Volume 1 / Part 1 — FOREWORD (continued 8)

Red Bone-Marrow

Red bone-marrow consists largely (more than 90 per cent.) of fat. In new-born animals a third or more of this fat consists of lecithin. The marrow of the bones of new-born animals contains iron (up to 1 per cent. or more) in various forms of organic combination. Both lecithin and iron decrease rapidly in the first weeks after birth. The commercial preparations contain very variable amounts of these constituents.

Actions and Uses.—Red bone-marrow is supposed to stimulate the formation of red blood corpuscles; whatever action it may have in this direction is probably due largely to the iron and lecithin which it contains.

It is said to be useful in simple and pernicious anemias.

Thymus Gland

Little is known as to the functions of the thymus, but it is believed to have an important relation to growth. There also seems to be some relation between the thymus and thyroid, for the former is frequently abnormal in diseases involving the latter (hyperthyroidism).

The use of thymus is purely empirical. It has been employed in the treatment of hyperthyroidism, rickets, tuberculosis, hemophilia, and infantile marasmus and atrophy; its use in the latter conditions is said to be the most promising. It is claimed on very doubtful grounds to exert a somewhat favorable effect in certain cases of cancer.—(From Reports of Council on Pharmacy and Chemistry, 1918, p. 69)

PIPERAZINE AND LYCETOL OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The following report explaining the omission from New and Non­official Remedies of Piperazine and Lycetol has been authorized for publication.

W. A. Puckner, Secretary.

Piperazine (diethylenediamene) and Lycetol (a methyl derivative of diethylenediamene) were accepted for New and Non­official Remedies in 1906. Both Piperazine and Lycetol were asserted to be efficient uric acid solvents and efficacious remedies in the treatment of gout and rheumatism. These products have been retained until now because there was no investigation which definitely showed their uselessness as uric acid solvents, though their use is generally admitted to have been disappointing.

From an exhaustive and critical study of the available evidence, Hanzlik (Jour. Lab. & Clin. Med., February, 1917) concluded that scientific evidence, though limited, and clinical opinion indicate that Piperazine is valueless in gout and that there is sufficient scientific evidence to indicate the worthlessness of Lycetol.

The referee in charge of Piperazine and Lycetol recommended that these products be omitted from New and Non­official Remedies for the reason that they have been sufficiently tried to justify the conclusion that they are not of value. The period of acceptance having expired, the Council directed that Piperazine and Piperazine Tablets (The Bayer Company, Inc.) and Lycetol (The Bayer Company, Inc.) be omitted from New and Non­official Remedies.—(From Reports of Council on Pharmacy and Chemistry, 1918, p. 70.)

STANOLIND LIQUID PARAFFIN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

As explained in the report which follows, “Stanolind Liquid Paraffin” was omitted from New and Non­official Remedies at the request of the proprietors. Announcement of this omission was made in the preface to New and Non­official Remedies, 1918, but publication of the Council’s report was postponed pending actual conflict with the rules. The Council now authorizes publication of the report because a circular indirectly advertising the product to the public was found enclosed with the trade package of Stanolind Liquid Paraffin.

W. A. Puckner, Secretary.

Stanolind Liquid Paraffin was admitted to New and Non­official Remedies in 1916, when its method of marketing conformed to the rules of the Council. This brand of liquid petrolatum, by action of the Council, has been omitted from New and Non­official Remedies on request of the Standard Oil Company of Indiana, its manufacturer, who wrote to the Secretary of the Council stating that:

“In order that our facilities for the manufacture of this oil shall be constantly engaged, it will be necessary for us to find sales on a larger scale than in the past. To do this under our present advertising and marketing arrangement we feel will be impossible.”

This letter, in addition, suggested “that physicians are not prescribing Stanolind Liquid Paraffin in any considerable proportion of their orders” and “that the situation which now confronts us would not be materially helped if Stanolind was specified in all such prescriptions.” Further, the Council is asked to consider whether it “might be willing to declare this preparation as not a Council product,” on the alleged grounds that “liquid paraffin is not medicinal in its action and passes through the digestive tract in practically unaltered condition.”

The Council holds that Stanolind Liquid Paraffin is a drug, and that, therefore, its direct advertising to the public is in contravention of the Council’s rules. Constipation should be treated by dietary and hygienic means. Evacuants are only temporary measures. Liquid petrolatum is medicinal; it greatly modifies the intestinal flora; it acts as a lubricant and emollient; it modifies the absorptive powers of the intestinal mucous membrane; it is capable of influencing the digestion of fats. In short, liquid petrolatum, being a drug, its indiscriminate and excessive use should not be encouraged.—(From Reports of Council on Pharmacy and Chemistry, 1918, p. 72)

WESTERFIELD’S DIGITALIS TABLETS

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its publication.

W. A. Puckner, Secretary.

Westerfield’s Digitalis Tablets (The Westerfield Pharmacal Co., Dayton, Ohio) are claimed to represent a fat free tincture of digitalis and to be “enteric coated.” It is claimed that because of this coating these tablets pass the stomach unchanged and dissolve in the intestine, and that this obviates any possibility of gastric disturbance.

The circular which sets forth the asserted advantages of the tablets states that digitalis contains a fat which is an irritant to the gastric membrane. It also contains the following:

“We feel no hesitation in saying that if this remedy is given a fair trial where it is properly indicated, the result obtained will be a gratifying surprise.

“It is a common expression from physicians who have tried this remedy to say, ‘Surely I have never used Digitalis before.’ ”

If these quotations mean anything, they imply that these tablets present a distinct advance in digitalis therapy. There is no warrant for such a claim. The statement with reference to the occurrence of an oil in digitalis is partly false and partly misleading. Tincture of digitalis, which the tablets are claimed to represent, is fat free; the fixed oil that is present in the drug is not soluble in 70 per cent. alcohol, the menstruum used for the preparation of the official tincture of digitalis. Furthermore, a fairly large amount of this oil (such as is present in 100 therapeutic doses of the drug) is incapable of causing gastric disturbance. Gastric disturbance is a side action that is inseparable from slight overdosage with all true digitalis bodies and is not in any way due to local gastric action. The claim that such action is prevented by the use of enteric pills or tablets is obviously false and misleading.

The alleged “common expression from physicians who have tried this remedy” does not constitute acceptable evidence of the value of the preparation.

The Council declared Westerfield’s Digitalis Tablets inadmissible to New and Non­official Remedies because unwarranted therapeutic claims are made for this product.

When the preceding report was submitted to the Westerfield Pharmacal Co., a reply was received indicating that the firm did not know that progressive manufacturers had discontinued the claim that “fat free” digitalis preparations were devoid of gastric effects. It also submitted a revised circular, which, however, reiterated the claim that the tablet presented a distinct advance in digitalis therapy in that it was “fat free,” and coated to prevent disintegration in the stomach.

Since tincture of digitalis and extract of digitalis are practically devoid of fatty material, and since it is now well known that the fat does not cause gastric disturbance and that therapeutic doses of digitalis do not exert a local irritant action on the stomach, the manufacturer’s product and the claims made for it merely tend to perpetuate old errors.

The Council declared Westerfield’s Digitalis Tablets inadmissible to New and Non­official Remedies on the ground that this presents an unessential modification of pills of an official substance. It directed publication of its report with this explanation.—(From Reports of Council on Pharmacy and Chemistry, 1918, p. 75)

XEROFORM-HEYDEN AND BISMUTH TRI­BROM­PHENATE-MERCK OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Bismuth Tri­brom­phenate-Merck and Xeroform-Heyden. These two products were found not to comply with the standards for bismuth tri­brom­phenate adopted for New and Non­official Remedies, and hence could not be retained. As the manufacturers of both products announce that efforts toward the production of a satisfactory product are continued, the omission of the two brands is without prejudice to their reacceptance when a satisfactory product becomes available.

W. A. Puckner, Secretary.

The referee in charge of bismuth preparations submitted the following report of the A. M. A. Chemical Laboratory which shows that Xeroform-Heyden and Bismuth Tri­brom­phenate-Merck do not comply with the adopted standards for bismuth tri­brom­phenate.

Some time ago a request was received from the Medical Section of the National Council of Defense for a report on a brand of bismuth tri­brom­phenate. In accordance with this request the firm’s product was examined, and at the same time and for comparison, an examination was also made of a specimen of bismuth tri­brom­phenate received from Merck and Company, October, 1915, and of another specimen of bismuth tri­brom­phenate “Xeroform-Heyden” obtained from the Chicago branch of the Heyden Chemical Works in April, 1918.

The examination brought out that the bismuth tri­brom­phenate submitted to the national Council of Defense contained a large amount of uncombined tri­brom­phenol, while the specimen of Xeroform-Heyden contained an excessive quantity of bismuth.

When the latter finding was submitted to the Heyden Chemical Works, the firm stated: “The product had to be made in this country after importations from Europe became impossible and the first lots were not fully up to the standard ...” The firm stated that it could now furnish a product which it considered fully equal to that which was previously imported, and offered to submit “samples of the new material.”

Having been requested to do so, a specimen of Xeroform-Heyden was received from the Heyden Chemical Works, New York. This and a second specimen, purchased from a Chicago wholesale drug house, were examined. Whereas the standards for bismuth tri­brom­phenate which had been formulated by the Laboratory and accepted by the Heyden Chemical Works required that the product should contain from 40 to 49 per cent. of bismuth and contain not more than 3.3 per cent. of uncombined tri­brom­phenol, the specimen purchased in Chicago contained 67.7 per cent. of bismuth, while the specimen received direct from the Heyden Chemical Works contained 24 per cent. of uncombined tri­brom­phenol. When this result was reported to the Heyden Chemical Works, the firm replied:

“It seems that we are not yet in a position to supply a product that answers a uniform standard and that we have to continue our efforts in this direction.

“We will take this matter up with you again as soon as we have been successful ...”

At the time when the preceding examination was being made, bismuth tri­brom­phenate-Merck could not be obtained from the Chicago wholesale houses. A request sent to Merck and Company for a specimen of the market supply brought the information that the product was temporarily unavailable. Though unable to supply the product, the firm gave valuable advice for a revision of the somewhat loosely drawn tests for bismuth tri­brom­phenate in New and Non­official Remedies, 1918.

Recently (November, 1918) Merck and Company sent a specimen of its product labeled “Bismuth Tri­brom­phenate-Merck” “Merck and Company, New York, Distributors and Guarantors,” and wrote “... You will notice this sample conforms in nearly all details to the tests we submitted with our letter of June 4th. We have been able to produce better goods, but just at present unsatisfactory starting material confronts us. The sample conforms to N. N. R., 1918, but will not meet the test for uncombined tri­brom­phenol submitted by you in your letter of September 4th ...”

Examination of the specimen demonstrated that it was soluble to a considerable extent in alcohol (the N. N. R., 1918, description provides that it should be only slightly soluble in alcohol) and according to the standards adopted for New and Non­official Remedies, 1919, contains 18 per cent. uncombined tri­brom­phenol (more than five times the permitted amount).

