Chapter IX: Part I: Council Reports (4)

[37] Teichmann: Therap. d. Gegenw., 1907, xlviii, 199.

Eggleston and Hatcher[38] compared the emetic and cardiac activity
of Digalen and numerous other digitalis bodies and preparations and
found that the emetic activity of Digalen was decidedly greater in
proportion to its cardiac (or therapeutic) action than was that of
digitalis or digitoxin.

[38] Eggleston, Cary, and Hatcher, Robert, A.: The Emetic Action of
the Digitalis Bodies, The Journal A. M. A., Feb. 15, 1913, p. 499.

In the absence of any evidence to controvert this clinical and
experimental evidence, the continued claim that Digalen does not
disturb the stomach must be looked on as deliberate misrepresentation.

MISLEADING THERAPEUTIC CLAIMS

The recommendation that Digalen be dismissed from N. N. R. is made
with the full appreciation of the fact that the manufacturers of
Digalen and their agents have repeatedly stated that they desired to
comply with the rules of the Council, and that they have withdrawn
several statements to which the Council has taken exception, but
the fact remains that despite these reiterations the advertisements
of Digalen continue to embody statements which the Council can only
consider misleading.

The Council believes that the following advertisements constitute
gross therapeutic exaggerations:

“Digalen a sheet anchor in pneumonia; a strong support to the heart
in this deadliest of infectious diseases among adults. The prompt
action of Digalen, by intravenous or intramuscular injection makes
it possible to save lives which might be otherwise hopelessly
lost. The best digitalis preparation which we have at the present
time.”[39]

[39] Advertisement in Am. Med., January and February, 1913.

“_The_ digitalis for children. Because its dosage can be
controlled. Endorsed by pediatrists everywhere.”[40]

[40] Advertisement in Merck’s Arch., April, 1913.

“The myocarditis of Tuberculosis so frequently encountered,
especially in the advanced stage of the disease, may be controlled
with the aid of Digalen. The standard digitalis preparation.”[41]

[41] South. Medical Journal, January to May, 1913, inclusive.

“Digalen is Absolutely _Reliable_. It is _standardized_ and
consequently _always uniform_. It _does not produce gastric
disturbances._”[42]

[42] Advertisement in Brit. Med. Jour., April 26, 1913.

Digalen is not a sheet anchor in pneumonia, for there is no drug deserving such a title. Digalen has no action which other digitalis preparations lack, and cannot save lives otherwise hopelessly lost. The dosage of Digalen cannot be controlled any better than that of other digitalis preparations, since its activity is variable. We cannot control the myocarditis of advanced tuberculosis by this or any other means.

CLAIMED SUPERIORITY

Various digitalis principles, including digitoxin, digitalin (true)
and digitalein, have been known for many years. Therapeutically they
have been found wanting and there appears to be no basis for the
continued claim that Digalen has any superiority over these several
digitalis principles. On the contrary, the evidence is accumulating
that Digalen has no advantage in any particular over a solution of
digitalein, and misleading claims of the manufacturers and their
agents certainly interfere with the formation of that calm and
unbiased opinion on the part of the general practitioner, which, when
applied to the non-proprietary digitalis principles has caused them
to fall into disuse.--(_From The Journal A. M. A., Sept. 5, 1914._)

DIORADIN REFUSED RECOGNITION

Report of the Council on Pharmacy and Chemistry

A preparation called Dioradin was placed on the market as a cure for consumption three years ago in Europe and somewhat later in this country. It was first submitted to the Council in July, 1911. Because of the manifestly unwarranted claims made for its use in the treatment of tuberculosis, the Council voted that the product be refused recognition for conflict with Rule 8, without at that time taking under consideration the question whether or not it was in conflict with other rules of the Council.

In June, 1912, further consideration of Dioradin was requested. The American agent having promised a reform in the methods of advertising, the Council considered the available evidence regarding the identity and value of the preparation. Examination of evidence regarding the composition of Dioradin--claimed to consist of radium chlorid, iodoform and menthol in an ether-oil solution--showed serious discrepancies as to the amount of radium as well as to the identity and amounts of other constituents. It was further found that the experimental evidence was insufficient and biased. Then, too, in view of the difficulty of judging the effects of medicines in tuberculosis, the clinical data were unconvincing. There was nothing to prove that the reported improvements, even if they actually occurred, were to be ascribed to the mixture as a whole rather than to any one of its constituents.

As a result of these findings, the Council voted that Dioradin be refused recognition and that the publication of these facts be authorized. In accordance with its regular procedure, it also submitted the report to the agent. In reply the agent submitted evidence which showed that he was not responsible for the misstatements about Dioradin but offered no facts that affected the Council’s findings.

The entire matter having been referred to a second referee, minor modifications of the first draft of the report were authorized. Since then the Dioradin Company has submitted two reports of examinations of Dioradin made for the company in Germany showing a higher radium content than that previously found. These reports do not alter the facts brought out in the report of the Council that the composition of Dioradin has been variable, which past variability arouses a feeling of uncertainty or lack of confidence. In view of this the amended report was ordered published and appears below.

W. A. Puckner, Secretary.

_FIRST SUBMISSION OF DIORADIN_

Dioradin, a preparation for the treatment of consumption originated
by Dr. R. de Szendeffy, Budapest, Hungary, was submitted to the
Council by Louis Gero, Ltd., New York, with the following statement
of composition:

“A radio-active preparation of Menthol, Iodin and Radium Barium
Chlorid 1/10 of a drop; in ether solution.”

A circular which accompanied the submission stated:

“Preparation No. 3 of Dioradin contains not only terpins but also
iodin salts.... In view of the fact that emanations of the radium
as well as the combinations of the evasive iodin terpins enter into
the organism through the lung....”

Later these indefinite statements of composition were supplemented by the following:

“In 100 c.c. there are:

1 gr. Iodoform.
5 " Menthol.
10 drops Radium chlorid solution
(1 milligr. in 100 c.c. of water).
5 gr. ether.
90 " Oil (ol. amygd. frig. press).”

In a circular contained in the package these claims were made:

“The preparations of the Dioradin are based on the miraculous
effects which scientific researches have shown in regard to the
different sicknesses treated with radium.

“It is generally known that radium, even if externally employed,
has proved itself to be a bactericidal remedy. Its effect is
multiplied if one employs it internally even in infinitesimal
doses, in consequence of its permanent action of emanation on the
organism.

