Topical compositions and methods for skin lightening

Abstract

Embodiments of the invention are generally directed to compositions useful for reducing pigmentation in the skin. The composition may further include other depigmenting agents such as nicotinamide and its melanasome transfer-inhibiting derivatives, 3,3′-thiodipropanoic acid and its tyrosinase-inhibiting derivatives, or resorcinol and its tyrosinase-inhibiting derivatives, in a topically acceptable vehicle.

1 . A topical composition comprising, in a topically acceptable vehicle, an effective amount of a compound having the structure of formula (I): 
       
         
           
           
               
               
           
         
         wherein, R N  are independently selected at each occurrence from hydrogen or C 1- C 12  hydrocarbons, optionally containing from 1-8 heteroatoms selected from halogen, O, N, and S and combinations thereof; and wherein two groups R N  on the same nitrogen atom may together form a three- to six-membered ring; 
         R a  is independently selected from hydrogen, —F; —Cl; —Br; —I; —OH, —OR*; —NH 2 ; —NHR*; —N(R*) 2 ; —N(R*) 3   + ; —N(R*)—OH; —N(→O)(R*) 2 ; —O—N(R*) 2 ; —N(R*)—O—R*; —N(R*)—N(R*) 2 ; —C═N—R*; —N═C(R*) 2 ; —C═N—N(R*) 2 ; —C(═NR*)—N(R*) 2 ; —SH; —SR*; —CN; —NC; —(C═O)—R*; —CHO; —CO 2 H; —CO 2   − ; —CO 2 R*; —(C═O)—S—R*; —O—(C═O)—H; —O—(C═O)—R*; —S—(C═O)—R*; —(C═O)—NH 2 ; —(C═O)—N(R*) 2 ; —(C═O)—NHNH 2 ; —O—(C═O)—NHNH 2 ; —(C═S)—NH 2 ; —(C═S)—N(R*) 2 ; —N(R*)—CHO; —N(R*)—(C═O)—R*; —(C═NR)—O—R*; —O—(C═NR*)—R*, —SCN; —NCS; —NSO; —SSR*; —N(R*)—C(═O)—N(R*) 2 ; —N(R*)—C(═S)—N(R*) 2 ; —SO 2 —R*; —O—S(═O) 2 —R*; —S(═O) 2 —OR*; —N(R*)—SO 2 —R*; —SO 2 —N(R*) 2 ; —O—SO 3   − ; —O—S(═O) 2 —OR*; —O—S(═O)—OR*; —O—S(═O)—R*; —S(═O)—OR*; —S(═O)—R*; —NO; —NO 2 ; —NO 3 ; —O—NO; —O—NO 2 ; —N 3 ; —N 2 —R*; —N(C 2 H 4 ); —Si(R*) 3 ; —CF 3 ; —O—CF 3 ; —PR* 2 ; —O—P(═O)(OR*) 2 ; —P(═O)(OR*) 2 ; C 1 -C 8  perfluoroalkyl; an aliphatic C 1 -C 8  hydrocarbon radical; a C 1 -C 8  aromatic hydrocarbon radical; or a C 1 -C 8  heteroaryl radical; 
         X 1  and X 2  are independently selected from oxygen, sulfur, NR N , or CR*R*; 
         R* is independently at each occurrence hydrogen or a straight chained, branched, or cyclic C 1 -C 20  hydrocarbon radical, optionally substituted with one or more groups R a  or with 1-6 heteroatoms selected from nitrogen, oxygen, sulfur, or halogen and combinations thereof; 
         ring “A” is a five or six-membered optionally aromatic ring, z 1  is —C—, —N—, —NL 1 -, or —CL 1 -; and z 2 -z 6  are independently selected from —N—, —NH—, —NR*—, —O—, —S—, —CH—, —CR—, —CR*—, and in the case where ring “A” is a five membered ring, z 4  is a bond (i.e., it is absent); where L 1  is group —X a —(CH 2 ) r —(CH═CH) s —X b —(CH 2 ) y —(CH═CH) z —X c —, where X a , X b , and X c  are independently a bond (i.e., absent), —O—, —S—, —NH—, —NR*— and “r,” “s,” “y,” and “z” are independently at each occurrence integers from 0-2; 
         Z is selected from R*, OH, OR*, or NR N R N , wherein R N  and R* are as defined above; 
         and n and m are independently integers from 0-6; 
         and topically acceptable salts thereof. 
       
     
     
         2 . The composition according to  claim 1 , wherein said topically acceptable vehicle comprises a water-in-oil, oil-in-water, silicone-in-water, or water-in-silicone emulsion and further comprises an emulsifier. 
     
     
         3 . The composition according to  claim 1 , wherein said effective amount is from about 0.0001% to about 5% by weight based on the total weight of the composition. 
     
     
         4 . The composition according to  claim 1 , further comprising a retinoid in an amount from about 0.001% to about 5% by weight based on the total weight of the composition. 
     
     
         5 . The composition according to  claim 1 , further comprising at least one other ingredient selected from a film forming polymer, a thickener, a pH adjuster, a preservative, an emulsifier, a gelling agent, an antioxidant, an emollient, a humectant, a fragrance, and a colorant. 
     
     
         6 . The composition according to  claim 1 , further comprising at least one other depigmenting agent selected from nicotinamide, 3,3′-thiodipropanoic acid, dilauryl thiodipropionate, Kojic acid, hydroquinone, salicylic acid, and resorcinol. 
     
     
         7 . A topical composition comprising, in a topically acceptable vehicle, an effective amount of a compound having the structure of formula (II): 
       
         
           
           
               
               
           
         
         and cosmetically acceptable salts thereof. 
       
     
     
         8 . The composition according to  claim 7 , wherein said topically acceptable vehicle comprises a water-in-oil, oil-in-water, silicone-in-water, or water-in-silicone emulsion and further comprises an emulsifier. 
     
     
         9 . The composition according to  claim 7 , wherein said effective amount is from about 0.0001% to about 5% by weight based on the total weight of the composition. 
     
     
         10 . The composition according to  claim 7 , further comprising a retinoid in an amount from about 0.001% to about 5% by weight based on the total weight of the composition. 
     
     
         11 . The composition according to  claim 7 , further comprising at least one other ingredient selected from a film forming polymer, a thickener, a pH adjuster, a preservative, an emulsifier, a gelling agent, an antioxidant, an emollient, a humectant, a fragrance, and a colorant. 
     
     
         12 . The composition according to  claim 7 , further comprising at least one other depigmenting agent selected from nicotinamide, 3,3′-thiodipropanoic acid, dilauryl thiodipropionate, Kojic acid, hydroquinone, salicylic acid, and resorcinol. 
     
     
         13 - 18 . (canceled)