The allocation method chenodesoxycholic acid fractions of lipids, cholesterol and fractions of fatty acids

 

(57) Abstract:

Usage: as a treatment for gallstones without surgery. The inventive product is chenodeoxycholic acid (CDCA) + fraction of lipids, cholesterol and the fraction of fatty acids. Exit 71 - 76% (cholesterol). Reagent 1: gallbladder birds. Reagent 2: alkali. Reagent 3: a mixture of ethyl alcohol and toluene in a ratio of 0.25 : 1. After separation of the fractions of lipids from the extract to produce cholesterol. The hydrolysate is treated with mineral acid to pH 1 to 3 and add bipolar extractant preferably ethanol, petroleum ether, hexane to allocate fractions of fatty acids. The translation of the low-melting CDCA with so pl. 120 - 128C in high-melting with so pl. 160 - 164C is carried out in a weak alkaline solution by acidification with mineral acid to pH 4 to 4.5 by extracting it with an organic solvent, concentrating the extract and adding to the residue malopolyarnoi solvent from the extract solution at 6 to 2C, the precipitation CDCA with so pl. 140 - 145C boil in an organic solvent with so Kip. 60 to 140C. 4 h.p. f-crystals.

The invention relates to the chemistry of steroids and specifically relates to a method of separately allocating chenadec.

Chenodesoxycholic acid (3 , 7-dihydroxy-5-Holan-24-OIC acid, abbreviated CDCA) of the formula I

< / BR>
Has the ability to dissolve cholesterol gallstones and is used for the treatment of gallstone disease, especially in those cases where surgical intervention is associated with increased risk. In medical practice known as drug Hinopak (Germany), Deuel (Italy), Henkel (Yugoslavia), Chenodiol (USA) [1]

The fraction of lipids is a mixture of lipids, in which the main component (75%) is cholesterol.

Cholesterol is used in the medical industry as a feedstock for the production of the hormonal drugs, as well as in the cosmetic industry as supplements [2]

The fraction of fatty acids used in soap-making as a raw material in the cosmetic industry as fat additives in the manufacture of cosmetics [3]

In the literature it is not described how the selection of the gallbladder birds as fractions of lipids, and the fraction of fatty acids.

Known methods of excretion of bile acids, including the CDCA [1] of bile birds.

These methods differ in the source of bile, which is dried whether different labour-intensive methods of drying, such as freezing, lyophilization, spray or drum drying.

One such method of selection CDCA, where the quality of raw materials used raw (fresh) chicken bile extracted from the gall bladders of birds, is the following:

raw chicken bile (raw bird bile contains bile acids, among which the largest percentage falls on the CDCA (80-85%) and cholic acid ( 10%), and also contains lithocholic acid and other acids, in addition, lipids, fatty acids, pigments extracted with ethanol;

the extract obtained was purified from pigments liver, passing through a column of alumina;

the eluate containing conjugates (bile acid in bile as conjugates with one of the amino acids: taurine or glycine) bile acids, alkali hydrolyzing (24 h);

the obtained hydrolysate containing CDCA (1), acidified with hydrochloric acid (pH 1-3).

Technical acid 1 (phase precipitate) was dissolved in ethanol-water mixture (volume ratio 1:1), add petroleum ether (mixture: ether 1:1);

after separation of 2 layers: petroleum and water-alcohol, the latter is evaporated to dryness;

the residue is dissolved in ethanol and the resulting solution CFCS is re caustic soda and the solution acidified with hydrochloric acid;

precipitation CDCA (1), cleared of lipids, fatty acids and other impurities.

From 1 l of crude bile get 40-50 grams ( 4-5%) net CDCA (1).

