Methods of using therapeutic fibrinogen compositions

Abstract

A therapeutic composition effective on contact with thrombin at a site of treatment in a patient as a tissue adhesive, hemostat or sealant, said composition comprising non-autologous, non-single donor mammalian fibrinogen that is capable of polymerizing when provided in solution at said site at a concentration of about 30 mg/ml thereof or less, to a fibrin network having therapeutically effective strength, wherein said composition contains less than about 30% (w/w), based on total protein mass present therein, of proteins other than fibrinogen, and further comprises a sufficient amount of one or more low molecular weight physiologically-compatible solutes such that said composition, if formulated as a lyophilized material, can be reconstituted therefrom at room temperature in sterile water for injection in about 30 minutes or less, at about 25 mg/ml of said fibrinogen. Additionally, methods for producing and maintaining said composition, and methods for the use thereof.

1 - 17 . (canceled)  
     
     
         18 . A method for inducing tissue adhesion, sealing of tissue, or hemostatis in a mammalian patient at a site of treatment therein comprising contacting said site with a therapeutically effective amount of a therapeutic composition effective on contact with thrombin at a site of treatment in a patient as a tissue adhesive, hemostat or sealant, said composition comprising non-autologous, non-single donor mammalian, clottable fibrinogen recovered from a process comprising precipitating fibrinogen from a sample of non-human, mammalian blood plasma with polyethylene glycol 1000 and reprecipitating said fibrinogen with glycine, wherein precipitation of said fibrinogen with polyethylene glycol is performed only once, such that at least about 90% of the fibrinogen present in said sample is recovered, wherein said recovered fibrinogen polymerizes when provided in solution at said site at a therapeutically effective fibrinogen concentration of about 30 mg/ml thereof or less, to a fibrin network having therapeutically effective strength, wherein said therapeutically effective fibrinogen concentration at said site is about 30 mg/ml or less, 
 wherein said composition contains less than about 30% (w/w), based on total protein mass present therein, of proteins other than fibrinogen, and said composition further comprises a sufficient amount of one or more low molecular weight physiologically-compatible solutes such that said composition, if formulated as a lyophilized material, can be reconstituted therefrom at room temperature in sterile water for injection in about 30 minutes or less, at about 25 mg/ml of said fibrinogen.    
     
     
         19 . A method according to  claim 18  further comprising contacting said site or said composition with an amount of thrombin effective to convert fibrinogen of said composition to a fibrin network having therapeutically effective strength.  
     
     
         20 . A method according to  claim 19  wherein the amount of thrombin utilized therein is from about 0.1 NIH unit up to about 1000 NIH units thereof per milliliter of fibrinogen-containing therapeutic composition utilized therein.  
     
     
         21 . A method according to  claim 20  wherein said amount of thrombin is from about 1.0 NIH unit up to about 300 NIH units thereof.  
     
     
         22 . A method according to  claim 19  wherein said thrombin and said fibrinogen-containing therapeutic composition are applied separately to said site of treatment.  
     
     
         23 . A method according to  claim 19  wherein said thrombin and said fibrinogen-containing therapeutic composition are applied concurrently to said site of treatment.  
     
     
         24 . A method according to  claim 18  wherein said thrombin and said fibrinogen-containing therapeutic composition are first combined and then applied to said site of treatment.  
     
     
         25 . A method according to  claim 18  wherein said fibrinogen-containing therapeutic composition that contacts said site of treatment is in the form of a dry lyophilized powder.  
     
     
         26 . A method for inducing tissue adhesion, sealing of tissue, or hemostatis in a mammalian patient at a site of treatment therein comprising contacting said site with a therapeutically effective amount of a therapeutic composition comprising, as percent by weight of total protein contained therein, 
 clottable fibrinogen, at about 56% or greater;    serum albumin, at less than about 20%;    gamma globulin, at less than about 10%;    plasminogen, at less than about 1%; and    plasma fibronectin, at less than about 3%.