Systems and methods that kill infectious agents (bacteria) without the use of a systemic anti-biotic

• US 20110200655A1
• Filed: 02/16/2011
• Published: 08/18/2011
• Est. Priority Date: 02/16/2010
• Status: Abandoned Application

• Current Assignee: Anita Margarette Chambers, Michael Darryl Black
• Original Assignee: Anita Margarette Chambers, Michael Darryl Black
• Inventors: Black, Michael Darryl, Chambers, Anita Margarette
• Application Number:
  US13/028,460
• Publication Number:
  US 20110200655A1
• Time in Patent Office: Days
• US Class Current: 424/404
• 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 25/10 Macromolecular compounds
• CPC Class Codes: A01N 25/34 Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
• CPC Class Codes: A01N 33/12 Quaternary ammonium compounds
• CPC Class Codes: A01N 37/52 containing groups, e.g. carboxylic acid amidines
• CPC Class Codes: A01N 43/40 six-membered rings
• CPC Class Codes: A01N 43/90 having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
• CPC Class Codes: A01N 47/44 Guanidine; Derivatives thereof
• CPC Class Codes: A01N 55/00 Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur containing organo-phosphorus compounds A01N57/00
• CPC Class Codes: A61L 15/44 Medicaments
• 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 2300/606 Coatings
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A medical product is provided that is selected from at least one of, nasal cannulas, oxygen masks, wound dressings, bandages, band aids, catheters, endotrachial tubes, condoms, surgical and other gloves, sheaths for endoscopy probes, and medical products that physically touch the body. A coating is included with at least one of, a non-antibiotic, antimicrobial and/or antiviral substance that prevents further local, non-systemic, colonization of infections.

Claims

1. A medical product, comprising:

a medical product selected from the group of, nasal cannulas, oxygen masks, wound dressings, bandages, band aids, catheters, endotrachial tubes, condoms, surgical and other gloves, sheaths for endoscopy probes, and medical products that physically touch the body; and

a coating that includes at least one of, a non-antibiotic, antimicrobial and/or antiviral substance that prevents further local, non-systemic, colonization of infections.

2. The product of claim 1, wherein the infection is including but not limited to Methacillin-Resistant Staphylococcus Auereus (MRSA).

3. The product of claim 1, wherein the coating is an intrinsically antimicrobial material that includes:

an absorbent polymeric matrix having an enhanced surface area;

wherein the enhanced surface area further comprises a polymer of antimicrobial monomeric moieties attached to the matrix via non-siloxane covalent chemical bonds so as to result in a structure which is less prone to degradation by acids or bases produced during bacterial growth and consequent detachment of the polymer of antimicrobial monomeric moieties from the matrix, whereby the material remains antimicrobial after exposure of the material to skin or aqueous biological fluids.

4. The product of claim 3, wherein the aqueous biological fluids are bodily fluids, sweat, tears, mucus, urine, menses, blood, wound exudates, or mixtures thereof.

5. The product of claim 3, wherein molecules of the polymer are attached to the matrix via one or more covalent carbon-oxygen-carbon bonds, or carbon-carbon bonds, or carbon-nitrogen bonds, or combinations thereof.

6. The product of claim 3, wherein the antimicrobial monomeric moieties are allyl- or vinyl-containing monomers.

7. The product of claim 3, wherein the antimicrobial monomeric moieties comprise at least one quaternary ammonium compound.

8. The product of claim 4, wherein the quaternary ammonium compound is dimethyldiallyl ammonium chloride, or a trialkyl(p-vinylbenzyl)ammonium chloride, or a p-trialkylaminoethyl styrene monomer.

9. The product of claim 3, wherein the matrix comprises cellulose.

10. The product of claim 3, wherein the matrix comprises a polyethylene oxide, a polyvinyl alcohol, or a polyacrylate.

11. The product of claim 3, wherein the matrix consists essentially of hydrophilic fibers or filaments having a superabsorbent capacity for aqueous biological fluids as evidenced by being capable of absorbing at least about thirty times its own weight of water.

