Post-charging of zeolite doped plastics with antimicrobial metal ions

• US 9,492,584 B2
• Filed: 11/24/2010
• Issued: 11/15/2016
• Est. Priority Date: 11/25/2009
• Status: Active Grant

• Current Assignee: Difusion Technologies Incorporated
• Original Assignee: Difusion Technologies Incorporated
• Inventors: Crudden, Joseph J., Johns, Derrick
• Primary Examiner(s): Oswecki, Jane C
• Application Number:
  US13/511,176
• Publication Number:
  US 20120315340A1
• Time in Patent Office: 2,183 Days
• Field of Search: 424/618, 424/684, 623/11, 623/16.11, 623/17.17, 623/17.18, 623/17.19, 623/23.56, 623/23.59, 604/890.1, 604/892.1, 423/700
• US Class Current: 1/1
• CPC Class Codes: A61L 2202/21 Pharmaceuticals, e.g. medicaments, artificial body parts
• 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 27/10 Ceramics or glasses
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/443 with carbon fillers
• CPC Class Codes: A61L 27/446 with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: C08L 71/00 Compositions of polyethers obtained by reactions forming an ether link in the main chain of polyacetals C08L59/00; of epoxy resins C08L63/00; of polythioether-ethers C08L81/02; of polyether-sulfones C08L81/06; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 71/12 Polyphenylene oxides

Abstract

Methods of post-loading ceramic particles with antimicrobial metal cations are disclosed. In certain embodiments, the post-loaded particles are zeolites, wherein the zeolites have been incorporated into a resin and the combination is used as an implantable device. In certain embodiments, the polymer is a thermoplastic polymer such as polyaryletheretherketone (PEEK). In certain embodiments, the source of antimicrobial activity includes ion-exchangeable cations contained in a zeolite. In certain embodiments, disclosed are methods of imparting antimicrobial activity to devices by controlling the delivery of certain cations through ion-exchange via a zeolite incorporated in the device.

Claims

1. A method of post-charging ceramic particles with antimicrobial metal cations, comprising incorporating uncharged A-type zeolite particles having a three dimensional skeletal structure represented by the formula:

XM_2/nO·

Al₂O₃·

YSiO₂·

ZH₂O, wherein M represents an ion-exchangeable ion, n represents the atomic valency of the ion-exchangeable ion, X and Y represent coefficients of a metal oxide of an ion-exchangeable ion and silica dioxide respectively, and Z represents the number of water of crystallization into a thermoplastic polymer, thereafter charging said zeolite particles with one or more metal cations, and establishing the rate of release of said one or more metal ions from said zeolite particles in the thermoplastic polymer;

wherein the amount of said uncharged A-type zeolite particles incorporated into said thermoplastic polymer, and the amount of said one or more metal cations charged to said zeolite particles, are effective to achieve antimicrobial activity when said thermoplastic polymer is implanted in the body of a patient and contacts bodily tissue or fluid to release said one or more metal cations from said thermoplastic polymer via ion-exchange.

2. The method of claim 1, wherein said one or more metal cations are selected from the group consisting of silver, zinc and copper.

3. The method of claim 1, further comprising forming said zeolite particles and thermoplastic polymer into an implant having a surface which contacts body tissue or fluid when implanted, and wherein at least some of said zeolite particles are present at said surface and capable of releasing said metal cations in an antimicrobially effective amount.

4. The method of claim 1, wherein said metal cations are present at a level less than the ion-exchange capacity of the zeolite particles.

7. The method of claim 1 or 5, wherein said thermoplastic polymer comprises reinforced PEEK.

8. The method of claim 7, wherein said reinforced PEEK is carbon fiber-reinforced PEEK.

9. The method of claim 1, wherein said thermoplastic polymer comprises PEEK that has a porosity between 50% and 85% by volume of said PEEK.

5. A method of imparting antimicrobial activity to a device by controlling the release of antimicrobial cations from said device through ion-exchange, comprising incorporating A-type zeolite particles having a three dimensional skeletal structure represented by the formula:

XM_2/nO·

Al₂O₃·

YSiO₂·

ZH₂O, wherein M represents an ion-exchangeable ion, n represents the atomic valency of the ion-exchangeable ion, X and Y represent coefficients of a metal oxide of an exchangeable ion and silica dioxide respectively, and Z represents the number of water of crystallization into a thermoplastic polymer, subsequently charging said zeolite particles with one or more metal cations, and establishing the rate of release of said one or more metal ions from said zeolite particles in the thermoplastic polymer;

wherein the amount of said uncharged A-type zeolite particles incorporated into said thermoplastic polymer, and the amount of said one or more metal cations charged to said zeolite particles, are effective to achieve antimicrobial activity when said thermoplastic polymer is implanted in the body of a patient and contacts bodily tissue or fluid to release said one or more metal cations from said thermoplastic polymer via ion-exchange.

6. The method of claim 5, wherein said metal cations comprise silver.

10. A method of forming an implant which comprises zeolite particles with antimicrobial metal cations, said implant having a surface, said method comprising:

a. incorporating uncharged A-type zeolite particles having a three dimensional skeletal structure represented by the formula;

XM_2/nO·

Al₂O₃·

YSiO₂·

ZH₂O, wherein M represents an ion-exchangeable ion, n represents the atomic valency of the ion-exchangeable ion, X represents a coefficient of a metal oxide of an ion-exchangeable ion and Y represents a coefficient of silica dioxide, and Z represents the number of water of crystallization into a thermoplastic polymer such that at least some of said zeolite particles are present at said implant surface;

b. forming said zeolite particles and thermoplastic polymer into an implant having a surface which contacts body tissue or fluid when implanted into a living body;

c. providing an infusion solution comprising antimicrobial metal cation salt and nitric acid;

d. exposing said implant to said infusion solution to load said zeolite particles with said antimicrobial metal cation and to etch said implant surface with said acid; and

establishing the rate of release of said one or more metal ions from said zeolite particles in the thermoplastic polymer;

wherein said zeolite particles at said implant surface are capable of releasing said metal cations in an antimicrobially effective amount when said surface contacts said body tissue or fluid.