Compositions and methods for the treatment of anorectal disorders

Abstract

Compositions and methods for the treatment of anorectal disorders are provided in which certain combinations of NO donors, PDE inhibitors, superoxide (O 2 − ) scavengers, β-adrenergic agonists, cAMP-dependent protein kinase activators, α 1 -adrenergic antagonists, L-type Ca 2+ channel blockers, estrogens, ATP-sensitive K + channel activators and smooth muscle relaxants are used.

1 . A method of treating an anorectal disorder, and for controlling the pain associated therewith, the method comprising administering to a subject in need of such treatment a therapeutically effective amount of a composition that comprises at least one internal anal sphincter relaxing agent selected from the group consisting of NO donors, phosphodiesterase type II inhibitors, phosphodiesterase type IV inhibitors, phosphodiesterase type V inhibitors, nonspecific phosphodiesterase inhibitors, superoxide scavengers, β-adrenergic agonists, cAMP-dependent protein kinase activators, α 1 -adrenergic antagonists, estrogens, L-type Ca 2+  channel blockers, ATP-sensitive K +  channel activators, adenosine receptor antagonists and smooth muscle relaxants.  
   
   
       2 . A method in accordance with  claim 1 , wherein said administering is by local application.  
   
   
       3 . A method according to  claim 1 , wherein said composition comprises a first relaxing agent that is a NO donor selected from the group consisting of nitroglycerin, L-arginine, SNAP, GSNO and SIN-1 and a second agent is selected from the group consisting of β 2 -adrenergic agonists and adrenergic receptor antagonists.  
   
   
       4 . A method in accordance with  claim 1 , wherein said composition comprises a first relaxing agent which is a NO donor selected from the group consisting of nitroglycerin, L-arginine, SNAP, GSNO and SIN-1 and a second agent which is an ATP sensitive K +  channel activator, an adenosine receptor antagonist, or a β 2 -adrenergic agonist.  
   
   
       5 . A method according to  claim 1 , wherein said composition comprises an adenosine receptor antagonist, an ATP sensitive K +  channel opener, or a β 2 -adrenergic agonist.  
   
   
       6 . A method in accordance with  claim 1 , wherein said anorectal disorder is an anal fissure.  
   
   
       7 . A method of  claim 1 , wherein said composition comprises a terbutaline, salbutamol, theophylline, dyphylline, minoxidil or diazoxide.  
   
   
       8 . A method of treating an anorectal disorder in a human, and for controlling the pain associated therewith, said method consisting essentially of administering a first agent which consists essentially of a selective PDE V inhibitor to said human.  
   
   
       9 . A method according to  claim 8 , wherein said method consists essentially of administering sildenafil as said PDE V inhibitor.  
   
   
       10 . A method according to  claim 8 , wherein said inhibitor is zaprinist, DMPPO, or MY-5445.  
   
   
       11 . A method according to  claim 8 , wherein said administering is via the oral route.  
   
   
       12 . A method according to  claim 11 , wherein said inhibitor is in the form of a lozenge, tablet or capsule.  
   
   
       13 . A method according to  claim 8 , wherein said disorder is selected from the group consisting of anal fissure, anal ulcer, hemorrhoidal diseases, levator spasm, disorders associated with hemorrhoidal pain, spasm of the internal anal sphincter, and post-operative rectal pain.  
   
   
       14 . A method according to  claim 13 , wherein said disorder is anal fissure.  
   
   
       15 . A method according to  claim 13 , wherein said disorder is a hemorrhoidal disease.  
   
   
       16 . A method according to  claim 13 , wherein said disorder is post-operative rectal pain.  
   
   
       17 . A method according to  claim 13 , wherein the disorder is exacerbated by hypertonicity or spasms of the anal sphincter muscle.  
   
   
       18 . A method according to  claim 9 , wherein said administering is via the oral route.  
   
   
       19 . A method according to  claim 9 , wherein said sildenafil is administered as a lozenge, tablet or capsule.  
   
   
       20 . A method according to  claim 9 , wherein said disorder is anal fissure.  
   
   
       21 . A method according to  claim 8 , wherein said administering is via the rectal route.