CN101649008A - Process for producing low molecular sodium heparin - Google Patents
Process for producing low molecular sodium heparin Download PDFInfo
- Publication number
- CN101649008A CN101649008A CN200810147895A CN200810147895A CN101649008A CN 101649008 A CN101649008 A CN 101649008A CN 200810147895 A CN200810147895 A CN 200810147895A CN 200810147895 A CN200810147895 A CN 200810147895A CN 101649008 A CN101649008 A CN 101649008A
- Authority
- CN
- China
- Prior art keywords
- heparin
- low molecular
- sodium
- sodium heparin
- crude
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention discloses a process for producing low molecular sodium heparin by using raw sodium heparin as a raw material, which comprises the steps of: producing a sodium heparin solution; degradingthe solution; neutralizing the solution; collecting a precipitation; producing low molecular raw sodium heparin; producing low molecular fine sodium heparin and the like. The low molecular sodium heparin has the characteristics of rich sources of the raw material, high yield, stable and reliable quality, high purity, low cost, long curative effect, no toxic or side effect, simple process, convenient operation and no 'three wastes' discharge, has the effects of coagulation resistance, thrombosis resistance, tumor resistance, inflammation resistance, allergy resistance and the like and the efficiency of regulating blood lipid, has significant curative effect and wide application range, can be produced into injections, capsules, ointments and the like, is convenient for massive production, and is widely used for producing coagulation resistant low molecular sodium heparin.
Description
Technical field
The present invention relates to a kind of production technique of biologics, particularly relate to a kind of production technique that crude heparin sodium is prepared into the low molecular sodium heparin elaboration.
Background technology
Heparin sodium is the general designation of the cluster acidic mucopolysaccharide mixture of molecular weight different sizes, and its molecular-weight average is 15000D, often with Calciparine/sodium salt and calcium salt as medicinal.It has multiple biological functions such as anti-freezing, antithrombotic, anti-inflammatory, antianaphylaxis, antiviral and reducing blood-fat, also is a kind of active drug of preventing and treating dvt, pulmonary infarction or other thrombus simultaneously.But heparin sodium when clinical application with hemorrhage, thrombopenia, side effects such as osteoporosis, sometimes even can cause that lethality intracranials hemorrhage.In order to alleviate the side effect of heparin sodium, people develop the heparin sodium that molecular-weight average is 5000D by fair means or foul, and this low molecular sodium heparin has that anti thrombotic action is strong, hemorrhage side effect is little, long half time, good medicinal rerum naturas such as bioavailability height.At present, the technology of producing low molecular sodium heparin with heparin sodium crude has three kinds, i.e. physical partition method, chemical cracking method and synthesis method.Physical partition method is mainly used in structure determination and bioactive research, and synthesis method is mainly used in research now, can't be applied to industrial production.Used chemical cracking method of industrial production and zymochemistry cracking process mainly contain the peroxide degradation method, and heparinase edman degradation Edman and B eliminate edman degradation Edman etc.But the production cycle of these chemical cracking methods is long, and the product yield is low has only 80-85%, complex process, quality instability.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, the production technique of a kind of product yield height, the reliable low molecular sodium heparin of steady quality is provided.
Purpose of the present invention is realized by following technical scheme:
A kind of production technique of low molecular sodium heparin may further comprise the steps:
1. make heparin sodium aqua
Add acetate and the 5-8 distilled water doubly of the 0.8-1.2% of its weight in crude heparin sodium, stirred 6-8 hour, the temperature of distilled water is 60 ℃;
2. make degradation solution
Add weight and be 2% Sodium Nitrite of crude heparin sodium in the heparin sodium aqua that 1. step obtains, temperature is-5～30 ℃, stirs 4-5 hour;
3. make neutralizer
In the degradation solution that 2. step obtains, add sodium hydroxide, transfer PH to 6.5-7.0;
4. collecting precipitation thing
Adding weight in the neutralizer that 3. step obtains is 2.5 times ethanol of crude heparin sodium, precipitation collecting precipitation thing;
5. make the low molecular sodium heparin crude product
In the throw out that 4. step obtains, add weight and be 30% acetone of crude heparin sodium, dehydration, drying;
6. make the Low molecular heparin elaboration
The low molecular sodium heparin crude product that 5. step is obtained carries out gel-filtration, just obtains the low molecular sodium heparin elaboration, handles obtaining the low molecular sodium heparin elaboration through sterilization and disinfection.
