JP2009172365A - 骨内インプラント - Google Patents
骨内インプラント Download PDFInfo
- Publication number
- JP2009172365A JP2009172365A JP2008311703A JP2008311703A JP2009172365A JP 2009172365 A JP2009172365 A JP 2009172365A JP 2008311703 A JP2008311703 A JP 2008311703A JP 2008311703 A JP2008311703 A JP 2008311703A JP 2009172365 A JP2009172365 A JP 2009172365A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- implant
- bmp
- salt
- formula
- 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.)
- Granted
Links
- 239000007943 implant Substances 0.000 title claims abstract description 97
- 150000002148 esters Chemical class 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 29
- 239000002184 metal Substances 0.000 claims abstract description 25
- 229910052751 metal Inorganic materials 0.000 claims abstract description 24
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 16
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000919 ceramic Substances 0.000 claims abstract description 12
- 150000002894 organic compounds Chemical class 0.000 claims abstract description 10
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052726 zirconium Inorganic materials 0.000 claims abstract description 9
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical group [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910045601 alloy Inorganic materials 0.000 claims abstract description 8
- 239000000956 alloy Substances 0.000 claims abstract description 8
- 229910052782 aluminium Inorganic materials 0.000 claims abstract description 8
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052804 chromium Inorganic materials 0.000 claims abstract description 8
- 239000011651 chromium Substances 0.000 claims abstract description 8
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- 229910017052 cobalt Inorganic materials 0.000 claims abstract description 8
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims abstract description 8
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- 229910052759 nickel Inorganic materials 0.000 claims abstract description 8
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- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 claims abstract description 8
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- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 10
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- 239000010936 titanium Substances 0.000 claims description 8
- 229910052719 titanium Inorganic materials 0.000 claims description 8
