JP4945743B2 - Antibacterial medical prosthetic member and antibacterial treatment method for medical prosthetic member - Google Patents

Antibacterial medical prosthetic member and antibacterial treatment method for medical prosthetic member Download PDF

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JP4945743B2
JP4945743B2 JP2005233130A JP2005233130A JP4945743B2 JP 4945743 B2 JP4945743 B2 JP 4945743B2 JP 2005233130 A JP2005233130 A JP 2005233130A JP 2005233130 A JP2005233130 A JP 2005233130A JP 4945743 B2 JP4945743 B2 JP 4945743B2
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浩樹 二川
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Hiroshima University NUC
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Description

本発明は、抗菌性医療用補綴部材及び医療用補綴部材の抗菌処理方法に係り、特にチタン又はチタン合金製の入れ歯、インプラント,クラウンやブリッジ,インレー,前装冠などに好適な抗菌性医療用補綴部材及び医療用補綴部材の抗菌処理方法に関する。   The present invention relates to an antibacterial medical prosthetic member and an antibacterial treatment method for a medical prosthetic member, and particularly suitable for antibacterial medical use for dentures, implants, crowns, bridges, inlays, anterior crowns, etc. made of titanium or titanium alloy. The present invention relates to an antibacterial treatment method for a prosthetic member and a medical prosthetic member.

チタン又はチタン合金は耐食性に優れ強度が高いばかりでなく軽く、人体に対し害がなく金属アレルギーを引き起こすこともないので、人工骨やインプラント等医療用補綴部材として利用されている。   Titanium or titanium alloys are not only excellent in corrosion resistance but high in strength, are light, do not harm the human body and do not cause metal allergy, and are used as medical prosthetic members such as artificial bones and implants.

このようなチタン又はチタン合金をインプラント等の歯科医療用の補綴部材として利用する場合は、人目にさらされる部位に使用されることが多いため審美性を高めることが求められている。例えば特許文献1に、イオンプレーティングにより純チタンを基材としてなる人工歯根であって、該人工歯根の義歯装着部に当たるポスト部分にのみ、黄金色の窒化チタン層を形成せしめた人工歯根が提案されている。そして、窒化チタン皮膜の厚さを0.5〜1.0μmとすることによって患部の状況に合わせた微妙な色調を人工歯根に与えることができることが開示されている。   When such titanium or titanium alloy is used as a prosthetic member for dentistry such as an implant, it is often used for a part exposed to the human eye, so that it is required to improve aesthetics. For example, Patent Document 1 proposes an artificial tooth root made of pure titanium by ion plating, in which a golden titanium nitride layer is formed only on the post portion corresponding to the artificial tooth mounting portion of the artificial tooth root. Has been. And it is disclosed that a delicate color tone adapted to the condition of the affected part can be given to the artificial tooth root by setting the thickness of the titanium nitride film to 0.5 to 1.0 μm.

また、そのような歯科医療用の補綴部材として用いる場合は、口腔内の雑菌と接触する機会が多いため抗菌性に優れたものが求められている。とくに口腔内には400〜500種類の微生物が生息しており、装着される補綴物にバイオフィルムを形成し、さまざまな病原性を示すことが報告されている。病原性を示す菌には、入れ歯を支える歯のう蝕・歯周病を引き起こす菌が有名であるが、この他にインプラント周囲炎や口腔内の微生物の誤嚥による誤嚥性肺炎などを引き起こす多くの多様な菌があり、歯科医療用の補綴物自身に抗菌性を与えることは非常に有意義なことである。   Moreover, when using as such a prosthetic member for dentistry, since there are many opportunities to come into contact with germs in the oral cavity, those having excellent antibacterial properties are required. In particular, 400 to 500 kinds of microorganisms inhabit the oral cavity, and it has been reported that biofilms are formed on the prosthesis to be attached and show various pathogenicity. Among the bacteria that show pathogenicity, bacteria that cause dental caries and periodontal disease that support dentures are well known, but in addition to this, they cause peri-implantitis and aspiration pneumonia caused by aspiration of microorganisms in the oral cavity. There are many different bacteria, and it is very meaningful to give antibacterial properties to the dental prosthesis itself.

