Treatment of connective tissue diseases of the skin

Abstract

The present invention provides effective and safe medicaments for the treatment of connective tissue diseases of the skin, particularly with respect to the treatment of cutaneous forms of Lupus Erythematous. The medicaments comprise as the therapeutically active ingredient a beta 2 adrenoceptor agonist. The invention furthermore relates to dermatological compositions without skin sensitization properties and which contain enantiomerically pure or enriched R-enantiomers of a beta 2 adrenoceptor agonist.

1 . A topically administrable pharmaceutical composition comprising as the therapeutically active ingredient a beta 2 -adrenoceptor agonist according to formula II or a physiologically acceptable derivative thereof or a pharmaceutically acceptable salt thereof, wherein the carbon atom at C 1  designate an asymmetric carbon having R-configuration 
       
         
           
           
               
               
           
         
         wherein the terms Z, X, and Y independently designate radicals selected from the group consisting of H; substituted C 1-6 -alkyl, C 4-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkoxyl, phenyl, C 7-14  alkaryl and C 7-14  alkheterocyclyl; OOR′, CN, NH—CO—NH2, NH—CO, trihalogenmethyl, halogen, OH, OR′, NH 2 , NHR′, NR′R″, CO, CO—R′, HSO 2 , R′—SO 2 , NH—SO 2 —R′ and wherein two of the groups selected from Z, X and Y together form a 5 or 6 membered carbon ring or a carbon ring with one nitrogen atom (N) in the ring; 
       
       the terms R 1  and R 2  independently designate a radical selected from the group consisting of H, C 1-6 -alkyl, C 4-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkoxyl, C 7-14  alkaryl, C 7-14  alkheterocyclyl, and wherein R 1  and R 2  together form a 5 or 6 membered carbon ring or a carbon ring with one nitrogen atom (N) in the ring; 
       the term R 3  designate a radical selected from the group consisting of H, halogen, C 1-6 -alkyl, C 4-6 -cycloalkyl, C 2-6 -alkenyl and C 2-6 -alkynyl; 
       the groups, C 1-6 -alkyl, C 4-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkoxyl, C 7-14  alkaryl, and C 7-14  alkheterocyclyl is mono or di-substituted with NH 2 , NHR′, NR′R″, OH, cyano, nitro and halogen; and 
       the terms R′ and R″ independently designate a radical selected from the group consisting of C 1-6 -alkyl, C 4-6 -cycloalkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 1-6 -alkoxyl, C 7-14  alkaryl and C 7-14  alkheterocyclyl; 
       and wherein the composition further comprises one or more dermatologically acceptable excipients or carriers. 
     
     
         2 . The composition according to  claim 1 , wherein the beta 2 -adrenoceptor agonist is selected from enantiomerically pure or enantiomerically enriched R-enantiomer of Amiterol, Bamethan, Bitolterol, Butaxamine, Carbuterol, Cimaterol, Colterol, Clenbuterol, Clorprenaline, Colterol, Deterenol, Dioxethedrin, Etafedrine, Ethylnorepinephrine, Fenoterol, Indacaterol, Isoproterenol, Mabuterol, Meluadrine, Nardeterol, Norbudrine, Norepinephrine, Orciprenaline, Picumeterol, Pirbuterol, Quinprenaline, Reproterol, Salbutamol, Salmeterol, Soterenol, Sulfonterol, Terbutaline, Tulobuterol, Zinterol, a physiologically acceptable derivative thereof and a pharmaceutically acceptable salt thereof. 
     
     
         3 . The composition according to  claim 1 , wherein the beta 2 -adrenoceptor agonist is selected from diastereomeric pure or diastereomeric enriched RR or RS isomer of a beta 2 -adrenoceptor agonist selected from Flerobuterol, Formoterol, Hexoprenaline, Isoetarine, Medroxalol, Procaterol, Protokylol, Rimiterol, Salmefamol, Zilpaterol, a physiologically acceptable derivative thereof and a pharmaceutically acceptable salt thereof. 
     
     
         4 . The composition according to  claim 1 , wherein the beta 2 -adrenoceptor agonist is R-salbutamol, a physiologically acceptable derivative thereof or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The composition according to  claim 1 , wherein the topically administrable composition is formulated for topical application to skin. 
     
     
         6 . The composition according to  claim 5 , wherein the topically administrable composition is formulated as an emulsion, a gel, a solution, a liniment, an ointment, a foam, a topical spray for skin, or a powder. 
     
     
         7 . The composition according to  claim 1 , wherein the beta 2 -adrenoceptor agonist is in an amount ranging between 0.01 and 10% by weight. 
     
     
         8 . The composition according to  claim 1 , wherein the beta 2 -adrenoceptor agonist is in an amount ranging between 0.05 and 5% by weight. 
     
     
         9 . The composition according to  claim 1 , wherein the beta 2 -adrenoceptor agonist is in an amount ranging between 0.2 and 2.5% by weight. 
     
     
         10 . The composition according to  claim 1 , with the proviso that the composition does not contain a substantial amount of a corticosteroid. 
     
     
         11 . The composition according to  claim 10 , with the proviso that the composition does not contain an aminosugar. 
     
     
         12 . The composition according to  claim 1 , wherein the beta 2 -adrenoceptor agonist is the sole therapeutically active ingredient in the composition.