The method of receiving glycyram

 

(57) Abstract:

Usage: in the chemistry of amino acids, in particular in the way of getting monoammonium salts of glycyrrhizic acid(glycyram). The inventive product is monoammonium salt of glycyrrhizic acid(glitsiram), so pl. 202 - 204o(With Razlog.), yield 6%. Reagent 1: powder of licorice roots. Reagent 2: an aqueous solution of alkali and bubbling oxygen. Reagent 3: sulfuric acid. Reagent 4: 25% solution of ammonium hydroxide. Reaction conditions: after the sequential interaction of the reagents are recrystallization of glycyram from a mixture of ethanol and acetic acid.

The invention relates to chemical-pharmaceutical industry, in particular to a method for monoammonium salt glitzirrizinova acid to glycyram used in medicine as a medicinal product.

A method of obtaining the glycyram treatment of dry extract from the roots of licorice (Glycyrrhiza glabra L.) 10-fold excess of acetone containing 2.5% to 3% sulfuric acid. After filtration, the acetone solution glitzirrizinova acid alkalinized 25% NH4OH to pH 7.5-8. Released triammonium salt glitzirrizinova acid is boiled with ice exutive coal [1]

This method has several disadvantages, such as low yield of glycyram (4,75% by weight of licorice roots), duration, energy and intensity of the process, due to repeated extraction of licorice roots and processing a variety of solvents and reagents, the need for repeated removal of the solvent and its disposal. Use the cleanup phase of glycyram 15-fold excess of 85% ethanol with 3% active carbon additionally complicate and clutter the process, causing the need for separation of used coal and its utilization. The formation of a large number of adverse ammonium sulfate in a mixture with glitsiramom is also a disadvantage of this method.

A method of obtaining the glycyram that includes six stages. The dry extract obtained from licorice root, dissolved in water at 70-80aboutC for 3 h, then a solution of 20% H2SO4precipitated glitzirrizinovu acid, which is dissolved in acetone, treated with 25% solution of NH4OH and get triammonium glitziest. The last process threefold excess of 80% acetic acid and get soggy glitsiram. The crystals formed of glycyram washed with 95% Atilla [2]

This method also has some significant drawbacks: output even crude of glycyram is only 2.25% by weight of the feedstock. The method is energy-intensive. I, II, IV and VI stage is carried out at temperatures of 70-90aboutBack To serious disadvantages of this method include the use of large quantities of reagents. So, to receive one percent of glycyram spent 100 l 25% NH4OH, 100 l of acetone, 10 l of 80% acetic acid and 152 l of ethanol.

The closest to the invention is a method of obtaining glycyram by which fresh liquorice fermented at 36-38aboutAnd processing it through 26 h excess of 0.5% solution of NH4OH and then filter the extract and disembarking from it raw glitzirrizinova acid with concentrated H2SO4. After filtering and drying, the crude glitzirrizinovu acid is ground up and treated with a threefold excess of boiling acetone. The acetone solution with addition of 25% aqueous NH4OH wikidot triammonium glitziest, which is filtered, washed with acetone and directly on the filter is dissolved in a threefold excess of glacial acetic acid, and from the filtrate by recrystallization allocate raw the technical glycyram is 54-63 PM In addition, the phase filter ammonia extract of licorice roots lasts more than 24 hours, which significantly increases the total duration of the process of obtaining technical glycyram, which is 78-87 including Another disadvantage of this method is the use of a threefold excess of glacial acetic acid in the stage of transformation of diammoneglycyrrhizinate in glitsiram. This circumstance leads to the great expense and loss of acetic acid. As a result, the question of utilization of waste acetic acid in the amount of 600 kg per ton of licorice. In addition, the processing of diammoneglycyrrhizinate glacial acetic acid on the filter in static conditions does not provide a full cleaning of glycyram. Output technical glycyram equal to 12,5-14,0% and after cleaning, the output is 2.5 to 3.2%

The aim of the invention is to accelerate the extraction process licorice aqueous-alkaline solution, reducing consumption of glacial acetic acid and increase the yield of dry extract of licorice and pure glycyram.

The objective is achieved by way of extraction of finely ground roots of licorice aqueous solution of sodium hydroxide is carried out in the presence of oxygen in the air supplied in the region of linearizing acid is treated with boiling acetone, to the acetone extract was added with stirring 25% NH4OH, then, after separation of the acetone released tramadolgeneric treated with ethyl alcohol and glacial acetic acid with vigorous stirring and boil for 30-40 minutes, then allocate glitsiram.

The major difference of the proposed method is the implementation of the extraction of licorice roots aqueous-alkaline solution in the presence of oxygen supplied to the reaction mass with a speed of 60-80 l/h for 5-6 hours a Stream of oxygen, intensificar diffusion (adsorption-desorption) processes in plant tissues, speeds up and reduces the duration of the extraction of polyphenols and glycyrrhizic acid. And oxygen, subjecting the polymerization (or oxidative politanschii) an alcoholate of natural phenols, leads to an increase in their molecular mass and deterioration of solubility in acetone. Due to this circumstance, the extraction mixture triammonium salts of glycyrrhizic acid and polyphenol content of dissolved polyphenols significantly reduced in boiling acetone. For this reason, the amount of glacial acetic acid necessary to convert triammonium salt glicerol, the flow of oxygen accelerates the process of extraction of licorice roots, reduction of consumption, glacial acetic acid, to increase the yield of dry extract of the plants and clean glycyram.

