摘要
目的:研究聚乙二醇-(聚乳酸-羟基乙酸)-聚乙二醇三嵌段共聚物(PELGE)-克班宁纳米粒(PELGE-Cre-NPs)在家兔体内的药动学。方法:取6只家兔,耳缘静脉注射PELGE-Cre-NPs(3.5 mg/kg),分别于给药后5、15、30、60、90、120、150、180、240、300min时,于其耳缘静脉采血1 m L。分离血浆,用乙酸乙酯萃取Cre,并采用高效液相色谱法,以盐酸维拉帕米为内标,测定Cre的血药浓度,然后采用DAS 2.0软件绘制血药浓度-时间曲线并计算药动学参数。色谱条件采用色谱柱为Agilent ZORBAX ExtendC18,流动相为甲醇-0.01%三乙胺溶液(75∶25,V/V),流速为1 m L/min,检测波长为280 nm,柱温为30℃,进样量为20μL。结果:Cre检测血药浓度的线性范围为45.0~3 600μg/L(R^2=0.999 9),日内、日间精密度试验和稳定性试验的RSD均小于5%(n=6或n=12),准确度为(97.44±2.41)%^(98.45±3.87)%(n=6)。PELGE-Cre-NPs在家兔体内分布符合二室模型;主要药动学参数t1/2为(109.357±33.917)min,CL为(0.016±0.001)L/(min·kg),MRT为(76.733±7.502)min,cmax为(3 699.458±287.713)μg/L。结论:PELGE-Cre-NPs在家兔体内的半衰期较Cre注射剂长,滞留时间延长,有缓释效果。
OBJECTIVE:To study the pharmacokinetics of PELGE-crebanine nanoparticles(PELGE-Cre-NPs)in rabbits.METHODS:Totally 6 rabbits were collected,and injected with PELGE-Cre-NPs(3.5 mg/kg)via ear vein.1 mL of blood samples were collected at 5,15,30,60,90,120,150,180,240,300 min after administration from the ear vein.After the plasma were isolated and Cre were extracted with ethyl acetate,HPLC method was adopted to determine the plasma concentration of Cre by using verapamil hydrochloride as internal standard.The plasma concentration-time curve was drawed and pharmacokinetic parameters were calculated by using DAS 2.0 software.Chromatographic conditions such as the chromatographic column was Agilent ZORBAX Extend-C18;the mobile phase consisted of methanol-0.01%triethylamine solution(75∶25,V/V);the flow rate was 1 mL/min;the detection wavelength was 280 nm;the column temperature was 30℃;the injection volume was 20μL.RESULTS:The linear range of Cre were 45.0-3600μg/L(R^2=0.9999).RSDs of inter-day and intra-day precision and stability tests were all lower than 5%(n=6 or n=12);the accuracies were(97.44±2.41)%-(98.45±3.87)%(n=6).PELGE-Cre-NPs was in a two-compartment model in rabbits.Main pharmacokinetic parameters included that t1/2 was(109.357±33.917)min;CL was(0.016±0.001)L/(min·kg);MRT was(76.733±7.502)min;cmax was(3699.458±287.713)μg/L.CONCLUSIONS:The half-life period of PELGE-Cre-NPs in rabbits is longer than that of Cre injection;its retention time in the body is prolonged,and sustained-release effect is obvious.
作者
孔淑君
蔡俊飞
孙杏倩
刘云宽
马云淑
KONG Shujun;CAI Junfei;SUN Xingqian;LIU Yunkuan;MA Yunshu(College of TCM,Yunnan University of TCM,Kunming 650500,China;Disha Pharmaceutical Group Co.,Ltd.,Shandong Weihai 264200,China;Yunnan Key Laboratory of Aromatic Drugs in Universities,Kunming 650500,China;Yunnan Key Laboratory of External Drug Delivery System and Preparation Technology in Universities,Kunming 650500,China)
出处
《中国药房》
CAS
北大核心
2020年第7期778-781,共4页
China Pharmacy
基金
国家自然科学基金资助项目(No.81673682,No.81260651)
云南省科技厅-云南中医学院应用基础研究联合专项重点项目(No.2018FF001008)。