この抗菌性を高める抗菌処理又は抗菌性組成物としては無機系及び有機系、また有機系でも第四アンモニウム塩系のものをはじめ多くのものがある。その中で、チタンを医療用途に用いる場合の抗菌剤として、特許文献2に、第四アンモニウム塩系のシラン化合物であるオクタデシルジメチルアンモニウムクロライドを用いる例が開示されている。すなわち、オクタデシルジメチルアンモニウムクロライドを蒸留水、アセトン、エーテル等の適当な溶媒に希釈した溶液に浸漬処理する抗菌処理方法が開示されている。また、特許文献3に、口腔内装置としてプラズマベースのイオン注入技術によりフッ素をイオン注入したチタンの例が開示されている。   There are many antibacterial treatments or antibacterial compositions that enhance antibacterial properties, including inorganic and organic types, and organic types such as those of quaternary ammonium salts. Among them, as an antibacterial agent when titanium is used for medical purposes, Patent Document 2 discloses an example using octadecyldimethylammonium chloride, which is a quaternary ammonium salt-based silane compound. That is, an antibacterial treatment method is disclosed in which octadecyldimethylammonium chloride is immersed in a solution diluted with an appropriate solvent such as distilled water, acetone, or ether. Patent Document 3 discloses an example of titanium ion-implanted with a plasma-based ion implantation technique as an intraoral device.

特開平05-7599号公報Japanese Patent Laid-Open No. 05-7599 特開2004-209241号公報JP 2004-209241 A 特開2004-504号公報JP 2004-504 Gazette

しかし、チタン又はチタン合金からなる医療用補綴部材の窒化処理又は表面の窒化チタン皮膜がどのような抗菌作用を有するかに関して開示されたものはない。特許文献1には、審美性を目的に黄金色の窒化チタン皮膜を得る方法は開示されているが、チタン皮膜の抗菌作用に関して何らの記載もない。また、特許文献2に開示された方法により処理されたチタンが抗菌性を有することの記載はあるが、それがどのようなチタン材料であるか不明であり、また、歯科医療用補綴部材として適切であるか明確でない。特許文献3に開示されたフッ素イオンを注入した純チタンはそれがどのような抗菌性を有するのか不明で、歯科医療用補綴部材として適切であるか明確でない。   However, there is no disclosure regarding the antibacterial action of the nitriding treatment of the medical prosthetic member made of titanium or a titanium alloy or the titanium nitride film on the surface. Patent Document 1 discloses a method for obtaining a golden titanium nitride film for the purpose of aesthetics, but there is no description regarding the antibacterial action of the titanium film. Further, although there is a description that titanium treated by the method disclosed in Patent Document 2 has antibacterial properties, it is unclear what kind of titanium material it is, and is suitable as a dental prosthetic member It is not clear whether it is. It is unclear what kind of antibacterial property pure titanium implanted with fluorine ions disclosed in Patent Document 3 is, and it is not clear whether it is suitable as a dental prosthetic member.

本発明は上記従来の問題点を明らかにし、抗菌性に優れ口腔内でも安全に使用することができる医療用補綴部材を提供することを目的とする。また、抗菌性に優れ口腔内でも安全に使用することができる医療用補綴部材の抗菌処理方法を提供することを目的とする。   An object of the present invention is to clarify the above-mentioned conventional problems, and to provide a medical prosthetic member that has excellent antibacterial properties and can be used safely even in the oral cavity. It is another object of the present invention to provide an antibacterial treatment method for a medical prosthetic member that has excellent antibacterial properties and can be used safely in the oral cavity.

本発明に係る抗菌性医療用補綴部材は、窒化チタン被膜を有するチタン又はチタン合金からなる。本発明において、窒化チタン被膜の厚さは、0.1μm以上とすることができる。   The antibacterial medical prosthetic member according to the present invention is made of titanium or a titanium alloy having a titanium nitride film. In the present invention, the thickness of the titanium nitride film can be 0.1 μm or more.

また、抗菌性医療用補綴部材は、窒化チタン被膜と、その上面にオクタデシルジメチルアンモニウムクロライド被膜とを有するチタン又はチタン合金からなる。   The antibacterial medical prosthetic member is made of titanium or a titanium alloy having a titanium nitride film and an octadecyldimethylammonium chloride film on the upper surface thereof.

