TRI-ARSENOLE, L. O. COMPOUND NO. 1 AND L. O. COMPOUND NO. 2
Report of the Council on Pharmacy and Chemistry
Tri-Arsenole.—According to the advertising of the Medical Supply Company of Atlanta, Ga., “Tri-Arsenole” is “Merco-Arseno-Benzo-Chloride,” and the claim is made:
“This compound is the result of many years’ research. The toxicity has been fully tested upon animals before using clinically, the latter having proven such complete success, we take pleasure in presenting it to the public ...”
“The manufacturers of TRI-ARSENOL, before placing it upon the market, tested it biologically.”
Tri-Arsenole is “recommended and suitable for the treatment of primary, secondary, tertiary and hereditary syphilis. It has also been found very useful in pellagra and malaria.” The preparation is supplied in ampules containing varying amounts of the dry substance. It is to be dissolved in water and is to be administered intravenously. In the advertising attention is called to the yellow color of Tri-Arsenole; this, and the style of package suggest that it is a preparation similar to salvarsan.
In reply to a request sent the Medical Supply Company for the quantitative composition and chemical formula of the compound “Merco-Arseno-Benzo-Chloride” and for the details of the biologic test by which its toxicity is claimed to have been determined and evidence for its efficiency, the following statement was received:
| “Tri-Arsenole No. 1 equals to each Ampoule, | gr. |
Sodium chlorid | 41⁄2 |
Hydrarg chlor.-cor. | 1⁄4 |
Arsenous acid | 1⁄4 |
Sodium benzoate | 4 |
Hydrastin (resinoid) | 2 |
| Tri-Arsenole No. 2 equals to each Ampoule, | |
Sodium chlorid | 4 |
Hydrarg chlor.-cor. | 1⁄2 |
Arsenous acid | 1⁄2 |
Sodium benzoate | 4 |
Hydrastin (resinoid) | 2 |
| Tri-Arsenole No. 3 equals to each Ampoule, | |
Sodium chlorid | 31⁄2 |
Hydrarg chlor.-cor. | 3⁄4 |
Arsenous acid | 3⁄4 |
Sodium benzoate | 4 |
Hydrastin (resinoid) | 2 |
| Tri-Arsenole No. 4 equals to each Ampoule, | |
Sodium chlorid | 3 |
Hydrarg chlor.-cor. | 1 |
Arsenous acid | 1 |
Sodium benzoate | 4 |
Hydrastin (resinoid) | 2 |
The request for information regarding the animal experiments said to have determined the toxicity was ignored, nor were references supplied to clinical reports demonstrating the value of the product.
The Council declared Tri-Arsenole inadmissible to New and Nonofficial Remedies because of conflict with the rules as follows:
In the absence of details of the method used, the claim that the preparation has been tested biologically is in conflict with Rule 2, which requires that for preparations claimed to be physiologically standardized the method of testing must be published so as to permit of control by independent investigators.
The claims that “Merco-Arseno-Benzo-Chloride” is “the result of many years research,” that its “toxicity has been fully tested upon animals before using clinically” and that clinical use has “proven such complete success” have not been substantiated by evidence and must be held as unwarranted.
The name is in conflict with Rule 8, which requires that pharmaceutical mixtures shall bear names descriptive of their composition. Further, the name “Tri-Arsenole” by its similarity to Diarsenol, the Canadian brand of arseno-phenolamin hydrochlorid, suggests that this pharmaceutical mixture is a chemical compound similar to salvarsan. Moreover, the danger of confusion is increased by the addition of the hydrastis preparation which imparts a yellow color like that of salvarsan to the solution obtained when the colorless mercury and arsenic compounds of the mixture are dissolved. Again, the synonym “Merco-Arseno-Benzo-Chloride” conveys the false impression that Tri-Arsenole is a definite chemical compound.
The label does not declare the poisonous constituents claimed to be contained in the mixture; namely, “arsenous acid” and corrosive mercuric chlorid (Rule 7).
There is no evidence that arsenous acid (arsenic trioxid) used intravenously is efficient and safe as a spirocheticide, and the administration of this drug in conjunction with mercuric chlorid in fixed proportion is irrational and dangerous—particularly so because of the implied similarity of Tri-Arsenole to arsenphenolamin hydrochlorid (Salvarsan, Diarsenol) (Rule 10).
