Bio-film resistant surfaces

• US 9,981,069 B2
• Filed: 12/09/2014
• Issued: 05/29/2018
• Est. Priority Date: 06/20/2007
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Modak, Shanta, Ghosh, Arnab Kumar, Citron, Ronald, Dongre, Santoshkumar Hanmantrao, Baiju, Nayana
• Primary Examiner(s): PACKARD, BENJAMIN J
• Application Number:
  US14/564,920
• Publication Number:
  US 20150118275A1
• Time in Patent Office: 1,267 Days
• CPC Class Codes: A01N 25/10 Macromolecular compounds
• CPC Class Codes: A01N 31/02 Acyclic compounds
• CPC Class Codes: A01N 37/36 containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
• CPC Class Codes: A01N 47/44 Guanidine; Derivatives thereof
• CPC Class Codes: A01N 59/16 Heavy metals; Compounds thereof
• CPC Class Codes: A61L 15/46 Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 26/0052 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence

Abstract

The present invention relates to methods and compositions for rendering a surface resistant to bio-film formation by a combination of an alkanediol and an antimicrobial agent (and, optionally, an organic hydroxy acid). The invention provides for compositions which may be used to render surfaces bio-film resistant, articles having bio-film resistant surfaces, and methods for their preparation. The present invention may be advantageously applied to medical articles as well as articles used in non-medical contexts, such as child care or food preparation.

Claims

1. A composition for preparing a bio-film resistant surface comprising

(a) one or more antimicrobial agent present at a concentration of between about 0.05 and 5.0% weight/volume (w/v);

(b) one or more releasing agent present at a concentration of between about 0.05 and 5.0% w/v; and

(c) a lubricious biomedical polymeric matrix comprising

(i) one or more biomedical polymer present at a concentration of between about 0.2 and 30% w/v;

(ii) decanediol present at a concentration of between about 0.01 and 5.0% w/v; and

(iii) one or more solvent present at a concentration of between about 10 and 70% volume/volume (v/v).

2. The composition of claim 1, wherein the one or more antimicrobial agent is selected from the group consisting of biguanide, chlorinated phenol, silver salt, quaternary ammonium compound, povidone iodine, nitrofurazone, berberine, alkanediol, and combinations thereof.

3. The composition of claim 2, wherein the biguanide is selected from the group consisting of chlorhexidine base, chlorhexidine salt, a combination of chlorhexidine salt and base, polyhexanide, alexidine, and combinations thereof.

4. The composition of claim 2, wherein the chlorinated phenol is selected from the group consisting of triclosan, 4-chloro-3,5-dimethylphenol (PCMX), and combinations thereof.

5. The composition of claim 2, wherein the quaternary ammonium compound is selected from the group consisting of benzalkonium chloride, benzethonium chloride, and combinations thereof.

6. The composition of claim 1, wherein the one or more antimicrobial agent comprises chlorhexidine base, chlorhexidine salt, or a combination of chlorhexidine salt and base;

and a silver salt.

7. The composition of claim 1, wherein the one or more releasing agent is selected from the group consisting of citric acid, lactic acid, glycolic acid, mandelic acid, benzoic acid, salicylic acid, acetyl salicylic acid, ascorbic acid, and combinations thereof.

8. The composition of claim 1, wherein the one or more biomedical polymer is selected from the group consisting of polyurethane, aliphatic polyether-based polyurethane, silicone polymer, silicone adhesive, hydrophilic cellulose polymer, hydrophobic cellulose polymer, hydrophilic-hydrophobic polymer, hydroxypropyl methyl-cellulose stearoxy ether, biodegradable polymer, polylactic acid, polyglycolic acid, and combinations thereof.

9. The composition of claim 8, wherein the one or more biomedical polymer comprises polyurethane and silicone adhesive.

10. The composition of claim 1, wherein

(a) the one or more antimicrobial agent comprises chlorhexidine base and is present at a concentration of between about 0.5 and 5.0% w/v;

(b) the one or more releasing agent is present at a concentration of between about 0.2 and 5.0% w/v and is selected from the group consisting of lactic acid, mandelic acid, and combinations thereof; and

(c) the lubricious biomedical polymeric matrix comprises

(i) polyurethane biomedical polymer present at a concentration of between about 1 and 20% w/v and silicone adhesive biomedical polymer present at a concentration of between about 1 and 10% w/v;

(ii) decanediol present at a concentration of between about 0.01 and 5.0% w/v; and

(iii) solvent comprising methanol present at a concentration of between about 10 and 50% v/v and tetrahydrofuran present at a concentration of between about 20 and 70% v/v.

11. A composition for preparing a lubricious surface comprising

(a) one or more biomedical polymer present at a concentration of between about 0.2 and 30% w/v selected from the group consisting of hydrophilic polyurethane polymer, hydrophobic silicone polymer, and combinations thereof;

(b) decanediol present at a concentration of between about 0.01 and 5.0% w/v; and

(c) one or more solvent present at a concentration of between about 10 and 70% volume/volume (v/v).

