RU2330677C1 - Method of dihydroquercetin production - Google Patents

Abstract

FIELD: medicine; pharmacology.

SUBSTANCE: wood of Siberian or Daurian larch is debarked, cleaved and dried at 40-50°C to residual moisture 23-27%. Dried wood is chopped, and soluble substances are extracted with 75-85% ethyl alcohol aqueous solution at temperature 45-50°C in ratio raw material:extracting agent 1:(7-10). Further extracting agent is distilled off, and sawdust is supplied to press for additional alcohol return. Then extract aqueous part is cooled to 20-25°C within 20-30 minutes for isolation of resinous impurity accompanying dihydroquercetin (DHQ). Deresined extract aqueous part is added with methyltertbutyl ether (MTBE) in ratio 1: (0.3-0.45), and DHQ is reextracted within 2-3 hours. Extract ether part is isolated separate from aqueous part through sedimentation within 2-2.5 hours and supplied to MTBE evaporation, while target product is crystallised of hot water. Invention enables to produce DHQ with yield 2.2-2.5% of bone-dry wood mass with grade 90-96%.

EFFECT: simplification of process and production of high-quality product.

4 cl, 2 ex

Description

The invention relates to the chemical and pharmaceutical industry and relates to the improvement of the method for producing dihydroquercetin (DHQ).

It is known that DHQ has antioxidant, angioprotective, regenerating, detoxifying, decongestant effects, has the ability to restore the elasticity of blood capillaries, prevents inflammatory processes, tumor formation, etc. Due to the widespread use of DHQ in the food, medical, and cosmetic industries, the task of developing improved methods for its preparation remains relevant.

There are various methods of processing wood and larch bark to obtain a wide range of biologically active products for the food industry and medicine (Babkin V.A., Ostroukhova L.A., Ivanova S.Z. and others. Products of deep chemical processing of larch biomass. Ros. Chem., 2004, vol. XLVIII, No. 3, pp. 62-69). The main active ingredient of the preparations obtained is dihydroquercetin (DHQ) - a flavonoid of natural origin with a wide spectrum of biological activity.

All known methods of chemical processing of coniferous wood can be divided into three groups:

1) methods involving the preparation of water-soluble products by processing the feedstock with aqueous solutions of electrolytes;

2) methods involving the preparation of non-water-soluble products — biologically active compounds, natural resinous substances — by treating raw materials with organic compounds (solvents);

3) methods involving the production of fiber and cellulose by processing raw materials with alkalis and acids.

However, existing methods for producing these products are characterized by a low coefficient of wood use (about 20-30%).

A known method, for example, is the isolation of DHQ from larch wood by extraction with water while heating, cooling, filtering and stirring the aqueous extract for 2 hours with a polyamide powder in a ratio of 1:10, filtering and drying the polyamide powder, extracting the DHQ with a polyamide powder with ethyl acetate and subsequent crystallizing it from hot water. (RF patent No. 2000797, class A61K 35/78, 1993).

The main disadvantage of this method is the low yield of the target product and the duration of the method.

A known method of producing DHQ by preliminary removal of water-soluble substances by washing sawdust of larch wood with water at ordinary temperature, followed by extraction of DHQ with a mixture of water-acetone (1: 4) at ordinary temperature. Precipitated after acetone distillation from the aqueous part of the extract, the DQW precipitate was recrystallized from hot water. The purity of the obtained DHQ is 95-97%, the yield is 1.75-2.0% by weight of absolutely dry wood (a.s.d.) (RF Patent N 2038094, class A61K 35/78, publ. 06/27/95) .

The disadvantages of this method are the length of the process due to the stage of preliminary washing of sawdust with water, a decrease in the yield of DHQ due to losses during washing of sawdust with water, as well as the huge consumption of an expensive extractant - acetone, which, due to its unlimited solubility in water, is difficult to regenerate.

A known method of producing dihydroquercetin, including extraction of crushed coniferous wood by heating, filtering the extract, evaporating it, extracting the target product, crystallizing it from hot water and drying, characterized in that larch or Douglass fir is used as coniferous wood, extraction is carried out with ethyl acetate within 1-5 hours at a ratio of crushed larch wood or douglass fir and ethyl acetate 1: (5-7), and the target product is extracted from the stripped off extract stvlyayut hexane or gasoline at a ratio of respectively 1: (8-20), the desired product extraction process is carried out at a temperature of 18-24 ° C for 15-40 minutes and stirring, after which hexane or benzene is distilled off. The purity of the target product is 94-96%, the yield of dihydroquercetin is 0.9-1.0% by weight of absolutely dry wood (RF Patent No. 2082425, class A61K 35/78, publ. 06/27/1997).

The disadvantages of this method are the high consumption of organic reagents and low yield of the target product.

A known method of producing DHQ from crushed larch wood, including preliminary impregnation with the last water (at a temperature of 25-40 ° C), extraction with ethyl acetate (ratio of raw materials: extractant 1: 4), evaporation of the extract and processing with gasoline (or hexane) without heating to remove the resin . The tarless extract is treated with hot water (temperature 95-98 ° C), filtered from impurities. Upon cooling, crystals of DHQ precipitate from the aqueous solution. The purity of the obtained product is 90-95%, the yield of DHQ from the mass of absolutely dry wood is 1% (RF Patent No. 2158598, class A61K 35/78, publ. 10.11.2000).

