Methods and compositions for treating and preventing mucositis

Abstract

A method of reducing or inhibiting mucositis in a patient, which includes administering an inflammatory cytokine inhibitor or a mast cell inhibitor, or a combination thereof, is disclosed

What is claimed is:  
     
         1 . A method of treating, inhibiting, or preventing mucositis in a human patient, said method comprising administering to said patient first and second different therapeutic agents, wherein said first therapeutic agent is an NSAID, an inflammatory cytokine inhibitor, or a mast cell inhibitor; and said second therapeutic agent is an inflammatory cytokine inhibitor, a mast cell inhibitor, an MMP inhibitor, an NSAID, or an NO inhibitor.  
     
     
         2 . The method of    claim 1   , wherein at least one of said first and second agents is an NSAID which is a COX-1 or COX-2 inhibitor.  
     
     
         3 . The method of    claim 2   , wherein said COX-1 inhibitor is indomethacin or flurbiprofin.  
     
     
         4 . The method of    claim 1   , wherein the first agent is an inflammatory cytokine inhibitor selected from an IL-6 inhibitor, a TNF-alpha inhibitor, an IL-1 inhibitor, and an interferon-gamma inhibitor.  
     
     
         5 . The method of    claim 4    wherein the first agent is a TNF-alpha inhibitor and the second agent is an MMP inhibitor.  
     
     
         6 . The method of    claim 1    wherein said MMP inhibitor is a tetracycline.  
     
     
         7 . The method of    claim 6    wherein said tetracycline is minocycline.  
     
     
         8 . The method of    claim 6    wherein the first agent is an NSAID.  
     
     
         9 . The method of    claim 1    wherein the NO inhibitor is aminoguanidine or guanidine.  
     
     
         10 . The method of    claim 1    wherein the TNF-alpha inhibitor is thalidomide.  
     
     
         11 . The method of    claim 1    wherein the first agent is a mast cell inhibitor selected from an antihistamine, a serine protease inhibitor, and a degranulation inhibitor.  
     
     
         12 . The method of    claim 1    wherein the first and second agents are provided mixed together in a composition.  
     
     
         13 . The method of    claim 12   , wherein the composition is a liquid adapted for use as an oral rinse.  
     
     
         14 . The method of    claim 12   , wherein the composition is a solid adapted for oral ingestion.  
     
     
         15 . A method of treating, inhibiting, or preventing mucositis in a human patient, said method comprising administering to said patient an effective amount of a therapeutic agent selected from an MMP inhibitor, an inflammatory cytokine inhibitor and a mast cell inhibitor.  
     
     
         16 . The method of    claim 15   , wherein the mast cell inhibitor is a degranulation inhibitor.  
     
     
         17 . The method of    claim 15   , wherein the mast cell inhibitor is an antihisitmine.  
     
     
         18 . The method of    claim 15   , wherein the mast cell inhibitor is a serine protease inhibitor.  
     
     
         19 . The method of    claim 15   , wherein the MMP inhibitor is a tetracycline.  
     
     
         20 . The method of    claim 19   , wherein the tetracycline is minocycline.  
     
     
         21 . The method of    claim 1   , wherein said method further comprises administering to said patient a third therapeutic agent in an amount sufficient to inhibit infection, wherein said third therapeutic agent is an antimicrobial compound.  
     
     
         22 . The method of    claim 1   , wherein said mucositis is induced by antineoplastic therapy.  
     
     
         23 . The method of    claim 22   , wherein said mucositis is induced by chemotherapy.  
     
     
         24 . The method of    claim 22   , wherein said mucositis is induced by radiation therapy.  
     
     
         25 . The method of    claim 22   , wherein said patient is a cancer patient preparing to undergo chemotherapy or radiation therapy.  
     
     
         26 . The method of    claim 22   , wherein said patient is a cancer patient currently undergoing chemotherapy or radiation therapy.  
     
     
         27 . The method of    claim 1   , wherein said mucositis is oral mucositis.  
     
     
         28 . A pharmaceutical composition for treating oral mucositis comprising 
 (a) a first therapeutic agent comprising an NSAID, an inflammatory cytokine inhibitor, or a mast cell inhibitor;    (b) a second, different therapeutic agent comprising an inflammatory cytokine inhibitor, a mast cell inhibitor, an MMP inhibitor, an NSAID, or an NO inhibitor; and    (c) a pharmaceutically acceptable carrier, wherein said first and second therapeutic agents are present in amounts sufficient to inhibit mucositis in a patient suffering from mucositis or at risk for mucositis.    
     
     
         29 . The pharmaceutical composition of    claim 28   , wherein said composition is formulated into a lozenge, a tablet, an oral rinse, an oral paste, or an oral gel.  
     
     
         30 . The pharmaceutical composition of    claim 28   , wherein said mast cell inhibitor is an antihistimine.  
     
     
         31 . The pharmaceutical composition of    claim 28   , wherein said anti-inflammatory agent is an NSAID.  
     
     
         32 . The pharmaceutical composition of    claim 31   , wherein said composition further comprises an anti-ulcer agent in an amount sufficient to inhibit gastric mucosal injury.  
     
     
         33 . The pharmaceutical composition of    claim 28   , wherein said anti-inflammatory agent is a cyclooxygenase-2 inhibitor.  
     
     
         34 . The pharmaceutical composition of    claim 28   , wherein said composition further comprises an antimicrobial agent in an amount sufficient to inhibit infection.