拉诺康唑原料药及其乳膏的制备与质量控制

发布时间：2018-04-29 08:38

本文选题：拉诺康唑 + 原料药　；参考：《苏州大学》2014年硕士论文

【摘要】：浅部真菌感染为一种传染性强的常见病和多发病。近年来，随着致病真菌对抗真菌药物的耐药性日趋严重，研发新的抗真菌药物，可缓解目前市售抗真菌药的抗药性。在中国，拉诺康唑原料药及其乳膏均未上市。本课题旨在研究开发一种疗效更好、抗药性低、不良反应少、使用更方便的抗真菌乳膏制剂。本课题主要进行了以下研究工作：开发拉诺康唑原料合成路线，并进行结构确证。采用自制的拉诺康唑原料药，选择较常用的油相及水相基质，对乳膏的性状、手感、含量、酸度、耐冷及耐热性等指标进行考察，确定合理的处方，开发出具有粒度小、分布均匀、细腻、涂布性好、稳定性好、不易发生油水分离以及适合工业化生产等优点的拉诺康唑乳膏制备工艺。结合拉诺康唑的药物特性和乳膏的质量要求，建立了拉诺康唑乳膏的质量标准，，包括性状、鉴别、装量、粒度、微生物限度、有关物质及含量测定等全面的质控项目。根据建立的质量标准，对拉诺康唑乳膏分别进行了光照、高温和高湿等影响因素和加速试验、长期留样试验的考察，在此基础上为拉诺康唑乳膏选择包装材料、贮存条件提供依据并预测有效期。采用自制的拉诺康唑乳膏进行了皮肤刺激性和过敏性试验，结果表明拉诺康唑软膏对家兔皮肤无明显刺激性，对豚鼠皮肤未见明显过敏反应。综上，本文对拉诺康唑原料合成路线、乳膏的制备工艺、质量标准、制剂的稳定性及其皮肤刺激性和过敏性等进行了研究，其制备工艺科学、质控项目全面，为以后生产出售奠定了坚实的基础。
[Abstract]:Superficial fungal infection is a common and frequent infectious disease. In recent years, with the drug resistance of pathogenic fungi becoming more and more serious, the development of new antifungal drugs can alleviate the current market antifungal drug resistance. In China, ranokonazole raw materials and cream are not on the market. The purpose of this study was to develop a more effective, less resistant, less adverse reaction and more convenient antifungal cream. The main work of this thesis is as follows: The synthetic route of raw materials of ranokonazole was developed and the structure was confirmed. The properties, feel, content, acidity, cold resistance and heat resistance of the cream were investigated by using the self-made ranokonazole raw material and the common oil and water phase matrix. The reasonable prescription was determined and the particle size was small. The preparation process of ranokonazole cream was characterized by uniform distribution, fine distribution, good coating property, good stability, easy oil and water separation and suitable for industrial production. Combined with the drug characteristics of ranokonazole and the quality requirements of cream, the quality standard of ranokonazole cream was established, including the quality control items such as character, identification, loading quantity, particle size, microbial limit, related substances and content determination. According to the established quality standard, the effects of light, high temperature and high humidity on the ranokonazole cream and the accelerated test were investigated, and the long-term sample retention test was carried out. On this basis, the packing materials were selected for the ranokonazole cream. The storage conditions provide the basis and predict the validity period. The skin irritation and anaphylaxis test were carried out with the self-made ranokonazole cream. The results showed that there was no obvious irritation to rabbit skin and no obvious allergic reaction to guinea pig skin. In this paper, the synthetic route of ranokonazole raw material, preparation technology, quality standard, stability, skin irritability and allergenicity of the preparation were studied. The preparation process was scientific and the quality control items were comprehensive. For the future production and sales laid a solid foundation.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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