Polymer compositions containing colloids of silver salts

• US 6,949,598 B2
• Filed: 08/05/2002
• Issued: 09/27/2005
• Est. Priority Date: 12/15/1999
• Status: Expired due to Term

• Current Assignee: C.R. Bard, Inc. (Becton, Dickinson & Co)
• Original Assignee: C.R. Bard, Inc. (Becton, Dickinson & Co)
• Inventors: Terry, Richard N.
• Primary Examiner(s): SZEKELY, PETER A
• Application Number:
  US10/212,505
• Publication Number:
  US 20030049300A1
• Time in Patent Office: 1,149 Days
• Field of Search: 524398-400, 524/403, 524406-407, 524/413, 524430-437
• US Class Current: 524/398
• 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 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• 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: 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 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/0056 provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
• CPC Class Codes: Y10S 604/905 Aseptic connectors or couplings, e.g. frangible, piercable

Abstract

The present invention relates to antimicrobial compositions, methods for the production of these compositions, and use of these compositions with medical devices, such as catheters, and implants. The compositions of the present invention advantageously provide varying release kinetics for the active ions in the compositions due to the different water solubilities of the ions, allowing antimicrobial release profiles to be tailored for a given application and providing for sustained antimicrobial activity over time. More particularly, the invention relates to polymer compositions containing colloids comprised of salts of one or more oligodynamic metal, such as silver. The process of the invention includes mixing a solution of one or more oligodynamic metal salts with a polymer solution or dispersion and precipitating a colloid of the salts by addition of other salts to the solution which react with some or all of the first metal salts. The compositions can be incorporated into articles or can be employed as a coating on articles such as medical devices.

Claims

1. A composition comprising:

one or more polymers; and

,

a colloid comprising a plurality of oligodynamic metal salts, wherein the colloid comprises at least one silver salt and wherein said oligodynamic metal salts have different solubilities in water.

2. The composition of claim 1 wherein the silver salt is selected from silver chloride, silver iodide, silver citrate, silver lactate, silver acetate, silver propionate, silver salicylate, silver bromide, silver ascorbate, silver laurel sulfate, silver phosphate, silver sulfate, silver benzoate, silver carbonate, silver sulfadiazine, silver gluconate, or combinations thereof.

3. The composition of claim 1, wherein the colloid comprise two or more silver salts and wherein the silver salts have different solubilities in water.

4. The composition of claim 1 wherein the silver salts comprise silver lactate, silver acetate, silver citrate, silver chloride, and silver iodide.

5. The composition of claim 1, wherein the polymer comprises one or more hydrophilic polymers that are soluble in water or in an organic solvent containing water, one or more hydrophobic polymers, or a combination of both hydrophilic and hydrophobic polymers.

6. The composition of claim 5 wherein the hydrophilic polymer is selected from polyurethanes, polyvinylpyrrolidones, polyvinyl alcohols, polyethylene glycols, polypropylene glycols, polyoxyethylenes, polyacrylic acid, polyacrylamide, carboxymethyl cellulose, cellulose, dextrans, polysaccharides, starches, guar, xantham and other gums, collagen, gelatins, biological polymers, or mixtures or copolymers thereof.

7. The composition of claim 5 wherein the hydrophobic polymer is selected from polytetrafluoroethylene, polyvinyl chloride, polyvinylacetate, poly(ethylene terephthalate), silicone, polyesters, polyamides, polyureas, styrene-block copolymers, polymethyl methacrylate, polyacrylates, acrylic-butadiene-styrene copolymers, polyethylene, polystyrene, polypropylene, natural and synthetic rubbers, acrylonitrile rubber, and mixtures, or copolymers thereof.