また、本発明に係る抗菌性医療用補綴部材は、未処理のチタン又はチタン合金からなる医療用補綴部材に付着する菌数に対して、付着する菌数を1/3以下にすることができる抗菌性能を有する。特に、カンジダ アルビカンス菌(Candida albicans)又はストレプトコッカス ミュータンス菌(Streptococcus mutans)に対して有効な抗菌性を有するものである。   The antibacterial medical prosthetic member according to the present invention can reduce the number of bacteria attached to 1/3 or less of the number of bacteria attached to the medical prosthetic member made of untreated titanium or titanium alloy. Has antibacterial performance. In particular, it has effective antibacterial properties against Candida albicans or Streptococcus mutans.

本発明に係る医療用補綴部材の抗菌処理方法は、チタン又はチタン合金製の医療用補綴部材に、純チタンを蒸発源とし窒素ガスを処理ガスとして導入するイオンプレーティング処理を行うものである。   The antibacterial treatment method for a medical prosthetic member according to the present invention performs an ion plating treatment in which pure titanium is used as an evaporation source and nitrogen gas is used as a processing gas to a medical prosthetic member made of titanium or a titanium alloy.

また、純チタン又はチタン合金製の医療用補綴部材に、チタンを蒸発源とし窒素ガスを処理ガスとして導入するイオンプレーティング処理を行い、つぎに、オクタデシルジメチルアンモニウムクロライド水溶液中に浸漬処理を行うものである。   Also, a medical prosthesis member made of pure titanium or titanium alloy is subjected to ion plating treatment in which titanium is used as an evaporation source and nitrogen gas is used as a treatment gas, followed by immersion treatment in an octadecyldimethylammonium chloride aqueous solution. It is.

本発明に係る抗菌性医療用補綴部材又は抗菌処理方法は、抗菌性に優れ、医療用補綴部材として安全に使用することができ、特に、歯科医療用補綴部材として口腔内で安全に使用することができる。   The antibacterial medical prosthetic member or the antibacterial treatment method according to the present invention is excellent in antibacterial properties and can be used safely as a medical prosthetic member, and particularly used safely in the oral cavity as a dental prosthetic member. Can do.

以下、本発明に係る抗菌性医療用補綴部材の実施の形態について説明する。本発明に係る抗菌性医療用補綴部材は、窒化チタン被膜を有するチタン又はチタン合金からなる。すなわち、基地部分の材質はチタン又はチタン合金からなる。このチタン又はチタン合金は公知のもの、すなわち、入れ歯、インプラント,クラウン、ブリッジ,インレー,前装冠などに用いられているチタン又はチタン合金を使用することができる。   Hereinafter, embodiments of the antibacterial medical prosthetic member according to the present invention will be described. The antibacterial medical prosthetic member according to the present invention is made of titanium or a titanium alloy having a titanium nitride film. That is, the material of the base portion is made of titanium or a titanium alloy. As this titanium or titanium alloy, known ones, that is, titanium or titanium alloys used for dentures, implants, crowns, bridges, inlays, front crowns and the like can be used.

チタン表面に形成する窒化チタン皮膜は、どのような方法を用いて形成するものであってもよい。しかしながら、イオンプレーティング法によるものがよい。イオンプレーティング法による場合は、密着性の良い窒化チタン皮膜を形成することができる。   The titanium nitride film formed on the titanium surface may be formed using any method. However, an ion plating method is preferable. In the case of the ion plating method, a titanium nitride film with good adhesion can be formed.

窒化チタン被膜の厚さは0.1μm以上とすることができる。これにより、以下に説明する抗菌性試験において再現性の良い抗菌性医療用補綴部材を得ることができる。また、窒化チタン被膜の厚さは、以下に説明するオクタデシルジメチルアンモニウムクロライド水溶液中に浸漬し、抗菌性をさらに向上させる処理を行う場合には、0.3μm以上とするのがよい。これにより耐久性のある抗菌性医療用補綴部材を得ることができる。なお、窒化チタン被膜の厚さの上限は特に問わないが、経済性を考慮し数ミクロン以下とするのがよい。   The thickness of the titanium nitride film can be 0.1 μm or more. Thereby, an antibacterial medical prosthetic member having good reproducibility in the antibacterial test described below can be obtained. In addition, the thickness of the titanium nitride film is preferably 0.3 μm or more when immersed in an octadecyldimethylammonium chloride aqueous solution described below to perform a treatment for further improving antibacterial properties. Thereby, a durable antibacterial medical prosthetic member can be obtained. The upper limit of the thickness of the titanium nitride film is not particularly limited, but it is preferably set to several microns or less in consideration of economy.

