JP2014221273A - 表面上にパラジウムを含む金属粒子を有する電子供与表面を有する生体適合性基体 - Google Patents
表面上にパラジウムを含む金属粒子を有する電子供与表面を有する生体適合性基体 Download PDFInfo
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Abstract
【解決手段】生体適合性の基体の使用であって、フィブリノーゲン吸着を低下させること、組織内殖を向上させること、C3a及びC3b活性化を低下させること、炎症反応を低下させること、血液凝固を向上させること、の少なくも1つのための使用であり、前記生体適合性の基体は電子供与表面を有し、前記電子供与表面は銀を含み、前記表面上に金属粒子が存在し、前記金属粒子がパラジウム及び金を含み、前記金属粒子の量は0.001〜8μg/cm2であり、前記金属粒子は前記電子供与表面上に分散された粒子であり、前記金属粒子は被覆層を形成していない基体の使用。
【選択図】なし
Description
本発明は、反復可能および制御された様式で生体適合性に関する表面特性を修飾(又は改変:modify)することを可能とするナノ粒子を有する新規な基体に関する。修飾されうる表面特性の例としては、これらに限定されないが、疎水性、タンパク質吸着、組織内殖、補体活性化、炎症反応、血栓形成性、摩擦係数、および表面の硬さが挙げられる。本発明はさらに、新規な基体を含む物(又は対象物:object)にも関する。本発明はさらに基体の使用に関する。最後に、本発明はさらにかかる基体の製造方法にも関する。
有用な特性を達成するように表面特性を修飾することが常に望まれてきた。特に、生体適合性の物(又は対象物)に関して重要である表面特性を修飾することを可能にすることが望まれている。様々な目的での既知の表面修飾の例を以下に記載する。
表面に関する技術水準における問題は、生体適合性であって、疎水性、タンパク質吸着、組織内殖、補体活性化、炎症反応、血栓形成性、摩擦係数、および表面硬さを反復可能に改変することが出来る、表面の提供方法である。
(定義)
本発明を詳細に開示および記載する前に、本発明は本明細書に開示された特定の配置、方法の工程および材料に限定されず、かかる配置、方法の工程および材料はいくらか変動しうることを理解されたい。また本明細書において用いる用語は、特定の態様を記載する目的でのみ用いられており、限定の意図はないことを理解されたい。本発明の範囲は添付の請求の範囲およびその均等物にのみ限定されるからである。
本発明によると、基体は所望の特性を示すよう処理される。基体は広範な材料から構成されうる。一つの態様において、基体は電子供与表面を有する材料から構成される。別の態様において、それは電子供与表面を有さない材料から構成される。電子供与表面の場合、金属粒子を電子供与表面に直接適用してもよい。表面が電子供与性でない場合、電子供与材料の層を適用して、電子供与表面を作らなければならない。
1.前処理
2.すすぎ
3.活性化
4.電子供与表面の析出
5.すすぎ
6.金属粒子の析出
7.すすぎ
8.乾燥。
1.すすぎ
2. 金属粒子の析出
3.すすぎ
4.乾燥。
金属粒子の量の関数としての表面の疎水性
銀の均一な層を以下の方法にしたがってガラス基体上に析出させた。基体をクロム酸洗浄溶液に5 分間58℃で浸漬し、次いで脱塩水ですすいだ。基体表面を塩化第一スズ水溶液中での浸漬により活性化し、次いで脱塩水ですすいだ。基体表面を次いで銀イオンを含む3 析出溶液中での浸漬により銀の均一な層でめっきした(plate)。これにより約 115Åの厚さに対応する適用量1.2μg/cm2の銀表面が得られた。23% パラジウムおよび77% 金からなる粒子を次いで第一の銀表面上に金/パラジウムの金属粒子を含む希釈懸濁液中への浸漬により析出させた。金属粒子の懸濁液を金塩およびパラジウム塩を還元剤で還元し、 懸濁液を安定化剤で安定化させることにより作った。基体を次いで脱塩水ですすぎ、乾燥させた。
金属粒子の量の関数としてのタンパク質吸着
銀の均一な層を二酸化ケイ素基体上に析出させた。基体を20% 硫酸洗浄溶液に10 分間 室温で浸漬し、次いで脱塩水ですすいだ。基体表面を塩化第一スズ水溶液への浸漬により活性化し、脱塩水ですすいだ。基体表面を次いで銀イオンを含む析出溶液の4 浴に浸漬することにより銀の均一な層でめっきした。これにより約 77Åの厚さに対応する0.8 μg/cm2の適用量を有する銀表面が得られた。95% パラジウムおよび5% 金からなる粒子を次いでPd/Au-粒子の希釈懸濁液への浸漬により第一の銀表面上に析出させた。金属粒子の適用量はそれぞれ0.05、0.12、0.48および0.59 μg/cm2であった。基体を脱塩水ですすぎ、乾燥させた。