“The preparations of the Dioradin contain the radium itself. For
this reason their antiseptic and bactericidal effect is much more
intensive than with medicaments which contain only its emanation,
which disappears in a short time.”

In view of the general extravagance of the claims made for its therapeutic action the preparation was rejected without considering other possible conflicts with the rules of the Council.

_SECOND SUBMISSION OF DIORADIN_

Having been advised of the rejection by the Council of Dioradin the
American agency, which in the meantime had become the Dioradin Co.,
requested further consideration. The Council therefore took up the
subject again. After certain typographical errors had been corrected
the following was now given as the composition:

“1 gram Iodoform.
5 grams Menthol.
10 drops Radium Chlorid Solution (containing 1 milligram of
radium chlorid in 100 cubic centimeters of water).
5 grams Ether.
89 grams expressed oil of almond.
This liquid is put up in ampules containing one cubic
centimeter of liquid.”

In support of the therapeutic claims for Dioradin the American agent
submitted literature consisting chiefly of articles by Dr. Bernheim
of Paris. Before reporting on the requested reconsideration of
Dioradin the referee directed the secretary of the Council to point
out to the American agent that in the formula given, the amount
of non-volatile matter should be about 90 per cent., whereas the
report of the Lederle Laboratories which accompanied the request for
reconsideration states that but 72.08 per cent. was found in the
analysis. In reply the agent stated that he had called the attention
of Dr. Szendeffy (the originator of Dioradin) to the discrepancies
concerning non-volatile matter and that he felt sure the discrepancy
was wholly accidental (_sic_). In a later communication the agent
submitted a statement of analysis from the Lederle Laboratories
of a new specimen of Dioradin according to which the amount of
non-volatile matter agreed essentially with the amount claimed by the
agent.

The referee, having examined the evidence, is of the opinion that
the statement of composition is misleading and that the therapeutic
claims are unwarranted, thus:

DISCREPANCIES IN RADIUM CONTENT

The chief claims for its therapeutic value are based on the radium
content, yet the discrepancies and contradictions, regarding this are
serious.

In connection with the reconsideration of this product the agent
presented a certificate of chemical examination by the Lederle
Laboratories in which the following statement was made as to the
radio-activity:

“Examination shows the preparation to possess slight radioactivity,
corresponding in activity to less than 1-10,000 of 1 milligram
of radium bromid per ampule. According to the sworn statement of
Dr. A. de Szendeffy, the originator of Dioradin, the preparation
contains 10 drops of radium chlorid solution (1 milligram in
100 cubic centimeters of water) in 100 cubic centimeters of the
preparation. This would correspond to 5-1,000 milligram of radium
chlorid in 100 cubic centimeters, or about 1-20,000 of 1 milligram
per ampule.”

A cursory reading of this paragraph gives the impression that Dioradin possesses fully the amount of radio-activity claimed by its originator, Dr. A. de Szendeffy. This impression is greatly strengthened by the concluding paragraph of the Lederle report, which says:

“In conclusion, our examination shows that the preparation
submitted to us as Dioradin possesses radio-activity, and contains
a fixed oil (apparently expressed oil of almond), iodoform, menthol
and ether, thus confirming the sworn statement of Dr. A. de
Szendeffy in regard to the composition of this product.”

On inquiry as to the method used by the Lederle Laboratories, in determining radio-activity the agent submitted a further statement of the Lederle Laboratories which describes the gamma ray test by which the determination was made and a radium value equivalent to 0.000041 mg. of radium bromid per capsule was obtained. The report then says:

“The variations of the single measurements from the mean in the
case of the natural leak and the leak with the Dioradin near were
so large that we did not feel justified in assigning much accuracy
to the figure, 0.000041, but stated that the amount of radium per
capsule could not be greater than 0.0001 mg., with the possibility
of there being a much smaller amount present.”

It is evident that the wording of the reports of the Lederle Laboratories is liable to give the impression that their examination confirms the claims made for Dioradin.

It is further evident from these reports that the amount of radio-active matter has not been definitely ascertained but that it is at the best very small. The unreliability of the claims for radium content of Dioradin was recently shown by Buechner,[43] who found a specimen obtained from an apothecary to contain but 1-1,000 of the amount claimed.

[43] Buechner: Pharm. Weekblad, March 2, 1912, p. 161.

VOLATILE AND NON-VOLATILE MATTER

The varying claims regarding the content of volatile and non-volatile
matter throw doubt on the entire composition of Dioradin, for if the
statement as to these is wrong the rest of the statement regarding
composition cannot be given credence.

In the first submission of Dioradin about 89 per cent. of
non-volatile matter was claimed but in the report of the analysis by
the Lederle Laboratories, which accompanied the resubmission, only
about 72 per cent. was found. Later the Lederle Laboratories reported
that an examination of a new specimen of Dioradin had shown about
90 per cent. of non-volatile matter. The discrepancies between the
composition claimed for Dioradin and that found for the product in
the first Lederle report has shown that the agent was quite ignorant
of the composition of the product which he was selling.

INDEFINITENESS OF THE IODIN CONTENT

The label on the trade package of Dioradin first submitted to the
Council stated that the product contained iodoform; a similar
statement was made in the submission of the product; the circular
accompanying the first submission stated that “iodin salts” were
contained in the product while the iodin content was referred to
further on in this circular as “combinations of evasive iodin
terpins.” In Bernheim’s papers, which have been used to advertise
Dioradin, and which are referred to in the same circular, the iodin
compound is called “iode peptonisé,” which, according to information
stated by the American agent to have come from Budapest, is to be
translated “iodized peptone.” What is the meaning of this confusion?
One would naturally suppose that the preparation to be sold in this
country contains iodoform in an ether-oil solution while the one used
by Bernheim and Dieupart[44] was stated to contain an _ethereal_
solution of “iodized peptone.” This is another mystification, for
an ethereal solution of any kind of peptone would be a novelty. The
matter is of some importance, for Bernheim and Dieupart lay great
stress on the difference between “peptonized iodin” and other iodin
(loc. cit., p. 333) and of the superiority of ethereal over oily
solutions (loc. cit., p. 334). The American agents, however, in
the second submission, state that this is all a mistake; that the
Dioradin used by Bernheim is the same Dioradin which was submitted to
the Council; and that this does not contain, and never did contain,
the ethereal solution of “iode peptonisé” to which Bernheim attached
so great importance. Bernheim (report to Medical Congress of Lyons)
himself has come to the same conclusion; for five months after his
first paper he believes that the “special salt of radium” (_sic_)
is the principal agent; so that the “peptonized iodin” must be
unimportant, and in a cablegram of July 4, 1912, he now informs
the Dioradin Company that the formula was incorrectly given in his
first papers “owing to my ignorance of actual composition,” and that
all the Dioradin used by him was of the composition stated in the
submission to the Council.

