A kind of preparation technology of nadroparin calcium

A technology of nadroparin calcium and preparation technology, applied in the preparation technology of fine nadroparin calcium and the preparation of medicinal chemicals, can solve the problems of low yield, high cost, low degree of automation of separation methods, etc. Convenience, increased productivity, and high degree of automation

Active Publication Date: 2016-07-06
CHANGZHOU QIANHONG BIOPHARMA
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a preparation process of nadroparin calcium, which controls the molecular weight of low molecular weight heparin calcium through anion exchange chromatography, so that the molecular weight can be accurately controlled within 1%, and the yield can be increased to 50% at the same time Above, with high degree of automation and convenient operation, it provides a strong guarantee for increasing production capacity; it overcomes the shortcomings of low yield, high cost and low degree of automation in the separation method in the prior art

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 kind of preparation technology of nadroparin calcium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Embodiment 1: the preparation of nadroparin calcium

[0023] Degradation of heparin sodium: Feed 30kg of heparin sodium, dissolve in purified water 21 to 30 times the weight of heparin sodium, adjust the pH to 5.5 to 6, add 4.5% to 5% of sodium nitrite, and keep warm at 10°C to 30°C Stir and react the degradation solution for 3-6 hours.

[0024] Reduction of the degradation solution: adjust the pH of the degradation solution to neutral, add 1.5% to 2% of the sodium borohydride of the heparin sodium, and stir and react at 10°C to 30°C for 12 to 24 hours to obtain a degradation reduction solution.

[0025] Ultraviolet irradiation: Insert a 254nm ultraviolet lamp into the reducing solution at room temperature and irradiate for 45 to 90 minutes to eliminate residual nitroso compounds in the solution and reduce the content of N-NO groups.

[0026] Calcium transfer and concentration: the reducing solution is ultrafiltered on a 1000Da ultrafiltration membrane with a 5% calciu...

Embodiment 2

[0029] Embodiment 2: the preparation of nadroparin calcium

[0030] Degradation of heparin sodium: Feed 30kg of heparin sodium, dissolve in purified water 15 to 20 times the weight of heparin sodium, adjust the pH to 4.5, add 2% to 2.3% of sodium nitrite, keep warm at 15°C to 30°C and stir for reaction 3 to 6 hours of degradation solution.

[0031] Reduction of the degradation solution: adjust the pH of the degradation solution to neutral, add 0.6% to 1% of the sodium borohydride of the heparin sodium, and stir and react at 15°C to 20°C for 12 to 24 hours to obtain a degradation reduction solution.

[0032] Ultraviolet irradiation: Insert a 254nm ultraviolet lamp into the reducing solution at room temperature and irradiate for 45 to 90 minutes to eliminate residual nitroso compounds in the solution and reduce the content of N-NO groups.

[0033] Calcium transfer and concentration: the reducing solution is ultrafiltered on a 1000Da ultrafiltration membrane with a 5% calcium ch...

Embodiment 3

[0036] Embodiment 3: the preparation of nadroparin calcium

[0037] Degradation of heparin sodium: Feed 30kg of heparin sodium, dissolve in purified water 10 to 14 times the weight of heparin sodium, adjust the pH to 5, add 3% to 4% of sodium nitrite, keep warm at 20°C to 30°C and stir for reaction 3 to 6 hours of degradation solution.

[0038] Reduction of the degradation solution: adjust the pH of the degradation solution to neutral, add 0.5% to 0.8% of the sodium borohydride of the heparin sodium, and stir and react at 10°C to 30°C for 12 to 24 hours to obtain a degradation reduction solution.

[0039] Ultraviolet irradiation: Insert a 254nm ultraviolet lamp into the reducing solution at room temperature and irradiate for 45 to 90 minutes to eliminate residual nitroso compounds in the solution and reduce the content of N-NO groups.

[0040] Calcium transfer and concentration: the reducing solution is ultrafiltered on a 1000Da ultrafiltration membrane with 17 to 20 times th...

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 preparation process of nadroparin calcium, comprising the following steps: S1 degradation of heparin sodium; S2 reduction of degradation solution; S3 ultraviolet irradiation: using an ultraviolet lamp to irradiate the reduction solution to eliminate residual nitroso groups in the reduction solution compound, reducing the N-NO group content; S4 calcium transfer and concentration: use 5% calcium chloride solution to ultrafilter on the ultrafiltration membrane, and concentrate the reducing solution to a concentration of 1:10 in the solid-liquid ratio; S5 anion exchange layer Analysis: use anion exchange resin for chromatography, and collect the eluate; S6 freeze-drying to obtain the nadroparin calcium. The process uses anion exchange chromatography to control the molecular weight of low-molecular-weight heparin calcium, so that the molecular weight can be accurately controlled within 1%, and the yield can be increased to more than 50%, and the degree of automation is high, and the operation is convenient, which provides a powerful way to increase production capacity. Assure.

Description

technical field [0001] The present invention relates to the preparation of a kind of pharmaceutical chemicals in the fields of medicine and chemistry, in particular to a preparation process of high-quality and high-purity high-quality nadroparin calcium. Background technique [0002] Unfractionated heparin is a mixture of several glucosamines. Calcium heparin can delay or prevent blood clotting both in vivo and in vitro. Its anticoagulant mechanism is complex and has effects on all aspects of blood coagulation, including inhibiting the conversion of prothrombin into thrombin, inhibiting the activity of thrombin, hindering the conversion of fibrinogen into fibrin, and preventing platelet aggregation. Calcium heparin can also lower blood lipids, lower LDL and VLDL, raise HDL, change blood viscosity, protect vascular endothelial cells, prevent atherosclerosis, promote blood flow, and improve coronary circulation. [0003] The anti-FIIa effect of heparin calcium is stronger th...

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): C08B37/10A61P7/02A61P35/00A61P29/00A61P37/08
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 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