Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for synthesizing amoxicillin and generating byproduct of sodium phenylacetate solution by using semi-direct method

A technology of amoxicillin and sodium phenylacetate, which is applied in chemical instruments and methods, preparation of organic compounds, preparation of carboxylate, etc., can solve the problems of phenylacetic acid residue, low 6-APA concentration and low substrate concentration, etc. To achieve the effect of eliminating the generation of waste water, reducing production costs and improving product quality

Inactive Publication Date: 2018-05-04
INNER MONGOLIA CHANGSHENG PHARMA
View PDF4 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The above-mentioned patent has developed a method for the synthesis of amoxicillin by the straight-through method, but there are the following deficiencies: (1) the penicillin lysate is directly concentrated by nanofiltration without separating phenylacetic acid and 6-APA. phenomenon, so it is necessary to use high-pressure nanofiltration, and the use of high-pressure nanofiltration increases the energy consumption of the treatment process
(2) Lysis solution is directly acidified, so that phenylacetic acid and other impurities in the lysis solution are separated out simultaneously, which is unfavorable to the product quality of phenylacetic acid
At the same time, the above-mentioned patents do not effectively recover phenylacetic acid in the lysate
[0005] In addition to the deficiencies of the above-mentioned patent straight-through method for synthesizing amoxicillin, the problems of the straight-through method for synthesizing amoxicillin include: (1) there is phenylacetic acid residue in the 6-APA solution obtained after the lysate is extracted, and phenylacetic acid has no effect on amoxicillin. synthetase inhibitory
(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

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for synthesizing amoxicillin and generating byproduct of sodium phenylacetate solution by using semi-direct method
  • Method for synthesizing amoxicillin and generating byproduct of sodium phenylacetate solution by using semi-direct method
  • Method for synthesizing amoxicillin and generating byproduct of sodium phenylacetate solution by using semi-direct method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1 A kind of semi-straight-through method of the present invention synthesizes the method for amoxicillin and by-product sodium phenylacetate solution

[0038] (1) Penicillin Potassium Cleavage

[0039] Weigh 9kg of penicillin potassium, add 91L of purified water, so that the concentration of penicillin potassium is 9%, then add 10.55kg of penicillin G acylase, the enzyme activity is 150u / g; start stirring, add 3mol / L ammonia water to the feed solution , control the pH of the feed solution to be 8.1-8.2, and control the reaction temperature to be 28-30°C; react for 53 minutes, stop the reaction, separate the feed solution from penicillin G acylase to obtain 116L of lysate, and take a sample to determine the concentration of 6-APA to be 44.69 g / L, the concentration of phenylacetic acid is 27.71g / L, the cracking yield is 99.20%, and the lysate is obtained;

[0040] (2) Extraction

[0041] The lysate obtained in step (1) is cooled. When the temperature drops to...

Embodiment 2

[0060] Embodiment 2 A kind of semi-straight-through synthesis method of amoxicillin and by-product sodium phenylacetate solution according to the present invention

[0061] (1) Penicillin Potassium Cleavage

[0062] Weigh 9kg of penicillin potassium, add 66L of purified water, so that the concentration of penicillin potassium is 12%, then add 10.21kg of penicillin G acylase, the enzyme activity is 155u / g; start stirring, add 3mol / L ammonia water to the feed solution , control the pH of the feed solution to be 8.1-8.2, and control the reaction temperature to be 28-30°C; react for 45 minutes, stop the reaction, separate the feed solution from penicillin G acylase to obtain 88L of lysate, and take a sample to determine the concentration of 6-APA to be 58.41 g / L, the concentration of phenylacetic acid is 35.63g / L, and the cleavage yield is 98.36%, and the lysate is obtained;

[0063] (2) Extraction

[0064] The lysate obtained in step (1) was cooled down. When the temperature dr...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
concentrationaaaaaaaaaa
concentrationaaaaaaaaaa
Login to View More

Abstract

The invention relates to a method for synthesizing amoxicillin and generating a byproduct of a sodium phenylacetate solution by using a semi-direct method and belongs to the technical field of medicine preparation. The method comprises the following steps: splitting benzylpenicillin potassium into 6-APA (Amino Penicillanic Acid) and phenylacetic acid under the action of penicillin acylase, extracting a splitting solution with dichloromethane to separate 6-APA from the phenylacetic acid, putting ammonia water into an extraction water phase, adjusting the pH value of a material liquid to be neutral, removing the dichloromethane, putting the solid 6-APA into the obtained 6-APA dissolving liquid, and synthesizing the amoxicillin together with D-methyl p-hydroxyphenylglycinate under the actionof amoxicillin synthetase. A sodium phenylacetate solution can be prepared by alkalizing the dichloromethane obtained by extracting the splitting solution, the sodium phenylacetate solution can be directly applied to fermentation production of penicillin, the step of recycling the phenylacetic acid is avoided, and the production cost is reduced.

Description

technical field [0001] The invention relates to a method for synthesizing amoxicillin and by-product sodium phenylacetate solution by a semi-straight-through method, belonging 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 is extracted, crystallized, washed and dri...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C12P37/04C12P7/40C07C57/32C07C51/41
CPCC07C51/412C12P7/40C12P37/04C07C57/32
Inventor 陈顺记郭军臣郭建明刘钊张鸿宾韩贺东周颖
Owner INNER MONGOLIA CHANGSHENG PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com