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.

1 - 42 . (canceled) 
   
   
       43 . A method of prophylaxis, prevention and/or treatment of infectious periodontal disease comprising administering a pharmaceutical composition comprising a compound selected from the group consisting of plasminogen, Lys-plasminogen, Glu-plasminogen, variants of plasminogen comprising one or more of the kringle domains and the proteolytic domain, mini-plasminogen, and kringle domains of plasminogen in an effective amount to a subject in need of thereof. 
   
   
       44 . Method of  claim 43 , wherein the periodontal disease is, or is caused by, a bacterial infection. 
   
   
       45 . Method of  claim 43 , wherein the periodontal disease is selected from the group consisting of periodontitis, gingivitis, necrotizing gingivitis, periimplantitis, and peri-implant mucositis. 
   
   
       46 . Method of  claim 43 , wherein the subject is a human, and the compound is human plasminogen. 
   
   
       47 . Method of  claim 43 , wherein the subject is a non-human mammal. 
   
   
       48 . Method of  claim 43 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier. 
   
   
       49 . Method of  claim 43 , wherein the pharmaceutical 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, and a wound dressing. 
   
   
       50 . Method of  claim 43 , wherein the pharmaceutical composition is administered by a method selected from the group consisting of spray, topical, oral, local, and systemic administration. 
   
   
       51 . Method of  claim 50 , wherein the pharmaceutical composition for topical administration comprises from about 1 μg to about 500 mg plasminogen per square centimeter of the application area. 
   
   
       52 . Method of  claim 43 , wherein the administering is repeated at least once. 
   
   
       53 . Method of  claim 52 , wherein the administering is repeated daily. 
   
   
       54 . Method of  claim 43 , further comprising a step selected from the group consisting of activating inflammatory cells, enhancing keratinocyte migration, reducing bacterial growth, removing necrotic tissue, improving tissue remodeling, and enhancing cytokine expression. 
   
   
       55 . A pharmaceutical composition for the treatment, prophylaxis and/or prevention of infectious periodontal disease caused by bacterial, viral or fungal infection comprising an effective amount of a compound selected from the group consisting of plasminogen, Lys-plasminogen, Glu-plasminogen, variants of plasminogen comprising one or more of the kringle domains and the proteolytic domain, mini-plasminogen, and kringle domains of plasminogen. 
   
   
       56 . The pharmaceutical composition according to  claim 55 , wherein the compound is human plasminogen. 
   
   
       57 . A method of promoting the healing of infectious periodontal wounds comprising administering a pharmaceutical composition comprising a compound selected from the group consisting of plasminogen, Lys-plasminogen, Glu-plasminogen, variants of plasminogen comprising one or more of the kringle domains and the proteolytic domain, mini-plasminogen, and kringle domains of plasminogen in an effective amount to a subject in need thereof. 
   
   
       58 . Method of  claim 57 , wherein the infectious periodontal wound is a wound caused by injury or a wound caused by periodontal surgery or plastic surgery. 
   
   
       59 . Method of  claim 57 , wherein the subject is a human, and the compound is human plasminogen. 
   
   
       60 . Method of  claim 57 , wherein the subject is a non-human mammal. 
   
   
       61 . Method of  claim 57 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier. 
   
   
       62 . Method of  claim 57 , wherein the pharmaceutical 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, and a wound dressing. 
   
   
       63 . Method of  claim 57 , wherein the pharmaceutical composition is administered by a method selected from the group consisting of spray, topical, oral, local, and systemic administration. 
   
   
       64 . Method of  claim 63 , wherein the pharmaceutical composition for topical administration comprises from about 1 μg to about 500 mg plasminogen per square centimeter of the application area. 
   
   
       65 . Method of  claim 57 , wherein the administering is repeated at least once. 
   
   
       66 . Method of  claim 65 , wherein the administering is repeated daily. 
   
   
       67 . Method of  claim 57 , further comprising a step selected from the group consisting of reducing fibrin deposition, promoting keratinocyte migration, enhancing cytokine expressions, removing necrotic tissue, activating inflammatory cells, and improving tissue remodeling. 
   
   
       68 . A pharmaceutical composition for promoting the healing of infectious periodontal wounds, which comprises an effective amount of a compound selected from the group consisting of plasminogen, Lys-plasminogen, Glu-plasminogen, variants of plasminogen comprising one or more of the kringle domains and the proteolytic domain, mini-plasminogen, and kringle domains of plasminogen. 
   
   
       69 . The pharmaceutical composition according to  claim 68 , wherein the compound is human plasminogen.