POROUS OSTEOIMPLANT

• US 20080069852A1
• Filed: 01/19/2007
• Published: 03/20/2008
• Est. Priority Date: 01/19/2006
• Status: Active Grant

• Current Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Inventors: Bhattacharyya, Subhabrata, Belaney, Ryan, Winterbottom, John, Kaes, David, Shimp, Lawrence
• Granted Patent: US 9,034,356 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00359 Bone or bony tissue
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• 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 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders

Abstract

The invention is directed toward porous composites for application to a bone defect site to promote new bone growth. The inventive porous composites comprise a biocompatible polymer and a plurality of particles of bone-derived material, inorganic material, bone substitute material or composite material. In certain embodiments, the porous composites are prepared using a method that includes a supercritical fluid (e.g., supercritical carbon dioxide) treatment. The invention also discloses methods of using these composites as bone void fillers.

Claims

1. A porous composite comprising:

a plurality of particles comprising a bone-derived material, an inorganic material, a bone substitute material, a composite material, or any combination thereof, and

a biocompatible polymer,

wherein the porous composite comprises at least some pores that result from a supercritical fluid treatment.

2. The porous composite of claim 1, wherein the porous composite has a porosity of at least about 30%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or more than 90%.

3. The porous composite of claim 1, wherein the composite, after implantation, has pores or channels that can support the in-growth of cells.

26. The porous composite of claim 1, wherein the bone-derived material is obtained from a member of the group consisting of autologous bone, allogenic bone, xenogenic bone, and mixtures thereof.

27. The porous composite of claim 1, wherein the bone-derived material is obtained from a member of the group consisting of non-demineralized bone particles, demineralized bone particles, deorganified bone particles, partially demineralized bone particles, anorganic bone particles, and combinations thereof.

30. The porous composite of claim 1, wherein the inorganic material or bone substitute material is selected from the group consisting of aragonite, dahlite, calcite, amorphous calcium carbonate, vaterite, weddellite, whewellite, struvite, urate, ferrihydrite, francolite, monohydrocalcite, magnetite, goethite, dentin, calcium carbonate, calcium sulfate, calcium phosphosilicate, sodium phosphate, calcium aluminate, calcium phosphate, hydroxyapatite, a-tricalcium phosphate, dicalcium phosphate, β

-tricalcium phosphate, tetracalcium phosphate, amorphous calcium phosphate, octacalcium phosphate (OCP), BIOGLASS™

, fluoroapatite, chloroapatite, magnesium-substituted tricalcium phosphate, carbonate hydroxyapatite, and combinations and derivative thereof.

31. The porous composite of claim 1, wherein the composite material comprises one or more of:

inorganic material and a bone-derived material and one or more of bovine serum albumin, collagen, an extracellular matrix component, a synthetic polymer, and a naturally-derived polymer.

34. The porous composite of claim 1, wherein the composite comprises approximately 40-70% particles by weight.

42. The porous composite of claim 1, wherein the biocompatible polymer is selected from the group consisting of poly(L-lactide-co-D,L-lactide), polyglyconate, poly(arylates), poly(anhydrides), poly(hydroxy acids), polyesters, poly(ortho esters), poly(alkylene oxides), polycarbonates, poly(propylene fumarates), poly(propylene glycol-co fumaric acid), poly(caprolactones), polyamides, polyesters, polyethers, polyureas, polyamines, polyamino acids, polyacetals, poly(orthoesters), poly(pyrolic acid), poly(glaxanone), poly(phosphazenes), poly(organophosphazene), polylactides, polyglycolides, poly(dioxanones), polyhydroxybutyrate, polyhydroxyvalyrate, polyhydroxy-butyrate/valerate copolymers, poly(vinyl pyrrolidone), polycyanoacrylates, poly-urethanes, and polysaccharides.

43. The porous composite of claim 1, wherein the biocompatible polymer comprises poly(caprolactone).

44. The porous composite of claim 1, wherein the biocompatible polymer comprises poly(lactide), poly(glycolide), poly(lactide-co-glycolide), and/or combination thereof.

54. The porous composite of claim 1, wherein the biocompatible polymer is resorbed within approximately 1 month to approximately 3 years.

