Resurrection Of Antibiotics That MRSA Resists By Silver-Doped Bioactive Glass-Ceramic Particles

Patent metadata

Field	Value
Publication number	US-2020330510-A1
Application number	US-202016833092-A
Country	US
Kind code	A1
Filing date	Mar 27, 2020
Priority date	Mar 29, 2019
Publication date	Oct 22, 2020
Grant date	—

Abstract

A method of treating a bacterial infection including bacteria that have become resistant to an antibiotic in a subject in need thereof is provided. The method includes administering to the subject a safe and therapeutically effective amount of the antibiotic and a reviving agent selected from the group consisting of glass-ceramic particles, silver ions, and combinations thereof. The reviving agent restores antibiotic activity to the antibiotic against the bacteria.

First claim

What is claimed is:

1 . A method of treating a bacterial infection comprising bacteria that have become resistant to an antibiotic in a subject in need thereof, the method comprising:
administering to the subject a safe and therapeutically effective amount of the antibiotic and a reviving agent selected from the group consisting of glass-ceramic particles, silver ions, and combinations thereof, wherein the reviving agent restores antibiotic activity to the antibiotic against the bacteria.

2 . The method according to claim 1 , wherein the bacteria comprise methicillin-resistant Staphylococcus aureus (MRSA).

3 . The method according to claim 1 , wherein the antibiotic is selected from the group consisting of penicillin, oxacillin, methicillin, nafcillin, cloxacillin, diclosacillin, flucloxacillin, ampicillin, amoxicillin, pivampicillin, hetacillin, bacampicillin, metampicillin, talampicillin, epicillin, carbenicillin, ticarcillin, temocillin, mezlocillin, piperacillin, azlocillin, fosfomycin, vancomycin, daptomycin, gentamicin, ciprofloxacin, and combinations thereof.

4 . The method according to claim 1 , wherein the reviving agent is the glass-ceramic particles,
wherein the glass-ceramic microparticles are synthesized from SiO 2 , CaO, P 2 O 5 , Al 2 O 3 , Na 2 O, and K 2 O, and are glass-ceramic microparticles having a diameter of greater than or equal to about 500 nm to less than or equal to about 100 μm or glass-ceramic nanoparticles having a diameter of greater than or equal to about 0.75 nm to less than or equal to about 100 nm, or a combination thereof.

5 . The method according to claim 1 , wherein the reviving agent is silver (Ag)-doped glass-ceramic particles,
wherein the glass-ceramic microparticles are synthesized from SiO 2 , CaO, P 2 O 5 , Al 2 O 3 , Na 2 O, K 2 O, and Ag 2 O, and are Ag-doped glass-ceramic microparticles having a diameter of greater than or equal to about 500 nm to less than or equal to about 100 μm or Ag-doped glass-ceramic nanoparticles having a diameter of greater than or equal to about 0.75 nm to less than or equal to about 100 nm, or a combination thereof.

6 . The method according to claim 5 , wherein the Ag-doped glass-ceramic microparticles or the Ag-doped glass-ceramic nanoparticles also regenerate bone tissue in the subject.

7 . A bioactive glass-ceramic scaffold comprising:
an interconnected web of struts that define a three dimensional porous structure, the struts comprising a glass-ceramic material system synthesized from SiO 2 , CaO, P 2 O 5 , Al 2 O 3 , Na 2 O, K 2 O, and optionally Ag 2 O, wherein the bioactive glass-ceramic scaffold has antibiotic activity, and wherein the bioactive glass-ceramic scaffold promotes proliferation and differentiation of cells that are in contact with the bioactive glass-ceramic scaffold.

8 . The bioactive glass-ceramic scaffold according to claim 7 , wherein the bioactive glass-ceramic scaffold has as porosity of greater than or equal to about 60% to less than or equal to about 99% and an average pore size of greater than or equal to about 250 μm to less than or equal to about 750 μm.

