岩白菜素纳米结构脂质载体制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of bergenin nanostructured lipid carriers

作　　者：丁玉[1] 张艳慧[1] 辛娟 崔琳[2] 马春芬[3] DING Yu;ZHANG Yan-hui;XIN Juan;CUI Lin;MA Chun-fen(Huanghe Science and Technology College,Zhengzhou 450006,China;The First Hospital Affiliated to Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan Provincial Hospital of Traditional Chinese Medicine,Zhengzhou 450002,China)

机构地区：[1]黄河科技学院,河南郑州450006 [2]河南中医药大学第一附属医院,河南郑州450046 [3]河南省中医院,河南郑州450002

出　　处：《中成药》2023年第12期3865-3871,共7页Chinese Traditional Patent Medicine

基　　金：国家级大学生创新创业训练计划项目(202211834015);河南省高校教学名师项目(豫教[2022]27570);郑州地方高校技术技能名师工作室项目(郑教高函[2021]380号);郑州市名师工作室项目(郑教师函[2022]438号)。

摘　　要：目的制备岩白菜素纳米结构脂质载体,并考察其体内药动学。方法熔融法制备纳米结构脂质载体。以固态脂质种类、液态脂质种类、固液脂质比、脂药比、泊洛沙姆188浓度为影响因素,包封率、载药量、粒径为评价指标,单因素试验优化处方,考察体外释药,测定稳定性,进行晶型分析。18只大鼠随机分为3组,分别灌胃给予岩白菜素、物理混合物、岩白菜素纳米结构脂质载体的0.5%CMC-Na混悬液(60 mg/kg),于0.25、0.5、1、2、3、4、5、6、8、10、12 h采血,HPLC法测定岩白菜素血药浓度,计算主要药动学参数。结果最优处方为固态脂质山嵛酸甘油酯,液态脂质油酸,固液脂质比4∶1,脂药比10∶1,泊洛沙姆188浓度2.0%,平均包封率为(84.16±1.57)%,载药量为(7.73±0.27)%,粒径为(215.53±18.04)nm,Zeta电位为-(37.56±2.03)mV。纳米结构脂质载体在模拟胃液中240 min内累积释放度小于50%,在模拟肠液中36 h内为71.04%,并且在后者中12 h内稳定性良好。岩白菜素以无定形状态存在于纳米结构脂质载体中。与原料药、物理混合物比较,纳米结构脂质载体t_(max)、t_(1/2)延长(P<0.01),C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.01),相对生物利用度与原料药相比增加至6.08倍。结论纳米结构脂质载体可改善岩白菜素稳定性、口服生物利用度。AIM To prepare bergenin nanostructured lipid carriers,and to investigate their in vivo pharmacokinetics.METHODS The nanostructured lipid carriers were prepared by melting method.With solid lipid type,liquid lipid type,solid-liquid lipid ratio,lipid-drug ratio and poloxamer 188 concentration as influecing factors,encapsulation efficiency,drug loading and particle size as evaluation indices,the formulation was optimized by single factor test,after which the in vitro drug release was investigated,the stability was determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of bergenin,physical mixture and bergenin solid dispersions(60 mg/kg),respectively,after which blood collection was made at 0.25,0.5,1,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of bergenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be glyceryl behenate as solid lipid,oleic acid as liquid lipid,4∶1 for solid-liquid lipid ratio,10∶1 as lipid-drug ratio 2.0%for poloxamer 188 concentration,the average concentration,drug loading,particle size and Zeta potential were(84.16±1.57)%,(7.73±0.27)%and(215.53±18.04)nm and-(37.56±2.03)mV,respectively.The nanostructured lipid carriers demonstrated the accumulative release rate of less than 50%within 240 min in simulated gastric fluid,which was 71.04%within 36 h in simulated intestinal fluid,along with good stability within 12 h in the latter.Bergenin existed in the nanostructured lipid carriers in an amorphous state.Compared with raw medicine and physical mixture,the nanostructured lipid carriers displayed prolonged t max and t 1/2(P<0.01),and increased C_(max),AUC_(0-t),AUC_(0-∞)(P<0.01),whose relative bioavailability was enhanced to 6.08 times as compared with that of raw medicine.CONCLUSION Nanostructured lipid carriers can improve the stability and oral bioavailability of bergenin.

关 键 词：岩白菜素 纳米结构脂质载体 制备 体内药动学 熔融法 HPLC 

分 类 号：R944[医药卫生—药剂学]