目的 制备二氢杨梅素混合胶束（DMY-MMs），考察口服药动学行为，并计算口服吸收相对生物利用度。方法 通过单因素试验确定主要影响因素的筛选区间，Box-Behnken设计-响应面法优化 DMY-MMs处方。透射电镜观察 DMY-MMs微观形态，X-射线粉末衍射法分析晶型，透析法考察 DMY-MMs 体外释药行为。SD 大鼠分别 ig 给予二氢杨梅素和 DMYMMs，比较药动学行为和吸收相对生物利用度。结果 DMY-MMs最佳处方为：载-药用量比为7.6∶1，Soluplus与TPGS用量比为6.4∶1，水化时间为2 h。包封率、载药量、粒径及Zeta电位分别为（90.21±1.60）%、（10.43±0.21）%、（68.14±7.23）nm 和（1.07±0.26）mV。DMY-MMs外貌为类球形，并以无定型态存在于 DMY-MMs冻干粉中。DMY-MMs体外释药行为符合Weibull模型，释药方程为lnln［1（/ 1－M_t/M_∞）］＝0.639 7lnt－1.781 1（r＝0.978 4）。药动学结果显示，DMY-MMs半衰期（t_1/2）延长至（4.11±1.07）h，C_max增加至4.41倍，相对生物利用度提高至5.18倍。结论 DMY-MMs改变了二氢杨梅素体内药动学行为，显著促进了口服吸收。

Objective To prepare dihydromyricetin mixed micelles (DMY-MMs), and evaluate oral pharmacokinetic behavior and calculate its relative oral bioavailability. Methods Single factor tests were used to determine the screening interval of the main influencing factors, and Box-Behnken design-response surface methodology was employed to optimize prescriptions of DMY-MMs. Transmission electron microscope (TEM) was employed to observe its microscopic appearance. Crystal form of lyophilized powder was analyzed by X-ray powder diffraction (XRPD). Release behavior of DMY-MMs in vitro was investigated by dialysis method. SD rats in each group were administered intragastrically with dihydromyricetin and DMY-MMs, respectively. Pharmacokinetics and relative bioavailability were also compared. Results Optimal formulation of DMY-MMs: carrier to drug ratio was 7.6∶1, Soluplus to TPGS ratio was 6.4∶1, and hydration time was 2 h. Envelopment efficiency, drug loading, particle size and Zeta potential were (90.21 ± 1.60)%, (10.43 ± 0.21)%, (68.14 ± 7.23) nm and (1.07 ± 0.26) mV, respectively. Appearance of DMY-MMs was spherical, dihydromyricetin changed into an amorphous form in DMY-MMs lyophilized powder. Release behavior in vivo of DMY-MMs was in accordance with Higuchi model, and drug release equation was lnln[1/(1－M_t/M_∞)] = 0.639 7lnt－1.781 1 (r = 0.978 4). Pharmacokinetics of DMY-MMs showed that t _1/2 was prolonged to (4.11 ± 1.07) h, C_max was enhanced to 4.41-fold and oral relative bioavailability was increased to 5.18-fold. Conclusion DMY-MMs changed pharmacokinetic behavior of dihydromyricetin in vivo and significantly promoted its oral absorption.

R945

河南省2023年度科技攻关项目（232102310104）；2024年郑州市高等教育教学改革研究与实践项目（2024KCSZ013）