JP2801022B2 - Antimicrobial hydroxyapatite composition and method for producing the same - Google Patents
Antimicrobial hydroxyapatite composition and method for producing the sameInfo
- Publication number
- JP2801022B2 JP2801022B2 JP1122958A JP12295889A JP2801022B2 JP 2801022 B2 JP2801022 B2 JP 2801022B2 JP 1122958 A JP1122958 A JP 1122958A JP 12295889 A JP12295889 A JP 12295889A JP 2801022 B2 JP2801022 B2 JP 2801022B2
- Authority
- JP
- Japan
- Prior art keywords
- calcium phosphate
- antibacterial
- hydroxyapatite
- zinc
- silver
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/12—Powders or granules
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
- A01N59/26—Phosphorus; Compounds thereof
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Environmental Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- Zoology (AREA)
- Pest Control & Pesticides (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Toxicology (AREA)
- Materials For Medical Uses (AREA)
- Dental Preparations (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明は、生体親和性の良好な材料として、人工骨、
人工歯根、骨欠損部補填材、歯科用セメント、歯磨き及
び化粧品など、医科、歯科、衛生用品分野に広く使用さ
れているハイドロキシアパタイトに、銀、銅及び亜鉛か
ら選ばれた抗菌性金属イオンを担持させた抗菌性リン酸
カルシウム系化合物を添加することを特徴とする抗菌性
ハイドロキシアパタイト組成物及びその製造法に関する
ものである。DETAILED DESCRIPTION OF THE INVENTION (Industrial application field) The present invention relates to artificial bone,
Hydroxyapatite widely used in the medical, dental and hygiene fields, such as artificial roots, bone defect filling materials, dental cements, toothpastes and cosmetics, carries antibacterial metal ions selected from silver, copper and zinc. The present invention relates to an antibacterial hydroxyapatite composition characterized by adding an antibacterial calcium phosphate-based compound and a method for producing the same.
（従来の技術） 生体に使用する材料は、使用時の雑菌付着、繁殖を防
ぐよう、加熱滅菌又はエチレンオキサイド滅菌などが行
われ滅菌下に保存され、使用に際しては雑菌汚染のない
よう細心の注意が払われている。それにもかかわらずエ
チレンオキサイドによる滅菌は、エチレンオキサイドが
材料に残留している可能性があり、又使用時に汚染され
る可能性も皆無であるとは言えない。一方このような材
料は病巣部に使用されることが多いので、歯がそれらに
繁殖する可能性も高いと言える。リン酸カルシウム系化
合物であるハイドロキシアパタイトは生体骨と同一の組
成を有しているので生体親和性が良好で、生体材料とし
て最も優れているが、蛋白質、アミノ酸、その他有機物
を容易に吸着する性質を有するため、細菌の吸着も著し
く、このため細菌が繁殖し易い欠点を有している。従っ
てハイドロキシアパタイトを生体材料として使用するに
は、特に細菌汚染に対する配慮が必要である。このため
抗菌剤の使用が考えられているが、従来の抗菌剤は熱に
弱く、殆んどが水に溶解性の有機物質であるため、熱加
工がむづかしく、又生体内で長期間安全に使用できる抗
菌剤は少ない。一方銀、銅及び亜鉛などの金属及びそれ
らの塩が、強い抗菌力を有することが認められており、
繊維、合成樹脂などにそれらを分散、吸着、又はコーテ
ィングさせたりしてその抗菌作用を利用する方法が提案
されており、これら金属及びそれらの塩の抗菌力は、そ
れらの金属イオンによって生ずることが明らかとされて
いる。然しながらそれらを吸着、又はコーティングさせ
た物体は、金属イオンの溶出が多く、従って、毒性が出
やすく、加えて対応する陰イオンの影響も考慮する必要
があり、加えて合成樹脂などに分散型させて得られた物
体は、金属イオンの表面露出が少いため分散物体の抗菌
力が比較的弱いという欠点を有している。(Prior art) Materials used for living organisms are heat-sterilized or ethylene oxide-sterilized and stored under sterile conditions to prevent bacterial adhesion and propagation during use. Care must be taken to avoid contamination by bacteria during use. Have been paid. Nevertheless, sterilization with ethylene oxide does not mean that ethylene oxide may remain in the material and that there is no possibility of contamination during use. On the other hand, since such materials are often used for lesions, it can be said that teeth are more likely to propagate on them. Hydroxyapatite, a calcium phosphate compound, has the same composition as living bone, so it has good biocompatibility and is the best as a biomaterial, but has the property of easily adsorbing proteins, amino acids, and other organic substances. Therefore, the bacteria are remarkably adsorbed, which has a disadvantage that the bacteria can easily propagate. Therefore, in order to use hydroxyapatite as a biomaterial, special attention must be paid to bacterial contamination. For this reason, the use of antibacterial agents has been considered. However, conventional antibacterial agents are weak to heat, and most of them are organic substances that are soluble in water. Few antimicrobial agents can be used safely. On the other hand, metals such as silver, copper and zinc and their salts have been recognized to have strong antibacterial activity,
There has been proposed a method of dispersing, adsorbing, or coating fibers, synthetic resins, or the like to utilize their antibacterial action.The antibacterial activity of these metals and their salts may be caused by their metal ions. It is clear. However, the objects on which they have been adsorbed or coated have a large amount of metal ions eluted, and therefore are liable to be toxic. In addition, it is necessary to consider the effects of the corresponding anions. The resulting object has the disadvantage that the antimicrobial activity of the dispersed object is relatively weak due to low surface exposure of metal ions.
