复方核黄素眼用即型凝胶的兔眼内药效学研究

Studying on pharmacodynamics of the compound riboflavin in situ forming eye gel in rabbit eyes

目的 考察复方核黄素眼用即型凝胶的药效作用。方法 在钴蓝光下观察经荧光素纳染色后的复方核黄素眼用即型凝胶在新西兰兔眼表的滞留时间;采用眼刺激评分量表进行评分,考察复方核黄素眼用即型凝胶单次给药后1、24、48和72 h的眼表刺激性及多次给药后第7和14天对眼表造成的累积或持续损害;用0.25%氢氧化钠溶液复制角膜损伤模型,将12只新西兰兔随机分为模型组、滴眼液组和即型凝胶组,模型复制后每组兔右眼分别滴入相应的药物,左眼作为正常空白对照。分别在模型复制后第1、3、5、7天观察兔的眼角膜损伤恢复情况,第7天将兔处死,取角膜组织进行HE染色,观察组织形态学变化,评估药物对角膜损伤恢复的疗效。结果 复方核黄素眼用即型凝胶眼表滞留时间(306.0±33.3)s比滴眼液的眼表滞留时间(9.67±2.52)s长(P<0.05);即型凝胶对兔眼表无刺激性;模型复制成功后,即型凝胶组与模型组比较,损伤恢复状况在第5和第7天差异均有统计学意义(P<0.05);模型复制后第7天,与正常空白对照比较,即型凝胶组和滴眼液组的眼表损伤已逐渐恢复。结论 复方核黄素眼用即型凝胶能延长药物的眼表保留时间,不具有眼部刺激性,可促进角膜损伤恢复。

Objective To study pharmacodynamics of the compound riboflavin in situ forming eye gel.Methods We observed the retention time of compound riboflavin eye gel in New Zealand rabbit’s eye surface after fluorescein staining under cobalt blue light.Eye stimulation scale was used to score and investigate the ocular surface irritation of compound riboflavin in situ forming eye gel for 1 h,24 h,48 h and 72 h after single administration of the in situ eye gel and the cumulative or sustained damage was used to the ocular surface on the 7th day and 14th day after multiple administration of the drug.Corneal injury model was made with 0.25% NaOH solution.Twelve New Zealand rabbits were randomly divided into three groups:model group,eye drops group and in situ eye gel group.The right eye of the rabbits were with the corresponding drug,and the left were used as the blank control.Corneal injury was inspected on the 1st,3rd,5th and 7th day after modeling.The rabbits were sacrificed on the 7th day and the corneal tissue was taken for HE staining.The histomorphologic changes were observed to evaluate the therapeutic effect of drugs on corneal injury recovery.Results The retention time of compound riboflavin ophthalmic in situ gel was (306.0±33.3) s,and that in eye drops was (9.67±2.52) s,which was shorter than the previous one (P<0.05).The in situ eye gel was with no irritation to the rabbit eye surface.After the successful modeling of corneal injury,there were significant differences between the in situ eye gel group and the model group on the 5th day and the 7th day (P<0.05).It was discovered that the ocular surface damage of the type gel group and the eye drops group was gradually recovered on the 7th day after the model was made when compared with blank control group.Conclusion The gel significantly increased the retention time of the drug with no irritation.It is found that compound riboflavin in situ ophthalmic gel can benefit to corneal injury repair.