The method of obtaining the sumand b-ergocryptine

 

(57) Abstract:

Usage: ways to get drugs from plant material. The inventive product is the sum of alpha - and beta-ergocryptine, which are obtained by extraction of the crushed horns LPV ergocryptine strain dichloroethane, evaporation of the extracts for oil concentrate, the allocation of the amounts of ergot alkaloids and cleaning it on a dual sorbent is silica gel: activated angle. As eluent used chloroform. After evaporation of the eluates and recrystallization of the residue from benzene receive the sum of alpha - and beta-ergocryptine. Output - 73 - 78% of the content in raw materials. The method allows to simplify the technology, to reduce the process time and increase output (including production from mother solutions) from 60 to 73 - 78%.

The invention relates to pharmaceutical industry, and in particular to methods of obtaining drugs from plant material and concerns a method for obtaining the sum and ergocryptine source of the substance to obtain the drug "Amergin" with neurohormonal effects.

A method of obtaining the amount and ergocryptine, which crushed horns LPV ergocristine varicel), then dried raw material is treated with a suspension of magnesium oxide and extracted with xylene in the ratio of 1:5. From the organic phase alkaloids extract 2-5% solution of tartaric acid. Tartrate extract is alkalinized to pH 9-10 with ammonia and alkaloids extracted with chloroform. The chloroform extracts are evaporated to a small volume and poured into petroleum ether. Filter spin-off amount of alkaloids, which are divided into a column of silica gel L40/100 (mass ratio 1:30). and-ergocryptine elute with a mixture of chloroform-methanol (99:1), evaporated and crystallized from benzene. The output of the sum and ergocryptine is 60% [1] This method was adopted for the prototype.

The disadvantage of this method is a multistage process, its adaptability to manufacture, resulting in reduced yield of the desired product due to the losses in the individual stages and partial isomerization of the product, and the use of high-boiling and chemically aggressive xylene. In addition, the process involves the use of large amounts of organic solvents and the formation stages of solvent extraction of significant amounts of waste water polluting the environment.

The aim of the invention is to increase the yield of the target is cription, based on a new set of stages receiving the amount of alkaloids and purification, in which the extract obtained by treatment of the crushed horns LPV ergocryptine strain dichloroethane in an alkaline environment, evaporated to an oil concentrate, precipitate alkaloids by processing oil concentrate 10-fold volume of petroleum ether, filtered, washed, dried and purified the resulting amount of alkaloids on a column with dual sorbent: silica gel L5/40 activated carbon OC-A. as eluent used chloroform. The eluate concentrated to remove the solvent. The residue is recrystallized from benzene. The output 30 kg crushed horns LPV ergocryptine strain with the content amount and ergocryptine 0,3%).

For an additional amount of the target product recycle mother liquor, obtained after separation of the main mass of the product from benzene. The residue obtained after distillation of the benzene, treated with ethyl acetate, separating the precipitate, containing predominantly, and-ergocryptine, carry out the isomerization in a known manner [2] obtained the amount of alkaloids dissolved in a mixture of 25% ammonia-water chloroform (1:5:10), separate the chloroform layer, water is on a dual sorbent as well as described above, for the amount of alkaloids derived from raw materials. The product received is attached to the main.

Using dichloroethane instead of the high-boiling xylene allows evaporation of extracts without danger of destruction of the target product and receive a full solution composition the amount of alkaloids in oil (oil concentrate), whereas processing xylene extract the prototype tartaric acid inevitably leads to the loss of the target product. Dual sorbent allows you to combine the cleaning amount of alkaloids from alcaloide impurities (activated carbon), and separation of the alkaloids on silica gel. When this desired result is achieved only on a dual sorbent from the mass of sorbent and geometry kaloki (PL.1).

