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US5565502A
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Isolation of the calcium-phosphate crystals of bone
Assignee: Boston Children's Hospital
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Filing: 1995-03-24
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Granted: 1996-10-15
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Expires: 2015-03-24
Abstract
Abstract The present invention is a process for first removing and isolating the calcium-phosphate crystals of bone from a substantial amount of the organic matrix and cellular constituents of bone without significant physical, chemical or structural alterations in the crystals. The crystals can then be further treated to remove the remaining amount of organic material associated with the crystals, leaving them essentially free of any of the organic constituents of bone, without significant physical, chemical or structural alterations in the crystals.
Inventors
- 👤 Melvin J. Glimcher
- 👤 Hyun-Man Kim
- 👤 Christian Rey
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:47
CPC Classifications
A; A61; A61L; A61L24/00; A61L24/02; A61L27/00; A61L27/02; A61L27/12; A61L27/28; A61L27/30; A61L27/32; A61L27/36; A61L27/3604; A61L27/3608; A61L27/3641; A61L27/3645; A61L27/365; A61L27/3683; A61L27/38; A61L27/3839; A61L27/3843; A61L27/3847; B; B82; B82Y; B82Y30/00; C; C01; C01B; C01B25/00; C01B25/16; C01B25/26; C01B25/32; C01F; C01F11/00; C01F11/18; C01F11/185; A61F; A61F2310/00; A61F2310/00005; A61F2310/00179; A61F2310/00293; A61F2310/00389; A61F2310/00592; A61F2310/00796; C01P; C01P2004/00; C01P2004/20; C01P2004/60; C01P2004/62; C01P2004/64
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
49 words
A composition of calcium-phosphate apatite crystals essentially free of hydroxyl groups, and having essentially the same chemical composition, structure, short range order, and index of crystallinity as the calcium-phosphate crystals present in bone, wherein the bone is selected from the group consisting of bone, cartilage, cementum, dentin, and enamel.
Claim 2
Dependent Claim
49 words
A composition of calcium-phosphate apatite crystals essentially free of hydroxyl groups, and having essentially the same chemical composition, structure, short range order, and index of crystallinity as the calcium-phosphate crystals present in bone, wherein the bone is selected from the group consisting of bone, cartilage, cementum, dentin, and enamel.
Claim 3
Dependent Claim
17 words
The composition of claim 1 containing less than 25% of the dry total weight as organic material.
Claim 4
Dependent Claim
15 words
The composition of claim 2 containing less than 1% dry total weight as organic material.
Claim 5
Dependent Claim
38 words
The composition of claim 1 wherein the crystals are irregularly shaped, very thin plates whose average dimensions are approximately 10 to 50 angstroms in thickness, 30 to 150 angstroms in width, and 70 to 600 angstroms in length.
Claim 6
Dependent Claim
18 words
The composition of claim 1 further comprising adhesive or binder to form a calcium-phosphate crystalline cement or paste.
Claim 7
Dependent Claim
14 words
The composition of claim 1 applied to the surfaces of solid materials for implantation.
Claim 8
Dependent Claim
18 words
The composition of claim 1 formed into ceramic blocks for implantation into gaps or areas of bone resorption.
Claim 9
Dependent Claim
37 words
The composition of claim 1, further comprising a biologically active molecule selected from the group consisting of bone morphogenic proteins, cytokines, antibiotics, chemotherapeutic agents, bone marrow cells or bone progenitor cells, and substances that diminish bone resorption.
Claim 10
Dependent Claim
138 words
The composition of claim 1 produced by the steps of (a) grinding in the absence of water at a temperature equivalent to liquid nitrogen clean bone pieces into particles ranging in size up to approximately 200 microns, where the bone is selected from the group consisting of bone, cartilage, cementum, dentin, and enamel; (b) separating the calcium-phosphate crystals in the bone from the collagen fibrils in the bone by sonication of the particles suspended in a non-aqueous solvent which is less polar than methanol for the collagen fibrils but not the crystals at a temperature just above the freezing temperature of the solvent; (c) separating the non-aqueous solvent and collagen fibrils from the calcium phosphate crystals; and (d) removing the remaining organic material from the calcium phosphate crystals in the absence of water to form calcium-phosphate apatite crystals.
Claim 11
Dependent Claim
22 words
The composition of claim 9 wherein the calcium-phosphate apatite crystals contain less than 2% of the total dry weight as organic material.
Claim 12
Dependent Claim
30 words
The composition of claim 10 wherein the remaining organic material is removed by reaction with an inorganic non-aqueous solvent under conditions equivalent to reaction with hydrazine at low temperatures overnight.
Claim 13
Dependent Claim
15 words
The composition of claim 10 wherein the remaining organic material is removed by plasma ashing.
Claim 14
Dependent Claim
12 words
The composition of claim 1 wherein the bone is mature, mineralized bone.
Claim 15
Dependent Claim
25 words
The composition of claim 1 wherein the crystals are derived from a material selected from the group consisting of bone, dentin, enamel, cementum, and cartilage.
Claim 16
Independent Claim
35 words
A method for treating a patient to repair or replace bone comprising administering to a site in need of treatment thereof an effective amount of the composition of any one of claims 1 to 14.
Claim 17
Dependent Claim
19 words
The method of claim 15 wherein the composition is applied to replace bone lost due to disease or injury.
Claim 18
Independent Claim
22 words
A method for making a prosthetic device comprising forming a substrate of the composition of any one of claims 1 to 14.
Claim 19
Dependent Claim
19 words
The composition of claim 1 wherein the calcium-phosphate apatite crystals are isolated crystals separated from an aggregate of crystals.
References Cited (Backward Citations)
US5167961A
Cited
JPH0297409A
Cited
JPH03109210A
Cited
US5425769A
Cited
JPH04198007A
Cited
JPH04288770A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-10-15 | 2000-04-15 | 2000-10-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-10-15 | 2004-04-15 | 2004-10-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-10-15 | 2008-04-15 | 2008-10-15 | $7700.00 | Window Closed / Lapsed |