盐酸吡硫醇纳米制剂的研究

发布时间：2018-01-14 19:34

本文关键词：盐酸吡硫醇纳米制剂的研究　出处：《吉林大学》2014年硕士论文　论文类型：学位论文

【摘要】：盐酸吡硫醇是维生素B6的类似物，临床上主要可以治疗老年痴呆症。现上市的产品主要包括盐酸吡硫醇片剂、盐酸吡硫醇注射剂和盐酸吡硫醇冻干粉针剂。而据临床使用者反馈，该注射剂具有一定的血管刺激性。为了降低其血管刺激性，本研究将其制备成为纳米制剂，主要制备为乳酸-羟基乙酸共聚物（PLGA）聚合物纳米粒和脂质体制剂，但所得PLGA纳米粒制剂载药量很低，还达不到脂质体制剂的载药量，，没能达到预期效果。而制得的盐酸吡硫醇脂质体制剂，在前人的研究基础上，本研究将其载药量提高一倍，包封率略有增加，刺激性有所降低。本研究对盐酸吡硫醇进行了处方前研究，确定了紫外吸收波长，建立了盐酸吡硫醇HPLC体外分析方法和紫外分光光度法（UV），并进行了方法学验证。还测定了盐酸吡硫醇、盐酸吡硫醇与胆固醇、盐酸吡硫醇与胆固醇硫酸钠、盐酸吡硫醇与胆固醇琥珀酸单酯的油水分配系数，以此考察胆固醇、胆固醇硫酸钠、胆固醇琥珀酸单酯对盐酸吡硫醇油水分配系数的影响，为选定膜流动性调节剂提供了参考。本研究对PLGA聚合物纳米粒的制备工艺和处方筛选进行了考察，但结果表明其载药量低，没有实用价值，因此放弃。在前人的研究基础上，本研究运用薄膜分散法制备了盐酸吡硫醇脂质体，并考察和优化了其制备工艺。工艺方面主要对圆底烧瓶的倾斜角度、溶剂的选用、制备的温度、成膜的速度以及超声的方式进行考察，得到最优工艺，处方方面，将脂质体的包封率作为主要评价指标，筛选了膜稳定剂的用量、所用磷脂的种类、水化介质的离子强度及表面活性剂的种类，最终确定最优处方。并对最优处方制备的制剂进行了表征。最后通过动物模型对脂质体的刺激性进行了初步评价，做了溶血实验验证制剂的安全性。表明刺激性有所降低且未发生很明显的溶血现象。
[Abstract]:Pyritinol hydrochloride is a vitamin B6 analogue that can be used clinically to treat Alzheimer's disease. The main products on the market include pyritinol hydrochloride tablets. Pyritinol hydrochloride injection and pyritinol hydrochloride lyophilized powder injection. According to the feedback of clinical users, the injection has a certain vascular irritation. In order to reduce its vascular irritation, it was prepared into nanometer preparation in this study. The main preparation is lactic acid-glycolic acid copolymer polymer nanoparticles and liposome preparations, but the amount of drug loaded by PLGA nanoparticles is very low, which can not reach the drug load of liposome preparations. The preparation of pyritinol hydrochloride liposome was not able to achieve the desired effect. Based on previous studies, the drug loading was doubled, the entrapment efficiency was slightly increased, and the irritation was decreased. In this study, the pre-prescription study of pyritinol hydrochloride was carried out, the UV absorption wavelength was determined, and the in vitro analysis method and UV spectrophotometric method of pyritinol hydrochloride HPLC were established. The oil and water partition coefficients of pyritinol hydrochloride, pyritinol hydrochloride and cholesterol, pyritinol hydrochloride and sodium cholesterol sulfate, pyritinol hydrochloride and cholesterol succinate monoester were also determined. The effects of cholesterol, sodium cholesterol sulfate and mono-ester of cholesterol succinate on the partition coefficient of pyritinol hydrochloride oil and water were investigated, which provided a reference for the selection of membrane fluidity regulator. In this study, the preparation process and prescription screening of PLGA polymer nanoparticles were investigated, but the results showed that the drug loading was low and had no practical value, so it was abandoned. In this study, pyritinol hydrochloride liposomes were prepared by thin-film dispersion method, and the preparation process was investigated and optimized. The speed of membrane formation and ultrasonic method were investigated to obtain the optimal technology. The encapsulation efficiency of liposome was taken as the main evaluation index. The dosage of membrane stabilizer and the type of phospholipids were selected. The ionic strength of hydration medium and the kinds of surfactants were determined to determine the optimal prescription. The preparation of the optimal prescription was characterized. Finally, the irritability of liposomes was preliminarily evaluated by animal model. The safety of the preparation was verified by hemolysis test, which showed that the irritation was decreased and no obvious hemolysis occurred.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R94

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