Polymer compositions with bioactive agent, medical articles, and methods

• US 20050124724A1
• Filed: 12/05/2003
• Published: 06/09/2005
• Est. Priority Date: 12/05/2003
• Status: Active Grant

• Current Assignee: 3M Innovative Properties Company (3M Company)
• Original Assignee: 3M Innovative Properties Company (3M Company)
• Inventors: Rao, Prabhakara S., Ylitalo, Caroline M., Burton, Scott A., Hyde, Patrick D.
• Granted Patent: US 7,745,509 B2
• Time in Patent Office: Days
• US Class Current: 523/122
• CPC Class Codes: A61L 15/18 containing inorganic materials
• CPC Class Codes: A61L 15/22 containing macromolecular materials
• CPC Class Codes: A61L 15/46 Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• CPC Class Codes: A61L 2300/102 Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

A polymer composition that includes a hydrophilic polymer, an optional secondary organic polymer, and a bioactive agent distributed therein, wherein the bioactive agent is selected from the group consisting of a silver compound, a copper compound, a zinc compound, and combinations thereof.

Claims

1. A polymer composition comprising:

a hydrophilic polymer; and

a bioactive agent selected from the group consisting of a metal oxide of silver, copper, zinc, and combinations thereof;

wherein the bioactive agent is dispersed within the hydrophilic polymer; and

wherein substantially all of the bioactive agent has a particle size less than one micron.

2. The polymer composition of claim 1, wherein the hydrophilic polymer is an anionic polymer, a cationic polymer, an amphoteric polymer, and combinations thereof.

3. The polymer composition of claim 1 wherein the hydrophilic polymer is selected from the group consisting of a polyhydroxyalkyl acrylates and methacrylates;

poly(meth)acrylic acid and salts thereof;

polyvinyl alcohols;

polyoxyalkylenes;

polystyrene sulfonates;

polysaccarides;

alginates;

gums;

cellulosics;

polymers prepared from water-soluble hydrazine derivatives;

polyurethanes, mono-olefinic sulfonic acids and their salts; and

combinations thereof.

4. The polymer composition of claim 1 wherein the hydrophilic polymer is an amine-containing organic polymer selected from the group consisting of poly(quaternary amines), polylactams, polyamides, and combinations thereof .

5. The polymer composition of claim 1 wherein the hydrophilic polymer is a quaternary ammonium salt of an organic polymer.

6. The polymer composition of claim 1, wherein the hydrophilic polymer is a carboxylic acid-containing organic polymer.

46. The polymer composition of claim 1 in the form of an extruded film.

47. The polymer composition of claim 1 in the form of a foam.

48. The polymer composition of claim 1 wherein the composition is stable.

49. The polymer composition of claim 1, wherein the composition is in the form of a hydrocolloid.

60. A medical article comprising the polymer composition of claim 1.

61. A method of using a polymer composition comprising applying the polymer composition of claim 1 to a wound.

7. A polymer composition preparable by a method comprising combining components comprising:

a hydrophilic polymer;

a metal compound selected from the group consisting of a silver compound, a copper compound, a zinc compound, and combinations thereof, wherein the silver compound has a solubility of at least 0.1 gram per liter in water; and

a hydroxide source that converts the metal compound to the corresponding metal oxide;

wherein the components are combined in a manner to disperse the metal oxide within the hydrophilic polymer.

8. The polymer composition of claim 7 wherein the hydrophilic polymer is selected from the group consisting of polyhydroxyalkyl acrylates and methacrylates;

poly(meth)acrylic acid and salts thereof;

polyvinyl alcohols;

polyoxyalkylenes;

polystyrene sulfonates;

polysaccarides;

alginates;

gums;

cellulosics;

polymers prepared from water-soluble hydrazine derivatives;

polyurethanes, mono-olefinic sulfonic acids and their salts; and

combinations thereof.

9. The polymer composition of claim 7 wherein the hydrophilic polymer is an amine-containing organic polymer selected from the group consisting of poly(quaternary amines), polylactams, polyamides, and combinations thereof .

10. The polymer composition of claim 9 wherein the amine-containing organic polymer is a quaternary ammonium salt of an organic polymer.

11. The polymer composition of claim 7 wherein the composition includes water in an amount of 1 to 20 wt %, based on the total weight of the hydrophilic polymer composition.

12. The polymer composition of claim 7, wherein the hydrophilic polymer is a carboxylic acid-containing organic polymer.

50. The polymer composition of claim 7 comprising water in an amount of less than 1 weight percent, based on the total weight of the polymer composition.

