Stoichiometry-dependent changes of solubility and photoreactivity of an antiulcer agent, 2′-carboxymethoxy-4,4′-bis(3-methyl-2-butenyloxy) chalcone, in cyclodextrin inclusion complexes
Stoichiometry-dependent changes of solubility and photoreactivity of an antiulcer agent, 2′-carboxymethoxy-4,4′-bis(3-methyl-2-butenyloxy) chalcone, in cyclodextrin inclusion complexes
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环糊精包合物中抗溃疡剂 2-羧甲氧基-4,4-双（3-甲基-2-丁烯氧基）查尔酮的溶解度和光反应性的化学计量依赖性变化
DOI：
10.1016/0928-0987(93)90021-2
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
K. Uekama
中科院分区：
文献类型：
--
作者：
T. Utsuki;K. Imamura;F. Hirayama;K. Uekama
抗溃疡药物2′-羧甲氧基-4，4 ′-双（3-甲基-2-丁烯氧基）查耳酮（CBC）与α-、β-和γ-环糊精（α-、β-和γ-CyDs）在水溶液中以1：1和1：2的摩尔比形成包合物。CBC的低水溶性（1.1 × 10− 5 M）通过CyD络合物显著改善，增强效果的程度取决于络合物的化学计量。化学计量比为1：2的α-和β-CyD复合物在水中的溶解度高于相应的1：1复合物，而1：2 γ-CyD复合物的溶解度低于1：1复合物，因为CBC完全包含在水合程度较低的γ-CyD二聚体中。1：1和1：2复合物显示出不同的光反应性，即，在1：1络合物中，由于空间位阻效应，CBC的（E）-（Z）光异构化速度减慢，而在1：2络合物中，由于微溶剂效应，CBC的（E）-（Z）光异构化速度加快。在相溶解度图的基础上，制备了化学计量比为1：2的β-和γ-CyD CBC固体配合物，并研究了它们的溶解行为。β-CyD络合物的溶解速率远快于γ-CyD络合物，这可能是由于1：2 γ-CyD络合物的溶解度和润湿性较低所致。目前的数据表明，物理化学性质，如溶解度和反应性，CyD复合物的化学计量的变化，因此CyD浓度应优化CBC配方的合理设计。
An antiulcer agent, 2′-carboxymethoxy-4,4′-bis(3-methyl-2-butenyloxy) chalcone (CBC), formed inclusion complexes with α-, β- and γ-cyclodextrins (α-, β- and γ-CyDs) in molar ratios (guest:host) of 1:1 and 1:2 in water. The low aqueous solubility of CBC (1.1 × 10−5M) was significantly improved by CyD complexations, the degree of the enhancing effect differing depending on the stoichiometry of the complexes. The α- and β-CyD complexes with a stoichiometry of 1:2 have higher solubilities in water than the corresponding 1:1 complexes, whereas the solubility of the 1:2 γ-CyD complex was lower than that of the 1:1 complex because of the complete inclusion of CBC in a γ-CyD dimer which is less hydrated. The 1:1 and 1:2 complexes showed different photoreactivities, i.e., the (E)-(Z) photoisomerization of CBC was decelerated in the 1:1 complex due to the steric effect, while rather accelerated in the 1:2 complex due to the microsolvent effect. The β- and γ-CyD solid complexes of CBC with a 1:2 stoichiometry were prepared on the basis of the phase solubility diagram, and their dissolution behaviors were investigated. The dissolution rate of the β-CyD complex was much faster than that of the γ-CyD complex, probably due to the lower solubility and wettability of the 1:2 γ-CyD complex. The present data indicated that physicochemical properties, such as solubility and reactivity, of CyD complexes are changed depending on the stoichiometry, and thus CyD concentrations should be optimized for a rational design of CBC formulation.
DOI：
10.1248/bpb1978.4.879
发表时间：
1981-01-01
期刊：
JOURNAL OF PHARMACOBIO-DYNAMICS
影响因子：
--
作者：
YAMAOKA, K;TANIGAWARA, Y;UNO, T
通讯作者：
UNO, T