P R I m e R 1. In enameled reactor equipped with a reflux condenser and a bubbler, download 4,975 kg of water, 0.025 kg of sodium hydroxide and 1 kg of the powder of the roots of licorice (particle size 1-2 mm). Through the mixture using a bubbler with a speed of 80 l/h for 5 h breathable. The extract separated on the filter under a weak vacuum. Plant residue on the filter is washed with water 5-7 l, the washing water combined with the extract. The duration of the process of filtration and washing is 6-7 hours, the Extract is transferred into a reactor and at a weak bubbling air (or stirring with a mechanical stirrer) to it within 10-20 min add concentrated H2SO4to the acid environment. Then, the solution is left on lees for 5-6 hours After which the top of the water portion of the precipitated crude glycyrrhizic acid sifonios, and to the suspension is poured another 5 liters of water, stirred thoroughly and filtered under a weak vacuum. Glycyrrhizinic acid is dried at 60-70aboutC for 5 h with 10-1mm is), subjected to four times of extraction with boiling acetone (320-340 ml) for 20 min each time. Next, the acetone is separated using a filter-fungus under a weak vacuum. After the fourth extraction of the reaction mixture is transferred into the filter and carefully filtered. To the acetone extract was added with stirring to 40 ml of 25% aqueous NH4OH to pH 7.5-8. Landed in this tramadolgeneric filtered, washed with 50 ml of acetone and transferred into a three-liter reactor equipped with a stirrer and reflux condenser. To it add 1260 ml of 96% ethyl alcohol and 252 ml of glacial acetic acid and with vigorous stirring, boil for 30 minutes Then use filter-fungus sucked off an elaborate mixture of ethyl alcohol and acetic acid. The crystals of glycyram into the reactor again add 1260 ml of ethanol and 25 ml of glacial acetic acid, boiled for 30 min, cooled, and then filtered under a weak vacuum, crystals of glycyram washed with 200 ml of ethyl alcohol and dried at 50-60aboutC. the Yield of pure glycyram is 602 g (6%), pl. 202-204aboutC (with decomposition).

The purity of synthesized glycyram was controlled by liquid chromatography device KOVO (sorbent Separon SGX-C18, concentration in the BR>
UV - and PMR-spectra of the obtained sample of glycyram were identical with the same parameters of glycyram synthesized in VILR.

P R I m e R 2-4. In contrast to example 1, using 0.25; 0.75 and 1.0% aqueous solutions of NaOH. After you receive appropriate treatment dry extract 20, 32, and 33% glitsiram 4,1; 5.9 and 6.0%, respectively.

P R I m e R 5-7. In contrast to the conditions of example 1, the feed rate of air through the mixture of particles licorice and an aqueous solution of alkali equal to 50, 60, and 90 l/h Output dry residue is 20, 28, and 30% of glycyram at 3.9 5.8 and 6.1%, respectively.

Thus, as can be seen from the results of the experiments are optimal conditions of experience as in example 1, where the initial NaOH concentration is 0.5% and air velocity 60-80 l/h High basicity of sodium hydroxide and extremely efficient mixing of the extract using a stream of air helps to deepen and accelerate the extraction of polyphenols and glycyrrhizic acid. As a result, the yield of dry extract (crude glycyrrhizin acid) reaches 28-30% 10-12% higher extract yield in the prototype, and the duration of the stage of obtaining a dry extract, compared with the prototype, is reduced by 36 PM

Oxygen is Yu an important role. According to known literature data [4,5]phenols in the presence of alkali, reacting with oxygen, into high molecular weight phenols, as a result of natural polyphenols included in the aqueous alkaline extract of licorice are oxidized by oxygen in the air, turn into even more high molecular weight and insoluble substances, which is confirmed by determining the MMP and MM polyphenols by-product of the proposed process. MM polyphenols after oxidation is 760 (before oxidation 325-370). Therefore, in the stage of extraction of the dried extract of boiling acetone the number of unwanted polyphenols significantly reduced in the extract and increases the amount of glycyrrhizic acid. This greatly facilitates purification stage of glycyram, reduces the consumption of glacial acetic acid in the processing phase, triammonium of glycerinate 5 times and increases its output. The output of glycyram is 6% vs. 2.5-3.2% in the prototype.

The results obtained glycyram methods of liquid chromatography, PMR and spectrophotometric evidence of its high purity (99%).

The METHOD of RECEIVING GLYCYRAM extraction powder licorice root aqueous solution of alkali, followed in the second acid 25% solution of NH4OH and processing the received triammonium glycyrrhizate glacial acetic acid, characterized in that the extraction of licorice roots is carried out in the presence of oxygen in the air supplied into the reaction mass at 60 - 80 l/h for 5 to 6 hours

 

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