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天門冬酰胺酶納米囊的藥動(dòng)學(xué)及生物等效性研究

發(fā)布時(shí)間:2018-04-14 06:02

  本文選題:天門冬酰胺酶 + 納米囊; 參考:《食品與生物技術(shù)學(xué)報(bào)》2017年05期


【摘要】:作者研究了載天門冬酰胺酶(Asparaginase,AN)自組裝透明質(zhì)酸-聚乙二醇(Hyaluronic acid-graft-poly(ethylene glycol),HA-g-PEG)/γ-環(huán)糊精(γ-cyclodextrin,γ-CD)納米囊(HA-gPEG/γ-CD nanocapsules loaded with AN,AHRPs)在雄性SD大鼠體內(nèi)的藥代動(dòng)力學(xué)和生物等效性?疾炝薃HRPs的透射電鏡、粒徑、Zeta電位、包封率,并分別測(cè)定大鼠靜脈給予AHRPs和游離AN后,不同時(shí)間點(diǎn)大鼠血漿樣品中AN的活性。采用DAS 2.1.1軟件計(jì)算藥動(dòng)學(xué)參數(shù),對(duì)AHRPs和游離AN進(jìn)行生物等效性評(píng)價(jià)。經(jīng)計(jì)算,AHRPs的平均粒徑為(410.30±3.20)nm,Zeta電位為(-31.40±1.65)m V,平均包封率為(42.80±4.37)%。AHRPs和游離AN的主要藥動(dòng)學(xué)參數(shù)AUC(0~48 h)分別為(104.01±1.68)U/(m L·h)和(46.38±1.98)U/(m L·h),AUC(0~∞)分別為(131.03±19.67)U/(m L·h)和(51.44±3.01)U/(m L·h),t1/2分別為(4.31±1.53)h和(1.86±0.38)h。與游離AN比較,AHRPs的AUC(0~48 h)、AUC(0~∞)和t1/2分別提高了2.24、2.55和2.32倍。AUC(0~48 h)、AUC(0~∞)和Cmax的90%可置信區(qū)間分別為77.1%~78.7%、76.7%~78.3%、98.9%~100.5%。AHRPs延長(zhǎng)了AN在大鼠體內(nèi)的生物半衰期,提高了AN在大鼠體內(nèi)的生物利用度,且AHRPs與游離AN不具有生物等效性。
[Abstract]:The pharmacokinetics and bioequivalence of self-assembled hyaluronic acid-graft-poly(ethylene acid-graft-poly(ethylene HA-g-PEGN / 緯 -cyclodextrin (緯 -CD) nano-capsule HA-gPEG / 緯 -CD nanocapsules loaded with ANAHRPs in male SD rats were studied.The transmission electron microscopy (TEM), particle size potential (Zeta) and encapsulation efficiency of AHRPs were studied, and the activity of an in plasma samples of rats at different time points after intravenous administration of AHRPs and free an were measured respectively.The pharmacokinetic parameters were calculated by DAS 2.1.1 software, and the bioequivalence of AHRPs and free an were evaluated.緇忚綆,

本文編號(hào):1748003

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