Compositions for Treating Biofilms and Methods for Using Same

Abstract

Compositions containing a surface active agent and a sub-lethal amount of an antimicrobial agent and methods for using such compositions are provided herein.

1 . A method for treating a microbial biofilm on a patient comprising contacting the microbial biofilm with a composition comprising a surface active agent and a sub-lethal amount of an antimicrobial agent. 
   
   
       2 . The method of  claim 1 , wherein the antimicrobial agent is selected from an antibacterial, antifungal, antiviral or combinations thereof. 
   
   
       3 . The method of  claim 1 , wherein the antimicrobial agent is selected from furaltadone, furazolium chloride, nifuradene, nifuratel, nifurfoline, nifurpirinol, nifurprazine, nifurtoinol, nitrofurantoin, furazolidone, 2-(methoxymethyl)-5-nitrofuran, nidroxyzone, nifuroxime, nifurazide, nitrofurazone, nystatin, polymyxin, silver sulfadiazine, nanocrystalline silver, ionic silver, honey, iodine, benzalkonium chloride, alcohol, hydrogen peroxide, chlorhexidine and combinations thereof. 
   
   
       4 . The method of  claim 1 , wherein a sub-lethal amount of an antimicrobial agent is a standard therapeutically effective amount. 
   
   
       5 . The method of  claim 1 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 1% by weight of the composition. 
   
   
       6 . The method of  claim 1 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.95% by weight of the composition. 
   
   
       7 . The method of  claim 1 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.75% by weight of the composition. 
   
   
       8 . The method of  claim 1 , wherein the surface active agent is selected from a poloxamer, meroxapol, poloxamine and combinations thereof. 
   
   
       9 . The method of  claim 1 , wherein the surface active agent is selected from a poloxamer 127, poloxamer 188, poloxamer 237, poloxamer 335, poloxamer 407 and combinations thereof. 
   
   
       10 . The method of  claim 1 , wherein the surface active agent is poloxamer 188. 
   
   
       11 . The method of  claim 1 , wherein contacting the microbial biofilm comprises applying the composition to a wound. 
   
   
       12 . The method of  claim 1 , wherein contacting the microbial biofilm comprises administering the composition topically. 
   
   
       13 . The method of  claim 12 , wherein administering the composition topically is selected from administering by hand, administering by an extruder, spray delivery, applying a dressing including the composition and combinations thereof. 
   
   
       14 . The method of  claim 1 , wherein contacting the microbial biofilm comprises contacting tissue from the patient that is outside the patient. 
   
   
       15 . The method of  claim 1 , wherein contacting comprises applying the composition to a dressing prior to applying the dressing to the patient. 
   
   
       16 . The method of  claim 1 , wherein the patient is afflicted with an injury. 
   
   
       17 . The method of  claim 16 , wherein the injury is selected from a burn, abrasion, cut, scrape, denuding tissue injury and combinations thereof. 
   
   
       18 . The method of  claim 1 , wherein the patient is afflicted with a chronic wound. 
   
   
       19 . The method of  claim 18 , wherein chronic wound is selected from a venous ulcer, diabetic ulcer, arterial ulcer, pressure ulcer, radiation ulcer, traumatic wound, non-healing wound and combinations thereof. 
   
   
       20 . A method for preventing a microbial biofilm on a patient comprising administering a composition comprising a surface active agent and a sub-lethal amount of an antimicrobial agent to an injury. 
   
   
       21 . The method of  claim 20 , wherein the antimicrobial agent is selected from an antibacterial, antifungal, antiviral or combinations thereof. 
   
   
       22 . The method of  claim 20 , wherein the antimicrobial agent is selected from furaltadone, furazolium chloride, nifuradene, nifuratel, nifurfoline, nifurpirinol, nifurprazine, nifurtoinol, nitrofurantoin, furazolidone, 2-(methoxymethyl)-5-nitrofuran, nidroxyzone, nifuroxime, nifurazide, nitrofurazone, nystatin, polymyxin, silver sulfadiazine, silver salts, iodine, benzalkonium chloride, alcohol, hydrogen peroxide, chlorhexidine and combinations thereof. 
   
   
       23 . The method of  claim 20 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 1% by weight of the composition. 
   
   
       24 . The method of  claim 20 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.95% by weight of the composition. 
   
   
       25 . The method of  claim 20 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.75% by weight of the composition. 
   
   
       26 . The method of  claim 20 , wherein the surface active agent is selected from a poloxamer, meroxapol, poloxamine and combinations thereof. 
   
   
       27 . The method of  claim 20 , wherein the surface active agent is a copolymer selected from a poloxamer 127, poloxamer 188, poloxamer 237, poloxamer 335, poloxamer 407 and combinations thereof. 
   
   
       28 . The method of  claim 20 , wherein the surface active agent is poloxamer 188. 
   
