摘要
分别采用紫外分光光度法和超高效液相色谱法研究强力霉素原料药与强力霉素壳聚糖纳米粒冻干粉的体内外释药特性。结果表明:强力霉素原料药在人工胃液、肠液和pH7.4磷酸缓冲液中的体外释放均可用零级动力学方程拟合,释放较快,在1h内能完全溶出;强力霉素壳聚糖纳米粒冻干粉具有显著的缓释特性,在各介质中的体外释放均可用双相动力学方程拟合,前期表现为快速释放,后期为缓慢释放,冻干粉在各介质中的释药速率从大到小依次为:pH2.0人工胃液>pH3.0人工胃液>pH4.0人工胃液>人工肠液>pH7.4磷酸盐缓冲液。强力霉素原料药包裹成强力霉素壳聚糖纳米粒冻干粉后,经(25±1)℃20mg/kg单剂量口灌,在斑点叉尾的药—时曲线由双峰变为单峰,在血浆中的血药峰浓度(Cmax)减小,峰值时间(Tmax)和消除半衰期(T1/2β)明显延长,药时曲线下面积(AUC)变大,是一种理想的强力霉素新剂型。
This paper is to study the release characteristics of doxycycline （DC） raw material drug and doxycycline chitosan nanoparticles （DC-CS-NPs） freeze-dried powder in vitro and in vivo by ultraviolet spectrophotometry and ultra performance liquid chromatography, respectively. Results showed that the release behaviors of DC raw material drug were simulated the most in the zero order dynamic equation in artificial gastric juice, artificial intestinal juice and pH 7.4 buffer phosphate. The release of DC raw material drug was fast which could completely dissolve in one hour; The DC-CS-NPs freeze-dried powder had a significant slow-release characteristic. The release behaviors were simulated the most in the biexponential equation. The drug released fast in the early stage while it released slowly later. The order of release speed of DC-CS-NPs freeze-dried powder from fast to slow was pH 2.0 artificial gastric juice, pH 3.0 artificial gastric juice, pH 4.0 artificial gastric juice, artificial intestinal juice and pH 7.4 buffer phosphate. When DC raw material drug became DC-CS-NPs freeze-dried powder, after a single oral administration at a dose of 20 mg/kg at （25±1） ℃, the double-peak phenomenon of plasma in channel catfish was turned into single-peak, and the pharmacokinetic parameters of DC-CS-NPs freeze-dried powder were changed. Compared to DC raw material drug, the peak concentration （Cmax） decreased. The peak time （Tmax） and terminal elimination half-life （T1/2β） prolonged. The area under concentration-time curve （AUC） was larger. The DC-CS-NPs freeze-dried powder will become an ideal DC new formulation.
出处
《水产学报》
CAS
CSCD
北大核心
2012年第6期944-951,共8页
Journal of Fisheries of China
基金
农业部公益性行业科研专项经费项目(201203085)
关键词
斑点叉尾
强力霉素
纳米粒
冻干粉
体外释药
药代动力学
Ictalurus punctatus
doxycycline
nanoparticles
freeze-dried powder
in vitro release
phar-macokinetics
