Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Phosphorus or phosphorus compound
Reexamination Certificate
1997-11-24
2001-05-01
Levy, Neil S. (Department: 1616)
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Phosphorus or phosphorus compound
C424S422000, C424S423000, C424S426000, C424S484000, C424S485000, C424S486000, C424S489000, C424S499000, C424S603000, C424S724000, C424S531000, C424S549000, C523S218000, C523S219000, C623S908000, C623S911000, C623S919000, C623S923000
Reexamination Certificate
active
06224913
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to materials comprising silica-based glass or ceramic compositions having been treated to form a microporous calcium-phosphate (Ca—P) surface layer having serum-protein like organic molecules, as defined herein, intermingled throughout and, optionally, other biologically active molecules intermingled throughout and/or adsorbed thereon.
BACKGROUND OF THE INVENTION
In U.S. Pat. No. 5,204,106, issued to Schepers et al., (hereby incorporated by reference) the implantation of bioactive glass granules having the composition: 45% SiO
2
, 24.5% Na
2
O, 24.5% CaO and 6% P
2
O
5
, and a size range of 280-425 &mgr;m in diameter into the jaw of beagle dogs is disclosed. With particles of this size range, internal pouches formed in each of the particles and, subsequently, osteoprogenitor cells differentiated into osteoblasts within the pouches, actively laying down bone tissue. Next, bone tissue proliferated from the excavations, surrounded the particles and connected with bone tissue being formed around neighboring particles. Bone tissue was formed within the particle, without being bridged to the lingual or buccal bone plates. At 3 months, bone had grown throughout the surgical defects treated with glass granules. A similar phenomenon was not observed with particles of a larger size range, i.e., ~480-800 micrometers, or a smaller size range, i.e., ~210-300 micrometers.
Glass granules of narrow size range (300-360 &mgr;m) were used in a clinical trial in humans. Schepers et al., “Bioactive Glass Particles of Narrow Size Range: A New Material for the Repair of Bone Defects,”
Implant Dentistry,
2(3):151-156, 1993, incorporated herein by reference. In this clinical study, 87 patients and 106 maxillo facial defects were treated. At 3 months, the application sites had fully solidified. At six months, no radiological difference between the defect sites and the surrounding bone could be discerned.
It was subsequently discovered that particles in the size range 200-300 micrometers effected the same results if implanted into sites exhibiting a reduced metabolic state, particularly as compared to the maxillo-facial sites. Such sites are found, for example, in the appendicular skeleton, and in certain disease states. U.S. application Ser. No. 08/268,510, hereby incorporated by reference.
The in vivo event which initiates the reactions leading to the formation of bone throughout the defects is an excavation of the particles. The excavation is the result of physico-chemical reactions taking place in the glass, as well as a cell-mediated resorption of the internal reaction layer. Bioactive glass reacts at its surface with the formation of two reaction layers: a silica gel below the surface and a Ca—P rich layer at the surface.
It has now been discovered that differential immersion of other geometric forms of melt- or sol-gel-derived silica-based glass or ceramic in aqueous solutions containing serum-protein like organic molecules, as defined herein, results in a microporous surface layer of Ca—P having the serum-protein like organic molecules intermingled throughout. It is expected that silica-based glass or ceramic so conditioned will have an improved performance in vitro and in vivo, e.g., in relation to cell phenotype expression and attachment of cells in general. Prior treatments did not achieve this surface layer.
SUMMARY OF THE INVENTION
According to the present invention, silica-based glasses or ceramics are conditioned to achieve a microporous Ca—P surface layer having serum-protein like organic molecules, as defined herein, intermingled throughout and, optionally, biologically active molecules intermingled throughout and/or adsorbed thereon.
In one aspect, the present invention relates to a method for modifying the surface of silica-based glasses or ceramics by differential immersion in aqueous solutions containing serum-protein like organic molecules to achieve a microporous Ca—P surface layer having serum-protein like organic molecules intermingled throughout.
In yet another aspect, the present invention relates to a material comprising silica-based glasses or ceramics having a microporous Ca—P surface having serum-protein like organic molecules herein intermingled throughout, prepared by differential immersion of the silica-based glasses or ceramics in aqueous solutions containing serum-protein like organic molecules.
In a further aspect, the present invention relates to a material comprising silica-based glasses or ceramics having a microporous Ca—P surface layer having serum-protein like organic molecules intermingled throughout.
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Ducheyne Paul
Radin Shulamith
Levy Neil S.
The Trustees of the University of Pennsylvania
Woodcock Washburn Kurtz Mackiewicz & Norris LLP
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