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Process for preparing sulbenicillin sodium by using enzymic method

A technology for the preparation of sulbenicillin sodium and enzymatic method, which is applied in the field of enzymatic preparation of sulbenicillin sodium, can solve the problems of high industrial control requirements, high toxicity to operators, cumbersome synthesis process, etc., and achieve environmental pressure relief and safety The effect of high and simplified process

Active Publication Date: 2015-06-10
HUNAN ER KANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] Although the technology of synthesizing sulbenicillin sodium by chemical method is relatively mature at present, there are some common shortcomings, namely, the synthesis process is cumbersome, the industrial control requirements are high, and the toxic organic compounds such as pivaloyl chloride, triethylamine and dichloromethane are used. There are many solvents, which are not only highly toxic to the operators, but also cause great environmental pressure

Method used

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  • Process for preparing sulbenicillin sodium by using enzymic method
  • Process for preparing sulbenicillin sodium by using enzymic method
  • Process for preparing sulbenicillin sodium by using enzymic method

Examples

Experimental program
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Effect test

Embodiment 1

[0034] An enzymatic process for preparing sulfbenicillin sodium includes the following steps:

[0035] (1) Add 100L of 10% penicillin fermentation broth to a reactor equipped with 2000KU penicillin acylase, adjust the pH of the solution to about 8.3 with 5% ammonia water, set the temperature to 35°C, and stir at 750 rpm. During the reaction, the content of penicillin is detected. When the conversion rate of penicillin is ≥95%, pass the resulting mixture through the screen at the bottom of the reactor to trap penicillin acylase and other macromolecular substances;

[0036] (2) Pass the mixed solution obtained in step (1) through an ultrafilter with a molecular weight cut-off of 3000-5000 Dalton and a nanofilter with a molecular weight cut-off of 100-200 Dalton to obtain a concentrated solution;

[0037] (3) Decolorize the concentrated solution obtained in step (2) with activated carbon. The amount of activated carbon added is 2.5‰, and the phenylacetic acid is adsorbed and se...

Embodiment 2

[0041] An enzymatic process for preparing sulfbenicillin sodium includes the following steps:

[0042] (1) Add 100L of 10% penicillin fermentation broth to the reactor equipped with 2000KU penicillin acylase, adjust the pH of the solution to about 7.8 with 5% ammonia water, set the temperature to 25°C, and stir at 600 rpm. During the reaction, the content of penicillin is detected. When the conversion rate of penicillin is ≥95%, pass the resulting mixture through the screen at the bottom of the reactor to trap penicillin acylase and other macromolecular substances;

[0043] (2) Pass the mixed solution obtained in step (1) through an ultrafilter with a molecular weight cut-off of 3000-5000 Dalton and a nanofilter with a molecular weight cut-off of 100-200 Dalton to obtain a concentrated solution;

[0044] (3) Decolorize the concentrated solution obtained in step (2) with activated carbon. The added amount of activated carbon is 5‰, and the phenylacetic acid is adsorbed and se...

Embodiment 3

[0048] An enzymatic process for preparing sulfbenicillin sodium includes the following steps:

[0049] (1) Add 10% penicillin fermentation broth to a reactor equipped with 2000KU penicillin acylase, adjust the pH of the solution to about 8.5 with 5% ammonia, set the temperature to 28°C, and stir at 700 revolutions per minute. During the process, the content of penicillin is detected. When the conversion rate of penicillin is ≥95%, the resulting mixture is passed through the screen at the bottom of the reactor to trap penicillin acylase and other macromolecular substances;

[0050] (2) Pass the mixed solution obtained in step (1) through an ultrafilter with a molecular weight cut-off of 3000-5000 Dalton and a nanofilter with a molecular weight cut-off of 100-200 Dalton to obtain a concentrated solution;

[0051] (3) Decolorize the concentrated solution obtained in step (2) with activated carbon. The amount of activated carbon added is 6‰, and the phenylacetic acid is adsorbed...

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Abstract

The invention discloses a process for preparing sulbenicillin sodium by using an enzymic method, and belongs to the technical field of medicines and chemical engineering. The method comprises a step that by omitting the steps of crystallizing, washing and drying 6-aminopenicillanicacid, direct reaction on penicillin fermentation liquid used as an initial raw material and phenylacetyl chloride is carried out under a function of penicillin acylase to obtain sulbenicillin sodium. Compared with a chemical synthetic method, the preparation process provided by the invention is easy to operate, small in energy consumption, high in security and high in stability; therefore, the process is a production process with low cost and high efficiency in popularization and application of industrial production.

Description

Technical field [0001] The invention relates to a process for preparing sulbenicillin sodium by an enzymatic method, and belongs to the technical field of medicine and chemical industry. Background technique [0002] Sulbenicillin sodium, the Chinese chemical name is (2S,5R,6R)-3,3-dimethyl-6-(2-phenyl-2-sulfoacetamido)-7-oxo-4-thia -1-Azabicyclo[3.2.0]heptane-2-carboxylic acid disodium salt; generally white or light yellow powder; very soluble in water, soluble in methanol, and slightly soluble in ethanol. [0003] Sulbenicillin sodium is a broad-spectrum semi-synthetic anti-pseudomonas penicillin, and its antibacterial spectrum is similar to carbenicillin. Its mechanism of action is to produce antibacterial effects by interfering with the synthesis of bacterial cell walls. It is mainly suitable for Pseudomonas aeruginosa, certain Proteobacteria, Staphylococcus, Streptococcus and other gram-positive bacteria that are sensitive to this product. It has good antibacterial activit...

Claims

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Application Information

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IPC IPC(8): C12P37/04C12P37/02
Inventor 帅放文王向峰章家伟
Owner HUNAN ER KANG PHARMA
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