59. The polymer composition of claim 7 further comprising a swelling agent.

89. A medical article comprising the polymer composition of claim 7.

90. A method of using a polymer composition comprising applying the polymer composition of claim 7 to a wound.

13. A polymer composition preparable by a method comprising combining components comprising:

a hydrophilic polymer;

an ammonia source;

a metal oxide selected from the group consisting of silver oxides, copper oxides, zinc oxide, and combinations thereof;

wherein the components are combined in a manner to disperse the metal oxide within the hydrophilic polymer; and

wherein the metal oxide particle size is less than one micron.

14. The polymer composition of claim 13 wherein the hydrophilic polymer is selected from the group consisting of polyhydroxyalkyl acrylates and methacrylates;

poly(meth)acrylic acid and salts thereof;

polyvinyl alcohols;

polyoxyalkylenes;

polystyrene sulfonates;

polysaccarides;

alginates;

gums;

cellulosics;

polymers prepared from water-soluble hydrazine derivatives;

polyurethanes, mono-olefinic sulfonic acids and their salts; and

combinations thereof.

15. The polymer composition of claim 13 wherein the ammonia source is selected from the group consisting of ammonia and ammonium salts.

16. The polymer composition of claim 15 wherein the ammonium salt is selected from the group consisting of ammonium pentaborate, ammonium acetate, ammonium carbonate, ammonium peroxyborate, ammonium tertraborate, triammonium citrate, ammonium carbamate, ammonium bicarbonate, ammonium malate, ammonium nitrate, ammonium nitrite, ammonium succinate, ammonium sulfate, ammonium tartarate, and mixtures thereof.

17. The polymer composition of claim 13 wherein the ammonia source and metal oxide form an ammonia-metal complex with a solubility greater than 0.1 gram per liter in water.

18. The polymer composition of claim 13, wherein the hydrophilic polymer is a carboxylic acid-containing organic polymer.

91. A medical article comprising the polymer composition of claim 13.

92. A method of using a polymer composition comprising applying the polymer composition of claim 13 to a wound.

93. A wound dressing comprising the composition of claim 13 coated on an apertured liquid permeable substrate wherein the composition is nonadherent.

19. A composition preparable by a method comprising combining components comprising:

a dispersion comprising absorbent hydrophilic microparticles, wherein the microparticles when in a substantially nonhydrated form have an average particle size of 10 microns or less;

a metal compound selected from the group consisting of a silver compound, a copper compound, a zinc compound, and combinations thereof, wherein the silver compound has a solubility in water of at least 0.1 gram per liter in water; and

a hydroxide source that converts the metal compound to the corresponding metal oxide;

wherein the components are combined in a manner to produce a polymer composition wherein the metal oxide is incorporated within the microparticles.

20. The polymer composition of claim 19 wherein the dispersion comprises absorbent hydrophilic microparticles, wherein the microparticles comprise an amine-containing organic polymer selected from the group consisting of a poly(quaternary amine), a polylactam, a polyamide, and combinations thereof.

21. The polymer composition of claim 19 wherein the dispersion comprises absorbent hydrophilic microparticles, wherein the microparticles comprise a carboxylic-acid containing organic polymer.

22. The polymer composition of claim 19 wherein the microparticles have an average particle size of 1 micron or less when in a substantially nonhydrated form.

23. The polymer composition of claim 19 wherein the microparticles have an average particle size of 0.5 micron or more when in a substantially nonhydrated form.

24. The polymer composition of claim 19 further comprising secondary absorbent particles having an average particle size of greater than 10 microns when in a substantially nonhydrated form.

25. The polymer composition of claim 24 wherein the secondary absorbent particles having an average particle size of greater than 10 microns are superabsorbent.

26. The polymer composition of claim 19 wherein the microparticles are superabsorbent.

27. A polymer composition preparable by a method comprising combining components comprising:

an organic polymer matrix;

a dispersion comprising absorbent hydrophilic microparticles, wherein the microparticles when in a substantially nonhydrated form have an average particle size of 10 microns or less;

a metal compound selected from the group consisting of a silver compound, a copper compound, a zinc compound, and combinations thereof, wherein the silver compound has a solubility of at least 0.1 gram per liter in water; and

a hydroxide source that converts the metal compound to the corresponding metal oxide;

wherein the components are combined in a manner to produce a polymer composition wherein the metal oxide is incorporated within the microparticles.

28. The polymer composition of claim 27 wherein the dispersion comprises absorbent hydrophilic microparticles, wherein the microparticles comprise an amine-containing organic polymer selected from the group consisting of a poly(quaternary amine), a polylactam, a polyamide, and combinations thereof.

