α-取代的对甲磺酰基苯丙烯酸的抗炎活性及对胃肠道影响的实验研究  

A Experimental Study on the Anti-inflammatory Activity and Gast rointestinal Lesions of α-Substituted p-Methylsulfonylphenylpropeno ic Acids

作　　者：邓钢[1] 季晖[1] 张奕华[2] 敖桂珍[2] 蔡曼玲[1] 冯晓春[1] 

机构地区：[1]中国药科大学药理学教研室,江苏南京210009 [2]中国药科大学新药研究中心,江苏南京210009

出　　处：《药学进展》2003年第2期103-107,共5页Progress in Pharmaceutical Sciences

摘　　要：[目的 ]对 1 7个目标化合物———α 取代的对甲磺酰基苯丙烯酸进行抗炎活性初筛 ,并考察其中活性化合物对大鼠胃肠道的影响。 [方法 ]以双氯芬酸和罗非昔布作为阳性对照药 ,首先采用小鼠耳二甲苯致炎模型对所有目标化合物进行抗炎活性初筛 ;随后采用角叉菜胶致大鼠足跖肿胀模型对其中活性化合物继续进行抗炎活性筛选 ;选用活性化合物给大鼠连续灌胃 7天 ,并于末次给药后观察并比较其对大鼠胃肠道的影响。 [结果 ]目标化合物ZA1 、ZA3、ZA7、ZA9、ZA1 0 、ZA1 3、ZA1 5、ZA1 6 均能抑制二甲苯所致小鼠耳肿胀 ;其中ZA1 、ZA1 3、ZA1 5能明显减轻大鼠足跖肿胀 ,且ZA1 3、ZA1 5与罗非昔布相比无显著差异 (P >0 .0 5) ;大鼠胃、十二指肠溃疡面积测定结果发现 ,所有受试药物中罗非昔布、ZA7、ZA9、ZA1 0 、ZA1 3、ZA1 5的胃肠道副作用小于双氯芬酸 (P <0 .0 5) ,其中ZA1 0 、ZA1 5与羧甲基纤维素钠相比无显著差异 (P >0 .0 5) ,ZA1 0 与罗非昔布无明显差异 (P >0 .0 5)。 [结论 ]目标化合物ZA1 3、ZA1 5值得进一步研究。AIM] To search for target com pounds with stronger anti-inflammatory activity and less gastro intestinal(GI) l esions. [METHODS]Diclofenac and rofecoxib were used as positiv e control. Two models were introduced to evaluate the anti-inflammatory activity of 17 target compounds——α-substituted \%p\%-methylsulfonylphenylpropenoic acid s , one is xylene-induced mouse ear swelling , the other is carrageenan-induce d rat paw edema . The GI lesions associated with them in the rats were examined. [RESULTS] Compounds ZA 1, ZA 3, ZA 7, ZA 9, ZA 10 , ZA 13 , ZA 15 and ZA 16 exhibited remarkable inflammatory activity in xylene-induced mouse ear swelling model. And they were further evaluated in car rageenan-induced rat paw edema model. Compounds ZA 1, ZA 13 and ZA 15 showed inflammatory activity comparable to vehicle control. No significan t difference between ZA\-\{13\} and ZA\-\{15\} and rofecoxib was found. Most of the compound s with anti-inflammatory activity induced less GI lesions than diclofenac, but a li ttle more than rofecoxib. [CONCLUSION] Target compounds ZA 1 3 and ZA 15 deserve further study.

关 键 词：非甾体抗炎药 胃肠道反应 COX-2选择性抑制剂 对甲磺酰基苯丙烯酸 α-取代 抗炎活性 

分 类 号：R96[医药卫生—药理学]