Chitosan and polyethylene glycol copolymers and methods and devices for using same for sealing a vascular puncture

Abstract

A sealant is provided for sealing a puncture through tissue that comprises an elongate first section including a proximal end, a distal end, and a cross-section sized for delivery into a puncture through tissue, and a second section extending from the distal end of the first section. The first section may be formed from a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture. The first section comprises chitosan and at least one additional polymer. The second section may be formed from a solid mass of non-freeze-dried, non-cross-linked hydrogel precursors. The precursors are in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ crosslinking with one another to provide an adhesive layer bonded to the first section. The second section may further comprise chitosan. Apparatus and methods for delivering the sealant into a puncture through tissue are also provided.

1 - 41 . (canceled) 
     
     
         42 . A vascular sealant comprising
 a first elongated section with a proximal and distal end comprising a copolymer with
 a biodegradable polysaccharide having hemostatic and/or procoagulative properties, and a mixture of amine modified polyethylene glycol (PEG) and ester modified PEG polymers, 
 wherein the polysaccharide is covalently bound to the mixture of PEG polymers; and 
   a second section extending from the distal end of the first section comprising non-cross-linked precursors of amine modified PEG and ester modified PEG.   
     
     
         43 . The vascular sealant of  claim 42 , wherein the biodegradable polysaccharide is deacetylated chitin. 
     
     
         44 . The vascular sealant of  claim 42 , wherein the biodegradable polysaccharide is chitosan. 
     
     
         45 . The vascular sealant of  claim 42 , wherein the copolymer in the first section forms a hydrogel. 
     
     
         46 . The vascular sealant of  claim 42 , wherein amine modified PEG and ester modified PEG are present in a molar ratio of between 4:1 and 1:4. 
     
     
         47 . The vascular sealant of  claim 42 , wherein amine modified PEG and ester modified PEG are present in a ratio of equivalent active groups between a range from about 0.1 to about 5. 
     
     
         48 . The vascular sealant of  claim 42 , wherein the copolymer is freeze-dried. 
     
     
         49 . The vascular sealant of  claim 43 , wherein the chitin is at least partially deacetlyated. 
     
     
         50 . The vascular sealant of  claim 49 , wherein the chitin has a degree of deacetylation of at least 60%. 
     
     
         51 . The vascular sealant of  claim 42 , wherein the polysaccharide is chitosan having a molecular weight between about 10 kilodaltons and about 600 kilodaltons. 
     
     
         52 . The vascular sealant of  claim 43 , wherein the chitosan is selected from free chitosan, chitosan chloride, chitosan glutamate, chitosan acetate, chitosan dicarboxylic acid salts, chitosan adipate, chitosan succinate, chitosan fumarate, or combinations thereof. 
     
     
         53 . The vascular sealant of  claim 42 , wherein the first section comprises between about 0.1% and about 30% (by weight) chitosan. 
     
     
         54 . The vascular sealant of  claim 42 , wherein the second section extends from a distal end of the first section. 
     
     
         55 . The vascular sealant of  claim 42 , wherein the amine modified PEG and ester modified PEG are in equimolar amounts. 
     
     
         56 . The vascular sealant of  claim 42 , wherein the first elongated section is sized for delivery into a puncture through tissue. 
     
     
         57 . A polymer composition comprising chitosan and a mixture of amine modified PEG and ester modified PEG polymers,
 wherein the mixture comprises equimolar quantities of the amine modified PEG and the ester modified PEG polymers; and   wherein the composition forms a partially cross-linked mesh network.   
     
     
         58 . The polymer composition of  claim 57 , wherein amine modified PEG and ester modified PEG polymers are present in a ratio of equivalent active groups between a range from about 0.1 to about 5. 
     
     
         59 . The polymer composition of  claim 57 , wherein the chitosan has a molecular weight between about 10 kilodaltons and about 600 kilodaltons. 
     
     
         60 . The polymer composition of  claim 57 , wherein the chitosan is selected from free chitosan, chitosan chloride, chitosan glutamate, chitosan acetate, chitosan dicarboxylic acid salts, chitosan adipate, chitosan succinate, chitosan fumarate, or combinations thereof. 
     
     
         61 . A method for producing a two section porous polymer sealant comprising
 producing a first section by
 combining chitosan with an equimolar mixture of amine modified PEG and ester modified PEG polymers to form a hydrogel, 
 wherein chitosan and the amine modified PEG and ester modified PEG polymers are covalently bound and form a porous hydrogel material; and 
 freeze drying the hydrogel; and 
   producing a second section by
 applying non-cross-linked precursors of the amine modified PEG and the ester modified PEG polymers to an end of the first section.