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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AL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 inclusion complex of formicin-2-hydroxypropyl-β-cyclodextrin (FMN-2-HP-β-CD) and to investigate its inclusion behavior. Methods The preparation method of FMN-2-HP-β-CD inclusion complex was screened by comparative grinding method, acid-base neutralization stirring method and ultrasonic method. The amount of forminonetin (FMN) As the index, the orthogonal test design was used to optimize the preparation and preparation of FMN-2-HP-β-CD inclusion complex. The formation of inclusion complex was confirmed by scanning electron microscopy (SEM) and X-ray diffraction analysis Through the phase solubility method, the content ratio of inclusion compound between host-guest molecules in inclusion complex was investigated. The inclusion behavior was discussed by molecular docking method and calculation of related thermodynamic parameters. The results showed that when the ratio of FMN to 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) was 1: 1, the temperature was 50 ℃, The FMN-2-HP-β-CD inclusion complex was prepared under the condition of β-CD concentration of 5 g / L. The drug loading was confirmed to be 9.42 ± 0.25% The thermodynamic parameters showed that inclusion of FMN and 2-HP-β-CD was a process of exothermic and entropy reduction with enthalpy change as the main driving force. Molecular simulation showed that FMN was The 7-OH moiety enters the lumen from the bulky end of 2-HP-β-CD and forms 1 hydrogen bond with the oxygen atom on 2-HP-β-CD. Conclusions The FMN-2-HP-β-CD inclusion complex prepared in this study has good reproducibility and can improve the solubility of FMN. The inclusion complex of FMN and 2-HP-β-CD is in good agreement with the thermodynamic parameters.