29. The polymer composition of claim 27 wherein the dispersion comprises absorbent hydrophilic microparticles, wherein the microparticles comprise a carboxylic-acid-containing organic polymer.

30. The polymer composition of claim 27 wherein the microparticles have an average particle size of 1 micron or less when in a substantially nonhydrated form.

31. The polymer composition of claim 27 wherein the microparticles have an average particle size of 0.5 micron or more when in a substantially nonhydrated form.

32. The polymer composition of claim 27 further comprising secondary absorbent particles having an average particle size of greater than 10 microns when in a substantially nonhydrated form.

33. The polymer composition of claim 32 wherein the secondary absorbent particles having an average particle size of greater than 10 microns are superabsorbent.

34. The polymer composition of claim 27 wherein the microparticles are superabsorbent.

35. The polymer composition of claim 27 wherein the organic polymer matrix comprises an elastomeric polymer.

36. The polymer composition of claim 35 wherein the elastomeric polymer is selected from the group consisting of a polyisoprene, a styrene-diene block copolymer, a natural rubber, a polyurethane, a polyether-block-amide, a poly-alpha-olefin, a (C1-C20) acrylic ester of meth(acrylic) acid, an ethylene-octene copolymer, and combinations thereof.

37. The polymer composition of claim 27 wherein the organic polymer matrix comprises a thermoplastic polymer.

38. The polymer composition of claim 37 wherein the thermoplastic polymer is a polyolefin.

39. The polymer composition of claim 27 wherein the organic polymer matrix comprises a hydrophilic polymer selected from the group consisting of a polysaccharide, a polyether, a polyurethane, a polyacrylate, a cellulosic, and an alginate.

40. The polymer composition of claim 27 wherein the hydrophilic polymer microparticles comprise a quaternary ammonium salt of an organic polymer.

41. The polymer composition of claim 40 wherein the microparticles comprise a cationic homopolymer of the methyl chloride quaternary salt of 2-(dimethylamino)ethyl methacrylate.

42. The polymer composition of claim 27 further comprising an additive selected from the group consisting of a plasticizer, a tackifier, a crosslinking agent, a stabilizer, an extruding aid, a filler, a pigment, a dye, a swelling agent, a foaming agent, a chain transfer agent, and combinations thereof.

43. The polymer composition of claim 27 wherein the organic polymer matrix comprises a mixture of two or more polymers.

44. The polymer composition of claim 27 wherein the microparticles are present in an amount of 1 wt-% to 60 wt-%, based on the total weight of the polymer composition.

45. The polymer composition of claim 27 wherein the composition includes water in an amount of 1 wt-% to 20 wt-%, based on the total weight of the polymer composition.

51. The polymer composition of claim 27 wherein the hydrophobic material forms a discontinuous phase and the hydrophilic polymer forms a continuous phase.

52. The polymer composition of claim 27 wherein the hydrophilic polymer forms a discontinuous phase and the hydrophobic material forms a continuous matrix.

53. The polymer composition of claim 52 wherein the hydrophobic material is liquid at room temperature.

54. The polymer composition of claim 53 wherein the hydrophobic material is mineral oil.

55. The polymer composition of claim 52 wherein the hydrophobic material is solid at room temperature.

56. The polymer composition of claim 52 wherein the hydrophobic material comprises an elastomeric polymer.

57. The polymer composition of claim 56 wherein the elastomeric polymer is selected from the group consisting of a polyisoprene, a styrene-diene block copolymer, a natural rubber, a polyurethane, a polyether-block-amide, a poly-alpha-olefin, a (C1-C20) acrylic esters of meth(acrylic) acid, an ethylene-octene copolymer, and combinations thereof.

58. The polymer composition of claim 56 wherein the elastomeric polymer is selected from the group consisting of styrene-isoprene-styrene (SIS), styrene-butadiene-styrene (SBS), styrene-ethylene-propylene-styrene (SEPS), and styrene-ethylene-butylene-styrene (SEBS).

67. A wound dressing comprising the composition of claim 27 coated on an apertured liquid permeable substrate wherein the composition is nonadherent.

62. A method of making a polymer composition, wherein the method comprises:

combining a dispersion comprising hydrophilic organic microparticles with water and a metal compound under conditions effective to distribute substantially all of the metal compound in the hydrophilic organic microparticles, wherein the metal compound is selected from the group consisting of a silver compound, a copper compound, a zinc compound, and combinations thereof;

wherein the silver compound has a solubility in water of at least 0.1 gram per liter in water;

adding a hydroxide source to convert the metal compound to the corresponding metal oxide;

optionally adding a secondary organic polymer to the dispersion; and

optionally removing a substantial portion of the water.

