Inhibition of biofilm organisms

Abstract

The present invention relates to a product comprising at least two antibiofilm agents wherein at least one of the antibiofilm agents is an antimicrobial peptide. The second antibiofilm agent is cysteamine. There is also provided the use of the product in the treatment of a microbial infection.

1 . A product comprising at least two antibiofilm agents wherein at least one of the antibiofilm agents is an antimicrobial peptide. 
     
     
         2 . A product as claimed in  claim 1  wherein the other antibiofilm agent is a dispersant or an anti-adhesive agent. 
     
     
         3 . A product as claimed in  claim 1  or  claim 2  wherein the antimicrobial peptide is an antibacterial peptide. 
     
     
         4 . A product as claimed in any preceding claim wherein the antimicrobial peptide comprises amino acids according to the formula I:
   ((X) l (Y) m ) n   (I)
   wherein l and m are integers from 1 to 10, for example 1 to 5; n is an integer from 1 to 10;   X and Y, which may be the same or different, are independently a hydrophobic or cationic amino acid.   
     
     
         5 . A product as claimed in  claim 4  wherein the antimicrobial peptide comprises amino acids according to the formula (I) wherein X and Y are cationic amino acids. 
     
     
         6 . A product as claimed in any preceding claim wherein the antimicrobial peptide comprises between 2 and 200 amino acids. 
     
     
         7 . A product as claimed in any preceding claim wherein X and/or Y are cationic amino acids. 
     
     
         8 . A product as claimed in  claim 7  wherein X and/or Y are selected from the group consisting of histidine, arginine and lysine. 
     
     
         9 . A product as claimed in  claim 8  wherein X and/or Y are selected from arginine and lysine. 
     
     
         10 . A product as claimed in any of  claims 2  to  9  wherein the dispersant is an agent capable of dispersing the particles of a biofilm. 
     
     
         11 . A product as claimed in  claim 10  wherein the dispersant is a mucolytic agent. 
     
     
         12 . A product as claimed in any of  claims 10  to  12  wherein the dispersant is an enzyme. 
     
     
         13 . A product as claimed in  claim 12  wherein the enzyme is selected from the group consisting of DNase, alginase, protease and carobohydrase. 
     
     
         14 . A product as claimed in any of  claims 10  to  12  wherein the dispersant is an amine. 
     
     
         15 . A product as claimed in  claim 14  wherein the amine is an aminothiol. 
     
     
         16 . A product as claimed in  claim 15  wherein the amine is selected from acetylcysteine and cysteamine. 
     
     
         17 . A product as claimed in any of  claims 10  to  12  wherein the dispersant is an acid. 
     
     
         18 . A product as claimed in  claim 17  wherein the acid is ethylenediaminetetraacetic acid (EDTA). 
     
     
         19 . A product as claimed in any of  claims 2  to  9  wherein the anti-adhesive agent is an agent capable of inhibiting adhesion between cells, proteins and organisms 
     
     
         20 . A product as claimed in  claim 19  wherein the anti-adhesive agent is selected from the group consisting of hyaluronan, heparin and Carbopol 934. 
     
     
         21 . A product as claimed in any preceding claim comprising a synergistically effective amount of (i) a first antibiofilm agent, and (ii) a second antibiofilm agent wherein the second antibiofilm agent is different from the first antibiofilm agent and is an antimicrobial peptide. 
     
     
         22 . A product as claimed in any preceding claim for use as a disinfectant or biocide. 
     
     
         23 . A product as claimed in any of  claims 1  to  21  for use as a medicament. 
     
     
         24 . A substrate to which a product as claimed in any preceding claim is applied or attached. 
     
     
         25 . A substrate as claimed in  claim 24  wherein the substrate is selected from the group consisting of dressings, medical devices and indwelling devices. 
     
     
         26 . A substrate as claimed in  claim 25  wherein the indwelling device is selected from the group consisting of stents, catheters, peritoneal dialysis tubing, draining devices, joint prostheses and dental implants. 
     
