目的 測定木香提取物中木香烴內(nèi)酯和去氫木香內(nèi)酯的平衡溶解度及表觀油水分配系數(shù)，為木香提取物新劑型研究提供實驗依據(jù)。方法 分別采用飽和溶液法和搖瓶法，使用高效液相色譜（HPLC）法測定木香烴內(nèi)酯和去氫木香內(nèi)酯的濃度，以計算木香乙醇提取物中木香烴內(nèi)酯和去氫木香內(nèi)酯在不同體積分數(shù)乙醇、丙二醇、甘油、聚乙二醇（PEG）、不同pH值磷酸鹽緩沖液（PBS）中的平衡溶解度和在正辛醇-不同pH值PBS液中油水分配系數(shù)。結果 37℃時，木香烴內(nèi)酯和去氫木香內(nèi)酯在水中的平溶解度分別為17.31、24.32 μg/mL；木香烴內(nèi)酯和去氫木香內(nèi)酯在乙醇、PEG、甘油、1，2-丙二醇的水溶液中平衡溶解度隨著溶劑添加比例（5%、10%、20%）的增加而增加，在20%乙醇中溶解度最大，分別為108.81、125.61 μg/mL，在5%甘油中溶解度最小，分別為31.72、42.83 μg/mL。兩者在pH 7.4和pH 9.0的磷酸鹽緩沖液中平衡溶解度分別達到最大，分別為16.63、26.14 μg/mL。兩種成分在pH7.4的磷酸鹽緩沖溶液中油水分配系數(shù)均達到最大，分別為89（logP_app=1.95）、144.30（logP_app=2.16）。結論 木香烴內(nèi)酯和去氫木香內(nèi)酯水溶性差，pH值影響兩者的平衡溶解度和表觀油水分配系數(shù)。

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

天津市救援醫(yī)學臨床醫(yī)學研究中心（15ZXLCSY00040）；現(xiàn)代中藥創(chuàng)新中心創(chuàng)新能力建設項目