CN102144981B - 一种盐酸吉西他滨冻干粉针剂及其制备方法 - Google Patents
一种盐酸吉西他滨冻干粉针剂及其制备方法 Download PDFInfo
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- CN102144981B CN102144981B CN 201110086103 CN201110086103A CN102144981B CN 102144981 B CN102144981 B CN 102144981B CN 201110086103 CN201110086103 CN 201110086103 CN 201110086103 A CN201110086103 A CN 201110086103A CN 102144981 B CN102144981 B CN 102144981B
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- gemcitabine hydrochloride
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- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 title claims abstract description 94
- 229960005144 gemcitabine hydrochloride Drugs 0.000 title claims abstract description 84
- 238000002347 injection Methods 0.000 title claims abstract description 50
- 239000007924 injection Substances 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 47
- 239000008176 lyophilized powder Substances 0.000 title claims abstract description 37
- 238000004108 freeze drying Methods 0.000 claims abstract description 41
- 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 abstract description 39
- 229930195725 Mannitol Natural products 0.000 claims abstract description 39
- 239000000594 mannitol Substances 0.000 claims abstract description 39
- 235000010355 mannitol Nutrition 0.000 claims abstract description 39
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims abstract description 30
- 239000001632 sodium acetate Substances 0.000 claims abstract description 30
- 235000017281 sodium acetate Nutrition 0.000 claims abstract description 30
- 238000001035 drying Methods 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 19
- 238000009413 insulation Methods 0.000 claims description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- 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 36
- 239000008101 lactose Substances 0.000 claims description 36
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 26
- 239000007788 liquid Substances 0.000 claims description 25
- 239000000843 powder Substances 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 21
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- 239000000203 mixture Substances 0.000 claims description 19
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- 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 16
- 239000013078 crystal Substances 0.000 claims description 14
- 239000008215 water for injection Substances 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 10
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- 238000012360 testing method Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 229940079593 drug Drugs 0.000 description 9
- 229960005277 gemcitabine Drugs 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 238000009472 formulation Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 5
- 230000001954 sterilising effect Effects 0.000 description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 5
- 238000010792 warming Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
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- YMOXEIOKAJSRQX-QPPQHZFASA-N Gemcitabine triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 YMOXEIOKAJSRQX-QPPQHZFASA-N 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000005261 decarburization Methods 0.000 description 2
- 229940020967 gemzar Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010027336 Menstruation delayed Diseases 0.000 description 1
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- 206010060862 Prostate cancer Diseases 0.000 description 1
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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- 229920001971 elastomer Polymers 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
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- 231100000053 low toxicity Toxicity 0.000 description 1
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- 238000011275 oncology therapy Methods 0.000 description 1
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- 239000000546 pharmaceutical excipient Substances 0.000 description 1
