DR. DE SANCTIS’ RHEUMATIC AND GOUT PILLS
Dr. DeSanctis’ Rheumatic and Gout Pills are sold by Edward Cleaver, 13 Clerkenwell Road, London, England. The American agents are E. Fougera and Co., Inc., New York. The package is a round pill box and contains twelve pills and a circular, which directs that one pill be taken every eight hours until relieved. In the package there is also a circular advertising Dr. DeSanctis’ Gout and Rheumatic Paint, with directions for its use. On the cover of a box, which contained six of the retail packages, is the statement that these pills have been in general use for nearly 100 years, and that their sale has been built up without advertising.
DeSanctis’ pills are round, uncoated, and have a light brown color. There was some variation in the color of different lots, one lot in particular being gray rather than brown. A little arrowroot starch was found in each box, this evidently having been used as a dusting powder. The pills were very hard, rather brittle, but quite difficult to powder. The pills were not readily disintegrated by water or diluted acids, even when warmed, but when warmed with a dilute sodium hydroxid solution they readily disintegrated.
Ten pills weighed 3.213 gm., an average of 0.3213 gm., or 5 grains. The arrowroot starch used as a dusting powder was removed as completely as possible by rolling the pills in a cloth. Several dozen pills were then powdered and the powder thus obtained used for the analysis.
A microscopic examination of the powder showed powdered colchicum seed in abundance and also traces of arrowroot starch, no doubt from that used as the dusting powder.
Since colchicum seed was so abundant, the powder was assayed by the U. S. Pharmacopeial method for colchicum seed (U. S. P. IX, p. 120), slightly modified so that less of the powdered pills than directed there could be used. In one assay 3.75 gm. gave 0.0204 gm. of colchicin or 0.54 per cent. In a duplicate, 5 gm. gave 0.0234 gm. of colchicin or 0.47 per cent.; average 0.5 per cent.
The alkaloid obtained had the characteristic appearance and odor of colchicin when separated from the seed under these conditions. The solution in water and acid was yellow; the aqueous solution was intensely bitter, and the yellow color intensified with acids. The dry residue became intensely yellow with concentrated sulphuric acid; with nitric acid it became violet turning to yellow, and with concentrated sulphuric acid and potassium nitrate it gave a yellowish green color, turning to violet and finally to a wine color. All these reactions are typical of colchicin.
From 1 gm. of the powdered pills there was obtained 0.0425 gm. of ash, or 4.25 per cent.
When the powdered pills were extracted with chloroform in a Soxhlet apparatus, a very uniform quantity of extract was obtained. From 5 gm. there was obtained, in one case, 0.581 gm.; in another, 0.5755 gm., and in a third, 0.588 gm., the average being 0.5815 gm. or 11.63 per cent.
On still further extracting with alcohol, a small amount of extractive was obtained, the amount depending on the length of time the extraction was continued.
On extracting with hot water the residue left after exhaustion with chloroform and with alcohol, a further extract was obtained. In one case, it amounted to 0.4763 gm. or 9.53 per cent., and in another case it amounted to 0.470 gm., or 9.40 per cent.; average 9.47 per cent.
In attempting to dry the pills or the above-mentioned chloroformic extract at 100 C., a crystalline sublimate was obtained which had the odor of benzoic acid. The crystals were acid, their neutral solution gave a flesh-colored precipitate with ferric chlorid, and they melted at 120–121 C. This crystalline substance appeared to be benzoic acid.
The quantity of benzoic acid in this extract was determined by heating it to about 140 C. A current of air was drawn through the flask and the sublimed benzoic acid collected in a cooled tube. The benzoic acid was washed out of the tube with neutral alcohol, and the solution was titrated with tenth normal potassium hydroxid. In one case, 11.25 c.c. of tenth-normal alkali was used, indicating 0.1373 gm, of benzoic acid; in another, 12.27 c.c., indicating 0.1498 gm. of benzoic acid; average 0.1436 gm., or 2.87 per cent. In a third case the temperature reached 250 C., and there was some decomposition of the fat in the flask and some colored material distilled over. For this sublimate 15.54 c.c. of tenth-normal alkali were required.
After evaporating the alcohol and acidulating the solutions obtained in the previous experiments, the benzoic acid was extracted with chloroform. In the first case, 0.1383 gm. was obtained; in the second, 0.1541 gm.; average 0.1462 gm., or 2.92 per cent. of benzoic acid.
When the original chloroformic extract was heated until all of the benzoic acid had been driven off, the residue had the appearance of a semisolid fat. It compared quite closely in color, odor, etc., with the fatty material obtained by extracting colchicum seed with chloroform, although the odor was more suggestive of oleic or stearic acid. It was distinctly acid, which is also true of the fatty material obtained from a sample of colchicum seed.
The extract obtained with hot water was light yellow; gummy, at first, but dried to a glass-like brittle mass. It had a slight burned-sugar odor and taste, and was neutral in reaction. It was strongly dextrogyrate and at once reduced Fehling’s solution as well as alkaline silver nitrate solution. On boiling with potassium hydroxid solution, it turned deep red. It also gave the Molisch carbohydrate reaction, and the ozazone test in seventeen minutes as described in Mulliken (Identification of Pure Organic Compounds, Ed. 1, 1905, p. 26). These are all characteristic reactions of lactose or milk sugar.
From this examination we conclude that DeSanctis’ pills contain powdered colchicum seed, benzoic acid, and sugar of milk. There is also present fatty material which resembles the fat of colchicum seed, but may be, in part, added fatty acid. The percentage of colchicin found (0.50) is about that of a good quality of colchicum seed, the U. S. Pharmacopeial standard being not less than 0.45 per cent. Since the pills contain material other than colchicum seed, this assay would indicate a colchicum seed of high alkaloidal content, or the possible reinforcement of the pills with colchicum extract or colchicin.
The amount of benzoic acid, 2.92 per cent., or about 1⁄7 grain per pill, is insignificant from a therapeutic standpoint, since an average dose is 0.5 gm., or 8 grains. Fatty acids, and the fatty matter from colchicum seed are inert, at least in the quantities found here. The only office which fatty acids might perform, would be to give the pills an enteric quality, preventing their absorption until they reach the intestine. The sugar of milk, about 10 per cent., or 1⁄2 grain per pill, no doubt is simply an excipient.
DeSanctis’ pills are therefore essentially 5 grain doses of powdered colchicum seed, of which the average dose is 0.2 gm., or 3 grains (U. S. P. IX, p. 120).
The Journal in presenting the facts contained in the above report made the following comments:
“Here then, we have sold for self-medication an extremely poisonous drug, with no warning of the risk the public runs in using it. While the directions call for “one pill every eight hours until relieved,” it is notorious that the public takes the attitude toward “patent medicines” that, if a little is good, more is better, and the average user of remedies for self-treatment is likely, unless there is some warning, to use his own discretion as to the amount taken.
“The individual dose is above that of the average recommended in the United States Pharmacopeia. Colchicum or its alkaloids—or for that matter, any drug as toxic as colchicum—have no place in preparations of the home-remedy type. In the case of all “patent medicines,” public interest demands that the full quantitative formula of the therapeutically active ingredients should be given on the label, for when the public prescribes for itself, it has a right to know what it is taking. Unfortunately, public interest clashes with vested interests and, as usual, vested interests get the better of it. In the case of such dangerous preparations as DeSanctis’ pills, if their sale is to be permitted at all, not only should the names and quantities of all therapeutically active ingredients in the mixture be given, but the law should require that the word Poison be plainly printed on the label.”—(Abstracted from The Journal A. M. A., July 19, 1919.)