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Ceramic particle group comprising sintered particles of hydroxyapatite 実績あり

外国特許コード F110005389
整理番号 K02014US2
掲載日 2011年9月5日
出願国 アメリカ合衆国
出願番号 65968810
公報番号 20100173158
公報番号 8153255
出願日 平成22年3月17日(2010.3.17)
公報発行日 平成22年7月8日(2010.7.8)
公報発行日 平成24年4月10日(2012.4.10)
国際出願番号 JP2005016837
国際公開番号 WO2006030782
国際出願日 平成17年9月13日(2005.9.13)
国際公開日 平成18年3月23日(2006.3.23)
優先権データ
  • 特願2004-267404 (2004.9.14) JP
  • 特願2005-041348 (2005.2.17) JP
  • 11/662,629 (2007.3.13) US
  • 2005JP016837 (2005.9.13) WO
発明の名称 (英語) Ceramic particle group comprising sintered particles of hydroxyapatite 実績あり
発明の概要(英語) A ceramic particle group dispersed in a solvent in a state of primary particles of single crystal, a method for production thereof and a use thereof are disclosed.
In one embodiment a method is disclosed for producing a sintered particle (ceramic particle) group of hydroxyapatite (HAp), which includes a step of subjecting a system wherein calcium carbonate is present between primary particles of hydroxyapatite (HAp) to sintering and then dissolving calcium carbonate with water to remove calcium carbonate.
A hydroxyapatite (HAp) sintered particle group produced by the above method is a nanometer size particle group having a particle diameter of about 70 to about 120 nm, and is a particle group having a uniform particle diameter (coefficient of variation: 12%), and further 96% of the particle group is dispersed as a single crystal particle.
従来技術、競合技術の概要(英語) BACKGROUND ART
Due to good biocompatibility, calcium phosphates (hereinafter, referred to as "CaP"), as represented by hydroxyapatite (hereinafter, referred to as "HAp"), are of great interest as biomaterials.
For example, calcium phosphates (CaP), and hydroxyapatite (HAp) in particular, have been used as artificial joints, bone fillers, artificial bones, dental implants, percutaneous devices, and dental filler cements.
Further, in order to render bioactivity to a high-molecular medical material such as silicone rubber and polyurethane, calcium phosphate (CaP) such as hydroxyapatite (HAp) is often bonded to such a high-molecular medical material.
Other uses include a filler for chromatography.
When using hydroxyapatite (HAp) or other types of calcium phosphates (CaP) by bonding it to medical material or high-molecular medical material, or when using hydroxyapatite (HAp) or calcium phosphate (CaP) as a filler for chromatography, it is preferable that these materials be used in sintered form, i.e., in the form of ceramic, in order to improve stability and ensure formability in the body.
Further, for uniform coating of the high-molecular medical material and improved resolution in chromatography, a small and uniform particle diameter (narrow particle size distribution) is needed.
Common methods of producing particles of hydroxyapatite (HAp) and other types of calcium phosphates (CaP) include a wet method, a hydrothermal method, and a dry method, for example.
The wet method is predominant in industrial settings since it allows for mass synthesis.
Specific examples of the wet method are described, for example, in Non-Patent Publication 1, which teaches a precipitation method in which phosphoric acid is dropped into a slurry of calcium hydroxide to produce calcium phosphate, and a hydrolysis method in which calcium phosphate is produced by the reaction of calcium phosphate dihydrate with calcium carbonate.
There is also a method in which particles of calcium phosphate (Cap) is dried to produce sintered particles (ceramic particles).
This can be carried out by heating at 800 deg. C. to 1200 deg. C., or by a spray drying method, for example, as disclosed in Non-Patent Publications 2 and 3.
The spray drying method is a technique in which a dispersion of particles, such as a solution or suspension (slurry, etc.) containing effective substance is atomized and the particles are instantly solidified by bringing it into contact with a stream of hot air.
More specifically, a solution or suspension containing primary particles of calcium phosphate (CaP) is sprayed in a stream of hot air to form fine spherical particles of calcium phosphate.
Non-Patent Publication 4 describes a method in which a source solution containing calcium phosphate is dropped into liquid nitrogen to prepare particles of calcium phosphate, which are then sintered to produce sintered particles of calcium phosphate.
This publication also describes sintered particles of calcium phosphate, obtained by this method, whose particle diameter ranges from 450 mu m to 3000 mu m.
Non-Patent Publication 5 describes a method in which a drip-casting process is used to prepare hydroxyapatite particles, which are then sintered to produce sintered particles of hydroxyapatite.
This publication also describes sintered particles of hydroxyapatite, obtained by this method, whose particle diameter ranges from 0.7 mm to 4 mm.