また、本発明に係る抗菌性医療用補綴部材は、上記の窒化チタン被膜と、さらに、その上面にオクタデシルジメチルアンモニウムクロライド被膜とを有する。これにより一層抗菌性に優れた抗菌性医療用補綴部材を得ることができる。   Moreover, the antibacterial medical prosthetic member according to the present invention has the titanium nitride film described above and an octadecyldimethylammonium chloride film on the upper surface thereof. As a result, an antibacterial medical prosthetic member having further excellent antibacterial properties can be obtained.

オクタデシルジメチルアンモニウムクロライド被膜は、以下に説明するQAS処理により形成される皮膜の接触角測定試験で安定した皮膜が得られるものであればよい。   The octadecyldimethylammonium chloride film may be any film that provides a stable film in a contact angle measurement test of a film formed by the QAS treatment described below.

このような構成の抗菌性医療用補綴部材の抗菌性試験結果を図1に示す。図1は、株式会社ウィルコ社製の純チタン平ワッシャ(外径10.0、穴径4.5、板厚0.8mm)を表1に示す各処理をしたものにカンジダ アルビカンス菌を接種・培養後に形成されたバイオフィルムからATP量を測定した結果を示すグラフである。なお、上記純チタン平ワッシャは、歯科医療用補綴部材として用いられる純チタンと同等の抗菌性、安全性を有するものである。   The antibacterial test result of the antibacterial medical prosthetic member having such a configuration is shown in FIG. Fig. 1 shows the result of inoculating and culturing Candida albicans on pure titanium flat washers (outer diameter 10.0, hole diameter 4.5, plate thickness 0.8mm) manufactured by Wilco Co., Ltd. It is a graph which shows the result of having measured the amount of ATP from the biofilm. The pure titanium flat washer has antibacterial properties and safety equivalent to pure titanium used as a dental prosthesis member.

図1において、横軸は表1に示す試験片番号を示し、縦軸はATP量を示す。ATP量とは、下記に説明する抽出液1リットル当たりのアデノシン三リン酸のモル濃度(nmol)を示す。表1において、QAS処理とは、オクタデシルジメチルアンモニウムクロライド水溶液に浸漬する処理をいう。接触角とはヤングの接触角をいい、接触角測定試験片の表面に10μlの蒸留水を滴下して測定した。   In FIG. 1, the horizontal axis indicates the test piece number shown in Table 1, and the vertical axis indicates the ATP amount. The amount of ATP indicates the molar concentration (nmol) of adenosine triphosphate per liter of the extract described below. In Table 1, QAS treatment refers to treatment immersed in an aqueous solution of octadecyldimethylammonium chloride. The contact angle is Young's contact angle, which was measured by dropping 10 μl of distilled water on the surface of a contact angle measurement specimen.

図1によると、試験片番号1(未処理)の場合のATP量が4.9nmol/lであるのに対し、試験片番号2(窒化処理)の場合はATP量が2.8nmol/lとなっており、付着カンジダ アルビカンス菌は未処理の場合の57%になっていることが分かる。また、試験片番号3(QAS処理)の場合はATP量が2.1nmol/lで、付着カンジダ アルビカンス菌は未処理の場合の43%になっており、試験片番号4(窒化処理及びQAS処理)の場合はATP量が1.5nmol/lで、付着カンジダ アルビカンス菌は未処理の場合の31%になっていることが分かる。すなわち、窒化処理及びQAS処理をすることにより、未処理のもの(試験片番号1)に対して付着する菌を1/3以下にすることができる。   According to FIG. 1, the ATP amount in the case of test piece number 1 (untreated) is 4.9 nmol / l, whereas in the case of test piece number 2 (nitriding treatment), the ATP amount is 2.8 nmol / l. It can be seen that adhering Candida albicans is 57% of the untreated case. In the case of test piece number 3 (QAS treatment), the ATP amount was 2.1 nmol / l, and the number of adhering Candida albicans was 43% of that in the case of no treatment, and test piece number 4 (nitriding treatment and QAS treatment). In the case of ATP, the amount of ATP is 1.5 nmol / l, and the attached Candida albicans bacteria is 31% of the untreated case. That is, by performing nitriding treatment and QAS treatment, it is possible to reduce 1/3 or less of the bacteria attached to the untreated one (test piece number 1).

