CN103044576B - Method for improving stability of heparin sodium - Google Patents

Abstract

The invention relates to a technical method for improving stability of heparin sodium. At present, a hydrogen peroxide oxidizing method is generally used for decoloring in a heparin sodium refining process; the prepared heparin sodium product contains residual peroxy ions (O22-); the stability of the product is affected in the heparin sodium storage process; and the biological value of the product is reduced. The method for improving the stability of the heparin sodium, provided by the invention, has the advantages as follows: through the adoption of a low temperature reduction method, residual oxygen ions generated in the refining process are removed and the product stability is improved.

Description

A kind of method improving stability of heparin sodium

Technical field

The present invention relates to a kind of raising stability of heparin sodium method, particularly a kind of heparin sodium production process.

Background technology

Heparin sodium is a kind of clinical conventional anticoagulation medicine, the mucopolysaccharide material mainly extracted from pig intestinal mucosa, has anticoagulation and prevent thrombotic effect significantly.The emerging in large numbers of low molecular sodium heparin product in recent years, makes the application of heparin sodium more and more extensive.Current heparin sodium industry is generally applied hydrogen peroxide oxidation process and is refined, and this technique comparatively potassium permanganate oxidation has sent out plurality of advantages, and technique is simple, and oxidation efficiency is high.But be also faced with the residue problem of peroxide radical ion simultaneously, bring challenges to the stability of heparin sodium.

Summary of the invention

Object of the present invention provides a kind of reductive agent to remove the method for residual oxygen radical ion in refining heparin sodium, overcomes the stability problem that hydrogen peroxide oxidation method for refining brings.

Object of the present invention reaches by the following technical programs, is realized successively by following step.

1, the heparin sodium refining through hydrogen peroxide is dropped in retort, dissolve in the ratio purified water of 1: 10 (w/w);

2, be cooled to 10-15 DEG C, adjust pH=9.0-10.0, add reductive agent A or reductive agent B in the ratio of 3-5%, insulation leaves standstill 10-12 hour;

3, feed liquid is filtered;

4, by the feed liquid after filtration, regulate pH=5.0-5.5, add sodium-chlor by 2-4% (w/v), adding 95% ethanol to alcohol concn is afterwards 38-45%, leaves standstill 10-12 hour, throw out dehydration post-drying.

The beneficial effect of the technical program is: the stability of heparin sodium product can be evaluated by accelerated test and long-term stable experiment data.The inventive method product through 6 months accelerated tests (temperature 40 ± 2 DEG C, relative humidity 75 ± 5%), titer of heparin sodium reduction≤2U/mg; Through 2 years long-term stable experiments, titer of heparin sodium reduction≤3U/mg.Without the obtained product of the traditional method of reduction through 6 months accelerated tests (temperature 40 ± 2 DEG C, relative humidity 75 ± 5%), titer of heparin sodium reduction >=6U/mg; Through 2 years long-term stable experiments, titer of heparin sodium reduction >=10U/mg, contrast was as following table.

The first, in the technical program, adding the temperature before reductive agent must be down to 10-15 DEG C, reflection mild condition.

The second, in the technical program, reductive agent A is V-Brite B, after diluting with gac or talcum powder, reduction reaction gentleness can be made to carry out.

3rd, in the technical program, reductive agent B is Sulfothiorine, after diluting with gac or talcum powder, reduction reaction gentleness can be made to carry out.

Embodiment

Following instance describes the present invention in detail:

1, by the heparin sodium 50Kg through hydrogen peroxide oxide purification, join in retort, add 500Kg purified water and fully dissolve.

2, be cooled to 15 DEG C, regulate pH=9.5, add reductive agent A22g (11g V-Brite B fully mixes with 11g gac), after stirring, stand at low temperature 10-12 hour.

3, feed liquid filter press device is filtered (millipore filtration aperture is 0.8 μm).

4, by the feed adjustment pH=5.0 after filtering, adding 16.5Kg sodium-chlor, is 40% with 95% alcohol settling to alcohol concn afterwards, leaves standstill 10 hours, and post-drying of dewatering, must have good stability heparin sodium.

Claims (1)

1. improve a method for stability of heparin sodium, it is characterized in that:

(1) heparin sodium refining through hydrogen peroxide is dropped in retort, dissolve by the mass ratio purified water of 1: 10;

(2) be cooled to 10-15 DEG C, adjust pH=9.0-10.0, add reductive agent A or reductive agent B in the ratio of 3-5%, insulation leaves standstill 10-12 hour;

(3) feed liquid is filtered;

(4) by the feed liquid after filtration, regulate pH=5.0-5.5, add sodium-chlor by 2-4% (w/v), adding 95% ethanol to alcohol concn is afterwards 38-45%, leaves standstill 10-12 hour, throw out dehydration post-drying;

Reductive agent A is V-Brite B and gac or V-Brite B and talcous mixture;

Reductive agent B is Sulfothiorine and gac or Sulfothiorine and talcous mixture;

Feed liquid is filtered into filters with filter press device, millipore filtration aperture≤0.8 μm.