Seiki M, Ueki S, Tanaka Y, Soeda M, Hori Y, Aita H, Yoneta T, Morita H, Tagashira E, Okabe S
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Nihon Yakurigaku Zasshi. 1990 May;95(5):257-69. doi: 10.1254/fpj.95.5_257.
We investigated the anti-ulcer effects of zinc L-carnosine (Z-103) using several acute experimental models of gastric and duodenal lesions in rats. Effects of Z-103 on various gastric functions, e.g., antacid (in vitro), anti-pepsin (in vitro), gastric secretion, mucosal potential difference (PD) and mucus contents were also examined. Z-103 given orally prevented development of gastric lesions induced by water immersion stress, histamine, HCl-aspirin, HCl-ethanol and also duodenal ulcers induced by mepirizole in a dose-dependent manner. In vitro, Z-103 had a greater antacid effect than sodium bicarbonate; and moreover, the potency of its anti-peptic action (IC50 = 8.7 mM) was higher than those of several other drugs (sodium bicarbonate, sucrose sulfate and aceglutamide aluminum). Intragastric treatment of Z-103 (100 mg/kg alone tended to increase PD, and it also significantly inhibited the decrease in PD induced by aspirin. In addition, pretreatment with Z-103 at 10 and 30 mg/kg (p.o.) significantly prevented the decrease in mucus contents in the gastric mucosa and also mucosal lesions by oral administration of ethanol. On the other hand, Z-103 was not so effective on both basal (pylorus-ligation preparation) and histamine-stimulated gastric secretion (Heidenhain pouch preparation). These results suggest that Z-103 is useful for the treatment of gastric and duodenal ulcers in humans.
我们使用大鼠胃和十二指肠损伤的几种急性实验模型研究了L-肌肽锌（Z-103）的抗溃疡作用。还检测了Z-103对各种胃功能的影响，例如抗酸作用（体外）、抗胃蛋白酶作用（体外）、胃分泌、黏膜电位差（PD）和黏液含量。口服给予Z-103可剂量依赖性地预防由水浸应激、组胺、盐酸-阿司匹林、盐酸-乙醇诱导的胃损伤以及由美吡拉敏诱导的十二指肠溃疡。在体外，Z-103的抗酸作用比碳酸氢钠更强；此外，其抗胃蛋白酶作用的效力（IC50 = 8.7 mM）高于其他几种药物（碳酸氢钠、硫酸蔗糖酯和醋谷胺铝）。胃内给予Z-103（100 mg/kg）单独给药时倾向于增加PD，并且它还显著抑制阿司匹林诱导的PD降低。此外，以10和30 mg/kg（口服）的Z-103预处理可显著预防胃黏膜中黏液含量的降低以及口服乙醇引起的黏膜损伤。另一方面，Z-103对基础（幽门结扎制备）和组胺刺激的胃分泌（海登海因小胃制备）均没有那么有效。这些结果表明Z-103可用于治疗人类的胃和十二指肠溃疡。
