目的 评价克癌素结肠定位包衣滴丸有效成分姜黄素在家兔体内的药动学。方法 6只家兔随机等分成两组：受试制剂和参比制剂组，受试制剂组给予克癌素结肠定位包衣滴丸，参比制剂组给予滴丸丸芯，两组均按单剂量ig给药120丸（每丸含姜黄素1.5 mg），于给药后不同时间颈动脉取血。建立血浆中姜黄素检测的高效液相色谱（HPLC）法，并进行方法学验证；测定各时间点家兔体内姜黄素血药浓度，绘制药时曲线，DAS 2.1软件计算主要药动学参数，根据药动学参数计算受试制剂的相对利用度（Fr）。结果 建立的HPLC法的方法学试验均符合检测要求；药时曲线显示，参比制剂丸芯符合双室模型，无滞后时间，而受试制剂符合一室模型，有滞后时间；药动学参数显示，与参比制剂比较，受试制剂的统计矩参数药时曲线下面积（AUC_0-^∞）显著增大、延迟时间（t_lag）为5.307 h，显著延长（P < 0.05），参比制剂的达峰时间（t_max）为3 h，受试制剂t_max为16 h，两组差异显著（P < 0.05）。受试制剂的Fr为74.0%，其C_max为参比制剂的62.6%，二者间均不具生物等效性。结论 克癌素结肠定位包衣滴丸具有典型的缓（控）释特征，姜黄素成分结肠段蓄积，具有良好的靶向结肠定位效果。

Objective To evaluate the pharmacokinetics of quercetin of anti-cancer factor on colon-targeting coating dropping pills in rabbit model in vivo. Methods Totally six rabbits were randomly divided into two groups:test preparation group and reference preparation group. Rabbits in test preparation group were ig administered with anti-cancer factor colon-targeting coating dropping pills, and rabbits in reference preparation group were ig administered with core of dropping pills, each group with a single dose of 120 pills (1.5 mg curcumin per pill). Blood was taken from the carotid artery at different time after administration. A high performance liquid chromatography (HPLC) method was established for detection of curcumin in plasma for further verification of methodology. The blood concentration of curcumin at different time points was determined, and the time curve was drawn. The main pharmacokinetic parameters were calculated by DAS 2.1 software, and the relative availability (Fr) of the test preparations was calculated according to the pharmacokinetic parameters. Results The established HPLC method meets the detection requirements. The drug time curve showed that the reference preparation conformed to the double chamber model and had no lag time, but the test preparation conformed to the one room model and had the lag time. The pharmacokinetic parameters showed that, compared with reference preparation, the area under the curve (AUC_0-^∞) of test preparation increased significantly (P < 0.05), and the delay time (T_lag) prolonged significantly (P < 0.05), which was 5.307 h. Moreover, there was a significance difference between the time to peak (T_max) of reference preparation and test preparation (P < 0.05), which is 3 h and 16 h respectively. The Fr of test preparation was 74%, and its C_max was 62.6% of that of reference preparation, and no bioequivalence was found between the two. Conclusion Anti-cancer factor on colon-targeting coating dropping pills possess typical slow and controlled releasing characteristic. The accumulation of curcumin in the colon segment has good colon-targeting effect. Thereby improving the efficacy, reduce toxicity, with a good targeting colon positioning effect.

黑龙江中医药大学博士创新基金项目（B201006）；黑龙江中医药大学优秀青年教师科技创新人才支持计划（051241）