12. A medical product, comprising:

a medical product selected from the group of, nasal cannulas, oxygen masks, wound dressings, bandages, band aids, catheters, endotrachial tubes, condoms, surgical and other gloves, sheaths for endoscopy probes, and medical products that physically touch the body; and

a coating including a polymer having the formula R(LE)_x wherein R is a polymeric core having a number average molecular weight of from 5000 to 7,000,000 daltons and having x endgroups, x being an integer .gtoreq.1, E is an endgroup covalently linked to polymeric core R by linkage L, L is a divalent oligomeric chain, having at least 5 identical repeat units, capable of self-assembly with L chains on adjacent molecules of the polymer, and the moieties (LE)_x in the polymer may be the same as or different from one another, wherein E is at least one of a non-antibiotic, antimicrobial and/or antiviral agent.

13. The product of claim 12, wherein all of the moieties (LE_x in the polymer are the same as one another.

14. The product of claim 12, wherein L comprises a divalent alkane, polyol, polyamine, polysiloxane, or fluorocarbon of from 8 to 24 units in length.

15. The product of claim 12, wherein E is an endgroup that is positively charged, negatively charged, or that contains both positively charged and negatively charged moieties.

16. The product of claim 12, wherein E is an endgroup that is hydrophilic, hydrophobic, or that contains both hydrophilic and hydrophobic moieties.

17. The product of claim 12, wherein E is a biologically active endgroup, such as heparin.

18. The product of claim 17, wherein E is heparin binding endgroup such as PDAMA or the like that is linked to the polymer backbone via a self assembling polyalkylene spacer of different chain lengths, typically between 8 and 24 units.

19. The product of claim 12, the antimicrobial moiety is selected from at least one of, a quaternary ammonium molecule, and an oligermeric compounds including but not limited to a poly quat derivatized from an ethylenically unsaturated diamine and an ethylenically unsaturated dihalo compound.

20. The product of claim 19, wherein the antimicrobial moiety is an organic biocidal compound that prevents the formation of a biological microorganism, and has fungicidal, algicidal, or bactericidal activity and low toxicity to humans and animals, e.g., a quaternary ammonium salt that bears additional reactive functional group capable of attaching to the polymer main chain, such as compounds having the following formula:

wherein R₁, R₂, and R₃ are radicals of straight or branched or cyclic alkyl groups having one to eighteen carbon atoms or aryl groups and R₄ is an amino-, hydroxyl-, isocyanato-, vinyl-, carboxyl-, or other reactive group-terminated alkyl chain capable of covalently bonding to the base polymer, wherein, due to the permanent nature of the immobilized organic biocide, the polymer thus prepared does not release low molecular weight biocide to the environment and has long lasting antimicrobial activity.

21. The product of claim 12, wherein E is an amino group, an isocyanate group, a hydroxyl group, a carboxyl group, a carboxaldehyde group, or an alkoxycarbonyl group.

22. The product of claim 21, wherein E is a protected amino group linked to the polymer backbone via a self assembling polyalkylene spacer of different chain lengths, typically between 8 and 24 units.

23. The product of claim 12, wherein E is selected from the group consisting of hydroxyl, carboxyl, amino, mercapto, azido, vinyl, bromo, acrylate, methacrylate, —

O(CH₂CH₂O)₃H, —

(CH₂CH₂O)₄H, —

O(CH₂CH₂O)₆H, —

O(CH₂CH₂O)₆CH₂COOH, —

O(CH₂CH₂O)₃CH₃, —

(CH₂CmH₂O)4CH₃, —

O(CH₂CH₂O)₆CH₃, trifluoroacetamido, trifluoroacetoxy, 2′

,2′

,2′

-trifluorethoxy, and methyl.