The weight of described acetate is 1% of crude heparin sodium.
The present invention compared with prior art has the following advantages:
1, raw material of substance crude heparin sodium of the present invention is originated and is enriched, and produces yield up to 95%, and steady quality is reliable, the purity height, and cost is low, and curative effect reaches 24 hours, has no side effect, and can be made into injection, capsule and paste etc.
2, technology is simple, and is easy to operate, do not have " three wastes " discharging, meets the policy of country's " energy-saving and emission-reduction ";
3, product molecular-weight average of the present invention is 4000-8000D, and it is evident in efficacy, and pharmacological action is strong, and use range is wide, has the effect of effects such as anticoagulation, antithrombotic, antitumor, anti-inflammatory, antianaphylaxis and regulating blood fat.
Embodiment
Come further to set forth the present invention by the following examples.
Embodiment 1:
The production technique of low molecular sodium heparin of the present invention may further comprise the steps:
1. make heparin sodium aqua
Take by weighing crude heparin sodium 10kg and put into reactor, add the acetate of 0.1kg and the distilled water of 70kg, stirred 6-8 hour, the temperature of distilled water is 60 ℃;
2. make degradation solution
Add the Sodium Nitrite of 0.2kg in the heparin sodium aqua that 1. step obtains, temperature is-5～30 ℃, stirs 4-5 hour;
3. make neutralizer
In the degradation solution that 2. step obtains, add sodium hydroxide, transfer PH to 6.5-7.0;
4. collecting precipitation thing
The ethanol that in the neutralizer that 3. step obtains, adds 25kg, precipitation collecting precipitation thing;
5. make the low molecular sodium heparin crude product
In the throw out that 4. step obtains, add 3kg acetone, dehydration, drying;
6. make the Low molecular heparin elaboration
The low molecular sodium heparin crude product that 5. step is obtained carries out gel-filtration, just obtains 9.5kg low molecular sodium heparin elaboration, handles obtaining the low molecular sodium heparin elaboration through sterilization and disinfection, can be made into injection, capsule and paste etc.
Through check, the leading indicator of product is: anticoagulant efficiency, and tiring of every 1mg is 157 units; Heavy metal＜30ug/kg; Specific optical rotation+49 °, absorbancy and every medicine inspection, physical and chemical index reach the Chinese Pharmacopoeia standard.
Claims (2)
1, a kind of production technique of low molecular sodium heparin is characterized in that: may further comprise the steps:
1. make heparin sodium aqua
Add acetate and the 5-8 distilled water doubly of the 0.8-1.2% of its weight in crude heparin sodium, stirred 6-8 hour, the temperature of distilled water is 60 ℃;
2. make degradation solution
Add weight and be 2% Sodium Nitrite of crude heparin sodium in the heparin sodium aqua that 1. step obtains, temperature is-5～30 ℃, stirs 4-5 hour;
3. make neutralizer
In the degradation solution that 2. step obtains, add sodium hydroxide, transfer PH to 6.5-7.0;
4. collecting precipitation thing
Adding weight in the neutralizer that 3. step obtains is 2.5 times ethanol of crude heparin sodium, precipitation, collecting precipitation thing;
5. make the low molecular sodium heparin crude product
In the throw out that 4. step obtains, add weight and be 30% acetone of crude heparin sodium, dehydration, drying;
6. make the Low molecular heparin elaboration
The low molecular sodium heparin crude product that 5. step is obtained carries out gel-filtration, just obtains the low molecular sodium heparin elaboration, handles obtaining the low molecular sodium heparin elaboration through sterilization and disinfection.
