(R,r)-Formoterol in Combination with Other Pharmacological Agents
This invention related to methods of treating, preventing and managing various pulmonary diseases or disorders using stereomerically pure (R,R)-formoterol in combination with other pharmacological agents such as leukotriene inhibitors and neurokinin receptor antagonists. Pharmaceutical compositions comprising (R,R)-formoterol and other pharmacological agents are also disclosed.
1 . A method of treating or managing a pulmonary disease or disorder which comprises administering to a patient a therapeutically effective amount of stereomerically pure (R,R) formoterol, or a pharmaceutically acceptable salt or solvate thereof, and a therapeutically effective amount of a leukotriene inhibitor, or a pharmaceutically acceptable salt or solvate thereof.
2 - 3 . (canceled)
4 . The method of claim 1 , wherein stereomerically pure (R,R) formoterol, or a pharmaceutically acceptable salt or solvate thereof, and the leukotriene inhibitor, or a pharmaceutically acceptable salt or solvate thereof, are concurrently administered.
5 . The method of claim 1 , wherein stereomerically pure (R,R) formoterol, or a pharmaceutically acceptable salt or solvate thereof, and the leukotriene inhibitor, or a pharmaceutically acceptable salt or solvate thereof, are sequentially administered.
6 . The method of claim 1 , wherein the leukotriene inhibitor is a 5-lipoxygenase inhibitor, 5-lipoxygenase activating protein antagonist, or a leukotriene receptor antagonist.
7 . The method of claim 6 , wherein the leukotriene inhibitor is a 5-lpoxygenase inhibitor.
8 . The method of claim 7 , wherein the 5-lipoxygenase inhibitor is zileuton, docebenone, piripost or ICI-D2318.
9 . The method of claim 6 , wherein the leukotriene inhibitor is a 5-lipoxygenase activating protein antagonist.
10 . The method of claim 9 , wherein the 5-lipoxygenase activating protein antagonist is MK-591 or MK-886.
11 . The method of claim 6 , wherein the leukotriene inhibitor is a leukotriene receptor antagonist.
12 . The method of claim 11 , wherein the leukotriene receptor antagonist is zafirlukast, montelukast, pranlukast, sodium 1-(((R)-(3-(2-(6,7-difluoro-2-quinolinyl)ethynyl)phenyl-3-(2-(2-hydroxy-2-propyl)phenyl)thio)methyl) cyclopropaneacetate, 1-(((R)-(3-(2-(2,3-dichlorothieno[3,2-b]pyridin-5-yl)-(E)-ethenyl)phenyl)-3-(2-(1-hydroxy- 1-methylethyl)phenyl)propyl)thio)methyl) cyclopropaneacetic acid, or (E)-8-[2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl]-2-(1H-tetrazol-5-yl)-4H- 1-benxopyran-4-one.
13 . A method of treating or managing a pulmonary disease or disorder which comprises administering to a patient a therapeutically effective amount of stereomerically pure (R,R) formoterol, or a pharmaceutically acceptable salt or solvate thereof, and a therapeutically effective amount of a neurokinin receptor antagonist, or a pharmaceutically acceptable salt or solvate thereof.
14 - 15 . (canceled)
16 . The method of claim 13 , wherein stereomerically pure (R,R) formoterol, or a pharmaceutically acceptable salt or solvate thereof, and the neurokinin receptor antagonist, or a pharmaceutically acceptable salt or solvate thereof, are concurrently administered.
17 . The method of claim 13 , wherein stereomerically pure (R,R) formoterol, or a pharmaceutically acceptable salt or solvate thereof, and the neurokinin receptor antagonist, or a pharmaceutically acceptable salt or solvate thereof, are sequentially administered.
18 . The method of 13 , wherein the neurokinin receptor antagonist is cyclo[3-amino-L-alanyl-L-leucyl-N-[2-(acetylamino)-2-deoxy-β-D-glucopyranosyl-L-asparaginyl-L-alpha-aspartyl-L-tryptophyl-L-phenylalanyl]-(4-1)-lactam, Cam-2445, FK224, L-754,030, L-733,060, R116301, SR48968, SR140333, SR142801, or ZD-6021.
19 . The method of claim 18 , wherein the neurokinin receptor antagonist is cyclo[3-amino-L-alanyl-L-leucyl-N-[2-(acetylamino)-2-deoxy-β-D-glucopyranosyl-L-asparaginyl-L-alpha-aspartyl-L-tryptophyl-L-phenylalanyl]-(4-1)-lactam.
20 . The method of claim 1 or 13, wherein the pulmonary disease or disorder is respiratory failure; adult respiratory distress syndrome; chronic obstructive airway disorders such as, but not limited to, asthma, chronic obstructive pulmonary disease and giant bullae; acute bronchitis; chronic bronchitis; emphysema; reversible obstructive airway disease; nocturnal asthma; exercise induced bronchospasm; bronchiectasis; atelectasis; pulmonary embolism; pneumonia; lung abscess; hypersensitivity of the lung; or Goodpasture's syndrome.
21 . The method of claim 1 or 13 , wherein the treatment is long-term maintenance treatment of asthma.
22 . (canceled)
23 . The method of claim 1 or 13 , wherein the management is long-term management of bronchoconstriction associated with chronic obstructive pulmonary disease.
24 . The method of claim 23 , wherein the chronic obstructive pulmonary disease is chronic bronchitis or emphysema.
25 . The method of claim 20 , wherein the hypersensitivity of the lung is hypersensitivity pneumonitis, eosinophilic pneumonias or allergic bronchopulmonary aspergillosis.
26 . The method of claim 20 , wherein the pulmonary disease or disorder is a chronic obstructive airway disorder.
27 . The method of claim 26 , wherein the chronic obstructive airway disorder is asthma or chronic obstructive pulmonary disease.
28 - 43 . (canceled)