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CN100415306C - 涂覆的牙齿植入物 - Google Patents

涂覆的牙齿植入物 Download PDF

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CN100415306C
CN100415306C CNB2004800080227A CN200480008022A CN100415306C CN 100415306 C CN100415306 C CN 100415306C CN B2004800080227 A CNB2004800080227 A CN B2004800080227A CN 200480008022 A CN200480008022 A CN 200480008022A CN 100415306 C CN100415306 C CN 100415306C
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dental implants
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alkoxyl
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R·登克
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    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08LCOMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L85/00Compositions of macromolecular compounds obtained by reactions forming a linkage in the main chain of the macromolecule containing atoms other than silicon, sulfur, nitrogen, oxygen and carbon; Compositions of derivatives of such polymers
    • C08L85/02Compositions of macromolecular compounds obtained by reactions forming a linkage in the main chain of the macromolecule containing atoms other than silicon, sulfur, nitrogen, oxygen and carbon; Compositions of derivatives of such polymers containing phosphorus
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012Means 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61CDENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012Means 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
    • A61C8/0013Means 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 with a surface layer, coating
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    • A61L27/28Materials for coating prostheses
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    • C08G79/00Macromolecular compounds obtained by reactions forming a linkage containing atoms other than silicon, sulfur, nitrogen, oxygen, and carbon with or without the latter elements in the main chain of the macromolecule
    • C08G79/02Macromolecular compounds obtained by reactions forming a linkage containing atoms other than silicon, sulfur, nitrogen, oxygen, and carbon with or without the latter elements in the main chain of the macromolecule a linkage containing phosphorus
    • C08G79/025Polyphosphazenes

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Abstract

本发明涉及涂覆的牙齿植入物,它可使齿龈充分接合到该牙齿植入物上,从而防止特别是龈沟的形成和齿龈的细菌感染;以及使用所述涂覆的牙齿植入物防止植入患者后龈沟形成和细菌感染的方法。