Quality not specified [4]

The closest in technical essence and the achieved result similar to the proposed method, i.e., the prototype, is the method of allocation of CDCA (1) in the form of a pure substance from a raw (fresh) bile birds [5]

This method consists in the fact that crude bile (separated from the gallbladder birds) dehydrate; the resulting dry bile is extracted with an organic solvent (e.g. methanol); extract containing conjugates of bile acids, atrificial (treated with mineral acid); obtained in the form of ester conjugates of bile acids is separated from the lipids, fatty acids, pigments and other impurities by treating them with an aqueous-organic mixture (chloroform-water) with subsequent separation of the two phases: organic (impurities) and water-organic (ether conjugates of bile acids) and parcoy last dry; ester conjugates of bile acids (dry residue) hydrolyzing in an aqueous solution of sodium hydroxide; the resulting sodium salt of the free bile acids is treated with mineral acid (pH 2-1); received ieeestore a 10% aqueous solution of ammonia by boiling and add a 10% aqueous solution of barium chloride (dropwise);

the mixture is cooled, check for completeness of precipitation of barium chloride salts, filtered, dried (60aboutWith a vacuum, 48 h);

the resulting barium salts of bile acids, mainly barium salt CDCA (hereinafter mean only CDCA, crystalline precipitate), washed with methanol, dried (60aboutC, vacuum);

add ethyl acetate and hydrochloric acid;

an ethyl acetate solution of CDCA (1) washed with water, dried (sodium sulfate), evaporated to dryness;

the resulting acid 1 (dry residue) re-purified via barium salt (the residue is dissolved in methanol, add 25% ammonia solution and 10% aqueous solution of barium chloride by boiling; the mixture is cooled, check for completeness of precipitation of the barium salt, filtered, the precipitate washed, dried (60aboutWith a vacuum, 48 h); to the resulting barium salt CDCA (crystalline residue are added ethyl acetate, and then hydrochloric acid; an ethyl acetate solution CDCA washed with water, dried (sodium sulfate), evaporated to 1/3 volume; in concentrate CDCA add hexane with stirring, and incubated for 12 h at 4aboutC).

So, get clean CDCA with the release of 4-6,4% (considering the weight of the original crude bile) in powder form with so pl. 140-142aboutC.

who cannot be considered reliable, since this patent [5] does not specify the content of pure bile in the feedstock (crude bile).

As for the quality acid 1, it is known [6] get 1 stable quality in a patent [5] it is impossible.

The main disadvantages of the prototype method [5] are:

the complexity of the raw materials (bile) and prepare it for the process of selection of the target products (CDCA, fraction lipid fraction of fatty acids).

Time-consuming operation Department the most gallbladder bile, which must be performed very carefully and precisely, without perezi other tissues, the presence of which complicates the selection of target products in the prototype.

Also consuming the next operation squeezing out bubbles the bile that, as a rule, fully to make this operation difficult and this leads to loss of bile.

In this way [5] it is acceptable to use only their bile and dried soon after squeezing out the bubbles. The drying operation, which requires large amounts of manual labor, expensive equipment and energy costs.

Preparation of bile deposited to produce impractical Taka are the need for allocation of bile conjugates of bile acids in the form of a methanol extract; obtaining conjugates of bile acids in the form of esters, the allocation fractions of lipids and fatty acids in the mixture, which is not utilized and discharged into the drainage system.

As seen above, the complexity of obtaining and preparation of raw materials (bile), the impossibility of its full use, as well as others mentioned disadvantages of the prototype method complicate the creation of a national industrial way separate allocation CDCA 1, the fraction of lipids (cholesterol) and fractions of fatty acids.

The purpose of the invention to simplify the process and better use of animal source of valuable raw materials (bile).

