目的 制备芒柄花素-2-羟丙基-β-环糊精（FMN-2-HP-β-CD）包合物，并对其包合行为进行初步探讨。方法 通过对比研磨法、酸碱中和搅拌法和超声法，筛选FMN-2-HP-β-CD包合物制备方法；以HPLC法测定芒柄花素（FMN）的量；以载药量为指标，以正交试验设计法优化FMN-2-HP-β-CD包合物的制备处方及工艺；采用扫描电子显微镜（SEM）、X射线衍射分析（XRD）验证包合物的形成；通过相溶解度法考察包合物中主客体分子之间的包合物物质的量之比，并通过分子对接法与相关热力学参数的计算对其包合行为进行探讨。结果 选用酸碱中和搅拌法，在FMN与2-羟丙基-β-环糊精（2-HP-β-CD）物质的量之比为1∶1、温度50 ℃、2-HP-β-CD质量浓度为5 g/L的条件下制备FMN-2-HP-β-CD包合物，经验证其载药量达（9.42±0.25）%；相溶解度曲线呈A_L型，包合稳定常数随着温度升高而减小；热力学参数显示，FMN与2-HP-β-CD包合是一个以焓变作为主要驱动力的放热、熵减小的过程；分子模拟表明FMN是以7-OH部分从2-HP-β-CD的大口端进入内腔，与2-HP-β-CD上的氧原子形成1个氢键。结论 制备的FMN-2-HP-β-CD包合物重复性好，能提高FMN的溶解度；分子模拟FMN与2-HP-β-CD包合行为与相关热力学参数结果相符合。

Objective To prepare formononetin-2-hydroxypropyl-β-cyclodextrin (FMN-2-HP-β-CD) inclusion complex and to explore its inclusion behavior. Methods The preparation method of FMN-2-HP-β-CD inclusion complex was optimized by comparing kneading method, stirring method, and ultrasonic method. The content of FMN was assayed by HPLC. The preparation technology of FMN-2-HP-β-CD inclusion complex was optimized by orthogonal design taking drug loading capacity as index. The inclusion complex was characterized by scanning electronic microscopy (SEM) and X-ray diffractometry (XRD). Phase solubility method was used to calculate the molar ratio between host and guest molecules and the related thermodynamic parameter. The molecular simulation was processed to investigate the inclusion behavior of FMN and 2-HP-β-CD. Results Using acid-base neutralization agitation method, the optimum inclusion conditions were: the molar ratio of FMN with 2-HP-β-CD 1:1, inclusion temperature 50 ℃, and 2-HP-β-CD concentration 5 g/L. The drug loading capacity was (9.42 ± 0.25)%. The phase solubility curve was A_L type and the stability constants decrease with the increasing temperature. The thermodynamic parameters showed that the inclusion of FMN and 2-HP-β-CD is a process of exothermic and entropy decreasing with enthalpy change as the main driving force. Molecular simulation showed that the 7-OH of the FMN takes the lead from the wider rim of 2-HP-β-CD into the cavity, and forms a hydrogen bond with the oxygen atom on the 2-HP-β-CD. Conclusion The FMN-2-HP-β-CD inclusion complex prepared by the optimum process conditions has good repeatability, which can improve the solubility of FMN. Molecular simulation of FMN and 2-HP-β-CD inclusion behavior was consistent with the relevant thermodynamic parameters.

国家自然科学基金项目（81403111）