Description

涂覆的牙齿植入物
发明领域
本发明涉及涂覆的牙齿植入物,它可使齿龈充分接合到该牙齿植入物上,从而防止特别是龈沟的形成和齿龈的细菌感染;以及使用所述涂覆的牙齿植入物防止植入患者后龈沟形成和细菌感染的方法。
发明背景
已知人工植入物引起的最严重的并发症之一是患者体内植入物表面血小板的沉积增加。一种可能解决这种并发症的方法是使用涂覆的植入物。例如,DE19613 048描述了具有一种含抗血栓形成性化合物的生物相容性涂层的人工植入物。
人工牙齿植入物常常遇到的问题是齿龈和牙齿植入物之间的接合不充分;即,植入患体后牙齿植入物在齿龈上不充分的组织结合。不充分的接合往往导致龈沟的形成并增加细菌感染的危险。最坏的情况,还会导致严重的发炎并伴随牙齿植入物的脱落。
目前,现有技术中尚无可望解决齿龈充分接合到牙齿植入物上且没有或至少减少龈沟形成和/或没有或至少降低细菌感染危险的方案。
发明概述
本发明的一个目的是提供一种可使齿龈充分结合到牙齿植入物上的人工牙齿植入物,从而基本上防止植入患体后龈沟的形成,至少将细菌感染的危险降至最低,以及改善牙齿植入物的长期耐受性。
具体而言,本发明涉及一种包含具有生物相容性涂层的牙齿植入材料的牙齿植入物,所述涂层被涂在所述植入材料的至少一部分表面上,其中所述生物相容性涂层使得齿龈充分结合到牙齿植入物之上而得到以下结果(i)基本无龈沟形成,(ii)涂覆的牙齿植入物附近的齿龈基本没有细菌感染和(iii)涂覆的牙齿植入物具有改进的长期耐受性。
“至少部分表面”这个表述意指植入后应当与患者齿龈接触起来的那部分植入材料表面。
本发明的另一个目的是提供如下方法:将本发明的牙齿植入物植入患者体内后,(i)防止牙齿植入物处龈沟的形成,(ii)防止牙齿植入物处齿龈的细菌感染和(iii)使齿龈结合到牙齿植入物之上。
发明详述
在本发明的一个优选实施方案中,牙齿植入物包含一种具有生物相容性涂层的植入材料,所述涂层被涂在所述植入材料的至少一部分表面上,其中所述生物相容性涂层包含一种具有通式(I)的聚合物
其中
n为从2至∞
R1至R6是相同或不同的,并且表示烷氧基、烷磺酰基、二烷氨基或芳氧基,或具有氮作为杂原子的杂环烷基或杂芳基。
在通式(I)的聚合物中,优选基团R1和R2中至少一个为被至少一个氟原子取代的烷氧基。
在通式(I)的聚合物中,所述烷氧基、烷磺酰基和二烷氨基中的烷基是,例如,具有1至20个碳原子的直链或支链烷基,其中烷基可以被例如至少一个卤素原子如氟原子取代。
烷氧基的实例有甲氧基、乙氧基、丙氧基和丁氧基,其优选可被至少一个氟原子取代。特别优选的是2,2,2-三氟乙氧基。
烷磺酰基的实例有甲磺酰基、乙磺酰基、丙磺酰基和丁磺酰基。
二烷氨基的实例有二甲氨基、二乙氨基、二丙氨基和二丁氨基。
所述芳氧基中的芳基为,例如,具有一个或多个芳环体系的化合物,其中芳基可以被例如至少一个上文定义的烷基取代。
芳氧基的实例有苯氧基和萘氧基及其衍生物。
所述杂环烷基为例如一个环体系,它含有3至7个原子,至少一个环原子为氮原子。杂环烷基可以例如被至少一个上文定义的烷基取代。杂环烷基的实例有哌啶基、哌嗪基、吡咯烷基和吗啉基及其衍生物。
杂芳基为例如具有一个或多个芳环体系的化合物,其中至少一个环原子是氮原子。该杂芳基可以例如被至少一个上文定义的烷基取代。杂芳基的实例有吡咯基、吡啶基、吡啶醇基(pyridinolyl)、异喹啉基和喹啉基及其衍生物。
在本发明的一个优选实施方案中,生物相容性涂层含有聚合物双-聚-三氟乙氧基-聚磷腈。
从六氯环三磷腈开始制备通式(I)的聚合物如双-聚-三氟乙氧基-聚磷腈的方法是本领域已知的。六氯环三磷腈的聚合详细记载在Korsak et al.,Acta Polymerica 30,No.5,pages 245-246(1979)中。通过聚合制备的聚二氯磷腈的酯化记载在Fear,Thower and Veitch,J.Chem.Soc.,page 1324(1958)中。
本发明的牙齿植入物的生物相容性涂层具有,例如,约1nm至约100μm的厚度,优选约10mm至约10μm,更优选至多约1μm。
对用于未涂覆的牙齿植入物的材料没有特别限制。它可以是任何适用于牙齿植入物的植入材料。具体而言,牙齿植入材料可以是金属、合金、聚合材料或陶瓷材料。例如,金属材料可以是钛。在本发明的一个优选实施方案中,钛被电抛光从而获得未涂覆的牙齿植入物的TiO2表面。
在本发明的一个实施方案中,在未涂覆的牙齿植入物表面与生物相容性涂层之间提供一个含增粘剂的层。所述增粘剂或垫层是,例如一种有机硅化合物,优选为氨基封端的硅烷或基于氨基硅烷的化合物,或一种烷基膦酸。特别优选的是氨丙基三甲氧基硅烷。
通过利用例如离子和/或共价键把增粘剂偶联到牙齿植入材料表面,以及通过利用例如离子和/或共价键把增粘剂进一步偶联到反应组分特别是生物相容性涂层的聚合物上,增粘剂尤其改善了生物相容性涂层与牙齿植入材料表面的粘合效果。
齿龈与本发明牙齿植入物的惊人改进的接合可能基于,但不限于如下机理:本发明的牙齿植入物的生物相容性涂层吸附可逆天然蛋白质而不使其变性,从而模仿生物和生理学表面。本发明的牙齿植入物的这种独特性质可以改善和促进齿龈接合到牙齿植入物上而无龈沟形成。此外,可以防止本发明的牙齿植入物植入患者后该植入物处齿龈的细菌感染,而且可以改善本发明牙齿植入物的长期耐受性。
将在下述实施例中进一步阐述本发明,但本发明不限于这些实施例。
实施例1
细胞测试:
对涂覆的和未涂覆的钛片进行生物相容性测试。
采用HEKn-Keratinozytes对接种密度为30000个细胞/cm2的不同的涂覆的和未涂覆的钛片进行测试。在培养箱中使用EpiLife-培养基于37℃、5%CO2气氛下进行细胞培养。通过采用Brom-desoxy-Uridin标记试验期(trialphase)中的新生细胞以及比较620nm下Elisa-Reader中经过抗体反应产生的颜色的强度,测量新生细胞的增殖。
结果:
24小时后,与裸钛上的情况相比,用Polyzene-F涂覆的钛片显示明显更多的新生细胞。Ti=100%对比Ti-Polyzene-F=150.%。
实施例2
对由纯钛制成的15个传统的牙齿植入物(市售,来自Dr.Ihde Dental GmbH,Munich,STI,尺寸4.1mm直径,长度分别为11和13mm)进行电抛光(市售,来自Admedes Schüβler GmbH,Pforzheim)。此步骤提供了纯TiO2表面。将分子量高于1200万、氯浓度低于0.0005%的高纯线性Polyzene-F(双-聚-三氟乙氧基-聚磷腈,市售,来自Polyzenix GmbH,Ulm)应用于牙齿植入物的全部表面。将15个没有任何涂层的牙齿植入物用作对照物。将每个牙齿植入物都植入患者的颌骨并对齿龈在牙齿植入物上的组织结合进行评估。
植入大约八周以后,本发明的牙齿植入物显示齿龈与牙齿植入物完全接合且没有观察到龈沟。与之相反,对照组的牙齿植入物显示齿龈未与牙齿植入物充分接合,并在所述患者中观察到明显形成2mm或更深的龈沟,有些还伴有细菌感染。
本发明的牙齿植入物强有力地改善了植入患体后齿龈在牙齿植入物上的接合。这一惊人结果防止龈沟的形成,因而如果不能防止,也能把细菌感染的危险性降至最低。因此,齿龈在本发明的牙齿植入物上的充分接合充分地减少或防止了所述牙齿植入物的脱落,并且改善了所述牙齿植入物的长期耐受性。