This goal is achieved by the proposed method, a separate allocation fractions of lipids, including cholesterol, fractions of fatty acids and CDCA (1), namely, that the gall bladders of birds (prorezyami other tissues), containing conjugates of bile acids and lipids, fatty acids, is subjected to alkaline hydrolysis at 94-97aboutWITH:

the resulting hydrolyzate (a mixture of lipids, salts of an alkali metal fatty and bile acids) extracted with a lower alcohol and monopolarly solvent, taken up in a volume ratio (0,2-0,25):1 respectively otorgada mainly cholesterol) is separated and, after purification and evaporation, distinguish by the crystallization of cholesterol; remaining after the extraction of the hydrolysate containing alkali metal salts of bile and fatty acids, mineral process (e.g., hydrochloric) acid to pH 1-3 and allocate the fraction of fatty acids by extraction of its lower alcohol and monopolarly solvent taken in a volumetric ratio, respectively (0,15-0,25): 1 relative to the aqueous alkali used for hydrolysis of the gallbladder; the resulting extract fraction of fatty acids is separated and evaporated to dryness, and the remaining after the extraction of the hydrolysate containing bile acids, including CDCA (1), handle lower alcohol and monopolarly solvent taken in a volumetric ratio, respectively, as (0.4 to 0.5):1 relative to the aqueous alkali used for the alkaline hydrolysis of bubbles; the resulting extract fraction of bile acids, mainly CDCA (1) is treated with a weak solution of aqueous alkali, followed by the separation of the resulting aqueous phase containing CDCA (1), and its treatment of the mineral acid, obtained in the form of sediment CDCA purified from holeva acid by dissolving the precipitate in a weak alkali solution, followed by precipitation of mineral acid on the in solvent, having a boiling point within 65-140aboutC.

Description allocated by the present method products.

The fraction of lipids obtained as a crystalline precipitate, yellowish-brown with the release of 0.16-0.23% of the feedstock. Is a mixture of lipids, where the main component (75%) is cholesterol.

Cholesterol is manufactured in the form of white crystalline powder, so pl. 145-149aboutWith that meets all the requirements of the Pharmacopoeia X.

Output pharmacopoeial cholesterol is 60-65% by weight of the lipid fraction or 0.1-0.2% of the mass of the initial gallbladder.

The fraction of fatty acids, consisting of acids having so pl. 35-40about(Low-melting) and 60-70about(High-melting) are obtained in the form of a waxy mass, colored from yellow to light brown in color, with the release of 7-9,7% by weight of the original gallbladder.

CDCA (1) receive in three crystalline forms, differing in melting point.

Low-melting form crystals with so pl. 119aboutC;

Low-melting form of needle crystals, so pl. 138-140aboutC;

High-melting form lamellar crystals, so pl. 164 + 4aboutC (lit.data (7) so pl. 168about

The content of the basic substance 95-97% holeva acid (impurity) is not more than 2%

Specific rotation 12about+2 /a 1% solution of alcohol.

In the present method as a lower alcohol is used, for example methanol, isopropyl alcohol, preferably ethanol.

As malopolyarnoi solvent used, for example, xylene, toluene, petroleum ether, gasoline, hexane.

As the alkali used for hydrolysis gallbladder, use 9-11% aqueous solution of caustic alkali. When the alkali concentration <9 or >11% of the observed increase in time of hydrolysis or resinification product.

The hydrolysis is carried out at 94-97aboutWith, because at temperatures above 97aboutWith observed foaming of the reaction mixture and at a temperature below 94aboutWith slowing the process of hydrolysis gallbladder.

As a weak aqueous alkali solution used for cleansing stage 1 from holeva acid, use a 1-5% aqueous solution of caustic alkali (sodium hydroxide or potassium).

Distinctive features of the proposed method:

use as feedstock directly gallbladder with bile and prorezyami other tissues (in the prototype used for changing the sequence of the stages of purification and the allocation of CDCA (1) (prototype conjugates of bile acids is first allocated, transferred to the ethers and the last clear of lipids, fatty acids and other impurities, while the mixture is not shared and is not disposed, and the purified esters again transferred to the conjugates of bile acids and subjected to hydrolysis; in the present method, the conjugates of bile acids directly subjected to hydrolysis without preliminary allocation);

the use of manual extraction for separation of the lipid fraction, the fraction of fatty acids and CDCA (1) using bipolar extractant;

use as bipolar extractant mixture malopolyarnoi solvent and a lower alcohol, taken in a certain ratio at the stage of allocation fraction lipid fraction of fatty acids and stage separation and purification 1;

cleaning requirements CDCA from holeva acid from the alkaline solution.

