马钱子碱固体脂质纳米粒的制备研究01.doc

马钱子碱固体脂质纳米粒的制备研究 吕桦1，宋金春2*，邓睿园1，以盛1 （1.武汉大学药学院，湖北 武汉 430072；2.武汉大学人民医院药学部，湖北 武汉430060） 摘要：目的:以乳化蒸发-低温固化法制备马钱子碱固体脂质纳米粒并评价其质量。方法:在单因素考察的基础上以正交试验设计优化、筛选最佳处方。用透射电镜观察固体脂质纳米粒的形态， HPLC法测定马钱子碱固体脂质纳米粒的包封率, 激光散射测定Zeta电位和粒度分布，并考察其稳定性。结果:所制固体脂质纳米粒外观形态圆整，平均粒径为116 nm，Zeta电位为-29.9mV,包封率为50.7％。4℃放置1个月，粒径、包封率无明显变化。结论:本研究制备的马钱子碱固体脂质纳米粒粒径分布窄，稳定性好,为开发马钱子碱低毒长效的制剂奠定了实验基础。 关键字:固体脂质纳米粒；马钱子碱；包封率；稳定性；正交试验 [中图分类号] R943；R971.1 [文献标识码] A Preparation and Quality Evaluation of Brucine solid lipid nanoparticles LV Hua1, SONG Jin-chun2*, DENG Rui-yuan1, YI Sheng1 (1.College of pharmacy, Wuhan university, Wuhan 430072, China ；2.Department of pharmacy, Renmin Hospital of Wuhan university, Wuhan 430060,China) OBJECTIVE:To prepare Brucine solid lipid nanoparticles(Bru-SLN) by means of emulsification- solvent evaporation method and to evaluate its quality.METHODS:The formulation of Bru-SLN were optimized by the orthogonal design on the basis of single factor exploration.The morphology was examined by the transmission electron microscope.High-performance of liquid chromatography was employed to determine the entrapment efficiency of Bru-SLN.The diameter,zeta potential and the stability of Bru-SLN were investigated．R:The obtained solid lipid nanoparticles were round,smooth particles with average size of 116 nm,zeta potential -29 mV and entrapment efficiency 50.1%.There were no notable changes of the particle size and entrapment efficiency at 4 ℃ within one month. CONCLUSION:Bru-SLN shows a narrow particle size distribution and good stability,which can be a promising low-toxicity and long-effect preparation. KEY WORDS: Solid lipid nanoparticles ; Brucine ; Preparation Orthogonal design 马钱子碱(Brucine)是中药马钱子的主要成分之一，临床效果非常好，主要用于镇痛、消炎，亦可用于胃癌,肠癌,肺癌,肝癌,白血病等癌症，具有广泛的药理作用[1-3]。但是马钱子碱是剧毒药物，其治疗量和中毒量接近,安全范围小，稍有不甚使用过量易引起中枢毒性，如恐惧，癫痫样发作等，并且具有口干，头晕，头痛和胃肠道刺激等不良反应，使其临床应用受到极大了限制。同时，马钱子碱给药后血药浓度达峰时间短，代谢快，体内蓄积少。为了降低其毒性反应、延长在体内的作用时间，近几年出现的超细粉碎技术、纳米技术等药物新制剂新技术的发展以及中医理论的配伍方式都为马钱子碱减毒、提效提供了可能[4]。固体脂质纳米粒是近十几年来发展起来的一种新型给药系统, 是指粒径在1