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新型局部安纳米德配方用于缓解外围神经病痛疼痛
Anitha Police1, Vijay Kumar Shankar1, Pankaj Pandey2
1Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
International journal of pharmaceutics
|May 28, 2023
概括
一种新的局部凝将安纳米德与脂肪酸胺酸酶抑制剂西利宾结合在一起,以有效地管理外围神经病痛. 这种方法可以增强安纳米德的作用.
科学领域:
- 药理学和神经科学 药理学和神经科学
- 药物输送系统 药物输送系统
- 疼痛管理 疼痛管理
背景情况:
- 周围神经病变 (PN) 导致严重的疼痛,目前的疗法提供有限的疗效和不良的心理效应 (PSE).
- 安纳米德是一种内源性大麻素,显示了PN的止痛潜力,但由于脂肪酸胺酸酶 (FAAH) 的快速代谢,其生物半衰期很短.
- 对于有效和安全的PN疼痛管理而不是PSE,存在重大未满足的需求.
研究的目的:
- 确定安全的脂肪酸胺基酸酶 (FAAH) 抑制剂,并开发一种局部配方,与安纳米德一起配送,以控制外围神经病变 (PN) 疼痛.
- 在PN的临床前模型中评估局部安纳米德和FAAH抑制剂凝的疗效.
主要方法:
- 用分子对接和体外测试来评估西利马林成分的FAAH抑制潜力.
- 开发了一种局部凝配方,同时提供安纳米德和选定的FAAH抑制剂 (silybin),并针对皮肤透进行了优化.
- 局部配方的疗效在化学疗法诱导的PN的老鼠模型中进行了评估,评估了机械和热性过敏症.
主要成果:
- 分子对接确定了西利宾作为在西利玛林成分中FAAH的强有力的抑制剂.
- 实验室研究证实,西利宾 (20μM) 抑制了>61.8%的FAAH活性,并延长了安纳米德的半衰期.
- 局部凝增强了安纳米德和西利宾的皮肤透,在PN大鼠中显著增加了疼痛值,长达4小时.
结论:
- 随着安纳米德与安全的FAAH抑制剂西利宾的局部联合递送,为有效的外围神经病痛疼痛管理提供了一个有希望的策略.
- 这种方法有可能缓解PN疼痛,同时最大限度地减少与大麻素相关的中枢神经系统副作用.
- 开发的局部凝配方代表了一种可行的治疗选择,以解决未满足的PN疼痛缓解需求.
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