上記の抗菌性試験で用いたカンジダ アルビカンス菌は、人体内に常在し適当な環境で容易に増殖するものであるから、歯科医療用補綴部材の抗菌性試験に好適であり、しかも特性の異なる菌糸型と酵母型の菌種を有するため抗菌効果を調べるのに好適である。   Candida albicans used in the above antibacterial test is suitable for an antibacterial test of dental prosthetic members because it is resident in the human body and easily proliferates in an appropriate environment, and has different characteristics. Since it has a mycelium type and a yeast type, it is suitable for examining the antibacterial effect.

また、本抗菌性試験は、抗菌性をATP量で判定している。この方法は、定量性に優れ、しかも定量限界が広いので抗菌性能を高精度で測定・比較することができる。例えば、カンジダ アルビカンス菌の場合、数個から1000万個までの細菌数を測定することができる。   In this antibacterial test, antibacterial properties are determined by the amount of ATP. This method is excellent in quantification and has a wide quantification limit, so that antibacterial performance can be measured and compared with high accuracy. For example, in the case of Candida albicans, the number of bacteria from several to 10 million can be measured.

Figure 0004945743
Figure 0004945743

上記抗菌性試験に用いた試験片の作成、ATP量の測定は以下のように行った。まず、本抗菌性試験に用いた試験片の窒化処理又は窒化チタン膜の形成は以下のように行った。すなわち、イオンプレーティング装置のチャンバー内圧力を1×10-4Pa、チャンバー内温度を288℃にして純度99%の純チタンを蒸発させ、純チタン平ワッシャの表面上に薄いチタン膜を形成させた後、窒素ガスを導入して窒化チタンを蒸着させて膜厚0.5μmの窒化チタン膜を形成させた。窒化チタンを蒸着時のチャンバー内圧力は5×10-3Pa、ビーム電流は170A、ビーム電圧は25Vであった。なお、処理開始からチタン膜形成までの純チタン平ワッシャに負荷するバイアス電圧は95V、窒化チタン膜形成時のバイアス電圧は30Vで、処理後のチャンバー内温度は313℃であった。なお、上記窒化チタン膜の形成において、先ず純チタン平ワッシャの表面上に薄いチタン膜を形成させるのは、これにより窒化チタン膜の密着性をよくするためである。 Preparation of the test piece used for the antibacterial test and measurement of the ATP amount were performed as follows. First, nitriding treatment of a test piece used in this antibacterial test or formation of a titanium nitride film was performed as follows. That is, the pressure in the chamber of the ion plating apparatus is 1 × 10 −4 Pa, the temperature in the chamber is 288 ° C., 99% pure titanium is evaporated, and a thin titanium film is formed on the surface of the pure titanium flat washer. After that, nitrogen gas was introduced to deposit titanium nitride to form a titanium nitride film having a thickness of 0.5 μm. When depositing titanium nitride, the pressure inside the chamber was 5 × 10 −3 Pa, the beam current was 170 A, and the beam voltage was 25V. The bias voltage applied to the pure titanium flat washer from the start of the treatment to the formation of the titanium film was 95 V, the bias voltage at the time of forming the titanium nitride film was 30 V, and the temperature in the chamber after the treatment was 313 ° C. In the formation of the titanium nitride film, the thin titanium film is first formed on the surface of the pure titanium flat washer in order to improve the adhesion of the titanium nitride film.