The results of the experiments are given in table.1, show that when cleaning the amount of alkaloids on a dual sorbent silica gel activated carbon products are obtained, corresponding to the requirements for the amount and ergocryptine [3] the Amount of coal is not significant, but its presence is necessary. Use for sorption any other sorbent, or silica gel and activated carbon alone does not allow you to plug isit output amount and ergocryptine from 65 to 73-78%

A new set of features of the proposed method (getting oil concentrate alkaloids, followed by separation of the target product with petroleum ether and the combined stages of purification and separation of alkaloids on a dual sorbent) will greatly simplify the technology of obtaining the sum and ergocryptine by reducing the number of stages (see table.2), which led to the reduction in the duration of the technological process from 70 to 44 h and decreasing solvent and sorbent (see tab.3).

Compliance with the proposed method the criterion of "novelty" is that the extraction Rozhkov LPV spend dichloroethane, and the resulting extract was evaporated to an oil concentrate and separate the amount of purified on a dual sorbent (silica gel-charcoal), as well as additional target product by processing uterine fluids.

Compliance with the proposed method the criterion of "inventive" is to use the dual sorbent for the purification of the amount of alkaloids containing and-ergocryptine that for these compounds in known sources not found.

The following are specific examples of implementation of the proposed method from raw materials aemula after separation of the finished product.

P R I m e R 1. Crushed horns LPV ergocryptine strain (content amount and ergocryptine 0,3%) in the amount of 30 kg loaded into the reactor, pour 170 l of dichloroethane and after stirring alkalinized with an aqueous solution of ammonia to a pH of 8. Extraction was carried out for 2 h at room temperature and constant stirring. Just spend 3 extraction. On the second and third extraction serves dichloroethane in the amount equal to the slit. The duration of the second and third extraction 1 including Third declaratively extract without treatment served on fresh raw next boot. The first and second dichlorethane extracts are evaporated at a temperature of 35 5aboutWith a residual pressure of 0.02 MPa to obtain an oil concentrate. Obtained oil concentrate was poured into 10 times its volume of petroleum ether (BP 70-100aboutC) suspension of alkaloids for weight deposition is kept in a refrigerated chamber at a temperature of 0 to 5aboutWith over 6 hours Worth of alkaloids was separated, washed with petroleum ether, dried for 12 hours at a temperature of 35 5aboutWith a residual pressure of 0.02 MPa. Get 180 g amount of alkaloids, which was dissolved in chloroform (1:1) and purified on a column with dual sorbent: 540 g of silica gel (nignt washed with 5 l of chloroform. Elution is carried out with help of vacuum. Get 5 liters of the eluate, which is evaporated in the same conditions as dichlorethane extracts, to remove solvent and the residue is recrystallized from 500 ml of benzene. For completeness, the highlight and ergocryptine the suspension is incubated at room temperature in the dark for 6 hours the Crystals amounts and ergocryptine was separated, washed with benzene (70 x 3 ml), dried under the same conditions, as the amount of alkaloids. Get 70 g amount and ergocryptine corresponding to the requirements of the product. The output of 65.1%

The mother liquor obtained after separation of the amount and ergocryptine and washing with benzene in the amount of 620 ml), evaporated in vacuum to remove the solvent. To the residue is poured 75 ml of ethyl acetate and leave for 5 days in the light at room temperature. Separate the precipitate, consisting mainly of and-ergocryptine, and after drying for 6 hours at room temperature is subjected to isomerization in known conditions: dissolved in 200 ml of methanol, add 2 ml of o-phosphoric acid, 6 ml of formamide, 100 ml of water. The resulting solution was concentrated to 40% of the original volume and left for 7 days at room temperature in the dark, periodically peremeshivanii layer. The aqueous layer was extracted with chloroform (75 x 2 ml), the combined chloroform extract with the bulk of the chloroform layer is dried over anhydrous sodium sulfate, evaporated to a small volume and purified on a column with dual sorbent in the same conditions as isolated from raw material the amount of alkaloids. After evaporation of the fractions containing and-ergokriptina, recrystallization from benzene, filtering and drying obtain 15.2 g-ergocryptine. The total output of the and-ergocryptine with regard to the processing of the benzene mother solutions is 85.2 g (content and ergocryptine 88,9% loss in mass on drying 15,6%), which corresponds to 78.2% of the content in raw materials.

