JP5224231B2 - Concentric functionally graded material for living body - Google Patents

Concentric functionally graded material for living body Download PDF

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JP5224231B2
JP5224231B2 JP2007154611A JP2007154611A JP5224231B2 JP 5224231 B2 JP5224231 B2 JP 5224231B2 JP 2007154611 A JP2007154611 A JP 2007154611A JP 2007154611 A JP2007154611 A JP 2007154611A JP 5224231 B2 JP5224231 B2 JP 5224231B2
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康公 深瀬
道治 岡野
裕 出井
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本発明は、直径方向に中心部、中間層および表層部からなる生体用同心円状傾斜機能材料であって、骨補填材、人工歯根、歯科用セメント等の生体材料として応用される、機械的強度に優れ且つ生体適合性に優れ新生骨再構築等に有効な生体用同心円状傾斜機能材料に関する。   The present invention is a concentric functionally graded material for living body composed of a central portion, an intermediate layer and a surface layer portion in the diameter direction, and is applied as a biological material such as a bone filling material, artificial tooth root, dental cement, etc. The present invention relates to a concentric functional gradient material for a living body that is excellent in biocompatibility and effective in reconstructing new bone.

顎口腔外科領域では、外傷や顎骨に生ずる腫瘍・嚢胞摘出などの外科的手術によって骨欠損が生じることが多い。また、インプラント治療や義歯製作時においては、歯槽骨の増生、骨移植および骨補填材の埋入が必要な症例も多々認められる。これらの補填・再建に用いられる移植材としては、一般に骨の生着が良好で確実かつ安全であるところから新鮮自家骨が最も多く使用されている。しかし、新鮮自家骨移植材は、原病巣の手術に加え、移植骨採取のために新たな外科的侵襲が加わること、骨組織の供給量と形態にも制限があることが欠点とされた。
以上のことから，自家骨移植に変わる生体材料の開発が行われてきた。W.R.Brownら（特許文献１）は、リン酸カルシウムからなる自己硬化型のセメント(Calcium Phosphate Cement、以下ＣＰＣ）を開発し、Fukaseら（非特許文献１、非特許文献２、非特許文献３、非特許文献４、非特許文献５および非特許文献６）は、このセメントに改良を加え、硬化反応と物性を向上させたと報告している。 In the field of oral and maxillofacial surgery, bone defects are often caused by surgical operations such as trauma and removal of tumors and cysts in the jawbone. In many cases, alveolar bone augmentation, bone grafting, and bone prosthesis placement are required during implant treatment and denture production. In general, fresh autologous bone is most often used as a transplant material used for these supplements and reconstructions because it is favorable for bone engraftment, reliable and safe. However, fresh autologous bone grafting materials have disadvantages in that, in addition to the operation of the original lesion, new surgical invasion is added for harvesting the transplanted bone, and the amount and form of bone tissue are limited.
For these reasons, biomaterials that can be used instead of autologous bone grafts have been developed. WRBrown et al. (Patent Document 1) developed a self-curing cement (Calcium Phosphate Cement, hereinafter referred to as CPC) made of calcium phosphate, and Fukase et al. (Non-Patent Document 1, Non-Patent Document 2, Non-Patent Document 3, Non-Patent Document). 4, Non-Patent Document 5 and Non-Patent Document 6) report that this cement was improved to improve the curing reaction and physical properties.

しかし、このセメント状の骨補填材料は、硬化するまでペース状であるために充填の自由度があるものの硬化するまでの間（３８℃、２４時間）強度を確保できないため、体幹骨のように強度の要求される部位への補強の目的では、制限が生じる。そのため、ブロック状の骨補填材が有用であるが、従来からあるハイドロキシアパタイト（ＨＡｐ）の緻密体または多孔体では、強度は確保されるが生体親和性に優れているために骨の反応性が乏しく、自家骨への置換が望みにくい。骨の反応性を求める場合、第三リン酸カルシウム（β−ＴＣＰ）などの溶解性の高いリン酸カルシウムを用いることが有効であるが、β−ＴＣＰはＨＡｐと比較すると機械的強度が劣ってしまうため、強度と反応性の両方を満足させる材料はなかった。
実際の骨は、外側が緻密骨でシェル構造をなして強度を発揮し、内部は骨髄組織によって生体反応性をしめす特徴を有している。このような機械的強度と生体反応性の両方を満足させるような人工材料の開発が臨まれていた。 However, this cement-like bone grafting material is paced until it hardens, so there is a degree of freedom of filling, but it cannot secure strength until it hardens (38 ° C, 24 hours). However, there is a limitation for the purpose of reinforcing the parts where the strength is required. Therefore, a block-shaped bone grafting material is useful, but the conventional hydroxyapatite (HAp) dense body or porous body can ensure the strength but has excellent biocompatibility, so that the reactivity of the bone is high. It is scarce and it is hard to hope for replacement with autologous bone. When determining bone reactivity, it is effective to use highly soluble calcium phosphate such as tricalcium phosphate (β-TCP), but β-TCP is inferior in mechanical strength compared to HAp. There was no material that satisfies both the reactivity and the reactivity.
The actual bone has a feature that the outer side is a dense bone and forms a shell structure to exert strength, and the inside has a characteristic of bioreactivity by bone marrow tissue. Development of an artificial material that satisfies both such mechanical strength and bioreactivity has been underway.

そこで、生体適合性に優れたＨＡｐと、機械的強度に優れたチタンとを用いて、ＨＡｐとチタンとを含む混合層とチタン層とが同心円状に配置され、放電プラズマ法によって作製された複合焼結材料（例えば、特許文献２参照）や、チタンを中心材にリン酸カルシウムを周辺材とし、チタンとリン酸カルシウム間の中間層において傾斜的に両者の組成が変化し、９０％以上の相対密度を有する３層構造を有し、放電プラズマ法によって作製された生体用複合焼結材料（例えば、特許文献３参照）が提案されている。
しかし、これらの複合焼結材料は、焼結時に生じる熱膨張率の差によって割れが生じやすいという問題がある。また、実際に、骨補填材、人工歯根などとして生体に適用した場合に、生体適合性に優れ新生骨再構築に有効なものかどうか不明であった。
米国特許第４，５１８，４３０号公報 特開２０００−１２８６５１号公報 特開２００１−２５９０１７号公報 Y.Fukase et al., J Dent Res 1990 ; 69(12) : 1852-1856 深瀬康公、日大歯学１９９０；６４：１９０−２０３ 小川勝、日大歯学１９９５；６９：５６１−５７０ 上原浩之、日大歯学１９９５；６９：７２８−７４４ Y.Fukase et al., J Oral Sci 1998 ; 40(2) : 71-76. 和田幸子、日大歯学１９９８；７２：４０８−４２０． Therefore, using HAp having excellent biocompatibility and titanium having excellent mechanical strength, a mixed layer containing HAp and titanium and a titanium layer are arranged concentrically and are produced by a discharge plasma method. Sintered material (see, for example, Patent Document 2) or titanium as a central material and calcium phosphate as a peripheral material, the composition of both changes in a gradient in an intermediate layer between titanium and calcium phosphate, and has a relative density of 90% or more A composite sintered material for living bodies having a three-layer structure and produced by a discharge plasma method has been proposed (for example, see Patent Document 3).
However, these composite sintered materials have a problem that cracks are likely to occur due to a difference in thermal expansion coefficient generated during sintering. In addition, when it is actually applied to a living body as a bone filling material, an artificial tooth root or the like, it is unclear whether it is excellent in biocompatibility and effective for reconstructing new bone.
U.S. Pat. No. 4,518,430 JP 2000-128651 A JP 2001-259017 A Y. Fukase et al., J Dent Res 1990; 69 (12): 1852-1856 Yasuhiko Fukase, Nihon University Dentistry 1990; 64: 190-203 Masaru Ogawa, Nihon University Dentistry 1995; 69: 561-570 Uehara Hiroyuki, Nihon University Dentistry 1995; 69: 728-744 Y. Fukase et al., J Oral Sci 1998; 40 (2): 71-76. Wada Sachiko, Nihon University Dentistry 1998; 72: 408-420.

従って、本発明の課題は、実際の骨と同様の機械的強度と生体反応性の両方を満足させるような生体用人工材料を提供することにある。   Accordingly, an object of the present invention is to provide a biomaterial that satisfies both mechanical strength and bioreactivity similar to those of actual bone.

本発明者らは、放電プラズマ焼結法（ＳＰＳ法）により、機械的強度と生体反応性の両方を兼ね備えた傾斜機能材料を得ることを目的として鋭意研究した結果、ＨＡｐ等の生体適合性の高い材料とチタン等の機械的強度の高い材料とを、円筒状仕切体を利用して、円柱状に複合化させ、かつ、両者の中間層として生体適合性の高い材料と機械的強度の高い材料との混合割合が段階的に異なる３層以上の組成傾斜層を介在させて作成した成形体を放電プラズマ焼結法により焼結して生体用同心円状傾斜機能材料とすることで、機械的性質、靭性に優れ且つ新生骨再構築等に有効な生体用同心円状傾斜機能材料が得られることを見出して本発明を完成した。   As a result of diligent research for the purpose of obtaining a functionally gradient material having both mechanical strength and bioreactivity by the spark plasma sintering method (SPS method), the present inventors have found that biocompatible materials such as HAp have been obtained. A high material and a material with high mechanical strength such as titanium are combined into a columnar shape using a cylindrical partition, and a material with high biocompatibility and high mechanical strength is used as an intermediate layer between them. By forming a molded body made by interposing three or more composition gradient layers with different mixing ratios with the material by a discharge plasma sintering method into a concentric functionally gradient material for a living body, The present invention has been completed by finding that a concentric functionally graded material for living body that is excellent in properties and toughness and is effective for reconstructing new bone can be obtained.