- SOOWMZPJQNFUQH-UHFFFAOYSA-N 2,5-diphosphonopentan-2-ylphosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(C)CCCP(O)(O)=O SOOWMZPJQNFUQH-UHFFFAOYSA-N 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 229920001184 polypeptide Polymers 0.000 claims description 7
- 239000010935 stainless steel Substances 0.000 claims description 7
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 claims description 7
- LKDJBKDTLDKCIG-UHFFFAOYSA-N 1,4,7-triphosphonoheptan-4-ylphosphonic acid Chemical compound OP(O)(=O)CCCC(P(O)(O)=O)(P(O)(O)=O)CCCP(O)(O)=O LKDJBKDTLDKCIG-UHFFFAOYSA-N 0.000 claims description 6
- KEXHFABLRBJINQ-UHFFFAOYSA-N 1,5-diphosphonopentylphosphonic acid Chemical compound OP(O)(=O)CCCCC(P(O)(O)=O)P(O)(O)=O KEXHFABLRBJINQ-UHFFFAOYSA-N 0.000 claims description 6
- SDOPALDWANYZLE-UHFFFAOYSA-N 2,6-diphosphonohexan-2-ylphosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(C)CCCCP(O)(O)=O SDOPALDWANYZLE-UHFFFAOYSA-N 0.000 claims description 6
- 102100022545 Bone morphogenetic protein 8B Human genes 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 6
- 235000001014 amino acid Nutrition 0.000 claims description 6
- 125000000539 amino acid group Chemical group 0.000 claims description 6
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 6
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 6
- YNVHCYRLEXBBCI-UHFFFAOYSA-N 1,4-diphosphonobutylphosphonic acid Chemical compound OP(O)(=O)CCCC(P(O)(O)=O)P(O)(O)=O YNVHCYRLEXBBCI-UHFFFAOYSA-N 0.000 claims description 5
- OVFUHIUVETVJHU-UHFFFAOYSA-N 1,5,9-triphosphonononan-5-ylphosphonic acid Chemical compound OP(O)(=O)CCCCC(P(O)(O)=O)(P(O)(O)=O)CCCCP(O)(O)=O OVFUHIUVETVJHU-UHFFFAOYSA-N 0.000 claims description 5
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 claims description 5
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- NRTOMJZYCJJWKI-UHFFFAOYSA-N Titanium nitride Chemical compound [Ti]#N NRTOMJZYCJJWKI-UHFFFAOYSA-N 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229930195734 saturated hydrocarbon Chemical group 0.000 claims description 5
- SFRLSTJPMFGBDP-UHFFFAOYSA-N 1,2-diphosphonoethylphosphonic acid Chemical compound OP(O)(=O)CC(P(O)(O)=O)P(O)(O)=O SFRLSTJPMFGBDP-UHFFFAOYSA-N 0.000 claims description 4
- MVGVETXJIBEYSY-UHFFFAOYSA-N 1,5,5-triphosphonopentylphosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)CCCC(P(O)(O)=O)P(O)(O)=O MVGVETXJIBEYSY-UHFFFAOYSA-N 0.000 claims description 4
