Methods and compositions for safe and effective treatment of erythema

Abstract

Improved methods and compositions for safe and effective treatment of erythema or a symptom associated with erythema in a subject are described. The methods involve topically applying to an affected skin area a topical composition comprising about 0.3% to about 10% by weight of brimonidine and a pharmaceutically acceptable carrier.

1 . A method of providing a safe and effective treatment of erythema or a symptom associated therewith in a subject, comprising topically administering to a skin area affected by the erythema or the symptom a topical composition comprising about 0.3% to about 10% by weight brimonidine and a pharmaceutically acceptable carrier, wherein the topical administration effects a serum or plasma profile of brimonidine having a mean C max  of about 54±28 pg/mL or less and a mean AUC 0-24hr  of about 568±277 pg.hr/mL or less. 
     
     
         2 . The method of  claim 1 , wherein the erythema is erythema of rosacea. 
     
     
         3 . The method of  claim 1 , further comprising administering to the subject at least one additional treatment and medication for erythema or the symptom associated therewith. 
     
     
         4 . The method of  claim 1 , wherein the topical composition is administered to the skin area once daily. 
     
     
         5 . The method of  claim 1 , wherein the topical administration of the topical composition to the skin area resulted in significantly more reduction of facial erythema associated with rosacea compared to a vehicle control as measured by a 12 hour success profile evaluated on both CEA and PSA scales, wherein the 12 hour success profile comprises a noticeable effect of 1-grade improvement of the erythema or the symptom and about 1 hour to about 8 hours of a 2-grade improvement of the erythema or the symptom. 
     
     
         6 . The method of  claim 5 , wherein the 12 hour success profile comprises a noticeable effect of 1-grade improvement of the erythema or the symptom and about 3 hours to about 6 hours of a 2-grade improvement of the erythema or the symptom. 
     
     
         7 . The method of  claim 1 , wherein the topical composition further comprises
 about 0.20% (w/w) to about 4.0% (w/w) gelling agent; and   about 5.0% (w/w) to about 30.0% (w/w) at least one polyol.   
     
     
         8 . The method of  claim 7 , wherein the topical composition comprises about 0.4% to about 0.6% by weight of brimonidine tartrate. 
     
     
         9 . The method of  claim 8 , wherein the topical composition comprises about 0.5% by weight of brimonidine tartrate. 
     
     
         10 . The method of  claim 7 , wherein the topical composition comprises about 0.50% (w/w) to about 2.0% (w/w) carbomer. 
     
     
         11 . The method of  claim 10 , wherein the carbomer is selected from the group consisting of carbomer 934P, Carbopol® 974P, and Carbopol® 980. 
     
     
         12 . The method of  claim 7 , wherein the topical composition further comprises about 0.04% to about 0.08% (w/w) water dispersible form of titanium dioxide. 
     
     
         13 . The method of  claim 7 , wherein the topical composition further comprises a preservative selected from the group consisting of sodium benzoate, phenoxyethanol, benzyl alcohol, methylparaben, imidazolidinyl urea and diazolidinyl urea. 
     
     
         14 . The method of  claim 7 , wherein the topical composition comprises at least one of glycerin and propylene glycol. 
     
     
         15 . A method of producing a packaged product for providing a safe and effective treatment of erythema or a symptom associated therewith in a subject, comprising:
 (1) obtaining a topical composition comprising about 0.3% to about 10% by weight brimonidine and a pharmaceutically acceptable carrier;   (2) devising instructions for topically administering the topical composition to a skin area affected by the erythema or the symptom to obtain the safe and effective treatment, and   (3) providing the topical composition and the instructions in a unified package, wherein the topical administration effects a serum or plasma profile of brimonidine having a mean C max  of about 54±28 pg/mL or less and a mean AUC 0-24hr  of about 568±277 pg.hr/mL or less.   
     
     
         16 . A topical gel composition for providing a safe and effective treatment of erythema or a symptom associated therewith in a subject, comprising:
 about 0.3% (w/w) to about 10.0% (w/w) brimonidine;   about 0.20% (w/w) to about 4.0% (w/w) gelling agent; and   about 5.0% (w/w) to about 30.0% (w/w) at least one polyol,   
       wherein the topical administration of the topical gel composition to a skin area affected by the erythema or the symptom effects a serum or plasma profile of brimonidine having a mean C max  of about 54±28 pg/mL or less and a mean AUC 0-24hr  of about 568±277 pg.hr/mL or less. 
     
     
         17 . The topical gel composition of  claim 16 , comprising about 0.4% to about 0.6% by weight of brimonidine. 
     
     
         18 . The topical gel composition of  claim 16 , comprising about 0.5% by weight of brimonidine tartrate. 
     
     
         19 . The topical gel composition of  claim 16 , comprising about 0.50% (w/w) to about 2.0% (w/w) carbomer. 
     
     
         20 . The topical gel composition of  claim 16 , comprising at least one of glycerin and propylene glycol.