Injectable formulation for treatment and protection of patients having an inflammatory reaction or an ischemia-reperfusion event

Abstract

Compounds according to formula (I) are particularly suitable for the treatment and/or prevention of a medical condition involving hypoxic, anoxic and/or inflamed mammalian tissue. Furthermore, the invention relates to the use of said compounds for preparing a medicament and to pharmaceutical preparations comprising such compounds. The invention also relates to methods of treating or protecting patients having or being prone to develop a medical condition involving hypoxic, anoxic and/or inflamed mammalian tissue, the methods comprising administration of a therapeutically effective amount of such compounds

1 - 18 . (canceled) 
     
     
         19 . A method for treating or inhibiting a condition selected form the group consisting of ischemia reperfusion injury, severe inflammatory response syndrome, sepsis, organ transplantation, organ resection, organ rejection, inflammation, surgery and catheterization, the method comprising the administration of a pharmaceutical composition comprising a compound of formula (I):
   (R 1 ) n —R 2 —(C[[(R 3 ) 2 ]]F   3   ) m    (I),
   wherein:   n is 1 to 5,   m is 1 to 5,   R 1  denotes in each instance a functional group bound to R 2 , wherein each R 1  is independently selected from the group consisting of —OH, —NH 2 , —COON, —COOR 4 , —CHO, —C(O)—R 4 , —CONH 2 , and —CONHR 4 ;   R 2  denotes a linear or branched, substituted or non-substituted C 1-15  alkyl, the substituent being selected independently from the group consisting of —F, —Cl, —Br, —I, —OH, —NH 2 , —COON, —COOR 4 , —CHO, —C(O)—R 4 , —CONH 2 , and —CONHR 4 ; and   R 4  denotes a linear or branched, substituted or unsubstituted C 1-10  alkyl;   as well as their diastereomers or enantiomers in the form of their acids, bases or salts of physiologically acceptable acids or bases.   
     
     
         20 . The method according to  claim 19 , wherein R 2  is a linear or branched, non-substituted C 1-15  alkyl . 
     
     
         21 . The method according to of  claim 19 , wherein R 2  is a linear or branched C 1-15  alkyl substituted with 1 to 10 substituents, each substituent being selected independently from the group consisting of —F, —Cl, —Br, —I, —OH, —NH 2 , —COOH, —COOR 4 , —CHO, —C(O)—R 4 , —CONH 2 , and —CONHR 4 , wherein R 4  is defined as in  claim 19 . 
     
     
         22 . The method according to  claim 19 , wherein R 2  is a linear or branched, non-substituted C 1-4  alkyl. 
     
     
         23 . The method according to  claim 19 , wherein R 2  is a linear or branched C 1-4  alkyl substituted with 1 to 10 substituents, each substituent being selected independently from the group consisting of —F, —Cl, —Br, —I, —OH, —NH 2 , —COOH, —COOR 4 , —CHO, —C(O)—R 4 , —CONH 2 , and —CONHR 4 , wherein R 4  is defined as in  claim 19 . 
     
     
         24 . The method according to  claim 19 , wherein R 2  is substituted with 1 to 3 substituents. 
     
     
         25 . The method according  claim 19 , wherein R 4  is methyl in each instance. 
     
     
         26 . The method according to  claim 19 , wherein n is 1. 
     
     
         27 . The method according to  claim 19 , wherein m is 1 or 2. 
     
     
         28 . The method according to  claim 19 , wherein said compound has fewer than 7 carbon atoms. 
     
     
         29 . The method according to  claim 19 , wherein each R 1  is —OH. 
     
     
         30 . The method according to  claim 19 , wherein said compound is selected from the group consisting of
 1,1,1,3,3,3-hexafluoro-2-methyl-2-propanol,   2,2,3,4,4,4-hexafluoro-1-butanol,   perfluoro-tert-butyl alcohol,   2,2,3,3,3-pentafluoro-1-propanol,   1,1,1,3,3,4,4,4-octafluoro-2-butanol,   2,2,3,3,4,4,4-heptafluoro-1-butanol,   1,1,1,3,3,3-hexafluoropropan-2-ol,   2,2,2-trifluoroethanol,   3,4,4,4-tetrafluoro-3-(trifluoromethyl)butan-1-ol,   2-(2,2,3,4,4,4-hexafluorobutoxy)ethanol,   3-amino-4,4,4-trifluorobutyric acid,   3,3,3-trifluoro-2-(hydroxymethyl)propanoic acid and   5,5,5-trifluorleucine.   
     
     
         31 . The method according to  claim 19 , wherein said compound has an octanol-water partition coefficient of less than 20. 
     
     
         32 . The method according to  claim 19 , wherein said compound is inhalatively administered. 
     
     
         33 . The method according to  claim 19 , wherein said compound is administered prior to, after or concomitantly to said ischemia reperfusion injury, severe inflammatory response syndrome, sepsis, organ transplantation, organ resection, organ rejection, inflammation, surgery or catheterization. 
     
     
         34 . A pharmaceutical composition, comprising at least one compound according to  claim 19 . 
     
     
         35 . The pharmaceutical composition of  claim 34 , further comprising one or more physiologically acceptable excipients. 
     
     
         36 . The pharmaceutical composition of  claim 34 , wherein said composition is formulated for inhalative administration. 
     
     
         37 . A medical device, comprising at least one surface coated with at least one of the compounds according to  claim 19 . 
     
     
         38 . The medical device of  claim 37 , wherein said device is an implant or organ transplant. 
     
     
         39 . The medical device of  claim 37 , wherein said device is selected from the group consisting of bone, tooth and cartilage implants, syringes, catheters, electrodes, stents and cardiac pacemakers.