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Preparation method of high-purity Daptomycin

A technology of daptomycin and daptomycin bacteria, which is applied in the preparation methods of peptides, chemical instruments and methods, organic chemistry, etc., can solve problems such as the inability to meet the needs of pharmaceuticals

Active Publication Date: 2010-12-01
ANHUI BBCA FERMENTATION TECH ENG RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Separation by macroporous adsorption resin, the content of the obtained purified solution is only about 80%, which cannot meet the needs of pharmaceuticals

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] First, the daptomycin fermentation broth is filtered through an organic flat ultrafiltration membrane with a molecular weight cut-off of 100,000. The average membrane flux can reach 60LMH. The amount of water added is 1.5 times that of the raw material solution, and the final concentration is 2 times. The average yield of ultrafiltration membrane filtration can reach 99%. Filtration through a large-volume ultrafiltration membrane system removes mycelium and most macromolecular substances (such as soluble protein, culture medium and some pigments). The filtrate has high clarity and good quality, which can meet the production process requirements.

[0027] The filtrate is further concentrated through the nanofiltration membrane, and desalted and decolorized. The nanofiltration membrane is a roll-type nanofiltration membrane with a molecular weight cut-off of 500. The average membrane flux is 25LMH. The amount of water added is controlled at about 0.5 times the original ult...

Embodiment 2

[0032] First, the daptomycin fermentation broth is filtered through an organic flat ultrafiltration membrane with a molecular weight cut-off of 50,000. The average membrane flux can reach 60LMH. The amount of water added is 2.5 times that of the raw material solution, and the final concentration is 3 times. The average yield of ultrafiltration membrane filtration can reach 99%. Filtration through a large-volume ultrafiltration membrane system removes mycelium and most macromolecular substances (such as soluble protein, culture medium and some pigments). The filtrate has high clarity and good quality, which can meet the production process requirements.

[0033] The filtrate is further concentrated through the nanofiltration membrane, and desalted and decolorized. The nanofiltration membrane is a roll-type nanofiltration membrane with a molecular weight cut-off of 800. The average membrane flux is 25LMH. The amount of water added is controlled at about 1.5 times that of the origi...

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PUM

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Abstract

The invention provides a preparation method of high-purity Daptomycin, which comprises the steps of: first removing mycelium, soluble protein, culture medium, partial pigments and the like from fermented liquid by adopting primary membrane filtration; then concentrating by a secondary membrane filtration system to remove some micromolecular impurities like monosaccharide and a large number of inorganic salts so as to result in clarified Daptomycin concentrated solution; and then causing the clarified Daptomycin concentrated solution to be subject to chromatography of cation exchange resin and neutralization of anion exchange resin as well as nanofiltration membrane concentration and normal reduced pressure concentration in order to obtain high-purity Daptomycin by means of crystallization. Based on the comprehensive usage of membrane separation technology and resin chromatography technology, the invention provides a production-feasible and operationally-easy method for preparing high-purity Daptomycin.

Description

technical field [0001] The invention relates to a method for preparing daptomycin, in particular to a method for preparing high-purity daptomycin by membrane separation and resin chromatography. Background technique [0002] The resistance of pathogenic bacteria to antibiotics is one of the severe challenges facing the world today, and finding antibiotics that can effectively inhibit drug-resistant bacteria is the fundamental way to solve this problem. Vancomycin was once considered the last line of defense against Gram-positive bacteria, but more and more bacteria resistant to this drug have been found clinically all over the world. [0003] Daptomycin (Daptomycin) is recognized as the best backup antibiotic after vancomycin. It is a new type of lipopeptide antibiotic discovered by Eli Lilly and Company in the 1980s. Inhibitory effect, in addition to anti-MRSA, daptomycin also inhibits the vast majority of Gram-positive bacteria. According to reports, daptomycin has an in...

Claims

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Application Information

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IPC IPC(8): C07K7/08C07K1/36C07K1/34C07K1/18
Inventor 余永柱尚海涛郑珩张彦潘声龙
Owner ANHUI BBCA FERMENTATION TECH ENG RES
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