The set of distinctive features in the claimed method creates a number of positive effects.

Use directly gallbladder with bile and prorezyami other tissues with the aim of identifying CDCA, lipids and fatty acids offered for the first time. This allows you to solve a number of problems that occur in the use and storage of crude bile.

extraction of bile from the gallbladder.

This operation is time-consuming, it is inevitable, significant losses of raw materials, so as to press full of bile impossible.

In addition, when pressed into the bile may hit residues gallbladder, fat and other connective tissue, which does not allow the prototype to conduct a satisfactory cleaning CDCA from impurities, eliminating the need for costly drying process wrung bile, because the storage begin the process of decay (in the present method it is possible to use gall bladders, frozen (in the form of pellets) that, as necessary, allows them to dispense).

The possibility of direct hydrolysis of conjugates of bile acids compared with the prototype allowed us to greatly simplify the process, namely, to exclude a number of allocations conjugates of bile acids in the form of alcohol solution and their transformation into the corresponding ethers; branch esters of water-organic mixture from the lipid fraction, the fraction of fatty acids, and pigments and other impurities, which leads to the formation of unusable waste water; the transformation of these esters in sodium salt.

Sequential extraction fractions of lipids, fatty Ki is islote (CDCA) from the acidic environment.

First found conditions selective separation CDCA, lipids and fatty acids. These conditions are determined experimentally.

In table. 1 shows the limits of the found ratios of the aqueous phase, alcohol and malopolyarnoi solvent.

The limits found ratios of the aqueous phase, alcohol and malopolyarnoi solvent are necessary and sufficient for the selective separation of these products.

Outside of these correlations is not enough to divide and allocate these substances.

So, in case of separation of lipids by reducing the amount of alcohol, there is no separation of the aqueous and organic layers due to the formation of the emulsion, in the allocation of fatty acids observed incomplete removal, and when the allocation of CDCA (1) there is no extract 1, it falls in the aqueous phase in the form of resin.

When the quantity of alcohol in bipolar extractant in case of separation of lipids get intensely colored pigments solutions, i.e., the product get contaminated; allocation of fatty acids extracted along with them and partly CDCA, which leads to the loss of its output; selection CDCA excess alcohol leads to incomplete cleaning to alsowhat feedstock, because it enables you to separately receive three target product: CDCA (1), cholesterol, which is the main product of the fraction of lipids, and the fraction of fatty acids.

All these products are obtained with high yields and they are, as mentioned raw material in several industries.

First found cleaning requirements CDCA inseparable from impurities holeva acid.

In the search process of deposition conditions CDCA and holeva acid on pure samples observed that CDCA begins to precipitate from the alkaline solution in the range of pH of 7.2 to 6.0, preferably from 6.4 to 6.2), and cholic acid at pH < 5,9 that for the first time allowed almost full so we split them.

On the basis of the proposed method can be created domestic industrial production CDCA particularly important medicinal substance, and at the same time to get together with him and other important primary sources for a number of sectors (medicine, soap making, cosmetics) cholesterol, fatty acids.

P R I m e R 1 (preferred terms). To 1603,3 g thawed gallbladder with prorezyami other tissues (meets the requirements of THE 10.18.11.010-90) obtained from hens and broiler chickens, with humidity 71,4% of the etoy, to the concentration of the sodium hydroxide solution in the reaction mass was 10% (using 9-11% aqueous solution of alkali does not affect the result of hydrolysis). Total volume of 10% sodium hydroxide solution must be in the amount of 1:4 by weight of dry residue gallbladder and is 1834 ml.

The reaction mass is heated to 94-97aboutTo conduct hydrolysis during 26-27 h at the same temperature.