（発明が解決しようとする課題） 本発明は、他の物質と容易に混合可能で、安全に長時
間抗菌性を有するので、従来の生体材料のように雑菌に
よる汚染を考慮する必要がなく取扱いが容易な上、生体
親和性の良好な、粉体材料及びその製造法を提供するも
のである。(Problems to be Solved by the Invention) The present invention can be easily mixed with other substances and has a long-term antibacterial property safely, so that it is not necessary to consider contamination by various bacteria unlike conventional biomaterials, so that it can be handled. To provide a powder material and a method for producing the same, which are easy to use and have good biocompatibility.
（課題を解決するための手段及び作用） 前記したようにハイドロキシアパタイトは生体材料と
して加めて優れた特性を有する為、各種用途に使用され
ているが、雑菌の繁殖し易いという欠点を有している。
この欠点を除去する為、本発明は、ハイドロキシアパタ
イトのような生体親和性が優れているが雑菌の繁殖し易
い生体材料に化学親和性のあるリン酸カルシウム系化合
物に抗菌性金属イオンを担持させたものを混合すること
により、抗菌性を有するハイドロキシアパタイト組成物
を提供し、それを生体材料として使用することを提案し
ている。本願方法により、得られる抗菌性ハイドロキシ
アパタイト組成物は、ハイドロキシアパタイトに抗菌性
金属イオンを担持したハイドロキシアパタイト自身、又
はハイドロキシアパタイトと同様、リン酸とカルシウム
とよりなり、ハイドロキシアパタイトとの化学親和性に
優れたリン酸カルシウム系化合物、即ち第２リン酸カル
シウム、第３リン酸カルシウム、非晶質リン酸カルシウ
ムに抗菌性金属イオンを担持したものを単独で、又はそ
の混合物を添加し混合することにより得られる。(Means and Action for Solving the Problems) As described above, hydroxyapatite is used for various purposes because it has excellent properties in addition to a biomaterial, but has a drawback that various bacteria are easily propagated. ing.
In order to eliminate this drawback, the present invention is a biomaterial having excellent biocompatibility such as hydroxyapatite, but having a biocompatibility of various bacteria. It has been proposed to provide a hydroxyapatite composition having antibacterial properties by mixing the same and to use it as a biomaterial. According to the method of the present invention, the obtained antibacterial hydroxyapatite composition comprises hydroxyapatite itself carrying antibacterial metal ions on hydroxyapatite, or, like hydroxyapatite, is composed of phosphoric acid and calcium, and has a chemical affinity with hydroxyapatite. An excellent calcium phosphate-based compound, that is, a substance obtained by supporting antibacterial metal ions on dibasic calcium phosphate, tribasic calcium phosphate, or amorphous calcium phosphate alone or a mixture thereof is added and mixed.
