Chapter XVIII: Introduction: The Council on Pharmacy and Chemistry was established (11)

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.

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.)

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.

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.