The main disadvantages of this method are the high consumption of organic extractants (gasoline and ethyl acetate), and, accordingly, the high energy consumption for their evaporation and heating during extraction, as well as the low yield of the target product.

The closest to the claimed method of the prototype is a method for producing dihydroquercetin, which includes the following stages (RF Patent No. 2034559, A61K 35/78, publ. 05/10/1995).

The crushed and dried larch wood (relative humidity 7%) is poured with n-hexane or gasoline and refluxed for 1 hour. Then the solvent is drained, and the resin-free sawdust is poured with ethyl acetate, heated to boiling point (77 ° C) and refluxed for one hour. The hot extract is filtered off from sawdust, cooled and evaporated. The dry extract is poured with hot water (ratio 1:10, 80 ° C) and dihydroquercetin is isolated by crystallization from hot water. The yield of dihydroquercetin is 0.81-0.91 by weight of absolutely dry wood, the purity of the target product is 92-96%.

The disadvantages of this method are the duration of the process, as well as the low yield of the target product.

An object of the invention is to increase the yield of the target product while maintaining its high quality.

The technical task is achieved by the proposed method, which consists in the following.

Siberian or Daurian larch wood is cleaned of bark, chopped and dried at 40-50 ° C to a residual moisture content of 23-27%. The dried wood is ground and loaded into the extractor. Soluble substances are extracted from the crushed wood of larch with an aqueous solution of ethyl alcohol with an organic content of at least 75%, mainly 75-85% (an azeotropic mixture of ethyl alcohol-water), at a temperature of 45-50 ° C at a ratio of raw material: extractant 1: (7 -10). Next, the extractant is distilled off, and sawdust with the rest of the extractant is fed to the press for additional alcohol recovery. Then the aqueous part of the extract is cooled to 20-25 ° C for 20-30 minutes to remove the accompanying DHQ gummy impurities.

Methyltrebutyl ether (MTBE) was added to the demineralized aqueous part of the extract (concentrate) in a ratio of 1: (0.3-0.45) and DCB was reextracted at a temperature of 34-36 ° С in vacuum for 2-3 hours. The ether part of the extract is separated from the water part by settling for 2-2.5 hours and served for evaporation. After evaporation of the ether fraction, distilled water is added to the dry residue, the aqueous solution containing DHQ is heated to 50 ° C and the latter is crystallized from hot water.

The proposed method allows to obtain DHQ with a yield of 2.2-2.5% by weight of absolutely dry wood with a purity of 90-96%. The chemical composition of DHQ is proved by elemental analysis on C, H, O and high performance liquid chromatography by HPLC.

The defining hallmarks of the proposed method, compared with the prototype, are:

1. The extraction of raw materials is carried out with 75-85% ethyl alcohol at a temperature of 45-50 ° C at a ratio of raw materials: extractant equal to 1: (7-10), which can significantly simplify the process technology, exclude from the process the stage of preliminary resin reduction of crushed wood with non-polar hydrocarbons (n-hexane or gasoline), to make the process economical and more profitable, since the temperature of wood processing is reduced to 45-50 ° C.

2. The resulting aqueous portion of the extract (after separation of the extractant) is cooled for 20-30 minutes to 20-25 ° C for the deposition of resinous impurities, which improves the purity of the target product.

3. From the tarless extract, the DHQ is re-extracted with methyl tert-butyl ether at a ratio of 1: (0.3-0.45) for 2-3 hours, which allows additional purification of the target product from impurities of resins and oils.

Methyl tert-butyl ether has valuable technological qualities and is cheap. It has a boiling point favorable to the process / 52 ° C /, almost does not dissolve water and other polar substances, and very well dissolves organic compounds of medium polarity, which include DHQ. It is very important that methyltrebutyl ether, in contrast to the ether solvents known for this process, such as diethyl ether, dioxane, tetrahydrofuran, poorly forms peroxides and is therefore more preferred in terms of explosion safety.

The invention is illustrated by the following examples of specific performance of the method.

Example 1

Siberian larch wood is cleaned of bark, chopped and dried at 50 ° C to a residual moisture content of 23%. The dried wood is crushed first on an MPN-20 chipper to the size of technological chips, then to particles 1 × 0.1 × 1 mm in size on a knife crusher and loaded into an extractor with a working volume of 6 cubic meters.

450 kg of crushed larch wood is poured into 3465 liters of a 75% aqueous solution of ethyl alcohol (raw material – extractant ratio 1:10) and extraction is carried out at a temperature of 50 ° C with constant stirring for 3 hours. Next, the aqueous-alcoholic extract is fed to a vacuum evaporator, and sawdust by a screw conveyor, with the remainder of the extract, is fed to an E8MPSh-01 screw press, where the extract is additionally pressed, which is also fed for evaporation in a vacuum evaporator. The remaining mass of wood is fed to a PG-310 granulator to obtain fuel pallets.

