Process for direct preparation of amoxicillin by liquid 6-APA (amino penicillanic acid)

A technology of 6-APA and amoxicillin, which is applied in the field of drug preparation, can solve problems such as not being suitable for expanding production, increasing 6-APA degradation, and affecting yield, so as to improve drug safety, reduce investment, Effect of reducing energy loss

Active Publication Date: 2016-06-08
INNER MONGOLIA CHANGSHENG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The process of resin column chromatography in the patent to treat the lysate is complicated. On the one hand, it is not suitable for expan

Method used

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  • Process for direct preparation of amoxicillin by liquid 6-APA (amino penicillanic acid)
  • Process for direct preparation of amoxicillin by liquid 6-APA (amino penicillanic acid)
  • Process for direct preparation of amoxicillin by liquid 6-APA (amino penicillanic acid)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Liquid 6-APA straight-through amoxicillin

[0023] (1) in the reactor that immobilized penicillin G acylase (I type) 1kg is housed, add penicillin concentration and be 20kg of penicillin degreasing liquid of 10wt%, control cleavage reaction pH to be 8.0, temperature 30 ± 1 ℃, when pH has no When fluctuating, detect the content of penicillin, calculate when the conversion rate of penicillin is 98.8%, discharge, obtain the mixed cracking solution of 6-APA and phenylacetic acid;

[0024] (2) Add 50% dichloromethane of the volume of the lysate to the lysate, and adjust the pH value to 1.0 with 30wt% hydrochloric acid, stir, leave to separate phases, and separate to obtain an aqueous phase containing 6-APA;

[0025] (3) Chromatographically separate the aqueous phase through a LXT-080 macroporous adsorption resin column, control the flow rate to 4BV / h, and the temperature at 5-10°C. After passing through the resin column, it is detected that the residual phenylaceti...

Embodiment 2

[0029] Example 2 Liquid 6-APA straight-through amoxicillin

[0030] (1) in the reactor that immobilized penicillin G acylase (I type) 2.4kg is housed, add penicillin concentration and be 15wt% penicillin degreasing liquid 20kg, control cleavage reaction pH to be 7.8, temperature 28 ± 1 ℃, when pH When there is no fluctuation, the content of penicillin is detected, and when the conversion rate of penicillin is calculated to be 98.2%, the material is discharged to obtain a mixed lysis solution of 6-APA and phenylacetic acid;

[0031] (2) Add dichloromethane with 100% volume of the lysate to the lysate, and adjust the pH value to 1.0 with 30wt% hydrochloric acid, stir, leave to separate phases, and separate to obtain an aqueous phase containing 6-APA;

[0032] (3) Chromatographically separate the aqueous phase through a LXT-080 macroporous adsorption resin column, control the flow rate to 3BV / h, and the temperature at 5-10°C. After passing through the resin column, it is detected...

Embodiment 3

[0036] Example 3 Liquid 6-APA straight-through amoxicillin

[0037] (1) in the reactor that immobilized penicillin G acylase (I type) 22kg is housed, adding penicillin concentration is 20kg of penicillin degreasing liquid of 18wt%, and the control cleavage reaction pH is 8.2, and temperature 32 ± 1 ℃, when pH has no When fluctuating, detect the content of penicillin, calculate when the conversion rate of penicillin is 98.3%, discharge, obtain the mixed lysis solution of 6-APA and phenylacetic acid;

[0038] (2) Add dichloromethane of 1 / 3 of the volume of the lysate to the lysate, and adjust the pH value to 1.0 with 30wt% hydrochloric acid, stir, stand still and separate phases, and separate to obtain an aqueous phase containing 6-APA;

[0039](3) Chromatographically separate the aqueous phase through a LXT-081 macroporous adsorption resin column, control the flow rate to 5BV / h, and the temperature at 5-10°C. After passing through the resin column, it is detected that the resid...

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Abstract

The invention belongs to the technical field of medicine preparation and relates to a process for direct preparation of amoxicillin by liquid 6-APA (amino penicillanic acid). The process includes: taking penicillin degreasing solution as an initial material, sequentially performing cracking reaction, extraction, phase splitting, resin column adsorptive purification, distillation and concentration to obtain a 6-APA solution with the concentration being 80-100g/L, and synthesizing with p-hydroxyphenylglycine methyl ester under a catalytic action of type-II penicillin G acylase to obtain the amoxicillin. Compared with a traditional method, the process has the advantages that subsequent steps of 6-APA crystallization, centrifuging, drying and the like are avoided, investment of fixed assets is reduced, energy loss, equipment loss and cost are reduced, profits are increased, and physical injuries of staffs are reduced. Compared with existing direct amoxicillin preparation methods, the process has the advantages that by adoption of dichloromethane as an extracting agent, total mole yield of amoxicillin is higher relatively, the extracting agent is easy for distillation separation, the content of residual solvents in products is greatly reduced, medication safety is improved, and the process is worthy of popularization in production.

Description

technical field [0001] The invention relates to a process for preparing amoxicillin, in particular to a process for directly preparing amoxicillin with liquid 6-APA, and belongs to the technical field of medicine preparation. Background technique [0002] Amoxicillin, also known as amoxycillin, is the most commonly used semi-synthetic penicillin broad-spectrum β-lactam antibiotics. It has strong bactericidal effect and strong ability to penetrate cell membranes. One of the synthetic penicillins. [0003] At present, the vast majority of domestic antibiotic pharmaceutical companies use bio-enzymatic methods to synthesize amoxicillin. The main process is: p-Hydroxyphenylglycine methyl ester and solid 6-APA synthesize amoxicillin under the action of penicillin G acylase. The high cost of solid 6-APA used in this process is a major problem faced by amoxicillin pharmaceutical companies at present. In recent years, some pharmaceutical companies have developed a liquid 6-APA stra...

Claims

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Application Information

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IPC IPC(8): C12P37/04C07D499/18C07D499/68
CPCC07D499/18C07D499/68C12P37/04
Inventor 陈顺记陈英新眭谦韩贺东郭建明王继明吴小军郭明茜姚东娟
Owner INNER MONGOLIA CHANGSHENG PHARMA
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