水飞蓟宾纳米混悬剂的制备及大鼠体内药动学研究

Studies on Preparation of Silybin Nanosuspension & Its Pharmacokinetics in Rats

目的:探讨静脉注射用水飞蓟宾纳米混悬剂的制备,并评价其大鼠静注给药后的药动学。方法:通过对水飞蓟宾纳米混悬剂理化性质及稳定性的评价,考察水飞蓟宾纳米混悬剂的制备方法、处方工艺,并以溶液剂为参照考察其在大鼠体内的药动学行为。结果:水飞蓟宾纳米混悬剂的平均粒径是(268.90±9.20)nm,多分散性为0.22±0.12。水飞蓟宾溶液剂及纳米混悬剂的药时曲线下面积分别为(34.92±0.98)μg·h·mL-1和(57.12±3.20)μg·h·mL-1,消除半衰期(t1/2)分别为(3.05±0.06)h和(6.14±0.42)h。结论:制备的水飞蓟宾纳米混悬剂理化性质比较稳定,与溶?液剂相比,延长了药物在体内的驻留时间,具有一定的缓释效果。

Objective： To prepare stable silybin nanosuspension for intravenous injection and to study the drug pharmacokinetic behavior in rats. Methods： By a modified solvent diffusion method with high speed dispersion process, silybin nanosuspensions were prepared and then freeze-dried. The characteristics of the silybin nanosuspension were evaluated and the pharmacokinetic behavior of the silybin nanosuspeusion was also investigated compared with the solution following the intravenous injection to rats. Results： The obtained silybin nanosuspension had a size of （268.90 ± 9.20） nm with polydispersity index of 0.22 ± 0.12. The silybin in the uanosuspension became amorphous. Pharmacokinetic behavior of the silybin nanosuspension in rots was investigated compared with the solution. The AUC was increased from （34.92 ± 0.98）μg· h· mL^-1 to （57.12 ± 3.20）μg· h· mL^-1 and the biological half-life（t1/2β） extended from（3.05 ± 0.06） h to （6.14 ± 0.42） h. Conclusion： In Comparison with the SLB-S, the SLB-NS prolongs the residence time in vivo, which shows some slow-release effect.