Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for separation and purification of daptomycin RS-8 impurity

A daptomycin and RS-8 technology, applied in the direction of peptides, etc., can solve the problems of daptomycin resistance, changing the properties of cell plasma membrane, and not specifically involving the separation method of daptomycin impurities

Inactive Publication Date: 2017-06-20
PEKING UNIV FOUNDER GRP CO LTD +2
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The mechanism of action of daptomycin is different from that of other antibiotics. It disrupts the transport of amino acids by the cell membrane, thereby hindering the biosynthesis of peptidoglycan on the bacterial cell wall and changing the properties of the plasma membrane of the cell. In addition, it can also destroy the cell membrane of the bacteria, making Its contents leak out to achieve the purpose of killing bacteria, so it may be difficult for bacteria to develop resistance to daptomycin
[0004] Although daptomycin has been industrialized in the United States, daptomycin products often contain impurities such as dehydrated daptomycin, isomeric daptomycin, and daptomycin lactone hydrolyzate, which seriously affect product quality. , it is very necessary to be able to separate and purify the impurities in daptomycin and conduct research
[0005] Existing methods for extracting daptomycin impurities, such as the attribution of daptomycin impurities described in European Patent No. 1586580A2, do not specifically involve the separation method of daptomycin impurities

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for separation and purification of daptomycin RS-8 impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] After the daptomycin fermentation broth is filtered, the filtrate is chromatographed on FPDA13 resin, and the column is washed with 2BV of 0.03N sodium chloride, 0.06N sodium acetate, and acetic acid to adjust the pH to 6.5-7.0. 0.3N sodium chloride, 0.06N acetic acid Sodium, acetic acid adjusted pH6.5-7.0 solution elution, collect the daptomycin RS-8 impurity with chromatographic purity greater than 40%, through preparative chromatography (mobile phase is acetonitrile:0.01% trifluoroacetic acid=25:75, volume ratio) was separated and purified, and was tracked and detected by high performance liquid phase (the detection conditions were the same as the method disclosed in the European patent "PROCESSFOR THE PURIFICATION OF DAPTOMYCIN" (EP 1 586 580 A2)), and the daptomycin RS- 8 impurity preparation solution.

[0026] The preparation solution was vacuum freeze-dried, and the obtained solid daptomycin RS-8 impurity was detected by high performance liquid chromatography (th...

Embodiment 2

[0028] After filtering the daptomycin fermentation broth, apply FPDA13 resin chromatography on the filtrate, wash the column with 0.03N sodium chloride, 0.06N sodium acetate, and acetic acid to adjust the pH6.5-7.0 solution 2BV, 0.3N sodium chloride, 0.06N sodium acetate , acetic acid to regulate pH6.5-7.0 solution elution, collect the daptomycin RS-8 impurity with chromatographic purity greater than 40%, through preparative chromatography (mobile phase is acetonitrile:0.01% trifluoroacetic acid=30:70, volume ratio ) was separated and purified, and tracked and detected by high performance liquid phase (detection conditions were the same as the method disclosed in the European patent "PROCESS FORTHE PURIFICATION OF DAPTOMYCIN" (EP 1 586 580 A2)), and collected daptomycin RS-8 with a chromatographic purity>90% Impurity preparation solution.

[0029] The preparation solution was vacuum freeze-dried, and the obtained solid daptomycin RS-8 impurity was detected by high performance ...

Embodiment 3

[0031] After filtering the daptomycin fermentation broth, apply FPDA13 resin chromatography on the filtrate, wash the column with 0.03N sodium chloride, 0.06N sodium acetate, and acetic acid to adjust the pH6.5-7.0 solution 2BV, 0.3N sodium chloride, 0.06N sodium acetate , acetic acid to regulate pH6.5-7.0 solution elution, collect the daptomycin RS-8 impurity with chromatographic purity greater than 40%, through preparative chromatography (mobile phase is acetonitrile:0.01% trifluoroacetic acid=33:67, volume ratio ) was separated and purified, and tracked and detected by high performance liquid phase (detection conditions were the same as the method disclosed in the European patent "PROCESS FORTHE PURIFICATION OF DAPTOMYCIN" (EP 1 586 580 A2)), and collected daptomycin RS-8 with a chromatographic purity>90% Impurity preparation solution.

[0032] The preparation solution was vacuum freeze-dried, and the obtained solid daptomycin RS-8 impurity was detected by high performance ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a method for separation and purification of a daptomycin RS-8 impurity; according to the method, an RS-8 impurity crude product liquid is obtained by resin chromatography of a daptomycin filtrate, then by preparative chromatography, the high-purity daptomycin RS-8 impurity with the chromatographic purity of more than 90% is obtained. The method is simple and easy to operate and low in cost.

Description

technical field [0001] The invention relates to the field of medicine preparation, in particular to the separation and purification of daptomycin RS-8 impurities, in particular to a method for preparing high-purity daptomycin RS-8 impurities by using daptomycin resin chromatography and preparative chromatography method. 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 Pharmaceu...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07K7/08C07K1/16
Inventor 赵燕张洪兰谢云
Owner PEKING UNIV FOUNDER GRP CO LTD