目的 評價克癌素結(jié)腸定位包衣滴丸有效成分姜黃素在家兔體內(nèi)的藥動學(xué)。方法 6只家兔隨機等分成兩組：受試制劑和參比制劑組，受試制劑組給予克癌素結(jié)腸定位包衣滴丸，參比制劑組給予滴丸丸芯，兩組均按單劑量ig給藥120丸（每丸含姜黃素1.5 mg），于給藥后不同時間頸動脈取血。建立血漿中姜黃素檢測的高效液相色譜（HPLC）法，并進(jìn)行方法學(xué)驗證；測定各時間點家兔體內(nèi)姜黃素血藥濃度，繪制藥時曲線，DAS 2.1軟件計算主要藥動學(xué)參數(shù)，根據(jù)藥動學(xué)參數(shù)計算受試制劑的相對利用度（Fr）。結(jié)果 建立的HPLC法的方法學(xué)試驗均符合檢測要求；藥時曲線顯示，參比制劑丸芯符合雙室模型，無滯后時間，而受試制劑符合一室模型，有滯后時間；藥動學(xué)參數(shù)顯示，與參比制劑比較，受試制劑的統(tǒng)計矩參數(shù)藥時曲線下面積（AUC_0-^∞）顯著增大、延遲時間（t_lag）為5.307 h，顯著延長（P < 0.05），參比制劑的達(dá)峰時間（t_max）為3 h，受試制劑t_max為16 h，兩組差異顯著（P < 0.05）。受試制劑的Fr為74.0%，其C_max為參比制劑的62.6%，二者間均不具生物等效性。結(jié)論 克癌素結(jié)腸定位包衣滴丸具有典型的緩（控）釋特征，姜黃素成分結(jié)腸段蓄積，具有良好的靶向結(jié)腸定位效果。

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.

黑龍江中醫(yī)藥大學(xué)博士創(chuàng)新基金項目（B201006）；黑龍江中醫(yī)藥大學(xué)優(yōu)秀青年教師科技創(chuàng)新人才支持計劃（051241）