Drug target for preventing and treating periodontal disease, improving healing of periodontal wounds and promoting oral health

Abstract

The present invention relates to the use of a component of the plasminogen-activating pathway and use of compounds which have the capacity to activate plasminogen directly or via the plasminogen-activating pathway, for prophylaxis, prevention and treatment of periodontal disease including peri-implantitis, healing of periodontal wounds and prompting oral health in human and non-human subjects.

What is claimed is: 
     
         1 : Use of a compound that is a component of the plasminogen-activating pathway or has the capacity to activate plasminogen or directly via the plasminogen-activating pathway for the manufacture of a pharmaceutical composition comprising an effective amount of the compound for the prophylaxis, prevention and/or treatment of infectious periodontal disease in a subject in need of such treatment. 
     
     
         2 : Use according to  claim 1 , wherein the component of the plasminogen-activating pathway is selected from plasminogen, Lys-plasminogen, Glu-plasminogen, plasmin, kringle domains of plasminogen and plasmin, mini-plasminogen, mini-plasmin, plasminogen activators, tPA, and uPA or wherein the compound with the capacity to activate plasminogen directly or via the plasminogen-activating pathway is selected from streptokinase, saruplase, alteplase, reteplase, tenecteplase, anistreplase, monteplase, lanoteplase, pamiteplase, staphylokinase and recombinant forms and variants of the components of the plasminogen-activating pathway 
     
     
         3 : Use according to  claim 1 , wherein the subject is a human, and the component of the plasminogen-activating pathway human plasminogen. 
     
     
         4 : Use according to  claim 1 , wherein the subject is a human, and the component of the plasminogen-activating pathway is human plasmin. 
     
     
         5 : Use according to  claim 1 , wherein the subject is a non-human mammal. 
     
     
         6 : Use according to  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         7 : Use according to  claim 1 , wherein composition is selected from the group consisting of an aqueous solution, a gargling solution, a gel, a lotion, a balm, a powder, a paste, a toothpaste, a bandage, or a wound dressing. 
     
     
         8 : Use according to  claim 1 , wherein the composition is administered by a spray. 
     
     
         9 : Use according to  claim 1 , wherein the administering is selected from topical, oral, local and systemic administration. 
     
     
         10 : Use according to  claim 9 , wherein the administering is topical administrator. 
     
     
         11 . Use according to  claim 10 , wherein the composition comprises from about 1 μg to about 500 μg plasminogen per square centimeter of the application area. 
     
     
         12 : Use according to  claim 1 , wherein the periodontal disease is, or is caused by, a bacterial infection. 
     
     
         13 : Use according to  claim 1 , which further activates inflammatory cells, enhances keratinocyte migration, reduces bacterial growth, removes necrotic tissue, improves tissue remodelling and/or enhances cytokine expression. 
     
     
         14 : Use according to  claim 1 , wherein the administering is repeated at least once. 
     
     
         15 : Use according to  claim 13 , wherein the administering is repeated daily. 
     
     
         16 : Use according to according to any of  claims 1  to  15 , wherein periodontal disease is selected from, periodontitis, gingivitis, necrotizing gingivitis, periimplantitis, and peri-implant mucositis, 
     
     
         17 : Use of a compound that a component of the plasminogen-activating pathway or a compound which has the capacity to activate plasminogen directly or via the plasminogen-activating pathway for the manufacture of a pharmaceutical composition comprising an effective amount of such compound for promoting the healing of infectious periodontal wounds in a subject in need of such treatment 
     
     
         18 : Use according to  claim 17 , which further reduces fibrin deposition, promotes keratinocyte migration, enhances cytokine expressions, removes necrotic tissue, activates inflammatory cells and/or improves tissue remodelling. 
     
     
         19 : Use according to  claim 17 , wherein the component of the plasminogen-activating pathway is selected from plasminogen, Lys-plasminogen, Glu-plasminogen, plasmin, kringle domains of plasminogen and plasmin, mini-plasminogen, mini-plasmin, plasminogen activators, tPA, and uPA, or wherein the compound with the capacity to activate plasminogen directly or via the plasminogen-activating pathway is selected from streptokinase, saruplase, alteplase, reteplase, tenecteplase, anistreplase, monteplase, lanoteplase, pamiteplase, staphylokinase and recombinant forms and variants of the components of the plasminogen-activating pathway 
     
     
         20 : Use according to  claim 17 , wherein the subject is a human subject, and the component of the plasminogen-activating pathway is human plasminogen. 
     
     
         21 : Use according to  claim 17 , wherein the subject is a human subject, and the component of the plasminogen-activating-pathway is human plasmin. 
     
     
         22 : Use according to  claim 17 , wherein the subject is a non-human mammal. 
     
     
         23 . Use according to  claim 17 , wherein the administering is topical and the composition comprises from about 1 μg to about 500 mg plasminogen per square centimeter wound area. 
     
     
         24 : Use according to  claim 17 , wherein the administering is repeated at least once. 
     
