Method for preparing diquertin

FIELD: medicine, natural compounds.

SUBSTANCE: larch wood is saturated with water and extraction with ethyl acetate is carried out. Prepared extract is treated with hot water and this process is combined with distilling off a solvent. Then water-insoluble resin impurities are separated and crude product is isolated by crystallization and recrystallized. Invention provides simplifying the process.

EFFECT: improved preparing method.

2 ex

 

The invention relates to medicine, namely to an improved process for the preparation of Divertida medical herbal remedies, with antioxidant, cardio, anti-inflammatory and hepatoprotective effects [FS 42-3855-99 "Tablet divertida 0.02 g"].

Decortin is a product containing more than 90% of bioflavonoid dihydroquercetin [FS 42-3854-99 "Decortin"] and released from Siberian larch wood (Larix sibirica Ledeb.) and Larix gmelinii ((Larix gmelinii (Rupr.) Rupr.).

Known methods of allocation of dihydroquercetin from the bark of Douglas fir [Pat. US No. 274919] and larch wood, based on aqueous extraction of plant materials [A.S. No. 351847 of the USSR, 1970; U.S. Pat. Of the Russian Federation No. 2000797, BI No. 37, 1993], as well as water-acetone extraction of wood [U.S. Pat. Of the Russian Federation No. 2038094, BI No. 18, 1995].

Analogue claimed is a method of allocation of dihydroquercetin by extraction pre-deresinated sawdust larch wood when heated organic solvent - ethyl acetate [U.S. Pat. Of the Russian Federation No. 2034559, BI No. 13, 1995], as well as the method of obtaining dihydroquercetin by extraction larch wood with ethyl acetate when heated, processing one stripped off extract gasoline or hexane to free him from resinous substances and crystallization DQC from aqueous solutions [U.S. Pat. Of the Russian Federation No. 2082425 from 27.06.97,]. ), The governmental lack of analogues is a huge consumption of two used organic solvents - hexane and ethyl acetate.

Closest to the claimed (prototype) is the method of receiving divertida by extraction larch wood with an organic solvent - ethyl acetate apparatus periodic actions with continuous circulation of the solvent, evaporation of the extract, dissolving the dried extract in hot water, filtering of resinous impurities and recrystallization of the product from hot water [U.S. Pat. Of the Russian Federation No. 2174403 from 10.02.98,].

The disadvantages of the prototype are:

- obtain the crude product with low content of dihydroquercetin - 37%, which implies a rather time-consuming cleaning of the drug to bring it to the Pharmacopoeia purity (more than 90% of the main product);

- the need to use expensive special filters for separating an aqueous solution of dihydroquercetin from resinous impurities.

The objective of the invention is a simplified method of obtaining divertida larch.

To solve this problem is proposed a fundamentally new way of making divertida from an extract of organic solvent, based on the combination of the distillation and solvent extraction using a binary system of immiscible liquids. This method allows one stage to separate decortin from resinous substances and other impurities from ethyl is letnogo extract with simultaneous regeneration of the solvent. The proposed method for the extraction of dihydroquercetin differs from existing high technological and economic indicators. The degree of extraction of dihydroquercetin reaches 90-95% of the content in the feedstock. Loss of solvent is not more than 1%. All recoverable extractive substances retain their native properties and have a high biological activity.

The problem is solved in that the crushed wood of a larch, pre-saturated with water, extracted with ethyl acetate, the extract is poured into the evaporating device, add water, an organic solvent evaporated, the aqueous layer was passed with him dihydroquercetin is separated from impurities resinous substances, cooled and precipitated upon cooling the product separated from the water. By recrystallization from hot water to get the product decortin that meets the requirements of the monograph.

