目的 制备二氢杨梅素（DMY）磷脂复合物（DMY-PC）和二氢杨梅素磷脂复合物纳米结构脂质载体（DMY-PC-NLC），并分别进行体内外评价。方法 溶剂挥发法制备DMY-PC，高压均质法制备DMY-PC-NLC。采用正交试验优化DMY-PC-NLC处方中固液脂质比例，固液脂质材料总用量，DMY-PC投药量和泊洛沙姆188用量，得出DMY-PC-NLC最佳制备处方。5%甘露醇为冻干保护剂进一步将DMY-PC-NLC制备成冻干粉末，并比较DMY-PC和DMY-PC-NLC体外释放和体内药动学行为。结果 DMY在DMY-PC中以无定形状态存在，¹H-NMR显示DMY化学结构未发生改变。正交试验确定DMY-PC-NLC的最佳处方为固液脂质比例为5：1，固液脂质材料总用量为325 mg，DMY-PC投药量为45 mg，泊洛沙姆188用量为0.9%。DMY-PC-NLC平均粒径为（197.25±4.42）nm，Zeta电位为（-18.2±2.1）mV，包封率为（71.68±1.36）%，载药量为 （3.94±0.24）%。DMY-PC-NLC体外释药模型符合Weibull模型，方程为lnln（1-M_t/M_∞）=0.700 1 lnt-1.954 1（r=0.971 4）。与DMY原料药相比，DMY-PC相对生物利用度提高至1.63倍，而DMY-PC-NLC提高至3.22倍。结论 与DMY-PC相比，DMY-PC-NLC进一步促进了DMY的体内吸收，有效提高了DMY口服吸收生物利用度。

Objective To prepare dihydromyricetin (DMY) phospholipids complex (DMY-PC) and its nanostructured lipid carriers (DMY-PC-NLC), and carry out in vitro and in vivo evaluation. Methods DMY-PC was prepared by solvent evaporation method. High pressure homogenization method was used to prepare DMY-PC-NLC. Orthogonal test was employed to optimize the ratio of solid/liquid lipid, dose of lipids materials, dose of DMY-PC and the concentration of emulsifier of poloxamer. The lyophilized powder of DMY-PC-NLC was prepared with 5% of mannitol as protective agent. The comparation of in vitro release and pharmacokinetics between DMY-PC and DMY-PC-NLC was also studied. Results DMY was in an amorphous state in DMY-PC. The results of ¹HNMR showed that the structure of DMY was not changed. The optimized prescription of DMY-PC-NLC determined by orthogonal test was as follow:The ratio of solid/liquid lipid was 5:1, dose of lipids materials was 325 mg, dose of DMY-PC was 45 mg and the concentration of emulsifier of poloxamer was 0.9%. The average size, Zeta potential, entrapment efficiency and drug loading of DMY-PC-NLC was (197.25 ±4.42) nm, (−18.2 ±2.1) mV, (71.68 ±1.36)% and (3.94 ±0.24)%, respectively. The in vitro release model was accord with Weibull model and the equation was lnln(1-M_t/M_∞)=0.700 1 lnt-1.954 1 (r=0.971 4). The relative bioavailability of DMY-PC and DMY-PC-NLC were enhanced to 1.63 and 3.22 times compared to DMY, respectively. Conclusion Compared with DMY-PC, the absorption was promoted by DMY-PC-NLC in further, and the bioavailability of DMY was enhanced effectively.

国家自然科学基金资助项目（81771025）；河南省重大科技专项（162102310003）