Methods and dressings for sealing internal injuries

Abstract

Disclosed are solid and frozen haemostatic materials and dressings consisting essentially of a fibrinogen component and a fibrinogen activator. Also disclosed are methods of treating internal wounded tissue in a mammal by applying one or more of these haemostatic materials and dressings.

1 . A method for treating wounded internal tissue in a mammal comprising applying to wounded internal tissue at least one haemostatic material consisting essentially of a fibrinogen component and a fibrinogen activator for a time sufficient to join or approximate said wounded tissue and/or to reduce the flow of fluid from said wounded tissue, wherein said haemostatic material is substantially homogeneous. 
     
     
         2 . A method for treating wounded internal tissue in a mammal comprising applying to wounded internal tissue at least one haemostatic material consisting essentially of a fibrinogen component and a fibrinogen activator for a time sufficient to join or approximate said wounded tissue and/or to reduce the flow of fluid from said wounded tissue, wherein said haemostatic material is cast or formed from a single aqueous solution containing the fibrinogen component and the fibrinogen activator. 
     
     
         3 . A method for treating wounded internal tissue in a mammal comprising applying to wounded internal tissue at least one haemostatic material consisting essentially of a fibrinogen component and a fibrinogen activator for a time sufficient to join or approximate said wounded tissue and/or to reduce the flow of fluid from said wounded tissue, wherein said haemostatic material is cast or formed as a single piece. 
     
     
         4 . The method of  claim 1 ,  2  or  3 , wherein said haemostatic material includes at least one support layer. 
     
     
         5 . The method of  claim 4 , wherein said support layer comprises a backing material. 
     
     
         6 . The method of  claim 4 , wherein said support layer comprises an internal support material. 
     
     
         7 . The method of  claim 4 , wherein said support layer comprises a resorbable material. 
     
     
         8 . The method of  claim 4 , wherein said support layer comprises a non-resorbable material. 
     
     
         9 . The method of  claim 8 , wherein said non-resorbable material is selected from the group consisting of silicone polymers, paper, gauze, plastics, non-resorbable suture materials, latexes and suitable derivatives of thereof. 
     
     
         10 . The method of  claim 4 , further comprising at least one physiologically acceptable adhesive between said haemostatic material and said backing layer. 
     
     
         11 . The method of  claim 7 , wherein said resorbable material is selected from the group consisting of proteinaceous materials, carbohydrate substances and resorbable suture materials. 
     
     
         12 . The method of  claim 11 , wherein said proteinaceous material is at least one substance selected from the group consisting of keratin, silk, fibrin, collagen, gelatin and suitable derivatives thereof. 
     
     
         13 . The method of  claim 11 , wherein said carbohydrate substance is selected from the group consisting of alginic acid and salts thereof, chitin, chitosan, cellulose, n-acetyl glucosamine, proteoglycans, glycolic acid polymers, lactic acid polymers, glycolic acid/lactic acid co-polymers, suitable derivatives thereof and mixtures of two or more thereof. 
     
     
         14 . The method of  claim 1 ,  2  or  3 , wherein said haemostatic material also contains a fibrin cross-linker and/or a source of calcium ions. 
     
     
         15 . The method of  claim 1 ,  2  or  3 , wherein said haemostatic material also contains one or more of the following: at least one filler; at least one solubilizing agent; at least one foaming agent; and at least one release agent. 
     
     
         16 . The method of  claim 15 , wherein said filler is selected from the group consisting of sucrose, lactose, maltose, keratin, silk, fibrin, collagen, gelatin, albumin, polysorbate, chitin, chitosan., alginic acid and salts thereof, cellulose, proteoglycans, glycolic acid polymers, lactic acid polymers, glycolic acid/lactic acid co-polymers, and mixtures of two or more thereof. 
     
     
         17 . The method of  claim 15 , wherein said solubilizing agent is selected from the group consisting of sucrose, lactose, maltose, dextrose, mannose, trehalose, mannitol, sorbitol, albumin, sorbate, polysorbate, and mixtures of two or more thereof. 
     
     
         18 . The method of  claim 15 , wherein said release agent is selected from the group consisting of gelatin, mannitol, sorbitol, polysorbate, sorbitan, lactose, maltose, trehalose, sorbate, glucose and mixtures of two or more thereof. 
     
     
         19 . The method of  claim 15 , wherein said foaming agent is selected from the group consisting of mixtures of sodium bicarbonate/citric acid, sodium bicarbonate/acetic acid, calcium carbonate/citric acid and calcium carbonate/acetic acid. 
     
     
         20 . The method of  claim 1 ,  2  or  3 , wherein said haemostatic material also contains at least one therapeutic supplement selected from the group consisting of antibiotics, anticoagulants, steroids, cardiovascular drugs, growth factors, antibodies (poly and mono), chemoattractants, anesthetics, antiproliferatives/antitumor agents, antivirals, cytokines, colony stimulating factors, antifungals, antiparasitics, antiinflammatories, antiseptics, hormones, vitamins, glycoproteins, fibronectin, peptides, proteins, carbohydrates, proteoglycans, antiangiogenins, antigens, nucleotides, lipids, liposomes, fibrinolysis inhibitors, procoagulants, anticoagulants, vascular constrictors and gene therapy reagents. 
     
