CN103864958A - Method of preparing high-purity heparin sodium - Google Patents
Method of preparing high-purity heparin sodium Download PDFInfo
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- CN103864958A CN103864958A CN201310625500.XA CN201310625500A CN103864958A CN 103864958 A CN103864958 A CN 103864958A CN 201310625500 A CN201310625500 A CN 201310625500A CN 103864958 A CN103864958 A CN 103864958A
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- heparin sodium
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- purity heparin
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Abstract
The invention discloses a method of preparing high-purity heparin sodium. The method is characterized in that under a room temperature of 298K, an organic precipitation method is adopted to remove heparin sodium-like impurities dermatan sulfate and chondroitin sulfate in the heparin sodium to prepare high-purity heparin sodium, so that the heparin sodium and similar substances thereof are separated according to solubility difference in different polar solvents. The method is suitable for purifying and separating the sodium-like impurities dermatan sulfate, chondroitin sulfate and the like in the heparin sodium to prepare the high-purity heparin sodium, and has remarkable social and beneficial benefits.
Description
Technical field
The present invention relates to biological technical field, relate in particular to a kind of method of preparing high purity heparin sodium.
Background technology
Heparin sodium and quasi-heparin substance chondroitin sulfate (CS), dermatan sulfate (DS) all belong to the mixture of mucopolysaccharide family macromolecule, the extraction of polysaccharide separates the technique of great majority employing water extract-alcohol precipitation, alcohol precipitation is different according to the molecular size range of polysaccharide, and carry out separation and purification, so when organic solvent deposit, the product difference that volume fraction difference obtains, according to the molecular weight difference of heparin sodium, CS, DS, precipitate to separate impurity CS, the DS in heparin sodium by distribution with organic solvent.
In existing isolation technique, the ion-exchange-resin process that separated to heparin sodium with similar substance CS, DS, its weak point is: take time and effort, expend reagent, complicated operation, yield are low.
For the deficiency of above-mentioned isolation technique, expend reagent in order to solve existing ion-exchange-resin process, take time and effort, the problems such as complicated operation, the invention provides one can sharp separation heparin sodium and similar substance thereof, prepares the method for high purity heparin sodium, method green non-pollution of the present invention, simple, can effectively separate heparin sodium and similar substance thereof, prepare high purity heparin sodium.
Summary of the invention
The present invention is achieved by the following technical solutions:
Prepare a method for high purity heparin sodium, according to heparin sodium and similar substance thereof, the different solubility in the organic solvent of opposed polarity reaches the separation and purification of heparin sodium and its impurity, thereby prepares highly purified heparin sodium:
Described experimental procedure is as follows:
1, take 5g heparin industry crude product (containing DS, the CS impurity of different amounts),
2, add the salt solution that contains certain percentage ratio to be uniformly dissolved,
3, be V1-V2 (Volume) to adding organic solvent volume multiple in solution,
4, evenly, normal temperature leaves standstill to be preserved for some time in vibration,
5, centrifugal, collecting precipitation, then supernatant liquor is regulated to organic solvent volume multiple is V3-V4, evenly, normal temperature leaves standstill to be preserved in vibration,
6, centrifugal, collecting precipitation, then regulate alcohol volume multiple to be V5-V6 supernatant liquor, centrifugal, collecting precipitation, dries the throw out of every part, weighs.
The concentration of the salt in described step 2 is 2%; Organic solvent in described step 3 is ethanol; Organic solvent volume fraction V1 in described step 3 is that 9.1%, V2 is 28.6%; Time of repose in described step 4 is 2 hours; Organic solvent volume fraction V3 in described step 5 is that 33.3%, V4 is 44.4%; Organic solvent volume fraction V5 in described step 6 is that 47.4%, V6 is 66.7%.
The inventive method is simple, is suitable for heparin sodium and similar substance chondroitin sulfate thereof, dermatan sulfate to carry out the free of contamination separation of quick nondestructive, provides technical support for preparing highly purified heparin sodium.
