Technology for preparing amoxicillin by straight-through method

A technology of amoxicillin and straight-through method, applied in the pharmaceutical field, can solve the problems of affecting the health of production personnel, 6-APA is prone to flying, and the labor intensity of production personnel is high, so as to strengthen the health protection of employees, reduce the allergy rate, reduce the The effect of energy consumption

Active Publication Date: 2014-10-15
石药集团中诺药业(石家庄)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This process uses solid 6-APA as the reaction raw material, that is to say, the final reaction solution for preparing 6-APA in the existing enzymatic process cannot be directly used for the preparation of amoxicillin, and it needs crystallization, suction filtration, After a series of treatments such as washing and drying, the 6-APA solid can be used for the preparation of amoxicillin. The operation steps are cumbersome, and the labor intensity of the production personnel is high, and the dried 6-APA is prone to flying, which is easy to cause allergies and affects the production personnel. good health

Method used

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  • Technology for preparing amoxicillin by straight-through method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment 1 straight-through method prepares amoxicillin

[0030]a. Take 20L of penicillin degreasing solution with a penicillin concentration of 6%, add it to a reactor equipped with 200KU penicillin acylase, control the pH value to 8.0, control the reaction temperature to 28±1°C, and detect the content of penicillin during the reaction , calculate the conversion rate of penicillin, when the result is 97.4%, release the feed liquid, intercept the penicillin acylase by the screen mesh at the bottom of the reactor, transfer the obtained filtrate to the nanofiltration system with a membrane molecular weight of 120nm for concentration, and obtain a concentration of 70g / L 6-APA solution;

[0031] b. Add 18% hydrochloric acid aqueous solution to the 6-APA solution obtained in step a, adjust the pH value to 1.0, then add 50% butanol by volume of the 6-APA solution for extraction, and separate the aqueous phase;

[0032] c. Take the aqueous phase obtained in step b and pass ...

Embodiment 2

[0035] Embodiment 2 straight-through method prepares amoxicillin

[0036] a. Take 20L of penicillin degreasing solution with a penicillin concentration of 10%, add it to a reactor equipped with 200KU penicillin acylase, control the pH value to 8.5, control the reaction temperature to 37±1°C, and detect the content of penicillin during the reaction , calculate the conversion rate of penicillin, when the result is 98.1%, discharge feed liquid, intercept penicillin acylase by screen cloth at the bottom of the reactor, transfer the gained filtrate to the nanofiltration system and concentrate, and obtain concentration is 120g / L 6- APA solution;

[0037] b. Add 30% hydrochloric acid aqueous solution to the 6-APA solution obtained in step a, adjust the pH value to 2.0, then add 70% butyl ester of 6-APA solution volume for extraction, and separate the aqueous phase;

[0038] c. Take the aqueous phase obtained in step b and pass it through the LXT-057 macroporous resin column, control...

Embodiment 3

[0041] Embodiment 3 straight-through method prepares amoxicillin

[0042] a. Take 20L of penicillin degreasing solution with a penicillin concentration of 8%, add it to a reactor equipped with 200KU penicillin acylase, control the pH value to 8.2, control the reaction temperature to 32±1°C, and detect the content of penicillin during the reaction , calculate the transformation rate of penicillin, when the result is 97.8%, discharge feed liquid, intercept penicillin acylase by screen cloth at the bottom of the reactor, transfer the gained filtrate to the nanofiltration system and concentrate, and obtain concentration is 100g / L 6- APA solution;

[0043] b. add 25% hydrochloric acid aqueous solution in the 6-APA solution that step a obtains, adjust pH value to be 1.5, then add the butanol butyl ester mixture of 6-APA solution volume 60% (the volume ratio of butanol and butyl ester is 2:3) extract and separate the aqueous phase;

[0044] c. Take the aqueous phase obtained in ste...

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Abstract

The invention discloses a technology for preparing amoxicillin by a straight-through method. The technology takes a penicillin degreasing fluid as a starting raw material; 6-APA (6-amino penicillanic acid) crystallization, suction filtration, washing and drying steps are saved; the amoxicillin can be prepared without obtaining solid 6-APA via separation; and the prepared amoxicillin meets a requirement of a medicinal standard. The technology saves an operation procedure, reduces the labor intensity of production personnel, lowers the production cost, reduces environmental protection pressure, avoids contact between the production personnel and 6-APA dry powder, and reduces anaphylaxis.

Description

technical field [0001] The invention belongs to the technical field of pharmacy, and in particular relates to a preparation process of amoxicillin. Background technique [0002] Amoxicillin (Amoxicillin) is a β-lactam antibiotic and is currently the most widely used oral antibiotic species, with an annual global consumption of more than 15,000 tons. [0003] At present, there are two processes for the synthesis of amoxicillin: chemical method and enzymatic method. The chemical method is widely used, and its technological process is as follows: after mixing p-hydroxyphenylglycine Deng potassium salt and pivaloyl chloride, amoxicillin is synthesized through processes such as mixed anhydride, condensation, hydrolysis, and crystallization. This process route is long and uses a large amount of special More toxic substances such as valeryl chloride, pyridine, triethylamine and methylene chloride are not only highly toxic to operators, but also cause great pollution to the environ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P37/04
Inventor 朱科刘健陈英新徐永龙马文婵王士科鲍建芝梅玉龙靳献蕊李银
Owner 石药集团中诺药业(石家庄)有限公司
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