生物黏附性眼用双氯芬酸温度敏感水凝胶研究

Study of Diclofenac Temperature Sensitive Hydrogel with Bioadhesive Eye

目的:采用生物黏附技术、应用泊洛沙姆联合复合羧甲基化壳聚糖制备一种新型的眼用双氯芬酸温度敏感水凝胶,考察其体内药动学作用。方法:选用泊洛沙姆、羧甲基壳聚糖和双氯芬酸共同制备双氯芬酸水溶液及水凝胶,分别应用于成年健康家兔的左右眼,并观察两种制剂的眼表滞留时间、体内药动学变化及水凝胶的流变学变化。结果:双氯芬酸水凝胶有眼部适用性、安全性和温度敏感性,凝胶转变温度为24℃左右,转变温度与羧甲基壳聚糖或双氯芬酸无明显相关性。双氯芬酸荧光素钠水凝胶的黏附力强,眼表滞留时间较水溶液更长。在整个用药过程中,水凝胶的药物浓度在各个时间点均高于水溶液,两种制剂均于用药后45min达到药物浓度的峰值,水凝胶为5.76g/L,水溶液为2.5g/L。结论:用该方法制备的双氯芬酸温度敏感水凝胶具有较好的眼部适用性和安全性,用药后可根据眼部生理温度逐渐由液态转变为凝胶状态,延长药物的眼表滞留时间以提高药物生物利用度。

Objective： The biological adhesion,application of poloxamer combined with carboxymethyl chitosan to prepare a new kind of temperature sensitive hydrogel ophthalmic diclofenac,study its pharmacokinetic effect.Methods：Using poloxamer,carboxymethyl chitosan and diclofenac preparation of diclofenac solution and hydrogel,adult healthy rabbits were applied to the left eye,and to observe the eye two formulations of retention time,the pharmacokinetic changes in rheological changes and hydrogel. Results：Diclofenac hydrogels have eye applicability,safety and sensitivity to temperature,gel transition temperature is 24℃,there was no significant correlation between transition temperature and carboxymethyl chitosan or diclofenac.Adhesion of diclofenac sodium fluorescein hydrogel,ocular retention time longer than water solution.In the whole process of drug,drug concentration hydrogel were higher than that of water solution at each time point,peak two preparations were on medication after 45 min to the drug concentration,the hydrogel is 5.76g/L,2.5g/L water solution.Conclusion：Diclofenac temperature sensitive hydrogel prepared by the method has the eye for better efficacy and safety,the drug can be according to the eye physiological temperature gradually changed from liquid to gel state table,extend eye drug retention time in order to improve the bioavailability of drugs.