王思玲,伊滕吉将,李乐道,苏德森,顾学裘
WANG Si ling 1; ITO Ji jiang 2; LI Le dao 1; SU De sen 1; Gu Xue qiu 1 (1. School of Pharmacy;

• 1:沈阳药科大学药学院
• 2:日本近畿大学
• 3:沈阳药科大学药学院
• 4:沈阳药科大学药学院

摘要(Abstract)：

目的制备以羟丙基 β环糊精为传递系统的双硫伦眼用制剂。通过药物环糊精包合物的形成 ,改善双硫伦的溶解性、眼角膜透过性及生物利用度。方法采用饱和溶液法制备双硫伦 羟丙基β环糊精包合物。以离体与在体兔眼角膜透过实验 ,通过对眼房水中透过药量的监测及对透过累积数据的药物动力学方程模拟 ,求出透过参数与生物利用度。结果将 0 1 %双硫伦 羟丙基 β环糊精包合物制剂与 0 2 5 %双硫伦 羟丙基β环糊精包合物分别经眼给予家兔2 0 μL/kg后 ,于家兔眼房水中检测到理想药物浓度 ,峰浓度分别为 ( 1 2± 2 4 ) μmol/L与 ( 4 4± 5 1 ) μmol/L ,相应的达峰时间为 4 0min与 2 0min。对渗透累积数据进行药物动力学方程模型并计算渗透常数 ,在体与离体实验有着良好的相关性 ,高剂量组生物利用度 (AUC)为低剂量组的 2 5倍 ,吸收速率常数 (Ka)与渗透系数 (Kp)皆为低剂量组的 3倍。 结论药物环糊精包合物的形成大大提高了制剂中双硫伦的溶解度、眼角膜透过性与生物利用度 ,羟丙基β环糊精是一个有效的眼用药物传递系统。
Objective The objective of the study is to test a kind of eye drops containing a high concentration of DSF in a cyclodextrin based drug delivery system. This system increased DSF solubility in eye drops, permeability into the eye and availability.Methods The drug cyclodextrin inclusion complexes solution was prepared by the saturated solution method. In vitro and in vivo penetration through cornea was investigated by measuring DSF concentration from humor samples. Permeability parameters and availability were estimated by applying a physiologically based pharmacokinetic model to the profile of the drug concentration versus time.Results The resultant drug concentration was measured from humon samples after 0 1% DSF and 0 25% DSF inclusion complexes eye drops were instilled to the rabbit′s cornea, respectively. The profiles of the drug content versus time reached the peak concentration of (12±2 4)μmol/L and (44±5 1)μmol/L and 2 times of the peak time were 40 min and 20 min . Permeability parameters were correlated well with those obtained from the in vivo experiments, higher permeability constants were obtained in the 0 25% DSF preparation compared with that in 0.1% DSF, a 2 5 fold higher in area under the curve, a 3 fold greater in absorption and transcorneal constants.Conclusions The formulation of the drug cyclodextrin complex enhanced greatly the solubility of DSF in eye drops, the permeability into the eye and its availability. This meant that HPβCD was an effective ophthalmic drug delivery system.

关键词(KeyWords)： 双硫伦;二乙二硫氨甲酸;羟丙基β环糊精;包合物;角膜透过性
disulfiram; diethyldithiocarbamic acid; α hydroxypropyl β cyclodextrin; inclusion; transcorneal penetration

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 王思玲,伊滕吉将,李乐道,苏德森,顾学裘
WANG Si ling 1; ITO Ji jiang 2; LI Le dao 1; SU De sen 1; Gu Xue qiu 1 (1. School of Pharmacy;

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