JPH0526502B2

JPH0526502B2 -

Info

Publication number: JPH0526502B2
Application number: JP59192364A
Authority: JP
Inventors: Toshio Adachi
Original assignee: Meishin KK
Current assignee: Meishin KK
Priority date: 1984-09-13
Filing date: 1984-09-13
Publication date: 1993-04-16
Also published as: JPS6171059A

Description

[Detailed description of the invention]

産業上の利用分野本発明は新規な骨、歯牙充填用組成物とその製
造方法に関する。より詳細には、医科用、歯科用
材料、特に病的・外的理由により生じた骨や歯牙
の欠損部や空隙部に充填し、当該個所に新生骨や
歯牙を発生させやすくし、後には生体の骨組織、
歯牙組織と一体化する、無機質材料或は無機質材
料と有機質材料との複合体である骨、歯牙充填用
組成物とその製造方法関する。従来技術従来、複雑骨折や骨腫瘍の切除などの場合に行
なわれる骨欠損部及び空隙部の充填方法として
は、自家骨移植、同種骨移植、異種骨移植等が知
られ利用されているが、いづれの方法も生体拒絶
反応等を生じやすく、改善さるべき多くの問題点
を含んでいる。従つて、生体適合性に優れ、使用個所並びにそ
の周辺部における造骨作用を促進し、損傷及び空
隙個所の構造や機能を修復回復せしめる人工材料
の開発が待たれている。生体の硬組織代替材料として、従来、Ni−Cr
系、Co−Cr系、Ti系等の合金材料やプラスチツ
クス材料などが用いられているが、これらの材料
は、生体内のきびしい環境下で溶解や劣化などの
変化を生じやすく、また毒素や異物形成反応など
を伴う恐れがあることから、最近では、生体との
親和性の良好なセラミツクス系の材料が注目され
るようになつてきている。例えば、Al₂O₃の単結晶もしくは多結晶体から
なる人工骨、人工関節や人工歯根、あるいは、リ
ン酸カルシウムやハイドロキシアパタイトの焼結
体からなる人工骨、人工歯根等が提案されてい
る。しかしながら、これらのインプラント材は、セ
ラミツクスに共通の硬くてもろいという欠点があ
り、これらを人工骨や人工歯根として採用するた
めには、靱性や耐衝撃性の改善など多くの問題が
残されている。また、ハイドロキシアパタイト型リン酸カルシ
ウムの粉末を生理食塩水で混和して生体の骨の欠
損部や空隙部に充填する方法も提案されている
が、填入直後は全く強度がないので使用上制約が
多い。発明が解決しようとする問題点以上詳しく述べたように、骨欠損部、突隙部の
充填材料として従来から合金、プラスチツク、セ
ラミツクス等各種のものが提案され、その使用が
試みられてきたが、生体適合性に優れ、使用個所
並びにその周辺部における造骨作用を促進し、損
傷および空隙個所の構造、機能を修復、回復させ
得る材料は今までのところ開発されていない。そこで、本発明の目的は、異物形成反応を起さ
ず生体適合性に優れ、充入直後の高い強度が必要
とされる場合にも使用出来る、圧縮耐圧強度の高
い理想的な骨及び歯牙の欠損部及び空隙部の充填
材として使用し得る組成物およびその製法を提供
することである。問題点を解決するための手段本発明者は生体適合性に優れ、填入直後の強度
にも優れた骨、歯牙等の充填材の上記の如き現状
に鑑みて、新たな充填材を開発すべく種々検討、
研究した結果、α−リン酸三カルシウムまたはそ
の原料とリン酸アルミニウムとの焼成物を主成分
とする組成物が上記条件を満足する充填材を与え
ることを見出し、本発明を完成した。即ち、本発明の組織物は、比Ca／Alが２〜
1200の範囲内にあるα−リン酸三カルシウムまた
はその原料とリン酸アルミニウムとその焼成物
と、練和液とを含むことを特徴とする流動性また
は可塑性の骨、歯牙充填用組成物である。本発明の充填材組成物は、以下に述べる特定の
方法で製造されるα−リン酸三カルシウムの微粉
末を食塩水もくしは有機酸の水溶液等と混和し
て、流動状態又は可塑状態とすることにより調製
される。本発明の組成物において使用するα−リン酸三
カルシウムまたはその原料とリン酸アルミニウム
との焼成物の製造方法は次の通りである。即ち、γ−ピロリン酸カルシウムと炭酸カルシ
ウムとを等モル量で均一に混合し、外混合物に
0.1〜30重量％のリン酸アルミニウムを添加し、
十分に乾燥させた後1000〜1300℃、好ましくは
1200℃前後で約１時間焼成し、得られる生成物を
微粉砕して粒径100μｍ以下の微粉末とすること
によつて得ることができる。また、上記の如くして得た焼成物はラバープレ
ス法等により加圧圧縮した後、再度1200〜1500
℃、好ましくは1250〜1350℃の温度下で２時間以
上焼成し、同様に微粉化処理して粒径0.5〜20μｍ
程度の微粉末とすることもできる。リン酸アルミ
ニウムの添加をこの第２の焼成工程を行う前に行
うことも可能である。上記加圧圧縮処理におい
て、圧力は高い程よく、500Kg／cm²以上であるこ
とが好ましい。このように２度に亘り焼成、微粉化処理を施す
ことは、まず第１回目の操作で焼成物またはα−
リン酸三カルシウムを形成し、次の第２の操作に
より密度の向上を図ると共に、場合によりα−リ
ン酸三カルシウムとリン酸アルミニウムとの焼成
物を形成し、それによつて耐圧強度を高めること
を意図するものである。ただし、第１回目の焼
成・微粉化により得られる生成物でも充填材組成
物の成分として十分に機能することはいうまでも
ない。リン酸アルミニウム成分は0.1〜30重量％の量
で添加することにより、組成物の強度の向上を図
ることができる。このリン酸アルミニウムは第１
回目または第２回目の焼成・微粉化操作に添加さ
れ、焼成によりAl₂O₃を形成するので、生成物中
にAl₂O₃粒子が分散されたものとなる。前記添加
量の範囲外では、生成物を生体材料として不適当
なものとしてしまうことから臨界的なものであ
り、また、生成物を硬くて脆いものとしてしま
う。このAl₂O₃は生体に対して不活性なセラミツ
ク材料であり、これを含めたことによる生体にた
いする悪影響はない。かくして得られる焼成物にに流動性、可塑性を
与えるために、またこれを硬化するために添加さ
れる練和液としては、生理食塩水、硫酸ナトリウ
ム水溶液、グリコール酸、リンゴ酸、乳酸、パン
トテン酸、グルタミン酸等の有機酸の水溶液、ア
クリル酸、マレイン酸、フマル酸、イタコン酸等
の有機酸の水溶液またはアクリル酸、マレイン
酸、フマル酸、イタコン酸等の不飽和有機酸の重
合体（共重合体を含む）の水溶液等の、従来から
歯科用セメントの分野で使用されているものでい
よい。これらは単独でもしくは２種以上の混合物
として使用できる。前記重合体以外の練和液（硬化剤）は一般に０
〜30重量％の溶液として使用され、組成物全重量
基準で０〜10重量％（溶質換算）添加される。こ
の範囲は組成物の所定硬化速度、耐圧強度を達成
するために必要な条件である。また、不飽和カルボン酸の重合体は公知の任意
の方法で製造でき、これは10〜60重量％濃度の水
溶液等として使用され、その使用量は組成物の全
重量基準で15〜60重量％（固形物換算）の範囲内
であり、前記と同様な理由から好ましい条件であ
る。練和操作法は特に限定する必要はなく、従来か
ら歯科用セメントの分野で使用されている方法の
いずれでも良く、例えばJIS−Ｔ−6602に規定さ
れるものを使用できる。作用本発明の骨、歯牙の欠損部並びに空隙部充填用
の組成物は、比Ca／Alが２〜1200の範囲内にあ
るα−リン酸三カルシウムまたはその原料、即ち
γ−ピロリン酸カルシウムと炭酸カルシウムとリ
ン酸アルミニウムとの焼成物を使用したことを特
徴とするものであり、これを既に述べたような練
和液と混合して使用することにより以下に述べる
ような各種の利点をもたらす。骨あるいは歯牙の代替材料として具備すべき重
要な物性の一つは圧縮耐圧強度である。この耐圧
強度はとりあえず、1000Kg／cm²以上であることが
好ましいとされているが、従来技術により製造さ
れるα−リン酸三カルシウムを生理食塩水、アク
リル酸重合体の水溶液等で練和して用いる場合に
達成される圧縮耐圧強度はよくてもせいぜい300
Kg／cm²程度である。驚くべきことには、本発明に
より、耐圧強度をほぼ1500〜1800Kg／cm²程度まで
高めることが可能になつた。一般に、液体と練和して流動性もしくは可塑性
とし、短時間内に硬化させた粉末材料の圧縮耐圧
強度は、粉液比（粉末と液体との重量比）との相
関性が強く、使用勝手の許容する範囲内の粘稠度
では、粉液比が大きい程、圧縮耐圧強度は大とな