In view of the Laboratory’s report, the referee recommended that the acceptance of Xeroform-Heyden and Bismuth Tri­brom­phenate-Merck be withdrawn, without prejudice to their reinstatement when satisfactory products are again offered for sale. The Council adopted the recommendation of the referee, and accordingly Xeroform-Heyden and Bismuth Tri­brom­phenate-Merck are omitted from New and Non­official Remedies, 1919.

When the Laboratory’s findings with regard to Xeroform-Heyden and the action of the Council deleting the article from New and Non­official Remedies was reported to the Heyden Chemical Works, the firm expressed regret that efforts to produce a product equal to that formerly obtained from Germany had so far not been successful and announced that it had decided to withdraw Xeroform-Heyden from the market for the present.

When Merck and Company was advised in regard to the report of the Laboratory and the Council’s action, this firm questioned the feasibility of producing a product meeting the Council’s standards and suggested that the test for free tri­brom­phenol be revised to permit as much as 15 per cent. of this constituent. When Merck and Company was reminded that its product, submitted in 1915, essentially complied with the adopted standards and that the estimate of the therapeutic value of bismuth tri­brom­phenate is based on a product essentially free from alcohol-soluble material, the firm replied:

“As stated in our letter of the 12th inst. we do not wish to market the chemical unless it meets all legitimate requirements of the physicians that use it. If, therefore, your standard proves to be good and it is commercially possible to make supplies conforming to it, we shall do so. We shall discontinue the article unless it is of suitable quality.”

—(From Reports of Council on Pharmacy and Chemistry, 1918, p. 76.)

CREAM OF MUSTARD REFUSED RECOGNITION

Report of the Council on Pharmacy and Chemistry

Cream of Mustard, The Cream of Mustard Co., South Norwalk, Conn., is said to be made by mixing 2 drachms of oil of mustard and 2 drachms of oil of turpentine with one pound of white petrolatum. According to the label it is “for Tonsillitis, Rheumatism, Sore Muscles, Croup, Pleurisy, Frosted Feet, Sore Throat, Neuralgia, Sprains, Bronchitis, Headache, Chilblains, Stiff Neck, Congestion, Bruises, Asthma, Lumbago, Pains and Aches, Colds in Chest.”

The Council refused recognition to Cream of Mustard:

Because it is a simple pharmaceutical mixture of well-known ingredients and has no advantage over established rubefacients which every physician knows how to prescribe and every pharmacist to compound. Incidentally, the name “Cream of Mustard” is misleading and not descriptive of the composition of this pharmaceutical of oils of mustard and turpentine.—(From Reports of Council on Pharmacy and Chemistry, 1918, p. 79)

“PLURIGLANDULAR” MIXTURES

Caps. Adreno-Spermin Comp., Caps. Antero-Pituitary Comp., Caps. Placento-Mammary Comp., Caps. Thyro-Ovarian Comp., Caps. Hepato-Splenic Comp., Caps. Pancreas Comp., and Caps. Thyroid Comp., Not Admitted to N. N. R.

Report of the Council on Pharmacy and Chemistry

After considering the evidence for the several “pluriglandular” mixtures described below, the Council declared them inadmissible to New and Non­official Remedies. The Council’s action was communicated to the manufacturer, Henry R. Harrower, in accordance with the usual procedure. After giving due consideration to the manufacturer’s reply the Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

With the offer “to supply you with as much literature as may be necessary and as little of the actual remedies as may be desired” if “the prospects for the inclusion of these formulas in N. N. R. are good,” Henry R. Harrower sent the Council a booklet descriptive of his preparations and labels for the following mixtures:

Caps. Adreno-Spermin Comp., each said to contain “Adrenal Gland (total) gr. ¹⁄₄, Thyroid Gland (U. S. P.) gr. ¹⁄₁₂, Spermin Extr. (from Gonads), Brain and Spinal Cord aa gr. 1, Calc. Glycero­phosphate q. s. ad gr. 5.”

Caps. Antero-Pituitary Comp., each said to contain “Anterior Pituitary Body gr. 2, Thymus Gland gr. 1, Thyroid Gland (U. S. P.) gr. ¹⁄₁₂, Calcium-phosphorus Comp. q. s. ad gr. 5.”

Caps. Placento-Mammary Co., each said to contain “Desiccated Placenta gr. 2, Mammary Substance gr. 1¹⁄₂, Pituitary Body (total) gr. ¹⁄₃, Calcium-phosphorus Comp. q. s. ad. gr. 5.”

Caps. Thyro-Ovarian Comp., each said to contain “Desic. Corpora Lutea Ovarian Substance gr. 2¹⁄₂, Thyroid Gland (U. S. P.) gr. ¹⁄₁₂, Pituitary Gland (total) gr. ¹⁄₈, Calcium-phosphorus Comp. q. s. ad gr. 5.”

Caps. Hepato-Splenic Comp., each said to contain “Liver Parenchyma, Spleen Substance aa gr. 2, Powd. Bile Salts gr. ¹⁄₂, Adreno-Spermin Co. (No. 1) gr. 1.”

Caps. Pancreas Comp., each said to contain “Adrenal Gland, Pituitary Gland (total) aa gr. ¹⁄₂, Ovarian Substance gr. 1, Pancreas Substance q. s. ad gr. 5.”

Caps. Thyroid Comp., each said to contain “Desic. Thyroid Gland (U. S. P.) gr. ¹⁄₈, Calcium-phosphorus Comp. q. s. ad gr. 5.”

The Council declared these preparations inadmissible to New and Non­official Remedies, for reasons which follow:

1. Each of the mixtures contains one ingredient or more, which is neither recognized in the U. S. Pharmacopeia nor admitted to New and Non­official Remedies, namely: “Spermin Extract,” “Brain,” “Spinal Cord,” “Desiccated Placenta,” “Liver Parenchyma,” “Spleen Substance,” “Pancreas Substance” and “Calcium Phosphorus Comp. (Each 100 gm. represents Magnes. Phos. 1; Calc. glycerophos. 4; Potas. bicarb. 15; Sod. bicarb. 22 and Sod. chlor. q. s.).” For obvious reasons the Council does not accept a mixture containing an indefinite ingredient and hence it would be necessary as a preliminary for the consideration of any one of the mixtures that their unofficial ingredients be made eligible for New and Non­official Remedies by the submission of evidence that such ingredient is of uniform composition and that it is thera­peutically valuable when given by mouth. There is no evidence that many of these organs have any value whatever when administered by the mouth or in any other way.

2. In the light of our knowledge the administration of gland mixtures in the host of conditions enumerated in the advertising circular is irrational and on a par with the use of the shotgun mixtures once in vogue.

Be it a pharmaceutical mixture, a “mixed” vaccine, or a “pluriglandular” product, the combination of two medicinal ingredients in a mixture must be considered contrary to rational therapy unless a good reason exists for such combination. Such mixtures are held in conflict with Rule 10 unless the manufacturer presents acceptable evidence for the value of his combination. A physician may prescribe any mixture which he considers indicated in a given case, but the marketing of mixtures of drugs in fixed proportions is in most instances irrational and a detriment to sound therapy.—(From The Journal A. M. A., Jan. 18, 1919)

CERELENE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report declaring Cerelene inadmissible to New and Non­official Remedies.

W. A. Puckner, Secretary.

Cerelene, a paraffin preparation for the treatment of burns, was submitted to the Council by the Holliday Laboratories, with the statement that it was composed of 84 per cent. paraffin, 15 per cent. myricyl palmitate, and 1 per cent. purified elemi gum to which is added oil of eucalyptus 2 per cent. and betanaphthol 0.25 per cent. It was explained:

“Myricyl Palmitate is a purified form of Beeswax, free from all impurities, acids, etc., which is solely manufactured by this Company....”

It was also stated that on “special order” Cerelene has been made containing oil of eucalyptus and resorcin, oil of eucalyptus and picric acid, and picric acid alone. The following report on the preparation was presented to the Council by the referee to whom Cerelene had been assigned:

Cerelene is another compound wax for the treatment of burns. According to the work of Sollmann (J. A. M. A., 68:1799, 1917) it is highly improbable that compound mixtures have any advantage over simple paraffin of low melting point. Cerelene must therefore be considered as an unessential modification of paraffin, and as in conflict with Rule 10; unless definite evidence of superiority is submitted. Cerelene mixtures containing medicinal ingredients also appear unscientific since the evidence that the ingredients do not leave the wax has not been successfully contradicted. Finally, the claims made for Cerelene are rather extreme, and would need some revision before they could be accepted.

The A. M. A. Chemical Laboratory reports:

The physical properties of Cerelene are as follows:

Melting point 50.0 C. by U. S. P. method.

Ductility limit30.5 C.

Plasticity limit26.4 C.

Not strong at38 C.

Adheres moderately well; detaches with “pulling.” On heating, readily loses eucalyptol, and a small amount of resinous substance forms in the bottom of the beaker. If Cerelene is heated to 145 C. and cooled, the resulting product no longer has the properties of the original Cerelene.

It is recommended that the preceding report be sent to the Holliday Laboratories, and that unless its superiority over simple paraffins is demonstrated and the unwarranted claims abandoned, Cerelene be declared inadmissible to New and Non­official Remedies for conflict with Rules 6 and 10.

This report was submitted to the Holliday Laboratories with the information that it had been adopted, Oct. 3, 1917. It was also explained that before Cerelene could be accepted, the unofficial and unstandardized constituent “myricyl palmitate” would have to be considered and accepted for New and Non­official Remedies since, for obvious reasons, the Council does not accept a preparation which contains an unofficial and unstandardized substance not in N. N. R.

The Holliday Laboratories acknowledged receipt of the Council’s report and asked that the matter be held in abeyance until the requested evidence had been obtained. Later the Council was advised that the advertising circulars for Cerelene had been withdrawn with the exception of one giving directions for its use. Five months later, the firm stated that experiments were being made “to determine the actual strength of Cerelene in comparison with other paraffin waxes....” Nothing further has been heard from the Holliday Laboratories and no reply has been received to an inquiry made Oct. 12, 1918. The Council therefore authorizes publication of its report declaring Cerelene inadmissible to New and Non­official Remedies.—(From the Journal A. M. A., Feb. 15, 1919).

COLLOSOL COCAINE NOT ADMITTED TO N. N. R

Report of the Council on Pharmacy and Chemistry

The report which appears below was adopted by the Council and sent to the Anglo-French Drug Co., Ltd., New York, for comment in December, 1918. No explanation has been received from the manufacturer. For the information of the profession the Council has now authorized publication of the report.

W. A. Puckner, Secretary.

“Collosol Cocaine” was submitted to the Council in October, 1918, by the Anglo-French Drug Co., Ltd., New York, under the claim that it was an “absolute colloid” and that it contained “1 per cent. cocain.” The label on the submitted specimen declares:

“Collosol Cocaine 1-100”

“... the Cocaine exists as the pure alkaloid in the Colloidal state—the condition in which it is isomorphic with the protein of the body fluids. The effect is more prolonged than that of a molecular Cocaine Solution and being non-toxic absorption presents no practical danger.”

