Claims for Patent: 9,527,833

Summary for Patent: 9,527,833

Title:	Stable crystal form of tipiracil hydrochloride and crystallization method for the same
Abstract:	An objective of the present invention is to obtain a stable crystal form of 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride. The present invention provides a crystal of 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride exhibiting characteristic peaks at angles of 11.6.degree., 17.2.degree., 17.8.degree., 23.3.degree., 27.1.degree., and 29.3.degree. as a diffraction angle (2.theta..+-.0.1.degree.) in powder X-ray diffraction.
Inventor(s):	Kazuno; Hideki (Ibaraki, JP), Mutsumi; Tomonobu (Saitama, JP)
Assignee:	TAIHO PHARMACEUTICAL CO., LTD. (Tokyo, JP)
Application Number:	14/896,748
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,527,833
Patent Claims:	1. A crystal of 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, which is crystal Form I, exhibiting peaks at two or more angles selected from the group consisting of 11.6.degree., 17.2.degree., 17.8.degree., 23.3.degree., 27.1.degree., and 29.3.degree. as a diffraction angle (2.theta..+-.0.1.degree.) in powder X-ray diffraction. 2. The crystal according to claim 1, exhibiting peaks at angles of 11.6.degree., 17.2.degree., 17.8.degree., 23.3.degree., 27.1.degree., and 29.3.degree. as a diffraction angle (2.theta..+-.0.1.degree.) in powder X-ray diffraction. 3. The crystal according to claim 1, exhibiting an endothermic peak determined by thermogravimetry-differential thermal analysis at a temperature of around 262.degree. C. 4. The crystal according to claim 1, which shows, in single-crystal analysis, the following crystal data: Crystal system: monoclinic system Space group: P2.sub.1/n (No. 14) Lattice constant: a=11.6006 (9) .ANG. b=10.3106 (11) .ANG. c=10.3036 (10) .ANG. .alpha.=90.degree. .beta.=101.951 (7).degree. .gamma.=90.degree. Unit lattice volume: 1205.7 (2) .ANG..sup.3. 5. The crystal according to claim 1, in an anhydrous form. 6. The crystal according to claim 1, having a purity of 90% by mass or more. 7. The crystal according to claim 1, exhibiting peaks at two or more angles selected from the group consisting of 11.6.degree., 17.2.degree., 17.8.degree., 23.3.degree., 27.1.degree., and 29.3.degree. as a diffraction angle (2.theta..+-.0.1.degree.) in powder X-ray diffraction after a 6-month preservation at 40.degree. C. in a stability test. 8. A pharmaceutical composition comprising the crystal according to claim 1 and a pharmaceutically acceptable carrier. 9. A production method of the crystal according to claim 1, comprising, dissolving 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride in a water-ethanol mixed solvent with heating, and subjecting the solution to crystallization at a temperature of 40.degree. C. or higher, followed by cooling.