P R I m m e R 2. Crushed horns LPV ergocryptine strain (content and ergocryptine 0,3%) in the amount of 30 kg load in the reactor, is poured into 170 l of dichloroethane and after stirring alkalinized with an aqueous solution of ammonia to a pH of 9. The entire process is conducted under the same conditions as in example 1. After purification on a dual sorbent and recrystallization from benzene obtain 71 g of the sum and ergocryptine (yield of 65.4%).

P R I m e R 3. Crushed horns LPV ergocryptine strain (content amount and ergocryptine 0,5%) in the amount of 30 kg load in the reactions which produce the amount of alkaloids from the oil concentrate. Get 210g amount of alkaloids, which was dissolved in chloroform (1: 1) and purified on a column with dual sorbent: 630 g of silica gel (lower layer) and 210 g of activated carbon (upper layer). The column diameter 190 mm After passing the basic solution of the alkaloids in chloroform, the sorbent was washed with 6 l of chloroform. Elution is carried out with help of vacuum. Get 6 liters of the eluate, which is evaporated in the same conditions as dichlorethane extracts, to remove the solvent. The residue is recrystallized from 700 ml of benzene under the same conditions as in example 1. Teaches 112 g amounts and ergocryptine (yield 65% ). Addition of the benzene mother liquor gain of 28.2 g amounts and ergocryptine (see example 1). The total yield amounts and ergocryptine with the content of the target substance 88,9% loss in weight on drying of 15.6% is 138,2 g or 73.2 per cent of the content in raw materials.

The use of the proposed method in comparison with the known provides the following benefits: simplification of the technological process, which are excluded from the production stage degreasing plant materials and drying, the stage of extraction of alkaloids from the xylene extracts tartaric acid and tartrate-outs on the Sabbath.

By simplifying technology and processing uterine benzene solution output amount and ergocryptine increased from 60 to 73-78% Reduction in total consumption of organic solvents and silica gel. The added value of the proposed method lies in the fact that the oil concentrate obtained by evaporation dichlorethane extracts, contains a whole range of different substances, which allows to obtain without significant additional costs such related ergocryptine substances as ergometrine ergotamine and the amount of lipid substances with biological activity.

The scheme receiving the amount and ergocryptine excludes formation in the production of wastewater, which has a positive impact on the environment and does not require the construction of sewage treatment plants.

1. A method of OBTAINING a SUM - AND - a-ERGOCRYPTINE by extraction of the crushed horns LPV ergocryptine strain with an organic solvent, evaporation of the extract and deposition of ergot alkaloids petroleum ether, filtration, washing, drying and cleaning of the amount of alkaloids, elution with chloroform and crystallization from benzene, characterized in that the extraction of lead dichloroethane with simultaneous formation and clearing amounts of ergot alkaloids on a dual sorbent silica gel activated carbon when the height of the layer of silica is not less than 50 mm, Royal solutions, obtained after crystallization from benzene, treated with ethyl acetate, separating the precipitate containing - and - ergocryptine, conduct the isomerization of o-phosphoric acid in water-methanol solution in the presence of formamide, the resulting amount of ergot alkaloids dissolved in a mixture of 25% ammonia water chloroform (1 5 10), separate the chloroform layer, the aqueous layer was twice extracted with chloroform, combined with the chloroform layer is dried, evaporated and purified on a dual sorbent in the same conditions.

 

Same patents:

FIELD: chemistry.

SUBSTANCE: ergot alkaloid is extracted from ergot with high yield and purity level using method including extraction of Claviceps purpurea, i.e. ergot, mix of solvents toluene/ethanol that leads to production of primary extract. The primary extract can be additionally treated within two stages of liquid-liquid extraction to provide alkaloid purification that gives purified toluene extract. Toluene extract can be additionally partially softened by stream, and crystalline product is produced by toluene crystallisation or mixture of toluene and aliphatic hydrocarbon.

EFFECT: development of method of ergot extraction with high yield and purity level.

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