     
         21 . The method of  claim 20 , wherein said therapeutic supplement is present in an amount equal to or greater than its solubility limit in fibrin. 
     
     
         22 . The method of  claim 4 , wherein said haemostatic material further contains at least one binding agent in an amount effective to retain the physical integrity of said haemostatic material. 
     
     
         23 . The method of  claim 22 , wherein said binding agent is selected from the group consisting of sucrose, mannitol, sorbitol, gelatin, maltose, povidone, chitosan, carboxymethylcellulose and derivatives thereof. 
     
     
         24 . The method of  claim 2  or  3 , wherein said haemostatic material is substantially homogeneous throughout. 
     
     
         25 . The method of  claim 1 ,  2  or  3 , wherein said haemostatic material has been subjected to at least one process selected from the group consisting of lyophilization, drying, spray-drying, vacuum drying and vitrification, and combinations of two or more thereof. 
     
     
         26 . The method of  claim 1 ,  2  or  3 , wherein said haemostatic material has moisture content of at least 6%. 
     
     
         27 . The method of  claim 1 ,  2  or  3 , wherein said haemostatic material has moisture content of less than 6%. 
     
     
         28 . The method of  claim 1 ,  2  or  3 , wherein said haemostatic material is frozen. 
     
     
         29 . The method of  claim 1 ,  2  or  3 , wherein said fibrinogen component is a mammalian fibrinogen. 
     
     
         30 . The method of  claim 29 , wherein said mammalian fibrinogen is selected from the group consisting of bovine fibrinogen, porcine fibrinogen, ovine fibrinogen, equine fibrinogen, caprine fibrinogen, feline fibrinogen, canine fibrinogen, murine fibrinogen and human fibrinogen. 
     
     
         31 . The method of  claim 1 ,  2  or  3 , wherein said fibrinogen component is selected from the group consisting of bird fibrinogen and fish fibrinogen. 
     
     
         32 . The method of  claim 1 ,  2  or  3 , wherein said fibrinogen component is selected from the group consisting of human fibrinogen, human fibrin I, human fibrin II, human fibrinogen a chain, human fibrinogen β chain, human fibrinogen γ chain, and mixtures of two or more thereof. 
     
     
         33 . The method of  claim 29 , wherein said mammalian fibrinogen is selected from the group consisting of recombinantly produced fibrinogen and transgenic fibrinogen. 
     
     
         34 . The method of  claim 1 ,  2  or  3 , wherein said fibrinogen activator is selected from the group consisting of thrombins, prothrombins, snake venoms, and mixtures of any two or more thereof. 
     
     
         35 . The method of  claim 34 , wherein said thrombin is mammalian thrombin. 
     
     
         36 . The method of  claim 35 , wherein said mammalian thrombin is selected from the group consisting of bovine thrombin, porcine thrombin, ovine thrombin, equine thrombin, caprine thrombin, feline thrombin, canine thrombin, murine thrombin and human thrombin. 
     
     
         37 . The method of  claim 34 , wherein said thrombin is selected from the group consisting of bird thrombin and fish thrombin. 
     
     
         38 . The method of  claim 35  or  37 , wherein said thrombin is selected from the group consisting of recombinantly produced thrombin and transgenic thrombin. 
     
     
         39 . The method of  claim 1 ,  2  or  3 , wherein said method is performed as a part of a process selected from the group consisting of: vascular access sealing; hernia repair; epistaxis; and adhesion prevention. 
     
     
         40 . The method of  claim 39 , wherein said method is performed as a part of vascular access sealing and said haemostatic material is applied as a disk or pellet using a guide wire. 
     
     
         41 . A haemostatic material consisting essentially of a mixture of fibrinogen component, a fibrinogen activator and water, wherein said mixture is frozen and is stable at a temperature of less than 0° C. for at least 24 hours. 
     
     
         42 . The haemostatic material of  claim 41 , wherein said mixture also contains one or more of the following: at least one binding agent, at least one filler; at least one solubilizing agent; at least one foaming agent; and at least one release agent. 
     
     
         43 . The haemostatic material of  claim 41 , wherein said mixture also contains at least one therapeutic supplement selected from the group consisting of antibiotics, anticoagulants, steroids, cardiovascular drugs, growth factors, antibodies (poly and mono), chemoattractants, anesthetics, antiproliferatives/antitumor agents, antivirals, cytokines, colony stimulating factors, antifungals, antiparasitics, antinflammatories, antiseptics, hormones, vitamins, glycoproteins, fibronectin, peptides, proteins, carbohydrates, proteoglycans, antiangiogenins, antigens, nucleotides, lipids, liposomes, fibrinolysis inhibitors, procoagulants, anticoagulants, vascular constrictors and gene therapy reagents. 
     
     
         44 . The haemostatic material of  claim 41 , wherein said mixture also contains at least one support material.