芫花酯甲干粉吸入剂的制备及大鼠体内组织分布

Preparation of dry powder inhalation of yuanhuacine and its tissue distribution in rats

将芫花酯甲制成干粉吸入剂直接输送至肺部,实现在肺部的浓集,降低芫花酯甲的毒副作用,达到减毒增效的目的。采用可吸入乳糖作为载体,将芫花酯甲吸附在乳糖表面,以细颗粒分布比例(FPF)为评价指标衡量体外沉积率,筛选出最优处方用于肺部给药,建立大鼠心、肝、脾、肺、肾、脑以及生殖系统的UHPLC-MS/MS分析方法,以静脉注射为参比,考察肺部给药后芫花酯甲在各脏器的分布,计算肺部靶向参数。结果显示,粗糙乳糖与细粉乳糖的比例为10∶1时的干粉吸入剂有最高的FPF,通过比较芫花酯甲肺部给药与静脉注射后在大鼠各组织的分布,发现肺部给药大大提高芫花酯甲在肺组织的浓度,显著减少其在心、肝、脾、肾和生殖系统的分布,表明芫花酯甲干粉吸入剂能使药物在肺部浓集,降低药物在其他组织的分布,提高疗效。

The aim of the present study was to increase distribution of yuanhuacine in the lungs and achieve the purpose of reducing toxicity and increasing efficiency. Therefore, yuanhuacine was designed to be dry powder inhalers innovatively and directly delivered to the lungs. Accordingly, inhaled lactose was used as a carrier to adsorb yuanhuacine on the surface of lactose. Fine particle fraction（FPF）was utilized as evaluation index to filtrate the optimal prescription for pulmonary administration. Besides, an UHPLC-MS/MS method was established for the analysis of heart, liver, spleen, lung, kidney, brain and reproductive system of rats. Intravenous injection was taken as reference to investigate the distribution of yuanhuacine and calculate relevant targeting parameters. The experimental result indicated that the prescription（rough lactose ∶fine lactose=10 ∶1）has the highest FPF, which can be chosen as the most suitable prescription for pulmonary administration of yuanhuacine. Moreover, by comparing the distribution of yuanhuacine through pulmonary administration and intravenous injection, it was found that the concentration of yuanhuacine in the lung tissue was greatly increased by pulmonary administration, which decreased the distribution in heart, liver, spleen, kidney, brain and reproductive system, thus sequentially reducing the toxicity in other tissues and increased the efficiency.