白杨素平衡溶解度、油水分配系数及解离常数的测定

目的：测定白杨素在不同介质中的平衡溶解度以及其在水和不同pH溶液中的油水分配系数（lgP）和解离常数（pK_a）。方法：采用高效液相色谱法测定白杨素在不同介质中的平衡溶解度；采用摇瓶法测定白杨素在水和不同pH溶液中的lgP；采用紫外分光光度法测定白杨素的pK_a。结果：37℃时，白杨素在水中的平衡溶解度为38.43 μg·L^-1，lgP为4.37；白杨素在pH为1.2~9的溶液中，平衡溶解度和lgP无明显变化，当pH达到10和11时，平衡溶解度和lgP变化明显；实验测得，白杨素在常用油相中的平衡溶解度均小于0.5 g·L^-1，而在非醇类的表面活性剂Transcutol HP中溶解度最大为6.63 g·L^-1；白杨素的2个解离常数pK_a1、pK_a2分别为6.52、7.92。结论：白杨素具有极差的水溶性，为弱酸性药物，其解离过程分为两步进行。

Obstractive: To measure the equilibrium solubility in different mediums,the oil-water partition coefficients in water and other buffer solutions with different pH values and dissociation constant of chrysin.Methods: An HPLC was employed to measure the equilibrium solubility of chrysin in different solvents.Flask shaking method was adopted to measure the oil-water partition coefficients in water and other buffer solutions with different pH values of chrysin.UV spectrophotometry was used to measure the dissociation constant.Results: Under the temperature of 37℃,the equilibrium solubility of chrysin in water is 38.43 μg·L^-1,and the lgP was 4.37.When in the buffer solution with the pH value of 1.2-9,its equilibrium solubility and lgP had no significant change,and when the pH value reached 10 and 11,the equilibrium solubility and lgP change obviously.All equilibrium solubility values of chrysin in common oil phases were less than 0.5 g·L^-1,while its largest solubility value in non-alcohol surfactant Transcutol HP was 6.63 g·L^-1.The two dissociation constants of chrysin,pK_a1 and pK_a2 were 6.52 and 7.92,respectively.Conclusion: Chrysinit has a poor water solubility and is a weak acid drug.Its dissociation process is divided into two steps.