CN102558393A - 一种达肝素钠制备工艺 - Google Patents
一种达肝素钠制备工艺 Download PDFInfo
- Publication number
- CN102558393A CN102558393A CN2011104579823A CN201110457982A CN102558393A CN 102558393 A CN102558393 A CN 102558393A CN 2011104579823 A CN2011104579823 A CN 2011104579823A CN 201110457982 A CN201110457982 A CN 201110457982A CN 102558393 A CN102558393 A CN 102558393A
- Authority
- CN
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- Prior art keywords
- sodium
- heparin
- dalteparin sodium
- dalteparin
- preparation
- 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.)
- Granted
Links
- 229940018872 dalteparin sodium Drugs 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 229920000669 heparin Polymers 0.000 claims abstract description 23
- 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 abstract description 17
- 229960001008 heparin sodium Drugs 0.000 claims abstract description 17
- 238000004108 freeze drying Methods 0.000 claims abstract description 8
- 230000001105 regulatory effect Effects 0.000 claims abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 239000007788 liquid Substances 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000003055 low molecular weight heparin Substances 0.000 claims description 10
- 239000002244 precipitate Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 235000010288 sodium nitrite Nutrition 0.000 claims description 8
- 238000005516 engineering process Methods 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 238000000108 ultra-filtration Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 150000002978 peroxides Chemical class 0.000 claims description 5
- 239000008213 purified water Substances 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 230000008021 deposition Effects 0.000 claims description 3
- 238000001556 precipitation Methods 0.000 claims description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 3
- 239000012279 sodium borohydride Substances 0.000 claims description 3
- 238000011146 sterile filtration Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 17
- 239000000047 product Substances 0.000 abstract description 17
- 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 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 5
- 210000004369 blood Anatomy 0.000 abstract description 5
- 229960002897 heparin Drugs 0.000 abstract description 5
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 208000006011 Stroke Diseases 0.000 abstract description 3
- 230000001858 anti-Xa Effects 0.000 abstract description 3
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- 239000003146 anticoagulant agent Substances 0.000 abstract description 3
- 208000029078 coronary artery disease Diseases 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 208000004043 venous thromboembolism Diseases 0.000 abstract description 3
- 206010014522 Embolism venous Diseases 0.000 abstract description 2
- 230000002785 anti-thrombosis Effects 0.000 abstract description 2
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- 239000012043 crude product Substances 0.000 abstract 1
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- 239000000243 solution Substances 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 101100136092 Drosophila melanogaster peng gene Proteins 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
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- 208000007536 Thrombosis Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 210000001557 animal structure Anatomy 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
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- 230000023555 blood coagulation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
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- 230000018044 dehydration Effects 0.000 description 1
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- 238000006073 displacement reaction Methods 0.000 description 1