ポリエステル繊維の網をまず5% 水酸化カリウム 溶液で、5分間、30℃ですすいだ。脱塩水中で繰り返しすすいだ後、基体を1 g/l 塩化第一スズの酸性溶液に室温で10分間浸漬した。脱塩水ですすいだ後、それを2 g/l 硫酸銅、5 g/l 水酸化ナトリウム、50 g/l クエン酸ナトリウムおよび0.005 ml/l ホルムアルデヒドを含むめっき浴に10分間35℃で浸漬した。約 200Åの銅層が得られ、脱塩水で新たにすすいだ後、基体をそれぞれ0.05 g/lのパラジウム粒子および金粒子を含む粒子懸濁液に浸漬した。金属粒子の適用量は0.4 μg/cm2であった。
PMMA の基体を5% 塩酸で 2 分間清浄にし、次いで脱塩水ですすいだ後、0.02 g/l のスズイオンを含むpH2.5の溶液に浸漬した。すすいだ後、基体を0.005 g/lの銀イオン、0.02 ml/l アンモニア、0.05 g/l 水酸化カリウムおよび 0.0005 ml/l ホルムアルデヒドを含む溶液に5 分間室温で浸漬した。これにより0.12 μg/cm2 の銀を有する表面が得られた。すすいだ後、それを0.005 g/l パラジウム および0.002 g/l 金粒子を含む粒子懸濁液に浸漬した。金属粒子の適用量は0.05 μg/cm2であった。
不織ポリイミド基体をNaOH の12% 溶液に40℃で 10 分間浸漬した。脱塩水で繰り返しすすいだ後、それを0.5 g/l 塩化第一スズを含むアルコール溶液に5 分間室温で浸漬した。すすいだ後、それを実施例 3にしたがって銅浴に浸漬した。2 μg/cm2の銅層が得られた。すすいだ後、それを懸濁液の総重量に対して計算して1% のPdおよび0.2%の金粒子を含む懸濁液に浸漬した。金属粒子の適用量は0.6 μg/cm2であった。
ナイロン繊維を5% NaOHで10 分間40℃で清浄にし脱塩水ですすいだ後、pH 2.2の 0.6 g/l 塩化第一スズ溶液に15 分間室温で浸漬した。この後、表面は0.8 μg/cm2の銀量を含んでいた。新たにすすいだ後、それを実施例 2にしたがって銀浴に浸漬し、 新たにすすいだ後、1% Pdおよび0.05% Au 粒子を含む懸濁液に浸漬した。金属粒子の適用量は0.12 μg/cm2であった。
アルミニウムの基体を10% 硝酸および3% フッ化水素酸の溶液中で、60℃で20 分間処理した。すすいだ後、基体を3 g/l 塩化第一スズの酸性溶液に浸漬し、新たに すすいだ後、実施例 2による銀浴に浸漬した。この工程の後、約80Åの銀量が表面上に得られた。さらにすすいだ後、基体を1% Pdおよび2% Au 粒子を含む懸濁液に浸漬した。金属粒子の適用量は0.7 μg/cm2であった。
PTFEの基体を水酸化ナトリウム水溶液中で5 分間エッチング処理した。すすぎおよび乾燥の後、それを 0.7 g/l 塩化第一スズを含む溶液に20 分間室温で浸漬した。基体をすすいだ後、0.2 g/l 硝酸銀、0.5 ml/l アンモニアおよび水酸化ナトリウムを含む pH 10.5のめっき浴に5 分間浸漬した。この工程の後約 2.2 μg/cmの銀量が表面上に得られた。新たにすすいだ後、それを3% Pd および0.1% Au 粒子を含む懸濁液に5 分間室温で浸漬した。金属粒子の適用量は0.03 μg/cm2であった。
ガラスプレートを10% 硫酸 および1% フッ化水素酸で、室温で15 分間すすいだ。すすいだ後、それを1% フッ化スズ 溶液に浸漬し、 新たにすすいだ後、実施例 2による銀浴に浸漬した。この工程の後、約140Åの銀量が表面上に得られた。新たにすすいだ後それを1% ルテニウムおよび2% パラジウム 粒子を含む懸濁液に浸漬した。金属粒子の適用量は0.25 μg/cm2であった。
ステンレス鋼基体を15% 硝酸および5% HFの溶液に室温で30 分間浸漬し、次いで脱塩水ですすいだ。実施例 11の工程にしたがってプロセスを続けた。金属粒子の適用量は0.9 μg/cm2であった。
チタンの棒を18% 硝酸および2% HFの溶液 で20 分間室温で清浄にした。電子供与表面の適用および金属粒子の適用を実施例 11のように行った。金属粒子の適用量は0.6 μg/cm2であった。
散逸をモニターする石英結晶微量天秤 (QCM-D)による、表面に誘導される補体活性化の検出
異物反応の定量を表面に結合した補体因子 C3bに対するウサギ-抗ヒト抗体の結合をモニターすることによって間接的に達成する。