- ODTQUKVFOLFLIQ-UHFFFAOYSA-N 2-[di(propan-2-yloxy)phosphorylmethyl-propan-2-yloxyphosphoryl]oxypropane Chemical compound CC(C)OP(=O)(OC(C)C)CP(=O)(OC(C)C)OC(C)C ODTQUKVFOLFLIQ-UHFFFAOYSA-N 0.000 claims description 4
- PUVMVPFLXCHEOY-UHFFFAOYSA-N 3-phosphonopropylphosphonic acid Chemical compound OP(O)(=O)CCCP(O)(O)=O PUVMVPFLXCHEOY-UHFFFAOYSA-N 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 150000002430 hydrocarbons Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical compound OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 claims description 4
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- 150000004767 nitrides Chemical class 0.000 claims description 4
- MTPVUVINMAGMJL-UHFFFAOYSA-N trimethyl(1,1,2,2,2-pentafluoroethyl)silane Chemical compound C[Si](C)(C)C(F)(F)C(F)(F)F MTPVUVINMAGMJL-UHFFFAOYSA-N 0.000 claims description 4
- MDNRBNZIOBQHHK-KWBADKCTSA-N (2s)-2-[[(2s)-2-[[2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-3-methylbutanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N MDNRBNZIOBQHHK-KWBADKCTSA-N 0.000 claims description 3
- LHFCYWXOMSLPEB-UHFFFAOYSA-N 1,1,4-tris[di(propan-2-yloxy)phosphoryl]butane Chemical compound CC(C)OP(=O)(OC(C)C)CCCC(P(=O)(OC(C)C)OC(C)C)P(=O)(OC(C)C)OC(C)C LHFCYWXOMSLPEB-UHFFFAOYSA-N 0.000 claims description 3
- YVPHSTVRTGSOSK-UHFFFAOYSA-N 1,3,3-triphosphonopropylphosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)CC(P(O)(O)=O)P(O)(O)=O YVPHSTVRTGSOSK-UHFFFAOYSA-N 0.000 claims description 3
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- 101000781681 Protobothrops flavoviridis Disintegrin triflavin Proteins 0.000 claims description 3
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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- A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
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- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- C07F9/3839—Polyphosphonic acids
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Abstract
【解決手段】選択された金属もしくは選択された金属合金またはセラミックで製造された表面を有し、前記金属、金属合金のそれぞれが、クロム、ニオブ、タンタル、バナジウム、ジルコニウム、アルミニウム、コバルト、ニッケル、ステンレス鋼、またはその合金から選択され、前記表面は滑らかなまたは粗いテキスチャーを有し、前記表面が、少なくとも1つのホスホン酸基、またはその誘導体であって、好ましくは薬学的に許容されるその塩またはエステルまたはアミド、を保有する少なくとも1つの薬学的に許容される有機化合物で処理されていることを特徴とするインプラント。
【選択図】なし
Description
A−[P(O)(OH)2]p (I)、
(式中、AはA1またはA2を意味し、
A1は、n個の炭素原子を有する直鎖状、分枝鎖状または環状の、飽和または不飽和の炭化水素残基の残基であり、該残基はヒドロキシルおよび/またはカルボキシルによって置換され、および場合により1つ以上の酸素原子および/またはイオウ原子および/または窒素原子によって中断されていてよく、p個のホスホン酸基を保有し、ここで
nは1〜70、好ましくは1〜40、好ましくは1〜22の数であり、
