【作者】 刘倩；

【导师】 周燕文；

【作者基本信息】 广西医科大学 ， 药理学， 2007， 硕士

【摘要】 目的:本课题研究以大豆卵磷脂等为载体材料制备苦参素(Marine)脂质体,探索出一种较稳定的、包封率较高的苦参素脂质体的制备方法,并对苦参素脂质体进行质量评价。方法:采用氧化指数法对购得的载体材料进行检测;通过测定苦参素的表观正辛醇.水分配系数,得到苦参素的表观油/水分配系数;考察薄膜分散法、逆相蒸发法、熔融法、复乳法、pH梯度法、硫酸铵梯度法制备苦参素脂质体的可行性,选择其中包封率高的制备方法,进一步优选制备工艺;建立脂质体中苦参素含量测定的高效液相色谱法(HPLC);用分段收集流分进行HPLC测定的方法考察了葡聚糖凝胶过滤法分离含药脂质体与游离药物的可行性。选择复乳法作为苦参素脂质体的制备方法,以外观形态和包封率为考察指标优选最佳处方及最佳工艺,首先采用以单因素方法进行初步筛选,再用正交试验设计方法确定最佳制备工艺和处方。研制了苦参素多囊脂质体。用倒置相差显微镜观察脂质体的形态;用纳米粒度分析仪测定平均粒度和粒度分布;通过测定脂质体的渗漏率初步考察脂质体的稳定性;用动态透析法考察苦参素多囊脂质体的体外释药特性。结果:用氧化指数测定合格的大豆卵磷脂作为载体材料制备苦参素脂质体,以复乳法制备的苦参素多囊脂质体包封率最高,为50%以上;制得的苦参素多囊脂质体呈乳白色、均匀、混悬状态;在显微镜下观察为圆形、椭圆形粒子,平均粒度为745nm,80～89%的粒子粒度在500～800nm之间;初步稳定性试验研究表明,本制剂在5℃条件下放置一个月较稳定;苦参素多囊脂质体体外释放度试验研究表明,0.5小时内药物的累积释放量约40%,累积药物释放百分含量与Higuchi方程吻合良好。结论:复乳法制备苦参素多囊脂质体的工艺可行,大大提高了苦参素脂质体的包封率,体外释放度试验表明本制剂有一定的缓释性,基本达到试验设计的预期目的。更多还原

【Abstract】 Objective:To study the preparation technology packaged marine with soya bean phosphatidylcholine et al.To explore the more stable and higher entrapment efficiency(EE,%)preparation method of the marine liposomes and evaluate their quality.Methods:Firstly,we studied the membrane material purchased in the market by oxidizing index method,the result showed that the soybean phosphatide fulfiled the requirement.Determined by the apparent n-octyl alcohol/water distribution coefficient,we attained the apparent octanol/water distribution coefficient of marine.The liposomes were prepared by the following methods:film dispersion technology,reverse-phase evaporation technology,melting technology, reduplicative emulsification technology,pH gradient technology,ammonium sulfate gradient technology.EE was determined with HPLC of continuous flowing liquid from the column of Sephadex G50.To determine the encapsulation of liposomes we used the reduplicative emulsification technology,choosing the single factors firstly,optimized method by orthogonal design and came out the best technology.Weighed by appearance and EE of in liposome,we prepared the marine-multivesicular liposomes (marine-MVL).In this paper,we observed the appearance by inverted phase contrast microscope,measured the particle diameter by nanometer particle size apparatus,examined the dissolution profiles in vivo using dynamoic dialyzetion. Results:Research indicated,the EE measuration was reliable,and measured the average EE of marine-MVL was more than 50%.The results showed that using the defined method,we prepared good marine-MVL,it had cream colored、well-distributed、suspensoid appearance;round and oval granule appearance through inverted phase contrast microscope,and the equally diameter was 745nm,well-distributed particle size distribution,as 80%～89%was during 500～800nm.The initial stability test displayed that the product was stable in 5℃for one month.In vivo experiment showed that the relation of culminateve drug and time accord to Higuchi equation.Conclusions:The experiments make clear that the reduplicative emulsification technology was feasible and repeatable.The vivo experiment proved they had a good slow-release capability.For basic,we had attained what we want as we expected.更多还原