従って、本発明は、以下の（１）から（１１）に関するものである：
（１） 直径方向に中心部、中間層および表層部からなる生体用同心円状傾斜機能材料であって、中心部は機械的強度が高い材料、表層部は生体適合性が高い材料からなり、中間層は、機械的強度が高い材料と生体適合性が高い材料とを混合した層であって、機械的強度が高い材料と生体適合性が高い材料との混合割合が表層に向かって生体適合性が高い材料が多くなる組成傾斜した３層以上からなる、生体用同心円状傾斜機能材料；
（２） 機械的強度が高い材料として、チタンおよびハイドロキシアパタイト（ＨＡｐ）の少なくとも１種を用いる上記（１）の生体用同心円状傾斜機能材料；
（３） 機械的強度が高い材料が、更に第三リン酸カルシウム（ＴＣＰ）を含む上記（２）の生体用同心円状傾斜機能材料；
（４） 生体適合性が高い材料として、ＨＡｐおよびＴＣＰの少なくも１種を用いる上記（１）から（３）のいずれかの生体用同心円状傾斜機能材料；
（５） 機械的強度が高い材料としてチタンを、生体適合性が高い材料として、ＨＡｐまたはＨＡｐとＴＣＰとの混合物を用いる上記（５）の生体用同心円状傾斜機能材料；
（６） 機械的強度が高い材料としてチタンとＨＡｐの混合物を、生体適合性が高い材料として、ＨＡｐを用いる上記（１）の生体用同心円状傾斜機能材料；
（７） 機械的強度が高い材料としてチタンとＴＣＰ混合物を、生体適合性が高い材料として、ＴＣＰを用いる上記（１）の生体用同心円状傾斜機能材料；
（８） 機械的強度が高い材料としてＨＡｐを、生体適合性が高い材料として、ＴＣＰを用いる上記（１）の生体用同心円状傾斜機能材料；
（９） ＴＣＰとして、β−ＴＣＰを用いる上記（２）から（８）のいずれかの生体用同心円状傾斜機能材料；
（１０） チタンとして、水素化チタンを用いる上記（２）から（９）のいずれかの生体用同心円状傾斜機能材料；および
（１１） 機械的強度が高い材料と、生体適合性が高い材料とを円柱状に複合化させ、かつ、両者の中間層として、機械的強度が高い材料と生体適合性が高い材料との混合割合が段階的に異なる３層以上の組成傾斜層を介在させて作製した成形体を放電プラズマ焼結法により焼結して得られる上記（１）から（１０）のいずれかの生体用同心円状傾斜機能材料。 Accordingly, the present invention relates to the following (1) to (11):
(1) A concentric functionally graded material for a living body consisting of a central portion, an intermediate layer and a surface layer portion in the diameter direction, wherein the central portion is made of a material having high mechanical strength, and the surface layer portion is made of a material having high biocompatibility. The layer is a layer in which a material having high mechanical strength and a material having high biocompatibility are mixed, and the mixing ratio of the material having high mechanical strength and the material having high biocompatibility is biocompatible toward the surface layer. Concentric functionally graded material for living body, composed of three or more layers with a composition gradient with an increased amount of high-materials;
(2) The concentric functionally gradient material for living body according to (1) above, wherein at least one of titanium and hydroxyapatite (HAp) is used as the material having high mechanical strength;
(3) The concentric functional gradient material for living body according to (2) above, wherein the material having high mechanical strength further contains tricalcium phosphate (TCP);
(4) The concentric functional gradient material for living body according to any one of (1) to (3) above, wherein at least one of HAp and TCP is used as the material having high biocompatibility;
(5) The concentric functionally gradient material for living body according to the above (5) using titanium as a material having high mechanical strength and HAp or a mixture of HAp and TCP as a material having high biocompatibility;
(6) The concentric functionally gradient material for living body according to (1) above, wherein a mixture of titanium and HAp is used as a material having high mechanical strength, and HAp is used as a material having high biocompatibility;
(7) The bioconcentric concentric functionally gradient material according to the above (1) using a mixture of titanium and TCP as a material having high mechanical strength and TCP as a material having high biocompatibility;
(8) The concentric functionally gradient material for living body according to the above (1) using HAp as a material having high mechanical strength and TCP as a material having high biocompatibility;
(9) The concentric circularly gradient functional material for living body according to any one of (2) to (8) above, wherein β-TCP is used as TCP;
(10) The concentric functionally gradient material for living organisms according to any one of (2) to (9) above, wherein titanium hydride is used as titanium; and (11) a material having high mechanical strength and a material having high biocompatibility. Is made by combining three or more composition graded layers with different mixing ratios of a material having high mechanical strength and a material having high biocompatibility as an intermediate layer. A concentric functionally gradient material for a living body according to any one of (1) to (10), which is obtained by sintering the formed body by a discharge plasma sintering method.

本発明の生体用同心円状傾斜機能材料は、曲げ強度、ヤング率などの機械的強度において優れており、また、骨補填材料として使用した場合に、活発に骨の破壊と新生骨の再構築が起こり、生体反応性においても優れている。従って、本発明の生体用同心円状傾斜機能材料は、骨補填材、人工歯根、歯科用セメント等の生体材料として極めて有用である。   The concentric functionally gradient material for living body of the present invention is excellent in mechanical strength such as bending strength and Young's modulus, and when used as a bone replacement material, it actively destroys bone and reconstructs new bone. Occurs and is also excellent in bioreactivity. Therefore, the biomedical concentric functionally gradient material of the present invention is extremely useful as a biomaterial for bone filling materials, artificial tooth roots, dental cements and the like.

本発明の生体用同心円状傾斜機能材料において、中心部に用いる機械的強度が高い材料としては、チタンおよびハイドロキシアパタイト（ＨＡｐ）の少なくとも１種を用いるのが好ましい。チタンは、生体体液中で金属イオンが溶出することがなく、生体に無害であって、同心円状状傾斜機能材料の中心部に用いることで機械的強度を向上させることができる。チタンとしては、水素化チタン（ＴｉＨ２）が好ましい。水素化チタンは、還元作用があるため、ＨＡｐとの分解反応がなく、得られる焼結体にわれが生じにくいため、本発明においては特に好ましい。実際に用いる際には、チタン粉末の粒度は２０μｍから５０μｍが好ましい。
ＨＡｐは、Ｃａ１０（ＰＯ４）６（ＯＨ）２で表される化合物であり、骨を構成する主成分である。ＨＡｐは骨に吸収されることがないので中心材として使用できる。特に、ＨＡｐは、粒度（二次粒子）が７５μｍから１５０μｍであるものが好ましい。また、粒形は球状のものが好ましい。ＨＡｐとしては、具体的には、例えば、ＳＨＡｐ−１００（粒度：４０μｍ、太平化学工業製、市販のＨＡｐ−１００と同成分のものを球状化したＨＡｐ）などが好ましいものとして挙げられる。
中心部に用いる機械的強度が高い材料として、チタンおよびＨＡｐをそれぞれ単独で用いてもよく、両者の混合物を用いてもよい。混合物として用いる場合には、両者の混合割合としては、体積比で、チタンとＨＡｐとの割合は、１００未満：０超から７５：２５が好ましい。また、これらに、第三酸カルシウム（ＴＣＰ）を添加してもよい。本発明で用いるＴＣＰとは、第三リン酸カルシウム（Ｃａ３（ＰＯ４）２）を指し、その物性、溶解性および生体親和性はＨＡｐに良く似ている。ＴＣＰは生体親和性が高く、生体へ適用した場合に、骨に吸収された消失してしまう性質を持つ。ＴＣＰには結晶構造の違う、高温型のα相（α‐ＴＣＰ）、低温型のβ相（β‐ＴＣＰ）、高温高圧相のγ相（γ−ＴＣＰ）が存在し、生体材料として盛んに使われるのはα相とβ相である。α‐ＴＣＰは水に対する溶解度が高く、加水分解反応によりＨＡｐになる。また、β‐ＴＣＰも水に対する溶解度は比較的高く、生体親和性に優れていることから，生体吸収性のインプラント材として骨充填材などに用いられている。本発明では、α‐ＴＣＰ、β‐ＴＣＰ、γ−ＴＣＰのいずれを用いてもよく、特にβ−ＴＣＰが好ましい。また、β−ＴＣＰの粒度は１μｍから２０μｍであるものが好ましく、球形のものが好ましい。
ＴＣＰは、中心部に用いるチタン、ＨＡｐあるいはそれらの混合物に対して、体積比でＴＣＰとチタン、ＨＡｐあるいはそれらの混合物との割合が０超：１００未満から１５：８５が好ましい。 In the concentric functionally gradient material for living body of the present invention, it is preferable to use at least one of titanium and hydroxyapatite (HAp) as the material having high mechanical strength used for the central portion. Titanium does not elute metal ions in the biological fluid, is harmless to the living body, and can be used for the central part of the concentric functionally gradient material to improve the mechanical strength. Titanium hydride (TiH 2 ) is preferable as titanium. Titanium hydride is particularly preferable in the present invention because it has a reducing action and does not have a decomposition reaction with HAp. When actually used, the particle size of the titanium powder is preferably 20 μm to 50 μm.
HAp is a compound represented by Ca 10 (PO 4 ) 6 (OH) 2 and is a main component constituting bone. Since HAp is not absorbed by bone, it can be used as a central material. In particular, the HAp preferably has a particle size (secondary particle) of 75 μm to 150 μm. The particle shape is preferably spherical. Specific examples of HAp include SHAp-100 (particle size: 40 μm, manufactured by Taihei Chemical Industry, HAp obtained by spheroidizing the same component as commercially available HAp-100).
Titanium and HAp may be used alone or a mixture of both as a material having high mechanical strength used for the central portion. When used as a mixture, the mixing ratio of the two is preferably a volume ratio, and the ratio of titanium and HAp is less than 100: more than 0 to 75:25. Moreover, you may add calcium trioxide (TCP) to these. TCP used in the present invention refers to tricalcium phosphate (Ca 3 (PO 4 ) 2 ), and its physical properties, solubility, and biocompatibility are very similar to HAp. TCP has a high biocompatibility, and when applied to a living body, it has a property of disappearing after being absorbed by bones. TCP has different crystal structures, high temperature type α phase (α-TCP), low temperature type β phase (β-TCP), high temperature high pressure phase γ phase (γ-TCP), and it is prosperous as a biomaterial The α phase and β phase are used. α-TCP has high solubility in water and becomes HAp by hydrolysis reaction. In addition, β-TCP has a relatively high solubility in water and is excellent in biocompatibility. Therefore, β-TCP is used as a bone-absorbing material as a bioabsorbable implant material. In the present invention, any of α-TCP, β-TCP, and γ-TCP may be used, and β-TCP is particularly preferable. Moreover, the particle size of β-TCP is preferably 1 μm to 20 μm, and is preferably spherical.
TCP preferably has a volume ratio of TCP to titanium, HAp or a mixture thereof of more than 0: less than 100 to 15:85 with respect to titanium, HAp or a mixture thereof used in the central portion.