Brief description of the drawings
Fig. 1 is that percent by volume taking ethanol is as X-coordinate, to precipitate the experimental result picture of quality for the substep ethanol precipitation that ordinate zou was done
Embodiment
Below in conjunction with embodiment, the present invention is further illustrated.
Embodiment 1:
(1) take 5g heparin industry crude product (containing DS, the CS impurity of different amounts);
(2) add and contain 2% salt solution and be uniformly dissolved;
(3) be 9.1%-28.6% (Volume) to adding organic solvent volume multiple in solution;
(4) evenly, normal temperature leaves standstill 2 hours in vibration;
(5) centrifugal, collecting precipitation, then supernatant liquor is regulated to organic solvent volume multiple is 33.3%-44.4%, evenly, normal temperature leaves standstill to be preserved in vibration;
(6) centrifugal, collecting precipitation, then regulate alcohol volume multiple to be 47.4%-66.7% supernatant liquor, centrifugal, collecting precipitation, dries the throw out of every part, weighs.
(7) experimental result of ethanol substep alcohol precipitation is in table 1.
Table 1 ethanol substep alcohol precipitation experimental result
Can find out from Fig. 1 (seeing Figure of description) and associative list 1, the quality product of ethanol fractional precipitation heparin industry crude product gained has three sections: the first section volume fraction of ethanol 10% to 33%, this section precipitation quality maximum, its yield accounts for approximately 62.3% of total mass; The second section volume fraction of ethanol 35% to 47%, the quality of this section precipitation is taken second place, and its yield accounts for 24.2% of total mass; Mass ratio two sections of the 3rd section volume fraction of ethanol from 50% to 62% this section precipitation reduce, and its yield accounts for 12.3%.
From
1the qualitative analysis of H-NMR result is known: HP concentrates on the first section, be that ethanol volume multiple 0.1V-0.4V (9.1%-28.6%) is settled out HP, DS concentrates on the second section, be that ethanol volume multiple 0.5V-0.8V (33.3%-44.4%) is settled out DS, CS concentrates on the 3rd section, and ethanol volume multiple 0.9V-2.0V (47.4%-66.7%) is settled out CS.
Claims (7)
1. prepare the method for high purity heparin sodium for one kind, it is characterized in that, step is as follows: according to heparin sodium and similar substance thereof, the different solubility in the organic solvent of opposed polarity reaches the separation and purification of heparin sodium and its impurity, thereby prepares highly purified heparin sodium:
Described experimental procedure is as follows:
(1) take 5g heparin industry crude product (containing DS, the CS impurity of different amounts),
(2) add the salt solution that contains certain percentage ratio to be uniformly dissolved,
(3) be V1-V2 (Volume) to adding organic solvent volume multiple in solution,
(4) evenly, normal temperature leaves standstill to be preserved for some time in vibration,
(5) centrifugal, collecting precipitation, then supernatant liquor is regulated to organic solvent volume multiple is V3-V4, evenly, normal temperature leaves standstill to be preserved in vibration,
(6) centrifugal, collecting precipitation, then regulate alcohol volume multiple to be V5-V6 supernatant liquor, centrifugal, collecting precipitation, dries the throw out of every part, weighs.
2. a kind of method of preparing high purity heparin sodium according to claim 1, is characterized in that: the concentration of salt solution used is 2%.
3. a kind of method of preparing high purity heparin sodium according to claim 1, is characterized in that: organic solvent used is ethanol.
4. a kind of method of preparing high purity heparin sodium according to claim 1, is characterized in that: organic solvent volume fraction V1 used is that 9.1%, V2 is 28.6%.
5. a kind of method of preparing high purity heparin sodium according to claim 1, is characterized in that: organic solvent volume fraction V3 used is that 33.3%, V4 is 44.4%.
