【作者】 余李敏；

【导师】 李三鸣；

【作者基本信息】 沈阳药科大学 ， 药剂学， 2006， 硕士

【摘要】 离子交换纤维具有“储库”性质和解离平衡特点，可以作为新型的药物载体。本文将药物结合在纤维上，然后均匀分散在凝胶基质中制备药物纤维凝胶体系，并与普通凝胶对比考察了体外释放和体外渗透情况；同时研究了离子导入对其体外渗透情况影响，并进行了大鼠体内药动学研究对自行设计的模型的合理性进行最终的评价。 本论文以强碱性阴离子交换纤维(ZB-2)为体系，研究了纤维的一些基本性质：纤维的湿真密度为0.28g／ml，湿视密度为0.23g／ml，比表面积为1.40×10~4m~2／g，全交换容量为3.1mmol／g，pKa为8.3，溶胀度为10％～30％。本文选用非甾体抗炎药酮洛芬为模型药物，研究中几个重要性质参数结果为：37℃条件下在水，生理盐水和PBS(pH7.4)中的平衡溶解度分别为176.1±7.2，184.7±2.8和2871.0±103.4μg／ml；KP在正辛醇／水、正辛醇／生理盐水和正辛醇／pH7.4PBS体系中的表观油水分配系数的对数值分别为2.31、2.26和0.87；同时建立紫外分光光度法用于药物和纤维的相互作用研究中药物含量的测定，建立高效液相色谱法用于对凝胶体系进行研究中KP的含量测定。 分别采用静态法与动态法制备药物纤维，并考察了其释药情况，结果表明：该离子交换反应为放热反应；静态交换中粒径越小，药物溶液浓度越高，则反应越快越完全，温度越高，反应越快但是交换量降低；动态法中随着纤维粒径的增加，溶液浓度的加大，流速的加快，反应温度的升高，穿透点提前；通过固液接触角，显微照片，差示扫描热分析图谱和红外光谱研究药物纤维结合机理，结果表明药物是以离子键的形式结合在纤维上的；药物纤维的释药过程是药物纤维结合的逆过程，研究结果表明都符合一级动力学方程，影响因素与结合过程相似。 设计正交实验确定了普通凝胶的最佳处方，在此基础上加入药物纤维制备药物纤维凝胶，以0.22μm微孔滤膜进行体外释放实验，考察了纤维和外加离子的影响，结果表明纤维能够降低因药物浓度的变化引起的释药变化的波动程度，起到了控制释药速率波动的缓冲剂的作用，但同时使释药速率降低。外加离子能够促进药物的释放，离子提供层是促进药物释放的有效方式。对药物纤维凝胶的体外释药过程进行拟合，结果符合Higuchi模型。 体外经皮渗透实验表明：纤维能够控制药物经皮渗透速率，离子提供层能提高药物的体更多还原

【Abstract】 Ion-exchange fibers as a new kind of drug carrier could be used for drug delivery system by the ion exchange equilibrium between drug ions and surrounding counter ions. In this paper, drug-fibers complex was prepared and added to gel, and the drug-fibers gel was harvested as a uniform system. The release studies and permeation studies of the products were carried on compared with simple gel, and the iontophoresis effects were also studied during permeation studies and the pharmacokinetics in rats which were carried out eventually for the ultimate rationality of the self-designed model.The ion-exchange fibers studied were strong anion-exchanger material (ZB-2).Several basic properties of the fibers such as true wet density, apparent wet density, specific surface, total ion-exchange capacity, pKa and inflation extent were determined as 0.28 g/ml, 0.23 g/ml, 1.40×10~4 m~2/g, 3.1 mmol/g, 8.3 and 10%～30% respepectively. Ketoprofen, KP, used as a model drug in the paper, is a nonsteroidal anti-inflammatory (NSAIDs) with analgesic and antipyretic actions. Several important parameters of KP were studied at 37℃ as follows: The solubility of KP in water, saline and pH 7.4 PBS were 176.1±7.2, 184.7±2.8 and 2871.0±103.4 μg/ml respectively and the corresponding logarithm of apparent partition coefficients using octanol as oil phase were 2.31、2.26 and 0.87 respectively. Two methods, UV spectrophotometry and HPLC, were developed for studies of ion exchange interaction or equilibrium in vitro and the studies for gel in vitro or in vivo respectively.Drug-fibers complex was prepared by bath method or column method, and it was proved that the exchange reaction between KP and fibers was not facilitated by energy. The factors affecting loading of drug were explored as follows: higher loading amount as a result of the smaller fiber size, the lower of reaction temperature and the higher concentration of KP solution for bath method; the breakthrough point was advanced by bigger fiber size, higher concentration, higher flow rate and higher reaction temperature for column method; The combination mechanism of KP-fibers was investigated by contact angle, microgram, DSC and IR spectrum method, and it更多还原