【摘要】 目的 制备姜黄素自胶束化固体分散体，并考察其体内药动学。方法 溶剂蒸发法制备自胶束化固体分散体，测定其累积溶出率、饱和溶解度、稳定性、理化性质、自胶束化性能。12只大鼠随机分为2组，分别灌胃给予姜黄素及其自胶束化固体分散体的0.5%CMC-Na混悬液（100 mg/kg）,于0.083、0.167、0.25、0.5、0.75、1、2、3、4、6、8、12、24 h采血，UPLC法测定姜黄素血药浓度，计算主要药动学参数。结果 自胶束化固体分散体呈圆球形，表面光滑，分散均匀，无粘连，60 min内累积溶出率为（90.31±2.24）%,饱和溶解度为（583.17±16.78）μg/mL,粒径为22 nm, PDI为0.048,Zeta电位绝对值为1.2,在6个月内稳定性良好。姜黄素以无定形状态存在，与载体（F127、TPGS）之间可能发生氢键效应。与原料药比较，自胶束化固体分散体C_max、AUC_0～t、AUC_0～∞升高（P<0.01）,t_max、t_1/2延长（P<0.01）,相对生物利用度增加至7.05倍。结论 自胶束化固体分散体可改善姜黄素体外溶出度、体内生物利用度。更多还原

【Abstract】 AIM To prepare curcumin self-micellizing solid dispersions and to investigate their in vivo pharmacokinetics.METHODS Solvent evaporation method was adopted in the preparation of self-micellizing solid dispersions, after which the accumulative dissolution rate, saturated solubility, stability, physicochemical properties and self-micellizing properties were determined. Twelve rats were randomly assigned into two groups and given intragastric administration of the 0.5%CMC-Na suspensions of curcumin and its self-micellizing solid dispersions（100 mg/kg）, respectively, after which blood collection was made at 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 24 h, UPLC was adopted in the plasma concentration determination of curcumin, and main pharmacokinetic parameters were calculated.RESULTS The spherical self-micellizing solid dispersions demonstrated smooth surfaceand uniform dispersion without adhension, whose accumulative dissolution rate within 60 min, saturated solubility, particle size, PDI, absolute value of Zeta potential were（90.31±2.24）%,（583.17±16.78） μg/mL, 22 nm, 0.048 and 1.2, respectively, along with good stability within 6 months. Curcumin existed in an amorphous state, which might occured hydrogen-bonding effect between carriers（F127, TPGS）. Compared with raw medicine, the self-micellizing solid dispersions displayed increased C_max, AUC_0-t, AUC_0-∞（P<0.01）, and prolonged t_max, t_1/2（P<0.01）, the relative bioavailability was enhanced to 7.05 times.CONCLUSION Self-micellizing solid dispersion can improve the in vitro dissolution rate and in vivo bioavailability of curcumin.更多还原