Sobajima H, Hayakawa T, Kondo T, Shibata T, Kitagawa M, Sakai Y, Ishiguro H, Tanikawa M, Nakae Y
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Pancreas. 1993 Mar;8(2):240-7. doi: 10.1097/00006676-199303000-00016.
The effect of a novel synthetic trypsin inhibitor, 4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate (ONO-3307), on severe acute pancreatitis was studied by changing its timing, frequency, and dose in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of ONO-3307 administration: group A, 2 mg/0.5 ml of ONO-3307 s.c. 1 h before and after induction of pancreatitis; group B, 2 mg/0.5 ml s.c. 1 and 3 h after; group C, 4 mg/1 ml s.c. 1 h before; group D, 4 mg/1 ml s.c. 1 h after. The survival rate at 24 h was significantly improved in group A (75% in A vs. 17% in control; p < 0.01) and in group B (57 vs. 29%; p < 0.05), but not in group C or D. Amylase and immunoreactive trypsin in serum and ascites of the treated were significantly lower than those of controls in both groups A and B. The survival rates were improved dose dependently when ONO-3307 was administered 1 h before and after induction of pancreatitis. ONO-3307 showed favorable effects on the initial stage of severe acute pancreatitis when given in divided doses to maintain the effective serum levels.
通过在大鼠胰蛋白酶-牛磺胆酸盐诱导的急性实验性胰腺炎中改变新型合成胰蛋白酶抑制剂4-氨磺酰基苯基4-胍基苯甲酸甲酯甲磺酸盐（ONO-3307）的给药时间、频率和剂量，研究了其对重症急性胰腺炎的影响。根据ONO-3307给药方式的不同，将大鼠分为四组：A组，在胰腺炎诱导前1小时和诱导后1小时皮下注射2mg/0.5ml ONO-3307；B组，在诱导后1小时和3小时皮下注射2mg/0.5ml；C组，在诱导前1小时皮下注射4mg/1ml；D组，在诱导后1小时皮下注射4mg/1ml。A组（A组24小时存活率为75%，对照组为17%；p<0.01）和B组（57%对29%；p<0.05）24小时存活率显著提高，但C组和D组未提高。A组和B组治疗组血清和腹水中的淀粉酶和免疫反应性胰蛋白酶均显著低于对照组。在胰腺炎诱导前1小时和诱导后1小时给予ONO-3307时，存活率呈剂量依赖性提高。当分剂量给予ONO-3307以维持有效血清水平时，其对重症急性胰腺炎的初始阶段显示出良好的效果。
