山茱萸总甙滴眼液眼内药代动力学及药效学的实验研究  

Studies on pharmacokinetics and pharmacodynemics of cornus officinalis glycosides eye-drops

作　　者：孟晶[1] 李辰[1] 陈建苏[1] 赵松滨[1] 狄静芳[2] 杨皓庄[3] 张穗梅[3] 

机构地区：[1]暨南大学医学院第一附属医院眼科,广东广州510630 [2]暨南大学组织移植与免疫研究中心 [3]暨南大学医学院病理生理学教研室,广东广州510632

出　　处：《暨南大学学报（自然科学与医学版）》2002年第4期5-10,共6页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：广东省医学科研基金 (A2 0 0 2 32 2 );广东省中医药管理局科研基金资助 (30 2 0 0 4)

摘　　要：目的 :研制出山茱萸总甙 (COG)滴眼液 ,对该滴眼液的药代动力学进行研究 ,并观察其局部应用对角膜移植免疫排斥反应的影响。方法 :用高效液相色谱法对该滴眼液的药代动力学参数进行研究。建立封闭群大鼠角膜移植模型 ,随机分为 4组 :A组为空白对照组 ,B、C、D组分别为使用质量分数 0 5 %、1%和 2 %COG滴眼液组。用裂隙灯显微镜记录及比较各组角膜排斥反应发生时间。结果 :COG滴眼液在新西兰白兔眼内为一室模型 ,主要药代动力学参数为 :A =4 316 μg/mL ,Ke=2 0 5 6h- 1,Ka=2 5 79h- 1,LagTime =0 198h ,t1/ 2 ,Ka=0 0 2 3h ,t1/ 2 ,Ke=0 2 5 7h ,Tmax=0 986h ,ρmax=1 2 94 μg/mL ,AUC =1 6 0 1μg·h/mL ,其拟合的动力学方程为 ρ(t) =10 6 0 5×Dose×(e- 2 0 56× (t- 0 198) -e- 2 579× (t- 0 198) )。术后各组发生角膜移植排斥时间 ,A组与B、C、D组、B组与C、D组、C组与D组间两两比较均有显著性差异 (P <0 0 1)。其中作用最强的为C组。结论 :COG滴眼液能有效地防治角膜移植免疫排斥反应。COG滴眼液眼内有效峰浓度出现在点药后 0 986h 。Aim: To observe the pharmacokinetic experiment and effect of the cornus officinalis glycosides (COG) ophthalmic solution on the corneal allograft rejection by topical instillation. Methods: To observe the pharmacokinetic experiment of the cornus officinalis glycosides (COG) eye-drops in the eyes by high performance liquid chromatography (HPLC). The corneal transplantation model on the closed colony rats were set up and then were randomly divided into four groups as follows: group A (blank comparison), group B(0.5% COG), group C(1% COG), group D (2% COG). The rejection time of all animals were recorded and compared by slit-lamp microscope. Results: The aqueous humor concentration time data showed to be subiect to one-compartment model. The concentration aqueous humor-time average equation of rabbit eyes was ρ(t)=10.605×Dose×(e -2.056×(t-0.198)-e -2.579×(t-0.198)), the important parameters: A=4.316 μg/mL,K e=2.056 h -1,K a=2.579 h -1,LagTime=0.198 h,t 1/2,Ka=0.023 h,t 1/2,Ke=0.257 h,T max=0.986 h, ρ max=1.294 μg/mL,AUC=1.601 μg·h/mL. There were statistical difference between group A and B, group A and C, group A and D, group B and C, group B and D, group C and D (P<0.01). Group C was more effective. Conclusion:COG ophthalmic solution has the effect on preventing and suppressing the corneal allograft rejection. The peak concentration of the COG eye-drops is in 0.986 h after dropped, and vanished in 4 h.

关 键 词：实验研究 山茱萸总甙 滴眼液 药代动力学 角膜移植 免疫排斥 

分 类 号：R988.1[医药卫生—药品]