波棱素脂质体冻干粉针的制备及初步安全性和药效学研究  

Preparation of herpetin lyophilized liposome and evaluation on its safety and pharmacodynamics

作　　者：张鑫[1] 谭睿[2] 顾健[1] 何黎黎[1] 章雷[1] 龚普阳 

机构地区：[1]西南民族大学民族医药研究院,四川成都610041 [2]西南交通大学生命科学与工程学院,四川成都610031

出　　处：《中国中药杂志》2014年第16期3065-3068,共4页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81674168);四川省科学支撑项目(2011FZ0053);四川省应用基础研究项目(2012JY0027)

摘　　要：该文研究了波棱素(herpetin,HPT)脂质体冻干粉针剂的制备方法,并对其初步安全性和药效学进行评价。采用薄膜分散法制备HPT脂质体溶液,以包封率、粒径等为评价指标,筛选最佳冻干保护剂;对冻干粉针进行稳定影响因素实验,并初步研究了HPT脂质体冻干粉针的安全性以及对CCl4所致急性肝损伤模型小鼠的治疗效果。质量分数5%乳糖+5%蔗糖为最佳冻干保护剂,按照最优处方制得的脂质体冻干粉针复水后,平均包封率为(99.70±0.50)%,平均粒径为(107.0±1.2)nm,平均电位为(-6.11±0.72);脂质体冻干粉针对温度、湿度及光照均较为敏感;脂质体冻干粉针复水后不会引起溶血和红细胞聚集反应,静脉注射对血管亦无明显影响;HPT脂质体对CCl4所致急性肝损伤模型小鼠的治疗效果明显,血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)指标水平均明显改善,治疗效果明显优于HPT原药。按照最优处方制备的波棱素脂质体冻干粉复水后粒径均匀,包封率符合《中国药典》要求,且具有较高的安全性,能显著提高HPT的治疗效果,保存时应该注意低温、避光、密封保存。In this study,the herpetin（ HPT） lyophilized liposome was prepared,and its safety and pharmacodynamics were evaluated. HPT lyophilized liposome was prepared by thin-film ultrasonication method. The lyoprotectant was optimized using particle size and encapsulation efficiency as indexes. Then,the influencing factors of HPT lyophilized liposome were investigated. In addition,preliminary safety and therapy efficiency of HPT lyophilized liposome to liver injury induced by CCl4 in the mice. The optimal lyoprotectant was 5% sucrose plus 5% lactose and the dispersed HPT lyophilized liposomes were spherical with the mean diameter of（ 107.0 ±1.2） nm and the mean encapsulation efficiency of（ 99.7 ±0.50） %. The lyophilized powder was sensitive to temperature,humidity and illumination. None of hemolysis,hemagglutination and vein irritation was observed after intravenous injection of HPT lyophilized liposomes into rabbits. HPT lyophilized liposome showed obviously therapy efficiency to liver injury induced by CCl4 in the mice.The improvements of ALT,AST and ALP were better than that in HPT free drug. The obtained HPT lyophilized liposome met the standard of CP with fine particle size and encapsulation efficiency after dispersion. The HPT lyophilized liposome showed good safety and enhanced the treatment efficacy of HPT. The HPT lyophilized liposome should be stored in low temperature,sealed condition far away from light.

关 键 词：波棱素 脂质体 粉针剂 安全性 药效学 

分 类 号：R29[医药卫生—民族医学]