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A kind of technology that enzymatic method prepares sulbenicillin sodium

A technology for preparing sulfobenicillin sodium and an enzymatic method is applied in the field of preparing sulfobenicillin sodium by an enzymatic method, which can solve the problems of high industrial control requirements, high toxicity to operators, cumbersome synthesis process, etc., and achieves alleviation of environmental pressure and safety. High and simplified process effect

Active Publication Date: 2017-08-29
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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  • A kind of technology that enzymatic method prepares sulbenicillin sodium
  • A kind of technology that enzymatic method prepares sulbenicillin sodium
  • A kind of technology that enzymatic method prepares sulbenicillin sodium

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Effect test

Embodiment 1

[0034] A kind of technique that enzymatic method prepares sulbenicillin sodium comprises the following steps:

[0035] (1) Add 100L of 10% penicillin fermentation broth to the 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 the stirring speed to 750 rpm, Detect the content of penicillin during the reaction, and when the conversion rate of penicillin is ≥ 95%, pass the resulting mixture through the screen at the bottom of the reactor to intercept penicillin acylase and other macromolecular substances;

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

[0037] (3) The concentrated solution obtained in step (2) was decolorized with activated carbon, the amount of activated carbon added was 2...

Embodiment 2

[0041] A kind of technique that enzymatic method prepares sulbenicillin sodium comprises 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 the stirring speed to 600 rpm, Detect the content of penicillin during the reaction, and when the conversion rate of penicillin is ≥ 95%, pass the resulting mixture through the screen at the bottom of the reactor to intercept penicillin acylase and other macromolecular substances;

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

[0044] (3) The concentrated solution obtained in step (2) was decolorized with activated carbon, the amount of activated carbon added was 5...

Embodiment 3

[0048] A kind of technique that enzymatic method prepares sulbenicillin sodium comprises 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 water, set the temperature to 28°C, and stir at 700 rpm. Detect the content of penicillin during the process. When the conversion rate of penicillin is ≥ 95%, pass the resulting mixture through the screen at the bottom of the reactor to intercept penicillin acylase and other macromolecular substances;

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

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

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Abstract

The invention discloses a process for preparing sulfbenicillin sodium by enzymatic method, which belongs to the technical field of medicine and chemical industry. The method uses penicillin fermented liquid as a starting material, omits the steps of 6-aminopenicillanic acid crystallization, washing and drying, and directly reacts with sulfophenylacetyl chloride under the action of penicillin acylase to obtain sulfbenicillin sodium. Compared with the chemical synthesis method, the preparation process provided by the invention is simple in operation, low in energy consumption, high in safety and good in stability. Therefore, the present invention is a low-cost, high-efficiency production process in the popularization and application of industrial production.

Description

technical field [0001] The invention relates to a process for preparing sulfbenicillin sodium by enzymatic method, which 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, easily soluble in methanol, slightly soluble in ethanol. [0003] Sulbenicillin sodium is a broad-spectrum semi-synthetic antipseudomonal penicillin with a similar antibacterial spectrum to carbenicillin. Its mechanism of action is to produce antibacterial effect by interfering with the synthesis of bacterial cell wall. It is mainly suitable for Gram-positive bacteria such as Pseudomonas aeruginosa, certain Proteus, Staphylococcus, and Streptococcus that are sensitive to this product, and has good antibacterial activity. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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