Chapter XXIV: Appendix (5)

“That the economy will tolerate to a surprising degree substances
directly introduced through the blood stream is now well known.
By the intravenous injection of 10 c.c. of methyl-phenol serum we
throw into the human body a massive dose of an alien substance.
The immediate effect of this injection is upon the central nervous
system. The recipient usually becomes either pale or suffused, he
has a ringing in his ears, has a sensation of great altitude, and
occasionally has a dryness of the fauces and a metallic or a garlic
taste.”

“In some patients secondary reactions occur in from one to four
hours after injection. The phenomena we have observed in these
secondary reactions are pronounced chill and rigor ...”

There is no doubt that considerable harm may be done by the intravenous and by the intraprostatic administration of these preparations and until there is good evidence showing the therapeutic value of the treatment, the routine use of these preparations, except perhaps at hospitals in selected and well controlled and carefully guarded cases, is to be strongly discouraged.

When the foregoing statement was sent to the Mulford Company for comment, the firm submitted a letter from Dr. Perry Townsend to the Mulford Company in which he declared that the results obtained with the Cano preparations had been satisfactory and without untoward results. In this letter, Dr. Townsend proposed that a series of injections with these preparations be carried out under the observation of members of the Council and the supervision of Dr. Cano or himself.

The report of the Council, the letter from the Mulford Company and that of Dr. Townsend were sent to a number of urologists for their opinion concerning this whole matter. It was explained that the referee held that no reason had been presented which would warrant the Council to depart from its customary procedure, namely, to require that clinical evidence be submitted in the form of published reports which permit investigation and verification by independent observers but that, before making further recommendation to the Council, he desired the opinion of urologists of recognized standing concerning the report submitted to the Mulford Company. All replies received approved the Council’s position.

The following is one of the replies received:

Your letter in regard to Normal Phenol Serum (Cano) and
Methyl-Phenol Serum (Cano) received. I wish to state that I have
read the correspondence between the Council and H. K. Mulford Co.
and in my opinion the referee and the Council are quite correct in
their attitude in the matter. In my opinion I would emphasize the
following:

(1) There is absolutely nothing about the remedies directed
_specifically_ against the gonococcus and no evidence to show that
any action against them is obtained. As we know there are certain
states of normal serum which are highly toxic and any normal
serum from another animal will produce disturbances in man when
injected intravenously--particularly if repeated. The addition of
substances to serum normal or otherwise is apt to and frequently
does render that serum highly toxic! The substances added in the
instances referred to--phenol and methylene blue are not in any
way calculated to lessen the toxicity of serum. The element of
danger existing in the indiscriminate use of serums intravenously
is, in my opinion, increased by the addition of the substances
mentioned, and it would be unwise to encourage the general use of
any such remedies. Furthermore the products are condemned by the
very evidence of the originators and their admissions are quite
sufficient to deter anyone from using the products as they suggest.

As to the intraprostatic injections with the serums it does not
at all meet my views; although the introduction of serums by this
route have been frequently advocated and I have personally carried
this mode out I cannot allow the impression to go out that it
could be done in a routine manner--nor that no ill results could
follow--for I have seen otherwise. Furthermore from theoretical
standpoint serums need not be given in this way.

In consideration of the opinion expressed by the Council’s consultants the referee recommended that Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) be declared ineligible for New and Nonofficial Remedies because of conflict with Rule 6 (unwarranted therapeutic claims) without considering possible conflicts with other rules, and that publication of the report be authorized.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 85._)

SOAMIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Soamin is the name under which the firm of Burroughs Wellcome and Company sells its brand of sodium arsanilate. The Council directed the omission of Soamin from New and Nonofficial Remedies and authorized publication of the report which appears below after the proprietors of the product had declined to withdraw or suitably revise the unwarranted therapeutic claims which it made.

W. A. Puckner, Secretary.

The proprietary brand “Soamin” of sodium arsanilate was admitted to New and Nonofficial Remedies several years ago at a time when the therapeutic value of arsanilic acid had not been definitely determined. Experience with this drug has shown that it is far more dangerous and also has a more limited field of usefulness than was at first recognized. The proprietors of the Soamin brand have continued to include in the list of conditions in which it “would seem” to be a “very effective agent” cerebrospinal meningitis and pellagra; in fact, meningitis is the first in the list of conditions mentioned, syphilis the second and pellagra third. In support of their belief in the efficacy of the remedy in meningitis, three reports, published from six to nine years ago, are quoted. In one of these it is stated that two patients “were cured”; in another report, seven of eight patients in whom the clinical, but not the microscopic, diagnosis of meningitis had been made were reported as having recovered; in the third report, fifty-six of ninety cases were reported cured; in this larger series of cases the author neglects to state the method of administration. The firm quotes but one paper (which is a very uncritical report) in regard to pellagra.

It seems to the Council that the evidence of value of sodium arsanilate in these conditions (which are now treated by more rational methods) is too slight to justify the emphasis laid on it by the firm, especially as sodium arsanilate is admittedly a dangerous agent, several cases of blindness having been reported from its use.

For these reasons it was voted to omit Soamin from New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 89._)

SOME MIXED VACCINES NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

The consideration of the following “mixed” vaccines was requested by F. I. Lackenbach, San Francisco:

Special Bacterial Vaccine No. 2 (Staph-Strep. Bacterin) containing
killed _Staphylococcus albus_, _Staphylococcus aureus_ and
streptococcus.

Special Bacterial Vaccine No. 3 (Pneumo-Staph-Strep. Bacterin)
containing killed _Staphylococcus albus_, _Staphylococcus aureus_,
streptococcus and pneumococcus.

Special Bacterial Vaccine No. 4 (Pneumo-Staph-Strep-Coli Bacterin)
containing killed _Staphylococcus albus_, _Staphylococcus aureus_,
_Staphylococcus citreus_, _Bacillus coli_, streptococcus and
pneumococcus.

Special Bacterial Vaccine No. 5 (Influenza Combined Bacterin)
containing killed _Staphylococcus albus_, _Staphylococcus aureus_,
_Bacillus Friedländer_, _Bacillus influenzae_, _Micrococcus
catarrhalis_, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 11 (Pneumo-Strep. Bacterin)
containing killed streptococcus and pneumococcus.

