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Method for preparing amoxicillin and phenylacetic acid from benzylpenicillin potassium

A technology for amoxicillin and penicillin potassium, which is applied in the field of preparation of amoxicillin and phenylacetic acid, can solve the problems of unfavorable amoxicillin synthesis yield, impact on amoxicillin product quality, low 6-APA concentration, etc., and achieve colored impurities Less, high yield, high yield effect

Active Publication Date: 2017-03-15
INNER MONGOLIA CHANGSHENG PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The problems in the synthesis of amoxicillin by the straight-through method are: (1) there is phenylacetic acid residue in the 6-APA solution obtained after the lysate is extracted, and phenylacetic acid has an inhibitory effect on amoxicillin synthase
(2) In the process of preparing 6-APA by an enzymatic method, the substrate concentration of the existing immobilized penicillin acylase is low, resulting in a low concentration of 6-APA in the lysate, and finally the 6-APA in the aqueous phase obtained by extraction is low. -The low concentration of APA is not conducive to the improvement of the yield of subsequent amoxicillin synthesis
(3) 6-APA is prepared by the filtrate through a straight-through process, and the extracted aqueous phase contains a certain amount of colored impurities, which will affect the quality of the subsequently synthesized amoxicillin

Method used

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  • Method for preparing amoxicillin and phenylacetic acid from benzylpenicillin potassium
  • Method for preparing amoxicillin and phenylacetic acid from benzylpenicillin potassium
  • Method for preparing amoxicillin and phenylacetic acid from benzylpenicillin potassium

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Embodiment 1

[0047] Embodiment 1 The method for preparing amoxicillin and phenylacetic acid by penicillin potassium according to the present invention

[0048] (1) Penicillin Potassium Cleavage

[0049] Weigh 9kg of penicillin potassium, add 90L of purified water, so that the concentration of penicillin potassium is 10%, then add 10.36kg of penicillin G acylase, the enzyme activity is 155u / g; start stirring, add 3mol / L ammonia water to the feed solution , the pH of the feed liquid was controlled to be 8.1, and the reaction temperature was controlled to be 29° C.; after reacting for 50 minutes, the reaction was stopped, and the feed liquid was separated from the penicillin G acylase to obtain 114 L of lysate, and the concentration of 6-APA was determined to be 45.60 g / L by sampling. The concentration of phenylacetic acid is 28.41g / L, and the cracking yield is 99.48%;

[0050] (2) Extraction

[0051] The lysate obtained in step (1) is cooled down. When the temperature drops to 5° C., add 5...

Embodiment 2

[0080] Embodiment 2 The method for preparing amoxicillin and phenylacetic acid by penicillin potassium according to the present invention

[0081] (1) Penicillin Potassium Cleavage

[0082] Weigh 9kg of penicillin potassium, add 75L of purified water, so that the concentration of penicillin potassium is 12%, then add 10.36kg of penicillin G acylase, the enzyme activity is 155u / g; start stirring, add 3.5mol / L to the feed solution Ammonia water, control the pH of the feed solution to be 8.0, and control the reaction temperature to be 35°C; react for 50 minutes, stop the reaction, separate the feed solution from penicillin G acylase to obtain 100 L of lysate, and take a sample to determine the concentration of 6-APA to be 51.66 g / L , the concentration of phenylacetic acid is 32.57g / L, and the cracking yield is 98.86%;

[0083] (2) Extraction

[0084] The lysate obtained in step (1) is cooled. When the temperature drops to 5° C., add 50 L of dichloromethane to the lysate. The te...

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Abstract

The invention relates to a method for preparing amoxicillin and phenylacetic acid from benzylpenicillin potassium, and belongs to the technical field of pharmaceutics. The method comprises the following steps: splitting benzylpenicillin potassium into 6-APA and phenylacetic acid under the action of penicillin acylase, and extracting the lysate with dichloromethane so as to separate 6-APA from phenylacetic acid; adding ammonia water into the extract water phase, adjusting the pH value of the material liquid to be neutral, removing dichloromethane, performing nanofiltration concentration on the obtained material liquid, and synthesizing amoxicillin from the concentrated liquid with D-p-hydroxybenzene phenylglycine methyl ester under the action of amoxicillin synthetase; and performing alkalization on the dichloromethane phase obtained from extraction of the lysate so as to obtain a sodium phenylacetate solution, and performing oxidation, decoloring, crystallization, suction filtration, washing and drying on the sodium phenylacetate solution, thereby obtaining phenylacetic acid. The lysate contains a relatively small amount of colored impurities, amoxicillin is high in yield and good in product quality, and meanwhile, phenylacetic acid which is qualified in product quality can be recycled and easily applied to production.

Description

technical field [0001] The invention relates to a method for preparing amoxicillin and phenylacetic acid, in particular to a method for preparing amoxicillin and phenylacetic acid from penicillin potassium, and belongs to the technical field of pharmacy. Background technique [0002] There are chemical and enzymatic methods for the synthesis of amoxicillin. Because the chemical method uses a large amount of toxic substances and the reaction conditions are relatively harsh, it has been replaced by the enzymatic method with mild reaction conditions and water phase reaction. The process of enzymatically synthesizing amoxicillin is as follows: 6-APA and D-hydroxyphenylglycine methyl ester synthesize amoxicillin under the action of penicillin G acylase, and the crude amoxicillin obtained is acidified, crystallized, washed and Dry to get amoxicillin. Penicillin potassium is subjected to the action of lyase to obtain a lysate containing 6-APA and phenylacetic acid, and the lysate...

Claims

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Application Information

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IPC IPC(8): C12P7/40C12P37/04C12P37/02C07C51/42C07C51/487C07C57/32
CPCC07C51/42C07C51/487C12P7/40C12P37/04C07C57/32
Inventor 郭建明陈英新眭谦陈顺记王继明韩贺东
Owner INNER MONGOLIA CHANGSHENG PHARMA
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