表面の調製
モデル表面として、標準的な QCM-D結晶にAu (s)、Ti (s)をスパッタしたもの (それぞれQSX301 および QSX310)を用いた。実施例 2に記載の方法を用いて、標準的な SiO2 QCM-D 結晶 (QSX 303、Q-Sense Sweden)上に、本発明に係る被覆を適用した。
我々は5名の健康なドナー(Sahlgrenska University Hospital、Geoteborg、Sweden)から新鮮な全血を受け取った。血液を室温でおよそ 4 時間凝固させて補体活性血清を得た。血清を次いで4000 rpmで20 分間遠心分離し(Hettich Universal 16 R)、その後上清を取り出し、上記のように再遠心分離し、-70℃で保存した。
上記のように被覆したSiO2 表面は0.35-0.61 μg/cm2の量の銀を有していた。粒子における金の量は以下の表に示すように変動しており、補体活性化は表に示すように測定された。
バイオマテリアル表面上での血小板付着および可溶性補体因子 C3a産生
バイオマテリアルに曝された新鮮な全血における血小板の消費を用いて、所望のバイオマテリアルの血栓形成性を定量する。さらに、活性化補体因子 3の可溶性画分(C3a)を用いてバイオマテリアル表面からの補体活性化をモニターする。
血小板(plateletまたはthrombocytes)は、健康な血液に通常存在する小皿状の無核細胞断片である。それらは血管壁の保全に重要な役割を果たし、損傷領域に動員され、活性化されて栓を形成し、出血および血液損失を防ぐ。血小板は特定のバイオマテリアル表面に付着し、活性化され、望ましくない、危険である可能性のある凝血塊を形成することがあることも知られている。
実験チャンバ
実験チャンバは簡単にはPMMA 顕微鏡スライドに接着する2つのPMMA環から構成され、2つのウェルを構築する。全血の添加後、試験すべき材料を2つのウェルの上の蓋として配置し、クリップにより適切な位置に保持する。チャンバを次いで37℃の水中で60 分間22 rpmで回転する皿にマウントする。
血液を1名の健康なドナーから得、可溶性ヘパリン (Leo Pharma)を含む2x ヘパリン処置バイアルに回収し、終濃度1.0 IU ヘパリン/mlとした。収集した血液を次いですぐに実験チャンバに移した。
実験チャンバ中でのインキュベーションの後、血液を EDTA (Fluka)に添加し、終濃度 4mMとした。血小板を次いでCoulter AcT diffTM (Coulter Corporation) 自動細胞計数装置で計数した。
血小板計数の後、血液を4600 gで10 分間+4℃で遠心分離し、上清 (血漿)を保存し、-70℃で測定時まで貯蔵した。
実施例 2に示す方法にしたがってガラス上に製造された被覆された対象物の銀表面濃度は約 1.3 μg/cm2であった。
炎症反応の測定
材料
NHSp-2 (Immunologisk institutt、Rikshospitalet、Oslo 、Norwayからの正常ヒト血清プール)、健康血液ドナーからの血清。
1)血清を氷上に置いた。
2)ゼロサンプルを除いた。750μlを15μl EDTA 0,5Mを有するチューブに直接添加した。サンプルを氷上で維持した。
3)750 μl 血清を各チューブに添加した。
4)チューブをローター( 5 rpm)に37℃で取り付け、30 分間インキュベートした。
5)血清をピペットで取り出し、15μl EDTA 0.5Mを有するチューブに添加した。サンプルを氷上に置き、TCC (可溶性末端 C5b-9 補体複合体)について分析した。
Mollnes TE、Lea T、Froeland SS、Harboe M. “Quantification of the terminal complement complex in human plasma by an enzyme-linked immunosorbent assay based on monoclonal antibodies against a neoantigen of the complex”、Scand J Immunol 22:197-202. 1985その後以下の文献で改変されたものである:
