Extraction method for daptomycin

A technology of daptomycin and its extraction method, which is applied in the field of preparation of daptomycin, can solve problems such as high cost, failure to meet pharmaceutical needs, and damage of daptomycin, and achieve low-cost effects

Active Publication Date: 2013-06-19
NEW FOUNDER HLDG DEV LLC +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] Adjust the pH of the filtrate to 6.0 with dilute acetic acid, then pass through 3 small sections of D101 resin columns connected in series with a diameter of 3.5 cm and a length of 35 cm, disconnect the series connection, wash each small section of column with water unti...

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 6.0 with dilute acetic acid, passed through 3 small sections of D101 resin columns connected in series with a diameter of 3.5 cm and a length of 35 cm, and the series connection was disconnected. Each small section of the colum...

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] Adjust the pH of the filtrate to 6.0 with dilute acetic acid, pass through three small sections of D101 resin columns connected in series with a diameter of 3.5 cm and a length of 35 cm, disconnect the series connection, wash each small section of column with water until the effluent of each se...

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Abstract

The invention discloses an extraction method for daptomycin. The method comprises the following steps of: forming micelles from daptomycin in fermentation solution and filtering the micelles via a ceramic membrane system at first; then performing separation and purification by virtue of a multi-section macroporous adsorption resin separation system and a weak-base anion-exchange resin separation system; and finally concentrating and freeze-drying to obtain a daptomycin solid having a chromatographic purity of greater than 96%. The method disclosed by the invention is simple and practicable, low in cost, and 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 from fermentation liquid by using ceramic membrane filtration and resin chromatography technology. 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 a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K1/36C07K1/34C07K1/18C07K1/16
Inventor 赵燕张洪兰
Owner NEW FOUNDER HLDG DEV LLC
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