziratol, to state the
actual phenol-coefficient, or to remove the other objections pointed
out in the report of the Council. In other words, the Bristol-Myers
Company has abandoned a definite but false claim of high germicidal
power--a claim which subjected the firm to federal prosecution--and
has substituted therefor indefinite statements which do not define the
actual germicidal efficiency of Ziratol.--(_From The Journal A. M. A.,
Oct. 6, 1917._)
GONOSAN
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report on Gonosan and authorized
its publication.
W. A. Puckner, Secretary.
Gonosan (Riedel and Company, Inc., New York City) comes in the form of
capsules, each said to contain 5 minims of a mixture composed of oil of
sandalwood 80 per cent., and 20 per cent. of alpha- and beta-resin of
kava, isolated by a patent process. The mixture, as the name implies,
is intended for the treatment of gonorrhea.
This proprietary preparation was under consideration by the Council at
various times from 1905 to 1910. During this time, the Council agreed
to accept the preparation if the suggestive name was changed, the
therapeutic exaggerations abandoned, and the drug kava admitted to New
and Nonofficial Remedies. The name was not changed, the other questions
were left open, and the preparation was not accepted.
Recent and more objectionable advertising of Gonosan makes it advisable
for the Council to take action and to publish a report. The tone of
this advertising is reflected by the following quotation from a recent
advertising circular:
“The old-established balsamic treatment of gonorrhea, for some
years neglected in favor of the local injection of organic silver
and other germicidal salts, has, with the increasing knowledge
and attention paid to the composition and purity of the balsams,
regained to a large extent the confidence formerly reposed in them.
“It may now be said that the combined treatment with local
injections and internal administration of natural balsamic products
completely dominates modern gonorrheal therapy.”
Any one conversant with current medical literature and practice would
stamp these statements as misleading exaggerations. The balsams,
oleoresins and volatile oils may have some value as minor adjuvants
in the treatment of gonorrhea, but that is all. The position in this
respect has not changed materially in recent years. These agents do not
have a value equal to that of local treatment, as the quoted statement
implies.
The claims made for Gonosan might with equal force be made for oil of
santal alone. Kava kava, the other constituent, belongs to the pepper
family; it had a temporary vogue some two or three decades ago, but has
failed to maintain a place. It has never been recognized officially.
There is no scientific evidence that it has any value either alone or
as an adjuvant to sandal oil. The “clinical reports” quoted in the
advertising circulars, rather curiously, nearly all date back ten
years or more, viz., to a period when the attitude of the profession
toward proprietary remedies was less critical than it is now. It would
be interesting to know whether these authors still adhere to their
opinion, or whether any of them have subsequently had experiences
similar to that of a correspondent who wrote:
“Gonosan, at my hands, did not prove to be of more essential
value in the treatment of gonorrhea than any other sandalwood oil
preparation. The various claims made for Gonosan, that it possesses
sedative and anesthetic properties, that by its continuous use the
urethral discharge disappears more rapidly and that, if combined with
appropriate diet and rest, it is liable to prevent complications, are,
according to my experience, not corroborated by actual results.”
The only experimental work quoted in support of Gonosan, that of Pohl,
is not convincing. The doses that Pohl found necessary to influence
experimental purulent pleurisy makes it impossible to transfer his work
to the clinic. (He found a dosage of oil of santal corresponding to an
ounce per day, for man, inefficient; positive results were obtained
only with 2 ounces per day.)
In order to learn the estimate placed on the therapeutic value of the
“balsams,” an inquiry was sent to the authors of the papers presented
to the section of Genito-Urinary Diseases at the recent meeting of the
American Medical Association in New York. The inquiry read:
“_Dear Doctor_:--An advertising circular for Gonosan ‘Riedel’ which is
now being distributed begins thus:
‘The old-established balsamic treatment of gonorrhea, for some
years neglected in favor of the local injection of organic silver
and other germicidal salts, has, with the increasing knowledge
and attention paid to the composition and purity of the balsams,
regained to a large extent the confidence formerly reposed in them.’
‘It may now be said that the combined treatment with local
injections and internal administration of natural balsamic products
completely dominates modern gonorrheal therapy.’
“Is the statement correct that the combined treatment with local
injections and internal administration of natural balsamic products
completely dominates modern gonorrheal therapy? Your reply to the above
will be appreciated by the Council.”
Seventeen replies were received. They bear out the position that
has been outlined. Only one writer considered the statement even
approximately justified, and this in the sense that “the majority
of cases receive no other treatment” than a combination of local
applications and systemic medication. Another stated that, “in a
general way their statement is true though a trifle too sweeping,” and
then added that the field of the balsams is rather restricted. With
the exception of these qualified endorsements the remaining (fifteen)
replies characterized the statement as incorrect and misleading. The
replies are a valuable contribution to the status of the “balsam”
treatment of gonorrhea, and extracts of them are appended to this
report.
It is recommended that the Council declare Gonosan inadmissible to
New and Nonofficial Remedies, because the therapeutic claims are
exaggerated (Rule 6); because there is no evidence that the combination
of kava resin with oil of santal is superior to oil of santal alone
(Rule 10); and because the therapeutically suggestive name is conducive
of indiscriminate and unwarranted use of the preparation both by the
profession and the public (Rules 4 and 8).
Appendix
The extracts from replies received to the inquiry above referred to,
follow:
Dr. B., Penn., wrote:
“In my practice I have found that local injections are very
valuable in the treatment of gonorrhea, but I have never found that
the internal administration of natural balsamics dominated modern
gonorrheal therapy; while it is an aid, I consider the quoted
statement to be very erroneous.”
Dr. F., D. C., wrote:
“While it is doubtless true that acute urethritis, gonorrheal, is
now generally treated by local injections of solutions of organic
silver salts, and that santal oil is often used, it is not true,
as one would infer from the quotation, that the balsams are now
considered more efficacious than they were formerly. So far as I
know they have not lost or regained anything during the past dozen
years in the way of confidence reposed in them. The indications for
their use is very definite and very limited.”
Dr. B., Ga., wrote:
“... In recent years I have almost abandoned the use of balsams,
etc., in the treatment of gonorrhea. Patients, who are properly
treated otherwise, seem to get along as well without such drugs
as with them, in fact apparently better for they have no gastric
disturbance. It is important for patients to drink freely of
water and when so doing the balsams are so diluted that I cannot
conceive of their doing much good. Formerly my patients often lost
weight during the treatment of gonorrhea; now, without balsams and
with plenty of water, they usually gain in weight.”
Dr. S., Mich., wrote:
“... we believe that in a general way their statement is true
though a trifle too sweeping. We do not ordinarily use the
balsams in uncomplicated anterior urethritis. We do however, find
indication for their administration in from sixty to seventy five
per cent. of all cases of acute gonorrhea at some time during the
course of the disease.”
Dr. L., Mo., wrote:
“I would say that the statement that, ‘The combined treatment with
local injections and internal administration of natural balsamic
products completely dominates modern gonorrheal therapy,’ is far
from representing the facts. While the balsamics may occasionally
have an indirect soothing effect on the mucous membranes involved,
the dominant factor is local treatment, aiming at disinfection and
restoration to normal of the inflamed tissues.”
Dr. R., Mich., wrote:
“Regarding your request although I am willing to reply it is
difficult to do so because if I should do so in the affirmative
that could apply only to certain acute cases without complication
of any kind and such cases are rare. In such, however, the
advertiser is not far from right--since vaccine therapy has proven
absolutely worthless we must fall back on antiseptics in acute
urethritis when there are no objections to such treatment ...”
Dr. K., Ill., wrote:
“I am under the impression that the internal administration of
balsamics is used only when complications arise, such as acute
posterior urethritis. Personally I use the balsamics very, very
rarely. From my observation, however, I am led to believe that many
men still use internal drugs in the treatment of gonorrhea, and
during the past few years, I should say the use of hexamethylenamin
has been on the increase, and the use of the balsams on the
decrease. I do not believe that hexamethylenamin is of any value
in the treatment of gonorrhea, and am simply citing this as my
observation of the widespread use of this drug in the treatment of
gonorrhea.”
Dr. T., Penn., wrote:
“... I believe that more men use salol or hexamethylenamin, or no
urinary antiseptic whatsoever, than use the balsamics.”
Dr. B., Ind., wrote:
“... The only systemic treatment that is considered necessary today
is rest, plenty of water and neutralize the acidity of the urine
with bicarbonate of soda or some sodium salt.”
Dr. Y., Mass., wrote:
“Sandal wood oil during the acute stage of gonorrhea certainly tends to
make the patient more comfortable and undoubtedly does lend some (tho I
believe slight) gonococcidal action. That it plays any _considerable_
part in actual cure I think is doubtful. The statement as quoted
is true in so far as it states that local treatment plus internal
medication with a balsam comprises most of the modern treatment of
gonorrhea but it is grossly misleading in that it lets one draw the
inference that the balsam plays a large if not the principal part.”
Dr. H., New York, wrote:
“For a period of at least three years in my hospital, dispensary
and private practice, I conscientiously tried out most of the
balsamics on the market (including Gonosan, which I favored for
some time) both alone, and combined with local injections. As
a result of this study, I have come to the conclusion that the
balsamics have little, if any value in the treatment of gonorrhea.
During the past few years I have relied almost entirely on local
therapy, and seldom prescribed any of the balsams in my private
practice, certainly in not more than 5 per cent. of the cases.
My results I find are just as satisfactory, and my patients
appreciate the fact that they are not loaded up with disagreeable
medication. Instead of the balsamics, I am using sodium bicarbonate
more and more, and feel convinced that the proper use of this drug
is of more value than all of them combined.”
Dr. K., Cal., wrote:
“The statement that the combined treatment with local injections
and internal administration of natural balsamic products completely
eliminates modern gonorrheal therapy, would at present not be
justifiable even with reference to the initial or acute stage
of gonorrhea, while in the subacute and chronic forms of the
disease local injections and balsams play an almost insignificant
rôle as compared with various other recognized therapeutic
measures.”--(_From The Journal A. M. A., Oct. 13, 1917_).
ALCRESTA IPECAC
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
In 1915 Alcresta Ipecac Tablets (Eli Lilly and Co.) were admitted
to New and Nonofficial Remedies as a preparation of ipecac that
is insoluble in the stomach but soluble in the intestines. It was
supposed that this property would permit the administration of ipecac
without the accompanying nausea and vomiting, and that this would be
of especial advantage when using the drug in amebic dysentery. The
systemic effects, of course, would be those of ipecac.
More recently, the manufacturers of Alcresta Ipecac have been advising
its use in conditions which were not contemplated by the Council when
the preparation was accepted for New and Nonofficial Remedies. They
now claim that ipecac alkaloids have been shown to be useful in the
treatment of typhoid fever, flatulence, diarrhea and constipation
and that Alcresta Ipecac has these properties. Such a statement
is misleading. While it is true that at one time ipecac was used
promiscuously against “flatulence, diarrhea and constipation” there
never has been and is not now any scientific evidence of its efficiency
in such conditions except, of course, in diarrhea of the amebic type.
As to the alleged usefulness of ipecac in typhoid fever: This has not
even the sanction of tradition and the claim certainly should not be
accepted until there is strong evidence to support it.
The advertising matter on Alcresta Ipecac also contained statements
to the effect that ipecac alkaloids have a demonstrated usefulness
in pyorrhea. Such an unequivocal statement is unwarranted. In spite
of the enthusiastic advocacy, in the past, of ipecac alkaloids as
a specific in pyorrhea alveolaris the preponderance of scientific
evidence indicates that ipecac is of questionable value in this
condition. Neither is there any substantial evidence to warrant the
claim that ipecac alkaloids, when absorbed through the intestines, are
demonstrably useful in amebic infections of the tonsils.
The reputation of the best drugs, whether unofficial or official,
is bound to suffer if extravagant claims for them are permitted to
go unchallenged. The referee of the Council, therefore, believed it
necessary to call the attention of the manufacturers of Alcresta Ipecac
Tablets to the statements made for the product and suggested that they
submit evidence to substantiate the claims. This the manufacturers have
refused to do. Their attitude in the matter, as well as their attitude
toward the Council’s work is expressed in the following letter:
“Responding to your letter of March 10th, we beg to suggest that
literature covering the different matters at issue are readily
available to your referee, and all statements emanating from us are
made advisedly.
“If you cannot satisfy yourselves that this preparation is a
scientific product, ethically advertised, and a desirable advance
in therapeutics, you can only delete it from your next issue of New
and Nonofficial Remedies.”
It is to be regretted that Eli Lilly and Co. refuse either to withdraw
or modify their claims or to substantiate these claims by scientific
evidence. The statements as they stand are exaggerated, misleading
and harmful. As such they conflict with Rule 6 of the Council and
necessitate the omission of Alcresta Ipecac from New and Nonofficial
Remedies. The referee recommended the adoption and publication of this
report.--(_From The Journal A. M. A., Oct. 20, 1917._)
IODEOL AND IODAGOL
Report of the Council on Pharmacy and Chemistry
Iodeol and Iodagol (formerly called Iodargol) are products of Viel and
Company, Rennes, France, widely advertised in this country by David B.
Levy, Incorporated, New York. The claim made for both preparations is
that they depend on “colloidal iodin” for their action. They are put up
in a number of forms, for instance:
“Iodeol Ampoules each containing 1 c.c. (20 centigrammes colloidal
iodin in an oily vehicle).”
“Iodeol External, containing 50 per cent. colloidal iodine.”
“Iodagol Ampoules, each containing 2 c.c. (50 centigrammes
colloidal iodine in an oily vehicle).”
The claim is, that, the iodin being in the colloidal state, it has the
properties of elementary iodin and thus the preparations may be used in
concentrations and under conditions which would make the use of free
iodin impossible. The products have been extensively and extravagantly
advertised for use in a wide range of conditions. Thus Iodeol has been
proposed in the treatment of:
“Pulmonary Tuberculosis”
“Laryngeal Tuberculosis,”
“Glandular Tuberculosis”
“Tuberculosis of the Bones”
“Pneumonia, Broncho-pneumonia, and Congestive Conditions”
“Whooping Cough, Influenza, Asthma”
“Typhoid Fever”
“Syphilis”
“Obesity.”
Iodagol, which is for external use, has been advised in the treatment
of:
“Gonorrhea and its Sequelæ”
“Cystitis”
“Tetanus”
“Wounds complicated by gaseous gangrene”
“Burns”
“Old Suppurations, ulcers, abscesses, etc.”
“Articular rheumatism”
“Abscess Alveolar”
“Pyorrhea Alveolaris”
“Stomatitis (Canker-Sores).”
Nearly two years ago the American agents requested the Council to
consider Iodeol and Iodagol for admission to New and Nonofficial
Remedies. The information submitted in regard to their character and
composition was vague and indefinite, the pharmacologic information
practically nil and the clinical data as voluminous as it was
unconvincing.
On the basis of chemical, pharmacologic, bacteriologic and clinical
investigation carried out under the direction of the referee and a
study of the submitted evidence, the referee reported:
1. Iodeol and Iodagol do not contain the amount of iodin claimed.
2. The iodin is not present as elementary iodin, but instead the
preparations behave similarly to the well-known organic iodin compounds
such as iodized fats.
3. The therapeutic claims made for the preparations are exaggerated and
unwarranted.
In view of his findings he recommended that Iodeol and Iodagol be
declared inadmissible to New and Nonofficial Remedies for conflict
with Rules 1 and 2 (misleading statements regarding composition and
identification) and Rule 6 (unwarranted therapeutic claims). The
Council adopted the recommendation of the referee, directing inclusion
of the full report in the annual Council reports after submission to
the manufacturer, and recommending publication of an abstract of this
report in The Journal.
This report was brought to the attention of the American agent, David
B. Levy, Inc., and through them to the French manufacturers, E. Viel
and Company. The manufacturers have intimated that they will not file
a reply to the report. The firm of David B. Levy, Inc., has decided to
sever its connection with these products and to discontinue their sale.
W. A. Puckner, Secretary.
Summary of Referee’s Report
Iodeol and Iodagol were submitted to the Council nearly two years ago
as “electro-colloidal iodine” and with the claim that they produced
all the antiseptic and other effects of ordinary iodin without any
of its side actions. The referee has done much work on the subject,
conducted a large amount of correspondence and has contended with
long delays. He feels that the consideration of these products should
be brought to a conclusion and accordingly he submits this report of
their consideration. The following is a summary of the report, which is
appended:
_I. Discrepancy in Iodin Percentage._--The examination at the Chemical
Laboratory of the American Medical Association, as well as that of the
referee, shows that the various samples of Iodeol and Iodagol examined
contained a little less than one-half of the total iodin claimed. These
facts were reported to the American agent. After a lengthy delay a
reply was received which presented a double excuse: (1) that the full
amount of iodin had been added, whatever had become of it later; (2)
that the claims were made for “colloidal iodin” and that this is not
elementary iodin in the colloidal state, but a preparation of iodin
containing only 50 per cent. of real iodin. Neither explanation can be
taken seriously, as they are obvious quibblings. The referee concludes
that the preparations are falsely labeled as to iodin content.
_II. Nature of the Iodin Compound in Iodeol and Iodagol._--In the
information sent the Council, Iodeol and Iodagol were defined as
“A suspension of electro-chemical colloidal iodin in a vehicle of
purified oil.” Numerous inquiries have failed to elicit more specific
information from the manufacturer or his agent. The statement of
composition can mean only that the preparations contain free iodin (but
in colloidal form) suspended in oil. No evidence to substantiate this
claim has been submitted. (There is evidence that the preparations
contain colloidal particles, but it does not indicate if this colloidal
material is iodin, or a combination of iodin or indeed whether the
colloidal component contains any iodin.) The recent statements of the
agent seem to concede that what they call “electro-colloidal iodin”
contains only about 50 per cent. of real iodin, in other words that it
is not “colloidal iodin” at all, but a mixture or combination of iodin
with some other unnamed substance. This, of course, is something very
different.
Certain results reported from the American Medical Association’s
Chemical Laboratory suggest that the so-called “colloidal iodin”
of Iodeol may be a combination of iodin with a volatile oil. The
investigations of the referee indicate that the iodin exists in a
rather resistant form or combination behaving altogether differently
from ordinary free iodin, and rather resembling the behavior of iodin
substitution products, such as iodized fats or phenols. Briefly
then the recent admissions of the agents indicate that Iodeol does
not contain “colloidal iodin” in a chemical sense, and there are
indications that it does contain its iodin in a rather firm (chemical)
combination.
_III. Chemical Properties of Iodeol._--From a study of different
specimens of Iodeol, the referee concludes that fresh specimens contain
no free iodin and that old ones contain small amounts as a result of
decomposition. Iodeol has the solubility characteristics of fats and
fat-like compounds. The examination, as a whole, shows that Iodeol
contains a peculiar and rather resistant form or combination of iodin.
There is nothing in the chemical data that suggests that it could act
differently from ordinary iodin compounds, such as iodized fats. It
would not act as ordinary iodin.
_IV. Pharmacologic Data._--The pharmacologic statements which were
submitted were loose and apparently meaningless or misleading. In
reply to questions submitted by the referee, the manufacturer finally
had some work done and submitted a report by Jean Laumonnier. The
referee was unable to confirm some of this work, and as a whole it
does not appear materially to elucidate the action of Iodeol. From a
consideration of the submitted evidence, and as a result of his own
work, the referee concludes that Iodeol does not behave like elementary
iodin; it does not coagulate proteins and therefore is not irritant. It
is presumably absorbed, but quite probably after chemical change; it is
changed into iodid and, like organic iodids, is excreted somewhat more
slowly than when inorganic iodids are administered, but the difference
does not appear important.
_V. Antiseptic and Bactericidal Action._--Elementary iodin is
considered a fairly powerful agent in these respects. The activity
is presumably due to changes in the proteins, etc., of the bacteria,
analogous to the effects which produce pain, irritation and necrosis of
the tissue cells. Since the latter effect is not produced by Iodeol,
it seems highly improbable, if not impossible, that it should act on
bacteria like elementary iodin. It is entirely unjustifiable to credit
the known antibacterial qualities of ordinary iodin to “colloid” iodin.
This misrepresentation is especially prominent in the circular “Notable
New Therapeutic Agents,” as will be seen, for instance, from the
following citations:
“Iodine has long been universally recognized as an antiseptic of
extraordinary potency. Not only is it rapid and certain in its
germ-destroying action, but it also possesses an attribute denied
many other antiseptic agents, namely, the power to penetrate and
impregnate the tissues. Other antiseptics, as is well known, act on
the surface epithelium only.”
“According to Kinnaman (J. A. M. A., Aug. 26, 1905), iodine is far
superior to bichloride of mercury, a two per cent. solution killing
streptococcus pyogenes in two minutes. Iodine does not coagulate
albumin, and is very penetrating.”
The citations imply that this “colloidal iodin” of Iodeol and
Iodagol acts as an antiseptic like ordinary iodin, except that it is
claimed to be more efficient by “diffusing” more readily. This is
entirely unjustified and misleading. If Iodeol and Iodagol are really
antiseptic, they must act by some other mechanism than that through
which elementary iodin acts, and such antiseptic action would have to
be demonstrated by direct observation and not assumed from the known
action of free iodin.
Antiseptic and bactericidal effects are easily estimated by laboratory
methods. Yet no evidence on this point appeared to have been available
until the Council called for this. Laumonnier then carried out some
experiments which were in turn submitted to bacteriologic control. The
bacteriologist failed to obtain any results with some of the tests, and
considered the other data of little value.
The claim that Iodeol and Iodagol have the antiseptic and bactericidal
action of free iodin lacks proof and must be considered unwarranted and
misleading in the extreme.
_VI. Clinical Trials._--The manufacturers and agents of Iodeol
presented many letters from physicians; but few, if any, of these gave
evidence of careful, critical, controlled observations. They could not,
therefore, be considered as acceptable evidence. The more important
claims, letters and published papers, however, were submitted to
clinical specialists collaborating with the Council, with the request
that they examine these and conduct some clinical trials, if they
considered it advisable. The results obtained in these preliminary
trials did not appear sufficient to warrant further experimentation.
From a consideration of the evidence presented, the referee concludes
that the claims made for Iodeol and Iodagol are unwarranted,
exaggerated and misleading. He recommends that Iodeol and Iodagol be
declared ineligible for New and Nonofficial Remedies for conflict
with Rules 1 and 2 (misleading statements as to composition and
identification) and with Rule 6 (unwarranted and misleading therapeutic
claims). He further recommends that the Council authorize publication
of the preceding summary of the consideration of Iodeol and Iodagol
in The Journal and inclusion of the full report in the annual Council
reports after submission to the manufacturer.--(_From The Journal
A. M. A., Nov. 17, 1917._)
CAPSULES BISMUTH RESORCINOL COMPOUND NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
In response to inquiries received, the Council took up the
consideration of Capsules Bismuth Resorcinol Compound (The Gross Drug
Company, Inc., New York City). The label, sent by the Gross Drug
Company, bore the following:
CAPSULES
BISMUTH RESORCINOL COMPOUND
Bismuth Subgallate 2 grs.
Resorcinol 1 gr.
Beta Naphthol 1/2 gr.
Creosote (Beechwood) 1 m.
This combination is of acknowledged value
in reducing the value in reducing the intes-
tinal putrefaction and fermentation, allaying
the pain and discomfort of flatulent conditions
in the intestinal tract.
DOSE.--One or two capsules before or after meals
repeated in two hours if necessary.
The Gross Drug Company, Inc.
20 Laight Street, New York
The Council held this preparation inadmissible to New and Nonofficial
Remedies or the Appendix, because (1) the claim “acknowledged value in
reducing the intestinal putrefaction and fermentation, allaying the
pain and discomfort of flatulent conditions in the intestinal tract” is
an unwarranted, exaggerated and misleading claim of therapeutic value
(Rule 6); because (2) the name does not indicate the identity of the
bismuth salt contained in the capsules, nor declare the presence of
betanaphthol and creosote (Rule 8); and because (3) the combination
of bismuth subgallate, resorcinol, betanaphthol and creosote in fixed
proportions is irrational (Rule 10).--(_From Reports of Council on
Pharmacy and Chemistry, 1917, p. 139._)
DIXON’S TUBERCLE BACILLI EXTRACT AND DIXON’S SUSPENSION
OF DEAD TUBERCLE BACILLI
Report of the Council on Pharmacy and Chemistry
New and Nonofficial Remedies, 1917, contains general descriptions
of Dixon’s Tubercle Bacilli Extract and Dixon’s Suspension of Dead
Tubercle Bacilli; the products of these manufactured by the H. M.
Alexander Company being listed as dosage forms. It having become
necessary to omit the preparations of the Alexander Company (see page
138) the referee recommended that the general articles of “Dixon’s
Tubercle Bacilli Extract” and “Dixon’s Suspension of Dead Tubercle
Bacilli” also be omitted. He reported that no other firm appears to
be marketing these products and that they had not been shown to be of
special value.
The Council accepted the recommendation and directed the omission as
proposed. In accordance with the procedure of the Council, these have
been transferred to the annual Council Reports for reference and appear
below.
W. A. Puckner, Secretary.
=Dixon’s Tubercle Bacilli Extract.=--An extract of tubercle bacilli
dissolved in normal saline solution. (See “Fluid of Dixon,” _Medical
News_, Jan. 17, 1891.)
=Dixon’s Suspension of Dead Tubercle Bacilli.=--A suspension in
physiologic salt solution of dead tubercle bacilli which have
been defatted by prolonged treatment with alcohol and ether. (See
“Possibility of Establishing Tolerance for Tubercle Bacilli,” _Medical
News_, Oct. 19, 1889.)--(_From Reports of Council on Pharmacy and
Chemistry, 1917, p. 140._)
FORMOSOL
Report of the Council on Pharmacy and Chemistry
Sunshine’s Formosol (The Formosol Chemical Company, formerly the
Sunshine Chemical Company, Cleveland, Ohio) is claimed to contain
18 per cent. formaldehyd in a solution of soap. It is therefore
very similar to Veroform Germicide which was deleted from New and
Nonofficial Remedies because of the low phenol coefficient reported by
the Hygienic Laboratory of the United States Public Health Service (The
Journal, Nov. 22, 1913, p. 1920.) The Council voted that in view of the
Hygienic Laboratory’s finding that formaldehyd has a low germicidal
value, the manufacturers of Formosol be required to produce definite
evidence of the degree of germicidal value for this product.
In submitting the preparation to the Council, it was claimed that
Formosol had “all properties peculiar to Formaldehyde.” This
conservative tone was, however, not maintained in the form-letters
submitted. These contain the following unwarranted statements:
“As the name implies, FORMOSOL is a formaldehyde preparation, which
embodies all the innate antiseptic merits and eliminates all the
ill features of the world’s greatest disinfectant.”
“The elimination of all the destructive elements and the
incorporation of all the established therapeutic virtues of
formaldehyde, have been scientifically blended in FORMOSOL.”
“FORMOSOL is unique in the sphere of antisepsis because of its
peculiar healing properties as diametrically opposed to irritation
to the tissue of mucous membrane.”
“FORMOSOL may be used for the thousand niceties of modern
antisepsis, but is _specific_ in Gynecology and Obstetrics and is
indicated in Dermatology.” [Italics not in original.]
“The constant use of FORMOSOL is to develop a habit sympathetic to
ethics.”
“To prescribe FORMOSOL is a great step toward Personal Hygiene, a
_duty of the medical fraternity_ to the laity.” [Italics not in
original.]
The trade package recommends the use of Formosol “for cuts, wounds,
ulcers, abscesses ...” This is a conflict with Rule 4. The Council held
Formosol in conflict with Rules 4 and 6, and advised the manufacturers
that Formosol is refused admission to New and Nonofficial Remedies
until they submit evidence establishing the degree of antiseptic and
germicidal efficiency, and justify the quotations listed above; or
until these and any other existing conflicts with the Rules have been
removed.
After submission of this report to The Formosol Chemical Company the
Council authorized its publication.--(_From Reports of Council on
Pharmacy and Chemistry, 1917, p. 145._)
IODOLENE, A SOLUTION OF IODIN IN LIQUID PETROLATUM,
INADMISSIBLE TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council was asked to consider a solution of iodin in liquid
petrolatum, said to be prepared from Gulf Coast petroleum by a special
process. It was to be marketed as “Iodolen” provided the Council
found the preparation admissible to New and Nonofficial Remedies. The
preparation was claimed to contain over 1.5 per cent. free iodin. The
following claims were made:
“It is less irritating in its use on the skin, or in wounds.” “Will
kill pathogenic micro-organisms present.” “Is a suitable medium for
cell proliferation.” “Will penetrate a useful distance into the
walls of a wound.” “Facilitates an easier, less painful and better
method of dressing wounds or ulcers.”
Examination in the American Medical Association Chemical Laboratory
showed a submitted sample to contain 1.32 per cent. free iodin and
to emit a strong odor of hydrogen sulphid. A specimen of liquid
petrolatum, said to be composed chiefly of hydrocarbons of the
naphthene series, after saturation with iodin at room temperature was
found to contain 1.42 per cent. free iodin. Another specimen of liquid
petrolatum, said to be composed chiefly of saturated hydrocarbons,
after saturation at room temperature was found to contain 1.30 per
cent. free iodin.
The preparation having been shown to be an unoriginal, simple
solution of iodin in liquid petrolatum, the Council declared the name
“Iodolene” unacceptable (Rule 8) and the therapeutic claims made for
the preparation unwarranted (Rule 6).--(_From Reports of Council on
Pharmacy and Chemistry, 1917, p. 148._)
KALAK WATER
Report of the Council on Pharmacy and Chemistry
The following report, submitted by a member of the Council’s committee
on chemistry, was endorsed by the committee and adopted by the Council:
Kalak Water, sold by the Kalak Water Company, Inc., New York, is an
artificial mineral water said to be made by adding certain salts to
carbonated, distilled water and supersaturating with the gas under
pressure. Such merit as it may possess by virtue of sodium bicarbonate
and sodium phosphate is quite insufficient to warrant the extravagant
claims made in the advertising pamphlets.
According to the analysis furnished, the water contains, in 1,000,000
parts (milligrams per liter) the following:
Sodium carbonate 4049.0
Sodium phosphate 238.5
Sodium chloride 806.3
Calcium carbonate 578.2
Magnesium carbonate 48.9
Potassium chloride 47.9
Among the many misleading statements found in the advertising pamphlet
bearing the title “A Brief for Physiological Alkalescence” these may be
quoted:
“The calcium content of Kalak is over 100% greater than ever before
placed in solution in any vehicle, a fact of supreme importance
when the unique alkalinizing power of the alkaline salts of this
metal is considered; the ratio of calcium metabolism to its
enormous waste in pregnancy, the diseases of infancy and childhood
and the rapidly growing group of ‘acidoses’ make its availability
in Kalak of double value.”
The first part of this statement is untrue; the last part is muddled
and without much meaning. Evidently the “acidosis” fad is to be
overworked as was the old “uric acid diathesis,” of unsavory memory.
Again this:
“One of the most important characteristics of Kalak is the close
approximation of its formula to the correlation of the contained
salts as they occur in the human body, together with its freedom
from salts foreign to the human economy. Another is its almost
unbelievable palatability, considering its high degree of
alkalinity, it being eleven times greater than any other known
mineral water, artificial or natural.”
These statements are false. The salts dissolved here bear no
discernible relation to the needs of the body, as disclosed by the
composition of the blood or solid tissues or as shown by the character
of the urinary excretion. The last statement concerning the high
alkalinity is neither clear nor accurate. Then, this warning and remedy:
“It seems to be an unappreciated fact that the degree of urinary
acidity, checked with the acidity of the saliva, is in direct ratio
to the existing acid toxemia, and a urine acid to methyl red should
be the signal for immediate and adequate alkalinizing treatment....
“Startling clinical results have been observed by physicians who
have used Kalak thoughtfully and sufficiently in the more serious
types of acidosis associated with diabetes, nephritis, rheumatism,
gout and the acute infections. There is also evidence of its good
effect in acute alcoholism and the respiratory edemas; in fact a
certain few have hailed Kalak as a possible solution of the annual
hay fever problem. Of perhaps supreme importance, however, is the
use of Kalak throughout pregnancy as preventive medicine against
the inevitable ‘toxemia of pregnancy.’”
Also this:
“Kalak has accomplished certain unexplainable things for the
diabetic and nephritic, and if, in future years, diabetes and
nephritis should prove to be constitutional diseases, based upon
functionation or its lack, Kalak therapy, the embodiment of
physiological alkalescence may come into its own, for if acidity
retards, alkalinity must normalize functionation.”
It is not necessary to quote further. In order to insure that everyone
will recognize the great need of Kalak it is advised to test the urine
for acidity by means of a group of indicator solutions sent out to the
physicians. Methyl red is one of these and any urine showing an acid
reaction with this is said to be open to suspicion. Paranitrophenol is
another of the indicators and the explanations given of the behavior of
the two and the conclusions to be drawn are questionable. The methyl
red solution furnished is too concentrated for proper use and perfectly
normal urines from normal individuals have given a rather marked color
with it. This indicator gives some color at [H+] = 1.2 × 10^{-6} and a
strong reaction at 3 × 10^{-3}. To condemn a urine on such a finding is
entirely unwarranted.
Sodium bicarbonate is the main constituent of the water. The value
of the phosphate in such a combination, with so much calcium, is
problematical. In case an alkaline reaction in the intestine is reached
some of it would be left as insoluble phosphate. A few grams of
bicarbonate daily would have equal therapeutic value with this water.
The advice based on the indications of methyl red and the urine is bad.
The committee’s report was sent to the Kalak Water Company for comment.
The company promised to withdraw the advertising circular referred to
in the report and disclaimed responsibility for the accuracy and value
of the set of indicators which it sent out, but, on the whole, the
previous advertising claims were insisted on.
In view of the absurd and false claims made for the product the Council
declared Kalak Water inadmissible to N. N. R.--(_From Reports of
Council on Pharmacy and Chemistry, 1917, p. 148._)
MINSON’S SOLUBLE IODIN “KELPIDINE” NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
Minson’s Soluble Iodin “Kelpidine” was submitted to the Council by
J. J. Minson, Washington, D. C., trading as the Kelpidine Company,
with the statement that in future “literature” it was to be known as
Minson’s Soluble Iodin, only. The following statement of composition
was furnished:
“Minson’s Soluble Iodin is somewhat of an indefinite character,
chemically. Its formula is, Iodin 4 per cent., Distilled Water
6 per cent., and Absolute Alcohol _q. s._ 100 per cent. By a
process of chilling and heating an iodid of uncertain character is
produced, and because of the extreme sensitiveness of the product
to chemical tests, it is hard to determine. So far as I have been
able to judge, however, the result is about 3 or 3-1/2 per cent.
free iodin and from 1/2 per cent. to 1 per cent. iodid, possibly
ethyl and hydrogen iodid in combination.”
The A. M. A. Chemical Laboratory reports that the preparation is an
alcoholic solution containing free iodin and iodid, probably hydrogen
iodid and ethyl iodid, but that the free iodin content was only
2.69 gm. per 100 c.c.
It is claimed that the “therapeutic indications” of Minson’s Soluble
Iodin are the “same as those of all iodin and iodid preparations,
internally, externally, hypodermically and intravenously; excepting,
however, counter irritation.” It is admitted that there are no
“clinical reports” as to the hypodermic and intravenous use, but the
belief is expressed “that in an emergency it is a safe remedy under
proper dilution.” It is further claimed that “for all practical
purposes it is nontoxic and nonirritating” and that “it has none of
the undesirable features such as is the case with the iodids and the
organic preparations of iodin, proprietary or otherwise.”
It was assigned for consideration to the Committee on Pharmacology,
whose referee reported:
“According to the information submitted, this is a tincture of iodin;
differing from the official tincture in that it is more dilute and in
that hydrogen and ethyl iodid is the solvent in place of potassium
iodid. It is practically immaterial for internal administration,
whether the cation of the solvent iodid is hydrogen, ethyl, potassium
or sodium. It would certainly be inadvisable to inject a preparation
containing free iodin hypodermically. It is not ‘a safe remedy’ for
intravenous injection and it would not be nonirritant. The statement
that ‘it has none of the undesirable features’ of other iodin compounds
is inherently impossible. Apparent freedom of any iodin preparation
from undesirable effects is generally due to the use of small doses.
Such claims are plainly therapeutic exaggerations and therefore in
conflict with Rule 6. Even should these be removed, the preparation
must be held an unessential modification of the official tincture, and
therefore in conflict with Rule 10.”
The report was agreed to by the committee and adopted by the Council
and Minson’s Soluble Iodin “Kelpidine” declared inadmissible to New
and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and
Chemistry, 1917, p. 152._)
NUTONE
Report of the Council on Pharmacy and Chemistry
NuTone (NuTone Company, Lowell, Mass.) is a “nutritive tonic” said to
have the following complex composition:
Cod Liver Oil, Pure Norwegian, 25 per cent.
Malt Extract, 9-1/3 per cent.
Beef juice,
Glycerine,
Hypophosphite Lime, Hypophosphite Soda, Chemically pure,
1-1/2 grs. each to the oz.
Fl. Ext. Nux Vomica, 3/64 of a minimum in each teaspoonful.
It is advertised with claims that will lead thoughtless physicians
and a confiding public to depend on it in cases in which fresh air,
hygienic surroundings and nutritious food are of prime importance.
A sample package (the phrase “as recommended by your physician” and
other statements suggest that it is expected to be given the patient
by the physician and thus effectively advertise NuTone to the public)
describes NuTone as an “Agreeable Concentrated Nutritive Tonic Emulsion
of Malt Extract, Beef Juice and Cod Liver Oil, Combined with Nerve
Tonics and Bone Nutrients.” Emphasizing the nutritive value of this
“Malt Extract, Beef Juice, and Cod Liver Oil” preparation, it is
advised, “As NuTone is rich in nutritive properties, it is well to
begin with one-fourth teaspoonful, gradually increasing to regular
dose, which is: Adults, 1 to 2 teaspoonfuls after meals and at bedtime.
Children according to age.” It thus appears that adults are to take
this preparation as a “nutritive” in doses which represent from 3 to
12 grains of sugar (on the assumption that malt extract may contain as
much as 50 per cent. sugar) and 8 to 30 minims of cod liver oil with
unstated, but probably equally small, amounts of beef juice.
A consideration of the negligible food value of NuTone as well as
of the inefficiency of the other components and the claim that it
is indicated in “malnutrition,” “wasting diseases” and “incipient
phthisis” classes NuTone with that large group of shotgun mixtures
which do harm in that dependence is placed on them in conditions in
which the patient will probably be restored to health if proper medical
and hygienic measures are adopted in time.
The Council declared NuTone inadmissible to New and Nonofficial
Remedies because it is an irrational shotgun mixture advertised
indirectly to the public with unwarranted therapeutic claims and a
nondescriptive therapeutically suggestive name.--(_From Reports of
Council on Pharmacy and Chemistry, 1917, p. 154._)
TRI-ARSENOLE, L. O. COMPOUND NO. 1 AND L. O. COMPOUND NO. 2
Report of the Council on Pharmacy and Chemistry
=Tri-Arsenole.=--According to the advertising of the
Medical Supply Company of Atlanta, Ga., “Tri-Arsenole” is
“Merco-Arseno-Benzo-Chloride,” and the claim is made:
“This compound is the result of many years’ research. The toxicity
has been fully tested upon animals before using clinically, the
latter having proven such complete success, we take pleasure in
presenting it to the public ...”
“The manufacturers of TRI-ARSENOL, before placing it upon the
market, tested it biologically.”
Tri-Arsenole is “recommended and suitable for the treatment of primary,
secondary, tertiary and hereditary syphilis. It has also been found
very useful in pellagra and malaria.” The preparation is supplied in
ampules containing varying amounts of the dry substance. It is to be
dissolved in water and is to be administered intravenously. In the
advertising attention is called to the yellow color of Tri-Arsenole;
this, and the style of package suggest that it is a preparation similar
to salvarsan.
In reply to a request sent the Medical Supply Company for the
quantitative composition and chemical formula of the compound
“Merco-Arseno-Benzo-Chloride” and for the details of the biologic test
by which its toxicity is claimed to have been determined and evidence
for its efficiency, the following statement was received:
“Tri-Arsenole No. 1 equals to each Ampoule, gr.
Sodium chlorid 4-1/2
Hydrarg chlor.-cor. 1/4
Arsenous acid 1/4
Sodium benzoate 4
Hydrastin (resinoid) 2
Tri-Arsenole No. 2 equals to each Ampoule,
Sodium chlorid 4
Hydrarg chlor.-cor. 1/2
Arsenous acid 1/2
Sodium benzoate 4
Hydrastin (resinoid) 2
Tri-Arsenole No. 3 equals to each Ampoule,
Sodium chlorid 3-1/2
Hydrarg chlor.-cor. 3/4
Arsenous acid 3/4
Sodium benzoate 4
Hydrastin (resinoid) 2
Tri-Arsenole No. 4 equals to each Ampoule,
Sodium chlorid 3
Hydrarg chlor.-cor. 1
Arsenous acid 1
Sodium benzoate 4
Hydrastin (resinoid) 2
The request for information regarding the animal experiments said to
have determined the toxicity was ignored, nor were references supplied
to clinical reports demonstrating the value of the product.
The Council declared Tri-Arsenole inadmissible to New and Nonofficial
Remedies because of conflict with the rules as follows:
In the absence of details of the method used, the claim that the
preparation has been tested biologically is in conflict with Rule 2,
which requires that for preparations claimed to be physiologically
standardized the method of testing must be published so as to permit of
control by independent investigators.
The claims that “Merco-Arseno-Benzo-Chloride” is “the result of many
years research,” that its “toxicity has been fully tested upon animals
before using clinically” and that clinical use has “proven such
complete success” have not been substantiated by evidence and must be
held as unwarranted.
The name is in conflict with Rule 8, which requires that pharmaceutical
mixtures shall bear names descriptive of their composition. Further,
the name “Tri-Arsenole” by its similarity to Diarsenol, the Canadian
brand of arseno-phenolamin hydrochlorid, suggests that this
pharmaceutical mixture is a chemical compound similar to salvarsan.
Moreover, the danger of confusion is increased by the addition of
the hydrastis preparation which imparts a yellow color like that of
salvarsan to the solution obtained when the colorless mercury and
arsenic compounds of the mixture are dissolved. Again, the synonym
“Merco-Arseno-Benzo-Chloride” conveys the false impression that
Tri-Arsenole is a definite chemical compound.
The label does not declare the poisonous constituents claimed to
be contained in the mixture; namely, “arsenous acid” and corrosive
mercuric chlorid (Rule 7).
There is no evidence that arsenous acid (arsenic trioxid) used
intravenously is efficient and safe as a spirocheticide, and the
administration of this drug in conjunction with mercuric chlorid
in fixed proportion is irrational and dangerous--particularly so
because of the implied similarity of Tri-Arsenole to arsenphenolamin
hydrochlorid (Salvarsan, Diarsenol) (Rule 10).
=L. O. Compound No. 1 and L. O. Compound No. 2.=--In submitting these
preparations to the Council, the Medical Supply Company stated that
“No. 1” was “composed of the following ingredients; chloral, camphor,
menthol, iodin, and oil of gualtheria, incorporated in a fatty base.
Each ounce contains fifteen grains of chloral hydrate, nine grains
of resublimed iodine.” “No. 2” was said to have the same composition
as “No. 1” except that the oil of gaultheria had been omitted. The
Medical Supply Company was informed that the rules of the Council
required declaration of the amounts of each therapeutic constituent
of pharmaceutical mixtures and that, therefore, in addition to the
information furnished the amounts of camphor, menthol and oil of
gualtheria should be given for “No. 1” and the amount of camphor and
menthol for “No. 2.” The following reply was received:
“L. O. Compound No. 1 equals to each Tube,
Chloral hydrate gr. 15
Camphor gr. 22
Menthol gr. 7-1/2
Iodin (resublime) gr. 3-2/3
Oil of gaultheria m. 3
Petrolatum, q. s. oz. 1
L. O. Compound No. 2,
The same as above formula for L. O. C. No. 1, except the oil of
gaultheria which is omitted.”
It should be noted that when the preparations were submitted each ounce
of the preparation was claimed to contain 9 grains of iodin, while
in the subsequent letter the company declares that they contain only
3-2/3 grains to the ounce. If it be assumed that the unit intended
is the avoirdupois ounce, the preparation should contain 2.06 per
cent. of iodin according to the first statement and 0.84 per cent. of
iodin according to the second statement. While the dark color of the
preparations suggested the presence of appreciable amounts of free
iodin, the A. M. A. Chemical Laboratory reported that an examination of
the specimens submitted by the Medical Supply Company showed that “No.
1” and “No. 2” each contained but 0.033 per cent. of free iodin; hence
both preparations are in conflict with Rule 1.
For both preparations the labels suggest their use for the treatment
of “septic wounds, burns, pustular processes of all varieties, and
especially bronchial troubles.” This constitutes a conflict with Rule
4. Regarding No. 1 the advertising circular included with the trade
package asserts:
“Its merits have been practically demonstrated in the following
conditions. We invite your especial attention to its use in
diseases of the thoracic cavity, especially Bronchitis and
Pneumonia, Rheumatism, Lumbago, Migraine, Neuralgia, Orchitis,
Balanitis, enlarged glands or any disturbance of the lymphatic
system, anti-galactagogue, or wherever analgesic action is
required.”
“No. 2” is said to be especially adapted to the needs of the surgeon,
it “can be applied in any wound either aseptic or infected.” It is
asserted that the usual method of preparing patients for operation may
be discarded and that patients may be operated on after application of
this ointment:
“... We have no other preparation to-day which serves the purpose
of L. O. Compound in operative and post operative treatment.
“It is a powerful antiseptic and germicide combining anesthetic,
analgesic and alterative properties.”
After attempting to discredit the approved methods of preparing the
field for surgical operations, the advertising circular continues:
“Method of today: A liberal amount of L. O. Compound No. 2 is
applied to the intended area of operation, massage thoroughly until
absorption is complete. Patient is ready for operation ...”
Both products are in conflict with Rule 6. Further, as the names of
these pharmaceutical mixtures are not descriptive of their composition,
they also conflict with Rule 8.
The use of complex mixtures such as these is irrational and leads to
misplaced confidence on the part of the physician; particularly when,
as in this case, neither the label nor the advertising matter gives the
necessary information regarding the composition of the preparations
further than that, in accordance with the requirements of the Federal
Food and Drugs Act, the amount of chloral is declared (Rule 10).
The Council declared L. O. Compound No. 1 and L. O. Compound No. 2
inadmissible to New and Nonofficial Remedies for conflict with Rules 1,
4, 6, 8 and 10.
The Council’s consideration of Tri-Arsenole, L. O. Compound No. 1 and
L. O. Compound No. 2 was based on information received from the Medical
Supply Company, the correspondence being signed “Medical Supply Co.,
per Dr. H. E. Pontius.” The findings having been sent to the Medical
Supply Company, the following reply was received:
(June 27, 1917) “Replying to your registered letter of this A. M.
relative to the Medical Supply Company’s products, will state that
the party furnishing you with such information as you have in hand
was misinformed. He is no longer with this company and whereabouts
unknown.
Respectfully,
Medical Supply Company,
(Signed) W. B. Lingo, President.”
The Medical Supply Company then was asked to point out any statements
occurring in the report, as submitted, which the company considered
to be inaccurate; but no reply has been received to this request. The
advertising sent out by the Medical Supply Company during the last
part of August contained essentially the same statements and claims as
those to which reference is made in the preceding report. A qualitative
examination of Tri-Arsenole made in the A. M. A. Chemical Laboratory
indicated the presence of sodium, mercury, arsenic, chlorid, benzoate
and a hydrastis preparation. Quantitative determinations were not made
as there was no guarantee that an analysis of the present supply would
indicate the composition of that marketed later on.
In view of the statement of the president of the company, that the
information submitted in the letters from the Medical Supply Company
was inaccurate, Tri-Arsenole and L. O. Compound must definitely be
placed with preparations, the composition of which is not divulged by
their owners; hence Tri-Arsenole as well as L. O. Compound No. 1 and
L. O. Compound No. 2 are in conflict with Rule 1.--(_From Reports of
Council on Pharmacy and Chemistry, 1917, p. 156._)
UNCTOL
Report of the Council on Pharmacy and Chemistry
Unctol, sold by the R. R. Rogers Chemical Company, San Francisco,
is a paste stated to contain approximately 40 per cent. of metallic
mercury in a soap base. It is claimed that a part of the mercury is
“precipitated mercury” and a part “mechanically comminuted mercury.”
Unctol is sold as a substitute for mercurial ointment and is to be
rubbed into the skin with the aid of water. The claim is made for
Unctol that “It is more active than blue ointment because the mercury
in it (40 per cent.) is more finely divided and the lathering still
further subdivides the mercury particles and hence promotes absorption.”
No evidence was presented to the Council in support of the claimed
superior efficacy of mercury soap paste over the official mercurial
ointment. On the other hand, a consultant of the Council who has
studied the absorption of mercury and mercury compounds, when applied
to the skin, reported that he had used mercury preparations in which
soap was the base, and that in his opinion Unctol could have no
advantage over the official mercurial ointment from the standpoint of
therapeutic effect. Moreover, the Council is advised that some trials
with Unctol at the skin clinic of Leland Stanford University Junior
School of Medicine did not confirm the claim that Unctol is more active
than mercurial ointment.
The Council declared Unctol inadmissible to New and Nonofficial
Remedies because: 1. The claim of superiority over mercurial ointment
is not substantiated, and constitutes an unwarranted therapeutic
claim (Rule 6). 2. The name does not indicate the composition of this
pharmaceutical mixture (Rule 8). 3. The circular wrapped with the trade
package advertises proprietary preparations not accepted by the Council
(Rule 4).--(_From Reports of Council on Pharmacy and Chemistry, 1917,
p. 162._)
V-E-M (SCHOONMAKER LABORATORIES, INC.)
Report of the Council on Pharmacy and Chemistry
Because of inquiry received, the Schoonmaker Laboratories, Inc., New
York, were requested to submit information in regard to the “V-E-M”
products.
According to information received, these products have the following
composition:
V-E-M Unguentum Eucalyptol Compound
Menthol 5 grs.
Eucalyptol (Sander’s) 15 gtts.
White Vaseline 1 oz.
V-E-M with Ichthyol
Menthol 2-1/2 grs.
Eucalyptol (Sander’s) 15 gtts.
Ichthyol 10 grs.
White Vaseline 1 oz.
V-E-M with Stearate of Zinc
Menthol 2-1/2 grs.
Eucalyptol (Sander’s) 15 gtts.
Stearate of Zinc 1 drm.
White Vaseline 1 oz.
V-E-M with Camphor
Camphor 15 grs.
Eucalyptol (Sander’s) 15 gtts.
White Vaseline 1 oz.
V-E-M with Boric Acid
Pulv. Boric Acid 1/2 drm.
Eucalyptol (Sander’s) 15 gtts.
White Vaseline 1 oz.
In an advertising circular this claim is made:
“V-E-M Unguentum Eucalyptol Compound Combining, in well-balanced
proportions, the cooling, soothing and healing virtues of Menthol
with the antiseptic and deodorizing properties of Eucalyptol, in a
base of pure, neutral white Vaseline. Furnished in five formulas as
follows:
“V-E-M Unguentum Eucalyptol Compound: Menthol, Eucalyptol
(Sander’s), White Vaseline.
“V-E-M with Ichthyol: Menthol, Eucalyptol (Sander’s), Ichthyol,
White Vaseline.
“V-E-M with Stearate of Zinc: Menthol, Eucalyptol (Sander’s),
Stearate of Zinc, White Vaseline.
“V-E-M with Camphor: Camphor, Eucalyptol (Sander’s), White Vaseline.
“V-E-M with Boric Acid: Pulv. Boric Acid, Eucalyptol (Sander’s),
White Vaseline.
“For local application in the treatment of affections of the nose
and throat.
“The efficacy of these combinations of remedial agents is so well
established as to preclude the necessity of more than passing
mention. What is obvious is that in acute coryza, in chronic and
acute nasal catarrh, in dry catarrhal conditions especially, in
both forms of chronic rhinitis--atrophic and hypertrophic--in the
latter stages of the prevailing grippe colds, and even in hay
fever, V-E-M Unguentum Eucalyptol Compound affords pronounced
relief and proves a most grateful application....”
Though the identity and purity of eucalyptol are provided for by the
standards of the U. S. Pharmacopeia, the claim is made that the product
contained in these preparations “transcends in purity and efficiency
all other brands.”
A package of V-E-M Unguentum Eucalyptol Compound, recently sent to a
physician, contains the following:
“If your head is all stuffed up to-night, or you feel a cold coming
on, use V-E-M just before going to bed. It will break up the cold,
and you’ll wake up in the morning, with your head clear and feeling
fine all over.
“If you suffer with chronic or acute catarrh, use V-E-M regularly
night and morning. You’ll be agreeably surprised at the relief it
will give you in a short time.
“There is nothing quicker, nothing surer to alleviate rhinitis,
grippe-colds, or hay fever.
“In a word--V-E-M is the best antiseptic ointment for all diseased
conditions of the nose....”
The Council declared these preparations in conflict with its rules
because unwarranted therapeutic claims were made for them (Rule 6);
because the public was advised to depend on them in the treatment of
diseases (Rule 4), and because these combinations of ingredients, in
fixed proportions, under proprietary names, are irrational (Rules 8
and 10).--(_From Reports of Council on Pharmacy and Chemistry, 1917,
p. 163._)
HEMO-THERAPIN
Report of the Council on Pharmacy and Chemistry
The following report on Hemo-Therapin has been adopted by the Council,
and its publication authorized.
W. A. Puckner, Secretary.
According to the Hemo-Therapin Laboratories of New York City:
“Hemo-Therapin is a combination of highly refined creosols and
phenols (which have been detoxicated by special processes) with
salts of iron, potassium, sodium, phosphorus and calcium in minute
but physiologic proportions--the solution as a whole being designed
to approximately closely in various fundamental details the
chemistry of the blood.”
No statement is made as to the quantities of the several ingredients,
nor is any information given as to the identity of the “creosols”
and “phenols,” nor the nature of the processes whereby these are
“detoxicated.” It is further claimed that it is:
“... The composite character of Hemo-Therapin, the relative
proportion and balance of its several ingredients, and the action
of the compound as a whole, to which its potency is due.”
And it is suggested that:
“It will be apparent that the ingredients which enter into
the composition of Hemo-Therapin, a remedy used intravenously
exclusively, have been selected with the utmost care with the
object of assuring not only maximum therapeutic potency but also
_absolute safety and freedom from all dangers of toxic or other
unpleasant or harmful action_.” [Italics in the original.]
The advertising does not explain, however, why the complex preparation
should be therapeutically efficient or why the intravenous
administration of this mixture should be absolutely safe and free from
toxic or harmful action. Of the origin of Hemo-Therapin it is said:
“For many years Dr. E. B. Witte, a prominent physician of Trenton,
N. J. [apparently owner of the Hemo-Therapin Laboratories] has
devoted himself to the study of the blood. As a result of his
researches, he early determined that when the blood is close to
normal standards, the body is well nourished, the natural waste
products are properly eliminated, an effective resistance is
offered to the invasion of pathogenic bacteria, and the various
functions of the body are kept normally active. But when, for one
reason or another, the blood falls away from normal standards, the
nutrition of the body suffers, the elimination of waste products
is impaired, the resistance to germ attack is weakened, and the
various functions of the body become sadly deranged and perverted.
In other words, instead of the physiologic processes of the body
being normally active, as soon as the blood is depreciated, they
become depressed or deranged, with a loss of the physiologic
harmony or equilibrium that constitutes a state of health.
“Recognizing the relation of clinical conditions to these various
phenomena, Dr. Witte reached the conclusion that the correction
of many aberrant or diseased conditions depended on restoring the
blood to as near to its normal state as possible. He accordingly
applied himself especially to investigation of the chemistry of
the blood, with the object of evolving a substance in liquid form
that would so closely approximate normal blood in its essential
chemical characteristics that when introduced into the circulation
it would bring the blood nearer to the condition in which it exists
in health.”
After the usual “many years of hard painstaking labor,” Dr. Witte
elaborated a “fluid meeting the foregoing conditions” and now the
Hemo-Therapin Laboratories inform us that 5 to 10 c.c. of this
synthetic blood administered once in one, two or three days in “acute
affection” and at longer intervals in “chronic ills”--once a week is
said to be usually sufficient--will restore blood to a normality and
empower it to overcome most ills. While disclaiming that “Hemo-Therapin
is an infallible panacea,” the medical profession is asked to believe
that:
“In erysipelas, septicemia, pyemia, the acute fevers, puerperal
infection, furunculosis, carbuncles, malaria, acute rheumatism,
pneumonia, typhoid fever, and in various skin diseases, such as
eczema, psoriasis, herpes zoster, etc., the results have been
prompt and gratifying.”
It is “no less effective” in such “chronic ailments” as:
“... diabetes, chronic Bright’s disease, goiter, pulmonary
tuberculosis, chronic rheumatism, the severe anemias,
arterio-sclerosis [_sic_], various nervous disorders, locomotor
ataxia, varicose and indolent ulcers....”
Evidence of the virtues of Hemo-Therapin is submitted as a series
of “case reports”--unsigned--which bear a striking likeness to the
testimonials of “patent medicine” almanacs. A specimen of the “case
reports” is the following:
“_Blood Poisoning due to Snake Bite._--Case 9.: Mrs. ----; age, 52;
was bitten by a poisonous snake--a copperhead--seventeen years ago.
On the anniversary of the bite the arm would swell to more than
twice its normal size and there would be pain, chills and fever.
After a month of this the acute symptoms would disappear and the
arm would show large scaly blotches which upon being removed would
disclose a thin mucous liquid. Throughout the seventeen years pain
was constant, being particularly acute in midsummer around the
anniversary of the bite. This patient had consulted many physicians
during the seventeen years of suffering without any relief. Large
doses of narcotic remedies were necessary each day to subdue the
pain. Twenty-four hours after the first injection of Hemo-Therapin
all pain was dissipated. After four treatments the patient was
considered well and there has been no return of any of the symptoms
since the last treatment six months ago.”
Hemo-Therapin is sold in ampules: 6 for $5 and 12 for $10, and a
circular sent to a physician contained this typewritten note:
“FEES.--While the physician’s fee is not regulated by this company,
the physicians who use Hemo-Therapin get $5.00 and $10.00 for each
treatment.”--(_From The Journal A. M. A., Jan. 5, 1918._)
VENOSAL
Report of the Council on Pharmacy and Chemistry
The following report on Venosal has been adopted by the Council, and
its publication authorized.
W. A. Puckner, Secretary.
“Venosal” is one of the products of the Intravenous Products Company,
Denver, Colo. Its composition has been variously, and obscurely,
described:
“Venosal is a sterile solution representing 1 gm. (15.4 gr.) of
salicylates in combination, together with colchicum.”
“This is a product for intravenous use. The composition of which
is Sodium Salicylate, 15.4 grs. (1 gm.), Iron Salicylate a minute
quantity and the equivalent of approximately 2 grs. Dried Colchicum
Root.”
None of these “formulas” gives the quantity of the product containing
the 1 gm. of salicylate, etc., but presumably it refers to the contents
of 1 ampule or 20 c.c. This inference is in accord with the analysis
of the product made in the Chemical Laboratory of the American Medical
Association. The analysis also brought out the fact that the amount of
iron in a given ampule was 0.0008 gm. (about 1/80 grain). This trace of
iron in the presence of salicylate gives the product a purple color.
Venosal is recommended for the treatment of “rheumatism,” meaning, the
context would indicate, infectious rheumatic fever. As colchicum has
no special action on this disease and as there is no apparent reason
for the employment of the trace of iron present, these additions in
fixed proportions are unscientific, if not absurd. According to the
advertising matter:
“Venosal ... eliminates unpleasant digestive disturbances which
frequently forbid the use of salicylates by mouth and, in addition,
insures their full therapeutic value.”
The statement is misleading, as the cases in which the oral
administration of the salicylates is contraindicated are not “frequent”
but exceptional and there is no evidence to justify the implication
that the “full therapeutic value” of salicylates cannot readily be
attained by their oral use. Still more astonishing is the following
claim:
“Venosal is a combination carrying the true salicylates (sodii)
in doses much larger than given by mouth. With this preparation
given intravenously, there is no nausea or disagreeable digestive
after-effects, tinnitus aurium, or the accumulating effects of
the drug; yet the specific action of the salicylates seems to be
increased many-fold, according to reports received.”
What are the facts? By mouth sodium salicylate is given in doses of
from 3 to 15 gm. in a day; whereas Venosal is advised as 1 gm., in
from one to three day intervals; as a matter of elementary arithmetic
it is plain that these doses of Venosal are smaller instead of being
“much larger.” The absence of digestive ill effects, tinnitus, etc.,
is explained by the small dosage. That the specific action of the
salicylates should be increased by intravenous administration is
surprising when it is remembered that the drug is absorbed rapidly
and completely from the intestines; in fact, the quoted statement is
incredible.
The company further alleges that, on the basis of “clinical reports”
it has received, it does not “hesitate to recommend this product for
routine use in all streptococcic infections.” Such a therapeutic
suggestion is, to put it conservatively, gross exaggeration.
The whole question of the justification of using salicylates
intravenously is open to grave doubt. Since it is possible to obtain
the salicylate effects promptly and certainly by oral administration,
the inherent dangers of intravenous medication render its routine
employment unwarranted. A further objection to Venosal, especially at
this time when economy is a national policy, is the unnecessarily high
expense of Venosal itself and of its administration.
The referee recommends that Venosal be declared ineligible to New and
Nonofficial Remedies because of conflicts with Rule 1 (indefinite
chemical composition), Rule 6 (therapeutic exaggerations) and Rule
10 (unscientific composition).--(_From The Journal A. M. A., Jan. 5,
1918._)
SECRETIN-BEVERIDGE AND THE U. S. PATENT LAW
Report of the Council on Pharmacy and Chemistry
Two years ago the Council published reports on two proprietary
preparations said to contain secretin, namely, “Secretogen,” sold
by the G. W. Carnrick Company (The Journal A. M. A., May 1, 1915,
p. 1518), and “Duodenin,” sold by Armour and Company (The Journal
A. M. A., Aug. 14, 1915, p. 639). These reports explained that there
was no evidence to indicate that an insufficient amount of secretin was
the cause of gastro-intestinal diseases, and further that there was
no evidence that secretin in any form was physiologically active when
administered by the mouth.
Subsequently, A. J. Carlson and his co-workers, at the request of
the Council, studied the question of the stability of secretin and
demonstrated (The Journal A. M. A., Jan. 15, 1916, pp. 178 and 208)
that commercial secretin preparations contained no secretin and,
further, that secretin given both by the mouth and even in enormous
doses directly into the intestine is entirely inactive.
Shortly after the publication of Professor Carlson’s work the attention
of the Council was called to a U. S. patent issued, May 2, 1916,
to James Wallace Beveridge, “Means for and Method of Stabilizing
Secretin.” In this patent Beveridge claimed to have invented “The
process of producing secretin in stable form as a commercial article
for therapeutic use ...” that is, a process for preparing preparations
which would contain secretin when they reach the consumer and in a form
resisting destruction in its passage through the stomach.
In view of the demonstrated instability of secretin, the Council
asked Professor Carlson to investigate the validity of the claims of
the Beveridge patent. The study on “The Question of the Stability of
Secretin,” by A. J. Carlson, A. E. Kanter and I. Tumpowski, which
appears below, shows that the Beveridge patent furnishes no process for
the manufacture of commercially stable secretin preparations, nor any
means for preventing the destruction of secretin by the gastric juice
when administered orally. It further demonstrates that the preparation
made by Beveridge was devoid of secretin.
The Council adopted the report of Carlson and his co-workers, and
declared Secretin-Beveridge inadmissible to New and Nonofficial
Remedies.
The Council directed that the report of Carlson and his collaborators
be sent to the Commissioner of Patents with a protest against the
granting of patents without competent and thorough investigation of the
claims advanced therein.
W. A. Puckner, Secretary.
THE QUESTION OF THE STABILITY OF SECRETIN
A. J. Carlson, A. E. Kanter and I. Tumpowski
[From the Hull Physiological Laboratory of the University of Chicago]
In a letters patent, filed May 6, 1914, the patent granted May 2, 1916,
James W. Beveridge, M.D., makes certain claims concerning the stability
and physiologic activity of secretin prepared according to the method
patented by him.
In brief, Dr. Beveridge claims that secretin prepared by digesting
intestinal mucosa with a weak acid at a temperature slightly below
boiling, and mixed with 0.2 per cent. to 2 per cent. blood serum,
albumin or peptone (1) remains active for at least six months, (2)
stimulates the pancreas when given by mouth, and (3) “may be injected
intravenously in man, if desired.” The only thing in the letters patent
in support of these claims is the statement: “I have found out by
actual tests that the preparation maintains its stability for five or
six months.”
Here are the claims in detail:
“For the source of secretin I preferably use that part of
the alimentary tract of any lower animal--such as a hog or
sheep--including the gastric pylorus, the duodenum and the jejunum.
This part is split open and washed with a normal saline solution to
clean the mucosa or mucous membrane of any detritus which may be
present. The mucosa with the epithelial cells is then removed or
separated from the muscular wall by scraping with a blunt knife or
in any other suitable way. The scrapings or cuttings, which contain
the secretin, are then macerated or broken up.”
“The macerated mass is placed in a suitable vessel and subjected
to the action of an acid solution until digested. The time for the
digestion of the mass will, of course, depend upon the strength
and temperature of the acid solution employed. The stronger the
solution and the higher the temperature, the shorter the time
necessary for complete digestion. This period may vary from several
minutes to several hours. In my experiments I found that the best
results were obtained with hydrochloric acid solution of one-tenth
to five-tenths of one per cent. in strength, although as high as
eight-tenths per cent. might be used. The mixture is brought to
a temperature of approximately 210 F., and it may even for a few
moments exceed that temperature, but it should be kept below the
boiling point, for excessive heat injures or breaks down the
secretin molecule and impairs or destroys its activity. Although I
prefer to use hydrochloric acid, I would have it understood that
other acids--both organic or inorganic--may be employed, provided
that the percentage of acidity is regulated to prevent a chemical
change in the secretin, and further provided, of course, that the
acid has no injurious effect on the human system.”
“After the mass has been digested in the heated solution, the
decoction is decanted, and after being allowed to cool is passed
through a suitable filter until the filtrate is clear. I found that
by filtering the decoction from four to six times through a carbon
filter, I obtained a clear colorless filtrate. This is a solution
of secretin and the acid which was used, and the clearness of the
solution shows that it is practically free from albumoses, gelatin
and other impurities (such as cell tissues, etc.) present in the
raw material under treatment.”
“To the solution of pure and active secretin prepared as above
explained, there is added a suitable quantity of blood serum--say
from one-fifth to two per cent. or any equivalent medium--such as
albumin solution or a peptone solution--which will aid and sustain
the activating power of secretin as provided by the blood. That
is to say, any medium having the same power, similar quality or
chemical composition that the blood-stream possesses in combining
with secretin to stimulate the pancreas. The addition of such a
medium to the active secretin solution increases the potency of
the secretin and its degree of stability by preventing oxidation
or deterioration thereof. If this strengthening or fortifying
medium, as it may be properly termed, is alkaline, it performs
the additional function of lowering the acidity of the secretin
filtrate. It is preferable that the final product be just faintly
acid. If desired, the final product may be made into an elixir by
the addition of aromatics.”
“Any desired strength of secretin solution may be obtained
according to the quantity of acid solution. In my experiments I
used from ten to fourteen duodena to a pint of acid solution.”
“The solution of secretin prepared as above described is
characterized by its ability to resist oxidation or deterioration
for a sufficient period of time to render the solution available as
a commercial article, and is furthermore characterized by freedom
from poisonous and irritable chemical substances, whereby the
secretin is chemically adapted to the human system to stimulate the
pancreas to increased secretion.”
“As previously stated, the secretin prepared according to my method
may be administered orally to produce the desired physiological
action. Of course, if desired, the secretin might be injected
intravenously, but this more or less dangerous procedure is not at
all necessary, and I merely mention it here to point out that when
I refer to the oral administration of my new secretin preparation,
I do not mean to exclude its administration by injection.”
“As to the commercial stability of the secretin prepared according
to my method, I may say that I have found by actual tests that the
preparation maintains its stability for as long a period as five
or six months. When I refer to my product as being “commercially
stable,” I mean that it resists oxidation or deterioration for a
sufficient period to render the same available as a commercial
article. This period may vary from several weeks to several months,
depending upon certain commercial factors well understood by the
manufacturer. So, roughly speaking, I should say that secretin is
commercially stable when it retains its activity from one to six
months. I do not wish to be understood, however, as limiting myself
to these exact figures.”
That active secretin may be extracted from macerated intestinal mucosa
by weak acids below the temperature of boiling is well known. In fact,
weak acids at body temperature in contact with the duodenal mucosa lead
to the formation of secretin. The claims that secretin given by mouth
reaches the blood and acts on the pancreas has been made for other
preparations of secretin. It has also been shown that these claims are
erroneous.[122] Thus it would appear that the only novel element in
Dr. Beveridge’s patented secretin is the addition of serum, soluble
proteins or peptones. What reason is there for believing that this
will render the secretin stable for months, and physiologically active
when taken by mouth? We do not believe Dr. Beveridge ever injected his
secretin--protein mixture--intravenously in man or animals not under
anesthesia, otherwise he would not have stated: “Of course, if desired,
the secretin may be injected intravenously.”
[122] Carlson, Lebensohn and Pearlman, The Journal, Jan. 15, 1916,
p. 178.
BEVERIDGE’S PATENTED SECRETIN IS NOT STABLE
I. _The Samples of Secretin Sent Us by Dr. Beveridge._--Physiological
tests were made on four quart bottles of the secretin kindly sent us by
Dr. Beveridge June 26, 1916. According to a letter from Dr. Beveridge
of July 20, 1916, those samples of secretin were prepared June 20, that
is, only six days before received by us. The material came in dark
colored bottles. It was kept in the original bottles and placed in
the ice box immediately on receipt. Dr. Beveridge stated the secretin
“should remain active until the month of November, 1916, at least.”
Tests were made on three out of the four bottles. The fourth bottle
was not opened, as we desired to learn what change it might undergo
in the way of protein precipitation and bacterial decomposition.
There is nothing in the Beveridge method of preparation that insures
a sterile secretin unless it is passed through a Berkefeld filter.
In all our crucial experiments the animals (dogs) were kept under
light ether anesthesia, a cannula inserted into the pancreatic duct,
the blood pressure recorded from the carotid artery and the various
secretin preparations injected intravenously. When inactive secretin
preparations were encountered, control tests were always made with
active solutions of secretin to eliminate possible individual
peculiarities of the animal. Thus when the pancreas of a dog reacts to
the injection of preparation _A_, but not to preparation _B_, it is
evident that absence of response to _B_ is due to this preparation and
not to the animal or to the experimental conditions.
[Illustration: Fig. 1.--Records of carotid blood pressure and secretion
of pancreatic juice on intravenous injection of Beveridge’s secretin
in dogs. _X_, injection of 10 c.c. secretin; _b_, record of flow of
pancreatic juice in drops. Tracing _A_, injection of 10 c.c. of one
sample secretin (ten days old) furnished by Dr. Beveridge. Tracing
_B_, injection of 10 c.c. of second sample of secretin (ten days
old) furnished by Dr. Beveridge. Tracing _C_, injection of 10 c.c.
of secretin (twenty hours old) made by us according to the Beveridge
method. Showing that the secretin preparations sent us by Dr. Beveridge
contained no secretin.]
Each of the three samples of secretin sent us by Dr. Beveridge was
tested in the above manner on five dogs. The first tests were made
June 27, 28 and 29, respectively, that is, within nine days of the
preparation of these samples of secretin. _None of the samples was
active (Fig. 1), even when injected intravenously in quantities up to
50 c.c._: 40-50 c.c. of Beveridge’s secretin mixture may kill a dog by
too great lowering of the blood pressure. A good secretin preparation
yields a copious secretion of pancreatic juice on intravenous injection
of a few cubic centimeters.
It is not difficult to prepare a secretin, by the original Bayliss or
Starling method or by the Beveridge method, that retains some activity
for a longer period than nine days. Hence we cannot account for the
absolute inactivity of these preparations except on the assumption
that they did not contain any secretin to start with; that is, faulty
preparation and absence of physiologic standardization.
The sample kept intact in its original container for six months became
gradually cloudy, a large mass of amorphous precipitate settled
to the bottom and the odor showed bacterial decomposition. It is
reprehensible, to say the least, to state concerning such a mixture:
“Of course, if desired, it may be injected intravenously.” The fact
that Beveridge’s secretin may be rendered clear by filtering through
carbon is not sufficient evidence that it is “pure secretin,” free from
bacteria and other injurious substances.
II. _Beveridge Secretin Mixture Is Rapidly Rendered Inactive by Human
Gastric Juice._--We prepared active secretin solutions by the Beveridge
method, using 0.2 per cent. serum as the protein “stabilizer” (?).
The addition of the serum does not appear to affect the activity
of the fresh secretin preparation. If Beveridge’s secretin is able
to act on the pancreas when given by mouth, it is obvious that it
must run the gamut of gastric digestion, except in cases of complete
achlorhydria. It has been repeatedly demonstrated that all other
secretin preparations are rapidly destroyed by pepsin-hydrochloric acid
digestion. Is Beveridge’s secretin an exception? What is there in a
little serum, native albumin, or peptones to protect secretin against
gastric digestion?
The pure human gastric juice used in these tests was secured from
the fistula case (Mr. F. V.) that has been under observation in our
laboratory for years.[123]
[123] Carlson: The Control of Hunger in Health and Disease, Chicago,
1916.
BEVERIDGE’S SECRETIN AND BAYLISS-STARLING SECRETIN PREPARED
Sept. 29, 1916
================================================================
Response of Pancreas
(No. of Drops of Secretin)
Date of Test Quantity of ┌───────────┴───────────┐
Secretin Bayliss-Starling Beveridge
Injected, C.c. Secretin Secretin
Sept. 29. 10 75 78
Oct. 2. 10 61 61
Oct. 6. 10 28 17
Oct. 13. 10 25 31
Oct. 27. 10 5 6
Nov. 3. 10 7 6
Nov. 17. 10 4 5
Nov. 30. 10 3 4
Dec. 4. 10 2 2
Dec. 20. 10 0 0
----------------------------------------------------------------
_Two cubic centimeters of fresh gastric juice added to 8-10 c.c.
Beveridge secretin, the mixture being kept at body temperature
(38 C.), renders the secretin completely inactive in from 5 to 8
minutes_ (Fig. 2). There is no exception to this rule, as we have
repeated the test on many different secretin preparations and using
different samples of human gastric juice. The secretin of Beveridge
is just as vulnerable as the secretin of Bayliss and Starling to
pepsin-hydrochloric acid digestion. On what kind of tests does
Beveridge base his claim that his secretin mixture acts on the pancreas
when given by mouth?
III. _The Relative Rate of Deterioration of the Secretin Solutions
Prepared According to Bayliss and Starling and According to
Beveridge._--Six different preparations of the two kinds of secretin
were made, kept in dark stoppered bottles in the ice box, and tested by
intravenous injection in dogs under ether anesthesia from time to time
until all influence on the pancreas had been lost. One typical series
of these tests is given by the way of illustration. (See Table on page
126.)
[Illustration: Fig. 2.--Records of carotid blood pressure and flow of
pancreatic juice on intravenous injection of secretin prepared by us
according to the Beveridge method. _X_, injection of 10 c.c. of the
secretin; _b_, record of flow of pancreatic juice in drops. Tracing
_A_, the 10 c.c. of Beveridge’s secretin injected had been digested for
five minutes with 3 c.c. of human gastric juice. Tracing _B_, injection
of 10 c.c. of the same secretin preparation not subjected to gastric
digestion. Showing rapid and complete destruction of Beveridge’s
secretin by human gastric juice.]
It will be seen that the rate of deterioration (oxidation or
decomposition) of the secretin is practically the same whether prepared
according to Bayliss and Starling or according to Beveridge (Figure 3).
In both preparations the rate of deterioration is most rapid the first
few days after preparation. It is scarcely necessary to point out that
secretin preparations not kept constantly at low temperature and in the
dark, as in the above experiments, will deteriorate more rapidly.
[Illustration: Fig. 3.--Records of carotid blood pressure and flow of
pancreatic juice on intravenous injection of secretin preparations.
_X_, injection of 10 c.c. secretin; _b_, record of flow of pancreatic
juice in drops. Tracing _A_, secretin prepared according to the
Beveridge method September 30. _I_, injection of 10 c.c. October 2.
_II_, injection of 10 c.c. November 30. Tracing _B_, secretin prepared
by the Bayliss-Starling method September 30. _III_, injection of
10 c.c. October 2; _IV_, injection of 10 c.c. November 30. Showing no
greater stability of Beveridge’s secretion over that of Bayliss and
Starling.]
Why can we hope that the addition of serum or any solution of protein
will render secretin more stable? In the intact man or animal under
normal conditions of digestion, secretin reaches the pancreas by way
of the blood, that is, it is in solution in blood. Does that fact
render the secretin stable? By no means. The reader is familiar with
the fact that the response of the pancreas to a single intravenous
administration of secretin is very transitory (5-15 min.). The
cessation of activity is due, not to fatigue of the pancreas, as a
second injection of secretin gives a prompt response of pancreatic
secretion, but to the disappearance of active secretin from the blood.
In fact, secretin left in the test tube or in the bottle remains active
over a much longer period of time than when introduced into the blood
stream.
IV. _Beveridge’s Secretin Given by Mouth to the Intact Animal Has No
Specific Action on the Pancreas._--Active secretin prepared according
to the method of Beveridge was fed on an empty stomach to a small dog
(5 kilo) with permanent fistula of one of the pancreatic ducts. On
control days we gave the dog (_a_) equal quantities of n/10 HCl, and
(_b_) bread and milk. The Beveridge secretin was prepared with 0.3 per
cent. HCl and the addition of 0.2 per cent. serum. The results may be
stated by the following summary:
GIVING BEVERIDGE’S SECRETIN BY MOUTH
================================================================
Secretin of the
Number of Pancreas for Three
Material Fed Tests Hours Following
the Feeding
150 c.c. Beveridge Secretin 6 10.2 c.c.
150 c.c. n/10 HCl 5 22.7 c.c.
Bread soaked in milk 4 6.6 c.c.
----------------------------------------------------------------
The Control experiments with pure hydrochloric acid show that the
secretion of pancreatic juice following the introduction of Beveridge’s
secretin into the stomach is due to the acid factor and the protein
content.
CONCLUSIONS
The patented secretin of Beveridge is rendered inactive by gastric
juice, is without effect when given by mouth, and exhibits no greater
stability or keeping qualities than the secretin prepared according
to Bayliss and Starling. It has no merit as a therapeutic agent.
It should under no conditions be administered intravenously in
man, as it contains deleterious protein split products and living
bacteria.--(_From The Journal A. M. A., Jan. 12, 1918._)
NEED FOR PATENT LAW REVISION
Report of the Committee on Patent-Law Revision of the Council on
Pharmacy and Chemistry of the American Medical Association
At the present critical time when the efficiency of this nation must
be raised to the highest point, it is essential that the United States
government should lead in the efforts tending to such increased
efficiency. To bring this about the government must protect and
stimulate science, art and industry and at the same time curb or
prevent waste of the country’s resources. In this field the United
States Patent Office has unlimited power for good and evil--good, in
the issuance of patent grants for novel devices and substances which
go to increase national efficiency; evil, in the granting of patent
protection where such protection is not in the interest of national
efficiency, conservation of energy and material resources.
For years the American Medical Association, in common with the
national pharmaceutical bodies, has been urging amendment of the
law which governs the issuance of patents on medicinal preparations
and more particularly revision of the procedure under which such
patents are issued. At the Chicago (1908) meeting of the American
Medical Association a special committee of five was appointed by
the House of Delegates to study the questions involved, and to
cooperate with the Association’s committee on medical legislation in
preparing and securing the enactment of a bill which would correct
the abuses connected with the enforcement of our patent laws (The
Journal A. M. A., June 13, 1908, p. 2003). This committee presented
a comprehensive report at the Atlantic City (1909) meeting of the
American Medical Association (The Journal A. M. A., June 19, 1909,
p. 2063). A further report was presented at the St. Louis (1910)
meeting of the American Medical Association (The Journal A. M. A.,
June 18, p. 2079). In 1911 (The Journal A. M. A., Nov. 25, 1911,
p. 1780) the Council on Pharmacy and Chemistry of the American Medical
Association issued a report which set forth the inadequacy of our
patent laws as they are administered in relation to medical products
particularly.
AGAINST PUBLIC INTEREST
Since that time the Council has continued its study of the U. S. Patent
law as it applies to medicine and has become convinced that in many
instances the patent law or its enforcement is contrary to the best
interest of the public, both as concerns health and prosperity. The
Council feels it a duty at this time to protest against the provisions
of our patent law, or the methods of its enforcement, which permit the
granting of patents without thorough and scientific investigation of
the claims advanced in such letters patent. As one means of improving
conditions the Council urges that the U. S. Public Health Service,
the Bureau of Chemistry, U. S. Department of Agriculture and other
scientific departments of the United States government conversant with
medicines and related subjects be consulted before the issuance of
patents on medicinal preparations.
In support of the Council’s contention that the patent law procedure
requires revision, the following is offered: In 1912 a U. S. Patent
(No. 1,031,971) was granted on a cresol derivative, metacresyl acetate,
a product described in chemical literature in 1903. When the Council
inquired as to the grounds for the issuance of a patent for a substance
known to science, the Patent Office replied that it was not familiar
with the publication in which metacresyl acetate had been described.
It seems evident that this patent would not have been issued had the
application first been submitted to a government department familiar
with chemical literature.
An illustration of the granting of a patent on the use of well-known
chemical bodies which present no discovery or originality, is the
patent issued for the use of peroxids, perborates and percarbonates as
ingredients of tooth powders (U. S. Patents Nos. 760,397 and 802,099).
Regarding these patents The Journal of the American Medical Association
(Sept. 20, 1913, p. 978) commented:
“The patents held by McKesson and Robbins give this firm the
exclusive right of manufacturing tooth powders containing peroxids,
perborates and percarbonates. It is another illustration of the
unfair monopolies that may be secured under our present patent
laws.”
GRANTING A PATENT TO A NOSTRUM
Again in 1913 U. S. Patent No. 1,081,069 was granted to a citizen
of Switzerland (a country which does not grant patents on medicinal
preparations) for a “composition which is intended to be used
internally and which confers to the organisms immunity against the
following microbial infectious illnesses: _diphtheria, pneumonia,
typhus, scarlet fever, influenza, septic infections, cerebral-spinal
meningitis, syphilis, pest, cholera and tuberculosis; it is also
effective in another kind of disease, viz., goiter_.” (Italics not in
original). The patent specification states that “The principal of these
substances is creatinin ...,” but offers no evidence whatever that
this well-known chemical body has the extensive and miraculous powers
claimed for it. In publishing a notice of this patent The Journal of
the American Medical Association (Jan. 3, 1914, p. 54) explained:
“It appears that the inventor is dead, and that his estate took out
the patent. Since this great benefactor should have been, by the
use of his preparation, immune to practically all diseases, he must
have died of senility, although this seems hardly to have been the
case.”
and held:
“Assuredly granting patents on such claims ought to be sufficient
to show the need of a change in the methods of granting patents--at
least of the methods governing the issuance of patents for
medicinal products.”
We submit, that had the department of the government entrusted with
the enforcement of the federal Food and Drugs Act been consulted as to
the claims of this patent, it would probably have advised that, if the
absurd and palpably fraudulent claims set forth in this application for
a patent were made on the label of a preparation of creatinin offered
for sale in interstate commerce or in the District of Columbia, the
vendor would be prosecuted.
In 1914 there was issued U. S. Patent No. 1,086,339. Here the
“inventor” declared:
“It is the object of my invention to destroy parasitic
micro-organisms, particularly on living tissue without injuring
the latter, by progressively evolving sodium hydroxid contiguous
to said tissue, from and in a moist mixture of calcium hydroxid,
sodium carbonate, aluminum sulfate and boric acid....”
In a word, this patent apparently was granted for the production of
sodium hydroxid by a chemical reaction which had been in use for
several centuries. Because the patentee had twisted the granting of
this patent into a quasi-endorsement of his nostrum, the Council’s
consideration of this preparation was sent the Patent Office as a
protest against the present law which authorizes the granting of
patents on unproved and improbable medical claims. At that time the
Council was informed by the Patent Office that reforms in the issuance
of patents for medicinal substances had been instituted, and that “the
trouble will not be so pronounced in the future as it has been in the
past.”
FLAVORING EPSOM SALT A “DISCOVERY”
There was issued early in 1917 U. S. Patent No. 1,212,888 for a method
of flavoring Epsom salt--yet this “discovery” is a procedure which has
been practiced ever since the cathartic action of this bitter salt has
been known. Not only does the patent describe a process long known to
physicians and pharmacists, but it sets forth claims that the flavored
cathartic salt produced by the process cures flatulency, indigestion,
sick and sour stomach, colic and destroys worms. In commenting on this
patent The Journal of the American Medical Association (June 23, 1917,
p. 1914) was constrained to remark:
“The splendid conception of the framers of our constitution in
providing a plan for promoting progress in science and useful arts
by granting to inventors for a limited time the exclusive use of
their inventions, in exchange for the publication of full knowledge
thereof, is being debased. No branch of our government is of
greater importance to the progress of the country than the patent
office, provided that office is intelligently administered. When
the patent office is used, however, for an extension of the nostrum
business, founded on the abuse of patent and trade-mark laws, it
becomes a menace to the public health. The objects of the patent
law are being defeated by the practices of the patent office.”
Still further, attention is called to U. S. Patent No. 1,226,394 for
a process of making hexamethylenamin tetraiodid and on the product so
produced. This patent was issued after the Council had notified the
Patent Office that hexamethylenamin tetraiodid had been discovered in
1888 and that a process identical in principle with that for which
patent application appeared to have been made was published in 1916.
On the basis of claims for which no evidence is produced this patent
is issued for a well-known substance on the ground that as previously
produced it contained a little free iodin or that the known processes
were less economical. This patent appears to be an illustration of
our patent procedure which obliged American users of acetylsalicylic
acid to pay an exorbitant price because this country granted a patent
which gave to the patentee, a foreigner, the exclusive right to the
manufacture of the substance, whereas no such patent was issued in
the patentee’s own country nor, so far as we can learn, in any other
country. It forcibly illustrates the need for a revision either of our
patent laws or of their methods of enforcement or both.
THE BEVERIDGE PATENT
In further justification of the Council’s protest against the
provisions of our present law, or the methods of its enforcement,
which permit the granting of patents without thorough and scientific
investigation of the claims advanced in such letters patent, the
Council calls attention to the report, appearing above, of an
investigation made by A. J. Carlson, A. E. Kanter and I. Tumpowski,
“The Question of the Stability of Secretin,” which relates to U. S.
Patent No. 1,181,424, issued to James Wallace Beveridge.
Whereas the regulations governing the issuance of patents demand
that the processes shall be described in such detail that one versed
in the sciences can confirm the claims made by the patentee, no
pretense whatever of fulfilling this requirement is made in the patent
specifications of this patent. The substance of the first three
paragraphs of this patent has long been general knowledge. Nearly every
sophomore medical student has himself performed, or seen performed
such “experiments” as are therein described. The claims of novelty
evidently are confined to the assertion that the preparation is able to
“resist oxidation or deterioration”; that it is free from “poisonous
and irritable chemical substances”; that it “may be administered orally
to produce the desired physiological action.” etc., etc. Not the
slightest hint is given as to how any person can substantiate these
claims. As a matter of fact, the investigation of Professor Carlson
and his co-workers has shown that a preparation having the properties
claimed cannot be made by the process described in this patent. Any
one familiar with the subject could have demonstrated readily that the
applicant was withholding information concerning essential features of
his process, assuming that he had any information on the subject (which
he probably did not have) and would have advised against the issuance
of the Beveridge patent.--(_From The Journal A. M. A., Jan. 12, 1918_.)
SURGODINE
Report of the Council on Pharmacy and Chemistry
The following report submitted by a referee was adopted by the Council
and authorized for publication.
W. A. Puckner, Secretary.
Surgodine (Sharp and Dohme, Baltimore, Md.), according to an
advertising pamphlet, is a solution of 2-1/4 per cent. of iodin in
alcohol, containing no alkaline iodid, but miscible with water in all
proportions. The A. M. A. Chemical Laboratory reports that Surgodine
is an alcoholic liquid (containing 91.8 per cent. alcohol by volume)
containing free iodin, combined iodin and free acid, probably hydrogen
iodid (hydriodic acid). Quantitative estimations gave 2.51 gm. free
iodin per 100 c.c. and 1.78 gm. combined iodin (the greater part
apparently was present as hydrogen iodid).
It is therefore similar to several other iodin preparations already
considered by the Council. Like these, it is essentially similar to
the official tincture of iodin, except that it is considerably weaker,
and instead of potassium iodid it presumably contains hydrogen iodid
and probably ethyl iodid to render the iodin water-soluble. Its
composition, however, is secret.
There would be no objection to the use of ethyl iodid or hydrogen
iodid, except perhaps the acidity of the latter, as a solvent agent
rather than of potassium iodid. But neither is there any important
advantage, and these preparations would have to be considered as
unessential modifications of official preparations, and therefore
ineligible for New and Nonofficial Remedies.
The attempt to make these modifications commercially profitable,
however, seems inevitably to lead to exaggerations and misstatements.
In an advertising pamphlet the following claims for Surgodine are
unsupported by any evidence:
“But from the surgical viewpoint the addition of this potassium
salt is most objectionable because when such solutions as the
official tincture are used locally in the antiseptic treatment of
open and often infected wounds the Potassium Iodide acts as an
irritant to the wound and therefore produces a localized irritation
which is not only objectionable from the surgical standpoint but
also materially lessens the antiseptic power of the Iodine itself.”
“It has been demonstrated repeatedly that Iodine without the
admixture of any alkaline iodide is much more efficient as a
surgical antiseptic than any iodine solution that contains such an
addition.”
“Iodine does not produce ‘iodism’ as quickly as the alkaline
iodides do because it is eliminated more quickly and more perfectly
than the alkaline iodides.”
The next statement intimates that iodin taken by mouth enters the
intestinal tract unchanged and is there free to combine with various
gases:
“Iodine in the presence of phosphorated or sulphurated gases in the
gastro-intestinal tract unites with their hydrogen and thus breaks
up these noxious compounds.”
This is certainly untrue at least for ordinary doses.
It is recommended that Surgodine be held inadmissible to New and
Nonofficial Remedies because its composition is secret (Rule 1);
because the therapeutic claims made for it are exaggerated and
unwarranted (Rule 6); and because it is an unessential modification of
the official tincture of iodin (Rule 10).
[Editorial Comment.--Surgodine is a good illustration of the economic
waste inseparable from most proprietary medicines. A hospital
pharmacist writes that whereas his hospital obtains tincture of iodin
at less than 82 cents a pint, Surgodine costs $2.13 a pint. This means
that while the free-iodin strength of Surgodine is only about one-third
that of the official tincture, its price is between two and three times
as high.]--(_From The Journal A. M. A., Jan. 26, 1918_)
MEDEOL SUPPOSITORIES
Report of the Council on Pharmacy and Chemistry
The following report on Medeol Suppositories has been adopted by the
Council, and its publication authorized.
W. A. Puckner, Secretary.
“Medeol Suppositories” (Medeol Company, Inc., New York) appear to be
an imitation of “Anusol Suppositories” which, in 1907, were found to
be inadmissible to New and Nonofficial Remedies. A comparison of the
composition and of the claims made for the two preparations will be of
interest in the present consideration of Medeol Suppositories:
ANUSOL SUPPOSITORIES (1909) MEDEOL SUPPOSITORIES (1917)
Anusoli 7.5 Medeol 0.25
Zinc oxid 6.0 Zinc oxid 0.5
Balsam Peru 1.5 Acid. tannic 0.15
Ol. theobrom. 19.0 Bals. Peru 0.16
Ungt. cerat. 2.5 Cocoa butter and wax _q. s._
for 12 suppositories. for 1 suppository.
“Anusol” was formerly said to be bismuth iodoresorcinsulphonate. The
A. M. A. Chemical Laboratory published a report in 1909 showing that
the suppositories contained only 1 per cent. of the iodin declared
in the “formula,” and were greatly deficient in bismuth and sulphur.
After the publication of the report the American agents for the product
disclaimed that “Anusol” was a definite chemical compound. Today Anusol
Suppositories are said to contain unstated amounts of the indefinite
“bismuth oxyiodid and resorcinsulphonate.”
“Medeol” is said to be “resorcinated iodo bismuth,” but no information
is vouchsafed as to the character or composition of the ingredient. The
therapeutic claims made for the two preparations are similar, as the
following, taken from circulars, show:
ANUSOL SUPPOSITORIES
An innocuous, non-irritant remedy for anal, rectal and vaginal
inflammatory affections, especially for HEMORRHOIDS!
The local medicinal treatment of hemorrhoidal and other
inflammatory ano-rectal conditions has always been unsatisfactory.
The usual media cannot be applied in effective concentration
without producing intense inflammatory reactions; they are either
ineffective or intolerable....
Anusol suppositories are absolutely free from narcotic, caustic or
other injurious ingredients and may unhesitatingly be used by both
sexes, at any age and under all conditions.
MEDEOL SUPPOSITORIES
An innocuous, Non-irritant, Efficient Antiphlogistic for use in
inflammatory diseases of the rectum, anus and vagina especially in
HEMORRHOIDS.
Hitherto most of the local remedies used in these conditions
have either been too irritating to be employed in sufficient
concentration to be efficient or they have lacked efficiency per
se....
Medeol suppositories do not contain any narcotic or any caustic or
other constituent having violent action; their blandness permits of
their use in either sex and at all ages.
The claims made for these preparations--as for instance “that surgical
treatment ... should rarely be undertaken until Medeol Suppositories
have been given a thorough trial”--are misleading in that they create
the inference that the limitations in the palliative treatment of piles
have been overcome. It is altogether untrue that these mixtures can be
expected to “relieve the most obstinate cases,” as stated in a Medeol
circular. This, from an Anusol circular, is equally misleading:
“If dietetic and other requirements are complied with, even the
most obstinate chronic cases will frequently readily yield to
treatment with Anusol Suppositories.”
The Council declared Medeol Suppositories inadmissible to New and
Nonofficial Remedies because their composition is secret (Rules 1 and
2); because unwarranted therapeutic claims are made for these (Rule 6);
because the name is objectionable (Rule 8), and because the combination
is unscientific (Rule 10).
In those cases of hemorrhoids in which palliative measures may be
expected to enable the patient to avoid surgical interference and
afford relief from attacks, the object should be to secure cleanliness,
to avoid irritation, whether it be by friction or irritating fecal
matter, to reduce inflammation by astringents and, when necessary,
to relieve pain by analgesics. If an antiseptic dusting powder is
desired, boracic acid in impalpable powder with talc may be employed;
if an astringent, finely powdered oxid of zinc may be added; if a
local analgesic is necessary, a little extract of belladonna may be
incorporated with petrolatum or other ointment base. The main reliance,
in any event, should be to effect normal bowel movements by regulating
the diet rather than by the use of purgatives; the use of warm water
to insure cleanliness; the avoidance of irritation, especially that
caused by friction and secretions; a mild astringent to reduce
inflammation.--(_From The Journal A. M. A., March 9, 1918_)
GUAIODINE
Report of the Council on Pharmacy and Chemistry
The following report on Guaiodine, marketed by the Intravenous Products
Company, Denver, has been adopted by the Council and its publication
authorized.
W. A. Puckner, Secretary.
A referee of the Committee on Pharmacology, in submitting to the
Council a report from the A. M. A. Chemical Laboratory on Guaiodine,
advises that the Laboratory’s examination shows that instead of
containing free “colloidal” iodin as claimed, the preparation is
essentially an iodated fatty oil, containing only combined iodin.
Equally misleading, in view of the Laboratory’s findings, are the
implied claims that the antiseptic action of Guaiodine corresponds to
that of free iodin.
Guaiodine is advertised mainly for the treatment of gonorrhea. While
it may be true that the guaiacol contained in Guaiodine has some
beneficial effect, especially when preceded by potassium permanganate
irrigation as advised, the advertised claim that “Guaiodine acts as a
specific for gonorrhea in a majority of cases” is utterly false.
The “case records” offered to establish the therapeutic value of
Guaiodine are in themselves sufficient to condemn the “evidence.” The
following are fair samples:
“The second boy came a day or so later with a slight discharge with
the characteristic burning and itching, and with symptoms of a
beginning gonorrhea, and judging from the source of the infection,
it was believed to be so. Two injections of Guaiodine were given
when the discharge ceased.”
“I have several cases that were completely cured in a very short
time. I note this, that the first dose causes a cessation of the
discharge and the second seems to increase the flow, but the color
is changed. I give three doses, and then use a mild wash, and in
ten days they are well. I am very pleased with this preparation and
very truly believe that it is the best there is to date for the
positive cure of gonorrhea.”
REPORT OF THE CHEMICAL LABORATORY
Guaiodine is manufactured by the Intravenous Products Company, Denver,
Colorado. The “literature” which accompanies the product describes
Guaiodine as:
“... an electro-chemically prepared iodin, suspended in oil,
containing iodin, the same strength as the U. S. P. tincture
of iodin, or 7 per cent., together with a therapeutic dose of
guaiacol.”
The Intravenous Products Company claims that Guaiodine is made by an
“electro-chemical process of preparing colloidal iodine,” discovered
by one E. B. Page, and that by this process the tendency of iodin to
produce iodism has been “overcome.” It is said to be “pre-eminently
an antiseptic and germicide.” Guaiodine is a dark brown, oily liquid
with a specific gravity of 0.9845 at 15.6 C. and an odor suggestive
of guaiacol. Its solubilities were those of a fat. Free iodin was
absent in the recently purchased specimen (traces were present
in an older one). Steam distillation indicated that the product
consisted of volatile and nonvolatile constituents. The volatile
matter was concluded to consist, in the main, of guaiacol or some
guaiacol-like body, and the nonvolatile matter to be an iodized fatty
oil. Quantitative determinations indicated that Guaiodine contained
about 7.25 per cent. of iodin in combination, and that it is composed
approximately of 3 per cent. volatile matter and 97 per cent.
nonvolatile matter. Hence Guaiodine appears to be an iodized fatty oil
to which a small amount of guaiacol or some guaiacol-like substance has
been added.
THE COUNCIL’S ACTION
On the recommendation of the referee, the Council voted that Guaiodine
be declared inadmissible to New and Nonofficial Remedies because of
false statements as to composition and action.--(_From The Journal
A. M. A., April 6, 1918._)
SEVERAL “MIXED” VACCINES NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The “mixed” vaccines which are discussed in the reports that follow
were considered by the Council during the past year because inquiries
had been received in regard to them.
In publishing these reports it is desirable that the attitude of the
Council toward “mixed” vaccines again be stated. In view of the rapid
development of bacterial therapy, the possibility for harm that attends
the use of bacterial vaccines and the skepticism among experienced
clinicians as to the value of vaccines representing a combination of
organisms, the Council has felt that it should scrutinize the claims
for such agents with exceptional care and that there should be admitted
to New and Nonofficial Remedies only those vaccine mixtures for which
there is acceptable evidence to indicate that the use of the particular
mixtures is rational.
In considering the subject the Council has borne in mind the fact that
in many institutions in which cases are studied and the results of
therapeutic measures carefully observed and controlled, vaccines of any
sort are practically never used--certainly here the stock mixed vaccine
has no recognition. Experienced clinicians have generally come to the
conclusion that mixed vaccines have no specific action and that any
effect they may produce is due to a non-specific protein reaction.
As set forth in the reports, in no case was the evidence submitted
by the proprietors sufficient to establish the claims made for the
preparations. Hence none was accepted for New and Nonofficial Remedies.
The preparations that form the basis for the accompanying reports are
only a few of the many that are being made and sold by some biological
houses. Doubtless many of those not dealt with in this report are
equally irrational and sold under claims equally--or probably even
more--unwarranted than those with which the present report deals.
W. A. Puckner, Secretary.
Mixed Vaccines-Abbott
In response to inquiry the Council undertook a consideration of the
following “mixed{”} vaccines sold by the Abbott Laboratories:
_M. Catarrhalis-Combined-Bacterin_, said to contain killed Micrococcus
catarrhalis, Bacillus Friedländer, Pneumococci, Streptococci,
Staphylococcus aureus and Staphylococcus albus.
_B. Coli-Combined-Bacterin_, said to contain killed Streptococcus
viridans, Streptococcus hemolyticus and Bacillus coli.
_Pertussis-Combined-Bacterin_, said to contain killed Bacillus
pertussis, Pneumococci, Streptococci, Staphylococcus albus,
Staphylococcus aureus and Micrococcus catarrhalis.
_Streptococcus-Rheumaticus-Combined-Bacterin_, said to contain killed
“Streptococci (Rheumaticus, Viridans, etc.)” and Pneumococci.
_Streptococcus-Viridans-Combined-Bacterin_, said to contain killed
Streptococcus viridans, Streptococcus hemolyticus, Pneumococcus and
Staphylococcus albus.
The Abbott Laboratories were asked to assist in the investigation of
these products and to submit evidence to establish their eligibility
for admission to New and Nonofficial Remedies. The manufacturer was
informed that the Council accepts “mixed” vaccines or bacterins,
provided the usefulness of these products is established by acceptable
clinical evidence, and references to the literature bearing on the
value of the preparations were requested.
The Abbott Laboratories submitted specimens of the products, the
advertising matter therefor and a considerable list of references to
current literature; all of which was transmitted to the Committee on
Serums and Vaccines for consideration. In due time a referee of the
committee submitted the following report:
THE COMMITTEE’S REPORT
The referee has studied the literature covered by the references
submitted. In general the articles are favorable to the use of
vaccines, though many of these papers do not consider “mixed”
vaccines; indeed, a number of the articles do not discuss treatment
at all, but are devoted entirely to the consideration of etiology
of the disease. Many of the papers are by those who are obviously
overenthusiastic on the subject of the use of biologic preparations.
One paper--not included in the references submitted by the Abbott
Laboratories--records an alarming reaction following a dose of mixed
vaccine; no claim is made that improvement followed.
The following comments on the submitted references are offered:
_M. Catarrhalis-Combined-Bacterin._--Only four of the nine references
given deal with the therapeutic use of the vaccine. The reported
results in general were favorable, but sometimes in the discussion
evoked by certain of the papers, views the reverse of those expressed
by the author were brought forward. The enthusiasm of one writer is
shown in his statement that following the use of vaccine in cases of
carbuncle complicating diabetes the sugar in the urine disappeared
or was reduced. One observer, who reports excellent results in nasal
pharyngeal catarrh, speaks of certain vaccines as “bulk goods,” while
another considers “----’s No. 7” as the proper thing. It is evident
that the reports are not based on careful, scientific data, or such
unscientific definition of the product employed would not be used.
_B. Coli-Combined-Bacterin._--In the references cited in support of
this preparation the following general statements are noted: One
enthusiastic writer says, “It must be recognized that we have no
satisfactory explanation of the action of vaccines, and their use
at present is empirical.” One author dwelt on the superiority of
autogenous vaccines but admits that occasionally stock vaccines are
indicated. One vaccine therapist in concluding an article states, “It
is simply impossible to practice modern urology without our modern
biologic products.” Yet it is a well-known fact that many successful
and capable genito-urinary surgeons avoid the use of vaccines, mixed or
simple.
_Pertussis-Combined-Bacterin._--These reports are uniformly favorable,
but are not controlled and their value is not to be compared with
a recent report from the New York City Department of Health which
indicates that the vaccine is practically valueless. It is noted,
further, that one of the articles cited which dealt rather fully with
the treatment of pertussis did not mention vaccines.
_Streptococcus-Rheumaticus-Combined-Bacterin._--The references cited
in support of the preparations by the manufacturer give no support
whatever for the use of mixed stock vaccines. The first reference deals
with the relation of Streptococcus viridans to arthritis deformans and
endocarditis and reports the following cases:
_Case 1._--Vaccine case--improvement after eight months.
_Case 2._--Slight improvement following use of vaccine.
_Case 3._--Slight improvement following use of vaccine.
_Case 4._--Marked improvement.
_Case 5._--Prompt improvement.
_Case 6._--Vaccine not mentioned.
_Case 7._--Vaccine followed by slight improvement.
In each of the cases other methods of treatment were used. The paper
shows the etiologic relation of Streptococcus viridans rather than
the value of vaccines. There is no indication that stock vaccines
were used, though the paper is not clear on this point. The second
paper deals with the application of vaccine therapy in the treatment
of arthritis. This paper is by a man who is avowedly an enthusiast on
vaccine therapy. The indications are that he generally used a mixed
autogenous vaccine, but the reports of cases are not always clear.
This writer apparently makes no serious attempt at the classification
of the joint conditions he treats. The third reference is a purely
experimental study and has no bearing on the use of vaccines in
treatment. The fourth article was admitted by the manufacturer to be
“negative as regards evidence.” The fifth reference specifically states
that “the vaccine must be autogenous.” The sixth reference deals with
the experimental production of appendicitis by the use of diplococci,
and has not the most remote bearing on the use of vaccines in the
treatment of rheumatism.
_Streptococcus-Viridans-Combined-Bacterin._--The article which bears
evidence of more care than the others admits that we are not in
position to state the value of vaccines in pyorrhea but the author
believes they may have value supplementary to local treatment.
It is not surprising that a large number of favorable reports can
be accumulated when we appreciate how promptly men report what they
consider to be their successes and how commonly they leave their
failures unrecorded. Bearing in mind the fact that these stock mixed
vaccines, though before the profession for many years, have not
been used, or continued in use, in hospitals where work is rigidly
controlled and that they are used practically not at all in the large
government hospital service, a candid critic must hold that there is
no substantial evidence in favor of the therapeutic use of a mixed
vaccine, certainly not for stock “goods” and that probably there is but
a limited field for the employment of autogenous vaccines.
The referee calls attention to a shift in the advertising matter on
vaccines--the tendency to recommend vaccines to be used in conjunction
with drugs. A heading in the Abbott booklet reads, “The Biologics Do
Not Replace Drugs”; and the paragraph speaks of serums and bacterins as
“new tools, supplemental to those we already have, but not replacing
them.” ... “We need them both.”
The referee recommends that the several mixed vaccines discussed in
this report be not accepted on the grounds that satisfactory evidence
of their value is wanting.
Having been endorsed by the Committee on Serums
and Vaccines the Council adopted the report and
declared M. Catarrhalis-Combined-Bacterin, B.
Coli-Combined-Bacterin, Pertussis-Combined-Bacterin,
Streptococcus-Rheumaticus-Combined-Bacterin and
Streptococcus-Viridans-Combined-Bacterin ineligible for admission to
New and Nonofficial Remedies.
Catarrhal Vaccine Combined-Lilly and Influenza Mixed Vaccine-Lilly
Because of inquiry received, the Council requested Eli Lilly and
Company to aid in determining the acceptability of the following
products for New and Nonofficial Remedies: “Catarrhal Vaccine
Combined,” said to contain killed cultures of the Bacillus of
Friedländer, Micrococcus catarrhalis, Staphylococcus aureus and
albus, Pneumococcus and Streptococcus; “Influenza Mixed Vaccine,”
said to contain killed cultures of Staphylococcus albus and aureus,
Streptococcus, Pneumococcus, Micrococcus catarrhalis and Bacillus
influenzae.
Lilly and Company sent the circulars, etc., used in advertising these
products. A circular for “Catarrhal Vaccine Combined” contained the
following claim:
“Catarrhal Vaccine has been especially useful in many respiratory
infections, including bronchitis, pharyngitis, rhinitis, chronic
catarrh and in the mixed infections of pulmonary tuberculosis.”
A circular for “Influenza Mixed Vaccine” contained the following:
“The vaccine is useful in the treatment of influenza and ordinary
colds, and in any infection in which the Bacillus influenzae is the
causative agent.”
An advertising pamphlet contained the following:
“Catarrh, Acute and Chronic; Colds, Influenza.--The micro-organisms
capable of producing catarrhal conditions of the nose and pharynx
and most commonly isolated are B. Friedländer, M. catarrhalis,
staphylococcus, pneumococcus (in infections beginning in the
larynx), _B. influenza_ and streptococcus. These organisms are
found normally in the respiratory passages and acquire virulence
only when resistance has been lowered through overwork, exposure to
cold, etc.
“The results following the use of Catarrhal Vaccine Combined
(in the non-epidemic forms) and influenza Mixed Vaccine (in the
epidemic types) have been very satisfactory, due to the great
vascularity of the tissues. Acute attacks are aborted altogether
or shortened in duration and the danger of complications greatly
minimized.”
No evidence was submitted which warrants the preceding claims nor
is the Council aware of any reliable testimony to indicate that the
administration of the mixture here discussed is warranted or desirable.
On the recommendation of the Committee on Serums and Vaccines the
Council voted that “Catarrhal Vaccine Combined-Lilly” and “Influenza
Mixed Vaccine-Lilly” be not included in New and Nonofficial Remedies
because satisfactory evidence of their value is wanting.
Influenza Serobacterin Mixed-Mulford
Because of inquiry received, the Council took up the consideration
of “Influenza Serobacterin Mixed-Mulford,” and requested the Mulford
Company to present evidence to establish the admissibility of the
preparation to New and Nonofficial Remedies. The Mulford Company sent
specimens of the serobacterin in question, an advertising circular and
a letter by the director of its Biologic Laboratories.
According to the label on the package, the preparation is made from
the following organisms: Bacillus influenzae, Staphylococcus aureus,
Staphylococcus albus, Streptococcus, Pneumococcus and Micrococcus
catarrhalis (group). This mixture is recommended by the manufacturer:
“For the prophylaxis and Treatment of Common Colds, Mixed
Infections of the Respiratory Mucous Membranes, Acute and Chronic
Catarrhal Conditions of the Nose, Throat and Respiratory Passages.”
No evidence is submitted for this recommendation except that in “colds
and bronchitis and the other common infections of the upper respiratory
passages ... five or six bacteria are very commonly present--two or
more of them are nearly always present ...” and the letter by the
director of the Mulford Biologic Laboratories expressing the belief
that in his own case the use of the mixed vaccine has aborted or
prevented colds.
As regards the use of this complex biologic preparation:
First, the cause of common colds is, at the present time, quite
unknown. One of the most striking things is that at the beginning of
a cold the organisms to be cultivated from the nasal mucous membrane
are very few in number and there is no uniformity in the type of
organism found. If someone of the well-known organisms (Streptococcus,
Staphylococcus, Pneumococcus, Micrococcus Catarrhalis, Influenza
Bacillus, etc.) were responsible, we should expect to find one of them
preponderating and in overwhelming numbers. This is far from the case.
After the duration of the cold for a day or two with the increased
production of mucus and apparently with the infection of a mucous
membrane whose powers of resistance have been greatly lowered, bacteria
of all kinds are to be found in immense numbers. There is considerable
reason for believing that an ultramicroscopic organism is responsible
for this condition (See Foster, _Journal of Infectious Diseases_
=21=:451 [Nov.] 1917).
Second, there is no acceptable clinical evidence that vaccination with
the influenza bacillus, the Streptococcus, the Pneumococcus or the
Micrococcus Catarrhalis will influence the course of an infection due
to one or the other of these organisms. It has been repeatedly found
that a staphylococcus vaccine is of a certain degree of value when the
infection with the staphylococcus is localized, but it is well known
that general systemic infections with the staphylococcus are not at all
benefited.
Third, the letter submitted as evidence by the Mulford Company is not
convincing. The Council is not prepared to accept evidence of this sort
unless it is in volume large enough to justify a definite conclusion.
Holding that there is no evidence for the value of this mixture, the
Council declared “Influenza Serobacterin Mixed-Mulford” inadmissible to
New and Nonofficial Remedies because its use is illogical.
Sherman’s Mixed Vaccine No. 40
Because of inquiry received the Council decided to consider this
preparation and requested the manufacturer, G. H. Sherman, Detroit,
Mich., to submit evidence in support of the claims made for it.
This vaccine is said to be made from killed cultures of Streptococcus,
Pneumococcus, Micrococcus catarrhalis, Staphylococcus aureus, and
Staphylococcus albus. In the printed matter sent out by G. H. Sherman
this vaccine is recommended for hay-fever, in which it is stated that
some of the symptoms are due to bacterial invasion of the respiratory
mucosa; for tonsillitis, both as a remedy and as a prophylactic against
rheumatic and other sequelae; for “throat infections”; for rhinitis
with the claims that acute coryza can be aborted within twenty-four
hours; for pneumonia in which it is advised for all stages; for
laryngitis, for bronchitis, and for asthma.
No acceptable evidence was submitted as to the value of the product in
the treatment of any of the foregoing conditions. In view of what is
known about non-specific reactions, it seems likely that any influence
which this vaccine may have on the diverse conditions enumerated by
the manufacturer, is due to this, rather than to the combination of
organisms used in its preparation.
On the recommendation of the Committee on Serums and Vaccines, the
Council declared “Sherman’s Mixed Vaccine No. 40” ineligible to New
and Nonofficial Remedies because the therapeutic claims made for it
are unwarranted (Rule 6) and because the combination, in view of
its complexity, is irrational and detrimental to sound therapy (Rule
10).--(_From The Journal A. M. A., June 23, 1918._)
OPHTHALMOL-LINDEMANN
Report of the Council on Pharmacy and Chemistry
Ophthalmol-Lindemann was taken up for consideration by the Council
because of inquiries received. The following report, declaring
Ophthalmol inadmissible to New and Nonofficial Remedies, was adopted by
the Council and its publication authorized.
W. A. Puckner, Secretary.
Ophthalmol-Lindemann (Innis, Speiden and Co., New York) is advertised
as a treatment for eye diseases by “hyperemia.” The circular
advertising the product is written somewhat in the style of “patent
medicine” advertisements. It contains testimonials of dubious value.
The principle underlying the use of Ophthalmol is that employed
to a considerable extent by ophthalmologists, through the use of
ethylmorphine (“dionin”), etc., viz., the production of conjunctival
irritation in inflammatory eye diseases. Ophthalmol is, therefore,
merely a special agent for the production of such ophthalmic irritation.
The advertising circular contains no evidence that Ophthalmol is in any
respect superior to the established agents for producing conjunctival
hyperemia. On the other hand, there are obvious objections to the
use in the eye of a substance of unknown and apparently indefinite
composition and uncertain activity. Ophthalmol is said to be an oily
solution of “glandular extract of the fish Cobitis Fossilis.” _Cobitis
fossilis_ is a small fish said to be common in Germany. According to
Kochs, who analyzed Ophthalmol (_Arb. a. d. Pharm. Inst. d. Univ.
Berl._, =4=:140, 1907), this fish is popularly believed to predict
weather, but medical virtues are not ascribed to it. This “fishy”
extract is indefinite, to say the least.
The activity of the preparation is described by the manufacturer thus:
“It seems probable that the typical action of Ophthalmol is due to
certain organic acids which may have formed during manufacture through
the decomposition of protein bodies contained in the crude material.”
The profession is not told whether this important decomposition is,
or, in fact, can be controlled so as to produce a material of uniform
activity.
Kochs concluded from his analysis that Ophthalmol had the properties
of rancid olive oil containing about 6 to 7 per cent. mineral oil. The
oil contained no nitrogen, left no ash on ignition and though traces of
iodin were claimed to be present, no iodin could be found.
It is recommended that Ophthalmol be rejected first, because the use
in the eye of an irritant of secret composition and uncertain activity
is unscientific and against the interest of public health; second,
because Ophthalmol is of secret composition (the composition claimed
being practically meaningless), and, third, because no evidence has
been submitted to substantiate its claimed superiority over established
methods of treatment. The Council declared Ophthalmol inadmissible to
New and Nonofficial Remedies.--(_From The Journal A. M. A., July 6,
1918._)
SILVOL INELIGIBLE FOR N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report on Silvol (Parke, Davis & Company) was adopted by
the Council and its publication authorized.
W. A. Puckner, Secretary.
The Council took up the consideration of Silvol (Parke, Davis &
Company) because of inquiries received. The following report was
submitted by the referee in charge of silver preparations:
Silvol (Parke, Davis & Company) is a silver-protein preparation of the
Argyrol type. Like Argyrol, it is said to contain about 20 per cent.
of silver. The referee finds that, like Argyrol, it is nonirritant to
the nasal mucosa in a 10 per cent. solution; does not precipitate with
chlorid; dissolves in water readily; a 25 per cent. solution has a high
specific gravity (Silvol, 1.137 at 20 C.; Argyrol, 1.147 at 20 C.), and
is not very viscid (viscosity, 1.25). A 1:1,000 solution of Silvol is
clear and about 50 per cent. deeper in color than a solution of Argyrol
of the same strength.
Silvol differs from Argyrol mainly in that its solutions yield a fine
precipitate with egg albumin (under suitable conditions), while Argyrol
is nonprecipitant; and in that Silvol solutions are not so effectively
decolorized by Lloyd’s reagent.
The manufacturers did not reply to an inquiry with regard to the
basis for the claims made for Silvol (see Appendix). The referee was
therefore obliged to deduce these claims from the firm’s advertising
matter. About the same claims are made for the local use of Silvol as
are generally made for Argyrol. These may be accepted without detailed
evidence in view of the similarity of the two preparations.
Its usefulness, as suggested in the advertising, when given by mouth
“in the treatment of acute or chronic gastritis, gastric ulcer, or
gastro-enteritis,” or the efficacy of very dilute solutions (0.2 per
cent.) against dysentery, etc., is doubtful and requires substantiation
by evidence. The claims that Silvol is astringent, though nonirritant
and noncoagulant, that it is a “powerful germicide” or even that it
is a “powerful antiseptic,” and that it may be used with advantage
wherever “a silver salt is indicated,” need substantiation. There is no
proof of the assertions that Silvol is “the most efficacious of silver
salts”; “the most efficient antiseptic,” and “the most remarkable
organic silver compound ...”
As the manufacturers have not presented any evidence for their highly
improbable claims, and as they have not signified any intention of
making their claims agree with substantiated facts, it is recommended
that Silvol be declared inadmissible to New and Nonofficial Remedies.
The Council adopted the report of its referee and authorized its
publication.
APPENDIX
The following letter from the Secretary of the Council was sent to
Parke, Davis & Company, March 20, 1917. No reply to it has been
received:
The referee of the Council who is conducting an investigation of
silver preparations asked me to inquire if you are willing to
submit your evidence for the following claims which are made in
your circulars for Silvol:
1. How it is possible for the solution to be astringent, and at the
same time nonirritant and noncoagulant?
2. That intestinal irrigation with a Silvol solution containing
10 to 15 grains to the pint is sufficiently bactericidal to “be
used in the abortive treatment of such infectious processes as
dysentery, cholera infantum, and colitis.”
3. What evidence have you as to the degree of antiseptic and
germicidal power of Silvol solutions?
4. What evidence have you as to the degree of antiseptic and
germicidal power of 5 per cent. Silvol Ointment?
A reply to the above questions and any other information in regard
to Silvol will receive careful consideration.--(_From The Journal
A. M. A., July 13, 1918._)
KATHARMON
Report of the Council on Pharmacy and Chemistry
Following inquiries, the Council took up “Katharmon” for consideration
and authorized publication of the following report.
W. A. Puckner, Secretary.
The Katharmon Chemical Company of St. Louis in advertising its
Katharmon appeals especially to a profession whose members, should
they live up to their ethical code, could not prescribe it.[124] In
1893 (when the publication of “a formula” for proprietary preparations
was thought to satisfy the requirements of scientific medicine) an
advertisement in The Journal of the American Medical Association gave
the following “formula” for Katharmon:
[124] “... it is equally unethical to prescribe or dispense secret
medicines or other secret remedial agents,...” Sec. 6, Art. I, Chapter
II, _Principles of Medical Ethics_.
“Hydrastis Canadensis, Phytolacca Decandra, Acid Salicylous C. P.
(from Oil of Wintergreen), Acid Boric C. P., Mentha Arvensis,
Thymus Vulgaris, Dist. Ext. Hamamelis Virg. Conc.”
In 1907 an advertisement in the Kansas City _Medical Index-Lancet_
declared that:
“Katharmon represents in chemical combination the active principles
of Hydrastis Canadensis, Gaultheria Procumbens, Hamamelis
Virginica, Phytolacca Decandra, Mentha Arvensis, Thymus Vulgaris,
with two grains C. P. Boric Acid to each fluid drachm.”
Now the advertisements which appear in some medical journals state:
“KATHARMON represents in combination Hydrastis Canadensis, Thymus
Vulgaris, Mentha Arvensis, Phytolacca Decandra, 10-1/2 grains Acid
Borosalicylic, 24 grains Sodium Pyroborate to each fluid ounce of
Pure Distilled Extract of Witch Hazel.”
A comparison of these so-called formulas shows that they have not only
varied from time to time, but that in no instance was a quantitative
statement with regard to all the asserted ingredients given.
The Chemical Laboratory of the A. M. A. reports: Katharmon has an
alkaline reaction and therefore cannot contain boric acid, salicylic
acid or “borosalicylic acid” (the latter is unknown to medical
literature except as loosely applied to a simple mixture of boric and
salicylic acids). The solution gives tests for sodium, borate, and
salicylate and therefore probably contains sodium borate and sodium
salicylate. Examined by the methods used for the determination of
hydrastin in goldenseal preparations, a residue giving only a faint
test for alkaloid was obtained; if present at all, hydrastis canadensis
(goldenseal) is there only in very small amounts.
A circular wrapped with the trade package of Katharmon contained the
following, palpably unwarranted, claims:
“INTERNALLY it is very useful in acute indigestion, Gastric
Catarrh, Diarrhoea and Cholera Infantum.”
“... it has demonstrated its remarkable curative effects, not only
in preventing unhealthy conditions of fresh wounds, but also in
correcting the decaying of putrefactive processes peculiar to the
body under certain circumstances. It has, further, a remarkable
efficacy in surface inflammations, whether produced by accident
or disease, and is an indispensable remedy in the affections of
the mucous membranes of the nose, mouth, stomach, bowels, vagina,
uterus, urethra, bladder and rectum.”
Katharmon is in conflict with Rules 1 and 4 of the Council on Pharmacy
and Chemistry because of its indefinite and secret composition and
the method of advertising it indirectly to the public; it is in
conflict with Rules 10, 6 and 8, in that it is an irrational shotgun
mixture sold under unwarranted therapeutic claims and under a name
nondescriptive of its composition.--(_From The Journal A. M. A., Aug.
10, 1918._)
IODINIZED EMULSION (SCOTT) AND CREOSOTONIC (SCOTT)
Report of the Council on Pharmacy and Chemistry
“Iodinized Emulsion (Scott)” and “Creosotonic (Scott)” are proprietary
preparations of the Dawson Pharmacal Company, Dawson Springs, Ky. The
latter preparation used to be known as “Iodinized Emulsion (Scott) with
Hypophosphites, Guaiacol and Creosote.” In 1907 these preparations were
considered by the Council and found inadmissible to New and Nonofficial
Remedies. Examination of the preparations having been again requested,
the Council considered them anew because the composition and claims
had been changed somewhat and because at the previous consideration no
report was published.
The reports which appear below were sent to the Dawson Pharmacal
Company for comment before publication. In reply the company offered to
revise its claims for the preparations. The Council replied that the
report sent explained that both preparations are irrational mixtures,
and hence a revision of the claims would not make them eligible for New
and Nonofficial Remedies. It advised that publication of the report
would be withheld sixty days and that it would be revised if new
information or evidence was submitted permitting such revision. After
expiration of the stipulated postponement, the Dawson Pharmacal Company
wrote that no new advertising matter had been prepared, but that the
old circulars were not being sent out.
As these irrational preparations were still sold and advertised to the
medical profession and presumably used by some physicians, the Council
directed publication of its report with this explanation.
W. A. Puckner, Secretary.
Iodinized Emulsion (Scott)
The label for Iodinized Emulsion (Scott) declares:
“Each fluidram contains: Alcohol, m. 4-3/4; Rectified Ol. of
Turpentine, m. 3-1/2; Iodin, gr. 1/8; Phenol, gr. 1/2; Glycerine
and Elixir Lactated Pepsin with Aromatic Oils in the form of a
perfect emulsion.”
A circular which gives what is asserted to be the composition of
Iodinized Emulsion, declares that, among other ingredients, each
fluidram contains “one and three quarters m. Tincture of Iodine.”
Both the statement on the label that the preparation contains “iodin”
and the one in the circular that tincture of iodin is present in the
product are incorrect, for the A. M. A. Chemical Laboratory reports
that no free iodin could be detected in the preparation, and that it
responded to tests for iodid instead.
An advertising circular for Iodinized Emulsion (Scott) makes
unwarranted claims for the therapeutic properties of the constituents.
For example:
“... the great usefulness of Turpentine in diseases, especially of
the Intestinal Infection, such as the Meteorism and Tympanites of
Typhoid.”
And this absurdity:
“... where Turpentine, Carbolic Acid or Iodine or even Pepsin is
indicated, that it will give satisfaction in each and every case.”
Iodinized Emulsion (Scott) is not a “pharmaceutical triumph”; it is an
irrational mixture--a reminder of a decadent polypharmacy--sold under
misleading and unwarranted claims. It is inadmissible to New and
Nonofficial Remedies for conflict with Rules 1, 6, 8 and 10.
Creosotonic (Scott)
Creosotonic (Scott), advertised as a “reconstructive tonic” for the
tuberculous, according to the label, contains in each fluidram:
“Alcohol, m. 2-1/2; Creosote and Guaiacol sulphonates of each,
gr. 1; Compound Hypophosphites, gr. 1 (including Quinine
Hypophosphites, gr. 1/36 and Strychnine Hypophosphites, gr. 1/256),
with Iodinized Emulsion (Scott) m. 30.”
As in the case of Iodinized Emulsion (Scott), the advertising makes
exaggerated therapeutic claims for the individual constituents of the
preparation and for the heterogeneous mixture of guaiacol and creosote
sulphonates, hypophosphites, quinin, strychnin, turpentine, phenol,
iodin, “lactated pepsin,” etc. Thus, while it is well established that
in guaiacol sulphonate and creosote sulphonate the phenolic constituent
is bound so firmly that, when administered, but very little is split
off in the organism, yet the advertising claims “that the system can
be saturated in a shorter time and with smaller doses of creosote and
guaiacol sulphonates than with any other form of these drugs” and that
(on the false premise that the guaiacol and creosote from these drugs
will permeate the tissues of the lungs) “they help to clear up the
local infection and thus aid in returning to normal the diseased mucous
membrane.”
In the advertising pamphlet, following a discussion of the effect of
climate and food in the treatment of the tuberculous, we read:
“While admitting the great importance of the foregoing points, we
are firmly of the opinion that proper medication is a great aid in
the treatment of pulmonary tuberculosis, and, with this in view, we
offer to the profession Creosotonic (Scott) believing that in it we
have a superior preparation for this purpose.”
This is unwarranted. Of course suitable medication to meet special
conditions is proper in the treatment of tuberculosis, but the routine
administration of a complex and irrational mixture such as Creosotonic
(Scott) is bound to cause inattention to the prime requisites for the
proper treatment of the tuberculous--hygienic surroundings and good
food.
Creosotonic (Scott) is an irrational mixture, sold under misleading and
unwarranted claims. It is inadmissible to New and Nonofficial Remedies
for conflict with Rules 1, 6, 8 and 10.--(_From The Journal A. M. A.,
Aug. 24, 1918._)
CAMPETRODIN AND CAMPETRODIN NO. 2
Report of the Council on Pharmacy and Chemistry
The following report on Campetrodin and Campetrodin No. 2 has been
adopted by the Council and its publication authorized.
W. A. Puckner, Secretary.
The following report of the A. M. A. Chemical Laboratory on
“Campetrodin” and “Campetrodin No. 2,” sold by the A. H. Robins
Company, Richmond, Va., was submitted to the Council by a referee of
the Committee on Pharmacology:
Campetrodin and Campetrodin No. 2, Double Strength, are called “ethical
medicinal specialties” by the A. H. Robins Company, Richmond, Va.,
which sells them. An advertisement in the _Maryland Medical Journal_
(December, 1917) contains the following claim for composition:
“CAMPETRODIN (Made in Two Strengths of Iodine). This preparation is
an Oleaginous Solution of Iodine in Camphor.”
A booklet describing the “specialties” of the Robins Company contains
the following in reference to Campetrodin: “Composition: Camphor,
Iodine Element, Oleaginous Solvent.” From this it appears that the
preparations are claimed to contain elementary (free) iodine in an
“oleaginous solvent.” Since free iodin, as is well known, readily
combines with fats, it was decided to determine the form in which the
iodin was present in these preparations. The examination demonstrated
that both preparations contained but a trace of free iodin. On steam
distillation there was obtained from both preparations a distillate
amounting to about 35 per cent. by volume which had an odor strongly
suggestive of turpentine, while the residue contained the iodin and had
the characteristics of an iodized fatty oil.
Quantitative determinations indicated that Campetrodin contained
approximately 0.03 per cent. of free iodin and 1.3 per cent. of iodin
in combination with the fatty oil. Campetrodin No. 2, Double Strength,
contained approximately 0.03 per cent. free iodin and 2 per cent. of
iodin in combination with the fatty oil.
Thus, contrary to the published statements, Campetrodin is _not_ a
preparation of free (elementary) iodin and Campetrodin No. 2, Double
Strength, does _not_ contain twice as much iodin as Campetrodin.
The report of the Chemical Laboratory shows that the statements made
in regard to the composition of Campetrodin and Campetrodin No. 2
are incomplete in some respects and false in others. In view of the
Laboratory’s findings it appears superfluous to inquire into the
therapeutic claims made for the preparations: It is evident, however,
that a solution containing practically no free iodin is not, as claimed
by the Robins Company, “adapted for use wherever ... iodin is indicated
externally....”
It is recommended that Campetrodin and Campetrodin No. 2 be declared
inadmissible to New and Nonofficial Remedies because of false
statements as to chemical composition and therapeutic action,
constituting conflicts with Rules 1 and 6.
The Council adopted the recommendation of the referee and authorized
publication of this report.--(_From The Journal A. M. A., Sept. 21,
1918._)
CARMINZYM
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following which explains
why Carminzym was not accepted for New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Carminzym is a tablet sold by Fairchild Bros. and Foster, New York.
Each tablet contains, according to claims made, approximately 32 mg.
of an extract of pancreas, 50 mg. sodium bicarbonate, 172 mg. prepared
chalk, 1.5 mg. powdered ipecac and “aromatics _q. s._” Without
considering other possible conflicts with its rules, the Council held
the preparation inadmissible to New and Nonofficial Remedies for
conflict with Rule 10 which holds that unscientific or useless articles
are not acceptable products.
The Council holds that complex mixtures of remedial agents are, from
every point of view, inimical to therapeutic progress and therefore to
the public welfare. Such mixtures are especially objectionable because
it is impossible accurately to determine the effects which follow the
simultaneous administration of a number of drugs having dissimilar
actions; because the practice of prescribing such mixtures tends to
discourage careful consideration of the special needs of individual
patients without which there can be no rational drug therapy. On the
contrary, with the use of such mixture therapeutic treatment becomes
haphazard and mere guesswork.
The Council, appreciating that long established customs cannot be
changed at once, has applied Rule 10 concerning the recognition of
mixtures with the greatest leniency compatible with consistency. When
there has been a reasonable doubt concerning the value of a mixture
it has frequently directed that Rule 10 should not apply pending
further clinical trial of such mixture. In no instance has subsequent
experience shown that a strict interpretation of the rule would have
worked hardship or injustice. The Council feels that there is no longer
warrant for the admission of complex mixtures to New and Nonofficial
Remedies or for the retention of any that have been admitted unless
definite evidence of the therapeutic value of such combinations is
available. In accordance with this decision several mixtures now
described in New and Nonofficial Remedies will be omitted at the
expiration of the three year period for which articles are accepted.
Reverting to the Carminzym tablet: When it is desired to obtain the
effects of pancreatic extract by oral administration it must be
administered with a view of preventing its destruction by the gastric
fluid. With this end in view an antacid should be administered to
decrease the acidity of the gastric juice. The amount of alkali may
be supplied in the form of any of the official preparations, but the
amount must be adjusted to the individual patient for the reason that
no two successive patients are likely to have the same degree of
gastric acidity.
Ipecac has a well defined though limited field of usefulness. When it
is used, it should be given with a due regard to the amount needed by
the patient and the frequency of the repetition of the dose. There is
no reason to suppose that any two successive patients will require
ipecac and extract of pancreas in a fixed proportion and with equal
frequency. As a matter of fact, the amount of ipecac in Carminzym is so
small that no definite therapeutic action can be assigned to it and its
use in this combination is purely empirical.
In a word, the employment of mixtures of pancreatic extract, alkalis,
ipecac and carminatives in fixed proportion leads to slipshod treatment
and irrational therapeutics. Carminzym is an irrational mixture the use
of which is detrimental to therapy.
The preceding report was sent to Fairchild Bros. and Foster for comment
in accordance with the Council’s usual procedure. The following reply
was received:
The long established custom of the use of mixtures of remedial
agents rests upon considerations well known and generally accepted.
This is equally true of combinations of drugs of similar and
dissimilar properties. The drugs of these combinations, especially
those of marked therapeutic action, are well known and used by
themselves when indicated.
In fact, dissimilarity of action is a cause of combination, an
essential of synergism.
Drugs classed as similar are by no means alike in action;
laxatives, tonics, carminatives, diuretics are combined with
distinct advantage, economy of dose, enhanced effect, potency not
obtainable with the single drug.
Your sweeping arbitrary conclusions that complex mixtures
of remedial agents are from every point of view inimical to
therapeutic progress is not, it seems to us, sustained by fact and
experience. There is therapeutic progress in the considerate use
and observation of combinations as well as in the use of a single
drug. Indeed, in the production of a synthetic chemical substance
as a therapeutic agent, the combination of potent and dissimilar
elements is worked out to mitigate and correct an objectionable
side effect, and promote desirable action.
As for ourselves, at the very outset in our line of work we quite
voluntarily declared our principles and our intentions as opposed
to incompatible and therefore unstable or inert combinations
of the enzymes; and against the “unnecessary multiplication of
preparations”--see Fairchild’s Hand-Book of the Digestive Ferments.
Is not this after all the crux of the whole matter--does a
combination contain the ingredients stated, does it possess the
demonstrable properties which are to be attributed to it in
consequence of this composition; and if for a certain purpose, is
it well designed therefor?
Carminzym presents certain agents of well known properties, not
in the least of incompatible or antagonistic action, but indeed
especially suitable for the particular purpose designed; its
efficacy not to be measured and judged by theory or opinion as to
the efficiency of a certain dosage of a particular drug by itself.
That the doses as contained are minimal and effective is distinctly
advantageous.
The alkaline carbonates are in Carminzym in stated quantities;
the physician adjusts the dosage to the individual patient and
with obvious evidence of the efficiency of the adjustment. As
we understand it, the employment of alkaline carbonates is not
based on purely chemic considerations--a definite known quantity
of acid of the gastric juice is to be neutralized; the whole
literature and practice dealing with the alkaline carbonates show
them to be accredited with a much wider field of use and repute in
gastro-intestinal disorders.
The pancreatic extract in Carminzym is designed to be diffusible in
the stomach, the tablet is preferable to be crushed in the mouth
before swallowing, and we believe the pancreatic extract to be an
effective constituent as administered in Carminzym.
You comment as follows:
“Ipecac has a well defined though limited field of usefulness.
When it is used it should be given with due regard to the amount
needed by the patient and the frequency of the repetition of the
dose.”
This in a sense may be said of any of the most useful drugs, but not
in the least special degree does it apply to ipecac, which is, on
the contrary, of quite characteristic, peculiar range of therapeutic
properties, useful in varying combinations and in widely varying
proportions and doses according to the purpose for which it is
employed.
Ipecac in well known official alkaline, carminative, laxative
preparations occurs in the “average dose” in the varying quantities
of 1/14, 1/10, 1/8, and 3/16 of a grain.
The ipecac in combination with the other ingredients in Carminzym is
designed for a tablet which shall carry a minimal quantity whilst
capable of adequate remedial action, thus admitting of increase of
dosage or repetition as occasion requires. The quantity of ipecac
was not taken at random, but chosen after long trial and
consideration.
We believe that Carminzym possesses carminative properties in
a superior degree and that, furthermore, in consequence of its
composition it directly stimulates the gland secretions and thus
exerts a beneficial action upon the whole digestive functions.
Carminzym is for use as occasion requires, and this is to be
especially noted. Thus it is not only of direct benefit, but helpful
in promoting systematic therapeutic measures and regimen.
The Council takes the ground that complex mixtures of remedial
agents are so wrong that there is no longer warrant for their
admission into New and Nonofficial Remedies; and that Carminzym
is an irrational mixture.
We hold that certain desirable therapeutic properties may rationally
be attributable to Carminzym; and that these are manifested in
practice.
During the time since the description was sent and the receipt of
the statement of the action of the Council, some ten months,
Carminzym has proved of constantly increasing service.
The statement in the letter of Fairchild Bros. and Foster “The
long established custom of the use of mixtures of remedial agents
rests on considerations well known and generally accepted” might
well be paraphrased to read: The one-time prevalent custom of using
ill-considered combinations of remedial agents has been thoroughly
discredited and is generally abandoned by progressive practitioners.
Such arguments as that “laxatives, tonics, carminatives, diuretics are
combined with distinct advantage” have led to the use of irrational
mixtures such as the compound syrup of hypophosphites and the electuary
of theriaca. The Council is confident that no one who has studied the
causes and treatment of digestive disorders will find occasion to
prescribe at one time all the ingredients stated to be contained in
Carminzym, and certainly not in the fixed proportions present therein.
The comments in the Council’s report concerning ipecac certainly
does apply to all active therapeutic agents. Ipecac was mentioned in
the report because the several constituents of Carminzym were under
discussion and hence it was necessary to point out the futility of the
small dosage of ipecac in this mixture.
The announcement that “Carminzym has proved of constantly increasing
service” is not convincing. The Council does not know of a single
clinical study of the action of Carminzym under conditions which would
have afforded satisfactory evidence of its therapeutic value.--(_From
The Journal A. M. A., Sept. 28, 1918._)
PHILLIPS’ PHOSPHO-MURIATE OF QUININE COMP.
Report of the Council on Pharmacy and Chemistry
The following report on Phillips’ Phospho-Muriate of Quinine Comp. has
been adopted by the Council and authorized for publication.
W. A. Puckner, Secretary.
Phillips’ Phospho-Muriate of Quinine Comp.[125] is sold by the Charles
H. Phillips Chemical Co., New York. According to the published formula,
each fluidram contains:
Phosphoric Acid 2 minims
Potassium Phosphate }
Magnesium Phosphate }
Calcium Phosphate } 2-1/4 grains
Ferric Phosphate }
Quinin Muriate (equal to nearly 1/2 gr. Bi-Sulph.) 1/4 grain
Strychnin 1/120 grain
Flavoring, Glycerin and Syrup, _q. s._
[125] The evolution of “Phillips’ Phospho-Muriate of Quinine Comp.”
from “Phillips’ Wheat Phosphates” may be interesting. Every one
knows that therapeutics tends to fashions, and “Phillips’ Wheat
Phosphates” appears to have had its inception as the result of the
observation that super-refined white flour contains less phosphates
than the corresponding amount of wheat. It was assumed that such
flour must be deficient in an essential constituent, and the Wheat
Phosphates preparation was apparently designed to fill the want. It was
exploited for the relief of numerous conditions that were supposed,
without satisfactory evidence, to result from this deficiency. When
iron, quinin and strychnin mixtures became the vogue a quarter of a
century ago, it was only natural to ride on the wave of popularity
and the already widely advertised “Wheat Phosphates” was further
enhanced--commercially--by the addition of the iron, quinin and
strychnin, the amount of alkaloid added being practically negligible.
Those who are not familiar with the various phases of the phosphorus,
phosphoric acid, lactophosphate, lecithin, nuclein and glycerophosphate
propaganda are referred to a report of the Council on Pharmacy and
Chemistry in The Journal A. M. A., Sept. 30, 1916, p. 1033.
Some typical claims made for the preparation are:
“With marked beneficial action upon the nervous system. To be
relied on where a deficiency of the phosphates is evident.”
“... brace those tired nerves and aid that worn stomach with
Phillips’ Phospho-Muriate of Quinine.”
“The maintenance of a satisfactory blood pressure level free from
intervals of depression may be accomplished by the use of Phillips’
Phospho-Muriate of Quinine Compound in appropriate doses.”
“The quantities of quinin and strychnin in this preparation are so
well balanced that they relieve the depression and fatigue from
mental or physical exertion, without the necessity of recourse to
alcoholic stimulation.”
“The other ingredients of Phillips’ Phospho-Muriate of
Quinine--phosphoric acid, and the phosphates of potash, magnesia,
lime, and iron--are the most rational as well as convenient
means of administering these tissue remedies, and of introducing
phosphorus--the vitalizing constituent of the nervous system--into
the organism.”
The action of such a mixture as a whole is practically that of the sum
of the actions of its constituents. The therapeutic action of strychnin
and quinin are described in every text-book of therapeutics, but it
is necessary to distinguish carefully between the various conditions
in which these alkaloids have been used without discrimination, and
those conditions in which they have been proved to be of value.
While both have been widely used in a great variety of conditions,
neither is of proved value in more than a distinctly limited range
of diseases. The manufacturers of Phillips’ Phospho-Muriate of
Quinine Comp. seem to appeal to the less discriminating who use these
alkaloids without any definite conception of exactly what they seek
to accomplish with them. Quinin, although used by the uncritical in a
host of diseases, has a definite field of usefulness in the treatment
of malaria, both prophylactic and curative, but the required dose in
the treatment of malaria is many times larger than that recommended in
the Phillips’ preparation. The claim that the “strychnin and quinin
in this preparation are so well balanced that they produce a mild,
buoyant effect, so advantageous, instead of alcoholic stimulation, to
relieve depression and fatigue from mental or physical exertion” is
nonsensical, if, indeed, it is not mendacious balderdash.
Calcium and potassium have important functions in the body, but any
deficiency that may arise is usually attributable to an inability of
the body to utilize that which is supplied, for there is seldom any
deficiency of these salts in the food, and when they are needed they
are best supplied as simple solutions of the salts in appropriate doses
without all of the other constituents of Phillips’ Phospho-Muriate of
Quinine Comp.
Phosphoric acid exerts practically the same actions as other mineral
acids, hydrochloric being usually preferred for internal administration
in certain forms of indigestion, aside from which they are seldom used
as such.
In the more recent literature for Phillips’ Phospho-Muriate of Quinine
Comp., we find the attempt to utilize the well known craze about
phosphorus, which has been through so many phases, every one of which
has had its day and has been discarded.
The phosphoric acid and phosphates present in Phillips’ Phospho-Muriate
of Quinine are of no more value in nervous diseases than is simple
sodium phosphate which does not require the addition of a host of other
ingredients for its action. As a matter of fact, the phosphates of
calcium and potassium present in a dose of Phillips’ Phospho-Muriate of
Quinine are probably devoid of appreciable effect in practically all
conditions.
To pretend that one who suffers from physical and nervous exhaustion
can be materially benefited by this mixture is sheer nonsense and is
unworthy of a moment’s consideration by a clinician who is called on to
treat such patients.
Iron is useful in anemia, as every one knows. Iron has practically no
other field of usefulness in therapeutics. When it is indicated it
should be administered in a simple form, such as the pill of ferrous
carbonate, for example, and not in a “shotgun” mixture that is quite as
likely to do harm as good.
The claim that a satisfactory level of blood pressure can be maintained
by Phillips’ Phospho-Muriate of Quinine is mentioned only to condemn
as the limit of impudent therapeutic claims. It is an insult to the
intelligence of any practitioner to pretend that any known agent or
combination of remedial agents can maintain a uniform blood pressure in
any one of innumerable conditions.
In short, Phillips’ Phospho-Muriate of Quinine Comp. is a complex and
irrational mixture exploited by means of unwarranted claims. It is
a survival of the old days of therapeutic chaos when impossible and
fantastic chemical formulas were gravely published and as solemnly
accepted without question, and also without the slightest understanding
on the part of many; when the most eminent of practitioners did not
hesitate to give glowing testimonials for lithia waters that contained
no more lithium than ordinary river water; when no therapeutic claim
was too preposterous to receive acceptance, no theory too nonsensical
to justify the use of all manner of claptrap mixtures for all manner of
conditions.--(_From The Journal A. M. A., Oct. 19, 1918._)
B. IODINE AND B. OLEUM IODINE
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on “B.
Iodine” and “B. Oleum Iodine,” together with the reply submitted by the
manufacturer and a discussion thereon by the referee in charge of the
preparations.
W. A. Puckner, Secretary.
Specimens of B. Iodine and B. Oleum Iodine (B. Iodine Chemical Company)
and an advertising pamphlet were sent to the Council by John Bohlander,
A.M., M.D., with the declaration:
“Well knowing the value of Iodin in surgical operations and
dressings, prompted me for the benefit of my fellow physicians
as well as myself, and for Humanity’s sake, to make Iodin my
master-piece in chemistry.
“After several years of diligent work in my private laboratory I
succeeded in discovering a new product of Iodin--Nitrogen, hydrate
of Iodin.”
While “B. Iodine” is said to be nitrogen hydrate of iodin and “B. Oleum
Iodine” a 5 per cent. solution thereof, the examination made by Prof.
A. H. Clark of the University of Illinois, School of Pharmacy (working
in the A. M. A. Chemical Laboratory), indicates that the first is a
simple mixture of iodin and ammonium iodid, and the second a solution
of iodin in liquid petrolatum. The Council adopted the report of the
A. M. A. Chemical Laboratory (which appears below) and declared B.
Iodine and B. Oleum Iodine inadmissible to New and Nonofficial Remedies
because:
1. The composition is incorrectly declared. B. Iodine is not a newly
discovered iodin compound, “Nitrogen Hydrate of Iodine,” but a mixture
of iodin and ammonium iodid. B. Oleum Iodine is not a 5 per cent.
solution of B. Iodine as suggested by the statement on the label and
in the advertising, but a solution of iodin in liquid petrolatum
containing about 0.85 per cent. of iodin.
2. Since B. Iodine is a mixture of Iodin and ammonium iodid, its
solution in water will have the properties of other solutions of iodin
made by the aid of iodid, such as a dilution of tincture of iodin or of
compound solution of iodin (Lugol’s solution). Hence, the therapeutic
claim that B. Iodine “being of a colloidal nature has the advantage of
being more readily absorbed and taken up by all cellular structure,
thus getting a perfect cellular medication of Iodine,” is unwarranted.
3. The names “B. Iodine” and “B. Oleum Iodine” are not descriptive of
the pharmaceutical mixtures to which they are applied.
4. B. Iodine and B. Oleum Iodine are unessential modifications of
established articles. B. Iodine has no advantage over tincture of iodin
or compound solution of iodin. (As more convenient of transportation,
the Medical Department of the U. S. Army supplies its field hospitals
with a mixture of iodin and iodid ready for solution in water, either
in tablet form or in powdered form in tubes.) Solutions of iodin in
liquid petrolatum may be readily prepared (Reports Council Pharm. and
Chem., 1917, p. 88).
[Contribution from the A. M. A. Chemical Laboratory]
B. IODINE PRODUCTS
A. H. Clark, Ph.G., B.S.
“B. Iodine” products are marketed by the B. Iodine Chemical Company,
Cincinnati, Ohio; John Bohlander, A.M., M.D., is said to be the
discoverer. They consist of “B. Iodine,” “B. Oleum Iodine,” and “B.
Aqua Iodine.” B. Iodine and B. Oleum Iodine were submitted to the
Council.
In a circular submitted by the B. Iodine Chemical Company, B. Iodine is
said to be “Nitrogen Hydrate of Iodin.” It is claimed that “coming in
contact with water, H₂O, a chemical change takes place forming Hydro
Oxid of Iodin, the Nitrogen of the Nitrogen Hydrate of Iodin escaping,
the balance taking up one of oxygen of the water. Its companion, the
H₂, escaping at the same time with the Nitrogen then combining with the
remainder of the water to form the solution of Hydrogen Oxid of Iodin;
so you can readily see that you really have a pure water of Iodin,
nothing but the H, the O and the I.”--(_From the Journal A. M. A., Feb.
1, 1919._)
B. IODINE
According to the circular, B. Iodine is soluble in alcohol, chloroform,
and ether. Also it:
“Has odor, taste, melting and boiling point, same as regular
Iodin, has a great affinity for water and will respond to all
the tests of Iodin. Appears in a Bluish Black Granulated mass or
Powder. When heated in vaporating dish will throw off large purple
volumes of Iodin leaving a slight white crystalline precipitate,
which on continuous heating will entirely disappear. With careful
manipulation you can get prismatic needle point like crystals,
looking like spores of glass, these dissolving in water will yield
pure Iodin coloring the water Iodin.
“PHARMACOLOGIC, THERAPEUTICAL AND PHYSIOLOGICAL ACTION: Same as
Iodin, being of a colloidal nature has the advantage of being more
readily absorbed and taken up by all cellular structure, thus
getting a perfect cellular medication of Iodin.”
A sample of B. Iodine, marked “Nitrogen Hydrate of Iodin” was submitted
by the manufacturers and this sample was examined.
B. Iodine was found to be a granular powder, almost black with a purple
cast. It has an odor of iodin and dissolves in water readily. It is
also quite soluble in alcohol, but not entirely soluble in chloroform
and ether. Ether quickly dissolves iodin from B. Iodine, leaving a
residue of a white granular substance. Chloroform acts the same as
ether except that the iodin is dissolved out with some difficulty. On
heating B. Iodine, vapors of iodin escape. If the heating is done on
a water bath, a residue of a white granular substance, subsequently
identified as ammonium iodid, remains. If heated in a bunsen flame, no
residue remains. These tests all indicate that iodin is held in the
form of a simple mixture.
_Ammonia_: B. Iodine when mixed with an excess of sodium hydroxid and
warmed, evolves ammonia.
_Iodine_: 0.1567 gm. B. Iodine dissolved in water required 5.88 c.c.
tenth-normal sodium thiosulphate solution indicating 48.28 per cent.
iodin. 0.3721 gm. B. Iodine required 14.18 c.c. tenth-normal sodium
thiosulphate solution indicating 48.37 per cent. iodin. The average is
48.33 per cent. iodin.
_Ammonium Iodide_: 0.3453 gm. of the residue after heating B. Iodine on
a water bath until all iodin had volatilized was dissolved in water,
acidulated with phosphoric acid, and hydrogen dioxid solution added.
The liberated iodin was extracted with chloroform and titrated with
tenth-normal sodium thiosulphate. 23.78 c.c. were required indicating
0.3447 gm., or 99.83 per cent., ammonium iodid.
A mixture of 5 gm. iodin and 5 gm. ammonium iodid has the properties of
B. Iodine mentioned above.
The conclusion is that B. Iodine is essentially a mixture of iodin and
ammonium iodid in equal parts, the two substances being finely powdered
and intimately mixed.
B. OLEUM IODINE
The following regarding B. Oleum Iodine is quoted from the circular
submitted:
“B. OLEUM IODINE: Iodine soluble in mineral oil 5 and 10% for
Nasal, Pharyngeal, Laryngeal, Bronchial, Rectal, etc., and all
meucoid affections and abnormal conditions of the mucous membrane.”
A sample of B. Oleum Iodine was submitted by the manufacturer and
examined. The label on the bottle states that it is 5 per cent. B.
Oleum Iodine in mineral oil. This sample has the characteristics of
a solution of iodin in liquid petrolatum. It is oily and has the
characteristic violet color.
_Ammonia_: B. Oleum Iodine, since it is presumed to be a solution of B.
Iodine, was examined for ammonium compounds. A small quantity was mixed
with an equal volume of strong sodium hydroxid solution and heated. No
ammonia was evolved. A few crystals of ammonium chlorid were added to
a little of B. Oleum Iodine and treated as above. Ammonia was readily
detected.
_Iodine_: 5.255 gm. B. Oleum Iodine was dissolved in chloroform and
placed in a separator. A solution of potassium iodid was added and the
iodin titrated with a tenth-normal sodium thiosulphate solution. It
required 3.5 c.c. indicating 0.85 per cent. iodin.
The conclusion is that B. Oleum Iodine is a simple solution of iodin in
liquid petrolatum to the extent of 0.85 per cent. and not 5 per cent.
as claimed. Furthermore, it is not a solution of B. Iodine since no
ammonium compound is present.
The preceding report was sent to the B. Iodine Chemical Company. The
following reply was received:
Your letter of the 21st inst., received and contents noted and
cannot quite agree with your report.
Reasons why: NH₄I, a Nitro Hydrate Iodide; NH₄I₂, a Nitro Hydrate
Iodate; and NH₄I₂I₂, Per Iodide, a molecular compound, which I
claim, they all being of a NH group, so what can be the objection
of Nitrogen Hydrate of Iodine? Of course when your chemist, with
the aid of heat, drove off all the Iodine, he naturally brought it
back to a NH₄I. There’s where he gets the A.M.. I claim a molecular
compound.
The Oil of Iodine I sent you by mistake was a 1 per cent. and not
a 5 per cent. as marked. I claim it is made from the resublimed
Iodine in mineral oil and not the B. Iodine. I claim a 5 per cent.
has heretofore never been accomplished, so I therefore can claim
something new.
Tr. Iodine contains Alcohol and Potash as a base, the alcohol a
dehydrater and Potash an escharotic, and all other soluble Iodines
like the tincture have a metallic base. Mine has not. My iodine is
compatible almost with all the salts, alkaloids, tannates, and even
the metals. You can’t say that for the tincture or the others. Now
why should mine not be superior to others?
Preparations as yet are not on the market and a few pamphlets were
printed to meet with the requirements of your rulings and approval
and shall be corrected if we only can agree on a proper name as you
may suggest.
Yours very truly,
THE B. IODINE CHEMICAL CO.
By John Bohlander, A.M, M.D.
P.S. We are sending you under separate cover another sample of the
Oil of Iodine which is a 5 per cent. solution, and allowing for
deterioration will test at least four per cent.
The referee in charge of the preparations submitted the above letter to
the Council with the following comments:
The principal statements in the letter are essentially erroneous or
misleading: Mixtures or double salts of ammonium iodid and iodin were
not discovered by Dr. Bohlander, and are nothing new. Watery solutions
of iodin by means of an iodid have long been known and used in the form
of Lugol’s solution.
There is no evidence that ammonium iodid is less irritating than
potassium iodid. On the contrary, ammonium salts are generally more
irritating than the corresponding potassium salts. B. Iodine is not
compatible with alkaloids, but behaves essentially like Lugol’s
solution. The A. M. A. Chemical Laboratory reports that the new sample
of B. Oleum Iodine contains only 1.2 per cent. of free iodin, instead
of the claimed amount. It is therefore somewhat weaker than the iodin
petrolatum prepared by the A. M. A. Chemical Laboratory (Reports
Council Pharm. and Chem., 1917, p. 88).
However good Dr. Bohlander’s intentions may be, the statements that he
makes about his products are misleading or erroneous, and the products
are ineligible for N. N. R.--(_From Reports of Council on Pharmacy and
Chemistry, 1918, p. 44._)
ANTITHYROID PREPARATIONS (ANTITHYROIDIN-MOEBIUS AND
THYREOIDECTIN) OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of antithyroid preparations (Antithyroidin-Moebius and
Thyreoidectin) has been authorized for publication.
W. A. Puckner, Secretary.
New and Nonofficial Remedies, 1918, contains a discussion
of “antithyroid” preparation and describes two of these:
Antithyroidin-Moebius (E. Merck, Darmstadt, Germany) and Thyreoidectin
(Parke, Davis & Company, Detroit, Mich.).
The referee reported that these “antithyroid preparations” evidently
have not realized the expectations of their promoters, and are viewed
with skepticism by practically all critical clinicians.
Consequently, notwithstanding the cautiously worded statements of
claims made by the manufacturers of Thyreoidectin, the Council approved
the recommendation that this preparation (Thyreoidectin) be omitted
from New and Nonofficial Remedies for conflict with Rule 6 (unwarranted
therapeutic claims) and Rule 10 (unscientific and useless articles)
(Antithyroidin-Moebius had already been omitted because it was off
the market). The Council further directed that the general article
“antithyroid preparations” be also omitted.
The Council having adopted the recommendation of the referee,
Thyreoidectin is omitted from N. N. R., while the general article
appears below, as a matter of record:
Antithyroid preparations are obtained from the blood or milk of
animals, after the removal of the thyroid glands.
The use of these preparations is based on the theory that the thyroid
gland secretes products which are toxic, but which neutralize and are
neutralized by, other toxic substances produced elsewhere in the body.
Removal of the thyroid glands would then lead to the accumulation of
these second toxic substances as evidenced by the phenomena of cachexia
strumipriva and myxedema. On the other hand, the blood or milk of
such animals is claimed to be capable of preventing the effects of
hypersecretion of thyroid substance, such as is supposed to occur
in hyperthyroidism (Basedow’s or Graves’ disease--generally called
exophthalmic goiter).
These views are largely hypothetical; attempts to give to them a
rational experimental basis have failed, but some clinical observers
report distinctly beneficial results in the milder forms of the
diseases, and in obscure nervous disorders which are supposedly
connected with thyroid hypersecretion from the administration of
the milk from thyroidectomized goats and also from the use of the
proprietary blood preparations listed below. The value of these
preparations is very doubtful. The reported improvements may only be
psychical or due to associated measures, as is often seen in this
disease. Other measures of treatment should not be neglected.
Improvement is said to occur in two or three weeks and to be indicated
by an amelioration of the nervous symptoms, tremor, palpitation,
insomnia and excitability.
The administration must be long continued. Oral and hypodermic
administration are said to be equally effective, but the former is
usually preferred. These preparations are not known to be toxic, even
when very large doses are used.--(_From Reports of Council on Pharmacy
and Chemistry, 1918, p. 50._)
CEPHAELIN AND SYRUP CEPHAELIN-LILLY OMITTED FROM N. N. R. AND
SYRUP EMETIC-LILLY NOT ACCEPTED
Report of Council on Pharmacy and Chemistry
The Council has authorized publication of the following report, which
explains the omission of cephaelin and Syrup Cephaelin-Lilly from New
and Nonofficial Remedies and the non-acceptance of Syrup Emetic-Lilly.
W. A. Puckner, Secretary.
New and Nonofficial Remedies, 1918, describes cephaelin (an alkaloid
obtained from ipecacuanha root) and lists Syrup Cephaelin-Lilly
(containing 0.088 Gm. cephaelin hydrochlorid per 100 Cc.) as a
pharmaceutical preparation of it.
The period of acceptance for Syrup Cephaelin-Lilly having expired,
Eli Lilly & Company were asked to send the current advertising and
labels so that the Council might determine if the acceptance of this
preparation might be continued. In reply the firm wrote:
“We have changed the name Syrup Cephaeline to Syrup Emetic but the
product remains the same as before. We have no circulars describing
Syrup Emetic and can only send copies of the label.”
The new name “Syrup Emetic” conflicts with the rules of the Council
in that it does not indicate the potent ingredient of this simple
pharmaceutical preparation and in that it is therapeutically
suggestive. Emetics are powerful agents, and physicians should be given
every opportunity of knowing what they prescribe for the purpose.
The name being in conflict with Rule 8, the Council voted to omit Syrup
Cephaelin-Lilly and not to accept Syrup Emetic-Lilly.
As the cephaelin syrup was the only preparation of cephaelin admitted
to New and Nonofficial Remedies, and as the alkaloid appears to have no
important therapeutic field, the Council directed that the description
of cephaelin also be omitted.--(_From Reports of Council on Pharmacy
and Chemistry, 1918, p. 52._)
COLALIN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of Colalin has been authorized for publication.
W. A. Puckner, Secretary.
Colalin is a bile salt preparation claimed to consist essentially of
hyoglycocholic and hyotaurocholic acids. It is manufactured by Rufus
Crowell and Company, Somerville, Mass., and marketed by Schieffelin and
Company, New York.
An examination of the current advertising by the referee of the Council
in charge of bile salt preparations having revealed that claims were
made for Colalin which were not in harmony with the known action of
bile preparations, Schieffelin and Company were informed that in the
opinion of the referee the Colalin circular matter required radical
revision. In this communication the referee’s objections to the claims
were set forth in detail.
No reply to this letter was received, and hence a copy of the letter
was sent to Schieffelin and Company and also to Rufus Crowell and
Company with the explanation that unless the statements in the Colalin
advertising which the referee had questioned were substantiated by
satisfactory evidence, were suitably revised, or else the advertising
matter withdrawn pending revision, the referee would be obliged
to recommend to the Council that Colalin be omitted from New and
Nonofficial Remedies.
In reply, Schieffelin and Company wrote that they were not “engaged
actively in the introduction of Colalin,” and agreed to the omission of
Colalin from N. N. R.
In view of the failure to substantiate the claims objected to or an
agreement to discontinue them, the Council directed that Colalin and
Colalin Tablets be omitted from New and Nonofficial Remedies for
conflict with Rule 6 (unwarranted therapeutic claims).
The following are the claims which the referee questioned:
“Colalin embodies the physiological function of the bile in the
intestinal canal and also possesses properties of its own which are
intimately connected with the function of the liver.”
The quotation implies that Colalin has properties essentially different
from those of bile salts, a claim which requires substantiation.
“In the liver its action seems to be that of a general stimulant of
all the hepatic functions.”
This is a claim which requires substantiation.
“By the introduction of Colalin it has therefore become possible to
actually utilize the bile for therapeutic purposes.”
This is an unwarranted claim, for bile was used therapeutically before
Colalin was introduced.
“As gall-stones are chiefly composed of cholesterin, experiments
were made to determine whether Colalin would dissolve these
concretions outside of the body. These were completely successful
and were then followed by an extensive series of clinical
investigations on persons suffering with cholelithiasis, which
demonstrated that by the administration of Colalin in many
instances gall-stones were evacuated by the natural passages and
their further formation prevented without resort to surgical
intervention.”
This is misleading in that the context shows that “without surgical
intervention” is meant to imply a connection between the experiments
showing the solvent power of Colalin and the passage of concretions.
“... Colalin not only acts as a solvent of cholesterin calculi, but
prevents their further formation by removing the causes upon which
their development depends.”
This conveys the impression that such solvent action is exerted in
the body, that is, that such concretions in the gallbladder may be
dissolved and evacuated by the use of Colalin. For this claim there is
no evidence.
“To understand the value of Colalin in intestinal disorders it is
necessary to bear in mind the important functions of the bile in
the intestinal canal, namely, its participation in the digestion of
fats, its antitoxic action, and its influence upon the peristalsis.”
“... through its antiseptic influence inhibits the production of
toxins in the intestines.”
The referee believes that there is no satisfactory evidence that bile
or bile salts can inhibit the production of toxins in that part of the
intestine--the colon--in which they are commonly produced.--(_From
Reports of Council on Pharmacy and Chemistry, 1918, p. 52._)
FORAL
Report of the Council on Pharmacy and Chemistry
The following report on Foral, a depilatory preparation, has been
authorized for publication by the Council.
W. A. Puckner, Secretary.
Foral is sold by the Foral Products Company, Pittsburgh, Pa., as an
“antiseptic depilatory” with the special claim for its use for the
removal of hair prior to surgical operation or the dressing of wounds.
In addition to claims made for its hair dissolving action, it is
asserted that, in removing the hair from an open wound, Foral acts as
“an antiseptic, which guarantees against any infection.” It is also
claimed that, though hair will return after its use, “by proper use
it will diminish the growth of hair and cause the hair to grow much
slower, and unlike the razor, the hair will not return coarser and
thicker.”
We are informed by the Foral Products Company that their preparation is
used in many hospitals and that “... one and all are well pleased and a
great satisfaction to do away with the old style razor ...”
Foral is stated to be made according to the following formula:
_To manufacture seventy-five pounds of FORAL_
Starch 35 pounds
Barium-Sulphide 20 pounds
Zinc-Oxide 10 pounds
Calcium-Carbonated-Precip. 10 pounds
Potassium-Permanganate 10 grams
Menthol-Crystallized 10 grams
Carbolic-Acid 1/2 ounce
Lilac or Citronel oil 3 ounces
The four above chemicals are going to a heating process before
mixing or sifting.
In consideration of the preceding, the Council declared Foral
inadmissible to New and Nonofficial Remedies for conflict with its
rules, thus:
1. Foral is an unessential and irrational modification of an
established article.
While its manufacturer states that Foral has been on the market for
eighteen years, the following depilatory formula appears in a book
published thirty-five years ago (A practical Treatise on Diseases of
the Skin, Louis A. Duhring, Ed. 3, 1883) and is to be found in most
books on dermatology:
Barium Sulphid 2 drams
Zinc oxid 3 drams
Starch 3 drams
Permanganates and sulphids mutually destroy each other, and therefore
the addition of the small amount of potassium permanganate cannot
serve any useful purpose. The amounts of phenol, menthol and “Lilac or
Citronel oil” are too small to exercise any effect (other than that of
a flavor) and must be considered unessential additions.
2. Foral is a pharmaceutical mixture marketed under a non-informing
name.
Whereas it is in the interest of rational medicine that physicians
should know the composition of the preparations which they use, the
name of this pharmaceutical mixture fails to indicate that it contains
the well-known and by no means always harmless barium sulphid.
3. Foral is sold under exaggerated and unwarranted claims.
In view of the small amount of phenol present and the method of using
the preparation, the claim that the use of Foral which, when operating
on open wounds, “guarantees against any infection,” is evidently
unwarranted.
There is no evidence for the claim that the use of depilatories such
as Foral retards the growth of hair or renders hair less coarse. On
the contrary, the commonly prevailing opinion is that depilation, like
shaving, makes the hair coarser.
To determine if “one and all” of those who had used Foral were still
using the preparation, four of the testimonials, appearing in an
advertising pamphlet, were investigated. The pharmacist of the
hospital from which the first of these testimonials was stated to have
emanated replied that the person whose name appeared in connection with
it had left the hospital about ten years ago and that no depilatory
preparation has been used in this hospital for some time. So far as
he knew, depilatories were not now in use in the surgical wards of
the hospital. In regard to the second testimonial, the pharmacist of
this hospital wrote that the hospital had not bought the preparation,
but that some of it had been obtained for an elderly deaconness,
who had personal use for a depilatory. The physician signing the
third testimonial replied that the preparation was effectual for the
removal of hair from the scalp, but that “... we have gotten out of
the habit of using it.” In the case of the fourth testimonial, its
asserted author wrote “... if it is applied in too large a quantity
or too concentrated, or permitted to remain on too long, it will
vesicate. It was for this reason chiefly that I discontinued its use.
It is a very bad smelling mixture and patients complain of it very
bitterly.”--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 55._)
GRANULAR EFFERVESCENT BROMIDE AND ACETANILID COMPOUND-MULFORD
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and
Nonofficial Remedies of Granular Effervescent Bromide and Acetanilid
Compound-Mulford has been authorized for publication.
W. A. Puckner, Secretary.
The Council holds that complex mixtures of remedial agents are from
every point of view inimical to therapeutic progress and therefore
to the public welfare. They are especially objectionable because it
is impossible accurately to determine the effects which follow the
simultaneous administration of a number of drugs having dissimilar
actions, and because the practice of prescribing such mixtures tends to
discourage careful consideration of the special needs of the individual
patients without which there can be no drug therapy. On the contrary,
with the use of such mixtures, therapeutic treatment becomes haphazard
and mere guesswork.
The Council, appreciating that long established customs cannot be
changed at once, has applied Rule 10, concerning the recognition of
mixtures, with the greatest leniency compatible with consistency. When
there has been a reasonable doubt concerning the value of a mixture, it
has frequently directed that Rule 10 should not apply, pending further
clinical trial of such mixture.
In no instance has subsequent experience shown that a strict
interpretation of the rule would have worked hardship or injustice.
The Council feels that there is no longer warrant for the admission of
complex mixtures to New and Nonofficial Remedies, or for the retention
of any that have been admitted, unless definite evidence of the
therapeutic value of such combinations is available. In accordance with
this decision, several mixtures now described in New and Nonofficial
Remedies will be omitted at the expiration of the three year period for
which articles are accepted.
Granular Effervescent Bromide and Acetanilid Compound-Mulford is
listed in the Appendix to New and Nonofficial Remedies. Each 100 Gm.
of the mixture contains sodium bromide, 5 Gm., and acetanilid, 1.5 Gm.
According to the label, an amount containing acetanilid, 6.5 grains,
and sodium bromide, 22 grains, is to be taken at a dose, to be repeated
in half an hour if necessary. For “children,” half this dose is
advised.
The Council has considered the available evidence for mixtures of this
sort, and has reached the conclusion that they are inimical to rational
medicine and the public, and therefore in conflict with Rule 10. It
holds that the use of mixtures of acetanilid and sodium bromide in
fixed proportion is irrational and prone to induce their indiscriminate
use by the public. Despite the perfectly frank declaration of the
composition of this mixture that is made by the Mulford Company, the
“directions” will be followed blindly and the preparation will be given
to “children” and “repeated in half an hour, if necessary” in cases in
which it would be held unwarranted to administer a dose of 3 grains of
acetanilid to a child.
The period of acceptance having expired for Granular Effervescent
Bromide and Acetanilid Compound-Mulford, the Council directed its
omission from New and Nonofficial Remedies for conflict with Rule
10.--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 58._)
HOLADIN AND BILE SALT MIXTURES
Holadin and Bile Salts-Fairchild; Capsules of Bile Salts, Succinate of
Soda and Phenolphthalein-Fairchild; Capsules of Holadin, Bile Salts and
Phenolphthalein-Fairchild; Capsules of Holadin, Succinate of Soda and
Bile Salts-Fairchild.
Report of the Council on Pharmacy and Chemistry
To explain the omission from New and Nonofficial Remedies of certain
mixtures, the Council has authorized publication of the matter which
appears below.
W. A. Puckner, Secretary.
The Council holds that complex mixtures of remedial agents are from
every point of view inimical to therapeutic progress and therefore
to the public welfare. They are especially objectionable because it
is impossible accurately to determine the effects which follow the
simultaneous administration of a number of drugs having dissimilar
actions, and because the practice of prescribing such mixtures tends
to discourage careful consideration of the special needs of individual
patients without which there can be no rational drug therapy. On the
contrary, with the use of such mixtures, therapeutic treatment becomes
haphazard and mere guesswork.
The Council, appreciating that long established customs cannot be
changed at once, has applied Rule 10 concerning the recognition of
mixtures with the greatest leniency compatible with consistency. When
there has been a reasonable doubt concerning the value of a mixture it
has frequently directed that Rule 10 should not apply, pending further
clinical trial of such mixture.
In no instance has subsequent experience shown that a strict
interpretation of the rule would have worked hardship or injustice. The
Council feels that there is no longer any warrant for the admission of
complex mixtures to New and Nonofficial Remedies or for the retention
of any that have been admitted unless definite evidence of the
therapeutic value of such combinations is available. In accordance with
this decision, several mixtures now described in New and Nonofficial
Remedies will be omitted as soon as the three year period for which
articles are accepted has expired.
The following preparations are included in New and Nonofficial
Remedies, 1918:
Holadin and Bile Salts-Fairchild.--A mixture of holadin, 5 parts, with
bile salts-Fairchild, 1 part, put up in 3 grain capsules.
Capsules of Bile Salts, Succinate of Soda and Phenolphthalein.--Each
capsule contains bile salts-Fairchild, 0.065 Gm. (1 grain); sodium
succinate exsiccated, 0.2 Gm. (3 grains), and phenolphthalein, 0.03 Gm.
(1/2 grain).
Capsules of Holadin, Bile Salts and Phenolphthalein.--Each capsule
contains holadin, 0.13 Gm. (2 grains); bile salts-Fairchild, 0.03 Gm.
(1/2 grain), and phenolphthalein, 0.065 Gm. (1 grain).
Capsules of Holadin, Succinate of Soda and Bile Salts.--Each capsule
contains holadin, 0.20 Gm. (3 grains); sodium succinate exsiccated,
0.20 Gm. (3 grains), and bile salts-Fairchild, 0.03 Gm. (1/2 grain).
Oxbile has long been credited with a cholagogue action, which, however,
has probably been greatly overestimated. When pure bile salts were
placed on the market some years ago, they and their compounds were
admitted to N. N. R.
Holadin is said to represent all the constituents of the pancreas and
to possess great potency in respect to the several enzymes, trypsin,
amylopsin, lipase, and the milk-curdling ferment.
It is not clear when such a substance is indicated therapeutically.
While it may be useful when there is a deficiency of pancreatin and
gastric secretion, it should be used alone.
It is also quite possible that bile salts may have a distinct, though
limited, field of usefulness when there is a deficiency of biliary
secretion; but the bile salts are best administered alone, or in
combination with such laxatives as may be deemed necessary by the
physician while keeping in mind the fact that different patients
show the widest difference in their reaction to laxatives, making
combinations of these agents in fixed proportion irrational.
Phenolphthalein was popularized by nostrum makers; and while it has
some therapeutic value, this has been greatly overestimated, and it
should be used only in amounts deemed necessary for each patient,
preferably alone.
Succinate of sodium was introduced as a saline cathartic, with the
claim that it exerts an antiseptic action on the biliary passages and
gallbladder. There is no satisfactory evidence to substantiate this
claim.
The Council maintains a liberal attitude toward new preparations, but
it feels that it is impossible to determine the value of the several
constituents of such complex mixtures when used as such; it holds
that these mixtures are superfluous and that the several substances
of which they are composed should be used singly or at most with
greater attention to the individual requirements of the patient than is
possible when these fixed mixtures are prescribed.
Despite the fact that these mixtures have been in use for more than
nine years, there is no satisfactory evidence that they possess any
advantage over the simple laxatives or the preparations of bile or
pancreatic extract. They are therefore held to be in conflict with Rule
10, and the Council has directed that they be not included in N. N. R.
after Dec. 31, 1918.
Having adopted the preceding report, the Council, in accordance with
its regular procedure, submitted this to Fairchild Bros. and Foster for
comment.
The following reply was received:
We are entirely at variance with you in the arbitrary conclusion
expressed concerning the inimical influence of mixtures on
therapeutic progress, the practice of medicine and the public
welfare.
If the combinations of Holadin and Bile Salts, etc., in capsules,
were ever properly within the scope of New and Nonofficial
Remedies, they should be retained. If, however, complex mixtures
are to be held as, a priori, unworthy of consideration, the
rejection of all would naturally be a logical proceeding.
We believe that the particular combination of Holadin and
Bile Salts etc., have been clearly in the line of therapeutic
progress--a natural evolution, improvement and development.
For many years combinations of pancreatic extract and ox gall had
naturally suggested themselves.
When we realized the fact that the bile salts were quite clearly
the active principles of the bile, and that they must necessarily
exist in greatly varying percentages in the official inspissated
or ox gall, and also because these ox gall products of pharmacy
were of extremely varying density, even from that of treacle
to resin--and of other objectionable character, we undertook to
prepare bile salts.
These combinations are now further justified in view of
physiological considerations, the simultaneous secretion of the
pancreas and bile, and the state of our knowledge of the function
of bile salts, and as co-ferments, promoting and supplementing the
pancreas enzymes.
The question suggested as to whether the cholagogic action of ox
gall (and bile salts) has been overestimated seems to us no clear
purport. The bile salts are obviously employed as the means of
administering and thus realizing whatever properties this secretion
may have in medicine, of which the cholagogic action is by no means
the only consideration.
As for phenolphthalein, which is credited with purely laxative
properties, we are at a loss to see any bearing in the remark that
phenolphthalein was popularized by nostrum makers. We cannot see
that the physician’s or chemist’s estimate of phenolphthalein, its
properties and uses, can be in the least degree influenced one
way or the other by the statement that “phenolphthalein has been
popularized by nostrum makers.”
The phenolphthalein and succinate of soda combinations were
originally both prescribed, and we have simply placed them at the
service of the physician without other exploitation of them than
that designed to call attention to their use in the conditions
indicated.
These combinations are offered in a form which may be administered
by the mouth with the best promise of introducing the substance
more directly in the intestinal tract during the digestion period
or at such interval after or prior to, the digestion period, as
would best, in the judgment of the physician, meet the indications.
These particular combinations are especially desirable in these
“fixed forms” since they are stable and reliable resources at the
command of the physicians, the enzymes retaining their stability
and potency without material deterioration for many years, and they
naturally possess the advantages which are obviously due to the
character of the particular pancreas and bile products used in the
combinations.
Furthermore, the hygroscopic and soluble organic substances in
admixture cannot extemporaneously be so prepared in sealed capsules
as to be readily available under the practical requirements of
prescribing and dispensing. And we do not believe that those
who practice medicine will be in accord with your view that the
pancreas substance should necessarily be administered alone, or the
bile substance alone.
It now appears that these combinations are to be dropped from New
and Nonofficial Remedies in consequence of the view, so stated,
that in clinical experience “for more than nine years there is no
satisfactory evidence that they possess any advantage over the
simple laxatives or preparations of bile or pancreatic extract.”
In reply to this we would simply make the following comment:
During these “nine years” these combinations have inevitably been
put to an informing clinical trial, because of the fact that they
have been employed with success in disorders of the pancreas and
bile functions and often in chronic and serious cases where the
clinical conditions were obvious and unmistakable.
The reports of these cases come to us from physicians widely
separated and each of his own independent initiative. It would
seem gratuitous, to say the least, to state that the observers are
“disinterested,” since it is quite clear that there is no other
interest than that of the practitioner and his patient.
It is not a case of a new drug or combinations of new remedies,
but simply resources which, upon well grounded reasons, both from
a theoretical and material standpoint, justify clinical trial, and
with results which would seem from any ordinary human standpoint to
be satisfactory clinical evidence.
As to the interpretation of competent clinical evidence by the
Council, we would, in view of the circumstances and without
comment, ask to embody in this text this rule:
“Clinical Evidence.”--“To be acceptable, the clinical evidence
must offer objective data with such citation of authority as
will enable the Council to confirm the facts and establish the
scientific value of the conclusions drawn. Clinical data are
worthless when the author is not cited. The facts on which
claims with regard to the value of a remedy are based must have
been rendered accessible for investigation and confirmation by
disinterested observers, either through publication or through
the records of a hospital or other institution.”
To discredit these combinations would seem to us not only
unjustified, but sterile of any real advancement in medicine, or of
anything in the way of helpfulness to the patient in the class of
cases in which these products have been resorted to with benefit;
this on no other ground really than the opinion “that they have no
advantage over the simple preparations themselves.”
Naturally we shall continue to prepare these products and shall
continue to take such action as we deem best to bring them to the
attention of the physician, for the conduct of our business must
remain in the hands of those who are personally responsible for it.
And it is now forty years since we took up this line of work and
with the declared intention of devoting ourselves to the applied
science of the digestive ferments and “to their development and
practical application in every useful purpose in medicine.”
We have been consistently in sympathy with the fundamental purpose
of the Council, which must first rest upon fact as to the character
of the products offered as medicinal agents. The weight of
evidence justifies the position that these particular products
rationally should be, and as a matter of fact are, of important
special service in the utilization of these organic secretions in
medicine.
As explained in the preceding report, the Council holds that complex
mixtures of remedial agents are from every point of view inimical
to therapeutic progress and therefore to the public welfare. They
are especially objectionable because it is impossible to determine
accurately the effects which follow the simultaneous administration
of a number of drugs having dissimilar actions, and because such a
practice tends strongly to discourage careful consideration of the
special needs of individual patients without which there can be no
therapeutic progress. On the contrary, with their use, therapeutic
treatment becomes haphazard and mere guesswork.
The dismissal of the holadin and bile salts mixtures does not involve
the question of the usefulness of holadin or of bile salts alone; on
the contrary, the possible usefulness of these preparations is admitted
in the report. It is the combination of holadin, bile salts, sodium
succinate and phenolphthalein to which objection is made.
The statement of Fairchild Bros. and Foster that “these combinations
are now further justified in view of physiological considerations”
is somewhat misleading. It is true that bile and the pancreatic
secretion cooperate in intestinal digestion, but there is no evidence
that in every case in which there is a deficiency of one of these
secretions there is also a deficiency of the other, and it is an axiom
of scientific therapeutics that no drug or remedial agent should be
administered except to fill a definite want. Otherwise the practice of
therapeutics becomes mere empiricism.
The properties of phenolphthalein are not in the least influenced by
the manner of its introduction, as Messrs. Fairchild Bros. and Foster
emphasize; but the important fact in this connection is that the
popular conception of their actions is greatly influenced by the mode
of introduction, and phenolphthalein has been widely advertised in a
variety of conditions, so that the popular notion concerning it is not
that of scientific therapeutics.
In short, the entire argument of Messrs. Fairchild Bros. and Foster
concerning the exploitation of these preparations may be summed up by
saying that they have been used by clinicians who believe that good
results have followed their use, and that the firm will therefore
continue to supply the demand. The tendency of some to use anything
brought to their notice, and the readiness of manufacturers to market
anything that physicians will use, presents the greatest obstacle
to therapeutic progress. There was never a nostrum so irrational or
worthless that honest but undiscriminating clinicians could not be
found who reported wonderful results from its use.
According to Fairchild Bros. and Foster, these holadin and bile salts
mixtures have been in use for some nine years. Yet the Council is not
aware of any investigation of their merits that meets the requirements
of scientific research.
The Council is not acquainted with a single clinical investigation of
their action under conditions which afford satisfactory evidence of
their therapeutic value.
It is obviously wholly insufficient for a clinician to report that the
use of a mixture was followed by good results. The fallacy of such
arguments was demonstrated long ago. He must make a comparison of the
results obtained with the remedial agent with those obtained in as
nearly similar conditions as possible except for the use of the agent.
We are not aware that any such study of the mixtures in question has
been made. It is in the last degree irrational to hold that because
bile salts are the active constituents of bile, therefore such complex
mixtures as these are necessary.--(_From Reports of Council on Pharmacy
and Chemistry, 1918, p. 59_)
LIQUOR SANTAIVA, S. & D., OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of Liquor Santaiva, S. & D., has been authorized for
publication.
W. A. Puckner, Secretary.
So far the Council has applied Rule 10 concerning the recognition of
mixtures with the greatest leniency compatible with consistency. When
there has been a reasonable doubt concerning the value of a mixture, it
has frequently directed that Rule 10 should not apply, pending further
clinical trial of such mixture.
In no instance has subsequent experience shown that a strict
interpretation of the rule would have worked hardship or injustice. The
Council feels that there is no longer any warrant for the admission of
complex mixtures to New and Nonofficial Remedies or for the retention
of any that have been admitted, unless definite evidence of the
therapeutic value of such combinations is available.
The Council being engaged in the annual revision of New and Nonofficial
Remedies, the referee in charge of santal preparations reported that
the three year period of acceptance had expired for Liquor Santaiva
(Sharp & Dohme).
The referee held that Liquor Santaiva, S. & D., declared to be a
solution of santal oil and copaiba with aromatic oils, in a mixture
of alcohol and water, is plainly in conflict with the current
interpretation of Rule 10, because there was no sound evidence
to indicate that any useful end is gained by the simultaneous
administration of santal oil and copaiba in any proportion, and that
so, of course, there is no evidence of the special advantage in the
fixed proportions represented by the mixture. He pointed out that the
formula is essentially a survival of the discredited shotgun gonorrhea
mixtures and therefore recommended that its acceptance be not continued.
The Council agreed to the recommendation of the referee and directed
that Liquor Santaiva, S. & D., be omitted from New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 66_)
MALTZYME, MALTZYME WITH CASCARA SAGRADA, MALTZYME WITH COD LIVER OIL,
MALTZYME FERRATED AND MALTZYME WITH YERBA SANTA
OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of the Maltzyme preparations has been authorized for
publication.
W. A. Puckner, Secretary.
In 1916, the Council voted to omit Maltzyme with Hypophosphites, and
Maltzyme with Phosphate of Iron, Quinine and Strychnine. At that
time the labels used on the Maltzyme preparations still in New and
Nonofficial Remedies contained a list of Maltzyme combinations which
included those which had been dismissed. As the Council does not permit
an accepted article to be used as a means of advertising an article
not accepted, it voted to continue the following preparations for
a period of three years on condition that reference to the deleted
articles be omitted from the labels when those then in stock had been
used up: Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod
Liver Oil, Maltzyme Ferrated and Maltzyme with Yerba Santa. While the
Maltzyme Company made no definite agreement to revise its advertising
propaganda in accordance with the Council’s requirements, the Maltzyme
preparations were retained in the belief that in due time the required
revision of the labels would be made.
The Council being engaged in preparing the 1919 edition of New and
Nonofficial Remedies, the referee in charge of malt extracts reported
that the Maltzyme Company had not revised its labels in accordance with
the stipulation of the Council. The referee further reported he had
become convinced that the claim that Maltzyme is “rich in malt enzymes”
is unwarranted and that the term “Maltzyme” (malt plus enzyme) is
misleading; this because of the recognized instability of malt extracts
(Jour. A. M. A., March 30, 1912, p. 954) and because the Maltzyme
Company makes no definite statement with regard to the diastase (malt
enzyme) content of its preparations.[126] For this reason it had
been the referee’s intention to propose the deletion of all Maltzyme
preparations when their period of acceptance expired in 1919. As,
however, the present Maltzyme preparations are in contravention with
the Council’s requirements, he recommended that the acceptance of these
preparations be canceled now.
[126] Manufacturers are warned by the Department of Agriculture,
through the Bureau of Chemistry, that combinations claiming to contain
digestive enzymes must be active when sold. If preparations tend to
deteriorate in a short time, each lot should be dated and not sold
after the period when they become inactive. While every manufacturer
must be considered innocent until proved guilty, and ignorant until
proved knowing, it is a matter of knowledge that manufacturers have
marketed their various digestive mixtures with full appreciation of
their worthlessness.--(Jour. A. M. A., Dec. 19, 1914, p. 2234.)
The Council agreed to the recommendation of the referee and directed
that Maltzyme, Maltzyme with Cascara Sagrada, Maltzyme with Cod Liver
Oil, Maltzyme Ferrated, and Maltzyme with Yerba Santa be omitted from
N. N. R.--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 67_)
METHAFORM OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of Methaform has been authorized for publication.