24. The product of claim 12, wherein R has a number average molecular weight of from 100,000 to 1,000,000 daltons.

25. The product of claim 12, wherein R is biodegradable and/or bioresorbable.

26. The product of claim 24, wherein R is a linear base polymer, x is 2, E is a surface active endgroup, and L is a polymethylene chain of the formula —

(CH₂)_n—

wherein n is an integer of from 8 to 24.

27. The product of claim 26, wherein the linear base polymer is a polyurethane and wherein the endgroup is selected from the group consisting of monofunctional aliphatic polyols, aliphatic or aromatic amines, and mixtures thereof.

28. The product of claim 12, wherein the polymer has a molecular weight of up to 5,000,000 daltons.

29. The product of claim 12, wherein at least some of the moieties (LE)_x in the polymer differ from other of the moieties (LE)_x in the polymer.

30. The product of claim 29, wherein the polymer is a polyurethane or polyurea polymer in which about half of the moieties (LE)_x in the polymer have E groups derived from a polyethylene oxide having a molecular weight of about 2000 and the reactive monomer that forms the endgroup has the formula HO(CH₂)₁₇(CH₂CH₂O)₄₅CH₃, and about half of the moieties (LE)_x in the polymer have E groups that are derived from a polyethylene oxide having a molecular weight of about 5000 and the reactive monomer that forms the endgroup has the formula HO(CH₂)₁₇(CH₂CH₂O)₁₁₄—

CH₃.

31. A medical product, comprising:

a medical product selected from the group of, nasal cannulas, oxygen masks, wound dressings, bandages, band aids, catheters, endotrachial tubes, condoms, surgical and other gloves, sheaths for endoscopy probes, and medical products that physically touch the body; and

a material coupled to the medical product, the material including one or more non-hydrolyzable, non-leachable polymer chains covalently bonded by non-siloxane bonds to the substrate;

wherein the non-hydrolyzable, non-leachable polymer chains comprise a multitude of antimicrobial groups attached to the non-hydrolyzable, non-leachable polymer chains by covalent bonds; and

wherein a sufficient number of the non-hydrolyzable, non-leachable polymer chains are covalently bonded to sites of the substrate to render the material antimicrobial, or receptive to avid binding of negatively charged dye molecules, when exposed to aqueous fluids, menses, bodily fluids, skin, cosmetic compositions, or wound exudates, wherein the material has associated therewith a plurality of anionically charged biologically or chemically active compounds.

32. The product of claim 31, wherein the antimicrobial groups comprise at least one quaternary ammonium structure.

33. The product of claim 31, wherein the antimicrobial groups comprise at least one non-ionic structure.

34. The product of claim 33, wherein the at least one non-ionic structure comprises a biguanide.

35. The product of claim 31, wherein the non-hydrolyzable, non-leaching polymer chains have an average degree of polymerization selected from about 5 to 1000, 10 to 500, and 10 to 100.

36. The product of claim 31, wherein the material comprises all or part of a wound dressing, sanitary pad, a tampon, an intrinsically antimicrobial absorbent dressing, a diaper, toilet paper, a sponge, a sanitary wipe, isolation and surgical gowns, gloves, surgical scrubs, sutures, sterile packaging, floor mats, lamp handle covers, burn dressings, gauze rolls, blood transfer tubing or storage container, mattress cover, bedding, sheet, towel, underwear, socks, cotton swabs, applicators, exam table covers, head covers, cast liners, splint, paddings, lab coats, air filters for autos, planes or HVAC systems, military protective garments, face masks, devices for protection against biohazards and biological warfare agents, lumber, meat or fish packaging material, apparel for food handling, paper currency, powder, and other surfaces required to exhibit a non-leaching antimicrobial property and to release over time portions of the biologically or chemically active compound.

37. The product of claim 31, wherein the substrate is comprised, in whole or in part, of cellulose, or other naturally-derived polymers.

38. The product of claim 31 wherein the substrate is comprised, in whole or in part, of synthetic polymers including, but not limited to:

polyethylene, polypropylene, nylon, polyester, polyurethane, or silicone.