pは1、2、3、4、5、または6、好ましくは1、2、3、4、または5、好ましくは1、2、3、または4であるか;あるいは
AはA2を意味し、A2はアミノ酸の残基またはタンパク質もしくはポリペプチドのそれぞれのアミノ酸配列の残基、好ましくはトランスフォーミング成長因子ベータ(TGF−β)のスーパーファミリーの残基であり;または特定の薬物分子の残基であり、ここで
各残基A2がp個のホスホン酸基を保有し、
A2がアミノ酸の残基またはタンパク質もしくはポリペプチドのそれぞれのアミノ酸配列の残基であるとき、pは1〜6、好ましくは1、2、3、または4、好ましくは1、2、または3であり;または
A2は本来いかなるホスホン基も有さず、場合によりA1に対して示された定義に属する特定の薬物分子の残基であるとき、pは1、2、3、4、5、または6、好ましくは1、2、または3、好ましくは1である)、
または薬学的に許容されるその誘導体であって、好ましくは薬学的に許容されるそのエステル、アミドまたは塩、に対応する少なくとも1つの有機化合物、またはこの化合物の混合物で処理されている。
米国特許第3,400,176号明細書、B.A.Arbusov,Pure Appl.Chem.9(1967)、307〜353ページ、およびその中の引例に従って、メチレンジホスホン酸を合成した。NMR(1H、31P、13C)、質量分光法による元素分析、およびその融点によって化合物を同定した。これらのデータすべては、O.T.Quimbyらの文献、Metalated methylendiphosphonate esters, preparation, characterization and synthesis applications、J.of Organomet.Chem.13、199〜207(1968)と一致した。
A)直径4mm、長さ10mmを有するスクリューの形状のチタン製の歯科用インプラントを従来の方法で製造した。体内に植え込まれる表面には、EP0 388 575に従って、平均粒径0.25〜0.5mmを用いて表面をサンドブラストした後、比が2:1:1の塩酸/硫酸/水の混合物を含有する水性酸性混合物の混合物で約80℃の温度下、約5分間処理することによって、0.15MのNaClによる水性電解液中でボルタメトリ法で測定すると、研磨表面に比べて約3.6倍粗いインプラントの表面が得られた。次いで、インプラントの表面を窒素プラズマで化学処理し、B.−O.Aronssonら、J.Biomed.Mater.Res.35(1997)、49ページ以降に記載されたチタン窒化物表面を得た。処理したインプラントのそれぞれの表面を15分間、30℃下に2回蒸留水中で超音波処理し、純水で洗浄した後、水中で(3回)10分間、超音波処理し、次いで純へキサンですすぎ洗いをし、真空(10mmHg、室温)下で乾燥させた。
インプラントの最初のチタン表面がアルゴングロー放電プラズマ中のメタンで処理して、チタン炭化物の表面を得た点を除いて、実施例2を繰り返した。処理は、B.O.Aronssonら、J.Biomed.Mater.Res.35(1997)、49ページ以降に記載されたとおりに行った。表1に示したものと類似の試験結果が得られた。
インプラントがジルコニウムで製造され、ジルコニウム酸化物表面を有するとともに、式(I)に記載の化合物が、グリシン分子のアミン末端をホスホン酸塩基の1つに結合することによって改変されているエタン−1,1,3−トリホスホン酸である点を除いて、実施例2を繰り返した。表1に示した類似の試験結果が得られた。
式(I)に記載の化合物が、GRGDS細胞結合ポリペプチドのアミン末端をホスホン酸塩基の1つに結合することによって改変されているエタン−1,1,3−トリホスホン酸である点を除いて、実施例2および3を繰り返した。表1に示した類似の試験結果が得られた。
式(I)に記載の化合物が、ヒト骨形態形成タンパク質2型(BMP−2)のアミン末端(メチオニン)をホスホン酸塩基の1つに結合することによって改変されているエタン−1,1,3−トリホスホン酸である点を除いて、実施例2および3を繰り返し、表1に示したのと類似の試験結果を得た。
Claims (26)
- ヒトまたは動物の骨に適用される骨内インプラントであって、前記インプラントは、選択された金属もしくは選択された金属合金またはセラミックで製造された表面を有し、前記金属、金属合金のそれぞれが、クロム、ニオブ、タンタル、バナジウム、ジルコニウム、アルミニウム、コバルト、ニッケル、ステンレス鋼、またはその合金から選択され、前記表面は滑らかなまたは粗いテキスチャーを有し、
前記表面が、少なくとも1つのホスホン酸基、またはその誘導体であって、好ましくは薬学的に許容されるそのエステル、アミドまたは塩、を保有する少なくとも1つの薬学的に許容される有機化合物で処理されていることを特徴とするインプラント。 - インプラントの表面が、クロム、ニオブ、タンタル、バナジウム、ジルコニウム、アルミニウム、コバルト、ニッケル、ステンレス鋼、またはその合金の酸化物表面、炭化物表面、窒化物表面、酸窒化物表面、炭窒化物表面、または酸炭化物表面から選択されるセラミックで製造されることを特徴とする、請求項1に記載のインプラント。
- インプラントの表面が、チタン炭化物、チタン窒化物、チタン酸窒化物、チタン炭窒化物および/またはチタン酸炭化物で製造されることを特徴とする、請求項1に記載のインプラント。
- インプラントの表面が、金属酸化物、好ましくはアルミニウム酸化物またはジルコニウム酸化物またはケイ素酸化物で製造され、好ましくはアパタイト類、好ましくはヒドロキシアパタイトまたはフルオロアパタイト、またはアパタイト状材料、好ましくはトリカルシウムリン酸塩、またはブラッシュ石型層で製造されることを特徴とする、請求項1に記載のインプラント。