The product was assigned to the Committee on Pharmacology for consideration. The following report was submitted and its adoption by the Council recommended by the committee:

“Collosol Cocaine” is said to be a colloidal form of cocain and is alleged to possess a remarkably low toxicity. The subjoined report of the A. M. A. Chemical Laboratory, however, shows that the preparation does not have the composition claimed for it and it is, in effect, misbranded. In fact, the English manufacturers concede that it is not an “absolute colloid” and that the declaration with regard to the percentage of cocain is incorrect.

It is recommended that, without considering other conflicts with the rules of the Council at this time, “Collosol Cocaine” be declared inadmissible to New and Non­official Remedies for conflict with Rule 1 which requires that the composition of an article must be correctly declared. The report of the A. M. A. Chemical Laboratory is appended.

REPORT OF THE A. M. A. CHEMICAL LABORATORY

Simpson, Hewlett and Eyre (Lancet, April 28, 1917, p. 660) reported “Collosol Cocaine” to be much less toxic than cocain. These writers, however, did not verify the statements as to the composition and in the light of subsequent chemical examination it is not to be wondered at that “Collosol Cocaine 1.0 per cent.” was much less toxic than a solution containing 1.0 per cent. of cocain hydrochlorid.

Barger, Dale and Durham report from the Department of Biochemistry and Pharmacology, Medical Research Committee (Lancet, Dec. 1, 1917, p. 825), that they examined “Collosol Cocaine” and found it to contain but 0.25 per cent. of cocain. They also found that the cocain was not present in a colloidal form. Discussing the low toxicity claimed by the manufacturers, these investigators state:

“In the samples which we examined the toxicity was, indeed, much lower than that of an ordinary 1 per cent. solution of a cocain salt; but the local anesthetic action was low to a corresponding degree, and both actions corresponded satisfactorily with the proportion of cocain chemically recoverable from the solution.”

Stroud, of the Crookes Laboratory (which manufactures the preparation), who apparently had been informed of this work in advance of publication, admits the correctness of it, and states (British Medical Journal, Nov. 24, 1918, p. 710) that “whilst the colloidal protective apparently absorbs a portion of the cocain, the remainder is found not to exhibit the attributes of a colloid,...”

The specimen of “Collosol Cocaine” submitted to the Council and labeled “Collosol Cocaine 1-100” was found to contain at most 0.4 per cent. cocain. The examination was made in accordance with the method used by Barger, Dale and Durham and calculated as cocain. This method, however, probably would not distinguish between cocain and basic decomposition products, but would include all as cocain in the amount found. The specimen of “Collosol Cocaine” examined was neutral or slightly acid, a fact which tends to confirm the conclusion of the British investigators that “Collosol Cocaine” contains cocain in noncolloidal form and precludes an increased physiologic effect due to alkalinity.

The Council adopted both the report submitted by the committee and that of the A. M. A. Laboratory and declared “Collosol Cocaine” inadmissible to New and Non­official Remedies.—(From The Journal A. M. A., April 12, 1919.)

CUPRASE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Cuprase, sold by the Anglo-French Drug Co., Ltd. The Council’s criticisms of the advertising claims were sent to the firm, December, 1918. The firm made no reply and essentially the same claims are contained in recent advertisements.

W. A. Puckner, Secretary.

“Cuprase” is now being advertised and sold in the United States by the Anglo-French Drug Co., Ltd., the firm which also markets it in England. It is said to be “prepared in the Laboratories of F. Ducatte, 8 Place de la Medeleine, Paris.” According to an advertising circular entitled “The Medical Treatment of Cancer” “Cuprase” is “chemical colloidal copper”; in another place it is “a colloidal copper hydroxid,” which is said to be obtained chemically by the reduction of salts of copper in the presence of albumosic acid.

A box (price $8.50 less 10 per cent. discount) of “Cuprase-Doctor Gaube du Gers” was purchased recently from the Anglo-French Drug Co., Ltd. It contained eight ampules each containing approximately 6 c.c. of a brownish fluorescent liquid. No information of composition was given on the box, except the line: “Chaque ampoule contient: 0 gr. .00121 de Cuivre pur” (Each ampule contains 0.00121 gr. of pure copper). The A. M. A. Chemical Laboratory reports that the preparation does contain a small amount of copper, with some protein material and about 1 per cent. sodium chlorid.

The therapeutic claims in the advertising circular are those commonly made for cancer “cures” and are about equally convincing. The publication of such statements and quotations as the following, which appear in a pamphlet “The Medical Treatment in Cancer,” cannot be too strongly condemned in a medicament that at best has only an experimental status:

“A special preparation, Cuprase, has been introduced into therapeutics which has been remarkably successful. In the history of the therapeutics of cancer, nothing has been found which can compare with the effects produced by means of Cuprase. Clinical facts carry greater weight than theoretical deductions. It follows, from the clinical observations which I have collected, that in the large majority of cases Cuprase effects the diminution or disappearance of the pains, an improvement in the general condition, a diminution or arrest of the neoplasms, and finally in certain cases, a cure has been effected. It should be remarked that all or nearly all the observations refer to inoperable cases in which the prognosis was unfavorable at an early date. It is needless to emphasize the practical importance of a preparation capable of yielding such results, even relative, in the worst stages of a disease which has always been regarded as absolutely resisting the action of all internal remedies.”

“To sum up, Cuprase has given positive results in about 94 per cent. of the cases in which it has been employed for a sufficiently long period, and some brilliant results in about 20 per cent. of these cases. Therefore, it may be affirmed, that among the internal remedies for cancer, Cuprase is the one which has produced the most successful results, and can, under certain circumstances, compete with surgical methods, even, so far as the rapidity of their results are concerned.”

“It is indicated:

(a) apart from all operation, and as a specific and curative remedy;

(b) before an operation, in order to give tone to the patient, mobilise the tumor, destroy its toxins;

(c) after the operation, as a tonic and anti-toxic, and in order to avoid frequent relapses which are always possible.”

Essentially the same statements are made in the more recent advertisements (f. i. Urological and Cutaneous Review, Feb., 1919). Opposed to these loose statements are the results of Richard Weil (The Journal A. M. A., 1913, Sept. 27, p. 1034; ibid, 1915, April 17, p. 1283). Weil avoided pitfalls of subjective impressions and used as the essential criterion of efficiency “the demonstrable reduction in size of a tumor, of a kind not to be attributed to the natural processes of evolution of that tumor or of its associated lesions” (l. c. 1915, p. 1289).

The available evidence for Cuprase is far from meeting this criterion. That published by the manufacturers and agents presents only vague generalities, and no definite data. The evidence gathered by Weil himself permits an estimate of the value of Cuprase and it is entirely unfavorable. He states (l.c. 1915, p. 1288):

“Colloidal copper has been used in recent time for the same purpose by Gaube du Gers and by others. I have recently examined the effects of colloidal copper on malignant tumors in man, and have been unable to find that it has any therapeutic value. Furthermore, a study of the distribution of the copper in tumors obtained at operation or by necropsy from individuals so treated failed to show that the copper had been deposited therein.”

In view of the extravagant and cruelly misleading therapeutic claims, and the indefinite statements of composition, the Council voted Cuprase ineligible to N. N. R., and authorized the publication of this report.—(From The Journal A. M. A., April 12, 1919.)

COLLOSOL PREPARATIONS

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below declaring “Collosol Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin” and “Collosol Sulphur” inadmissible to New and Non­official Remedies, because their composition is uncertain (conflict with Rule 1). In the few cases in which the therapeutic claims for these preparations were examined, the claims were found to be so improbable or exaggerated (conflict with Rules 6 and 10) as to have necessitated the rejection of these products.

W. A. Puckner, Secretary

The Anglo-French Drug Co., Ltd., London and New York, in November, 1918, requested the Council to consider the products “Collosol Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin” and “Collosol Sulphur.” The term “Collosol” appears to be a group designation for what are claimed to be permanent colloidal solutions, marketed by the Anglo-French Drug Co., Ltd. Were this claim correct, “Collosols” should contain their active constituents in the form of microscopic or ultramicroscopic suspensions, protected against spontaneous precipitation by the presence of proteins or some similar “stabilizers.”

According to the original patent specifications for Collosols, the metals are precipitated or treated with “peptone,” which acts as the suspending or stabilizing agent. The method of using the peptone makes it doubtful, in the first place, whether the major part of the metals is present in colloidal form, or merely in the form of peptonates, i. e., as ordinary salts. Moreover, the later patents indicate that the products have been unsatisfactory; “experience having shown that some metal colloids under certain conditions not yet fully understood have the tendency to break down after a certain period” (U. S. patent No. 1,116,247). Phenol, it is claimed has a tendency to counteract this decomposition, and the patent covers the use of phenol for this purpose.

It is difficult to see how phenol could possibly have such action. In fact, it obviously does not, for a number of the samples of Collosols submitted to the Council had separated. For instance, “Collosol Hydrargyrum” was not a colloidal solution at all, but a suspension of a coarse powder. The ampules of “Collosol Ferrum” contained a considerable quantity of flocculent precipitate. If either of these preparations were injected intravenously as directed, death might result, making the physician morally if not legally liable.

The recklessness of the claims is further illustrated by the advice that these indefinite mixtures of poisonous metals can be injected in unlimited quantities. Thus, Henry Crookes stated (Chemical News, May 7, 1914, p. 218) that Collosols “contain so small a proportion of metal, viz., 1 in 2000, that even a poisonous body like arsenic can be used with impunity.” He stated that they may be applied as a lotion, intramuscular or intravenous injection, and that “one pint or more can be injected intravenously.”

In the case of “Collosol Cocain,” as was brought out in the Council’s report published in The Journal, April 12, 1919, the manufacturers have admitted that the product is not what they have claimed—and still claim—for it. The report of the A. M. A. Chemical Laboratory showed that “Collosol Cocain,” instead of containing 1 per cent. cocain as claimed, contained, in fact, at most not more than 0.4 per cent. cocain.

The report of the A. M. A. Chemical Laboratory on the Collosol products was sent by the Council to the New York office of the Anglo-French Drug Co., Ltd., in duplicate in order to facilitate reference to the London office. This was some months ago. The information which the Council requested has not yet been received, nor has the Anglo-French Drug Co., Ltd., indicated its intention of supplying such information. On the other hand, claims to which specific objection have been made, continue to appear in current advertising. Accordingly, the Council authorizes publication of this report, and declares the Collosol preparations previously named ineligible to New and Non­official Remedies.

Additional Notes on Collosol Evidence

In addition to the preceding the following notes of the referee on the evidence so far submitted were sent to the Anglo-French Drug Company, Ltd., for consideration:

Collosol Iodine: The leaflet which describes Collosol Iodine contains claims that are improbable, not in accord with accepted facts nor substantiated by evidence; for instance:

“This preparation contains Iodine in its most active form ...”

“The disadvantages of ‘iodism’ and nausea frequently associated with iodides never occur with Collosol Iodine.”

“In the case of Colloidal Iodine the whole of the Iodine is absorbed and enters into molecular combination with protein to form an iodo-amino acid and ... exerts a reducing action on the lipoids producing a different condition of the blood—hence the use of Iodine as an ‘alterative’.”

“Intravenously the action of Collosol Iodine is more rapid ... in cases of pyemia ... thus showing its absolute non-toxicity.”

