制备和评估长效注射式利沃提里津产药配方的制备和评估
1Department of Biopharmaceutical Engineering, College of Life Science and Nano Technology, Hannam University, Deajeon 34054, Republic of Korea.
研究人员开发了长期起作用的注射式利沃提里津 (LCZ) 前药,达到持续治疗性血水平超过30天. 这项创新增强了抗组胺剂的输送,可能改善患者的坚持.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 药用化学 医学化学
背景情况:
- 利沃提里津 (LCZ) 是第二代抗胰岛素,其半衰期很短,需要频繁服用.
- 缺乏坚持,特别是在儿科患者群体中,可能是每日剂量方案的结果.
- 长效配方的开发对于改善治疗结果至关重要.
研究的目的:
- 为了合成和表征长效注射配方的脂友性levosetirizine (LCZ) 前药物.
- 评估新型LCZ前药物的物理化学稳定性,酶化水解和体内药理动力学.
- 评估持续药物释放和改善坚持的潜力.
主要方法:
- 通过化合成莱沃提里二甲酸盐 (LCZ-D) 和劳拉酸盐 (LCZ-L).
- 使用NMR,FT-IR和DSC进行表征;在以石油为基础的车辆中配制.
- 用猪肝酶 (PLE) 和老鼠血进行体外水解研究;在老鼠体内药理动力学评估.
- 在各种温度条件下的稳定性测试和抗氧化作用的评估.
主要成果:
- LCZ-D和LCZ-L表现出一级水解动力学,水解速率取决于酶度和生物液.
- 在老鼠中进行的药理动力学研究表明,药物释放持续,配方可维持治疗性血度超过30天.
- 辅助剂的选择影响了全身暴露;BHT的含有改善了高温下氧化稳定性.
结论:
- 开发的LCZ前药物配方显示出长效注射药物输送的巨大潜力.
- 实现了超过30天的持续治疗性血水平,解决了短期LCZ的局限性.
- 辅助剂调节提供了一种可行的策略来控制药物释放动力学和全身暴露,以提高治疗疗效.
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