The resulting hydrolyzate is cooled to 35-45aboutWith, poured 458,5 ml of ethyl alcohol (25% by volume of a 10% aqueous solution of caustic soda or 12.5% alcohol content in the reaction mass) and 1834 ml of toluene (1 volume relative to the volume of 10% aqueous caustic soda), stirred the mass for 30 min at 35-45aboutC.

The reaction mass to stand without stirring for 30 min, the toluene layer containing the lipids, mainly cholesterol, separate. Extraction with toluene lipid fraction is repeated in the same conditions.

The combined toluene extract (3204 ml) is treated with activated charcoal 3.2 g (0.1% of the volume of the extract and the purified extract was washed with water 1602 ml (0.5% by volume of toluene extract). Toluene solution is evaporated to dryness, to obtain 2.6 g of dry residue of lipids. The dry residue is dissolved in 96% of the balance) and boil the suspension for 30 minutes The hot solution is filtered. The filtrate is cooled to room temperature and maintained at 62aboutC for 2 hours the Precipitated crystals of cholesterol is filtered and washed on the filter 2 times with 2.6 ml (massouma the ratio 1:1).

Obtain 3.2 g of cholesterol with so pl. 146-149aboutC. the Yield of 0.02% by mass taken for hydrolysis of the gallbladder.

After separation of the hydrolyzed lipid fraction in the reaction mass add 458,5 ml of ethyl alcohol (25% by volume of 10% aqueous caustic soda or 25% alcohol content in the reaction mass) and acidified with concentrated hydrochloric acid to pH 1-2 (517,4 ml). Poured 1834 ml petroleum ether or benzene, or hexane in the volume) and extracted fatty acid, stirring the mass for 30 min at 35-45aboutC. the Top layer of petroleum ether siphoninus. The operation of extraction of fatty acids are repeated twice in the same mode. Petroleum (gasoline or hexane) extract purified with activated charcoal and evaporated to dryness.

Get 144,3 g amount of fatty acids. The output of 9.0% by weight taken on the hydrolysis of the gallbladder.

To the hydrolysate, free of lipids and fatty acids, poured 917 ml of ethyl alcohol (50% by volume of a 10% aqueous solution edcomm 10%-aqueous sodium hydroxide solution). Extraction was carried out for 30 min at 35-45aboutC. Give a shutter speed of 30 min and the extract is separated. The operation of extraction CDCA repeat in the same mode. The combined extract is treated with 1% sodium hydroxide solution 613 ml (massouma ratio of 1:15 to the contents of the CDCA in toluene extract), stirring the solution for 30 min at 20-30aboutC.

An aqueous solution of sodium salt of CDCA is separated, purified with activated charcoal and with vigorous stirring, acidified with 9-10% solution of hydrochloric acid to a pH of 1-3. Fell in the sludge raw CDCA filtered.

Wet sludge raw CDCA dissolved in 1% caustic soda solution in an amount corresponding to 1:100 to the contents of the CDCA in toluene extract. The solution is filtered and to the transparent solution cautiously, in small portions, poured 1% hydrochloric acid to a pH of 6.4 and 6.2. Give exposure for 2 hours Fell in the sludge CDCA filtered off, washed with water with a pH of 6.4-6.2 to a colorless solution of wash water.

The wet sediment CDCA again dissolved in 1% sodium hydroxide solution and re-precipitated as described above. After acidification to give exposure for 2 hours If the pH changes, additionally poured hydrochloric acid to a pH of 6.4 and 6.2.

