Method for producing clavulanic acid kalium with inert carrier adsorption of solid state continuous fermentation

A technology of potassium clavulanate and inert carrier, which is applied in the field of continuous fermentation of potassium clavulanate by adsorption of inert carrier in solid state, and can solve the problems of high energy consumption and low output of potassium clavulanate, achieve low energy consumption and improve production efficiency , to achieve a continuous effect

Active Publication Date: 2008-05-07
SHANXI WEIQIDA PHARMA IND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] The purpose of the present invention is to solve the problems of high energy consumption and low yield in the production of potassium clavulanate, and to provide a method for producing potassium clavulanate by solid-state continuous fermentation with inert carrier adsorption, so as to improve the heat transfer of the fermentation system quality, reduce energy consumption, and increase output

Method used

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  • Method for producing clavulanic acid kalium with inert carrier adsorption of solid state continuous fermentation

Examples

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Effect test

Embodiment 1

[0057] Prepare potassium clavulanate with the method of the present invention, its step is as follows:

[0058] 1) Preparation of Streptomyces clavulicularis seed solution

[0059] Streptomyces clavuligerus (Streptomyces, Clavuligerus, CCRC11518=ATCC27064, whose preservation number is CCMCC 4.3) purchased from the General Microorganism Collection Center of China Microorganism Collection Management Committee was inoculated on the slant medium of Streptomyces clavuligerus, and inoculated and cultivated at 29°C; Cultivate in the Streptomyces clavulicularis seed culture medium to produce mycelium, obtain the Streptomyces clavulinformis seed liquid and dress in figure 1 Streptomyces clavulicularis fermentation seed liquid storage tank 10 in;

[0060] The Streptomyces clavulis slant culture medium is Gao's No. 1 medium, and its contained components and proportions are: soluble starch 20g, KNO 3 1g, MgSO 4 0.5g, K 2 HPO 4 0.5g, NaCl 0.5g, FeSO 4 0.01g, 15-20g agar, 1000ml w...

Embodiment 2

[0076] Prepare potassium clavulanate with the method of the present invention, its step is with embodiment 1, and embodiment 1 difference is:

[0077] The inert carrier used in this embodiment is a polyvinyl chloride foam carrier;

[0078] In step 3) of this embodiment, the Streptomyces clavuliformis fermentation medium storage tank was pumped from the top of the Streptomyces clavuliformis fermentation medium into the fermenter at a flow rate of 0.04 ml / min through a peristaltic pump.

[0079] The flow rate at which the Streptomyces clavulosa seed liquid in the seed liquid storage tank in step 3) of this embodiment is pumped into the fermenter from its top is 0.04 ml / min.

[0080] In step 3) of this embodiment, while the Streptomyces clavulosa culture medium flows from top to bottom and ferments to produce fermentation metabolites, the flow rate of sterile air entering the fermenter from the air inlet at the bottom of the fermenter is 13ml / min.

Embodiment 3

[0082] Prepare potassium clavulanate with the method of the present invention, its step is with embodiment 1, and embodiment 1 difference is:

[0083] The inert carrier used in this embodiment is a polyvinyl chloride foam carrier;

[0084] In step 3) of this embodiment, the Streptomyces clavulicularis fermentation medium storage tank was pumped from the top of the Streptomyces clavuliformis fermentation medium into the fermenter at a flow rate of 0.05 ml / min through a peristaltic pump.

[0085] The Streptomyces clavulosa seed liquid in the seed liquid storage tank in step 3) of this embodiment is pumped into the fermenter at a flow rate of 0.05 ml / min from its top.

[0086] In step 3) of this embodiment, while the Streptomyces clavulosa culture medium flows from top to bottom and ferments to produce fermentation metabolites, the flow rate of sterile air entering the fermenter from the air inlet at the bottom of the fermenter is 15ml / min.

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Abstract

The method for producing potassium clavulanate by solid-state continuous fermentation involving inert carrier adsorption in the present invention: the Streptomyces clavulus seed liquid and the Streptomyces clavulus fermentation medium are dispersed from the top of the fermenter through a distribution plate and flow down to the inert carrier successively, and the seed liquid is filled in In the carrier, the fermentation medium is covered on the carrier to form a liquid film, and the mycelium of the seed liquid grows and reproduces on the liquid film to produce fermentation metabolites. At the same time, sterile air flows from the bottom of the tank through the distribution plate to provide oxygen for fermentation; Adding and overloading of carrier adsorption, fermentation metabolites flow out of the tank; then exchanged with basic anion resin, 5 times the amount of resin containing 1.5% lithium chloride 95% ethanol solution to obtain potassium clavulanate; fermentation process The medium fermentation medium is continuously pumped in and out, and the fermentation metabolites can be continuously obtained with only one inoculation of the strain, realizing continuous fermentation; the fermentation process does not need to be stirred, the heat and mass transfer is good, and the energy consumption is low. Potassium clavulanate has a high yield.

Description

technical field [0001] The invention belongs to the field of antibiotic production, in particular to a method for producing potassium clavulanate by solid-state continuous fermentation with inert carrier adsorption. Background technique [0002] Due to the widespread use of penicillin, some bacteria, especially Staphylococcus aureus, have developed resistance to penicillin; both penicillins and cephalosporins contain a common β-lactam structure and belong to β-lactam antibiotics. When antibiotics with this structure are used, some pathogenic bacteria develop drug resistance through the mechanism of producing β-lactamases. Research and clinical application results show that β-lactamase inhibitors such as potassium clavulanate can greatly improve the sensitivity of the above-mentioned pathogenic bacteria to β-lactam antibiotics. [0003] Potassium clavulanate itself has very weak antibacterial activity, but it is a potent, broad-spectrum β-lactamase inhibitor. Binds both in ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/18C12N1/20C12R1/465
Inventor 陈洪章王麾
Owner SHANXI WEIQIDA PHARMA IND
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