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 α 2  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 - 28 . (canceled) 
   
   
       29 . A method of treating edema and the symptoms associated therewith, comprising topically administering to the skin of a patient in need of such treatment a composition comprising:
 a therapeutically effective amount of at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof; and   a pharmaceutically acceptable carrier.   
   
   
       30 . The method according to  claim 29 , 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. 
     
   
   
       31 . The method according to  claim 30 , wherein the compounds are selected from the group consisting of brimonidine, naphazoline, tetrahydrozaline, oxymetazoline, xylometazoline, epinephrine, nerepinephrine, phenylephrine, and methoxamine. 
   
   
       32 . The method according to  claim 30 , wherein the compound is brimonidine, or its analogs, or pharmaceutically acceptable salts thereof. 
   
   
       33 . The method according to  claim 32 , wherein the compound is brimonidine tartrate. 
   
   
       34 . The method according to  claim 29 , 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. 
   
   
       35 . The method according to  claim 29 , 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. 
   
   
       36 . The method according to  claim 29 , wherein the composition acts locally in the skin of the patient. 
   
   
       37 . The method according to  claim 29 , wherein the edema is cutaneous edema.