Sediment Hdcyt in 1% sodium hydroxide solution (in a ratio of 1: 15 to the weight of the wet sediment), carefully poured concentrated sulfuric acid to a pH of 4-4 .5. Falls white curd-like precipitate CDCA. To the suspension is added ethyl acetate in the ratio of 1:3 to the weight of the wet sediment. Extraction was carried out with stirring for 30 min at 20-30aboutC. an ethyl acetate solution is separated. Extraction with ethyl acetate was repeated once more. The combined extract is washed 6% solution of sodium chloride and water, the amount corresponding to 1/5 of the volume of an ethyl acetate extract. The washed extract was purified with activated charcoal, filtered and evaporated to a small volume (1:3 to the contents of the CDCA in an ethyl acetate extract). Evaporated whole volume at once, so that existing in the extract moisture was completely removed from solution or purified extract before parcoy pre-dried with anhydrous sodium sulfate.

In one stripped off the extract at 40-45aboutWith poured in small portions 1 volume of hexane (in relation to the contents of the CDCA in an ethyl acetate extract). Even in a warm solution begin to fall for the crystals. The suspension is allowed to stand for 1 h at 20-30aboutWith, then 10-12 h at 6 2aboutC. Precipitated precipitated crystals CDCA is filtered off and washed on the filter with cold mixture of ethyl acetate:hexane (3: 1) twice in 1 volume to the om, then in air for 6 h in a vacuum drying Cabinet at 60aboutWith vacuum (0,06 MPa) 24 hours

Get 29,56 g in the form of a white granular powder with so pl. 138-145aboutC.

The mother liquor store to highlight the 2nd kristalliset.

29,56 g technical CDCA boil with 295,6 ml dry cyclohexane (1:10 by weight technical acid) 4 h with stirring. Cooled to 20-30aboutC and filtered, washed on the filter 2 times in 29,56 ml of cyclohexane, well-drained, dried in air for 5-6 hours at 20-30aboutWith, then 24 h in a vacuum drying Cabinet at 80aboutWith vacuum (MPa 0,06).

Get 2868 g CDCA with so pl. 160-166aboutWith (within 3aboutC) white powder (specific rotation +11,0 1% solution in ethanol), the content of the basic substance 97,0% 100% product 27,82 g, which is 75% of the content of CDCA in the gall bladders.

The results of the analysis of the obtained samples are shown in table.2.

1. The ALLOCATION METHOD CHENODESOXYCHOLIC ACID FRACTIONS of LIPIDS, CHOLESTEROL AND FRACTIONS of FATTY ACIDS, characterized in that the gall bladders of birds of bile and prorezyami other tissues subjected to alkaline hydrolysis at 94 97oWith the obtained hydrolyzate is treated bipom ratio (0,2 0,25) 1, respectively, relative to the aqueous solution of alkali, used for hydrolysis, the resulting extract containing fraction of lipids with cholesterol as the main component, is separated from the hydrolysate, after cleaning concentrate and excrete cholesterol, hydrolysate containing alkaline salts of fatty and bile acids, is treated with mineral acid to a pH of 1 to 3, then add bipolar extractant, which is a mixture of lower alcohol and malopolyarnoi solvent, taken up in a volume ratio (0,15 0,25) 1, respectively, relative to the aqueous solution of alkali, the resulting extract containing a mixture of fatty acids, is separated from the hydrolysate and after cleaning concentrate and emit a fraction of fatty acids, the hydrolysate containing chenodeoxycholic acid (CDCA) and cholic acid, add bipolar extractant, which is a mixture of lower alcohol and malopolyarnoi solvent in a volume ratio (0,4 0,5) 1, respectively, relative to the aqueous solution of alkali, the resulting extract containing CDCA and cholic acid, is treated with a weak solution of alkali to the resulting salts are mineral acid is added, the resulting mixture CDCA and holeva acid is separated and then CDCA purified from holeva acid by rastra CDCA with Tpl120 123oWith and transfer it in the CDCA with Tpl160 164oC.

2. The method according to p. 1, characterized in that at the stage of allocation fractions of lipids as alcohol use alcohol, and as malopolyarnoi solvent toluene at a volume ratio of the lower alcohol toluene (0.25 to 1).

3. The method according to p. 1, characterized in that at the stage of selection of the mixture of fatty acids as a lower alcohol use alcohol, and as malopolyarnoi solvent petroleum ether, hexane in a volume ratio of 0.25 to 1.