W. A. Puckner, Secretary.
Methaform is the proprietary name applied by F. Stearns & Co. to
chlorbutanol.
Being engaged in the annual revision of New and Nonofficial Remedies,
and the term of acceptance for Methaform having expired, a trade
package was purchased to determine if the product was marketed in
compliance with the rules of the Council. It was then found that a
circular was wrapped with the trade package which advertised Methaform
Inhalant, a preparation not accepted for New and Nonofficial Remedies.
For obvious reasons, the Council does not countenance the use of an
accepted article as a means of advertising an article not accepted.
Accordingly F. Stearns & Co. was advised that the Council would
be obliged to withdraw the acceptance of Methaform unless the
objectionable circular was omitted from the Methaform packages.
Stearns & Co. did not give the requested assurance, and therefore the
Council directed that Methaform be omitted from New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 68_)
PINEAL GLAND, RED BONE-MARROW AND THYMUS GLAND AND THEIR PREPARATIONS
OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of pineal gland, red bone-marrow and thymus gland and their
preparations has been authorized for publication.
W. A. Puckner, Secretary.
Pineal gland, red bone-marrow and thymus gland were admitted to New
and Nonofficial Remedies when these products gave promise of having
therapeutic value.
The term of acceptance for the preparations of pineal gland, red
bone-marrow and thymus gland having expired, the referee in charge of
animal organ preparations recommended in his report for the annual
revision of N. N. R. that these products and the general articles
describing them be omitted from New and Nonofficial Remedies. He held
that the experimental and clinical experience with them leads to the
conclusion that they are without value.
In accordance with the recommendation of the referee, the Council voted
that the following preparations be omitted from New and Nonofficial
Remedies: Desiccated Pineal Gland-Armour; Pineal Gland Tablets-Armour;
Extract of Red Bone-Marrow-Armour; Desiccated Thymus-Armour; Thymus
Tablets-Armour.
As a matter of record, the descriptive articles for pineal gland, red
bone-marrow and thymus gland, which appeared in New and Nonofficial
Remedies, 1918, are given below.
Pineal Gland
The functions of this gland have not yet been established but there
is some pathological and some experimental evidence that there is
a relation between the gland and some processes of development and
growth; the nature of this relation is unknown. Adiposis is a frequent
sign of disturbed pineal function, but observers are not agreed whether
to interpret this as indicating hypofunction or hyperfunction, or
possibly a concurrent disturbance of the pituitary. In some instances
intravenous injections of pineal extract have seemed to cause a
distinct fall in blood pressure. It has been inferred from observations
in cases of pineal tumors in the young that the gland in young
individuals furnishes a secretion which inhibits growth, particularly
the development of the reproductive glands, but the results of
experimental administration of pineal substance orally have led other
observers to infer that the pineal secretion favors physical and
possibly mental and sexual development. It has been suggested that, as
all evidence points to the fact that the function of the pineal gland
is one of early life, extract of adult pineal glands might be expected
to be inert. Experiment has also indicated greater activity in glands
obtained from young animals than in those obtained from older ones. The
Council has decided to admit preparations of pineal gland to New and
Nonofficial Remedies simply for experimental purposes.
Red Bone-Marrow
Red bone-marrow consists largely (more than 90 per cent.) of fat. In
new-born animals a third or more of this fat consists of lecithin.
The marrow of the bones of new-born animals contains iron (up to 1
per cent. or more) in various forms of organic combination. Both
lecithin and iron decrease rapidly in the first weeks after birth.
The commercial preparations contain very variable amounts of these
constituents.
_Actions and Uses._--Red bone-marrow is supposed to stimulate the
formation of red blood corpuscles; whatever action it may have in this
direction is probably due largely to the iron and lecithin which it
contains.
It is said to be useful in simple and pernicious anemias.
Thymus Gland
Little is known as to the functions of the thymus, but it is believed
to have an important relation to growth. There also seems to be some
relation between the thymus and thyroid, for the former is frequently
abnormal in diseases involving the latter (hyperthyroidism).
The use of thymus is purely empirical. It has been employed in the
treatment of hyperthyroidism, rickets, tuberculosis, hemophilia, and
infantile marasmus and atrophy; its use in the latter conditions
is said to be the most promising. It is claimed on very doubtful
grounds to exert a somewhat favorable effect in certain cases of
cancer.--(_From Reports of Council on Pharmacy and Chemistry, 1918,
p. 69_)
PIPERAZINE AND LYCETOL OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The following report explaining the omission from New and Nonofficial
Remedies of Piperazine and Lycetol has been authorized for publication.
W. A. Puckner, Secretary.
Piperazine (diethylenediamene) and Lycetol (a methyl derivative of
diethylenediamene) were accepted for New and Nonofficial Remedies in
1906. Both Piperazine and Lycetol were asserted to be efficient uric
acid solvents and efficacious remedies in the treatment of gout and
rheumatism. These products have been retained until now because there
was no investigation which definitely showed their uselessness as uric
acid solvents, though their use is generally admitted to have been
disappointing.
From an exhaustive and critical study of the available evidence,
Hanzlik (Jour. Lab. & Clin. Med., February, 1917) concluded that
scientific evidence, though limited, and clinical opinion indicate that
Piperazine is valueless in gout and that there is sufficient scientific
evidence to indicate the worthlessness of Lycetol.
The referee in charge of Piperazine and Lycetol recommended that these
products be omitted from New and Nonofficial Remedies for the reason
that they have been sufficiently tried to justify the conclusion that
they are not of value. The period of acceptance having expired, the
Council directed that Piperazine and Piperazine Tablets (The Bayer
Company, Inc.) and Lycetol (The Bayer Company, Inc.) be omitted from
New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy
and Chemistry, 1918, p. 70._)
STANOLIND LIQUID PARAFFIN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
As explained in the report which follows, “Stanolind Liquid Paraffin”
was omitted from New and Nonofficial Remedies at the request of the
proprietors. Announcement of this omission was made in the preface to
New and Nonofficial Remedies, 1918, but publication of the Council’s
report was postponed pending actual conflict with the rules. The
Council now authorizes publication of the report because a circular
indirectly advertising the product to the public was found enclosed
with the trade package of Stanolind Liquid Paraffin.
W. A. Puckner, Secretary.
Stanolind Liquid Paraffin was admitted to New and Nonofficial Remedies
in 1916, when its method of marketing conformed to the rules of the
Council. This brand of liquid petrolatum, by action of the Council,
has been omitted from New and Nonofficial Remedies on request of the
Standard Oil Company of Indiana, its manufacturer, who wrote to the
Secretary of the Council stating that:
“In order that our facilities for the manufacture of this oil shall
be constantly engaged, it will be necessary for us to find sales
on a larger scale than in the past. To do this under our present
advertising and marketing arrangement we feel will be impossible.”
This letter, in addition, suggested “that physicians are not
prescribing Stanolind Liquid Paraffin in any considerable proportion
of their orders” and “that the situation which now confronts us would
not be materially helped if Stanolind was specified in all such
prescriptions.” Further, the Council is asked to consider whether
it “might be willing to declare this preparation as not a Council
product,” on the alleged grounds that “liquid paraffin is not medicinal
in its action and passes through the digestive tract in practically
unaltered condition.”
The Council holds that Stanolind Liquid Paraffin is a drug, and that,
therefore, its direct advertising to the public is in contravention
of the Council’s rules. Constipation should be treated by dietary
and hygienic means. Evacuants are only temporary measures. Liquid
petrolatum is medicinal; it greatly modifies the intestinal flora; it
acts as a lubricant and emollient; it modifies the absorptive powers
of the intestinal mucous membrane; it is capable of influencing the
digestion of fats. In short, liquid petrolatum, being a drug, its
indiscriminate and excessive use should not be encouraged.--(_From
Reports of Council on Pharmacy and Chemistry, 1918, p. 72_)
WESTERFIELD’S DIGITALIS TABLETS
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following report and authorized its
publication.
W. A. Puckner, Secretary.
Westerfield’s Digitalis Tablets (The Westerfield Pharmacal Co., Dayton,
Ohio) are claimed to represent a fat free tincture of digitalis and to
be “enteric coated.” It is claimed that because of this coating these
tablets pass the stomach unchanged and dissolve in the intestine, and
that this obviates any possibility of gastric disturbance.
The circular which sets forth the asserted advantages of the tablets
states that digitalis contains a fat which is an irritant to the
gastric membrane. It also contains the following:
“We feel no hesitation in saying that if this remedy is given a
fair trial where it is properly indicated, the result obtained will
be a gratifying surprise.
“It is a common expression from physicians who have tried this
remedy to say, ‘Surely I have never used Digitalis before.’”
If these quotations mean anything, they imply that these tablets
present a distinct advance in digitalis therapy. There is no warrant
for such a claim. The statement with reference to the occurrence of an
oil in digitalis is partly false and partly misleading. Tincture of
digitalis, which the tablets are claimed to represent, is fat free;
the fixed oil that is present in the drug is not soluble in 70 per
cent. alcohol, the menstruum used for the preparation of the official
tincture of digitalis. Furthermore, a fairly large amount of this oil
(such as is present in 100 therapeutic doses of the drug) is incapable
of causing gastric disturbance. Gastric disturbance is a side action
that is inseparable from slight overdosage with all true digitalis
bodies and is not in any way due to local gastric action. The claim
that such action is prevented by the use of enteric pills or tablets is
obviously false and misleading.
The alleged “common expression from physicians who have tried this
remedy” does not constitute acceptable evidence of the value of the
preparation.
The Council declared Westerfield’s Digitalis Tablets inadmissible to
New and Nonofficial Remedies because unwarranted therapeutic claims are
made for this product.
When the preceding report was submitted to the Westerfield Pharmacal
Co., a reply was received indicating that the firm did not know
that progressive manufacturers had discontinued the claim that “fat
free” digitalis preparations were devoid of gastric effects. It also
submitted a revised circular, which, however, reiterated the claim that
the tablet presented a distinct advance in digitalis therapy in that it
was “fat free,” and coated to prevent disintegration in the stomach.
Since tincture of digitalis and extract of digitalis are practically
devoid of fatty material, and since it is now well known that the
fat does not cause gastric disturbance and that therapeutic doses
of digitalis do not exert a local irritant action on the stomach,
the manufacturer’s product and the claims made for it merely tend to
perpetuate old errors.
The Council declared Westerfield’s Digitalis Tablets inadmissible
to New and Nonofficial Remedies on the ground that this presents an
unessential modification of pills of an official substance. It directed
publication of its report with this explanation.--(_From Reports of
Council on Pharmacy and Chemistry, 1918, p. 75_)
XEROFORM-HEYDEN AND BISMUTH TRIBROMPHENATE-MERCK
OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on
Bismuth Tribromphenate-Merck and Xeroform-Heyden. These two products
were found not to comply with the standards for bismuth tribromphenate
adopted for New and Nonofficial Remedies, and hence could not be
retained. As the manufacturers of both products announce that efforts
toward the production of a satisfactory product are continued, the
omission of the two brands is without prejudice to their reacceptance
when a satisfactory product becomes available.
W. A. Puckner, Secretary.
The referee in charge of bismuth preparations submitted the following
report of the A. M. A. Chemical Laboratory which shows that
Xeroform-Heyden and Bismuth Tribromphenate-Merck do not comply with the
adopted standards for bismuth tribromphenate.
Some time ago a request was received from the Medical Section
of the National Council of Defense for a report on a brand of
bismuth tribromphenate. In accordance with this request the firm’s
product was examined, and at the same time and for comparison, an
examination was also made of a specimen of bismuth tribromphenate
received from Merck and Company, October, 1915, and of another
specimen of bismuth tribromphenate “Xeroform-Heyden” obtained from
the Chicago branch of the Heyden Chemical Works in April, 1918.
The examination brought out that the bismuth tribromphenate
submitted to the national Council of Defense contained a large
amount of uncombined tribromphenol, while the specimen of
Xeroform-Heyden contained an excessive quantity of bismuth.
When the latter finding was submitted to the Heyden Chemical Works,
the firm stated: “The product had to be made in this country after
importations from Europe became impossible and the first lots were
not fully up to the standard ...” The firm stated that it could now
furnish a product which it considered fully equal to that which
was previously imported, and offered to submit “samples of the new
material.”
Having been requested to do so, a specimen of Xeroform-Heyden was
received from the Heyden Chemical Works, New York. This and a
second specimen, purchased from a Chicago wholesale drug house,
were examined. Whereas the standards for bismuth tribromphenate
which had been formulated by the Laboratory and accepted by the
Heyden Chemical Works required that the product should contain
from 40 to 49 per cent. of bismuth and contain not more than 3.3
per cent. of uncombined tribromphenol, the specimen purchased in
Chicago contained 67.7 per cent. of bismuth, while the specimen
received direct from the Heyden Chemical Works contained 24 per
cent. of uncombined tribromphenol. When this result was reported to
the Heyden Chemical Works, the firm replied:
“It seems that we are not yet in a position to supply a product
that answers a uniform standard and that we have to continue our
efforts in this direction.
“We will take this matter up with you again as soon as we have
been successful ...”
At the time when the preceding examination was being made,
bismuth tribromphenate-Merck could not be obtained from the
Chicago wholesale houses. A request sent to Merck and Company
for a specimen of the market supply brought the information that
the product was temporarily unavailable. Though unable to supply
the product, the firm gave valuable advice for a revision of the
somewhat loosely drawn tests for bismuth tribromphenate in New and
Nonofficial Remedies, 1918.
Recently (November, 1918) Merck and Company sent a specimen of its
product labeled “Bismuth Tribromphenate-Merck” “Merck and Company,
New York, Distributors and Guarantors,” and wrote “... You will
notice this sample conforms in nearly all details to the tests we
submitted with our letter of June 4th. We have been able to produce
better goods, but just at present unsatisfactory starting material
confronts us. The sample conforms to N. N. R., 1918, but will not
meet the test for uncombined tribromphenol submitted by you in your
letter of September 4th ...”
Examination of the specimen demonstrated that it was soluble to a
considerable extent in alcohol (the N. N. R., 1918, description
provides that it should be only slightly soluble in alcohol)
and according to the standards adopted for New and Nonofficial
Remedies, 1919, contains 18 per cent. uncombined tribromphenol
(more than five times the permitted amount).
In view of the Laboratory’s report, the referee recommended that the
acceptance of Xeroform-Heyden and Bismuth Tribromphenate-Merck be
withdrawn, without prejudice to their reinstatement when satisfactory
products are again offered for sale. The Council adopted the
recommendation of the referee, and accordingly Xeroform-Heyden and
Bismuth Tribromphenate-Merck are omitted from New and Nonofficial
Remedies, 1919.
When the Laboratory’s findings with regard to Xeroform-Heyden and the
action of the Council deleting the article from New and Nonofficial
Remedies was reported to the Heyden Chemical Works, the firm expressed
regret that efforts to produce a product equal to that formerly
obtained from Germany had so far not been successful and announced
that it had decided to withdraw Xeroform-Heyden from the market for the
present.
When Merck and Company was advised in regard to the report of the
Laboratory and the Council’s action, this firm questioned the
feasibility of producing a product meeting the Council’s standards and
suggested that the test for free tribromphenol be revised to permit as
much as 15 per cent. of this constituent. When Merck and Company was
reminded that its product, submitted in 1915, essentially complied with
the adopted standards and that the estimate of the therapeutic value
of bismuth tribromphenate is based on a product essentially free from
alcohol-soluble material, the firm replied:
“As stated in our letter of the 12th inst. we do not wish to market
the chemical unless it meets all legitimate requirements of the
physicians that use it. If, therefore, your standard proves to be
good and it is commercially possible to make supplies conforming to
it, we shall do so. We shall discontinue the article unless it is
of suitable quality.”
--(_From Reports of Council on Pharmacy and Chemistry, 1918, p. 76._)
CREAM OF MUSTARD REFUSED RECOGNITION
Report of the Council on Pharmacy and Chemistry
Cream of Mustard, The Cream of Mustard Co., South Norwalk, Conn., is
said to be made by mixing 2 drachms of oil of mustard and 2 drachms
of oil of turpentine with one pound of white petrolatum. According to
the label it is “for Tonsillitis, Rheumatism, Sore Muscles, Croup,
Pleurisy, Frosted Feet, Sore Throat, Neuralgia, Sprains, Bronchitis,
Headache, Chilblains, Stiff Neck, Congestion, Bruises, Asthma, Lumbago,
Pains and Aches, Colds in Chest.”
The Council refused recognition to Cream of Mustard:
Because it is a simple pharmaceutical mixture of well-known ingredients
and has no advantage over established rubefacients which every
physician knows how to prescribe and every pharmacist to compound.
Incidentally, the name “Cream of Mustard” is misleading and not
descriptive of the composition of this pharmaceutical of oils of
mustard and turpentine.--(_From Reports of Council on Pharmacy and
Chemistry, 1918, p. 79_)
“PLURIGLANDULAR” MIXTURES
Caps. Adreno-Spermin Comp., Caps. Antero-Pituitary Comp.,
Caps. Placento-Mammary Comp., Caps. Thyro-Ovarian Comp.,
Caps. Hepato-Splenic Comp., Caps. Pancreas Comp., and
Caps. Thyroid Comp., Not Admitted to N. N. R.
Report of the Council on Pharmacy and Chemistry
After considering the evidence for the several “pluriglandular”
mixtures described below, the Council declared them inadmissible to
New and Nonofficial Remedies. The Council’s action was communicated
to the manufacturer, Henry R. Harrower, in accordance with the usual
procedure. After giving due consideration to the manufacturer’s reply
the Council authorized publication of the report which appears below.
W. A. Puckner, Secretary.
With the offer “to supply you with as much literature as may be
necessary and as little of the actual remedies as may be desired” if
“the prospects for the inclusion of these formulas in N. N. R. are
good,” Henry R. Harrower sent the Council a booklet descriptive of his
preparations and labels for the following mixtures:
_Caps. Adreno-Spermin Comp._, each said to contain “Adrenal Gland
(total) gr. 1/4, Thyroid Gland (U. S. P.) gr. 1/12, Spermin
Extr. (from Gonads), Brain and Spinal Cord aa gr. 1, Calc.
Glycerophosphate q. s. ad gr. 5.”
_Caps. Antero-Pituitary Comp._, each said to contain “Anterior
Pituitary Body gr. 2, Thymus Gland gr. 1, Thyroid Gland (U. S. P.)
gr. 1/12, Calcium-phosphorus Comp. q. s. ad gr. 5.”
_Caps. Placento-Mammary Co._, each said to contain “Desiccated
Placenta gr. 2, Mammary Substance gr. 1-1/2, Pituitary Body (total)
gr. 1/3, Calcium-phosphorus Comp. q. s. ad. gr. 5.”
_Caps. Thyro-Ovarian Comp._, each said to contain “Desic. Corpora
Lutea Ovarian Substance gr. 2-1/2, Thyroid Gland (U. S. P.) gr.
1/12, Pituitary Gland (total) gr. 1/8, Calcium-phosphorus Comp. q.
s. ad gr. 5.”
_Caps. Hepato-Splenic Comp._, each said to contain “Liver
Parenchyma, Spleen Substance aa gr. 2, Powd. Bile Salts gr. 1/2,
Adreno-Spermin Co. (No. 1) gr. 1.”
_Caps. Pancreas Comp._, each said to contain “Adrenal Gland,
Pituitary Gland (total) aa gr. 1/2, Ovarian Substance gr. 1,
Pancreas Substance q. s. ad gr. 5.”
_Caps. Thyroid Comp._, each said to contain “Desic. Thyroid Gland
(U. S. P.) gr. 1/8, Calcium-phosphorus Comp. q. s. ad gr. 5.”
The Council declared these preparations inadmissible to New and
Nonofficial Remedies, for reasons which follow:
1. Each of the mixtures contains one ingredient or more, which is
neither recognized in the U. S. Pharmacopeia nor admitted to New and
Nonofficial Remedies, namely: “Spermin Extract,” “Brain,” “Spinal
Cord,” “Desiccated Placenta,” “Liver Parenchyma,” “Spleen Substance,”
“Pancreas Substance” and “Calcium Phosphorus Comp. (Each 100 gm.
represents Magnes. Phos. 1; Calc. glycerophos. 4; Potas. bicarb. 15;
Sod. bicarb. 22 and Sod. chlor. q. s.).” For obvious reasons the
Council does not accept a mixture containing an indefinite ingredient
and hence it would be necessary as a preliminary for the consideration
of any one of the mixtures that their unofficial ingredients be
made eligible for New and Nonofficial Remedies by the submission of
evidence that such ingredient is of uniform composition and that it is
therapeutically valuable when given by mouth. There is no evidence that
many of these organs have any value whatever when administered by the
mouth or in any other way.
2. In the light of our knowledge the administration of gland mixtures
in the host of conditions enumerated in the advertising circular is
irrational and on a par with the use of the shotgun mixtures once in
vogue.
Be it a pharmaceutical mixture, a “mixed” vaccine, or a
“pluriglandular” product, the combination of two medicinal ingredients
in a mixture must be considered contrary to rational therapy unless
a good reason exists for such combination. Such mixtures are held in
conflict with Rule 10 unless the manufacturer presents acceptable
evidence for the value of his combination. A physician may prescribe
any mixture which he considers indicated in a given case, but the
marketing of mixtures of drugs in fixed proportions is in most
instances irrational and a detriment to sound therapy.--(_From The
Journal A. M. A., Jan. 18, 1919_)
CERELENE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
declaring Cerelene inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Cerelene, a paraffin preparation for the treatment of burns, was
submitted to the Council by the Holliday Laboratories, with the
statement that it was composed of 84 per cent. paraffin, 15 per cent.
myricyl palmitate, and 1 per cent. purified elemi gum to which is added
oil of eucalyptus 2 per cent. and betanaphthol 0.25 per cent. It was
explained:
“Myricyl Palmitate is a purified form of Beeswax, free from all
impurities, acids, etc., which is solely manufactured by this
Company....”
It was also stated that on “special order” Cerelene has been made
containing oil of eucalyptus and resorcin, oil of eucalyptus and picric
acid, and picric acid alone. The following report on the preparation
was presented to the Council by the referee to whom Cerelene had been
assigned:
Cerelene is another compound wax for the treatment of burns.
According to the work of Sollmann (J. A. M. A., 68:1799, 1917) it
is highly improbable that compound mixtures have any advantage over
simple paraffin of low melting point. Cerelene must therefore be
considered as an unessential modification of paraffin, and as in
conflict with Rule 10; unless definite evidence of superiority is
submitted. Cerelene mixtures containing medicinal ingredients also
appear unscientific since the evidence that the ingredients do not
leave the wax has not been successfully contradicted. Finally, the
claims made for Cerelene are rather extreme, and would need some
revision before they could be accepted.
The A. M. A. Chemical Laboratory reports:
The physical properties of Cerelene are as follows:
Melting point 50.0 C. by U. S. P. method.
Ductility limit 30.5 C.
Plasticity limit 26.4 C.
Not strong at 38 C.
Adheres moderately well; detaches with “pulling.” On heating,
readily loses eucalyptol, and a small amount of resinous substance
forms in the bottom of the beaker. If Cerelene is heated to 145 C.
and cooled, the resulting product no longer has the properties of
the original Cerelene.
It is recommended that the preceding report be sent to the Holliday
Laboratories, and that unless its superiority over simple paraffins is
demonstrated and the unwarranted claims abandoned, Cerelene be declared
inadmissible to New and Nonofficial Remedies for conflict with Rules 6
and 10.
This report was submitted to the Holliday Laboratories with the
information that it had been adopted, Oct. 3, 1917. It was also
explained that before Cerelene could be accepted, the unofficial
and unstandardized constituent “myricyl palmitate” would have to be
considered and accepted for New and Nonofficial Remedies since, for
obvious reasons, the Council does not accept a preparation which
contains an unofficial and unstandardized substance not in N. N. R.
The Holliday Laboratories acknowledged receipt of the Council’s report
and asked that the matter be held in abeyance until the requested
evidence had been obtained. Later the Council was advised that the
advertising circulars for Cerelene had been withdrawn with the
exception of one giving directions for its use. Five months later, the
firm stated that experiments were being made “to determine the actual
strength of Cerelene in comparison with other paraffin waxes....”
Nothing further has been heard from the Holliday Laboratories and no
reply has been received to an inquiry made Oct. 12, 1918. The Council
therefore authorizes publication of its report declaring Cerelene
inadmissible to New and Nonofficial Remedies.--(_From the Journal
A. M. A., Feb. 15, 1919_).
COLLOSOL COCAINE NOT ADMITTED TO N. N. R
Report of the Council on Pharmacy and Chemistry
The report which appears below was adopted by the Council and sent to
the Anglo-French Drug Co., Ltd., New York, for comment in December,
1918. No explanation has been received from the manufacturer. For
the information of the profession the Council has now authorized
publication of the report.
W. A. Puckner, Secretary.
“Collosol Cocaine” was submitted to the Council in October, 1918, by
the Anglo-French Drug Co., Ltd., New York, under the claim that it was
an “absolute colloid” and that it contained “1 per cent. cocain.” The
label on the submitted specimen declares:
“Collosol Cocaine 1-100”
“... the Cocaine exists as the pure alkaloid in the Colloidal
state--the condition in which it is isomorphic with the protein
of the body fluids. The effect is more prolonged than that of
a molecular Cocaine Solution and being _non-toxic_ absorption
presents no practical danger.”
The product was assigned to the Committee on Pharmacology for
consideration. The following report was submitted and its adoption by
the Council recommended by the committee:
“Collosol Cocaine” is said to be a colloidal form of cocain and
is alleged to possess a remarkably low toxicity. The subjoined
report of the A. M. A. Chemical Laboratory, however, shows that the
preparation does not have the composition claimed for it and it is,
in effect, misbranded. In fact, the English manufacturers concede
that it is not an “absolute colloid” and that the declaration with
regard to the percentage of cocain is incorrect.
It is recommended that, without considering other conflicts with
the rules of the Council at this time, “Collosol Cocaine” be
declared inadmissible to New and Nonofficial Remedies for conflict
with Rule 1 which requires that the composition of an article
must be correctly declared. The report of the A. M. A. Chemical
Laboratory is appended.
REPORT OF THE A. M. A. CHEMICAL LABORATORY
Simpson, Hewlett and Eyre (_Lancet_, April 28, 1917, p. 660) reported
“Collosol Cocaine” to be much less toxic than cocain. These writers,
however, did not verify the statements as to the composition and in
the light of subsequent chemical examination it is not to be wondered
at that “Collosol Cocaine 1.0 per cent.” was much less toxic than a
solution containing 1.0 per cent. of cocain hydrochlorid.
Barger, Dale and Durham report from the Department of Biochemistry
and Pharmacology, Medical Research Committee (_Lancet_, Dec. 1, 1917,
p. 825), that they examined “Collosol Cocaine” and found it to contain
but 0.25 per cent. of cocain. They also found that the cocain was not
present in a colloidal form. Discussing the low toxicity claimed by the
manufacturers, these investigators state:
“In the samples which we examined the toxicity was, indeed, much
lower than that of an ordinary 1 per cent. solution of a cocain
salt; but the local anesthetic action was low to a corresponding
degree, and both actions corresponded satisfactorily with the
proportion of cocain chemically recoverable from the solution.”
Stroud, of the Crookes Laboratory (which manufactures the preparation),
who apparently had been informed of this work in advance of
publication, admits the correctness of it, and states (_British Medical
Journal_, Nov. 24, 1918, p. 710) that “whilst the colloidal protective
apparently absorbs a portion of the cocain, the remainder is found not
to exhibit the attributes of a colloid,...”
The specimen of “Collosol Cocaine” submitted to the Council and labeled
“Collosol Cocaine 1-100” was found to contain at most 0.4 per cent.
cocain. The examination was made in accordance with the method used by
Barger, Dale and Durham and calculated as cocain. This method, however,
probably would not distinguish between cocain and basic decomposition
products, but would include all as cocain in the amount found. The
specimen of “Collosol Cocaine” examined was neutral or slightly acid, a
fact which tends to confirm the conclusion of the British investigators
that “Collosol Cocaine” contains cocain in noncolloidal form and
precludes an increased physiologic effect due to alkalinity.
The Council adopted both the report submitted by the committee and that
of the A. M. A. Laboratory and declared “Collosol Cocaine” inadmissible
to New and Nonofficial Remedies.--(_From The Journal A. M. A., April
12, 1919._)
CUPRASE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on
Cuprase, sold by the Anglo-French Drug Co., Ltd. The Council’s
criticisms of the advertising claims were sent to the firm, December,
1918. The firm made no reply and essentially the same claims are
contained in recent advertisements.
W. A. Puckner, Secretary.
“Cuprase” is now being advertised and sold in the United States by the
Anglo-French Drug Co., Ltd., the firm which also markets it in England.
It is said to be “prepared in the Laboratories of F. Ducatte, 8 Place
de la Medeleine, Paris.” According to an advertising circular entitled
“The Medical Treatment of Cancer” “Cuprase” is “chemical colloidal
copper”; in another place it is “a colloidal copper hydroxid,” which is
said to be obtained chemically by the reduction of salts of copper in
the presence of albumosic acid.
A box (price $8.50 less 10 per cent. discount) of “Cuprase-Doctor Gaube
du Gers” was purchased recently from the Anglo-French Drug Co., Ltd.
It contained eight ampules each containing approximately $1 $2$3 of a
brownish fluorescent liquid. No information of composition was given
on the box, except the line: “Chaque ampoule contient: $1 $2$3 .00121
de Cuivre pur” (Each ampule contains O.00121 gr. of pure copper). The
A. M. A. Chemical Laboratory reports that the preparation does contain
a small amount of copper, with some protein material and about 1 per
cent. sodium chlorid.
The therapeutic claims in the advertising circular are those
commonly made for cancer “cures” and are about equally convincing.
The publication of such statements and quotations as the following,
which appear in a pamphlet “The Medical Treatment in Cancer,” cannot
be too strongly condemned in a medicament that at best has only an
experimental status:
“A special preparation, Cuprase, has been introduced into
therapeutics which has been remarkably successful. In the history
of the therapeutics of cancer, nothing has been found which can
compare with the effects produced by means of Cuprase. Clinical
facts carry greater weight than theoretical deductions. It
follows, from the clinical observations which I have collected,
that in the large majority of cases Cuprase effects the diminution
or disappearance of the pains, an improvement in the general
condition, a diminution or arrest of the neoplasms, and finally
in certain cases, a cure has been effected. It should be remarked
that all or nearly all the observations refer to inoperable cases
in which the prognosis was unfavorable at an early date. It is
needless to emphasize the practical importance of a preparation
capable of yielding such results, even relative, in the worst
stages of a disease which has always been regarded as absolutely
resisting the action of all internal remedies.”
“To sum up, Cuprase has given positive results in about 94 per
cent. of the cases in which it has been employed for a sufficiently
long period, and some brilliant results in about 20 per cent. of
these cases. Therefore, it may be affirmed, that among the internal
remedies for cancer, Cuprase is the one which has produced the most
successful results, and can, under certain circumstances, compete
with surgical methods, even, so far as the rapidity of their
results are concerned.”
“It is indicated:
(a) apart from all operation, and as a specific and curative
remedy;
(b) before an operation, in order to give tone to the patient,
mobilise the tumor, destroy its toxins;
(c) after the operation, as a tonic and anti-toxic, and in order
to avoid frequent relapses which are always possible.”
Essentially the same statements are made in the more recent
advertisements (f. i. Urological and Cutaneous Review, Feb., 1919).
Opposed to these loose statements are the results of Richard Weil
(The Journal A. M. A., 1913, Sept. 27, p. 1034; ibid, 1915, April 17,
p. 1283). Weil avoided pitfalls of subjective impressions and used
as the essential criterion of efficiency “the demonstrable reduction
in size of a tumor, of a kind not to be attributed to the natural
processes of evolution of that tumor or of its associated lesions” (l.
c. 1915, p. 1289).
The available evidence for Cuprase is far from meeting this criterion.
That published by the manufacturers and agents presents only vague
generalities, and no definite data. The evidence gathered by Weil
himself permits an estimate of the value of Cuprase and it is entirely
unfavorable. He states (l.c. 1915, p. 1288):
“Colloidal copper has been used in recent time for the same purpose
by Gaube du Gers and by others. I have recently examined the effects
of colloidal copper on malignant tumors in man, and have been unable
to find that it has any therapeutic value. Furthermore, a study of
the distribution of the copper in tumors obtained at operation or by
necropsy from individuals so treated failed to show that the copper had
been deposited therein.”
In view of the extravagant and cruelly misleading therapeutic claims,
and the indefinite statements of composition, the Council voted
Cuprase ineligible to N. N. R., and authorized the publication of this
report.--(_From The Journal A. M. A., April 12, 1919._)
COLLOSOL PREPARATIONS
Report of the Council on Pharmacy and Chemistry
The Council has adopted and authorized publication of the report which
appears below declaring “Collosol Argentum,” “Collosol Arsenicum,”
“Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol
Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin”
and “Collosol Sulphur” inadmissible to New and Nonofficial Remedies,
because their composition is uncertain (conflict with Rule 1). In the
few cases in which the therapeutic claims for these preparations were
examined, the claims were found to be so improbable or exaggerated
(conflict with Rules 6 and 10) as to have necessitated the rejection of
these products.
W. A. Puckner, Secretary
The Anglo-French Drug Co., Ltd., London and New York, in November,
1918, requested the Council to consider the products “Collosol
Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,”
“Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol
Manganese,” “Collosol Quinin” and “Collosol Sulphur.” The term
“Collosol” appears to be a group designation for what are claimed to
be permanent colloidal solutions, marketed by the Anglo-French Drug
Co., Ltd. Were this claim correct, “Collosols” should contain their
active constituents in the form of microscopic or ultramicroscopic
suspensions, protected against spontaneous precipitation by the
presence of proteins or some similar “stabilizers.”
According to the original patent specifications for Collosols, the
metals are precipitated or treated with “peptone,” which acts as the
suspending or stabilizing agent. The method of using the peptone makes
it doubtful, in the first place, whether the major part of the metals
is present in colloidal form, or merely in the form of peptonates,
i. e., as ordinary salts. Moreover, the later patents indicate that the
products have been unsatisfactory; “experience having shown that some
metal colloids under certain conditions not yet fully understood have
the tendency to break down after a certain period” (U. S. patent No.
1,116,247). Phenol, it is claimed has a tendency to counteract this
decomposition, and the patent covers the use of phenol for this purpose.
It is difficult to see how phenol could possibly have such action. In
fact, it obviously does not, for a number of the samples of Collosols
submitted to the Council had separated. For instance, “Collosol
Hydrargyrum” was not a colloidal solution at all, but a suspension
of a coarse powder. The ampules of “Collosol Ferrum” contained a
considerable quantity of flocculent precipitate. If either of these
preparations were injected intravenously as directed, death might
result, making the physician morally if not legally liable.
The recklessness of the claims is further illustrated by the advice
that these indefinite mixtures of poisonous metals can be injected in
unlimited quantities. Thus, Henry Crookes stated (_Chemical News_,
May 7, 1914, p. 218) that Collosols “contain so small a proportion of
metal, viz., 1 in 2000, that even a poisonous body like arsenic can be
used with impunity.” He stated that they may be applied as a lotion,
intramuscular or intravenous injection, and that “one pint or more can
be injected intravenously.”
In the case of “Collosol Cocain,” as was brought out in the Council’s
report published in The Journal, April 12, 1919, the manufacturers have
admitted that the product is not what they have claimed--and still
claim--for it. The report of the A. M. A. Chemical Laboratory showed
that “Collosol Cocain,” instead of containing 1 per cent. cocain as
claimed, contained, in fact, at most not more than 0.4 per cent. cocain.
The report of the A. M. A. Chemical Laboratory on the Collosol products
was sent by the Council to the New York office of the Anglo-French Drug
Co., Ltd., in duplicate in order to facilitate reference to the London
office. This was some months ago. The information which the Council
requested has not yet been received, nor has the Anglo-French Drug Co.,
Ltd., indicated its intention of supplying such information. On the
other hand, claims to which specific objection have been made, continue
to appear in current advertising. Accordingly, the Council authorizes
publication of this report, and declares the Collosol preparations
previously named ineligible to New and Nonofficial Remedies.
Additional Notes on Collosol Evidence
In addition to the preceding the following notes of the referee on the
evidence so far submitted were sent to the Anglo-French Drug Company,
Ltd., for consideration:
_Collosol Iodine_: The leaflet which describes Collosol Iodine contains
claims that are improbable, not in accord with accepted facts nor
substantiated by evidence; for instance:
“This preparation contains Iodine in its most active form ...”
“The disadvantages of ‘iodism’ and nausea frequently associated
with iodides never occur with Collosol Iodine.”
“In the case of Colloidal Iodine the whole of the Iodine is
absorbed and enters into molecular combination with protein to form
an iodo-amino acid and ... exerts a reducing action on the lipoids
producing a different condition of the blood--hence the use of
Iodine as an ‘alterative’.”
“Intravenously the action of Collosol Iodine is more rapid ... in
cases of pyemia ... thus showing its absolute non-toxicity.”
“‘Per se’ Colloidal Iodine is only slightly parasitotropic and
bacteriotropic but micro-organisms are very greatly influenced
by its action, and not only is the effect of a subsequently
administered remedy greatly increased but also the insoluble
colloidal protein of serum itself is reduced to smaller particles,
thus increasing its surface and adsorptive capacity and consequent
germicidal power. In some cases the serum, thus aided, is enabled
to throw off a milk microbial invasion. The above action can be
readily demonstrated ‘in vitro’ by means of the ultramicroscope.”
“In Cancer, the intravenous injection of Collosol Iodine relieves
pain, even where large dosage of morphine is ineffective.”
“In Rheumatism the ionic method of treatment with Collosol Iodine
is strongly advised.”
“In Recovery from Alcoholism the internal administration of
Collosol Iodine restores the normal condition of cell activity,
ensuring rapid recovery.”
_Collosol Hydrargyrum_: This is said to be a preparation of colloidal
mercury and would therefore be similar to Electromercurol (New and
Nonofficial Remedies, 1919, p. 167). Colloidal mercury preparations
have been used to some extent; they appear to have no decided
advantage over other, noncolloidal, mercury compounds. They differ
sufficiently from them, however, to justify acceptance for New and
Nonofficial Remedies, providing that reasonable claims are made for
them. The leaflet advertising Collosol Hydrargyrum contains statements
that cannot be accepted and require thorough revision to make them
acceptable. The following are instances:
“Although--especially locally--the action of mercurials is markedly
antiseptic, when taken internally or injected, it has been stated
by some of the best known authorities, that their action is rather
to increase the natural resisting power of the body to disease,
probably because of stimulation of the oxidases.”
With the soluble mercurials “considerable upset of the normal cell
conditions of the tissues ensues whilst these soluble salts are
being converted to a condition in which the body can make use of
them.”
“The colloidal state ... is stated by some authorities in the case
of mercury to be invariably precedent to absorption.... With the
usual forms of mercury the danger of too great a dose per cell is
considerable, but in the case of colloidal mercury, the diffusion
is extremely rapid and chemical affinity low. Hence the danger
to the individual leucocyte is minimized and the maximum effect
obtained.”
“... absence of pain is usual in the administration of colloidal
preparations and is due to their isomorphism with the colloidal
lipoid and protein of the tissues and body fluids.”
“According to McDonagh,... mercury acts as an oxidizing agent and
that the process of oxidation is more effective in the early stages
of syphilis in producing the death of the causal organism....”
_Collosol Manganese_: The circular submitted to the referee is
a reprint of a paper by Sir Malcolm Morris on “The Treatment of
Furunculosis and Other Deep-Seated Coccogenic Infections by Collosol
Manganese.” It reports four cases of furunculosis, each of which
cleared up after the intramuscular injection of a few doses of Collosol
Manganese. The author seems to attribute the cure to the manganese
but the evidence is not convincing. Even the author admits that, in
the treatment of furunculosis in general “when at last the dismal
procession ends, this often appears to be less the result of treatment
than because the disease has run its natural course.” Unless much
better evidence is in existence, the preparation must be considered
to conflict with Rule 6, which requires therapeutic claims to be
substantiated.
_Collosol Argentum_: The evidence submitted as to actions consists of
a single reprint by Roe, which is not convincing, and this fantastic
statement by Boys:
“A young girl, aged 18, came to my house with acute inflammation of
one eye with an ulcer on the cornea. Two drops of Collosol Argentum
were dropped in the eye at 7 p. m., and a pad placed over the eye.
When she came next morning the eye was quite well; the ulcer had
disappeared, and there was no inflammation.”
There is no evidence that this preparation acts as catalyzer and
assists the natural resisting bodies of the tissues; or that these are
“oxygen carriers.” Unless the claims are supported by better evidence,
they, in the opinion of the referee, could not be accepted.
There have been submitted to the Council samples of the following
metallic Collosols:
COLLOSOL ARGENTUM COLLOSOL FERRUM
COLLOSOL ARSENICUM COLLOSOL HYDRARGYRUM
COLLOSOL CUPRUM COLLOSOL MANGANESE
Also Collosols of Iodine and Sulphur, and finally Collosols of Cocain
and Quinin. Of all the above, except sulphur, only three small ampules
have been submitted. This does not admit of any chemical examination
but a statement of the physical appearance may be of interest.
_Collosol Arsenicum_, 0.2 per cent.: Very turbid with large quantities
of a lemon yellow flocculent precipitate. On shaking does not become
homogeneous and rapidly separates again.
_Collosol Argentum_, 1-2000: The liquid has a slight opalescence. There
is considerable deposit of a heavy black precipitate. Does not become
homogeneous on shaking and the black substance quickly separates again.
_Collosol Cuprum_, 0.5 _per cent._: Dark red somewhat opalescent
liquid. No precipitate. May be colloidal.
_Collosol Ferrum_, 1-2000: Liquid clear. Large quantities of dark brown
flocculent precipitate. The precipitate is not distributed evenly when
the mixture is shaken and settles out quickly on standing.
_Collosol Hydrargyrum, 5 per cent._: Milky liquid. Large quantities of
white deposit mixed with considerable black. The deposit mixes fairly
well but the greater part settles out after standing an hour or two.
_Collosol Manganese_, 2.5-1000: Clear reddish-brown liquid without
deposit of any kind. Is not opalescent or fluorescent.
_Collosol Iodin_, 1-500: Very pale straw colored liquid without
deposit. Has a slight opalescence.
_Collosol Sulphur_, 1-100: Liquid is opalescent. There is some deposit
of yellow particles. A four ounce bottle was also submitted. The liquid
in this bottle is milky with considerable deposit of yellow crystals
like ordinary crystalline sulphur.
_Collosol Cocain_, 1-100: Transparent, colorless liquid with no
deposit. Chemical examination showed 0.4 per cent. of what may have
been cocain. This residue gave alkaloidal tests.
_Collosol Quinin_, 1-100: Slightly opalescent, colorless liquid, with
no deposit. Gives alkaloidal reactions.--(_From The Journal A. M. A.,
June 7, 1919._)
PULVOIDS CALCYLATES COMPOUND
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report, not
so much because the preparation with which it deals is of any great
importance, but as a protest against the large number of similar
irrational complex mixtures which are still offered to physicians.
W. A. Puckner, Secretary.
Pulvoids Calcylates Compound (The Drug Products Co., Inc.) are tablets
each of which is claimed to contain:
“Calcium and Strontium Disalicylate, 5 grs.; Resin Guaiac, 1/2 gr.;
Digitalis, 1/4 gr.; Cochium [colchicum?] Seed, 1/4 gr.; Squill,
1/4 gr.; Cascarin, 1/16 gr. with aromatics.”
“Pulvoids Calcylates Compound (Sugar coated orange color)”
is advertised (_Medical Times_, January, 1919) as being
“Analgesic-Antipyretic and Diuretic,” and is included in the
preparations designated by the advertiser as “Approved Remedies for
LaGrippe and ‘Flu.’” The claim that “Their tolerance is remarkable”
refers not to the physicians who tolerate such products, but to the
alleged fact that Pulvoids Calcylates are tolerated remarkably well.
The advertisement continues:
“May be given persistently and continuously without gastric
disturbances.”
“They are uniformly efficient. More certain in effect than the
ordinary Salicylates.”
It would be difficult to find an advertisement of equal length
containing a greater number of misleading or directly false statements
than are found in this one. The Journal (April 22, 1916, p. 1307) has
called attention to the lack of justification for this absurd mixture
of drugs and has discussed the preparation with especial reference to
its use in acute rheumatism, in which the salicylates occupy a special
field. The advertisement just quoted mentions La Grippe and “Flu” (or
Influenza) as special fields of usefulness for this preparation. This,
apparently, is merely an attempt to spread the sail for any breeze.
Salicylates have a field of usefulness in influenza in that they
often afford relief from pain. There is no reason to suppose that a
mixture containing calcium and strontium salicylates--the “Calcium and
Strontium Disalicylate” of Pulvoids Calcylates is probably a mixture
of calcium and strontium salicylate[127]--has any greater salicylic
effect than an equal amount of sodium salicylate. On the other hand, it
is worse than useless to give colchicum, squill and digitalis for the
relief of such pains.
[127] See report, The Journal, Sept. 9, 1916, p. 827.
Should cardiac dilatation develop, and digitalis medication be
required it would be impossible to adjust the dose of such a mixture
with special reference to the digitalis action, which alone would be
indicated for that condition. No educated physician at present would
think of giving resin of guaiac merely because his patient required
digitalis, nor would he administer “cascarin,” whatever that may be, in
fixed doses, every time he gave a dose of salicylate.
It is impossible to recognize the several effects induced by this
therapeutic omneity, and the medical profession should consider it an
insult to be offered mixtures such as Pulvoids Calcylates Compound.
Pulvoids Calcylates Compound is, per se, of no great importance; it is
one of a type. It has been selected as one of the utterly irrational
and therefore potentially dangerous mixtures, that may be found by
the score or the hundred in the catalogues of practically every
pharmaceutical manufacturing firm in the United States.--(_From The
Journal A. M. A., June 14, 1919._)
PROTEOGENS OF THE WM. S. MERRELL COMPANY
Report of the Council on Pharmacy and Chemistry
The Council has adopted and authorized publication of the statement
which appears below, declaring Proteogen No. 1 (Plantex) for Cancer,
Proteogen No. 2 for Rheumatism, Proteogen No. 3 for Tuberculosis,
Proteogen No. 4 for Hay Fever and Bronchial Asthma, Proteogen No. 5
for Dermatoses, Proteogen No. 6 for Chlorosis, Proteogen No. 7 for
Secondary Anemia, Proteogen No. 8 for Pernicious Anemia, Proteogen
No. 9 for Goitre, Proteogen No. 10 for Syphilis, Proteogen No. 11
for Gonorrhea, and Proteogen No. 12 for Influenza and Pneumonia
inadmissible to New and Nonofficial Remedies because their
composition is secret; because the therapeutic claims made for them
are unwarranted; and because the secrecy and complexity of their
composition makes the use of these preparations irrational.
The Council took up the consideration of the Merrell Proteogens because
of inquiries received, and on January 27 invited the Merrell Company
to aid in the proposed investigation by submitting information in
regard to the composition of the preparations, submitting the current
advertising, and presenting evidence for the claims that were made
for the preparations. While the Merrell Company agreed to submit the
requested information, this had not been received at the time the
report of the referee to whom the products had been assigned (Referee
1), was adopted. This report was sent to the company on April 4. In
reply the Merrell Company protested against the conclusions of the
report and submitted considerable material in an attempt to support
the claims made for the products. This material was examined by the
first referee and then transmitted to a second referee (Referee 2) for
consideration. The second referee concluded that the matter submitted
offered no evidence that would justify the Council in modifying the
report first adopted, and hence recommended that its publication be
authorized.
In accordance with this recommendation (report of Referee 2) the
Council authorized the publication of the reports of both the first and
second referees.
W. A. Puckner, Secretary.
Report of First Referee on Proteogens
“Proteogens,” according to the William S. Merrell Co., are “Polyvalent
Proteins of Non-Toxic Plant Origin.” The subject of Proteogens can
best be approached by recalling the history of “Autolysin,” an
alleged remedy for cancer, originated by A. S. Horowitz, Ph.D. This
was exploited some years ago, and was finally shown to be worthless.
Proteogens are said to be prepared “under the personal supervision of
the originator, Dr. A. S. Horowitz.” The composition of the different
Proteogens is essentially secret. The assertion was made at one time,
but is not found in the present advertising matter, that Plantex--now
called “Proteogen No. 1”--is similar to Autolysin. Now the Proteogens
are said to be “prepared by a special process employing various
combinations of plants.” Further:
The biologic principles present are chlorophyll, chromoplast,
lipoids and vitamines; these are ferments or enzymes. The vegetable
acids, metalloids and metals present in all plants in colloid form
act biochemically. Among the metalloids are hydrogen, carbon,
manganese, oxygen, sulphur, phosphorus and chlorine; the heavy
metals are iron, potassium, sodium, magnesium and copper. These
biochemic principles are always present in plants as colloids.”
It is claimed by the Merrell Company that:
“Proteogens stimulate the cytogenic mechanism to higher activity;
therefore, indirectly cleave the invading microorganism and
eliminate their special toxins. Proteogens swing the disturbed
metabolism back to normal and, by natural processes, build up
effective defenses against recurrent bacterial attacks.”
Proteogen No. 1 was first introduced as “Plantex,” and at that time the
Merrell Company referred to a preparation that was the result of “a
series of studies” carried out by a “noted biologist” with a view of
“evolving a Cancer remedy” that was “to be autolytic in character,” and
announced:
“The House of Merrell always interested in the progress of plant
therapy, began pharmacological experimentations to reproduce this
same substance. The qualitative and quantitative analysis of the
substance as used in New York having been published simplified
matters. A somewhat similar remedy has now been prepared. It
consists of the following substances--Menyanthes trifoliata
[Buckbean], Melilotus officinalis [Yellow sweet clover], Mentha
crispa [Curled mint], Brassica alba [White mustard], Anemone
hepatica [Liver leaf], Viola tricolor [Pansy], Anthemis [Roman
chamomile], Fructus colocynthidis [Colocynth], Lignum quassiæ
[Quassia], Urtica dioica [Nettle], Radix rhei [Rhubarb root], Hedge
hyssop. These substances are in approximately equal proportions
with the exception of the mustard which forms 20 per cent. of the
mixture, and the colocynth fruit which is 5 per cent.”
With respect also to the other Proteogens listed above, study of
medical literature revealed no evidence establishing their therapeutic
value; in fact, no evidence was found other than that appearing in
the advertising matter of the manufacturer. The range of diseases in
which Proteogens are recommended is so wide as to make obvious the
lack of scientific judgment which characterizes their exploitation. A
circular letter, received January, 1919, reminded the physician that
about a year ago his attention had been directed to Proteogen No. 1
for cancer, that later developments enabled the firm to recommend for
his consideration “a series of Proteogens (Nos. 2 to 9),” and that now
“In response to an insistent demand, Dr. A. S. Horowitz has prepared
two new Proteogens--No. 10 for Syphilis and No. 11 for Gonorrhea.”
A postscript to this circular letter announced another preparation,
“Proteogen No. 12 for Influenza and Pneumonia,” a “development out of
the present influenza epidemic,” and admitted that “It has not had
the clinical experimentation that precedes our introduction of a new
product.”
The introduction of No. 12 was effected by means of a special bulletin
which consists exclusively of clinical reports from seven physicians,
all from Chicago save one, and all purporting to show most favorable
results from No. 12. They describe cases which any physician with
experience with influenza can duplicate without any special treatment.
It is difficult to give serious consideration to a set of alleged
remedies when the only evidence is that furnished by the proponents of
the alleged remedies. This is particularly true when the alleged remedy
does not make a sufficient appeal to one’s sense of the rational in
therapeutics to lead one to feel justified in asking a trial at the
hands of careful clinical observers. Considering the grave nature of
the diseases for which Proteogens are recommended, particularly cancer,
tuberculosis, and pernicious anemia, the want of a rational basis
for the method of treatment and the general tenor of the advertising
matter, it appears safe to conclude that these agents do not represent
any definite advance in therapeutics.
As the use of preparations, secret in composition, and of no
established value, is contrary to rational therapy, it is recommended
that the Proteogen preparations be declared in conflict with Rules 1, 6
and 10.
Report of Second Referee Reviewing Manufacturers’ Reply
The report declaring the Proteogens of the William S. Merrell Company
inadmissible to New and Nonofficial Remedies was adopted by the
Council, but before publication it was sent to the Merrell Company
for such comments as it might desire to make. In due time the reply
of the firm was received. It consisted of two volumes bound in limp
morocco, each stamped in gold: “Report Proteogen Therapy Requested by
the American Medical Association, 1919; The Wm. S. Merrell Company.”
The first volume contained 79 pages of typewritten material; the second
volume contained 76 pages of typewritten material and a number of
advertising booklets put out by the Wm. S. Merrell Company, exploiting
the Proteogens.
Among the typewritten material was a 14-page report on “Proteogen
Therapy” by its originator, A. S. Horowitz. Following this there
are several pages devoted to what is termed “a short qualitative
description of the ingredients of major importance in Proteogens.”
Then follows a page describing the advertising of Proteogens, and
the remainder of the two books is devoted to testimonials, lauding
the benefit of Proteogens in diseases such as cancer, tuberculosis,
rheumatism, asthma, influenza, enlarged prostate, rheumatic
endocarditis, syphilis, eczema, psoriasis, diabetes, secondary anemia,
gonococcic infections, etc. Finally, there are attached samples of
advertising pamphlets.
The dissertation by A. S. Horowitz contains little actual information
concerning these substances, but is concerned principally with
discussion of foreign proteins, “antiferments,” “non-specific
proteins,” “anti-virolins” and speculations on their hypothetical
actions and interactions on each other and on the organs of the body
and on bacteria. The report contains many questionable statements.
One finds in this report but few definite statements of facts which
are known to be accurate or which could be accepted without question.
The qualitative description of the proteins and their components is
as vague as the previous discussion. The differentiation between the
various Proteogens is extremely indefinite; that for Tuberculosis,
No. 3 is described as “polyvalent, non-specific protein which rapidly
attacks the acid-fast, encapsulated tubercle bacilli”; Proteogen No.
10 for syphilis is said to be a combination of “non-specific plant
proteins and different chemicals which has the power to paralyze and
destroy living spirochete.” It is stated that Proteogens are scientific
preparations based on standard ingredients and that the standardization
is more accurate than in serums, vaccines or toxins, etc. The report
gives no proof of such statements.
The testimonials that are submitted are typical of “reports” that
manufacturers are able to obtain from some physicians, to prove the
efficacy of almost any preparation in any disease. Each consists,
practically, of the opinion of the individual who has employed the
Proteogens or the opinion of the patient who has been treated. Few data
are given in these reports from which an impartial conclusion might be
drawn. A few of the testimonials presented by the William S. Merrell
Company follow. The valuelessness of such material as scientific
evidence is obvious:
RHEUMATISM:--_Proteogen No. 2._--The Doctor has one case being
treated with No. 2. She has improved so rapidly she cannot express
her pleasure, and will continue for some time on the treatments.
She is a patient who was confined during the time she suffered from
a rheumatic illness, and it seemed to affect her mental condition.
This condition is clearing up also, very much to the pleasure of
both patient and doctor.--November 27, 1918.
INFLUENZA:--_Proteogen No. 12._--First day, temperature 102,
gave 1 c.c. Proteogen No. 12; second day, temperature 100,
gave 1 c.c. Proteogen No. 12; third day, temperature 98.8,
gave 1 c.c. Proteogen No. 12, and then discharged the case as
recovered.--October 31, 1918.
ASTHMA:--_Proteogen No. 4._--Splendid results obtained from a
sample of Proteogen No. 4. Three ampoules affected [effected?]
complete recovery.--October 9, 1918.
CANCER:--_Proteogen No. 1._--Mrs. B. pronounced recovered from
Cancer by Dr. O. W. A., of Catlin, after having injections of
Proteogen No. 1 for some time.--October 4, 1918.
ECZEMA:--_Proteogen No. 5._--Tried No. 5 on a patient with
eczema, and with happy results. Have not done anything for him
for about five months--and he is now at his business. Proteogen
No. 5 also RELIEVED HIM OF CONSTIPATION AND WHAT HE CLAIMED A
TRAUMATIC STRICTURE OF THE LOWER PORTION OF SIGMOID FLEXURE.
He is sure pleased and recommending them to his friends.
(Proteogens).--February 17, 1919.
SYPHILIS:--_Proteogen No. 10._--I am getting such excellent results
with the No. 10 Proteogen for Syphilis that I am badly in need of
more, as I am treating so many cases. Please send me four dozen
C. O. D.--October 9, 1918.
ENLARGED PROSTATE:--_Proteogen No. 1._--Have used Plantex in four
cases, with good results in each case. One of them his father, an
elderly man.--April 25, 1918.
LOBAR PNEUMONIA:--_Proteogen No. 12._--The only case I have used
Proteogen No. 12, was a man who had Lobar Pneumonia of left lung
following Influenza. After crisis came, patient continued to have
slight rise in temperature, cough, and after using 10 doses of your
Proteogen No. 12, temperature was normal, cough very much better,
patient began to take on flesh and is still improving.--December
26, 1918.
TUBERCULOSIS:--_Proteogen No. 3._--The Doctor writes: The Proteogen
No. 3 sent me worked wonders in my patient. The case came under my
care when he was too far gone for anything to benefit him a great
deal, but the Proteogen did for him more than anyone could have
expected, yet he died leaving me with a few ampoules to try on the
next patient.--September 20, 1918.
GONORRHEAL CYSTITIS:--_Proteogen No. 11._--My patient has taken
two boxes of your Proteogen No. 11 given for gonorrheal cystitis
of probably two years’ standing and at this writing I consider
her almost, if not entirely, cured which I think speaks very
highly of your remedy. I expect to use more of your preparations
in the future.--April 12, 1919. [This testimonial, either by
clerical error, or because the results were considered remarkable,
was repeated elsewhere in the material submitted by the Merrell
Company.]
ACUTE GONORRHEA:--_Proteogen No. 11._--Mr. A. E. R., age 65, weight
140 pounds. First attack. Had had no previous treatment. Came to me
January 2, 1919. Had discharge, all acute symptoms, burning, etc.
Gave seventeen injections of Proteogen No. 11, also mild antiseptic
urethral wash. Discharged on February 15, 1919, clinically
cured.--April 11, 1919.
EPITHELIOMA OF BUTTOCK.--_Proteogen No. 1._--I used Proteogen No.
1 on an epithelioma of buttock some six months ago with favorable
results and no return of symptoms as yet.--April 13, 1919.
It is obvious that the Proteogen preparations are in conflict with
Rules 1, 6 and 10, and should not be admitted to “New and Nonofficial
Remedies.” It is recommended that the previous action of the
Council be allowed to stand and that publication of both reports be
authorized.--(_From The Journal A. M. A., July 12, 1919_)
“ARSENOVEN S. S.” AND “ARSENO-METH-HYD”
Report of the Council on Pharmacy and Chemistry
The Council authorizes publication of the following report. This report
declares Arsenoven S. S. of the S. S. Products Company and Solution of
Arsenic and Mercury (formerly called Arseno-Meth-Hyd) of the New York
Intravenous Laboratory, inadmissible to New and Nonofficial Remedies.
The Council takes this opportunity to repeat its warning against the
abuses--often dangerous--to which patients are frequently subjected
when “intravenous therapy” is employed.
W. A. Puckner, Secretary.
Because of inquiries received, the Council took up the consideration of
Arsenoven S. S. and Arseno-Meth-Hyd (now sold as Solution of Arsenic
and Mercury). The preparations having been referred to a committee for
consideration, this committee reported:
ARSENOVEN S. S.
“Arsenoven S. S.” is a preparation put out by the S. S. Products
Company, Philadelphia. The claims are made that it is “a simplified
office treatment for syphilis” and is “a combination of arsenic and
mercury for office use, offering maximum efficiency, safety and
convenience.” According to the company, “Arsenoven S. S.” contains
Dimethylarsenin 15.4 grains, Mercury biniodid 1/10 grain, Sodium iodid
1/2 grain. With regard to the identity of “dimethylarsenin” the company
claims: “This product is a compound of cacodylic acid similar to
sodium cacodylate but with a more pronounced therapeutic action.” The
committee recommends to the Council that “Arsenoven S. S.” be declared
inadmissible to New and Nonofficial Remedies because of unwarranted
therapeutic claims.
ARSENO-METH-HYD
“Arseno-Meth-Hyd,” is sold by the New York Intravenous Laboratory,
New York City, for the treatment of syphilis. It comes in three
dosages, 2 gm., 1.5 gm., and 0.7 gm., respectively. The claim is made
that “Arseno-Meth-Hyd 2 gm.” contains “2 gm. (31 grains) of Sodium
Dimethylarsenate (Cacodylate), U. S. P.. and Mercury Iodid 5 mg. (1/12
grain)” in 5 c.c. of solution. Physicians are told:
“In primary and early secondary case administer Arseno-Meth-Hyd
2 gm. every sixth day and Mercury Oxycyanide .008 (1/8 grain)
intravenously between each injection.”
“In Tertiary cases and those of long standing alternate with
intravenous injection of Sodium Iodid 2 gm.”
The following claims are made for the alleged effectiveness and safety
of the cacodylate:
“This methyl compound of arsenic has come into almost universal use
for syphilis. On account of lack of toxicity an aggressive routine
can be carried on. The simple technic and absence of reactions
make it most desirable for the regular practitioner. This large
dose gives more uniform results both as healing manifestations and
negative Wassermann’s.”
“Much discussion has surrounded the use of Methyl Compounds of
Arsenic and it has been demonstrated beyond doubt that Cacodylate
of Soda proves an effective remedy for syphilis provided that it is
properly administered.” [sic]
“The low toxicity of this Methyl compound of arsenic is remarkable.
It is contraindicated only where a decided idiosyncrasy for even
small doses of arsenic exists.”
These statements are essentially false and misleading. Cacodylate has
_not_ come into universal use in the treatment of syphilis, nor has
its usefulness been “demonstrated beyond doubt.” On the contrary,
H. N. Cole (The Journal, Dec. 30, 1916, p. 2012) has shown that doses
so large as to produce renal injury were almost totally ineffective
against syphilis. Obviously, “effective doses” if such exist, are not
harmless. The dosage advised for Arseno-Meth-Hyd may not produce acute
toxic symptoms; nevertheless smaller doses have produced nephritic
phenomena. The “Arseno-Meth-Hyd” treatment includes the intravenous
injection of about 1/4 grain of a mercury salt. Although this is less
than the usual dose (about 1 grain per week), the mercury is probably
more effective than the cacodylate.
The committee recommends to the Council that, because of the
unwarranted therapeutic claims, “Arseno-Meth-Hyd” be held inadmissible
to New and Nonofficial Remedies.
The Council adopted both reports of the committee and declared
“Arsenoven S. S.” and “Solution of Arsenic and Mercury”
(“Arseno-Meth-Hyd”) inadmissible to New and Nonofficial Remedies.
The committee’s reports on these two products impel the Council
again to call attention to the undesirable and dangerous abuses to
which “Intravenous Therapy” lends itself. There is a distinct field
for the intravenous administration of drugs in those cases in which
immediate drug action is necessary, or when the medicament is likely
to be changed if absorbed through the ordinary channels. Unless such
indications exist, however, intravenous administration involves not
only inconvenience and expense to the patient, but what is more
important, unnecessary danger. The fact that indiscriminate intravenous
administration is peculiarly profitable to certain manufacturing houses
makes it all the more necessary for the medical profession to be on its
guard in this matter.
In this connection it is well worth while to quote the closing
paragraph from an editorial on “Intravenous Therapy” that appeared in
The Journal, Nov. 11, 1916. It is as true today as when it appeared:
“Intravenous therapy will be most securely advanced if its employment
is restricted to such well defined fields. [As those mentioned above.]
These fields can be satisfactorily determined only by a scientific
pharmacologic study of the action of these drugs when so administered
in animals, as well as in man, under conditions in which the results
are carefully controlled. The intravenous method is an impressive one,
approaching in preparation almost to that which goes with a surgical
operation. The patient is usually interested and impressed by this
new, and, to him, mysterious method. There is a psychic element in his
reaction to the injection which is not a factor in his reaction to the
same drug when given by mouth. The intravenous injection of a complex
mixture would appear to be particularly reprehensible. Little is known,
as has been stated, of the results to be expected from intravenous
therapy, even with simple substances. The use of complex mixtures will
without doubt react against the proper use of the method.”
After the report on Arseno-Meth-Hyd had been presented to the Council,
a letter was received from the New York Intravenous Laboratory
announcing that the preparation “Arseno-Meth-Hyd” was now called
“Solution of Arsenic and Mercury” and expressing a desire to have its
products accepted for inclusion in New and Nonofficial Remedies. In
view of this letter, the committee’s report on “Arseno-Meth-Hyd” and
the Council’s protest against promiscuous intravenous therapy were
sent the New York Intravenous Laboratory for consideration.
The reply of the New York Intravenous Laboratory contained nothing
which permitted a revision of the preceding report. The change of the
name of “Arseno-Meth-Hyd” to “Solution of Arsenic and Mercury” means
little as the name still does not disclose the important fact that the
arsenic is present as sodium cacodylate, nor does it tell the character
of the mercury compound. The Council voted that “Solution of Arsenic
and Mercury” and “Arsenoven S. S.” be declared inadmissible to New and
Nonofficial Remedies because the therapeutic claims advanced for them
are unwarranted (Rule 6) and because the names of these pharmaceutical
preparations are not descriptive of their composition (Rule 8).
In filing its reply with the Council, the New York Intravenous
Laboratory announced that that document would be circulated to the
medical profession. This is of course the firm’s privilege. The Council
notes, however, with interest, that the reply is devoted almost
entirely to points which were not raised by the Council and that it
fails to discuss the objections which were actually made.
The reply constantly confuses the efficiency of cacodylate in anemia
and in syphilis. The Council’s report on “Arseno-Meth-Hyd” does not
discuss or even touch on the question of cacodylates in anemia. It
is confined to a discussion of the disappointing results obtained
with cacodylates as such (i. e., without mercury) in the treatment
of syphilis. This attempt on the part of the New York Intravenous
Laboratory to confuse the issue and to attribute to the Council
an opinion that it has never stated or held is an inexcusable
misrepresentation. The company in its reply said:
“We believe that you have previously stated that a solution
cacodylate of soda possesses no more action than so much water. In
other words, it was inert. Now you try to show that it produces
renal injury.”
The Council has never declared that cacodylates are inert. In the
report it is merely stated “that doses so large as to produce renal
injury were almost totally ineffective against syphilis.” Neither
has the Council stated that cacodylate is “peculiarly dangerous.” In
fact the absolute toxicity of cacodylates is low but Cole’s results
were quoted as a caution that “effective” doses are not harmless. A
great portion of the remainder of the reply is devoted to disparaging
arsphenamin--a product that is not involved in this action of the
Council, and one about which the physician is amply informed.
Amongst other wholly extraneous matters, the firm’s “reply” tried to
resurrect the pepsin pancreatin controversy. This also has nothing
to do with the efficiency or harmlessness of sodium cacodylate. In
order to dispose of the matter, however, it may be pointed out that
the implications are entirely misleading. The work which is quoted
against the Council was undertaken by the Council itself, to clarify
obscurities in the older data. The outcome of these new investigations
showed the essential correctness of the deductions from the older work,
namely, that pancreatin is destroyed by pepsin-hydrochloric acid. Dr.
Long’s work to which the firm’s reply evidently refers, showed that
under favorable conditions, namely, when protected by an excess of
protein, some trypsin may escape destruction in the stomach; but it
fully confirmed the original conclusion that pepsin and pancreatin
mixtures as ordinarily administered are practically worthless (J. H.
Long, _Jour. Amer. Pharmaco. Assoc._, Sept. 19, 1917).
As regards the editorial on intravenous therapy, a concession may be
made the New York Intravenous Laboratory: intravenous injections are no
longer quite as “impressive” as in 1916, but that does not alter the
fact that they should be used only when a distinct advantage is to be
gained.--(_From The Journal A. M. A., Aug. 2, 1919_)
HORMOTONE AND HORMOTONE WITHOUT POST-PITUITARY
Report of the Council on Pharmacy and Chemistry.
“Hormotone,” of the G. W. Carnrick Company, is advertised as “A
pluriglandular tonic for asthenic conditions.” “Hormotone Without
Post-Pituitary” is recommended for use “in neurasthenic conditions
associated with high blood pressure.” These preparations are sold in
the form of tablets for oral administration. The Council declares these
preparations inadmissible to New and Nonofficial Remedies because: (1)
Their composition is semisecret (Rule 1); (2) the therapeutic claims
are unwarranted (Rule 6); (3) they are sold under names not descriptive
of their composition but suggestive of indiscriminate use as “tonics”
(Rule 8); (4) in the light of our present knowledge the routine
administration of polyglandular mixtures is irrational (Rule 10). In
explanation of this action, the Council authorized publication of the
report which appears below.
W. A. Puckner, Secretary.
Each tablet of “Hormotone” (G. W. Carnrick Co., New York City) is said
to contain 1/10 grain of desiccated thyroid and 1/20 grain of entire
pituitary, together with the hormones of the ovary and testes--the
amounts and the form in which the latter are supposed to be present are
not given. From this it will be seen that the only definite information
given to the medical profession regarding the composition of Hormotone
is that it is a weak thyroid and a still weaker pituitary preparation.
What results can be anticipated from one or two tablets three times
daily (the recommended dose of Hormotone) each containing 1/10 grain
of thyroid and 1/20 grain entire pituitary? Such doses of thyroid
may, of course, have a beneficial action in a limited number of cases
of myxedema and cretinism. An extract of the posterior lobe of the
pituitary (Liquor Hypophysis, U. S. P., for example) will, _when
injected subcutaneously or intramuscularly_, have a pronounced effect
on the parturient uterus; its action on certain other forms of smooth
muscle will be much less certain. But the _oral administration_ (for
which Hormotone is recommended) of the posterior lobe of the pituitary
has not been shown to have any such effect. The use of the anterior
lobe in doses of 1 to 4 grains (doses very many times larger than those
recommended for the entire gland in Hormotone) is in the experimental
stage and its only probable value seems to be in those cases of known
gland deficiency.
As to the other alleged ingredients of Hormotone--hormones of the ovary
and testes, amounts not stated: all physicians know the uncertainties
attending the use of ovarian preparations and the serious question as
to whether testicular extracts have any therapeutic value. Whatever may
be the physicians views as to the probable therapeutic value of these
organs, the first thing he desires to know is how much of the substance
he is giving and from what part of the gland it is obtained.
So much for the facts; yet the physician is asked to jump from this
region of solid fact into a sea of hypothesis; to believe that
small amounts of the well-known drugs thyroid and pituitary, plus
an unknown amount of unknown hormones of the testes and ovary are
of great value in conditions that in themselves are often purely
hypothetical. He is asked to believe that this combination has
virtues in such conditions as “hypofunction of the adrenal system,”
neurasthenia, the “fatigue syndrome,” amenorrhea, dysmenorrhea,
“natural and artificial menopause,” sexual neuroses, cold extremities,
cardiac asthenia, low blood pressure, infantilism, sterility,
melancholic conditions, obesity, anorexia, anemia, slow metabolism,
constipation, psychasthenia, lowered virility and the sexual neuroses
of the unmarried, hysteria following functional exhaustion of the
nerve centers, frigidity, etc., etc., especially if he guesses that
the trouble is due to a “pluriglandular disturbance,” “glandular
hypofunction,” an “adreno-pituitary deficiency,” suboxidation, etc.
The physician is invited to use Hormotone because, among other reasons,
each alleged constituent is said to be “in physiologic sympathy and
therapeutic harmony with the others,” and further, because:
“Pluriglandular therapy has the endorsement of high authorities,
is both logical and effective and Hormotone is a splendid example
of it. It will be seen at its best where the patient lacks snap
and vim and vigor. Asthenic conditions necessarily indicate
hypofunction of the adrenal system ...” etc.
“The use of gland extracts in the treatment of aplasias of the
pluriglandular system has become an established therapeutic measure
of miraculous potency (Bayard Holmes: The Internal Secretory
Glands, _Lancet-Clinic_, Sept. 19, 1914).”
The G. W. Carnrick Company also advertises a “Hormotone Without
Post-Pituitary,” each tablet of which is said to contain 1/10 grain
desiccated thyroid, and to “present” “hormone bearing extracts of
thyroid, anterior pituitary, ovary, and testes.” This product is just
as irrational as “Hormotone.”--(_From The Journal A. M. A., Aug. 16,
1919_)
FORMALDEHYDE LOZENGES
Report of the Council on Pharmacy and Chemistry
The Council has voted Hex-Iodin (Daggett and Miller Co., Inc.,
Providence, R. I.), Formitol Tablets (E. L. Patch Co., Boston), and
Cin-U-Form Lozenges (McKesson and Robbins, New York City) inadmissible
to New and Nonofficial Remedies, and authorized publication of the
report which appears below.
W. A. Puckner, Secretary.
Some years ago, the Council published (The Journal A. M. A., Aug.
28, 1915, p. 816) a report on Formamint, a proprietary medicine
widely exploited as a peculiar chemical compound of sugar of milk and
formaldehyde. The formaldehyde was said to be liberated slowly by the
action of the saliva, and because of this liberation of formaldehyde,
Formamint was claimed to be a powerful germicide. Extravagant claims
were made for its curative and prophylactic effects. The Council found
that the therapeutic claims were grossly unwarranted and that its
exploitation to the public was a public danger.
During the recent epidemic of influenza, a variety of tablets or
lozenges were advertised, and are still being advertised, having
formaldehyde, in some form or other, as the nucleus around which
revolve the therapeutic claims. In some cases, the advertising clearly
indicates the character of the formaldehyde compound that is claimed
to be present; in others the statements are vague and indefinite or
misleading.
It is hardly necessary to remind physicians that the use of tablets
containing hexamethylenamin or other formaldehyde compounds can neither
cure respiratory infections, nor even confer protection against such
infections. To be effective, formaldehyde would need to be supplied
to the entire respiratory tract continuously for some time or else in
concentrations that would be distinctly irritant and damaging to the
tissues. Saliva-dissolved tablets, obviously cannot reach the nasal
or tracheal mucosae directly; and the application of quickly acting
concentrations of formaldehyde is out of the question. This altogether
aside from the fact that hexamethylenamin, the basis of some of these
tablets, does not liberate formaldehyde in the mouth, and for this
reason alone would be quite useless for this purpose! (See Hanzlik and
Collins, _Archives of Internal Medicine_, November, 1913.)
An inefficient antiseptic is more than merely useless; it is a menace
to public safety, in that it tends to lead to the neglect of rational
and effective protective measures. It therefore seems advisable for
the Council again to call the attention of physicians to the subject.
Accordingly, three specimens of these products were purchased and
examined in the Association’s Chemical Laboratory.
Hex-Iodin
Hex-Iodin (Hexamethylenetetramine and Iodum) Lozenges are manufactured
by Daggett and Miller Company, Inc., Providence, R. I. They weigh
15-1/2 grs. each, are sweetened and are flavored with mint or menthol.
The package and circulars do not contain a definite statement of
composition. The rather indefinite synonyms “Hexameth. and Iodine
Comp.” and “Hexamethylenetetramine and Iodum” suggest that the lozenges
contain hexamethylenamin and free iodin. The further statement that
they “contain the combined medicinal antiseptic and prophylactic
properties of Hexamethylenetetramine and Iodum” is also rather
indefinite. The therapeutic action claimed for the lozenges, however,
could only be produced by free iodin and by liberated formaldehyde.
It is unnecessary to discuss in detail the extravagant claims made
for these lozenges. The inefficiency of hexamethylenamin has already
been referred to; the limitations of iodin, free or combined, in
lozenge form, need not be discussed because the examination made in the
A. M. A. Chemical Laboratory showed that Hex-Iodin lozenges contained
no free iodin, and only traces of combined iodin. Neither formaldehyde
nor paraformaldehyde was present; hexamethylenamin was present but, the
lozenges being neutral no formaldehyde is generated in contact with
water or with the alkaline saliva.
Thus Hex-Iodin is shown to be worthless for the purpose for which it is
advertised. Of the two important ingredients said to be present, iodin
and hexamethylenamin, only traces could be found of the former while
the latter, as has been shown, is incapable of exerting any effect when
used as the manufacturers direct.
Formitol Tablets
These tablets are prepared by the E. L. Patch Co., Boston. Each tablet
weighs 13-1/2 grs. They have the odor of thymol or menthol and an acid
taste and reaction. They are, according to the label:
“For the throat and mouth. Soothing, Astringent, Antiseptic.
Rapidly destroys germs of infection, preventing and relieving sore
throat and mouth.”
In a circular, it is stated, that one of the qualities of Formitol:
“... is the generation of formaldehyde when in contact with water
or the saliva.”
“Besides generating formaldehyde, Formitol, Patch contains
astringent, demulcent and soothing ingredients which render the
combination unusually effective.”
A bacteriologic report is given in this circular in which it is stated
that, in 2-1/2 minutes one Formitol Tablet rendered sterile a plate
culture of a “characteristic throat micrococci.” The instructions
are to dissolve a tablet in the mouth, slowly, once an hour or a
half-tablet every half hour.
The A. M. A. Chemical Laboratory reported that Formitol Tablets
contained formaldehyde (or paraformaldehyde), and ammonium compound,
and some hexamethylenamin. It is probable that the formaldehyde (or
paraformaldehyde) was produced by the decomposition of hexamethylenamin
originally present in the tablets but decomposed by long contact with
the acid.[128]
[128] The E. L. Patch Company declares that “no hexamethylenamine
has ever been used in the manufacture of Formitol tablets,” and that
ammonium chloride and paraformaldehyde are among the ingredients used
in the manufacture of these tablets. The hexamethylenamine present
in the tablets, therefore, must have been produced by interaction of
the paraformaldehyde and ammonium chloride. This does not alter the
laboratory findings regarding the composition of the tablets, namely,
that they “contain formaldehyde (or paraformaldehyde), an ammonium
compound and some hexamethylenamine.”
These tablets differ from Hex-Iodin in that they really contain active
formaldehyde and, therefore, possibly produce antiseptic effect
in test-tube cultures. The conditions in the mouth, however, are
very different from those in the test-tube, since in the mouth the
formaldehyde would be immediately “bound” or absorbed. The claimed
absence of irritation indicates sufficiently the absence of efficient
quantities of formaldehyde under clinical conditions.
Cin-U-Form Lozenges
Cin-U-Form Lozenges, manufactured by McKesson and Robbins, New York
City, are marketed in bottles of 24 for 25 cents. They have a strong
odor of cinnamon, weigh 15-1/2 grs. each, and are acid in taste and
reaction. The label states that they contain:
“Cinnamon, Eucalyptus, Formaldehyde and Menthol--all powerful
germicides against Influenzal bacilli, but not injurious to the
system in this palatable form.”
A circular contains the same statement as to composition and claims
further that they:
“... help to prevent the infection of Spanish Influenza, Pneumonia,
Grip Colds and to guard against Sore Throat, Tonsillitis,
Pharyngitis, etc.”
The A. M. A. Chemical Laboratory reported that Cin-U-Form
Lozenges contained some formaldehyde (or paraformaldehyde) and no
hexamethylenamin. It is obvious that the mouth and throat cannot be
“disinfected” by these lozenges. They would be totally ineffective
against bacteria that enter through the nose; they cannot prevent
influenza, pneumonia, etc.--(_From The Journal A. M. A., Oct. 4, 1919_)
LAVORIS
Report of the Council on Pharmacy and Chemistry
Lavoris was considered by the Council in 1913, and its proprietors--the
Lavoris Chemical Company--were advised that the preparation was
inadmissible to New and Nonofficial Remedies because of conflict with
Rules 1, 4, 6, 8 and 10. No report was published at that time. As the
preparation is still widely advertised to physicians, the Council has
again examined Lavoris and authorized publication of the following
report.
W. A. Puckner, Secretary.
In recent years Lavoris has been widely advertised as “THE IDEAL ORAL
ANTISEPTIC,” particularly to the dental profession. A printed card
sent out by the Lavoris Chemical Company in 1913 read: “LAVORIS, the
Pyorrhea Remedy. The Original ZINC CHLORIDE Mouth Wash. One grain zinc
to each ounce.” The card also gave a “formula” to the effect that each
pint of Lavoris contained:
Zinc Chloride 1.040
Resorcin 0.520
Menthol 0.400
Saccharin 0.195
Formalin 0.195
Ol. Cassia Zeyl 0.780
Ol. Caryophyl 0.195
Advertisements now appearing in medical journals repeat the older
“formula” except that resorcin is omitted. The formula while seemingly
frank and open is in reality indefinite and misleading in that no
denomination of weight is given for the various constituents. It is
uncertain, for example, if the figures in the formula are intended to
represent grains, grams or percentages of the several constituents.
In view of the indefinite statement of composition, a chemical
examination of Lavoris was undertaken in the A. M. A. Chemical
Laboratory. The report of the laboratory follows:
_Zinc._--This was determined electrolytically. Fifty c.c. gave
0.026 gm. zinc and 100 c.c. gave 0.0531 gm. zinc. The average is
0.0526 gm. zinc in 100 c.c. This is equivalent to 0.1102 gm. anhydrous
zinc chlorid in 100 c.c.
_Chlorid._--After decolorizing some of Lavoris with chlorid-free animal
charcoal, the chlorid was determined by the Volhard method. Twenty-five
c.c. Lavoris required 4.328 c.c. tenth-normal silver nitrate solution
equivalent to 0.01535 gm. chlorid (chloridion) or 0.0614 gm. in
100 c.c. A second 25 c.c. of Lavoris required 4.112 gm. tenth-normal
silver nitrate solution equivalent to 0.01458 gm. chlorid (chloridion)
or 0.05832 gm. in 100 c.c. Average is 0.05985 gm. This is equivalent
to 0.1150 gm. zinc chlorid in 100 c.c. This agrees closely with the
foregoing zinc determination.
_Resorcin._--The method of the U. S. Pharmacopeia was used. The total
bromin absorption of 25 c.c. Lavoris was 3.68 c.c. tenth-normal
bromin solution. This would be equivalent to 0.00675 gm. resorcin
in 25 c.c. or 0.02700 gm. in 100 c.c. In a duplicate test, 25 c.c.
Lavoris required 3.8 c.c. tenth-normal bromin solution equivalent to
0.00697 gm. resorcin or 0.02788 gm. in 100 c.c. Since oil of cinnamon
absorbs bromin, 50 c.c. of Lavoris was boiled until very little or
no odor of the oil was noted, keeping the volume nearly constant by
adding a little water from time to time, and the bromin absorption then
taken. In one experiment, 0.36 c.c. of tenth-normal bromin solution was
consumed, and in a duplicate no bromin was absorbed. This shows the
absence of resorcin.
_Residue._--On evaporating 25 c.c. Lavoris on a steam bath and
subsequent drying of the residue at 100 C., 0.0455 gm. of residue was
obtained. This is equivalent to 0.1820 gm. in 100 c.c.
_Saccharin._--Saccharin was detected in the residue and ether-extract
of the residue by its intense sweet taste when a little sodium
bicarbonate was added to it.
_Formaldehyd._--This could be detected by the Jarrison test. The color
was not very pronounced and the quantity of formaldehyd was small.
_Oil of Cinnamon._--The odor and taste of Lavoris is characteristic of
cinnamon.
_Menthol and Oil of Cloves._--The odor of menthol and of oil of cloves
could not be detected, but no tests were made to demonstrate their
presence.
The analysis thus indicates that the Lavoris of today contains no
resorcin but does contain a small amount of formaldehyd, a little
saccharin, and oil of cinnamon (menthol and oil of cloves could not be
detected by the odor, but were not tested for). The analysis showed
that the principal constituent of Lavoris is zinc chlorid, of which
there is about 0.1 gm. per 100 c.c. (about 1/2 grain to the ounce).
The amount of zinc chlorid given in the published formula, i. e.,
1.04, is meaningless because the unit of weight or measure is not
given; furthermore, the analysis shows that it is inaccurate for any
unit of weight that might be assumed from the published figures. Since
the amount of the most active medicinal ingredient is both indefinite
and inaccurate, the composition of the preparation is essentially
secret. Lavoris is indirectly advertised to the public by having
included in the package a circular giving a list of diseases for which
the preparation was recommended. The combination of zinc chlorid,
formaldehyd and oil of cinnamon (assuming the menthol and oil of cloves
to be present as flavors) in a mixture is irrational and likely to lead
its users to ascribe a false and exaggerated value to the preparation.
The name is objectionable in that it does not indicate the composition
of the potent ingredients of the mixture, but instead suggests its use
as a mouth wash.
From a standpoint of public safety, the most serious objection to
Lavoris, however, lies in the many unwarranted therapeutic claims
and suggestions. It is generally held that zinc chlorid solutions
which possess a strength of from 1 to 200 up to 1 to 500 exercise a
weak antiseptic action. The strength of zinc chlorid in Lavoris is
approximately 1 to 1,000. The directions for its use recommend that
Lavoris should be diluted. A dilution of 1 to 4 is recommended for a
variety of mouth conditions while for cystitis irrigations and as a
vaginal douche, it is recommended that one tablespoonful be added to
a quart of warm water or salt solution. The strength of zinc chlorid
in the last suggested dilution would approximate 1 to 64,000. It is
evident that no antiseptic action could be expected from such dilutions.
The recommendation that diluted Lavoris be used for the treatment
of coryza, nasal catarrh, hay fever, inflamed eyes, hemorrhoids and
leucorrhea is objectionable and irrational. Especially dangerous is
the recommendation that members of a family exposed to diphtheria
or scarlet fever should use Lavoris freely as a preventive. Such
recommendations can but give a false sense of security and lead to the
neglect of proved methods for preventing the spread of these diseases.
Equally unwarranted is the recommendation that in gonorrhea one
teaspoonful of Lavoris to eight of warm water be used with a blunt end
syringe.
The use of Lavoris as recommended would not only prove valueless in
many instances but might lead to serious consequences because really
valuable methods of prevention or treatment might be neglected. For
these reasons the preparation is in conflict with Rule 6.
The Council declared Lavoris ineligible for New and Nonofficial
Remedies.--(_From The Journal A. M. A., Nov. 1, 1919_)
MEDINAL
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on
Medinal (Schering and Glatz, Inc.).
W. A. Puckner, Secretary.
Medinal is a proprietary name applied to barbital sodium (sodium
diethylbarbiturate) the sodium salt of barbital (diethylbarbituric
acid). The latter was first introduced as Veronal.
Medinal was deleted from New and Nonofficial Remedies in 1916 because
the advertising issued by Schering and Glatz (who then acted as
agents for Chemische Fabrik auf Actien vorm. E. Schering, the German
manufacturer) contained misleading and unwarranted therapeutic claims.
The Council did not publish its report because by the time the report
was ready for publication the product was practically off the American
market, and it was hoped that when Medinal again became available,
Schering and Glatz would revise the claims and thus permit its
reacceptance.
Medinal, said to be manufactured in the United States, is now marketed
by Schering and Glatz, Inc. In October, 1918, the firm sent to the
Council a typewritten copy of a proposed circular for Medinal. The firm
was informed that this leaflet was subject to the objections that had
been raised when Medinal was deleted from New and Nonofficial Remedies.
In April, 1919, the firm submitted a printed circular which it was
sending out. This contained numerous misleading statements, among them,
these:
“MEDINAL removes its [Diethylbarbituric acid] one objectionable
feature--insufficient solubility--and thus fulfills the three
prerequisites of a truly rational hypnotic: Quick absorption,
insuring prompt action, rapid and complete excretion, affording
protection from cumulative toxic after effects, and the choice of
rectal and subcutaneous administration.”
There is no justification for the claim that diethylbarbituric acid
(barbital) has only one objectionable feature and that a minor matter
of “insufficient solubility.” The Council has called the attention of
Schering and Glatz, Inc., to the fact that the difference in the time
of absorption between Medinal (barbital sodium) and barbital is, at the
most, but one of minutes and that there is no evidence that Medinal is
excreted more rapidly than barbital. Hence the claims that the danger
of toxic side-actions and that cumulative after-effects are avoided in
this product, are wholly unwarranted.
It is also claimed, and the claim is unsupported by satisfactory
evidence, that Medinal is useful in the insomnia of tuberculosis in
which condition it is said to have a double advantage owing to its
favorable effects on the night-sweats. It is claimed that Medinal
is used in the withdrawal treatment of morphin addiction with great
success; there is no evidence that Medinal has any special usefulness
in this treatment of the morphin habit. It is claimed further that
success has been reported with Medinal in the treatment of whooping
cough. The Council knows of no satisfactory evidence to show that
Medinal is of special value in whooping cough; on the contrary, it is
capable of doing a great deal of harm. The recommendations that Medinal
be used for the control of labor pains and in acute neuralgic pains
that resist other forms of treatment are wholly unwarranted as the
value of the drug in such conditions is inherently improbable and until
satisfactory evidence in support of them is forthcoming, must be deemed
misleading.--(_From The Journal A. M. A., Nov. 15, 1919_)
OMISSION OF COTARNIN SALTS (STYPTICIN AND STYPTOL) FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
Salts of the base cotarnin have been used as local and systemic
hemostatics. The hydrochlorid was first introduced as “Stypticin,”
and is now in the pharmacopeia as cotarnin hydrochlorid
(_Cotarninae Hydrochloridum, U. S. P._). The phthallic acid salt of
cotarnin--cotarnin phthallate--was introduced as “Styptol.” Both
Stypticin and Styptol were admitted to New and Nonofficial Remedies. In
1918 the Council voted to omit Stypticin because the former American
agents were no longer offering it for sale. Styptol was retained and is
described in N. N. R., 1919.
As was pointed out in the description (N. N. R., 1918), the evidence
for the usefulness of the cotarnin salts has been contradictory and
unsatisfactory; but since the available data against the efficiency
were at least equally unreliable, the Council deemed it best to retain
them in N. N. R. pending a thorough investigation of the subject. This
was undertaken by P. J. Hanzlik, at the suggestion of the Therapeutic
Research Committee of the Council.
A reliable judgment of hemostatic efficiency can be formed only on a
basis of strictly controlled conditions, which can best be furnished in
the laboratory. Hanzlik repeated the principal experiments published
by previous investigators, and applied a number of new or improved
methods. The results (published in the _Journal of Pharmacology
and Experimental Therapeutics_ =10=:523, 1918; =12=:71, 1919) show the
following:
_Direct Application to Wounds._--The widely quoted results of the
gynecologist K. Abel, on the footpad of cats, were found to be quite
unreliable. When the experiment is properly controlled, the results
are either negative or the bleeding may be increased. Quantitative
experiments on wounds of the footpad of dogs showed that cotarnin
invariably _increased_ the bleeding. Equally negative or unfavorable
results were obtained with wounds to the comb of roosters, and to the
liver and spleen.
_Direct Action on Vessels._--The results of perfusion experiments were
variable, but, in general, showed a vasodilation action instead of
constriction. This holds true also of the uterine vessels. The vessels
in the living animal (rabbit’s ear) were also unaffected.
_Systemic Administration._--The bleeding from an irrigated wound was
not modified directly by intravenous injection of cotarnin salts, but
varied merely with the state of the blood pressure.
The evidence for the inefficiency of cotarnin salts as hemostatics
seemed so conclusive as to warrant the Council in rescinding the
acceptance of Styptol, and directing the omission of the general
article on cotarnin salts and the description of Styptol from New and
Nonofficial Remedies.--(_From The Journal A. M. A., Nov. 22, 1919_)
MICAJAH’S WAFERS AND MICAJAH’S SUPPOSITORIES
Report of the Council on Pharmacy and Chemistry
“Micajah’s Medicated Wafers” and “Micajah’s Suppositories,” sold by
Micajah & Co., Warren, Pa., are declared inadmissible to “New and
Nonofficial Remedies” because (1) their composition is essentially
secret (Rule 1); (2) name of neither of these mixtures is indicative
of its composition (Rule 8); (3) of exaggerated and unwarranted
therapeutic claims (Rule 6), and (4) the therapeutic advice which
accompanies the trade packages constitutes an indirect advertisement to
the public (Rule 4).
W. A. Puckner, Secretary.
Micajah’s Medicated Wafers (formerly called “Micajah’s Medicated
Uterine Wafers”) were analyzed in the A. M. A. Chemical Laboratory in
1910. They were found to consist essentially of dried (“burnt”) alum,
boric acid and borax, in approximately the following proportions:
Alum, dried 59.86 per cent.
Borax, dried 15.62 per cent.
Boric acid 5.67 per cent.
Water of hydration 18.85 per cent.
There are a number of drugs that are more or less effective in the
treatment of local lesions of mucous membranes and the skin. They
are classed as astringents. Among these are included alum, borax
and boric acid. Every physician has used them. To say that a wafer
consists of alum, borax and boric acid inspires but little awe. But
there is something much more mysterious and impressive in declaring
that a wafer “consists of an astringent and antiseptic base, in which
are incorporated certain medicaments which both locally and after
absorption, contribute to the astringent, antiphlogistic, depletive,
soothing and healing action of the product.” This gives the impression
that some powerful and almost incomprehensible factors are at work.
Yet, after all is said and done, the substances contained in Micajah’s
Medicated Wafers are just the homely old alum, boric acid and borax.
In addition to “Micajah’s Medicated Wafers,” Micajah & Co. also put out
“Micajah’s Suppositories for Hemorrhoids.” These have been examined in
the A. M. A. Chemical Laboratory and, like the “Medicated Wafers” have
been found to contain alum, boric acid and borax--and these substances
practically alone--incorporated in cocoa butter. The company claims
that “to these have been added Ammonii Ichthyosulphonate, Balsam of
Peru, Ext. Belladonae.” The A. M. A. chemists report, however, that if
extract of belladonna is present at all it is in amounts too small to
be detected by the method commonly employed in the chemical examination
of alkaloidal drugs. The chemists report further that while ammonium
ichthyosulphonate and balsam of Peru both have a decided odor and are
dark in color, the suppositories have but little color and the odor of
the cocoa butter that forms their base is not covered by these drugs;
obviously, therefore, if ammonium ichthyosulphonate and balsam of Peru
are present at all it is in amounts utterly insufficient to exert any
therapeutic effect.
It would be hard to find better examples of mischievous proprietary
medicines than these two products of the Micajah Company. “Twins
of Efficiency,” they are called in an advertising pamphlet. The
composition is not stated. A physician using the “twins” does so
absolutely in the dark. To him they are secret preparations. He is
encouraged to use them in a great variety of conditions in which other
drugs are much more useful. Inevitably, physicians using them will be
likely to overlook, or pass over, new growths, specific infections and
diseases that require radical remedial measures.
In addition to misleading and exaggerated claims, there is a reference
to a report from the usual “well-known and reliable bacteriological
laboratory.” The excerpts published from this report of an unnamed
laboratory are sufficiently vague to incriminate no one.
From time to time it is worth while to emphasize facts regarding
proprietary medicines that while obvious are sometimes forgotten. For
this reason attention is directed to Micajah’s Uterine Wafers and
Micajah’s Suppositories.--(_From The Journal A. M. A., Nov. 29, 1919_)
ALKALITHIA
Report of the Council on Pharmacy and Chemistry
Alkalithia was introduced at a time when it was believed that the
administration of lithium salts served to remove uric acid from the
system. The product was considered by the Council in 1906, and found
ineligible for New and Nonofficial Remedies. No report, however, was
published at that time.
Because of inquiries received, the Council examined the current claims
for Alkalithia, and authorized publication of the report which appears
below.
W. A. Puckner, Secretary.
Keasbey and Mattison Company’s Effervescent Alkalithia is sold with the
following statement of composition:
“Each dose or heaping teaspoonful contains 1 grain of Caffeine, 10
grains each of Bi-carbonates of soda and potash, and 5 grains of
Carbonate of Lithia.”
The A. M. A. Chemical Laboratory reports that Alkalithia is an
effervescent mixture which contains alkaline carbonates and
bicarbonates together with caffein, free tartaric acid and free citric
acid. The major portion of the alkali carbonates and bicarbonates
is converted into citrates and tartrates when the preparation is
dissolved in water--as is done before it is taken. An excess of alkali
is present, however, as the solution has an alkaline reaction. Each
“heaping teaspoonful” (which was found to be about 4.85 Gm.) contains
about 0.044 Gm. of caffein (the manufacturers claim 0.0648 Gm. per
heaping teaspoonful). As taken, Alkalithia, therefore, represents
caffein in a solution of alkali tartrate, citrate and bicarbonate
containing free carbonic acid. If it is assumed that all of the
tartrate and citrate in Alkalithia is converted into carbonate in
the organism, a “heaping teaspoonful” of Alkalithia would represent
about 2.9 Gm. of sodium bicarbonate. This assumption is, however, not
correct, for it is known that tartrates are not completely converted
into carbonates in the organism.
According to the label on the bottle, this mixture of caffein and
alkali salts is “a common sense remedy for the relief and treatment
of conditions dependent upon perverted metabolism as manifested by
neuralgic, rheumatic, cardiac and renal symptoms.” Wrapped with a trade
package is a circular in which is discussed the “uric acid diathesis”
as “a cause of Rheumatism in its various forms, Calculus, Gravel and
Inflammation of the Bladder and Kidneys, Asthma, Hay Fever, Catarrh,
Quinsy and Bronchitis, Eczema, Hives, Itching and Burning of the Skin,
Palpitation of the Heart and Cold Hands and Feet, Dizziness, Mental
Depression, Melancholia, Neuralgia, Chorea, Hysteria, Numbness and a
great variety of purely nervous symptoms.” The arguments for the use
of Alkalithia as “a safe and scientific treatment for the uric acid
diathesis” found in the circular constitute an indirect appeal to the
laity (conflict with Rule 4).
In the circular matter sent direct to the physicians, Keasbey and
Mattison claim that in rheumatism, Alkalithia is prescribed by the
medical profession more often than any other remedy. The claim is made
that, “In five minutes the urine will be discolorized and analysis will
show it to be loaded with urates.” The manufacturers further assert:
“You can change the character of the urinary secretion in a few
minutes completely” by Alkalithia, and “In nine cases out of
ten, when the doctor prescribes ‘Alkalithia’ his patient greatly
improves, or gets well.”
The firm advises that “Renal Insufficiency” be determined by the old
method of multiplying the ounces of urine in twenty-four hours by the
last two numbers of the specific gravity, adding 10, which gives the
number of grains of solids excreted in the twenty-four hours. If this
is low, no matter what the cause, they advise Alkalithia, “that ideal
eliminant.”
The Council declared Alkalithia inadmissible to New and Nonofficial
Remedies because the claims made on the label and the circular
accompanying the trade package lead the public to its detriment to
depend on this preparation (Rule 4); and because the therapeutic claims
are unwarranted (Rule 6).--(_From Reports of Council on Pharmacy and
Chemistry, 1919, p. 65_)
ARHOVIN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Arhovin is a solution of dephenylamine, thymol benzoate and ethyl
benzoate, marketed by Schering and Glatz, Inc. It was omitted from
New and Nonofficial Remedies because the therapeutic claims made for
the preparation were unwarranted and because the firm had refused to
discontinue the distribution of the advertising which contained the
objectionable claims prior to Jan. 1, 1919. When the report which
appears below explaining the dismissal was submitted to Schering and
Glatz, Inc., the firm again promised a revision of its advertising,
but refused discontinuance of the objectionable circular before Jan.
1, 1920. Since Arhovin is still marketed with unwarranted therapeutic
claims, the Council has authorized publication of this report.
W. A. Puckner, Secretary.
The attention of the firm Schering and Glatz, Inc., was called to
misleading statements in its booklet for Arhovin in 1915, and in 1918
the firm was informed that unless the misleading statements were
withdrawn before Jan. 1, 1919, Arhovin would be omitted from New and
Nonofficial Remedies.
The following quotations are taken from the circular in question, and
illustrate the character of the claims to which objection was made:
“Striking also is the antiphlogistic and anesthetic effect
of Arhovin on the inflamed mucosae, an effect which, as all
authorities agree, is far greater than that of all other internal
anti-gonorrheaics.”
“Under its influence vesical and prostatic complications,
gonorrheal arthritis, endocarditis, etc., are rarely incurred.”
References to the indexes of leading textbooks, including those
of Meyer and Gottlieb, Cushny, Sollman and Bastedo, fails to show
that Arhovin is so much as mentioned by those authors; hence, it is
obviously false to state, as is done in the first of the quotations
above, that all authors agree concerning the striking effects of
Arhovin.
Many of the statements are objectionable by reason of the actions
implied, rather than stated directly. The following are examples:
“Arhovin in Gonorrheal Infections of the Male Genito-Urinary
Organs. Anterior Urethritis. This is the class of cases in which
the most favorable results from Arhovin have been reported.”
“Posterior Urethritis.
“Here also the striking effects from Arhovin medication, both
in acute and chronic cases, are rapid decrease of discharge,
disappearance of gonococci from the secretion, and cessation of
subjective difficulties, such as strangury.”
While the firm did not agree to withdraw the objectionable advertising
before Jan. 1, 1919, which made necessary the omission of Arhovin from
New and Nonofficial Remedies, 1919, it did submit a proposed folder in
which the most objectionable of the claims are still made.
The following statement, which was in the proposed “folder” and is
included in an advertising pamphlet sent out during 1919, serves to
illustrate those points:
“Its action is three-fold:
“Strong antiseptic and bactericidal effect upon the urethral and
vesical mucosae, highly conducive to shortening and palliation of
the acute disease course.”
No evidence has been presented that Arhovin is capable of destroying
the gonococcus in the urethra, and consequently, the Council
declared the recommendation for the use of Arhovin in the treatment
of gonorrhea, by means of claims such as those just cited, is both
misleading and dangerous.--(_From Reports of Council on Pharmacy and
Chemistry, 1919, p. 66_)
CHLORON, CHLORAX AND NUMBER “3”
Report of the Council on Pharmacy and Chemistry
The report which appears below was sent to the Chlorine Products
Company, Inc., May 14, 1919. In reply to an inquiry sent the Chlorine
Products Company, July 8, the company wrote that it could send no reply
because the medical director was still in France. However, Chloron and
Chlorax are being advertised in medical journals; also essentially the
same advertising as that discussed in the report was recently received
by a physician from the Chlorine Products Company.
The preceding facts having been reported to the Council, publication of
the report was authorized.
W. A. Puckner, Secretary.
Chloron, Chlorax and Number “3” are preparations of essentially similar
composition put out by the Chlorine Products Company, Inc., New York.
Chloron
Chloron, according to the label, is “A stable CHLORINE remedy for the
reduction of inflammation, relief of pain and for all wounds, burns,
scalds and every description of sores except cancer and lupus.” Its
composition is given as:
“Free chlorine, 0.200 per cent.; calcium chloride, 0.190 per cent.;
mercurous chloride, 0.030 per cent.; lithium chloride, 0.035 per
cent.; calcium hydrate, 0.010 per cent.; water to 100 parts.”
The Council asked the manufacturers for further information in regard
to the composition or preparation of Chloron and received this reply:
“Chlorine gas is prepared in the usual way and purified and passed
into water until a saturated solution is made.
“Water to the extent of three times the volume of the chlorine
solution is used to dissolve the necessary amount of calcium
chloride, and the two solutions are mixed.
“The necessary amounts of Lithium and Mercurous Chloride are then
intimately mixed and made into solution. This solution is then
added to the above and the whole is agitated for some minutes.”
A specimen of Chloron was examined in the A. M. A. Chemical laboratory
and the chemists reported:
Qualitatively the presence of the following constituents was confirmed:
calcium, mercury, lithium, chlorid, free chlorin. The solution was
alkaline. Of course, the declaration that Chloron contains mercurous
chlorid (calomel) is obviously incorrect, as mercurous chlorid cannot
exist in a solution containing active (free) chlorin, but is oxidized
to mercuric chlorid (corrosive sublimate). As the solution was alkaline
in reaction, it seemed unlikely that all the active chlorin was present
in the free state, as declared on the label. Quantitative determination
of free chlorin and of total active (“available”) chlorin gave: free
chlorin, 0.036 gm. per hundred c.c.; total “available” chlorin,
0.330 gm. per hundred c.c., or 165 per cent. of the claimed amount.
A comparison of the information sent to the Council with the analytic
findings leads to the conclusion that Chloron is not of reliable
composition.
As evidence of the therapeutic value of Chloron, the following “case
reports” were submitted:
“In a case of second degree burn involving the most of one leg
from the middle of the calf down, CHLORON was the only dressing
used. The burn was a bad one and the patient in a rundown anaemic
condition, at no time was there any appearance of pus, the surface
looked clean and bright and the healing was accomplished with
practically no scar whatever. The burn was kept wet with the
solution by hourly applications day and night. The skin which has
grown on the wound is clear, healthy and firm.
In another case of Varicose veins of long standing, the result was
surprising. The patient told of two years vibrating from Hospital
to Hospital and getting no real relief. Each leg had large open
running sores, the only dressing used was wet compresses of this
solution. The pus disappeared at once, the wound began to cicatrise
from the edges and in two weeks the man was discharged from the
hospital practically cured.”
“CHLORON was recently tried at the ---- and ---- Hospital on cases
presenting ulcers and other sores which did not readily yield to
other methods, with good results, in fact were of an indolent type.
In these cases CHLORON proved very valuable.”
“I have used CHLORON on a series of cases (surgical) presenting pus
foci and I have found the application very beneficial and healing,
the pus early disappearing. In cases of Osteomyelitis, Suppurating
Arthritis, Cellulitis and Chronic Ulcers, CHLORON is particularly
valuable, its good effects quickly observed and the time of
restoration to health shortened.”
In the first case report, there is no evidence that Chloron is more
efficient in the treatment of burns than any other commonly used
procedure might have been. In the case of the varicose ulcers, while
there was some apparent benefit from Chloron, no credit is given to
rest and the general treatment which is known to be important in the
treatment of such conditions. The evidence in the other case reports is
quite inconclusive. Consideration of the “case reports” leads to the
conclusion that clinical evidence for the value of Chloron is lacking.
Attention should be called to the fact that the amount of active
chlorin, claimed to be present in Chloron as well as the amount found
by the association laboratory, is less than that considered effective
by Dakin, Dunham and others; seemingly in preparing Chloron no
attention has been paid to the degree of alkalinity, yet the importance
of this factor is now generally recognized.
Chloron fails to comply with the requirements for surgical solution of
chlorinated soda (N. N. R., 1919, p. 133), yet the manufacturers make
free use of the text of Dakin and Dunham’s Handbook of Antiseptics in
their advertising pamphlet. Thus:
From the Chloron pamphlet:
“This ideal antiseptic effects complete sterilization within
its sphere of action without causing any damage to the cells or
tissues. An important method of judging the injurious action of
antiseptics is to investigate their effects on the leucocytes. From
experiments _in vitro_ by Parry Morgan and _in vivo_ by Col. C. J.
Bond with the strength of antiseptics commonly used in surgery, it
has been found that Chlorine antiseptics and mercury salts have
little effect on phagocytosis in comparison with other germicides.
The activity of the leucocytes from wounds which have recently been
treated with CHLORON may be demonstrated experimentally.”
“In addition to its antiseptic action CHLORON is a strong oxidizing
agent and deodorant and possesses to a marked degree the property
of decomposing toxins. In this connection it is interesting
and pertinent to note that Dean, by the regulated action of
hypochlorous acid, has prepared a nontoxic dysentery vaccine and it
is now a common observation that the free use of CHLORON may reduce
the constitutional symptoms arising from septic processes and that
they reappear on discontinuing the antiseptic treatment.”
Dakin and Dunham Handbook of Antiseptics:
“The ideal surgical antiseptic should effect complete sterilization
within its sphere of action without causing any damage to animal
cells. At the moment such a substance does not appear likely to be
found, but on the other hand it is surprising to see how little
damage may be done to animal tissues by some active antiseptics.
An important method of judging of the injurious action of
antiseptics is to investigate the condition of the leucocytes in
wounds recently treated with the substance under consideration.
In general it appears from experiments _in vitro_ that, with the
strength of antiseptics commonly used in surgery, mercury salts
and hypochlorites have relatively little effect on phagocytosis as
compared with phenol (Parry Morgan). It is a regular phenomenon to
observe activity of the leucocytes obtained from wounds which have
been recently treated with hypochlorites.
Ingenious methods for determining the influence _in vivo_ of
antiseptics on the activities of leucocytes have been worked out by
Col. C. J. Bond.
“In addition to their disinfecting action, the Chlorine antiseptics
are strong oxidizing agents and deodorants and moreover possess in
high degree the property of decomposing toxins. By the regulated
action of hypochlorous acid, Dean has prepared a nontoxic dysentery
vaccine and it is a common observation that the free use of
hypochlorites may reduce the constitutional symptoms arising from
septic processes and that they reappear on discontinuing the
antiseptic treatment.”
Chlorax
Chlorax is said to be “A stable CHLORINE solution for internal use,” in
“Kidney Conditions,” “Diabetes,” “Acute Infections,” “Blood Dicrasias,”
“Lithemias and Rheumatism,” and “Nervous Conditions.” It is claimed to
have the same composition as that of Chloron with the addition of 0.016
per cent. of tincture of opium.
The A. M. A. Chemical Laboratory reported that the free chlorin in
Chlorax was 0.01 gm. per hundred c.c. and the total amount of active
(“available”) chlorin was 0.25 gm. per hundred c.c., or 125 per cent.
of the amount claimed. The laboratory notes that though the chlorin
content of Chloron and Chlorax is claimed to be the same, that of
Chlorax actually is less. This is not surprising when the presence in
Chlorax of reducing substances such as alcohol is borne in mind. The
laboratory concludes that Chlorax is not of reliable composition.
The following is typical of the “case reports” submitted to show the
value of Chlorax:
“In January last I used Chlorax on a case of Diabetes Mellitus and
with excellent results.
“The patient had been suffering for about nine years and when first
brought to my care Toxemia had set in, he was drowsy, irritable
and unable to leave the house. I prescribed Chlorax in teaspoonful
doses four times a day and am pleased to say that in one week he
showed marked improvement. Soon after he was able to leave the
house and attend to his business and after two months’ treatment
resumed a normal diet and habits apparently without injurious
effects.
“I believe that in this case Chlorax undoubtedly prolonged life.”
No mention is made of the dietary or other measures used. The wide
variation in diabetes and its response to proper diet is so well known
that the noncommittal statement concerning the beneficial effects of
Chlorax amounts to no evidence at all in favor of the preparation.
The other “case reports” furnished by the Chlorine Products Company,
Inc., which concern the treatment of gastric ulcers, acute alcoholic
gastritis, tonsillitis, etc., are equally unconvincing. In fact, no
satisfactory evidence for the clinical value of Chlorax has been
presented.
The following from the advertising for Chlorax is unwarranted and
absurd:
“Mercurous chloride (calomel) is perhaps the most widely used
internal antiseptic and alterative and has established itself in
the therapy of constipation, cholera, dysentery, cardiac dropsy,
pleurisy, malignant fever, malaria, syphilis, worms, infectious
diseases, gout and rheumatism; lithium chloride is particularly
efficacious in acute and chronic parenchymatous nephritis and in
various lithemic conditions; while Opium has no rival as an anodyne
and can be used to stabilize and conserve the alkaline reserve of
the body against the acidosing influence of infections.”
Further, on page 14 we find:
“In chills and fever malaria and other blood dicrasias, CHLORAX
is indicated as an internal antiseptic and it exerts a beneficial
effect on the course of these diseases.”
The claims made for Chlorax are exaggerated and misleading.
Number “3”
According to the label, Number “3” is “A STABLE CHLORINE remedy for the
purification of the blood,” with the composition:
“Free Chlorine, 0.35 per cent.; Calcium Chloride, 0.30 per cent.;
Mercurous Chloride, 0.03 per cent.; Lithium Chloride, 0.04 per
cent.; Calcium Hydrate, 0.01 per cent.; Opium, 0.02 per cent.;
Ethyl Alcohol, 0.10 per cent.; water to 100 parts.”
It will be noticed that the composition claimed for Number “3” is
essentially similar to that claimed for Chloron. It differs from
Chloron in that the amounts of some of the constituents are somewhat
greater, and in that, like Chlorax, it contains some tincture of opium.
The A. M. A. Chemical Laboratory reports that the free chlorin in a
specimen of Number “3” was 0.024 gm. in 100 c.c. and the total active
(“available”) chlorin 0.173 gm. per hundred c.c., or about 50 per cent.
of the claimed amount. The examination indicates that Number “3” is of
unreliable composition. The Chlorine Products Company, Inc., submitted
no clinical evidence for Number “3” to which it refers as “our Syphilis
remedy.” It stated that two physicians had used the preparation “with
good results,” and admitted that “the company requires further evidence
before pushing it.”
The Council declared “Chloron,” “Chlorax” and “Number ‘3’” in conflict
with the rules governing admission to New and Nonofficial Remedies. All
are of unreliable composition (conflict with Rule 1). The therapeutic
claims made for the preparations are not substantiated by acceptable
evidence and are unwarranted and misleading. Chloron is inferior as an
antiseptic to the well-known surgical solution of chlorinated soda on
account of its low chlorin content and uncontrolled reaction. There
is no warrant for the claim that Chlorax is useful in the treatment
of “Kidney Conditions,” “Diabetes,” “Acute Infections,” “Blood
Dicrasias,” “Lithemias and Rheumatism,” and “Nervous Conditions,” nor
is there warrant for the claim that “Number ‘3’” is a remedy for the
purification of the blood or a “Syphilis remedy” (conflict with Rule 6).
The names of these pharmaceutical mixtures are not descriptive of their
composition (conflict with Rule 8).
All three preparations are irrational. No evidence has been furnished
that the lithium salt is of value in the mixtures. It is not rational
to combine an active chlorin preparation and a mercury salt in one
mixture, nor is there evidence that the addition of opium to the
preparations proposed for internal use is of value or rational.
Experimentation with Number “3” as a “Syphilis remedy” is to be
severely condemned in that those on whom it is used will in the
meantime be deprived of efficient medication (conflict with Rule
10).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 70_)
ELARSON OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
announcing the omission of Elarson from New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Elarson, now sold by the Winthrop Chemical Company, Inc., was formerly
sold in the United States by the Bayer Co., Inc. It was admitted to New
and Nonofficial Remedies in 1914.
The circular issued by the Winthrop Chemical Co. contains several
statements markedly at variance with the results of an investigation
made, at the request of Fischer, by Joachimoglu (_Arch. f. exper. Path.
u. Pharmakol._ 78:1914). The circular states that Elarson contains
about 13 per cent. arsenic. Joachimoglu found from 10.8 to 11.1 per
cent. to be present. The circular states further:
“The fact that Elarson represents a lipoid-like chemical
combination of arsenic has an important bearing upon its absorption
and utilization in the system ... there is good reason to believe
that when arsenic is administered in a stable, lipoid-like
combination, as in Elarson, it is more readily taken up by the
cells and more completely utilized than when given in the customary
manner.”
“As regards the behavior of Elarson in the system, it has been
shown that its active constituent, chlorarseno-behenol, is almost
completely absorbed in this form, probably as a chlor-behenolate of
sodium or potassium.”
As a matter of fact, Joachimoglu found that very little arsenic was
absorbed when Elarson was given to dogs and rabbits; most of it was
recovered from the feces; only traces were found in the liver and
kidneys and none in the blood and brain. The absence from the latter
organs shows that the lipoid solubility does not obtain in the body. It
is claimed in the circular that Elarson has the advantage over Fowler’s
solution “in that it is free from any irritating action upon the
gastro-intestinal tract”; it is stated that as many as sixty tablets
have been given to dogs daily without any toxic effects. Joachimoglu,
on the other hand, found powdered Elarson to be very irritating to
the gastro-intestinal tract; also that the dog could not stand sixty
tablets at all (_gar nicht vertragen_), such doses causing vomiting,
diarrhea and intestinal hemorrhages; on repeated administration the
symptoms became progressively more severe. Joachimoglu also found that,
compared on the basis of arsenic content, Elarson, given intravenously,
is from ten to twelve times as poisonous as arsenic trioxid. Elarson
is recommended for the class of cases in which Fowler’s solution is
used.
To sum up: None of the special claims made for Elarson--the arsenic
content, ready absorbability, freedom from irritating action on the
gastro-intestinal tract and its alleged better adaptation for continued
administration--have been substantiated; on the contrary, they have
been disproved as well as the theory of its mode of absorption proposed
by Fischer and Klemperer. Furthermore, Joachimoglu found that when it
actually got into the circulation (intravenous injection) in the form
in which Fischer and Klemperer supposed it to be absorbed, it was from
ten to twelve times as toxic as arsenic trioxid.
The Council voted to omit Elarson from New and Nonofficial Remedies
because it is sold under unproved and consequently unwarranted claims
and because it is an unscientific and relatively useless article.
Elarson has not been shown to have advantages over Fowler’s solution;
on the contrary, in some respects at least, it is inferior.--(_From
Reports of Council on Pharmacy and Chemistry, 1919, p. 75._)
IODIPHOS
Report of the Council on Pharmacy and Chemistry
A report which appears below was sent Charles L. Heffner for
consideration. No reply having been received, the Council authorized
its publication.
W. A. Puckner, Secretary.
Iodiphos, marketed by Charles L. Heffner, Brooklyn, N. Y., is declared
to contain ferric citro-iodine, 6 grains; calcium glycerophosphate,
8 grains; sodium glycerophosphate, 8 grains, and hypophosphorous
acid, 2 minims in each fluidounce, and to present “the Metallic and
Non-Metallic elements: Iron, Iodine, Phosphorous, Calcium and Sodium
(each in separate Basic combination).”
According to the label, Iodiphos is “ALTERATIVE, TONIC, NERVINE and
ANTI-TUBERCULAR” and is “For Treatment of BLOOD, NERVES and PULMONARY
ORGANS.” An advertising circular[129] asserts that “Iodiphos exerts its
Physiological action rapidly in hardening of the Arteries, High Blood
Pressure, Anaemia, Glandular Swelling, Neurasthenia, Hypochondria,
Phthisis, Bronchitis, Asthma, Pneumonia and as an Intestinal Antiseptic
and Appetizer,” and declares it to be “Indispensable as a Tonic and
Restorative.”
[129] After publication of the foregoing report had been authorized by
the Council, a letter was received from Charles L. Heffner, advising
that the distribution of the circulars has been discontinued.
In the advertising circular it is averred that in the production of
Iodiphos “Chemistry Again Aids the Modern Physician.” Iodiphos is
another instance when a decadent polypharmacy proposes haphazard
medication and so obstructs the efforts of modern medicine to establish
the use of single drugs to meet definite indications.
Iodiphos is inadmissible to New and Nonofficial Remedies because it
is an irrational mixture of drugs sold with therapeutic claims that
are unwarranted, and under a name which is not descriptive of its
composition.--(_From Reports of Council on Pharmacy and Chemistry,
1919, p. 81._)
MERVENOL AND ARMERVENOL NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the report which appears
below declaring Mervenol and Armervenol, marketed by the Hille
Laboratories, inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Mervenol is stated by the proprietors--The Hille Laboratories,
Chicago--to be a hydrosol (colloidal suspension) of the sulphides of
mercury and copper, containing sufficient sodium chloride to make it
isotonic with blood serum, and “inert proteid” and “carbohydrate” to
stabilize the colloidal suspension: each cubic centimeter is stated to
contain 0.005 gm. mercury, 0.0016 gm. copper, and 0.0016 gm. sulphur.
It is claimed that this preparation is of value in pneumonia,
influenza, and other conditions and diseases requiring increased
leukocytosis.
It is further claimed that the properties and therapeutic effects of
this preparation are as follows: “Practically non-irritant; practically
non-toxic; lower temperature, often crisis like; lower pulse, with
better elimination; greatly accelerated recovery from Influenza;
fewer Pneumonia complications; lower mortality rate in Influenza and
Pneumonia; remarkable Leucocyte stimulation.” Administration by mouth
and by intramuscular and intravenous injection are advocated.
In the recent influenza epidemic, it is reported that therapeutic
results of some value were obtained at the Great Lakes Training
Station and at Fort Sheridan. The reports of certain medical officers
indicate that this preparation seemed to have some effect on the
course of pneumonia and influenza, on the temperature, and on the
leukocyte count. But those conducting the experiments state that it was
“absolutely impossible” to fulfil ideal conditions as to controls and
other observations at the time the experiments were conducted.
So far as the Council knows, no effort has been made to determine the
potent constituent, or constituents, of this preparation; whether the
mercury, the copper, or the protein in the mixture was responsible for
the claimed benefits is an open question.
These reports were given careful consideration, but it was decided
not to accept this preparation because of (1) exaggerated therapeutic
claims, conflicting with Rule 6 (aside from the report of its use
in influenza and pneumonia at the Great Lakes Training Station and
the Post Hospital at Fort Sheridan, which reports are of work done
and observations made under conditions which did not permit careful
controls, no evidence has been presented to the Council supporting the
therapeutic claims) and (2) being an irrational mixture, conflicting
with Rule 10--a mixture containing colloidal mercury, copper and
sulphur with proteins and carbohydrates in addition, it is difficult to
predict the changes which occur in such mixtures on standing.
Samples of Mervenol (two 1-ounce bottles) submitted by the
manufacturer, June 5, 1919, were found when opened, Aug. 18, 1919, to
have undergone decomposition. A very disagreeable odor had developed,
the liquid was turbid, and a large amount of precipitate had formed.
Armervenol is stated by the proprietors--The Hille Laboratories,
Chicago--to be a hydrosol (colloidal suspension) of
“mercury-copper-sulpharsenite” containing sufficient sodium chlorid
to make it isotonic with blood serum and “inert proteid” and
“carbohydrate” to stabilize the solution: each cubic centimeter is
declared to contain 0.0025 gm. arsenic, 0.005 gm. mercury, 0.0016 gm.
copper, and 0.0032 gm. sulphur.
The use of Armervenol as advised by the Hille Laboratories is the same
as that of Mervenol, and in addition its use in syphilis is emphasized.
The criticisms of this mixture are similar in every respect to those
directed against Mervenol--the addition of arsenic introduces still
another factor of uncertainty.
After investigating these claims, it was decided not to accept this
preparation on the ground (1) that the therapeutic claims are unproved
and unwarranted, conflicting with Rule 6, and (2) that the mixture is
an irrational one, conflicting with Rule 10.--(_From Reports of Council
on Pharmacy and Chemistry, 1919, p. 82._)
NORMAL PHENOL SERUM (CANO) AND METHYL-PHENOL SERUM (CANO)
NOT ACCEPTED FOR N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following statement declaring Normal Phenol
Serum (Cano) and Methyl-Phenol Serum (Cano) ineligible to New and
Nonofficial Remedies.
W. A. Puckner, Secretary.
No statement of the composition of these preparations was submitted
to the Council and none appears on the labels of the trade packages.
However, the advertising circular contains statements such as:
“... normal phenol serum--phenol with methyl blue dissolved in
anaphylactic serum ...”
“... a combination of human or horse serum with Phenol and
Methylene-blue, thereby forming a new chemico-biologic product
which he termed Methyl-phenol Serum or, chemically, Chloride of
Phenol Thionin Tetramethylene-Seric.”
“Methyl-phenol Serum is a chemico-biological product in which
Phenol is the chief factor. Each ampule of 10 c.c. contains the
therapeutic equivalent of 0.5 gm. (7.5 grains) of Phenol.”
From the foregoing it appears that both preparations contain phenol and
methylthionine chloride (methylene blue) and that the second does not
contain methyl phenol (cresol) as the name would indicate.
No definite evidence for the value of these preparations is brought
forward and even the manufacturer is constrained to caution, “We assume
no responsibility for the therapeutic action of the serum....” On the
other hand there are a great many statements in the papers of Cano and
his colleagues to which exception must be taken. Of these, from among
many similar, the following statements are to be cited and commented on:
“Accepting that the gonorrheal infection gives systemic toxemia
from absorption of the toxins ...”
It is the general opinion that in the majority of instances there is no
systemic toxemia.
“The technique of intraprostatic injection, while less simple than
that of the intravenous, is by no means so difficult or complicated
as to place it exclusively in the category of the urologist.”
This obviously is an attempt to encourage the general use of these
preparations and to minimize the necessity for careful study and
special skill in their employment. It is most unwise for one to attempt
intraprostatic injections unless he is specially trained in the
technique of this procedure.
“This injection to be performed after the 5th or 6th intravenous
injection of Methyl-phenol Serum....”
Intravenous injections have a place in sane therapy only when the
medicament to be so administered is of known composition and when
evidence is available which gives assurance that definite results shall
follow its use. In the absence of these conditions it is manifestly
unwise and even unexcusable to employ any medicament in this manner,
and its repeated use is reprehensible.
“Intravenous injection of Methyl-phenol Serum alternating with
intravenous injections of mercury should be given every 48 hours
until infection is under control.”
This quotation further emphasizes that the treatment, as advised,
carries with it a certain element of danger.
“Methylene blue prevents the phenol from exerting its usual action
upon the red blood corpuscles, and ensures rapid elimination
through healthy kidneys. It preserves the antiseptic power of
the phenol and prevents the phenol from interfering with the
chemico-biological function of the white and red blood cells. The
serum component favors chemotaxis, it strengthens bodily defense,
it prevents anaphylaxis even in debilitated patients, and it
replaces the resistance which has been impaired by the demands that
have already been made upon it.”
No evidence is submitted to substantiate these claims. It seems strange
that phenol should lose its power and that this should be restored by
the methylene blue.
“It has a refractory chemico-biological action, and exercises no
vicious effect on the red blood corpuscles in the circulation, but,
on the contrary, by its inoffensive presence, it wholly preserves
all of the physiological properties of the blood.”
What “a refractory chemico-biologic action” is, is not clear, but
there is no evidence that this preparation has any action which might
be defined as “refractory chemico-biological,” that its presence is
inoffensive or that it wholly preserves all the physiologic properties
of the blood.
“The treatment of gonorrhea by Cano’s theory ... is firmly
based upon chemico-biological facts and accepted authoritative
theories and bears the same relation to gonorrhea that intravenous
injections of arsenicals bear to syphilis.”
Quite an exaggerated and unwarranted statement. In the same way,
objection is taken to the following quotations:
“Phenol administered intravenously in combination with methylene
blue, to protect the red-blood globule, undergoes no change, and
preserves all of its actual antiseptic effect on the gonococcus and
its toxins as though employed in the test tube.”
“When thus introduced into the human body its elimination is
unique, effective, antiseptic, germicidal, being completely and
exclusively thrown off through the kidneys in a period varying from
one-half to twelve hours without local injury or disturbance to the
general economy.”
“Combinations of phenol are unstable, but they do have the
advantage of mitigating direct action on the cells and globules.
It is also known that ordinary phenol has a _coagulant action_ on
the albumins and an _oxidizing power_ on the tissues, which power,
if permanent, produces gangrene. By virtue of this dual action it
therefore acts as a _modifier_; by its oxidizing power on the germ
it is germicidal, and prevents the growth of the gonococcus; and
by its coagulant power on the toxins it relieves paragonococcal
lesions (mono- and poly-arthritides) and affections of the serous
organs (endo- and pericarditis, meningitis), and some definite
systemic disturbances, the pathology of which is often confused
with that of other infections.”
“Lymphocytosis is often persistent in some individuals in whom
the internal secretions and the processes of assimilation and
disassimilation are deficient; and because of the lack of these the
organic physiological ferments are insufficient for the mechanism
of nutrition and the phenomena of hematopoiesis.”
Until proof is available showing that phenol, administered
intravenously in the quantities employed in Cano’s Normal Phenol Serum
and Cano’s Methyl-Phenol Serum, acts as a germicide and methylthionine
chloride (“methylene blue”) prevents the deleterious effects of phenol
on the red blood corpuscles; that repeated intravenous injections of
phenol and mercury are without danger; that there is no danger of
anaphylaxis; that the physiologic properties of the blood are preserved
by these medicaments; and, finally, that these preparations have an
effect on gonorrhea and its complications, these substances Normal
Phenol Serum (Cano) and Methyl-Phenol (Cano), are inadmissible to New
and Nonofficial Remedies.
The following quotations taken from the circular are admissions that
these preparations are not innocuous:
“That the economy will tolerate to a surprising degree substances
directly introduced through the blood stream is now well known.
By the intravenous injection of 10 c.c. of methyl-phenol serum we
throw into the human body a massive dose of an alien substance.
The immediate effect of this injection is upon the central nervous
system. The recipient usually becomes either pale or suffused, he
has a ringing in his ears, has a sensation of great altitude, and
occasionally has a dryness of the fauces and a metallic or a garlic
taste.”
“In some patients secondary reactions occur in from one to four
hours after injection. The phenomena we have observed in these
secondary reactions are pronounced chill and rigor ...”
There is no doubt that considerable harm may be done by the intravenous
and by the intraprostatic administration of these preparations and
until there is good evidence showing the therapeutic value of the
treatment, the routine use of these preparations, except perhaps at
hospitals in selected and well controlled and carefully guarded cases,
is to be strongly discouraged.
When the foregoing statement was sent to the Mulford Company for
comment, the firm submitted a letter from Dr. Perry Townsend to the
Mulford Company in which he declared that the results obtained with the
Cano preparations had been satisfactory and without untoward results.
In this letter, Dr. Townsend proposed that a series of injections with
these preparations be carried out under the observation of members of
the Council and the supervision of Dr. Cano or himself.
The report of the Council, the letter from the Mulford Company and that
of Dr. Townsend were sent to a number of urologists for their opinion
concerning this whole matter. It was explained that the referee held
that no reason had been presented which would warrant the Council to
depart from its customary procedure, namely, to require that clinical
evidence be submitted in the form of published reports which permit
investigation and verification by independent observers but that,
before making further recommendation to the Council, he desired the
opinion of urologists of recognized standing concerning the report
submitted to the Mulford Company. All replies received approved the
Council’s position.
The following is one of the replies received:
Your letter in regard to Normal Phenol Serum (Cano) and
Methyl-Phenol Serum (Cano) received. I wish to state that I have
read the correspondence between the Council and H. K. Mulford Co.
and in my opinion the referee and the Council are quite correct in
their attitude in the matter. In my opinion I would emphasize the
following:
(1) There is absolutely nothing about the remedies directed
_specifically_ against the gonococcus and no evidence to show that
any action against them is obtained. As we know there are certain
states of normal serum which are highly toxic and any normal
serum from another animal will produce disturbances in man when
injected intravenously--particularly if repeated. The addition of
substances to serum normal or otherwise is apt to and frequently
does render that serum highly toxic! The substances added in the
instances referred to--phenol and methylene blue are not in any
way calculated to lessen the toxicity of serum. The element of
danger existing in the indiscriminate use of serums intravenously
is, in my opinion, increased by the addition of the substances
mentioned, and it would be unwise to encourage the general use of
any such remedies. Furthermore the products are condemned by the
very evidence of the originators and their admissions are quite
sufficient to deter anyone from using the products as they suggest.
As to the intraprostatic injections with the serums it does not
at all meet my views; although the introduction of serums by this
route have been frequently advocated and I have personally carried
this mode out I cannot allow the impression to go out that it
could be done in a routine manner--nor that no ill results could
follow--for I have seen otherwise. Furthermore from theoretical
standpoint serums need not be given in this way.
In consideration of the opinion expressed by the Council’s
consultants the referee recommended that Normal Phenol Serum (Cano)
and Methyl-Phenol Serum (Cano) be declared ineligible for New and
Nonofficial Remedies because of conflict with Rule 6 (unwarranted
therapeutic claims) without considering possible conflicts with other
rules, and that publication of the report be authorized.--(_From
Reports of Council on Pharmacy and Chemistry, 1919, p. 85._)
SOAMIN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Soamin is the name under which the firm of Burroughs Wellcome and
Company sells its brand of sodium arsanilate. The Council directed the
omission of Soamin from New and Nonofficial Remedies and authorized
publication of the report which appears below after the proprietors of
the product had declined to withdraw or suitably revise the unwarranted
therapeutic claims which it made.
W. A. Puckner, Secretary.
The proprietary brand “Soamin” of sodium arsanilate was admitted to
New and Nonofficial Remedies several years ago at a time when the
therapeutic value of arsanilic acid had not been definitely determined.
Experience with this drug has shown that it is far more dangerous
and also has a more limited field of usefulness than was at first
recognized. The proprietors of the Soamin brand have continued to
include in the list of conditions in which it “would seem” to be a
“very effective agent” cerebrospinal meningitis and pellagra; in fact,
meningitis is the first in the list of conditions mentioned, syphilis
the second and pellagra third. In support of their belief in the
efficacy of the remedy in meningitis, three reports, published from
six to nine years ago, are quoted. In one of these it is stated that
two patients “were cured”; in another report, seven of eight patients
in whom the clinical, but not the microscopic, diagnosis of meningitis
had been made were reported as having recovered; in the third report,
fifty-six of ninety cases were reported cured; in this larger series of
cases the author neglects to state the method of administration. The
firm quotes but one paper (which is a very uncritical report) in regard
to pellagra.
It seems to the Council that the evidence of value of sodium arsanilate
in these conditions (which are now treated by more rational methods) is
too slight to justify the emphasis laid on it by the firm, especially
as sodium arsanilate is admittedly a dangerous agent, several cases of
blindness having been reported from its use.
For these reasons it was voted to omit Soamin from New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1919,
p. 89._)
SOME MIXED VACCINES NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
The consideration of the following “mixed” vaccines was requested by
F. I. Lackenbach, San Francisco:
Special Bacterial Vaccine No. 2 (Staph-Strep. Bacterin) containing
killed _Staphylococcus albus_, _Staphylococcus aureus_ and
streptococcus.
Special Bacterial Vaccine No. 3 (Pneumo-Staph-Strep. Bacterin)
containing killed _Staphylococcus albus_, _Staphylococcus aureus_,
streptococcus and pneumococcus.
Special Bacterial Vaccine No. 4 (Pneumo-Staph-Strep-Coli Bacterin)
containing killed _Staphylococcus albus_, _Staphylococcus aureus_,
_Staphylococcus citreus_, _Bacillus coli_, streptococcus and
pneumococcus.
Special Bacterial Vaccine No. 5 (Influenza Combined Bacterin)
containing killed _Staphylococcus albus_, _Staphylococcus aureus_,
_Bacillus Friedländer_, _Bacillus influenzae_, _Micrococcus
catarrhalis_, streptococcus and pneumococcus.
Special Bacterial Vaccine No. 11 (Pneumo-Strep. Bacterin)
containing killed streptococcus and pneumococcus.
Special Bacterial Vaccine No. 15 (Combined Whooping Cough Bacterin)
containing killed _Bacillus pertussis_, _Staphylococcus albus_,
_Staphylococcus aureus_, _Micrococcus catarrhalis_, _Bacillus
influenzae_, streptococcus and pneumococcus.
Special Bacterial Vaccine No. 16 (Mixed Gonococcus Bacterin)
containing killed gonococcus, _Staphylococcus albus_,
_Staphylococcus aureus_, _Bacillus coli_, _diphtheroid bacillus_,
streptococcus and pneumococcus.
Mr. Lackenbach states that these bacterial mixtures were prepared
for him by E. R. Squibb & Sons. Their sale in interstate commerce is
permitted under the license granted to the latter firm by the U. S.
Treasury Department. However, no evidence of any kind was presented
to the Council proving the therapeutic efficacy of the several mixed
vaccines. As a mixture of two or more kinds of organisms is accepted
for New and Nonofficial Remedies only if there is satisfactory evidence
that its therapeutic use is rational, the Council declared the several
vaccine mixtures ineligible for New and Nonofficial Remedies (Rule
10).--(_From Reports of Council on Pharmacy and Chemistry, 1919,
p. 90._)
SOMNOFORM
Report of the Council on Pharmacy and Chemistry
The Council examined the available evidence for Somnoform, sold by
Stratford-Cookson Company, successors to E. de Trey and Sons, and found
the preparation inadmissible to New and Nonofficial Remedies. The
Council authorized publication of the report which appears below.
W. A. Puckner, Secretary.
Somnoform is sold in the United States by Stratford-Cookson Company,
successors to E. de Trey and Sons. According to the label on a package
of Somnoform sent the Council.
“This mixture contains Chloride of Ethyl, 83 per cent.; Chloride of
Methyl, 16 per cent.; Bromide of Ethyl, 1 per cent.”
Although Somnoform has been on the market for a long time, the
published reports present no proof that it is superior to ethyl
chlorid used alone. Moreover, the published reports and statistics do
not necessarily apply to the Somnoform now sold for the reason that
mixtures of varying composition have been sold as Somnoform in the
past. Thus, when Somnoform was considered by the Council in 1909, it
was claimed to be composed of chloride of ethyl, 60 per cent.; chloride
of methyl, 35 per cent., and bromide of ethyl, 5 per cent. Federal
chemists found, however, that it contained no bromide of ethyl (Notice
of Judgment No. 571). It is a question, therefore, whether a given
report applies to a mixture containing 5 per cent. bromide of ethyl, 1
per cent. of this substance, or none at all.
The present advertising booklet for Somnoform does not present
acceptable evidence of the therapeutic value of the preparation.
An ignorance concerning the elementary facts of physiology and
pharmacology is evident in the second sentence: when having stated that
“Somnoform is the result of several years of study and investigation by
Dr. George Rolland, Dean of the Bordeau Dental School,” the pamphlet
continues: “He sought an anesthetic which would enter, dwell in, and
leave the body in the same manner that oxygen does....”
The claim as to the value of the 1 per cent. of ethyl bromide in the
mixture is highly improbable; certainly no evidence in support of the
claimed value of this constituent is available to the referee.
No evidence is submitted which proves the claim of superiority of
Somnoform over similar preparations, asserted in the following:
“The peculiar manner in which the elements are combined is what
makes Somnoform at once so efficient and so safe.”
The Council declared Somnoform inadmissible to New and Nonofficial
Remedies because, in the absence of acceptable evidence showing its
exceptional safety and value, the claims are unwarranted (Rule 6), and
because the name of the mixture is not descriptive of its composition
(Rule 8).--(_From Reports of Council on Pharmacy and Chemistry, 1919,
p. 90._)
TABLETS FORMOTHALATES
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report which
declares Tablets Formothalates (Tailby-Nason Company, Boston, Mass.)
ineligible for New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Tablets Formothalates are sold by Tailby-Nason Company, Boston,
Mass. On the label a formula is given: “Constituents: Acetanilid
2 gr.; phenolphthalein 1/2 gr. In a balanced combination with
Hexamene [a name sometimes applied to hexamethylenamin] and Oil of
Cinnamon. Indications: Influenza, Colds, Grippe, Headache, Neuralgia,
Rheumatism.” The same formula is given in advertisements and in this
advertisement it is claimed that they are “For Influenza and Grip” and
if “given in the acute stage may avert a serious attack” (_Boston M.
& S. J._, Oct. 3, 1918). The dose is given as one to two tablets at
6 p. m. and repeat at bedtimes.
The A. M. A. Chemical Laboratory reported that the tablets weigh an
average of 0.4882 Gm., or 7-1/2 grains; that they _have_ the odor and
taste of cinnamon; and that they contain hexamethylenamin, are neutral
and therefore give up no formaldehyde in the presence of water alone.
The Laboratory further reported that they contain phenolphthalein and
acetanilid. These tablets were directed to be taken internally and
therefore their effect was not intended to be local.
The amount of hexamethylenamin was not determined, but in any case
could not exceed 5 grains per tablet. It is evident that 4 grains
of acetanilid and 10 grains of hexamethylenamin and 1 grain of
phenolphthalein (in two tablets) “if given in the acute stage” of
influenza would not “avert a serious attack,” as claimed in the
advertisements.
The Council declared Tablets Formothalates inadmissible to New and
Nonofficial Remedies.--(_From Reports of Council on Pharmacy and
Chemistry, 1919, p. 92._)
TRIPLE ARSENATES WITH NUCLEIN
Report of the Council on Pharmacy and Chemistry
The Council has declared Triple Arsenates with Nuclein No. 1 and
Triple Arsenates with Nuclein No. 2, tablets marketed by the Abbott
Laboratories, inadmissible to New and Nonofficial Remedies because
unwarranted therapeutic claims (Rule 6) are made for them and because
they present an illogical combination of drugs (Rule 10). The
publication of the following report has been authorized by the Council.
W. A. Puckner, Secretary.
The following claims are made for Triple Arsenates with Nuclein:
“Puts ‘pep’ and strength back into that patient recovering from
Spanish Influenza, pneumonia, typhoid, or surgical operation. An
extremely powerful reconstructive tonic. Try it for that ‘run down’
feeling.”
Triple Arsenates with Nuclein is said to contain “Strychnin Arsenate
gr. 1/128, Quinin Arsenate gr. 1/64, Iron Arsenate gr. 1/64, Nuclein
Solution mins. 4.” A second preparation, of double strength--Triple
Arsenates with Nuclein No. 2--is also advertised. The Council voted not
to accept these preparations for New and Nonofficial Remedies on the
following grounds:
The quantities of quinin, iron and nuclein in the doses represented in
these mixtures are negligible; thus, one tablet of Triple Arsenates
with Nuclein containing 1/64 grain of quinin arsenate contains only
about 1/90 grain of anhydrous quinin; the tablet containing 1/64
grain of iron arsenate contains 1/210 grain of iron; 4 minims of the
nuclein solution (assuming it to be the “Nuclein Solution-Abbott”)
would contain but 2/5 of a grain of nuclein--a substance which even in
large doses is of questionable therapeutic value. The amounts of iron
and nuclein contained in doses of this preparation are insignificant
in comparison with the amounts present in ordinary foods. The only
substances present in even small therapeutic doses are strychnin and
arsenic. The effects of arsenic and strychnin are very different
and there are comparatively few conditions in which they should be
prescribed at the same time. Hence a preparation containing these
two in fixed proportions is illogical.--(_From Reports of Council on
Pharmacy and Chemistry, 1919, p. 92._)
“ANTI-PNEUMOCOCCIC OIL” AND THE USE OF CAMPHOR IN PNEUMONIA
Report of the Council on Pharmacy and Chemistry
The Council has adopted and authorized publication of the report which
appears below. This report declares “Anti-Pneumococcic Oil” (a solution
of camphor in oil sold by Eimer and Amend, New York) ineligible for
New and Nonofficial Remedies because (1) the recommendations for its
use in pneumonia are not warranted by the evidence, (2) the name is
not descriptive of its composition but is therapeutically suggestive,
and (3) the sale of a solution of camphor in oil under a name
nondescriptive of its composition is unscientific and a hindrance to
therapeutic progress.
W. A. Puckner, Secretary.
The Council having decided to consider Anti-Pneumococcic Oil (Eimer
and Amend, New York), the preparation was assigned to the Committee on
Therapeutics for report. The report that follows was made by a member
of this committee:
According to the advertising, Anti-Pneumococcic Oil is a “twenty-five
per cent. solution of camphor in a thin oil” which was “originated” by
August Seibert, M.D. The following directions are given for its use:
“10 c.c. (150 minims) to every 100 pounds of body weight, to be
injected hypodermically every eight to twelve hours in pneumococcic
pneumonia, as soon after the initial chill as possible.”
It is claimed that the prescribed dose one hour before general
anesthesia begins, “safeguards against postoperative pneumonia,” and,
that “animals can so be immunized against later and otherwise fatal
intravenous pneumococcic infection (Boehnke, Institute for Experimental
Therapy, Frankfort).” The advice is given:
“In pneumococcic meningitis, endocarditis and pleuritis, 3% of
salicylic acid should be added to this oil.”
In an article by Seibert, “Camphor and Pneumococci” (_Medical
Record_, April 20, 1912), a reprint of which is used to advertise
Anti-Pneumococcic Oil, previous work (_München, med. Wchnschr._, No.
36, 1909) is mentioned as the starting point for the use of camphor in
pneumonia. In this article, the author reports his first case, that of
a young woman who entered St. Francis’ Hospital on the third day after
the initial chill “with the symptoms of severe toxemia (unconscious,
temperature 105.5 F., pulse 130, and respiration 40) and involvement of
both lower lobes.” “Large doses of camphor,” 12 c.c. of a 20 per cent.
solution, were injected hypodermically “every twelve hours, resulting
in _gradual_ improvement and recovery by the fourth day, without a
crisis.” Seibert reports success in its use in twenty-one cases, but
gives no case histories or protocols. He admits, however, that in
four out of sixteen cases, following the first twenty-one so reported
certain “limitations of this treatment were observed,” and a “sudden
rise of temperature in two patients on the second and third days of
treatment, respectively, proved to be due to pneumococcic nephritis,
promptly subdued by appropriate doses of urotropin, while the camphor
injections were continued and resulting in speedy recovery.” He further
admits that empyema occurs, and states: “This proves that the camphor
brought into the blood cannot prevent the as yet living organisms,
constantly entering the blood current from the affected alveoli, from
colonizing in the renal and pleural tissue.”
He reports, among thirty-seven patients treated in this manner,
one death, that of a man 68 years old, weighing 200 pounds, with a
fatty heart. Heart failure was the real cause of death. Seibert also
reports some very incomplete experimental work; Dr. Hensel, assistant
and pathologist of the German Hospital, found that “1/10,000 part
of camphor added to the usual culture media inhibited the growth
of pneumococci, while the controls all thrived”; Dr. J. C. Welch,
pathologist of the Lying-in Hospital, found that rabbits infected
with lethal doses of pneumococcus cultures intravenously were saved
by large doses of camphorated oil; fragmentary protocols are given.
The assistant pathologist of St. Francis’ Hospital carried on the
experimental work, adding salicylic acid to the camphor. No blood
cultures are reported. The conclusion reached by Dr. Seibert is that
salicylic acid up to 3 per cent., added to the camphorated oil, is
effective in preventing pleural infection. In the article by Dr.
Seibert, there appear most sketchy reports of cases, recovery being
reported without crisis in from three to nine days.
The referee has made a careful search of the literature, with the
following results: Boehnke (_Berl. klin. Wchnschr._ 50:818, 1913),
using white mice, failed to confirm the experiments reported in
Seibert’s paper, unless camphorated oil were given before the
pneumococci, and even then, he felt that the results were too irregular
to be of great significance. When given with anti-pneumococcic serum,
however, he felt that there was some benefit to be seen by the
administration of camphor; his protocols, however, are not detailed.
There is no report of blood cultures, etc.
Another worker, H. Leo (_Deutsch. med. Wchnschr._ 39:690, 1913),
reported that camphor water given intravenously prolonged the lives of
thirty-eight rabbits inoculated with pneumococci. Here again there were
no adequate protocols and very little evidence of careful experimental
work appears.
In the literature of the past ten years, there appear sketchy clinical
articles on the value of huge doses of camphor in pneumonia. Markevitch
(_Russk. Vrach_, June 27, 1914; abstr., The Journal, Dec. 5, 1914,
p. 2081) treated 226 cases of pneumonia with 5 c.c. of camphorated oil
hypodermically four times daily, at the same time giving digitalis
(amount not stated), with a mortality of 6.6 per cent., whereas, in 322
cases untreated, there was a mortality of 13.3 per cent. He reports
133 grave cases; sixty-six received no camphor; 48 per cent. died. Of
sixty-seven treated with camphor, only 22 per cent. died. He reports
temperature falling by lysis when camphor is used, and comments on the
symptomatic improvement following its use. With the great variation in
the clinical course of pneumonia, the above figures, though suggestive,
certainly need further support before the routine use of camphor as
recommended by Seibert can be sanctioned.
Later articles found on the subject refer to it in a very cursory way,
giving no protocols and no cases, and giving the referee the feeling
that the conclusions were very impressionistic.
RÉSUMÉ
After a careful search of the literature, the referee concludes that:
Huge doses of camphor, to 250 grains in twenty-four hours, may be given
to man without serious results. No satisfactory evidence, however,
appears that camphor has a specific germicidal action on pneumococci
(similar to that of ethylhydrocuprein). The clinical evidence, as
found in the literature, is certainly of very little value. It appears
that the sale of a simple solution of camphor in oil under the guise
of “Anti-Pneumococcic Oil” is to be deplored (a 20 per cent. solution
of camphor in cottonseed oil is official in the U. S. Pharmacopeia
as camphor liniment). It is recommended that the preparation be held
inadmissible to New and Nonofficial Remedies because exaggerated
therapeutic claims are advanced for it, and because the name is not
descriptive of the composition, but is, instead, therapeutically
suggestive.--(_From The Journal A. M. A., Jan. 3, 1920._)
DIAL “CIBA”
Report of the Council on Pharmacy and Chemistry
Dial “Ciba” has not been accepted for “New and Nonofficial Remedies”
because, as the report which follows shows, unwarranted claims are
made for the product. It is a definite new chemical compound which
might be made eligible for N. N. R. if misleading therapeutic claims
were eliminated. The Council directed that Dial “Ciba” be included
with Articles Described but Not Accepted, so that physicians might be
informed with regard to its character and properties.
W. A. Puckner, Secretary.
Dial “Ciba” is a hypnotic manufactured by the Society of Chemical
Industry of Basle, Switzerland, and is sold in the United States by
A. Klipstein and Company, Inc., New York. Chemically, Dial “Ciba”
is diallylbarbituric acid and is, therefore, closely related to
diethylbarbituric acid or barbital (“veronal”).
The claims made for Dial “Ciba” are (1), that the “allyl” group in its
molecule makes it more readily decomposed by oxidizing agents than
barbital, which contains the “ethyl” group; (2) that because of this
ease of oxidation, it is more readily decomposed in the body and more
rapidly and completely eliminated, and (3) that because of its alleged
rapid elimination, it is devoid of the after effects of barbital and
other hypnotics.
The Council took up the substance in February, 1918, and referred the
matter to the referee in charge of barbital preparations. The referee
considered unwarranted the claim that Dial “Ciba” did not have the
after-effects of other hypnotics due to its alleged total decomposition
in the body. The American agents, A. Klipstein and Company, were
informed of the referee’s objections. Their attention was also called
to the fact that, notwithstanding the claimed absence of after-effects
in one part of the advertising, other parts of the same advertising
admitted certain post-hypnotic effects of the product. It was
pointed out also that while it was claimed in one of the advertising
circulars that lowering of the blood pressure is never observed after
administration of Dial “Ciba,” yet two of the authors quoted in the
same circular definitely stated that a lowering of the blood pressure
followed even small doses of the drug and these authors warn against
this very danger in certain conditions.
A year later, a circular letter sent out by A. Klipstein and Company
reiterated the claim that the asserted decomposition of Dial “Ciba”
in the body prevents after-effects, the drug being still contrasted
with barbital (“veronal”). In view of the reiteration of this highly
improbable claim, the referee undertook to study the comparative action
of Dial “Ciba” as compared with other hypnotics. It was found that
the actions of Dial “Ciba” are not distinguishable, qualitatively,
from those of barbital, there being no perceptible difference in the
after-effects or in the nature of the side actions. In toxic doses,
both caused profound depression with the temperature falling to
that of the room (or about one degree above), the respiration being
extraordinarily slow and shallow as one would expect with lowering of
the temperature. There were also the same evidences of nausea that
are so frequently seen after toxic doses of the various hypnotics of
this group. In view of these results, the Council declared that it is
unwarranted to claim freedom from after-effects for Dial “Ciba.”
The Council held that the following statement is unwarranted:
“The therapeutic field for Dial ‘Ciba,’ as shown by tests on
rabbits, is just as broad as the field for Diethylbarbituric Acid.”
Tests on rabbits do not and cannot show the breadth of the therapeutic
field for a hypnotic. The Council also declared the following statement
improbable, and contrary to the evidence obtained by the referee:
“In dogs, the increase of dosage beyond the therapeutic dose to the
point of death is decidedly in favor of Dial ‘Ciba,’ which required
a larger dose [than diethylbarbituric acid] to produce death.”
The referee’s experiments on cats show that Dial “Ciba” is several
times as toxic as hydrated chloral, and more than twice as toxic as
diethylbarbituric acid (barbital).
Since the circular to which objection was made in 1918 was still being
sent out in December, 1919, the Council held Dial “Ciba” inadmissible
to N. N. R. and voted that report of its action in the matter be
authorized for publication. The Council further directed that Dial
“Ciba” be included with Articles Described but Not Accepted.--(_From
The Journal A. M. A., Jan. 24, 1920._)
APOTHESINE
Report of the Council on Pharmacy and Chemistry
Apothesine is a synthetic drug for producing local anesthesia, made
by Parke, Davis & Company. In the fall of 1917 the Council wrote to
Parke, Davis & Company offering its aid in establishing the identity,
purity and therapeutic efficiency of this synthetic local anesthetic
with the ultimate object of accepting the product for inclusion in New
and Nonofficial Remedies should the facts warrant such acceptance.
The Council’s letter was never acknowledged. After Apothesine was
put on the market the Council desired to accept it for inclusion in
New and Nonofficial Remedies but, unfortunately, was unable to do so
because some of the claims made for the product were not justified by
acceptable evidence. The manufacturers were notified of the Council’s
desire to admit this product to N. N. R. and the wish was expressed
that the company would either so modify its claims as to make the
product acceptable under the Council’s rules or else would submit
evidence to the Council in proof of the claims made and thus permit
the Council to revise its conclusions. Parke, Davis & Company were,
apparently, either unwilling or unable to submit evidence that would
sustain their claims; neither did they offer to modify the claims
themselves. The product, therefore, is ineligible to inclusion in New
and Nonofficial Remedies; it will, however, be listed in the “Described
But Not Accepted” department of New and Nonofficial Remedies. The
report on Apothesine that follows has been authorized for publication.
W. A. Puckner, Secretary.
Apothesine, “the hydrochlorid of diethyl-amino-propyl-cinnamate,” is
an efficient local anesthetic. It belongs to the procain rather than
to the cocain type, that is, it belongs to that type which, while
effective for injection anesthesia (especially when combined with
epinephrin) is relatively inefficient when applied to mucous membranes.
Apothesine may also be used for spinal anesthesia. Its absolute
toxicity is less than that of cocain (as 20 is to 15, see table below)
but about twice that of procain (as 20 is to 40, see table below). It
is non-irritant, is easily soluble and makes a stable solution so that
it may readily be sterilized.
The Council took exception to certain claims made by Parke, Davis &
Company for their product on the ground that these claims were not
supported by acceptable scientific evidence. One of the claims was
that Apothesine is applicable in any case in which any other local
anesthetic is used. This statement, made in many advertisements,
is distinctly misleading as used. When applied to mucous membranes
Apothesine is far inferior to cocain and to some other local
anesthetics, yet the claim obviously suggests that Apothesine is an
efficient substitute for any local anesthetic.
The manufacturers claimed, too, that Apothesine is as potent as cocain.
The claim would lead the physician to think that Apothesine had the
same anesthetic potency as cocain in solution of equal strength. This
statement, so far as it refers to the drug when applied to mucous
membranes, is not in accord with the facts and is true for injection
anesthesia only when stronger solutions are used. The only support
for the claim of equal efficiency appears to be the experiments with
intracutaneous injections made by H. C. Hamilton[130] in Parke, Davis &
Company’s laboratory. These differed considerably from the results of
Sollmann.[131] A further series of experiments were made by Sollmann
to compare still further the diverse results previously reported
by him and Hamilton. The latest series, while showing considerable
variations in the susceptibility of different skin areas, especially
toward Apothesine, demonstrated in every case that the efficiency of
Apothesine is unmistakably lower than that of cocain, being at best one
half. The series also showed that the potency of Apothesine was never
greater than procain and averaged considerably below it.
[130] The Comparative Values of Some Local Anesthetics by H. C.
Hamilton, Detroit, Mich., from the Research Laboratory of Parke, Davis
& Co., J. Lab. & Clin. M. =4=:60 (Nov.) 1918.
[131] Comparative Efficiency of Local Anesthetics, V, by T. Sollmann,
from the Pharmacological Laboratory of the School of Medicine, Western
Reserve University, J. Pharmacol. & Exper. Therap. =11=:69 (Feb.) 1918.
Another claim made for Apothesine which the Council holds is not
supported by evidence is that of superior safety. This claim is made
on the basis of hypodermic injections in guinea-pigs carried out in
the laboratory of Parke, Davis & Company. Such experiments prove
little because of the fact--well known to laboratory workers--that the
use of rodents in toxicity tests made by injecting a drug into the
subcutaneous tissues does not give a reliable index of the relative
toxicity of such a drug for man. This is due partly to the peculiar
resistance of rodents to poisons and partly to the great importance of
the rate of absorption. The organism destroys most local anesthetics so
rapidly that the rate of absorption is more important than the absolute
dose. The absorption from hypodermic injections into guinea-pigs
differs, of course, from that in clinical accidents, especially where
the drug has been applied to mucous membranes. One cannot, therefore,
reliably estimate the degree of clinical danger on animals.
It has been shown that when toxicity tests of local anesthetics are
made on cats these animals seem to respond to the drugs in a manner
more closely approximating humans and it is a suggestive fact that the
more toxic of local anesthetics, as shown by tests on cats, have been
found the most dangerous in clinical use. The _absolute_ toxicity of
Apothesine has been measured by Eggleston and Hatcher[132] by the
intravenous injection in cats. The fatal doses, in terms of milligrams
per kilogram ranged as follows:
Alypin, Holocain 10
Beta Eucain 12.5
Cocain 15
Apothesine 20
Tropacocain 20-25
Stovain 25-30
Nirvanin 30-35
Procain 40-45
[132] A Further Contribution to the Pharmacology of the Local
Anesthetics by Eggleston and Hatcher, from the Department of
Pharmacology, Cornell University Medical College, New York City, J.
Pharmacol. & Exper. Therap. =13=:433 (Aug.) 1919.
The _absolute_ toxicity of Apothesine is, therefore, only a little
lower than that of cocain, and is twice as great as that of procain.
The _clinical_ dangers cannot be predicted by either method, since
clinical accidents depend, in most instances, on idiosyncrasies, or the
technic of application.--(_From The Journal A. M. A., Jan. 24, 1920._)
EUMICTINE
Report of the Council on Pharmacy and Chemistry
The Council has adopted and authorized publication of the report which
appears below. This report declares “Eumictine” ineligible for New and
Nonofficial Remedies because (1) it conflicts with Rule 10 in that it
is unscientific, (2) it conflicts with Rule 6 in that it is sold under
unwarranted therapeutic claims, (3) it conflicts with Rule 4 against
indirect advertising to the public in that the name “Eumictine” is
blown in the bottle for the obvious purpose of bringing the product
to the attention of the public when it is prescribed in the original
package, and (4) because the name is therapeutically suggestive and not
in any way descriptive of its composition.
W. A. Puckner, Secretary.
Eumictine is a preparation from the laboratory of Maurice Le Prince,
Paris, France, and is marketed in this country by George J. Wallau,
Inc., New York. It is claimed that the product is “a balsamo-antiseptic
preparation composed of Santalol, Salol, and Hexamethylene-Tetramine,
in the form of gluten-coated capsules.” Nowhere in the advertising
are the amounts of the ingredients given. According to the
American agent, however, “each capsule is supposed to contain 20
centigrams of Santalol, 5 centigrams of Salol, 5 centigrams of
Hexamethylene-Tetramine.”
Eumictine is advised “in treating genito-urinary diseases (urethritis,
cystitis, prostatitis, pyelitis, etc.).” It is claimed to be “both an
antiphlogistic modifying agent, a well-tolerated diuretic” which “may
be administered for long periods without ill effects.”
The Council declares Eumictine ineligible for New and Nonofficial
Remedies because it is exploited in conflict with the following rules:
It is unscientific (Rule 10). Eumictine is composed of
hexamethylenamin, salol and sanalol in fixed proportions.
Hexamethylenamin may serve a useful purpose in some forms of infection
of the urinary tract, but neither it nor salol is of any considerable
value in gonorrhea. It is now known that the balsamic preparations,
formerly so widely used, do not have the curative effects in gonorrhea
and associated conditions that used to be ascribed to them. To combine
three substances, none of which has any distinct therapeutic value in
the conditions for which Eumictine is proposed, does not enhance their
value. There is nothing original in the combination used in Eumictine,
or in the manner of dispensing it.
It is sold under unwarranted therapeutic claims (Rule 6). These
claims are made not only for the components of Eumictine but for the
combination itself. Though santalol has certain advantages over the
somewhat variable oil of santal and other balsamic resins, it is not
true that santalol “does not cause congestion of the renal epithelium”
or that it does not “produce exanthema as do copaiba, cubebs, and
the ordinary santal oil.” It is not true that salol is “devoid of
toxicity.” Neither is it correct to say that salol “asepticizes and
disinfects the bladder, the prostate and the urethra.” The claim that
hexamethylenamin “is of value when any acute symptoms or tendency to
inflammation subsist” is not justified. The claim that hexamethylenamin
“renders soluble the uric acid and urates” is also without foundation.
The following paragraph is characteristic of the claims made for
Eumictine:
“Anti-gonorrhoic by its Santalol, diuretic, urolytic and analgetic
by its hexamethylenetetramin (Urotropin) antiseptic and antipyretic
by its Salol, Eumictine represents a real therapeutic advance in
the scientific treatment of diseases of the urinary passages.”
Instead of being “a real therapeutic advance” in the treatment of
diseases of the urinary passages, Eumictine presents one of the
complex combinations that have long retarded the scientific treatment
of these diseases. Eumictine also conflicts with Rules 4 and 8 of the
Council.--(_From The Journal A. M. A. Feb. 21, 1920._)
PLATT’S CHLORIDES
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report on
“Platt’s Chlorides.” It also declares the preparation inadmissible
to New and Nonofficial Remedies because its composition is uncertain
and indefinite and because the claims made for it are exaggerated and
misleading.
W. A. Puckner, Secretary
“Platt’s Chlorides,” marketed by Henry B. Platt, New York, is sold
as a disinfectant and germicide. Only incomplete and contradictory
statements have been made in regard to its composition. Many years
ago (about 1899) the composition of Platt’s Chlorides was given as
“The Chlorids of Zn 40 per cent., Pb 20, Ca 15, Al 15, Mg 5, K 5.” The
statement that the preparation contained 20 per cent. of lead chlorid
is interesting, in view of the fact that lead chlorid is soluble in
water at ordinary temperatures to the extent of less than 1 per cent.
In a booklet, also issued a number of years ago, the following “Formula
of Platt’s Chlorides” was given:
“A saturated solution of Metallic Chlorids combined in the
following proportions:
“Sol. Zinc Chlorid 40 per cent.
“Sol. Aluminum Chlorid 15 per cent.
“Sol. Lead Chlorid 20 per cent.
“Sol. Calcium Chlorid 15 per cent.
“Sol. Magnesium Chlorid 5 per cent.
“Sol. Potassium Chlorid 5 per cent.”
The label on a bottle purchased in 1911, describes Platt’s Chlorides as:
“A Highly Concentrated Solution of the Chlorids of Aluminum,
Calcium, Lead, Zinc, etc.”
The label of a bottle purchased in 1919 reads:
“Contains Inert Material: Water 84.0%. Sodium Chlorid 4.8%. Calcium
Chlorid 0.3%.”
This statement is obviously made to meet the requirements of the
federal Insecticide Act. This law requires either that the identity
and the amounts of potent ingredients in disinfecting preparations be
declared or else that the percentage of the inert ingredients of such
preparations be given. The omission from the label of all statements
with regard to the potent ingredients of the preparation and the
absence of such a statement in recent advertising matter suggests
either that the older statements about its composition were false or
else that the composition has been changed.
Tscheppe published (Pharmaceutische Rundschau =8=:109, 1890) an analysis
of Platt’s Chlorides which has been quoted in other publications as
indicating the composition of the preparation. He reported that he
found each quart of the preparation to contain aluminum sulphate 6
ounces, zinc chlorid 1-1/3 ounces, sodium chlorid 2 ounces, calcium
chlorid 3 ounces.
Some years ago (about 1911) the company made the following statement
relative to the germicidal power (phenol co-efficient) of Platt’s
Chlorides:
“... for some time the carbolic acid co-efficiency of our output
has been from 2.5 to 4.3, the average being about 3; namely about
three times stronger than pure carbolic acid.”
In 1912, the U. S. Public Health and Marine Hospital Service reported
(_Bulletin_ 82, Public Health and Marine Hospital Service, p. 69) that
the phenol coefficient of a sample of Platt’s Chlorides was so low
that it could not be determined and also that the sample was found to
contain some mercuric chlorid. In 1913, the North Dakota Agricultural
Experiment Station reported (_Bulletin_, July, 1913, p. 292), that
Platt’s Chlorides contained principally zinc chlorid, also some
aluminum chlorid, calcium chlorid, and traces of mercuric chlorid. The
phenol coefficient, determined by the Hygienic Laboratory method, was
found to be 0.05.
The preceding suggests that the composition of Platt’s Chlorides had
been changed (without notice to the consumer) and that it had been
fortified by the addition of mercuric chlorid. Years ago part of the
advertising of this product was a testimonial from a health official
which declared that, for disinfection, “bichlorid of mercury is useless
in disinfecting sputum or discharges from the bowels, being rendered
inert by the albumin present” and it lauded Platt’s Chlorides as devoid
of such drawbacks.
RECENT ANALYSES OF PLATT’S CHLORIDES
To determine the present composition of Platt’s Chlorides and to
compare it with that sold formerly, the A. M. A. Chemical Laboratory
has made an analysis of a specimen purchased in 1919 and also of one
purchased in 1911 and since kept unopened in the files of the Council
on Pharmacy and Chemistry. The following table contains the results of
these analyses (all quantities given are Gm. per 100 c.c.):
1911 SPECIMEN 1919 SPECIMEN
Color Colorless Straw Color
Odor None None
Specific Gravity at 25 Cc. 1.1229 1.1313
Total Solids (residue at 100 Cc.) 16.49 18.33
Chlorid (Cl-) 7.60 10.74
Sulphate (SO₄--) 1.11 .16
Aluminum (Al+++) .22 .90
Calcium (Ca++) .19 .13
Zinc (Zn++) 5.11 3.93
Lead (Pb++) .046 Traces
Mercury (Hg++) .. .0086
Sodium (Na+) 1.01 1.39
These quantities transposed to hypothetical combinations would indicate
that Platt’s Chlorides has the following composition:
1911 Specimen 1919 Specimen
Aluminum Sulphate 1.32 .18
Aluminum Chlorid .07 4.29
Calcium Chlorid .54 .37
Zinc Chlorid 10.66 8.19
Lead Chlorid .06 Traces
Mercury Chlorid .. .0116
Sodium Chlorid 2.57 4.81
Hydrogen Chlorid .43 None
In the past, the advertising has suggested, more or less directly,
that, as chlorinated lime (bleaching powder) may be made to give off
chlorin gas which disinfects, so the air in a room may be disinfected
by evaporating Platt’s Chlorides. Thus the label of the 1911 specimen
contains the following:
“FOR STORE ROOMS, Refrigerators, and Closets, keep a sponge
saturated with the pure liquid in a saucer on an upper shelf.”
On the label of the 1919 specimen, the statement reads:
“REFRIGERATORS AND STOREROOMS--As a disinfectant wash regularly
with one part Chlorides to eight of water. As a deodorant, keep in
an open vessel a sponge or cloth saturated with the Chlorides full
strength.”
That the owner of Platt’s Chlorides really believes that the vapors of
the preparation have disinfecting properties is seen from a letter over
the name of Henry B. Platt printed in the New York _Tribune_ in 1916.
This read, in part:
“... by keeping in a dish or saucer on radiators Platt’s Chlorides
diluted one-half, the hot solution will evaporate and purify the
air, thus destroying the grip germ which is the cause of all the
trouble.”
From the analysis of Platt’s Chlorides, it is evident that when the
preparation is evaporated, water vapor only escapes.[133] Whatever
disinfecting or germicidal action the preparation may possess is
exercised only when the solution is brought in direct contact with the
substance to be disinfected.
[133] It is well known that when a solution of mercuric chlorid in
water is evaporated, mercuric chlorid passes off with the water vapors,
but under any condition the amount is but a fraction of the whole. As
in Platt’s Chlorides other metallic chlorids are present, the formation
of complex mercuric compounds which is bound to have occurred, should
retard or prevent the volatilization of mercuric chlorid. That this
actually occurs was confirmed by the following experiment: When 1 gm.
mercuric chlorid was dissolved in 1 liter of water and the solution
distilled, the distillate contained a very small amount of mercury.
Then the experiment was repeated after adding sodium chlorid to the
solution to simulate the conditions in Platt’s Chlorides. In this case
no mercury was found in the distillate. Even were all the mercury in a
bottle of Platt’s Chlorides volatilized in a room 10 by 12 by 9 feet,
this would be equivalent to only about 1/500 grain mercuric chlorid per
cubic foot.
The aluminum and zinc salts present may be useful as deodorants but
they are not effective as germicides. The presence of mercuric chlorid
in a concentration of 1 to 10,000 is hardly to be considered as
materially increasing the efficiency. The directions recommend the use
of a mixture of 1 part of Platt’s Chlorides to 10 parts of water for
rinsing the hands, and a mixture of 1 part to 4 parts of water for the
disinfection of discharges. It is further stated that 1 quart makes 2
gallons sufficiently strong for general use. It is evident that such
dilutions decrease considerably the feeble germicidal action of the
original fluid.--(_From The Journal A. M. A., March 27, 1920._)
ANTI-TUBERCULOUS LYMPH COMPOUND (SWEENY) AND ANTI-SYPHILITIC
COMPOUND (SWEENY)
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the reports which appear
below, declaring Anti-Tuberculous Lymph Compound (Sweeny) and
Anti-Syphilitic Compound (Sweeny) ineligible for New and Nonofficial
Remedies.
W. A. Puckner, Secretary.
Anti-Tuberculous Lymph Compound (Sweeny)
“Anti-Tuberculous Lymph Compound (Sweeny)” is put out by the National
Laboratories of Pittsburgh, Dr. Gilliford B. Sweeny, “Medical
Director.” Sweeny has claimed at different times that he became
interested in the subject of von Behring’s efforts to immunize cattle
to tuberculosis at a time when he was an assistant in von Behring’s
laboratory. He claims to have conceived the idea while there of
transferring bovine immunity to tuberculosis to the human subject and
later to have evolved his “treatment” at the Pasteur Institute in Paris.
Just how Anti-Tuberculous Lymph Compound is made today is not
stated--at least so far as one is able to learn from recent
advertising. Some years ago Sweeny declared that his “Anti-Tubercular
Lymph” (as it was then called) was derived from a bullock which had
been immunized to tuberculosis. Then:
“The immunized animal having been slaughtered, the contents of the
lymph reservoirs are carefully collected and an aqueous extract is
made from the grey cerebral substance, spinal cord and the lymph
glands. It is then filtered under high pressure and de-albuminized
by succussion. To this, the lymph, together with a definite
proportion (50 per cent.), of the naturally phosphorized brain fats
is added, with a small amount of chloride of gold (about 1-60 gr.
to the dose), the latter as a preservative.”
It is a fair assumption that however the preparation may have been
made originally, it is not now made in such a manner as to bring it
under the federal laws governing the preparation of serums and similar
preparations. The claims made for Anti-Tuberculous Lymph Compound are
of the usual uncritical and unscientific type. Mainly, of course,
they are of the testimonial class. The physician is told that the
preparation has been carefully tested by men whose judgment is worthy
of consideration; that the verdict has been altogether favorable to the
“Compound.” Thus:
“... the remedy was submitted to a selected body of skilled
physicians, recognized for their skill and care in making
therapeutic observations. These men represented widely varying
conditions, climatic and otherwise. Those who said ten years ago
that Anti-Tuberculous Lymph Compound has a specific immunizing
influence upon the tuberculosis patient, find the same to be true
today.”
Careful reading of the matter just quoted will reveal its ambiguity
and inherent lack of frankness. The inference conveyed is that the
“selected body of skilled physicians” have unqualifiedly endorsed
Anti-Tuberculous Lymph Compound (Sweeny)--but it does not say so!
It is the history of all such preparations, introduced to the medical
profession with the usual blare of trumpets, that a certain number of
favorable testimonials can be obtained. It is also the history of such
products that one has but to wait a few years and the physicians who
had written most enthusiastically regarding the preparation--in the
first flush of their optimism following its use and the perusal of the
manufacturers’ literature--will acknowledge that they were mistaken
in their original estimate and are no longer using the agent. In
this connection an investigation of some of the old testimonials for
Anti-Tuberculous Lymph Compound by the Propaganda department of The
Journal is instructive.
In a somewhat elaborate booklet published in 1907 by Sweeny, an Indiana
physician was said to have reported favorable results following the
administration of the “lymph.” A letter written to this physician in
October, 1919, asking for his present opinion on the product brought
this reply, in part:
“... it being twelve years since using the serum and no reference
or repeated orders since should surely suffice as evidence of my
lack of faith in the serum....”
An Illinois physician was reported in the same booklet to have
described a case of a young man with an active tuberculosis, who was
given injections of the “lymph” in February, 1907. The patient, it was
claimed, showed immediate improvement and the Sweeny booklet (published
in August, 1907) stated that “improvement in this case continued and
terminated in complete recovery.” A letter written to the physician in
October, 1919, brought out the fact that the young man in question,
after receiving “Anti-Tuberculous Lymph Compound” and _other treatment_
was removed “on a stretcher” “to New Mexico, where he remained for
three or four years” and recovered. The doctor adds:
“I do not think that the Anti-Tuberculous Lymph had anything to
do with the man’s recovery, although I realize the difficulty of
definitely analyzing just what did effect the cure. I did since
that time use that preparation in several other cases without
beneficial results so that I gave it up a good many years ago
adding it to that large heap of pharmaceutical material ‘weighed
and found wanting.’”
A physician in Texas also reported in the 1907 booklet as having had
very satisfactory results with the Anti-Tuberculous Lymph Compound in
one case of pulmonary tuberculosis was written to in October, 1919. He
replied:
“I will state that subsequent use of this compound did not bear out
the apparent good results from its use in the first case or two.”
In a “Bulletin” issued by the Sweeny concern in 1912, a Pennsylvania
physician was quoted as having treated three cases with Anti-Tuberculin
Lymph Compound with resultant cures. This physician was written to in
October, 1919, and he replied:
“I have no knowledge of the use of my name by any Pittsburgh
concern and know nothing of a lymph of the name of Sweeny; neither
do I recollect ever curing three cases of tuberculosis with any
lymph.”
The same “Bulletin” quoted the alleged statement by a Delaware
physician to the effect that he believed Anti-Tuberculous Lymph
Compound to be the most successful treatment of tuberculosis extant.
This in 1912. To an inquiry sent in October, 1919, this physician
briefly replied:
“Am not using it now.”
The result of the Propaganda department’s questionnaire was what might
have been expected. Every physician who answered the inquiry regarding
his previous and present opinions of Anti-Tuberculous Lymph Compound
(Sweeny) declared, in effect, that he had long since ceased to have
faith in its value or efficacy.
According to claims made in Sweeny literature, “Anti-Tuberculous Lymph
Compound exercises its immunizing power through a specific action upon
the blood cells.” The statement that “it destroys the tuberculosis
germ when this is present in the system of the patient” is untrue.
The facts are, no serum or lymph has thus far been proved to have
any value in the treatment of tuberculosis even when fortified by “a
small proportion of chloride of gold and soda” as one circular tells
us the “lymph” is. In spite of research by competent investigators, we
are still without any aid in the form of a serum in the treatment of
tuberculosis.
Anti-Tuberculous Lymph Compound (Sweeny) is one of those preparations
that need no elaborate laboratory tests, nor even exact therapeutic
research, to convince any clear-thinking person that it is patently and
obviously worthless. One would hesitate before asking any reputable
clinician to test a preparation of this sort. It is a constant source
of surprise that some physicians allow themselves to be persuaded by
advertising literature that is obviously uncritical and unscientific,
to use preparations which have no more reasonable foundation than this
one.
The Council declares Anti-Tuberculous Lymph Compound (Sweeny) not
acceptable for New and Nonofficial Remedies.
Anti-Syphilitic Compound (Sweeny)
This preparation also is made by or under the direction of the same
Dr. Gilliford B. Sweeny whose researches (?) led to the production and
evolution of the Anti-Tuberculous Lymph Compound (Sweeny). According to
the data at hand, this preparation is made by suspending benzoate of
mercury in lymph from the bullock. Case reports are given of alleged
cures of syphilis after two months of treatment; indeed, the circular
exploiting the agent makes the statement that it is seldom necessary
to continue the treatment beyond two months, which, if one chose to be
credulous, would indicate extraordinary power for the mercury.
Mercury of course has a proper place in the treatment of syphilis,
but that any physician could be induced to place his trust in this
preparation is almost unthinkable though testimonials--which the
“National Laboratories” claim to have received from physicians--are
published. They all stamp the writers as not only gullible but also
incompetent. The tenor of the claims is on a par with those made for
the Anti-Tuberculous Lymph Compound; they do not justify the time
required for detailed consideration.
The Council declares Anti-Syphilitic Lymph Compound (Sweeny) not
acceptable for N. N. R.--(_From The Journal A. M. A., April 3, 1920._)
SYRUP LEPTINOL (FORMERLY SYRUP BALSAMEA)
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
on “Syrup Leptinol” (formerly “Syrup Balsamea”). The product is
inadmissible to “New and Nonofficial Remedies,” first, because the
manufacturers fail to give the profession information regarding either
the amount of the potent ingredient or the method of determining
its identity and uniformity; second, because of the unwarranted
recommendation for its use in such infectious diseases as pneumonia and
epidemic influenza and for lack of satisfactory supporting evidence of
its alleged therapeutic efficacy in other diseases and, third, because
the recommendations for its use appearing on and in the trade package
constitute an indirect advertisement to the public.
W. A. Puckner, Secretary.
Syrup Leptinol is sold by the Balsamea Co. of San Francisco. It was
first introduced as Syrup Balsamea. In recent advertising, Syrup
Leptinol is also referred to simply as “Leptinol.”
According to the statements of the Balsamea Co., Syrup Leptinol is
prepared from the root of a species of Leptotaenia (a plant belonging
to the parsnip family) which grows in Nevada and which has heretofore
not been used in medicine. The manufacturer states that the botanists
who have been consulted have been unable to agree on the botanical
classification of the plant. The dried root of this unclassified
species of Leptotaenia is extracted with alcohol and from the extract
so obtained the syrup is made, but no information has been furnished
to show how the alcohol-soluble material is incorporated in the syrup.
Further, the manufacturer has not announced tests whereby the identity
and uniformity of the finished preparation may be determined.
A booklet contains the following:
“The species of Leptotaenia from which LEPTINOL is produced was
first used in medicine by Dr. E. T. Krebs, who, after thorough
laboratory investigation and clinical application over a period
of several months, which resulted in the perfecting of LEPTINOL,
prescribed the preparation for Influenza during the epidemic of
that disease in 1918 with remarkably good results. Since this first
use, LEPTINOL has been exhaustively tested by clinicians in private
practice and in hospitals in the treatment of Pneumonia, Influenza
Bronchitis, etc., and has been universally endorsed.”
In a circular letter it is asserted that the use of “Leptinol” during
the “influenza epidemic” of 1918-1919 “demonstrated its almost specific
action in respiratory affections”; that “during this epidemic it proved
to be five times as efficacious as any other treatment in pneumonia
...”; and that “it is now as firmly fixed in the mind of many doctors
for respiratory diseases as quinine is for malaria and the salicylates
for rheumatism.”
In the booklet it is further stated that the therapeutic action of
the preparation is primarily that of a “stimulating expectorant” and
secondarily as a “sedative expectorant”; that “its antiseptic action
in the respiratory tract is prompt”; that it “is an effectual cardiac
tonic where the tone of the heart muscle is impaired by fever”; that
“in acute pulmonary conditions it effectively improves the respiratory
action and allays cerebral irritation due to fever and toxins”; that
it acts “as a vital stimulant and nerve sedative”; that “it stimulates
the excretion of acid by the skin and in fever it has a strongly
diaphoretic and antipyretic action without depressing the circulation
or the central nervous system”; that it is “mildly diuretic” and
“slightly augments the biliary flow” and that “it increases the gastric
and intestinal secretions and allays intestinal fermentation.”
No evidence has been presented to the Council which shows that Syrup
Leptinol has the actions ascribed to it. The reports of clinical trial
are little more than chance observations and lack all control. This
applies also to the following, stated to be a quotation from the report
of the Tonopah Mines Hospital Association:
“In the spring of 1919 a recurrence of the Influenza epidemic of
the previous winter was experienced. During the first period of
this second epidemic, prior to April 15th, there were treated one
hundred sixteen cases of Influenza, fourteen of which developed
Influenzal Pneumonia, with six deaths. The Pneumonia was of the
very virulent type which prevails in this high altitude.... After
April 15th, when the clinical use of Leptinol was inaugurated,
three hundred and sixty-eight cases of Influenza were treated
and not a single case developed Pneumonia. Twenty-two cases of
Influenzal Pneumonia were received and treated with LEPTINOL, with
a consequent one hundred per cent. recovery....
“In the cases where LEPTINOL was used the treatment was the same
as had been previously followed, as to diet, fresh air, etc., but
the medication was confined to LEPTINOL. Syrup LEPTINOL was started
immediately in one-dram doses at one-hour intervals, in cases with
high temperatures, and this was continued until temperature and
pulse subsided. It was then used in one-dram doses at three-hour
intervals as recovery progressed. On admission to the hospital,
calomel in 1/4 grain doses, was given at fifteen minute intervals
for eight doses. The last calomel was followed in six hours by 1/2
ounce Magnesium Sulphate in saturated solution. The second day 1/10
grain of calomel was given at one-hour intervals for ten doses....”
Medical journals are replete with reports of remarkable results
obtained with the most varied forms of treatment instituted at the time
that the “influenza epidemic” had been reached. In these cases it is
more than probable that the lessened virulence of the causative factor
of the disease, the gradually established resistance of those stricken
with it in the latter period and the improved management resulting
from experience deserve the credit for the successful outcome of the
treatment, rather than the particular form of medication employed.
The report of the Tonopah Mines Hospital Association directly
implies that Syrup Leptinol prevents the development of pneumonia
in practically all cases of influenza in which it would develop and
that it entirely abolishes the mortality of that disease. However,
it is well known that innumerable remedies have been recommended as
specifics in the treatment of pneumonia on the basis of the treatment
of a limited number of cases which recovered, and that eventually these
asserted specifics have been discarded as of little value. In the
present instance, the recovery of twenty-two cases in succession afford
_prima facie_ evidence that those cases were not the virulent type of
pneumonia in which the death rate is very high under any methods of
treatment. While no effort appears to have been made to determine the
nature of the infecting organism, the records show fairly conclusively
that they belonged to those causing the milder type of pneumonia.
The Council finds Syrup Leptinol (formerly Syrup Balsamea) inadmissible
to New and Nonofficial Remedies because: (1) the information in regard
to composition does not state the amount of potent ingredient, nor
permit the determination of its identity and uniformity; (2) the
recommendation for its use in such infectious diseases as pneumonia
and epidemic influenza is unwarranted and its claimed therapeutic
efficacy in other diseases is without satisfactory supporting evidence;
and (3) the recommendations for its use which appear on the label and
the circular wrapped with the trade package constitute an indirect
advertisement to the public.
The Council accepts the explanation of the manufacturer that he has
been unable to obtain a satisfactory classification of the plant from
which Syrup Leptinol is made. It would be undesirable to exclude
from therapeutic use a valuable drug simply because its botanical
character has not been determined or because an exhaustive chemical
examination had so far not been made. However, in the absence of such
information the manufacturer should give full information with regard
to the preparation or standardization of his remedy and the therapeutic
claims made for it should be accompanied by indisputable, thoroughly
controlled clinical evidence. In the case of Syrup Leptinol, there is
no satisfactory evidence available showing that the preparation has
any value in the treatment of epidemic influenza, pneumonia, whooping
cough, etc. While it is probable that a balsamic syrup, such as Syrup
Leptinol, has palliative properties in coughs, such action does not at
all justify the claim that it is useful in the contagious diseases for
which it is proposed. The Council cannot recognize a syrup presenting
an unknown plant in uncertain proportions which is recommended in a
variety of dangerous contagious diseases in which it ultimately may be
harmful, even though in early stages of these diseases it may serve to
allay some of the milder symptoms.
Concerning the composition of the plant from which Syrup Leptinol is
prepared, the Balsamea Company states that it contains “Alkaloids,
acids, glucosides, volatile and fixed oils, gums and resins.” This
information is valueless, since no information is given concerning the
character, amounts or pharmacologic action of the ingredients. Further,
it is unreliable as far as the presence of alkaloids is concerned since
the A. M. A. Chemical Laboratory has been unable to find any alkaloids
in the specimen of the crude drug furnished by the manufacturers.
In accordance with its regular procedure, the Council submitted the
preceding statement to the manufacturer.
In reply the Balsamea Company stated that it is more than ever of the
belief that Syrup Leptinol is deserving of recognition by the Council,
basing this opinion on further clinical experience with it in the
treatment of influenza.
The manufacturer stated that the use of the words “Leptinol” and “Syrup
Leptinol” interchangeably was due to an oversight and promised to limit
the use of the word “Leptinol” to an alcoholic extract of the plant.
Concerning the method of preparation of this alcoholic extract and the
amount used in the preparation of Syrup Leptinol the Balsamea Company
replied as follows:
“The alcoholic extract of the Leptotaenia, which we have termed
‘Leptinol’ is a preparation of definite and uniform strength, as
determined by two methods: (a) the gravity test using the U. S.
Hydrometer Scale for spirits, by which Leptinol registers 52
degrees at 60 degrees F., and (b) by gentle evaporation of the
alcohol content and the measuring of the active constituents, which
measures twenty-five per cent. by weight.
“The alcoholic extract ‘Leptinol’ is glycerinated in a machine,
using one part of the alcoholic concentration to four parts
of glycerin. This is then added to eleven parts of a heavy
syrup, containing 7-1/2 pounds of sugar to the gallon of syrup,
and thoroughly mixed in an agitating machine. Leptinol is the
sole active ingredient of Syrup Leptinol. Syrup Leptinol is a
preparation of uniform strength. It is far more uniform in strength
than most of the syrups of the U. S. P. made from fluid extracts
which are made from crude drugs which are not uniform in strength.”
This claim cannot be allowed as meeting the conflict with Rule 1. It
is well known that plants vary in their composition at different times
of the year; under different conditions of cultivation and growth;
and under other conditions; hence the claim that alcoholic extracts
of equal specific gravity insure uniformity of composition in active
principles must be considered entirely illogical, especially since the
exact nature of the active principles, if any be present, is unknown.