本発明の生体用同心円状傾斜機能材料において、表層部に用いる生体適合性が高い材料として、ＨＡｐおよびＴＣＰの少なくとも１種を用いるのが好ましい。なお、中心部に機械的強度の高い材料として、ＨＡｐを用いた場合には、表層部に用いる生体適合性が高い材料としてＴＣＰを用いるのが好ましい。これらのＨＡｐおよびＴＣＰは上記したものを同様に用いることがきる。表層部には、ＨＡｐおよびＴＣＰのそれぞれを単独で用いてよく、両者の混合物でもよい。混合物として用いる場合には、両者の混合割合としては、体積比で、ＨＡｐとＴＣＰとの割合は、５０：５０から９０：１０が好ましい。
なお、中心部に機械的強度の高い材料として、ＨＡｐを用いた場合には、表層部に用いる生体適合性が高い材料としてＴＣＰを用いるのが好ましい。中心部に用いる機械的強度の高い材料と、表層部に用いる生体適合性の高い材料の組み合せとしては、中心部にチタン、表層部にＨＡｐまたはＨＡｐとＴＣＰの混合物の組み合せ、中心部にチタンとＨＡｐの混合物、表層部にＨＡｐの組み合わせ、中心部にチタンとＴＣＰの混合物、表層部にＴＣＰの組み合わせ、中心部にＨＡｐ、表層部にＴＣＰと組み合わせが好ましい。 In the concentric functionally gradient material for living body of the present invention, it is preferable to use at least one of HAp and TCP as the material having high biocompatibility used for the surface layer portion. In addition, when HAp is used as a material having high mechanical strength in the central portion, it is preferable to use TCP as a material having high biocompatibility used for the surface layer portion. These HAp and TCP can be used in the same manner as described above. In the surface layer portion, each of HAp and TCP may be used alone, or a mixture of both may be used. When used as a mixture, the mixing ratio of the two is preferably a volume ratio, and the ratio of HAp and TCP is preferably 50:50 to 90:10.
In addition, when HAp is used as a material having high mechanical strength in the central portion, it is preferable to use TCP as a material having high biocompatibility used for the surface layer portion. As a combination of a material having high mechanical strength used for the center part and a material having high biocompatibility used for the surface layer part, titanium is used for the center part, HAp or a mixture of HAp and TCP is used for the center part, and titanium is used for the center part. A mixture of HAp, a combination of HAp in the surface layer portion, a mixture of titanium and TCP in the center portion, a combination of TCP in the surface layer portion, a combination of HAp in the center portion and TCP in the surface layer portion is preferable.

本発明の生体用同心円状傾斜機能材料において、中間層は、機械的強度が高い材料と生体適合性が高い材料とを混合した層であって、機械的強度が高い材料と生体適合性が高い材料との混合割合が表層に向かって生体適合性が高い材料が多くなる組成傾斜した３層以上からなる。組成傾斜した中間層が３層未満であると、粉末成形体を放電プラズマ焼結する際に、内部応力により層間剥離や割れが生じ、良好な生体用同心円状傾斜機能焼結体を得ることが困難になるためである。中間層の数としては多いほうが効果的であるが、あまりに多くすると製造が複雑になり好ましくないばかりか、機械的強度の低下を招くこととなる。実用的には同心円状傾斜機能材料の大きさにもよるが最大でも８層程度にするのが通常である。   In the concentric functionally gradient material for living body of the present invention, the intermediate layer is a layer in which a material having high mechanical strength and a material having high biocompatibility are mixed, and the material having high mechanical strength and biocompatibility is high. The mixing ratio with the material is composed of three or more layers with a composition gradient in which the amount of the material having high biocompatibility increases toward the surface layer. When the composition-graded intermediate layer is less than three layers, delamination and cracking occur due to internal stress when the powder compact is sintered by discharge plasma, and a good concentric gradient functional sintered body for living body can be obtained. This is because it becomes difficult. A larger number of intermediate layers is more effective. However, if the number is too large, the production becomes complicated, which is not preferable, and the mechanical strength is lowered. Practically, although it depends on the size of the concentric functionally graded material, it is usually about 8 layers at the maximum.

本発明の生体用同心円状傾斜機能材料の典型的な例を図７に示した。図７の第１層が、機械的強度が高い材料からなる中心部、第５層が、生体適合性が高い材料からなる表層部、第２層から第４層が、機械的強度が高い材料と生体適合性が高い材料との混合割合が表層に向かって生体適合性が高い材料が多くなる組成傾斜した３層に相当する。   A typical example of the concentric functionally gradient material for living body of the present invention is shown in FIG. The first layer in FIG. 7 is a central portion made of a material having high mechanical strength, the fifth layer is a surface layer portion made of a material having high biocompatibility, and the second to fourth layers are materials having high mechanical strength. The mixing ratio of the material having high biocompatibility corresponds to three layers having a composition gradient in which the amount of material having high biocompatibility increases toward the surface layer.

本発明の生体用同心円状傾斜機能材料は、機械的強度が高い材料と、生体適合性が高い材料とを円柱状に複合化させ、かつ、両者の中間層として、機械的強度が高い材料と生体適合性が高い材料との混合割合が段階的に異なる３層以上の組成傾斜層を介在させて作製した成形体を放電プラズマ焼結法により焼結して得られる。
以下、図１〜６に基づいて、中心部がチタン、表層部がハイドロキシアパタイト（ＨＡｐ）でその中間が３層の傾斜組成の中間層からなる全５層の同心円状傾斜機能材料を例に挙げて、本発明の同心円状傾斜機能材料の製造方法について説明する。他の同心円状傾斜機能材料も同様にして製造することができる。 The concentric functionally gradient material for living body according to the present invention is a composite of a material having high mechanical strength and a material having high biocompatibility in a cylindrical shape, and a material having high mechanical strength as an intermediate layer therebetween. It can be obtained by sintering a molded body produced by interposing three or more composition gradient layers having different mixing ratios with a material having high biocompatibility in stages by a discharge plasma sintering method.
Hereinafter, based on FIGS. 1 to 6, an example of all five layers of concentric functionally graded materials having a center portion of titanium, a surface layer portion of hydroxyapatite (HAp), and an intermediate layer of a three-layered gradient composition is taken as an example. The method for producing the concentric functionally gradient material of the present invention will be described. Other concentric functionally gradient materials can be manufactured in the same manner.

粉末成形装置として、支持台、外径の異なる４本の円筒状仕切体、円筒状ダイス及びパンチを準備する。図１は、支持台の構成を示す図で、図１（ａ）は正面断面図で、図２（ｂ）は平面図である。図１に示すように、支持台１は、支持台中央に円筒状ダイス内側に嵌合する円柱状凸起２を備えていて、その凸起２内部には同心円状の階段状凹部３を備えていて、各階段状凹部３のそれぞれの内径は、外径の異なる大きさの円筒状仕切体のそれぞれの外径と略一致する内径となっている。そして、各階段状凹部に各円筒状仕切体を立設できるようになっている。   As a powder forming apparatus, a support base, four cylindrical partitions having different outer diameters, a cylindrical die and a punch are prepared. 1A and 1B are diagrams showing a configuration of a support base, FIG. 1A is a front sectional view, and FIG. 2B is a plan view. As shown in FIG. 1, the support base 1 includes a columnar protrusion 2 that fits inside the cylindrical die at the center of the support base, and includes a concentric stepped recess 3 inside the protrusion 2. And each internal diameter of each step-shaped recessed part 3 is an internal diameter which substantially corresponds with each external diameter of the cylindrical partition body of a magnitude | size from which an external diameter differs. Each cylindrical partition can be erected in each stepped recess.