Special Bacterial Vaccine No. 15 (Combined Whooping Cough Bacterin)
containing killed _Bacillus pertussis_, _Staphylococcus albus_,
_Staphylococcus aureus_, _Micrococcus catarrhalis_, _Bacillus
influenzae_, streptococcus and pneumococcus.

Special Bacterial Vaccine No. 16 (Mixed Gonococcus Bacterin)
containing killed gonococcus, _Staphylococcus albus_,
_Staphylococcus aureus_, _Bacillus coli_, _diphtheroid bacillus_,
streptococcus and pneumococcus.

Mr. Lackenbach states that these bacterial mixtures were prepared for him by E. R. Squibb & Sons. Their sale in interstate commerce is permitted under the license granted to the latter firm by the U. S. Treasury Department. However, no evidence of any kind was presented to the Council proving the therapeutic efficacy of the several mixed vaccines. As a mixture of two or more kinds of organisms is accepted for New and Nonofficial Remedies only if there is satisfactory evidence that its therapeutic use is rational, the Council declared the several vaccine mixtures ineligible for New and Nonofficial Remedies (Rule 10).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 90._)

SOMNOFORM

Report of the Council on Pharmacy and Chemistry

The Council examined the available evidence for Somnoform, sold by Stratford-Cookson Company, successors to E. de Trey and Sons, and found the preparation inadmissible to New and Nonofficial Remedies. The Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Somnoform is sold in the United States by Stratford-Cookson Company, successors to E. de Trey and Sons. According to the label on a package of Somnoform sent the Council.

“This mixture contains Chloride of Ethyl, 83 per cent.; Chloride of
Methyl, 16 per cent.; Bromide of Ethyl, 1 per cent.”

Although Somnoform has been on the market for a long time, the published reports present no proof that it is superior to ethyl chlorid used alone. Moreover, the published reports and statistics do not necessarily apply to the Somnoform now sold for the reason that mixtures of varying composition have been sold as Somnoform in the past. Thus, when Somnoform was considered by the Council in 1909, it was claimed to be composed of chloride of ethyl, 60 per cent.; chloride of methyl, 35 per cent., and bromide of ethyl, 5 per cent. Federal chemists found, however, that it contained no bromide of ethyl (Notice of Judgment No. 571). It is a question, therefore, whether a given report applies to a mixture containing 5 per cent. bromide of ethyl, 1 per cent. of this substance, or none at all.

The present advertising booklet for Somnoform does not present acceptable evidence of the therapeutic value of the preparation. An ignorance concerning the elementary facts of physiology and pharmacology is evident in the second sentence: when having stated that “Somnoform is the result of several years of study and investigation by Dr. George Rolland, Dean of the Bordeau Dental School,” the pamphlet continues: “He sought an anesthetic which would enter, dwell in, and leave the body in the same manner that oxygen does....”

The claim as to the value of the 1 per cent. of ethyl bromide in the mixture is highly improbable; certainly no evidence in support of the claimed value of this constituent is available to the referee.

No evidence is submitted which proves the claim of superiority of Somnoform over similar preparations, asserted in the following:

“The peculiar manner in which the elements are combined is what
makes Somnoform at once so efficient and so safe.”

The Council declared Somnoform inadmissible to New and Nonofficial Remedies because, in the absence of acceptable evidence showing its exceptional safety and value, the claims are unwarranted (Rule 6), and because the name of the mixture is not descriptive of its composition (Rule 8).--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 90._)

TABLETS FORMOTHALATES

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report which declares Tablets Formothalates (Tailby-Nason Company, Boston, Mass.) ineligible for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Tablets Formothalates are sold by Tailby-Nason Company, Boston, Mass. On the label a formula is given: “Constituents: Acetanilid 2 gr.; phenolphthalein 1/2 gr. In a balanced combination with Hexamene [a name sometimes applied to hexamethylenamin] and Oil of Cinnamon. Indications: Influenza, Colds, Grippe, Headache, Neuralgia, Rheumatism.” The same formula is given in advertisements and in this advertisement it is claimed that they are “For Influenza and Grip” and if “given in the acute stage may avert a serious attack” (_Boston M. & S. J._, Oct. 3, 1918). The dose is given as one to two tablets at 6 p. m. and repeat at bedtimes.

The A. M. A. Chemical Laboratory reported that the tablets weigh an average of 0.4882 Gm., or 7-1/2 grains; that they _have_ the odor and taste of cinnamon; and that they contain hexamethylenamin, are neutral and therefore give up no formaldehyde in the presence of water alone. The Laboratory further reported that they contain phenolphthalein and acetanilid. These tablets were directed to be taken internally and therefore their effect was not intended to be local.

The amount of hexamethylenamin was not determined, but in any case could not exceed 5 grains per tablet. It is evident that 4 grains of acetanilid and 10 grains of hexamethylenamin and 1 grain of phenolphthalein (in two tablets) “if given in the acute stage” of influenza would not “avert a serious attack,” as claimed in the advertisements.

The Council declared Tablets Formothalates inadmissible to New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 92._)

TRIPLE ARSENATES WITH NUCLEIN

Report of the Council on Pharmacy and Chemistry

The Council has declared Triple Arsenates with Nuclein No. 1 and Triple Arsenates with Nuclein No. 2, tablets marketed by the Abbott Laboratories, inadmissible to New and Nonofficial Remedies because unwarranted therapeutic claims (Rule 6) are made for them and because they present an illogical combination of drugs (Rule 10). The publication of the following report has been authorized by the Council.

W. A. Puckner, Secretary.

The following claims are made for Triple Arsenates with Nuclein:

“Puts ‘pep’ and strength back into that patient recovering from
Spanish Influenza, pneumonia, typhoid, or surgical operation. An
extremely powerful reconstructive tonic. Try it for that ‘run down’
feeling.”