39. The product of claim 31, wherein the attachment of the non-hydrolyzable, non-leachable polymer to the substrate is via a carbon-oxygen-carbon bond, also known as an ether linkage, a carbon-carbon bond, and mixtures thereof.

40. The product of claim 39, wherein a cerium-containing catalyst, a peroxide containing catalyst, an Azo catalyst, a redox initiator, a thermolabile or photolabile catalyst catalyzes formation of the ether linkage or the carbon-carbon bond.

41. The product of claim 31 wherein the non-hydrolyzable, non-leachable polymer chains are formed by polymerization of allyl- or vinyl-containing monomers.

42. The product of claim 41 wherein the allyl- or vinyl-monomers are selected from the group consisting of:

styrene derivatives, allyl amines, and ammonium salts.

43. The product of claim 41 wherein the allyl- or vinyl-monomers are selected from the group consisting of:

acrylates, methacrylates, acrylamides, and methacrylamides.

44. The product of claim 43 wherein the or vinyl-containing monomers are selected from the group consisting of:

compounds of the structure CH₂.dbd.CR—

(C.dbd.O)—

X—

(CH₂)_n—

N+R′

R″

R′

″

—

//Y⁻

;

wherein, R is hydrogen or methyl, n equals 2 or 3, X is either O, S, or NH. R′

, R″

, and R′

″

are independently selected from the group consisting of H, C1 to C16 alkyl, aryl, arylamine, alkaryl, and aralkyl, and Y−

is an acceptable anionic counterion to the positive charge of the quaternary nitrogen;

diallyldimethylammonium salts;

vinyl pyridine and salts thereof; and

vinylbenzyltrimethylammonium salts.

45. The product of claim 44 where the allyl- or vinyl-containing monomers are selected from the group consisting of:

dimethylaminoethyl methacrylate;

methyl chloride quaternary; and

dimethylaminoethyl methacrylate;

benzyl chloride quaternary.

46. The product of claim 36 wherein the powder is mica.

47. A medical product, comprising:

a medical product selected from the group of, nasal cannulas, oxygen masks, wound dressings, bandages, band aids, catheters, endotrachial tubes, condoms, surgical and other gloves, sheaths for endoscopy probes, and medical products that physically touch the body; and

a superabsorbent material for absorbing biological fluids coupled to the medical product, the superabsorbent material including one or more non-hydrolyzable, non-leachable polymer chains covalently bonded by non-siloxane bonds to the substrate;

wherein the non-hydrolyzable, non-leachable polymer chains comprise a multitude of antimicrobial groups attached to the non-hydrolyzable, non-leachable polymer chains by covalent bonds; and

wherein a sufficient number of the non-hydrolyzable, non-leachable polymer chains are covalently bonded to sites of the flexible substrate to render the material antimicrobial when exposed to aqueous fluids, menses, bodily fluids, or wound exudates;

wherein the superabsorbent material is capable of absorbing about 30 or more times its own weight of water or other fluids in a single instance; and

wherein the absorbing capacity is the result of branching or crosslinking of the non-hydrolyzable, non-leachable polymer chains, wherein the material has associated therewith a plurality of anionically charged biologically or chemically active compounds.

48. The product of claim 47, wherein the antimicrobial groups comprise at least one quaternary ammonium structure.

49. The product of claim 47, wherein the antimicrobial groups comprise at least one non-ionic structure.

50. The product of claim 49, wherein the at least one non-ionic structure comprises a biguanide.

51. The product of claim 47, wherein the material comprises all or part of a wound dressing, sanitary pad, a tampon, an intrinsically antimicrobial absorbent dressing, a diaper, toilet paper, a sponge, a sanitary wipe, food preparation surfaces, gowns, gloves, surgical scrubs, sutures, needles, sterile packings, floor mats, lamp handle covers, burn dressings, gauze rolls, blood transfer tubing or storage container, mattress cover, bedding, sheet, towel, underwear, socks, cotton swabs, applicators, exam table covers, head covers, cast liners, splint, paddings, lab coats, air filters for autos planes or HVAC systems, military protective garments, face masks, devices for protection against biohazards and biological warfare agents, lumber, meat packaging material, paper currency, powders, and other surfaces required to exhibit a non-leaching antimicrobial or enhanced dye binding properties, and to release over time portions of the biologically or chemically active compound.

