Antimicrobial polymer

• US 6,939,554 B2
• Filed: 02/05/2002
• Issued: 09/06/2005
• Est. Priority Date: 02/05/2002
• Status: Expired due to Fees

• Current Assignee: The Michigan Biotechnology Institute
• Original Assignee: The Michigan Biotechnology Institute
• Inventors: Wright, Stacy C., Huang, Zhi-Heng, McDonald, William F.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): CHANNAVAJJALA, LAKSHMI SARADA
• Application Number:
  US10/068,054
• Publication Number:
  US 20030157193A1
• Time in Patent Office: 1,309 Days
• Field of Search: 424/405, 424/78.08, 424/78.18, 424/78.31, 424/78.35, 514/772, 528/332
• US Class Current: 424/405
• 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 the group consisting of 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;

wherein the polymer is a polyamide, and the polymer is synthesized by (i) reacting a monomer selected from the group consisting of 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 the group consisting of RNH₂, RR₁NH, polyalkylene polyamines, and mixtures thereof, and (ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from the group consisting of R₂NH₂, R₂ R₃NH, polyalkylene polyamines, and mixtures thereof, wherein R, R₁, 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 or combinations thereof; and

at least one of the selected amines includes at least two amino groups.

2. The polymeric composition of claim 1 wherein R and R₁ are alkyl.

3. The composition of claim 2 wherein the second amine is a polyalkylene polyamine.

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

5. The composition of claim 1, wherein the monomer is selected from the group consisting of 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 the group consisting of maleic anhydride, maleic acid esters, and mixtures thereof.

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

8. 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.

9. The composition of claim 8, wherein the crosslinking agent comprises tris(hydroxymethyl)phosphine.

10. The composition of claim 1 wherein the antimicrobial agent comprises chlorhexidine and dimethylchlorophenol.

11. The composition of claim 1 wherein the antimicrobial agent comprises dimethylchlorophenol.

12. The composition of claim 1, wherein the antimicrobial agent comprises triclosan.

13. The composition of claim 1 wherein the antimicrobial agent comprises thymol.

14. The composition of claim 1 wherein the antimicrobial agent comprises cetyl pyridinium chloride.

15. The composition of claim 1 wherein the antimicrobial agent comprises gentian violet, dimethyl gentian violet, or a mixture thereof.

16. The composition of claim 1 wherein the antimicrobial agent comprises chlorhexidine.

17. The composition of claim 1 wherein the antimicrobial agent comprises iodine, an iodine complex, or a mixture thereof.

38. The polymeric composition of claim 1 wherein the crosslinking agent is selected from the group consisting of aliphatic isocyanate compounds having 2 or more —

N═

C═

O groups;

aromatic isocyanate compounds having 2 or more —

N═

C═

O groups;

aromatic aldehyde compounds having 2 or more —

CHO groups;

phosphines having the general formula (A)₂P(B) wherein A is hydroxyalkyl, and B is hydroxyalkyl, alkyl, or aryl;

epoxy resins having end groups of the formula;

and mixtures thereof.

39. The polymeric composition of claim 1, wherein the crosslinking agent comprises gluteraldehyde and tris(hydroxymethyl)phosphine.

18. 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;

wherein the polymer is a polyamide, and the polyamide is synthesized by;

(i) reacting a monomer selected from the group consisting of 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 the group consisting of RNH₂, RR₁NH, polyalkylene polyamines and mixtures thereof, and

(ii) reacting the intermediate reaction product and a second amine to form the polyamide, wherein the second amine is selected from the group consisting of R₂NH₂, R₂R₃NH, polyalkylene polyamines and mixtures thereof, wherein R, R₁, 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 or combinations thereof; and

at least one of the selected amines includes at least two amino groups;

(b) mixing the polymer with a crosslinking agent and an antimicrobial agent selected from the group consisting of 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.

19. The process of claim 18 wherein the crosslinking agent selected from the group consisting of polyaldehydes, phosphines having the general formula (A)₃P, wherein A is hydroxyalkyl, and mixtures thereof.

20. The process of claim 18 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.

21. The process of claim 18 wherein the substrate comprises a polymeric material selected from the group consisting of 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.

22. The process of claim 18 wherein the antimicrobial agent is selected from the group consisting of cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.

23. The process of claim 18 wherein R and R₁ are alkyl.

24. The process of claim 23 wherein the second amine is a polyalkylene polyamine.

25. The process of claim 18, wherein the monomer is selected from the group consisting of maleic anhydride, maleic acid esters, and mixtures thereof.

26. The process of claim 24, wherein the first amine comprises tetradecylamine and the polyalkylene polyamine comprises pentaethylenehexamine.

40. The process of claim 18, wherein the crosslinking agent is selected from the group consisting of aliphatic isocyanate compounds having 2 or more —

N═

C═

O groups;

aromatic isocyanate compounds having 2 or more —

N═

C═

O groups;

aromatic aldehyde compounds having 2 or more —

CHO groups;

phosphines having the general formula (A)₂P(B) wherein A is hydroxyalkyl, and B is hydroxyalkyl, alkyl, or aryl;

epoxy resins having end groups of the formula;

and mixtures thereof.

