鸦胆子油脂质体冻干粉的制备及其药剂学行为考察

【作者】 徐琳；

【导师】 胡荣；

【作者基本信息】 扬州大学 ， 中药学， 2008， 硕士

【摘要】 本研究的主要目的是制备稳定性良好的鸦胆子油脂质体冻干粉,并对其进行药剂学行为考察,为鸦胆子油脂质体冻干粉制剂的研发提供基础实验依据。鸦胆子油是从苦木科植物鸦胆子成熟果实中提取而得的油脂类物质。现代药理学研究表明鸦胆子油具有抗癌、抗病原体、抗氧化、抗胃溃疡等作用。临床上将其制成10%鸦胆子油乳剂,作为辅助抗肿瘤药物,用于治疗消化系统肿瘤[1~8]。乳剂属于多相动力学不稳定分散体系,在受热、受冷及长期储存过程中均能引起乳析和破裂,渗漏的鸦胆子油毒性大,对胃肠粘膜和血管壁的刺激性也很严重。本文为增强鸦胆子油的疗效和制剂稳定性,降低毒副作用,研制了鸦胆子油脂质体。并采用冷冻干燥技术制备脂质体冻干粉。其主要优点在于:制剂以固体形式保存,稳定性得到了很大的提高,鸦胆子油脂质体冻干粉可直接口服,也可加水分散后通过其他途径给药。采用紫外分光光度法测定鸦胆子油脂质体中鸦胆子油的含量,建立标准曲线,回归方程为:A = 0.4936 C + 0. 0144 ,r = 0. 9991。该方法的精密度、回收率均符合要求。本研究采用已有处方制备空白脂质体,添加高分子辅料,以包封率为考察指标,制备鸦胆子油脂质体,确定最佳处方为:鸦胆子油﹕空白脂质体溶液=2.4﹕10,平均包封率可达94.31%。透射电镜观察,脂质体大多为单室结构,粒子呈圆形或椭圆形,分布较均匀,平均粒径130nm左右。粘度值为4.275pa﹒s,pH:6.45,Zeta电位:-23.4213±0.39mV。采用冷冻干燥技术制备鸦胆子油脂质体冻干粉,考察影响冻干效果的关键工艺过程,确定最佳制备工艺:预冻温度47℃、预冻速度为快速降温、预冻时间为4h、真空干燥时间为34h。通过显微镜观察、复水实验、冻干前后粒径大小及分布、包封率等观察指标对冻干保护剂进行种类筛选及量的考察,正交实验确定最佳保护剂及处方为:磷脂与蔗糖、甘露醇、海藻糖的比例为1﹕1.5﹕2﹕2。考察了鸦胆子油脂质体冻干粉的理化性质,脂质体冻干粉外观白色,饱满,平均粒径为140nm左右,pH:6.45,Zeta电位:-23.1058±0.21mV,包封率为:92.22%。进行了鸦胆子油脂质体冻干粉的体外释药实验,绘制鸦胆子油脂质体冻干粉的体外释放曲线,用方程进行拟和,考察相关系数。结果表明鸦胆子油经脂质体包裹后具有一定的缓释效果。更多还原

【Abstract】 The purpose of this study is to examine the stability of good quality oleum fructus bruceae of freeze-dried powder, in vitro study of its release, as oleum fructus bruceae quality freeze-dried powder of the research and development to provide the basic experimental basis.oleum fructus bruceae,the oil type substances, is extracted from the hard wood species oleum fructus bruceae’s ripe fruit. Modern pharmacological research shows that oleum fructus bruceae has anti-cancer, anti-pathogens, anti-oxidation, anti-ulcer effect, and so on. 10 percent of oleum fructus bruceae is made for clinical use, as a supplement anti-cancer drug for the treatment of digestive system cancer.As for oleum fructus bruceae emulsion, there is the issue of multi-phase emulsion decentralized system of unstable dynamics, heat, cold and the long-term use can be stored in milk out and caused the breakdown. Leakaged toxic oleum fructus bruceae, will seriously irritation the gastrointestinal Mucous membrane, as well as the vessel wall. In order to enhance the oleum fructus bruceae’s efficacy and increase it’s stability, low toxicity and side effects without affecting its anti-tumor activity, we have developed a body of oleum fructus bruceae lipsome.To enhance the stability of liposome, we used freeze-drying technology to make the freeze-dried liposome powder. The main advantage is that: the solid form of preservation, stability has been greatly improved by simply adding water and stirring. Freeze-dried liposome powder is easily and quickly to be redeveloped, while the physical and chemical properties were little changed.Adopting the ultraviolet spectrophotometry to determinate the oleum fructus bruceae content of the oleum fructus bruceae lipsomes, establish the standard curve, and the regression equation is: A = 0.4936 C + 0. 0144, r = 0. 9991. The precision and recovery of this method had complied with the request.This study used the prescription and added polymer materials to prepare blank liposomes.By studying for the encapsulation efficiency, we have determined the best prescription, that is: oleum fructus bruceae: blank liposome solution = 2.4:10, the average rate of encapsulation eddiciency is 94.32 percent. Liposomes were observed for the single-room structure, the particles are round or oval, more even distribution, and the average size is around 130 nm. Viscosity value was 4.275pa.S, pH: 6.45, Zeta potential: -23.1058 mV.Adopting the freeze-drying technology to prepare the oleum fructus bruceae freeze-dried powder of liposomes. Studying the key effects of freeze-dried process, we have determined the best preparation process, that is: pre-freezing temperature: 47℃, pre-frozen for the fast speed cooling, pre-freeze time for 4 h, vacuum drying time for 32 h. Through the microscope, rehabilitation with water, freeze-dried before and after size and distribution of the particle, encapsulation efficiency and so on as observation indicators for the screening of the types of the freeze-dried agents and determine the best prescription, that is: phospholipid and mannitol: trehalose for 1:2:2:3.Inspecting the quality of the physical and chemical properties of the freeze-dried powder, The appearance of the liposome freeze-dried powder is white and full, the average size is around140nm, pH: 6.45, Zeta potential: -23.4213 mV, encapsulation efficiency:92.22%.We have carried out the vitro release experiment of the oleum fructus bruceaa liposome freeze-dried powder. effect. Drawing the vitro release curves of the oleum fructus bruceaa. Equations were used and to study the correlation coefficient.The results showed that the oeum fructus bruceaa after being packaged by the liposome has a sustained-release更多还原