     
         25 . Use according to  claim 24 , wherein the administering is repeated at least daily. 
     
     
         26 : Use according to  claim 17 , wherein the infectious periodontal wound is a wound caused by injury or a wound caused by periodontal surgery or plastic surgery. 
     
     
         27 : A pharmaceutical composition for the treatment, prophylaxis and/or prevention of infectious periodontal disease comprising an effective amount of a compound which is a component of the plasminogen-activating pathway or a compound which has the capacity to activate plasminogen directly or via the plasminogen-activating pathway. 
     
     
         28 : The composition according to  claim 27 , wherein the component of the plasminogen-activating pathway is selected from plasminogen, Lys-plasminogen, Glu-plasminogen, plasmin, kringle domains of plasminogen and plasmin, mini-plasminogen, mini-plasmin, plasminogen activators, tPA, and uPA, or wherein the compound with the capacity to activate plasminogen directly or via the plasminogen-activating pathway is selected from streptokinase, saruplase, alteplase, reteplase, tenecteplase, anistreplase, monteplase, lanoteplase, pamiteplase, staphylokinase and recombinant forms and variants of the components of the plasminogen-activating pathway 
     
     
         29 : The composition according to  claim 27 , wherein the component of the plasminogen-activating pathway is human plasminogen. 
     
     
         30 : The composition according to  claim 27 , wherein the component of the plasminogen-activating, pathway is human plasmin. 
     
     
         31 : Method for prophylaxis, prevention and/or treatment of infectious periodontal disease, comprising administering a pharmaceutical composition comprising an effective amount of a compound according to  claims 1 - 16 , which compound is a component of the plasminogen-activating pathway or which has the capacity to activate plasminogen directly or via the plasminogen-activating pathway to a subject in need of such treatment. 
     
     
         32 : Method according to  claim 31 , wherein the component of the plasminogen-activating pathway is selected from plasminogen, Lys-plasminogen, Glu-plasminogen, plasmin, kringle domains of plasminogen and plasmin, mini-plasminogen, mini-plasmin, plasminogen activators, tPA, and uPA or wherein the compound with the capacity to activate plasminogen directly or via the plasminogen-activating pathway is selected from streptokinase, saruplase, alteplase, reteplase, tenecteplase, anistreplase, monteplase, lanoteplase, pamiteplase, staphylokinase and recombinant forms and variants of the components of the plasminogen-activating pathway. 
     
     
         33 : Method according to  claim 31 , wherein the component of the plasminogen-activating pathway is human plasminogen. 
     
     
         34 : Method according to  claim 31 , wherein the component of the plasminogen-activating pathway is human plasinin. 
     
     
         35 : A pharmaceutical composition for promoting the healing of infectious periodontal wounds, which comprises an effective amount of a component of the plasminogen-activating pathway or an effective amount of a compound with the capacity to activate plasminogen directly or via the plasminogen-activating pathway. 
     
     
         36 : The pharmaceutical composition according to  claim 35 , wherein the component of the plasminogen-activating pathway is selected from plasminogen, Lys-plasminogen, Glu-plasminogen, plasmin, kringle domains of plasminogen and plasmin, mini-plasminogen, mini-plasmin, plasminogen activators, tPA, and uPA or wherein the compound h the capacity to activate plasminogen directly or via the plasminogen-activating pathway is selected from streptokinase, saruplase, alteplase, reteplase, tenecteplase, anistreplase, monteplase, lanoteplase, pamiteplase, staphylokinase and recombinant forms and variants of the components of the plasminogen-activating pathway. 
     
     
         37 : The pharmaceutical composition according to  claim 35 , wherein the component of the plasminogen-activating pathway is human plasminogen. 
     
     
         38 : The pharmaceutical composition according to  claim 35 , wherein the component of the plasminogen-activating pathway is human plasmin. 
     
     
         39 : Method for promoting the healing of infectious periodontal wounds, comprising administering a pharmaceutical composition comprising an effective amount of compound, which is a component of the plasminogen-activating pathway or which has the capacity to activate plasminogen directly or via the plasminogen-activating pathway to a subject in need of such treatment 
     
     
         40 : Method according to  claim 39 , wherein the component of the plasminogen-activating pathway is selected from plasminogen, Lys-plasminogen, Glu-plasminogen, plasmin, kringle domains of plasminogen and plasmin, mini-plasminogen, mini-plasmin, plasminogen activators, tPA, and uPA, or wherein the compound with the capacity to activate plasminogen directly or via the plasminogen-activating pathway is selected from streptokinase, saruplase, alteplase, reteplase, tenecteplase, anistreplase, monteplase, lanoteplase, pamiteplase, staphylokinase and recombinant forms and variants of the components of the plasminogen-activating pathway. 
     
     
         41 : Method according to  claim 39 , wherein the component of the plasminogen-activating pathway is human plasminogen. 
     
     
         42 . Method according to  claim 39 , wherein the component  31  of the plasminogen-activating pathway is human plasmin.