Seiki M, Aita H, Mera Y, Arai K, Toyama S, Furuta S, Morita H, Hori Y, Yoneta T, Tagashira E
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Nihon Yakurigaku Zasshi. 1992 Apr;99(4):255-63. doi: 10.1254/fpj.99.255.
The gastric mucosal adhesiveness of Z-103 in rats with acetic acid ulcer was studied macroscopically, histologically, and biochemically. From macroscopical observations, when Z-103 was orally administered to an acetic acid ulcer model, there was adhesion of Zn to the normal mucosa as well as the ulcerous site under both the fasting condition and after feeding. It was also proven that the strength and duration of adhesiveness were increased dose-dependently under fasting conditions. In addition, histological localization of Zn was noted from the covering epithelial cell layer to the gastric lamina propria mucosae in the normal tissue and in the most superficial ulcerous layer and the granulous layer of the ulcerous site. Measurement of the gastric tissue Zn content after oral administration of 100 mg/kg of Zn showed that the Zn content was significantly increased for 6 hr at the normal site and for 24 hr at the ulcerous site. On the other hand, although ZnSO4 and ZnSO4+carnosine combination macroscopically produced generally the same level of adhesiveness as Z-103, when the gastric tissue Zn content for Z-103 and ZnSO4 were compared, the Zn content of ZnSO4 was lower than that for Z-103 at both the normal and ulcerous site. In summary, Z-103 shows a long-term adhesive and permeable action on the gastric mucosa in acetic acid ulcer rats, and it has a comparable high affinity at the ulcerous site.
对Z - 103在乙酸溃疡大鼠中的胃黏膜黏附性进行了宏观、组织学和生化研究。从宏观观察来看,当给乙酸溃疡模型口服Z - 103时,在禁食状态和进食后,锌在正常黏膜以及溃疡部位均有黏附。还证实,在禁食条件下,黏附强度和持续时间呈剂量依赖性增加。此外,在正常组织中,从覆盖上皮细胞层到胃固有黏膜,以及在溃疡部位的最表层溃疡层和颗粒层均观察到锌的组织学定位。口服100mg/kg锌后对胃组织锌含量的测定表明,正常部位的锌含量在6小时内显著增加,溃疡部位在24小时内显著增加。另一方面,虽然硫酸锌和硫酸锌+肌肽组合在宏观上产生的黏附性与Z - 103大致相同,但比较Z - 103和硫酸锌的胃组织锌含量时,硫酸锌在正常和溃疡部位的锌含量均低于Z - 103。总之,Z - 103对乙酸溃疡大鼠的胃黏膜具有长期的黏附及渗透作用,且在溃疡部位具有相当高的亲和力。