[44] Bernheim and Dieupart: Revue Internationale de la Tuberculose, May, 1911, p. 336.

While this vindicates the good faith of the American Dioradin
Company, it does not clear up the mystery. The question occurs at
once: What led Dr. Bernheim to make such positive statements? Was he
drawing purely on his imagination? If so, why did his imagination
take this peculiar special direction? Or if he did have some reason
to imagine the “iode peptonisé,” who supplied this reason? And if,
at that time, he was given to understand by Szendeffy, who must
have supplied him with the material, that it contained the iodized
peptone, how can he be positive at this time, that it did not contain
it? Has he actually analyzed the old material?

There is also a further question which needs to be answered. Why
has Dr. Szendeffy waited until Dioradin was rejected by the Council
before correcting Bernheim’s serious misapprehension, in the meantime
permitting the circulation of Bernheim’s paper?

Until these questions have been satisfactorily answered, the element
of mystery about the composition of Dioradin cannot be cleared away.

EXPERIMENTAL EVIDENCE

The available experimental evidence regarding “Dioradin” is
restricted to some quotations from its inventor Szendeffy, in the
paper of Bernheim and Dieupart (p. 334). These, if confirmed,
would show that radium alone has practically no effect on cultures
of tubercle or colon bacilli; that 0.1 gm. of “iode-menthol”
(concentration not stated) checks the growth of the acid-fast
organisms; and that this antiseptic efficiency can be nearly doubled
by the addition of a little radium. No quantitative data are given,
so that it is difficult to judge the accuracy of the observation.
Granting that it is correct, it would have little bearing on the
therapeutic actions of Dioradin, for there is nothing to show that
the effective test-tube concentration is reached in the pulmonary
tissues.

It is also claimed that the injection of Dioradin prevents tubercle
infection. The referee believes that the Council and the medical
profession should hesitate to accept this conclusion without further
details; and these would require confirmation by unprejudiced
observers.

CLINICAL EVIDENCE

The Dioradin Company submits considerable clinical data in favor of
Dioradin. It must be remembered that most favorable opinions have
been published, from time to time, about scores of “consumption
cures,” which have mysteriously lost their efficiency when their
novelty wore away. There is no more reason to doubt the good faith
of those who are enthusiastic about Dioradin than of those who have
been enthusiastic about other “cures.” There appear to be features
in the course of tuberculosis which make the judgment of therapeutic
measures peculiarly difficult. It is possible that impartial
clinical trials of Dioradin by tuberculosis experts appointed by the
Council might facilitate judgment as to the actual efficiency of
Dioradin. The referee doubts, however, whether this would advance the
Council very much toward the acceptance of the substance. Such an
investigation would be so lengthy that it should not be undertaken
until the Dioradin Company itself has offered at least presumptive
evidence in this direction, especially in view of the adverse report
recently made by Cecil Wall.[45] Ten tuberculous patients were
treated by Wall in strict accordance with the method outlined to
him by Bernheim, yet Wall concludes that none of the cases, though
treated accurately in accordance with the instructions, can be quoted
to justify any of the claims for the therapeutic efficiency of
Dioradin. The Council cannot undertake lengthy investigations of this
character until it is put in possession of data which would show to
its satisfaction that such investigations would probably be fruitful.

[45] Wall, C.: Brit. Med. Jour., July 20, 1912, p. 109.

CONCLUSIONS

From investigations made, it appears that the claims in regard to
the composition of Dioradin have contained vague statements and
contradictions which arouse a feeling of uncertainty and lack of
confidence. Until this uncertainty is cleared away, Dioradin cannot
be considered as complying with Rule 1. The experimental data are
insufficient and unconvincing. Some favorable clinical reports
have been submitted, but the accuracy of the observations is to be
questioned and they are more than offset by the negative results
observed by Cecil Wall. As might be expected, other negative results,
if observed, have not been submitted and there is nothing in the
manufacturer’s claim to show whether the improvement reported is
really due to the peculiar mixture called Dioradin or to any one of
its ingredients.

It is therefore recommended that Dioradin be not accepted for New and
Nonofficial Remedies. In view of the extensive advertising of this
preparation and because of the admittedly incorrect statements in the
earlier papers it is recommended that publication of this report be
authorized.--(_From The Journal A. M. A., Oct. 26, 1912._)

ECHINACEA

Report of the Council on Pharmacy and Chemistry

The Council has voted to reject several non-proprietary articles and has recommended that the reasons for their rejection be given in The Journal; among these is echinacea. The following paper has been submitted by a subcommittee with the recommendation that it be published. This recommendation was adopted.

W. A. Puckner, Secretary.

Echinacea

When this drug was first introduced, it was a typical nostrum, with exaggerations regarding its therapeutic value that were somewhat more gross than usual. It was later adopted by the eclectic school without being freed from the stigmata of its origin. It was also pressed into use as the main ingredient of such proprietary preparations as Echafolta, Ecthol Eusoma, etc. Efforts have been made to get the regular profession to use it in these various forms.

