β-环糊精丁烯酸酯对噻菌灵的增溶效果及其复合物的抑菌活性

Solubilization Effects of β-Cyclodextrin Butenate on Thiabendazole and Antibacterial Activities of Their Complex

摘要:

该研究通过丁烯酸同β-环糊精酯化制备β-环糊精丁烯酸酯，以提高β-环糊精在水溶液中的溶解度；以噻菌灵为疏水性药物，利用相溶解度实验考察噻菌灵同β-环糊精及其丁烯酸酯衍生物形成的复合物的表观稳定系数，并用中红外图谱对其结构进行表征。β-环糊精丁烯酸酯的合成以N,N-羰基二咪唑为羧酸活化试剂，以二甲氨基吡啶为催化剂，二甲基甲酰胺为溶剂。β-环糊精丁烯酸酯在水溶的溶解度（25 ℃）为β-环糊精的2.05倍。当水温为50 ℃时，噻菌灵同β环糊精及其丁烯酸酯衍生物形成的复合物的表观稳定系数分为59.35 M-1和52.43 M-1，两者无显著差异（p>0.05）。β-环糊精丁烯酸酯可以提高噻菌灵在水中的溶解度，且其增溶效果要优于β-环糊精。噻菌灵同β-环糊精及其丁烯酸酯衍生物形成的复合物后，噻菌灵在水中的溶解度有较大地提升，抑菌效果得到加强。

Abstract:

Thiabendazole is a hydrophobic anti-bacterial drug. However, the water solubility of thiabendazole can be significantly enhanced by its complexation with cyclodextrins. In this study, β-cyclodextrin butenate was synthesized by the esterification of butenoic acid and β-cyclodextrin to improve the solubility of β-cyclodextrin in aqueous solutions. The apparent stability coefficients of thiabendazole-β-cyclodextrin and thiabendazole-β-cyclodextrin butenate complexes were determined by phase solubility tests, and the structures of these complexes were analyzed by mid-infrared spectroscopy. β-Cyclodextrin butenate was synthesized by using N,N-carbonyldiimidazole as the carboxylic acid activation reagent, 4-dimethylaminopyridine as the catalyst, and dimethylformamide as the solvent. The solubility of β-cyclodextrin butenate in water (25 ℃) was 2.05 times that of β-cyclodextrin. At a water temperature of 50 ℃, the apparent stability coefficients of the thiabendazole-β-cyclodextrin and thiabendazole-β-cyclodextrin butenate complexes were 59.35 and 52.43 M-1, respectively; no significant difference was observed between them (p>0.05). β-Cyclodextrin butenate could improve the solubility of thiabendazole in water upon complexation, and its solubilization effect is stronger than that of β-cyclodextrin. The solubility of thiabendazole in water is considerably improved, and the thiabendazole-β-cyclodextrin and thiabendazole-β-cyclodextrin butenate complexes exhibit strong anti-bacterial effects.