る。従つて、本発明の組成物においてもその粉末
の密度が高い程良好である。本発明の第２の方法では、２度の焼成・微粉砕
処理が行われ、第２の焼成・微粉砕処理によつて
粉密度を改善することができ、これによつて組成
物の耐圧強度を1800〜2200Kg／cm²程度まで高める
ことが可能となつた。実施例以下、実施例、製造例によつて本発明を更に具
体的に説明する。製造例１リン酸水素カルシウム・二水和物、CaHPO₄・
2H₂Ｏ（２モル）を磁性るつぼに入れ、500℃で２
時間焼成し、得られる生成物をＸ−線回折にか
け、γ−ピロリン酸カルシウム（γ−Ca₂P₂O₇）
に転化したことを確認した。次にこうして得たγ
−ピロリン酸カルシウムと乾燥炭酸カルシウムと
の１：１混合物を均質になるよう十分に攪拌した
後、圧縮耐圧強度を上げるために、第１表に示す
ような配合割合でリン酸アルミニウム（AlPO₄）
を添加し、各々の温度条件で焼成し、空中放冷後
50Å〜50μｍの粉粒体とした。 INDUSTRIAL APPLICATION FIELD The present invention relates to a novel bone and tooth filling composition and a method for producing the same. More specifically, medical and dental materials are used to fill defects and voids in bones and teeth caused by pathological and external reasons, to facilitate the generation of new bone and teeth in those areas, and to later living bone tissue,
The present invention relates to a bone and tooth filling composition that is an inorganic material or a composite of an inorganic material and an organic material that is integrated with tooth tissue, and a method for producing the same. Prior Art Conventionally, autologous bone grafting, allogeneic bone grafting, xenogeneic bone grafting, etc. have been known and used as methods for filling bone defects and voids in cases such as compound fractures and bone tumor resection. Both methods are susceptible to biological rejection and have many problems that need to be improved. Therefore, there is a need for the development of an artificial material that has excellent biocompatibility, promotes bone formation in the area where it is used and its surrounding areas, and restores the structure and function of damaged and void areas. Conventionally, Ni-Cr has been used as a substitute material for biological hard tissues.
Alloy materials such as Co-Cr-based, Co-Cr-based, Ti-based, and plastic materials are used, but these materials tend to undergo changes such as dissolution and deterioration in the harsh environment of living organisms, and are also susceptible to toxins and Due to the risk of foreign body formation reactions, ceramic materials, which have good affinity with living organisms, have recently been attracting attention. For example, artificial bones, artificial joints, and artificial tooth roots made of single crystal or polycrystalline Al ₂ O ₃ , and artificial bones and artificial tooth roots made of sintered bodies of calcium phosphate and hydroxyapatite have been proposed. However, these implant materials have the same drawbacks as ceramics, such as being hard and brittle, and many issues remain before they can be used as artificial bones and artificial tooth roots, such as improving toughness and impact resistance. . In addition, a method has been proposed in which hydroxyapatite-type calcium phosphate powder is mixed with physiological saline and filled into bone defects and voids in a living body, but there are many limitations in its use as it has no strength immediately after insertion. . Problems to be Solved by the Invention As detailed above, various materials such as alloys, plastics, and ceramics have been proposed and attempted to be used as filling materials for bone defects and protrusions. Up to now, no material has been developed that has excellent biocompatibility, promotes bone formation at the site of use and its surroundings, and can repair and restore the structure and function of damaged and void areas. Therefore, the purpose of the present invention is to create ideal bones and teeth with high compressive pressure resistance that do not cause foreign body formation reactions, are excellent in biocompatibility, and can be used even when high strength is required immediately after filling. An object of the present invention is to provide a composition that can be used as a filling material for defects and voids, and a method for producing the composition. Means for Solving the Problems In view of the above-mentioned current state of filling materials for bones, teeth, etc., which have excellent biocompatibility and excellent strength immediately after filling, the present inventor has developed a new filling material. As much as possible, consider various things,