According to J. U. Lloyd (_Pharm. Review_, vol. xxii, p. 9-14), the introduction of echinacea into eclectic medicine is due to the efforts of Dr. H. F. C. Meyer to increase the sale of Meyer’s Blood Purifier, a secret remedy containing it. The following is a literal copy of the label on this nostrum:

+------------------------------------------------------------+
| MEYER’S BLOOD PURIFIER |
| DIRECTIONS |
| This is a powerful drug as an Alterative and Antiseptic |
| cases: _Rheumatism, Sick Headache, Erysipelas, Dyspepsia, |
| Old Sores and Biles, Open Wounds, Dizziness, Scrofula and |
| Sore Eyes._ |
| |
| In case of _Poisoning by Herbs, & C._, take the double |
| dosis, and _Bites of Rattlesnakes_ take three ounces three |
| times a day, until the swelling is gone. This is an |
| absolute cure within 24 hours. |
+------------------------------------------------------------+

After Lloyd had identified the plant, Meyer put the preparation out under another form with the following label:

+--------------------------------------------------------------+
| ECHINACEA ANGUSTEFOLIA |
| This is a powerful drug as an Alterative and Antiseptic |
| in all tumorous and Syphilitic indications; old chronic |
| wounds, such as fever sores, old ulcers, Carbuncles, Piles, |
| eczema, wet or dry, can be cured quick and active; also |
| Erysipelas. It will not fail in Gangrene. In fever it is a |
| specific; typhoid can be adverted in two to three days; also |
| in Malaria, Malignant, Remittent and Mountain fever it is a |
| specific. It relieves pain, swelling and inflammation, by |
| local use, internal and external. It has not and will not |
| fail to cure Diphtheria quick. It cures bites from the bee |
| to the rattlesnake, it is a specific. Has been tested in |
| more than fifty cases of mad dog bites in human and in every |
| case it prevented hydrophobia. It has cured hydrophobia. It |
| is perfectly harmless, internal and external. |
| |
| Dose.--One half to one fluid-drachm 3 or 4 times a day. |
| |
| Manufactured by H. C. F. Meyer, M.D. |
| Price, $ Pawnee City, Neb., U. S. A. |
| Patent |
+--------------------------------------------------------------+

These absurd claims of an evidently ignorant man have passed into the more recent proprietary advertising matters and into much of the eclectic writings. Indeed, the seemingly impossible had been attained by even surpassing Meyer’s all-but-all-embracing claims. Not content with endorsing echinacea as a positive and speedy “specific” for rattlesnake bite, syphilis, typhoid fever, malaria, diphtheria and hydrophobia, later enthusiasts have credited it with equally certain curative effects in tuberculosis, tetanus and exophthalmic goiter, and with the power of retarding the development of cancer.

It is worth noticing--although it is not surprising--that these far-reaching claims have been made on no better basis than that of clinical trials by unknown men who have not otherwise achieved any general reputation as acute, discriminating and reliable observers. No attempt seems to have been made to verify these claims by accurate scientific methods, clinical or otherwise, although this could very easily have been done.

Not one of the eulogistic reporters and exploiters seems to have considered it worth while to determine by the simplest control experiments whether the drug possesses any bactericidal or antiseptic powers whatever. It is therefore not very strange that discriminating physicians have failed to show much enthusiasm. One of the warmest endorsers of echinacea, C. S. Chamberlain (who later became the president of the Eusoma Pharmaceutical Company), complains that he has been unable to interest regular physicians in the remedy. He reviews the statements of previous authors and reports eight cases of infection, only two being acute or extensive, in which he used it with asserted success.

In view of the lack of any scientific scrutiny of the claims made for it, echinacea is deemed unworthy of further consideration until more reliable evidence is presented in its favor.

REFERENCES

Meyer, H. F. C.: _Eclectic Med. Jour._, 1887; Goss: _Chicago Med.
Times_, 1888; Hages: _Eclectic Med. Jour._, 1888; Shelly: _Medical
Gleaner_, 1894; Lloyd, C. G.: _Eclectic Med. Jour._, 1897; Lloyd,
J. U.: _Eclectic Med. Jour._, 1897; Lloyd, J. U.: _Pharm. Review_,
xxii, 9-14; Schnitz, Elsie M.: _Wis. Med. Recorder_, 1898, ii, 202;
White, J. N.: _Texas Med. News_, 1898, viii, 110-113; Stinson,
J. C.: Therap. _Gazette_, 1900; Hale, E.: _Lancet-Clinic_, March,
1901; Thielen, B. F.: Echafolta, Its Uses in Dental Surgery, _Dental
Reg._, 1903, vii, 462-465; Gorse, C. A.: _New Albany Med. Herald_,
1903-4, xxii, 384; Chamberlain, C. S.: _Louisville Monthly Jour.
Med. & Surg._, 1904-5, xi, 219-223; _Lancet-Clinic_, 1905, M. S.,
liv, 279-283; Ellingwood, F.: _Therap. Gazette_, 1905, 3, S., xxi,
298-300; French, J. M.: _Med. Brief_, 1905, xxxiii, 537; Mathews,
A. B.: _Georgia Pract._, 1905, i, 137-140.--(_From The Journal
A. M. A., Nov. 27, 1909._)

ECHTISIA, ECTHOL AND ECHITONE

Report of the Council on Pharmacy and Chemistry

Echtisia (Wm. S. Merrell Chemical Co.), Ecthol (Battle and Co.) and Echitone (Strong, Cobb and Co.) are proprietary preparations each of which is alleged to contain echinacea as its chief constituent. In 1909 the Council examined into the claims made for echinacea. This drug has been claimed to be a “specific” for rattlesnake bite, syphilis, typhoid fever, malaria, diphtheria and hydrophobia. Enthusiasts have credited it with equally certain curative effects in tuberculosis, tetanus, and exophthalmic goiter and with power of retarding the development of cancer. Of course there is no reliable or trustworthy evidence to substantiate these claims. Echinacea is not often prescribed under its own name, but is employed as an ingredient in proprietary preparations mixed with other little-used or obsolete substances. Thus Echtisia is said to contain echinacea, wild indigo, arbor vitae and poke root; Ecthol, to have echinacea and arbor vitae; Echitone, to consist of echinacea, pansy and blue flag. Naturally the manufacturers of such proprietaries make use of all available optimistic reports in promoting their sale, while each manufacturer ascribes special and peculiar virtues to the combination represented in his particular preparation. The Merrell Chemical Company claims that baptisia (wild indigo) is a “destroyer” of devitalizing elements in the blood “a vitalizer of the blood as well”; that thuja (arbor vitae) is a “perfect antiseptic and a generator of vital force in disorganized tissues,” and that a long list of diseases, including diphtheria, syphilitic sciatica and gonorrheal rheumatism, “are all more or less amenable to full doses” of phytolacca (poke root). Strong, Cobb and Co. maintain that Iris versicolor (blue flag) is “one of the most powerful excitants of the biliary, salivary and pancreatic secretions,” and that the “principal sphere of action of Viola tricolor [pansy] is in the gastro-intestinal canal and the skin.”

