目的 制备金丝桃苷磷脂复合物（hyperoside phospholipids complex，Hyp-PC）介孔二氧化硅纳米粒（Hyp-PC mesoporous silica nanoparticles，Hyp-PC-MSN），考察口服药动学行为。方法 以复合率为指标，单因素实验结合Box-Behnken设计-效应面法优化Hyp-PC处方。X射线粉末衍射（X-ray powder diffraction，XRPD）对Hyp-PC进行晶型分析，并测定Hyp-PC的油水分配系数。溶剂挥发法制备Hyp-PC-MSN，扫描电子显微镜观察Hyp-PC-MSN微观形态，并与Hyp-PC比较Hyp-PC-MSN体外溶出情况。SD大鼠分为金丝桃苷组、Hyp-PC组和Hyp-PC-MSN组，测定大鼠血浆中金丝桃苷质量浓度，计算Hyp-PC和Hyp-PC-MSN主要药动学参数及相对口服吸收生物利用度。结果 Hyp-PC最佳处方的复合率接近100%，金丝桃苷在Hyp-PC中以无定型状态存在，油水分配系数明显增大。Hyp-PC-MSN外观形态呈球形，包封率为（93.17±0.85）%，载药量为（7.54±0.33）%，粒径为（163.87±6.15）nm，PDI值为0.108±0.009，ζ电位为（-0.28±0.05）mV。Hyp-PC-MSN明显提高了释药速率和累积释放度。药动学结果显示，Hyp-PC-MSN的达峰时间（t_max）显著性提前，半衰期（t_1/2）延长至（4.56±0.82）h，达峰浓度（C_max）提高至（1 462.62±163.94）ng/mL，相对口服生物利用度提高至3.47倍。结论 Hyp-PC-MSN可提高金丝桃苷体外溶出速率、累积溶出度及口服吸收生物利用度。

Objective To prepare hyperoside phospholipids complex (Hyp-PC) mesoporous silica nanoparticles (Hyp-PC-MSN), and study oral pharmacokinetics behavior. Methods Taking the recombination rate as index, single factor experiment combined with Box-Behnken design-response surface methodology to optimize the formulation of Hyp-PC. Crystalline form of Hyp-PC was analyzed by X-ray powder diffraction (XRPD). Oil-water partition coefficient of Hyp-PC was determined. Solvent evaporation was used to prepare Hyp-PC-MSN. Microscopic appearance of Hyp-PC-MSN was observed by scanning electron microscope (SEM), and its dissolution in vitro was compared to Hyp-PC. SD rats were divided into hyperoside suspension group, Hyp-PC group and Hyp-PC-MSN group, hyperoside concentration in plasma was determined, and main pharmacokinetic parameters and relative oral bioavailability of Hyp-PC and Hyp-PC-MSN were calculated. Results Recombination rate of optimized formulations of Hyp-PC was close to 100%. Hyperoside was an amorphous substance in Hyp-PC and the oil-water partition coefficient was enhanced greatly. Microscopic appearance of Hyp-PC-MSN was spherical in shape. Average envelopment efficiency was (93.17 ±0.85)%, drug loading was (7.54 ±0.33)%, particle size was (163.87 ±6.15) nm, PDI value was 0.108 ±0.009 and ζ potential was (-0.28 ±0.05) mV. Drug release rate and cumulative release rate in vitro was greatly promoted. Pharmacokinetics results showed that t_max of Hyp-PC-MSN was advanced significantly, t_1/2 was prolonged to (4.56 ±0.82) h, C_max was increased to (1 462.62 ±163.94) ng/mL and oral bioavailability was enhanced to 3.47 times. Conclusion Hyp-PC-MSN could increase dissolution rate, cumulative dissolution rate in vitro and the oral bioavailability of hyperoside.

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河南省高等学校重点科研项目计划（23B320013）；妇科肿瘤科研创新团队（2021-TD-02）；河南应用技术职业学院骨干教师（2020-GGJS-Y008）