静脉注射尿酸酶多囊脂质体的药代动力学和药效学研究

发布时间：2018-05-24 16:58

  本文选题：尿酸酶 + 多囊脂质体　； 参考：《四川大学学报(医学版)》2015年05期

【摘要】：目的研究尿酸酶多囊脂质体(uricase-multivesicular liposomes,UOMVLs)在大鼠体内的药代动力学,并与游离尿酸酶(uricase,UOX)进行药代动力学和药效学比较。方法采用复乳法制备UOMVLs,检测UOMVLs包封率、粒径和Zeta电位。将12只健康雄性SD大鼠随机分为2组,分别静脉注射UOMVLs和UOX进行干预治疗,测定给药后不同时间点大鼠血清中尿酸酶的活性,用DAS 2.1.1软件进行药代动力学参数计算。另取24只雄性SD大鼠,模型组采用次黄嘌呤和氧嗪酸钾建立高尿酸大鼠模型(n=6),UOMVLs组(n=6)和UOX组(n=6)分别于建模后1h静脉注射1mL(0.47U/mL)UOMVLs和游离UOX,并以正常组(n=6)为对照,于建模后1、2、3、5、7、9、12、24、36、48h测定大鼠血清中尿酸水平。对其降尿酸作用进行考察。结果制备的UOMVLs包封率为(63.75±3.65)%,粒径为(22.56±1.70)μm,Zeta电位为(-41.81±6.59)mV。大鼠静脉注射UOMVLs和UOX后,药时曲线下面积(AUC0-∞)分别为(498.83±58.85)和(28.49±9.95)U/L·h;达峰时间(Tmax)分别为(1.00±0.00)和(0.00±0.00)h;峰浓度(Cmax)分别为(73.04±6.35)和(31.00±6.03)U/L;半衰期(t1/2)分别为(3.49±0.80)和(1.17±0.33)h;UOMVLs相对于UOX的生物利用度为(1 750.90±206.56)%。UOMVLs和UOX药效学特性分析显示,UOMVLs干预治疗9h大鼠血尿酸水平降至正常组水平,而UOX干预治疗48h大鼠血尿酸水平才与模型组一样降至正常组水平。结论将UOX制备成UOMVLs后Tmax延后,t1/2延长,生物利用度明显提高;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 卤3.65 and the particle size was 22.56 卤1.70) 渭 m Zeta potential was -41.81 卤6.59 mV. After intravenous injection of UOMVLs and UOX, 鑽�鏃舵洸绾夸笅闈㈢В�

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