A kind of method for preparing cefaclor by enzymatic method

A technology for preparing cefaclor and an enzymatic method, which is applied in the field of biomedicine, can solve the problems of unfavorable expansion of production and wide application of cefaclor, high solvent residue and insufficient purity, and achieves the advantages of good crystal shape, uniform crystal and shortened process route. Effect

Active Publication Date: 2020-12-29
长沙凯晓生物科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The chemical condensation method of the prior art has problems such as complex process, high cost, large pollution, high solvent residue and low yield, and the traditional enzymatic method also has shortcomings such as insufficient purity, which is not conducive to the expanded production and wide application of cefaclor , how to improve the purity of cefaclor when using enzymatic method to prepare cefaclor needs to be further explored

Method used

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  • A kind of method for preparing cefaclor by enzymatic method

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Embodiment 1

[0027] A method for enzymatically preparing cefaclor, comprising the steps of:

[0028] (1) Dissolve 40g of 7-amino-3-chloro-cephem acid solid with ammonia water at 18°C ​​to obtain a mother nucleus solution, add D-p-phenylglycine methyl ester hydrochloride solution to the mother nucleus solution to obtain a reaction solution, Among them, the D-p-phenylglycine methyl ester hydrochloride solution contains 41.3 g of D-p-phenylglycine methyl ester hydrochloride, adjust the pH to 6.5, cool down to 15 ° C, add 40 g of immobilized cefaclor synthase, and stir the reaction After 20 minutes, 0.1 g of cefaclor was added as a seed crystal, and after 30 minutes, D-p-phenylglycine methyl ester hydrochloride solution was continuously added dropwise for 2 hours at a rate of 1 mL / min. During the reaction, 7-amino-3-chloro - the residual amount of cephalosporin, and control the pH of the solution in the reaction process with 6mol / L hydrochloric acid and 3mol / L ammonia to be 6.5, and keep the r...

Embodiment 2

[0034] A method for enzymatically preparing cefaclor, comprising the steps of:

[0035] (1) Dissolve 40g of 7-amino-3-chloro-cephem acid solid with ammonia water at 18°C ​​to obtain a mother nucleus solution, add D-p-phenylglycine methyl ester hydrochloride solution to the mother nucleus solution to obtain a reaction solution, Among them, the D-p-phenylglycine methyl ester hydrochloride solution contains 41.3 g of D-p-phenylglycine methyl ester hydrochloride, adjust the pH to 6.5, cool down to 15 ° C, add 40 g of immobilized cefaclor synthase, and stir the reaction After 20 minutes, 0.1 g of cefaclor was added as a seed crystal, and after 30 minutes, D-p-phenylglycine methyl ester hydrochloride solution was continuously added dropwise for 2 hours at a rate of 1 mL / min. During the reaction, 7-amino-3-chloro - the residual amount of cephalosporin, and control the pH of the solution in the reaction process with 6mol / L hydrochloric acid and 3mol / L ammonia to be 6.5, and keep the r...

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Abstract

The invention discloses a method for preparing cefaclor from an enzyme process. The method comprises the following steps: preparing cefaclor coarse powder from 7-amino-3-chloro-cephem acid, D-o-phenylglycine methyl ester hydrochloride, immobilized cefaclor synthetase and cefaclor crystal seed; dissolving and discoloring the cefaclor coarse powder, adding the cefaclor crystal seed to regulate the pH value, stirring for a first time to grow the grains, and stirring for a second time to grow the grains after regulating the pH value, thereby preparing a crystal mixed solution; performing the suction filtration on the crystal mixed solution to obtain a crystal product and crystallized mother liquor; and sequentially performing washing with water, soaking washing, suction filtration and vacuum drying on the crystal product to obtain cefaclor. The method for preparing cefaclor from the enzyme process has twice stirring grain-growing operation, and the cefaclor slowly separates out in a re-crystallizing process, and the prepared crystal is uniform and is better in crystalline form; and the prepared cefaclor has very high purity greater than 99.7%.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a method for preparing cefaclor. Background technique [0002] Cefaclor is a semi-synthetic second-generation oral cephalosporin antibiotic drug. Cefaclor was approved by the FDA in 1979 and successfully launched in the United States in 1982. Because of its broad-spectrum, high efficiency and good clinical safety It has become one of the important drugs for the treatment of bacterial infections. The bactericidal mechanism of cefaclor is to inactivate transpeptidase, interfere with the synthesis of the final stage of the bacterial cell wall, prevent the cross-linking of mucopeptides, and treat Gram-positive bacteria such as Staphylococcus, Streptococcus, Pneumococcus and Escherichia coli Gram-negative bacteria have a strong killing effect. [0003] The industrial preparation method of cefaclor is to use 7-amino-3-chloro-cephalosporin acid (7-ACCA) and activated D-phenylglycine through...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P35/04C07D501/59C07D501/12
CPCC07D501/12C07D501/59C12P35/04
Inventor 韦晓菊莫章桦朱晓媛张辉武
Owner 长沙凯晓生物科技有限公司
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