| ASKC263(dextrose lansoprazole for injection) is a type of new drug. According to the informations associated with the relevant literature and referring to the GLP standards, we started "ASKC263 pharmacodynamics Experimental Study " aimed to study the effects of ASKC263 on reflux esophagitis model, the model of acute peptic ulcer, chronic peptic ulcer model; using whole stomach of guinea pigs and rats to learn the effects of AKC263 on gastric acid secretion. On the other hand,we studied the effects of ASKC263 on the protective factors peptic ulcer including mucus,free mucus and pepsin. At the same time, compare with(S)-Lansoprazole,(R)-Lansoprazole, and Lansoprazole for injection. The results are summarized as follows: Part I Effects of ASKC263 on reflux esophagitis The result showed that ASKC263 significantly improved acute Acid Reflux esophagitis of rats at doses of 8.1mg /kg; Lansoprazole for injection have significant improvement at a dose of 16.2mg / kg in rats. Dextral and L- lansoprazole for injection have no no significant improvement at a dose of Lansoprazole 2.7,8.1mg / kg. When When the dose is equal, improvement of ASKC263 stronger than the R-lansoprazole(oral formulation) and L- lansoprazole for injection; and other clinical intends to use multiple ASKC263 and lansoprazole for injection on acute Acid Reflux esophagitis the improvement similar. The effects of ASKC263 is similar to Lansoprazole for injection while clinical intented dosages equal. Part II Effects of ASKC263 on acute peptic ulcer The results shows that ASKC263 could significantly reduced the ulcer index of the animal models including Reserpine-induced and Asprin-induced acute gastric ulcer in mice, ethanol-induced, water immersion restraint stress-induced and pyloric ligated acute gastric ulcer in rats, histamine-induced acute gastric ulcer in Guinea pigs at dose of clinical intented dosages,as well as Cysteamine-induced duodenal ulcer. The anti-ulcer effect has obvious dose-effect relationship.(R)-Lansoprazole( oral formulation) and L – lansoprazole for injection also improved above models,However, their sffects are significantly weaker than ASKC263. Lansoprazole for injection has similar effects to ASKC263 while clinical intented dosages is equal. Part III Effects of ASKC263 on chronic peptic ulcer The results showed that,ASKC263 can obviously increase the ulcer index of chronic gastric ulcer model(acetic acid-induced ulcer) and chronic duodenal ulcer model(acetic acid-indced duodenal ulcer) at 1 times the clinical intented dosages.(R)-Lansoprazole( oral formulation) and L – lansoprazole for injection also improved above models,However, their sffects are significantly weaker than ASKC263. Lansoprazole for injection has similar effects to ASKC263 while clinical intented dosages is equal. No significant difference were observed between the two. Part IV Effects of ASKC263 on attack factors and protective factors To confirm whether ASKC263 direct influence the attack factors of peptic ulcer, we detected the secretion of gastric acid and pepsin with normal rats. The results showed that ASKC263 can significantly reduced the gastric acid secretion and stomach protease activity at the dose of 1 times linical intented dosages.(R)-Lansoprazole( oral formulation) and L – lansoprazole for injection also improved above models,However, their effects are significantly weaker than ASKC263. Lansoprazole for injection has similar effects to ASKC263 while is equal. No significant difference were observed between the two. To further confirm whether ASKC263 direct influence the protective factors of peptic ulcer, we detected the secretion of mucus, free mucus and PGE2 with normal rats. The results showed that there is no test substance takes remarkable effects to the protective factors of peptic ulcer. It prompts that ASKC263 protect the stomach by reducing gastric acid secretion, indirectly reduce stomach protease activity, rather than the path that enhancing gastric ulcer protective factors to achieve the purpose. According to the research results, ASKC263 can significant improve reflux esophagitis, acute and chronic gastric ulcer, acute and chronic duodenal ulcers at dose of 1 times and 3 times the clinical intented dosages. At this dose ASKC263 can inhibit gastric acid secretion, and reduce stomach the protease activity, however, there is no significant effect to the secretion of mucus, free mucus and PGE2.When the clinical intented dosages is equal, Lansoprazole for injection has similar effects to ASKC263 while is equal. No significant difference were observed between the two. R-lansoprazole(oral formulation) and L- lansoprazole for injection can also improve eflux esophagitis, acute and chronic gastric ulcer, acute and chronic duodenal ulcers at dose of 1 times and 3 times the clinical intented dosages. But it is significant weaker than ASKC263. In our laboratory conditions, the effects on above drugs with clinical intented dosages is: ASKC263≈Lansoprazole for injection >(R)-Lansoprazole >(S)-Lansoprazol. |
