CN103804521A - Method for purifying heparin sodium through rapid temperature rise - Google Patents
Method for purifying heparin sodium through rapid temperature rise Download PDFInfo
- Publication number
- CN103804521A CN103804521A CN201310616542.7A CN201310616542A CN103804521A CN 103804521 A CN103804521 A CN 103804521A CN 201310616542 A CN201310616542 A CN 201310616542A CN 103804521 A CN103804521 A CN 103804521A
- Authority
- CN
- China
- Prior art keywords
- heparin sodium
- solution
- value
- temperature rise
- add
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention discloses a method for purifying heparin sodium through rapid temperature rise, belonging to the technical field of biochemical crude drugs. The novel developed and researched method comprises the following steps of regulating the pH value of a treated crude heparin sodium solution by using a sodium hydroxide solution, and then, rapidly raising the temperature to achieve the aim of purifying crude heparin sodium. The method can be used for effectively removing protein impurities and bacteria and keeping the activity of heparin sodium unchanged. Impurities are removed through rapid temperature rise, so that the method is high in efficiency, simple in operation and capable of greatly reducing the cost.
Description
Technical field
The present invention relates to biological technical field, utilize the warm method that rises suddenly to reach the object of purified heparin sodium crude product, the environment of recycling ethanol and highly basic, makes purifying more complete, reaches the effect that improves purifying rate.
Background technology
Heparin is Mike's human relations in 1919 in the time of research blood coagulation, the natural bioactive mucopolysaccharide material of finding from the liver of dog.After more than ten years, just discovery and extraction from ox lung of European and American developed countries, then found again afterwards that in pig, sheep small intestine mucous membrane, content was very abundant, and start to carry out medical clinical study.Within 1940, heparin is formally listed American Pharmacopeia in, and is widely used in anticoagulation, prevents thrombosis, treatment cardiovascular and cerebrovascular diseases etc.China starts to introduce production the seventies, existing nearly 40 years so far historical.Existing market supply be mainly the crude heparin sodium extracting from pig intestinal mucosa or animal lungs.In leaching process, because heparin dissociates not exclusively, make always to exist in crude product heparin the protein of some amount, can not be directly used in pharmacy or outlet, therefore need to be further purified exquisiteness.Heparin sodium after exquisiteness is generally subject to the attention of countries in the world the world of medicine as anticoagulation material medicine, be also simultaneously one of China's export main biochemical products of earning foreign exchange.
Pig intestinal mucosa heparin is the biochemical drug of the important outlet of China, but the defects such as the heparin product of producing at present exists, and purity is low, extraction yield is low, environmental pollution is large, do not meet standards of pharmacopoeia, product toxic side effect is large, activity is low, great majority are to exist with the form of crude product heparin, and in refined heparin sodium preparation, the removal protein that China is existing and the mode of bacterium are mainly to acid adding in solution and reduce pH value and interpolation fungistat.But aforesaid method changes greatly pH, not only reduces heparin sodium activity, and follow-up still need regulate pH value, makes production process more loaded down with trivial details, increases cost.
Summary of the invention
The present invention is to provide a kind of preparation method of high purity heparin sodium, highlighted the keying action that the warm link that rises suddenly plays whole technique, by the temperature that rises suddenly, impurity and bacterium can be removed preferably, and shortened activity time, reduced cost.
The concrete grammar of the warm therapy purified heparin sodium that rises suddenly that the present invention proposes, comprises the following steps:
1, be the hydrochloric acid conditioning solution pH to 6-8 of 18-22% to adding volumetric concentration in heparin sodium crude solution, be warming up to after 45-48 ℃, add the pancreatin of 10-20g/ hundred million units.
2, after being incubated 2-4 hour, then adjust pH to 10-12 with the sodium hydroxide solution of volumetric concentration 30-35%, be suddenly warming up to 83-95 ℃, leave standstill about 10-15 minute, open stirring, pass into circulating water cooling, be cooled to 50-55 ℃.
3, the 10-20% ethanol that adds liquor capacity, stirs, and in the time that temperature is down to 45-55 ℃, adjusts pH to 10-12 with the sodium hydroxide solution of volumetric concentration 30-35%, and static layering is spent the night, sedimentation and filtration.
Embodiment
Embodiment 1
1, be the hydrochloric acid conditioning solution pH to 6-8 of 18-22% to adding volumetric concentration in heparin sodium crude solution, be warming up to after 45-48 ℃, add the pancreatin of 10-20g/ hundred million units.
2, after being incubated 2-4 hour, then adjust pH to 10-12 with the sodium hydroxide solution of volumetric concentration 30-35%, be suddenly warming up to 83-95 ℃, leave standstill about 10-15 minute, open stirring, pass into circulating water cooling, be cooled to 50-55 ℃.
3, the 10-20% ethanol that adds liquor capacity, stirs, and in the time that temperature is down to 45-55 ℃, adjusts pH to 10-12 with the sodium hydroxide solution of volumetric concentration 30-35%, and static layering is spent the night, sedimentation and filtration.
Claims (8)
1. a method for the warm therapy that rises suddenly purified heparin sodium, comprises the following steps:
(1) in crude heparin sodium solution, add hydrochloric acid conditioning solution pH value, after intensification, add pancreatin
(2) regulate pH value with sodium hydroxide solution, the temperature that rises suddenly, leaves standstill 10-15 minute, opens stirring, passes into recirculated water, cooling.