As a result of research, it was discovered that a composition whose main component is α-tricalcium phosphate or a fired product of its raw material and aluminum phosphate provides a filler that satisfies the above conditions, and the present invention was completed. That is, the tissue of the present invention has a Ca/Al ratio of 2 to 2.
A fluid or plastic bone or tooth filling composition characterized by containing α-tricalcium phosphate or its raw material within the range of 1200, aluminum phosphate, a fired product thereof, and a kneading liquid. . The filler composition of the present invention is prepared by mixing fine powder of α-tricalcium phosphate produced by the specific method described below with a saline solution, an aqueous solution of an organic acid, etc., and bringing it into a fluid or plastic state. It is prepared by The method for producing a baked product of α-tricalcium phosphate or its raw material and aluminum phosphate used in the composition of the present invention is as follows. That is, γ-calcium pyrophosphate and calcium carbonate are uniformly mixed in equimolar amounts and added to the outer mixture.
Adding 0.1-30% by weight aluminum phosphate,
1000~1300℃ after sufficient drying, preferably
It can be obtained by calcining at around 1200° C. for about 1 hour and pulverizing the resulting product into a fine powder with a particle size of 100 μm or less. In addition, the fired product obtained as described above is compressed under pressure using a rubber press method, etc., and then heated again to 1200 to 1500
℃, preferably at a temperature of 1250 to 1350℃ for 2 hours or more, and similarly pulverized to a particle size of 0.5 to 20 μm.
It can also be made into a fine powder. It is also possible to add aluminum phosphate before carrying out this second firing step. In the above pressure compression treatment, the higher the pressure, the better, and preferably 500 Kg/cm ² or more. Performing the firing and pulverization treatment twice in this way means that the fired product or α-
Forming tricalcium phosphate and improving the density through the following second operation, and optionally forming a fired product of α-tricalcium phosphate and aluminum phosphate, thereby increasing compressive strength. It is intended that However, it goes without saying that the product obtained by the first firing and pulverization can also function satisfactorily as a component of the filler composition. By adding the aluminum phosphate component in an amount of 0.1 to 30% by weight, the strength of the composition can be improved. This aluminum phosphate is the first
It is added to the second or second firing/pulverization operation and forms Al ₂ O ₃ by firing, so that Al ₂ O ₃ particles are dispersed in the product. If the amount added is outside the above range, it is critical because the product becomes unsuitable as a biological material, and it also becomes hard and brittle. This Al ₂ O ₃ is a ceramic material that is inert to living organisms, and its inclusion has no adverse effects on living organisms. The kneading liquid added to impart fluidity and plasticity to the baked product thus obtained and to harden it includes physiological saline, aqueous sodium sulfate solution, glycolic acid, malic acid, lactic acid, and pantothenic acid. , aqueous solutions of organic acids such as glutamic acid, aqueous solutions of organic acids such as acrylic acid, maleic acid, fumaric acid, itaconic acid, etc., or polymers (copolymers) of unsaturated organic acids such as acrylic acid, maleic acid, fumaric acid, itaconic acid, etc. Any one conventionally used in the field of dental cement, such as an aqueous solution of (including coalescence), may be used. These can be used alone or in a mixture of two or more. The kneading liquid (curing agent) other than the above polymer is generally 0.
