6-O-α-D-半乳糖基-和6-O-α-D-甘露糖基-环糊精的性质及包合行为

Properties and the inclusion behavior of 6-O-alpha-D-galactosyl- and 6-O-alpha-D-mannosyl-cyclodextrins.

作者信息

Okada Y, Matsuda K, Hara K, Hamayasu K, Hashimoto H, Koizumi K

机构信息

School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1999 Nov;47(11):1564-8. doi: 10.1248/cpb.47.1564.

DOI:10.1248/cpb.47.1564

PMID:10605055

Abstract

The novel heterogeneous branched cyclodextrins (CDs), 6-O-alpha-D- galactosyl-alpha, -beta, and -gamma CDs (Gal-alpha, -beta, and -gamma CDs) and 6-O-alpha-D-mannosyl-alpha, -beta, and -gamma CDs (Man-alpha, -beta, and -gamma CDs) dissolved sufficiently in water and in 10-50% (v/v) methanol aqueous solutions, as did the homogeneous branched CDs, 6-O-alpha-D-glucosyl-alpha, -beta, and -gamma CDs (Glc-alpha, -beta, and -gamma CDs). The solubilities of heterogeneous branched CDs were higher than those of each parent non-branched CDs. The hemolytic activities of heterogeneous and homogeneous branched CDs were lower than those of each parent non-branched CDs and the hemolytic activity became weaker in the order of non-branched CD > Man-CD > Glc-CD > Gal-CD in each series of alpha, beta, and gamma CD. AL type solubility-phase diagrams were displayed in the formation of inclusion complexes of the guest compounds of small size (methyl benzoate, estriol, and dexamethasone) with Gal-, Man-, and Glc-CDs, and marked differences among the three kinds of branched CDs could not be detected. However, solubility-phase diagrams between these branched CDs and the insoluble guest compounds of large cyclic structure (cyclosporin A, tacrolimus, and amphotericin B) showed AP type, and the improvement of water solubilities of these guest compounds with three kinds of branched CDs was enhanced in the order of Man-CDs > Glc-CDs > Gal-CDs.

摘要

新型异质支链环糊精（CDs），即6-O-α-D-半乳糖基-α、-β和-γ环糊精（Gal-α、-β和-γ环糊精）以及6-O-α-D-甘露糖基-α、-β和-γ环糊精（Man-α、-β和-γ环糊精），与同质支链环糊精6-O-α-D-葡萄糖基-α、-β和-γ环糊精（Glc-α、-β和-γ环糊精）一样，能充分溶解于水以及10 - 50%（v/v）的甲醇水溶液中。异质支链环糊精的溶解度高于各自的母体非支链环糊精。异质和同质支链环糊精的溶血活性均低于各自的母体非支链环糊精，并且在α、β和γ环糊精的每个系列中，溶血活性按非支链环糊精>甘露糖基环糊精>葡萄糖基环糊精>半乳糖基环糊精的顺序减弱。在小分子客体化合物（苯甲酸甲酯、雌三醇和地塞米松）与Gal-、Man-和Glc-环糊精形成包合物时呈现出AL型溶解度相图，且未检测到这三种支链环糊精之间有明显差异。然而，这些支链环糊精与大环状结构的不溶性客体化合物（环孢素A、他克莫司和两性霉素B）之间的溶解度相图显示为AP型，并且这三种支链环糊精对这些客体化合物水溶性的改善程度按Man-环糊精>Glc-环糊精>Gal-环糊精的顺序增强。