目的：研究处方及工艺，制备冬凌草甲素长循环冻干脂质体，延长冬凌草甲素体内循环时间。 方法：乙醇注入法制备冬凌草甲素长循环脂质体，冷冻干燥技术制备脂质体冻干制剂。使用葡聚糖凝胶柱纯化脂质体，单因素实验考察不同处方因素对脂质体包封率的影响，研究冻干脂质体复溶后粒径大小、分布及体外释放曲线。大鼠尾静脉给药后，HPLC测定血药浓度，KineticaTM软件计算药动学参数，比较长循环脂质体与普通制剂的药动学特性。 结果：最优长循环脂质体处方为：大豆磷脂∶胆固醇∶DSPE-PEG 2000=1∶0.5∶1.8（w/w），药脂比为1∶6（w/w）。葡萄糖∶甘露醇=3∶1合用作为冻干保护剂，脂质体包封率约65%。复溶后脂质体平均粒径164 nm，分布均匀，长循环脂质体体外释放具缓释效果。大鼠静脉注射冬凌草甲素制剂均符合二室模型，长循环冻干脂质体的MRT约为普通脂质体及溶液组的2倍和6倍；AUC约为普通脂质体及溶液组的2倍及3倍，差异均具统计学意义（P<0.05）。 结论：选用合适的处方及工艺可得到包封率较高的冬凌草甲素长循环脂质体冻干制剂，显著提高冬凌草甲素大鼠体内循环时间和生物利用度。
Objective： To prepare freeze-dried long-circulation oridonin liposomes with optimized parameters. Methods： Ethanol injection method followed by freeze-drying was used to prepare the liposomes.Sephadex column was used to purify liposomes.Effects of formulation factors on entrapment efficiency of long-circulation oridonin liposomes were studied.The particle size，distribution and in vitro release were determined.Pharmacokinetics of oridonin liposomes in rats was determined by HPLC and the pharmacokinetic parameters calculated by KineticaTM software were compared with conventional oridonin liposomes and solution. Results： The optimized lipid formulation for long-circulation liposomes was composed of soy lecithin，cholesterol and DSPE-PEG 2000 with a ratio of 1∶0.5∶1.8(w/w).The ratio of drug to lipid was 1∶6.Freeze-drying protectant was a mixture of glucose and mannitol (3∶1).The entrapment efficiency (EE) of long-circulation oridonin liposomes was about 65%.The particle size of liposomes after hydrolyzation was 164 nm with good DPI.The liposomes showed a sustained drug release in vitro.Intravenous injected oridonin fitted with two-compartment pharmacokinetic model.The MRT of long-circulation liposomes was 2 times and 6 times and AUC was about 2 times and 3 times of conventional liposomes and oridonin solution，respectively. Conclusion： Freeze-dried liposomes with high EE have been obtained by the proposed approach.This long-circulation liposomes extend oridonin half time and significantly increase AUC in rats.
林虎，渠晨曦，俞毅杰，汤逸宁，孙晓译. 冬凌草甲素长循环冻干脂质体的制备及大鼠体内药动学研究[J]. 浙江大学学报（医学版）, 2013, 42(6): 638-643.
LIN Hu，QU Chenxi，YU Yijie，TANG Yining，SUN Xiaoyi. Preparation of freeze-dried long-circulation oridonin liposomes and their pharmacokinetics in rats. Journal of ZheJiang University(Medical Science), 2013, 42(6): 638-643.