63. The method of claim 62, further comprising the step of adding an oxidizing agent to form a higher valence metal oxide.

64. The method of claim 62, further comprising subjecting the polymer composition to radiation.

65. The method of claim 62, further comprising extruding or molding the composition.

66. A method of making a polymer composition, wherein the method comprises:

combining monomers for a hydrophilic organic polymer with a metal compound under conditions effective to polymerize the monomers and distribute substantially all of the metal compound within the hydrophilic organic polymer, wherein the metal compound is selected from the group consisting of a silver compound, a copper compound, a zinc compound, and combinations thereof;

wherein the silver compound has a solubility in water of at least 0.1 gram per liter in water;

adding a hydroxide source to convert the bioactive agent to the corresponding metal oxide; and

optionally adding a secondary organic polymer to the hydrophilic organic polymer.

68. A medical article comprising a substrate impregnated with one or more metal oxides of silver, copper and zinc wherein the impregnated substrate has less than 1 N/cm peel strength to steel and does not adhere to wound tissue.

69. A medical article comprising a substrate impregnated with one or more metal oxides of silver, copper and zinc with an average particle size less than 1 micron dispersed within a hydrocolloid.

70. A method of forming silver oxide in a hydrocolloid, the method comprising:

providing a mixture of a hydrocolloid and a solution of the silver compound with a solubility of at least 0.1 gram per liter in water;

adding a hydroxide source to form an metal oxide of silver (I);

wherein the silver oxide is dispersed within the hydrocolloid.

71. The method of claim 70, further comprising the step of adding an oxidizing agent to form a higher valence oxide of silver.

72. The method of claim 70, further comprising the step of adding a hydrophobic polymer.

73. The medical article of claim 70 wherein the hydrocolloid has a particle size less than 10 microns.

74. The medical article of claim 72 wherein the hydrophobic polymer comprises styrene-isoprene-styrene.

75. A polymer composition comprising:

a hydrophilic polymer; and

a silver oxide;

wherein the silver oxide is dispersed within the hydrophilic polymer; and

wherein substantially all of the silver oxide has a average particle size less than one micron.

76. A method of making a polymer composition comprising:

combining a hydrophilic polymer,

a metal compound selected from the group consisting of a silver compound, a copper compound, a zinc compound, and combinations thereof, wherein the silver compound has a solubility in water of at least 0.1 gram per liter in Water; and

a hydroxide source that converts the metal compound to the corresponding metal oxide; and

dispersing the metal oxide within the hydrophilic polymer.

77. The method of claim 76 wherein the hydrophilic polymer is selected from the group consisting of polyhydroxyalkyl acrylates and methacrylates;

poly(meth)acrylic acid and salts thereof;

polyvinyl alcohols;

polyoxyalkylenes;

polystyrene sulfonates;

polysaccarides;

alginates;

gums;

cellulosics;

polymers prepared from water-soluble hydrazine derivatives;

polyurethanes, mono-olefinic sulfonic acids and their salts; and

combinations thereof.

78. The method of claim 76 wherein the hydrophilic polymer is an amine-containing organic polymer selected from the group consisting of poly(quaternary amines), polylactams, polyamides, and combinations thereof.

79. The method of claim 78 wherein the amine-containing organic polymer is a quaternary ammonium salt of an organic polymer.

80. The method of claim 76 wherein the hydrophilic polymer comprises absorbent hydrophilic microparticles, wherein the microparticles comprise a carboxylic-acid containing organic polymer.

81. The method of claim 76, wherein the hydroxide source is added after combining the bioactive agent and the hydrophilic polymer.

82. The method of claim 76, further comprising combining an oxidizing agent with the hydrophilic polymer, the bioactive agent, and the hydroxide source.

83. The method of claim 82, wherein the oxidizing agent is added after combining the hydrophilic polymer, the bioactive agent, and the hydroxide source.

84. A method of making a polymer composition, comprising:

combining a hydrophilic polymer;

an ammonia source; and

a metal oxide selected from the group consisting of silver oxides, copper oxides, zinc oxides, and combinations thereof; and

dispersing the metal oxide within the hydrophilic polymer;

wherein the metal oxide particle size is less than one micron.

85. The method of claim 84, wherein the ammonia source and metal oxide are combined before combining with the hydrophilic polymer.

86. The method of claim 84, further comprising combining an oxidizing agent with the hydrophilic polymer, the ammonia source, and the metal oxide.

87. The method of claim 86, wherein the oxidizing agent is added after combining the hydrophilic polymer, the ammonia source, and the metal oxide.

88. The method of claim 84, further comprising combining the components in the presence of water and removing a substantial portion of the water.