染料木素的小肠吸收与体内活性相关性的研究

Studies on the Relationship Between the Intestinal Absorption and the in vivo Activity of Genistein

目的:通过提高染料木素的溶解度和渗透速率来改善染料木素的小肠吸收及体内活性。方法:运用热力学溶解度测定方法测定染料木素于水及不同pH水溶液中的溶解度,考察表面活性剂泊洛沙姆F-68和十二烷基磺酸钠及亲水性高分子辅料PEG-6000、PVP K30和羟丙基-β-环糊精对它溶解度的影响。利用非翻转大鼠小肠囊模型测定染料木素的渗透系数,考察不同类型的吸收促进剂对它通透性的影响。利用D-半乳糖致亚急性衰老模型小鼠考察增溶增渗剂对染料木素体内活性的影响。结果:染料木素在水及不同pH水溶液中的溶解度<18μg·ml-1,不同浓度的羟丙基-β-环糊精使它的溶解度显著提高。染料木素于大鼠小肠的渗透系数为2·36×10-6cm·s-1,不同类型的吸收促进剂均能使染料木素的渗透系数增加,促吸效果为:0·5%脱氧胆酸钠>0·5%十二烷基磺酸钠>0·5%乙二胺四乙酸二钠>0·5%泊洛沙姆F-68>0·5%吐温80>0·5%羧甲基壳聚糖。体内试验结果表明,增溶后的染料木素较增溶前的染料木素的体内活性有显著性差异,增溶增渗后的染料木素较仅增溶的染料木素的体内活性有显著性差异。结论:以溶解度及渗透系数为指标改善染料木素的小肠吸收能够改善它的体内抗衰老活性。

AIM： To improve the in vivo activity of genistein by increasing the solubility and permeability of genistein. METHOD： Determining the solubility of genistein in water and water solution with different pH, evaluating the influence of F68, SDS, PEG-6000, PVP K30 and HPβCD on the solubility of genistein. Determining the permeability of genistein across the rat intestinal mucosa by noneverted gut sacs models and exploring the effects of various absorption enhancers on the permeability of genistein. Determining the MDA level in brain of aging mice induced by overdose D-galactose to show the different antioxidation efficiency of genistein with/without solubilizer and enhancer in vivo. RESULT： The solubility of genistein in water and water solution at different pH is 〈 18 μg·ml^-1, extremely increased by HPβCD. The permeability of genistein across the rat intestine was 2.36 × 10^-6 cm·s^-1, enhanced by adding various absorption enhancers. The enhancement rate was as follows：0.5% DOC 〉 0.5% SDS 〉 0.5% EDTA-2Na 〉 0.5% F-68 〉 0.5% Tween- 80〉 0.5% MCC. In the aging mice induced by overdose of D-galactose, the antioxidation effect of genistein combined with solubilizer and absorption enhancer displayed better than genistein suspension solution with a corresponding dosage without solubilizer and enhancer. CONCLUSION： The in vivo antiaging activity of genistein can be improved by increasing the solubility and permeability of genistein.