pH敏感型魟鱼软骨多糖眼用原位凝胶兔眼药动学及其抑制角膜新生血管的研究  

The ocular pharmacokinetics of ray cartilage glycosaminoglycans(RCG) pH-sensitive in situ ophthalmic gel in rabbits and its inhibition effects against corneal neovascularization

作　　者：赵榛榛 郭斌 韩冠英 

机构地区：[1]锦州医科大学药学院,辽宁锦州121000 [2]锦州医科大学附属第一医院,辽宁锦州121000

出　　处：《中国医院药学杂志》2017年第18期1797-1801,1807,共6页Chinese Journal of Hospital Pharmacy

基　　金：辽宁省科技厅科技攻关计划基金资助项目(编号:2013225305)

摘　　要：目的:制备pH敏感型魟鱼软骨多糖眼用原位凝胶剂(RCG凝胶)并考察其兔眼药动学和抑制角膜新生血管作用。方法:以卡波姆940和HPMC(1∶4,w/w)为辅料制得pH敏感型原位凝胶。取健康家兔30只,向兔眼中滴入50μL RCG凝胶,分别于给药10,30,60,120,180 min后处死家兔,收集兔眼玻璃体、房水、角膜和虹膜,并测定药物含量。取家兔20只,建立角膜新生血管模型并随机分为4组,分别给予生理盐水,25,50,100 mg·mL^(-1) RCG凝胶。观察给药后第3,6,9,12天新生血管面积及角膜病理切片。结果:魟鱼软骨多糖在玻璃体、房水、角膜和虹膜的药动学均符合二室模型,在玻璃体、房水、角膜和虹膜中的Cmax分别为(1.35±0.41),(9.31±0.39),(27.78±0.32),(15.97±0.13)μg·mL^(-1);AUC0-180分别为(80.54±9.65),(571.91±18.32),(1 763.72±48.66),(1 034.55±33.87)μg·mL^(-1)·min。对照组、低、中、高剂量组在第12天的新生血管面积分别为(30.00±3.45),(24.31±3.12),(5.36±1.24),(4.89±1.09)mm2。角膜病理切片中,对照组和低剂量组中有大量炎性细胞浸润,新生血管较多;而中剂量和高剂量组中角膜中炎性细胞和新生血管明显较少。结论:制备了一种pH敏感型魟鱼软骨多糖眼用原位凝胶,该凝胶给药后在角膜部位具有最大的药物浓度,其给药剂量高于50 mg·mL^(-1)时,具有显著的抑制新生血管生成的作用,该原位凝胶剂具有较好的临床应用价值。OBJECTIVE To prepare the ray cartilage glycosaminoglycans（RCG）pH-sensitive in situ ophthalmic gel（RCG gel）,and study the ocular pharmacokinetics in rabbits as well as the inhibition effects against corneal neovascularization.METHODS The pH-sensitive in situ ophthalmic gel was prepared by carbomer 940 and HPMC.Thirty healthy rabbits were administered 50μL RCG gel.The rabbits were sacrificed after 10,30,60,120 and 180 min.The vitreous,aqueous humor,cornea and iris of rabbits were collected and the concentrations of RCG were determined.Twenty rabbits with corneal neovascularization（CNV）were randomly divided into 4 groups.Each group of rabbits were respectively administered saline,25 mg·mL^-1 RCG gel,50 mg·mL^-1 RCG gel and 100 mg·mL^-1 RCG gel.After 3,6,9 and 12 days,the areas of CNV were recorded.The pathological section of cornea was observed after 12 day.RESULTS The pharmacokinetics of RCG in the vitreous,aqueous humor,cornea and iris of rabbits belonged to two-compartment model.The Cmaxvalues of RCG were（1.35±0.41）,（9.31±0.39）,（27.78±0.32）and（15.97±0.13）μg·mL^-1 in the vitreous,aqueous humor,cornea and iris,respectively.The AUC0-180 values of RCG were（80.54±9.65）,（571.91±18.32）,（1 763.72±48.66）and（1 034.55±33.87）μg·mL^-1min in the vitreous,aqueous humor,cornea and iris,respectively.The areas of CNV were（30.00±3.45）,（24.31±3.12）,（5.36±1.24）and（4.89±1.09）mm^2 in control group,low dose group（25 mg·mL^-1）,medium dose group（50 mg·mL^-1）,high dose group（100 mg·mL^-1）,respectively.The pathological section of cornea was observed,inflammatory cell infiltration and new vessels were observed in control group and low dosage group.The inflammatory cell infiltration and new vessels were limited in the medium dose group and high dose group.CONCLUSION A RCG pH-sensitive in situ ophthalmic gel is prepared in this study.After administration,the maximum RCG concentration is found in the cornea.The gel has a significant inhibition against

关 键 词：魟鱼软骨多糖 pH敏感型眼用原位凝胶剂 药动学 方法学 角膜新生血管 

分 类 号：R94[医药卫生—药剂学]