延胡索乙素与β-环糊精及其衍生物的包合行为研究  

Study on inclusion behavior and properties of tetrahydropalmatine with β-cyclodextrin and its derivatives

作　　者：赵芳 杨云汉 赵雪秋 杨俊丽 杨丽 叶艳青 陈文[2] 杨丽娟 ZHAO Fangl;YANG Yun-han;ZHAO Xue-qiu;YANG Jun-li;YANG Li;YE Yan-qingl;CHEN Wen;YANG Li-juanl(Key Laboratory of Ethnic Medicine Resource Chemistry,State Ethnic Affairs Commission ＆ Ministry of Education,School of Chemistry and Environment,Yunnan Minzu University,Kunming 650500,China;Key Laboratory of Medicinal Chemistry for Natural Resource,Ministry of Education,Yunnan University,Kunming 650091,China)

机构地区：[1]云南民族大学化学与环境学院/民族药资源化学国家民委-教育部重点实验室,云南昆明650500 [2]云南大学教育部自然资源药物化学重点实验室,云南昆明650091

出　　处：《中草药》2018年第15期3609-3618,共10页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目资助(21762051;21562048)

摘　　要：目的制备延胡索乙素与β-环糊精及其衍生物的包合物,并对其包合行为和性能进行研究。方法通过饱和溶液法制备了延胡索乙素(THP)与β-环糊精(β-CD)、羟丙基-β-环糊精(HP-β-CD)、二甲基-β-环糊精(DM-β-CD)和三甲基-β-环糊精(TM-β-CD)的包合物;采用Job曲线法和紫外-可见光谱滴定法确定包合物的包合比和稳定常数;利用X射线粉末衍射(XRD)、热重分析(TG)和扫描电子显微镜(SEM)对包合物进行表征;运用分子对接探讨了THP与β-CD及其衍生物的包合模式;测定了包合物的水溶性,在模拟人体胃液和肠液环境下进行了稳定性测试。结果 THP与β-CD及其衍生物的包合比均为1∶1;分子对接表明,THP从大口端进入并贯穿在β-CD和DM-β-CD的空腔中,THP的2个芳香环分别位于大口端和小口端;而对于HP-β-CD和TM-β-CD来说,THP的2个氮杂环呈"V"字型镶嵌到环糊精的空腔内,且2个芳香环都位于环糊精的大口端。结论 THP与β-CD、HP-β-CD、DM-β-CD和TM-β-CD形成包合物后,其溶解度从0.30 mg/m L分别提高到了1.60、3.40、9.13、4.02 mg/m L,且其热稳定性及生物环境稳定性都得到明显提高。Objective To prepare tetrahydropalmatine（THP） and β-cyclodextrin（β-CD） and its derivatives inclusion complexes（HP-β-CD, DM-β-CD, and TM-β-CD and explore their inclusion behavior and properties. Methods The inclusion complexes of THP with β-CD, HP-β-CD, DM-β-CD, and TM-β-CD were prepared by saturated solution. The inclusion ratio and stability constant of inclusion complexes were determined with the Job plot and UV-vis spectroscopy. The THP/CDs complexes were characterized and determinated by means of XRD, TG, and SEM. The molecular simulation was processed to investigate the inclusion behavior of THP and different CDs. The water solubility of the inclusion complexes was measured and the stability test was conducted in the simulated human gastric juice and intestinal fluid environment. Results Job plot and UV-vis spectroscopy showed that inclusion ratio of host-guest inclusion complexes was 1∶1. Molecular docking showed that the entire THP entered the macrophage port and run through the cavities of β-CD and DM-β-CD, with the two aromatic rings located at the large and small mouth, respectively. For HP-β-CD and TM-β-CD, the two nitrogen heterocycle of THP were ＂V＂ shaped inlaid into the CD cavity, and both aromatic rings were located at the large end of the CDs. Conclusion The solubility of tetrahydropalmatine was increased from 0.30 mg/m L to 1.60, 3.40, 9.13, and 4.02 mg/m L for β-CD, HP-β-CD, DM-β-CD, and TM-β-CD, respectively. The thermal stability and biological environment stability had been significantly improved.

关 键 词：延胡索乙素 β-环糊精 包合物 分子对接 水溶性 稳定性 饱和溶液法 羟丙基-Β-环糊精 二甲基-β-环糊精 三甲基-β-环糊精 Job曲线法 紫外-可见光谱滴定法 

分 类 号：R283.6[医药卫生—中药学]