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.