一般に、リン酸水溶液をカルシウム塩で処理すると、
種々のリン酸カルシウム系化合物を生成することを文献
は明らかにしている。例えば、工化誌70［３］269（196
7）では、CaO/P2O5モル比２付近、温度20℃又は45℃で
処理するとき、反応液のpHを酸性（４〜５）に保持する
と第２リン酸カルシウム〔DCP CaHPO4・2H2O〕が、反応
液pHを6.5に保持するとDCPと少量のアパタイト〔HAP・n
H2O〕との混合物が得られることが報ぜられ、Gypsum ＆
Lime No.165、53（1980）には、CaO/P2O5モル比3.00及
び3.3でCa2+およびPO4 3-を含む各水溶液を反応させる
と、反応液の濃度及びpHにより生成する塩の種類を異に
し、pHを５〜６以下に保持するとCaHPO4・2H2Oが、pHを
それより上げると水酸アパタイト〔HAP・nH2O〕が主と
して生成すると報じている。又、バイオセラミックス
〔技報堂刊、山口・柳田編〕には、Ca2+を含むアルカリ
性溶液に、リン酸を含む溶液を徐々に滴下すると、Ca/P
モル比1.2〜1.7の非晶質リン酸カルシウム〔ACP Ca3（P
O4）２・nH2O〕が得られる旨記載され、無機リン化学
〔講談社サイエンティフィク、金沢孝文編〕にはACPを
そのまま母液に接触させておくか、水分と共存させてお
くと、HAPに変化する旨記載されている。Generally, when a phosphoric acid aqueous solution is treated with a calcium salt,
The literature discloses that it produces various calcium phosphate compounds. For example, the industrialization magazine 70 [3] 269 (196
In 7), when the reaction is performed at a CaO / P 2 O 5 molar ratio of about 2 and a temperature of 20 ° C. or 45 ° C., if the pH of the reaction solution is kept acidic (4 to 5), dicalcium phosphate [DCP CaHPO 4 .2H 2 O], when the reaction solution pH is maintained at 6.5, DCP and a small amount of apatite (HAP
H 2 O], and Gypsum &
Lime Nos. 165 and 53 (1980) react with each aqueous solution containing Ca 2+ and PO 4 3- at a CaO / P 2 O 5 molar ratio of 3.00 and 3.3, depending on the concentration and pH of the reaction solution. was different from the type of salt, when holding the pH 5 to 6 below CaHPO 4 · 2H 2 O is, raising than the pH hydroxyapatite [HAP · nH 2 O] is reported mainly generated. In addition, in bioceramics (published by Gihodo, edited by Yamaguchi and Yanagida), a solution containing phosphoric acid is gradually dropped into an alkaline solution containing Ca2 + , and Ca / P
Amorphous calcium phosphate [ACP Ca 3 (P
O 4) described 2 · nH 2 O] that the obtained inorganic phosphorus chemical [Kodansha Scientific, either leave it in contact with the mother liquor the ACP Takafumi Kanazawa ed], when allowed to coexist with water, It is described that it changes to HAP.
このように、リン酸水溶液をカルシウム塩で処理して
得られるリン酸カルシウム系化合物は、その処理条件に
より異なり、特にCa/Pモル比、反応液pH、反応時間の影
響が大で、得られるリン酸カルシウム系化合物は、反応
条件によりDCP、ACP、HAP・nH2O及びそれらの混合物と
変化する。即ち、反応液のpHを酸性に保持することによ
りDCPが塩基性に保持することによりACPが主として生成
され、PHの変化又は反応時間により、それらがHAP・nH2
Oに変化してゆくものと考えられる。然しながら、リン
酸水溶液をカルシウム塩で処理して得られるこれらのリ
ン酸カルシウム系化合物は、いずれもカルシウム及びリ
ン酸イオンよりなるものであるので、類似した物理、化
学的性質を有し、ハイドロキシアパタイトに強い化学親
和性を有する。As described above, the calcium phosphate-based compound obtained by treating an aqueous solution of phosphoric acid with a calcium salt varies depending on the treatment conditions, and the influence of the Ca / P molar ratio, the pH of the reaction solution, and the reaction time is particularly large. The compound changes into DCP, ACP, HAP.nH 2 O and a mixture thereof depending on the reaction conditions. That, DCP ACP is generated mainly by the holding basic by maintaining the pH of the reaction solution is acidified, by a change or reaction time of PH, they HAP · nH 2
It is thought to change to O. However, since these calcium phosphate-based compounds obtained by treating a phosphoric acid aqueous solution with a calcium salt are all composed of calcium and phosphate ions, they have similar physical and chemical properties and are resistant to hydroxyapatite. Has chemical affinity.
本発明に言うリン酸カルシウム系化合物とは、リン酸
水溶液を、Ca/ρモル比0.7〜1.7で、カルシウム塩で処
理し、必要に応じて反応液のpHを調整して得られるリン
酸カルシウム系化合物を意味し、DCP、ACP、HAP・nH2O
及びこれらの混合物を含むものである。本発明では、反
応液のPH及び反応時間を限定し、比較的純度の高いDC
P、ACP及びHAP・nH2Oを採取し、リン酸カルシウム系化
合物として使用することも可能であるが、これらの化合
物はいずれも類似した物理化学的性質を有し、ハイドロ
キシアパタイトとの化学的親和性が極めて優れているの
で、わざわざそれらの化合物を得る反応条件下で生成さ
せた純粋なリン酸カルシウム化合物を使用する必要はな
く、適切な反応条件下で得られたリン酸カルシウム系化
合物をそのまま使用し得る。即ち、後述する例１では、
CaCl2溶液にNa2HPO4溶液を添加（Ca/ρモル比5/6）し、
生じた生成物、即ちDCPを主成分とすると考えられるリ
ン酸カルシウム系化合物を、例４では、アンモニア性で
CaCl2とNa2HPO4とを反応させた（Ca/ρモル比10/6）で
生じたリン酸カルシウム系化合物を、例６では、アルカ
リ性であるCa（OH）２にリン酸を反応させて生じた生成
物、即ちACPを主成分とすると考えられるリン酸カルシ
ウム系化合物を、例８では例６で得たACPを充分熟成し
て得られたHAP・nH2Oを、リン酸カルシウム系化合物と
して、そのまま使用している。The calcium phosphate compound according to the present invention means a calcium phosphate compound obtained by treating a phosphoric acid aqueous solution with a calcium salt at a Ca / ρ molar ratio of 0.7 to 1.7 and adjusting the pH of the reaction solution as necessary. And DCP, ACP, HAP ・ nH 2 O
And mixtures thereof. In the present invention, the pH of the reaction solution and the reaction time are limited, and DC of relatively high purity is used.