6. a kind of method of preparing high purity heparin sodium according to claim 1, is characterized in that: the standing time of normal temperature is 2 hours.
7. a kind of method of preparing high purity heparin sodium according to claim 1, is characterized in that: organic solvent volume fraction V5 used is that 47.4%, V6 is 66.7%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310625500.XA CN103864958A (en) | 2013-11-24 | 2013-11-24 | Method of preparing high-purity heparin sodium |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310625500.XA CN103864958A (en) | 2013-11-24 | 2013-11-24 | Method of preparing high-purity heparin sodium |
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| CN103864958A true CN103864958A (en) | 2014-06-18 |
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| CN201310625500.XA Pending CN103864958A (en) | 2013-11-24 | 2013-11-24 | Method of preparing high-purity heparin sodium |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104163878A (en) * | 2014-08-13 | 2014-11-26 | 南京健友生化制药股份有限公司 | Method for producing nadroparin calcium from heparin sodium crude product |
| CN104448044A (en) * | 2014-12-24 | 2015-03-25 | 南京健友生化制药股份有限公司 | Method for decolorizing heparin sodium and lowering dermatan sulfate content |
| CN104479048A (en) * | 2014-12-24 | 2015-04-01 | 青岛九龙生物医药有限公司 | Method for removing heparinoid impurities such as DS (dermatan sulfate) and the like in heparin sodium |
| CN104530257A (en) * | 2014-12-24 | 2015-04-22 | 青岛九龙生物医药有限公司 | Method for separating dermatan sulfate in heparin sodium |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080318328A1 (en) * | 2004-03-24 | 2008-12-25 | Aventis Pharma S.A. | Process for oxidizing unfractionated heparins and detecting presence or absence of glycoserine in heparin and heparin products |
| CN101824098A (en) * | 2010-02-12 | 2010-09-08 | 淮安麦德森化学有限公司 | Method for quickly precipitating and separating oversulfated chondroitin sulfate in sodium heparin |
| CN102633906A (en) * | 2011-04-11 | 2012-08-15 | 南通天龙畜产品有限公司 | Method for removing oversulfated chondroitin sulfate in production process of crude product heparin sodium |
-
2013
- 2013-11-24 CN CN201310625500.XA patent/CN103864958A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080318328A1 (en) * | 2004-03-24 | 2008-12-25 | Aventis Pharma S.A. | Process for oxidizing unfractionated heparins and detecting presence or absence of glycoserine in heparin and heparin products |
| CN101824098A (en) * | 2010-02-12 | 2010-09-08 | 淮安麦德森化学有限公司 | Method for quickly precipitating and separating oversulfated chondroitin sulfate in sodium heparin |
| CN102633906A (en) * | 2011-04-11 | 2012-08-15 | 南通天龙畜产品有限公司 | Method for removing oversulfated chondroitin sulfate in production process of crude product heparin sodium |
Non-Patent Citations (1)
| Title |
|---|
| 高晓明: "肝素钠中主要杂质的NMR定量分析方法及污染肝素的分离技术研究", 《中国优秀硕士学位论文全文数据库》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104163878A (en) * | 2014-08-13 | 2014-11-26 | 南京健友生化制药股份有限公司 | Method for producing nadroparin calcium from heparin sodium crude product |
| CN104448044A (en) * | 2014-12-24 | 2015-03-25 | 南京健友生化制药股份有限公司 | Method for decolorizing heparin sodium and lowering dermatan sulfate content |
| CN104479048A (en) * | 2014-12-24 | 2015-04-01 | 青岛九龙生物医药有限公司 | Method for removing heparinoid impurities such as DS (dermatan sulfate) and the like in heparin sodium |
| CN104530257A (en) * | 2014-12-24 | 2015-04-22 | 青岛九龙生物医药有限公司 | Method for separating dermatan sulfate in heparin sodium |
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Application publication date: 20140618 |