“ ‘Per se’ Colloidal Iodine is only slightly parasitotropic and bacteriotropic but micro-organisms are very greatly influenced by its action, and not only is the effect of a subsequently administered remedy greatly increased but also the insoluble colloidal protein of serum itself is reduced to smaller particles, thus increasing its surface and adsorptive capacity and consequent germicidal power. In some cases the serum, thus aided, is enabled to throw off a milk microbial invasion. The above action can be readily demonstrated ‘in vitro’ by means of the ultramicroscope.”

“In Cancer, the intravenous injection of Collosol Iodine relieves pain, even where large dosage of morphine is ineffective.”

“In Rheumatism the ionic method of treatment with Collosol Iodine is strongly advised.”

“In Recovery from Alcoholism the internal administration of Collosol Iodine restores the normal condition of cell activity, ensuring rapid recovery.”

Collosol Hydrargyrum: This is said to be a preparation of colloidal mercury and would therefore be similar to Electromercurol (New and Non­official Remedies, 1919, p. 167). Colloidal mercury preparations have been used to some extent; they appear to have no decided advantage over other, noncolloidal, mercury compounds. They differ sufficiently from them, however, to justify acceptance for New and Non­official Remedies, providing that reasonable claims are made for them. The leaflet advertising Collosol Hydrargyrum contains statements that cannot be accepted and require thorough revision to make them acceptable. The following are instances:

“Although—especially locally—the action of mercurials is markedly antiseptic, when taken internally or injected, it has been stated by some of the best known authorities, that their action is rather to increase the natural resisting power of the body to disease, probably because of stimulation of the oxidases.”

With the soluble mercurials “considerable upset of the normal cell conditions of the tissues ensues whilst these soluble salts are being converted to a condition in which the body can make use of them.”

“The colloidal state ... is stated by some authorities in the case of mercury to be invariably precedent to absorption.... With the usual forms of mercury the danger of too great a dose per cell is considerable, but in the case of colloidal mercury, the diffusion is extremely rapid and chemical affinity low. Hence the danger to the individual leucocyte is minimized and the maximum effect obtained.”

“... absence of pain is usual in the administration of colloidal preparations and is due to their isomorphism with the colloidal lipoid and protein of the tissues and body fluids.”

“According to McDonagh,... mercury acts as an oxidizing agent and that the process of oxidation is more effective in the early stages of syphilis in producing the death of the causal organism ...”

Collosol Manganese: The circular submitted to the referee is a reprint of a paper by Sir Malcolm Morris on “The Treatment of Furunculosis and Other Deep-Seated Coccogenic Infections by Collosol Manganese.” It reports four cases of furunculosis, each of which cleared up after the intramuscular injection of a few doses of Collosol Manganese. The author seems to attribute the cure to the manganese but the evidence is not convincing. Even the author admits that, in the treatment of furunculosis in general “when at last the dismal procession ends, this often appears to be less the result of treatment than because the disease has run its natural course.” Unless much better evidence is in existence, the preparation must be considered to conflict with Rule 6, which requires therapeutic claims to be substantiated.

Collosol Argentum: The evidence submitted as to actions consists of a single reprint by Roe, which is not convincing, and this fantastic statement by Boys:

“A young girl, aged 18, came to my house with acute inflammation of one eye with an ulcer on the cornea. Two drops of Collosol Argentum were dropped in the eye at 7 p. m., and a pad placed over the eye. When she came next morning the eye was quite well; the ulcer had disappeared, and there was no inflammation.”

There is no evidence that this preparation acts as catalyzer and assists the natural resisting bodies of the tissues; or that these are “oxygen carriers.” Unless the claims are supported by better evidence, they, in the opinion of the referee, could not be accepted.

There have been submitted to the Council samples of the following metallic Collosols:

Collosol ArgentumCollosol Ferrum

Collosol ArsenicumCollosol Hydrargyrum

Collosol CuprumCollosol Manganese

Also Collosols of Iodine and Sulphur, and finally Collosols of Cocain and Quinin. Of all the above, except sulphur, only three small ampules have been submitted. This does not admit of any chemical examination but a statement of the physical appearance may be of interest.

Collosol Arsenicum, 0.2 per cent.: Very turbid with large quantities of a lemon yellow flocculent precipitate. On shaking does not become homogeneous and rapidly separates again.

Collosol Argentum, 1-2000: The liquid has a slight opalescence. There is considerable deposit of a heavy black precipitate. Does not become homogeneous on shaking and the black substance quickly separates again.

Collosol Cuprum, 0.5 per cent.: Dark red somewhat opalescent liquid. No precipitate. May be colloidal.

Collosol Ferrum, 1-2000: Liquid clear. Large quantities of dark brown flocculent precipitate. The precipitate is not distributed evenly when the mixture is shaken and settles out quickly on standing.

Collosol Hydrargyrum, 5 per cent.: Milky liquid. Large quantities of white deposit mixed with considerable black. The deposit mixes fairly well but the greater part settles out after standing an hour or two.

Collosol Manganese, 2.5-1000: Clear reddish-brown liquid without deposit of any kind. Is not opalescent or fluorescent.

Collosol Iodin, 1-500: Very pale straw colored liquid without deposit. Has a slight opalescence.

Collosol Sulphur, 1-100: Liquid is opalescent. There is some deposit of yellow particles. A four ounce bottle was also submitted. The liquid in this bottle is milky with considerable deposit of yellow crystals like ordinary crystalline sulphur.

Collosol Cocain, 1-100: Transparent, colorless liquid with no deposit. Chemical examination showed 0.4 per cent. of what may have been cocain. This residue gave alkaloidal tests.

Collosol Quinin, 1-100: Slightly opalescent, colorless liquid, with no deposit. Gives alkaloidal reactions.—(From The Journal A. M. A., June 7, 1919.)

PULVOIDS CALCYLATES COMPOUND

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report, not so much because the preparation with which it deals is of any great importance, but as a protest against the large number of similar irrational complex mixtures which are still offered to physicians.

W. A. Puckner, Secretary.

Pulvoids Calcylates Compound (The Drug Products Co., Inc.) are tablets each of which is claimed to contain:

“Calcium and Strontium Disalicylate, 5 grs.; Resin Guaiac, ¹⁄₂ gr.; Digitalis, ¹⁄₄ gr.; Cochium [colchicum?] Seed, ¹⁄₄ gr.; Squill, ¹⁄₄ gr.; Cascarin, ¹⁄₁₆ gr. with aromatics.”

“Pulvoids Calcylates Compound (Sugar coated orange color)” is advertised (Medical Times, January, 1919) as being “Analgesic-Antipyretic and Diuretic,” and is included in the preparations designated by the advertiser as “Approved Remedies for LaGrippe and ‘Flu.’ ” The claim that “Their tolerance is remarkable” refers not to the physicians who tolerate such products, but to the alleged fact that Pulvoids Calcylates are tolerated remarkably well. The advertisement continues:

“May be given persistently and continuously without gastric disturbances.”

“They are uniformly efficient. More certain in effect than the ordinary Salicylates.”

It would be difficult to find an advertisement of equal length containing a greater number of misleading or directly false statements than are found in this one. The Journal (April 22, 1916, p. 1307) has called attention to the lack of justification for this absurd mixture of drugs and has discussed the preparation with especial reference to its use in acute rheumatism, in which the salicylates occupy a special field. The advertisement just quoted mentions La Grippe and “Flu” (or Influenza) as special fields of usefulness for this preparation. This, apparently, is merely an attempt to spread the sail for any breeze. Salicylates have a field of usefulness in influenza in that they often afford relief from pain. There is no reason to suppose that a mixture containing calcium and strontium salicylates—the “Calcium and Strontium Disalicylate” of Pulvoids Calcylates is probably a mixture of calcium and strontium salicylate127—has any greater salicylic effect than an equal amount of sodium salicylate. On the other hand, it is worse than useless to give colchicum, squill and digitalis for the relief of such pains.

Should cardiac dilatation develop, and digitalis medication be required it would be impossible to adjust the dose of such a mixture with special reference to the digitalis action, which alone would be indicated for that condition. No educated physician at present would think of giving resin of guaiac merely because his patient required digitalis, nor would he administer “cascarin,” whatever that may be, in fixed doses, every time he gave a dose of salicylate.

It is impossible to recognize the several effects induced by this therapeutic omneity, and the medical profession should consider it an insult to be offered mixtures such as Pulvoids Calcylates Compound.

Pulvoids Calcylates Compound is, per se, of no great importance; it is one of a type. It has been selected as one of the utterly irrational and therefore potentially dangerous mixtures, that may be found by the score or the hundred in the catalogues of practically every pharmaceutical manufacturing firm in the United States.—(From The Journal A. M. A., June 14, 1919.)

PROTEOGENS OF THE WM. S. MERRELL COMPANY

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the statement which appears below, declaring Proteogen No. 1 (Plantex) for Cancer, Proteogen No. 2 for Rheumatism, Proteogen No. 3 for Tuberculosis, Proteogen No. 4 for Hay Fever and Bronchial Asthma, Proteogen No. 5 for Dermatoses, Proteogen No. 6 for Chlorosis, Proteogen No. 7 for Secondary Anemia, Proteogen No. 8 for Pernicious Anemia, Proteogen No. 9 for Goitre, Proteogen No. 10 for Syphilis, Proteogen No. 11 for Gonorrhea, and Proteogen No. 12 for Influenza and Pneumonia inadmissible to New and Non­official Remedies because their composition is secret; because the therapeutic claims made for them are unwarranted; and because the secrecy and complexity of their composition makes the use of these preparations irrational.

The Council took up the consideration of the Merrell Proteogens because of inquiries received, and on January 27 invited the Merrell Company to aid in the proposed investigation by submitting information in regard to the composition of the preparations, submitting the current advertising, and presenting evidence for the claims that were made for the preparations. While the Merrell Company agreed to submit the requested information, this had not been received at the time the report of the referee to whom the products had been assigned (Referee 1), was adopted. This report was sent to the company on April 4. In reply the Merrell Company protested against the conclusions of the report and submitted considerable material in an attempt to support the claims made for the products. This material was examined by the first referee and then transmitted to a second referee (Referee 2) for consideration. The second referee concluded that the matter submitted offered no evidence that would justify the Council in modifying the report first adopted, and hence recommended that its publication be authorized.

In accordance with this recommendation (report of Referee 2) the Council authorized the publication of the reports of both the first and second referees.

W. A. Puckner, Secretary.

Report of First Referee on Proteogens

“Proteogens,” according to the William S. Merrell Co., are “Polyvalent Proteins of Non-Toxic Plant Origin.” The subject of Proteogens can best be approached by recalling the history of “Autolysin,” an alleged remedy for cancer, originated by A. S. Horowitz, Ph.D. This was exploited some years ago, and was finally shown to be worthless. Proteogens are said to be prepared “under the personal supervision of the originator, Dr. A. S. Horowitz.” The composition of the different Proteogens is essentially secret. The assertion was made at one time, but is not found in the present advertising matter, that Plantex—now called “Proteogen No. 1”—is similar to Autolysin. Now the Proteogens are said to be “prepared by a special process employing various combinations of plants.” Further:

The biologic principles present are chlorophyll, chromoplast, lipoids and vitamines; these are ferments or enzymes. The vegetable acids, metalloids and metals present in all plants in colloid form act biochemically. Among the metalloids are hydrogen, carbon, manganese, oxygen, sulphur, phosphorus and chlorine; the heavy metals are iron, potassium, sodium, magnesium and copper. These biochemic principles are always present in plants as colloids.”

