CS208911B1 - Isolation method of alcaloids from ergot - Google Patents

Description

(54) A process for the isolation of alkaloids from ergot

SUMMARY OF THE INVENTION The present invention provides a process for the isolation of a crude sum of polypeptide-type alkaloids and ergometrine from ergot, which makes it possible to obtain alkaloids in a high yield and a high degree of purity.

Isolation of biologically active ergot constituents of the polypeptide type, referred to as water-insoluble alkaloids, and ergometers, referred to as water-soluble alkaloids, has been the subject of a number of publications and patents. These works are mostly aimed at obtaining more or less complicated crude mixtures of said alkaloids, which are then, in the next working stage, processed into individual pure alkaloids, respectively. alkaloid. Of course, the most advantageous method of ergot processing is one which, without time-consuming and materially defatting of the drug, allows it to obtain, in maximum yields, all therapeutically valuable alkaloids, in the first stage of work, in the form of the purest raw summaries, respectively. crude alkaloids. These requirements for isolating alkaloids from ergot are necessarily associated with the use of an industrially readily accessible extracting agent or solvent mixture in which the ergot alkaloids are as well soluble as possible and in which the non-alkaloid drug substances are at the same time as soluble as possible.

The most commonly used extraction agents include, for example, ether, methanol, acetone, chloroform, benzene, and others. The solvents have either the ability to selectively remove alkaloids from ergot, but the solubility of alkaloids in them is relatively low (e.g. ether), while the other ratios are reversed (e.g. methanol, acetone), which is also in terms of ergot processing its alkaloids are disadvantageous. Finally, some of them must also be rejected for health reasons (benzene) or high prices (chloroform). The milled drug prior to extraction is most often defatted, e.g., with petroleum ether, and then treated by alkalization, e.g., with caustic soda, sodium carbonate, or by the addition of an acid, such as tartaric acid.

Dle čsl. No. 85995, a process for the isolation of ergot alkaloids in the form of a crude alkaloid summary is characterized in that an ether mixture with polar solvents, in particular alcohols, is used alone or in combination to extract the defatted or non-defatted, basified ergot. a well-known, separately performed extraction with ether. Nevýho208911

208 911 for use with, for example, ether-ethanol mixtures for drug extraction is that the crude alcohol-alcohol extract obtained from the crude polypeptide-type alkaloid is highly contaminated with ballast substances.

It is an object of the present invention to provide an ergot extraction process which allows to obtain, in an economically satisfactory yield, a crude sum of polypeptide-type alkaloids in a high degree of purity, as well as a water-soluble ergometrine in a high yield.

The process according to the invention consists in extracting the defatted or non-defatted, ground ergot with an ethanol-ethanol-saturated water mixture, preferably providing the water required to saturate the total amount of the ether-ethanol mixture used into the extracted drug, both water and solution. or a suspension of inorganic alkali in the same volume of water, or a suspension of zinc oxide in the same volume of water, after which the alkaloids are taken from the extracts into an aqueous solution of an organic acid and the alkaloids released are eventually freed. and the aqueous mother liquor is worked up in a known manner into a further proportion of water-insoluble alkaloids and ergometrine.

The use of ether mixtures with 5-25% by volume of ethanol, preferably 10% by volume of ethanol saturated with water allows both alkaloid bases (when using an aqueous solution or suspension of inorganic alkalis) and their salts or salts to be dissolved. mixtures of salts with bases (using water alone). The use of zinc oxide in the said extraction is associated with the containment of a large portion of the ballast substances in the drug, thus making it possible to obtain a particularly high percentage of water-insoluble alkaloids.

With respect to the quality of the crude polypeptide-type alkaloid pool, the process of the invention allows, for example, from a high-volume ergotamine-type ergot a pool of water-insoluble alkaloids which is 80-93% (calculated as ergotamine).

The use of water in the extraction of the drug by the method of the invention is also essential for yielding a crude sum of polypeptide-type alkaloids. Thus, for example, in the same manner of extracting the same, ground ergotamine ergot-type ergot with a mixture of ether with 10% ethanol when water alone and an aqueous sodium bicarbonate solution were used, the yield was 69% without water or water. only in the presence of water contained in the drug (6%), on the other hand, the yield was only 47% and

Claims (1)

SUBJECT A process for the isolation of alkaloids from ergot, characterized in that the ground, defatted or non-defatted ergot is extracted with a water-saturated mixture of ether of zinc oxide slurry in water (20% by weight per water used) yielding about 84%. Depending on the number of extractions, event. at the time of the continuous extraction and the amount of solvent mixture used, the yield according to the invention can be easily achieved economically fully satisfactory. The use of mixtures of ether with ethanol saturated with water also allows the recovery of ergometrine from the drug in high yield. Ergometrine can be obtained, along with another small proportion of polypeptide-type alkaloids, from aqueous mother liquors after separation of the major portion of the latter alkaloids, by some known method, for example according to W. A. Jacobs and L. C. Craig (Science 82, 16 (1935)). Exemplary embodiment A 1.0 kg ground, non-defatted ergotamine-type ergot containing about 6% water and 4.7 g alkaloids (calculated on ergotamine) was charged with a suspension of 50 g zinc oxide in 250 ml water. The mixture was kneaded vigorously and allowed to stand at room temperature for 2 hours. The mixture was then transferred to a separatory funnel, poured over 2,500 mL of ether / ethanol (9: 1 by volume) and after 9 h standing the extract was drained. For the next four extractions, 2,000 ml of an ether / ethanol mixture of the same composition as above were used, each extraction lasting 9 hours. From the combined extracts, the alkaloids were taken up in a 1% aqueous tartaric acid solution (shaken until aqueous). the ergot alkaloids with the KellerKilian reagent) combined aqueous acidic extracts were basified with conc. aqueous ammonia and the precipitated bases were aspirated after about 3 hours of standing, washed with a little cold water and air dried at room temperature, avoiding direct light. 4.03 g of an almost colorless ergotamine pool were obtained which, by drying at 100 ° C / 266.6 Pa, lost weight by 3.3%. The dried sum is 85-90% (calculated on ergotamine). A further increase in the alkaloid content of the pool can be achieved by defatting it with petroleum ether, e.g., 1 hour by mixing the pool with about twenty times the weight of petroleum ether and washing the aspirated product with about three times the same solvent. The aqueous mother liquor of the water-insoluble alkaloids, obtained by aspiration and washing of the precipitated bases, was treated to a further fraction of polypeptide-type alkaloids and ergometrine, for example, as described in section e. No. 85995. Altogether approximately 84% of the alkaloids found in the drug were removed from the drug by extraction. 5 to 25% by volume of ethanol, wherein either water alone or an aqueous solution or an aqueous suspension of inorganic alkali or an aqueous suspension of zinc oxide, preferably pre-homogenized with extracted ergot, are used to saturate the extraction mixture; and from this 208 911 of the solution is alkalized to liberate the alkaloid bases, which after isolation or separation of the alkaloids. defatting, whereupon the remaining mother liquor is processed in a known manner to further water-insoluble alkaloids and ergometrine.