It is used as a ~30% by weight solution, and is added at 0 to 10% by weight (in terms of solute) based on the total weight of the composition. This range is a necessary condition for achieving a predetermined curing speed and compressive strength of the composition. Further, the unsaturated carboxylic acid polymer can be produced by any known method, and is used as an aqueous solution with a concentration of 10 to 60% by weight, and the amount used is 15 to 60% by weight based on the total weight of the composition. (in terms of solid matter), which is a preferable condition for the same reason as above. The kneading operation method is not particularly limited, and any method conventionally used in the field of dental cement may be used, for example, those specified in JIS-T-6602 can be used. Effect The composition for filling defects and voids in bones and teeth of the present invention is composed of α-tricalcium phosphate or its raw material, that is, γ-calcium pyrophosphate, having a ratio Ca/Al in the range of 2 to 1200. It is characterized by the use of a calcined product of calcium carbonate and aluminum phosphate, and when used in combination with the kneading liquid mentioned above, it brings about various advantages as described below. . One of the important physical properties that a bone or tooth substitute material should have is compressive pressure strength. It is said that this pressure resistance strength is preferably 1000 kg/cm ² or more, but α-tricalcium phosphate produced by conventional technology is kneaded with physiological saline, an aqueous solution of acrylic acid polymer, etc. The compressive strength achieved when used in
It is about Kg/ ^cm2 . Surprisingly, the present invention has made it possible to increase the compressive strength to about 1500 to 1800 Kg/cm ² . Generally, the compressive pressure strength of a powder material that has been kneaded with a liquid to make it fluid or plastic and hardened within a short period of time has a strong correlation with the powder-liquid ratio (weight ratio of powder to liquid), making it easier to use. When the consistency is within the allowable range, the higher the powder-liquid ratio, the higher the compressive pressure strength. Therefore, also in the composition of the present invention, the higher the density of the powder, the better. In the second method of the present invention, the firing and pulverizing treatment is performed twice, and the powder density can be improved by the second firing and pulverizing treatment, thereby improving the compressive strength of the composition. It has become possible to increase the weight to about 1800-2200Kg/ ^cm2 . Examples Hereinafter, the present invention will be explained in more detail with reference to Examples and Production Examples. Production example 1 Calcium hydrogen phosphate dihydrate, CaHPO ₄ .
2H ₂ O (2 mol) was placed in a magnetic crucible and heated to 2 H 2 O at 500°C.
The resulting product was subjected to X-ray diffraction and was found to be γ-calcium pyrophosphate (γ-Ca ₂ P ₂ O ₇ ).
It was confirmed that it had changed to Next, γ obtained in this way
- After thoroughly stirring a 1:1 mixture of calcium pyrophosphate and dry calcium carbonate to make it homogeneous, aluminum phosphate (AlPO ₄ ) was added in the proportions shown in Table 1 to increase compressive pressure strength.
is added, baked under each temperature condition, and left to cool in the air.
It was made into powder and granules with a size of 50 Å to 50 μm.

