姜黄素-羧甲基壳聚糖偶联物对环孢素A肠吸收的影响

目的:探讨姜黄素-羧甲基壳聚糖偶联物对环孢素肠吸收的影响,为其临床应用提供理论基础。方法:采用大鼠在体单向肠灌流实验,用HPLC测定灌流液中环孢素的含量,计算不同浓度的姜黄素(Cur)、羧甲基壳聚糖(CMCS)、CMCS-Cur(CC)、CMCS-EDA-Cur(CEC)对环孢素在十二指肠和空肠的表观吸收速率常数(Ka)和肠壁有效通透性系数(Peff)的影响。结果:在十二指肠和空肠部位,加入Cur、CMCS、CC、CEC的实验组环孢素的Ka和Peff值高于单纯环孢素组(P<0.05);0.1%CsA&CMCS组高于0.1%CsA&Cur组(P<0.05);0.1%CEC&CsA组Ka、Peff值高于0.01%和1%CEC&CsA(P<0.05)。结论:Cur、CMCS、CC、CEC均能促进CsA在十二指肠和空肠部位的吸收,相同浓度下CMCS的促环孢素吸收作用优于Cur。

Effects of curcumin-carboxymethyl chitosan conjugates on intestinal absorption of cyclosporin A

OBJECTIVE To study the effects of curcumin-carboxymethyl chitosan conjugates on intestinal absorption of cyclosporin A,provide a theoretical foundation for their clinical applications.METHODS Single pass intestinal perfusion in situ was used to study the effects of curcumin-carboxymethyl chitosan conjugates on intestinal absorption of cyclosporin A.High performance liquid chromatography was used to determine cyclosporin A content,and the effects of different concentrations of Cur,CMCS,CMCS-Cur (CC) and CMCS-EDA-Cur (CEC) on the absorption rate constant (Ka) and intestinal effective permeability coefficient (Peff) of cyclosporin A in duodenum and jejunum.RESULTS The Ka and Peff values of experimental groups administering cyclosporine A containing Cur,CMCS,CC or CEC in duodenum and jejunum were higher than those of pure cyclosporin A group (P<0.05).The Ka and Peff values of 0.1% CsA&CMCS group were higher than those in 0.1%CsA&Cur group (P<0.05),and Ka and Peff values of 0.1% CEC&CsA group were higher than those in 0.01% and 1% CEC&CsA groups (P<0.05).CONCLUSION Cur,CMCS,CC and CEC can promote absorption of cylosporin A in duodenum and jejunum.At the same concentration,the promoting effects of CMCS are superior to those of Cur on absorption of cylosporin A.