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A method for controlling the particle size of cefaclor synthesized by biological enzymatic method

A cefaclor and particle size control technology, applied in the field of medicine, can solve the problem of single particle size of cefaclor and unsatisfactory

Active Publication Date: 2020-06-05
苏州盛达药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, cefaclor is an oral antibiotic that can be made into different dosage forms such as tablets, capsules, sustained-release tablets or dry suspensions. Different dosage forms require different particle sizes for cefaclor, and the biological enzyme disclosed in 201310525754.4 In the patent of cefaclor synthetic method, the particle size of cefaclor is relatively single, which cannot meet the requirements of various dosage forms

Method used

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  • A method for controlling the particle size of cefaclor synthesized by biological enzymatic method
  • A method for controlling the particle size of cefaclor synthesized by biological enzymatic method
  • A method for controlling the particle size of cefaclor synthesized by biological enzymatic method

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Effect test

Embodiment 1

[0033] Example 1. Preparation of cefaclor crude product, enzyme reaction mother liquor, and β-naphthol cefaclor complex: according to the method disclosed in the inventor's authorized patent (patent number: CN201310525754.4)

[0034] Put 2.5kg of dissolved 7-ACCA solution and 3.0kg of activated cefaclor immobilized acylase into a 100L enzyme reactor, control the temperature at 12~15℃, and add 2.8kg of D-phenylglycine methyl ester salt Salt water solution, through the automatic pH value control device, the pH value of the enzymatic reaction system is controlled to be constant to 6.5~6.8, and the immobilized enzyme and the cefaclor produced by the reaction are separated every 30 minutes. The separation method is first to separate the enzymatic reaction solution Cross the sieve of 125 microns, obtain filtrate and filtrate after the undersieve is filtered again, filtrate washes filtrate once and then circulates back in the enzyme reactor, collects filtrate and cefaclor crude produc...

Embodiment 2

[0035] Embodiment 2, a kind of biological enzymatic synthesis cefaclor particle size control method

[0036] Take the above 40g β-naphthol cefaclor complex and add it to a 500ml three-necked bottle, add 150ml water and 150ml ethyl acetate, control 10~15°C, add hydrochloric acid with a mass concentration of 15% until dissolved, stir, extract, separate layer, and the aqueous phase was preserved for later use. In another 1000ml three-necked bottle, add 60g of the crude product of cefaclor and 250ml of water, control the temperature at 5~10°C, add dropwise HCL with a mass concentration of 15%, stir to dissolve, pH=0.52, after dissolving, combine the above β-naphthol cefaclor complex extract, add 2g of activated carbon, decolorize for 1 hour, filter, wash with 20ml of water, transfer the filtrate to a 1000ml three-neck flask, add 25ml of methanol, control the temperature at 12~15°C, add dropwise the mass concentration It is a 5% ammonia solution, when the pH=0.85, add seed crystal...

Embodiment 3

[0037] Embodiment 3: A kind of biological enzymatic synthesis cefaclor particle size control method

[0038] Take the above 30g of β-naphthol cefaclor complex and add it to a 500ml three-neck bottle, add 120ml of water and 150ml of ethyl acetate, control the temperature at 5~10°C, add dropwise the HCL solution with a mass concentration of 15% until it dissolves, and stir Extraction, stratification, retain the water phase.

[0039] In another 1000ml three-necked bottle, add 60g of the above-mentioned cefaclor crude product, add 300ml of water, control the temperature at 0~5°C, add dropwise HCL solution with a mass concentration of 35%, stir to dissolve, pH=0.55 to dissolve, and combine the above β- Naphthol cefaclor extract, add 2g of activated carbon to decolorize for 1 hour, filter, wash with 20ml of water, transfer the filtrate to a 1000ml three-necked flask, control the temperature at 10~15°C, add dropwise sodium carbonate solution with a mass concentration of 6%, when the ...

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Abstract

The invention relates to a granularity control method of cefaclor synthesized by a biological enzyme method. The granularity control method comprises the following steps: preparing a cefaclor crude product and an enzyme reaction mother solution; adding beta-naphthol into the enzyme reaction mother solution to obtain a beta-naphthol cefaclor complex; adding ethyl acetate into the beta-naphthol cefaclor complex and adding water or the enzyme reaction mother solution; regulating the pH (Potential of Hydrogen) value to obtain a water phase; adding the water or the enzyme reaction mother solution into the cefaclor crude product and regulating the pH value to obtain a cefaclor crude product solution; after combining the water phase and the cefaclor crude product solution, carrying out de-coloring and filtering; regulating the pH value, carrying out crystallization, filtering, washing and carrying out vacuum drying to obtain the cefaclor. According to the granularity control method provided by the invention, the finished-product cefaclor with the cefaclor granularity key index D90 of 40 microns to 90 microns can be obtained according to requirements, so that the requirements on the granularity by different dosage forms of the cefaclor are met; data of grain diameters which are measured by a granularity meter under different conditions has different size ranges and is normally distributed; the crystal yield can reach 90 percent or more.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for controlling the particle size of cefaclor synthesized by biological enzymatic method. Background technique [0002] Cefaclor is a second-generation oral broad-spectrum cephalosporin antibiotic developed by Eli Lilly and Company in the early 1980s. In recent years, with the continuous advancement of biotechnology, the synthesis of cefaclor by bio-enzyme catalysis technology is becoming more and more mature and gradually replacing the previous chemical synthesis method. Biological enzyme method has the characteristics of lower cost, better quality and environmental friendliness than chemical method synthesis. The cefaclor obtained from the bioenzymatic synthesis of cefaclor is catalyzed and synthesized in the presence of enzymes, and cefaclor is continuously generated and crystallized during the process. Due to the inclusion of enzyme fragments and synthe...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P35/04C07D501/59C07D501/12
Inventor 周自金陈锋罗新祖伍光辉王磊彭尧清韩雪英
Owner 苏州盛达药业有限公司