It is claimed by the Merrell Company that:

“Proteogens stimulate the cytogenic mechanism to higher activity; therefore, indirectly cleave the invading microorganism and eliminate their special toxins. Proteogens swing the disturbed metabolism back to normal and, by natural processes, build up effective defenses against recurrent bacterial attacks.”

Proteogen No. 1 was first introduced as “Plantex,” and at that time the Merrell Company referred to a preparation that was the result of “a series of studies” carried out by a “noted biologist” with a view of “evolving a Cancer remedy” that was “to be autolytic in character,” and announced:

“The House of Merrell always interested in the progress of plant therapy, began pharmacological experimentations to reproduce this same substance. The qualitative and quantitative analysis of the substance as used in New York having been published simplified matters. A somewhat similar remedy has now been prepared. It consists of the following substances—Menyanthes trifoliata [Buckbean], Melilotus officinalis [Yellow sweet clover], Mentha crispa [Curled mint], Brassica alba [White mustard], Anemone hepatica [Liver leaf], Viola tricolor [Pansy], Anthemis [Roman chamomile], Fructus colocynthidis [Colocynth], Lignum quassiæ [Quassia], Urtica dioica [Nettle], Radix rhei [Rhubarb root], Hedge hyssop. These substances are in approximately equal proportions with the exception of the mustard which forms 20 per cent. of the mixture, and the colocynth fruit which is 5 per cent.”

With respect also to the other Proteogens listed above, study of medical literature revealed no evidence establishing their therapeutic value; in fact, no evidence was found other than that appearing in the advertising matter of the manufacturer. The range of diseases in which Proteogens are recommended is so wide as to make obvious the lack of scientific judgment which characterizes their exploitation. A circular letter, received January, 1919, reminded the physician that about a year ago his attention had been directed to Proteogen No. 1 for cancer, that later developments enabled the firm to recommend for his consideration “a series of Proteogens (Nos. 2 to 9),” and that now “In response to an insistent demand, Dr. A. S. Horowitz has prepared two new Proteogens—No. 10 for Syphilis and No. 11 for Gonorrhea.” A postscript to this circular letter announced another preparation, “Proteogen No. 12 for Influenza and Pneumonia,” a “development out of the present influenza epidemic,” and admitted that “It has not had the clinical experimentation that precedes our introduction of a new product.”

The introduction of No. 12 was effected by means of a special bulletin which consists exclusively of clinical reports from seven physicians, all from Chicago save one, and all purporting to show most favorable results from No. 12. They describe cases which any physician with experience with influenza can duplicate without any special treatment.

It is difficult to give serious consideration to a set of alleged remedies when the only evidence is that furnished by the proponents of the alleged remedies. This is particularly true when the alleged remedy does not make a sufficient appeal to one’s sense of the rational in therapeutics to lead one to feel justified in asking a trial at the hands of careful clinical observers. Considering the grave nature of the diseases for which Proteogens are recommended, particularly cancer, tuberculosis, and pernicious anemia, the want of a rational basis for the method of treatment and the general tenor of the advertising matter, it appears safe to conclude that these agents do not represent any definite advance in therapeutics.

As the use of preparations, secret in composition, and of no established value, is contrary to rational therapy, it is recommended that the Proteogen preparations be declared in conflict with Rules 1, 6 and 10.

Report of Second Referee Reviewing Manufacturers’ Reply

The report declaring the Proteogens of the William S. Merrell Company inadmissible to New and Non­official Remedies was adopted by the Council, but before publication it was sent to the Merrell Company for such comments as it might desire to make. In due time the reply of the firm was received. It consisted of two volumes bound in limp morocco, each stamped in gold: “Report Proteogen Therapy Requested by the American Medical Association, 1919; The Wm. S. Merrell Company.” The first volume contained 79 pages of typewritten material; the second volume contained 76 pages of typewritten material and a number of advertising booklets put out by the Wm. S. Merrell Company, exploiting the Proteogens.

Among the typewritten material was a 14-page report on “Proteogen Therapy” by its originator, A. S. Horowitz. Following this there are several pages devoted to what is termed “a short qualitative description of the ingredients of major importance in Proteogens.” Then follows a page describing the advertising of Proteogens, and the remainder of the two books is devoted to testimonials, lauding the benefit of Proteogens in diseases such as cancer, tuberculosis, rheumatism, asthma, influenza, enlarged prostate, rheumatic endocarditis, syphilis, eczema, psoriasis, diabetes, secondary anemia, gono­coccic infections, etc. Finally, there are attached samples of advertising pamphlets.

The dissertation by A. S. Horowitz contains little actual information concerning these substances, but is concerned principally with discussion of foreign proteins, “antiferments,” “non-specific proteins,” “anti-virolins” and speculations on their hypothetical actions and interactions on each other and on the organs of the body and on bacteria. The report contains many questionable statements.

One finds in this report but few definite statements of facts which are known to be accurate or which could be accepted without question. The qualitative description of the proteins and their components is as vague as the previous discussion. The differentiation between the various Proteogens is extremely indefinite; that for Tuberculosis, No. 3 is described as “polyvalent, non-specific protein which rapidly attacks the acid-fast, encapsulated tubercle bacilli”; Proteogen No. 10 for syphilis is said to be a combination of “non-specific plant proteins and different chemicals which has the power to paralyze and destroy living spirochete.” It is stated that Proteogens are scientific preparations based on standard ingredients and that the standard­ization is more accurate than in serums, vaccines or toxins, etc. The report gives no proof of such statements.

The testimonials that are submitted are typical of “reports” that manufacturers are able to obtain from some physicians, to prove the efficacy of almost any preparation in any disease. Each consists, practically, of the opinion of the individual who has employed the Proteogens or the opinion of the patient who has been treated. Few data are given in these reports from which an impartial conclusion might be drawn. A few of the testimonials presented by the William S. Merrell Company follow. The valuelessness of such material as scientific evidence is obvious:

Rheumatism:—Proteogen No. 2.—The Doctor has one case being treated with No. 2. She has improved so rapidly she cannot express her pleasure, and will continue for some time on the treatments. She is a patient who was confined during the time she suffered from a rheumatic illness, and it seemed to affect her mental condition. This condition is clearing up also, very much to the pleasure of both patient and doctor.—November 27, 1918.

Influenza:—Proteogen No. 12.—First day, temperature 102, gave 1 c.c. Proteogen No. 12; second day, temperature 100, gave 1 c.c. Proteogen No. 12; third day, temperature 98.8, gave 1 c.c. Proteogen No. 12, and then discharged the case as recovered.—October 31, 1918.

Asthma:—Proteogen No. 4.—Splendid results obtained from a sample of Proteogen No. 4. Three ampoules affected [effected?] complete recovery.—October 9, 1918.

Cancer:—Proteogen No. 1.—Mrs. B. pronounced recovered from Cancer by Dr. O. W. A., of Catlin, after having injections of Proteogen No. 1 for some time.—October 4, 1918.

Eczema:—Proteogen No. 5.—Tried No. 5 on a patient with eczema, and with happy results. Have not done anything for him for about five months—and he is now at his business. Proteogen No. 5 also RELIEVED HIM OF CONSTIPATION AND WHAT HE CLAIMED A TRAUMATIC STRICTURE OF THE LOWER PORTION OF SIGMOID FLEXURE. He is sure pleased and recommending them to his friends. (Proteogens).—February 17, 1919.

Syphilis:—Proteogen No. 10.—I am getting such excellent results with the No. 10 Proteogen for Syphilis that I am badly in need of more, as I am treating so many cases. Please send me four dozen C. O. D.—October 9, 1918.

Enlarged Prostate:—Proteogen No. 1.—Have used Plantex in four cases, with good results in each case. One of them his father, an elderly man.—April 25, 1918.

Lobar Pneumonia:—Proteogen No. 12.—The only case I have used Proteogen No. 12, was a man who had Lobar Pneumonia of left lung following Influenza. After crisis came, patient continued to have slight rise in temperature, cough, and after using 10 doses of your Proteogen No. 12, temperature was normal, cough very much better, patient began to take on flesh and is still improving.—December 26, 1918.

Tuberculosis:—Proteogen No. 3.—The Doctor writes: The Proteogen No. 3 sent me worked wonders in my patient. The case came under my care when he was too far gone for anything to benefit him a great deal, but the Proteogen did for him more than anyone could have expected, yet he died leaving me with a few ampoules to try on the next patient.—September 20, 1918.

Gonorrheal Cystitis:—Proteogen No. 11.—My patient has taken two boxes of your Proteogen No. 11 given for gonorrheal cystitis of probably two years’ standing and at this writing I consider her almost, if not entirely, cured which I think speaks very highly of your remedy. I expect to use more of your preparations in the future.—April 12, 1919. [This testimonial, either by clerical error, or because the results were considered remarkable, was repeated elsewhere in the material submitted by the Merrell Company.]

Acute Gonorrhea:—Proteogen No. 11.—Mr. A. E. R., age 65, weight 140 pounds. First attack. Had had no previous treatment. Came to me January 2, 1919. Had discharge, all acute symptoms, burning, etc. Gave seventeen injections of Proteogen No. 11, also mild antiseptic urethral wash. Discharged on February 15, 1919, clinically cured.—April 11, 1919.

Epithelioma of Buttock.—Proteogen No. 1.—I used Proteogen No. 1 on an epithelioma of buttock some six months ago with favorable results and no return of symptoms as yet.—April 13, 1919.

It is obvious that the Proteogen preparations are in conflict with Rules 1, 6 and 10, and should not be admitted to “New and Non­official Remedies.” It is recommended that the previous action of the Council be allowed to stand and that publication of both reports be authorized.—(From The Journal A. M. A., July 12, 1919)

“ARSENOVEN S. S.” AND “ARSENO-METH-HYD”

Report of the Council on Pharmacy and Chemistry

The Council authorizes publication of the following report. This report declares Arsenoven S. S. of the S. S. Products Company and Solution of Arsenic and Mercury (formerly called Arseno-Meth-Hyd) of the New York Intravenous Laboratory, inadmissible to New and Non­official Remedies. The Council takes this opportunity to repeat its warning against the abuses—often dangerous—to which patients are frequently subjected when “intravenous therapy” is employed.

W. A. Puckner, Secretary.

Because of inquiries received, the Council took up the consideration of Arsenoven S. S. and Arseno-Meth-Hyd (now sold as Solution of Arsenic and Mercury). The preparations having been referred to a committee for consideration, this committee reported:

ARSENOVEN S. S.