If these are known their nature should be stated and tests for their
identity be given. If they are unknown it is manifestly misleading to
state that the preparation is of uniform strength.
It is evident that the Council cannot approve of the use of a
preparation of unknown composition without satisfactory evidence of
its value, especially when it is recommended in a variety of serious
infectious diseases such as influenza and pneumonia. The mere fact
that a small number of patients who have received the drug recover
is no evidence of its curative value, and until carefully controlled
clinical tests of the preparation are made, it is not entitled to the
consideration of physicians.--(_From The Journal A. M. A., June 5,
1920._)
FORMITOL TABLETS, II
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following supplementary
report on Formitol Tablets.
W. A. Puckner, Secretary.
In the Council report (The Journal A. M. A., Oct. 4, 1919, p. 1077) on
the ineffectiveness of lozenges claimed either to contain formaldehyd
or to liberate formaldehyd in the mouth, the composition of Formitol
Tablets of the E. L. Patch Co. was briefly discussed in the following
terms:
“The A. M. A. Chemical Laboratory reported that Formitol Tablets
contained formaldehyd (or paraformaldehyd), an ammonium compound,
and some hexamethylenamin. It is probable that the formaldehyd
(or paraformaldehyd) was produced by the decomposition of
hexamethylenamin originally present in the tablets but decomposed by
long contact with the acid.”
At the time this report was published, the label and the advertising
matter contained but vague and indefinite statements with regard to
the composition of Formitol Tablets. In the October, 1919, issue of
_Patchwork_, the house organ of the E. L. Patch Co., it was denied that
these tablets contain hexamethylenamin since none had ever been used in
their manufacture. It was also claimed that the company had a “printed
sheet giving the formula of these tablets.”
The Council advised the E. L. Patch Co. that it desires to publish only
facts about the products which it examines and that if the report on
Formitol Tablets was inaccurate in any way the Council would want to
correct any error it might have unintentionally made. As the Formitol
advertising in the files of the Council contained no information as to
the composition of the tablets, the firm was also requested to send the
printed sheet giving the “formula.”
When this printed “formula” came it was found to be a sheet used by
the E. L. Patch Co. for the purpose of giving its salesmen information
regarding Formitol tablets, to be passed on to the physician. This
printed sheet conveyed the information that Formitol Tablets contain
ammonium chlorid, benzoic acid, citric acid, guaiac, hyoscyamus,
menthol, paraformaldehyd and tannic acid, but it gave no information in
regard to the amount of any of the ingredients except that it declared
that each tablet represents the equivalent of 10 minims of a 1 per
cent. formaldehyd solution.
Because of the nonquantitative, and, therefore meaningless printed
“formula” and because, also, of its complexity, it was thought
desirable to make a more complete analysis of Formitol Tablets.
Experience has shown that frequently the real formula of a thing is
quite different from the alleged formula published by the manufacturer.
The details of the laboratory’s later analysis will appear in the
Annual Reports of the Chemical Laboratory or may be had on request.
The result of the laboratory’s additional experimental work, especially
when taken in connection with investigations made elsewhere on
the interaction of formaldehyd and ammonium chlorid justifies the
conclusion that Formitol Tablets do contain some hexamethylenamin,
even though the amount may be very small. As the E. L. Patch Co.
declare that no hexamethylenamin is put into Formitol Tablets the
conclusion drawn in the Council’s original report to the effect
that the formaldehyd probably was formed by the decomposition of
hexamethylenamin was evidently an error. The hexamethylenamin present
is doubtless produced by the action of the paraformaldehyd on the
ammonium chlorid present.
The analysis also showed that more than 78 per cent. of the weight
of Formitol Tablets was made up of sugars and about 16.5 per cent.
was starch and other material, some of which was talcum or similar
material. This means that about 94 per cent. of the total weight of
the tablets is sugar and starch, neither of which is mentioned in the
printed “formula.” The significance of this is apparent when it is
considered that there are eight ingredients listed in the “formula” for
which therapeutic effects are claimed. Since a tablet weighs about 13.5
grains, the combined weight of all the claimed active ingredients is
less than 1 grain per tablet!
The amount of ammonium chlorid found, as indicated by the total
nitrogen, was not more than 1.0 per cent. or about 1/8 grain per
tablet. The amount of benzoic acid found was 0.34 per cent. or 1/25
grain per tablet. Yet these two drugs are said to exert their peculiar
expectorant action. (The U. S. P. lozenge of ammonium chlorid contains
1-1/2 grains ammonium chlorid or twelve times the amount of this drug
in a Formitol Tablet.)
The tannic acid contained in the tablets could not be determined with
accuracy but it was much less than 1 per cent. (or 1/8 grain per
tablet) yet it is said to add valuable astringent qualities to Formitol
Tablets! (The U. S. P. lozenge of tannic acid contains 1 grain of
tannic acid.)
The quantity of guaiac (as resin) is but a fraction of 1 per cent.
Yet it is said to impart to Formitol Tablets “stimulant resolvent”
properties and it is intimated that there is sufficient to be of value
in “cases of abscess of the throat and inflammation of the tissues.”
The total acidity indicates the presence of about 2 per cent. of
citric acid or 1/4 grain per tablet. Yet this amount is said to be
“antiseptic” and “aids in the general results.”
While the presence of the drug hyoscyamus (henbane) was not positively
identified by microscopic examination, alkaloids were present.
The manufacturers claim that the tablets contain menthol yet only
a suggestion of menthol could be obtained from the odor. However,
the odor of methyl salicylate--a constituent _not_ declared in the
“formula”--predominated throughout the operations of analysis.
Formitol Tablets furnish a good illustration of some well established
but often ignored truths:
1. “Formulas” that are nonquantitative are valueless or worse than
valueless.
2. The fact that a manufacturer puts certain drugs in a mixture, is no
proof that these drugs are there when the mixture reaches the patient.
The physician must be assured that they are there when he prescribes
them.
3. Complex mixtures should be avoided. It is absurd to expect, as
is claimed in the case of Formitol Tablets, anodyne, antiseptic,
astringent, expectorant, and resolvent action all at the same
time.--(_From The Journal A. M. A., June 19, 1920._)
SUKRO-SERUM AND APHLEGMATOL
Report of the Council on Pharmacy and Chemistry
Two years ago, American newspapers contained accounts of an alleged
cure for pulmonary tuberculosis “discovered” by Prof. Domenico Lo
Monaco of Rome, Italy. At that time no reference to the “cure” could
be found in medical journals which had come from Italy and other
European countries (_The Journal A. M. A._, July 13, 1918, p. 142).
Later, reports were published of experiments carried out in Italy,
according to which the intramuscular injection of solutions of sugar
(saccharose--cane sugar) diminished pulmonary secretion and was of
considerable value in the treatment of tuberculosis (_The Journal
A. M. A._, Sept. 28, 1918, p. 1083). On the whole the reports of the
trial of what has been called the Italian Sugar Cure for Consumption
have been unfavorable. At a meeting in Paris in October, 1918, Drs.
Louis Rénon and Mignot reported that they had found that the disease
in guinea-pigs was not modified by the treatment and with humans the
results were also negative (Paris Letter, _The Journal A. M. A._, Nov.
23, 1918, p. 1760).
In view of the exploitation of this treatment in the United States
by the Anglo-French Drug Co., which offers “Sukro-Serum,” and by G.
Giambalvo & Co., which sells “Aphlegmatol,” and because of inquiries
received, the Council has authorized publication of the statement which
follows.
W. A. Puckner, Secretary.
A circular issued by the Anglo-French Drug Co., describes “Sukro-Serum”
as a “Sterilized Solution of lacto-gluco-saccharose.” By reading the
circular to the end, however, one learns that “Sukro-Serum” is not
a “serum” in the ordinary sense but apparently it is a solution of
ordinary sugar (sucrose). “Sukro-Serum is a sterilized, specially
prepared solution of Saccharose.”
Sukro-Serum has been advertised (_N. Y. Med. Jour._, Sept. 6, 1919)
as an “INTRAMUSCULAR INJECTION FOR TUBERCULOSIS” “... ready for use
in cases of Pulmonary and general Tuberculosis” with the assertion
that “It is quite certain that in the near future Sukro-Serum will be
largely used and its value fully recognized.” The circular received
from the Anglo-French Drug Co. contains quotations from an article by
Professor Lo Monaco in the _British Medical Journal_ (Aug. 24, 1918)
setting forth the merits of intramuscular injections of sucrose in
tuberculosis. It is recommended that “Néocaine-Surrénine” (which the
Anglo-French Drug Co. supplies) be used for the control of pain when
Sukro-Serum is injected.
The circular enclosed with a package of “Aphlegmatol,” purchased from
G. Giambalvo & Co., contained the following with reference to the
composition of this preparation:
“A solution of Hydrats of Carbon After the formula of Prof. D. Lo
Monaco, Director of the Institut of Physiological Chemistry of the
University of Rome. Contents: _Sucrose (C₁₂H₂₂O₁₁) Glucose and
Galactose (C₆H₁₂O₆)_.”
The package contained ampules of thin, fragile, brown colored glass,
containing approximately 2-1/2 c.c. of light, clear, amber colored,
thick, sticky fluid, having a distinct caramel odor. Reaction
_p_↓{H} = 5.0. A reducing substance (probably glucose) amounting to 7.4
per cent. was found by using Benedict’s method for estimating glucose
quantitatively; after hydrolysis with hydrochloric acid, 55.5 per
cent. glucose was found. There was no reaction for albumin. No attempt
was made to identify the sugars, as it seemed probable that in the
preparation caramel had been produced.
The circular which accompanied the package of Aphlegmatol contained the
following information (spelling and composition as in original) about
its use and effects:
To be emploied where a large bronchial secretion is present in the
respiratory branches disease. The secretion will diminish and, in
non complicated cases, it will completely disappear.
Fever, cough, hemottisis, night perspiration, vomiting and
difficulty of breathing are, in the meantime, diminuished.
Aphlegmatol acts also as a riconstituent, being itself a nurrishing
composition, improves the digestive function of the body and
increases the arterial pressure.
5 c.c. (2 Phials) of Aphlegmatol per day must be injected
intramuscularly in the Gluteus.
If the patient wishes two injections may be made, one at the right
immediately followed by a second one at the left.
The cure must not be interrupted untill sometime after
expectoration has disappeared, which result may be obtained only
after fifty or sixty days, in the meantime the patient must be
controlled by his home physician, especialy when thermal elevation
of the body takes place.
Improvement will be manifested on or about the tenth day of the
first injection.
In the advertising circular, which is apparently intended for general
distribution, much the same information is given as in the sheet
enclosed with the ampules, except that in the directions we find:
“If the injections are painful--especially in cases where patients
are very emaciated--physicians are advised to inject together with
_Aphlegmatol_, as an anesthetic, a vial with 1 c.c. solution of Stovain
at 3%.” The advertising for Aphlegmatol contains many misspelled words
and appears to be the work of those ignorant of the English language.
Tuberculosis is a widespread disease and a majority of the uninformed
are only too willing and ready to try such a “cure.” The preparations
appear to be nothing more than concentrated solutions of sugar. It
is probable that a small amount of the cane sugar might be inverted
to glucose and fructose, but experiments have shown that cane sugar
subcutaneously administered in the small amounts used in this
instance is largely excreted in the urine unchanged. Less is known
about galactose, but the evidence available would indicate that
galactose is largely excreted in the urine unchanged when given
subcutaneously. Glucose would be absorbed as such, and in the amounts
under consideration, used by the system much the same as when given by
mouth.--(_From The Journal A. M. A., Aug. 21, 1920._)
SUPSALVS NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
declaring Supsalvs (Anglo-French Drug Company) inadmissible to New and
Nonofficial Remedies.
W. A. Puckner, Secretary.
Supsalvs are advertised by the Anglo-French Drug Company as “stable
suppositories of ‘606’ (of French manufacture)” with the claim that
by the rectal administration of these suppositories the effects of
arsphenamine may be obtained. The asserted efficacy of Supsalvs
medication is based in part on the claim that for these suppositories
an excipient was found which mixes with the cocoa butter base “to form
an assimilable emulsion.”
“The active principle and the vehicle being bound to one another,
the mucous membrane is able to absorb both simultaneously and
progressively in the form of an organic emulsion.”
As no information was furnished the Council by the Anglo-French Drug
Company on the origin or quality of the arsphenamine used in the
preparation of Supsalvs or the character of the vehicle which was
“bound” to the arsphenamine in such a way as to permit the absorption
of this combination in the form of an “organic emulsion,” the firm
was requested to furnish: (1) Evidence that the arsphenamine used in
Supsalvs complies with the N. N. R. standards and that deterioration
of it does not occur in the preparation of the suppositories or on
keeping. (2) The identity of the ingredients composing the suppository.
The Anglo-French Drug Company did not supply the requested evidence
and consequently the Council judged the preparation on the basis of
the information received from the company, and that contained in the
available advertising and circulars. It found Supsalvs inadmissible
to New and Nonofficial Remedies, first because the quality of the
medicament contained in the suppositories has not been established, and
second because the claimed efficacy of this preparation as a means of
securing the effects of arsphenamine lacks substantiating proof.
During the past few years some French physicians have reported
favorably on the intrarectal administration of arsphenamine. Boyd and
Joseph at Panama published (The Journal, Aug. 17, 1918, p. 521) an
enthusiastic report on intrarectal injection of arsphenamine but did
not refer to its use in the form of suppositories. In a comprehensive
report, on the “Treatment of Syphilis” (_Quarterly Journal of Medicine,
July, 1917_) L. W. Harrison stated that arsphenamine (Salvarsan) in the
shape of an enema is definitely less effective than intravenously and
that “Neisser and the vast majority of workers can see no value in the
rectal method.” Schamberg and Hirschler (A Safe and Efficient Intensive
Method of Treating Syphilis, _Therapeutic Gazette_, November, 1919,
p. 761) have given a rather thorough trial of this method; the results
were most disappointing: “A certain or rather uncertain amount of
arsphenamine is absorbed into the blood, but the quantity is obviously
too small to be at all comparable in its effect with the intravenous
administration. Our conclusions are that the rectal administration
of arsphenamine or neoarsphenamine is an extremely feeble method of
administering these drugs.”
The report of the Special Committee on the Manufacture, Biological
History and Clinical Administration of Salvarsan and Other Substances
of the British National Health Insurance Medical Research Committee
contains the following: “The rectal method of administration, either in
the form of solution or as suppositories, has been advocated by a few
observers mainly for cases in which there is difficulty in the adoption
of the intravenous method. The experiments made by Mills at Rochester
Row show that three enemata of ‘606’ (0.6 Gm. in each) on successive
days failed to produce any effect on the spironemes in the lesions.
The general opinion of experienced workers is that the rectal method
is ineffective, and in this view the Committee concur.”--(_From The
Journal A. M. A., Oct. 30, 1920._)
HYPODERMIC SOLUTION NO. 13, IRON, ARSENIC AND PHOSPHORUS
COMPOUND NOT ACCEPTED FOR N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
Hypodermic Solution No. 13, Iron, Arsenic and Phosphorus Compound
(Burdick-Abel Laboratory) is said to contain in each c.c.:
Ferrous citrate 0.06 Gm.
Sodium cacodylate 0.06 Gm.
Sodium glycerophosphate 0.1 Gm.
Chloretone 0.005 Gm.
The preparation is advertised as “the old reliable hematinic” which is
“indicated in all forms of anemia, where both red and white cells are
low.” It is for hypodermic or intramuscular administration. The product
is inadmissible to New and Nonofficial Remedies because:
1. It does not contain ferrous citrate as claimed. Instead the iron is
in the ferric condition, apparently in the form of the unofficial and
unstandardized “iron citrate green” for which there is no evidence of
superiority over the official iron and ammonium citrate.[134]
[134] Iron Citrate Green, The Journal A. M. A., Jan. 12, 1917, p. 135;
Reports Council Pharm. and Chem., 1916, p. 42.
2. Its name gives no information on the form in which the iron, the
arsenic and the phosphorus occur therein. The term “arsenic” does
not indicate whether the mild cacodylate or the potent arsenous
oxid is being administered nor does the term “phosphorus” tell the
physician that he is administering the practically inert sodium
glycerophosphate.[135]--(_From The Journal A. M. A., Nov. 13, 1920._)
[135] Glycerophosphates, The Journal A. M. A., Sept. 30, 1916,
p. 1033; Reports Council Pharm. and Chem., 1916, p. 32. Sodium
glycerophosphates. Reports Council Pharm. and Chem., 1916, p. 52.
PARATHESIN NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
The local anesthetic ethyl paraminobenzoate was first introduced as
“Anesthesin” or “Anæsthesin.” Ethyl paraminobenzoate is not patented
in the United States and it may be manufactured, therefore, by any
firm which chooses to do so. In order that a common name by which to
designate the drug might be available, the Council coined the name
“Benzocaine,” as being short and easily remembered, but yet suggestive
of its composition and character (“benzo” to indicate its derivation
from benzoic acid and “caine” to indicate its cocaine-like properties).
As the term “anesthesin” had become a common name for the drug, the
Council recognized this as a synonym for benzocaine.
One of the accepted brands for benzocaine is “Anesthesin,”
manufactured by the H. A. Metz Laboratories, Inc. (see New and
Nonofficial Remedies, 1920, p. 33). However, on April 19, 1920, the
Metz Laboratories requested that its product be recognized under
the designation of “Parathesin.” As the use of one substance under
several names causes confusion and retards rational therapeutics, the
Council’s rules provide against the recognition of proprietary names
for nonproprietary, established drugs. In view of this and because
the legitimate interests of the manufacturer may be safeguarded
by appending his name or initials to the common name, benzocaine
or anesthesin, the Council voted not to recognize the designation
“Parathesin.”--(_From The Journal A. M. A., Nov. 13, 1920._)
CHLORLYPTUS
Report of the Council on Pharmacy and Chemistry
The condensed report on Chlorlyptus which follows and also a complete
detailed report was sent to the proprietor, Jan. 9, 1920. In reply
he requested that publication be postponed pending the submission of
further clinical evidence. As after nine months this evidence had not
been received the Council has authorized publication of its report.
W. A. Puckner, Secretary.
Chlorlyptus is manufactured by Chas. A. Weeks, trading as the Weeks
Chemical Company, Philadelphia. It is prepared by chlorinating
eucalyptus oil until it has bound 30 per cent. of chlorin, the chlorin
being in relatively stable combination. It is claimed that Chlorlyptus
is a new “chlorinated antiseptic,” highly efficient as a wound
antiseptic and at the same time nonirritant and nontoxic. Chlorlyptus
is offered for use in the treatment of local infections of all types,
as well as of burns, and also as an antiseptic in the alimentary and
genito-urinary tracts.
The claims were based largely on reports of investigations made by
Philip B. Hawk and his collaborators. These reports the referee
of the committee in charge of Chlorlyptus considered incomplete
and unconvincing. Being advised of this Mr. Weeks caused further
investigations to be made. Some of the information was checked and
extended by the A. M. A. Chemical Laboratory and by the referee.
The laboratory side of the investigation may now be considered as
complete. The results show that Chlorlyptus is a feeble antiseptic of
the aromatic oil type, considerably weaker than eucalyptus oil, both
as to therapeutic and toxic qualities. The chlorin contained in it is
bound too firmly to have any action; in fact, the chlorination appears
to have accomplished nothing more than a considerable destruction or
weakening of the eucalyptus oil. As far as the referee can judge, this
object could have been accomplished just as effectively by diluting
ordinary eucalyptus oil with some indifferent solvent.
The manufacturer of Chlorlyptus contends that if the experimental
findings are against his product, it should be judged by the clinical
data. The clinical evidence, however, is not decisive. It shows that
wounds healed and infections were prevented or successfully combated in
cases in which Chlorlyptus was used in combination with good surgery,
but it does not show how much of the result was due to the surgery and
how much, if any, to the use of Chlorlyptus. Even if it were granted
as probable that the Chlorlyptus contributed to the favorable outcome,
it would still be a question whether it equals other established
antiseptics, or whether it possesses any material advantages over
diluted eucalyptus oil. Until these points are established the clinical
reports cannot offset the unfavorable results of the laboratory
investigation.
The manufacturer has endeavored to obtain more convincing clinical
reports, but the lack of success in this direction during the past nine
months gives little encouragement that acceptable clinical evidence
will be available within a reasonable time.
Believing that the information which has been obtained should be made
available to the profession, the Council authorized publication of
this statement and also of the detailed report. The Council voted not
to accept Chlorlyptus for New and Nonofficial Remedies because of the
unfavorable results of the laboratory investigation, but with the
agreement that the product would receive further consideration should
more convincing clinical data become available.
I. DETAILED REPORTS
Summarized Reports
CHEMICAL NATURE OF CHLORLYPTUS
Chlorlyptus is prepared by chlorinating eucalyptus oil until it
has bound 30 per cent. of chlorin. “Chlorlyptol” is prepared in an
analogous manner from eucalyptol. There has been some confusion as to
the composition; but the principal constituent is now stated to be “a
dichloride of eucalyptus oil,” to which the formula C₁₀H₁₆OCl₂ has
been assigned. It differs from the “chlorinated eucalyptus oil,” as
ordinarily used for making dichloramin-T solutions, and which contains
only 2/3 per cent. of chlorin.
AVAILABILITY OF CHLORIN IN CHLORLYPTUS
The chlorin content of chlorlyptus is almost entirely firmly bound,
and therefore not “available,” in contrast to the group of so-called
chlorinated antiseptics (i. e., the hypochlorite and chloramin type).
For instance, it does not directly liberate iodin from iodid. It
contains a very small quantity of free hydrochloric acid, or perhaps
some acid esters, and liberates a little more on prolonged contact with
water; but the total quantity liberated under reasonable conditions is
very small. According to Hawk’s data, they correspond only to 1/8 per
cent. HCl even after standing with water overnight and to only 1/5 per
cent. of HCl after two weeks. The referee has shown that this quantity
of acid has no therapeutic significance.
The “bound” chlorin of chlorlyptus, being chemically inactive, would
have no more practical significance than the bound chlorin in common
salt. The “ozone” said to be used during the preparation, to expel the
HCl, has also practically disappeared, to judge by the slowness with
which iodin is liberated from potassium iodid.
ACID FORMATION
Some constituents of chlorlyptus hydrolyze slowly and to a slight
degree with the liberation of a trace of free hydrochloric acid.
According to the data of Hawk’s report, the free acidity, in term
of HCl, is 1/12 per cent. On standing with water over night, this
increases to 1/8 per cent.
On this basis, Hawk proposed a theory that the claimed antiseptic
effects of chlorlyptus are due to the continuous liberation of
hydrochloric acid.
Experiments by the referee show this to be untenable. The traces of
acid are neutralized and absorbed by the tissues so rapidly that an
acid reaction is not maintained. These experiments are described in the
appendix.
They were submitted to the manufacturers, who in the name of Mr. Weeks
(May 9, 1919) concede this conclusion and state that “there is no
doubt that the referee’s statements as to action in mouth, contact
with living tissue and improbability that the acidity is effectively
antiseptic is correct, and I am willing to accept the referee’s
statement as conclusive in this respect.”
BACTERIAL CULTURE EXPERIMENTS
Mr. Weeks submitted a statement by Hawk to the effect that chlorlyptus
has a phenol coefficient of 2.6, determined by the standard Hygienic
Laboratory procedure.
He also quotes Rockefeller War Hospital that chlorlyptus kills
_Staphylococcus aureus_ in concentra of 1 dram: 1 gallon (about
1:1,000), but not in more dilute solutions.
More recently, he presented a more comprehensive report by Rivas, which
is reproduced in the appendix. The essential results are tabulated
herewith. This tabulation shows that chlorlyptus fails to kill the
organisms after an hour’s exposure of the following concentrations:
Typhoid in bouillon, 10 per cent. of chlorlyptus.
Staphylococci in pus, 5 per cent. of chlorlyptus.
Staphylococci in serum, 1 per cent. of chlorlyptus.
It seems to the referee that a substance that is ineffective with an
hour’s exposure to these concentrations is not at all likely to kill or
check bacteria under clinical conditions. In other words, it is not an
antiseptic in the ordinary sense.
The referee is not impressed by the superior power attributed by Rivas
to chlorlyptus in the presence of pus. Inefficiency of 10 per cent. for
one-half hour or of 5 per cent. for two hours seems a failure rather
than a success. The referee also notes the absence of any data as to
the relative efficiency of chlorlyptus against staphylococci in pus and
in bouillon. The data on serum indicate that chlorlyptus is much weaker
than phenol and show that it is _less effective in the presence of pus_
than in other mediums.
The referee fails to grasp the bearing of the oil experiments on any
clinical condition. Moreover, the inconstant results mentioned by Rivas
suggest the possibility that the incorporation of the bacteria in oil
may have prevented their effective distribution in the culture medium.
If any significance is to be attached to these experiments, they should
be checked by controls, without antiseptics.
SUMMARY OF RIVAS’ IN VITRO EXPERIMENTS
====================================================================
Minimal Maximal
Germicidal Not Germicidal
Concentrations Concentrations
Typhoid Bacilli in Bouillon:
Chlorlyptus (Exp. 3) 10%, 2 to 4 hours 10% for 1 hour
5% for 2 hours
Eucalyptus oil (Exp. 1) 5% within 5 minutes No data
Phenol (Exp. 5) 1% within 10 min. No data
Streptococci and Staphylococci in Olive Oil:
Chlorlyptus
(Exps. 7 and 8) 1%, almost at once, No data
sometimes
Eucalyptus oil No data No data
Phenol (Exps. 9 and 10) 1%, almost at once, No data
Staphylococci in Pus:
Chlorlyptus (Exp. 11) 10% for 1 hour 10% for 1/2 hour
5% for 2 hours
Eucalyptus oil No data No data
Phenol No data No data
Staphylococci in Human Blood Serum:
Chlorlyptus (Exp. 12) 5% in 1 hour 1% in 1 hour
Eucalyptus oil No data No data
Phenol 5% almost at once 1% in 1 hour
--------------------------------------------------------------------
INFECTION EXPERIMENTS IN VIVO
Dr. Rivas reports two series of experiments, in each of which three
guinea-pigs received staphylococcus suspensions in the peritoneum.
One guinea-pig in each series was left untreated; the others received
injections of chlorlyptus into the peritoneum at various intervals.
The following results were obtained:
====================================================
Chlorlyptus Results
Exp. 19, No. 1 None Survived
Exp. 20, No. 1 None Died
Exp. 19, No. 2 At once Died
Exp. 19, No. 3 After 24 hours Survived
Exp. 20, No. 2 After 18 hours Died
Exp. 20, No. 3 After 24 hours Died
----------------------------------------------------
This shows mortalities of:
1 in 2, i. e., 50 per cent., without chlorlyptus.
3 in 4, i. e., 75 per cent., with chlorlyptus.
It is doubtful whether so small a series of experiments on so variable
a phenomenon as is infection should receive any serious consideration.
So far as they go, they would indicate that chlorlyptus is useless or
worse.
TOXICITY
The referee determined the acute toxicity of chlorlyptus by hypodermic
injection of oily solutions into white rats. Comparative experiments
were made with ordinary eucalyptus oil. The details are given in the
appendix. The end-results may be summarized as follows:
==================================================================
Survived Chlorlyptus Eucalyptus Oil
1.56 c.c.
3.75 c.c.
5.00 c.c.
6.25 c.c. 1.25 c.c.
8.65 c.c. 2.5 c.c. (3 days)
Died (in days) 12.5 c.c. (1 day) 3.75 c.c. (3 days)
12.5 c.c. (1 day) 5.00 c.c. (3 days)
18.75 c.c. (1 day) 6.25 c.c. (1-1/2 days)
M. F. D. 8.75 to 12.5 c.c. per kg. 1.25 to 2.5 c.c. per kg.
------------------------------------------------------------------
_Fatality._--The doses are calculated for cubic centimeters of the
undiluted drugs per kilogram of rat.
Dr. Rivas reports a series of toxicity experiments on guinea-pigs.
Assuming a uniform weight of 400 gm. per animal, his results (details
in appendix) may be summarized as:
==================================================================
Minimal Maximal
Fatal Dose Survived Dose
C.c. per Kg. C.c. per Kg.
Chlorlyptus, peritoneal (Exp. 14) 7.5 c.c. 5.0 c.c.
Chlorlyptus, pleural (Exp. 15) 5.0 c.c. 2.5 c.c.
Eucalyptus oil, peritoneal (Exp. 16) 2.5 c.c. No Data
Eucalyptus oil, pleural (Exp. 16) 1.25 c.c. No Data
Dichloramin-T, peritoneal (Exp. 16) 1.25 c.c. No Data
------------------------------------------------------------------
The _comparative toxicity_ in the various series is therefore
approximately as follows:
========================================================
Chlorlyptus : Eucalyptus
Referee, rats, hypodermic 1/5 : 1
Rivas guinea-pig, peritoneal 1/3 : 1
Rivas guinea-pig, pleural 1/4 : 1
--------------------------------------------------------
Evidently, the toxicity of chlorlyptus is about one-fourth of that of
eucalyptus oil. The difference is considerable, but not fundamental.
Moreover, the symptoms of chlorlyptus resemble the characteristics of
eucalyptus oil.
According to the tabulation of Barker and Rowntree,[136] the mean fatal
dose of eucalyptus oil for man, in the twenty-nine clinical cases
reported in the literature, is about 20 c.c. If the toxicity ratio of
the two substances were the same as for the rat experiments (a rather
hazardous assumption), the fatal dose of chlorlyptus for man would be
about 80 c.c.
[136] Barker and Rowntree (Bull. Johns Hopkins Hospital =29=:215, 221
[Oct.] 1918) obtained the following results with eucalyptus oil:
Cat, hypodermic; survived 3 c.c. per kg.; killed by 5.5 c.c. per kg.
Cat, intraperitoneal; killed by 5 c.c. per kg.
Dog, hypodermic; survived 1.3 c.c. per kg.
They quote from Browning that the following doses, c.c. per kilogram,
are not fatal: frogs, 0.5; rabbits, 1 to 5; guinea-pigs, 1.
IRRITATION
Rivas’s Experiment 14 shows that chlorlyptus gives very definite
irritation, apparently similar to that produced in Experiment 16 by
eucalyptus oil in one-fourth the dose.
Incidentally, the referee may add from personal experience that the
“chlorlyptus oil, 5 per cent. Cl” is markedly irritating in the
nostrils, although marked “non-irritating” on the label.
II. APPENDIX: SPECIAL REPORTS
A. COMPARISON OF CHLORLYPTUS WITH CHLORINATED EUCALYPTOL
From the Chemical Laboratory of the American Medical Association
According to the label, “Chlorlyptus” is a “Synthatized Chlorinated
Oil of Eucalyptos, with Acid Reaction, containing approximately 30
per cent. Chlorine and possesses excellent Germicidal Properties,
when made under our special process.” It is manufactured by the Weeks
Chemical Company, Philadelphia, Pa. This product was submitted to the
Council on Pharmacy and Chemistry by the manufacturers, and in turn
the Laboratory was asked to examine it with the idea of comparing it
with the nonproprietary brands of “chlorinated eucalyptol” (used as a
solvent for dichloramine-T; see New and Nonofficial Remedies, 1919,
p. 70). In the submission, certain tests were described, most of which
were followed. Among the statements given under the chemical properties
of chlorlyptus are:
“On distillation, chlorlyptus begins to boil at about 100 C. The
temperature rises as the distillation continues, accompanied by the
decomposition of the chlorlyptus and the evolution of hydrochloric
acid and chlorine.”
“When brought into contact with water, chlorlyptus undergoes a
process of hydrolysis ...”
Notwithstanding the foregoing the statement is made on the label that
chlorlyptus “is a Stable Compound, not affected by heat, light or
water.”
The following comparisons of chlorlyptus, chlorinated eucalyptol-Abbott
and chlorinated eucalyptol-Squibb were made:
Chlorlyptus is a viscous, dark brown liquid, with an acrid odor and
having a specific gravity of 1.2098. Chlorinated eucalyptol-Abbott is a
mobile, light yellow liquid, with a eucalyptus odor, having a specific
gravity of 0.9317. Chlorinated eucalyptol-Squibb is a mobile, colorless
liquid, and its specific gravity is 0.9303.
An alcoholic solution of silver nitrate added to an alcoholic solution
of chlorlyptus yields a heavy precipitate of silver chloride. In the
case of the Abbott chlorinated eucalyptol a slight turbidity is caused
by this test; the Squibb product shows no reaction.
A 10 per cent. solution of potassium iodide is overlaid with an equal
volume of chlorlyptus. Iodine is slowly liberated, being noticeable
in one-half hour. With chlorinated eucalyptol-Abbott, a trace of
free iodine is discernible after four hours, while with chlorinated
eucalyptol-Squibb there is no free iodine present. When the respective
products are shaken with an alcoholic solution of potassium iodide, no
iodine is immediately liberated, thus showing the absence of “active
chlorine” (difference from the hypochlorite derivatives).
When chlorlyptus is dissolved in concentrated sulphuric acid, some
blackening occurs and the odor of hydrogen chloride is very noticeable.
Both the Abbott and Squibb brands of chlorinated eucalyptol give a
reddish mixture, with no perceptible evolution of hydrogen chloride,
and still retain the characteristic eucalyptol odor.
On heating, chlorlyptus decomposes and begins to boil at from 103 to
105 C. Then a higher fraction comes over at 178 C. The distillate has
a sharp odor, is acid, and frees very little iodine from potassium
iodide. Chlorinated eucalyptol-Abbott does not seem to decompose. Some
gaseous substance is given off at 80 C, but the liquid distills at
173 C. The distillate has no acid odor, is neutral, and liberates no
iodine from potassium iodide. (In both cases the distillation was not
carried to completion, approximately only about half of the volume
being distilled over.)
PRELIMINARY TESTS ON CHLORLYPTUS AND CHLORINATED EUCALYPTOL
======================================================================
Chlorinated Chlorinated
Chlorlyptus Eucalyptol-Abbot Eucalyptol-Squibb
Odor Acrid Like eucalyptus Like eucalyptus
Density and Dark brown; Light yellow; Colorless;
color viscous, mobile; lighter mobile; lighter
heavier than water than water
than water
AgNO₃ added Heavy ppt. Slight turbidity Clear
to alcoholic
solution
Equal parts Gives free Gives free iodin No free iodin
with KI iodin slowly, in 4 hours; in 4 hours
solution noticeable not much
in 1/2 hour
Equal parts Much iodin Small amount of No free iodin
with 10% KI, immediately free iodin in in 3 hours
10% KIO₃ few numbers;
solution does not
noticeably
increase
Equal parts Some blackening; Reddish mixture; Same
with conc. odor of HCl no HCl;
H₂SO₄ eucalyptol odor
Alcohol KI No iodin Same Same as Abbott
liberated product
Heating Decomposes and Apparently does not
boils at decompose; some
103-105 C.; gas given off
then higher when T=80; the
fraction comes liquid distilled
over at 178 C.; at 173 C.; the
distillate has distillate did
sharp odor, is not have much
acid, but frees odor; no HCl
very little gas detected;
I₂ from KI; no I₂ from
distillation KI; distillate
not completed was neutral
(distillation
not completed)
----------------------------------------------------------------------
The addition of chlorlyptus to a mixture of 10 per cent. potassium
iodide, 10 per cent. potassium iodate solution, brings about the
liberation of iodine, increasing perceptibly on standing. This shows
that the hydrogen chloride is gradually split off, and in time will
cause a solution having a considerable degree of acidity. When this
test is carried out on chlorinated eucalyptol-Abbott, a small amount
of iodine is liberated in a few minutes but does not increase, showing
a slight initial acidity without further hydrolysis. Chlorinated
eucalyptol-Squibb yields no free iodine after standing three hours.
When the chlorine content of chlorlyptus is determined according to
the method of Carius, the amount is found to be 29.6 per cent. (The
manufacturers give a method of determining chlorine by Hunter’s fusion
method. It is believed that in this method hydrogen chloride may
be lost, and this opinion is substantiated by the firm’s statement,
“Chlorlyptus analyzed in this manner shows approximately 25 per cent.
of chlorine.”) The chlorine content of chlorinated eucalyptol-Abbott is
found to be 0.67 per cent., and that of the Squibb brand to be 0.62 per
cent. (about one-fiftieth as much as in chlorlyptus).
To sum up: Chlorlyptus differs from chlorinated eucalyptol in odor,
color, density, in reaction to silver nitrate, potassium iodide,
sulphuric acid and the aqueous solution of potassium iodate and
potassium iodide. The distillation of the two products occurs
differently. Chlorlyptus contains nearly 30 per cent. of chlorine,
which is approximately fifty times as much as in chlorinated
eucalyptol. Thus it appears to have considerable chlorine in the
negative form (Cl^-) which may be relatively easily split off as
hydrogen chloride.
B. THE PERSISTENCE OF THE ACID
Reaction of Chlorlyptus in the Body
BY THE REFEREE
This “chlorinated ozonized eucalyptus oil” is distinctly acid to litmus
paper. It is claimed that further quantities of acid are liberated on
contact with water. This is credited with producing a continuous acid
reaction on the surface of tissues to which the oil may be applied and
this in turn is stated to be antiseptic or germicidal.
This theoretical speculation does not take into account the large
quantity of reserve alkali in the body by which it combats attempts to
alter its normal reaction. It is therefore not convincing, unless it is
supported by direct evidence.
In the absence of such data on the part of the promoters of the
preparation, experiments were made to determine whether the oil
preserves its acid reaction in contact with mucous and serous
membranes. The answers were clearly in the negative.
In the mouth, the reaction becomes neutral within ten or fifteen
minutes; in the pleura and peritoneum within half an hour, and probably
in much shorter periods.
More detailed data follow:
SERIES A: BEHAVIOR IN THE MOUTH; HOMO
EXPERIMENT.--Chlorlyptus and to less extent Chlorlyptus Oil, are acid
to litmus. They are applied:
(_a_) Drop to litmus paper and this to gums.
(_b_) Several drops directly to tongue.
(_c_) Same to gums.
The reaction to litmus paper is tried from time to time.
RESULTS.--(_a_) Applied to gums on litmus paper:
Chlorlyptus: Red color becomes gradually feebler and does not spread on
the paper.
Chlorlyptus Oil: Turns blue in a few minutes.
(_b_) Dropped on _tongue_:
Chlorlyptus: Acid taste at once. Does not increase, but on contrary,
becomes less.
Litmus applied after ten minutes: not acid.
Litmus applied after five minutes: distinctly acid.
(_c_) Dropped on inside of _cheek_:
Chlorlyptus, 1/3 c.c.: After six minutes, litmus very red.
After ten minutes, faintly red.
After fifteen minutes, blue.
Chlorlyptus Oil, 1 c.c.
After three minutes, faintly red.
After eight minutes, neutral.
CONCLUSIONS.--On contact with living tissues, the acid of chlorlyptus
is rapidly neutralized and absorbed.
The surface is neutral within ten or fifteen minutes.
It is therefore very improbable that the acidity is effectively
antiseptic.
A comparison of chlorlyptus with dilute acetic acid shows that the
chlorlyptus does not maintain the acidity even as well as 1 per cent.
acetic acid.
=====================================================================
Acetic Acid Chlorlyptus
Tongue, a drop of 5 per cent.; still Neutral between five
slightly acid to litmus after ten minutes; and ten minutes
taste almost gone in two minutes
Gums, a few drops between cheeks and gums: Neutral between ten
Five per cent. still strongly acid in and fifteen minutes
twelve minutes; distinctly acid in
seventeen minutes. One per cent. still
strongly acid in twenty-one minutes
---------------------------------------------------------------------
CHLORLYPTUS: REACTION (LITMUS PAPER) ON CONTACT WITH TISSUE
======================================================================
Serial When Quantity, Time Blue Symptoms or
No. Animal Injected C.c. of Death Litmus Toxicity
1 Rat Pleura 1 1/2 hour Remains blue None; killed;
pleura not
congested;
lung spec. =
21; slight
congestion
2 Rat Pleura <1 1 hour Remains blue Negative
3 Rat Pleura 1 23 min. Remains blue Almost at once
bad gasping
respiration
and died in
23 m.; heart
distend.;
possibly
injection
penetrated
lung
Peritoneum 1 23 min. Turns red
4 Rabbit Pleura 1 .... ...... Died
overnight
5 Dog Pleura 1 1/4 hour Remains blue
20 m. p. m.
Peritoneum 1 1/4 hour Remains blue
20 m. p. m.
6 Dog Pleura 1 3 min. Remains blue
45 m. p. m.
Peritoneum 1 3 min. Remains blue
45 m. p. m.
7 Dog Pleura 1 20 min. Remains blue
20 m. p. m.
Peritoneum 1 20 min. Remains blue
20 m. p. m.
SERIES B: SEROUS MEMBRANES
In these experiments, 1 c.c. of chlorlyptus was injected into the
pleura or peritoneum. After a stated time, the animal was killed, and
the reaction of the pleural or peritoneal surface was tested with blue
litmus paper. The results are shown in the table.
C. TOXICITY EXPERIMENTS
By the Referee
TECHNIC
White rats were injected hypodermically with chlorlyptus or with
eucalyptus oil, diluted with olive oil in the ratio of 1:4. The larger
doses were divided between two or more sites of injection.
DETAILED PROTOCOLS
Hypodermic injections in white rats. Drugs diluted with 3 parts of
olive oil. Doses are given as cubic centimeters of pure drug per
kilogram of rat.
A. EUCALYPTUS SERIES
EXPERIMENT 1.--_1.25 c.c._; injected VII.9.19: Active; walks about.
No depression at any time. VII.10.19. Appears normal.
EXPERIMENT 2.--_2.5 c.c._; injected VI.30.19: Quiet--not very
depressed, reflexes good (six hours).
VII.1.19--Active--reflexes good, eats moderately.
VII.2.19--Animal acts normal--eats moderately, reflexes good; active
(a.m.). Later in day, depressed.
VII.4.19--Died during night of VII.3.19.
EXPERIMENT 3.--_3.75 c.c._; injected VI.24.19: Quiet; depressed;
pain reflex diminished. Animal lay on ventral surface, not supported
by legs. Will get on to feet very sluggishly if turned on side
(twenty-four hours). Does not eat.
VI.26.19--Depressed slightly; pain reflex present.
VI.27.19--Fairly active; eats a little.
VI.28.19--Depressed.
Died during night of VI.29.19 (three days).
EXPERIMENT 4.--_5 c.c._; injected VI.24.19: Quiet; markedly depressed
(one hour). Does not get on feet when turned on side; ataxia well
marked. Slight watery secretion in eyes. Reflexes diminished. Does
not eat (twenty-four hours).
VI.26.19--Heart slowed and arrhythmic. Animal lies on side. Unable to
walk; markedly depressed.
VI.27.19--Lies on side; does not eat. Died during night of VI.27.19
(three days).
EXPERIMENT 5.--_6.25 c.c._; injected VI.24.19: Quiet; very markedly
depressed. Heart and respiration greatly slowed. Lies on side; tears
in eyes; does not eat (twenty-four hours).
VI.25.19--Temperature subnormal; cold to touch; tail stiffened and
straight.
Died during night of VI.25.19 (one and one-half days).
Postmortem: Lungs congested. Liver pale in color. Spleen very dark
red. Kidneys normal. Other organs normal.
B. CHLORLYPTUS EXPERIMENTS
EXPERIMENT 1.--_1.56 c.c._; injected VI.24.19: Rather restless for an
hour. Active during next four hours and following twenty-four. Eats
well, reflexes good. Acts normal on VII.1.19 and since VI.26.19.
EXPERIMENT 2.--_3.75 c.c._; injected VI.24.19: More quiet; active
during next twenty-four hours. Reflex all right. Eats well; normal
VII.1.19, since VI.26.19.
EXPERIMENT 3.--_5 c.c._; injected VI.24.19: Quiet; defecation in four
hours. Rather quiet for six hours. Eats well. Reflexes good; normal
VII.1.19, since VI.26.19.
EXPERIMENT 4.--_6.25 c.c._; injected VI.24.19: Quiet and breathing
labored in four hours; active after twenty-four hours. Eats well.
Somewhat depressed on VI.26.19; pain reflex present. On VI.26.19,
eats well and fairly active. Active and eats, VI.27.19. Appears
normal, VII.1.19.
EXPERIMENT 5.--_8.75 c.c._; injected VI.30.19: Rather quiet during
next two hours. Morning of VII.1.19, lies on stomach; quiet; does not
eat very much. Pain reflexes good. VII.2.19, still depressed; does
not eat. Appears normal, VII.3.19.
EXPERIMENT 6.--_12.5 c.c._; injected VI.25.19: Quiet, but reflexes
good; more quiet and depressed after several hours. Some loss of oil
from wound. Died night of VI.25.19 (one day). Tail stiff. Temperature
low.
Postmortem: Lungs markedly congested. Spleen and liver dark red. One
kidney congested. Other viscera normal.
EXPERIMENT 7.--_12.5 c.c._; injected VII.9.19: Quiet for one-half
hour; 1.5 hours twitching of muscles of whole body, lies on side,
ataxia present. Died night of VII.9.19 (one day).
EXPERIMENT 8.--_18.75 c.c._; injected VI.25.19: Quiet; reflexes good
(three hours). Some loss of oil. Depressed and turns on side (six
hours). Died night of VI.25.19 (one day).
Postmortem: Lungs congested. Spleen and liver very dark red. Right
kidney much darker red. Viscera normal.
D. REPORT OF DR. D. RIVAS
The following are the results of experiments conducted by me, during
the past four months, on the germicidal action of chlorlyptus
(chlorinated oil of eucalyptus, principal constituent C₁₀H₁₇OCl₂) in
vitro and in vivo, and comparison also with carbolic acid, oil of
eucalyptus and dichloramine in test for irritation and toxicity.
_Germicidal Action._--Based on the results obtained, chlorlyptus when
used in a 5 per cent. paraffin oil solution was found to be a mild
germicidal against typhoid B, streptococcus and staphylococcus when
these organisms were suspended in ordinary bouillon culture or sterile
salt solutions.
The germicidal action was found stronger when these micro-organisms
were suspended in a sterile oily or lipoid substance, such as olive
oil. The results of these experiments were not constant, owing probably
to the imperfect suspension of the bacteria. Thus, while in some of the
experiments chlorlyptus in 1 per cent. oil solution destroyed these
micro-organisms, in other cases the same strength solution failed to
give same result in same time.
The increased germicidal action of chlorlyptus on bacterial suspensions
in olive oil may be accounted for by the fact that chlorlyptus is
soluble in olive oil and not an admixture, as in the case of paraffin
oil.
Chlorlyptus is not a coagulant, as are germicides of the phenol or
hypochlorite types, and the germicidal action is therefore not strictly
comparable.
The germicidal action of chlorlyptus oil solution, on pathogenic
bacteria, on streptococcus and staphylococcus, suspended in pus, was
found to be stronger than when these micro-organisms were suspended
in ordinary bouillon culture or sterile salt solution. In one of the
experiments, similar results were obtained when these micro-organisms
were suspended in olive oil, chlorlyptus showing marked germicidal
action.
_Irritation and Toxicity._--The irritating action was found to be
relatively mild in tests on laboratory animals. Thus, from 0.5 to
1 c.c. of chlorlyptus in paraffin oil 5 per cent. solution, injected
into peritoneal or pleural cavities of guinea-pigs weighing 400 gm. was
found to be without any appreciable disturbance in the health of the
animal, and in some cases the injection of as much as 2 c.c. did not
kill the animal.
_Therapeutic Action._--Guinea-pigs were inoculated with purulent
material containing streptococcus, staphylococcus and _B. coli_ in
peritoneal and pleural cavities respectively, and after six hours
1 c.c. of chlorlyptus 5 per cent. in paraffin oil solution was
injected. Other infected animals were similarly treated twenty-four
hours after inoculation, and another series forty-eight hours after
inoculation. In some of these cases the animals died from shock but
in a clearly defined series in which the injection of 1 c.c. of the
chlorlyptus solution was made in the peritoneum of the guinea-pigs
twenty-four hours after the inoculation, the animals lived. The control
animal, inoculated with the purulent material and not treated with
chlorlyptus oil solution, died.
In consideration that the injection of chlorlyptus oil solution [sic,
referee] were made [? referee] in the peritoneal cavity this substance
is apt to affect the vital organs in the abdominal cavity. It is
my belief that in case of wall abscess of chronic inflammation, by
limiting the action of chlorlyptus to the infected area, preventing at
the same time the infection of the vital organs, chlorlyptus, because
of its non-irritating quality, can be used effectively as an antiseptic.
CONCLUSIONS
1. Chlorlyptus is a mild and relatively nonirritating antiseptic of
marked action on pus and suppuration.
2. When bacteria were suspended in olive oil or in pus, chlorlyptus
showed marked germicidal action.
3. Chlorlyptus can be injected into the peritoneum or the pleural
cavities of guinea-pigs in the proportion of 1 c.c. per 400 gm. of body
weight without detriment to the animal.
4. Chlorlyptus in 5 per cent. oil solution (taking Clause 3 as
comparison) can perhaps be injected in man as an antiseptic agent when
there is a walled-in abscess in the peritoneum or pleural cavity where
there is drainage, in the proportion of 0.5 to 1 c.c. per pound of body
weight with good result.
REPORT ON THE GERMICIDAL ACTION OF CHLORLYPTUS ON PATHOGENIC
BACTERIA IN VITRO AND IN VIVO
EXPERIMENT 1.--_The germicidal action of eucalyptus oil._--Typhoid
bacillus was destroyed in less than five minutes when exposed to the
action of a 5 per cent. suspension of oil of eucalyptus. The exposure
for four hours in a 5 per cent. suspension of chlorlyptus in paraffin
oil was without effect on typhoid bacillus. It requires an exposure
of two to four hours in a 10 per cent. suspension of chlorlyptus in
paraffin oil to destroy typhoid bacillus.
EXPERIMENT 2.--_Bacilliary action of chlorlyptus on the growth of
pathogenic bacteria._--Typhoid and anthrax bacilli were selected for
the experiment. Two series of five tubes each were made. The culture
medium used was nutrient bouillon. Chlorlyptus was added in the
following proportions: Tube 1, 1:10; Tube 2, 1:100; Tube 3, 1:1,000;
Tube 4, 1:10,000, and Tube 5, 1:100,000. One series was inoculated
with typhoid bacillus. All tubes were incubated for three days at
37 C.
Chlorlyptus inhibited the growth of typhoid bacillus when added
to the bouillon in the proportions of 1:10. The growth of anthrax
bacillus was inhibited by chlorlyptus when it was added in the
proportions of 1:10, 1:100 and 1:1,000, as shown in the accompanying
table. [The table was not submitted.--Ed.] In one instance the growth
was markedly inhibited by chlorlyptus when added in the proportion of
1:10,000.
EXPERIMENT 3.--_Germicidal action of chlorlyptus on typhoid
bacillus._--Bouillon cultures of typhoid bacillus forty-eight hours
old, and a suspension of forty-eight-hour agar cultures of typhoid
bacillus in sterile salt solution were used for the experiment.
Chlorlyptus was added in the proportion of 1:1,000; 1:1,500; 1:100;
2 per cent.; 3 per cent.; 4 per cent.; 5 per cent. and 10 per cent.,
respectively.
Inoculations were made in trypsinized peptone bouillon after the
addition of chlorlyptus at different intervals, namely: at once,
after five minutes, after ten minutes, after fifteen minutes, after
thirty minutes, after one hour and after two hours, and tubes
incubated at 37 C. for forty-eight hours.
Result: Growth was shown in all tubes except those in which
chlorlyptus was added in the proportion of 10 per cent. and after the
action of the antiseptic for two hours or longer.
EXPERIMENT 4.--_Inhibitory action of chlorlyptus in the growth
of typhoid bacillus._--Chlorlyptus was added to sterile bouillon
in the proportion of 1:100, 1:1,000, 1:10,000 and 1:100,000, and
incubated for forty-eight hours at 37 C. to eliminate any possible
contamination of the bouillon during the manipulations. All tubes
were found sterile and inoculated with typhoid bacillus.
Result: All tubes were found sterile again after being inoculated
with typhoid bacillus and incubated at 37 C. for forty-eight hours,
which shows chlorlyptus inhibited and the growth of typhoid bacillus
in bouillon when this antiseptic was added in the proportions of
1:100 to 1:100,000.
Remarks: In another experiment made, chlorlyptus showed a weaker
inhibitory action on the growth of typhoid bacillus.
EXPERIMENT 5.--_Germicidal action of carbolic acid._--The technic was
the same as that outlined in Experiment 1. except that carbolic acid
was used instead of chlorlyptus.
Result: Carbolic acid showed a distinct germicidal action on
typhoid bacillus in the proportions of 1 per cent. in ten minutes.
EXPERIMENT 6.--_Action of nitrogen gas on the growth of typhoid
bacillus in bouillon and nutrient agar when chlorlyptus was added to
this culture medium._--Chlorlyptus was added to the bouillon in the
proportions of 1:100, 1:1,000, 1:10,000 and 1:100,000, as outlined in
Experiment 2; also to agar kept melted at 45 C. Tubes were inoculated
with typhoid bacillus; plates were made of the inoculated agar tubes;
all plates and tubes were incubated at 37 C. for forty-eight hours in
an atmosphere of nitrogen gas.
Duplicate experiments were made with cultures of typhoid bacillus
as above in bouillon and agar plates containing the same amount of
chlorlyptus and incubated at 37 C. in ordinary atmosphere as control.
Result: Nitrogen gas did not show any appreciable increase of the
germicidal action of typhoid bacillus when grown in medium containing
chlorlyptus. Growth was about the same in cultures supplied with
nitrogen gas as in those growing in ordinary atmosphere.
EXPERIMENT 7.--_Germicidal action of chlorlyptus on pyogenic bacteria
suspended in an oily medium._--Experiment with streptococcus:
Cultures of streptococcus in blood agar three days old were suspended
in olive oil (sterile), and chlorlyptus was added in the proportions
of 1, 5 and 10 per cent. and inoculated in trypsinized bouillon at
different intervals, namely: at once, after five minutes, after ten
minutes, after fifteen minutes, after thirty minutes, and after one
hour. Tubes were incubated at 37 C. for forty-eight hours.
Result: All tubes remained sterile. The germicidal action of
chlorlyptus on streptococcus suspended in oil was almost at once and
with certainty after five minutes when added in the proportion of 1,
5 and 10 per cent.
EXPERIMENT 8.--_Germicidal action of chlorlyptus on staphylococcus,
suspended in sterile olive oil._--The technic employed was the same
as in Experiment 5, except that a culture of staphylococcus was used.
Result: All tubes remained sterile. The germicidal action of
chlorlyptus was almost at once in the proportions of 1, 5 and 10 per
cent.
Remarks: By repeating this experiment the result showed some
variations. The discrepancy was probably due to an imperfect
suspension of the micro-organism in the oil.
EXPERIMENT 9.--_Germicidal action of carbolic acid on streptococcus
suspended in olive oil._--The technic employed was the same as
in Experiment 5, except that carbolic acid was used instead of
chlorlyptus.
Result: The germicidal action of carbolic acid of streptococcus
suspended in olive oil was almost at once in the proportions of 1, 5
and 10.
EXPERIMENT 10.--_Germicidal action of chlorlyptus on
staphylococcus._--The technic employed was the same as in Experiment
6 except that the carbolic acid was used instead of chlorlyptus.
Result: The germicidal action of carbolic acid on staphylococcus
suspended in olive oil was almost at once, in proportions of 1, 5 and
10 per cent.
EXPERIMENT 11.--_Germicidal action of chlorlyptus on pyogenic
bacteria suspended in pus._--Chlorlyptus was added to sterile pus in
the proportions of 1, 5 and 10 per cent., and then inoculated with
staphylococcus and cultures were made in bouillon at once, after
five minutes, after ten minutes, after fifteen minutes, after thirty
minutes, after one hour and after two hours, respectively, and tubes
incubated for forty-eight hours at 37 C.
Result: Growth was shown in all tubes except those inoculated from
tubes in which chlorlyptus was added in the proportions of 10 per
cent. after one hour.
EXPERIMENT 12.--_Germicidal action of chlorlyptus on streptococcus
suspended in sterile human blood serum._--Staphylococcus culture
in agar forty-eight hours old was suspended in sterile human blood
serum, and to the suspension chlorlyptus 5 per cent. in paraffin oil
was added in the proportions of 1, 5 and 10 per cent. Inoculations
were made at intervals, at once, after five minutes, after ten
minutes, after fifteen minutes and after one hour in trypsinized
bouillon. Tubes were incubated at 37 C. for forty-eight hours.
Result: Chlorlyptus showed inhibitory action on the growth of
staphylococcus in the strength of 10 per cent., but did not produce
complete sterilization. Similar results were shown with the 5 per
cent., and in the 1 per cent. chlorlyptus did not show any inhibitory
action at all.
EXPERIMENT 13.--_Germicidal action of carbolic acid on staphylococcus
suspended in human blood serum (sterile)._--The technic employed
was the same as in Experiment 10 except that carbolic acid was used
instead of chlorlyptus.
Result: Carbolic acid produced a complete sterilization in the
strength of 10 per cent. almost at once, and with certainty after
five minutes. Similar results were produced with the 5 per cent. The
1 per cent. carbolic acid did not show any appreciable germicidal
action on staphylococcus.
EXPERIMENT 14.--_Toxic and irritant action of chlorlyptus._--Six
normal guinea-pigs were used for the experiment. Guinea-Pig 1 was
injected peritoneally with 1 c.c. of chlorlyptus, Guinea-Pig 2 with
2 c.c. of chlorlyptus, Guinea-Pig 3 with 3 c.c. of chlorlyptus,
Guinea-Pig 4 with 4 c.c. and Guinea-Pig 5 with 5 c.c. 5 per cent.
respectively. Guinea-Pig 6 was used as a control and not injected.
Result: Guinea-Pigs 1 and 2 did not show any appreciable disturbance.
Guinea-Pig 3 was sick for four days, after which it gradually
recovered but it became sick again after one week and died ten days
after the injection. Guinea-Pig 4 died over night. Guinea-Pig 5
died six hours after injection. Guinea-Pig 5 was injected at 11:30
with 5 c.c. chlorlyptus. Ten minutes after the injection it was
lying relaxed, respiration and heart normal, conjunctive reflex
present. One hour after the injection the animal seemed to present
symptoms resembling those of narcosis: respiration and heart were
normal. After four hours there was no change in the condition of the
guinea-pig except that the respiration was irregular. Five and a half
hours after it showed prostration with irregular respiration and
heart action. Six hours after injection the animal was dead.
Autopsy: The peritoneum showed a congestion and a fibrinous
exudation, amount of liquid increased, some part of which was
probably chlorlyptus unabsorbed. Spleen about normal, liver
congested, kidney about normal, suprarenal glands about normal, lungs
normal, pleural cavity obtained no exudation, heart soft, flabby and
congested.
EXPERIMENT 15.--_Toxic and irritant action of chlorlyptus when
injected into the pleural cavity._--Six normal guinea-pigs used for
the experiment. Chlorlyptus was injected in the pleural cavity as
follows: Guinea-Pig 1, 0.5 c.c.; Guinea-Pig 2, 1 c.c.; Guinea-Pig 3,
2 c.c.; Guinea-Pig 4, 3 c.c., and Guinea-Pig 5, 4 c.c. Guinea-Pig 6
was used as a control.
Result: Guinea-Pigs 1 and 2 recovered about four hours after
injection. Guinea-Pig 3 died three days after and Guinea-Pigs 4 and 5
four and two hours after, respectively.
Conclusions: Guinea-pigs weighing on the average of 400 gm. may be
injected peritoneally with one or two c.c. or intrapleurally with
0.5 to 1 c.c. of chlorlyptus without having fatal results from the
injection.
EXPERIMENT 16.--_Toxic and irritant action of eucalyptus oil._--Three
normal guinea-pigs were used for the experiment. Guinea-Pig 1 was
injected with 1 c.c. of oil of eucalyptus in the peritoneum, and
Guinea-Pig 2 with 0.5 c.c. in the pleural cavity. Guinea-Pig 3 was
used as a control.
Result: Guinea-Pig 1 died about three hours after injection, and
Guinea-Pig 2 about two hours after the injection.
Autopsy: Both guinea-pigs showed marked congestion and a moderate
degree of exudate in the peritoneum.
EXPERIMENT 17.--_Toxic and virulent action of eucalyptus._--Three
normal guinea-pigs were selected for the experiment, as in Experiment
16. The injection was made in the pleural cavity. Guinea-Pig 1 was
injected with 0.5 c.c. and Guinea-Pig 2 with 1 c.c. of eucalyptus oil.
Result: Guinea-Pig 1 died the following day, and Guinea-Pig 2 one
hour after the injection.
EXPERIMENT 18.--_Toxic and irritant action of dichloramin-T, 0.5 per
cent. in chlorcozane._--One guinea-pig was used for each experiment.
Guinea-Pig 1 was injected with 0.5 c.c. and Guinea-Pig 2 with 1 c.c.
of dichloramin-T peritoneally.
Result: Both animals became restless immediately after the injection,
and died twelve hours after of acute hemorrhagic peritonitis.
EXPERIMENT 19.--_Effect of chlorlyptus on staphylococcus suspended in
salt solution and one of that solution injected into the peritoneum
of the guinea-pig._--Three guinea-pigs were used for the experiment.
Guinea-Pig 1 was injected with 0.5 c.c. of staphylococcus suspension
as control. Guinea-Pig 2 was given the same, and immediately after
received 1 c.c. of chlorlyptus. Guinea-Pig 3 was injected with the
same amount, and chlorlyptus was injected twenty-four hours after
injection.
Results: Guinea-Pig 1 was sick and weak with loss of appetite for
some days, but gradually recovered. Guinea-Pig 2 died over night.
Autopsy: There was a large amount of exudate in the peritoneal
cavity, irritation of the intestine, and other signs of acute
inflammation. A moderate degree of congestion; spleen not enlarged;
liver showed cloudy swelling and fibrinous exudate; lungs and heart
about normal except for a moderate degree of congestion but no
exudate. Guinea-Pig 3 was sick for some days, but recovered gradually
one week after.
EXPERIMENT 20.--_Effect of chlorlyptus in vivo on
staphylococcus._--The experiment was conducted in the same way as in
Experiment 17, but 2 c.c. were used instead of 1 c.c.
Result: Guinea-Pig 1 was injected with 2 c.c. staphylococcus
suspension and died over night. Autopsy showed that the animal died
of acute peritonitis. The peritoneum showed some fibrinous exudate
and mesenteric vessels. Guinea-Pig 2 was injected with 2 c.c. of
staphylococcus, and eighteen hours after was injected with 1 c.c. of
chlorlyptus. The animal died two weeks after injection. Guinea-Pig 3
was injected with 2 c.c. staphylococcus suspension, and twenty-four
hours after with 1 c.c. of chlorlyptus. The Guinea-Pig died ten days
after. Autopsy revealed bronchopneumonia of the left lung and acute
miliary abscess in the liver.
--(_From The Journal A. M. A., Nov. 27, 1920, with additions._)
AQUAZONE (OXYGEN WATER)
Report of the Council on Pharmacy and Chemistry
Aquazone is stated by the Aquazone Laboratories, Inc., Los Angeles,
California, to be a supersaturated solution of oxygen in water,
carrying approximately five and one-half times as much dissolved oxygen
as ordinary water. In an advertising booklet, it is suggested that
Aquazone is of value in the treatment of influenza, pneumonia, typhoid,
Bright’s disease and kindred disorders. It was also stated therein
that in the treatment of fevers it lowers the temperature, and that
the administration of three bottles of Aquazone (representing 0.033
gm.--1-1/2 grain--of oxygen) is of value for “preventive and tonic
purposes.”
The evidence which the Aquazone Laboratories submitted did not show
that the effects were other than those which might be obtained from the
administration of ordinary potable water. The Council declared Aquazone
inadmissible to New and Nonofficial Remedies, because the therapeutic
claims made for it were unwarranted, and because its use is irrational
for the reason that oxygen given by stomach in this way is of little
or no value.--(_Abstracted from Reports of Council on Pharmacy and
Chemistry, 1920, p. 50._)
COAGULEN-CIBA OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
announcing the deletion of Coagulen-Ciba from New and Nonofficial
Remedies.
W. A. Puckner, Secretary.
Coagulen-Ciba, a product of the Society of Chemical Industry, Basle,
Switzerland, was admitted to New and Nonofficial Remedies in 1915.
It is stated to be an extract prepared from blood platelets and to
contain thromboplastic substances (cytozym, thrombokinase, thrombozym)
mixed with lactose. Extensive clinical reports appeared to justify its
acceptance for New and Nonofficial Remedies with Fibrin Ferments and
Thromboplastic substances.
In 1918, Dr. Arthur D. Hirschfelder reported to the Council that of
a number of specimens of Coagulen-Ciba examined by him, failed to
accelerate the coagulation time of blood.
In view of Dr. Hirschfelder’s findings, the Therapeutic Research
Committee of the Council invited Dr. P. J. Hanzlik to undertake an
exhaustive investigation of thromboplastic substances, the Council,
in the meantime temporarily retaining Coagulen in New and Nonofficial
Remedies until the investigation was completed.
The following report on the eligibility of Coagulen-Ciba was made to
the Council by Dr. Hanzlik:
_Object_: To test the claims of thromboplastic and hemostatic
activities.
_Claims_: Coagulen is alleged to be a “physiological styptic prepared
from the natural coagulants of animal food contained in the blood
platelets. It has the characteristics of a lipoid.” (If cephalin is
meant it is difficult to understand why platelets should be selected
in preference to other abundantly supplied organs such as brains).
“Coagulen is indicated in all cases of external and internal
hemorrhage due to a deficiency of the coagulating power of the blood:
epistaxis, hemophilia, hemorrhage from gastric or duodenal ulcer,
melaena neonatorum, hemorrhage from the gums, the lungs, the bladder,
the uterus, hemorrhage during or after operations (turbinectomy,
tonsillectomy). It has also been used as a prophylactic before
operations, likely to produce severe hemorrhage.”
“In cases of true hemophilia one application of 5 grains of coagulen
usually suffices to control the hemorrhage.” “In gastric and
intestinal hemorrhage the internal administration of coagulen will be
found effective.” “In bonegrafting, plastic surgery, dentistry and
nose and throat surgery the application of a 10 per cent. solution of
Coagulen will be found to be of valuable assistance in controlling
hemorrhage and oozing.”
“It is a non-toxic and non-irritating powder to which a certain
amount of sugar has been added, with a view to ensuring its prompt
solution in water or physiological sodium chloride solution.”
_Description_: “Coagulen is a yellowish granular powder with but
slight odor, a sweet taste and is readily soluble in water or a
normal salt solution.” The dry Coagulen obtained corresponds to
the description claimed. Old specimens show the presence of dark
brown particles. Coagulen is marketed in 3 forms: (1) as dry powder
containing lactose, which, it is claimed, facilitates solution in
water; (2) as 3 per cent. sterile solution in ampoules;[137] (3)
tablets.
[137] An ampoule labeled as follows: “Coagulen-Ciba, 20 c.c. in
sterile solution ready for use. To be shaken. Importé de Suisse. Op.
No. 968” was found to measure only 15 c.c. Another ampoule with the
same label and Op. No. 9641 contained considerable sediment.
_Methods of Study_: The alleged thromboplastic activity was tested by
the method of Howell and a modification of this method by Fenger as
described in “New and Nonofficial Remedies.” In the Howell method dog
or cat blood is used, while beef blood at body temperature is used in
Fenger’s method. In other respects the methods are essentially the
same. Briefly these consist of noting the acceleration of coagulation
time in a mixture of equal parts of serum and the thromboplastic
agent to which about an equal part of oxalate plasma is added. Under
these conditions cephalin causes clotting in about 1 minute or even
less as compared with 20 to 30 minutes or more of the control.
The effects were compared with freshly prepared cephalin and other
thromboplastic agents, using saline (0.9 per cent. NaCl) as control.
The effect of different concentrations was also studied.
The literature of the manufacturers claims that Coagulen is harmless.
This was tested by making intravenous and subcutaneous injections
into guinea-pigs, using saline and cephalin as controls.
Bloods of 4 different species were used, namely, cat, dog, beef and
human. Dog’s peptonized blood and plasma were also tried.
The 15 different tests that were made in vitro were carried out with
3 different samples of fresh dry Coagulen (from manufacturer), 2
old samples (one from Council on Pharmacy and Chemistry and one of
our own), 3 fresh specimens of sterile solution in ampoules (from
manufacturer), one old specimen and 4 small ampoules (Council on
Pharmacy and Chemistry).
The tablets were not tested since these are made from dry Coagulen
and the results would hardly be expected to show anything different.
_Results_: The results obtained may be briefly summarized as follows:
(1) 0.1 per cent. to 5 per cent. Coagulen did not accelerate the
coagulation time of blood and oxalate plasmas in the majority of
tests any more than the controls of saline, while 0.1 per cent.
cephalin was found to shorten the coagulation time from 1/3 to 1/2.
(2) There was no difference between the behavior of old and fresh
specimens.
(3) No acceleration of coagulation _in vitro_ was observed even with
the highest concentrations tried, namely 25 and 50 per cent.
(4) Irrigations made with fresh dry coagulen in solution and sterile
solution in ampoules on superficial bleeding from the foot-pads of 3
normal and peptonized dogs and local application to hemorrhages from
dissected femoral arteries and bone and liver wounds of 3 dogs showed
that coagulen was no more active than normal saline.
_Toxicity_: Subcutaneous and intravenous injections of different
doses of Coagulen solutions (fresh ampoules) and dry Coagulen
in solution in 8 guinea-pigs produced definite anaphylactoid
symptoms with injury to the circulatory and respiratory systems as
indicated by cardiac dilatation, abdominal congestion and pulmonary
hemorrhages, congestion, distention and sometimes thrombi. On the
other hand, the control animals injected with saline and cephalin
remained practically unharmed.
_Conclusions_: The results obtained justify the following conclusions:
(1) Coagulen is entirely inactive as a thromboplastic and hemostatic
agent.
(2) Coagulen is distinctly injurious when injected systemically.
(3) The claims of hemostatic efficiency and harmlessness for Coagulen
by the manufacturer appear exaggerated and unjustified.
_Recommendations_: Because of its uncertain composition, the
possible dangers when injected systemically, and its inactivity as a
thromboplastic and hemostatic agent when tested by several different
methods, Coagulen merits no recognition as a therapeutic agent for
inclusion in New and Nonofficial Remedies.
The detail evidences used as the basis of this brief report
concerning Coagulen will be published shortly in the _Journal
of Pharmacology_,[138] together with the results with other
thromboplastic agents.
[138] Since the report was sent to the manufacturers, the results
have been published. Hanzlik, P. J., and Weidenthal, C. M., Plasma
and Blood Clotting Efficiency of Thromboplastic Agents in Vitro and
their Stability, J. Pharmacol. and Exper. Therap. =14=:157 (October)
1919; Hanzlik, P. J., Karsner, H. T., and Fetterman, J., Anaphylactoid
Conditions, J. Pharmacol. and Exper. Therap. =14=:189 (Oct.) 1919;
Hanzlik, P. J., Karsner, H. T., and Fetterman, F., Anaphylactoid
Phenomena from Thromboplastic Agents, J. Pharmacol. and Exper. Therap.
=14=:229 (Nov.) 1919.
The preceding report was sent to the American agent for the Society of
Chemical Industry, Sept. 8, 1919.
In reply the American agent, Ciba Co., Inc., on March 22, 1920,
sent the Council “some additional clinical reports on the use of
Coagulen-Ciba in the treatment of Hemorrhages supporting our claims of
the merits of Coagulen-Ciba.”
The material submitted by the Ciba Co., contains no objective evidence
for or against the efficiency of Coagulen-Ciba but merely opinions. As
a rule these opinions are favorable though conditional and hedging and
quite unconvincing. Nothing was submitted to offset or challenge the
findings of Dr. Hanzlik’s report.
Since the evidence indicates that Coagulen-Ciba has little, if any,
efficacy as a hemostatic, the Council directed its omission from New
and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and
Chemistry, 1920, p. 53._)
FERRIC CACODYLATE OMITTED FROM NEW AND NONOFFICIAL REMEDIES
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the report which appears
below, explaining the omission of ferric cacodylate from New and
Nonofficial Remedies.
W. A. Puckner, Secretary.
Iron cacodylate, the ferric salt of cacodylic acid, was admitted to New
and Nonofficial Remedies in 1917. It is required to contain from 39.7
to 44.9 per cent. of arsenic (As).
The following statement of the action, uses and dosage of iron
cacodylate appears in the 1920 edition of New and Nonofficial Remedies:
“Actions and Uses.--Ferric Cacodylate has the properties of iron
salts and of arsenic. Its use has been proposed in conditions
in which the effects of iron and the mild arsenic action of
cacodylates is desired.
“Dosage.--from 0.015 to 0.1 Gm. (1/4 to 1-1/2 grains).”
The period for which the iron cacodylate preparations now in New and
Nonofficial Remedies were accepted coming to an end with the close of
1920, the Council decided to determine if sufficient evidence for the
value of ferric cacodylate has accumulated to warrant its continued
recognition. The following is the report of the referee of the
Committee on Therapeutics to whom the matter was assigned:
“As far as the Referee knows, the only claim that Iron Cacodylate has
as a therapeutic agent is that it forms a convenient method for the
administration of Iron and Cacodylate (while there is no reason why
a drug should not be given by mouth, usually intramuscularly, and
apparently it has recently been given intravenously). The effects to
be expected from its use are those of iron and arsenic.
“Granted that iron and arsenic are valuable therapeutic agents, Iron
Cacodylate is not a satisfactory preparation in which to administer
these drugs for the following reasons:
“1. It would appear that Cacodylates are not the best form in which
to administer arsenic. Cacodylates in therapeutic doses exert but a
feeble action. Small quantities may be reduced to cacodyl (CH₂)₄As₂,
and varying amounts to inorganic arsenic. The amount transformed
to arsenic is apparently unknown and probably varies in different
individuals. On these grounds alone the use of the cacodylates where
an arsenic effect is desired seems dubious.
“2. The amounts of iron and cacodylates contained in the doses
recommended are small when compared with the usual doses of either
iron or cacodylate. The amount of iron in the Iron Cacodylate
preparations is small, about .0036 gram per dose, while the
preparations admitted to ‘Useful Drugs’ contain much larger amounts
per dose recommended. The list follows:
Massa Ferri Carbonates Fe per dose .042 gm.
Pilulae Ferri Carbonates " .058 gm.
Tinctura Ferri Chloride " .022 gm.
Ferri et Ammonii Citrae " .042 gm.
“The approximate amount of arsenic in Iron Cacodylate in the commonly
recommended doses varies from .012 gm. to 0.024 gm., while the amount
of arsenic in Sodium Cacodylate in the recommended doses varies
between .021 and .35 gms. It would seem that a much more rational
method of administration of these two drugs would be separately, in
which case a better control over the dosage is possible.
“3. The Referee has been unable to secure reliable clinical evidence
that Iron Cacodylate is a serviceable preparation. A search of the
available literature for the past fifteen years has been made, also
Drs. Edsall, Longcope, Stengel, Hoover, Phillips and Miller have been
consulted. These physicians know nothing of its use.
“4. In view of the above, it appears to the Referee that Iron
Cacodylate is an irrational and useless method of the administration
of iron and arsenic.”
The Council adopted the report of the referee and directed that iron
cacodylate be omitted from the 1921 edition of New and Nonofficial
Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1920,
p. 62._)
LIBRADOL
Report of the Council on Pharmacy and Chemistry
The Council has authorized for publication the following report which
explains why Libradol was found ineligible for New and Nonofficial
Remedies.
W. A. Puckner, Secretary.
Libradol is manufactured by Lloyd Bros., Cincinnati. According to a
circular (a “readily removable” label) which accompanies the trade
package, its “uses” are: “In colds, croup and acute bronchitis. In
local congestions; in lung trouble, in acute inflammations of this or
any other organ, especially if pain or soreness be present. In lumbago,
sciatica, or in rheumatic pains of the joints or muscles. Applied to
the forehead, it induces sleep.”
Libradol is offered in two forms, “Libradol Mild” for infants and
supersensitive persons which is said to be “destitute of drug energy”
and Libradol “Regular” which is “highly medicated,” the “constituents”
being “DRACONTIUM, SANGUINARIA, CEPHAELIS, MELALEUCA, LOBELIA, LAURUS,
CAPSICUM, TOBACCO.”
According to a circular, “The sanitary plasma Libradol” is a
“homogeneous, highly medicated, and exceedingly potent compound, in
plastic form,” which “carries the energies of its drug constituents
and the high antiseptic qualities of Laurus Camphora and Melaleuca.”
It is stated: “The Drug Influence of Libradol is necessarily different
from that of any known single member of the Materia Medica. But yet,
no mystery either in medicine or of pharmacy is claimed as a part of
its composition or process of manufacture. It is a thing peculiar to
itself, the result of the study of the drugs from which it is derived
and compounded. These drugs may be studied at leisure by whoever cares
to do so....”
The following information bearing on the composition of Libradol was
furnished by Lloyd Brothers in response to a request from the Council
to aid in the consideration of the preparation:
“‘Compound Lobelia Powder’ has been, since 1852, official in the
_American Dispensatory_, in the first edition of which (1852) its
formula is given, as follows:
“‘Take of Lobelia, in powder, twelve ounces; Bloodroot and Skunk
Cabbage, in powder, of each, six ounces; Ipecacuanha, eight ounces;
Capsicus, in powder, two ounces. Mix them.’
“This preparation came increasingly into demand with the Eclectic
profession, the principal use for which it was first employed (as
an emetic), being finally displaced by its local application in
bronchial pneumonia troubles, when sprinkled on a greased cloth and
applied to the chest.”
“In 1898, Dr. Finley Ellingwood petitioned Lloyd Brothers to
make for him, in plasma form, ready for application, a compound
carrying the ingredients of the old ‘Compound Lobelia Powder,’
strengthened by the addition of Melaleuca leucadendron, Laurus
camphora and Nicotiana tabacum. Experiments not very encouraging
in a pharmaceutical sense were made, and it was not until repeated
requests had been made that a product was at last satisfactorily
prepared and forwarded to Dr. Ellingwood (1900), with no thought
other than that of serving him personally in his practice. This
product he used and commended to his professional friends, and
under his commendation it came into professional demand.”
An examination of the information submitted by Lloyd Brothers showed
Libradol to be in conflict with the principles and rules that govern in
the acceptance of articles for New and Nonofficial Remedies as follows:
Composition (Rule 1).--The information which has been received
gives little idea of the actual composition of the preparation; for
example, the statement that Libradol “carries the energies of its drug
constituents and the high antiseptic qualities of Laurus Camphora
and Melaleuca” gives no indication as to the part or parts of the
Laurus Camphora or Melaleuca employed. If the statement is correct,
that Libradol “is a homogeneous, highly medicated, and exceedingly
potent compound,” it is essential that the several potent ingredients
be stated clearly and not merely hinted at by their qualities. Other
conflicts with Rule 1 might be enumerated, but the foregoing citations
state the direct conflict; and this has not been removed, although an
inquiry was sent to Lloyd Brothers for a statement of the amount of
each potent ingredient in a given quantity of Libradol.
Indirect Advertising (Rule 4).--The recommendation for the use of
Libradol in the treatment of colds, bronchitis, lumbago, sciatica and
rheumatic pains, which accompanies the trade package, is prone to
lead the public to depend on it in cases where definite treatment is
imperative.
Unwarranted Therapeutic Claims (Rule 6).--Libradol is recommended in
a great variety of conditions and is especially claimed not only to
relieve pain, but to remove the cause of pain. This is explained as
follows: “In the study of the physiological action of many drugs, it
was found that the constituent remedies in this combination exercised
a most salutary influence, not only upon the sensibility of the nerves
involved, but upon the capillary circulation within the diseased area,
the muscular structures therein included, and, subsequently, upon the
course of the advancement of the congestive and inflammatory processes,
and upon secretion, exudation, adhesion, induration, hypertrophy,
suppuration and excretion.”
Granting, for the sake of argument, that carefully controlled
experimental clinical evidence were available to substantiate this
statement with reference to a single case of pain, the statement
would be misleading when considered as a general explanation of the
preparation’s relieving pain by removing the cause of pain when taken
in connection with the conditions for which it is recommended and in
which pain is even a minor symptom. Still, if pain were relieved in
these cases by removing the cause, the patient would be cured of the
conditions which give rise to the pain, and these include: “Acute
pain in the chest;... acute inflammation in the chest;... persistent
local pain;...” (This might be interpreted as including tuberculosis;
pneumonia; cancer, and appendicitis.) “lumbago; sciatica; articular
rheumatism” (gonorrheal infections?).
Name (Rule 8).--The name, derived from _Dolar_ and _Liber_, suggests
the claimed action of the preparation (the relief of pain) rather than
the drugs said to be presented by it.
Irrational Composition (Rule 10).--It is quite possible that Libradol
will relieve pain in certain instances and that the drug constituents
present in Libradol “Regular” make this more effective than “Libradol
Mild” which is “destitute of drug energy”; this, however, is no
justification for the use by physicians of a cataplasm containing
or made from skunk cabbage, bloodroot, ipecac, melaleuca (oil of
cajeput?), lobelia, laurus comphora (camphor?), capsicum and tobacco.
The combination is thoroughly irrational and a reminder of a past
century. Further, the Council knows of no evidence to support the
following claims:
“As a stimulant Capsicum has the power of neutralizing depressant
remedies like Lobelia and Tobacco.”
“Our association of its desirable constituents with those of
Lobelia, in connection with the modifying influence of Capsicum,
Melaleuca, and Laurus Camphora, permits a more free use in Libradol
than would be possible were it to be employed alone.”
“Capsicum, Melaleuca, and Laurus Camphora in Libradol tend to
counteract the excessive relaxative and depressant effects of
Lobelia.”
“The great value of Melaleuca in Libradol is its quality of
modifying and controlling the action of the associated energetic
constituents of the drugs Tobacco and Lobelia, which reduce
congestion and inflammation, but which would, unsupported, be too
depressant.”
Libradol is inadmissible to New and Nonofficial Remedies because its
composition is complex, irrational and semi-secret, and because its
name and the unwarranted therapeutic recommendations made for it will
lead to its ill-advised use.--(_From Reports of Council on Pharmacy and
Chemistry, 1920, p. 65._)
HELMITOL OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Helmitol is hexamethylenamin methylencitrate. It was introduced with
the claim that it was superior to hexamethylenamin--which acts in acid
fluids only--in that it is equally efficient whether the urine is
alkaline or acid.
In 1918 The Bayer Company, which then marketed the product in the
United States, was notified that the Council questioned the claims made
for Helmitol and desired evidence to substantiate them. In 1919 the
same notification was sent the Winthrop Chemical Company, which in the
meantime had secured control of the product. Pending the submission
of the evidence, the Council continued the acceptance of Helmitol
for New and Nonofficial Remedies with the statement that the actions
and uses of hexamethylenamin anhydromethylencitrate were those of
hexamethylenamin.
W. A. Puckner, Secretary.
The following report on Helmitol was made by the referee in charge of
hexamethylenamin compounds and preparations, adopted by the Council and
sent the Winthrop Chemical Company:
“Helmitol is a compound of anhydromethylencitric acid and
hexamethylenamin. It was introduced with the claim that it would be
antiseptic even in alkaline urine. The Council did not entirely trust
the evidence, but continued to list Helmitol in N. N. R., merely as
a salt of hexamethylenamin, until satisfactory data should become
available. These have now been furnished by Hanzlik (_Journal of
Urology_ =4=:145) who has shown that:
“1. The alkalinity required to split off formaldehyd from
anhydromethylencitric acid is greater than exists in the urine, even in
advanced ammoniacal fermentation.
“2. Even if any formaldehyd were liberated in ammoniacal fermentation,
it would at once become inactive by combining with ammonia.
“3. Urine after the administration of anhydromethylencitric acid
actually putrefies readily.
“4. Less than 5 per cent. of the anhydromethylencitric radical reaches
the urine, the remainder being destroyed in the body.
“The only reason for the existence of Helmitol was this claim of
antiseptic action in alkaline and putrefying urines. Since this has
been disproved, there remains no reason for retaining Helmitol in
N. N. R.; on the contrary, its retention would only tend to continue
the fallacy on which it is based.
“It is, therefore, recommended that Helmitol be no longer listed with
New and Nonofficial Remedies, and that this report be published, after
the usual submission to the manufacturers.”
In accordance with the recommendation of the report, the Council has
directed the omission of Helmitol from New and Nonofficial Remedies
and has authorized the publication of this report.--(_From The Journal
A. M. A., Jan. 22, 1921._)
SPIROCIDE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
“Spirocide” (The Spirocide Corporation of New York) is advertised as a
new and successful treatment of syphilis by fumigation and inhalation.
According to the information presented to the Council, Spirocide is a
mechanical mixture of metallic mercury 25 per cent., copper sulphate 25
per cent., cypress cones 20 per cent., henna 20 per cent., nut gall 5
per cent., and dried pomegranate 5 per cent. It is supplied in the form
of greenish-gray tablets weighing about 10 gm. each, and containing,
therefore, about 2.5 gm. (about 38 grains) of mercury. It is sold in
packages of six tablets.
The following directions for its use are contained in a pamphlet
recently distributed:
“Spirocide is administered by means of fumigation and inhalation.
The patient is disrobed to the waist and placed in a light chair,
preferably with arms. A pastil or tablet of Spirocide is placed on
a small plate, or open receptacle, after being ignited by holding
in a gas or alcohol flame for a minute or so until it begins to
smoulder. The plate with the burning Spirocide is then placed on
the floor between the patient’s feet or just under the chair. A
small shelf or platform between the lower rounds of the chair is
an excellent location for the plate containing the burning mass.
When all is in position a sheet should be thrown over the patient
and arranged to enclose the whole. The patient should breathe
naturally and inhale the vapor, which will rise and fill the canopy
surrounding him. The treatment will require 15 to 30 minutes, or
until the Spirocide is burned up. The patient may complain at first
of a slight choking sensation, and there may be some tendency to
cough. This can be removed by raising the sheet long enough to
let in a little clear air. The eyes should be closed or lightly
bandaged to avoid smarting.”
Experiments conducted in the A. M. A. Chemical Laboratory show that
Spirocide, when ignited, burns slowly with consequent volatilization
of mercury. The several organic constituents serve as fuel and the
copper sulphate possibly acts as a regulator of the combustion. During
the burning process the cypress cones, henna, etc., are consumed but
most, if not all, the copper remains behind, the mercury only being
vaporized. It is asserted in the advertising pamphlet that Spirocide is
indicated in all stages of syphilis, primary, secondary and tertiary,
and in all its complications or sequelae. In these varying conditions
one tablet daily or every other day is recommended until six treatments
have been taken, though it is stated that “occasionally, depending on
the severity or the duration of the disease, it may be wise to give
nine treatments, the last three at intervals of two, three or more
days.”
Some of the results which it is claimed are obtained with Spirocide are:
“At the completion of this course of treatment with Spirocide,
all signs or evidences of syphilis are removed, and in ten days
to three months all Wassermann tests prove negative. Any further
treatments than the original course of fumigations are rarely
needed. Wassermann’s will be found uniformly negative after a
period which, according to the patient, may vary from ten days to
three months. These results have been obtained in cases in which
Salvarsan and kindred preparations have been employed without the
slightest benefit.”
In a letter to the Council the “scientific observer” of the Spirocide
Corporation declared:
“We do not claim that the vaporization method is new. We do claim,
however, that this combination of mercury produces more rapid
volatilization, certain absorption and undoubted effect than any
form of mercury administered by any method known to science without
the usual danger. That this is so we are willing to prove by
comparison with other methods both by ourselves and many observers
scattered over the United States....”
To determine the validity of the claims made for Spirocide, the
Corporation was asked to present the evidence which it offered. In
reply, the corporation’s “scientific observer,” Dr. J. Lewengood,
submitted 83 case reports from a number of different observers,
including those from military hospitals and a state institution, and
also a reprint of an article published by him in the _New York Medical
Journal_, Feb. 21, 1920, wherein were reported eight cases which
received “Spirocide Treatment.” In no case were controls with other
methods of mercury administration carried out.
This material the Council sent to two recognized syphilographers for
an opinion. One of the consultants reported that of the 83 cases,
20 dealt with patients who had also received arsphenamin medication
and, therefore, these 20 cases could not be considered as evidence
concerning the value of Spirocide. As to the remaining cases, he
found on the whole that the history and data furnished were far from
sufficient to warrant the claims made. In many of the cases emphasis
was laid on the Wassermann test, as though this test were the only
thing to be considered in a case of syphilis. He pointed out that in
one case the reaction changed from negative to strongly positive after
six treatments and that in several cases the phenomena reported cannot
be explained by anything else than a desire to get a negative blood
test. For example, one case had Spirocide treatment and a Wassermann,
1 plus, 55 days after; the author then reports that 19 days later the
reaction had become negative and, therefore, the change must be due to
Spirocide. In several of the cases reported it is even questionable
if the patients were syphilitic. The consultant concluded that the
evidence submitted by the Spirocide Corporation failed to prove the
claims made for Spirocide. He pointed out on the other hand that
patients readily become salivated from the use of Spirocide, often
after 8 or 10 treatments.
The second consultant replied that in his opinion the claim that
Spirocide produces more “undoubted effect than any form of mercury
administered by any method known to science without the usual danger,”
was not substantiated. He believed that it was not as effective as some
other methods, that the dosage is not as exact, and, therefore, it is
not as free from danger when the drug is pushed.
The Council’s two consultants were also asked whether or not, in their
opinion, the administration of mercury by inhalation is a method which
the Council should endorse to the extent of recognizing a preparation
based on this principle. This inquiry was also sent to the members of
the editorial board of the _Archives of Dermatology and Syphilology_.
Five replies were received. One advised a thorough study of the
different methods of administering mercury by inhalation. The other
four were opposed to such recognition on the ground that as the dosage
is not exact the effects, therefore, are not certain.
In consideration of the opinions expressed by its consultants, the
Council declared Spirocide inadmissible to New and Nonofficial Remedies
because (1) the claims made for it are unproved and unwarranted, (2)
the routine use of an inexact method for the administration of mercury
is detrimental to sound therapy and (3) the name is not descriptive of
its composition, thus failing to remind the physician who uses these
pastils that he is administering metallic mercury.--(_From The Journal
A. M. A., Jan. 22, 1921._)
DIGIFOLIN-CIBA NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized the publication of the following report,
declaring Digifolin-Ciba inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Digifolin-Ciba is a product of the Society of Chemical Industry
of Basle, Switzerland. It is marketed in the United States by the
Ciba Company, 91 Barclay Street, New York City. It is claimed that
Digifolin-Ciba is “a preparation of digitalis leaves that has been
freed from the useless and harmful principles such as Digitonin
(saponin), coloring and inert matter, etc., but does contain all the
really valuable, therapeutically active constituents of the leaves,
namely: digitoxin and digitalein in their natural proportions.” There
is no evidence that digifolin contains all of the glucosides of
digitalis as they exist in the leaf, and it is extremely improbable
that this is the case because one cannot remove saponin without
altering the other active principles of digitalis.
The Ciba Company sends out the following pamphlets relating to
Digifolin:
“‘Concerning Digifolin-Ciba, A New Preparation of Digitalis,’ by C.
Hartung, M.D., Ph.D. Extracts from the work ‘Ueber Digifolin, Ein
Neues Digitalis-Praeparat’ in the _Munich Medical Weekly_, No. 36,
page 1944, 1912.”
“‘Digitoxin Contents of Digifolin-Ciba,’ by C. Hartung, M.D.,
Ph.D., Basle, Switzerland. Reprints from the _Pharmaceutical Post_,
1913. No. 34, page 357. No. 40, page 431.”
“‘Pharmacological Tests of Digitalis,’ by M. J. Chevalier, Chef Des
Travaux Pratiques de Pharmacologie et Matiere Medicale, Faculte De
Medecine De Paris. Report Presented to the Societe de Therapeutique
at Their Meeting, May 28, 1913.”
In the reprint “Concerning Digifolin, ‘Ciba.’” Hartung lays stress
on the presence of harmful and inert substances present in the leaf
and galenical preparations with the direct or implied statement that
digifolin has an advantage in that these are absent from it. This is
misleading. It is true that Boehm whom Hartung cites, found saponin to
be irritating, but Boehm states that it required 100 mg. per kilogram
of body weight to induce vomiting after its oral administration.
Furthermore, saponin is present in traces only in infusion of
digitalis, so that the therapeutic dose contains a wholly negligible
amount of it.
The following occurs in “Pharmacological Tests of Digitalis,” by M. J.
Chevalier:
“Hartung’s Digifolin merits our attention, especially because
it seems to possess all the pharmacodynamic properties of
galenic preparations of digitalis without showing any of their
disadvantages.”
This claim scarcely needs comment, since it is well established that
the chief “disadvantages” of digitalis are inherent in the principles
which produce the desired effects of digitalis and may be avoided
to a large extent by a carefully regulated dosage of any digitalis
preparation. In short, the advertising for Digifolin asserts that this
digitalis preparation has all the advantages of digitalis itself, but
none of its disadvantages. This claim has been refuted so frequently
that manufacturers must be aware that it is untenable. Further the
claims now made for Digifolin are essentially those made nearly four
years ago at which time the attention of the American agent was called
to their unwarranted character.
The Council declared Digifolin-Ciba inadmissible to New and Nonofficial
Remedies because the therapeutic claims advanced for it are misleading
and unwarranted.--(_From The Journal A. M. A., April 2, 1921._)
SOME OF LOESER’S INTRAVENOUS SOLUTIONS
Report of the Council on Pharmacy and Chemistry
The Council has authorized the publication of the following report
on “Loeser’s Intravenous Solution of Hexamethylenamin,” “Loeser’s
Intravenous Solution of Hexamethylenamin and Sodium Iodid,” “Loeser’s
Intravenous Solution of Sodium Salicylate,” “Loeser’s Intravenous
Solution of Salicylate and Iodid,” “Loeser’s Intravenous Solution of
Sodium Iodid” and “Loeser’s Intravenous Solution of Mercury Bichlorid,”
put out by the New York Intravenous Laboratory, Inc.
W. A. Puckner, Secretary.
The intravenous solutions of “Hexamethylenamin,” “Hexamethylenamin
and Sodium Iodid,” “Sodium Salicylate,” “Sodium Salicylate and Sodium
Iodid,” “Sodium Iodid” and “Mercuric Chlorid” marketed by the New York
Intravenous Laboratory, Inc., are solutions of official substances sold
under their official names. They would, therefore, be outside the scope
of the Council, were it not that special and general therapeutic claims
are made for them. Such special claims, for instance, are contained in
an advertisement in the _Illinois Medical Journal_ for Oct. 20, 1920,
which gives, under the various drugs, a list of diseases in which the
drugs are said to be “indicated.” The Council is unable to agree with
some of these recommendations. The fundamental objection, however, is
the general claim of superiority and safety of the intravenous method.
The intravenous solutions named above would naturally have little sale
if such special claims were not made for them. While the claims may not
be made directly, they are carried by such display phrases as “For the
progressive physician seeking improved clinical results” and “A safe
practical office technique.”
The Council continues to hold that intravenous medication, generally,
is not as safe as oral medication even with relatively harmless
substances (a fact again illustrated by the results of Hanzlik and
Karsner, 1920, _Journal Pharmacology and Experimental Therapeutics_,
14, 379), and that it does not give “improved clinical results” except
under rather narrowly confined circumstances--namely, if the drug
undergoes decomposition in the alimentary tract, if it is not absorbed,
if it causes serious direct local reaction or if time is an urgent
element. Each intravenous preparation for which advantage over oral
administration is claimed, directly or by implication, must be examined
from these points of view.
The Council has recognized intravenous preparations which satisfied
these requirements. It is evident, however, that hexamethylenamin,
sodium iodid and sodium salicylate do not. When given orally they do
not undergo material decomposition in the digestive tract, they are
rapidly absorbed, they cause no direct local reaction, and in the
conditions in which they are used the hour or so which is required for
absorption is immaterial, especially as they are used continuously for
some time. Mercuric chlorid does indeed produce some local irritation,
but there is as yet no convincing evidence that its intravenous
injection causes less injury than oral administration. More experience
under controlled conditions is needed before the intravenous use of
mercuric chlorid can be approved. Especially objectionable are the
fixed proportion mixtures of sodium iodid with sodium salicylate and
with hexamethylenamin. The dosage of all three drugs has to be adapted
to individual conditions. This is impossible when giving them in fixed
proportions.
The Council voted not to accept “Loeser’s Intravenous Solution of
Hexamethylenamin,” “Loeser’s Intravenous Solution of Hexamethylenamin
and Sodium Iodid,” “Loeser’s Intravenous Solution of Sodium
Salicylate,” “Loeser’s Intravenous Solution of Salicylate and Iodid,”
“Loeser’s Intravenous Solution Sodium Iodid” and “Loeser’s Intravenous
Solution of Mercury Bichlorid” for New and Nonofficial Remedies because
they are sold under misleading claims regarding their alleged safety
and efficiency. In view of this fundamental objection the individual
claims for each preparation were not passed on.--(_From The Journal
A. M. A., April 16, 1921._)
“NATIONAL IODINE SOLUTION” NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
“National Iodine Solution” is a proprietary sold by the National Drug
Co., Philadelphia, Pa. From inquiries received by the Council on
Pharmacy and Chemistry it is evident that the product is extensively
brought to the attention of physicians by means of circulars. The name
implies that it is a solution of iodin and the inference is given that
it has the advantages of iodin without the disadvantages.
COMPOSITION
In view of the foregoing, the Council took up the investigation of
“National Iodine Solution,” and in turn asked the A. M. A. Chemical
Laboratory to analyze it. The chemist’s report follows:
According to the label of National Iodine Solution, “each fluidounce
represents three grains Proteo-albuminoid compound of iodin
(National)”; also an alcohol declaration of 7 per cent. is made.
Otherwise no information is given as to the composition either of the
“solution” or of “Proteo-albuminoid compound of Iodine.”
Each bottle contained about 115 c.c. (nearly 4 ounces) of a yellowish
solution, acid in reaction, having an odor resembling witch hazel; its
specific gravity at 25 C. was 0.9860. Qualitative tests indicated the
presence of zinc, alcohol, sulphate, an iodin compound (the solution
gave tests which indicated a very small amount of free iodin; most
of the iodin was in the form of ordinary iodid), a small amount of
vegetable extractives, and traces of aluminum and potassium. If any
protein was present, it was in amounts too small to be identified,
though a small amount of a nitrogenous compound was present. The amount
of solids in “National Iodine Solution” was equivalent to 0.72 per
cent, and the amount of ash, to 0.2 per cent. Quantitative estimations
yielded the following:
Alcohol (by volume) 7.0 per cent.
Zinc (Zn++) 0.096 per cent.
Iodin (free and combined) 0.029 per cent.
Sulphate (SO₄--) 0.146 per cent.
Protein (N × 6.36) 0.012 per cent.
The above findings indicate that each 100 c.c. contains about 7 c.c. of
alcohol, 0.5 gram of zinc sulphate U. S. P. (ZnSO₄+7H₂O.), 0.03 gram
of iodin, 0.01 gram of protein (calculated as such from nitrogen times
the factor 6.36) and some hamamelis water. Expressed in equivalent
apothecary terms, each fluidounce contains essentially:
Zinc sulphate 2-1/3 grains
Iodin (free and combined) 1/8 grain
Protein 1/25 grain
Alcohol 34 minims
This amount of alcohol is equivalent to about 3-1/2 fluidrams of witch
hazel water. Although the label states that each fluidounce contains
three grains of “proteo-albuminoid compound of iodine,” yet the sum of
the protein (calculated from nitrogen content) and iodin components is
equivalent to less than 1/5 grain.
“National Iodine Solution” appears to be very similar to “Gonocol” (The
National Drug Co., Philadelphia, Pa.), which was analyzed by the Bureau
of Chemistry of the U. S. Department of Agriculture. The bureau stated
that “it [Gonocol] consisted essentially of an aqueous solution of zinc
sulphate, hamamelis water, a small amount of alcohol, 0.38 grain of
iodin, and 0.36 grain of protein per fluidounce.”
It is evident that “National Iodine Solution” is not a solution of
free elementary iodin as the name suggests; instead it appears to be
a solution of zinc sulphate in witch hazel water containing less than
0.03 per cent. of combined iodin and _not more than a trace of free
iodin_. “National Iodine Solution” is one more to be added to that
already long list of proprietaries which makes capital of the high
esteem in which physicians hold iodin.
THE CLAIMS
An advertising circular sent to physicians begins:
“_Dear Doctor_: We beg to suggest a line of treatment while using
National Iodine Solution which our many years of experience has
proven to us to give the best and quickest results in the treatment
of inflammation of the urethral tract ...”
In it are given directions for the treatment of “acute gonorrhea,
male,” “anterior urethritis,” “anterior-posterior urethritis,” “ardor
urinæ and chordee,” etc., by means of National Iodine Solution and
other proprietaries of the National Drug Company’s make. In fact the
solution is claimed to be “Indicated in All Conditions of Urethra
Accompanied by a Discharge.”
COMMENT AND CONCLUSIONS
The therapeutic claims made for “National Iodine Solution” are
unwarranted. Such a solution is not indicated in all conditions of the
urethra accompanied by discharge. The advice contained in the circular
is equivalent to mail-order treatment of gonorrhea.
It is of interest to note that the claims for an identical or a
similar solution prepared by the National Drug Company as a treatment
for gonorrhea and intended for use by the laity, has been adjudged
misbranded by the federal authorities (Notice of Judgment No. 8150,
issued Jan. 25, 1921) in that it misled and deceived the purchaser
or purchasers thereof in the statements regarding the therapeutic
or curative effects of the article, which falsely and fraudulently
represent it to be indicated in all conditions of the urethra
accompanied with a discharge, “whereas in truth and in fact it was not.”
The Council would emphasize that if physicians give heed to advertising
such as that sent out by the National Drug Company for this preparation
the medical profession cannot with good grace protest against the
routine treatment of venereal diseases by quacks and “patent medicine”
venders.--(_From The Journal A. M. A., June 4, 1921._)
MON-ARSONE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report.
W. A. Puckner, Secretary.
Mon-Arsone is offered by the Harmer Laboratories Company as “a new
and non-toxic arsenical for the treatment of syphilis.” In the
advertisements for Mon-Arsone it has been claimed that with this
drug “the toxic, corrosive and uncertain reactions attending the use
of arsphenamine have been entirely eliminated” and that “it has a
therapeutic value equal to arsphenamine, but extensive case reports
fail to record the slightest toxic reaction following its use.”
According to the manufacturers, Mons-Arsone is disodiumethylarsonate,
the sodium salt of ethylarsonic acid, derived from arsenic acid by
replacement of one hydroxyl group by the ethyl group--AsO(CH₂CH₃)(OH)₂.
Mons-Arsone is related to sodium cacodylate, which is the sodium salt
of dimethyl-arsenic acid--AsO(CH₃)₂OH--derived from arsenic acid by
replacement of two hydroxyl groups by two methyl groups. Ethylarsonic
acid and its potassium salt were described by La Coste[139] more than
thirty-five years ago, and the use of the sodium salt of methylarsonic
acid was proposed in France some years ago. The Harmer Laboratories
Company claims originality for Mons-Arsone in that it was the first
to prepare the sodium salt of ethylarsonic acid and to propose its
therapeutic use.
[139] La Coste: Annalen der Chemie (Liebig’s) 208: 34.
It was reported several years ago by Castelli[140] that sodium
cacodylate and the sodium salt of methyl arsenic acid were devoid of
effect on experimental trypanosomiasis and spirochete infections.
Careful clinical observations in this country by H. J. Nichols[141] and
H. N. Cole[142] have demonstrated the inefficacy of sodium cacodylate
in the treatment of human syphilis.
[140] Castelli, G.: Arch. f. Schiffs- u. Tropen-Hyg. 16: 605, 1912.
[141] Nichols, H. J.: Salvarsan and Sodium Cacodylate, J. A. M. A. 56:
492 (Feb. 18) 1911.
[142] Cole, H. N.: A Study of Sodium Cacodylate in the Treatment of
Syphilis, J. A. M. A. 67: 2012 (Dec. 30) 1916.
Animal experiments carried out in the U. S. Hygienic Laboratory by
Voegtlin and Smith[143] show that Mon-Arsone is devoid of any practical
trypanocidal action. Thus the “therapeutic ratio” (the ratio of the
minimal effective dose to the lethal dose) was about 1, that is, it
was effective therapeutically only in approximately fatal doses; the
therapeutic ratio for arsphenamine in similar conditions was 17, and
that of neoarsphenamine, 28.
[143] Voegtlin, Carl, and Smith, H. W.: J. Pharmacol. and Exper.
Therap. 16: 449, 1921.
The findings that sodium dimethylarsenate (sodium cacodylate), sodium
methylarsenate, and sodium ethylarsenate are devoid of any practical
trypanocidal action and the conclusion that sodium cacodylate is
inefficient in the treatment of human syphilis does not prove
that Mon-Arsone is without effect on the disease. These findings,
however, certainly demand convincing therapeutic evidence to warrant
the recommendation for the use of the drug in the treatment of
syphilis--particularly because the drug is proposed as a substitute for
arsphenamine, the value of which is established.
When the Council first took up the consideration of Mon-Arsone, the
only evidence for the claim that it “has a therapeutic value at least
equal to that of arsphenamine” consisted, with one exception, of
reports from those who had experimented with the drug for the Harmer
Laboratories Company, including a report by B. L. Wright, L. A.
Kennell, and L. M. Hussey,[144] the latter of the Harmer Laboratories
Company. These reports appeared to show that the administration of
Mon-Arsone caused less reaction than arsphenamine, and that the
immediate effects, judged by clinical symptoms and the response to the
Wassermann test, appeared to be good. These trials extended over too
short a period of time to permit judgment as to the permanence of the
results. A report by an independent observer seemed to indicate that
Mon-Arsone does not have the sterilizing action on syphilitic lesions
which it is usually believed arsphenamine exercises.
[144] Wright, B. L.; Kennell, L. A., and Hussey, L. M.: M. Rec. 97: 607
(April 10) 1920.
After examining the available evidence, the Council advised the Harmer
Laboratories Company that the claim that Mon-Arsone has a therapeutic
value equal to arsphenamine appeared unwarranted; that, in the opinion
of the Council, Mon-Arsone should not be used except under conditions
that justify the experimental trial of an unproved drug, and should not
be used in a routine way until the permanence of its effects has been
established; and consequently any advertising propaganda for the drug
by the Harmer Laboratories Company was to be deprecated.
In its reply the Harmer Laboratories Company admitted that its
advertising claim, that Mon-Arsone was at least equal to arsphenamine
therapeutically, had been based on reports on fifty cases and on
additional reports that were beginning to come in at that time.
The Harmer Laboratories Company submitted a list of hospitals and
physicians using Mon-Arsone. A letter of inquiry sent by the Council to
those who, according to the names in the list supplied by the Harmer
Laboratories Company, had used Mon-Arsone, brought seven replies.
The clinical evidence contained in these replies was to the effect that
Mon-Arsone had been used in the various types of syphilis and that
there was a certain beneficial effect, both clinically and as shown by
the Wassermann reaction. In certain instances the Wassermann reaction
changed from a four plus to a negative reaction. The reports showed
that the efficiency of Mon-Arsone as compared with that of arsphenamine
preparations has not been adequately studied. One physician who has
used Mon-Arsone extensively reports that in many of the cases treated
there seemed to be nearly as good results from the use of Mon-Arsone as
is frequently obtained in the use of arsphenamine. He reports, however,
that it was necessary in eleven out of one hundred cases to change from
Mon-Arsone to neoarsphenamine.
In view of the fact that there is definite lack of evidence to show
that Mon-Arsone is the equal of arsphenamine therapeutically, and
because of the reports that in some cases it is inferior, Mon-Arsone
should not be used in the treatment of syphilis generally until its
therapeutic status has been more rigidly investigated and conclusive
evidence of its superiority to arsphenamine preparations obtained.
The Council voted not to admit Mon-Arsone to New and Nonofficial
Remedies and reaffirmed its conclusion that the claim that Mon-Arsone
has a therapeutic value equal to that of arsphenamine is premature and
unwarranted; that Mon-Arsone should not be used except under conditions
that justify the experimental trial of an unproved drug; and that the
advertising propaganda for the drug by the Harmer Laboratories Company
is to be deprecated.
* * * * *
When the preceding report was sent to the Harmer Laboratories Company,
the firm submitted a reply in which it was stated:
1. That in certain instances patients improved under Mon-Arsone who,
previously, had not improved under arsphenamine, and that this should
be taken to offset the report of the one hundred cases in which the use
of Mon-Arsone had to be abandoned in 11 per cent. of the cases.
2. That the Harmer Laboratories Company has abandoned the claim that
Mon-Arsone is therapeutically equal to arsphenamine and that it now
furnishes the drug to such men as care to use it simply on the basis of
its special and useful characteristics.
The Council heartily endorses the recent warning against the use
of untried medicaments which was issued by the U. S. Public Health
Service.[145]
[145] J. A. M. A. June 12, 1920, p. 1654.
Since the Council’s report was prepared a report on the effects of
Mon-Arsone on experimental syphilis has been published by Nichols,[146]
from the Division of Laboratories, Army Medical School, which concludes:
1. Disodium-ethylarsinate, or mon-arsone, tested on rabbits infected
with syphilis shows no spirocheticidal power. The tissues are fatally
poisoned as soon as or before the spirochetes are affected.
“2. For its practical use in syphilis there is no such germicidal basis
as exists in case of the arsphenamine group.”--(_From The Journal
A. M. A., June 18, 1921._)
[146] Nichols, H. J.: The Spirocheticidal Value of Disodium Ethyl
Arsenate (Mon-Arsone), J. A. M. A. 76: 1335 (May 14) 1921.
OXYL-IODIDE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
“Oxyl-Iodide” (Eli Lilly and Co.) is said to be the hydroiodid of
cinchophen and the claim is made that it exerts the effects of
cinchophen and of iodid. Because of inquiries which have been received
the Council decided to determine the eligibility of “Oxyl-Iodide” for
New and Nonofficial Remedies. Dr. P. J. Hanzlik--formerly Associate
Professor of Pharmacology at Western Reserve University School of
Medicine, now Professor of Pharmacology at Leland Stanford Junior
University Medical School--who has made a study of the action of
salicylates and cinchophen, was asked to report on the therapeutic
value and the rationality of “Oxyl-Iodide.” This he consented to do and
his report appears below.
After considering Doctor Hanzlik’s report, the Council declared
“Oxyl-Iodide” inadmissible to New and Nonofficial Remedies because it
is an irrational combination, marketed under claims that are unproved
and consequently unwarranted.
W. A. Puckner, Secretary.
“Oxyl-Iodide,” marketed by Eli Lilly & Co., is claimed to be the
hydroiodid of phenylcinchoninic acid, containing 33 per cent. of iodin
and 67 per cent. of phenylcinchoninic acid (cinchophen). Its solubility
resembles that of cinchophen, being low in water and acid mediums, and
higher in the presence of alkalis. Whether “oxyl-iodide” is decomposed
into its constituents in the presence of alkalis does not appear to
have been determined. However, if this were the case, the intestine,
after administration of “oxyl-iodide,” would contain cinchophen and
sodium iodid in the same forms as if these agents were administered
individually so that nothing would be gained by administering
“oxyl-iodide.” Being, like cinchophen, practically insoluble in acid
mediums, “oxyl-iodide” would have no advantage over the latter so far
as gastric irritation is concerned.
DOSAGE
The dosage advised is from one to three tablets containing 3 grains
(0.2 gm.) each of “oxyl-iodide.” The total dosage would depend on
the condition to be treated. In rheumatic fever, which requires a
full therapeutic or so-called, “toxic” dose of cinchophen, about 12
to 13 gm. would be administered intensively. Since each tablet of
“oxyl-iodide” contains 0.13 gm. of cinchophen, the total number of
tablets of “oxyl-iodide” required would be 100, or two and one-half
bottles of forty tablets each. At the same time the patient would
receive 6.6 gm. of iodin (as iodid). This might be distinctly
objectionable because of the production of the disagreeable symptoms of
iodism in some persons, and indicates that the fixed proportion of the
iodin constituent would be objectionable.
Even a smaller dosage, such as 5 gm. of cinchophen, which gives partial
relief in rheumatism and similar conditions, would still require a
patient to take a full bottle, or forty tablets, of “oxyl-iodide,” and
at the same time about 2.7 gm. of iodin would have to be ingested.
Furthermore, rheumatic fever, the arthritides, gout and related
conditions in which cinchophen is indicated do not require iodid.
Therefore, “oxyl-iodide” would not be the remedy of choice in these
conditions, and its use would be irrational and illogical.
ACTIONS
No data on the pharmacologic actions of “oxyl-iodide” are presented
in the manufacturer’s literature. Presumably, the compound would
exhibit the actions of its individual components, i. e., cinchophen and
iodin (as iodid), though probably less efficiently, owing to its low
solubility. This is also indicated by the following statements of the
manufacturer: “The analgesic action of ‘oxyl-iodide’ is gradual. A word
of caution is necessary to those who may expect immediate relief from
pain.” Therefore, why use “oxyl-iodide” in place of more dependable
analgesics, such as salicylate or cinchophen. The following statements
appear far-fetched: “There is a stimulation of the endocrines which
is perhaps more marked in the thyroid gland, although it is probably
shared by the pituitary and other glands which function in a chain-like
control.... There is stimulation of cells with increased flow of
secretion, visibly demonstrated by the nasal mucous membrane after
‘oxyl-iodide’ has been taken for some time. The general action on
mucous membranes favors elimination of toxins and waste products.”
It is probable that “oxyl-iodide” acts as a uric acid eliminant, though
there is no reason to suppose that it is more effective than cinchophen
alone. No data are given for this in the manufacturer’s literature.
USES
Successful use of “oxyl-iodide” is claimed in brachial and sciatic
neuritis, lumbago, muscular rheumatism, arthritis deformans, chronic
arthritis (“... in some instances were apparently cured”), subacute
bronchitis, circumflex neuritis, traumatic orchitis, eczema and
rheumatism. However, a careful reading of the protocols of seven cases,
representing these conditions, gives an unfavorable impression as to
the real contribution to the recovery by, or value received from,
“oxyl-iodide.” Summarized, the opinions as quoted by the manufacturers
in support of their claims for “oxyl-iodide” are briefly as follows:
Case 1. “Of course, the case is not complete yet, but I am looking for
continued betterment.”
Case 2. “For two weeks past her improvement has been marvelous.”
Case 3. “The joints are still enlarged and we do not hope to clear them
entirely....”
Case 4. “Undoubtedly, removal of the kidney had much to do with
improvement.”
Case 5. “I think I have gotten very good results.”
Case 6. “Some apparent benefit.”
Case 7. “She is practically free from pain, and the muscle and joint
stiffness is now slight.”
These inconclusive opinions certainly do not agree with the favorable
impression which other portions of the manufacturer’s literature
create. If the factor of natural recovery in the conditions represented
by these seven cases is given due weight, little, if anything, is
left to the credit of “oxyl-iodide.” Such clinical evidence as is
supplied by the manufacturer indicates that the therapeutic efficiency
of “oxyl-iodide” is doubtful, and not an improvement over either
cinchophen or iodid.
IODISM
Iodism cannot be avoided by the use of “oxyl-iodide,” for the
manufacturer’s literature states that “the dosage of ‘oxyl-iodide’
may be pushed to iodism as manifested by skin symptoms.... To avoid
iodism there should be an occasional interruption of treatment.”
“Oxyl-iodide,” therefore, has no advantage over ordinary sodium iodid
to avoid iodism. Usually, the conditions which require cinchophen
do not require the simultaneous administration of iodids, and vice
versa. If administration of iodid and cinchophen together should be
indicated or desirable, these can be given separately with the added
advantage that the iodid can be easily reduced or withdrawn in case
iodism supervenes, and the cinchophen could be continued if necessary.
Since conditions do not arise frequently enough to warrant the use
of iodid and cinchophen together, the existence of such a product as
“oxyl-iodide” is unwarranted.
Finally, the manufacturer himself recognizes that phenylcinchoninic
acid (cinchophen) can take the place of “oxyl-iodide.” Under
“dosage,” the circular states: “A few patients may be idiosyncratic
to the iodides and find they cannot take ‘oxyl-iodide.’ For the
latter chloroxyl, the hydrochloride of phenylcinchoninic acid, is
recommended.” The action of the hydrochlorid of phenylcinchoninic acid
does not differ, of course, from that of cinchophen. The difficulties
of assigning a clear-cut, definite, therapeutic rôle to “oxyl-iodide”
in order to justify its existence, alongside well-known and tried
remedies are self-evident.
CONCLUSION
“Oxyl-iodide” is pharmacologically and therapeutically an illogical,
irrational and unjustified substitute for cinchophen and iodids. The
conditions which require the administration of cinchophen do not as
a rule require the administration of iodid and vice versa. If it is
desirable to secure the effects of iodid and cinchophen together, these
can be more conveniently and advantageously administered as separate
agents, permitting in that way a better control of their actions. This
cannot be accomplished with “oxyl-iodide,” in which the proportion of
iodid and cinchophen are fixed. Symptoms of iodism cannot be avoided
by the administration of “oxyl-iodide.” The objective evidences for
its actions and uses are totally lacking; and the clinical opinions
concerning its therapeutic benefits in different disease conditions
are inconclusive and hedging, and, if anything, contradictory to the
favorable impressions which the language of the advertising matter is
likely to create.--(_From The Journal A. M. A., July 2, 1921._)
QUASSIA COMPOUND TABLETS
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report,
declaring that Quassia Compound Tablets (Flint, Eaton and Company) are
inadmissible to New and Nonofficial Remedies.
W. A. Puckner, Secretary.
Quassia Compound Tablets, marketed by Flint, Eaton and Company,
Decatur, Ill., according to the label on a trade package submitted to
the Council, contain in each tablet:
Quassia 3/4 grain Aloin 1/4 grain
Chionanthus 1 grain Ipecac 1/16 grain
Wahoo 3/4 grain Podophyllin 1/4 grain
Nux Vomica 1/2 grain Gingerine _q. s._
Cascara 1/3 grain
In the advertising the “Cascara” of the label is replaced by the
indefinite term “Cascarin” and the “Gingerine _q. s._” by “Carminative
Antigripe _q. s._” Flint, Eaton and Company informed the Council that
“Carminative Antigripe is C. P. Sodium Sulphite of which each tablet
contains 1/4 grain.” The tablets were treated with dilute hydrochloric
acid and the odor of sulphur dioxid became apparent. This shows that
the company’s statement to the Council, that the tablets contain a
sulphite, is correct and the formula on the label is incorrect.
In the advertising for this preparation we read:
“A careful study of this formula [which formula? That on the label
or that in the general advertising?--COUNCIL] will reveal the
outstanding fact that, while there are several drugs employed, each
ingredient is there for a purpose and all do splendid teamwork. If
your patient is constipated because the stomach is not sufficiently
energetic, the Quassia stimulates that organ to an increased
secretion of digestive fluids and sets it to working normally.
If the liver be sluggish, the Chionanthus and Wahoo prompt it to
increased activity. Chionanthus has no superior for producing a
sustained healthy hepatic condition. Should the bowels be slow
and uncertain, the small doses of Aloin, Cascarin and Podophyllin
stimulate to free peristaltic action, while the Nux Vomica sets the
nervous system right. We use an effective Antigripe so that there
is no griping.”
It is absurd to suppose that a complex mixture of drugs in fixed
proportions can have the actions claimed for Quassia Compound Tablets.
As regards the claim that “Chionanthus has no superior for producing a
sustained healthy hepatic condition,” it was brought out in a report
of the Council on “Some Unimportant Drugs” (Reports of Council on
Pharmacy and Chemistry, 1912, p. 36) that the “claims for this remedy
[Chionanthus] are not supported by experimental evidence and the
clinical reports of its use fail to show indications of discriminating
critical observation. It is not noticed by most pharmacologic
authorities.”
Of Wahoo (Euonymus N. F.) the “Epitome of the U. S. P. and N. F.”
says: “_Actions and Uses._--Obsolete cathartic; toxic digitalis
effects. _Caption_: the uncertain absorption of this drug makes its use
inadvisable.”
Quassia Compound Tablets (Flint, Eaton and Company) are inadmissible
to New and Nonofficial Remedies because (1) they contain drugs of
unproved value; (2) their composition is needlessly complex, and,
therefore irrational; (3) unwarranted therapeutic claims are made
for them; (4) the name is misleading and not descriptive of their
composition, and (5) the statement of their composition is indefinite
and incorrect.--(_From The Journal A. M. A., July 9, 1921._)
TOXICIDE
Report of the Council on Pharmacy and Chemistry
The Council has authorized the publication of the following report:
W. A. Puckner, Secretary.
Toxicide (Toxicide Laboratories, Chicago) is alleged to be a remedy
which “increases systemic resistance,” is “used for immunizing against
septic infections” and “is indicated in any case of septic infection,
capable of inducing inflammation and pus formation, regardless of
location or kind of tissue involved.” The following statements
bearing on the composition of the preparation are furnished by the
manufacturers:
“Toxicide contains Lachesis 12X, Tarantula 6X, Psorinum (special)
15X, Silicia 6X and Excipient q. s. (the excipient is sweet milk).
“These remedies are combined in the sweet milk and put through a
process of development, which produces the curative agent which we
call ‘Toxicide’ ...
“Put up in tablet form, sugar coated and colored red.”
No information is given as to the proportions, either relative or
actual, of the ingredients. Neither is any information given regarding
the “process of development” to which the mixture is subjected, nor the
amount of the finished mixture which is contained in Toxicide tablets.
The Toxicide Laboratories present the following “theory”:
“In combining these remedies and processing with milk, we develop a
latent immunizing active principle, which usually controls the most
virulently, active, septic infections promptly.”
[Illustration: Photographic reproduction (reduced) of an advertisement
of the “originator” of Toxicide; it ran for many months in the program
of a burlesque theater located in Ruckel’s neighborhood.]
There is no evidence, however, that any effort has been made to
demonstrate the presence of a “latent immunizing active principle” by
scientific methods of modern immunology. The following claims for the
use of Toxicide appear on the label:
“Acne, boils, carbuncles, furuncles and abscesses of the most
virulent types usually begin to show improvement within 4 to 12
hours after beginning administration.
“In badly infected wounds, Toxicide will check the further
destruction of live tissue and should always be given for a few
days before and after operations on pus cases.
“For gunshot wounds and other conditions difficult to sterilize or
drain, Toxicide is the ideal remedy.
“For abscesses existing or threatened in any obscure location, the
middle ear, the mastoid, the frontal or any accessory sinuses,
Toxicide is of inestimable value.
“If administered early, in fractures, compound or simple, or for
laceration and other injuries, inflammation, swelling, soreness and
destruction of tissue will be greatly mitigated.”
In support of these claims there are offered letters from physicians
who have used Toxicide with good results. None of these testimonials
present evidence that the reported effects were due to Toxicide.
The asserted--and highly improbable--action of Toxicide could be
determined only by an extensive series of carefully controlled clinical
trials--and such evidence is entirely lacking. In fact, the claims
appear to have no better basis than the coincidence which is stated to
have led to the discovery of the “remedy”; namely, that a boil on the
neck disappeared shortly after the administration of Toxicide!
The Council finds Toxicide inadmissible to New and Nonofficial Remedies
because (1) the identity and amount of the potent constituent or
constituents have not been furnished; (2) the preparation is advertised
indirectly to the public; (3) the name “Toxicide” is therapeutically
suggestive, and (4) the therapeutic claims, being unsubstantiated by
evidence, are unwarranted.
[Illustration: Photographic reproduction (greatly reduced) of an
advertising circular used some time ago describing the marvels
(alleged) of Toxicide.]
[Editorial Comment.--It seems rather preposterous that a scientific
body, such as the Council on Pharmacy and Chemistry, should have to
waste its time in investigating and reporting on such an obviously
unscientific product as “Toxicide.” So long, however, as there are
physicians who will take preparations of this sort seriously, the
Council feels that it is its duty to report on such products. The
problem, in fact, was well stated in a letter addressed to the
editor some months ago by the secretary of a county medical society
who had just received a visit from a representative of the Toxicide
Laboratories and who sent to The Journal some of the advertising matter
that he had received from the same source. This physician wrote:
“I do not wish to trouble you with this kind of material, usually
deposited safely in my waste paper basket, but the enclosed was handed
to me today by a ‘bird’ who is calling on all the doctors and making
strong statements. When he claimed that ‘Toxicide’ is being used in
the Presbyterian Hospital, Chicago, and that the Council on Pharmacy
and Chemistry is considering it seriously, etc., etc., I wish to know
whether I am missing any real good thing. If it has any real virtue,
I would like to know about it, but if it has not, it seems to me that
something ought to be done to head him off as some doctors are sure to
fall for some of it.”
The Toxicide Laboratories is, apparently, merely a trade name used by
the alleged originator of “Toxicide,” J. F. Ruckel, M.D. According to
our records, Ruckel was born in 1860 and was graduated by the Chicago
Homeopathic Medical College in 1886. He claims to have originated
Toxicide about twenty years ago and to have prescribed it “in over
3,000 cases.” In addition to Toxicide, the Toxicide Laboratories also
put out “Dianasiac for Nymphomania and Satyriasis” and “Somnosine for
Insomnia.”]--(_From The Journal A. M. A., Oct. 8, 1921._)
PIL. MIXED TREATMENT (CHICHESTER)
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report:
W. A. Puckner, Secretary.
“Pil. Mixed Treatment (Chichester)” is a proprietary preparation of
the Hillside Chemical Co., Newburgh, N. Y. It is sold in the form of
pills, each said to contain 1/20 grain of mercuric iodid and 5 grains
of potassium iodid.
In 1907 the Council examined the therapeutic claims advanced for this
preparation and found that they were unwarranted, exaggerated and
misleading. It found, also, many misleading statements in regard to the
product itself. Furthermore, the A. M. A. Chemical Laboratory found the
pills to be “short weight” in potassium iodid content.
At the time that the Council examined Pil. Mixed Treatment
(Chichester), a dermatologist of recognized standing, to whom the
“literature” for this product had been submitted for an opinion, made
the following report:
“Assuming that this pill contains what is claimed for it, one-twentieth
(1/20) of a grain of biniodid of mercury and five (5) grains of
potassium iodid, it presents neither an original nor a very useful
formula.
“The literature furnished by the company abounds in suggestions that
the mixture, as they prepare it, represents some unusual potency which
is not possessed by the ordinary mixture of these same drugs in the
same proportion. These suggestions may of course be dismissed without
consideration. There is nothing mysterious in a mixture of potassium
iodid and biniodid of mercury and this formula is no more entitled
to special consideration than any other pill or tablet of the same
composition prepared by any reputable pharmaceutical firm.
“The formula of this pill, however, does not represent a good
combination. It is offered for use both during the active secondary
period of syphilis and for tertiary lesions. The pill does not contain
enough mercury to be an efficient remedy for secondary syphilis and not
enough potassium iodid to be satisfactory in the treatment of tertiary
lesions. It is neither fish, flesh, fowl, nor good red herring. A
patient with secondary syphilis should not be dosed all the time with
potassium iodid and for the treatment of tertiary lesions he should
have a very much larger quantity of potassium iodid than can be given
in these pills without giving toxic doses of mercury.
“The statement that this pill ‘does not impair the appetite nor disturb
digestion and is well borne by patients who cannot tolerate iodids
otherwise administered’ is a bald claim which cannot be justified by
experience. The most unsatisfactory way of administering potassium
iodid is in solid form. A patient who can stand potassium iodid in pill
form, as it is furnished in this preparation, can stand it in any form
in which it is ever administered.
“In short this preparation is neither agreeable nor efficient. The
greatest objection to it is its inefficiency, for it is offered as
an adequate preparation for the treatment of syphilis in all of its
stages, whereas it is neither satisfactory for the treatment of
secondary syphilis nor of tertiary lesions.”
During the fourteen years which have elapsed since the Council’s first
examination of Pil. Mixed Treatment (Chichester), arsphenamin has
been added to the syphilographer’s armamentarium and much has been
learned about syphilis and its treatment. While there exist differences
of opinion as to the exact value of arsphenamin in the treatment of
syphilis and there are even some who desist from the use of arsenic
compounds of any kind, no syphilographer of standing countenances the
routine treatment of syphilis with a fixed combination of mercuric
iodid and potassium iodid. The use of Pil. Mixed Treatment (Chichester)
is on a par with the use of certain “blood purifiers” which were
advocated at a time when the treatment of syphilis was a baffling
problem.
PRESENT DAY CLAIMS
The present advertising, which reads as if it had been written in the
heyday of proprietary license, is, in effect, an invitation to treat
syphilis in its various stages and manifestations with Pil. Mixed
Treatment (Chichester). If heeded by those who read the advertising of
the Hillside Chemical Co., it will result in much harm to the public
and the profession. For this reason, the present report of the Council
is published as a protest against any advertising propaganda advocating
the routine treatment of a disease which requires that each case be
studied carefully so that prompt and efficient measures may be applied
to the various manifestations of the disease.
The following advertisement appeared recently in several medical
journals:
“Medicine is an Exact Science--on Paper Only!” Every general
practitioner of medicine is called upon to treat Syphilis
occasionally. He cannot depend upon the use of arsenicals alone.
In most cases, “mixed treatment” the giving of mercury and iodides
is required to get satisfactory results. PIL. MIXED TREATMENT
(CHICHESTER) accurately and successfully meets the indications and
assures definite action. Important advantages:
Ready solubility of mercury in combination with Potassium Iodide.
Avoidance of gastric, buccal or intestinal disturbance.
Easy administration, can be taken at any time, anywhere.
Economical, both drugs in one combination.
Accurate adjustment of dosage to each individual case.
Full physiological action--assured by purity of content.
Secrecy--patient or friends do not know nature of medicine. Pil
Mixed Treatment (Chichester) has been time tested and trial proven.
It needs no introduction to the thousands of physicians who
prescribe or dispense it.
While the advertisement does not directly so advise, yet it is a
subtle invitation to the general practitioner to use Pil. Mixed
Treatment (Chichester) and thus save himself and his patient the time
and inconvenience which the rational treatment of syphilis imposes. A
circular “The Treatment of Syphilis Simplified and Improved” begins:
“No therapeutic fact is more conspicuously and decisively
established than that a radical cure of syphilis can be effected by
the continuous administration, from the period of development, of a
proper combination of mercury with iodine.”
Continuing, it is admitted that mercury is the most efficacious drug in
the primary and secondary stages of syphilis and iodin in the tertiary
stage, but it is asserted that:
“... it is now granted by all syphilologists that the antiluetic
action of these drugs is immeasurably augmented by properly
combining them, and that the best results are obtained when they
are conjunctively administered throughout the entire course of the
disease.”
Arguing along the same lines, this circular continues:
“... it was not until mercury and iodine in the form of Pil. Mixed
Treatment (Chichester) was evolved that the marked advantages of
the combined employment of these drugs in the various stages of
syphilis became a scientific certainty.”
Further we are asked to believe that:
“Because of the greatly increased potency of mercury and iodine
when combined, as in Pil. Mixed Treatment (Chichester), the
foremost syphilologists are now agreed that the employment of
these drugs in such form should be enjoined as soon as the disease
develops, and should be thus continued until a cure has been
effected; in other words, Pil. Mixed Treatment (Chichester) should
be made the sole antisyphilitic medication throughout all stages of
the disease.”
The circular illustrates the extent to which our knowledge of drugs may
be distorted and misrepresented and the public health jeopardized in
the exploitation of a proprietary medicine.
[Illustration: One reason scientific medicine lags. Uncritical medical
journals perpetuate--for a price--the use of nostrums.]
PROPRIETARY CLAIMS
In its advertising, the Hillside Chemical Co. claims that Pil.
Mixed Treatment (Chichester) both as to formula and method of
preparation “in the incapsulated powder form” was “brought to the
notice of the profession by Dr. W. R. Chichester of New York, an
eminent Syphilographer and recognized authority in the therapeutics
of Syphilis.” It is claimed that this pill “is perfectly soluble,
tasteless, nonirritant, and therefore well adapted to a sensitive
stomach.” It is claimed that the pill “is always preferable to one
extemporaneously prepared, which, even if identical in composition,
often gives negative results.”
An examination made in the chemical laboratory of the association to
determine if the product now marketed contains the claimed amount of
potassium iodid indicated that this was the case. The chemist who made
this examination commented as follows on the claim that in this pill,
potassium iodid is rendered tasteless, that the pill is “perfectly
soluble” and that extemporaneous pills of “identical ... composition
often give negative results.”
“That the potassium iodid has been rendered tasteless is false,
naturally; the pills when placed in the mouth, after removal of the
coating, have the characteristic taste of alkali iodids. The claim
that the pills are entirely soluble is incorrect; they contain a large
amount of insoluble material, probably kaolin. The assertion that an
extemporaneous compound prescription even if identical in composition
with the Chichester pill is often inert, is absurd and a reprehensible
attack by suggestion of the ideal that the physician shall write his
prescription to meet the individual needs of his patient and that the
pharmacist shall compound the prescriptions of the physician as they
are required. It should also be pointed out that while much is said
about the potassium iodid in the Chichester pill being in powdered
form, the pill mass is solid and very slowly soluble and the claim of
being in powdered form is, if immaterial, also incorrect.”
As to the asserted standing of the alleged discoverer of the formula
for Pil. Mixed Treatment: Dr. William R. Chichester appears to have
lived and practiced in New York since 1886 or longer, but the claim
that he is an “eminent syphilographer” seems to have originated with
the exploiters of “Pil. Mixed Treatment.” Search failed to show the
name of W. R. Chichester among authors of textbooks of syphilis or any
other branch of medicine or among authors of contemporary literature in
the _Index Medicus_ from 1907 down to the present; nor did a search of
the catalogue to the Surgeon-General’s Library reveal W. R. Chichester
as ever having published anything on syphilis or any other subject.
Pil. Mixed Treatment (Chichester) is sold under therapeutic claims
which are unwarranted and misleading. The preparation well illustrates
the abuses which are connected with the exploitation as proprietaries
of established drugs or mixtures of established drugs.--(_From The
Journal A. M. A., Oct. 22, 1921._)
ATOPHAN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
explaining why Atophan has been omitted from New and Nonofficial
Remedies. Schering and Glatz, Inc., the firm which markets this
brand of cinchophen in the United States, has refused to place
either the U. S. Pharmacopeial name, “Phenylcinchoninic Acid (Acidum
Phenylcinchoninicum)” or the N. N. R. name, “Cinchophen,” on the label
and in the advertising matter so as to make the identity of the product
clear to physicians. Furthermore, the product is sold under therapeutic
claims which the Council holds to be exaggerated and unwarranted.
W. A. Puckner, Secretary.
COMMERCIAL HISTORY OF CINCHOPHEN
The substance, 2-phenyl-quinolin-4-carboxylic acid, was described by
Doebner and Gieseke in 1887 (_Ann. d. Chem._ [Liebig’s] =242=:291). The
therapeutic properties of this compound were described by Nicolaier and
Dohrn in 1908 (_Deutsch. Arch. f. klin. Med._ =93=:331). Subsequently
the product was placed on the market and extensively advertised by the
Chemische Fabrik auf Actien (vorm. E. Schering), Berlin, Germany. This
firm also took out a patent in the United States on its production
and in 1911 secured a U. S. trademark on the name “Atophan.” In
1912 Atophan was passed on by the Council and admitted to New and
Nonofficial Remedies.
When the government of the United States took charge of German-owned
patents during the World War, the Federal Trade Commission, and
later the Chemical Foundation, Inc., issued licenses to American
firms whereby these were authorized to manufacture the compound.
In the meantime, Schering and Glatz, Inc., who had been the U. S.
representatives for the Chemische Fabrik auf Actien, also undertook to
supply the drug, but did not obtain a license from the boards in charge
of German patents. Also, this firm secured, in 1919, a trademark of the
word “Atophan,” apparently after the German-owned trademark had been
canceled.
The drug “Atophan” was admitted to the U. S. Pharmacopeia as
“Phenylcinchoninic Acid (Acidum Phenylcinchoninicum).” As this name
proved too cumbersome, the Council on Pharmacy and Chemistry coined the
abbreviated name “Cinchophen” for it, and this name is now used by all
the firms which are marketing the product in the United States, with
the exception of Schering and Glatz, Inc., who use the term “Atophan,”
first owned by the Chemische Fabrik auf Actien.
ATOPHAN, A BRAND OF CINCHOPHEN
Because of the confusion which is bound to arise from giving various
names to one drug, the Council selects a common name and provides
standards of identity, purity and strength for any drug which, by
reason of the absence or lapse of patent rights or for other reason,
is open to manufacture by more than one firm. The Council, then, will
accept such article only if it is marketed under the title adopted
for New and Nonofficial Remedies. The rules provide, however, that
when the Council adopts a common name for an article that has been
admitted under another name, such article will be retained in New and
Nonofficial Remedies under the older name if the Council name is given
prominence on the label and in the circulars and advertisements, in
order to avoid confusion. Accordingly, when the period of acceptance
for Atophan in New and Nonofficial Remedies was about to expire,
Schering and Glatz were notified that Atophan could be retained in
that publication only on condition that the name, “Cinchophen,”
or else the pharmacopeial name, “Phenylcinchoninic Acid (Acidum
Phenylcinchoninicum)” be placed on the label and used in the circulars
and advertising.
UNWARRANTED THERAPEUTIC CLAIMS FOR ATOPHAN
At the time that the Council asked Schering and Glatz to adopt
cinchophen or phenylcinchoninic acid as a synonym for Atophan, the
firm was also requested to omit from future advertising a number of
therapeutic claims to which the Council was obliged to take exception.
Schering and Glatz refused the first request and made no definite
promise with regard to the second. The Council, therefore, directed the
omission of Atophan from New and Nonofficial Remedies, 1921.
The advertising to which the Council took exception does not appear to
be distributed at present. A pamphlet has been sent out, however, which
is equally objectionable. It contains unwarranted therapeutic claims
and suggests that Atophan be used in conditions in which it is not
indicated. For instance:
“No longer the vague, hypothetical, ‘test-tube demonstrated’
principle of uric acid elimination by solution, but a definite,
scientifically and clinically established, physiologic stimulation
of the uric acid excretion. Performed innocuously and controllable
to a nicety by dosage and by urine and blood tests.”
The “innocuousness” of Atophan has not been proved; on the other
hand there is evidence that it is not innocuous, as the recent
investigations of Hanzlik and Scott and their collaborators
(Cinchophen, Neocinchophen and Novaspirin in Rheumatic Fever,
J. A. M. A. 76: 1728 [June 18] 1921) show that it may injure the
kidney.
The circular also contains the following:
“No longer, hit and miss relief of pain at the expense of the
heart, the intestines, the kidneys and the nervous system, but
the promptest and most reliable analgesic, anti-inflammatory and
decongestive action so far known, with notable freedom from heart
depressant, renal irritant, constipating and cumulative toxic
by-effects. No contraindications, except chronic nephritis and the
presence of kidney concretions.”
This is misleading. The drug depresses the circulation, injures the
kidney and produces symptoms of salicylism or “toxicity.” It is _not_
the promptest and most reliable analgesic; morphin is superior and
salicylate is just as efficient. The phrase “decongestive action” is
vague. Treatment of pulmonary congestion from phosgene, and congestion
of the conjunctiva in mustard oil chemosis of cats, with large doses
of Atophan was ineffective; in fact, it proved distinctly harmful.
This was shown by such workers as Laqueur and Magnus, and Heubner
and Gildemeister (_Ztschr. f. d. ges. exper. Med._ =13=:200, 1921). It
is incorrect to ascribe “decongestive” or “anticongestive” action in
the true sense to Atophan (cinchophen). The principal assets of the
salicylate-cinchophen class of drugs in the treatment of rheumatism and
gout are their analgesic and antipyretic qualities.
The claim is made:
“In Rheumatic and Gouty Disorders, whether of the well-known
muscular and arthritic type, or their Eye, Ear, Nose and Throat
manifestations.”
The suggestion that Atophan is indicated in “their Eye, Ear, Nose and
Throat manifestations” is a vague generalization without definite
meaning, but nevertheless calculated to impress physicians and promote
the sale of Atophan for common and minor ailments. Rhinitis and sore
throat are, of course, self-limited conditions which require chiefly
good habits, personal and general hygiene as prophylactic measures,
and simple hot baths with rest, instead of medication, for symptomatic
relief. When it comes to ear and eye conditions, Atophan certainly
would do no good in otitis media, panophthalmitis, choroiditis,
retinitis, etc.
The administration of Atophan is proposed “in Migrains, Hemicrania,
Eyestrain, etc., often vaguely grouped as ‘Headaches.’” Eyestrain and
headaches are vague symptoms often arising from numerous causes that
require no medication, but rather good habits, hygiene and similar
corrective measures. There is always the possibility of habituation
from the use of drugs for such common and vague symptoms, resulting
eventually in more harm than good to the patient.
The use of Atophan is proposed “In Influenza (Grippe) for the ready
alleviation of the respiratory congestion, pain and stiffness of
limbs and back.” Probably the entire claim is without warrant, since
influenza is a self-limited disease. Atophan might relieve pain in
the joints, reduce the fever, etc., but at the same time it would
tend to impair the functional efficiency of the heart, which may be
impaired already by the disease. Cardiac failure is one of the causes
of death in influenza. The recommendation for “alleviating respiratory
congestion” is certainly without warrant, since in actual trial
in pulmonary congestion by Magnus et al., Atophan was found to be
deleterious and not beneficial. Phosgenized cats are probably as good a
test object for the alleged decongestive action of Atophan as anything
could be, since, according to Underhill and Ringer (J. A. M. A.
=75=:1531, 1920) the pathological physiology of the circulation and
respiration in phosgene poisoning and influenza are nearly identical.
Further, Atophan is recommended “In Pyorrhea Alveolaris as a systemic
support to local and specific measures.” Atophan is not indicated here.
Pyorrhea requires local medication, if anything at all. It could exert
no local beneficial effects in this condition; indeed, the employment
of Atophan might lead to irritation. Good dental treatment is more
essential than medication.
Finally, Schering and Glatz advise Atophan “In Eczema, Pruritus
and similar irritant and itching Skin Diseases with lowered blood
alkalinity.” The assumption that blood alkalinity is lowered in
irritant and itching disease is unsupported by evidence in medical
literature and the recommendation is incorrect and misleading. Neither
does Atophan alter the reaction of the blood. Amelioration in these
capricious conditions occurs without medication so that any relief
that might be obtained could not be attributed to Atophan. The entire
paragraph is misleading and will undoubtedly tend to extend the use of
Atophan in conditions for which it is not suited.--(_From Reports of
Council on Pharmacy and Chemistry, 1921, p. 8._)
UROTROPIN OMITTED FROM N. N. R.
Report of the Council on Pharmacy and Chemistry
Urotropin is a proprietary name applied to the substance which is known
in chemical literature as hexamethylenetetramin and which is designated
hexamethylenamine in the U. S. Pharmacopeia. The Council has authorized
publication of the following report explaining that Urotropin
was omitted from New and Nonofficial Remedies because Schering &
Glatz, Inc. (the firm that markets this brand of hexamethylenamin
in the United States), refused to place the U. S. Pharmacopeia
name Hexamethylenamine (hexamethylenamina) on the label and in its
advertising so as to make clear to physicians the identity of the
product, and, furthermore, because it was sold under therapeutic claims
which the Council held unwarranted.
W. A. Puckner, Secretary.
Commercial History of Hexamethylenamin
This substance which is generally referred to in chemical literature as
hexamethylenetetramin, the cyclic condensation product of formaldehyd
and ammonia, appears to have been described first in 1860 (Butlerow:
_Ann. d. Chem._ =115=:322, 1860). Subsequently, numerous references to
the preparation, properties and constitution of the substance appeared
in chemical literature.
Hexamethylenetetramin is said to have been first used for therapeutic
purposes by G. Bardet, who, in 1894, reported to the Société de
Thérapeutique that he believed this substance to be a uric acid
solvent. At about the same period, A. Nicolaier, who gave Bardet credit
for suggesting the use of hexamethylenetetramin as a uric acid solvent,
announced the discovery of its antiseptic action (_Centralbl. f. d.
med. Wissensch._ =32=:897, 1894; _Deutsche med. Wchnschr._ =21=:541,
1895). Shortly thereafter as a result of Nicolaier’s publication, the
Chemische Fabrik auf Aktien vorm. E. Schering, Berlin, Germany, began
to offer the product to the medical profession under the trademarked
and nondescriptive name “Urotropine.” In the United States, it was
marketed by Schering and Glatz, who then were acting as American agents
for the Schering works of Germany.
It soon became evident that hexamethylenetetramin was a valuable
drug. As the substance was introduced at a time when new “synthetic”
drugs were rapidly appearing and when unlimited and uncritical
confidence was placed in them, and before the medical profession became
skeptical of the claims advanced by manufacturers for their respective
“discoveries,” it was not long before this new drug was placed on the
market by many firms, each applying its own name and often keeping the
chemical character of it in the background. Some of the names which
were thus applied to hexamethylenamin were Cystogen, Aminoform, Formin,
Uritone, Urisol, {and} Cystamine.
In 1907 the late Prof. J. O. Schlotterbeck, then a member of the
Council, protested against the confusion caused by the marketing of a
given drug under different names. He stated that it was not uncommon
for a physician to prescribe two or more of these identical substances
in the same mixture, expecting to get the combined action of different
urinary antiseptics; also, that patients had been treated first with
hexamethylenamin under one name and later by the same substance under
another name (The Journal, Jan. 19, 1907, p. 241).
Hexamethylenetetramin was admitted to the eighth revision of the
U. S. Pharmacopeia. In part because of this official recognition
and standardization and in part because the extravagant reports of
its virtues had been largely discounted, physicians have in general
prescribed the drug by its pharmacopeial name, with one notable
exception: Urotropin. One reason for this is that Urotropin was the
first proprietary brand of hexamethylenetetramin introduced, a second
reason is that through the extensive and persistent advertising of
the proprietary name under which the substance was introduced, it has
become firmly fixed in the minds of many physicians. The other is that
the product was claimed to be of greater purity than the product sold
under the pharmacopeial or other name although no evidence confirmatory
of this claim has ever been published. On the other hand, Daniel
Base, as long ago as 1907, found that hexamethylenamin sold under its
pharmacopeial name is just as pure as when sold under proprietary
names. When, in 1907, urotropin was admitted to New and Nonofficial
Remedies, the published description showed that it was manufactured
by the Chemische Fabrik auf Aktien vorm. E. Schering, Berlin, and
that Schering and Glatz were the United States agents. In 1919, the
description was revised to show that Schering and Glatz were no longer
selling the German product.
As it is the general practice to omit articles that are admitted to
the U. S. Pharmacopeia for the reason that their quality is guaranteed
under the federal Food and Drugs Act and because pharmacopeial
nonproprietary articles are rarely advertised with claims that require
the Council’s control, yet, in the case of Urotropin, it was retained
because it was sold under a name not recognized in the pharmacopeia and
because special (proprietary) claims were made for it.
Urotropin Marketed Under Unwarranted Therapeutic Claims
The period for which Urotropin stood “Accepted” expired with the close
of 1921. To determine its continued eligibility for New and Nonofficial
Remedies, the Council examined the labels and circular matter sent by
Schering and Glatz for the purpose and also a booklet “Urotropin,”
subsequently sent by the firm to physicians.
It was found that the pamphlet contained a number of unwarranted
statements. Particularly objectionable are the claims made for the use
of Urotropin as an antiseptic in body fluids that are alkaline, such as
the cerebrospinal fluid, bile, aqueous humor of the eye, saliva, the
excretions caused by middle ear infection and other excretions of the
nasal, bronchial, laryngeal and mucous membranes. The lack of efficacy
of hexamethylenamin in alkaline secretions is generally admitted and
the clinical references to the use of hexamethylenamin in the pamphlet
are obsolete. In the introduction to the pamphlet, Schering and Glatz
state that they are well acquainted with the scientific research work
discrediting the efficiency of hexamethylenamin in nonacid mediums,
but that they feel that the accumulated evidence for its efficacy in
such conditions should not be “brushed aside.” However, the pamphlet
is not made up of quotations, but of unqualified statements. With one
exception, all references to the antiseptic properties of the drug in
alkaline mediums are previous to 1913, that is, before the importance
of reaction of the medium was fully appreciated. To quote these
earlier articles without regard to the later work, which in most eyes
discredited them, constitutes in effect an exploitation of this brand
of hexamethylenamin under unwarranted therapeutic claims.
Urotropin a Brand of Hexamethylenamine, U. S. P.
In consideration of the confusion which arises from the application
of different names to an identical article, the rules of the Council
provide that when an article which has been accepted for New and
Nonofficial Remedies is admitted to the U. S. Pharmacopeia under
another name, it will be retained, provided the official name is
given prominence on the label and in the advertising of such article.
Neither the label nor the advertising for Urotropin gives prominence
to the pharmacopeial name as a synonym nor indeed does it bring out
the fact that Urotropin is a brand of hexamethylenamine, U. S. P.
Schering and Glatz, Inc., was advised that Urotropin could be retained
in New and Nonofficial Remedies only on condition that the objections
to the therapeutic recommendations were removed and on agreement that
the U. S. P. name appear on the labels and circular matter. The firm
did not offer to make the product eligible for continued recognition;
accordingly the Council directed the omission of Urotropin because of
conflict with Rule 6 (Unwarranted Therapeutic Claims) and with Rule
8 (Objectionable Names).--(_From Reports of Council on Pharmacy and
Chemistry, 1921, p 71._)
STYPTYSATE NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report,
declaring Styptysate (Ernst Hischoff Co., Inc.) inadmissible to New and
Nonofficial Remedies.
W. A. Puckner, Secretary.
Styptysate, according to the advertisement of Ernst Bischoff Co., Inc.,
New York, is “obtained by dialysis from Bursa Pastoris (Sheppard’s
[_sic!_] Purse).” It is claimed to be “The Remedy For Hemorrhages,”
to be “Superior to Ergot and Hydrastis,” “of particular advantage
in Menorrhagia and Metrorrhagia” and to have been “found of great
value in vesical hemorrhages and hemorrhages from mucous membranes in
general.” The Styptysate label bears the synonym “Dialysate Herba Bursa
Pastoris”; the statement that it contains “alcohol 11 per cent.” and
that it is “made in Germany.” No other statement of the composition or
strength of “Styptysate” is furnished nor is the name of the German
manufacturer disclosed.
In an advertising circular entitled “Styptysate, a New Reliable
Hemostatic,” it is declared that in recent years the plant, Shepherd’s
Purse (_Capsella bursa pastoris_), “has been submitted to clinical
tests in the form of a concentrated dialysate, known as Styptysate,
by Loewy, Oppenheim, Krummacher and others, and that their reports
coincide in regard to Styptysate as a hemostatic _par excellence_,
particularly in uterine hemorrhages, even in cases where ergot and
hydrastis had failed to produce satisfactory results.” The circular
also reprints some “short clinical reports” without reference to their
authorship; one ascribed to Krummacher and two ascribed to “B.H.M.,
Kansas City, Mo.,” and the following references: “A. Krummacher, M.D.,
_Monthly Review for Obstetrics and Gynecology_, Berlin, Vol. XLIX, 4,
and Vol. LII.” “H. Oppenheim, M.D., _Medical Clinic_, Berlin, 1920, 35.”
Shepherd’s Purse is a weed common in the United States and in Europe.
Like most other herbs, it has some reputation as a folk medicine. It
is used by eclectics and homeopaths, being included in the Homeopathic
Pharmacopeia of the United States. Shepherd’s Purse receives no
consideration at the hands of the authors of standard works on materia
medica, pharmacology or therapeutics.
From an examination of recent German medical publications, it appears
that the use of Shepherd’s Purse was proposed as a substitute for
ergot and hydrastis, when the latter drugs became scarce in Germany.
These publications, in the main, emanate from those in the employ of
pharmaceutical firms and deal with proprietary preparations or they are
written by physicians who used these proprietary preparations at the
solicitation of the manufacturers. For this reason the reported results
must be accepted with reserve.
One of the proprietary preparations discussed in the German
publications is Styptysate, manufactured by Isalfabrik Johannes
Buerger, Wernigerode. It is said to be produced by submitting the juice
of fresh Shepherd’s Purse to dialysis and preserving the dialysate
by the addition of alcohol. There is no statement as to the drug
strength or the chemical or biological standards, if any, used in
its manufacture; hence, the preparation is essentially a secret one.
As first produced, the preparation seems to have been fortified by
the addition of cotarnin: the dose was then given as ten to fifteen
drops. Later, as the cost of cotarnin went up, this drug was omitted,
and the drug strength increased; the dose of the new preparation is
given as twenty-five to thirty drops. Just what relation, if any, the
Styptysate of Ernst Bischoff Co., Inc., bears to that of the Isalfabrik
Johannes Buerger, Wernigerode, cannot be determined from the Bischoff
advertising. If it has any relationship the announcement that no
narcotic order is required when ordering Styptysate would indicate
that the new preparation is supplied; the old one with its addition
of cotarnin would require a narcotic order. On the other hand, the
recommended dose of the cotarnin-free preparation is twenty-five to
thirty-drops, whereas the product sold by Bischoff and Co. is to be
given in doses of ten to fifteen drops--that is, in the amount proposed
for the cotarnin-fortified product.
What justification is there for the claim that Styptysate has been
submitted to clinical tests by Loewy, Oppenheim and Krummacher and
found to be a hemostatic _par excellence_ and efficient even where
ergot had failed to give satisfactory results? Loewy (_Zentralblatt
für Gynäcologie_ =42=:920, 1921) made some pharmacologic tests on
guinea-pigs with the cotarnin-containing preparation, but reported no
clinical trials. Hans Oppenheim (_Medizinische Klinik_, Aug. 29, 1920,
p. 906) reported that he was agreeably surprised at the excellent
results (_vorzueglichem Erfolg_) obtained with the drug but he did not
assert that it is superior to ergot.
Krummacher reported on thirteen cases of profuse menstruation in
which the patients were treated with Styptysate, using for a part,
the preparation containing cotarnin and for the other a preparation
without cotarnin. He reported as good results with the cotarnin-free
preparation in larger dosage, as with the cotarnin-containing
preparation in smaller dosage. Krummacher did not compare Styptysate
with ergot. Some of Krummacher’s cases are quoted, with some
typographical errors, in the Bischoff circular.
On the assumption that the product discussed in German publications
is the Styptysate marketed in the United States, the best that can be
said for it is, that during a shortage of ergot it was used in place
of that established drug. There is no evidence to warrant the use of
this indefinite proprietary in place of the biologically standardized
fluidextract of ergot or other standardized ergot preparations.
Styptysate (Ernst Bischoff and Co., Inc.) is inadmissible to New
and Nonofficial Remedies because its composition is semisecret and
indefinite and there is no evidence that its uniformity and strength
is controlled (Rules 1 and 2); further, it is inadmissible because the
therapeutic claims advanced for it are exaggerated and unwarranted
(Rule 6) and because there is no evidence that it possesses any
advantage over established drugs such as the biologically standardized
fluidextract of ergot or the definite ergot preparations admitted to
New and Nonofficial Remedies.--(_From The Journal A. M. A., Feb. 11,
1922._)
LIPOIDAL SUBSTANCES (HOROVITZ) NOT ADMITTED TO N. N. R.
Report of the Council on Pharmacy and Chemistry
The Council has authorized publication of the following report
declaring Lipoidal Substances (Horovitz) inadmissible to New and
Nonofficial Remedies because its composition is essentially secret
and because the curative claims made for it are unsubstantiated and,
therefore, unwarranted.
W. A. Puckner, Secretary.
In the advertising of the Horovitz Biochemic Laboratories Co. (A. S.
Horovitz, president) we read:
“Horovitz proves by careful paralleled investigations of normal
and of pathological tissues, both in addiction disease and in
other diseases, that in patients suffering from narcotic addiction
disease there is an inactivity of the lymph-glands due to the
use of the drug and that the system is not supplied with the
necessary fats.” “Horovitz further found that the lipoidal content
of the cerebro-spinal system varies in strict accordance with the
pathological processes introduced by infection or by alkaloids.
Furthermore, he has found that the lipoids of various other organs,
as well as those of the THERMORnervous system, may be extracted and
consumed by the administration of narcotic alkaloids.”
It is further stated in the advertising that:
“After a long and very careful research investigation, Dr. Horovitz
worked out a method of rational treatment for narcotic addiction
disease which involves the restoration of the lipoids, which have
been lost through the action of the drug, and of the toxins, by
means of a combination of lipoidal substance from various plant
lipoids in the form of a sterile solution. This preparation not
only replaces the lipoids lost by the tissues, but also protects
the nerve tissues, from attacks by the toxins elaborated during the
use of narcotics, and, this by detoxicating the tissues, brings
about permanent freedom from the craving of narcotics, instead of
the temporary relief afforded by other methods of treatment.”
The “combination of lipoidal substance of various plant lipoids” which
was worked out by Horovitz, the Horovitz Biochemic Laboratories offer
as “Lipoidal Substances.” This preparation is supplied in ampoules said
to contain 1 c.c. of solution. The treatment with “Lipoidal Substances”
consists, first, in the complete withdrawal of the narcotic; second,
in free catharsis; and third, in the intramuscular injection of the
preparation. The initial dose is given as 8 to 12 minims repeated with
increase of 3 to 4 minims every three hours during the first day. On
the second, third and fourth day 16 minims is to be given twice a day
and “from the fifth day until the medication is stopped (usually 28 to
35 days) it will be necessary usually to give but 1 injection of 16
minims each day.”
In a request for the admission of its preparation to New and
Nonofficial Remedies, the Horovitz Biochemic Laboratories Co. stated:
“The composition of Lipoidal Substance is (_a_) Lipoids of plant
origin, (_b_) Vitamines (water soluble) of plant origin, (_c_)
Non-specific plant proteins, (_d_) Preservatives--None.”
While the communication abounded in generalities, it gave neither
the identity nor character of the lipoids, of the vitamins nor of
the nonspecific protein, nor their quantities or methods for their
control. The firm presented no evidence that the injection of “Lipoidal
Substances” produced any effect other than by suggestion. Also,
while a long list of references to publications bearing on lipoids
was submitted (many of which had no bearing on the subject under
consideration) there was no reference to the work of Horovitz quoted in
the firm’s advertising.
After examining the information which had been submitted, the Council
requested the manufacturer to supply:
1. Information as to the character (identity) of the several
ingredients contained in the preparation that it marketed, the amount
of each ingredient so far as known and the method used for their
control.
2. Evidence that the administration of “Lipoidal Substances” is of
value in the treatment of drug addiction.
3. Evidence for the claims that the “researches” of Horovitz have
proved that “in patients suffering from narcotic addiction disease
there is an inactivity of the lymph-glands ... and the system is not
supplied with the necessary fats” and that “lipoidal content of the
cerebro-spinal system varies in strict accordance with the pathological
processes introduced by infection or by alkaloids” and that “the
lipoids of various other organs as well as those of the nervous system,
may be extracted and consumed by the administration of narcotic
alkaloids.”
The Horovitz Biochemic Laboratories replied that the requested
information would be supplied in about _two weeks_. At the expiration
of _three months_ the promised information and evidence had not been
received; neither had any reports to show the value of the treatment
come to the attention of the Council. The Council, accordingly,
declared “Lipoidal Substances” (Horovitz Biochemic Laboratories)
inadmissible to New and Nonofficial Remedies because the composition is
essentially secret and because the curative claims are unsubstantiated
and unwarranted.--(_From The Journal A. M. A., Feb. 25, 1922._)
YEAST PREPARATIONS AND VITAMIN B CONCENTRATES
Report of the Council on Pharmacy and Chemistry
The Council has adopted the following principles as a guide in the
consideration of yeast preparations and vitamin B concentrates for New
and Nonofficial Remedies.
W. A. Puckner, Secretary.
1. The claim that deficiency of vitamin B and diseases resulting
therefrom are common conditions in the United States is not at this
time supported by adequate acceptable evidence.
2. The claim that yeast preparations or extracts are, in principle
or in general, essentially more effective or more practical or more
available means of administering vitamins than the commonly available
vitamin-containing foods is not at this time supported by adequate
acceptable evidence. (Any claims for superiority made for such products
proposed for inclusion in New and Nonofficial Remedies must be
presented in detail and passed on specially by the Council.)
3. The claim that therapy with yeast or yeast preparations has as yet
more than an experimental status is not at this time supported by
adequate acceptable evidence.
Preparations for which such claims are made, directly or by implication
or in one-sided quotations, in advertisements or letters or by
salesmen, cannot be admitted to or retained in New and Nonofficial
Remedies.--(_From The Journal A. M. A., April 15, 1922._)
PART II
CONTRIBUTIONS FROM THE A. M. A. CHEMICAL LABORATORY
FOREWORD
THE CHEMICAL LABORATORY OF THE AMERICAN MEDICAL ASSOCIATION
The Chemical Laboratory of the American Medical Association was
established in 1906 to assist the Council on Pharmacy and Chemistry in
the investigation of proprietary remedies.
In accordance with the principle of its foundation, the Laboratory
examines and checks the claims made for the composition and chemical
properties of the products under examination by the Council, and when
these are admitted to New and Nonofficial Remedies, it insures the
establishment of tests and standards whereby the identity and purity of
these products may be controlled. In addition, the Laboratory supplies
information, secured by reference to chemical and pharmaceutical
literature or by actual analytic work, in regard to proprietary and
unofficial medicines, either for publication in _The Journal of the
American Medical Association_ or through direct correspondence.
Those portions of the Laboratory’s activities which are of special
interest to physicians and which were not included in the Reports of
the Council on Pharmacy and Chemistry were included in the Propaganda
for Reform in Proprietary Medicines, ninth edition (1916), so far as
they had been published up to the time when the edition was issued;
those made during the last five years are included in Part II of this
volume.
For a detailed report of the Laboratory’s work, the reader is
referred to the article that follows on “The Work of the American
Medical Association Chemical Laboratory.” Those who are interested
in the analysis of drugs are referred to the Reports of the Chemical
Laboratory issued annually for the details of the analyses which have
been made by the Laboratory.
THE WORK OF THE AMERICAN MEDICAL ASSOCIATION
CHEMICAL LABORATORY[E]
W. A. Puckner, Phar.D.
[E] Read before the Section on Pharmacology and Therapeutics at the
Sixty-Seventh Annual Session of the American Medical Association,
Detroit, June, 1916.
The American Medical Association Chemical Laboratory was established
nearly ten years ago--in fall of 1906. The reason for its existence
was primarily the fact that the Council on Pharmacy and Chemistry
found it difficult to secure from outside sources such help as it
needed in checking up the composition and properties of proprietary
medicines under investigation. Medical schools and similar institutions
were found ready to lend their assistance in pharmacologic and
medical investigations; but the chemical investigation required the
establishment of a laboratory under the control of the American Medical
Association.
As years have passed, the scope of the laboratory has been extended:
Its services have been requisitioned by The Journal in various
ways. Thus, when requested, the laboratory reviews and verifies the
chemical data contained in editorials and original contributions. The
laboratory is often called on for information as to the character and
composition of quack treatments and so-called “patent medicines.”
Through the columns of The Journal and through direct correspondence,
the laboratory responds to requests of physicians with information
regarding the composition of medicines which they prescribe or in which
they are interested. The laboratory attempts to be to the members of
the American Medical Association what the prescription pharmacist is,
or should be, to the prescribing physician--a storehouse of chemical
and pharmaceutical information. In the belief that an insufficient
familiarity with the chemistry and pharmacy of drugs constitutes
the chief reason for the extensive use of unscientific, worthless
or fraudulent proprietary remedies, this service is rendered by the
laboratory as a contribution to the cause of rational therapy.
Since the efficiency of the American Medical Association Chemical
Laboratory will increase as its activities are better known, the
following more detailed statement of its work is offered:
THE LABORATORY AND THE COUNCIL
As stated in the rules of the Council on Pharmacy and Chemistry, it is
“manifestly impossible for the Council to investigate the composition
of every complex pharmaceutical mixture ...”; “it can only give an
unbiased judgment on the available evidence.” In line with this, the
laboratory does not undertake to prove the composition of constitution
of all new synthetics, nor does it attempt to determine the individual
composition of proprietary mixtures. It checks all claims that seem
doubtful, however, and uses its best endeavors to secure correction of
misstatements with regard to proprietary remedies and improvement in
the quality of these products. Further, it reexamines, when this seems
desirable, the products which have been admitted by the Council to New
and Nonofficial Remedies, and thus determines, from time to time, their
dependability. The fact that no product admitted to New and Nonofficial
Remedies has later been shown to be untrue to its claimed composition
is, it is believed, an indication that in this respect the laboratory
has succeeded in performing the work for which it was primarily created.
In this connection the question may be asked, Are many proprietary
medicines exploited to the medical profession with false claims in
regard to their composition? Also it may be asked, Has the number of
proprietaries marketed with false statements of composition decreased
since the Council and the laboratory began their work? Answering the
latter question first: There is no doubt that today fewer proprietary
medicines are being sold with false claims as to composition than
there were ten years ago. When the Council began its work, medical
journal advertising teemed with statements regarding the composition
of medicines which any chemist familiar with medicine would not
hesitate at sight to brand as untrue. Today such manifestly false
claims are rare. Coming to the former question: Many false statements
regarding the identity and composition of remedies have been made in
ignorance. This is not surprising when it is remembered that the most
ignorant may and do engage in the manufacture of medicine. Besides
ignorance, however, an accommodating conscience on the part of the
manufacturer and a failure on the part of the medical profession to
appreciate the danger which lies in the use of medicines of unknown
composition unquestionably have greatly encouraged the marketing of
falsely declared medicines. A glaring illustration of the ignorance
of manufacturers--for it is hard to believe that any business concern
would deliberately court prosecution by the federal authorities through
false statements on labels--is the fact that nearly thirty years ago
A. B. Lyons published a report[147] pointing out that the proprietary
Iodia was falsely declared as to composition and that in 1914 when the
Council examined this preparation such incorrect declaration appeared
on the label.[148] That many physicians do not recognize the danger
to their patients and their reputation in the use of medicines, the
composition of which they do not know, is illustrated by the fact,
disclosed by inquiries sent to the laboratory, that physicians were
found willing to employ an arsenical preparation (Venarsen), advertised
for intravenous use, although its promoters vouchsafed no information
in regard to the nature of the arsenic compound contained therein.
[147] Lyons, A. B.: Detroit Lancet, 1882, 6, 157.
[148] The Journal A. M. A., Nov. 21, 1914, p. 1871.
UNRELIABILITY OF LITTLE USED DRUGS
The purpose of the federal Food and Drugs Act is to secure the
prosecution and punishment of all who sell medicines which are
adulterated or misrepresented as to composition. As a matter of fact,
the wording of the law relating to the adulteration and misbranding of
drugs is such that the federal authorities have been able to do little
more than to require that the drugs for which standards are provided
in the Pharmacopeia shall when sold comply with those standards.
Similarly, those states which attempt to improve the quality of drugs
sold within their borders--few states do efficient work along these
lines--limit their work to the enforcement of the Pharmacopeial
standards. This leaves the vast number of unofficial drugs and
medicaments beyond the control of federal or state authorities.
While most of these drugs are relatively unimportant, and while the
amounts of them which are used are not great individually, the total
consumption of them is large. With a view of furnishing to physicians
standards for drugs of this sort the Council has described in New and
Nonofficial Remedies not only distinctly proprietary drugs, but also
some of the unofficial drugs which are apparently of therapeutic value
and used to a considerable extent. Aiding the Council in this line of
endeavor, the laboratory has attempted to establish standards for these
little used drugs, and New and Nonofficial Remedies, 1916, provides
standards for such unofficial and non-proprietary drugs as quinin and
urea hydrochlorid quinin, tannate, sodium acid phosphate, and sodium
perborate. An example of work which furnished much needed standards
for an unofficial article is the investigation of zinc permanganate
by W. S. Hilpert.[149] Reference to the published reports of the
laboratory will give an idea of the amount of work such standardization
entails. A reference to the new U. S. Pharmacopeia, when this comes
from the press, will show that a considerable number of unofficial
articles described in New and Nonofficial Remedies have been admitted
to the Pharmacopeia along with the standards worked out in this
laboratory.
[149] Zinc permanganate, J. A. M. A., Feb. 6, 1909, p. 488; Reports
Chem. Lab. =2=:15, 1909.
While in a way the work done in connection with these less important
drugs has attracted little attention from the medical profession,
it has had an effect on pharmaceutical manufacturers. In the past,
pharmaceutical houses, ever anxious to market something new, on the
slightest provocation have placed on the market, in the form of pills,
powder, elixir, ampule, etc., every drug for which some sort of medical
recommendation could be found. In marketing these dosage forms, the
manufacturer has too often been little concerned about the quality of
the drugs used.[150] Just at present, for instance, some interest is
being shown in iron cacodylate; but while manufacturers appear to be
most ready to take advantage of this interest by offering the drug
in the form of ampules, etc., they have given little help toward the
establishment of standards for this arsenic compound. Manufacturers are
ever ready to sell drugs of all sorts, but in view of the small demand
they cannot or will not safeguard the identity and purity of such
drugs. A further illustration of the unreliability of unofficial drugs
is the recent report by Levy and Rowntree[151] showing not only that
the various dosage forms of emetin hydrochlorid obtained from different
manufacturers varied from manufacturer to manufacturer, but also that
the product of the same manufacturer was variable and that the supply
furnished by one pharmaceutical firm was so toxic as to make its use
dangerous.
[150] The Unreliability of Unimportant Medicaments, The Journal
A. M. A., Sept. 28, 1912, p. 1156.
[151] Levy, R. L., and Rowntree, L. G.: On the Toxicity of Various
Commercial Preparations of Emetin Hydrochlorid, Arch. Int. Med., March,
1916, p. 420.
THE ANALYSIS OF “PATENT MEDICINES”
In the preface to the first annual report of the chemical laboratory
it was stated that the laboratory “occasionally takes up the
examination of ‘patent medicines’ ...” At that time it was felt that
the widespread use by the medical profession of irrational and even
secret medicines made it necessary to devote the laboratory’s attention
to the correction of this evil. As the years have passed on, these
conditions have been remedied to some extent, at least so far as
chemical analysis can correct them. On the other hand, public opinion
has been aroused to the many evils connected with the exploitation of
“patent medicines,” and has more and more insistently demanded that the
medical profession aid in the correction of this evil. Accordingly,
the laboratory has paid much attention to the analysis of “patent
medicines” during the last few years. As the chief asset of “patent
medicines” is the element of secrecy which surrounds their composition,
it is hoped that the laboratory’s analysis of such widely used “patent
medicines” as Nature’s Creation,[152] Mayr’s Wonderful Stomach
Remedy,[153] Sanatogen,[154] Eckman’s Alterative,[155] Tonsiline,[156]
and Bromo-Quinin[157] has been worth the labor. In addition, the
work of this laboratory has been published, including not only the
results of its analyses, but also the methods which are used. In view
of the dearth of published reports regarding the methods used in the
analysis of “patent medicines,” it is hoped that this feature of the
laboratory’s work has been of aid to chemists engaged in similar work.
[152] The Journal A. M. A., March 5, 1910, p. 806.
[153] The Journal A. M. A., Aug. 19, 1911, p. 671.
[154] The Journal A. M. A., April 20, 1912, p. 1216.
[155] The Journal A. M. A., April 27, 1912, p. 1298.
[156] The Journal A. M. A., April 4, 1914, p. 1109.
[157] The Journal A. M. A., Nov. 27, 1915, p. 1932.
The laboratory’s activities along these lines have done much to
discount the claim of proprietary manufacturers that chemical analysis
is unable to determine the character of “patent medicines.” The recent
Wine of Cardui trial has brought it out prominently that chemical
analysis can determine the presence of potent constituents, and that
“patent medicines” which fail to reveal such potent ingredients to the
analyst may safely be put down as worthless. The demonstration that
the essential composition of medicinal preparations may be determined
by chemical analysis should also prove an effective answer to the
manufacturers in their protest against the requirement, now being
urged for enactment into law in various states, that the medicinal
ingredients of their wares must be declared on the label. Manufacturers
have held that this would lay them open to competition with imitations
and substitutions. The possibility of chemical identification proves,
however, that secrecy of composition, though it prevents consumers from
knowing the character of a “patent medicine,” will not be a hindrance
to the imitator and substitutor.
IDENTITY OF DRUGS USED IN INVESTIGATIONS
In the past, much of the experimental work in medicine has seriously
suffered in that the identity of the material used in such
investigations was not established. In view of this the laboratory
has watched the contributions submitted to The Journal, and whenever
necessary and feasible has urged the authors to identify their material
before publication of the findings. For instance, a number of staining
agents--so-called “anilin dyes”--have been found to possess therapeutic
action. Since the identity of many of these staining agents is today
essentially secret, the laboratory has urged through The Journal that
those who experiment with these substances make an effort to determine
their identity whenever possible and to give preference to those the
chemical identity of which is known. The need for such identification
has been discussed in the reports of the laboratory.[158] The amount
of work involved in the chemical identification of drugs used for
experimental work is illustrated in a contribution entitled “An
Examination of Several Commercial Specimens of Opium Alkaloids or Their
Salts.”[159] by L. E. Warren, in which was determined the identity of
the various opium products used in an investigation by D. I. Macht,
carried out under a grant of the Therapeutic Research Committee.
[158] Reports A. M. A. Chemical Laboratory, 1912, v, 102.
[159] Am. Jour. Pharm., 1915, 87, 439.
THE LABORATORY AND PHARMACEUTICAL LITERATURE
In the past much of the information in regard to the composition
and properties of medicines which has appeared in pharmaceutical
journals has not become available to medicine. In many cases medical
journals could not afford to publish such data because this would have
been contrary to the interest of their advertisers, and hence the
publications regarding the irrational character of Lactopeptine, of
Bromidia, etc., which appeared in the pharmaceutical journals did not
become a matter of common medical knowledge. Through the laboratory
an attempt has been made to keep the medical profession informed in
regard to pharmaceutical literature. The laboratory has a good working
pharmaceutical and chemical library, and subscribes to the important
American and foreign pharmaceutical and chemical publications. The
discussion of new remedies, such as medinal and sodium veronal,[160]
salvarsan, atoxyl and arsacetin,[161] and neosalvarsan[162] soon after
their introduction, illustrates the work of the laboratory along these
lines.
[160] The Journal A. M. A., Jan. 23, 1909, p. 311.
[161] The Journal A. M. A., Dec. 31, 1910, pp. 2303 and 2314.
[162] The Journal A. M. A., Oct. 5, 1912, p. 1295.
THE LABORATORY’S EFFORTS TOWARD RATIONAL PRESCRIBING
The laboratory naturally is in thorough sympathy with the present day
efforts toward a more rational use of drugs, as exemplified in the
Council’s publication “Useful Drugs.” Two recent contributions of
the laboratory may be cited as a further support of the movement for
limiting prescribing to the more widely used drugs. In line with the
general tendency of manufacturers to put out all sorts of modifications
and asserted improvements over official substances, there have been
placed on the market a number of preparations said to represent some
improvement over the pharmacopeial Blaud pills. The report, “The
Quality of Commercial Blaud’s Pills,”[163] by L. E. Warren, shows that
the ordinary pharmacopeial Blaud pill is in every way the equal of the
semiproprietary preparations claimed to be improvements. Further, the
examination of the various brands of sodium and theobromin salicylate
as compared with the preparation diuretin by P. N. Leech[164] shows
that the former preparations, sold at 35 cents per ounce at the time
the examination was made, are fully the equal of the proprietary
Diuretin, which then cost the druggist $1.75 per ounce.
[163] The Journal A. M. A., April 17, 1915, p. 1344.
[164] The Journal A. M. A., April 4, 1914, p. 1108.
THE LABORATORY AS AN INFORMATION BUREAU
It is generally admitted that the proprietary medicine business,
particularly the exploitation of complex mixtures, attained the
extensive vogue which it has or had because instruction in medical
schools was deficient in materia medica, pharmacy and chemistry. As a
result of lack of knowledge along these lines, the young graduate after
some trial became fearful of formulating his own prescriptions, and in
time became dependent on pharmaceutical firms which provided him with
medicines ready to dispense. That physicians have been insufficiently
trained in regard to the pharmacy and chemistry of drugs has often been
emphasized in pharmaceutical journals where prescriptions containing
incompatible drugs are reported and where even plans are brought
forward whereby the pharmaceutical profession may aid in remedying this
difficulty.
During my pharmaceutical experience I was often sorely vexed as to what
to do when prescriptions contained drugs which on mixing would undergo
decomposition which the physician surely did not anticipate. I remember
well a prescription directing that potassium permanganate be made into
pills with extract of gentian and other things, and how, the physician
having spurned the suggestion to modify the prescription so as to avoid
decomposition of the permanganate, I was obliged to select a mortar,
gently triturate the drugs until a conflagration was started, and to
finish the prescription after the combustion had subsided. However,
in my pharmaceutical experience I generally found the physician most
ready to receive suggestions from the pharmacist which would prevent
incompatibilities, improve the palatability and appearance of his
prescriptions, and protect the patient from unnecessary expense.
Similarly it has been my experience since the establishment of the
Association’s laboratory that physicians are anxious to receive
information in regard to the materia medica, pharmacy and chemistry
of drugs. As the druggist earns the respect and support of the
physician when he makes available to him the pharmaceutical knowledge
and experience which he has, so this laboratory has aimed to gain
the endorsement of the American Medical Association membership by
furnishing to physicians information in regard to the composition,
chemistry and pharmacy of drugs through replies in the Query and
Minor Notes Department of The Journal as well as through direct
correspondence. It has been most gratifying to the laboratory that The
Journal receives an increasing number of inquiries both as regards
the chemical and pharmaceutical questions involved in the writing of
prescriptions and as regards the composition of secret and semisecret
proprietaries (often because they are prescribed by the inquirer’s
colleague) and “patent medicines” (which are taken by his patient). The
laboratory has tried its best to answer the many inquiries received.
Many of the questions which come in can be answered by a pharmacist or
chemist without hesitation. Others, particularly as to the composition
of medicines, the laboratory has been able to answer by reference to
its library and its extensive card index. Still others have required
experimentation and chemical analysis.
While, as stated a moment ago, the laboratory has encouraged the
sending of inquiries and has earnestly striven to furnish the
information asked for, it is obvious that the amount of chemical work
which can be done is limited. The small size of the laboratory force,
consisting of three chemists engaged in actual analytical work, makes
it necessary to select for investigation those problems which shall
be of general interest to the medical profession. As the American
Medical Association is national in its scope, the laboratory has held
that it can do analytical work only when such work will be of general
interest to physicians and of value both to the medical profession
and the public. In view of this it has refrained from undertaking
analyses which would benefit only the physician making the inquiry and
possibly his patient. The laboratory further has not felt justified
in undertaking work of merely local interest; instead it has used
its endeavors to secure the investigation of such local problems by
municipal or state authorities.--(_From The Journal A. M. A., Nov. 25,
1916._)
LEAD IN “AKOZ”
Akoz is a mineral product sold by the Natura Company of San Francisco,
and said to possess most remarkable medicinal properties.
A circular issued by the Natura Company begins thus:
“While scientists have been striving through the centuries to
compound remedies for man’s various ills, Nature, greatest chemist
of them all, has been working wonders in her crucibles and has
achieved results far beyond man’s greatest expectation.”
“Nature’s chief handicap has been the difficulty of placing her
gifts in the hands of those whom she would benefit. By accident or
fate, as you will, one of Nature’s greatest medicinal products has
just been discovered. It is the mineral given the name of Akoz by
John D. Mackenzie, president and manager of the Natura Company of
San Francisco, which is now giving this rare remedy of Nature to
the public.”
The circular then describes how the power of the “rare remedy” to cure
rheumatism is claimed to have been discovered and asserts that:
“Akoz was subjected to every known scientific test before being
presented to the public. It was practically determined that the ore
contained a new element having radium-like qualities but containing
nothing poisonous or harmful.”
“After the curative virtues of Akoz for rheumatism, stomach
trouble, eczema, catarrh, piles, ulcers and numerous other ailments
had been fully established in chemical laboratory, hospital clinic,
and the private practice of physicians in various parts of the
world, Mr. Mackenzie effected the organization of the Natura
Company.”
This product, put up in the form of “Akoz Medicinal Mineral Water, Akoz
Ointment, Akoz Powder and Akoz Suppositories,” was submitted to the
Council on Pharmacy and Chemistry for consideration some years ago with
the claims that “Akoz” itself consists essentially of zinc sulphid,
barium sulphate and aluminum oxid. The submitted analysis did not
declare the presence of lead or of uranium though “special tests” for
the latter had been “run.” Without checking the claimed composition,
the Council at that time refused recognition to Akoz because there
was no evidence submitted for the very extravagant and altogether
improbable therapeutic claims.
After the Council had concluded the consideration of Akoz a letter
was received from a California physician stating that according to an
analysis submitted to him Akoz contained 0.34 per cent. of lead in the
form of lead sulphate. The correspondent held that, while the lead
sulphate did not pass into solution, persons drinking the supernatant
liquid from Akoz (the “medicinal mineral water” is made by adding Akoz
to ordinary water) might inadvertently swallow some of the powder. He
was inclined to believe that this might account for a case of lead
poisoning which had been observed in a patient who had been taking Akoz.
Inasmuch as it has been demonstrated by Carlson and Woelfel (Carlson,
A. J., and Woelfel, A.: Solubility of Lead Sulphate and Basic Lead
Carbonate in Human Gastric Juice.... In Hygiene of the Painter’s
Trade by Alice Hamilton, Bull. of U. S. Bureau of Labor Statistics
No. 120, May 13, 1913, pp. 22-32) that even small quantities of lead
sulphate when taken into the system for a long time, have produced lead
poisoning, the laboratory deemed it important that the products be
examined for lead.
A specimen of “Akoz Powder” submitted to the Council by the Natura
Company and contained in a sifter-top can was taken for analysis. The
contents of the can were thoroughly mixed. To determine the presence of
lead some of the powder was extracted with ammonium acetate solution.
Details of Analysis
Qualitative tests showed the presence of lead and sulphate in the
ammonium acetate solution.
The presence of lead was demonstrated by the black precipitate with
hydrogen sulphid, the yellow precipitate with potassium chromate and
the typical yellowish crystalline precipitate with potassium iodin.
The presence of sulphates in the ammonium acetate solution was shown by
the formation of a precipitate with barium chlorid solution and acetic
acid.
Two 2 gm. samples (A and B) were taken for the quantitative
determination of lead. Each was treated repeatedly with a saturated
solution of ammonium acetate until the filtered ammonium acetate
solution gave no appreciable precipitate with potassium chromate
solution. The ammonium acetate extractions from each specimen were
combined and treated with hydrogen sulphid, the precipitated lead
sulphid filtered off and washed, and ignited with sulphuric acid at a
low heat. The crucible with the residue of lead sulphate was cooled and
weighed.
A yielded 0.0469 gm., or 2.34 per cent., lead sulphate.
B yielded 0.0440 gm., or 2.20 per cent., lead sulphate.
While the laboratory has no evidence to show that the amount of
lead-sulphate thus found to be present is likely to prove harmful, the
following cautionary letter was sent to the Natura Company:
“According to information which you sent to the Council on Pharmacy
and Chemistry your product “Akoz” does not contain lead. In
view of reports received ascribing symptoms, resulting from the
internal use of Akoz, to chronic lead poisoning, an examination
of a specimen of Akoz Powder, which you sent to the Council, was
made. This examination indicates the presence in Akoz Powder of
about 2.2 per cent. lead sulphate. In view of the disastrous
results likely to follow the internal use of products containing
even small amounts of lead, the above is submitted to you for your
consideration.”
No reply to the foregoing was received from the Natura Company.--(_From
Reports A. M. A. Chemical Laboratory, 1916, p. 103._)
SODIUM ACETATE IN WARMING BOTTLES
Recently the laboratory’s attention was called to the “ThermoR
Waterless Hot Bottle,” manufactured by the Royal Thermophor Sales
Co., New York. The following claims appear in one of the advertising
pamphlets:
“There is moist heat.” “Rubber hot-water (? ? ?) naturally give a
_moist_ heat.” It (ThermoR) gives a _dry_ heat.
“The ‘THERMOR’ Bottle is _not_ a hot-water bottle--it acts on a
principle that is entirely different and new.”
“... gives you _first, last and all the time_ a fixed degree of dry
usable heat--a heat that holds steadily at 125 degrees for fully
twelve hours--you will easily see why it is that ‘THERMOR’ relieves
and cures where hot-water bottles fail.”
The bottle was nickel plated, 8-3/8 inches in diameter and 1-1/2 inches
thick, and in appearance resembled an exaggerated closed Ingersoll
watch.
The bottle is not flexible and weighs 3-1/2 pounds. The contents
consisted essentially of sodium acetate. This salt melts when heated.
When it cools the temperature inside the bottle is relatively
constant, as it will remain at the “freezing point” until all of
the sodium acetate has solidified. The duration of the time that it
remains warm when well wrapped is simply in inverse proportion to the
conductivity of the surrounding environment. When two ordinary towels
were carefully arranged about it, the air between the bottle and the
wrappings was maintained at a temperature of 40-50 C. (104-122 F.) for
a period of eight hours.
The company’s implication that the heat given out by the Thermor
bottle differs from that given out by an ordinary hot-water bottle is
an absurdity. The use of sodium acetate in the preparation of warming
bottles has been in practice many years, and is not “a principle that
is entirely different and new.” Furthermore, the therapeutic claims
are extravagant.--(_From Reports A. M. A. Chemical Laboratory, 1916,
p. 105._)
ANTI-SYPHILITIC COMPOUND (SWEENY)
A specimen of Anti-Syphilitic Compound (Sweeny), sold by The National
Laboratories of Pittsburgh, was received from a physician. The package
(1 ounce size) has been opened by the sender and about three fourths of
the contents removed.
From the rather indefinite statements in the literature of the
manufacturer it is gathered that the preparation is claimed to be a
“sterile, oily emulsion” which contains 1/20 grain of mercuric benzoate
in each 5 minims, together with some sodium chlorid. According to
information furnished by the Laboratory’s correspondent, the price
asked for the preparation is $15 an ounce.