- インプラントの表面が、ガラス状材料、好ましくはケイ酸ガラスまたはホウ素シリカガラスまたはバイオガラスで製造されることを特徴とする、請求項1に記載のインプラント。
- インプラントの表面が、一般式(I):
A−[P(O)(OH)2]p (I)
(式中、AはA1またはA2を意味し、
A1は、n個の炭素原子を有する直鎖状、分枝鎖状または環状の、飽和または不飽和の炭化水素残基の残基であり、前記残基はヒドロキシルおよび/またはカルボキシルによって置換され、および場合により1つ以上の酸素原子および/またはイオウ原子および/または窒素原子によってさらに中断されていてもよく、p個のホスホン酸基を保有し、ここで
nは1〜70、好ましくは1〜40、好ましくは1〜22の数であり、
pは1、2、3、4、5、または6、好ましくは1、2、3、4、または5、好ましくは1、2、3、または4であるか;あるいは
AはA2を意味し、
A2は、アミノ酸の残基またはタンパク質もしくはポリペプチドのそれぞれのアミノ酸配列の残基、好ましくはトランスフォーミング成長因子ベータ(TGF−β)のスーパーファミリーの残基であり;または特定の薬物分子の残基であり、ここで
各残基A2がp個のホスホン酸基を保有し、
A2がアミノ酸の残基またはタンパク質もしくはポリペプチドのそれぞれのアミノ酸配列の残基であるとき、pは1〜6、好ましくは1、2、3、または4、好ましくは1、2、または3であり;または
A2は本来いかなるホスホン基も有さず、場合によりA1に対して示された定義に属する特定の薬物分子の残基であるとき、pは1、2、3、4、5、または6、好ましくは1、2、または3、好ましくは1である)、
または薬学的に許容されるその誘導体であって、好ましくは薬学的に許容されるそのエステル、アミドまたは塩、に対応する少なくとも1つの有機化合物、またはこの化合物の混合物で処理されていることを特徴とする、請求項1〜5のいずれか一項に記載のインプラント。 - AがA1の意味を有する場合、nが1であり、pが2であるとき、Aは−CH2−であり;またはnが1であるとき、pは3または4、好ましくは3であり;またはnが2〜10であるとき、各ホスホン酸基またはその誘導体、好ましくはホスホン酸エステル基が同じ分子内の異なる炭素原子に結合されているという条件で、pは2であり;またはnが2〜10であるとき、pは3、4、5、または6、好ましくは3、4、または5、好ましくは3または4であり;またはnが11〜70であるとき、pは2、3、4、5、または6、好ましくは2、3、4、または5、好ましくは2、3、または4である、請求項6に記載のインプラント。
- AがA2の意味を有する場合、A2は本来いかなるホスホン基も有さず、場合によりA1に対して示された定義に属する特定の薬物分子の残基である場合には、pは1または3〜6、好ましくは1である、請求項6に記載のインプラント。
- A1が式−(CnH2n+2-p)−[式中、nは1〜70、好ましくは1〜40、好ましくは1〜22を意味する]の飽和炭化水素残基である、請求項1に記載のインプラント。
- 式(I)の化合物がアルカリ塩、好ましくはナトリウム塩またはカリウム塩であることを特徴とする、請求項1〜9のいずれか一項に記載のインプラント。
- 式(I)の化合物が、モノホスホン酸、好ましくはメタンホスホン酸、エタンホスホン酸、プロパンホスホン酸、またはポリホスホン酸、好ましくはメチレンジホスホン酸、エタン−1,2−ジホスホン酸、プロパン−1,3−ジホスホン酸、プロパン−1,3−ジホスホン酸、エタン−1,1,2−トリホスホン酸、ブタン−1,1,4−トリホスホン酸、ペンタン−1,1,5−トリホスホン酸、ペンタン−2,2,5−トリホスホン酸、ヘキサン−2,2,6−トリホスホン酸、ペンタン−1,1,5,5−テトラホスホン酸、ヘプタン−1,4,4,7−テトラホスホン酸、プロパン−1,1,3,3−テトラホスホン酸、またはノナン−1,5,5,9−テトラホスホン酸から、または不飽和モノホスホン酸およびポリホスホン酸から選択されることを特徴とする、請求項1〜10のいずれか一項に記載のインプラント。
- 薬学的に許容されるエステルが、ホスホン酸イソプロピルまたはホスホン酸エチルエステルであることを特徴とする、請求項1〜11のいずれか一項に記載のインプラント。
- エステルが、メチレンジホスホン酸テトライソプロピル、エタン−1,1,2−トリホスホン酸ヘキサエチル、ブタン−1,1,4−トリホスホン酸ヘキサイソプロピル、ペンタン−1,1,5−トリホスホン酸ヘキサイソプロピル、ペンタン−2,2,5−トリホスホン酸ヘキサイソプロピル、ヘキサン−2,2,6−トリホスホン酸ヘキサイソプロピル、プロパン−1,1,3,3−テトラホスホン酸オクタイソプロピル、ヘプタン−1,4,4,7−テトラホスホン酸オクタイソプロピル、ノナン−1,5,5,9−テトラホスホン酸オクタイソプロピルの群から選択されることを特徴とする、請求項12に記載のインプラント。
- 式(I)の化合物が、成長因子のスーパーファミリーのメンバーによって規定されたトランスフォーミング成長因子ベータ(TGF−β)、好ましくはTGF−β1、TGF−β2、TGF−β3、TGF−β4、およびTGF−β5を表し、ここでつねにぺプチド鎖が少なくとも1つのアルキルホスホン酸基、またはその誘導体であって、好ましくはそのエステル、アミドまたは塩、を含むように改変されている、請求項1に記載のインプラント。