52. The product of claim 47, wherein the substrate is comprised, in whole or in part, of cellulose, or other naturally-derived polymers.

53. The product of claim 47 wherein the substrate is comprised, in whole or in part, of synthetic polymers including, but not limited to:

polyethylene, polypropylene, nylon, polyester, polyurethane, or silicone.

54. The product of claim 47, wherein the attachment of the non-hydrolyzable, non-leachable polymer to the substrate is via a carbon-oxygen-carbon bond, also known as an ether linkage, a carbon-carbon bond, or mixtures thereof.

55. The product of claim 54, wherein a cerium-containing catalyst, a peroxide containing catalyst, an Azo catalyst, a thermolabile or photolabile catalyst catalyzes formation of the ether linkage or the carbon-carbon linkage, or mixtures thereof.

56. The product of claim 47 wherein the non-hydrolyzable, non-leachable polymer chains are formed by polymerization of allyl- or vinyl-containing monomers.

57. The product of claim 56 wherein the allyl- or vinyl-monomers are selected from the group consisting of:

styrene derivatives; and

allyl amines or ammonium salts.

58. The product of claim 56 wherein the allyl- or vinyl-monomers are selected from the group consisting of:

acrylates, methacrylates, acrylamides, and methacrylamides.

59. The product of claim 58 wherein the allyl- or vinyl-containing monomers are selected from the group consisting of:

compounds of the structure CH₂.dbd.CR—

(C.dbd.O)—

X—

(CH₂)_n—

N⁺R′

R″

R″

—

//Y⁻

;

wherein, R is hydrogen or methyl, n equals 2 or 3, X is either O, S, or NH, R′

, R″

, and R′

″

are independently selected from the group consisting of H, C1 to C16 alkyl, aryl, arylamine, alkaryl, and aralkyl, and Y−

is an acceptable anionic counterion to the positive charge of the quaternary nitrogen;

diallyldimethylammonium salts;

vinyl pyridine and salts thereof; and

vinylbenzyltrimethylammonium salts.

60. The product of claim 59 where the allyl- or vinyl-containing monomers are selected from the group consisting of:

dimethylaminoethyl methacrylate;

methyl chloride quaternary; and

dimethylaminoethyl methacrylate;

benzyl chloride quaternary.

61. A medical product, comprising:

a medical product selected from the group of, nasal cannulas, oxygen masks, wound dressings, bandages, band aids, catheters, endotrachial tubes, condoms, surgical and other gloves, sheaths for endoscopy probes, and medical products that physically touch the body; and

an antimicrobial composition coupled to the medical product including a plurality of polymeric molecules of variable lengths bearing antimicrobial groups, wherein the polymeric molecules are covalently, non-leachably bound to the substrate, and wherein the coating, layer, or enhanced surface area exhibits antimicrobial activity due to the presence of the antimicrobial groups; and

c. ionically associated biologically or chemically active compounds which are released from the substrate and coating layer over a period of time.

62. The product of claim 61, wherein the antimicrobial groups comprise at least one quaternary ammonium structure.

63. The product of claim 61, wherein the antimicrobial groups comprise at least one non-ionic structure.

64. The product of claim 63, wherein the at least one non-ionic structure comprises a biguanide.

65. The product of claim 61, wherein the material comprises all or part of a wound dressing, sanitary pad, a tampon, an intrinsically antimicrobial absorbent dressing, a diaper, toilet paper, a sponge, a sanitary wipe, food preparation surfaces, gowns, gloves, surgical scrubs, sutures, needles, sterile packings, floor mats, lamp handle covers, burn dressings, gauze rolls, blood transfer tubing or storage container, mattress cover, bedding, sheet, towel, underwear, socks, cotton swabs, applicators, exam table coves, head covers, cast liners, splint, paddings, lab coats, air filters for autos, planes or HVAC systems, military protective garments, face masks, devices for protection against biohazards and biological warfare agents, lumber, meat packaging material, paper currency, powders, and other surfaces required to exhibit a non-leaching antimicrobial or enhanced dye binding properties, and to release over time portions of the biologically or chemically active compound.