また、他の変形例としては、図示していないが、支持台は前記した階段状凹部を備えた円柱状凸起に代えて、同心円状の階段状凸起を備えた円柱状凸起にしてもよい。この場合には、同心円状の階段状凸起のそれぞれの外径は、外径の異なる円筒状仕切体の内径とそれぞれ一致するようになっていて、各凸起に円筒状仕切体を嵌合して立設することができる。また、他の変形例としては、図８に示すように、支持台１の上面の円柱状凸起２に複数の円筒状仕切体を嵌入できる同心円状溝４を備えている支持台上の円柱状凸起２であってもよい。同心円状溝４の外径は各円筒状仕切体の外径と一致していて、同心円状溝の幅寸法は各円筒状仕切体の肉厚とほぼ同一又はそれよりやや広い寸法とする。   Further, as another modification, although not shown, the support base is a columnar protrusion having a concentric stepped protrusion instead of the columnar protrusion having the stepped recess described above. Also good. In this case, the outer diameter of each of the concentric stepped protrusions is the same as the inner diameter of the cylindrical partition body having a different outer diameter, and the cylindrical partition body is fitted to each protrusion. Can be erected. As another modification, as shown in FIG. 8, a circle on the support base provided with concentric circular grooves 4 into which a plurality of cylindrical partition bodies can be fitted in the columnar protrusions 2 on the upper surface of the support base 1. It may be a columnar protrusion 2. The outer diameter of the concentric groove 4 coincides with the outer diameter of each cylindrical partition, and the width of the concentric groove is approximately the same as or slightly wider than the thickness of each cylindrical partition.

円柱状凸起２にこれらの同心円状の階段状凹部、同心円状の階段状凸部、或は同心円状溝を設けることで、支持台上においての円筒状仕切体の位置決めを正確にかつ容易に行なうことが可能となる。
支持台の材料については、特に限定されるものではないが、Ａｌ、Ｚｎ、Ｍｇ、Ｆｅ、Ｃｕ及びその合金等の金属材料を用いることができるが、軽量のＡｌ、Ｚｎ、Ｍｇ及びその合金を用いることが好ましい。 By providing these concentric stepped concave portions, concentric stepped convex portions, or concentric grooves in the columnar protrusion 2, the cylindrical partition body can be positioned accurately and easily on the support base. Can be performed.
The material of the support base is not particularly limited, but metal materials such as Al, Zn, Mg, Fe, Cu and alloys thereof can be used, but lightweight Al, Zn, Mg and alloys thereof can be used. It is preferable to use it.

図１に示す円柱状凸起内部に同心円状の階段状凹部を備えた支持台を用いて、中心部がチタンで表層部がＨＡｐからなる生体用同心円状機能傾斜材料を製造する方法について説明する。   A method for producing a concentric functionally graded material for a living body having a center portion made of titanium and a surface layer portion made of HAp will be described using a support base having concentric stepped recesses inside a cylindrical protrusion shown in FIG. .

まず、支持台１の円柱状突起中央凹部５に、図２に示すように、外径の最も小さい第１の円筒状仕切体６を立設する。そして、立設した第１の円筒状仕切体内にチタン粉末７を充填する。
次いで、図３に示すように第１の円筒状仕切体６の外径よりも大きい内径の第２の円筒状仕切体８を支持台１の階段等凹部３に立設し、第１の円筒状仕切体６の外側と第２の円筒状仕切体８の内側とで構成される空間にチタン粉末とＨＡｐ粉末との混合粉末（ａ）９を充填する。次いで、第２の円筒状仕切体８の外径よりも大きい内径の第３の円筒状仕切体１０を支持台１の階段状凹部３に立設し、第２の円筒状仕切体８の外側及び第３の円筒状仕切体１０の内側とで形成される空間に前記混合粉末（ａ）よりもチタン粉末の配合割合比が少ないハイドロキシアパタイト粉末とチタン粉末との混合粉末（ｂ）を充填する。 First, as shown in FIG. 2, the first cylindrical partition 6 having the smallest outer diameter is erected in the columnar protrusion central recess 5 of the support base 1. Then, the titanium powder 7 is filled into the first cylindrical partition that is erected.
Next, as shown in FIG. 3, a second cylindrical partition body 8 having an inner diameter larger than the outer diameter of the first cylindrical partition body 6 is erected in the concave portion 3 such as the staircase of the support base 1, and the first cylinder A mixed powder (a) 9 of titanium powder and HAp powder is filled in a space formed by the outside of the shaped partition 6 and the inside of the second cylindrical partition 8. Next, a third cylindrical partition body 10 having an inner diameter larger than the outer diameter of the second cylindrical partition body 8 is erected in the stepped recess 3 of the support base 1, and the outside of the second cylindrical partition body 8. And a space formed by the inside of the third cylindrical partition 10 is filled with a mixed powder (b) of a hydroxyapatite powder and a titanium powder having a smaller proportion of titanium powder than the mixed powder (a). .

ついで、第３の円筒状仕切体１０の外径よりも大きい内径の第４の円筒状仕切体１１を支持台の階段状凹部に立設し、第３の円筒状仕切体１０の外側と第４の円筒状仕切体１１の内側とで形成される空間に、前記混合粉末（ｂ）よりもチタン粉末の配合割合が少ないＨＡｐ粉末とチタン粉末の混合粉末（ｃ）を充填する。最後に、第４の円筒状仕切体１１の外径よりも大きい内径のグラファイト製ダイス１２を円柱状凸起２に嵌合立設し、ダイス１２内側と第４の円筒状仕切体１１の外側とで形成される空間にＨＡｐ粉末１３を充填する。なお、円柱状のグラファイト製ダイスの内面に離形材としてのカーボンペーパーを設けてあることが好ましい。その後に、４本の円筒状仕切体を引き抜く。引き抜く際には円筒状仕切体を回転させながら引き抜くことで、円筒状仕切体に充填した粉末を付着されることなく、また、充填した粉末層の形状を保った状態とすることができる。これによって、中心部から外表面迄が全５層となり、中心部がチタンで、外表面がＨＡｐで、中間部がチタンＨＡｐの組成傾斜層の全体で５層の粉末成形体が得られる。   Next, a fourth cylindrical partition 11 having an inner diameter larger than the outer diameter of the third cylindrical partition 10 is erected in the stepped recess of the support base, and the third cylindrical partition 10 and the outer side of the third cylindrical partition 10 are 4 is filled with a mixed powder (c) of the HAp powder and the titanium powder having a smaller blending ratio of the titanium powder than the mixed powder (b). Finally, a graphite die 12 having an inner diameter larger than the outer diameter of the fourth cylindrical partition 11 is fitted and erected on the columnar protrusion 2, and the inside of the die 12 and the outer side of the fourth cylindrical partition 11 are set. The space formed by and is filled with the HAp powder 13. In addition, it is preferable that carbon paper as a release material is provided on the inner surface of a cylindrical graphite die. Thereafter, the four cylindrical partitions are pulled out. When pulling out, the cylindrical partition body is pulled out while being rotated, so that the powder filled in the cylindrical partition body is not attached, and the shape of the filled powder layer can be maintained. As a result, a total of 5 layers from the central part to the outer surface, titanium in the central part, HAp in the outer surface, and titanium HAp in the middle part is obtained as a total of 5 layers of powder compacts.

円筒状仕切体を引き抜いた後に、ダイス内の粉末成形体上面に必要に応じて丸く切り抜かれたカーボンペーパーで蓋をして、グラファイト製パンチをダイス内に挿入した後、支持台及び粉末を充填してあるダイスの全体を上下逆転させる。
円筒状仕切体の材質としては、銅、銅合金、ステンレス鋼等の金属材料を用いることが好ましい。円筒状仕切体に金属材料を用いることによって、粉末が付着しにくく、充填及び円筒状仕切体の抜き取りが容易になるとともに、肉厚を薄くしても仕切体としての強度が保てる。ダイスから支持台を取り外し、必要に応じて丸く切り抜かれたカーボンペーパーで蓋をして、その上からもう１つのグラファイト製パンチ１４を挿入し、図５に示すように、ダイス内に充填した粉末がこぼれないようにパンチ１４で蓋をした状態にする。プレス機で上下のグラファイト製パンチに約１０ＭＰａ程度の予備加圧を行いダイス内粉末を圧粉体とする。ついで、図６に示すように、圧粉体１５を内蔵するダイス１２及びパンチ１４を放電プラズマ焼結機の真空室１６内にセットし、電源１７から加圧ラム１８を通じて直流パルス電流をパンチ１４に加えて粉末粒子間の放電現象を利用して焼結を行う。得られた焼結体をダイスより取り出し、焼結体の端面を研磨して図７に示すように全体で第１層１９より第５層２３からなる生体同心円状傾斜機能材料２４とする。 After pulling out the cylindrical partition, cover the upper surface of the powder compact in the die with carbon paper cut out as necessary, insert a graphite punch into the die, and then fill the support base and powder. The whole die is turned upside down.
As a material of the cylindrical partition, it is preferable to use a metal material such as copper, a copper alloy, and stainless steel. By using a metal material for the cylindrical partition, it is difficult for powder to adhere, and filling and extraction of the cylindrical partition are facilitated, and strength as a partition can be maintained even if the wall thickness is reduced. Remove the support from the die, cover it with carbon paper cut out as necessary, insert another graphite punch 14 from above, and fill the die as shown in FIG. Cover with punch 14 to prevent spills. A pre-pressurization of about 10 MPa is performed on the upper and lower graphite punches with a press machine, and the powder in the die is used as a green compact. Next, as shown in FIG. 6, a die 12 containing a green compact 15 and a punch 14 are set in a vacuum chamber 16 of a discharge plasma sintering machine, and a direct current pulse current is applied from a power source 17 through a pressure ram 18 to the punch 14. In addition to the above, sintering is performed by utilizing a discharge phenomenon between powder particles. The obtained sintered body is taken out of the die, and the end face of the sintered body is polished to form a bio-concentric functionally gradient material 24 composed of the first layer 19 to the fifth layer 23 as shown in FIG.

