Peptides and peptide derivatives as well as pharmaceutical compositions containing the same

Abstract

Therapeutic compositions can include modified peptides which are derived from the chain of the Bbeta(15-42)-fibrin fragment and wherein one or several of the amino acids of the sequence have been substituted by genetically encoded or not genetically encoded amino acids or peptidomimetics. They may exist as free peptides or as C-terminal derivative and/or being linked to a polyethylene glycol (PEG)-polymer, and have anti-inflammatory and/or endothelium stabilizing effects. Esters or amides may for instance be taken into consideration as C-terminal derivatives. Processes for production of the peptides and derivatives thereof are also described.

1 - 7 . (canceled) 
     
     
         8 . A peptide of Formula II: 
       
         
           
                 
               
                   (SEQ ID NO: 9) 
                 
                 
                 
               
                     
                   H 2 N-GHRPLDKKREEAPSLRPAPPPISGGGYR-X 17   
                 
             
                
               
            
             
                
               
            
           
         
         or a physiologically acceptable salt thereof, wherein X 17  denotes NR 2 R 3 , R 2  and R 3  being identical or different and denoting hydrogen, (C 1 -C 10 )-alkyl, or a residue-PEG 5-40K , wherein the PEG-residue is linked to the N atom via a spacer. 
       
     
     
         9 . The peptide of  claim 8 , wherein X 17  denotes NR 2 R 3 , R 2  and R 3  being identical and denoting hydrogen. 
     
     
         10 . A pharmaceutical composition, comprising the peptide of  claim 8  and a pharmaceutically acceptable additive. 
     
     
         11 . A peptide of Formula II: 
       
         
           
                 
               
                   (SEQ ID NO: 67) 
                 
                 
                 
               
                     
                   H 2 N-GHRPLDKKREEAPSLRPAPPPISGGGYR-X 17   
                 
             
                
               
            
             
                
               
            
           
         
         or a physiologically acceptable salt thereof, wherein X 17  denotes a residue C(NR 2 R 3 )—(S-succinimido)-(PEG 5-60K ), R 2  and R 3  being identical and denoting hydrogen, and the succinimido residue being linked to the sulfur atom of the cysteine residue via C-atom 3, or a physiologically acceptable salts thereof. 
       
     
     
         12 . The peptide of  claim 12 , wherein PEG is 20K. 
     
     
         13 . A pharmaceutical composition, comprising the peptide of  claim 11  and a pharmaceutically acceptable additive. 
     
     
         14 . A method for preventing or treating Acute Respiratory Distress Syndrome in an individual comprising administering to the individual an effective amount of the peptide of  claim 8 . 
     
     
         15 . A method for preventing or treating Acute Respiratory Distress Syndrome in an individual comprising administering to the individual an effective amount of the peptide of  claim 11 . 
     
     
         16 . A method for preventing or treating Systemic Inflammatory Response Syndrome in an individual comprising administering to the individual an effective amount of the peptide of  claim 8 . 
     
     
         17 . A method for preventing or treating Systemic Inflammatory Response Syndrome in an individual comprising administering to the individual an effective amount of the peptide of  claim 11 . 
     
     
         18 . A method for preventing or treating shock in an individual comprising administering to the individual an effective amount of the peptide of  claim 8 . 
     
     
         19 . A method for preventing or treating shock in an individual comprising administering to the individual an effective amount of the peptide of  claim 11 . 
     
     
         20 . A method for preventing or treating reperfusion trauma in an individual comprising administering to the individual an effective amount of the peptide of  claim 8 . 
     
     
         21 . A method for preventing or treating reperfusion trauma in an individual comprising administering to the individual an effective amount of the peptide of  claim 11 . 
     
     
         22 . A method for preventing or treating Dengue virus in an individual comprising administering to the individual an effective amount of the peptide of  claim 8 . 
     
     
         23 . A method for preventing or treating Dengue virus in an individual comprising administering to the individual an effective amount of the peptide of  claim 11 . 
     
     
         24 . A method for preventing or treating organ failure in an individual comprising administering to the individual an effective amount of the peptide of  claim 8 . 
     
     
         25 . A method for preventing or treating organ failure in an individual comprising administering to the individual an effective amount of the peptide of  claim 11 .