Crystal of quinoline derivative

Abstract

Crystals of [8-chloro-3-(4-chlorobenzyl)-4-difluoromethoxy-2-ethylquinolin-5-yloxy]acetic acid L-lysine salt, i.e., a crystal A which has peaks at diffraction angles 2θ=6.0°, 10.0°, 10.7°, 12.1°, 18.4°, 19.2° and 20.1° in powder X-ray diffraction spectra and a crystal B which has peaks at diffraction angles 2θ=6.0°, 11.7°, 12.4°, 15.2°, 16.4°, 20.3° and 22.6° in powder X-ray diffraction spectra. These crystals are chemically stable and have excellent thermal stability and physical properties, and are therefore suitable as medicinal substances.

1 . Crystals of [8-chloro-3-(4-chlorobenzyl)-4-difluoro-methoxy-2-ethylquinolin-5-yloxy]acetic acid L-lysine salt. 
     
     
         2 . The crystals as claimed in  claim 1 , which are crystals A. 
     
     
         3 . The crystals as claimed in  claim 1 , which, in their powder X-ray diffraction spectrum, have peaks at diffraction angles 2θ=6.0°, 10.0°, 10.7°, 12.1°, 18.4°, 19.2°, and 20.1°. 
     
     
         4 . The crystals as claimed in  claim 1 , which have the powder X-ray diffraction spectrum pattern shown in  FIG. 1 . 
     
     
         5 . The crystals as claimed in  claim 1 , which, in their infrared absorption spectrum, have absorption peaks at wavenumbers 673 cm −1 , 810 cm −1 , 872 cm −1 , 1010 cm −1 , 1051 cm −1 , 1413 cm −1 , and 1568 cm −1 . 
     
     
         6 . The crystals as claimed in  claim 1 , which have the infrared absorption spectrum pattern shown in  FIG. 3 . 
     
     
         7 . The crystals as claimed in  claim 1 , which, in their solid-state  13 C-NMR spectrum, have chemical shift peaks at 107.1 ppm, 115.9 ppm, 127.5 ppm, 136.5 ppm, 145.7 ppm, 152.7 ppm, 153.8 ppm, 165.8 ppm, 175.8 ppm, 177.3 ppm, and 179.5 ppm. 
     
     
         8 . The crystals as claimed in  claim 1 , which have the solid-state  13 C-NMR spectrum pattern shown in  FIG. 5 . 
     
     
         9 . The crystals as claimed in  claim 1 , which, in their solid-state  19 F-NMR spectrum, have chemical shift peaks at −77.0 ppm, and −72.3 ppm. 
     
     
         10 . The crystals as claimed in  claim 1 , which have the solid-state  19 F-NMR spectrum pattern shown in  FIG. 6 . 
     
     
         11 . The crystals as claimed in  claim 1 , which, in their solid-state  15 N-NMR spectrum, have a chemical shift peak at −347.2 ppm. 
     
     
         12 . The crystals as claimed in  claim 1 , which have the solid-state  15 N-NMR spectrum pattern shown in  FIG. 7 . 
     
     
         13 . The crystals as claimed in  claim 1 , which are crystals B. 
     
     
         14 . The crystals as claimed in  claim 1 , which, in their powder X-ray diffraction spectrum, have peaks at diffraction angles 2θ=6.0°, 11.7°, 12.4°, 15.2°, 16.4°, 20.3°, and 22.6°. 
     
     
         15 . The crystals as claimed in  claim 1 , which have the powder X-ray diffraction spectrum pattern shown in  FIG. 2 . 
     
     
         16 . The crystals as claimed in  claim 1 , which, in their infrared absorption spectrum, have absorption peaks at wavenumbers 667 cm −1 , 803 cm −1 , 885 cm −1 , 1012 cm −1 , 1032 cm −1 , 1402 cm −1 , and 1597 cm −1 . 
     
     
         17 . The crystals as claimed in  claim 1 , which have the infrared absorption spectrum pattern shown in  FIG. 4 . 
     
     
         18 . A pharmaceutical composition containing the crystals as claimed in any of  claims 1 - 17  and pharmaceutically acceptable carrier. 
     
     
         19 . A CRTH2 antagonist containing, as active ingredient, the crystals as claimed in any of  claims 1 - 17 . 
     
     
         20 . A therapeutic drug or preventive drug for one or more diseases chosen from the group consisting of bronchial asthma, chronic obstructive pulmonary disease, bronchitis, cystic fibrosis, perennial allergic rhinitis, seasonal allergic rhinitis, chronic eosinophilic rhinosinusitis, and chronic noneosinophilic rhinosinusitis, containing, as active ingredient, the crystals as claimed in any of  claims 1 - 17 . 
     
     
         21 . A therapeutic drug or preventive drug for one or more diseases chosen from the group consisting of psoriasis, atopic and nonatopic dermatitis, chronic spontaneous urticaria, Crohn's disease, ulcerative colitis, eosinophilic gastrointestinal disease, and irritable bowel disease, containing, as active ingredient, the crystals as claimed in any of  claims 1 - 17 .