目的 测定木香提取物中木香烃内酯和去氢木香内酯的平衡溶解度及表观油水分配系数，为木香提取物新剂型研究提供实验依据。方法 分别采用饱和溶液法和摇瓶法，使用高效液相色谱（HPLC）法测定木香烃内酯和去氢木香内酯的浓度，以计算木香乙醇提取物中木香烃内酯和去氢木香内酯在不同体积分数乙醇、丙二醇、甘油、聚乙二醇（PEG）、不同pH值磷酸盐缓冲液（PBS）中的平衡溶解度和在正辛醇-不同pH值PBS液中油水分配系数。结果 37℃时，木香烃内酯和去氢木香内酯在水中的平溶解度分别为17.31、24.32 μg/mL；木香烃内酯和去氢木香内酯在乙醇、PEG、甘油、1，2-丙二醇的水溶液中平衡溶解度随着溶剂添加比例（5%、10%、20%）的增加而增加，在20%乙醇中溶解度最大，分别为108.81、125.61 μg/mL，在5%甘油中溶解度最小，分别为31.72、42.83 μg/mL。两者在pH 7.4和pH 9.0的磷酸盐缓冲液中平衡溶解度分别达到最大，分别为16.63、26.14 μg/mL。两种成分在pH7.4的磷酸盐缓冲溶液中油水分配系数均达到最大，分别为89（logP_app=1.95）、144.30（logP_app=2.16）。结论 木香烃内酯和去氢木香内酯水溶性差，pH值影响两者的平衡溶解度和表观油水分配系数。

Objective To measure the equilibrium solubility and the oil-water partition coefficients of costunolide and dehydrocostusactone in Aucklandia lappa Decne. extract. Methods The oil-water partition coefficients in different volume fractions of ethanol, propylene glycol, glycerin, polyethylene glycol (PEG), phosphate buffer (PBS) with different pH value, and equilibrium solubility in N-octanol-phosphate buffer with different pH of costunolide and dehydrocostusactone was determined by shake-flask method and saturated aqueous solution method. The concentration of costunolide and dehydrocostusactone were analyzed by HPLC method. Results Under the temperature of 37℃,the equilibrium solubility of costunolide and dehydrocostusactone in water is 17.31 μg/mL, and 24.32 μg/mL, respectively. The equilibrium solubility of costunolide and dehydrocostusactone in ethanol, PEG, glycerol and propylene glycol increased with the increase of the proportion of solvent addition (5%, 10%, 20%). And the highest solubility was found in 20% ethanol, the equilibrium solubility of costunolide and dehydrocostusactone in 20% ethanol were 108.81 μg/mL, and 125.61 μg/mL. The lowest was found in 5% glycerol, the equilibrium solubility of costunolide and dehydrocostusactone in 5% glycerol were 31.72 μg/mL and 42.83 μg/mL. The equilibrium solubility of costunolide and dehydrocostusactone reached the maximum at pH7.4 and pH9.0, which were 16.63 μg/mL and 26.14 μg/mL, respectively. The oil-water partition coefficients of costunolide and dehydrocostusactone were similar and reached the highest at pH7.4, which were[89 (logP_app=1.95)] and[144.30 (logP_app=2.16)], respectively. Conclusion The water solubility of costunolide and dehydrocostusactone are poor, and the pH value affects the equilibrium solubility and apparent oil-water distribution coefficient of costunolide and dehydrocostusactone.

R944.9

天津市救援医学临床医学研究中心（15ZXLCSY00040）；现代中药创新中心创新能力建设项目