Process for producing 7-alpha-methoxy-3-deacetyled cefoxitin benzathine

A technology of thiophene benzyl star salt and acetyl head, which is applied in the field of preparation of 7-α-methoxy-3-deacetyl cefotaxime benzyl star salt, and achieves mild reaction conditions, reduced production cost and reduced emission to the environment. Contamination, avoid the effect of low temperature requirements

Inactive Publication Date: 2011-05-25
河北九派制药股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The invention provides a process for producing 7-alpha-methoxy-3-deacetyl cephalothin benzathine salt by immobilized deacetylase participating in the reaction, so as to solve many defects in the existing production process

Method used

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  • Process for producing 7-alpha-methoxy-3-deacetyled cefoxitin benzathine
  • Process for producing 7-alpha-methoxy-3-deacetyled cefoxitin benzathine
  • Process for producing 7-alpha-methoxy-3-deacetyled cefoxitin benzathine

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Effect test

Embodiment 1

[0035] Embodiment 1: As shown in Figure 2, the preparation method of 7-alpha-methoxy-3-deacetyl cephalothin benzathine salt comprises the following steps:

[0036] a. Enzymolysis: Add 100Kg of 7-α-methoxycefalotin cyclohexylamine salt into 500 liters of purified water, stir to dissolve it completely, adjust the pH to 6.5-8.0 with 1N ammonia water, and pour the material into the immobilized After the enzymolysis tank of deacetylase (wherein the immobilized deacetylase is produced by the research institute of Hebei Jiupai Pharmaceutical Co., Ltd., the batch number is: ym080906-160, and the addition amount is 15Kg), control the solution temperature at 20-25°C, Under stirring state, control the pH value at 7.0 to carry out the enzymolysis reaction until the pH does not change within 10 minutes, and when the residual 7-α-methoxycefalotin cyclohexylamine salt is detected by sampling and ≤ 1.0%, the enzymolysis is completed;

[0037] b. Neutralization: after the above-mentioned enzym...

Embodiment 2

[0040] a. Enzyme hydrolysis: Add 100Kg of 7-α-methoxycefalotin cyclohexylamine salt into 1000 liters of purified water, stir to make it completely dissolved, adjust the pH to 6.5-8.0 with 5N sodium carbonate solution, and pour the material into the After the enzymolysis tank of the immobilized deacetylase (wherein the immobilized deacetylase is produced by the Research Institute of Hebei Jiupai Pharmaceutical Co., Ltd., the batch number is ym080906-160, and the addition amount is 50Kg), the temperature of the solution is controlled at 20-25°C, Under stirring, control the pH value at 8.0 to carry out the enzymolysis reaction until the pH does not change within 10 minutes, and when the residual 7-α-methoxycefalotin cyclohexylamine salt is detected by sampling and ≤ 1.0%, the enzymolysis is complete;

[0041] b. Neutralization: After the above-mentioned enzymolysis reaction is completed, put the reacted enzymolysis fluid into the crystallization tank, and then use a small amount o...

Embodiment 3

[0044] a. Enzymolysis: Add 100Kg of 7-α-methoxycefalotin cyclohexylamine salt into 750 liters of purified water, stir to make it completely dissolve, adjust the pH to 6.5-8.0 with 5N sodium carbonate solution, and pour the material into the After the enzymolysis tank of immobilized deacetylase (wherein the immobilized deacetylase is produced by Hebei Jiupai Pharmaceutical Co., Ltd. Research Institute, the batch number is ym080906-160, and the addition amount is 75Kg), control the solution temperature at 20-25°C, Under stirring, control the pH value at 8.0 to carry out the enzymolysis reaction until the pH does not change within 10 minutes, and when the residual 7-α-methoxycefalotin cyclohexylamine salt is detected by sampling and ≤ 1.0%, the enzymolysis is complete;

[0045] b. Neutralization: After the above-mentioned enzymolysis reaction is completed, put the reacted enzymolysis fluid into the crystallization tank, and then use a small amount of 80% acetic acid to adjust the ...

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Abstract

The invention discloses a method for preparing 7-alpha-methoxyl-3-deacetyl cefoxitin benzathine salt by reaction of immobilized deacetylases, which comprises the following steps: adding 7-alpha-methoxyl cefoxitin cyclohexylamine salt into purified water, dissolving the salt, adjusting pH, then carrying out enzymolysis, and adjusting pH of enzymolysis liquor after the enzymolysis is finished; adding ethyl acetate into the neutralized enzymolysis liquor, and adding benzathine diacetate into the solution under stirring; and crystallizing the solution, and then throw-drying and drying the crystalto obtain the product. The method reduces links of decoloring and reduced pressure condensing in the prior art, simplifies operation, reduces consumption, reduces production cost, is convenient for operation, avoids using methanol and sodium hydrate, reduces usage amount of acetic acid, reduces pollution, avoids using liquid nitrogen cold source, and does not need subsequent decoloring process. The material cost of the 7-alpha-methoxyl-3-deacetyl cefoxitin benzathine salt can be reduced by 150 Yuan per kilogram, the production period is shortened to one fourth, and the yield of the product can be improved to 73 percent, so the salt has remarkable social and economic effects, and popularization and application prospects.

Description

technical field [0001] The present invention applies biotechnology to the production process of cefoxitin acid, and is specifically applied to 7-alpha-methoxycefalotin cyclohexylamine salt to 7-alpha-methoxy-3-deacetyl cephalothin benzine Salt reaction process. Background technique [0002] At present, in the production process of cefoxitin acid at home and abroad, the reaction process from 7-α-methoxycefalotin cyclohexylamine salt to 7-α-methoxy-3-deacetyl cephalothin benzine salt is carried out by chemical method . Its specific process route is as shown in Figure 1, and the steps are as follows: [0003] 1. Hydrolysis: add purified water and methanol to the reactor, then cool the contents of the reactor with liquid nitrogen, after cooling to -20~-50°C, add 7-α-methoxycefalotin cyclohexylamine salt and stir Dissolve, then dropwise add sodium hydroxide solution for hydrolysis, continue to cool with liquid nitrogen during hydrolysis to keep the above temperature constant, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P35/00
Inventor 刘秀杰张辑钟建西祁振海刘星邢利锋王亚辉梁建中
Owner 河北九派制药股份有限公司
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