L. O. Compound No. 1 and L. O. Compound No. 2.—In submitting these preparations to the Council, the Medical Supply Company stated that “No. 1” was “composed of the following ingredients; chloral, camphor, menthol, iodin, and oil of gaultheria, incorporated in a fatty base. Each ounce contains fifteen grains of chloral hydrate, nine grains of resublimed iodine.” “No. 2” was said to have the same composition as “No. 1” except that the oil of gaultheria had been omitted. The Medical Supply Company was informed that the rules of the Council required declaration of the amounts of each therapeutic constituent of pharmaceutical mixtures and that, therefore, in addition to the information furnished the amounts of camphor, menthol and oil of gaultheria should be given for “No. 1” and the amount of camphor and menthol for “No. 2.” The following reply was received:
| “L. O. Compound No. 1 equals to each Tube, | |
Chloral hydrate | gr. 15 |
Camphor | gr. 22 |
Menthol | gr. 71⁄2 |
Iodin (resublime) | gr. 32⁄3 |
Oil of gaultheria | m. 3 |
Petrolatum, q. s. | oz. 1 |
| L. O. Compound No. 2, |
| The same as above formula for L. O. C. No. 1, except the oil of gaultheria which is omitted.” |
It should be noted that when the preparations were submitted each ounce of the preparation was claimed to contain 9 grains of iodin, while in the subsequent letter the company declares that they contain only 32⁄3 grains to the ounce. If it be assumed that the unit intended is the avoirdupois ounce, the preparation should contain 2.06 per cent. of iodin according to the first statement and 0.84 per cent. of iodin according to the second statement. While the dark color of the preparations suggested the presence of appreciable amounts of free iodin, the A. M. A. Chemical Laboratory reported that an examination of the specimens submitted by the Medical Supply Company showed that “No. 1” and “No. 2” each contained but 0.033 per cent. of free iodin; hence both preparations are in conflict with Rule 1.
For both preparations the labels suggest their use for the treatment of “septic wounds, burns, pustular processes of all varieties, and especially bronchial troubles.” This constitutes a conflict with Rule 4. Regarding No. 1 the advertising circular included with the trade package asserts:
“Its merits have been practically demonstrated in the following conditions. We invite your especial attention to its use in diseases of the thoracic cavity, especially Bronchitis and Pneumonia, Rheumatism, Lumbago, Migraine, Neuralgia, Orchitis, Balanitis, enlarged glands or any disturbance of the lymphatic system, anti-galactagogue, or wherever analgesic action is required.”
“No. 2” is said to be especially adapted to the needs of the surgeon, it “can be applied in any wound either aseptic or infected.” It is asserted that the usual method of preparing patients for operation may be discarded and that patients may be operated on after application of this ointment:
“... We have no other preparation to-day which serves the purpose of L. O. Compound in operative and post operative treatment.
“It is a powerful antiseptic and germicide combining anesthetic, analgesic and alterative properties.”
After attempting to discredit the approved methods of preparing the field for surgical operations, the advertising circular continues:
“Method of today: A liberal amount of L. O. Compound No. 2 is applied to the intended area of operation, massage thoroughly until absorption is complete. Patient is ready for operation ...”
Both products are in conflict with Rule 6. Further, as the names of these pharmaceutical mixtures are not descriptive of their composition, they also conflict with Rule 8.
The use of complex mixtures such as these is irrational and leads to misplaced confidence on the part of the physician; particularly when, as in this case, neither the label nor the advertising matter gives the necessary information regarding the composition of the preparations further than that, in accordance with the requirements of the Federal Food and Drugs Act, the amount of chloral is declared (Rule 10).
The Council declared L. O. Compound No. 1 and L. O. Compound No. 2 inadmissible to New and Nonofficial Remedies for conflict with Rules 1, 4, 6, 8 and 10.
The Council’s consideration of Tri-Arsenole, L. O. Compound No. 1 and L. O. Compound No. 2 was based on information received from the Medical Supply Company, the correspondence being signed “Medical Supply Co., per Dr. H. E. Pontius.” The findings having been sent to the Medical Supply Company, the following reply was received:
(June 27, 1917) “Replying to your registered letter of this A. M. relative to the Medical Supply Company’s products, will state that the party furnishing you with such information as you have in hand was misinformed. He is no longer with this company and whereabouts unknown.
Respectfully,
Medical Supply Company,
(Signed) W. B. Lingo, President.”
The Medical Supply Company then was asked to point out any statements occurring in the report, as submitted, which the company considered to be inaccurate; but no reply has been received to this request. The advertising sent out by the Medical Supply Company during the last part of August contained essentially the same statements and claims as those to which reference is made in the preceding report. A qualitative examination of Tri-Arsenole made in the A. M. A. Chemical Laboratory indicated the presence of sodium, mercury, arsenic, chlorid, benzoate and a hydrastis preparation. Quantitative determinations were not made as there was no guarantee that an analysis of the present supply would indicate the composition of that marketed later on.
In view of the statement of the president of the company, that the information submitted in the letters from the Medical Supply Company was inaccurate, Tri-Arsenole and L. O. Compound must definitely be placed with preparations, the composition of which is not divulged by their owners; hence Tri-Arsenole as well as L. O. Compound No. 1 and L. O. Compound No. 2 are in conflict with Rule 1.—(From Reports of Council on Pharmacy and Chemistry, 1917, p. 156.)