Method of extraction of acidslactam antibiotics

 

(57) Abstract:

The allocation method-lactam antibiotics from aqueous solutions relates to the field of medicine, specifically to the production of biologically active substances. The purpose of the invention is to increase the output and quality-lactam antibiotics. This goal is achieved by the fact that during the precipitation of acid antibiotics from aqueous solution by the action on it of mineral acid to the aqueous solution is added an organic solvent sparingly soluble in water, in an amount of from 1.1 to 10 vol.%. 1 C.p. f-crystals.

The invention relates to chemical-pharmaceutical industry, namely the selection of the acid penicillin and cephalosporin antibiotics from aqueous solutions after receiving their biological or chemical synthesis, and used for chemotherapy of bacterial infections.

Known methods of selection-lactam antibiotics in the form of the acids or their salts (K, Na, and others), consisting in the extraction of the antibiotic from aqueous solution by organic solvents (ethyl acetate, butyl acetate, methylene chloride, and others) with subsequent precipitation of the desired product from an extract of the action of K acetate (Na), potash or ethylhexanoate Na(K). Received is is the complexity and multi-stage process and the use of large amounts of organic solvents.

There are also known methods of isolation-lactam antibiotics from aqueous solutions, based on the deposition of acids, antibiotics introduction in a solution of mineral acid with the subsequent transfer of the resulting acid potassium or sodium salt.

Closest to the claimed effect is achieved is the allocation method, which consists in the deposition of acid antibiotics from aqueous solution with addition of organic solvents, sparingly soluble in water.

The main disadvantages of these methods are:

1) less output of antibiotic compared with extraction methods, not exceeding 85%, due to the large loss of product from the mother liquor;

2) eye-catching acid antibiotic is different crystalline or amorphous structure, which makes filtering the suspension and drying the paste obtained product;

3) acid antibiotic seacadets a significant amount of impurities and pigments, resulting in the content of the basic substance is precipitated product does not exceed 75%.

The inventive method is directed to the reduction or complete elimination of these drawbacks.

The aim of the invention is to obtain acid and the camping due to the fact, that significantly improve conditions of crystallization of the acid antibiotic, this increases the selectivity of the deposition process and decreases the residual content of the target product in the mother solution.

The hallmark of the proposed method is added to aqueous solution or suspension of the antibiotic organic solvent sparingly soluble in water, in an amount not less than 1.1%, but not more than twice its solubility in the aqueous solution of the antibiotic.

The most suitable are organic solvents with a solubility in water of from 0.5 to 10 vol.%. Among them are such as ethyl acetate, propyl, butyl acetate, butanol, amilal, methylene chloride, chloroform, etc.

The proposed solution allows you to select an antibiotic with access and quality close to extraction methods, while maintaining the simplicity of the methods for the isolation of acid antibiotic added to aqueous acid solution.

Example 1. To 1 liter native solution dentists (FMP) with the content of the SEF to 1.25% poured 15 ml of methylene chloride, stirred to obtain a homogeneous solution and precipitated technical FMP acid by the action of a solution of 6%-nya temperature of the suspension 8-12oC. after aging the suspension is filtered, pasta technical FMP-acid washed with 100 ml of water and dried at 40oC to constant weight. Obtain 14.3 g technical FMP acid with a basic substance content of 80%. The output from the native solution 95,1%.

Example 2. To 1 liter of native SEF solution, pre-filtered through a membrane filter with a pore size 10000-15000 D, with the content of the SEF to 1.25% poured 6 ml of methylene chloride, stirred to obtain a homogeneous solution, poured 6% solution of sulfuric acid to a pH of 2.8, then poured another 6 ml of methylene chloride and continue acidification to pH 1.5 to 2.0, stirred for 2 hours at a temperature of 8-10oC. after aging the suspension is filtered, pasta technical FMP-acid washed with 100 ml of water and dried at 40oC to constant weight. Obtain 14.8 g technical FMP-acid content of the main substance of 86%. The output from the native solution 97,2%.

Example 3. To 1 liter of native SEF solution with the content of the SEF 0,546%, with vigorous stirring simultaneously from two drip funnels poured 13 ml of butyl acetate and the solution acidified with 10% hydrochloric acid until the pH value of the suspension from 1.5 to 2.0, is maintained at the ASTA technical acid washed with 100 ml of water and dried at 40oC to constant weight. Get 6,05 g technical FMP-acid content of the main substance of 84%. The output from the native solution of 93.1% of.

Example 4. To 1 l of the native solution of benzylpenicillin (BP) with BP 0.9 per cent poured 16 ml isoamylase, poured a solution of 10% hydrochloric acid to pH 1.5-2.0, incubated for 16 hours at a temperature of 0 to 3oC, the suspension was filtered, the paste is washed with 50 ml of water, dried at 40oC to constant weight. Get 7,97 g technical BP-acid content of the main substance of 78%. The output from the native solution is 70.1%.

Example 5. To 1 liter of water of the reaction mass after receiving tsefalotina containing 7.0% of tsefalotina, poured in 35 ml of methylene chloride, stirred for 10 min to obtain a homogeneous emulsion, 5oC is slowly added 10% hydrochloric acid to pH 1.5 to 2.0, the resulting suspension is stirred for 4 h, after which the precipitated crystals filtered, washed with 80 ml of water, dried at 50oC to constant weight. Get 60,9 g cefalotin-acid content of the basic substance of 97.3%. Exit at the stage of deposition of 84.7 per cent.

1. Method of extraction of acid-lactam antibiotics from aqueous solutions by precipitation of the mineral acid is th solution or suspension of the antibiotic is added to an organic solvent, sparingly soluble in water, in an amount not less than 1.1%, but not more than twice its solubility in the aqueous solution of the antibiotic.

2. The method according to p. 1, characterized in that the organic solvents, sparingly soluble in water, used solvents with solubility in aqueous solution of the antibiotic 0.5 to 10 vol.%.

 

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