The quantity of the preparation received was too small to permit a
complete examination, but, from the tests which it was possible to
make, the preparation appears to be an aqueous solution containing
some suspended matter and small quantities of mercuric benzoate
and a chlorid, presumably sodium chlorid. There was no evidence of
the presence of an “oily emulsion.” Quantitative tests indicated
the presence of a mercuric salt, equivalent to about 0.2783 gm. of
crystallized mercuric benzoate per 100 c.c. This corresponds to about
0.00086 gm. in each 5 minims, or about 26.5 per cent. of the amount
claimed.--(_From Reports A. M. A. Chemical Laboratory, 1916, p. 106._)
“AMBRINE” AND PARAFFIN FILMS[F]
Paul Nicholas Leech, Ph.D.
[F] Contribution from the Chemical Laboratory of the American Medical
Association.
In the last year or so, the hot-wax or paraffin treatment of burns has
been widely discussed both in medical and lay periodicals. Although the
treatment is simply a modification of the well-known use of oil and
ointments, it has received unusual attention, owing to the widespread
sensationalism following the exploitation in France of a secret and
therefore mysterious mixture, “Ambrine,” the formula of Dr. Barthe de
Sandfort. Owing to this publicity, it seemed desirable to investigate
the chemical composition, and to compare its physical properties with
other waxlike substances.
“Ambrine” is promoted as a dressing for burns, frostbites, neuritis,
varicose ulcers, phlebitis, neuralgia, rheumatism, sciatica, gout, etc.
It is a smoky-appearing substance, resembling paraffin in consistency
and without odor. For application, “Ambrine” is melted and applied to
the wound either with a brush or with a specially devised atomizer. It
cools quickly, and leaves a solid, protecting film.
[Illustration:
+ - - - - - - - - - - - - - - - - - +
| _HYPERTHERMALITY A REALITY._ |
| |
| Hyperthermality is a fact, however, through the |
| agency of a keri-resinous product which has been |
| used in France since 1900 under the name of |
| L’Ambrine. Hyperthermine, as the remedial agent |
| will be known in this country, is a combination |
| of several kinds of waxes and resins, scientific- |
| ally blended and containing no medicinal elements |
| whatever. It comes in the form of waxy flakes. It |
| melts at 124° and on cooling resembles a dark |
| colored wax. |
| |
| Hyperthermine is the discovery of Dr. Barthe de |
| Sandfort, an eminent retired French naval surgeon |
| and a member of numerous foreign medical societies. |
| He |
+ - - - - - - - - - - - - - - - - - +
“Ambrine” has been exploited in the United States for some time.
To physicians it was sold under the name “Hyperthermine.” Above is
a photographic reproduction (reduced) of a portion of a booklet
describing “Hyperthermine,” which has been in The Journal office for
some years.]
[Illustration:
+ - - - - - - - - - - - - - - - - - +
| _HYPERTHERMINE’S FIELD._ |
| |
| Hyperthermine can be used in practically all in- |
| flammatory conditions. During the past ten years, |
| under the name of L’Ambrine, our product has been |
| widely used in the hospitals in France, as well as |
| in private practice, and we have very many clinical |
| reports on a variety of subjects. Its greatest use |
| has been in such conditions as sciatica, lumbago, |
| articular and muscular rheumatism, gout, arthritis, |
| burns of all degrees, pneumonia, bronchitis, orchit-|
| is, buboes, soft chancres, peritonitis, dysmenor- |
| rhea, adenitis, mastitis, periostitis, synovitis, |
| conjunctivitis, iritis, irido-choroiditis, abscess- |
| es, bruises, furuncles, whitlow, paronychia, car- |
| buncles, moist eczema and similar dermatological |
| affections, and varicose and tubercular ulcers. |
+ - - - - - - - - - - - - - - - - - +
Photographic reproduction (reduced) from the “Hyperthermine”
(“Ambrine”) booklet recommending it for use in rheumatism, gout,
pneumonia, buboes, dysmenorrhea, eczema, tuberculous ulcers, etc.]
It is said that de Sandfort “stumbled on this treatment by
accident.”[165] Being a sufferer from rheumatism, he had been benefited
by hot mud baths; on returning home he sought a substitute, and finally
made a mixture of paraffin, oil of amber and amber resin. This was
applied hot, serving as a firm poultice. “Years later, he went on
service to a railway in China and was in Yunnan at the time of the
incendiary insurrection, and many badly burned Chinese were brought
in for treatment. Remembering that Ambroise Paré treated such cases
with hot oil, he tried the effect of covering the burn with his melted
ambrine, which at once glazes over, forming a coat impervious to the
air, and his patients ceased to suffer.”[166]
[165] The Outlook, Jan. 17, 1917, p. 100.
[166] Med. Rec., New York, Jan. 27, 1917, p. 160.
“Ambrine” has been sold in America under two names: “Hyperthermine,” as
exploited to physicians, and “Thermozine,” as advertised to the public.
Physical comparison alone shows that Ambrine as now sold differs
from “Hyperthermine” of a few years ago; the probable reason is that
“Ambrine” has changed its formula. This is borne out by Matas,[167]
who states that de Sandfort “admitted that Ambrine was a compound of
paraffin, oil of sesame and resins, but was not at liberty to divulge
its exact composition, as the formula and manufacture of this substance
was now the property of a private corporation, which was exploiting it
as a proprietary and secret remedy.” The later formula differs from the
original.
[167] Matas, Rudolph: Burns Treated with Paraffin Mixtures, New Orleans
Med. and Surg. Jour., April, 1917, p. 681.
Besides the foregoing paraffin preparations, two others have recently
been placed on the American market, “Parresine” (nonsecret) and
“Mulene” (secret).
ANALYSIS OF AMBRINE
“Ambrine” comes in rectangular cakes, about 1-1/2 inches wide, 6
inches long and 1/2 inch thick. It is moderately soft, but somewhat
brittle at ordinary room temperature. A black substance is present,
which evidently settles out during the compounding, as in one side of
the cake these particles can be clearly discerned by holding it up to
the light; in the other side there are no suspended particles. When
melted, the solution is not clear, and a sediment forms. The melting
point (U. S. P. method; see later) is 48.4 C. The plasticity and
ductility[168] are 27 and 30.5, respectively. It is pliable and strong
at body temperature. The saponification number and acid number are both
very low, but a fatty oil is present. Tests indicated oil of sesame.
Ninety-eight per cent. of “Ambrine” is soluble in ether; this soluble
portion may be treated with low-boiling ligroin (petroleum ether), out
of which, on standing, a black asphalt-like substance separates. Of the
ether-insoluble substance, 65 per cent. is soluble in chloroform. The
remaining insoluble substance contains a small amount of silica and
vegetable fiber. The paraffin obtained from “Ambrine” melted at 48.6 C.
As a result of various experiments, it appears that the composition of
“Ambrine” is essentially as follows:
Paraffin (M. P. 48.6 C.) 97.0 per cent.
Fatty oil (sesame?) 1.5 per cent.
Asphalt-like body 0.5 per cent.
Coloring matter, and undetermined 1.0 per cent.
-----
100.0
[168] These determinations will be described later.
OTHER PROPRIETARY FILMS
A cursory examination of “Mulene,” manufactured by the Mulene Company,
Pittsburgh, was also made. This appears to contain paraffin, beeswax, a
fat-soluble red dye and considerable rosin. When heated carefully in a
beaker, the rosin “sticks” to the bottom, and does not go into solution
readily.[169]
[169] When the sample was first obtained, this feature was not observed.
“Paresine,”[170] according to the manufactures, is a mixture composed
of paraffin, 94 to 96 per cent.; gum elemi, 0.20 to 0.25 per cent.;
Japan wax, 0.40 to 0.50 per cent.; asphalt, 0.20 to 0.25 per cent.,
and eucalyptol, 2 per cent., the whole being colored with alkannin and
gentian violet.[171]
[170] Made by the Abbott Laboratories, Chicago, and accepted by the
Council on Pharmacy and Chemistry for New and Nonofficial Remedies, The
Journal, May 12, 1917, p. 1406.
[171] No chemical examination was made.
FORMULA FOR PARAFFIN FILM
In a recent article, Sollmann[172] presented various suggestions for
the compounding of paraffin films. Some of the formulas were promising
and others were not, but all were simple. He did not try to imitate
“Ambrine.” Lieut.-Col. A. J. Hull[173] of the Royal Army Medical Corps,
after experimenting with different combinations, concluded that a
mixture of “1 part resorcin, 2 parts eucalyptus oil, 5 parts olive oil,
25 parts soft paraffin [petrolatum][174] and 67 parts hard paraffin”
served the purpose as well as “Ambrine.” The following formula, which
might be called Asphalt-Paraffin No. 21, much more closely resembles
“Ambrine,” and it seems to have certain advantages, due to the use of a
more suitable grade of paraffin:
Paraffin[175] (M. P. by U. S. P. method 47.2 C.) 97.5 gm.
Asphalt from 3 to 5 drops
Olive oil 1.5 c.c.
[172] Sollmann, Torald: Suggested Formulas for Paraffin Films, The
Journal A. M. A., April 7, 1917, p. 1037.
[173] Hull, A. J.: The Treatment of Burns by Paraffin, Brit Med. Jour.,
Jan. 13, 1917, p. 37; The Treatment of Burns by Paraffin, Therapeutics,
The Journal A. M. A., Feb. 3, 1917, p. 373.
[174] The “soft paraffin” of the British Pharmacopeia resembles
petrolatum, U. S. P., Queries and Minor Notes, The Journal A. M. A.,
April 28, 1917, p. 1281.
[175] The paraffin used in this formula was supplied by the Standard
Oil Company of Indiana; the melting point given by the manufacturers is
from 120 to 122 F., which, according to the American Standard of taking
melting points, gives higher results than the method described in the
pharmacopeia.
[Illustration:
+ - - - - - - - - - - - - - - - - - +
| inception. |
| |
| Where the Dry Wax Poultice has been used |
| |
| Thermozine known in France as l’Ambrine, has been |
| used in the following Parisian hospitals, with |
| 92% of cures: |
| |
| Hospital de la Pitie, services of Drs. Lion, Darier |
+ - - - - - - - - - - - - - - - - - +
Photographic reproduction from a booklet on “Thermozine” showing that
it is identical with “Ambrine.”]
About 10 c.c. of “asphalt varnish” (B. Asphaltum)[176] is placed in
a beaker and heated on the steam bath for one-half hour. From 3 to 5
drops, delivered from a 1 c.c. pipet, are then placed in a casserole,
and 1.5 c.c. of olive oil added. The mixture is heated and stirred
for a few minutes until perfect solution is effected. To this is then
added, with stirring, the paraffin, which has been previously melted.
When it is cooled, a brown solid is obtained.[177] The physical factors
of this paraffin mixture are, melting point 45.4 C. (U. S. P. method);
plasticity, 28.5; ductility, 29; it is very pliable and strong at
38 C., and adheres exceedingly well to the skin, although it detaches
easily. This mixture, which is easy to prepare, is inexpensive, the
cost of the materials being approximately 10 cents a pound.
[176] The “Asphalt Varnish” used was obtained from Remien & Kuhnert
Company, Chicago.
[177] While needless, a color resembling “Ambrine” may be obtained by
the addition of coloring agents.
Both Hull and Sollmann noticed that tarlike substances and melted
paraffin do not mix well. This is noticeable in “Ambrine,” which cannot
be called an “elegant” preparation. The difficulty may be overcome by
first mixing hot olive oil and asphalt; the asphalt will then go into
solution. It is interesting to note that the suggested formula (as well
as others which were also prepared) is not as plastic as the paraffin
itself.[178] This is also true of “Ambrine.” On the other hand, the
melting point of the paraffin is higher. _The important point, however,
in compounding all paraffin preparations, is to select a proper grade
of paraffin as elaborated below._
[178] In a personal communication Dr. Sollmann expressed the opinion
that the synthetic preparation is inferior to the paraffin used in the
formula, basing the view on the greater plasticity of the paraffin.
For practical purposes, the paraffin will most probably serve as well
as the mixture, especially when it is held in place by bandages, but I
believe that the mixture is more adhesive.
EXAMINATION OF PARAFFINS AND PARAFFIN PREPARATIONS
[Illustration: Photographic reproduction (greatly reduced) of a full
page magazine advertisement of “Thermozine,” the name under which
“Ambrine” was sold to the public.]
The name “paraffin” generally applies to a colorless and tasteless
waxlike substance that is solid at ordinary temperature. It is composed
of saturated hydrocarbons, that is, they are unable to take up any more
hydrogen, and thereby are quite stable; the hydrocarbons in paraffin
have the general formula of C↓{n}H↓{2n+2}, ranging as high as C₂₄H₅₀ to
C₂₇H₅₆. Paraffin may be found in crude form in coal, from which source
the first paraffin candles were made. It may be produced from the
distillation of brown coal, as in Germany, or from bituminous shale.
In America, it is obtained chiefly from the distillation of crude
petroleum, being in the residue after the distillation of such products
as naphtha (gasoline), kerosene and the lubricating oils. The residue
is treated by one of a number of processes causing the unpurified
solid paraffin to be made available. The crude paraffin is either
sold as such, or is refined. Paraffin or “paraffin waxes”[179] are
designated in the trade by their melting points (which in the “American
standard” is expressed in Fahrenheit degrees), and as to their state
of refinement as “crude,” “semirefined” and “fully refined” paraffin.
There are certain chemical and physical differences so that two refined
waxes having the same melting point would not have the same plasticity.
The higher melting point varieties of paraffin are hard and tough at
room temperature: when melted, paraffin expands and forms a thin mobile
liquid.
[179] Paraffin is sometimes spoken of as “white wax.” This is
unfortunate, as “white wax” is an official name for “White Beeswax,
U. S. P.” The term “white wax” is also often applied to “Chinese wax,”
which is formed from an insect living on the tree Ligustrum lucidum.
[Illustration: Photographic reproduction from a booklet on “Thermozine”
giving the conditions in which the stuff was alleged to be “very
useful.”]
The significant requirements of paraffin for surgical dressings are
that it should be solid at body temperature, at the same time having
flexibility and adhesiveness, together with a certain amount of
strength. A number of brands of paraffin are sold in the United States,
so that it seemed advisable to examine some of them and compare them
with certain paraffin-film preparations. They were tested as to their
melting points, plasticity, ductility, strength of film, etc.
_Melting Point Determination._--The melting point was determined by
the method of the U. S. Pharmacopeia IX, p. 596. The melting point
as obtained by this method is lower than the melting point used by
manufacturers of paraffin (after conversion to Fahrenheit).
_Pliability and Ductility, Limit Temperature._[180]--A little of the
melted wax was poured from a teaspoon on the surface of the water at
about 40 C., in a tin pan (bread mold). This formed a fairly thin film.
The temperature of the water was then lowered by the addition of cold
water. At each temperature the pliability and ductility were tested
thus:
[180] I am indebted to Dr. Torald Sollmann for these methods.
_Pliability Test._--The film, immersed in water, was doubled on itself,
note being taken whether or not it broke.
_Ductility Test._--The film was pulled under water, note being taken
whether it stretched on being pulled and broke with a ragged fracture;
or whether it broke sharp without stretching. It is desirable that
the pliability and ductility be preserved at as low a temperature as
possible.
_Cotton Films, Adhesives and Detachability._[180]--The melted wax was
applied as it would be for burns; namely, a thin layer was painted on
the inner surface of the forearm with a camel’s hair brush,[181] a
transverse strip about an inch wide being made. This was covered with
a very thin layer of absorbent cotton, and over this another layer of
melted wax was painted. As soon as this had cooled a little, it was
covered by a few layers of bandage and left on for at least an hour. At
the end of that time, the bandage was removed. The cotton film should
be found at the place at which it was applied, showing that it is
sufficiently adherent. It should detach without “pulling” the skin.
[181] When painting a surface with a paraffin film, I found that the
temperature of the paraffin should not be too close to the melting
point, but several degrees above; otherwise it does not “set” well.
[Illustration: Photographic reproduction (greatly reduced) of the
carton in which “Ambrine” is now sold.]
The results of these tests are given in the accompanying table. It can
be seen that nearly all the paraffins examined have properties which
would make them useful, the notable exceptions being Nos. 8, 15 and
16. The more satisfactory products would be those having a melting
point about 47 C., ductility of 30 or below, and plasticity of 28 or
below. The paraffin described in the U. S. Pharmacopeia is not so
satisfactory, the required melting point being between 50 and 57 C.
The use of paraffin bandages has been suggested by Fisher[182] and
Sollmann.[183] In such cases, it may very likely be that a paraffin of
higher melting point would be more satisfactory, owing to its greater
resistance and tougher fiber.
[182] Fisher, H. E.: Nonadhering Surgical Gauze, The Journal A. M. A.,
March 25, 1916, p. 939.
[183] Sollmann, Torald: Paraffin-Covered Bandages, The Journal
A. M. A., April 21, 1917, p. 1178.
SUMMARY
1. “Ambrine” is essentially paraffin in which a small amount of fatty
and asphalt-like body is incorporated; like most secret mixtures, its
composition varies.
2. A simple formula for a paraffin film, similar in chemical
composition but superior in physical properties to “Ambrine,” is that
described as Formula 21. The superiority is due to using a grade of
paraffin that is better adapted to the purpose. The cost of materials
is about 10 cents a pound.
3. The properties of the paraffin used for a surgical dressing are
important. A number of different grades have been examined, in order to
determine the ones that appear most promising. Paraffins Nos. 3, 4, 10,
11 and 25 are the best in the table, and surpass “Ambrine” itself.
4. It is exceedingly probable that further experience will show that
for most purposes simple paraffin will serve just as well as the
mixtures--if, indeed, not better.
Addenda
(_Reprinted from the Annual Report of the Chemical Laboratory of The
American Medical Association, Vol. 10 (1917), p. 32_)
Since the foregoing was published, two other products--“Cerelene” and
“Stanolind Surgical Wax”--were submitted to the Council on Pharmacy and
Chemistry for investigation as to their acceptability for inclusion in
New and Nonofficial Remedies. In this connection the Laboratory was
requested to examine them.
“Cerelene” is manufactured by the Holliday Laboratories, Pittsburgh.
According to the manufacturers, “Cerelene” is a compound composed of
84 per cent. paraffin, 15 per cent. myricyl palmitate and 1 per cent.
elemi gum. As ordinarily marketed, “Cerelene” contains the following
materials: To the beeswax is added Oil of Eucalyptus, U. S. P., 2 per
cent., and Betanaphthol, U. S. P., 0.25 per cent. The manufacturer
further states that the myricyl palmitate is a purified form of
beeswax, free from all impurities, acids, etc., which is solely
manufactured by this company and for which patents are pending. The
properties described for “Cerelene” were as follows:
When cold, Cerelene is a solid wax-like cake of a fine yellow
brown color. On exposure to air for long periods, the amber color
darkens to some extent. It is entirely free from solids, odorless
and tasteless; does not separate or change when melted repeatedly,
and cannot in the melted state be separated by fractional
crystallization. It is entirely neutral to indicators being
perfectly free from both acids and bases.
Tests: Melting Point, U. S. P. method, 126 F.
Density, U. S. P. method, 0.907.
Iodin value, 0.5.
Saponification number, 0.9.
“Stanolind Surgical Wax” is manufactured by the Standard Oil Company of
Indiana. In the submission of the product to the Council on Pharmacy
and Chemistry, it was stated that the product was a specially prepared
paraffin “free from dirt or other deleterious matter.... It has
been steamed and resteamed to drive out any free oil and repeatedly
filtered.”
The examination of the foregoing products yielded the figures described
in Table “B.”--(_From The Journal A. M. A., May 19, 1917._)
THE STABILITY OF IODINE OINTMENTS
L. E. Warren, Ph.C., B.S.
In general, the literature on the keeping qualities of iodine ointment,
and on the stability of iodine if mixed with ointment bases, is
confusing. The recorded evidence is often contradictory. The attention
of the writer was brought to this condition by studies of several
proprietary preparations, Iodex,[184] Iod-Izd-Oil,[185] Iocamfen, and
Iocamfen Ointment.[186]
[184] Rep. Chem. Lab., A. M. A., 1915, 8, 89.
[185] Rep. Chem. Lab., A. M. A., 1915, 8, 106.
[186] Rep. Chem. Lab., A. M. A., 1916, 9, 118.
Iodex was sold under the claim that it is
“... an embodiment of vaporized iodine, in an organic base, reduced
and standardized at 5 per cent. by incorporation with a refined
petroleum product.”
The exact composition of Iodex is a trade secret. Analysis showed that
it contains petrolatum-like substances and combined iodine, the latter
probably in combination with oleic acid. Tests for free iodine were
made in five specimens of Iodex. In one of these no free iodine was
present; in the others the merest traces were found.
Two years ago a preparation called “Iod-Izd-Oil” was examined. This was
claimed to contain 2 per cent. of free iodine in liquid petrolatum.
At the time of the examination the age of the preparation was not
known, but it had been obtained just prior to the analysis, and was
thought not to be very old. The analysis showed that it contained but
about 0.43 per cent. of iodine, all of which was in a free state. The
fact that all of the iodine present was in the free state appeared
to indicate that iodine is relatively stable in liquid petrolatum
solutions.
Iocamfen is a liquid composed of iodine, camphor and phenol. It was
claimed to contain 10 per cent. of free iodine. Analysis showed that
it contained 9.3 per cent. of total iodine (of which 7.5 per cent.
was present in an uncombined state), 66.1 per cent. of camphor and
19.7 per cent. of phenol. After storing for several months a second
assay of Iocamfen showed no appreciable loss in iodine content.
This would indicate that iodine is relatively stable in presence
of phenol and camphor, although immediately after mixing there is
some loss of free iodine. The Iocamfen Ointment was supposed to
contain 50 per cent. of Iocamfen (equivalent to 5 per cent. of free
iodine) in a lard-wax-cacaobutter base. The analysis showed that the
ointment contained but 0.4 per cent. of free iodine, the balance
being in combination. From the results of the examination, and from
correspondence with the manufacturers (Schering and Glatz), it became
evident that the only plausible explanation for the loss of free iodine
in the preparation of Iocamfen Ointment from Iocamfen lay in the
combination of the free iodine with the ingredients of the ointment
base. It seems likely that the free iodine originally present in
Iocamfen for the most part had gradually gone into combination with the
fatty substances after the ointment had been prepared.
The literature was then examined to determine the consensus of opinion
concerning the stability of iodine in iodine ointment. In the older
literature the belief that iodine ointment is unstable appears to be
quite general. Such statements as the following are typical:
The ointment should be prepared only when wanted for use, for it
undergoes change if kept, losing its deep, orange-brown color, and
becoming pale upon its surface.[187]
[187] U. S. Disp., ed. 19, p. 1315.
It is better to prepare it only as it is required for use.[188]
[188] Am. Disp., ed. 2, p. 2022.
This ointment must not be dispensed unless it has recently been
prepared.[189]
[189] U. S. Pharmacopeia, IX, p. 481.
In 1909 Lythgoe,[190] of the Massachusetts Board of Health laboratory,
reported an examination of four samples of iodine ointment. Three were
found to be pure, the fourth was low in iodine. Experiments showed
that iodine ointment deteriorates rapidly; consequently, no further
collections of samples were made.
[190] Rep. Mass. Bd. Health, 1909, 41, 477.
In 1912 Pullen[191] reported that he had prepared two specimens of
iodine ointment according to the British Pharmacopeia, one being
from new lard and the other from a specimen of lard at least 2 years
old. Assays for free iodine were carried out immediately after the
preparations were made, and at intervals afterward up to four months.
The following values were found:
[191] Pharm. Jour., 1912, 89, 610.
Sample I Sample II
Ointment from Ointment from
new lard, old lard,
per cent. per cent.
Iodine introduced 4.0 4.0
Iodine found immediately after making 3.95 3.38
Iodine found after twenty-four hours 3.30 3.15
Iodine found on the third day 3.18 2.62
Iodine found on the seventh day 3.15 2.46
Iodine found on the fourteenth day 3.00 2.45
Iodine found after one month 3.00 2.39
Iodine found after two months 2.90 2.31
Iodine found after four months 2.92 2.26
Pullen found that the loss in free iodine could be accounted for by the
iodine which had gone into combination with the fats of the ointment
base.
Pullen also found that if the potassium iodide and glycerin were
omitted in the preparation of the ointment, the loss in free iodine
was very rapid, the preparation containing practically no free iodine
(only 1/20) after a few hours. He concludes that the use of potassium
iodide and glycerin is necessary for the preservation of the ointment.
He obtained specimens of iodine ointment in drug stores, and assayed
them for free iodine. It is to be presumed that the ages of the several
specimens were not known. The results are found in the following table:
Specimen No. 1 2.74 per cent.
Specimen No. 2 2.85 per cent.
Specimen No. 3 2.62 per cent.
Specimen No. 4 2.48 per cent.
Specimen No. 5 2.53 per cent.
Specimen No. 6 2.79 per cent.
Fried[192] prepared iodine ointment according to the U. S. P. VIII
formula, and assayed it at intervals. His results are tabulated
herewith:
[192] Pharm. Jour., 1912, 89, 610.
Per cent.
Iodine introduced 4.00
Iodine found immediately after making 3.89
Iodine found one hour after making 3.51
Iodine found one day after making 3.48
Iodine found five days after making 3.06
Iodine found ten days after making 2.84
Iodine found thirty days after making 2.81
Iodine found ninety days after making 2.81
Iodine found eight months after making 2.81
Iodine ointment has been official in the U. S. Pharmacopeia since 1870.
Briefly, the method now used for making the preparation is as follows:
Four gm. of iodine, 4 gm. of potassium iodide and 12 gm. of
glycerin are weighed into a tared mortar and the mixture triturated
until the iodine and potassium iodide are dissolved and a dark,
reddish-brown, syrupy liquid is produced. Eighty gm. of benzoinated
lard are then added in small portions and with trituration after
each addition. The mass is then triturated until of uniform
consistence.[193]
[193] The time required to complete the process after the initial
portion of lard has been added should be about twenty minutes.
PARAFFINS AND PARAFFIN PREPARATIONS--TABLE A
KEY:
A: Formula
B: Substance
C: Melting Point, U. S. P.
D: Ductility Limit
E: Plasticity Limit
F: (a) Adhesiveness and Detachability (b) Strength of Film at 38 C.
=======================================================================
A B C D E F
1 “Parowax,” 50.8 32.5 29.0 (a) Adheres and
Stand. Oil Co. of Ind. detaches well;
rather hard
(b) Pliable and
strong
3 “Paraffin 118-120 F.,” 46.8 28.5 24.5 (a) Does not adhere
Stand. Oil Co. of Ind. well; detaches
easily
(b) Pliable but not
strong
4 “Paraffin 120-122 F.,” 47.2 29.0 24.5 (a) Adheres well;
Stand. Oil Co. of Ind. detaches well
(b) Pliable and
fairly strong
5 “Paraffin 123-125 F.,” 48.8 31.5 28.5 Same as 4
Stand. Oil Co. of Ind.
6 “Paraffin 128-130 F.,” 52.0 33.0 30.0 (a) Adheres well;
Stand. Oil Co. of Ind. detaches not so
easily
(b) Pliable and
strong
7 “Texwax,” Texas Co., 51.2 32.5 29.8 Same as 6
Port Arthur, Texas
8 “Paraffin Wax 122-124 F.,” 50.6 36.0 34-35 (a) Unsatisfactory;
Warren Refining Co., does not adhere
Warren, Pa. (b) Only slightly
pliable;
too tough
9 “Paraffin No. 910,” 47.0 30.5 26-27 (a) Adheres well;
Waverly Oil Works, detaches well
Pittsburgh (b) Pliable and
strong
10 “Paraffin No. 920,” 44.4 27.5 25.0 (a) Adheres well;
Waverly Oil Works, detaches well
Pittsburgh (b) Pliable and
fairly strong
11 “Hard Paraffin,” 48.0 28.5 24.5-25.5 (a) Adheres well;
Rob’t Stevenson & Co., detaches well
Chicago (b) Pliable and
strong
12 “Paraffin,” 47.2 33.0 32.5 Not quite as good
Island Petroleum Co., as 11
Chicago
13 “Paraffin 122 F.,” 46.8 30.5 27.5-28 (a) Does not adhere
Gulf Refining Co., so well;
Pittsburgh detaches well
(b) Very pliable
14 “Paraffin 125 F.,” 50.0 32.0 31.0 About as 13
Gulf Refining Co.,
Pittsburgh
15 “Paraffin 132 F.,” 54.8 35.5 34.0 (a) Does not adhere
Gulf Refining Co., well
Pittsburgh (b) Not very pliable,
but strong
16 “Paraffin No. 301,” 50.2 33.0 32-32.5 (a) Does not adhere
National Refining Co., well
Cleveland (b) Not very pliable
18 Paraffin recovered 48.6 30.5 28-28.5 (a) Adheres well;
from “Ambrine” detaches well
(b) Pliable but not
strong
19 “Hyperthermine” 49.4 33.5 30.5-31 (a) Does not adhere
well;
detaches well
(b) Very pliable and
strong
20 “Ambrine” 48.4 30.5 27.0 (a) Adheres well;
detaches well
(b) Very pliable and
strong
21 Paraffin 120-122 F. 45.4 29.0 28.5 (a) Adheres
(see 3), 97.5; excellently;
olive oil, 1.5; detaches well
asphalt, 4 drops (b) Very pliable and
strong
22 “Parowax” (see 1), 97.5; 49.2 32.0 30.5 (a) Adheres well;
olive oil, 1.5; detaches well
asphalt, 4 drops (b) Pliable and
strong
23 “Mulene” 51.0 36.0 28.0 (a) Adheres but
detaches with
difficulty
(b) Pliable but not
strong
24 “Parresine,” 46.0 29.5 26.0 (a) Adheres well;
Abbott Laboratories, detaches easily
(b) Pliable and
fairly strong
25 “Paraffin 118-121 F.,” 45.8 26.4 23.2 (a) Adheres well;
The Atlantic Refining detaches easily
Co., Philadelphia (b) Pliable and
Chicago fairly strong
TABLE B
26 “Cerelene,” 50.0 30.5 26.5 (a) Adheres well;
Holliday Lab.,* detaches with
Pittsburgh pulling
(b) Not strong at
38 C.
27 “Stanolind” Surgical 47.0 28.8 25.0 (a) Adheres well;
Wax,† Standard detaches easily
Oil Co. of Ind. (b) Fairly strong at
38 C.
* On being heated, it readily loses eucalyptol, and a small amount
of resinous substance forms in the bottom of the beaker. If
“Cerelene” is heated to 145 C. and cooled, the resulting product no
longer has the properties of the original “Cerelene.”
† Accepted by the Council on Pharmacy and Chemistry for inclusion
in New and Nonofficial Remedies.
Iodine ointment is officialized also in several foreign pharmacopeias,
although the iodine strength of the several preparations is not
uniform. The formula in the British Pharmacopeia is exactly like that
in the U. S. Pharmacopeia except that pure lard is directed to be used
instead of benzoinated lard. Some of the foreign pharmacopeias also
specify that the preparation must be freshly prepared when wanted. In
the earlier editions the U. S. Pharmacopeia directed the ointment to
be prepared by using water as the solvent for the potassium iodide. In
the U. S. Pharmacopeia VIII the formula was changed so as to employ
glycerin, and that solvent is now official. Water is still prescribed
as the potassium iodide solvent by the Pharmacopeias of the Netherlands
and of France.
From the examination of the literature it seems probable that iodine
ointments which contain petrolatum products only as the ointment bases
are apt to be relatively stable, so far as the content of free iodine
is concerned. On the other hand, ointments the bases of which contain
fats of the unsaturated fatty acid series, such as oleic acid, do not
satisfactorily preserve the iodine in the free state. In the latter
class it seems likely that the iodine enters into combination with
the unsaturated fatty acids. Accordingly, on theoretical grounds,
an ointment base composed of pure stearin (if such substance were
available) but softened by an admixture of liquid petrolatum would
preserve the iodine satisfactorily. Cocoanut oil (iodine No. 8) ought
to be suitable also if mixed with hard paraffin.
Since the literature was not sufficiently concordant to warrant
positive conclusions concerning the stability of ointments containing
free iodine, it seemed worth while to conduct experiments with
preparations of known origin. Accordingly, a number of preparations
containing free iodine were made under varying conditions and each was
assayed for its free iodine content immediately after its manufacture
and from time to time later.
Leaf lard of the best quality obtainable was purchased from a butcher.
This was rendered in an open dish on the steam bath. The preparation
was of a fine color, and uniform consistence and had a faint but
not unpleasant odor. Two specimens of lard were furnished by the
research department of Armour and Company. An effort was made to
procure specimens of lard having iodine absorption numbers as far
apart as possible, _i. e._, one with a low and the other with a high
iodine value. This was done in order to determine whether the keeping
qualities of the ointments prepared from the two would be alike.
One of the specimens (_a_) was described as
“Natural lard; iodine value, 57.1. Leaf lard used exclusively for
butterine and benzoinated lard.”
The other specimen was described as
“Prime steam lard. Good, commercial grade of lard for general use;
iodine value, 69.0.”
The iodine absorption numbers of the three specimens were determined by
the U. S. P. process to be as follows:
Laboratory rendered specimen 57.1
Armour specimen (_a_) 57.65
Armour specimen (_b_) 67.55
Each specimen was benzoinated according to the process described in
the U. S. P. IX and 100 gm. of iodine ointment were prepared from each
according to the U. S. P. process. Another specimen was made from
benzoinated lard and iodine only[194] without the addition of either
glycerin or potassium iodide. This was made to contain 4 per cent. of
iodine.
[194] In order to facilitate the incorporation of the iodine with the
fatty base the iodine was first powdered by trituration with alcohol
and drying the powder in the air.
Immediately after preparation each of these iodine ointments was
assayed for free iodine, and each was reassayed at intervals later.
The method for the determination of iodine in the ointment was that
employed in this laboratory for the determination of iodine in Iocamfen
Ointment.[195] It is essentially the same as was employed by Pullen
for the determination of uncombined iodine in iodine ointment.[196] As
carried out in this laboratory for iodine ointment it is as follows:
[195] Rep. Chem. Lab., A. M. A., 1916, 9, 118.
[196] Pharm. Jour., 1912, 89, 610.
From 5 to 8 gm. of the ointment were weighed in a small porcelain
capsule, the capsule and contents placed in a 16 oz. salt mouth
bottle together with 20 c.c. of chloroform, 10 c.c. of potassium
iodide solution and 40 c.c. of water. Tenth-normal sodium
thiosulphate was slowly added with agitation until the pink color
of the chloroform layer had nearly disappeared. A little soluble
starch was then added and the titration continued until a blue
color in the aqueous layer could no longer be obtained by repeated
shaking.
The findings for the several assays are tabulated herewith:
U. S. P. U. S. P. U. S. P. Ointment
Ointment Ointment Ointment from
Age at from from from lard and
time laboratory commercial commercial iodine only
of rendered lard lard (laboratory
assay lard Grade I Grade II rendered lard)
(% I) (% I) (% I) (% I)
Freshly made 3.32 3.26 3.30 0.32
After 3 days 3.25 .... .... 0.23
After 7 days 2.99 3.17 3.15 ....
After 3 weeks 3.01 3.19 3.07 ....
After 7 weeks 3.12* 3.10 3.02 ....
After 3 months 2.98 2.88 2.88 ....
* This slight rise in iodine content followed by a fall could not
be accounted for. The specimen was believed to have been very
thoroughly mixed at the time of manufacture.
That the fatty constituents of the ointment contained iodine after the
preparation had been made for some time was demonstrated. Some of the
material was examined as follows:
A portion of the ointment which had been made for nearly three
months was shaken in a separator with chloroform and a dilute
mixture of potassium iodide and sodium thiosulphate solutions.
After all of the free iodine had been removed the chloroformic
solution of the fats was washed several times with a very dilute
solution of sodium thiosulphate. The chloroformic solution was
filtered, evaporated and the residue dried over sulphuric acid.[197]
[197] The resultant fatty residue was of a brownish-green color. It
no longer had either the taste, color or odor of lard. It was noted
that the fats, after removal by this method from the freshly prepared
ointment, were nearly white. As the ointment aged the fat became
successively darker in color.
The separated fat was then tested for iodine by Kendall’s method.[198]
It was found to contain iodine in considerable amounts, but
quantitative determinations were not made.
[198] The method depends upon the conversion of all of the iodine
compounds into iodate by fusion with sodium hydroxide and oxidation
with potassium nitrate. The melt is dissolved in water, a little sodium
bisulphite added, the solution cooled and neutralized with phosphoric
acid, using methyl orange as indicator. An excess of bromine water
is added, and the mixture boiled to expel carbon dioxid and bromine.
A little sodium salicylate is added, the solution cooled, an excess
of potassium iodid added, and the liberated iodine titrated with
tenth-normal sodium thiosulphate in the usual way. One sixth of the
iodine found is obtained from the material assayed, the balance being
furnished by the potassium iodide added.--_Jour. Biochem._, 1914, 19,
251.
The Pharmacopeia of the Netherlands directs that iodine ointment shall
contain 3 per cent. of potassium iodide and 2 per cent. of iodine
instead of equal proportions (4 per cent. of each) as prescribed by
the U. S. Pharmacopeia. Likewise the French Pharmacopeia directs that
10 per cent. of potassium iodide and only 2 per cent. of iodine shall
be used. Both of these pharmacopeias use water instead of glycerin as
the solvent. Loose combinations of iodine and potassium iodide, such
as are represented by the compound having the formula KI₃, have been
described. The quantity of potassium iodide prescribed by the U. S.
Pharmacopeia for the preparation of iodine ointment is not sufficient
to form such a compound as KI₃ with all of the iodine directed to
be used. Since some of the pharmacopeias use larger proportions of
potassium iodide (more than sufficient to form the compound, KI₃),
it seemed worth while to determine whether an ointment containing
a greater proportion of potassium iodide than that required by the
U. S. Pharmacopeia would be more stable than the official article.
Accordingly a specimen was prepared to contain 4 per cent. of iodine, 8
per cent. of potassium iodide (twice the U. S. P. requirement), 12 per
cent. of glycerin and 76 per cent. of lard. This was assayed for its
free iodine content immediately after preparation, and found to contain
3.68 per cent. Nine days later it contained 3.70 per cent. Another
specimen of the same iodine strength prepared from grade No. 2 of
commercial lard assayed 3.69 per cent. at the initial assay, and seven
days later 3.40 per cent. From these experiments it seems likely that
the free iodine content of the U. S. Pharmacopeia iodine ointment could
be raised somewhat by increasing the proportion of potassium iodide.
The results of these studies confirm the findings of Pullen and of
Fried in all essential particulars. It appears that during the process
of manufacture of iodine ointment about 20 per cent. of the free iodine
goes into combination with the fatty constituents of the ointment.
On standing for a month approximately an additional 5 per cent. goes
into combination, after which there is practically no loss in free
iodine content. In other words iodine ointment which is a month old
is a relatively stable preparation. It appears to make no noticeable
difference upon the rate and amount of iodine absorption whether
the lard from which the ointment is made has a high or a low iodine
absorption value. The composition of iodine ointment, which has been
made sufficiently long to have reached equilibrium, is approximately as
follows:
Free iodine 3 per cent.
Iodine combined with fat 1 per cent.
Potassium iodide 4 per cent.
Benzoinated lard (containing iodine) 80 per cent.
The U. S. Pharmacopeia requirement that iodine ointment shall be
freshly prepared when wanted appears to be unnecessary. Probably most
pharmaceutical manufacturers are aware of this, for many of them
include the preparation in their trade lists. The presence of an iodide
appears to be necessary, to prevent practically all of the iodine from
entering into combination with the fat.[199]--(_From the American
Journal of Pharmacy, August, 1917._)
[199] In order to determine whether the iodine which is in combination
with fat is absorbed through the skin, a few experiments were carried
out. The dark-colored iodine-containing fat (obtained from the ointment
and washed free from potassium iodide by the method described above)
was rubbed thoroughly into the skin of the forearm. It was allowed to
remain for four hours, after which the limb was scoured with soap suds.
Beginning at the time of the application the urine was collected for
forty-eight hours. This was evaporated to small bulk and the residue
tested for iodine by Kendall’s method. Small amounts of iodine were
found. These findings were taken to indicate that the iodine-containing
fat is absorbed to some extent by the skin. It is generally believed
that potassium iodide is not absorbed by the unbroken skin. Therefore
it seems reasonable to suppose that the principal iodine effects
obtainable from iodine ointment are those due to the free iodine
contained in the preparation, supplemented to a slight extent by
the iodine which is contained in the fatty ointment base.--_Jour.
Biochem._, 1914, 19, 251.
IODOLENE AND THE SOLUBILITY OF IODIN IN LIQUID PETROLATUM
The Council on Pharmacy and Chemistry was asked to examine a
preparation submitted with the statement that it was “iodin crystals
incorporated in a petroleum product.” The name “Iodolene” was proposed
by the promoters, providing the product was found eligible for New and
Nonofficial Remedies.
Iodolene was stated to have been prepared by treating a liquid
petrolatum, obtained from Gulf Coast petroleum, with an excess of
iodin; the mixture was subsequently “placed in an oven for three
hours.” The claim was made that this method of procedure produced a
preparation containing more iodin than market specimens which had been
examined, namely: “over 1.50 per cent. free iodine.”
Two specimens of the product were submitted, one stated to have been
unfiltered, and the other filtered. Both of the specimens emitted a
strong odor of hydrogen sulphide upon removing the stopper from the
respective containers.
_Iodin Content of Iodolene._--The iodin content of the filtered
specimen was determined thus: A weighed amount--3 to 5 gm.--was
transferred to a separator by means of 20 c.c. of ligroin, used in
portions. Twenty c.c. of 10 per cent. potassium iodid solution was
added and the free iodin titrated with tenth-normal sodium thiosulphate
solution (with agitation), the end point being the absence of a yellow
color in the _aqueous_ layer. The amount of free iodin was found to be
1.32 per cent.
_The Solubility of Iodin in Liquid Petrolatum._--To determine
the solubility of iodin in Liquid Petrolatum, 200 c.c. of Liquid
Petrolatum-Squibb (said to be composed of hydrocarbons of the naphthene
series) and 200 c.c. of Stanolind Liquid Paraffin (said to be composed
chiefly of marsh gas hydrocarbons) were each treated with 5 gm. of
iodin crystals. The two mixtures were maintained for a week at a
temperature somewhat above that of the room and agitated occasionally.
Each was then cooled to room temperature (about 22 C.), agitated for
a day and then filtered. The amount of iodin in the preparation made
with Liquid Petrolatum-Squibb was found to be 1.42 per cent. The iodin
content of the preparation made with Stanolind Liquid Paraffin was 1.30
per cent.
In view of these findings the prospective manufacturer was advised that
the Council cannot countenance a proprietary name for an unofficial,
simple solution of iodin in liquid petrolatum.--(_From Reports A. M. A.
Chemical Laboratory, 1917, p. 87._)
AMERICAN-MADE SYNTHETIC DRUGS--I
Examination of American-Made Acetylsalicylic Acid
Paul Nicholas Leech, Ph.D.
At the request of the Council on Pharmacy and Chemistry, the A. M. A.
Chemical Laboratory has undertaken examinations of American-made
synthetic drugs. The most extensively used synthetic is acetylsalicylic
acid and hence an investigation of this product was deemed expedient.
For seventeen years acetylsalicylic acid was protected by a United
States Patent (the proprietors were not given a patent in other
countries) and sold under the name “Aspirin.” In February, 1917, the
patent expired, and since then a number of firms have engaged in the
manufacture of acetylsalicylic acid, selling it either as such or
as aspirin, modified, of course, by a distinctive firm designation.
During this period the former manufacturers (The Bayer Co., New York,
in past years called Farbenfabriken of Elberfeld Co., New York) have
been extensively advertising, both to physicians and the public, the
alleged superior qualities of their product. The chemical examination,
therefore, was concerned chiefly with tests of purity, and the
comparison of the American brands with the formerly patented product.
In European countries, acetylsalicylic acid[200] is described in the
various pharmacopeias as a condensation product of acetic anhydride
or acetyl chloride with salicylic acid (_o_-hydroxybenzoic acid).
Generally the test of identification is hydrolysis of acetylsalicylic
acid and qualitative tests for acetic acid and salicylic acid. For
purposes of purity the requirements are essentially that the specimen
should have a certain melting point, should show absence of salicylic
acid by means of ferric chloride (the manipulations for the tests are
variously described) and leave no appreciable ash. The two tests of
purity most generally employed, however, are the melting point and the
reaction with ferric chloride.
[200] Unfortunately, the nondescriptive name “aspirin” has been used
extensively in European literature and has even got into European
pharmacopeias, instead of the scientific name “acetylsalicylic acid.”
MELTING POINT
The melting point of acetylsalicylic acid has been given at various
temperatures from 118 to 137 C.[201]; the British Pharmacopeia
describes the melting point at 133 to 135 C.; the German Pharmacopeia
“about 135 C.;” the French Pharmacopeia at 135 C.; New and Nonofficial
Remedies, 1917, 134 to 136 C. The Bayer Company, in the patent trial
at Chicago a number of years ago, gave among the “four infallible
tests” a melting point of “about 135 C.” Several men have carefully
determined the melting point in recent years. Emery and Wright[202] in
1912 found that “Aspirin, Bayer” melted at 130.5 to 131 C. In France,
François[203] has determined the melting point of pure acetylsalicylic
acid, which, according to his method, is 132 C. When various samples
of acetylsalicylic acid were examined in this laboratory, it was
found that the melting point of none was as high as that described
in New and Nonofficial Remedies or the British, French, or German
pharmacopeias when taken according to the general method of the U. S.
Pharmacopeia, Vol. 9, p. 596. On critical observation, it may be
seen that the melting point of acetylsalicylic acid is preceded and
accompanied by decomposition. If the sample in the melting tube is
heated from the original room temperature of the bath to 120 C., the
temperature of melting will be lower than if the bath is first heated
to 120 C. and the melting-point tube then placed in the bath.[204]
Thus the melting point of acetylsalicylic acid, like so many organic
compounds which decompose and do not melt sharply, is unsatisfactory
and cannot be taken as an “infallible test” of purity, especially when
determined by different operators who do not give their method in
detail. After making a large number of melting-point determinations
of acetylsalicylic acid, alone and in parallel with other operators,
it was decided to use the method described in the U. S. Pharmacopeia
modified by first heating the bath to 120 C. before attaching the
melting-point tube to the thermometer.
[201] For reference to older literature see Beilstein, II, 1496 (889).
[202] “The Melting Temperature of Aspirin and Salicylic Acid Mixtures,”
_Proc. Assoc. Off. Agr. Chem._, 1912; Bureau of Chemistry, Department
of Agriculture, _Bull._ 162.
[203] “Assay of Aspirin,” _J. Pharm. Chem._, 15 (117), No. 7, 213.
[204] Similar observations were made by Emery and Wright, who state:
“An accurate determination of the melting temperature in this way (the
rate of heating was such as to give a rise in temperature of about 1°
per minute) is rendered difficult by the fact that ‘aspirin’ decomposes
on heating, as evidenced in the depression of the melting temperature
of the pure substance of about 1° for every five minutes’ heating just
below its melting temperature.”
The melting point of purified acetylsalicylic acid was found to be
131.5 to 132.5 C. (corr.).[205] With the exception of one specimen,
which was obviously impure, the various specimens examined melted
between 128 and 133 C. as may be seen in the accompanying table. It
would appear that this range of melting points would be more acceptable
and reliable than the melting points described in various standards.
[205] Isolated crystals attached to the walls of the melting-point
tube, apart from the bulk acetylsalicylic acid, melted at a lower
temperature.
PRESENCE OR ABSENCE OF FREE SALICYLIC ACID
It is generally conceded that the presence of salicylic acid in amounts
more than traces is deleterious. Furthermore, the amount of salicylic
acid is a good index of the purity of the acetylsalicylic acid, because
the test is so delicate that, under favorable conditions, mere traces
may be determined and, as a rule, the better the product, the less the
amount of free salicylic acid.
The tests appearing in various pharmacopeias for salicylic acid as
an impurity in acetylsalicylic acid do not give concordant results,
different workers interpreting the results differently, nor are they
detailed in such a manner as to yield maximum delicacy.
After experimentation, it was decided to establish a “limit” test of
approximately 0.1 per cent. free salicylic acid, when carried out
according to the following method:
0.1 gm. of the substance was placed in a dry colorimeter tube and
1 c.c. of alcohol,[206] previously distilled over NaOH, was added.
After the acetylsalicylic acid had dissolved, 48 c.c. of water and
1 c.c. of fresh 0.1 per cent. ferric chloride (FeCl₃.6H₂O) solution
were added. At the same time a control was run by treating 1 c.c. of
a “standard” salicylate solution the same as above.[207] If within
two minutes the color given by acetylsalicylic acid is not more
intense than the color given by the “standard,” the presence of not
more than 0.1 per cent. free salicylic acid is proved.[208]
[206] An excess of alcohol destroys or lessens the color when only a
very minute amount of salicylic acid is present.
[207] The control should be made each time as standing in the air
changes its tinctorial power.
[208] The presence of pure acetylsalicylic acid does not seem
to affect the iron (Fe+++) salicylic acid coloration. The small
amount of acetic acid was added to the sodium salicylate control
solution (1) to stimulate an acidity approximating the acidity of
the acetylsalicylic acid, and (2) since acetylsalicylic acid gives
by hydrolysis both acetic acid and salicylic acid, it was thought
advisable to add acetic acid to the standard. If there is any free
acetic acid in a sample of acetylsalicylic acid containing salicylic
acid (which I believe is generally the case when salicylic acid is
present) then it would modify the color given by the same amount
of salicylic acid alone. For this reason it was thought to be more
comparable to have the standard contain a slight amount of acetic
acid.
The solutions used were prepared as follows:
Redistilled alcohol was treated with a small amount of sodium
hydroxide for twenty-four hours, then again distilled.
The color standard was made by dissolving 0.116 gm. of dried sodium
salicylate in water, adding 1 minim of glacial acetic acid, and
making up to 1,000 c.c. Each c.c. represents 0.1 mg. of salicylic
acid.[209]
[209] This standard is somewhat similar to the one proposed by T. W.
Thoburn and Paul J. Hanzlik, _J. Biol. Chem._, 23, 175.
The ferric chloride solution was made by diluting 1 c.c. ferric
chloride (FeCl₃.6H₂O) test solution U. S. P. with 99 c.c. of water.
The diluted solution must be freshly prepared each day.
With one exception, all of the commercial specimens examined responded
satisfactorily to the above test showing less than 1 part salicylic
acid in 1,000 parts acetylsalicylic acid. The individual results are
given in the accompanying table.
MELTING POINT AND SALICYLIC ACID DETERMINATIONS
Melting Point Free Salicylic Acid
BRAND Corrected Colorimetrically
Acetylsalicylic acid, 130.0-131.0° Colored, but showing
P. W. R.[1] less than 0.1 per cent.
Acetylsalicylic acid, 130.0-131.0° No color
Millikin[2]
Acetylsalicylic acid, 129.0-130.0° No color
Millikin[2]
5-grain capsules
Acetylsalicylic acid, 128.0-129.0° (_a_) Colored, but showing less
Millikin,[1] than 0.1 per cent. (_a_)
5-grain capsules[3] 125.5-126.5° (_b_) Considerably more than
0.1 per cent. (_b_)
Acetylsalicylic acid, 131.0-132.0° No color
Squibb[2]
Acetylsalicylic acid 131.0-132.0° No color
(Aspirin),[1]
Monsanto
Acetylsalicylic acid, 130.5-131.5° Colored, but showing less
M. C. W.[1] than 0.1 per cent.
Acetylsalicylic acid, 131.5-132.5° Colored, but showing less
M. C. W.[1] than 0.1 per cent.
Acetylsalicylic acid, 131.0-132.0° Colored, but showing less
M. C. W.[1] than 0.1 per cent.
Aspirin, Bayer[1]
(before patent 131.5-132.5° No color
expired)
Aspirin, Bayer[1] [4]
(after patent 128.5-129.5° Colored, but showing less
expired) than 0.1 per cent.
Aspirin, Bayer[1] [4]
(after patent 129.5-130.5° Colored, but showing less
expired) than 0.1 per cent.
Aspirin, Lehn 130.5-131.5° 0.1 per cent.
and Fink[2]
Aspirin, Lehn 130.5-131.5° Colored, but showing less
and Fink[2] than 0.1 per cent.
Aspirin, Lehn 131.0-132.0° Colored, but showing less
and Fink[1] than 0.1 per cent.
[1] Obtained on the open market.
[2] Obtained from manufacturer.
[3] One-third of the capsules (_a_) contained a white powder;
two-thirds of the capsules (_b_) contained a pink powder having
strong odor of acetic acid and not complying with the tests.
[4] Not described in “New and Nonofficial Remedies, 1917”; the
other products are.
OTHER TESTS
New and Nonofficial Remedies, 1917, requires that acetylsalicylic acid
shall form a clear solution with warm sodium carbonate solution; that
sulfates, chlorides and heavy metals shall be absent; that 0.5 gm.
shall leave no weighable ash. All the brands reported in this paper
complied with these requirements.
So far there has been no satisfactory quantitative estimation of
acetylsalicylic acid. True, various methods have been proposed,
but they are objectionable. It was thought that hydrolysis of
acetylsalicylic acid and then titrating the solution by comparing the
color formed by ferric chloride with that of a standard control might
yield interesting results, providing that the conditions were alike.
For this purpose 1 gm. of acetylsalicylic acid was dissolved in 10 c.c.
of alcohol and diluted to 1,000 c.c. The solution was then heated at
98 to 100 C. for two hours, allowing the alcohol to evaporate, then
allowed to stand at room temperature (22 C.) for twenty-two hours.
After adding water sufficient to make 1,000 c.c., it was compared
colorimetrically for salicylic acid strength. The amount of hydrolysis
varied so with different samples under the same conditions, that it
was realized that an approximate assay by this method was unreliable.
If the assay were made under more exact conditions, quantitative
comparisons might be possible. In one experiment, after sixty days the
hydrolysis of the acetylsalicylic acid was 61 per cent., which is in
rough agreement with the work of Tsaklatos and Horsh.[210]
[210] _Apoth. Ztg._, 1915, p. 247; _Bull. soc. chem._, 17 (1915), 401.
“Studies of the decomposition of aspirin determined by titrametric
methods and by conductivity measurements indicate that the reaction is
exceedingly complex,” T. and H. _Chem. Abs._, 10, 591.
DISCUSSION
Apart from the proposed revision of the standards for the melting
point and limit of salicylic acid in acetylsalicylic acid, the
examination shows that there is no appreciable difference between the
various brands of acetylsalicylic acid examined, all of them with one
exception (acetylsalicylic acid, Millikin, 5-grain capsules, purchased
on the open market) complying with the tests described in this paper.
The Journal of the American Medical Association, in past years, has
protested repeatedly against the monopoly given to the Bayer Company
for their “Aspirin,” contending that acetylsalicylic acid (aspirin)
was not new, and that “Aspirin, Bayer” was simply a good brand of
acetylsalicylic acid which could be bought in foreign countries at
much lower prices than here. Although the patent in the United States
has expired, “Aspirin, Bayer” is still being retailed at higher prices
than other products which are now enjoying the privilege of American
manufacture.
Mr. Paul Bakewell,[211] in an opinion answering the warning circular of
the Bayer Co. in reference to the use of the word “aspirin” by firms
other than Bayer, argues very ably that acetylsalicylic acid, before
the patent was granted, meant the impure substance which was not used
therapeutically, while “aspirin” was designated as the improved product
(a new article of manufacture, the particular acetylsalicylic acid made
under the Hoffman patent) and “is the substance now known in pharmacy
as aspirin” (statement made by an officer of the Farbenfabriken of
Elberfeld Co. in U. S. Circuit Court, 1909). The products reported
in this paper are (with the one exception) the same as described in
the Hoffman patent, and, in the sense of Mr. Bakewell’s argument, are
“aspirin.” However, it would seem better if the name acetylsalicylic
acid, instead of aspirin, were used, especially by physicians in
their prescriptions because (1) it is a generic, scientific name; (2)
“Aspirin, Bayer” is sold at higher prices than other products, whereas
chemically equivalent products sold under the descriptive name may be
purchased at a lower price. Finally, the manufacture of acetylsalicylic
acid in this country is another example of the fact that American
chemists can produce the drug synthetics, and at the same time make
products as good as, if not better than, those of German origin.
[211] “In the Matter of Aspirin. Answer to the warning circular of the
Bayer Co. of June 1, 1917,” by Mr. Paul Bakewell, Monsanto Chemical
Works.
I express my appreciation to Dr. W. A. Puckner for his kind
interest.--(_From the Journal of Industrial and Engineering Chemistry,
April, 1918._)
THE STANDARDIZATION OF COMMERCIAL BISMUTH TRIBROMPHENATE
William Rabak, Ph.G., Sc.B.
This work was begun in view of a request received by the Council on
Pharmacy and Chemistry from the Medical Section of the Council of
National Defense for a report on the quality of bismuth tribromphenate,
offered to the government by a certain firm.
In submitting a specimen of its product, “Bismuth Tribromphenolate,”
the firm claimed that “it is of high character, matching exactly the
German product formerly imported into this country,” and expressed the
belief that it would be found to conform to the standards for this
preparation in New and Nonofficial Remedies. Later a second specimen
was received from the same company, with the request that this be
substituted for that first received. It was explained that the first
had been taken from an experimental lot, and that the second, taken
from the regular factory output, was identical with the first except
that it was free from odor because of the more thorough washing to
which it had been subjected. Accordingly, the examination which is
reported below refers to the second specimen only.
New and Nonofficial Remedies, 1918, defines bismuth tribromphenate as
basis bismuth tribromphenate having the formula Bi(C₆H₂Br₃O)₂OH.Bi₂O₃,
and it is required to yield not less than 49.5 per cent. of bismuth
oxid (the chemical formula requires 46.2 per cent. bismuth, or 51.6
per cent. bismuth oxid, Bi₂O₃, and 49.2 per cent. tribromphenate,
C₆H₂Br₃.OH). It describes it as a “fine, yellow, nearly odorless and
tasteless powder, neutral in reaction,” and “only slightly soluble in
water, alcohol, chloroform, liquid petrolatum and vegetable oils.” It
is required to yield tribromphenol (to which a melting point of 95 C.
is assigned) when decomposed by alkali and the alkali tribromphenate
decomposed by acid, the separated tribromphenol purified and dried.
As the New and Nonofficial Remedies description appeared loosely
drawn--it had been based on information furnished for the product
Xeroform when this, because of patent protection, was the only bismuth
tribromphenate on the market--it was decided to include in the
examination also specimens of the two brands of Bismuth Tribromphenate
included in New and Nonofficial Remedies, namely, Bismuth
Tribromphenate-Merck (Merck and Company) and Xeroform-Heyden (The
Heyden Chemical Works). The Merck specimen had been received by the
Council from Merck and Company in 1915, while the Heyden preparation
was obtained direct from the firm’s Chicago branch in April, 1918. At
this time Bismuth Tribromphenate-Merck could not be obtained from the
Chicago wholesale houses.
All three specimens were nearly odorless. Two of the specimens (the
Research Council Specimen and Merck products) were of a lemon-yellow
color, while the Heyden preparation was of a grayish color.
BISMUTH DETERMINATION
Four methods for the determination of the bismuth content of the
specimens were tried:
(_A_). _Direct Ignition to Bismuth Oxid._--This method was abandoned
because of the tendency to ignite suddenly during the incineration and
the consequent loss of material.
(_B_). _The Method of the Japanese Pharmacopeia, Third Revised Edition,
Translated by the Pharmaceutical Society of Japan._--The method
consists in treatment of the product with nitric acid, evaporation and
subsequent heating to bismuth oxid. This method also was abandoned
because of tendency toward sudden ignition with loss of material.
(_C_). _The Method of Kollo (Apotheker Zeitung, 1910, p. 99)._--The
method consists in decomposition of the product by heating on water
bath with normal sodium hydroxid solution, with formation of soluble
sodium tribromphenate and insoluble bismuth hydroxid. The bismuth
hydroxid is collected on a filter, washed with hot water until a few
drops of the filtrate no longer turn litmus paper blue, dried and
heated to constant weight and weighed as bismuth oxid.
(_D_). _A. M. A. Method (Reports A. M. A. Chem. Lab., 1911,
p. 18)._--This method consists in dissolving the product in hot, strong
hydrochloric acid, diluting, filtering and precipitating by saturation
with hydrogen sulphid. The bismuth sulphid obtained is dissolved in
nitric acid and from the solution obtained the bismuth is precipitated
by addition of an excess of ammonium hydroxid and ammonium carbonate.
The precipitate is collected and converted to bismuth oxid by heat.
The following tabulation shows the results obtained by Methods “C” and
“D”:
TABLE 1.--BISMUTH CONTENT OF BISMUTH TRIBROMPHENATE
Gm. of Gm. of Per Cent.
Method Salt Bi₂O₃ of Bi₂O₃
No. 1 Research Council Spec C 2.1312 1.1754 55.1
No. 1 Research Council Spec D 0.5151 0.2772 50.03
No. 2 (Merck & Company) C 2.0287 1.2543 61.8
No. 2 (Merck & Company) D 0.5064 0.2634 52.01
No. 3 (Heyden Chem. Works) C 2.0472 1.6020 78.2
No. 3 (Heyden Chem. Works) D 0.5227 0.3546 67.8
It is seen from the tabulation that the results obtained by the Kollo
method (Method C) are higher than those by the sulphid method (Method
D) and that duplicate determinations show a rather wide variation. The
results by the sulphid method are somewhat lower than those by the
Kollo method, but duplicates agree fairly well. In view of the fact
that the Kollo method will give excessive results if impurities such
as talcum, etc., are present and in consideration of the satisfactory
results obtained in previous work with the sulphid method, the figures
obtained by this method are taken as indicative of the bismuth content
of the specimens examined. Calculating the per cent. of bismuth oxid
obtained to bismuth (Bi), the following values are obtained:
Bismuth Tribromphenolate, Research Council Specimen: Bismuth, 44.8
per cent.
Bismuth Tribromphenate-Merck, Merck & Co.: Bismuth, 46.6 per cent.
Xeroform, Heyden Chemical Works: Bismuth, 60.7 per cent.
TOTAL TRIBROMPHENOL
The content of tribromphenate radical, C₆H₂Br₃O-, was determined by
the method of Kollo (Apotheker Zeitung, 1910, p. 99). It consists in
titrating the filtrate of the bismuth oxid determination of Kollo,
described under “C” (bismuth determinations), with normal hydrochloric
acid, using phenolphthalein as an indicator. The cubic centimeters
of normal alkali consumed multiplied by the theoretical factor 0.331
gives the weight of tribromphenol (combined and free) contained in the
specimen.
The following results were obtained:
TABLE 2.--DETERMINATION OF TOTAL TRIBROMPHENOL IN BISMUTH TRIBROMPHENATE
Gm. Tribromphenol
Gm. of Calculated from Per Cent.
Salt Theoretical of Total
Taken Factor Tribromphenol
No. 1 (Research Council Spec.) 1.7817 1.0592 59.44
No. 2 (Merck & Co.) 0.9743 0.5627 57.75
No. 3 (Heyden Chem. Works) 2.0440 0.4303 21.04
UNCOMBINED TRIBROMPHENOL
The definite chemical formula given in New and Nonofficial Remedies
for bismuth tribromphenate and the statement that it is “only slightly
soluble in ... alcohol ...” requires the absence of uncombined
tribromphenol, but no method for its detection or determination is
provided.
In the U. S. Patent 516,358 (expired March 13, 1911), issued to Bruno
Richard Seifert, assignor to Dr. F. Von Heyden, for “Phenol Bismuth
Compound” the freedom from uncombined tribromphenol was provided for by
the direction to wash with alcohol the product obtained.
In the Swiss Pharmacopeia the permissible content of uncombined
tribromphenol is limited thus:
“If 0.5 gm. be shaken with 5 c.c. of alcohol and 1 c.c. of the
filtrate be diluted with 15 c.c. of water, neither a turbidity nor
a flocculent precipitate should appear....”
When this test was applied to the three specimens under examination,
the Merck and Heyden specimens complied, while the Research Council
specimen did not comply, with this requirement.
_Method 1._--About 1 gm. of bismuth tribromphenate was placed in a
flask, 20 c.c. of 95 per cent. alcohol added and shaken for fifteen
minutes, after which it was filtered by suction through a Gooch filter
into an Erlenmeyer flask. The flask was rinsed with 10 c.c. of alcohol
and finally the filter was washed with 10 c.c. of alcohol, 25 c.c.
of tenth-normal sodium hydroxid solution were added to the alcoholic
filtrate (which was nearly but not perfectly clear) containing the
tribromphenol, and the residual alkali titrated with tenth-normal
hydrochloric acid.
The number of cubic centimeters of tenth-normal alkali consumed
multiplied by 0.331 gave the weight of tribromphenol (Table 3).
TABLE 3.--DETERMINATION OF FREE TRIBROMPHENOL
Gm. Tribromphenol
Calculated from Per Cent.
Gm. of Theoretical Free
Salt Taken Factor Tribromphenol
Research Council Spec. 2.3351 0.3806 16.31
Merck & Co. 0.7980 0.0364 4.56
Heyden Chemical Works 1.9460 0.0132 0.68
_Method 2._--About 2 gm. of bismuth tribromphenate were placed in a
glass stoppered Erlenmeyer flask, 100 c.c. of alcohol were measured in
and shaken during one-half hour and allowed to stand over night. Fifty
c.c. of the supernatant liquid were then removed by means of a pipet,
a slight excess of tenth-normal sodium hydroxid added and the residual
alkali titrated with tenth-normal HCl.
Table 4 gives results obtained.
TABLE 4.--PER CENT. OF TRIBROMPHENOL BY METHOD 2
Gm. Tribromphenol
Calculated from Per Cent.
Gm. of Theoretical Free
Salt Taken Factor Tribromphenol
Research Council Spec. 2.0712 0.3905 18.85
Merck & Co. 1.9417 0.0760 3.92
Heyden Chemical Works 2.0440 0.0198 0.97
Table 5 gives a comparison of the results obtained by the two methods.
TABLE 5.--COMPARISON OF RESULTS BY METHODS 1 AND 2
Method 1 Method 2
Research Council Spec. 16.31 18.85
Merck & Co. 4.56 3.92
Heyden Chemical Works 0.68 0.97
The results obtained in Method 1 (the percolation method) apparently
are reliable and, as the method is the more simple, may be given
preference.
COMBINED TRIBROMPHENOL (TRIBROMPHENATE)
The amount of tribromphenol existing in the specimen in combination was
calculated by subtracting from the per cent. of total tribromphenol
determined, the per cent. of free tribromphenol found by Method 1.
The figures obtained are given in Table 6.
TABLE 6.--THE TRIBROMPHENATE CONTENT OF BISMUTH TRIBROMPHENATE
Per Cent. of
Combined
Tribromphenol
Research Council Specimen 43.13
Merck & Co. 53.19
Heyden Chemical Works 20.36
SUMMARY
From the foregoing the specimens examined contain the percentages
shown in Table 7 of bismuth (Bi), combined tribromphenate and free
tribromphenol.
TABLE 7.--PERCENTAGES OF BISMUTH AND OF COMBINED TRIBROMPHENATE AND
FREE TRIBROMPHENOL
Per Cent. Per Cent.
Per Cent. Combined Free
Bismuth Tribromphenate Tribromphenol
Research Council Specimen 44.8 43.13 16.31
Merck & Co. 46.6 53.19 4.56
Heyden Chemical Works 60.7 20.36 0.68
This examination shows:
1. The Bismuth Tribromphenolate submitted to the Council of
National Defense, does not correspond to the description of bismuth
tribromphenate in New and Nonofficial Remedies.
2. As now supplied, Xeroform-Heyden does not meet the requirements for
bismuth tribromphenate, nor does its composition correspond to that of
the product formerly supplied.
3. The description in New and Nonofficial Remedies of bismuth
tribromphenate should provide an upper, as well as a lower, limit
for the bismuth content; it should provide tests for the absence
of adulterants, and also set a limit of permissible uncombined
tribromphenol.
Report to Council of National Defense
The results of this examination with reference to the Research
Council specimen having been submitted to the Council on Pharmacy and
Chemistry, this body advised the Medical Section of the Council of
National Defense as follows:
1. The specimen of “Bismuth Tribromphenolate” sent to the Council
of National Defense complies with the New and Nonofficial Remedies
description for bismuth tribromphenate, except that it contains
considerable amounts (approximately 16 per cent.) of alcohol-soluble,
uncombined tribromphenol.
Revision of N. N. R. Standards
The results of the examination of the three specimens were sent
to the Heyden Chemical Works and to Merck and Co. (in each case
disclosing the identity of the particular firm’s product), asking
aid in the standardization of the product. After Merck and Co. had
submitted valuable advice for a revision of the somewhat loosely drawn
standards for bismuth tribromphenate in N. N. R., 1918, the inquiry
whether the following proposed revision of the description of bismuth
tribromphenate in New and Nonofficial Remedies was acceptable, was
submitted to both firms:
=BISMUTH TRIBROMPHENATE.--Bismuthi Tribromphenas.--Bismuth
Tribromphenol.--Xeroform.=--A basic bismuth tribromphenate of variable
composition.
An amorphous, yellow, nearly odorless and tasteless powder, neutral
to moistened litmus paper.
It is only slightly soluble in water, alcohol, chloroform, liquid
petrolatum and vegetable oils. Alkalies and strong acids decompose
it. It is stable at temperatures below 120 C.
When about 1 gm. of the salt is boiled with 10 c.c. of sodium
hydroxide test solution, the liquid filtered, and the filtrate
acidulated with sulphuric acid, the white curdy precipitate produced,
when washed and dried, melts at 90 to 95 C. (_tribromphenol_). The
contents of the filter dissolve completely in dilute hydrochloric
acid (insoluble _inert material_).
Boil 1 gm. of bismuth tribromphenate with 20 c.c. of a mixture of
equal parts of acetic acid and distilled water, cool the solution and
filter. Free the filtrate from bismuth by the addition of hydrogen
sulphide, boil the mixture and again filter. The latter filtrate
leaves not more than 0.005 gm. of residue on evaporation and gentle
ignition (_alkalies and alkali earths_).
Shake for one minute in a separatory funnel, 2 gm. of bismuth
tribromphenate, 20 c.c. of ether, and 20 c.c. of a mixture of
equal volumes of hydrochloric acid and distilled water. Draw off
the aqueous portion and concentrate to about 4 c.c.; pour it into
100 c.c. distilled water, filter, evaporate the filtrate on the water
bath to 30 c.c., again filter and divide this filtrate into portions
of 5 c.c. each. Mix one portion with an equal volume of dilute
sulphuric acid; it does not become cloudy (_lead_). Treat another
portion with a slight excess of ammonia water; the supernatant liquid
does not exhibit a bluish tint (_copper_). Another portion is not
immediately affected by barium nitrate test solution (_sulphate_).
Heat gently a mixture of about 0.2 gm. of bismuth tribromphenate
with 5 c.c. of potassium hydroxide test solution and about 0.2 gm.
of aluminum wire; the vapors evolved do not turn red litmus blue
(_nitrates_).
Shake 1 gm. of bismuth tribromphenate frequently during fifteen
minutes with 30 c.c. of alcohol (95 per cent.), filter and rinse
flask with two separate 10 c.c. portions of alcohol, allowing the
washings to run through filter. To the combined filtrate and washings
add 20 c.c. of tenth-normal sodium hydroxide and a few drops of
phenolphthalein solution and determine the excess of alkali with
tenth-normal hydrochloric acid. Not more than 1 c.c. of tenth-normal
sodium hydroxide should have been consumed by the alcoholic liquid
(_free tribromphenol_).
Add 2 c.c. of nitric acid to 2 gm. of bismuth tribromphenate in a
porcelain crucible, carefully evaporate to dryness on a sand bath
and incinerate. Dissolve the residue in 5 c.c. of concentrated
hydrochloric acid and add to the solution 10 c.c. of a saturated
solution of stannous chloride in concentrated hydrochloric acid. The
mixture should not darken on standing thirty minutes (_arsenic_).
Mix 0.5 gm. of the salt with 10 c.c. of a mixture of equal parts of
hydrochloric acid, U. S. P., and distilled water. No effervescence
should occur (_carbonate_).
To about 0.5 gm. of bismuth tribromphenate, accurately weighed, add
20 c.c. of hydrochloric acid and digest on water bath. Add 150 c.c.
of distilled water and filter. Rinse the beaker with 30 c.c. of
distilled water and allow the washings to run through the filter.
Saturate the combined filtrate and washings with hydrogen sulphide,
filter off the bismuth sulphide, wash and dissolve in hot dilute
nitric acid. Add a slight excess of ammonia water followed by 2 c.c.
of ammonium carbonate test solution. Allow to stand thirty minutes,
filter off the precipitated bismuth hydroxide and heat to constant
weight at dull red heat. The residue of bismuth oxide (Bi₂O₃) should
not be less than 45 per cent. nor more than 55 per cent. of the
original weight of bismuth tribromphenate taken, corresponding to not
less than 40 per cent. nor more than 49 per cent. of bismuth.
The Heyden Chemical Works accepted the proposed monograph. Regarding
the Laboratory’s findings, the firm stated that “the product had to be
made in this country after importations from Europe became impossible
and the first lots were not fully up to the standard.” Later the firm
stated that it could furnish a product which it considered equal to
that which was previously imported and offered to submit “samples of
the new material.”
Merck and Co. acknowledged the receipt of the monograph but made no
statement as to its acceptance or suggestions for its revision. As the
new monograph was accepted by the Heyden Chemical Works and as Merck
and Co. offered no objections, it was adopted for N. N. R., 1919, by
the Council on Pharmacy and Chemistry.
In November, 1918, Merck and Co. sent a specimen labeled “Bismuth
Tribromphenate-Merck,” “Merck and Co., New York, Distributors and
Guarantors” and wrote: “You will notice this sample conforms in nearly
all details to the tests submitted with our letter of June 4. We have
been able to produce better goods, but just at present unsatisfactory
starting material confronts us.”
Examination of the specimen demonstrated that it was soluble to a
considerable extent in alcohol (the N. N. R., 1918, description
provides that it should be only slightly soluble in alcohol) and,
according to the standards adopted for New and Nonofficial Remedies,
1919, contained 18 per cent. of uncombined tribromphenol (more than
five times the permitted amount).
In December, 1918, Merck and Co. submitted another specimen and said:
“We believe this is a better grade than we have been able to make in
the recent past. It seems to meet all the tests for N. N. R., 1919,
with two exceptions: these are (a) solubility in alcohol, and (b) the
test for uncombined tribromphenol.{”}
When the two recent samples of bismuth tribromphenate-Merck and two
samples of Xeroform-Heyden were examined according to the new monograph
the results given in Table 8 were obtained.
TABLE 8.--EXAMINATION OF TRIBROMPHENATE AND XEROFORM
1. BISMUTH.
Weight of Per Cent.
Weight Bi₂O₃ of
Brand and Date Received Taken, Obtained, Bismuth,
Gm. Gm. Gm.
Xeroform-Heyden (from mfr.) July, 1918 0.6754 0.3565 47.2
Xeroform-Heyden (open market) July, 1918 0.8259 0.6156 66.7
Bismuth tribromphenate-Merck Nov., 1918 0.4882 0.2512 46.1
Bismuth tribromphenate-Merck Dec., 1918 0.8869 0.4495 45.5
2. UNCOMBINED TRIBROMPHENOL.
No. C.c. Per Cent.
Weight of Tenth- of Free
Brand and Date Received Taken, Normal NaOH Tribrom-
Gm. Consumed, phenol
C.c.
Xeroform-Heyden (from mfr.) July, 1918 1 7.4 24.5
Xeroform-Heyden (open market) July, 1918 1 0.7 2.3
Bismuth Tribromphenate-Merck Nov., 1918 1 5.7 18.8
Bismuth Tribromphenate-Merck Dec., 1918 1 5 16.5
In view of the laboratory’s report the referee of the Council on
Pharmacy and Chemistry in charge of bismuth tribromphenate recommended
that the acceptance of Xeroform-Heyden and bismuth tribromphenate-Merck
be withdrawn, but that this should be without prejudice to their
reinstatement when satisfactory products are again offered for sale.
The Council adopted the recommendation of the referee and accordingly
Xeroform-Heyden and bismuth tribromphenate-Merck are omitted from New
and Nonofficial Remedies, 1919.
When the laboratory’s findings with regard to Xeroform-Heyden and the
action of the Council deleting the article from New and Nonofficial
Remedies was reported to the Heyden Chemical Works, the firm expressed
regret that efforts to produce a product equal to that formerly
obtained from Germany had so far not been successful and announced
that it had decided to withdraw Xeroform-Heyden from the market for
the present. When Merck and Co. was advised in regard to the report
of the laboratory and Council’s action, this firm questioned the
feasibility of producing a product meeting the Council’s standards and
suggested that the test for free tribromphenol be revised to permit
as much as 15 per cent. of this constituent. When Merck and Co. was
reminded that its product submitted in 1915 essentially complied with
the adopted standards (an old sample of Xeroform-Heyden was also found
to comply) and that the estimate of the therapeutic value of bismuth
tribromphenate is based on a product essentially devoid of free
tribromphenol, the firm replied:
“As stated in our letter of the 12th inst., we do not wish to market
the chemical unless it meets all legitimate requirements of the
physicians that use it. If, therefore, your standard proves to be good
and it is commercially possible to make supplies conforming to it, we
shall do so. We shall discontinue the article unless it is of suitable
quality.”--(_From Reports A. M. A. Chemical Laboratory, 1918, p. 93._)
THE STANDARDIZATION OF PROCAIN AND EXAMINATION OF THE MARKET SUPPLY
Procain, which chemically is the mono-hydrochlorid of
para-amino-benzoyldiethyl-amino-ethanol, is the nonproprietary name
selected by the Federal Trade Commission as the official designation
for the drug previously known under the proprietary name “novocaine.”
Before the war procain was obtainable in this country only through
the Farbwerke Hoechst Co., the American representative of the German
establishment, Farbwerke, vorm, Meister, Lucius and Bruening, under
the name “novocaine.” This monopoly on “novocaine” was exercised by
virtue of United States patent No. 812554, which was issued to Alfred
Einhorn, Munich, Germany, assignor to Farbwerke, vorm, Meister, Lucius
and Bruening, Hoechst a. M., in 1906. With the outbreak of hostilities,
Congress passed the Trading with the Enemy Act, and under this, the
Federal Trade Commission took charge of the novocain patent with a
view of securing the production of this product in the United States.
To ensure an adequate supply of the drug, the Federal Trade Commission
on recommendation of the Committee on Synthetic Drugs of the National
Research Council, in addition to issuing a license to the Farbwerke
Hoechst Company (which license was later transferred to the H. A. Metz
Laboratories) granted authority to the Abbott Laboratories and the
Rector Chemical Company to manufacture it under the U. S. patent after
specimens submitted by these firms had been found satisfactory in the
Association’s laboratory and at the Cornell Pharmacologic Laboratory.
When the first specimen of American made procain was sent to the
American Medical Association Chemical Laboratory it was necessary to
work out adequate standards. The standards were formulated on the basis
of the novocain monograph in the German Pharmacopeia, 1910, Ed. 5,
p. 363, Remedia “Hoechst,” p. 242, and New and Nonofficial Remedies,
1918, p. 32, and the work carried out in this laboratory.
The following description has been adopted for New and Nonofficial
Remedies, 1919, and all specimens of procain were subjected to these
tests:
Procain occurs in small colorless and odorless crystals, or a
crystalline powder which if placed on the tongue produces a transient
sense of numbness.
It melts at 153-155 C.[212]
[212] U. S. patent number 812,554--the novocain patent--declares
that the salt melts at 156 C. Evidently based on this, the German
Pharmacopoeia Remedia “Hoechst” and past editions of New and
Nonofficial Remedies give this melting point. Two specimens of German
made novocain obtained from our files, stated to be manufactured by
Farbwerke-Hoechst vorm. Meister, Lucius and Bruening, Hoechst a.M.
were found to melt, respectively, between 154 and 155 C. and between
153.5 and 154.5 C. when the melting point was determined according to
the directions of the U. S. Pharmacopoeia, 9th revision. The various
specimens examined at that time melted between 153 and 155 C. and it
was decided to permit this range.
One gm. of procain is soluble in 0.7 c.c. of water and in 20 c.c. of
alcohol U. S. P. (95 per cent.) at 20 C. From the aqueous solution,
which is neutral, alkali hydroxids and carbonates precipitate the
free base in the form of a colorless oil, which soon congeals to a
crystalline mass, but solutions of sodium bicarbonate are miscible with
solutions of procain without producing precipitations or turbidity.
Dissolve 1 gm. of procain in water. Separate portions of the solution
yield a white precipitate with potassium mercuric iodid solution,
a white precipitate with mercuric chlorid test solution, a brown
precipitate with iodin test solution and a yellow precipitate with
picric acid test solution. Acidify a portion with dilute nitric acid.
A white curdy precipitate is thrown down on the addition of silver
nitrate test solution.
Dissolve about 0.1 gm. of procain in 5 c.c. of water, add 2 drops of
dilute hydrochloric acid and 2 drops of sodium nitrite solution (10 per
cent.) and mix with a solution of 0.2 gm. of betanaphthol in 10 c.c. of
sodium hydroxid solution (10 per cent.). A scarlet red precipitate is
thrown down.
To a solution of about 0.1 gm. of procain in 5 c.c. of water add 3
drops of dilute sulphuric acid and mix with 5 drops of potassium
permanganate test solution. The violet color of the latter disappears
immediately (distinction from cocain).
Dissolve about 0.1 gm. procain in 1 c.c. sulphuric acid U. S. P. The
solution is colorless (organic impurities).
Dissolve 0.1 gm. of the salt in 10 c.c. of water and saturate with
hydrogen sulphid. No coloration or precipitation occurs (salts of the
heavy metals).
Incinerate about 0.5 gm. of procain accurately weighed. Not more than
0.1 per cent. of residue remains.
To obtain specimens representing the market supply, orders for the
three brands of procain were placed with pharmaceutical firms in New
York, Baltimore and San Francisco. The Baltimore and San Francisco
firms supplied specimens of procain-novocain brand and procain-Rector
brand but reported that the Abbott brand was not procurable. The
New York correspondent was able to supply procain-Rector only. As
the entire output of the Abbott Laboratories was stated to go to
the government, specimens of this product were obtained through the
surgeon-general of the army from the general purchasing office, Medical
Dept., U. S. Army. The following specimens were obtained and examined:
_1. Procain-Abbott, 6 specimens:_ The first specimen bore no serial
number but the five later specimens were designated respectively, No.
89999, No. 89998, No. 89997, No. 89996, and No. 810995, representing
batches from which shipments are to be made on contracts placed by the
general purchasing office, Medical Department, U. S. Army, with the
Abbott Laboratories of Chicago.
_2. Procain-novocain brand, 4 specimens:_ These were designated
respectively, A56, A57, A63, and A67. The first two specimens were
labeled “Manufactured by the Farbwerke-Hoechst Co. at the H. A.
Metz Laboratories.” The third specimen (not in original container)
was labeled “H. A. Metz Laboratories” and the fourth was marked
“Manufactured by the H. A. Metz Laboratories.”
_3. Procain-Rector, 3 specimens:_ Each bore the statement “Manufactured
by the Rector Chemical Company” but had no “lot number.”
From this examination it appears that all the specimens of procain
received complied satisfactorily with all tests of identity and purity
with the following exceptions: (1) One specimen of procain-Abbott had
a melting point slightly below the permitted range; however, the last
five specimens had the required melting point. (2) Five specimens of
procain-Abbott and the last three specimens of procain-Rector were not
entirely colorless, but had a yellow or light brown tinge.
The toxicity experiments, which were carried out by Dr. R. A. Hatcher
of the Cornell Pharmacologic Laboratory, were reported as being
satisfactory.
When the Council on Pharmacy and Chemistry referred the matter of
the discolored specimens of procain to the Rector Chemical Company
for explanation, the firm wrote that for a short time for some
unexplainable reason its procain had been slightly yellowish in color,
but that every batch had been carefully tested and found to answer all
chemical requirements. The firm stated that the product which it had
sent out for some time past had been white and yielded a colorless
solution.
To a like inquiry from the Council the Abbott Laboratories replied that
the five samples which were found discolored were products manufactured
by the Rector Chemical Company and represented goods which it had
purchased to assist in filling delayed orders, because the firm had
found itself unable to keep pace with the demand on account of delay in
securing needed apparatus. The firm submitted protocols to show that
the procain made by it, by Rector and by Metz were of equal toxicity.
In the accompanying table the results of the examination are given.
For comparison the findings for the specimens examined previously are
included.
====================================================================
Date Melting Ash
Brand Received Color Point, C. %
Procain (Abbott), from
Committee on Synthetic
Drugs 12/21/17 White 154-155 None
Procain (Abbott),
submitted to Council P.
and C 1/29/18 White 153.5-154.5 None
Procain (Abbott), Gen. Pur.
Off. U. S. Army 8/31/18 White 152.5-153.5 None
Procain (Abbott), Gen. Pur. Slight
Off. U. S. Army, No. 89999 9/30/18 brownish 153.5-154.5 None
tint
Procain (Abbott), Gen. Pur. Slight
Off. U. S. Army, No. 89998 9/30/18 brownish 153-154.5 0.005
tint
Procain (Abbott), Gen. Pur. Slight
Off. U. S. Army, No. 89997 10/ 8/18 brownish 153-154 None
tint
Procain (Abbott), Gen. Pur. Slight
Off. U. S. Army, No. 89996 11/ 4/18 brownish 153.5-154.5 None
tint
Procain (Abbott), Gen. Pur. Slight
Off. U. S. Army, No. 810995 11/ 4/18 brownish 153.5-154.5 None
tint
Procain (Farbwerke Hoechst
Co.), submitted to Council 10/24/17 White 153-154 None
Procain (Farbwerke Hoechst
Co.), submitted to Council 12/10/17 White 153-154.5 None
Procain (Farbwerke Hoechst
Co.), submitted to Council,
market spec. “A56” 8/ 9/18 White 153.5-154.5 None
Procain (Farbwerke Hoechst
Co.), submitted to Council,
market spec. “A57” 9/ 9/18 White 153.5-154.5 None
Procain (H. A. Metz Lab.),
market spec. “A63” 8/23/18 White 153-154 None
Procain (H. A. Metz Lab.),
market spec. “A67” 9/23/18 White 153-154 0.018
Procain (Rector), from Com.
on Synthetic Drugs 12/18/17 White 153-154.5 None
Procain (Rector), market Slight
spec. 8/20/18 brownish 153-155 None
tint
Procain (Rector), market Slight
spec. 8/23/18 brownish 153-155 None
tint
Procain (Rector), market Slight
spec. 8/23/18 brownish 153-154.5 None
tint
--------------------------------------------------------------------
So far as the evidence goes, there was nothing to indicate that the
yellowish or brownish colored specimens of procain were seriously
impure. On the contrary, the compliance with the chemical and
toxicologic tests indicated that the color was due to an insignificant
trace of some colored substance produced in the manufacturing process.
In view of this, the Council considered the use of the discolored
product to be justified in the present emergency, although it urged
that the future supply of procain should be free from color and also
comply to the tests of purity. It made this request in the interest of
the medical and dental professions, which use the drug, and also in a
desire that in the manufacture of synthetic drugs, the United States
should occupy a high place.--(_From The Journal A. M. A., Jan. 11,
1919, with additions._)
DETERIORATION OF SODIUM HYPOCHLORITE SOLUTIONS
(“Chlorinated Soda” Solutions)
The following note on two hypochlorite solutions is published as a
slight addition to the inconclusive available information concerning
the rate of deterioration of solutions containing sodium hypochlorite:
=Hyclorite.=--This is a solution of chlorinated soda, 100 gm. of
which is said to contain sodium hypochlorite 4.05 gm., sodium chlorid
3.20 gm., calcium hydroxid 0.25 gm., inert ingredients 0.92 gm. It is
declared to contain, when placed on the market, not less than 3.85 per
cent. of available chlorin, and to deteriorate at the rate of about
12 per cent. per year. In order that the available chlorin content
at the time of use may be judged, the date of bottling is stamped on
each package. The solution is prepared by decomposing chlorinated lime
suspended in water with sodium carbonate and adding to the solution
obtained a freshly prepared solution of electrolyzed sodium chlorid.
The composition and keeping qualities of hyclorite were reported on
by this laboratory (Ann. Rep. Chem. Lab., A. M. A. =9=:123, 1916).
Hyclorite is fully described in New and Nonofficial Remedies, 1918,
p. 153.
To further check the keeping qualities of hyclorite, a specimen
received from the manufacturer in June, 1918, and said to have been
bottled in April, 1918, was examined in September, 1918. It was found
to contain 3.6 per cent, “available chlorin” (equivalent to 3.79 gm.
sodium hypochlorite in 100 gm.). This indicated a loss of 6.2 per cent.
during five months (equivalent to 14.9 per cent. per year) on the
assumption that it contained the amount of “available chlorin” declared
on the label.
=Concentrated Solution Sodium Hypochlorite-Mulford.=--This is described
as a 5 per cent, aqueous solution of sodium hypochlorite containing
free chlorin equivalent to from 0.2 to 1 per cent. sodium hypochlorite.
It is prepared by treating a solution of sodium carbonate and sodium
bicarbonate with chlorinated lime. The solution is filtered and
standardized by determining the “available chlorin” and adjusting it to
contain the equivalent of 5 per cent. of sodium hypochlorite.
It is proposed for use in the irrigation treatment of infected wounds
after dilution with nine times its volume of water and the addition
of a determined amount (stated on the label of each bottle) of boric
acid to render it neutral to phenolphthalein. The manufacturer has
found that development of a red color (due to formation of permanganate
from the manganese contained in the chlorinated lime) is indicative
of deterioration, and therefore warns against any solution which has
become pink.
A specimen of concentrated solution of sodium hypochlorite-Mulford was
sent the Council on Pharmacy and Chemistry in June, 1917, with a view
of having the product admitted to New and Nonofficial Remedies. At
that time it was found to contain 4.18 per cent. “available chlorin”
(equivalent to 4.4 gm. sodium hypochlorite in 100 gm.). Another
specimen received at the same time and kept unopened in a dark place,
was examined in September, 1918, and was found to contain 2.88 per
cent. available chlorin (equivalent to 3 gm. sodium hypochlorite per
100 gm.). On the assumption that the second specimen contained, at
the time of its receipt, the amount of “available chlorin” found in
the first, this second specimen lost 31 per cent. of its “available
chlorin” during fifteen months.
At the time the specimens were received from the Mulford Company,
the firm reported experiments which were under way to determine the
keeping qualities of the solution. These experiments indicated marked
deterioration of the specimens, which had become red from permanganate
formation, and also that one specimen, which had not become red, had
lost 5 per cent. of its available chlorin in one month. The Mulford
Company explained that when sufficient data had been accumulated,
a decision would be made either as to placing a time limit on the
solution or making a claim as to the rate of deterioration. When the
extreme deterioration found by this laboratory was reported to the
Mulford Company, the firm replied that this was a much greater loss
than the average deterioration found in its chemical laboratory,
namely, an average of 10 or 12 per cent. per year. It advised that
because of the instability of concentrated solution of sodium
hypochlorite, its manufacture had been discontinued.--(_From Reports
A. M. A. Chemical Laboratory, 1918, p. 81._)
SYPHILODOL
The shortage of arsphenamin (salvarsan) has made the sale of
substitutes a profitable business. In many of these substitutes the
earmarks of dishonesty have been obvious, so that detection of their
falsity was relatively simple. In the case of “Syphilodol” marketed
by the French Medicinal Company, Inc., New York, the deception has
been practiced more skilfully. In the circular announcing their
preparations, we read:
“It seems fitting at this time, when the American physicians are
doing so much for France, that there should be a reciprocation in
some way.
“Attempting to enhance somewhat this mutual interchange, we are
presenting some of those scientific products, which have been so
successfully used in France, ----”
“The effect of SYPHILODOL is very similar to salvarsan and
neosalvarsan, but it has the advantage of being more lasting in
its results and more pleasing in the manner of its preparations,
in that it is put up in the form of tablets, and, also, in
hermetically closed glass syringes or ampules, so that it may be
administered either by the mouth, intravenously or intramuscularly,
at the discretion of the physician. Patients averse to the use of
the hypodermic needle may be treated expeditiously by the use of
the tablet form of the medicine.”
In addition to Syphilodol, the French Medicinal Co. also sells “Vichi
Fruti,” a combination of salts, “Urodol,” an “alkaline salt of the
famous European Springs which is noted for breaking up and dissolving
uric acid rapidly” and “Syloiodol,” “French Preventive,” which is
described as “a solution of iodol incorporated into bougie.”
“Syphilodol,” we are told, is “a synthetic chemical product of
_silver_, _arsenic_ and _antimony_, scientifically prepared after
the formula of the _late_ Dr. Alfred Fournier of Paris.” (Italics
ours--Ed.). It is also claimed that “Prof. Metchnikoff and other noted
French scientists have made exhaustive tests of syphilodol and found it
superior to the other products, in the treatment of syphilis.” In the
advertisements, Fournier and Metchnikoff are the only names given of
alleged endorsers; both of these men are dead and cannot protest. True,
Fournier did considerable work on a legitimate synthetic of antimony,
silver and arsenic having a general chemical constitution similar to
arsphenamin, but so far as we are aware, there has been no publication
by these men on “Syphilodol.” It would seem that the valuable work and
high reputation of Fournier and Metchnikoff are being capitalized by
the French Medicinal Company in their endeavor to foist a nostrum on
the medical profession of this country.
“Syphilodol” comes in two forms--ampules and tablets. An order for
two 0.4 ampules brought an elaborate case, much like those used to
hold the popular style safety razors. The ampule itself was a “classy”
affair evidently made by a glass expert; the hypodermic needle was
enclosed in a novel sealed glass device. The price of each ampule is
$3. No such fancy garnishments came with the tablets, although they are
listed at $4.50 for twenty-five--18 cents a tablet! In the “Syphilodol”
advertising it is emphasized that both the tablets and ampules are to
be administered. For example:
“Syphilodol is dispensed in the form of tablets and also
hermetically closed glass syringes or ampules so that it may be
used either by the mouth, intravenously or intramuscularly at
the discretion of the physician. An advantage of the tablets is
that they can and should be given during the interim between the
injections.”
LABORATORY REPORT ON SYPHILODOL
Several samples of “Syphilodol” were sent to the American Medical
Association Chemical Laboratory by readers of The Journal. An original
bottle of tablets was ordered direct from the French Medicinal Company.
The bottle contained 25 yellow tablets, having an average weight of
0.276 gm. (4-1/4 grains). After being powdered, “Syphilodol” was found
to be only partially soluble in water (the excipient is soluble) and
to be neutral in reaction. These findings contradict the claims on
the circular accompanying the bottle to the effect that “Syphilodol
is a yellow powder, soluble in water, and has an acid reaction.”
Qualitative tests indicated the presence of mercury, sucrose (cane
sugar), iodid, calcium, sulphate, fatty material, a trace of silver,
a trace of arsenic and a very minute trace of antimony; a red dye was
also present. Both qualitative and quantitative data showed that the
mercury was present in the form of mercurous iodid (yellow iodid of
mercury--hydrargyri iodidum flavum). Quantitative estimations yielded
the following:
Silver (Ag+) 0.001 per cent.
Mercury (Hg+) 11.1 per cent.
Iodid (I-) 7.8 per cent.
Sucrose (cane sugar) 72.0 per cent.
Ash (calcium sulphate) 2.5 per cent.
Ether-soluble material (fatty material--petrolatum) 3.5 per cent.
Thus each tablet of “Syphilodol” contains approximately, 3/4 grain
of mercurous iodid. An ampule of “Syphilodol,” labeled 0.4 gram,
contained approximately 1.5 c.c. of a liquid which after evaporation
on a water-bath left a residue weighing 0.8 mg., or 1/80 grain. A
second ampule held about 2 c.c. of liquid, which contained a trace of
arsenic (less than 0.00001 gm., or 1/6000 grain); a very small amount
of mercury was indicated but not definitely established. The liquid had
the physical characteristics of water.
Accompanying “Syphilodol” advertising sent to physicians is a circular
letter inviting the doctor to become a member in the “United States
Bacteriological and Research Institute.” The “institute” seems to be a
means of suggesting that the physician have bacteriologic, pathologic
and serologic examinations made on behalf of his patients. In view of
the fact that it is to the commercial interest of the French Medicinal
Company to have as many users of “Syphilodol” as possible, it would
be interesting to know what proportion of the Wassermann tests are
reported negative.
Shorn of its mystery, Syphilodol the “synthetic chemical product of
silver, arsenic and antimony” is essentially mercurous iodid--yellow
iodid of mercury.
Details of Analysis
SYPHILODOL TABLETS
In France there has been on the market for some time a synthetic
compound of silver, arsenic and antimony having the general structure
of arsphenamin. Structurally, the formula as given by Bonard, Danyss
and Tournier is (C₁₂H₁₂N₂As₂) 2AgBrSbO (H₂SO₄)₂--dioxy = diamino
arsenobensolstibicosilver sulphate. As the advertising matter for
“Syphilodol” referred to the synthetic compound of silver, antimony
and arsenic, and also to its use in syphilis by Fournier, the above
compound was first suspected. However, the general characteristics
of syphilodol tablets, such as partial solubility in water, but not
soluble in sodium hydroxid, sodium bicarbonate or acids, threw doubt on
the hypothesis. When a small amount of the powdered tablets was treated
with water, a yellow residue could be filtered off; the filtrate was
pink, opalescent, which on standing gave a clear pink solution, and
a small yellow precipitate. The residue, when allowed to remain in
sulphuric acid solution (20 per cent.) over night became red; on
boiling, the red precipitate with sulphuric acid, the precipitate
volatilized and could be condensed in a watch glass. Adding a pinch of
manganese dioxid to the hot sulphuric acid mixture caused an evolution
of iodin fumes. A small amount of powdered syphilodol tablets was
placed in the sunlight; they turned from yellow to black. All these
reactions are typical of mercurous iodid--yellow iodid of mercury.
MERCURY, SILVER, ARSENIC, ANTIMONY
I. _Mercury._--Two methods were used to determine the mercury: (_a_)
1.4535 gm. of powdered syphilodol was treated with 10 c.c. of a 50 per
cent. sodium sulphid solution. The solution was then transferred with
washings (about 20 c.c.) to a cathode cup, previously weighed with its
contained mercury. The mercury compound was electrolyzed by a current
of about 8 volts and 3 amperes, using a rotating anode. The solution
(and some sulphur suspension) was removed by siphon, pouring in water
until the amperage of the current was close to zero (U. S. P., IX,
p. 587). The increased weight in mercury was 0.1612 gm.
II. To serve as a check on the foregoing method, mercury was also
determined in the following method, which also allowed systematic tests
for silver, antimony and arsenic. (_b_) 1.1023 gm. of the sample was
placed in an Erlenmeyer flask, 50 c.c. of water, 50 c.c. of sodium
hydroxid solution (10 per cent.) and 20 c.c. of formaldehyd solution,
U. S. P., added. The solution was boiled for ten minutes and maintained
at temperature of steam bath for two hours. (This reduces the mercury
salt to mercury and any silver salt to silver; antimony would probably
be likewise reduced.) The precipitated mercury was transferred by
water, and concentrated nitric acid added. (The nitric acid solution
is boiled to oxidize all mercurous nitrate to mercuric nitrate.) A
small white precipitate was obtained at this point which seemed to be
insoluble in aqua regia (calcium sulphate). The filtrate from this
precipitate, which was washed well, was tested with one or two drops
of dilute hydrochloric acid and a faint precipitate formed; this was
filtered off through extra fine filter paper and washed repeatedly. The
paper and precipitate was heated with potassium cyanid solution over
night, filtered and the filtrate electrolyzed in a platinum dish. The
increase in weight of the dish was 0.00018 gm., or 0.001 per cent. Into
the platinum dish some nitric acid was poured, then diluted, and a drop
of hydrochloric acid added. A turbidity was produced which cleared on
the addition of excess of ammonium hydroxid solution (_silver_). The
filtrate from the nitric acid treatment was electrolyzed, this time in
a platinum dish, and the liquid carefully removed, washed carefully
with redistilled alcohol and ether. The mercury, which could be seen
easily by the naked eye, weighed 0.1200 gm., equivalent to 10.89 per
cent. of mercury.
III. _Arsenic and Antimony._--About 3 gm. of the powdered specimen was
digested with sulphuric acid in a Kjeldahl flask. One-half portion
(which was evaporated almost to dryness and treated with 5 c.c. of
concentrated hydrochloric acid) was submitted to treatment with
hydrogen sulphid, diluted, and saturated with hydrogen sulphid. The
precipitate was treated in the usual manner of the group separation
with warm ammonium sulphid solution. The filtrate from this treatment
was acidulated with hydrochloric acid, the precipitate removed, and
treated with concentrated hydrochloric acid. The substance insoluble
in hydrochloric acid was treated with more concentrated hydrochloric
acid and a crystal of potassium chlorate. The solution was tested after
the Gutzeit method of the Pharmacopeia IX, for _arsenic_. A very small
amount was indicated. The hydrogen sulphid test was not indicative. The
solution which might contain the _antimony_ was tested with hydrogen
sulphid. In one case only was a slight orange coloration produced. No
antimony was deposited on platinum foil in the presence of granulated
zinc. These tests were run in triplicate.
_Iodid._--Iodid was determined by the Carius method (_a_) 0.7412 gm.
yielded 0.1112 gm. silver iodid, equivalent to 8.09 per cent.; (_b_)
0.5319 gm. yielded 0.0751 gm., equivalent to 7.80 per cent. The iodid
and mercury were in proportions comparable to mercurous iodid.
_Ash._--(_a_) 0.9159 gm. when ignited to constant weight yielded
0.0232 gm., equivalent to 2.52 per cent. ash; (_b_) 1.3008 gm. treated
with water and the residue filtered on a Gooch filter and ignited.
The ash of the residue was 2.51 per cent. (the mercurous iodid
volatilized). The ash was calcium sulphate.
_Sucrose._--1.3008 gm. of the sample was treated with water and
filtered by suction through a Gooch crucible. The filtrate and washing
were carefully transferred to 500 c.c. volumetric flask, and allowed to
stand one week; 50 c.c. portions were used to determine sugar according
to the Daufresne-O’Sullivan method. The weights of cupric oxid averaged
210 mg., or 72 per cent.
_Ether Soluble Material._--1.6998 gm. of the powdered specimen was
extracted with ether and the ether extract evaporated to dryness. The
residue weighed 0.0600 gm., equivalent to 3.53 per cent.
SYPHILODOL AMPULES
_Water._--The liquid from one ampule was distilled over very carefully.
The freezing point of the liquid was +0.1 C., and it was neutral to
methyl orange and phenolphthalein.
_Arsenic._--The contents of one ampule was placed in a small florence
flask, 20 c.c. of concentrated sulphuric acid added and heated to
70 C.; 0.5 gm. of potassium permanganate was added in small amounts.
The procedure was then carried on as described by Engelhardt and
Winters in _J. Am. Pharm. Assn._, 1915, p. 1469. To the mixture
from 5 to 10 c.c. of hydrogen peroxid solution were added drop by
drop until the color had disappeared. The liquid was diluted with
20 c.c. of water, boiled fifteen minutes, diluted again and boiled
fifteen minutes, then cooled and made up to exactly 100 c.c. A blank
was also run alongside. Five c.c. of this solution was then tested
quantitatively for arsenic according to the U. S. P. IX method, using
all precautions. Comparisons of stains showed less than 0.00001 gm. of
arsenic (As).--(_From The Journal A. M. A., May 18, 1918._)
CERELENE
Cerelene, a paraffin preparation for the treatment of burns, was
submitted to the Council by the Holliday Laboratories, with the
statement that it was composed of 84 per cent. paraffin, 15 per cent.
myricyl palmitate, and 1 per cent. purified elemi gum to which is added
oil of eucalyptus 2 per cent. and betanaphthol 0.25 per cent. It was
explained:
“Myricyl Palmitate is a purified form of Beeswax, free from all
impurities, acids, etc., which is solely manufactured by this
Company....”
It was also stated that on “special order” Cerelene has been made
containing oil of eucalyptus and resorcin, oil of eucalyptus and picric
acid, and picric acid alone. The following report on the preparation
was presented to the Council by the referee to whom Cerelene had been
assigned:
Cerelene is another compound wax for the treatment of burns. According
to the work of Sollmann (J. A. M. A. =68=:1799, 1917) it is highly
improbable that compound mixtures have any advantage over simple
paraffin of low melting point. Cerelene must therefore be considered as
an unessential modification of paraffin, and as in conflict with Rule
10, unless definite evidence of superiority be submitted. Cerelene
mixtures containing medicinal ingredients also appear unscientific
since the evidence that the ingredients do not leave the wax has not
been successfully contradicted. Finally, the claims made for Cerelene
are rather extreme, and would need some revision before they could be
accepted.
The A. M. A. Chemical Laboratory reports:
The physical properties of Cerelene are as follows:
Melting point by U. S. P. method 50.0 C.
Ductility limit 30.5 C.
Plasticity limit 26.4 C.
Not strong at 38.0 C.
Adheres moderately well; detaches with “pulling.” On heating,
readily loses eucalyptol, and a small amount of resinous substance
forms in the bottom of the beaker. If Cerelene be heated to 145 C.
and cooled, the resulting product no longer has the properties of
the original Cerelene.
After two years’ delay on the part of the manufacturer, the Council
authorized publication declaring Cerelene inadmissible for New and
Nonofficial Remedies because its superiority over single paraffins
had not been demonstrated and the unwarranted claims had not been
abandoned.--(_Abstracted from The Journal A. M. A., Feb. 15, 1919._)
DR. DE SANCTIS’ RHEUMATIC AND GOUT PILLS
Dr. DeSanctis’ Rheumatic and Gout Pills are sold by Edward Cleaver, 13
Clerkenwell Road, London, England. The American agents are E. Fougera
and Co., Inc., New York. The package is a round pill box and contains
twelve pills and a circular, which directs that one pill be taken every
eight hours until relieved. In the package there is also a circular
advertising Dr. DeSanctis’ Gout and Rheumatic Paint, with directions
for its use. On the cover of a box, which contained six of the retail
packages, is the statement that these pills have been in general use
for nearly 100 years, and that their sale has been built up without
advertising.
DeSanctis’ pills are round, uncoated, and have a light brown color.
There was some variation in the color of different lots, one lot in
particular being gray rather than brown. A little arrowroot starch
was found in each box, this evidently having been used as a dusting
powder. The pills were very hard, rather brittle, but quite difficult
to powder. The pills were not readily disintegrated by water or diluted
acids, even when warmed, but when warmed with a dilute sodium hydroxid
solution they readily disintegrated.
Ten pills weighed 3.213 gm., an average of 0.3213 gm., or 5 grains. The
arrowroot starch used as a dusting powder was removed as completely as
possible by rolling the pills in a cloth. Several dozen pills were then
powdered and the powder thus obtained used for the analysis.
A microscopic examination of the powder showed powdered colchicum seed
in abundance and also traces of arrowroot starch, no doubt from that
used as the dusting powder.
Since colchicum seed was so abundant, the powder was assayed by the
U. S. Pharmacopeial method for colchicum seed (U. S. P. IX, p. 120),
slightly modified so that less of the powdered pills than directed
there could be used. In one assay 3.75 gm. gave 0.0204 gm. of colchicin
or 0.54 per cent. In a duplicate, 5 gm. gave 0.0234 gm. of colchicin or
0.47 per cent.; average 0.5 per cent.
The alkaloid obtained had the characteristic appearance and odor of
colchicin when separated from the seed under these conditions. The
solution in water and acid was yellow; the aqueous solution was
intensely bitter, and the yellow color intensified with acids. The dry
residue became intensely yellow with concentrated sulphuric acid; with
nitric acid it became violet turning to yellow, and with concentrated
sulphuric acid and potassium nitrate it gave a yellowish green color,
turning to violet and finally to a wine color. All these reactions are
typical of colchicin.
From 1 gm. of the powdered pills there was obtained 0.0425 gm. of ash,
or 4.25 per cent.
When the powdered pills were extracted with chloroform in a Soxhlet
apparatus, a very uniform quantity of extract was obtained. From 5 gm.
there was obtained, in one case, 0.581 gm.; in another, 0.5755 gm., and
in a third, 0.588 gm., the average being 0.5815 gm. or 11.63 per cent.
On still further extracting with alcohol, a small amount of extractive
was obtained, the amount depending on the length of time the extraction
was continued.
On extracting with hot water the residue left after exhaustion with
chloroform and with alcohol, a further extract was obtained. In one
case, it amounted to 0.4763 gm. or 9.53 per cent., and in another case
it amounted to 0.470 gm., or 9.40 per cent.; average 9.47 per cent.
In attempting to dry the pills or the above-mentioned chloroformic
extract at 100 C., a crystalline sublimate was obtained which had the
odor of benzoic acid. The crystals were acid, their neutral solution
gave a flesh-colored precipitate with ferric chlorid, and they melted
at 120-121 C. This crystalline substance appeared to be benzoic acid.
The quantity of benzoic acid in this extract was determined by heating
it to about 140 C. A current of air was drawn through the flask and
the sublimed benzoic acid collected in a cooled tube. The benzoic acid
was washed out of the tube with neutral alcohol, and the solution was
titrated with tenth normal potassium hydroxid. In one case, 11.25 c.c.
of tenth-normal alkali was used, indicating 0.1373 gm, of benzoic acid;
in another, 12.27 c.c., indicating 0.1498 gm. of benzoic acid; average
0.1436 gm., or 2.87 per cent. In a third case the temperature reached
250 C., and there was some decomposition of the fat in the flask and
some colored material distilled over. For this sublimate 15.54 c.c. of
tenth-normal alkali were required.
After evaporating the alcohol and acidulating the solutions obtained
in the previous experiments, the benzoic acid was extracted with
chloroform. In the first case, 0.1383 gm. was obtained; in the second,
0.1541 gm.; average 0.1462 gm., or 2.92 per cent. of benzoic acid.
When the original chloroformic extract was heated until all of the
benzoic acid had been driven off, the residue had the appearance of a
semisolid fat. It compared quite closely in color, odor, etc., with the
fatty material obtained by extracting colchicum seed with chloroform,
although the odor was more suggestive of oleic or stearic acid. It was
distinctly acid, which is also true of the fatty material obtained from
a sample of colchicum seed.
The extract obtained with hot water was light yellow; gummy, at first,
but dried to a glass-like brittle mass. It had a slight burned-sugar
odor and taste, and was neutral in reaction. It was strongly
dextrogyrate and at once reduced Fehling’s solution as well as alkaline
silver nitrate solution. On boiling with potassium hydroxid solution,
it turned deep red. It also gave the Molisch carbohydrate reaction,
and the ozazone test in seventeen minutes as described in Mulliken
(Identification of Pure Organic Compounds, Ed. 1, 1905, p. 26). These
are all characteristic reactions of lactose or milk sugar.
From this examination we conclude that DeSanctis’ pills contain
powdered colchicum seed, benzoic acid, and sugar of milk. There is also
present fatty material which resembles the fat of colchicum seed, but
may be, in part, added fatty acid. The percentage of colchicin found
(0.50) is about that of a good quality of colchicum seed, the U. S.
Pharmacopeial standard being not less than 0.45 per cent. Since the
pills contain material other than colchicum seed, this assay would
indicate a colchicum seed of high alkaloidal content, or the possible
reinforcement of the pills with colchicum extract or colchicin.
The amount of benzoic acid, 2.92 per cent., or about 1/7 grain per
pill, is insignificant from a therapeutic standpoint, since an average
dose is 0.5 gm., or 8 grains. Fatty acids, and the fatty matter from
colchicum seed are inert, at least in the quantities found here. The
only office which fatty acids might perform, would be to give the pills
an enteric quality, preventing their absorption until they reach the
intestine. The sugar of milk, about 10 per cent., or 1/2 grain per
pill, no doubt is simply an excipient.
DeSanctis’ pills are therefore essentially 5 grain doses of powdered
colchicum seed, of which the average dose is 0.2 gm., or 3 grains
(U. S. P. IX, p. 120).
The Journal in presenting the facts contained in the above report made
the following comments:
“Here then, we have sold for self-medication an extremely poisonous
drug, with no warning of the risk the public runs in using it. While
the directions call for “one pill every eight hours until relieved,”
it is notorious that the public takes the attitude toward “patent
medicines” that, if a little is good, more is better, and the average
user of remedies for self-treatment is likely, unless there is some
warning, to use his own discretion as to the amount taken.
“The individual dose is above that of the average recommended in the
United States Pharmacopeia. Colchicum or its alkaloids--or for that
matter, any drug as toxic as colchicum--have no place in preparations
of the home-remedy type. In the case of all “patent medicines,”
public interest demands that the full quantitative formula of the
therapeutically active ingredients should be given on the label, for
when the public prescribes for itself, it has a right to know what it
is taking. Unfortunately, public interest clashes with vested interests
and, as usual, vested interests get the better of it. In the case of
such dangerous preparations as DeSanctis’ pills, if their sale is to
be permitted at all, not only should the names and quantities of all
therapeutically active ingredients in the mixture be given, but the
law should require that the word Poison be plainly printed on the
label.”--(_Abstracted from The Journal A. M. A., July 19, 1919._)
IODEX AND LIQUID IODEX
The A. M. A. Chemical Laboratory examined Iodex in 1915.[213] The
claims made, at that time, by the exploiters, Menley & James, were
shown to be contrary to facts in that Iodex contained only traces of
free iodin while they claimed “5 per cent. Therapeutically Free Iodin.”
Even the _total_ quantity of iodin was shown to be only about one half
of the 5 per cent. claimed to be present as free iodin.
[213] Annual Reports of the Chem. Lab. of the A. M. A., 1915, p. 89.
An examination of the advertising matter sent out by Menley & James
in 1919 showed that substantially the same claims were being made as
in 1915. This at once suggested the inquiry: Since the claims are the
same as previously made, have the manufacturers altered the composition
to conform to the claims? The answer is found in the results of the
analysis of two samples purchased in the open market early in 1919.
This analysis shows conclusively that Iodex is essentially the same as
in 1915, that is, that it contains no free iodin and only about three
fifths of the total amount of iodin claimed.
It would seem that Iodex (Ung. Iodi., M. & J.) is in obvious conflict
with Section 7 of the Food and Drugs Act. While it is sold under a name
recognized by the U. S. Pharmacopeia, namely, Ung. Iodi., it does not
conform to the standards of the U. S. Pharmacopeia for that product.
Iodin ointment U. S. P. is made with 4 per cent. of free iodin, 4 per
cent. of potassium iodid, 12 per cent. of glycerin, and a benzoinated
lard base. It should then contain approximately 7 per cent. of total
iodin. It has been shown by Warren[214] that about 75 per cent. of the
iodin in the U. S. P. ointment remains in the free state even after
months of standing. Ung. Iodi., U. S. P., then, should contain about 3
per cent. of free iodin. Iodex contains no free iodin, or but traces,
and no potassium iodid. Furthermore, the Iodex label declares the
presence of 5 per cent. of “therapeutically free” iodin. As a matter of
fact, the amount of iodin is variable, the highest amount found being
3.5 per cent. and samples containing as low as 2.63 per cent. have been
examined.
[214] Warren, L. E.: Iodin Ointment, Am. J. Pharm., August, 1917,
p. 339.
It would seem further that Iodex is misbranded under the Sherley
amendment in that it is said that it “may be used externally with
advantage in all cases where the action of iodin is desired.” Since
it contains no iodin as such this cannot possibly be true. It is also
stated in a circular accompanying the trade package that “Thirty
minutes after inunction iodin can be found in the urine.” This
statement has also been shown to be untrue.--(_Annual Reports A. M. A.
Chem. Lab., 1915, p. 89._)
Details of Analysis
=Iodex.=--This is a rather soft ointment, almost black but with a
decided greenish cast in thin layers. It is soluble in chloroform
but is only partly saponified and dissolved by alcoholic potassium
hydroxid. Iodex has a distinct odor like oleic acid.
_Free Iodin._--When examined by the method previously used[215] only
minute traces of free iodin were found.
[215] Ibid., p. 90.
_Total Iodin._--The methods employed were as follows: 1. Iodex was
saponified by boiling for from two to three hours with alcoholic
potassium hydroxid. The alcohol was then evaporated and the iodin
determined by the method described in the U. S. Pharmacopeia for thymol
iodid.
2. The same as Method 1, except that after ignition of the saponified
mixture the halogen was determined by weighing as silver iodid.
3. The Carius method.
It should be noted that Methods 2 and 3 determine chlorin and bromin
should any be present with the iodin.
When 5 gm. of Sample 1 was assayed by Method 1, it required 73.56 c.c.
of tenth-normal sodium thiosulphate, equivalent to 3.11 per cent.
of iodin. In a duplicate, 2.7565 gm. of Iodex required 38 c.c. of
tenth-normal sodium thiosulphate, equivalent to 2.92 per cent. of
iodin; average of the two, 3.02 per cent. of iodin.
A weight of 2.5800 gm. of Sample 1, assayed by Method 2, gave
0.1582 gm. of silver halid, equivalent to 0.0855 gm. of iodin, or 3.31
per cent.
A weight of 0.588 gm. of Sample 2, assayed by the Carius method, gave
0.0388 gm. of silver halid, indicating 0.02096 gm. of iodin, or 3.52
per cent. In a duplicate, 0.5342 gm. gave 0.0338 gm. of silver halid,
indicating 0.01826 gm. of iodin, or 3.42 per cent.; average, 3.49 per
cent. of iodin.
=Liquid Iodex.=--This is sold by Menley & James, Ltd., the firm selling
Iodex Ointment. According to a circular in a trade package “the
valuable properties of Free Iodine are available in Liquid ‘Iodex’ in a
state of greatly enhanced activity; but the irritating, corrosive and
hardening drawbacks of ordinary solutions of the drug are absent.” The
label on a bottle reads as follows: “Liquid ‘Iodex’ (Liq. Iodi. M.
& J.). A nonirritant preparation of iodine (2-1/2%) ... This product
contains Free Iodine....”
The sample of Liquid Iodex purchased on the open market was found to be
a reddish liquid with an odor like oleic acid. It dissolved completely
in chloroform.
_Free Iodin._--A weight of 6.2936 gm. was dissolved in chloroform and
the solution shaken with 25 c.c. of a solution of potassium iodid.
The iodin which passed into the potassium iodid solution was titrated
with tenth-normal sodium thiosulphate, 0.81 c.c. being required. This
indicates 0.01022 gm. of iodin, or 0.16 per cent.
_Total Iodin._--Total iodin was determined by Method 1 as given above
under Iodex. A weight of 4.466 gm. required 32.93 c.c. of tenth-normal
sodium thiosulphate, equivalent to 0.06964 gm. of iodin, or 1.55
per cent. In a duplicate, 5 gm. of material required 33.3 c.c. of
tenth-normal sodium thiosulphate, equivalent to 0.7043 gm. of iodin, or
1.41 per cent.; average, 1.48 per cent. of iodin.
Liquid Iodex, then, contains but little (0.16 per cent.) free iodin and
only about three fifths of the total iodin claimed.
I. G. O.
I. G. O. is an iodin ointment. It is said to be made by Dr. H. S.
Lambdin, Peru, Kansas. In a circular distributed by the manufacturer,
it is stated that “I. G. O. is a saturated solution of Iodine Gas in
petrolatum at 130 degrees with oil of eucalyptus. The heat of the body
liberates the iodine and it is absorbed as free iodine.”
A sample of I. G. O., received from a physician, was examined. It was
found to be a black ointment, green in thin layers, with a slight odor
like crude petroleum. By the methods used for the examination of Iodex,
I. G. O. was found to contain 0.59 per cent. of free iodin.--(_From
Reports A. M. A. Chemical Laboratory, 1919, p. 104._)
IODIN IN LIQUID PETROLATUM
A. H. Clark, Ph.G., Sc.B.
Of all the things used in medicine nothing seems to have attracted
the attention of all classes of users as has iodin. Perhaps more
romantic schemes for the cure of all the ills which afflict mankind
have centered in iodin therapy than in any other one drug. Iodin is
being used in every conceivable way from crystals to colloid; in vapor;
combined as iodid, iodate and the like; organic, inorganic, simple and
complex; internal, external and by injection, and yet there seems to be
no end to the ingenious schemes for its exploitation.
One of these schemes, and one so simple that it seems at first sight
to be hardly worth serious consideration, is that of a solution of
iodin in liquid petrolatum. Solutions of this kind have frequently been
offered to physicians and the laity. The thing of particular interest
is the claim made as to the percentage of free iodin. Five per cent.
is frequently claimed. Examination of some of these products in the
chemical laboratory of the A. M. A.[216] revealed the fact that they
did not contain the claimed amount of free iodin. These questions at
once arose: Was the low free iodin content due to intentional fraud,
the result of carelessness, or of ignorance? Was it impossible to
prepare a solution containing 5 per cent., or did the iodin slowly
combine with the oil and disappear?
[216] Reports A. M. A. Chemical Laboratory, 1915, p. 106; Ibid., 1917,
p. 87.
Several years ago the A. M. A. Chemical Laboratory[217] conducted some
experiments on the solubility of iodin in liquid petrolatum, which
indicated that a saturated solution would contain about 1.4 per cent.
These experiments did not show conclusively that no iodin was absorbed
by the petrolatum during the process of solution. For this reason,
further experiments were conducted with the view of determining both
the solubility in and the extent to which iodin is absorbed (disappears
as free iodin), if at all, by liquid petrolatums of various kinds.
Theoretically such hydrocarbons should not absorb iodin. The results of
these experiments are here given.
[217] Ibid., 1917, p. 87.
A sample of iodin was prepared by sublimation from a mixture with
potassium iodid. This sample when dried over sulphuric acid assayed
99.98 per cent. of iodin. Portions of this sample were used in all
of the subsequent experiments. To prepare solutions of definite
concentrations, in all cases expressed as percentage by weight, an
accurately weighed quantity of iodin was placed in a glass-stoppered
bottle and an accurately weighed quantity of liquid petrolatum added.
The mixture was subjected to treatment as indicated in the various
experiments and from the weights of iodin and petrolatum used the
percentage of iodin was calculated.
The method of assay employed was as follows: A weighed quantity of
the iodin solution was transferred to a bottle or flask by means of
several small amounts of chloroform, about 50 c.c. in all. To this
was added about 25 c.c. of potassium iodid solution. The mixture was
then titrated with tenth-normal sodium thiosulphate until on thorough
shaking no iodin passed into the aqueous layer.
To 2.1248 gm. of iodin was added 199.3 gm. of liquid petrolatum.
The mixture was shaken frequently each day and after forty days
there seemed to be still a few particles of iodin undissolved. The
supernatant solution was assayed, however, and found to contain 1.038
per cent. of iodin. The iodin added was 1.055 per cent. Six months
later 1.025 per cent. of iodin was found.
To 5.1832 gm. of iodin was added 199.5 gm. of liquid petrolatum. The
mixture was heated to 100 C. for four hours with frequent shaking.
The iodin was in perfect solution. The per cent. of iodin would then
be 4.95. Upon cooling, iodin in abundance crystallized out. After
standing a few hours, with frequent shaking, the iodin in solution was
determined. This was found to be 1.425 per cent.
These two experiments indicate: First, that the previous findings of
the A. M. A. Chemical Laboratory are correct in that only about 1.4
per cent. of free iodin is retained in solution in liquid petrolatum
at room temperature. Second, that the quantity of iodin absorbed by
liquid petrolatum at room temperature, in seven months at least, is
practically none. Third, that iodin dissolves rather slowly in liquid
petrolatum at room temperature.
In the experiments, the results of which are tabulated below, the iodin
and liquid petrolatum were heated at 100 C. for about four hours,
shaking frequently to hasten solution. After cooling, the specimens
were assayed and were again assayed at intervals as indicated in the
table.
Date of Per Per
Kind of Manufac- Weight Per Per Cent. Cent.
Liquid ture and ┌─────┴─────┐ Cent. Cent. Iodin Iodin†
Petrolatum First Iodin Petrolatum Iodin Iodin Nov. 17, Nov. 19,
Used Assay Used Found 1918 1919
Stanolind 10/17/18 2.089 188.4 1.096 1.085 1.068 1.067
Squibb 10/14/18 1.9569 186.78 1.0306 1.0232 1.013 1.009
Unknown, bulk* 10/28/18 1.9497 158.2 1.225 1.133 1.075 1.095
Parke, Davis 10/24/18 2.0869 167.43 1.241 1.2488 1.191 1.180
& Co
* Considerable dark sediment formed in this sample during the heating
process.
† It should be pointed out here that while every sample showed some
absorption, the amount, with the exception of the unknown bulk,
is so small that it might even be accounted for on the basis of
“experimental error.” Every ordinary precaution was taken to insure
accuracy, but since about 15 gm. of the solution was used for each
determination, it is seen that an error of 0.3 c.c. in the titration
would indicate a greater absorption of iodin than that noted.
Conclusions: These experiments show: A solution of iodin in liquid
petrolatum is saturated when it contains about 1.4 per cent. of iodin.
The amount of iodin absorbed (disappearing as free iodin) by liquid
petrolatum, when in contact at room temperature for as long as seven
months, or in contact at 100 C. for four hours, or both, is relatively
insignificant. Also all the absorption seems to take place during the
heating and in the first month of contact.--(_From Reports A. M. A.
Chemical Laboratory, 1919, p. 21._)
AMERICAN-MADE SYNTHETIC DRUGS--II
Examination of Procain (Novocain), Barbital (Veronal), Phenetidyl-
Acetphenetidin (Holocain), Cinchophen or Phenylcinchoninic
Acid (Atophan), Manufactured Under Federal
Trade Commission Licenses[G]
Paul Nicholas Leech, Ph.D.; William Rabak, Ph.G., Sc.B.,
and A. H. Clark, Ph.G., Sc.B.
[G] From the Chemical Laboratory of the American Medical Association.
[G] The first article of this series dealt with the purity of
acetylsalicylic acid. Leech, P. N.: Examination of American-Made
Acetylsalicylic Acid, J. Indust. & Engin. Chem., April, 1918, p. 288.
“What’s in a Name?” ibid., p. 255. Acetylsalicylic Acid, or “What’s in
a Name?” Editorial, J. A. M. A. 70: 1097 (April 13) 1918.
Before European hostilities, the United States was so dependent on
Germany for synthetic drugs that the dependence was considered a
necessity; this was strikingly manifested by the precipitous rise in
prices immediately after the embargo was declared against Germany.
Since then the shortage of German-made synthetics has caused two
important results: 1. The physician can do without most of the German
drugs, because the prewar demand had been stimulated artificially.
2. Those few synthetics, which were in great need, are being rapidly
replaced by the American-made drugs.[218] In connection with the second
result, the Chemical Laboratory of the American Medical Association has
endeavored to contribute its services.
[218] Stieglitz, Julius: Synthetic Drugs II, J. A. M. A. 70: 688
(March 9) 1918. Leech, P. N.: The Vindication of the American Chemist;
Synthetic Drugs, Chicago Chem. Bull. January, 1918, p. 230.
In September, 1917, it was announced[219] that the A. M. A. Chemical
Laboratory would make studies of American-made synthetics. Just prior
to this announcement, the National Research Council established a
committee on synthetic drugs[220] “to facilitate the manufacture of
synthetic drugs in this country and thus to relieve shortage and reduce
the exorbitant prices which have resulted from the war.”[221] Also
during this time Congress was considering the “trading with enemy” act,
first known as the Adamson bill--the purpose of which was to confer
authority on the President to license American firms to use U. S.
patents owned by German subjects. The act became law, September 28; the
Federal Trade Commission was designated by the President to carry out
the provisions of the law as it referred to enemy-owned patents. As a
result of a conference, Oct. 30, 1917,[222] with various agencies, the
Federal Trade Commission decided to consider licenses for manufacturers
of synthetic drugs, _after_ recommendations had been made by the
Committee on Synthetic Drugs of the National Research Council; this
committee in turn invoked the aid of the A. M. A. Chemical Laboratory
in testing the manufacturer’s products. The essence of the laboratory’s
work up to July 1, 1919, is reported in this paper.
[219] The Quality of American-Made Synthetics, J. A. M. A. 69: 1018
(Sept. 22) 1917.
[220] This committee is composed of Julius Stieglitz, chairman,
professor of chemistry, University of Chicago; W. A. Puckner, secretary
of the Council on Pharmacy and Chemistry, American Medical Association,
and Moses Gomberg, professor of chemistry, University of Michigan.
[221] Stieglitz, Julius: Shortage of Synthetic Remedies, J. A. M. A.
69: 400 (Aug. 4) 1917.
[222] Foreign Patents to Be Open to American Manufacturers, J. A. M. A.
69: 1550 (Nov. 3) 1917.
THE NAMING OF LICENSED DRUGS
“Partly in order to help insure to licensees a market for their
products after the war, in larger part inspired by the idea of
encouraging the establishment of a permanent American industry in these
important articles, the [Federal Trade] Commission wisely decided that
American houses should be put on the same footing as competing foreign
houses for after-the-war competition, by imposing on all licensees
the obligation to use _new official names_ for the articles, names
which after the war will be open to all competitors, domestic and
foreign.”[223]
[223] For an interesting discussion, see Stieglitz, Julius: Synthetic
Drugs, J. A. M. A. 70: 536 (Feb. 23); 688 (March 9); 923 (March 30)
1918. Bracken, L. L.: Federal Trade Commission Requests Use of Official
Names, ibid. 70: 558 (Feb. 23) 1918.
The new American names are:
Arsphenamin[224] (contracted from the scientific name arsenphenolamin)
for salvarsan, arsenobenzol, diarsanol, arsaminol.
[224] The testing and standardizing of arsphenamin is being done by the
Hygienic Laboratory, U. S. Public Health Service. For chemical tests
see reprint 472, Public Health Reports. For a review of the patent
literature see article by H. F. Lewis, J. Indust. Engin. Chem., Feb. 1,
1919, p. 141.
Barbital (contracted from the scientific name diethyl-barbituric acid)
for veronal.
Barbital-sodium (the sodium salt of barbital) for “veronal-sodium” and
“medinal.”
Cinchophen for atophan or phenylcinchoninic acid (the U. S. P. IX name).
Procain for novocain hydrochlorid (from “pro” and “(co)caine”).
Procain nitrate for novocain nitrate.
EXAMINATION OF SYNTHETIC DRUGS
In testing chemically the products which had been submitted to the
Federal Trade Commission, the aims were that the product should conform
to a high degree of purity; at the same time the candidate for license
should not be inflicted with undue hardships in making the product,
such as an unnecessarily high degree of purity. It was insisted that
the purity of the drugs should be equal to, if not greater than, that
of the respective former German-made products, in order to uphold the
name and reputation of the American manufacturers in the after-the-war
competition. Consequently, in the chemical work the American product
was always examined parallel with the German-made product, authentic
samples of the latter of which the laboratory had in its possession.
Whenever possible, the tests described in books of standards were
carried out.
BARBITAL (VERONAL)
Barbital was introduced into medicine under the proprietary name
“veronal,” and was manufactured in Germany by Friedr. Bayer &
Co., Leverkusen, and E. Merck & Co., Darmstadt, Germany. Barbital
is described in New and Nonofficial Remedies, 1919,[225] as
diethylbarbituric acid (diethylmalonyl urea) having the formula:
NH—CO C₂H₅
/ \ /
OC C
\ / \
NH—CO C₂H₅
[225] New and Nonofficial Remedies, 1919, published by The Council on
Pharmacy and Chemistry of the American Medical Association, p. 82.
It is official in the British Pharmacopeia under the name
“barbitone,” and in the German Pharmacopeia as “acidum
diethylbarbituricum.” Barbital “may be prepared by the interaction
of esters of diethylmalonic acid with urea in the presence of
metallic alcoholates.... It is also obtained by condensation of
diethylcyanacetic ester with urea by means of sodium alcoholate.”
Barbital is used in medicine chiefly as a hypnotic.
The different brands of barbital which were submitted to the laboratory
were subjected to the tests given in the books referred to above.[226]
The products were:
[226] The pharmaceutic monograph on barbital has been omitted. It was
published in the 1918 edition of the Annual Reports of the Chemical
Laboratory of the American Medical Association.
1. Barbital (Abbott) Sample A, to Federal Trade Commission.
2. Barbital (Abbott) Sample B, to Federal Trade Commission.
3. Barbital (Abbott) Sample C, to Red Cross.
4. Barbital (Antoine Chiris), to Federal Trade Commission.
5. Barbital (V. Halter), to Federal Trade Commission.
6. Barbital (Rector Chemical Company) to Federal Trade Commission.
7. Diethylbarbituric acid (Merck), to Council.
8. “Veronal,” manufactured by Farb. vorm Fried. Bayer & Co., Germany.
All responded satisfactorily to the tests. In Table 1 are given the
respective melting points and percentages of ash found. (The melting
point of a mixture of the sample with the original “veronal” was always
taken.)
TABLE 1.--MELTING POINT
Ash Ash
1 188.5-189.0 0.01 5 188.0-188.5 0.01
2 188.5-189.0 0.01 6 188.0-188.5 0.01
3 188.0-188.5 0.01 7 188.0-188.5 0.01
4 188.0-188.5 0.04 8 188.0-188.5 0.02
Barbital does not seem to form an insoluble salt with chlorplatinic
acid; nor an ether-insoluble hydrochlorid or oxalate; nor an insoluble
barium salt. It does not respond to many urea tests, and is not
affected by urease as would be expected in light of the extensive
investigations made on this enzyme by Van Slyke and Cullen.
As barbital is also sold in the form of tablets or mixtures, a reliable
method for its quantitative determination in the presence of other
substances is needed. Some experiments in this direction were made, but
the press of other work did not permit their continuation. When time
permits, this work will be resumed.
At the time of writing this article, licenses for manufacture had been
granted by the Federal Trade Commission to the Abbott Laboratories, to
Antoine Chiris Company, and to the Rector Chemical Company.
BARBITAL SODIUM (MEDINAL OR VERONAL-SODIUM)
Barbital sodium, formerly sold under the proprietary names
“veronal-sodium” and “medinal,” is, as the former name suggests, the
sodium salt of diethylbarbituric acid. Its therapeutic advantages
are stated to be that more rapid results are obtained because of
its increased solubility over barbital alone.[227] Barbital sodium
should yield, according to theory, 11.19 per cent. of sodium and 89.31
per cent. of diethylbarbituric acid. A number of years ago, when
“veronal-sodium” and “medinal” were being introduced, Puckner and
Hilpert[228] found that these products yielded results corresponding
closely to the theoretical amounts of sodium and diethylbarbituric
acid. A recent examination of veronal-sodium, Merck, made for the
Council on Pharmacy and Chemistry, showed it to be of the same
composition as that previously reported.
[227] New and Nonofficial Remedies, 1918, p. 96.
[228] Puckner, W. A., and Hilpert, W. S.: Veronal-Sodium and Medinal,
J. A. M. A. =52=:311 (Jan. 23) 1909; Rep. A. M. A. Chemical Lab.,
=2=:13.
Only one firm’s product has been submitted to the laboratory through
the Committee on Synthetic Drugs, but because of the unsatisfactory
results, it was not recommended for license, nor, as far as we are
aware, has the firm investigated its anomalies.[229] The amount of
moisture in this specimen was 0.04 per cent. It yielded 10.94 and 10.97
per cent, of sodium. Puckner and Hilpert found 11.02 per cent. of
sodium in “medinal,” and 11.01 per cent. of sodium in “veronal-sodium.”
The theoretical amount, according to the formula given for medinal by
the proprietors (C₂H₅)₂ CCONNaCONHCO is 11.19 per cent. When an aqueous
└───────┘
solution of barbital sodium was acidified, and the diethylbarbituric
acid extracted with ether, it was found that theamount of freed acid
extracted varied directly with the length of time after acidification.
[229] Since this was written, the Council on Pharmacy and Chemistry has
also accepted “Barbital-Sodium Abbott.”
It is possible that in preparing the sodium salt of diethylbarbituric
acid, the ring opens up, forming a compound not so easily affected by
dilute mineral acids.
TABLE 2.--EXTRACTION OF A SAMPLE OF BARBITAL-SODIUM
Diethylbarbituric Acid
Length of Time per Cent.
a. Immediately 75.5
a^1. 3/4 hour 82.0
b. Immediately 82.0
c. 1-1/2 hours 80.5
d. 4 hours 82.82
e. 4 hours 83.56
f. 4 hours 83.41
g. 45-1/2 hours 84.89
h. 45-1/2 hours 84.73
Theory ........ 89.31
Veronal-Sodium (Puckner and Hilpert) 89.01 (average)
Medinal (Puckner and Hilpert) 88.95 (average)
PHENETIDYL-ACETPHENETIDIN HYDROCHLORID[230] (HOLOCAIN HYDROCHLORID)
Phenetidyl-acetphenetidin hydrochlorid was introduced in the
United States under the name of “holocain hydrochloride” by
Farbwerke, vorm Meister Lucius and Bruening, Hoechst a. M. Germany;
the product apparently had not been patented in this country,
although it was protected in Germany under patents No. 78868 and
80568. New and Nonofficial Remedies, 1918, describes “holocain
hydrochlorid” as ethenyl-paradiethoxy-diphenyl-amidin hydrochlorid
CH₃:(NC₆H₄OC₂H₅)(NHC₆H₄OC₂H₅)HCl. It is used as a local anesthetic for
the eye.
[230] No short, scientific name has been given for this substance
although several are under consideration.
The standards, such as had been described, were meager and
unsatisfactory. Hence when the first specimen of American-made
phenetidyl-acetphenetidin was sent to the A. M. A. Chemical Laboratory
through the agency of the Federal Trade Commission and the Committee
on Synthetic Drugs, it was necessary for the laboratory to work out
adequate standards.[231] As a result of the chemical work, a rather
comprehensive monograph was drawn up, which was published in the 1918
Laboratory Reports. A summary of the products examined, with some
of the chemical data, is given in Table 3. It will be seen that one
specimen had a deficiency of about 2 per cent. of free base.
[231] Certain chemical tests are described by E. H. Rankin, Indian
J. M. Res. =4=:237, 1916; also Chem. Abst. =10=:524. Other references
are Schmidt: Pharmazeutische Chemie =2=:990, Beilstein II, (403).
Arends, G.: Neue Arzneimittel und pharmazeutische Spezialitäten, Ed. 4,
1913, p. 271.
TABLE 3.--DATA ON PHENETIDYL-ACETPHENETIDIN HYDROCHLORID [table split
by transcriber to fit small screen]
======================================================================
Melting Phosphorus
Manufacturer Appearance Moisture Point Compounds Phenetidin*
John T. White 5.13 191.5 to 192 Absent Negative
Milliken Co. crystalline
powder
Synthetic White 2.90 192 to 192.5 Absent Negative
Products Co. crystalline
powder
H. A. Metz White 4.99 192 to 192.5 Absent Negative
Laboratories, crystalline
Inc. powder
Farbwerke- Slightly 5.09 190 to 191 Absent Negative
Hoechst Co. pink
(German crystal
specimen)
----------------------------------------------------------------------
======================================================================
Per Per Per Cent.
Cent. Cent. Melting Platinum in
Indol Base by Base by Point Platinum
Manufacturer Reaction Ash Weight Titration of Base Salt +
John T.
Milliken Co. Positive 0.00 89.16 89.16 116 to 117 19.02
Synthetic
Products Co. Positive 0.13 87.49 87.26 116 to 117 19.3
H. A. Metz
Laboratories, Positive 0.00 89.14 88.55 117 19.34
Inc.
Farbwerke-
Hoechst Co. Positive 0.16 89.65 89.64 116 to 117 19.00
(German
specimen)
----------------------------------------------------------------------
* The phenetidin test is not very sensitive.
The melting point of the free base is given by a number of writers at
121 C. Although Kennert[232] stated it to be 117 C. and not 121 C., his
findings seemingly went unheeded. It will be noted that our work shows
the melting point to be in accord with that announced by Kennert.
[232] Kennert: Chem. Zentralbl. =2=:556, 1897.
The Federal Trade Commission has not issued any licenses for the
manufacture of “holocain hydrochlorid.” The John T. Milliken Company
has withdrawn its application. The H. A. Metz Laboratories (Successor
to Farbwerke Hoechst Company, New York) are making the product in this
country.
CINCHOPHEN (PHENYLCINCHONINIC ACID, U. S. P.; ATOPHAN)
Cinchophen (phenylcinchoninic acid) was introduced in the United States
as a medicine under the proprietary name “atophan,” by Schering and
Glatz, New York City, who before the war were the American agents for
the German manufacturers “Chemische Fabric auf Actien von E. Schering,
Berlin.” Phenylcinchoninic acid (2 phenyl-quinolin-4 carboxylic acid)
was first described by Doebner and Gieseke[233] in 1887, who prepared
it by warming together pyro-racemic acid, benzaldehyd and anilin in
alcoholic solution; it has the structural formula:
COOH
╽
╱╲ ╱╲ __
╽ ╽ ╽__╱ ╲
╲╱ ╲╱ ╲ __╱
N
[233] Doebner and Gieseke: Ann. d. Chem. (Liebigs) =240=:291, 1887.
The chief use of phenylcinchoninic acid is as an antiuric acid agent,
especially indicated in gout.
In 1913, the German house of Schering was made the assignee of
patent 1045759 granted by the United States government[234] for the
manufacture of phenylcinchoninic acid: at about the same time the
product was admitted to the U. S. Pharmacopeia IX, under very loosely
constructed standards.
[234] The validity of this patent is to be doubted.
Some time after the beginning of the European war the proprietary
“atophan” became scarce in America. In 1917, however, Schering and
Glatz, New York, placed American-made atophan on the market and
submitted it to the Council on Pharmacy and Chemistry. Later, other
firms began to manufacture the product and also submitted specimens.
During the time it was investigating these products, the Federal
Trade Commission decided that a license was needed to manufacture
phenylcinchoninic acid under the patent just referred to, so that
altogether the laboratory had a number of specimens to examine.
In making the examinations for the Council, the laboratory was
practically confined, by virtue of the Food and Drugs Law, to limit
its requirements of purity to those of the Pharmacopeia. Practically,
the only tests were melting point, ash and solubility. According
to the U. S. Pharmacopeia the melting point is “about 210.” In New
and Nonofficial Remedies, 1918, it was explained that atophan
“complies with the standards for phenylcinchoninic acid, U. S. P.,
but melts between 208 and 212 C.” The U. S. Pharmacopeia requires
that no weighable ash remains on incinerating about 0.5 gm. of
phenylcinchoninic acid. Considerable variations, especially in melting
points, were found, as can be seen from Table 4.
TABLE 4.--MELTING POINTS AND ASH
Product Manufacturer Melting Ash,
No. Point, C. %
1 Abbott Laboratories, Chicago 208.5-210.5 0.05
2 Abbott Laboratories, Chicago 212-213 0.05
1 Calco Chem. Co., Bound Brook 209-210.5 0.07
1 Morgenstern, New York 204.5-207.5 2.8
2 Morgenstern, New York 208.5-211.5 None
1 Schering and Glatz, New York 206-208 None
2 Schering and Glatz, New York 209-211 None
3 Schering and Glatz, New York 208.5-210 0.17
4a Schering and Glatz, New York (1) 208.5-210 0.2
4b Schering and Glatz, New York (2) 208.5-209.5 0.3
4c Schering and Glatz, New York (3) 208.5-210 0.025
1 Wm. H. Sweet and Co., Columbus 204-208 None
2 Wm. H. Sweet and Co., Columbus 209.5-211.5 0.04
1 German specimen from Schering and Glatz 210-212 None
By referring to this table on melting points and ash content it will be
noted that the production of a better grade of products resulted after
the respective firms had submitted samples to the A. M. A. Chemical
Laboratory for criticism, and from a chemical standpoint, the last
products examined were found to be as satisfactory as the German-made
“atophan.”
_Solubility of Cinchophen (Phenylcinchoninic Acid)._--As methods
of determining impurities, or estimating the degree of purity of
phenylcinchoninic acid were not described in the U. S. Pharmacopeia,
it was decided to try extraction methods.[235] This in turn led to the
question of solubilities. The U. S. Pharmacopeia gives the solubility
of phenylcinchoninic acid only in general terms; hence it was deemed
advisable to determine its solubilities and describe them in more
definite terms. The sample of phenylcinchoninic acid employed to
determine the solubility was obtained by repeated recrystallization
from alcohol of a commercial specimen. Solubilities were determined in
water; 95.0 per cent. alcohol; 48.5 per cent. alcohol;[236] chloroform
and ethyl acetate.[237] Complete saturation of the solvent was attained
according to the U. S. P. IX method (p. 599). The bath was maintained
at a temperature of 25 C., with a range of ± 0.2 degrees. The solution
was analyzed by the method of Seidell.[238] The data obtained for the
solubility of phenylcinchoninic acid are given in Table 5.
TABLE 5.--SOLUBILITY OF CINCOPHEN
Gm. per Hundred Solubility,
Gm. of Parts by
Solvent Sat. Solution Weight
Distilled water 0.0160 1 in 6,216.0
95 per cent. ethyl alcohol 0.8343 1 in 119.0
Dilute ethyl alcohol 0.0875 1 in 1,142.6
Chloroform, 0.1075 1 in 929.7
Ethyl acetate 1.4151 1 in 70.6
[235] Attempts were made to make salts of phenylcinchoninic acid
with metals such as copper, mercury, barium and calcium, and also
the chloroplatinic acid or periodid addition products. Reliable
quantitative results could not be obtained.
[236] This corresponds to “diluted alcohol, U. S. P.”
[237] The ethyl acetate was Merck’s product (redistilled), stated to
contain 81.6 per cent. of ethyl acetate, 10 per cent. alcohol and
alcohol derivatives.
[238] Seidell, A.: Bull. 67, Hyg. Lab., U. S. P. H. S., p. 11.
The Abbott Laboratories, Chicago, have been licensed by the Federal
Trade Commission to manufacture cinchophen. Other firms, however, have
decided to manufacture it without the formality of obtaining a license,
evidently considering the German-obtained patent not to be valid.[239]
[239] Very recently the Chemical Foundation, Inc., has undertaken to
grant licenses for cinchophen. The Calco Chemical Company has obtained
one.
PROCAIN (NOVOCAIN)
Procain was introduced in medicine under the proprietary name
“novocain,” and before the war was obtainable in this country only
through the Farbwerke Hoechst Company, the American representative
of the German establishment, Farbwerke vorm Meister Lucius
Bruening, Hoechst a. M. Chemically it is the mono-hydrochlorid of
para-amino-benzoyl-diethyl-amino-ethanol, having the structural formula:
[Illustration: NH₂--(benzene ring)COO-CH₂-CH₂--N(C₂H₅)₂.HCl]
It is prepared according to U. S. patent No. 812554 (issued to Alfred
Einhorn, Munich, Germany) by treating para-nitro-benzoylchlorid with
ethylene chlorhydrin and diethylamin with subsequent reduction of the
nitro groups, the resulting product being purified by recrystallization.
Procain is employed largely in infiltration anesthesia. It is less
toxic than cocain, but its anesthetic action is not sustained. This
drawback is overcome by the simultaneous injection of epinephrin, and
for this reason procain is often compounded with epinephrin in tablets,
thus obviating the necessity of separate solutions.
When the first specimens of the American-made product were submitted
through the channels of the Federal Trade Commission, it was necessary
to compile a monograph.[240] This was prepared from descriptions in
the available literature, mostly from tests described in New and
Nonofficial Remedies, 1918, and the German Pharmacopeia V.
[240] The monograph appears in New and Nonofficial Remedies, 1919.
The submitted products were found satisfactory chemically. The toxicity
determinations made by Dr. R. A. Hatcher, with the assistance of
Dr. Carey Eggleston[241] indicated that none of the specimens are
to be considered dangerous when used in ordinary dosage for normal
individuals. Therefore the Federal Trade Commission, on recommendation
of the Committee on Synthetic Drugs of the National Research Council
(aided by the A. M. A. Chemical Laboratory), issued licenses for the
manufacture of procain to the Farbwerke-Hoechst Company (which license
was later transferred to the H. A. Metz Laboratories), to the Abbott
Laboratories, to the Calco Chemical Company and to the Rector Chemical
Company.
[241] The report of these and subsequent toxicity experiments on
procain appeared in the report of the Council on Pharmacy and
Chemistry, J. A. M. A. 72: 136 (Jan. 11) 1919.
Subsequently the products of the licensed firms were submitted to the
Council on Pharmacy and Chemistry, which in turn invoked the aid of the
A. M. A. Chemical Laboratory and the Cornell University Pharmacologic
Laboratory. Later the Council asked the laboratory to examine the
_market_ supply. Altogether, therefore, a number of products were
examined which were found to respond satisfactorily to the tests
outlined (Table 6).
TABLE 6
=============================================================
Date Melting Ash,
Brand Received Color Point, C.* %
Procain (Abbott), 12/21/17 White 154-155 None
from Committee
on Synthetic Drugs
Procain (Abbott), 1/29/18 White 153.5-154.5 None
submitted to Coun-
cil P. and C.
Procain (Abbott), 8/31/18 White 152.5-153.5 None
Gen. Pur. Off.
U. S. Army
Procain (Abbott), 9/30/18 Slight 153-154.5 None
Gen. Pur. Off. brownish
U. S. Army, tint
No. 89999
Procain (Abbott), 9/30/18 Slight 153-154. 0.005
Gen. Pur. Off. brownish
U. S. Army, tint
No. 89998
Procain (Abbott), 10/8/18 Slight 153-154 None
Gen. Pur. Off. brownish
U. S. Army, tint
No. 89997
Procain (Abbott), 11/4/18 Slight 153.5-154.5 None
Gen. Pur. Off. brownish
U. S. Army, tint
No. 89996
Procain (Abbott), 11/4/18 Slight 153.5-154.5 None
Gen. Pur. Off. brownish
U. S. Army, tint
No. 810995
Procain (Calco), 2/7/18 White 153.5-154.5 None
from Committee
on Synthetic Drugs
Procain (Farbwerke- 10/24/18 White 153-154 None
Hoechst Co.), sub-
mitted to Council
Procain (Farbwerke- 12/10/17 White 153-154.5 None
Hoechst Co.),sub-
mitted to Council
Procain (Farbwerke- 8/9/18 White 153.5-154.5 None
Hoechst Co.), sub-
mitted to Council,
market spec. “A 56”
Procain (Farbwerke- 9/9/18 White 153.5-154.5 None
Hoechst Co.), sub-
mitted to Council,
market spec. “A 57”
Procain (H. A. Metz 8/23/18 White 153-154 None
Lab.), market spec.
“A 63”
Procain (H. A. Metz 9/23/18 White 153-154 None
Lab.), market spec.
“A 57”
Procain (Rector), 12/18/17 White 153-154.5 None
from Committee on
Synthetic Drugs
Procain (Rector), 5/2/18 White 152.5-153 None
from Committee on
Synthetic Drugs
Procain (Rector), 8/20/18 Slight 153-155 None
market spec brownish
tint
Procain (Rector), 8/23/18 Slight 153-155 None
market spec brownish
tint
Procain (Rector), 8/23/18 Slight 153-154.5 None
market spec brownish
tint
-------------------------------------------------------------
* U. S. Patent 812,554--the novocain patent--declares that the salt
melts at 156 C. Evidently based on this, both the German Pharmacopeia
and past editions of New and Nonofficial Remedies give this melting
point. Two specimens of German-made novocain obtained from our files,
stated to be manufactured by Farbwerke-Hoechst vorm. Meister, Lucius
and Bruening, Hoechst a. M., were found to melt, respectively,
between 154 and 155 C. and between 153.5 and 154.5 C. when the
melting point was determined according to the direction of the U. S.
Pharmacopeia, ninth revision. The various specimens examined at that
time melted between 153 and 155 C., and it was decided to permit this
range.
An examination of some American-made procain-suprarenin tablets was
also made. The procain was determined by liberation of the alkaloid
with ammonia water, extraction with chloroform, evaporation of the
chloroform, dissolving the alkaloid in one hundredth normal sulphuric
acid solution and titrating excess acid with one hundredth normal
sodium hydroxid solution. The epinephrin was determined according to
the method employed by Seidell,[242] with slight modifications. The
tablets contained the claimed amounts of ingredients.
[242] Seidell: J. Biol. Chem. 14: 19, 1913.
THE SYNTHETIC DRUG SITUATION
Before the war, the American physician was literally bombarded with new
and wonderful (?) coal-tar synthetics, most of which were originated
in Germany. In fact, it seemed that if a by-product in the manufacture
of dyes could not be used for a dye per se, then a place might be
found for it in the ever increasing lists of medicaments. By clever
advertising and propaganda among physicians, an artificial stimulation
for coal-tar drugs was created which evidently yielded lucrative
financial returns. As a result of the war, it is interesting to observe
that of all the synthetic drugs imported into this country from Germany
and on which the American patents were controlled by the Germans (up
to the time of our entrance into the war), the demand was really
sufficient enough to warrant the commercial manufacture of only four
of them by American firms. Of course, a larger number of _nonpatented
drugs_, also imported from Germany, are now being made in sufficient
quantities in this country; many of the drugs in this class were never
patented or are the ones which have survived after the patent had
expired, such as acetanilid, acetphenetidin, and acetylsalicylic acid.
In view of the agitation to found an institute for cooperative research
as an aid to the American drug industry under the auspices of the
American Chemical Society, it will be well for the medical profession
to be on its guard against too enthusiastic propaganda on the part of
those engaged in the laudable enterprise of promoting American chemical
industry. Unless it is, it may be inflicted in the future, as in the
past, with a large number of drugs that are either useless, harmful or
unessential modifications of well-known pharmaceuticals. It will be
well also for the chemists--those engaged in this enterprise--to be
sure that the product is of therapeutic value before asking its use as
a medicine. The American medical profession has learned that relatively
few of the many German synthetics were really valuable or decided
improvements over established drugs. If American chemists desire
to retain their prestige with the medical profession, they should
earnestly endeavor to see that the advantages derived from the war and
from such an institute as proposed are not abused in the worthy desire
to popularize chemistry both educationally and commercially. They
should realize that physicians are in no receptive mood for a flood of
synthetics, even though “American-made.”
On the other hand, the constructive possibilities of chemistry in the
service of medicine should serve as a stimulus for American research.
Notwithstanding all the pharmaceutical shrubbery which Germany sent
to us, still it did contain some synthetics that were worth while.
As therapeutics has been benefited by these organic chemicals, it is
logical to reason by analogy that there remain other synthetics to be
discovered which will occupy places of equal distinction in the modern
materia medica. For example, vaccines are of undoubted merit in the
field of immunology, but their action is, in the end, chemical; as soon
as chemical technic is refined by medicochemical research, it is quite
possible that a definite chemical agent (synthetic) will supersede
the indefinite bacterial vaccine. Obviously the American chemist has
the opportunity of showing his resourcefulness in aiding the public
health of America and the world. In this connection, a cooperative
institute devoted to purely scientific drug research, and governed
in such a manner as to inspire confidence in its humanitarianism
and unbiased judgment, should serve a most commendable purpose.
The hopes of American men of science are for a monumental research
institution--cooperative with all the allied professions--and, as the
_Chicago Chemical Bulletin stated_, “Stripped of all professional
or commercial pettishness and not dominated by any one group of
scientists.”[243]
[243] Proposed Institute for Drug Research, editorial Chicago Chem.
Bull., April, 1919, p. 67.
CONCLUSIONS
As for the results of the work so far, they can be summed up in two
sentences.
1. American chemists are producing synthetic drugs formerly controlled
by Germany, and thus have declared their independence of German
chemicals.
2. Judging from the evidence at hand, we can feel assured that the
quality of American synthetics will be second to none.--(_From The
Journal A. M. A., Sept. 6, 1919._)
PART III
CONTRIBUTIONS FROM THE JOURNAL: PROPRIETARY PRODUCTS
NOSTRUMS IN RETROSPECT
A Series of Nine Articles Reviewing Worthless or Unscientific
Proprietary Mixtures Previously Criticized
S. Q. Lapius, M.D.
[FOREWORD.--It is more than twelve years since the Council on Pharmacy
and Chemistry of the American Medical Association was created. Since
then there have been but few issues of The Journal that have not called
the attention of the medical profession to the debasing influence
on scientific medicine of unscientific or worthless proprietary
mixtures advertised to physicians for their use in prescribing. The
Council on Pharmacy and Chemistry has investigated and shown many of
these preparations to be fraudulent in one way or another, and these
reports have been published in The Journal. In spite of this, these
preparations have been advertised continuously to physicians, through
medical journals and otherwise, and prescribed by a large number of
physicians. One reason for this is that there are many physicians who
have never seen these reports--who were not in active practice at the
time, or who were not reading The Journal. We probably have among our
readers at the present time 35,000 or 40,000 physicians who were not
among the readers of The Journal twelve years ago. It is desirable,
then, that we should take up, in more or less detail, several of the
more widely advertised products that have been the subjects of previous
reports. It has been repeatedly stated in The Journal that many of the
proprietary mixtures--the so-called ethical proprietaries advertised
to physicians--were no better and no worse than “patent medicines”
advertised to the public.
Every physician who has the welfare of medicine at heart should put
these questions squarely to himself if he has not already taken a firm
stand on this whole problem: What is my attitude toward the work of
the Council? Are its reports worthy of acceptance? Am I upholding the
Council in its efforts to place therapeutics on a rational basis, not
by blind faith alone, but by an honestly critical attitude toward it?
Am I following the path of indolence by taking the advice of nostrum
makers without any serious effort to determine whether they are true or
false? In a word, am I really practicing medicine, or am I an unpaid
agent and a dupe of nostrum makers? There are other revolutions than
political. The public can be wronged just as certainly by the abuse of
its confidence in clinicians as by the usurpers of political power, and
when the public is thoroughly aroused the heavy hand of retribution
is not likely to be too discriminating. That the sins of clinicians
are standing out plain for any one who wishes to read is becoming more
and more evident. There is but one short and ugly word that properly
characterizes the physician who accepts a fee for prescribing that
about which he has no more knowledge than has the one for whom he
prescribes it. Are you with the nostrum makers or with decent medicine?
The article below is the first of a series written for The Journal
by one who is thoroughly conversant with the work of the Council on
Pharmacy and Chemistry and can speak authoritatively on questions
dealing with the action of drugs and the treatment of diseases. We
believe that these articles will prove of interest and profit and that
they will help physicians to answer the questions just propounded.]
[ARTICLE I]
Bell-Ans (Pa-Pay-Ans Bell)[H]
[H] See also ????.{sic}
Bell-ans, for years advertised only in medical journals under the name
“Pa-pay-ans (Bell),” is now advertised in newspapers as a remedy that
“Absolutely Removes Indigestion.” As it is still being advertised to
physicians, we propose to analyze the claims made for it with as much
care as would be exercised in the discussion of the newest discovery in
medicine, because we believe that it is desirable to show the trend of
exploitation of a certain type of preparation in the medical press.
In the _New York Medical Journal_ the following advertisement recently
appeared on the front cover:
[Illustration:
+-------------------------------------------------------------+
| =Acute Indigestion= |
| |
| Yesterday a great soldier and today the head of a big trust |
| succumbed to an attack of Acute Indigestion, and every day |
| we hear from some physician of some case he has saved with |
| BELL-ANS by giving SIX (6) tablets dissolved in a glass of |
| hot water and repeating if necessary. Can any doctor who |
| reads this fail to provide himself with the free supply of |
| BELL-ANS which we will gladly send for his emergency case? |
| |
| Bell & Co. (Inc.) Mfg. Chemists Orangeburg New York U S A |
+-------------------------------------------------------------+
Typical of Bell-ans advertisements as appearing in medical journals.]
A recently purchased package of Bell-ans contained a circular in which
it was stated that Bell-ans removes flatulence, vertigo, weakness and
other symptoms of indigestion quickly and pleasantly; that it aids
the digestion of food and tends to restore the digestive tract to a
normal condition; that it relieves vomiting in pregnancy, alcoholism,
seasickness and cholera morbus, besides being pleasant, harmless and
effective for colic, sour stomach, feverishness, and wakefulness of
infants and children. The circular contained paragraphs purporting
to be taken from various medical journals, including the _New York
Medical Journal_, _Wisconsin Medical Recorder_, the _Lancet Clinic_,
_International Journal of Surgery_, and _Massachusetts Medical
Journal_. No exact references were given to permit verification or to
determine whether or not the quotations were from “reading notices”
(advertisements) or from the scientific part of the journals in
question. To quote one of the statements given:
“The results from the use of Bell-ans (Pa-Pay-ans Bell) in the
treatment of indigestion are so prompt and so generally good--and
the evidence of this fact is accumulating so rapidly and from such
reliable sources--that we venture to suggest to our readers who
have not tried this remedy that they prescribe one original sealed
package of Bell-ans (Pa-pay-ans Bell) and that they carefully note
the results from its use.
“We suggest an original sealed package because the preparation is
widely and badly imitated, and unless such a package is specified
an imitation of little value may be substituted and the experiment
be thus rendered useless.”
It is possible that Bell-ans has been imitated, but it is not true
that it is widely imitated, for no such imitation has ever been called
to our attention, and we strongly suspect that the main reason for
desiring that an original package be dispensed is that the patient may
see for himself the name BELL-ANS plainly blown in the glass.
The circular in question states that there is no derangement of the
digestive organs on which the proper dose of Bell-ans will not act
quickly and pleasantly! These are samples of the claims made for
Bell-ans. Let us inquire into the nature of the conditions for which
the preparation is recommended and the treatment advised by well known
clinicians.
The subject of indigestion is discussed by Robert Hutchison and Robert
Saundby under the general title of dyspepsia in the “Index of Treatment
by Various Writers,” Edition 6, 1912, pp. 260-265. Hutchison says:
“In the first place it must be remembered that in many patients who
complain of ‘indigestion’ the seat of the trouble is not in the stomach
at all.”
[Illustration:
+-----------------------------------------------------------------+
| A Philadelphia Doctor writes: |
| |
| “Your BELL-ANS for ingestion do just what you claim and more |
| too. I, personally, had a bad case of intestinal indigestion |
| with gastric vertigo. I had taken almost everything and got no |
| relief, until I commenced to take BELL-ANS--four to six tablets |
| in a large glassful of hot water after each meal. You have my |
| permission to use this statement, with my name and address if |
| you wish. I prescribe BELL-ANS constantly” |
| |
| =BELL-ANS= |
| FOR INDIGESTION |
| 25c package at every drug store in the U. S. |
+-----------------------------------------------------------------+
Newspaper advertisement of Bell-ans, capitalizing the statements of
physicians.]
The general principles to be observed in the treatment of functional
dyspepsia, as given by Hutchison, are: (1) to remove the cause; (2) to
adapt the diet to the impaired functional power of the stomach; (3)
to administer such drugs as are calculated to stimulate or correct
the particular function or functions which happen to be impaired,
or disordered. Proper diet, proper mastication of food, hygiene of
the mouth, and constipation are enumerated as deserving attention.
Careful attention to securing a proper diet is essential. The choice
of drugs depends, of course, on the conditions that give rise to
indigestion, and he calls attention to the necessity of avoiding all
routine treatment and compiling one’s prescription with an eye to the
special disorder or disorders of function, whether secretory, motor or
sensory, believed to be present. Hutchison gives the following typical
prescriptions to illustrate the use of drugs in the different disorders
of function:
FOR HYPERSECRETION (HYPERCHLORHYDRIA, ACID DYSPEPSIA, ETC.)
Sodium bromid 10 grains
Bismuth subcarbonate 15 grains
Chloroform water 1/2 ounce
This mixture to be taken before meals.
Sodium bicarbonate.
Bismuth subcarbonate.
Heavy magnesium carbonate, of each equal parts.
A small teaspoonful of the powder to be taken mixed with a little
water or milk about two hours after meals.
FOR DEFICIENT SECRETION (HYPOCHYLIA, ACHYLIA, GASTRITIS, ETC.)
Sodium bicarbonate 10 grains
Tincture of nux vomica 10 minims
Spirit of chloroform 8 minims
Compound infusion of gentian 1/2 ounce
This mixture to be taken before meals.
Dilute hydrochloric acid and glycerin, of each 15 minims with
enough water to make half an ounce, to be taken about twenty
minutes after meals.
FOR DEFECTIVE MOTILITY (ATONIC DYSPEPSIA, GASTROPTOSIS, ETC.)
Hutchison recommends the use of 10 minims of tincture of nux vomica
in an aromatic vehicle, such as infusion of quassia and compound
tincture of cardamom; but another aromatic bitter, such as the
compound tincture of gentian, will serve quite as well, of course.
This is to be taken before each meal, and for the flatulence that
often accompanies this trouble he gives menthol, aromatic spirit of
ammonia and spirit of chloroform, as may be needed.
FOR ACID DYSPEPSIA
Robert Saundby recommends the following to be used before each
meal for the relief of acid dyspepsia: sodium bicarbonate, bismuth
subcarbonate, magnesium carbonate, of each 10 grains; mucilage of
tragacanth 15 minims, and enough peppermint water to make an ounce.
These are only a few of the conditions that are discussed by Hutchison
and Saundby, but they serve to show that the treatment of indigestion
by a single prescription or combination is wholly irrational.
Bell-ans, both under its present name and under its older name,
“Pa-pay-ans (Bell),” has always been alleged by its manufacturers to
contain papain or to be a preparation of the digestive juice from
the fruit of _Carica papaya_ (papaw) with other substances. Various
chemists have attempted to find papain present and to determine the
digestive power of the tablets, but without success. For this reason
The Journal suggested that the change of name from “Pa-pay-ans (Bell)”
to “Bell-ans” was probably not made entirely for euphonious reasons,
as alleged, especially when one considers that the name of a nostrum
is its most valuable asset. It is much more likely that as analyses
indicated there was not and probably never had been any papain present
in the product, the name was changed for fear that some day the
misleading term “Pa-pay-ans” might bring the preparation in conflict
with the federal Food and Drugs Act.
Pa-pay-ans (Bell) was examined for the Council on Pharmacy and
Chemistry in 1909 and the tablets were found to consist of charcoal,
sodium bicarbonate, ginger, saccharin and oil of gaultheria. No
digestive ferment could be detected in the tablets. Sodium bicarbonate
is antacid and serves to dissolve mucus; ginger, if in sufficient
amount, causes the expulsion of flatus, and charcoal, while an
absorbent in the dry state, is probably useless for any therapeutic
purpose whatever after it becomes saturated with gastric juice.
Bell-ans, then, has all of the virtues, which are few, and all of
the limitations, which are many, of a tablet of sodium bicarbonate
and ginger. Its value in the treatment of acute indigestion would be
limited to the value of a tablet of such a composition. It is absurd to
suppose that it could have the slightest value in the far more serious
conditions attended with intestinal indigestion, with the toxemia and
autointoxication to which they give rise.
Bell-ans is now advertised directly to the public--but it is no less
valuable on that account. True, it is a “patent medicine” in the
commonly accepted sense of the term, but it is no more a “patent
medicine” today than it was fifteen years ago when it reached the
public, not through the direct medium of the newspapers but the more
indirect route of the medical journals and undiscriminating physicians.
It is true that, in view of the serious nature of many conditions
which are loosely spoken of by the public as “indigestion,” its present
method of exploitation is likely to make it just that much more
dangerous because of the larger publicity that will be given. The point
to be borne in mind is that Bell-ans is now in fact what it has always
been in essence, a “patent medicine.”
[Illustration:
+ - - - - - - - +
| BUSINESS NOTICE |
|
| BELL-ANS |
| Absolutely Removes |
| Indigestion. One |
| package proves it. |
| 25c at all druggists. |
+ - - - - - - - +
Typical of Bell-ans advertisements as appearing in newspapers.]
Again we ask the question: How do you wish to be classified,
Doctor--among those who follow blindly the lead of a firm of nostrum
makers, or among the intelligent members of the profession who study
their cases carefully and prescribe intelligently? The manufacturers of
Bell-ans claim that 100,000 American physicians now prescribe Bell-ans,
and that 600,000,000 of the tablets are sold annually. If this is
even approximately true it is a serious reflection on the medical
profession, for the Council examined Bell-ans and reported its findings
nearly eight years ago (_J. A. M. A._ =53=:569 [Aug. 14] 1909), and the
statements made in that report are as incontrovertible today as they
were then.--(_From The Journal A. M. A., Nov. 24, 1917._)
[ARTICLE II]
Anasarcin and Anedemin
“Anasarcin” and “Anedemin” are the twin nostrums of cardiac
pseudotherapy. They are dubbed “twin nostrums” not so much because of
any similarity in their formulas, that being a minor consideration
in the average nostrum, but because of the close similarity in their
methods of exploitation, the therapeutic claims made for them, and the
time and place of their birth.
It may be remembered that they both claim Winchester, Tenn., as their
birthplace, and they appeared on the market at about the same time;
furthermore, a comparison of the claims formerly made for both of them
indicated that one mind conceived the main idea that lies back of their
exploitation. While Anasarcin is especially dealt with in this article,
much of the discussion applies with equal force to Anedemin.
A LUSH FIELD FOR NOSTRUMS
Cardiac disease, with its resultant renal involvement, is frequently
encountered; and running, as it does, a chronic course, it offers an
almost ideal field of exploitation for the typical nostrum vender. By
a typical nostrum vender we mean one whose knowledge of his product
is far below that of his appreciation of a certain element of human
character. On this element rests the whole secret of the nostrum
vender’s success. It is variously termed credulity, gullibility and
childlike simplicity, but it is that which often causes even the most
conscientious clinician to turn aside from the use of the best known
and most dependable drugs at his command, in the face of disappointment
and failure, and employ some vaunted mixture which, in his saner
moments, he scorns to use.
Anedemin is said to consist of a “Scientific Combination of three of
the more recently investigated members of the Digitalis Series, with
Sambucus”; that is, of apocynum, strophanthus and squill with elder.
It is difficult to know just what idea the statement that it is a
“scientific combination” of these drugs is intended to convey, for
it is unscientific to mix three drugs of this group for use in fixed
proportion in a wide range of conditions, if indeed, there is ever any
indication for their use.
The great disadvantages of strophanthus and apocynum pertain to the
extreme uncertainty of their absorption from the gastro-intestinal
tract. Strophanthus is occasionally absorbed promptly, sometimes
so slowly that the therapeutic effects are not induced until an
amount equal to several times that which would prove fatal if all of
it were absorbed into the circulation has been administered, and,
unfortunately, one cannot control the absorption which may continue
until a fatal effect is induced. This is true to an even greater degree
of apocynum, and it was due to the recognition of this fact that
apocynum was not admitted to the U. S. Pharmacopeia IX, the committee
on dosage having agreed that no safe and effective dose could be given.
THE COUNCIL’S PREVIOUS FINDINGS
In 1907 the Council on Pharmacy and Chemistry examined the literature
used in the exploitation of Anasarcin and Anedemin and published its
report. Anasarcin tablets, it was pointed out, were said to contain
the active principles of _Oxydendron arboreum_ (sour wood), _Sambucus
canadensis_ (elder) and _Urginea scilla_ (squill), and the following
claims were made for the nostrum:
“Does what dropsy medicaments have hitherto failed to accomplish.”
“Superior to digitalis, strophanthus, scoparius, squills, acetate
of potash and the hydragogue cathartics all put together.”
“The only known relief and permanent cure of dropsies.”
“Unrivaled heart tonic.”
“The most powerful agent known.”
“Safe in administration.”
“Non-toxic as ordinarily administered.”
“Will nauseate some persons,” but “the reaction from the temporary
depression is prompt.”
“In Bright’s disease, both the interstitial and parenchymatous
forms of nephritis, acute or chronic, no remedy ... to equal it in
efficacy.”
“Without increasing the debility of the patient or interfering with
nutrition by producing loss of appetite ...”
“This treatment is to be continued without cessation until all
symptoms of dropsy have disappeared.”
A comparison of the earlier claims with those now being made (see
advertisement reproduced from the _New York Medical Journal_)
illustrates one of the results of the work of the Council. Today the
nostrum exploiter avoids the cruder forms of obvious misstatement, but
continues to make, by inference, claims that are equally misleading.
It will be observed in this case that a more cautious pen worded the
later advertisement, but there is still evident the intent to convince
the reader that Anasarcin is superior to the official drugs in the
treatment of cardiovascular diseases. The facts are that Anasarcin is
at best a dangerous remedy in the hands of the average clinician in
the treatment of such conditions, and its use is at all times to be
condemned.
No competent investigator has ever investigated the pharmacology
of sour wood (_Oxydendron arboreum_), and it appears to have no
therapeutic value other than that due to a slight acidulousness. Elder
(_Sambucus canadensis_) contains a trace of a volatile oil as its most
important constituent, according to the British Pharmaceutical Codex of
1911 (p. 908), but it is difficult to explain why a trace of volatile
oil should be considered important. Elder may be dismissed without
further consideration in connection with Anasarcin tablets.
THE PHARMACOLOGY OF SQUILL
This leaves only squill among the constituents of Anasarcin for
consideration. Sollmann (Manual of Pharmacology, 1917, p. 409) in
discussing the advantages claimed for squill over other drugs of the
digitalis group, says: “Dixon, 1906, points out that any superiority
is outweighed by its disadvantages: uncertain absorption; strong
gastro-intestinal irritation.” Squill was formerly used as an
expectorant and diuretic, the activity having been attributed to two
amorphous glucosids, scillipicrin and scillitoxin, but Ewins, 1911,
found these to be impure mixtures. A later investigator claimed to
have isolated two glucosidal agents from squill, but similar claims
have often been made only to be disproved later, and we know of
no confirmation of the claims regarding the isolation of any pure
principles from squill having any true typical digitalis action.
The statement quoted from Sollmann is accepted by practically all
pharmacologists, and we may say with certainty that squill is decidedly
inferior to digitalis in the treatment of cardiovascular, and
cardiorenal diseases, and certainly no active principles of squill were
known to the scientific world at a time that the remarkable claims were
first made for Anasarcin by an obscure pharmacist of Winchester, Tenn.
Indeed, if Anasarcin were all that it was claimed to be, its discovery
would have made Winchester as famous as a certain Wisconsin city was
said to have been made by a popular beverage.
It has been abundantly demonstrated, and it is now almost universally
accepted among well informed pharmacologists and clinicians, that all
digitalis principles exert the same kind of action on the heart after
they enter the circulation in effective doses, though they differ
to an extraordinary degree in the intensity of their action and in
their undesired sideactions, such as nausea and vomiting. When the
use of Anasarcin (squill) is followed by immediate improvement after
digitalis has failed, it merely shows that the dosage of digitalis
was insufficient or that it was discontinued and the squill mixture
was substituted before the full therapeutic effects of the digitalis
developed.
WHEN THE DIGITALIS GROUP IS CONTRAINDICATED
If the administration of a sufficient dose of digitalis is not followed
by improvement in the circulation, it shows that the heart is incapable
of responding to such treatment and the further use of any of the drugs
of this group is distinctly contraindicated. This is confirmed by the
experience of nearly every competent observer of digitalis therapy, and
numerous fatalities have resulted from the failure to appreciate this
fact and further administer some other member of the group, such as
strophanthus or squill.
It is now well known that the cardiac effects of toxic doses of squill,
and other members of the group, resemble closely those of cardiac
disease, and it is often impossible to determine whether the behavior
of the heart in a given case is attributable to insufficient dosage, to
excessive dosage, or to the progress of the cardiac disease itself. If
this occurs when one uses the best known members of the group, it is
certain that it occurs even more frequently when others that are less
understood are employed. In the light of this knowledge of the dangers
attending the incautious use of any member of the digitalis group,
and more especially the use of impure principles, such as are commonly
obtained from squill, it is impossible to condemn sufficiently the
recommendation that the use of Anasarcin should be continued without
cessation until all symptoms of dropsy have disappeared.
Digitalis bodies are not suited for the treatment of all cardiac
disturbances, and it is, of course, self-evident that a time must
come in the treatment of chronic cardiac disease when the heart is
incapable of responding to any form of treatment with improvement. But,
unfortunately, it never loses its response to toxic doses, and to push
the administration of any drug or mixture containing any drug of the
entire digitalis group--and especially those, like squill, in which the
side actions are most prominent--beyond the point of tolerance is to
court certain disaster.
THE TREATMENT OF CARDIAC DROPSY
While it is quite certain that many lives have been sacrificed to the
failure to understand this phase of cardiac therapy, it is equally
certain that many lives have been sacrificed because of insufficient
dosage, and one can steer a safe course between these dangers only by
using the best known preparation available; and in the present state
of our knowledge it is indisputable that digitalis and the tincture of
digitalis are best suited for the treatment of cardiac disease except
in those few cases in which intramuscular or intravenous administration
must be employed temporarily for immediate effect.
[Illustration]
The secret of prescribing successfully for the relief of dropsy in
cardiac disease consists in understanding the effects of digitalis
on the heart, in administering it until these effects indicate that
the desired object has been obtained, and stopping, or interrupting,
the administration at that point until the effects begin to wear off.
Cumulation, so called, is a positive advantage in such cases. It
merely means that the desired therapeutic effects once induced persist
for a time, and that further medication is unnecessary during such
persistence of action. Eggleston has recently shown (_Arch. Int. Med._
=16=:1 [July] 1915; abstr., _J. A. M. A._ =44=:459 [July 31] 1915) that
the full therapeutic effects of digitalis can be induced in suitable
cases within a few hours even with oral administration.
We are not aware of a single publication in which a careful, detailed
clinical study of Anasarcin has been reported. The claims made for
Anasarcin, past and present, indicate either a deliberate purpose
to mislead or crass ignorance of the rudiments of pharmacology and
therapeutics. The exploiters of the nostrum claim that thousands
of physicians have found Anasarcin tablets of unsurpassed remedial
value in the treatment of disorders of the circulatory system and of
ascitic conditions.[244] It must be admitted that too many physicians
have prescribed Anasarcin, otherwise the manufacturers would not have
continued to spend thousands of dollars in advertising it in medical
journals during a period of more than ten years.
[244] Former estimates of the number of physicians who prescribed
Anasarcin appear to have been too high, possibly based on the ratio
obtaining in Winchester, Tenn. Inquiry at five fairly busy drug stores
in a large eastern city showed that in no instance was the pharmacist
even acquainted with the name. One pretended to be, and manifested pity
for the inquirer’s ignorance in supposing that it could be imported
during the war! He was obviously merely less honest than the others,
who frankly admitted they had never heard of it.
Doctor, this article is meant to be a candid discussion with you,
whether you use Anasarcin or not, because every clinician is vitally
interested in the customs that obtain in the practice of medicine, and
we wish to put a hypothetic question to you. Answer it, at least to
yourself, in exactly the spirit in which it is put. Suppose that you
prescribe Anasarcin for a patient who is critically ill with cardiac
disease. He dies. Are you willing to tell the relatives frankly just
what you used and the nature of the evidence on which you based your
choice of this nostrum? Let the supposition be carried further and say
that the case was hopeless, and agree that digitalis and all other
drugs would have been equally ineffective. Granting all this, would
your explanation satisfy? Would you in all candor dare to offer such an
explanation? Try it as a hypothetic case before you are forced to apply
it.--(_From The Journal A. M. A., Dec. 8, 1917._)
[ARTICLE III]
Pepto-Mangan
It would be interesting, and even instructive, to know how many
educated physicians, if any, are now prescribing Pepto-Mangan (Gude):
interesting as indicating the number who have neglected to avail
themselves of the work of the Council on Pharmacy and Chemistry,
especially the earlier work; instructive in that it would show how many
are still prescribing by the rule of thumb, and who are taking their
therapeutic instructions from purely commercial sources instead of
striving to learn how to choose those drugs that are most effective in
the treatment of disease.
It has been pointed out many times in the pages of The Journal that
many nostrums are advertised first to physicians, and that after
physicians have served as the unpaid agents of the manufacturers in
introducing the preparations, their exploitation is then commonly
continued by means of advertisements in the public press. This plan has
been followed successfully in so many cases that we have now come to
look on it as the regular course. It is in keeping with this rule that
we find Pepto-Mangan now advertised in the public press, the physicians
having served the manufacturer’s purpose.
DISCARDED THEORIES OF IRON MEDICATION
It will be recalled that many years ago the theory was held that
hydrogen sulphid (sulphureted hydrogen) interfered with the absorption
of the iron of the food, and that the administration of medicinal
iron prevented this interference by neutralizing the hydrogen sulphid
(sulphureted hydrogen). It was only a short step to argue that
manganese might replace the medicinal iron in combining with the
hydrogen sulphid, permitting the food iron to be absorbed, and it
was held that only food iron could be utilized in the formation of
hemoglobin.
It is hardly necessary to remind the reader that this theory rests
on numerous fallacies. There is no hydrogen sulphid worth mentioning
in the small intestine where iron is absorbed; food iron cannot be
utilized directly in the formation of hemoglobin but must be broken
into simple forms for absorption; and, further, inorganic iron, such as
ferrous carbonate, serves the purpose admirably when iron is indicated.
With the acceptance of these well established facts, all possible
excuse for the therapeutic employment of Pepto-Mangan in place of iron
vanished; but as plain and simple as this fact is, the unnecessary and
expensive Pepto-Mangan continues to be prescribed by physicians who
will not take the slight trouble to investigate the claims for this
nostrum.
FALSE AND MISLEADING CLAIMS
There is not merely a difference of opinion between the exploiters and
the Council, but there has been also actual misrepresentation in the
exploitation of this nostrum to physicians. This has been shown on
more than one occasion. About twelve years ago, the M. J. Breitenbach
Company, the proprietors of Pepto-Mangan, claimed that the report of
the commission that had been appointed for the investigation of anemia
in Porto Rico “would alone suffice to establish Pepto-Mangan at once as
the foremost hematinic known.” Examination of the report showed that
the commission made no such claims; on the contrary the commission
protested against this misrepresentation (_J. A. M. A._ =45=:1099 [Oct.
7] 1905).
[Illustration: From the _New York Medical Journal_.]
Undaunted by this exposure of their methods, the Breitenbach Company
later sent out a statement of results purporting to have been obtained
by one Mateo M. Gillen, in the treatment of infantile anemia on
Randall’s Island in New York City. At the instance of The Journal
the hospital records in these cases were examined, and it was found
that the pretended report was little more than a tissue of falsehood
(_J. A. M. A._ =48=:1197 [April 6] 1907).
About two years ago the Council reported that while the statements
just referred to were no longer made, they had never been definitely
admitted by the Breitenbach Company to be erroneous, and that
Pepto-Mangan was then being exploited to the public indirectly.
(Council Reports, 1914, p. 121.)
We reproduce an advertisement that has been appearing weekly in the
_New York Medical Journal_ for several months. One can only suppose
that this advertisement was intended to mislead physicians, and it
would be an insult to the intelligence of the average reader to
attempt any detailed discussion of it, but enough has been said to
show how misleading the statements are. One should note particularly
the advice--old as the nostrum business itself--contained in the
advertisement, to prescribe an original bottle. The reason for such
advice is simple. Experience has shown that when original bottles are
dispensed patients soon learn to buy the nostrum without consulting the
physician, for they shrewdly suspect that he knows no more about the
preparation than they, and that he gets his information from precisely
the same sources that are available to them. They are obviously right.
In truth, the physician who prescribes Pepto-Mangan as a hematinic
shows ignorance of the most rudimentary facts of iron therapy, and the
intelligent patient soon perceives his limitations.
[Illustration: A newspaper advertisement of Pepto-Mangan.]
THE PROBLEM OF IRON THERAPY
The investigation of the problems of iron therapy and its utilization
in the formation of hemoglobin forms one of the most brilliant chapters
in pharmacologic research, and there is no better established fact in
therapeutics than that any organic or inorganic preparation of iron
that does not irritate the stomach may be employed effectively when the
administration of iron is indicated. “Useful Drugs” contains a list
of iron preparations that are suitable for all conditions which call
for iron, and the clinician may rest assured that he will never have
occasion to go outside that list to prescribe any substitute.
As a matter of fact, it seems probable that the very number of
available iron preparations has served to cause confusion, thus
affording an opportunity for the nostrum maker to introduce his
superfluous compounds. It may be difficult at times to select the
preparation of iron best suited to the individual patient; and it is
this difficulty that has led the clinician to listen to the seductive
claims made for the various pretended substitutes for iron. One
should approach the question of choosing the proper form of iron for
therapeutic use with the recognition of the fact that there is no
such thing as a substitute for iron in the formation of hemoglobin,
that there are no ideal forms of iron other than those found in the
foodstuffs. Further, the clinician cannot avoid the disadvantages
inherent in all forms of iron that he can prescribe, and he must
therefore seek that which seems best suited for the individual patient.
Bunge estimated the amounts of iron present in various foods; and a
table based on this, and other data, is given in “Pharmacology of
Useful Drugs” (published by the American Medical Association). Ordinary
foods in an ample diet contain enough iron to supply the normal daily
loss, which amounts to only a few milligrams, but many persons who
have poor appetites take an insufficient amount of iron in their food
and become anemic. In such cases the additional iron required can be
supplied best by adding spinach, eggs, apples, or other iron-rich food
to the dietary.
SOME IRON COMBINATIONS
William Hunter discusses the subject of anemia and its treatment at
considerable length in the “Index of Treatment,” Ed. 6, pp. 17-37,
and gives many prescriptions containing iron for use under different
conditions; and while it is unnecessary to reproduce all of these here,
a few may be given in order to suggest suitable methods of prescribing
iron when it cannot be given in sufficient amounts in the food.
In chlorosis Hunter advises that that form of iron which experience has
shown to be least disturbing to the patient’s stomach should be used,
and he suggests separate stomachic mixtures to be used simultaneously,
not mixed with the iron itself. When constipation exists--and this is a
very common accompaniment of chlorosis--he gives the following aperient
iron combination:
Gm. or c.c.
