Novel Heparin Entities and Methods of Use

Abstract

The present invention relates to immobilized biologically active entities that retain a significant biological activity following manipulation. The invention also comprises a medical substrate comprising a heparin entity bound onto a substrate via at least one heparin molecule, wherein said bound heparin entity is heparinase-1 sensitive.

1 . A heparin entity comprising:
 at least one heparin molecule and at least one core molecule such that when said heparin entity is bound onto a substrate via said at least one heparin molecule, said heparin entity is heparinase sensitive.   
     
     
         2 . The heparin entity of  claim 1 , wherein said substrate is selected from the group consisting of polyethylene, polyurethane, silicone, polyamide-containing polymers, polypropylene, polytetrafluoroethylene, expanded-polytetrafluoroethylene and biocompatible metals. 
     
     
         3 . The heparin entity of  claim 1 , wherein said substrate is expanded-polytetrafluoroethylene. 
     
     
         4 . The heparin entity of  claim 2 , wherein said biocompatible metal is Nitinol. 
     
     
         5 . The heparin entity of  claim 1 , wherein said substrate is a component of a medical device. 
     
     
         6 . The heparin entity of  claim 5 , wherein said medical device is selected from the group consisting of grafts, vascular grafts, stents, stent-grafts, bifurcated grafts, bifurcated stents, bifurcated stent-grafts, patches, plugs, drug delivery devices, catheters, cardiac leads, balloons and indwelling filters. 
     
     
         7 . The heparin entity of  claim 6 , wherein said stents can be used in cardiac, peripheral or neurological applications. 
     
     
         8 . The heparin entity of  claim 6 , wherein said stent-grafts can be used in cardiac, peripheral or neurological applications. 
     
     
         9 . The heparin entity of  claim 1 , wherein said core molecule is either cyclic, linear, branched, dendritic, T, Y or star shaped. 
     
     
         10 . The heparin entity of  claim 1 , wherein said core molecule is selected from the group consisting of proteins, polypeptides, hydrocarbons, polysaccharides, aminoglycosides, and polymers. 
     
     
         11 . The heparin entity of  claim 10 , wherein said protein is selected from the group consisting of albumin, colistin and polylysine. 
     
     
         12 . The heparin entity of  claim 10 , wherein said polysaccharide is selected from the group consisting of cyclodextrin, cellulose, and chitosan. 
     
     
         13 . The heparin entity of  claim 10 , wherein said polymer is selected from the group consisting of polyethylene glycol (PEG) and co-polymers of tetrafluoroethylene. 
     
     
         14 . The heparin entity of  claim 1 , wherein said heparin is derived from bovine or porcine sources. 
     
     
         15 . The heparin entity of  claim 1 , wherein after heparinase treatment heparin or fragments thereof will not be detected on said substrate. 
     
     
         16 . The medical substrate of  claim 1 , wherein after heparinase treatment heparin or fragments thereof will be detect at a significantly lower level than before heparinase treatment. 
     
     
         17 . The heparin entity of  claim 15 , wherein heparin or fragments thereof is detected by a label that binds to heparin or fragments thereof. 
     
     
         18 . The heparin entity of  claim 17 , wherein said label that binds to heparin or fragments thereof is selected from the group consisting of dyes, antibodies, and proteins. 
     
     
         19 . The heparin entity of  claim 18 , wherein said dye is toluidine blue. 
     
     
         20 . The heparin entity of  claim 1 , wherein after heparinase treatment an insignificant amount of toluidine blue will bind to residual heparin or fragments thereof but will not be visually detected on said substrate. 
     
     
         21 . The heparin entity of  claim 1 , wherein after heparinase treatment an insignificant amount of toluidine blue will bind to residual heparin or fragments thereof, and wherein detector readings will be about background levels or be insignificantly different from background levels when compared to a substrate without heparin entities. 
     
     
         22 . The heparin entity of  claim 1 , wherein said heparin entity is bound onto a substrate via at least one heparin molecule and wherein said bound heparin molecule is attached to said substrate via end point attachment. 
     
     
         23 . The heparin entity of  claim 1 , wherein said heparin entity is bound onto a substrate via at least one heparin molecule and wherein said bound heparin molecule is attached to said substrate via loop attachment. 
     
     
         24 . The heparin entity of  claim 1 , wherein said heparin entity is bound onto a substrate via at least one heparin molecule and wherein said bound heparin molecule is attached to said substrate via end point aldehyde. 
     
     
         25 . The heparin entity of  claim 1 , wherein said heparin entity is bound onto a substrate via at least one heparin molecule and wherein said bound heparin molecule is attached to said substrate via aldehydes along the length said heparin. 
     
     
         26 . An ATIII binding entity comprising;
 a core molecule,   a polysaccharide chain attached to the core molecule, and   a free terminal aldehyde moiety on the polysaccharide chain.   
     
     
         27 . The ATIII binding entity of  claim 26 , wherein said polysaccharide chain is heparin. 
     
     
         28 . The ATIII binding entity of  claim 26 , wherein said core molecule is selected from the group consisting of a protein, a hydrocarbon, an aminoglycoside, a polysaccharide and a polymer. 
     
     
         29 . The ATIII binding entity of  claim 28 , wherein said protein is selected from the group consisting of albumin, colistin, and polylysine. 
     
     
         30 . The ATIII binding entity of  claim 28 , wherein said polysaccharide is selected from the group consisting of cyclodextrin, cellulose, and chitosan. 
     
     
         31 . The ATIII binding entity of  claim 28 , wherein said polymer is selected from the group consisting of polyethylene glycol (PEG) and co-polymers of tetrafluoroethylene. 
     
     
         32 . The ATIII binding entity of  claim 27 , wherein said heparin is derived from bovine or porcine sources. 
     
     
         33 . The ATIII binding entity of  claim 27 , wherein said heparin is bound onto the core molecule via end point attachment. 
     
     
         34 . The ATIII binding entity of  claim 27 , wherein said heparin is bound onto a substrate via end point attachment. 
     
     
         35 . The ATIII binding entity of  claim 34 , wherein said substrate is selected from the group consisting of polyethylene, polyurethane, silicone, polyamide-containing polymers, and polypropylene, polytetrafluoroethylene, expanded-polytetrafluoroethylene and biocompatible metals. 
     
     
         36 . The ATIII binding entity of  claim 35 , wherein said substrate is expanded-polytetrafluoroethylene. 
     
     
         37 . The ATIII binding entity of  claim 35 , wherein said biocompatible metal is Nitinol. 
     
     
         38 . The ATIII binding entity of  claim 34 , wherein said substrate is a component of a medical device. 
     
     
         39 . The heparin entity of  claim 38 , wherein said medical device is selected from the group consisting of grafts, vascular grafts, stents, stent-grafts, bifurcated grafts, bifurcated stents, bifurcated stent-grafts, patches, plugs, drug delivery devices, catheters and cardiac leads. 
     
     
         40 . The heparin entity of  claim 39 , wherein said stents can be used in cardiac, peripheral or neurological applications.