Triple Arsenates with Nuclein is said to contain “Strychnin Arsenate gr. 1/128, Quinin Arsenate gr. 1/64, Iron Arsenate gr. 1/64, Nuclein Solution mins. 4.” A second preparation, of double strength--Triple Arsenates with Nuclein No. 2--is also advertised. The Council voted not to accept these preparations for New and Nonofficial Remedies on the following grounds:

The quantities of quinin, iron and nuclein in the doses represented in these mixtures are negligible; thus, one tablet of Triple Arsenates with Nuclein containing 1/64 grain of quinin arsenate contains only about 1/90 grain of anhydrous quinin; the tablet containing 1/64 grain of iron arsenate contains 1/210 grain of iron; 4 minims of the nuclein solution (assuming it to be the “Nuclein Solution-Abbott”) would contain but 2/5 of a grain of nuclein--a substance which even in large doses is of questionable therapeutic value. The amounts of iron and nuclein contained in doses of this preparation are insignificant in comparison with the amounts present in ordinary foods. The only substances present in even small therapeutic doses are strychnin and arsenic. The effects of arsenic and strychnin are very different and there are comparatively few conditions in which they should be prescribed at the same time. Hence a preparation containing these two in fixed proportions is illogical.--(_From Reports of Council on Pharmacy and Chemistry, 1919, p. 92._)

“ANTI-PNEUMOCOCCIC OIL” AND THE USE OF CAMPHOR IN PNEUMONIA

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below. This report declares “Anti-Pneumococcic Oil” (a solution of camphor in oil sold by Eimer and Amend, New York) ineligible for New and Nonofficial Remedies because (1) the recommendations for its use in pneumonia are not warranted by the evidence, (2) the name is not descriptive of its composition but is therapeutically suggestive, and (3) the sale of a solution of camphor in oil under a name nondescriptive of its composition is unscientific and a hindrance to therapeutic progress.

W. A. Puckner, Secretary.

The Council having decided to consider Anti-Pneumococcic Oil (Eimer and Amend, New York), the preparation was assigned to the Committee on Therapeutics for report. The report that follows was made by a member of this committee:

According to the advertising, Anti-Pneumococcic Oil is a “twenty-five per cent. solution of camphor in a thin oil” which was “originated” by August Seibert, M.D. The following directions are given for its use:

“10 c.c. (150 minims) to every 100 pounds of body weight, to be
injected hypodermically every eight to twelve hours in pneumococcic
pneumonia, as soon after the initial chill as possible.”

It is claimed that the prescribed dose one hour before general anesthesia begins, “safeguards against postoperative pneumonia,” and, that “animals can so be immunized against later and otherwise fatal intravenous pneumococcic infection (Boehnke, Institute for Experimental Therapy, Frankfort).” The advice is given:

“In pneumococcic meningitis, endocarditis and pleuritis, 3% of
salicylic acid should be added to this oil.”

In an article by Seibert, “Camphor and Pneumococci” (_Medical Record_, April 20, 1912), a reprint of which is used to advertise Anti-Pneumococcic Oil, previous work (_München, med. Wchnschr._, No. 36, 1909) is mentioned as the starting point for the use of camphor in pneumonia. In this article, the author reports his first case, that of a young woman who entered St. Francis’ Hospital on the third day after the initial chill “with the symptoms of severe toxemia (unconscious, temperature 105.5 F., pulse 130, and respiration 40) and involvement of both lower lobes.” “Large doses of camphor,” 12 c.c. of a 20 per cent. solution, were injected hypodermically “every twelve hours, resulting in _gradual_ improvement and recovery by the fourth day, without a crisis.” Seibert reports success in its use in twenty-one cases, but gives no case histories or protocols. He admits, however, that in four out of sixteen cases, following the first twenty-one so reported certain “limitations of this treatment were observed,” and a “sudden rise of temperature in two patients on the second and third days of treatment, respectively, proved to be due to pneumococcic nephritis, promptly subdued by appropriate doses of urotropin, while the camphor injections were continued and resulting in speedy recovery.” He further admits that empyema occurs, and states: “This proves that the camphor brought into the blood cannot prevent the as yet living organisms, constantly entering the blood current from the affected alveoli, from colonizing in the renal and pleural tissue.”

He reports, among thirty-seven patients treated in this manner, one death, that of a man 68 years old, weighing 200 pounds, with a fatty heart. Heart failure was the real cause of death. Seibert also reports some very incomplete experimental work; Dr. Hensel, assistant and pathologist of the German Hospital, found that “1/10,000 part of camphor added to the usual culture media inhibited the growth of pneumococci, while the controls all thrived”; Dr. J. C. Welch, pathologist of the Lying-in Hospital, found that rabbits infected with lethal doses of pneumococcus cultures intravenously were saved by large doses of camphorated oil; fragmentary protocols are given. The assistant pathologist of St. Francis’ Hospital carried on the experimental work, adding salicylic acid to the camphor. No blood cultures are reported. The conclusion reached by Dr. Seibert is that salicylic acid up to 3 per cent., added to the camphorated oil, is effective in preventing pleural infection. In the article by Dr. Seibert, there appear most sketchy reports of cases, recovery being reported without crisis in from three to nine days.

The referee has made a careful search of the literature, with the following results: Boehnke (_Berl. klin. Wchnschr._ 50:818, 1913), using white mice, failed to confirm the experiments reported in Seibert’s paper, unless camphorated oil were given before the pneumococci, and even then, he felt that the results were too irregular to be of great significance. When given with anti-pneumococcic serum, however, he felt that there was some benefit to be seen by the administration of camphor; his protocols, however, are not detailed. There is no report of blood cultures, etc.

Another worker, H. Leo (_Deutsch. med. Wchnschr._ 39:690, 1913), reported that camphor water given intravenously prolonged the lives of thirty-eight rabbits inoculated with pneumococci. Here again there were no adequate protocols and very little evidence of careful experimental work appears.

In the literature of the past ten years, there appear sketchy clinical articles on the value of huge doses of camphor in pneumonia. Markevitch (_Russk. Vrach_, June 27, 1914; abstr., The Journal, Dec. 5, 1914, p. 2081) treated 226 cases of pneumonia with 5 c.c. of camphorated oil hypodermically four times daily, at the same time giving digitalis (amount not stated), with a mortality of 6.6 per cent., whereas, in 322 cases untreated, there was a mortality of 13.3 per cent. He reports 133 grave cases; sixty-six received no camphor; 48 per cent. died. Of sixty-seven treated with camphor, only 22 per cent. died. He reports temperature falling by lysis when camphor is used, and comments on the symptomatic improvement following its use. With the great variation in the clinical course of pneumonia, the above figures, though suggestive, certainly need further support before the routine use of camphor as recommended by Seibert can be sanctioned.

