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Process for enzymatic synthesis of cefprozil

A technology of enzymatic synthesis of cefprozil, which is applied to the direction of immobilized on/in organic carrier, fermentation, etc., can solve the problems of difficult screening and evaluation of immobilized enzymes, cumbersome production process steps, long reaction time, etc. The effect of shortened time, good product quality and short reaction time

Inactive Publication Date: 2015-09-23
AMICOGEN CHINA BIOPHARM CO LTD
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Problems solved by technology

[0005] Aiming at the problems in the existing enzymatic synthesis process of cefprozil, the screening and evaluation of immobilized enzymes is difficult, the production process steps are cumbersome, the control points are poor, the reaction time is long, the conversion rate is low, etc., the invention provides an immobilized cefprozil synthase , and a new process for the synthesis of cefprozil

Method used

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  • Process for enzymatic synthesis of cefprozil
  • Process for enzymatic synthesis of cefprozil

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Experimental program
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Effect test

Embodiment 1

[0034] In the reactor, 3900 u of immobilized cefprozil synthase was added to 130 mL of deionized water, and the stirring was started. 0.04 mol of 7-APRA and 0.046 mol of D-p-hydroxyphenylglycine methyl ester were added. Sodium hydroxide was added to adjust the reaction pH to 6.8. The reaction temperature was maintained at 19-20°C. React for 100min. The reaction solution was separated from the immobilized cefprozil synthetase. The obtained product is adjusted to pH 1.1-1.2 with 30% hydrochloric acid, dissolved, filtered, and then adjusted to pH with 20% ammonia solution to crystallize, and the final pH is 5.0-5.2. After growing the crystal at 0-5°C for 1 hour, washing and drying, the finished product of cefprozil was obtained.

Embodiment 2

[0036] In the reactor, 2600 u of immobilized cefprozil synthase was added to 130 mL of deionized water, and the stirring was started. 0.04 mol of 7-APRA and 0.048 mol of D-p-hydroxyphenylglycine methyl ester hydrochloride were added. Sodium hydroxide was added to adjust the reaction pH to 7.0. The reaction temperature was maintained at 14-15°C. React for 120min. The reaction solution was separated from the immobilized cefprozil synthetase. The obtained product is adjusted to pH 1.1-1.2 with 30% hydrochloric acid, dissolved, filtered, and then adjusted to pH with 20% ammonia solution to crystallize, and the final pH is 5.0-5.2. After growing the crystal at 0-5°C for 1 hour, washing and drying, the finished product of cefprozil was obtained.

Embodiment 3

[0038] In the reactor, 3000 u of immobilized cefprozil synthase was added to 130 mL of deionized water, and the stirring was started. 0.04 mol of 7-APRA and 0.044 mol of D-p-hydroxyphenylglycine methyl ester were added. Sodium hydroxide was added to adjust the reaction pH to 7.1. The reaction temperature was maintained at 10-11°C. React for 120min. The reaction solution was separated from the immobilized cefprozil synthetase. The obtained product is adjusted to pH 1.1-1.2 with 30% hydrochloric acid, dissolved, filtered, and then adjusted to pH with 20% ammonia solution to crystallize, and the final pH is 5.0-5.2. After growing the crystal at 0-5°C for 1 hour, washing and drying, the finished product of cefprozil was obtained.

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Abstract

The invention relates to a medicine synthesis method, in particular to a process method for screening of immobilized cefprozil synthetase and enzymatic synthesis of cefprozil. In order to solve the problems that a conventional cefprozil enzymatic synthesis process has difficulties in screening and evaluating immobilized anzyme, tedious in production process step, poor in control point, long in reaction time, low in conversion ratio and the like, the invention provides an immobilized cefprozil synthetase and a novel process for cefprozil synthesis.

Description

technical field [0001] The invention relates to a method for synthesizing medicines, in particular to screening of immobilized cefprozil synthase and a process for enzymatically synthesizing cefprozil. Background technique [0002] Cefprozil is a second-generation broad-spectrum cephalosporin antimicrobial drug against G + , G - Bacteria and anaerobic bacteria have strong antibacterial activity, against G + Bacterial activity is particularly prominent. Cefprozil is safe and has very few adverse reactions. Approved by the FDA in December 1991, it is clinically used for mild and moderate infections caused by sensitive bacteria, including upper and lower respiratory tract infections, as well as skin and skin and soft tissue infections. [0003] In recent years, the enzymatic synthesis of cefprozil has become the focus of research. Compared with chemical methods, enzymatic methods have obvious advantages in terms of environmental protection and cost. The process for prepar...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P35/04C12N11/08
Inventor 林炳旺乔浩赵康王玲李建国方军商爱国
Owner AMICOGEN CHINA BIOPHARM CO LTD
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