(3) add ethanol, stir, use sodium hydroxide solution adjust pH, hold over night, precipitation.
2. method according to claim 1, is characterized by: in step (1), adding volume ratio is the hydrochloric acid of 18-22%.
3. method according to claim 1, is characterized by: in step (1), the pH value of regulator solution is to 6-8.
4. method according to claim 1, is characterized by: in step (2), adding volume ratio is the sodium hydroxide of 30-35%.
5. method according to claim 1, is characterized by: in step (2), the pH of regulator solution is to 10-12.
6. method according to claim 1, is characterized by: in step (2), the temperature that the temperature that rises suddenly reaches is 83-95 ℃.
7. method according to claim 1, is characterized by: in step (3), add the ethanol of liquor capacity 10-20%.
8. method according to claim 1, is characterized by: in step (3), regulator solution pH value reaches 10-12.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310616542.7A CN103804521A (en) | 2013-11-22 | 2013-11-22 | Method for purifying heparin sodium through rapid temperature rise |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310616542.7A CN103804521A (en) | 2013-11-22 | 2013-11-22 | Method for purifying heparin sodium through rapid temperature rise |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103804521A true CN103804521A (en) | 2014-05-21 |
Family
ID=50701949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310616542.7A Pending CN103804521A (en) | 2013-11-22 | 2013-11-22 | Method for purifying heparin sodium through rapid temperature rise |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103804521A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101575385A (en) * | 2008-05-09 | 2009-11-11 | 青岛九龙生物医药有限公司 | Method for separating chondroitin polysulfate from heparin sodium by extraction method |
| CN101824099A (en) * | 2010-02-12 | 2010-09-08 | 淮安麦德森化学有限公司 | Method for purifying crude product heparin sodium |
| CN103030715A (en) * | 2012-12-07 | 2013-04-10 | 青岛九龙生物医药有限公司 | Method for separating purified heparin sodium |
| CN103044578A (en) * | 2012-12-07 | 2013-04-17 | 青岛九龙生物医药有限公司 | Efficient method for refining heparin sodium crude products |
-
2013
- 2013-11-22 CN CN201310616542.7A patent/CN103804521A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101575385A (en) * | 2008-05-09 | 2009-11-11 | 青岛九龙生物医药有限公司 | Method for separating chondroitin polysulfate from heparin sodium by extraction method |
| CN101824099A (en) * | 2010-02-12 | 2010-09-08 | 淮安麦德森化学有限公司 | Method for purifying crude product heparin sodium |
| CN103030715A (en) * | 2012-12-07 | 2013-04-10 | 青岛九龙生物医药有限公司 | Method for separating purified heparin sodium |
| CN103044578A (en) * | 2012-12-07 | 2013-04-17 | 青岛九龙生物医药有限公司 | Efficient method for refining heparin sodium crude products |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101831008B (en) | New production process for refining crude heparin sodium | |
| CN101544999B (en) | Method for producing and purifying high purity and low molecular weight sodium heparin | |
| CN105018555A (en) | Preparation method of giant salamander skin collagen peptide | |
| CN101735340A (en) | Method for preparing heparin sodium by combining enzymolysis and salt decomposition | |
| CN104031170B (en) | A kind of people dextran iron material used for intravenous injection and preparation method thereof | |
| CN102070727A (en) | Extraction method of sodium heparin | |
| CN107188990A (en) | The method that chondroitin sulfate is extracted in sturgeon bone | |
| CN104357522A (en) | Method for extracting collagen by using ecdysis of giant salamander | |
| CN103044578A (en) | Efficient method for refining heparin sodium crude products | |
| CN103804522B (en) | A kind of method improving heparin sodium purity | |
| CN110144373A (en) | Extract the method for chondroitin sulfate and collagen peptide respectively using animal cartilage | |
| CN104341539A (en) | A one-step preparing method of high-quality heparin sodium by combination of an enzymatic method and a membrane technology | |
| CN112501229A (en) | Production process of bovine bone collagen peptide | |
| CN101768582B (en) | Production process for modifying SOD | |
| CN101779628A (en) | Method for preparing gallic acid aquiculture sanitizer and product thereof | |
| CN106995369A (en) | A kind of preparation method using danshensu as the red sage root extract of object | |
| CN106834399A (en) | A kind of Antihypertensive Peptides from Trachyostracous mussel closed shell flesh | |
| CN103804521A (en) | Method for purifying heparin sodium through rapid temperature rise | |
| CN107163163A (en) | A kind of processing method of chondroitin sulfate product | |
| CN113604532A (en) | Preparation method of yak bone collagen peptide | |
| CN106749758A (en) | Diluted alkaline-enzymolysis-resin adsorption extraction method extracts the chondroitin sulfate in hog snout bone | |
| CN102993335A (en) | Heparin sodium balance extraction method | |
| CN104628889A (en) | Extraction method of heparin sodium | |
| CN105558969A (en) | Formula and preparation process of saussurea involucrata comb honey | |
| CN104130254B (en) | A kind of berberine tannate synthesis technique that reduces unknown impuritie |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140521 |