关于Bufonis venenum和其脂质体提取物的药理动力学的比较研究
Yun Liu1, Yizhu Luo2, Ming Li2
1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; National Innovation Platform for medical industry-education integration, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
与传统的Bufonis毒液提取物 (BVE) 相比,Bufonis毒液提取物-脂质体 (BVE-LP) 增加了药物暴露,并减少了活性化合物的清除. 这种脂质体配方为改善Bufonis毒液成分的传递提供了一个有前途的治疗选择.
科学领域:
- 药理学和制药学 药理学和制药学
- 药物输送系统 药物输送系统
- 自然产品化学 自然产品化学
背景情况:
- 布福尼斯毒液含有布法迪埃诺利德和基胺,清除速度快,生物可用性低.
- 这些活性成分与显著的不良影响有关.
- 从Bufonis venenum提取物中同时加载脂友和水友化合物存在挑战.
研究的目的:
- 开发和描述Bufonis毒液提取物-脂质体 (BVE-LP) 以改善药物输送.
- 为了比较BVE-LP与传统的Bufonis毒液提取物 (BVE) 的药理学概况.
- 评估BVE-LP在降低毒性和提高治疗疗效方面的潜力.
主要方法:
- 准备和描述Bufonis venenum提取物-脂质体 (BVE-LP) 的方法.
- 开发一种超高性能液态色谱-并联质谱 (UPLC-MS/MS) 试验,用于同时检测12种化学成分.
- 在Sprague-Dawley (SD) 鼠身上进行的药理动力学研究,比较了BVE-LP和BVE组.
主要成果:
- 与BVE.LP相比,BVE.LP显著增加了5西胺的血度-时间曲线 (AUC0-t) 下的面积,比BVE.LP增加了72.36%.
- 暴露 (AUC0-t) 关键的bufadienolides (desacetylcinobufotalin,desacetylcinobufagin,arenobufagin,telocinobufagin) 在BVE-LP组中显著更高.
- 脂质体配方导致几种bufadienolides和indolealkylamines的清除率降低和终端半衰期 (t1/2) 增加.
结论:
- BVE-LP显示了活性Bufonis毒液成分的缓慢的排泄率和增强的全身暴露.
- 脂质体配方有效地解决了与传统Bufonis venenum提取物相关的生物可用性和毒性挑战.
- BVE-LP提出了一种可行的治疗策略,用于有效的治疗和改善Bufonis venenum的临床结果.
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