A method for purifying clavulanic acid from fermentation broth

Abstract

The invention discloses a method for purifying clavulanic acid from fermentation liquor. The method comprises the steps of performing ultrafiltration treatment on the fermentation liquor and removing solids and partial coloring matters in the fermentation liquor to obtain penetrating fluid A; performing first stage nanofiltration treatment on the penetrating fluid A and removing proteins and surplus coloring matters in the penetrating fluid A to obtain penetrating fluid B; performing second stage nanofiltration treatment on the penetrating fluid B and removing partial water in the penetrating fluid B to obtain intercepted concentrated liquor C; and performing extraction separation on the concentrated liquor C to prepare purification liquid of the clavulanic acid. Solid bodies, the proteins, sugars and the coloring matters in the fermentation liquor can be effectively removed through the ultrafiltration treatment and the first stage nanofiltration treatment, so that the concentrated liquor C can be easily layered in a subsequent extraction separation process, excessive emulsion can be avoided, high speed centrifugation treatment is not needed, and investment cost of equipment can be greatly reduced.

Description

technical field [0001] The invention relates to a method for purifying clavulanic acid from fermentation broth. Background technique [0002] Clavulanic acid is also known as clavulanic acid, chemical name (2R,5R,Z)~30(2~hydroxyethylene)~7~oxo~4~oxa~1~azabicyclo[3.2.0]heptane Alkane ~ 2 ~ carboxylic acid, the molecular formula is: [0003] [0004] It is an irreversible competitive β-lactamase inhibitor produced by Streptomyces, which is effective against Staphylococcus aureus, Escherichia coli, Klebsiella, Shigella, Pseudomonas and influenza The β-lactamase of various pathogenic bacteria such as blood bacteria has a strong inhibitory effect. Because clavulanic acid can increase the antibacterial activity spectrum of antibiotics, its combined use with penicillins and cephalosporins can increase the efficacy by several times or even ten times, and at the same time restore the sensitivity to drug-resistant strains, so it has a high Medicinal value. [0005] At present, ...

AI Technical Summary

Problems solved by technology

Although this scheme can prepare or extract clavulanic acid or its pharmaceutically acceptable salt or ester, in the whole scheme, microfiltration and ultrafiltration (10-30 kilodaltons) are used to purify the fermentation broth, Although the suspended solids in the fermented liquid can be removed, the pigments, proteins and sugar components with smaller molecular weights contained in the fermented liquid cannot be removed, so the purity of the obtained clavulanic acid solution is low, containing a small amount of pigments, sugars Part and protein, there will be serious emulsification in the subsequent extraction process, which will affect the subsequent operations such as the separation and salt formation of clavulanate. At the same time, it is necessary to use activated carbon to further depigmentation treatment in the subsequent operations; Or it uses reverse osmosis to concentrate the fermentation broth, which has high energy consumption and slow concentration rate, and the whole production process takes a long time

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