“Arsenoven S. S.” is a preparation put out by the S. S. Products Company, Philadelphia. The claims are made that it is “a simplified office treatment for syphilis” and is “a combination of arsenic and mercury for office use, offering maximum efficiency, safety and convenience.” According to the company, “Arsenoven S. S.” contains Dimethylarsenin 15.4 grains, Mercury biniodid ¹⁄₁₀ grain, Sodium iodid ¹⁄₂ grain. With regard to the identity of “dimethylarsenin” the company claims: “This product is a compound of cacodylic acid similar to sodium cacodylate but with a more pronounced therapeutic action.” The committee recommends to the Council that “Arsenoven S. S.” be declared inadmissible to New and Non­official Remedies because of unwarranted therapeutic claims.

ARSENO-METH-HYD

“Arseno-Meth-Hyd,” is sold by the New York Intravenous Laboratory, New York City, for the treatment of syphilis. It comes in three dosages, 2 gm., 1.5 gm., and 0.7 gm., respectively. The claim is made that “Arseno-Meth-Hyd 2 gm.” contains “2 gm. (31 grains) of Sodium Dimethylarsenate (Cacodylate), U. S. P.. and Mercury Iodid 5 mg. (¹⁄₁₂ grain)” in 5 c.c. of solution. Physicians are told:

“In primary and early secondary case administer Arseno-Meth-Hyd 2 gm. every sixth day and Mercury Oxycyanide .008 (¹⁄₈ grain) intravenously between each injection.”

“In Tertiary cases and those of long standing alternate with intravenous injection of Sodium Iodid 2 gm.”

The following claims are made for the alleged effectiveness and safety of the cacodylate:

“This methyl compound of arsenic has come into almost universal use for syphilis. On account of lack of toxicity an aggressive routine can be carried on. The simple technic and absence of reactions make it most desirable for the regular practitioner. This large dose gives more uniform results both as healing manifestations and negative Wassermann’s.”

“Much discussion has surrounded the use of Methyl Compounds of Arsenic and it has been demonstrated beyond doubt that Cacodylate of Soda proves an effective remedy for syphilis provided that it is properly administered.” [sic]

“The low toxicity of this Methyl compound of arsenic is remarkable. It is contraindicated only where a decided idiosyncrasy for even small doses of arsenic exists.”

These statements are essentially false and misleading. Cacodylate has not come into universal use in the treatment of syphilis, nor has its usefulness been “demonstrated beyond doubt.” On the contrary, H. N. Cole (The Journal, Dec. 30, 1916, p. 2012) has shown that doses so large as to produce renal injury were almost totally ineffective against syphilis. Obviously, “effective doses” if such exist, are not harmless. The dosage advised for Arseno-Meth-Hyd may not produce acute toxic symptoms; nevertheless smaller doses have produced nephritic phenomena. The “Arseno-Meth-Hyd” treatment includes the intravenous injection of about ¹⁄₄ grain of a mercury salt. Although this is less than the usual dose (about 1 grain per week), the mercury is probably more effective than the cacodylate.

The committee recommends to the Council that, because of the unwarranted therapeutic claims, “Arseno-Meth-Hyd” be held inadmissible to New and Non­official Remedies.

The Council adopted both reports of the committee and declared “Arsenoven S. S.” and “Solution of Arsenic and Mercury” (“Arseno-Meth-Hyd”) inadmissible to New and Non­official Remedies. The committee’s reports on these two products impel the Council again to call attention to the undesirable and dangerous abuses to which “Intravenous Therapy” lends itself. There is a distinct field for the intravenous administration of drugs in those cases in which immediate drug action is necessary, or when the medicament is likely to be changed if absorbed through the ordinary channels. Unless such indications exist, however, intravenous administration involves not only inconvenience and expense to the patient, but what is more important, unnecessary danger. The fact that indiscriminate intravenous administration is peculiarly profitable to certain manufacturing houses makes it all the more necessary for the medical profession to be on its guard in this matter.

In this connection it is well worth while to quote the closing paragraph from an editorial on “Intravenous Therapy” that appeared in The Journal, Nov. 11, 1916. It is as true today as when it appeared:

“Intravenous therapy will be most securely advanced if its employment is restricted to such well defined fields. [As those mentioned above.] These fields can be satisfactorily determined only by a scientific pharmacologic study of the action of these drugs when so administered in animals, as well as in man, under conditions in which the results are carefully controlled. The intravenous method is an impressive one, approaching in preparation almost to that which goes with a surgical operation. The patient is usually interested and impressed by this new, and, to him, mysterious method. There is a psychic element in his reaction to the injection which is not a factor in his reaction to the same drug when given by mouth. The intravenous injection of a complex mixture would appear to be particularly reprehensible. Little is known, as has been stated, of the results to be expected from intravenous therapy, even with simple substances. The use of complex mixtures will without doubt react against the proper use of the method.”

After the report on Arseno-Meth-Hyd had been presented to the Council, a letter was received from the New York Intravenous Laboratory announcing that the preparation “Arseno-Meth-Hyd” was now called “Solution of Arsenic and Mercury” and expressing a desire to have its products accepted for inclusion in New and Non­official Remedies. In view of this letter, the committee’s report on “Arseno-Meth-Hyd” and the Council’s protest against promiscuous intravenous therapy were sent the New York Intravenous Laboratory for consideration.

The reply of the New York Intravenous Laboratory contained nothing which permitted a revision of the preceding report. The change of the name of “Arseno-Meth-Hyd” to “Solution of Arsenic and Mercury” means little as the name still does not disclose the important fact that the arsenic is present as sodium cacodylate, nor does it tell the character of the mercury compound. The Council voted that “Solution of Arsenic and Mercury” and “Arsenoven S. S.” be declared inadmissible to New and Non­official Remedies because the therapeutic claims advanced for them are unwarranted (Rule 6) and because the names of these pharmaceutical preparations are not descriptive of their composition (Rule 8).

In filing its reply with the Council, the New York Intravenous Laboratory announced that that document would be circulated to the medical profession. This is of course the firm’s privilege. The Council notes, however, with interest, that the reply is devoted almost entirely to points which were not raised by the Council and that it fails to discuss the objections which were actually made.

The reply constantly confuses the efficiency of cacodylate in anemia and in syphilis. The Council’s report on “Arseno-Meth-Hyd” does not discuss or even touch on the question of cacodylates in anemia. It is confined to a discussion of the disappointing results obtained with cacodylates as such (i. e., without mercury) in the treatment of syphilis. This attempt on the part of the New York Intravenous Laboratory to confuse the issue and to attribute to the Council an opinion that it has never stated or held is an inexcusable misrepresentation. The company in its reply said:

“We believe that you have previously stated that a solution cacodylate of soda possesses no more action than so much water. In other words, it was inert. Now you try to show that it produces renal injury.”

The Council has never declared that cacodylates are inert. In the report it is merely stated “that doses so large as to produce renal injury were almost totally ineffective against syphilis.” Neither has the Council stated that cacodylate is “peculiarly dangerous.” In fact the absolute toxicity of cacodylates is low but Cole’s results were quoted as a caution that “effective” doses are not harmless. A great portion of the remainder of the reply is devoted to disparaging arsphenamin—a product that is not involved in this action of the Council, and one about which the physician is amply informed.

Amongst other wholly extraneous matters, the firm’s “reply” tried to resurrect the pepsin pancreatin controversy. This also has nothing to do with the efficiency or harmlessness of sodium cacodylate. In order to dispose of the matter, however, it may be pointed out that the implications are entirely misleading. The work which is quoted against the Council was undertaken by the Council itself, to clarify obscurities in the older data. The outcome of these new investigations showed the essential correctness of the deductions from the older work, namely, that pancreatin is destroyed by pepsin-hydrochloric acid. Dr. Long’s work to which the firm’s reply evidently refers, showed that under favorable conditions, namely, when protected by an excess of protein, some trypsin may escape destruction in the stomach; but it fully confirmed the original conclusion that pepsin and pancreatin mixtures as ordinarily administered are practically worthless (J. H. Long, Jour. Amer. Pharmaco. Assoc., Sept. 19, 1917).

As regards the editorial on intravenous therapy, a concession may be made the New York Intravenous Laboratory: intravenous injections are no longer quite as “impressive” as in 1916, but that does not alter the fact that they should be used only when a distinct advantage is to be gained.—(From The Journal A. M. A., Aug. 2, 1919)

HORMOTONE AND HORMOTONE WITHOUT POST-PITUITARY

Report of the Council on Pharmacy and Chemistry.

“Hormotone,” of the G. W. Carnrick Company, is advertised as “A pluriglandular tonic for asthenic conditions.” “Hormotone Without Post-Pituitary” is recommended for use “in neurasthenic conditions associated with high blood pressure.” These preparations are sold in the form of tablets for oral administration. The Council declares these preparations inadmissible to New and Non­official Remedies because: (1) Their composition is semisecret (Rule 1); (2) the therapeutic claims are unwarranted (Rule 6); (3) they are sold under names not descriptive of their composition but suggestive of indiscriminate use as “tonics” (Rule 8); (4) in the light of our present knowledge the routine administration of polyglandular mixtures is irrational (Rule 10). In explanation of this action, the Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Each tablet of “Hormotone” (G. W. Carnrick Co., New York City) is said to contain ¹⁄₁₀ grain of desiccated thyroid and ¹⁄₂₀ grain of entire pituitary, together with the hormones of the ovary and testes—the amounts and the form in which the latter are supposed to be present are not given. From this it will be seen that the only definite information given to the medical profession regarding the composition of Hormotone is that it is a weak thyroid and a still weaker pituitary preparation.

What results can be anticipated from one or two tablets three times daily (the recommended dose of Hormotone) each containing ¹⁄₁₀ grain of thyroid and ¹⁄₂₀ grain entire pituitary? Such doses of thyroid may, of course, have a beneficial action in a limited number of cases of myxedema and cretinism. An extract of the posterior lobe of the pituitary (Liquor Hypophysis, U. S. P., for example) will, when injected subcutaneously or intramuscularly, have a pronounced effect on the parturient uterus; its action on certain other forms of smooth muscle will be much less certain. But the oral administration (for which Hormotone is recommended) of the posterior lobe of the pituitary has not been shown to have any such effect. The use of the anterior lobe in doses of 1 to 4 grains (doses very many times larger than those recommended for the entire gland in Hormotone) is in the experimental stage and its only probable value seems to be in those cases of known gland deficiency.

As to the other alleged ingredients of Hormotone—hormones of the ovary and testes, amounts not stated: all physicians know the uncertainties attending the use of ovarian preparations and the serious question as to whether testicular extracts have any therapeutic value. Whatever may be the physicians views as to the probable therapeutic value of these organs, the first thing he desires to know is how much of the substance he is giving and from what part of the gland it is obtained.

So much for the facts; yet the physician is asked to jump from this region of solid fact into a sea of hypothesis; to believe that small amounts of the well-known drugs thyroid and pituitary, plus an unknown amount of unknown hormones of the testes and ovary are of great value in conditions that in themselves are often purely hypothetical. He is asked to believe that this combination has virtues in such conditions as “hypofunction of the adrenal system,” neurasthenia, the “fatigue syndrome,” amenorrhea, dysmenorrhea, “natural and artificial menopause,” sexual neuroses, cold extremities, cardiac asthenia, low blood pressure, infantilism, sterility, melancholic conditions, obesity, anorexia, anemia, slow metabolism, constipation, psychasthenia, lowered virility and the sexual neuroses of the unmarried, hysteria following functional exhaustion of the nerve centers, frigidity, etc., etc., especially if he guesses that the trouble is due to a “pluriglandular disturbance,” “glandular hypofunction,” an “adreno-pituitary deficiency,” suboxidation, etc.