P, taken ACP and HAP · nH 2 O, it is also possible to use as a calcium phosphate-based compound, any of these compounds have physicochemical properties that are similar, the chemical affinity with hydroxyapatite Is extremely excellent, so that it is not necessary to use a pure calcium phosphate compound generated under the reaction conditions for obtaining those compounds, and the calcium phosphate-based compound obtained under appropriate reaction conditions can be used as it is. That is, in Example 1 described below,
Add Na 2 HPO 4 solution to CaCl 2 solution (Ca / ρ molar ratio 5/6),
In Example 4, the resulting product, a calcium phosphate-based compound considered to be mainly composed of DCP,
A calcium phosphate compound produced by reacting CaCl 2 with Na 2 HPO 4 (Ca / ρ molar ratio 10/6) is produced in Example 6 by reacting phosphoric acid with alkaline Ca (OH) 2. In Example 8, HAP · nH 2 O obtained by sufficiently aging the ACP obtained in Example 6 was used as a calcium phosphate-based compound. ing.
本発明に使用する抗菌性金属及び金属イオンは銀、銅
及び亜鉛から選ばれた金属及び金属イオンである。The antimicrobial metals and metal ions used in the present invention are metals and metal ions selected from silver, copper and zinc.
本発明による抗菌性金属担持リン酸カルシウム系化合
物は、上記の方法により得られたリン酸カルシウム系化
合物に、上記の金属イオンを担持させることによって容
易に得られる。このようにして得られた抗菌性金属担持
リン酸カルシウム系化合物を混合して得られる抗菌性ハ
イドロキシアパタイト組成物は、いずれも安定で、耐熱
性、粉末であるため生体材料、その他と混合して用いる
ことが可能である。The antibacterial metal-carrying calcium phosphate-based compound according to the present invention can be easily obtained by allowing the calcium phosphate-based compound obtained by the above method to carry the above metal ion. The antibacterial hydroxyapatite composition obtained by mixing the antibacterial metal-supported calcium phosphate-based compound obtained in this manner is stable, heat-resistant, and is used as a mixture with biomaterials and the like because it is a powder. Is possible.
抗菌性金属担持リン酸カルシウム系化合物は、リン酸
カルシウム系化合物の合成時に、抗菌性金属塩を共存さ
せることにより、或はリン酸カルシウム系化合物に金属
塩を反応させることにより容易に製造することもでき
る。The antibacterial metal-supported calcium phosphate compound can be easily produced by coexisting an antibacterial metal salt during the synthesis of the calcium phosphate compound, or by reacting the calcium phosphate compound with a metal salt.
例えば、Na2HPO4及び抗菌性金属塩、即ち銀、銅及び
亜鉛から選ばれた金属塩を含有する水溶液に、撹拌しな
がらCa/ρモル比0.7〜1.7で、塩化カルシウム溶液を滴
下し、要すればpHを調整して常法によりリン酸カルシウ
ム系化合物を生成させ、生成物を蒸留水で洗浄、乾燥、
粉砕して抗菌性金属担持リン酸カルシウム系化合物を得
る。For example, to an aqueous solution containing Na 2 HPO 4 and an antibacterial metal salt, i.e., a metal salt selected from silver, copper and zinc, a calcium chloride solution is added dropwise with stirring at a Ca / ρ molar ratio of 0.7 to 1.7, If necessary, adjust the pH to produce a calcium phosphate compound by a conventional method, wash the product with distilled water, dry,
Pulverization gives an antibacterial metal-supported calcium phosphate compound.
これらの操作において、担持された金属イオン以外
に、酸性根や金属塩、及び金属イオンがCaイオンと置換
した際生成するカルシウム塩などが、抗菌性金属担持リ
ン酸カルシウム系化合物に残留する可能性があるため、
得られた抗菌性金属担持リン酸カルシウム系化合物は充
分水洗し、これら共維物を完全に除去する必要がある。
リン酸カルシウム系化合物に担持させる抗菌性金属イオ
ンの量は、使用する抗菌性金属塩の種類、処理溶液の濃
度、温度などにより適宜選択することができる。多量の
金属イオンを担持させることは金属イオンが水中に溶出
する可能性があって好ましくなく、又少量の担持は抗菌
力を損なうので好ましくない。一般に担持金属イオンの
量は、リン酸カルシウム系化合物に対して重量で30％以
下、好ましくは５〜0.0001％程度とする。In these operations, in addition to the supported metal ions, acidic roots, metal salts, and calcium salts generated when the metal ions are replaced with Ca ions may remain in the antibacterial metal-supported calcium phosphate-based compound. For,
It is necessary to wash the obtained antibacterial metal-supported calcium phosphate compound sufficiently with water to completely remove these components.