There is no satisfactory evidence that the claims for any of these substances are any more reliable than those for echinacea. Notwithstanding, Strong, Cobb and Co. claim for Echitone “not only the virtues of its constituent parts, but a wider field and a particular therapeutic value of its own”; Battle and Co., maintain that Ecthol is the “‘Ideal Corrector’ of depraved conditions of the fluids and tissues,” while the Merrell Company urges the virtues of Echtisia in a list of diseases ranging from acne to appendicitis and from gangrene to rattlesnake bite. The Council refused recognition to these three products and directed publication of reports to call attention to the exaggerated, unwarranted and often utterly absurd claims made for these and similar preparations.--(_From The Journal A. M. A., Jan. 2, 1915._)

ERGOAPIOL[N]

Abstract of Report of the Council on Pharmacy and Chemistry

[N] For abstract of report on a similar mixture, see Apergols, p. 26; for unabridged report of the Council’s action on Apergols and Ergoapiol see Reports Council Pharm. and Chem., 1914, p. 64.

Ergoapiol (Martin H. Smith Co., New York) is a mixture put up in capsules, each of which is said to contain

Apiol (Special M. H. S.) 5 grains
Ergotin 1 grain
Oil Savin 1/2 grain
Aloin 1/8 grain

Examination discloses the fact that, contrary to the claim made, each capsule, instead of containing 5 grains of apiol, really contains some liquid preparation of the type of oleoresin of parsley seed. Ergoapiol is recommended (on the label) for such diseases as “Amenorrhea, Dysmenorrhea and other Menstrual Disorders,” while a circular enclosed in the package contains many suggestions that may be counted on to lead to its indiscriminate and uncritical use.

Ergoapiol is an unscientific, shot-gun mixture of drugs having widely different therapeutic effects. Where the action of parsley is desired, the effects of ergot would ordinarily, be contra-indicated; furthermore, neither aloin or savin would be called for in conditions that demanded the effects of apiol. It would be impossible to predict the action of a mixture of this kind in the varying conditions for which its use is advised by the manufacturers. To combine four drugs of dissimilar action in fixed proportions for the routine treatment of conditions which have little in common except that they involve the female generative organs, is unscientific and absurd. The Council refused admission to Ergoapiol.--(_From The Journal A. M. A., Dec. 12, 1914._)

ERPIOL (DR. SCHRADER)

Report of the Council on Pharmacy and Chemistry

The original rules of the Council governing the acceptance of articles have recently been modified, particularly by adoption of Rule 10, which reads:

“Unscientific and Useless Articles.--No article will be admitted
which, because of its unscientific composition, is useless or
inimical to the best interests of the public or of the medical
profession.”

In view of these modifications, the Council is reconsidering the articles already accepted with the view of determining their compliance with the rules as amended. In line with this the Council reconsidered Erpiol (Dr. Schrader), manufactured by the William S. Merrell Chemical Company, and from the evidence given below concluded that one of the constituents, gossypin, is inert and its use unscientific. The Council therefore voted that Erpiol (Dr. Schrader) be omitted from New and Nonofficial Remedies and authorized publication of the following report.

W. A. Puckner, Secretary.

Erpiol

In consequence of the more thorough scrutiny now given by the Council to the therapeutic value of the remedies admitted to New and Nonofficial Remedies, the Council has reconsidered Erpiol (Dr. Schrader), previously accepted for New and Nonofficial Remedies. Erpiol (Dr. Schrader) is the name applied to capsules containing apiol, ergotin and gossypin, which are sold as an emmenagogue. The first two ingredients have a recognized value in the treatment of diseases of the female generative organs. The third, gossypin, is a preparation from cotton-root bark, belonging to the somewhat indefinite class of pharmaceutical preparations known as resinoids.

Cotton-root bark (_Gossypii radicis cortex_, U. S. P.) has been credited by some with pharmacologic and therapeutic properties, similar to ergot, especially in its action on the uterus; experiments on pregnant animals do not confirm this view. Most authorities on gynecology either make no reference whatever to the drug or ascribe little or no value to it. The preparations from the dried bark are inert.

From reports made to him, Professor J. U. Lloyd concluded (_Eclectic Med. Jour._, 1876, xxxvi, 545) that a prime fluidextract of fresh cotton-root bark is an active therapeutic agent and deserving the attention of the medical profession, while that of the dry bark is inert and worthless. The gossypin on the market is made from the dried bark.

Professor Lloyd, who is considered an authority on eclectic medicine, says: “Were it left to me to admit or exclude it, by reason of its therapeutical position, I should exclude it, because, in my opinion, it has never been demonstrated, in clinical practice, to be worthy of any therapeutic recognition whatever.”

As the available evidence indicates that gossypin is an inert preparation, Erpiol (Dr. Schrader) was considered in conflict with Rule 10 and the Council has therefore voted that it be deleted from New and Nonofficial Remedies.--(_From the Journal A. M. A., June 3, 1911._)

FALSE UNICORN (HELONIAS)

Report of the Council on Pharmacy and Chemistry

The Council voted to refuse to recognize false unicorn as a non-proprietary article and the following statements, submitted by a subcommittee, were ordered published.

W. A. Puckner, Secretary.

False Unicorn-Helonias

_Helonias dioica_, or more properly _Chamælirium luteum_, is a plant, preparations of which enter into various proprietary mixtures for diseases of the female pelvic organs. In the advertisements of these preparations it is usually credited with hemostatic powers and is asserted to be a uterine tonic.

There is practically no reference to this drug in reliable medical literature, and as there is no evidence worthy of credence to support the claims made for it, the drug was not considered deserving of a place in the Pharmacopeia. Hence, it may be regarded as a drug not worthy of attention of physicians.--(_From The Journal A. M. A., Nov. 27, 1909._)

FORMUROL

Report of the Council on Pharmacy and Chemistry

Formurol, Citrocoll and Aspirophen were submitted to the Council by the Cellarius Company of San Francisco. The manufacturers having failed to substantiate the claims they make for these products, the Council has voted that the preparations be refused recognition. The Council also authorized the publication of the following report, which deals particularly with one of the preparations--Formurol.

