Uekama K, Horikawa T, Yamanaka M, Hirayama F
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
J Pharm Pharmacol. 1994 Sep;46(9):714-7. doi: 10.1111/j.2042-7158.1994.tb03889.x.
Peracylated beta-cyclodextrins with different alkyl chains (acetyl-octanoyl) were prepared by acylating all hydroxyl groups of beta-cyclodextrin (beta-CyD), and their physical properties were evaluated. These hydrophobic beta-CyDs decreased the release rate of molsidomine, a peripheral vasodilator, in proportion to the lengthening of alkyl chain and suppressed a peak plasma level of molsidomine following oral administration of peracylated beta-CyD complexes to dogs. Among the peracylated beta-CyDs tested, perbutanoyl-beta-CyD maintained sufficient plasma drug levels for a long period of time, while other peracylated beta-CyDs having shorter or longer chains were inappropriate to control the in-vivo release behaviour of molsidomine. The prominent retarding effect of perbutanoyl-beta-CyD was ascribable to the appropriate mucoadhesive property and hydrophobicity, compared with other peracylated beta-CyDs. The present results suggest that perbutanoyl-beta-CyD is particularly useful in modifying the release rate of water-soluble drugs as a novel slow-release carrier.
通过对β-环糊精（β-CyD）的所有羟基进行酰化反应，制备了具有不同烷基链（乙酰基-辛酰基）的过酰化β-环糊精，并对其物理性质进行了评估。这些疏水性β-环糊精降低了外周血管扩张剂吗多明的释放速率，其降低程度与烷基链的长度成正比，并且在给狗口服过酰化β-环糊精复合物后，抑制了吗多明的血浆峰值水平。在所测试的过酰化β-环糊精中，过丁酰基-β-环糊精能长时间维持足够的血浆药物水平，而其他链长较短或较长的过酰化β-环糊精则不适用于控制吗多明的体内释放行为。与其他过酰化β-环糊精相比，过丁酰基-β-环糊精显著的缓释作用归因于其适当的粘膜粘附性和疏水性。目前的结果表明，过丁酰基-β-环糊精作为一种新型缓释载体，在调节水溶性药物的释放速率方面特别有用。
