目的 从苦参中大量制备三叶豆紫檀苷(trifolirhizin,Tri),通过制成磷脂复合物自微乳改善Tri的吸收。方法 采用硅胶柱色谱、重结晶等技术分离制备Tri,综合理化性质和波谱学数据进行结构鉴定。分别采用正交试验、星点设计效应面法优化Tri磷脂复合物(TPC)、TPC自微乳(TPC-SMEDDS)处方。Caco-2模型考察Tri、TPC及TPC-SMEDDS的跨膜转运。结果 磷脂复合物的反应物(即药物Tri)质量浓度为4 mg/mL,Tri与卵磷脂投料物质的量比为1:1.5,反应时间为3 h,复合率可达(93.20±2.01)%。优化的自微乳油相为丙二醇单辛酸酯(Capyrol 90),质量分数占43.65%;乳化剂选择聚氧乙烯蓖麻油(Cremphor EL40),助乳化剂为二乙二醇单乙基醚(Transcutol HP),二者质量比(K_m)为7.58。Caco-2细胞实验表明,Tri的表观渗透系数(P_app)为2.45×10^-7 cm/s;TPC及TPC-SMEDDS的P_app分别为5.13×10^-6 cm/s和1.847×10^-5 cm/s。结论 磷脂复合物及自微乳技术联用可以明显改善Tri的渗透系数,提高Tri跨膜转运效率,提示可提高生物利用度。

Objective To improve the absorption of trifolirhizin (Tri) isolated from Sophora flavescens through preparing it to be phospholipid complex self-microemulsion. Methods In this study, we used the silica gel column chromatography and recrystallization technology to separate and prepare trifolirhizin; And we used physical and chemical properties and spectral data to identificate the structure. We used the orthogonal experiment and the central composite design response surface method (CCD-RSM) to optimize the Tri phospholipid complex (TPC), Tri phospholipid composite material self micro-emulsifying drug delivery system (TPCSMEDDS), and used the Caco-2 model to investigate the transmembrane transport of Tri, TPC, and TPC-SMEDDS, respectively. Results The concentration of the phospholipid complex was 4 mg/mL, the ratio of drug to lecithin was 1:1.5, the reaction time was 3 h, the composite rate was (93.20±2.01)%. The emulsifier was polyoxyethylene castor oil (Cremphor EL40), the auxiliary emulsifier was diethylene glycol ethyl ether (Transcutol HP), and the weight ratio (K_m) of phospholipid complex was 7.58. The experiments of Caco-2 cell showed that the P_app of Tri was 2.45×10^-7 cm/s; The P_app values of TPC and TPC-SMEDDS were 5.13×10^-6 and 1.847×10^-5 cm/s, respectively. Conclusion The permeability coefficient of Tri can be obviously improved by using phospholipid complex and self-microemulsion technique, which also can improve the efficiency of drug delivery.

国家自然科学基金面上项目(81274091);国家教育部春晖计划(Z2008-1-15016);黑龙江省自然科学基金资助项目(D200744);黑龙江中医药大学"优秀创新人才支持计划"项目(2012)