As raw materials use crushed the butt part of the trunk of a larch, the most rich in extractive substances. The extraction is carried out in the apparatus of periodic action with continuous circulation of the extractant. Before extraction of the crushed raw material is saturated with water to change the physical properties of wood (increase in surface permeability, etc) to facilitate further deeper PR is the origin of the extractant in the microstructure of the wood which greatly facilitates the extraction of extractive substances from raw materials. In the process of removal of the solvent in the evaporation apparatus, water is added to obtain a binary mixture of immiscible liquids. After completion of the distillation, ethyl acetate, decortin, soluble in hot water, is transferred to the aqueous layer and water-insoluble impurities are easily separated from water. Upon cooling, the aqueous layer falls crude product containing 80-85% dihydroquercetin, for the final cleaning which requires only stage recrystallization from hot water.

The proposed method of obtaining divertida retains all the advantages of the prototype and has the following advantages:

preliminary saturation of the crushed material with water allows you to change the physical properties of wood (to increase specific surface area, permeability, etc. and reach the extraction of deeper penetration of the extractant in the microstructure of the wood, which greatly facilitates the extraction of extractive substances from raw materials, allows the extraction of a single stage, and to increase the degree of extraction of dihydroquercetin to 95% of the content in the feedstock.

use in the distillation of the solvent binary system of immiscible fluids ensures alignment process of distillation of the solvent from the process liquid extracts and and separation of water-insoluble impurities by a simple separation of the phases (liquid and solid), which allows to obtain the intermediate product with a basic substance content of 80-85% instead of 37%, as in the prototype). This greatly facilitates the subsequent bringing of the product to the pharmacopoeial parameters.

The proposed method was tested on an industrial plant with a capacity of 160 kg of divertida per month.

The method is illustrated by the following examples.

Example 1.

700 kg of crushed larch wood with a humidity of 40% is loaded into the extractor with a capacity of 4 m3. There also fill 300 litre hot water (temperature of 60-70°). After 30 min in the extractor serves 1700 l of ethyl acetate. The extraction was carried out under continuous circulation of the extractant and a temperature of 60-70°C for 3 hours. After the set time the extract is drained through the filter in the intermediate tank.

Received an ethyl acetate extract is fed to a distillation in the evaporation apparatus. In evaporating device previously placed 150 l of distilled water, heat the water to 70°and served continuously at a certain speed of an ethyl acetate extract. The distillation of ethyl acetate is carried out at a temperature of 76-78°C. After complete distillation of all of ethyl acetate in the apparatus is separated aqueous layer containing decortin, from water-insoluble resinous substances.

The aqueous layer was separated and cooled to 18°C. Fallen in ohlazhdeniya filtered off and get 6,74 kg of raw product, the content of dihydroquercetin which is 81.2 per cent.

The filtered crude product is passed on crystallization. The crude was dissolved in 70 liters of hot water (temperature of 95-98°C), stirred for 15-20 minutes and filtered. Then the aqueous solution is cooled to 18°and loose crystalline decortin separated by filtration. After recrystallization from hot water get 5,46 kg of dry product containing the main product was 92.3%. The output of divertida is 1.2% of the mass of absolutely dry wood.

Example 2.

In the conditions of example 1 is extracted with 700 kg of crushed larch wood with a moisture content of 35%.

Get 6,38 kg of raw product, the content of dihydroquercetin which is of 83.4%.

The filtered crude product is passed on crystallization. The crude was dissolved in 70 liters of hot water (temperature of 95-98°C), stirred for 15-20 minutes and filtered. Then the aqueous solution is cooled to 18°and loose crystalline decortin separated by filtration. After recrystallization from hot water get 5,86 kg of dry product containing the main product of 92.9%. The output of divertida is 1.3% of the mass of absolutely dry wood.

Quantitative analysis of the content of dihydroquercetin in raw materials, raw and final product is carried out by high performance liquid chromatography (who ASH) on the instrument with UV detector and column, filled with reversed phase (for example, Separon C18), the mobile phase - acetonitrile - 2% acetic acid (about 30-70.).

The method of receiving divertida by extraction of the crushed larch wood with ethyl acetate followed by treatment of the extract with hot water, distillation of the solvent, the separation of impurities and allocation of crude product, followed by recrystallization of the desired product, characterized in that the extraction is subjected to raw materials, pre-saturated with water, the Stripping solvent is combined with hot water, and then separating the water-insoluble resinous impurities.



 

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