周江　吴婷婷　李美云　雷小小　唐婷　桂卉

摘要：目的 优选莲心碱羟丙基-β-环糊精（HP-β-CD）包合物的最佳制备工艺，考察莲心碱HP-β-CD包合物体外溶出性质。方法 采用饱和水溶液法制备包合物，以45 min体外累积溶出度为指标，采用三因素三水平Box-Behnken设计，考察HP-β-CD与莲心碱投料比、搅拌时间、包合温度对制备工艺的影响，对结果进行多元线性和二项式拟合，效应面法筛选出最佳包合工艺，进行预测分析和验证试验，并应用显微电镜扫描法、差示量热扫描法、红外光谱、X射线衍射法对包合物进行结构表征。结果 莲心碱HP-β-CD包合物的最佳制备工艺为：HP-β-CD用量为莲心碱投料量的4.5倍，搅拌时间为3.7 h，包合温度为52 ℃。表征鉴定结果显示莲心碱HP-β-CD包合物已形成。结论 本研究优选的最佳包合工艺稳定可行，能显著提高莲心碱的溶出度，增加其生物利用度。

关键词：莲心碱；羟丙基-β-环糊精；包合物；Box-Behnken设计-效应面法；累积溶出度

DOI：10.3969/j.issn.1005-5304.2016.03.022

中图分类号：R283.5 文献标识码：A 文章编号：1005-5304（2016）03-0080-05

Abstract： Objective To optimize the preparation of liensinine HP-β-CD inclusion compound； To investigate its dissolution performance in vitro. Methods The inclusion compound of liensinine was prepared by using saturated water solution method； the cumulative dissolution （45 min） was used as an indicator and Box-Behnken design was adopted to evaluate the influence of feed ratio， mixing time and inclusion temperature on preparation process. Results were analyzed by multiple linear and binomial fitting； response surface methodology was used to screen the optimal inclusion process； predictive parsing and verification experiment were conducted； SEM， DSC， IR， and XRD were applied for the structural characterization of inclusion compound of liensinine. Results The optimal preparation process was： HP-β-CD was 4.5 times the amount of liensinine feeding amount； mixing time was 3.7 h； inclusion temperature was 52 ℃. HP-β-CD inclusion compound of liensinine formed. Conclusion Optimal inclusion process is stable and feasible， which can significantly improve the dissolution of liensinine and increase its bioavailability.

Key words： liensinine； HP-β-CD； inclusion compound； Box-Behnken design； cumulative dissolution

莲心碱（liensinine）是中药莲子心中含量较高的一种双苄基异喹啉类生物碱，具有降压、抗心律失常、抗氧化、对抗血栓形成等作用[1-3]，具有良好的开发应用前景。但莲心碱在水中溶解度差，口服溶出速率较慢，极大地限制其临床应用。通过增加其在体外的溶出速率有望提高莲心碱在体内的生物利用度。包合技术具有增加药物溶解度、降低药物刺激性、减少毒性、提高药物稳定性、提高生物利用度等优点[4-5]。本研究采用相溶解度法考察羟丙基-β-环糊精（HP-β-CD）对莲……