The distilled alcohol is returned to the technological cycle, and the aqueous part of the extract (concentrate) is poured into a container with a “jacket”, cooled for 30 minutes to 20 ° C, and the resin is deposited at the bottom of the container, which is removed manually with a spatula.

The tarless concentrate (220 liters) is pumped into a container for ether reextraction, 100 liters of methyl tert-butyl ether are added and the DHQ is re-extracted in 0.2 MPa vacuum with stirring (pumping in a closed circle) at 36 ° C for 2 hours. Next, the ether part of the extract is separated from the water part by settling for 2.5 hours, the water is drained, and the ether fraction containing DHQ (95 liters) is fed for evaporation.

After evaporation of the ether fraction, distilled water (190 liters) is added to the dry residue, the aqueous solution containing DHQ is heated to 50 ° C and poured into a container where the target product crystallizes when water is cooled from 50 to 18 ° C for 2 hours. After that, the DHQ is filtered on Buchner funnels on a paper filter and then the target product with a humidity of 45% is dried in cabinets at a temperature of 50 ° to a residual moisture content of 7%.

The yield of DHQ was 2.2% by weight of absolutely dry wood with a purity of 94%.

Example 2

Daurian larch wood is cleaned of bark, chopped and dried at 40 ° C to a residual moisture content of 27%. The dried wood is crushed first on an MPN-20 chipper to the size of technological chips, then to particles 1 × 0.1 × 1 mm in size on a knife crusher and loaded into an extractor. From 450 kg of crushed larch wood, soluble substances are extracted with an 85% aqueous solution of ethyl alcohol at a temperature of 45 ° C with a raw material - extractant ratio of 1: 7 (2300 L), with constant stirring for 2 hours. At the end of the extraction, the aqueous-alcoholic extract is pumped out with a vacuum pump and fed to a vacuum evaporator for distilling off alcohol, and sawdust with the remainder of the extract is fed to a press. The alcohol obtained as a result of distillation is returned to the technological cycle, and the aqueous concentrate is poured into a container with a “jacket”, cooled to 20 ° C for 20 minutes, and the resin is deposited at the bottom of the container, which is removed manually with a spatula.

In 300 L of tarless concentrate, 100 L of methyl tertbutyl ether is added and the DHQ is reextracted with stirring at 34 ° C in 0.2 MPa vacuum for 3 hours, after which MTBE is separated from the water by settling for 2 hours, the water is drained, and the ether fraction containing DHQ (95 liters) is fed for evaporation.

After evaporation of the ether fraction, distilled water (240 liters) is added to the dry residue, the aqueous solution containing DHQ is heated to 50 ° C and poured into a container where the target product crystallizes upon cooling water from 50 to 18 ° C for 2 hours. After that, the DHQ is filtered off and then the target product with a moisture content of 55% is dried in cabinets at a temperature of 50 ° to a residual moisture content of 8%.

The yield of DHQ was 2.5% by weight of absolutely dry wood with a purity of 96%.

Using the proposed method will allow:

- increase the yield of DHQ to 2.2-2.5% while maintaining a high degree of purity of the target product;

- to simplify the method by eliminating from the technology a long and laborious stage of preliminary demineralization of the feedstock;

- increase the environmental safety of the method by eliminating fire hazardous, toxic solvents from the process: ethyl acetate, n-hexane, benzene;

- reduce the cost and improve the quality of the target product, since the latter is obtained in the native form, having an undisturbed natural structure, because the process proceeds at low temperatures, in contrast to high-temperature analogues, with the inevitable decay of the structure and losses of up to 70% of the final product.

The proposed method allows to obtain DKV with a high yield and a high degree of purity, significantly simplify the process technology, reduce the process time and provide the ability to process large (hundreds of tons) of raw materials.

Claims (4)

1. The method of producing dihydroquercetin (DHQ), including the extraction of the latter from crushed larch wood with an organic solvent by heating, distillation of the extractant, extraction of the target product from the aqueous part of the extract, its crystallization from hot water and drying, characterized in that the extraction is carried out with an aqueous solution of ethyl alcohol with an organic content of 75-85% at a temperature of 45-50 ° C for 2-3 hours with a ratio of crushed wood and extractant equal to 1: (7-10) obtained after distillation of alcohol aqueous ext the ract is cooled to 20-25 ° C for 20-30 min to remove gummy impurities, the DHA is re-extracted with DCT methyl tert-butyl ether at a ratio of 1: (0.3-0.45) for 2-3 hours, followed by separation of the ether parts of the extract and evaporation of methyl tert-butyl ether. 2. The method according to claim 1, characterized in that the larch wood is used with a moisture content of not more than 27%. 3. The method according to claim 1, characterized in that the extraction of DHQ with methyl tert-butyl ether is carried out at a temperature of 34-36 ° C in a vacuum of 0.2 MPa. 4. The method according to claim 1, characterized in that the ether part of the extract containing dihydroquercetin is separated by settling for 2-2.5 hours