Polymer compositions containing colloids of silver salts

• US 20030049300A1
• Filed: 08/05/2002
• Published: 03/13/2003
• Est. Priority Date: 12/15/1999
• Status: Active Grant

• Current Assignee: C.R. Bard, Inc. (Becton, Dickinson & Co)
• Original Assignee: C.R. Bard, Inc. (Becton, Dickinson & Co)
• Inventors: Terry, Richard N.
• Granted Patent: US 6,949,598 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• 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. An article of manufacture comprising a substrate and an antimicrobial polymer coating wherein the polymer coating comprises one or more polymers and a colloid wherein the colloid comprises salts of one or more oligodynamic metals

2. The article of claim 1 wherein the substrate is a medical device.

3. The article of claim 2 wherein the medical device comprises a catheter, an endotracheal tube, a tracheostomy tube, a wound drainage device, a wound dressing, a stent, an implant, an intravenous catheter, a medical adhesive, a suture, a shunt, a glove, a condom, a contact lens, a gastrostomy tube, medical tubing, cardiovascular products, heart valves, pacemaker leads, a guidewire, or urine collection devices.

4. The article of claim 3 wherein the medical device is a catheter.

5. The article 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 a hydrophobic polymers, or a combination of both hydrophilic and hydrophobic polymers.

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

7. The article of claim 5 wherein the hydrophobic polymer is selected from the group consisting of 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, cellulose, and mixtures, derivatives, and copolymers thereof.

8. The article of claim 1 wherein the colloid comprises at least one silver salt.

9. The article of claim 8 wherein the silver salt is selected from the group selected from the group consisting 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, and silver gluconate.

10. The article of claim 1 wherein the colloid comprises the salt of more than one oligodynamic metal.

11. The article of claim 10 wherein the oligodynamic metal salts comprise salts having different solubilities in water.

12. The article of claim 11 wherein the oligodynamic metal salts comprise silver lactate, silver acetate, silver citrate, silver chloride, and silver iodide.

13. An article of manufacture comprising one or more polymers and a colloid wherein the colloid comprises salts of one or more oligodynamic metals.

14. A composition comprising a polymer and a colloid wherein the colloid comprises salts of one or more oligodynamic metals.

15. The composition of claim 14 wherein the colloid comprises at least one silver salt.

16. The composition of claim 15 wherein the silver salt is selected from the group selected from the group consisting 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, and silver gluconate.

17. The composition of claim 14 wherein the colloid comprises the salt of more than one oligodynamic metal.

18. The composition of claim 17 wherein the oligodynamic metal salts comprise salts having different solubilities in water.

19. The composition of claim 18 wherein the oligodynamic metal salts comprise silver lactate, silver acetate, silver citrate, silver chloride, and silver iodide.

20. The composition of claim 14 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.

21. The composition of claim 20 wherein the hydrophilic polymer is selected from the group consisting of polyurethanes, polyvinylpyrrolidones, polyvinyl alcohols, polyethylene glycols, polypropylene glycols, polyoxyethylenes, polyacrylic acid, polyacrylamide, carboxymethyl cellulose, dextrans, polysaccharides, starches, guar, xantham and other gums, collagen, gelatins, biological polymers, and mixtures and copolymers thereof.

22. The composition of claim 20 wherein the hydrophobic polymer is selected from the group consisting of 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, cellulose, and mixtures, derivatives, and copolymers thereof.

23. A process for the manufacture of an antimicrobial composition comprising the steps of:

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

b) forming in the polymer solution a colloid comprising contacting

1) a solution of salt A which comprises one or more salts of oligodynamic metals, and

2) a solution of salt B which comprises additional salts that reacts with salt A to form a fine colloidal precipitate.

24. The process of claim 23 wherein the colloid in step (b) is formed separately and then combined with the polymer solution.

25. The process of claim 23 wherein the colloid is formed in situ in the polymer solution.

26. The process of claim 23 wherein salt A comprises salts of metals selected from the group consisting of silver, platinum, gold, zinc, copper, cerium, gallium, palladium, rhodium, iridium, ruthenium, and osmium.

27. The process of claim 23 wherein salt B comprises anions selected from the group consisting of 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, and thiosulfates.

28. The process of claim 23 wherein salt B comprises cations selected from the group consisting of calcium, sodium, lithium, aluminum, magnesium, potassium, and manganese.

29. The process of claim 23 wherein the colloid formed in step (b) comprises at least one silver salt.

30. The process of claim 29 wherein the silver salt is selected from the group consisting of 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, and silver gluconate.

31. The process of claim 23 wherein the colloid formed in step (b) comprises salts having different solubilities in water.

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

33. The process of claim 23 wherein the polymer is a hydrophilic polymer, one or more a hydrophobic polymers, or a combination of both hydrophilic and hydrophobic polymers.

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

35. A method for the manufacture of an article comprising dipping or spraying a substrate with a coating composition wherein the coating composition comprises polymers, monomers, or any combination thereof, and a colloid comprising salts of one or more oligodynamic metals.

36. A method for the manufacture of an article comprising the steps of forming a solution, dispersion, of combination thereof of more or more polymers containing a colloid wherein the colloid comprises salts of one or more oligodynamic metals;

and

2) drying the solution to create a solid polymeric article.

37. A method for the manufacture of an article comprising the steps of forming a composition that comprises a solution, dispersion, of combination thereof of one or more polymers containing a colloid wherein the colloid comprises salts of one or more oligodynamic metals;

2) drying the composition; and

3) processing the composition with the application of heat to form the article.

38. A method for the manufacture of an article comprising the steps of forming a composition that comprises solution, dispersion, of combination thereof of one or more polymers containing a colloid wherein the colloid comprises salts of one or more oligodynamic metals;

2) compounding the composition formed in step (1) with one or more polymers; and

3) processing the composition formed in step (2) with the application of heat to form the article.

39. A method for the manufacture of an article comprising dipping a form in a composition comprising polymers, monomers, or any combination thereof, and a colloid comprising salts of one or more oligodynamic metals.

40. A method for the manufacture of an article comprising casting a composition comprising polymers, monomers, or any combination thereof, and a colloid comprising salts of one or more oligodynamic metals.