次に、試験片のQAS処理又はオクタデシルジメチルアンモニウムクロライド被膜の形成は以下のように行った。すなわち、まず、蒸留水中にチッソ株式会社製のオクタデシルジメチルアンモニウムクロライドを希釈し、水に対する容量%が5%となるオクタデシルジメチルアンモニウムクロライド水溶液を作製した。ついで、室温中でこの溶液に、購入した純チタン平ワッシャ又は上記窒化チタン皮膜を形成させたものを30分間浸漬した。浸漬時間は予め接触角が80〜90°になる条件から30分とした。試験片の浸漬処理後は、純水で洗浄後乾燥させた。乾燥後試験片表面に形成された皮膜の質量を測定したところ試験片の単位面積当たり0.35〜0.4μg/cm2であった。 Next, the QAS treatment of the test piece or the formation of the octadecyldimethylammonium chloride film was performed as follows. That is, first, octadecyldimethylammonium chloride manufactured by Chisso Corporation was diluted in distilled water to prepare an octadecyldimethylammonium chloride aqueous solution having a volume% with respect to water of 5%. Subsequently, the purchased pure titanium flat washer or the one formed with the titanium nitride film was immersed in this solution for 30 minutes at room temperature. The immersion time was set to 30 minutes from the condition that the contact angle was 80 to 90 ° in advance. After the immersion treatment of the test piece, it was washed with pure water and dried. When the mass of the film formed on the surface of the test piece after drying was measured, it was 0.35 to 0.4 μg / cm 2 per unit area of the test piece.

オクタデシルジメチルアンモニウムクロライドは水溶媒に希釈するのがよい。通常行われているように有機溶媒中に希釈する場合は、時間経過により粘度が高くなり、オクタデシルジメチルアンモニウムクロライド膜を均質に形成させるのが困難になる。   Octadecyldimethylammonium chloride is preferably diluted in an aqueous solvent. When it is diluted in an organic solvent as is usually done, the viscosity increases with time, and it becomes difficult to form an octadecyldimethylammonium chloride film uniformly.

試験片へのカンジダ アルビカンス菌の接種・培養は以下のように行った。すなわち、上記各処理を経た平ワッシャ上に1.0×107cfu/mlに調整したカンジダ アルビカンスの菌液50μLを接種し、これを37℃の恒温槽内で2時間保温した。その後、サブロー培地2mlを加え、37℃の恒温槽内で48時間培養した。培養後、平ワッシャ表面の余剰な菌を水洗・除去した。 The test piece was inoculated and cultured with Candida albicans as follows. That is, 50 μL of Candida albicans bacterial solution adjusted to 1.0 × 10 7 cfu / ml was inoculated on the flat washer subjected to each of the above treatments, and this was incubated for 2 hours in a 37 ° C. constant temperature bath. Thereafter, 2 ml of Sabouraud medium was added, and the cells were cultured for 48 hours in a 37 ° C. constant temperature bath. After culturing, excess bacteria on the surface of the flat washer were washed and removed.

上記培養操作により平ワッシャ表面に形成されたバイオフィルムから以下のようにしてATP量を測定した。まず、得られたバイオフィルムを500μlの東亜電波工業株式界社製微生物用ATP抽出試薬AF-2K1に浸漬し、室温にて30分間抽出した。その後その抽出液をチューナーバイオシステム社製セルタイマーグローにセットしてATP量を測定した。   The amount of ATP was measured as follows from the biofilm formed on the surface of the flat washer by the culture operation. First, the obtained biofilm was immersed in 500 μl of ATP extraction reagent AF-2K1 for microorganisms manufactured by Toa Denpa Kogyo Co., Ltd. and extracted at room temperature for 30 minutes. Thereafter, the extract was set on a cell timer glow manufactured by Tuner Biosystems, and the amount of ATP was measured.

