CN101327202B - 注射用维生素k1冻干粉针及制备方法 - Google Patents
注射用维生素k1冻干粉针及制备方法 Download PDFInfo
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- CN101327202B CN101327202B CN2007101265866A CN200710126586A CN101327202B CN 101327202 B CN101327202 B CN 101327202B CN 2007101265866 A CN2007101265866 A CN 2007101265866A CN 200710126586 A CN200710126586 A CN 200710126586A CN 101327202 B CN101327202 B CN 101327202B
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- 239000011772 phylloquinone Substances 0.000 title claims abstract description 71
- 238000002347 injection Methods 0.000 title claims abstract description 47
- 239000007924 injection Substances 0.000 title claims abstract description 47
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 title claims abstract description 44
- MBWXNTAXLNYFJB-NKFFZRIASA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-NKFFZRIASA-N 0.000 title claims abstract description 42
- 235000019175 phylloquinone Nutrition 0.000 title claims abstract description 37
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Abstract
Description
维生素K1(g) | 聚山梨酯-80 (g) | 注射用水 | |
No.1 | 1.0 | 1.0 | 至100ml |
No.2 | 1.0 | 2.0 | 至100ml |
No.3 | 1.0 | 3.0 | 至100ml |
No.4 | 1.0 | 4.0 | 至100ml |
No.5 | 1.0 | 5.0 | 至100ml |
配比 | No.1 | No.2 | No.3 | No.4 | No.5 |
溶解度 | 不澄清 | 不澄清 | 不完全澄清 | 澄清 | 澄清 |
维生素K1 (g) | 聚山梨酯 -80 (g) | 乳糖 (g) | 甘露醇 (g) | 注射用水 | |
No.1 | 1.0 | 4.0 | / | 5.0 | 至100ml |
No.2 | 1.0 | 4.0 | 5.0 | / | 至100ml |
赋形剂 | 溶解能力 | 冻干前溶液稳定性 | 样品外观 |
甘露醇 | 易溶 | 稳定 | 黄色冻干块状物 |
乳糖 | 能溶 | 稳定 | 黄色冻干块状物 |
维生素K1 (g) | 聚山梨酯-80 (g) | 甘露醇(g) | 注射用水 | |
No.1 | 1.0 | 4.0 | 2.0 | 至100ml |
No.2 | 1.0 | 4.0 | 4.0 | 至100ml |
No.3 | 1.0 | 4.0 | 6.0 | 至100ml |
No.4 | 1.0 | 4.0 | 8.0 | 至100ml |
赋形剂浓度 | 样品外观 | 溶解时间(秒) |
2% | 干燥层呈黄色的松散状,形态差 | 45 |
4% | 干燥层呈黄色的较松散状,形态差 | 38 |
6% | 干燥层孔隙适中,形态饱满,疏松的块 状物,外观美观 | 26 |
8% | 干燥层孔隙小,升华阻力大,结构致密. | 32 |
样品编号 | 1 | 2 | 3 |
维生素K1称量(g) | 1.0124 | 1.0098 | 1.0021 |
样品溶液量(ml) | 100 | 100 | 100 |
加入活性炭(%) | 0.2 | 0.1 | - |
搅拌时间(分) | 15 | 15 | - |
过滤次数 | 2 | 2 | 2 |
含量(%) | 98.5 | 99.5 | 99.9 |
细菌内毒素检查 | 符合规定 | 符合规定 | 不符合规定 |
温度(℃) | -50 | -21 | -20 | -19 | -18 | -17 |
电导率值(ΔUS) | 0 | 0.14 | 0.24 | 0.34 | 0.23 | 0.58 |
温度(℃) | -16 | -15 | -14 | -13 | -12 | -11 |
电导率值(ΔUS) | 1.51 | 3.09 | 5.78 | 9.04 | 13.08 | 16.85 |
时间(hr) | 0 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
温度(℃) | 18 | -50 | -50 | -50 | -50 | -16 | -12 | -10 | -8 | -5 | -4 | -3 |
时间(hr) | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 |
温度(℃) | -1 | 0 | 3 | 5 | 6 | 10 | 20 | 30 | 40 | 40 | 40 | 40 |
相对湿度(%) | 31 | 40 | 58 | 66 | 75 | 84 | 92.5 | 95 |
增重率(%) | 0.71 | -0.32 | 1.78 | 1.95 | 5.82 | 9.88 | 26.07 | 39.46 |
时间 (天) | 外观 | 溶液 颜色 | 澄清度 | pH | 干燥 失重 (%) | 标示含 量(%) | 与0天含 量的百分 比(%) |
0 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.49 | 1.14 | 93.41 | 100.0 |
