The method of obtaining glycyrrhizic acid

 

(57) Abstract:

Usage: as a drug, possess a set of valuable medical properties. Essence: glycyrrhizin acid, which is obtained from technical dry extract of licorice with the content of glycyrrhizic acid 26-28% by extraction with acetone containing 0.1% sulfuric acid at room temperature with getting trikalinos salt glycoside and its transfer to odnoklikovoy salt by recrystallization of the latter from aqueous ethanol twice with a ratio, respectively (5:1, V/V), and then transfer to glycyrrhizinic acid by treating odnoklikovoy salt 1% solution of sulfuric acid at 98-100oC and chloroform at room temperature. The obtained crystalline white precipitate glycyrrhizic acid contains 87-89% of the basic substance. 3 Il.

The invention relates to a method for producing triterpene glycoside - glycyrrhizic acid (GA) is the main ingredient of licorice (liquorice) (Glycyrrhizae glabra and Glycyrrhizae uralensis), with valuable medical properties [1-3]

Currently available raw material for producing glycoside are extracts of licorice thick and su is the substance of monoammonium salts of glycyrrhizic acid (glitsiram), produced BY "Cementboard" and Kharkiv ON "Health workers". The method of obtaining pure Ledger of glycyram was proposed by us earlier [5]

Previously proposed a method of obtaining a Ledger from the extract of licorice thick according to the following scheme [6] (prototype) (see Fig.1).

Licorice extract thick (30 kg) was dissolved in 0.5% NaOH (150 l), besieged the crude glycoside adding 25% H2SO4to the acidic reaction in the Congo, the precipitate was filtered with water and dried at 40-50oC. Output technical glycoside 9.6 kg (basic substance content 25-28%

Received technical glycoside were extracted with 50oC acetone, besieged TRACELEVEL salt (3K-salt) glycoside addition of 15% aqueous alcohol solution of KOH to weakly alkaline reaction, the precipitate LC-CC salt was aspirated, washed with acetone and dried.

The residue was dissolved in 75% EtOH (100 g ZK-salt 1.5 l) was treated with cation exchange resin KU-2 (H+-form) in the ratio 1:1 (by weight) and activated charcoal.

After the salt is completely dissolved, the solution was filtered and evaporated to dryness in vacuum at 40-45oC. the Output of the glycoside 80-82 g per 100 g ZK-salt (to 91.1-93,4ofrom theory or 40-45% of the raw material).

The content of the basic substance in the glits the UB>D0= +50ethanol).

The main disadvantage of this method of producing hyaluronic acid is a low content of basic substance in the resulting product (amorphous), which does not exceed 65-70% according to VSGH (chromatograph Du Pont, column reversed-phase-Bondapak C-18, mobile phase: H2O-CH3CN-MeOH-AcOH 44:35:20:1 (v), UV detector, l 254 nm).

In the proposed method the proposed receipt Ledger of technical dry extract of licorice with the content of glycyrrhizic acid 26-28% (according to HPLC), which was extracted with acetone containing 0.1% H2SO4at room temperature, then with acetone boiling, got TRACELEVEL salt (SC-g) of the glycoside by treatment with 10% methanol solution of KOH, the latter was transformed into odnoklikovoy salt (1K-salt by recrystallization from glacial acetic acid at 95-100oC, 1K-salt was recrystallized 2 times from aqueous ethanol (5: 1, v/v) and treated with 1% solution of H2SO4when 100oC, and then chloroform at room temperature. The output of glycyrrhizic acid 47-48% in terms of raw materials licorice with a GC content of 26.6% of the basic substance Content in the received CC 87-89% according to HPLC (chromatogra the 254 nm).

Distinctive features of the proposed method:

1. Use the 1st stage for the extraction of technical dry extract of licorice acidic acetone (with addition of 0.1% H2SO4), while in the method-prototype 1-th stage licorice thick dissolved in 0.5% solution of alkali).

2. Put the transfer operation 3K-CC salt in 1K-salt by recrystallization from glacial acetic acid at 95-100oC, which increases the degree of purification of the resulting glycoside.

3. Entered operation recrystallization 1K-CC salt from aqueous ethanol (5: 1, v/v) (2 times).

4. At the stage of transfer of salt in the acid, we used the processing of pure 1K-CC salt 1% solution of H2SO4when 98-100oC instead of a cation exchange resin KU-2 (H+) in 75% aqueous ethanol, as in the method prototype.

This operation gives the possibility to obtain crystalline white precipitate glycyrrhizic acid, which after treatment with chloroform to remove impurities aglycone is the content of the basic substance 87-89% while in the method prototype glycoside 65-70% purity and obtained amorphous.

Scheme for glycyrrhizic acid from dry extract of licorice shownC);

[]2D0= + 60 to +65(C = 0,04; MeOH)

The content of the basic substance 87-89% according to HPLC, the content of H2O 5,4-6,0%

In Fig.3 shows the HPLC chromatogram of the extract of licorice dry (Ural plant): liquid chromatograph Du Pont, column reversed-phase-Bondapak C-18, mobile phase: H2O-CH3CN-MeOH-AcOH 40:35:20:1 (v), UV detector (l 254 nm); flow rate

The content of glycyrrhizic acid in the extract 26,60,7%

Example 1.

