Treatment and prevention of benign pigmented moles (naevi) using artemisinine and the derivatives thereof

Abstract

A method of treating a benign pigmented mole or a dermatomycosis. The method comprises locally applying to a subject in need thereof artemisinine and/or one or more structurally related compounds. Also disclosed is a plaster which comprises a topical formulation comprising artemisinine and/or one or more structurally related compounds.

1 . A plaster comprising a topical formulation which comprises one or more active agents, wherein the one or more active agents comprise at least one compound of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 X represents CO, CHOZ or CHNRZ; 
 Z is selected from hydrogen; straight-chain and branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; (C 7 -C 24 ) aralkyl; m- and p-CH 2 (C 6 H 4 )COOM; COR 3 ; CSR 3 ; C(NR 6 )R 3 ; SOR 4 ; SO 2 OM; SO 2 NR 7 R 8 ; SO 2 O-artemisinyl; SO 2 NH-artemisinyl; POR 4 R 5 ; and PSR 4 R 5 ; 
 R 3  is selected from straight-chain or branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 1 -C 6 ) alkoxy; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; (C 6 -C 10 ) aryloxy; (C 7 -C 24 ) aralkyl; —(CH 2 ) n —COOM, with n being an integer of from 1 to 6; and 10α-di-hydro artemisinyl; 
 R 4  and R 5  are independently selected from straight-chain or branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; (C 7 -C 24 ) aralkyl; OM; straight-chain or branched (C 1 -C 6 ) alkoxy; (C 6 -C 10 ) aryloxy; and NR 7 R 8 ; 
 R 6  is selected from straight-chain or branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; and (C 7 -C 24 ) aralkyl; 
 M represents hydrogen or a pharmaceutically acceptable cation; 
 R 7  and R 8  are independently selected from straight-chain or branched (C 1 -C 6 ) alkyl, or R 7  and R 8  together form a (C 4 -C 6 ) alkylene bridge; and 
 R is selected from hydrogen; straight-chain or branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; and (C 7 -C 24 ) aralkyl. 
 
     
     
         2 . The plaster of  claim 1 , wherein X represents CHOZ, Z is selected from m- and p-CH 2 (C 6 H 4 )COOM and COR 3 ; and R 3  represents —(CH 2 ), —COOM. 
     
     
         3 . The plaster of  claim 1 , wherein the one or more compounds of formula (I) comprise at least one compound selected from artemisinine; dihydroartemisinine; carboxyl group containing derivatives of formula (I); artemether; arteether; propyl carbonate of dihydroartemisinine, and artelinic acid. 
     
     
         4 . The plaster of  claim 1 , wherein the one or more compounds of formula (I) comprise at least one compound selected from artemisinine, dihydroartemisinine, and artesunate. 
     
     
         5 . The plaster of  claim 1 , wherein the one or more compounds of formula (I) comprise artesunate. 
     
     
         6 . The plaster of  claim 1 , wherein the topical formulation comprises at least one of a paste, an ointment, a suspension, a solution, a gel, a spray, and a cream. 
     
     
         7 . A method of treating a benign pigmented mole or a dermatomycosis, wherein the method comprises locally applying to a subject in need thereof one or more compounds of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 X represents CO, CHOZ or CHNRZ; 
 Z is selected from hydrogen; straight-chain and branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; (C 7 -C 24 ) aralkyl; m- and p-CH 2 (C 6 H 4 )COOM; COR 3 ; CSR 3 ; C(NR 6 )R 3 ; SOR 4 ; SO 2 OM; SO 2 NR 7 R 8 ; SO 2 O-artemisinyl; SO 2 NH-artemisinyl; POR 4 R 5 ; and PSR 4 R 5 ; 
 R 3  is selected from straight-chain or branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 1 -C 6 ) alkoxy; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; (C 6 -C 10 ) aryloxy; (C 7 -C 24 ) aralkyl; —(CH 2 ) n —COOM, with n being an integer of from 1 to 6; and 10α-di-hydroartemisinyl; 
 R 4  and R 5  are independently selected from straight-chain or branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; (C 7 -C 24 ) aralkyl; OM; straight-chain or branched (C 1 -C 6 ) alkoxy; (C 6 -C 10 ) aryloxy; and NR 7 R 8 ; 
 R 6  is selected from straight-chain or branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; and (C 7 -C 24 ) aralkyl; 
 M represents hydrogen or a pharmaceutically acceptable cation; 
 R 7  and R 8  are independently selected from straight-chain or branched (C 1 -C 6 ) alkyl, or R 7  and R 8  together form a (C 4 -C 6 ) alkylene bridge; and 
 R is selected from hydrogen; straight-chain or branched (C 1 -C 6 ) alkyl; straight-chain or branched (C 2 -C 6 ) alkenyl; straight-chain or branched (C 2 -C 6 ) alkynyl; (C 3 -C 8 ) cycloalkyl; (C 6 -C 24 ) aryl; and (C 7 -C 24 ) aralkyl. 
 
     
     
         8 . The method of  claim 7 , wherein the topical formulation is applied in conjunction with a plaster. 
     
     
         9 . The method of  claim 7 , wherein mycosis pedis or nail fungus is treated. 
     
     
         10 . The method of  claim 7 , wherein the method further comprises a prevention of cancer. 
     
     
         11 . The method of  claim 7 , wherein the one or more compounds of formula (I) comprise at least one compound wherein X is CHOZ, Z is selected from m- and p-CH 2 (C 6 H 4 )COOM and COR 3 ; and R 3  represents —(CH 2 ) n —COOM. 
     
     
         12 . The method of  claim 7 , wherein the one or more compounds of formula (I) comprise at least one compound selected from artemisinine; dihydroartemisinine; carboxyl group containing derivatives of formula (I); artemether; arteether; propyl carbonate of dihydroartemisinine, and artelinic acid. 
     
     
         13 . The method of  claim 7 , wherein the one or more compounds of formula (I) comprise at least one compound selected from artemisinine, dihydroartemisinine, and artesunate. 
     
     
         14 . The method of  claim 7 , wherein the one or more compounds of formula (I) comprise artesunate. 
     
     
         15 . The method of  claim 7 , wherein the one or more compounds of formula (I) are applied in a form of a topical formulation. 
     
     
         16 . The method of  claim 15 , wherein the topical formulation comprises at least one of a paste, an ointment, a suspension, a solution, a gel, a spray, and a cream. 
     
     
         17 . The method of  claim 16 , wherein the topical formulation comprises an ointment and loss of moisture from skin is prevented by application of the ointment.