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

Method for producing and purifying enoxaparin sodium

A technology of enoxaparin sodium and purified water, which is applied in the production and purification of enoxaparin sodium, can solve problems such as difficulty in meeting environmental impact assessment requirements, large environmental pollution, and unsuitability for industrial application, and achieve good product clarity, The effect of easy purification operation

Active Publication Date: 2015-03-25
SUZHOU ERYE PHARMA CO LTD
View PDF3 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, the enoxaparin sodium intermediate obtained after acid neutralization and alcohol precipitation often has poor clarity. If it is not refined and purified, it cannot meet the requirements of clarity in the Pharmacopoeia
[0006] The existing purification methods are mainly divided into the following types: (1) Decolorize enoxaparin sodium with activated carbon, filter through macroporous resin, and freeze-dry the filtrate to obtain purified enoxaparin sodium. This method has a better decolorization effect, but the disadvantages are There will be a large amount of products adsorbed in activated carbon and resin, and the yield can only reach about 60%; (2) Adjust the pH of enoxaparin sodium with sodium hydroxide, decolorize with hydrogen peroxide, wash with sodium chloride and ethanol, and freeze-dry , to obtain purified enoxaparin sodium. This method requires the use of highly oxidizing hydrogen peroxide, which will easily lead to the production of other by-products while removing the pigment, and it will pollute the environment greatly, and it is difficult to meet the requirements of the environmental impact assessment; (3) will Enoxaparin sodium passes through hydrophobic chromatography column and anion exchange resin in sequence, and after desalination by nanofiltration, precipitation and drying obtain purified enoxaparin sodium. This method requires multiple chromatography columns, and the product loss is very large; (4) Enoxaparin sodium is passed through filtration, microfiltration and ultrafiltration devices in sequence, and purified enoxaparin sodium is obtained after freeze-drying. The product loss of this method is small, but the operating pressure of this graded ultrafiltration is relatively high, which is not suitable for industrial use. Application; (5) Treat enoxaparin sodium with sodium chloride solution and methanol repeatedly to finally obtain enoxaparin sodium with up to standard clarity. This method is simple to operate and easy to realize in industry, but its purification effect is poor, and It is difficult to accurately determine the number of repeated treatments each time, which is not conducive to the establishment of production standards

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1: Preparation of Crude Enoxaparin Sodium

[0021] Step (1): Preparation of heparin benzethonium chloride salt

[0022] Put 1 kg of heparin sodium and 20 L of purified water into the reaction tank, stir for about 20 minutes, and transfer to the elimination tank after the dissolution is complete. Put 2.5kg of benzethonium chloride and 20L of purified water into the reaction tank, and stir for about 20 minutes. After the dissolution is complete, the benzethonium chloride solution is pumped into the elimination tank, and stirred for 30 minutes. Add 60 L of supplemented purified water into the elimination tank, continue stirring for 10 minutes, and let stand for 30 minutes. The reaction mixture was filtered, and the filter cake was beaten three times with purified water (50kg, 50kg, 60kg). Collect the filter cake and dry it under vacuum for 10 hours in hot water at 60°C±2°C and a vacuum degree greater than 0.08MPa to obtain 2.1kg of heparin benzethonium chloride s...

Embodiment 2

[0027] Example 2 Purification of Enoxaparin Sodium

[0028] 1.1 kg of the crude enoxaparin sodium prepared in Example 1 was put into 5 L of 10% sodium chloride solution, stirred and dissolved to obtain a crude enoxaparin sodium solution, which was filtered to obtain a filtrate. Put the filtrate in a centrifuge at 2000 r / min for 30 minutes to obtain supernatant and precipitate. 10L of ethanol was added to the supernatant, stirred for 1 h and then allowed to stand for 3 h to obtain a precipitate. The precipitate was dissolved into a 10wt~15wt% solution with purified water, filtered through a 0.1μm filter membrane, and then spray-dried to obtain 1.02kg of enoxaparin sodium finished product, with a purification yield of 92.7%.

Embodiment 3

[0029] Example 3 Purification of Enoxaparin Sodium

[0030] 1.1 kg of the crude enoxaparin sodium prepared in Example 1 was put into 10 L of 5% sodium chloride solution, stirred and dissolved to obtain a crude enoxaparin sodium solution, which was filtered to obtain a filtrate. Put the filtrate in a centrifuge at 2000 r / min for 30 minutes to obtain supernatant and precipitate. 10L of methanol was added to the supernatant, stirred for 1.5h and then allowed to stand for 5h to obtain a precipitate. The precipitate was dissolved into a 10wt~15wt% solution with purified water, filtered through a 0.1 μm filter membrane, and then spray-dried to obtain 1.01 kg of enoxaparin sodium finished product, with a purification yield of 91.8%.

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

PropertyMeasurementUnit
absorbanceaaaaaaaaaa
Login to View More

Abstract

The invention relates to a method for producing and purifying enoxaparin sodium. The finished enoxaparin sodium which satisfies the pharmacopeia standards can be obtained through carrying out centrifugal separation and alcohol precipitation purification. The method is high in yield, simple and convenient to operate and good in product clarity, and is capable of satisfying the requirements of the pharmaceutical industry.

Description

[0001] technical field [0002] The invention relates to a production and purification method of enoxaparin sodium, which belongs to the field of pharmacy. Background technique [0003] Heparin has been the drug of choice for the prevention and treatment of thrombosis since the 1980s. Low-molecular-weight heparin is made from unfractionated heparin through specific chemical cutting and purification. Due to its definite curative effect, small and predictable side effects, it has gradually replaced the market position of traditional heparin. [0004] Enoxaparin Sodium (Enoxaparin Sodium) belongs to low molecular weight heparin, and its main feature is that there is a 4-enepyranuronic acid structure in the molecule. This product has strong antithrombotic effect and low risk of bleeding, and is currently one of the main therapeutic drugs for anticoagulation and antithrombosis. [0005] Enoxaparin sodium is obtained by alkaline depolymerization of benzyl ester derivatives of po...

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 Applications(China)
IPC IPC(8): C08B37/10
Inventor 陈学文姚蝉艳张健陈洋洋
Owner SUZHOU ERYE PHARMA CO LTD
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