The amount of the antibacterial metal ion to be carried on the calcium phosphate compound can be appropriately selected depending on the kind of the antibacterial metal salt used, the concentration of the treatment solution, the temperature, and the like. Carrying a large amount of metal ions is not preferable because metal ions may elute into water, and supporting a small amount of metal ions is not preferable because the antibacterial activity is impaired. Generally, the amount of the supported metal ions is 30% or less by weight, preferably about 5 to 0.0001%, based on the calcium phosphate compound.
このようにして得られた抗菌性金属担持リン酸カルシ
ウム系化合物は、長期間抗菌性を保持し、水で処理して
も金属の溶出量は数ppb程度にすぎず、安全に使用さ
れ、線維、合成樹脂などの有機物との混合も容易であ
る。このような有機物に添加、混合使用する場合、有機
物重量に対し、10％以下、好ましくは0.5〜５％程度添
加することにより充分な抗菌力を発揮する。The antibacterial metal-supported calcium phosphate compound thus obtained retains antibacterial properties for a long period of time, and the amount of metal eluted is only a few ppb even when treated with water, and it is used safely, fiber, synthetic Mixing with an organic substance such as a resin is also easy. When added to or mixed with such an organic substance, sufficient antibacterial activity is exhibited by adding 10% or less, preferably about 0.5 to 5%, based on the weight of the organic substance.
以下に実施例を示して本発明を具体的に説明する。 Hereinafter, the present invention will be described specifically with reference to examples.
例１） 0.1Mリン酸水素２ナトリウム溶液1.2中に硫
酸銅8gを加えて溶解する。この溶液に0.1M塩化カルシウ
ム溶液１を撹拌しつつ徐々に滴下し、常法によりハイ
ドロキシアパタイトを合成した。生成物を蒸留水で良く
洗い、乾燥、粉砕を行ない銅担持ハイドロキシアパタイ
ト粉末を得た（収量約13g及び銅担持量約22％）。Example 1) 8 g of copper sulfate is added to and dissolved in a 0.1 M disodium hydrogen phosphate solution 1.2. To this solution, 0.1M calcium chloride solution 1 was gradually added dropwise with stirring, and hydroxyapatite was synthesized by a conventional method. The product was thoroughly washed with distilled water, dried and pulverized to obtain a copper-supported hydroxyapatite powder (yield: about 13 g, copper-supported amount: about 22%).
例２） 硫酸銅の代りに硝酸亜鉛約6gを用いたことを除
いて、例１と同様に処理し、亜鉛担持ハイドロキシアパ
タイト粉末を得た（収量約13g及び亜鉛担持量約15
％）。Example 2) Except that about 6 g of zinc nitrate was used instead of copper sulfate, the same treatment as in Example 1 was carried out to obtain a zinc-supported hydroxyapatite powder (a yield of about 13 g and a zinc support amount of about 15 g).
%).
例３） 硫酸銅8gの代りに硫酸銅約1g、硫酸亜鉛約2gを
用いたことを除いて例１と同様に処理し、銅亜鉛担持ハ
イドロキシアパタイト粉末を得た（収量約13g、銅担持
量約2.8％及び亜鉛担持量約5.5％）。Example 3) Except that about 1 g of copper sulfate and about 2 g of zinc sulfate were used in place of 8 g of copper sulfate, the same treatment as in Example 1 was performed to obtain a copper-zinc-supported hydroxyapatite powder (yield about 13 g, amount of copper supported). About 2.8% and zinc loading about 5.5%).
例４） 硝酸銀約2gを蒸留水１に溶解し、アンモニア
水で中性からアルカリにpHを調整し、撹拌する。この水
溶液中に0.1M塩化カルシウム1.000mlと0.1Mリン酸水素
２ナトリウム600mlをそれぞれ撹拌しつつ徐々に滴下
し、溶液のpHをアンモニア水で中性からアルカリに調整
し、白色沈澱物を得た、分析の結果、白色沈澱物は銀担
持第３リン酸カルシウムであった。白色沈澱物を蒸留水
で良く洗い、乾燥、粉砕を行ない、銀担持第３リン酸カ
ルシウム粉末約9gを得た（銀担持量約10％）。Example 4) About 2 g of silver nitrate is dissolved in distilled water 1, the pH is adjusted from neutral to alkaline with aqueous ammonia, and the mixture is stirred. To this aqueous solution, 1.000 ml of 0.1 M calcium chloride and 600 ml of 0.1 M disodium hydrogen phosphate were gradually added dropwise with stirring, and the pH of the solution was adjusted from neutral to alkaline with aqueous ammonia to obtain a white precipitate. As a result of the analysis, the white precipitate was silver-carrying tribasic calcium phosphate. The white precipitate was thoroughly washed with distilled water, dried and pulverized to obtain about 9 g of a silver-supported tricalcium phosphate powder (about 10% of the silver supported).
