Effects of
NC-1300 (a gastric
proton pump inhibitor) on healing of experimental chronic
gastric ulcers induced in rats were studied.
Gastric ulcers were induced by the submucosal injection of 20%
acetic acid (0.03 ml) into the
antral-oxyntic border of the anterior wall of male Donryu rats (260-280 g). The healing of
acetic acid ulcers was delayed by the daily subcutaneous administration of
indomethacin (1 mg/kg) for two or four weeks after ulceration. Aggravation of healed
ulcers was evoked by subcutaneous administration of
indomethacin (1 mg/kg) once daily for four weeks to rats with four-week-old
ulcers.
Oral administration of
NC-1300 (10, 30, or 100 mg/kg) once daily for two or four weeks after ulceration dose-dependently accelerated both natural and delayed healing of
acetic acid ulcers. When the period of administration was extended from two to four weeks, the ED50 values (the dose reducing the ulcerated area by 50%) were decreased from 36.5 to 13.5 mg/kg in natural healing and from 76.0 to 23.0 mg/kg in delayed healing. Aggravation of four-week-old
ulcers by
indomethacin was significantly prevented by daily administration of
NC-1300 (30 or 100 mg/kg) for four weeks.
Acetic acid ulcers that were healed with
NC-1300 given for four weeks after ulceration remained healed for four to eight weeks after the cessation of
drug administration. A single administration of
NC-1300 to normal rats and repeated administration of
NC-1300 to rats with
acetic acid ulcers for four weeks after ulceration caused the same degree of inhibition of gastric acid secretion.(ABSTRACT TRUNCATED AT 250 WORDS)