Radiographic contrasting agents and radio-opaque polymeric materials for medical devices

Abstract

The present invention discloses a radiographic contrasting agent containing multiple aromatic groups, each of which is substituted with at least three halogen atoms. The radiographic contrasting agent can initiate a polymerization process. The present invention also discloses a radio-opaque polymeric material that comprises a biodegradable polymer having at least one radiographic contrasting moiety covalently attached thereto. The radio-opaque polymeric material provides enhanced contrasting intensity in radiographic imaging. The radio-opaque polymeric material can be applied on at least a portion of one surface of a medical device. The radio-opaque polymeric material can also be used to construct a medical device, a component thereof, or a portion of a component thereof.

1 . A radiographic contrasting agent comprising a monosaccharide backbone or an aliphatic or alicyclic backbone of 2 to 12 carbon atoms, a reactive nucleophilic group, and at least two halogen-substituted aromatic groups, wherein each of the at least two halogen-substituted aromatic groups is substituted with at least three halogen atoms and is covalently attached to the monosaccharide backbone or the aliphatic or alicyclic backbone through a linkage group, wherein the linkage group is oxygen, sulfur, —NH—, 
 —O(CO)—, —(CO)O—, —NH(CO)—, —(CO)NH—, —O(SO 2 )—, —(SO 2 )O—, —O(SO)—, —(So)O—,    —NH(SO 2 )—, —(SO 2 )NH—, —NH(SO)—, —(SO)NH—, or triazole.    
   
   
       2 . The radiographic contrasting agent of  claim 1 , having the following structure:  
     
       
         
         
             
             
         
       
       wherein R is a hydrogen atom, or an alkyl group having 1 to 4 carbon atoms;  
       X is oxygen, sulfur, —NH, —O(CO)—, —(CO)O—, —NH(CO)—, —(CO)NH—, —O(SO 2 )—,  
       —(SO 2 )O—, —O(SO)—, —(SO)O—, —NH(SO 2 )—, —(SO 2 )NH—, —NH(SO)—, —(SO)NH—, or triazole; Y is an aromatic group substituted with at least three halogen atoms; n and m are the same or different, and are independently zero or an integer of 1 to 4.  
     
   
   
       3 . The radiographic contrasting agent of  claim 2 , wherein R is a hydrogen atom.  
   
   
       4 . The radiographic contrasting agent of  claim 3 , wherein X is —O(CO)—, —NH(CO)—, or triazole.  
   
   
       5 . The radiographic contrasting agent of  claim 4 , wherein n and m are both zero.  
   
   
       6 . The radiographic contrasting agent of  claim 1 , wherein the at least three halogen atoms are bromine, iodine, or combinations thereof.  
   
   
       7 . The radiographic contrasting agent of  claim 1 , having the following structure:  
     
       
         
         
             
             
         
       
     
   
   
       8 . The radiographic contrasting agent of  claim 1 , having one of the following structures:  
     
       
         
         
             
             
         
       
     
   
   
       8 . A radio-opaque polymeric material comprising a biodegradable polymer having at least one radiographic contrasting moiety covalently attached thereto, wherein the at least one radiographic contrasting moiety is covalently attached to the biodegradable polymer through a functional group derived from a nucleophilic reaction, and the at least one radiographic contrasting moiety comprises a monosaccharide backbone or an aliphatic or alicyclic backbone of 2-12 carbon atoms, and at least two halogen-substituted aromatic groups, wherein each of the at least two halogen-substituted aromatic groups is substituted with at least three halogen atoms and is covalently attached to the monosaccharide backbone or the aliphatic or alicyclic backbone through a linkage group, wherein the linkage group is oxygen, sulfur, —NH—, —O(CO)—, —(CO)O—, —NH(CO)—, 
 —(CO)NH—, —O(SO 2 )—, —(SO 2 )O—, —O(SO)—, —(SO)O—, —NH(SO 2 )—, —(SO 2 )NH—,    —NH(SO)—, —(SO)NH—, or triazole.    
   
