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目的以木犀草苷、迷迭香酸和田蓟苷为指标,检测香青兰提取物(EDM)及其指标成分在不同溶剂和助溶剂中的质量浓度和不同p H值下的表观油水分配系数(P)及其体外胃肠液中的稳定性,为今后新剂型的选择和制备提供参考。方法采用沉淀法测定提取物在不同溶剂和表面活性剂溶液中的平衡溶解度,采用摇瓶法测定其在正辛醇-水及磷酸缓冲盐中的P,并考察其在体外胃肠液中的稳定性。采用HPLC测定指标成分的量,色谱柱为Shim-pack ODS(250 mm×4.6 mm,5μm),流动相为乙腈-0.5%甲酸水溶液,梯度洗脱:0~30 min,15%乙腈;30~55 min,15%~25%乙腈;55~80 min,25%~35%乙腈;体积流量1.0 m L/min,检测波长324 nm,柱温35℃。结果在37℃时,提取物(3个指标成分)在酸性缓冲溶液中的平衡溶解度均有明显降低,在碱性缓冲液中随p H值的增高平衡溶解度逐渐增加。在32 g/L的十二烷基硫酸钠(SDS)溶液中木犀草苷、迷迭香酸和田蓟苷的平衡溶解度分别提高到1 679.61、1 249.20、2 765.27μg/m L,增溶效果最好。EDM(3种成分)的P分别为0.173 1(lg P=-0.761 8)、0.068 4(lg P=-1.165 0)和1.082 9(lg P=0.034 6),且随溶液p H值的升高逐渐增加。三者均在人工肠液中稳定,除木犀草苷以外,均在人工胃液中稳定。结论建立的方法可准确测定EDM及其指标成分的溶解度和P等,同时,在体外胃肠液环境中较稳定,为EDM今后的新剂型设计提供实验参考。
OBJECTIVE To determine the apparent oil-water distribution under the different concentrations of p-toluenesulfonic acid and different concentrations of p-toluenesulfonic acid and luteolin, rosmarinic acid and thymidine in EDM and its index components Coefficient (P) and its stability in vitro gastrointestinal fluid for the future selection and preparation of new formulations provide a reference. Methods The equilibrium solubility of the extract in different solvents and surfactant solutions was determined by precipitation method. The P in n-octanol-water and phosphate buffered saline was determined by shake flask method and its in vitro gastrointestinal fluid stability. The mobile phase consisted of acetonitrile-0.5% formic acid in water with gradient elution: 0 ~ 30 min, 15% acetonitrile and 30 ~ 55 min, 25% -35% acetonitrile, volume flow rate 1.0 m L / min, detection wavelength 324 nm and column temperature 35 ℃. Results At 37 ℃, the equilibrium solubility of extracts (three index components) in acid buffer solution decreased obviously. The equilibrium solubility gradually increased with the increase of p H value in alkaline buffer solution. In 32 g / L sodium dodecyl sulfate (SDS) solution, the equilibrium solubilities of luteolin, rosmarinic acid and thymidine were increased to 1 679.61, 1 249.20 and 2 765.27 μg / ml, respectively. The solubilization effect the best. P of EDM (3 components) were 0.173 1 (lg P = -0.761 8), 0.068 4 (lg P = -1.165 0) and 1.082 9 (lg P = 0.034 6) High gradually increased. All three were stable in artificial intestinal juice except for luteolin, which were all stable in artificial gastric juice. Conclusion The established method can accurately determine the solubility and P, etc. Of EDM and its index components, meanwhile, it is stable in vitro in gastrointestinal fluid environment, providing experimental reference for the design of new dosage forms of EDM in the future.