Solid dressing for treating wounded tissue

Abstract

Disclosed are solid dressings for treated wounded tissue in mammalian patients, such as a human, comprising a haemostatic layer consisting essentially of a fibrinogen component and a fibrinogen activator, wherein the haemostatic layer(s) is cast or formed from a single aqueous solution containing the fibrinogen component and the fibrinogen activator. Also disclosed are methods for treating wounded tissue using these dressings and frozen compositions useful for preparing the haemostatic layer(s) of these dressings.

1 . A solid dressing for treating wounded tissue in a mammal comprising at least one haemostatic layer consisting essentially of a fibrinogen component and a fibrinogen activator, wherein said haemostatic layer is formed from a single aqueous solution containing said fibrinogen component and said fibrinogen activator. 
     
     
         2 . A solid dressing for treating wounded tissue in a mammal comprising at least one haemostatic layer consisting essentially of a fibrinogen component and a fibrinogen activator, wherein said haemostatic layer is cast as a single piece. 
     
     
         3 . The solid dressing of  claim 1  or  2 , further comprising at least one support layer. 
     
     
         4 . The solid dressing of  claim 3 , wherein said support layer comprises a backing material. 
     
     
         5 . The solid dressing of  claim 3 , wherein said support layer comprises an internal support material. 
     
     
         6 . The solid dressing of  claim 3 , wherein said support layer comprises a resorbable material 
     
     
         7 . The solid dressing of  claim 3 , wherein said support layer comprises a non-resorbable material. 
     
     
         8 . The solid dressing of  claim 7 , wherein said non-resorbable material is selected from the group consisting of silcone polymers, paper, gauze and latexes. 
     
     
         9 . The solid dressing of  claim 3 , further comprising at least physiologically acceptable adhesive between said haemostatic layer and said backing layer. 
     
     
         10 . The solid dressing of  claim 6 , wherein said resorbable material is selected from the group consisting of proteinaceous materials and carbohydrate substances. 
     
     
         11 . The solid dressing of  claim 10 , wherein said proteinaceous material is at least one substance selected from the group consisting of keratin, silk, fibrin, collagen and gelatin. 
     
     
         12 . The solid dressing of  claim 10 , 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 and mixtures of two or more thereof. 
     
     
         13 . The solid dressing of  claim 1  or  2 , wherein said haemostatic layer also contains a fibrin cross-linker and/or a source of calcium ions. 
     
     
         14 . The solid dressing of  claim 1  or  2 , wherein said haemostatic layer 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. 
     
     
         15 . The solid dressing of  claim 14 , 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. 
     
     
         16 . The solid dressing of  claim 14 , 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. 
     
     
         17 . The solid dressing of  claim 14 , 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. 
     
     
         18 . The solid dressing of  claim 14 , 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. 
     
     
         19 . The solid dressing of  claim 1  or  2 , wherein said haemostatic layer 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 and gene therapy reagents. 
     
     
         20 . The solid dressing of  claim 19 , wherein said therapeutic supplement is present in an amount equal to or greater than its solubility limit in fibrin. 
     
     
         21 . The solid dressing of  claim 3 , wherein said haemostatic layer further contains at least one binding agent in an amount effective to improve the adherence of said haemostatic layer to said support layer. 
     
     
         22 . The solid dressing of  claim 21 , wherein said binding agent is selected from the group consisting of sucrose, mannitol, sorbitol, gelatin, maltose, povidone, chitosan and carboxymethylcellulose. 
     
     
         23 . The solid dressing of  claim 1  or  2 , wherein said haemostatic layer is substantially homogeneous throughout. 
     
     
         24 . The solid dressing of  claim 1  or  2 , wherein said haemostatic layer is a monolith. 
     
     
         25 . The solid dressing of  claim 1  or  2 , wherein said haemostatic layer has been lyophilized. 
     
     
         26 . The solid dressing of  claim 1  or  2 , wherein said haemostatic layer has moisture content of at least 6%. 
     
     
         27 . The solid dressing of  claim 1  or  2 , wherein said haemostatic layer has moisture content of less than 6%. 
     
     
         28 . The solid dressing of  claim 1  or  2 , wherein said fibrinogen component is a mammalian fibrinogen. 
     
     
         29 . The solid dressing of  claim 28 , 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. 
     
     
         30 . The solid dressing of  claim 1  or  2 , wherein said fibrinogen component is selected from the group consisting of bird fibrinogen and fish fibrinogen. 
     
     
         31 . The solid dressing of  claim 1  or  2 , 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. 
     
     
         32 . The solid dressing of  claim 28 ,  30  or  31 , wherein said fibrinogen is selected from the group consisting of recombinantly produced fibrinogen and transgenic fibrinogen. 
     
     
         33 . The solid dressing of  claim 28 , wherein said mammalian fibrinogen is present in an amount between 1.5 mg/cm 2  of the wound-facing surface of said dressing and 13.0 mg/cm 2  of the wound-facing surface of said dressing. 
     
     
         34 . The solid dressing of  claim 1  or  2 , 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 solid dressing of  claim 34 , wherein said thrombin is mammalian thrombin. 
     
     
         36 . The solid dressing 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 solid dressing of  claim 34 , wherein said thrombin is selected from the group consisting of bird thrombin and fish thrombin. 
     
     
         38 . The solid dressing of  claim 35  or  37 , wherein said thrombin is selected from the group consisting of recombinantly produced thrombin and transgenic thrombin. 
     
     
         39 . The solid dressing of  claim 34 , wherein said thrombin is present in an amount between 2.50 Units/mg of said fibrinogen component and 0.025 Units/mg of said fibrinogen component. 
     
     
         40 . A method of treating wounded tissue in a mammal, comprising placing a solid dressing of  claim 1  or  2  to said wounded tissue and applying sufficient pressure to said dressing for a sufficient time for enough fibrin to form to reduce the loss of blood and/or other fluid from said wounded tissue. 
     
     
         41 . A composition of matter 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 composition 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 composition 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 and gene therapy reagents.