Methods and compositions using norastemizole in combination with leukotriene inhibitors

Abstract

Methods and pharmaceutical compositions employing norastemizole and a leukotriene inhibitor for the treatment or prevention of inflammation or allergic disorders, such as asthma or the symptoms thereof. Also included are methods and compositions employing norastemizole and a decongestant for the treatment or prevention of inflammation or allergic disorders, such as asthma or the symptoms thereof.

What is claimed is:  
     
         1 . A method of treating or preventing asthma or the symptoms thereof in a human which comprises administering to a human a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a leukotriene inhibitor, or a pharmaceutically acceptable salt thereof.  
     
     
         2 . A method of treating or preventing asthma or the symptoms thereof in a human which comprises administering to a human a composition, said composition comprising (i) a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof; (ii) a therapeutically effective amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, selected from the group consisting of 5-lipoxygenase inhibitors, 5-lipoxygenase activating protein antagonists, leukotriene receptor antagonists, and mixtures thereof; and a pharmaceutically acceptable carrier or excipient.  
     
     
         3 . The method of  claim 1 , wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         4 . The method of  claim 2 , wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         5 . The method of  claim 1 ,  2 ,  3 , or  4  wherein the administering further comprises a therapeutically effective amount of a decongestant, or a pharmaceutically acceptable salt thereof.  
     
     
         6 . The method of  claim 1  wherein said human has asthma.  
     
     
         7 . A method of treating or preventing dermatitis in a human which comprises administering to a human a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a leukotriene inhibitor, or a pharmaceutically acceptable salt thereof.  
     
     
         8 . A method of treating or preventing dermatitis in a human which comprises administering to a human a composition, said composition comprising (i) a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof; (ii) a therapeutically effective amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, selected from the group consisting of 5-lipoxygenase inhibitors, 5-lipoxygenase activating protein antagonists, leukotriene receptor antagonists, and mixtures thereof; and a pharmaceutically acceptable carrier or excipient.  
     
     
         9 . The method of  claim 7  wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         10 . The method of  claim 8  wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         11 . The method of  claim 7 ,  8 ,  9 , or  10  wherein the administering further comprises a therapeutically effective amount of a decongestant, or a pharmaceutically acceptable salt thereof.  
     
     
         12 . A method of treating or preventing allergic rhinitis in a human which comprises administering to a human a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a leukotriene inhibitor, or a pharmaceutically acceptable salt thereof.  
     
     
         13 . A method of treating or preventing allergic rhinitis in a human which comprises administering to a human a composition, said composition comprising (i) a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof; (ii) a therapeutically effective amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, selected from the group consisting of 5-lipoxygenase inhibitors, 5-lipoxygenase activating protein antagonists, leukotriene receptor antagonists, and mixtures thereof; and a pharmaceutically acceptable carrier or excipient.  
     
     
         14 . The method of  claim 12  wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         15 . The method of  claim 13 , wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         16 . The method of  claim 12 ,  13 ,  14 , or  15  wherein the administering further comprises a therapeutically effective amount of a decongestant, or a pharmaceutically acceptable salt thereof.  
     
     
         17 . A method of treating or preventing inflammation in a human which comprises administering to a human a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a leukotriene inhibitor, or a pharmaceutically acceptable salt thereof.  
     
     
         18 . A method of treating or preventing inflammation in a human which comprises administering to a human a composition, said composition comprising (i) a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof; (ii) a therapeutically effective amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, selected from the group consisting of 5-lipoxygenase inhibitors, 5-lipoxygenase activating protein antagonists, leukotriene receptor antagonists, and mixtures thereof; and a pharmaceutically acceptable carrier or excipient.  
     
     
         19 . The method of  claim 17  wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         20 . The method of  claim 18 , wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         21 . The method of  claim 17 ,  18 ,  19 , or  20  wherein the administering further comprises a therapeutically effective amount of a decongestant, or a pharmaceutically acceptable salt thereof.  
     
     
         22 . A method for treating or preventing a condition responsive to leukotriene inhibition which comprises administering a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a leukotriene inhibitor, or a pharmaceutically acceptable salt thereof.  
     
     
         23 . A method of treating or preventing a condition responsive to leukotriene inhibition which comprises administering to a human a composition, said composition comprising (i) a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof; (ii) a therapeutically effective amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, selected from the group consisting of 5-lipoxygenase inhibitors, 5-lipoxygenase activating protein antagonists, leukotriene receptor antagonists, and mixtures thereof; and (iii) a pharmaceutically acceptable carrier or excipient.  
     
     
         24 . The method of  claim 22  wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         25 . The method of  claim 23 , wherein the administration of the amount norastemizole, or a pharmaceutically acceptable salt thereof, and the amount of leukotriene inhibitor, or a pharmaceutically acceptable salt thereof, avoids the concomitant liability of adverse effects associated with the administration of non-sedating antihistamines.  
     
