Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A process for preparing enoxaparin sodium

A technology of enoxaparin sodium and heparin sodium, which is applied in the fields of medicine and chemistry, can solve the problems of low degree of automation, time-consuming, laborious, etc., and achieve the effect of convenient operation, high degree of automation, and increased production capacity

Active Publication Date: 2016-08-17
CHANGZHOU QIANHONG BIOPHARMA
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The object of the present invention is to provide a process for preparing enoxaparin sodium. The method obtains a high-yield and high-purity enoxaparin sodium product by using anion exchange resin chromatography, etc., and the process has a high degree of automation and is easy to operate. It provides a strong guarantee for increasing production capacity and is suitable for large-scale production; it overcomes the time-consuming, laborious, and low degree of automation in the existing technology, which is not suitable for large-scale production and limits the improvement of production capacity.

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
  • A process for preparing enoxaparin sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Process for preparing enoxaparin sodium

[0026] ①Preparation of heparin-benzethonium chloride salt: Dissolve 4kg of heparin sodium in 40kg of purified water, dissolve 4-6kg of benzethonium chloride in 50L of purified water, and slowly add heparin sodium solution to benzethonium chloride with stirring at room temperature In the ammonium solution, continue to stir at room temperature for 1 to 5 hours after the addition is complete, centrifuge the precipitate, wash it repeatedly with purified water, and centrifuge until the filtrate meets 10% silver nitrate solution without turbidity, and vacuum dry the precipitate at 50°C to 60°C After 24 hours, heparin benzethonium chloride salt with a water content of less than 5% was obtained.

[0027] ②Preparation of heparin benzyl ester: dissolve the heparin sodium benzethonium chloride salt obtained in the previous step in a weight ratio of 1:1 (heparin sodium benzethonium chloride salt: dichloromethane) in dichlorometha...

Embodiment 2

[0032] Example 2: Process for preparing enoxaparin sodium

[0033]①Preparation of heparin-benzethonium chloride salt: Dissolve 4kg of heparin sodium in 40kg of purified water, dissolve 5-8kg of benzethonium chloride in 50L of purified water, slowly add heparin sodium solution into benzethonium chloride under stirring at room temperature In the ammonium solution, continue to stir at room temperature for 1 to 5 hours after the addition is complete, centrifuge the precipitate, wash it repeatedly with purified water, and centrifuge until the filtrate meets 10% silver nitrate solution without turbidity, and vacuum dry the precipitate at 50°C to 60°C After 24 hours, heparin benzethonium chloride salt with a water content of less than 5% was obtained.

[0034] ② Preparation of heparin benzyl ester: dissolve the heparin sodium benzethonium chloride salt obtained in the previous step in dichloromethane in a weight ratio of 1: 2 to 3 (heparin sodium benzethonium chloride salt: dichlorom...

Embodiment 3

[0040] The invention creates a process for preparing enoxaparin sodium through anion exchange chromatography technology. Heparin sodium is sequentially subjected to benzethonium chloride salification, benzyl esterification, alkaline degradation, oxidative decolorization, filtration to remove impurities, and the filtrate is subjected to anion exchange chromatography to obtain enoxaparin sodium products whose average molecular weight distribution meets the requirements. The present invention adopts anion exchange resin, distributes and collects eluent, and prepares a stable and controllable quality, high-purity, high-activity enoxaparin product, and the quality is obviously higher than the standard of the current EP Pharmacopoeia (see the table below).

[0041]

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 process for preparing enoxaparin sodium, comprising: S1: preparation of heparin-benzethonium chloride salt S2: preparation of heparin benzyl ester; S3: cracking of heparin benzyl ester S4: preparation of enoxaparin sodium Decolorization; S5: anion exchange chromatography: collect the eluate, detect the molecular weight distribution as the weight average molecular weight of 4000-4600, and the proportion of molecular weight of 2000-8000 is 72‑78%; S6: freeze-drying: alcohol precipitation, sterilization, freeze-drying , to obtain the enoxaparin sodium. The method obtains high-yield and high-purity enoxaparin sodium products by using anion-exchange resin chromatography, etc., and the process has a high degree of automation and convenient operation, which provides a strong guarantee for increasing production capacity and is suitable for large-scale production.

Description

technical field [0001] The invention relates to the preparation of a medicinal chemical in the field of medicine and chemistry, in particular to a process for preparing enoxaparin sodium. Background technique [0002] Heparin has been the drug of choice for the prevention and treatment of thrombosis since the 1980s. Low-molecular-weight heparin (including dalteparin sodium, enoxaparin, and nadroparin) is prepared from unfractionated heparin through specific chemical cleavage and purification. As a result, since Sanofi’s enoxaparin was approved by the US FDA to be marketed in the United States at the end of the last century, low-molecular-weight heparin has gradually replaced the market position of traditional heparin due to its definite curative effect, small side effects and predictable advantages. Enoxaparin can effectively prevent venous thromboembolism and pulmonary embolism, and can be used for orthopedic surgery, neurosurgery preoperative and postoperative thrombosis, ...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/10
Inventor 周翔金晶陶翎费清清王轲
Owner CHANGZHOU QIANHONG BIOPHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com