通过研究BX661A对葡聚糖硫酸钠诱导的大鼠溃疡性结肠炎的治疗效果来确定其活性部分，BX661A是一种用于治疗溃疡性结肠炎的新型治疗药物。

Determination of the active moiety of BX661A, a new therapeutic agent for ulcerative colitis, by studying its therapeutic effects on ulcerative colitis induced by dextran sulfate sodium in rats.

作者信息

Kimura I, Kawasaki M, Nagahama S, Matsuda A, Kataoka M, Kokuba Y

机构信息

Infusion Research Department, Hoechst Marion Roussel Ltd., Saitama, Japan.

出版信息

Arzneimittelforschung. 1998 Nov;48(11):1091-6.

PMID:9850431

Abstract

5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is being developed as a therapeutic drug for ulcerative colitis. To determine the active therapeutic moiety of BX661A, the therapeutic effects with single and combined administration of 5-aminosalicylic acid (5-ASA), 4-aminobenzoyl-beta-alanine (4-ABA) and 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP) on ulcerative colitis induced by dextran sulfate sodium (DSS) in rats were investigated, and the following results were obtained. 1. BX661A at doses of 30, 100 and 300 mg/kg (p.o.) dose-dependently decreased the erosion area (mm2) in the large intestine with % inhibition values of 28.7, 49.1 and 61.6%, and the shortening of the large intestine with % inhibition values of 17.1, 25.7 and 48.6%, respectively. Salazosulfapyridine (SASP) at doses of 30 and 100 mg/kg (p.o.) decreased the erosion area (mm2) in the large intestine with % inhibition values of 30.7 and 45.3%, respectively, but did not improve the shortening of the large intestine. However, at a dose of 300 mg/kg (p.o.) SASP, the % inhibition value of the erosion area in the large intestine was reduced. 2. A single intrarectal administration of 5-ASA (105 mg/kg, i.r.) significantly decreased the erosion area (mm2) in the large intestine, but a single administration of 4-ABA or SP did not show any significant effect on the erosion area. Combined administration with 5-ASA (105 mg/kg, i.r.) and 4-ABA (142.8 mg/kg, i.r.) significantly decreased the erosion area (mm2) in the large intestine with a % inhibition value of 63.8%. On the other hand, the efficacy of 5-ASA disappeared with combined administration with SP (% inhibition value of 7.3%). These results suggest that 5-ASA is the active moiety for the therapeutic effects of BX661A and indicate that the efficacy of 5-ASA disappears with the combined use of SP, but not of 4-ABA. Therefore, it seems that BX661A is clinically safe and more effective than SASP in the treatment of patients with ulcerative colitis.

摘要

5-[4-(2-羧乙基氨基甲酰基)苯基偶氮]水杨酸二钠盐二水合物（CAS 80573-04-2，BX661A）正被开发用作治疗溃疡性结肠炎的药物。为确定BX661A的活性治疗部分，研究了5-氨基水杨酸（5-ASA）、4-氨基苯甲酰-β-丙氨酸（4-ABA）和4-氨基-N-2-吡啶基苯磺酰胺（CAS 144-83-2，磺胺吡啶，SP）单独及联合给药对葡聚糖硫酸钠（DSS）诱导的大鼠溃疡性结肠炎的治疗效果，结果如下。1. BX661A剂量为30、100和300 mg/kg（口服）时，大肠糜烂面积（mm²）呈剂量依赖性降低，抑制率分别为28.7%、49.1%和61.6%，大肠缩短的抑制率分别为17.1%、25.7%和48.6%。柳氮磺胺吡啶（SASP）剂量为30和100 mg/kg（口服）时，大肠糜烂面积（mm²）降低，抑制率分别为30.7%和45.3%，但未改善大肠缩短情况。然而，SASP剂量为300 mg/kg（口服）时，大肠糜烂面积的抑制率降低。2. 单次直肠内给予5-ASA（105 mg/kg，直肠内给药）可显著降低大肠糜烂面积（mm²），但单次给予4-ABA或SP对糜烂面积无显著影响。联合给予5-ASA（105 mg/kg，直肠内给药）和4-ABA（142.8 mg/kg，直肠内给药）可显著降低大肠糜烂面积（mm²），抑制率为63.8%。另一方面，5-ASA与SP联合给药时疗效消失（抑制率为7.3%）。这些结果表明5-ASA是BX661A治疗作用的活性部分，表明5-ASA与SP联合使用时疗效消失，但与4-ABA联合使用时并非如此。因此，在治疗溃疡性结肠炎患者时，BX661A似乎比SASP临床安全性更高且更有效。