氧化苦参碱磷脂复合物固体脂质纳米粒冻干粉的制备与质量评价  

Preparation of Oxymatrine Phospholipid Complex Solid Lipid Nanoparticles Lyophilized Powder and Evaluation of Its Quality

作　　者：严俊丽[1] 李婉蓉 杨佳佳 王益[1] 贺智勇[1] 姜丰[1] 周雪[1] 吴林菁[1] 甘诗泉 王恒[2] 沈祥春[1] 陶玲[1] YAN Jun-li;LI Wan-rong;YANG Jia-jia;WANG Yi;HE Zhi-yong;JIANG Feng;ZHOU Xue;WU Lin-jing;GAN Shi-quan;WANG Heng;SHEN Xiang-chun;TAO Ling(State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Provincial Engineering Center of Efficient Utilization of Natural Medicine Resources,High Educational Key Laboratory of Natural Medicinal Pharmacology and Druggability of Guizhou Province,Key Laboratory of Optimal Utilization of Natural Medicinal Resources,Guizhou Medical University,Guiyang 550025,China;Qiannan Medical College for Nationalities,Duyun 558003,China)

机构地区：[1]贵州医科大学省部共建药用植物功效与利用国家重点实验室贵州省天然药物资源高效利用工程中心贵州省高等学校天然药物药理与成药性评价特色重点实验室天然药物资源优效利用重点实验室,贵阳550025 [2]黔南民族医学高等专科学校,贵州都匀558003

出　　处：《中国实验方剂学杂志》2019年第7期146-152,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：贵州省高层次创新型人才百层次人才项目(贵州科技厅黔科合人才[2015] 4029号);贵州医科大学药学国际科技合作基地项目(黔科合平台人才[2017]5802);贵州省科学技术基金重点项目(黔科合JZ字[2015]2002号);黔南州科技计划项目(黔南科合社字[2017]74号);遵义医学院基础药理省部共建教育部重点实验室项目(黔教合KY字[2017]379);贵阳医学院博士启动基金项目(院博合J字[2017-24]号);贵州省教育厅青年科技人才成长项目(黔教合KY字[2018]181)

摘　　要：目的:制备氧化苦参碱磷脂复合物固体脂质纳米粒(OMT-PC-SLN)冻干粉,并对其进行药剂学性质评价。方法:采用伪三元相图优选微乳处方;以包封率为指标,采用单因素试验优选OMT-PC-SLN冻干粉的处方工艺;利用透射电子显微镜(TEM)观察该制剂的外观形态,激光粒度仪测定粒径,并考察OMT-PC-SLN冻干粉的体外释药性能。结果:最佳处方工艺为大豆磷脂和15-羟基硬脂酸聚乙二醇酯(Kolliphor HS 15)为乳化剂,乙醇为助乳化剂,乳化剂与助乳化剂的比例(Km)=3∶2,油相∶(乳化剂+助乳化剂)=1∶9,氧化苦参碱磷脂复合物-硬脂酸-大豆磷脂-Kolliphor HS 15-乙醇(30∶100∶180∶360∶360);含4%甘露醇的水50 m L为外水相,1 000 r·min-1冰浴搅拌固化1 h,于-20℃预冻24 h,取出,干燥24 h。OMT-PC-SLN冻干粉外观呈类球形,包封率(38. 09±1. 24)%,平均粒径785. 5 nm,多分散系数(PDI) 0. 456,Zeta电位-24. 82 m V;体外释放结果表明OMT-PC-SLN冻干粉2 h时累积释放率72. 63%,12 h累积释放率98. 42%,原料药在2 h的累积释放率98. 60%。结论:优选的OMT-PC-SLN冻干粉处方工艺稳定、重复性好;与原料药相比,OMT-PC-SLN冻干粉体外释放较慢,具有一定的缓释效果。Objective:To prepare oxymatrine phospholipid complex solid lipid nanoparticles(OMT-PCSLN)lyophilized powder and evaluate its pharmaceutical properties.Method:Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion;single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index;the morphology of this preparation was observed by transmission electron microscope(TEM).The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined.Result:Optimal formulation process was as following:taking soybean phospholipid and polyethylene glycol 15-hydroxystearate(Kolliphor HS 15)as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier(Km)=3 ∶ 2,oil phase ∶(emulsifier + co-emulsifier)=1 ∶ 9,oxymatrine phospholipid complex-stearic acidsoybean phospholipid-Kolliphor HS 15-ethanol(30 ∶ 100 ∶ 180 ∶ 360 ∶ 360);taking 50 mL of 4% mannitol solution as the external aqueous phase,ice bath stirring at 1000 r·min^-1 and solidifying for 1 h,precooled at-20 ℃ for24 h,took out and dried for 24 h.OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of(38.09 ± 1.24)%,average particle size of 785.5 nm,polydispersity coefficient(PDI)of 0.456 and the Zeta potential of-24.82 mV.The cumulative release rates of OMT-PC-SLN lyophilized powder were 72.63% at 2 h and 98.42% at 12 h;the cumulative release rate of oxymatrine(crude drug)was98.60% at 2 h.Conclusion:This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability;compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.

关 键 词：氧化苦参碱磷脂复合物 伪三元相图法 固体脂质纳米粒 冻干粉 体外释药性能 包封率 冻干保护剂 

分 类 号：R22[医药卫生—中医基础理论] R94[医药卫生—中医学]