上記説明例では、円筒仕切体を中心部に立設して粉末を充填する手順を中心部から繰り返して複合体の製造を行ったが、中心部から行う代わりに、外周部から粉末を充填、即ち、ダイス内側と第４の円筒状仕切体とで形成される空間に、まず最初に粉末の充填を行い、粉末を充填する手順を中心部に向かって順次繰り返して複合体を製造しても、同等の複合体を製造することができる。
また、他の例としては、支持台上に、最初に径の異なる複数（４本以上）の円筒状仕切体を同心円状に立設し、かつ、最大径の円筒状仕切体の外側に同心円状に円筒状ダイスを立設し、次いで中心の円筒状仕切体内に中心部用粉末（Ａ）を充填し、最大径の円筒状仕切体の外側と円筒状ダイスの内側とで形成される空間に表層部用生体材料粉末（Ｂ）を充填し、複数の円筒状仕切体間で形成されるそれぞれの空間には、中心部用粉末（Ａ）と表層部用生体材料粉末（Ｂ）との混合粉であって、内側から外側に向かって段階的に表層部用生体材料粉末（Ｂ）の配合比が多くなっている混合粉を充填した後に、複数の円筒状仕切体を引き抜き抜くことによっても、同等の複合体を製造することができる。 In the example described above, a composite was manufactured by repeating the procedure of filling the powder by standing the cylindrical partition at the center, but instead of starting from the center, filling the powder from the outer periphery, That is, even if the space formed by the inside of the die and the fourth cylindrical partition body is filled with powder first, the procedure of filling the powder is repeated sequentially toward the center portion to produce a composite. An equivalent composite can be produced.
As another example, a plurality of (four or more) cylindrical partitions having different diameters are first provided concentrically on a support base, and concentric on the outside of the largest diameter cylindrical partition. A cylindrical die is erected in the shape, and then the central cylindrical partition is filled with the central powder (A), and is formed by the outside of the cylindrical partition having the largest diameter and the inside of the cylindrical die. Are filled with the biomaterial powder (B) for the surface layer portion, and the spaces formed between the plurality of cylindrical partition bodies include the powder for the central portion (A) and the biomaterial powder for the surface layer portion (B). By filling the mixed powder in which the blending ratio of the biomaterial powder (B) for the surface layer portion is gradually increased from the inside toward the outside, and then drawing out the plurality of cylindrical partitions Also, an equivalent composite can be produced.

以下、実施例に基づいて本発明を詳細に説明する。
実施例１
各種組成の生体用同心円状傾斜機能材料の製造
粉末形成用冶具として、アルミニウム製支持台、及び４本の円筒状仕切体並びにグラファイト製ダイス、パンチを準備し、全体で５層からなる各種組成の生体用同心円状傾斜機能材料の製造を行った。 Hereinafter, the present invention will be described in detail based on examples.
Example 1
Manufacture of concentric functionally graded functional materials for living bodies of various compositions As a powder forming jig, an aluminum support base, four cylindrical partitions, a graphite die, and a punch were prepared, and various compositions consisting of five layers in total were prepared. A concentric functionally gradient material for living body was manufactured.

（１）アルミニウム製支持台は、図１に示すように中央に円柱状凸起を有し、凸起の内部に階段状凹部を備えているものを用いた。アルミニウム支持台に立設する４本の円筒状仕切体の寸法及び材質は表１に示すとおりであった。
(1) As shown in FIG. 1, an aluminum support base having a columnar protrusion at the center and a stepped recess inside the protrusion was used. The dimensions and materials of the four cylindrical partitions standing on the aluminum support were as shown in Table 1.

ダイス及びパンチは、高強度グラファイト製であって図９に示すように、ダイスの寸法は内径：２０ｍｍ、外径：５０ｍｍそして高さ：４０ｍｍであって、パンチの寸法は、外径：２０ｍｍ、高さ：２５ｍｍの円柱体である。   The die and punch are made of high-strength graphite, and as shown in FIG. 9, the die has an inner diameter of 20 mm, an outer diameter of 50 mm and a height of 40 mm, and the punch has an outer diameter of 20 mm. Height: It is a cylinder of 25 mm.

生体親和性を備えた上で、強度、骨芽細胞の足場という性質、機能を有する全５層の同心円状傾斜機能材料を得るために、図７に示すようにＴｉ粉末を芯材（第１層）に用いて、ハイドロキシアパタイト（ＨＡｐ）、または第三リン酸カルシウム（ＴＣＰ）粉末を外表面層（第５層）とし、両者の中間に両者の混合粉末の組成割合が段階的に傾斜する組成傾斜層（第２〜４層）を設けるようにした。   In order to obtain a total of five layers of concentric functionally gradient materials having biocompatibility, strength, osteoblast scaffolding properties and functions, a Ti powder is used as a core material as shown in FIG. Layer), with hydroxyapatite (HAp) or tricalcium phosphate (TCP) powder as the outer surface layer (fifth layer), the composition gradient in which the composition ratio of the mixed powder of both is stepwise in between Layers (second to fourth layers) were provided.

供試材料については、Ｔｉ粉末としては平均粒径６３〜９０μｍである純度９９．９％の純チタンを用いた。Ｔｉ粉末の粒径が大きいとハイドロキシアパタイト粉末、第三リン酸カルシウム粉末との混合が不均一となって分離するので、均一に混合させるためには、粒径６３〜９０μｍ程度が好ましい。
ハイドロキシアパタイト（ＨＡｐ）粉末としては、大平化学産業（株）製のＳＨＡｐ−１００を用いた。この粉末は、外観が白色粉末であって、粒径：３０μｍ、一次粒子の粒径：０．２〜０．３μｍ、モル比：１．６７、分子量：１００４．６４、化学式：Ｃａ10（ＰＯ4）6（ＯＨ）2の物質である。
第三リン酸カルシウム（ＴＣＰ）粉末としては、大平化学産業（株）製のβ−ＴＣＰを用いた。この粉末は、外観が白色粉末であって、粒径：１５０〜７５μｍ、モル比：１．５０、分子量：３１０．１８、化学式Ｃａ3（ＰＯ4）2の物質である。 For the test material, pure titanium having a mean particle size of 63 to 90 μm and a purity of 99.9% was used as the Ti powder. When the particle size of the Ti powder is large, mixing with the hydroxyapatite powder and the tricalcium phosphate powder becomes non-uniform and separates. Therefore, a particle size of about 63 to 90 μm is preferable for uniform mixing.
As the hydroxyapatite (HAp) powder, SHAp-100 manufactured by Ohira Chemical Industry Co., Ltd. was used. This powder is white powder in appearance, particle size: 30 μm, primary particle size: 0.2-0.3 μm, molar ratio: 1.67, molecular weight: 1004.64, chemical formula: Ca 10 (PO 4 ) 6 (OH) 2 substance.
As the tricalcium phosphate (TCP) powder, β-TCP manufactured by Ohira Chemical Industry Co., Ltd. was used. This powder is a white powder in appearance, and is a substance having a particle size: 150 to 75 μm, a molar ratio: 1.50, a molecular weight: 310.18, and a chemical formula Ca 3 (PO 4 ) 2 .

（２）生体用同心円状傾斜機能材料の製造方法は、支持台の中央に第１の円筒状仕切体を立設し、その中に第１層の粉末を充填し、次いで第２の円筒状仕切体を第１の円筒状仕切体の外側に立設し、両者で形成される空間に第２層の粉末を充填し、順次第３の円筒状仕切体、第４の円筒状仕切体、及びダイスを立設して、それぞれに第３層、第４層及び第５層の粉末を充填する工程を順次繰り返して行った。なお、高強度グラファイト製ダイス内面に剥離性を向上させるためにカーボンペーパーを装着した。 (2) A method for producing a concentric functionally gradient material for a living body is as follows: a first cylindrical partition is erected at the center of a support base, filled with a first layer of powder, and then a second cylindrical shape. The partition body is erected on the outside of the first cylindrical partition body, and the space formed by the two is filled with the second layer of powder, and sequentially the third cylindrical partition body, the fourth cylindrical partition body, Then, the process of standing up the dies and filling the powders of the third layer, the fourth layer, and the fifth layer in the respective layers was sequentially repeated. Carbon paper was attached to the inner surface of the high-strength graphite die to improve the peelability.

引き続き、円筒状仕切体を抜き取って、カーボンペーパーで蓋をし、その上から高強度グラファイト製パンチで軽く押圧して蓋をした状態にする。そして、全体を上下逆転して、支持台を取り除き、高強度グラファイト製ダイスの上部をカーボンペーパーで蓋をし、その上からもう１つの高強度グラファイト製パンチで軽く押圧して蓋をする。
このダイス及びパンチをハンドプレス機にセットして充填粉末を軽圧下した後に、放電プラズマ焼結機にセットしてパンチから通電してダイス内の粉末の焼結を行った。焼結条件は、表２に示すとおりであった。
Subsequently, the cylindrical partition is removed, covered with carbon paper, and lightly pressed from above with a high-strength graphite punch to be in a covered state. Then, the whole is turned upside down, the support is removed, the upper part of the high-strength graphite die is covered with carbon paper, and lightly pressed from there with another high-strength graphite punch, and the lid is closed.
After this die and punch were set in a hand press machine and the filled powder was lightly pressed, it was set in a discharge plasma sintering machine and energized from the punch to sinter the powder in the die. The sintering conditions were as shown in Table 2.

焼結後にダイスから焼結体を取り出し、焼結体の両端は各層が入り交わっているので、５層に組成傾斜している面が現れるまで研磨機で端面の研磨を行って、生体用同心円状傾斜機能材料を得た。   After sintering, the sintered body is taken out from the die, and the layers of the sintered body are interleaved with each other. Therefore, the end faces are polished with a polishing machine until a surface having a composition gradient appears in the five layers. A functionally gradient material was obtained.

