Method for preparing high-quality low molecular parnaparin sodium

A panaparin and low-molecular-weight technology, which is applied in the field of preparation of high-quality low-molecular-weight panaparin, can solve the problems of insufficient purity of low-molecular-weight heparin samples, affect the stability of preparations, and non-concentrated molecular weight distribution, and achieve half-life in vivo Long, advanced technology and feasible, simple operation effect

Active Publication Date: 2013-12-04
山东辰龙药业有限公司
View PDF4 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In its preparation process, high-quality heparin sodium is used as a raw material, and it is difficult to control the quality of the final product from the source of the raw material; 2+ In the presence of , heparin reacts with peroxides under alkaline conditions to degrade
This degradation reaction is relatively random, and the glycosidic bonds between uronic acid and glucosamine may be broken, resulting in the prepared low-molecular-weight heparin samples having insufficient purity, non-concentrated molecular weight distribution, and excessive residual impurities. Many disadvantages, which in turn will affect the stability of the drug preparations, and are prone to certain risks during use
Moreover, after degradation, the metallic Cu 2+ During the removal process, 001x7 resin is used, which will cause the product to be partially adsorbed, reducing the yield of the product

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 preparing high-quality low molecular parnaparin sodium
  • Method for preparing high-quality low molecular parnaparin sodium
  • Method for preparing high-quality low molecular parnaparin sodium

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0041] a) Enzymolysis: Take 800 g of crude heparin sodium, add 8 kg of water to dissolve it, adjust the pH of the feed solution to 8.4 with 20% (w / v) sodium hydroxide solution, and control the temperature of the feed solution to 37°C. Add 42g of papain and 36g of ribonuclease II to the feed solution, stir for 8 hours, centrifuge to remove the precipitate, filter the supernatant with a plate and frame filter, and collect 7.6L of filtrate;

[0042]b) Oxidation: control the temperature of the filtrate in step a) to 32°C, adjust the pH of the feed liquid to 9.7, add 35ml of hydrogen peroxide, stir and react for 5 hours under temperature control and pH control, and obtain a purified solution; after the oxidation is completed, use 4mol / L The HCl adjustment feed liquid pH is 6.9, after adding 72g sodium chloride wherein to dissolve, filter with the millipore filter of 0.65um, add after filtering and add 8L95% ethanol in the filtrate, leave standstill 10 hours after stirring. After st...

preparation Embodiment 2

[0051] a) Enzymolysis: Take 1000 g of crude heparin sodium, add 12 kg of water to dissolve it, adjust the pH of the feed solution to 8.2 with 20% (w / v) sodium hydroxide solution, and control the temperature of the feed solution to 36°C. Add 60 g of papain and 48 g of ribonuclease II to the feed solution, stir for 9 hours, centrifuge to remove the precipitate, filter the supernatant with a plate and frame filter, and collect 972 L of filtrate;

[0052] b) Oxidation: control the temperature of the filtrate in step a) to 36°C, adjust the pH of the feed liquid to 10.2, add 46ml of hydrogen peroxide, and stir and react for 5 hours under temperature and pH control to obtain a purified solution; after the oxidation is completed, use 4mol / L The HCl adjustment feed liquid pH is 7.1, after adding 90g sodium chloride wherein to dissolve, filter with the millipore filter of 0.65um, add after filtering and add 11L95% ethanol in the filtrate, leave standstill 10 hours after stirring. After ...

preparation Embodiment 3

[0061] a) Enzymolysis: Take 800 g of crude heparin sodium, add 8 kg of water to dissolve it, adjust the pH of the feed solution to 8.1 with 20% (w / v) sodium hydroxide solution, and control the temperature of the feed solution to 36°C. Add 45g of papain and 36g of ribonuclease II to the feed solution, stir for 8 hours, centrifuge to remove the precipitate, filter the supernatant with a plate and frame filter, and collect 7.8L of the filtrate;

[0062] b) Oxidation: Control the temperature of the filtrate in step a) to 34°C, adjust the pH of the feed liquid to be between 9.8, add 26ml of hydrogen peroxide, and stir and react for 4.5 hours under temperature and pH control to obtain a purified solution; after oxidation, use 4mol The HCl of / L regulates feed liquid pH to be 6.8, after adding 63g sodium chloride wherein to dissolve, filter with the millipore filter of 0.65um, add again after filtering, add 8L95% ethanol in the filtrate, leave standstill 10 hours after stirring . Af...

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
molecular weightaaaaaaaaaa
Login to view more

Abstract

The invention discloses a method for preparing high-quality low molecular parnaparin sodium, belonging to the field of biological medicine. The method comprises the following steps: using a coarse-product heparin sodium as a raw material, carrying out enzymolysis to the coarse-product heparin sodium through papain and ribonuclease II, oxidation-decoloring and purifying to obtain competitive-product heparin sodium; after dissolving the competitive-product heparin sodium, conducing degradation reaction under the action of a copper acetate catalyst and hydrogen peroxide; after completing the degradation reaction, using a heavy metal absorbent to remove Cu2+ or removing Cu2+ in an ultra-filtration mode, and then separating though a low molecular membrane to obtain a parnaparin sodium coarse-product with specific molecular weight; after decoloring and, alcohol-precipitating the parnaparin sodium coarse-product, and vacuum-freezing and drying to obtain a low molecular parnaparin sodium finished-product with the anti-Xa factor activity being 80-i10 IU/mg, the pH value being 5.5-8.0 and the average molecular weight being 4000-6000D.The preparation process is simple, the stability and antithrombotic activity of the product are good.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a method for preparing high-quality low-molecular-weight parnaparin. Background technique [0002] Heparin is a highly sulfated glycosaminoglycan with anticoagulant and antithrombotic effects in vivo and in vitro. However, unfractionated heparin has defects such as low bioavailability, large side effects, and short half-life. Panaparin is a substitute product of low-molecular-weight heparin, which has the advantages of prolonged half-life in vivo, high bioavailability, and low bleeding risk. It is the current mainstream antithrombotic anticoagulant drug. [0003] Low-molecular-weight panaparin is obtained by dissolving heparin to a certain concentration, adding a certain amount of sodium chloride and sodium acetate, adding a copper acetate catalyst under specific temperature and pH conditions, and degrading it by hydrogen peroxide. Compared with heparin products, it has better antith...

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 周霞雷晓刚乔德强
Owner 山东辰龙药业有限公司
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