例５） 硝酸銀約2gの代りに硝酸銀0.1g、硫酸銅0.2g、
硝酸亜鉛0.4gを用いたことを除いて、例４と同様に処理
し、銀、銅、亜鉛担持第３リン酸カルシウム粉末約9gを
得た（担持量：銀約0.6％、銅約0.8％、亜鉛約1.7
％）。Example 5) Instead of about 2 g of silver nitrate, 0.1 g of silver nitrate, 0.2 g of copper sulfate,
Except that 0.4 g of zinc nitrate was used, the same treatment as in Example 4 was carried out to obtain about 9 g of silver, copper and zinc-supported tribasic calcium phosphate powder (load: about 0.6% of silver, about 0.8% of copper and about 0.8% of zinc) About 1.7
%).
例６） 1M水酸化カルシウム溶液100ml中に硝酸銀1g、
硫酸銅0.8gを加え、0.2Mリン酸溶液を添加して撹拌し、
白色沈澱物を得た。分析の結果、白色沈澱物は銀、銅担
持非晶質リン酸カルシウムであった。白色沈殿物を蒸留
水で良く洗い、乾燥、粉砕を行ない、銀、銅担持非晶質
リン酸カルシウム粉末を得た（収量約36g、銀担持量約
1.6％及び銅担持量約0.8％）。Example 6) 1 g of silver nitrate in 100 ml of 1 M calcium hydroxide solution,
0.8 g of copper sulfate is added, a 0.2 M phosphoric acid solution is added and stirred,
A white precipitate was obtained. As a result of the analysis, the white precipitate was silver and copper-supported amorphous calcium phosphate. The white precipitate was thoroughly washed with distilled water, dried and pulverized to obtain silver and copper-carrying amorphous calcium phosphate powder (yield about 36 g, silver carrying amount about
1.6% and copper loading about 0.8%).
例７） 硝酸銀1g、硫酸銅0.8gの代りに硝酸亜鉛2g、フ
ッ化ナトリウム0.4gを用いたことを除いて、例６と同じ
処理を行い、亜鉛、フッ素担持非晶質リン酸カルシウム
粉末を得た。（収量約34g、亜鉛担持量約2.3％及びフッ
素担持量約0.5％）。Example 7 The same treatment as in Example 6 was carried out except that zinc nitrate 2 g and sodium fluoride 0.4 g were used instead of silver nitrate 1 g and copper sulfate 0.8 g, to obtain zinc and fluorine-supported amorphous calcium phosphate powder. . (Yield about 34 g, zinc loading about 2.3% and fluorine loading about 0.5%).
例８） 100mlの蒸留水にハイドロキシアパタイト10g、
硝酸銀0.5g、硫酸亜鉛1.3gを加えて撹拌する。生成物を
蒸留水で良く洗い、乾燥、粉砕を行ない、銀、亜鉛担持
ハイドロキシアパタイト粉末を得た（銀担持量約10％及
び亜鉛担持量約５％）。Example 8) 10 g of hydroxyapatite in 100 ml of distilled water,
0.5 g of silver nitrate and 1.3 g of zinc sulfate are added and stirred. The product was washed well with distilled water, dried and pulverized to obtain a hydroxyapatite powder carrying silver and zinc (about 10% of silver and about 5% of zinc).
例９） 硝酸銀0.5gの代りに硫酸銅0.8gを用いたことを
除いて例８と同じ処理を行ない、亜鉛、銅担持ハイドロ
キシアパタイト粉末を得た（亜鉛担持量約５％及び銅担
持量約３％）。Example 9 The same treatment as in Example 8 was carried out except that 0.8 g of copper sulfate was used instead of 0.5 g of silver nitrate to obtain a hydroxyapatite powder carrying zinc and copper (about 5% of zinc carried and about 0.5% of copper carried). 3%).
例10） 金属溶出試験 上記のように作成した夫々の抗菌性金属担持リン酸カ
ルシウム系化合物1gを蒸留水100ml中に入れて撹拌し、
金属の溶出量を測定した。その結果、いずれの場合も10
0ppb以下であった。Example 10) Metal dissolution test 1 g of each antibacterial metal-supported calcium phosphate compound prepared as described above was placed in 100 ml of distilled water and stirred,
The amount of metal eluted was measured. As a result, in each case 10
It was less than 0 ppb.
例11） 抗菌力試験 例１〜９の作成物をハイドロキシアパタイトに１％添
加した組成物を用いて試験を行なった。Example 11) Antibacterial activity test A test was conducted using a composition obtained by adding the prepared products of Examples 1 to 9 to hydroxyapatite at 1%.
その組成物はいずれも以下のような抗菌性を示した。 All of the compositions exhibited the following antibacterial properties.
