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目的:研究大豆异黄酮磺酸酯化学修饰物的理化性质,并预测其药代动力学性质。方法:建立高效液相色谱法进行药物的理化性质测试和体外水解动力学试验。结果:大豆苷元-7,4′-二苯磺酸酯(DBS1)和大豆苷元-7-苯磺酸酯(DBS2)的脂溶性与水溶性相对于原药大豆苷元(DZ)均有显著的提高,脂水分配系数分别为:3.57±0.75和1.97±0.45;水解反应半衰期分别为2.14 h和19.25 h。DBS1的水解反应中4′-的磺酸酯基更易断裂。结论:化合物DBS1和DBS2的脂溶性、水溶性、脂水分配系数、熔点、极性表面积等影响药物药代动力学的一些主要性质得以优化,预示这2个化合物可能有相对较好的过膜吸收性与转运分布特性,以及良好的口服生物利用度。
Objective: To study the physicochemical properties of soy isoflavone sulfonate chemical modification and to predict the pharmacokinetic properties. Methods: The establishment of high performance liquid chromatography for physicochemical properties of drugs and in vitro hydrolysis kinetics test. Results: The liposolubility and water solubility of daidzein-7,4’-diphenyl sulfonate (DBS1) and daidzein-7-benzene sulfonate (DBS2) The lipid partition coefficients were 3.57 ± 0.75 and 1.97 ± 0.45, respectively. The half-lives of hydrolysis reaction were 2.14 h and 19.25 h, respectively. The 4’- sulfonate group in the hydrolysis reaction of DBS1 is more susceptible to cleavage. Conclusion: The main properties of the pharmacokinetics of the compounds DBS1 and DBS2, such as lipid solubility, water solubility, lipid-water partition coefficient, melting point and polar surface area, are optimized, indicating that these two compounds may have relatively good membrane Absorption and transport distribution characteristics, and good oral bioavailability.