Extraction of Colchicia from the Seed.
BY LEMUEL I. MORRIS.
Read at the Pharmaceutical Meeting, December 21st.
The powdering or grinding of colchicum seed has always been a source of much labor and annoyance to the pharmacist, and to overcome the difficulty, the purchasing of seed already ground has often been resorted to, a practice which does not commend itself to the profession, for the reasons that the powder is more expensive and can be very easily adulterated.
Dannenberg ("Phar. Ztg." Oct. 30, 1880) has recently, in answer to an article by Dr. Molz ("Deutsch. Amer. Phar. Ztg."), shown that he obtained results contradicting the conclusions of the latter, who stated that colchicum seed, when more than a year old, was nearly worthless, and that colchicia could be extracted only by a strong alcoholic or acidulated menstruum, while he (Dannenberg) obtained the alkaloid reaction after boiling the seed, which was not less than five years old, for only a few moments in pure water. These different statements have led to some discussions on the subject and a desire to further investigate the matter.
To Dr. Hübler ("Arch. der Pharm.," 1865), it seems, belongs the credit of making the first statement that colchicia could be wholly extracted without powdering the seeds, by digesting them for some time in a hot 90 per cent. alcoholic menstruum. When afterwards powdered, and treated like the whole seed, it was found that the alkaloid had been entirely removed, and that very little if any soluble matter was extracted by the menstruum from such powdered seed.
Mr. Rosenwasser, in 1877 ("Amer. Jour. Phar."), after some experiments, found that only one-third of the colchicia was removed by macerating the whole seed, in officinal menstrua, for some time. Had he employed a hot menstruum, he would have obtained different results.
Some of the whole seeds were obtained from a cabinet specimen of Prof. Maisch's, which has been in his possession for over ten years. Of this sample, 50 grams were macerated in cold dilute alcohol (sp. gr. .941) for three days; a portion of the tincture was then evaporated to dryness, the residue treated with alcohol, again evaporated to dryness, treated with water, and filtered. The filtered liquid was tested with Mayer's test, after the addition of a few drops of nitric acid, when a yellow precipitate was immediately produced. The seeds were then well drained, and treated again with a fresh portion of the menstruum, when an additional amount of alkaloid was obtained. On treating them in a like manner for the third time, no more alkaloid was obtained.
They were then digested in dilute alcohol, with a moderate heat, for three hours, and on applying the usual tests a considerable amount of colchicia was found to be present. After well draining, they were again subjected to the action of heat and dilute alcohol, but no alkaloid was found present on testing the filtered liquid.
The seeds were now well drained, powdered and macerated in cold dilute alcohol for three days, when on testing a portion of the menstruum none of the alkaloid was found present, and the result was not altered by digesting in the same menstruum, with a moderate heat, for three hours, although a considerable amount of soluble matter was extracted. The tincture obtained from the cold maceration was evaporated to the consistence of an extract, and weighed 4.806 grams — 9.61 per cent. It was treated with alcohol until all the soluble matter was dissolved, the alcoholic solution was evaporated to dryness, the residue treated with water, the aqueous solution filtered, and the alkaloid precipitated by Mayor's test; the precipitate, carefully washed and dried, weighed .093 gram — .18 per cent.
The decoction obtained from digesting the seeds with hot dilute alcohol was then evaporated to the consistence of an extract, and weighed 2.0006 grams — 4.01 per cent. The extract was treated in a similar manner as the preceding, and the colchicia precipitate was found to weigh .161 gram — 0.32 per cent., showing that nearly two-thirds of the active principle was extracted by the hot, and only one-third by the cold menstruum, the latter being the proportion also obtained by Mr. Rosenwasser. In all cases, the extracts and precipitates containing the alkaloid gave the characteristic colchicia reaction with sulphuric acid and potassium nitrate.
Some of the whole seeds were then boiled in pure water; on testing the filtered liquid, colchicia was found present. The seeds were then powdered, again boiled in water, when, on testing the filtered liquid, the alkaloid reaction was not obtained, showing that the active principle was entirely dissolved from the whole seed by boiling water.
Statements have been advanced at various times to the effect that colchicia was precipitated along with the sediment that deposits from liquid colchicum preparations. The precipitated deposit was obtained from ten gallons of fluid extract of the seed, which had stood for six months. This sediment was carefully dried, washed with water containing about one-fifth its volume of alcohol until the washings passed tasteless, and then treated in the following manner: One-half of the washed residue was boiled with water acidulated with acetic acid, filtered, evaporated to dryness, treated with alcohol and water in the usual way, when, on adding the alkaloid test, not a trace of colchicia could be detected.
The balance of the residue was boiled in strong alcohol, filtered, the filtrate treated in the usual way; again no traces of colchicia could be observed.
The results of the different experiments lead to the following conclusions:
1st. That it is a waste of time and useless operation to powder colchicum seed, as the active principle can be wholly extracted by digesting them in the ordinary menstrua for a few hours, at a temperature of about 80°C.
2d. That alcohol stronger than dilute (sp. gr. .941) is unnecessary for any of the liquid preparations of colchicum seed, since the whole of the alkaloid can be extracted with that menstruum, or even with water.
3d. That the active principle is so soluble in the menstrua directed in the different officinal preparations, that it is impossible for it to be precipitated from such solutions, either as colchicia or in the modified condition of colchicein.