【表】製造例２第１表に示した焼成物のうち、資料番号−５
の生成物を次の第２表に示す条件でラバープレス
法により圧縮加圧し、２時間焼結させ、ついで50
Å〜50μｍの粉粒体とした。[Table] Production example 2 Among the fired products shown in Table 1, document number-5
The product was compressed and pressurized using the rubber press method under the conditions shown in Table 2 below, sintered for 2 hours, and then
It was made into powder and granules with a size of Å to 50 μm.

【表】実施例１製造例１および２で得た焼成物の粉粒体を次の
練和液のいづれかで練和した。１グリコール酸20重量％水溶液２トラヒドロフランテトラカルボン酸 50重量％水溶液３ポリアクリル酸水溶液（濃度＝45％）（商品名G.C.カーボリツト液）かくして調製した本発明の組成物の圧縮耐圧強
度を測定した。結果は第３表の通りである。なお、練和操作
法、試験法は歯科用セメントJIS−Ｔ−6602に記
載の方法に準拠した。[Table] Example 1 The powders of the fired products obtained in Production Examples 1 and 2 were kneaded with any of the following kneading liquids. 1. 20% by weight aqueous solution of glycolic acid 2. 50% by weight aqueous solution of trihydrofurantetracarboxylic acid 3. Aqueous polyacrylic acid solution (concentration = 45%) (trade name: GC Carbolyte Solution) Measurement of compressive pressure strength of the composition of the present invention thus prepared did. The results are shown in Table 3. The kneading operation method and testing method were based on the method described in dental cement JIS-T-6602.