   
       9 . The radio-opaque polymeric material of  claim 8 , wherein the at least one radiographic contrasting moiety has the following structure:  
     
       
         
         
             
             
         
       
       wherein R is a hydrogen atom, or an alkyl group having 1 to 4 carbon atoms;  
       X is oxygen, sulfur, —NH, —O(CO)—, —(CO)O—, —NH(CO)—, —(CO)NH—, —O(SO 2 )—,  
       —(SO 2 )O—, —O(SO)—, —(SO)—, —NH(SO 2 )—, —(SO 2 )NH—, —NH(SO)—, or —(SO)NH—; Y is an aromatic group substituted with at least three halogen atoms; n and m are the same or different, and are independently zero or an integer of 1 to 4.  
     
   
   
       10 . The radio-opaque polymeric material of  claim 9 , wherein R is a hydrogen atom; and X is —O(CO)—, —NH(CO)—, or triazole.  
   
   
       11 . The radio-opaque polymeric material of  claim 10 , wherein n and m are both zero.  
   
   
       12 . The radio-opaque polymeric material of  claim 9 , wherein the at least three halogen atoms are bromine, iodine, or combinations thereof.  
   
   
       13 . The radio-opaque polymeric material of  claim 9 , wherein the biodegradable polymer having at least one radiographic contrasting moiety covalently attached thereto comprises monomer units selected from the group consisting of glycolide, lactide, dioxane, caprolactone, trimethylene carbonate, hydroxybutyrate, and combinations thereof.  
   
   
       14 . A medical device, wherein at least one portion of the medical device is radio-opaque, the at least one radio-opaque portion of the medical device comprising a radio-opaque polymeric material, which comprises a biodegradable polymer having at least one radiographic contrasting moiety covalently attached thereto, wherein the at least one radiographic contrasting moiety is covalently attached to the biodegradable polymer through a functional group derived from a nucleophilic reaction, and the at least one radiographic contrasting moiety comprises a monosaccharide backbone or an aliphatic or alicyclic backbone of 2 to 12 carbon atoms, and at least two halogen-substituted aromatic groups, wherein each of the at least two halogen-substituted aromatic groups is substituted with at least three halogen atoms and is covalently attached to the monosaccharide backbone or the aliphatic or alicyclic backbone through a linkage group, wherein the linkage group is oxygen, sulfur, —NH—, —O(CO)—, —(CO)O—, —NH(CO)—, 
 —(CO)NH—, —O(SO 2 )—, —(SO 2 )O—, —O(SO)—, —(SO)O—, —NH(SO 2 )—, —(SO 2 )NH—,    —NH(SO)—, —(SO)NH—, or triazole.    
   
   
       15 . The medical device of  claim 14 , wherein the at least one radiographic contrasting moiety has the following structure:  
     
       
         
         
             
             
         
       
       wherein R is a hydrogen atom, or an alkyl group having 1 to 4 carbon atoms;  
       X is oxygen, sulfur, —NH, —O(CO)—, —(CO)O—, —NH(CO)—, —(CO)NH—, —O(SO 2 )—,  
       —(SO 2 )O—, —O(SO)—, —(SO)O—, —NH(SO 2 )—, —(SO 2 )NH—, —NH(SO)—, —(SO)NH—, or triazole; Y is an aromatic group substituted with at least three halogen atoms; n and m are the same or different, and are independently zero or an integer of 1 to 4.  
     
   
   
       16 . The medical device of  claim 15 , wherein R is a hydrogen atom; and X is 
 —O(CO)—, —NH(CO)—, or triazole.    
   
   
       17 . The medical device of  claim 16 , wherein n and m are both zero.  
   
   
       18 . The medical device of  claim 15 , wherein the at least three halogen atoms are bromine, iodine, or combinations thereof.  
   
   
       19 . The medical device of  claim 15 , wherein the biodegradable polymer having at least one radiographic contrasting moiety covalently attached thereto comprises monomer units selected from the group consisting of glycolide, lactide, dioxane, caprolactone, trimethylene carbonate, hydroxybutyrate, and combinations thereof.  
   
   
       20 . The medical device of  claim 15 , wherein the radio-opaque portion of the medical device is at least a portion of one surface of the medical device, a component of the medical device, or a portion of a component of the medical device.  
   
   
       21 . The medical device of  claim 15  is implantable.