β-环糊精与二氢吡啶类药物的相互作用  

Study on inclusion interaction of β-CD with 1,4-dihydropyridine derivates

作　　者：武雪芬[1] 郑晓珂[1] 孙德梅[1] 李桂兰[2] 

机构地区：[1]河南中医学院药学院,河南郑州450008 [2]郑州大学化学系,河南郑州450052

出　　处：《中国药学杂志》2005年第8期599-601,共3页Chinese Pharmaceutical Journal

基　　金：河南省科技厅(0424410105)教育厅资助项目(2004360005)

摘　　要：目的研究β-环糊精(β-CD)对二氢吡啶类药物硝苯地平、尼群地平、尼莫地平的包合作用和分子识别能力。方法由包合反应得率确定反应的平衡位置,并以此评价β-CD对3者的包合能力;由核磁共振和差热分析证明包合物的形成。结果β-CD对药物的包合能力为硝苯地平>尼群地平,包合常数K硝苯地平=51.48 mol·L-1,K尼群地平=0.88 mol·L-1,β-CD与尼莫地平未形成包合物。结论β-CD与客体药物形成1:1型包合物;客体分子从大口端进入CD的孔腔,苯环部分停留在主体腔内,客体分子中取代基的位置和体积对包合作用有显著影响;包合态药物的熔融相变温度和热分解温度明显高于原药。OBJECTIVE: To investigate the molecular recognition of β-CD with 1,4-dihydropyridine derivates (nifedipine, nitrendipine, nimodipine). METHODS: Inclusion ability of β-CD to 1,4-dihydropyridine derivates was evaluated by determining their formation constants of inclusion complexes. RESULTS: The inclusion effect of β-CD to guest was decreased by the sequence of nifedipine > nitrendipine > nimodipine, the formation constants were K1 51.48 mol&middotL-1, K2 0.88 mol&middotL-1, and the inclusion complex of β-CD with nimodipinum was not formed. CONCLUSION: The constitute of inclusion complexes, β-CD with nifedipine and nitrendipine was 1:1, respectively. Guest entered into the lumen of β-CD from its larger port, and phenyl part rest on the lumen of β-CD. The inclusion effect of β-CD with 1,4-dihydropyridine derivates, was related to the position and the volume of the replace group of guest. The melting and the heat decomposing temperature increased obviously.

关 键 词：硝苯地平 尼群地平 尼莫地平 Β-环糊精 分子识别 

分 类 号：R969.2[医药卫生—药理学]