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Preparation method of novel source of low molecular weight heparin from nitrous acid degradation

A technology of sodium nitrite and heparin sodium, applied in the field of preparation of new sources of nitrous acid to degrade low molecular weight heparin, can solve the problem of single source of species

Inactive Publication Date: 2016-02-03
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention aims at the problem of single source of low-molecular-weight heparin drugs degraded by nitrous acid, and prepares low-molecular-weight heparin by using heparin from a new species source through nitrous acid degradation

Method used

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  • Preparation method of novel source of low molecular weight heparin from nitrous acid degradation

Examples

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preparation example Construction

[0007] The preparation method of nadroparin calcium, the steps are as follows:

[0008] (i) Completely dissolve the heparin sodium prepared from the raw material bovine lung, bovine intestine and / or sheep intestine in water, add sodium nitrite, the heparin sodium is 10 to 30 times the mass of sodium nitrite, adjust the pH to 2 to 5, and react 80 to 120 minutes, then adjust the pH to 9 to 12 to prepare the reaction solution A;

[0009] (ii) Add sodium borohydride to the reaction liquid A prepared in step (i), the sodium borohydride is 1-3% of the mass of heparin sodium, react for 4-8 hours, adjust the pH to 2-5 with hydrochloric acid, mix well , and then adjusted to neutrality with sodium hydroxide to prepare reaction solution B;

[0010] (iii) In the reaction solution B prepared in step (ii), add 3 to 5 times the volume of alcohol, separate the solid and liquid, and dry to obtain solid A, then dissolve solid A in water, the mass of solid A and water The volume ratio is 1: (5...

specific Embodiment approach

[0031] The technical solutions of the present invention will be further described below in conjunction with the examples, but the protection scope of the present invention is not limited thereto.

[0032] The raw material bovine lung described in the embodiment and comparative example, bovine intestine, the heparin sodium prepared by sheep intestine is purified and prepared according to the prior art, can refer to Wang Qingyuan's " heparin sodium process research " (" China Pharmaceutical Industry Journal " 1991 05 phases ) to describe the method to obtain heparin sodium.

Embodiment 1

[0034] Bovine lung derived heparin sodium to prepare nadroparin calcium samples, the steps are as follows:

[0035] (i) Completely dissolve sodium heparin derived from bovine lung in water, add sodium nitrite, the sodium heparin is 30 times the mass of sodium nitrite, adjust the pH to 2.5, react for 80 minutes, and then adjust the pH to 10 to prepare the reaction solution A ;

[0036] (ii) Add sodium borohydride to the reaction solution A prepared in step (i), the mass percentage of sodium borohydride and heparin sodium is 1%, react for 6 hours, adjust the pH to 3 with hydrochloric acid, mix well, and then use hydrogen Sodium oxide was adjusted to neutrality to prepare reaction solution B;

[0037] (iii) In the reaction solution B prepared in step (ii), add 4 times the volume of ethanol, separate the solid from the liquid, and dry to obtain solid A, then dissolve solid A in water, the mass volume ratio of solid A to water The ratio is 1:10, the unit is g / mL, and the reaction...

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Abstract

The invention relates to a preparation method of a novel source of low molecular weight heparin from nitrous acid degradation. The steps are as follows: (I) completely dissolving raw materials in water, adding sodium nitrite to prepare a reaction solution A; (II), adding sodium borohydride, and reacting to prepare a reaction solution B; (III) adding an alcohol solution, conducting solid-liquid separation, drying to prepare a solid A, and then dissolving the solid A in water to prepare a reaction solution C; (IV) replacing sodium ions with calcium ions by cation resin exchange to prepare a reaction solution D; and (V) adding alcohol solution to the reaction solution D, fully mixing, conducting solid-liquid separation, purifying, and drying to prepare the low molecular weight heparin. The invention can fundamentally promote the diversification of species sources for low molecular heparin, expand the supply of raw materials for heparin drugs, and achieve a higher degree of stabilization of the market of heparin and low molecular weight heparin drugs.

Description

technical field [0001] The invention relates to a method for preparing low-molecular-weight heparin degraded by nitrous acid from a new source, in particular to a method for preparing low-molecular-weight heparin by degrading heparin from bovine (bovine lung, bovine intestine) and sheep (sheep intestine) with nitrous acid. It belongs to the technical field of raw material medicine preparation. Background technique [0002] Heparin is an anticoagulant clinical drug that can be extracted from the mucosal tissues of various mammals. It was first discovered in the liver of dogs in 1916. Later, in order to obtain high yields, the source was mainly turned to cattle and pigs. However, due to the "mad cow disease" and "sheep scrapie" that broke out in Europe at the end of the last century and were fatally transmitted from cattle and sheep to humans, heparin derived from cattle and sheep was banned, so the raw materials of heparin drugs are currently limited to pigs. Low-molecular-w...

Claims

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Application Information

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IPC IPC(8): C08B37/10
Inventor 迟连利管玉东徐晓晖
Owner SHANDONG UNIV
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