56. The porous composite of claim 1, wherein the composite further comprises a lubricant agent.

61. The porous composite of claim 1, wherein the composite further comprises a plasticizer.

62. The porous composite of claim 61, wherein the plasticizer is selected from the group consisting of bis(2-ethylhexyl)adipate (DOA), dimethyl adipate (DMAD), monomethyl adipate (MMAD), dioctyl adipate (DOA, bibutyl maleate (DBM), diisobutylmaleate (DIBM), dibutyl sebacate (DBS), triethyl citrate (TEC), acetyl triethyl citrate (ATEC), tributyl citrate (TBC), acetyl tributyl citrate (ATBC), trioctyl citrate (TOC), acetyl trioctyl citrate (ATOC), trihexyl citrate (THC), acetyl trihexyl citrate (ATHC), butyryl trihexyl citrate (BTHC), trimethylcitrate (TMC), N-methyl phthalate, bis(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), bis(n-butyl)phthalate (DBP), butyl benzyl phthalate (BBzP), diisodecyl phthalate (DOP), diethyl phthalate (DEP), diisobutyl phthalate (DIBP), di-n-hexyl phthalate, glycerol, triethylene glycol, sorbitol, monacetin, diacetin, trimethyl trimellitate (TMTM), tri-(2-ethylhexyl) trimellitate (TEHTM-MG), tri-(n-octyl,n-decyl) trimellitate (ATM), tri-(heptyl,nonyl) trimellitate (LTM), n-octyl trimellitate (OTM), benzoates, epoxidized vegetable oils, sulfonamides, N-ethyl toluene sulfonamide (ETSA), N-(2-hydroxypropyl)benzene sulfonamide (HP BSA), N-(n-butyl) butyl sulfonamide (BBSA-NBBS), organophosphates, tricresyl phosphate (TCP), tributyl phosphate (TBP), triethylene glycol dihexanoate, tetraethylene glycol diheptanoate, and polymeric plasticizers.

67. The porous composite of claim 1, wherein the composite further comprises a porogen.

68. The porous composite of claim 67, whereby the porogen dissolves and/or degrades after implantation of the composite leaving a pore.

89. The porous composite of claim 1 further comprising a bioactive agent.

90. The porous composite of claim 89, wherein the bioactive agent is selected from the group consisting of antiviral agent, antimicrobial agent, antibiotic agent, amino acid, peptide, protein, glycoprotein, lipoprotein, antibody, steroidal compound, antibiotic, antimycotic, cytokine, vitamin, carbohydrate, lipid, extracellular matrix, extracellular matrix component, chemotherapeutic agent, cytotoxic agent, growth factor, anti-rejection agent, analgesic, anti-inflammatory agent, viral vector, protein synthesis co-factor, hormone, endocrine tissue, synthesizer, enzyme, polymer-cell scaffolding agent with parenchymal cells, angiogenic drug, collagen lattice, antigenic agent, cytoskeletal agent, mesenchymal stem cells, bone digester, antitumor agent, cellular attractant, fibronectin, growth hormone cellular attachment agent, immunosuppressant, nucleic acid, surface active agent, hydroxyapatite, and penetration enhancer, anti-inflammatory agents, growth factors, angiogenic factors, antibiotics, analgesics, chemotactic factors, bone morphogenic protein, and cytokines.

102. The porous composite of claim 1 further comprising a pharmaceutically acceptable excipient.

103. The porous composite of claim 1, characterized in that the composite has a shape selected from the group consisting of morsels, cylinder, block, wedge, and sheet.

105. An osteoimplant comprising the porous composite of claim 1.

107. A method of preparing a porous composite of claim 1, the method comprising steps of:

providing a plurality of particles comprising a bone-derived material, an inorganic material, a bone substitute material, a composite material, or any combination thereof;

providing a biocompatible polymer;

mixing the particles and biocompatible polymer to obtain a mixture; and

submitting the mixture to a supercritical fluid treatment to obtain the porous composite.

123. A method of treating a bone in a subject, the method comprising administering the porous composite of claim 1 to a subject in need thereof.

4-25. -25. (canceled)

28-29. -29. (canceled)

32. (canceled)

33. (canceled)

35-41. -41. (canceled)

45-53. -53. (canceled)

55. (canceled)

57-60. -60. (canceled)

63-66. -66. (canceled)

69-88. -88. (canceled)

91-101. -101. (canceled)

104. (canceled)

106. (canceled)

108-122. -122. (canceled)

124-134. -134. (canceled)

135. A porous composite comprising:

a plurality of particles comprising a bone-derived material, an inorganic material, a bone substitute material, a composite material, or any combination thereof; and

a biocompatible polymer, wherein the porous composite has a density of between about 1.6 g/cm³ and about 0.05 g/cm³.

136-231. -231. (canceled)