Thrombin-free biological adhesive and use thereof as a medicament

Abstract

The invention relates to a thrombin-free, fibrinogen-based biological adhesive for therapeutic use, which comprises factor VIIa and a source of calcium ions. The invention also relates to the use of the biological adhesive as a medicament, in particular as a dressing for biological tissues, wounds or biomaterials.

What is claimed is: 
     
         1 . A thrombin-free, prothrombin-free, fibrinogen-based stable single-compound liquid biological adhesive for therapeutic use, comprising water and a mixture of fibrinogen, factor VIIa, and calcium ions. 
     
     
         2 . The biological adhesive according to  claim 1 , wherein the biological adhesive has a fibrinogen content of from about 60 mg/mL to about 120 mg/mL of the biological adhesive. 
     
     
         3 . The biological adhesive according to  claim 2 , wherein the biological adhesive has a fibrinogen content of from about 80 mg/mL to about 100 mg/mL of the biological adhesive. 
     
     
         4 . The biological adhesive according to  claim 1 , wherein the biological adhesive has a factor VIIa content of from about 50 IU/mL to about 500 IU/mL of the biological adhesive. 
     
     
         5 . The biological adhesive according to  claim 4 , wherein the biological adhesive has a factor VIIa content of from about 70 IU/mL to about 300 IU/mL of the biological adhesive. 
     
     
         6 . The biological adhesive according to  claim 5 , wherein the biological adhesive has a factor VIIa content of from about 80 IU/mL to about 120 IU/mL of the biological adhesive. 
     
     
         7 . The biological adhesive according to  claim 1 , wherein the biological adhesive has a calcium ion content of from about 4 μmols/mL to about 30 μmols/mL of the biological adhesive. 
     
     
         8 . The biological adhesive according to  claim 7 , wherein the biological adhesive has a calcium ion content of from about 8 μmols/mL to about 20 μmols/mL of the biological adhesive. 
     
     
         9 . The biological adhesive according to  claim 1 , further comprising factor XIII. 
     
     
         10 . The biological adhesive according to  claim 9 , wherein the biological adhesive has a factor XIII content of from about 100 IU/mL to about 400 IU/mL of the biological adhesive. 
     
     
         11 . The biological adhesive according to  claim 1 , wherein the biological adhesive is in a frozen form, suitable for extended storage. 
     
     
         12 . A thrombin-free, prothrombin-free, fibrinogen-based stable single-compound biological adhesive for therapeutic use, comprising water and a mixture of fibrinogen, factor VIIa, and calcium ions, wherein the biological adhesive is in a freeze-dried form that is suitable for extended storage of the biological adhesive. 
     
     
         13 . The biological adhesive according to  claim 12 , further comprising constituents of a pharmaceutically acceptable freeze-drying stabilizing formulation. 
     
     
         14 . The biological adhesive according to  claim 13 , wherein the pharmaceutically acceptable freeze-drying stabilizing formulation is a mixture comprising arginine, at least one hydrophobic amino acid and trisodium citrate. 
     
     
         15 . A kit comprising, in a package, a single container containing the thrombin-free, prothrombin-free, fibrinogen-based stable single-compound biological adhesive for therapeutic use according to  claim 1 . 
     
     
         16 . The kit according to  claim 15 , further comprising a device for dispensing the liquid adhesive. 
     
     
         17 . A method for treating damaged biological tissue, comprising applying the biological adhesive according to  claim 1  or  claim 12  to the damaged biological tissue. 
     
     
         18 . The method according to  claim 17 , wherein the damaged biological tissues are cruentous tissues or haemorrhagic wounds. 
     
     
         19 . The method according to  claim 17 , wherein the damaged biological tissues are skin or any organ capable of being surgically operated on. 
     
     
         20 . The method according to  claim 17 , wherein the biological adhesive is in a dry form, as a dressing for local application or as a gelatine capsule. 
     
     
         21 . A method for treating damaged tissues selected from the group consisting of cartilage, collagen, bone and bone powder, comprising applying plasma and the biological adhesive according to  claim 1  on the damaged tissues, and joining the damaged tissues. 
     
     
         22 . A method for merging biomaterials selected from the group consisting of alginates and polylactic acid, comprising applying plasma and the biological adhesive according to  claim 1  on the biomaterials to be merged, and joining the biomaterials.