【表】発明の効果本発明の新規組成物は、従来のハイドロキシア
パタイト型リン酸カルシウム組成物とは異なり、
填入直後の初期強度に優れ、圧縮耐圧強度が高
く、生体に対する組織適合性が極めて良好であ
り、容易に多量に供給可能で、しかも使用法が簡
便である上、自家骨の不足を補い、しかも骨組織
の修復治癒を著しく促進できるという相乗効果を
発揮する等、理想的な骨及び歯牙の欠損部及び空
隙部の充填材として大いに期待できるものであ
る。[Table] Effects of the Invention The novel composition of the present invention differs from conventional hydroxyapatite-type calcium phosphate compositions in that
It has excellent initial strength immediately after insertion, high compressive pressure strength, extremely good tissue compatibility with living organisms, can be easily supplied in large quantities, is simple to use, and can compensate for the lack of autologous bone. In addition, it exhibits a synergistic effect that can significantly promote the repair and healing of bone tissue, making it highly promising as an ideal filling material for defects and voids in bones and teeth.

Claims

[Claims] 1. It is characterized by comprising a calcined product of α-tricalcium phosphate or its raw material and aluminum phosphate having a ratio Ca/A1 in the range of 2 to 1200, and a kneading liquid. Fluid or plastic bone and tooth filling compositions. 2. Claim 1, wherein the kneading liquid is selected from the group consisting of physiological saline, sodium sulfate aqueous solution, organic acid aqueous solution, unsaturated carboxylic acid polymer aqueous solution, or a mixture thereof. The composition described in Section. 3 The organic acid is glycolic acid, malic acid, lactic acid, pantothenic acid, glutamic acid, acrylic acid,
Claim 2 is selected from the group consisting of maleic acid, fumaric acid, and itaconic acid.
Compositions as described in Section. 4 The concentration of the aqueous solution of the organic acid is 0 to 30% by weight, and the amount of the organic acid used is 0 to 30% by weight based on the total weight of the composition.
4. A composition according to any one of claims 1 to 3, characterized in that the amount is 10% by weight. 5. A claim characterized in that the unsaturated carboxylic acid polymer is a polymer or copolymer having a repeating unit of at least one member selected from the group consisting of acrylic acid, maleic acid, fumaric acid, and itaconic acid. The composition according to item 4. 6 The concentration of the unsaturated carboxylic acid polymer aqueous solution is
6. The composition according to claim 5, wherein the content is 10 to 60% by weight, and the amount used is 15 to 60% by weight of the total weight of the composition in terms of solids. 7 Mix γ-calcium prophosphate and calcium carbonate in equimolar amounts, add 0.1 to 30% by weight of aluminum phosphate to the mixture, and after drying,
The powder obtained by pulverizing the product by baking at 1300℃ is mixed with physiological saline, sodium sulfate aqueous solution,
α-phosphorus having a Ca/A1 ratio within the range of 2 to 1200, which is kneaded with at least one kneading liquid selected from the group consisting of an organic acid aqueous solution or an unsaturated carboxylic acid polymer aqueous solution. A method for producing a fluid or plastic bone or tooth filling composition containing a calcined product of tricalcium acid or its raw material and aluminum phosphate, and a kneading solution. 8 The fired and pulverized powder is pressurized and compressed again.
The second step is baking at a temperature of 1200 to 1500℃ for more than 2 hours.
8. The method according to claim 7, comprising the step of firing. 9. Claim 7, characterized in that the aluminum phosphate is added before the second firing step.
The method described in section.