Method for comprehensively recovering effective ingredients in amoxicillin mother liquid prepared by enzyme process

Abstract

The invention relates to a method for comprehensively recovering effective ingredients in amoxicillin mother liquid prepared by an enzyme process. The method comprises the following steps: (1) concentrating the amoxicillin mother liquid, namely adjusting the pH value of the amoxicillin mother liquid prepared by the enzyme process to be 8.0-9.5, and performing nanofiltration and concentration to obtain concentrated mother liquid; (2) synthesizing amoxicillin under enzyme catalysis, namely adjusting the pH value of the concentrated mother liquid to be 5.8-7.0, and converting 6-APA (6-amino penicillanic acid) and D-methyl hydroxyphenyl glycinate into amoxicillin in the presence of immobilized penicillin acylase for synthesis; (3) preparing D-hydroxyphenyl glycine concentrated liquid by ultrafiltration and nanofiltration, namely separating after the enzyme catalysis reaction is ended to obtain amoxicillin crystals and secondary amoxicillin mother liquid, and performing ultrafiltration and nanofiltration on the secondary mother liquid to obtain the D-hydroxyphenyl glycine concentrated liquid; (4) crystallizing D-hydroxyphenyl glycine. According to the method, 6-APA and D-methyl hydroxyphenyl glycinate remained in the mother liquid are consumed through an indirect process of synthesizing amoxicillin under enzyme catalysis, the product quality of D-hydroxyphenyl glycine is improved, and the yield of D-hydroxyphenyl glycine is increased.

Description

technical field [0001] The invention belongs to the technical field of pharmacy and relates to a method for comprehensively recovering active ingredients in enzymatic amoxicillin mother liquor. Background technique [0002] Amoxicillin (Amoxicillin), also known as amoxycillin or amoxycillin, is one of the most commonly used penicillin-like broad-spectrum β-lactam antibiotics. Amoxicillin has a strong bactericidal effect, has the characteristics of broad spectrum, high efficiency, and low toxicity and side effects, and has been widely used in the field of medicine and health. Its preparations mainly include capsules, tablets, granules, and dispersible tablets. [0003] There are two main methods for synthesizing amoxicillin at present: one is chemical synthesis, and the other is enzymatic synthesis (abbreviated as enzymatic method). The industrial production of amoxicillin began in the 1960s and 1970s. It was traditionally synthesized by chemical synthesis. Due to its mature...

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Problems solved by technology

For example, the enzymatic cleavage process step in the process of extracting and recovering the mother liquor produces a variety of degradation products in the process, and the solution is directly concentrated by nanofiltration, which not only consumes a lot of energy, but also contains complex components in the concentrated solution. 6-APA and D-hydroxyphenylglycine have low efficiency and poor product purity

In addition, in CN102816803A, macroporous adsorption resin is used to process mother liquor, although D-hydroxyphenylglycine and 6-APA are all recovered, but the 6-APA eluate contains a large amount of impurities, which is directly used for amoxicillin synthesis, these Impurities will inevitably accumulate in the product, which will affect the quality and safety of the product. In addition, the use of resin will generate a large amount of waste water, which not only increases the recycling cost of the product, but also has a greater impact on the environment.

And neither of the two patent documents involves the conversion or recovery of D-p-hydroxyphenylglycine methyl ester and amoxicillin in the mother liquor

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