Later articles found on the subject refer to it in a very cursory way, giving no protocols and no cases, and giving the referee the feeling that the conclusions were very impressionistic.

RÉSUMÉ

After a careful search of the literature, the referee concludes that: Huge doses of camphor, to 250 grains in twenty-four hours, may be given to man without serious results. No satisfactory evidence, however, appears that camphor has a specific germicidal action on pneumococci (similar to that of ethylhydrocuprein). The clinical evidence, as found in the literature, is certainly of very little value. It appears that the sale of a simple solution of camphor in oil under the guise of “Anti-Pneumococcic Oil” is to be deplored (a 20 per cent. solution of camphor in cottonseed oil is official in the U. S. Pharmacopeia as camphor liniment). It is recommended that the preparation be held inadmissible to New and Nonofficial Remedies because exaggerated therapeutic claims are advanced for it, and because the name is not descriptive of the composition, but is, instead, therapeutically suggestive.--(_From The Journal A. M. A., Jan. 3, 1920._)

DIAL “CIBA”

Report of the Council on Pharmacy and Chemistry

Dial “Ciba” has not been accepted for “New and Nonofficial Remedies” because, as the report which follows shows, unwarranted claims are made for the product. It is a definite new chemical compound which might be made eligible for N. N. R. if misleading therapeutic claims were eliminated. The Council directed that Dial “Ciba” be included with Articles Described but Not Accepted, so that physicians might be informed with regard to its character and properties.

W. A. Puckner, Secretary.

Dial “Ciba” is a hypnotic manufactured by the Society of Chemical Industry of Basle, Switzerland, and is sold in the United States by A. Klipstein and Company, Inc., New York. Chemically, Dial “Ciba” is diallylbarbituric acid and is, therefore, closely related to diethylbarbituric acid or barbital (“veronal”).

The claims made for Dial “Ciba” are (1), that the “allyl” group in its molecule makes it more readily decomposed by oxidizing agents than barbital, which contains the “ethyl” group; (2) that because of this ease of oxidation, it is more readily decomposed in the body and more rapidly and completely eliminated, and (3) that because of its alleged rapid elimination, it is devoid of the after effects of barbital and other hypnotics.

The Council took up the substance in February, 1918, and referred the matter to the referee in charge of barbital preparations. The referee considered unwarranted the claim that Dial “Ciba” did not have the after-effects of other hypnotics due to its alleged total decomposition in the body. The American agents, A. Klipstein and Company, were informed of the referee’s objections. Their attention was also called to the fact that, notwithstanding the claimed absence of after-effects in one part of the advertising, other parts of the same advertising admitted certain post-hypnotic effects of the product. It was pointed out also that while it was claimed in one of the advertising circulars that lowering of the blood pressure is never observed after administration of Dial “Ciba,” yet two of the authors quoted in the same circular definitely stated that a lowering of the blood pressure followed even small doses of the drug and these authors warn against this very danger in certain conditions.

A year later, a circular letter sent out by A. Klipstein and Company reiterated the claim that the asserted decomposition of Dial “Ciba” in the body prevents after-effects, the drug being still contrasted with barbital (“veronal”). In view of the reiteration of this highly improbable claim, the referee undertook to study the comparative action of Dial “Ciba” as compared with other hypnotics. It was found that the actions of Dial “Ciba” are not distinguishable, qualitatively, from those of barbital, there being no perceptible difference in the after-effects or in the nature of the side actions. In toxic doses, both caused profound depression with the temperature falling to that of the room (or about one degree above), the respiration being extraordinarily slow and shallow as one would expect with lowering of the temperature. There were also the same evidences of nausea that are so frequently seen after toxic doses of the various hypnotics of this group. In view of these results, the Council declared that it is unwarranted to claim freedom from after-effects for Dial “Ciba.”

The Council held that the following statement is unwarranted:

“The therapeutic field for Dial ‘Ciba,’ as shown by tests on
rabbits, is just as broad as the field for Diethylbarbituric Acid.”

Tests on rabbits do not and cannot show the breadth of the therapeutic field for a hypnotic. The Council also declared the following statement improbable, and contrary to the evidence obtained by the referee:

“In dogs, the increase of dosage beyond the therapeutic dose to the
point of death is decidedly in favor of Dial ‘Ciba,’ which required
a larger dose [than diethylbarbituric acid] to produce death.”

The referee’s experiments on cats show that Dial “Ciba” is several times as toxic as hydrated chloral, and more than twice as toxic as diethylbarbituric acid (barbital).

Since the circular to which objection was made in 1918 was still being sent out in December, 1919, the Council held Dial “Ciba” inadmissible to N. N. R. and voted that report of its action in the matter be authorized for publication. The Council further directed that Dial “Ciba” be included with Articles Described but Not Accepted.--(_From The Journal A. M. A., Jan. 24, 1920._)

APOTHESINE

Report of the Council on Pharmacy and Chemistry

Apothesine is a synthetic drug for producing local anesthesia, made by Parke, Davis & Company. In the fall of 1917 the Council wrote to Parke, Davis & Company offering its aid in establishing the identity, purity and therapeutic efficiency of this synthetic local anesthetic with the ultimate object of accepting the product for inclusion in New and Nonofficial Remedies should the facts warrant such acceptance. The Council’s letter was never acknowledged. After Apothesine was put on the market the Council desired to accept it for inclusion in New and Nonofficial Remedies but, unfortunately, was unable to do so because some of the claims made for the product were not justified by acceptable evidence. The manufacturers were notified of the Council’s desire to admit this product to N. N. R. and the wish was expressed that the company would either so modify its claims as to make the product acceptable under the Council’s rules or else would submit evidence to the Council in proof of the claims made and thus permit the Council to revise its conclusions. Parke, Davis & Company were, apparently, either unwilling or unable to submit evidence that would sustain their claims; neither did they offer to modify the claims themselves. The product, therefore, is ineligible to inclusion in New and Nonofficial Remedies; it will, however, be listed in the “Described But Not Accepted” department of New and Nonofficial Remedies. The report on Apothesine that follows has been authorized for publication.

