三种大黄酚制剂在小鼠体内的组织分布研究

Tissue Distribution of Three Chrysophanol Formulations in Mice

目的研究大黄酚聚氰基丙烯酸丁酯纳米囊、大黄酚羟丙基-β-环糊精包合物、大黄酚脂质体在小鼠体内组织分布的差异,通过大黄酚制剂的组织分布特性来了解剂型的药效学特性。以期选出对脑部靶向最强,药效最佳的大黄酚制剂。方法小鼠尾静脉注射同等剂量的制剂,按不同时间点取小鼠的心、肝、脾、肺、肾、脑以及血浆,经过打匀浆去蛋白处理,用高效液相色谱法检测各组织的大黄酚分布。结果三种大黄酚制剂与大黄酚单体溶液相比,均能延长在小鼠体内的消除时间,并且有较好的组织器官靶向性。结论三种大黄酚制剂的组织分布相比较,以大黄酚脂质体在各组织的分布较好,脑组织靶向最为显著。大黄酚脂质体有望成为治疗脑血管疾病临床应用的新剂型。

OBJECTIVE To study the tissue distribution differences of chrysophanol loaded polybutylcyanoacrylate nanocapsules, ehrysophanol-hydroxypropyl-fl-cyclodextrin inclusion eomplex, chrysophanol liposomes in mice, through the tissue distribution of chry sophanol formulations to understand the pharmacodynamic properties of the formulations. With a view to electing for brain targeting the most strong, effect of chrysophanol best fornmlation. METHODS Mice tail intravenous injection of the equivalent dose of 10 mg · kg-1 chrysophanol formulations, by 0. 25, 1, 2, 4, 8, 12 h taking different points of mice heart, liver, spleen, lungs, kidneys, brain and blood plasma, after playing homogenized the protein processing using 1-IPLC for the determination of chrysophanol in organizations of distribution. Chrysophanol was analyzed on a Thermo Hypersil ODS2 chromatographic column with mobile phase methanol-water （90： 10） at 1.0 mL · min-1 flow rate and with column temperature 30℃. The wavelength of UV detector was set at 254 nm and injection volume was 20 μL. RESULTS Three kinds of chrysophanol formulations could prolong the elimination of time in vivo, and better targeting of tissues and organs than chrysophanol N, N-DMF solution. CONCLUSION Three kinds of chrysophanol formulations compared to tissue distribution, chrysophanol liposomes in various tissue distribution better, brain tissue targeting the most significant. Chrysophanol liposomes is expected to become the treatment of cerebrovascular disease clinical application of new dosage forms.