CN103044576A - Method for improving stability of heparin sodium - Google Patents
Method for improving stability of heparin sodium Download PDFInfo
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- CN103044576A CN103044576A CN2012105497399A CN201210549739A CN103044576A CN 103044576 A CN103044576 A CN 103044576A CN 2012105497399 A CN2012105497399 A CN 2012105497399A CN 201210549739 A CN201210549739 A CN 201210549739A CN 103044576 A CN103044576 A CN 103044576A
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- heparin sodium
- stability
- reductive agent
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- feed liquid
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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
Technical field
The present invention relates to a kind of raising heparin sodium stability approach, particularly a kind of heparin sodium production process.
Background technology
Heparin sodium is a kind of clinical anticoagulation medicine commonly used, and the mucopolysaccharide material that mainly extracts from pig intestinal mucosa has significantly anticoagulation and prevents thrombotic effect.Emerging in large numbers of low molecular sodium heparin product makes the application of heparin sodium more and more extensive in recent years.It is refining that present heparin sodium industry is generally used hydrogen peroxide oxidation process, and this technique has been sent out plurality of advantages than potassium permanganate oxidation, and technique is simple, and oxidation efficiency is high.But also be faced with the residue problem of peroxide radical ion simultaneously, bring challenges for the stability of heparin sodium.
Summary of the invention
Purpose of the present invention provides a kind of reductive agent to remove the method for residual oxygen radical ion in the refining heparin sodium, has overcome the stability problem that the hydrogen peroxide oxidation method for refining brings.
Purpose of the present invention reaches by the following technical programs, realizes by following step successively.
1, will drop in the retort through the refining heparin sodium of hydrogen peroxide, dissolve with purified water in the ratio of 1: 10 (w/w);
2, be cooled to 10-15 ℃, transfer pH=9.0-10.0, in ratio adding reductive agent A or the reductive agent B of 3-5%, insulation was left standstill 10-12 hour;
3, feed liquid is filtered;
4, the feed liquid after will filtering is regulated pH=5.0-5.5, press 2-4% (w/v) and adds sodium-chlor, and adding afterwards 95% ethanol to alcohol concn is 38-45%, leaves standstill 10-12 hour, and the throw out post-drying of dewatering gets final product.
The beneficial effect of the technical program is: the stability of heparin sodium product can be estimated with accelerated test and long-term stable experiment data.The inventive method product is through 6 months accelerated tests (40 ± 2 ℃ of temperature, relative humidity 75 ± 5%), the heparin sodium reduction≤2U/mg that tires; Through long-term stability test in 2 years, the heparin sodium reduction≤3U/mg that tires.Without the product that makes of traditional method of reduction through 6 months accelerated tests (40 ± 2 ℃ of temperature, relative humidity 75 ± 5%), the heparin sodium reduction 〉=6U/mg that tires; Through long-term stability test in 2 years, the heparin sodium reduction 〉=10U/mg that tires, contrast is such as following table.
The first, in the technical program, add the front temperature of reductive agent and must be down to 10-15 ℃, the reflection mild condition.
The second, in the technical program, reductive agent A is V-Brite B, after diluting with gac or talcum powder, the reduction reaction gentleness is carried out.
The 3rd, in the technical program, reductive agent B is Sulfothiorine, after diluting with gac or talcum powder, the reduction reaction gentleness is carried out.
Embodiment
Following instance describes the present invention in detail:
1, will join in the retort through the heparin sodium 50Kg of hydrogen peroxide oxide purification, add the 500Kg purified water and fully dissolve.
2, be cooled to 15 ℃, regulate pH=9.5, add reductive agent A22g (the 11g V-Brite B fully mixes with the 11g gac), after stirring, stand at low temperature 10-12 hour.
3, feed liquid is filtered (the millipore filtration aperture is 0.8 μ m) with the filter press device.
4, the feed adjustment pH=5.0 after will filtering adds 16.5Kg sodium-chlor, and being precipitated to alcohol concn with 95% ethanol afterwards is 40%, leaves standstill 10 hours, the post-drying of dewatering, and heparin sodium must have good stability.
Claims (4)
1. method that improves heparin sodium stability is characterized in that:
(1) will drop in the retort through the refining heparin sodium of hydrogen peroxide, dissolve with purified water in the ratio of 1: 10 (w/w);
(2) be cooled to 10-15 ℃, transfer pH=9.0-10.0, in ratio adding reductive agent A or the reductive agent B of 3-5%, insulation was left standstill 10-12 hour;
(3) feed liquid is filtered;
(4) feed liquid after will filtering is regulated pH=5.0-5.5, press 2-4% (w/v) and adds sodium-chlor, and adding afterwards 95% ethanol to alcohol concn is 38-45%, leaves standstill 10-12 hour, and the throw out post-drying of dewatering gets final product.
2. according to claims 1 described method, it is characterized by: reductive agent A represents V-Brite B and gac or V-Brite B and talcous mixture.
3. according to claims 1 described method, it is characterized by: reductive agent B represents Sulfothiorine and gac or Sulfothiorine and talcous mixture.
4. according to claims 1 described method, it is characterized by: feed liquid is filtered into the filter press device and filters, millipore filtration aperture≤0.8 μ m.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210549739.9A CN103044576B (en) | 2012-12-07 | 2012-12-07 | Method for improving stability of heparin sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210549739.9A CN103044576B (en) | 2012-12-07 | 2012-12-07 | Method for improving stability of heparin sodium |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103044576A true CN103044576A (en) | 2013-04-17 |
| CN103044576B CN103044576B (en) | 2015-07-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210549739.9A Active CN103044576B (en) | 2012-12-07 | 2012-12-07 | Method for improving stability of heparin sodium |
Country Status (1)
| Country | Link |
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| CN (1) | CN103044576B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114276473A (en) * | 2020-09-27 | 2022-04-05 | 上海帕尼生物科技有限公司 | Refined heparin sodium product and extraction method and application thereof |
-
2012
- 2012-12-07 CN CN201210549739.9A patent/CN103044576B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 张万忠: "肝素精制及低分子量肝素的制备", 《中国优秀硕士学位论文全文数据库（硕士）工程科技I辑》 * |
| 林灿煌，张灿河: "正交试验设计优化脱氧剂配方", 《福建化工》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114276473A (en) * | 2020-09-27 | 2022-04-05 | 上海帕尼生物科技有限公司 | Refined heparin sodium product and extraction method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103044576B (en) | 2015-07-15 |
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Address after: 266100 Zhuzhou Road, Laoshan District, Shandong, No. 97, No. Patentee after: Qingdao Jiulong biological medicine group Co., Ltd. Address before: 266100 Zhuzhou Road, Laoshan District, Shandong, No. 97, No. Patentee before: Qingdao Jiulong Bio-Pharmaceutical Co., Ltd. |