Compositions and methods for use against acne-induced inflammation and dermal matrix-degrading enzymes

Abstract

Acne-affected skin has been found to be accompanied by the presence of matrix-degrading enzymes such as MMPs and neutrophil elastase, induction of neutrophils, and a reduction in procollagen biosynthesis. This invention treats scarring and inflammation accompanying acne by administering, topically or systemically, at least one of (i) an inhibitor of the matrix degrading enzymes and (ii) a cytokine inhibitor that alleviates inflammation and thus also alleviate neutrophil infiltration. Alleviating the matrix degradation and renormalizing procollagen biosynthesis allows for reduced inflammation and better natural repair of acne-affected skin. Inhibiting cytokines alleviates induction of MMPs in resident skin cells, and also alleviates inflammation with its concommitant induction of neutrophils from the blood stream bringing MMPs and elastase into the acne lesion. Diminishing the presence of matrix-degrading enzymes in the acne lesion reduces imperfect repair of the skin and thus decreases scarring in acne-affected skin.

1 . A composition for alleviating acne scarring, comprising a compatible combination of: a non-retinoid inhibitor of at least one of MMP-1 and MMP-8 selected from at least one of AP-1 inhibitors and elastase inhibitors; and an active ingredient selected from the group consisting of comedolytics, antibacterials, anti-inflammatories, retinoids, glucocorticoids, and compatible mixtures thereof.  
     
     
         2 . The composition of  claim 1 , wherein the composition is applied topically and is provided in combination with a dermatologically-acceptable carrier.  
     
     
         3 . The composition of  claim 1 , wherein the composition is administered systemically.  
     
     
         4 . The composition of  claim 1 , wherein the active ingredient is a retinoid.  
     
     
         5 . The composition of  claim 1 , wherein the active ingredient is an antibacterial.  
     
     
         6 . The composition of  claim 5 , wherein the active ingredient is benzoyl peroxide.  
     
     
         7 . The composition of  claim 1 , wherein the inhibitor comprises a combination of an inhibitor of at least one of MMP-1 and MMP-8, and a neutrophil elastase inhibitor.  
     
     
         8 . A method for treating acne-affected skin, comprising the steps of: orally administering an active ingredient for the treatment of acne and topically administering a non-retinoid, non-glucocorticoid inhibitor of at least one of MMP-1 and MMP-8 to acne-affected skin.  
     
     
         9 . The method of  claim 8 , wherein the active ingredient is a retinoid or a tetracycline or a tetracycline derivative.  
     
     
         10 . The method of  claim 8 , wherein the inhibitor is selected from the group consisting of AP-1 inhibitors, elastase inhibitors, selectin inhibitors, and compatible mixtures thereof.  
     
     
         11 . The method of  claim 10 , comprising topically administering one or more inhibitors of MMP-1 and MMP-8.  
     
     
         12 . The method of  claim 8 , wherein the inhibitor is applied regularly from once every two days to twice daily.  
     
     
         13 . The method of  claim 12 , wherein the inhibitor is applied daily.  
     
     
         14 . The method of  claim 11 , further comprising topically administering an elastase inhibitor.  
     
     
         15 . The method of  claim 8 , wherein the inhibitor is a direct MMP inhibitor.  
     
     
         16 . The method of  claim 8 , wherein the inhibitor is an indirect MMP inhibitor.