一种注射用替加环素冻干粉针药学研究及其初步安全性评价

发布时间：2018-04-11 03:07

  本文选题：注射用替加环素 + 冻干工艺　； 参考：《吉林大学》2017年硕士论文

【摘要】：本论文研制的注射用替加环素是基于规避市售品辅料乳糖的应用缺点,以保证药物安全性、稳定性、可控性为目的而开发的一种不含赋形剂的冻干粉针剂。对注射用替加环素的生产处方工艺、质量标准和稳定性进行了系统研究,并对其用药安全进行了初步评价。本论文研究肯定了不含乳糖赋形剂的注射用替加环素临床用药前景,为未来工业化市场化奠定了基础。提供了一种工业化的注射用替加环素冻干粉针处方工艺。在样品溶液中加入0.067%的抗氧化剂,采用依地酸二钠保持样品溶液p H值中性。38 h冷冻干燥阶段无须氮气保护。预冻阶段快速降温至-45℃,维持1 h;退火回温至-20℃,保持2h后再缓慢降温至-45℃,保温2 h;升华干燥分3个阶段逐步由-45℃升温至0℃,用时21.5 h;继续解析干燥至45℃,耗时7 h。对注射用替加环素的性状、鉴别、检查等进行了详细研究,建立了质量标准草案。拟定单个最大杂质不得过2.5%,总杂质不得过3.0%。含量替加环素(C29H39N5O8)应为标示量的90.0%~110.0%。制定的质量标准草案证明样品质量可控。本论文对注射用替加环素进行了影响因素、加速和长期稳定性试验,各指标差异在正常范围内。表明该处方、工艺、贮藏条件下的药品性质稳定。对其家兔血管刺激试验、体外溶血试验、豚鼠主动全身过敏试验及大鼠被动皮肤过敏试验对注射用替加环素的临床给药安全性进行了初步评价。结果显示注射用替加环素对血管无明显刺激性,对红细胞无溶血及凝聚作用,未出现过敏反应。初步判定注射用替加环素临床用药具备安全性。
[Abstract]:The tegacycline for injection is a freeze-dried powder injection without excipient developed in order to avoid the shortcomings of the market excipient lactose and to ensure the safety stability and controllability of the drug.The production process, quality standard and stability of tegacycline for injection were systematically studied, and the safety of tegacycline for injection was preliminarily evaluated.The clinical prospect of tegacyclin for injection without lactose excipient was confirmed in this paper, which laid a foundation for industrialization and marketization in the future.An industrial formulation process of tegacyclin lyophilized powder for injection was provided.0.067% antioxidant was added to the sample solution, and no nitrogen protection was needed during freeze-drying stage of the sample solution with neutral pH value (pH = 38 h) maintained by disodium eurate.In the pre-freezing stage, the temperature dropped rapidly to -45 鈩，

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