W. A. Puckner, Secretary.

Formurol is the product of the Chemische Fabrik Falkenberg, Falkenberg-Gruenau, near Berlin, Germany. The Cellarius Company, San Francisco, acting as selling agents for the United States, submitted Formurol (along with Aspirophen and Citrocoll, also made by the same firm) to the Council, with the statement that it is “hexamethylentetraminsodium-citrate,” and that it has the following composition: “C_{6}H_{7}O_{7}Na.C_{6}H_{12}N_{4}.”

Zernik,[46] who examined these products, reported that Aspirophen, Citrocoll and Formurol do not have the composition that is claimed for them by the Fabrik Falkenberg. Formurol, he states, is not a definite chemical compound, but a mixture of hexamethylenamin and sodium citrate. The agents were advised of this fact by the Council and were asked to submit evidence to substantiate their claims. No such evidence was submitted.

[46] Zernik: Arb. a. d. Pharmazeut. Inst. d. Univ. Berlin, 1907, iv, 46.

Since a compound having the composition that is claimed for Formurol is theoretically possible, the Council requested that the product be examined in the Association Laboratory to determine whether it still was the simple mixture reported by Zernik, or whether, perhaps, it now possessed the formula claimed for it. The following report was made by the Association chemists:

Formurol, as submitted to the Council, was in the form of tablets
weighing about 1 gm. each and appeared to be composed of a fine
white substance interspersed with some transparent particles.
The tablets were readily soluble in water, were odorless and
possessed a slightly acid taste. The aqueous solution responded
to tests for hexamethylenamin, citrate and sodium. To determine
whether hexamethylenamin was present in the free or the combined
state, the method of Zernik was employed. This consists in the
extraction of Formurol with chloroform, which dissolves out
hexamethylenamin, leaving insoluble sodium citrate. As the use of
the solvent, chloroform, would seem to preclude decomposition of
such a hypothetical compound as “hexamethylenamin-sodium-citrate,”
the extraction of hexamethylenamin from Formurol may be taken to
demonstrate its presence in the free state.

That Formurol is not a compound of hexamethylenamin, but a mixture
of hexamethylenamin and sodium citrate, was further indicated by
the appearance of the crushed tablets described above. Further,
on the low-power microscope the powder was found to be composed
of transparent crystals and white opaque particles which appeared
to be masses of minute crystals. When treated with chloroform the
transparent crystals dissolved, leaving the white masses intact,
demonstrating the presence of two distinct substances, one soluble
and the other insoluble in chloroform. It having been demonstrated
that the residue obtained by evaporation of chloroform could not be
weighed as hexamethylenamin, due to enclosed chloroform, the amount
of this substance in the residue was determined.

The method used has been described in the Report of the Chemical
Laboratory of the American Medical Association, Vol. I, p. 55,
and depends on the decomposition of hexamethylenamin by means of
sulphuric acid to form ammonium sulphate and formaldehyd. From this
solution the ammonia is liberated, distilled and determined by
titration and from the ammonia found the amount of hexamethylenamin
is calculated. By this method Formurol was found to contain (_a_)
35.42 per cent. and (_b_) 35.32 per cent., or an average of 35.37 per
cent. hexamethylenamin. The residue insoluble in chloroform was shown
to consist essentially of disodium hydrogen citrate by determining
the amount of sodium (Na) contained in Formurol. The percentage of
sodium calculated from the amount of sodium sulphate found was (_a_)
11.38 per cent. and (_b_) 11.20 per cent., or an average of 11.29 per
cent., equivalent to 62.50 per cent. disodium hydrogen citrate.

As a check on this determination, the amount of material contained
in Formurol which is insoluble in chloroform was determined. It was
found to be (_a_) 63.23 per cent. and (_b_) 63.49 per cent., making
an average of 63.36 per cent., and thus agreeing fairly well with the
results obtained when the sodium content was assumed to be disodium
hydrogen citrate. From this analysis it appears that Formurol is
not a definite compound of hexamethylenamin and sodium citrate, but
instead is a mixture of these substances consisting approximately of
hexamethylenamin 35.37 per cent. and sodium acid citrate (disodium
hydrogen citrate) 63.36 per cent., practically a mixture of 1 part
hexamethylenamin and 2 parts sodium acid citrate. These results agree
with those reported by Zernik[47] and show that the product now, as
then, is not true to claims.

[47] Therap. d. Gegenw., February, 1909.

In view of the findings of the laboratory, it is recommended that Formurol be refused recognition. As the exploitation of well-known remedies under false and misleading names is detrimental to the progress of medicine, it is recommended that publication of this report be authorized.

[Editorial Note: This report illustrates once more the value of
the Council on Pharmacy and Chemistry and the Chemical Laboratory
to the medical profession. Before the Council was organized there
was no agency to protect the physician’s interests in the matter
of pharmaceuticals. Under the old régime Formurol would have been
heralded as a new “synthetic” of the most approved made-in-Germany
type--and the claims would have gone unchallenged. To-day its status
is made clear and the profession is informed. Only those who have
closely studied the question can realize what a wonderful power for
commercial probity the Council has proved. Under the _laissez faire_
system of the past, many large pharmaceutical firms gave little
attention to the accuracy of the claims made for their products. If
the advertising gave good “pulling” results, that was all that was
asked or expected. Within the past five years a wonderful change has
taken place in this regard, and firms of the better class have so
modified their advertising as to make it not only conservative in
tone, but to approximate scientific accuracy.]--(_From The Journal
A. M. A., Jan. 21, 1911._)

GASTROGEN TABLETS

Report of the Council on Pharmacy and Chemistry

The Bristol-Myers Co., Brooklyn, N. Y., sells Gastrogen Tablets which
are described as “A Neutralizing Digestive” to be “used in connection
with Sal Hepatica.” Sal Hepatica, it will be remembered, is another
product of the Bristol-Myers Company and has been the subject of
previous unfavorable comment. The label on a recently purchased
package of Gastrogen Tablets contains the following:

“For gastric distress, weak stomach and dyspepsia, one to two
tablets after eating; repeat in half an hour if needed.

“Also indicated in nausea, flatulence, sour stomach and heartburn.”