Mollnens TE, Redl H、Hoegaesen K、Bengtsson A、Garred P、Speilberg L、Lea T、Oppermann M、Goetze O、Schlag G.“Complement activation in septic baboons detected by neoepitope specific assays for C3b/iC3b/C3c、C5a and the terminal C5b-9 complement complex (TCC)”、Clin Exp Immunol 91:295-300. 1993。
銀表面濃度の量は1μg/cm2であった。
インビトロおよびインビボでの細胞接着
初代正常ヒト皮膚線維芽細胞 (NHDF、Karocell Tissue Engineering AB、Stockholm、Sweden)、継代7を用いた。細胞をDMEM+GlutaMAX(商標)-1 (Gibco、UK)、10% 胎児ウシ血清 (FBS、Gibco、UK) および 1% 抗生物質-抗真菌剤 (Gibco、UK)を含む完全線維芽細胞培地中で、組織培養フラスコで37℃、5% CO2および湿度95%にて培養した。二酸化ケイ素の10種類の基体を実施例 2に記載の方法にしたがって被覆し、無菌的にパンチで直径15 mmのディスクとし、24-ウェルプレートに適合させた。ディスクを無菌 PBS (リン酸緩衝食塩水、Gibco、UK)に浸漬し、1 mlの細胞懸濁液 (17000 細胞/ml)を二酸化ケイ素ディスクおよび空のPS-ウェル(ポリスチレン、Falcon、BD Biosciences、Belgium)に播き、24時間および72時間三連でインキュベートした。すべてのサンプルからの培地を回収し、400gで、5 分間遠心分離し、-70℃で保存した後、細胞放出因子のELISA (酵素結合免疫吸着測定法) 分析を行った。各材料につき2つのディスクを完全培地とともに細胞無しでインキュベートし、バックグラウンド値を評価した。
表面および周囲の培地に付随している細胞量をNucleoCounter(登録商標)-システム (ChemoMetec A/S、Denmark)によって測定した。簡単に説明すると、細胞を溶解緩衝液および安定化緩衝液(システムに備えられている)で処理した。溶解したサンプルを、細胞核を染色する蛍光ヨウ化プロピジウムであらかじめ被覆したNucleoCassette(商標)にロードし、NucleoCounter(登録商標)で定量した。
細胞生存度を、細胞膜損傷のマーカーである培地中の乳酸デヒドロゲナーゼ含量(LDH)を、ピルビン酸から乳酸のLDH媒介変換の分光光度的評価を用いて (C-Laboratory、Sahlgrenska University Hospital、Goeteborg、Sweden)測定することにより判定した。
TGF-β1 (トランスフォーミング増殖因子ベータ1) およびI型コラーゲンの量をELISAキット (Human TGF-β1、Quantikine(登録商標)、R&D Systems、UK; Human collagen type1 ELISA KIT、Cosmo Bio Co.、Japan)により 製造業者の指示にしたがってSpectraVmax ELISA リーダー (Molecular Devices、UK)にて検出した。
6種類の二酸化ケイ素の基体(直径10 mm)を実施例 2に記載の方法を用いて被覆し、滅菌した。標準的 ペレット餌および水を与えた雌性スプラーグドーリーラット(200-250 g)を、2,7% イソフルランおよび空気の混合物(Univentor 400 Anaesthesia Unit、Univentor、Malta)で麻酔し、0.01 mg Temgesicを鎮痛剤として皮下に手術前に与えた。ラットを剪毛し、 70% エタノール中の5 mg/ml クロロヘキシジンで清浄にし、各ラットにそれぞれのインプラントタイプの1つを背中の皮下に(s.c.)与えた。創傷は2 縫合糸 (Ethilon 5-0 FS-3、Ethicon(登録商標)、Johnson & Johnson、Belgium)で閉じた。植え込み期間は初期炎症プロセスの評価のためには1および3日間であり、線維性カプセル形成および後期炎症反応の調査のためには21 日間であった (n=8 ラット/期間)。外植を行った際に、動物を2,7% イソフルランと空気の混合物による短い麻酔の後にペントバルビタール (60 gL-1)の過剰用量により屠殺した。インプラントおよび周囲の滲出液を回収した。滲出細胞をHBSS (ハンクス平衡塩溶液、Gibco、UK) の繰り返しの吸引によりポケットから得、氷上に維持した。滲出液を400gで、5 分間遠心分離し、上清を-70℃で維持した。すべての植え込み研究はLocal Ethical Committee for Laboratory Animalsにより認可されたものであった。