（３）得られた生体用同心円状傾斜機能材料の各層の成分及び体積比を表３〜６に示した。なお、体積比は焼結後の体積比を示している。
表３は、中心材料（第１層）としてＴｉ粉末を用い、表層（第５層）の生体材料としてハイドロキシアパタイトを用いた例である。
(3) Tables 3 to 6 show the components and volume ratios of each layer of the obtained concentric functionally gradient material for living body. The volume ratio indicates the volume ratio after sintering.
Table 3 is an example using Ti powder as the central material (first layer) and using hydroxyapatite as the biomaterial of the surface layer (fifth layer).

表４は、中心材料（第１層）としてＴｉ粉末とハイドロキシアパタイト粉末（ＳＨＡｐ−１００）の混合粉末を使用し、表層（第５層）の生体材料粉末としてハイドロキシアパタイト粉末を用いた場合の例である。
Table 4 shows an example in which a mixed powder of Ti powder and hydroxyapatite powder (SHAp-100) is used as the central material (first layer), and hydroxyapatite powder is used as the biomaterial powder of the surface layer (fifth layer). It is.

表５は、中心材料（第１層）としてＴｉ粉末と第三リン酸カルシウム（β−ＴＣＰ）粉末の混合粉末を使用し、表層（第５層）の生体材料粉末として第三リン酸カルシウム（β−ＴＣＰ）粉末を用いた場合の例である。
Table 5 uses a mixed powder of Ti powder and tricalcium phosphate (β-TCP) powder as the central material (first layer), and tricalcium phosphate (β-TCP) as the biomaterial powder of the surface layer (fifth layer). This is an example of using powder.

表６は、中心材料（第１層）としてハイドロキシアパタイト（ＳＨＡｐ−１００）粉末を使用し、表層（第５層）の生体材料粉末として第三リン酸カルシウム（β−ＴＣＰ）粉末を用いた場合の例である。
Table 6 shows an example in which hydroxyapatite (SHAp-100) powder is used as the central material (first layer) and tricalcium phosphate (β-TCP) powder is used as the biomaterial powder for the surface layer (fifth layer). It is.

表３〜６においては、円柱の内側から順に、１層（中心）、２層、３層、４層、５層（最外層）としている。表３は中心材をＴｉとし、外層をハイドロキシアパタイト（ＳＨＡｐ−１００）とし、中間層を両者の混合層とした例であり、表５は同様にＴｉと第三リン酸カルシウム（β−ＴＣＰ）を用いた例である。表６は中心にハイドロキシアパタイト（ＳＨＡｐ−１００）を用い、外層を第三リン酸カルシウム（β−ＴＣＰ）とし、中間層を両者の混合層とした例である。
得られた生体用同心円状傾斜機能材料は、いずれも焼結時に割れが生じておらず、機械的性質の良好な材料となっていた。 In Tables 3-6, it is set as 1 layer (center), 2 layers, 3 layers, 4 layers, 5 layers (outermost layer) in order from the inner side of a cylinder. Table 3 shows an example in which the center material is Ti, the outer layer is hydroxyapatite (SHAp-100), and the intermediate layer is a mixed layer of both. Table 5 similarly uses Ti and tricalcium phosphate (β-TCP). This is an example. Table 6 shows an example in which hydroxyapatite (SHAp-100) is used at the center, the outer layer is tricalcium phosphate (β-TCP), and the intermediate layer is a mixed layer of both.
None of the obtained concentric functionally graded materials for living bodies had good mechanical properties because no cracks occurred during sintering.

実施例２
生体用同心円状傾斜機能材料の作製と生物学的特性の評価
（１）生体用同心円状傾斜機能材料の作製
実施例１と同様にして、ＨＡｐとしてＳＨＡｐ−１００（粒度：４０μｍ、太平化学工業製）を、β−ＴＣＰとして、β−ＴＣＰ（Ｌ）（粒度：５９０μｍ〜１０００μｍ、太平化学工業製）を、チタンとして水素化チタンを用い、中心部（第１層）として水素化チタンのみ、表層部（第５層）としてＳＨＡｐ−１００とβ−ＴＣＰとの体積比１：１の混合物を用いて、図１０に示す構成を有し、φ２５×２０ｍｍの円筒状の生体用同心円状傾斜機能材料を作製した。住石放電プラズマ焼結機による焼結の際の焼結温度は８００℃、焼結圧力は２２．３ＭＰa、焼結時間は８分であった。 Example 2
Preparation of biological concentric functionally gradient material and evaluation of biological characteristics (1) Preparation of biological concentric functionally gradient material As in Example 1, SHAp-100 (particle size: 40 μm, manufactured by Taihei Chemical Industries, Ltd.) ) As β-TCP, β-TCP (L) (particle size: 590 μm to 1000 μm, manufactured by Taihei Chemical Industries), titanium hydride as titanium, and only titanium hydride as the center (first layer), surface layer Using a mixture of SHAp-100 and β-TCP in a volume ratio of 1: 1 as a part (fifth layer), the cylindrical concentric functionally graded material for living body having the configuration shown in FIG. 10 and having a configuration of φ25 × 20 mm Was made. The sintering temperature at the time of sintering by the Sumiishi electric discharge plasma sintering machine was 800 ° C., the sintering pressure was 22.3 MPa, and the sintering time was 8 minutes.

（２）生物学的試験
１）傾斜材料
上記の焼結後の試験片を、図１０に示すように、中心部分から直径方向に５×５×２５ｍｍの角柱状に切り出し、家兎大腿骨埋入用に乾熱滅菌を行った。対照として、ＳＨＡｐ−１００が１００％で同様にφ２５×２０ｍｍの円筒状の放電プラズマ（ＳＰＳ）焼結体を作成後、中心部分から直径方向に５×５×２５ｍｍの角柱状に切り出し、家兎大腿骨埋入用に乾熱滅菌を行った。 (2) Biological test 1) Gradient material As shown in FIG. 10, the specimen after sintering was cut into a 5 × 5 × 25 mm prismatic shape in the diameter direction from the central portion, and the rabbit femur was buried. Dry heat sterilization was performed for use. As a control, a cylindrical discharge plasma (SPS) sintered body having a SHAp-100 of 100% and similarly φ25 × 20 mm was prepared, and then cut out into a 5 × 5 × 25 mm prismatic shape in the diameter direction from the center portion. Dry heat sterilization was performed for femoral embedding.

２）実験動物
動物実験施設にて約２週間飼育した雌性家兎（日本白色種、体重約３．０ｋｇ、三共ラボサービス）５羽を実験動物として使用した。 2) Experimental animals Five female rabbits (Japanese white species, body weight of about 3.0 kg, Sankyo lab service) kept for about 2 weeks in an animal experimental facility were used as experimental animals.

３）骨内埋入
家兎耳静脈からペントバルビタールナトリウム（ネンブタール、三共）を静脈内注射した。麻酔下にて家兎大腿骨部に塩酸リドカイン（２％キシロカインＥ、アストラゼネカ）で局所麻酔を行った。骨膜に達する切開を行い、鈍的に皮膚骨膜を剥離し大腿骨関節近傍を露出させた。５．０ｍｍ角の挿入窩を注水下で形成し、ＳＰＳ傾斜機能材料を骨髄腔内に挿入した。骨膜を吸収性縫合糸（ＶＩＣＲＩＬ ３−０、Ｅｔｈｉｃｏｎ）で埋没縫合を行い、皮弁をナイロン糸（ネスコスチャー，日本商事）にて縫合した。なお、対照群にはＨＡｐ単体を挿入し、骨膜を吸収性縫合糸で埋没縫合を行い、皮弁をナイロン糸にて縫合したものを用いた。
埋入後３ヶ月飼育したのちにそれぞれ過剰のペントバルビタールナトリウムを静脈内注射して屠殺し、填塞部周囲の骨を含めて摘出した。摘出材料は、１０％中性ホルマリン液にて２週間固定し組織切片作製に供した。試験群は，摘出した大腿骨をレジン包埋後、非脱灰切片として薄片に研磨し、ＴＲＡＰ染色を行った。これに対し、ＨＡｐのみの対照群は、摘出した大腿骨をＰｌａｎｋ Ｒｙｃｈｌｏ処方の迅速脱灰液（Ｄｅｃａｌｃｉｆｙｉｎｇ Ｓｏｌｎ． Ａ， ＷＡＫＯ）で２日脱灰後、５％硫酸ナトリウム水溶液で半日間中和して、通法に従いパラフィン包埋し薄切切片を作製して、ヘマトキシリン・エオジン重染色を行い、対照とし病理組織学的検索に供した。なお、動物実験においては本学動物実験指針に従って行った。 3) Intraosseous implantation Pentobarbital sodium (Nembutal, Sankyo) was intravenously injected from the rabbit ear vein. Under anesthesia, the rabbit femur was locally anesthetized with lidocaine hydrochloride (2% xylocaine E, AstraZeneca). An incision reaching the periosteum was made, and the skin periosteum was bluntly detached to expose the vicinity of the femoral joint. A 5.0 mm square insertion fossa was formed under water injection, and the SPS functionally gradient material was inserted into the bone marrow cavity. The periosteum was embedded and sutured with an absorbable suture (VICRIL 3-0, Ethicon), and the flap was sutured with a nylon thread (Nescostar, Nippon Shoji). In the control group, HAp alone was inserted, the periosteum was buried with an absorbable suture, and the flap was sutured with a nylon thread.
After 3 months of embedment, the animals were killed by intravenous injection of excess pentobarbital sodium, and the bones around the inoculated area were removed. The excised material was fixed in 10% neutral formalin solution for 2 weeks and used for preparation of tissue sections. In the test group, the excised femur was embedded in the resin, polished into a thin piece as a non-decalcified section, and subjected to TRAP staining. In contrast, in the HAp-only control group, the excised femur was neutralized with a 5% aqueous solution of sodium sulfate for 5 days after decalcification for 2 days with a rapid decalcification solution (Decalifying Soln. A, WAKO) formulated with Plank Rychlo. Then, paraffin-embedded and sliced sections were prepared according to a conventional method, and hematoxylin and eosin double staining was performed, and used as a control for histopathological search. Animal experiments were conducted according to the University Animal Experiment Guidelines.