- 238000005008 domestic process Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000011027 product recovery Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Images
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
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CN 201110457982 CN102558393B (zh) | 2011-12-31 | 2011-12-31 | 一种达肝素钠制备工艺 |
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Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103214596A (zh) * | 2013-05-14 | 2013-07-24 | 枣庄赛诺康生化股份有限公司 | 由肝素钠粗品直接生产低分子量肝素钠的方法 |
CN103408676A (zh) * | 2013-07-15 | 2013-11-27 | 河北常山生化药业股份有限公司 | 一种那屈肝素钙制备工艺 |
CN104045744A (zh) * | 2014-06-26 | 2014-09-17 | 常州千红生化制药股份有限公司 | 达肝素钠的制备方法 |
CN104045743A (zh) * | 2014-06-26 | 2014-09-17 | 常州千红生化制药股份有限公司 | 一种精品达肝素钠的制备方法 |
CN104072635A (zh) * | 2014-03-07 | 2014-10-01 | 常山生化药业(江苏)有限公司 | 一种用阴离子交换树脂纯化制备达肝素钠的方法 |
CN104098716A (zh) * | 2014-07-16 | 2014-10-15 | 南京健友生化制药股份有限公司 | 一种达肝素钠精品的生产方法 |
CN104262508A (zh) * | 2014-09-19 | 2015-01-07 | 东营天东制药有限公司 | 一种汀肝素钠制备工艺 |
CN104262510A (zh) * | 2014-10-11 | 2015-01-07 | 枣庄赛诺康生化股份有限公司 | 一种超低游离硫酸基的低分子量肝素钠的制备方法 |
CN105294885A (zh) * | 2015-11-23 | 2016-02-03 | 山东大学 | 一种新来源亚硝酸降解低分子肝素的制备方法 |
CN105884934A (zh) * | 2014-10-17 | 2016-08-24 | 北京海吉星医疗科技有限公司 | 一种达肝素钠的制备方法 |
CN107141373A (zh) * | 2017-07-01 | 2017-09-08 | 湖北亿诺瑞生物制药有限公司 | 一种新的达肝素钠的制备工艺 |
CN107236057A (zh) * | 2017-05-19 | 2017-10-10 | 南京健友生化制药股份有限公司 | 一种获得达肝素钠的降解方法 |
WO2019159092A1 (en) | 2018-02-14 | 2019-08-22 | Biological E Limited | Improved process for the preparation of dalteparin sodium |
CN113024689A (zh) * | 2021-05-21 | 2021-06-25 | 江西浩然生物制药有限公司 | 一种达肝素钠分子量的控制方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1421464A (zh) * | 2002-11-29 | 2003-06-04 | 上海惠海生化制品厂 | 低分子肝素钠(钙)及其制备方法 |
CN1749284A (zh) * | 2005-09-19 | 2006-03-22 | 南京健友生物化学制药有限公司 | 低分子肝素纯化方法 |
CN1847268A (zh) * | 2005-04-11 | 2006-10-18 | 丘比株式会社 | 低分子肝素或者其盐、含有其的医药组合物及其制造方法 |
-
2011
- 2011-12-31 CN CN 201110457982 patent/CN102558393B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1421464A (zh) * | 2002-11-29 | 2003-06-04 | 上海惠海生化制品厂 | 低分子肝素钠(钙)及其制备方法 |
CN1847268A (zh) * | 2005-04-11 | 2006-10-18 | 丘比株式会社 | 低分子肝素或者其盐、含有其的医药组合物及其制造方法 |
CN1749284A (zh) * | 2005-09-19 | 2006-03-22 | 南京健友生物化学制药有限公司 | 低分子肝素纯化方法 |
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103214596A (zh) * | 2013-05-14 | 2013-07-24 | 枣庄赛诺康生化股份有限公司 | 由肝素钠粗品直接生产低分子量肝素钠的方法 |
CN103408676A (zh) * | 2013-07-15 | 2013-11-27 | 河北常山生化药业股份有限公司 | 一种那屈肝素钙制备工艺 |
CN104072635B (zh) * | 2014-03-07 | 2016-09-28 | 常山生化药业(江苏)有限公司 | 一种用阴离子交换树脂纯化制备达肝素钠的方法 |
CN104072635A (zh) * | 2014-03-07 | 2014-10-01 | 常山生化药业(江苏)有限公司 | 一种用阴离子交换树脂纯化制备达肝素钠的方法 |
CN104045743A (zh) * | 2014-06-26 | 2014-09-17 | 常州千红生化制药股份有限公司 | 一种精品达肝素钠的制备方法 |
CN104045744A (zh) * | 2014-06-26 | 2014-09-17 | 常州千红生化制药股份有限公司 | 达肝素钠的制备方法 |
CN104098716A (zh) * | 2014-07-16 | 2014-10-15 | 南京健友生化制药股份有限公司 | 一种达肝素钠精品的生产方法 |
CN104098716B (zh) * | 2014-07-16 | 2015-04-22 | 南京健友生化制药股份有限公司 | 一种达肝素钠精品的生产方法 |
CN104262508A (zh) * | 2014-09-19 | 2015-01-07 | 东营天东制药有限公司 | 一种汀肝素钠制备工艺 |
CN104262510A (zh) * | 2014-10-11 | 2015-01-07 | 枣庄赛诺康生化股份有限公司 | 一种超低游离硫酸基的低分子量肝素钠的制备方法 |
CN104262510B (zh) * | 2014-10-11 | 2016-08-17 | 山东万邦赛诺康生化制药股份有限公司 | 一种超低游离硫酸基的低分子量肝素钠的制备方法 |
CN105884934A (zh) * | 2014-10-17 | 2016-08-24 | 北京海吉星医疗科技有限公司 | 一种达肝素钠的制备方法 |
CN105294885A (zh) * | 2015-11-23 | 2016-02-03 | 山东大学 | 一种新来源亚硝酸降解低分子肝素的制备方法 |
CN107236057A (zh) * | 2017-05-19 | 2017-10-10 | 南京健友生化制药股份有限公司 | 一种获得达肝素钠的降解方法 |
CN107141373A (zh) * | 2017-07-01 | 2017-09-08 | 湖北亿诺瑞生物制药有限公司 | 一种新的达肝素钠的制备工艺 |
WO2019159092A1 (en) | 2018-02-14 | 2019-08-22 | Biological E Limited | Improved process for the preparation of dalteparin sodium |
JP2021513593A (ja) * | 2018-02-14 | 2021-05-27 | バイオロジカル イー リミテッド | ダルテパリンナトリウムを調製する改善された方法 |
US11492421B2 (en) | 2018-02-14 | 2022-11-08 | Biological E Limited | Process for the preparation of Dalteparin sodium |
CN113024689A (zh) * | 2021-05-21 | 2021-06-25 | 江西浩然生物制药有限公司 | 一种达肝素钠分子量的控制方法 |
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