三七总皂苷鼻用凝胶喷雾剂的药动学与药效学研究  

Pharmacokinetic and pharmacodynamic study of Panax notoginseng saponins nasal gel spray

作　　者：邓春丽[1] 罗洁琦[1] 沙先谊[1] 方晓玲[1] 

机构地区：[1]复旦大学药学院药剂学教研室,上海201203

出　　处：《中国临床药学杂志》2014年第5期276-282,共7页Chinese Journal of Clinical Pharmacy

基　　金：国家重大科技专项经费资助项目(编号2009ZX09310-006);上海市科学技术委员会科研计划项目(编号10DZ1972400)

摘　　要：目的研究自制三七总皂苷鼻用凝胶喷雾剂的生理适应性、家兔给药后体内的药动学过程,及其对心血管疾病的保护作用。方法选用扫描电镜法,考察喷雾剂的鼻纤毛毒性;HPLC法测定三七总皂苷鼻用凝胶喷雾剂家兔鼻腔给药后血样中人参皂苷Rb1、Rg1的浓度,考察药物在体内的动力学过程,并计算药动学参数;建立大鼠急性缺血性心肌梗死模型,考察三七总皂苷鼻用凝胶喷雾剂对心脑血管疾病的保护作用。结果三七总皂苷鼻用凝胶喷雾剂给药后,Rb1、Rg1在家兔体内的过程符合二室模型,其绝对生物利用度比三七总皂苷滴鼻液高,分别为(42.31±7.54)%和(81.06±32.71)%;可大幅减少大鼠左冠状动脉闭塞所致的心肌梗死面积,且呈剂量依赖性,剂量越高,保护作用越强;该喷雾剂基本无明显鼻纤毛毒性。结论药动学、药效学及鼻纤毛毒性试验结果证明,三七总皂苷鼻腔给药制剂具有很好的开发前景。AIM To prepare a nasal spray with gelling agent for intranasal delivery of Panax notoginseng saponins（PNS）, to investigate its absorption rate and pharmacokinetic profile with different routes of administration and formulations, and to evaluate its efficacy on a myocardial infarction model in rabbits. METHODS The ciliotoxicity from the gel were investigated. Concentration of Rbl or Rgl was determined using a simple HPLC method. The pharmacokinetic parameters and cardio-protective effect against myocardial infarction of the gel were investigated. RESULTS The in vivo course of Rbl or Rgl in rabbits conformed to two-compartment model after intranasal administration of PNS gel and the absolute bioavailability was higher than that of PNS intranasal solution [ （42.31 ± 7.54） % vs （ 81.06 ± 32. 71） % ]. The gel significantly reduced myocardial infarct size induced by occlusion of the left coronary artery. And the effects were dose-dependent, the higher dose, the better effects. The spray was no obvious ciliotoxicity. CONCLUSION PNS nasal spray with gelling agent may be a promising approach for the intranasal delivery of PNS for prolongation of drug delivery and improvement of systemic Rb1 and Rg1 absorption, thus enhancing its bioavailability and cardio-protective effect.

关 键 词：三七总皂苷 鼻腔给药 药动学 药效学 凝胶 

分 类 号：R285.5[医药卫生—中药学]