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A method for directly preparing 6-aminopenicillanic acid from penicillin fermentation broth

A fermentation technology of aminopenicillanic acid and penicillin, which is applied in the field of biomedicine, can solve problems such as environmental hazards, high energy consumption, and low membrane filtration flux, so as to reduce energy consumption and cost, avoid environmental pollution, and improve membrane flux. volume effect

Active Publication Date: 2016-09-14
TIANJUSHI ENG TECH GROUP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The 6-APA preparation method starting from RB in the above-mentioned straight-through process still has many disadvantages: a large amount of organic solvents such as butyl acetate and n-butanol are used in the production process, which is harmful to the environment, and the process steps are long. The rectification recovery process consumes a lot of energy such as steam and cooling water
Therefore, the technical disadvantages of this preparation method are that the membrane filtration flux is low, the energy consumption is large, the yield of the product is low and the preparation cost is high

Method used

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  • A method for directly preparing 6-aminopenicillanic acid from penicillin fermentation broth

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Effect test

Embodiment 1

[0033] Embodiment 1 The preparation method of 6-aminopenicillanic acid of the present invention

[0034] Place 1000mL of penicillin fermentation broth with a concentration of 100000u / mL in a stirring reactor whose temperature is controlled at 28-30°C, and stir. When the temperature of the fermentation broth reaches 28-30°C, add penicillin to acylate for cleavage, and continuously add ammonia water with a concentration of 10% dropwise during the cleavage process to maintain the pH value in the reactor at about 7.0. When the addition of ammonia water is stopped When the pH value in the reactor remained constant within the last 20 min, the reaction was terminated.

[0035] The mixed solution after the cleavage reaction was passed through a 10-micron filter and a 1-micron filter to remove solid penicillin hyphae. Then the mixed solution is sequentially passed through an ultrafilter with a molecular weight cutoff of 30000-50000 Daltons and an ultrafilter with a molecular weight cu...

Embodiment 2

[0041] Embodiment 2 The preparation method of 6-aminopenicillanic acid of the present invention

[0042] Place 1000mL of penicillin fermentation broth with a concentration of 100000u / mL in a stirred reactor whose temperature is controlled at 30-32°C, and stir. When the temperature of the fermentation broth reaches 30-32°C, add penicillin to acylate for cleavage, and continuously add ammonia water with a concentration of 5% dropwise during the cleavage process to maintain the pH value in the reactor at about 7.4. When the addition of ammonia water is stopped When the pH value in the reactor remained constant within the last 20 min, the reaction was terminated.

[0043] The mixed solution after the cleavage reaction was passed through a 10-micron filter and a 1-micron filter to remove solid penicillin hyphae. Then the mixed solution is sequentially passed through an ultrafilter with a molecular weight cutoff of 30000-50000 Daltons and an ultrafilter with a molecular weight cuto...

Embodiment 3

[0049] Embodiment 3 The preparation method of 6-aminopenicillanic acid of the present invention

[0050] Place 1000mL of penicillin fermentation broth with a concentration of 100000u / mL in a stirred reactor whose temperature is controlled at 34-36°C and stir. When the temperature of the fermentation broth reaches 34-36°C, add penicillin to acylate for cleavage, and continuously add ammonia water with a concentration of 8% dropwise during the cleavage process to keep the pH value in the reactor at about 8.0. When the pH value in the reactor remained constant within the last 20 min, the reaction was terminated.

[0051] The mixed solution after the cleavage reaction was passed through a 10-micron filter and a 1-micron filter to remove solid penicillin hyphae. Then the mixed solution is sequentially passed through an ultrafilter with a molecular weight cutoff of 30000-50000 Daltons and an ultrafilter with a molecular weight cutoff of 3000-5000 Daltons to remove impurities such a...

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Abstract

The invention belongs to the biological medicine field, and relates to a method using penicillin fermentation liquor for direct preparation of 6-aminopenicillanicacid. Preparation methods of the 6-aminopenicillanicacid in the prior art have the technical problems of large environmental pollution, high energy consumption, low product yield and the like; in order to overcome the technical problems, the invention provides the method using the penicillin fermentation liquor for direct preparation of the 6-aminopenicillanicacid, the method avoids use of butyl acetate, n-butyl alcohol and other organic solvents, improves the product yield, reduces the energy consumption in the process of preparation, is a green energy-saving 6-aminopenicillanicacid production method, and is very suitable for popularization and application in industry.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a method for directly preparing 6-aminopenicillanic acid from a penicillin fermentation liquid. Background technique [0002] 6-aminopenicillanic acid (6-APA) is a white flaky crystal, which is an important intermediate for the synthesis of various semi-synthetic penicillins and has a wide range of uses. Using this as a raw material for chemical structure modification and connecting side chains of different structures can produce new semi-synthetic penicillins that are sensitive to penicillin-resistant bacteria and have a wider antibacterial spectrum, such as ampicillin, amoxicillin, and phenoxymethyl penicillin. Penicillin, and other semi-synthetic penicillins with broader antibacterial spectrum. At present, the annual output of 6-APA in China exceeds 30,000 tons. [0003] At present, there are mainly microbial enzyme-catalyzed cleavage methods and chemical cleavage meth...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D499/42C07D499/18C12P37/06
CPCC07D499/18C07D499/42C12P37/06
Inventor 王京刘秀忠陈钊史静宏李惠敏马忠青张欣巧姚振勇刘东
Owner TIANJUSHI ENG TECH GROUP
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