The physician is invited to use Hormotone because, among other reasons, each alleged constituent is said to be “in physiologic sympathy and therapeutic harmony with the others,” and further, because:

“Pluriglandular therapy has the endorsement of high authorities, is both logical and effective and Hormotone is a splendid example of it. It will be seen at its best where the patient lacks snap and vim and vigor. Asthenic conditions necessarily indicate hypofunction of the adrenal system ...” etc.

“The use of gland extracts in the treatment of aplasias of the pluriglandular system has become an established therapeutic measure of miraculous potency (Bayard Holmes: The Internal Secretory Glands, Lancet-Clinic, Sept. 19, 1914).”

The G. W. Carnrick Company also advertises a “Hormotone Without Post-Pituitary,” each tablet of which is said to contain ¹⁄₁₀ grain desiccated thyroid, and to “present” “hormone bearing extracts of thyroid, anterior pituitary, ovary, and testes.” This product is just as irrational as “Hormotone.”—(From The Journal A. M. A., Aug. 16, 1919)

FORMALDEHYDE LOZENGES

Report of the Council on Pharmacy and Chemistry

The Council has voted Hex-Iodin (Daggett and Miller Co., Inc., Providence, R. I.), Formitol Tablets (E. L. Patch Co., Boston), and Cin-U-Form Lozenges (McKesson and Robbins, New York City) inadmissible to New and Non­official Remedies, and authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Some years ago, the Council published (The Journal A. M. A., Aug. 28, 1915, p. 816) a report on Formamint, a proprietary medicine widely exploited as a peculiar chemical compound of sugar of milk and formaldehyde. The formaldehyde was said to be liberated slowly by the action of the saliva, and because of this liberation of formaldehyde, Formamint was claimed to be a powerful germicide. Extravagant claims were made for its curative and prophylactic effects. The Council found that the therapeutic claims were grossly unwarranted and that its exploitation to the public was a public danger.

During the recent epidemic of influenza, a variety of tablets or lozenges were advertised, and are still being advertised, having formaldehyde, in some form or other, as the nucleus around which revolve the therapeutic claims. In some cases, the advertising clearly indicates the character of the formaldehyde compound that is claimed to be present; in others the statements are vague and indefinite or misleading.

It is hardly necessary to remind physicians that the use of tablets containing hexa­methylen­amin or other formaldehyde compounds can neither cure respiratory infections, nor even confer protection against such infections. To be effective, formaldehyde would need to be supplied to the entire respiratory tract continuously for some time or else in concentrations that would be distinctly irritant and damaging to the tissues. Saliva-dissolved tablets, obviously cannot reach the nasal or tracheal mucosae directly; and the application of quickly acting concentrations of formaldehyde is out of the question. This altogether aside from the fact that hexa­methylen­amin, the basis of some of these tablets, does not liberate formaldehyde in the mouth, and for this reason alone would be quite useless for this purpose! (See Hanzlik and Collins, Archives of Internal Medicine, November, 1913.)

An inefficient antiseptic is more than merely useless; it is a menace to public safety, in that it tends to lead to the neglect of rational and effective protective measures. It therefore seems advisable for the Council again to call the attention of physicians to the subject. Accordingly, three specimens of these products were purchased and examined in the Association’s Chemical Laboratory.

Hex-Iodin

Hex-Iodin (Hexamethylenetetramine and Iodum) Lozenges are manufactured by Daggett and Miller Company, Inc., Providence, R. I. They weigh 15¹⁄₂ grs. each, are sweetened and are flavored with mint or menthol. The package and circulars do not contain a definite statement of composition. The rather indefinite synonyms “Hexameth. and Iodine Comp.” and “Hexa­methylene­tetramine and Iodum” suggest that the lozenges contain hexa­methylen­amin and free iodin. The further statement that they “contain the combined medicinal antiseptic and prophylactic properties of Hexa­methylene­tetramine and Iodum” is also rather indefinite. The therapeutic action claimed for the lozenges, however, could only be produced by free iodin and by liberated formaldehyde.

It is unnecessary to discuss in detail the extravagant claims made for these lozenges. The inefficiency of hexa­methylen­amin has already been referred to; the limitations of iodin, free or combined, in lozenge form, need not be discussed because the examination made in the A. M. A. Chemical Laboratory showed that Hex-Iodin lozenges contained no free iodin, and only traces of combined iodin. Neither formaldehyde nor para­form­aldehyde was present; hexa­methylen­amin was present but, the lozenges being neutral no formaldehyde is generated in contact with water or with the alkaline saliva.

Thus Hex-Iodin is shown to be worthless for the purpose for which it is advertised. Of the two important ingredients said to be present, iodin and hexa­methylen­amin, only traces could be found of the former while the latter, as has been shown, is incapable of exerting any effect when used as the manufacturers direct.

Formitol Tablets

These tablets are prepared by the E. L. Patch Co., Boston. Each tablet weighs 13¹⁄₂ grs. They have the odor of thymol or menthol and an acid taste and reaction. They are, according to the label:

“For the throat and mouth. Soothing, Astringent, Antiseptic. Rapidly destroys germs of infection, preventing and relieving sore throat and mouth.”

In a circular, it is stated, that one of the qualities of Formitol:

“... is the generation of formaldehyde when in contact with water or the saliva.”

“Besides generating formaldehyde, Formitol, Patch contains astringent, demulcent and soothing ingredients which render the combination unusually effective.”

A bacteriologic report is given in this circular in which it is stated that, in 2¹⁄₂ minutes one Formitol Tablet rendered sterile a plate culture of a “characteristic throat micrococci.” The instructions are to dissolve a tablet in the mouth, slowly, once an hour or a half-tablet every half hour.

The A. M. A. Chemical Laboratory reported that Formitol Tablets contained formaldehyde (or para­form­aldehyde), and ammonium compound, and some hexa­methylen­amin. It is probable that the formaldehyde (or para­form­aldehyde) was produced by the decomposition of hexa­methylen­amin originally present in the tablets but decomposed by long contact with the acid.128

These tablets differ from Hex-Iodin in that they really contain active formaldehyde and, therefore, possibly produce antiseptic effect in test-tube cultures. The conditions in the mouth, however, are very different from those in the test-tube, since in the mouth the formaldehyde would be immediately “bound” or absorbed. The claimed absence of irritation indicates sufficiently the absence of efficient quantities of formaldehyde under clinical conditions.

Cin-U-Form Lozenges

Cin-U-Form Lozenges, manufactured by McKesson and Robbins, New York City, are marketed in bottles of 24 for 25 cents. They have a strong odor of cinnamon, weigh 15¹⁄₂ grs. each, and are acid in taste and reaction. The label states that they contain:

“Cinnamon, Eucalyptus, Formaldehyde and Menthol—all powerful germicides against Influenzal bacilli, but not injurious to the system in this palatable form.”

A circular contains the same statement as to composition and claims further that they:

“... help to prevent the infection of Spanish Influenza, Pneumonia, Grip Colds and to guard against Sore Throat, Tonsillitis, Pharyngitis, etc.”

The A. M. A. Chemical Laboratory reported that Cin-U-Form Lozenges contained some formaldehyde (or para­form­aldehyde) and no hexa­methylen­amin. It is obvious that the mouth and throat cannot be “disinfected” by these lozenges. They would be totally ineffective against bacteria that enter through the nose; they cannot prevent influenza, pneumonia, etc.—(From The Journal A. M. A., Oct. 4, 1919)

LAVORIS

Report of the Council on Pharmacy and Chemistry

Lavoris was considered by the Council in 1913, and its proprietors—the Lavoris Chemical Company—were advised that the preparation was inadmissible to New and Non­official Remedies because of conflict with Rules 1, 4, 6, 8 and 10. No report was published at that time. As the preparation is still widely advertised to physicians, the Council has again examined Lavoris and authorized publication of the following report.

W. A. Puckner, Secretary.

In recent years Lavoris has been widely advertised as “THE IDEAL ORAL ANTISEPTIC,” particularly to the dental profession. A printed card sent out by the Lavoris Chemical Company in 1913 read: “LAVORIS, the Pyorrhea Remedy. The Original ZINC CHLORIDE Mouth Wash. One grain zinc to each ounce.” The card also gave a “formula” to the effect that each pint of Lavoris contained:

Zinc Chloride1.040

Resorcin0.520

Menthol0.400

Saccharin0.195

Formalin0.195

Ol. Cassia Zeyl0.780

Ol. Caryophyl0.195

Advertisements now appearing in medical journals repeat the older “formula” except that resorcin is omitted. The formula while seemingly frank and open is in reality indefinite and misleading in that no denomination of weight is given for the various constituents. It is uncertain, for example, if the figures in the formula are intended to represent grains, grams or percentages of the several constituents. In view of the indefinite statement of composition, a chemical examination of Lavoris was undertaken in the A. M. A. Chemical Laboratory. The report of the laboratory follows:

Zinc.—This was determined electrolytically. Fifty c.c. gave 0.026 gm. zinc and 100 c.c. gave 0.0531 gm. zinc. The average is 0.0526 gm. zinc in 100 c.c. This is equivalent to 0.1102 gm. anhydrous zinc chlorid in 100 c.c.

Chlorid.—After decolorizing some of Lavoris with chlorid-free animal charcoal, the chlorid was determined by the Volhard method. Twenty-five c.c. Lavoris required 4.328 c.c. tenth-normal silver nitrate solution equivalent to 0.01535 gm. chlorid (chloridion) or 0.0614 gm. in 100 c.c. A second 25 c.c. of Lavoris required 4.112 gm. tenth-normal silver nitrate solution equivalent to 0.01458 gm. chlorid (chloridion) or 0.05832 gm. in 100 c.c. Average is 0.05985 gm. This is equivalent to 0.1150 gm. zinc chlorid in 100 c.c. This agrees closely with the foregoing zinc determination.

Resorcin.—The method of the U. S. Pharmacopeia was used. The total bromin absorption of 25 c.c. Lavoris was 3.68 c.c. tenth-normal bromin solution. This would be equivalent to 0.00675 gm. resorcin in 25 c.c. or 0.02700 gm. in 100 c.c. In a duplicate test, 25 c.c. Lavoris required 3.8 c.c. tenth-normal bromin solution equivalent to 0.00697 gm. resorcin or 0.02788 gm. in 100 c.c. Since oil of cinnamon absorbs bromin, 50 c.c. of Lavoris was boiled until very little or no odor of the oil was noted, keeping the volume nearly constant by adding a little water from time to time, and the bromin absorption then taken. In one experiment, 0.36 c.c. of tenth-normal bromin solution was consumed, and in a duplicate no bromin was absorbed. This shows the absence of resorcin.

