目的 研究3种沉淀抑制剂（PPI）羟丙基甲基纤维素K4M（Hydroxypropyl methyl cellulose K4M，HPMC K4M）、醋酸羟丙甲纤维素琥珀酸酯MG（Hypromellose Acetate Succinate MG，HPMC AS MG）、聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物（Polyvinylpyrrolidone，Soluplus）对临床口服剂量下pH值诱导延胡索乙素（dl-THP）过饱和相行为的影响。方法 绘制dl-THP的pH值-溶解度相图和pH值转换过程中的去过饱和曲线，用溶解度相图佐证dl-THP相行为，以质量浓度-时间曲线下面积和过饱和度为指标分析沉淀抑制剂对dl-THP相行为的影响；采用偏振光显微镜、差示扫描量热法分析沉淀性质。结果 临床给药剂量下，dl-THP在pH值转换过程中最大过饱和度为3.93，随时间推移失去过饱和；HPMC K4M、HPMC AS MG、Soluplus在pH值转换180 min内均能维持过饱和度。HPMC K4M、HPMC AS MG、Soluplus在浓度5%时维持过饱和度分别为1.19、1.89、1.36，浓度20%时为1.30、2.35、1.86、浓度50%时为1.30、2.60、2.07。偏振光显微镜和差示扫描量热法结果表明产生结晶沉淀。结论 沉淀抑制剂均能改善pH值诱导延胡索乙素过饱和相行为，且这种改善行为随沉淀抑制剂种类和浓度的不同而不同，HPMC AS MG作用效果最佳。

Objective To investigate the effect of three types of precipitation inhibitors (PPI) HPMC K4M, HPMC AS MG and Soluplus on the pH-induced supersaturated phase behavior of dl-tetrahydropalmatine (dl-THP) at oral clinical doses. Methods dl-THP pH solubility phase diagram and desaturation curve during pH-shift were drawn, and the solubility phase diagram was used to support dl-THP phase behavior. Area under the concentration-time curve and supersaturation ratio were used to analyze the effect of PPI on the phase behavior of dl-THP; Polarized light microscope and differential scanning calorimetry were used to analyze the precipitation properties. Results Under the clinical dosage, the maximum supersaturation of dl-THP during the pH-shift was 3.93, and the supersaturation was lost over time; HPMC K4M, HPMC AS MG, and Soluplus could all maintain the supersaturation within 180 minutes during the pH-shift dissolution. HPMC K4M, HPMC AS MG, and Soluplus maintained supersaturation levels of 1.19, 1.89 and 1.36 respectively at a concentration of 5%, 1.30, 2.35 and 1.86 at a concentration of 20%, and 1.30, 2.60 and 2.07 at a concentration of 50%. Polarized light microscopy and differential scanning calorimetry results showed that crystalline precipitation occurred. Conclusion All precipitation inhibitors can improve the pH-induced supersaturated phase behavior of tetrahydropalmatine, and this improvement behavior varies with the type and concentration of precipitation inhibitors. HPMC AS MG has the best effect.

R283.6

江西省一流学科资助（JXSYLXK-ZHYAO059）