Acid addition salts of benzimidazole derivative
The present invention relates to a pidolate salt and malate salt of a compound represented by a formula 1 with an excellent liquid-phase stability, solid-phase stability, water solubility, precipitation stability and hygroscopicity all together as a compound for preventing and treating diseases mediated by an acid pump antagonistic activity, as well as a method for preparing the same.
1. A pidolate salt or malate salt of a compound represented by a following Formula 1:
2. The salt according to claim 1 , wherein the pidolate salt is a salt represented by a following Formula 2:
3. The salt according to claim 1 , wherein the malate salt is a salt represented by a following Formula 3:
4. The salt according to claim 1 , wherein the salt is noncrystalline.
5. The salt according to claim 1 , wherein the salt is partially crystalline.
6. A pharmaceutical composition for treating diseases mediated by an acid pump antagonistic activity, wherein the pharmaceutical composition comprises a salt according to claim 1 .
7. The pharmaceutical composition according to claim 6 , wherein the diseases mediated by an acid pump antagonistic activity are one selected from the group consisting of a gastroesophageal diseases, a gastroesophageal reflux disease (GERD), a peptic ulcer, a gastric ulcer and a duodenal ulcer, an ulcer induced by NSAID, a gastritis, a Helicobacter pylori infection, a dyspepsia and a functional dyspepsia, Zollinger-Ellison syndrome, a nonerosive reflux disease (NERD), a visceral pain, a purosis, a nausea, an esophagitis, a dysphagia, a salivation, an airway lesion and an asthma.
8. The pharmaceutical composition according to claim 6 , wherein a formulation of the composition is one selected from the group consisting of powder, granule, tablet, capsule, suspension, emulsion, syrup, aerosol, ointment, cream, suppository and injection.
9. A method for preparing a salt of claim 1 , the method comprising:
a) dissolving a compound represented by a following Formula 1 and a pyroglutamic acid or a malic acid in an organic solvent;
b) concentrating a solution prepared in the step a) under decompression to precipitate a solid and then adding a co-solvent thereto to stir a resulting solution; and
c) filtering out and drying a precipitated solid:
10. The method according to claim 9 , wherein the organic solvent of the step a) is methanol and added by 10 times (volume/weight) compared to a compound represented by the Formula 1.
11. The method according to claim 9 , wherein the co-solvent of the step b) may be a mixed solution of acetone and ethyl acetate and is added by 5 times (volume/weight) compared to a compound represented by the Formula 1.
12. The method according to claim 11 , wherein a ratio of the co-solvent is acetone:ethyl acetate=1:4 (v/v).
13. A method for treating a disease mediated by an acid pump antagonistic activity, the method comprising: administrating a therapeutically effective amount of a salt according to claim 1 to a patient in need thereof, wherein the disease mediated by an acid pump antagonistic activity is selected from the group consisting of a gastroesophageal diseases, a gastroesophageal reflux disease (GERD), a peptic ulcer, a gastric ulcer and a duodenal ulcer, an ulcer induced by NSAID, a gastritis, a Helicobacter pylori infection, a dyspepsia and a functional dyspepsia, Zollinger-Ellison syndrome, a nonerosive reflux disease (NERD), a visceral pain, a purosis, a nausea, an esophagitis, a dysphagia, a salivation, an airway lesion and an asthma.