     
         27 . A pharmaceutical composition comprising a product as claimed in any of  claims 1  to  21  and one or more pharmaceutically acceptable diluents, excipients and/or carriers. 
     
     
         28 . Use of a product as claimed in any of  claims 1  to  21  in the treatment of a microbial infection or disease or condition associated therewith. 
     
     
         29 . Use of an antimicrobial peptide comprising amino acids according to the formula I in the treatment of a microbial infection or disease or condition associated therewith. 
     
     
         30 . The use as claimed in either one of  claims 28  and  29  wherein infection, or disease or condition associated therewith, is selected from the group consisting of skin and wound infections, middle-ear infections, gastrointestinal tract infections, peritoneal membrane infections, urogenital tract infections, oral soft tissue infections, formation of dental plaque, eye infections, endocarditis, infections in cystic fibrosis, and infections of indwelling medical devices. 
     
     
         31 . A method of preventing biofilm formation in an environment comprising the step of administering to the environment a product as claimed in any of  claims 1  to  21  or a substrate as claimed in any of  claims 24  to  26 . 
     
     
         32 . A method of preventing biofilm formation in an environment comprising the step of administering to the environment an antimicrobial peptide comprising amino acids according to formula I. 
     
     
         33 . A method as claimed in either one of  claims 31  and  32  wherein the environment comprise a biofilm forming microorganism selected from bacteria, fungi, yeast, viruses and protozoa. 
     
     
         34 . A method as claimed in  claim 33  wherein the microorganism is a bacterium. 
     
     
         35 . A method as claimed in  claim 34  wherein the bacterium is selected from the group consisting of may include  Pseudomonas  spp.,  Staphylococcus  spp.,  Haemophilus  spp.,  Burkholderia  spp.,  Streptococcus  spp.,  Propionibacterium  spp. 
     
     
         36 . A method as claimed in  claim 35  wherein the bacterium is selected from  Pseudomonas  spp., and  Staphylococcus  spp. 
     
     
         37 . A method as claimed in  claim 36  wherein the bacterium is  Pseudomonas aeruginosa, Staphylococcus aureus  or  Staphylococcus epidermidis.    
     
     
         38 . A method as claimed in any of  claims 32  to  37  wherein the environment is the mouth. 
     
     
         39 . A method as claimed in  claim 38  for the prevention of the formation of plaque or caries on a human tooth or dental implant. 
     
     
         40 . A method of treating a microbial infection by prophylaxis or therapy comprising the sequential or combined administration in a therapeutically effective amount of:
 a first antibiofilm agent; and   a second antibiofilm agent different from the first one; wherein at least one of the first and second antibiofilm agents is an antimicrobial peptide.   
     
     
         41 . A method as claimed in  claim 40  wherein the first antibiofilm agent is an antimicrobial peptide and the second antibiofilm agent is selected from a dispersant and an anti-adhesive agent. 
     
     
         42 . A method as claimed in  claim 40  or  41  wherein the microbial infection is a topical infection. 
     
     
         43 . A method as claimed in  claim 42  wherein the topical infection is selected from a wound, ulcer and lesion. 
     
     
         44 . A method as claimed in  claim 40  or  41  wherein the microbial infection is an oral infection. 
     
     
         45 . A method as claimed in  claim 44  wherein the oral infection is selected from gingivitis, periodontitis and mucositis. 
     
     
         46 . A method as claimed in  claim 40  or  41  wherein the microbial infection is a systemic infection. 
     
     
         47 . A method as claimed in  claim 46  wherein the systemic infection is a mucosal infection. 
     
     
         48 . A method as claimed in  claim 47  wherein the mucosal infection is a gastrointestinal, urogenital or respiratory infection. 
     
     
         49 . A method as claimed in  claim 47  or  48  wherein the mucosal infection is cystic fibrosis. 
     
     
         50 . A method of treating or preventing biofilm formation in an environment comprising administering to said environment an effective amount of cysteamine. 
     
     
         51 . Use of a cysteamine, in the treatment of a microbial infection, particularly a microbial biofilm infection.