Biopolymer System for Tissue Sealing

Abstract

A tissue sealant for use in surgical and medical procedures for sealing the tissues of a living mammal is provided. The tissue sealant comprises a hydrogel which is formed by gelation of a premix disposed on the tissue to be sealed. The premix comprises alkylated chitosan or a gelatin, and a polybasic carboxylic acid or an oxidized polysaccharide, in an aqueous medium. The premix can also include a dehydrating reagent, a carboxyl activating reagent, or both. A specific use of the tissue sealant is in the repair of the dura mater after brain surgery to prevent leakage of cerebrospinal fluid. The tissue sealant may include a therapeutic or protective agent such as an antibiotic or an anti-inflammatory drug.

1 . A tissue sealant for sealing a biological tissue of a living mammal, the sealant comprising a hydrogel, the hydrogel being formed by gelation of a premix, the premix comprising an alkylated chitosan or a gelatin, and a polybasic carboxylic acid or an oxidized polysaccharide, in an aqueous medium. 
     
     
         2 . (canceled) 
     
     
         3 . The tissue sealant of  claim 1  wherein the hydrogel is adapted to adhere to biological tissue of a living mammal, to adhesively seal the tissue. 
     
     
         4 . The tissue sealant of  claim 1  wherein the alkylated chitosan comprises poly(oxyalkylene)chitosan, the poly(oxyalkylene)chitosan preferably comprising poly(oxyethylene)chitosan. 
     
     
         5 . The tissue sealant of  claim 1  wherein the alkylated chitosan comprises acrylated chitosan. 
     
     
         6 . The tissue sealant of  claim 1  wherein the polybasic carboxylic acid comprises an acidic polysaccharide, the acidic polysaccharide preferably comprising a hyaluronan or a carboxymethylcellulose. 
     
     
         7 .- 8 . (canceled) 
     
     
         9 . The tissue sealant of  claim 1  wherein the oxidized polysaccharide comprises oxidized dextran, oxidized starch, or oxidized hyaluronan. 
     
     
         10 .- 11 . (canceled) 
     
     
         12 . The tissue sealant of  claim 1  wherein the living mammal is a living human being. 
     
     
         13 .- 14 . (canceled) 
     
     
         15 . The tissue sealant of  claim 1  further comprising a therapeutic or protective agent. 
     
     
         16 .- 20 . (canceled) 
     
     
         21 . The tissue sealant of  claim 15  wherein the therapeutic or protective agent comprises an anti-inflammatory agent. 
     
     
         22 . The tissue sealant of  claim 15  wherein the therapeutic or protective agent comprises an anti-cancer agent. 
     
     
         23 .- 24 . (canceled) 
     
     
         25 . A medical device or formulation comprising the tissue sealant of  claim 1 . 
     
     
         26 . A method of preparing a tissue sealant of  claim 1 , for sealing a biological tissue of a living mammal, the method comprising:
 combining with mixing an alkylated chitosan or a gelatin, and a polybasic carboxylic acid or an oxidized polysaccharide, in an aqueous medium to form the premix; then,   applying the premix to biological tissue;   
       and then,
 allowing the premix to form the hydrogel by gelation such that the hydrogel formed by gelation is disposed on the biological tissue. 
 
     
     
         27 .- 29 . (canceled) 
     
     
         30 . The method of  claim 26  wherein the alkylated chitosan comprises a poly(oxyalkylene)chitosan, preferably a poly(oxyethylene)chitosan, or an acrylated chitosan. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 26  wherein the oxidized polysaccharide comprises oxidized dextran, oxidized starch, or oxidized hyaluronan. 
     
     
         33 .- 34 . (canceled) 
     
     
         35 . The method of  claim 26  further comprising dissolving the alkylated chitosan in the aqueous medium at a concentration of about 1% to about 10% by weight. 
     
     
         36 . The method of  claim 35  wherein the alkylated chitosan concentration is about 3% to about 7% by weight. 
     
     
         37 .- 45 . (canceled) 
     
     
         46 . The method of  claim 26  wherein the premix comprises a therapeutic or protective agent. 
     
     
         47 . A method of use of the tissue sealant of  claim 1  for sealing a disrupted biological tissue in need thereof in a living mammal, comprising applying the premix to the disrupted biological tissue. 
     
     
         48 .- 53 . (canceled) 
     
     
         54 . The method of  claim 47  wherein the biological tissue comprises neural tissue or dermal tissue. 
     
     
         55 . (canceled) 
     
     
         56 . The method of  claim 47  comprising adhesively sealing the disrupted biological tissue against leakage of a biological fluid. 
     
     
         57 .- 60 . (canceled)