Pharmaceutical composition, substrate comprising a pharmaceutical composition, and use of a pharmaceutical composition

Abstract

Use of a pharmaceutical composition for the local treatment or prevention of a tissue infection at an infection site, the pharmaceutical composition comprising at least two different antibiotics of group A or pharmaceutically acceptable derivatives thereof, or an antibiotic of group A and at least one antibiotic of group B or pharmaceutically acceptable derivatives thereof. Group A comprises primarily intracellular active antibiotics working as inhibitor of bacterial RNA polymerase; as inhibitor of gyrase; or as inhibitor of bacterial protein synthesis. Group B comprises primarily extracellular active antibiotics working as inhibitor of bacterial cell wall synthesis; or inhibitor of bacterial protein synthesis; or by direct destabilisation or rupture of the bacterial cell wall.

1 . A pharmaceutical composition for use in the local treatment and prevention of a tissue infection, the pharmaceutical composition comprising a rifamycin and fosfomycin or a rifamycin and daptomycin in a coating, wherein the coating comprises 10 to 1000 μg/cm 2  antibiotics. 
     
     
         2 . The composition according to  claim 1 , characterized in that the rifamycin is rifampin, rifabutin, rifapentine or rifamixin. 
     
     
         3 . The composition according to  claim 1 , characterized in that, said composition comprises rifampin and fosfomycin. 
     
     
         4 . The composition according to  claim 1 , characterized in that said composition further comprises a biofilm formation inhibitor. 
     
     
         5 . The composition according to  claim 4 , characterized in that the biofilm formation inhibitor comprises salicylic acid or a pharmaceutically acceptable derivative or salt thereof. 
     
     
         6 . The composition according to  claim 1  characterized in that the infected tissue to be treated is acutely or chronically infected. 
     
     
         7 . The composition according to  claim 1 , characterized in that said composition is used in the treatment of extracellular and/or intracellular microbial infected tissue cells and/or for the prevention of extracellular and/or intracellular microbial infections of tissue cells. 
     
     
         8 . The composition according to  claim 7 , characterized in that the infected tissue cells are soft tissue cells and/or bone tissue cells. 
     
     
         9 . The composition according to  claim 8 , characterized in that the infected tissue soft tissue cells and/or bone tissue cells are osteoblasts, leucocytes, erythrocytes, keratinocytes, fibroblasts, fat cells, muscle cells and/or endothelial cells. 
     
     
         10 . Composition according to  claim 7 , characterized in that the tissue infection is caused by gram-negative and/or gram-positive bacteria, preferably by the Staphyloccoci type, most preferably by  Staphylococcus aureus.    
     
     
         11 . The composition according to  claim 1 , characterized in that said composition comprises rifamycin and fosfomycin in such a concentration that the rifamycin reaches a concentration of 0.005 to 100 μg/ml, preferably 0.006 to 80 μg/ml, most preferably 0.0075 to 10 μg/ml at the site to be treated, and fosfomycin reaches a concentration of 1 to 1000 μg/ml, preferably 5 to 800 μg/ml, most preferably 10 to 200 μg/ml fosfomycin at the site to be treated. 
     
     
         12 . The composition according to  claim 1 , characterized in that said composition comprises rifamycin and daptomycin in such a concentration that the rifamycin reaches a concentration of 0.005 to 100 μg/ml, preferably 0.006 to 80 μg/ml, most preferably 0.0075 to 20 μg/ml at the site to be treated, and daptomycin reaches a concentration of 0.1 to 100 μg/ml, preferably 0.5 to 80 μg/ml, most preferably 1 to 20 μg/ml at the site to be treated. 
     
     
         13 . The composition according to  claim 1 , characterized in that the coating comprises a substrate arranged and provided for being used as carrier of said composition, in particular for local antibiotic therapy of an acute or chronic infection of a tissue of a subject. 
     
     
         14 . Composition according to  claim 13 , characterized in that said substrate comprises a fleece, a fabric, a polymethyl methacrylate, a copolymer of methylmethacrylate and methylacrylate, a biodegradable polymer, polyethylene, a metal, a ceramic, a bone cement, a bone substitute, or a combination of any of the foregoing. 
     
     
         15 . The composition according to  claim 14 , characterized in that the fleece or the fabric comprises a natural or synthetic fibre, particularly polylactide, and/or collagen. 
     
     
         16 . The composition according to  claim 13 , characterized in that said substrate comprises an implantable prosthesis, in particular a hip prosthesis, a shoulder prosthesis, an elbow prosthesis, a knee prosthesis, a vertebral implant, or an implant for trauma surgery.