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Method for separating amoxicillin from reaction products of enzymatic preparation of amoxicillin

A technology of amoxicillin and reaction products, which is applied in the field of preparation of amoxicillin, can solve the problems of poor fluidity and low product yield, and achieve the effects of good fluidity, improved product yield, and improved product quality

Inactive Publication Date: 2018-10-23
SHANXI WEIQIDA PHARMA IND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there are still some problems in the practice of enzymatically synthesizing amoxicillin, as the patent CN102660621A provides the process method of 6-APA and D-phenylglycine methyl ester hydrochloride to synthesize amoxicillin, but the final product yield of this method is relatively high low and less fluid

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] This example is used to illustrate the method for separating amoxicillin from the reaction product of enzymatic preparation of amoxicillin provided by the present invention

[0055] (1) Add 70 g of immobilized penicillin acylase, 50 g of 6-APA, 49 g of p-hydroxyphenylglycine methyl ester, and 800 ml of purified water into the enzyme reactor, stir evenly, control the temperature at 20.0° C., and start the reaction. When the pH value stabilized and the 6-APA dropped to 1.0 mg / ml, it was judged that the reaction was over.

[0056] (2) Cool the reaction product to 6°C and separate the enzyme through a 80-mesh sieve. After the separation, wash the enzyme with 150ml of purified water pre-cooled to about 6°C for 3 times, and pass each enzyme washing water through an 80-mesh sieve. net to obtain the enzyme washing solution. Mix the reaction solution and the enzyme washing solution evenly, then transfer it to a dissolution tank, add 3N hydrochloric acid to dissolve it, and cont...

Embodiment 2

[0061] This example is used to illustrate the method for separating amoxicillin from the reaction product of enzymatic preparation of amoxicillin provided by the present invention

[0062] (1) Add 70 g of immobilized penicillin acylase, 50 g of 6-APA, 54 g of p-hydroxyphenylglycine methyl ester hydrochloride, and 800 ml of purified water into the enzyme reactor, stir evenly, control the temperature at 20.0° C., and start the reaction. When the pH value stabilized and the 6-APA dropped to 1.0 mg / ml, it was judged that the reaction was over.

[0063] (2) Cool the reaction product to 3°C, and separate the enzyme through a 80-mesh sieve. After the separation, wash the enzyme with 150ml of purified water pre-cooled to about 3°C ​​for 3 times, and pass each enzyme washing water through an 80-mesh sieve. net to obtain the enzyme washing solution. Mix the reaction solution and the enzyme washing solution evenly, then transfer it to a dissolving tank, add 3N nitric acid to dissolve it...

Embodiment 3

[0068] This example is used to illustrate the method for separating amoxicillin from the reaction product of enzymatic preparation of amoxicillin provided by the present invention

[0069] (1) Add 70 g of immobilized penicillin acylase, 50 g of 6-APA, 49 g of p-hydroxyphenylglycine methyl ester, and 800 ml of purified water into the enzyme reactor, stir evenly, control the temperature at 20.0° C., and start the reaction. When the pH value stabilized and the 6-APA dropped to 1.0 mg / ml, it was judged that the reaction was over.

[0070] (2) Cool the reaction product to 1°C, and separate the enzyme through a 80-mesh sieve. After the separation, wash the enzyme with 150ml of purified water pre-cooled to about 1°C for 3 times, and pass each enzyme washing water through an 80-mesh sieve. net to obtain the enzyme washing solution. Mix the reaction solution and the enzyme washing solution evenly, then transfer it to a dissolving tank, add 6N hydrochloric acid to dissolve it, and cont...

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PUM

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Abstract

The invention relates to the field of amoxicillin preparation, and discloses a method for separating amoxicillin from reaction products of enzymatic preparation of amoxicillin. The method comprises following steps: (1) making reaction products go through a screen with a size of 40-100 meshes at a temperature of 0-10 DEG C to obtain filtrate containing amoxicillin and withheld substances containingenzymes; (2) adjusting the pH of the filtrate to 0.5-2 so as to clarify the solution, then carrying out solid-liquid separation to obtain a liquid phase containing amoxicillin; and (3) adjusting thepH of the liquid phase to 3.5-5.5 by using alkalis to carry out crystallization so as to obtain crystalline slurry containing amoxicillin crystals. The prepared amoxicillin product has a good flowingperformance and the yield is high.

Description

technical field [0001] The invention relates to the field of preparation of amoxicillin, in particular to a method for separating amoxicillin from a reaction product of enzymatic preparation of amoxicillin. Background technique [0002] The chemical name of amoxicillin is (2S,5R,6R)-3,3-dimethyl-6-[(R)-(-)-2-amino-2-(4-hydroxyphenyl)acetamido]- 7-Oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate is one of the most commonly used semi-synthetic penicillin-like broad-spectrum β-lactam antibiotics. [0003] The preparation methods of amoxicillin include chemical synthesis and enzymatic synthesis. The method of chemical synthesis has the disadvantages of long reaction steps, high production of three wastes, and large amount of chemical solvents used in the process. In recent years, with the popularization and application of the concept of green synthesis in the pharmaceutical preparation industry and the development of amoxicillin enzyme synthesis technology, e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D499/68C07D499/18
CPCC07D499/68C07D499/18
Inventor 王启斌田伟陈琪路锐张华秀侯瑞峰刘宏飞
Owner SHANXI WEIQIDA PHARMA IND