Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers

Abstract

A biocompatible and biodegradable barrier material is applied to a tissue region, e.g., to seal a vascular puncture site. The barrier material comprises a compound, which is chemically cross-linked without use of an enzyme to form a non-liquid mechanical matrix. The compound preferably includes a protein comprising recombinant or natural serum albumin, which is mixed with a polymer that comprises poly(ethylene) glycol (PEG), and, most preferably, a multi-armed PEG polymer.

We claim:  
     
         1 . A method for creating a biocompatible and biodegradable barrier to seal a vascular puncture site comprising the steps of 
 providing a first liquid component,    providing a second liquid component, the first and second liquid components being free of an enzyme, and    mixing the first and second liquid components by dispensing the components into a catheter tube deployed at the vascular puncture site, wherein, upon mixing, the first and second liquid components chemically cross-link to form a mechanical non-liquid matrix sealing the vascular puncture site.    
     
     
         2 . A method for creating a biocompatible barrier comprising the steps of mixing a protein solution and a polymer solution including a derivative of a hydrophilic polymer with a functionality of at least three, wherein, upon mixing, the protein solution and the polymer solution cross-link to form a mechanical non-liquid matrix.  
     
     
         3 . A method for creating a biocompatible barrier comprising the steps of 
 providing a protein solution,    providing a polymer solution including a derivative of a hydrophilic polymer with a functionality of at least three, and    mixing the protein and polymer solutions by dispensing the protein solution and the polymer solution into a channel, wherein, upon mixing, the protein solution and the polymer solution cross-link to form a mechanical non-liquid matrix.    
     
     
         4 . A method for creating a biocompatible barrier to seal a vascular puncture site comprising the steps of 
 providing a protein solution,    providing a polymer solution including a derivative of a hydrophilic polymer with a functionality of at least three, and    mixing the protein and polymer solutions by dispensing the protein solution and the polymer solution into a catheter tube deployed at a vascular puncture site, wherein, upon mixing, the protein solution and the polymer solution cross-link to form a mechanical non-liquid matrix sealing the puncture site.    
     
     
         5 . A method according to  claim 2  or  3  or  4 , wherein the protein solution comprises recombinant or natural human serum albumin.  
     
     
         6 . A method according to  claim 5 , wherein the human serum albumin is at a concentration of about 25% or less.  
     
     
         7 . A method according to  claim 2  or  3  or  4 , wherein the polymer is comprised of poly(ethylene glycol)(PEG).  
     
     
         8 . A method according to  claim 7 , wherein the PEG comprises a multi-armed polymer structure.  
     
     
         9 . A method according to  claim 2  or  3  or  4 , wherein the polymer comprises a compound of the formula PEG-(DCR-CG)n, where PEG is poly(ethylene glycol), DCR is a degradation control region, CG is a cross-linking group, and n is equal to or greater than three.  
     
     
         10 . A method according to  claim 9 , wherein the compound comprises a multi-armed polymer structure.  
     
     
         11 . A method according to  claim 9 , wherein the compound comprises poly(ethylene glycol) tetra-succinimidyl glutarate.  
     
     
         12 . A method according to  claim 9 , wherein the compound comprises poly(ethylene glycol)tetra-succinimidyl succinate.