Antibacterial coatings that inhibit biofilm formation on implants
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61F-002/02
A61L-027/34
A61L-027/50
A01N-033/12
출원번호
US-0647107
(2012-10-08)
등록번호
US-9089407
(2015-07-28)
발명자
/ 주소
Schaer, Thomas P.
Stewart, Suzanne
Klibanov, Alexander M.
출원인 / 주소
Massachusetts Institute of Technology
대리인 / 주소
Pabst Patent Group LLP
인용정보
피인용 횟수 :
0인용 특허 :
51
초록▼
Orthopedic and dental implants coated with an antibacterial coating and methods of making and using, are described herein. The implant can be coated with a hydrophobic, polycationic antibacterial polymer. The polymer can be covalently or non-covalently associated with the surface; however, in partic
Orthopedic and dental implants coated with an antibacterial coating and methods of making and using, are described herein. The implant can be coated with a hydrophobic, polycationic antibacterial polymer. The polymer can be covalently or non-covalently associated with the surface; however, in particular embodiments, the polymer is non-covalently associated with the surface. As shown in the examples below, clinical observations, digital radiography, and a battery of well-accepted ex vivo analytical methods show that the presence of a hydrophobic polycationic polymer coating, such as N,N-dodecyl,methyl-PEI coating on the surface of a metal implant, was effective in eliminating the clinical signs of infection in vivo in a large animal infection model. Moreover, the coated plates supported bone healing, and in fact decreased healing times, even in the presence of significant bacterial contamination compared to a control.
대표청구항▼
1. An implant comprising a polymeric coating on an outer surface of the implant, wherein the implant is selected from the group consisting of prosthetic implants, orthopedic implants, ear, nose, and throat implants, and cardiovascular implants, wherein the polymer forming the coating is an antimicro
1. An implant comprising a polymeric coating on an outer surface of the implant, wherein the implant is selected from the group consisting of prosthetic implants, orthopedic implants, ear, nose, and throat implants, and cardiovascular implants, wherein the polymer forming the coating is an antimicrobial hydrophobic polycationic polymer selected from the group consisting of poly(4-vinyl-N-alkylpyridine), N,N-dialkylated branched polyethylene iminie, and N,N-dialkylated linear polyethylene imine polymers. 2. The implant of claim 1, wherein the implant comprises metallic material, metal oxides, synthetic or natural, cross-linked or non-crosslinked, polymeric materials, ceramics, porcelain, allogenic or xenogenic bone or bone matrix; genetically engineered bone; and combinations thereof. 3. The implant of claim 2, wherein the metallic material is selected from the group consisting of NiTi alloys, stainless steel, titanium or alloys thereof. 4. The implant of claim 2, wherein the implant comprises a non-degradable polymeric material. 5. The implant of claim 4, wherein the implant comprises a polymeric material selected from the group consisting of polypropylene (PP), polyethylene (PE), polyacetylene, cross-linked or non-crosslinked polystyrene, styrene-butadiene rubber, polytetrafluoroethylene, poly(vinyl chloride) (PVC), polyolefin copolymers, poly(methyl methacrylate), polyphenylene, polyacrylonitrile, carbon fiber, and blends or copolymers thereof. 6. The implant of claim 2, wherein the implant comprises a biodegradable polymeric material. 7. The implant of claim 6, wherein the implant comprises a polymeric material selected from the group consisting of collagen, cellulosic polymers, polysaccharides, poly(glycolic acid), poly(L-lactic acid) (PLLA), poly(lactide-co-glycolide) (PLGA), a polydioxanone (PDA), or racemic poly(lactic acid), polyurethane (PU), polycarbonates, polyetherketone (PEEK), polyesters, and polyamides (nylon). 8. The implant of claim 1 wherein the orthopedic implant is selected from the group consisting of Kirschner wire, bone plates, screws, pins, tacs, rods, nails, nuts, bolts, washers, spikes, buttons, wires, fracture plates, endo- and exoprostheses, intraosseous transcutaneous prostheses, spacers, mesh, implant abutments, anchors, barbs, clamps, suture, tubes of any geometry, and combinations thereof. 9. The implant of claim 1, wherein the ear, nose, or throat implant is selected from the group consisting of ear tubes, endrotracheal tubes, ventilation tubes, cochlear implants and bone anchored hearing devices. 10. The implant of claim 1, wherein the cardiovascular implant is selected from the group consisting of cardiac valves, alloplastic vessel wall supports, and total artificial heart implants. 11. The implant of claim 1 wherein the N,N-dialkylated branched polyethylene imine or N,N-dialkylated linear polyethylene imine is N,N-dodecyl,methyl-PEI or N,N-hexyl,methyl-PEI. 12. The implant of claim 1, wherein the weight average molecular weight of the N,N-dialkylated branched polyethylene imine or N,N-dialkylated linear polyethylene imine polymer is at least 20,000 g/mol. 13. The implant of claim 1, wherein the thickness of the polymer coating is between about 1 nm and about 1 cm. 14. The implant of claim 1, wherein the polymer coating is non-covalently associated with one or more outer surfaces of the implant. 15. The implant of claim 1, wherein the polymer coating is covalently associated with one or more outer surfaces of the implant. 16. A method of preventing infection while treating hard or soft tissue, the method comprising implanting the implant of claim 1. 17. The method of claim 16, wherein the coating is applied to the implant immediately prior to implantation. 18. A method of treating hard or soft tissue in the presence of an infection, the method comprising implanting the implant of claim 1. 19. The method of claim 18, wherein the coating is applied to the implant immediately prior to implantation. 20. The implant of claim 1 wherein the poly(4-vinyl-N-alkylpyridine) has the formula: wherein, R for each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkenyl, acyl, aryl, carboxylate, alkoxycarbonyl, aryloxycarbonyl, carboxamido, alkylamino, acylamino, alkoxyl, acyloxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, (alkylamino)alkyl, thio, alkylthio, thioalkyl, (alkylthio)alkyl, carbamoyl, urea, thiourea, sulfonyl, sulfonate, sulfonamido, sulfonylamino, and sulfonyloxy; R′ is selected from the group consisting of an alkyl, an alkylidene tethered to the surface, and an acyl tethered to the surface;Z− is independently selected from the group consisting of Cl, Br, or I; andn is an integer less than or equal to about 1500. 21. The implant of claim 20, wherein R′ is selected from the group consisting of a C4-C12 alkyl, C6-C12 alkyl, and C6-C10 alkyl. 22. The implant of claim 1, wherein the weight average molecular weight of the poly(4-vinyl-N-alkylpyridine) polymer is at least 50,000 g/mol.
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