开发和系统评估一种低刺激的PFD-AIS配方,用于肺向治疗
Xinze Li1, Chengcheng Li1, Jingxin Sun1
1College of Pharmacy, Yanbian University, Yanji 133002, China.
Pharmaceuticals (Basel, Switzerland)
|February 27, 2026
概括
这项研究开发了一种皮尔芬尼气溶吸入溶液 (PFD-AIS),用于治疗异常性肺纤维化 (IPF). PFD-AIS针对肺部,减少全身暴露和肝脏毒性,同时保持抗纤维菌疗效.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 肺部医学 肺部医学
背景情况:
- 治疗异常性肺纤维化 (IPF) 的口服皮尔芬尼 (PFD) 会引起胃肠道和肝脏的毒性.
- 系统性药物暴露限制了治疗疗效,并增加了不良影响.
研究的目的:
- 开发一种皮尔芬尼气溶吸入溶液 (PFD-AIS),用于向肺部的输送.
- 为了减少PFD的全身暴露和肝毒性.
- 维持或改善PFD的抗纤维菌疗效.
主要方法:
- 已建立的PFD-AIS质量控制分析方法 (内容,相关物质,APSD,递送剂量的统一性).
- 优化的配方和制备过程 (40毫克:4毫升,40°C60分钟,pH4-8).
- 评估了白胺诱导的IPF小鼠模型中的药理动力学和SD大鼠中的药理动力学.
主要成果:
- 对于深层肺沉积,PFD-AIS实现了56.1%的细颗粒分数 (FPF).
- 在小鼠中,肺纤维化病理和肝脏保护 (ALT/AST水平降低) 显著改善.
- 与口服PFD相比,在老鼠中显著减少了系统性暴露 (AUC0-t-63%,AUC0-∞-67%).
结论:
- 开发的PFD-AIS是有效的,可行的,稳定的,质量可控的.
- 肺部导向的PFD的输送提高了治疗疗效.
- PFD-AIS显著降低了全身暴露和肝毒性,为IPF治疗提供了临床优势.
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