9 . A method of fabricating the bioactive glass-ceramic scaffold according to claim 7 , the method comprising:
preparing a bioactive glass solution comprising water and:
greater than or equal to about 50 wt. % to less than or equal to about 70 wt. % SiO 2 ,
greater than or equal to about 25 wt. % to less than or equal to about 40 wt. % CaO, and
greater than or equal to about 5 wt. % to less than or equal to about 15 wt. % P 2 O 5 ;
preparing a sol-gel porcelain solution comprising water and:
greater than or equal to about 50 wt. % to less than or equal to about 70 wt. % SiO 2 ,
greater than or equal to about 1 wt. % to less than or equal to about 10 wt. % CaO,
greater than or equal to about 1 wt. % to less than or equal to about 15 wt. % P 2 O 5 ,
greater than or equal to about 10 wt. % to less than or equal to about 20 wt. % Al 2 O 3 ,
greater than or equal to about 0 wt. % to less than or equal to about 15 wt. % Na 2 O,
greater than or equal to about 0 wt. % to less than or equal to about 15 wt. % K 2 O, and
greater than or equal to about 0 wt. % to less than or equal to about 10 wt. % Ag 2 O;
combining the bioactive glass solution and the sol-gel porcelain solution to form a composite solution; submerging a porous foam having a predetermined three-dimensional shape into the composite solution; drying the composite solution in the porous foam to generate a coated foam; burning out the coated foam to form a scaffold precursor; and sintering the scaffold precursor to form the bioactive glass-ceramic scaffold, the bioactive glass-ceramic scaffold having a three-dimensional shape.

10 . A method of fabricating the bioactive glass-ceramic scaffold according to claim 7 , the method comprising:
obtaining glass-ceramic microparticles particles comprising crystalline and amorphous phases, the glass-ceramic microparticles optionally doped with silver (Ag); preparing a polymer slurry by combining and mixing water, a polymer, and the glass-ceramic microparticles particles; submerging a porous foam having a predetermined three-dimensional shape into the composite solution; drying the composite solution in the porous foam to generate a coated foam; burning out the coated foam to form a scaffold precursor; and sintering the scaffold precursor to form the bioactive glass-ceramic scaffold.

11 . A method of fabricating the bioactive glass-ceramic scaffold according to claim 7 , the method comprising:
generating a computer model of a scaffold having a predetermined three-dimensional (3D) structure; obtaining glass-ceramic microparticles particles comprising crystalline and amorphous phases, the glass-ceramic microparticles optionally doped with silver (Ag); adding the glass-ceramic microparticles particles into a binder system comprising a polyolefin, an elastomer, and a fatty acid, introducing the binder system to an extruder and mixing the glass-ceramic microparticles particles, the polyolefin, and the elastomer in the extruding to form a binder system comprising microparticles; extruding the binder system as a filament; and 3D printing the computer model from the filament to form the bioactive glass-ceramic scaffold.

12 . The method according to claim 11 , wherein the polyolefin is selected from the group consisting of poly(methyl methacrylate) (PMMA), polyethylene, polypropylene, acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polylactic acid (PLA), PC/ABS, polyethylene terephthalate (PET), polyphenylsulfone (PPSF), polystyrene, polyether ether ketone (PEEK), polytetrafluoroethylene (PTFE), and combinations thereof; the elastomer is selected from the group consisting of thermoplastic polyurethanes (TPU), ethylene propylene diene monomer (EPDM), thermoplastic polyolefin (TPO), and combinations thereof; and the fatty is a saturated fatty acid, an unsaturated fatty acid, or a combination thereof.

13 . A method of treating a subject having or at risk of having a bacterial infection, the method comprising:
implanting the bioactive glass-ceramic scaffold according to claim 7 in the subject at a location of the bacterial infection or at a location at risk of developing the bacterial infection.

14 . The method according to claim 13 , wherein the bioactive glass-ceramic scaffold is doped with silver.

15 . The method according to claim 14 , wherein the bioactive glass ceramic scaffold releases a safe and therapeutically effective amount of silver ions over a time period of from about 10 day

Assignees

• Univ Michigan State

Inventors

• Chatzistavrou Xanthippi
• Hammer Neal D
• Roch Aljoscha

Classifications

• A61L2400/08

  Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution · CPC title

• A61L2300/406

  Antibiotics · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61L27/10

  Ceramics or glasses · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title