While these recommendations sound as if they were addressed to the
public, Gastrogen Tablets are advertised in medical publications and
hence come within the scope of the Council. Gastrogen Tablets are said
to be composed of pepsin, calcium carbonate, calcium phosphate and
“aromatics.” As each tablet, according to the label, contains 7 grains
of calcium carbonate (chalk), the recommended dosage would in most
cases be sufficient to neutralize the gastric fluids in the stomach
and would thus tend to prevent the pepsin from exerting its digestive
effects. The means adopted to relieve one symptom of dyspepsia,
in other words, defeats the action of the means for relieving the
indigestion. The fact is that patients who need an antacid do not
need pepsin, while those who need pepsin will be harmed by the
administration of an antacid. Gastrologists hold that, except in rare
cases, the evidence tends to show that wherever there is a sufficiency
of hydrochloric acid there is a sufficiency of pepsin. When pepsin
is lacking it should be administered along with hydrochloric acid to
make it effective. The Council voted that Gastrogen Tablets be refused
recognition.--(_From The Journal A. M. A., Dec. 12, 1914._)

GLYCO-HEROIN, SMITH

Report of the Council on Pharmacy and Chemistry

The following report was submitted to the Council by a referee and publication authorized.

W. A. Puckner, Secretary.

Glyco-Heroin, Smith (Martin H. Smith Co., New York) is marketed in a showy “patent-medicine” type of package, the label on which announces the presence of 1/2 grain of heroin to the fluidounce and admits the presence of 3.5 per cent. alcohol, an active ingredient that is not discussed in any way in the literature sent out by the manufacturer.

The composition of Glyco-Heroin, Smith, is given as follows: “Each teaspoonful represents: Heroin 1/16 grain, White Pine Bark 3-1/2 grains, Ammonium Hypophosphite 3 grains, Balsam Tolu 1/4 grain, Hyoscyamus 1 grain, Glycerin Q. S.” The alcohol is not mentioned in the formula.

The advertising matter says of the merits of the formula:

“Despite the fact that heroin, which is universally recognized
as an invaluable respiratory sedative, is a conspicuous element
of Glyco-Heroin, Smith, the other constituents, henbane, ammonia
hypophosphite, balsam tolu and white pine bark are factors of no
less importance; indeed, it is through the concerted action of
its several ingredients that the preparation proves so notably
beneficial in the class of affections in which it is indicated.
The constantly increasing popularity of the preparation in the
treatment of respiratory affections is the best adducible evidence
of its value in such disorders.”

The absurdity of this assertion will be appreciated on comparing the nature, quantities and activities of the several ingredients. Thus, while heroin, a potent habit-forming drug, is present in unusually large proportions, tolu, an innocuous or comparatively harmless product, is said to be represented by 1/4 grain, a relatively small quantity, hardly sufficient to impart even a distinctive taste or flavor. Ammonium hypophosphite, in the amount said to be present, may be considered to be practically useless, while the dose of hyoscyamus, an additional narcotic, is fairly large. The white pine bark present is probably as active as would be a corresponding amount of white pine shavings or of turpentine sufficient to give the preparation a slight odor. The vehicle, glycerin, is claimed to be “notably advantageous,” but not a word occurs in the discussion by the manufacturer in regard to the presence of alcohol, which is certainly quite as active medicinally as the balsam of tolu and contributes fully as much to the flavor or taste of the preparation as does the white pine bark.

In prominent type on the outer label of the trade package we are told that the preparation is intended for the treatment of “COUGH, ASTHMA, PHTHISIS, PNEUMONIA, BRONCHITIS, LARYNGITIS, WHOOPING-COUGH AND KINDRED INFECTIONS.” In much smaller type: “Glyco-Heroin (Smith) is distinctly a product designed expressly for the use of physicians.” The circular included with the trade package, however, bears statements which would tend to encourage self-drugging by the layman, and in view of the manner in which the preparation is exploited are undoubtedly intended to do so. For instance:

“_Bronchitis._--In the acute form of bronchitis, Glyco-Heroin
(Smith) acts most happily. It tends to diminish the congestion and
inflammation of the lining of the air passages, relieves the pain
and institutes repair....

“_Phthisis._--In the treatment of the cough of phthisis,
Glyco-Heroin (Smith) is used with the most gratifying results.
It checks the night sweats, acts favorably upon the reflexes,
increases expectoration and induces refreshing sleep.

“_Asthma._--The preparation diminishes the intensity of the
paroxysms and lengthens the intervals between their recurrence.
By the administration of the preparation, asthmatic attacks can
frequently be aborted.

“_Pneumonia._--In the initial stage of pneumonia, the preparation
exercises a calming, antipyretic and sedative effect. In the latter
stages of the disease, the analgesic and expectorant properties of
the product are well displayed.

“_Whooping-Cough._--Administered in doses of from five to ten drops
this preparation affords surprisingly satisfactory results. The
cough rapidly loses its spasmodic character and the frequency of
the paroxysms is considerably diminished.”

How cruelly misleading the literature put out by the manufacturer of this nostrum is, will be apparent from a comparison of the rather large dose of heroin in a teaspoonful of the nostrum and the directions on the package that:

“The adult dose of Glyco-Heroin (Smith) is one teaspoonful repeated
every two hours or at longer intervals, as the case may require.

“Children of 10 or more years, from a quarter to a half-teaspoonful.

“Children of 3 years or more, 5 to 10 drops.”

A WICKED FALSEHOOD

Included in much of the advertising matter that has been put out is the bare-faced untruth that the preparation does not produce narcotism or habituation. Here is a quotation from an undated circular:

“Glyco-Heroin (Smith) is decidedly preferable to preparations
containing codeine or morphine, by reason of the fact that it
does not produce narcotism, constipation, gastric disturbance nor
habituation, even though its administration be protracted.”

That this assertion is not in keeping with facts is evidenced by the recent report of a study on the sale and use of heroin made by the U. S. Department of Agriculture. From the information gathered it appears that the sales of heroin and heroin-containing preparations have increased greatly, particularly in those states which have rigid laws preventing the indiscriminate sale of morphin and cocain. Investigation of the subject establishes the fact that many drug victims who formerly used morphin and cocain, and who under the new laws find it difficult to obtain these substances, have begun using heroin, the sale of which is not as yet carefully restricted under state laws. The drug is said to be fully as dangerous as morphin, and by many is held to be much worse, for the reason that it occasionally kills the victim outright, and its habitual use is far harder to overcome than that of other drugs.

