Compounds, Formulations and Methods for Reducing Skin Wrinkles, Creasing and Sagging

Abstract

Methods, compounds, and topical formulations for reduction of skin sagging, creasing and/or wrinkling are disclosed. The methods comprise topically applying a composition comprising an α2 adrenergic receptor agonist. Amelioration of skin sagging, creasing and/or wrinkling begins within minutes after topical application of a disclosed composition. A single application can significantly reduce skin sagging, creasing and/or wrinkling for at least about 8 hours.

1 . A method of reducing skin sagging, creasing and/or wrinkling, the method comprising topically administering to the sagging, creasing, and/or wrinkling skin of a person in need of treatment a composition comprising at least one of an α 2  adrenergic receptor agonist and a pharmaceutically acceptable salt thereof, in an amount effective for amelioration of skin sagging, creasing and/or wrinkling. 
   
   
       2 . The method according to  claim 1  wherein the at least one α 2  adrenergic receptor agonist is selected from the group consisting of the compounds shown below: 
     
       
         
         
             
             
         
       
     
     wherein each of R 1 , R 2 , and R 3  is independently hydrogen, halogen, 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 at least one α 2  adrenergic receptor agonist is selected from the group consisting of brimonidine, naphazoline, tetrahydrozaline, oxymetazoline, xylometazoline, epinephrine, norepinephrine, phenylephrine, and methoxamine. 
   
   
       4 . The method according to  claim 1 , wherein the at least one α 2  adrenergic receptor agonist is a reversible α 2  adrenergic receptor agonist. 
   
   
       5 . The method according to  claim 1 , wherein the composition further comprises at least one pharmaceutically acceptable carrier. 
   
   
       6 . The method according to  claim 5 , wherein the composition is of a form selected from the group consisting of a spray, a mist, an aerosol, a lotion, a gel, a cream, an ointment, a foam, a paste, an unguent, an emulsion, a liposomal suspension, a colloid and a combination thereof. 
   
   
       7 . The method according to  claim 5 , wherein the composition further comprises a cosmetic, a foundation, a moisturizer and a sun-blocking agent. 
   
   
       8 . The method according to  claim 1 , wherein the amount of composition applied to the affected area ranges from about 0.1 g/cm 2  to about 5 g/cm 2  of skin surface area. 
   
   
       9 . The method according to  claim 1 , wherein the composition further comprises at least one second active ingredient selected from the group consisting of azelaic acid, benzoyl peroxide, isotretinoin, an antibiotic, a chemically modified antibiotic, a pharmaceutically acceptable salt thereof and a combination thereof, in an amount effective for amelioration of skin sagging, creasing and/or wrinkling. 
   
   
       10 . The method according to  claim 9 , wherein the antibiotic is selected from the group consisting of clindamycin, doxycycline, erythromycin, metronidazole, sulfacetamide, and tetracycline. 
   
   
       11 . The method according to  claim 1 , further comprising systemically administering an antibiotic in an amount effective for treatment of skin sagging, creasing and/or wrinkling. 
   
   
       12 . The method according to  claim 11 , wherein the antibiotic is selected from the group consisting of clindamycin, doxycycline, erythromycin, metronidazole, sulfacetamide, and tetracycline. 
   
   
       13 . The method according to  claim 1 , wherein an amount effective for amelioration of skin sagging, creasing and/or wrinkling is an amount which ameliorates skin sagging, creasing and/or wrinkling within about 5 minutes after the administering. 
   
   
       14 . The method according to  claim 1 , wherein an amount effective for amelioration of skin sagging, creasing and/or wrinkling is an amount which ameliorates skin sagging, creasing and/or wrinkling for at least about 8 hours. 
   
   
       15 . The method according to  claim 14 , wherein an amount effective for amelioration of skin sagging, creasing and/or wrinkling is an amount which ameliorates skin sagging, creasing and/or wrinkling for up to about 12 hours. 
   
   
       16 . The method according to  claim 14 , wherein an amount effective for amelioration of skin sagging, creasing and/or wrinkling is an amount which ameliorates skin sagging, creasing and/or wrinkling for up to about 18 hours. 
   
   
       17 . The method according to  claim 14 , wherein an amount effective for amelioration of skin sagging, creasing and/or wrinkling is an amount which ameliorates skin sagging, creasing and/or wrinkling for up to about 24 hours.