Production method for purifying enoxaparin sodium

A technology of enoxaparin sodium and its production method, which is applied in the direction of chemical instruments and methods, other chemical processes, etc., can solve the problems that cannot be achieved, residual pigments cannot be further separated, and affect the quality of enoxaparin finished products, so as to achieve easy industrial production Effect

Inactive Publication Date: 2006-10-25
HANGZHOU JIUYUAN GENE ENG
View PDF14 Cites 19 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since enoxaparin is a hydrophilic polysaccharide, general purification processes such as activated carbon adsorption can remove part of the pigment, but the residual pigment cannot be further separated and c

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
  • Production method for purifying enoxaparin sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1, the preparation of enoxaparin sodium

[0031] 1.1 Salification of heparin with long-chain quaternary ammonium salts in aqueous media

[0032] Weigh 100g of heparin raw material and 20g of sodium chloride and dissolve in 1L of water, slowly add 800ml of 95% ethanol at room temperature, after precipitation overnight, remove the supernatant, add 1L of water to dissolve the precipitation. Weigh 250 g of benzylethylammonium and dissolve it in 1 L of water, slowly add it into the heparin solution, and stir. The precipitate was filtered, washed with water, filtered and dried to obtain about 327 g of heparin sodium quaternary ammonium salt.

[0033] 1.2 Benzyl esterified heparin

[0034] The above heparin sodium quaternary ammonium salt was dissolved in 1.2L of dichloromethane, 350ml of benzyl chloride was slowly added, and stirred at 35°C for 25 hours. In addition, 200g of sodium acetate was weighed and dissolved in 2L of methanol, slowly added to the above di...

Embodiment 2

[0037] Embodiment 2, decolorization method one

[0038] Weigh 23 grams of crude enoxaparin, add water to dissolve, and the colorimetry is equivalent to the yellow No. 3 color specified in European Pharmacopoeia 4. Add activated carbon, stir at 100rpm for 40 minutes, filter with filter paper to remove activated carbon, and then filter with microporous membrane to remove residual activated carbon. Put the enoxaparin sodium solution on a H103 non-polar macroporous polystyrene adsorption resin column (manufactured by Nankai University Chemical Factory), with a column bed volume of 150 ml, and elute with water to collect the target peak. The collected solution was eluted twice on the column to collect the target peak. The colorimetry was better than the yellow No. 5 color specified in European Pharmacopoeia 4, and close to the yellow No. 6 color. The collected solution was precipitated with ethanol, filtered, freeze-dried, and weighed to obtain 18.8 g. After testing, the indicato...

Embodiment 3

[0044] Embodiment 3: decolorization method two

[0045] Weigh 30 grams of enoxaparin crude product, add water to dissolve, and the colorimetry is close to the yellow No. 3 color specified in European Pharmacopoeia 4. Put the enoxaparin solution on an XAD-7HP polar macroporous polyalkylene ester adsorption resin column (manufactured by Rohm Haas), with a column bed volume of 120 ml, and elute with water to collect the target peak. The column was eluted for 2 more times, and the target peak was collected, and the colorimetry was yellow No. 4 color defined in European Pharmacopoeia 4. Add activated carbon, stir at 100rpm for 40 minutes, filter with filter paper to remove activated carbon, and then filter with microporous membrane to remove residual activated carbon. The colorimetry is better than the yellow No. 5 color specified in European Pharmacopoeia 4. The collected solution was precipitated by ethanol, filtered, freeze-dried, and weighed to obtain 26.4 grams. After testin...

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 relates to a purifying manufacture method for Yino sodium heparin that adopts long chain quaternary ammonium salt salinization heparin, after taking benzyl chloride esterification, gaining the raw Yino heparin raw product. After taking decoloration by active carbon and macropore adsorptive resin, the sodium heparin product could be gained. The invention is easy to realize industrializing producing.

Description

technical field [0001] The invention relates to a method for purifying and producing low molecular weight heparin sodium, in particular to a method for purifying and producing enoxaparin sodium. Background of the invention [0002] The English name of enoxaparin sodium is enoxaparin sodium. According to the definition of European Pharmacopoeia 4, its chemical structure is as follows: [0003] [0004] Among them, n is an integer of 1-21, R is H or SO 3 Na, R' is H or SO 3 Na or CO-CH 3 , when R2 is H, R3 is CO 2 Na or when R2 is CO 2 When Na, R3 is H. [0005] According to the provisions of European Pharmacopoeia 4, enoxaparin sodium belongs to the low molecular weight heparin family. It is obtained from heparin sodium salt extracted from pig intestinal mucosa through benzyl esterification and alkaline depolymerization. The average molecular weight is 4500 The main feature is a 4-enolpyranuronic acid structure at the non-reducing end of the molecule. [0006] The m...

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): C08B37/10B01J20/26
Inventor 金飞李辉阮德桂施吉顺陈巍徐飞虎
Owner HANGZHOU JIUYUAN GENE ENG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap