Antimicrobial polymer

• US 20030157193A1
• Filed: 02/05/2002
• Published: 08/21/2003
• Est. Priority Date: 02/05/2002
• Status: Active Grant

• Current Assignee: The Michigan Biotechnology Institute
• Original Assignee: The Michigan Biotechnology Institute
• Inventors: Huang, Zhi-Heng, McDonald, William F., Wright, Stacy C.
• Granted Patent: US 6,939,554 B2
• Time in Patent Office: Days
• US Class Current: 424/667
• CPC Class Codes: A01N 25/10 Macromolecular compounds
• CPC Class Codes: A01N 31/06 Oxygen or sulfur directly attached to a cycloaliphatic ring system
• CPC Class Codes: A01N 31/14 Ethers
• CPC Class Codes: A01N 33/06 Nitrogen directly attached to an aromatic ring system
• CPC Class Codes: A01N 43/40 six-membered rings
• CPC Class Codes: A01N 47/44 Guanidine; Derivatives thereof
• CPC Class Codes: A01N 59/12 Iodine, e.g. iodophors; Compounds thereof
• CPC Class Codes: A61L 2300/106 Halogens or compounds thereof, e.g. iodine, chlorite
• CPC Class Codes: A61L 2300/202 with halogen atoms, e.g. triclosan, povidone-iodine
• CPC Class Codes: A61L 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/208 Quaternary ammonium compounds
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/442 Colorants, dyes
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C08G 69/02 Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
• CPC Class Codes: C08G 69/48 Polymers modified by chemical after-treatment
• CPC Class Codes: C08K 5/0058 Biocides; macromolecular substances as carriers for biocide material A01N25/10

Abstract

A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from quaternary ammonium compounds, gentian violet compounds, substituted or unsubstituted phenols, biguanide compounds, iodine compounds, and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A)₃P wherein A is hydroxyalkyl; and the antimicrobial agent is chlorhexidine, dimethylchlorophenol, cetyl pyridinium chloride, gentian violet, triclosan, thymol, iodine, and mixtures thereof.

Claims

1. A polymeric composition having antimicrobial properties, the polymeric composition comprising:

a crosslinked chemical combination of (i) a polymer having side chains along a backbone forming the polymer, at least two of the side chains containing an amino group, (ii) an antimicrobial agent selected from quaternary ammonium compounds, gentian violet compounds, substituted or unsubstituted phenols, biguanide compounds, iodine compounds, and mixtures thereof, and (iii) a crosslinking agent containing at least two functional groups capable of reacting with the amino groups.

2. The polymeric composition of claim 1 wherein:

the polymer is a polyamide, and

the polymer is synthesized by (i) reacting a monomer selected from unsaturated carboxylic acids, esters of unsaturated carboxylic acids, anhydrides of unsaturated carboxylic acids, and mixtures thereof, and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR₁NH, RNH₂, RR₁NH₂⁺, RNH₃⁺and mixtures thereof, wherein R and R₁ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, and (ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from R₂R₃NH, R₂NH₂, R₂R₃NH₂⁺, R₂NH₃⁺ and mixtures thereof, wherein R₂ and R₃ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiples of the R, R₁, R₂, and R₃ are in vertically aligned spaced relationship along a backbone formed by the polyamide.

3. The composition of claim 2 wherein R and R₁ are alkyl and the second amine is a polyalkylene polyamine.

4. The composition of claim 3 wherein the first amine is tetradecylamine and the polyalkylene polyamine is pentaethylenehexamine.

5. The composition of claim 2 wherein the monomer is selected from unsaturated dicarboxylic acids, esters of unsaturated dicarboxylic acids, anhydrides of unsaturated dicarboxylic acids, and mixtures thereof.

6. The composition of claim 5 wherein the monomer is selected from maleic anhydride, maleic acid esters, and mixtures thereof.

7. The polymeric composition of claim 2 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.

8. The composition of claim 1 wherein:

the polymer is a polyamide, and

the polymer is synthesized by (i) reacting an α

,β

-unsaturated lactone and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR₁NH, RNH₂, RR₁NH₂⁺, RN H₃⁺ and mixtures thereof, wherein R and R₁ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, and (ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from R₂R₃NH, R₂NH₂, R₂R₃NH₂⁺, R₂NH₃⁺ and mixtures thereof, wherein R₂ and R₃ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiples of the R, R₁, R₂, and R₃ are in vertically aligned spaced relationship along a backbone formed by the polyamide.

9. The composition of claim 8 wherein R and R₁ are alkyl and the second amine is a polyalkylene polyamine.

10. The composition of claim 9 wherein the first amine is tetradecylamine and the polyalkylene polyamine is pentaethylenehexamine.

11. The composition of claim 8 wherein the lactone is 2(5H)-furanone.

12. The composition of claim 8 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.

13. The composition of claim 1 wherein the crosslinking agent is selected from the group consisting of phosphines having the general formula (A)₃P, wherein A is hydroxyalkyl, and mixtures thereof.

14. The composition of claim 13 wherein the crosslinking agent is tris(hydroxymethyl)phosphine.

15. The composition of claim 1 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.

16. The composition of claim 1 wherein the antimicrobial agent includes chlorhexidine and dimethylchlorophenol.

17. The composition of claim 1 wherein the antimicrobial agent is dimethylchlorophenol.

18. The composition of claim 16 wherein the antimicrobial agent is triclosan.

19. The composition of claim 1 wherein the antimicrobial agent is thymol.

20. The composition of claim 1 wherein the antimicrobial agent is cetyl pyridinium chloride.

21. The composition of claim 1 wherein the antimicrobial agent is gentian violet or dimethyl gentian violet.

22. The composition of claim 1 wherein the antimicrobial agent is chlorhexidine.

23. The composition of claim 1 wherein the antimicrobial agent is iodine or an iodine complex.

24. A process for rendering the surface of a substrate antimicrobial, the process comprising:

(a) providing a polymer having side chains along a backbone forming the polymer, at least two of the side chains containing an amino group;

(b) mixing the polymer with a first crosslinking agent, to produce a polymer solution, the first crosslinking agent containing at least two crosslinking functional groups capable of reacting with the amino groups;

(c) coating at least a portion of the substrate with the polymer solution to produce a crosslinked polymer coating on the substrate;

(d) mixing a second crosslinking agent and an antimicrobial agent selected from gentian violet compounds, substituted or unsubstituted phenols, biguanide compounds, and mixtures thereof, to produce a coating solution, the second crosslinking agent containing at least two crosslinking functional groups capable of reacting with the amino groups; and

(e) applying the coating solution to the crosslinked polymer coating on the substrate.

25. The process of claim 24 further comprising:

(f) applying an iodine compound to the crosslinked polymer coating on the substrate after applying the coating solution to the crosslinked polymer coating on the substrate.

26. The process of claim 24 wherein:

the first crosslinking agent is selected from the group consisting of polyaldehydes, phosphines having the general formula (A)₃P, wherein A is hydroxyalkyl, and mixtures thereof, and

the second crosslinking agent is selected from the group consisting of phosphines having the general formula (A)₃P, wherein A is hydroxyalkyl, and mixtures thereof.

27. The process of claim 24 wherein the substrate comprises a polymeric material selected from polyolefins, polyacrylics, polyvinyl chloride, polyamides, polyurethanes, polyurethaneureas, silicone urethane copolymers, polyvinylpyrrolidone, polyvinyl alcohols, cellulosic materials, polystyrene, polyesters, fluorinated polymers, silicone polymers, natural rubber, polycarbonates, and mixtures thereof.

28. The process of claim 24 wherein the antimicrobial agent is selected from gentian violet, dimethyl gentian violet, dimethylchlorophenol, chlorhexidine, and mixtures thereof.

29. The process of claim 24 wherein:

the polymer is a polyamide, and

step (a) comprises;

(i) reacting a monomer selected from unsaturated carboxylic acids, esters of unsaturated carboxylic acids, anhydrides of unsaturated carboxylic acids, and mixtures thereof, and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR₁ NH, RNH₂, RR₁NH₂⁺, RNH₃⁺ and mixtures thereof, wherein R and R₁ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof; and

(ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from R₂R₃NH, R₂NH₂, R₂R₃NH₂⁺, R₂NH₃⁺ and mixtures thereof, wherein R₂ and R₃ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiples of the R, R₁, R₂, and R₃ are in vertically aligned spaced relationship along a backbone formed by the polyamide.

30. The process of claim 29 wherein R and R₁ are alkyl and the second amine is a polyalkylene polyamine.

31. The process of claim 29 wherein the monomer is selected from maleic anhydride, maleic acid esters, and mixtures thereof.

32. The process of claim 29 wherein the antimicrobial agent is selected from gentian violet, dimethyl gentian violet, dimethylchlorophenol, chlorhexidine, and mixtures thereof.

33. The process of claim 24 wherein:

the polymer is a polyamide, and

step (a) comprises;

(i) reacting an α

,β

-unsaturated lactone and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR₁NH, RNH₂, RR₁NH₂⁺, RNH₃⁺ and mixtures thereof, wherein R and R₁ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof; and

(ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from R₂R₃NH, R₂NH₂, R₂R₃NH₂⁺, R₂NH₃⁺ and mixtures thereof, wherein R₂ and R₃ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiples of the R, R₁, R₂, and R₃ are in vertically aligned spaced relationship along a backbone formed by the polyamide.

34. The process of claim 33 wherein R and R₁ are alkyl and the second amine is a polyalkylene polyamine.

35. The process of claim 33 wherein the antimicrobial agent is selected from gentian violet, dimethyl gentian violet, dimethylchlorophenol, chlorhexidine, and mixtures thereof.

36. A process for rendering the surface of a substrate antimicrobial, the process comprising:

(a) providing a polymer having side chains along a backbone forming the polymer, at least two of the side chains containing an amino group;

(b) mixing the polymer with a crosslinking agent to produce a polymer solution, the crosslinking agent containing at least two crosslinking functional groups capable of reacting with the amino groups;

(c) coating at least a portion of the substrate with the polymer solution to produce a crosslinked polymer coating on the substrate;

(d) treating at least a portion of the crosslinked polymer coating with a charge derivatization agent to create a negative charge on the portion of the crosslinked polymer coating; and

(e) applying a cationic antimicrobial agent selected from quaternary ammonium compounds, gentian violet compounds, biguanide compounds, iodine compounds, and mixtures thereof, to the portion of the crosslinked polymer coating.

37. The process of claim 36 wherein:

the crosslinking agent is selected from the group consisting of polyaldehydes, phosphines having the general formula (A)₃P, wherein A is hydroxyalkyl, and mixtures thereof.

38. The process of claim 36 wherein:

the crosslinking agent is selected from the group consisting of phosphines having the general formula (A)₃P, wherein A is hydroxyalkyl, and mixtures thereof.

39. The process of claim 36 wherein the substrate comprises a polymeric material selected from polyolefins, polyacrylics, polyvinyl chloride, polyamides, polyurethanes, polyurethaneureas, silicone urethane copolymers, polyvinylpyrrolidone, polyvinyl alcohols, cellulosic materials, polystyrene, polyesters, fluorinated polymers, silicone polymers, natural rubber, polycarbonates, and mixtures thereof.

40. The process of claim 36 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, chlorhexidine, iodine, and mixtures thereof.

41. The process of claim 36 wherein:

the polymer is a polyamide, and

step (a) comprises;

(i) reacting a monomer selected from unsaturated carboxylic acids, esters of unsaturated carboxylic acids, anhydrides of unsaturated carboxylic acids, and mixtures thereof, and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR₁ NH, RNH₂, RR₁NH₂⁺, RNH₃⁺ and mixtures thereof, wherein R and R₁ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof; and

(ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from R₂R₃NH, R₂NH₂, R₂R₃NH₂⁺, R₂NH₃⁺ and mixtures thereof, wherein R₂ and R₃ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiples of the R, R₁, R₂, and R₃ are in vertically aligned spaced relationship along a backbone formed by the polyamide.

42. The process of claim 41 wherein R and R₁ are alkyl and the second amine is a polyalkylene polyamine.

43. The process of claim 41 wherein the monomer is selected from maleic anhydride, maleic acid esters, and mixtures thereof.

44. The process of claim 41 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, chlorhexidine, iodine, and mixtures thereof.

