摘要
测定聚酰胺-胺PAMAM树状聚合物对灯盏花素的增溶性能并探讨其增溶机制;研究PAMAM树状聚合物对灯盏花素体内药代动力学的影响。测定和比较了G1、G1.5、G2、G2.5代PAMAM在不同浓度和不同pH时对灯盏花素的增溶量;另将12只大鼠随机均分为2组,每组6只,分别以灯盏花素及灯盏花素-PAMAM灌胃,采用反相高效液相色谱法检测血浆药物浓度。在pH小于7.0时,PAMAM树状聚合物对灯盏花素的增溶量随着PAMAM代数、浓度和溶液pH的增加而增大,其增溶机制为灯盏花素的羧基与PAMAM的伯胺和叔胺发生静电作用;灯盏花素、灯盏花素-PAMAM口服给药的Cmax分别为(119.65±9.36)和(518.17±17.07)ng·mL-1,AUC0-8h分别为(370.09±63.08)和(1219.47±201.87)ng·h·mL-1,两者具有极显著性差异(P<0.01)。说明PAMAM能显著提高灯盏花素在水中的溶解度;大大改善灯盏花素口服给药的生物利用度。
To study the solubilization of breviscapine with polyamidoamine （PAMAM） dendrimers and probe the solubilizing mechanism and investigate the influence of PAMAM dendrimers on the pharmacokinetics of breviscapine, the solubilization of breviscapine by PAMAM dendrimers of generations GI, G1.5, G2 and G2.5 with different concentrations were determined and compared in different pH conditions. Twelve rats randomized into 2 groups were separately orally administered breviscapine and breviscapine combining with PAMAM. Drug in plasma was extracted and determined with HPLC. In pH condition lower than 7.0, the solubilization of breviscapine by PAMAM dendrimers enhanced as the generation and concentration of PAMAM dendrimers as well as the pH increased. Its solubilizing mechanism involves an electrostatic interaction between the carboxyl group of breviscapine and the primary amines and tertiary amines of PAMAM dendrimers. The pharmacokinetics parameters Cmax and AUC0-8h of breviscapine were （119.65 ± 9.36） ng·mL^-1 and （370.09 ± 63.08） ng·h·mL^-1. For breviscapine combined with PAMAM dendrimers, the Cmax and AUC0-8 h were （518.17 ± 17.07） ng·mL^-1 and （1 219.47 ± 201.87） ng·h·mL^-1, respectively. There were significant differences of AUC0-8 h between breviscapine and breviscapine combined with PAMAM dendrimers （P 〈 0.01）. PAMAM dendrimers can greatly increase the solubility of breviscapine in water and can improve the oral bioavailability of breviscapine significantly.
出处
《药学学报》
CAS
CSCD
北大核心
2009年第2期197-202,共6页
Acta Pharmaceutica Sinica
基金
国家中医药管理局中医药科学技术研究专项(06-07ZP21)
