CN112843003A - 一种注射用拉氧头孢钠的冻干粉及其冻干工艺 - Google Patents
一种注射用拉氧头孢钠的冻干粉及其冻干工艺 Download PDFInfo
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Abstract
本发明提供一种注射用拉氧头孢钠的冻干粉及其冻干工艺，其中冻干粉包括以下重量份原料：拉氧头孢钠20～40份、冻干辅剂8～15份、赋形剂6～18份、水30～55份，通过对原料工艺的优化，制备冻干辅剂、两次干燥，使得原料质量稳定、杂质少、纯度高、不良反应少、药效高；同时对制剂配液工艺进行创新改进，降低配液温度，保证药液质量稳定；同时对冻干工艺采用二次干燥，使得成品水分、杂质和质量更稳定。
Description
技术领域
本发明涉及药品制备领域，特别涉及一种注射用拉氧头孢钠的冻干粉及其冻干工艺。
背景技术
注射用拉氧头孢钠，适应症为用于敏感菌引起的各种感染症，如败血症、脑膜炎、呼吸系统感染症(肺炎、支气管炎、支气管扩张症、肺化脓症、脓胸等)，消化系统感染症(胆道炎、胆囊炎等)，腹腔内感染症(肝脓疡、腹膜炎等)，泌尿系统及生殖系统感染症(肾孟肾炎、膀胱炎、尿道炎、淋病、副睾炎、子宫内感染、子宫附件炎、盆腔炎等)，皮肤及软组织感染、骨、关节感染及创伤感染。
目前，注射用拉氧头孢钠冻干粉剂由于生产时所用辅料为单一的甘露醇，它存在生产时冻干时间长，干燥温度高，能耗大，成品澄清度和溶液颜色合格率低，冻干工艺得到的注射用拉氧头孢钠水分、杂质高，质量不稳定。
发明内容
鉴于此，本发明提出一种注射用拉氧头孢钠的冻干粉及其冻干工艺，解决上述问题。
本发明的技术方案是这样实现的：一种注射用拉氧头孢钠的冻干粉：包括以下重量份原料：拉氧头孢钠20～40份、冻干辅剂8～15份、赋形剂6～18份、水30～55份，所述冻干辅剂由银杏内酯、β-葡萄糖苷酶、甘露醇组成，所述赋形剂选自乳糖、甘露醇、右旋糖苷、甘氨酸、葡萄糖中的一种或多种，
所述注射用拉氧头孢钠的冻干粉的冻干方法，包括以下步骤：
S1、制备冻干辅剂：将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合，加入3～5倍体积水搅拌，搅拌速率为600～1200rpm，搅拌时间60～150s，再置于-14～10℃下放置，得到冻干辅剂；
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合，用振荡器混匀，制成悬液，
S3、一次干燥：将悬液置于搁板，缓慢升至-6～-3℃，保温，待一次干燥中的制品的冰晶完全消失后，继续保温3～5小时；
S4、二次干燥：将S3干燥后的悬液升温至12～15℃，保温0.3～1.5小时，搁板继续升温至33～37℃，待二次干燥中的制品的温度达33～37℃后，继续保温3～5小时。
进一步的，一种注射用拉氧头孢钠的冻干粉，包括以下重量份原料：拉氧头孢钠30份、冻干辅剂12份、赋形剂12份、水43份，所述冻干辅剂由重量份比为1～3:0.1～2:0.6～3.9的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
进一步的，所述S1中放置时间为3～8h。
进一步的，所述S3中升温速率为0.30～0.35℃/min。
进一步的，所述S4中升温速率为0.50～0.55℃/min。
进一步的，所述S4中继续升温速率为0.30～0.35℃/min。
与现有技术相比，本发明的有益效果是：
本发明经合理选择原料，科学配比，冻干辅剂中选择杏内酯、β-葡萄糖苷酶、甘露醇按比例混合，辅助冻干，避免干燥过程发生水解以及发生氧化、凝聚、融合等现象，通过对原料工艺的优化，使得原料质量稳定、杂质少、纯度高、不良反应少、药效高；同时对制剂配液工艺进行创新改进，降低配液温度，保证药液质量稳定；同时对冻干工艺采用二次干燥，使得成品水分、杂质和质量更稳定。
具体实施方式
为了更好理解本发明技术内容，下面提供具体实施例，对本发明做进一步的说明。
本发明实施例所用的实验方法如无特殊说明，均为常规方法。
本发明实施例所用的材料、试剂等，如无特殊说明，均可从商业途径得到。
实施例1
一种注射用拉氧头孢钠的冻干粉，包括以下重量份原料：拉氧头孢钠20份、冻干辅剂8份、乳糖6份、水30份，所述冻干辅剂由重量份比为1:0.1:0.6的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
实施例2
一种注射用拉氧头孢钠的冻干粉，包括以下重量份原料：拉氧头孢钠40份、冻干辅剂15份、甘露醇18份、水55份，所述冻干辅剂由重量份比为3:2:3.9的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
实施例3
一种注射用拉氧头孢钠的冻干粉，包括以下重量份原料：拉氧头孢钠30份、冻干辅剂12份、甘氨酸12份、水42份，所述冻干辅剂由重量份比为2:1.2:2.3的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
上述实施例1～3按照以下冻干工艺：
S1、制备冻干辅剂：将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合，加入3～5倍体积水搅拌，搅拌速率为900rpm，搅拌时间120s，再置于-12℃下放置5h，得到冻干辅剂；
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合，用振荡器混匀，制成悬液，
S3、一次干燥：将悬液置于搁板，温度以0.33℃/min的速度缓慢升至-4℃，保温，待一次干燥中的制品的冰晶完全消失后，继续保温4小时；
