Pharmaceutical Compositions
Disclosed are inhalable medicaments and methods based on an anticholinergic in combination with a corticosteroid, and a long acting beta agonist, for simultaneous or sequential administration in the prevention or treatment of a respiratory, inflammatory or obstructive airway disease. In addition, disclosed are inhalable medicaments and methods based on combinations of an anticholinergic and a corticosteroid; an anticholinergic and a long acting beta agonist; or a corticosteroid and a long acting beta agonist, for simultaneous or sequential administration in the prevention or treatment of a respiratory, inflammatory or obstructive airway disease. Also disclosed are inhalable medicaments and methods comprising a phosphodiesterase IV inhibitor for administration in the prevention or treatment of a respiratory, inflammatory or obstructive airway disease.
1 . A medicament comprising, separately or together, (A) an anticholinergic, (B) a corticosteroid, and (C) a long acting beta agonist, for simultaneous or sequential administration in the prevention or treatment of a respiratory, inflammatory or obstructive airway disease, each of (A), (B), and (C) being in an inhalable form.
2 . The medicament of claim 1 which is a pharmaceutical composition comprising an inhalable mixture of effective amounts of (A) and (B) and (C), optionally together with a pharmaceutically acceptable carrier.
3 . The medicament of claim 2 , which is an aerosol comprising a mixture of (A) and (B) and (C) in solution or dispersion in a propellant, or a combination of an aerosol containing (A) in solution or dispersion in a propellant with an aerosol containing (B) in solution or dispersion in a propellant with an aerosol containing (C) in solution or dispersion in a propellant.
4 - 5 . (canceled)
6 . The medicament of claim 3 , which is a nebulizable composition comprising a dispersion of (A) and (B) and (C) in an aqueous, organic or aqueous/organic medium or a combination of a dispersion of (A) in said medium with a dispersion of (B) in said medium with a dispersion of (C) in said medium.
7 . The medicament of claim 2 , which is a dry powder comprising finely divided (A) or (B) or (C), or finely divided (A) and (B) and (C), optionally together with a pharmaceutically acceptable carrier in finely divided form.
8 . The medicament of claim 7 , in which the carrier is present and is a saccharide.
9 - 10 . (canceled)
11 . (canceled)
12 . A medicament comprising, separately or together, (A) an anticholinergic, (B) a corticosteroid, and (C) a long acting beta agonist, for simultaneous or sequential administration in the prevention or treatment of a respiratory, inflammatory or obstructive airway disease, each of (A), (B), and (C) being in inhalable form, wherein the anticholinergic is glycopyrrolate or a pharmaceutically acceptable salt or hydrate thereof, wherein the corticosteroid is mometasone furoate or a pharmaceutically acceptable salt or hydrate thereof, and wherein the long acting beta agonist is carmoterol, indacaterol or a pharmaceutically acceptable salt or hydrate of any of the above, or a combination of two or more of the above.
13 . The medicament of claim 1 , wherein the anticholinergic is (R)-3-[2-hydroxy-2,2-(dithien-2-yl)acetoxy]-1-1 [2-(phenyl)ethyl]-1-azoniabicyclo[2.2.2]octane, glycopyrrolate, ipratropium bromide, oxitropium bromide, atropine methyl nitrate, atropine sulfate, ipratropium, belladonna extract, scopolamine, scopolamine methobromide, methscopolamine, homatropine methobromide, hyoscyamine, isopriopramide, orphenadrine, benzalkonium chloride, tiotropium bromide, GSK202405, or a pharmaceutically acceptable salt or hydrate of any of the above, or a combination of two or more of the above.
14 . (canceled)
15 . The medicament of claim 1 , wherein the anticholinergic is glycopyrrolate or a pharmaceutically acceptable salt or hydrate thereof.
16 . The medicament of claim 1 , wherein the corticosteroid is mometasone furoate; beclomethasone dipropionate; budesonide; fluticasone; dexamethasone; flunisolide; triamcinolone; (22R)-6.alpha.,9.alpha.-difluoro-11.beta.,21-dihydroxy-16.alpha.,17.alpha.-propylmethylenedioxy-4-pregnen-3,20-dione, tipredane, GSK685698, GSK799943 or a pharmaceutically acceptable salt or hydrate of any of the above, or a combination of two or more of the above.
17 . (canceled)
18 . The medicament of claim 15 , wherein the corticosteroid is mometasone furoate or a pharmaceutically acceptable salt or hydrate thereof.
19 . The medicament of claim 1 , wherein the long acting beta agonist is carmoterol, indacaterol, TA-2005, albuterol, terbutaline, salmeterol, bitolterol, formoterol, fenoterol, metaprotenerol, GSK159802, GSK642444, GSK159797, GSK597901, GSK678077, or a pharmaceutically acceptable salt or hydrate of any of the above, or a combination of two or more of the above.
20 . (canceled)
21 . The medicament of claim 1 , wherein the long acting beta agonist is indacaterol or a pharmaceutically acceptable salt or hydrate thereof.
22 . (canceled)
23 . The medicament of claim 21 , wherein the corticosteroid is mometasone furoate or a pharmaceutically acceptable salt or hydrate thereof.
24 - 28 . (canceled)
29 . The medicament of claim 25 , wherein the anticholinergic is glycopyrrolate or a pharmaceutically acceptable salt or hydrate thereof, wherein the corticosteroid is mometasone furoate or a pharmaceutically acceptable salt or hydrate thereof, wherein the long acting beta agonist is carmoterol, indacaterol or a pharmaceutically acceptable salt or hydrate of any of the above, or a combination of two or more of the above, and wherein the phosphodiesterase IV inhibitor is a xinafoate salt of 1-[[5-(1(S)-aminoethyl)-2-[8-methoxy-2-(trifluoromethyl)-5-quinolinyl]-4-oxazolyl]carbonyl]-4(R)-[(cyclopropylcarbonyl)amino]-L-proline, ethyl ester.
30 - 37 . (canceled)
38 . A method of treating respiratory diseases comprising administering a medicament comprising, (A) an anticholinergic, (B) a corticosteroid, and (C) a long acting beta agonist and optionally a phosphodiesterase IV inhibitor.
39 . The method of claim 38 , wherein administration of said medicament is once daily.
40 . The method of claim 38 , wherein said respiratory disease is a lower airway or upper airway disease.
41 . The method of claim 38 , wherein said respiratory disease is asthma or chronic obstructive disease.
42 . Method of manufacturing an aerosol comprising a medicament comprising, separately or together, (A) an anticholinergic, (B) a corticosteroid, and (C) a long acting beta agonist and optionally (D) a phosphodiesterase IV inhibitor comprising a process selected from the group consisting of a cold fill process or a pressure fill process.
43 . A pharmaceutical kit comprising at least one device, at least one pharmaceutical composition comprising, (A) an anticholinergic, (B) a corticosteroid, and (C) a long acting beta agonist in at therapeutically effective amount and instructions for administering (A) and (B) and (C).
44 . The kit according to claim 43 , wherein said device is selected from the group consisting of a metered dose inhaler, dry powder inhaler, a nebulizer and combinations of two or more thereof.
45 . The kit according to claim 43 , wherein said pharmaceutical composition further comprises a phosphodiesterase IV inhibitor.