４）結果
４）−１
図１１に、対照（ＨＡｐ単体）での組織反応（３ヶ月）の弱拡大図を示した。図１１においては、ＨＡｐに接している面は線維性結合組織（ａ）の層を介して線維性骨（ｂ）によって被包されている。この状態は，早期に線維性の被包が起こり、その後、化骨が起こったことを示している。層板骨（ｃ）と成熟した骨髄組織である脂肪細胞（ｄ）が認められることからも反応性の状態ではなく、安定した状態を示していると言える。
４）−２
図１２には、対照（ＨＡｐ単体）での組織反応（３ヶ月）の強拡大図を示している。強拡大では、破骨細胞（ａ）が認められ、骨の改築が行われている部位もあるが、そのようなところは少ない。骨髄細胞には、血液成分の存在が認められ、血管系の形成がある。炎症性の細胞は認められなかった。 4) Results 4) -1
FIG. 11 shows a weakly enlarged view of the tissue reaction (3 months) in the control (HAp alone). In FIG. 11, the surface in contact with HAp is encapsulated by fibrous bone (b) through a layer of fibrous connective tissue (a). This condition indicates that fibrous encapsulation occurred early, followed by ossification. From the fact that lamellar bone (c) and adipocytes (d), which are mature bone marrow tissues, are observed, it can be said that they are not in a reactive state but in a stable state.
4) -2
FIG. 12 shows a strongly enlarged view of the tissue reaction (3 months) in the control (HAp alone). In strong enlargement, osteoclasts (a) are observed, and there are some sites where bone reconstruction is performed, but there are few such places. Bone marrow cells have the presence of blood components and have vasculature formation. Inflammatory cells were not observed.

４）−３
図１３には、対照（ＨＡｐ単体）での組織反応（３ヶ月）の弱拡大図を示している。弱拡大図では、関節頭付近では、軟骨の形成（ａ）が認められた。このことからも異所性の骨化は発現して織らず、組織親和性が高いことが認められた。
４）−４
図１４に、試験群（ＳＰＳ傾斜機能材料）での組織反応（３か月）の弱拡大図を示した。図１４においては、左側水素化チタン（Ｔｉ）１００％から右側に向かってＨＡｐ１００％と徐々に変化するようにＳＰＳによって試験体に傾斜機能性を付与した。Ｔｉ１００％およびＨＡｐ１００％付近では、骨様組織が認められるが中央部では、線維性結合組織が顕著に認められた。骨様組織は，ＨＡｐ側では、試験体に接するように形成されているが、Ｔｉ側では、結合組織を介して形成されている。 4) -3
FIG. 13 shows a weakly enlarged view of the tissue reaction (3 months) in the control (HAp alone). In the weakly enlarged view, cartilage formation (a) was observed near the joint head. From this, it was confirmed that ectopic ossification occurred and did not weave, and that tissue affinity was high.
4) -4
FIG. 14 shows a weakly enlarged view of the tissue reaction (3 months) in the test group (SPS functionally gradient material). In FIG. 14, the graded functionality was imparted to the specimen by SPS so as to gradually change from 100% left-side titanium hydride (Ti) to 100% HAp toward the right side. Bone-like tissue was observed in the vicinity of 100% Ti and 100% HAp, but fibrous connective tissue was remarkably observed in the central part. The bone-like tissue is formed so as to be in contact with the test body on the HAp side, but is formed via the connective tissue on the Ti side.

４）−５
図１５に、図１４の試験群（ＳＰＳ傾斜機能材料）での組織反応（３か月）の左側の強拡大図を示した。図１５から分かるように、試験体（ａ：ＨＡｐ）と接している部分は、薄い線維性結合組織（ｂ）を介して，骨様の組織（ｃ）が線維性結合組織の走向に沿って接しているのが認められた。特に、骨様組織（ｃ）の形態が分岐の多い不規則な形状を呈していることから、骨の再構築か活発に行われていることが分かる。また、その空隙には，幼若な骨髄細胞由来と考えられる脂肪細胞（ｄ）などが認められた。 4) -5
FIG. 15 is a strong enlarged view on the left side of the tissue reaction (3 months) in the test group (SPS functionally gradient material) in FIG. As can be seen from FIG. 15, the portion in contact with the test body (a: HAp) passes through the thin fibrous connective tissue (b) and the bone-like tissue (c) follows the strike of the fibrous connective tissue. It was admitted to touch. In particular, since the shape of the bone-like tissue (c) has an irregular shape with many branches, it can be seen that bone reconstruction is actively performed. In the voids, fat cells (d) considered to be derived from young bone marrow cells were observed.

４）−６
図１６に、図１４の試験群（ＳＰＳ傾斜機能材料）での組織反応（３か月）の右側の強拡大図を示した。図１６から分かるように、Ｔｉが多く配合されてくると、材料に接している部分の組織が、線維性結合組織（ｂ）の割合がＨＡｐ ｒｉｃｈよりも多くなっている。その外側には、骨様組織（ｃ）の層があり、その間隙には脂肪細胞（ｄ）が認められる。骨様組織の形態が分岐の多い不規則な形状を呈していること、活発に骨の破壊と新生骨の再構築が行われていると考えられる。 4) -6
FIG. 16 shows a strong enlarged view on the right side of the tissue reaction (3 months) in the test group (SPS functionally gradient material) of FIG. As can be seen from FIG. 16, when a large amount of Ti is added, the ratio of the fibrous connective tissue (b) in the tissue in contact with the material is higher than that in the HAp rich. On the outside, there is a layer of bone-like tissue (c), and adipocytes (d) are observed in the gap. It is considered that the shape of the bone-like tissue has an irregular shape with many branches, and bone destruction and new bone reconstruction are being actively performed.

４）−７
以上の結果より、対照には認められない新生骨生成が傾斜材料においては認められた。すなわち、対照としたＨＡｐのみの試験体とでは、炎症性の細胞浸潤はなく、層板上骨であったにも関わらず、新生骨生成は乏しかった。これに対して傾斜材料は、配合されているＨＡｐとＴｉとの配合率の違いによって、試験体に接する組織が異なった。対照と同様にＨＡｐが接している部位は薄い線維性結合組織によって被包された外側に骨様組織の形成が認められ、Ｔｉの部位では、接している部位でＨＡＰよりも厚い線維性結合組織の被包の外側に骨様組織の形成が認められた。両者とも梁状の形態を成していることから、盛んな骨新生の反応が起こっていると考えられた。歯髄組織由来と思われる脂肪細胞は幼若であるため成熟前の反応性に富んだ状態であると考えられた。ＨＡｐとＴｉの配合の中間部分では、線維性結合組織が最も多く被包しており、その外側に骨様組織が存在した。ＨＡｐもＴｉも骨様組織の形成は認められたが、試験体との接し方には差があり、ＨＡｐは薄い結合組織を介しているのに対してＴｉは比較的厚い結合組織が介在していた。このことにより、結合組織による力学的緩衝作用の大小を材料に付与することが可能と考えられた。また、ＨＡｐは線維性結合組織の走向に沿った骨様組織の形成が認められたことから、線維性結合組織の石灰化による骨様組織の形成と考えられるが、Ｔｉは、部分的な炎症反応の後に出現する幼若な骨髄細胞由来の脂肪細胞による新生骨生成であるため走向性を示さなかったと考えられた。骨の形状による外力への抵抗力を機能的に付与することが可能であると考えられた。 4) -7
From the above results, new bone formation not observed in the control was observed in the gradient material. That is, the HAp-only test specimen used as a control had no inflammatory cell infiltration, and the formation of new bone was scarce even though it was bone on the lamina. On the other hand, in the gradient material, the structure in contact with the test specimen was different depending on the difference in the mixing ratio between HAp and Ti. Similar to the control, formation of bone-like tissue is observed on the outer side encapsulated by thin fibrous connective tissue at the site where HAp is in contact, and at the Ti site, fibrous connective tissue that is thicker than HAP at the contacted site. The formation of bone-like tissue was observed outside the capsule. Since both were in the form of a beam, it was thought that a vigorous osteogenesis reaction occurred. The adipocytes that seemed to be derived from dental pulp tissues were considered to be rich in reactivity before maturation because they were young. In the middle part of the blend of HAp and Ti, the fibrous connective tissue was most encapsulated, and the bone-like tissue was present on the outside. Bone-like tissue formation was observed in both HAp and Ti, but there was a difference in the way of contact with the specimen, HAp was through a thin connective tissue, whereas Ti was interspersed with a relatively thick connective tissue. It was. Thus, it was considered that the mechanical buffering effect by the connective tissue can be imparted to the material. HAp is considered to form bone-like tissue due to calcification of fibrous connective tissue because formation of bone-like tissue along the direction of fibrous connective tissue was observed. It was thought that it showed no chemotactic property because it was a new bone formation by adipocytes derived from young bone marrow cells that appeared after the reaction. It was thought that resistance to external force due to the shape of the bone could be functionally applied.