4. The method according to p. 1, characterized in that at the stage of allocation of CDCA as a lower alcohol use ethanol as malopolyarnoi solvent toluene at a volume ratio of 0.5 to 1.

5. The method according to p. 1, characterized in that the translation of the low-melting CDCA with Tpl120 123oWith high-melting CDCA with Tpl160 - 164oWith carried out by dissolving the first (Tpl120 - 123o(C) in a weak alkali solution, acidification of the reaction mixture with a mineral acid to a pH of 4 to 4.5, extracting it with an organic solvent, concentrating it and add to the residue malopolyarnoi solvent followed: the m solvent with Ttoandp60 140oC.

 

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2 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel fusidic acid derivatives of general formula [I], where X represents halogen, trifluoromethyl, C1-C7alkyl, substituted with phenyl, C2-C9alkenyl, optionally substituted with C1-C7alkyl, halogen or phenyl, phenyl, optionally substituted with one or two similar or different substituents, selected from group consisting of halogen, C1-C7alkyl, C2-C9alkenyl, phenyl, C1-C6alkoxy, nitro, C1-C6alkyltio, trifluoromethyl and cyano; or X represents naphtyl; Y and Z both represent hydrogen or together with bond C-17/C-20 form double bond between C-17 and C-20 or together represent methylene and form cyclopropane ring in combination with C-17 and C-20; A represents O, S or S(O); B represents C1-6alkyl, C2-6alkenyl, C1-6acyl, phenyl or benzoyl, where C1-6alkyl is optionally substituted with one or more halogens, hydroxy, C2-6alkenyl, phenyl, C1-4heteroaryl or C1-6alkoxy; Q1 represents -(CHOH)-, or -(CHW)-, where W represents halogen or azido; Q2 represents -(CHOH)-; to their pharmaceutically acceptable salts and easily hydrolysed esters and to pharmaceutical compositions, including said derivatives, as well as to their application in therapy.

EFFECT: application in therapy.

31 cl, 127 ex, 5 tbl

FIELD: production processes.

SUBSTANCE: invention refers to wood working and wood chemical industries. Birch bark is broken down, mixed with liquid, the mixture is held at temperature higher than mixture freezing temperature, then triterpene compounds are separated from lingo-adipic residue with the following filtration and drying. Birch bark is additionally broken down by method of impact-abrasing and/or abrasing effect till obtaining birch bark flour. Birch bark flour is mixed with liquid with density of 0.999-0.958 kg/m3. Mixture is held for 0.1-10 hours and then separated by flotation to hydrophobic and hydrophilous fraction. Solution remaining after separation is condensed and dried. Obtained hydrophobic fraction - mixture of triterpene compounds - is exposed to recrystallisation in ethanol with activated charcoal and then betuline, solution of triterpene compounds in ethanol and mixture of triterpene and polyphenol compounds at carbon matrix is obtained. Or triterpene compounds mixture is separated to fractions in carbon-dioxide extractor and betuline, dry mixture of triterpene and polyphenol compounds are obtained. Hydrophilous fraction - lingo-adipic flour - is separated from liquid and dried out.

EFFECT: increase of environmental safety and method effectiveness.

6 cl, 4 ex, 3 dwg

FIELD: medicine.

SUBSTANCE: present invention presents a preparation to reduce insulin resistance. The preparation contains 3-O-v-D-glucopyranosyl-4-methylergost-7-ene-3-ole, or an extract made with using an organic solvent, or an extract made with using hot water, or a drained liquid of a plant of Liliaceae family, or fraction thereof which contains this compound as an active component.

EFFECT: production of the preparation which is suitable for inhibition of adipocytokine production, particularly adipocytokine which cause insulin resistance, and for prevention of pathological conditions caused by insulin resistance, or simplification of clinical course of said pathological conditions.

9 cl, 3 ex

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