S4、二次干燥：将S3干燥后的悬液再以温度以0.53℃/min的速度升至13℃，保温1小时，搁板继续以0.33℃/min的速度升至35℃，待二次干燥中的制品的温度达34℃后，继续保温4小时。
实施例4
本实施例与实施例3的区别在于，一种注射用拉氧头孢钠的冻干粉的冻干工艺，包括以下步骤：
S1、制备冻干辅剂：将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合，加入3～5倍体积水搅拌，搅拌速率为600rpm，搅拌时间60s，再置于-14℃下放置，得到冻干辅剂；
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合，用振荡器混匀，制成悬液，
S3、一次干燥：将悬液置于搁板，按0.30℃/min的速率缓慢升至-6℃，保温，待一次干燥中的制品的冰晶完全消失后，继续保温3小时；
S4、二次干燥：将S3干燥后的悬液按0.50℃/min的速率升温至12℃，保温0.3小时，搁板按0.30℃/min的速率继续升温至33℃，待二次干燥中的制品的温度达33℃后，继续保温3小时。
实施例5
本实施例与实施例3的区别在于，一种注射用拉氧头孢钠的冻干粉的冻干工艺，包括以下步骤：
S1、制备冻干辅剂：将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合，加入3～5倍体积水搅拌，搅拌速率为1200rpm，搅拌时间150s，再置于-10℃下放置，得到冻干辅剂；
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合，用振荡器混匀，制成悬液，
S3、一次干燥：将悬液置于搁板，按0.35℃/min的速率缓慢升至-3℃，保温，待一次干燥中的制品的冰晶完全消失后，继续保温5小时；
S4、二次干燥：将S3干燥后的悬液按0.55℃/min的速率升温至15℃，保温1.5小时，搁板按0.35℃/min的速率继续升温至37℃，待二次干燥中的制品的温度达37℃后，继续保温5小时。
实施例6
本实施例与实施例3的区别在于，一种注射用拉氧头孢钠的冻干粉的冻干工艺，所述S3中升温速率为0.38℃/min。
对比例1
本对比例和实施例3的区别在于，一种注射用拉氧头孢钠的冻干粉，包括以下重量份原料：拉氧头孢钠50份、冻干辅剂20份、赋形剂20份、水25份。
对比例2
本对比例和实施例3的区别在于，一种注射用拉氧头孢钠的冻干粉，所述冻干辅剂由重量份比为4:3:4的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
对比例3
本对比例和实施例3的区别在于，一种注射用拉氧头孢钠的冻干粉，所述冻干辅剂由等量的右旋糖酐、β-葡萄糖苷酶、甘露醇组成。
一、稳定性
参照《中国药典》的要求，对实施例1～6和对比例1～3所制得样品的性状、pH值、含量、总杂。
由上表可知，本方法制备的注射用冻干粉针剂，呈类白色疏松块状物，pH值呈中性，含量高，总杂少，由于其他上市产品，产品质量稳定，且质量更优。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (6)
1.一种注射用拉氧头孢钠的冻干粉，其特征在于：包括以下重量份原料：拉氧头孢钠20～40份、冻干辅剂8～15份、赋形剂6～18份、水30～55份，所述冻干辅剂由银杏内酯、β-葡萄糖苷酶、甘露醇组成，所述赋形剂选自乳糖、甘露醇、右旋糖苷、甘氨酸、葡萄糖中的一种或多种；
所述的注射用拉氧头孢钠的冻干粉的冻干方法，包括以下步骤：
S1、制备冻干辅剂：将杏内酯、β-葡萄糖苷酶、甘露醇按比例混合，加入3～5倍体积水搅拌，搅拌速率为600～1200rpm，搅拌时间60～150s，再置于-14～-10℃下放置，得到冻干辅剂；
S2、按上述重量份将拉氧头孢钠、冻干辅剂、赋形剂、水混合，用振荡器混匀，制成悬液，
S3、一次干燥：将悬液置于搁板，缓慢升至-6～-3℃，保温，待一次干燥中的制品的冰晶完全消失后，继续保温3～5小时；
S4、二次干燥：将S3干燥后的悬液升温至12～15℃，保温0.3～1.5小时，搁板继续升温至33～37℃，待二次干燥中的制品的温度达33～37℃后，继续保温3～5小时。
2.如权利要求1所述的一种注射用拉氧头孢钠的冻干粉，其特征在于：包括以下重量份原料：拉氧头孢钠30份、冻干辅剂12份、赋形剂12份、水43份，所述冻干辅剂由重量份比为1～3:0.1～2:0.6～3.9的银杏内酯、β-葡萄糖苷酶、甘露醇组成。
3.如权利要求1所述的一种注射用拉氧头孢钠的冻干粉，其特征在于：所述冻干方法S1中放置时间为3～8h。
4.如权利要求1所述的一种注射用拉氧头孢钠的冻干粉，其特征在于：所述冻干方法S3中升温速率为0.30～0.35℃/min。
5.如权利要求1所述的一种注射用拉氧头孢钠的冻干粉，其特征在于：所述S4中升温速率为0.50～0.55℃/min。
6.如权利要求3所述的一种注射用拉氧头孢钠的冻干粉，其特征在于：所述冻干方法S4中继续升温速率为0.30～0.35℃/min。
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| CN115737573A (zh) * | 2022-11-30 | 2023-03-07 | 杭州沐源生物医药科技有限公司 | 一种注射用拉氧头孢钠冻干粉剂及其制备方法 |
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| CN114557952A (zh) * | 2022-02-22 | 2022-05-31 | 张文博 | 一种脐带间充质干细胞因子冻干粉的制备方法 |
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