℞ Ferrous sulphate |25 gr. iv
Magnesium sulphate 4| Ʒ i
Aromatic sulphuric acid |5 ♏ vii
Tincture of ginger |7 ♏ x
Compound infusion of gentian (B. P.) q. s., ad 30| ℥ i
This, constituting a single dose, is to be taken twice daily--at
11 a. m. and 6 p. m. A little compound tincture of gentian and
water may be used in place of the compound infusion of the British
Pharmacopeia. He modifies this somewhat as occasion demands by using
sodium sulphate and adding sodium bicarbonate (which converts the
sulphate of iron into ferrous carbonate) and adds 10 minims of spirit
of chloroform to act as a stomachic.
Hunter also suggests the use of pills of aloes and iron in place of
the mixture described above, and when constipation has been corrected,
the aloes may be omitted and the pill of ferrous carbonate alone may
be used for the iron. Hunter’s comment regarding this pill is, “very
satisfactory.”
The same form of iron is available in the compound iron mixture,
formerly official, which Hunter says is exceedingly good. In this
country the compound solution of iron and ammonium acetate, Basham’s
mixture, so called, has long enjoyed a wide reputation as causing very
little disturbance of the stomach, and the homely tincture of ferric
chlorid is probably useful in a large majority of cases in which the
stomach is not especially irritable.
We may say with assurance that one of the forms suggested here
will suffice for practically every case in which it is necessary
to reinforce the amount of iron available in the food by some
pharmaceutical preparation. If these do not satisfy your requirements,
consult a really competent pharmacist and enlist his aid in devising
a mixture especially suited to your individual patient.--(_From the
Journal A. M. A., Dec. 29, 1917._)
[ARTICLE IV]
Cactina Pillets
This preparation may be considered briefly in view of the recent
discussion in this series of articles of the pharmacology of the
digitalis group and the principles of treatment in cardiovascular
disease. The manufacturers maintain that cactina is wholly unlike
digitalis, and that is the truth, as we shall show; but since they
claim that it is useful in certain conditions of the heart in which
digitalis is commonly employed by well informed clinicians, it is
necessary to consider its cardiac actions--or its lack of them! It is
difficult to determine just what action cactina is supposed to exert on
the heart. For example, one advertisement contains the following:
“Cactina Pillets. A gentle cardiac tonic that supports and sustains
the heart through its capacity to improve cardiac nutrition.”
Just how the cardiac nutrition is to be improved without an improved
coronary circulation is not explained. It would be interesting to know
in what other way this is to be accomplished, and how an improved
coronary circulation can be induced without acting on the heart or
vessels. But that is what digitalis does, and you should remember that
cactina is so very different from digitalis! Then again:
“Cactina Pillets. A remedy that steadies and strengthens the heart
by imparting tone to the heart muscle.”
That is a pretty direct statement, but digitalis imparts tone; and we
must not forget that “cactina” is wholly unlike digitalis, and we are
told that “cactina” is:
“Invaluable in all functional cardiac disorders such as
tachycardia, palpitation, arrhythmia, and whenever the heart’s
action needs regulating or support.”
If these are merely functional disorders of the heart, it is highly
desirable to know what are the symptoms of really serious cardiac
disease! Since the manufacturers give us no information concerning
the mode of action of “cactina” we will turn to the literature of
disinterested observers. If one attempts to discover the origin of
“cactina,” he will probably meet with disappointment, for various
bibliographies fail to mention the name of Sultan, who is said to have
isolated “cactina” from _Cactus grandiflorus_. It seems that Sultan
worked with _Cactus_, or some other plant, when a student of pharmacy,
and it is to be remembered that Cactina Pillets are manufactured by the
Sultan Drug Company.
It is doubtful whether Sultan actually worked with genuine _Cactus
grandiflorus_; and, in fact, there is good reason for thinking that
he did not, for all subsequent workers who have taken pains to secure
genuine _Cactus grandiflorus_ have failed to detect the presence of any
active principle, except possible traces that are of no therapeutic
importance whatever.
WHAT THE COUNCIL FOUND
The Council on Pharmacy and Chemistry examined the literature relating
to cactus and certain proprietary preparations, including Cactina
Pillets, alleged to be made from cactus, and has reported the results
of its investigation (_J. A. M. A._ =54=:888 [March 12] 1910) and we
will quote from that report.
“The therapeutic value of this plant has been variously estimated by
different observers. Experimental evidence as to its action is scanty
and no complete chemical examination has ever been made.
“Reputable men have testified that some of the plants of the cactus
family contain very active principles, but so far experiments seem to
prove that _Cactus grandiflorus_ has neither the action of digitalis
nor that of strychnin. The principal contributions, clinical and
experimental, for and against the drug are set out below.”
[Illustration: Typical advertisements of “Cactina Pillets” from the
Medical Record and New York Medical Journal, respectively.]
The report then proceeds to analyze the work of O. H. Myers, R. A.
Hatcher, Boinet and Boy-Teissier, Sayre, Gordon Sharp, S. A. Matthews,
P. W. Williams, Aulde and Ellingwood, and comes to conclusions that are
set forth as follows, in brief:
1. It is uncertain what part of the plant contains the active
principle, if any such principle exists.
2. Part of the experimental and clinical work has been published under
proprietary auspices.
3. The value of clinical evidence when unsupported by animal
experimentation is much diminished by the tendency of enthusiastic and
untrained observers to attribute to the drug given the effect really
due to general remedial measures, psychic suggestion and so forth.
In other words, the literature does not afford a report of a single
piece of careful painstaking work the results of which lend support to
the claims made for Cactina Pillets as stated above, for it is obvious
that if _Cactus grandiflorus_ contains no active principle, no active
principle can be extracted from it. Some time after the report of
the Council was published, Hatcher and Bailey secured genuine _Cactus
grandiflorus_ directly from a competent botanist, Dr. C. A. Purpus,
of Vera Cruz, Mexico, and studied it experimentally. They reported
(_J. A. M. A._ =56=:26 [Jan. 7] 1911) in part as follows:
“We have been unable to obtain any evidence that the true Mexican
_Cactus grandiflorus_ possesses any pharmacologic action whatever;
but, on the contrary, it appears to be a singularly inert substance
when administered either by the mouth or by the vein.”
When colossal doses of _Cactus grandiflorus_ are given by the vein,
they sometimes--but not always--appear to exert an extremely feeble
action on the heart; but this action is so slight that its nature
could not be determined. Even the most colossal doses of _Cactus
grandiflorus_ administered by the mouth to cats, dogs and frogs exert
no perceptible effect.
Sollmann thus satirizes the absurd claims made by the exploiters of
proprietary forms of cactus: “Should the heart be too slow, cactus
quickens it; if the heart is too fast, cactus slows it; should the
heart be too weak, cactus strengthens it; if the heart is too strong,
cactus weakens it; does the heart wobble, cactus steadies it; if the
heart is normal, cactus does not meddle with it” (_J. A. M. A._ =51=:52
[July 4] 1908).
Will physicians continue to accept the statements of an interested
nostrum vender--who submits not a shred of evidence to support his
claims, but who has a financial interest in convincing them--even when
his statements are diametrically opposed to all the evidence that the
Council on Pharmacy and Chemistry has been able to secure?--(_From The
Journal A. M. A., Jan. 19, 1918._)
[ARTICLE V]
Ammonol and Phenalgin
At the time that synthetic chemical drugs were coming into fame and
when every manufacturer who launched a new headache mixture claimed
to have achieved another triumph in synthetic chemistry, Ammonol and
Phenalgin were born. Of course, these twins of analgesic pseudotherapy
were claimed to be synthetics and were duly christened with “formulas.”
They were among the first of the nostrums examined for the Council on
Pharmacy and Chemistry, and the false claims made for them were exposed.
The analyses made for the Council showed that Ammonol and Phenalgin
were simple mixtures, having the following composition:
ACETANILID SODIUM BICARBONATE AMMONIUM CARBONATE
AMMONOL 50 25 20
PHENALGIN 57 20 10
The reports of the Council on, and numerous references to, these two
nostrums may be found in The Journal of various dates.[245] The reports
will prove interesting to those who are not familiar with, or have
forgotten, the methods of nostrum exploiters at the time the Council
was formed. Following the Council’s exposure of the false claims made
by the manufacturers of Phenalgin, the _Medical Record_ published an
advertisement of that nostrum in which an attempt was made to discredit
the Council’s report. The editor of the _Medical Record_ was requested
by the Council to publish the facts in the case but he refused to do so.
[245] J. A. M. A. 44: 1791 (June 3) 1905; ibid. 44: 1997 (June 24)
1905; ibid. 45: 935 (Sept. 23) 1905; ibid. 46: 134 (Jan. 13) 1906;
ibid. 46: 290 (Jan. 27) 1906; ibid. 58: 280 (Jan. 27) 1912.
Long after the death of Dr. Cyrus Edson, the claim was made that
Phenalgin was made under his direction and that it was his “discovery.”
As a matter of fact, Dr. Edson had favored the use of Ammonol at one
time, and when the Council exposed the false claims then being made
for Phenalgin, The Journal charged that a fraud was being perpetrated
on the medical profession. Despite the exposure of the methods used in
exploiting Ammonol and Phenalgin, one finds just as glaringly false
statements made in the advertisements of Phenalgin today as were
made in its unsavory past. This would seem to indicate either that
physicians have short memories or that they are strangely indifferent
to the welfare of their patients, to their own reputations and to the
good name of medicine.
The _New York Medical Journal_ of Dec. 22, 1917, contained an
advertisement of Phenalgin--it has been running for months--from which
the following is quoted:
“For the relief of PAIN the ‘logical supplanter of opium and
other habit-forming drugs’ is PHENALGIN. No matter how severe or
where located pain is promptly and satisfactorily controlled by
this effective anodyne--and without disturbing the digestion,
suppressing the secretions, causing constipation or inducing a drug
habit.
“This is why Phenalgin has superseded opium and its derivatives
for relieving HEADACHES, RHEUMATISM, GOUT, LA GRIPPE, LUMBAGO,
NEURALGIA, DISORDERS OF THE FEMALE, DYSMENORRHEA, AND PAINFUL
CONDITIONS GENERALLY. To thousands of physicians Phenalgin ‘is the
one dependable analgesic--the logical supplanter of opium.’”
If we are to suppose that the composition of Phenalgin is today
essentially the same as when it was examined, the claims just quoted
are obviously false for, of course, such a mixture must have the
properties of acetanilid with all of its drawbacks and limitations.
We may contrast the statements made in the advertisement just quoted
with those made in Bulletin 126 of the Bureau of Chemistry of the
U. S. Department of Agriculture. This bulletin on “The Harmful
Effects of Acetanilid, Antipyrin and Phenacetin” summarizes the
replies received from 400 physicians to whom a questionnaire had been
sent. The information thus gained was tabulated and the figures that
follow are from these tables. There were reported no fewer than 614
cases of poisoning by acetanilid with 16 deaths and 112 cases of its
habitual use. The larger number of cases of poisoning followed the
administration of the drug, by physicians, in doses larger than those
now regarded as fairly safe. This large number reported by only 400
physicians indicated an excessively large number in the whole country.
Since the questionnaire was sent to nearly a thousand physicians, of
whom about 500 failed to reply, it may be assumed that had it been sent
to the entire 130,000 physicians in the country, at least 75,000 cases
of poisoning would have been reported.
Prior to the passage of the federal Food and Drugs Act (the “Pure
Food Law”) many nostrum makers had declared that their preparations
contained no acetanilid. When that law went into effect, some of these
manufacturers triumphantly pointed to the fact that they were still
able to make the same claim without conflicting with the requirements
of the law. This was accomplished in fact by changing the formula and
substituting acetphenetidin (phenacetin) for the acetanilid. While
acetphenetidin is somewhat less toxic than acetanilid, bulk for bulk,
the toxicity and therapeutic activity of the two drugs are nearly
proportional.
The claim made by many proprietary medicine manufacturers that they are
“strictly ethical” because they advertise only to physicians is mere
verbal camouflage. There may be no more certain way of insuring the
continued use of a nostrum by the public than to have it prescribed by
physicians; and none know this better than the makers of nostrums. A
proprietary individuality is obtained by giving some special form to
the tablets and package or a special coloring to the capsules (“Specify
‘Phenalgin Pink Top Capsules’”) so as to indicate the identity of the
products in such a way that the patient may in the future procure them
without the advice or warning of the physician. When a proprietary
preparation with the name or initials stamped on it or attached to
it is prescribed, the patient immediately is aware of the fact, and
his respect for the physician’s intelligence and wisdom is naturally
lessened.
The physician should never place such dangerous drugs as acetanilid and
acetphenetidin, or ready made mixtures of them, in the hands of the
patient in such a way that they can be employed without his supervision
or control. He should never prescribe more than is needed at the time
and should not form the habit of using fixed doses or combinations
of drugs without a special reference to the particular needs of the
individual.
Certain forms of headache yield more readily to a mixture of caffein
and acetanilid or caffein and acetphenetidin than to either acetanilid
or acetphenetidin alone. When the physician wishes to prescribe such
a mixture he may combine 1 grain of caffein or 2 grains of citrated
caffein with 3 grains of acetanilid or 4 grains of acetphenetidin in
a powder or capsule. Under supervision such a dose may be repeated
at intervals of from two to four hours if necessary to control pain.
It is necessary to remember, however, that when small doses fail to
give relief, increase in the dose is useless. This fact is especially
important, and disregard or ignorance of it has been responsible for
many cases of poisoning. Further, it should be remembered that while it
was taught for many years that the admixture of caffein with acetanilid
lessened the effect of the latter drug on the heart, Hale has shown
that this is not the case and such mixtures must be used with special
caution.--(_From The Journal A. M. A., Feb. 2, 1918._)
[ARTICLE VI]
Fellows’ Syrup, and Other Preparations of the Hypophosphites
We hope that it is clear to those who have read the several articles
of this series that their purpose is to present evidence that will
enable the reader to form a correct estimate of the literature
employed in the exploitation of various nostrums. The distinction
between mere assertion--however plausible, and from however eminent
an authority--and evidence should again be emphasized. Satisfactory
evidence rests on careful observation by those who are capable of
accurately determining to what extent any changes that may be observed
are due to the therapeutic agent employed and not mere accompaniments
of such treatment.
When the Council on Pharmacy and Chemistry was organized in 1905,
the greater part of the literature of the nostrums was so palpably
misleading, the statements often so ludicrously false, that it was only
necessary to call attention to this fact to have those claims collapse.
As a result of the Council’s work, the exploiters of worthless nostrums
have developed a greater degree of shrewdness in avoiding the easily
exploded falsehoods. This has made it increasingly difficult to point
out the exact statements on which many of the false claims now rest,
even though the exploitation as a whole is as inherently dishonest as
before. If a nostrum is worthless, any exploitation must be false and
misleading in effect, even though not one single false direct statement
is made.
A platitude may be given an appearance of importance if uttered in an
impressive manner, and it may be employed to suggest far more than it
categorically affirms. These two facts are appreciated by many nostrum
exploiters and we find that they have adopted the impressive manner to
secure attention, and the platitude to suggest far more than they could
defend in direct statement. Thus we have the “lie with circumstance.”
FELLOWS’ SYRUP
A full page advertisement, which has been appearing regularly for
about a year and which must represent a good deal of money, is used to
give an appearance of importance to a few words which, if printed in
ordinary type, would either pass wholly unnoticed or would lead one to
assume that something essential to the full meaning had been omitted.
The statement, in full reads:
“Fellows’ Syrup differs from other preparations of the
hypophosphites. Leading clinicians in all parts of the world have
long recognized this important fact. Have you? To insure results,
prescribe the genuine ℞ Syr. Hypophos. Comp. Fellows’. Reject cheap
and inefficient substitutes. Reject preparations ‘just as good.’”
The only direct statement contained in the advertisement is to the
effect that many clinicians have observed that Fellows’ syrup and other
preparations of the hypophosphites are not alike. In truth, Fellows’
is not like the better preparations of this type, since after standing
it contains a muddy looking deposit that any pharmaceutical tyro would
be ashamed of. Technically, then, the statement is true, but it is
hardly credible that the manufacturer is paying for an entire page in a
medical journal to make this statement without any attempt to suggest
something else.
The advertising pages of six medical journals were examined in the
order in which they chanced to come to hand. In five of these, the
entire advertisement of Fellows’ syrup was in the words just quoted;
not a single word more. In one there was the further statement:
“Not a new-born prodigy or an untried experiment, but a remedy
whose usefulness has been fully demonstrated during half a century
of clinical application.”
These advertisements show that the exploiters of Fellows’ Syrup are
spending a great deal of money to induce physicians to prescribe the
preparation, and it is equally evident that they wish to convey the
impression that the preparation has some therapeutic value. Since we
find nothing directly false, in the first mentioned advertisement at
least, we must take the evident intent for consideration and determine
what therapeutic value, if any, this preparation has, and whether it is
advisable for physicians to employ it in any case.
The preparation, according to the statement just cited, has been in
use for fifty years. As the exploiter of any preparation cites the
most convincing evidence in his possession in support of his views,
this claim may be assumed to be the strongest available, and if this
evidence fails we must reject the contention as not proved. Here
we face a dilemma, for examination of the literature used in the
exploitation of Fellows’ Syrup fails to disclose any evidence of the
kind that we have described as satisfactory; and we are, therefore,
forced to conclude that none has ever been found. By this it is not
to be implied that no reputable physician has ever reported favorably
concerning the therapeutic effects of this preparation. It is quite
possible that an extensive literature of that sort might be found if
one examined the older medical journals. But the day has passed when
every improvement that follows the administration of a preparation is
blindly attributed to the drug in question. Clinical research today is
far more exacting.
We will assume that the reader who has investigated the question with
an open mind will have come to the decision that the contention that
Fellows’ syrup is of especial therapeutic value is not proved. We might
rest with that assumption and ask the clinician whether he is prepared
to use a nostrum that has been before the medical profession for half
a century without any satisfactory evidence having been gained that
it possesses therapeutic value. We might ask him whether he would be
willing to tell his patients that he was prescribing such a nostrum
for them in the face of the absence of any such evidence of its value.
THE INERTNESS OF THE HYPOPHOSPHITES
But we prefer to go even further and show him that not only is there
an entire absence of any evidence of its therapeutic value so far as
we have been able to learn, but in addition there is an abundance of
evidence that the hypophosphites are devoid of any such therapeutic
effect as they were formerly reputed to have, and that, in fact,
they are, so far as any effect based on their phosphorus content is
concerned, singularly inert.
While we have thus far taken the Fellows’ preparation as the subject
of the discussion, we may take a broader view and examine the subject
of the hypophosphites in general, and the substitutes containing
phosphorus that have been introduced from time to time. It hardly needs
to be said that if the hypophosphites are without therapeutic value, it
is impossible to give them value by combining them in a muddy-looking,
ill-made preparation such as Fellows’ Syrup. Such evidence was
submitted to the medical profession in a report of the Council on
Pharmacy and Chemistry (_J. A. M. A._ =67=:760 [Sept. 2] 1916); and we
would strongly advise any one who is disposed to act on the suggestion
contained in the advertisements of Fellows’, and other hypophosphite
preparations, to read that report in full and to think the matter over
before prescribing one of these nostrums. Quoting briefly from the
report in question:
“Although the overwhelming weight of evidence was against the
probability that the hypophosphite preparations are of value as
therapeutic agents, the Council thought it well to investigate the
subject. Dr. W. McKim Marriott of Baltimore was therefore requested
to review the evidence for and against the therapeutic usefulness
of the hypophosphites and to conduct such experiments as seemed
necessary.”
The Council was not content to rest on the mere absence of evidence
for the value of these preparations or any one of them, but sought
to obtain evidence that would fulfil the conditions mentioned above,
and in pursuance of this plan it secured the cooperation of a trained
investigator, one who would work under the best of conditions for
learning the truth. The results of Dr. Marriott’s investigation were
published in The Journal, Feb. 12, 1916, p. 486, and should be read by
everyone who has any interest in the problem. Lest some of our readers
may fail to refer to the original of Marriott’s paper, we will quote
briefly from it:
“None of the subjects of the experiment experienced any effect
whatsoever from the administration of the drug ... Almost all of the
ingested hypophosphite is eliminated unchanged....
“These experiments (Forbes) demonstrate conclusively that the
hypophosphites possess no specific value as a source of phosphorus
for the body.... It is doubtful if there are any conditions in which
the body suffers from lack of phosphorus. Even should such conditions
exist, phosphorus, in the form that it occurs in the ordinary foods,
or as phosphates, is more efficient in supplying the deficit than
hypophosphites that must be oxidized before utilization and which are
only about 15 per cent. oxidized if at all. For example, half a glass
of milk contains more available phosphorus than three large doses of
hypophosphites of 15 grains each, as great a dosage as is usually
given.
“What then, is the therapeutic value of hypophosphites? There is no
reliable evidence that they exert a physiologic effect; it has not
been demonstrated that they influence any pathologic process; they
are not ‘foods.’ If they are of any use, that use has never been
discovered.”
The case seems to stand about like this: A nostrum maker spends
thousands of dollars to tell physicians that his cloudy preparation is
not like other preparations, and physicians are expected to accept
that as convincing evidence that they should prescribe and their
patients, perforce, take it. This too, in spite of the evidence gained
by careful scientific investigators that the hypophosphites in fairly
large doses contain less available phosphorus than half a glass of
milk, and that there is no evidence available that they exert any
therapeutic effects at all.
Should we take the meaningless statement of a nostrum maker, who does
not submit evidence of any therapeutic value of his preparation--unless
one can call certain careless habits of prescribing evidence--and
assume the responsibility of prescribing a nostrum that according to
all scientific evidence available is useless, and of no more effect
than a few teaspoonfuls of milk, so far as its hypophosphite content is
concerned? It may be argued that it possesses some value because of its
bitter nature. We will not deny that it is bitter; so is strychnin, so
is quinin, so are scores of simple drugs, but what physician would care
to admit to his patients that he did not know how to prescribe a simple
bitter, such as nearly every layman can select for himself, without
recourse to a preparation such as Fellows’ Syrup?
We have felt that it is not wholly satisfactory to discourage the use
of a given nostrum without making an effort to assist the physician in
choosing wisely in the treatment of the condition for which the nostrum
is claimed to be useful. In the present instance, however, we fear that
would prove a task beyond our powers, for the hypophosphites have been
used in such a variety of conditions that the discussion would have to
include nearly the whole materia medica if we were to follow our usual
procedure.--(_From the Journal A. M. A. Feb. 16, 1918._)
[ARTICLE VII]
Shotgun Nostrums
Formerly it was customary to prescribe mixtures of many drugs on the
assumption that if one of the ingredients missed the mark another
might be expected to hit it, just as a poor marksman is more likely
to hit a target at short range with a blunderbuss than with a high
powered rifle. Increased precision in every branch of science has
become the outstanding feature of civilization. The soldier today
must shoot straight with a rifle that sends a single ball. There is
none of the disposition to rely on chance as when the blunderbuss was
used. A capable physician directs his drug straight at the seat of the
trouble, and we now have many drugs that can be depended on to exert
definite actions. The complex mixture is just as preposterous in modern
therapeutics as the blunderbuss would be on a modern battlefield.
Every drug exerts undesired side actions, and it is the aim of the
modern physician to try to select the one which will have a maximum of
therapeutic with a minimum of undesired actions. When a complex mixture
is employed, it is obvious that only the best is utilized, whereas all
the undesired side actions come into play. We do not pretend that even
the best studied drug has not much to be learned about it; but the
nostrum maker who exploits a complex mixture either knows practically
nothing of the side actions that it will exert, or, if he knows, he
conceals that knowledge. He knows that massive doses of hydrated
chloral combined with various narcotics can be relied on to cause
unconsciousness in nearly all cases, but he prefers to speak of this
as a hypnotic action. This is plain gambling with human life. When the
patient dies, it is difficult to prove that death was caused by the
mixture alone.
The Council on Pharmacy and Chemistry has expended a great deal of time
and energy in combating the “shotgun” nostrum evil. It is easy to
understand the disadvantages of such mixtures but it is not so easy to
demonstrate the misleading character of the claims made, with an entire
disregard of the truth, for these mixtures. No one believes that a pot
of gold lies at the end of the rainbow, but no one has actually gone
there to see for himself.
BROMIDIA
There are many types of “shotgun” nostrum. Some are dangerous,
as in the case of “Bromidia”; some are preposterous, therapeutic
monstrosities which excite the contempt of educated physicians, as in
the case of “Tongaline”; some are merely useless mixtures of well known
drugs, sold under grotesquely exaggerated claims, as in the case of
“Peacock’s Bromides.”
Various formulas have been given for Bromidia. The manufacturers appear
to be more cautious under those circumstances in which falsehood might
lead them into collision with the federal authorities, than when giving
reign to fancy and considering only the best means of winning the favor
of the physician. It is said to consist of hydrated chloral, potassium
bromid, Indian cannabis, and hyoscyamus. It is impossible to determine
from the published formulas just how much hydrated chloral and
potassium bromid it contains, but is probable that there are about 15
grains of each of these two drugs to the fluidram, and variable amounts
of Indian cannabis and a small amount of either extract or tincture of
hyoscyamus.
This much is certain: Bromidia is a distinctly dangerous mixture for
indiscriminate use. The claim of the manufacturers, implied, rather
than directly stated, that it is superior to an extemporaneously
prepared mixture of those drugs is especially reprehensible because it
tends to create the impression that the nostrum is safer in effective
doses, conducing to a false sense of security on the part of those
who are deluded into prescribing it in larger doses than they would a
mixture of the same drugs prepared extemporaneously.
A report of the Council on Pharmacy and Chemistry published in The
Journal, May 16, 1914, p. 1573, mentions three instances in which death
is reported to have followed the use of Bromidia. The manufacturers
of Bromidia have no magic power to render hydrated chloral harmless,
while it retains its hypnotic action. It depresses the central nervous
system, and it is nothing less than monstrous for any one to pretend
to rob this drug of its dangerous properties while it retains its
hypnotic effects. If the patient requires a hypnotic, the physician
should choose that one which his judgment and experience dictate as
the best for that particular patient. If he needs hydrated chloral,
the physician should prescribe exactly as much as he believes the
patient needs. If the effect is slightly greater or slightly less than
anticipated, no harm is done and the physician has gained experience
that will be valuable in future prescribing. If Bromidia is prescribed
and unexpected effects are induced, it is impossible to know whether
these were due to the hydrated chloral or to one of the other narcotics
or to a synergistic action; and there is nothing to guide in the
further use of the nostrum, for mixtures of narcotics commonly have
much less uniformity of action than a single drug.
The irritant action of hydrated chloral on the stomach can be avoided
by the use of bland fluids or dilute solutions. The following serves as
an example of the way in which it may be prescribed conveniently:
Gm. or c.c.
Hydrated chloral 2|6 gr. xl
Syrup of orange peel |
Water of each 30| fl ℥ i
A tablespoonful (15.0 c.c.) of this mixture, containing 10 grains
(0.65 gm.) of hydrated chloral, will often induce sleep in the absence
of severe pain or serious disturbance, and seldom does this dose have
to be repeated more than once in such simple cases. Hydrated chloral
is often used in somewhat smaller doses in combination with potassium
bromid, which may be prescribed in a mixture such as the following:
Gm. or c.c.
Hydrated chloral 1|3 gr. xx
Potassium bromid 3|9 gr. lx
Syrup of orange peel |
Water of each 30| fl ℥ i
In producing sleep when severe pain is absent this is as effective as
the preceding, in similar doses. The use of repeated doses of hydrated
chloral in such a mixture as this, or in the form of Bromidia or other
nostrum when sleeplessness is due to severe pain is highly dangerous.
It should be remembered that while hydrated chloral is an effective
hypnotic in case of simple sleeplessness, it is not actively analgesic
except in distinctly dangerous doses. Bromidia in repeated doses will
induce sleep even in the presence of pain, of course; but any active
narcotic does that, and it is correspondingly dangerous. Small doses of
morphin given alone are preferable when sleeplessness is due to severe
pain.
TONGALINE
“Tongaline” is an example of the type of “shotgun” nostrum that
would be merely ludicrous if we could look on anything that degrades
therapeutics so lightly. A report was made to the Council on Pharmacy
and Chemistry, and published in The Journal, July 17, 1915, p. 269, and
in this report it is stated that Tongaline is said to consist of tonga,
cimicifuga racemosa, sodium salicylate, colchicum, and pilocarpin.
Whether the formula was cut short just there because the office boy
ran out of breath at that point, or because the discoverers of this
wonderful combination had not heard of the eminently potent substances
that the witches added to their cauldron, we can leave to the reader’s
imagination, for it is manifestly impossible to present an orderly
discussion of the pharmacology and therapeutics of such a preposterous
jumble of drugs.
PEACOCKS BROMIDES
“Peacock’s Bromides” belongs to a slightly different class. It is said
to consist of the bromids of sodium, potassium, ammonium, calcium and
lithium. In the absence of a logical explanation of the pretended
superiority of this mixture over one that is made extemporaneously, the
exploiters seem to have been driven to the necessity of pretending that
its freedom from contaminating chlorids explains its claimed advantages
over mixtures of the official or commercial bromids. The truth is that
the chlorids are used as antidotes in bromid poisoning.
Disregard the claims made for Peacock’s Bromides, and ask yourself the
question whether you have ever actually seen any ill results following
the use of the official bromids that you could reasonably attribute to
contaminating chlorids. Furthermore, carefully consider the relative
advantage of a single bromid (say the bromid of potassium, or bromid
of sodium, if you prefer it), with the opportunity of observing its
effects and adjusting the dose in accordance with the results of your
experience, and a mixture such as Peacock’s Bromides, the composition
of which you do not know, and which the manufacturer can alter to suit
his own convenience.
While it is true that the therapeutic art will not degenerate in its
entirety merely because some physicians continue to use the most
fraudulent and worthless nostrums, yet, on the other hand, to the
extent that a physician continues to be guided by the false teachings
of nostrum venders who have no therapeutic training, he is plunged into
therapeutic chaos.--(_From The Journal A. M. A., March 2, 1918._)
[ARTICLE VIII]
Tyree’s Antiseptic and Aseptinol
It may seem paradoxic to say that recent progress in the medical
sciences has made therapeutic chaos possible, but it is true
nevertheless. Revolutions are sometimes slow and orderly, sometimes
sudden and attended with confusion. The revolutionary changes in
the medical sciences have been so numerous and so rapid that the
general practitioner has been unable to keep pace with them, and in
the resulting confusion the nostrum maker has seen his opportunity
for exploiting his useless, dangerous or unscientific preparations.
The greater the confusion, the greater his opportunity; and it is
no exaggeration to say that he has been the most potent factor in
maintaining the chaos of therapeutics.
The majority of our readers would probably say that the existing
scientific medical literature insures the permanence of established
beliefs, but every one who has delved into the literature has found
instances of truths that had been established and forgotten--buried
under the ever-increasing avalanche of contributions to that literature.
[Illustration: Typical half-page Tyree advertisement appearing in
medical journals.]
Rapid advances are still being made in the medical sciences and unless
constant vigilance is exercised therapeutics will return to the chaotic
condition from which it has so recently emerged. It was in recognition
of these facts--the danger of this return to chaos, and the difficulty,
in fact, impossibility, of any individual’s keeping pace with all of
the medical sciences--that the American Medical Association secured
the cooperation of men in various branches of medicine in the Council
on Pharmacy and Chemistry, in order that it may place the results of
therapeutic progress before the readers of The Journal in an impartial
manner.
Are you profiting by this work, or are you still depending on your
unaided efforts to distinguish the false teachings of the nostrum
venders from that of scientific medicine? Are you prescribing
“Antikamnia” and “Ammonol” or a simple member of the group, such as
acetanilid or phenacetin? Are you depending on “Tyree’s Antiseptic,”
so called, or are you using an antiseptic about which there is no
mystery, for which no false claims are made, and one which is really
effective? In short, are you using drugs of unquestioned value, such
as are described in “Useful Drugs,” or are you taking your therapeutic
instructions from nostrum makers’ circulars?
Perhaps you have been led to believe that the Council on Pharmacy and
Chemistry is composed of “theorists” and that the nostrums represent
the work of “practical men.” Every one should strive to be practical,
of course, and it is worth while to inquire whether scientific
experimenters, who so largely mold medical literature, should be termed
theorists, or practical men. A practical man practices that which is
useful in the treatment of the sick, and he must determine who is
capable of furnishing him with a better materia medica. A perusal of
medical literature will convince any unbiased mind that medical science
progresses only by means of experiment, hence experimenters must be
considered the really practical men while those who cling to outworn
theories are really the “theorists.”
[Illustration: Typical Aseptinol advertisement.]
When Lister introduced antiseptic methods into surgery he inaugurated a
veritable revolution, which afforded the nostrum makers opportunities
for reaping rich harvests through the exploitation--under extraordinary
claims--of cheap mixtures of little, or no, value. There is no lack
of antiseptics of extraordinary activity in the test tube that are
practically harmless to man, and it would seem natural to suppose that
such antiseptics could be used to control the development of bacteria
in such diseases as typhoid fever, but, unfortunately, such hopes have
not been fulfilled. Ehrlich experimented with many phenol derivatives
that showed decided antiseptic activity in the test tube, in the hope
that he might find some that could be used to combat such common
diseases as diphtheria and typhoid fever, but while many of these are
of low toxicity for man, he was unable to find even one that could
be used effectively in the treatment of any of these diseases. His
discovery of arsphenamin (“salvarsan”) resulted from quite another type
of investigation.
Many practitioners lose sight of the essential difference between
antiseptics and disinfectants and employ antiseptics in cases in which
only a disinfectant action would be of value. An antiseptic does not
destroy bacteria, it merely inhibits their growth; and when it is
diluted too much, it loses its effects and the bacteria may begin to
multiply as though no antiseptic had been used. This is especially
true after the use of weak antiseptics in the mouth. These are soon
diluted or removed by the saliva, and the bacteria continue to multiply
with only a momentary interruption at best; hence to advise the use
of an oral antiseptic as an effective means of treating diphtheria is
little short of criminal.
“Tyree’s Antiseptic Powder” was submitted to the Council nearly twelve
years ago. The label on the package stated:
“This preparation is a scientific combination of borate of sodium,
alumen, carbolic acid, glycerin and the crystallized principles of
thyme, eucalyptus, gaultheria and mentha in the form of a powder.”
[Illustration: One of the older newspaper advertisements of Tyree’s
Antiseptic Powder.]
A leaflet issued several years ago by the Aseptinol Manufacturing
Company states that “Pulv. Aseptinol Comp.” combines in an elegant form
boric acid, the salts of aluminum, crystallized phenol, and the active
crystalline principles of thymus, mentha and gaultheria.
A comparison of these formulas would justify the designation of the
two preparations as twins, but even one twin may have a wart where
the other lacks it. The formula of Pulv. Aseptinol Comp. given in the
leaflet also includes _Hydrastis canadensis_, but we believe that a
wart should be quite as much of an addition to the anatomy of man as
the hydrastis is to this already preposterous formula. Similar as the
formulas of these two nostrums were said to be, the general methods of
exploiting them were even more similar. A partial list of the diseases
for which each has been recommended by its exploiters shows the
similarity of methods pursued:
TYREE’S WAS SAID TO BE USEFUL PULV. ASEPTINOL COMP. WAS SAID TO
IN THE TREATMENT OF: BE USEFUL IN THE TREATMENT OF:
Leucorrhea Leucorrhea
Gonorrhea Gonorrhea
Vaginitis Vaginal inflammation
Pruritus Pruritus
Ulcerated conditions of Ulceration of vagina or
the mucous membrane cervix
Scrofulous ulcers Chronic ulcers
Syphilitic ulcers Prophylactic against
specific disease
Disinfecting offensive Cleansing pus cavities
cavities
Deodorant Deodorant
Profuse and offensive Checks abnormal secretion
perspiration
We stated that the formula furnished by Tyree was that given above, but
the Council was never able to learn when Tyree actually employed the
formula except for advertising purposes; and analysis of the powder
showed that Tyree’s Antiseptic Powder was essentially a mixture of
boric acid and zinc sulphate, with insignificant amounts of odorous
principles.
A remarkable fact brought out in the course of the consideration of
the preparation by the Council was that Tyree admitted that he had
changed the formula without having published the new one. The Council
then showed that a specimen of the “antiseptic” that had been kept in
a retail drug store for several years was essentially similar to that
sold at the later date. Thus it would seem that Mr. Tyree had been
making his powder by one formula and publishing an entirely different
one for years before the Council published the facts in the case.
If Tyree found it necessary to change the formula of his powder--if
indeed, he ever used the published formula--why did the Aseptinol
Manufacturing Company adopt it, or one so closely resembling it?
It is obvious that both of these twin nostrums are utterly unfit
for treating the various conditions for which they are or have been
recommended; and in view of the misrepresentation in one case, it
is difficult to understand why it should be taken as the model for
the other. Do physicians believe that a simple mixture of boric acid
and zinc sulphate, or a mixture such as that given in the formula of
“Aseptinol” powder, is in any way superior to a prescription such as
any physician could write?
There is a far more important question to consider than the relative
merits of such nostrums and a prescription of the physician’s own
devising. That question is whether the medical profession is going
to help perpetuate the chaotic conditions that the use of such
nostrums fosters or to assist in therapeutic progress by maintaining
its independence of such false teachers, and seeking to aid in the
establishment of a rational use of drugs and remedial measures.--(_From
The Journal A. M. A., March 30, 1918._)
[ARTICLE IX]
Neurosine and the Original Package Evil
We called attention recently to the skill which the nostrum vender
displays in avoiding the particular thorn that pricks him, and his
development of the art of impressively saying, “Nothing in General,” as
exemplified in the advertisements of Fellows’ Syrup. Nostrum sellers
are more canny than original; and when once an idea finds lodgment with
one of them, it is made to serve many masters. Formerly exploiters of
either vicious or worthless nostrums were wont to boast that their
preparations were exploited in a “strictly ethical manner.” Recent
perusal of as choice a lot of advertisements as can be found in the
most degraded of medical journals failed to disclose this claim in a
single instance, although the claim that a preparation is “advertised
only to physicians” is still common.
The advertisement of “Neurosine,” which we reproduce, was the first
one which came to our attention when we searched through some medical
journals for one that would illustrate a discussion of the “original
package” evil. This is the only reason for selecting Neurosine rather
than another. Such half page advertisements and others of similar
size in various medical journals cost a good deal of money and they
presuppose that the Dios Chemical Company is interested in having
original bottles of Neurosine dispensed every time that nostrum is
prescribed.
Why should the firm have any such deep interest in seeing that an
original _bottle_ gets to the patient? Why should it be necessary
to do anything more than see that the genuine _mixture_ reaches the
patient? Does it seem within the bounds of reason that substitution
is so commonly practiced by pharmacists that this firm must go to
large expense to prevent the substitution of spurious mixtures for its
product? Is dishonesty the rule among pharmacists? Common sense rejects
the plea as placing too great a strain on one’s credulity. Obviously,
then, the advertisement does not tell the whole truth, though it does
indeed tell exactly what the nostrum maker wishes to have done, that
is, to have only _original bottles_ dispensed when physicians prescribe
that nostrum. The fact we have; the reason is not far to seek.
[Illustration]
When the pharmacist puts up an ordinary, nonproprietary prescription,
the patient gets no clue from the package as to the nature of the
prescription employed. But when an original bottle of Neurosine is
dispensed, even though the pharmacist puts his own prescription label
on it, the patient sees the difference at once and knows just why
the usual prescription bottle was not employed. He also knows that
he can get the medicine with its original wrapper or label by merely
showing the bottle to the druggist, for the words “Neurosine” and “Dios
Chemical Co.” are blown in the glass. Here, then, may be a plausible
reason for desiring that only original bottles be dispensed.
You may ask, “What difference does it make if the patient does learn
the name of the nostrum, he must go to his physician for advice
concerning its use?” Having learned the name of the remedy that has
been prescribed for sleeplessness, let us say, he proceeds to use
it whenever he imagines that he needs it; and that need, real or
imaginary, has a way of increasing in frequency. As a result, the
patient takes far more Neurosine than the physician would think of
permitting if the matter had not passed entirely beyond his control.
Not only has the patient acquired a dangerous habit of
self-prescribing, but he takes especial delight in recommending his
favorite remedy to friends whose symptoms, real and imaginary, seem to
resemble his own. This offers him an opportunity to prescribe with an
air of authority. It was prescribed for him by Dr. Blank, and it gave
relief, _ergo_ it may be depended on to give relief to others! Thus is
the basis laid for its general use by the laity, when this process is
multiplied sufficiently. The statement is susceptible of easy proof
by any one who cares to investigate the matter for himself. There is
probably no physician worthy of the name who will attempt to deny
that the promiscuous use of hypnotics and narcotics is dangerous, and
certainly no careful physician will deliberately place a narcotic in
the hands of patients to be used freely and without control.
Since we have selected Neurosine at random, so far as this particular
discussion is concerned, it is worth while to inquire into its
composition, the claims that have been made for it and the evidence, if
any exists, for or against its therapeutic value. Even the most active
of hypnotics are worse than useless if they are inferior to other
readily available hypnotics, or if they have undesired side-actions
that outweigh any advantages that they might otherwise have.
The Council on Pharmacy and Chemistry investigated the literature
relating to Neurosine and published its report in The Journal, Jan. 9,
1915, p. 165. According to this report the manufacturers of Neurosine
claimed that each fluidounce contained:
Bromid of potassium, C. P. 40 grains
Bromid of sodium, C. P. 40 grains
Bromid of ammonium, C. P. 40 grains
Bromid of zinc 1 grain
Extract lupulin 32 grains
Cascara sagrada, fl. ex. 40 minims
Extract henbane 0.075 grain
Extract belladonna 0.075 grain
Extract cannabis indica 0.60 grain
Oil bitter almonds 0.60 grain
Aromatic elixir
This chemical blunderbuss was recommended for use in insomnia,
hysteria, neurasthenia, migraine, neuralgia, delirium tremens, epilepsy
and many other conditions. Also it was called an ideal calmative for
children suffering from chorea, the exploiters claiming that “All
authorities recommend the bromids, hyoscyamus and cannabis indica in
this disease.” Oliver T. Osborne, professor of therapeutics in Yale
Medical School, does not mention one of these three drugs in his
discussion of the Medicinal Treatment of Chorea, in the Handbook of
Therapy, though he quotes several authorities in this article. Indeed,
he does not mention one of the ten drugs included in the above formula
of Neurosine in connection with the treatment of this disease. It is a
curious fact that Osborne gives the greatest prominence to the use of
that drug which is claimed to be wanting in the formula of Neurosine,
namely, hydrated chloral.
Perhaps you may have seen temporary relief follow the administration
of Neurosine in chorea, and may argue that theorizing is of little
value in the face of personal experience. We shall not deny that some
may have had that experience, for Osborne calls attention to the fact
that the success of any medicinal treatment must be judged in the
light of the fact that chorea is self-limited, and the intensity of
the symptoms will abate in from two to four weeks. In view of this, we
would hardly dispute the claim that one may administer narcotics, such
as those contained in Neurosine, and the symptoms of chorea may abate
in spite of such mistreatment. In all the years that Neurosine has been
exploited to physicians with such remarkable claims, we have never seen
a report of a careful clinical study in which the product has been used
under the conditions which scientific investigation demands. Would you
prescribe any nonproprietary preparations which had never been studied
clinically, if a horse-shoer or grocer’s boy told you it would cure
epilepsy or malaria?
According to an editorial note appended to the report of the Council
on Neurosine, the Dios Chemical Company consisted at that time (1915)
of J. H. Chambers, his wife and two sons. It appeared that Chambers
never claimed to have any special knowledge of chemistry, pharmacy or
medicine, yet we find that he arrogated to himself or to his employees
the right to offer therapeutic advice to the medical profession, and
even to direct them as to how they should prescribe a given mixture.
We sometimes fail to see the forest because of the trees. It may help
us to obtain a better perspective, in a problem that concerns us
intimately, by resorting to a hypothetic case, if a close analogy is
maintained. In order that we may see ourselves as others see us in
such a situation, let us consider the following imaginary case: You
become involved in a lawsuit in which an effort is made to deprive you
of your property and your liberty. You seek what you had reason to
believe was competent legal advice; but, nevertheless, you lose your
case and find yourself deprived of your property and your liberty. Now
let us suppose further that you discover, when too late to permit you
to correct your mistake, that your legal adviser (we can hardly call
such a man a lawyer) had been acting all along under the guidance of a
plumber who made no pretense of knowing anything about law. How would
you feel regarding that pretended lawyer? Would you feel that you had
been treated fairly? Would you feel disposed to speak with all charity
of him, to recommend him to those in need of legal advice?
You would probably feel toward such a lawyer as patients must feel
toward physicians who prescribe proprietary nostrums based on
information and advice offered by those who, though without any special
knowledge of chemistry, pharmacy or medicine, will be benefited
financially if their information and advice are accepted and acted
on.--(_From The Journal A. M. A., April 27, 1918._)
ANASARCIN ADVERTISING[I]
[I] See index for other articles on Anasarcin.
_To the Editor_:--As an old Fellow of the A. M. A. I beg to present
the following facts to you, and to ask if anything can be done by you
to expose the methods of these people: A concern calling itself “The
Anasarcin Chem. Co.” of Winchester, Tenn., has caused to be sent to
physicians a chart on the subject of “Diagnostics of Renal Diseases.”
This chart contains eighteen plates, which were all taken without
knowledge or permission of either myself or my publishers, William
Wood & Co., from the third edition of my book on “Urinary Analysis
and Diagnosis.” The plates are partly composite plates, but mostly
portions of plates, exactly reproduced from my book. I at once caused
my publishers to write to the Anasarcin Company; and a few days ago I
received a letter from a Dr. H. Elliott Bates of 118 East Twenty-Eighth
Street, New York, whose letterhead says, “Medical Advertising.” In this
letter the writer says that it was he who suggested the sending of such
a chart, and admits that all the plates were taken from my book. In
this letter he offers to have a letter sent to every physician of the
country “in which it is explicitly stated that the cuts on the chart
were taken from your book, and that complete information regarding
the matters treated on the chart can be found in your book.” In other
words he offers to advertise my book free of cost to me, so that I
should take no further steps in the matter. I consider this entire
matter an outrage, and thought it best to write to you for advice,
since my publishers seem to think that in spite of the violation of the
copyright nothing can be done.
Besides the cuts, some of the text on the chart is bodily taken from
my book, while some of the other text, not taken from my book, but
apparently compiled from different articles, is in part entirely wrong,
so much so that I must be ashamed of its being associated with any of
my own work.
By giving this letter your early consideration, and advising me what
you think it best for me to do, you would greatly oblige
Louis Heitzman, M.D., New York.
[Comment.--Readers of The Journal are, of course, familiar with the
articles[246] that have been published on “Anasarcin,” the “dropsy
cure”! Knowing the standard of ethics that the Anasarcin concern adopts
in the exploitation of its ridiculous squill mixture, our readers
will not be surprised at the standard of commercial ethics which
would justify the appropriation of copyrighted scientific material
for nostrum advertising purposes. The statement of Dr. Heitzmann’s
publishers that “in spite of a violation of copyright nothing can be
done” is, of course, incorrect. Something _can_ be done by those who
hold the copyright.--Ed.]--(_From The Journal A. M. A., Oct. 18, 1919._)
[246] J. A. M. A. =46=:288 (Jan. 27) 1906; ibid. =48=:1535 (May 4) 1907;
ibid. =48=:1614 (May 11) 1907, and ibid. =49=:1992 (Dec. 8) 1917.
ANTIMERISTEM-SCHMIDT
Some, possibly many, of our readers have received a letter from
Cologne, Germany, from the “Bakteriologisch-Chemisches Laboratorium
Wolfgang Schmidt.” The letter contains a circular directing the
attention of American physicians to “Antimeristem-Schmidt.” It also
contains some advertising leaflets. One physician in sending this
material to The Journal writes:
“A copy of the enclosed circulars has been sent to many of the
physicians in this city, and probably elsewhere. Perhaps it has
already been called to your attention. Let us be as liberal as
possible with our recent enemies. The sooner the old channels of
scientific communication are re-opened, the better. But let us
not allow such blatant commercialism from a foreign country to go
unprotested, any more than we should if it were from our own.”
It should be noted in passing that the envelop in which the Wolfgang
Schmidt letter came has on its face a rubber-stamped impress to the
effect: “Concerns Cancer Treatment.” The circular letter declares that
by means of Antimeristem-Schmidt “either a cure or improvement has been
effected in numerous inoperable cases” of malignant tumors. American
physicians are asked “to employ the preparation when occasion arises”
and are assured that “every medical man in city or country will be
able to carry out treatment without preliminary knowledge.” With the
letter are two leaflets discussing the use and administration of the
product; one contained what was called a “Synopsis of some of the more
recent publications regarding the employment of Antimeristem-Schmidt in
inoperable malignant tumors.” The “recent” publications comprised three
articles published in 1910 and one published in 1912!
Antimeristem-Schmidt was rather widely exploited some six or seven
years ago. As was explained in The Journal, March 8, 1913, p. 766, it
is a preparation claimed to be useful in the treatment of inoperable
cancer and as a supplementary treatment after operations for cancer.
The treatment is founded on a theory advanced by one O. Schmidt that
the cause of cancer is found in a fungus, _Mucor racemosus_, which,
Schmidt at first asserted, carried a protozoon which he regarded as
the real cause of the disease. The vaccine is said to be prepared from
cultures from this fungus. While Schmidt claims that he has been able
to produce cancer by means of the organism, scientific research has not
verified his claims. Extensive clinical trials have shown the treatment
to be without effect. The Journal also advised its readers on April 19,
1913, that no license for the sale of Antimeristem-Schmidt had been
granted by the Treasury Department and, therefore, its importation into
this country was prohibited. Neither the therapeutic nor the legal
status of the product has been changed since then.--(_From The Journal
A.M.A., Dec. 6, 1919._)
ANTIPHLOGISTINE
_To the Editor_:--Last September, my chief, Dr. J. S. Millard,
received a letter from the Denver Chemical Mfg. Co., manufacturers of
“Antiphlogistine.” This letter purported to quote many large commercial
concerns as testifying to the value of Antiphlogistine. Recently, I
doubted the veracity of these claims and wrote to some of those quoted.
I quote from the original letter of the Antiphlogistine company:
“The surgeon to the electric light and electric railroad company in
New Orleans says that Antiphlogistine is the finest thing he has
ever used in burns, especially flash and brush burns.
“The physician to the New York Edison Co. makes a similar
statement. He says that the application gives speedy relief and the
burns heal quickly without scars.”
I wrote to Dr. John Woodman, the physician to the New York Edison Co.,
who replied in part as follows:
“The Denver Chemical Manufacturing Company have no authority to
quote me.... I gave Antiphlogistine a thorough trial, and found it
had a very limited use, and I cannot recommend it for burns....”
Again, the Antiphlogistine letter said:
“It may be of interest to you to know that at the emergency
hospital of the Ford Automobile Co. in Detroit, Antiphlogistine is
carried in stock and is used extensively by the three physicians
in burns, bruises, infected wounds, sprains and other traumatic
conditions which are constantly arising in such a plant....”
I wrote to Dr. Mead who replied as follows:
“In answer to your letter of January 25th, will state that no
Antiphlogistine has been purchased or used in this hospital for
years past, and I cannot imagine why the representative of the
Denver Chemical Company should make such a statement as attributed
to him....”
He adds that “Antiphlogistine has never been used” in his department
“on an open wound, abrasion or burn.” Is there not some way that such
exploitation of our large companies can be prevented?
A. G. Gould, M.D., Akron, Ohio.
Plant Physician, the Goodyear Tire & Rubber Co.-(_From the Journal
A.M.A., Feb. 23, 1918._)
“AUTO-HEMIC SERUM”
A Cure for Laziness, Ugliness, Frigidity and Many Other Things
The following letters are typical of many that have been received
asking for information regarding Dr. L. D. Rogers and his “Auto-Hemic
Serum.” This from a physician in New York state:
“Can you give me any information in reference to Dr. Rogers of
Chicago, Ill., who has an Auto-Hemic Institute?”
And this from Kansas:
“Just received a letter from a Dr. L. D. Rogers, 2812 North Clark
St., who is anxious to sell me a course in ‘Auto-Hemic Therapy.’
Would you kindly inform me what he has to sell? He did not tell me
what it consisted of; am inclined to believe it is a rank fake.
Kindly let me know what _The Journal_ thinks about it. Just what is
it? In the letter they claim that it is practically a panacea for
every blood disease.”
This from Maine:
“What is Auto-Hemic Therapy? I have a handsome red and yellow
circular from the Ideal Life Extension Press, 2812 North Clark St.,
Chicago, soliciting subscriptions to their publication, offering
as a bonus this book, ‘Auto-Hemic Therapy’ by L. D. Rogers, A.M.,
M.D., LL.D., Chicago, and membership in the American Medical Union.”
THE NATIONAL MEDICAL UNIVERSITY
In order better to appreciate the probable scientific status of
“Auto-Hemic Serum,” it is well briefly to sketch some of the previous
activities of its discoverer, Dr. L. D. Rogers. For many years Rogers
was the head and chief owner of the National Medical University of
Chicago, a low-grade school of the “sun-down” variety. The “university”
is now out of existence and for some time before it went out of
existence was not recognized either by the board of health of the state
in which it operated or by the boards of the majority of the other
states in the Union. The report of the Carnegie Foundation on medical
education had this to say about the laboratory facilities of Rogers’
school:
“The school occupies a badly lighted building, containing nothing
that can be dignified by the name of equipment. There has been
no dissecting thus far (October to the middle of April, 1909),
anatomy being didactically taught. Persistent inquiry for the
‘dissecting-room’ was, however, finally rewarded by the sight of
a dirty, unused, and almost inaccessible room containing a putrid
corpse, several of the members of which had been hacked off. There
is a large room called the chemical laboratory, its equipment
‘locked up,’ the tables spotless. ‘About ten’ oil-immersion
microscopes are claimed--also ‘locked up in the storeroom.’ There
is not even a pretense of anything else. Classes in session were
all taking dictation.”
Dr. Rogers is, or was, if he is not still, “Permanent Secretary” of
the “National Association of Panpathic Physicians”--whatever that is.
In fact, one of Dr. Rogers’ specialties seems to be the founding of
quasimedical organizations--organizations, apparently, which may prove
useful in the promulgation of such projects as he may, at the time,
be interested in. A few years ago, Rogers was exploiting a “cancer
serum” and, _presto_, the “American Cancer Research Society” came into
being, L. D. Rogers, president. Soon thereafter certain members of the
profession were circularized urging them to purchase shares in the
“Cancer Research Laboratory and Hospital,” par value $10. Apparently,
the profession did not invest.
A few years ago, also, L. D. Rogers’ name appeared on the “Faculty”
list of the “American Post-Graduate School,” a concern which
granted--on the mail-order plan--a long line of sonorous degrees and an
equally complete line of ornate diplomas.
THE JAPANESE CONSUMPTION CURE
Then, in 1915, there appeared in the classified columns of certain
newspapers the following advertisement:
TUBERCULOSIS--New Japanese treatment;
to prove merits and give discovery quick
publicity will send 10 days’ treatment free.
DR. ROGERS, 546 Surf St., Chicago.
So far as we have been able to learn, Rogers, for some unexplained
reason, did not call into existence out of the vastly deep a
“Japanese-American Tuberculosis Research Society.” This consumption
cure apparently died of inanition.
Then came the “Auto-Hemic Serum” with its inevitable sequel, the
“National Society of Auto-Hemic Practitioners.” Another adjunct to the
serum exploitation is the _North American Journal of Homeopathy_, the
official organ of the “Auto-Hemic Practitioners” and of the “American
Medical Union” and possibly of some other “societies”--but not
representative of homeopathy!
WHAT IS AUTO-HEMIC THERAPY
What is this new therapy? According to a very lurid poster, it is
described as “The Missing Link in Medicine”--possibly referring to
the ease with which one may make monkeys of certain physicians. More
specifically, although still vaguely, we learn:
“It consists in giving the patient a solution made by attenuating,
hemolizing, incubating and potenizing a few drops of his or her
own blood, and administering it according to a refined technic
developed by the author.”
Elsewhere it is said to consist:
“... in taking five drops (or some multiple of five) of blood from
a vein and putting it into nineteen times as much sterilized,
distilled water, and incubating it at fever temperature for
twenty-four hours, and then making further dilutions according to
the needs of the case, as can be determined only by a physician
skilled in its use.”
Neither of these statements, of course, describes the “refined technic”
of those “skilled in its use,” but those who are interested can, by
sending Dr. L. D. Rogers, “One Hundred Dollars cash-in-advance” get a
mail-order course in this new marvel.
But if it is rather expensive to learn just how to use “Auto-Hemic
Serum,” it does not cost so much to learn what the “serum” will do.
Rogers has written a book on the subject, “Auto-Hemic Therapy,” which
is used as a premium for subscriptions to the _North American Journal
of Homeopathy_, price $5.00 per year, payable in advance. In the book
Dr. Rogers modestly assures his readers that he considers his discovery
more important than that of Alexis Carrel, winner of a Nobel Prize.
A CURE FOR LAZINESS
One of the chief virtues claimed for this serum is that of developing
in the patient who takes it an unbounded energy that, apparently,
makes him want to work himself to death. In some sensational articles
that have appeared in Sunday editions of newspapers on Rogers’ serum,
the stuff has been described as “Lazy Serum.” One of the first
cases described in the Rogers book is that of a young waiter, “a
good-for-nothing lazy fellow who would not work and would not pay for
medical services” and who was turned over to Dr. Rogers’ free clinic.
He was given the serum on Thursday and was told to report Saturday. He
did not return until Monday, his excuse being that “he worked all day
Saturday until midnight and all day Sunday and felt as if he could work
all day and all night without rest.” The “case report” ends:
“... finally remarking, ‘I feel like a bird’ he flew out of the
classroom and we never saw him again.”
HOUSEWIVES TAKE NOTICE
The next case described is that of a servant girl who had not worked
for a year; within a week after taking the “Auto-Hemic Serum,” “she
voluntarily beat carpets till she blistered her hands.” Then there
was the rooming house keeper who had spent more than half of each day
in bed. After an “Auto-Hemic” injection she “discharged her maid and
janitor ... and did all the work of her twelve room house herself,
beating rugs, firing furnace and carrying out ashes besides doing some
of the laundry.” “Case No. 7176” is interesting: A man, generally
considered the laziest person in his community and with a habit of
“drinking thirty whiskies a day,” took “Auto-Hemic Serum.” He stopped
drinking, shaved himself and changed from “a “bum” to that of a sober,
clean, wholesome, bright and honest workman.” Then there was the case
of the “lady physician” who “took the serum one evening and the next
morning reported that she had the ‘giggles’ all day”; also she became
“more magnetic.” More remarkable still was the case of the young woman
clerk in a retail store who, after taking the serum, “astonished her
employer by volunteering to work overtime.” In the chapter dealing
with “Ills Peculiar to Women” Dr. Rogers details the moving story of
a _man_ to whom the “serum” was given and who reported that “about
the third twenty-four hours after taking it his bowels moved forty
times”--nevertheless, “he felt no exhaustion.”
In all phases of human activity the serum seems to work wonders. “The
cases are numerous in which the frigidity of both sexes have [_sic_]
melted after Auto-Hemic treatment.” A young married woman with a morbid
dislike for her husband took the serum and within a week “became
normal.” The discoverer suggests that in some cases there is no doubt
that this serum “would prevent divorce.” A 40 year old woman who could
not endure to wear any waists but white or black was able, it seems,
after taking the serum to tolerate a veritable Jacob’s coat.
Is, then, “Auto-Hemic Serum” good for everything? Let Dr. Rogers answer:
“Briefly stated, without any great exaggeration, this new modified
serum treatment is good for anything that is the matter with you,
provided the cause is not organic, mechanical or bacterial.”
One infers that in the inorganic, mental, spiritual and nonbacterial
spheres the stuff is supreme. But it has its limitations. For instance,
Dr. Rogers states that he once had “a very troublesome cough which
lasted several weeks, but did not yield to this serum.” Reaching the
conclusion that some other treatment was necessary “he had the bones of
his neck ‘adjusted’ and got immediate relief.”
AS A COMPLEXION BEAUTIFIER
The serum “cannot be made up by the barrel and sold at wholesale or
retail”:
“If it could be bottled and stored and sold at retail like a patent
medicine, the demand for it as a complexion beautifier alone would
net the proprietor millions. More than one person a few days after
taking the treatment has been wrongly accused of painting.”
Should any of The Journal readers decide to take the $100 mail-order
course in “Auto-Hemic Therapy” he should realize that even after he
has done so there are certain restrictions in the practice of this
“therapy.” In no case must he administer “a course of Auto-Hemic
Treatment” for “less than $100, paid in advance.” The only exceptions
to this rule are “cases of absolute charity, expectant mothers and to
persons positively unable to pay that amount.” Furthermore, Dr. Rogers
says that for the reputation of his method, as well as for the good of
all concerned, “I insist that the entire fee be paid in advance and
that the course extend over a period of one year whether the patient
needs few or many treatments.”
DOLLARS AND CENTS
For those who do not wish to take the mail-order course, Rogers offers
to prepare individual specimens of the “serum” from blood that is
sent to him by the physician. The cost of this “serum” is $5.00, “in
advance,” of course.
Still emphasizing the commercial side, “Auto-Hemic Therapy” is
especially recommended to “the general practitioner growing old and
the physician who is ambitious to build up a creditable and lucrative
practice” because “the health of four people out of five (old or young,
whether they consider themselves sick or well) taken at random can
be improved by this method of treatment”! An Ohio physician was said
to have doubled his $3,000 practice in two years after starting the
“Auto-Hemic” method. A Virginia physician is alleged to have “increased
his income $10,000 a year.” A Pennsylvania physician urged by Rogers
to send $150.00 for the mail-order course, was assured that this “is
merely a nominal amount, as most of the doctors have been able to get
this amount back the first month.”
But enough. The story, were it not for the tragic element that forms
the background, would be amusing. But it _is_ tragic!--(_From The
Journal A.M.A., Feb. 14, 1920._)
“AUTOLYSIN” ADVERTISING
_To the Editor_:--Enclosed is a little booklet I received today from
the Goodhue Publishing Co., of New York, exploiting the Horowitz-Beebe
cure-all for cancer, which, were it not for certain obvious serious
features, would make humorous reading.
What psychologic explanation can be made of the fact that there are
always sufficient numbers of suckers to make such pseudoscientific
adventures profitable?
H. C. Dodge, M.D., steamboat Springs, Colo.
_To the Editor_:--In my professional life I have been flooded with
the usual number of insults to intelligence both by mail and by the
softspoken detail man. As a result, I have no doubt, of the active
propaganda for reform carried on by The Journal, these insults have
lost a certain quality of “rawness” and become much more cleverly done.
One of these has just been perpetrated on the profession which will
probably hold the championship pennant for 1916, although I admit that
it is early in the year to begin prophecy. A very modestly bound, well
printed volume comes to my desk with the compliments of the publishers.
At the end of the volume is a group of highly ethical advertisements
of other books of the author. So far, so good. The last four pages,
however, contain the advertisement of a forthcoming book on the
“autolysin” treatment of inoperable cancer. Perhaps we might forgive
this were it not for the following paragraph: “This book tells how
the general practitioner ... may take an active hand in fighting the
malady. The weapons he requires are an ordinary hypodermic syringe and
some ampules of Autolysin. The syringe he already possesses. Autolysin
he may secure, if he is a legally qualified practitioner, by writing,”
etc. Incidentally, the book is advertised to the Intelligent Layman.
Isn’t it beautiful? Too bad the lamented F. F. F. with his mock turtles
or those prominent eugenists of scopolamin-morphin fame could not take
a lesson in advertising. It was not very long ago that we were invited
to come East and learn how to use “autolysin,” or else pay the rather
heavy fee for an imported tutor. Now all we need is a “gun” and some of
the “dope.” All this is interesting in view of the recent article on
the failure of “autolysin” in mouse tumor. It is a foregone conclusion
that a lot of “autolysin” will be used, so cancer patients, who have
been told that they have cancer, will get better through suggestion,
and a lot of enthusiastic reports will pour in from medical brethren
who have never studied psychology. Then the thing will slump and we
shall all be ready for the next fad.
Nevertheless, each one of these things furnishes us with a text for
another sermon on ethics of medical advertising, so I suppose they do
not live in vain.
J. W. Force, M.D., Berkeley, Calif.
Assistant Professor of Epidemiology, University of California.
[Comment.--With each of the foregoing communications is a circular
letter from the Goodhue Company, advertising Dr. Henry Smith Williams’
book on “The Autolysin Treatment of Cancer.” With this circular is a
booklet entitled “Notes on the Treatment of Inoperable Cancer with
the New Remedy AUTOLYSIN (Horowitz-Beebe) Issued by the Autolysin
Laboratory.” Similar circular letters and pamphlets have been sent to
The Journal from various parts of the country. The Goodhue Company,
publishers, therefore are apparently killing two birds with one
stone--advertising the book as well as “Autolysin.”
The Journal has been informed that Henry Smith Williams in some of his
magazine articles uses the pen name “Stoddard Goodhue,” and that Henry
Smith Williams is a part owner of the Goodhue Publishing Company.
Articles on “Autolysin” will be found in The Journal, Nov. 6, 1915, pp.
1641, 1647 and 1662. The article on “Action of ‘Autolysin’ on Mouse
Tumors,” by Dr. Francis Carter Wood, appeared in The Journal, Jan. 8,
1916, p. 94.-- Ed.]--(_Correspondence in The Journal A.M.A., Jan. 29,
1916._)
“BASIC CANCER RESEARCH” AND “COSMOPOLITAN
CANCER RESEARCH SOCIETY”
Medical journals, and some other technical publications, have
received recently what purport to be items of news value sent out by
the “Medical News Bureau,” 77 Seventh Ave., Brooklyn, New York. The
“manager” of this alleged bureau is given as D. E. Woolley. These “news
items” are undated but are marked: “(For immediate release)” One of
these starts with the statement, attributed to Mme. Curie, that cancer
can be cured by radium and then continues:
“Cancer can be cured by the use of selenium and tellurium, more
plentiful and less costly elements,” says F. W. Humphreys of
Brooklyn, an American born student of chemistry and science who has
devoted years to the study of the cause of cancer and the discovery
of methods for relief....
“For the purpose of further developing methods of control and
treatment of disease by the use of selenium and tellurium
discovered by a number of local scientists, chemists and
physicians, the Basic Cancer Research has been organized and an
efficient laboratory established at 847 Union Street, Brooklyn....”
“Through the education of the people and special instruction to
physicians it is hoped it may soon be possible to gain control of
and eradicate the disease which now appears so great a menace.
Mr. F. W. Humphrey, one of the organizers of the new institution,
estimates that within ten years, or perhaps less time, cancer will
no longer be considered a fatal disease.”
Evidently the joker here is the “Basic Cancer Research” of 847 Union
Street, Brooklyn!
Newspapers are approached from a different angle. They receive free
publicity matter on stationery reading “Cosmopolitan Cancer Research
Society” (D. E. Woolley, secretary), 847 Union St., Brooklyn, N. Y.
With this matter is a letter from Woolley addressed to the editor of
the paper to which the stuff is sent and asking:
“In the interest of suffering humanity will you please give space
to the enclosed?
“No object of greater importance has ever been presented for your
helpful consideration. Thousands are dying whom you can help save.”
According to the “news item” that accompanies this letter the
“Cosmopolitan Cancer Research Society” has been founded for the purpose
of “investigating and developing methods” by which cancer “may be
successfully combated and eventually eradicated.” It states further
that the “society” will “disseminate information concerning symptoms,
diagnosis, treatment and methods of prevention” of cancer. Furthermore,
the membership of the society “includes physicians, scientists and
chemists of prominence, laymen of means, and the sympathetically
inclined from all walks of life.” Nor is this all!
“Doctor Frederick Klein the eminent authority on urinology and the
chemistry of cancer, has evolved a new colorimetric test which is
a most wonderful and valuable discovery in the diagnosis of cancer
and various other diseases. This test will be particularly valuable
in all life extension work because it determines, even in children
the possibility of predisposition toward any particular disease,
whether tuberculosis, cancer, diabetes or any of the diseases which
in later life may become fatal. It determines also the vitality
of the subject enabling the physician to accurately determine the
condition of any of the vital organs.”
We learn in closing that memberships in the “society” are “graduated
from $1.00 upwards according to the ability and disposition of those
who may be interested.”
Located at 77 Seventh Avenue, from which the press agent material of
the “Medical News Bureau” is sent, is the “Basic Chemical Corporation
of America.” According to such information as we have been able to
get, the president of this concern is F. W. Humphreys, the “student of
chemistry and science who has devoted years to the study of the cause
of cancer and the discovery of methods of relief.” We are informed that
Mr. Humphreys was for a while in the employ of a “chemical company” of
Philadelphia, and has been in the photographic line down in Virginia
and later was connected with a real estate concern in Brooklyn. Another
officer of the Basic Chemical Corporation is said to have been in the
grocery line in a small village in Missouri, selling out and later
coming to Brooklyn and entering the insurance business. Still another
officer, it seems, was in the fish business. In addition to these three
officers, there are two directors, one of whom is in the fancy grocery
line, and the other is a local practicing physician whose name we find
in the Propaganda department’s testimonial file under Sanmetto and
Arsenauro.
The Dr. Frederick Klein, who is described as the “eminent authority on
urinology and the chemistry of cancer,” is not a physician but claims
a Ph.D. from Munich, Bavaria. Klein claims to have developed certain
urinary tests. One of these, according to him, “indicates the body
_Vitality_ with great accuracy,” another proves the presence of cancer,
a third is the “syphilis test” and a fourth is the “pregnancy test.”
And these are not all!
Those who read the reports of the Council on Pharmacy and Chemistry may
remember that Frederick Klein is the gentleman who made “Sulfo-Selene,”
which the Council, in refusing it recognition, described as a “mixture
containing a selenium compound of undetermined composition produced
by reduction of nitro-selenous acid with sulphurous acid, mixed with
bile salts and diluents.” Sulfo-Selene was widely exploited in the
newspapers in 1916 as a remedy for cancer, and Klein got a good deal of
publicity at that time.
Just what product the Basic Chemical Corporation of America is
putting, or is about to put, on the market we do not know. From the
rather vague talk about selenium and Frederick Klein’s marvelous
diagnostic discoveries, it might be inferred that “Sulfo-Selene” was
to be resurrected. Be that as it may, it seems fairly obvious that the
material being sent out by D. E. Woolley--whether as “Manager” of the
“Medical News Bureau” or as “Secretary” of the “Cosmopolitan Cancer
Research Society”--is advertising matter in the guise of news.
In this connection it is worth noting that the American Newspaper
Publishers’ Association, in a special bulletin issued in 1909,
published a very complete list of press agents and the interests these
agents represented. This list contains the name D. E. Woolley, who then
was sending out press notices for the National Association of Piano
Dealers of America. Is this the gentleman who is now acting as press
agent for the Basic Chemical Corporation of America? If it is, it may
be that the slump in the piano trade has caused Mr. Woolley to turn
from musical instruments to cancer cures.--(_From The Journal A. M. A.,
Sept. 3, 1921._)
Seleni-Bascca
In the issue of September 3 The Journal called attention to a campaign
of free publicity that was being instituted by a Brooklyn concern that,
apparently, had for sale an alleged remedy for cancer. The press agent
material was of two kinds--for medical journals and for newspapers.
That which went to the medical journals was sent out on the stationery
of the “Medical News Bureau,” 77 Seventh Ave., Brooklyn. The “manager”
of the bureau was given as D. E. Woolley. The items sent out to medical
journals stated that the “Basic Cancer Research” had been organized to
develop a treatment of cancer by the use of selenium and tellurium.
The material received by newspapers was sent out by the “Cosmopolitan
Cancer Research Society,” 847 Union St., Brooklyn (the same address
as the “Basic Cancer Research”). The “Secretary” of the “Cosmopolitan
Cancer Research” was D. E. Woolley!
The name of one “Dr. Frederick Klein” loomed large in the matter sent
out by the “Cosmopolitan Cancer Research Society.” Klein, we were told,
is “the eminent authority on urinology and the chemistry of cancer.”
The Journal called attention to the fact that Frederick Klein’s name
was not unknown in the Propaganda files, as he was the gentleman who
manufactured “Sulfo-Selene,” a product that was widely heralded in the
newspapers in 1916 as a remedy for cancer. It was also brought out
that Klein, who is not a physician, claims to have evolved certain
remarkable urinary diagnostic tests whereby the presence of cancer,
syphilis, etc., may be determined.
More than a month after the publication of The Journal’s article,
a letter was received (October 8) from Frederick Klein. To quote
literally from part of the letter:
“In the above _Journal_ dated Sept. 3th, Vol. 77, on page 805,
regarding the ‘Cosmopolitan Cancer Research Society’ you have
amongst others, mentioned my name Dr. Frederick Klein.
“I wish to inform you that I have given my legal adviser the order
to write a note to the above Cosmopolitan Cancer Research Society,
847 Union St., Brooklyn, forbidden them to the effect that my name
_should not_ be used by above society in any form or writing in any
of their transactions, this has been done some time ago to prevent
unethical conceptions concerning myself.”
Shortly after the article of September 3 another item appeared in
the newspapers throughout the country to the effect that the Cancer
Research Society was offering a “$100,000 Cancer Prize” for a
“medicinal cure for cancer.” Many of the newspapers of the country
seemed to bite on this piece of free publicity. This was in the first
week of October. In the third week of the same month a Brooklyn paper
announced that 3,000 people had submitted formulas for curing cancer
to the Cosmopolitan Cancer Research Society. The article containing
this announcement gave interesting descriptions of some of the “cures”
submitted and closed with the statement that the Cosmopolitan Cancer
Research Society was establishing “clinics” in various cities. It ended
with the statement:
“All treatments are confidential. In this respect the society had
the cooperation of the Brooklyn Bureau of Charities. It also has
the cooperation of the American Medical Association.”
The closing sentence is, of course, unequivocally false.
At the time of The Journal’s article the name of the particular
preparation which the Basic Chemical Corporation of America was putting
out was unknown. Shortly after the article appeared it was learned
that the product was on the market as “Seleni-Bascca.” A physician,
himself a sufferer from carcinoma, after reading the article of
September 3, sent The Journal some correspondence he had received
from the Cosmopolitan Cancer Research Society regarding the alleged
cure. One piece was a letter signed “F. W. Humphrey, Acting Director;
Dictated by Dr. George D. Barney,” which read in part:
“Our claim is a very simple one indeed, namely that the use of
a proper preparation of Selenium (Seleni-Bascca) restores the
Sulphur metabolism to normal; we claim that cancer cannot exist in
any form, when the Sulphur metabolism is normal, the results from
the proper use of Seleni-Bascca in cases of Carcinoma are quick
and lasting, the Medical Profession can hardly realize that in
this modest treatment a remedy for the Dreaded Carcinoma has been
discovered.
“Seleni-Bascca in its colloidal form is quickly taken up by the
blood stream, reaches the finest tissues and almost immediately
resists the further growth of the disease. The research work has
been going on since 1901, under the direction of Dr. Frederick
Klein, in connection with Medical Men who have proved to their own
satisfaction that Seleni-Bascca should be used as a treatment in
every case of malignancy.”
Seleni-Bascca comes in small vials containing fifty tablets. Each vial
bears a label reading:
“_SELENIBASCCA._ A mixture of Colloidal Selenium in tablet form.
Recommended in the internal treatment of Carcinoma and some other
cases of faulty metabolism.”
Some of the preparation was turned over to the A. M. A. Chemical
Laboratory with the request that the tablets be examined to determine
whether or not they contained, as claimed, selenium in colloidal form.
The laboratory report follows:
CHEMICAL REPORT
“An original vial of ‘Seleni-Bascca’ (Basic Chemical Corporation of
America) was examined in the A. M. A. Chemical Laboratory to determine
whether or not the substance contained colloidal selenium. The bottle
contained 50 tablets weighing approximately 0.1 gm. (about 1-1/2 gr.)
each. The major portion of the tablet was soluble in hot water.
Qualitative tests indicated the presence of chlorid, sulphate, small
amount of nitrate, potassium, sodium, starch, talc and selenium.
Tellurium was not found to be present. The ash was equivalent to 5.5
per cent.; over one-half of the ash consisted of a talc-like substance.
The amount of selenium present in the specimen examined was only about
1.3 per cent.
“In the literature sent out by The Basic Chemical Corporation, ‘Dr.
Frederick Klein’ is mentioned as chemist. Several years ago, the
Council on Pharmacy and Chemistry investigated ‘Sulfo-Selene,’ a cancer
remedy, with which the same ‘Dr. Klein’ was connected. The alleged
composition of ‘Sulfo-Selene,’ as given to the Council, was:
“Selenium .25
“Sulphur (partially in colloidal .10
and partially in crystalloid state)
“Potassium carbonate .10
“Nitrogen .05
“Bile Salts .50
“To which is added an inert base or vehicle;
as sugar of milk or amylum.”
“It was claimed that ‘Sulfo-Selene’ was prepared by reducing
nitro-selenious acid with sulphurous acid, neutralizing with potassium
bicarbonate and then adding bile salts. Assuming that the composition
claimed for ‘Sulfo-Selene’ was correct the analysis of ‘Seleni-Bascca’
shows that the two products resemble each other. The tests, however,
failed to reveal in ‘Seleni-Bascca’ the presence of the bile salts
claimed to have been present in ‘Sulfo-Selene.’”
“The product is not colloidal as claimed as the selenium can be removed
by ordinary filtration.”--(_From The Journal A. M. A., Nov. 19, 1921._)
Repudiated by the Brooklyn Bureau of Charities
_To the Editor_:--My attention has been called to the fact that there
appears in a recent issue of The Journal of the American Medical
Association a statement that the Cosmopolitan Cancer Research Society,
located at 847 Union Street, Brooklyn, has the cooperation of the
Brooklyn Bureau of Charities. In reply may I say that the Bureau of
Charities has no connection, understanding, or relationship whatever,
with the Cosmopolitan Cancer Research Society, and has never sent a
patient to them.
T. J. Riley, Brooklyn.
Secretary, Brooklyn Bureau of Charities.--_Correspondence from The
Journal A. M. A., Dec. 24, 1921._
BELL-ANS (PAPAYANS, BELL)[J]
As the New York Tribune’s “Ad-Visor” Sees It
[J] See index for additional article on Bell-Ans.
“Why avoid draughts? Sit by an open window if you want to! Just
take a few drops of Sneeze-o before you go into the draught and
after you come out of it, and you’ll never catch cold.
“Don’t be afraid of contagion. Kiss your Uncle Ebenezer, even if
he’s dying of tuberculosis! Just fortify yourself with a sip of
Lungicide before you go to his bedside, and another when you come
away, and you’ll be taking no risk.
“Are you going to sit there and let the other folks eat up all
the good things just because you are afraid to pitch in, when 2
or 3 Bell-Ans taken before and after the meal would enable you to
enjoy your share of all that’s coming without a bit of discomfort
or distress? Bell-Ans has restored the pleasures of the table to
thousands who say: ‘I can now eat anything and plenty of it, too.’”
“The first two blurbs are The Ad-Visor’s. The third is a bona fide
advertisement of Bell-Ans, aimed to catch the holiday trade. They are
all patterned after the same style and the first two are no more lacking
in logic than the last. Overeat--deliberately court indigestion--invite
gout--don’t be a gourmet, be a gourmand--be an anti-Hoover and eat a lot
of food, whether you need it or not; than take Bell-Ans. If it doesn’t
‘absolutely remove indigestion,’ your druggist will give you back your
money! Could anything be fairer than that?
“Such copy as this is not limited in its evil effects to the misguided
individual who eats lobster and ice cream at midnight and trusts to
Bell-Ans to atone for his indiscretion. The most serious effect of such
reckless advice is the example which the advertising sets to other
advertisers.”
The comments just quoted are from the Ad-Visor department of the New
York _Tribune_ of Feb. 7, 1918. They are respectfully referred to the
_New York Medical Journal_, the _International Journal of Surgery_ and
the _Woman’s Medical Journal_--three presumably scientific publications
that through their advertising pages urge physicians to prescribe
Bell-ans.--(_From The Journal A.M.A., Feb. 23, 1918._)
CAMPHO-PHENIQUE
Appealing to the New Fledged Graduate.
The secretary of the Harvard University Medical School received from
the Campho-Phenique Company of St. Louis a letter that, presumably, has
been sent to most of the medical colleges of the country. It read:
“We wish to supply the senior class of all Medical Colleges with
physicians’ samples of CAMPHO-PHENIQUE Liquid and CAMPHO-PHENIQUE
Powder, and Ointment for 1918.
“We will thank you very kindly if you will send us a communication
stating the number of students in your graduating class, and if
possible, we would like the name of each and every student, that we
may send him personally a sample of CAMPHO-PHENIQUE. In this way,
we are sure the party receives the sample.”
Presumably, the Campho-Phenique concern believes in following the old
advice: Catch ’em young! In this connection, it may be well briefly
to call to the attention of fourth-year medical students the results
of the investigation of the Council on Pharmacy and Chemistry of
Campho-Phenique. The Council’s findings on Campho-Phenique Liquid
were to the effect that the preparation, which was exploited under a
false “formula,” was, essentially, a solution of camphor and phenol in
liquid petrolatum, substances well known in medicine and none of which
under its own name has been credited with possessing any superlative
virtues. The Council’s verdict on Campho-Phenique Powder was that “for
all practical purposes it is essentially a camphorated talcum powder”
containing, apparently, sufficient camphor and phenol to give the
talcum powder an odor. It was further brought out in the Council’s
report that the Campho-Phenique Company was in effect one of the
numerous trade names adopted by one James F. Ballard of St. Louis. Mr.
Ballard seems to market a number of “patent medicines,” most of them
sold direct to the public, but some, as in the case of Campho-Phenique,
exploited to the public via the medical profession. “Herbine,” a
“marvelous preparation” that “puts the liver in healthy condition”;
“Ballard’s Snow Liniment” that when applied to wounds performs “a
perfect cure that leaves no scar”; “Dr. T. L. Stephens’ Chemical Eye
Salve” which “acts quickly in all cases” and cures “failing vision,”
are some of the numerous “patent medicines” made and sold by Ballard.
“Collins Ague Remedy,” “Swaim’s Panacea,” “Swayne’s Panacea” and
“Renne’s Pain Killing Oil” are four more of Mr. Ballard’s products, for
each of which he has pleaded guilty in the federal courts to making
false and fraudulent claims knowingly and wantonly.
If medical colleges of the better class were turning out graduates
today who could be caught by free samples of such nostrums as
Campho-Phenique, then, indeed, would the outlook for the future of
scientific medicine be a gloomy one. But they are not. The young man
or woman who goes out today from a reputable medical college is imbued
with the scientific spirit, has developed habits of straight thinking
and will not, we believe, be so uncritical as to accept at their face
value claims made for nostrums of the Campho-Phenique type.--(_From The
Journal A. M. A., Feb. 9, 1918._)
“CINCHOPHEN”: FORMERLY “ATOPHAN”
It will be remembered that the Federal Trade Commission adopted the
names arsphenamin and neoarsphenamin for the drugs first introduced as
“salvarsan” and “neosalvarsan,” respectively; the terms barbital and
barbital sodium for the substances first introduced as “veronal” and
“veronal sodium,” and the word procain as the name for the compound
first marketed as “novocain.” In issuing licenses for the use of the
patents on these drugs, the commission stipulated that the drugs
should be sold under the new American title unless the firm desired to
use a new trade designation, in which case the titles chosen by the
commission should be given equal prominence. The Council on Pharmacy
and Chemistry has cooperated with the Federal Trade Commission and
has adopted the new names as the descriptive names which appear in
New and Nonofficial Remedies. The Chemical Foundation, Inc., which
has purchased some 4,500 German-owned patents, many of them for
synthetic drugs, proposes to continue the wise policy of the Federal
Trade Commission by requiring that those who receive licenses for the
use of patents for synthetic drugs must use a common designation for
each drug selected by the foundation. “Cinchophen” has been selected
as the designation for the substance introduced as “atophan” (also
described in the U. S. Pharmacopeia under “phenylcinchoninic acid”). In
consideration of this action on the part of the Chemical Foundation,
and also because physicians found it difficult to use the pharmacopeia
name “phenylcinchoninic acid,” the Council on Pharmacy and Chemistry
has recognized the contracted term “cinchophen” as a name for the drug
introduced as “atophan.” It is hoped that physicians will support
this simplified and nonproprietary nomenclature in the same spirit
with which they adopted the terms “arsphenamin,” “barbital” and
“procain.”--(_Editorial from The Journal A.M.A., Aug. 9, 1919._)
“COLLOSOLS”: AN UNCRITICAL ENGLISH ENDORSEMENT
Under the auspices of the British Association for the Advancement of
Science, there has just appeared a report on the present status of
colloid chemistry.[247] The work has been recognized as sufficiently
important to receive the endorsement of the government Department
of Scientific and Industrial Research. Of particular interest to
physicians is the chapter on “Administration of Colloids in Disease”
written by Alfred B. Searle, “consulting chemist, Sheffield.” After a
somewhat academic generalization of colloidal drugs, the “thesis” is
devoted largely to the “Collosols”--proprietary preparations made by
the Crookes Laboratories. The “scientific” evidence presented by Searle
for colloids in medicine reads as if the advertising literature of the
Crookes concern had been considered ample source of information. Thus:
“Colloidal Manganese,” besides having been “used with remarkable and
surprising results in the treatment of coccogenic skin diseases,...
gives excellent results [in impetigo, chronic seborrheic eczema and
acute folliculitis] when employed in conjunction with intramine”! The
grave danger of the intramine therapy has been known for more than two
years, both here and abroad,[248] in fact, one author stated that in
cases of intramine injections, “the pain is undiluted torture.” In a
style as bombastic and verbose as the usual house-organ write-up, the
report recklessly details all sorts of conditions in which so-called
colloids--and particularly the “Collosol” brand--have been recommended,
but derogatory findings are conspicuous by their omission. Even Sir
Malcolm Morris is quoted as lending his name (and title) to the
endorsement of “Collosols.”
[247] British Association for the Advancement of Science. Second Report
on Colloid Chemistry. Published for the Department of Scientific and
Industrial Research by His Majesty’s Stationery Office.
[248] Ferrivine, Intramine and Collosol Iodine, J.A.M.A. =69=:841 (Sept.
8) 1917.
In the United States the medical profession has created a means whereby
physicians need not be misled by such “high” authorities as evidently
has been the case with our English confrères. Once more the value of
the Council on Pharmacy and Chemistry is strikingly manifested. What
are the facts about “Collosols”? The Council has reported that a number
of the “Collosol” preparations were not colloids at all, and “if ...
injected intravenously as directed, death might result, making the
physician morally if not legally liable”;[249] that in the cases in
which the therapeutic claims were examined, the claims were found to be
either exceedingly improbable or exaggerated; furthermore, that the
A. M. A. Chemical Laboratory found “Collosol Cocaine,” on analysis, to
contain only 40 per cent. of the claimed amount of cocain.[250]
[249] Collosol Preparations, J.A.M.A. =72=:1694 (June 7) 1919.
[250] Collosol Cocaine Not Admitted to N. N. R., J. A. M. A. 72: 1094
(April 12) 1919.
Such are the findings which have been presented to the American
physician. But the British physician is now being made the object of
an intensive advertising campaign for “Collosols,” based in part on
an uncritical, pseudogovernmental endorsement. Just so long as the
English profession will not protect itself by creating a competent
board to examine and judge proprietary medicines and to control
methods of exploitation, just so long will such extravagant and even
cruelly misleading claims continue to impede scientific progress in
therapeutics.--(_Editorial from The Journal A. M. A., Oct. 18, 1919._)
Collosol Manganese
_To the Editor_:--Has anything been published on the efficacy of
“Collosol Manganese” in malaria? I recently read the Council’s
report which indicated the fakishness of the “Crooke’s Collosols,”
but I also was told that the War Office of England had requested a
study to be made of colloidal manganese in malaria.
J. B., Columbus, Ohio.
ANSWER.--Stephens, Yorke, Blacklock, Macfie, Cooper and Carter report
in the _Annals of Tropical Medicine and Parasitology_ (Feb. 28, 1919,
p. 345) the results of their investigation for the English government
and conclude: “Collosol Manganese in the doses used is of no value
in the treatment of simple tertian malaria.”--(_Query in The Journal
A. M. A., May 3, 1919._)
COTTON PROCESS ETHER
_To the Editor_:--Please let me know what information you have
about the enclosed clipping?
E. W. Carpenter, M.D., Greenville, S. C.
_To the Editor_:--“Cotton Process Ether,” manufactured by the Du
Pont Co., has been given considerable notoriety in the lay press.
A letter of inquiry addressed to the firm elicits the information
that “Cotton Process Ether is a very highly refined Di-ethyl
Ether charged with Ethylene Gas.” ... What is your opinion of the
“Cotton Process Ether”? Has the Council on Pharmacy and Chemistry
investigated this product?
John L. Atlee, M.D., Lancaster, Pa.
_To the Editor_:--I have been waiting for some reference to the new
anesthetic referred to in the enclosed clipping, but if any has
been made in the medical press I have failed to notice it. If there
is anything of interest in connection with this item, and it is
not too much trouble, I will thank you to put me in touch with the
situation.
Holman Taylor, M.D., Fort Worth, Tex.
ANSWER.--About January 20, the “News Service” of the “E. I. Du Pont
De Nemours and Co., Inc.,” circularized the press of the country with
what it was pleased to term a “good ‘filler’”; this particular piece
of press agent work dealt with “The New Du Pont Ether.” To quote one
paragraph from the “News Item”:
The new anesthetic, which is a highly refined di-ethyl
ether, modified by the addition of gases, has the following
characteristics: (1) the property of inducing and maintaining
anesthesia with practical freedom from postoperative nausea,
and (2) the property of inducing and maintaining analgesia
(conscious insensibility to pain) as distinguished from anesthesia
(insensibility to pain plus narcosis).
The Du Pont Ether and the claims made for it are seemingly based on the
work of one man, “James H. Cotton, M.A., M.D., Toronto, Canada,” who
published an article on “Cotton Process Ether and Ether Analgesia,”
in the _American Journal of Surgery_ for April, 1919. However, Cotton
did not give the composition of the “new” ether nor, so far as we
are aware, has his work been corroborated. In view of the inquiries
received, the Secretary of the Council on Pharmacy and Chemistry asked
the Du Pont Chemical Works for the composition of the new ether. From
the firm’s reply we quote one paragraph:
“... The procedures of manufacture, and the exact composition of
our ether, we regard as confidential information which we are
entitled to retain unless a condition were to arise in which we
were unable alone to satisfy the demand for this type of ether.”
It has been recognized--and incorporated in the “Principles of Medical
Ethics”--that the use of a therapeutic agent of unknown composition
is unscientific and contrary to the best interests of the medical
profession and the public; but it is many times more serious for a
physician to employ a secret or semisecret substance as an anesthetic.
A physician using such a semisecret substance would have little defense
if the patient should die.--(_Query in The Journal A. M. A., Feb. 21,
1920._)
A Note from the Manufacturers
In the Query and Minor Notes department of The Journal of February
21, some inquiries from physicians relative to “Cotton Process Ether”
were answered. In referring to the composition of this product it was
stated that the secretary of the Council on Pharmacy and Chemistry had
asked the manufacturers, the Du Pont Chemical Works, for information on
this point and one paragraph from the firm’s reply was quoted. Another
paragraph from the same letter was omitted; and to this omission the
manufacturers took exception, expressing the opinion that by it The
Journal led its readers to infer that the concern had “refused to
furnish any information whatever” regarding the composition of the
ether. The following paragraph, italicized as in the original letter,
is the one in question:
“_Cotton Process Ether contains no components which do not occur
in other anesthesia ethers._ Its peculiar properties result from
the thorough methods taken to exclude harmful impurities, such as
aldehydes, peroxides, traces of acids, carbon monoxide, sulphur
compounds, etc., and to include carefully regulated quantities
of only such of the usual components as we have found to give
distinctly beneficial properties to the ether. We are willing to
state that in this class we consider properly prepared ethylene
of greatest importance, but we have not announced which of the
beneficial components of anesthesia ether we include in our ether,
or the amount of such components.”
As the quotation shows, the paragraph is informative in a negative
rather than in a positive way in that it states what Cotton Process
Ether _is not_ rather than what it _is_. Since that time, however,
the manufacturers have notified The Journal that they have definitely
decided to present Cotton Process Ether to the Council on Pharmacy and
Chemistry for consideration and that in preparing the data required by
the Council will define Cotton Process Ether as follows:
“An improved anesthesia ether consisting of highly refined diethyl
oxid (C₂H₅)₂O, plus approximately two volumes of ethylene (C₂H₄),
1/2 volume of carbon dioxide (CO₂) and 1 per cent. by weight of
ethyl alcohol.”--(_From The Journal A. M. A., May 22, 1920._)
DIONOL
“Dionol” is advertised to physicians by the Dionol Company of
Detroit. If one takes the word of the manufacturers, the therapeutic
possibilities of Dionol are apparently limited only by the blue sky.
Even the company admits that “the unprecedented range of action” of
this marvel “may come as a surprise.” A glance over the published “case
reports” confirms the inference. From “Bed Sores,” “Bubo,” “Catarrh”
and “Circumcision” through “Croup,” “Deafness,” “Dysmenorrhea”
and “Eczema,” including “Endometritis,” “Erysipelas,” “Gastritis”
and “Hemorrhoids,” not omitting “Osteomyelitis,” “Otitis Media,”
“Pneumonia” and “Ptomaine Poisoning,” down through the pathologic
alphabet to “Quinsy,” “Sciatica,” “Spinal Curvature,” “Varicose Veins,”
and “Whooping Cough” one concludes that here at last is a catholicon
indeed.
What is Dionol? First it should be said that the preparation comes in
two forms: as an ointment and as an emulsion. The ointment, so declare
the manufacturers, “is _always_ required”; the emulsion may be used
“as an auxiliary treatment.” The Dionol “literature” when stripped of
the verbal camouflage with which it abounds may be said to propound
the following theories and propositions: First, that the nerves of the
body are electric conductors insulated from the surrounding tissues by
the nerve sheaths; second, that inflammation breaks down the insulation
with the resultant escape of the current and an interference with the
normal metabolic action of the cells; third, that Dionol, when applied
to the body, penetrates the tissues, “coating the cells and with them
the nerve sheaths with a nonconducting layer which is sufficient to
insulate the nerve sheaths and stop the leak.”
So much for the theory on which the alleged action of Dionol is based.
Dionol itself is a sort of glorified petrolatum. Not, of course, that
the manufacturers describe it in any such crude and understandable
language. According to the company, Dionol is “composed of pure
hydrocarbons, especially selected with regard to specific gravity,
viscosity and other necessary physical properties” which has been
“perfectly _deionized_ by our special scientific process under the
Baines Method.” It appears, from further reading, that ordinary
petrolatum will not “turn the trick”; presumably because it does not
overcome the human short circuits which the Dionol Company declare are
always present in inflammation. When, however, the petrolatum has been
subjected to the “Baines Method” it achieves, it seems, an esoteric
value that puts to shame its plebeian origin.
The whole thing is very simple. To those physicians that like this sort
of thing this preparation should make a strong appeal.--(_From The
Journal A. M. A., Jan. 26, 1918._)
Glorified Petrolatum
An Indiana physician sends us in a batch of leaflets detailing the
marvels of “Dionol” and thus comments:
“I received the enclosed in the mail today and I am puzzled,
perplexed and astounded. I had formed the opinion that the
profession was getting better; that it was more scholarly than
formerly when the two course school was still in existence and any
one could matriculate; that it was no longer possible for a ‘patent
medicine’ manufacturer to palm off his wares on us. After reading
this stuff and realizing that such methods must be remunerative,
I am deeply humiliated. Is it possible that educated physicians
respond to this kind of advertising? Or has some one perpetrated a
joke on me? If the profession can be thus successfully exploited
one can no longer wonder at the following which every new ‘ic’ and
‘ism’ acquires.”
It is a pity that the medical profession generally does not react to
the Dionol and similar advertising as does our correspondent. As the
concern continues to do business, the presumption is that at least
some physicians are using Dionol. As was pointed out in The Journal
of Jan. 26, 1918, Dionol seems to be a glorified and esoteric form
of petrolatum. The exploitation of Dionol is based on the following
theory: (1) The brain is a generator of neuro-electricity; (2) the
nerves are the conductors of this electricity; (3) the nerve sheaths
are the insulator; (4) wherever there is local inflammation the
nerves are short circuited, due to a breaking down of the insulation
resistance of the nerve sheath; (5) this results in “an escape
of neuro-electricity;” (6) Dionol coats the nerve sheaths with a
nonconducting layer and this restores the insulation and “stops the
leak.”
Whether this ingenious theory was invented to lend an air of
verisimilitude to an otherwise bald and unconvincing tale and give a
“reason for being” for Dionol or whether Dionol was first invented
and it became necessary to evolve a theory that would give some
plausibility to the claims made for this etheralized petrolatum, we are
unable to say. In any case the theory and the product are exploited
together.
Among the material sent in by a correspondent are some “Dionol Case
Reports.” Neither the names nor the addresses of the physicians making
these reports are given, but the company states that they may be had
“on request.” One special “report” is featured under the heading
“Infected Wound. Striking Results After United States and French
Government Army Surgeons Failed” is signed “Dr. W.” It is dated July
19, 1919. A few months ago the Dionol Company was sending out this same
testimonial with the full name and address of the “doctor” giving it.
Investigation showed that the “doctor” in question was an osteopath
whose specialties, according to his advertisement in his local
newspaper, are “Catarrhal Deafness and Hay Fever, Acute and Chronic
Diseases”! In this connection it is worth noting that investigation of
some of the earlier testimonials sent out by the Dionol concern and
alleged to have been given by “doctors” showed that the gentlemen in
question were “drugless healers.”
As a “true indication of the value which the medical profession is
placing on Dionol” the Dionol Company has published the names of some
physicians who, it is alleged, have used the preparation.--(_From The
Journal A. M. A., Feb. 7, 1920._)
THE ELI PRODUCTS OF ELI H. DUNN
Physicians are receiving some miscellaneous advertising matter from a
concern that seems to operate under various names such as “E. H. Dunn &
Co.,” “Eli H. Dunn,” “Eli Laboratory,” etc. The concern is located at
3820 Main St., Kansas City, Mo. One Journal reader, who is evidently
not greatly impressed by this material, forwards the stuff to us with
the laconic request: “Will you please give me your opinion on this
junk?”
The “junk” referred to comprised, in part, an advertising leaflet on
“Eli 606 Capsules,” another leaflet on “Eli Vaginal Capsules,” still
another on “Eli ‘Vim’ Restorative;” then there was reference to the
inevitable nostrum for intravenous use: “Ampoules Eli Venhydrarsen.” A
four-page leaflet, headed in large and very black letters “Confidential
Guide to Live Wire Physicians Only,” expressed its key-note in the
opening paragraph:
“How to make MONEY as well as REPUTATION in the treatment of all
CHRONIC AILMENTS and all types, forms and sequella of VENEREAL
diseases.”
The “Eli ‘Vim’ Restorative” is said to be a “tonic aphrodisiac.” The
“action” of the product is to “Arouse Sexual Ardor and Desire. Influx
blood supply to the genital organs.” A postscript to the “Guide” urges
physicians:
“If you do not already use Intravenous Serums, by all means get an
outfit, if for no other reason than to meet the popular DEMAND.”
A “Special Note” in the “Confidential Guide” advises physicians who
“have to deal with Hysteria” to “write the Author of this Guide, who
will explain by personal letter a method of cooperation by which such
Convulsions may be At Once and forever stopped.... There will be $100
for You from every case treated.” One physician wrote to the “Author of
this Guide”--Eli H. Dunn, M.D.--asking for further information on this
treatment for hysteria. He received in reply two letters both signed
Eli H. Dunn; one was to be shown to the patient, the other was for the
doctor’s own information. The letter for the patient to see described
the marvelous effects of “Dunn’s Intravenous and Restorative Treatment”
in hysteria and recommended it “with the utmost confidence in every
case able to pay you the fee commensurate with the service you render.”
Then followed these two paragraphs:
“The cost of the treatment when administered by yourself is $300
CASH WITH ORDERS which includes one complete outfit and technique
for administering.
“Should you call me personally in consultation an additional fee
of $150 per diem covering the time I am away from my Kansas City
office; fees to be collected and held until I arrive.”
The letter that was intended only for the doctor’s eye declared:
“You are to have $100 of the fee and $50 of the per diem.”
It explained that the “complete outfit” referred to in the “patient’s
letter” would “consist in part of a tube of intravenous medication” and
doses of “Restorative Capsules” and “Eli 606 Capsules.”
Eli H. Dunn seems to have had a somewhat varied and spectacular career.
After being graduated in 1885 he apparently started practice in Orion,
Ill. During the nineties he was practicing at Elma, Iowa, and about
1900 he seems to have moved to Kansas City, Mo. During 1906 and 1908,
he also had an additional office at Denver, Col. About this time he was
exploiting “Dunn’s Uterine Evacuant” which was “a strictly legitimate”
product which could “be injected within the uterus with perfect safety
and immediate effect.” This stuff was advertised both from the Kansas
City and the Denver offices. The “Personal Column” of a Kansas City
paper in 1910 carried the message to “Ladies” that “Dr. Dunn” was a
“Regular physician for women only,” Dunn’s violation of the postal laws
in 1911 and of the federal Food and Drugs Act in 1912 need not be gone
into at this time.
The Journal would feel like apologizing for devoting space to such a
preposterous scheme were it not for the fact that physicians, being
human, sometimes “fall for” preposterous schemes. Some, we know, have
nibbled at Dunn’s bait; others may do so. The gross commercialism that
permeates the advertising matter sent out by Dunn again emphasizes
the fact that the fad for intravenous medication offers an attractive
field for those who would exploit our profession.--(_From The Journal
A. M. A., Nov. 22, 1919._)
GLOVER’S CANCER SERUM
Scores of letters have reached--and are reaching--The Journal office
similar in effect to the following:
“I am enclosing ‘literature’ received from the ‘T. J. Glover
Research Laboratory.’ Though purporting to come from Toronto, where
the $25.00 are to be sent, if you please, the envelope bears the
448
New York postmark.”
The above is from New Jersey while the two following are from Michigan
and Illinois, respectively:
“Have you any information in regard to this party and his treatment
for cancer? This is the first I have heard of any such work having
been done. One wonders if it is presented in good faith or if the
money god has overcome the gentleman’s scientific spirit.”
“Is this just one more of them? Why a roan horse? Some people might
want serum from a nice bay or calico cow pony.”
The literature referred to comes in an envelop bearing the name of
“T. J. Glover, Research Laboratory, Toronto, Canada,” but mailed,
apparently, from New York City. The enclosures are a single sheet
circular signed Thomas Joseph Glover and entitled “Etiology of Cancer,”
a “Directions” slip and a card quoting prices. In the circular Dr.
Glover states that he has prepared a serum from immunized horses,
“between ages of seven and nine years, of the roan type,” and has
injected this intramuscularly “into patients in the advanced stages of
cancer and noticed that it has a specific action on every known type of
cancer.” Further:
“Up to the present time I have apparently cured cancer of the face,
eye, nose, lip, mouth, tongue, stomach, bowel, bladder, breast and
uterus.”
In addition to the circular, was a small leaflet giving directions for
the injection of the serum and also a card bearing Dr. Glover’s name
and Toronto address and reading:
+------------------------------------------------------------+
| This is to advise you that DR. T. J. GLOVER’S Serum |
| for the treatment of cancer can now be had by |
| application to office at above address. |
| |
| PRICE FIVE DOLLARS PER TREATMENT. FIVE TREATMENTS |
| MINIMUM NUMBER SENT AT ONE TIME. |
| |
| Send money by Post-Office Money Order or Certified Cheque. |
| |
| DIRECTIONS FOR TREATMENT WITH EACH ORDER. |
+------------------------------------------------------------+
This advertising material, which is evidently being widely circulated
in the United States, would indicate that the Glover Research
Laboratory had received a permit from the United States Public Health
Service licensing the interstate sale of this serum in the United
States. No such license has been issued.
The Journal briefly reported in the department of Medical News, Oct.
30, 1920, that the Academy of Medicine of Toronto had appointed a
committee to investigate the claims made for the Glover “cancer serum.”
In the meantime, the most charitable thing that can be said is that the
“treatment” is in the experimental stage and the reported results have
not been corroborated by independent investigators.--(_From The Journal
A.M.A., Jan. 1, 1921._)
The Toronto Academy of Medicine Reports Unfavorably on
Glover’s Cancer Serum
The method of exploitation of the alleged cancer serum being put out
by Dr. T. J. Glover of Toronto, Canada, was briefly discussed in this
department of The Journal for January 1. At that time it was pointed
out that the medical profession of the United States was being widely
circularized by Dr. Glover and that, while the letters purported to
come from Toronto, they were, in fact, mailed from New York City. Since
this article appeared the circularization seems to have continued
undiminished and physicians in various parts of the United States have
sent in the Glover advertising material. Oddly enough, the matter now
sent out, while identical in every respect with that dealt with in
the previous article, bears a different return address on the back of
the envelop. The envelops are the same; but the legend “T. J. Glover
Research Laboratory, 538 Jarvis St., Toronto, Canada,” has been crudely
crossed out and there has been substituted by means of a rubber stamp
the legend “MRS. STEWART, 309 W. 54th St., New York.” Still later
letters have been modified to the extent that the letters “RS” of
“MRS.” have been cut out of the stamp and it now reads “M . STEWART.”
There has now come to hand a report just published by a special
committee appointed by the council of the Academy of Medicine, Toronto,
to investigate the Glover Serum. The report of this committee may be
summed up by one of its closing paragraphs, which reads:
“The data which your committee has been able to obtain have not
convinced it that the results of treatment obtained by the use of
Dr. Glover’s serum are better than those obtained by similar methods
introduced by others, and which have ultimately disappointed the
hopes entertained of them.”
The committee’s report deals with the claims that Dr. Glover has made
for his serum, both experimental and clinical. It seems that Dr.
Glover has claimed that, experimentally, he had (1) cultured cancer
cells and from these cells had isolated and cultured an organism which
he declared was confined to, and present in, every type of cancer;
(2) produced cancer in a number of animals by inoculation with these
cells and organisms; (3) obtained a serum--from a horse that had been
injected with cultures of these cells and organisms--which, when
injected into experimental animals rendered them immune to inoculation,
and (4) produced improvement or cure in cases of human cancer by the
injection of his serum. The committee reported that it was unable
to obtain any evidence to substantiate Dr. Glover’s claims on the
experimental aspect of the question as Dr. Glover had refused to permit
representatives of the committee to visit his laboratory; had refused
the request of the committee to be allowed to examine his cultures and
experimental material; had not acceded to the request of the committee
that he demonstrate his ability to culture cancer cells and organisms
and to produce cancer by inoculation or to immunize animals against it.
The committee attempted also to collect information which would
enable it to pass on the clinical claims made by Dr. Glover, first,
as to whether he has succeeded in producing cures, either regularly
or occasionally, in cases definitely established as cancer and,
second, to enable the committee to decide whether his serum in cases
definitely established as cancer produces improvement beyond that which
occasionally occurs spontaneously or under palliative measures. On both
of these points, the committee reported that it found no evidence to
warrant the hope that a specific cure for cancer has been discovered by
Dr. Glover or that the serum had produced a cure in any case definitely
established as cancer.
It should be understood, that the committee’s investigations and
findings were completed before the present advertising campaign of the
Glover serum was initiated.--(_From The Journal A.M.A, Feb. 5, 1921._)
GLYCO-THYMOLINE AND POLIOMYELITIS
One characteristic of the “patent medicine” business is that it trades
on fear. Should an epidemic occur the market is flooded with new
nostrums purporting to cure or prevent the disease in question, while
the manufacturers of older “patent medicines” revamp their advertising
so as to make it appear that their preparations are all that stand
between the scourge and the public. One has but to remember “Peruna’s”
exploitation of the yellow fever epidemic in New Orleans some years ago
and the way in which the exploiters of “Pond’s Extract” played on the
fears of the public at the time of the former meningitis epidemic in
New York City.
At present the public is much exercised over the epidemic of infantile
paralysis. Anticipating that the nostrum fraternity would attempt to
reap a golden harvest from the public distress, the federal officials
issued a bulletin of warning on the subject. Naturally, the bulletin
was addressed to the lay public, the government assuming that
physicians knew enough to avoid being misled by any such advertising
campaigns. Apparently, the assumption is too broad. At any rate, the
manufacturers of “Glyco-Thymoline” are circularizing physicians, one of
whom writes as follows:
_To the Editor_:--I am enclosing circular letter that I received
this morning which seems to me almost a crime. I do not suppose
that there is any way to prevent anything of this sort, but it is
certainly a shame to attempt to deceive people in this way. As I
recollect, Glyco-Thymoline is almost inert, practically no more
efficient than Dobell’s Solution.
E. Fletcher Ingals, M.D., Chicago.
The circular letter referred to was on the stationery of Kress & Owen
Company, manufacturers of Glyco-Thymoline. It read:
_Dear Doctor_:--Regarding Infantile Paralysis, it is conceded that
the source of infection is through the Nose, Mouth and Throat.
Taking this measure to be correct, we believe that there is no
safer prophylactic measure than the use of Glyco-Thymoline, with
three parts of water, as a mouth, tooth and nasal wash, by means of
the K. & O. Nasal Douche and the toothbrush.
Glyco-Thymoline tends to promote exosmosis, and prevents the
absorption of the germ or toxic matter.
We would be glad to send you samples of both Glyco-Thymoline and
the Douche should you so desire.
With best wishes, we beg to remain,
Yours very truly,
Kress & Owen Company.
Glyco-Thymoline has been discussed in these pages. A report of the
Council on Pharmacy and Chemistry pointed out that this “patent
medicine” is simply a weak antiseptic, so feeble that even in full
strength it does not kill _Staphylococcus aureus_ in four hours
and is of little, if any, greater therapeutic value than sterile
salt solution. Yet, Glyco-Thymoline has been recommended by its
manufacturers, either directly or inferentially, for such diseases
as diphtheria, ophthalmia neonatorum and consumption. Today its
manufacturers put it forward as one of the safest prophylactic
measures against infantile paralysis and have the effrontery to make
this suggestion, not to the uninstructed public but to the medical
profession. Presumably, as a business organization, the concern
believes it will convince a sufficient number of physicians of the
therapeutic efficacy of its product to pay for the cost of this
advertising campaign. If it appraises the situation correctly there
need no longer be any wonder expressed that in the recent suit against
The Journal, “patent medicine” makers were able to enlist the help of
medical men.--(_From The Journal A. M. A., Sept. 16, 1916._)
GLYKERON: COLD STORAGE TESTIMONIALS[K]
[K] Glyco-Heroin
The law which limits the length of time that food products may be kept
in cold storage could with advantage have its scope extended to include
“patent medicine” testimonials. Physicians recently received through
the mails--at a time when the mails were frightfully congested with
Christmas business--a sixteen page pamphlet sent out in a plain envelop
as first class matter. The caption of the pamphlet reads: “Cough and
Its Treatment in Pulmonary and Laryngeal Tuberculosis: By Henry Levien,
M.D., While Medical Director and Physician-in-Charge of the Liberty
Sanitarium, Liberty, N. Y. From the _Buffalo Medical Journal_.” The
pamphlet is devoted to the alleged virtues of that dangerous and widely
advertised nostrum, “Glyco-Heroin (Smith),” whose more recent and
less descriptive name is now “Glykeron.” Physicians might assume, and
doubtless will assume, from the pamphlet that this reprint represents a
recent pronouncement on the subject with which it deals. The facts are
that the “Liberty Sanitarium” has, apparently, been out of existence
for at least fifteen years, while the article itself originally
appeared more than eighteen years ago--September, 1901. One of many
physicians who sent in the copies received called attention to the fact
that he had left the address to which the pamphlet was directed, more
than six years ago. Even at that, the mailing lists of the concern that
sells this heroin-containing nostrum are more than twelve years ahead
of its “clinical reports.”--(_Editorial from The Journal A. M. A., Jan.
17, 1920._)
GRAY’S GLYCERINE TONIC: “WHOSE BREAD I EAT HIS SONG I SING”
Last September the United States Department of Agriculture issued
a press bulletin describing the work of the Bureau of Chemistry in
prosecuting the venders or manufacturers of fraudulently exploited
“patent medicines.” At the end of the bulletin was a tabulated list of
“other preparations against which the government’s charge that they
were falsely or fraudulently labeled was sustained by the federal
courts.” Tucked away in the list was a product often euphemistically
described as an “ethical proprietary” but none the less essentially
a “patent medicine”--“Gray’s Glycerine Tonic.” The editor of the
_Atlanta Journal of Medicine_, apparently not having read the bulletin
with any great degree of care, published it verbatim. Thus it was
that the _Atlanta Journal-Record of Medicine_ for September, 1915,
presented the interesting sight of a half-page advertisement of “Gray’s
Glycerine Tonic” in the same issue that contained the government’s
article classifying “Gray’s Glycerine Tonic” among the false and
fraudulent products! What happened? In the very next issue the _Atlanta
Journal-Record of Medicine_ apologized thus editorially:
“In our September issue, Gray’s Glycerine Tonic Comp. was
inadvertently included in a list that seemed to be under the ban
of the Government and very likely an injustice has been done
the Purdue Frederick Company which we desire to undo as far as
possible.”
Did the editor mean by “inadvertently included,” that he would have
omitted “Gray’s Glycerine Tonic” from the government’s list had he
noticed it in time? If so, on what grounds? It is a fact that “Gray’s
Glycerine Tonic” was one of the “Fifty Falsely Labeled Medicines”; it
is also a fact that it is one of the products that government officials
and the federal courts have declared to be sold under claims that are
“false, fraudulent and misleading.” If “Gray’s Glycerine Tonic” was
fraudulently exploited--and the government and the courts have so
declared it--why is it necessary for the editor of a medical journal to
apologize to his subscribers for having told them so?--(_Editorial from
The Journal A. M. A., Jan. 1, 1916._)
HAGEE’S CORDIAL OF COD LIVER OIL
“Under the deceptive heading ‘Making Cod Liver Oil Palatable,’ the
_Charlotte Medical Journal_ in its December issue prints a boost for
‘Cord. Ext. Ol. Morrhuae Comp. (Hagee),’ or, as it is generally known
to the drug trade, ‘Hagee’s Cordial of Cod Liver Oil.’
“The boost intimates that this is a preparation in which cod liver oil
has in some way been rendered palatable, and then goes on to say that
this is a cod liver oil product which has not suffered the least loss
of those essential elements which make the crude oil such a high-class
reconstructive.
“At first sight one might question whether a cod liver oil product
which contains absolutely no cod liver oil had not suffered the loss
of essential elements. But a closer reading discloses a significant
qualification, namely, the phrase, ‘those elements which make the
crude oil such a high-class reconstructive.’
“The boost is misleading from beginning to end. The manufacturers have
not succeeded in this preparation in ‘making cod liver oil palatable,’
nor does their preparation in any way possess the virtues of cod liver
oil. These claims have again and again been refuted, but they continue
to be published--at a price but rarely in reputable medical journals.”
The above is quoted from the _Weekly Bulletin_ of the Department
of Health of the City of New York. The Bulletin is issued for the
enlightenment of the public.--(_From The Journal A. M. A., Jan. 8,
1916._)
HYPNO-BROMIC COMPOUND
A physician in Vermont writes:
“This is simply a word of inquiry--and of possible warning to
other practitioners--regarding a preparation known as Hypno-Bromic
Compound manufactured by H. K. Wampole & Co. This compound is
dispensed by druggists without prescription and contains in each
ounce:
“Cannabis indica 1 gr.
“Morphin 1/4 gr.
“Potassium bromid 48 gr.
“Hyoscyamus 1 gr.
“Chloral hydrate 96 gr.
“I have at the present time three young women who are addicts to
this preparation as the result of thoughtless prescriptions from
physicians. This mixture evades the working of the Harrison Act and
may be dispensed freely at the discretion of the druggist and, as
a result, these three cases of mine have been able, by visiting at
the various drug stores in town, to keep an ample supply on hand at
all times.”
“Hypno-Bromic Compound” is more than an unscientific mixture; it is
a dangerous product and should not be sold indiscriminately over the
drug counter. Before the Harrison Narcotic Law went into effect,
“Hypno-Bromic Compound” contained half a grain of morphin sulphate to
the ounce instead of its present one-fourth grain. Physicians remember
that Section 6 of the Harrison law contains a joker--put over by
the “patent medicine” interests--that exempts proprietary remedies
containing one-fourth grain of morphin or less to the ounce from the
restrictions of that act. While it is illegal for a physician to write
a prescription which contains morphin, no matter how small the amount,
unless he conforms in all ways to the requirements of the Harrison
Narcotic Law, “patent medicine” concerns can sell indiscriminately
nostrums containing morphin up to this amount and the public can buy
them without let or hindrance. No reputable druggist would sell a
layman over 700 grains of chloral hydrate or 2 grains of morphin or 8
grains of extract of cannabis indica, without a prescription, yet, the
druggist may hand over 8 ounce bottles of Hypno-Bromic Compound which
contain 768 grains of choral hydrate, 2 grains of morphin sulphate, 8
grains of extract of cannabis indica, 8 grains of hyoscyamus and 384
grains of potassium bromid! Physicians who prescribe such products as
Hypno-Bromic Compound and druggists who indiscriminately sell such
stuff are disgracing two honorable professions.--(_From The Journal
A. M. A., Feb. 7, 1920._)
INTRAVENOUS COMPOUND (LOFFLER)
Its Composition and the Peculiar Methods by Which It Is Exploited
For some time past inquiries have been received regarding Charles Lyman
Loffler, his Post-graduate Course in Intravenous Therapy and especially
relative to “Intravenous Compound (Loffler).” For instance, a physician
writes:
“Can you tell me anything about the Physicians Drug Syndicate....
They are pushing the sale of Thymozene and offering One Hundred
Dollars’ worth of stock fully paid and non-assessable, free to
those sending in their order, and also a copy of Dr. Loffler’s
Lectures on the Blood.”
And from another physician:
“What do you know of Charles Loffler, M.D., and his Intravenous
Compound? A few evenings ago a man who appeared to be about 40
years old came to my office and tried to interest me in the
above-mentioned article; he claimed to be Dr. Charles Loffler
of Chicago. With him was a young lady whom he introduced as
Miss B----. Miss B---- said that she had been with Dr. X---- [a
physician of high standing in Los Angeles] for two months and
that he was using the Intravenous Compound; also quoted other
physicians.... His whole layout looks quackish, and were it not for
the fact that he showed me a letter that appeared to be from Dr.
X----, I should not have given him a second thought.”
And this also:
“Charles Loffler, M.D., or his agent was traveling around inducing
one M.D. in each town to take up his methods of blood examination
and treatment and with a little advertising of blood examinations
free the doctor selected gets quite a run of patronage.”
Another physician writes:
“My attention has been called by another physician to Loffler’s
Intra-Venous Compound. May I trouble you to give me any information
that you may have with regard to its composition and its value as a
therapeutic agent?”
C. L. Loffler does business from Rooms 1101-1102, Venetian Bldg.,
Chicago, the location of the “Intravenous Chemical Co.,” the
“Physicians Drug Syndicate” and the “Ma-Oze Chemical Co.” Of these,
more later. The Journal has in its files a large amount of material
regarding Loffler. A brief résumé of that part of the material dealing
with Loffler’s professional activities will be given for the purpose
of allowing physicians to evaluate the scientific status of Loffler’s
“Lectures,” “Post-Graduate Courses,” his therapeutic “discoveries” and
his products.
It seems that Loffler was reared in Yankton, S. D. In 1898-1899,
Loffler was a senior student at John Creighton Medical College, but,
for reasons that need not be gone into here, he was never graduated.
He received a diploma from Barnes Medical College in 1900, and in the
same year was licensed to practice in South Dakota. In 1902 he was at
Le Mars, Iowa; in 1904 his name appears in the medical directory, under
Sioux Falls, S. D., as “Specialist in Chronic Troubles.”
THE INTRAVENOUS COMPANY IN COLORADO
Charles L. Loffler’s “specialty” is “Intravenous Medication.” In
1912 and 1913, as the Intravenous Company of Colorado Springs, he
was sending out a booklet entitled “Consumption.” This described
the alleged marvelous results to be obtained in the treatment of
tuberculosis by the use of “Intravenous Compound”; there was also
a side line, “The Loffler Internal Bath Plate.” At that time the
administration of “Intravenous Compound” was recommended intravenously,
hypodermically, by rectum, by mouth and even by insufflation. When the
stuff was to be given by rectum, the recommendation was made: “First
wash out the bowels with a preliminary injection of two or three quarts
of warm water, using for this purpose the Loffler Internal Bath.”
In 1913 Loffler sought a larger field for his peculiar talents and left
Colorado Springs. After a short stay in Denver he is next found in
Minneapolis, where he was also “engaged in the practice of intravenous
therapy” and, incidentally, seems to have been an organizer and manager
of a common law concern known as the Automatic Thrasher Co.
THE PHYSICIANS’ DRUG SYNDICATE
In 1919 we find Loffler in Chicago as president of the “Physicians Drug
Syndicate.” This concern--another common law organization--had for
its vice president one A. E. Erling, M.D., and for its secretary and
treasurer, Arthur C. Hanson. Erling was discussed[251] in an article
that appeared in The Journal, July 5, 1919, on the egregious “Allied
Medical Association of America” of which organization C. L. Loffler was
“President” in 1918.
[251] Here is what _The Journal_ published on Erling:
A. E. Erling according to the stationery, is “Chairman” of “Censors.”
Our records fail to show that Erling ever graduated in medicine.
The Health Department of Milwaukee, however, says that Erling, when
interviewed, claimed to have “a diploma from the German Medical College
of Chicago, but refused to show or present the same.” The American
Medical Directory has this item:
_German Medical College, Chicago. Chartered Dec. 28, 1891, by
Johann Malok. Fraudulent. Extinct._
A few years ago Erling was in La Crosse, Wis., and in 1908 a circular
letter bearing his name and picture was sent out, from which the
following extracts are taken. Capitalization as in the original:
“Dear Friend:--Permit me to call your attention to the fact that
Dr. A. E. Erling, the eminent specialist, after many years of
travel, practice and medical research, has given up his extensive
road practice and severed his connection with the several medical
institutes which have heretofore occupied considerable of his
attention.... Dr. Erling’s success in the treatment of all CHRONIC
DISEASES IS TRULY REMARKABLE. NERVOUSNESS, ALL BLOOD DISEASES,
RHEUMATISM, DISEASES PECULIAR TO WOMEN; CATARRH, DEAFNESS, CHRONIC
CONSTIPATION ... APPENDICITIS ... PILES, STOMACH TROUBLES, PARTIAL
PARALYSIS, etc., give way as if by magic under his skilful method
of treatment.... Understand, please, that Dr. Erling DOES NOT
ACCEPT A CASE FOR TREATMENT unless he can PROMISE A SPEEDY AND
POSITIVELY PERMANENT CURE.”
_The Journal_ also has in its files advertisements (vintage of 1915),
from some Wisconsin country newspapers; which notify the afflicted that
“Drs. Erling and Karass, the expert German Specialists,” could be seen
in their offices in the “Schlegel Hotel,” the “Schlitz Hotel,” etc., as
the case might be. Whether one of these “German Specialists” was Dr.
Arnold E. Erling, _The Journal_ does not know. Official medical records
fail to show, at least, that there is any other Erling in the state of
Wisconsin.
Hanson, the secretary and treasurer of the Physicians Drug Syndicate,
is said to have hailed originally from Minot, N. D., where he was in
the drug business. His name appears in the Propaganda files as the
manager of the Ma-Oze Chemical Co. of Minneapolis, which, in October,
1919, was advertising in a daily paper of that city:
“Protect yourself against influenza. Don’t let the germs get a
foothold in your system. Kill them with Ma-Oze Antiseptic Powder.
Use it as a gargle. It is ... sure death to all kinds of disease
germs.”
In a preliminary statement sent out by Hanson in the early part of 1919
it seems that the Physicians Drug Syndicate was conceived “primarily
to supply physicians with a product to be used in Leucorrhea and
personal cleanliness of women.” This product, apparently, was the
Ma-Oze of influenza fame in Minneapolis. It was to be put out, however,
under the name of “Thymozene,” which, “packed in 4 ounce unlabeled
carton for dispensing,” would “show nearly 100 per cent. profit to the
organization over the profit which you make if you dispense your own
drug.”
THYMOZENE, FREE STOCK--AND EVERYTHING
In October, 1919, the Physicians Drug Syndicate was circularizing
physicians in Iowa trying to get them to send in $6 for “1 Dozen
Thymozene 4 oz.” For this $6 the doctors were to get, in addition
to the marvelous Thymozene, the following rights, privileges and
emoluments:
1. A free Post-Graduate Course in Intravenous Therapy by Dr. Charles
Loffler.
2. A gift of $100 worth of stock in the Physicians Drug Syndicate.
3. A copy of Dr. Loffler’s Lectures on Blood.
4. The privilege of purchasing future supplies of Thymozene “at
wholesale prices less discount of 33-1/3 per cent.”
The letter making these offers mentioned incidentally:
“Besides our product Thymozene we have been forced to add a Uterine
Wafer to be used in connection with hot Thymozene douches in
Leucorrhea. These wafers are simply miracle workers.”
In addition to this circular letter there was a membership blank
leaflet detailing the marvels of “Thymozene.” There was another leaflet
headed in very large, black type “Influenza” and recommending “Ma-Oze
Antiseptic Powder” or “Thymozene” for this condition. Still another
leaflet accompanying it lauded “Intravenous Compound (Loffler)” and
reprinted laudatory puffs of this preparation that were credited to
H. H. Witherstine, M.D., Rochester, Minn., Joseph B. Klinehans, M.D.,
Chicago, and the “Loring Park Sanatorium” of Minneapolis.
In addition to the Intravenous Compound (Loffler) there is, of
course, certain “apparatus for the giving of the treatment” which the
Intravenous Chemical Co. supplies. The “compound” must be given just
so, and the Intravenous Chemical Co. “reserves the right to refuse to
supply any physician with Intravenous Compound (Loffler) who, either
through lack of proper apparatus or proper care in preparation of
solution, or for any reason, uses it in such a manner that will cast
discredit upon it.”
The complete apparatus, including 2 ounces of Intravenous Compound
(Loffler), sells for $24. What is Intravenous Compound? Apparently,
nobody knows except Charles L. Loffler, who asks physicians to
inject--and we regret to say some are injecting--this nostrum of
unknown composition into the veins of their patients. To a physician
who had raised the point of secrecy Loffler wrote in part:
“I am sure that you will agree with me that it is far better to
place this treatment in the hands of competent physicians, such as
Dr. Witherstine, and many more whose names I will gladly send you,
and to protect the honest and competent doctor who investigates
and takes up the work, than to publish the formula and give to the
unscrupulous a chance to try to make the product and no doubt to
claim to cure disease that is beyond hope. The formula is not kept
secret for profit ... but is so kept upon the advice of a number
of good men who have the interest of the doctor at heart.... I
am willing and anxious to place the product and the results in
thousands of cases before the A. M. A. on the one condition that
the formula shall be kept secret for the benefit of the reputable
physician.”
In another letter written more recently to a physician who called
attention to the secrecy of the nostrum, Loffler wrote:
“The Intravenous Compound contains approximately 58 per cent.
oxygen, 12 per cent. chlorine, 16 per cent. potassium, 9 per cent.
sodium and 5 per cent. boron. I have no hesitancy in giving it, and
it was due to an incompetent man in this office that this was not
given fully in the booklet. He made the changes without my consent
and has caused me to answer many inquiries by physicians.”
A seeming frankness is a trick as old as nostrum exploitation itself.
Loffler’s “formula” is meaningless. A quack who was putting out a
mixture of 1 part baking soda and 2 parts common salt might with equal
frankness say that his marvelous combination contained approximately
35.4 per cent. sodium, 4.8 per cent. carbon, 19 per cent. oxygen, 40.4
per cent. chlorin, and 0.4 per cent. hydrogen.
In order that the profession might know more about this product a
specimen was turned over to the A. M. A. Chemical Laboratory for
analysis. Here is what the chemists report:
CHEMISTS’ REPORT
“One original 2 ounce bottle of ‘Intravenous Compound (Loffler) for
Intravenous Use’ was submitted to the Association’s Chemical Laboratory
for examination. According to the label, the product is sold by the
‘Intravenous Chemical Co., Chicago.’ The bottle contained a white
granular substance, which appeared as if the ingredients had been
fused together. The product responded to tests for sodium, potassium,
chlorate, borate and nitrate. As this same set of chemical radicals was
found by Puckner and Hilpert (J. A. M. A., May 22, 1908, p. 1706) to be
present in ‘Oxychlorin’ and ‘Zyme-oid,’ a quantitative comparison of
‘Intravenous Compound (Loffler)’ was made.
“The analysis indicated that all three products are essentially the
same:
INTRAVENOUS
OXYCHLORIN, ZYME-OID, COMPOUND,
Per Cent. Per Cent. Per Cent.
Potassium (K+) 12.26 13.50 13.79
Sodium (Na+) 8.20 9.84 9.82
Boric acid anhydride (B₂O₃) 18.63 13.42 15.20
Chlorate (ClO₃-) 25.52 27.53 26.44
Nitrate (NO₃-) 21.70 24.22 23.75
Water calculated 13.29 10.42 11.72
“Assuming that the chlorate in ‘Intravenous Compound (Loffler)’ is
present as potassium chlorate and the nitrate is present as sodium
nitrate, the figures obtained by the analysis correspond to a mixture
approximately as follows:
Potassium chlorate (KClO₃) 38.6 per cent.
Sodium nitrate (NaNO₃) 32.6 per cent.
Potassium borate (K₂B₄O₇) 4.9 per cent.
Sodium borate (Na₂B₄O₇) 4.0 per cent.
Boric acid 21.1 per cent.
“From the results of the examination it is concluded that this
preparation is a mixture of alkali chlorate and nitrate and boric
acid, probably produced by fusing together the constituents. It is
practically the same mixture as Oxychlorine and Zyme-oid as analyzed
nearly fourteen years ago in the A. M. A. Chemical Laboratory.”
Throughout the advertising of “Intravenous Compound (Loffler)” the
physician is reminded of the financial returns that the product offers.
“... The financial return will prove as interesting to yourself as
results are to the patients.”
“And lastly but not less interesting, the financial returns are
commensurate with results.”
“... the instruction given me in the use of your Intravenous
Compound and the opportunity presented adds four to five hundred
dollars per month to my bank account.”
“... will not only give you more positive results than have
ever obtained in chronic and progressive diseases but a very
remunerative business.”
“Intravenous Compound (Loffler) is supplied in granular form, 2
ounces to a bottle, at $2 per bottle. An ounce will average fifteen
treatments and treatments are at from $3 to $5 each, according to
the ability of the patient to pay.”
A physician whose name the Intravenous Chemical Company had given as
a user of Intravenous Compound (Loffler) was written to by another
physician who was interested in the matter and he was asked frankly for
his opinion. He replied in part:
“The treatment makes a profound impression on the recipient and is
usually followed by a marked improvement mentally, and I have not
been keen enough to draw the line of just how far the physical or
material improvement went and when the psychical began.
“For the office ‘specialist’ of the advertising type this would be
a boon, but I am not entirely satisfied that its use completely
justifies its claims.”
SUMMARY
Intravenous Compound (Loffler) stands revealed as a nostrum of secret
composition which physicians are asked to inject into the veins
of their patients. It must be purchased in connection with some
supplementary material, “a complete set of apparatus,” sold by the
same concern. Its successful administration is said to depend on
following a technic detailed either in a booklet sent out by Loffler
or given by Loffler in a “Post-graduate Course” which costs physicians
$50 unless they have purchased six dollars’ worth of another nostrum,
“Thymozene.”
The intravenous administration of drugs is impressive. To the patient
the technic is mysterious and its psychic effect striking. Its
dangers--infection, air embolism, intravascular clotting, sudden
death--are matters of record. Every conservative physician will admit
that there is no excuse for the intravenous administration of even
those drugs that are well known and whose effects have been carefully
studied, except when distinct advantages are to be secured. As The
Journal has stated before, “Little is known of the results to be
expected from intravenous therapy even with simple substances.”
What, then, can be said of the physician who subjects his patients to
the intravenous injection--“at from $3 to $5 each, according to the
ability of the patient to pay”--of a preparation of whose composition
he is as ignorant as he must be of its effects? Intravenous Compound
(Loffler) has been on the market ten years; it is unmentioned in the
literature of scientific medicine. The name of its exploiter, while
not unknown in the twilight zone of professionalism as the exploiter
of a nostrum, as a “Specialist” in “Chronic Troubles” and “Intravenous
Therapy,” as well as in other capacities even less savory, is equally
unknown to scientific medicine.--(_From The Journal A. M. A., Nov. 12,
1921._)
INTRAVENOUS SPECIALTIES
_To the Editor_:--There is a salesman here in Salt Lake City making
extravagant claims about the medicines advertised in the enclosed
pamphlet. Would you kindly advise me as to your opinion of it?
W. C. Schulte, M.D., Salt Lake City.
_To the Editor_:--I am interested in knowing the attitude of the
Council on Pharmacy and Chemistry regarding the products of the
Intravenous Products Company of America, 121 Madison Avenue, New
York City. If the Council has already reported, please refer me to
the appropriate number of _The Journal_. If it has not, please give
me any information available.
H. B. Gessner, M.D., New Orleans.
ANSWER.--The Intravenous Products Company of America has not
requested the Council on Pharmacy and Chemistry to examine any of its
intravenous specialties, nor have they been discussed in The Journal
or examined in the American Medical Association Chemical Laboratory.
The firm’s list of specialties bears a striking resemblance to those
of other “intravenous specialty” firms. Endoarsan, like Venarsen of
the Intravenous Products Company of Denver, is stated to contain a
cacodylate (dimethylarsenate) along with mercury and iodid. Venarsen
was reported on unfavorably by the Council (The Journal, May 22, 1915,
p. 1780), the inferior efficacy of sodium cacodylate was discussed
(The Journal, March 25, 1916, p. 978) and the worthlessness of sodium
cacodylate as a spirocheticide confirmed by H. N. Cole (The Journal,
Dec. 30, 1916, p. 2012), William G. Ward (The Journal, Feb. 3, 1917,
p. 390), and R. L. Sutton (The Journal, Feb. 17, 1917, p. 566).
Endosal, like Venosal of the Intravenous Products Company of Denver,
is said to contain salicylate and a colchicum preparation (the latter
is also said to contain iodids). Venosal was found unacceptable for
New and Nonofficial Remedies by the Council on Pharmacy and Chemistry.
Like other “intravenous” firms, this company advertises the intravenous
administration of drugs such as sodium iodid and hexamethylenamin. The
objections to and the dangers of indiscriminate administration of drugs
intravenously was recently emphasized in a report of the Council on
Pharmacy and Chemistry “Some of Loeser’s Intravenous Solutions” (The
Journal, April 16, 1921, p. 1120).--(_Query from The Journal A. M. A.,
Dec. 10, 1921._)
IODEX
At fairly frequent intervals physicians receive through the mail free
samples of “Iodex,” a black ointment sent out in small, circular
aluminum boxes. Iodex is sold by Menley and James, Ltd., New York City,
under the claim that it is a preparation of free iodin,[252] minus
the objectionable features that go with free iodin. The preparation
was examined in the A. M. A. Chemical Laboratory in 1915, and found
practically devoid of free iodin. The laboratory also reported that
when 1 or 2 grams of Iodex was rubbed on the skin of the forearm on
several subjects and the urine collected and tested for iodin, the
results were negative. This disproved the claim that “thirty minutes
after inunction [with Iodex] iodine can be found in the urine.”
[252] “Free” or elementary iodin (such as the tincture of iodin)
is used externally for its local irritant and antiseptic effects.
“Combined iodin” (_e. g._, iodid of potassium), does not produce
these effects; and when preparations containing iodin in combined
form are used, it is with the expectation of obtaining the systemic
(“alterative”) effects such as are produced by iodids.
The findings of the laboratory, which were summed up in a report (The
Journal, June 19, 1915) of the Council on Pharmacy and Chemistry on
Iodex, were essentially as follows:
1. The composition is incorrectly stated; the actual iodin content is
only about half of that claimed.
2. The action of Iodex is _not_ essentially that of free iodin,
although that is the impression conveyed by the advertising.
3. The assertion that iodin may be found in the urine shortly after
Iodex has been rubbed on the skin has been experimentally disproved.
At the time the laboratory reported its findings, it pointed out the
obvious contradiction in the claim that Iodex is not only an “effective
free iodine application without drawbacks” but also a means of “really
efficient external iodine therapy without stain or irritation.” It is
impossible to have free iodin present in sufficient quantities to be
therapeutically efficient and not get skin stains and irritation.
In a recent issue of the house organ, _Pharmacal Advance_, there
was a large display advertisement of Iodex under the heading: “For
prophylaxis and to ‘Double Cross’ Disease,” with the claims:
“Free Iodine.”
“Rub Through Skin.”
“Does Not Irritate nor Stain.”
On other pages of the same issue these claims appeared:
“There is no therapeutic virtue in Iodex which is not
inherent--though often latent--in Free Iodine; and there is no
virtue in Free Iodine which is not available in Iodex.”
“In Iodex all the beneficent properties of Iodine are emphasized
and all its disadvantages are eliminated--in a word, Iodex is
Pure Free Iodine presented therapeutically active and efficient,
ready for use in all conditions, with all the well-known powers
of Free Iodine, but without the sequelæ of unpleasant effects, as
irritation, corrosion, desquamation, staining, etc., which defeat
the ends of treatment when ordinary preparations of Iodine are
used. The fact that Free Iodine in the form of Iodex can now be
used in rectal and vaginal treatment, without irritation, speaks
volumes for its penetrability and bland action.”
These quotations are sufficient to show that the manufacturers of Iodex
still persist in their claim that the product contains free iodin.
In view of this, the A. M. A. Chemical Laboratory has again examined
Iodex, having recently purchased specimens on the open market. It
reports that Iodex gives no test for free iodin, or at most, but minute
traces.
An interesting side-light on the methods of Menley and James is also
brought out in the issue of _Pharmacal Advance_ just quoted. Under a
“department” misnamed “Book Reviews” the following appears:
“THE ACTIONS OF DRUGS.--Torald Sollmann, M.D. Published by W. B.
Saunders Co., Philadelphia. This is a book of lectures designed
for students in pharmacy and deals with the subject in plain and
simple language. The author in his introduction has brought out the
fact that over-counter prescribing is baneful both to the public
and to the pharmacist himself. Among some of the interesting points
brought out that _Pharmacol Advance_ has always maintained, namely,
that ‘Potassium iodid is not absorbed efficiently by the skin;
hence the ointment of potassium iodid is unscientific.’
“We would especially call attention to Ungt. Iodi U. S. P.,
containing Potassium Iodid, used as a solvent for its iodin
content. Accepting Sollmann’s statement, it is to be assumed that
Ungt. Iodi U. S. P. has not 100 per cent. efficiency.”
Garbling statements from scientific works for the purpose of puffing
proprietaries is not unusual in nostrum exploitation. The facts are
that the statement in Sollmann’s book, introduced in the Menley and
James house organ under the guise of a book review, appeared in a
discussion of iodin compounds. In this the author points out that
to obtain systemic iodid effects, it is irrational to apply iodin
preparations externally. So far as the free iodin content of the
official ointment of iodin is concerned, L. E. Warren (Reports of the
A. M. A. Chemical Laboratory, 1917) has shown that even after more
than six months this ointment still contains about 75 per cent. of the
free iodin originally added. The official ointment (Unguentum Iodi,
U. S. P.), therefore, so far as its free iodin content is concerned,
is far superior to Iodex, which contains no iodin in its free
state.--(_From The Journal A. M. A., May 3, 1919._)
THE WILLIAM F. KOCH CANCER REMEDY
A number of inquiries have been received of which those that follow are
typical. This from a Philadelphia physician:
“Would you give me any information you have about one so-called
‘Dr. W. S. Koch,’ Detroit, Michigan? This man is said to claim to
have in his possession a cure for cancer, the nature of which I do
not know. I know, however, that he obtained a very large fee not
very long ago in treating a case, but without success ...”
While a Chicago physician writes:
“I have at hand a pamphlet from Wm. F. Koch, M.D., Ph.D., of
Detroit, Mich., which is supposed to be a reprint from the _Medical
Record_ of Oct. 30, 1920, entitled ‘A New and Successful Diagnosis
and Treatment of Cancer.’ Will you kindly advise me what you know
about this man’s work on this subject and how much stock I can put
in the claims he makes in this article?”
And this from a physician in Seattle, received a few days ago:
“Has your office any knowledge of the cancer cure devised by Dr.
William F. Koch, Ph.D., M.D., of Detroit? He published an article
on it in the _Medical Record_, Oct. 30, 1920.... I enclose copy
of letter received by one of our patients from his ‘western
representative’ which reads like pure quackery. I do not find Dr.
Koch’s name in either the A. M. A. or Polk’s medical directories.”
The letter referred to in the last inquiry as coming from Dr. Koch’s
“western representative” was addressed to a woman who had written to
Dr. Koch with reference to his alleged cancer cure. The letter, dated
Jan. 19, 1921, was signed “Chas. L. Tisdale, 1898 Geary Street, San
Francisco.” It read:
“_Dear Madam_:--Your letter of January 10th written to Dr. Koch of
Detroit in reference to his cancer cure has been sent to me by Dr.
Koch. I am the western representative of Dr. Koch and am giving the
treatments with his remedy. I am now treating 14 cases here with
some most wonderful results. The amount of the remedy that Dr. Koch
can supply me with is limited and it is a very expensive substance.
None of it can be sent to Seattle or any other place for I have
only enough to treat the cases that are constantly presenting
themselves here. If you could come to San Francisco and have the
money to pay a reasonable fee, say enough to pay for the remedy, I
would be very glad to do everything I can for you.
“The results that have already shown in many of these cases warrant
me in believing that almost any case of cancer can be cured if the
treatment is persisted in.”
According to our records, Dr. William F. Koch of Detroit was born in
1885. Some years ago he graduated in chemistry and for some time held
the position of professor of physiology and physiologic chemistry at
the Detroit College of Medicine and Surgery. In 1918, Dr. Koch received
his degree in medicine from this same college. Less than a year after
his graduation, Dr. Koch declared that he had “developed a real
specific cure for cancer.” In the _Detroit Medical Journal_ for July,
1919, there appeared a brief article by William F. Koch, entitled “A
New and Successful Treatment and Diagnosis of Cancer.” A more extensive
article bearing the same title was published in the _New York Medical
Journal_ of Oct. 30, 1920.
As a result of the publicity that was given the Koch treatment, the
Wayne County (Detroit) Medical Society appointed a committee to
investigate the treatment. Its first report appeared in the Bulletin
of the society for Dec. 22, 1919. Briefly, this report said that the
Board of Health of Detroit had placed at the disposal of the committee
twelve beds in a local hospital with the necessary special nurses and
everything else required free of charge. The committee sent certain
patients to the hospital; and there were also some other patients
recommended by different physicians as proper cases for treatment.
There were nine altogether. After going over the cases carefully, the
committee found some in which the diagnosis was doubtful. There were
five cases, however, of undoubted cancer, a positive diagnosis having
been made from specimens and microscopic examination. The management
and treatment of these patients were turned over to Dr. Koch.
Dr. Koch seems to have raised certain objections and to have made
certain criticisms. He also insisted that he ought to have some
representative on the committee. The committee offered to put on any
and all he would name. He failed to name any. The committee reported
further that Dr. Koch was very negligent in his treatment of the
patients and finally, on November 26, the committee met with Koch and
went over all the cases with him. At that time he gave the patients
injections and promised to attend to the treatment regularly in the
future. According to the report, he saw the patients only once more
(three days later) and then did not come near them again. As the
patients became disgusted with the neglect, some of them left and
the committee sent the rest home and closed its connections with the
investigation of the subject.
In the same issue of the Bulletin of the county society in which this
committee’s report was published, the editor of the Bulletin stated
that from all sections of the country inquiries were coming relative to
the treatment and “from long distances patients are coming to Detroit
to be ‘cured’ of cancer.” The editor further stated: “It is reported
that Dr. Koch is treating many patients, promising much and charging
well.” To this Dr. Koch retorted that only about 30 per cent. of his
patients had “contributed.” The rest were treated free.
The Wayne County Medical Society Bulletin for Jan. 5, 1920, was
devoted almost exclusively to another discussion of Dr. Koch’s “cancer
cure.” It was there stated that a second committee had been appointed
to gather what information could be obtained from outside sources
relative to cases treated by Dr. Koch. This committee reported that
of fifty-six cases of which it was able to obtain data, only three of
the patients showed clinical improvement; twenty-one of the patients
were dead. Three more patients treated both by the Koch injections and
by operation were reported as clinically improved. The condition of
eighteen of the patients was reported as stationary, or unimproved. In
eleven of the cases, the results were unknown but the surgeons reported
unfavorably.
The committee reported further that Dr. Koch’s records were incomplete
and that he had submitted no proof that his injections have any
particular merit and the committee concluded that the study “is
entirely experimental and improperly supervised.”
Evidently, the most that can be said of Dr. Koch’s alleged “cure”
for cancer is that the claims made for it have not been supported by
independent investigators.--(_From The Journal A. M. A., Feb. 12,
1921._)
Further Comment
Last week some space was given to the alleged cure for cancer put out
by Dr. William F. Koch of Detroit. Incidentally, it should be mentioned
that Dr. Koch’s article of Oct. 30, 1920, to which reference was made,
appeared not in the _New York Medical Journal_, as stated, but in the
New York _Medical Record_.
The following correspondence throws additional light on the subject:
_To the Editor_:--To the number of inquiries which you have received
regarding the alleged cure of cancer by Dr. Koch, permit me to add
the following personal experience. On July 1, 1920, I was asked to
examine an ex-patient of mine whom I had not seen professionally for
many years. Her husband frankly told me that for several months his
wife had been treated by Dr. W. F. Koch for inoperable carcinoma of
the pelvic organs, that he wished Dr. Koch to retain charge of the
treatment but hoped I would give my opinion regarding certain nervous
manifestations in the patient which were causing him (her husband)
much concern.
At the same time, he showed me a letter written by Dr. Koch
purporting to explain the symptoms and offering suggestions regarding
treatment. I called on the patient and found her in the last stages
of generalized carcinomatosis. Simple palpation of the abdomen
revealed multiple nodules involving both lower and upper abdominal
quadrants. I did not feel justified in making a pelvic examination
but noted a profuse foul-smelling discharge on the vulvar pad. My
prognosis did not meet with the deluded husband’s approval. The
patient died within a week and a necropsy confirmed the clinical
picture of carcinomatosis. Enclosed is Dr. Koch’s letter; the
patient’s name should, of course, be omitted if you see fit to
publish this note.
George de Tarnowsky, M.D., Chicago.
The letter from Dr. Koch which Dr. de Tarnowsky enclosed with his own,
follows. We have, of course, deleted the name of the patient.
_Dear Doctor_: Mrs. ---- has absorbed and is still absorbing some
killed tumor tissue. She has absorbed some three pounds, I judge.
The results of the absorption are intoxication quite general
(nervous, muscular, perhaps nephritic). The myocardium at present
shows no signs of poisoning but the skeletal muscles and nerve
do. The important toxin liberated by the killed tissue is methyl
cyanimide which combines ammonia (NH₂) from the amino acids, and
thus becomes methyl guanidine. This latter has produced in my
patients an intoxication varying in similarity to: idiopathic
tetany in children, chorea in children, eclampsia in women, and
has even been so severe as tetanus in some of the muscle spasms; a
toxic albuminuria has resulted in some of my cases.
All of my cases have cleaned up so far. Of course, I cannot predict
in any individual case, except that when the absorption has been
completed and the toxin all eliminated, everything should return to
normal, unless the toxin has destroyed tissue beyond physiological
repair. My suggestions as to treatment would be elimination, saving
the kidneys as much as possible, by whatever methods you find best
and necessary.
At present I am treating symptomatically thus--atropin as a
guanidine antidote, arsenic as a chorea coupled antidote as a
prevention to the production of guanidine from the cyanimide, the
use of dilute hydrochloric acid has proven successful to me. Even
a urine boiling solid--albumen has cleared up in one case in three
days just by taking large quantities of 1/2 per cent HCl. I am
explaining the factors I have contended with in these cases, but
do not want to influence your plan of treatment when your judgment
finds me insufficient.
Sincerely,
Wm. F. Koch.
I shall have a publication out very soon on the treatment of these
tetanics and eclampsia with HCl.
It is worth noting that this letter of Dr. Koch’s was written June 28,
just three days before Dr. de Tarnowsky saw Mrs. ---- and less than a
week before she died of generalized carcinoma.
Not the least important element in the story which these two letters
tell is the optimism engendered in the husband of the poor cancer
patient by the widely vaunted treatment of Koch. And herein lies one
of the most pernicious features connected with the exploitation of
alleged cures for cancer, tuberculosis, etc. All such remedies, whether
fraudulent both in their inception and exploitation or those which
while equally worthless are at least honestly put forward and are based
on a certain amount of scientific investigation, produce a profound
and marked temporary change in the patient’s condition. It is this
that tends to warp the judgment not only of the unscientific layman,
but also of the physician. The psychic element in cancer has been well
described by Weil:
“It is, indeed, very remarkable that a patient who has been consigned
to death as a victim of a hopeless malady, should regain his spirits
and his appetite, when he is again confronted with the hope of a
cure, and of the eradication of his disease? It is a phenomenon
well known to every student of the disease that a large proportion
of cases responds in just this manner to any treatment which is
offered them. Osler has described a case of cancer of the stomach
in which the mere visit to a consultant of sanguine temperament,
though poor judgment, whose assurance of the patient that there
was no possibility of cancer, resulted in the disappearance of all
the symptoms and a gain of 18 pounds in weight. It is this psychic
influence, which has occasionally deluded the honest student of
cancer cure, and which has also so generously played into the hands
of the dishonest.”--(_From The Journal A. M. A., Feb. 19, 1921._)
THE LUCAS LABORATORIES’ PRODUCTS
The Journal has received several inquiries about the products put out
by the Lucas Laboratories, Incorporated, of New York City. A typical
inquiry is that received from Dr. F. A. Jewett of Brooklyn, who writes:
“The enclosed circular is sent out to the medical profession by Dr.
William Lucas, 287 W. 70th St., New York. What do you know of this
man and his methods?”
William H. Lucas was graduated by the Medical College of Ohio in 1895
and was licensed in 1897. He is not a member of his local medical
society. The products put out by the Lucas Laboratories are for
intravenous use, and their method of exploitation indicates that the
concern is less interested in the science of therapeutics than it is
in taking commercial advantage of the present fad for intravenous
medication. The Journal has protested editorially against the
unnecessary use of the intravenous administration of drugs, and the
abuse of this method of drug giving prompted the Council on Pharmacy
and Chemistry recently to emphasize the danger of indiscriminate
intravenous medication.
The products of the Lucas Laboratories, Inc., have not been examined
either by the A. M. A. Chemical Laboratory or by the Council on
Pharmacy and Chemistry. The composition of these products is
essentially secret, which in itself should be sufficient to deter
physicians from using them. Of course, in accordance with all the
tenents of orthodox nostrum exploitation, “formulas” are furnished.
Even the crude hieroglyphics that used to be palmed off on the
medical profession by nostrum exploiters under the guise of “graphic
formulas” are outdone by the Lucas Laboratories in publishing the
alleged formulas of its preparations. If we, as physicians, knew
more chemistry, the Lucas Laboratories would not find it profitable
to publish such ineffable nonsense as that which characterizes their
“literature.” For instance:
“‘Luvein’ Arsans (Plain)” is said to be: “Di hypo sodio calcio
phosphite hydroxy arseno mercuric iodid.” The first part of this
“formula” might stand for sodium and calcium hypophosphite. The
remainder is meaningless except that it suggests (but does not
insure) the presence of arsenic and mercury iodide.
“‘Luvein’ Arsans, Nos. 1, 2 and 3.”--“Meta hydroxy iodide sodio
arsano mercuric dimethyl benzo sodio arsenate, ai oxy sodio tartaria
sulpho disheuyl hydrazin.” Who can venture even a conjecture as to
the possible significance of this?
“‘Luvein’ Creosophite.”--“Ammonio hydroxy calcio sodio hypo-phosphite
arsenous pentoxy iodide.” While the name suggests creosote, the
“formula” gives no hint of this. It might refer to hypophosphites of
ammonium, calcium and sodium with iodide of arsenic. Whether arsenous
(trivalent arsenic) or arsenic (pentavalent arsenic) iodide or both
are intended, is a question.
“‘Luvein’ Hexacol.”--“Hexa methylenepyro catechin mono methyl amino
ether glycerite.” By moving these syllables around like the old
“fifteen puzzle” they can be arranged to represent hexamethylenamin
and monomethyl-ether of pyrocatechin, or guaiacol, having the
“glycerite” left over.
It is futile to discuss the therapeutic claims made for the various
preparations put out by the Lucas Laboratories. One might as profitably
discuss the therapeutic claims made for “Peruna” or “Paine’s Celery
Compound” for the exploitation of the latter products is on just as
high a scientific plane as the exploitation of the “Luvein” nostrums.
The proposition offered to physicians by the Lucas Laboratories, Inc.,
is an insult to the intelligence of the medical profession. Not that
the products themselves are necessarily any worse or any better than
many offered for intravenous use; the selling methods are more crude,
that is all.
The facts are, we have entered a new cycle of nostrum development. The
unscientific mixtures for oral administration that characterized so
large and disreputable a part of the proprietary medicine business of
the past two or three decades are giving way to equally unscientific
mixtures for intravenous use. The dangers of the older nostrums
are accentuated in the newer by the added element of risk that is
inseparable from intravenous therapy. Add to this the temptation to
the physician in the way of more substantial fees which, legitimately
enough, may be charged when intravenous administration is called for,
and the menace of the new style nostrum becomes evident. The Journal
can only reiterate the warning that intravenous therapy should be
employed only when most positively indicated. Further, because of the
danger that is inseparable from this method of drug administration,
physicians should be doubly careful to see that products employed
for intravenous use come from firms of unquestioned scientific
standing.--(_From The Journal A. M. A., Sept. 20, 1919._)
“PHYLACOGENS”[L]
[L] This matter was largely reprinted in the Propaganda for Reform,
eighth and ninth editions.
A physician in Florida writes:
“I am enclosing a copy of a circular letter just received from
Parke, Davis & Company, and will call your attention to a marked
paragraph in this letter on which I would like to have an
expression of your opinion.”
The circular letter which the doctor forwards is devoted to singing
the praises of “Pneumonia Phylacogen.” It opens with the statement:
“Influenza, we learn, has appeared in your section.” The paragraph
marked by our correspondent reads:
“Pneumonia Phylacogen has been found to be a dependable means of
preventing and treating pneumonic complications of Influenza. In
one large city it became a routine measure to give all persons
affected with Influenza an injection of Pneumonia Phylacogen as a
prophylactic of pneumonia. The results were remarkable. Not only
did the cases improve rapidly, but in a great majority of them the
pneumonia did not occur.”
The “Phylacogens” were repeatedly discussed in The Journal during 1913
and 1914 when these products were being pushed with much vigor by the
manufacturers. We know of no evidence that calls for a revision of
the statements then made regarding them. The injection of phylacogens
is simply the administration of a mixture of the filtered products
of several bacterial species. The results which follow represent the
reaction of the bacterial protein--a reaction for good or evil. There
is no scientific evidence to show that they possess any specific
prophylactic virtue. To recommend their use in cases of influenza,
as a prophylactic against pneumonia, is unwarranted, and the
physician who acts on the advice of the manufacturer must assume the
responsibility for the results. In case of mishap he cannot fall back
on the manufacturer; he will find no scientific evidence to support
him.--(_From The Journal A. M. A., Nov. 15, 1919._)
PINEOLEUM ADVERTISING METHODS
Capitalizing the Name and Position of the President of the
American Medical Association
_To the Editor_:--Enclosed is a postal card which a physician in
Oklahoma has sent me together with thirty-six cents in stamps. The
envelop was addressed to me at the address of the Pineoleum Company.
The postoffice corrected the address and sent it to me. It is evident,
therefore, that the physician in Oklahoma thought I was sending these
postals as an employee of the Pineoleum Company, or, at least, was
endorsing their products.
[Illustration:
+---------------------------------------------------------------------+
| _TREATMENT OF INFLUENZA_ 408-10-12 West 13th Street |
| By A. LAMBERT, M. D., New York. Pres. A. M. A. New York City |
| |
| Dear Doctor: |
| |
| “The ‘Flu’ is coming back in October to scourge the whole world. |
| I expect the plague to come back as soon as people begin to live |
| indoors again. The death toll Will be serious, but I do not |
| expect it will be as bad as it was last winter.” |
| |
| --Dr. Royal S. Copeland, _Chief of the New York Health Department_. |
| |
| “The persistent spraying of the nose and pharynx with some form of |
| silver salt, or some form of mild disinfectant, materially aids in |
| confining the infection in its early stages to the upper passages, |
| and this procedure gives the impression, when tried in a large |
| number of patients, that it prevents in many cases the spread down- |
| ward into the bronchi and thus limits pulmonary complications.” |
| --Extract from “The Treatment of Influenza,” by A. Lambert, M.D., |
| in the Journal of the American Medical Association, August 2nd, |
| 1919. |
| |
| =We have letters from a large number of physicians confirming the |
| above extract, and with the further statement that as a _preventive_|
| and _relieving_ agent there is no combination before the profession |
| today so satisfactory as Pineoleum.= |
| |
| =If you have not received recently, a complimentary Outfit, return |
| this card with 36 cents in stamps and we will forward a regular |
| $1.00 package by prepaid Parcels Post.= |
| |
| _THE PINEOLEUM COMPANY_ |
+---------------------------------------------------------------------+
Postal card capitalizing the name and position of the President of
the American Medical Association.]
Kindly do me the favor to publish this letter in The Journal as a
protest against the dishonesty of this method of advertising. What is
quoted from an article that I wrote appeared originally in the _New
York State Journal of Medicine_ and was abstracted in The Journal
of the American Medical Association of August 2, 1919. The obvious
inference to be drawn from this postal is that I referred to the
products of the Pineoleum Company in that article. I did not have the
products of the Pineoleum Company in my mind. I never have used their
products and never prescribed them.
This form of advertising is done with intent to deceive and did deceive
the doctor in Oklahoma. It was therefore a successful falsehood, its
success depending on the false use of the name of the President of the
American Medical Association to bolster up the sale of the product.
I resent the use of my name in connection with the quack advertising
of nostrum venders. The low, vulpine cunning of the method used is
on the same level as the deceit and dishonesty which use this form
of advertising to the injury of my name and reputation. As President
of the American Medical Association I must insist that you protect
me by publishing this letter in The Journal, giving it as widespread
publicity as possible.
Alexander Lambert.
[Comment.--“Pineoleum” is a “patent medicine” advertised in the
cheapest and most effective way--by the aid of the easy going and
complacent physician. In 1906 Pineoleum was being marketed by the
Winslow Laboratory of New York City, which also put out three or four
other nostrums--“Morumalt,” “Egeriol,” “Digestylin,” and “Ford’s
Nucleo-Peptone.” Pineoleum was advertised to the public then as it is
advertised now, via the medical profession. Physicians are circularized
and are offered a petty graft in the form of a cheap nebulizer and a
sample bottle of Pineoleum. Some time ago the company seems to have
developed a scheme whereby physicians could make money “dispensing
Pineoleum nebulizer outfits at more than 140 per cent. profit.” The
Pineoleum concern for years has also polluted the stream at its source
by attempting to get the secretary of the senior class of every medical
school to distribute its free nebulizer outfits to members of the
class and receive therefor 5 cents for each outfit distributed! The
life history of Pineoleum is that of the typical nostrum. Epidemics,
of course, are utilized as opportunities for pushing the product. In
1911 a card was sent out featuring “A Special LaGrippe Offer”; in 1916
the profession was circularized recommending Pineoleum as “The Ideal
Prophylactic” in infantile paralysis; during the past year influenza
has again been the selling point.
The case described by Dr. Lambert is not the first example of the
misuse of names and statements of physicians. Last December the
Pineoleum concern was sending out an advertising card in which Dr.
McCoy of the United States Public Health Service was quoted as
recommending Pineoleum as the “bulwark of prevention” and “battery of
relief” in influenza. Of course, Dr. McCoy never said anything of the
sort. A protest against this particular falsehood resulted in another
card being sent out several months later by the Pineoleum people
purporting to explain and apologize for the misquotations and putting
the blame on the printer. The “apology” ended with a postscript (in
larger and bolder face type than the body of the card) that urged
physicians to “secure our liberal introductory advertising proposition
on improved oil nebulizer outfits.” From the standpoint of publicity
for Pineoleum, the “explanation and apology” was doubtless as good an
advertisement as the original card of misrepresentation.--Ed.]--(_From
The Journal A. M. A., Nov. 1, 1919._)
“PROTEAL THERAPY” AND HENRY SMITH WILLIAMS
_To the Editor_:--Will you please advise as to the success and
safeness in using the Proteal treatment for tuberculosis by Henry
Smith Williams, M.D., LL.D., 104 East 40th Street, New York?
C. P. Burchard, Alamogordo, N. M.
_To the Editor_:--Kindly send me any available information on
“The Proteal Treatment for Cancer.” An article by Dr. Henry Smith
Williams, 120 West 32 Street, New York City, in April _Hearst’s_
has caused relatives to request its use in a case of carcinoma of
the liver under my care.
M. M. Reppard, Middlebourne, W. Va.
_To the Editor_:--I am enclosing a leaflet, mailed to me on
request, by Dr. Henry Smith Williams of New York City, who
published a series of articles during the last year in _Hearst’s
Magazine_ on “Proteal Therapy.” If you have investigated this man
and his proteal treatment, I should like to know the result of
your findings. I am a consumptive and am, therefore, particularly
interested in its alleged benefactions for the treatment of
tuberculosis.
Michael A. Long, Glen Lake Sanitarium, Hopkins, Minn.
_To the Editor_:--What information can you give me regarding Henry
Smith Williams, M.D., LL.D., 104 East Fortieth Street, New York,
and the therapeutic value of the “Proteal Therapy” that he has
originated?
M. D. Baker, M.D., San Jose, Calif.
The above letters are selected from many received on the subject.
Henry Smith Williams is better known in the journalistic world than
in the field of scientific medicine. He was graduated by the Chicago
Medical College in 1884. In the thirteen issues of medical directories
of the United States that have been published during the past thirty
years Dr. Williams’ name does not appear--except for the issues of
1890 and 1893--until the 1914 edition. So far as we have been able
to find, Dr. Williams had not until 1915 contributed any articles to
medical journals. The catalog of the Surgeon General’s Library contains
no reference to any articles of Dr. Williams except those that have
appeared in popular magazines. The volumes of the Index Medicus from
1907 until 1914, inclusive, also contain no references to any articles
by him in medical journals. The Journal‘s author index to current
medical literature from 1900 to 1914, inclusive, fails to record any
articles by Dr. Williams in medical journals. Dr. Williams’ articles,
however, in popular magazines have been voluminous and numerous.
Sometimes his articles have been under his own name and sometimes
under the nom de plume, “Stoddard Goodhue, M.D.” Under the latter name
the _Cosmopolitan_ published articles on “Adding Years to Your Life,”
“Battle of the Microbes,” “Do You Choose Your Children?” and “What is
the Matter With Your Brain?” Under his own name articles have appeared
in popular magazines on such subjects as “Burbank’s Way with Flowers,”
“Every Woman Her Own Burbank,” “Why Not Live Forever?” “Science of
Breeding Kings,” “New Cancer Treatment” and “New Hope for Rheumatism
Sufferers.” In addition, Dr. Williams has published books on such
subjects as “History of the Art of Writing,” “Historians’ History of
the World,” “Story of Nineteenth Century Science,” “Luther Burbank,”
“Twilight Sleep” and others. The Goodhue Company of New York City,
which publishes some of Dr. Williams’ books has, we understand, for
its president, Dr. Henry Smith Williams, for its vice president, Dr.
Williams’ wife, and for its secretary-treasurer, Dr. Williams’ daughter.
Readers of The Journal will remember the publicity given in 1915
and 1916 to an alleged treatment for cancer, sometimes called the
“Horowitz-Beebe Autolysin Treatment.” The method was heralded widely
both in a certain portion of the medical press and in popular magazines
and newspapers. A popular article by Henry Smith Williams on “The New
Cancer Treatment” appeared in the _Illustrated World_ for October,
1915, with pictures of Dr. Horowitz, Dr. Beebe, etc. A month or two
later, physicians received, gratis, from the Goodhue Company a neatly
bound little book on “Alcohol Hygiene and Legislation,” by E. H.
Williams, M.D. (brother of Henry Smith Williams). Enclosed with it
was a letter from the Goodhue Company asking physicians to accept the
book. The body of the letter was devoted to calling the attention of
physicians to an “important work” by Dr. Henry Smith Williams on “The
Autolysin Treatment of Cancer” that the Goodhue Company was publishing.
With the letter, there was a small advertising pamphlet “Issued by
the Autolysin Laboratory” and advertising that product. In addition,
the last thirteen pages of the book on “Alcohol Hygiene” contained
advertisements of the Goodhue Company’s publications with particular
emphasis (four pages of it) on the “Autolysin Treatment of Cancer,” by
Henry Smith Williams.
In May, 1917, physicians in the West received a letter from the
“Ellison-White Chautauqua System” informing them that Dr. Henry Smith
Williams was to lecture at “your Chautauqua” and reminding them that
“he has recently issued two volumes, ‘The Autolysin Treatment of
Cancer’ which he believes will be his greatest contribution to medical
science.” The present “Proteal” treatment appears to be a modification
of the “Autolysin” treatment. Dr. Williams, in attempting to justify
the use of his “Proteal” in tuberculosis, cancer, rheumatism, etc.,
takes advantage of certain investigations bearing on the nonspecific
reactions resulting from the parental injection of foreign proteins.
So far as we can discover, there is no scientific evidence to indicate
that the “Proteal” treatment expounded by Williams is of value in the
treatment of cancer, tuberculosis or the other numerous diseases for
which the “Proteals” are recommended.
It is a question whether such articles as those on “The Proteal
Treatment of Cancer,” “New Hope for Rheumatism Sufferers,” etc.,
published in popular magazines or newspapers serve any useful public
purpose. May they not, on the contrary, by raising false hopes, cause
much mental suffering and do scientific medicine great harm?--(_From
The Journal A. M. A., July 6, 1918._)
PROTEOGENS
Commercial Therapeutics[M]
[M] See index for additional articles on proteogens.
A report of the Council on Pharmacy and Chemistry that appears
elsewhere[253] in this book deals with another attempt to foist on
our profession a series of essentially secret preparations whose
therapeutic value has not been scientifically demonstrated. Grotesquely
extravagant claims are advanced as to the therapeutic potency and
range of action of substances of whose nature and effects we have
no trustworthy information. Physicians are advised to use--and many
undoubtedly are using--these alleged remedies in the treatment of
diseases in which delay in the proper kind of treatment may be of
the greatest danger to the patient. As stated, there is available
no reliable information regarding the effects of these substances
when they are introduced in the human body. They may have no effect
whatever, or they may produce more or less direct injury; in either
case, there is the chance that damage, even irreparable to the patient,
may result because rational treatment is withheld.
[253] Page 227.
If we accept the statement that the preparations are largely vegetable
proteins, it is a fair inference that, under certain conditions,
they may cause a febrile reaction of the same general nature as that
caused by other foreign proteins when injected into the body. We know
that such reactions are not without danger and that the treatment of
certain infections by induced reactions to foreign proteins is strictly
an experimental procedure to be undertaken only under very special
conditions. There is, therefore, no known valid reason why a physician
should assume the responsibility for using these alleged remedies in
the treatment of his patients; there is a very obvious reason why he
should not--the therapeutic instructions of “the House of Merrell,
always interested in the progress of plant therapy” to the contrary
notwithstanding. It is the old story of exploiting physicians through
commercial pseudoscience; of trading on the credulity of the profession
to the detriment of the public. As Osler[254] recently protested so
vigorously:
[254] Advance pages, the Oxford Medicine, 1919, Vol. 1, Part. 3, p. 245.
Some time ago a pamphlet came from X and Company, characterized by
brazen therapeutic impudence, and indicating a supreme indifference
to anything that could be called intelligence on the part of the
recipients. That these firms [manufacturing pharmacists] have the
audacity to issue such trash indicates the state of thraldom in
which they regard us. And I would protest against the usurpation
on the part of these men of our function as teachers. Why, for
example, should Y and Company write as if they were directors of
large genito-urinary clinics instead of manufacturing pharmacists?
It is none of their business what is the best treatment for
gonorrhea--by what possibility could they ever know it, and
why should their literature pretend to the combined wisdom of
Neisser and Guyon? What right have Z and Company to send on a
card directions for the treatment of anemia and dyspepsia, about
which subjects they know as much as an unborn babe, and, if they
stick to their legitimate business, about the same opportunity of
getting information? For years the profession has been exploited
in this way, until the evil has become unbearable, and we need as
active a crusade against the pseudoscience in the profession as
has been waged of late against the use of quack medicines by the
public. We have been altogether too submissive, and have gradually
allowed those who should be our willing helpers to dictate terms
and to play the rôle of masters. FAR TOO LARGE A SECTION OF THE
TREATMENT OF DISEASE IS TODAY CONTROLLED BY THE BIG MANUFACTURING
PHARMACISTS, WHO HAVE ENSLAVED US IN A PLAUSIBLE PSEUDOSCIENCE.
What shall the profession do to protect itself against this
humiliation--to throw off the credulity that extols pseudoscience and
makes commercialized empiricism financially profitable? Osler says
the remedy is obvious: “Give our students a firsthand acquaintance
with disease, and give them a thorough practical knowledge of the
great drugs, and we will send out independent, clear-headed, cautious
practitioners who will do their own thinking and be no longer at
the mercy of the meretricious literature, which has sapped our
independence.” Excellent! But must humanity wait a generation? Why not
stop this evil at once? The American Medical Association has provided
the means whereby this can be done, if physicians will only make use
of it--the Council on Pharmacy and Chemistry.--(_Editorial from The
Journal A. M. A., July 12, 1919._)
An Alleged Endorsement of Proteogens Repudiated
_To the Editor_:--I note in the issue of The Journal for July 12, a
statement regarding the so-called “Proteogens” manufactured by the Wm.
S. Merrell Company of Cincinnati.
My attention has been called to the fact that salesmen of this company
have been exhibiting a letter purporting to show that this department
has endorsed their products in the treatment of venereal diseases.
The letter in question was written by a physician employed in one of
the clinics conducted jointly by this department and the U. S. Public
Health Service, and the stationery of the department was used without
authority. The physician in question has made numerous efforts to
recall the letter, but the Merrell people profess an inability to
control its use.
I need not add that this department has not endorsed and will not
endorse these products, and has no evidence that they are of any value
whatsoever.
Allen W. Freeman, M.D., Commissioner of Health,
State of Ohio, State Department of Health.
--(_Correspondence in The Journal A. M. A., July 26, 1919._)
The Manufacturer’s Protest and a Reply
_To the Editor_:--Allow us to direct your attention to several
misstatements which appear in the letter signed, “Allen W. Freeman,
M.D., Commissioner of Health, State of Ohio,” published in The Journal
of the American Medical Association for July 26.
1. Salesmen of this company have _not_ been exhibiting a “letter
purporting to show that this department has endorsed their products in
the treatment of venereal diseases,” as stated by Dr. Freeman.
2. The author of the letter has _not_ “made numerous efforts to recall
the letter, but the Merrell people profess an inability to control its
use,” as stated by Dr. Freeman.
A physician employed in one of the clinics used our Proteogens Nos. 10
and 11 extensively and is still using them to a large extent in his
private practice. He is a man of standing in the community in which
he practices and is also a professor in one of the leading medical
colleges in the state.
The letter in question cites the case of a man who had been under
treatment for three years with 606, 914 and most of the other
treatments in general use, and on August 31, a year ago, still gave
a Wassermann test plus 4. He was given Proteogen No. 10, and by
the middle of December the Wassermann was negative and the man was
discharged as cured.
While this letter was written on the stationery of the Bureau of
Venereal Diseases of the Department of Health, State of Ohio, it was
written in the first person, and made no pretension in any way to being
official nor was any such pretense made or authorized by the Merrell
Company.
The author of the letter has _not_ made “numerous efforts to recall the
letter,” nor has the Merrell Company “professed an inability to control
its use.”
The physician did ask that the letter be returned to him, and his
request was complied with promptly.
[Then follows the full text of the letter in question. As its contents
have no bearing on the question under discussion, it is omitted.--Ed.]
In over ninety-one years of honorable service as manufacturers of
medicinal preparations, the Wm. S. Merrell Company has never endeavored
to advance its interests through misrepresentation.
The Wm. S. Merrell Company,
Chas. G. Merrell, Pres.
[The letter above was submitted to Dr. Allen W. Freeman, Commissioner
of Health of the State of Ohio. Dr. Freeman’s comments appear
below.--Ed.]
_To the Editor_:--The plain issue of veracity raised in the
communication of the Merrell Company must be settled on the evidence,
which is unfortunately too voluminous to be published in full in The
Journal. Copies of the correspondence in the case have been furnished
the editor, and the originals are on file in the office of the state
department of health in Columbus.
1. Whether or not the photographic reproduction of a letter written on
the letter head of this department, and the distribution of copies to
salesmen for display to physicians, was a conscious effort on the part
of the firm in question to create the impression that the letter was
an official one is perhaps a matter of inference. That it did create
such an impression is evidenced by the letters of inquiry received from
physicians who saw it.
2. The statement that the Merrell Company refused to return the
_letter_ is perhaps erroneous. They did apparently return the original
letter but not the _photographic copies_ which had been distributed to
their salesmen. On May 22 the firm wrote as follows:
“A number of physicians who are in cooperation with both state
and national bureaus of venereal diseases have been using our
Proteogens with marked success and there are doubtless many letters
carried by our salesmen--reports from some of these physicians.”
This was interpreted to mean that the firm had no method of knowing
what letters were carried by their salesmen and was not responsible for
them. Whether or not this interpretation is correct is again, perhaps,
a matter of opinion.
The purpose of the original communication was to make plain to those
of the profession who have already seen or might subsequently see the
letter referred to that the communication was the expression of an
individual and not of the Department.
A. W. Freeman, Commissioner.
--(_Correspondence in The Journal A. M. A., Sept. 6, 1919._)
Details of the Alleged Endorsement of Proteogens
Our readers will remember the recent correspondence published in The
Journal of July 26 and September 6, by Dr. A. W. Freeman, Commissioner
of Health of the State of Ohio and the Wm. S. Merrell Co. The letters
dealt with the use that had been made by the Wm. S. Merrell Co. of a
letter, written on the official stationery of the Bureau of Venereal
Diseases of the State Department of Health of Ohio, puffing one of the
company’s proprietary remedies--Proteogen No. 10.
Dr. Freeman wrote to The Journal calling the attention of the
profession to the use of this letter and explaining that the letter
was merely the expression of opinion of an individual, and not an
expression from the State Department of Health. The Wm. S. Merrell Co.
took exception to certain inferences made in Dr. Freeman’s letter and
in the course of a letter to The Journal regarding this, incorporated
the contents of the testimonial letter. The Journal, in publishing
the Merrell letter, omitted this testimonial on the ground that
the _contents_ of the letter had no bearing on the question under
discussion.
We have now received a letter from the company protesting against this
omission. The Journal, therefore, takes this opportunity of briefly
restating such facts as it has been able to get regarding the entire
matter and publishing the letter. The facts are as follows:
1. In February of this year a Cincinnati physician, Dr. C. J. Broeman,
wrote to Dr. A. S. Horovitz relative to alleged results with Proteogen
No. 10. The letter was written--without authority--on the official
stationery of the Bureau of Venereal Diseases of the State Department
of Health of Ohio.
2. The Wm. S. Merrell Co. had linen mounted photographs made of Dr.
Broeman’s letter and distributed them to their Proteogen detail men.
Accompanying these photographic copies was a communication to these
detail men describing the photographed letter as one written by:
“... a Cincinnati physician who is now Acting Assistant Surgeon,
U. S. Public Health Service, cooperating with the Bureau of
Venereal Diseases of the Department of Health of the State of Ohio.”
3. The right hand top corner of the official stationery, as can be
seen by the reproduction, bore the name of “James D. Bauman, Deputy
Commissioner.” Dr. Broeman’s signature was rather illegible and could
easily be mistaken, by those not knowing the handwriting of either
man, for the signature of Deputy Commissioner Bauman. In at least one
instance it was so mistaken, and the physician who was misled wrote to
the Director of the Bureau asking whether the testimonial for Proteogen
No. 10 which had been shown him by the Merrell detail man was really an
official communication.
4. On May 15, 1919, Commissioner of Health Freeman wrote to the
Merrell Co. stating that he had been informed that one of the Merrell
representatives was using as an advertisement a letter bearing the
letterhead of the Bureau of Venereal Diseases of the State Department
of Health and what purported to be a report signed by “Mr. Bauman,
Deputy Commissioner.”
5. On May 19, the Wm. S. Merrell Co. wrote Dr. Freeman that he was
certainly mistaken in regard to the use of any “report signed by
Mr. Bauman.” Dr. Freeman then sent to the company the letter he had
received from the physician who had mistaken Broeman’s letter for an
official letter by Bauman. Although it would seem that this letter
and Commissioner Freeman’s protest should have made plain to the Wm.
S. Merrell Co., the fact that the letter, incorrectly referred to
as Mr. Bauman’s, was in reality Dr. Broeman’s, the company remained
silent regarding its use of the Broeman letter and, on May 22, merely
reiterated that there had been “no letter circulated by this company
containing a testimonial of your Mr. Bauman.” On May 28 (six days
later) the Merrell company sent to its Proteogen detail men another
general letter, “for personal use of agents,” in which it again called
their attention to the “photographic copy mounted on linen” of Dr.
Broeman’s letter. This communication to the detail men also declared
that it “has been suggested that the further use of Dr. Broeman’s
letter might antagonize the State Department of Health” and, therefore
the detail men were told to “discontinue using the photographic copy in
question” and to return the photographs to the head office.
[Illustration: Reproduction (reduced) of one of the photographic
copies sent out by the Wm. S. Merrell Co. to its Proteogen detail men
to be shown to physicians. While the letter is a private one, it was
written (without authority) on official stationery. Some physicians
were misled into thinking it was an official endorsement of Proteogens.
The Merrell concern denied any intention to mislead and claimed that
it was interested only in bringing to the attention of physicians the
_contents_ of the letter!]
Here, briefly are the bald facts in the case. The essential point at
issue is whether these photographic copies of Dr. Broeman’s letter
would or would not be likely--whether or not they were so intended--to
mislead physicians into believing that the endorsement was an official
one by the State Board of Health rather than an individual one. One can
but wonder why, if, as the Merrell company so vehemently asserts, there
was no intention of misleading physicians on this point, the company
should have gone to the trouble and expense of _photographing_ the
entire letter, including the letterhead, rather than making typewritten
or mimeographed copies of the _contents_ of the letter.--(_From The
Journal A. M. A., Sept. 27, 1919._)
Dr. Broeman’s Final Report on Proteogens
_To the Editor_:--In the September 27 issue of The Journal my name
was mentioned in connection with the Merrell Chemical Company’s
“Proteogens” in the treatment of syphilis. The Merrell Chemical Company
promised not to use my name at any time in connection with their
“Proteogens” injection and they know that the use of my name has been
distinctly against my wishes. I feel that in justice to myself, as well
as the public, I should report the result of my experiments with their
“Proteogens” in private practice.
In explanation I might say that I began the use of their “Proteogens”
in April, 1918, and I feel that I now have enough data to give a
complete report. I might say that all my results have been practically
nil; particularly is this true in my cases of syphilis, which all had
a four plus Wassermann reaction when I discontinued using this form of
treatment.
Very truly yours,
C. J. Broeman, M.D., Cincinnati.
--(_Correspondence in The Journal A. M. A., Oct. 11, 1919._)
PULVANE
In a twelve-page pamphlet, sent out by the Pulvane Laboratories, Inc.,
of Des Moines, Iowa, and purporting to deal with “The Therapy of
Pulvane, an advanced method for the treatment of Respiratory Diseases,”
we are told that Pulvane “was developed in a United States Army General
Hospital by officers of the Medical Department.”
Pulvane “originally was intended only for its germicidal action
upon tubercle bacilli in the lung,” but it is now also recommended
for asthma, hay fever, bronchitis, rhinitis, laryngitis and “other
affections of the air passages.” Of the alleged action of Pulvane on
tuberculosis we read:
“It destroys the spores of the bacilli as well as the germs
themselves. It prevents infection of new areas by aspiration,
gravity or surface contact.
“In cases where sputum is positive it is a very noteworthy fact
that shortly after treatment is begun, the bacilli begin to
disappear, gradually diminish in number, and finally the sputum
becomes negative.”
Pulvane is administered, by inhalation, at the offices of the Pulvane
Laboratories, Inc. Its “discoverer” chanced on a method of “introducing
into solution and volatizing a certain germicide, extremely rare in
its usage because of its resistance heretofore to attempts to bend it
to scientific will.” This “rare” medicament is alpha naphthol! But
since the discovery of this volatizing method “three other ingredients
of high therapeutic value have been added.” What are these other
ingredients?
“They would be named were it not that Pulvane requires special
technique in its preparation and administration. Our medical
directors do not consider it advisable to identify them here
because of the possibility of incompetent hands attempting their
use. The medical directors, however, will be glad to name every
ingredient of Pulvane for any reputable member of the profession.
Pulvane Laboratories reserve only the method of compounding.”
Presumably, therefore, if physicians desire to know what Pulvane is,
the Pulvane Laboratories, Inc., “will be glad to name every ingredient
of Pulvane.” It is worth noting that nothing is said about quantities.
It is also worth remembering that “Peruna” and some other “patient
medicines” have for years printed on the label the _names_ of the
alleged ingredients. How much longer is the medical profession going to
be fooled with the trick of nostrum exploiters pretending a frankness
that means nothing?
From a recent issue of a Des Moines newspaper we learn that the Pulvane
Laboratories are about to establish a sanatorium where the Pulvane
treatment can be given. This announcement is said to be made by John P.
Mosher, the alleged discoverer of Pulvane. Mosher is not a physician.
The newspaper article states, further, that Mosher’s experiments were
tried out “under the observation of Major Sharpe,” commander at Fort
Des Moines. It appears also that an ex-newspaper reporter is connected
with the Pulvane Laboratories. The value of having a good publicity
man is obviously recognized. There also seems to be connected with the
concern a Dr. Harry P. Hall. We find in the records reference to one
Harry P. Hall who was graduated by the Medical Department of Drake
University of Des Moines, Iowa, in 1894, and was licensed in Iowa in
1896. Our records indicate that he has not been in practice for some
years. We also find in our files some newspaper clippings regarding a
Dr. Harry P. Hall who, in 1914, pleaded guilty to a charge of using the
mails to defraud and was fined in the federal courts. Whether there is
any connection between these two names, we do not know.
Reverting to the claims made by the Pulvane Laboratories that Pulvane
was “developed in a United States Army General Hospital by officers
of the Medical Department” the following statement has recently been
received by The Journal from Surgeon-General Ireland of the United
States Army:
“It has been brought to my attention that a concern in Des Moines,
Iowa, known as the Pulvane Laboratories, has issued a pamphlet in
which statements are made which would naturally lead medical men to
believe that the experiments, etc., referred to therein were made
with the approval of and more or less under the direction of the
Medical Department of the Army. I wish to say that this is not so;
that the Medical Department had nothing whatever to do with the
matter and that it thoroughly disapproves of the methods used by the
promoters of this concern.--(_From The Journal A. M. A., March 11,
1922._)
SAL HEPATICA
Sal Hepatica is a saline laxative sold by the Bristol-Myers Company of
New York. Little information is given, or, apparently, ever has been
given, concerning the composition of this product. Many years ago the
stock medical journal advertisement contained this statement:
“_Composition._--Sal Hepatica contains all of the Tonic, Alterative
and Laxative Salts of the celebrated ‘Bitter Waters’ of Europe,
especially those of Bohemia, as determined by actual chemical
analysis of these waters, and fortified by the addition of Lithium
and Sodium Phosphates.”[255]
[255] Some of the Sal Hepatica advertising has claimed that it “is a
saline combination with the addition of Sodium Phosphate and _Lithia
Citrate_!”
Sal Hepatica no longer “contains all the tonic, alterative and laxative
salts ...,” etc., for the label on a package recently purchased reads:
“SAL HEPATICA is an effervescent saline combination possessing
medicinal properties similar to the natural ‘Bitter Waters’ of
Europe, and fortified by the addition of Sodium Phosphate.”
In 1909, the _Druggists Circular_ published an analysis of Sal Hepatica
which showed that the preparation contained only 0.04 per cent. of
lithium phosphate. By referring to the two quotations just given
it will be noticed that today the manufacturers make no claim that
their preparation is fortified with any salt of lithium. A circular
accompanying recent trade packages states:
“Sal Hepatica is composed solely of harmless salts, being
absolutely free from Acetanilid, Phenacetin, Caffein, Calomel,
opium or coal tar derivatives.”
Since neither the names nor the amounts of the “harmless salts” are
mentioned, the composition of Sal Hepatica is secret. It is a trick
of the nostrum exploiter, old but ever popular, to mention numerous
drugs which his preparation does _not_ contain; it helps to distract
attention from the fact that he does not tell what the preparation
_does_ contain!
In the old-time medical journal advertisements, one reads, “Sal
Hepatica is the most powerful solvent of Uric Acid known.” (The same
advertisement as it appeared in those days in The Journal shows
that claim toned down to, “Sal Hepatica is a powerful solvent of
Uric Acid.”) In those easy going days, the Bristol-Myers Company
declared that “diabetes is treated with decided advantage by means
of Sal Hepatica ... it ... possesses the property of arresting the
secretion of sugar in the liver.” In the old days, too, Sal Hepatica
was recommended in the treatment of cirrhosis of the liver, Bright’s
disease, gravel, phthisis, etc.
