Peptides of use in the preventive and curative treatment of alopecia

Abstract

The object of the present invention relates to a novel family of peptide conjugates of formula (I):A-X1—X2-Pro-Ala-X—B   (I)wherein:A represents a hydrogen atom, a C6 to C20 acyl group or a cholesterol residue;X1 represents a covalent bond, an alanine or a proline;X2 represents an arginine, a lysine, or an alanine;X represents a lysine, an alanine, or a phenylalanine; andB represents a hydroxyl or an amine;or one of its preferentially pharmaceutically, dermatologically or cosmetically acceptable salts,as well as their synthesis processes and their uses for reducing hair loss and stimulating hair growth.

1 .- 16 . canceled 
     
     
         17 . A method for the treatment of alopecia in a person in need thereof, said method comprising administering to said person a peptide conjugate of formula (I):
   A-X 1 —X 2 -Pro-Ala-X—B   (I)
   wherein:
 A represents a hydrogen atom, a C 6  to C 20  acyl group or a cholesterol residue; 
 X 1  represents a covalent bond, an alanine or a proline; 
 X 2  represents an arginine, a lysine, or an alanine; 
 X represents a lysine, an alanine, or a phenylalanine; and 
 B represents a hydroxyl or an amine; 
 or one of its preferentially pharmaceutically, dermatologically, or cosmetically acceptable salts, wherein the peptide conjugate is not Palm-Ala-Ala-Pro-Ala-Lys-NH 2  (SEQ ID NO:6), Palm being a palmitoyl group. 
   
     
     
         18 . The method according to  claim 17 , wherein group A represents a hydrogen atom, a C 10  to C 18  acyl group, or a cholesterol residue according to formula (II): 
       
         
           
           
               
               
           
         
         wherein: 
         Y represents the carbon atom of the ester bond between the cholesterol residue and X 1 . 
       
     
     
         19 . The method according to  claim 17 , wherein the salt is an acid addition salt. 
     
     
         20 . The method according to  claim 17 , wherein X 1  is an alanine or a covalent bond, and X 2  is an arginine or an alanine. 
     
     
         21 . The method according to  claim 17 , wherein the peptide conjugate of formula (I) is selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   H-Ala-Arg-Pro-Ala-Lys-OH, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   Palm-Ala-Arg-Pro-Ala-Lys-OH, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   Palm-Ala-Arg-Pro-Ala-Lys-NH 2 , 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   Palm-Ala-Arg-Pro-Ala-Ala-NH 2 , 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   Chol-Ala-Arg-Pro-Ala-Lys-NH 2 , 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   H-Arg-Pro-Ala-Lys-OH, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   Palm-Arg-Pro-Ala-Lys-OH, 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and wherein
 Palm represents a palm itoyl group and Chol represents a cholesterol residue. 
 
     
     
         22 . The method according to  claim 17 , wherein the peptide conjugate of formula (I) is used in combination with another dermatologically-active ingredient. 
     
     
         23 . The method of  claim 22 , wherein said dermatologically-active ingredient is minoxidil, a nicotinic acid ester, a 5α-reductase inhibitor, another peptide with dermatological activity, or combinations thereof. 
     
     
         24 . The method according to  claim 17 , wherein the alopecia is selected from androgenetic, congenital, acquired, localized, diffuse, acute, and chronic alopecia. 
     
     
         25 . The method according to  claim 18 , wherein said C 10  to C 18  acyl group is a palmitoyl group. 
     
     
         26 . A pharmaceutical, dermatological, or cosmetic composition comprising at least one peptide conjugate of formula (I):
   A-X 1 —X 2 -Pro-Ala-X—B   (I)
   wherein:   A represents a hydrogen atom, a C 6  to C 20  acyl group or a cholesterol residue;   X 1  represents a covalent bond, an alanine or a proline;   X 2  represents an arginine, a lysine, or an alanine;   X represents a lysine, an alanine, or a phenylalanine; and   B represents a hydroxyl or an amine;   or one of its preferentially pharmaceutically, dermatologically, or cosmetically acceptable salts, wherein the peptide conjugate is not Palm-Ala-Ala-Pro-Ala-Lys-NH 2  (SEQ ID NO:6), Palm being a palmitoyl group.   
     
     
         27 . The composition according to  claim 26 , further characterized in that it is a composition for topical use. 
     
     
         28 . The composition according to  claim 26 , wherein said composition comprises the peptide conjugate of formula (I) in the form of enantiomers and/or of diastereoisomers. 
     
     
         29 . The composition according to  claim 26 , characterized in that it is a composition for the scalp. 
     
     
         30 . The composition according to  claim 26 , wherein said composition is a lotion, a serum, a shampoo, a spray, a gel, or a cream. 
     
     
         31 . The composition according to  claim 30 , wherein said shampoo is a medicated shampoo. 
     
     
         32 . The composition according to  claim 26 , wherein the concentration of the peptide conjugate of formula (I) ranges between 10-9 and 10-4 mole/litre of composition.