CN100467493C - Producing process for low molecular weight calcium heparin - Google Patents
Producing process for low molecular weight calcium heparin Download PDFInfo
- Publication number
- CN100467493C CN100467493C CNB2007100614766A CN200710061476A CN100467493C CN 100467493 C CN100467493 C CN 100467493C CN B2007100614766 A CNB2007100614766 A CN B2007100614766A CN 200710061476 A CN200710061476 A CN 200710061476A CN 100467493 C CN100467493 C CN 100467493C
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- Prior art keywords
- value
- calcium
- minutes
- heparin
- sodium
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- 229920000669 heparin Polymers 0.000 title claims abstract description 28
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 239000011575 calcium Substances 0.000 title claims abstract description 27
- 229910052791 calcium Inorganic materials 0.000 title claims abstract description 27
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 229960002897 heparin Drugs 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims description 16
- 230000008569 process Effects 0.000 title claims description 9
- 230000001858 anti-Xa Effects 0.000 claims abstract description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 239000007788 liquid Substances 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 15
- 238000001556 precipitation Methods 0.000 claims description 12
- 239000008213 purified water Substances 0.000 claims description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 10
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 claims description 9
- 229960001008 heparin sodium Drugs 0.000 claims description 9
- 238000004108 freeze drying Methods 0.000 claims description 8
- 239000012528 membrane Substances 0.000 claims description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 8
- 239000012279 sodium borohydride Substances 0.000 claims description 8
- 235000010288 sodium nitrite Nutrition 0.000 claims description 8
- 238000005303 weighing Methods 0.000 claims description 8
- 238000000108 ultra-filtration Methods 0.000 claims description 7
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 6
- 239000001110 calcium chloride Substances 0.000 claims description 6
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 102000011759 adducin Human genes 0.000 claims description 5
- 108010076723 adducin Proteins 0.000 claims description 5
- 238000011146 sterile filtration Methods 0.000 claims description 4
- 229940095529 heparin calcium Drugs 0.000 claims description 3
- 239000003055 low molecular weight heparin Substances 0.000 claims description 3
- 238000005374 membrane filtration Methods 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 241000143437 Aciculosporium take Species 0.000 claims description 2
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 claims description 2
- 208000012826 adjustment disease Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000001914 filtration Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 22
- 230000000694 effects Effects 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 5
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000008676 import Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 206010014522 Embolism venous Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000005352 clarification Methods 0.000 description 2
- 238000012691 depolymerization reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 208000004043 venous thromboembolism Diseases 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 208000006193 Pulmonary infarction Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002170 aldosterone antagonist Substances 0.000 description 1
- 229940083712 aldosterone antagonist Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 159000000007 calcium salts Chemical group 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000002682 general surgery Methods 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 150000002832 nitroso derivatives Chemical class 0.000 description 1
- 230000010494 opalescence Effects 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000007575 pulmonary infarction Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
Images
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Handicraft product of the present invention | National standard | The import standard | |
Proterties | Colourless clear liquid | Colourless or faint yellow clear liquid | Clarification or opalescence or faint yellow clear liquid |
The pH value | 4.5~7.5 | 5.5~8.0 | 4.5~7.5 |
Anti-Xa factor is tired | 95-130IU/mg | Be not less than 70IU/mg | 95-130IU/mg |
Xa/IIa | 2.5~4.0 | ≥1.5 | 2.5~4.0 |
Molecular weight | 3600~5000 | <8000 | 3600~5000 |
Molecular weight distribution | <8000 component〉75% | <8000 component〉60% | <8000 component〉75% |
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2007100614766A CN100467493C (en) | 2007-02-01 | 2007-02-01 | Producing process for low molecular weight calcium heparin |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2007100614766A CN100467493C (en) | 2007-02-01 | 2007-02-01 | Producing process for low molecular weight calcium heparin |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101012289A CN101012289A (en) | 2007-08-08 |
CN100467493C true CN100467493C (en) | 2009-03-11 |
Family
ID=38700029
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2007100614766A Active CN100467493C (en) | 2007-02-01 | 2007-02-01 | Producing process for low molecular weight calcium heparin |
