Pharmaceutical combinations

Abstract

Pharmaceutical combinations suitable for treating the lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in men are described herein. The combinations contain an alpha-adrenoceptor antagonist and a muscarinic antagonist that may be administered simultaneously, separately or sequentially. The methods of treatment using the combinations are particularly suitable for treating moderate or severe LUTS.

I claim:  
     
         1 . A product comprising a first pharmaceutically acceptable composition comprising an alpha-adrenoceptor antagonist and a second pharmaceutically acceptable composition comprising a muscarinic antagonist, wherein said product is a combined preparation for simultaneous, separate or sequential use of said first composition and said second composition.  
     
     
         2 . The product of    claim 1    wherein said alpha-adrenoceptor antagonist in said first composition is non-selective.  
     
     
         3 . The product of    claim 1    wherein said alpha-adrenoceptor antagonist in said first composition is selective for α 1  receptors.  
     
     
         4 . The product of    claim 3    wherein said alpha-adrenoceptor antagonist in said first composition is selected from the group consisting of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, doxazosin, tetrazosin, abanoquil, prazosin, and indoramin or pharmaceutically acceptable salts thereof.  
     
     
         5 . The product of    claim 1    wherein said muscarinic antagonist in said second composition is non-selective.  
     
     
         6 . The product of    claim 1    wherein said muscarinic antagonist in said second composition is selective for M 3  receptors.  
     
     
         7 . The product of    claim 1    wherein said muscarinic antagonist in said second composition is selected from the group consisting of darifenacin, tolterodine and oxybutynin or pharmaceutically acceptable salts thereof.  
     
     
         8 . The product of    claim 1    wherein said muscarinic antagonist is darifenacin or a pharmaceutically acceptable salt thereof.  
     
     
         9 . The product of    claim 1    wherein said first composition comprises doxazosin and said second composition comprises darifenacin or a pharmaceutically acceptable salt of either thereof.  
     
     
         10 . The product of    claim 1    wherein said first composition comprises 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline and said second composition comprises darifenacin or a pharmaceutically acceptable salt of either thereof.  
     
     
         11 . A medicament comprising an alpha-adrenoceptor antagonist in combination with a muscarinic antagonist.  
     
     
         12 . The medicament of    claim 11    wherein said alpha-adrenoceptor antagonist is non-selective.  
     
     
         13 . The medicament of    claim 11    wherein said alpha-adrenoceptor antagonist is selective for α 1  receptors.  
     
     
         14 . The medicament of    claim 11    wherein said alpha-adrenoceptor antagonist is selected from the group consisting of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, doxazosin, tetrazosin, abanoquil, prazosin, and indoramin or pharmaceutically acceptable salts thereof.  
     
     
         15 . The medicament of    claim 11    wherein said muscarinic antagonist is non-selective.  
     
     
         16 . The medicament of    claim 11    wherein said muscarinic antagonist is selective for M 3  receptors.  
     
     
         17 . The medicament of    claim 11    wherein said muscarinic antagonist is selected from the group consisting of darifenacin, tolterodine and oxybutynin or pharmaceutically acceptable salts thereof.  
     
     
         18 . The medicament of    claim 11    wherein said muscarinic antagonist is darifenacin, or a pharmaceutically acceptable salt thereof.  
     
     
         19 . The medicament of    claim 11    wherein said alpha-adrenoceptor antagonist is doxazosin and said muscarinic antagonist is darifenacin, or pharmaceutically acceptable salts of either thereof.  
     
     
         20 . The medicament of    claim 11    wherein said alpha-adrenoceptor antagonist is 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline and said muscarinic antagonist is darifenacin, or pharmaceutically acceptable salts of either thereof.  
     
     
         21 . A pharmaceutical composition comprising an alpha-adrenoceptor antagonist, a muscarinic antagonist and a pharmaceutically acceptable carrier.  
     
     
         22 . The composition of    claim 21    wherein said alpha-adrenoceptor antagonist is non-selective or selective for α 1  receptors.  
     
     
         23 . The composition of    claim 21    wherein said alpha-adrenoceptor antagonist is selected from the group consisting of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, doxazosin, tetrazosin, abanoquil, prazosin, and indoramin or pharmaceutically acceptable salts thereof.  
     
     
         24 . The composition of    claim 21    wherein said muscarinic antagonist is non-selective or selective for M 3  receptors.  
     
     
         25 . The composition of    claim 21    wherein said muscarinic antagonist is selected from the group consisting of darifenacin, tolterodine and oxybutynin or pharmaceutically acceptable salts thereof.  
     
     
         26 . The composition of    claim 21    wherein said muscarinic antagonist is darifenacin, or a pharmaceutically acceptable salt thereof.  
     
     
         27 . The composition of    claim 21    wherein said alpha-adrenoceptor antagonist is doxazosin and said muscarinic antagonist is darifenacin, or pharmaceutically acceptable salts of either thereof.  
     
     
         28 . The composition of    claim 21    wherein said alpha-adrenoceptor antagonist is 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline and said muscarinic antagonist is darifenacin, or pharmaceutically acceptable salts of either thereof.  
     
     
         29 . A method for treating the lower urinary tract symptoms associated with benign hyperplasia in mammals comprising administering to a mammal in need thereof an effective amount of an alpha-adrenoceptor antagonist in combination with a muscarinic antagonist.  
     
     
         30 . The method of    claim 29    wherein said alpha-adrenoceptor antagonist and said muscarinic antagonist is administered simultaneously.  
     
     
         31 . The method of    claim 29    wherein said alpha-adrenoceptor antagonist and said muscarinic antagonist is administered separately.  
     
     
         32 . The method of    claim 29    wherein said alpha-adrenoceptor antagonist and said muscarinic antagonist is administered sequentially.  
     
     
         33 . The method of    claim 29    wherein the alpha-adrenoceptor antagonist is non-selective or selective for α 1  receptors.  
     
     
         34 . The method of    claim 29    wherein said alpha-adrenoceptor antagonist is selected from the group consisting of 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline, doxazosin, tetrazosin, abanoquil, prazosin, and indoramin or pharmaceutically acceptable salts thereof.  
     
     
         35 . The method of    claim 29    wherein said muscarinic antagonist is non-selective or selective for M 3  receptors.  
     
     
         36 . The method of    claim 29    wherein said muscarinic antagonist is selected from the group consisting of darifenacin, tolterodine and oxybutynin or pharmaceutically acceptable salts thereof.  
     
     
         37 . The method of    claim 29    wherein said muscarinic antagonist is darifenacin, or a pharmaceutically acceptable salt thereof.  
     
     
         38 . The method of    claim 29    wherein said alpha-adrenoceptor antagonist is doxazosin and said muscarinic antagonist is darifenacin, or pharmaceutically acceptable salts of either thereof.  
     
     
         39 . The method of    claim 29    wherein said alpha-adrenoceptor antagonist is 4-amino-6,7-dimethoxy-2-(5-methanesulfonamido-1,2,3,4-tetrahydroisoquinol-2-yl)-5-(2-pyridyl)quinazoline and said muscarinic antagonist is darifenacin, or pharmaceutically acceptable salts of either thereof.