W. A. Puckner, Secretary.

Apothesine, “the hydrochlorid of diethyl-amino-propyl-cinnamate,” is an efficient local anesthetic. It belongs to the procain rather than to the cocain type, that is, it belongs to that type which, while effective for injection anesthesia (especially when combined with epinephrin) is relatively inefficient when applied to mucous membranes. Apothesine may also be used for spinal anesthesia. Its absolute toxicity is less than that of cocain (as 20 is to 15, see table below) but about twice that of procain (as 20 is to 40, see table below). It is non-irritant, is easily soluble and makes a stable solution so that it may readily be sterilized.

The Council took exception to certain claims made by Parke, Davis & Company for their product on the ground that these claims were not supported by acceptable scientific evidence. One of the claims was that Apothesine is applicable in any case in which any other local anesthetic is used. This statement, made in many advertisements, is distinctly misleading as used. When applied to mucous membranes Apothesine is far inferior to cocain and to some other local anesthetics, yet the claim obviously suggests that Apothesine is an efficient substitute for any local anesthetic.

The manufacturers claimed, too, that Apothesine is as potent as cocain. The claim would lead the physician to think that Apothesine had the same anesthetic potency as cocain in solution of equal strength. This statement, so far as it refers to the drug when applied to mucous membranes, is not in accord with the facts and is true for injection anesthesia only when stronger solutions are used. The only support for the claim of equal efficiency appears to be the experiments with intracutaneous injections made by H. C. Hamilton[130] in Parke, Davis & Company’s laboratory. These differed considerably from the results of Sollmann.[131] A further series of experiments were made by Sollmann to compare still further the diverse results previously reported by him and Hamilton. The latest series, while showing considerable variations in the susceptibility of different skin areas, especially toward Apothesine, demonstrated in every case that the efficiency of Apothesine is unmistakably lower than that of cocain, being at best one half. The series also showed that the potency of Apothesine was never greater than procain and averaged considerably below it.

[130] The Comparative Values of Some Local Anesthetics by H. C. Hamilton, Detroit, Mich., from the Research Laboratory of Parke, Davis & Co., J. Lab. & Clin. M. =4=:60 (Nov.) 1918.

[131] Comparative Efficiency of Local Anesthetics, V, by T. Sollmann, from the Pharmacological Laboratory of the School of Medicine, Western Reserve University, J. Pharmacol. & Exper. Therap. =11=:69 (Feb.) 1918.

Another claim made for Apothesine which the Council holds is not supported by evidence is that of superior safety. This claim is made on the basis of hypodermic injections in guinea-pigs carried out in the laboratory of Parke, Davis & Company. Such experiments prove little because of the fact--well known to laboratory workers--that the use of rodents in toxicity tests made by injecting a drug into the subcutaneous tissues does not give a reliable index of the relative toxicity of such a drug for man. This is due partly to the peculiar resistance of rodents to poisons and partly to the great importance of the rate of absorption. The organism destroys most local anesthetics so rapidly that the rate of absorption is more important than the absolute dose. The absorption from hypodermic injections into guinea-pigs differs, of course, from that in clinical accidents, especially where the drug has been applied to mucous membranes. One cannot, therefore, reliably estimate the degree of clinical danger on animals.

It has been shown that when toxicity tests of local anesthetics are made on cats these animals seem to respond to the drugs in a manner more closely approximating humans and it is a suggestive fact that the more toxic of local anesthetics, as shown by tests on cats, have been found the most dangerous in clinical use. The _absolute_ toxicity of Apothesine has been measured by Eggleston and Hatcher[132] by the intravenous injection in cats. The fatal doses, in terms of milligrams per kilogram ranged as follows:

Alypin, Holocain 10
Beta Eucain 12.5
Cocain 15
Apothesine 20
Tropacocain 20-25
Stovain 25-30
Nirvanin 30-35
Procain 40-45

[132] A Further Contribution to the Pharmacology of the Local Anesthetics by Eggleston and Hatcher, from the Department of Pharmacology, Cornell University Medical College, New York City, J. Pharmacol. & Exper. Therap. =13=:433 (Aug.) 1919.

The _absolute_ toxicity of Apothesine is, therefore, only a little lower than that of cocain, and is twice as great as that of procain. The _clinical_ dangers cannot be predicted by either method, since clinical accidents depend, in most instances, on idiosyncrasies, or the technic of application.--(_From The Journal A. M. A., Jan. 24, 1920._)

EUMICTINE

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below. This report declares “Eumictine” ineligible for New and Nonofficial Remedies because (1) it conflicts with Rule 10 in that it is unscientific, (2) it conflicts with Rule 6 in that it is sold under unwarranted therapeutic claims, (3) it conflicts with Rule 4 against indirect advertising to the public in that the name “Eumictine” is blown in the bottle for the obvious purpose of bringing the product to the attention of the public when it is prescribed in the original package, and (4) because the name is therapeutically suggestive and not in any way descriptive of its composition.

W. A. Puckner, Secretary.

Eumictine is a preparation from the laboratory of Maurice Le Prince, Paris, France, and is marketed in this country by George J. Wallau, Inc., New York. It is claimed that the product is “a balsamo-antiseptic preparation composed of Santalol, Salol, and Hexamethylene-Tetramine, in the form of gluten-coated capsules.” Nowhere in the advertising are the amounts of the ingredients given. According to the American agent, however, “each capsule is supposed to contain 20 centigrams of Santalol, 5 centigrams of Salol, 5 centigrams of Hexamethylene-Tetramine.”

Eumictine is advised “in treating genito-urinary diseases (urethritis, cystitis, prostatitis, pyelitis, etc.).” It is claimed to be “both an antiphlogistic modifying agent, a well-tolerated diuretic” which “may be administered for long periods without ill effects.”