- 式(I)の化合物が、骨形態形成タンパク質(BMP)、好ましくはBMP−2(BMP−2a)、BMP−3、BMP−4(BMP−2b)、BMP−5、BMP−6、BMP−7(OP−1)、BMP−8(OP−2)、BMP−9、BMP−10、BMP−11、BMP−12、BMP−13を表し、ここでペプチド鎖が少なくとも1つのアルキルホスホン酸基、またはその誘導体であって、好ましくはそのエステル、アミドまたは塩、を含むように改変されている、請求項1に記載のインプラント。
- 式(I)の化合物、が2−アミノ−4,4−ビス−(ジエトキシ−ホスホリル)−酪酸、2−アミノ−5−(ジエトキシ−ホスホリル)−ペンタン酸、および/または2−アミノ−4−ホスホノ酪酸から選択される、請求項1に記載のインプラント。
- 式(I)の化合物が、主要な20種のアミノ酸、好ましくはアルギニン、グリシン、アスパラギン酸、アラニン、バリン、プロリン、セリン、スレオニン、システイン、またはリジンの1つから選択され、そのアミノ酸が少なくとも1つのアルキルホスホン酸基、またはその誘導体であって、好ましくはそのエステル、アミドまたは塩、を含むように改変されている、請求項1に記載のインプラント。
- 式(I)の化合物が、RGD含有ペプチド、好ましくは、少なくとも1つのアルキルホスホン酸基、またはその誘導体であって、好ましくはそのエステル、アミドまたは塩、を含むように改変されているRGDSペプチド、GRGDSペプチド、RGDVペプチド、RGDEペプチド、および/またはRGDTペプチドである、請求項1に記載のインプラント。
- 式(I)の化合物が、1−ヒドロキシ−3−(1−ピロリジニル)−プロピリデンジホスホン酸、シクロヘプチルアミノメチレンジホスホン酸、1−ヒドロキシ−2−イミダゾ−(1,2−a)−ピリジン−3−イル−エチリデンジホスホン酸、1−ヒドロキシ−2−(3−ピリジニル)−エチリデンジホスホン酸、(4−クロロフェニル)チオ−メチレンジホスホン酸、1−ヒドロキシ−2−(1H−イミダゾール−1−イル)エチリデンジホスホン酸、および関連する化合物から選択される、請求項1に記載のインプラント。
- 前記表面が、薬学的に許容される少なくとも1つの式(I)の有機化合物またはその塩もしくはエステルもしくはアミドで処理されることを特徴とする、請求項1〜19のいずれか一項に記載のインプラントを製造するための方法。
- スクリュー、プレート、釘、ピン、および特別に形成された部品の形状における請求項1〜20のいずれか一項に記載のインプラントであって、医療、より具体的には、整形外科において損傷または疾患のある骨を置換または強化するために、および歯科において義歯を固定するために、または骨固定された補聴器をヒトまたは動物の骨格構造に固定するために、補綴物として用いることができるインプラント。
- 前記インプラントが、プラスチックまたは金属のパッケージング材料、好ましくは場合により排気され、または不活性気体もしくは不活性液体で充填された気密パッケージングで包装されていることを特徴とする、請求項21に記載のインプラント。
- 前記パッケージングが、無機塩および/または式(I)の化合物またはその塩もしくはエステルを、好ましくは水の約1.0×10-5mol/10ml〜5×10-2mol/10ml、好ましくは約5×10-4mol/10ml〜2.0×10-2mol/10mlの濃度で含有する純水で充填されていることを特徴とする、請求項22に記載のインプラント。
- pが3〜6、好ましくは3または4であり、nが4〜70、好ましくは4〜40、好ましくは4〜22である、請求項1〜19のいずれか1つの請求項に記載の式(I)に記載の化合物、その塩またはエステル。
- ブタン−1,1,4−トリホスホン酸、ペンタン−1,1,5−トリホスホン酸、ペンタン−2,2,5−トリホスホン酸、ヘキサン−2,2,6−トリホスホン酸、ペンタン−1,1,5,5−テトラホスホン酸、ヘプタン−1,4,4,7−テトラホスホン酸、またはノナン−1,5,5,9−テトラホスホン酸、その塩またはエステルまたはアミドである、請求項24に記載の化合物。
- 対応するエステルを酸の存在下で加水分解することを特徴とする、請求項24および25に記載のそれらの酸の形態の化学化合物を製造するための方法。
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PCT/EP2000/011510 WO2002040073A1 (en) | 2000-11-20 | 2000-11-20 | Endosseous implant |
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2001
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Patent Citations (4)
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US3400176A (en) * | 1965-11-15 | 1968-09-03 | Procter & Gamble | Propanepolyphosphonate compounds |
GB1254466A (en) * | 1967-12-11 | 1971-11-24 | Procter & Gamble | Pharmaceutical methods and compositions |
JPH0673573A (ja) * | 1991-11-23 | 1994-03-15 | Fmc Corp Uk Ltd | 腐食及び/又はスケール防止組成物 |
JPH08508661A (ja) * | 1993-04-14 | 1996-09-17 | レイラス オサケユイチア | 骨内材料を処理する方法 |
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