Soluble β-N-acetylglucosaminidase based antibiofilm compositions and uses thereof
View Patent ↗The present invention provides compositions comprising an antibiofilm enzyme, a soluble β-N-acetylglucosaminidase similar to the dspB gene (DispersinB®), and an antimicrobial for preventing growth and proliferation of biofilm-embedded microorganisms in acute and chronic wounds, and methods of treatment. The invention further provides methods for preparing medical devices, and in particular, wound care devices using soluble β-N-acetylglucosaminidase based antimicrobial compositions.
1. A composition for inhibiting biofilm-embedded microorganisms comprising: (a) amino acids 21-381 of SEQ ID NO:2, an active fragment or variant having at least 95% sequence identity thereof that disperses a biofilm; and (b) an antimicrobial agent.
2. The composition of claim 1 , wherein is in a concentration of about 1 μg/ml to about 500 μg/ml of the composition.
3. The composition of claim 1 , wherein the antimicrobial agent comprises triclosan, rifampicin, cefamandole nafate, nitrofurazone, bismuth thiol, bismuth ethanedithiol (BisEDT), ciprofloxacin, ovotransferrin, lactoferrin, sodium usnate, 5-fluorouracil, sodium dodecyl sulfate (SDS), chlorhexidine, benzalkonium chloride, EDTA, silver nanopowder, silver compounds, glucose oxidase, lactose peroxidase, cadexomer iodine, methylene blue, gentian violet, medium-chain dextrans, sugar alcohol, or mixtures thereof.
4. The composition of claim 3 , wherein the antimicrobial agent is triclosan.
5. The composition of claim 4 , wherein the triclosan is in a concentration of about 0.1 to about 100 mg/ml.
6. The composition of claim 3 , wherein the antimicrobial agent is nitrofurazone.
7. The composition of claim 3 , wherein the antimicrobial agent is 5-fluorouracil.
8. The composition of claim 3 , wherein the antimicrobial agent is EDTA.
9. The composition of claim 3 , wherein the antimicrobial agent is silver nanopowder.
10. The composition of claim 1 further comprising (c) a viscosity increasing agent.
11. The composition of claim 10 , wherein said amino acids 21-381 of SEQ ID NO:2, active fragment or variant having at least 95% sequence identity thereof, is about 0.001% to 0.1% by weight.
12. The composition of claim 10 , wherein the antimicrobial agent is selected from the group consisting of triclosan, rifampicin, cefamandole nafate, nitrofurazone, bismuth thiol, bismuth ethanedithiol (BisEDT), ciprofloxacin, ovotransferrin, lactoferrin, sodium usnate, 5-fluorouracil, sodium dodecyl sulfate (SDS), chlorhexidine, ber.kappa.alkonium chloride, HDTA, silver nanopowder, silver compounds, glucose oxidase, lactose peroxidase, cadexomer iodine, methylene blue, gentian violet, medium-chain dextrans, sugar alcohol, and mixtures thereof.
13. The composition of claim 12 , wherein the antimicrobial agent is triclosan.
14. The composition of claim 13 , wherein the triclosan is about 0.1% to about 10% by weight.
15. The composition of claim 10 , further comprising polyethylene glycol (PEG).
16. The composition of claim 1 , wherein the composition is in the form of a formable or pliable putty or flexible sheets that can be readily molded and cut into shape.
17. A wound dressing or covering comprising the composition of claim 1 .
18. A method of inhibiting biofilm-embedded microorganisms comprising administering an effective amount of the composition of claim 1 .
19. The method of claim 18 , wherein the antimicrobial agent comprises triclosan, rifampicin, cefamandole nafate, nitrofurazone, bismuth thiol, bismuth ethanedithiol (BisEDT), ciprofloxacin, ovotransferrin, lactoferrin, sodium usnate, 5-fluorouracil, sodium dodecyl sulfate (SDS), chlorhexidine, benzalkonium chloride, EDTA, silver nanopowder, silver compounds, glucose oxidase, lactose peroxidase, cadexomer iodine, methylene blue, gentian violet, medium-chain dextrans, sugar alcohol, or mixtures thereof.
20. The method of claim 18 , wherein said amino acids 21-381 of SEQ ID NO:2, active fragment or variant having at least 95% sequence identity thereof is administered prior to administration of the antimicrobial agent and wherein the antimicrobial agent comprises sodium dodecyl sulfate, chlorhexidine, or benzalkonium chloride.