【作者】 翟志慧；

【导师】 沈琦；

【作者基本信息】 上海交通大学 ， 制药工程， 2009， 硕士

【摘要】 本文研究丁香酚和冰片对P-gp底物秋水仙碱和罗丹明123在大鼠小肠的吸收和外排影响,在此基础上研究新型给药系统纳米制剂和微乳制剂对药物吸收的影响,并进行体内药动学的研究。采用扩散池试验技术,研究不同浓度的丁香酚、冰片对罗丹明123和秋水仙碱在吸收与外排方向上的影响,结果表明丁香酚和冰片在一定浓度范围内均可促进药物的肠道吸收,药物增渗倍数提高大约2-9倍。利用二元溶剂分散法制备的冰片纳米粒对罗丹明123吸收方向或外排方向的转运并没有产生明显的影响,可能与纳米粒的缓释作用有关。利用伪三元相图确定以Tween80为表面活性剂,无水乙醇为助表面活性剂,肉豆蔻异丙酯为油相,Km为3,丁香酚含量为2~4%的微乳配方,丁香酚微乳状态比非微乳状态明显促进了药物的吸收和抑制药物的外排,在吸收方向的增渗倍数为2.13,外排方向的抑制作用为0.34。在大鼠体内药动学研究中,吸收促进剂能显著增加秋水仙碱的吸收。秋水仙碱制备成含丁香酚的微乳后,2h内血药浓度较为平稳,且4h的血药浓度比其他组别高。综上所述,丁香酚和冰片作为吸收促进剂,可提高药物胃肠吸收,增强药效,为临床药物的开发提供了依据。更多还原

【Abstract】 The present study investigates the eugenol and borneol affect the absorption and secretion of colchicin and rhodamine123 by rat intestine cells through diffusion cell technology. On this basis, we probe into the novel drug deliver system nanoparitcle and microemuLsion affect the drug absorption and clarify the pharmacodynamic and pharmacokinetic parameters.Research eugenol and bornelo contribute to the drug intestine absorption by the diffusion cell method. Eugenol and borneol contribute to the drug intestine absorption. The drug permeability (rhodamine 123 and colchicin) increase 2-9 times. We prepared borneol-PLGA nanoparticle through binary solvent dispersion method. We investigate the lower concentration of borneol adjust the permeability of rhodamine 123 through intestinal mucosa by the diffusion cell method. The results showed that nanoparticle form does not affect the absorption and secretion remarkably. We screened the formulation of microemuLsion through pseudo- ternary diagram and confirm the formuLation as following: Tween80 serve as surfactant, ethanol serve as aid-surfactant, isopropyl myristate serve as oil phase, Km is 3, eugenol content is 2~4%. MicroemuLsion formulation stimulates the absorption and inhibit the secretion remarkably compared with non-microemuLsion formuLation. The absorption and secretion coefficient increase 2.13 and 0.34 times separately. The inhibition effects on secretion are more remarkable than stimuLation effects on absorption. The resuLts of pharmacodynamic and pharmacokinetic study in rat show: sorbefacient can stimulate absorption of colchicin remarkably and accelerate distribution and elimination in vivo. Colchicin microemuLsion formuLation containing eugenol acquired steady serum concentration in 2 hours and higher concentrations than other formuLations in 4 hours.The results break a new path to create new formuLation P-gp antagonist, stimuLate drug absorption in intestine and improve the curative effect.更多还原