2, the production technique of low molecular sodium heparin according to claim 1 is characterized in that: the weight of described acetate is 1% of crude heparin sodium.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810147895A CN101649008A (en) | 2008-12-17 | 2008-12-17 | Process for producing low molecular sodium heparin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810147895A CN101649008A (en) | 2008-12-17 | 2008-12-17 | Process for producing low molecular sodium heparin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101649008A true CN101649008A (en) | 2010-02-17 |
Family
ID=41671350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810147895A Pending CN101649008A (en) | 2008-12-17 | 2008-12-17 | Process for producing low molecular sodium heparin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101649008A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102464804A (en) * | 2010-11-14 | 2012-05-23 | 四川天成生化科技有限公司 | Sodium heparin biological decomposition agent |
| CN103059165A (en) * | 2012-12-26 | 2013-04-24 | 蚌埠丰原涂山制药有限公司 | Polysaccharide acylate and preparation method thereof |
-
2008
- 2008-12-17 CN CN200810147895A patent/CN101649008A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102464804A (en) * | 2010-11-14 | 2012-05-23 | 四川天成生化科技有限公司 | Sodium heparin biological decomposition agent |
| CN102464804B (en) * | 2010-11-14 | 2016-05-18 | 四川天成生化科技有限公司 | Sodium heparin biological decomposition agent |
| CN103059165A (en) * | 2012-12-26 | 2013-04-24 | 蚌埠丰原涂山制药有限公司 | Polysaccharide acylate and preparation method thereof |
| CN103059165B (en) * | 2012-12-26 | 2015-04-29 | 安徽丰原药业股份有限公司 | Polysaccharide acylate and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4709203B2 (en) | Argin oligosaccharide and its derivatives, and their preparation and use | |
| CN102558393B (en) | Preparation process of dalteparin sodium | |
| CN1844165A (en) | Process for preparing high purity sodium heparin by purification of crude sodium heparin | |
| CN101649008A (en) | Process for producing low molecular sodium heparin | |
| Pan et al. | Ultrasonic-assisted extraction process of crude polysaccharides from Yunzhi mushroom and its effect on hydroxyproline and glycosaminoglycan levels | |
| CN102153676B (en) | Method for removing organic residue in heparin sodium through vacuum drying | |
| CN103012609A (en) | Method for extracting fucosan sulphate from sea cucumber cooking waste liquor | |
| JPS5920302A (en) | Manufacture of low molecular heparin fraction | |
| CN101328225A (en) | Sulfuric acid rhamnosan, preparation and use thereof | |
| US20100075922A1 (en) | Heparins including at least one covalent bond with biotin or a biotin derivative, method for preparing same and use thereof | |
| CN110551233A (en) | Callicarpa kwangtungensis polysaccharide and extraction method and application thereof | |
| JP2005530877A (en) | Low molecular weight persulfated polysaccharide | |
| CN110746287B (en) | Synthesis method of prasugrel intermediate o-fluorophenylacetic acid | |
| CN113754788A (en) | Sargassum pallidum fucosan and preparation method and application thereof | |
| CN1421464A (en) | Low molecular weight heparine sodium (calcium) and its prepn | |
| JP5153324B2 (en) | Hard tissue formation promoter | |
| Shi et al. | Study on the antibacterialactivity of Bergenia purpurascens extract | |
| CN110872361A (en) | Glucosamine chondroitin sulfate, preparation method and application | |
| Yuan et al. | Corrigendum to" The gut microbes in inflammatory bowel disease: Future novel target option for pharmacotherapy" Biomed. Pharmacother. 165 (2023) 114893 | |
| CN113292532B (en) | Polysubstituted naphthoquinone derivative and preparation method and application thereof | |
| Zhiqiang et al. | Coordination of copper with aspirin improves its anti-inflammatory activity | |
| CN103665193A (en) | Method for improving titer of heparin sodium | |
| CN103040831B (en) | Application of multi-substituted piperazinyl pyranone in preparation of fungal infection resisting drugs | |
| JP2000128796A (en) | Hemostatic | |
| CN117510655A (en) | Polymannan for inhibiting formation of bacterial biofilm and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Open date: 20100217 |