The present advertising circular recommends Sal Hepatica as an
eliminant, laxative or cathartic in gout, autointoxication, “Bilious
Attacks,” rheumatism, acute indigestion, catarrhal conditions of
the stomach, pyorrhea, headache, dizziness, heart burn, “Summer
Complaints,” “Derangements of the Stomach and Liver,” skin diseases,
colic, alcoholic excesses, and as a “preventive of Seasickness.”
In 1914 the Council on Pharmacy and Chemistry published[256] a report
on Sal Hepatica declaring it secret in composition and sold under
exaggerated and unwarranted claims.
[256] J. A. M. A., Feb. 7, 1914, p. 472.
In view of the inquiries which The Journal continues to receive it
seemed worth while to make a chemical examination of the present-day
product. Accordingly specimens were purchased and analyzed in the
A. M. A. Chemical Laboratory. The report that follows was submitted by
the chemists:
“Sal Hepatica is a white, granular, odorless powder. It effervesces on
the addition of water in which it eventually dissolves. The aqueous
solution, after boiling to remove carbon dioxid, has an acid reaction
to litmus.
“Since a great many medicinal substances are sold in effervescent form,
and since practically no information is given by the manufacturer
concerning the composition of Sal Hepatica, it became necessary to
test for a considerable number of therapeutic agents. The absence of
acetanilid, acetphenetidin, alkaloids, ammonium salts, benzoates,
caffein, citrates, heavy metals, hexamethylenamin, magnesium,
potassium, salicylates and sugars was demonstrated by appropriate
tests. The presence of a carbonate (probably in the form of a
bicarbonate), a phosphate, a sulphate, a chlorid, tartaric acid, sodium
and traces of lithium was shown by qualitative tests.
“Quantitative analysis indicated that the composition of the specimens
examined was essentially as follows:
Sodium phosphate, anhydrous 4.4 per cent.
Sodium sulphate, anhydrous 26.5 per cent.
Sodium tartrate, anhydrous 12.7 per cent.
Sodium bicarbonate 19.5 per cent.
Tartaric Acid, free 20.8 per cent.
Sodium chlorid 8.9 per cent.
Lithium phosphate trace
Water of hydration (by difference) 7.2 per cent.
“From the results of the analysis, it appears probable that the
composition of the mixture before ‘granulation’ was approximately as
follows:
Sodium phosphate 4 per cent.
Sodium sulphate 25 per cent.
Sodium bicarbonate 30 per cent.
Tartaric Acid 30 per cent.
Sodium chlorid 8 per cent.
Lithium phosphate trace
Water of hydration (by difference) 3 per cent.
“Sal Hepatica, therefore, is essentially an effervescing mixture of
dried sodium sulphate (Glauber’s salt) and sodium tartrate with a
little dried sodium phosphate and table salt added. It is similar to
the effervescent artificial Carlsbad Salt described in the National
Formulary.
“In 1909 the _Druggists Circular_ published the following analysis of
Sal Hepatica:
Sodium phosphate 29.80 parts
Sodium sulphate (Glauber’s salt) 26.27 parts
Sodium bicarbonate (baking soda) 18.00 parts
Sodium chlorid (salt) 13.05 parts
Lithium phosphate 0.04 parts
Citric and tartaric acids (to make 100) 12.84 parts
“A comparison of the recent analysis with the earlier one would seem to
indicate that considerable changes have been made in the formula since
the first examination. The proportions of sodium phosphate have been
greatly reduced, while the sodium bicarbonate and tartaric acid have
been increased and the citric acid entirely eliminated.”
Sal Hepatica, then, is a simple effervescent saline laxative,
essentially secret in composition and sold under claims that would be
laughed at were the full formula of the product a matter of public
knowledge.--(_From The Journal A. M. A., Oct. 29, 1921._)
SALICON
“Salicon” is marketed by the K. A. Hughes Company, Boston, as “an
improved aspirin.” In a circular sent out to the public a little over a
year ago the following claims were made for it:
“We rendered aspirin absolutely harmless and yet retained all its
virtues as a medicine.”
“It positively will not depress the heart nor upset the stomach no
matter how large amounts of it are taken.”
“... the Massachusetts state medical authorities ... adopted its
use at all the state camps for fighting the Spanish influenza....”
The first two statements quoted above are obviously false. The third
statement might have been true although it seemed unlikely. A letter
was, therefore, written to the Department of Public Health of the
Commonwealth of Massachusetts and the claim of the K. A. Hughes Company
relative to the adoption of Salicon in all the state camps by the
“state medical authorities” was brought to their attention. The reply
of the department on this point was emphatic:
“The State Department of Health of Massachusetts did not endorse the
use of Salicon for any purpose.”
Some Salicon was purchased on the open market and submitted to the
A. M. A. Chemical Laboratory for analysis. Here is the chemists’ report.
“One original bottle of ‘Salicon’ (K. A. Hughes Company, Boston)
was submitted by the Propaganda department of The Journal to the
Association’s Chemical Laboratory for examination. The bottle contained
100 white tablets having an average weight of 0.407 gram (6.3 grains),
each. The amount of ash was 20.9 per cent. Qualitative tests indicated
the presence of magnesium, carbonate, starch, acetylsalicylic acid and
a trace of calcium; a very small amount of a petrolatum-like substance
was present. Alkaloids and drugs used for a laxative effect were not
found. The amount of acetylsalicylic acid extracted by chloroform was
50.7 per cent. The amount of magnesium present as magnesium oxid was
14.3 per cent. The amount of magnesium oxid derived from magnesium
carbonate U. S. P. is variable; but calculating on the lowest limit,
14.3 per cent. of magnesium oxid is equivalent to at least 35.5 per
cent. of magnesium carbonate. This figure agreed closely with that
obtained from the U. S. P., method of assay. The acetylsalicylic acid
was not combined with the magnesium. From the above, it may be stated
that each tablet consisted essentially of a mixture of 3.2 grains of
acetylsalicylic acid (aspirin), 2.2 grains of magnesium carbonate and
some starch. Although labeled 5 grains, each tablet did not contain 5
grains of the most active ingredient, acetylsalicylic acid.”
The same old story. An ordinary mixture of well known drugs put on the
market as a new discovery and foisted on the public under false and
misleading claims.--(_Correspondence in The Journal A. M. A., Feb. 5,
1921._)
SO-CALLED SECRETIN PREPARATIONS
In China the administration of powdered tiger-bone is--or was--a
favorite form of treatment in cases of supposed cardiac weakness. The
theory is, presumably, that the cardiac strength of the tiger would
be a good thing for the patient to acquire. Since many patients have
recovered after taking tiger-bone, and no one has proved that they
might not have died had they failed to take it, “clinical experience”
stands back of the treatment; and where is the skeptic so rash as
to challenge that? The Chinese physician believes in his tiger-bone
therapy, and, with the best interests of his patient at heart, insists
on obtaining absolutely true and authentic tiger-bone. Not satisfied
with the assertions of the dealers, the conscientious Chinese physician
subjects his tiger-bone to a kind of physiologic standardization. He
offers the bone in question to a dog! If it is an ox-bone--a frequent
form of substitution--the dog will seize and eagerly gnaw it, whereas,
according to all the teachings of Chinese pharmacognosy, if it is a
tiger-bone the dog will depart hurriedly with his tail between his
legs. Very foolish? Yes! But before we smile superciliously at the
Chinese medical man, let us turn to the report of the Council on
Pharmacy and Chemistry on “So-Called Secretin Preparations.”[257] After
reading this report let us put to ourselves, squarely and honestly,
the question: Has the attitude toward secretin therapy, of a certain
portion of those who represent Western modern medicine, really been
much more scientific than that of the Chinese medical profession toward
tiger-bone therapy? On the basis of a hypothesis scarcely less crude
and unsubstantiated than that which assumes that tiger-bone is of
value in heart disease, it has been assumed that secretin is of value
in gastro-intestinal diseases. On the ground of “clinical evidence”
scarcely more critical than that exhibited by our confrères in the
antipodes, it has been asserted that alleged secretin preparations
actually are efficious. Indeed, in one respect the methods of the
Chinese physician appear more scientific than those of his Western
brethren. To the best of his ability, the Oriental at least makes sure
that he is administering genuine tiger-bone; he does not rely on the
unverified word of his dealer alone. The American physician has not
been making the least effort to ascertain whether his supposed secretin
preparations are truly such; and, as a matter of fact, scientific
investigation seems to indicate that some of these products contained
no secretin at all! Whatever one may think of the validity of his test,
the Chinese physician does his best according to his lights. As to
“clinical experience,” Dr. Jacobi has well said that some people make
the same mistake a hundred times and call it “experience.”--(_Editorial
from The Journal A. M. A., Jan. 15, 1916._)
[257] Page 64.
SUCCUS CINERARIA MARITIMA
Another Illustration of One of the Weaknesses of the Federal
Food and Drugs Act
The Walker Pharmacal Company of St. Louis was, we understand, if it is
not still, one of the subsidiary concerns of the Luyties Homeopathic
Pharmacy Company. It has for years sold a nostrum, “Succus Cineraria
Maritima,” under the claim that by simply dropping this stuff into
the eye, twice daily, cataract and other opacities of the eye will be
cured. For instance:
“... the only remedy for the relief of cataract and other opacities
of vision, which stands before the medical fraternity on a firm
foundation of accomplished results....”
“... possesses a specific power in removing the obstruction to
vision.”
“In this class of cases [cataract] physicians can place reliance
on Succus Cineraria Maritima (Walker) which does not require the
services of a specialist but is simply dropped into the eye with an
ordinary medicine dropper twice daily....”
“... has been used with success in cataract, both lenticular and
capsular, pterygium and opacities of the cornea, softening the
opaque deposits, causing dissolution, and by its stimulating
properties, hastening absorption.”
Succus Cineraria Maritima is advertised to the medical profession in
true “patent medicine” style by means of testimonials from doctors,
obscure and deceased. The preparation is valueless for the purposes for
which it is sold and “has about as much effect on the dissolution or
dispersal of opacities due to organic changes in the lens as pouring
the same down the back of the patient’s neck!” More than five years ago
the Council on Pharmacy and Chemistry reported on the worthlessness
of the drug, Cineraria maritima, and, at the same time, The Journal
pointed out that the drug would have been forgotten long ago had it
not been for the prodigal use of printers’ ink by the Walker Pharmacal
Company in advertising its Succus Cineraria Maritima.
These facts are given for the purpose of refreshing the memory of our
readers and are but incidental to the object of this article. In due
time the federal authorities proceeded against the Walker Pharmacal
Company charging that Succus Cineraria Maritima was misbranded under
the federal Food and Drugs Act. The government chemists reported that
analysis “showed that the product was essentially an aqueous solution
of glycerin, boric acid and vegetable drug extractives carrying
tannin-like bodies.” The direct and inferential claims made in the
advertising matter accompanying the trade package were quoted by the
federal authorities, who pointed out that the Walker Pharmacal Company
was selling the nostrum under claims that would create in the minds of
the purchasers the belief that Succus Cineraria Maritima was a remedy
for cataract and other opacities of the eye causing impaired vision and
that it was a cure for senile cataract, trachoma, secondary opacities,
etc. These claims the government charged were “false and fraudulent in
that the same were applied to the article knowingly, and in reckless
and wanton disregard of their truth or falsity,” because “in truth
and in fact it was not, in whole or in part, composed of, and did not
contain, such ingredients and medicinal agents” as would produce the
therapeutic effects claimed.
[Illustration: Facsimile of a letter, dated October, 1916, suggesting
the use of “Succus Cineraria Maritima” as a cure for cataract and
other opacities of vision. Eight months previously (February, 1916),
the Walker Pharmacal Company had pleaded guilty to the charge that the
claims that “Succus Cineraria Maritima” was a cure for cataract and
other eye opacities were false and fraudulent and applied knowingly and
in reckless and wanton disregard of their truth or falsity. The federal
Food and Drugs Act does not apply to claims made in circular letters or
elsewhere than in the trade package.]
These charges put the matter flatly up to the Walker Pharmacal Company.
This company has for years been telling physicians that their stuff
_could_ and _would_ do just what the federal authorities insisted it
can _not_ and will _not_ do. Did the Walker Pharmacal Company attempt
to defend its claims? Did it demonstrate that Succus Cineraria Maritima
would cure cataract? Did it produce evidence of the numerous cases of
recovery from blindness or partial blindness which must have been
available if the preparation had the powers claimed for it? No! The
Walker Pharmacal Company in February, 1916, pleaded guilty--and was
fined a paltry $10 and costs.
This, however, is not the end of the story. The company was prosecuted
because it had published the false and fraudulent claims in the trade
package, thus bringing the claims within the purview of the federal
Food and Drugs Act. Had the Walker Pharmacal Company confined its false
statements to medical journal advertisements, to the circular letters
sent to physicians or to any other advertising matter not part of the
trade package, it could have snapped its fingers at the Food and Drugs
Act.
It was in February, 1916, that the Walker Pharmacal Company pleaded
guilty to the charge of making false and fraudulent claims for Succus
Cineraria Maritima. In October, 1916, they were still sending out
circular letters to physicians urging the use of Succus Cineraria
Maritima in the treatment of cataract and enclosing the usual booklet
of testimonials claiming cures for cataract and other opacities of the
lens and cornea!
[Illustration: Facsimile of some of the pages from the booklet that
accompanied the letter reproduced herewith. The obvious intent of
this booklet was to lead physicians to believe that Succus Cineraria
Maritima will cure “Opacity of the Cornea,” “Opacity of the Lens,”
“Senile Cataract,” “Incipient Cataract,” “Double Cataract,” etc.]
Can one conceive a better illustration of the inadequacy of the Food
and Drugs Act? The dishonest exploiter of proprietary medicines cares
little that the law requires him to keep within certain bounds of
truthfulness in the advertising that accompanies the trade package.
It isn’t the claims in the trade packages that sell the product; it’s
the advertising in medical journals, in circular letters, etc. Yet,
the Food and Drugs Act offers no check or curb on false statements or
fraudulent claims made for proprietary or “patent medicines” in any
other place than the trade packages.
A few weeks ago The Journal called attention to a flagrant case of
fraud; and at that time it said, “It is justifiable to assume that
when any man, whatever his business, admits in court that he has made
fraudulent claims and then continues to make the same claims through
channels that are not controlled by penal enactment, that man’s
standard of business ethics is such that the public needs protection
against it. There are many such men in the ‘patent medicine’ world. The
only way in which the public may properly be protected against being
defrauded in such cases is for the federal Food and Drugs Act to have
its scope extended to cover _all_ advertising of the products coming
under the purview of the act.”--(_From The Journal A. M. A., March 17,
1917._)
TEKARKIN
Edward Percy Robinson’s “Cure” for Cancer
From various parts of the country The Journal has received a sixteen
page pamphlet, _Therapeutic Leaves_. The publication, which has
a saffron colored cover, is said to be published by the National
Bio-Chemical Laboratory, Mount Vernon, N. Y. The National Bio-Chemical
Laboratory seems to be a style used by Dr. Edward Percy Robinson. The
“editorial offices” of _Therapeutic Leaves_ are given as “501 Knox
Bldg., 5th Ave. at 40th St., New York,” which is a roundabout way of
describing 452 Fifth Ave., the office address of Edward Percy Robinson.
The first number (February, 1921) of _Therapeutic Leaves_ gives the
names of the “editors” as “E. P. Robinson, M.D., and W. A. Jenner,
B.A.” In addition, there is “Assistant Editor, F. J. Geiger,” and
“Gen’l Manager, Beverly K. Robinson.” The first and second numbers
of _Therapeutic Leaves_ (February and March, 1921) are practically
identical, being evidently printed from the same plates. _Therapeutic
Leaves_ purports to be a periodical published as “a medium for the
dissemination of knowledge, pertaining to therapeusis.” Actually, it
is an advertising medium dealing with the products of the National
Bio-Chemical Laboratory: “Osmo-Calcic Solution,” “Tekarkin” and
“Osmotic Mangano-Potassic Solution.”
These preparations are said to be the “formulas” of Dr. Edward Percy
Robinson who lives in Mt. Vernon, N. Y., and has an office at 452 Fifth
Ave., New York City. They are used by Dr. Robinson in the treatment
of cancer. At an earlier stage they seem to have been known under
different names: “Tekarkin” was first “Hypotonic Sal-Cella” and then
“Neoanabolin-X;” “Osmo-Calcic Solution” was “Osmotonic Calcic” while
“Osmotic Mangano-Potassic Solution” was “Osmotonic Drops.” The three
solutions are put up in one package containing 4 c.c. (about 65 minims)
of “Tekarkin” and 1 ounce each of the other preparations. The package
sells for $10.00. “Remittance with order ... We have no agents.”
[Illustration]
Most of the material in _Therapeutic Leaves_ is a rehash of four
papers published by Edward Percy Robinson in the New York _Medical
Record_ of various dates between September, 1917, and July, 1920. In
these Robinson advances the theory that cancer is caused by an excess
of sodium chlorid (table salt) in the blood and tissues and that it
can be cured by administering a solution of potassium nitrate. Such a
treatment sounds ideally simple. One might assume that all that was
necessary was to make up a solution of potassium nitrate and inject it.
One might further wonder how it would be possible to commercialize such
a “treatment.” “Homemade solutions,” says Dr. Robinson, “are apt to be
disappointing.” Their use is likely to cause “considerable swelling at
the site of an injection, accompanied with tenderness and some heat.”
Moreover, “a wide hyperemic area with red blotches has been observed
in a number of instances.” In order to avoid “accidents of this sort”
which would “bring discredit upon an excellent agent,” Dr. Robinson,
“after considerable experimental work” has obtained “a solution of this
chemical which would meet the ideal requirements.” This is available
under the name “Tekarkin.” Dilute potassium nitrate solution sold under
the name “Tekarkin” sells for $67 an ounce. The physician can make his
own solution, of the purest and highest grade potassium nitrate on the
market, at an expense, for the chemical, not exceeding 5 cents an ounce.
_Therapeutic Leaves_ also contains the usual number of those “clinical
reports” which bulk so large in the literature of “cures” for cancer.
Then there is a full page advertisement of a side-line of the National
Bio-Chemical Laboratory: “Vitamines (Compressed) Tekarkin Brand;” “They
have a meaty taste.”
The medical profession, naturally, is interested in knowing more about
the physician who admits that he has discovered the cause and cure of
cancer. According to our records, Edward Percy Robinson was born in
1871 and was graduated in 1897 by Bellevue Hospital Medical College. He
was licensed in New York State the same year and has practiced in New
York City continuously since that time. He is not, and apparently never
has been, a member of his local medical society.
In 1914 Robinson was specializing in “facial contouring.” One piece of
advertising purports to be the reprint of an interview with “Dr. E. P.
Robinson, Specialist, as he sat in his office at 116 West 39th Street,
having questions fired at him by the reporter.” Thus Dr. Robinson:
“There are physicians everywhere who abandon the general, or
family, practice of medicine, to devote their life to some
specialty. My specialty is the improvement of the facial features
and the beautifying of the shoulders, neck and arms. I round
out hollow cheeks, build up the neck, eradicate wrinkles, make
irregular noses perfect and remove defects by a process which
is my own secret. I claim no superhuman power or ability; I have
simply bent my whole professional study and energy to the one line
of remodeling--so to speak--the human features, and I employ only
scientific methods and aids in my operations.”
In another piece of advertising, a little booklet bearing Edward Percy
Robinson’s name, we find the following:
“This is what I accomplish....
“Remove all wrinkles and traces of age from the forehead, or about
the eyes and mouth. Lift sag from cheeks and chin.
“Round out hollow cheeks.
“Remove depressions and defects from the chin.
“Build up the neck and shoulders.
“Build up and enlarge the bust.
“Round out and give symmetry to unshapely arms and remove the lines
of age from the hands.
“Correct many of the defects not mentioned here, but which may be
possessed by exceptional cases.”
[Illustration: Reproduction (reduced) of some advertising matter
issued in 1914 when Edward Percy Robinson was specializing in “facial
contouring.”]
Still another advertising leaflet purports to be a reprint of an
“editorial” from the _Mercantile and Financial Times_ of March
11, 1914. It is a pretentious puff of Robinson, telling about his
“scientific attainments” and his marvelous secret preparations used
in “Youthifying the Face.” The _Mercantile and Financial Times_ is
an utterly discredited sheet run for the purpose of selling what
appear to be editorial comments. Such “editorial” puffs are paid for
through the purchase of a certain number of copies of the paper by
the party who desires the publicity. The Associated Advertising Clubs
of the World exposed this publication in a special bulletin issued
in June, 1919, and described it as an “example of publications that
serve as convenient tools of fake promoters.” In 1911 the _Mercantile
and Financial Times_ published an “editorial” endorsement of the
consumption cure “Nature’s Creation.” It has done the same for a fakish
device known as the “Ideal Sight Restorer.” It published a puff on the
“Oxypathor,” a swindle so preposterous that the exploitation of this
“gaspipe” fake was debarred from the U. S. mails and its exploiter was
sent to the federal penitentiary.
[Illustration:
+ - - - - - - - - - - - - - - - - - - - +
| The Jean Downs Co., |
| New York |
| |
| My dear Mrs. Downs, |
| |
| The package of your “Get Slim” remedy for obesity has |
| been given to a patient of mine with beneficial results. |
| |
| In observing the action of the remedy I noted no laxative |
| effect on the bowels, or any disturbance of the stomach. |
| |
| In fact there were no physical sensations that any |
| remedy had been taken, and there was a very satisfactory |
| reduction in weight. |
| |
| “Get Slim” remedy, being a purely vegetable combination |
| is not fraught with any risk to the individual’s health, |
| and may be safely given. |
| |
| I would not hesitate to prescribe it for a child |
| suffering from obesity. |
| |
| This statement is based on the fact that I am acquainted |
| with the ingredients entering into its manufacture. |
| |
| I would add that this remedy for obesity might be intro- |
| duced to the regular physicians with some advantage to |
| you. |
| |
| Yours truly, |
| E P ROBINSON M D |
| 1402 Broadway |
+-----------------------------------------------------------+
Reproduction (reduced) of a testimonial for an obesity
cure fake, “Get Slim.” The A. M. A. chemists reported that this
“vegetable combination” consisted of baking soda and pink-tinted
tartaric acid and sugar.]
We also find in our files a testimonial signed E. P. Robinson, M.D.,
1402 Broadway (Edward Percy Robinson’s address in 1912), extolling
the virtues of a foolish piece of quackery, the obesity cure “Get
Slim.” This nostrum was exposed in The Journal some years ago and
was also exposed by Dr. Wiley in _Good Housekeeping_. The “Get Slim”
concern sued _Good Housekeeping_ for libel but a jury decided that
_Good Housekeeping_ had told the truth. In the “Get Slim” testimonial
Robinson is quoted as saying that he is “acquainted with the
ingredients entering into its manufacture” and he describes it, as did
the “Get Slim” concern, as “a purely vegetable combination.” The fact
is the Association’s chemists found this “purely vegetable combination”
to consist of sugar and tartaric acid, each colored pink, and baking
soda.
And this is the gentleman who claims to have discovered the cause of,
and offers for sale a cure for, one of the most baffling scourges known
to modern medicine--cancer. Except for the articles that have been
published during the past three years in the _Medical Record_, we are
unable to find anywhere in representative medical literature anything
to indicate that Edward Percy Robinson can lay any claim to special
knowledge of, or skill in the treatment of, cancer. What we do find are
advertisements describing Edward Percy Robinson’s alleged abilities
as a “face beautifier,” puffs from utterly uncritical or discredited
sources and a testimonial to the value of a preposterous “fat cure”
fake.
With the best brains of the world at work on the problem of cancer, it
is reasonable to assume that any man who has found out even a little
more than has previously been discovered or is able to accomplish
even a little better results than the average in the treatment of this
dreaded disease, would be well known to scientific medicine.
* * * * *
After this article was in type physicians began sending in No. 3
(April, 1921) of _Therapeutic Leaves_. This is still another reprint
of Nos. 1 and 2, with minor changes. In the first two, Tekarkin is
described as “a solution of potassium nitrate of special strength;” in
No. 3 it becomes “a special solution containing potassium nitrate.”
In Nos. 1 and 2, Robinson described an alleged case of “Cancer of the
Rectum _Treated_ with Tekarkin.” In No. 3 this becomes “Medicinal
Treatment _Cures_ Cancer of the Rectum.” In No. 3 the names of the
editors, assistant editor and general manager are eliminated.
[Illustration]
The inside back cover of No. 3 contains an advertisement of Tekarkin,
in which physicians are warned that “Cancer of the Lung May Present
Diagnostic Signs of Tuberculosis.” It contains the further startling
information that the particular micro-organism responsible for
pulmonary tuberculosis is the Klebs-Loeffler bacillus! Thus:
“The Klebs-Loeffler bacillus may find a suitable habitat in a
malignant area of lung tissue and thrive therein. The presence of
the bacillus does not necessarily exclude the presence of cancer.
A chronic cough with blood-streaked sputum may be the result of
tuberculosis and cancer.”--(_From The Journal A. M. A., May 28,
1921._)
TYREE’S ANTISEPTIC POWDER AGAIN
The “Ethical and Commercial Requirements” of the Drug Business
“I am fond of the retail drug business and follow it every day of
my life. I know and observe to the fullest extent its ethical and
commercial requirements.” This from a circular letter recently received
by physicians, and signed J. S. Tyree, who asks that he be forgiven for
writing you personally, but there are several reasons why he thinks
the circumstances warrant it. All of which is preliminary to calling
attention to an enclosure, which accompanies the circular letter, and
is described as a “short memorandum” submitted for “your consideration.”
The “memorandum” is a four-page leaflet of which three pages are
devoted to “Tyree’s Antiseptic Powder.” One of these three pages
is a reproduction of a letter on the stationery of the Surgeon
General’s Office of the War Department, and signed “W. M. Gray,
M.D., Microscopist, Army Medical Museum; Pathologist to Providence
Hospital.” The letter describes a series of “bacteriological and
comparative tests” made by Dr. Gray with Tyree’s Antiseptic Powder.
The entire second page of the circular is given over to the results of
these bacteriologic tests which compare various strengths of Tyree’s
Antiseptic Powder with “mercuric bichlorid,” phenol and formaldehyde.
The physicians who received this advertising material in April, 1919,
might easily overlook the fact that Dr. Gray has been dead several
years, that the letter which is reproduced is dated Jan. 3, 1890, and
that the bacteriologic tests were made in 1889--thirty years ago!
The Council on Pharmacy and Chemistry in 1906[258] published the
results of an analysis of Tyree’s Antiseptic Powder which showed that
although the stuff was advertised as a mixture of borax and alum, it
was in fact essentially a mixture of zinc sulphate and boric acid. The
publication of the Council’s report in 1906, showing the falsity of the
formula, brought out the admission that the composition had recently
been changed. Certain it is, however, that for at least a decade past,
the Tyree product has been a zinc sulphate-boric acid preparation.
Yet, according to the manufacturer’s own statement, Tyree’s Antiseptic
Powder in 1889, when Dr. Gray made his bacteriologic tests, was an
entirely different substance from the present mixture.
[258] At this time Tyree’s Antiseptic Powder was an “ethical
proprietary”--heaven save the mark!--and advertised only to physicians.
Later, as _The Journal_ has shown, it entered the “patent medicine”
field as “ideal for douche” and the “best preventative known.” The
articles on this nostrum are reprinted in the ninth edition of “The
Propaganda for Reform.”
Here then we have a manufacturer publishing in 1919, in behalf of
a certain product, tests that were made in 1889 with a product of
different composition, although of the same name! Is this observing “to
the fullest extent” the “ethical and commercial requirements” of the
“retail drug business”?
There is no scientific excuse for such a mixture as Tyree’s Antiseptic
Powder. If, however, physicians feel that they must use an irrational
conglomeration such as this, why not prescribe Pulvis Antisepticus,
N. F.? Like the Tyree product, this, too, is essentially a mixture
of zinc sulphate and boric acid, with minute amounts of phenol,
eucalyptol, menthol and thymol, to say nothing of a dash of salicylic
acid. This official article has at least the virtue of constancy of
strength, composition and purity assured under the federal Food and
Drugs Act.--(_From The Journal A. M. A., May 17, 1919._)
WHEELER’S TISSUE PHOSPHATES
“The Commissioner of Health directs me to call to your attention
the enclosed advertisement issued by T. B. Wheeler, M.D., Company,
Montreal, Canada, in which the name of the Association’s _Journal_
is being used.”
Accompanying this brief note to The Journal from the secretary of Dr.
Haven Emerson, Commissioner of the Department of Health of the City
of New York, was a four page leaflet devoted to the exploitation of
“Wheeler’s Tissue Phosphates.” The trend of the circular is to lead
the average reader to infer that The Journal of the American Medical
Association has endorsed Wheeler’s Tissue Phosphates. For example, in
describing the preparation one reads:
“It embodies ... the best recent scientific opinion concerning
the treatment of the disease (tuberculosis) as stated ... by the
official Journal A. M. A.”
Elsewhere in the circular The Journal’s criticisms of the
hypophosphites and the glycerophosphates (proprietary preparations
which are competitors of the Wheeler product) are quoted and twisted
into a tribute to the ingredients of Wheeler’s Tissue Phosphates.
Garbling quotations, distorting statements, separating phrases from
their contexts and omitting qualifying clauses, all for the purpose
of making out a case for some proprietary remedy is a trick as old as
quackery itself. That it should be used in advertising Wheeler’s Tissue
Phosphates is entirely fitting. Obviously, the T. B. Wheeler, M.D.,
Company esteems the opinion of The Journal on pharmacologic matters.
This being the case, it should, in the interest of truth and scientific
accuracy, publish in its advertising circulars just what The Journal
has said about Wheeler’s Tissue Phosphates. It could not do this better
than by quoting from a recent editorial note which commented on a
report of the Chemical Laboratory on this preparation. Here is part of
the The Journal’s comment:
“‘Wheeler’s Tissue Phosphates’ is an unscientific shotgun mixture
whose most active and powerful drug is the alcohol it contains.
That it was not years ago relegated to the realms of obsolete
and discarded preparations is a commentary alike on the lack of
scientific discrimination and on the power of advertising.”
Here we have “Wheeler’s Tissue Phosphates” stripped of the verbal
camouflage with which its exploiters have invested it.--(_Editorial
from The Journal A. M. A., Sept. 22, 1917._)
BRIEFER PARAGRAPHS
Alcresta Lotion
_To the Editor_:--What is the composition of Alcresta Lotion?
L. T. A. Hotten, M.D., Paris, Idaho.
According to a circular in our files, “Alcresta Dental Lotion-Libby”
contains “Emetin, the active amebicidal principle of Ipecac, together
with Benzoic Acid, Thymol, Eucalyptol and Aromatics.” The theory
that emetin is an active amebicide against pyorrhea alveolaris has
been exploded. In this connection, it is interesting to note that
the firm does not list the product in the latest catalogue in our
files.--(_Query from The Journal A. M. A., Oct. 29, 1921._)
Calcidin Tablets (Abbott)
_To the Editor_:--What is the composition of calcidin tablets
(Abbott) and what is their value?
J. S.
ANSWER.--Calcidin is claimed to be a mixture of iodin, lime and starch.
In contact with water, the iodin and lime react to form calcium iodid
and calcium iodate. By the acid of the gastric juice, the calcium iodid
and calcium iodate are decomposed with liberation of free iodin. The
administration of calcidin tablets amounts to giving free (elementary)
iodin. In the past, the advertising for calcidin has contained the
unwarranted claim more or less directly that it was the most effective
and only noninjurious preparation of iodin for internal use, and that
it possesses all of the valuable properties of the iodin with all of
the objectionable effects left out. So far as we know, the effects
produced by the administration of free iodin do not differ from those
produced by the administration of iodids and, therefore, calcidin has
no advantage over the iodids, such as sodium iodid.--(_Query in The
Journal A. M. A., Sept. 25, 1920._)
Di-Crotalin Treatment of Epilepsy
_To the Editor_:--Do you have any literature or information
relative to the Di-Crotalin treatment for epilepsy? I will be
very grateful if you can furnish information as to method of
preparation, rationale of the treatment, etc.
R. C. Decker, Captain, M. R. C.,
U. S. Soldiers’ Home, Washington, D. C.
ANSWER.--Di-Crotalin is a rattlesnake venom preparation sold by the
Swan-Myers Company of Indianapolis as a “Treatment for Epilepsy,
Chorea, Bronchial Asthma, Chronic or Hereditary Nervous Headache,
Nervous Prostration Incident to Change of Life, Hysteria-Mania,
Insomnia, Neurasthenia, etc.” Dr. Thomas J. Mays of Philadelphia
advocated the use of rattlesnake venom for tuberculosis. Later his
former assistant, Dr. R. H. Spangler, used the same material in the
treatment of epilepsy. That any measure of success sufficient to
justify the adoption of the rattlesnake venom or crotalin treatment
for epilepsy has resulted is not to be concluded from the available
reports. Still less evidence is there for the use of rattlesnake
venom in the list of conditions for which the Swan-Myers Company has
recommended its preparation. There are a number of good reasons why a
cautious physician will shun the administration of this treatment and
advise against it. J. F. Anderson, working in the hygienic laboratory
of the United States Public Health Service, reported a death from the
crotalin treatment in consequence of infection, and reports that the
market supply of crotalin solution and crotalin tablets is highly
contaminated. He also found both crotalin and crotalin solution to
vary in activity. The use of rattlesnake venom was discussed in The
Journal, March 15, 1913, p. 850.--(_Query in The Journal A. M. A., Aug.
17, 1918._)
Estivin
_To the Editor_:--What is “Estevin,” or something like that? It is
said to be good in hay-fever.
Constant Reader.
ANSWER.--The product called “Estivin” is sold by Schieffelin and
Company, New York. A request for a statement of the composition of this
preparation sent to Schieffelin and Company by the Council on Pharmacy
and Chemistry brought the indefinite and, therefore, meaningless
statement that “‘Estivin’ is an extract of Rosa Gallica containing no
alcoholic or foreign ingredients.”--(_Query from The Journal A. M. A.,
Nov. 12, 1921._)
Iron Arsenite
_To the Editor_:--Can you inform me how iron arsenite can be
prepared for subcutaneous injection? A commercial firm furnishes
physicians with ampules of arsenite of iron. Is this really
arsenite of iron?
S. H. Kempner, M.D., New York.
ANSWER.--Ferric arsenite (iron arsenite) is in itself relatively
insoluble in water, but may be treated with ammonium citrate, the
resulting product thus being soluble; the latter substance was
at one time described in New and Nonofficial Remedies as “Ferric
Arsenite, Soluble” and is sometimes sold as a solution in ampule
form. In 1912, the Council on Pharmacy and Chemistry deleted “Ferric
Arsenite, Soluble” from New and Nonofficial Remedies because “one
cannot, in administering Ferric Arsenite, Soluble, give a useful
dose of iron without giving too much arsenic; and, vice versa, one
cannot give a safe dose of arsenic without giving too little iron.”
The Council, therefore, held the preparation to be irrational and
unscientific.--(_Query in The Journal A. M. A., Feb. 19, 1921._)
K-Y Lubricating Jelly
_To the Editor_:--1. What is the composition of “K-Y Lubricating
Jelly”? 2. Can you furnish a formula for a simple nongreasy
lubricating jelly?
S. T.
ANSWER.--1. The composition of “K-Y Lubricating Jelly” has not
been divulged. Examination of the advertising matter reveals only
meaningless statements, such as: “This is a judicious combination of
vegetable products ... Combined in well balanced proportions with
non-irritating antiseptics ...,” “It incorporates a sufficient quantity
of mild antiseptics (of the Thymol class) ...” and “... contains _NO_
formaldehyde.”
2. Probably a simple tragacanth jelly, which can be made cheaply, will
produce the same effects as those of the proprietary preparation. The
following formula was published by Mr. J. K. Thum, apothecary at the
German Hospital, Philadelphia (_Druggists Circular_, September, 1915,
p. 586):
LUBRICATING JELLY
Tragacanth, whole 3 gm.
Glycerin 25 c.c.
Phenol 1.5 gm.
Distilled water, a sufficient quantity to make 300 c.c. The
tragacanth is broken in small pieces, and put into a wide-mouthed
bottle; the other ingredients are added and the bottle frequently
shaken.
In regard to this formula, Mr. Thum writes:
It has been used in our gynecologic department for years.... For
the last six years we have been dispensing it in collapsible tubes
throughout the hospital for general work.--(_Correspondence in The
Journal A. M. A., May 12, 1917._)
“Nikalgin”
_To the Editor_:--_Collier’s_ has a special article this week on
“Nikalgin.” Have you any information on this subject? It sounds
like nostrum stuff.
P. R. Minahan, M.D., Fond du Lac, Wis.
ANSWER.--“Nikalgin” is said to be the “invention” of Gordon Edwards, an
engineer. Large claims for its anesthetic and antiseptic virtues have
been made. While no very definite information seems to be forthcoming
regarding the preparation, it has been said to be “composed of quinin,
hydrochloric acid and urea.” This would indicate that “Nikalgin” may
be nothing more wonderful than the well known local anesthetic, quinin
and urea hydrochlorid, the _Quininae et Ureae Hydrochloridum_ of the
U. S. Pharmacopeia, or a modification of it.--(_Query in The Journal
A. M. A., Sept. 22, 1917._)
Pertussin and Syrup of Thyme
_To the Editor_:--A short time ago I received a sample of
“Pertussin” and used some in an obstinate case of bronchitis
with excellent results. I have since received a catalog from a
pharmaceutical firm, which advertises syrup of thyme. I have
searched for a formula to make my own syrup of thyme, but have not
been able to find one. Will you publish one?
E. F. Benner, M.D., Salfordville, Pa.
ANSWER.--The subjoined formula yields a product very similar to
“Pertussin” in taste, flavor, composition, and probably in activity as
well:
Fluidextract of thyme 15 c.c.
Glycerin 15 c.c.
Syrup to make 100 c.c.
The original German preparation contained 1.5 gm. of sodium bromid
in each hundred cubic centimeters, and this might be added to the
foregoing formula with advantage, so far as action is concerned.
However, a sample of “Pertussin” purchased in the open market in the
United States failed to respond to tests for bromids.
As fluidextract of thyme is not official, this formula is presented as
furnishing an acceptable preparation:
Thyme, in No. 60 powder 100 gm.
Moisten with a mixture of:
Water 25 c.c.
Alcohol 15 c.c.
Glycerin 10 c.c.
After standing five hours, pack in a percolator. Exhaust with a
menstruum of alcohol, 1 volume, and water, 3 volumes. Reserve the first
85 c.c. of percolate. Concentrate the weak percolate to a soft extract
and dissolve in the reserved portion. Make up to 100 c.c. by addition
of a mixture of alcohol, 1 volume, and water, 3 volumes.
Other aromatic expectorants, such as terebene, terpin hydrate or
creosote, might be expected to have similar but greater effect in
chronic bronchitis. (_Query in The Journal, A. M. A., March 27, 1920._)
Quinin and Urea Hydrochlorid
_To the Editor_:--Could you tell me why quinin and urea
hydrochlorid has not become more popular for local anesthesia? Is
it less efficacious or more toxic than other preparations? If it is
useful, can you name some trustworthy firm or brand? Please omit my
name in answering.
L. F. C., M.D., Mexico.
ANSWER.--Quinin and urea hydrochlorid “has the actions of quinin.
When injected hypodermically it exerts an anesthetic action much more
prolonged than that of cocain” (Useful Drugs, Ed. 4, 1920, p. 127).
It has been pointed out editorially in The Journal (Feb. 14, 1920,
p. 462) that quinin has been regarded for more than half a century
by toxicologists as a protoplasmic poison capable of destroying
various forms of animal and vegetable cells, and hence it need not be
surprising that tissue necrosis may be produced by strong solutions
of the quinin salts. That this deleterious reaction actually does
occur and has militated against the general use of quinin and urea
hydrochlorid is confirmed by the report of the Committee on the
Advantages and Disadvantages of Local Anesthesia in Nose and Throat
Work (The Journal, July 31, 1920, p. 315). To quote:
The only local anesthetic that produces edema and sloughing is
quinin and urea hydrochlorid. So many statements were found in the
literature that this anesthetic has been abandoned in other fields
of medicine because of edema and sloughing, that writers who had
presented favorable reports in nose and throat operations were
communicated with by your committee. One writer who had recorded
390 cases of tonsillectomies extolling this anesthetic, which he
had used for four years and is still so recorded, now states that
he has not used it in two years, although no publication has been
made retracting his former endorsement. Still another writer, who
stated that quinin-urea came nearest the ideal local anesthetic,
now states that he has ceased using it. Your committee finds that
as far as nose and throat operations are concerned, this drug has
practically gone into “innocuous desuetude.”
The anesthesia produced by this drug at the time of operation is
good and the recovery of the patient might often be enhanced by its
use if it did not have the serious drawback. The product is official
in the U. S. Pharmacopeia, and may be obtained from any reputable
pharmaceutical house.--(_Query in The Journal A. M. A., Aug. 21, 1920._)
Ricord Pills and House Organ Therapeutics
_To the Editor_:--My mail is frequently cluttered with
pseudo-scientific data from various manufacturers of proprietary
remedies which contain as much real scientific information as the
_Police Gazette_. I am enclosing a sample page of such a periodical.
The article has been so cleverly worded in the first paragraph, as to
impress the unthinking with the idea that sodium cacodylate is superior
to arsphenamin, when we know in reality that sodium cacodylate has
been proved practically worthless in syphilis (_vide_ “Venarsen”). One
case is reported, in which twenty injections of sodium cacodylate were
administered intravenously, from October 23 to December 14. On December
18, a Wassermann test proved negative, it had been strongly positive on
October 20, but during the same interval from October 23 to December
14, the patient had been taking by mouth “Ricord pills” each containing
half a grain of yellow iodid of mercury; granted that he had taken
these pills regularly, during all that time, it might well be that
the Wassermann would be sharply influenced by them. Again, a negative
Wassermann in the midst of treatment proves little; it might be
positive again in a few days. The article stimulates the further use of
a product of known worthlessness in the treatment of syphilis. How any
one can use sodium cacodylate in preference to arsphenamin in syphilis
is beyond me. If I mistake not, the Propaganda Department has not taken
up the matter of these various pamphlets of the drug companies, such
as the _Doctor’s Factotum_, _Therapeutic Notes_, etc., lauding to the
skies such articles as “Seng,” “Cactina Pillets,” etc., _ad nauseam_.
The saddest part of the whole thing is that it must bring returns from
the unthinking, otherwise they would soon disappear, which would be a
great relief for the scrubwomen who empty our waste baskets.
Paul E. Bechet, M.D., New York.
[Comment.--The “sample page” sent by Dr. Bechet is from the
March-April, 1918, number of Parke, Davis & Company’s _Therapeutic
Notes_. It contains an “Original Communication” on “The Treatment of
Syphilis with Sodium Cacodylate, by Adolph Lappner, M.D., Detroit,
Mich.” The “article,” while nominally devoted to the praise of sodium
cacodylate, is virtually a puff for “Ricord Pills.” a Parke, Davis
& Co. product.]--(_Correspondence in The Journal A. M. A., July 13,
1918._)
Stannoxyl
_To the Editor_:--I am very anxious to know whether tin or stannous
oxid (SnO) has or has had any place among useful drugs. I have seen
such a prescription given in the treatment of mucous colitis, and
would be very glad to learn what its use may be.
Carlos Manuel Garcia, M.D., Havana, Cuba.
ANSWER.--Recently, on the assumption that tin workers are less troubled
with boils than the average person, two French investigators proposed
the use of tin compounds in the treatment of staphylococcic infections.
Based on their work, a proprietary preparation--Stannoxyl--has
been placed on the market which is claimed to be “composed of
stannous oxide and specially purified metallic tin.” Absurd claims
are made for the product: for instance, “... We have no hesitation
in offering STANNOXYL--in Tablets or Cachets--as the only true
specific for diseases of Staphylococcus origin.” The available
evidence is unconvincing and in no way warrants such exaggerated
statements.--(_Query in The Journal A. M. A., March 6, 1920._)
_To the Editor_:--I was much interested in your answer to a query
about Stannoxyl (The Journal, March 6, p. 629). I submit the following
experience as a confirmatory note:
While serving with the Royal Army Medical Corps in Egypt, I for some
time had charge of the medical division of a hospital in which most
of the skin diseases occurring among soldiers in the district were
treated. The most common conditions were boils and septic sores,
chiefly due to staphylococcal infection, though several of the latter
cases were diphtheritic. The treatment adopted was that in ordinary
use, namely, incision and evacuation of pus, application of antiseptic
dressings, and in most cases employment of the specific vaccine. It was
possible to judge of the efficacy of any variations of treatment, as
there were always plenty of cases undergoing the usual treatment with
which the results could be controlled.
An available supply of Stannoxyl, a proprietary remedy consisting of
a mixture of metallic tin and tin oxid, enabled me to give it a fair
trial in full doses in eight cases of boils of average severity, in
which culture revealed the infecting organism to be _Staphylococcus
aureus_. The boils were treated locally as usual, but no vaccine was
given. No improvement could be demonstrated in these cases that could
not be shown in other cases similarly treated with the omission of
Stannoxyl; in fact, three of the treated cases were much longer in
clearing up than the untreated controls. Eight cases do not constitute
a very large series from which to draw conclusions; but if the
preparation were as good as the descriptive literature would lead one
to believe, one should have expected an evident result in at least one
of these cases.
It has been stated that Stannoxyl does not inhibit the growth of
staphylococci, but only renders the growth less virulent. It is known
that a certain amount of tin may be absorbed from the intestine, and
Salant, Rieger and Treuhardt have shown that in certain cases tin
may be retained for some time in the skin; but it is questionable
whether, when preparations of tin are given by mouth, any reaches
the staphylococci in the boils, or at any rate enough materially to
influence their growth or virulence.
In the cases treated by me, the results did not at all suggest that
Stannoxyl was a “specific for diseases of staphylococcal origin.”
J. W. C. Gunn, M.A., M.B., Ch.B., Cape Town.
Professor of Pharmacology, University of Cape Town.
--(_Correspondence in The Journal A. M. A., Nov. 20, 1920._)
Syphilodol
_To the Council on Pharmacy and Chemistry_:--If you have not
already done so, will you kindly examine and report on “Syphilodol”
advertised in the enclosed pamphlet?
B. C. Pedersen, M.D., New York.
_To the Editor_:--Have you any information concerning the enclosed
half page advertisement [of Syphilodol] from the _Urologic and
Cutaneous Review_?
Edward S. Newell, M.D., Pelham, N. Y.
_To the Editor_:--I am enclosing an advertisement for a substance
called “Syphilodol” manufactured in New York. Am not familiar with
this article nor have I seen it advertised in the higher class
journals. Can you tell me whether The Journal’s department of New
and Nonofficial Remedies has passed on this article or whether you
have any data concerning it? It looks a trifle fishy to me.
Louis Leroy, M.D., Memphis, Tenn.
_To the Editor_:--I am sending the enclosed correspondence
[Syphilodol letters] to you as it looks as if it might have some
interesting features from the point of view of your nostrum
department.
Isadore Dyer, New Orleans, La.
ANSWER.--These are but some of the inquiries that have been received on
this subject and it is encouraging to note the scientifically critical
attitude of physicians toward new therapeutic agents. According to the
French Medicinal Company, Inc., which markets this product, “Syphilodol
is a synthetic chemical product of silver, arsenic and antimony....”
Nowhere in the advertising matter is there any more definite statement
as to the composition of this new “synthetic” than that just quoted.
The product is now under examination in the Association’s laboratory
and when this is completed a more detailed report will doubtless be
forthcoming. At present the work has progressed sufficiently to show
that Syphilodol tablets contain considerable quantities of mercury!
Although the advertising leaflets claim that the preparation is
“the formula of the late Dr. Alfred Fournier of Paris” and had been
exhaustively tested by Metchnikoff, who is alleged to have found
it superior to salvarsan and neosalvarsan, yet, strange to say, a
careful search of French medical journals fails to show any reports on
Syphilodol. _Verb. sap._--(_Query in The Journal A. M. A., Feb. 23,
1918._)
Thialion
_To the Editor_:--Kindly inform me regarding thialion, manufactured
by the Vass Chemical Company, Danbury, Conn. Please omit my name
and address in answering in The Journal.
H. C. W.
ANSWER.--Thialion is an heirloom of the days when lithium salts were
supported to be nature’s antidote for all kinds of ailments, supposedly
due to excess of uric acid. It was advertised as a uric acid eliminant
and therefore good for all kinds of diseases. The Council on Pharmacy
and Chemistry published a report on thialion in The Journal, Nov.
3, 1906. At that time thialion was advertised by the Vass Chemical
Company as a “laxative salt of lithia” with the chemical formula
“3Li₂O.NaO.SO₃.7HO,” and an elaborate structural formula was also
furnished. The Council reported that the product was not a definite
chemical compound, but a mixture consisting chiefly of sodium sulphate,
sodium citrate and small amounts of lithia. In recent advertisements,
thialion is referred to as “A Non-Effervescing Lithiated Laxative
Salt,” “a non-hygroscopic, non-deliquescent, granular salt of lithia,”
etc., but the chemical formula does not appear, nor is any definite
statement of composition furnished. According to this advertisement,
the “indications” for thialion are: “gout, rheumatism, uric acid
diathesis, constipation, acute and chronic, sluggish liver, Bright’s
disease, albuminuria of pregnancy, asthma, incontinence of urine,
gravel, cystitis, chronic lead poisoning, headache, neuralgia,
neurasthenia and lumbago, Hay fever, etc.”--(_Query in The Journal
A. M. A., Dec. 6, 1919._)
Venarsen
_To the Editor_:--The following is a copy of a letter sent to the
Intravenous Products Company, which needs no explanation:
June 8, 1917.
_The Intravenous Products Co., Denver, Colo._
Gentlemen:--In reply to your circular letter under date of June 3,
may I say that after using a great quantity of Venarsen both in
clinical and private cases, I can see no more effect upon these
cases than if so much water had been administered.
This is also the report of Don R. Black, pathologist for Bell
Memorial Hospital, University of Kansas. In our experiments all
bloods were tested before and after each administration of this
product.
William A. Wilson, M.D., Kansas City, Mo.
(_Correspondence in The Journal A. M. A., July 7, 1917._)
PART IV
CONTRIBUTIONS FROM THE JOURNAL: MISCELLANY
ALBERT ABRAMS, A.M., M.D., LL.D., F.R.M.S.
“Spondylotherapy,” “Electronic Reactions,” the “Oscilloclast,” the
“Electrobioscope,” Etc.
For some time _The Journal_ has received inquiries of which the
following recent examples are typical. This from an Ohio physician:
“Please give me some information concerning Dr. Abrams and his
diagnostic and therapeutic devices known as reflexaphore and
oscilloclast. If this is published please withhold my name.”
A physician in Massachusetts writes:
“Can you give me any information concerning Dr. (?) San Francisco,
California, who reports himself able to diagnose syphilis from a
drop of blood sent him on a blotting paper? He has caused a patient
of mine a great deal of needless worry.”
And from Rhode Island a physician facetiously inquires:
“I am interested to know of the ‘Reactions of Abrams.’ Have you any
information that you can give me in regard to this matter? They
apparently do wonderful things in the West.”
While a New York physician acknowledges his failure to keep up with the
times thus:
“To-day I had occasion to see a patient who mentioned having an
Abrams test for gonorrheal infection of the prostate. He also
stated he wished to have Abrams’ treatment for the same condition.
Could you enlighten me as to what these are? I thought I had kept
myself up to date as to all new tests and treatments in my line;
but evidently I have been delinquent.”
According to our records, Albert Abrams, A.M., M.D., LL.D., F.R.M.S.,
was born in San Francisco in 1864. He was graduated in medicine by the
University of Heidelberg, Germany, in 1882. Dr. Abrams is a member of
his local medical society and through that holds fellowship in the
American Medical Association. Dr. Abrams has written voluminously. In
1910, his book on “Spondylotherapy” (“Physio-Therapy of the Spine”) was
reviewed in _The Journal_. “Spondylotherapy” is a neologic creation of
Dr. Abrams. According to its disciples, it concerns itself “_only_ with
the excitation of the functional centers of the spinal cord” and has
been called “the science of evoking the reflexes of the body both to
diagnose and to cure disease.” In bringing its review of Abrams’ book
on “Spondylotherapy” to a close, _The Journal_ said:
“... one wonders whether this is an attempt to explain osteopathy
and chiropractic to the understanding of the regular practitioner,
or to exploit the very ingenious percussion devices of the
author, or whether it is really true that medical men really know
practically nothing about the cure of disease through treatment of
the spine. Let us hope that it is the latter and that a careful
study of this unique volume may open new avenues of therapy
heretofore undreamed of.”
While the review was obviously critical, yet in advertising the book,
the publisher picked out part of the closing sentence, omitted the
context, and quoted _The Journal_ as having said:
“Let us hope that a careful study of this unique volume may open
new avenues of therapy heretofore undreamed of.”
When this matter was brought to the attention of Dr. Abrams, he
replied, “I fail to see any real difference in the two quotations” and
“only one ... with an astigmatic mentality” could “see any incongruity
between the context and the concluding sentence.” Yet, in this same
letter which attempted to justify the garbling of a quotation so as
to make a critical review appear a laudatory one, Dr. Abrams declared
that the review in question was “conceived and executed in a malicious
spirit.”
Between 1912 and 1914 Dr. Abrams gave “clinical courses” on
“Spondylotherapy” in various parts of the country--price $50. These
“courses” were widely advertised by an Ohio concern that seems to make
a specialty not only of handling the advertising campaigns of those
members of the medical profession who have unusual or bizarre methods
to exploit, but also of acting as an agent for the sale of such devices
and publications as may be necessary to the proper practice of the
particular brand of therapy that is being exploited. At the time this
concern was featuring Abrams’ course it called attention to the alleged
fact that “no class were [_sic!_] so busy as those employing mechanical
treatment such as Osteopathy, Chiropractic, Mechanotherapy, etc.”
Says Dr. Abrams:
“Despite the fury of tongue or the truculence of the pen, the
osteopath and chiropractor are inspiring the confidence of the
community with their systems. Right or wrong in their theory, they
are, in vulgar parlance, ‘delivering the goods.’ Spondylotherapy
was a product of necessity--the translation of an ignored field of
medicine from a chaotic to a scientific basis.”
Possibly the following testimonial published by Dr. Abrams as typical
of many received, and credited to “Dr. Henry Stacy Dodge, Richmond,
Va.,” may explain the field that “Spondylotherapy” is to cover.
Incidentally “Dr.” Dodge is listed in the Richmond telephone directory
as a chiropractor:
“I have been in practice for fifteen years in Chiropractic and ten
years an Osteopath and I wish to say that during the last three
years I have received more genuine and sincere satisfaction from
the application of Spondylotherapy than all other methods combined.
My success in gastrology alone is worth many times the cost of the
information.”
More recently, Dr. Abrams has advertised that he gives a “course” in
Spondylotherapy in San Francisco, beginning on the first of each month.
The course last four weeks. “The honorarium for this course is $200.00.”
In 1912 an organization was created devoted to this new therapeutic
method: the “American Association for the Study of Spondylotherapy.”
Later Dr. Abrams was made Honorary President. Whether the organization
is still viable we do not know.
ELECTRONIC REACTIONS OF ABRAMS
In addition to “Spondylotherapy,” Dr. Abrams has also evolved what he
calls the “Electronic Reactions of Abrams.” These are said to make
possible long-distance diagnoses, it being necessary only to send a
few drops of blood taken from the patient and allowed to dry on a
slide. There are, it seems, certain instruments and devices used in
the performance of these diagnostic feats. By means of the “Electronic
Reactions” Dr. Abrams (while admitting the protective factor of
vaccination against smallpox) has discovered that practically all the
vaccines obtained from reliable firms yield the reaction (“electronic
tests”) of congenital syphilis, and that many of them also yield
the reaction of tuberculosis and of streptococci and staphylococci.
Further, “from the cicatrices of all vaccinated persons, one can
always elicit a reaction of congenital syphilis and in early scars a
tuberculous reaction.” Dr. Abrams also declares that exposing vaccine
virus for ten minutes to blue light will destroy the syphilitic,
streptococcic and staphylococci reactions and exposing it for the same
period to yellow light will destroy the tuberculous reaction.
One of Dr. Abrams’ disciples--Sir James Barr--frequently quoted with
evident satisfaction, declares that from a fresh sample of blood spread
over four square inches of white blotting paper, “Dr. Abrams can
diagnose the sex, race and disease of the patient.” However, there are
certain precautions that must be taken: The patient should face West,
“the blood should be taken in a subdued light and there should be no
strong red or yellow coloring material in the room.”
In various places Dr. Abrams has asseverated that “if
splancho-diagnosis is approached with a prejudiced mind, it is better
not to attempt it, for there are ‘none so blind as those that will not
see.’”
Dr. Abrams founded and edits _Physico-Clinical Medicine_. It is
published by “Physico-Clinical Co.” at 2135 Sacramento St., San
Francisco--the address, according to the telephone directory, of Dr.
Abrams’ residence. It is a quarterly “Devoted to the Study of the
Electronic Reactions of Abrams and the Visceral reflexes of Abrams, in
the Diagnosis, Treatment and Pathology of Disease.” Single copies, one
dollar; by the year, two dollars. The publication is, apparently, not
entered as second class matter, in fact, presumably, it could not be,
as it seems obviously to be an advertising affair. Each issue contains
material dealing with “Spondylotherapy,” “Splanchno-Diagnosis,”
“Electronic Reactions” and other discoveries and theories of Dr.
Abrams. In it also is published a list of “Some recent visitors at
Dr. Abrams’ laboratory,” the names and addresses of the “Lessees of
Oscilloclast” (about which more later), testimonials for Dr. Abrams,
etc.
Of course, it carries advertisements of Dr. Abrams’ “Physico-Clinical
Laboratory” (also at 2135 Sacramento St.) and his “Practical Courses
in Spondylotherapy and Electronic Diagnosis and Treatment” ($200 in
advance). Some of the devices of Dr. Abrams are also advertised. “No
apparatus sold on credit. Terms cash.” Among these are:
“Dr. Abrams’ Electrodes for Electronic Diagnosis $ 6.00
“Biodynamometer 36.00
“Dr. Abrams’ Reflex Set 36.00
“Dr. Abrams’ Electro-Concusser 120.00”
THE OSCILLOCLAST
But what seems to be the outstanding piece of apparatus, devised
or invented by Dr. Abrams, the pièce de resistance, as it were, of
physicoclinical diagnosis and treatment, is the “Oscilloclast.”
This device is not for sale. It can be had only on lease. The first
payment is $200 or $250, according to whether it is wired for
alternating or direct current. Then there is a monthly payment of
$5. Dr. Abrams publishes a list of more than 130 men who have leased
one or more “Oscilloclasts.” Sir James Barr’s name heads the list.
According to Dr. Abrams, the “Oscilloclast” owes its conception to the
therapeutic principles he advocates. These, in part, are:
“1. Physiologic phenomena are manifestations of electronic energy.
“2. Pathologic phenomena are manifestations of perturbed electronic
energy.
“3. The energy in health and disease has an invariable and definite
rate of vibration (determinable by the electronic reactions).
“4. Specific drugs possess a like vibratory rate as the diseases
for which they are effective.
“These like vibratory rates (hemovibrations) of drugs owe their
efficiency to their inherent radioactivity. Thus, an obsolete drug
like gamboge painted on the chest in incipient tuberculosis will
effect a symptomatic cure within a few weeks. Gamboge possesses
the same vibratory rate as tuberculosis. Our conception that
drug action is dependent on direct cellular contact is thus
demolished....
“5. All forms of energy whether derived from heat, electricity or
magnetism may be made to yield different rates of vibration and
these rates corresponding to the diseases are utilized for their
destruction.”
If one accepts one of Dr. Abrams’ theories, the possibilities of
such a piece of machinery as the “Oscilloclast” would seem to loom
large, not only in therapeutics, but also in economics. All one needs
to do, according to Dr. Abrams, is to ascertain “the vibration rate
of a drug” and then to substitute the same vibration as produced by
the “Oscilloclast.” Thus, if one substitutes the “vibratory rate of
atropin” for the drug itself “the mouth dries or the subject feels as
if it were puckered.” Conversely, if you switch the “Oscilloclast” to
the pilocarpin vibratory rate, there is a copious flow of saliva.
THERAPEUTIC RESULTS WITH OSCILLOCLAST
What some of the lessees of the oscilloclast are accomplishing (if we
are to believe the clinical reports published in _Physico-Clinical
Medicine_) may be gathered from the following quotations:
“Woman, Age 52.--Diagnosis of acquired syphilis made by one of our
most eminent clinicians. (?) Abrams test showed tuberculosis of the
apex of the right lung. No syphilis. Fourteen treatments with the
Oscilloclast at 5. Patient gained fourteen pounds in three weeks.
Now in perfect health.”
“Mechanic, Age 22.--Acute acquired syphilis. General eruption,
throat, mouth symptoms and chancre. Thirteen treatments with
the Oscilloclast at 3, and splenic sterilization only. Complete
abatement of all symptoms.”
“Woman, Age 42.--Strep infection of the second upper cuspid tooth
of three years’ standing. Well developed sinus. Regular discharge
of pus. Eight treatments with the Oscilloclast at 2. Clinically
cured.”
“Cancer of the pylorus and pylorectomy executed at the Mayo Clinic.
Later, vomiting, severe pains, loss in weight, etc. After the
third treatment [with “Oscilloclast”] pains ceased and, after 14
treatments, she was well and continued so when I last saw her.”
“Cancer of uterus. Inoperable. Severe uterine hemorrhages.
Electrode of Oscilloclast to cervix and hemorrhage ceased after
second treatment. After 14 treatments the patient declared she was
well. Another case of the same character was followed by equally
good results.”
ECONOMIC RESULTS WITH OSCILLOCLAST
It also seems to be a great business-getter, as the following
testimonials published by Dr. Abrams show:
“The Oscilloclast has doubled my business.”--S. King, M.D. (Pa.).
“I am doing good work with the Oscilloclast in T. B. and when I get
more room I shall want another machine.”--H. Michener (Kas.).
“We are swamped with work and our three cord Oscilloclast is
working to full capacity. We are still astonishing the incredulous
and keeping busy. We must have another Oscilloclast at once for
there are so many here who demand treatment.”--W. P. Myers, M.D.
(Cal.).
THE ELECTROBIOSCOPE
More recently, Dr. Abrams has extended his observations and
experiments, using what apparently is a modification of the old
fashioned pith ball suspended by a silk thread from a rubber rod with
which we all experimented during our high school days. This device
Dr. Abrams has called the “Electrobioscope.” It is for sale by the
Physico-Clinical Co. The “Electrobioscope,” in addition to doing
many other things, has demonstrated (to Dr. Abrams) the “sexuality
of numbers and sounds.” Thus, if the pith ball is charged negatively
and the numbers 1 to 9 are marked on a narrow board and the vowels
and consonants are marked on another board, it will be found--still
according to Dr. Abrams--that even numbers repel the pith ball while
odd numbers attract it. Vowels repel and consonants attract. “A female
hair repels and a male hair attracts.” From these data Dr. Abrams
deduces that “even numbers and vowels are female and odd numbers and
consonants are male.”
The value of music as a therapeutic agent is briefly touched on by
Dr. Abrams and we are told that the overture of “Tannhäuser” will
increase the pulse rate whereas “Meditation” diminishes blood pressure
and pulse rate. “In dogs, music augments elimination of carbonic acid
and increases the consumption of oxygen.” Love, says Dr. Abrams, “is
dependent upon matter in vibration and the passional component has a
wave metric index of 14 in both sexes.” In referring to legendary lore,
Dr. Abrams apparently assigns a scientific basis for the belief among
the bucolic that carrying around a potato has therapeutic virtue. Thus:
“A cut potato (carried on the person) prevents elicitation of the
stomach reflex when the negative pole of a bar-magnet is presented
to the stomach region whereas the positive pole will evoke dulness.”
It seems also that the “rheumatic rings” of iron “when worn yield a
neutral energy which prevents the elicitation of the stomach reflex
by either pole of a bar-magnet.” We learn, too, that the divining rod
“no longer belongs to occultism but is entitled to consideration as a
scientific fact.”
Dr. Abrams also has investigated methods whereby the sex of the fetus
may be diagnosed. In the human these investigations have, apparently,
been so limited as to permit only tentative conclusions. In the case of
eggs of the domestic fowl, Dr. Abrams reports that with four eggs that
yielded negative polarity, the result of incubation was four hens. Of
five eggs yielding a positive polarity only two hatched, one was a hen
and one a rooster, giving an “error in observation.” Three eggs tested
yielded neutral polarity and “as predicted the eggs were sterile.” In
case of an egg yielding a negative (female) polarity “an attempt was
made to reverse the sex by painting one end of the egg with a yellow
coloring material.” The result was a rooster.
Much more might be written about what one of our correspondents calls
the wonderful things they are doing in the West, but space forbids.
“Neither the fury of tongue,” says Dr. Abrams in the preface to his
book, New Concepts in Diagnosis and Treatment, “nor the truculence
of pen can discredit the author’s observations which are capable
of analyzation and demonstration.” If there is any scientific
foundation for the marvels that Dr. Abrams so picturesquely features,
the scientific world has not yet found it out!--(_From The Journal
A. M. A., March 25, 1922._)
Dr. Abrams’ Graduation
In this department of The Journal for March 25 appeared an article on
Dr. Albert Abrams and some of his discoveries. We have now received
a letter from a physician, who asks that his name be not published,
reading:
“_To the Editor_:--I notice in your article on Albert Abrams the
statement that he was born in 1864 and received his degree of M.D.
in Heidelberg 1882; if these data are furnished by himself and not
a typographical error--though I find the same data in the American
Medical Directory for 1916--then it is high time that some board of
censors should make a careful examination of his credentials.
“Anybody, like myself, who is acquainted with medical matters in
Germany knows that it is preposterous to assume that anybody could
obtain the degree of M.D. in any German university at the age of 18
years.
M. D., Leipzig.”
Eighteen _is_ rather young to receive an M.D. degree from Heidelberg!
By again going over the various sources of information available the
following data were collected: In Polk’s Medical Directory for 1886 Dr.
Abrams’ name appears as a graduate of the University of Heidelberg,
1882, and of Cooper Medical College in 1883. The records we have
from these two institutions confirm these dates. The year of Dr.
Abrams’ birth seems less clear. In the early part of 1902 the American
Medical Association sent Dr. Abrams a blank for him to fill out for a
permanent record. This was returned in due course and, according to
it, Dr. Abrams was born in San Francisco Dec. 8, 1863. This same date
appears in various editions of “Who’s Who in America.” A blank sent by
the A. M. A. Directory Department to Dr. Abrams in 1908 asking for a
personal biographical report was returned Aug. 20, 1908; it gave Dr.
Abrams’ date of birth as Dec. 8, 1864. A similar blank sent in the
earlier part of 1909 was returned giving the same birth date. We learn,
however, that an affidavit executed in 1917 states that Albert Abrams
was born in San Francisco Dec. 8, 1862.
Just how long Dr. Abrams attended Heidelberg University before he was
granted the M.D. degree, we do not know. Apparently, at that time the
standards for admission to that institution were not especially severe
and the length of time one would have to attend before being admitted
to an examination seems to have depended on the educational credentials
that the matriculant offered. What credentials Dr. Abrams submitted,
we do not know. Assuming that the earliest date (1862) represents Dr.
Abrams’ date of birth, he could have been but twenty years old when
he received his M.D. from Heidelberg. This indicates a precocity that
might have forecast Dr. Abrams’ later achievements.
Throughout the records of Dr. Abrams’ educational credentials there
appears the statement that he also graduated from the “University
of Portland” in 1892, receiving the degree of A.M. From references
available we have been unable to find any record of a “University of
Portland.”--(_From The Journal A. M. A., April 8, 1922._)
A Defense by Upton Sinclair
A somewhat voluminous letter has been received from Mr. Upton Sinclair,
which is a defense of Dr. Albert Abrams of San Francisco. We publish
Mr. Sinclair’s letter because we believe it is written in honesty and
sincerity--and because The Journal readers will enjoy it! It is worth
mentioning in this connection that Mr. Sinclair in his latest book
devotes a few pages to a eulogy of Dr. Abrams and his methods. This
material has not only been reproduced by Dr. Abrams in his “house
organ” _Physico-Clinical Medicine_ but is reprinted in leaflet form and
is being distributed by some of the individuals who are exploiting the
Abrams methods. Such reprints have been sent to this office by both
laymen and physicians.
MR. SINCLAIR’S LETTER
_To the Editor._--A few weeks ago you published an article dealing
with the discoveries or claims of Dr. Albert Abrams of San Francisco.
I happen to be attending Dr. Abrams’ clinic at the time and have
discussed this article with him at some length. Dr. Abrams follows the
policy of ignoring attacks on his work, taking the view that in the
long run, the man who cures disease makes his way in the world in spite
of all opposition. However, it is easy to see that he has been deeply
hurt by this attack on his reputation, and as one of his friends and
most ardent admirers I am taking the liberty of addressing a letter to
you.
I do not know if the rules of your publication permit intervention
in medical affairs by a mere layman. Permit me to introduce myself
as a layman who for some twenty years tried faithfully to be cured
of various diseases by many doctors of the best reputation in many
parts of the world, and failed; and who, therefore, was compelled, as
a matter of self-protection, to look into the question of health for
himself. I have read so many different kinds of books on health and
made so many experiments of my own that nowadays when I meet with a
group of physicians I find that before long they come to accept me as
one of themselves. You may not go that far, but at least you may be so
generous as to allow me to tell you a little of what I have seen during
the time I have spent in the clinic of Dr. Albert Abrams.
I observe that in the course of your two page article dealing with this
subject, you nowhere have anything to charge against Dr. Abrams, nor
do you show that you have investigated his work. You consider that all
you have to do is to quote Dr. Abrams’ own words as to what he can do,
and that _these words refute themselves_. [Italics our.--Ed.]. Also you
quote Dr. Abrams’ schedules of prices, and imply that his motives are
mercenary. I will take up these two questions one at a time.
WHAT DR. ABRAMS CAN DO
First, as to what Dr. Abrams can do: I have been here and have seen
him do all that he claims to do. Therefore, you will understand that
this portion of your argument does not produce much impression on me. I
merely say to you, why do you not come and see, or why do you not send
some reliable representative to see--before you take it for granted
that Abrams is a knave or a lunatic? This man is not merely a colleague
of yours; he is a fellow of the Royal Medical Society of Great Britain
[We know of no such society.--Ed.] and surely he was entitled to a
little elementary courtesy from you. Why did you not at least write
to him and permit him to put before you a little of his evidence on
the genuineness of his work? You admit that he is a graduate of the
Universities of Heidelberg and Stanford; [Dr. Abrams is not a graduate
of “Stanford.”--Ed.] you admit that he was graduated from Heidelberg at
the age of twenty. It happens that this was the youngest and remains
the youngest age at which any man has taken a Doctor’s Degree at that
University in a hundred years. If you had inquired further you might
have learned that ten years ago Abrams was one of the most respected
physicians in San Francisco. What has he done since to forfeit the
honors of a lifetime? All that he has done is to shut himself up in his
laboratory and make the most revolutionary discoveries of this or any
other age; and now when he emerges and offers this work to the world,
you can think of nothing to do but jeer at him.
I spent two weeks in his clinic; then I took six months to write to
his physicians all over the country, _and to experiment with his
cures on a great number of my friends_. [Italics again ours.--Ed.]
Now I am spending another two weeks in his clinic, and I venture to
stake whatever reputation I have, or hope to have in this world, upon
the statement that Albert Abrams has discovered the great secret of
the _diagnosis and cure of all the major disease_. [Again we must
italicize.--Ed.] He has proven by diagnosing with the taps of his
own sensitive finger tips over 15,000 people, and my investigation
convinces me that he has cured over 95 per cent. of these who have
taken his treatments. Moreover, he has taught his method to 200 or 300
other physicians, and some 80 per cent. of these have submitted to me
answers to a questionnaire in which they claim thousands of cures.
You may say, perhaps, that I am not competent to judge of cures.
For the sake of argument, I will grant that; but I assert that I am
competent to judge of physicians, for I have tested several score of
them, and if I ever knew a devoted scientist and a great humanitarian,
it is Albert Abrams. In his clinic I have met perhaps a hundred
physicians, and I venture to assert that a number of these are men
both of integrity and capacity, and when I asked them why they came, I
got invariably one answer: “Because I sent him blood specimens and I
found that invariably he sent me a correct diagnosis.” Not once, but at
least two score times, I have seen Albert Abrams take a blood specimen
brought to him, without even the name of the patient, and heard him
diagnose cancer or sarcoma, and from the blood specimen locate the
growth PRECISELY TO AN INCH. [Italics fail one here!--Ed.] Then I have
seen the patient, an entire stranger to Abrams, brought into the clinic
and examined, not merely by Abrams, but by a score of other physicians,
and the growth found precisely at the spot indicated. (This was done
twice between the time when this letter was dictated and the time when
it was transcribed.) Three times, yesterday, I saw a diagnosis made of
syphilis and the patient brought in, and all the standard reactions
demonstrated. I have seen, not once, but hundreds of times, tubercular
lesions diagnosed and located from the blood specimen and the patient
brought in and the condition demonstrated by percussion. All these
things are going on day after day. They are being done in other
clinics in several score of cities, and you may have the addresses for
the asking. Why do you not ask? [We have some such addresses in the
Propaganda files.--Ed.]
THE ECONOMIC ELEMENT
I take up the second criticism, that Albert Abrams is mercenary. He
charges $200.00 for the clinical course, which may last as long as
the physician wishes. It seems to me that that price is to be judged
somewhat in relation to what he has to teach. He maintains a large
establishment; he has need of many assistants, and expensive apparatus
for his research work. He charges for the use of his oscilloclast a
deposit of $250.00, and a rental of $5.00 per month. The former item
covers the cost of manufacturing the machine, and the second item must
be compared with the fact that a great number of physicians who are
using this instruments are today _enjoying incomes of from $1,000.00
to $2,000.00 per week_. [Once more, italics!--Ed.]
A few weeks ago I visited a physician who told me he had treated
thirty-two patients that day with his one instrument, and that his
income was over $1,300.00 for that week, and I could name several who
have given similar accounts. It may be, of course, that you will say
they should not charge so much. The average charge is about $200.00 for
a _guaranteed cure of such diseases as syphilis, tuberculosis, cancer
and sarcoma_. [Italics our again.--Ed.]. Do you know anyone who will
guarantee to cure a cancer or sarcoma at any price? [No!--Ed.]
I am sure you will agree with me that it would be possible to find
physicians who would be willing to put up many hundreds of dollars to
guarantee that neither cancer nor sarcoma can at the present time be
cured except by operation. And I can recall many cases in my lifetime
when I paid hundreds and even thousands of dollars to be cured of
diseases by the medical profession, and I am unable to recall a single
case where I was ever cured of anything. [Still this need not be an
indictment of scientific medicine.--Ed.]
Finally, as regards to the subject of mercenary motives, permit
me to state that I have in my possession a letter from Dr. Abrams
stating that what he desires is to have established an institute for
the purpose of making his work known to the world, and that if such
an institute is established he is prepared to give up all his other
work and devote all his time, without compensation, to the institute.
Furthermore, he is willing to furnish his instruments without charge to
any medical institution which requests them. Within the last few days,
on account of the enormous number of blood specimens brought into his
clinic, Dr. Abrams has signed in my presence, and is prepared to issue
a statement to the effect that his charge for examining blood specimens
is to be raised from $10.00 to $25.00 and all checks are to be made
payable to a Trust Fund which is to be immediately established, for the
purpose of founding the institution above referred to. I do not see how
the medical profession can ask for more than this; but if you do, I
should be pleased to receive your suggestions and transmit them to my
friend.
AN OLD STORY
Now, this failure to recognize a great medical discovery is an old
story. It was the experience of Harvey [We knew poor Harvey would be
dragged into this.--Ed.], of Jenner and of Lister. But the world moves
on, and men’s brains should improve, and it should be possible to
shorten the time of persecution which the great pioneers of science
have to suffer. I put to you this simple proposition: Send a reliable
man of science to the clinic of Albert Abrams, and let him stay there
as long as he pleases and see all that he wishes to see, and then send
you a report, and if it indicates that you have blundered in your
condemnation, be honest and say so, and save your profession from
another black mark against its name.
Upton Sinclair, Pasadena, Cal.
Comment
A testimonial is of value to the extent that the person giving it
is an authority on the subject on which he testifies. When Mr.
Sinclair testifies on socialism we may listen respectfully, believing
him competent to express an opinion; but when Mr. Sinclair gives a
testimonial on certain bizarre methods of interpreting difficult and
obscure problems in medicine, he leaves us cold.
Mr. Sinclair says that he has spent time in Dr. Abrams’ clinic and is
wonderfully impressed with Dr. Abrams’ achievements. So is the small
boy impressed with the marvelous facility with which the magician
extracts the white rabbit from the silk hat. Mr. Sinclair is convinced
“that Albert Abrams has discovered the great secret of the diagnosis
and cure of all the major diseases.” The small boy is equally convinced
that the prestidigitator has solved the mystery of producing snow white
bunnies from airy nothings.
Great store seems to be placed by Mr. Sinclair on the favorable
reports that he obtained from those who are relieving the public--of
from $1,000 to $2,000 a week--by the Abrams methods of diagnosis
and treatment. What kind of evidence did he expect to get from such
obviously _ex parte_ sources? Mr. Sinclair’s naïveté may be childlike,
but it is not scientific. While the significance of the statement may
not be apparent to Mr. Sinclair, it is a fact that when the names of
the one hundred or more lessees of the Abrams “Oscilloclast” were
checked up it was found that a number of these individuals were already
in the Propaganda files in some other connection. That these disciples
of Abrams, who are “enjoying incomes of from $1,000 to $2,000 a week,”
should speak favorably of the Abrams method was inevitable!
Some years ago Upton Sinclair wrote a book on his (at that time)
panacea for human ailments. It was the “Fasting Cure.” At that time
he told of individual acquaintances suffering from various ailments:
one was “dying of kidney trouble”; another was “in the hospital from
nervous breakdown”; still another had “only a year to live,” while a
fourth was “a nervous wreck, craving for death.” Of these Mr. Sinclair
said at the time: “And there is not one of these people whom I could
not cure if I had him alone for a couple of weeks.”
MR. SINCLAIR AND THE MEDICAL PROFESSION
At that time Mr. Sinclair was greatly perturbed at the attitude of
the medical profession toward his dictum that “the fast is Nature’s
remedy for all diseases.” There was just one physician “who was really
interested.” This man lived “in an out of the way town in Arkansas” and
asked Sinclair to “let him print several thousand copies of the article
in the form of a pamphlet to be distributed among his patients.” As
Mr. Sinclair said at the time, “one single mind among all the 140,000
[physicians], open to a new truth!” And this “open mind,” that of a
man who was practicing in a small town in Arkansas and needed “several
thousand copies” of the Sinclair article to distribute to his patients!
After his “fasting cure” experience, Mr. Sinclair had the “raw food”
fad--also abandoned in due time. In one of his recent books (“The Brass
Check”) he refers to his outgrown fads in the following words: “I ...
was willing to try anything in the hope of solving the health problem,
which I have since realized is insolvable--there being no diet or
system of any sort which will permit a man to overwork with impunity.”
He states further in this same connection:
“I look back in retrospect and have not a little fun over my ‘monkey
diet’ days.”
Who shall say that ten years hence Mr. Sinclair may not be able to
look back, good humoredly, in retrospect, to another time when he was
“monkeying” with a subject that was beyond his ken?--(_From The Journal
A. M. A., April 29, 1922.)_
ACETYLSALICYLIC ACID, NOT ASPIRIN
The Council on Pharmacy and Chemistry publishes a report in this
issue giving its reasons for deleting “Aspirin-Bayer” from New and
Nonofficial Remedies. In order that a standard may be provided, the
drug acetylsalicylic is retained[259] in N. N. R. under its scientific
name, acetylsalicylic acid, aspirin appearing as a synonym. The
attempt on the part of the Bayer Company to perpetuate the monopoly it
has had for seventeen years in the United States was briefly discussed
editorially in The Journal, Aug. 12, 1916. We quoted from _Printers’
Ink_, a magazine devoted to advertising, in part as follows:
[259] See index for additional article.
“The manufacturers of aspirin are about to launch an extensive
advertising campaign to clinch the market as far as possible before
the expiration of their patent rights next year.... The purpose
of the campaign is to identify the product with the trademark of
the Bayer Company and to this extent hamper competition after the
expiration of the patent.”
It is worth while reminding physicians of the privileges the Bayer
Company has enjoyed for so many years, owing largely to our inequitable
and crude patent laws, or to their construction. First, it should be
remembered that practically no other country in the world, not even
the original home of the preparation, would grant a patent on either
acetylsalicylic acid, the product, or on the process for making that
product. The United States granted both! As a result, for seventeen
years it has been impossible in this country for anybody except the
Bayer Company to manufacture or sell acetylsalicylic acid, either under
its chemical name or under any other name. Neither was it possible for
individuals, hospitals or any other institutions to import it, legally,
for their own use.
Needless to say, the American people have been made to pay exorbitantly
for the monopoly our patent office granted this firm. Three or
four years ago The Journal, through the American consuls, obtained
information regarding the price at which acetylsalicylic acid was sold
in foreign countries. At that time, acetylsalicylic acid, as “aspirin,”
was costing American druggists--and of course the American public had
to pay still more for it--43 cents an ounce. Just across the border
in Canada it sold for one-third the price asked here. In some of the
foreign countries, acetylsalicylic acid under its scientific name could
be purchased by the druggists of those countries at from one-sixth to
less than one-tenth the price that it cost American druggists. Here are
some of the figures:
Austria-Hungary 4 cents an ounce Holland 4 cents an ounce
British Isles 6 cents an ounce Norway 4 cents an ounce
Denmark 4 cents an ounce Sweden 4 cents an ounce
France 4 cents an ounce United States 43 cents an ounce
Germany 4 cents an ounce
Not content with the iron-bound monopoly which it had been granted
through our patent laws, the company attempted further to clinch its
exclusive rights by giving the preparation a fancy name, “aspirin,” and
getting a trademark on this name. The patent on acetylsalicylic acid
expires next month (February, 1917). After its expiration the product,
and its method of manufacture, become common property. American
manufacturers will now be able to do what manufacturers in other
countries, other than the patentees, have long been doing--make and
sell acetylsalicylic acid.[260]
[260] The Bayer people may try to convey the impression that
“Aspirin” is pure and reliable whereas other brands are not. Since
acetylsalicylic acid is a definite chemical compound, there is
no more likelihood of this being sophisticated than there is of
quinin being adulterated. Furthermore, the Council in accepting
acetylsalicylic acid for New and Nonofficial Remedies has provided
standards of purity which will insure a uniform product. The brand of
one firm--Powers-Weightman-Rosengarten Co., of Philadelphia--has been
accepted by the Council on Pharmacy and Chemistry for inclusion in New
and Nonofficial Remedies, 1917.
Unfortunately, it is extremely improbable that any American
manufacturer will market acetylsalicylic acid under the name aspirin,
although we believe they would have a legal right to do so. The courts
have held in related instances that when a patented article has been
known during the life of the patent under a trademarked name, with
the expiration of the patent the name as well as the product becomes
common property. The classical “Singer Sewing Machine” decision and
the lanolin case are in point. The Bayer Company, through a widespread
newspaper advertising campaign, seems to be attempting to perpetuate
its seventeen-year monopoly by leading the public to believe that
there can be only one brand of genuine acetylsalicylic acid on the
market--that made by the Bayer Company.
The firm will, of course, continue to manufacture and advertise the
product under the name “Aspirin-Bayer,” and will probably charge high
prices for it, as was the case with phenacetin (acetphenetidin). In
any event, physicians hereafter should do what for a long time we have
been advising should be done, namely, prescribe the compound under
its scientific name, acetylsalicylic acid. They should do this if for
no other reason than that they would be using the name which carries
with it a reminder of the composition of the preparation. Of course,
for those who have been writing “aspirin” it will be rather difficult
to write “acetylsalicylic acid,” just as a quarter of a century ago
it was difficult for the physician of that day who had been using
the copyright name “antifebrin” to write “acet-anilid,” a name which
nowadays is easy, even for laymen.--(_Editorial from The Journal
A. M. A., Jan. 20, 1917._)
“What’s in a Name?”
Under the caption “What’s in a Name?” the current (April) issue
of the _Journal of Industrial and Engineering Chemistry_ has an
editorial dealing with the nomenclatures--common and proprietary--of
acetylsalicylic acid. The editorial was prompted by an article by Dr.
Leech printed in the same issue. Replying to its own question:
“The answer to this question so far as it applies to
acetylsalicylic acid (popularly known as aspirin) is the difference
between eighty-eight cents, the price the druggist must pay for
every one hundred tablets of Bayer aspirin, and forty cents,
the cost of an equally pure American product. Naturally, this
difference in cost is passed on to the individual consumer.
“That no scientific justification exists for this difference in
cost is clearly shown in the contribution by Dr. Paul Nicholas
Leech, of the Chemical Laboratory of the American Medical
Association, page 288 of this issue.
“On the other hand, the excess profit fully warrants the extensive
and shrewdly-worded advertising campaign now in progress, a
campaign which must eventually fail, because in the first place,
it is contrary to the prevailing spirit of modern advertising, the
motive of which is constructive rather than destructive, and, in
the second place, it appeals merely to the temporary ignorance of
the public at large, and has no basis in fact.
“We have been informed that the Custodian of Alien Enemy Property
has taken charge of the stock interests of alien enemies in the
company conducting this propaganda. Surely the Custodian will not
care, even in a trustee capacity, to continue as a participant in
a misleading campaign whose sole purpose is the perpetuation of a
monopoly hitherto enjoyed under full patent protection.”
The article to which the editorial refers is a somewhat technical one
giving the findings of an examination made, at the request of the
Council on Pharmacy and Chemistry, in the Chemical Laboratory of the
American Medical Association by Paul Nicholas Leech, Ph.D., of various
American brands of acetylsalicylic acid (aspirin). The result of the
investigation may be summed up briefly in the statement that there
are on the American market, made by American firms, several brands of
acetylsalicylic acid that are just as good as, if not better than, the
Bayer product.
The Journal has called attention to the misleading propaganda on the
part of the Bayer Company (Farbenfabriken vorm. Friedr. Bayer & Co.),
in its attempt to perpetuate the monopoly granted under our inequitable
patent laws. This is done by conveying the inference that the only pure
acetylsalicylic acid on the market is that known as “Aspirin-Bayer.”
Physicians should again be reminded of the facts in the case of
aspirin: Practically no other country in the world, and certainly not
Germany, the original home of aspirin, would grant a patent either
on acetylsalicylic acid, itself, or the process for making it. The
United States granted both! As a result no one in this country except
the Bayer Company could for seventeen years manufacture or sell
acetylsalicylic acid either under its chemical name or under any other
name. Nor was it permissible for hospitals or individuals to import it.
While the monopoly held, the American people were compelled to pay from
six to ten times as much for acetylsalicylic acid as were the people
of Great Britain, France, Germany, Austria-Hungary, Denmark, Holland,
Norway or Sweden. At a time when American druggists were compelled to
pay 43 cents an ounce for acetylsalicylic acid as aspirin, just across
the border in Canada it sold for about one-third the price.
About a year ago, the Council on Pharmacy and Chemistry announced that
“Aspirin-Bayer” had been deleted from New and Nonofficial Remedies
while the scientific term acetylsalicylic acid was retained along with
standards to insure its quality. The necessity for a standard becomes
evident when it is remembered that acetylsalicylic acid is not yet an
official drug, and its purity, therefore, is not subject to the control
of the federal Food and Drugs Act. It is worth while at this time to
remind physicians that several brands of acetylsalicylic acid (aspirin)
have been found to comply with the standards set by the Council on
Pharmacy and Chemistry and have been admitted to New and Nonofficial
Remedies.[261] These, of course, are thereby subject to the control of
the federal law to conform to the standard to which they profess.
[261] The following brands of acetylsalicylic acid conform to the
standards of the Council and are in New and Nonofficial Remedies:
“Aspirin--
L. and F.”: Lehn & Fink, New York.
“Acetylsalicylic Acid--
Squibb”: E. R. Squibb & Sons, New York.
“Acetylsalicylic Acid--
Merck”: Merck & Co., New York.
“Acetylsalicylic Acid--
Milliken”: John T. Milliken & Co., St. Louis.
“Acetylsalicylic Acid--
M. C. W.”: Mallinckrodt Chemical Works, St. Louis.
“Acetylsalicylic Acid--
Monsanto”: Monsanto Chemical Works, St. Louis.
“Acetylsalicylic Acid--
P. W. R.”: Powers-Weightman-Rosengarten Company, Philadelphia.
Leech’s report gives still greater weight to the suggestion that
has been made for some time, viz., that physicians should describe
acetylsalicylic acid under its scientific name rather than its
proprietary name, even though, in the opinion of The Journal, the
proprietary name, aspirin, has become common property since the
expiration of the acetylsalicylic acid patent. Every consideration
of public interest, of patriotism and of ordinary common sense
should prompt physicians to specify acetylsalicylic acid in writing
prescriptions.--(_Editorial from The Journal A. M. A., April 13, 1918._)
Advertising Principles--Lay and Medical
The Journal has received two letters, one from a physician who had
written to the New York _Tribune_ protesting against an advertisement
of “Aspirin (Bayer)” that appeared in the rotogravure supplement of a
Sunday edition and the other the New York _Tribune’s_ answer to the
protest. The two letters make an editorial in themselves. Here is the
letter of the physician--Dr. Edwin H. Shepard of Syracuse, N. Y.--which
was addressed to the editor of The Journal:
“When a great daily newspaper takes a stand for honest advertising
it seems worthy that acknowledgement should be made. On April 14 the
illustrated Sunday supplement of the New York _Tribune_, together
with many of the other papers of the country, published a duplicate
of the enclosed advertisement of ‘Aspirin.’ Your own instructive
editorial on ‘Acetylsalicylic Acid, or What’s in a Name?’ had
appeared in the copy of The Journal of the day preceding.
“Believing in the sincerity of the _Tribune_ in its effort for honest
advertising, I sent them a copy of your editorial together with the
page of advertisement, also calling attention to the statements in
the advertisement which seemed questionable. Among the questionable
matters in the advertisement were the statements, ‘The one genuine
Aspirin,’ ‘No other is genuine,’ ‘That which is genuine possesses
qualities of excellence never found in imitations,’ ‘For your
protection ... every package and tablet is marked with the Bayer
cross,’ ‘Your guarantee of purity,’ and ‘Refuse substitutes as they
may prove ineffective and harmful.’
“The Tribune was requested to investigate into the standing of the
Bayer company and its product. A few days later the enclosed letter
was received from the paper’s Bureau of Investigations.”
And here is the New York _Tribune’s_ answer, signed by R. R. Baer,
assistant director of that paper’s Bureau of Investigations:
“We have your letter of April 14th, which was acknowledged on
the 22nd, in re Aspirin. For your information: Our rotogravure
supplement is printed a number of days in advance of the Sunday
paper. When these copies which have already been printed are used,
no further Aspirin copy will appear. This means a loss of some four
pages.”
How many of the numerous medical journals that are still carrying the
“Aspirin (Bayer)” advertising would make such a financial sacrifice for
mere principle?--(_From The Journal A. M. A., May 25, 1918._)
“Aspirin”--A Common Name
“Aspirin” as a trademark will no longer exist if the recommendation
of the Examiner of Interferences of the United States Patent Office
is upheld, as it probably would be, should the matter be taken to the
courts. The opinion of the Patent Office was the result of a petition
by the United Drug Company in the case of that company against the
Bayer Company, or, as it was called at the time the suit was brought,
the Farbenfabriken of Elberfeld Company. The stand taken by the Patent
Office is directly in line with that that has been held in this and
other cases by The Journal, which has for years insisted that it was
against public policy to permit patentees to extend the seventeen-year
monopoly, which the patent laws grant, to a perpetual monopoly by
the simple device of obtaining a trademark for the name of the thing
patented. It is a fundamental principle in law that “no one can have a
monopoly in the name of anything.” This, of course, has been recognized
and admitted even by those manufacturers who have attempted to invoke
the trademark laws to obtain an unwarranted advantage.
The manufacturers of aspirin have held that the chemical name
“monoaceticacidester of salicylic acid” was the true name of the
patented article, and was the _only_ name which became public property
when the patent right expired. The Patent Office points out, however,
that for years the only name that the public ever saw on the brand
of monoaceticacidester of salicylic acid made by the holders of the
patent on this product was “Aspirin.” The Examiner of Interferences
in his decision points out that, previous to 1915, the Bayer Company
sold no tablets to the retail-purchasing public, but marketed its
product as a powder; further, that it did sell vast quantities of the
powder to tablet-makers, who sold “Aspirin Tablets,” and that the
consuming public knew the product only by the name “Aspirin.” This
name, then, had a significance to the purchaser, similar to that of the
word “quinin” on a package of quinin tablets, or the word “calomel”
on a package of calomel tablets. As the Patent Office says: “In other
words, the _prima facie_ significance of this word ‘Aspirin’ to such
purchasers was that of a name”--and as a name it is “necessarily
incapable of exclusive use by any one.”
The Patent Office’s decision also brings out the fact that, until the
owners of the aspirin patent commenced making tablets themselves, the
aspirin tablets on the market were not uniform, and that this lack of
uniformity was a fraud on the public which the owners of the aspirin
patent should have prevented. The concern did prevent it when it began
to make the tablets itself, but maintained in its contention against
the United Drug Company that it was unable to control the matter
previously--a contention to which the Patent Office gives short shrift.
It is further pointed out that the Bayer Company evidently recognized
the weakness of its contention by the emphasis it placed through its
advertising on the “Bayer Cross.”
When the Bayer Company began manufacturing its own aspirin tablets,
it made a pretense of complying with the letter of the law, while
violating its spirit, by placing on the label under the word “Aspirin,”
the statement that “the monoaceticacidester of salicylic acid in these
tablets is the reliable Bayer manufacture.” Says the Patent Office:
“With regard to the expression ‘monoaceticacidester of salicylic
acid,’ a mere inspection of it is sufficient to apprise any one of its
inherent unsuitability for use as a name by the lay purchasing public.”
This attempt on the part of the company to “beat the devil around
a stump” tended, in the opinion of the Patent Office decision, “to
show that the respondent was familiar with the methods of some modern
traders to meet the trend of the law.” And, discussing such methods,
the Examiner of Interferences says: “A very popular one is for a trader
to seemingly bend to the necessity of the situation by placing on the
label a notation which in theory, but not in practice, may be used by
the public to identify the article after the monopoly has expired. To
the examiner this practice seems to be merely a manifestation of that
keen commercial instinct which endeavors to keep just ahead of the law.
This instinct is fairly common in traders, and is clearly disclosed in
trademark infringement cases.”
Summed up, the decision is to the effect that, as in any case prior
to 1915, the public had been driven to look on the word “Aspirin”
as the name of a _thing_, and as the Bayer Company had not used the
word as a “trademark” within the meaning of the law, the Patent
Office recommends that the registration of “Aspirin” as a trademark
be canceled. If no appeal is taken from this decision, or in case
an appeal is taken, should the opinion be sustained, the attempt on
the part of the patentees of aspirin to get a perpetual monopoly on
their product through the trademark laws will have been definitely
defeated.--(_Editorial from The Journal A. M. A., Jan. 11, 1919._)
“Aspirin Bayer” and the Sterling Products Company
A correspondent, who asks that his name be not published, writes:
“Your editorial on ‘Aspirin or Acetylsalicylic Acid--An Important Court
Decision’ is timely. Too often, I fear, physicians forget ‘what’s in
a name.’ I have been told that the Sterling Products Co., the present
owners of the Aspirin-Bayer rights, are manufacturers of other ‘patent
medicines.’ Are they interested in the Winthrop Chemical Company, which
firm seems to be using the much vaunted ‘Bayer Cross’ on the labels of
the products formerly imported from Germany by ‘The Bayer Company’? If
you answer this in The Journal, kindly omit my name.”
The recent history of Bayer & Co., is somewhat as follows: Shortly
after the United States entered the war, the Alien Property Custodian
took over the property of Bayer & Co. (Inc.) and its subsidiary, the
Synthetic Patents Co. In his report to congress the Custodian said:
“The stock of Bayer & Co. (Inc.) and of Synthetic Patents Co.
was sold by me at public auction, the successful bidder being
the Sterling Products Co., a West Virginia corporation dealing
in proprietary medicines. This company had previously agreed to
dispose of the dye plant and patents, in case it secured the
property, to Grasselli Chemical Co., one of the largest makers of
heavy chemicals in the country. The price paid was $5,310,000, plus
back taxes and other obligations of many hundred thousands more.”
After the Sterling Products Company had acquired the pharmaceutical
end of the business, the Winthrop Chemical Co. was incorporated in
the state of New York. This concern seemingly secured control of all
the Bayer pharmaceutical specialties except “Aspirin.” The Bayer
Co., it was announced, had been merged with the Sterling Products
Co., and “Aspirin-Bayer” added to the latter firm’s list of “patent
medicines”: Cascarets, Danderine, Pape’s Diapepsin, California Syrup of
Figs, Neuralgine and Dodson’s Livertone. The business is apparently a
paying one financially as witness the following excerpt from a recent
announcement in a drug journal:
“Stockholders of the Sterling Products Co., Inc., of Wheeling,
manufacturers of Neuralgine, Cascarets, Bayer’s Aspirin, and
other well known products, and the largest proprietary medicine
organization in the world, at their annual meeting received a
report of Manager W. E. Weiss, which showed that the company did
a $10,000,000 business in 1920. The total profits were $2,100,000,
while a total of $1,080,000 was paid out in dividends.”
Just what relationship exists between the Winthrop Chemical Co., and
the Sterling Products Co., we do not know. As our correspondent points
out, the “Bayer Cross” is used on the label of the Winthrop products.
The advertising campaign of “Aspirin, Bayer” since it entered the
“patent medicine” field has been typical of that field. By half truths
and inferential falsehoods the public has been led to believe that the
only genuine aspirin on the market is that put out under the Bayer
name. The facts are, of course, that the aspirin of any reputable firm
is just as good as the aspirin put out by the makers of Livertone,
Danderine and Cascarets.
There is one point, however, that is of vital importance to the medical
profession; The decision recently rendered in the United States
District Court of Southern New York makes it obligatory for druggists,
when filling a physician’s prescription calling for “aspirin,” to
dispense the Bayer product. When the public buys aspirin on its own
responsibility--without specifying any particular brand--the druggist
may give the purchaser any make of acetylsalicylic acid he sees fit. To
repeat what was said in The Journal’s comment on this decision: “Unless
a physician wishes to cater to the concern owning the Bayer rights and
to aid in perpetuating what was a monopoly for seventeen years, he
should be careful to prescribe the drug under the term ‘acetylsalicylic
acid,’ The court now places the responsibility directly on the medical
profession. Avoid ‘aspirin’--write ‘acetylsalicylic acid.’--(_From The
Journal A. M. A., June 11, 1921._)
THE ALLIED MEDICAL ASSOCIATIONS OF AMERICA
Another Rocket in the Pyrotechnics of Quasimedical Organizations
It was once said, in the days when diploma mills flourished, that
it seemed easier to start a “university” than it was to open a grog
shop. A study of quasimedical organizations convinces one that it is
easier to found a “medical society” than it is to establish a peanut
stand. Most reputable practitioners of medicine who care to affiliate
themselves with medical organizations are members of the American
Medical Association, its component societies, or similar scientific
bodies. It is not surprising then, that those who live and move in
the twilight zone of professionalism, from visionaries riding bizarre
medical hobbies to those who have special interests to exploit, should
create and make use of hybrid medical organizations. Such organizations
multiply as rapidly as rabbits. They flourish for a while, obtain more
or less newspaper and other publicity--usually more, because of the
sensational methods of those controlling them--then, having served the
purpose of those who brought them into being, they lapse into innocuous
desuetude.
The official accouchement of the Allied Medical Associations of America
occurred, according to that organization’s report, May 18, 1918. On
the official stationery of the Allied Medical Associations of America
in use in May, 1919, we find the names of the “Officers,” “Censors,”
etc. These constitute, presumably, the more prominent members of this
organization. We give briefly, some data regarding some of these so
that a rational perspective may be obtained:
L. M. Ottofy, M.D., St. Louis, Mo.--Dr. Ottofy seems to have been
the chief organizer, if not, indeed, the founder. He has been its
“Secretary-Treasurer” since its inception; he is also “editor” of
its journal. Ottofy, according to our records, was born in 1865 at
Budapest, Hungary, and was graduated in 1888 by the Homeopathic Medical
College of Missouri. In Polk’s Medical Directories for 1914 and 1917,
Ottofy has those extended notices which any physician can obtain who
cares to pay for them. According to these notices, Ottofy is, or has
been, affiliated with the following “societies”:
President of the International Cancer Research Society.
Ex-President of the St. Louis Society of Medical Research.
Second Vice President of the Missouri Institute of Homeopathy.
General Secretary of the American Association of Progressive
Medicine.
Chairman of the Board of Censors of the Missouri Institute of
Homeopathy.
Member of the American Institute of Homeopathy.
Member of the Southern Homeopathic Association.
Member of the American Association of Orificial Surgeons.
Member of the Southern Homeopathic Medical Society.
Member of the Kansas City Society of Medical Research.
Honorary member of the Chicago Society of Medical Research.
In December, 1911, numerous newspaper clippings show that Dr.
Ottofy was obtaining much publicity relative to his antivaccination
activities. At that time the papers reported that Ottofy was suing the
St. Louis Board of Education for $25,000 damages, because the board
would not admit to the schools of the city a child he had “internally”
vaccinated. In November, 1913, the St. Louis _Republic_ reported that
Ottofy had claimed to have discovered a serum for the cure of cancer,
and quoted Ottofy as claiming “a record of 72 per cent. of cures” in
“selected cases.” In February, 1914, the newspapers reported that
Ottofy was making a trip east “on the trail of radium for use in his
practice in the cure of cancer” and quoted him as stating, “I have
learned on good authority that there is radium in Missouri, and just
where I refuse to divulge at this time.” In January, 1915, the St.
Louis _Republic_ reported that Ottofy, at a meeting of the “St. Louis
Society of Medical Research,” had announced that he had perfected a
serum treatment for cancer, which “is curing patients who have been
pronounced incurable by so-called ‘cancer experts.’” In January, 1916,
the St. Louis _Star_ reported that Ottofy had sought an injunction
against the Board of Education of St. Louis to restrain it from using
its funds for “the maintenance of a Board of Hygiene.” In July, 1916,
St. Louis papers recorded that Ottofy, who was then running for
coroner, had been cited to appear before the prosecuting attorney to
explain a charge of passing out, at a political meeting, a card alleged
to have borne an indecent drawing of President Wilson. The prosecuting
attorney was said to have instructed Ottofy to bring the plates from
which the cards were printed to his office. Two days later the papers
stated that Ottofy had sent the cards and plates by messenger to the
prosecuting attorney’s office.
N. La Doit Johnson, M.D., Chicago.--Dr. Johnson’s name appears as the
“First Vice-President” of the Allied Medical Associations of America.
A few years ago, Dr. Johnson’s name also appeared as the “Dean of the
Faculty” of the “American Post Graduate School.” This “school” was
a mail-order concern which, according to the “Annual Announcement,”
would grant diplomas and confer degrees as follows: “Master of
Surgery,” “Bachelor of Medicine,” “Bachelor of Science,” “Master of
Electro-Therapy,” “Doctor of Osteopathy,” “Doctor of Psychology,”
“Master of Massage,” etc.
H. M. Goehring, D.O., M.D., Pittsburgh, Pa.--The “Second
Vice-President,” according to the letterheads of the “Association”
carries the letters D.O., M.D., after his name. So far as our records
show, and they are most complete and based on official data, H. M.
Goehring is an osteopath, but not a doctor of medicine.
A. E. Erling, M.D., Milwaukee, Wis.--A. E. Erling, according to the
stationery, is “Chairman” of “Censors.” Our records fail to show that
Erling ever graduated in medicine. The Health Department of Milwaukee,
however, says that Erling, when interviewed, claimed to have “a diploma
from the German Medical College of Chicago, but refused to show or
present the same.” The American Medical Directory has this item:
_German Medical College_, Chicago. Chartered Dec. 28, 1891, by
Johann Malok. Fraudulent. Extinct.
A few years ago Erling was in La Crosse, Wis.; and in 1908 a circular
letter bearing his name and picture was sent out from which the
following extracts are taken. Capitalization as in the original:
“Dear Friend:--Permit me to call your attention to the fact that
Dr. A. E. Erling, the eminent specialist, after many years of
travel, practice and medical research, has given up his extensive
road practice and severed his connection with the several medical
institutes which have heretofore occupied considerable of his
attention ... Dr. Erling’s success in the treatment of all CHRONIC
DISEASES is truly remarkable. NERVOUSNESS, all BLOOD DISEASES,
RHEUMATISM, DISEASES PECULIAR TO WOMEN, CATARRH, DEAFNESS, CHRONIC
CONSTIPATION ... APPENDICITIS ... PILES, STOMACH TROUBLES, PARTIAL
PARALYSIS, etc., give way as if by magic under his skillful method
of treatment ... Understand please, that Dr. Erling DOES NOT ACCEPT
A CASE FOR TREATMENT unless he can PROMISE A SPEEDY AND POSITIVELY
PERMANENT CURE.”
The Journal also has in its files advertisements (vintage of 1915),
from some Wisconsin country newspapers, which notify the afflicted that
“Drs. Erling and Karass, the expert German Specialists,” could be seen
in their offices in the “Schlegel Hotel,” the “Schlitz Hotel,” etc., as
the case might be. Whether one of these “German Specialists” was Dr.
Arnold E. Erling, The Journal does not know. Official medical records
fail to show, at least, that there is any other Erling in the state of
Wisconsin.
W. W. Fritz, M.D., Philadelphia.--Another of the “Censors.” This
presumably is W. Wallace Fritz, M.D., D.D.S., N.D., D.O., D.C., who
was the “Dean” of the “American College of Neuropathy,” and “Professor
of Neuropathy” at the same institution. According to newspaper reports
published when the “dean” of the American College of Neuropathy was
called into court to testify regarding the “school,” Fritz admitted
that when he became dean of this “college,” the “college” had three
students and thirty “Faculty Members”! Fritz, it should be mentioned in
passing, is a member of the Philadelphia County Medical Society and by
virtue of this membership he has qualified as a Fellow of the American
Medical Association! Recently Fritz’s name appeared in connection with
the formation of a new organization, founded, it appears, for the
laudable purpose of fighting the “Medical Trust.” Fritz, according to
the newspaper reports, is treasurer of this new organization, which has
adopted the inspiring title, “Constitutional Liberty League of America”
and seems to be a later edition of the mushroom “National League for
Medical Freedom.” Quoting from the newspaper report:
“Dr. W. Wallace Fritz, a member of the American Medical
Association, created a profound impression when he said that all
health laws were written by agents of, or members of, the American
Medical Association, and that this organization was at once the
most powerful and the most baneful of all the American Trusts. Dr.
Fritz then went on to say: ‘Most of the drugs administered are
worthless. Most of the doctors who prescribe them are incompetent,
but both the injurious drug and the ignorant prescriber are
protected, in and out of court, by the American Medical
Association, which trust is now raising a vast fund with which to
drive all drugless healers out of the profession. Medicine is the
camouflage used to conceal the most alert, the most rapacious and
the least patriotic of all the trusts milking the American people.
The tyranny of the Medical Trust is unbelievable. It is also
un-American.’”
The Philadelphia _Sunday Transcript_ of May 4, 1919, had a five column
article under the name of W. Wallace Fritz. It is a most vituperative
affair, and reeks with fire and brimstone. It is directed chiefly
against the American Medical Association, and physicians are dubbed
“Prescription Writing Drug Peddlers Who Prosper Through Monopolistic
Laws Rather than by the Practice of an Exact Science.” In the course of
this diatribe we read:
“The members of the American Medical Association are manifesting an
unwarranted interest in the dear people, who, in their assumption,
need quinin and mercurial guardian; who under this class
legislation confines us to this monopoly of the big and little
pill, is trying by hook and crook to shut out the natural and
rational methods of cure which are driving the drug monopoly from
the face of the earth. Diagnosis and consultation consist in four
or five medical doctors, whose faces denote death, sitting around a
sick man and guessing what ails him. After that has been performed
they guess at what will cure him, and that is generally a sure sign
the undertaker will follow.”
C. O. Linder, M.D., Spokane, Wash.--This gentleman (another “Censor”),
seems to be an osteopath, who some years ago was “Assistant Secretary”
of the “Washington’s Physicians’ Association,” founded apparently
by rebels within the osteopathic ranks who denounced the Washington
Osteopathic Association as a “professional trust”! Linder apparently
claims graduation in 1905 from the “Thompsonian Medical College” of
Allentown, Pa. The following item from the American Medical Directory
regarding this school is of interest:
“_Thompsonian Medical College_, Allentown. Organized in 1904.
Fraudulent. No evidence to show classes were ever held.”
A. H. Flower, M.D., Boston.--Still another “Censor.” Flower, according
to the notice that appears in Polk’s Directory for 1917, claims
graduation in 1888 from the “American Health College” of Cincinnati,
and in 1894 from the “American Health University” of Chicago. Quoting
again from the American Medical Directory, here is what we find
regarding the former “college”:
“_American Health College_, Cincinnati. Organized in 1874 and
re-organized in 1876. Conducted by a Dr. Campbell who originated
and copyrighted the so-called ‘Vitapathic System,’ Fraudulent.
Extinct about 1888.”
We have no record of an “American Health University” of Chicago,
although there was an “Illinois Health University” of Chicago, one
of the numerous diploma-mill swindles operated by Armstrong. It was
declared fraudulent by the federal authorities and its charter was
revoked in 1897. Flower, according to the notice in Polk’s Directory,
is:
Ex-President Maine Eclectic Society.
Ex-President New England Eclectic Medical Association.
Member National Eclectic Medical Association.
Member American Progressive Medical Society.
Member Massachusetts Eclectic Medical Society.
Z. L. Baldwin, M.D., Kalamazoo, Mich.--Possibly the data just given
concerning some of those whose names appeared on the organization’s
stationery are more than sufficient for the average physician to get a
perspective of the Allied Medical Associations of America. Still, it is
worth mentioning that in a letter recently sent out by Ignatz Mayer,
extending an invitation to the annual convention of the Allied Medical
Associations of America, Mayer took the opportunity of incorporating in
his letter a letter which one of the members of the “association” had
been sending out, urging individuals to join. The member in question
was Dr. Z. L. Baldwin of Kalamazoo, Mich. Dr. Baldwin, as some of
our readers may remember, is the gentleman who, a few years ago, was
exploiting an “Intravenous Treatment” for the cure of tuberculosis.
According to the claims made at that time:
“... for the first time in the history of medicine, we have a
successful treatment for tuberculosis.
“... we are able to kill the germs of the disease in the body,
thoroughly ridding it of all tubercular infection, destroying the
germ and its poisons likewise.”
This was a few years ago. Whether Dr. Baldwin is still specializing in
consumption we do not know; apparently not, as we notice that at the
first meeting of the Allied Medical Associations, Baldwin’s name was on
the program for the “Cure of Goiter by Adjustment of Lenses.”
George Starr White, M.D., F.S.Sc., Lond., Los Angeles, Calif.--A
letter received by a physician a few days before the recent convention
of the Allied Medical Associations, held out as an inducement to be
present the fact that “Geo. S. White will show you how to diagnose
disease by means of dif. colored lights and the reaction of the body
to the magnetic meridian.” Dr. George Starr White was the “Second
Vice-President” of the Allied Medical Associations in 1918. White,
according to our records, was graduated in 1908 when he was forty-two
years old, by the New York Homeopathic Medical College and Hospital.
He was licensed in New York in 1908, in California, Connecticut and
Nevada in 1913, and in Michigan in 1916. He seems to have been one
of the proponents of “spondylotherapy,” “zonetherapy,” etc., and
in 1915 it was announced that he would give one week courses in
“Spondylotherapy” in Chicago, Kansas City and Denver, respectively. In
his advertisement he emphasized that he was a Fellow of the American
Medical Association, which, while true at the time, is no longer
true, as on Feb. 4, 1916, he was expelled from membership in the Los
Angeles County Medical Association. In May, 1915, White was arrested
in Chicago and fined $100 and costs for practicing medicine without a
license. Dr. White’s specialty seems to be what is ponderously known
as “Bio-Dynamo-Chromatic Diagnosis.” This has been described by one of
its enthusiastic adherents as “Diagnosis by Sympathetic Vagal-Reflex.”
To obtain the “Sympathetic Vagal-Reflex” it seems the patient must face
east or west and have his bare abdomen percussed until a dull area is
located. The patient is then faced north or south and again percussed.
Then, it seems, different colored lights are thrown on the patient,
the location of the areas of dullness being determined meanwhile. A
combination of ruby and blue lights “will cause a reflex in cases of
gonorrhea,” a “green light will cause a reflex in cases of liver or
gallbladder trouble,” while the color for carcinoma is orange red!
During the height of the influenza epidemic last winter, White seems
to have put on the market “Valens Essential Oil Tablets” which were
for “Gripping the Flu out of Influenza,” and were also said greatly to
benefit or cure incipient tuberculosis, hay-fever, asthma, and “catar.”
The letters “F.S.Sc., Lond.” after Dr. White’s name look well, sound
well, and have an air of erudition and mystery that is well worth what
they cost. They mean “Fellow of the Incorporated Society of Science,
Letters and Arts of London, Ltd.” The “Fellowship” costs one guinea.
Not a few “patent medicine” exploiters in the United States carry
these mystic letters after their names. The society in question was a
seriocomic concern that was exposed by London _Truth_ some years ago
and was also dealt with in The Journal of May 29, 1909, in connection
with the “Aicsol Consumption Cure” exposé.
So much for the Allied Medical Associations of America. At their
recent meeting in New York City they got much newspaper publicity
because of their action on the prohibition question. According to the
newspaper reports, the organization adopted a resolution declaring
that “properly brewed lager beer is absolutely essential in the
treatment of certain cases.” They were further reported as endorsing
the manufacture of light wines and of beer containing not to exceed
2.75 per cent. alcohol. As a piece of publicity work this resolution
was all that its sponsors could expect. The Journal office was
flooded with telegrams and letters from physicians, temperance workers,
congressmen, church organizations, and others, asking, in effect, What
_is_ the Allied Medical Associations of America? This is our apology
for giving the amount of space necessary to a proper understanding of
this organization. Today the rocket of the Allied Medical Associations
of America is blazing a more or less erratic course across the sky of
publicity. The stick will be down anon! Any resolution or expression
of opinion by this organization, or others of its type, when dealing
with the broader problems of public health, is wholly without
scientific significance, whether such resolutions are good, bad or
indifferent.--(_From The Journal A. M. A., July 5, 1919._)
“ARSENICALS”
The September issue of the _Archives of Dermatology and Syphilology_
presents a number of significant features regarding the use of
arsphenamin and related compounds that are at present being widely
employed in the treatment of syphilis. To one who studies these
statements of laboratory and clinical investigators in the special
field involved there must come the conviction that many therapeutic
perplexities still remain at the end of nearly a decade of trial for
the types of compounds which Ehrlich introduced. It is well for the
practitioner to realize this, especially when expert workers still
make an appeal for conservative interpretations. Stokes forcefully
summarized the situation when he stated at the New Orleans session of
the American Medical Association:
Too short a time has elapsed since the discovery of these drugs,
and too little is as yet known about the ultimate problems of the
pathology, immunology and parasitology of syphilis, to justify the
announcing of new infallibilities. The necropsy pathologist of the
next fifty years may well, like Warthin, upset our most plausible
generalizations of today. Seasoned tradition and conservatism are
still the wisest guides in our interpretation of clinical cure.
Arsphenamin has made it apparently possible and even probable,
but only to the inexperienced has cure been made absolute and
inevitable.
It is recognized that the exact composition of arsphenamin in its
available form is not fully determined. As has been emphasized again,
the quantitative determination of arsenic alone in arsphenamin is
insufficient to estimate its purity; in fact, the interstate sale of
arsphenamin is controlled by toxicity tests on guinea-pigs made by
the Hygienic Laboratory of the United States Public Health Service.
Consequently, practical medicine must be on its guard to employ a
product which is carefully controlled by such toxicity tests as well
as by other criteria. It will not do to charge untoward results offhand
solely to idiosyncrasy of the patient, faulty administration or other
errors in technic. The drug itself still has inherent dangers. It
should be borne in mind also that neo-arsphenamin behaves differently
in the animal organism from arsphenamin, and should not be regarded
simply as arsphenamin in a convenient form for administration.
It is gratifying to learn from a government expert that after the long
struggle to produce satisfactory products, arsphenamin preparations
made in the United States are generally less toxic than those of
foreign manufacture. Neo-arsphenamin preparations made in the United
States compare favorably, and in certain instances are decidedly less
toxic than most of the foreign products. Timely presentations of the
faults and dangers as well as the undisputed advantages of current
therapy in the management of syphilis should be welcomed.--(_Editorial
from The Journal A. M. A., Oct. 9, 1920._)
Pharmacology of Arsenicals
The Public Health Service some time ago[262] warned against the use in
syphilis of new arsenicals which are not related to arsphenamin; it was
stated that a number of such were being sold with unwarranted claims
as to their value. At least three such arsenicals have in recent years
been the subject of some exploitation for use in this disease: sodium
cacodylate, the sodium salt of methyl arsenic acid (“Arrhenal”) and
the sodium salt of ethyl arsenic acid (“Mon-Arsone”).[263] As regards
the first two, Castelli showed several years ago that neither has any
action on experimental trypanosomiasis and spirochete infections;
careful clinical observations in this country have confirmed the
inefficacy of sodium cacodylate in human syphilis.[264] Voegtlin
and Smith[265] of the Hygienic Laboratory have now shown in animal
experiments that ethyl arsenic acid (“Mon-Arsone”) is devoid of any
practical trypanocidal action. Thus the “therapeutic ratio” (the
ratio of the minimal effective dose to the lethal dose) was about 1,
that is, it was effective therapeutically only in approximately fatal
doses, the therapeutic ratio for arsphenamin in similar conditions
was 17, and that of neo-arsphenamin, 28. In fact, the conditions
with ethyl arsenic acid were no more favorable than were those with
arsenous acid (the active constituent of solution of potassium
arsenite), although it was far less poisonous. The validity of such
experiments in determining the probable value of drugs in human
syphilis cannot be questioned:[266] it was by such experiments that
Ehrlich and his co-workers found two or three of six hundred and six
arsenic preparations studied to be of value, and of the next three
hundred or more studied only one (neo-arsphenamin) worthy of trial in
human medicine. The time has passed when a high arsenic content of a
compound and a low toxicity, and a number of cases of apparent clinical
improvement, can be assumed to indicate that a drug has any real value
in the treatment of syphilis. Many organic compounds of arsenic as
well as other drugs may cause temporary or apparent improvement in
syphilis, but to date only those related to arsphenamin have proved of
real value and comparatively safe. Others which had some real value
proved to have dangerous side effects; readers will recall the history
of arsanilic acid (“Atoxyl” or “Soamin”) and its acetyl derivative
(“Arsacetin”).--(_Editorial from The Journal A. M. A., Feb. 26, 1921._)
[262] Warning Against Untried Medicaments, J. A. M. A. =74=:1654 (June
12) 1920.
[263] Wright, B. L.; Kennell, L. A., and Hussey, L. M.: Med. Rec.
=97=:607 (April 10) 1920.
[264] Nichols, H. J.: Salvarsan and Sodium Cacodylate, J. A. M. A.
=56=:492 (Feb. 18) 1911.
[265] Voegtlin, Carl, and Smith, H. W.: J. Pharmacol. & Exper. Therap.
=16=:449, 1921.
[266] Compare Schamberg, J. F.; Kolmer, J. A., and Raiziss, G. W.: Am.
J. M. Sc. =150=:25 (July) 1920.
Salvarsan: Abrogate the Patent
The Journal has already commented on the difficulty in securing
salvarsan, on the moral and ethical question as to whether or not it is
justifiable for one person to control the output of a drug necessary to
public health. This week we publish an account of the action of the St.
Louis and Chicago medical societies, which are calling on the medical
profession to appeal to their senators and congressmen to abrogate this
patent. The Journal believes that this patent should be abrogated, not
alone because the patentees have not supplied the demand, not alone
because they have dictated to the medical profession who should have
the drug and how much a physician might have, not alone because of
the war with Germany, not alone because of the special needs of the
government at this time for the control of venereal diseases, not alone
because, as some claim, the patent at Washington does not correctly
describe the product, but also because the people who are supplying
this product are charging prices that are exorbitant compared to the
price at which others in this country can supply it. The fact is that
the salvarsan one can obtain today costs $4.50 per ampule of 0.6 gram,
whereas the same dose of arsenobenzol--a preparation identical with, if
not better than, salvarsan--costs $2.00 at retail, and as Dr. Schamberg
says: “If we are permitted to continue marketing the same drug after
the war, we can sell it at $1.00 or less per tube.” To abrogate this
patent would be doing an injury to no one. Certainly the patentees of
salvarsan have already reaped their harvest--and a pretty rich one. The
supply of salvarsan at a reasonable price in proportion to its actual
cost of production is in the interest of the health of the entire
population of the country, whereas to let matters rest as they are,
is to the benefit of one man. While we are emphasizing here the cost,
there is after all a greater question, and that is the supply necessary
to help control the ravages of one of the most serious diseases
which afflict humanity today. It is the duty of Congress to abrogate
the patent on this preparation and, incidentally, on all medicinal
preparations of importance.--(_Editorial from The Journal A. M. A.,
April 21, 1917._)
End the Monopoly
The Adamson Bill, known as the “trading with the enemy act,” has
recently been passed by the House of Representatives, is now before
the Senate, and will doubtless be enacted into a law. One of its
clauses confers authority on the Federal Trade Commission to grant
licenses to citizens of this country to operate patents owned by enemy
aliens. Physicians are interested in the bill primarily because it
includes the salvarsan situation. The manner in which salvarsan has
been supplied in this country has been so arbitrary and the prices
charged so tremendously above the actual cost, that we should not be
satisfied unless the monopoly is ended so that the drug can be supplied
at least at a fairly moderate figure, and the old methods eliminated.
It is to be hoped, therefore, that the Federal Trade Commission will
not grant exclusive control--that is, exclusive license--to any one
person or firm. To do so would simply perpetuate the old monopoly and
the old conditions. England has adopted a law, which, in principle,
is similar to the Adamson Bill, and there several concerns have been
licensed to manufacture the product. The same should be done here. The
Dermatologic Research Laboratories of Philadelphia announce that they
can supply arsenobenzol at $1.50 a tube, and that there is immediately
available a supply sufficient for any demand that may be made. The same
laboratories have announced also that in a few months they will be able
to supply hospitals for $1.00 a tube. Considerable responsibility rests
on the Federal Trade Commission in this matter, for it is not only a
question of monopoly, but also a question of scientific qualifications
and ability to make the product on the part of some who may make
application. Undoubtedly the commission will secure the cooperation of
the United States Public Health Service, under whose supervision these
drugs should be manufactured no matter who shall be licensed to make
the product.--(_Editorial from The Journal A. M. A., July 21, 1917._)
Arsphenamin
No, this is not a new chemical; it is simply the name adopted
by the Federal Trade Commission for the hydrochlorid of
3-diamino-4-dihydroxy-1-arsenobenzene--in other words, salvarsan. As
our readers already have been informed three firms have been licensed
to manufacture and sell arsphenamin; but, while each manufacturer may
have his own trade name on the label, the official name must be the
prominent one on all packages. Hence, physicians should at once make it
a point to learn and use the name “arsphenamin” in place of salvarsan.
At first sight, arsphenamin looks formidable. In reality, it is just as
easy to familiarize oneself with the word “arsphenamin” as it was to
learn to use the terms “salvarsan,” “arsenobenzol” or any other of the
trade names.--(_Editorial from The Journal A. M. A., Jan. 19, 1918._)
BEER AND CANCER CURES
Did the Brewing Interests Advertise Autolysin?
Our readers may remember that an article appeared in this department of
The Journal for July 6, 1918, under the title “Henry Smith Williams and
‘Proteal Therapy.’” “Proteal Therapy” is a treatment exploited by Henry
Smith Williams, M.D., of New York, for use in tuberculosis, cancer,
rheumatism, etc. It is apparently a modification of the “Autolysin”
cancer “cure” which Williams had previously puffed in _Heart’s
Magazine_.
The Journal’s article pointed out that Henry Smith Williams, although
entitled to write “M.D.” after his name, is essentially a journalist.
He has written voluminously for some years in lay publications on
various subjects, both under his own name and under his _nom de plume_,
“Stoddard Goodhue, M.D.” In addition, Williams runs a publishing
concern called the Goodhue Company, which issues a number of books,
many of them being reprints of Williams’ own articles.
Closely associated with Henry Smith Williams is his brother, Edward
Huntington Williams, who also is a prolific writer. The Journal’s
previous article called attention to the fact that there had been sent
broadcast to physicians a neat little cloth-bound book, entitled,
“Alcohol, Hygiene and Legislation.” This book, which evidently cost
somebody a good deal of money to distribute gratis, was published by
the Goodhue Company, and was written by Edward Huntington Williams.
Enclosed with the book was an advertising leaflet on the “Autolysin”
cancer cure and also a letter from the Goodhue Company, asking
physicians to accept it “with our compliments and the compliments of
the author.” The letter was chiefly devoted to calling attention to
Henry Smith Williams’ “new book, the Autolysin Treatment of Cancer.”
The last thirteen pages of the book “Alcohol, Hygiene and Legislation”
contained advertisements of the Goodhue Company’s publications,
particular emphasis being placed on the “Autolysin Treatment of
Cancer,” by Henry Smith Williams.
So much by way of retrospect. Now comes information that may throw
an interesting side-light on the matter just presented. There is at
present being conducted by a committee of the United States Senate,
an investigation relative to the purchase of a Washington (D. C.)
newspaper with money alleged to have been furnished by those interested
in the brewing industry.
At the opening hearing before the Senate Committee, Tuesday, November
19, the secretary of the United States Brewers’ Association, after
admitting that brewers’ propaganda had been published in the
_International Monthly_, edited by Viereck (of the _Fatherland_), also
declared that the Publication Committee of the brewers’ association
employed writers to “write up certain subjects” relating to the
brewers’ trade. One of the writers mentioned in this connection was,
according to the newspaper reports, “Dr. Edward H. Williams, author of
articles published in medical and other journals.”
With this fact before us, it seemed worth while to go through the
book that had been distributed so lavishly to physicians with the
compliments of the Goodhue Company and Dr. Edward Huntington Williams,
in the exploitation of “Autolysin,” and Henry Smith Williams’ book on
the subject.
The first chapter of “Alcohol, Hygiene and Legislation” consists of
a reprint of an article from the _New York Medical Journal_ of May
8, 1915. The article is a skilful presentation of the case for the
defenders of the lighter alcoholic beverages, especially beer. This
chapter and all succeeding chapters of the book attempt to discredit
prohibitory legislation, and argue that prohibition drives the public
to the use of the more ardent alcoholic beverages, while preventing the
use of the milder beverages, such as beer, which one is led to infer
is not particularly harmful. Throughout the book, also, the state of
Kansas is held up as an example of the harm done by prohibition, and
the theme is developed that insanity and the use of cocain and other
habit-forming drugs follows in the wake of prohibition. The following
extracts are from Chapter I:
The evil effects of _beer_ and wine, for example, are greatly less
than those produced by spirituous liquors.... [Italics ours.--Ed.]
If our theory of immunity is correct we should expect to find that
the older beverages, such as _beer_ and wine, which have been
used for thousands of years, are less productive of alcoholic
insanity, for example, than the spirituous liquors which are recent
innovations. In point of fact we find this to be the case: the
spirituous liquors are almost wholly responsible for all forms of
alcoholic insanity. [Italics ours.--Ed.]
Chapter II is a reprint of an article that appeared in _Everybody’s
Magazine_, August 1914, and deals with “Legislation from a Medical
Viewpoint.” It is to the effect that drug addiction and insanity,
together with special forms of mental disease directly attributable to
alcoholism, seem to flourish best in prohibition territory.
Chapter III deals with “The Peace and War Footing of Alcohol,” and
is a reprint from the _Medical Record_, Aug. 7, 1915. It, too, sings
the praises of the “lighter beverages,” while deprecating the use of
“ardent spirits.” For instance:
An overwhelmingly large proportion of persons who develop alcoholic
psychoses in America are drinkers of whisky, or some corresponding
ardent spirit, whereas this condition is seldom seen in _beer_ and
wine drinkers. [Italics ours.--Ed.]
Thus we find the highest percentage of alcohol psychoses among
the whisky drinkers who come from western Europe, while the wine
and _beer_ drinking races of central and southern Europe show
a distinctly lower percentage, in some instances only about
one-fourth as many per thousand. [Italics ours.--Ed.]
Chapter IV deals with “Some Aspects of Liquor Legislation.” Like
Chapter II it is an indictment of prohibition, and the United States
Census Bureau’s reports are called on to sustain this thesis.
Quotations, too, are made from the writings of Henry Smith Williams
further to prove the point. “Dry” Kansas and “wet” Nebraska are
frequently compared, to the detriment of the former. One who accepts
the statements in this chapter will get the impression that Kansas has
more lawlessness, illiteracy, pauperism, and insanity than Nebraska.
Chapter V deals with “The Problem of Legislation.” It is based on the
premise that “prohibition does not prevent the consumption of liquor,”
but on the contrary, “prohibitive legislation induces the consumption
of the most harmful form of liquors.” Stated in another way, it is
equivalent to charging that prohibition is hard on the brewers, but
beneficial to the distillers. In fact, E. H. Williams, in another book
(“The Question of Alcohol”--Goodhue Co.) which also champions the case
for the milder alcoholics, quotes Henry Smith Williams as saying,
relative to prohibitory legislation: “In general, it would appear
that, if our legislators of recent years had been in league with the
distiller, they could not have served his purpose better.”
Whether or not Edward H. Williams’ or Henry Smith Williams’ conception
of the alcohol problem is good, bad or indifferent, need not at this
time concern us. The medical profession, however, has a right to ask
two questions: First, Is the Dr. Edward Huntington Williams who wrote
“Alcohol, Hygiene and Legislation” the “Dr. Edward H. Williams” who was
employed by the brewers to write propaganda favorable to the brewing
interests? Second, Was the cloth-bound book, “Alcohol, Hygiene and
Legislation,” which was distributed by the Williams brothers, paid for,
wholly or in part, by the United States Brewers’ Association?
For those who wish to read Dr. Edward Huntington Williams’ opinion on
the alcohol question, the following bibliography may be of service:
“Liquor Legislation and Insanity”: _Medical Record_ =84=:791, 1913.
“The Liquor Question in Medicine”: _Medical Record_ =85=:612, 1914.
“Inebriety as a Medical Problem”: _Post-Graduate_ =29=:603, 1914.
“The Problem of Inebriety”: _N. Y. Medical Journal_ =101=:940, 1915.
“Aspects of Inebriety in Alcohol”: _British Journal of Inebriety_
=13=:9, 1915-1916.
“The Peace and War Footing of Alcohol”: _Medical Record_ =88=:226,
1915.
“Alcohol and Therapeutics”: _Medical Record_ =92=:666, 1917.--(_From
The Journal A. M. A., Nov. 30, 1918._)
BIOLOGIC THERAPEUTICS AND ITS COMMERCIAL DOMINATION
The danger of commercialized therapeutics has been enormously increased
by the introduction of biologic products. These substances offer a rich
field for the commercially minded, first, because of the remarkable
results which seem to have followed the use of certain products of
this type; second, because the field is new and the mode of action
of these substances not readily understood and, third--and most
important--because, by the very nature of the problems involved, few
physicians are well informed concerning them. The influenza epidemic of
last year was widespread and fatal in character. It stimulated earnest
research in methods of prevention and cure. We were all in a frame
of mind to grasp at any straw. Here and there some worker would cry
“Eureka”--only to be disappointed when his product was actually put to
the test. However, there were more than enough manufacturers ready to
place any product on the market with specious claims that could not
be positively denied. Vaccines, serums, proteins--all were advanced
with such glowing statements as to their properties that only those
physicians who kept their feet firmly on solid ground could resist
the appeal. Now we have had another epidemic--mild, it is true--but
the memories of last year make the average physician ready to accept
anything which promises hope, and the manufacturers “make hay while the
sun shines.” Physicians have been and are being deluged with literature
on the prophylaxis and treatment of influenza. So far as we know, few
publications have contained any word of warning on these matters. One
exception has just come to notice: the _Medico-Military Review_, a
semimonthly mimeographed publication sent to medical officers of the
Army by the Surgeon General’s Office. This says:
YOU ARE REMINDED that so far a comprehensive analysis of results
obtained by the use of monovalent and polyvalent vaccines in the
prevention of influenza has not demonstrated their value. Much
carefully controlled experimental work is now being carried out
on this subject both in civil institutions and in the Army, and
any worthwhile advances will be reported in the _Review_ from
time to time. If a prospective vaccine is developed, it will be
prepared at the Army Medical School for general distribution and
all medical officers will be duly notified. The general use of the
present commercial polyvalent protective against influenza is not
considered desirable. Numerous telegrams and other requisitions are
being received for influenza vaccine. In view of the fact that no
prophylactic influenza vaccine is available, such requisitions should
be discontinued.--(_Editorial from The Journal A. M. A., Feb. 14,
1920._)
CAPELL’S UROLUETIC TEST
U. S. Marine Hospital, Chicago.
_To the Editor_:--A member of the consultant staff of this hospital
recently referred to us a “Doctor” H. F. Matthews, who was supposed
to give demonstrations of a new test for syphilis--“Capell’s
‘Uroluetic’ Test.” The test was to be made of the urine of the
patient. The above mentioned consultant was under the impression
that the said “Doctor” Matthews was a graduate physician.
“Doctor” Matthews came to the hospital according to the appointment
made by the consultant, and proceeded to give his demonstration.
Several of the junior officers and interns were present to
witness it. He was asked questions in an attempt to determine
the scientific status of the test which he was demonstrating.
His answers were always vague and indefinite and not clothed in
scientific words.
We became suspicious of him, and he was asked if he was a graduate
physician. He admitted that he was not. He was further asked if he
had studied chemistry and bacteriology; he stated that he had in
1888. Inquiry was made as to where; he replied that it was at the
University of Illinois. He was further asked if he was familiar
with the Wassermann reaction. He stated that he was not.
This man is going around representing himself as a physician who
has a new test which he claims is superior to, and more delicate
than, the Wassermann test; yet he knows nothing whatever of the
technic of the Wassermann reaction.
In one case, we gave him the same specimen of urine in four
different containers. He read a different degree of reaction for
each of them. In other words, in a specimen from the same patient,
his four different tests showed, respectively, a +, a ++, a +++ and
a ++++ reaction.
It occurred to me that it might be well to inform you of this
man’s methods, as he told us that he had been to a good many
institutions, and I am sure he will soon start a plan to
systematically force his pseudoscientific test on credulous
physicians everywhere.
J. O. Cobb, M.D., Senior Surgeon in Charge.
The Propaganda Department has in its files a business card reading:
“Capell’s Laboratories, Room 1510 Masonic Temple, Chicago. Dr. H. F.
Matthews, Special Representative.” Capell’s Laboratory has its
headquarters in Omaha, and is apparently conducted by Dr. W. L. Capell,
who, for many years, seems to have been more or less interested in
proprietary medicines. Some years ago he was connected with a concern
known as “Acneine Pharmacal Company,” which, apparently, was dissolved
some time in 1910; and soon thereafter a new company was organized
known as the LeRoy Drug Company. In 1917 W. L. Capell was connected
with the Capell, Cameron Co., Inc., of Lincoln, Neb., which was
selling “Capell’s Uroluetic Test”, “Capell’s Treatment for Syphilis”
and other remedies. The “Treatment for Syphilis” was said to be
“Painless, Pleasant, Harmless, Efficacious, and requires usually
from 30 to 90 days only to eradicate the disease.”
The name of the treatment is “Mercarodin”--earlier it was called
“Camit”--and it is now being sold from “Capell’s Laboratory,” Omaha.
In addition, Capell’s Laboratory sells Acneine, which apparently is
the same product that was sold in 1906 and 1907 under the name of
“Sambu-Co” by the Holtman-Stringer Co. of Omaha and later was put out
by the Acneine Pharmacal Company of Omaha.
While Capell’s Laboratory sells proprietary remedies, it is the
“Uroluetic Test” which the concern now seems to be featuring. The
claims made for this are:
“This test requires no expert knowledge, is inexpensive, and can be
made in a few minutes, and is so plain that it cannot be mistaken.”
The idea of being able to determine the absence or presence of syphilis
by a simple color test of the urine is a fascinating one. The present
reliable diagnostic tests are, as Capell’s Laboratory so plausibly
emphasizes, somewhat involved, and call for rather delicate technic.
But there are no short-cuts to knowledge.
A physician who ordered Capell’s Uroluetic Test some weeks ago received
with the bill the letter that follows: It is given not so much for what
it says, as for how it says it. It is copied _verbatim et literatim_:
“Your letter received, and we have mailed you as per your letter
1 Doz. of Capell’s ‘Uroluetic’ Tests. In close find statement and
instructions, for same.
“The ‘Uroluetic’ Test is meeting a far greater approval from the
Medical profession than we had expected, while we do not claime
that it is perfect, yet we have only received one unfavorable
report, and we daily feel incuraged in its efficacy.
“You know Doctor that there are two dangerous elements in this
world, one is the extreme pessimist and the other is the extreme
optimist. The immoral Lincoln said, ‘That there was nothing that
was wholly good or wholly evil,’ and we presume that this is
equally true of the ‘Uroluetic’ test. But we want the truth no
matter what it is.”
“Capell’s Uroluetic Test” would be “important if true.” Unfortunately,
its scientific value to the sufferer is negligible compared with its
economic value to the exploiter. It is not so much a test for lues
in the patient as of credulity in the doctor.--(_From The Journal
A. M. A., Aug. 23, 1919._)
Another Urinary Test for Syphilis
_To the Editor_:--Will you kindly inform me whether the test in the
enclosed “literature” is what it is represented to be?
Charles M. Thomas, M.D., Sunbury, Pa.
ANSWER.--The “literature” referred to by Dr. Thomas dealt with the
“Uri-Na Test” sold by the Standard Appliance Company of Philadelphia.
There seems to be a strong family resemblance between this alleged test
and that known as “Capell’s Uroluetic Test,” which was discussed in
the Propaganda Department of The Journal, Aug. 23, 1919. Of that The
Journal said: “Unfortunately, its scientific value to the sufferer is
negligible compared with its economic value to the exploiter. It is not
so much a test for lues in the patient as of credulity in the doctor.”
The same may be said of the “Uri-Na Test.” The facts are, there is no
method at present known by which the absence or presence of syphilis
may be determined by a simple color test of the urine.--(_Query in The
Journal A. M. A., Nov. 22, 1919._)
CHEMOTHERAPY AND TUMORS[N]
Richard Weil, M.D., New York
[N] From the Cancer Research Service of the General Memorial Hospital,
New York.
[N] This critical discussion of the status of chemotherapy in tumors
was prepared at the request of the Council on Pharmacy and Chemistry of
the American Medical Association.
Within the last three years a number of reports have appeared in the
medical press which bear on the treatment of malignant growths in
human beings by chemical preparations. The most persuasive and the
most insistent claims have been made in connection with the colloidal
solutions of certain metalloids and metals, notably selenium, vanadium
and copper. At the same time a number of drug houses, both in this
country and abroad, have placed on the market proprietary preparations
of these substances in various forms, for which the claim is made that
they produce striking therapeutic effects and sometimes even cures in
malignant neoplasms.
The impulse toward the use and production of this type of preparation
is directly traceable to a series of scientific experiments on the
tumors of animals, which date back no farther than the year 1911. In
that year Wassermann and his co-workers[267] published a report on
the treatment of rat tumors by means of the intravenous injection of
selenium compounds. This paper received wide notoriety through its
enthusiastic diffusion by the lay press. Shortly afterward Neuberg and
his co-workers[268] published their observations upon the therapeutic
effects of certain metallic compounds. The clinical application of the
encouraging results obtained by these authors in animal tumors followed
rapidly, and up to the present time a number of papers have appeared
in which the claim is made that human tumors also may be favorably
influenced through the constitutional use of substances similar to
those used by Wassermann or Neuberg. In some cases, use has been made
of colloidal solutions of the heavy metals, such as copper; in others,
selenium compounds have been used, while in a third set of observations
the therapeutic agent represents an attempt to combine the virtues of
these two types of therapy by employing selenium in colloidal form. As
an example of the first class, may be cited the cuprase of Gaube du
Gers;[269] of the second, the seleniovanadic ointment of Roemer and the
sulpho-selene of Walker; of the third, seleniol and electro-selenium.
[267] Wassermann, Keysser and Wassermann: Deutsch. med. Wchnschr.
=37=:2389, 1911. Wassermann and Hansemann: Berl. klin. Wchnschr. =49=:4,
1912.
[268] Neuberg and Caspari: Deutsch. med. Wchnschr. =38=:375, 1912.
Neuberg, Caspari and Löhe: Berl. klin. Wchnschr. =49=:1405, 1912.
[269] Gers, Gaube du: La cuprase et le cancer, Paris, 1913.
Inasmuch as this new type of cancer therapy derives its origin,
its justification and its support, in very large measure, from the
laboratory results obtained in animals, it is a matter of considerable
importance to examine those results with care, in order to determine
whether they furnish a satisfactory basis for human therapy, and
whether they justify the hopes to which they have given rise.
It is safe to assert that the application of chemotherapy to the
treatment of tumors practically dates from the publications of
Wassermann. He stated the principle that a rational therapy of tumors
must be based on constitutional treatment. It appears evident that
local treatment can have only local effects. The lymphatic extensions
of tumorous growths, and the often unsuspected metastases in distant
organs must of necessity escape the effects of purely local treatment.
Hence, Wassermann reached the conclusion that all treatment of cancer
which was to be effective, and not merely palliative, must be carried
to all parts of the body by means of the blood stream. He therefore
introduced the use of intravenous injections in the experimental
therapy of rat and mouse tumors. An accidental observation led him
to believe that selenium was a substance possessing a high degree of
affinity for tumor cells.
In order to insure the penetration of the tumor in the live animal by
this substance, however, he considered it essential to combine it with
some other highly diffusible substance. This type of substance, which
was to act as a carrier of the selenium, he described under the name
“cytotrochin,” from the Greek word τροχιά {trochia}, meaning road. For
this purpose he selected eosin. The eosin and the selenium were then
combined by a method and in a form the details of which have never
been published. All that we know of this preparation is contained in
the statement that it is very difficult to produce, and that it is
extremely unstable and difficult to keep. Mice can be given amounts of
from 2 to 3 mg. of this substance in solution. Wassermann experimented
with mice inoculated with transplanted tumors of the types of carcinoma
and sarcoma. After from three to five intravenous injections of the
drug, he noted that the tumors become softer and fluctuate. After still
further injections the fluid mass undergoes absorption, and the tumor
gives the impression of an empty sac. If it is possible to carry the
injections up to the number of ten or twelve, recovery ensues. In such
cured animals there remain only the unabsorbed portions of the fibrous
capsule. Recurrences were not observed in the cured animals. Wassermann
further stated that two spontaneous tumors in mice which had been
treated by this method presented favorable results.
Wassermann’s original presentation gave few experimental details, and
has not been followed by the promised scientific report. From his
article it is impossible to determine what proportion of his animals
were cured and what proportion failed to survive the treatment. From a
later paper by Keysser[270] we learn that by far the larger portion of
the animals perished during the treatment in the stage of softening,
so that a cure was accomplished in from only 3 to 5 per cent. of the
animals. This is a point of great importance, inasmuch as it furnishes
an indication of the highly dangerous character of this mode of
treatment. Fatal results are attributed by Keysser to the absorption of
toxic products from the tumor. This contention, however, is supported
by no observations, and it is certainly equally fair to assume that
death results from the toxic effects of the compound. A microscopic
study of tumors taken from animals undergoing treatment was made by
Hansemann. He found that the death of the cells was the result of
nuclear destruction.
[270] Keysser: Wien. klin. Wchnschr. =26=:1664, 1913.
Within a very few months after Wassermann’s publication, Neuberg
and Caspari[268] published a paper which was the first of a series
of studies on the therapeutic effects of the heavy metals on the
animal tumors. They used zinc, platinum, tin, selenium, copper,
silver and cobalt in the form of certain complex organic compounds,
the composition of which is not revealed. Owing to the fact that
intravenous injections of these compounds produced a specific effect on
the tumors, they are described as “tumoraffin” substances. Immediately
after the intravenous injection of these preparations, there followed
a marked hyperemia of the tumor, whereas the remainder of the mouse’s
body appeared markedly anemic. The hyperemia was often attended
by hemorrhage into the tumor. This first stage was succeeded by
liquefaction and absorption followed by recovery in favorable cases.
The authors failed to state in what proportion of their experiments the
animals died, and in what proportion recovery ensued.
The second paper on this subject is by Neuberg, Caspari and Löhe,[268]
in which further details are vouchsafed. They state that with the
compounds used by them the toxic and the therapeutic doses approximate
very closely, from which it follows that the treatment, as with the
Wassermann method, results in a very high mortality. Smaller doses
produce no therapeutic effect; on the contrary, they seem to act as
a stimulus to the tumor, accelerating the normal rate of growth.
Spontaneous tumors show similar effects, but no cures are recorded.
Only in tumors in which autolysis is active _intra vitam_ does the
method exert any effect. Consequently the benign primary tumors of
animals, such as fibromas, are not influenced by it.
Neuberg and Caspari are to a great extent responsible for the colloidal
theory of treatment in tumors. Accepting the observations of Petri and
others that the autolytic ferments in tumors are quantitatively greater
and qualitatively different from those present in the normal tissues
of the body, they venture the assumption that the process of recovery
in the experimental tumors of animals is due to the self-digestion of
the tumor by these ferments. Ascoli and Izar[271] had shown that such
ferments are materially stimulated by the presence of metals, and more
especially of metals in colloidal form. This contention is apparently
in harmony with the well-established fact that certain colloidal metals
of themselves are capable of acting under certain circumstances as
ferments. Neuberg and Caspari were at first of the belief that the
compounds produced by them circulate in colloidal form. Subsequently
they stated that these compounds were crystalline substances, but they
assumed, under the influence of the theoretical consideration mentioned
above, that these substances are broken up in the tumor and there
undergo transformation into the colloid state.
[271] Izar: Ztschr. f. Immunitätsforsch., 1913. Izar and Basile: Berl.
klin. Wchnschr., 1913, p. 1312.
In connection with the preceding observations there are certain other
experimental results which require mention. Izar[271] succeeded in
curing rat tumors by means of injection of colloidal sulphur. C.
Lewin[272] cured subcutaneous mouse tumors with various preparations
of gold. Werner and Szécsi[273] produced similar results through
a combination of selenium-vanadium with cholin-borate; in these
experiments the selenium-vanadium was supposed to be present in
colloidal form.
[272] Lewin, Carl: Berl. klin. Wchnschr., 1913, p. 147; Berl. klin.
Wchnschr., 1913, p. 541.
[273] Werner and Szécsi: Ztschr. f. Chemotherap., 1913, Orig., i, 358.
Szécsi: Ibid., ref., 1913, ii, 1060.
Within a comparatively brief period of time, therefore, it fell to the
lot of a number of observers, using strikingly different substances,
to produce therapeutic effects amounting in a certain percentage of
cases even to cure in the experimental tumors of the lower animals.
The various procedures have little in common. Both metals and
nonmetallic substances have been employed either in colloidal form or
in combination with organic radicals. In some instances a diffusible
carrier is combined with the basic substances; in others not. All of
the preparations appear to possess a high degree of toxicity, although
adequate data on this very essential feature are almost invariably
withheld.
Wassermann’s results with eosin-selenium were soon critically examined
by other observers. Uhlenhuth[274] and Contamin[275] were unable to
confirm his observations, but their negative results are attributed
by Keysser to the fact that they were not in possession of the proper
formula for the preparation of the eosin-selenium compounds as used
by Wassermann. Apolant,[276] however, in Ehrlich’s name confirmed
Wassermann’s findings.
[274] Uhlenhuth, Dold and Bindseil: Ref., München. med. Wchnschr.,
1912, p. 1782.
[275] Contamin, Detoeuf and Thomos: Bull. de l’assn. franç. pour
l’étude du cancer, vi, 62.
[276] Apolant, H.: VI Tag. der freien Vereinigung für Mikrobiologie.,
Berlin, 1912. Ref. München. med. Wchnschr., 1912, p. 659.
The most important critique of eosin-selenium has been contributed
by the subsequent investigations of one of Wassermann’s original
collaborators, F. Keysser.[277] Keysser’s publication contains a large
number of very careful observations on the various forms of eosin
supplied by the German manufacturers, as well as on other matters which
cannot here be considered in detail. He finally reached the conclusion
that the eosin furnished by the manufacturing house of Sandoz was
the most effective for his purposes, inasmuch as it combined the
lowest grade of toxicity with the highest capacity for discoloring
the tissues. The selenium he used in the form of selenio-vanadium
furnished by Clin of Paris, which was the identical preparation used
by Werner and Szécsi in combination with borcholin. The maximum dose
of this selenio-vanadium is 0.06 c.c. for each gram of mouse. Eosin,
0.01 gm., dissolved in 0.5 c.c. of physiologic salt solution, is mixed
with 0.5 c.c. of the selenio-vanadium. This mixture is then used for
intravenous injections. The results produced by the injection of this
mixture are to all intents and purposes similar to those obtained by
Wassermann, except that Keysser induced cure in a larger proportion of
animals, namely, from 6 to 8 per cent. It is evident from his careful
description of his experiments that the treatment is extremely toxic to
the animals. The therapeutic dose is considerably greater than one-half
the toxic dose. This accounts for the fact that an extremely large
proportion of the animals perish during the course of the treatment.
The tumors failed to be influenced unless the dose given fell very
little short of the fatal amount. Moreover, in order to accomplish a
complete cure, at least eight to ten injections must be given, and in
some instances not less than fourteen.
[277] Keysser, F.: Ztschr. f. Chemotherap., 1914, Orig., ii, 188.
Keysser’s most important conclusions, however, were obtained by
following an altogether different line of procedure. It has been
pointed out by Carl Lewin[272] that the therapeutic results obtained
from subcutaneous mouse tumors, however encouraging, could not be
logically applied to the treatment of human cancers. The subcutaneous
transplanted tumors, as is well known, are as a rule limited by a
distinct capsule and show no tendency to infiltrative growth. In this
particular they present a most striking difference when compared
with human tumors. On the other hand, the metastases of mouse tumors
in the internal organs present an infiltrative mode of growth and
thus approximate very much more closely to the human type of tumors.
Keysser, therefore, determined to test the therapeutic effectiveness
of his compounds on tumors implanted in various organs. He developed a
technic which enabled him to implant tumors in the liver, the spleen,
the kidneys and other parts of the mouse by means of injection through
special needles, often without the assistance of a cutting operation.
The tumors so implanted grew rapidly, and within from two to
three weeks reached the size of cherry pits. The growth was
characteristically infiltrative. Animals with these tumors were then
submitted to intravenous injection of the therapeutic agents in exactly
the same fashion as the animals carrying subcutaneous tumors. The
results, however, were absolutely different. Whereas the subcutaneous
tumors invariably showed a much more intense discoloration than the
other tissues of the mouse, this feature was entirely lacking in the
case of the internal tumors. Softening and liquefaction, which almost
invariably follows on the third or fourth injection in the case of
subcutaneous tumors, and which is the first symptom of cure, never
presented itself in the case of the internal tumors. Their consistency
throughout the treatment was indistinguishable from that of the tumors
of control animals. The treatment, in fact, appeared to exercise not
the slightest influence on internal tumors. There was neither cessation
nor retardation in growth, but the tumors continued their normal rate
of destructive increase with the production of metastases, leading
eventually to the death of the animal either during the course of the
treatment or shortly thereafter. Microscopic changes, such as had been
observed by Hansemann in the case of subcutaneous tumors, were entirely
lacking. No matter in what organ the tumors were implanted, these
results remained the same. No matter what type of tumor was employed,
whether carcinoma, adenocarcinoma or sarcoma, the therapeutic outcome
was regularly and consistently nil.
These results induced Keysser to determine whether or not
eosin-selenium could actually be shown to exercise a deleterious
effect on cancer cells outside the body. In order to do this he made a
suspension of mouse tumor cells in salt solution and mixed this with
the eosin-selenium-vanadium, using the latter in amounts equivalent to
three times the fatal dose for a mouse. After the mixture had stood
from one to three hours, it was injected either subcutaneously or
intravenously into mice in order to test the vitality of the cells.
In every instance the injections resulted in the production of tumors
which could be in no way distinguished from the tumors produced by
untreated cancer cells. In other words, the therapeutic preparation had
absolutely no effect on the tumor cells.
In the same way Keysser carried out experiments along the lines
inaugurated by Neuberg, using a combination of glycocoll and copper.
He also tested the combination of borcholin with selenium-vanadium
used by Werner and Szécsi. He was able to confirm the fact that both
of these substances produced an unmistakable therapeutic effect on
subcutaneous tumors. On the other hand, they were absolutely without
influence on the internal tumors. In this respect, therefore, they were
entirely comparable with the eosin-selenium compound. The theoretical
basis constructed by Neuberg, which rests on the assumption that the
metallic compounds stimulate autolytic processes in the tumors, was
also subjected by Keysser to destructive criticism.
Finally, Keysser showed that none of these therapeutic agents were
effective even in the case of subcutaneous tumors, unless the latter
had reached at least the size of cherry pits. If a therapeutic
injection were made immediately after inoculation of the tumors, no
effect was observed. The tumors grew exactly as in the control animals,
and the injected animals died in about the same period of time as they.
All of these facts, which taken together constitute a very remarkable
and convincing piece of scientific investigation, permit of but
one conclusion. It is quite clearly established that none of the
preparations of which the therapeutic effectiveness has hitherto been
proclaimed exercise any direct influence on the life or development
of the tumor. Under certain very definite and restricted conditions,
however, they do appear to produce certain changes in the tumors,
and in a small proportion even cures. These results, however, are
obtained only in the case of tumors which are subcutaneous in location
and not smaller than a cherry pit in size. Keysser’s interpretation
of the striking differences between tumors is of interest in this
connection. He believes that the constant palpation and examination
of the subcutaneous tumors, which is prompted by interest in the
experiment, produces circulatory changes with hyperemia and hemorrhage.
These circulatory changes are responsible for the increased tendency
of the injected substances to lodge in the tumors, thereby possibly
increasing the tendency to autolysis which the circulatory changes have
inaugurated. It is, of course, questionable whether this explanation
can be regarded as final. In a series of experiments which I performed
many years ago, I was able to show that sodium iodid when injected
intravenously accumulates in tumors in larger amounts than in any other
tissue of the body in rats. A similar observation has been recorded
by Wells, De Witt and Corper.[278] In the same way I found that
various dyes, such as Congo red, when injected intravenously, could be
demonstrated in tumors long after the rest of the body had recovered
its normal color; the liver alone vied with the tumors in this respect.
The dyestuff was invariably sharply localized in the necrotic portions
of the tumor. The conclusion seemed obvious that, owing to circulatory
conditions or possibly even to chemical conditions, the dye was
retained longest in the necrotic parts of the tumor. This effect was
unquestionably not due to handling, inasmuch as the animals in my
experiments were not palpated from the time of injection until death.
[278] Wells, H. G., De Witt, and Corper: Ztschr. f. Chemotherap., 1914,
Orig., ii, 110.
I have, however, had an even more striking demonstration of the same
fact. I have given intravenous injections of dyes to patients suffering
with various forms of internal tumors, as, for example, cancer of the
breast, in the hope of favorably influencing the growths. At operation,
the picture presented by the tumor is striking in the extreme. It
presents areas of various size which are intensely discolored by the
dye. These areas, both to the naked eye and under the microscope,
are the necrotic parts of the tumor. The actively growing areas of
tumor tissue and all the normal tissues of the organ present their
normal color. All of these observations lead to the conclusion that
the necrotic areas in tumors either possess a higher affinity for
sodium iodid and for the dyes than do the normal tissues, or that
these substances are more slowly absorbed from the necrotic areas
owing to the circulatory deficiency. Whichever of these explanations
is accepted, it is quite reasonable to believe that necrotic areas
might well undergo liquefaction under the influence of the various
substances which have been used for therapeutic injection. Such a
result is, of course, without direct effect on the growth or vitality
of the living part of the tumor. This fact is quite clearly evidenced
by the experimental data, which show that the internal portions of the
tumor might undergo liquefaction and yet the tumors were not cured.
Indeed, Löhe, who made microscopic examinations of the tumors treated
by Caspari and Neuberg, states particularly, with reference to a tumor
which had been subjected to treatment, that “the central portion of
the tumor showed softening, while the external margin was composed of
actively growing cells.” The central portions of implanted tumors are,
of course, those which first undergo spontaneous necrosis.
It still remains to explain the small percentage of cures achieved by
Wassermann and by Keysser. It does not appear to me that this problem
presents any insuperable difficulties. The fact must be emphasized
that practically 95 per cent. of the animals die under the treatment,
which sufficiently indicates the toxic effects of the agent used. We
must remember that transplanted tumors are under all circumstances
at a certain disadvantage as compared with the normal tissues of the
body. After all, they are implanted on a foreign soil. Their blood
supply is impoverished and imperfect. They have a natural tendency to
undergo necrosis, and in many cases spontaneous retrogression. It is
not strange, therefore, that they should prove in slight degree more
susceptible to toxic effects than are the normal tissues of the body.
If we remember that the various therapeutic agents introduced in all
probability reach a somewhat higher degree of concentration in the
necrotic areas of the tumor than in the normal tissues of the body, an
assumption which is entirely in accord with the facts as observed in
the case of sodium iodid and of various dyes, we may be quite prepared
to believe that this factor is sufficient to induce the destruction of
the marginal healthy and living cells of the tumor. The fact that small
subcutaneous tumors were found by Keysser to be entirely refractory
to the treatment is entirely in accord with this assumption, in view
of the fact that tumors of this size present practically no central
necrosis. The same explanation holds of the observation previously
cited from Caspari that the primary spontaneous tumors of animals
do not yield to the treatment. Indeed, he himself states that the
treatment is effective only in tumors in which autolysis takes place
during life. The word autolysis, however, in this connection is a
misnomer and represents a gratuitous assumption; as an actual fact,
one is entitled to say only that such tumors undergo central necrosis,
in all probably owing to defective circulatory supply. The process is
exactly similar to the coagulation necrosis described in the case of
tubercles by Weigert. If autolysis occurs, it is only secondary to the
preceding necrosis.
This explanation, however, is confronted by the fact that the internal
tumors produced by Keysser showed no tendency to effect a localization
of the dyes, and correspondingly no tendency to be affected by the
therapeutic agents. One might be permitted to inquire whether these
internal tumors had undergone any necrosis. Keysser unfortunately makes
no mention of this matter. It is certainly true that the infiltrative
mode of growth of the internal tumors, which is entirely different
from that of the subcutaneous implantations, is associated with a
much better blood supply and a lessened tendency to undergo necrosis.
That such tumors can undergo necrosis, however, is evidenced by
certain illustrations given by Carl Lewin in his paper on internal
tumors. But such changes usually occur only in advanced stages. To
judge from his plates, Keysser worked with relatively small tumors,
an assumption which is rendered even more likely by the fact that his
injections were undertaken in a fairly early stage of their growth. In
this connection I may quote certain experiments of my own on internal
tumors.[279] The implantations made in my experiments were produced by
intravenous injections of a tumor suspension into the jugular vein of
rats. Such injections resulted almost invariably in the production of
a large number of tumors in the lungs, which, as is well shown in the
figures accompanying the original article, differed very markedly in
size. The smaller of these tumors are composed throughout of actively
growing cells, while the large tumors present an area of central
necrosis exactly as do the subcutaneous tumors. If such an animal be
given an intravenous injection of a dye such as Congo red, it will be
found that the larger tumors present an area of central discoloration
corresponding to the area of previous necrosis, while the smaller
tumors, like normal tissues, are not colored. Thus, it is clear that
the internal tumors implanted in animals are subject to the same laws
concerning the distribution of dyes and, of course, other substances as
are the subcutaneous tumors. As I have stated previously, an exactly
analogous observation has been made in a human breast tumor. In the
absence of any contradictory evidence, therefore, I think that it is
perfectly justifiable to assume that Keysser failed to achieve a result
in the internal growths simply owing to the fact that those growths
presented practically no areas of necrosis at the time of his injection.
[279] J. M. Research, 1913, p. 497.
Another theoretical question which bears closely on the recent
therapeutic investigations in human beings concerns the rôle of
colloids, as such, in the procedure. It is quite clear from what has
already been said that all experiments with animal tumors have been
largely influenced by the belief that metals in the colloidal form
exercise a peculiar and characteristic influence on the destruction
of tumors. Even when the therapeutic agents have been introduced
in crystalline form, as by Neuberg and Caspari, the authors find
themselves compelled to assume that the metals are reduced to colloidal
form within the tumors. For the latter assumption there is absolutely
no evidence; it is due simply to the influence of the colloidal theory.
If one critically examines the data on which this theory is based, one
is forced to the conclusion that it has practically no established
claim to validity. If we grant that colloidal metals have been shown to
stimulate autolysis in the test tube, the same fact must be admitted of
metals in noncolloidal solution. The experiments, however, are very far
from establishing either of these facts satisfactorily. But even were
this the case, it is an unjustifiable inference that living tumor cells
would be influenced in anything like the same manner as are the dead
cells observed in test tube experiments. As an actual fact, we know
from the work of Evans and Schulemann that only the “scavenger cells”
of the body take up foreign colloids, and to this class the tumor cells
do not belong. Moreover, the form in which metals are introduced
into the circulation is not necessarily or even probably the form in
which they act on the tissues. Colloidal solutions of the metals are
certainly subject to precipitation and other changes on entering the
blood. This fact I have shown experimentally in a previous study on
colloidal copper.[280] In the same way it is probable, as has been
pointed out by Wells, that metals when introduced in crystalloid form
may rapidly be altered so that they are carried throughout the body in
colloidal form. All of these considerations indicate how unjustifiable
is the assumption that colloidal metals exercise a peculiar action on
growing tumors. It is hardly surprising that their empiric use has
failed to measure up to expectations based on so slim a foundation of
fact.
[280] Weil, Richard: The Effects of Colloidal Copper with an Analysis
of the Therapeutic Criteria in Human Cancer, J. A. M. A. =61=:1034
(Sept. 27) 1913.
CLINICAL OBSERVATION
Clinicians have not been slow in following the lead suggested by the
therapeutic experiments in animals. It is perfectly proper that this
should be the case. In dealing with a disease of the character of
cancer, in many instances entirely beyond our power to influence, no
one can question the advisability of trying any and every agent which
holds out the slightest promise. Unfortunately, a closer analysis of
the animal experiments fails to vindicate even that degree of faith.
When one considers the facts which have been analyzed in the preceding
discussion, it would appear not only futile but actually dangerous to
attempt to benefit cancer sufferers by means of any of the agencies
which have been employed in animal experimentation. Nevertheless, the
fact remains that a variety of preparations have been used in the human
clinic. The various types of preparations may be satisfactorily grouped
under four classes, namely:
1. The crystalline salts of selenium.
2. Selenium in colloidal solution.
3. Other metals in colloidal solution.
4. Compounds of metals with organic radicals.
These substances have been administered by injection or by the mouth.
In the case of injection, the injections have been made either into the
subcutaneous tissues, intramuscularly, or intravenously, or finally,
directly into the tumors. Before passing to a further consideration
of this subject in detail, it may be well to recall the fact that in
the experimental tumors of animals, no matter what preparation has
been used, it has been possible to accomplish therapeutic effects only
by the use of relatively enormous doses of the medicament, of doses,
in fact, which were scarcely lower than the lethal dose. Certain
experimenters have noted that smaller doses actually stimulated the
growth of the tumors. In the second place, it has almost invariably
been found necessary to administer the treatment intravenously,
inasmuch as the other modes of administration failed of therapeutic
effect. It is quite apparent that a procedure in human beings in any
degree analogous to that pursued in animals is entirely impossible. The
doses used, with one notable exception to be subsequently mentioned,
have invariably been relatively small. Hence it is apparent at the
outset that at least one fundamental condition of success in the
treatment of animal tumors has been necessarily excluded in the
clinical application.
The salt used by Wassermann is not stated in his original publication.
Wolff[281] speaks of it as a sodium salt, whereas Keysser says that it
was a combination with potassium cyanid. In only one instance, as far
as I am aware, has the sodium salt been used therapeutically in human
beings. Delbet[282] states that he employed this salt intravenously
in one case, and that its use was shortly followed by death.
Unquestionably the salts of selenium are very much too toxic to be used
in this way.
[281] Wolff: Die Lehre von der Krebs Krankheit =3=:1913.
[282] Delbet, P.: Bull. de l’Assn. franç. pour l’étude du cancer
=5=:121, 1912; ibid. =6=:85, 1913.
The majority of those who have worked with selenium have used it in
colloidal form, either preparing it themselves or employing one of the
preparations put on the market by the pharmaceutic firms. Of the latter
the best known are the electro-selenium of Clin, and the Seleniol of
Couturieux. Of those who have made use of selenium in these forms
may be mentioned Cade and Girard,[283] Bougeaut and Galliot,[284]
Blumenthal,[285] Thiroloix and Lancien,[286] Delbet, Laurent and
Bohec,[287] and most extensively of all, M. Touche.[288] All of these
authors have described cases of malignant new growths of the most
varied character which were treated by these preparations.
[283] Cade and Girard: Bull. Soc. méd. d. hôp. de Lyon =11=:397, 1912.
[284] Bougeaut and Galliot: Clinique, Paris =7=:501, 1912.
[285] Blumenthal, A.: Jour. méd. de Bruxelles, 1912, =17=:325; Presse
méd. belge =65=:919, 1913.
[286] Thiroloix and Lancien, A: Bull. et mém. Soc. méd. d. hôp. de
Paris =33=:197, 1912.
[287] Laurent, M., and Bohec, J.: Med. Press and Circular =94=:461,
1912.
[288] Touche, M.: Bull. et mém. Soc. méd. d. hôp. de Paris =35=:451,
1913.
The results obtained are fairly concordant. The intravenous injection
of the preparation produces but slight disturbance. There is
leukocytosis, a moderate rise of temperature, and not infrequently
a chill. Otherwise the substance seems to possess no toxicity. The
effects produced on the tumors have almost invariably been described
as encouraging. Touche, who treated twenty-seven cases in this way and
has described each case in detail, states that under the treatment the
surface of the tumors, if ulcerated, became cleaner and healthier;
the tumors became softer; the rate of growth was arrested, and there
was relief of pain and of the accompanying functional disturbances;
often, too, there was a gain in weight and an improvement in general
well-being.
Touche concludes his article with the statement that “it is certain
that the effect is not curative but it is actually palliative.” Delbet,
on the other hand, states that he has seen no beneficial effects from
the use of colloidal selenium injected intravenously. In the discussion
on Delbet’s paper, Ledoux-Lebard states that he has observed nothing
from selenium further than the temporary improvement which is shown
by almost all cancer cases on the application of any new therapeutic
measure. In one or two instances the claim is made in the literature of
an actual cure of malignant growth through the use of selenium. Such,
for example, is the case described by Blumenthal. From the clinical
description this might have been a cancer of the tongue, and was judged
to have been such in view of the negative Wassermann reaction. No
microscopic examination was made. Arsphenamin was given. The patient
recovered. It is clear that instances of this type cannot be accepted
as beyond criticism, and it is safe to say that nothing more convincing
in the way of actual cure is offered in the rather voluminous
literature on the use of selenium.
Numerous compounds of selenium, some of them claiming to circulate in
colloidal form, have been described, and have been put on the market
for use in malignant disease. Such are Walker’s sulpho-selene, and
selenio-vanadium, which has been prepared in the form of an ointment by
Schering and Glatz. These preparations lay claim to the same palliative
effects which have been previously described for colloidal selenium.
Of the other metals in colloidal form, chiefly silver and copper have
come into use. Colloidal silver was first recommended for malignant
growths by Vogel. It is obtainable on the market in proprietary
form under the name of fulmargin, and also as electrargol. Recently
Rohdenburg[289] has made a careful study of the effects of colloidal
silver in experimental and in human tumors, and finds that they have
no value. Colloidal copper has been used in recent times for the same
purpose by Gaube du Gers and by others. I have recently examined the
effects of colloidal copper on malignant tumors in man, and have been
unable to find that it has any therapeutic value. Furthermore, a study
of the distribution of the copper in tumors obtained at operation or by
necropsy from individuals so treated failed to show that the copper had
been deposited therein.
[289] Rohdenburg, H.: J. M. Research =26=:331, 1915.
Finally, preparations similar to those used by Werner and by Caspari in
animals have also been used in human beings. In these cases also the
authors have been able to record palliative effects on the tumor, but
in no instance cures.
We have seen that it has been quite impossible to duplicate in human
beings the therapeutic technic employed in animal experiments. We
have seen further that the use of a modified technic in animal
experimentation has never been productive of favorable results even
at the hands of enthusiastic adherents. In striking contrast to these
conclusions are the observations made in human therapeutics. For
every type of preparation described in the preceding paragraphs, the
claim has been made practically without exception that it exercises a
markedly beneficial effect on malignant diseases in the human being.
Not only are the subjective symptoms alleviated, but also the tumors
appear to become cleaner and softer; the rate of growth is retarded;
necrosis and metastasis are prevented, and inoperable tumors become
operable. How are we to interpret these observations? How are we to
explain the fact that they are the almost invariable accompaniment
of the most diverse methods of treatment? I have already quoted the
statement of Ledoux-Lebard that every therapeutic novelty appears to
exercise a favorable effect on cancer cases. The same fact has been
observed in a variety of other diseases, such as locomotor ataxia.
In order to arrive at a safe and reliable estimate as to the value
of any new or experimental procedure in cases of cancer, it seems
advisable to accept certain definite therapeutic criteria by which the
cases are to be judged. In the absence of such a method, alterations
in symptoms which are actually of no real value or importance receive
undue emphasis. The natural course of the disease is associated
with such fluctuations that a sanguine therapeutist can gain some
encouragement from even the most hopeless cases. Hence it follows that
every mode of treatment has found adherents. The market is flooded
with cancer drugs, and cancer charlatans flourish in the most highly
educated communities. Unfortunately, even well trained, honest and
reputable physicians have fallen victims to this fallacy, and have
lent their names to the support of modes of treatment which in reality
produce no determinable effect on the natural evolution of the disease.
It was the desire to combat this unfortunate tendency which led me
some time ago to attempt to establish a reliable set of criteria of
therapeutic effects in cancer. These were embodied in an article[280]
which appeared two years ago, and I may be here permitted to quote them
in extenso:
CRITERIA OF THERAPEUTIC EFFECTS
In determining the effects of any given mode of treatment on a tumor,
a variety of criteria may be relied on. Circulatory changes in the
tumor, the relief of pain and the restoration of a secondarily
impaired function are certain of the criteria on which stress has
been laid by the majority of observers in the past. Important as are
these criteria in determining the progress of purely inflammatory
processes, it is unquestionable that their value in judging of the
effects of therapeutic methods when applied to malignant disease is
open to criticism. It is a curious and interesting fact that almost
every therapeutic claim made in recent years in connection with
cancer has included among its virtues the relief of pain. This is
true of vaccination with cancer tissue, of Hodenpyl’s method and of
many others. In view of this very general effect, not much stress
can be laid on this symptom, and it is probably fair to assume that
in the great majority of these cases the result is in no small
measure psychic. The improvement of function is also largely a
subjective phenomenon, and as such requires most careful criticism.
Osler relates that he has known a patient with gastric cancer to be
relieved of digestive disturbances and to gain 18 pounds in weight as
the result simply of the visit of a sanguine consultant who denied
the presence of a tumor. Improvement in the ability to chew food, to
articulate words or to move a limb are phenomena familiar to those
who attempt to treat cases of cancer. The victims of this disease
seem to be in a very high degree “suggestible” and impressionable and
respond nobly to every therapeutic effort.
Circulatory changes in tumors offer an interesting group of clinical
symptoms. The observation has often been made, especially in
ulcerated new growths, that treatment is associated with swelling,
peripheral hyperemia, and an altered character of the discharge.
In spite of the fact that there is no reasonable relationship
between this congeries of symptoms and the actual cure of the tumor,
they generally receive considerable emphasis and are cited as an
indication of the specific local action of the agent employed. It
is also true, however, that the growth may continue to advance in
spite of their presence. It is of some importance to inquire into the
mechanism which produces these circulatory changes and into their
clinical interpretation. It is a well known fact that many drugs,
when introduced into the body either by the mouth or through the
skin, are excreted not only by the normal channels of elimination,
such as the kidney or the intestine, but also from such ulcerated
surfaces as may be present on the body. This is easily shown to
be true, for example, of certain of the anilin dyes, which, when
introduced by way of the veins, produce an intense discoloration
of the dressings over ulcers. It is likewise true of certain of
the metals, such as arsenic. In order to understand the series of
events previously enumerated it is therefore only necessary to
assume that the therapeutic agent is excreted from the ulcerated
surface of tumors. If an irritant, it will tend to produce hyperemia
of the margins of the ulcer, and an increase of the secretions. If
an astringent, however, it may produce just the opposite of these
effects. Such a result, however striking, is purely accidental, and
has no necessary bearing on the growth or destruction of the tumor
itself. It constitutes a symptom on which no reliance should be
placed.
Excluding from consideration all of these secondary factors, we may
conclude that the observation of the size of the tumor itself is
the sole criterion on which we can place reliance in judging of the
effect of therapeutic measures. This implies, in the first place,
that a tumor must be accessible to fairly accurate measurement.
Tumors of the uterus, for example, and intra-abdominal growths
will only exceptionally fall into this class. In the second place,
indirect evidence of a decrease in the size of tumors, such as is
afforded by the increased permeability of obstructed passages, as
in the case of tumors of the esophagus, pylorus or intestine, must
be accepted only with great reserve. Remissions in the obstructive
symptoms characteristic of such tumors are a frequent feature of
the normal evolution of the clinical history of such growths. The
relief of obstruction, however, may be due either to necrosis of the
obstructing portions of the tumor, while the remainder continues
to grow progressively, or to a relief of the accompanying muscular
spasm. Finally, evidence of decrease afforded by the roentgenogram
is not sufficiently exact in most cases to afford ground for so
important a conclusion as that at present in question.
Not only must there be unquestionable evidence, however, of the
diminution in size of the tumor, but this diminution must be of a
kind not ordinarily attributable to the natural evolution of the
tumor.... It is safe to say that multiple tumors offer enormous
difficulties in the matter of interpreting therapeutic results. At
present we have in the wards of the hospital a patient with multiple
metastatic carcinomas of the skin. For several months we have at
intervals made accurate measurements of certain of these tumors
and have found that some have undergone retrogression, others have
entirely disappeared, while still others have continued to grow
steadily. In the case which afforded the ascitic fluid used in
Hodenpyl’s experiments, many of the lymphatic metastases underwent
complete retrogression, while the metastatic process in the liver, as
was demonstrated at necropsy, increased progressively, and ultimately
almost destroyed that organ. Thus, in multiple carcinosis, the
retrogression of individual nodules is no indication that therapeutic
intervention has produced an improvement.
I shall not delay to emphasize those variations in the size of solid
tumors which accompany hemorrhage and its absorption, edematous
swelling, necrosis in the depths, and other familiar factors which
clinically simulate, or induce, the softening and the reduction
that are so often attributed to therapeutic interference. But it is
important to draw attention to a similar feature in that type of
superficial epithelioma known as rodent ulcer. These new growths not
infrequently advance at one point of the periphery, while they recede
at another, and thus cicatrization and contracture may simulate a
partial recovery. This effect is due in part to alterations not
in the growth itself, but in the accompanying ulcerative process.
The secretions from the growths, especially if confined under
dressings, may have eroded and destroyed the surrounding skin, and
it is tempting to interpret a recession of the associated ulcerative
disease as an indication of a favorable effect on the new growth.
It is unquestionably this aspect of rodent ulcers which plays so
generously into the hands of the numerous venders of nostrums for
this disease.
_In brief, the demonstrable reduction in size of a tumor, of a kind
not to be attributed to the natural processes of evolution of that
tumor or of its associated lesions, is the one essential feature of
effective therapeutic intervention._
When the various methods of treatment which have been discussed in
this paper are judged by the standard advocated above, it is apparent
that none of them can lay claim to therapeutic effectiveness. The
modifications of the disease attributed to them are modifications which
occur spontaneously in a very large proportion of cases as a result
of the natural evolution of the disease process. This is a fact which
cannot be too strongly emphasized. Owing unfortunately to the hopeless
character of cancer, men are not prone to study with care all the
lesser changes which the disease and the patient present under ordinary
conditions; but when a “cure” is under investigation, the patient and
his medical attendant note every apparent improvement with painstaking
attention and enthusiasm. As a result, some evidence of improvement in
treatment is entered on the books.--(_From The Journal A. M. A., April
17, 1915._)
THE DIRECT SALES COMPANY
During the past four or five years, The Journal has had inquiries
similar in effect to this, just received from Dr. E. P. Jewett of
Gardner, Mass.:
“Will you kindly inform me regarding a drug manufacturing company
by the name of the Direct Sales Company, Buffalo, New York? Are
their products standard and reliable so far as you know?”
The Direct Sales Company, Inc., Buffalo, has, according to its
letterhead, the following officers:
Geo. J. Dotterweich, President and Treasurer,
C. K. Dotterweich, Vice-President,
Louis B. Seufert, Secretary.
This concern circularizes physicians and emphasizes that it sells
“Only by Mail.” It also features a “profit sharing rebate” scheme,
whereby purchasers receive a coupon representing 10 per cent. of the
invoice value of each purchase. After $100 worth of merchandise has
been purchased the $10 worth of coupons when “presented for redemption
at one time” will be “honored as cash”--presumably on the purchase of
additional goods.
The Direct Sales Company catalogues have for some years, carried a
guaranty, which reads, in part:
“We absolutely guarantee all preparations to be in exact accordance
with the National Pure Food and Drugs Act, June 30, 1906.
“We also absolutely guarantee all preparations bearing our label to
be equal, if not superior, to any on the market.”
In one of the Quarterly Bulletins of the State Board of Health of New
Hampshire, issued last year, this paragraph appeared:
“The Direct Sales Company, Inc., Buffalo, N.Y., is a pharmaceutical
concern which until recently has done business direct with New
Hampshire physicians. In two or three instances complaints have
been received by this department that the preparations sold seemed
to be lacking in potency. Some time ago a physician sent us a
specimen of codein sulphate tablets, one-fourth grain, concerning
which he was suspicious, admission being made that the price paid
was very much less than current quotations. The amount of codein
sulphate actually found per tablet proved to be but one-sixteenth
grain. Later on, having subsequently received a new lot from this
source, the same physician sent us a second sample, the composition
of which was found to be practically identical with the first.
Acting under the federal law, 500 lot packages of the following
preparations were next purchased of the company direct, the
analytical results indicating serious deficiency in every case, as
follows:
“Tablets salicylic acid, 5 grains ... 1.72 grains found.
“Tablets acetylsalicylic acid, 5 grains ... 2.31 grains found.
“Tablets acetanilid, 3 grains ... 1.88 grains found.
“Tablets codein sulphate, 1/4 grain ... 1/15 grain found.
“Tablets nux and pepsin No. 2, claiming pepsin 1 grain, extract nux
vomica, 1/10 grain, found to have a gross average weight per tablet
of only 1.17 grains, 0.54 grains of which was represented by sugar
and other medicinally inert material.
“Tablets Infant’s Anodyne (Waugh) showed serious discrepancy from
formula.”
The Bulletin added the statement that, as the company could not be
reached under the New Hampshire laws, the federal authorities were
appealed to. The result of this appeal appeared in _Chemical Supplement
54_, issued Aug. 21, 1918, by the Bureau of Chemistry of the U. S.
Department of Agriculture. This government bulletin contained Notice
of Judgment No. 6193, which describes cases of adulteration and
misbranding of some of the drugs put out by the Direct Sales Company.
Briefly, it may be said that some 2 grain acetanilid tablets sold by
this concern were found by the government chemists to contain, roughly,
about 1-2/3 (1.61) grains; some 1/4 grain calomel tablets were found
to contain only about 1/6 (0.163) grain; some 1 grain quinin sulphate
tablets were found to have only about 2/3 (0.63) grain; some 2-1/2
grain salol tablets contained only about 1-1/3 (1.39) grain; some 5
grain sodium salicylate tablets contained less than half that amount
(2.32 grain). In addition, the federal chemists found that some Elixir
of Iron pyrophosphate Quinin and Strychnin (_Elix. Ferr. Pyrophos.
Quin. et Strych. N. F._) fell considerably below the standard of
strength laid down by the National Formulary by having less than
one-eighth the amount of quinin sulphate which the official standard
calls for, and only about one-fifth the amount of sugar, saccharine,
which is not a normal ingredient of the official preparation, having
been substituted for part of the sugar. The chemists found, too, that
some hydriodic acid sold by the same concern, instead of containing, as
the label declared and as the United States Pharmacopeia requires, 1
per cent. of absolute hydriodic acid, contained less than one half of 1
per cent. The Direct Sales Company pleaded guilty in this case and was
fined $700.--(_From The Journal A. M. A., Sept. 27, 1919._)
DISCOVERIES AND DISCOVERERS
In spite of the wonderful achievements of modern science, it seems
impossible to get the public to think in scientific terms. This is
doubtless due to a fundamental weakness in our educational system.
The tendency still is to think in terms of the eighteenth century
rather than of the twentieth. Many times The Journal has been chided,
even by its friends, for failing to take seriously preposterous
claims made for alleged discoveries in medicine by well-meaning but
self-deluded enthusiasts or by shrewd and conscienceless charlatans.
Far too often the attitude is that any alleged discovery in medicine,
no matter how bizarre or how humanly improbable, should be taken up
in all seriousness and subjected to the tests of modern laboratory
methods. It was only a few years ago that a quack of unsavory
antecedents brought forth an alleged cure for consumption--a disease
that for years has been the subject of study by the best brains in the
world--and a medical college spent thousands of dollars “investigating”
the “cure,” thereby giving it a standing that it would never have
received otherwise and incidentally obtaining for the school an amount
of publicity that may or may not have been desired. As The Journal
said at the time, it would have been just as pertinent for a body of
astronomers to determine by scientific methods whether or not the moon
is really made of green cheese.
The point we would make is that the strides made by modern science
have practically eliminated the possibility of men without training
or special knowledge evolving any epoch-making discovery. In this
connection an editorial in the _Scientific American_ of recent date,
dealing with the mechanical sciences rather than the medical, is well
worth quoting in part. The editorial discussed the “Garabed” incident.
“Garabed,” as Our readers know, was a name given to a device which one
Garabed T. K. Giragossian claimed to have developed and which, so far
as could be learned from the generalities in which Mr. Giragossian
indulged, would take energy out of the cosmos and transfer it directly
into mechanical motion. Mr. Giragossian would give no details regarding
his “engine,” but was so able to hypnotize Congress into a belief that
he had something worth looking into that it passed a joint resolution
calling for the appointment of five scientists to pass on the claims
for Garabed. The investigation proved, as might have been expected,
that the thing was unsound in principle and nonoperative as a device.
The methods by which Garabed was brought before the public savored
strongly of those used by quacks in the medical world, the one
difference being that Giragossian was apparently perfectly sincere
and unequivocally honest. The point that we bring out, however, and
which, as we have said before, was so well expressed by the _Scientific
American_, is the utter futility of wasting the time of scientific
men on alleged inventions or discoveries by men without training
who substitute secrecy and glittering generalities for facts and
accomplishments. Quoting the _Scientific American_:
Scientific discovery, once an open field for all comers, is today
becoming more and more a matter calling for the most intensive
special qualifications. As the body of human knowledge broadens and
deepens, it becomes increasingly difficult to make any material
addition to it. Any one undertaking such a task must of necessity
bring to it a long and careful training, acquired either in the
refined atmosphere of the laboratory, or in the rougher school
of close contact with the operation of apparatus constructed by
those who have already qualified. In particular, he must possess a
carefully developed power of making accurate observations and drawing
correct conclusions. It is rather the habit to point to men like
Edison and Maxim in refutation of these necessities; but they are not
to be so refuted. These men are examples, raised to the _n_th power,
of the great inventor who has qualified in the University of Hard
Knocks and Long Experience.
On these grounds, when a man comes before us in the self-assigned
rôle of a great inventor, it is incumbent upon him to answer, not
necessarily the bald question “Who are you?” but certainly the more
searching one, “What are your qualifications to undertake this
work?” Only by his answer can we decide whether he possesses a
competence deserving of attention, or is but a dilettante playing
with fire. Yet this obligation was one which Mr. Giragossian, far
from meeting, did not even appear to comprehend. To every effort to
ascertain his qualifications he replied in the same terms, that he
was an honest man, and could prove it by letters from his technically
nondescript collection of friends and sponsors. The very fact that
more than personal integrity is necessary in a man who would unravel
the secrets of the creation of energy appears to have escaped his
comprehension.
The fundamentals thus stated apply with equal force to the sphere
of medical discovery. At the time when medicine was pure empiricism
it was not only possible but also probable that the medicinal value
of certain products or combinations of products might be stumbled
on by those untrained and unskilled. That time has passed. Today,
while it is not impossible, it is so improbable that there is no
justification in taking up the time of scientific men in investigating
alleged discoveries by men who are utterly lacking in the fundamental
qualifications needed for the study of the complex problems of human
pathology.--(_Editorial from The Journal A. M. A., Aug. 10, 1918._)
“DRUG REFORM”
As It Appears to the Cleveland Medical Journal
The matter which follows appeared originally as an editorial in the
_Cleveland Medical Journal_, November, 1915. It expresses, we believe,
the attitude of the thinking physician toward the subject discussed:
Physicians have come to the realization that drugs are as a two-edged
sword--under proper conditions, striking against the disease;
otherwise, against the patient’s health. The first condition for their
proper use is adequate knowledge of their composition and purity; of
their actions and malefactions; their field and limitations. Slowly
and painstakingly--sometimes painfully--this scientific knowledge has
been gathered, is still being gathered, by chemists and pharmacists,
pharmacologists and clinicians, with increasing thoroughness, care and
discrimination.