The Council declares Eumictine ineligible for New and Nonofficial Remedies because it is exploited in conflict with the following rules:

It is unscientific (Rule 10). Eumictine is composed of hexamethylenamin, salol and sanalol in fixed proportions. Hexamethylenamin may serve a useful purpose in some forms of infection of the urinary tract, but neither it nor salol is of any considerable value in gonorrhea. It is now known that the balsamic preparations, formerly so widely used, do not have the curative effects in gonorrhea and associated conditions that used to be ascribed to them. To combine three substances, none of which has any distinct therapeutic value in the conditions for which Eumictine is proposed, does not enhance their value. There is nothing original in the combination used in Eumictine, or in the manner of dispensing it.

It is sold under unwarranted therapeutic claims (Rule 6). These claims are made not only for the components of Eumictine but for the combination itself. Though santalol has certain advantages over the somewhat variable oil of santal and other balsamic resins, it is not true that santalol “does not cause congestion of the renal epithelium” or that it does not “produce exanthema as do copaiba, cubebs, and the ordinary santal oil.” It is not true that salol is “devoid of toxicity.” Neither is it correct to say that salol “asepticizes and disinfects the bladder, the prostate and the urethra.” The claim that hexamethylenamin “is of value when any acute symptoms or tendency to inflammation subsist” is not justified. The claim that hexamethylenamin “renders soluble the uric acid and urates” is also without foundation. The following paragraph is characteristic of the claims made for Eumictine:

“Anti-gonorrhoic by its Santalol, diuretic, urolytic and analgetic
by its hexamethylenetetramin (Urotropin) antiseptic and antipyretic
by its Salol, Eumictine represents a real therapeutic advance in
the scientific treatment of diseases of the urinary passages.”

Instead of being “a real therapeutic advance” in the treatment of diseases of the urinary passages, Eumictine presents one of the complex combinations that have long retarded the scientific treatment of these diseases. Eumictine also conflicts with Rules 4 and 8 of the Council.--(_From The Journal A. M. A. Feb. 21, 1920._)

PLATT’S CHLORIDES

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on “Platt’s Chlorides.” It also declares the preparation inadmissible to New and Nonofficial Remedies because its composition is uncertain and indefinite and because the claims made for it are exaggerated and misleading.

W. A. Puckner, Secretary

“Platt’s Chlorides,” marketed by Henry B. Platt, New York, is sold as a disinfectant and germicide. Only incomplete and contradictory statements have been made in regard to its composition. Many years ago (about 1899) the composition of Platt’s Chlorides was given as “The Chlorids of Zn 40 per cent., Pb 20, Ca 15, Al 15, Mg 5, K 5.” The statement that the preparation contained 20 per cent. of lead chlorid is interesting, in view of the fact that lead chlorid is soluble in water at ordinary temperatures to the extent of less than 1 per cent. In a booklet, also issued a number of years ago, the following “Formula of Platt’s Chlorides” was given:

“A saturated solution of Metallic Chlorids combined in the
following proportions:

“Sol. Zinc Chlorid 40 per cent.
“Sol. Aluminum Chlorid 15 per cent.
“Sol. Lead Chlorid 20 per cent.
“Sol. Calcium Chlorid 15 per cent.
“Sol. Magnesium Chlorid 5 per cent.
“Sol. Potassium Chlorid 5 per cent.”

The label on a bottle purchased in 1911, describes Platt’s Chlorides as:

“A Highly Concentrated Solution of the Chlorids of Aluminum,
Calcium, Lead, Zinc, etc.”

The label of a bottle purchased in 1919 reads:

“Contains Inert Material: Water 84.0%. Sodium Chlorid 4.8%. Calcium
Chlorid 0.3%.”

This statement is obviously made to meet the requirements of the federal Insecticide Act. This law requires either that the identity and the amounts of potent ingredients in disinfecting preparations be declared or else that the percentage of the inert ingredients of such preparations be given. The omission from the label of all statements with regard to the potent ingredients of the preparation and the absence of such a statement in recent advertising matter suggests either that the older statements about its composition were false or else that the composition has been changed.

Tscheppe published (Pharmaceutische Rundschau =8=:109, 1890) an analysis of Platt’s Chlorides which has been quoted in other publications as indicating the composition of the preparation. He reported that he found each quart of the preparation to contain aluminum sulphate 6 ounces, zinc chlorid 1-1/3 ounces, sodium chlorid 2 ounces, calcium chlorid 3 ounces.

Some years ago (about 1911) the company made the following statement relative to the germicidal power (phenol co-efficient) of Platt’s Chlorides:

“... for some time the carbolic acid co-efficiency of our output
has been from 2.5 to 4.3, the average being about 3; namely about
three times stronger than pure carbolic acid.”

In 1912, the U. S. Public Health and Marine Hospital Service reported (_Bulletin_ 82, Public Health and Marine Hospital Service, p. 69) that the phenol coefficient of a sample of Platt’s Chlorides was so low that it could not be determined and also that the sample was found to contain some mercuric chlorid. In 1913, the North Dakota Agricultural Experiment Station reported (_Bulletin_, July, 1913, p. 292), that Platt’s Chlorides contained principally zinc chlorid, also some aluminum chlorid, calcium chlorid, and traces of mercuric chlorid. The phenol coefficient, determined by the Hygienic Laboratory method, was found to be 0.05.

The preceding suggests that the composition of Platt’s Chlorides had been changed (without notice to the consumer) and that it had been fortified by the addition of mercuric chlorid. Years ago part of the advertising of this product was a testimonial from a health official which declared that, for disinfection, “bichlorid of mercury is useless in disinfecting sputum or discharges from the bowels, being rendered inert by the albumin present” and it lauded Platt’s Chlorides as devoid of such drawbacks.