66. The product of claim 61, wherein the substrate is comprised, in whole or in part, of cellulose, or other naturally-derived polymers.

67. The product of claim 61 wherein the substrate is comprised, in whole or in part, of synthetic polymers including, but not limited to:

polyethylene, polypropylene, nylon, polyester, polyurethane, or silicone.

68. The product of claim 61, wherein the attachment of the non-hydrolyzable, non-leachable polymer to the substrate is via a carbon-oxygen-carbon bond, also known as an ether linkage, via a carbon-carbon bond, or mixtures thereof.

69. The product of claim 68, wherein a cerium-containing catalyst, a peroxide containing catalyst, an Azo catalyst, a thermolabile or photolabile catalyst catalyzes formation of the ether linkage or the carbon-carbon linkage, or mixtures thereof.

70. The product of claim 61 wherein the non-hydrolyzable, non-leachable polymer chains are formed by polymerization of allyl- or vinyl-containing monomers.

71. The product of claim 70 wherein the allyl- or vinyl-monomers are selected from a group consisting of:

styrene derivatives;

allyl amines and ammonium salts.

72. The product of claim 70 wherein the allyl- or vinyl-monomers are selected from the group consisting of:

acrylates, methacrylates, acrylamides, and methacrylamides.

73. The product of claim 72 wherein the allyl- or vinyl-containing monomers are selected from the group consisting of:

compounds of the structure CH₂.dbd.CR—

(C.dbd.O)—

X—

(CH₂)_n—

N⁺R′

R″

R″

—

//Y⁻

;

wherein, R is hydrogen or methyl, n equals 2 or 3, X is either O, S, or NH, R′

, R″

, and R′

are independently selected from the group consisting of H, C1 to C16 alkyl, aryl, arylamine, alkaryl, and aralkyl, and Y−

is an acceptable anionic counterion to the positive charge of the quaternary nitrogen;

diallyldimethylammonium salts;

vinyl pyridine and salts thereof; and

vinylbenzyltrimethylammonium salts.

74. The product of claim 73 where the allyl- or vinyl-containing monomers are selected from the group consisting of:

dimethylaminoethyl methacrylate;

methyl chloride quaternary; and

dimethylaminoethyl methacrylate;

benzyl chloride quaternary.

75. The product of claim 74, wherein the substrate is selected from the group consisting of:

woven or nonwoven flexible matrices, wherein the composition is formed into the shape of a wound dressing and a powder.

76. The product of claim 74, wherein the coating absorbs aqueous liquids.

77. The product of claim 74, wherein the substrate is wood, lumber, or an extract or a derivative of wood fiber.

78. A medical product, comprising:

a medical product selected from the group of, nasal cannulas, oxygen masks, wound dressings, bandages, band aids, catheters, endotrachial tubes, condoms, surgical and other gloves, sheaths for endoscopy probes, and medical products that physically touch the body; and

an antimicrobial-coated composition coupled to the medical product and including an effective amount of polymeric molecules having a multiplicity of quaternary ammonium groups, wherein the polymeric molecules are non-leachably and covalently bonded to surface sites of the substrate, wherein the polymers do not form using siloxane bonds, and wherein the coating is absorbent of aqueous liquids, and c. associated anionic biologically active or chemically active compound;

whereby the multiplicity of quaternary ammonium groups act to destroy microbes coming in contact with the groups as well as to bind and release the anionic biologically active or chemically active compound.