Ikeda Yoichi, Motoune Sohko, Matsuoka Toshikazu, Arima Hidetoshi, Hirayama Fumitoshi, Uekama Kaneto
Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Takata-gun, Hiroshima 739-1195, Japan.
J Pharm Sci. 2002 Nov;91(11):2390-8. doi: 10.1002/jps.10232.
The inclusion complex formation of alpha-cyclodextrin (alpha-CyD), beta-cyclodextrin (beta-CyD), and 2-hydroxylpropyl-beta-cyclodextrin (HP-beta-CyD) with an angiotensin converting enzyme inhibitor, captopril, in aqueous solution was studied by (1)H- and (13)C-nuclear magnetic resonance spectroscopies, including ROESY and GROESY techniques, by kinetic methods and by molecular dynamic calculations. The oxidative degradation of captopril was markedly suppressed in alpha-CyD solutions, whereas beta-CyD and HP-beta-CyD had negligible stabilizing effects. These NMR and kinetic results suggested that alpha-CyD includes preferably the propyl thioalcohol moiety of captopril, depositing the proline moiety outside the cavity. On the other hand, beta-CyD includes a whole molecule of captopril in the cavity, locating the carboxylic acid within the cavity and the terminal thiol moiety outside the cavity. These inclusion structures were supported by molecular dynamic studies.
通过（1）H和（13）C核磁共振光谱（包括ROESY和GROESY技术）、动力学方法以及分子动力学计算，研究了α-环糊精（α-CyD）、β-环糊精（β-CyD）和2-羟丙基-β-环糊精（HP-β-CyD）与血管紧张素转换酶抑制剂卡托普利在水溶液中的包合物形成情况。在α-CyD溶液中，卡托普利的氧化降解明显受到抑制，而β-CyD和HP-β-CyD的稳定作用可忽略不计。这些核磁共振和动力学结果表明，α-CyD优先包含卡托普利的丙基硫醇部分，脯氨酸部分沉积在腔体外。另一方面，β-CyD在腔内包含整个卡托普利分子，羧酸位于腔内，末端硫醇部分位于腔体外。这些包合结构得到了分子动力学研究的支持。
