鼻腔灌流法比较葛根素及其衍生物透鼻黏膜吸收差异  

The nasal perfusion method to compare the nasal mucosa absorption between puerarin and its derivatives

作　　者：马金秋 宋兴爽 李祺 欧歌 王椿清 张首国 杜丽娜 MA Jinqiu;SONG Xingshuang;LI Qi;OU Ge;WANG Chunqing;ZHANG Shouguo;DU Lina(Beijing Institute of Radiation Medicine,Beijing 100850,China;Pharmacy College,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]军事科学院军事医学研究院辐射医学研究所,北京100850 [2]山东中医药大学药学院,山东济南250355

出　　处：《沈阳药科大学学报》2023年第8期994-999,共6页Journal of Shenyang Pharmaceutical University

基　　金：北京市自然科学基金面上项目(7202147)。

摘　　要：目的采用鼻腔灌流考察葛根素及其水溶性、脂溶性两种衍生物的透鼻黏膜吸收能力,探讨药物透鼻黏膜吸收效率与其分子量、溶解性等不同性质之间的关系。方法SD雄性大鼠麻醉后安装鼻腔灌流循环系统,取7 mL鼻腔灌流液加入循环系统,按预定时间点取样,采用高效液相色谱法测定葛根素及其水溶性、脂溶性两种衍生物的各时间点样品浓度,计算吸收速率常数,判断各化合物透鼻黏膜效率。结果葛根素、3′-(二甲基氨基)甲基葛根素盐酸盐浓度、7-O-(6-溴己基)-葛根素的线性范围分别为17.0~170.0μg·mL^(-1)、5.0~200.0μg·mL^(-1)、5.1~202.0μg·mL^(-1);三者透鼻黏膜吸收速率常数分别为(7.10±1.15)×10^(-3)、(6.83±0.55)×10^(-3)、(6.76±1.66)×10^(-3),K(葛根素)>K[3′-(二甲基氨基)甲基葛根素盐酸盐]>K[7-O-(6-溴己基)-葛根素],葛根素透鼻黏膜效率最高。结论透鼻黏膜吸收效率可能和分子量有关,分子量较小可能更有利于透黏膜吸收,同时过度亲水或亲脂的药物可能都不利于透黏膜吸收。因此葛根素鼻用制剂有希望成为临床应用新选择。Objective To investigate the nasal mucosal permeability of puerarin and its two derivatives,by using nasal parfusion and To evaluate the relationship between the transmucosa permeability and the physicochemical characteristics of drugs,such as molecular weight and solubility.Methods The linear range of puerarin,3′-(dimethylamino)methyl puerarin and 7-O-(6-bromohexyl)-puerarin methanol solution was determined by HPLC.SD male rats were anesthetized and placed in the nasal perfusion circulation system.Nasal perfusion fluid of 7 mL was added into the circulatory system and the samples were withdrawn at the predetermined time points.The residual drug concentration ρ_(n) at each time was determined by HPLC and the transmucosa absorption rate constant K was calculated.Results The concentration linear range of puerarin,3′-(dimethylamino)methyl puerarin hydrochlorid,and 7-O-(6-bromohexyl)-puerarin was 17.0-170.0μg·mL^(-1),5.0-200.0μg·mL^(-1)and 5.1-202.0μg·mL^(-1),respectively.The higher the drug absorption constant K,the better the nasal mucosal permeability,K(Puerarin)K[3′-(Dimethylamino)methyl puerarin hydrochloride]K[7-O-(6-bromohexyl)-puerarin],which indicated puerarin had the best transmucosa ability.Conclusion The transmucaosa ability may be related closely with molecular weight.Low molecular weight may be more advantageous for transmucosa permeability.Very hydrophilic or hydrophobic drugs may be not feasible for transmucosa absorption.Therefore,nasal puerarin formulations could be a novel choice for clinical application.

关 键 词：鼻黏膜 鼻腔灌流 葛根素 透黏膜吸收 

分 类 号：R96[医药卫生—药理学]