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- 239000008213 purified water Substances 0.000 description 1
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- 239000001226 triphosphate Substances 0.000 description 1
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- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
1个月 | 2个月 | 3个月 | 6个月 | |
实验组1 | 99.93% | 99.91% | 99.89% | 99.85% |
实验组2 | 99.90% | 99.87% | 99.85% | 99.81% |
对照组3 | 99.86% | 99.80% | 99.66% | 99.52% |
对照组4 | 99.87% | 99.80% | 99.74% | 99.63% |
对照组5 | 99.92% | 99.92% | 99.90% | 99.75% |
对照组6 | 99.80% | 99.72% | 99.63% | 99.51% |
0个月 | 3个月 | 6个月 | 9个月 | 12个月 | 18个月 | |
实验组1 | 99.96% | 99.94% | 99.91% | 99.89% | 99.85% | 99.83% |
实验组2 | 99.95% | 99.92% | 99.89% | 99.87% | 99.85% | 99.81% |
对照组3 | 99.86% | 99.83% | 99.79% | 99.73% | 99.70% | 99.68% |
对照组4 | 99.84% | 99.80% | 99.72% | 99.69% | 99.66% | 99.56% |
对照组5 | 99.93% | 99.92% | 99.92% | 99.91% | 99.85% | 99.78% |
对照组6 | 99.87% | 99.83% | 99.78% | 99.75% | 99.68% | 99.65% |
实验组1 | 实验组2 | 对照组3 | 对照组4 | 对照组5 | 对照组6 | |
0个月(s) | 3 | 3 | 7 | 9 | 6 | 10 |
6个月(s) | 4 | 6 | 9 | 16 | 8 | 19 |
12个月(s) | 6 | 7 | 12 | 19 | 12 | 21 |
24个月(s) | 11 | 14 | 17 | 32 | 19 | 34 |
实验组1 | 实验组2 | 对照组3 | 对照组4 | 对照组5 | 对照组6 | |
1天 | 无析出 | 无析出 | 无析出 | 无析出 | 无析出 | 无析出 |
3天 | 无析出 | 无析出 | 无析出 | 无析出 | 无析出 | 无析出 |
10天 | 无析出 | 无析出 | 无析出 | 析出微量 | 无析出 | 析出微量 |
30天 | 无析出 | 无析出 | 无析出 | 析出少量 | 无析出 | 析出少量 |
Claims (13)
Priority Applications (1)
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CN 201110086103 CN102144981B (zh) | 2011-04-07 | 2011-04-07 | 一种盐酸吉西他滨冻干粉针剂及其制备方法 |
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CN 201110086103 CN102144981B (zh) | 2011-04-07 | 2011-04-07 | 一种盐酸吉西他滨冻干粉针剂及其制备方法 |
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CN102144981A CN102144981A (zh) | 2011-08-10 |
CN102144981B true CN102144981B (zh) | 2013-02-27 |
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Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102525964B (zh) * | 2012-02-23 | 2013-03-20 | 江苏豪森药业股份有限公司 | 盐酸吉西他滨冻干粉针剂 |
CN102579371A (zh) * | 2012-02-23 | 2012-07-18 | 江苏豪森药业股份有限公司 | 盐酸吉西他滨冻干粉针剂 |
CN102579372B (zh) * | 2012-03-15 | 2013-08-21 | 石药集团中奇制药技术(石家庄)有限公司 | 一种盐酸吉西他滨冻干组合物及其制备方法 |
CN102641248B (zh) * | 2012-04-20 | 2013-05-01 | 湖北一半天制药有限公司 | 注射用盐酸吉西他滨冻干制剂的制备方法 |
CN102614137B (zh) * | 2012-05-02 | 2013-12-11 | 南京臣功制药股份有限公司 | 盐酸吉西他滨冻干粉针剂及其制备方法 |
CN102697740B (zh) * | 2012-06-13 | 2013-07-10 | 南京正大天晴制药有限公司 | 一种注射用盐酸吉西他滨冻干粉及其制备方法 |
CN102764241B (zh) * | 2012-06-19 | 2013-07-03 | 哈药集团生物工程有限公司 | 一种含有盐酸吉西他滨冻干药物组合物 |
CN104000787A (zh) * | 2014-06-03 | 2014-08-27 | 青岛市市立医院 | 一种甘草酸二铵冻干粉针剂及其制备方法 |
CN104042573A (zh) * | 2014-06-03 | 2014-09-17 | 青岛市市立医院 | 一种异甘草酸镁冻干粉针剂及其制备方法 |
CN104825402B (zh) * | 2015-04-23 | 2018-05-18 | 英丽华 | 一种含有吉西他滨的注射用药物组合物 |
CN115590875B (zh) * | 2022-11-08 | 2023-10-27 | 海南锦瑞制药有限公司 | 注射用盐酸吉西他滨的制备方法 |
Citations (5)
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WO2006102533A2 (en) * | 2005-03-23 | 2006-09-28 | Neopharm, Inc. | Pharmaceutically active lipid-based formulation of nucleoside-lipid conjugates |
CN101125126A (zh) * | 2006-08-16 | 2008-02-20 | 丛繁滋 | 一种医用冻干粉(针)剂的制备方法 |
CN101564381A (zh) * | 2009-06-05 | 2009-10-28 | 江苏奥赛康药业有限公司 | 盐酸吉西他滨冻干粉针剂 |
CN101606947A (zh) * | 2009-08-06 | 2009-12-23 | 山东罗欣药业股份有限公司 | 一种盐酸吉西他滨组合物及制备方法 |
CN101926779A (zh) * | 2010-08-19 | 2010-12-29 | 苏州特瑞药业有限公司 | 一种吉西他滨固体脂质纳米粒及其制备方法与用途 |
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2011
- 2011-04-07 CN CN 201110086103 patent/CN102144981B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2006102533A2 (en) * | 2005-03-23 | 2006-09-28 | Neopharm, Inc. | Pharmaceutically active lipid-based formulation of nucleoside-lipid conjugates |
CN101125126A (zh) * | 2006-08-16 | 2008-02-20 | 丛繁滋 | 一种医用冻干粉(针)剂的制备方法 |
CN101564381A (zh) * | 2009-06-05 | 2009-10-28 | 江苏奥赛康药业有限公司 | 盐酸吉西他滨冻干粉针剂 |
CN101606947A (zh) * | 2009-08-06 | 2009-12-23 | 山东罗欣药业股份有限公司 | 一种盐酸吉西他滨组合物及制备方法 |
CN101926779A (zh) * | 2010-08-19 | 2010-12-29 | 苏州特瑞药业有限公司 | 一种吉西他滨固体脂质纳米粒及其制备方法与用途 |
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