滲出液中の細胞の濃度およびタイプ(細胞/ml)をTurk染色によりBurker チャンバ中で光学顕微鏡により計数し、遠心分離した滲出液中およびインプラント上の細胞量をNucleoCounter(登録商標)-システムにより判定した。
細胞生存度は光学顕微鏡を用いたトリパンブルー排除およびLDH 評価 (C-Laboratory、Sahlgrenska University Hospital、Goteborg、Sweden)により判定した。
TGF-β1 (トランスフォーミング増殖因子ベータ1)およびMCP-1 (単球化学誘引物質 タンパク質-1) の量をELISAキット(Rat TGF-β1、Quantikine(登録商標)、R&D Systems、UK; Amersham Monocyte Chemoattractant Protein-1 [(r)MCP-1]、Rat、Biotrak ELISA System、GE Healthcare、UK)により製造業者の指示に従って、SpectraVmax ELISA リーダー (Molecular Devices、UK)にて検出した。
試験対象物上の金属量は以下の通りであった; Ag: 0.8-0.9 μg/cm2 およびPd: 0.1 μg/cm2。
Pdの量をディスク上で、インビボで変動させた。Agの量はすべてのサンプルについて約 1 μg/cm2 であった(PMN = 多形核)。
本明細書の開示内容は、以下の態様を含み得る。
(態様1)
電子供与表面を有する生体適合性基体であって、前記表面上に金属粒子が存在することを特徴とし、前記金属粒子が、パラジウム、および、金、ルテニウム、ロジウム、オスミウム、イリジウム、および白金からなる群から選択される少なくとも1つの金属を含み、前記金属粒子の量が約0.001〜約8μg/cm 2 である基体。
(態様2)
前記電子供与表面が、約0.05〜約12μg/cm 2 の量にて適用された電子供与材料の層である態様1に記載の基体。
(態様3)
前記電子供与層が、パラジウム、金、ルテニウム、ロジウム、オスミウム、イリジウム、および白金からなる群における金属のいずれよりも卑な金属である態様2に記載の基体。
(態様4)
前記電子供与層が、銀、銅および亜鉛からなる群から選択される金属である態様3に記載の基体。
(態様5)
前記基体がポリマー性基体である態様1〜4のいずれか1項に記載の基体。
(態様6)
前記ポリマー性基体が、ラテックス、ビニル、ビニル基を含むポリマー、ポリウレタンウレア、シリコーン、ポリ塩化ビニル、ポリプロピレン、スチレン、ポリウレタン、ポリエステル、エチレン酢酸ビニルのコポリメリゼート、ポリスチレン、ポリカーボネート、ポリエチレン、ポリアクリレート、ポリメタクリレート、アクリロニトリルブタジエンスチレン、ポリアミド、およびポリイミド、またはそれらの混合物からなる群から選択される態様5に記載の基体。
(態様7)
前記ポリマー性基体が、天然ポリマー、分解可能ポリマー、食用ポリマー、生分解性ポリマー、環境に優しいポリマー、および医療グレードポリマーからなる群から選択される態様5に記載の基体。
(態様8)
前記基体が金属である態様1〜4いずれか1項に記載の基体。
(態様9)
前記金属が、ステンレス綱、医療グレード鋼、チタン、医療グレードチタン、コバルト、およびクロムまたはそれらの混合物からなる群から選択される態様8に記載の基体。
(態様10)
前記基体が、ガラス、無機質、ゼオライト、石およびセラミクスからなる群から選択される態様1〜4のいずれか1項に記載の基体。
(態様11)
前記基体が、紙、木、織り繊維、繊維、セルロース繊維、革、炭素、炭素繊維、グラファイト、ポリテトラフルオロエチレン、およびポリパラフェニレンテレフタルアミドからなる群から選択される態様1〜4のいずれか1項に記載の基体。
(態様12)
前記基体が粒子の形状を有する態様1〜11のいずれか1項に記載の基体。
(態様13)
金属粒子の量が約0.01〜約4μg/cm 2 である態様1〜12のいずれか1項に記載の基体。
(態様14)
前記金属粒子におけるパラジウムの非パラジウム金属に対する比が約0.01:99.99〜約99.99:0.01である態様1〜13のいずれか1項に記載の基体。
(態様15)
前記金属粒子におけるパラジウムの非パラジウム金属に対する比が約0.5:99.5〜約99.8:0.2である態様1〜13のいずれか1項に記載の基体。
(態様16)
