5-氨基水杨酸温敏凝胶灌肠液的制备及体内外性质考察

Preparation of 5-aminosalicylic Acid Thermosensitive Gel Enema and Its Properties in vivo and in vitro

目的制备5-氨基水杨酸温敏凝胶灌肠液(5-aminosalicylic acid thermosensitive gel enema,5-ASA-TGE),并对其体内外性质进行考察。方法采用冷法工艺制备5-ASA-TGE;通过流变仪检测5-ASA-TGE在不同温度下的流变学参数;采用葡聚糖硫酸钠建立小鼠急性溃疡性结肠炎模型,进行初步药效学研究;以大鼠为受试对象,考察5-ASA-TGE对肠黏膜的刺激性。结果5-ASA-TGE具有良好的温度响应灵敏度,相变温度约为30.3℃;5-氨基水杨酸(5-aminosalicylic acid,5-ASA)采用局部灌肠给药的方法对急性溃疡性结肠炎的小鼠模型有明显的疗效,5-ASA-TGE能有效减少药液泄露,疗效较常规灌肠液更佳;5-ASA-TGE不会对肠黏膜造成刺激和损伤。结论5-ASA-TGE符合肠道局部用药要求,渗漏率低,组织相容性好,具有良好的开发和应用前景。

Objective To prepare 5-aminosalicylic acid thermosensitive gel enema(5-ASA-TGE),and investigate its in vitro and in vivo properties.Methods 5-ASA-TGE was prepared by cold dissolving method.The rheological properties of 5-ASA-TGE during phase transition at different temperature were determined by rotational rheometer.Ulcerative colitis model of mice were applied to assess the in vivo therapeutic effects of 5-ASA-TGE.The stimulation of 5-ASA-TGE to colonic mucosa was studied in rats.Results 5-ASA-TGE had excellent temperature sensitivity and its phase transition temperature was about 30.3℃.The prepared 5-ASA-TGE had remarkable curable effects on animal model through rectal administration,and better efficacy than common mesalazine enema due to the reduce of drug leakage.The excipients of 5-ASA-TGE did not cause irritation and damage to colonic mucosa.Conclusion 5-ASA-TGE with low leakage rate and good histocompatibility meets the design requirement for rectal administration and has broad prospects for development and application.