上記抗菌性試験で用いた窒化処理をしたもの(試験片番号2)及び窒化処理とQAS処理をしたもの(試験片番号4)と同等な試験片を用いて、熱サイクル試験を行った。熱サイクル試験とは、上記試験片を容量3lの4℃と60℃の水槽にそれぞれ1分ずつ交互に漬け、これを所定回数繰り返し、その熱サイクルの影響を調べる試験をいう。本熱サイクル試験においては熱サイクルを20000回繰り返した。熱サイクルの試験の影響は、熱サイクル試験が終わったものを上記カンジダ アルビカンス菌の接種・培養を行った後、抗菌性試験を行って調べた。抗菌性試験の結果は、いずれの試験片においても全く熱サイクル試験を経なかった図1の結果と変わらなかった。上記熱サイクルの20000回は、歯科医療用補綴部材として1年間の使用試験に相当するものであり、本発明に係る抗菌性医療用補綴部材は、歯科医療用補綴部材として十分実用可能な耐久性を有することが分かる。   A thermal cycle test was performed using a test piece equivalent to the nitriding treatment (test piece number 2) and the nitriding and QAS treatment (test piece number 4) used in the antibacterial test. The thermal cycle test refers to a test in which the test piece is immersed alternately in a 3 liter water tank of 4 ° C. and 60 ° C. for 1 minute each, and this is repeated a predetermined number of times to examine the influence of the thermal cycle. In this thermal cycle test, the thermal cycle was repeated 20000 times. The effect of the heat cycle test was examined by inoculating and culturing the above-mentioned Candida albicans bacteria after the heat cycle test was completed, and then conducting an antibacterial test. The result of the antibacterial test was not different from the result of FIG. 1 which did not pass any thermal cycle test in any test piece. The thermal cycle of 20000 corresponds to a one-year use test as a dental prosthetic member, and the antibacterial medical prosthetic member according to the present invention has a durability that is sufficiently practical as a dental prosthetic member. It can be seen that

QAS処理が人体に対して安全か否かを調べるための毒性試験を行った。毒性試験は以下の亜急性毒性試験により行った。すなわち、日本チャールズリバー株式会社より購入したCharles River CD-1マウス(雄6匹、雌6匹、共に生後5週齡)を、オクタデシルジメチルアンモニウムクロライド投与群(雄3匹、雌3匹)と、オクタデシルジメチルアンモニウムクロライドを投与しないコントロール群(雄3匹、雌3匹)とに分け、2〜3日おきに体重測定を行った。オクタデシルジメチルアンモニウムクロライドの投与は、3匹のマウス/1ケージ当たり1μlのオクタデシルジメチルアンモニウムクロライドの原液/200ml水となるよう添加したものを飲料水として毎日与え、一週間に一度、新鮮なものと交換した。なお、オクタデシルジメチルアンモニウムクロライドの原液はモル濃度で70%のメタノール溶液のものを使用した。   Toxicity tests were conducted to determine whether QAS treatment is safe for the human body. The toxicity test was conducted by the following subacute toxicity test. That is, Charles River CD-1 mice (6 males, 6 females, both 5 weeks old), purchased from Japan Charles River Co., Ltd., and octadecyldimethylammonium chloride administration group (3 males, 3 females), It was divided into a control group (3 males and 3 females) not administered with octadecyldimethylammonium chloride, and body weight was measured every 2-3 days. The administration of octadecyldimethylammonium chloride is given as drinking water every day for 3 mice, 1 μl of octadecyldimethylammonium chloride stock / 200 ml water added per cage, and replaced with fresh one a week. did. The stock solution of octadecyldimethylammonium chloride was a 70% methanol solution in molar concentration.

上記試験結果を図2に示す。図2において、横軸は経過日数を示し、縦軸はマウスの体重を示す。パラメータは、control♂が雄のコントロール群、control♀が雌のコントロール群、QAS♂が雄のオクタデシルジメチルアンモニウムクロライド投与群、QAS♀が雌のオクタデシルジメチルアンモニウムクロライド投与群である。   The test results are shown in FIG. In FIG. 2, the horizontal axis indicates the number of days elapsed, and the vertical axis indicates the weight of the mouse. The parameters are the control group for male control group, control group for female control group, QAS class for male octadecyldimethylammonium chloride administration group, and QAS class for female octadecyldimethylammonium chloride administration group.

図2によると、いずれのマウスも体重変化はほとんどない。また、雄及び雌についてオクタデシルジメチルアンモニウムクロライド投与群とコントロール群とも体重変化の状態に差異はないことが分かる。すなわち、本発明に係る抗菌性医療用補綴部材は、歯科医療用補綴部材として十分実用可能な安全性を有することが分かる。   According to FIG. 2, there is almost no weight change in any mouse. Moreover, it can be seen that there is no difference in the state of weight change between the octadecyldimethylammonium chloride administration group and the control group for males and females. That is, it can be seen that the antibacterial medical prosthetic member according to the present invention has sufficient safety for practical use as a dental prosthetic member.

