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Method for preparing amoxicillin or ampicillin through full water phase

A technology of amoxicillin and ampicillin, applied in the direction of fermentation, etc., can solve the problems of environmental pollution, low environmental pollution, low production capacity, etc., and achieve the effects of simplified process steps, high activity coefficient, and strong adaptability to the environment

Active Publication Date: 2019-01-15
HUNAN FLAG BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In the existing methods for synthesizing amoxicillin or ampicillin, there is a low cracking concentration of penicillin GK, phenylacetic acid in 6-APA cannot be removed by chemical methods or resins, and phenylacetic acid inhibits the synthesis reaction of amoxicillin, so it is used in the process A large amount of organic solvents lead to low production capacity, high production cost, serious environmental pollution and a series of problems. The purpose of the present invention is to provide a cracking of penicillin GK (VK) at a high concentration, and can realize 6 in the cracking product. -Complete separation of APA, high-yield preparation method of high-purity amoxicillin or ampicillin, this method does not use organic solvents in the whole process, has little environmental pollution, low cost, and meets the requirements of industrial production

Method used

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  • Method for preparing amoxicillin or ampicillin through full water phase
  • Method for preparing amoxicillin or ampicillin through full water phase
  • Method for preparing amoxicillin or ampicillin through full water phase

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] 1. Take 1000mL of 8%, 15%, 20%, 25% and 30% penicillin GK extract, according to 180U / g substrate, 200U / g substrate, 220U / g substrate, 240U / g substrate and 270U Put into immobilized penicillin G acylase (PGA-6) per g substrate, use 3N ammonia water to control the pH value of 8.0-8.3, temperature 30°C, cleavage time 1-2h, solid-liquid separation after cleavage, volume 1040mL-1200mL.

[0035] 2. Lower the temperature to below 10°C, lower the pH value to 0.5 with 6N hydrochloric acid, and remove the phenylacetic acid crystals by filtration to obtain 1200mL-1400mL 6-APA and phenylacetic acid mixed solution.

[0036] 3. Put 1200mL~1400mL 6-APA and phenylacetic acid mixture on the column (resin F-Z-001250mL), control the flow rate of the upper column to 1000mL / Hr, control the temperature below 10°C during the whole process, after the 6-APA and phenylacetic acid mixture is loaded on the column , wash the chromatography column with 250mL pure water, and then regenerate the chrom...

Embodiment 2

[0041] 1. Put 1000mL of 20% penicillin GK extract into immobilized penicillin G acylase (PGA-6) according to 220U / g substrate, control the pH value to 8.0-8.3 with 3N ammonia water, the temperature is 30°C, and the lysis time is 1-6hr , solid-liquid separation after lysis, volume 1100mL.

[0042] 2. Lower the temperature to below 10°C, lower the pH value to 0.5 with 6N hydrochloric acid, remove the phenylacetic acid crystals by filtration, and obtain 1300 mL of 6-APA and phenylacetic acid mixed solution.

[0043] 3. 1300mL 6-APA and phenylacetic acid mixture, 250mL macroporous adsorption resin (F-Z-001, PDA600, HP20, SP207, LXT-057) on the column, control the flow rate of the upper column to 1000mL / Hr, and control the temperature below 10°C throughout the process , After the mixture of 6-APA and phenylacetic acid is applied to the column, wash the column with 250 mL of pure water, and then regenerate the column with 0.5 N sodium hydroxide. During the process, solutions with a...

Embodiment 3

[0050] 1. 1000mL of 20% penicillin GK&VK extract was put into immobilized penicillin G acylase (IPA-750) (Hunan Fulaige Biotechnology Co., Ltd.), immobilized penicillin G acylase (PGA- 6) and immobilized penicillin V acylase (PVA-4), use 3N ammonia water to control the pH value of 8.0-8.3 (PVA-4 controls the pH value of 7.0), the temperature is 30°C, the lysis time is 1-2hr, and the solid-liquid separation after lysis , volume 1100mL.

[0051] 2. Lower the temperature to below 10°C, lower the pH value to 0.5 with 6N hydrochloric acid, and remove phenylacetic acid or phenoxyacetic acid crystals by filtration to obtain 1300 mL of 6-APA and phenylacetic acid mixed solution or 6-APA and phenoxyacetic acid mixed solution.

[0052] 3. Put 1300mL of 6-APA and phenylacetic acid mixture or 6-APA and phenoxyacetic acid mixture on the column (resin F-Z-001250mL), and collect the solutions with 6-APA concentration greater than 5mg / mL respectively.

[0053] 4. Adjust the pH of the 6-APA c...

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Abstract

The invention discloses a method for preparing amoxicillin or ampicillin in a full-water-phase through mode. The method includes the steps that a high-concentration penicillin GK or penicillin VK extracting solution is used as a raw material, immobilized penicillin G acylase or penicillin V acylase is used as an enzyme catalyst, a high-concentration 6-APA solution or crystal is obtained through full-water-phase operations such as catalytic cracking, separating, acidization, filtering, chromatography and concentration by nanofiltration, and then the amoxicillin or the ampicillin is synthesized by the solution or crystal and HPGME or phenylglycine methyl ester under the catalytic action of the immobilized penicillin synthetase. According to the method, water-phase reacting is conducted in the whole process, no organic solvent is used, and environmental pollution is reduced; besides, the special immobilized penicillin G acylase and the penicillin V acylase are used for cracking the high-concentration penicillin GK or VK extracting solution, and special macroporous absorption resin is used for separating and cracking products, so that the processing steps are greatly simplified, the production cost is lowered, the product yield is increased, and the industrial production requirement is met.

Description

technical field [0001] The invention relates to a method for directly preparing amoxicillin or ampicillin through all aqueous phases, and belongs to the field of biomedicine. Background technique [0002] Amoxicillin and ampicillin are β-lactam antibiotics, and amoxicillin is currently the most widely used oral antibiotic. [0003] At present, there are two processes for the synthesis of amoxicillin: chemical method and enzymatic method. The chemical method is an old process and is still used in a small amount. , crystallization and other procedures to synthesize amoxicillin, the process is complicated, and a large amount of toxic substances are used. [0004] Enzyme method is the current mainstream process. It is mentioned in the Chinese patent (application number CN200410012464.0) that the penicillin lysate is acidified and then added with 25% to 50% of the volume of methyl isobutyl ketone for extraction and separation. 50% to 60% of acetone is added to the volume of the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P37/04
Inventor 许岗曹竟柳杏辉易杰黄斌粟帅譞张娇
Owner HUNAN FLAG BIOTECHNOLOGY CO LTD
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