45. The process of claim 36 wherein:

the polymer is a polyamide, and

step (a) comprises;

(i) reacting an α

,β

-unsaturated lactone and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR₁NH, RNH₂, RR₁NH₂⁺, RNH₃⁺ and mixtures thereof, wherein R and R₁ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof; and

(ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from R₂R₃NH, R₂NH₂, R₂R₃NH₂⁺, R₂NH₃⁺ and mixtures thereof, wherein R₂ and R₃ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiples of the R, R₁, R₂, and R₃ are in vertically aligned spaced relationship along a backbone formed by the polyamide.

46. The process of claim 45 wherein R and R₁ are alkyl and the second amine is a polyalkylene polyamine.

47. The process of claim 45 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, chlorhexidine, iodine, and mixtures thereof.

48. A process for rendering the surface of a substrate antimicrobial, the process comprising:

(a) providing a polymer having side chains along a backbone forming the polymer, at least two of the side chains containing an amino group;

(b) mixing the polymer with a crosslinking agent and an antimicrobial agent selected from quaternary ammonium compounds, gentian violet compounds, substituted or unsubstituted phenols, biguanide compounds, iodine compounds, and mixtures thereof, to produce a polymer solution, the crosslinking agent containing at least two crosslinking functional groups capable of reacting with the amino groups; and

(c) coating at least a portion of the substrate with the polymer solution to produce a crosslinked polymer coating on the substrate.

49. The process of claim 48 wherein:

the crosslinking agent is selected from the group consisting of polyaldehydes, phosphines having the general formula (A)₃P, wherein A is hydroxyalkyl, and mixtures thereof.

50. The process of claim 48 wherein:

the crosslinking agent is selected from the group consisting of phosphines having the general formula (A)₃P, wherein A is hydroxyalkyl, and mixtures thereof.

51. The process of claim 48 wherein the substrate comprises a polymeric material selected from polyolefins, polyacrylics, polyvinyl chloride, polyamides, polyurethanes, polyurethaneureas, silicone urethane copolymers, polyvinylpyrrolidone, polyvinyl alcohols, cellulosic materials, polystyrene, polyesters, fluorinated polymers, silicone polymers, natural rubber, polycarbonates, and mixtures thereof.

52. The process of claim 48 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.

53. The process of claim 48 wherein:

the polymer is a polyamide, and

step (a) comprises;

(i) reacting a monomer selected from unsaturated carboxylic acids, esters of unsaturated carboxylic acids, anhydrides of unsaturated carboxylic acids, and mixtures thereof, and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR₁NH, RNH₂, RR₁NH₂⁺, RNH₃⁺ and mixtures thereof, wherein R and R₁ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof; and

(ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from R₂R₃NH, R₂NH₂, R₂R₃NH₂⁺, R₂NH₃⁺ and mixtures thereof, wherein R₂ and R₃ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiples of the R, R₁, R₂, and R₃ are in vertically aligned spaced relationship along a backbone formed by the polyamide.

54. The process of claim 53 wherein R and R₁ are alkyl and the second amine is a polyalkylene polyamine.

55. The process of claim 53 wherein the monomer is selected from maleic anhydride, maleic acid esters. and mixtures thereof.

56. The process of claim 53 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.

57. The process of claim 48 wherein:

the polymer is a polyamide, and

step (a) comprises;

(i) reacting an α

,β

-unsaturated lactone and a first amine to form an intermediate reaction product, wherein the first amine is selected from RR₁NH, RNH₂, RR₁NH₂⁺, RNH₃⁺ and mixtures thereof, wherein R and R₁ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof; and

(ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from R₂R₃NH, R₂NH₂, R₂R₃NH₂⁺, R₂NH₃⁺ and mixtures thereof, wherein R₂ and R₃ can be the same or different and each contain between about 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, and phosphorus and combinations thereof, wherein multiples of the R, R₁, R₂, and R₃ are in vertically aligned spaced relationship along a backbone formed by the polyamide.

58. The process of claim 57 wherein R and R₁ are alkyl and the second amine is a polyalkylene polyamine.

59. The process of claim 57 wherein the antimicrobial agent is selected from cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.