Process for providing antimicrobial surfaces

• US 20070077348A1
• Filed: 10/03/2005
• Published: 04/05/2007
• Est. Priority Date: 10/03/2005
• Status: Active Grant

• Current Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Original Assignee: E. I. du Pont de Nemours and Company (Corteva, Inc.)
• Inventors: Lu, Helen, Chapman, John, Anderson, Albert
• Granted Patent: US 7,601,361 B2
• Time in Patent Office: Days
• US Class Current: 427/2.260
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 29/048 Other specific proteins or polypeptides not covered by A61L29/045 - A61L29/047
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C09D 5/14 Paints containing biocides, e.g. fungicides, insecticides or pesticides C09D5/16 takes precedence

Abstract

Processes for providing durable antimicrobial surfaces are disclosed that comprise treating a polymer substrate surface with formaldehyde followed by treatment with an antimicrobial peptide. Further embodiments include articles, including medical devices, characterized by a durable antimicrobial surface provided by the processes of the invention.

Claims

1. A process for providing a durable antimicrobial surface on a polymer substrate comprising:

a) treating a polymer substrate with a first fluid comprising formaldehyde and a co-reactant selected from the group;

acid, anhydride, reactive halide, or mixtures thereof;

wherein the formaldehyde and co-reactant are present in amounts effective to provide a polymer substrate with a chemically modified surface; and

b) treating the chemically modified surface of step (a) with an antimicrobial fluid comprising an effective amount of an antimicrobial peptide sufficient to provide a durable antimicrobial surface.

3. The process of claims 1 or 2, wherein the antimicrobial fluid further comprises an effective amount of base catalyst.

4. The process of claims 1 or 2 wherein the antimicrobial fluid further comprises a base catalyst selected from the group:

potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, trimethylamine, triethylamine, tripropylamine, diisopropylethylamine and tributyl amine.

5. The process of claims 1 or 2, wherein the polymer substrate of step (a) is comprised of one or more homopolymers, copolymers, block copolymers or graft polymers selected from the group:

polyamide, polyurethane, and polyurea.

6. The process of claims 1 or 2, wherein the polymer substrate of step (a) is a thermoplastic polyurethane elastomer.

7. The process of claims 1 or 2, wherein said antimicrobial peptide is characterized by a weight average molecular weight of about 1000 to about 60,000 Daltons.

8. The process of claims 1 or 2, wherein said antimicrobial peptide is one or more linear cationic peptide(s).

9. The process of claims 1 or 2, wherein the durable antimicrobial surface is provided on a medical device.

10. The process of claims 1 or 2, wherein said formaldehyde is selected from the group:

aqueous formaldehyde, paraformaldehyde and trioxane.

11. The process of claim 1 wherein the co-reactant of step (a) is selected from the group:

trimethylsilylchloride, trimethylsilylbromide, and hydrogen chloride.

13. The process of claim 1, wherein said first fluid consists essentially of paraformaldehyde and trimethylsilylchloride.

14. The process of claims 1 or 2, wherein treating the chemically modified surface with said antimicrobial fluid is performed at a reaction temperature of about 4°

C. to about 100°

C., for a reaction time of about 0.1 to about 10 hours.

16. The process of claims 1 or 2, wherein the antimicrobial peptide is characterized by a weight average molecular weight of about 1,000 to about 60,000 Daltons and contains a net positive charge of greater than 1 at physiological pH.

17. The process of claims 1 or 2, wherein the antimicrobial peptide is selected from the group consisting of linear cationic α

-helical peptides of 8 to 40 amino acid residues.

18. The process of claims 1 or 2, wherein the antimicrobial peptide is selected from the group:

19. The process of claims 1 or 2, wherein the polymer substrate is a nonwoven fabric.

20. The process of claims 1 or 2, wherein the polymer substrate is a fiber.

21. The process of claims 1 or 2, wherein the polymer substrate is a film.

22. The process of claim 1 or 2, wherein the polymer substrate is selected from the group:

catheters, pacemaker leads, vascular grafts, blood tubing, balloons, shunts, cardiac-assist devices, and urological implants; and

barrier materials selected from the group;

wound dressings, surgical gowns, gloves, aprons, and drapes.

23. An article selected from the group consisting of a non-woven fabric, fiber, film, catheters, pacemaker leads, vascular grafts, blood tubing, balloons, shunts, cardiac-assist devices, and urological implants;

and barrier materials selected from the group;

wound dressings, surgical gowns, gloves, aprons, and drapes, characterized by a durable antimicrobial surface provided by the process of claims 1 or 2.

24. A medical device characterized by a durable antimicrobial polymeric surface provided by the process of claims 1 or 2.

25. The process of claims 1 or 2, further comprising washing said durable antimicrobial surface with one or more wash solvents to remove excess antimicrobial peptide, base if used, and any byproducts;

to provide a durable antimicrobial surface substantially free of non-bonded contaminants.

2. A process for providing a durable antimicrobial surface on a polymer substrate comprising:

a) (1) treating a polymer substrate with a first alternative fluid comprising formaldehyde and a hydroxymethylation catalyst wherein the formaldehyde and hydroxymethylation catalyst are present in an amount effective to provide a polymer substrate with a hydroxymethyl surface;

(2) treating the hydroxymethyl surface with a second alternative fluid comprising a reactant selected from the group;

acid, anhydride, reactive halide, and mixtures thereof;

in an amount effective to provide a polymer substrate with a chemically modified surface; and

b) treating the chemically modified surface of step (a) (2), with an antimicrobial fluid comprising an effective amount of an antimicrobial peptide sufficient to provide a durable antimicrobial surface.

12. The process of claim 2 wherein the reactant of step (a) (2) is selected from the group:

trimethylsilylchloride, trimethylsilylbromide, and hydrogen chloride.

15. The process of claim 2, wherein said hydroxymethylation catalyst is selected from the group:

hydrogen chloride, sulfuric acid, glacial acetic acid formic acid, sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate.