Claims for Patent: 10,821,108

Summary for Patent: 10,821,108

Title:	Pharmaceutical composition containing 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide
Abstract:	A stabilized solid preparation containing 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide is provided, namely, a solid preparation containing 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide and D-mannitol having a specific surface area of 1.0 m.sup.2/g or less.
Inventor(s):	Furuta; Shouji (Kyoto, JP), Mukai; Hironori (Kyoto, JP)
Assignee:	NIPPON SHINYAKU CO., LTD. (Kyoto, JP)
Application Number:	15/777,711
Patent Claims:	1. A solid, preparation comprising: 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide; and D-mannitol having a specific surface area of larger than 0.2 m.sup.2/g, and 1.0 m.sup.2/g or less; wherein the content of D-mannitol is: (a) such that the weight of D-mannitol is from 5 to 10000 parts by weight with respect to 1 part by weight of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide, (b) from 10 to 99 wt % of the total weight of the solid preparation, and (c) 20 wt % or more of the total weight of diluents contained in the solid preparation. 2. The solid preparation according to claim 1, further comprising a diluent other than D-mannitol and a binder. 3. The solid preparation according to claim 2, wherein the diluent other than D-mannitol is one type or two types selected from the group consisting of cornstarch, sucrose, and crystalline cellulose. 4. The solid preparation according to claim 2, wherein the binder is hydroxypropyl cellulose. 5. The solid preparation according to claim 1, further comprising: (d) one type or two types selected from the group consisting of cornstarch, sucrose, and crystalline cellulose; and (e) hydroxypropyl cellulose. 6. The solid preparation according to claim 5, wherein (f) the content of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide is from 0.1 to 2 wt % of the total weight of the solid preparation, (b) the content of D-mannitol is from 20 to 80 wt % of the total weight of the solid preparation, (g) the content of cornstarch is from 15 to 40 wt % of the total weight of the solid preparation, and (h) the content of hydroxypropyl cellulose is from 1 to 5 wt % of the total weight c f the solid preparation. 7. The solid preparation according to claim 1, wherein 2-{4-[N-5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsul- fonyl)acetamide is a Form-I crystal. 8. The solid preparation according to claim 1, wherein the solid preparation is a tablet or a granule. 9. A method for treating diabetic neuropathy, diabetic gangrene, a peripheral circulatory disturbance, chronic arterial occlusion, intermittent claudication, scleroderma, thrombosis, pulmonary hypertension, myocardial infarction, angina pectoris, glomerulonephritis, diabetic nephropathy, chronic renal failure, bronchial asthma, interstitial pneumonia, a chronic obstructive pulmonary disease, tubulointerstitial nephritis, an inflammatory bowel disease, or a symptom associated with spinal canal stenosis, the method comprising the step of administering to a subject, a solid preparation comprising: 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide; and D-mannitol having a specific surface area of larger than 0.2 m.sup.2/g, and 1.0 m.sup.2/g or less; wherein the content of D-mannitol is: (a) such that the weight of D-mannitol is from 5 to 10000 parts by weight with respect 1 part by weight of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide, (b) from 10 to 99 wt % of the total weight of the solid preparation, and (c) 20 wt % or more of the total weight of diluents contained in the solid preparation. 10. The method according to claim 9, wherein what is treated is pulmonary hypertension. 11. The method according to claim 9, wherein what is treated is a peripheral circulatory disturbance. 12. The method according to claim 9, wherein what is treated is chronic arterial occlusion. 13. The method according to claim 9, wherein what is treated is intermittent claudication. 14. The method according to claim 9, wherein what is treated is a symptom associated with spinal canal stenosis. 15. The method according to claim 9, wherein what is treated is interstitial pneumonia and the interstitial pneumonia treated is pulmonary fibrosis. 16. The method according to claim 9, wherein what is treated is scleroderma. 17. The method according to claim 9, wherein what is treated is chronic renal failure. 18. The method according to claim 9, wherein what is treated is tubulointerstitial nephritis. 19. The method according to claim 10, wherein the pulmonary hypertension treated is pulmonary arterial hypertension. 20. The method according to claim 19, wherein the solid preparation further comprises a diluent other than D-mannitol and a binder. 21. The method according to claim 19, wherein the solid preparation further comprises: (d) one type or two types selected from the group consisting of cornstarch, sucrose, and crystalline cellulose; and (e) hydroxypropyl cellulose. 22. The method according to claim 21, wherein the solid preparation comprises cornstarch, and (f) the content of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide is from 0.1 to 2 wt % of the total weight of the solid preparation, (b) the content of D-mannitol is from 20 to 80 wt % of the total weight of the solid preparation, (g) the content of cornstarch is from 15 to 40 wt % of the total weight of the solid preparation, and (h) the content of hydroxypropyl cellulose is from 1 to 5 wt % of the total weight of the solid preparation. 23. The method according to claim 19, wherein the solid preparation is a tablet. 24. The method according to claim 23, wherein D-mannitol has a specific surface area of larger than 0.2 m.sup.2/g and smaller than 0.7 m.sup.2/g, and the content of D-mannitol is: (a) such that the weight of D-mannitol is from 10 to 9500 parts by weight with respect to 1 part by weight of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide, (b) from 20 to 80 wt % of the total weight of the solid preparation, and (c) 50 wt % or more of the total weight of diluents contained in the solid preparation. 25. The method according to claim 24, wherein the solid preparation further comprises: (d) one type or two types selected from the group consisting of cornstarch, sucrose, and crystalline cellulose; and (e) hydroxypropyl cellulose. 26. The method according to claim 25, wherein the solid preparation comprises cornstarch, and (f) the content of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsu- lfonyl)acetamide is from 0.1 to 2 wt % of the total weight of the solid preparation, (g) the content of cornstarch is from 1.5 to 40 wt % of the total weight of the solid preparation, and (h) the content of hydroxypropyl cellulose is from 1 to 5 wt % of the total weight of the solid preparation.