天麻素经鼻给药吸收特性的研究

Study of Nasal Absorption Characteristics of Gastrodin

目的考察天麻素的离体、在体经鼻吸收特性,为天麻素经鼻给药制剂的研究提供依据。方法采用改良Franz扩散池法,选用新鲜的家猪鼻黏膜作为渗透屏障,以黏膜渗透系数为指标,评价天麻素离体鼻黏膜吸收特性;采用鼻腔循环灌流法,以含天麻素的生理盐水为鼻腔循环液,HPLC测定天麻素含量,考察天麻素在体大鼠鼻黏膜吸收特性。结果天麻素低、中、高剂量组的离体猪鼻黏膜渗透系数分别为1.9×10^(-3),1.3×10^(-3),4.3×10^(-3) cm^(-2)·min^(-1);大鼠在体吸收速度常数分别为2.9×10^(-3),6.0×10^(-3),2.4×10^(-3) min-1。天麻素的黏膜吸收量随其浓度的增加而增加,但其吸收速度常数较小,且在体实验所选择的中浓度天麻素的鼻黏膜吸收速度常数要大于低浓度和高浓度。结论天麻素可经鼻吸收,但其在体吸收速度与黏膜渗透系数都较小,在制备其鼻腔给药制剂时,需要通过增加促渗剂或改变剂型等方法以增加鼻黏膜吸收。

OBJECTIVE To investigate in vitro and in vivo nasal absorption characteristics of gastrodin, so as to provide the basis for the study of gastrodin nasal preparation. METHODS In vitro nasal absorption characteristics of gastrodin was evaluated by using Franz diffusion cell with fresh pig nasal mucosa as permeation barrier and mucosal permeation coefficient as index. In rat nasal circulatory perfusion experiment, using medicated normal saline for nasal liquid circulation, the content of gastrodin was determined by HPLC to investigate the in vivo nasal absorption characteristics. RESULTS Mucosal permeation coefficient in vitro of fresh pig nasal were respectively 1.9×10^-3, 1.3×10^-3, 4.3×10^-3 cm^-2·min^-1 in gastrodin group with low dose, middle dose and high dose; Absorption rate constants in rat nasal circulatory perfusion experiment were respectively 2.9×10^-3, 6.0×10^-3, 2.4×10^-3 min^-1. Mucosal absorption amount of gastrodin were increased with increasing drug concentration, but the absorption rate constant was small, and mucosal absorption amount of gastrodin group with middle concentration was better than low concentration and high concentration. CONCLUSION Although gastrodin can be absorbed through nasal mucosa, its absorption rate constant and mucosal permeation coefficient are small, which means that it is needed to increase the absorption of nasal mucosa by increasing the osmotic agent or changing the dosage form in the preparation of gastrodin nasal administration.