Method for enzymatic synthesis of penicillin V salt

A technology of penicillin V and enzymatic synthesis, which is applied in the field of medicine and chemical industry to achieve the effects of good product quality, low cost and short production cycle

Active Publication Date: 2019-04-16
HUNAN FLAG BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with the fermentation method, the enzymatic synthesis method has the advantages of short production cycle, simple process, mild reaction

Method used

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  • Method for enzymatic synthesis of penicillin V salt
  • Method for enzymatic synthesis of penicillin V salt
  • Method for enzymatic synthesis of penicillin V salt

Examples

Experimental program
Comparison scheme
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Example Embodiment

[0031] Example 1

[0032] Take 25.0g 6-APA, add 300mL pure water, drop 3mol / L ammonia solution to fully dissolve 6-APA, add 30.0g phenoxyglycol acetate, mix well, add 50.0g immobilized penicillin acylase , 3mol / L ammonia solution was added dropwise to make the reaction pH 5.0, the temperature was 30°C, and the reaction time was 90 minutes for sampling and HPLC detection. At this time, the concentration of 6-APA was 0.8 mg / mL and the concentration of penicillin V was 106.9 mg / mL; Separate the immobilized enzyme and the reaction solution, adjust the pH value of the reaction solution to 3.0 with 6mol / L hydrochloric acid, grow the crystals for 20 minutes, and filter to obtain a penicillin V acid filter cake; the filter cake is transferred to 5 times the weight of pure water and used Adjust the pH value of the mixed solution with a certain concentration of potassium carbonate solution to 6.0, then add n-butanol to a certain concentration, and concentrate by evaporation under reduced p...

Example Embodiment

[0033] Example 2

[0034] Take 25.0g of 6-APA, add 400mL of pure water, add 3mol / L ammonia solution dropwise to fully dissolve 6-APA, add 30.0g of phenoxyglycerol, mix well, add 75.0g of immobilized penicillin acylase, dropwise Add 3mol / L ammonia solution to make the reaction pH 6.0, temperature 20°C, and react for 80 minutes to sample by HPLC. At this time, the concentration of 6-APA is 0.3 mg / mL, and the concentration of penicillin V is 87.5 mg / mL; the screen is separated and fixed. Chemical enzyme and reaction solution, adjust the pH value of the reaction solution to 2.8 with 6mol / L hydrochloric acid, grow crystals for 20 minutes, and filter to obtain penicillin V acid filter cake; the filter cake is transferred to 4 times the weight of pure water with a certain concentration Adjust the pH value of the mixed solution to 6.3 with potassium carbonate solution, then add n-butanol to a certain concentration, and concentrate by evaporation under reduced pressure until crystals are ...

Example Embodiment

[0035] Example 3

[0036] Take 25.0g 6-APA, add 400mL pure water, drop 3mol / L ammonia solution to fully dissolve 6-APA, add 35.0g phenoxybutyl erythritol, mix well, add 50.0g immobilized penicillin acylase , 3mol / L ammonia solution was added dropwise to make the reaction pH 5.0, temperature 30°C, reaction for 90 minutes, sampling HPLC detection, at this time 6-APA concentration is 0.5mg / mL, penicillin V concentration is 89.0mg / mL; Separate the immobilized enzyme from the reaction solution, adjust the pH value of the reaction solution to 2.8 with 6mol / L hydrochloric acid, grow the crystals for 20 minutes, and filter to obtain a penicillin V acid filter cake; the filter cake is transferred to 4 times the weight of pure water and used Adjust the pH value of the mixed solution with a certain concentration of potassium carbonate solution to 6.5, then add n-butanol to a certain concentration, and concentrate by evaporation under reduced pressure until crystals are precipitated. The cry...

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Abstract

The invention discloses a method for enzymatic synthesis of penicillin V salt. The method comprises the steps of enzymatically catalyzing the reaction of 6-APA and a phenoxyacetic acid derivative anda penicillin acylase catalyst to generate penicillin V; acidizing and dissolving out a penicillin V crystal after acylation enzyme in the solution is separated, and salting the penicillin V crystal toobtain the penicillin V salt. Compared with the prior art, the production period of the method is short, the method is simple in operation, friendly to the environment, free of pollution and low in production cost, the liquid phase purity of the prepared penicillin V salt can reach 99.7% or above, 4-hydroxyphenoxymethyl penicillin (impurity D) is not detected out, the polymer impurity is less than 0.02%, the product quality far exceeds the quality of the penicillin V salt produced by an existing fermentation method and is higher than the quality standards of similar foreign drug materials, and the method has a good industrial application value.

Description

technical field [0001] The invention relates to a method for synthesizing penicillin V salt, in particular to a method for generating penicillin V by reacting 6-APA and phenoxyacetic acid derivative raw materials in the next step under the catalysis of penicillin acylase, and belongs to the technical field of medicine and chemical industry. Background technique [0002] Penicillin V salts (penicillin V potassium, penicillin V sodium) are clinically commonly used antibiotics, and penicillin V potassium is more widely used. Penicillin V Potassium is a β-lactamase antibiotic. Its antibacterial spectrum is similar to that of penicillin G. It can destroy bacterial cell walls and has bactericidal effect. Abscess, purulent meningitis, pneumonia, gonorrhea embolism. Compared with penicillin G potassium / sodium, penicillin V potassium is stable to acid, not easy to be destroyed by gastric acid, and has good oral absorption, and its oral preparation is especially suitable for children...

Claims

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Application Information

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IPC IPC(8): C12P37/04
CPCC12P37/04
Inventor 许岗张娇黄斌苏程举曾红宇赵士敏
Owner HUNAN FLAG BIOTECHNOLOGY CO LTD
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