41. The process of claim 18, wherein the monomer is selected from the group consisting of unsaturated dicarboxylic acids, esters of unsaturated dicarboxylic acids, anhydrides of unsaturated dicarboxylic acids, and mixtures thereof.

42. The process of claim 18, wherein the monomer is selected from the group consisting of maleic anhydride, maleic acid esters, and mixtures thereof.

43. The process of claim 18, wherein the crosslinking agent comprises gluteraldehyde and tris(hydroxymethyl)phosphine.

27. A polyamide material formed from:

(A) a polyamide formed from a mixture which comprises;

one or more monomers selected from the group consisting of unsaturated carboxylic acids, esters of unsaturated carboxylic acids, anhydrides of unsaturated carboxylic acids, and mixtures thereof, and one or more amines selected from the group consisting of polyalkylene polyamines and amines having the formula RNH₂ or RR₁NH, wherein R and R₁ contain between 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfer, phosphorus, and combinations thereof, and wherein at least one of the selected amines includes at least two amino groups; and

(B) an antimicrobial agent comprising an agent selected from the group consisting of quaternary ammonium compounds, gentian violet compounds, substituted or unsubstituted phenols, biguanide compounds, iodine compounds, and mixtures thereof;

(C) a crosslinking agent containing at least two functional groups capable of reacting with amino groups.

28. The polyamide material of claim 27, wherein the crosslinking agent comprises a phosphine having the general formula (A)₃P, wherein A is hydroxyalkyl.

29. The polyamide material of claim 28, wherein the crosslinking agent comprises tris(hydroxymethyl)phosphine.

30. A The polyamide material of claim 27, wherein the crosslinking agent comprises gluteraldehyde and tris(hydroxymethyl)phosphine.

31. The polyamide material of claim 27, wherein the crosslinking agent comprises an agent selected from the group consisting of aliphatic isocyanate compounds having 2 or more —

N═

C═

O groups;

aromatic isocyanate compounds having 2 or more —

N═

C═

O groups;

aromatic aldehyde compounds having 2 or more —

CHO groups;

phosphines having the general formula (A)₂P(B) wherein A is hydroxyalkyl, and B is hydroxyalkyl, alkyl, or aryl;

epoxy resins having end groups of the formula;

and mixtures thereof.

32. The polyamide material of claim 27, wherein the antimicrobial agent comprises an agent selected from the group consisting of cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.

33. The polyamide material of claim 27, wherein the one or more monomers are selected from the group consisting of maleic anhydride, maleic acid esters, and mixtures thereof.

34. The polyamide material of claim 27, wherein the one or more monomers are selected from the group consisting of unsaturated dicarboxylic acids, esters of unsaturated dicarboxylic acids, and anhydrides of unsaturated dicarboxylic acids and mixtures thereof.

35. The polyamide material of claim 27, wherein the one or more amines comprise tetradecylamine.

36. The polyamide material of claim 27, wherein the one or more amines comprise pentaethylenehexamine.

37. The polyamide material of claim 27, wherein the one or more amines comprise polyalkylene polyamine and an amine having the formula RNH₂, wherein R is alkyl.

44. A polymeric material comprising:

(A) a polymer formed by a process comprising;

reacting a reaction mixture comprising a monomer selected from the group consisting of unsaturated carboxylic acids, esters of unsaturated carboxylic acids, anhydrides of unsaturated carboxylic acids, and mixtures thereof; and

one or more amines selected from polyalkylene polyamines and amines having the formula RNH₂ or RR₁NH, wherein R and R₁ contain between 1 and 50 carbon atoms and are optionally substituted with heteroatoms oxygen, nitrogen, sulfur, phosphorus, and combinations thereof, wherein the selected amine includes at least one amine having at least two amino groups; and

(B) an antimicrobial agent comprising an agent selected from the group consisting of quaternary ammonium compounds, gentian violet compounds, substituted or unsubstituted phenols, biguanide compounds, iodine compounds, and mixtures thereof.

45. The polymeric material of claim 44, wherein the monomer is selected from the group consisting of unsaturated dicarboxylic acids, esters of unsaturated dicarboxylic acids, anhydrides of unsaturated dicarboxylic acids, and mixtures thereof.

46. The polymeric material of claim 45, wherein the monomer is selected from the group consisting of maleic anhydride, maleic acid esters, and mixtures thereof.

47. The polymeric material of claim 46, wherein the antimicrobial agent is selected from the group consisting of cetyl pyridinium chloride, gentian violet, dimethyl gentian violet, dimethylchlorophenol, triclosan, thymol, chlorhexidine, iodine, and mixtures thereof.

48. The polymeric material of claim 44, wherein R and R₁ are alkyl.

49. The polymeric material of claim 44, wherein one or more selected amines comprises a polyalkylene polyamine.

50. The polymeric material of claim 44, wherein RNH₂ comprises tetradecylamine and the polyalkylene polyamine comprises pentaethylenehexamine.

51. The polyamide material of claim 44, wherein the one or more amines comprise polyalkylene polyamine and an amine having the formula RNH₂, wherein R is alkyl.