   
       29 . The method of  claim 20 , wherein administering comprises applying the composition to a wound. 
   
   
       30 . The method of  claim 20 , wherein administering comprises administering the composition topically. 
   
   
       31 . The method of  claim 30 , wherein administering the composition topically is selected from administering by hand, administering by an extruder, spray delivery, applying a dressing including the composition and combinations thereof. 
   
   
       32 . The method of  claim 20 , wherein administering comprises contacting tissue from the patient that is outside the patient. 
   
   
       33 . The method of  claim 20 , wherein administering comprises applying the composition to a dressing prior to applying the dressing to the patient. 
   
   
       34 . The method of  claim 20 , wherein the injury is selected from a burn, abrasion, cut, scrape, denuding tissue injury and combinations thereof. 
   
   
       35 . The method of  claim 20 , wherein the composition is administered while biofilm forming pathogens are in a planktonic state. 
   
   
       36 . A method for treating or preventing a microbial biofilm in a patient comprising:
 administering a first composition comprising a surface active agent to an injury wherein the first composition does not contain an antimicrobial agent; and   administering a second composition comprising a surface active agent and a sub-lethal amount of an antimicrobial agent to the injury;   wherein the first composition is administered before the second composition.   
   
   
       37 . The method of  claim 36 , wherein the second composition is applied to a dressing prior to its administration. 
   
   
       38 . The method of  claim 36 , wherein the antimicrobial agent of the second composition is selected from an antibacterial, an antifungal, an antiviral or a combination thereof. 
   
   
       39 . The method of  claim 36 , wherein the antimicrobial agent of the second composition is selected from furaltadone, furazolium chloride, nifuradene, nifuratel, nifurfoline, nifurpirinol, nifurprazine, nifurtoinol, nitrofurantoin, furazolidone, 2-(methoxymethyl)-5-nitrofuran, nidroxyzone, nifuroxime, nifurazide, nitrofurazone, nystatin, polymyxin, silver sulfadiazine silver salts, nanocrystalline silver, ionic silver, iodine, benzalkonium chloride, alcohol, hydrogen peroxide, chlorhexidine and combinations thereof. 
   
   
       40 . The method of  claim 36 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 1% by weight of the composition. 
   
   
       41 . The method of  claim 36 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.95% by weight of the composition. 
   
   
       42 . The method of  claim 36 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.75% by weight of the composition. 
   
   
       43 . The method of  claim 36 , wherein the surface active agents in the first and second composition are surfactants. 
   
   
       44 . The method of  claim 36 , wherein the surface active agents in the first and second compositions are independently selected from poloxamer 127, poloxamer 188, poloxamer 237, poloxamer 335, poloxamer 407 and combinations thereof. 
   
   
       45 . The method of  claim 36 , wherein the surface active agents in the first and second compositions are the same. 
   
   
       46 . The method of  claim 36 , wherein the surface active agents in the first and second compositions are poloxamer 188. 
   
   
       47 . A composition for treating or preventing a microbial biofilm comprising:
 a surface active agent; and   a sub-lethal amount of an antimicrobial agent.   
   
   
       48 . The composition of  claim 47 , wherein the antimicrobial agent is selected from an antibacterial, an antifungal, an antiviral or a combination thereof. 
   
   
       49 . The composition of  claim 47 , wherein the antimicrobial agent is selected from furaltadone, furazolium chloride, nifuradene, nifuratel, nifurfoline, nifurpirinol, nifurprazine, nifurtoinol, nitrofurantoin, furazolidone, 2-(methoxymethyl)-5-nitrofuran, nidroxyzone, nifuroxime, nifurazide, nitrofurazone, nystatin, polymyxin, silver sulfadiazine, nanocrystalline silver, ionic silver, silver salts, iodine, benzalkonium chloride, alcohol, hydrogen peroxide, chlorhexidine, honey and combinations thereof. 
   
   
       50 . The composition of  claim 47 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 1% by weight of the composition. 
   
   
       51 . The composition of  claim 47 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.95% by weight of the composition. 
   
   
       52 . The composition of  claim 47 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.75% by weight of the composition. 
   
   
       53 . The composition of  claim 47 , wherein the composition further comprises a solvent. 
   
   
       54 . The composition of  claim 47 , wherein the surface active agent is selected from a poloxamer, meroxapol, poloxamine and combinations thereof. 
   
   
       55 . The composition of  claim 54 , wherein the poloxamer is selected from a poloxamer 101, poloxamer 105, poloxamer 105 benzoate, poloxamer 108, poloxamer 122, poloxamer 123, poloxamer 124, poloxamer 181, poloxamer 182, poloxamer 182 dibenzoate, poloxamer 183, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 212, poloxamer 215, poloxamer 217, poloxamer 231, poloxamer 234, poloxamer 235, poloxamer 237, poloxamer 238, poloxamer 282, poloxamer 284, poloxamer 288, poloxamer 331, poloxamer 333, poloxamer 334, poloxamer 335, poloxamer 338, poloxamer 401, poloxamer 402, poloxamer 403 and poloxamer 407 and combinations thereof. Agent is a copolymer selected from poloxamer 127, poloxamer 188, poloxamer 237, poloxamer 335, poloxamer 407 and combinations thereof. 
   