RECENT ANALYSES OF PLATT’S CHLORIDES

To determine the present composition of Platt’s Chlorides and to compare it with that sold formerly, the A. M. A. Chemical Laboratory has made an analysis of a specimen purchased in 1919 and also of one purchased in 1911 and since kept unopened in the files of the Council on Pharmacy and Chemistry. The following table contains the results of these analyses (all quantities given are Gm. per 100 c.c.):

1911 SPECIMEN 1919 SPECIMEN

Color Colorless Straw Color
Odor None None
Specific Gravity at 25 Cc. 1.1229 1.1313
Total Solids (residue at 100 Cc.) 16.49 18.33
Chlorid (Cl-) 7.60 10.74
Sulphate (SO₄--)  1.11 .16
Aluminum (Al+++) .22 .90
Calcium (Ca++) .19 .13
Zinc (Zn++) 5.11 3.93
Lead (Pb++) .046 Traces
Mercury (Hg++) .. .0086
Sodium (Na+) 1.01 1.39

These quantities transposed to hypothetical combinations would indicate that Platt’s Chlorides has the following composition:

1911 Specimen 1919 Specimen

Aluminum Sulphate 1.32 .18
Aluminum Chlorid .07 4.29
Calcium Chlorid .54 .37
Zinc Chlorid 10.66 8.19
Lead Chlorid .06 Traces
Mercury Chlorid .. .0116
Sodium Chlorid 2.57 4.81
Hydrogen Chlorid .43 None

In the past, the advertising has suggested, more or less directly, that, as chlorinated lime (bleaching powder) may be made to give off chlorin gas which disinfects, so the air in a room may be disinfected by evaporating Platt’s Chlorides. Thus the label of the 1911 specimen contains the following:

“FOR STORE ROOMS, Refrigerators, and Closets, keep a sponge
saturated with the pure liquid in a saucer on an upper shelf.”

On the label of the 1919 specimen, the statement reads:

“REFRIGERATORS AND STOREROOMS--As a disinfectant wash regularly
with one part Chlorides to eight of water. As a deodorant, keep in
an open vessel a sponge or cloth saturated with the Chlorides full
strength.”

That the owner of Platt’s Chlorides really believes that the vapors of the preparation have disinfecting properties is seen from a letter over the name of Henry B. Platt printed in the New York _Tribune_ in 1916. This read, in part:

“... by keeping in a dish or saucer on radiators Platt’s Chlorides
diluted one-half, the hot solution will evaporate and purify the
air, thus destroying the grip germ which is the cause of all the
trouble.”

From the analysis of Platt’s Chlorides, it is evident that when the preparation is evaporated, water vapor only escapes.[133] Whatever disinfecting or germicidal action the preparation may possess is exercised only when the solution is brought in direct contact with the substance to be disinfected.

[133] It is well known that when a solution of mercuric chlorid in water is evaporated, mercuric chlorid passes off with the water vapors, but under any condition the amount is but a fraction of the whole. As in Platt’s Chlorides other metallic chlorids are present, the formation of complex mercuric compounds which is bound to have occurred, should retard or prevent the volatilization of mercuric chlorid. That this actually occurs was confirmed by the following experiment: When 1 gm. mercuric chlorid was dissolved in 1 liter of water and the solution distilled, the distillate contained a very small amount of mercury. Then the experiment was repeated after adding sodium chlorid to the solution to simulate the conditions in Platt’s Chlorides. In this case no mercury was found in the distillate. Even were all the mercury in a bottle of Platt’s Chlorides volatilized in a room 10 by 12 by 9 feet, this would be equivalent to only about 1/500 grain mercuric chlorid per cubic foot.

The aluminum and zinc salts present may be useful as deodorants but they are not effective as germicides. The presence of mercuric chlorid in a concentration of 1 to 10,000 is hardly to be considered as materially increasing the efficiency. The directions recommend the use of a mixture of 1 part of Platt’s Chlorides to 10 parts of water for rinsing the hands, and a mixture of 1 part to 4 parts of water for the disinfection of discharges. It is further stated that 1 quart makes 2 gallons sufficiently strong for general use. It is evident that such dilutions decrease considerably the feeble germicidal action of the original fluid.--(_From The Journal A. M. A., March 27, 1920._)

ANTI-TUBERCULOUS LYMPH COMPOUND (SWEENY) AND ANTI-SYPHILITIC
COMPOUND (SWEENY)

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the reports which appear below, declaring Anti-Tuberculous Lymph Compound (Sweeny) and Anti-Syphilitic Compound (Sweeny) ineligible for New and Nonofficial Remedies.

W. A. Puckner, Secretary.

Anti-Tuberculous Lymph Compound (Sweeny)

“Anti-Tuberculous Lymph Compound (Sweeny)” is put out by the National Laboratories of Pittsburgh, Dr. Gilliford B. Sweeny, “Medical Director.” Sweeny has claimed at different times that he became interested in the subject of von Behring’s efforts to immunize cattle to tuberculosis at a time when he was an assistant in von Behring’s laboratory. He claims to have conceived the idea while there of transferring bovine immunity to tuberculosis to the human subject and later to have evolved his “treatment” at the Pasteur Institute in Paris.

Just how Anti-Tuberculous Lymph Compound is made today is not stated--at least so far as one is able to learn from recent advertising. Some years ago Sweeny declared that his “Anti-Tubercular Lymph” (as it was then called) was derived from a bullock which had been immunized to tuberculosis. Then:

“The immunized animal having been slaughtered, the contents of the
lymph reservoirs are carefully collected and an aqueous extract is
made from the grey cerebral substance, spinal cord and the lymph
glands. It is then filtered under high pressure and de-albuminized
by succussion. To this, the lymph, together with a definite
proportion (50 per cent.), of the naturally phosphorized brain fats
is added, with a small amount of chloride of gold (about 1-60 gr.
to the dose), the latter as a preservative.”

It is a fair assumption that however the preparation may have been made originally, it is not now made in such a manner as to bring it under the federal laws governing the preparation of serums and similar preparations. The claims made for Anti-Tuberculous Lymph Compound are of the usual uncritical and unscientific type. Mainly, of course, they are of the testimonial class. The physician is told that the preparation has been carefully tested by men whose judgment is worthy of consideration; that the verdict has been altogether favorable to the “Compound.” Thus:

“... the remedy was submitted to a selected body of skilled
physicians, recognized for their skill and care in making
therapeutic observations. These men represented widely varying
conditions, climatic and otherwise. Those who said ten years ago
that Anti-Tuberculous Lymph Compound has a specific immunizing
influence upon the tuberculosis patient, find the same to be true
today.”