[Non-Patent Publication 1]
Inorganic Materials, Vol 2 No. 258, 393-400 (1995), Controlling Morphology of Crystals and Crystal Groups of Hydroxyapatite and Related Phosphates, Nobuyuki Matsuda, Jo Wakana, Fumihiro Kaji
[Non-Patent Publication 2]
P. Luo and T. G. Nieh Biomaterials, 17, 1959 (1996), Preparing hydroxyapatite powders with controlled morphology
[Non-Patent Publication 3]
L. J. Cummings, P. Tunon, T. Ogawa, Spec.
Publ. R. Soc. Chem. 158, 134 (1994), Macro-Prep Ceramic Hydroxyapatite -- New Life for an Old Chromatographic Technique
[Non-Patent Publication 4]
Biomaterials 1994, Vol. 15 No. 6, M. Fabbri, G. C. Celotti and A. Ravaglioli, Granulates based on calcium phosphate with controlled morphology and porosity for medical applications: physico-chemical parameters and production technique
[Non-Patent Publication 5]
Biomaterials 1996, Vol. 17 No. 20, Dean-Mo Liu, Fabrication and characterization of porous hydroxyapatite granules
The inventors of the present invention have been conducting a study on the synthesis of a chemically bonded hydroxyapatite (HAp)-polymer complex, intended for the development of biocompatible devices for use in bio-tissues, and subcutaneous cells and other soft tissues in particular.
In this connection, the inventors have produced monocrystalline hydroxyapatite particles (ceramic particles) by sintering (pre-baking) at 800 deg. C. This was intended to improve crystallinity of the hydroxyapatite (HAp) for the purpose of suppressing the particles from dissolving and decomposing in the body.
In order for the hydroxyapatite (HAp) particles to form strong chemical bonds on the surface of the high-molecular substrate, the particles need to be well dispersed in the medium when adsorbed by the high-molecular substrate.
A problem, however, is that the hydroxyapatite (HAp) particles (primary particles) fuse together during the sintering process to form irregular secondary particles.
This has resulted in lower dispersibility and a reduced specific surface area.
The problem of irregular secondary particles, lower dispersibility and reduced specific surface area also occurs in the method (spray drying method) disclosed in, for example, Non-Patent Publications 2 and 3.
Further, with the spray drying method, the particle diameter of the calcium phosphate (CaP) particles cannot be controlled to a uniform size (particle size distribution cannot be narrowed beyond a certain range).
To describe more specifically, in the spray drying method, a solution or suspension of particles is atomized in a stream of hot air, and this causes the fine particles (primary particles) of calcium phosphate (CaP) to fuse together and form secondary particles.
Since it is impossible to control the number of fine particles (primary particles) that cluster together in the stream of hot air, it is not possible with the spray drying method to accurately control the particle size distribution of calcium phosphate (CaP) particles.
Thus, when the spray drying method is used to produce ceramic particles of calcium phosphate (CaP), the resulting particles need to be further classified depending on intended use.
For example, in the case where the ceramic particles of calcium phosphate (CaP) are used as a filler for chromatography, the support needs to have a uniform particle diameter (narrow particle size distribution) for improved resolution.
Thus, when using ceramic particles of calcium phosphate (CaP) as a filler for chromatography, a ceramic particle group of calcium phosphate (CaP) needs to be used that has a uniform particle diameter (narrow particle size distribution).
Further, with the producing method of a ceramic particle group of calcium phosphate as disclosed in, for example, Non-Patent Publications 2 and 3, the resulting particle group cannot have a particle diameter smaller than 1 to 8 mu m (Non-Patent Publication 2).
Further, obtaining a particle group of a narrow particle size distribution by classifying the ceramic particle group of calcium phosphate disclosed in Non-Patent Publication 2 is not feasible due to physical limitations.
Indeed, it is very difficult to reduce the particle size distribution any further and classification requires large cost.
The present invention was made in view of the foregoing problems, and an object of the invention is to provide a ceramic particle group that is dispersed in a solvent as primary particles of single crystal, and particularly a calcium phosphate (CaP) sintered particle group (ceramic particle group), as represented by monocrystalline hydroxyapatite (HAp), that is biocompatible, connective and adherent to biological tissues, and that is not easily decomposed and absorbed in the body, and that is useful as medical materials.
The invention also provides to a producing method of such a particle group, and use thereof.

特許請求の範囲(英語) [claim1]
1. A ceramic particle group comprised of granular ceramic particles: wherein a majority of the ceramic particles in the ceramic particle group are monocrystalline primary particles, which are either primary particles of single crystal, or a cluster of primary particles of single crystal that are held together by ionic interactions;
wherein a proportion of the monocrystalline primary particles contained in the ceramic particle group is no less than 70%;
wherein the ceramic particles have a particle diameter in a range of 10 nm to 700 nm;
wherein a coefficient of variation of particle diameter of the ceramic particle group is no greater than 20%; and
wherein the ceramic particles comprise sintered particles of hydroxyapatite.
[claim2]
2. A chromatography filler, which comprises a ceramic particle group of claim 1.
[claim3]
3. A dental or medical material, which comprises a ceramic particle group of claim 1.
[claim4]
4. A cosmetic additive which comprises a ceramic particle group of claim 1.
[claim5]
5. A building material, which comprises a ceramic particle group of claim 1.
[claim6]
6. An industrial material, which comprises a ceramic particle group of claim 1.
  • 発明者/出願人(英語)
  • FURUZONO TSUTOMU
  • OKADA MASAHIRO
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
国際特許分類(IPC)
米国特許分類/主・副
  • 428/402
  • 423/308
  • 501/1
参考情報 (研究プロジェクト等) PRESTO Nanostructure and Material Property AREA
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