CN101474161B - 尼可地尔冻干粉针剂及其制备方法 - Google Patents
尼可地尔冻干粉针剂及其制备方法 Download PDFInfo
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- CN101474161B CN101474161B CN2009100769075A CN200910076907A CN101474161B CN 101474161 B CN101474161 B CN 101474161B CN 2009100769075 A CN2009100769075 A CN 2009100769075A CN 200910076907 A CN200910076907 A CN 200910076907A CN 101474161 B CN101474161 B CN 101474161B
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- nicorandil
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- LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 229960002497 nicorandil Drugs 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 41
- 238000002347 injection Methods 0.000 title claims abstract description 26
- 239000007924 injection Substances 0.000 title claims abstract description 26
- 239000000243 solution Substances 0.000 claims abstract description 66
- 239000003814 drug Substances 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 24
- 238000000859 sublimation Methods 0.000 claims abstract description 21
- 230000008022 sublimation Effects 0.000 claims abstract description 21
- 238000004108 freeze drying Methods 0.000 claims abstract description 19
- 239000000843 powder Substances 0.000 claims abstract description 19
- 230000008569 process Effects 0.000 claims abstract description 7
- 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 claims description 19
- 229930195725 Mannitol Natural products 0.000 claims description 19
- 239000000594 mannitol Substances 0.000 claims description 19
- 235000010355 mannitol Nutrition 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 239000003607 modifier Substances 0.000 claims description 11
- 238000004821 distillation Methods 0.000 claims description 10
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000000470 constituent Substances 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 4
- 229920002307 Dextran Polymers 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000007710 freezing Methods 0.000 claims description 3
- 230000008014 freezing Effects 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- WCTAGTRAWPDFQO-UHFFFAOYSA-K trisodium;hydrogen carbonate;carbonate Chemical compound [Na+].[Na+].[Na+].OC([O-])=O.[O-]C([O-])=O WCTAGTRAWPDFQO-UHFFFAOYSA-K 0.000 claims description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 2
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 2
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 32
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 230000003113 alkalizing effect Effects 0.000 abstract 1
- 230000007812 deficiency Effects 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 32
- 238000005516 engineering process Methods 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000008215 water for injection Substances 0.000 description 17
- 229940079593 drug Drugs 0.000 description 9
- 230000008859 change Effects 0.000 description 6
- 238000009413 insulation Methods 0.000 description 6
- 230000002411 adverse Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 206010008479 Chest Pain Diseases 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical group [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
- 208000007814 Unstable Angina Diseases 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000003890 Coronary Vasospasm Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 201000011634 coronary artery vasospasm Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- CSVGEMRSDNSWRF-UHFFFAOYSA-L disodium;dihydrogen phosphate Chemical compound [Na+].[Na+].OP(O)([O-])=O.OP(O)([O-])=O CSVGEMRSDNSWRF-UHFFFAOYSA-L 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- -1 nitrate compound Chemical class 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims (15)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN2009100769075A CN101474161B (zh) | 2009-01-14 | 2009-01-14 | 尼可地尔冻干粉针剂及其制备方法 |
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CN2009100769075A CN101474161B (zh) | 2009-01-14 | 2009-01-14 | 尼可地尔冻干粉针剂及其制备方法 |
Publications (2)
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CN101474161A CN101474161A (zh) | 2009-07-08 |
CN101474161B true CN101474161B (zh) | 2011-11-16 |
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CN2009100769075A Active CN101474161B (zh) | 2009-01-14 | 2009-01-14 | 尼可地尔冻干粉针剂及其制备方法 |
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Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20140053907A (ko) * | 2011-06-30 | 2014-05-08 | 모찌다 세이야쿠 가부시끼가이샤 | 니코란딜 함유 의약 조성물 |
CN105287404B (zh) * | 2015-10-23 | 2019-02-26 | 北京四环科宝制药有限公司 | 一种稳定性好的尼可地尔冻干制剂的制备方法 |
CN115429763B (zh) * | 2021-06-02 | 2024-01-02 | 北京四环科宝制药股份有限公司 | 尼可地尔片剂及其制备方法 |
CN115624527A (zh) * | 2022-09-20 | 2023-01-20 | 朗天药业(湖北)有限公司 | 一种尼可地尔冻干粉针剂及其制备方法和用途 |
CN115487156A (zh) * | 2022-10-17 | 2022-12-20 | 南京正科医药股份有限公司 | 一种注射用尼可地尔粉针剂及其制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4769381A (en) * | 1986-01-14 | 1988-09-06 | Chugai Seiyaku Kabushiki Kaisha | Nicorandil-containing preparation for injection |
CN1839837A (zh) * | 2006-02-09 | 2006-10-04 | 西安力邦医药科技有限责任公司 | 尼可地尔冻干粉的制备方法 |
-
2009
- 2009-01-14 CN CN2009100769075A patent/CN101474161B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4769381A (en) * | 1986-01-14 | 1988-09-06 | Chugai Seiyaku Kabushiki Kaisha | Nicorandil-containing preparation for injection |
CN1839837A (zh) * | 2006-02-09 | 2006-10-04 | 西安力邦医药科技有限责任公司 | 尼可地尔冻干粉的制备方法 |
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CN101474161A (zh) | 2009-07-08 |
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CB03 | Change of inventor or designer information |
Inventor after: Zhang Jianqiang Inventor after: Zhang Jianxun Inventor after: Cao Xianglin Inventor before: Zhang Jianqiang Inventor before: Zhang Jianxun Inventor before: Cao Xianglin Inventor before: Cai Gang Inventor before: Zhang Yang |
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Free format text: CORRECT: INVENTOR; FROM: ZHANG JIANQIANG ZHANG JIANXUN CAO XIANGLIN CAI GANG ZHANG YANG TO: ZHANG JIANQIANG ZHANG JIANXUN CAO XIANGLIN |
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Address after: 102629 No. 5, Xiangrui street, biomedical base, Daxing District, Beijing Patentee after: Beijing Sihuan Kebao Pharmaceutical Co.,Ltd. Address before: Haiying Lu Zhongguancun Fengtai science and Technology Park of Beijing City, No. 11 Fengtai District 100070 Patentee before: BEIJING SIHUAN KEBAO PHARMACEUTICAL Co.,Ltd. |
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Addressee: Cao Xianglin Document name: Notification of qualified procedures |