     
         26 . The method of  claim 22 ,  23 ,  24 , or  25  wherein the administering further comprises a therapeutically effective amount of a decongestant, or a pharmaceutically acceptable salt thereof.  
     
     
         27 . The method of  claim 22  wherein the condition responsive to leukotriene inhibition comprises asthma or a symptom thereof.  
     
     
         28 . The method of  claim 22  wherein the condition responsive to leukotriene inhibition comprises an allergic condition.  
     
     
         29 . The method of  claim 22  wherein the condition responsive to leukotriene inhibition comprises inflammation.  
     
     
         30 . The method of  claim 1 ,  2 ,  7 ,  8 ,  12 ,  13 ,  17 ,  18 ,  22 , or  23  wherein the amount of norastemizole administered is from about 1 mg to about 200 mg per day.  
     
     
         31 . The method of  claim 30  wherein the amount of norastemizole administered is from about  10  mg to about 100 mg per day.  
     
     
         32 . The method of  claim 1 ,  2 ,  7 ,  8 ,  12 ,  13 ,  17 ,  18 ,  22 , or  23  wherein the compositions are administered as a nasal or oral spray.  
     
     
         33 . The method of  claim 1 ,  2 ,  7 ,  8 ,  12 ,  13 ,  17 ,  18 ,  22 , or  23  wherein at least one of the norastemizole and the leukotriene inhibitor is administered as a nasal or oral spray.  
     
     
         34 . The method of  claim 1 ,  2 ,  7 ,  8 ,  12 ,  13 ,  17 ,  18 ,  22 , or  23  wherein at least one of the norastemizole and the leukotriene inhibitor is administered in an oral solid dosage form.  
     
     
         35 . The method of  claim 3 ,  9 ,  14 ,  19 , or  24  wherein the norastemizole is administered as a nasal or oral spray.  
     
     
         36 . The method of  claim 1 ,  2 ,  7 ,  8 ,  12 ,  13 ,  17 ,  18 ,  22 , or  23  wherein the leukotriene inhibitor is a 5-lipoxygenase inhibitor.  
     
     
         37 . The method of  claim 36 , wherein the 5-lipoxygenase inhibitor is selected from the group consisting of zileuton, docebenone, piripost, ICI-D2318, and mixtures thereof.  
     
     
         38 . The method of  claim 1 ,  2 ,  7 ,  8 ,  12 ,  13 ,  17 ,  18 ,  22 , or  23  wherein the leukotriene inhibitor is a 5-lipoxygenase activating protein.  
     
     
         39 . The method of  claim 38 , wherein the 5-lipoxygenase activating protein is selected from the group consisting of MK-591, MK-886, and mixtures thereof.  
     
     
         40 . The method of  claim 1 ,  2 ,  7 ,  8 ,  12 ,  13 ,  17 ,  18 ,  22 , or  23  wherein the leukotriene inhibitor is a leukotriene receptor antagonist.  
     
     
         41 . The method of  claim 40 , wherein the leukotriene receptor antagonist is selected from the group consisting of 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-(((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, and salts and mixtures thereof.  
     
     
         42 . A pharmaceutical composition which comprises a therapeutically effective amount of norastemizole, or a pharmaceutically acceptable salt thereof; a therapeutically effective amount of a leukotriene inhibitor, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier or excipient.  
     
     
         43 . The pharmaceutical composition of  claim 42  which further comprises a therapeutically effective amount of a decongestant, or a pharmaceutically acceptable salt thereof.  
     
     
         44 . A pharmaceutical composition which comprises from about 1 mg to about 200 mg of norastemizole, or a pharmaceutically acceptable salt thereof, and from about 20 mg to about 2,500 mg of 5-lipoxygenase inhibitor, or a pharmaceutically acceptable salt thereof.  
     
     
         45 . A pharmaceutical composition which comprises from about 1 mg to about 200 mg of norastemizole, or a pharmaceutically acceptable salt thereof, and from about 20 mg to about 2500 mg of 5-lipoxygenase activating protein antagonist, or a pharmaceutically acceptable salt thereof.  
     
     
         46 . A pharmaceutical composition which comprises from about 1 mg to about 200 mg of norastemizole, or a pharmaceutically acceptable salt thereof, and from about 2 mg to about 200 mg of leukotriene receptor antagonist, or a pharmaceutically acceptable salt thereof.  
     
     
         47 . The composition of  claim 42 ,  43 ,  44 ,  45 , or  46  administered as a nasal or oral spray.  
     
     
         48 . The composition of  claim 42 ,  43 ,  44 ,  45 , or  46  wherein at least one of the norastemizole and the leukotriene inhibitor is administered as a nasal or oral spray.  
     
     
         49 . The composition of  claim 42 ,  43 ,  44 ,  45 , or  46  wherein at least one of the norastemizole and the leukotriene inhibitor is administered in an oral solid dosage form.