Compounds, formulations, and methods for treating or preventing inflammatory skin disorders

Abstract

In methods, compounds, and topical formulations for treatment of inflammatory skin disorders incorporating compounds represented by the formulas below: wherein each of R 1 , R 2 , and R 3 is independently hydrogen, hologen, alkyl, or alkoxy; each of R 4 and R 5 is independently hydrogen, alkyl, or alkoxy; and each of R 6 and R 7 is independently hydrogen, nitro, alkyl, or alkoxy; wherein each of A 1 , A 3 , and A 4 is independently hydrogen or alkyl; and A 2 is independently hydrogen or hydroxy; and wherein each of B 1 , B 2 , and B 3 is independently hydrogen, hydroxy, or alkoxy; and each of B 4 and B 5 is independently hydrogen or alkyl, applying such compounds topically as sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions to treat inflammatory skin disorders and the symptoms associated therewith.

1 . A method of treating or preventing an inflammatory skin disorder and the symptoms associated therewith, comprising topically administering to the skin of a patient in need of such treatment or prevention a composition comprising: 
 a therapeutically effective amount of at least one of an a2 adrenergic receptor agonist and a pharmaceutically acceptable salt thereof; and    a pharmaceutically acceptable carrier;    wherein the inflammatory skin disorder is not rosacea.    
     
     
         2 . The method according to  claim 1  wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is selected from the group consisting of the compounds shown below:  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently hydrogen, hologen, alkyl, or alkoxy; each of R 4  and R 5  is independently hydrogen, alkyl, or alkoxy; and each of R 6  and R 7  is independently hydrogen, nitro, alkyl, or alkoxy;  
         wherein each of A 1 , A 3 , and A 4  is independently hydrogen or alkyl; and A 2  is independently hydrogen or hydroxy; and  
         wherein each of B 1 , B 2 , and B 3  is independently hydrogen, hydroxy, or alkoxy; and each of B 4  and B 5  is independently hydrogen or alkyl.  
       
     
     
         3 . The method according to  claim 2 , wherein the compounds are selected from the group consisting of brimonidine, naphazoline, tetrahydrozaline, oxymetazoline, xylometazoline, epinephrine, nerepinephrine, phenylephrine, and methoxamine.  
     
     
         4 . The method according to  claim 1 , wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is a reversible α 2  adrenergic receptor agonist or a pharmaceutically acceptable salt thereof.  
     
     
         5 . The method according to  claim 1 , wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is administered in an amount sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient.  
     
     
         6 . The method according to  claim 1 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         7 . The method according to  claim 1 , wherein the composition acts locally in the skin of the patient.  
     
     
         8 . A topical composition suitable for treating or preventing the symptoms of an inflammatory dermatologic disorder, comprising: 
 at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof;    and a pharmaceutically acceptable carrier;    wherein the inflammatory dermatologic disorder is not rosacea.    
     
     
         9 . The topical composition according to  claim 8 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of sprays, mists, aerosols, solutions, lotions, gels, creams, ointments, pastes, unguents, emulsions, and suspensions.  
     
     
         10 . The topical composition according to  claim 8 , wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is selected from the group consisting of the compounds shown below:  
       
         
           
           
               
               
           
         
         wherein each of R 1 , R 2 , and R 3  is independently hydrogen, hologen, alkyl, or alkoxy; each of R 4  and R 5  is independently hydrogen, alkyl, or alkoxy; and each of R 6  and R 7  is independently hydrogen, nitro, alkyl, or alkoxy;  
         wherein each of A 1 , A 3 , and A 4  is independently hydrogen or alkyl; and A 2  is independently hydrogen or hydroxy; and  
         wherein each of B 1 , B 2 , and B 3  is independently hydrogen, hydroxy, or alkoxy; and each of B 4  and B 5  is independently hydrogen or alkyl.  
       
     
     
         11 . The topical composition according to  claim 8 , wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is selected from the group consisting of brimonidine, naphazoline, tetrahydrozoline, oxymetazoline, xylometazoline, epinephrine, norepinephrine, phenylephrine, and methoxamine.  
     
     
         12 . The topical composition according to  claim 8 , wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         13 . The topical composition according to  claim 8 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         14 . The topical composition according to  claim 9 , wherein the pharmaceutically acceptable carrier is an aqueous gel comprising water, and a water-gelling amount of a pharmaceutically acceptable gelling agent selected from the group consisting of carbomers, glycerine polyacrylate, and mixtures thereof, the topical composition having a physiologically acceptable pH.  
     
     
         15 . The topical composition according to  claim 14 , wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         16 . The topical composition according to  claim 14 , wherein the pH value of the composition is in the range of about 5 to 8.  
     
     
         17 . The topical composition according to  claim 14 , further comprising a preservative.  
     
     
         18 . The topical composition according to  claim 14 , further comprising a local anesthetic.  
     
     
         19 . The topical composition according to  claim 14 , further comprising a skin humectant.  
     
     
         20 . A package for a topical composition suitable for treating or preventing the symptoms of rosacea comprising at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, comprising a container and instructions for use of the topical composition.  
     
     
         21 . The topical composition according to  claim 9 , wherein the pharmaceutically acceptable carrier is at least one of a cream and an ointment comprising stearic acid, stearyl alcohol, cetyl alcohol, glycerin, and water, the topical composition having a physiologically acceptable pH.  
     
     
         22 . The topical composition according to  claim 21 , wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is present in an amount in the range of about 0.01 to 5 weight percent.  
     
     
         23 . The topical composition according to  claim 21 , wherein the pH value of the composition in the range of about 5 to 8.  
     
     
         24 . The topical composition according to  claim 21 , further comprising a preservative.  
     
     
         25 . The topical composition according to  claim 21 , further comprising a local anesthetic.  
     
     
         26 . The topical composition according to  claim 21 , further comprising a skin humectant.  
     
     
         27 . The topical composition according to  claim 8 , wherein the at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof is provided in a concentration sufficient to decrease blood flow through the small arteries or arterioles of the skin of the patient to which it is applied.  
     
     
         28 . The topical composition according to  claim 8 , wherein the composition acts locally in the skin of the patient.