以上、本発明の実施の形態について説明した。しかし、本発明は上記の実施例に限らない。例えば、純チタン製の歯科医療用補綴部材に限らず通常使用されるチタン合金製の歯科医療用補綴部材にも好適に使用することができる。また、本発明に係る抗菌性医療用補綴部材は、ストレプトコッカス ミュータンス菌についても上記と同様な抗菌性、耐久性及び安全性を有している。すなわち、本発明にかかる抗菌性医療用補綴部材は、未処理の、すなわち通常用いられるチタン又はチタン合金からなる歯科医療用補綴部材に付着するカンジダ アルビカンス菌又はストレプトコッカス ミュータンス菌の菌数に対して、付着する菌数を1/3以下にすることができる抗菌性能を有する。そして、このような抗菌性医療用補綴部材は、歯科医療に限らず他の医療分野で使用される補綴部材にも使用することができる。   The embodiment of the present invention has been described above. However, the present invention is not limited to the above embodiments. For example, the present invention can be suitably used not only for a pure titanium dental prosthetic member but also for a titanium alloy dental prosthetic member that is normally used. The antibacterial medical prosthetic member according to the present invention has the same antibacterial properties, durability and safety as described above for Streptococcus mutans. That is, the antibacterial medical prosthetic member according to the present invention is an untreated, that is, against the number of Candida albicans or Streptococcus mutans adhering to a dental prosthetic member made of titanium or a titanium alloy that is usually used. It has antibacterial performance that can reduce the number of attached bacteria to 1/3 or less. And such an antibacterial medical prosthetic member can be used not only for dentistry but also for prosthetic members used in other medical fields.

各処理におけるATP量を示すグラフである。It is a graph which shows the amount of ATP in each process. 毒性試験におけるマウスの体重の変化状態を表すグラフである。It is a graph showing the change state of the body weight of a mouse | mouth in a toxicity test.

Claims (3)

チタン又はチタン合金製の医療用補綴部材に窒化チタン被膜を形成し、その窒化チタン被膜の上面にオクタデシルジメチルアンモニウムクロライド被膜を形成させることにより抗菌処理を行う医療用補綴部材の抗菌処理方法。An antibacterial treatment method for a medical prosthesis member in which an antibacterial treatment is performed by forming a titanium nitride coating on a titanium or titanium alloy medical prosthetic member and forming an octadecyldimethylammonium chloride coating on the upper surface of the titanium nitride coating. カンジダアルビカンス菌又はストレプトコッカス ミュータンス菌に対して抗菌処理を行う請求項1に記載の医療用補綴部材の抗菌処理方法 The antibacterial treatment method of the medical prosthetic member according to claim 1, wherein the antibacterial treatment is performed on Candida albicans or Streptococcus mutans. チタン又はチタン合金製の医療用補綴部材に、純チタンを蒸発源とし窒素ガスを処理ガスとして導入するイオンプレーティング処理を行い、つぎに、オクタデシルジメチルアンモニウムクロライド水溶液中に浸漬処理を行うことを特徴とする医療用補綴部材の抗菌処理方法。   A medical prosthetic member made of titanium or a titanium alloy is subjected to ion plating treatment in which pure titanium is used as an evaporation source and nitrogen gas is used as a treatment gas, and then immersed in an aqueous solution of octadecyldimethylammonium chloride. An antibacterial treatment method for a medical prosthetic member.
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US10813847B2 (en) 2015-10-30 2020-10-27 University Of Florida Research Foundation, Inc. Dielectric coatings for fixed and removable oral prosthetic restorations
WO2020028596A1 (en) * 2018-07-31 2020-02-06 University Of Florida Research Foundation Quarternized titanium-nitride anti-bacterial coating for dental implants
US20210228323A1 (en) * 2018-07-31 2021-07-29 University Of Florida Research Foundation Quarternized titanium-nitride anti-bacterial coating for dental implants
US11864964B2 (en) 2018-07-31 2024-01-09 University Of Florida Research Foundation, Inc. Quarternized titanium-nitride anti-bacterial coating for dental implants

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