前記金属粒子におけるパラジウムの非パラジウム金属に対する比が約2:98〜約95:5である態様1〜13のいずれか1項に記載の基体。
(態様17)
前記金属粒子がパラジウムに加えて金を含む態様1〜16のいずれか1項に記載の基体。
(態様18)
前記金属粒子の平均サイズが約10〜10000Åである態様1〜17のいずれか1項に記載の基体。
(態様19)
前記金属粒子の平均サイズが約100〜600Åである態様1〜18のいずれか1項に記載の基体。
(態様20)
態様1〜19のいずれか1項に記載の基体を含むことを特徴とする物。
(態様21)
医療機器であることを特徴とする態様20に記載の物。
(態様22)
使い捨て商品であることを特徴とする態様20に記載の物。
(態様23)
歯科用品であることを特徴とする態様20に記載の物。
(態様24)
表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm 2 である基体、または態様1〜19のいずれか1項に記載の基体の、前記基体を含む物に対するタンパク質吸着を改変するための使用。
(態様25)
表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm 2 である基体、または態様1〜19のいずれか1項に記載の基体の、前記基体を含む物に対する組織内殖を改変するための使用。
(態様26)
表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm 2 である基体、または態様1〜19のいずれか1項に記載の基体の、前記基体を含む物によって引き起こされる補体活性化を改変するための使用。
(態様27)
表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm 2 である基体、または態様1〜19のいずれか1項に記載の基体の、前記基体を含む物によって引き起こされる炎症反応を改変するための使用。
(態様28)
表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm 2 である基体、または態様1〜19のいずれか1項に記載の基体の、前記基体を含む物によって引き起こされる血液凝固を改変するための使用。
(態様29)
表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm 2 である基体、または態様1〜19のいずれか1項に記載の基体の、前記基体を含む物の摩擦係数を改変するための使用。
(態様30)
表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm 2 である基体、または態様1〜19のいずれか1項に記載の基体の、前記基体を含む物の表面の硬さを改変するための使用。
(態様31)
態様1〜19のいずれか1項に記載の基体を製造する方法であって、
a. 前記基体上への懸濁液からの金属粒子の析出工程、
b. 前記基体のすすぎ工程、および、
c. 前記基体の乾燥工程を含む基体の製造方法。
(態様32)
金属粒子の析出の前に前記基体上に電子供与材料を析出させる工程をさらに含む態様31に記載の方法。
Claims (32)
- 電子供与表面を有する生体適合性基体であって、前記表面上に金属粒子が存在することを特徴とし、前記金属粒子が、パラジウム、および、金、ルテニウム、ロジウム、オスミウム、イリジウム、および白金からなる群から選択される少なくとも1つの金属を含み、前記金属粒子の量が約0.001〜約8μg/cm2である基体。
- 前記電子供与表面が、約0.05〜約12μg/cm2の量にて適用された電子供与材料の層である請求項1に記載の基体。
- 前記電子供与層が、パラジウム、金、ルテニウム、ロジウム、オスミウム、イリジウム、および白金からなる群における金属のいずれよりも卑な金属である請求項2に記載の基体。
- 前記電子供与層が、銀、銅および亜鉛からなる群から選択される金属である請求項3に記載の基体。
- 前記基体がポリマー性基体である請求項1〜4のいずれか1項に記載の基体。
- 前記ポリマー性基体が、ラテックス、ビニル、ビニル基を含むポリマー、ポリウレタンウレア、シリコーン、ポリ塩化ビニル、ポリプロピレン、スチレン、ポリウレタン、ポリエステル、エチレン酢酸ビニルのコポリメリゼート、ポリスチレン、ポリカーボネート、ポリエチレン、ポリアクリレート、ポリメタクリレート、アクリロニトリルブタジエンスチレン、ポリアミド、およびポリイミド、またはそれらの混合物からなる群から選択される請求項5に記載の基体。
