Monomeric compositions effective as wound closure devices

Abstract

A biocompatible monomer composition includes: (A) at least one monomer, which forms a medically acceptable polymer; (B) at least one plasticizing agent present in the composition in an amount of from 0.5 wt. to 15 wt. % of the composition; and (C) at least one acidic stabilizing agent having a pK a ionization constant of from about 1 to about 7. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g., body tissues, includes (a) holding damaged tissue edges together to form abutted tissue surfaces; (b) applying to the abutted tissue surfaces an excessive amount of a composition containing 1) at least one monomer, which forms a medically acceptable biodegradable polymer, 2) at least one plasticizing agent; and 3) at least one acidic stabilizing agent; and (c) maintaining the surfaces in contact until the composition polymerizes to form a thick film of polymerized composition bridging the abutted tissue surfaces.

What is claimed is:  
     
         1 . A method of joining together living tissue surfaces of an incision or a laceration, comprising: 
 (a) holding together at least two tissue surfaces of an incision or laceration to form abutted tissue surfaces;    (b) applying across said abutted tissue surfaces an amount of an adhesive composition comprising at least one α-cyanoacrylate monomer, which forms a medically acceptable polymer; and    (c) maintaining said tissue surfaces in contact until said composition polymerizes to form a film of polymerized composition on said abutted tissue surface,    said film having a thickness of at least 0.1 mm and said film having a higher film strength than a film of lesser thickness,    wherein said applying is by an applicator having an applicator tip.    
     
     
         2 . A method according to  claim 1 , wherein said applicator tip comprises a polymerization or cross-linking initiator or accelerator for said adhesive composition.  
     
     
         3 . A method according to  claim 2 , wherein said initiator or accelerator is selected from the group consisting of detergents, surfactants, emulsifiers, amines, imines, amides, phosphines, phosphates, phosphonium salts, alcohols, inorganic bases, thiourea, polysulfides, polymeric cyclic esters, carbonates, organometallic compounds, and phase transfer catalysts.  
     
     
         4 . A method according to  claim 3 , wherein said surfactants are selected from the group consisting of polysorbate 80, poloxamers, benzalkonium chloride, tetrabutylammonium bromide, sodium tetradecyl sulfate, and dodecyldimethyl (3-sulfopropyl) ammonium hydroxide.  
     
     
         5 . A method according to  claim 1 , wherein said applicator tip is integral with said applicator.  
     
     
         6 . A method according to  claim 1 , wherein said applicator is a syringe, a flexible cylinder, a tube, a pipette, or an eyedropper.  
     
     
         7 . A method according to  claim 2 , wherein said α-cyanoacrylate monomer is selected from the group consisting of 2-octyl cyanoacrylate, dodecyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, butyl cyanoacrylate, methyl cyanoacrylate, 3-methoxybutyl cyanoacrylate, 2-butoxyethyl cyanoacrylate, 2-isopropoxyethyl cyanoacrylate, and 1-methoxy-2-propyl cyanoacrylate.  
     
     
         8 . A method according to  claim 1 , wherein said composition is sterile.  
     
     
         9 . A method according to  claim 1 , wherein said film has a thickness of at least 0.2 mm.  
     
     
         10 . A method according to  claim 1 , wherein said adhesive composition comprises at least one plasticizing agent present in the composition in an amount of from 0.5 wt. % to 16 wt. % of the composition; and at least one acidic stabilizing agent having a pK a  ionization constant of from about 0 to about 7.  
     
     
         11 . A method according to  claim 1 , wherein said composition further comprises at least one plasticizing agent in an amount ranging from 3 wt. % to 9 wt. % of said composition and at least one acidic stabilizing agent having a pK a  of from about 1 to about 5.  
     
     
         12 . A method according to  claim 11 , wherein said plasticizing agent is present in an amount ranging from 4 wt. % to 7 wt. % of said composition.  
     
     
         13 . A method according to  claim 11 , wherein said composition is sterile.  
     
     
         14 . A method according to  claim 1 , wherein more than one application of said adhesive composition is provided across said abutted tissue surfaces.  
     
     
         15 . A method according to  claim 14 , wherein said adhesive composition applied across said abutted tissue surfaces is allowed to at least partially polymerize prior to subsequent coatings or applications of said adhesive composition.  
     
     
         16 . A method according to  claim 1 , wherein said adhesive composition polymerizes to form a bridge across said abutted tissue surfaces.  
     
     
         17 . A method according to  claim 1 , wherein said film has a thickness of 0.2 mm to 3.0 mm.  
     
     
         18 . A film formed across abutted tissue surfaces made by the method of  claim 1.