Careful reading of the matter just quoted will reveal its ambiguity and inherent lack of frankness. The inference conveyed is that the “selected body of skilled physicians” have unqualifiedly endorsed Anti-Tuberculous Lymph Compound (Sweeny)--but it does not say so!

It is the history of all such preparations, introduced to the medical profession with the usual blare of trumpets, that a certain number of favorable testimonials can be obtained. It is also the history of such products that one has but to wait a few years and the physicians who had written most enthusiastically regarding the preparation--in the first flush of their optimism following its use and the perusal of the manufacturers’ literature--will acknowledge that they were mistaken in their original estimate and are no longer using the agent. In this connection an investigation of some of the old testimonials for Anti-Tuberculous Lymph Compound by the Propaganda department of The Journal is instructive.

In a somewhat elaborate booklet published in 1907 by Sweeny, an Indiana physician was said to have reported favorable results following the administration of the “lymph.” A letter written to this physician in October, 1919, asking for his present opinion on the product brought this reply, in part:

“... it being twelve years since using the serum and no reference
or repeated orders since should surely suffice as evidence of my
lack of faith in the serum....”

An Illinois physician was reported in the same booklet to have described a case of a young man with an active tuberculosis, who was given injections of the “lymph” in February, 1907. The patient, it was claimed, showed immediate improvement and the Sweeny booklet (published in August, 1907) stated that “improvement in this case continued and terminated in complete recovery.” A letter written to the physician in October, 1919, brought out the fact that the young man in question, after receiving “Anti-Tuberculous Lymph Compound” and _other treatment_ was removed “on a stretcher” “to New Mexico, where he remained for three or four years” and recovered. The doctor adds:

“I do not think that the Anti-Tuberculous Lymph had anything to
do with the man’s recovery, although I realize the difficulty of
definitely analyzing just what did effect the cure. I did since
that time use that preparation in several other cases without
beneficial results so that I gave it up a good many years ago
adding it to that large heap of pharmaceutical material ‘weighed
and found wanting.’”

A physician in Texas also reported in the 1907 booklet as having had very satisfactory results with the Anti-Tuberculous Lymph Compound in one case of pulmonary tuberculosis was written to in October, 1919. He replied:

“I will state that subsequent use of this compound did not bear out
the apparent good results from its use in the first case or two.”

In a “Bulletin” issued by the Sweeny concern in 1912, a Pennsylvania physician was quoted as having treated three cases with Anti-Tuberculin Lymph Compound with resultant cures. This physician was written to in October, 1919, and he replied:

“I have no knowledge of the use of my name by any Pittsburgh
concern and know nothing of a lymph of the name of Sweeny; neither
do I recollect ever curing three cases of tuberculosis with any
lymph.”

The same “Bulletin” quoted the alleged statement by a Delaware physician to the effect that he believed Anti-Tuberculous Lymph Compound to be the most successful treatment of tuberculosis extant. This in 1912. To an inquiry sent in October, 1919, this physician briefly replied:

“Am not using it now.”

The result of the Propaganda department’s questionnaire was what might have been expected. Every physician who answered the inquiry regarding his previous and present opinions of Anti-Tuberculous Lymph Compound (Sweeny) declared, in effect, that he had long since ceased to have faith in its value or efficacy.

According to claims made in Sweeny literature, “Anti-Tuberculous Lymph Compound exercises its immunizing power through a specific action upon the blood cells.” The statement that “it destroys the tuberculosis germ when this is present in the system of the patient” is untrue. The facts are, no serum or lymph has thus far been proved to have any value in the treatment of tuberculosis even when fortified by “a small proportion of chloride of gold and soda” as one circular tells us the “lymph” is. In spite of research by competent investigators, we are still without any aid in the form of a serum in the treatment of tuberculosis.

Anti-Tuberculous Lymph Compound (Sweeny) is one of those preparations that need no elaborate laboratory tests, nor even exact therapeutic research, to convince any clear-thinking person that it is patently and obviously worthless. One would hesitate before asking any reputable clinician to test a preparation of this sort. It is a constant source of surprise that some physicians allow themselves to be persuaded by advertising literature that is obviously uncritical and unscientific, to use preparations which have no more reasonable foundation than this one.

The Council declares Anti-Tuberculous Lymph Compound (Sweeny) not acceptable for New and Nonofficial Remedies.

Anti-Syphilitic Compound (Sweeny)

This preparation also is made by or under the direction of the same Dr. Gilliford B. Sweeny whose researches (?) led to the production and evolution of the Anti-Tuberculous Lymph Compound (Sweeny). According to the data at hand, this preparation is made by suspending benzoate of mercury in lymph from the bullock. Case reports are given of alleged cures of syphilis after two months of treatment; indeed, the circular exploiting the agent makes the statement that it is seldom necessary to continue the treatment beyond two months, which, if one chose to be credulous, would indicate extraordinary power for the mercury.

Mercury of course has a proper place in the treatment of syphilis, but that any physician could be induced to place his trust in this preparation is almost unthinkable though testimonials--which the “National Laboratories” claim to have received from physicians--are published. They all stamp the writers as not only gullible but also incompetent. The tenor of the claims is on a par with those made for the Anti-Tuberculous Lymph Compound; they do not justify the time required for detailed consideration.

The Council declares Anti-Syphilitic Lymph Compound (Sweeny) not acceptable for N. N. R.--(_From The Journal A. M. A., April 3, 1920._)

SYRUP LEPTINOL (FORMERLY SYRUP BALSAMEA)

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on “Syrup Leptinol” (formerly “Syrup Balsamea”). The product is inadmissible to “New and Nonofficial Remedies,” first, because the manufacturers fail to give the profession information regarding either the amount of the potent ingredient or the method of determining its identity and uniformity; second, because of the unwarranted recommendation for its use in such infectious diseases as pneumonia and epidemic influenza and for lack of satisfactory supporting evidence of its alleged therapeutic efficacy in other diseases and, third, because the recommendations for its use appearing on and in the trade package constitute an indirect advertisement to the public.

W. A. Puckner, Secretary.

Syrup Leptinol is sold by the Balsamea Co. of San Francisco. It was first introduced as Syrup Balsamea. In recent advertising, Syrup Leptinol is also referred to simply as “Leptinol.”