Country Status (1)
Country | Link |
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CN (1) | CN100467493C (en) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102050888B (en) * | 2010-12-13 | 2011-12-07 | 河北常山生化药业股份有限公司 | Method for preparing enoxaparin sodium |
CN102603923B (en) * | 2012-03-02 | 2013-12-11 | 海南灵康制药有限公司 | Heparin calcium compound and preparation method thereof |
CN103382232B (en) * | 2012-05-04 | 2015-11-18 | 常州泰康制药有限公司 | The preparation of nadroparin calcium and purifying process |
CN103012622B (en) * | 2012-12-13 | 2014-08-27 | 南通天龙畜产品有限公司 | Entirely-stirring tank used for heparin sodium extraction process |
CN103275246B (en) * | 2013-06-07 | 2015-08-26 | 山东辰中生物制药有限公司 | A kind of nadroparin calcium production method |
GB2515315A (en) * | 2013-06-19 | 2014-12-24 | Dilafor Ab | New Processes |
CN103408676A (en) * | 2013-07-15 | 2013-11-27 | 河北常山生化药业股份有限公司 | Nadroparin calcium preparation technology |
CN103315951B (en) * | 2013-07-17 | 2014-10-08 | 海南通用同盟药业有限公司 | Low-molecular-weight heparin calcium injection |
CN104072638B (en) * | 2014-07-07 | 2016-08-31 | 兆科药业(合肥)有限公司 | A kind of preparation method of nadroparin calcium |
CN104072639B (en) * | 2014-07-16 | 2015-04-22 | 南京健友生化制药股份有限公司 | Production method for nadroparin calcium |
CN104086673B (en) * | 2014-07-28 | 2016-07-06 | 常州千红生化制药股份有限公司 | A kind of preparation technology of nadroparin calcium |
CN104804110B (en) * | 2015-05-08 | 2017-04-12 | 深圳赛保尔生物药业有限公司 | High-purity nadroparin calcium |
CN108409890A (en) * | 2018-03-16 | 2018-08-17 | 湖北亿诺瑞生物制药有限公司 | A method of producing calciparine from heparin sodium crude |
CN110894246A (en) * | 2019-12-31 | 2020-03-20 | 湖北亿诺瑞生物制药有限公司 | Method for increasing calcium content in low molecular weight heparin calcium |
-
2007
- 2007-02-01 CN CNB2007100614766A patent/CN100467493C/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN101012289A (en) | 2007-08-08 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Hebei Changshan Biochemical Pharmaceutical Co.,Ltd. Assignor: Gao Shuhua Contract fulfillment period: 2009.3.11 to 2027.1.31 Contract record no.: 2009130000032 Denomination of invention: Producing process for low molecular weight calcium heparin Granted publication date: 20090311 License type: Exclusive license Record date: 20090312 |
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LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.3.11 TO 2027.1.31; CHANGE OF CONTRACT Name of requester: HEBEI CHANGSHAN BIOCHEMICAL DRUG INDUSTRY CO., LTD Effective date: 20090312 |
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ASS | Succession or assignment of patent right |
Owner name: HEBEI CHANGSHAN BIOCHEMICAL DRUG INDUSTRY CO., LTD Free format text: FORMER OWNER: GAO SHUHUA Effective date: 20091218 |
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C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20091218 Address after: No 9 prosperous road, Zhengding County, Hebei Patentee after: Hebei Changshan Biochemical Pharmaceutical Co.,Ltd. Address before: Changshan Biochemical Pharmaceutical Co., Ltd., 9 prosperous road, Zhengding County, Hebei Patentee before: Gao Shuhua |
|
C56 | Change in the name or address of the patentee |
Owner name: HEBEI CHANGSHAN BIOCHEMICAL PHARMACEUTICAL CO., LT Free format text: FORMER NAME: HEBEI CHANGSHAN BIOCHEMICAL DRUG INDUSTRY CO., LTD. |
|
CP01 | Change in the name or title of a patent holder |
Address after: No 9 prosperous road, Zhengding County, Hebei Patentee after: HEBEI CHANGSHAN BIOCHEMICAL PHARMACEUTICAL Co.,Ltd. Address before: No 9 prosperous road, Zhengding County, Hebei Patentee before: Hebei Changshan Biochemical Pharmaceutical Co.,Ltd. |
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PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Producing process for low molecular weight calcium heparin Effective date of registration: 20190422 Granted publication date: 20090311 Pledgee: Zhengding Branch of Industrial and Commercial Bank of China Ltd. Pledgor: HEBEI CHANGSHAN BIOCHEMICAL PHARMACEUTICAL Co.,Ltd. Registration number: 2019130000006 |
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CP02 | Change in the address of a patent holder | ||
CP02 | Change in the address of a patent holder |
Address after: 050800 No.71, Menglong street, South District, Zhengding high tech Industrial Development Zone, Zhengding District, China (Hebei) pilot Free Trade Zone, Shijiazhuang City, Hebei Province Patentee after: HEBEI CHANGSHAN BIOCHEMICAL PHARMACEUTICAL Co.,Ltd. Address before: 050800 No. 9, Fuqiang Road, Zhengding County, Hebei Province Patentee before: HEBEI CHANGSHAN BIOCHEMICAL PHARMACEUTICAL Co.,Ltd. |
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PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20220426 Granted publication date: 20090311 Pledgee: Zhengding Branch of Industrial and Commercial Bank of China Ltd. Pledgor: HEBEI CHANGSHAN BIOCHEMICAL PHARMACEUTICAL Co.,Ltd. Registration number: 2019130000006 |
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PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A low molecular weight heparin calcium production process Granted publication date: 20090311 Pledgee: Langfang Bank Co.,Ltd. Shijiazhuang Branch Pledgor: HEBEI CHANGSHAN BIOCHEMICAL PHARMACEUTICAL Co.,Ltd. Registration number: Y2024980013117 |