以上に、詳細に説明したとおり、本発明の生体用同心円状傾斜機能材料は、曲げ強度、ヤング率などの機械的強度において優れており、また、骨補填材料として使用した場合に、活発に骨の破壊と新生骨の再構築が起こり、生体反応性においても優れている。従って、本発明の生体用同心円状傾斜機能材料は、骨補填材、人工歯根、歯科用セメント等の生体材料として極めて有用である。   As described above in detail, the biomedical concentric functionally gradient material of the present invention is excellent in mechanical strength such as bending strength and Young's modulus, and when used as a bone prosthetic material, Destruction and remodeling of new bone occur, and the bioreactivity is also excellent. Therefore, the biomedical concentric functionally gradient material of the present invention is extremely useful as a biomaterial for bone filling materials, artificial tooth roots, dental cements and the like.

支持台の構成を示す図で、図１（ａ）は正面断面図で、図２（ｂ）は平面図である。It is a figure which shows the structure of a support stand, Fig.1 (a) is front sectional drawing, FIG.2 (b) is a top view. 支持台の中央凹部に第１の円筒状仕切体を立設し、第１層となるチタン粉末を充填した状態を示す図である。It is a figure which shows the state which erected the 1st cylindrical partition in the center recessed part of the support stand, and was filled with the titanium powder used as the 1st layer. 第１の円筒状仕切体の外側に第２の円筒状仕切体を仕切体上に立設し、第２層となる混合粉末を充填した状態を示す図である。It is a figure showing the state where the 2nd cylindrical partition was erected on the partition outside the 1st cylindrical partition, and the mixed powder used as the 2nd layer was filled up. 第１〜第４の円筒状仕切体及び円筒状ダイスを仕切体上に立設し、チタン粉末、混合粉末及びハイドロキシアパタイト粉末を充填した状態を示す図である。It is a figure which shows the state which set up the 1st-4th cylindrical partition body and the cylindrical die on the partition body, and was filled with titanium powder, mixed powder, and hydroxyapatite powder. ダイス、パンチ内に充填粉末を保持した状態を示す図である。It is a figure which shows the state which hold | maintained the filling powder in the dice | dies and the punch. 放電プラズマ焼結装置を用いて焼結を行なう状態を示す図である。It is a figure which shows the state which sinters using a discharge plasma sintering apparatus. 全５層からなる生体用同心円状傾斜機能材料を示す図である。It is a figure which shows the concentric-form gradient functional material for biological bodies which consists of all the five layers. 支持台の他の例の構造を示す図で、（ａ）は正面断面図で、図２（ｂ）は平面図である。It is a figure which shows the structure of the other example of a support stand, (a) is front sectional drawing, FIG.2 (b) is a top view. 実施例１で用いたダイス及びパンチの寸法を示す図である。It is a figure which shows the dimension of the die | dye and punch which were used in Example 1. FIG. 実施例２で作製した生体用同心円状傾斜機能材料の構成および実施例２の生物学的試験で用いた傾斜材料の試験片の形状を示す。The structure of the concentric functionally gradient material for living body produced in Example 2 and the shape of the test piece of the gradient material used in the biological test of Example 2 are shown. 実施例２で実施した生物学的試験において、対照として用いたＨＡｐ単体の３ヶ月後の組織反応を示す弱拡大図である。図１１において、ａは線維性結合組織、ｂは線維性骨、ｃは層板骨、ｄは脂肪細胞を示す。In the biological test conducted in Example 2, it is the weak enlarged view which shows the tissue reaction after 3 months of the HAp single-piece | unit used as a control | contrast. In FIG. 11, a is a fibrous connective tissue, b is a fibrous bone, c is a lamellar bone, and d is an adipocyte. 実施例２で実施した生物学的試験において、対照として用いたＨＡｐ単体の３ヶ月後の組織反応を示す強拡大図である。図１２において、ａは破骨細胞、ｂは骨髄細胞を示す。In the biological test implemented in Example 2, it is a strong enlarged view which shows the tissue reaction after 3 months of the HAp single-piece | unit used as a control | contrast. In FIG. 12, a indicates osteoclasts and b indicates bone marrow cells. 実施例２で実施した生物学的試験において、対照として用いたＨＡｐ単体の３ヶ月後の組織反応を示す弱拡大図である。図１３において、ａは軟骨の形成を示す。In the biological test conducted in Example 2, it is the weak enlarged view which shows the tissue reaction after 3 months of the HAp single-piece | unit used as a control | contrast. In FIG. 13, a indicates the formation of cartilage. 実施例２で実施した生物学的試験において、傾斜材料の３ヶ月後の組織反応を示す弱拡大図である。In the biological test implemented in Example 2, it is a weak enlarged view which shows the tissue reaction after 3 months of a gradient material. 図１４の弱拡大図の左側の強拡大図である。図１５において、ｂは線維性結合組織、ｃは線維性骨、ｄは脂肪細胞を示す。It is the strong enlarged view on the left side of the weak enlarged view of FIG. In FIG. 15, b represents fibrous connective tissue, c represents fibrous bone, and d represents adipocytes. 図１４の弱拡大図の右側の強拡大図である。図１６において、ｂは線維性結合組織、ｃは線維性骨、ｄは脂肪細胞を示す。It is the strong enlarged view on the right side of the weak enlarged view of FIG. In FIG. 16, b indicates fibrous connective tissue, c indicates fibrous bone, and d indicates adipocytes.

符号の説明Explanation of symbols

１ 支持台
２ 円柱状凸起
３ 階段状凹部
４ 同心円状溝
５ 中央凹部
６ 第１の円筒状仕切体
７ チタン粉末
８ 第２の円筒状仕切体
９ 混合粉末（ａ）
１０ 第３の円筒状仕切体
１１ 第４の円筒状仕切体
１２ グラファイト製ダイス
１３ ハイドロキシアパタイト粉末
１４ グラファイト製パンチ
１５ 圧粉体
１６ 真空室
１７ 電源
１８ 加圧ラム
１９ 第１層
２０ 第２層
２１ 第３層
２２ 第４層
２３ 第５層
２４ 生体用同心円状傾斜機能材料 DESCRIPTION OF SYMBOLS 1 Support stand 2 Cylindrical protrusion 3 Stair-shaped recessed part 4 Concentric groove 5 Center recessed part 6 1st cylindrical partition 7 Titanium powder 8 2nd cylindrical partition 9 Mixed powder (a)
DESCRIPTION OF SYMBOLS 10 3rd cylindrical partition 11 4th cylindrical partition 12 Graphite die 13 Hydroxyapatite powder 14 Graphite punch 15 Compact 16 Vacuum chamber 17 Power supply 18 Pressurization ram 19 1st layer 20 2nd layer 21 3rd layer 22 4th layer 23 5th layer 24 Concentric functionally gradient material for living body

Claims (4)

直径方向に中心部、中間層および表層部からなる生体用同心円状傾斜機能材料であって、中心部は機械的強度が高い材料、表層部は生体適合性が高い材料からなり、中間層は、機械的強度が高い材料と生体適合性が高い材料とを混合した層であって、機械的強度が高い材料と生体適合性が高い材料との混合割合が表層に向かって生体適合性が高い材料が多くなる組成傾斜した３層以上からなる、生体用同心円状傾斜機能材料であって、
機械的強度が高い材料として、チタンおよびハイドロキシアパタイト（ＨＡｐ）の少なくとも１種と、更に第三リン酸カルシウム（ＴＣＰ）を用いる；機械的強度が高い材料としてチタンとＨＡｐの混合物を、生体適合性が高い材料として、ＨＡｐを用いる；機械的強度が高い材料としてチタンとＴＣＰ混合物を、生体適合性が高い材料として、ＴＣＰを用いる；あるいは機械的強度が高い材料としてＨＡｐを、生体適合性が高い材料として、ＴＣＰを用いる、ことを特徴とする生体用同心円状傾斜機能材料。 Concentric functionally graded material for living body consisting of a central part, an intermediate layer and a surface layer part in the diameter direction, the central part is made of a material having high mechanical strength, the surface layer part is made of a material having high biocompatibility, and the intermediate layer is A material that has a mixture of a material with high mechanical strength and a material with high biocompatibility, and the mixing ratio of the material with high mechanical strength and the material with high biocompatibility is high in biocompatibility toward the surface layer. A bioconcentric functionally gradient material composed of three or more layers with an increased composition ,
As a material having high mechanical strength, at least one of titanium and hydroxyapatite (HAp) and further tricalcium phosphate (TCP) are used; as a material having high mechanical strength, a mixture of titanium and HAp is highly biocompatible. Use HAp as material; use titanium and TCP mixture as material with high mechanical strength, use TCP as material with high biocompatibility; or use HAp as material with high mechanical strength as material with high biocompatibility A concentric functionally gradient material for living bodies, characterized by using TCP . ＴＣＰとして、β−ＴＣＰを用いる請求項１の生体用同心円状傾斜機能材料。 As TCP, biomedical concentric FGM of claim 1 using a beta-TCP. チタンとして、水素化チタンを用いる請求項１または２の生体用同心円状傾斜機能材料。 The bioconcentric concentric functionally gradient material according to claim 1 or 2 , wherein titanium hydride is used as titanium. 機械的強度が高い材料と、生体適合性が高い材料とを円柱状に複合化させ、かつ、両者の中間層として、機械的強度が高い材料と生体適合性が高い材料との混合割合が段階的に異なる３層以上の組成傾斜層を介在させて作製した成形体を放電プラズマ焼結法により焼結して得られる請求項１から３のいずれかの生体用同心円状傾斜機能材料。 A material with high mechanical strength and a material with high biocompatibility are combined in a cylindrical shape, and the mixing ratio between the material with high mechanical strength and the material with high biocompatibility is the intermediate layer between them. The concentric gradient functional material for living body according to any one of claims 1 to 3 , which is obtained by sintering a molded body produced by interposing three or more compositionally gradient layers different from each other by a discharge plasma sintering method.
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