论文部分内容阅读
目的:研究白藜芦醇衍生物[(E)-3,5,4′-三甲氧基-1,2-二苯乙烯(BTM-0512)]在大鼠肠道的吸收特性。方法:采用大鼠在体肠循环实验,考察不同的药物浓度、肠段及胆汁对吸收参数的影响。BTM-0512在大鼠肠循环液中的药物浓度采用HPLC法测定;循环液中酚红浓度采用UV法测定。结果:在肠道正常pH情况下,低、中、高3个浓度的BTM-0512的吸收速率常数(K_a)分别为0.6290,0.5329(扎胆管),0.5330(未扎胆管),0.6791 h~(-1),表明不同浓度BTM-0512在肠道的吸收速率常数相近,且胆汁对BTM-0512肠道吸收没有影响(P>0.05);在十二指肠、空肠、回肠,结肠的吸收速率常数分别为0.9492,0.5216,0.3835,0.1185 h~(-1),统计结果显示,不同肠段间吸收有明显差异(P<0.05)。结论:BTM-0512在肠道内是以被动扩散的方式被吸收,呈现一级动力学过程。因BTM-0512在整肠段均有吸收,剂型设计时可考虑肠溶制剂。
Objective: To study the intestinal absorption of resveratrol derivative [(E) -3,5,4’-trimethoxy-1,2-stilbene (BTM-0512)] in rats. Methods: The rat intestine circulation experiments were conducted to investigate the effects of different drug concentrations, intestinal segments and bile on the absorption parameters. The drug concentration of BTM-0512 in rat intestinal circulating fluid was determined by HPLC method. The concentration of phenol red in circulating fluid was determined by UV method. Results: Under the condition of normal intestinal pH, the absorption rate constants (K_a) of BTM-0512 were 0.6290,0.5329, 0.5330 (without ligating bile duct), 0.6791 h ~ ( -1), indicating that the absorption rate constants of BTM-0512 at different concentrations in the intestine are similar, and the bile has no effect on the intestinal absorption of BTM-0512 (P> 0.05); in the duodenum, jejunum, ileum, The constants were 0.9492,0.5216,0.3835,0.1185 h ~ (-1) respectively. The statistical results showed that there was a significant difference in absorption between different intestine segments (P <0.05). Conclusion: BTM-0512 is absorbed by the passive diffusion in the intestine and presents a first-order kinetic process. Due to BTM-0512 absorption in the entire bowel, dosage forms can be considered when designing enteric formulations.