Where wisdom fears to venture, unwisdom and cupidity find ample room.
The wise physician knows that there are ills that drugs cannot cure;
that drugs generally only aid or relieve; and that to obtain even
this aid efficiently and safely, the existing scientific knowledge
is none too great. Not so the unwise. He who sees in disease only a
name, to him a name is a sufficient cure. Let there be a mixture with
a convenient and suggestive name and a pleasant taste, a compendious
index of diseases and symptoms--and a lively imagination--and the cure
is accomplished. Few things could be easier, and few more false. It
is not surprising that the “man on the street” should fall into these
errors; it is sad that any physician should be misled by the sophistry
of interested drug vendors.
Physicians have the moral obligation to instruct the public in matters
of health. Preaching before practice is of little avail. It behooves
the medical profession to make at least a reasonable effort to clean
its own house before it passes the broom to the public. Realizing
this responsibility, the American Medical Association some years ago
established its Council on Pharmacy and Chemistry. This Council is
strictly an educational agency--it collects and disseminates knowledge
about drugs, especially those drugs that are advertised to physicians
and that are not described in the legal pharmacopeias. Physicians are
thus put in a position to discriminate. Many have done so; others will,
a few may never see the light on this earth.
Journals can no longer claim that they mislead their readers in good
faith. Some--the _Cleveland Medical Journal_ among the first--have
frankly acknowledged their obligations, and sacrificed a lucrative
income from advertisements; others are still occupied in compounding
the matter with their conscience. Manufacturers are in a similar
position. Those who are on the side of scientific progress--or to put
it materially, those who realize that honesty is the best policy--are
taking the opportunity to separate themselves from the dishonest and
ignorant.
Altogether, the medical profession may safely advise the public on
the subject of drugs without laying itself open to the charge that it
preaches what it is unwilling to practice.
Meantime, the public itself has had a somewhat similar awakening. The
progress of the profession has necessarily spread more or less to the
laymen. All sorts of educational agencies have been working to convince
the public that individual and national health is too precious an asset
to be entrusted to any quack who may spell his praise in printer’s
ink. Legislators have passed food, drug, and antinarcotic laws which
have aroused interest and discussion. Even the “drugless cults” have
somewhat offset their harm by causing the public to reflect that
drugging is not a panacea for all ills. All this has not been without
effect. The public is in a receptive mood; it is not convinced, but
wishes to learn. Legislators are prepared to follow public opinion. The
purveyors of patent medicines are watching events.
What, under these conditions, should be the attitude of the medical
profession? Plainly, it should continue to be what it always has
been: to stand aggressively for the protection of the public health,
without any compromise. In doing so, it is true, physicians will
expose themselves to the imputation of selfish motives. Selfishly
commercial minds cannot or will not understand the unselfish ideals
of a profession--that is their loss. Physicians, however, must be
careful not to give a semblance of reason to the charge; for that would
diminish the effect of their attitude. They must confine themselves to
informing the public of the facts; and to guarding the health of the
public at large, and of their own patients in particular.
No one, in a free country, can force a diseased individual to seek
effective treatment or prevent him from using an ineffective treatment,
unless his disease imperils the health of others. At that point, and
not before, the government can and should take personal measures.
However, it is a well recognized function of the government to protect
individuals against their own ignorance. It does this when it forces
the child to go to school; it does this when it places the swindler in
jail.
On exactly the same principle, the government has the right and the
duty to protect the uninformed public against the flagrant evil of the
patent medicine traffic--and the patent medicine traffic as now carried
on is a flagrant evil and series of evils. The government should
protect the public against advertisements that are framed to suggest
or create imaginary ailments, with their attendant miseries; it should
protect the public against being deluded by false promises of cure;
against the specious relief that merely hides the disease and blinds
the patient to its dangers; against drugs that may and do work positive
harm; against the veil of mystery that makes these abuses possible.
The individual layman cannot protect himself against these dangers,
and has a right to expect that the government will prohibit the
indiscriminate sale of any medicine that may be harmful to him. He has
a right to expect, when the government permits the sale of a patent
medicine, that the medicine will do him no harm; just as he has a right
to expect that any physician whom the government permits to practice,
should be competent.
These are some of the reasons why physicians oppose patent medicines
as they are now exploited; and for these reasons, physicians should
take an absolutely uncompromising attitude, and use every opportunity
to educate the public. The patent medicine interests naturally try
to obscure the issue. By the art in which they are so skilful, they
aim to suggest to the public that physicians are opposed to patent
medicines, in order to drive patients to their offices. They “forget”
to mention that physicians have never conducted a “campaign” against
really efficient preventive public-health measures, no matter how many
prospective patients were involved. No physician has ever refused to
give diphtheria antitoxin because this would diminish the number of his
visits. A short memory is a very convenient asset for self-interested
persons. It is not so convenient for the public--but it is all too
frequent. Physicians must, therefore, make it plain that their stand is
not against patent medicines, but for the protection of the health of
the public.--(_From The Journal A. M. A., March 4, 1916._)
DRUG THERAPY: THE FALLIBILITY OF TEXTBOOKS
Until very recently, we were compelled to acknowledge that little,
if any, progress was being made in internal medicine so far as drug
therapy was concerned. Everybody knows of the progress made in other
branches--in bacteriology, in pathology, in biologic chemistry,
in surgery, in etiology and in application of technical methods
to diagnosis. Recently, however, pharmacologic research and the
application of scientific methods in the study of the physiologic
action of drugs are resulting in definite, positive progress. An
important lesson, incidentally learned through this scientific
investigation, is the fallibility of the drug therapy described in
textbooks. The explanation is, of course, that many of these textbooks
are mere compilations containing false statements, unproved theories,
and unverified clinical evidence representing the guesswork of ancient
uncritical observers. Many drugs have been, and still are, vaunted in
textbooks as valuable in a variety of conditions, whereas scientific
investigation and controlled clinical observation have proved them to
be totally worthless; others are proving to be of value in an extremely
limited number of conditions. The sooner writers of textbooks realize
this fact and enter into the spirit of the new era, the better for
the public and for scientific medicine.--(_Editorial from The Journal
A. M. A., May 27, 1916._)
THOMAS WEBSTER EDGAR
Tired Rabbits for Diabetes; Ring-Tailed Monkeys for Sex Stimulation
During the last two or three years The Journal has received inquiries
regarding one Thomas Webster Edgar, M.D., of New York City, first,
relative to his alleged treatment for diabetes and more recently about
his “monkey gland” treatment for sex stimulation. Here is one from a
physician in Washington:
“Have you any knowledge of the efficacy of a serum made from the
pancreas of rabbits for the relief or cure of diabetes? It is made
by Dr. T. W. Edgar of 766 West End Ave., New York City.”
And this from a layman in Pennsylvania:
“Last year there was published in the _New York_ Herald an account
of the new treatment for diabetes in which a serum was injected in
the veins and as a result it was claimed that over sixty-five per
cent. of the treatments made were successful. The account further
stated that they proposed to establish some sort of a sanitarium in
New York City used especially for the treatment. The writer having
mislaid the account, wrote the _New York Herald_ as to the doctor
who had charge of it and in return was given the name and address.
Dr. Edgar in a letter under date of last year stated that the cost
of the treatment was $300.00, payable beginning of the treatment,
and he gave very little information as to the success of it, with
the exception that if the treatment did not give the desired effect
after the end of three months, it would be continued without any
further cost. The writer wrote and asked him the names of one or
two of the patients who had been cured, because it seemed rather
unusual that if the treatment were a success, it was necessary for
a patient to pay the cost of the treatment in advance. To that
letter I have never received a reply.”
While a physician from Illinois writes:
“I am enclosing a clipping from a Chicago paper relative to
Dr. Thomas Webster Edgar of New York and his operation for
transplanting the glands of ring-tailed monkey. I note that he is
a member of the New York County Medical Society! What is there to
this? I have seen no mention of these wonders in _The Journal_.”
Thomas Webster Edgar was born in 1889. The records show that he was
graduated in medicine by the University and Bellevue Hospital Medical
College in 1913, and was licensed to practice medicine in the State of
New York the same year. In March, 1919, an article by T. Webster Edgar
appeared in the _New York Medical Journal_ on “Diabetes Mellitus.” In
this Edgar gave a theory of the cause of diabetes mellitus and stated
that he had “treated successfully, twenty cases of definite diabetes.”
In the article he spoke positively of the successful results he had
obtained by the “intramuscular injections of my diabetic serum.” No
information was given regarding this serum except that he mentioned
vaguely that it was “prepared from normal blood after the animal is
exercised to the point of fatigue.”
[Illustration: Photographic reproduction (reduced) of a few of the
newspaper items that appeared in various parts of the country regarding
Thomas Webster Edgar’s alleged serum for diabetes.]
A few days after the appearance of this article in the _New York
Medical Journal_, newspaper articles appeared regarding a cure for
diabetes perfected by “Dr. Thomas Webster Edgar, 766 West End Avenue,
New York City.” According to these reports, Edgar said:
“I tried the blood of rabbits and found what I wanted. In obtaining
the blood I first put the rabbit upon a treadmill and keep it there
until it reaches a stage of fatigue. Then I draw the blood, and
after heating it to 60 degrees centigrade separate the corpuscles
from the serum. When the serum has been treated after the method I
have discovered, I inject it immediately subcutaneously.
“I have attained success in 65 per cent. of my cases and I have
had 100 cases. I do not say that the cure is infallible, but I am
now certain that it will work in most cases, particularly when
the patient observes the rules laid down and undergoes faithful
treatment.”
In April, 1919, a physician in Kansas wrote to Edgar at the request
of a diabetic patient asking for information about the “serum.” Edgar
replied that it would be impossible to send the physician any of
the serum for administration unless the “patient is willing to pay
me for the cost of same, which will be approximately the sum of $25.”
He stated further that, in a few months’ time, he hoped to be able to
manufacture the serum in larger quantities which would “more than cut
the expense in half.”
In the same month a layman in Chicago who read the newspaper story
wrote to Edgar and asked for details regarding terms and the
arrangements that would have to be made to take the “treatment.” Edgar
replied that he expected to be in Chicago in a few weeks’ time and
would see the man in consultation with his regular physician, that
he would administer the first injection and give instructions to the
physician as to subsequent injections. Edgar added:
“My custom is to have all fees paid in advance and my charge is
$200.00 by certified cheque or money-order.”
A layman in one of the smaller cities of New York wrote to Edgar in
May, 1919, and received a reply from Edgar’s secretary stating that
the treatment extends “over a period of three months, cost $150.”
He was also told that the serum could be sent to his physician for
administration “for the sum of $25 prepaid by money-order.” The letter
closed with the statement that Edgar “has been very successful with the
serum.”
[Illustration: Photographic reproduction (greatly reduced) of small
portion of the publicity that has been given to Edgar relative to his
operation for “sex stimulation” by the transplantation of the glands of
ring-tailed monkeys!]
A layman in South Carolina who wrote to Edgar in June, 1919, was told
that the treatment as administered by Edgar “extends over a period of
two months; fee $300” and that if he wanted the serum administered by
his own physician the cost would be “$50 prepaid.”
In May, 1920, Edgar had another article on diabetes, also in the _New
York Medical Journal_. In this, too, he refers to his serum in the
following words:
“In conclusion I may state that I have been able to produce some
rather startling results by the use of my serum, which is prepared
from the blood of rabbits after they have undergone a series of
maneuvres capable of activating the various internal secretory
glands to increased action. The serum contains the internal
secretions in hormone form.”
Gradually the newspaper publicity on Edgar’s diabetic “serum” died
down. Then, in November, 1920, there appeared--again in the _New York
Medical Journal_--an article by Edgar on “Sterility, Sex Stimulation
and Endocrines.” Edgar there stated that he wished to place himself
“on record as being interested in sex stimulation” and that he wanted
to notify the profession that he had another serum which he was using
“with success in the treatment of this condition.” Thus:
“... I feel entitled to state that I have a distinctly beneficial
serum for the alleviation of presenile and senile deficiency; and
that my product is capable of producing a new lease of life in
those whose functions have been reduced to a minimum.”
How long Edgar has been featuring his “serum” for “sex stimulation”
it is difficult to determine, but during the last year the newspapers
have carried sporadic reports of alleged remarkable results produced
by “Dr. Thomas Webster Edgar of 766 West End Ave., New York,” through
the transplantation of the “interstitial gland” taken from “a special
species of orangoutang.” A layman who wrote Edgar some months ago
regarding this “gland implantation” received a letter from Edgar’s
secretary stating that the treatment “has been most successful in
all cases” and assuring him that “the experimental stage had been
passed, and the operation is advised in all cases presenting symptoms
of presenility or age.” A week later the same man received a letter
written by Edgar himself in which he reiterated the claim that all
of the operations had been successful. Edgar added that he was now
treating all cases “by operation instead of the serum,” and that
“the fee for operation is $500, inclusive of the sanitarium,” the
patients remaining in the “sanitarium” “for from two to three days.”
A month or two later the prospective patient received another letter
signed, “Thomas Webster Edgar, M.D.,” assuring him that “the effect is
permanent, and does not wear off. No ill effects can possibly result.”
Commencing, Oct. 1, 1921, a series of sensational articles appeared
regarding one of Edgar’s alleged monkey gland implantations performed
on an individual described as “one time lawyer and then a writer.”
These articles purport to be written partly by one of the newspaper
staff, partly by the man undergoing the “operation” and at least
one by Thomas Webster Edgar. The material is played up in the style
typical of yellow journalism. In addition to repeated pictures of the
individual who is being operated on, there also are given pictures of
Thomas Webster Edgar and one of his “ring-tailed monkeys.” Doubtless
the “story” has sold many newspapers. Its sensational character, the
element of mystery and above all its sex slant will appeal to that
large class of newspaper readers that hunger for stuff of this sort.
Doubtless, too, it has proved a large advertising asset for Thomas
Webster Edgar.
The statement that appears in the series to the effect that Edgar “is a
member of the County Medical Society of New York” is incorrect. Edgar
is not a member.
The further newspaper claim that Edgar is “an authority on glandular
transplantation” should also be accepted with reservations.
“Authorities” are created with ease in the pages of newspapers. Edgar
may possibly be termed an authority in a newspaper or, shall we say,
Pickwickian sense.--(_From The Journal A. M. A., Oct. 15, 1921._)
The Journal Receives a Letter Denouncing “Medical Clerks” and
“Biased Sceptres”
The Journal recently published in this department some inquiries
regarding Thomas Webster Edgar, M.D., of New York City, relative to
some alleged serums that Dr. Edgar had developed for diabetes and sex
stimulation, respectively, and relative also to the newspaper publicity
given Dr. Edgar in connection with the alleged transplantation of
glands from “ring-tailed monkeys.”
We are in receipt of a letter signed, “Thomas Webster Edgar, M.D.,” and
reading as follows. It is given _verbatim et literatim_:
“_Gentlemen_:--I have read with great interest your editorial
regarding the publicity given my work in metabolism, and gland
implantation.
“Your pseudo, expose, and distinctly libelous
insinuations are unjust, and they lead me to believe that you are
going to be called to account at a very early date.
“My profession is the practice of medicine, and the policy of my
practice is not controlled by the editorial department of the
journal. I am progressive, and a firm believer that legitiment
medicine and surgery can not be practiced if the physician be
governed by a set of medical clerks, who disdainfully boast that
they control, and govern the healing art through out the breadth
of the land, with a sceptre that is biased and steeped in the
unadulterated commercialism of a certain medical clique.
“Aside from the fact that I am an associate editor on a medical
publication, it is disgraceful, as well as unjust that you have
written such an editorial with out first investigating the
therapeutic value of my serum, and implantation operation.
“The psychology of your editorial, only reflects on your editorial
department, and will tend to belittle some of the greatest surgeons
in the country.
“It may be to your advantage to know, that this very afternoon, I
was on the program with the following men.
“Dr. Lewis Gregory Cole--New York
“Dr. Charles H. Mayo--Rochester, Minn.
“Dr. John B. Deaver--Philadelphia
“Dr. Charles Peck--New York.
“My paper was entitled--Senility, its etiology and treatment
by gland implantation. I am sure the above mentioned gentlemen
are thoroughly ashamed of your actions in the matter, as well
as thoroughly disgusted with the baby like attitude you have
displayed. You have no sense of fair play, and if it is with in
my power to undue the wrong which you have wrought me, I shall
endeavor to vindicate myself in the eyes of the clear thinking
members of the profession.
“I sincerely trust you will publish this communication, in order
that my brethren shall understand and appreciate that your thrust
has not gone unnoticed.
“It is my hope that the various medical societies through out the
country, will call upon me to read a paper on my work, so that I
may be able to offer substantial evidence to the fact that you have
done me an injustice.
“Very truly yours,
TWE/AEL [Signed] “Thomas Webster Edgar, M.D.”
Dr. Edgar’s statement that he had been on the program with Drs. Cole,
Mayo, Deaver and Peck was sufficiently startling to prompt further
investigation. It was found that the program in question was that of
the annual meeting of the New York and New England Association of
Railway Surgeons. It was further found that Edgar’s name did appear on
some of the printed programs but not on others. It was rather naturally
assumed that the name had been put on the program before the officers
of this organization had seen the crude publicity to which The Journal
recently called attention. It was found, however, that after several
hundred programs had been printed about 150 more were needed and “in
the meantime, Dr. Edgar had come into the limelight” in his ring-tailed
monkey gland transplantation rôle and “was invited to read a paper on
the subject.” While he accepted this invitation the secretary of the
organization tells us that Edgar did not read his paper but, when the
paper was called, declined, saying it was time for him to be in his
office!
As for the rest of Dr. Edgar’s communication, The Journal
appreciates that courtesy is due “an associate editor on a medical
publication”--referring doubtless to the _Western Medical Times_.
Dr. Edgar’s pronouncement that “legitimate medicine and surgery can
not be practiced if the physician be governed by a set of medical
clerks” seems reasonable--if cryptic. But it is when he charges that
these “clerks” govern the healing art “with a sceptre that is biased
and steeped in the unadulterated commercialism of a certain medical
clique,” that he really shines. Whatever opinion one may hold of Dr.
Edgar’s ability to compound serums, surely no one can question his
skill as a mixer of metaphors. His reference to “sceptres” deserves
to be embalmed in every textbook on rhetoric with the classic of the
Hibernian statesman who passionately declared: “I smell a rat! I see
it floating in the air! But, mark you, Sir, I shall nip it in the
bud!”--(_From The Journal A. M. A., Dec. 3, 1921._)
GLYCEROPHOSPHATES
Physicians who prescribe on definite principles must often be puzzled
by the number and variety of glycerophosphates on the market. All
available evidence indicates that, as sources of phosphorus to the
animal organism, the glycerophosphates possess no advantages over the
ordinary inorganic phosphates.[290] The glycerophosphates are split
up in the intestine, and liberate inorganic phosphates. In this form
they are absorbed and utilized, if they are utilized at all. There is
no evidence that glycerophosphates have any pharmacologic action to
warrant the belief that they are of use as therapeutic agents. The
theory that organic phosphorus compounds are more readily assimilable
than inorganic compounds and hence a better means of introducing
phosphorus into the system is still kept alive in the promotion of
certain proprietary mixtures, in spite of the scientific evidence that
the organism can assimilate phosphorus quite as readily from inorganic
as from organic phosphorus compounds.[291] The glycerophosphates will
continue to be manufactured until physicians refuse to prescribe them.
A chemist in the “research laboratory” of a well known manufacturing
firm has recently given a rather interesting reason for the use of
glycerophosphates--from the manufacturers’ point of view. He is quoted
as saying: “On account of the instability of phosphorus in elixir of
phosphorus, nux vomica and damiana we have quite recently replaced
the phosphorus by glycerophosphates. Such a preparation is apparently
equally as effective, for we continue to have a great demand for it.”
This is doubtless a sufficient reason for the substitution from the
manufacturers’ point of view; but how about the patient, who, after
all, is the one to be considered? Is it not a matter of considerable
importance to the patient whether he receives phosphorus, one of
the most powerful drugs known, or the inert glycerophosphates? The
chemist’s statement seems to imply that it is not. It may be of
interest to recall that a member of the firm whose chemist gives
this “reason” for the use of glycerophosphates, in a recent address,
was rather severe in his condemnation of institutions of learning,
hospitals, etc., for their lack of cooperation with manufacturers: he
said that “they should welcome an opportunity to let any manufacturer
try out or test his products in their clinics, laboratories, etc.”
A test as to whether there is a difference between the action of
glycerophosphates and ordinary poisonous yellow phosphorus, especially
when the former are mixed with extracts of nux vomica and damiana,
would not be likely to appeal to many hospitals and laboratories as
a very promising field of research at this day since, as has been
stated, the scientific evidence at present available does not furnish
any warrant for the therapeutic use of glycerophosphates.--(_Editorial
from The Journal A. M. A., April 15, 1916._) [290] Organic Phosphorus
Compounds, Editorial, J. A. M. A. 40: 1958 (June 21) 1913. Marshall,
E. K.: The Therapeutic Value of Organic Phosphorus Compounds,
J. A. M. A. 44: 573 (Feb. 13) 1915.
[291] Marshall, E. K.: The Therapeutic Value of Organic Phosphorus
Compounds, J. A. M. A. 44: 573 (Feb. 13) 1915.
INFLUENZA VACCINES
With the appearance of the epidemic of influenza, reports began to
appear, chiefly in newspapers, as to new serums, vaccines, drugs and
other methods for checking and even for curing the disease. A few
samples of such as have come to The Journal appear in our Tonics
and Sedatives Department this week. In Massachusetts, Commissioner
E. R. Kelly appointed two committees to investigate the value of
influenza vaccines as a preventive agent and as a treatment of
the disease. The first committee, a special board for scientific
investigation, consisting of Dr. M. J. Rosenau, chairman, and Frederick
P. Gay and George W. McCoy, was appointed to consider the evidence
available on the prophylactic and therapeutic use of vaccines against
influenza. This committee presented the following conclusions:
1. The evidence at hand affords no trustworthy basis for regarding
prophylactic vaccination against influenza as of value in
preventing the spread of the disease, or of reducing its severity.
The evidence from the present epidemic, though meager, suggests
that the incidence of the disease among the vaccinated is smaller
than among the nonvaccinated. The board, therefore, concludes that
further experimental evidence should be collected.
2. The evidence at hand convinces the board that the vaccines
we have considered have no specific value in the treatment of
influenza.
3. There is evidence that no unfavorable results have followed the
use of the vaccines.
The second committee, known as the Special Board of Statistical
Investigation, consisted of Dr. George C. Whipple, chairman, William H.
Davis and F. C. Crum. This committee reported:
1. The weight of such statistical evidence as we have been able to
accumulate indicates that the use of the influenza vaccine which we
have investigated is without therapeutic benefit. Exceptional cases
where apparent benefit has resulted from the use of the vaccine can
be matched by other cases where similar recoveries have been made
without vaccination.
2. The statistical evidence, as far as it goes, indicates a
probability that the use of this influenza vaccine has some
prophylactic value.
3. There is also some evidence to the effect that other methods
of protection, such as open-air treatment and the use of proper
masks, are effective in protecting exposed attendants, and the
use of vaccine should not be taken as an excuse for omitting such
safeguards.
As a result, the following recommendations were made:
That the state encourage the distribution of influenza vaccine
intended for prophylactic use, but in such manner as will secure
scientific evidence of the possible value of the agent. The use of
such vaccine is to be regarded as experimental.
That the state shall neither furnish nor endorse any vaccine at
present in use for the treatment of influenza.
These reports are conservative, and offer to other health commissioners
and their communities a reliable guide as to procedures that should
be adopted before subjecting or trying out on the public any method
of prevention or treatment that may be offered. These matters are the
domain of medical science, and medical scientists of recognized ability
should be called on to make the decision.--(_Editorial from The Journal
A. M. A., Oct. 19, 1918._)
Serums and Vaccines
With respect to serums and vaccines in influenza, there are certain
simple facts and considerations that physicians will do well to keep
in mind at this times. The main point to keep always in sight is that
unfortunately we as yet have no specific serum or other specific means
for the cure of influenza, and no specific vaccine or vaccines for its
prevention. Such is the fact, all claims and propagandist statements
in the newspapers and elsewhere to the contrary notwithstanding. This
being the case, efforts at treatment and prevention by serums and
vaccines, now hurriedly undertaken, are simply experiments in a new
field, and the true value of the results cannot be predicted by any
one. Indeed, the exact results can be determined if at all only after a
time, in most cases probably not until the epidemic is past and all the
returns fully canvassed. Consequently, the physician must keep his head
level and not allow himself to be led into making more promises than
the facts warrant. This warning applies especially to health officers
in their public relations.
As to serum treatment, the only noteworthy new method so far is the
injection in severe cases of influenzal pneumonia of the serum of
patients who have recovered from such pneumonia.[292] The principle of
this method is rational; analogous procedures have given seemingly
good results in scarlet fever and other diseases; and the results
reported in influenzal pneumonia appear promising. Further trial
of this treatment under proper conditions consequently seems to be
warranted. It should be borne in mind, however, that McGuire and
Redden[292] made their observations in the declining phase of the
epidemic when the organism or organisms concerned appeared to be losing
virulence. For this and other reasons, the expectations as to what may
be accomplished by this method must be kept within reasonable bounds.
Influenza is a self-limited disease with variable complications and of
variable severity in different places, thus offering great difficulties
in the way of evaluation of different methods of treatment.
[292] McGuire, L. W., and Redden, W. R.: Treatment of Influenza
Pneumonia by the Use of Convalescent Human Serum: Preliminary Report,
J. A. M. A. =71=:1311 (Oct. 19) 1918.
At least two kinds of vaccine are in use in the hope that they may
have preventive effects. One consists solely of killed influenza
bacilli; it being extensively used in the East. We have as yet no
decisive figures as to its effects, but there is an impression that it
may have some value. The other vaccine is a mixed vaccine of the more
important bacteria in the respiratory tract in influenza, principally
pneumonococci, streptococci and influenza bacilli. It appears that
vaccines of this nature are in extensive use, but we have no evidence
that any benefit will be derived from them. To say that thousands
have been vaccinated with apparently good results means nothing at
all, simply because we are still in the midst of the outbreak, in
many places even in the earlier stages. How slender the basis of
this anti-influenzal vaccination when it is considered that the real
nature of influenza is still unknown! In any event, it will require
many carefully elaborated and controlled observations before anything
definite may be learned in regard to the effect of these vaccines,
and it is probably safe to say that nothing on which to rely in the
future can be learned from the indiscriminate vaccination now going
on. There is, therefore, no basis on which promise of protection from
vaccines may be made. They may be harmless, and they may or may not be
of preventive value.--(_Editorial from The Journal A. M. A., Oct. 26,
1918._)
INTRAVENOUS THERAPY
The intravenous administration of drugs is a new departure in therapy,
but one which is rapidly increasing in use. Among its reputed
advantages are that it is the quickest means of obtaining the effects
of a drug, the effects are obtained with a certainty not obtained by
other methods, and they are so marked that they cannot fail to impress
the observer. These advantages in many cases are apparent rather than
real; but even were they real advantages, they should not blind us
to the various and serious dangers which this method involves. The
technic, although not difficult, must be thoroughly mastered, or
undue pain, infection, air embolism, or even death may result. Such
accidents, however, are ordinarily easily avoided, and should be
considered quite inexcusable. More serious is the fact that the drugs
given intravenously reach the system, and especially the heart, in a
different manner and concentration from that to which physicians are
accustomed with ordinary methods of administration. Pharmacologists
have long practiced intravenous administration, when studying acute
effects of drugs, and they have observed that frequently the immediate
result of such injections is a prompt fall of blood pressure, not
obtained when the same drugs are given by mouth or even hypodermically.
This fall in blood pressure is commonly attributed to irritation of
the endocardium. It is usually of short duration, but is certainly
undesirable and sometimes may have serious results.
It has also been observed that several drugs, for instance, quinin and
potassium, depress the cardiac muscle when given intravenously much
more than when given in other ways. Furthermore, any substance which
tends to precipitate proteins must be injected slowly and with extreme
caution, or it will produce intravascular clotting and sudden death.
Deaths have resulted not only from a lack of knowledge of the technic
of intravenous therapy, but also from a lack of knowledge of drugs
which may be so administered. Sudden death has been reported following
the injection of an iron preparation containing peptone, and also
following intravenous injection of ether. Intravenous injections, while
sometimes superior to the slower methods, are distinctly inferior when
a continuous, rather than a sudden, action is desired. Drugs leave the
blood system with great rapidity, and therefore their action on the
circulation will cease promptly unless they are continuously supplied.
It would be undesirable to inject intravenously such drugs as iodids,
nitrites, iron or salicylates.
With these dangers and disadvantages in mind, it seems unwise to
resort to promiscuous intravenous medication until the effects of
this method have been studied in detail for the drugs employed, and
unless there are distinct advantages to be secured. This is the case
when an immediate action is necessary in emergencies, as in the use of
strophanthin for cardiac collapse, quinin in pernicious malaria, etc.,
or if the drug would be destroyed in the stomach or tissues as in the
case of salvarsan, or when the drug is not adequately absorbed by any
other channel, as in the case of epinephrin.
Intravenous therapy will be most securely advanced if its employment
is restricted to such well defined fields. These fields can be
satisfactorily determined only by a scientific pharmacologic study of
the action of these drugs when so administered in animals, as well as
in man, under conditions in which the results are carefully controlled.
The intravenous method is an impressive one, approaching in preparation
almost to that which goes with a surgical operation. The patient is
usually interested and impressed by this new, and to him, mysterious
method. There is a psychic element in his reaction to the injection
which is not a factor in his reaction to the same drug when given by
mouth. The intravenous injection of a complex mixture would appear to
be particularly reprehensible. Little is known, as has been stated,
of the results to be expected from intravenous therapy, even with
simple substances. The use of complex mixtures will without doubt react
against the proper use of the method.--(_Editorial from The Journal
A. M. A., Nov. 11, 1916._)
IODIN FUMES
One of the important factors connected with therapeutics as a science
is the method of administration of medicinal substances. Drugs
may be given by mouth, by hypodermic or intravenous injection, by
inhalation, by inunction or, less frequently, by the use of other
entrances into the body. In choosing a method, the physical characters
of the substance to be administered and the immediate effects of the
substance on the body tissues with which it may come in contact must be
especially taken into consideration.
These factors apply particularly in the case of substances like
iodin, arsenic, mercury or the biologic products in which the mode
of administration radically modifies the action. For some time,
manufacturers have urged substitutes for tincture of iodin, claiming
that their substitutes were free from the undesirable properties of the
tincture, and, at the same time, possessed special virtues which the
tincture could not possess. More recently, attention has been directed
to the administration of iodin in the form of vapor. The diffusing and
penetrating powers of gases have particularly attracted the attention
of therapeutists, since by this method drugs may be applied to rather
inaccessible portions of the body, such as the lining of the lungs,
the throat and the mucous membranes of the genito-urinary tract.
Furthermore, it has been asserted that iodin in the form of fumes has
increased combining powers, and is thus far more potent in effect than
iodin administered by any other route. There do not seem to have been
any adequate scientific investigations of the subject, however, until
the recently published results of Luckhardt and his collaborators[293]
at the University of Chicago. In their experiments, both on man and on
animals, accurately determined quantities of iodin were vaporized in a
special device, and the fumes applied to the skin. At the same time,
the tincture was applied to the skin of other persons as a control.
Iodin was also applied to the skin of dogs with hyperplastic thyroid
glands; and the effects on the gland, before and after administration,
studied. Dogs were also used to determine whether iodin fumes were
absorbed from the lungs. As a result of these investigations, which are
reported in great detail, it was found that iodin, when deposited on
the skin in the form of fumes, is absorbed. More iodin was recovered
from the urine, following the application of the tincture, than was
recovered following the use of the fumes. This result is explained
by the authors on the ground that probably more iodin was actually
applied, and that the iodin so deposited was held in combination with
the protein during the process of coagulation of the latter by the
alcohol of the tincture, leading to a state of continuous absorption.
It is probable, furthermore, that the iodin deposited on the skin in
the form of fumes is revaporized to some extent by the heat of the body.
[293] Luckhardt, A. B.; Koch, F. C.; Schroeder, W. F.; and Weiland,
A. H.: The Physiological Action of Fumes of Iodin, J. Pharmacol &
Exper. Therap. 15: 1 (March) 1920.
Most important were the effects of iodin administered intratracheally
in the forms of fumes. Iodin given in this way seems to be rapidly and
completely absorbed; but it was found that the administration of the
fumes of iodin by inhalation through the respiratory passages, even in
small quantities, is fraught with great danger. Such administration
induces dyspnea; and when it is given in large quantities, acute and
fatal pulmonary edema ensues within twenty-four hours. When respiratory
disorders are present at the time of administration, the fatal edema
supervenes very quickly. Thus far, no device designed to deliver fumes
controls the dosage.
It is interesting to consider, as do the authors, the fact that the
fumes of iodin have the same effect as those of two other halogens,
bromin and chlorin. The results of these experiments with iodin fumes
on the dog, as shown by necropsy findings, are practically identical
with those reported by military surgeons as found in soldiers gassed
with chlorin during the war.
The results of these researches are additional evidence as to
how scientific research may confirm or deny conclusions based on
empiric therapeutic observations. The work may well serve as a model
for similar experiments, now being made, on the therapeutic use,
intravenously, of such substances as nonspecific proteins or organic
preparations of toxic drugs. The patient should at least have the
chance that is afford him by preliminary experiments, scientifically
performed on animals in the research laboratory.--(_Editorial from The
Journal A.M.A., May 29, 1920._)
ITALIAN PHYSICO-CHEMICAL COMPANY
Many and various are the letters received by The Journal asking for
information about an alleged scientific organization in Italy styled
_l’Académie Physico-Chimique Italienne_. This Italian Physico-Chemical
Academy is operated from Palermo, Italy. Here is the scheme: Dr. John
Doe, an American physician receives an imposing-looking letter bearing
the Palermo, Sicily, postmark and addressed to “_Monsieur le Docteur
John Doe, Médecin_.” On opening the letter “_Monsieur le Docteur_”
finds that the “Council” of _l’Académie Physico-Chimique Italienne_
has nominated him “Honorary Member of this Academy” and furthermore
has bestowed on him “a First Class Medal for technical work and
scientific merit.” All this, “in consideration of your many dignities
and great learning.” Dr. Doe is told that as soon as he will write an
acceptance of this honor “in conformity with Section 19 and 22 of the
Constitution” he will be sent “the Medal, Diploma and all the other
documents relating to the title accorded.” The joker in the scheme lies
in the necessity for Dr. John Doe “conforming” with “Section 19 and 22
of the Constitution.” Here are the sections:
[Illustration: Reduced photographic reproduction of the stock letter
sent to American physicians by the Italian Physico-Chemical Academy.
The “joker” lies in the requirement around which we have drawn a line.]
“_Sec. 19._--The entrance fee to cover office and postal expenses,
including postage of diploma is 5 Dollars, and is payable once at
the admission to the Academy by special bulletin filled up, stamped
and signed.”
“_Sec. 22._--Those to whom medals are awarded and who wish to
possess them must pay for their coinage 10 Dollars as the Academy
does not, at present, possess the necessary funds for this
purpose....”
In short the whole thing means that if Dr. Doe is willing to send $15
in good American money he will receive in due time from the academy a
“diploma” and a gilt (not gold) medal.
About four years ago when the “Academy” seemed to be making a
particularly heavy bid for American dollars the member of The Journal
staff in charge of the Propaganda Department wrote to the “Academy,”
on his personal stationery, asking about the cost of membership in the
“Academy” and asking also for a copy of the “prospectus.” And that
was all. In reply he received a letter stating that “in consideration
of” his “many dignities and great learning” he had been nominated “an
officer of this academy” and had been awarded “_la médaille de première
classe_” for humanitarian work and scientific merit. In order to obtain
these tokens of the “Academy’s” regard it would be necessary to inform
the “Academy” of acceptance “in conformity with Section 19 and 22 ...”
As the Propaganda Department did not consider the diploma and gilt
medal worth $15 even as exhibit for its museum of fakes, the “Form of
Acceptance” was not filled in and returned “in accordance with Section
19 and 22.”
[Illustration: Photographic reproduction (reduced) of the “Form of
Acceptance” to “membership” in the “Italian Physico-Chemical Academy.”
Filling out this blank and sending it _with $15.00_ to the “Academy”
will bring the gilt medal and “diploma.”]
The leading spirits in the operation of this diploma and medal mill are
D. and G. Bandiera, who, so far as we can learn, are neither physicians
nor pharmacists nor have any scientific standing. The “Academy” has
been referred to at various times[294] by The Journal.--(_From The
Journal A. M. A., Feb. 26, 1916._)
[294] J. A. M. A. 48: 2196 (June 29) 1907; Editorial 57: 1373, Berlin
letter, p. 1380 (Oct. 21) 1911; 58: 1455 (May 11) 1912; 60: 770 (March
8) 1913; 60: 1480 (May 10) 1913; 61: 1737 (Nov. 8) 1913.
WHAT IS LIQUID PETROLATUM?
The use of liquid petrolatum in chronic constipation, which has
recently become the vogue, has naturally been commercialized; as a
result, also naturally, claims of superiority of one brand over another
have been made. Some of these claims may have been well founded; others
certainly are not. Some have claimed superiority for those products
made from Russian oil over those made from American oils. As naphthene
hydrocarbons predominate in Russian crude petroleums, and paraffin
hydrocarbons in many or most American crude petroleums, it was assumed
that the petrolatums derived from these sources differed from one
another in like manner. Both the naphthenes and the paraffins are
chemically inert; but some unexplained therapeutic superiority has been
assumed to reside in the naphthenes. Consequently, it has been urged
that the American liquid petrolatums should not be used internally. So
far these claims and counterclaims have been based on much theory and
little fact. The Journal publishes this week a contribution by Benjamin
T. Brooks, Senior Fellow in charge of petroleum investigations at
Mellon Institute, Pittsburgh. Brooks calls attention to the fact that
Marcusson, in 1913, pointed out that most of the so-called “mineral
oils” used for therapeutic purposes contain no paraffin hydrocarbons
whatever; that they consist solely of naphthenes and polynaphthenes.
Brooks confirms this statement so far as American liquid petrolatums
are concerned. He states that many American petroleums, such as most
of those from the Gulf region, are like the Russian in containing no
paraffin; and that, in the case of those petroleums that do contain
it, the customary refinery method of removing paraffin is sufficient
to produce true naphthene and polynaphthene petrolatums. “The claim
that only Russian oils belong in this class,” he says, “has no basis
in fact and has been advanced presumably for business reasons.” The
name “paraffin oil” applied to these liquid petrolatums, then, is a
misnomer. The new name, “white naphthene oils,” suggested by Brooks,
seems superfluous, however, since the pharmacopeial title, “liquid
petrolatum,” is subject to no such objection.--(_Editorial from The
Journal A. M. A., Jan. 1, 1916._)
THE LOWENTHAL POSTGRADUATE COURSE
Which Tells How to Make Diagnoses Accurately, Scientifically Check
the Christian Scientists and Increase Your Earning Power
During the past year The Journal has received letters from physicians
in various cities asking for information regarding the “Post Graduate
Course of Lectures and Clinics on Nervous and Mental Diseases” which
was going to be given in their respective cities by Dr. Albert A.
Lowenthal of Chicago. The following inquiries are typical:
“_To the Editor._--Please note the enclosed letter from the
American Organotherapy Company which appears to be conducted by
Lowenthal. The proposition of conducting these clinics impresses me
as a piece of colossal gall which is amazing even in these days. Do
you know anything about this matter?”
“_To the Editor._--Who the dickens is Albert A. Lowenthal, M.D.?
Note the circular enclosed. I have blue circled the remarks he
evidently thinks will attract.”
In May, 1919, Chicago physicians received a form letter, signed,
and on the stationery of, Albert A. Lowenthal, notifying them that
Dr. Lowenthal was about to “give a Post Graduate Course of Lectures
and Clinics on nervous and mental diseases” in the “Banquet Hall,
Morrison Hotel.” Enclosed was a “Programme and Reservation Card” and
a self-addressed envelop for physicians to notify Dr. Lowenthal that
they would be present. In addition to showing physicians “how to make
diagnoses accurately,” Dr. Lowenthal offered to “explain fully how to
scientifically check the Christian Scientists and increase your earning
power!” And all for nothing!
At later dates similar letters were received by physicians in other
cities, on the stationery of the “American Organotherapy Company, Room
902, 31 North State St., Chicago.” Dr. Lowenthal, whose Chicago office
is Room 901, 31 North State St., is, apparently, president, treasurer
and practical owner of this company. Enclosed with each of these
letters--which offered the same inducements, free--was an envelop
addressed to Albert A. Lowenthal in care of the hotel at which Dr.
Lowenthal would stay while in that city. There was also a “Programme
and Reservation Card” as in the case of the letters sent to Chicago
physicians.
According to our records, Dr. Albert A. Lowenthal was born in Chicago
in 1874 and was graduated by the College of Physicians and Surgeons,
Chicago, in 1895, receiving his license the same year.
In a leaflet issued some time ago by Albert A. Lowenthal, M.D., “for
the sole purpose of enlightening Prospective Patients in regard to
the therapeutic value of the Organo Therapy Treatment for Nervous
Diseases,” we learn that Dr. Lowenthal is, or was:
“Professor Nervous and Mental Diseases, Chicago Hospital College of
Medicine.”
“Formerly Professor Nervous and Mental Diseases, Dearborn Medical
College, Jenner Medical College.”
“Adjunct Professor on Neurology and Psychiatry, University of
Illinois College of Medicine.”
“Formerly Physician Illinois Eastern Hospital for the Insane.”
“Formerly Supt., Riverview Hospital for Nervous Diseases, Kankakee,
Ill.”
“Formerly on Advisory and Associated Attending Staff Cook County
Hospital.”
In Polk’s Medical Directory for 1904, Dr. Albert A. Lowenthal’s name
appeared, under Chicago, at 910-912 Chicago Opera House Building.
He was described as “Superintendent of Lowenthal’s Sanitarium.” In
the same issue of the directory, there was a display advertisement
of the Lowenthal Sanitarium, which, while located at Kankakee, Ill.,
had its “main offices” at 912 Chicago Opera House Bldg., Chicago. The
advertisement was headed “GOAT LYMPH TREATMENT,” and read in part:
“Goat Lymph has revolutionized medicine, and has been adopted by
the scientific medical world as the only therapeutical agent that
will absolutely bring about positive results in chronic conditions,
such as Neurasthenia, Nervous Collapse, Paralysis, Locomotor
Ataxia, Brain Fag, Oncoming Insanity, Chronic Stomach Disorders, in
fact such diseases needing cell stimulation.”
It mentioned further that Dr. Albert Lowenthal “introduced Goat Lymph
to the medical world as a curative agent.”
A few years ago a Chicago concern, known as the “American Animal
Therapy Co.,” put out such products as “Lymphoid Compound (Lowenthal),”
“Ova Mammoid (Lowenthal),” “Prostoid (Lowenthal),” etc. The American
Animal Therapy Co. had for its manager James M. Rainey. Rainey also
operated the “Rainey Medicine Co.,” a mail-order “patent medicine”
concern that sold “Vitaline,” a “general debility cure.” The Rainey
“Vitaline” quackery was exposed in The Journal, Oct. 1, 1910, and the
matter appears in “Nostrums and Quackery.”
When the American Animal Therapy Company was operating from 84 Adams
St., Chicago, it claimed to have a hospital and laboratory at Kankakee.
At the same time letters were being sent out on the stationery of
“The Lymph Hospital,” signed Albert A. Lowenthal, M.D. Although this
“hospital” was at Kankakee, Ill., the address on the stationery was 84
Adams St., Chicago, and its telephone number was that of the American
Animal Therapy Company. According to the stationery, the “Medical
Department” of the Lymph Hospital was “under the personal direction
of Dr. Albert A. Lowenthal, who introduced the Lymph Compound and
Lymphoid Compound to the Scientific Medical World as a curative agent
in Chronic Nervous conditions.” A layman received a letter from the
“Lymph Hospital” urging him to take “Lymphoid Compound.” Later he
received a “follow-up” letter, from which the following extracts are
made. Capitals used as in the original:
[Illustration: Some letterheads (greatly reduced) of concerns in which
Dr. Albert A. Lowenthal has been interested.]
“Do you know that the doctors of this country are using the
LYMPHOID COMPOUND EXCLUSIVELY in all cases, where the nervous
system is greatly involved, with the most MARVELOUS RESULTS. ISN’T
THAT SUFFICIENT PROOF as to the merit of the remedy?”
“... Nobody can tell you there is something just as good, because
THERE IS NOTHING JUST AS GOOD AS THE LYMPH--in fact IT IS THE ONLY
THING THAT CAN BE DEPENDED UPON.”
“... Our Dr. Lowenthal gives his personal attention to all cases
at the Hospital and devotes a portion of his time advising by
mail those persons under treatment who are unable to come to the
Hospital. He is a man of WORLD WIDE REPUTATION IN TREATING NERVOUS
DISEASES--HIS ADVICE ON CASES LIKE YOURS IS WORTH EVERYTHING TO
YOU.”
“Think this over and if you do, you will write an order today for
the Lymphoid Compound. The home treatment costs $9.50 for thirty
three days--think of that. You have our physician’s advice and care
free of charge--could anybody ofter more to you?”
In 1908 Dr. Lowenthal appeared as a witness for Edward R. Hibbard,
who was being prosecuted by the federal authorities. Hibbard operated
a “men’s specialist” office in Chicago; it had two entrances and a
different name for each entrance--the “Boston Medical Institute” and
the “Bellevue Medical Institute.” Hibbard was found guilty of fraud in
the operation of this concern and was fined $1,500. The transcript of
the testimony in the Hibbard case records that Dr. Albert A. Lowenthal,
when on the stand, claimed to “have treated as many nerve patients as
any nerve specialist in Chicago.” He further declared, according to the
transcript, that physicians who make a specialty of nervous diseases
“mature in about ten years” and that after that time most of them
become nervous wrecks or insane. This was in 1908. In this connection
it is worth noting that in letters sent out by Lowenthal in May, 1919,
he claimed:
“In the past twenty-five years I have limited my work to
neurological and psychological cases....”
In 1908 also, Dr. Lowenthal was sending out letters to Illinois
physicians in his capacity as secretary of the “Physicians’ League of
Illinois.” The “league” issued a “report on candidates for governor
and members of legislature,” giving the names of the various political
candidates for office whom “the members of the league can safely
support.” There were no “membership” fees and a physician who wrote
asking “who foots the bills” received no reply.
In 1915 Albert A. Lowenthal, whose “valuable discoveries in the
domains of Organo Therapy, Neurology and Pediatrics, have given him an
international reputation as a Neurologist, Alienist and Climatological
Expert of high standing,” was “Medical Superintendent” of the “National
Sanitarium Information Bureau.” This purported to represent the
“Leading Sanitariums and Health Resorts in the U. S.” The “Bureau”
expected to make its “profit from the 10 per cent. honorarium received
on every referred patient.” The “Business Manager” of this concern was
one Hubert Miller, M.D. The following advertisement appeared in the
classified department of the _St. Louis Post Dispatch_ in 1915:
[Illustration]
A layman who wrote in answer to this advertisement received a letter
from Dr. Lowenthal in which he said that it was his intention to take
about thirty patients south with him for four months--cost of trip
$500, which includes medical treatment, board, etc. Dr. Lowenthal
stated further:
“I have treated probably more cases of Locomotor Ataxia and
Paralysis than any Physician in United States and can honestly
state that with Organo Therapy Treatment your walk can be improved
and pains controlled.”
In March, 1919, Dr. Lowenthal paid a visit to Spokane, Wash., and
Portland, Ore. A Portland paper heralded his coming and printed a
picture of “Dr. A. A. Lowenthal, World famous alienist.” The paper
described Dr. Lowenthal as “the alienist consulted in the Harry Thaw
case” and the one “who treated John Alexander Dowie of Zion City
fame and Pope Leo XIII.” The fulsome puffery that Dr. Lowenthal got
while in Spokane drew criticism from one or two members of the local
medical profession, who wrote to the newspapers protesting. One of
the physicians who thus wrote declared that Lowenthal’s “coming was
announced in a circular sent through the Owl Drug Company which is
agent for the sale of products of an organo-therapy company.”
Apparently, it was after Dr. Lowenthal’s return from the Pacific Coast
that he commenced to announce his “Post-Graduate Course of Lectures and
Clinics” to the physicians of Chicago, Denver, St. Louis, Columbus,
etc.--and, incidentally, to bring to the attention of the medical world
the alleged virtues of the products of the American Organo-Therapy
Company.--(_From The Journal A. M. A., July 3, 1920._)
MEDICAL SOCIETY OF THE UNITED STATES
From “Division of Fees” to “Down with Autocracy”
The “Medical Society of the United States” has for its “Honorary
President” one A. H. Ohmann-Dumesnil, A.M., M.D., M.E., Sc.D., Ph.D.,
and for its “Secretary and Treasurer” one Emory Lanphear, M.D., C.M.,
Ph.D., LL.D. As originally planned, the “society” seems to have been
based on the idea of organizing the “fee-splitters.” In May, 1916,
the birth of the organization was announced to the medical profession
through a letter signed Emory Lanphear, written on the stationery of
the “Medical Society of the United States.” Even in its embryonic
state the society had A. H. Ohmann-Dumesnil, A.M., M.D., M.E., for its
president, and Emory Lanphear, M.D., Ph.D., LL.D., as its treasurer.
The letter read in part:
“We--the majority of the medical profession--who believe in
division of fees (_i. e._, that the surgeon should not ‘hog’
the whole of a patient’s money and leave nothing for the family
doctor), are no longer welcome in the A. M. A. We are therefore
organizing the Medical Society of the United States, which will not
be conducted for the benefit of a few selfish egotists. We would
like to have you with us.
“It costs only $1.00 to join. This covers dues for 1916, and
includes expense for the beautiful certificate of membership
(suitable for framing), which you will receive on admission. Fill
enclosed blank and return to me with $1.00.”
But presumably the idea of organizing on a basis of “fee splitting”
did not make a hit, so the lure was changed. Today physicians are
approached with the plea that the “Medical Society of the United
States” will make the medical world free for democracy; it is, we are
assured, a “Society of Protest Against the Autocracy of the A. M. A.,”
and a “Society of Medical Democracy.”
Membership costs “only $1.00 ... including the cost of a beautiful
certificate of membership.” No penalties or punishments are involved
for belonging to other societies, and:
“Joining our body need not affect your membership in any other
society--even the A. M. A., if you wish to belong to it, and be
‘bossed’ by the ‘Simmons Gang’.”
The dollar for the “beautiful certificate” and membership is solicited
by means of circular letters signed “Emory Lanphear,” coming from 3447
Pine St., St. Louis, Mo., the address of what has been variously
called the “American Polyclinic,” the “American Hospital,” and later,
the “German Hospital.” The “Surgeon-in-Charge” of the “German Hospital”
is Emory Lanphear, M.D., C.M., Ph.D., LL.D. When running under the
name of the “American Hospital,” Lanphear solicited operative work on
a “division of fees” basis, which, the general practitioner was told,
meant that “you are to have 40 per cent. of all fees received from your
patients sent to our staff for operation or treatment.”
With the change in name from “American Hospital,” to “German Hospital,”
Lanphear appealed for a “portion of your operative work on a basis of
pure reciprocity.” This “pure reciprocity” seems to have been a still
more liberal distribution of the patient’s money, for from a 40 per
cent. basis it was raised to an even fifty-fifty. Said Lanphear, in a
letter sent out a few months ago:
[Illustration: The “Medical Society of the United States,” was
originally organized on a basis of “fee-splitting,” as is shown by the
reduced facsimile of a letter sent broadcast in 1916, announcing the
birth of the new “society.” Apparently, “fee-splitting” as a rallying
point did not bring in the desired returns, so today the “Medical
Society of the United States” is alleged to be a “Society of Protest
Against the Autocracy of the A. M. A.”]
“I wish also to inform you in spite of the despicable opposition
of the hypocritical gang in charge of the A. M. A., and the no
less contemptible action of the St. Louis Medical Society, I am
going to remain in St. Louis and continue to do surgical work upon
a ‘division of fee’ basis. To be more explicit, if you bring me a
case for operation I shall allow you one half of the fee for your
time, trouble, responsibility and help in the management of the
case.”
Before leaving the interesting professional personality of Lanphear,
and carefully avoiding any details of a personal nature, we may remind
our readers that as long ago as 1908 Lanphear was the “Dean” of the
“Hippocratean College of Medicine,” with A. H. Ohmann-Dumesnil, A.M.,
M.D., M.E., Sc.D., “Vice-Dean.” At that time Lanphear sent out letters
to physicians proposing the organization of a “Post Graduate Faculty”
on the following basis:
“Those who hold full professorships shall purchase stock in the
corporation to the amount of $1,000.00; those who become lecturers
or instructors shall pay in the sum of $500.00; those who are to be
merely clinical assistants will buy ten shares of stock, $100.00.”
The “Hippocratean College” was a “sundown” affair; it never graduated a
student, and expired in 1910.
[Illustration: Reduced facsimile of the letter-heads of an institution
known variously as the “American Hospital” and the “German Hospital.”
The change in name from “American” to “German” seems to have taken
place early in 1915--when things German were more popular and
profitable than they are today!]
But to come back to the “Society of Medical Democracy”: The “Medical
Society of the United States” seems to have been born in 1916. Its
parents, so far as is apparent, seem to have been Lanphear and
Ohmann-Dumesnil. The latter, it may be remembered, used to be the
editor and proprietor of the _St. Louis Medical and Surgical Journal_,
a publication so obviously venal, that its value to the nostrum makers,
whose interests it espoused, must have been small. Advertising pages,
“original articles” and “editorials”--all were used to puff nostrums of
the crudest type. It was Ohmann-Dumesnil and his journal that came to
the defense of the “patent medicine” interests when they were so hard
hit by Mr. Adam’s “Great American Fraud” series. In commenting on this
phase of “patent medicine” activities, _Collier’s_, in January, 1907,
said:
“Headache powders came in for a considerable share of attention in
the patent medicine articles. There was much talk of libels among
the headache powder makers, but they decided upon the safer methods
of hiring a meretricious medical publication, the _St. Louis
Medical and Surgical Journal_, to print an article in which the
_Collier’s_ statements were branded as lies, and the _Collier’s_
editors and writers as liars and libelers. This article the
Proprietary Association of America circulated in pamphlet form. The
journal which printed it died a natural death a few weeks later.
Its editor, one A. H. Ohmann-Dumesnil, has just appeared in the
public prints in an unsavory connection with a corrupt lobbying
project in St. Louis.”
Some of the nostrums that Ohmann-Dumesnil has recommended are:
“Sanmetto,” “Gonosan,” “Cactina Pillets,” “Pepto-Mangan,” “Satyria,”
“Campho-Phenique,” “Tongaline,” “Germiletum,” “Narkogen,” “Nosophen,”
“Mercauro,” “Arsenauro,” and “Hydrozone.” Many of these testimonials
were, of course, used by the manufacturers in their advertising
“literature.”
At the time that the Medical Society of the United States was being
organized--in 1916--there was published what purported to be a
preliminary program of its first meeting. The meeting was held in St.
Louis, and the program, while containing the names of men with special
fads or interests to exploit, also contained the names of some men of
standing. It appeared, however, on investigation, that at least some
of the latter had but a hazy conception of the use to which their
names were being put, and protested vigorously on learning the facts,
repudiating the organization.
[Illustration: Reduced facsimile of a letter sent out in 1912,
soliciting the purchasing of stock in the “American Hospital” on a
division of fee basis--forty-sixty!]
Now, in 1918, another drive is on for membership; letters signed “Emory
Lanphear” are being sent to various selected groups of physicians. For
example, the Eclectics are being coaxed by a letter which commences:
“We want every reputable Eclectic practitioner in this country to
join our society of protest against the iniquities of the A. M. A.”
An identical letter has been addressed to Homeopaths, the words
“Homeopathic practitioner” being substituted for “Eclectic
practitioners.” In all of the letters the “beautiful certificate
of membership” is emphasized, and the trivial cost--“only $1.00 a
year”--is referred to, while the plea: “surely you are willing to help
to that amount to ‘down’ the ‘gang’ in charge of the A. M. A.,” is
featured. Another group of letters has gone out to the graduates of the
Barnes Medical College. This commences:
“Most graduates of ‘Old Barnes’ have joined our society of protest
against the iniquities of the A. M. A. Why should you also not come
in? It costs only $1.00 to become a member, including the cost of a
beautiful certificate of membership.”
Still another group appeal is based on sex; thus Lanphear:
“We want every reputable ‘lady physician’ in this country to join
our society of protest against the iniquities of the A. M. A.”
And yet another:
“You formerly belonged to the Tri-State Medical Society, of which I
was Treasurer for 20 years. It is now dead. I wish you would join
our new society which has superseded Tri-State in this territory.”
With these various letters is enclosed a “preliminary program” of the
1918 meeting which is to be held October 8 and 9 in Chicago. As might
be expected, many of the names on the program are characteristic of the
organization and an interesting “story” might be made from the material
in The Journal’s files on the individuals. Such names are of men, who,
professionally speaking, range from faddists, who ride grotesque and
bizarre medical hobbies, to those who with special interests to exploit
and unable to use reputable medical organizations for that purpose,
take refuge in such hybrid conglomerations as the Medical Society of
the United States. Not that the program contains the names of crude
quacks, or obvious medical swindlers. It is representative, rather, of
that twilight zone of professionalism, the penumbra, in whose uncertain
light it is difficult to distinguish between the unbalanced visionary,
with a fad, and the more sinister near-quack, with a “scheme.”--(_From
The Journal A. M. A., Oct. 5, 1918._)
THE NATIONAL FORMULARY--A REVIEW OF THE FOURTH EDITION
The fourth edition of the National Formulary appears simultaneously
with the U. S. Pharmacopeia IX, and is to become official at the same
time (September 1). The principles which determine its scope, as
frankly set forth in the preface, are apparently the same as those
applied, though more faint-heartedly, in the compilation of the
Pharmacopeia. A statement in the preface of the new National Formulary
runs:
“The scope of the present National Formulary is the same as in
previous issues, and is based on medical usage rather than on
therapeutic ideals. The committee consists entirely of pharmacists,
or of men with a pharmaceutical training, and it cannot presume
either to judge therapeutic practice or to follow any particular
school of therapeutic practice. The question of the addition or
deletion of any formula was judged on the basis of its use by
physicians and its pharmaceutical soundness. The considerable use
by physicians of any preparation was considered sufficient warrant
for the inclusion of its formula in the book, and a negligible or
diminishing use as justifying its exclusion.”
Part I of the volume contains formulas, good, bad and indifferent,
including the equivalents of a large number of shotgun proprietaries.
Part II contains descriptions of drugs. This is a new feature. The
purpose is to provide standards for those drugs not described in
the Pharmacopeia but used in N. F. preparations. Many of these drugs
were described in the U. S. Pharmacopeia VIII, but have not been
included in the ninth revision. Practically all are either worthless
or superfluous. Part III contains descriptions of special tests and
reagents.
Among the therapeutically useful formulas are those for aromatic castor
oil, emulsion of castor oil, sprays or nebulae, solution of aluminum
acetate, solution of aluminum subacetate and wine of antimony. The two
last named are also included in “Useful Drugs.” Several formulas for
new classes of preparations which may or may not be found superior
to old forms are paste pencils for the application of medicaments to
limited areas of the skin, mulls, which are ointments spread like
plasters, and fluidglycerates, which are fluidextracts in which
glycerin takes the place of alcohol. It should be noted also that, as a
result of criticism, the alcohol content of some preparations has been
reduced.
As a whole, the present edition of the National Formulary, like its
predecessors, is “pharmaceutically useful but not a therapeutic
necessity.” To say that it is not a therapeutic necessity is to
state the matter mildly, since most of the formulas and almost all
of the drugs described have been discarded long since by rational
therapeutists. So long as there are physicians who prescribe
therapeutic monstrosities, however, the druggist should have the
aid that is furnished by this book in compounding them. From the
pharmacist’s point of view, therefore, the book is a valuable one.
Physicians who have a scientific training in the pharmacology of drugs
will not want it; others will be better off without the temptations
offered by its many irrational formulas.--(_Book Review in The Journal
A. M. A., Sept. 2, 1916._)
NONSPECIFIC PROTEIN THERAPY
The treatment by nonspecific methods in a series of cases of influenzal
pneumonia has been the subject of two recent papers.[295] These methods
are a development of the work of Ichikawa, Kraus, Lüdke, Jobling and
Petersen, and others on the treatment of typhoid fever and of Miller
and Lusk’s work on arthritis. In the original work in this field it
was recognized that there were certain inherent dangers in the method
and that wide application would be permissible only with the greatest
caution and under careful control.
[295] Roberts, Dudley, and Cary, E. G.: Bacterial Protein Injections
in Influenzal Pneumonia, J. A. M. A. =72=:922 (March 29) 1919. Cowie,
D. M., and Beaven, P. W.: Nonspecific Protein Therapy in Influenzal
Pneumonia, J. A. M. A. =72=:1117 (April 19) 1919.
When vaccines and other toxic protein substances are injected
intravenously a train of reactions takes place that includes: (_a_)
a primary leukopenia, followed by a leukocytosis; (_b_) a primary
lessening of the coagulability of the blood, followed after some
interval by a reduction of the coagulation time; (_c_) a pronounced
lymphagogue effect, the flow of lymph from the thoracic duct being
increased threefold; (_d_) a hyperperistalsis of the intestinal tract,
and (_e_) a marked splanchnic engorgement with a resulting lowering of
the systemic blood pressure. The alteration of the coagulability of the
blood, together with the vascular engorgement of the splanchnic area
and the coincident increase in motility of the intestinal tract that
follow the therapeutic injection, all tend to increase the possibility
of intestinal hemorrhage. Protein therapy is therefore not a safe
procedure in this particular disease. That we are able to terminate a
certain number of cases of typhoid fever by crisis by means of such
injections is of very great interest from a theoretical point of view.
In the treatment of arthritis, the results seem much more satisfactory.
The work of Miller and Lusk[296] has been confirmed by a number of
observers, among them Culver, Cecil, Snyder, Cowie and Calhoun; and
there seems little doubt that we may be able to give prompt relief and
even permanent freedom from symptoms in a considerable percentage of
cases of acute and subacute arthritis, especially those classed as of
rheumatic origin--and this with practically no risk to the patient.
[296] Miller, J. L., and Lusk, F. B.: The Treatment of Arthritis by the
Intravenous Injection of Foreign Protein, J. A. M. A. 66: 1756 (June 3)
1916; The Use of Foreign Protein in the Treatment of Arthritis, ibid.
67: 2010 (Dec. 30) 1916.
As with other new therapeutic measures, there is still some uncertainty
as to the proper dosage, which is a matter of considerable importance,
in order to arrive at a just estimate of the relative advantage or
danger in the treatment. Typhoid vaccines have been extensively used
because they are readily procured and give a prompt and sharp reaction.
However, they have the disadvantage of inexactitude in the bacterial
count, as well as being of varying degrees of toxicity, the latter
factor depending not only on the use of different strains of bacteria
in their preparation but on the age of the vaccine. Synder,[297]
as well as other workers, is of the opinion that the primary dose
should be small--from five to ten million organisms--and that the
dose of typhoid bacilli injected should never exceed two hundred and
fifty million. While a sharp reaction on the part of the patient
is apparently a desideratum, a sufficient response can usually be
elicited with a relatively small dose. There is no object in subjecting
the patient to the risk of the profound depression that follows
occasionally in the wake of large doses. Indeed, the only serious
results so far ascribed as due to this form of therapy have followed
very large doses or the use of relatively large doses in moribund
patients; or such unreasonable procedures as the intravenous injection
of milk. It is true that milk injections were recommended by some of
the German investigators, but they were always used intramuscularly.
[297] Snyder, R. G.: A Clinical Report of Nonspecific Protein Therapy
in the Treatment of Arthritis, Arch. Int. Med. 22: 224 (Aug.) 1918.
In the treatment of pneumonia, Roberts and Cary[4] have employed a
vaccine made up of 100 million of each of the following organisms per
cubic centimeter: influenza bacilli, pneumococci, staphylococci and
streptococci. Of this vaccine they injected, intravenously, first
0.5 c.c., later 1 c.c. In the series of 200 patients so treated there
was no evidence of injury to the patients in any way. The mortality in
this series was 9.5 per cent.; in a series of eighty-six patients not
treated with vaccine, the mortality was 31.2 per cent. In the untreated
series, 20 per cent. recovered by crisis; in the treated, 36 per cent.
so recovered. Before any reliance is placed on such statistics they
should be analyzed and compared carefully according to age periods, as
the death rate may vary at different ages. Cowie and Beaven[298] used
typhoid vaccine in the treatment of their patients, and they consider
the vaccine shock as indicated only in the early stages of pneumonia.
[298] Report of International Health Board, Social Medicine, Medical
Economics and Miscellany, J. A. M. A. 72: 751 (March 8) 1919.
Before applying the treatment to such diseases as pneumonia it would
seem that prudence would demand a thorough familiarity with the range
of the reaction and the degree of toxicity of the preparation it is
intended to use by first employing it in some arthritic cases. In
pneumonia we must ever keep before us the vital factor of cardiac
impairment; and certainly we must not undertake any measure that may
depress the function of the heart. In arthritis this danger is largely
a negligible one; and, with proper precaution, nonspecific therapy is
not only without risk but indeed frequently followed by gratifying
clinical improvement. Only in the light of experience gained in the
manner indicated would it seem permissible for us to attempt to extend
this form of therapy to more acute infections.--(_Editorial from The
Journal A. M. A., May 17, 1919_.)
WILLARD EALON OGDEN
A “Specialist in Proctology” and His “Clinics”
Within the past few weeks a number of inquiries have reached _The
Journal_ from physicians in Ohio, Indiana and Pennsylvania. Those that
follow are typical:
“I am in receipt of literature from H. L. Roberts, 1126 Masonic
Temple, Chicago, advertising clinic in Cleveland by Dr. Willard E.
Ogden who claims to be a member of the Chicago Medical Society and
the A. M. A. What can you say of this man and his methods?”
“I am enclosing a folder received a short time ago. I would be glad
to know if Dr. Ogden is a member of the A. M. A. as he claims to
be.”
“The enclosed folder has been sent to many doctors in Indiana. The
purpose is plain. The attached post card on this one was returned
to him for further literature.”
[Illustration: Photographic reproduction of one of Ogden advertisements
in Chicago newspapers at the time he was at 36 W. Randolph Street.]
In each case the correspondents send in a four-page folder bearing the
title “Proctology, A Clinic. Who? Where? Why?” Three of the four pages
purport to answer the interrogations given on the title page. Under
“Who?” we read:
DR. WILLARD E. OGDEN
Chicago, Ill.
SPECIALIST IN PROCTOLOGY
_Member Chicago Medical Society and A. M. A._
_Author of “Improved Method of Treating Rectal Diseases”
Formerly associated with Drs. Burleson & Burleson
Grand Rapids, Mich._
Under the question “Where?” there appears the statement that “Dr.
Ogden Will Hold a Clinic for The Treatment of Rectal Diseases” and the
name of the city and the dates of the “clinic” are inserted with a
typewriter.
Under “Why?” we read:
“Dr. Ogden does not use the usual surgical methods. His many years
of experience in the treatment of Rectal Diseases (during which
time he has been associated with the leading Proctologists of
America) have enabled him to develop a system of office treatment
_which is not taught by any other practitioner_.
“Tear off, sign and mail attached postcard and I will send you a
booklet giving you full particulars as to the course.
Yours truly,
H. L. Roberts, Business Manager.
“Eighty-three per cent. of the people have some Rectal trouble.
THIS IS THE DAY OF SPECIALISTS. Why not fit yourself to specialize
in Proctology?”
The fourth page is a post card addressed to “H. L. Roberts, Room 1126,
Masonic Temple, Chicago.” On the reverse side there is a printed
statement which the recipient is expected to sign to the effect that
he is interested in “Dr. Ogden’s Clinic” and wishes to have “full
particulars of the course.”
A visit to Room 1126, Masonic Temple, failed to disclose the name of
H. L. Roberts, either on the door (or doors, for there are two rooms
having this number) or on the office building directory board. In fact,
Rooms 1126 seem to contain a somewhat miscellaneous assortment. The
signs, either on the door or on the directory board, show that there
is a public stenographer (who operates a “Mailing Service,” and does
“Addressing, Mailing, Multigraphing, Mimeographing”), a bookstore, a
chocolate company, a publishing company, a lumber company, and one or
two other concerns; but the name of “H. L. Roberts” does not appear.
Incidentally, no “H. L. Roberts” is to be found listed in the Chicago
telephone directory.
A few yards away from Rooms 1126 and on the same floor there appears
the name, “Dr. Willard E. Ogden” on Room 1102.
According to our records, Willard Ealon Ogden was born in 1866. Before
taking up the study of medicine he seems to have been a preacher. In
1899 he was graduated by the Saginaw Valley Medical College, Saginaw,
Mich. He was licensed in Michigan in 1900, in Illinois and Indiana in
1913, and in Wisconsin in 1921. From 1900 until 1904 he practiced in
Lyons, Mich.; from 1906 until 1911 he was at Ionia, Mich.
In 1911, he was in Grand Rapids, Mich., and was associated with
Burleson and Burleson, an advertising pile cure concern. From some
of the voluminous Burleson advertising on file, we learn that they
“cure all diseases of the rectum (except cancer);” and claim to have
“the most successful method ever discovered,” and to have cured “many
desperate cases that have been given up to die.” Furthermore, they
“guarantee to cure in every case or make no charge.”
On Jan. 1, 1914, Ogden was sending out a card to physicians in which
he stated that he had removed from Grand Rapids, Mich., and LaPorte,
Ind., to 36 W. Randolph St., Chicago, and that he would limit himself
“exclusively to the treatment of diseases of the rectum.” Later, Ogden
was sending out an advertising booklet filled with testimonials.
In 1914, Ogden was carrying display advertisements in Chicago papers
reading, in part, in large back-faced type: “Piles Cured Absolutely
Without Knife, Anesthetics, Pain or Loss of Time.... Cure Guaranteed or
Money Refunded.”
In March, 1918, he became a member of the Chicago Medical Society and
qualified for Fellowship in the American Medical Association, August,
1918.
In 1921, Ogden had a copyrighted mail-order course on the “Treatment
of Rectal Diseases by Improved Method.” This “course” consisted of
thirty-eight pages of foolscap printed on one side in imitation
typewriting. The material abounded in typographical errors. Among
the proprietary products recommended in this “course” as “essential”
to those taking it, was “Mecca Ointment.” This nostrum, made by a
Chicago concern, was declared misbranded in 1916 because of false
and fraudulent claims made knowingly, recklessly and wantonly. The
“course” was divided into ten parts, and with it, apparently, came
ten consecutively numbered sealed envelops, and the purchaser was
instructed to open these envelops, one at a time, as he completed the
corresponding part in the “course.” He would there find questions which
were to be answered and returned to Ogden. This, according to the
description, was to enable Ogden to determine whether it was necessary
to “enter more into detail upon that particular subject,” which, he
stated, he would gladly do if necessary.
[Illustration: Photographic reproduction (reduced) of the first page of
a booklet Ogden was sending out in the latter part of 1914.]
Furthermore, the purchaser had the privilege of asking questions of
Ogden relative to symptoms, diagnosis and treatment for a period of
six months after the purchase of the “course.” Although, in Ogden’s
opinion, “you should have the subject well understood long before that
time.”
The charge for this course and “services as outlined” was $200, but in
order to show his confidence in the ability of those who purchased it,
Ogden was willing to take $100 down and the other $100 paid in “five
per cent. of monies received from CURED patients” until the balance was
paid.
Reverting to the present “post-graduate course” and “clinic”: Those
who send in the postal card to “H. L. Roberts” receive a form-letter,
signed “H. L. Roberts” in facsimile handwriting, stating that
information was enclosed “regarding THE OGDEN METHODS” and stating
that Dr. Ogden would be in Indianapolis or Cleveland or Pittsburgh, as
the case might be, on a certain date and that the fee for the “clinic”
would be $100. With this letter is an eight-page pamphlet entitled
“Some Facts Concerning the Ogden Method of Treating Rectal Diseases.”
The first page is headed in black-faced type: “About References
and Endorsements.” It then states that the “usual references and
endorsements are omitted from this booklet.” Further:
“As to Dr. Willard E. Ogden: The professional and social standing
of Dr. Ogden is such that he does not need to offer any.
“As to ‘THE OGDEN METHOD’ and its value to you in your professional
work: What others say or think has little if any weight. You are
your own man. You do your own thinking. You decide for yourself--Do
you not?”
[Illustration: Photographic reproduction (greatly reduced) of an
advertisement of the Burleson concern with which Ogden was connected
previous to 1914, and which connection he is capitalizing in his
present advertising.]
The booklet gives an outline of the “Course of Instruction,” which is
almost identical, word for word, with the outline given in the letter
advertising the mail-order course previously referred to.
The booklet further states that “THE OGDEN METHOD has entirely
eliminated the use of cautery, the ligature or any injections, in the
treatment of hemorrhoids,” but that “the use of the electric current
has proved to be the very correct method in such cases, as will be
demonstrated at the clinic.” The booklet reiterates the statement that
Ogden’s association with the Burleson and Burleson concern at Grand
Rapids makes him “eminently well qualified to instruct members of the
medical profession in this important branch of the medical science!”
In addition to this booklet there is a four-page advertising
leaflet illustrating and describing the “Ogden Rectal Cabinet” and
also the “Ogden Rectal Table and Stool.” There is also a little
postcard--addressed, of course, to “H. L. Roberts”--for the physician
to fill in stating that “you may enroll me as intending to attend Dr.
Ogden’s Clinic in Proctology, to be held at----.” Should the recipient
not fill in and mail this enrolment card he gets another form letter
calling attention to the fact that the enrolment card has not been
received and stating further that “available hotel facilities make it
necessary to limit our enrolment to twenty students.”
Careful search fails to disclose that Dr. Willard Ealon Ogden has ever
distinguished himself in the practice of the specialty in which he now
wishes to instruct physicians. Equally careful search fails to show
that Dr. Ogden has ever published a paper either on any proctologic
subjects or on any other phase of medicine or surgery. Neither does
there seem to be any evidence for the claim that Dr. Ogden “has been
associated with the leading Proctologists of America.”--(_From The
Journal A. M. A., Feb. 4, 1922._)
“PATENTS”
Patent Laws and Patent Office Practice
The inequity of our patent laws, or possibly it would be more correct
to say, of the interpretation of our patent laws, has been commented on
many times in The Journal. The Journal also has had occasion to call
attention to patents that have been issued for obviously unscientific
and quackish devices and preparations. The cases of the preposterous
gas-pipe fake “Oxydonor” and the creatinin mixture for the alleged
conferring of immunity against diphtheria, pneumonia, scarlet fever,
syphilis, tuberculosis, etc., are cases in point.
In a patent issued the early part of this year for the “discovery” of
a method of flavoring Epsom salt, the patent office has, in fatuity,
piled Pelion on Ossa. The “inventor” declares that his invention
relates to a pharmaceutical preparation and a special method of
treatment of the medicinal agents whereby said agent will be rendered
much more efficient in character. He further avows that the “prime
object” of his “invention” is to “disguise the normal taste and impart
an agreeable odor or smell to salts commonly employed as a cathartic.”
Parenthetically it may be said that probably not a day passes that
some physician in the United States does not do substantially the same
thing when writing a prescription. The “inventor” further claims that
the object of his “invention” is to utilize the salts as a vehicle
to carry an antiseptic and anesthetic agent whereby the salts when
administered as a cathartic “will also act beneficially on the entire
digestive tract” and “whereby cramped and spasmodic conditions are at
once relieved with a resulting cure of flatulency, indigestion, sick
and sour stomach, colic and the destruction of worms, etc.”
Such claims are so absurd that the only excuse for commenting on
them is the effect they have on the public mind. The layman reading
the specifications of this patent would naturally conclude that an
invention of great importance had been made--of such importance as to
warrant the government in rewarding its inventor by granting him a
seventeen-year monopoly on the sale of his invention.
The law requires that, to be patentable, inventions shall be new and
useful and shall show a higher degree of skill in their inception than
is naturally to be expected from those who are skilled in the arts to
which the inventions belong. It has been decided again and again that
physicians’ prescriptions are not patentable because it is assumed
that an educated physician will utilize his knowledge of pharmacy in
devising proper compounds of medicines to meet the indications of
disease. When a physician prescribes a dose of Epsom salt to be taken
in one of the official aromatic waters, he does not produce or create a
new invention by so doing. Of course, in one sense every prescription
is an invention--an invention to meet the conditions presented by the
patient--but such inventions are not patentable, because they represent
the ordinary skill of a physician in carrying on his vocation.
If the patent office goes on granting patents for such “inventions” as
flavored Epsom salt, and it should be found financially profitable to
secure such patents and place the products on the market, it will only
be a matter of time before the materia medica will be so restricted
that a physician will be unable to write a prescription without
infringing on somebody’s patent.
The splendid conception of the framers of our constitution in providing
a plan for promoting progress in science and useful arts by granting
to inventors for a limited time the exclusive use of their inventions,
in exchange for the publication of full knowledge thereof, is being
debased. No branch of our government is of greater importance to the
progress of the country than the patent office, provided that office is
intelligently administered. When the patent office is used, however,
for an extention of the nostrum business, founded on the abuse of
patent and trade-mark laws, it becomes a menace to the public health.
The objects of the patent law are being defeated by the practices of
the patent office.--(_Editorial from The Journal A. M. A., June 23,
1917._)
Our Archaic Patent Laws
In this issue we publish two reports of the Council on Pharmacy and
Chemistry which illustrate the weaknesses of the present working of the
United States patent laws. In the first report the Council presents
an investigation of a recently granted patent, and shows that the
patent was issued on the mere claims of the applicant and without the
presentation of any evidence for such claims. The second report--“Need
for Patent Law Revision”--is an appeal to the Patent Office for a
more enlightened administration of the patent law, and it presents a
few illustrations of the unfair protection which has been granted by
the Patent Office. The protest of the Council appears at an opportune
time. In _Science_[299] _the “Patent Office Society,”_ an association
of employees of the U. S. Patent Office, announces that a committee
has been created on request of the National Research Council to make
a study of the U. S. Patent Office and its service to science and
arts. It states that this committee will meet in Washington shortly
to consider the adequacy of the present Patent Office equipment and
the simplification of procedure as well as responsiveness to present
national and international requirements. The committee also hopes
to coordinate, in the interest of an improved public service, the
endeavors of the various national societies, manufacturing interests,
patent bar associations and all others aiming at genuine patent reform.
Unquestionably, there is a growing conviction that in the case of
medicines the monopoly given by the patent laws, if granted at all,
should be granted with greater consideration of the public welfare.
Too often the United States Patent Law has been used to obtain an
unfair monopoly on a medicament or to abet quackery. There is no
question that one of two things is needed: either a radical change
in the patent law itself or the application of more brains in its
administration.--(_Editorial from The Journal A. M. A., Jan. 12, 1918._)
[299] Dec. 28, 1917, p. 629.
Patents Perpetuated by Trade Names
The patent on aspirin[300] (acetylsalicylic acid), controlled by
the Bayer Company, American representative of the Farbenfabriken of
Elberfeld Company, will expire next year (1917). The Journal has
previously stated that the grant of this patent was regrettable and
worked injustice to American citizens. It is unnecessary again to go
into the grounds for this statement; neither in the Farbenfabriken’s
home country, Germany, nor in any other country except in the United
States, has a patent been granted for this product. Owing to their
monopoly, the manufacturers have been able to exact a much higher
price for acetylsalicylic acid, or aspirin, in this country, than
elsewhere. Naturally, the Bayer Company, the American agents, view with
disfavor the prospect of being compelled to share this rich field with
competitors. The foregoing furnishes the answer to inquiries which have
reached us from all over the country with regard to the campaign of
publicity which the Bayer Company has inaugurated in the lay press. A
presumably authentic and apparently candid exposition of the methods
used and the motives behind the aspirin advertising is furnished in
_Printers’ Ink_:[301]
[300] Granted Feb. 27, 1900.
[301] Printers’ Ink, June 29, 1916, p. 189; July 13, 1916, p. 100.
“The manufacturers of aspirin are about to launch an extensive
advertising campaign to clinch the market as far as possible before
the expiration of their patent rights next year.... The purpose
of the campaign is to identify the product with the trademark of
the Bayer Company and to this extent hamper competition after the
expiration of the patent.”
The business of the Bayer Company, the article goes on to say, has been
hurt by the sale of worthless or even harmful imitations put on the
market by irresponsible and unauthorized persons when the present war
stopped importations from Germany.
“The public knew aspirin, but did not know who made it [italics
ours].... When the Bayer Company, Inc., took over the manufacture
of aspirin in this country, the first steps were taken to identify
the product with the firm who made it.... Of course, there are good
reasons why the makers were loth to advertise the product or to
exploit their trademark. As every one knows, the advertising of a
medical proposition is an extremely ticklish subject.... It is easy
to make a misstep. Aspirin is one of those proprietary drugs that
are extensively prescribed by physicians. If anything were done
that might possibly associate this drug with the patent medicines
that are in disfavor with the profession, the valuable influence
and cooperation of thousands of doctors might be lost. It is
believed that this knotty phase of the question is being answered
in the present advertising.... Since nothing is mentioned about
‘medicine,’ ‘cures’ or ‘ailments,’ it is anticipated that there
will be but little objection to the copy. All that the advertising
attempts to do is to link up the name ‘Bayer’ with aspirin....
The nearest the copy gets to medical talk is in this sentence in
very small type at the bottom of the advertisement, ‘The trademark
“Aspirin” (Reg. U. S. Patent Office) is a guarantee that the
monoacetic acid ester of salicylic acid in these tablets is of the
reliable Bayer manufacture.’”
From this it appears that, not content with seventeen years of
monopoly, the aspirin people are attempting to retain a hold on
the market _in perpetuo_ by associating the name of the company
with the trade name “aspirin.” There can be no better time than the
present, therefore, for the medical profession to substitute, for
the nondescriptive name “aspirin,” the descriptive and correct name
acetylsalicylic acid.--(_Editorial from The Journal A. M. A., Aug. 12,
1916._)
Patenting Therapeutic Agents
In the past, therapeutic agents and apparatus have been controlled
by patents and trademarks for profit. If there have been exceptions,
they have been rare. The Principles of Medical Ethics of the American
Medical Association contain this statement: “It is unprofessional
to receive remuneration from patents for surgical instruments or
medicines.” This does not mean that the patenting is wrong in itself;
there are occasions when it is wise, if not necessary, to obtain a
patent in the interest of the public, and, in the case of surgical
instruments and medicines, of the medical profession. In certain
instances it is absolutely necessary that the article produced shall
maintain a definite standard of quality and purity--and, it may be
added, shall be sold at a reasonable price. Enterprising pharmaceutical
manufacturers have usually been ready to appropriate the results of
scientific research by investigators or therapeutic measures suggested
by practicing physicians. Not infrequently, in such instances, the
desire for financial gain has caused the marketing of such products
with extravagant, if not false, claims as to their value. Yet the
patent laws may be used so as to protect and benefit the public and the
medical profession. In research laboratories, work is being carried on
resulting in the production of new therapeutic agents. It is important
that these agents shall be so controlled that they may be made
available without subordination to commercial interests. It has become
practically necessary, therefore, for research workers to protect
their products in the interest of the public welfare and scientific
medicine. It has not been an easy matter to decide how best to bring
about the desired results. This question has been before the Board of
Trustees of the American Medical Association; and, in 1914, the House
of Delegates passed a resolution authorizing the board to accept at its
discretion patents for medical and surgical instruments and appliances;
as trustees, for the benefit of the profession and the public,
provided that neither the Association nor the patentee should receive
remuneration from these patents. The Rockefeller Institute for Medical
Research has solved the problem in a similar manner. In connection with
the report of the discovery of several new arsenic compounds, Jacobs
and Heidelberger,[302] working in the Rockefeller Institute, say:
[302] Jacobs, W. A., and Heidelberger, M.: Aromatic Arsenic Compounds,
II, The Amides and Alkyl Amides of _N_--Arylglycine Arsonic Acids, J.
Am. Chem. Soc. =41=:1587 (Oct.) 1919.
It may be appropriate to mention here that this substance and
related compounds, described in the present and following papers of
the series, are covered by U. S. Patents Nos. 1280119-27. Patents
have also been applied for in foreign countries. All discoveries
made at the Rockefeller Institute are made freely available to
the public, in accordance with the philanthropic purposes of the
institution. In order to insure purity of product and protection
against exploitation, it has been deemed necessary in certain
instances to protect the discoveries by patents. It is the purpose
of the institute to permit any drugs which may prove of practical
therapeutic value to be manufactured under license by suitable
chemical firms and under conditions of production which will
insure the biological qualities of the drugs and their marketing
at reasonable prices. Other than through the issuance of license,
the Rockefeller Institute does not participate in any way in the
commercial preparation or sale of the manufactured chemicals; and it
receives no royalties or other pecuniary benefits from the licenses
it issues.
Here we have medicine at its best. The altruism of pure science
operating for the benefit of the general public: scientific
therapeutics freed from commercial domination.--(_Editorial from The
Journal A. M. A., Oct. 18, 1919._)
PHARMACEUTICAL BARNUMS
Does the public love to be humbugged? We doubt it. That we, whether
sage or fool, _are_ humbugged is undeniable. We are humbugged just
to the extent that we are ignorant. There lies one of the most
powerful factors operating to the advantage of the “patent medicine”
maker and the quack. The layman’s ignorance of the possibilities and
limitations of drugs is wide and deep. Hence the ease with which he
is fooled on this subject. A seeming frankness in advertising being
the order of the day, the nostrum maker makes a pretense of telling
what is in his stuff without disclosing any facts that will tend to
lift the veil of mystery and thus destroy his greatest asset. So the
exploiter of nostrums to the medical profession, realizing that at
least a pretense must be made of giving the composition of medicaments
offered to the physician, declares that his clay poultice has for its
base “anhydrous and levigated argillaceous mineral.” This sounds much
more imposing than dry and finely powdered clay, and satisfies by its
very sonorousness. Now comes a product exploited chiefly to members
of the dental profession but also, it seems, to physicians. Tablets,
“activated tablets,” if you please! They are “an anodyne, analgesic
febrifuge sedative, exorcising [_sic!_] antineuralgic and antirheumatic
action.” And their composition? Simply “an activated, balanced
combination of the mono-acetyl-derivative of para-amidophenetol
together with a feebly basic substance in the alkaloidal state from the
Thea-Sinensis.” As clear as the Missouri River! Some day some dentist
or physician is going to investigate and find that this awe-inspiring,
polysyllabic example of exuberant verbosity means nothing more
mysterious than our old friends acetphenetidin (phenacetin) and
caffein. In the meantime, the exploiters may smile softly and murmur,
“Barnum was right!”--(_Editorial from The Journal A. M. A., Jan. 1,
1921._)
THE PHARMACOPEIA
The Ninth Decennial Revision
The ninth revision of the United States Pharmacopeia became official
this week, Sept. 1, 1916. It is more fully reviewed elsewhere;[303]
here we desire merely to call attention to two points; what the book
is and what it is not. It is a book of standards for drugs; it is
not a book of standard remedies. The Committee of Revision of the
Pharmacopeia included physicians and pharmacists (retail, wholesale
and manufacturing), but the pharmacists were in the majority and
in control. The majority of the representatives of the medical
profession on this committee would have preferred to see the bulk
of the Pharmacopeia reduced and its value as a work of reference
enhanced by the rejection of therapeutically worthless drugs. The
representatives of commercial interests, on the other hand, argued that
it was necessary for the Pharmacopeia to provide standards for drugs
in more or less general use, whether worthless or otherwise. The force
of this argument is somewhat impaired by the fact that the National
Formulary, which has also been made a book of legal standards, now
includes individual drugs as well as combinations; the new edition of
the Formulary, in fact, contains a large number of drugs which had been
dropped from the U. S. Pharmacopeia VIII. The principle of making use
the sole criterion for admission to the Pharmacopeia, however, on the
whole carried the day. It has not been strictly observed; good results
from the efforts of the medical contingent are to be observed here and
there, as in the deletion of elixir of the phosphates of iron, quinin
and strychnin and of emulsion of cod liver oil with hypophosphites.
That these instances were not expressions of policy on the part of the
Committee on Revision, but merely deviations from policy, may be seen
by a glance at the contents of the new Pharmacopeia. These include
substances which have been shown to be inert, like the hypophosphites
(calcium, potassium and sodium hypophosphites), complex and obsolete
mixtures, like the compound syrup of sarsaparilla, and drugs which
have been tried and found wanting, like saw palmetto berries. Even
substances seldom used by the medical profession, but chiefly or
altogether by the public, like sassafras, hops and peppermint (the
herb), are standardized and made official. It seems difficult to
discover any principle by which the sphere of the Pharmacopeia may be
definitely marked off from that of the National Formulary. There is
one great advantage in specifying U. S. P. drugs and preparations:
Physicians who do so invoke legal standards of purity and identity. The
only way to be sure of obtaining substances of therapeutic efficiency,
however, is to exercise discrimination. The Pharmacopeia is no guide.
Being prepared mainly by pharmacists to meet the needs of pharmacists,
the Pharmacopeia of course contains much matter of little interest to
physicians and entirely foreign to scientific medicine.--(_Editorial
from The Journal A. M. A., Sept. 2, 1916._)
[303] J. A. M. A. =67=:764 (Sept. 2) 1916.
Review of Ninth Revision
The ninth revision of the United States Pharmacopeia, which has been
in the hands of the Committee of Revision for more than six years, has
just appeared. As was to be expected, the desire of medical men on the
Committee of Revision to have therapeutic value made a requirement for
admission to the Pharmacopeia has not been fully realized; it remains
a book of standards for therapeutically good, bad and indifferent
remedies. Among the drugs of little or no therapeutic importance
or value are musk, arnica, eriodictyon, quassia, pumpkin seed, saw
palmetto berries, sarsaparilla and couch grass. Many superfluous
drugs and preparations are included. For instance, of the nine forms
of quinin described (quinin alkaloid, bisulphate, dihydrochlorid,
hydrobromid, hydrochlorid, salicylate, sulphate and tannate, and quinin
and urea hydrochlorid), at least four might well have been eliminated.
Two insoluble forms (the alkaloid and the tannate), two soluble forms
(the hydrochlorid and quinin and urea hydrochlorid), and a moderately
soluble form (the sulphate) are all that could reasonably be demanded
by even the most extreme partisans of the doctrine of “pharmaceutic
necessity.” Further, the use of quinin salicylate for its salicylic
acid content and of quinin hydrobromid for its bromid content is
unscientific. The inclusion of these salts in the Pharmacopeia is
regrettable.
Those interested in the promotion of rational therapy will also regret
the inclusion of a number of fluidextracts of violently toxic drugs,
such as aconite and gelsemium (dose 1/2 minim each), belladonna root,
digitalis, nux vomica and ipecac (dose 1 minim each), and lobelia (dose
2-1/2 minims). The more diluted forms, the tinctures, of these drugs
are preferable. The inclusion of such fluidextracts in the Pharmacopeia
is playing into the hands of certain pharmaceutical manufacturers, who
recommend the tincture be prepared from fluidextracts--an unscientific
procedure.
The efforts of the medical members of the committee, however, have
not been entirely fruitless. Of the articles described in the U. S.
Pharmacopeia VIII, 243 have been deleted; sixty-seven new articles have
been added. The loss of 167 titles may be set down as a gain. Moreover,
most of the new substances give promise of therapeutic usefulness.
Thirty-six are taken over from New and Nonofficial Remedies; nineteen
are substances which are in the edition of Useful Drugs now in the
press. It cannot be said, however; that all of the additions have been
judiciously selected. It is an infelicitous time to add calcium and
sodium glycerophosphate just when grave doubts of their therapeutic
efficiency are being felt. The addition of the extracts of aconite,
hydrastis and viburnum prunifolium is likewise unfortunate. All are
superfluous preparations, the first because a drug so powerful that
an average dose of the extract is only 10 mg. or 1/6 grain is better
given in the form of tincture; the second because hydrastis is a drug
of uncertain value, already represented by three preparations, and the
third because viburnum prunifolium has been discarded and discredited
by the best therapeutic authorities. It must be accounted clear gain,
on the other hand, that the deletions include many inert, obsolete
or superfluous substances like bismuth citrate, kaolin cataplasm,
pipsissewa, coca leaves, ladyslipper, wahoo, cotton root bark,
compound acetanilid powder and compound syrup of hypophosphites, not to
mention nine salts of iron and thirty-eight fluidextracts of various
drugs. Wines, unmedicated and medicated, whisky and brandy are also
among the articles dropped.
A number of new features are introduced, such as microscopic standards
for powdered drugs, standard abbreviations for titles, the use of
the term “mil” instead of “cubic centimeter,” and a chapter each on
sterilization, diagnostic reagents, biologic assays, electrolytic
determination of metals and the determination of alcohol, the melting
point, the boiling point and the congealing point.
The chemical nomenclature is substantially the same as that adopted in
the previous revision; so is the nomenclature of drugs. The addition of
official abbreviations for the Latin titles of drugs will doubtless be
found a useful feature.
Less commendable is the change from the familiar “Cc.” to “mil.” The
term “cubic centimeter” is so thoroughly established and so widely
used, wherever the metric system is employed, that it cannot be
expected that it will be universally displaced by the word “mil.” The
latter is therefore only a superfluous synonym, and as such out of
harmony with the simplicity of the metric system. Perhaps it may even
be taken for the abbreviation of “millimeter,” “milligram” or other
words derived from “mille,” which would be equally entitled to the same
abbreviation.--(_Book Review in The Journal A. M. A., Sept. 2, 1916._)
PHYSICIAN’S STOCK IN PRESCRIPTION PRODUCTS
The letter that follows comes from a physician who feels that he has a
grievance regarding a company in which he holds stock:
“In 1914, I bought some stock of the ---- ---- Company, and in 1917
bought some more stock in the same company. I notice that the company
advertises in The Journal of the American Medical Association, and I
believe it does this not so much to acquaint the medical profession
with its product, as to acquaint physicians with its name in order that
its stock salesmen can keep on unloading more stock to members of the
medical profession.
“The company gets the doctors’ money through the sale of stocks, it
gets its product on the market with the doctors’ assistance and through
their influence, and it looks to me as if the doctors were getting very
little in return, as the dividend checks have been few and far between
since I have known anything of the company.
“It is not my idea to criticize the product; but I do believe and feel
that the stockholders are entitled to a square deal from a company
which in turn is expecting so much from them, and again I feel that the
publishers of The Journal should be made aware of these conditions so
that they do not either consciously or unconsciously foster a concern
that is depriving the physician of his hard-earned money.
“If this letter is unfair, I am willing to be shown otherwise. Kindly
publish it in The Journal, omitting my name and address.”
The company to which our correspondent refers put out a proprietary
product prescribed by physicians and used by the public. Some years ago
the company in question advertised its product in The Journal until its
stock-selling scheme was brought to the attention of The Journal; the
advertisements were then rejected. Some years later, on evidence that
the company had discontinued its stock-selling methods to physicians,
its product was again admitted to the advertising pages of The Journal.
Our correspondent says that he believes that the physicians who hold
stock in this company “are entitled to a square deal.” What about the
public? Is it getting a square deal when physicians are financially
interested in the products that they may be called on to prescribe?
Is the average layman’s confidence in the medical profession likely
to be enhanced when he learns that the physician to whom he went for
treatment has a financial interest in the therapeutic agent which
was prescribed? Our correspondent’s complaint against the company
seems to be, not that the company sold stock to physicians, but that
“the dividend checks have been few and far between,” the assumption
being that had the dividends come regularly, there would have been no
complaint. It cannot be too often emphasized that it is against public
interest and scientific medicine for physicians to be financially
interested in the sale of products which they may be called on to
prescribe for the sick. It is perfectly true that there are many
physicians who would not consciously permit financial considerations
to warp their judgment; but it is not humanly possible to remain
unbiased in cases of this sort. It is conceivable that a judge on the
bench might make every effort to dispense impartial justice in a suit
in which one of the parties was a firm in which he, the judge, had
financial interest. Nevertheless, it would be obviously improper for
such a judge to try a case of this kind. Yet, in this supposititious
case the only harm that could result would be of a financial nature. In
the case of the physician, the harm is not to the public’s purse but to
the public’s health.--(_From The Journal A. M. A., Dec. 11, 1920._)
PITUITARY GLAND PREPARATIONS
The importance of the standardization of preparations of the posterior,
or infundibular, lobe of the pituitary gland (the liquor hypophysis
of the new United States Pharmacopeia, pituitary solution, pituitary
extract, etc.) is exemplified by a recent publication of Roth.[304] As
is well known, the active constituent or constituents of this gland
have not been isolated, and there is no chemical method of determining
the activity and therapeutic value of various preparations. There
are, however, certain physiologic methods by which the activity of
such preparations may be determined with a considerable degree of
exactness. The last revision of the Pharmacopeia, recognizing that
the best attested field of usefulness for such preparations is in
obstetrics, adopted as a test their activity on the uterus of the
guinea-pig; the details of the method adopted by the Pharmacopeia are
those described by Roth.[305] Roth now reports on the activity of
seven samples of commercial infundibular extracts, the products of
five American manufacturing pharmacists. Four of these samples were
found to be of Pharmacopeia strength; the other three were much weaker.
Of the latter, one had but one tenth, another but one fifth and the
third but one fourth of the required activity. Those preparations
which had been accepted by the Council on Pharmacy and Chemistry
for inclusion in New and Non-official Remedies corresponded to the
Pharmacopeia requirements. Roth also compared the activity of these
seven preparations on the blood pressure, another method by which
it has been proposed to standardize infundibular extracts. The four
preparations which were equally active on the uterus were found to be
equally active on the blood pressure; the other three were much weaker.
Roth points out, however, that the results of the two methods are not
necessarily parallel; in one instance, for example, two samples caused
equal rises of blood pressure, but one was twice as active as the other
on the uterus. Hence it is evident that the blood pressure test is not
a satisfactory method for determining the activity of a preparation on
the uterus, and vice versa.
[304] Roth, G. B.: Pituitary Standardization, Bull 109, Hyg. Lab.,
U. S. P. H. S., 1917.
[305] Roth, G. B.: Bull 100, Hyg. Lab., U. S. P. H. S.
The subject of pituitary standardization, or perhaps it may be said
the application of the present method is, however, in need of further
study. Thus the statement has recently been made[306] that commercial
preparations are on the market which have from three to five times
the activity of the Pharmacopeia standard; this was not the case,
however, with the preparations examined by Roth. It is probable that
some have used for comparison a weaker standard than that proposed
by the Pharmacopeia; this, of course, would lead to the conclusion
that the commercial preparations were stronger than the Pharmacopeia
standard. Roth suggests that the employment of standards of unequal
activity by the various supply houses could easily be eliminated by
having a central laboratory distribute material for use as a standard.
It will be recalled that before the United States Public Health Service
established and began the distribution of standards for diphtheria and
tetanus antitoxins, the commercial preparations of these varied even
more in activity than do those of the pituitary extracts at present.
[306] Pittenger, P. S., and Vanderkleed, C. E.: Jour. Am. Pharm. Assn.
=6=:131, 1917.
It is unnecessary to emphasize the importance of this subject; this is
sufficiently evident to those who have followed the recent clinical
literature on the use of pituitary extracts in obstetrics. These
preparations are used in times of emergency; a weak preparation is
valueless, whereas overdosage, either from too strong a preparation
or from too free use of a preparation of the official strength, is
often followed by disaster to the mother or child or both. Roth cites
a number of cases of ruptured uterus and other injuries resulting from
their use.--(_Editorial from The Journal A. M. A., May 5, 1917._)
PROPRIETORSHIP IN MEDICINE
_To the Editor_:--I am enclosing a reprint of my article on the
“Present Status of Pituitary Extract in Labor,” which appeared in The
Journal, June 2, 1917, p. 1601, and also the September issue of Parke,
Davis and Company’s _Therapeutic Notes_, on page 89 of which they quote
this article, that you may compare the two. The _Therapeutic Notes_
article is ostensibly a copy, but as a matter of fact, it gives it only
in part, which seems to me to be a gross misrepresentation, and one
which I do not think should go unnoticed.
Joseph J. Mundell, M.D., Anacostia, D. C.
[Comment.--_Therapeutic Notes_ is one of the house organs of Parke,
Davis and Company. A part of each issue is usually devoted to
“excerpts” from current literature. The _Therapeutic Notes_ may be
judged from the manner of “excerpting” the article of Dr. Mundell.
Naturally the interest of Parke, Davis and Company is in those sections
of the article which may be expected to promote the use of Parke, Davis
and Company’s proprietary preparation of pituitary extract--pituitrin.
The following passages from the article of Dr. Mundell were not among
those “excerpted” in _Therapeutic Notes_:
“Used here in properly selected cases, after due consideration by
one who has good obstetric judgment, its results are usually happy,
and it is a boon to the tired mother and her attendants.”
“To step beyond these narrow confines of indications is indeed
entering on dangerous territory. Especially is this true as regards
the life of the baby. It is recommended in small doses by some good
authorities and is frequently used in cases of slight contraction
at the brim with sometimes very good results if the birth occurs
within a few minutes, but frequently with disastrous results
to the baby if delivery is delayed. In such cases, forceps are
urgently indicated. Its use in such cases is risky beyond question.
Pituitary extract is recommended in cases of postpartum hemorrhage,
but ergot is undoubtedly to be preferred.”
“All means should be exhausted to arrive at a definite diagnosis,
and the dangers of its use should be fully appreciated and due
consideration given before its administration in any case, for such
a powerful drug, used indiscriminately, will surely produce sad
results to mother or child or both.”
“During the past two years a number of untoward effects and
consequences of severe character have arisen. As far as the
maternal accidents and complications are concerned, I firmly
believe that were the slogan of the hour “safety first” borne
in mind, a number of them could have been prevented, for beyond
question this drug has been greatly abused, as it has been given
in too large doses, in cases in which its use was strongly
contraindicated, and often, I am sorry to say, for no reason other
than the accoucheur’s expediency. Its use has been reckless and
careless. The many reports of its rapid and safe action have been
one of the greatest dangers. DeLee says, ‘It provides for the
physician and his brother gynecologist a lot of chronic sufferers,
often incurable, even after mutilating operations.’”
“An analysis of the detailed reports of all these cases of ruptured
uterus with one or two exceptions reveals the fact that pituitary
extract was abused, being given to patients who should not have
had it. To my mind, to give a dose of pituitary extract to a woman
who has a contracted pelvis, mild or severe, when the head has not
passed through the pelvis, is criminal and, if the obstetrician is
not aware of the contraction, he is still little short of being a
criminal.”
In the latter part of his article in The Journal, Dr. Mundell analyzes
the reports of twelve cases of rupture of the uterus, thirty-four cases
of fetal deaths, and forty-one cases of asphyxia pallida in which
“resuscitation was effected only after prolonged and vigorous efforts.”
These also were not excerpted.--Ed.]--(_Correspondence in The Journal
A. M. A., Nov. 24, 1917._)
The Manufacturer’s Protest
_To the Editor_:--The article in The Journal, November 24, page 1818,
on proprietorship in medicine does us a gross injustice, and in reply
thereto we beg leave to submit the following:
For reasons which every publisher (yourself included) understands,
it is not practicable for us to reproduce in full, in the columns of
_Therapeutic Notes_, all the clinical papers to which we wish to direct
the attention of our readers. But that the article of Dr. Mundell was
not garbled to make capital for Parke, Davis & Co. is quite apparent
on comparison of the omitted portions with a previous paper by the
same author, reprinted in the January (1917) issue of the _Notes_,
and herewith submitted together with clippings from other issues of
the _Notes_ which prove that we have not hesitated to present to our
readers the dangers incidental to the misuse of Pituitrin as well as
the advantages of its proper use.
_Therapeutic Notes_, in quoting other journals, puts into its readers’
hands the means of investigating the fairness of its quotations. It is
a house organ--true enough; but the organ of a house which has always
appealed to the honor as well as to the progressiveness of the medical
profession. Its publishers could not afford to resort to deception in
advertising their products, through this or any other medium.
The profession is indebted to Parke, Davis & Co. for Pituitrin (among
other medicaments), and it is to the profession that the manufacturers
look for the ultimate verdict. The contraindications are quite as
important as the indications, and, as the excerpts submitted show, we
have taken account of these, not only in forming our own estimate, but
in presenting the evidence to the readers of _Therapeutic Notes_.
We cite these facts that you may give us a square deal in an early
issue of The Journal if so disposed.
Parke, Davis & Co., Detroit.
[Comment.--The Journal has no desire to discuss Parke, Davis and
Company’s motives in omitting certain parts of Dr. Mundell’s paper.
What The Journal did was to publish those parts of Dr. Mundell’s paper
on the “Present Status of Pituitary Extract in Labor” that Parke, Davis
and Company left out of their circular. That it is not practicable,
as Parke, Davis and Company points out, for the manufacturers of
proprietary products to reproduce in full all clinical papers dealing
with such products is obvious. It is not so obvious why such concerns
in abstracting or quoting papers of this kind should delete those parts
that are unfavorable to the products dealt with rather than those
that are favorable. Curiously, however, whenever an author is quoted
only in part those parts are almost invariably those favorable to the
product.--Ed.]--(_Correspondence in The Journal A. M. A., Dec. 8,
1917._)
Why Proprietaries Flourish
_To the Editor_:--The following experiences seem to add one more to
the many reasons offered to explain why proprietaries and ready-made
preparations flourish at the expense of the official drugs and
preparations: A few days ago I prescribed Troches of Ammonium Chloride,
U. S. P., for a patient of exceptional perseverance. The next day he
had not yet secured the troches and told me that he had submitted the
prescription to seven pharmacies, including the largest, and three of
the best known and admittedly the best equipped in New York. All told
him that these troches were “not being made any more,” and that they
were therefore unable to supply him. He thereupon communicated with
one of the largest wholesale manufacturing pharmaceutical houses in
America and received precisely the same answer. I then took the matter
up with a first class pharmacist whom I knew and induced him to prepare
this difficult (!) troche, for which the U. S. Pharmacopeia gives
the following directions: “Rub the powders together until they are
thoroughly mixed; then form a mass with syrup of tolu and divide ...”
Seven pharmacists declined to fill a prescription for an official
preparation because they could not buy the preparation from a
wholesaler, and it required some persuasion to get the eighth to make
the preparation. But even worse, several of the pharmacists offered my
patient some ready-made troche more or less resembling the official, or
offered compressed tablets of ammonium chlorid.
That this is not an isolated example of what often poses as pharmacy
is shown by the fact that I have found it extremely difficult to find
a pharmacist who would extemporaneously coat pills with gelatin.
Most want the physician to alter his prescription so that one of the
ready-made gelatin coated pills can be dispensed, if a gelatin coating
is necessary. Some gelatin, hot water, a large cork, and a few domestic
sewing needles are all that is required for very satisfactory coating
of pills with gelatin, yet few pharmacists seem willing to perform this
simple procedure.
Two other illustrations, not so recent, have come to me from a
colleague. A few years ago he was unable to obtain from either of two
pharmacists an emulsion of cod liver oil without the hypophosphites
because, as both said, “It does not come without hypophosphites.”
On another occasion four of the best drug stores in Boston were
asked for the Compound Laxative Pill, U. S. P., then official in the
Pharmacopeia. In every case he was told that he must have meant the
compound cathartic pill, which in no way resembles the pill he sought.
With this attitude on the part of the men supposed to be serving the
public and the medical profession by the practice of pharmacy, is it
any wonder that it is difficult to induce the medical profession to
prescribe official preparations or combinations of official drugs in
place of ready-made commercial substitutes largely drawn from among the
proprietaries or specialties? Real pharmacy by real pharmacists is a
necessity if we are to succeed in combating the proprietary evil.
Cary Eggleston, M.D., New York.
--(_Correspondence in The Journal A. M. A., Aug. 21, 1920._)
PHILIP RAHTJEN AND HIS DISCOVERIES
Recent newspaper reports regarding the alleged “discovery of the Germ
of Pernicious Anemia” and the development of “an antitoxin and serum”
by Dr. Philip Rahtjen of Pasadena, California, have brought inquiries
of which the two that follow are typical. This from a physician in
Indiana:
“Please let me know about the supposed recent discovery of Dr.
Philip Rahtjen concerning pernicious anemia. The information I have
is from a newspaper clipping of October 21, Pasadena, California.
Kindly omit my name.”
A New York physician writes:
“If you could send me any information as to the enclosed I
would appreciate it. The article impresses one as absolutely
inconclusive. However, I promised the patient I would investigate
the matter.”
The enclosures referred to consisted of a reprint and a letter from
“Ph. Rahtjen, M.A., Ph.D.,” Pasadena, Calif., both of which had
been sent to a layman who had written to Rahtjen. The reprint was
a translation of a brief article by Rahtjen “On the Etiology of
Idiopathic Anemia,” translated from the _Centralblatt für Bakteriologie
Parasitenkunde und Infektionskrankheiten_. Rahtjen’s letter to the
layman read:
“Your inquiry relative to my isolation and classification of the
Germ of Anemia received.
“I herein enclose my paper published in August in the _Central
Magazine of Bacteriology_.
“I have succeeded in immunizing goats against the Germ therein
described. Five thousand injections of the Serum have been given.
Three hundred cases diagnosed as Anemia and Chlorosis were treated
under observation. Six cases of Pernicious Anemia were observed
under treatment. All responded favorably.
“The Serum is at your disposal from my laboratory here for the use
of your physician. The price is five dollars for twelve ampoules
each containing 1 ccm., the amount of one injection.
“The treatment consists of intramuscular injection every second day
accompanied with a nitrogenous free diet, preferably milk diet.
Your attending physician should very easily give them.”
Just what Rahtjen’s serum is we do not know. Nor have we been able
to find any information on the subject in any available medical
literature. In fact, a rather careful search of American medical
literature for some years past fails to reveal any article by Rahtjen
on any subject.
Philip Rahtjen is not a physician. In the Propaganda files is a
circular issued in 1917 by the “Rahtjen Tuberculosis Sanatorium” of San
Francisco, Calif. This exploits “The Rahtjen Cure for Tuberculosis” and
tells of “The Discovery of Dr. Philip Rahtjen.” The circular states
that:
“Dr Rahtjen studied in Heidelberg, Berlin, Munich, Marburg, and
Rostock, Germany, from which latter school in 1904, he graduated
in chemical pathology as Doctor of Philosophy. He became assistant
professor of pathology at the Imperial Biological Station at
Heligoland, and was later appointed assistant to Dr. Piorkowsky,
head of the _Deutsche Schutz und Heilserum Gesellschaft_.”
The same circular summarizes the potentialities of “Rahtjen’s Cure for
Tuberculosis” thus:
“The remedy seems to cure tuberculosis in all its forms with equal
celerity and certainty. The evidences indicate that it does not
matter how far the disease has progressed, if there be tissue
of the attacked organ remaining sufficient to sustain life, the
disease can be wholly eradicated and the patient restored to
health. This is indicated alike in tuberculosis of the lungs, of
the throat, of the bladder, of the kidneys.”
The booklet stated further that patients might be treated at one of two
places: at the offices of the sanatorium in the city of San Francisco,
or at the sanatorium itself near Glenwood. The cost of treatment at
the sanatorium was to be $1,000, which would entitle “the patient
to residence and attention there for four months.” According to the
leaflet, “This is regarded as a period sufficient to restore the
patient to health whatever be the stage of his disease; provided only,
as we remark, that he has enough left of the infected organ to sustain
life with the T. B. expelled.”
“At the end of four months the patient is sent to his home, not
alone relieved of his disease, but in a highly vigorous state of
health.”
All this, as stated previously, was in 1917. And yet people are still
dying of tuberculosis!
In March, 1920, Rahtjen (so the newspapers have it) was offering a
“New-Life Fluid.” According to a San Francisco paper, Dr. Philip
Rahtjen “announces the discovery that by the injection of secretions
from the ductless glands the human body may be reinvigorated.” The
paper described the discovery “as a long step forward in the fight
to counteract old age” and stated that a syndicate was being formed
by Rahtjen and others to “produce the extract in such quantity that
it may be available for every one.” The newspaper article showed the
learned doctor in a laboratory apron in the characteristic pose of
the newspaper “scientist” pouring something from a beaker into a test
tube--and gazing intently at the camera while doing it! This was in
March, 1920; yet people still grow old.
Within the last month the _Los Angeles Examiner_ has heralded some more
wonderful accomplishments of Rahtjen. According to this paper Rahtjen
has:
1. Isolated the “germ of pernicious anemia.”
2. Found the “serum” for the cure of this disease.
3. Discovered the secret of human virility.
4. Evolved a fluid “from the glands of selected bulls and cows” which
will “restore ‘pep’ for worn-out human bodies! Give added weight,
clearer eyes, brighter minds, quicker bodies and a generally ‘firmer
grip’ on oneself!”
This “amazing discovery” was, according to the Los Angeles paper, the
culmination of “five years of continuous study” and had only just been
revealed by Rahtjen.
“Dr. Rahtjen has for years been working silently in a bio-chemical
laboratory in Pasadena, surrounded by microscopes, scales,
test-tubes, acids, alkalis, reagents and all the accompanying stage
settings that spell bio-chemical science.”
All of these wonders might still have been a closed book to the public
had not “friends” of Dr. Rahtjen brought the matter to the attention of
the _Examiner_.
“Dr. Rahtjen yesterday, with the usual reserve of the ethical
scientist, was disinclined to talk of his work until publication of
it in a scientific journal.”
Fortunately for a palpitating public, the _Los Angeles Examiner_ “was
able to learn the essence of his study” and pass the information on. It
seems from this newspaper report that Rahtjen first made his extracts
from the glands of goats and sheep but these extracts “were found to
be too strong.” As a result “Dr. Rahtjen is now using the glands of
specially selected Mexican bulls and cows.” The male patients who are
“weak, uninterested in life, unable to concentrate in thought” are
given the extract of bull; the female patients who are in a similarly
deplorable condition receive an “injection of the cow gland extract.”
We have not yet learned whether the _Los Angeles Examiner_ has
deprecated Dr. Rahtjen’s use of Mexican bovines. Remembering the
attitude of the Hearst papers toward all things Mexican, one may look
for the suggestion that Mr. Rahtjen use 100 per cent. American
bull.--(_From The Journal A. M. A., Nov. 26, 1921._)
SODIUM CACODYLATE IN SYPHILIS
_To the Editor_:--I was much interested in the study of this subject by
Dr. H. N. Cole (The Journal, Dec. 30, 1916, p. 2012.)
In 1913 I treated a series of cases of syphilis with sodium cacodylate;
but, not getting the desired results, I discontinued its use. In 1915,
I became interested again because of the writings of Dr. J. B. Murphy,
and applied it in three cases in which the patients had initial lesions:
CASE 1.--J. M., man aged 21, single, shoeworker, came to me with
an initial lesion of the penis to the right of the frenum. I began
intramuscular injections of sodium cacodylate, 5 grains, in ampules
made by Parke, Davis & Co., every day for ten days. Then I halted
for ten days and repeated ten more injections. The sore on the penis
entirely disappeared about the ninth day. There was a slight, faintly
macular eruption of the forearms and abdomen, which soon disappeared.
There was no alopecia. When he returned, after the last series of
ten injections, there were mucous patches in the throat and some
involvement of the left tonsil. I put the patient on mixed treatment,
which cleared his throat. He had, at end of twenty doses of 5 grains of
sodium cacodylate each, a positive Wassermann reaction. After mercury
and potassium iodid for two months there was a positive Wassermann
reaction. To date, after three salvarsan treatments intravenously there
have been two negatives.
CASE 2.--F. S., man, aged 28, married, machinist, had an initial lesion
on the penis. Treatment with sixty injections of 5 grains of sodium
cacodylate gave results as follows: The initial sore on the penis
disappeared in ten injections; there were severe mucous patches of the
mouth; the tonsils were badly infected. There was a positive Wassermann
reaction. There were syphilids of both arms and shins; marked papular
eruption; malaise, and a slight trace of albumin in the urine. I
placed the patient on mercurials and at last give him three salvarsan
injections three weeks apart. The result was a negative Wassermann
reaction, the skin was clear and the patient felt fine.
CASE 3.--D. C., woman, aged 21, single, seamstress, had an initial
lesion on the left side of the cervix, and a macular eruption on the
face, neck and shoulders, and also, though faint, on the forearms.
Thirty injections of sodium cacodylate of 5 grains each were given. The
initial lesion disappeared in one week. Mucous patches of the mouth
appeared and persisted. The Wassermann reaction was positive. I gave
mercurials and potassium iodid for seven months, and salvarsan once.
The Wassermann reaction is now negative.
My conclusion after two trials of the use of sodium cacodylate in small
or large doses is that it has no effect toward curing the condition; in
fact, the throat symptoms were seemingly increased in severity by its
use. It has no effect on syphilids of the forearms and shins, and if
anything makes them worse.
It improves the appetite, as one would expect. It has some effect on
the kidneys, as noted in Case 2; it has some effect in healing the
initial lesion, as noted in all three of this series; why, I do not
know.
I am entirely satisfied that it has no beneficial effect on syphilitics
and have discontinued its use entirely in my practice.
I am glad to have read Cole’s excellent article, as it shows me that I
was correct in my decision not to use it again, as it was worthless.
William G. Ward, M.D., Lynn, Mass.
_To the Editor_:--Dr. William G. Ward’s letter (The Journal, Feb. 3,
1917, p. 390), and the recent admirable article by Dr. Harold N. Cole
(The Journal, Dec. 30, 1916, p. 2012) recall to mind Dr. J. B. Murphy’s
clinical note on the use of sodium cacodylate in the treatment of
syphilis (The Journal, Sept. 24, 1910, p. 1113), and the experimental
work of Cap. H. J. Nichols, U. S. Army (The Journal, Feb. 18, 1911,
p. 492). The results of Nichols’ work conclusively proved, at least
from a laboratory standpoint, that this drug was of very little value
as a spirocheticide in combating syphilis. Prior to the publication of
Dr. Murphy’s letter I had employed sodium cacodylate extensively as a
remedy in psoriasis, and I still continue to use it in selected cases
of the disease.
Adopting Dr. Murphy’s suggestion, I gave the agent an extensive trial
in syphilis in all stages of the disease. The results were extremely
disappointing, from both clinical and serologic points of view. More
recently, during the scarcity of salvarsan, I gave the drug a second
trial, employing it in large dosage in the hope that the previous
failure had been due to the employment of insufficient amounts. The
results were not tabulated, but, judging roughly from my experience in
a score of cases, its therapeutic value as an antisyphilitic was nil. A
few of the patients underwent a temporary improvement, probably owing
to the tonic effect of the drug, but in every instance the serologic
findings were unaffected.
R. L. Sutton, M.D., Kansas City, Mo.
--(_Correspondence in The Journal A. M. A., Feb. 3, 1917._)
TABLETS: DEPENDABILITY OF DOSAGE
The tablet form of administering medicines is popular among many
physicians because of its convenient availability and dosage. There
is no doubt about the convenience of tablets, but the accuracy of the
dosage content is not always to be depended on. One reason for this
is that the demand for palatable and convenient “medicaments has led
manufacturers to attempt to produce in tablet form mixtures which, from
the nature of the case, are not suited to that method of compounding.”
In a series of painstaking experiments[307] on bismuth, opium and
phenol tablets, conducted a number of years ago in the A. M. A.
Chemical Laboratory, it was shown that no tablets on the market then
contained the amount of phenol the label indicated, the variation
being from 12.3 to 112.5 per cent. Similarly, the laboratory found
that in the case of several different brands of Aromatic Digestive
Tablets,[308] the amount of hydrochloric acid present in these absurd
combinations was true to label in only one half of the specimens,
notwithstanding the fact that the amounts claimed to be present were
ridiculously small; in two specimens, there was no hydrochloric
acid whatever present, while a third contained only a trace. These
examples illustrated clearly the very evident unwisdom of attempting
the pharmaceutically impossible merely for the sake of convenience or
pharmaceutical “elegance.”
[307] Puckner, W. A., and Clark, A. H.: Examination of Tablets of
Bismuth, Opium and Phenol, The Journal A. M. A., July 25, 1908,
p. 330. Puckner, W. A., and Hilpert, W. S.: Tablets of Bismuth, Opium
and Phenol, Dec. 17, 1910, p. 2169, May 6, 1911, p. 1344. Unreliable
Pharmaceutical Products, editorial, May 6, 1911, p. 1335.
[308] Puckner, W. A., and Warren, L. E.: Aromatic Digestive Tablets,
The Journal A. M. A., Aug. 20, 1910, p. 710.
Another reason for doubting the accuracy of dosage, irrespective of
the characteristics of the drugs composing the tablets, has been the
manifest lack of care in their manufacture. In 1914, Kebler[309]
reported the results of a far-reaching investigation of tablet
compounding in which he pointed out that tablets on the market were
not as uniform or accurate as was generally believed, the variations
being “unexpectedly large in numbers and amount.” During the past year,
the Connecticut Agricultural Experiment Station[310] undertook the
examination of tablets--proprietary and nonproprietary--taken from the
stock of dispensing physicians. The variations found in _weights_ of
the tablets were strikingly similar to those reported by Kebler.
[309] Kebler, L. F.: The Tablet Industry, Jour. Am. Pharm. Assn., 1914,
3, 820, 937, 1062.
[310] Bull. 200, Connecticut Agricultural Station, Food and Drug
Products, 1917, p. 161.
VARIATION IN WEIGHTS OF TABLETS
Kebler Connecticut
Variation Per Cent. Per Cent.
Less than 10 per cent. 43 44
More than 10 per cent. 57 56
More than 12 per cent. 44 35
More than 15 per cent. 28 26
More than 20 per cent. 9 10
The determinations of the _composition_ of the tablets when compared
with that claimed for them showed wide variation--from 54 per cent.
above to 70.5 per cent. below; in almost two thirds of the tablets
examined, the variation amounted to more than 10 per cent.; in three
fifths of the tablets, the variation was more than 15 per cent.; in one
fourth, more than 20 per cent., and in one twentieth, more than 50 per
cent.; only in one eighth of the tablets was the variation less than 5
per cent.
The Connecticut investigators substantiate once again the work
previously reported, namely, that there are a number of firms who are
either incompetent or careless. For tablets of simple composition,
a variation from the declaration of 10 per cent. should be amply
sufficient to compensate for the errors of careful manufacture. It may
be added that the best tablets originate generally from firms having
competent chemical control.--(_From The Journal A. M. A., July 27,
1918._)
THERAPEUTIC EVIDENCE: ITS CRUCIAL TEST[O]
Torald Sollmann, M.D., Cleveland
[O] Read before the Section on Pharmacology and Therapeutics at the
Sixty-Eighth Annual Session of the American Medical Association, New
York, June, 1917.
[O] This article clearly states the difficulties experienced by the
Council in estimating the merits of a proprietary medicinal product
and clearly defines the method which has been found to be practical in
judging of the therapeutic value of such preparations. The Council has
approved this discussion of the subject and has directed that the paper
be published in the annual Council reports.
W. A. Puckner, Secretary.
According to the good old truism, the last and crucial proof of the
pudding is in the eating thereof; and so, the last and crucial test of
a therapeutic agent is its consumption by a patient. There is, however,
one essential difference: When the pudding is eaten, with a sense of
satisfaction, we know that it was a good, or at least an eatable,
pudding.
If the patient improves after taking a remedy, we do not yet know
that he improved on account of the remedy. The _post hoc_ type of
reasoning or logic is not respectable; but it is all too apt to creep
in unawares, unless one takes great precautions indeed.
Clinical evidence needs especially to be on its guard against this
pitfall, for the conditions of disease never remain constant; nor is it
possible to foresee with certainty the direction which they are going
to take. It is just this point which makes the clinical evidence so
much more difficult to interpret than laboratory evidence, in which
the conditions can be more or less exactly controlled, and any changes
foreseen. It is on this account, also, that clinical experiments must
be surrounded with extra painstaking precautions.
In brief, while the “proof” of a remedy is on the patient, that is not
the whole story, but merely an introduction. The real problem is to
establish the causative connection between the remedy and the events.
The imperfect realization of this has blocked therapeutic advance, has
disgusted critical men to the point of therapeutic nihilism, and has
fertilized the ground for the commercial exploitation of drugs that are
of doubtful value or worse.
This has been impressed on me particularly by my service on the Council
on Pharmacy and Chemistry. In the course of its work of passing on the
claims advanced for commercial remedies, this Council is forced to
inquire critically into the basis of the claims of manufacturers.
It is interesting to note the qualitative differences in the evidence
for the various kinds of claims: The chemical data are usually
presented in such a form that it is possible to tell at a glance
whether or not they are based on demonstrated facts, which could
usually be verified or refuted without special difficulty. The
deductions are usually such as can be legitimately drawn from the data,
or else they are obviously absurd. All this agrees with the relatively
exact status of chemical science.
In passing to data and deductions from animal experiments, a distinct
change is noticeable: Not only are the data less reliable, and less
worthy of confidence, but they are more often stated in a less
straightforward manner. The presentation of the data often shows
evidence of manipulation of the results, so as to make them most
favorable to a preconceived conclusion that would recommend the drug.
This is not always intentional, but is partly due to the less exact
nature of animal experimentation, which leaves a wider play to the
arbitrary interpretation of the reporter. A certain amount of this
is unavoidable. No serious objection can be raised, provided the
experimenter presents all the essential data, and discusses fairly all
of the interpretations that would apply to them.
On the whole, it is usually possible to form a fairly definite estimate
of the value of experimental data.
When one comes to the clinical evidence, an entirely different
atmosphere obtains. When the Council demands evidence of the usefulness
of a remedy, the manufacturers generally respond with every sign of
enthusiasm. They may have ready a series of articles already published,
or they instruct their agents to bring in letters from physicians. The
last method seems to meet the most cordial response, judging from the
deluge of letters and opinions that floods the Council.
The quality of the published papers is a fair reflection of the
deficiencies of what is still the common type of clinical evidence.
A little thought suffices to show that the greater part cannot
be taken as serious evidence at all. Some of the data are merely
impressions--usually the latest impressions of an impressionable
enthusiast--the type of man who does not consider it necessary to
present evidence for his own opinions; the type of man who does not
even realize that scientific conclusions must be based on objective
phenomena.
Some of the papers masquerade as “clinical reports,” sometimes with a
splendid disregard for all details that could enable one to judge of
their value and bearing, sometimes with the most tedious presentation
of all sorts of routine observations that have no relation to the
problem.
The majority of reports obtained by the agents belong to these classes,
notwithstanding the fact that they are often written for the special
use of the Council, and therefore with the realization that they
are likely to be subjected to a thorough examination, and therefore
presumably representing the best type of work of which the reporter is
capable. So, at least, one would suppose.
It is also possible, however, that some of these reports are written
merely out of thoughtlessness, or perhaps often to get rid of an
importunate agent. This is illustrated by the following correspondence,
taken literally from the files of the Council.
A letter from a prominent physician “A,” endorsing a certain
preparation “D,” having been submitted to the Council, the secretary
was directed to write to Dr. A as follows:
_Dear Dr. A_:--The B Company of C has requested the Council on Pharmacy
and Chemistry to admit its preparation D to New and Nonofficial
Remedies. As part evidence for the value of the preparation, the
company submitted a letter from you which contains the following:
So far as my experience has thus far gone, they are certainly
superior to a number of other iodine compounds now on the market,
and I should judge that they ought to take a superior place in
therapy involving the use of iodine.
The referee of the Council in charge of D writes that he was interested
by your letter and asks that I inquire: As compared with sodium or
potassium iodid, what would you say are the differences between,
and real advantages of, D and the alkaline iodids? Did you make any
comparative experiments and keep a record of them? If so, the referee
would like to receive an account of your trials. In what direction
could D be expected to occupy a superior place in iodin therapy?
I hope that you can give the information asked by the referee and
thus aid the Council in arriving at a correct estimate regarding
the value of D.
The following reply was received from the physician in response to the
foregoing:
_Dear Professor Puckner_:--In reply to yours of January 19, I
did not proceed far enough in the investigation of D to draw
conclusions of any particular value for the purpose of the Council
on Pharmacy and Chemistry; and I so stated in my letter to the
proprietors of that remedy.
Answers to the questions you put in your letter require an amount
of investigation of the remedy far beyond anything I undertook.
As a matter of fact, I returned about five sixths of the capsules
sent me, because of lack of time and opportunity to carry out the
extensive clinical experiments that I plainly saw would be required
to give an opinion at all worth while. I believe you had better not
consider me in the matter at all.
The report was furnished by a physician for whom I have a high personal
regard. I introduce it here, not so much in a spirit of criticism,
but as a justification of the opinion that I have formed of clinical
evidence obtained by manufacturers through their clinical adjutors.
When commercial firms claim to base their conclusions on clinical
reports, the profession has a right to expect that these reports
should be submitted to competent and independent review. When such
reports are kept secret, it is impossible for any one to decide what
proportion of them are trustworthy, and what proportion thoughtless,
incompetent or accommodating. However, if this were done it is quite
possible that such firms would find much more difficulty in obtaining
the reports. Those who collaborate should realize frankly that under
present conditions they are collaborating, not so much in determining
the scientific value, but rather in establishing the commercial value
of the article.
Often the best type of clinical reports--those in which the
observations are directed to the significant events and not to mere
side lines, and in which the significant events are correctly and
adequately reported--generally lack one important essential, namely, an
adequate control of the natural course of the disease.
Since this cannot be controlled directly, it must be compensated
indirectly. For this purpose, there are available two methods:
The first is the statistical method, in which alternate patients
receive or do not receive the treatment. This method can usually
only be of value when a very large series of patients is available.
Even then, its value is limited or doubtful, because it cannot take
sufficient account of the individuality of cases.
The second method consists in the attempt to distinguish unknown
preparations by their effects--the method that might be called the
“comparative method” or the “blind test.”
In this, the patient, or a series of patients, is given the preparation
which is to be tested, and another preparation which is inactive,
and the observer aims to distinguish the two preparations by their
effects on the patient. Surely if the drug has any actions at all it
will be possible to select correctly in a decided majority of the
administrations.
The same principle can be applied in distinguishing the superiority
of one preparation over another. In this case, the two preparations
would be given alternately to different patients, and the observer
would try to distinguish them by their effects. Here again, if one
drug is really superior or otherwise different from another, to a
practically important extent, the observer will surely be able to make
the distinction.
This method is really the only one that avoids the pitfalls of clinical
observation; it is the only method that makes the results purely
objective, really independent of the bias of the observer and the
patient. It is the only method, therefore, which determines whether it
was really the pudding that was eaten and not some other dessert.
In principle this method does not usually offer any very great
difficulties. It is, of course, necessary that the two preparations
to be compared shall resemble each other so closely or shall be
flavored, etc., so that they cannot be distinguished by their physical
properties. This is usually not a very difficult matter. The method
does not jeopardize the interests of the patient, for it is understood
that no drug would be tested in this way unless there is some reason
to believe that it has a value. When the patient’s condition is such
as to demand treatment, then he would be receiving either the standard
drug or the drug which the experimenter believes may be superior to the
standard.
CONCLUSIONS
The final and crucial test of a remedy is on the patient; but the
test must be framed so as to make it really crucial. Most clinical
therapeutic evidence falls far short of this. The “blind test” is urged
to meet the deficiencies.--(_From The Journal A. M. A., July 21, 1917._)
“VACCINES IN TOXIC CONDITIONS”
Commercialized Propaganda in the Guise of Science
Under the title “Vaccines in Toxic Conditions,” what purports to be
a scientific contribution appears in the original department of the
official organ of a state medical society.[311] The apparent purpose of
the article is to overcome any hesitancy on the part of practitioners
to use vaccines in toxic infectious conditions for fear that they
might thereby cause harm. Such a thesis is interesting and might be
important--if true. Two outstanding facts, however, give pause. First,
the theory promulgated is contrary to the experience of those who
have studied the subject; second, the man who writes the article is
in the business of making and selling vaccines! The former fact is a
matter of fairly general knowledge among the better informed members
of the medical profession; the latter fact is nowhere made evident in
the article, which the reader might infer came from a disinterested
investigator in the realms of immunology.
[311] Sherman, G. H.: Vaccines in Toxic Conditions, Illinois M.J. 38:
314 (Oct.) 1920.
The article purports to prove that the special investigations carried
on by its author show that there is no basis for the well-grounded
fear that vaccines might be harmful to a patient suffering from toxic
infectious conditions. Thus:
From a closer study of these infective processes we find that this
toxic condition is due to the rapid multiplication of the infecting
organisms with the incidental production of ferments which the
germs secrete to digest the food on which they live. These toxic
ferments have a distinct destructive tendency on tissue cells,
without any marked influence in stimulating tissue cells for
antibody production. The crying need, however, in these extensive
acute infections is rapid antibody formation to neutralize these
germ-produced poisons and to eliminate the germs.
Now vaccines, we are informed, are not toxic and so stimulate the
production of antibodies. In other words, the same organism that in
the body is toxic and without marked antigenic properties becomes
nontoxic and actively antigenic when converted into a vaccine. The
details of the experiments of the “closer study” made by the author of
this paper (and the manufacturer of vaccines) which give such definite
and convincing results are not published. Possibly the article is a
preliminary contribution, and future issues of the same publication
will carry further articles on the same subject. The follow-up system
is well recognized in the advertising world. At all events, this
“closer study” has convinced the author of the article that:
... even in extreme toxic conditions, in acute infections,
bacterial vaccines may be employed without the least fear of doing
any harm. In fact, we find that in extreme acute infections,
bacterial vaccines not only give the best clinical results, but
they may also be given in larger doses at shorter intervals with
less reactions than in minor or chronic infections and the earlier
they are given the better the results.
Here again no details are given; there are no comparative results of
the careful study of a series of cases. The sum and substance of this
remarkable contribution to a scientific publication is to the effect
(1) that the organism that in the body is toxic becomes nontoxic when
introduced in vaccine form; (2) that the organism that in the body is
but little antigenic becomes when introduced in vaccine form actively
antigenic, and (3) that “in extreme acute infections” when the body
is affected profoundly by the infectious agent and its product, the
oftener and the more one injects of these very materials, the better
the results!
And this astounding plea for the use of vaccines in conditions in which
vaccines are generally held to be contraindicated, or even injurious,
is made by one whose business is the manufacture of vaccines and
selling them to the medical profession!--(_Editorial from The Journal
A. M. A., Oct. 23, 1920._)
VITAMINS: THEIR DISTRIBUTION
Our knowledge of the accessory food factors, commonly spoken of
as vitamins, is so recent, comparatively speaking, and the exact
nature of these factors still so enveloped in mystery, that it was
inevitable that the public’s lack of knowledge on the subject should be
capitalized. It is not surprising that there are on the market a number
of preparations of the “patent medicine” type that are being sold under
the claim that they are rich in vitamins--although the exploiters
of these fail to explain which, if any, of the three accessory
food factors their products contain. The renaissance of yeast as a
therapeutic agent has given an opportunity to the manufacturers of this
product of unduly stressing the fact that yeast is particularly rich in
the antineuritic vitamin (water-soluble B). Because milk and certain
milk products are rich in the fat-soluble A factor, the dairy interests
would apparently have the public believe that this particular vitamin
is to be obtained only from their products. Thus, a journal devoted to
the dairy interests recently claimed that those who want vitamins must
get them in their milk, butter, cheese and other milk products. The
truth is, the accessory food factors are so well distributed throughout
the dietary of modern man that, generally speaking, the individual
who uses ordinary judgment in selecting his food is in no danger of
suffering from a deficiency of any of these three factors. It would
be well if every physician might read the excellent monograph on the
present state of knowledge concerning accessory food factors written
by a committee appointed jointly by the Lister Institute and Medical
Research Committee. In this report the distribution of the vitamins in
our common foodstuffs is thus briefly summarized: “... broadly speaking
it is safe to say that the individual always finds sufficient supply
of vitamins in his food so long as that food is reasonably varied and
has received no artificial or accidental separation into parts, and so
long as no destructive influence has been applied to it.” At the end
of the committee’s report is a table (reproduced on page 562) which
shows the distribution of the three accessory factors in the commoner
foodstuffs.--(_Editorial from The Journal A. M. A., Aug. 13, 1921._).
DISTRIBUTION OF THREE ACCESSORY FACTORS IN COMMONER FOODSTUFFS
Classes Fat-Soluble A Water-Soluble B Anti-
of or Anti- or Antineuritic scorbutic
Foodstuff rachitic (Antiberiberi) Factor
Factor Factor
_Fats and Oils_:
Butter +++
Cream ++
Cod-liver oil +++
Mutton fat ++
Beef fat or suet ++
Peanut oil +
Fish oil, ++
whale oil, etc.
Margarin prepared Value in
from animal fat proportion to
amount of
animal fat
contained
Nut butters +
_Meat, Fish, etc._:
Lean meat (beef,
mutton, etc.) + + +
Liver ++ ++ +
Kidneys ++ +
Heart ++ +
Brain + ++
Sweetbreads + ++
Fish, white very slight,
if any
Fish, fat (salmon,
herring, etc.) ++ very slight,
if any
Fish roe + ++
Canned meats ? very slight
_Milk, Cheese, etc._:
Milk, cow’s whole, raw ++ + +
Milk, skim, raw + +
Milk, dried whole less than ++ + less than +
Milk, boiled, whole undetermined + less than +
Milk, condensed,
sweetened + + less than +
Cheese, whole milk +
_Eggs_:
Fresh ++ +++ ?
Dried ++ +++ ?
_Cereals, Pulses, etc._:
Wheat, maize, rice,
whole grain + +
Wheat germ ++ +++
Wheat, maize, bran ++
Linseed, millet ++ ++
Dried peas, lentils,
etc. ++
Soy beans, haricot beans + ++
Germinated pulses or
cereals + ++ ++
_Vegetables and Fruits_:
Cabbage, fresh (raw) ++ + +++
Cabbage, fresh (cooked) + +
Cabbage, dried + + very slight
Cabbage, canned very slight
Swede (rutabaga) raw
expressed juice + +++
Lettuce ++ +
Spinach (dried) ++ +
Carrots, fresh raw + + +
Carrots, dried very slight +
Beetroot, raw,
expressed juice less than +
Potatoes, raw + +
Potatoes, cooked +
Beans, fresh, scarlet
runners, raw ++
Onions, cooked + at least
Lemon juice, fresh +++
Lemon juice, preserved ++
Lime juice, fresh ++
Lime juice, preserved very slight
Orange juice, fresh +++
Raspberries ++
Apples +
Bananas + + very slight
Tomatoes (canned) ++
Nuts + ++
_Miscellaneous_:
Yeast, dried +++
Yeast, extract and
autolyzed ? +++
Malt extract + in some
specimens
Our Knowledge of Vitamins
Commenting on the trend of medical research concerning vitamins, the
latest report of the British Medical Research Council says:
The present situation is a curious one, upon which posterity will
probably look back with great interest. We still have almost no
knowledge of the nature of these elusive food substances or of their
mode of action, but we have gained empiric knowledge already of the
greatest practical value for the prevention of scurvy and of other
grave diseases and for the promotion of health and beauty in the
population.
This statement, it will be noted, emphasizes the foundation on which
rests our present use of vitamins. From time to time The Journal
has commented on our lack of actual knowledge of these mysterious
substances, emphasizing particularly the generally accepted fact that
the taking of a well-balanced diet results in providing the individual
with such vitamins as are necessary to his growth and nutrition. Last
week appeared a brief report of a meeting of the Chicago Medical
Society devoted to this subject, and it was gratifying to have the
conservative view which The Journal has emphasized substantiated by
many of those who took part in the discussion. Moreover, the _British
Medical Journal_, in its leading editorial for February 11, reiterates
that an abundant supply of vitamins exists in all fresh vegetables,
and that a considerable quantity occurs in milk and meat, provided
the latter substances are obtained from animals fed on fresh foods.
“A normal adult,” it says, “living on an ordinary diet containing a
reasonable proportion of fresh vegetables is, therefore, certain of
obtaining a plentiful supply of vitamins.” Of all the mass of evidence
which has accumulated relative to these substances, this fact is the
point of greatest importance. It is, however, very unfortunately,
the one point which those commercially inclined are unwilling to
recognize.--(_Editorial from The Journal A. M. A., March 11, 1922._)
The Demand for Vitamins
Thus the _British Medical Journal_ in its current issue:
In spite of the fact that ordinary fresh foods are the simplest,
cheapest and richest sources of vitamins, the public apparently demands
to be supplied with vitamins in the form of medicinal products.
The public “demands” vitamins in pill form! Why? For the same reason
that the public, lay or medical, demands many things today that it
does not need--because the whole trend of modern advertising is toward
creating demands, rather than supplying needs. Vitamin concentrates
are being “demanded” by the public because shrewd and forward-looking
“patent medicine” exploiters are using all the subtle arts of modern
advertising to convince the public that it is in serious danger of
vitamin starvation, and that the only hope lies in buying these
alleged concentrates to make up a hypothetical deficiency. It seems
inconceivable that a rational man would pay a tremendously high price
for certain food factors which are already present in his ordinary
diet. But he will; and advertising is the reason. Advertising
campaigns such as these of the vitamins constitute a vicious circle;
an artificial demand is created and then the manufacturer excuses his
business on the ground that he is merely supplying a demand! As our
British contemporary says, “ordinary fresh foods are the simplest,
cheapest and richest sources of vitamins.”--(_Editorial from The
Journal A. M. A., March 18, 1922._)
THE WILLIAM A. WEBSTER CO. AND THE DIRECT PHARMACEUTICAL CO.
The following letter from a Detroit physician was received a few days
ago.
_To the Editor_:--I have just received a letter from the Direct
Pharmaceutical Co. of St. Louis, Mo., quoting prices on drugs
which are not more than one half what the leading manufacturers
are quoting on the same drugs. I have received previous literature
from this company but have not done business with them. I would be
unwilling to prescribe their drugs unless I were satisfied that
they are what is claimed for them. I would be glad to receive any
information regarding this firm that may be available.
The Journal has also received some letters from physicians regarding
the William A. Webster Co. of Memphis, Tenn., relative to a letter the
concern was sending physicians in the form of a testimonial (reproduced
in miniature on this page) and alleged to be from Dr. F. W. P. Butler
of Columbia, S. C. Typical letters on the Webster advertising follow:
_To the Editor_:--Is there not some way through which the dignity
of the medical profession can be protected from the circulation of
such idiotic drivel as the enclosures display?
_To the Editor_:--I am sending you an example of the sort of
“evidence” which some so-called ethical pharmaceutical houses
expect physicians to take for scientific proof. It is pathetic that
there are some in our profession who “fall for” such rot. I trust
you will continue your campaign for honest and intelligent medicine.
The “evidence” to which one of the correspondents refers and which
another characterizes as “idiotic drivel” is reproduced on the
following page in miniature. It is a testimonial for William A. Webster
Company’s “Ferritonic-Woods.”
Our readers may wonder why we are discussing in one article the William
A. Webster Company of Memphis, Tenn., and the Direct Pharmaceutical Co.
of St. Louis. The reason is that the Direct Pharmaceutical Co. of St.
Louis is apparently merely a sales agency for the William A. Webster
Company of Memphis. It appears that orders sent in to the Direct
Pharmaceutical Co. go to Memphis to be filled.
The following information regarding some of the products that have
in the past been put out by the William A. Webster Company should be
of interest to the profession. In government bulletins issued by the
Department of Agriculture in October, 1913, there were reported some
cases of adulteration and misbranding on the part of the William A.
Webster Co., of Memphis, Tenn. A “Pure Concentrated Extract of Lemon”
shipped by this concern was found by the federal chemists to be colored
with a coal-tar dye “whereby inferiority was concealed,” and while
purporting to be a concentrated lemon extract, “in fact, it was not a
concentrated lemon extract.” Some “Pure Concentrated Extract of Banana”
was found to have mixed with it an imitation banana flavor and an
artificial color so as to “injuriously affect its quality and strength”
and so that “its inferiority was concealed.” “Pure Concentrated
Extract of Pineapple” was found to have had mixed with it “an imitation
extract of pineapple artificially colored.” “Pure Concentrated Extract
of Strawberry” had been mixed with “an imitation strawberry extract
artificially colored.” The same bulletins described the case of the
government against a shipment of “Syrup Iron Iodide” made by the
Webster concern in which the amount of iron iodid was less than half
that claimed on the label. In each of the cases just described, the
company pleaded guilty and was fined.
[Illustration: Reproduction (reduced) of a testimonial letter sent to
physicians by William A. Webster Company of Memphis, Tenn. Those who
operate this concern also have a sales agency in St. Louis, Mo., known
as the Direct Pharmaceutical Co.]
In a similar bulletin issued August, 1914, there were recorded several
more cases of adulteration and misbranding charged against the William
A. Webster Company. Some “Wine Coca Leaves” was held adulterated in
that the amount of alcohol present was wrongly declared on the label;
it was held misbranded in that while it contained cocain, the label
failed to bear any statement regarding the quantity of proportion of
this drug. Tablets of “Acetanilid and Sodium Bromid Compound” were
found deficient in strength. “Anti-Vomit Tablets,” “Aspirin Tablets,”
“Bismuth and Calomel Tablets,” “Quinin Laxative Tablets,” “Salol
Tablets,” “Sodium Salicylate Tablets,” “Neuralgic Tablets,” “Diarrhea
Calomel Pills” and “Morphin Sulphate Hypodermic Tablets” were also
misbranded in that the amount of certain ingredients found in them
failed to tally with the amount declared on the label. In all of these
cases also the William A. Webster Company pleaded guilty and was fined.
In a government bulletin issued in June, 1917, the same company was
charged with adulterating and misbranding a quantity of Aspirin tablets
which, instead of containing 5 grains as labeled, contained only a
fraction over 1 grain. In this case, too, the company pleaded guilty
and was fined. The table that follows briefly summarizes some of the
cases just referred to:
Amount Claimed Amount Found
“Syrup Iron Iodid, U. S. P.”
Ferrous Iodid 10% 4.6%
“Acetanilid and Sodium Bromid Tablets”
Acetanilid 3.50 gr. 2.94 gr.
“Anti-Vomit Tablets”
Bismuth subnitrate 2.50 gr. 1.76 gr.
Cerium Oxalate 2.50 gr. 1.78 gr.
Cocain Hydrochl. 0.0833 gr. 0.0637 gr.
“Aspirin Tablets” 5.0 gr. 3.82 gr.
“Bismuth and Calomel Comp. Tablets”
Bismuth subnitrate 0.1 gr. 0.22 gr.
Calomel 0.1 gr. 0.22 gr.
“Quinin Laxative Tablets”
Acetanilid 2.0 gr. 1.69 gr.
“Salol Tablets” 2.50 gr. 2.05 gr.
“Sodium Calicylate Tablets” 5.0 gr. 3.88 gr.
“Neuralgic Pills”
Morphin sulphate 0.05 gr. 0.015 gr.
“Diarrhea Calomel Pills”
Morphin sulphate 0.062 gr. 0.05 gr.
“Morphin Sulphate Hypodermic Tablets” 0.25 gr. 0.21 gr.
“Aspirin Tablets” 5.00 gr. 1.13 gr.
X/
--(_From The Journal A. M. A., Oct. 18, 1919._)
YEAST
From time to time yeast has attained a transitory popularity as a
therapeutic agent. Its use in this way in practical medicine has been
based essentially on empiric considerations. Yeast is rich in nucleic
acid, but this has not found any special applications. The fatlike
substances obtainable from yeast have been recommended in certain
alimentary conditions, without finding any widespread acceptance.
More recently yeast has acquired interest from somewhat different
angles. In these days of food shortage and enforced conservation,
it has come to be realized that the minute yeast cells are endowed
with a remarkable capacity of synthesizing one of the most valued
nutrients, namely, protein. This substance can be built up out of the
simplest forms of nitrogenous compounds by yeasts, in contrast with
the incapacity of the higher organisms to construct protein out of
anything less complex than the ready made aminoacids. It is reported
that in Europe yeast has actually been grown on a large scale in
solutions of sugar, salt and simple nitrogenous compounds for the
sake of securing the much desired proteins. The utilization of yeast
protein for cattle feeding is a current practice abroad; and the
satisfactory digestibility and availability of the same product by the
human organism has repeatedly been announced since the beginning of
the war. In this country the yeast which is produced as a by-product
of the brewing industry is for the most part discarded as waste; in
the distilleries it becomes a part of the distillers’ grains that are
extensively employed as feeds in the dairy industry.
Still newer is the indication that yeast is comparatively rich in at
least one of the as yet unidentified accessory factors in nutrition
now popularly spoken of as vitamins. Hopkins of the University of
Cambridge, England, first directed attention to this unique property of
yeast. It has been verified by Funk and Macallum, and recently Osborne
and Mendel have given substantial evidence of the potency of yeast to
render a diet not otherwise capable of inducing maintenance effective
in nutrition.
Yeast has been used, like extracts of rice polishings, to cure the
experimental polyneuritis induced in birds by a diet of polished rice.
From the experiments of Osborne and Mendel it appears that less than 2
per cent. of dried brewers’ yeast suffices to induce small experimental
animals to grow on artificial food mixtures on which alone they fail
to thrive. How the use of yeast as an adjuvant to otherwise inadequate
food mixtures exerts its beneficial effect is not yet made clear.
Satisfactory growth in these cases is promoted by liberal eating.
Anything which renders food more palatable may stimulate one to eat
more liberally of it. This can scarcely be the explanation of the
potency of the yeast as it is effective even when fed apart from the
rest of the food. It may have a favorable effect on the metabolism and
thus improve the general condition so that more food is consumed. Small
quantities of milk and extracts of many of the common plant foods,
such as the cereal grains, have been found to act in the same way.
There seems to be little doubt, therefore, that yeast also contains
something comparable with the so-called water-soluble vitamins of the
diet. A specific need for yeast can scarcely be predicated on this
fact, however; for any well selected human dietary containing the usual
variety of animal and vegetable foods is not likely to be devoid of
the widely distributed water-soluble type of vitamin. We mention this
to check premature enthusiasm for a new vitamin.--(_Editorial from The
Journal A. M. A., Sept. 8, 1917._)
Yeast and Its Uses
_To the Editor_:--Is there available information concerning the
medicinal use of yeast? How is it taken? I should like to know
whether the use of it would cause any digestive disturbance, and
whether the flesh gained is normal and permanent.
S. E. L., Bridgeport, Conn.
ANSWER.--Yeast is one of those remedies that have undergone alternating
cycles of use and of disuse; just at present it appears again to be
in its ascendency. No doubt, the reason for these cycles has been
excessive praise and uncritical use, followed by disappointment and
consequent discard.
Hawk and his associates (Hawk, P. B.; Knowles, F. C.; Rehfuss, M. E.,
and Clarke, J. A.: The Use of Bakers’ Yeast in Diseases of the Skin and
of the Gastro-Intestinal Tract, The Journal, Oct. 13, 1917, p. 1243)
have recently called renewed attention to its laxative qualities.
When from one-half to one cake of yeast was given three times daily
before meals, it produced regular bowel movements in a number of
patients suffering from constipation. That this result is not due
to any vital processes in the yeast is shown by the fact that yeast
killed by boiling water was employed with success. It is suggested that
such yeast might be preferred for patients troubled with flatulence.
Aside from the tendency of living yeast to produce diarrhea, and the
possibility that it may aggravate flatulence, no digestive disturbance
has been charged against it. Aaron, in his “Diseases of the Digestive
Organs,” speaks favorably of its use in atonic constipation.
The much debated question whether yeast may serve as a food can be
answered in the affirmative in view of such work as that of the Germans
on “Nährhefe”--yeast food (Schottelius, _Deutsch. med. Wchnschr._, July
8, 1915, p. 817) and Boruttau (_ibid._, July 29, 1915, p. 924) and
of Hawk and his associates. There is no reason to assume that weight
gained under its use would be more readily lost than weight gained
from any other food. However, in view of its laxative action, the
average individual can ingest only from 1 to 2 gm. of nitrogen a day in
this form. This obviously greatly limits its value as a food. Owing to
its high nuclein content, it is contraindicated in gout.
As a source of water soluble growth promoting as well as antineuritic
vitamin, yeast has become thoroughly established as the result of
the recent works of numerous investigators. However, as such common
foods as milk, rice, wheat, oats and beans also contain such vitamin,
there is little likelihood of its proving of therapeutic value on that
account. In other words, yeast and other vitamin containing foods have
specific growth promoting qualities only when the stunting is due to
lack of vitamin. A minute amount of this substance suffices to produce
maximal results. More is of no use. Hess (_Proc. Soc. Exper. Biol. &
Med._ =13=:145, 1916) found yeast of no value in infantile scurvy.
The most important question in connection with yeast therapy is to what
extent it is endowed with “antibiotic” power, that is, to what degree
it is capable of inhibiting the growth of other organisms. That this
frequently occurs in cultures in vitro is shown by the fact that yeast
contamination may practically eradicate the growth of certain other
organisms. That, on the other hand, this is not true for all forms of
bacterial life is shown by the fact that there is definite symbiosis
between yeast and lactic acid bacilli (Northrup: _Soc. Tech. Bull._ 15,
Mich. Agr. Expa. Sta., 1912).
That its “antiseptic power is, on the whole insignificant” has
been shown by Palier (_Diet. & Hyg. Gaz._, March, 1906), who found
commercial yeasts commonly contaminated with numerous bacteria, the
most frequent being _Bacillus coli-communis_ or one of its congeners.
An antagonistic action by yeast is claimed against _Staphylococcus
pyogenes_, and on the strength of this, Buchholtz (Ueber Acne und eine
neue erfolgreiche Behandlung derselben, _Berl. klin. Wchnschr._, Feb.
2, 1914, p. 215) employed it locally in the treatment of acne and
obtained a positive but temporary effect. He believes that the effect
is improved by the combination of yeast with an equal quantity of boric
acid. He employed this as a dusting powder applied freely to the skin
once daily, after the application of a thin layer of a boric acid salve
(boric acid powder from 40 to 50, glycerin and water, of each 100) to
make it stick better. In cases in which the nose was markedly involved,
he also used this as a snuff. Yeast poultices have been employed with
asserted great benefit in the treatment of wound infection of all kinds
(Kempf, E. J.: _Ind. M. J._, September, 1904, p. 97).
The use in leukorrhea was recommended by Hippocrates Abraham (_Mon.
Geb. Sym._, 1910) and many others report favorable results from yeast
in the treatment of gonorrheal vaginitis. In various gastro-intestinal
infections, yeast has been lauded by many, among others, Thiercelin and
Chevrey. It has been given by mouth, but most especially in high rectal
enemas.
Still more from a theoretical standpoint is the reassertion of the
curative value of the oral administration of yeast in various cutaneous
disorders. Thus Hawk and his collaborators report cure or improvement
in all of seventeen cases of acne vulgaris and eight cases of acne
rosacea. They also report seventeen cases of furunculosis, in all but
one of which there was cure or improvement from yeast treatment. They
are unable to decide whether the result is due to the laxative action,
the production of leukocytosis, or to other influences.
Yeast is probably best taken incorporated in food. Hawk and his
associates found that yeast may well be incorporated in wheat biscuits,
and that in this way a yeast-wheat combination of most agreeable flavor
was produced: that, in fact, the biscuits with the yeast tasted better
than those without it. They found by tests that in bread making as
much as 20 per cent. of the flour might be replaced by dry yeast, and
that thereby a loaf would be produced that was excellent in every
way and possessed of an attractive flavor. The dry yeast was prepared
by desiccating compressed yeast at 105 C. in a current of air, and
then milling it to produce a flour of the approximate fineness of
ordinary wheat flour. They also found that yeast may be added to meat
preparations, such as Hamburger steak, to the extent of 2.5 per cent.,
yielding a preparation of very satisfactory taste.--(_Query in The
Journal A. M. A., Aug. 23, 1919._)
BRIEFER PARAGRAPHS
Laxol and Lysol--The Short and Catchy Proprietary Name
A laborer went to a Brooklyn physician for treatment and was given
three prescriptions. One of the prescriptions, according to the _Food
and Drug Bulletin_ of the Department of Health, City of New York,
called for “Laxol,” the word being written on a piece of blank paper
without directions. The drug clerk misread the prescription and
dispensed an “original” bottle of “Lysol” which bore the usual poison
label with skull and cross bones. The man drank the entire 3 ounces
of Lysol and died half an hour later. The case is now in the hands of
the District Attorney, the drug clerk being held under $10,000 bail.
“Laxol,” as our readers know, is castor oil sweetened with saccharin
and flavored with peppermint. There is no excuse for prescribing the
product. The official Aromatic Castor Oil (Ol. Ricin. Arom.) of the
National Formulary would answer every purpose served by the proprietary
preparation.--(_Editorial from The Journal A. M. A., May 29, 1920._)
Look Up Its Rating
Modern business has become so complex that it is no longer possible for
those engaged in trade to know, offhand, the financial responsibility
of their prospective customers. The commercial agency is a natural
development; it aims to supply the technical (financial) information
which the conservative business man needs but is otherwise unable
to get. When John Doe & Co. contemplates entering into business
arrangements with Henry Roe & Son to a degree that involves financial
obligations, it looks up Roe in the rating book of Dun or Bradstreet
and probably calls for a special commercial report on the concern.
These facts are so elemental and obvious as to be trite. The complexity
of modern medicine, especially in the pharmacologic field, has made it
a physical impossibility for physicians to know the scientific status
of scores of pharmaceutical products put out under proprietary or
brand names. It was recognition of this fact that brought about the
creation by the American Medical Association of the Council on Pharmacy
and Chemistry. This body of experts, serving without remuneration and
reporting without fear or favor on the newcomers to the pharmaceutical
world, places at the disposal of physicians unbiased information, free
alike from prejudice or prepossession. As the commercial agency reports
on the commercial probity of individuals and firms, so the Council on
Pharmacy and Chemistry reports on what might be called the scientific
probity of proprietary and unofficial pharmaceutical products. The
commercial agency issues, at no small expense to its customers, rating
books; the council on Pharmacy and Chemistry issues, at a nominal
price, “New and Nonofficial Remedies.” The commercial agency, for a
substantial fee, will furnish reports on business concerns; the Council
on Pharmacy and Chemistry will, without any expense to the profession,
furnish reports on proprietary products used for the relief or cure of
human ailments. The careful business man avails himself of the services
of the commercial agency; there are financial interests at stake. The
conscientious physician will avail himself of the services of the
Council; there are, it may well be, lives at stake.--(_Editorial from
The Journal A. M. A., April 24, 1920._)
The Medical Profession and Commercial Interests
Last week The Journal published a letter received by a physician in
Milwaukee from a firm of lawyers representing the Farbwerke-Hoechst
Company. In this communication the physician was threatened with suit
if he published further unfavorable reports regarding that firm’s
preparation. Quoting from the attorney’s letter:
“Mr. Metz directs us to inform you that the publication of this
article and the statements therein were seriously damaging to the
Farbwerke-Hoechst Company, and directs us to say further to you
that he and the corporation will hold you personally responsible
for any repetition, oral or written, of the same or of similar
statements to the same effect.”
We were under the impression that the time had passed when a
proprietary medicine manufacturer would presume to threaten a physician
for making an honest report of his results with any therapeutic
agent. Such condition did exist once, before the Council on Pharmacy
and Chemistry undertook its work. Now comes Mr. Metz to revive this
relic of an historic but infamous period in the history of American
proprietary medicine manufacturing. Even Mr. Vanderbilt regretted that
he ever said “The public be d----.” One of the elementary principles
in the practice of medicine is that the individual physician shall let
others know his results, whether good or bad, in any line of treatment.
It is by such interchange of knowledge and experience that progress in
medicine is possible. Yet Mr. Metz would interfere with the diffusion
of such knowledge and experience when it applies to proprietary
medicines. His legal threat against Dr. Sargent is “terrorism” applied
to the medical profession.--(_Editorial from The Journal A. M. A., June
8, 1918._)
Rabbit-Foot Therapy
Few but ignorant darkies have any great faith in the therapeutic
efficacy of the left hind foot of a rabbit caught in the churchyard
in the dark of the moon. In the light of modern therapeutics one is
tempted to believe, however, that had some one person or firm an
exclusive proprietary right to this particular brand of rabbits’
feet, there would be many intelligent people--and not all of them
laymen--ready to swear by rabbits’ foot therapy. In medical journals
(whose advertising pages set forth the virtues of the pedal extremities
of _Lepus sylvaticus_) many solemnly scientific articles would probably
appear relating the success that the writers had had with this form
of therapy in the treatment of some distressing stubborn conditions
that had failed to respond to all previous efforts. Is it ubiquity
that has saved the homely cotton-tail from being a therapeutic
hero?--(_Editorial from The Journal A. M. A., Sept. 29, 1917._)
Secret Remedies and the Principles of Ethics
Many hundreds, possibly thousands, of inquiries are received each
year by The Journal from physicians asking for information on, or
an opinion of certain proprietary remedies. In many instances the
preparations in question are essentially secret in composition,
although advertised to the profession under a fair-seeming exterior of
apparent frankness. There are on the market today--and used by members
of the American Medical Association--dozens, yes scores, of widely
advertised proprietaries that are, to all intents and purposes, secret.
The physicians who prescribe them do not know and cannot know what they
are giving their patients. On this point Section 6 of Chapter II of the
Principles of Medical Ethics of the American Medical Association says:
“... it is ... unethical to prescribe or dispense secret medicines
or other secret remedial agents, or manufacture or promote their
use in any way.”
The inherent and basic reasonableness of the various requirements of
the Principles of Medical Ethics needs no exposition or defense. A
large number of proprietary remedies which at present degrade medicine
would be wiped out of existence or, at any rate, go over to the “patent
medicine” class, where they belong, if physicians would live up to
Section 6, Chapter II, of the Principles.--(_Editorial from The Journal
A. M. A., Sept. 27, 1919._)
“Sterling Violet Ray Generator”
_To the Editor_:--I am curious to learn the value of the violet
ray in the treatment of disease. The violet ray seems to be much
in evidence in Canada at the present time in various towns. It is
well advertised, not in the same way as a “patent medicine” would
be, but as a genuine form of treatment. The enclosed booklet gives
a brief outline of what the agents for the “Sterling Violet Ray
Generator” claim it will do. The reason I am troubling you about
the matter is that I feel if there is anything in it as is claimed,
it should be better known. It also seems that if this treatment is
not capable of doing what is claimed for it, it is a rather serious
thing for a person who may defer calling a physician.
J. A. G.
ANSWER.--The “Sterling Violet Ray Generator” is a small high frequency
apparatus with some vacuum and possibly other electrodes. There is a
violet color in these vacuum electrodes when they are energized. The
apparatus is not one for producing violet or ultraviolet rays in the
scientific meaning of those words. The apparatus certainly will not do
the things claimed for it in the booklet which includes the treatment
of practically every ailment known to mankind.--(_Correspondence in The
Journal A. M. A., April 14, 1917._)
Strontium Salicylate Not Superior to Sodium Salicylate
Sodium salicylate is a valuable drug. It is official and cheap; it
is the compound generally relied on when salicylate effects are
desired. And there is no mystery about it. With the other salicylates,
mystery begins. For this reason, such studies as that of Blankenhorn
on strontium salicylate are of special value. Blankenhorn shows that
strontium salicylate possesses no advantages over sodium salicylate,
as regards either therapeutic efficacy or freedom from undesirable
by-effects. He calls attention to the fact that “the salicyl content
of strontium salicylate is about four-fifths that of sodium salicylate
based on the amount of available anion.” The question naturally arise
whether this smaller salicylate content may not contribute to the
notion that strontium salicylate is less likely to cause salicylism.
The impression as to the greater freedom of this salt from undesirable
by-effects may have arisen in part also from the fact that the more
expensive preparations are more likely to be given in small doses
than is the cheaper sodium salicylate. As Blankenhorn suggests, when
once such a tradition gains currency, it will be “lugged along”
from one textbook to another, with little or no attempt at critical
examination.--(_Editorial from The Journal A. M. A., Jan. 29, 1916._)
Vaccine As a Prophylactic in Influenza
_To the Editor_:--I am chief surgeon for a large steel industry in
Canton, and desire to do all in my power to prevent the threatened
recurrence of influenza. What is the status of the various vaccines
as a preventive or prophylactic measure? Would you advise their use
as a preventive measure, to immunize the workers in the industries?
M.D., Canton, Ohio.
ANSWER.--The status of vaccine therapy as a prophylactic for influenza
may be ascertained from the two articles appearing in The Journal,
Aug. 9, 1919: that of E. C. Rosenow and B. F. Sturdivant entitled
“Studies in Influenza and Pneumonia: Further Results of Prophylactic
Inoculations,” and that of G. W. McCoy, director, Hygienic Laboratory,
U. S. Public Health Service, on “Status of Prophylactic Vaccination
Against Influenza.” In brief, the conclusion of Rosenow and Sturdivant
is: “It appears from all of the facts at hand that by the use of a
properly prepared vaccine it is possible to rob influenza of some of
its terrors.” On the other hand, McCoy states: “The general impression
gained from uncontrolled use of vaccines is that they are of value in
the prevention of influenza; but, in every case in which vaccines have
been tried under perfectly controlled conditions, they have failed to
influence in a definite manner either the morbidity or the mortality.”
To make a conservative statement: The use of vaccine as a prophylactic
in influenza is an experiment.--(_Query in The Journal A. M. A., Sept.
27, 1919._)
Vaccines for “Colds”
_To the Editor_:--Has there been work done of sufficient extent to
be of value in justifying use of mixed “shotgun” vaccines to abort
or immunize “common colds,” that is, rhinitis, pharyngitis, acute
bronchitis, coryza, etc.?
Charles E. Bennett, M.D., Aneta, N. D.
ANSWER.--We know of no investigation which demonstrates that the use
of the commercial mixed vaccines are of value in the prevention or
treatment of “common colds” or of similar affections. The Council on
Pharmacy and Chemistry accepts for New and Nonofficial Remedies mixed
vaccines only on condition that their usefulness has been established
by acceptable clinical evidence; so far it has not admitted any of the
“influenza” or “catarrhal” mixed vaccines.--(_Correspondence in The
Journal A. M. A., Nov. 10, 1917._)
To the Editor:--Please advise me of the latest and best vaccine for
common colds.
L. J. Smith, M.D., Wilson, N. C.
Health Officer, City and County Health Department.
ANSWER.--There is no scientific evidence that common colds can be
prevented by the use of vaccines, despite the glowing recommendations
of vaccine makers and the patter of the detail man. Colds characterized
by catarrhal inflammation of the mucous membranes of the nose and
throat are caused by various organisms, including a number of the
commoner cocci and the bacillus of Pfeiffer. They are contagious,
and spread rapidly from one person to another by the transfer of the
bacteria concerned, so that small epidemics of colds are continually
occurring in homes and communities. The organism concerned in one small
epidemic may be different from that in another, and it is impossible to
anticipate what organism is about to invade the household or community.
The inoculation of mixed vaccines in the hope of providing against
a number of possible invaders fails to produce immunity sufficient
to prevent the infection of mucous membranes. Where completely
controlled experiments have been made with large numbers of persons,
colds have occurred among the inoculated in as large proportion as
among the uninoculated. During the war, some evidence was obtained
which indicated that preventive inoculation of troops with a vaccine
containing large numbers of pneumococci reduced the incidence and
mortality of pneumonia. In the case of superficial infection of the
nasal and pharyngeal mucous membranes with diverse etiology, less can
be expected, and practical results indicate that this skepticism based
on theoretical considerations is well founded.--(_Query in The Journal
A. M. A., Nov. 13, 1920._)
INDEX AND BIBLIOGRAPHY
[See Closing Paragraph to Preface, Page IV.]
PAGE
Abbott Laboratories--
B. Coli-Combined-Bacterin, 185
Barbital, 371
Calcidin Tablets, 465
M. Catarrhalis-Combined-Bacterin, 184
Neuro-Lecithin, 53
Pertussis-Combined-Bacterin, 185
Procain-Abbott, 356
Streptococcus-Rheumaticus-Combined-Bacterin, 185, 186
Streptococcus-Viridans-Combined-Bacterin, 185, 186
Triple Arsenates with Nuclein, 256
Abrams, Albert, 472
Abrams, Albert, defense of, by Upton Sinclair, 477
Acetanilid and Sodium Bromid Tablets, 566
Acetanilid Compound, Mulford, 206
Acet-Phenetidin Compound, P.-M. Co., Tablets (Pitman-Moore Co.),
Reports Council Pharm. & Chem., 1918, p. 73.
Acetylsalicylic Acid: See also Aspirin.
Acetylsalicylic Acid, American-made, examination of, 344
Acetylsalicylic Acid (Aspirin) Monsanto, 347
Acetylsalicylic Acid, M. C. W, 347
Acetylsalicylic Acid, Millikin, 347
Acetylsalicylic Acid, not Aspirin, 480
Acetylsalicylic Acid, P. W. R, 347
Acetylsalicylic Acid, Squibb, 347
Acetylsalicylic Acid--“What’s in a Name.”, 482
Adreno-Spermin Comp., Caps, 219
Advertising by means of “original” articles in medical journals, 560
Advertising principles--lay and medical, 483
Agar-lac (E. Fougera & Co., Inc.), The Journal, Nov. 14, 1914,
p. 1777; Reports Council Pharm. & Chem., 1914, p. 124;
Propaganda, ed. 9, p. 10.
Agmel (Maguey Products Co.), The Journal, Oct. 12, 1912, p. 1392.
Akoz, lead in, 328
Akoz Medicinal Mineral Water, 328
Akoz Ointment, 328
Akoz Powder, 328
Akoz Suppositories, 328
Albolene, Liquid, 106
Albolene, Liquid (McKesson & Robbins), The Journal, July 26, 1913,
p. 296; Reports Council Pharm. & Chem., 1916, p. 65.
Alborum (The Whitehouse Chemical Co., Inc.), The Journal, Dec. 12,
1914, p. 2148; Reports Council Pharm. & Chem., 1914, p. 129.
Alcohol, Hygiene and Legislation, 495
Alcresta Dental Lotion-Lilly (Eli Lilly & Co.), The Journal,
Oct. 29, 1921, p. 1441.
Alcresta Ipecac, 153
Alcresta Ipecac (Eli Lilly & Co.), The Journal, Oct. 20, 1917,
p. 1373; Reports Council Pharm. & Chem., 1917, p. 62.
Alcresta Lotion, 465
Aletrin, The Journal, Nov. 13, 1909, p. 1655; Reports Council Pharm.
& Chem., 1909, p. 135.
Aletris Compound, Elixir (Parke, Davis & Co.; Ray Chemical Co.);
Reports Council Pharm. & Chem., 1912, p. 46.
Aletris Cordial (Rio Chemical Co.), The Journal, Oct. 17, 1914,
p. 1411; Feb. 13, 1915, p. 606; Reports Council Pharm. & Chem.,
1914, p. 99; Propaganda, ed. 9, p. 43.
Alexander, H. M., Company--
Dixon’s Tubercle Bacilli Extract and Dixon’s Suspension of Dead
Tubercle Bacilli, 158
Alfatone, 28
Alfatone (Norwich Pharmacal Company), The Journal, Aug. 7, 1915,
p. 548; Reports Council Pharm. & Chem., 1915, p. 62.
Alkaline Digestine (Parke, Davis & Co.), Reports Council Pharm.
& Chem., 1912, p. 44.
Alkalithia, 242
Alkalithia (Keasbey and Mattison Company), Reports Council Pharm.
& Chem., 1919, p. 65.
Alkalol (Alkalol Co.), The Journal, Nov. 6, 1915, p. 1665; Reports
Chem. Lab., 1915, p. 110.
Alleotone (B. F. Copeland), The Journal, Feb. 1, 1908, p. 379;
Propaganda, ed. 9, p. 264.
Allied Medical Associations of America, 486
Alphozone, 99
Alphozone (Frederick Stearns & Co.), Reports Council Pharm.
& Chem., 1916, p. 50.
Ambrine, analysis of, 332
“Ambrine” and Paraffin Films, 330
Ambrine, The Journal, April 7, 1917, p. 1057; May 19, 1917, p. 1497;
Reports Chem. Lab., 1917, p. 20.
American Animal Therapy Co, 528
American Elixir of Bitter Wine, Triner’s, 139
American-made synthetic drugs, 344, 369
American Medical Association Chemical Laboratory, foreword, 322
American Medical Association Chemical Laboratory, work of, 322
American Medical Association Council on Pharmacy and Chemistry, delays
in passing on products, 20
American Medical Association Council on Pharmacy and Chemistry,
foreword, 1
American Medical Association Council on Pharmacy and Chemistry offers
services similar to Dun and Bradstreet, 570
American Medical Association Council on Pharmacy and Chemistry,
official rules of, 3
American Medical Association Council on Pharmacy and Chemistry,
present and future, 12
American Medical Association Council on Pharmacy and Chemistry
endorsed by The Journal of the Missouri State Medical
Association, 19
American Organotherapy Company, 527
Ammonium Chloride, Troches of, druggists refuse to supply, 552
Ammonium Hypophosphite, 98
Ammonium Hypophosphite, Gardner’s Syrup of, 100
Ammonium Hypophosphite, Reports Council Pharm. & Chem., 1916, p. 51.
Ammonol, 393
Ammonol (Ammonol Chemical Co.), The Journal, June 3, 1905, p. 1791;
Feb. 2, 1918, p. 337; Reports Council Pharm. & Chem., 1905, 1908,
p. 7; Propaganda, ed. 9, p. 9.
Amolin Deodorant Powder (Amolin Chemical Co.), The Journal, Feb. 22,
1908, p. 626; Reports Chem. Lab., 1909, p. 63.
Anadol (Wheeler Chemical Works), The Journal, May 21, 1910, p. 1704;
Propaganda, ed. 9, p. 245.
Analutos and Analutos Tablets (Royal Pharmaceutical Works, Meppel,
Holland), The Journal, Feb. 20, 1915, p. 684; Reports Council Pharm.
& Chem., 1915, p. 135; Reports Chem. Lab., 1915, p. 131.
Anasarcin, 383
Anasarcin advertising, 407
Anasarcin (Anasarcin Chemical Co.), The Journal, May 4, 1907, p. 1535;
Dec. 8, 1917, p. 1992; Reports Council Pharm. & Chem., 1905-8,
p. 54; Propaganda, ed. 9, p. 11.
Anderson System for Treatment of Alcoholism (The Anderson
Laboratories), Reports Council Pharm. & Chem., 1916, p. 51.
Anedemin, 383
Anedemin (Anedemin Chemical Co.), The Journal, May 4, 1907, p. 1535;
Dec. 8, 1917, p. 1992; Reports Council Pharm. & Chem., 1905-8,
p. 54; Propaganda, ed. 9, p. 11.
Anesthesin, 276
Angier’s Emulsion (Angier Chemical Co.), The Journal, Sept. 12, 1914,
p. 962; Reports Council Pharm. & Chem., 1914, p. 48; Reports Chem.
Lab., 1914, p. 55; Propaganda, ed. 9, p. 169.
Anglo-French Drug Co., Ltd.--
Collosol Cocaine, 221
Collosol preparations, 223
Cuprase, 222
Sukro-Serum, 273
Supsalvs, 274
Anistamina (M. Olivetti), Reports Council Pharm. & Chem., 1915,
p. 162.
Antero-Pituitary Comp., Caps, 219
Antidiabeticum, Bauer (Sanin-Gesellschaft), The Journal, July 30,
1910, p. 418; Propaganda, ed. 9, p. 267.
Antidysenteric Serum (Farbwerke-Hoechst Co.), Reports Council Pharm.
& Chem., 1917, p. 146.
Antikamnia (Antikamnia Chemical Co.), The Journal, June 3, 1905,
p. 1791; Feb. 8, 1908, p. 467; Reports Council Pharm. & Chem.,
1905-8, p. 7; Reports Chem. Lab., to 1909, p. 60; Propaganda,
ed. 9, pp. 9, 268, 307.
Antikamnia and Quinin (Antikamnia Chemical Co.), The Journal, July 1,
1905, p. 55.
Anti-Malta Fever Serum (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1917, p. 136.
Antimeristem-Schmidt, 408
Antimeristem-Schmidt (Laboratorium W. Schmidt), The Journal, March 8,
1913, p. 766; Dec. 6, 1919, p. 1787.
Antiphlogistine, 409
Antiphlogistine (Denver Chemical Mfg. Co.), The Journal, June 1, 1907,
p. 1875; Feb. 23, 1918, p. 557.
Anti-Pneumococcic Oil (Eimer and Amend), The Journal, Jan. 3, 1920,
p. 46; Reports Council Pharm. & Chem., 1919, p. 52.
“Anti-Pneumococcic Oil” and the use of camphor in pneumonia, 257
Antipneumococcus Serum (Farbwerke-Hoechst Co.), Reports Council Pharm.
& Chem., 1917, p. 146.
Antiseptic Powder, Maignen (Maignen Institute), The Journal, Nov. 14,
1914, p. 1778; Reports Council Pharm. & Chem., 1914, p. 57;
Propaganda, ed. 9, p. 19.
Antiseptic Powder, Tyree’s, 462
Antiseptic Powder, Tyree’s (J. S. Tyree), The Journal, Oct. 20, 1906,
p. 1316; Aug. 24, 1912, p. 666; March 30, 1918, p. 949; Reports
Council Pharm. & Chem., 1905-8, p. 22; Propaganda, ed. 9, pp. 21,
404; May 17, 1919, p. 1482.
Antiseptic Tablets Clover (Sharp & Dohme), The Journal, Aug. 26,
1911, p. 755.
Antiseptic, Tyree’s, 401
Antistaphylococcus Serum (Burroughs Wellcome & Co.), Reports Council
Pharm. & Chem., 1917, p. 137.
Antistreptococcus Serum, Aronson’s (Schering & Glatz, Inc.), Reports
Council Pharm. & Chem., 1917, p. 146.
Antistreptococcus Serum “Hoechst” (Farbwerke-Hoechst Co.), Reports
Council Pharm. & Chem., 1917, p. 146.
Anti-Syphilitic Compound (Sweeny), 268, 330
Anti-Syphilitic Compound Sweeny (National Laboratories of Pittsburgh),
The Journal, April 3, 1920, p. 965; Reports Council Pharm. & Chem.,
1920, p. 12.
Antithermoline (G. W. Carnrick Co.), The Journal, Nov. 1, 1913,
p. 1649.
Antithyroid Preparations (Antithyroidin-Moebius and
Thyreoidectin), 202
Antithyroid Preparations, Reports Council Pharm. & Chem., 1918, p. 50.
Antithyroidin-Moebius (Merck & Co.), Reports Council Pharm. & Chem.,
1918, p. 50.
Antithyroidin-Moebius and Thyreoidectin, Antithyroid Preparations, 202
Anti-Tuberculous Lymph Compound (Sweeny), 266
Anti-Tuberculous Lymph Compound, Sweeny (National Laboratories of
Pittsburgh), The Journal, April 3, 1920, p. 965; Reports Council
Pharm. & Chem., 1920, p. 12.
Anti-Vomit Tablets, 566
Anusol Suppositories, 182
Anusol Suppositories (Schering & Glatz, Inc.), The Journal, Oct. 2,
1909, p. 1112; Oct. 11, 1913, p. 1392; Jan. 31, 1914, p. 395;
March 9, 1918, p. 719; Reports Chem. Lab., 1909, p. 32; Propaganda,
ed. 9, pp. 227, 280, 281.
Apergols (H. K. Wampole Co., Inc.), The Journal, Dec. 12, 1914,
p. 2149; Reports Council Pharm. & Chem., 1914, p. 64; Propaganda,
ed. 9, p. 26.
Aphlegmatol, 273
Aphlegmatol (G. Giambalvo & Co.), The Journal, Aug. 21, 1920, p. 556;
Reports Council Pharm. & Chem., 1920, p. 23.
Apothesine, 260
Aquazone (Oxygen Water), 290
Aquazone (Oxygen Water) (Aquazone Laboratories, Inc.), Reports Council
Pharm. & Chem., 1920, p. 50.
Arbor Vitae, Reports Council Pharm. & Chem., 1912, p. 38.
Arhovin, 243
Arhovin (Schering & Glatz, Inc.), Reports Council Pharm. & Chem.,
1919, p. 66.
Armervenol, 249
Armervenol (Hille Laboratories), Reports Council Pharm. & Chem.,
1919, p. 82.
Armour and Company--
Duodenin, 76
Lecithol, 53
Pineal Gland Preparations, 213
Red Bone-Marrow Preparations, 213
Thymus Gland Preparations, 214
“Arrhenal”, 492
Arrhenal (E. Fougera & Co.) The Journal, Feb. 26, 1921, p. 595.
Arsenates, Triple, with Nuclein, 256
Arsenic and Mercury, Solution of, 231
Arsenic and Mercury, Solution of (New York Intravenous Laboratory),
The Journal, Aug. 2, 1919, p. 353; Reports Council Pharm. & Chem.,
1919, p. 26.
Arsenic, Iron and Phosphorus Compound, Hypodermic Solution No. 13, 275
“Arsenicals”, 491
Arsenicals, pharmacology of, 492
Arseno-Meth. Hyd.: See Arsenic and Mercury, Solution of.
“Arsenoven, S. S.”, 231
Arsenoven, S. S. (S. S. Products Co.), The Journal, Aug. 2, 1919,
p. 353; Reports Council Pharm. & Chem., 1919, p. 26.
Arsphenamin, 491, 494
Aseptikons (Chinosol Co.), The Journal, Nov. 14, 1914, p. 1778;
Reports Council Pharm. & Chem., 1914, p. 124; Propaganda,
ed. 9, p. 26.
Aseptinol, 401
Aseptinol (Aseptinol Mfg. Co.), The Journal, March 30, 1918,
p. 949.
Aspirin: See also Acetylsalicylic Acid.
Aspirin, 116, 544
Aspirin (The Bayer Co., Inc.), The Journal, Jan. 20, 1917; April 13,
1918, p. 1097; June 12, 1920, p. 1664; May 14, 1921, p. 1356;
June 11, 1921, p. 1697; Reports Council Pharm. & Chem., 1916, p. 43.
Aspirin--a common name, 484
Aspirin, Acetylsalicylic Acid not Aspirin, 480
Aspirin advertisements, 483
Aspirin Bayer, 116, 347, 480
“Aspirin Bayer” and the Sterling Products Company, 485
Aspirin, Lehn and Fink, 347
Aspirin Tablets, 566
Aspiro-Lithine (McKesson & Robbins), The Journal, May 28, 1910,
p. 1803; Propaganda, ed. 9, p. 281.
Atlanta Journal-Record of Medicine and Gray’s Glycerine Tonic, 429
Atophan, 313, 373, 419
Atophan (Phenylcinchoninic Acid, U.S.P.), Cinchophen, 373
“Auto-Hemic Serum”, 409
Auto-Hemic Serum (L. D. Rogers), The Journal, Feb. 14, 1920, p. 477.
Autolysin (Autolysin Laboratory), The Journal, July 24, 1915, p. 336;
Nov. 6, 1915, pp. 1647, 1662.
“Autolysin” advertising, 413
B. Coli-Combined-Bacterin, 185
B. Coli-Combined-Bacterin (The Abbott Laboratories), The Journal,
June 22, 1918, p. 1967; Reports Council Pharm. & Chem., 1918, p. 11.
B. Iodine, 198
B. Iodine (B. Iodine Chemical Co.), The Journal, Feb. 1, 1919, p. 365;
Reports Council Pharm. & Chem., 1918, p. 44.
B. Iodine Product, 199
B. Oleum Iodine, 198
B. Oleum Iodine (B. Iodine Chemical Co.), The Journal, Feb. 1, 1919,
p. 365; Reports Council Pharm. & Chem., 1918, p. 44.
Baby Taeniafuge-Grape (Grape Capsule Co.), Reports Council Pharm.
& Chem., 1915, p. 174.
Bacilli Emulsion, Bovine (Farbwerke-Hoechst Co.), Reports Council
Pharm. & Chem., 1917, p. 146.
Bacilli Emulsion, Koch’s (Farbwerke-Hoechst Co.), Reports Council
Pharm. & Chem., 1917, p. 146.
Bacillicide (Prophytol Products Co.), The Journal, Nov. 14, 1914,
p. 1778; Reports Council Pharm. & Chem., 1914, p. 125.
Bacillus Acidophilus Cultures, The Journal, Dec. 20, 1919, p. 1895;
Reports Council Pharm. & Chem., 1919, p. 51.
Bacillus Vaccine, Friedländer. See Friedländer Bacillus Vaccine.
Bacterial Vaccine, Special, Nos. 2, 3, 4, 5, 11, 15 and 16, 254
Bakurol (Sharp & Dohme), The Journal, July 10, 1915, p. 175.
Baldwin, Z. L., and the Allied Medical Associations of America, 490
Balsamea Co.--Syrup Leptinol (formerly Syrup Balsamea), 268
Baneberry, Reports Council Pharm. & Chem., 1912, p. 38.
Baptisin, The Journal, Nov. 13, 1909, p. 1655; Reports Council Pharm.
& Chem., 1909, p. 135.
Barbital (Abbott), 371
Barbital (Antoine Chiris), 371
Barbital (Halter), 371
Barbital (Rector Chemical Company), 371
Barbital (Veronal), 370
Barbital Sodium (Medinal or Veronal-Sodium), 371
“Basic Cancer Research”, 414
Baume Analgesique, Bengué (Thos. Leeming & Co.), The Journal, Dec. 14,
1912, p. 2173; Propaganda, ed. 9, p. 267.
Bayer Company, Inc.--
Aspirin, 116, 347, 480
Helmitol, 295
Lycetol, 214
Piperazine, 214
Bee, Honey, Reports Council Pharm. & Chem., 1912, p. 38.
Beef Extract (Swift & Co.), The Journal, Jan. 23, 1909, p. 311;
Propaganda, ed. 9, p. 471.
Beef Extract, Coin Special (G. H. Hammond & Co.), The Journal,
Jan. 23, 1909, p. 311; Propaganda, ed. 9, p. 472.
