Tetomilast Polymorphs

Abstract

The present invention provides a tetomilast crystal that is industrially easily produced in a large volume. (1) a tetomilast hydrate crystal having a power X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG. 2 ; (2) an anhydrous tetomilast type A crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG. 4 ; (3) an anhydrous tetomilast type C crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG. 8 ; (4) a tetomilast acetonitrile solvate crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in FIG. 10 ; and (5) a mixture consisting of the above anhydrous tetomilast type A crystal and an anhydrous tetomilast type B crystal. These crystals are stable towards heat and moisture, and are also excellent in terms of the disintegration property and dissolution property of tablets. Accordingly, these crystals are preferably used as pharmaceutical compositions.

1 . A method of treating gastrointestinal ulcer, cardiacischemic disease, cerebrovascular disease, a liver and kidney function improver used for disorders caused by transplantation, microcirculation failure, etc., or Behcet's disease, cutaneous vasculitis, ulcerative colitis, malignant rheumatism, arthritis, arteriosclerosis or diabetes which comprises administering to a patient in need thereof an effective amount of anhydrous tetomilast type A crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in  FIG. 4 , or having a powder X-ray diffraction spectrum having characteristic peaks at 2Θ=10.5°, 13.1°, 18.4°, 21.9°, and 25.8°. 
     
     
         2 . A method of treating chronic rheumatoid arthritis, endotoxin shock, ARDS, thermal burn, asthma, chronic heart failure, myocardial infarction, viral myocarditis, or treating ischemic reperfusion abnormality, transition from SIRS (systemic inflammatory response syndrome) to organ failure, multiple organ failure, inflammatory bowel disease, autoimmune disease, metastasis, immunological rejection occurring during transplantation, monoclonal B cell abnormality, polyclonal B cell abnormality, atrial myxoma, Castleman's syndrome, primary glomerulonephritis, mesangial proliferative nephritis, cancer cachexia, Lennert's lymphoma, psoriasis, atopic dermatitis, Kaposi's sarcoma developed due to AIDS, postmenopausal osteoporosis, septicemia, inflammatory disease which comprises administering to a patient in need thereof, an effective amount of anhydrous tetomilast type A crystal having a powder X-ray diffraction spectrum that is substantially the same as the powder X-ray diffraction spectrum shown in  FIG. 4 , or
 having a powder X-ray diffraction spectrum having characteristic peaks at 2Θ=10.5°, 13.1°, 18.4°, 21.9°, and 25.8°.   
     
     
         3 . The method according to  claim 2 , wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. 
     
     
         4 . The method according to  claim 2 , for treating chronic obstructive pulmonary disease.