本文選題：尿酸酶 + 多囊脂質(zhì)體�。� 參考：《四川大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)》2015年05期

【摘要】：目的研究尿酸酶多囊脂質(zhì)體(uricase-multivesicular liposomes,UOMVLs)在大鼠體內(nèi)的藥代動(dòng)力學(xué),并與游離尿酸酶(uricase,UOX)進(jìn)行藥代動(dòng)力學(xué)和藥效學(xué)比較。方法采用復(fù)乳法制備UOMVLs,檢測(cè)UOMVLs包封率、粒徑和Zeta電位。將12只健康雄性SD大鼠隨機(jī)分為2組,分別靜脈注射UOMVLs和UOX進(jìn)行干預(yù)治療,測(cè)定給藥后不同時(shí)間點(diǎn)大鼠血清中尿酸酶的活性,用DAS 2.1.1軟件進(jìn)行藥代動(dòng)力學(xué)參數(shù)計(jì)算。另取24只雄性SD大鼠,模型組采用次黃嘌呤和氧嗪酸鉀建立高尿酸大鼠模型(n=6),UOMVLs組(n=6)和UOX組(n=6)分別于建模后1h靜脈注射1mL(0.47U/mL)UOMVLs和游離UOX,并以正常組(n=6)為對(duì)照,于建模后1、2、3、5、7、9、12、24、36、48h測(cè)定大鼠血清中尿酸水平。對(duì)其降尿酸作用進(jìn)行考察。結(jié)果制備的UOMVLs包封率為(63.75±3.65)%,粒徑為(22.56±1.70)μm,Zeta電位為(-41.81±6.59)mV。大鼠靜脈注射UOMVLs和UOX后,藥時(shí)曲線下面積(AUC0-∞)分別為(498.83±58.85)和(28.49±9.95)U/L·h;達(dá)峰時(shí)間(Tmax)分別為(1.00±0.00)和(0.00±0.00)h;峰濃度(Cmax)分別為(73.04±6.35)和(31.00±6.03)U/L;半衰期(t1/2)分別為(3.49±0.80)和(1.17±0.33)h;UOMVLs相對(duì)于UOX的生物利用度為(1 750.90±206.56)%。UOMVLs和UOX藥效學(xué)特性分析顯示,UOMVLs干預(yù)治療9h大鼠血尿酸水平降至正常組水平,而UOX干預(yù)治療48h大鼠血尿酸水平才與模型組一樣降至正常組水平。結(jié)論將UOX制備成UOMVLs后Tmax延后,t1/2延長(zhǎng),生物利用度明顯提高;UOMVLs比UOX更有效降低高尿酸模型大鼠血清中尿酸水平。
[Abstract]:Objective to study the pharmacokinetics of uricase-multivesical liposome UOMVLs in rats and compare the pharmacokinetics and pharmacodynamics of uricase with free uricase (UOX). Methods UOMVLs were prepared by double emulsion method. The encapsulation efficiency, particle size and Zeta potential of UOMVLs were measured. Twelve healthy male Sprague-Dawley rats were randomly divided into two groups. UOMVLs and UOX were injected intravenously to treat the rats. The serum uric acid enzyme activity was measured at different time points after administration. The pharmacokinetic parameters were calculated by DAS 2.1.1 software. Another 24 male Sprague-Dawley rats were treated with Hypoxanthine and potassium oxazinate to establish hyperuricemia rat model, the two groups were given 1mL(0.47U/mL)UOMVLs and free UOX intravenously at 1 hour after modeling, and the normal group was used as control. The level of uric acid in serum of rats was determined after modeling for 48 hours. Its effect on reducing uric acid was investigated. Results the entrapment efficiency of UOMVLs was 63.75 鹵3.65 and the particle size was 22.56 鹵1.70) 渭 m Zeta potential was -41.81 鹵6.59 mV. After intravenous injection of UOMVLs and UOX, 鑽椂鏇茬嚎涓嬮潰縐，

本文編號(hào)：1929851