Beef Extract, Concentrated Fluid (Armour & Co.), The Journal,
Jan. 23, 1909, p. 311; Propaganda, ed. 9, p. 471.
Beef Extract, Fluid (Cibilis Co.), The Journal, Jan. 23, 1909, p. 311;
Propaganda, ed. 9, p. 472.
Beef Extract, Fluid, “Rex” (Cudahy Packing Co.), The Journal, Jan. 23,
1909, p. 311; Propaganda, ed. 9, p. 471.
Beef, Extract of, Premier (Libby, McNeil & Libby), The Journal,
Jan. 23, 1909, p. 311; Propaganda, ed. 9, p. 471.
Beef Juice, Wyeth’s (John Wyeth & Bro.), The Journal, Nov. 20, 1909,
p. 1754; Reports Council Pharm. & Chem., 1909, p. 137; Propaganda,
ed. 9, p. 123.
Beer and cancer cures, 494
Bell & Co., Inc.--Bell-Ans (Pa-Pay-Ans Bell), 380, 418
Bell-Ans (Bell & Co.), The Journal, Aug. 24, 1909, p. 569; May 9,
1914, p. 1492; Nov. 24, 1917, p. 1815; Feb. 23, 1918, p. 557;
Reports Council Pharm. & Chem., 1909, p. 108; Propaganda, ed. 9,
pp. 151, 282.
Bell-Ans (Pa-Pay-Ans Bell), 380, 418
Benetol (Northern Chemical Assn.), The Journal, April 15, 1911,
p. 1128; Reports Chem. Lab., 1911, p. 82.
Betul-ol (E. Fougera & Co., Inc.), The Journal, Dec. 12, 1914,
p. 2148; Reports Council Pharm. & Chem., 1914, p. 62; Reports Chem.
Lab., 1914, p. 74; Propaganda, ed. 9, p. 27.
Beveridge, James Wallace--Secretin-Beveridge, 170
Bile Salt and Holadin Mixtures, 207
Bile Salts, Holadin and Phenolphthalein, Capsules of, 208
Bile Salts, Succinate of Soda and Holadin, Capsules of, 208
Bile Salts, Succinate of Soda and Phenolphthalein, Capsules of, 208
Bile Salts, Succinate of Soda and Phenolphthalein, Capsules of,
Fairchild (Fairchild Bros. & Foster), Reports Council Pharm.
& Chem., 1918, p. 59.
Biniodol, 121
Biniodol (Charles C. Yarbrough), The Journal, Feb. 24, 1917, p. 650;
Reports Council Pharm. & Chem., 1917, p. 10; Reports Chem. Lab.,
1916, p. 108.
Biologic therapeutics and its commercial domination, 496
Biosol (Vito Chemical Laboratories), The Journal, March 8, 1913,
p. 767; Propaganda, ed. 9, p. 284.
Bischoff, C., & Co.--Hydragogin, 41
Bischoff, Ernst, Company, Inc.--
Digitalysatum, 63
Hydropsin, 61
Styptysate, 318
Bismon (Kalle Color and Chemical Co.), Reports Council Pharm. & Chem.,
1921, p. 12.
Bismuth and Calomel Comp. Tablets, 566
Bismuth and Iron Citrate Soluble (Wellcome Brand) (Burroughs Wellcome
& Co.), Reports Council Pharm. & Chem., 1920, p. 51.
Bismuth and Lithium Citrate Soluble (Wellcome Brand) (Burroughs
Wellcome & Co.), Reports Council Pharm. & Chem., 1920, p. 51.
Bismuth Iodo-Resorcin Sulphonate, The Journal, Feb. 11, 1911, p. 441;
Reports Chem. Lab., 1911, p. 14.
Bismuth, Opium and Phenol Tablets, The Journal, July 25, 1908, p. 330;
Dec. 17, 1910, p. 2169; May 6, 1911, p. 1344; Reports Chem. Lab., to
1909, p. 28; 1910, p. 85; 1911, p. 22.
Bismuth, Opium and Phenol Tablets (Hance Bros. & White; Wm. S. Merrell
Chemical Co.; Sharp & Dohme; F. Stearns & Co.; Truax, Greene & Co.;
H. K. Wampole & Co., Inc.; Wm. R. Warner & Co.), The Journal,
July 25, 1908, p. 330; Dec. 17, 1910, p. 2169; May 6, 1911, p. 1344;
Reports Chem. Lab., to 1909, p. 28; 1910, p. 85; 1911, p. 22.
Bismuth, Resorcinol Compound, Capsules, 157
Bismuth Resorcinol Compound, Capsules (Gross Drug Co., Inc.), Reports
Council Pharm. & Chem., 1917, p. 139.
Bismuth Tribromphenate-Merck, 216, 349
Bismuth Tribromphenate, standardization of, 348
Bismuth Tribromphenolate, report to Council of National Defense, 352
Bi-Taride Tablets (Germicidal Products Corporation), The Journal,
Sept. 16, 1916, p. 895; Reports Council Pharm. & Chem., 1916, p. 21.
Bitter Bark, Reports Council Pharm. & Chem., 1912, p. 39.
Bitter Wine, Triner’s American Elixir of, 139
Bladder Wrack, Reports Council Pharm. & Chem., 1912, p. 39.
Blandine Laxative, Mulford (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1914, p. 136.
Blaud, Arsenic and Strychnine Capsules, Frosst’s, 56
Blaud, Arsenic and Strychnine Capsules, Frosst’s (C. E. Frosst & Co.),
Reports Council Pharm. & Chem., 1915, p. 164.
Blaud Capsules, Frosst’s, 56
Blaud Capsules, Frosst’s (C. E. Frosst & Co.), Reports Council Pharm.
& Chem., 1915, p. 164.
Blaud’s Pills, The Journal, April 17, 1915, p. 1344; Reports Chem.
Lab., 1915, p. 7.
Blood Tonic, Alterative (Parke, Davis & Co.), Reports Council Pharm.
& Chem., 1912, p. 47.
Blue Cohosh, The Journal, Sept. 11, 1915, p. 972.
Borcherdt’s Malt Olive with Hypophosphites, 84
Borolyptol (Palisade Mfg. Co.), The Journal, Nov. 15, 1913, p. 1812.
Borotetramine (Takamine Laboratories), The Journal, Feb. 19, 1921,
p. 538; Reports Council Pharm. & Chem., 1921, p. 13.
Bovinine (The Bovinine Co.), The Journal, Nov. 20, 1909, p. 1754;
Reports Council Pharm. & Chem., 1909, p. 137; 1914, p. 105;
Propaganda, ed. 9, p. 123.
Breitenbach, M. J., Company--Pepto-Mangan, 387
Bristol-Myers Company--
Sal Hepatica, 451
Ziratol, 148
Brobor: See Episan.
Broeman, C. J.--Final report on Proteogens, 450
Bromide and Acetanilid Compound-Mulford, Granular Effervescent
(H. K. Mulford Co.), Reports Council Pharm. & Chem., 1918, p. 58.
Bromide, Granular Effervescent and Acetanilid Compound-Mulford, 206
Bromides, Peacock’s, 400
Bromides, Peacock’s (Peacock Chemical Co.), The Journal, April 3,
1915, p. 1177; March 2, 1918, p. 643; Reports Council Pharm.
& Chem., 1915, p. 24; Propaganda, ed. 9, p. 28.
Bromides with Cypripedium Compound (Truax, Greene & Co.), Reports
Council Pharm. & Chem., 1912, p. 43.
Bromidia, 399
Bromidia (Battle & Co.), The Journal, May 16, 1914, p. 1573; March 2,
1918, p. 642; Reports Council Pharm. & Chem., 1914, p. 15;
Propaganda, ed. 9, p. 31.
Bromin-Iodin Compound, 97
Bromin-Iodin Compound (Bromin-Iodin Chemical Co.), The Journal,
June 4, 1910, p. 1884; Dec. 23, 1916, p. 1956; Reports Council
Pharm. & Chem., 1916, p. 40; Propaganda, ed. 9, p. 285.
Brom-I-Phos, 136
Brom-I-Phos (The National Drug Co.), The Journal, June 30, 1917,
p. 2001; Reports Council Pharm. & Chem., 1917, p. 32; Reports Chem.
Lab., 1917, p. 43.
Bromo-Mangan (Reinschild Chemical Co.), Reports Council Pharm.
& Chem., 1915, p. 165.
Broom Corn, Reports Council Pharm. & Chem., 1912, p. 39.
Bruschettini Curative Vaccine: See Curative Vaccine, Bruschettini.
Buchu and Hyoscyamus Compound, Tyree’s Elixir of, 57
Buchu and Hyoscyamus Compound, Elixir of, Tyree’s (J. S. Tyree),
Reports Council Pharm. & Chem., 1915, p. 167.
Buchu and Pareira Compound, Elixir (Parke, Davis & Co.), Reports
Council Pharm. & Chem., 1912, p. 46.
Buchu, Juniper and Acetate Potassium, Elixir (Pitman-Moore Co.),
Reports Council Pharm. & Chem., 1915, p. 167.
Budwell’s Emulsion of Cod-Liver Oil, Nos. 1 and 2, 22
Burdick-Abel Laboratory--Hypodermic Solution No. 13, Iron, Arsenic
and Phosphorus Compound, 276
Burroughs Wellcome and Company--Soamin, 253
Cacodylate, Ferric, 292
Cactin, now Cactoid (The Abbott Laboratories), The Journal, Sept. 21,
1907, p. 1021; March 21, 1908, p. 956; April 4, 1908, p. 1140;
March 12, 1910, p. 888; Aug. 6, 1910, p. 455; Reports Council Pharm.
& Chem., 1910, p. 41; Propaganda, ed. 9, p. 37.
Cactina (Sultan Drug Co.), The Journal, Sept. 21, 1907, p. 1021;
March 21, 1908, p. 956; April 4, 1908, p. 1140; March 12, 1910,
p. 888; Aug. 6, 1910, p. 455; Jan. 19, 1918, p. 185; Reports Council
Pharm. & Chem., 1910, p. 41; Propaganda, ed. 9, p. 37.
Cactina Pillets, 391
Cactus Compound Pills (Heart Tonic), The Journal, April 29, 1916,
p. 1387.
Cactus Grandiflorus, The Journal, Sept. 21, 1907, p. 1021; March 12,
1910, p. 888; Jan. 7, 1911, p. 26; Reports Council Pharm. & Chem.,
1910, p. 40; Propaganda, ed. 9, p. 36.
Calcidin Abbott (The Abbott Laboratories), The Journal, Sept. 7, 1907,
p. 865; Reports Chem. Lab., to 1909, p. 7.
Calcidin Tablets (Abbott), 465
Calcidin Tablets (The Abbott Laboratories), The Journal, Sept. 25,
1920, p. 892.
Calcium Comp., Elixir Iodo-Bromide of, “Without Mercury” and “With
Mercury”, 52
Calcium Glycerophosphate and Sodium Glycerophosphate, 99
Calcium Glycerophosphate, Reports Council Pharm. & Chem., 1916, p. 52.
Calcylates Compound, Elixir, The Journal, April 22, 1916, p. 1307.
Calcylates Compound, Pulvoids, 226
Calcylates Compounds, Pulvoids (The Drug Products Co.), The Journal,
June 14, 1919, p. 1784; Reports Council Pharm. & Chem., 1919, p. 19.
Calcylates, Pulvoids, 85
Calmine (The Abbott Laboratories), The Journal, Jan. 14, 1911, p. 137;
Propaganda, ed. 9, p. 286.
Calomel and Bismuth Comp. Tablets, 566
Campetrodin and Campetrodin No. 2, 193
Campetrodin and Campetrodin No. 2 (A. H. Robins Company), The Journal,
Sept. 21, 1918, p. 993; Reports Council Pharm. & Chem., 1918, p. 27.
Camphenol (Johnson & Johnson), The Journal, Nov. 5, 1910, p. 1662;
Reports Chem. Lab., 1910, p. 112; Propaganda, ed. 9, p. 287.
Campho-Phenique, 418
Campho-Phenique (Campho-Phenique Co.), The Journal, April 20, 1907,
p. 1365; Feb. 9, 1918, p. 408; Reports Council Pharm. & Chem.,
1905-8, p. 51; Propaganda, ed. 9, p. 40.
Campho-Phenique Powder (Campho-Phenique Co.), The Journal, April 20,
1907, p. 1365; Reports Council Pharm. & Chem., 1905-8, p. 51;
Propaganda, ed. 9, p. 40.
Camphor in pneumonia, 257
Cancer cures and beer, 494
Cancer, Edward Percy Robinson’s “Cure” for (Tekarkin), 458
Cancer Remedy, Koch’s (Wm. F. Koch), The Journal, Feb. 12, 1921,
p. 466; Feb. 19, 1921, p. 537.
Cancer Remedy, William F. Koch’s, 437
Cancer Research, Basic, and Cosmopolitan Cancer Research Society, 414
Cancer Serum, Glover’s, 425
Cancer Serum, Glover’s (T. J. Glover), The Journal, Jan. 1, 1921,
p. 52; Feb. 5, 1921, p. 396.
Cannabis Compound, Syrup (Pitman-Moore Co.), Reports Council Pharm.
& Chem., 1915, p. 168.
Cano’s Methyl-Phenol Serum, 251
Cano’s Normal Phenol Serum, 251
Capell’s Uroluetic Test: See Uroluetic Test, Capell’s.
Caps. Adreno-Spermin Comp. (Henry R. Harrower), The Journal, Jan. 18,
1919, p. 213; Reports Council Pharm. & Chem., 1918, p. 42.
Caps. Antero-Pituitary Comp. (Henry R. Harrower), The Journal,
Jan. 18, 1919, p. 213; Reports Council Pharm. & Chem., 1918, p. 42.
Caps. Folio Digitalis (Upsher Smith), Reports Council Pharm. & Chem.,
1920, p. 52.
Caps. Hepato-Splenic Comp. (Henry R. Harrower), The Journal, Jan. 18,
1919, p. 213; Reports Council Pharm. & Chem., 1918, p. 42.
Caps. Pancreas Comp. (Henry R. Harrower), The Journal, Jan. 18, 1919,
p. 213; Reports Council Pharm. & Chem., 1918, p. 42.
Caps. Placento-Mammary Comp. (Henry R. Harrower), The Journal,
Jan. 18, 1919, p. 213; Reports Council Pharm. & Chem., 1918, p. 42.
Caps. Thyroid Comp. (Henry R. Harrower), The Journal, Jan. 18, 1919,
p. 213; Reports Council Pharm. & Chem., 1918, p. 42.
Caps. Thyro-Ovarian Comp. (Henry R. Harrower), The Journal, Jan. 18,
1919, p. 213; Reports Council Pharm. & Chem., 1918, p. 42.
Capsules Bismuth Resorcinol Compound, 157
Captol (Mühlens & Kropff), The Journal, Sept. 10, 1910, p. 959;
Reports Chem. Lab., 1910, p. 70.
Carminzym, 194
Carminzym (Fairchild Bros. & Foster), The Journal, Sept. 28, 1918,
p. 1081; Reports Council Pharm. & Chem., 1918, p. 28.
Carnick, G. W., Co.--
Elixir Secretogen, 75
Hormotone and Hormotone without Post-Pituitary, 234
Secretin-Beveridge, 170
Secretogen, 75, 110
Carnine (E. Fougera & Co., Inc.), The Journal, Nov. 20, 1909, p. 1754;
Reports Council Pharm. & Chem., 1909, p. 137; Propaganda, ed. 9,
p. 123.
Caroid (Mead Johnson & Co.), Reports Council Pharm. & Chem., 1914,
p. 109.
Caroid, Essence of (Mead Johnson & Co.), Reports Council Pharm.
& Chem., 1914, p. 109.
Carpanutrine (John Wyeth & Bro.), The Journal, May 11, 1907, p. 1612;
Reports Council Pharm. & Chem., 1905-8, opp. p. 64; Propaganda,
ed. 9, p. 133.
Casca-Aletris (Pullen-Richardson Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 46.
Cascara, Compound-Robins, Pil., 117
Cascara Sagrada, with Maltzyme, 211
Cascarans, Bell (Bell & Co.), The Journal, Aug. 14, 1909, p. 569;
Reports Council Pharm. & Chem., 1909, p. 111; Propaganda, ed. 9,
p. 154.
Casta-Flora, 118
Castaflora (The Wm. S. Merrell Chemical Co.), The Journal, Jan. 27,
1917, p. 303; Reports Council Pharm. & Chem., 1916, p. 45.
Castrox (Purdue Newberry Co.), The Journal, Dec. 23, 1916, p. 1956;
Reports Council Pharm. & Chem., 1916, p. 41.
Catarrhal Vaccine Combined-Lilly, 187
Catarrhal Vaccine Combined-Lilly (Eli Lilly & Co.), The Journal,
June 22, 1918, p. 1967; Reports Council Pharm. & Chem., 1918, p. 11.
Caviblen (A. Grimme), Reports Council Pharm. & Chem., 1915, p. 176.
Cedron Seed, Reports Council Pharm. & Chem., 1912, p. 40.
Celerina (Rio Chemical Co.), The Journal Oct. 17, 1914, p. 1411;
Feb. 13, 1915, p. 606; Reports Council Pharm. & Chem., 1912, p. 40;
1914, p. 99; Propaganda, ed. 9, p. 43.
Celery, Reports Council Pharm. & Chem., 1912, p. 40.
Celery and Guarana Compound, Elixir (Ray Chemical Co.), Reports
Council Pharm. & Chem., 1912, p. 40.
Celery and Guarana, Elixir (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 40.
Celery Compound, Elixir (Nelson, Baker & Co.), Reports Council Pharm.
& Chem., 1912, p. 40.
Celery Compound, Elixir (Ray Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 40.
Celery Compound, Elixir (Smith, Kline & French Co.), Reports Council
Pharm. & Chem., 1912, p. 40.
Celery Compound, Elixir (F. Stearns & Co.), Reports Council Pharm.
& Chem., 1912, p. 40.
Celery, Elixir Guarana and (Hance Bros. & White), Reports Council
Pharm. & Chem., 1912, p. 40.
Cellasin (Mead Johnson & Co.), The Journal, Sept. 12, 1908, p. 931;
Oct. 30, 1909, p. 1406; Reports Council Pharm. & Chem., 1905-8,
p. 198; 1909, p. 118.
Cephaelin, 203
Cephaelin, Reports Council Pharm. & Chem., 1918, p. 52.
Cerelene, 219, 337, 362
Cerelene (Holliday Laboratories), The Journal, Feb. 15, 1919, p. 513;
Reports Council Pharm. & Chem., 1918, p. 48.
Chapoteaut’s Wine: See Wine, Chapoteaut’s.
Chemical Laboratory of the American Medical Association: See American
Medical Association.
Chemotherapy and tumors, 499
Chichester, Pil. Mixed Treatment, 310
Chiodrastis (H. K. Wampole & Co., Inc.), Reports Council Pharm.
& Chem., 1912, p. 42.
Chionacea (Nelson, Baker & Co.), Reports Council Pharm. & Chem.,
1912, p. 42; The Journal, June 14, 1919, p. 1787.
Chionanthus Compound, Elixir (Ray Chemical Co.), Reports Council
Pharm. & Chem., 1912, p. 42.
Chionanthus (Special), Elixir (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 42.
Chionia (Peacock Chemical Co.), The Journal, April 3, 1915, p. 1177;
Reports Council Pharm. & Chem., 1912, p. 42; 1915, p. 24;
Propaganda, ed. 9, p. 28.
Chlorax, 244, 246
Chlorax (Chlorine Products Company, Inc.), Reports Council Pharm.
& Chem., 1919, p. 70.
Chlorides, Platt’s, 263
Chlorinated Eucalyptol, compared with Chlorlyptus, 281
“Chlorinated Soda” Solutions, deterioration of, 358
Chlorine Products Company, Inc.--Chloron, Chlorax and Number “3”, 244
Chlorlyptus, 277
Chlorlyptus (Weeks Chemical Co.), The Journal, Nov. 27, 1920, p. 1512;
Reports Chem. Lab., 1920, p. 75; Reports Council Pharm. & Chem.,
1920, p. 28.
Chlorlyptus, comparison of, with chlorinated eucalyptol, 281
Chlorlyptus, persistence of acid reaction of, in body, 283
Chlorlyptus, report of Dr. D. Rivas on, 286
Chlorlyptus toxicity experiments, 285
Chloron, 245
Chloron (Chlorine Products Company, Inc.), Reports Council Pharm.
& Chem., 1919. p. 70.
Chologen (Leonard A. Seltzer), The Journal, Feb. 1, 1913, p. 383;
Propaganda, ed. 9, p. 288.
Chologestin (F. H. Strong Co.), The Journal, Dec. 11, 1915, p. 2108.
Chromiac Tablets (Maltbie Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 44.
Ciba Company--
Coagulen-Ciba, 290
Digiolin-Ciba, 298
“Cinchophen:” formerly “Atophan”, 419
Cinchophen (Phenylcinchoninic Acid, U. S. P.; Atophan), 373, 419
Cineraria Maritima, The Journal, Nov. 11, 1911, p. 1630; Reports
Council Pharm. & Chem., 1911, p. 48; Propaganda, ed. 9, p. 49.
Cin-U-Form Lozenges, 237
Cin-U-Form Lozenges (McKesson and Robbins), The Journal, Oct. 4, 1919,
p. 1077; Reports Council Pharm. & Chem., 1919, p. 35.
Citarin (The Bayer Company, Inc.), The Journal, Feb. 20, 1915, p. 685;
Reports Council Pharm. & Chem., 1914, p. 135.
Citrocoli (Cellarius Co.), The Journal, Jan. 21, 1911, p. 210; Reports
Council Pharm. & Chem., 1911, p. 7; Propaganda, ed. 9, p. 85.
Cleveland Medical Journal, “drug reform” as it appears to, 513
Clover Compound, Syrup Red (Nelson, Baker & Co.), Reports Council
Pharm. & Chem., 1912, p. 40.
Coagulen-Ciba, 290
Coagulen-Ciba (Society of Chemical Industry, Basle, Switzerland),
Reports Council Pharm. & Chem., 1920, p. 53.
Cod-Liver, Extract of, Wampole’s Perfected Tasteless Preparation of
(H. K. Wampole & Co., Inc.), The Journal, April 5, 1913, p. 1093;
April 10, 1915, p. 1262; Reports Council Pharm. & Chem., 1915,
p. 140; Propaganda, ed. 9, p. 52.
Cod-Liver Oil, Budwell’s Emulsion of, Nos. 1 and 2, 22
Cod-Liver Oil, Budwell’s Emulsion of, Nos. 1 and 2 (Budwell Pharmacal
Co.), The Journal, Feb. 20, 1915, p. 684; Reports Council Pharm.
& Chem., 1915, p. 135.
Cod-Liver Oil Compound, Hagee’s Cordial of the Extract of (Katharmon
Chemical Co.), The Journal, Oct. 13, 1906, p. 1208; April 10, 1915,
p. 1262; Reports Council Pharm. & Chem., 1915, p. 138; Propaganda,
ed. 9, pp. 51, 289.
Cod-Liver Oil Compound, Waterbury’s Metabolized (Waterbury Chemical
Co.), The Journal, Oct. 9, 1909, p. 1201; Reports Council Pharm.
& Chem., 1909, p. 115; Propaganda, ed. 9, p. 291. See also Compound,
Waterbury’s.
Cod-Liver Oil, Hagee’s Cordial of, 429
Cod-Liver Oil with Maltzyme, 211
Cohosh, Blue, Reports Council Pharm. & Chem., 1912, p. 40.
Colalin, 203
Colalin (Schieffelin & Co.), Reports Council Pharm. & Chem., 1918,
p. 52.
Colchi-Methyl Capsules (H. K. Wampole & Co., Inc.), Reports Council
Pharm. & Chem., 1915, p. 169.
Colchi-Sal (E. Fougera & Co., Inc.), The Journal, March 20, 1915,
p. 1016; Reports Council Pharm. & Chem., 1915, p. 136; Propaganda,
ed. 9, p. 58.
“Colds,” Vaccines for, 573
Colloid Solution Materials for Intravenous Transfusion, Hogan’s
(E. R. Squibb & Sons), Reports Council Pharm. & Chem., 1917, p. 147.
Colloidine (Boracol Chemical Co.), The Journal, March 11, 1916,
p. 831; Reports Council Pharm. & Chem., 1916, p. 7; Reports Chem.
Lab., 1915, p. 127.
Collosol Argentum, 223, 225, 226
Collosol Arsenicum, 223, 226
Collosol Cocaine, 221, 223, 226
Collosol Cocain (Anglo-French Drug Co., Ltd.), The Journal, April 12,
1919, p. 1094; Reports Council Pharm. & Chem., 1919, p. 8.
Collosol Cuprum, 223, 226
Collosol Ferrum, 223, 226
Collosol Hydrargyrum, 223, 225, 226
Collosol Iodin, 144, 223, 224, 226
Collosol Iodine (E. Fougera & Co., Inc.), The Journal, Sept. 8, 1917,
p. 841; Reports Council Pharm. & Chem., 1917, p. 49.
Collosol Manganese, 223, 225, 421
Collosol Preparations, 223
Collosol Preparations (Collosol Argentum, Collosol Arsenicum, Collosol
Cuprum, Collosol Ferrum, Collosol Hydrargyrum, Collosol Iodin,
Collosol Manganese, Collosol Quinin, and Collosol Sulphur) (Anglo-
French Drug Co., Ltd.), The Journal, June 7, 1919, p. 1694; Reports
Council Pharm. & Chem., 1919, p. 14.
Collosol Quinin, 223, 226
“Collosols:” an uncritical English endorsement, 420
Collosol Sulphur, 223, 226
Collyrium, Wyeth (John Wyeth & Bro.), The Journal, May 17, 1913,
p. 1557; Propaganda, ed. 9, p. 292.
Compound Elixir of Phosphates and Calisaya: See Tissue Phosphates,
Wheeler’s.
Compound, Waterbury’s (Waterbury Chemical Co.), The Journal, March 20,
1915, p. 1016; Reports Council Pharm. & Chem., 1915, p. 138;
Propaganda, ed. 9, p. 57.
Concentrated Solution Sodium Hypochlorite-Mulford, 358
Condurango, Reports Council Pharm. & Chem., 1911, p. 54.
Cooperation of the Pharmaceutical Houses, Reports Council Pharm.
& Chem., 1920, p. 56.
Copper Phenolsulphonate (The Abbott Laboratories), Reports Council
Pharm. & Chem., 1916, p. 54.
Cordial of Cod Liver Oil, Hagee’s, 429
Corpora Lutea (Soluble Extract) Parke, Davis & Co, 128
Corpora Lutea (Soluble Extract) (Parke, Davis & Co.), The Journal,
April 7, 1917, p. 1056; Reports Council Pharm. & Chem., 1917, p. 20.
Corydalis Compound, Elixir (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 47.
“Cosmopolitan Cancer Research Society” and Basic Cancer Research, 414
Cotarnin Salts (Stypticin and Styptol), 240
Cotarnin Salts, Reports Council Pharm. & Chem., 1919, p. 39.
Coto, Reports Council Pharm. & Chem., 1913, p. 39.
Cotoin, Reports Council Pharm. & Chem., 1913, p. 39.
Cotton Process Ether, 421
Council on Pharmacy and Chemistry: See American Medical Association.
Cream of Mustard, 218
Cream of Mustard (The Cream of Mustard Co., South Norwalk, Conn.),
Reports Council Pharm. & Chem., 1918, p. 79.
Cream of Sulphur, O’Grady’s Medicated Mineral (John H. O’Grady,
Minneapolis), Reports Council Pharm. & Chem., 1918, p. 81.
Creo Ferrum (The Gross Drug Co., Inc.), Reports Council Pharm.
& Chem., 1921, p. 16.
Creofos, 137
Creofos (Delson Chemical Co.), The Journal, July 7, 1917, p. 58;
Reports Council Pharm. & Chem., 1917, p. 34.
Creosote-Delson, 137
Creosote-Delson (Delson Chemical Co.), The Journal, July 7, 1917,
p. 58; Reports Council Pharm. & Chem., 1917, p. 34.
Creosotonic (Scott), 192, 193
Creosotonic (Scott) (Dawson Pharmacal Co.), The Journal, Aug. 24,
1918, p. 680; Reports Council Pharm. & Chem., 1918, p. 25.
Crittenton Company, Charles N.--Hydroleine, 58
Crookes Laboratories--Collosols, 420
Croustils, Simple No. 1 (Oaten Bread) (LaPorte & Gauthier), Reports
Council Pharm. & Chem., 1921, p. 17.
Croustils, No. 2 (Dechloridised and Lactosed) (LaPorte & Gauthier),
Reports Council Pharm. & Chem., 1921, p. 17.
Croustils, No. 3 (Glutinized) (LaPorte & Gauthier), Reports Council
Pharm. & Chem., 1921, p. 17.
Cu-Co-Ba Tarrant (The Tarrant Co.), The Journal, Sept. 25, 1920,
p. 891.
Cuprase, 222
Cuprase (Anglo-French Drug Co., Ltd.), The Journal, April 12, 1919,
p. 1095; Reports Council Pharm. & Chem., 1919, p. 10.
Curare, The Journal, Jan. 15, 1910, p. 219; Reports Council Pharm.
& Chem., 1910, p. 7.
Curarin, The Journal, Jan. 15, 1910, p. 219; Reports Council Pharm.
& Chem., 1910, p. 7.
Curative Vaccine, Bruschettini, 58
Curative Vaccine, Bruschettini (A. Bruschettini), Reports Council
Pharm. & Chem., 1915, p. 176.
Cypridol Capsules (E. Fougera & Co., Inc.), The Journal, Dec. 19,
1914, p. 2247; Reports Council Pharm. & Chem., 1914, p. 77;
Propaganda, ed. 9, p. 59.
Cystogen (Cystogen Chemical Co.), The Journal, Dec. 12, 1914, p. 2148;
Reports Council Pharm. & Chem., 1914, p. 66; Propaganda, ed. 9,
p. 60.
Cystogen Aperient (Cystogen Chemical Co.), The Journal, Dec. 12, 1914,
p. 2148; Reports Council Pharm. & Chem., 1914, p. 66; Propaganda,
ed. 9, p. 60.
Cystogen Lithia (Cystogen Chemical Co.), The Journal, Dec. 12, 1914,
p. 2148; Reports Pharm. & Chem., 1914, p. 66; Propaganda, ed. 9,
p. 60.
Cysto-Sedative (Strong, Cobb & Co.), The Journal, Dec. 12, 1914,
p. 2148; Reports Council Pharm. & Chem., 1914, p. 130; Propaganda,
ed. 9, p. 61.
Daggett and Miller Company, Inc.--Hex-Iodin, 236
Damiana, Allen’s Compound Extract of (Allen-Pfeiffer Chemical Co.),
The Journal, July 19, 1913, p. 211.
Darpin (Rio Chemical Co.), The Journal, Feb. 13, 1915, p. 606; Reports
Council Pharm. & Chem., 1914, p. 99; Propaganda, ed. 9, p. 43.
Dawson Pharmacal Company--Iodonized Emulsion (Scott) and Creosotonic
(Scott), 192
Delson Chemical Co., Inc.--Creosote-Delson and Creofos, 137
Denver Chemical Mfg. Co.--Antiphlogistine, 409
De Sanctis’ Rheumatic and Gout Pills, 363
Desiccated Pineal Gland--Armour, 213
Desiccated Thymus--Armour, 213
Diabetic Biscuit (Jireh Diabetic Food Co.), The Journal, March 22,
1913, p. 922.
Diabetic Flour, Jireh (Jireh Diabetic Food Co.), The Journal,
March 22, 1913, p. 922.
Diabetic Food, Jireh (Jireh Diabetic Food Co.), The Journal, Dec. 14,
1912, p. 2174.
Dial “Ciba”, 259
Dianol I, Dianol II, and Dianol III (Kalle & Co.), Reports Council
Pharm. & Chem., 1913, p. 34; Reports Chem. Lab., 1913, p. 75.
Diarrhea Calomel Pills, 566
Diastos, Liquor (H. K. Mulford Co.), The Journal, Feb. 9, 1907,
p. 533.
Diatussin (E. Bischoff & Co.), The Journal, May 17, 1913, p. 1557;
Propaganda, ed. 9, p. 293.
Di-Crotalin (Swan-Myers Co.), The Journal, Aug. 17, 1918, p. 592.
Di-Crotalin treatment of epilepsy, 465
Diethylbarbituric Acid (Merck), 371
Digalen (Hoffmann-LaRoche Chemical Works), The Journal, Sept. 5, 1914,
p. 881; Reports Council Pharm. & Chem., 1914, p. 33; Propaganda,
ed. 9, p. 68.
Digestive Tablets, Aromatic (Fraser Tablet Co.; Wm. S. Merrill
Chemical Co.; H. K. Mulford Co.; Parke, Davis & Co.; Sharp & Dohme),
The Journal, Aug. 20, 1910, p. 710; Reports Chem. Lab., 1910, p. 67;
Propaganda, ed. 9, p. 232.
Digestive Tonic (Truax, Greene & Co.), Reports Council Pharm. & Chem.,
1912, p. 44.
Digifolin-Ciba, 298
Digifolin-Ciba (Ciba Company, Inc.), The Journal, April 2, 1921,
p. 952; Reports Council Pharm. & Chem., 1921, p. 20.
Digitalis Tablets, Westerfield’s, 215
Digitalis Tablets, Westerfield’s (Westerfield Pharmacal Co.), Reports
Council Pharm. & Chem., 1918, p. 75.
Digitalone (Parke, Davis & Co.), The Journal, June 12, 1909, p. 1938;
Dec. 7, 1912, p. 2074; Jan. 11, 1913, p. 143.
Digitalysatum, 63
Digitalysatum (E. Bischoff & Co.), The Journal, Feb. 15, 1913, p. 499;
Jan. 8, 1916, p. 135; Reports Council Pharm. & Chem., 1915, p. 93.
Dionol, 422
Dionol (Dionol Company), The Journal, Jan. 26, 1918, p. 257; Feb. 7,
1920, p. 410.
Dioradin (Dioradin Co.), The Journal, Oct. 26, 1912, p. 1556; Reports
Council Pharm. & Chem., 1912, p. 23; 1913, p. 37; Propaganda, ed. 9,
p. 73.
Dios Chemical Company--Neurosine, 404
Dioscorea Compound, Elixir (H. K. Mulford Co.; Parke, Davis & Co.;
Ray Chemical Co.; F. Stearns & Co.), Reports Council Pharm. & Chem.,
1912, p. 46.
Dioviburnia (Dios Chemical Co.), The Journal, Aug. 31, 1912, p. 735;
Jan. 9, 1915, p. 166; Reports Council Pharm. & Chem., 1912, p. 46;
1914, p. 86; Propaganda, ed. 9, pp. 139, 410.
Diphtheria Antitoxin (Farbwerke-Hoechst Co.), Reports Council Pharm.
& Chem., 1917, p. 146.
Diphtheria Antitoxin, Concentrated (National Vaccine and Antitoxin
Institute), Reports Council Pharm. & Chem., 1921, p. 23.
Diphtheria Bacillus Vaccine, Reports Council Pharm. & Chem., 1918,
p. 54.
Direct Pharmaceutical Co. and William A. Webster Co., 564
Direct Sales Company, 510
Discoveries and Discoverers, 511
Diuretin (Knoll & Co.), The Journal, April 4, 1914, p. 1108; Reports
Chem. Lab., 1914, p. 7; Propaganda, ed. 9, p. 251.
Diurol (H. K. Mulford Co.), Reports Council Pharm. & Chem., 1912,
p. 45.
Dixon’s Suspension of Dead Tubercle Bacilli, 158
Dixon’s Suspension of Dead Tubercle Bacilli, Reports Council Pharm.
& Chem., 1917, p. 140.
Dixon’s Tubercle Bacilli Extract, 158
Dixon’s Tubercle Bacilli Extract; Reports Council Pharm. & Chem.,
1917, p. 140.
Dogwood, Flowering, Reports Council Pharm. & Chem., 1912, p. 41.
Dosage, dependability of tablet dosage, 556
Dotterweich, G. J., and C. K., Officers of Direct Sales Company, 510
Drug Products Co., Inc.--
Pulvoids Calcylates, 85
Pulvoids Calcylates Compound, 226
Pulvoids Natrium Compound, 108
“Drug Reform” as it appears to the Cleveland Medical Journal, 513
Drug Therapy: the fallibility of textbooks, 515
Drugs, crucial test of therapeutic evidence, 557
Dunn, Eli H., Eli products of, 424
Duodenin, 76
Duodenin, Armour (Armour & Co.), The Journal, Aug. 14, 1915, p. 639;
Jan. 15, 1916, pp. 178, 208; Reports Council Pharm. & Chem., 1915,
pp. 96, 99, 151; 1916, p. 72.
Duotonol Tablets, 94
Duotonol Tablets (Schering & Glatz, Inc.), The Journal, Sept. 30,
1916, p. 1033; Reports Council Pharm. & Chem., 1916, p. 34.
Du Pont De Nemours, E. I. and Co., Inc.--Cotton Process Ether, 421
Dysentery Bacterin-Mulford (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1917, p. 141.
Dyspepsia Compound, Elixir (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1912, p. 44.
Dyspepsia, Elixir Atonic, Phenolated (Wm. S. Merrell Chemical Co.),
The Journal, Feb. 9, 1907, p. 533.
Echinacea, The Journal, Nov. 27, 1909, p. 1836; Reports Council Pharm.
& Chem., 1909, p. 144; Propaganda, ed. 9, p. 79.
Echitone (Strong, Cobb & Co.), The Journal, Jan. 2, 1915, p. 71;
July 17, 1920, p. 193; Reports Council Pharm. & Chem., 1914, p. 80;
Propaganda, ed. 9, p. 81.
Echthol (Battle & Co.), The Journal, March 13, 1909, p. 904; Jan. 2,
1915, p. 71; Reports Council Pharm. & Chem., 1909, p. 144; 1912,
p. 38; 1914, p. 80; Propaganda, p. 81.
Echtisia (Wm. S. Merrell Chemical Co.), The Journal, Jan. 2, 1915,
p. 71; Reports Council Pharm. & Chem., 1914, p. 80; Propaganda,
ed. 9, p. 81.
Edema Improved, Tablet (Parke, Davis & Co.), Reports Council Pharm.
& Chem., 1912, p. 41.
Edema Tablet (Parke, Davis & Co.; Smith, Kline & French Co.), Reports
Council Pharm. & Chem., 1912, p. 41.
Edgar, Thomas Webster, 515
Edgar, Thomas Webster, Journal receives a letter denouncing “Medical
Clerks” and “Biased Sceptres”, 518
Edward Percy Robinson’s “Cure” for Cancer, 458
Eimer and Amend--
“Anti-Pneumococcic Oil”, 257
Phosphorcin Compound, 94
Elarson, 248
Elarson (Winthrop Chemical Company, Inc.), Reports Council Pharm.
& Chem., 1919, p. 75.
Elder, Reports Council Pharm. & Chem., 1912, p. 41.
Electrobioscope, 472
Electrargol (E. Fougera & Co.), Reports Council Pharm. & Chem.,
1920, p. 58.
Electronic Reactions, 472
Eli products of Eli H. Dunn, 424
Eli 606 Capsules, 324, 425
Eli Vaginal Capsules, 424
Eli Vim Restorative, 424
Elixir Glycerophosphates, Nux Vomica and Damiana, 95
Elixir Glycerophosphates, Nux Vomica and Damiana (Sharp & Dohme),
The Journal, Sept. 30, 1916, p. 1034; Reports Council Pharm.
& Chem., 1916, p. 35.
Elixir Iodo-Bromide of Calcium Comp. “Without Mercury” and “With
Mercury”, 52
Elixir Lactopeptine, 43
Elixir Novo-Hexamine (Upsher Smith), Reports Council Pharm. & Chem.,
1917, p. 142; Reports Chem. Lab., 1917, p. 70.
Elixir of Bitter Wine, Triner’s American, 139
Elixir of Bitter Wine, Triner’s American (Jos. Triner), The Journal,
July 14, 1917, p. 139; Reports Council Pharm. & Chem., p. 36.
Elixir of Buchu and Hyoscyamus Compound, Tyree’s, 57
Elixir Secretogen, 75
Empyroform (Schering & Glatz, Inc.), Reports Council Pharm. & Chem.,
1918, p. 55.
Emulsio Minerolein (T. R. D. Barse Co.), Reports Council Pharm.
& Chem., 1915, p. 169.
Emulsio Phen-Oleum (T. R. D. Barse Co.), Reports Council Pharm.
& Chem., 1915, p. 169.
Endoarsan, 435
Endosal, 435
Endotin (Morgenstern & Co.), Reports Council Pharm. & Chem., 1914,
p. 136.
Enesol (E. Fougera & Co., Inc.), The Journal, July 26, 1913, p. 293.
Enteronol (Enteronol Co.), The Journal, March 21, 1908, p. 977;
Reports Chem. Lab., 1909, p. 64; Propaganda, ed. 9, p. 294.
Epilepsy, Di-Crotalin treatment, 465
Episan (Gaynor-Bagstad Co.) The Journal, Sept. 25, 1915, p. 1130;
Reports Council Pharm. & Chem., 1915, p. 164.
Epsom Salt Flavoring a “discovery”, 179
Ergoapiol (Martin H. Smith Co.), The Journal, Dec. 12, 1914, p. 2149;
Reports Council Pharm. & Chem., 1914, p. 64; Propaganda, ed. 9,
p. 82.
Ergone (Parke, Davis & Co.), The Journal, Oct. 7, 1911, p. 1211;
Oct. 14, 1911, p. 1302.
Ergotole (Sharp & Dohme), The Journal, Oct. 7, 1911, p. 1211;
Oct. 14, 1911, p. 1302.
Erling, A. E., and the Allied Medical Associations of America, 488
Erling, A. E., and the Physicians’ Drug Syndicate, 432
Erpiol, Dr. Schrader (Wm. S. Merrell Chemical Co.), The Journal,
June 3, 1911, p. 1670; Reports Council Pharm. & Chem., 1911, p. 18;
Propaganda, ed. 9, p. 83.
Eskay’s Neuro Phosphates, 146
Estivin, 466
Estivin (Schieffelin and Company), The Journal, Nov. 12, 1921,
p. 1595.
Ether, Anesthesia (Cotton Process) (Du Pont Chemical Works), The
Journal, Feb. 21, 1920, p. 544; May 22, 1920, p. 1474.
Ether, Cotton Process, 421
Ethics, secret remedies and the principles of, 571
Eucalyptol, Chlorinated, comparison of Chlorlyptus with, 281
Eucalyptus, toxicity experiments, 285
Euca-Mul (The Edward G. Bintz Co.), The Journal, Oct. 29, 1921,
p. 1438.
Eumictine, 262
Eumictine (Geo. J. Wallau, Inc.), The Journal, Feb. 21, 1920, p. 542;
Reports Council Pharm. & Chem., 1920, p. 7.
Eunatrol (C. Bischoff & Co.), The Journal, Feb. 22, 1908, p. 627.
Eupeptic Hypophosphites, 83
Eupeptic Hypophosphites (Nelson, Baker & Co.), The Journal, Sept. 2,
1916, p. 761; Reports Council Pharm. & Chem., 1916, p. 15.
Eusoma (Eusoma Pharmaceutical Co.), Reports Council Pharm. & Chem.,
1912, p. 38.
Expurgo Anti-Diabetes (Expurgo Mfg. Co.), The Journal, Jan. 24, 1914,
p. 312; Reports Chem. Lab., 1914, p. 27; Propaganda, ed. 9, p. 299.
Expurgo Lapis (Expurgo Mfg. Co.), The Journal, Nov. 8, 1913, p. 1733.
Extract of Red Bone Marrow (Armour), 213
Fairchild Bros. & Foster--
Carminzym, 194
Holadin and Bile Salt Mixtures, 207
Lecithin, 53
False Unicorn, The Journal, Nov. 27, 1909, p. 1836; Reports Council
Pharm. & Chem., 1909, p. 146; Propaganda, ed. 9, p. 84.
Farbwerke-Hoechst Co.--
Procain (Novocain), 355, 357, 375
Threatens physician with suit for publishing unfavorable report of
its product, 570, 571
Febrisol (The Tilden Co.), The Journal, June 29, 1912, p. 2043.
Febri-Tone (Arthur Peter & Co.), The Journal, Feb. 1, 1908, p. 379.
Fellows’ Syrup and other preparations of Hypophosphites, 395
Fellows’ Syrup of Hypophosphites, 82
Fermenlactyl (Anglo-American Pharmacal Co., Ltd.), The Journal,
Jan. 30, 1909, pp. 372, 397.
Ferric Arsenite, Soluble, Reports Council Pharm. & Chem., 1912, p. 30.
Ferric Cacodylate, 292
Ferric Cacodylate, Reports Council Pharm. & Chem., 1920, p. 62.
Ferritonic-Woods (William A. Webster Company), The Journal, Oct. 18,
1919, p. 1231.
Ferrivine, 144
Ferrivine (E. Fougera & Co., Inc.), The Journal, Sept. 8, 1917,
p. 841; Reports Council Pharm. & Chem., 1917, p. 49.
Figwort, Reports Council Pharm. & Chem., 1912, p. 42.
Filudine, 41
Filudine (Geo. J. Wallau, Inc.), The Journal, Sept. 18, 1915, p. 1045;
Reports Council Pharm. & Chem., 1915, p. 156.
Firolyptol Plain, 120
Firolyptol Plain (The Tilden Co.). The Journal, Feb. 17, 1917, p. 564;
Reports Council Pharm. & Chem., 1917, p. 8.
Firolyptol with Kreosote, 120
Firolyptol with Kreosote (The Tilden Co.), The Journal, Feb. 17, 1917,
p. 564; Reports Council Pharm. & Chem., 1917, p. 49.
Firwein, 119
Firwein (The Tilden Co.), The Journal, Feb. 17, 1917, p. 564; Reports
Council Pharm. & Chem., 1917, p. 7.
Flint, Eaton and Company--Quassia Compound Tablets, 306
Flower, A. H., and the Allied Medical Associations of America, 489
Foral, 204
Foral (Foral Products Co.), Reports Council Pharm. & Chem., 1918,
p. 55.
Formaldehyde Lozenges, 235
Formaldehyde Lozenges, The Journal, Oct. 4, 1919, p. 1077; Reports
Council Pharm. & Chem., 1919, p. 32.
Formamint, 33
Formamint (A. Wulfing & Co.), The Journal, Jan. 27, 1912, p. 295;
Feb. 24, 1912, p. 572; Aug. 28, 1915, p. 816; Reports Council Pharm.
& Chem., 1915, p. 64; Propaganda, ed. 9, p. 303.
Formic Acid, Reports Council Pharm. & Chem., 1921, p. 25.
Formicin (Kalle Color Chemical Co.), Reports Council Pharm. & Chem.,
1919, p. 76.
Formidin (Parke, Davis & Co.), The Journal, Sept. 5, 1908, p. 818;
Reports Council Pharm. & Chem., 1905-8, pp. 164, 192; 1912, p. 48.
Formitol Tablets, 236, 271
Formitol Tablets (E. L. Patch Co.), The Journal, Oct. 4, 1919,
p. 1077; June 19, 1920, p. 1730; Reports Council Pharm. & Chem.,
1919, p. 34; 1920, p. 20; Reports Chem. Lab., 1920, p. 40.
Formosol, 158
Formosol, Sunshine’s (The Formosol Chemical Co.), Reports Council
Pharm. & Chem., 1917, p. 145.
Formothalates, Tablets, 256
Formothalates, Tablets (Tailby Nason Company), Reports Council Pharm.
& Chem., 1919, p. 92.
Formurol (Cellarius Co.), The Journal, Jan. 21, 1911, p. 210; Reports
Council Pharm. & Chem., 1911, p. 7; Propaganda, ed. 9, p. 85.
Fortossan (A. Klipstein & Co.), The Journal, Jan. 30, 1915, p. 456;
Reports Council Pharm. & Chem., 1915, p. 131; Propaganda, ed. 9,
p. 178.
Fougera E., and Co., Inc.--
Collosol Iodine, 144
Dr. De Sanctis’ Rheumatic and Gout Pills, 363
Ferrivine, 144
Intramine, 144
Phosphoglycerate of Lime (Chapoteaut), 95
Freeman, Allen W., protests regarding advertising methods used by
manufacturers of Proteogens, 445, 446
French Medicinal Company, Inc.--Syphilodol, 359, 470
Friedländer Bacillus Vaccine, Reports Council Pharm. & Chem., 1919,
p. 78.
Fringe Tree, Reports Council Pharm. & Chem., 1912, p. 42.
Fritz, W. W., and the Allied Medical Associations of America, 488
Frosst’s Blaud Capsules: See Blaud Capsules.
Frutosen (The Frutosen Drug Co.), Reports Council Pharm. & Chem.,
1921, p. 26.
G. G. Phenoleum Disinfectant (G. G. Phenoleum Co., Inc.), The Journal,
Jan. 30, 1915, p. 456; Reports Council Pharm. & Chem., 1915, p. 131.
Galactagogue action of Galega and Nutrolactis, 131
Galactagogue, alleged Galactagogue effects of Nutrolactis and Goat’s
Rue not substantiated, 131
Galactagogue (Eli Lilly & Co.), Reports Council Pharm. & Chem., 1912,
p. 43.
Galega and Nutrolactis, alleged Galactagogue action of, 131
Gardner’s Syrup of Ammonium Hypophosphite, 100
Gastrogen Tablets (Bristol-Myers Co.), The Journal, Dec. 12, 1914,
p. 2149; Reports Council Pharm. & Chem., 1914, p. 131; Propaganda,
ed. 9, p. 87.
Gelesmine Hydrochlorid, Reports Council Pharm. & Chem., 1911, p. 57.
Gelseminine, Reports Council Pharm. & Chem., 1911, p. 57.
Genitone (Wm. S. Merrell Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 44.
Genoform (C. Bischoff & Co.), The Journal, Feb. 26, 1916, p. 676.
Germaseptic Lubricant “Bing” (Chas. M. Griswold, St. Petersburg,
Fla.), Reports Council Pharm. & Chem., 1918, p. 79.
Germiletum (Dios Chemical Co.), The Journal, Jan. 9, 1915, p. 165;
Reports Council Pharm & Chem., 1914, p. 86; Reports Chem. Lab.,
1910, p. 11; Propaganda, ed. 9, p. 139.
Giambalvo, G., & Co.--Aphlegmatol, 273
Ginseng, The Journal, Oct. 24, 1914, p. 1486; Reports Council Pharm.
& Chem., 1912, p. 42.
Ginseng Compound, Elixir (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1912, p. 42.
Ginseng Compound (Special), Elixir (Parke, Davis & Co.), Reports
Council Pharm. & Chem., 1912, p. 42.
Glidine (Menley & James), The Journal, June 28, 1913, p. 2037.
Globeol (Geo. J. Wallau, Inc.), The Journal, Sept. 18, 1915, p. 1046;
Reports Council Pharm. & Chem., 1915, p. 157.
Glover’s Cancer Serum, 425
Gluten Biscuit, Pure (Kellogg Food Company), Reports Council Pharm.
& Chem., 1916, pp. 56, 57.
Gluten Biscuit, 40 per cent. (Kellogg Food Company), Reports Council
Pharm. & Chem., 1916, pp. 56, 58.
Gluten Flour, 40 per cent. (Kellogg Food Company), Reports Council
Pharm. & Chem., 1916, pp. 56, 59.
Gluten Meal, Pure (Kellogg Food Company), Reports Council Pharm.
& Chem., 1916, pp. 56, 60.
Gluten Meal, 20 per cent. (Kellogg Food Company), Reports Council
Pharm. & Chem., 1916, pp. 56, 60.
Gluten Meal, 40 per cent. (Kellogg Food Company), Reports Council
Pharm. & Chem., 1916, pp. 56, 59.
Gluten products made by the Kellogg Food Company, 100
Glutol-Schleich (Schering J. Glatz, Inc.), Reports Council Pharm.
& Chem., 1915, p. 170.
Glycerinated Vaccine Virus (National Vaccine and Antitoxin Institute),
Reports Council Pharm. & Chem.. 1921, p. 23.
Glycerine Tonic, Gray’s, 24, 429
Glycerine Tonic, Gray’s (Purdue Frederick Co.), The Journal, July 10,
1915, p. 189; Reports Council Pharm. & Chem., 1915, p. 56.
Glycero-Lecithin, Pill (Westerfield Pharmacal Co.), Reports Council
Pharm. & Chem., 1915, p. 170.
Glycerole of Lecithin, 53
Glycerole of Lecithin (Fairchild Bros, and Foster), Reports Council
Pharm. & Chem., 1915, p. 122.
Glycerophosphate Comp. No. 1, Mulford, Ampuls (H. K. Mulford Co.),
Reports Council Pharm. & Chem., 1916, p. 49.
Glycerophosphate Comp, Ampuls, 1 Cc. Squibb (E. R. Squibb & Sons),
The Journal, Feb. 3, 1917; Reports Council Pharm. & Chem., 1916,
p. 48.
Glycerophosphate, Sodium, 99
Glycerophosphates, 520
Glycerophosphates, The Journal, Sept. 30, 1916, p. 1033; Reports
Council Pharm. & Chem., 1916, p. 32.
Glycerophosphate, Calcium, 99
Glycerophosphates, Elixir, Nux Vomica and Damiana, 95
Glycerophosphates, Schering’s (Tonols), 94
Glycerophosphates, therapeutic value of, 93
Glycerosal (Röhm & Haas), Reports Council Pharm. & Chem., 1918, p. 57.
Glyco-Heroin, Smith (Martin H. Smith & Co.), The Journal, June 6,
1914, p. 1826; Reports Council Pharm. & Chem., 1914, p. 29;
Propaganda, ed. 9, p. 88.
Glyco-Thymoline (Kress & Owen Co.), The Journal, March 14, 1914,
p. 868; Oct. 10, 1914, p. 1312; Sept. 16, 1916, p. 895; Reports
Council Pharm. & Chem., 1914, p. 54; Propaganda, ed. 9, p. 92.
Glyco-Thymoline and poliomyelitis, 427
Glycozone (Drevet Mfg. Co.), The Journal, June 5, 1909, p. 1851;
Reports Council Pharm. & Chem., 1909, p. 103; Propaganda, ed. 9,
p. 95.
Glykeron: cold storage testimonials, 428
Goat Lymph Treatment, 528
Goat’s Rue, claimed Galactagogue effects of, not substantiated, 131
Goat’s Rue, The Journal, May 26, 1917, p. 1570; Reports Council
Pharm. & Chem., 1912, p. 42; 1917, p. 24.
Goehring, H. M., and the Allied Medical Associations of America, 488
Goiter Serum, Mark White, 87
Goiter Serum, Mark White (Mark White Serum Laboratories), The Journal,
Sept. 23, 1916, p. 967; Reports Council Pharm. & Chem., 1916, p. 23.
Goitreine, 88
Gomenol (Charles R. Bard), The Journal, April 4, 1914, p. 1110;
Propaganda, ed. 9, p. 304.
Gonococcic Vaccine (National Vaccine and Antitoxin Institute), Reports
Council Pharm. & Chem., 1921, p. 53.
Gonococcide (Cox Chemical Co.), The Journal, Aug. 24, 1907, p. 708.
Gonococcus Bacterin, Mixed, Special Bacterial Vaccine No. 16, 254
Gonosan, 150
Gonosan (Riedel & Co., Inc.), The Journal, Oct. 13, 1917, p. 1287;
Reports Council Pharm. & Chem., 1917, p. 57.
Gossypin, The Journal, June 3, 1911, p. 1670; Reports Council Pharm.
& Chem., 1911, p. 19; Propaganda, ed. 9, p. 84.
Gout and Rheumatic Pills, Dr. De Sanctis’, 363
Granular Effervescent Bromide and Acetanilid Compound-Mulford, 206
Granular Effervescent Sodium Phosphate Compound (Squibb)
(E. R. Squibb & Sons), Reports Council Pharm. & Chem., 1920, p. 63.
Gray’s Glycerine Tonic, 24, 429
Green Bone, Russell Prepared, 134
Gross Drug Company, Inc.--Capsules Bismuth Resorcinol Compound, 157
Guiaialin (Organic Chemical Mfg. Co.), The Journal, Sept. 5, 1908,
p. 818; May 8, 1909, p. 1511; Reports Council Pharm. & Chem.,
1905-8, p. 166; 1909, p. 76.
Guaiodine, 183
Guaiodine (Intravenous Products Co.), The Journal, April 6, 1918,
p. 1026; Reports Council Pharm. & Chem., 1918, p. 9.
Gude’s Pepto-Mangan, 387
H-M-C.: See Hyoscin-Morphin-Cactin.
Hagee’s Cordial of Cod Liver Oil, 429
Hair Cap Moss, Reports Council Pharm. & Chem., 1912, p. 43.
Hanson, A. C., and the Physicians’ Drug Syndicate, 432
Harmer Laboratories Company--Mon-Arsone, 302
Harrower, Henry R.--“Pluriglandular” Mixtures: Caps. Adreno-Spermin
Comp., Caps. Antero-Pituitary Comp., Caps. Placento-Mammary Comp.,
Caps. Thyro-Ovarian Comp., Caps. Hepato-Splenic Comp., Caps.
Pancreas Comp., and Caps. Thyroid Comp, 218
Havens’ Wonderful Discovery (E. C. Havens), The Journal, March 22,
1919, p. 883; Reports Council Pharm. & Chem., 1919, p. 7.
Hay Fever Fall Pollen Extract-Mulford (H. K. Mulford Co.), Reports
Council Pharm. Chem., 1921, p. 45.
Hay Fever Spring Pollen Extract-Mulford (H. K. Mulford Co.), Reports
Council Pharm. & Chem., 1921, p. 45.
Hectine (Geo. J. Wallau, Inc.), The Journal, Aug 8, 1914, p. 502,
Propaganda, ed. 9, p. 308.
Heffner, Charles L.--Iodiphos, 249
Hélénin and Globules of “Hélénin De Korab” (De Korab Bojemski),
Reports Council Pharm. & Chem., 1919, p. 78.
Helmitol, 295
Helmitol (Winthrop Chemical Co.), The Journal, Jan. 22, 1921, p. 260;
Reports Council Pharm. & Chem., 1920, p. 49.
Helonias Compound, Cordial, Elixir (Ray Chemical Co.), Reports Council
Pharm. & Chem., 1912, p. 41.
Helonias Compound, Elixir (Hance Bros. & White; H. K. Mulford Co.;
Parke, Davis & Co.; Smith, Kline & French Co.), Reports Council
Pharm. & Chem., 1912, p. 41.
Helonias Compound, Fluidextract (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 41.
Hemaboloids (Palisade Manufacturing Co.), Reports Council Pharm.
& Chem., 1919, p. 80.
Hemaboloids Arseniated with Strychnia (The Palisade Mfg. Co.), The
Journal, Dec. 27, 1913, p. 2306.
Hemo (Thompson’s Malted Food Co.), The Journal, Oct. 24, 1914,
p. 1494; Propaganda, ed. 9, p. 319.
Hemo-Therapin, 168
Hemo-Therapin (Hemo-Therapin Laboratories), The Journal, Jan. 5, 1918,
p. 48; Reports Council Pharm. & Chem., 1917, p. 116.
Hepatico Tablets (David Laboratories, Inc.), The Journal, Oct. 20,
1917, p. 1734; Reports Council Pharm. & Chem., 1917, p. 64.
Hepato-Splenic Comp., Caps, 219
Hexa-Co-Sal-In (Hexa-Co-Sal-In Co.), The Journal, Oct. 2, 1915,
p. 1203; Reports Council Pharm. & Chem., 1915, p. 159; Reports Chem.
Lab., 1915, p. 107.
Hexalet (Riedel & Co.), Reports Council Pharm. & Chem., 1921, p. 27.
Hex-a-lith (Smith-Dorsey Co.), The Journal, Feb. 14, 1914, p. 555.
Hexamethylenamin, commercial history of, 316
Hexamethylenamin Methylencitrate: See Helmitol.
Hex-Iodin, 236
Hex-Iodin (Daggett and Miller Co., Inc.), The Journal, Oct. 4, 1919,
p. 1077; Reports Council Pharm. & Chem., 1919, p. 33.
Heyden Chemical Works--Xeroform-Heyden, 216, 349, 352
Hille Laboratories--Mervenol and Armervenol, 249
Hillside Chemical Co.--Pil. Mixed Treatment (Chichester), 310
Hogan’s Colloid Solution Materials for Intravenous Transfusion.--
See Colloid Solution Materials for Intravenous Transfusion, Hogan’s.
Holadin and Bile Salts--Fairchild, 207
Holadin and Bile Salts, Fairchild (Fairchild Bros, and Foster),
Reports Council Pharm. & Chem., 1918, p. 59.
Holadin, Bile Salts and Phenolphthalein, Capsules of, 208
Holadin, Bile Salts and Phenolphthalein, Capsules of, Fairchild
(Fairchild Bros, and Foster), Reports Council Pharm. & Chem., 1918,
p. 59.
Holadin, Succinate of Soda and Bile Salts, Capsules of, 208
Holadin, Succinate of Soda and Bile Salts, Capsules of, Fairchild
(Fairchild Bros. & Foster), Reports Council Pharm. & Chem., 1918,
p. 59.
Holliday Laboratories--Cerelene, 219, 337, 362
Holocain Hydrochlorid, 372
Hormotone, 234
Hormotone (G. W. Carnrick Co.), The Journal, Aug. 16, 1919, p. 549;
Reports Council Pharm. & Chem., 1919, p. 30.
Hormotone without Postpituitary, 235
Hormotone Without Postpituitary (G. W. Carnrick Co.), The Journal,
Aug. 16, 1919, p. 549; Reports Council Pharm. & Chem., 1919, p. 30.
Horovitz Biochemic Laboratories Co--Lipoidal Substances, 320
Horowitz-Beebe--“Autolysin”, 413
Horse Nettle, Reports Council Pharm. & Chem., 1912, p. 43.
Hughes, K. A., Company--Salicon, 453
Hyclorite, 358
Hydragogin, 41
Hydragogin (C. Bischoff & Co.), The Journal, Jan. 27, 1906, p. 288;
Sept. 4, 1915, p. 894; Reports Council Pharm. & Chem., 1915, p. 154.
Hydrangea and Lithia, Elixir (Hance Bros. & White), Reports Council
Pharm. & Chem., 1912, p. 45.
Hydrangea, Lithiated (Lambert Pharmacal Co.), Reports Council Pharm.
& Chem., 1912, p. 42.
Hydras, 96
Hydras (John Wyeth and Bro.), The Journal, Oct. 7, 1916, p. 1107;
Reports Council Pharm. & Chem., 1916, p. 36; Reports Chem. Lab.,
1916, p. 29.
Hydrastis and Cramp Bark Compound, Elixir (Parke, Davis & Co.), The
Journal, Aug. 31, 1912, p. 735; Reports Council Pharm. & Chem.,
1912, p. 44; Propaganda, ed. 9, p. 410.
Hydrastis and Viburnum Compound, Elixir of (Smith, Kline & French
Co.), The Journal, Aug., 31, 1912, p. 735; Propaganda, ed. 9,
p. 410.
Hydrocyanate of Iron, Tilden (The Tilden Co.), The Journal, June 19,
1909, p. 2008; Reports Chem. Lab., 1909, p. 27; Propaganda, ed. 9,
p. 235.
Hydroleine, 58
Hydroleine (Charles N. Crittenton Co.), Reports Council Pharm.
& Chem., 1915, p. 171.
Hydron (Wm. S. Merrell Chemical Co.), Reports Council Pharm. & Chem.,
1912, p. 44.
Hydronaphthol (Seabury & Johnson), The Journal, Sept. 3, 1910, p. 878;
Reports Chem. Lab., 1910, p. 108; Propaganda, ed. 9, p. 308.
Hydropsin, 61
Hydropsin (E. Bischoff & Co., Inc.), The Journal, Jan. 8, 1916,
p. 135; Reports Council Pharm. & Chem., 1915, p. 94.
Hydrozone (Charles Marchand), The Journal, Sept. 23, 1905, p. 936;
Propaganda, ed. 9, p. 309.
Hymosa (Walker Pharmacal Co.), The Journal, June 11, 1910, p. 1955;
Reports Chem. Lab., 1910, p. 51; Reports Council Pharm. & Chem.,
1912, p. 44; Propaganda, ed. 9, p. 238.
Hyoscin-Morphine-Cactin, now Hyoscin-Morphin-Cactoid (The Abbott
Laboratories), The Journal, Dec. 21, 1907, p. 2103.
Hyoscyamus Compound, Tyree’s Elixir of Buchu and Hyoscyamus
Compound, 57
Hyperol (Purdue Frederick Co.), The Journal, April 18, 1914, p. 1271;
Reports Council Pharm. & Chem., 1914, p. 12; Propaganda, ed. 9,
p. 100.
Hyperthermine, 331
Hyperthermine (Pasteur Chemical Co.), The Journal, May 19, 1917,
p. 1497.
Hypno-Bromic Compound, 430
Hypodermic Solution No. 13, Iron, Arsenic, and Phosphorus
Compound, 275
Hypodermic Solution No. 13, Iron, Arsenic and Phosphorus Compound
(Burdick-Abel Laboratory), The Journal, Nov. 13, 1920, p. 1358;
Reports Council Pharm. & Chem., 1920, p. 27.
Hypophosphite, The Journal, Sept. 2, 1916, p. 760; Reports Council
Pharm. & Chem., 1916, p. 11.
Hypophosphite, Ammonium, 98
Hypophosphite, Ammonium, Gardner’s Syrup of, 100
Hypophosphite Fallacy, 80
Hypophosphites, Borcherdt’s Malt Olive with, 84
Hypophosphites Comp. (Lime and Soda)--McArthur’s Syrup of, 84
Hypophosphites, Eupeptic, 83
Hypophosphites, Fellows’ Syrup and other Preparations of, 395
Hypophosphites, Fellows’ Syrup of, 82
Hypophosphites, inertness of, 397
Hypophosphites, Maltine with Olive Oil and, 84
Hypophosphites, Maltzyme with, 84
Hypophosphites of Lime and Soda, Schlotterbeck’s Solution (Liq.
Hypophosphitum, Schlotterbeck’s), 83
Hypophosphites, Preparations of, 395
Hypophosphites, Robinson’s, 83
Hypophosphites, Robinson’s (Robinson-Pettet Company), The Journal,
Sept. 2, 1916, p. 761; Reports Council Pharm. & Chem., 1916, p. 15.
Hypophosphites, Syrup, Comp. with Quinin, Strychinin and Manganese,
Syrupus Roborans, 82
Hypoquinidol (R. W. Gardner), The Journal, Jan. 10, 1914, p. 148;
Propaganda, ed. 9, p. 310.
I. G. O., 367
Ichthynate (Mallinckrodt Chemical Works), Reports Chem. Lab., 1912,
p. 110.
Ichthytar (Szel Import & Export Co.), The Journal, March 10, 1917,
p. 796; Reports Council Pharm. & Chem., 1917, p. 18.
Influenza Combined Bacterin (Special Bacterial Vaccine No. 5), 254
Influenza Mixed Vaccine-Lilly, 187
Influenza Mixed Vaccine-Lilly (Eli Lilly & Co.), The Journal, June 22,
1918, p. 1967; Reports Council Pharm. & Chem., 1918, p. 11.
Influenza Prophylactic-Lederle (Lederle Antitoxin Laboratories),
Reports Council Pharm. & Chem., 1919, p. 81.
Influenza Serobacterin Mixed-Mulford, 187
Influenza Serobacterin Mixed-Mulford (H. K. Mulford Co.), The Journal,
June 22, 1918, p. 1967; Reports Council Pharm. & Chem., 1918, p. 11.
Influenza, Serums and Vaccines, 521
Influenza, vaccine as a prophylactic in, 572
Influenza Vaccines, 520
Ingluvin (Wm. R. Warner & Co.), The Journal, July 11, 1908, p. 142;
Reports Council Pharm. & Chem., 1905-8, p. 116; Propaganda, ed. 9,
p. 101.
Innis, Speiden & Co.--Ophthalmol-Lindemann, 189
Interol (Van Horn & Sawtell), The Journal, July 10, 1915, p. 175.
Intestinal Antiseptic W-A (The Abbott Laboratories), The Journal,
Dec. 19, 1914, p. 2247; Reports Council Pharm. & Chem., 1914, p. 78;
Propaganda, ed. 9, p. 103.
Intramine, 144
Intramine (E. Fougera & Co., Inc.), The Journal, Sept. 8, 1917,
p. 841; Reports Council Pharm. & Chem., 1917, p. 49.
Intravenin P-H (Intravenin Products Co.), Reports Council Pharm.
& Chem., 1915, p. 120.
Intravenous Compound (Loffler), 430
Intravenous Compound (Loffler) (Charles Lyman Loffler), The Journal,
Nov. 12, 1921, p. 1591.
Intravenous Products Company of America--
Endoarsan, 435
Endosal, 435
Venosal, 435
Intravenous Products Company of Denver--
Guaiodine, 183
Intravenous Specialties, 435
Venarsen, 471
Venosal, 169
Intravenous Solution, Bannerman’s (William Bannerman), The Journal,
May 31, 1913, p. 1724; Jan. 2, 1915, p. 70; Reports Council Pharm.
& Chem., 1914, p. 131; Propaganda, ed. 9, p. 105.
Intravenous Solution of Hexamethylenamin, Loeser’s, 299
Intravenous Solution of Hexamethylenamin, Loeser’s (New York
Intravenous Laboratory, Inc.), The Journal, April 16, 1921, p. 1120;
Reports Council Pharm. & Chem., 1921, p. 43.
Intravenous Solution of Hexamethylenamin and Sodium Iodid,
Loeser’s, 299
Intravenous Solution of Hexamethylenamin and Sodium Iodid, Loeser’s
(New York Intravenous Laboratory, Inc.), The Journal, April 16,
1921, p. 1120; Reports Council Pharm. & Chem., 1921, p. 43.
Intravenous Solution of Sodium Iodid, Loeser’s, 299
Intravenous Solution of Mercury Bichlorid, Loeser’s, 299
Intravenous Solution of Mercury Bichlorid, Loeser’s (New York
Intravenous Laboratory, Inc.), The Journal, April 16, 1921,
p. 1120; Reports Council Pharm. & Chem., 1921, p. 43.
Intravenous Solution of Salicylate and Iodid, Loeser’s, 299
Intravenous Solution of Salicylate and Iodid, Loeser’s (New York
Intravenous Laboratory, Inc.), The Journal, April 16, 1921, p. 1120;
Reports Council Pharm. & Chem., 1921, p. 43.
Intravenous Solution of Sodium Iodid and Sodium Salicylate, Loeser’s
(New York Intravenous Laboratory, Inc.), The Journal, April 16,
1921; page 1120; Reports Council Pharm. & Chem., 1921, p. 43.
Intravenous Solution Sodium Salicylate, Loeser’s, 299
Intravenous Solutions, Loeser’s, 299
Intravenous Specialties, 435
Intravenous Therapy, 522
Iocamfen, 338
Iocamfen Ointment, 338
Iodagol, 154
Iodagol (David B. Levy, Inc.), The Journal, Nov. 17, 1917, p. 1725;
Reports Council Pharm. & Chem., 1917, pp. 65-116; Reports Chem.
Lab., 1917, p. 80.
Iodalia (Geo. J. Wallau, Inc.), The Journal, Dec. 12, 1914, p. 2149;
Reports Council Pharm. & Chem., 1914, p. 69; Reports Chem. Lab.,
1914, p. 75; Propaganda, ed. 9, p. 106.
Iodeol, 154
Iodeol (David B. Levy, Inc.), The Journal, Nov. 17, 1917, p. 1725;
Reports Council Pharm. & Chem., 1917, p. 65-116; Reports Chem.
Lab., 1917, p. 80.
Iodex, 338, 365, 436
Iodex (Menley & James), The Journal, Nov. 30, 1912, p. 1992; June 19,
1915, p. 2085; Reports Council Pharm. & Chem., 1915, p. 144; Reports
Chem. Lab., 1915, p. 89; 1919, p. 104; Propaganda, ed. 9, p. 107;
The Journal, May 3, 1919, p. 1315.
Iodex, Liquid, 365
Iodex, Liquid (Menley and James), Reports Chem. Lab., 1919, p. 104.
Iodia (Battle & Co.), The Journal, Nov. 21, 1914, p. 1871; Reports
Council Pharm. & Chem., 1914, p. 60; Reports Chem. Lab., 1914,
p. 58; Propaganda, ed. 9, p. 108.
Iodin, Burnham’s Soluble (Burnham Soluble Iodin Co.), The Journal,
March 28, 1908, p. 1055; May 15, 1915, p. 1673; Reports Council
Pharm. & Chem., 1915, p. 50; Reports Chem. Lab., to 1909, p. 30;
Propaganda, ed. 9, pp. 110, 233.
Iodin Fumes, 523
Iodin in liquid petrolatum, 367
Iodin Petrogen (John Wyeth & Bro.), The Journal, Nov. 30, 1912,
p. 1992.
Iodin, solubility of, in liquid petrolatum, 344, 367
Iodin Tablets, Burnham’s Soluble (Burnham Soluble Iodin Co.), The
Journal, March 28, 1908, p. 1055; Reports Chem. Lab., to 1909,
p. 32; Propaganda, ed. 9, p. 233.
Iodine, B. Iodine, 198
Iodine, B. Iodine Products, 199
Iodine, B. Oleum Iodine, 198
Iodine ointments, stability of, 337
Iodine Solution, National, 300
Iodinized Emulsion (Scott), 192
Iodinized Emulsion (Scott) (Dawson Pharmacal Co.), The Journal,
Aug. 24, 1918, p. 680; Reports Council Pharm. & Chem., 1918, p. 25.
Iodinized Oil, Mark White, 87
Iodinized Oil, Mark White (Mark White Laboratories), The Journal,
Sept. 23, 1916, p. 967; Reports Council Pharm. & Chem., 1916,
p. 23.
Iodinol (Toledo Pharmacal Co.), The Journal, Aug. 20, 1921, p. 637.
Iodiphos, 249
Iodiphos (Charles L. Heffner), Reports Council Pharm. & Chem., 1919,
p. 81.
Iodival (Knoll & Co.), The Journal, March 4, 1911, p. 685.
Iod-Izd-Oil, 338
Iod-Izd-Oil (Miller’s), 49
Iod-Izd-Oil (Miller’s) (Iodum Miller Co.), The Journal, Oct. 2, 1915,
p. 1202; Reports Council Pharm. & Chem., 1915, p. 76; Reports Chem.
Lab., 1915, p. 106.
Iodo-Bromide of Calcium Comp. “Without Mercury” and “With Mercury,”
Elixir, 52
Iodo-Bromide of Calcium Comp., “Without Mercury” and “With Mercury,”
Elixir (The Tilden Co.), The Journal, Nov. 6, 1915, p. 1662;
Reports Council Pharm. & Chem., 1915, p. 160.
Iodolene and solubility of iodin in liquid petrolatum, 344
Iodolene, a solution of iodin in liquid petrolatum, 159
Iodo-Mangan, 106
Iodo-Mangan (Reinschild Chemical Co.), Reports Council Pharm. & Chem.,
1916, p. 64.
Iodomuth (Organic Chemical Mfg. Co.), The Journal, Sept. 5, 1908,
p. 818; May 8, 1909, p. 1511; Reports Council Pharm. & Chem.,
1905-8, p. 166; 1909, p. 75.
Iodonucleoid (Dinet & Delfosse Pharm. Co.), The Journal, July 22,
1911, p. 309; Reports Chem. Lab., 1911, p. 92; Propaganda, ed. 9,
p. 310.
Iodotone (Eimer & Amend), The Journal, Dec. 12, 1914, p. 2149; Reports
Council Pharm. & Chem., 1914, p. 72; Propaganda, ed. 9, p. 113.
Iodovasogen (Lehn & Fink), The Journal, Feb. 13, 1909, p. 575;
Propaganda, ed. 9, p. 408.
Iodum-Miller, 49
Iodum-Miller (Iodum-Miller Co.), The Journal, Oct. 2, 1915, p. 1202;
Reports Council Pharm. & Chem., 1915, p. 76; Reports Chem. Lab.,
1915, p. 102.
Iosaline (Iosaline Co.), The Journal, March 15, 1913, p. 849; Reports
Council Pharm. & Chem., 1913, p. 13; Propaganda, ed. 9, p. 113.
Ipecac, Alcresta, 153
Iridium Medicinal (Platinum Company of America), The Journal,
April 23, 1910, p. 1389; Propaganda, ed. 9, p. 312.
Iron, Arsenic, and Phosphorus Compound, Hypodermic Solution
No. 13, 275
Iron Arsenite, 466
Iron Citrate Green, 115
Iron Citrate Green, The Journal, Jan. 13, 1917, p. 135; Reports
Council Pharm. & Chem., 1916, p. 42.
Iron Solution for Intravenous Therapy--Perkins and Ross (Perkins
& Ross), The Journal, Nov. 14, 1914, p. 1778; Reports Council Pharm.
& Chem., 1914, p. 125.
Iron Tropon (Tropon Works), The Journal, April 23, 1910, p. 1389;
Propaganda, ed. 9, p. 313.
Isopral (The Bayer Company, Inc.), The Journal, Aug. 8, 1908, p. 487;
Reports Council Pharm. & Chem., 1905-8, p. 119.
Italian Physico-Chemical Company, 524
Ittiolo (Guiseppi W. Guidi), Reports Council Pharm. & Chem., 1920,
p. 64.
Jaroma (Jaroma Co.), The Journal, Sept. 2, 1911, p. 835; Reports Chem.
Lab., 1911, p. 103.
Johnson, N. La Doit, and the Allied Medical Associations of
America, 488
Jubol, 31
Jubol (Geo. J. Wallau, Inc.), The Journal, Aug. 14, 1915, p. 639;
Reports Council Pharm. & Chem., 1915, p. 152.
Juglandin, The Journal, Nov. 13, 1909, p. 1655; Reports Council Pharm.
& Chem., 1909, p. 135.
Kal Pheno Tooth Paste (Kal Pheno Chemical Co.), Reports Council Pharm.
& Chem., 1921, p. 41.
Kal Pheno Tooth Powder (Kal Pheno Chemical Co.), Reports Council
Pharm. & Chem., 1921, p. 41.
Kalak Water, 160
Kalak Water (Kalak Water Co., Inc.), Reports Council Pharm. & Chem.,
1917, p. 148.
Katharmon, 191
Katharmon (Katharmon Chemical Co.), The Journal, Aug. 10, 1918,
p. 487; Reports Council Pharm. & Chem., 1918, p. 23.
Keasbey and Mattison Company--Alkalithia, 242
Kefilac (Kefilac Co.), The Journal, Jan. 30, 1909, pp. 372, 397.
Kellogg Food Company--Gluten products, 100
Kelpidine: See Minson’s Soluble Iodin.
Keratin, Reports Council Pharm. & Chem., 1911, p. 58.
Kinazyme (G. W. Carnrick Co.), The Journal, Nov. 1, 1913, p. 1649.
Klein, Frederick, 415
Klipstein, A., and Company, Inc.--Dial “Ciba”, 259
Koch, William F., Cancer Remedy, 437
Kola Compound, Elixir (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1912, p. 40.
Kola Compound, Elixir (Ray Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 40.
Kolynos (Kolynos Co.), The Journal, Nov. 15, 1913, p. 1812.
Kora-Konia, 92
Kora-Konia (Gerhard Mennen Chemical Co.), The Journal, Sept. 30,
1916, p. 1034; Reports Council Pharm. & Chem., 1916, p. 31;
Reports Chem. Lab., 1916, p. 26.
Koyol (The Koyol Co.), Reports Council Pharm. & Chem., 1815, p. 172.
Kress & Owen Company--Glyco-Thymoline, 427
Kutnow’s Powder (Kutnow Bros.), The Journal, Nov. 9, 1907, p. 1619;
Propaganda, ed. 9, p. 314.
K-Y Lubricating Jelly, 147, 466
K-Y Lubricating Jelly (Van Horn & Sawtell), The Journal, May 12, 1917,
p. 1430; Sept. 29, p. 1102; Reports Council Pharm. & Chem., 1917,
p. 53.
Labordine (Labordine Pharmacal Co.), The Journal, March 30, 1907,
p. 1121; Reports Council Pharm. & Chem., 1905-8, p. 45; 1912, p. 40;
Propaganda, ed. 9, p. 115.
Lackenbach, F. I.--
Special Bacterial Vaccine, Nos. 2, 3, 4, 5, 11, 15, 16, 254
Lacteol (Dr. Boucar, Paris), The Journal, Dec. 21, 1916, p. 1959.
Lactobacilline (The Franco-American Ferment Co.), The Journal,
April 17, 1915, p. 1346; Sept. 18, 1915, p. 1049; Reports Council
Pharm. & Chem., 1915, p. 143; Propaganda, ed. 9, p. 120.
Lactone (Parke, Davis & Co.), The Journal, Jan. 30, 1909,
pp. 372, 397.
Lactopeptine (New York Pharmacal Association), The Journal, March 16,
1907, p. 959; Aug. 2, 1913, p. 358; Oct. 23, 1915, pp. 1466, 1467,
1477; Reports Council Pharm. & Chem., 1905-8, p. 43; 1913, p. 21;
1915, p. 79; Propaganda, ed. 9, p. 121.
Lactopeptine and Elixir Lactopeptine, 43
Lactopeptine, Elixir (New York Pharmacal Association), The Journal,
Feb. 9, 1907, p. 533; Oct. 23, 1915, pp. 1466, 1467, 1477; Reports
Council Pharm. & Chem., 1915, p. 79.
Lactucarium, Aubergier’s Syrup of (E. Fougera & Co., Inc.), The
Journal, Nov. 9, 1912, p. 1732; Feb. 15, 1913, p. 538;
Propaganda, ed. 9, p. 399.
Lambdin’s I. G. O., 367
Lambert, Alexander--protest regarding Pineoleum advertising
methods, 443
Lanphear, Emory--and the Medical Society of the United States, 531
Lavoris, 237
Lavoris (Lavoris Chemical Company), The Journal, Nov. 1, 1919,
p. 1380; Reports Council Pharm. & Chem., 1919, p. 35.
Laxaphen (Parke, Davis & Co.), The Journal, April 30, 1910, p. 1458,
Propaganda, ed. 9, p. 344.
Laxine (Columbus Pharmacal Co.), The Journal, April 30, 1910, p. 1458;
Propaganda, ed. 9, p. 344.
Laxol and Lysol, the short and catchy proprietary name, 570
Laxothalen Tablets (Pitman-Moore Co.), The Journal, April 30, 1910,
p. 1458; Propaganda, ed. 9, p. 344.
Lecibrin, 53
Lecibrin (Fairchild Bros. and Foster), Reports Council Pharm. & Chem.,
1915, p. 122.
Lecithin, Glycerole of, 53
Lecithin Preparations, 53, 54
Lecithin, Reports Council Pharm. & Chem., 1915, p. 122.
Lecithin Solution, 53
Lecithin Solution (Fairchild Bros. & Foster), Reports Council Pharm.
& Chem., 1915, p. 122.
Lecithine, Gare’s Granular (Gare Pharmacal Co.), Reports Council
Pharm. & Chem., 1916, p. 56.
Lecithol, 53
Lecithol (Armour & Co.), Reports Council Pharm. & Chem., 1915, p. 122.
Leeming, Thos., and Co--Trimethol, 140
Lehn and Fink--Aspirin, 347
Leptinol, Syrup (formerly Syrup Balsamea), 268
Lettuce Calmative (Nelson, Baker & Co.), Reports Council Pharm.
& Chem., 1912, p. 43.
Lettuce, Wild, Reports Council Pharm. & Chem., 1912, p. 43.
Leucocytic Extract, Archibald’s (The Western Laboratories), Reports
Council Pharm. & Chem., 1916, p. 65.
Levy, David B., Inc.--Iodeol and Iodagol, 154
Libby’s Alcresta Lotion, 465
Libradol, 293
Libradol (Lloyd Bros.), Reports Council Pharm. & Chem., 190, p. 65.
Lilly, Eli, and Co.--
Alcresta Ipecac, 153
Catarrhal Vaccine Combined-Lilly, 187
Cephaelin, 203
Influenza Mixed Vaccine-Lilly, 187
Oxyl-Iodide, 304
Rheumalgine, 23
Syrup Cephaelin-Lilly, 203
Syrup Emetic-Lilly, 203
Linder, C. O., and the Allied Medical Associations of America, 489
Lipoidal Substances (Horovitz), 320
Liquid Albolene, 106
Liquid Iodex, 365
Liquid Peptone (Eli Lilly & Co.; Stevenson & Jester Co.), The Journal,
May 11, 1907, p. 1612; Reports Council Pharm. & Chem., 1905-8,
opp. p. 64; Propaganda, ed. 9, p. 133.
Liquid Peptones with Creosote (Eli Lilly & Co.), The Journal, May 11,
1907, p. 1612; Reports Council Pharm. & Chem., 1905-8, opp. p. 64;
Propaganda, ed. 9, p. 133.
Liquid Petrolatum, 526
Liquid Petrolatum, Iodolene and the solubility of Iodin in, 344
Liquid Petrolatum, proprietary names for, 55
Liquor Santaiva, S. & D., 211
Liquor Santaiva, S. & D. (Sharp & Dohme), Reports Council Pharm.
& Chem., 1918, p. 66.
Lithia and Hydrangea, Elixir (Parke, Davis & Co.; Ray Chemical Co.;
Smith, Kline & French Co.), Reports Council Pharm. & Chem., 1912,
p. 45.
Lithiated Sorghum Compound (Sharp & Dohme), Reports Council Pharm.
& Chem., 1912, p. 39.
Liver Leaf, Reports Council Pharm. & Chem., 1912, p. 48.
Lloyd Bros.--Libradol, 293
L. O. Compound No. 1 and L. O. Compound No. 2, Tri-Arsenole, 163
L. O. Compound No. 1 and No. 2 (Medical Supply Co.), Reports Council
Pharm. & Chem., 1917, p. 156.
Loeser’s Intravenous Solutions, 299
Loeser’s Intravenous Solution of Hexamethylenamin, 299
Loeser’s Intravenous Solution of Mercury Bichloride, 299
Loeser’s Intravenous Solution of Salicylate and Iodid, 299
Loeser’s Intravenous Solution of Sodium Iodid, 299
Loeser’s Intravenous Solution of Sodium Salicylate, 299
Loffler’s Intravenous Compound, 430
Lowenthal Postgraduate Course, 527
Lubricating Jelly, K-Y, 147, 466
Lucas Laboratories’ Products, 440
Lucas Laboratories’ Products (Lucas Laboratories, Inc.), The Journal,
Sept. 20, 1919, p. 927.
Luvein Arsans, Nos. 1, 2 and 3, 441
Luvein Arsans (Plain), 440
Luvein Arsans (Plain) (Lucas Laboratories, Inc.), The Journal,
Sept. 20, 1919, p. 927.
Luvein Arsans, Nos. 1, 2 and 3 (Lucas Laboratories, Inc.), The
Journal, Sept. 20, 1919, p. 927.
Luvein Creosophite, 441
Luvein Creosophite (Lucas Laboratories, Inc.), The Journal,
Sept. 20, 1919, p. 927.
Luvein Hexacol, 411
Luvein Hexacol (Lucas Laboratories, Inc.), The Journal, Sept. 20,
1919, p. 927.
Luytie’s Homeopathic Pharmacy--Succus Cineraria Maritima, 455
Lycetol, 214
Lycetol (The Bayer Co., Inc.), Reports Council Pharm. & Chem., 1918,
p. 70.
Lymph Compound R-H (New Animal Therapy Co.), The Journal, Dec. 14,
1912, p. 2176; Propaganda, ed. 9, p. 317.
Lymphoid Compound (Lowenthal), 528
Lysoform (Lysoform Gesellschaft), The Journal, Nov. 21, 1914, p. 1870;
Reports Council Pharm. & Chem., 1914, p. 126.
Lysoform, Crude (Lysoform Gesellschaft), The Journal, Nov. 21, 1914,
p. 1870; Reports Council Pharm. & Chem., 1914, p. 126.
Lysol (Lehn & Fink), The Journal, Dec. 14, 1912, p. 2173; Reports
Council Pharm. & Chem., 1912, p. 53; Propaganda, ed. 9, p. 318.
Lysol and Laxol--the short and catchy proprietary name, 570
McArthur’s Syrup of Hypophosphites Comp. (Lime and Soda), 84
McKesson and Robbins--
Cin-U-Form Lozenges, 237
Liquid Albolene, 106
Maizavena (Wm. S. Merrell Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 44.
Maizo-Lithium (Henry Pharmacal Co.), The Journal, Feb. 6, 1915,
p. 528; Reports Council Pharm. & Chem., 1915, p. 9; Reports Chem.
Lab., 1914, p. 65; Propaganda, ed. 9, p. 198.
Malt Extract with Alteratives, Borcherdt’s (Borcherdt Malt Extract
Co.), Reports Council Pharm. & Chem., 1918, p. 51.
Malt Extract with Pepsin and Pancreatin (Wm. S. Merrell Chemical Co.;
Parke, Davis & Co.), The Journal, Feb. 9, 1907, p. 533.
Malt Extract with Yerba Santa, Borcherdt’s (Borcherdt Malt Extract
Co.), Reports Council Pharm. & Chem., 1917, p. 138.
Malt Olive, Borcherdt’s, with Hypophosphites, 84
Malt Peptonates with Arsenic, Borcherdt’s (Borcherdt Malt Extract
Co.), Reports Council Pharm. & Chem., 1917, p. 138.
Malt-Diastase Company--Maltzyme with Hypophosphites, 84
Maltine with Olive Oil and Hypophosphites, 84
Maltzyme, 211
Maltzyme (Maltzyme Company), Reports Council Pharm. & Chem., 1918,
p. 67.
Maltzyme Ferrated, 211
Maltzyme Ferrated (Maltzyme Company), Reports Council Pharm. & Chem.,
1918, p. 67.
Maltzyme with Cascara Sagrada, 211
Maltzyme with Cascara Sagrada (Maltzyme Company), Reports Council
Pharm. & Chem., 1918, p. 67.
Maltzyme with Cod Liver Oil, 211
Maltzyme with Cod Liver Oil (Maltzyme Company), Reports Council Pharm.
& Chem., 1918, p. 67.
Maltzyme with Hypophosphites, 84
Maltzyme with Yerba Santa, 211
Maltzyme with Yerba Santa (Maltzyme Company), Reports Council Pharm.
& Chem., 1918, p. 67.
Mammary Gland, Reports Council Pharm. & Chem., 1921, p. 44.
Manaca, Reports Council Pharm. & Chem., 1912, p. 43.
Manaca and Salicylates Compound, Elixir (Hance Bros. & White; Wm. S.
Merrell Chemical Co.; H. K. Mulford Co.; Nelson, Baker & Co.; Parke,
Davis & Co.; Ray Chemical Co.; Smith, Kline & French Co.; Sharp
& Dohme; F. Stearns & Co.; Truax, Greene & Co.), Reports Council
Pharm. & Chem., 1912, p. 44.
Manaca and Salicylates Compound, Elixir (Sharp & Dohme), Reports
Council Pharm. & Chem., 1912, p. 44.
Manacaline (Pullen-Richardson Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 44.
Manola (Manola Co.), The Journal, April 2, 1910, p. 1154; Reports
Chem. Lab., 1910, p. 105; Propaganda, ed. 9, p. 323.
Marienbad Tablets (J. Sicke), The Journal, July 18, 1908, p. 237.
Mark White Goiter Serum, 87
Mark White Iodinized Oil, 87
Meat Extract, “Rex” Brand (Cudahy Packing Co.), The Journal, Jan. 23,
1909, p. 311; Propaganda, ed. 9, p. 472.
Meat Juice, Valentine’s (Valentine’s Meat Juice Co.), The Journal,
Nov. 20, 1909, p. 1754; May 2, 1914, p. 1419; Reports Council Pharm.
& Chem., 1909, p. 137; 1914, p. 14; Propaganda, ed. 9, pp. 123,
129, 472.
Medeol Suppositories, 181
Medeol Suppositories (Medeol Company, Inc.), The Journal, March 9,
1918, p. 719; Reports Council Pharm. & Chem., 1918, p. 7.
Medical Society of the United States, 531
Medical Supply Company--Tri-Arsenole, L. O. Compound No. 1 and L. O.
Compound No. 2, 163
Medinal, 239, 371
Med-O-Lin (Waverly Oil Works Co.), The Journal, July 10, 1915, p. 175;
Reports Council Pharm. & Chem., 1915, p. 172.
Mellier Drug Company--
Ponca Compound, 26
Tongaline, 26
Tongaline Tablets, 27
Meningococcus Serum “Hoechst” (Farbwerke-Hoechst Co.), Reports Council
Pharm. & Chem., 1917, p. 146.
Menley and James, Ltd.--Iodex and Liquid Iodex, 365, 436
Mennen, House of--Kora-Konia, 92
Merck and Company--
Antithyroidin-Moebius, 202
Barbital-Sodium (Medinal or Veronal-Sodium), 371
Bismuth Tribromphenate, 216, 349, 352
Diethylbarbituric Acid, 371
Mercol, Howell’s (H. B. Howell & Co., Ltd.), The Journal, Jan. 16,
1909, p. 225; May 15, 1909, p. 1595; Propaganda, ed. 9, p. 326.
Mercuric Iodid, Red, (Mercury Biniodid) comparative symptoms resulting
from use of several oily suspensions of, 123
Mercury Biniodid, comparative symptoms resulting from use of several
oily suspensions of red mercuric iodid, 123
Mercury Sozoiodolate, The Journal, Feb. 13, 1909, p. 573; Reports
Chem. Lab., 1909, p. 19.
Mercury Sozoiodolate Solution, The Journal, Feb. 13, 1909, p. 573;
Reports Chem. Lab., 1909, p. 19.
Merrell, W. S., Chemical Co.--
Casta-Flora, 118
Proteogens, 227, 445
Mervenol, 249
Mervenol (Hille Laboratories), Reports Council Pharm. & Chem., 1919,
p. 82.
Methaform, 212
Methaform (F. Stearns & Co.), Reports Council Pharm. & Chem., 1918,
p. 68.
Methyl-Phenol Serum (Cano), 251
Methyl-Phenol Serum (Cano) (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1919, p. 85.
Methyl-Santal (H. K. Mulford Co.), Reports Council Pharm. & Chem.,
1915, p. 173.
Metz, H. A., Laboratories, Inc.--
Anesthesin, 276
Parathesin, 276
Phenetidyl-Acetphenetidin Hydrochlorid (Holocain Hydrochlorid), 372
Procain-Novocain brand, 356
Micajah’s Suppositories, 241
Micajah’s Suppositories (Micajah & Co.), The Journal, Nov. 29, 1919,
p. 1715; Reports Council Pharm. & Chem., 1919, p. 49.
Micajah’s Wafers, 241
Micajah’s Wafers (Micajah & Co.), The Journal, Nov. 29, 1919, p. 1715;
Reports Council Pharm. & Chem., 1919, p. 49.
Micrococcus Catarrhalis-Combined-Bacterin, 184
Micrococcus Catarrhalis-Combined-Bacterin (The Abbott Laboratories),
The Journal, June 22, 1918, p. 1967; Reports Council Pharm. & Chem.,
1918, p. 11.
Micrococcus Neoformans Vaccine, Reports Council Pharm. & Chem., 1917,
p. 152.
Migrainin (Farbwerke-Hoechst Co.), The Journal, June 5, 1909, p. 1851;
Reports Council Pharm. & Chem., 1909, p. 105; Propaganda, ed. 9,
p. 135.
Miller’s Iod-Izd-Oil, 49
Millikin’s Acetylsalicylic Acid, 347
Minson’s Soluble Iodin “Kelpidine”, 161
Minson’s Soluble Iodin “Kelpidine” (J. J. Minson), Reports Council
Pharm. & Chem., 1917, p. 152.
Mist. Helonin Comp. (Schlotterbeck & Foss), The Journal, Dec. 18,
1915, p. 2186.
Mitchella Compound (Dr. J. H. Dye Medical Institute), Reports Council
Pharm. & Chem., 1912, p. 46.
Mixed Vaccine No. 40, Sherman’s, 188
Mixed Vaccine No. 40, Sherman’s (G. H. Sherman), The Journal, June 22,
1918, p. 1967; Reports Council Pharm. & Chem., 1918, p. 11.
Mon-Arsone, 302, 492
Mon-Arsone (The Hammer Laboratories Co.), The Journal, Feb. 26, 1921,
p. 595; June 18, 1921, p. 1781; Reports Chem. Labs., 1920, p. 67;
Reports Council Pharm. & Chem., 1921, p. 47.
Monsanto’s Acetylsalicylic Acid (Aspirin), 347
Morphin Sulphate Hypodermic Tablets, 566
Morphine Meconate, Reports Council Pharm. & Chem., 1919, p. 84.
Mother’s Cordial (Eli Lilly & Co.), The Journal, Aug. 31, 1912,
p. 735; Reports Council Pharm. & Chem., 1912, p. 46; Propaganda,
ed. 9, p. 410.
Mother’s Cordial (Ray Chemical Co.), Reports Council Pharm. & Chem.,
1912, p. 46.
Motherwort, Reports Council Pharm. & Chem., 1912, p. 44.
Mucol Powder (Mucol Co., Inc.), The Journal, Nov. 15, 1913, p. 1812;
Reports Council Pharm. & Chem., 1913, p. 43; Propaganda, ed. 9,
p. 329.
Mulene, 332
Mulene (Mulene Co.), The Journal, May 19, 1917, p. 1497.
Mulford, H. K., Company--
Acetanilid Compound--Mulford, 206
Concentrated Solution Sodium Hypochlorite, 358
Granular Effervescent Bromide, 206
Influenza Serobacterin Mixed--Mulford, 187
Iron Citrate Green, 115
Mustard, Cream of, 218
Muthol (Demuth’s Laboratories), The Journal, July 10, 1915, p. 175.
Mystic Chemical Company--Olio-Phlogosis, 79
Naphey’s Medicated Uterine Wafers, 107
Narkine (The Tilden Co.), The Journal, Oct. 24, 1908 p. 1439;
Propaganda, ed. 9, p. 329.
National Bio-Chemical Laboratory (Therapeutic Leaves), 458
National Drug Company--
Brom-I-Phos, 136
“National Iodine Solution”, 300
National Formulary--a review of the fourth edition, 535
“National Iodine Solution”, 300
National Iodine Solution (National Drug Co.), The Journal, June 4,
1921, p. 1592; Reports Council Pharm. & Chem., 1921, p. 50.
National Laboratories of Pittsburgh--
Anti-Syphilitic Compound (Sweeny), 266, 268, 330
Anti-Tuberculous Lymph Compound (Sweeny), 266
National Medical University, 410
Natrium Compound, Pulvoids. See Pulvoids Natrium Compound.
Natura Company--“Akoz”, 328
Nazol (Nazol Antiseptic Co.), Reports Council Pharm. & Chem., 1918,
p. 81.
Neisser Serobacterin Mixed (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1916, p. 67.
Nelson, Baker & Co.--Eupeptic Hypophosphites, 83
Nephritin (Reed & Carnrick Co.), The Journal, Oct. 5, 1907, p. 1198;
Reports Council Pharm. & Chem., 1905-8, p. 79.
Nephroson (Wm. S. Merrell Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 39.
Nerve Vitalizer, Wheeler’s (J. W. Brant Co., Ltd.), The Journal,
April 11, 1908, p. 1206; Reports Chem. Lab., to 1909, p. 66;
Propaganda, ed. 9, p. 411.
Neuralgic Pills, 566
Neurilla (Dad Chemical Co.), The Journal, March 27, 1915, p. 1093;
Reports Council Pharm. & Chem., 1915, p. 20; Propaganda, ed. 9,
p. 136.
Neurocaine (Schieffelin & Co.), Reports Council Pharm. & Chem.,
1915, p. 173.
Neuro-Lecithin, 53
Neuro-Lecithin-Abbott (The Abbott Laboratories), Reports Council
Pharm. & Chem., 1915, p. 122.
Neuro Phosphates, Eskay’s, 146
Neuro Phosphates, Eskay’s (Smith, Kline & French Co.), The Journal,
Sept., 29, 1917, p. 1102; Reports Council Pharm. & Chem., 1917,
p. 52.
Neurosine (Dios Chemical Co.), The Journal, Jan. 9, 1915, p. 165;
April 27, 1918, p. 1251; Reports Council Pharm. & Chem., 1914,
p. 86; Propaganda, ed. 9, p. 139.
Neurosine and the original package evil, 404
New York Intravenous Laboratory--
Arseno-Meth-Hyd, 231
Loeser’s Intravenous Solutions, 299
New York Pharmacal Association--Lactopeptine and Elixir
Lactopeptine, 43
“Nikalgin”, 467
Noitol (Wheeler Chemical Works), The Journal, May 21, 1910, p. 1704;
Reports Chem. Lab., 1910, p. 45; Propaganda, ed. 9, p. 245.
Normal Horse Serum, Sterile (National Vaccine and Antitoxin
Institute), Reports Council Pharm. & Chem., 1921, p. 53.
Normal Phenol Serum (Cano), 251
Normal Phenol Serum (Cano) (H. K. Mulford Co.), Reports Council Pharm.
& Chem., 1919, p. 85.
Noron (The Heron Company), Reports Council Pharm. & Chem., 1921,
p. 53.
Norwich Pharmacal Company--Alfatone, 28
Nose-Ions (Nose-Ions Company), The Journal, Dec. 4, 1915, p. 2026;
Reports Chem. Lab., 1915, p. 123.
Nostrums in retrospect, 379
Nostrums, Shotgun, 398
Nourry Wine (E. Fougera & Co., Inc.), The Journal, Dec. 12, 1914,
p. 2150; Reports Council Pharm. & Chem., 1914, p. 74; Propaganda,
ed. 9, p. 115.
Novocain, Procain, 375
Novocaine, 355
Nuclein, Reports Council Pharm. & Chem., 1921, p. 54.
Nuclein, Triple Arsenates with, 256
Nucleinic Acid, Reports Council Pharm. & Chem., 1921, p. 54.
Nujol, 108
Nujol (Standard Oil Co. of New Jersey), The Journal, July 10, 1915,
p. 175; Reports Council Pharm. & Chem., 1916, p. 68.
Number “3”, 244, 247
Number “3” (Chlorine Products Company, Inc.), Reports Council Pharm.
& Chem., 1919, p. 70.
Nutone, 162
NuTone (NuTone Company), Reports Council Pharm. & Chem., 1917, p. 154.
Nutrient Wine of Beef Peptone (Armour & Co.), The Journal, May 11,
1907, p. 1612; Reports Council Pharm. & Chem., 1905-8, opp. p. 64;
Propaganda, ed. 9, p. 133.
Nutritive Liquid Peptone (Parke, Davis & Co.), The Journal, May 11,
1907, p. 1612; Reports Council Pharm. & Chem.,1905-8, opp. p. 64;
Propaganda, ed. 9, p. 133.
Nutrolactis, 131
Nutrolactis (The Nutrolactis Co.), The Journal, May 26, 1917, p. 1570;
Reports Council Pharm. & Chem., 1917, p. 24.
Nuxated Iron (Dae Health Laboratories), The Journal, Oct. 21, 1916,
p. 1244; Oct. 28, 1916, p. 1309; Nov. 4, 1916, p. 1376; Feb. 24,
1917, p. 642; Reports Chem. Lab., 1916, p. 29.
Oats, Reports Council Pharm. & Chem., 1912, p. 44.
Ogden, Willard Ealon, and his cure for piles, 538
Ohio State Department of Health protests use of name in advertisements
of Proteogens, 446
Ohmann-Dumesnil, A. H., 531
Oleum Iodine, B. oleum iodine, 198
Olio-Phlogosis, 79
Olio-Phlogosis (Mystic Chemical Company), The Journal, Aug. 19, 1916,
p. 631; Reports Council Pharm. & Chem., 1916, p. 10.
Olive Oil and Hypophosphites, Maltine with, 84
Ophthalmol-Lindemann, 189
Ophthalmol-Lindemann (Innis, Speiden & Co.), The Journal, July 6,
1918, p. 59; Reports Council Pharm. & Chem., 1918, p. 21.
Orchitic Fluid Tablets (New Animal Therapy Co.), The Journal, Dec. 14,
1912, p. 2176; Propaganda, ed. 9, p. 317.
Orsudan (Burroughs Wellcome & Co.), The Journal, April 16, 1910,
p. 1323.
Oscilloclast, 472
Osmium Tetroxide, Reports Council Pharm. & Chem., 1921, p. 55.
Ottofy, L. M., and The Allied Medical Associations of America, 487
Ova Mammoid (Lowenthal), 528
Oxychlorine (Oxychlorine Co.), The Journal, July 6, 1907, p. 54;
Reports Council Pharm. & Chem., 1905-8, p. 68; Propaganda, ed. 9,
p. 147.
Oxydendron Compound, Fluidextract (Nelson, Baker & Co.), Reports
Council Pharm. & Chem., 1912, p. 43.
Oxygen Water, Aquazone, 290
Oxyl-Iodide, 304
Oxyl-Iodide (Eli Lilly and Co.), The Journal, July 2, 1921, p. 57;
Reports Council Pharm. & Chem., 1921, p. 56.
Oxyntin (Fairchild Bros. and Foster), Reports Council Pharm. & Chem.,
1915, p. 174.
Palmetto Compound (Wm. S. Merrell Chem. Co.), Reports Council Pharm.
& Chem., 1912, p. 44.
Palpebrine (Dios Chemical Co.), The Journal, Jan. 9, 1915, p. 167;
Reports Council Pharm. & Chem., 1914, p. 86; Propaganda, ed. 9,
p. 139.
Pam-ala (Pam-Ala Co.), The Journal, Feb. 28, 1914, p. 715; Propaganda,
ed. 9, p. 149.
Pancreas Comp., Caps, 219
Pancreopepsin, Liquid (Wm. R. Warner & Co.), The Journal, Feb. 9,
1907, p. 533.
Pan-peptic Elixir (Sharp & Dohme), The Journal, Feb. 9, 1907, p. 533.
Papain, The Journal, Feb. 9, 1907, p. 522.
Pa-pay-ans, Bell (Bell & Co.): See Bell-ans.
Papine (Battle & Co.), The Journal, April 29, 1911, p. 1278; Reports
Chem. Lab., 1911, p. 82; Propaganda, ed. 9, p. 330.
Para Coto, Reports Council Pharm. & Chem., 1913, p. 39.
Paracotoin, Reports Council Pharm. & Chem., 1913, p. 39.
Paraffin Films, 330
Paraffin Films, formula for, 333
Paraffin, Stanolind Liquid, 214
Paraffins and paraffin preparations, examination of, 334
Parathesin, 276
Parathesin (H. A. Metz Laboratories, Inc.), The Journal, Nov. 13,
1920, p. 1358; Reports Council Pharm. & Chem., 1920, p. 27.
Parke, Davis & Company--
Apothesine, 260
Corpora Lutea (Soluble Extract), 128
Phylacogens, 441
Pituitary Extract, 550
Pituitrin, 550
Ricord Pills, 468
Silvol, 189
Therapeutic Notes, 550
Thyreoidectin, 202
Parresine, 332
Pasadyne (John B. Daniel), The Journal, March 8, 1913, p. 766;
Propaganda, ed. 9, p. 332.
Pas-Avena (Pas-Avena Chemical Company), The Journal, March 7, 1908,
p. 783; Reports Chem. Lab., to 1909, p. 69; Propaganda, ed. 9,
p. 333.
Pasiflora, The Journal, March 19, 1910, p. 983; Reports Council Pharm.
& Chem., 1912, p. 38; Propaganda, ed. 9, p. 156.
Pasiflora Incarnata, Daniel’s Concentrated Tincture of (John B.
Daniel), The Journal, March 19, 1910, p. 983; Reports Council Pharm.
& Chem., 1910, p. 44; 1912, p. 38; Propaganda, ed. 9, p. 156.
Pasteur Chemical Company--Thermozine, 334
Patch, E. L., Co.--Formitol Tablets, 236, 271
Patent-Law Revision, need for, 177
Patent Laws and Patent Office Practice, 542
Patent Laws, archaic, 543
Patent medicine, physicians not against patent medicine but for
protection of public, 513
Patenting therapeutic agents, 544
Patents perpetuated by trade names, 544
Pautauberge’s Solution (Geo. J. Wallau, Inc.), The Journal, March 7,
1910, p. 1560.
Peacock’s Bromides, 400
Pepsin and Pancreatin Compound, Elixir (Eli Lilly & Co.), The Journal,
Feb. 6, 1907, p. 533.
Pepsin and Pancreatin Compound, Tablets (Parke, Davis & Co.), Reports
Council Pharm. & Chem., 1912, p. 40.
Pepsin and Pancreatin, Elixir (Eli Lilly & Co.; Sharp & Dohme; Smith,
Kline & French Co.; F. Stearns & Co.; Wm. R. Warner & Co.), The
Journal, Feb. 9, 1907, p. 533.
Pepsin and Pancreatin with Caffein, Elixir (Eli Lilly & Co.; Parke,
Davis & Co.), The Journal, Feb. 9, 1907, p. 533.
Pepsin, Bismuth and Pancreatin, Elixir (Parke, Davis & Co.; Sharp
& Dohme; Smith, Kline & French Co.; F. Stearns & Co.), The Journal,
Feb. 9, 1907, p. 533.
Pepsin, Bismuth, Strychnin and Pancreatin, Elixir (Parke, Davis
& Co.), The Journal, Feb. 9, 1907, p. 533.
Pepsin, Elixir Lactated (H. K. Mulford Co.; Parke, Davis & Co.; F.
Stearns & Co.), The Journal, Feb. 9, 1907, p. 533.
Pepsin, Pancreatin and Bismuth, Elixir (Eli Lilly & Co.), The Journal,
Feb. 9, 1907, p. 533.
Pepsin, Pancreatin, Bismuth and Strychnin, Elixir (Eli Lilly & Co.),
The Journal, Feb. 9, 1907, p. 533.
Pepsin, Strychnin, Bismuth and Pancreatin, Elixir (Sharp & Dohme),
The Journal, Feb. 9, 1907, p. 533.
Peptenzyme, Elixir (Reed & Carnrick Co.), The Journal, Feb. 9, 1907,
p. 533; Oct. 5, 1907, p. 1198; Reports Council Pharm. & Chem.,
1905-8, p. 79.
Peptenzyme Powder (Reed & Carnrick Co.), The Journal, Oct. 5, 1907,
p. 1198; Reports Council Pharm. & Chem., 1905-8, p. 79.
Peptic Digestant (Columbus Pharmacal Co.), The Journal, Feb. 9, 1907,
p. 533.
Peptic Essence Comp., Peters’ (Arthur Peters & Co.), The Journal,
Feb. 9, 1907, p. 533.
Pepto-Mangan, 387
Pepto-Mangan (M. J. Breitenbach Co.), The Journal, Sept. 23, 1905,
p. 934; April 6, 1907, p. 1197; Dec. 29, 1917, p. 2202; Reports
Council Pharm. & Chem., 1914, p. 121; Propaganda, ed. 9, p. 159.
Peptone, Reports Council Pharm. & Chem., 1913, p. 41.
Peptonic Elixir (Wm. S. Merrell Chemical Co.), The Journal, May 11,
1907, p. 1612; Reports Council Pharm. & Chem., 1905-8, opp. p. 64;
Propaganda, ed. 9, p. 133.
Perfection Liquid Food (Perfection Liquid Food Co.), Reports Council
Pharm. & Chem., 1913, p. 44; Reports Chem. Lab., 1913, p. 80.
Pertussin, 467
Pertussin (Lehn & Fink), The Journal, March 8, 1913, p. 766;
Propaganda, ed. 9, p. 334.
Pertussis-Combined-Bacterin, 185
Pertussis-Combined-Bacterin (The Abbott Laboratories), The Journal,
June 22, 1918, p. 1967; Reports Council Pharm. & Chem., 1918, p. 11.
Peter, Arthur, & Co.--Syrupus Roborans (Syrup Hypophosphites Comp.
with Quinin, Strychnin and Manganese), 82
Petrolatum, Liquid, 526
Petrolatum, Liquid, Iodin in, 367
Petrolatum, Liquid, proprietary names for, 55
Petrolatum, liquid, solubility of Iodin in, 344
Pharmaceutical Barnums, 545
Pharmacopeia, the Ninth Decennial Revision, 546
Phecolates (F. Waldo Whitney), The Journal, Nov. 21, 1914, p. 1870;
Reports Council Pharm. & Chem., 1914, p. 127; Propaganda, ed. 9,
p. 174.
Phecolax (F. Waldo Whitney), The Journal, Nov. 21, 1914, p. 1870;
Reports Council Pharm. & Chem., 1914, p. 127; Propaganda, ed. 9,
p. 174.
Phecotones (F. Waldo Whitney), The Journal, Nov. 21, 1914, p. 1870;
Reports Council Pharm. & Chem., 1914, p. 127; Propaganda, ed. 9,
p. 174.
Phecozymes (F. Waldo Whitney), The Journal, Nov. 21, 1914, p. 1870;
Reports Council Pharm. & Chem., 1914, p. 127; Propaganda, ed. 9,
p. 174.
Phenalein (Pax Chemical Co.), The Journal, April 30, 1910, p. 1458;
Propaganda, ed. 9, p. 344.
Phenalgin, 393
Phenalgin (Etna Chemical Co.), The Journal, June 3, 1905, p. 1791;
Jan. 27, 1912, p. 293; Feb. 8, 1918, p. 337; Reports Council Pharm.
& Chem., 1905-8, p. 8; Propaganda, ed. 9, pp. 10, 335.
Phenetidyl-Acetphenetidin Hydrochlorid (Holocain Hydrochlorid), 372
Pheno-Bromate (Pheno-Bromate Co.), The Journal, July 14, 1906, p. 125;
April 18, 1908, p. 1282; Propaganda, ed. 9, p. 343.
Phenol, Methyl-Phenol Serum (Cano), 251
Phenol Serum, Normal (Cano), 251
Phenol Sodique (Hance Bros. & White), The Journal, Nov. 9, 1907,
p. 1617; Reports Council Pharm. & Chem., 1905-8, p. 99;
Propaganda, ed. 9, p. 175.
Phenolax Wafers (Upjohn Co.), The Journal, April 30, 1910, p. 1458;
Propaganda, ed. 9, p. 344.
Phenolphthalein Laxative (El Zernac Co.), The Journal, April 30, 1910,
p. 1458; Propaganda, ed. 9, p. 344.
Phenylcinchoninic Acid, U. S. P., 373
Phillips’ Phospho-Muriate of Quinine Comp., 197
Phosphates, Wheeler’s Tissue, 129, 463
Phosphoglycerate of Lime (Chapoteaut), 95
Phosphoglycerate of Lime (Chapoteaut) (E. Fougera and Co., Inc.), The
Journal, Sept. 30, 1916, p. 1034; Reports Council Pharm. & Chem.,
1916, p. 35.
Phospho-Muriate of Quinine Comp., Phillips’, 197
Phospho-Muriate of Quinine Comp.-Phillips (Charles H. Phillips
Chemical Co.), The Journal, Oct. 19, 1918, p. 1335; Reports Council
Pharm. & Chem., 1918, p. 32.
Phosphorcin Compound, 94
Phosphorcin Compound (Organic Products Company), The Journal,
Sept. 30, 1916, p. 1033; Reports Council Pharm. & Chem., 1916,
p. 34.
Phosphorus, Amorphous, The Journal, March 7, 1914, p. 793; March 28,
1914, p. 1033; Propaganda, ed. 9, p. 478.
Phosphorus, Amorphous, Pill, S. & D. (Sharp & Dohme), The Journal,
March 7, 1914, p. 793; March 28, 1914, p. 1033; Propaganda,
ed. 9, 478.
Phosphorus Compound, Iron and Arsenic, Hypodermic Solution No. 13, 275
Phosphorus Tonic, Compound, Dowd’s (The Richardson Company), The
Journal, Dec. 20, 1913, p. 2258; Propaganda, ed. 9, p. 476.
Phospho-Vanadiol (Vanadium Chemical Co.), The Journal, Jan. 18, 1913,
p. 225; Reports Council Pharm. & Chem., 1913, p. 7; Propaganda,
ed. 9, p. 209.
Phylacogens, 441
Phylacogens (Parke, Davis & Co.), The Journal, Feb. 1, 1913, p. 384;
Feb. 22, 1913, pp. 602, 615; March 15, 1913, p. 849; Aug. 29, 1914,
p. 785; Nov. 15, 1919, p. 1542; Propaganda, ed. 9, p. 346.
Physicians’ Drug Syndicate--Thymozene, 432
Physician’s League of Illinois, 529
Physician’s stock in prescription products, 548
Phytin (A. Klipstein & Co.), The Journal, Jan. 30, 1915, p. 456;
Reports Council Pharm. & Chem., 1915, p. 131; Propaganda,
ed. 9, p. 178.
Pil. Cascara Compound-Robins, 117
Pil. Cascara Comp.-Robins (A. H. Robins Co.), The Journal, Jan. 27,
1917, p. 303; Reports Council Pharm. & Chem., 1916, p. 47.
Pil. Mixed Treatment (Chichester), 310
Pil. Mixed Treatment (Chichester) (Hillside Chemical Co.), The
Journal, Oct. 22, 1921, p. 1355; Reports Council Pharm. & Chem.,
1921, p. 60.
Pineal Gland-Armour, Desiccated (Armour & Co.), Reports Council Pharm.
& Chem., 1918, p. 69.
Pineal Gland, Desiccated, Armour, 213
Pineal Gland, Reports Council Pharm. & Chem., 1918, p. 69.
Pineal Gland Tablets--Armour, 213
Pineoleum advertising methods, 442
Pineoleum (The Pineoleum Company), The Journal, Nov. 1, 1919, p. 1380.
Pinus Canadensis, Kennedy’s, Dark: See Darpin.
Piperazine, 214
Piperazine (The Bayer Co., Inc.), Reports Council Pharm. & Chem.,
1918, p. 70.
Piperazine Water (Lehn & Fink), The Journal, Feb. 29, 1908, p. 704.
Pituitary Extract in labor, 550
Pituitary Gland Preparations, 549
Pituitrin, 550
Pix Cresol (Pix Cresol Chemical Co.), The Journal, June 10, 1911,
p. 1738; Reports Chem. Lab., 1911, p. 37; Propaganda, ed. 9, p. 247.
Placento-Mammary Comp., Caps, 219
Plantex, Proteogen No. 1 (Plantex) for cancer, 227
Plasmon (Plasmon Milk Products Co.), Reports Chem. Lab., 1914, p. 88.
Platt’s Chlorides, 263
Platt’s Chlorides (Henry B. Platt), The Journal, March 27, 1920,
p. 903; Reports Chem. Lab., 1920, p. 28; Reports Council Pharm.
& Chem., 1920, p. 8.
Plurasav, Young’s (The Plurasav Co., Columbus, Ohio), Reports Council
Pharm. & Chem., 1918, p. 82.
“Pluriglandular” mixtures, 218
Pluto Spring Water, Concentrated (French Lick Springs Hotel Co.), The
Journal, March 29, 1913, p. 1013.
Pneumonia, camphor in, 257
Pneumo-Staph-Strep. Bacterin, Special Bacterial Vaccine No. 3, 254
Pneumo-Staph-Strep-Coli Bacterin, Special Bacterial Vaccine No. 4, 254
Pneumo-Strep. Bacterin, Special Bacterial Vaccine No. 11, 254
Pneumo-Strep-Serum (H. K. Mulford Co.), The Journal, Jan. 31, 1920,
p. 342.
Pollantin, Fall (Fritzsche Bros.), Reports Council Pharm. & Chem.,
1916, p. 69.
Pollantin Powder, Fall (Fritzsche Bros.), Reports Council Pharm.
& Chem., 1916, p. 69.
Pollen Antigen (Lederle Antitoxin Laboratories), Reports Council
Pharm. & Chem., 1918, p. 65.
Pollen Antigen-Lederle (Fall Type) (Lederle Antitoxin Laboratories),
Reports Council Pharm. & Chem., 1921, p. 45.
Pollen Antigen-Lederle (Spring Type) (Lederle Antitoxin Laboratories),
Reports Council Pharm. & Chem., 1921, p. 45.
Ponca Compound, 28
Ponca Compound (Mellier Drug Co.), The Journal, July 17, 1915, p. 269;
Reports Council Pharm. & Chem., 1912, p. 46; 1914, p. 58.
Poslam (Emergency Laboratories), The Journal, May 22, 1909, p. 1678;
Reports Chem. Lab., 1909, p. 25.
Potassium Iodo-Resorcin Sulphonate, The Journal, Feb. 11, 1911,
p. 441; Reports Chem. Lab., 1911, p. 21.
Prepared Green Bone, Russell, 134
Prescription products, physician’s stock in, 548
Probilin Pills (Schering & Glatz, Inc.), The Journal, Aug. 24, 1907,
p. 702; Nov. 2, 1907, p. 1541; Reports Council Pharm. & Chem.,
1905-8, p. 70; Propaganda, ed. 9, p. 344.
Procain-Abbott, 356, 377
Procain (Calco), 377
Procain (Farbwerke-Hoechst Co.), 357, 377
Procain (Metz), 377
Procain (Novocain), 375
Procain-Novocain brand, 356
Procain Rector, 356, 377
Procain, standardization of, and examination of market supply, 355
Proprietaries, why they flourish, 552
Proprietary medicine, secret remedies and the principles of
ethics, 571
Prostoid (Lowenthal), 528
Proteal Therapy, 494
“Proteal Therapy” and Henry Smith Williams, 443
Proteals (Henry Smith Williams), The Journal, July 6, 1918, p. 58.
Protein Therapy, Nonspecific, 536
Proteogen No. 1 (Plantex) for cancer, 227
Proteogen No. 2 for rheumatism, 227
Proteogen No. 3 for tuberculosis, 227
Proteogen No. 4 for hay fever and bronchial asthma, 227
Proteogen No. 5 for dermatoses, 227
Proteogen No. 6 for chlorosis, 227
Proteogen No. 7 for secondary anemia, 227
Proteogen No. 8 for pernicious anemia, 227
Proteogen No. 9 for goitre, 227
Proteogen No. 10 for syphilis, 227
Proteogen No. 11 for gonorrhea, 227
Proteogen No. 12 for influenza and pneumonia, 227
Proteogens, 226, 445
Proteogens (Wm. S. Merrell Co.), The Journal, July 12, 1919, pp. 109
and 128; July 26, 1919, p. 288; Sept. 6, 1919, p. 781; Sept. 27,
1919, p. 1000; Oct. 11, 1919, p. 1152; Reports Council Pharm.
& Chem., 1919, p. 20.
Proteogens, alleged endorsement repudiated, 446
Proteogens, Dr. Broeman’s final report on, 450
Protonuclein, 59
Protonuclein (Reed & Carnrick Co.), The Journal, Oct. 5, 1907,
p. 1198; Oct. 24, 1908, p. 1388; Jan. 1, 1916, p. 48; Reports
Council Pharm. & chem., 1905-8, p. 79; Reports Council Pharm.
& Chem., 1915, p. 90; Propaganda, ed. 9, p. 348.
Protonuclein Beta, 59
Protonuclein Beta (Reed & Carnrick Co.), The Journal, Jan. 1, 1916,
p. 48; Reports Council Pharm. & Chem., 1915, p. 90.
Prunoids (Sultan Drug Co.), The Journal, April 30, 1910, p. 1458;
Jan. 2, 1915, p. 71; Reports Council Pharm. & Chem., 1914, p. 133;
Reports Chem. Lab., 1914, p. 63; Propaganda, ed. 9, pp. 178, 344.
Psora (Pix Cresol Co.), Reports Council Pharm. & Chem., 1912, p. 39.
Pulvane, 450
Pulvoids, Calcylates, 85
Pulvoids, Calcylates (Drug Products Company), The Journal, Sept. 9,
1916, p. 827; Reports Council Pharm. & Chem., 1916, p. 18.
Pulvoids Calcylates Compound, 226
Pulvoids Calcylates Compound (The Drug Products Co., Inc.), The
Journal, June 14, 1919, p. 1784; Reports Council Pharm. & Chem.,
1919, p. 19.
Pulvoids Natrium Compound, 108
Pulvoids Natrium Compound (Drug Products Company, Inc.), Reports
Council Pharm. & Chem., 1916, p. 69.
Purdue Frederick Company--Gray’s Glycerine Tonic, 24
Purgen (Lehn & Fink), The Journal, Jan. 5, 1907, p. 64; Sept. 14,
1907, p. 954; Propaganda, ed. 9, p. 349.
Pyo-atoxin (H. O. Hurley), The Journal, Feb. 14, 1914, p. 552; Reports
Chem. Lab., 1914, p. 32; Propaganda, ed. 9, p. 350.
Pyocyaneus Bacillus Vaccine, The Journal, May 18, 1918, p. 1486;
Reports Council Pharm. & Chem., 1918, p. 11.
Pyxol (Barrett Mfg. Co.), The Journal, Feb. 23, 1918, p. 559.
Quartonol Tablets, 94
Quartonol Tablets (Schering and Glatz, Inc.), The Journal, Sept. 30,
1916, p. 1033; Reports Council Pharm. & Chem., 1916, p. 34.
Quassia Compound Tablets, 306
Quassia Compound Tablets (Flint, Eaton and Company), The Journal,
July 9, 1921, p. 141; Reports Council Pharm. & Chem., 1921, p. 64.
Queen of the Meadow, Reports Council Pharm. & Chem., 1912, p. 45.
Quina LaRoche (E. Fougera & Co., Inc.), The Journal, March 21, 1908,
p. 978.
Quinin and Urea Hydrochlorid, 467
Quinin Arsenate, The Journal, July 16, 1910, p. 325; Reports Council
Pharm. & Chem., 1910, p. 73.
Quinin Glycerophosphate, Reports Chem. Lab., 1912, p. 107.
Quinin Laxative Tablets, 566
Quinine Comp., Phillips’ Phospho-Muriate of, 197
Rabbit-Foot Therapy, 571
Radelium and Radelium Generator (Radio-Active Water Company), Reports
Council Pharm. & Chem., 1915, p. 128.
Radio-Rem, 79
Radio-Rem Outfit No. 2, No. 3 (Schieffelin & Co.), The Journal,
Aug. 19, 1916, p. 631; Reports Council Pharm. & Chem., 1916, p. 9.
Radio-Rem Outfit C (Schieffelin & Co.), The Journal, Aug. 19, 1916,
p. 631; Reports Council Pharm. & Chem., 1916, p. 9.
Radium Solution for Intravenous Use, Standard (Radium Chemical Co.),
The Journal, June 26, 1915, p. 2156; Reports Council Pharm. & Chem.,
1915, p. 147.
Rahtjen, Philip, and his discoveries, 553
Rainey, James M., 528
Rattlesnake-Venom, The Journal, March 15, 1913, p. 850; March 29,
1913, p. 1001; June 7, 1913, p. 1811.
Rector Chemical Company--
Barbital, 371
Procain-Rector, 356, 377
Red Bone-Marrow--Armour, Extract of, 213
Red Bone-Marrow, Reports Council Pharm. & Chem., 1918, p. 69.
Red Bone-Marrow--Armour, Extract of (Armour & Co.), Reports Council
Pharm. & Chem., 1918, p. 69.
Red Mercuric Iodid (Mercury Biniodid) comparative symptoms resulting
from use of several oily suspensions of, 123
Redintol (Johnson & Johnson), The Journal, July 28, 1917, p. 306.
Reed and Carnrick--Protonuclein and Protonuclein Beta, 59
Reinschild Chemical Company--Iodo-Mangan, 106
Resinol (Resinol Chemical Co.), The Journal, Nov. 6, 1909, p. 1578;
Propaganda, ed. 9, p. 352.
Resor-Bisnol (Resor-Bisnol Chemical Co.), The Journal, June 1, 1912,
p. 1706; Reports Chem. Lab., 1912, p. 85; Propaganda, ed. 9, p. 353.
Respirazone (The Tilden Company), The Journal, June 14, 1913, p. 1899.
Restorative Capsules, 425
Rheumalgine, 23
Rheumalgine (Eli Lilly & Co.), The Journal, June 26, 1915, p. 2156;
Reports Council Pharm. & Chem., 1915, p. 148.
Rheumatic and Gout Pills, De Sanctis’, 363
Rheumatic Bacterin (Mixed), (No. 47), Swan’s (Swan-Myers Co.), The
Journal, Nov. 6, 1915, p. 1662; Reports Council Pharm. & Chem.,
1915, p. 160.
Rheume Olum (Rheumeolum Chemical Co.), The Journal, March 17, 1917,
p. 865;
Reports Council Pharm. & Chem., 1917, p. 19.
Ricinol-Grape Tape-Worm Remedy (Grape Capsule Co.), Reports Council
Pharm. & Chem., 1915, p. 174.
Ricord Pills and house organ therapeutics., 468
Riedel and Company, Inc.--Gonosan, 150
Robinol, 95
Robinol (John Wyeth & Bro.), The Journal, July 6, 1914, p. 49;
Sept. 30, 1916, p. 1034; Reports Council Pharm. & Chem., 1916,
p. 34; Propaganda, ed. 9, p. 353.
Robins, A. H., Company--
Campetrodin and Campetrodin No. 2, 193
Pil, Cascara Compound--Robins, 117
Robinson-Pettet Company--
Robinson’s Hypophosphites, 83
Saloform, 110
Robinson’s “Cure” for Cancer--Tekarkin, 458
Robinson’s Hypophosphites, 83
Roborans, Syrupus, (Syrup Hypophosphites Comp. with Quinin, Strychnin
and Manganese), 82
Rogers, L. D.--Auto-Hemic Serum, 409
Rogers, R. R., Chemical Company--Unctol, 166
Royal Thermophor Sales Co.--Thermor Waterless Hot Bottle, 329
Russell Emulsion, 134
Russell Emulsion (The Standard Emulsion Co.), The Journal, June 23,
1917, p. 1931; Reports Council Pharm. & Chem., 1917, p. 29.
Russell Prepared Green Bone, 134
Russell Prepared Green Bone (The Standard Emulsion Co.), The Journal,
June 23, 1917, p. 1931; Reports Council Pharm. & Chem., 1917, p. 29.
Sal-Codeia, Bell (Bell & Co.), The Journal, Nov. 4, 1905, p. 1422;
Propaganda, ed. 9, p. 357.
Sal Hepatica, 451
Sal Hepatica (Bristol-Myers Co.), The Journal, March 26, 1910,
p. 1071; Feb. 7, 1914, p. 427; April 12, 1919, p. 1078; Oct. 29,
1921, p. 1438; Reports Council Pharm. & Chem., 1914, p. 7;
Propaganda, ed. 9, p. 179.
Sal Hyl (New York Salesthyl Corporation), The Journal, Feb. 20, 1915,
p. 684; Reports Council Pharm. & Chem., 1915, p. 134.
Salacetin (Bell & Co.), The Journal, June 3, 1905, p. 1791; Reports
Council Pharm. & Chem., 1905-8, p. 8; Propaganda, ed. 9, p. 152.
Salen (A. Klipstein & Co.), Reports Council Pharm. & Chem., 1917,
p. 155.
Salenal (A. Klipstein & Co.), Reports Council Pharm. & Chem., 1917,
p. 155.
Salesthyl (New York Salesthyl Corporation), The Journal, Feb. 20,
1915, p. 684; Reports Council Pharm. & Chem., 1915, p. 134.
Salicon, 453
Salicylic Acid, “Natural,” The Journal, Sept. 20, 1913, p. 979;
Reports Council Pharm. & Chem., 1913, p. 23.
Saliodin (Saliodin Chemical Co.), The Journal, Oct. 26, 1907, p. 1453;
Reports Council Pharm. & Chem., 1905-8, p. 95; Propaganda, ed. 9,
p. 249.
Salit (Heyden Chemical Works), The Journal, June 5, 1909, p. 1852;
Reports Council Pharm. & Chem., 1909, p. 106.
Saloform, 110
Saloform (Robinson-Pettet Company), Reports Council Pharm. & Chem.,
1916, p. 71; Reports Chem. Lab., 1916, p. 36.
Salol Tablets, 566
Salvarsan: abrogate the patent, 493
Sanatogen (Bauer Chemical Co.), The Journal, April 20, 1912, p. 1216;
Dec. 6, 1913, p. 2085; March 28, 1914, p. 1035; Sept. 26, 1914,
p. 1127; Reports Chem. Lab., 1912, p. 71; Propaganda, ed. 9,
pp. 358, 378, 385.
de Sandfort’s Ambrine, 330
Sanmetto (The Od Chemical Co.), The Journal, July 8, 1905, p. 116;
March 13, 1915, p. 926; Reports Council Pharm. & Chem., 1915, p. 17;
Propaganda, ed. 9, p. 182.
Sanol (Expurgo Mfg. Co.),--See Expurgo Anti-Diabetes.
Santaiva, S. & D. Liquor, 211
Santal Midy Capsules (E. Fougera & Co.), The Journal, Oct. 9, 1920,
p. 1016.
Saphanol Aromatic (Saphanol Products Co.), Reports Council Pharm.
& Chem., 1921, p. 66.
Saphanol Concentrate (Saphanol Products Co.), Reports Council Pharm.
& Chem., 1921, p. 66.
Schering and Glatz, Inc.--
Arhovin, 243
Atophan, 313
Cinchophen (Phenylcinchoninic Acid, U. S. P.; Atophan), 373
Medinal, 239
Tonols (Schering’s Glycerophosphates), 94
Urotropin, 316
Schieffelin and Company--
Colalin, 203
Estivin, 466
Radio-Rem, 79
Schlotterbeck’s Solution Hypophosphites of Lime and Soda (Liq.
Hypophosphitum, Schlotterbeck’s), 83
Schmidt’s Antimeristem, 408
Schoonmaker Laboratories, Inc.--V-E-M, 166
Scopolamin-Morphin Mixtures, The Journal, Feb. 5, 1910, p. 446;
Feb. 12, 1910, p. 516; June 7, 1913, p. 1814; Reports Council Pharm.
& Chem., 1910, p. 11.
Scott Creosotonic, 192, 193
Scott Iodinized Emulsion, 192
Scullcap Compound, Fluidextract (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 43.
Secretin-Beveridge (James Wallace Beveridge), The Journal, Jan. 12,
1918, p. 116; Reports Council Pharm. & Chem., 1917, p. 120.
Secretin-Beveridge and the U. S. Patent Law, 170
Secretin-Beveridge, question of stability of, 171
Secretin, commercial preparations of, 75
Secretin, has it a therapeutic value?, 65
Secretin Preparations, So-called, 64, 454
Secretogen, 75, 110
Secretogen Elixir (G. W. Carnrick Co.), The Journal, Nov. 1, 1913,
p. 1649; May 1, 1915, p. 1518; Sept. 9, 1916, p. 828; Reports
Council Pharm. & Chem., 1915, p. 46; 1916, p. 72; Propaganda,
ed. 9, p. 185.
Secretogen Tablets (G. W. Carnrick Co.), The Journal, Nov. 1, 1913,
p. 1649; May 1, 1915, p. 1518; Jan. 15, 1916, pp. 178, 208; Sept. 9,
1916, p. 828; Reports Council Pharm. & Chem., 1915, pp. 46, 96, 99;
1916, p. 72; Propaganda, ed. 9, p. 185.
Sedobrol “Roche” (Hoffmann-LaRoche Chemical Works), The Journal,
Jan. 2, 1915, p. 71; Reports Council Pharm. & Chem., 1914, p. 134.
Seleni-Bascca, 416
Seleni-Bascca (Cosmopolitan Cancer Research Society), The Journal,
Nov. 19, 1921, p. 1672.
Selenium in cancer, 506
Semprolin (W. Browning & Co.), The Journal, July 10, 1915, p. 175.
Seng, 55
Seng (Sultan Drug Co.), Reports Council Pharm. & Chem., 1912, p. 42;
1915, p. 129.
Serum Vaccine, Bruschettini (R. G. Berlingieri), The Journal, Nov. 21,
1914, p. 1870; Reports Council Pharm. & Chem., 1914, p. 127.
Serums, 521
Seufert, L. B., Secretary, Direct Sales Company, 510
Seven-Bark, Reports Council Pharm. & Chem., 1912, p. 45.
Sevetol (John Wyeth & Bro.), The Journal, July 6, 1914, p. 49;
Propaganda, ed. 9, p. 353.
Sextonol Tablets, 94
Sextonol Tablets (Schering & Glatz, Inc.), The Journal, Sept. 30,
1916, p. 1033; Reports Council Pharm. & Chem., 1916, p. 34.
Sharp and Dohme--
Elixir Glycerophosphates, Nux Vomica and Damiana, 95
Liquor Santaiva, 211
Surgodine, 180
Sherman, G. H., on vaccines in toxic conditions, 560
Sherman’s Mixed Vaccine No. 40. See Mixed Vaccine No. 40, Sherman’s.
Shotgun Nostrums, 398
Silvol, 189
Sinclair, Upton, defense of Abrams by, 477
Sinkina (Metropolitan Pharmacal Co.), The Journal, Sept. 27, 1913,
p. 1056; Reports Council Pharm. & Chem., 1913, p. 24; Propaganda,
ed. 9, p. 188.
Sirolin (Sirolin Co.), The Journal, June 21, 1913, p. 1974.
Smith, Kline & French Co.--Eskay’s Neuro Phosphates, 46
Soamin, 253
Soamin Tabloid (Burroughs Wellcome & Co.), Reports Council Pharm.
& Chem., 1919, p. 89.
Sodium Acetate in warming bottles, 329
Sodium Cacodylate in syphilis, 555
Sodium Carbonate and Sodium Chloride Mixture for making Fisher’s
Hypertonic Alkaline Solution (E. R. Squibb & Sons), Reports Council
Pharm. & Chem., 1917, p. 147.
Sodium Glycerophosphate, 99
Sodium Glycerophosphate, Reports Council Pharm. & Chem., 1916, p. 52.
Sodium Hypochlorite-Mulford, Concentrated Solution, 358
Sodium Hypochlorite Solutions (“Chlorinated Soda” Solutions),
Deterioration of, 358
Sodium Salicylate, “Natural,” The Journal, Sept. 20, 1913, p. 979;
Reports Council Pharm. & Chem., 1913, p. 23.
Sodium Salicylate, Strontium Salicylate not superior to, 572
Sodium Salicylate Tablets, 566
Sofos (General Chemical Co.), Reports Council Pharm. & Chem., 1921,
p. 67.
Solution Hypophosphites of Lime and Soda (Liq. Hypophosphitum,
Schlotterbeck’s), 83
Solution Hypophosphites of Lime and Soda, Schlotterbeck’s (Liq.
Hypophosphitum, Schlotterbeck’s), (Schlotterbeck and Foss Co.), The
Journal, Sept. 2, 1916, p. 761; Reports Council Pharm. & Chem.,
1916, p. 14.
Somnoform, 255
Somnoform (Stratford-Cookson Co.), Reports Council Pharm. & Chem.,
1919, p. 90.
Somnos (H. K. Mulford Co.), The Journal, Sept. 15, 1906, pp. 863, 872;
Sept. 29, 1906, p. 1033; Reports Council Pharm. & Chem., 1905-8,
p. 12; Propaganda, ed. 9, p. 193.
Sourwood, Reports Council Pharm. & Chem., 1912, p. 45.
Sourwood Compound, Elixir (Eli Lilly & Co.), Reports Council Pharm.
& Chem., 1912, p. 45.
Sourwood Compound, Elixir (Parke, Davis & Co.), Reports Council Pharm.
& Chem., 1912, p. 39.
Sourwood Compound (Special), Elixir (Parke, Davis & Co.), Reports
Council Pharm. & Chem., 1912, p. 45.
Special Bacterial vaccine Nos. 2, 3, 4, 5, 11, 15, and 16, 254
Spermin, Poehl (Prof. Dr. v. Poehl & Soehne), The Journal, April 15,
1911, p. 1132; Propaganda, ed. 9, p. 395.
Spirocide, 296
Spirocide (The Spirocide Corp.), The Journal, Jan. 22, 1921, p. 259;
July 30, 1921, p. 394; Reports Chem. Lab., 1920, p. 58; Reports
Council Pharm. & Chem., 1920, p. 46.
Spondylotherapy, 472
Squaw-Vine, Reports Council Pharm. & Chem., 1912, p. 45.
Squaw-Vine and Black-Haw Compound, Elixir (Eli Lilly & Co.), Reports
Council Pharm. & Chem., 1912, p. 46.
Squaw-Vine Compound, Syrup (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 46.
Squibb, E. R., and Sons--
Acetylsalicylic Acid, 347
Iron Citrate Green, 115
S. S. Products Company--Arsenoven S. S., 231
Standard Appliance Company--Uri-Na Test, 498
Standard Emulsion Company--
Russell Emulsion and Russell Prepared Green Bone, 134
Standard Oil Company of Indiana--
Stanolind Liquid Paraffin, 214
Stanolind Surgical Wax, 337
Standard Oil Company of New Jersey--Nujol, 108
Stannoxyl, 469
Stannoxyl (E. Fougera & Co.), The Journal, March 6, 1920, p. 692.
Stanolind Liquid Paraffin, 214
Stanolind Liquid Paraffin (Standard Oil Company of Ind.), Reports
Council Pharm. & Chem., 1918, p. 72.
Stanolind Surgical Wax, 337
Staph-Strep. Bacterin, Vaccine No. 2, Special Bacterial, 254
Stearns, Frederick & Co.--
Alphozone, 99
Methaform, 212
Stearns’ Wine, 59
Stearns’ Wine, 59
Sterling Products Company and “Aspirin Bayer”, 485
“Sterling Violet Ray Generator”, 572
Stillingia Compound, Elixir (Hance Bros. & White; Ray Chemical Co.;
Smith, Kline & French Co.), Reports Council Pharm. & Chem., 1912,
p. 47.
Stillingia Compound, Fluidextract (H. K. Mulford Co.), Reports
Council Pharm. & Chem., 1912, p. 42.
Stillingia Compound, Syrup (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 42.
Stock, Physician’s, in Prescription Products, 548
Stone Root, Reports Council Pharm. & Chem., 1912, p. 46.
Stratford-Cookson Company--Somnoform, 255
Streptococcus-Rheumaticus-Combined-Bacterin, 185, 186
Streptococcus-Rheumaticus-Combined-Bacterin (The Abbott Laboratories),
The Journal, June 22, 1918, p. 1967; Reports Council Pharm. & Chem.,
1918, p. 11.
Streptococcus-Viridans-Combined-Bacterin, 185, 186
Streptococcus-Viridans-Combined-Bacterin (The Abbott Laboratories),
The Journal, June 22, 1918, p. 1967; Reports Council Pharm. & Chem.,
1918, p. 11.
Strontium Salicylate not superior to Sodium Salicylate, 572
Strychnin Arsenate, The Journal, Sept. 24, 1910, p. 1128; Reports
Council Pharm. & Chem., 1910, p. 74.
Stypticin, 240
Stypticin, The Journal, Nov. 22, 1919, p. 1628; Reports Council Pharm.
& Chem., 1919, p. 48.
Styptol, 240
Styptol (E. Bilhuber), The Journal, Nov. 22. 1919, p. 1628; Reports
Council Pharm. & Chem., 1919, p. 48.
Styptysate, 318
Succinate of Soda, Bile Salts and Phenolphthalein, Capsules of, 208
Succinate of Soda, Holadin and Bile Salts, Capsules of, 208
Succinolac (Succinolac Company), Reports Council Pharm. & Chem., 1916,
p. 79.
Succus Alterans (Eli Lilly & Co.), The Journal, June 26, 1909,
p. 2115; Reports Council Pharm. & Chem., 1909, p. 107; Propaganda,
ed. 9, p. 195.
Succus Cineraria Maritima, 455
Succus Cineraria Maritima, Walker (Walker Pharmacal Co.), The Journal,
Nov. 11, 1911, p. 1630; March 17, 1917, p. 864; Reports Council
Pharm. & Chem., 1911, p. 48; Propaganda, ed. 9, p. 50.
Sukro-Serum, 273
Sukro-Serum (Anglo-French Drug Co.), The Journal, Aug. 21, 1920,
p. 556; Reports Council Pharm. & Chem., 1920, p. 23.
Sulfo-Selene, 417
Sulfuryl Monal, 86
Sulfuryl Monal (Geo. J. Wallau, Inc.), The Journal, Sept. 16, 1916,
p. 895; Reports Council Pharm. & Chem., 1916, p. 22; Reports Chem.
Lab., 1916, p. 23.
Sulpho-Lythin (Laine Chemical Co.), The Journal, Dec. 8, 1906,
p. 1930; Reports Council Pharm. & Chem., 1905-8, p. 34; Propaganda,
ed. 9, p. 196.
Sulpho-Selene (C. H. Walker), The Journal, April 17, 1915, p. 1283;
Dec. 16, 1915, p. 1864; Reports Council Pharm. & Chem., 1915, p. 28;
1916, p. 80.
Sultan Drug Co.--
Cactina Pillets, 391
Seng, 55
Supsalvs, 274
Supsalvs (Anglo-French Drug Co.). The Journal, Oct. 30, 1920, p. 1219;
Reports Council Pharm. & Chem., 1920, p. 25.
Surgodine, 180
Surgodine (Sharp & Dohme), The Journal, Jan. 26, 1918, p. 257; Reports
Council Pharm. & Chem., 1917, p. 134; Reports Chem. Lab., 1917,
p. 59.
Swan-Myers Company--Di-Crotalin, 465
Sweeny, Anti-Tuberculous Lymph Compound, 266
Sweeny’s Anti-Syphilitic Compound, 268, 330
Synthetic drugs, American-Made, 344, 369
Synthetic drug situation, 376
Syphilis, sodium cacodylate in, 555
Syphilodol, 359, 470
Syphilodol (French Medicinal Company, Inc.), The Journal, May 18,
1918, p. 1485.
Syrup Balsamea, 268
Syrup Cephaelin-Lilly, 203
Syrup Cocillana Compound (Parke, Davis & Co.), The Journal, March 18,
1911, p. 834; Feb. 15, 1913, p. 537; Reports Council Pharm. & Chem.,
1912, p. 43; Propaganda, ed. 9, p. 396.
Syrup Emetic-Lilly, 203
Syrup Emetic-Lilly (Eli Lilly & Co.). Reports Council Pharm. & Chem.,
1918, p. 52.
Syrup, Fellows’, of Hypophosphites, 82
Syrup, Gardner’s, of Ammonium Hypophosphite, 100
Syrup of Ammonium Hypophosphite, Gardner’s, 100
Syrup of Ammonium Hypophosphite, Gardner’s (R. W. Gardner), Reports
Council Pharm. & Chem., 1916, p. 55.
Syrup of Hydriodic Acid, Gardner’s (R. W. Gardner), The Journal,
Nov. 14, 1908, p. 1712; Reports Council Pharm. & Chem., 1905-8,
p. 200; Propaganda, ed. 9, p. 97.
Syrup of Hypophosphites Comp. (Lime and Soda) McArthur’s, 84
Syrup of the Hypophosphites Comp. (Lime and Soda), McArthur’s
(McArthur Hypophosphite Co.), The Journal, Sept. 2, 1916, p. 761;
Reports Council Pharm. & Chem., 1916, p. 16.
Syrup of Hypophosphites, Fellow’s, 82
Syrup of Hypophosphites, Fellows’ (Fellows Medical Mfg. Co.), The
Journal, Sept. 2, 1916, p. 760; Feb. 16, 1918, p. 478; Reports
Council Pharm. & Chem., 1916, p. 13.
Syrup Iron Iodid, U. S. P., 566
Syrup Leptinol (Balsamea Co.), The Journal, June 5, 1920, p. 1591;
Reports Council Pharm. & Chem., 1920, p. 15.
Syrup Leptinol (formerly Syrup Balsamea), 268
Syrup of Malt Williams’ (American Malt Extract Co.), The Journal,
Sept. 4, 1915, p. 895; Reports Council Pharm. & Chem., 1915, p. 155.
Syrup of Thyme, 467
Syrupus Roborans (Syrup Hypophosphites Comp. with Quinin, Strychnin
and Manganese), 82
Syrupus Roborans (Syrup Hypophosphites Comp. with Quinin, Strychnin
and Manganese) (Arthur Peter & Co.), The Journal, Sept. 2, 1916,
p. 760; Reports Council Pharm. & Chem., 1916, p. 14.
Tablets: dependability of dosage, 556
Tablets Formothalates, 256
Tablets Formothalates (Tailby-Nason Company), Reports Council Pharm.
& Chem., 1919, p. 92.
Tablogestin (F. H. Strong Co.), The Journal, Dec. 11, 1915, p. 2108.
Tailby-Nason Company--Tablets Formothalates, 256
Taka-Diastase (Parke, Davis & Co.), The Journal, July 11, 1908,
p. 140; July 6, 1912, p. 50; Reports Council Pharm. & Chem., 1905-8,
p. 110; 1912, p. 14; Propaganda, ed. 9, p. 62.
Taka-Diastase, Liquid (Parke, Davis & Co.), The Journal, July 11,
1908, p. 140; July 6, 1912, p. 50; Reports Council Pharm. & Chem.,
1905-8, p. 110; 1912, p. 14; Propaganda, ed. 9, p. 62.
Tannyl (Charles Goslar), Reports Chem. Lab., 1912, p. 108.
Tartarlithine (Tartarlithine Co., McKesson & Robbins), The Journal,
April 13, 1907, p. 1284; Propaganda, ed. 9, p. 401.
Taurocol Compound Tablets (Paul Plessner Company), The Journal,
April 24, 1915, p. 1441; Reports Council Pharm. & Chem., 1915,
p. 143; Propaganda, ed. 9, p. 198.
Taurocol Tablets (Paul Plessner Company), The Journal, April 24, 1915,
p. 1441; Reports Council Pharm. & Chem., 1915, p. 143; Propaganda,
ed. 9, p. 198.
Tekarkin, 458
Tekarkin (National Bio-Chemical Laboratory), The Journal, May 28,
1921, p. 1514; Nov. 19, 1921, p. 1675.
Terpin Hydrate with Codein Sulphate, Elixir, The Journal, April 15,
1916, p. 1199.
Textbooks, fallibility of, 515
Thalosen (The Abbott Laboratories), The Journal, April 30, 1910,
p. 1458; Propaganda, ed. 9, p. 344.
Therapeutic evidence: its crucial test, 557
Therapeutic Leaves, 458
Therapeutic Notes, 550
Therapeutic Notes, Ricord Pills written up in, 468
Thermor Waterless Hot Bottle, 329
Thermozine, 332, 334
Thermozine (Pasteur Chemical Co.), The Journal, May 19, 1917, p. 1497.
Thialion, 470
Thialion (Vass Chemical Co.), The Journal, Nov. 3, 1906, p. 1500;
Reports Council Pharm. & Chem., 1905-8, p. 26; Propaganda, ed. 9,
p. 205.
Thioform (Otto Hann & Bro), Reports Chem. Lab., to 1909, p. 79.
Thiosinamine and Thiosinamine Compounds, Reports Council Pharm.
& Chem., 1920, p. 68.
Thoxos (John Wyeth & Bro.), The Journal, March 21, 1914, p. 949;
Reports Chem. Lab., 1914, p. 41; Propaganda, ed. 9, p. 402.
Three Chlorides (Henry), (Henry Pharmacal Co.), The Journal, Feb. 6,
1915, p. 528; Reports Council Pharm. & Chem., 1915, p. 9; Reports
Chem. Lab., 1914, p. 65; Propaganda, ed. 9, p. 198.
Thyme, Syrup of, 467
Thymozene, 432
Thymus, Desiccated, Armour, 213
Thymus Gland, Reports Council Pharm. & Chem., 1918, p. 69.
Thymus-Gland-Armour, Desiccated (Armour & Co.), Reports Council Pharm.
& Chem., 1918, p. 69.
Thymus Tablets--Armour, 213
Thyreoidectin, 202
Thyreoidectin (Parke, Davis & Co.), Reports Council Pharm. & Chem.,
1918, p. 50.
Thyroid Comp., Caps, 219
Thyroid Preparations (Antithyroidin-Moebius and Thyreoidectin), 202
Thyro-Ovarian Comp., Caps, 219
Tilden Company--
Elixir Iodo-Bromide of Calcium Comp. “Without Mercury” and “With
Mercury”, 52
Firolyptol Plain and Firolyptol with Kreosote, 120
Firwein, 119
Tincture of Digitalis (Upsher Smith), Reports Council Pharm. & Chem.,
1920, p. 52.
Tissue Phosphates, Wheeler’s, 129, 463
Tissue Phosphates, Wheeler’s (T. B. Wheeler, M.D., Company), The
Journal, May 5, 1917, p. 1336; Sept. 22, 1917, p. 1010; Reports
Council Pharm. & Chem., 1917, p. 21; Reports Chem. Lab., 1917,
p. 13.
Tonga, The Journal, May 10, 1913, p. 1477; Reports Council Pharm.
& Chem., 1912, p. 46.
Tonga and Salicylates, Elixir (Sharp & Dohme), The Journal, May 10,
1913, p. 1478; Reports Council Pharm. & Chem., 1912, p. 47.
Tonga Compound, Elixir (Hance Bros. & White; Eli Lilly & Co.; Nelson
Baker & Co.; Ray Chemical Co.; F. Stearns & Co.), The Journal,
May 10, 1913, p. 1478; Reports Council Pharm. & Chem., 1912, p. 47.
Tonga Compound, Elixir (Wm. S. Merrell Chemical Co.), Reports Council
Pharm. & Chem., 1912, p. 46.
Tonga Compound, Elixir (Parke, Davis & Co.; Wm. R. Warner & Co.), The
Journal, May 10, 1913, p. 1478.
Tonga Compound (Special), Elixir (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 47.
Tonga Salicylates, Elixir (Wm. S. Merrell Chemical Co.), The Journal,
May 10, 1913, p. 1478.
Tongaline, 26, 400
Tongaline (Mellier Drug Co.), The Journal, May 10, 1913, p. 1477;
July 17, 1915, p. 269; March 2, 1918, p. 643; Reports Council Pharm.
& Chem., 1912, p. 47; 1915, p. 58.
Tongaline and Quinine Tablets (Mellier Drug Co.), The Journal,
July 17, 1915, p. 269.
Tongaline Tablets, 27
Tonga-Salicyl (H. K. Wampole & Co.), The Journal, May 10, 1913,
p. 1478; Reports Council Pharm. & Chem., 1912, p. 47.
Tonic Beef, S. & D. (Sharp & Dohme), The Journal, May 11, 1907,
p. 1612; Reports Council Pharm. & Chem., 1905-8, opp. p. 64;
Propaganda, ed. 9, p. 133.
Tonols (Schering’s Glycerophosphates), 94
Tonols (Schering’s Glycerophosphates), (Schering & Glatz, Inc.), The
Journal, Sept. 30, 1916, p. 1033; Reports Council Pharm. & Chem.,
1916, p. 34.
Toxicide, 307
Toxicide (Toxicide Laboratories, Chicago), The Journal, Oct. 8, 1921,
p. 1197; Reports Council Pharm. & Chem., 1921, p. 68.
Toxinol (Hughes Chemical Co.), The Journal, Dec. 2, 1916, p. 1687;
Reports Council Pharm. & Chem., 1912, p. 39; 1916, p. 38.
Trade Names, Patents perpetuated by, 544
Tri-Arsenole (Medical Supply Co.), Reports Council Pharm. & Chem.,
1917, p. 156.
Tri-Arsenole, L. O. Compound No. 1 and L. O. Compound No. 2, 163
Trifolium Compound, Extract (Wm. S. Merrell Chemical Co.), Reports
Council Pharm. & Chem., 1912, p. 39.
Trifolium Compound, Fluidextract (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 40.
Trifolium Compound, Syrup (Hance Bros. & White; Eli Lilly & Co.; H. K.
Mulford Co.; Parke, Davis & Co.; Ray Chemical Co.; F. Stearns
& Co.), Reports Council Pharm. & Chem., 1912, p. 39, 40.
Trifolium Compound with Cascara Syrup (Parke, Davis & Co.), Reports
Council Pharm. & Chem., 1912, p. 40.
Tri-Iodides (Henry) (Henry Pharmacal Co.), The Journal, Feb. 6, 1915,
p. 528; Reports Council Pharm. & Chem., 1915, p. 9; Reports Chem.
Lab., 1914, p. 65; Propaganda, ed. 9, p. 198.
Trilene Tablets, Reports Council Pharm. & Chem., 1912, p. 39.
Trimethol, 140
Trimethol (Thos. Leeming & Co.), The Journal, Aug. 11, 1917, p. 485;
Reports Council Pharm. & Chem., 1917, p. 43.
Triner’s American Elixir of Bitter Wine, 139
Triotonol Tablets, 94
Triotonol Tablets (Schering & Glatz, Inc.), The Journal, Sept. 30,
1916, p. 1033; Reports Council Pharm. & Chem., 1916, p. 34.
Triple Arsenates with Nuclein, 256
Triple Arsenates with Nuclein (Abbott Laboratories), Reports Council
Pharm. & Chem., 1919, p. 92.
Troches of Ammonium Chloride, druggists refuse to supply, 552
Trophenine (Reed & Carnrick Co.), The Journal, Oct. 5, 1907, p. 1198;
Reports Council Pharm. & Chem., 1905-8, p. 79.
Trypsogen (G. W. Carnrick Co.), The Journal, Nov. 1, 1913, p. 1649;
Propaganda, ed. 9, p. 403.
Tubercle Bacilli, Dixon’s Suspension of Dead, 158
Tubercle Bacilli Emulsion, Polygeneous (Farbwerke-Hoechst Co.),
Reports Council Pharm. & Chem., 1917, p. 146.
Tubercle Bacilli Extract, Dixon’s, 158
Tubercle Bacilli, Triturated (Farbwerke-Hoechst Co.), Reports Council
Pharm. & Chem., 1917, p. 146.
Tubercle Germs, Dried Dead (Farbwerke-Hoechst Co.), Reports Council
Pharm. & Chem., 1917, p. 146.
Tubercle Vaccine, Sherman’s Non-Virulent (G. H. Sherman) The Journal,
Nov. 21, 1914, p. 1870; Reports Council Pharm. & Chem., 1914,
p. 128.
Tuberculin, Bovine (Farbwerke-Hoechst Co.), Reports Council Pharm.
& Chem., 1917, p. 146.
Tuberculin, Bovine, T. R. (Farbwerke-Hoechst Co.), Reports Council
Pharm. & Chem., 1917, p. 146.
Tuberculin, “Koch” New (T. R.) (Farbwerke-Hoechst Co.), Reports
Council Pharm. & Chem., 1917, p. 146.
Tuberculin “Koch” (Old) (Farbwerke-Hoechst Co.), Reports Council
Pharm. & Chem., 1917, p. 146.
Tuberculin Old, Bovine (Farbwerke-Hoechst Co.), Reports Council Pharm.
& Chem., 1917, p. 146.
Tuberculin-Rosenbach (Kalle Color & Chemical Co.), Reports Council
Pharm. & Chem., 1917, p. 161.
Tuberculin Test Plate, Keller’s (A. H. Keller), The Journal, Dec. 19,
1914, p. 2250.
Tuberculin T. O. A. (Farbwerke-Hoechst Co.), Reports Council Pharm.
& Chem., 1917, p. 146.
Tuberculin, Vacuum (Farbwerke-Hoechst Co.), Reports Council Pharm.
& Chem., 1917, p. 146.
Tuberculin, Vacuum Bovine (Farbwerke-Hoechst Co.), Reports Council
Pharm. & Chem., 1917, p. 146.
Tuberculoids (Columbus Pharmacal Co.), The Journal, Feb. 22, 1908,
p. 704.
Tuberculosis-Diagnostic “Hoechst” (Farbwerke-Hoechst Co.), Reports
Council Pharm. & Chem., 1917, p. 146.
Tuberculosis-Diagnostic “Hoechst” Dry in Tubes (Farbwerke-Hoechst
Co.), Reports Council Pharm. & Chem., 1917, p. 146.
Tuberculosis-Diagnostic “Hoechst” (0.1 per cent.) Solution (Farbwerke-
Hoechst Co.), Reports Council Pharm. & Chem., 1917, p. 146.
Tuberculosis Serum Vaccine “Hoechst” (Farbwerke-Hoechst Co.), Reports
Council Pharm. & Chem., 1917, p. 161.
Tubo-Arg (Tubo Pharmacal Co.), Reports Council Pharm. & Chem., 1915,
p. 175.
Tumors and Chemotherapy, 499
Turkey Corn, Reports Council Pharm. & Chem., 1912, p. 47.
Tyree’s Antiseptic, 401
Tyree’s Antiseptic Powder, 462
Tyree’s Elixir of Buchu and Hyoscyamus Compound, 57
Ulax Salt (F. H. Strong Co.), Reports Council Pharm. & Chem., 1915,
p. 175.
Unctol, 166
Unctol (R. R. Rogers Chemical Co.), Reports Council Pharm. & Chem.,
1917, p. 162.
Unguentine (Norwich Pharmacal Co.), The Journal, March 27, 1909,
p. 1047; July 17, 1915, p. 272; Reports Chem. Lab., 1909, p. 21;
Propaganda, ed. 9, p. 254.
Unguentum Selenio Vanadic (v. Roemer) (A. von Roemer), The Journal,
Nov. 21, 1914, p. 1870; Reports Council Pharm. & Chem., 1914,
p. 129; Propaganda, ed. 9, p. 207.
Unicorn Root, The Journal, Jan. 22, 1910, p. 304; Reports Council
Pharm. & Chem., 1910, p. 10; Propaganda, ed. 9. p. 208.
Uranoblen (A. Grimme), Reports Council Pharm. & Chem., 1915, p. 176.
Urasol (Organic Chemical Mfg. Co.), The Journal, Sept. 5, 1908,
p. 818; May 8, 1909, p. 1511; Reports Council Pharm. & Chem.,
1905-8, p. 166; 1909, p. 64.
Urea, Hydrochlorid and Quinin, 467
Uricedin (Fischer Chemical Importing Co.), The Journal, Nov. 23,
1907, p. 1788; Reports Chem. Lab., 1909, p. 20; Propaganda, ed. 9,
p. 256.
Uricsol, 30
Uricsol (Uricsol Chemical Co.), The Journal, Aug. 14, 1915, p. 638;
Reports Council Pharm. & Chem., 1915, p. 149; Reports Chem. Lab.,
1915, p. 96.
“Uri-Na Test”, 498
Uriseptin (Gardner-Barada Chemical Co.), The Journal, Aug. 29, 1908,
p. 773; Reports Chem. Lab., to 1909, p. 40; Propaganda, ed. 9,
p. 256.
Urodonal, 32
Urodonal (Geo. J. Wallau, Inc.), The Journal, Aug. 14, 1915, p. 639;
Reports Council Pharm. & Chem., 1915, p. 153.
Uroluetic Test, Capell’s, 497
Uroluetic Test, Capell’s (Capell’s Laboratory), The Journal, Aug. 23,
1919, p. 626.
Uron (Uron Chemical Co.), The Journal, Nov. 3, 1906, p. 1500; Reports
Council Pharm. & Chem., 1905-8, p. 26.
Urotropin, 316
Urotropin a brand of hexamethylenamin, U. S. P., 318
Urotropin marketed under unwarranted therapeutic claims, 317
Uterine Sedative, Elixir (Eli Lilly & Co.), The Journal, Aug. 31,
1912, p. 735; Reports Council Pharm. & Chem., 1912, p. 44;
Propaganda, ed. 9, p. 410.
Uterine Tonic, Buckley (The Abbott Laboratories), Reports Council
Pharm. & Chem., 1912, p. 41.
Uterine Tonic, Girard (Girard Chemical Co.), Reports Council Pharm.
& Chem., 1912, p. 41.
Uterine Tonic (Parke, Davis & Co.), Reports Council Pharm. & Chem.,
1912, p. 46.
Uterine Tonic, Elixir (F. Stearns & Co.), Reports Council Pharm.
& Chem., 1912, p. 46.
Uterine Tonic (Tablet), (Maltbie Chemical Co.), Reports Council
Pharm. & Chem., 1912, p. 41.
Uterine Wafers, Micajah’s (Micajah & Co.), The Journal, March 26,
1910, p. 1070; Sept. 25, 1915, p. 1128; Reports Council Pharm.
& Chem., 1916, p. 66; Reports Chem. Lab., 1910, p. 18; 1915, p. 100;
Propaganda, ed. 9, p. 240.
Uterine Wafers, Naphey’s Medicated, 107
Utero Tonic (Nelson, Baker & Co.), Reports Council Pharm. & Chem.,
1912, p. 46.
Utros (H. K. Mulford Co.), Reports Council Pharm. & Chem., 1912,
p. 46.
Vaccine as a prophylactic in influenza, 572
Vaccine, B. Coli-Combined-Bacterin, 185
Vaccine, Catarrhal Vaccine Combined-Lilly, 187
Vaccine, Curative Vaccine, Bruschettini, 58
Vaccine, Friedmann’s (Standard Distributing Co.). Reports Council
Pharm. & Chem., 1914, p. 136.
Vaccine-Lilly, Influenza Mixed, 187
Vaccine, M. Catarrhalis-Combined-Bacterin, 184
Vaccine, Non-Virulent Tubercle Bacillus (G. H. Sherman).--
See Tubercle Vaccine, Sherman’s Non-Virulent.
Vaccine, No. 2 (Staph-Strep. Bacterin), Special Bacterial, 254
Vaccine No. 3 (Pneumo-Staph-Strep. Bacterin), Special Bacterial, 254
Vaccine No. 4 (Pneumo-Staph-Strep-Coli Bacterin), Special
Bacterial, 254
Vaccine No. 5 (Influenza Combined Bacterin), Special Bacterial, 254
Vaccine No. 11 (Pneumo-Strep. Bacterin), Special Bacterial, 254
Vaccine No. 15 (Combined Whooping Cough Bacterin), Special
Bacterial, 254
Vaccine No. 16 (Mixed Gonococcus Bacterin), Special Bacterial, 254
Vaccine, No. 40, Sherman’s Mixed, 188
Vaccine, Pertussis-Combined-Bacterin, 185
Vaccine, Streptococcus-Rheumaticus-Combined-Bacterin, 185
Vaccines-Abbott, Mixed, 184
Vaccines and Serums, 521
Vaccines for “Colds”, 573
“Vaccines” in toxic conditions, 560
Vaccines, Influenza, 520
Vaccines, Mixed, The Journal, June 22, 1918, p. 1967; Reports Council
Pharm. & Chem., 1918, p. 11. See also: B. Coli-Combined-Bacterin;
Catarrhal Vaccine-Combined-Lilly; Influenza Mixed Vaccine-Lilly;
Influenza Serobacterin Mixed-Mulford; M. Catarrhalis-Combined
Bacterin; Mixed Vaccine No. 40, Sherman’s; Pertussis-Combined-
Bacterin; Streptococcus-Rheumaticus-Combined-Bacterin;
Streptococcus-Viridans-Combined-Bacterin.
Vaccines, Several “Mixed”, 184
Van Horn and Sawtell--K-Y Lubricating Jelly, 147
Vanadic Acid, The Journal, May 9, 1908, p. 1548; July 24, 1909,
p. 309.
Vanadiol (Vanadium Chemical Co.), The Journal, Jan. 18, 1913,
p. 225; Reports Council Pharm. & Chem., 1913, p. 7; Propaganda,
ed. 9, p. 209.
Vanadioseptol (Vanadium Chemical Co.), The Journal, Jan. 18, 1913,
p. 225; Reports Council Pharm. & Chem., 1913, p. 7; Propaganda,
ed. 9, p. 209.
Vanadium, The Journal, June 3, 1911, p. 1648.
Vanadium Solution for Intravenous and Hypodermic Use (Vanadium
Chemical Co.), The Journal, Jan. 18, 1913, p. 225; Reports Council
Pharm. & Chem., 1913, p. 7; Propaganda ed. 9, p. 209.
Vanadoforms (Vanadium Chemical Co.), The Journal, Jan. 18, 1913,
p. 225; Reports Council Pharm. & Chem., 1913, p. 7; Propaganda,
ed. 9, p. 209.
Vapo-Cresolene (Vapo-Cresolene Co.), The Journal, April 4, 1908,
p. 1135; Reports Chem. Lab., to 1909, p. 65; Propaganda, ed. 9,
p. 408.
Vasogen (Lehn & Fink), The Journal, Feb. 13, 1909, p. 575; Propaganda,
ed. 9, p. 408.
Vass Chemical Company--Thialion, 470
V-E-M (Schoonmaker Laboratories, Inc.), 166
V-E-M Unguentum Eucalyptol Compound, 167
V-E-M Unguentum Eucalyptol Compound (Schoonmaker Laboratories, Inc.),
Reports Council Pharm. & Chem., 1917, p. 163.
V-E-M with Boric Acid, 167
V-E-M with Boric Acid (Schoonmaker Laboratories, Inc.), Reports
Council Pharm. & Chem., 1917, p. 163.
V-E-M with Camphor, 167
V-E-M with Camphor (Schoonmaker Laboratories, Inc.), Reports Council
Pharm. & Chem., 1917, p. 163.
V-E-M with Ichthyol, 167
V-E-M with Ichthyol (Schoonmaker Laboratories, Inc.), Reports Council
Pharm. & Chem., 1917, p. 163.
V-E-M with Stearate of Zinc, 167
V-E-M with Stearate of Zinc (Schoonmaker Laboratories, Inc.), Reports
Council Pharm. & Chem., 1917, p. 163.
Venarsen, 471
Venarsen (Intravenous Products Co.), The Journal, May 22, 1915,
p. 1780; March 25, 1916, p. 978; Reports Council Pharm. & Chem.,
1915, p. 52; Reports Chem. Lab., 1915, p. 82; Propaganda, ed. 9,
p. 212.
Vencalxodine (Intravenous Products Co.), The Journal, Feb. 16, 1918,
p. 481.
Venodine (Intravenous Products Co.). The Journal, June 26, 1915,
p. 2155; March 25, 1916, p. 278; Reports Council Pharm. & Chem.,
1915, p. 145; Propaganda, ed. 9, p. 214.
Venomer (Intravenous Products Co.), The Journal, March 25, 1916,
p. 978.
Venosal, 169, 435
Venosal (Intravenous Products Co.), The Journal, Jan. 5, 1918, p. 48;
Reports Council Pharm. & Chem., 1917, p. 118; Reports Chem. Lab.,
1917, p. 57.
Veracolate (Marcy Co.), The Journal, April 30, 1910, p. 1458; Aug. 1,
1914, p. 420; April 24, 1915, p. 1440; Reports Council Pharm.
& Chem., 1915, p. 141; Propaganda, ed. 9, pp. 216, 344.
Veracolate with Iron, Quinine and Strychnine (Marcy Co.), The Journal,
April 24, 1915, p. 1440; Reports Council Pharm. & Chem., 1915,
p. 141.
Veracolate with Pepsin and Pancreatin (Marcy Co.), The Journal,
April 24, 1915, p. 1440; Reports Council Pharm. & Chem., 1915,
p. 141.
Veroform Germicide (Veroform Hygienic Co.), The Journal, Nov. 22,
1913, p. 1920; Reports Council Pharm. & Chem., 1913, p. 29.
Veronal, 371
Veronal (Barbital), 370
Veronal-Sodium, 371
Viburn-Ovaro (Ray Chemical Co.), Reports Council Pharm. & Chem., 1912,
p. 46.
Viburnum Compound, Hayden’s (New York Pharmacal Co.), The Journal,
Aug. 31, 1912, p. 735; Jan. 23, 1915, p. 359; Reports Council Pharm.
& Chem., 1914, p. 95; Propaganda, ed. 9, pp. 218, 409.
Viburnum Compound, Elixir (Nelson, Baker & Co.), The Journal, Aug. 31,
1912, p. 735; Propaganda, ed. 9, p. 410.
Viburnum Compound (Tablets), (Parke, Davis & Co.), Reports Council
Pharm. & Chem., 1912, p. 41.
Viburnum Compound (Tablet) (Uterine Tonic), (Parke, Davis & Co.),
Reports Council Pharm. & Chem., 1912, p. 46.
Viburnum Compound (Tablet) (Smith, Kline & French Co.), Reports
Council Pharm. & Chem., 1912, p. 46.
Viburnum Sedative (Fraser Tablet Co.), Reports Council Pharm. & Chem.,
1912, p. 46.
Viburnumal (Louisville Pharmacal Works), The Journal, Aug. 31, 1912,
p. 735; Reports Council Pharm. & Chem., 1912, p. 44; Propaganda,
ed. 9, p. 410.
Vibutero (F. Stearns & Co.), The Journal, Aug. 31, 1912, p. 735;
Reports Council Pharm. & Chem., 1912, p. 46; Propaganda, ed. 9,
p. 410.
Vigoral (Armour & Co.), The Journal, Jan. 23, 1909, p. 311;
Propaganda, ed. 9, p. 472.
Vin Mariani (Mariani & Co.), The Journal, Nov. 24, 1906, p. 1751;
Reports Council Pharm. & Chem., 1905-8, p. 29; Propaganda, ed. 9,
p. 221.
Vinum Extract Morrhuae, Stearns, 59
Violet Ray Generator, Sterling, 572
Virol (Etna Chemical Co.), The Journal, Feb. 20, 1915, p. 683; Reports
Council Pharm. & Chem., 1915, p. 132; Propaganda, ed. 9, p. 225.
Vitamin B Concentrates and Yeast Preparations, 321
Vitamins: their distribution, 561
Vitaphos (The Grain Chemical Company, Inc.), Reports Council Pharm.
& Chem., 1921, p. 74.
Walker Pharmacal Company--Succus Cineraria Maritima, 455
Wallau, George J., Inc.--
Eumictine, 262
Filudine, 41
Jubol, 31
Sulfuryl Monal, 86
Urodonal, 32
Wampole, H. K., & Co.--Hypno-Bromic Compound, 430
Warming bottles, Sodium Acetate in, 329
Water, Buffalo Lithia Springs (Buffalo Lithia Springs Water Co.), The
Journal, Sept. 12, 1908, p. 931.
Water Eryngo, Reports Council Pharm. & Chem., 1912, p. 47.
Webster Co., William A. and the Direct Pharmaceutical Co., 564
Weeks Chemical Company--Chlorlyptus, 277
Westerfield’s Digitalis Tablets, 215
Wheeler’s Tissue Phosphates, 129, 463
White, G. S., and the Allied Medical Associations of America, 490
White, Mark, Goiter Serum Laboratories--Mark White Goiter Serum and
Mark White Iodinized Oil, 87
White Sulphur Salts (White Sulphur Springs, Inc.), The Journal,
Nov. 21, 1914, p. 1870; Reports Council Pharm. & Chem., 1914.
p. 128.
Whiteruss (Lubric Oil Co.), The Journal, July 10, 1915, p. 175.
Whooping Cough Bacterin, Combined, Special Bacterial Vaccine
No. 15, 254
Wild Indigo, The Journal, Jan. 22, 1910, p. 304; Reports Council
Pharm. & Chem., 1910, p. 19; Propaganda, ed. 9, p. 208.
Wild Yam, The Journal, Jan. 22, 1910, p. 304; Reports Council Pharm.
& Chem., 1910, p. 10; Propaganda, ed. 9, p. 208.
William F. Koch Cancer Remedy, 437
Williams, Henry Smith, and “Proteal Therapy”, 443, 494
Wine, Chapoteaut’s (E. Fougera & Co., Inc.), The Journal, Dec. 19,
1914, p. 2247; Reports Council Pharm. & Chem., 1914, p. 77;
Propaganda, ed. 9, p. 60.
Wine, Stearns’ (F. Stearns & Co.), Reports Council Pharm. & Chem.,
1915, p. 177.
Winslow Laboratory--Pineoleum advertising methods, 442
Winthrop Chemical Company, Inc.--
Elarson, 248
Helmitol, 295
Woolley, D. E., Manager of Cosmopolitan Cancer Research Society, 414
Worlds Wonder Remedy (W. W. Remedy Co., Superior, Wis.), Reports
Council Pharm. & Chem., 1918, p. 82.
Wulfing, A., Company--Formamint, 33
Wyeth, John, and Brother--
Hydras, 96
Robinol, 95
Xanol (Wm. S. Merrell Chemical Co.), Reports Council Pharm. & Chem.,
1911, p. 64.
Xeroform, 352
Xeroform-Heyden, 216, 349
Yarbrough, Charles C.--Biniodol, 121
Yeast, 566
Yeast Preparations and Vitamin B Concentrates, 321
Yerba Santa, Maltzyme with, 211
Yogurt (Yogurt Co.), The Journal, Jan. 30, 1909, pp. 372, 397.
Yohimbin Spiegel (Lehn & Fink), The Journal, March 30, 1907, p. 1127.
Zemacol (Norwich Pharmacal Co.), The Journal, May 14, 1910, p. 1626;
Reports Chem. Lab., 1910, p. 42; Propaganda, ed. 9, p. 259.
Ziratol, 148
Ziratol (Bristol-Myers Co.), The Journal, Oct. 6, 1917, p. 1191;
Reports Council Pharm. & Chem., 1917, p. 55; Reports Chem. Lab.,
1917, p. 51.
Zyme-oid (Oxychlorin Chemical Co.), The Journal, May 23, 1908,
p. 1706; Reports Chem. Lab., to 1909, p. 34; Propaganda, ed. 9,
p. 261.
Zymotoid, Arnold’s (Zymotoid Co.), The Journal, April 6, 1912,
p. 1030; Reports Chem. Lab., 1912, p. 68; Propaganda, ed. 9, p. 412.
Spelling variations:
amenorrhea/amenorrhoea
ampoule/ampule/ampul
anaemia/anemia
analgetic/analgesic
any one/anyone
arsenphenolamin/arseno-phenolamin
arsphenamin/arsphenamine
bromid/bromide
cerebral-spinal/cerebro-spinal/cerebrospinal
chlorid/chloride
cocain/cocaine
Cod-Liver Oil/Cod Liver Oil
diethylenediamene/diethylene-diamine
dioxid/dioxide
drams/drachms
dulness/dullness
envelop/envelope
every one/everyone
extention/extension
formaldehyd/formaldehyde
golden-seal/goldenseal
gonorrhoic/gonorrheaic
Grip/Grippe
guaranty/guarantee
Heitzman/Heitzmann
hexamethylenetetramin/hexamethylenetetramine/hexamethylene-tetramine/
hexamenthylenetetramin
iodid/iodide
iodin/iodine
melena/melaena
oxid/oxide
Parresine/Paresine
pharmacopeia/pharmacopoeia
post-graduate/postgraduate
sanatarium/sanitarium/sanatorium
selenio-vanadium/selenium-vanadium
sequelæ/sequelae/sequella
sulphurated/sulphureted/sulphuretted/sulphurretted
technique/technic
vitamines/vitamins
Spelling corrections:
accompanished —> accomplished
accurtely —> accurately
acethphenetidin —> acetphenetidin
advertiseing —> advertising
advertisments —> advertisements
aluminium —> aluminum
Amercan —> American
amples —> ampules
an ypure —> any pure
and —> an
and —> on
Anelgesic —> Analgesic
anitseptic —> antiseptic
anodoyne —> anodyne
anohter —> another
aortis —> aortitis
artifically —> artificially
asosciated —> associated
Assimiliation —> Assimilation
at —> as
atttention —> attention
authenic —> authentic
author —> authors
Bacilus —> Bacillus
baillus —> bacillus
Barbitol —> Barbital
beeen —> been
benefical —> beneficial
betanaphtol —> betanaphthol
betwen —> between
bibliograpy —> bibliography
Binghampton —> Binghamton
binodide —> biniodide
Botazzi —> Bottazzi
carbonic —> carbolic
carodylate —> cacodylate
carrer —> carrier
carthartic —> cathartic
characteristc —> characteristic
Chautaqua —> Chautauqua
chefly —> chiefly
Chemisty —> Chemistry
Chlorilyptus —> Chlorlyptus
Choron —> Chloron
cities —> cites
claims —> claim
clipping —> clippings
clorless —> colorless
coeffiecient —> coefficient
Collosal —> Collosol
compained —> complained
compaint —> complaint
compatable —> compatible
Compond —> Compound
compostion —> composition
Concernng —> Concerning
conditons —> conditions
conection —> connection
coneentrated —> concentrated
confréres —> confrères
connenction —> connection
constitutent(s) —> constituent(s)
Contro —> Control
convicition —> conviction
corespondence —> correspondence
corpuscules —> corpuscles
crystaline —> crystalline
davantages —> advantages
deparment —> department
destroyes —> destroys
develope —> develop
diehylbarbituric —> diethylbarbituric
Diethylbarbiutric —> Diethylbarbituric
digtalis —> digitalis
dirctory —> directory
distate —> distaste
distils —> distills
does —> doses
dulness —> dullness
dystentery —> dysentery
Ehlrich —> Ehrlich
Electobioscope —> Electrobioscope
emipric —> empiric
employe —> employee
entiled —> entitled
eperiments —> experiments
esesntially —> essentially
essentally —> essentially
eucalytpus —> eucalyptus
examation —> examination
extravant —> extravagant
exurberant —> exuberant
Farbkerke-Hoechst —> Farbwerke-Hoechst
Farbwercke-Hoechst —> Farbwerke-Hoechst
Farbwerke-Hochest —> Farbwerke-Hoechst
Farbwerke-Hoechest —> Farbwerke-Hoechst
Farkwerke —> Farbwerke
Ferbwerke —> Farbwerke
finsh —> finish
Firwin —> Firwein
fitrate —> filtrate
flgrant —> flagrant
fluorish —> flourish
FOM —> FROM
form —> from
fradulent —> fraudulent
Fritsche —> Fritzsche
gactric —> gastric
galactogogic —> galactagogic
galactogogue —> galactagogue
Galatagogue —> Galactagogue
Giesecke —> Gieseke
Glyecrin —> Glycerin
Goering —> Goehring
gonoccoccus —> gonococcus
gualtheria —> gaultheria
guiacol —> guaiacol
habtual —> habitual
Hallon —> Hallion
Hcl —> HCl
he —> be
Heath —> Health
hexamenthylenamin —> hexamethylenamin
Hexamenthylenetetramin —> Hexamethylenetetramin
Hexamethylentetramine —> Hexamethylenetetramine
Higienic —> Hygienic
hundrance —> hundrance
Hussy —> Hussey
hydiodic —> hydriodic
hydochloric —> hydrochloric
hyerplastic —> hyerplastic
hyocyamus —> hyocyamus
hyoscymus —> hyoscymus
idodin —> iodin
idosyncrasy —> idiosyncrasy
inections —> injections
ingorance —> ignorance
insommia —> insomnia
intractions —> interactions
intramuscuarly —> intramuscularly
itme —> time
jubject —> subject
lechithin —> lecithin
liklihood —> likelihood
lisited —> listed
LYPMH —> LYMPH
Maganese —> Manganese
Magnesim —> Magnesium
manufacturer —> manufacturers
Mazazine —> Magazine
mecurial —> mercurial
mecuric —> mercuric
medicince —> medicine
Metorrhagia —> Metrorrhagia
Meyers —> Myers
minimum —> minim
mixutre —> mixture
monoceticacidester —> monoaceticacidester
monoply —> monopoly
Naphtol —> Naphthol
napthal —> napthol
Napthol —> Naphthol
neuralga —> neuralgia
nirtic —> nitric
Nutrolactic —> Nutrolactis
O. H. —> A. H.
odide —> iodide
Ophtalmol —> Ophthalmol
or —> of
orginal —> original
pag —> page
pamphet —> pamphlet
parffin —> paraffin
parminobenzoate —> paraminobenzoate
particuarly —> particularly
pasticity —> plasticity
patent —> patient
pharmaceptical —> pharmaceutical
Pharmacopia —> Pharmacopeia
pharmactists —> pharmactists
pharmceutical —> pharmaceutical
phoshite —> phosphite
Phram. —> Pharm.
physicial —> physical
Pineolum —> Pineoleum
Pinoleum —> Pineoleum
Pitsburgh —> Pittsburgh
pituiary —> pituitary
Plurig andular —> Pluriglandular
Pneumocci —> Pneumococci
Pneumococccus —> Pneumococcus
pnuemonia —> pneumonia
popularily —> popularly
populary —> popularly
postive —> positive
Power —> Powder
precipiate —> precipitate
prefare —> preface
preparatons —> preparations
prescibed —> prescribed
prevous —> previous
prinicple —> principle
procedues —> procedures
profesion —> profession
proper ties —> properties
proponderant —> preponderant
Protier —> Portier
Protogen —> Proteogen
puporting —> purporting
pyrogenic —> pyogenic
qestions —> questions
quantiatively —> quantitatively
Querry —> Query
Quine —> Quinine
radicle —> radical
Rathjen —> Rahtjen
recomendation —> recommendation
recommmend —> recommend
recommmended —> recommended
refree —> referee
rememebered —> remembered
Reparts —> Reports
ressistance —> resistance
restrospect —> retrospect
reults —> results
Rhatjen —> Rahtjen
saccarine —> saccharine
same —> some
santorium —> sanatorium
scientfic —> scientific
seleninum —> selenium
seleno-vanadium —> selenio-vanadium
series —> serious
Shering —> Schering
simiplicity —> simplicity
specifially —> specifically
Staphylococus —> Staphylococcus
submited —> submitted
submittted —> submitted
substaneous —> subcutaneous
supernatent —> supernatant
suport —> support
syphilus —> syphilis
Syracue —> Syracuse
teasponful —> teaspoonful
tehnic —> technic
tetraoidid —> tetraiodid
that —> than
thearapeutic —> therapeutic
thiomethylarsniate —> thiomethylarsinate
Thyroidectin —> Thyroidectin
tisssues —> tissues
tisues —> tissues
to —> too
travenous —> intravenous
treament —> treatment
tremely —> extremely
troat —> throat
tubercuclosis —> tuberculosis
unbeliveable —> unbelievable
vasty —> vastly
vially —> vitally
Wulflng —> Wulfing
240:2'1, 1887. —> 240:291, 1887.
*** End of this LibraryBlog Digital Book "The Propaganda for Reform in Proprietary Medicines, Vol. 2 of 2" ***
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