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
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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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