硝酸益康唑脂质体凝胶剂的研究

【作者】 吴翠栓；

【导师】 邓意辉； 郑俊民； 郝劲松；

【作者基本信息】 沈阳药科大学 ， 药剂， 2001， 硕士

【摘要】 考察了硝酸益康唑的基本理化性质，通过正交设计筛选硝酸益康唑脂质体的处方；用微型柱离心法和超速离心法测定药物包封率，分析脂质体中硝酸益康唑的分布状态。 建立了一种测定皮肤表皮和真皮中药物含量的高效液相色谱法，用立式扩散池考察基质对脂质体释药性的影响和pH、脂质体的粒径、乙醇的含量、磷脂类型、基质对用药24小时后硝酸益康唑在皮肤表皮和真皮中含量的影响，并分别与市售软膏作了比较。结果表明，HPMC对脂质体的释药性影响小，释药速度快；脂质体溶液的pH、乙醇的含量、磷脂和基质类型对药物在表皮和真皮中的滞留量有显著性影响；以HPMC为基质的脂质体凝胶剂比市售软膏的释药速度大，药物在表皮和真皮中滞留量高。 研究了硝酸益康唑脂质体凝胶剂在体皮肤用药3天后的表皮和真皮中药物消除过程，求出消除过程中的AUC值，并与市售软膏作了比较。结果表明脂质体凝胶剂表皮和真皮中最大药物浓度大大高于市售软膏的最大药物浓度：表皮中AUC_{脂质体凝胶剂}/AUC_市售软膏为4.87，而真皮中AUC_{脂质体凝胶剂}/AUC_市售软膏为1.30，脂质体凝胶剂能显著提高药物在表皮中的滞留时间，不能增加在真皮中滞留时间，因此硝酸益康唑脂质体凝胶剂比较适合用于治疗病灶在表皮的皮肤真菌感染。 考察了硝酸益康唑脂质体的理化性质、稳定性、皮肤刺激性和初步临床疗效。电镜扫描观察、偏光显微镜观察、X衍射证明硝酸益康唑脂质体凝胶剂中无药物结晶，市售软膏中有大量药物结晶。制备的硝酸益康唑脂质体凝胶剂稳定性好，皮肤刺激性小，具有显著的临床疗效。更多还原

【Abstract】 The basic physical-phemical properties of Econazole Nitrate were studied and the formulation was optimized by orthogonal design. The two different entrapment efficiencies were determined by mincolumn centrifugation method and ultraceritrifugation method, which demonstrated the distribution of Econazole Nitrate in 1 ipo some. A high-performance liquid chromatographic method for the quantitative determination of Econazole nitrate in epidermis and dermis was developed. The effects of the additives on the drug release from liposomal gel and the effects of pH, liposome size, ethanol content, phospholipid sorts and the additives on the content of drug in epidermis and dermis 24 hours after application were studied, which were compared with the ointment on sale. The results showed that pH, ethanol content, phospholipid sorts and the additives had significant effects on the content of drug in epidermis and dermis and HPMCiposome gel had a higher rate of drug release and a more content of Econazole nitrate in epidermis and dermis than other liposomal gels ,furthermore, much higher than the ointment on sale The clearance procedures of Econazole nitrate in rat back skin (epidermis and dermis) 3 days after application were studied and AUC were calculated by trapezoidal rule, which were compared with the marketed Econazole nitrate ointment. The results showed that the C of Econazole nitrate from the prepared liposomal gel in epidermis and dermis 3 days after application were significantly higher than that from the ointment on sale. The ratios of AUCLP. to AUC0. in epidermis and dermis were 4.87 and 1.30 respectively, which showed that liposomal gel could prolong duration time of Econazole nitrate in epidermis but not in dermis. It demonstrated Econazole nitrate liposomal gel was adapted to fungal skin infections whose focus is in epidermis. The physical-phemical properties, stability, skin irritation and preliminary clinical pharmacological action of prepared liposomal gel were investigated. The results of polarizing microscope observation scanning microscope observation and X-way diffraction test showed a lot of crystal of Econazole nitrate in the ointment on sale ,but no crystal in prepared liposomal gel. The irritation test and preliminary clinical investigation showed the prepared liposomal gel had no irritation for application and had significant pharmacological action for fungal skin infections.更多还原