Phillips,[48] in discussing the prevalence of the heroin habit, reports, among others, the case of a physician aged 60 who began to take heroin because he suffered from a chronic cough and thought there was no danger of habit from the use of this drug because he believed the statements of various manufacturing firms who claimed that there was no danger of habit.

[48] Phillips, John: Prevalence of the Heroin Habit, The Journal A. M. A., Dec. 14. 1912, p. 2146.

In a pamphlet now being distributed to the medical profession, entitled, “Glyco-Heroin (Smith), an exposition of its components together with references to its value in the treatment of Bronchitis, Cough, Cough of Phthisis, Laryngitis, Pneumonia and allied disorders of the Respiratory Tract,” the several alleged uses of the nostrum in the treatment of cough, “Regardless of the nature of its underlying cause, ... whether of recent origin or of long duration,” are discussed at length, and eminent practitioners with degrees extending the width of the printed page are quoted in support of the statements made. While it may be permissible for a theoretically trained medical tyro who lays claim to the right of appending the abbreviations M.A., M.D., D.C.L., L.R.C.P. to his name to laud a heterogeneous habit-forming cough-syrup like Glyco-Heroin, Smith, similar testimonials from a man entitled to append Ph.G., M.S., M.D. to his name makes one doubt the value of the training, either scientific, pharmaceutical or medical, that has been given the poor unfortunate who, according to his own statements, indiscriminately doses a female patient of 7 and a male patient of 40 with huge doses of heroin every two, four or six hours.

The danger of contributing to the spread of the heroin habit by the use of preparations of this type is indicated by an editorial in The Journal of the American Medical Association,[49] which points out that although heroin and its hydrochlorid have been in use but a few years they have already established themselves among the habit-forming drugs and have become sufficiently conspicuous in this respect to awaken the thinking public to the deplorable results for which they may become responsible. Phillips,[1] in the article mentioned above, quotes Petty, who reports that in the last 150 cases of drug habit coming under his care he saw eight cases of heroin addiction. Three of these were initial cases; in one the patient had been cured of the opium habit, but following an operation heroin was prescribed, and the habit followed. The remaining four patients purposely substituted heroin for morphin, to which they had been addicted.

[49] Facts about Heroin, Current Comment, The Journal A. M. A., Dec. 21, 1912, p. 2262.

THE GROWTH OF HEROIN ADDICTION

The imminent danger of substituting heroin for either morphin or cocain is shown by the fact, reported by the U. S. Department of Agriculture, that during the early months of 1913 the coroner’s office in Philadelphia County, Pa., held inquests on five sudden deaths from heroin poisoning. In each case the victim was a heroin fiend and took an overdose. Drug fiends are apparently able to consume relatively large quantities of morphin or cocain, but any sudden and material increase in the amount of heroin taken is liable to prove fatal. As indicating the wide sale of this substance, it is known that one druggist in Pennsylvania whose store is located in an undesirable section of his city has been buying heroin tablets in 25,000 lots.

GLYCO-HEROIN, SMITH, A “PATENT MEDICINE”

The popularity of Glyco-Heroin, Smith, as a household nostrum is suggested by the fact that one of the larger department-store type of drug-stores in the city of Philadelphia lists this preparation in its “patent-medicine” catalogue at $1.75 per bottle and sells it freely to all who care to buy. This is due to the fact that Pennsylvania, like many other states, does not include heroin in the prohibited list of habit-forming drugs that can be supplied only on physicians’ prescriptions.

To what extent Glyco-Heroin, Smith, is responsible for developing the rapidly growing heroin habit is of course problematic. It is reasonable, however, to suppose that a preparation, each teaspoonful of which contains so large a dose of heroin as does this nostrum, when taken as repeatedly and as indiscriminately as is directed by the manufacturer, would offer possibilities for harm sufficient in number to induce the thinking medical practitioner to avoid its use altogether and at least to suggest to even the most commercial dabbler in the healing art the desirability of carefully considering its potency for harm before endorsing its use in the treatment of “cough and kindred affections.”--(_From the Journal A. M. A., June 6, 1914._)

GLYCO-THYMOLINE

Report of the Council on Pharmacy and Chemistry

The Council, having voted that Glyco-Thymoline be refused recognition, authorized publication of the following report.

W. A. Puckner, Secretary

Glyco-Thymoline (Kress and Owen Company, New York) is a typical example of a “patent medicine” advertised to the public through the doctors. Bottles of the mixture with the name blown in the glass are issued to physicians for distribution to patients, and the circular which comes around the bottle more or less directly recommends it for use in almost every form of infectious disease.

COMPOSITION AND VARYING FORMULAS

Different formulas for Glyco-Thymoline have appeared. At one time it was said to contain:

“Sodium 24, Boric Acid 4, Benzoin 4, Acid Salicylic 0.33,
Eucalyptol 0.33, Thymoline 0.17, Betula Lenta 0.08, Menthol 0.08,
Pini Pumilionis 0.17, Glycerin and solvents, q.s.”

Another formula, which appeared about the same time, was:

“Benzo-Salicyl. Sod. 33.33, Eucalyptol 0.33, Thymol 0.17,
Salicylate of Methyl from Betula Lenta 0.16, Pini Pumilionis 0.17,
Glycerin and solvents q.s.”

A later formula was like the second except that it included “Menthol, 0.08.”

Analysis in the chemical laboratory of the American Medical Association showed that Glyco-Thymoline contained borax, but no boric acid; sodium salicylate, but no salicylic acid; sodium benzoate, but no benzoin; the compound benzo-salicyl. sod. could not be determined, but a mixture of sodium benzoate and sodium salicylate was demonstrable.[50] Later Puckner pointed out[51] that while such a combination as benzo-salicylate of sodium is known, it could not possibly be present in Glyco-Thymoline because the alkalinity of this mixture would decompose the compound. As the manufacturers evidently recognize that false formulas can no longer be made plausible, only vague statements as to the composition are now offered.

[50] The Formula for Glyco-Thymoline, Pharmacology Department, The Journal A. M. A., Jan. 9, 1909, p. 147.

[51] Puckner, W. A.: Rep. Chem. Lab., A. M. A., 1910, iii, 7.

Two points should be noted in this connection:

1. Glyco-Thymoline conflicts with Rule 1 of the Council on Pharmacy and Chemistry, which declares that no article shall be accepted for inclusion with New and Nonofficial Remedies unless its composition be furnished.