The way to select phenoxymethylpenicillin acid

 

(57) Abstract:

Usage: biotechnology, production of antibiotics. The inventive method of allocating phenoxymethylpenicillin acid involves filtering the culture fluid, the deposition from the native solution of the technical phenoxymethylpenicillin acid, its dissolution in acetone to a concentration of 100,000 - 200,000 IU/ml, subsequent filtration and isolation of the target product. 2 C.p. f-crystals,

The invention relates to biotechnology and relates to a method of obtaining biologically active substances (BAS), namely to receive the dentists used as an intermediate product to obtain a semisynthetic B-lactam antibiotics and chemotherapy of bacterial infections.

Known methods for producing dentists, consisting in the extraction of the antibiotic from native solution of organic solvents, mainly butyl acetate, and the deposition of the intermediate product from the extract by the action of potassium acetate or potassium with subsequent selection FMP acid (U.S. Pat. Russia N 17264796, CL C 07 D 499/16; U.S. Pat. Czechoslovakia N 124845; U.S. Pat. Czechoslovakia N 127853; industrial regulations on production phenoxymethylpenicillin process, the use of large amounts of organic solvents, the use of various types of raw materials.

In addition, the product (salt and SEF acid) obtained by the above methods, contains an admixture phenoxyalkanoic acid, which produces a lower output when receiving 6-aminopenicillanic acid.

Known such methods of obtaining dentists from native solution-based deposition of technical FMP acid by the introduction of a mineral acid in sodium solution, followed by dissolving technical acid in an organic solvent and precipitation from the solution obtained dentists To salts (U.S. Pat. USA N 4354971, class C 07 D 499/18; A. S. Czechoslovakia N 185103, class C and 121 D 9/12).

The closest in technical essence and the achieved result is a method for dentists outlined in the ed.St. Czechoslovakia N 185103 consisting of using as the source of raw materials of technical FMP allocated from native solution by the action of hydrochloric acid. Dried technical product twice suspension in butyl acetate, resulting in a gain SEF solution in butyl acetate with activity 31,600 units/ml of the obtained solution Clevo is whether SEF from reextract.

The disadvantages of this method are the multistage process, significant costs for raw materials, environmental pollution due to the use of large volumes of organic solvents (butyl acetate, butanol).

These disadvantages are completely eliminated in the present method of selection of dentists.

The aim of the invention is to increase the output and quality dentists, improving the environment, reducing the cost of production.

This goal is achieved by what is known of the process is eliminated several stages, leading to the loss of the antibiotic (dual suspension technical acid in butyl acetate, reextracted antibiotic aqueous solution of potassium acetate, followed by salting out K-salt).

Distinctive features of the proposed method is used for dissolving technical FMP-acid organic solvent miscible with water, for example acetone, and crystallization FMP acid from water-acetone mixture.

Example 1.1.Dissolution technical FMP acid.

58 g technical FMP acid and the -20oC, filtered off from nerastvorimogo precipitate protein impurities, wash the precipitate with 70 ml of acetone.

Get 710 ml acetone concentrate dentists activity 113718 μg/ml, the content of dentists 80,74 million units of Output at the stage of dissolution 96%

2. Clarification of acetone concentrate.

To the resulting clarified concentrate FMP added 16.5 g of activated charcoal brand OS-And stirred the reaction mass 20 min, filtered off from the coal, the coal is washed on the filter with 50 ml of acetone, receive 750 ml clarified acetone concentrate activity 105, 506 ág/ml, the content of dentists of 79.13 million units of chromaticity of 0.18.

The output stage of clarification 98%

3. Crystallization FMP acid.

To 750 ml of clarified acetone concentrate add 1500 ml of demineralized distilled water, cooled the reaction mass to 5 - 10oC and maintained at this temperature and stirring for 2 to 4 h until the residual activity of the stock solution of no more than 1000 IU/ml

This activity values of the reaction mass is filtered, the residue washed with 200 ml of desalted (distillirovanna the capacity of 1680 μg/mg, the content of the SEF 74,38 million units Output stage 94,0% yield from technical FMP acid 887,44%

Example 2. Analogously to example 1, but the dissolution technical FMP-acid lead from the calculate activity acetone concentrate approximately 200,000 ág/ml and used at the stage of crystallization of 4 volumes of water relative to the volume of acetone concentrate.

Example 3. Analogously to example 1, but using at the stage of dissolution of isopropyl alcohol.

Example 4. Dissolution technical FMP acid analogously to examples 3,2 (isopropyl alcohol, the concentration of antibiotic 200,000 ág/ml).

Example 5. Analogously to example 1, but using at the stage of dissolving butyl alcohol.

Example 6. Dissolution technical FMP acid analogously to examples of 5.2 (butyl alcohol, the concentration of antibiotic 200,000 ág/ml).

1. The way to select phenoxymethylpenicillin acid comprising filtering the culture fluid, the deposition from the native solution of the technical phenoxymethylpenicillin acid, its dissolution in an organic solvent, filtering and selection of the target product, characterized in that the dissolution of the technical phenoxymethylpenicillin acid Prov is the amount of organic solvent, miscible with water, use acetone.

3. The method according to p. 1, characterized in that the dissolution of the acid in an organic solvent is carried out until the concentration of 100000 200000 IU/ml

 

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