例12） 抗菌力試験 例８の作成物を、ハイドロキシアパタイト100gに蒸留
水200ml加えたスラリー中にそれぞれ0.001％、0.005
％、0.01％、0.1添加して試験を行った。 Example 12) Antibacterial activity test The preparation of Example 8 was added to a slurry obtained by adding 200 ml of distilled water to 100 g of hydroxyapatite, and 0.001% and 0.005% respectively.
%, 0.01%, and 0.1 were added for the test.
この結果より、0.005％以上の添加で効果のあること
がわかった。 From this result, it was found that the addition of 0.005% or more was effective.
例13） 抗菌力試験 例５の作成物にバインダーを加えて圧縮成型し、500
℃で脱脂して、抗菌性金属担持第３リン酸カルシウム系
化合物100％である直径3cmのペレットを作成した。Example 13) Antibacterial test A binder was added to the product of Example 5 and compression molded.
The mixture was degreased at ℃ to prepare pellets having a diameter of 3 cm, which was 100% of an antibacterial metal-supported tricalcium phosphate compound.
そのペレット上で抗菌力試験を行った結果、以下のよ
うな抗菌性を示した。As a result of conducting an antibacterial test on the pellets, the following antibacterial properties were exhibited.
例11〜13の結果より、抗菌性金属担持リン酸カルシウ
ム系化合物自体、高い抗菌活性を有し、それ自体で抗菌
性材料としての機能及び可能性を有するが、生体材料と
して用いる場合は、リン酸カルシウム系化合物の中でも
格別生体親和性の強いハイドロキシアパタイトに添加し
て用いるのが良く、その場合0.005％までの添加で充分
な抗菌力を発揮する。 From the results of Examples 11 to 13, the antibacterial metal-supported calcium phosphate compound itself, has a high antibacterial activity, itself has the function and potential as an antibacterial material, but when used as a biomaterial, the calcium phosphate compound Among them, it is preferable to use it by adding it to hydroxyapatite which has particularly strong biocompatibility. In this case, sufficient antibacterial activity is exhibited by adding up to 0.005%.
例14） 10の蒸留水にハイドロキシアパタイト1.0K
g、硝酸銀0.0016gを加え、100℃で１時間加熱しながら
撹拌する。生成物を蒸留水で良く洗い、乾燥、粉砕を行
ない、銀を0.0001％担持した抗菌性ハイドロキシアパタ
イト粉末を得た。Example 14) Hydroxyapatite 1.0K in 10 distilled water
g and silver nitrate (0.0016 g) are added and stirred while heating at 100 ° C. for 1 hour. The product was thoroughly washed with distilled water, dried and pulverized to obtain an antibacterial hydroxyapatite powder carrying 0.0001% of silver.
この作成物について銀の溶出試験を行ったが、溶出は
認められなかった。A silver dissolution test was performed on this product, but no dissolution was observed.
又、この作成物をハイドロキシアパタイトに１％添加
した組成物を用いて抗菌力の試験を行った。また、コン
トロールとしてハイドロキシアパタイト粉末を用いて試
験を行った。その結果、以下のような抗菌性を示した。Further, an antibacterial test was carried out using a composition obtained by adding 1% of this product to hydroxyapatite. Further, a test was performed using hydroxyapatite powder as a control. As a result, the following antibacterial properties were exhibited.
（発明の効果） 本発明による抗菌性金属担持リン酸カルシウムを含有
する抗菌性ハイドロキシアパタイト組成物は、安全で生
体親和性が高いため、生体材料などに用いることができ
るばかりでなく、熱に対しても安定であるので、合成樹
脂、繊維などに混合、分散させて加熱成型することも可
能であり、繊維、プラスチック、フィルム、紙、化粧品
など、多くの物に分散させて用いることができる。 (Effect of the Invention) The antibacterial hydroxyapatite composition containing the antibacterial metal-supported calcium phosphate according to the present invention is safe and has high biocompatibility, so that it can be used not only for biomaterials but also for heat. Since it is stable, it can be mixed and dispersed in a synthetic resin, fiber or the like and then heat-molded, and can be dispersed and used in many objects such as fiber, plastic, film, paper and cosmetics.
───────────────────────────────────────────────────── フロントページの続き (58)調査した分野(Int.Cl.6，ＤＢ名) A61L 27/00──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int.Cl. 6 , DB name) A61L 27/00
Claims (2)
とリン酸水素２ナトリウムとを含む水溶液に、塩化カル
シウム水溶液をCa/Pモル比0.7〜1.7で添加し要すればpH
を調整することにより得られた抗菌性金属イオンを重量
でリン酸カルシウム系化合物に対し５〜0.0001％担持さ
せた沈降物を採取することで得られた銀、銅及び亜鉛か
ら選ばれた抗菌性イオンを担持させたリン酸カルシウム
系化合物を含有する抗菌性ハイドロキシアパタイト組成
物であって、抗菌性金属イオン担持量が、リン酸カルシ
ウム系化合物に対し、重量で５〜0.0001％である抗菌性
ハイドロキシアパタイト組成物。An aqueous calcium chloride solution is added to an aqueous solution containing an antibacterial metal salt selected from silver, copper and zinc and disodium hydrogen phosphate at a Ca / P molar ratio of 0.7 to 1.7.