8. A composition comprising a polymer and a colloid wherein:

the colloid comprises two or more silver salts having different solubilities in water; and

the polymer is selected from polyurethanes, polyvinylpyrrolidones, polyvinyl alcohols, polyethylene glycols, polypropylene glycols, polyoxyethylenes, polyacrylic acids, polyacrylamides, polysaccharides, cellulose, gums, thickeners, collagens, polytetrafluoroethylene, polyvinyl chloride, polyvinylacetate, poly(ethylene terephthalate), silicone, polyesters, polyamides, polyureas, styrene-block copolymers, polymethyl methacrylate, acrylic-butadiene-styrene copolymers, polyethylene, polystyrene, polypropylene, natural and synthetic rubbers, acrylonitrile rubber, and mixtures or copolymers thereof.

9. The composition of claim 8 wherein the silver salts are selected from silver chloride, silver iodide, silver citrate, silver lactate, silver acetate, silver propionate, silver salicylate, silver bromide, silver ascorbate, silver laurel sulfate, silver phosphate, silver sulfate, silver oxide, silver benzoate, silver carbonate, silver sulfadiazine, silver gluconate, or combinations thereof.

10. The composition of claim 8 wherein the silver salts comprise silver lactate, silver acetate, silver citrate, silver chloride, and silver iodide.

11. The composition of claim 8, wherein the polymer comprises one or more hydrophilic polymers that are soluble in water or in an organic solvent containing water, one or more hydrophobic polymers, or a combination of both hydrophilic and hydrophobic polymers.

12. The composition of claim 11 wherein the hydrophilic polymer is selected from polyurethanes, polyvinylpyrrolidones, polyvinyl alcohols, polyethylene glycols, polypropylene glycols, polyoxyethylenes, polyacrylic acid, polyacrylamide, carboxymethyl cellulose, cellulose, dextrans, polysaccharides, starches, guar, xantham and other gums, collagen, gelatins, biological polymers, or mixtures or copolymers thereof.

13. The composition of claim 11 wherein the hydrophobic polymer is selected from polytetrafluoroethylene, polyvinyl chloride, polyvinylacetate, poly(ethylene terephthalate), silicone, polyesters, polyamides, polyureas, styrene-block copolymers, polymethyl methacrylate, polyacrylates, acrylic-butadiene-styrene copolymers, polyethylene, polystyrene, polypropylene, natural and synthetic rubbers, acrylonitrile rubber, or mixtures, or copolymers thereof.

14. A process for the manufacture of a composition comprising:

a) forming a solution, dispersion, or combination thereof of one or more polymers; and

,

b) forming in the polymer solution, dispersion, or combination thereof a colloid;

wherein forming the colloid comprises contacting;

1) a solution of component A which comprises one or more salts, one or more oxides, or a combination of at least one salt and at least one oxide of one or more oligodynamic metals; and

2) a solution of component B which comprises a plurality of salts, a plurality of oxides, or a combination of at least one salt and at least one oxide that react with component A to form a fine colloidal precipitate, wherein the colloid formed in step (b) comprises salts or oxides having different solubilities in water.

15. The process of claim 14 wherein the colloid is formed in situ in the polymer solution.

16. The process of claim 14 wherein component A comprises salts or oxides of metals selected from silver, platinum, gold, zinc, copper, cerium, gallium, palladium, rhodium, iridium, ruthenium, or osmium.

17. The process of claim 14 wherein component B comprises anions selected from acetates, ascorbates, benzoates, bitartrates, bromides, carbonates, chlorides, citrates, folates, gluconates, iodates, iodides, lactates, laurates, oxalates, oxides, palmitates, perborates, phenosulfonates, phosphates, propionates, salicylates, stearates, succinates, sulfadiazines, sulfates, sulfides, sulfonates, tartrates, thiocyanates, thioglycolates, or thiosulfates.

18. The process of claim 14 wherein component B comprises cations selected from calcium, sodium, lithium, zinc, copper, aluminum, magnesium, potassium, or manganese.

19. The process of claim 14 wherein the colloid formed in step (b) comprises at least one silver salt.

20. The process of claim 14 wherein the colloid formed in step (b) is selected from silver chloride, silver iodide, silver citrate, silver lactate, silver acetate, silver propionate, silver salicylate, silver bromide, silver ascorbate, silver laurel sulfate, silver phosphate, silver sulfate, silver oxide, silver benzoate, silver carbonate, silver sulfadiazine, silver gluconate, or combinations thereof.

