Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Implantable prosthesis – Bone
Reexamination Certificate
1999-08-09
2001-11-06
Langel, Wayne (Department: 1754)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Implantable prosthesis
Bone
C106S462000, C106S690000, C423S308000, C423S309000, C423S311000
Reexamination Certificate
active
06312468
ABSTRACT:
The present invention relates to a silicon-substituted apatite and to a process for the preparation thereof.
The apatite group of minerals are based on calcium phosphate, with naturally occurring apatite having a molar ratio of Ca/P of 1.67. Hydroxyapatite, which has the chemical formula Ca
10
(PO
4
)
6
(OH)
2
, and hydroxyapatite—glass composites have been used in the recent past as skeletal reconstitution materials and it has been observed that bonding of these bioactive materials to living tissues is achieved through a bone-like apatite layer formed on their surfaces in a body environment. Formation of a bone-like apatite layer on implant material thus plays a vital role in osseointegration of the implant.
K. Hata et al., J. Am. Ceram. Soc., 78, 1049-1053 (1995) have shown that a bone-like apatite layer is formed on the surfaces of CaO and SiO
2
glass-ceramics in simulated body fluid. It is suggested by the authors that the mechanism of formation of the apatite layer comprises the dissolution of calcium and silicate ions from the glass surface which helps the formation of an apatite layer with silicate ions providing nucleation sites. Another mechanism proposed by Hench et al., J. Biomed. Mater. Res., 2, 117, 1971 is that the pH of the surface of the implant becomes alkaline due to dissolution of ions which in turn causes supersaturation resulting in the precipitation of a bone-like apatite layer. Other mechanisms have also been suggested, including the proposal by Li et al., J. Mater. Sci. Mater. Med., 3, 452, 1992, that dissolution of amorphous calcium phosphate from the glass creates a negatively charged surface which attracts calcium ions to the implant surface and finally forms an apatite layer.
Silicate sulphate apatite has been synthesised by a solid state method, K. S. Leshkivich et al., J. Mater. Sci. Mater. Med., 4, 86-94, 1993, and found excellent biocompatability in vivo tests and this material has been suggested for use as a low-load bearing bone graft material.
Silicon has been shown, in small quantities, to have a significant effect on the development and growth of the hard tissue of living bodies.
EP-A-0 540 819 relates to calcium phosphate and calcium carbonate materials with antibacterial properties, in which these materials are used as a carriers for silver and silicon. JP-A-7165518 relates to an antibacterial inorganic powder. JP-A-7008550 relates to a hydroxyapatite material for use in surgical replacement which contains Ba, Bi, Zr, Sr or Si to improve X-ray contrast. JP-A-60024848 relates to a tooth or bone repair composition comprising a mixture of apatite derived from the bones of fish or mammals and an oxide of Zr, Al, Si and Zn.
We have now developed a silicon-substituted apatite material which has a much higher bioactivity than that of pure hydroxyapatite and which may be used as a synthetic bone material.
Accordingly, the present invention provides a synthetic silicon-substituted apatite or hydroxyapatite which comprises from 0.1 to 5% by weight of silicon. By the term silicon-substituted is meant that silicon is substituted into the apatite crystal lattice and is not merely added, in contrast to the prior art. It is believed that the silicon enters the lattice on the phosphate site. The silicon is though to exist and/or substitute as a silicon ion or as a silicate ion.
The silicon-substituted apatite or hydroxyapatite material according to the present invention may be an essentially single phase pure material.
Preferably, the synthetic silicon-substituted apatite or hydroxyapatite comprises from about 0.1 to about 1.6%, more preferably from about 0.5 to about 1.0% by weight of silicon.
The present invention also provides for the preparation of a stoichiometric silicon-substituted apatite which, when heated and optionally sintered at a temperature of from about 500° C. to 1400° C., for example at about 1200° C., produces an essentially single phase material with a crystal structure comparable to pure hydroxyapatite. The present invention therefore allows for the production of an essentially phase pure material of silicon-substituted hydroxyapatite, which contains substantially no impurity phases, such as calcium oxide or tricalcium phosphate (TCP).
The silicon-substituted apatite or hydroxyapatite material may be used as a synthetic bone material, including dental materials, for example for use in bone substitution, implants, fillers and cements, coatings for metallic implants, and for making hydroxyapatite-polymer composites.
In another aspect the present invention provides a process for the preparation of a silicon-substituted apatite, which process comprises reacting a calcium salt or calcium hydroxide with orthophosphoric acid or a salt of orthophosphoric acid in the presence of a silicon-containing compound, the molar ratio of calcium ions to phosphorous-containing ions being from about 1:0.5 to about 1:0.7 and the molar ratio of calcium ions to silicon-containing ions being at least about 1:0.2, whereby a precipitate of a silicon-substituted apatite is formed. Under these conditions it is believed that the silicon-containing compound yields silicon-containing ions, such as silicon ions and/or silicate ions for example, which substitute in the apatite lattice.
The molar ratio of calcium ions to phosphorous ions is preferably from about 1:0.55 to about 1:0.65 and the molar ratio of calcium ions to silicon ions is preferably at least about 1:0.16.
The process of the present invention is advantageously carried out by reacting an aqueous solution comprising a calcium salt or calcium hydroxide and a silicon-containing compound at a pH of from about 9 to about 13 with an aqueous solution comprising a salt of orthophosphoric acid at a pH of from about 9 to about 13. The calcium salt is preferably calcium nitrate and, in particular, calcium nitrate 4-hydrate. The salt of orthophosphoric is preferably diammonium orthophosphate or triammonium orthophosphate. The pH of the aqueous solution of the calcium salt and/or the pH of the aqueous solution of the salt of orthophosphoric acid is preferably adjusted using ammonia, for example concentrated aqueous ammonia. The preferred pH of each solution is about pH 11.
An alternative way of carrying out the process of the present invention comprises reacting an aqueous solution of calcium hydroxide and a silicon-containing compound with an aqueous solution of orthophosphoric acid. The pH of the aqueous solution of calcium hydroxide is preferably from about 10 to about 14, more preferably about 12.3. The pH of the aqueous solution of orthophosphoric acid is preferably from about 1 to about 3, more preferably from about 1 to about 1.5.
In each of the embodiments of the process of the invention the silicon-containing compound preferably comprises a silicon salt, such as a silicon carboxylate. Advantageously the silicon-containing compound comprises silicon acetate and, in particular, silicon acetate 4-hydrate.
The precipitated silicon-substituted apatite may be separated from the reaction mixture by, for example, filtration, and then washed and dried to result in a silicon-substituted apatite material. The dried filter cake material may then be powdered using conventional techniques.
The dried silicon-substituted apatite material may then be heated and optionally sintered using conventional techniques, for example at a temperature of about 1200° C. Upon heating, the silicon-substituted apatite material transforms to a silicon-substituted hydroxyapatite material, although some of the material may decompose to a mixture of hydroxyapatite and calcium oxide or hydroxyapatite and tricalcium phosphate (TCP), depending on the chemical composition of the material. If formed, then preferably substantially all of the TCP is &agr; TCP. Ideally, little or no decomposition of the silicon-substituted apatite material occurs upon heating, thereby resulting in an essentially phase pure material of silicon-substituted hydroxyapatite. A phase purity, as measured by X-ray diffraction, of at least 98% can be achieved, preferably at
Best Serena Michelle
Bonfield William
Gibson Iain Ronald
Jha Lakhan Jee
Santos Jose Domingos Da Silva
Abonetics Limited
Bacon & Thomas
Langel Wayne
LandOfFree
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