环糊精及其衍生物对磷酸川芎嗪鼻黏膜吸收的促进作用  

Effect of cyclodextrins on the intranasal absorption of tetramethylpyrazine phosphate

作　　者：梅丹[1] 毛世瑞[1] 钱频非[2] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]东南大学医院,江苏南京210018

出　　处：《沈阳药科大学学报》2008年第12期933-938,共6页Journal of Shenyang Pharmaceutical University

摘　　要：目的研究环糊精及其衍生物对磷酸川芎嗪大鼠鼻黏膜吸收的影响。方法采用大鼠在体鼻循环法研究环糊精的浓度和种类对磷酸川芎嗪鼻黏膜吸收的促进作用，计算磷酸川芎嗪体外吸收速度常数；通过体内法研究大鼠鼻黏膜给药后药物在体内的药物动力学参数，并计算绝对生物利用度。在此基础上就在体法与体内法两种方法的相关性进行考察。结果羟丙基-β-环糊精（hydroxypropy-β-cyclodextrin，HP-β-CD）可显著促进磷酸川芎嗪的鼻黏膜吸收。但在质量分数为0．5％～5．0％内，HP-β-CD的吸收促进作用无显著差异（P〉0．05）。和β-环糊精（β-cyclodextrin，β-CD）相比，HP-β-CD的吸收促进作用显著增强。对照组、质量分数为0．5％β-CD和质量分数为0．596HP-β-CD组磷酸川芎嗪鼻黏膜吸收速度常数（ka）分别为0．158、0．163、0．233mg·min^-1，对照组与HP-β-CD组有显著性差异（P〈0．05），但和β-CD组无显著差异（P〉0．05）。对照组与HP-β-CD组的药-时曲线均符合二室模型，绝对生物利用度分别为45．7％和66．596，两组间绝对生物利用度有显著性差异（P〈0．05）。结论HP-β-CD能显著提高磷酸川芎嗪大鼠鼻黏膜吸收速度和生物利用度。大鼠在体鼻循环法与体内实验结果相关性良好。Objective To assess the absorption promoting effect of cyclodextrins on the intranasal absorption of tetramethylpyrazine phosphate（TMPP）. Methods An in situ nasal recirculation method was used to study the effect of cyclodextrin concentration and type on the intranasal absorption of TMPP. The absorption rate constants were calculated. In vivo studies were carried out in rats and the pharmacokinetic parameters and absolute bioavailability were evaluated, after that the correlation between in vitro and in situ methods for TMPP intranasal absorption was investigated. Results Hydroxypropyl-β-cyclodextrin（HP-β- CD）could enhance the intranasal absorption of TMPP significantly. However, no remarkable difference in absorption was found in HP-β-CD con6entration range of 0.5 % - 5.0 % （P 〈 0.05）. The absorption enhancing effect of HP-β-CD was stronger than that of β-CD. The in vitro absorption rate constants （ka） were 0. 158,0. 163, 0. 233 mg· min^- 1 for the control group, 0.5 % β-CD group and 0.5 % HP-β-CD group, respectively. A considerable difference was found between the control group and the 0.5 % HP-β-CD group （P 〈 0.05）. However, no statistical difference was found between the control group and 0.5 % β-CD group （P 〉 0.05）. The in vivo plasma concentration-time profiles of the control group and HP-β-CD group can be described with a two-compartment model and their absolute bioavailability were 45.7 % and 66.5 %, respectively, with significant differences between the control group and HP-β-CD group（P 〈 0.05）. Conclusions HP-β-CD is a good intranasal absorption enhancer for TMPP. A good exponential correlation between TMPP plasma concentration in vivo and TMPP absorption amounts in vitro was established.

关 键 词：鼻黏膜 磷酸川芎嗪 羟丙基-Β-环糊精 Β-环糊精 

分 类 号：R94[医药卫生—药剂学]