370 g technical dry extract of licorice with the content of glycyrrhizic acid approximately 27% were loaded into a flask, equipped with a mechanical stirrer and reflux condenser, was added 1000 ml of acetone, 10 ml of a solution of H2SO4(1 ml of H2SO410 ml of acetone and stirred at room temperature for 3 hours the Acetone extract was decanted by decantation, the precipitate was added to 500 ml of fresh acetone and boiled with stirring for 3 hours the Acetone extract was decanted, the residue was extracted with 500 ml of acetone at boiling (2 hours). This operation was repeated 2 more times (500 ml). Got 3000 ml of acetone extract was filtered, evaporated to 1000 ml and dried over MgSO4. To the concentrated solution of the glycoside added with stirring 300 is yli 2 times in 500 ml of acetone, 500 ml of methanol and was dried in air, then in an oven at 100-110oC. Received 222 g technical 3K-CC salt, which was dissolved by heating to 95-100oC in 2200 ml of glacial acetic acid (BOW), filtered, and left to crystallize at room temperature overnight. Precipitate odnoklikovoy salt (1K) Ledger was filtered, washed with 500 ml ONION, 500 ml methanol, 500 ml of ether and dried. Received 103 g (100% ) 1K-CC salt, which recrystallize 2 times from ethanol-water (5:1, v/v). The yield of pure 1K-salt Ledger 62 g (60.2% in terms of raw materials). []2D0+ 50o(c 0,06; 25% tOH). UV25%poppyS.tOH (lg)): 255 nm (3,90). IR , cm-1: 3600-3200 (OH); 1720, 1710 (COOH); 1630-1600 (COO-). Found To Equal To 4.97. C42H61O16R. Calculated To 4,54.

62 g 1K-CC salt and 600 ml of 1%aqueous solution of H2SO4was heated at 98-100oC 20 min, held at room temperature for 3 h and the white precipitate was filtered Ledger. Washed with water, dried in air, then at 110-120oC. Received a 50.5 g of glycoside, which was stirred 1 h in 500 ml of chloroform, filtered, and dried in vacuum at approximately the 60oC. Output SC 49 g (49,8% based on the feedstock). So pl. 214-215oC; []2D0+62o(0,04; MeOH). UVPMC with reversed phase-Bondapak C-18; mobile phase: H2O-CH3CN-MeOH-AcOH 44:35:20:1 (v); UV detector l 254 nm). The water content of 5.92%

Example 2.

370 g of technical licorice was filled with 1000 ml of acetone, was added 10 ml of a solution of H2SO4(1 ml of H2SO4in 10 ml of acetone in acetone and stirred at room temperature for 3 hours the Acetone extract was decanted by decantation, the precipitate was added to 1000 ml of acetone and boiled under stirring for 3 hours the Acetone extract was decanted, the residue was added 800 ml of acetone and boiled for another 2 hours combined acetone extracts (2800 ml) was filtered, evaporated to 800 ml. To concentrated acetone extract was added to 200 ml of 10% methanolic solution of KOH (pH 8), sediment 3K-CC salt was filtered, washed with 500 ml of acetone, 500 ml of alcohol, 500 ml of ether and dried in air, then at 100-110oC. Got 221 g 3K-CC salt, which was dissolved pri heated to 95-100oC in 2200 ml ONIONS, filtered, and left to crystallize overnight. Sediment 1K-CC salt was filtered, washed with 500 ml ONION, 500 ml methanol, 500 ml of ether and dried. Received 102 g (99%) 1K-CC salt, which recrystallize 2 times from ethanol-water (5:1, v/v). The yield of pure 1K-CC salt 60 g (58.2% in terms of raw materials). 60 g 1K-CC salt and 600 ml of 1% solution of H2SO4o
C. Output SC 48 g (48.8% in terms of raw materials). So pl. 219-220oC; []2D0+60o(0,04; MeOH). UVtmACA.OH(lg): 250 nm (4,05). The content of the basic substance of 88.6% of the water Content of 5.92%

The method of obtaining glycyrrhizic acid, comprising the extraction step technical dry extract of licorice with acetone to obtain trikalinos glycoside salts by treatment of the extract with an alcohol solution of KOH, characterized in that the dry extract of licorice with the content of glycyrrhizic acid 26-28% extracted with acetone containing 0.1% sulfuric acid at room temperature, then with acetone boiling received TRACELEVEL salt glycoside transferred to odnoklikovoy salt by recrystallization from glacial acetic acid at 98 100oWith subsequent recrystallization of the latter from aqueous ethanol twice at a ratio of 5 to 1 volume/volume and then transfer to glycyrrhizinic acid by treating odnoklikovoy salt 1% solution of sulfuric acid at 98 100oand chloroform at room temp

 

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