Synergistic antimicrobial compositions and methods of inhibiting biofilm formation

• US 20050049181A1
• Filed: 02/17/2004
• Published: 03/03/2005
• Est. Priority Date: 08/25/2003
• Status: Active Grant

• Current Assignee: Kane Biotech Inc.
• Original Assignee: Kane Biotech Inc.
• Inventors: Madhyastha, Srinivasa
• Granted Patent: US 7,314,857 B2
• Time in Patent Office: Days
• US Class Current: 514/2.400
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 37/44 containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
• CPC Class Codes: A01N 43/16 with oxygen as the ring hetero atom
• CPC Class Codes: A01N 61/00 Biocides, pest repellants or attractants, or plant growth regulators containing substances of unknown or undetermined composition, e.g. substances characterised only by the mode of action
• CPC Class Codes: A01N 63/50 Isolated enzymes; Isolated proteins peptides A01N37/46
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/048 Other specific proteins or polypeptides not covered by A61L29/045 - A61L29/047
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61P 31/04 Antibacterial agents

Abstract

A synergistic antimicrobial composition for inhibiting biofilm formation includes an iron-sequestering glycoprotein, a cationic polypeptide and a chelating agent, or an iron-sequestering glycoprotein and a chelating agent, or an iron-sequestering glycoprotein and a cationic polypeptide. Additionally, surfactants and quaternary ammonium compounds may also be advantageously combined with iron-sequestering glycoproteins in an antimicrobial composition. Methods of using a synergistic composition for inhibiting medical device biofilm formation are also disclosed.

Claims

1. A composition for inhibiting bacterial biofilm on devices selected from the group comprising:

(a) an iron-sequestering glycoprotein, a cationic polypeptide, and a chelating agent;

(b) an iron-sequestering glycoprotein and a cationic polypeptide; and

(c) an iron-sequestering glycoprotein and a chelating agent.

2. The composition of claim 1, wherein the iron-sequestering glycoprotein is between about 125 mg/L and about 2000 mg/L of the composition.

3. The composition of claim 1, wherein the cationic polypeptide is between about 12.5 mg/L and about 200 mg/L of the composition.

4. The composition of claim 1, wherein the chelating agent is between about 12.5 mg/L and about 200 mg/L of the composition.

5. The composition of claim 1, wherein the composition is effective against biofilms produced by bacterial species selected from the group consisting of Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus epidermidis.

6. The composition of claim 1, wherein the composition is effective against biofilms produced by gram-negative bacterial species selected from the group consisting of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae and Pseudomonas aeruginosa.

7. The composition of claim 1, wherein the composition is effective against biofilms produced by gram-positive bacterial species selected from the group consisting of Enterococcus faecalis and Staphylococcus epidermidis.

8. The composition of claim 1, wherein the iron sequestering glycoprotein selected from the group consisting of ovotransferrin, lactoferrin and serotransferrin.

9. The composition of claim 1, wherein the cationic polypeptide is selected from the group consisting of protamine sulfate, polylysine, defensin, lactoperoxidase and lysozyme.

10. The composition of claim 1, wherein the chelating agent is selected from the group consisting of EDTA, EGTA, DTPA, EDDHA, IDA, CDTA, HEDTA, HEIDA and NTA.

11. The composition of claim 1, further comprising one or more ingredients selected from the group consisting of:

water, a binding or bonding or coupling agent, a surfactant, a quaternary ammonium compound, an antibiotic and a pH adjuster.

12. The composition of claim 1, wherein the iron-sequestering agent is ovotransferrin, the cationic polypeptide is protamine sulfate, and the chelating agent is EDTA.

13. The composition of claim 12, wherein the ovotransferrin is present as about 2 mg/ml, the protamine sulfate is present as about 0.2 mg/ml, and the EDTA is present as about 0.2 mg/ml.

14. The composition of claim 13, wherein the composition further comprises water.

15. A method of preparing a device comprising treating at least a surface of the device with the composition of claim 1.

16. The method as claimed in claim 15 wherein the composition comprises effective amounts of ovotransferrin, protamine sulfate and EDTA.

17. The method of preparing a device comprising coating a device with the composition of claim 1.

18. The method as claimed in claim 17 wherein the composition comprises effective amounts of ovotransferrin, protamine sulfate and EDTA.

19. The method as claimed in claim 17 wherein the method comprises treating the device with quaternary ammonium compound before coating the device with the composition.

20. The method as claimed in claim 19 wherein the quaternary ammonium compound is selected from the group consisting of tridodecylmethyl ammonium chloride and benzalkonium chloride.

21. The method as claimed in claim 17 wherein the composition further comprises hydrogel.

22. The method as claimed in claim 19, further comprising coating the device with a hydrogel selected from the group consisting of polyvinylpyrrolidone-hydrogel, polyvinyl alcohol-hydrogel and polyethylene glycol-hydrogel.

23. The method as claimed in claim 15, wherein the device is a medical device.

24. The method as claimed in claim 23, wherein the device is a catheter.

25. The method of claim 24, wherein the catheter is an indwelling catheter.

26. The method of claim 24, wherein the indwelling catheter is selected from a group consisting of a central venous catheter, a peripheral intravenous catheter, an arterial catheter, a haemodialysis catheter, an umbilical catheter, precutaneous nontunneled silicone catheter, a cuffed tunneled central venous catheter and a subcutaneous central venous port.

27. The method of claim 24, wherein the indwelling catheter is selected from a group consisting of urinary catheter and a peritoneal catheter.

28. The method as claimed in claim 23, wherein the device selected from the group consisting of catheters, pacemakers, prosthetic heart valves, prosthetic joints, voice prostheses, contact lenses, and intrauterine devices.

29. The method as claimed in claim 15, wherein the device selected from the group consisting of pipes, heat exchangers and computer chips.

30. The method of preparing a device comprising incorporating the composition of claim 1 into polymers which are used to form the device.

31. The method of preparing a device comprising impregnating the composition of claim 1 into the device.

32. The composition of claim 32, wherein the composition is effective against biofilms produced by bacterial species selected from the group consisting of Staphylococcus epidermidis, Enterococcus faecalis, E. coli, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus viridans, Klebsiella oxytoca, Staphylococcus saprophyticus, Providentia stuartii and Serratia marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus epidermidis.

33. The composition of claim 32, wherein the composition is effective against biofilms produced by bacterial species selected from the group consisting of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus epidermidis.

34. The composition of claim 58, wherein the composition is effective against biofilms produced by Staphylococcus epidermidis.