Details for Patent: 8,981,103

Title:	Stable crystal of 4-oxoquinoline compound
Abstract:	Provision of a stabilized crystal of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-meth- oxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound A). A crystal of compound A, which shows a particular X-ray powder diffraction pattern of a characteristic diffraction peaks at diffraction angles 2.theta.(.degree.) as measured by X-ray powder diffractometry.
Inventor(s):	Ando; Koji (Osaka, JP), Matsuda; Koji (Osaka, JP), Miyake; Shuji (Osaka, JP), Uehara; Hideto (Osaka, JP)
Assignee:	Japan Tobacco Inc. (Tokyo, JP)
Filing Date:	Aug 10, 2009
Application Number:	12/538,694
Claims:	1. A crystal form of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-meth- oxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, having an X-ray powder diffraction pattern comprising a characteristic diffraction peak at 8.54.+-.0.2.degree. .crclbar.. 2. The crystal form of claim 1, having an X-ray powder diffraction pattern comprising a characteristic diffraction peak at 8.54.+-.0.1.degree. 2.crclbar.. 3. The crystal form of claim 1, having an X-ray powder diffraction pattern comprising a characteristic diffraction peak at 8.54.+-.0.06.degree. 2.crclbar.. 4. The crystal form of claim 1, having an X-ray powder diffraction pattern further comprising a characteristic diffraction peak at 17.24.degree..+-.0.2.degree. 2.crclbar.. 5. The crystal form of claim 2, having an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 8.54.+-.0.1.degree. and 17.24.degree..+-.0.1.degree. 2.crclbar.. 6. The crystal form of claim 3, having an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 8.54.+-.0.06.degree. and 17.24.degree..+-.0.06.degree. 2.crclbar.. 7. The crystal form of claim 4, having an X-ray powder diffraction pattern further comprising a characteristic diffraction peak at 14.02.+-.0.2.degree., 2.crclbar.. 8. The crystal form of claim 5, having an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 8.54.+-.0.1.degree., 14.02.+-.0.1.degree., and 17.24.+-.0.1.degree. 2.crclbar.. 9. The crystal form of claim 7, having an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 8.54.+-.0.06.degree., 14.02.+-.0.06.degree., and 17.24.+-.0.06.degree. 2.crclbar.. 10. A crystal form of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-meth- oxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid having an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 8.54.+-.0.2.degree., 14.02.+-.0.2.degree., 15.8.+-.0.2.degree., 17.06.+-.0.2.degree., 17.24.+-.0.2.degree., 24.16.+-.0.2.degree., and 25.74.+-.0.2.degree. 2.crclbar.. 11. The crystal form of claim 10, having an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 8.54.+-.0.1.degree., 14.02.+-.0.1.degree., 15.68.+-.0.1.degree., 17.24.+-.0.1.degree., 24.16.+-.0.1.degree., and 25.74.+-.0.1.degree. 2.crclbar.. 12. The crystal form of claim 10, having an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 8.54.+-.0.06.degree., 14.02.+-.0.06.degree., 15.68.+-.0.06.degree., 17.06.+-.0.06.degree., 17.24.+-.0.06.degree., 24.16.+-.0.06.degree., and 25.74.+-.0.06.degree. 2.crclbar.. 13. Crystal form III of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-meth- oxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid having an X-ray powder diffraction pattern as shown in FIG. 1. 14. The crystal form of any one of claims 1 and 2 to 13 having a purity of crystal of not less than 70%. 15. The crystal form of any one of claims 1 and 2 to 13 having a purity of crystal of not less than 80%. 16. The crystal form of any one of claims 1 and 2 to 13 having a purity of crystal of not less than 90%. 17. The crystal form of any one of claims 1 and 2 to 13 having a purity of crystal of not less than 95%. 18. The crystal form of any one of claims 1 and 2 to 13 having a purity of crystal of not less than 98%. 19. A pharmaceutical composition comprising the crystal form of any one of claims 1 and 2 to 13 and a pharmaceutically acceptable carrier. 20. The pharmaceutical comppsition of claim 19 wherein the composition is in the form of a tablet, pill, powder or granule.