- 前記ポリマー性基体が、天然ポリマー、分解可能ポリマー、食用ポリマー、生分解性ポリマー、環境に優しいポリマー、および医療グレードポリマーからなる群から選択される請求項5に記載の基体。
- 前記基体が金属である請求項1〜4いずれか1項に記載の基体。
- 前記金属が、ステンレス綱、医療グレード鋼、チタン、医療グレードチタン、コバルト、およびクロムまたはそれらの混合物からなる群から選択される請求項8に記載の基体。
- 前記基体が、ガラス、無機質、ゼオライト、石およびセラミクスからなる群から選択される請求項1〜4のいずれか1項に記載の基体。
- 前記基体が、紙、木、織り繊維、繊維、セルロース繊維、革、炭素、炭素繊維、グラファイト、ポリテトラフルオロエチレン、およびポリパラフェニレンテレフタルアミドからなる群から選択される請求項1〜4のいずれか1項に記載の基体。
- 前記基体が粒子の形状を有する請求項1〜11のいずれか1項に記載の基体。
- 金属粒子の量が約0.01〜約4μg/cm2である請求項1〜12のいずれか1項に記載の基体。
- 前記金属粒子におけるパラジウムの非パラジウム金属に対する比が約0.01:99.99〜約99.99:0.01である請求項1〜13のいずれか1項に記載の基体。
- 前記金属粒子におけるパラジウムの非パラジウム金属に対する比が約0.5:99.5〜約99.8:0.2である請求項1〜13のいずれか1項に記載の基体。
- 前記金属粒子におけるパラジウムの非パラジウム金属に対する比が約2:98〜約95:5である請求項1〜13のいずれか1項に記載の基体。
- 前記金属粒子がパラジウムに加えて金を含む請求項1〜16のいずれか1項に記載の基体。
- 前記金属粒子の平均サイズが約10〜10000Åである請求項1〜17のいずれか1項に記載の基体。
- 前記金属粒子の平均サイズが約100〜600Åである請求項1〜18のいずれか1項に記載の基体。
- 請求項1〜19のいずれか1項に記載の基体を含むことを特徴とする物。
- 医療機器であることを特徴とする請求項20に記載の物。
- 使い捨て商品であることを特徴とする請求項20に記載の物。
- 歯科用品であることを特徴とする請求項20に記載の物。
- 表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm2である基体、または請求項1〜19のいずれか1項に記載の基体の、前記基体を含む物に対するタンパク質吸着を改変するための使用。
- 表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm2である基体、または請求項1〜19のいずれか1項に記載の基体の、前記基体を含む物に対する組織内殖を改変するための使用。
- 表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm2である基体、または請求項1〜19のいずれか1項に記載の基体の、前記基体を含む物によって引き起こされる補体活性化を改変するための使用。
- 表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm2である基体、または請求項1〜19のいずれか1項に記載の基体の、前記基体を含む物によって引き起こされる炎症反応を改変するための使用。
- 表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm2である基体、または請求項1〜19のいずれか1項に記載の基体の、前記基体を含む物によって引き起こされる血液凝固を改変するための使用。
- 表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm2である基体、または請求項1〜19のいずれか1項に記載の基体の、前記基体を含む物の摩擦係数を改変するための使用。
- 表面上に金属粒子を有する電子供与表面を有する基体であって、前記金属粒子がパラジウムを含み、前記金属粒子の量が約0.001〜約8μg/cm2である基体、または請求項1〜19のいずれか1項に記載の基体の、前記基体を含む物の表面の硬さを改変するための使用。
- 請求項1〜19のいずれか1項に記載の基体を製造する方法であって、
a. 前記基体上への懸濁液からの金属粒子の析出工程、
b. 前記基体のすすぎ工程、および、
c. 前記基体の乾燥工程を含む基体の製造方法。 - 金属粒子の析出の前に前記基体上に電子供与材料を析出させる工程をさらに含む請求項31に記載の方法。
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