   
       56 . The composition of  claim 53 , wherein the surface active agent is poloxamer 188. 
   
   
       57 . The composition of  claim 54 , wherein the meroxapol is selected from a meroxapol 105, meroxapol 108, meroxapol 171, meroxapol 172, meroxapol 174, meroxapol 178, meroxapol 251, meroxapol 252, meroxapol 254, meroxapol 258, meroxapol 311, meroxapol 312, meroxapol 314 and combinations thereof. 
   
   
       58 . The composition of  claim 54 , wherein the poloxamine is selected from a poloxamine 304, poloxamine 504, poloxamine 701, poloxamine 702, poloxamine 704, poloxamine 707, poloxamine 901, poloxamine 904, poloxamine 908, poloxamine 1101, poloxamine 1102, poloxamine 1104, poloxamine 1301, poloxamine 1302, poloxamine 1304, poloxamine 1307, poloxamine 1501, poloxamine 1502, poloxamine 1504, poloxamine 1508 and combinations thereof. 
   
   
       59 . The composition of  claim 47 , further comprising one or more secondary active agents. 
   
   
       60 . The composition of  claim 47 , further comprising one or more additives. 
   
   
       61 . A dressing for treating or preventing a microbial biofilm comprising:
 a first composition layer comprising a surface active agent wherein the first gel layer does not include an antimicrobial agent;   a second composition layer comprising a surface active agent and a sub-lethal amount of an antimicrobial agent; and   a dressing material supporting said first and second composition layers;   wherein the second composition layer is located between the first composition layer and the dressing material.   
   
   
       62 . The dressing of  claim 61 , wherein the antimicrobial agent is selected from an antibacterial, an antifungal, an antiviral or a combination thereof. 
   
   
       63 . The dressing of  claim 61 , wherein the antimicrobial agent is selected from furaltadone, furazolium chloride, nifuradene, nifuratel, nifurfoline, nifurpirinol, nifurprazine, nifurtoinol, nitrofurantoin, furazolidone, 2-(methoxymethyl)-5-nitrofuran, nidroxyzone, nifuroxime, nifurazide, nitrofurazone, nystatin, polymyxin, silver sulfadiazine, nanocrystalline silver, ionic silver, silver salts, iodine, benzalkonium chloride, alcohol, hydrogen peroxide, chlorhexidine, honey and combinations thereof. 
   
   
       64 . The dressing of  claim 61 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 1% by weight of the composition. 
   
   
       65 . The dressing of  claim 61 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.95% by weight of the composition. 
   
   
       66 . The dressing of  claim 61 , wherein the antimicrobial agent is silver sulfadiazine and the sub-lethal amount is less than about 0.75% by weight of the composition. 
   
   
       67 . The dressing of  claim 61 , wherein the surface active agent in the first and second compositions is selected from a poloxamer, meroxapol, poloxamine and combinations thereof. 
   
   
       68 . The dressing of  claim 61 , wherein the surface active agent in the first and second compositions is independently selected from a poloxamer 127, poloxamer 188, poloxamer 237, poloxamer 335, poloxamer 407 and combinations thereof. 
   
   
       69 . The dressing of  claim 61 , wherein the surface active agent in the first and second compositions is poloxamer 188. 
   
   
       70 . The dressing of  claim 61 , wherein the surface active agent in the first and second compositions is the same. 
   
   
       71 . The dressing of  claim 61 , further comprising a spacer material layer between said first and second composition layers. 
   
   
       72 . The dressing of  claim 71 , wherein the spacer material fully or partially loses integrity upon application of the dressing to a patient. 
   
   
       73 . The dressing of  claim 61 , wherein the second composition layer impregnates the dressing material. 
   
   
       74 . A method for treating or preventing a microbial biofilm on a patient comprising administering a composition comprising a surface active agent and a sub-lethal amount of an antimicrobial agent to a wound prior to infection. 
   
   
       75 . A method for treating or preventing a microbial biofilm on a patient comprising administering a composition comprising a surface active agent and a sub-lethal amount of an antimicrobial agent to a wound while biofilm forming bacteria are in a planktonic state. 
   
   
       76 . A method for treating or preventing a microbial biofilm on a patient comprising administering a composition comprising a surface active agent and a sub-lethal amount of an antimicrobial agent to a wound prior to infection wherein the composition is administered within 10 hours of the injury. 
   
   
       77 . A method for treating or preventing a microbial biofilm comprising administering a composition comprising a surface active agent to a wound.