Compounds for the photodecontamination of pathogens in blood

Abstract

Psoralen compounds are synthesized which have substitutions on the 4, 4′, 5′, and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion.

We claim:  
     
         1 . A composition comprising: 
 a) a psoralen compound of the following formula;                          wherein R 1  is 
 —(CH 2 ) w —O—(CH 2 ) z —NH 2 ,  
 —(CH 2 ) w —R 2 —(CH 2 ) x —R 3 —(CH 2 ) z —NH 2 , or  
 —(CH 2 ) w —R 2 —(CH 2 ) x —R 3 —(CH 2 ) y —R 4 —(CH 2 ) z —NH 2 ,  
   wherein R 2 , R 3 , and R 4  are independently selected from the group consisting of O and NH, w is a whole number from 1 to 5, x is a whole number from 2 to 5, y is a whole number from 2 to 5, and z is a whole number from 2 to 6, and wherein R 5 , R 6 , and R 7  are independently selected from the group consisting of H and (CH 2 ) v CH 3  and v is a whole number from 0 to 5, or salts thereof; and    b) a blood product suitable for in vivo use.    
     
     
         2 . The composition of  claim 1 , wherein said blood product comprises plasma.  
     
     
         3 . The composition of  claim 2 , wherein said psoralen compound is at a concentration of between approximately 0.1 and 250 μM.  
     
     
         4 . The composition of  claim 1 , wherein said blood product comprises platelets.  
     
     
         5 . The composition of  claim 4 , further comprising a synthetic medium.  
     
     
         6 . The composition of  claim 5 , wherein said synthetic medium comprises sodium acetate.  
     
     
         7 . The composition of  claim 5 , wherein said synthetic medium comprises sodium chloride.  
     
     
         8 . The composition of  claim 5 , wherein said synthetic medium comprises sodium citrate.  
     
     
         9 . The composition of  claim 5 , wherein said synthetic medium comprises sodium phosphate.  
     
     
         10 . The composition of  claim 5 , wherein said synthetic medium comprises sodium acetate, sodium chloride, sodium citrate and sodium phosphate.  
     
     
         11 . The composition of  claim 10 , wherein said psoralen compound is at a concentration of between approximately 0.1 and 250 μM.  
     
     
         12 . A composition comprising: 
 a) a psoralen compound of the following formula:                          wherein R 5  is    —(CH 2 ) u —NH 2 ,    —(CH 2 ) w —R 2 —(CH 2 ) z —NH 2 ,    —(CH 2 ) w —R 2 —(CH 2 ) x —R 3 —(CH 2 ) z —NH 2 , or    —(CH 2 ) w —R 2 —(CH 2 ) x —R 3 —(CH 2 ) y —R 4 —(CH 2 ) z —NH 2 ,    wherein R 2 , R 3  and R 4  are independently selected from the group consisting of O and NH, u is a whole number from 3 to 10, w is a whole number from 1 to 5, x is a whole number from 2 to 5, y is a whole number from 2 to 5, and z is a whole number from 2 to 6, and wherein R 1 , R 6 , and R 7  are independently selected from the group consisting of H and (CH 2 ) v CH 3  and v is a whole number from 0 to 5, or salts thereof; and,    b) a blood product suitable for in vivo use.    
     
     
         13 . The composition of  claim 12 , wherein said blood product comprises plasma.  
     
     
         14 . The composition of  claim 13 , wherein said psoralen compound is at a concentration of between approximately 0.1 and 250 μM.  
     
     
         15 . The composition of  claim 12 , wherein said blood product comprises platelets.  
     
     
         16 . The composition of  claim 15 , further comprising a synthetic medium.  
     
     
         17 . The composition of  claim 16 , wherein said synthetic medium comprises sodium acetate.  
     
     
         18 . The composition of  claim 16 , wherein said synthetic medium comprises sodium chloride.  
     
     
         19 . The composition of  claim 16 , wherein said synthetic medium comprises sodium citrate.  
     
     
         20 . The composition of  claim 16 , wherein said synthetic medium comprises sodium phosphate.  
     
     
         21 . The composition of  claim 16 , wherein said synthetic medium comprises sodium acetate, sodium chloride, sodium citrate and sodium phosphate.  
     
     
         22 . The composition of  claim 21 , wherein said psoralen compound is at a concentration of between approximately 0.1 and 250 μM