Residue.—On evaporating 25 c.c. Lavoris on a steam bath and subsequent drying of the residue at 100 C., 0.0455 gm. of residue was obtained. This is equivalent to 0.1820 gm. in 100 c.c.

Saccharin.—Saccharin was detected in the residue and ether-extract of the residue by its intense sweet taste when a little sodium bicarbonate was added to it.

Formaldehyd.—This could be detected by the Jarrison test. The color was not very pronounced and the quantity of formaldehyd was small.

Oil of Cinnamon.—The odor and taste of Lavoris is characteristic of cinnamon.

Menthol and Oil of Cloves.—The odor of menthol and of oil of cloves could not be detected, but no tests were made to demonstrate their presence.

The analysis thus indicates that the Lavoris of today contains no resorcin but does contain a small amount of formaldehyd, a little saccharin, and oil of cinnamon (menthol and oil of cloves could not be detected by the odor, but were not tested for). The analysis showed that the principal constituent of Lavoris is zinc chlorid, of which there is about 0.1 gm. per 100 c.c. (about ¹⁄₂ grain to the ounce).

The amount of zinc chlorid given in the published formula, i. e., 1.04, is meaningless because the unit of weight or measure is not given; furthermore, the analysis shows that it is inaccurate for any unit of weight that might be assumed from the published figures. Since the amount of the most active medicinal ingredient is both indefinite and inaccurate, the composition of the preparation is essentially secret. Lavoris is indirectly advertised to the public by having included in the package a circular giving a list of diseases for which the preparation was recommended. The combination of zinc chlorid, formaldehyd and oil of cinnamon (assuming the menthol and oil of cloves to be present as flavors) in a mixture is irrational and likely to lead its users to ascribe a false and exaggerated value to the preparation. The name is objectionable in that it does not indicate the composition of the potent ingredients of the mixture, but instead suggests its use as a mouth wash.

From a standpoint of public safety, the most serious objection to Lavoris, however, lies in the many unwarranted therapeutic claims and suggestions. It is generally held that zinc chlorid solutions which possess a strength of from 1 to 200 up to 1 to 500 exercise a weak antiseptic action. The strength of zinc chlorid in Lavoris is approximately 1 to 1,000. The directions for its use recommend that Lavoris should be diluted. A dilution of 1 to 4 is recommended for a variety of mouth conditions while for cystitis irrigations and as a vaginal douche, it is recommended that one tablespoonful be added to a quart of warm water or salt solution. The strength of zinc chlorid in the last suggested dilution would approximate 1 to 64,000. It is evident that no antiseptic action could be expected from such dilutions.

The recommendation that diluted Lavoris be used for the treatment of coryza, nasal catarrh, hay fever, inflamed eyes, hemorrhoids and leucorrhea is objectionable and irrational. Especially dangerous is the recommendation that members of a family exposed to diphtheria or scarlet fever should use Lavoris freely as a preventive. Such recommendations can but give a false sense of security and lead to the neglect of proved methods for preventing the spread of these diseases. Equally unwarranted is the recommendation that in gonorrhea one teaspoonful of Lavoris to eight of warm water be used with a blunt end syringe.

The use of Lavoris as recommended would not only prove valueless in many instances but might lead to serious consequences because really valuable methods of prevention or treatment might be neglected. For these reasons the preparation is in conflict with Rule 6.

The Council declared Lavoris ineligible for New and Non­official Remedies.—(From The Journal A. M. A., Nov. 1, 1919)

MEDINAL

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Medinal (Schering and Glatz, Inc.).

W. A. Puckner, Secretary.

Medinal is a proprietary name applied to barbital sodium (sodium diethyl­barbiturate) the sodium salt of barbital (di­ethyl­barbituric acid). The latter was first introduced as Veronal.

Medinal was deleted from New and Non­official Remedies in 1916 because the advertising issued by Schering and Glatz (who then acted as agents for Chemische Fabrik auf Actien vorm. E. Schering, the German manufacturer) contained misleading and unwarranted therapeutic claims. The Council did not publish its report because by the time the report was ready for publication the product was practically off the American market, and it was hoped that when Medinal again became available, Schering and Glatz would revise the claims and thus permit its reacceptance.

Medinal, said to be manufactured in the United States, is now marketed by Schering and Glatz, Inc. In October, 1918, the firm sent to the Council a typewritten copy of a proposed circular for Medinal. The firm was informed that this leaflet was subject to the objections that had been raised when Medinal was deleted from New and Non­official Remedies. In April, 1919, the firm submitted a printed circular which it was sending out. This contained numerous misleading statements, among them, these:

“Medinal removes its [Di­ethyl­barbituric acid] one objectionable feature—insufficient solubility—and thus fulfills the three prerequisites of a truly rational hypnotic: Quick absorption, insuring prompt action, rapid and complete excretion, affording protection from cumulative toxic after effects, and the choice of rectal and subcutaneous administration.”

There is no justification for the claim that diethylbarbituric acid (barbital) has only one objectionable feature and that a minor matter of “insufficient solubility.” The Council has called the attention of Schering and Glatz, Inc., to the fact that the difference in the time of absorption between Medinal (barbital sodium) and barbital is, at the most, but one of minutes and that there is no evidence that Medinal is excreted more rapidly than barbital. Hence the claims that the danger of toxic side-actions and that cumulative after-effects are avoided in this product, are wholly unwarranted.

It is also claimed, and the claim is unsupported by satisfactory evidence, that Medinal is useful in the insomnia of tuberculosis in which condition it is said to have a double advantage owing to its favorable effects on the night-sweats. It is claimed that Medinal is used in the withdrawal treatment of morphin addiction with great success; there is no evidence that Medinal has any special usefulness in this treatment of the morphin habit. It is claimed further that success has been reported with Medinal in the treatment of whooping cough. The Council knows of no satisfactory evidence to show that Medinal is of special value in whooping cough; on the contrary, it is capable of doing a great deal of harm. The recommendations that Medinal be used for the control of labor pains and in acute neuralgic pains that resist other forms of treatment are wholly unwarranted as the value of the drug in such conditions is inherently improbable and until satisfactory evidence in support of them is forthcoming, must be deemed misleading.—(From The Journal A. M. A., Nov. 15, 1919)

OMISSION OF COTARNIN SALTS (STYPTICIN AND STYPTOL) FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

Salts of the base cotarnin have been used as local and systemic hemostatics. The hydrochlorid was first introduced as “Stypticin,” and is now in the pharmacopeia as cotarnin hydrochlorid (Cotarninae Hydrochloridum, U. S. P.). The phthallic acid salt of cotarnin—cotarnin phthallate—was introduced as “Styptol.” Both Stypticin and Styptol were admitted to New and Non­official Remedies. In 1918 the Council voted to omit Stypticin because the former American agents were no longer offering it for sale. Styptol was retained and is described in N. N. R., 1919.

As was pointed out in the description (N. N. R., 1918), the evidence for the usefulness of the cotarnin salts has been contradictory and unsatisfactory; but since the available data against the efficiency were at least equally unreliable, the Council deemed it best to retain them in N. N. R. pending a thorough investigation of the subject. This was undertaken by P. J. Hanzlik, at the suggestion of the Therapeutic Research Committee of the Council.

A reliable judgment of hemostatic efficiency can be formed only on a basis of strictly controlled conditions, which can best be furnished in the laboratory. Hanzlik repeated the principal experiments published by previous investigators, and applied a number of new or improved methods. The results (published in the Journal of Pharmacology and Experimental Therapeutics 10:523, 1918; 12:71, 1919) show the following:

Direct Application to Wounds.—The widely quoted results of the gynecologist K. Abel, on the footpad of cats, were found to be quite unreliable. When the experiment is properly controlled, the results are either negative or the bleeding may be increased. Quantitative experiments on wounds of the footpad of dogs showed that cotarnin invariably increased the bleeding. Equally negative or unfavorable results were obtained with wounds to the comb of roosters, and to the liver and spleen.

Direct Action on Vessels.—The results of perfusion experiments were variable, but, in general, showed a vasodilation action instead of constriction. This holds true also of the uterine vessels. The vessels in the living animal (rabbit’s ear) were also unaffected.

Systemic Administration.—The bleeding from an irrigated wound was not modified directly by intravenous injection of cotarnin salts, but varied merely with the state of the blood pressure.

The evidence for the inefficiency of cotarnin salts as hemostatics seemed so conclusive as to warrant the Council in rescinding the acceptance of Styptol, and directing the omission of the general article on cotarnin salts and the description of Styptol from New and Non­official Remedies.—(From The Journal A. M. A., Nov. 22, 1919)

MICAJAH’S WAFERS AND MICAJAH’S SUPPOSITORIES

Report of the Council on Pharmacy and Chemistry

“Micajah’s Medicated Wafers” and “Micajah’s Suppositories,” sold by Micajah & Co., Warren, Pa., are declared inadmissible to “New and Non­official Remedies” because (1) their composition is essentially secret (Rule 1); (2) name of neither of these mixtures is indicative of its composition (Rule 8); (3) of exaggerated and unwarranted therapeutic claims (Rule 6), and (4) the therapeutic advice which accompanies the trade packages constitutes an indirect advertisement to the public (Rule 4).

W. A. Puckner, Secretary.

Micajah’s Medicated Wafers (formerly called “Micajah’s Medicated Uterine Wafers”) were analyzed in the A. M. A. Chemical Laboratory in 1910. They were found to consist essentially of dried (“burnt”) alum, boric acid and borax, in approximately the following proportions:

Alum, dried59.86 per cent.

Borax, dried15.62 per cent.

Boric acid 5.67 per cent.

Water of hydration18.85 per cent.

There are a number of drugs that are more or less effective in the treatment of local lesions of mucous membranes and the skin. They are classed as astringents. Among these are included alum, borax and boric acid. Every physician has used them. To say that a wafer consists of alum, borax and boric acid inspires but little awe. But there is something much more mysterious and impressive in declaring that a wafer “consists of an astringent and antiseptic base, in which are incorporated certain medicaments which both locally and after absorption, contribute to the astringent, antiphlogistic, depletive, soothing and healing action of the product.” This gives the impression that some powerful and almost incomprehensible factors are at work. Yet, after all is said and done, the substances contained in Micajah’s Medicated Wafers are just the homely old alum, boric acid and borax.

In addition to “Micajah’s Medicated Wafers,” Micajah & Co. also put out “Micajah’s Suppositories for Hemorrhoids.” These have been examined in the A. M. A. Chemical Laboratory and, like the “Medicated Wafers” have been found to contain alum, boric acid and borax—and these substances practically alone—incorporated in cocoa butter. The company claims that “to these have been added Ammonii Ichthyo­sulphonate, Balsam of Peru, Ext. Belladonae.” The A. M. A. chemists report, however, that if extract of belladonna is present at all it is in amounts too small to be detected by the method commonly employed in the chemical examination of alkaloidal drugs. The chemists report further that while ammonium ichthyo­sulphonate and balsam of Peru both have a decided odor and are dark in color, the suppositories have but little color and the odor of the cocoa butter that forms their base is not covered by these drugs; obviously, therefore, if ammonium ichthyo­sulphonate and balsam of Peru are present at all it is in amounts utterly insufficient to exert any therapeutic effect.