JPWO2020249979A5 - - Google Patents

Claims (38)

A pharmaceutical composition for use in a method of treating bradykinin-mediated non-hereditary angioedema (BK-AEnH) on demand, said composition comprising a compound of formula A or a pharmaceutically acceptable salt thereof and/or a solvate, the method comprising orally administering the composition on demand to a patient in need of treatment for bradykinin-mediated non-hereditary angioedema (BK-AEnH) things .

For use in the on-demand treatment of acute attacks of bradykinin -mediated non-hereditary angioedema (BK-AEnH), administered orally on demand upon recognition of symptoms of an acute BK-AEnH attack. The pharmaceutical composition of claim 1, wherein Recognized symptoms of acute BK-AEnH attacks include tissue swelling, malaise, headache, muscle pain, skin tingling, abdominal pain, nausea, vomiting, diarrhea, difficulty swallowing, hoarseness, shortness of breath, and/or mood swings. 3. The pharmaceutical composition of claim 2 , which is at least one of 4. The pharmaceutical composition according to claim 2 or 3 , administered orally on demand within 1 hour after symptoms of an acute BK-AEnH attack are recognized. Orally administered on demand within 30 minutes, 20 minutes, 10 minutes, or 5 minutes after symptoms of an acute BK-AEnH attack are recognized. pharmaceutical composition . The pharmaceutical composition according to any one of claims 2 to 5 , which is orally administered on demand in the prodromal phase of acute BK-AEnH attacks. 7. The pharmaceutical composition of Claim 6 , wherein the perceived symptom is at least one of mild swelling, abdominal pain, or skin redness. 8. The pharmaceutical composition of claim 7 , wherein said recognized condition is erythema marginata. The pharmaceutical composition of any one of claims 1-8 , wherein said treatment shortens the duration of said acute BK-AEnH attacks. 7. The pharmaceutical composition of claim 6 , wherein said treatment prevents said acute BK-AEnH attack from progressing to the swelling phase of acute BK-AEnH attack. 2. The pharmaceutical composition of claim 1, administered orally on demand to prophylactically reduce the likelihood of acute BK-AEnH attacks. 12. The pharmaceutical composition of claim 11 , administered orally on demand when an acute BK-AEnH attack is expected to be induced. 13. The pharmaceutical composition according to claim 11 or 12 , administered orally on demand to prevent acute BK-AEnH attacks. 14. The pharmaceutical composition according to claim 12 or 13, administered orally on demand when acute BK-AEnH attacks are expected to be induced by physical trauma and/or stress. 15. A pharmaceutical composition according to claim 14 , wherein the acute BK-AEnH attack is expected to be provoked by the physical trauma of dental procedures and/or the psychological stress associated with dental procedures. A pharmaceutical composition according to any one of claims 1 to 15 , further comprising a pharmaceutically acceptable excipient and administered as an oral dosage form. 17. The pharmaceutical composition according to claim 16 , wherein said oral dosage form is a tablet comprising microcrystalline cellulose as a diluent, croscarmellose sodium as a disintegrant and polyvinylpyrrolidone as a binder. 17. The oral dosage form of claim 16, wherein the oral dosage form is a tablet comprising microcrystalline cellulose as a diluent, croscarmellose sodium as a disintegrant, polyvinylpyrrolidone as a binder, and magnesium stearate as a lubricant. pharmaceutical composition. ( i) inhibit plasma kallikrein; (ii) reduce the cleavage of plasma prekallikrein; and/or (iii) reduce the production of factor XIIa from factor XII . Pharmaceutical composition as described. The compound of Formula A or the compound of Formula A, or 20. The pharmaceutical composition according to claim 19 , administered in doses of pharmaceutically acceptable salts and/or solvates thereof. 21. The pharmaceutical composition of claim 20 , wherein said patient is administered said composition comprising at least 60 mg of a compound of Formula A or a pharmaceutically acceptable salt and/or solvate thereof. A pharmaceutical composition according to any one of claims 1 to 21 , which blocks activation of the contact system for up to 6 hours. A medicament according to any one of claims 1 to 22 , wherein said compound of formula A or a pharmaceutically acceptable salt and/or solvate thereof is administered in a daily dose of 5 mg to 2000 mg. composition . The compounds of the formula A are 100 mg to 1500 mg, 300 mg to 1800 mg, 100 mg to 1400 mg , 200 mg to 1200 mg, 300 mg to 1200 mg, 600 mg to 1200 mg, 450 mg -900 mg, 500 mg, 450 MG ~ 600mg, 500mg -700mg, 800 mg ~ 24. The pharmaceutical composition of any one of claims 1-23 , administered in a daily dose of 1000 mg, 900 mg to 1400 mg, or 900 mg to 1200 mg. 25. The medicament according to any one of claims 1 to 24 , wherein the patient is administered a daily dose in two doses within 24 hours starting from the time the first dose is taken. composition . 26. The pharmaceutical composition according to claim 25 , wherein said two doses are administered separately or sequentially. 27. The pharmaceutical composition according to claim 25 or 26 , wherein said second dose is administered 2-6 hours from said first dose. 27. The pharmaceutical composition of claim 25 or 26, wherein said second dose is administered about 3-6 hours from said first dose. 27. The pharmaceutical composition of claim 25 or 26 , wherein said second dose is administered at least about 6 hours after said first dose. The pharmaceutical composition according to any one of claims 1 to 24 , which is administered to said patient as a dose three times a day . 31. The pharmaceutical composition of claim 30 , wherein said three doses are administered separately or sequentially. 32. The pharmaceutical composition of claim 30 or 31 , wherein said second and third doses are administered at least about 6 hours after the preceding dose. The pharmaceutical composition according to any one of claims 22-32 , wherein each dose comprises about 600 mg of said compound of formula A. 34. The pharmaceutical composition of Claim 33 , wherein each dose is administered as two tablets each containing about 300 mg of said compound of Formula A. 35. The pharmaceutical composition of any one of claims 1-34 , wherein said bradykinin-mediated non-hereditary angioedema (BK-AEnH) is not caused by an inherited genetic dysfunction, defect or mutation. things . The BK-AEnH is associated with non-hereditary angioedema, acquired angioedema, anaphylaxis-associated angioedema, angiotensin-converting enzyme (ACE ) inhibitor-induced angioedema , dipeptidyl peptidase-4 inhibitor-induced angioedema, and tPA-induced angioedema (tissue plasminogen activator-induced angioedema). Pharmaceutical composition as described. 36. The pharmaceutical composition according to claim 35 , wherein said AE-nC1 Inh is environmentally induced by air pollution and/or silver nanoparticles. said BK-AEnH is tPA-induced angioedema;
said patient has also been administered tissue plasminogen activator;
A pharmaceutical composition according to any one of claims 11 to 13 , wherein said composition is administered before, during or after administration of tissue plasminogen activator to said patient.