The antibacterial ions selected from silver, copper, and zinc obtained by collecting a sediment carrying 5-0.0001% of the antibacterial metal ions obtained by adjusting the amount of the antibacterial metal ions with respect to the calcium phosphate compound by weight are obtained. An antibacterial hydroxyapatite composition containing a supported calcium phosphate compound, wherein the antibacterial metal ion loading is 5 to 0.0001% by weight based on the calcium phosphate compound.
シアパタイト、第２リン酸カルシウム、第３リン酸カル
シウム、または非晶質リン酸カルシウムである請求項１
のハイドロキシアパタイト組成物。2. The calcium phosphate compound is hydroxyapatite, dibasic calcium phosphate, tertiary calcium phosphate or amorphous calcium phosphate.
A hydroxyapatite composition.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/409,076 US5009898A (en) | 1988-09-29 | 1989-09-19 | Antimicrobial hydroxyapatite powders and methods for preparing them |
| GB8921505A GB2224727B (en) | 1988-09-29 | 1989-09-22 | Antimicrobial hydroxyapatite powders |
| FR8912572A FR2636811B1 (en) | 1988-09-29 | 1989-09-26 | ANTISEPTIC HYDROXYAPATITE POWDERS AND THEIR PREPARATION METHODS |
| DE3932469A DE3932469A1 (en) | 1988-09-29 | 1989-09-28 | ANTIMICROBIAL HYDROXYAPATITE POWDER AND METHOD FOR THE PRODUCTION THEREOF |
| IT2187689A IT1232344B (en) | 1988-09-29 | 1989-09-29 | HYDROXYAPATITE ANTIMICROBIAL POWDERS AND METHODS FOR THEIR PREPARATION. |
| GB9026000A GB2236676B (en) | 1988-09-29 | 1990-11-29 | Antimicrobial hydroxyapatite powders |
| US07/857,725 US5268174A (en) | 1988-09-29 | 1992-03-26 | Antimicrobial hydroxyapatite powders containing hinokitiol, protamine or sorbic acid |
| HK70292A HK70292A (en) | 1988-09-29 | 1992-09-17 | Antimicrobial hydroxyapatite powders |
| HK70192A HK70192A (en) | 1988-09-29 | 1992-09-17 | Antimicrobial hydroxyapatite powders |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24238988 | 1988-09-29 | ||
| JP63-242389 | 1988-09-29 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7268007A Division JP2859181B2 (en) | 1995-09-22 | 1995-09-22 | Antibacterial tribasic calcium phosphate and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02180270A JPH02180270A (en) | 1990-07-13 |
| JP2801022B2 true JP2801022B2 (en) | 1998-09-21 |
Family
ID=17088428
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1122958A Expired - Lifetime JP2801022B2 (en) | 1988-09-29 | 1989-05-18 | Antimicrobial hydroxyapatite composition and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2801022B2 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3051228B2 (en) * | 1991-10-31 | 2000-06-12 | 株式会社サンギ | Antibacterial tricalcium phosphate |
| JPH09303576A (en) * | 1996-05-14 | 1997-11-25 | Ngk Spark Plug Co Ltd | Ceramic valve |
| EP1329211A4 (en) * | 2000-10-06 | 2005-01-05 | Sangi Kk | Antibacterial resin |
| KR100636403B1 (en) | 2001-10-17 | 2006-10-19 | 가부시키가이샤 상기 | Anti-bacterial composite particles and anti-bacterial resin composition |
| JP6312128B2 (en) * | 2014-01-22 | 2018-04-18 | 国立大学法人茨城大学 | Method for producing phosphate-type ceramic thin film containing osteogenesis promoting substance and method for producing bone tissue implant having the thin film as a surface layer |
| CN112618802B (en) * | 2020-12-08 | 2021-12-24 | 南方医科大学口腔医院 | Fluorine-containing antibacterial invisible appliance for improving enamel demineralization and preparation method thereof |
| JPWO2023209788A1 (en) * | 2022-04-26 | 2023-11-02 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55130854A (en) * | 1979-03-31 | 1980-10-11 | Mitsubishi Mining & Cement Co | Method of burning hydroxyyapatite sintered body |
| EP0048246B1 (en) * | 1980-03-27 | 1986-05-28 | National Research Development Corporation | Antimicrobial surgical implants |
| GB8616294D0 (en) * | 1986-07-03 | 1986-08-13 | Johnson Matthey Plc | Antimicrobial compositions |
-
1989
- 1989-05-18 JP JP1122958A patent/JP2801022B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02180270A (en) | 1990-07-13 |
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