异亚丙基莽草酸脂质体体外评价及鼻腔给药后药物动力学研究  

In Vitro Quality Evaluation and Pharmacokinetics after Nasal Administration of Isopropylidene Shikimic Acid Liposomes

作　　者：曲昌海[1] 张晓燕[2] 杨培[1] 付京[1] 张慧[1] 田晶辰[1] 尹兴斌[1] 倪健[1] 

机构地区：[1]北京中医药大学,北京100029 [2]军事医学科学院毒物药物研究所

出　　处：《中国药师》2013年第8期1099-1102,共4页China Pharmacist

基　　金：国家自然科学基金面上项目(编号:81173563);北京中医药大学复方中药制药创新团队基金(编号:2011-CX70-13);北京中医药大学自主选题项目专项基金(编号:2011-JYBZZ-XS037)

摘　　要：目的:制备脑缺血再灌注损伤的保护药物异亚丙基莽草酸脂质体,并对其体外特性及鼻腔给药后的药物动力学进行研究,探讨鼻腔给药的可行性。方法:脂质体采用薄膜分散-探针超声法制备,采用纳米粒度分析仪对其粒径分布进行测定,包封率通过超滤法测得;选择羊鼻中膈黏膜作为模型,进行体外黏膜透过性试验;体内过程考察选择大鼠作为试验动物,通过鼻腔给药,考察其药物动力学过程。结果:在选定的处方和工艺条件下,制得的脂质体外观均匀,平均粒径约(244.1±44.7)nm,包封率为(96.83±1.04)%,制剂总含量14,68 mg·ml^(-1);体外透膜试验中,异亚丙基莽草酸脂质体4 h的透过率约90%左右;大鼠鼻腔给药后,5～10 min即达到最高血药浓度,生物利用度为92,64%。结论:异亚丙基莽草酸脂质体透膜和吸收性能良好,可以用于鼻腔途径给药。Objective： To study the characters in vitro and pharmacokinetics in rats of isopropylidene shikimic acid liposomes to e- valuate the feasibility of nasal administration of the liposoems in the treatment of cerebral ischemia reperfusion injury. Method ： The li- posomes were prepared by a film dispersion method. The size and size distribution were detected by a nanoparticle size analyzer, and the entrapment efficiency was determined using a uhrafihration method. In vitro transmembrane penetration was studied using a Franz - diffusion cell method with sheep nasal septum mucosa as the barrier. The study of pharmacokinetics was carried out in rats. Result： The in vitro characters of the liposomes were spherical, mean size of （ 244.1 ± 44.7 ） nm and entrapment efficiency of （ 96.83 ±1.04 ） % with the total drug amount of 14.68 mg · ml- 1. In the 4th h, the accumulative permeation rate was about 90%, which showed promising permeability. The results of pharmacokinetics in rats showed that the drug was absorbed rapidly, and the bioavailability was about 92.64%. Conclusion ： Isopropylidene shikimic acid liposomes are suitable for the nasal administration.

关 键 词：异亚丙基莽草酸脂质体 鼻腔给药 体外特性 药物动力学 

分 类 号：R945[医药卫生—微生物与生化药学]