Note on Tincture of Strophanthus.
By W. MARTINDALE.
Read at an Evening Meeting of the Pharmaceutical Society of Great Britain, Wednesday, November 17.
The researches of Drs. Fraser and Ringer on strophanthus, the kombé arrow poison, and the publication by the former of his paper, read at the Cardiff Meeting of the British Medical Association (Brit., Med. Journ., vol. ii., 1885, p. 904), have lately attracted much attention to this drug. Unfortunately a supply of it is difficult to obtain. A paper on the species of strophanthus used in medicine was read at the Evening Meeting here on March 10, 1886, by Mr. Holmes, (Pharm. Journ., 1886, p. 778, AM. JOUR. PHAR. 1886, 406). Since then a supply of the drug has been received by Messrs. Christy & Co., and a formula for the tincture has been published by Messrs. Burroughs, Wellcome & Co. (Pharm. Journ., 1886, p. 304, A. J. P. 1886, 405), on the authority of Dr. Fraser. It directs that 1 ounce of the seeds, first deprived of their oil or fat by means of ether, is to be percolated with rectified spirit to produce 8 fluidounces of tincture. As pharmacists have looked with some suspicion on the employment of ether for the extraction of the fixed oils from such drugs before making pharmaceutical preparations of them, for example in the present process for making extract of stramonium and in the now discarded process for making liquid extract of ergot, I therefore wrote to Dr. Fraser pointing this out, stating my fear that some of the activity of the strophanthus seeds might be removed by the ether, and mentioning also that as there was a tendency to decimal proportions for these preparations, I thought that a 1 in 10 tincture would be preferable. I concluded by saying that I should be glad to have a reply from him in corroboration or otherwise of the formula published by the above-mentioned firm. He replies:
"The active principle of strophanthus is practically insoluble in ether, and therefore it is quite a suitable solvent for the oil whose presence is objectionable in the tincture.
"I have used a tincture of various strengths. Seeds alone without hairs 1 in 8 of rectified spirit was adopted because of its being the strength of tinct. of digitalis, and the dose of such a tincture is 2 to 4 minims.
"As this dose is inconveniently small, especially for children, I now generally use a tincture of half the strength, 1 in 16.
"One in 10 would not get over this difficulty. The dose of the tincture of 1 in 16 would, of course, be 4 to 8 minims.
"I have not seen the letter of Burroughs & Wellcome to which you refer."
He further writes:
"Although the pods contain active principle, the relation of a tincture obtained from them to a tincture from the seeds has not been determined. The two should not therefore be used together. The preparation I have used in therapeutic work has always been the tincture from the seeds. I do not know what the dose would be of a tincture from the combined pods and seeds. I think also the seeds freed from their comose appendices should alone be used. In reference to the preliminary extraction with the ether, it is obvious the ether should be washed to remove spirit."
This is so far conclusive, and as the results of other therapeutic observers will have to be compared with Dr. Fraser's, when tincture of strophanthus is ordered pharmacists must supply the tincture of the seeds only, deprived of oil. Still, as the drug is scarce and costly it is well that we should examine it and try to utilize all the parts of it that possess activity. While awaiting Dr. Fraser's reply I prepared a little tincture of the bruised natural seeds by percolating one part with rectified spirit q. s. to produce 8 fluid parts. It is labelled a, is of a yellowish-green color and has a characteristic bitter taste. I did not examine the marc of this to notice if it was exhausted.
Nearly one-half the weight of the pods now offered for sale consists of the linings of the pericarps, one-third (nearly) is seeds, and about one-fifth is hairs.
In preparing Dr. Fraser's tincture, the seeds in coarse powder were percolated with about five times their weight of ether, specific gravity 0.720 (the rectified washed methylated). A deep emerald-green liquid having a claret-colored fluorescence was obtained. It has deposited a small quantity of crystalline sediment. Evaporation of a part of it shows that the seeds yield 27 per cent. of dark green ethereal oil or oily extract, which is very bitter in taste, and only slightly soluble in rectified spirit. After the ether was evaporated from the marc this was again slowly percolated with rectified spirit, 1 to produce 8 parts of yellowish-green colored tincture marked b1, but this is much paler than tincture a. Percolation was continued fractionally to produce a second 1 in 8 percolate, marked b 2, and a third, 1 in 4, marked b 3; the last two percolates are practically colorless, but bitter, and although their specific gravity is the same as the spirit used in making them, yet the marc is still bitter. The specific gravity of the first percolate is nine points higher. Mixed, these three percolates would produce a 1 in 20 tincture.
The depurated tincture b 1, on addition to water, of course forms; a clear mixture; but tincture a only causes a slight opacity when it is mixed with water—very little more than the same quantity of tincture of orange peel would cause.
I also percolated a separate tincture of the powdered pericarp lining, 1 in 8 with rectified spirit, marked d. It is pale greenish-yellow in color, has the same but less bitter taste than the tincture b 1, and is five points lower in specific gravity. The marc left was still bitter. I likewise prepared a tincture of the hairs 1 in 8, with rectified spirit, marked c. It has the yellowish-green color of tincture a, and has a similar bitter taste, although according to Messrs. Hardy & Gallois (Pharm. Jour., 1877, p. 756; Am. Jour. Ph., 1877, p. 402) the hairs only contain ineine, a crystalline principle which has not the same physiological action as strophanthin contained in the seeds; this stops the heart's action when its solution is injected into a frog, which ineine does not.
I give these results of my experiments, expecting to elicit expression of opinion as to what formula might eventually be adopted. The present one, Dr. Fraser himself acknowledges, produces a preparation too concentrated for practical use. As the drug arrives with a variable amount of the pericarp adhering, and this generally in bad condition, and as the hairs are said to possess different properties to the seeds, I think the seeds alone should still be used, as they only can be relied upon to produce an uniform tincture. The other portions possessing activity might be economized for preparing the active principle. Care must be taken in handling the drug and its preparations, as they act as topical irritants, to the mucous membrane particularly.
Since writing the above Dr. Ringer has kindly tried the ethereal oil on frogs for me and finds that although not inert it does not possess much activity, not nearly so much as a 1 per cent. solution of the arrow poison.
Mr. T. R. Bradford, of University College, to whom I gave samples, also writes:—
"I have performed some experiments with the tinctures of the seeds, pods, and hairs, and I find them all active; but that obtained from the hairs is the weakest, and that from the seeds is the strongest in arresting the movements of the frog heart. They are also all of them powerful muscle poisons, particularly the pod tincture, but of course to, decide this more experiments would be necessary."—Phar. Jour. and Trans., Nov. 20, 1886, p. 411.