Cross-linked gels of chemically activated carboxypolysaccharides and polyalkylene oxides

Abstract

Carboxypolysaccharides (CPS) including carboxymethyl cellulose and their derivatives are provided that can be made into sponges, gels, membranes, particulates and other forms, for a variety of antiadhesion, antithrombogenic, drug delivery and/or hemostatic applications during surgery and pharmacological therapeutics. CPSs derivatized with primary amines can be used alone or in combination with poly(ethylene glycol) and poly(ethylene oxides) and other poly(alkylene oxides) to form materials having improved drug delivery, antiadhesion, and hemostatic uses. Applications include other types of chemical modifications of CPS to provide hydrogen, ionic, Van der Walls interactions and/or covalent bonding with drugs, biologicals and other therapeutic or diagnostic purposes.

1 . A covalently cross-linked gel, comprising: 
 a derivatized carboxypolysaccharide (CPS); and    a derivatized polyalkylene oxide (PAO).    
   
   
       2 . The composition of  claim 1 , further comprising underivatized CPS.  
   
   
       3 . The composition of  claim 1 , wherein said derivatized CPS is CMC-N.  
   
   
       4 . The composition of  claim 1 , wherein said PAO is polyethylene oxide (PEO).  
   
   
       5 . The composition of  claim 1 , wherein said derivatized PAO is selected from the group consisting of methoxy-PAO-SPA, N-hydroxysuccinimide PEG, monomethoxy PEG (mPEG), di-SG-PEG and di-SE-PEG.  
   
   
       6 . The composition of  claim 1 , further comprising a drug.  
   
   
       7 . The composition of  claim 6 , wherein the drug is a hemostatic drug.  
   
   
       8 . The composition of  claim 7 , wherein said hemostatic drug is thrombin.  
   
   
       9 . The composition of  claim 6 , wherein said hemostatic drug is a vasoconstrictor.  
   
   
       10 . The composition of  claim 9 , wherein said vasoconstrictor is selected from the group consisting of norepinephrine and epinephrine.  
   
   
       11 . The composition of  claim 6 , wherein said drug is selected from the group consisting of hormones, clotting factors, antiinflammatory agents, steroids, antibiotics and vasoconstrictors.  
   
   
       12 . The composition of  claim 11 , wherein said hormone is selected from the group consisting of growth factors, peptide hormones, steroid hormones and protein hormones.  
   
   
       13 . The composition of  claim 6 , wherein said drug is a nucleic acid.  
   
   
       14 . The composition of  claim 13 , wherein said nucleic acid is a DNA.  
   
   
       15 . The composition of  claim 1 , wherein said derivatized CPS comprises a CPS and one or more members of the group consisting of primary amines, diamines, sulfonyl chlorides, tresyl chlorides, aldehydes, vinyl sulfones, carbodiimides, active esters, active aldehydes, triflurorethanesulfonyl chlorides, periodates and carbonylating agents.  
   
   
       16 . The composition of  claim 15 , wherein said carbodiimide is 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC).  
   
   
       17 . The composition of  claim 1 , wherein said composition is dried to form a membrane.  
   
   
       18 . The composition of  claim 1 , wherein said composition is a sponge.  
   
   
       19 . A cross-linked composition, comprising a CPS cross-linked with a cross-linking agent selected from the group consisting of glutaraldehyde, carbodiimides and disuccinimidyl suberate.