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Method for separating and purifying daptomycin

A technology for the separation and purification of daptomycin, applied in peptide preparation methods, chemical instruments and methods, organic chemistry, etc., can solve problems such as high cost, inability to achieve separation and purification, and damage to daptomycin, and achieve low cost Effect

Inactive Publication Date: 2013-01-16
PEKING UNIV FOUNDER GRP CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Existing daptomycin extraction methods, such as the daptomycin extraction method described in Chinese patent application 200910058577.7, only use macroporous resin to separate and purify daptomycin, and the chromatographic purity of the obtained daptomycin is only 80%- 90%, not only cannot meet the pharmaceutical demand, but also cannot realize industrial production because of its high cost
Although Chinese patent application 200910085837.X uses ion exchange resin method to obtain high-purity daptomycin, the purpose of separating and purifying daptomycin cannot be achieved due to the problem that daptomycin is severely damaged

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] After adjusting the daptomycin fermentation broth to pH 3.0 with phosphoric acid, filter through a ceramic membrane with a pore size of 0.05 μm to remove water-soluble proteins, pigments and other macromolecular substances in the daptomycin fermentation broth, and then use the raw material solution 1-2 Double the volume of phosphoric acid aqueous solution of pH 3.0 to wash the ceramic membrane circularly (the filtrate is discarded), and then use 4-5 times the volume of the raw material solution to circularly wash the ceramic membrane with pH 9.0 sodium hydroxide solution to obtain the ceramic membrane filtrate, and the obtained filtrate is clear and transparent , and the color is reddish yellow.

[0023] The filtrate was adjusted to pH 5.5 with dilute acetic acid, passed through D301 resin, washed with water, and then eluted with 300 mM NaCl solution at pH 5.5-6.0.

[0024] The obtained eluate was adjusted to pH 4.0-4.5 with dilute acetic acid and passed through HZ20 re...

Embodiment 2

[0028] After adjusting the daptomycin fermentation broth to pH 3.5 with phosphoric acid, filter through a ceramic membrane with a pore size of 0.05 μm to remove water-soluble proteins, pigments and other macromolecular substances in the daptomycin fermentation broth, and then use the raw material solution 1-2 The phosphoric acid aqueous solution of twice the volume of pH3.0 washes the ceramic membrane circularly (the filtrate is discarded), and then the sodium hydroxide solution of the pH10 of 4-5 times the volume of the raw material liquid is used for circular washing of the ceramic membrane to obtain the ceramic membrane filtrate, and the gained filtrate is clear and transparent, and The color is reddish yellow.

[0029] The filtrate was adjusted to pH 5.5 with dilute acetic acid, passed through D301 resin, washed with water, and then eluted with 300 mM NaCl solution at pH 5.5-6.0.

[0030] The resulting eluate was adjusted to pH 4.0-4.5 with dilute acetic acid, and 0.1 time...

Embodiment 3

[0034] After adjusting the daptomycin fermentation broth to pH 3.0 with phosphoric acid, filter through a ceramic membrane with a pore size of 0.05 μm to remove water-soluble proteins, pigments and other macromolecular substances in the daptomycin fermentation broth, and then use 0.5-1 Double the volume of pH 3.0 phosphoric acid aqueous solution to wash the ceramic membrane circularly (the filtrate is discarded), and then use 2-3 times the volume of the raw material solution to circularly wash the ceramic membrane with a pH 10.0 sodium hydroxide solution to obtain the ceramic membrane filtrate, and the obtained filtrate is clear and transparent , and the color is reddish yellow.

[0035] The filtrate was adjusted to pH 6.0-7.0 with dilute acetic acid, passed through D301 resin, washed with water, and then eluted with 300 mM NaCl solution at pH 6.0-7.0.

[0036] The resulting eluate was adjusted to pH 4.0-4.5 with dilute acetic acid, and 0.1 times the volume of ethanol was adde...

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Abstract

The invention discloses a method for separating and purifying daptomycin. The method comprises the steps of allowing daptomycin to form micelles, filtering by a ceramic membrane system, performing separation and purification and discoloring treatment by using a weak-base anion exchange resin separating system and a macroporous resin separating system, crystallizing, and thus a daptomycin solid with a chromatographic purity higher than 98% is obtained. The method is simple and practicable, is low in cost, and is suitable for industrialized production.

Description

technical field [0001] The invention relates to a preparation method of daptomycin, in particular to a method for preparing high-purity daptomycin by using ceramic membrane filtration, resin chromatography and crystallization techniques. Background technique [0002] With the development of antibiotics and the abuse of antibiotics, the resistance of pathogenic bacteria to antibiotics is the most severe challenge facing society today. In addition to controlling the abuse of antibiotics, finding an effective antibiotic against drug-resistant bacteria has become the best way to solve this problem. Vancomycin was once considered the last line of defense against Gram-positive bacteria, but now it is More and more bacteria resistant to this drug have been found clinically in the world. [0003] Daptomycin is a lipopeptide antibiotic originally researched by Lilly and developed by Cubist Pharmaceuticals. In response to the urgent needs of patients for new drug-resistant antibioti...

Claims

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Application Information

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IPC IPC(8): C07K7/08C07K1/36C07K1/34C07K1/18C07K1/16
Inventor 赵燕赵德肖祖梅
Owner PEKING UNIV FOUNDER GRP CO LTD
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