12. The composition of claim 11, wherein the one or more solvent comprises methanol present at a concentration of between about 10 and 50% v/v and tetrahydrofuran present at a concentration of between about 20 and 70% v/v.

13. The composition of claim 12, wherein the hydrophilic polyurethane polymer is at a concentration of between about 0.5 and 10.0% w/v when present and the hydrophobic silicone polymer is at a concentration of between about 1 and 10% w/v when present.

14. A method of producing a bio-film resistant surface, comprising exposing the surface to a composition for preparing a bio-film resistant surface comprising

(a) one or more antimicrobial agent present at a concentration of between about 0.05 and 7.0% w/v;

(b) one or more releasing agent present at a concentration of between about 0.05 and 5.0% w/v; and

(c) a lubricious biomedical polymeric matrix comprising

(i) one or more biomedical polymer present at a concentration of between about 0.2 and 30% w/v;

(ii) decanediol present at a concentration of between about 0.01 and 5.0% w/v; and

(iii) one or more solvent present at a concentration of between about 10 and 70% volume/volume (v/v).

15. A method of rendering a surface of a medical article resistant to bio-film formation, comprising

(a) exposing the surface to a first composition comprising

(i) one or more urethane adhesive present at a concentration of between about 5 and 50% w/v;

(ii) one or more silicone adhesive present at a concentration of between about 1 and 10% w/v;

(iii) one or more solvent;

(b) allowing the first solution to dry; and

(c) exposing the surface to a second composition comprising

(i) one or more antimicrobial agent present at a concentration of between about 0.05 and 7.0% w/v;

(ii) one or more releasing agent present at a concentration of between about 0.05 and 5.0% w/v; and

(iii) a lubricious biomedical polymeric matrix comprising

(1) one or more biomedical polymer present at a concentration of between about 0.2 and 30% w/v;

(2) decanediol present at a concentration of between about 0.01 and 5.0% w/v; and

(3) one or more solvent present at a concentration of between about 10 and 70% volume/volume (v/v).

16. The method of claim 15, wherein the first composition further comprises decanediol present at a concentration of between about 0.01 and 5.0% w/v.

17. The method of claim 15, wherein the second composition comprises

(i) chlorhexidine base as the antimicrobial agent;

(ii) lactic acid, mandelic acid, or combinations thereof, as the one or more releasing agent; and

(iii) wherein the lubricious biomedical polymeric matrix comprises

(1) polyurethane biomedical polymer present at a concentration of between about 1 and 20% w/v and silicone adhesive biomedical polymer present at a concentration of between about 1 and 10% w/v;

(ii) decanediol present at a concentration of between about 0.01 and 5.0% w/v; and

(iii) solvent comprising methanol present at a concentration of between about 10 and 50% v/v and tetrahydrofuran present at a concentration of between about 20 and 70% v/v.

18. A method of producing a bio-film resistant inner surface of a device comprising exposing an inner surface to a composition comprising

(a) one or more antimicrobial present at a concentration of between about 0.05 and 7.0% w/v selected from the group consisting of chlorhexidine base, chlorhexidine acetate, and a combination of chlorhexidine base and chlorhexidine acetate;

and

(b) one or more solvent present at a concentration of between about 2 and 20% v/v selected from the group consisting of methyl-ethyl-ketone, methanol, ethanol, isopropanol, acetone, tetrahydrofuran, and combinations thereof,

wherein the inner surface is exposed to the composition for a time sufficient to impregnate the inner surface with an antimicrobially effective amount of the composition.

19. The method of claim 18, wherein the antimicrobial comprises chlorhexidine base at a concentration of between about 0.1 and 5.0% w/v, and wherein the composition further comprises a fruit acid present at a concentration between about 0.1 and 5.0% w/v selected from the group consisting of lactic acid, mandelic acid, and combinations thereof.

20. The method of claim 18, further comprising exposing an outer surface of the device to a composition comprising

(a) one or more antimicrobial agent present at a concentration of between about 0.05 and 7.0% weight/volume (w/v);

(b) one or more releasing agent present at a concentration of between about 0.05 and 5.0% w/v; and

(c) a lubricious biomedical polymeric matrix comprising

(i) one or more biomedical polymer present at a concentration of between about 0.2 and 30% w/v;

(ii) decanediol present at a concentration of between about 0.01 and 5.0% w/v; and

(iii) one or more solvent present at a concentration of between about 10 and 70% volume/volume (v/v).

21. A medical device prepared according to the method of any one of claims 14, 15, and 18.

22. The composition of claim 1, wherein the surface is a catheter surface.

23. The composition of claim 11, wherein the surface is a catheter surface.