5 | 黄色冻干疏 松块状物 | 深黄色 | 澄清 | 5.55 | 1.17 | 68.26 | 73.1 |
10 | 黄色冻干疏 松块状物 | 深黄色 | 澄清 | 5.57 | 0.98 | 41.32 | 44.2 |
时间 (天) | 外观 | 溶液 颜色 | 澄清度 | pH | 干燥 失重 (%) | 标示含 量(%) | 与0天含 量的百分 比(%) |
0 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.49 | 1.14 | 93.41 | 100.0 |
5 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.53 | 1.01 | 92.77 | 99.3 |
10 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.46 | 0.94 | 92.84 | 99.4 |
时间 (天) | 外观 | 溶液 颜色 | 澄清度 | pH | 干燥 失重 (%) | 标示含 量(%) | 与0天含 量的百分 比(%) |
0 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.49 | 1.14 | 93.41 | 100.0 |
5 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.54 | 1.01 | 91.57 | 98.0 |
10 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.48 | 0.90 | 92.06 | 98.6 |
时间 (天) | 外观 | 溶液 颜色 | 澄清度 | pH | 干燥 失重 (%) | 标示含 量(%) | 与0天含 量的百分 比(%) |
0 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.49 | 1.04 | 93.41 | 100.0 |
5 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.50 | 1.02 | 93.22 | 99.8 |
10 | 黄色冻干疏 松块状物 | 黄色 | 澄清 | 5.54 | 1.12 | 92.18 | 98.7 |
放置时间(min) | 澄清度与颜色 | pH值 | 杂质% |
0 | 澄清黄色 | 5.51 | 0.48 |
30 | 澄清黄色 | 5.52 | 0.47 |
60 | 澄清黄色 | 5.54 | 0.49 |
120 | 澄清黄色 | 5.51 | 0.46 |
240 | 澄清黄色 | 5.52 | 0.48 |
480 | 澄清黄色 | 5.50 | 0.49 |
样品批号 | 040301 | 040302 | 040303 |
外观 | 黄色冻干疏 松块状物 | 黄色冻干疏 松块状物 | 黄色冻干疏 松块状物 |
装量差异 | 符合规定 | 符合规定 | 符合规定 |
澄明度 | 无可见异物 | 无可见异物 | 无可见异物 |
PH值 | 5.71 | 5.68 | 5.75 |
干燥失重% | 1.34% | 1.27% | 1.32% |
澄清度与颜色 | 符合要求 | 符合要求 | 符合要求 |
标示含量% | 105.4% | 101.7% | 104.3% |
无菌 | 符合规定 | 符合规定 | 符合规定 |
细菌内毒素 | 符合规定 | 符合规定 | 符合规定 |
单个杂质 | 总杂质 | |
市售样品1 | 3.0% | 6.0% |
市售样品2 | 2.5% | 4.8% |
市售样品3 | 3.1% | 5.5% |
市售样品4 | 2.6% | 5.3% |
市售样品5 | 1.5% | 3.6% |
发明人研发的粉针 | 0.5% | 1.0% |
单个杂质 | 总杂质 | |
市售样品1 | 5.0% | 8.0% |
市售样品2 | 4.2% | 6.8% |
市售样品3 | 5.7% | 7.5% |
市售样品4 | 4.9% | 7.2% |
市售样品5 | 2.5% | 4.7% |
发明人研发的粉针 | 1.0% | 2.1% |
Claims (6)
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CN101327202B true CN101327202B (zh) | 2011-05-11 |
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CN102657662B (zh) * | 2012-04-18 | 2013-05-08 | 宁辉 | 脂溶性复合维生素ⅱ组合物、冻干粉针剂及其制备方法 |
CN114028334B (zh) * | 2021-12-10 | 2023-08-29 | 卓和药业集团股份有限公司 | 一种肺部给药的免疫抑制剂的制备方法 |
CN117860668A (zh) * | 2023-12-06 | 2024-04-12 | 中润药业有限公司 | 一种维生素k1注射液及其制备方法和应用 |
Citations (2)
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CN1179913A (zh) * | 1996-10-14 | 1998-04-29 | 巴斯福股份公司 | 脂溶性维生素混合物的稳定乳液和干粉及其制备方法和用途 |
CN1596882A (zh) * | 2004-07-22 | 2005-03-23 | 沈阳药科大学 | 维生素k1乳剂及其冻干乳剂及制备方法 |
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CN1179913A (zh) * | 1996-10-14 | 1998-04-29 | 巴斯福股份公司 | 脂溶性维生素混合物的稳定乳液和干粉及其制备方法和用途 |
CN1596882A (zh) * | 2004-07-22 | 2005-03-23 | 沈阳药科大学 | 维生素k1乳剂及其冻干乳剂及制备方法 |
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