21. The process of claim 14 wherein the colloid formed in step (b) comprises silver lactate, silver acetate, silver citrate, silver chloride, and silver iodide.

22. The process of claim 14 wherein the polymer is one or more hydrophilic polymers, one or more hydrophobic polymers, or a combination of both hydrophilic and hydrophobic polymers.

23. The process of claim 14 wherein the polymer solution is formed by dissolving the polymer in supercritical liquids.

24. A process for the manufacture of a composition, comprising the steps of:

a) forming a solution, dispersion, or combination thereof of one or more polymers, wherein the polymer is selected from the group consisting of polyurethanes, polyvinylpyrrolidones, polyvinyl alcohols, polyethylene glycols, polypropylene glycols, polyoxyethylenes, polyacrylic acids, polyacrylamides, polysaccharides, cellulose, gums, thickeners, collagens, polytetrafluoroethylene, polyvinyl chloride, polyvinylacetate, poly(ethylene terephthalate), silicone, polyesters, polyamides, polyureas, styrene-block copolymers, polymethyl methacrylate, acrylic-butadiene-styrene copolymers, polyethylene, polystyrene, polypropylene, natural and synthetic rubbers, acrylonitrile rubber, and mixtures and copolymers thereof; and

,

b) forming in the polymer solution a colloid;

wherein forming the colloid comprises contacting;

a solution of component A which comprises one or more salts, one or more oxides, or a combination of at least one salt and at least one oxide of one or more oligodynamic metals; and

a solution of component B which comprises one or more salts, one or more oxides, or a combination of at least one salt and at least one oxide that reacts with component A to form a fine colloidal precipitate, wherein the colloid formed in step (b) comprises salts or oxides having different solubilities in water.

25. The process of claim 24 wherein the colloid is formed in situ in the polymer solution.

26. The process of claim 24 wherein component A comprises salts or oxides of metals selected from silver, platinum, gold, zinc, copper, cerium, gallium, palladium, rhodium, iridium, ruthenium, or osmium.

27. The process of claim 24 wherein component B comprises anions selected from acetates, ascorbates, benzoates, bitartrates, bromides, carbonates, chlorides, citrates, folates, gluconates, iodates, iodides, lactates, laurates, oxalates, oxides, palmitates, perborates, phenosulfonates, phosphates, propionates, salicylates, stearates, succinates, sulfadiazines, sulfates, sulfides, sulfonates, tartrates, thiocyanates, thioglycolates, or thiosulfates.

28. The process of claim 24 wherein component B comprises cations selected from calcium, sodium, lithium, zinc, copper, aluminum, magnesium, potassium, or manganese.

29. The process of claim 24 wherein the colloid formed in step (b) comprises at least one silver salt.

30. The process of claim 24 wherein the colloid formed in step (b) is selected from silver chloride, silver iodide, silver citrate, silver lactate, silver acetate, silver propionate, silver salicylate, silver bromide, silver ascorbate, silver laurel sulfate, silver phosphate, silver sulfate, silver oxide, silver benzoate, silver carbonate, silver sulfadiazine, silver gluconate, or combinations thereof.

31. The process of claim 24 wherein the colloid formed in step (b) comprises silver lactate, silver acetate, silver citrate, silver chloride, and silver iodide.

32. The process of claim 24 wherein the polymer is one or more hydrophilic polymers, one or more hydrophobic polymers, or a combination of both hydrophilic and hydrophobic polymers.

33. The process of claim 24 wherein the polymer solution is formed by dissolving the polymer in supercritical liquids.

34. A composition comprising:

one or more polymers; and

,

a colloid comprising a plurality of oligodynamic metal salts, wherein the oligodynamic metal salts comprise salts having different solubilities in water and wherein the oligodynamic metal salts are selected from silver lactate, silver acetate, silver citrate, silver chloride, or silver iodide.