离体圆窗膜对地塞米松不同制剂的通透性  

Permeability of different Dexamethasone drugs through round window membrane

作　　者：刘娅[1] 孙建军[1] 孔维佳[2] 江平[1] 姜伟[1] 

机构地区：[1]海军总医院全军耳鼻咽喉科中心,北京100037 [2]华中科技大学同济医学院附属协和医院耳鼻咽喉科

出　　处：《中华耳鼻咽喉头颈外科杂志》2006年第3期211-215,共5页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：首都医学发展基金资助项目(2002-2012)

摘　　要：目的制备离体圆窗膜试验模型,分析海藻酸钠(alginate sodium,ALG)、羧甲基甲壳胺(carboxymethyled chitosan,CHI)2种缓释剂对地塞米松(dexamethasone,DXM)透膜释放的效力。方法模拟中耳及外淋巴腔环境,设计圆窗膜离体试验模型;制备不同浓度的海藻酸钠和羧甲基甲壳胺的地塞米松磷酸钠组。利用圆窗膜离体试验模型,于9h内的不同时间点采样,用高效液相色谱(high performance liquid chromatography,HPLC)法测定浓度,计算地塞米松对圆窗膜的累积通透量并进行方程模拟。结果对照组在给药后3h内迅速通透圆窗膜,3h后接近平衡;25g/L海藻酸钠分别与4g/L或6g/L羧甲基甲壳胺的配方缓释作用最强(P<0·01);单独应用25g/L海藻酸钠的缓释作用次之;单独应用4g/L羧甲基甲壳胺仅具有微小促渗作用。结论离体圆窗膜通透模型允许地塞米松分子自由通透;添加合适剂量的缓释材料———海藻酸钠与羧甲基甲壳胺的地塞米松磷酸钠制剂具有明显缓释作用,有可能成为未来用于内耳局部给药缓释材料的理想选择。Objective To analysis the effect of sustained delivering two adjuncts alginate sodium （ALG） and carboxymethyled chitnsan（CHI） on permeating of dexamethasone （ DXM ） through experimental apparatus to round window membrane. Methods The experimental apparatus for round window membrane in vitro was designed by simulating the environment of middle ear and scala tympani. Different drugs of DXM sodium included variable concentrations of ALG and CHI were prepared. Using the experimental apparatus, DXM permeating from round window membrane was sampled in 9 hours while its quantities were measured with high performance liquid chromatography, and then different pharmaceutical equations were simulated. Results The releasing quantity of control group （without any adjuncts） rose rapidly within 3 hours, and then approximated to balance. ALG （25 g/L） ＋CHI（4 g/L） or ALG（2.5 g/L） ＋ CHI（6 g/L） showed the great effect of sustained release, but ALG （ 25 g/L） alone took the second place. CHI （ 4 g/L） alone enhanced the transmembranons permeability. Conclusious With the in vitro apparatus, DXM could permeate through the round window membrane. DXM added with appropriate component of ALG and CHI could be good drugs for sustained release.

关 键 词：地塞米松 色谱法 高压液相 体外研究 圆窗 

分 类 号：R764[医药卫生—耳鼻咽喉科]