Claims (6)

1. 生物相容性涂层在制造能防止牙齿植入物植入患者后在牙齿植入物处形成龈沟的牙齿植入物中的应用,其中将所述生物相容性涂层涂在植入材料的至少一部分表面上,其中所述生物相容性涂层包含一种具有通式(I)的聚合物
Figure C2004800080220002C1
其中
n为从2至∞
R1至R6是相同或不同的,并且表示烷氧基、烷磺酰基、二烷氨基或芳氧基,或具有氮作为杂原子的杂环烷基或杂芳基。
2. 根据权利要求1所述的用途,其中基团R1和R2中至少一个是被至少一个氟基取代的烷氧基。
3. 根据权利要求1所述的用途,其中生物相容性涂层包含一种双-聚-三氟乙氧基-聚磷腈。
4. 生物相容性涂层在制造植入患者后可将齿龈充分接合到牙齿植入物上的牙齿植入物中的应用,其中将所述生物相容性涂层涂在植入材料的至少一部分表面上,其中所述生物相容性涂层包含一种具有通式(I)的聚合物
Figure C2004800080220002C2
其中
n为从2至∞
R1至R6是相同或不同的,并且表示烷氧基、烷磺酰基、二烷氨基或芳氧基,或具有氮作为杂原子的杂环烷基或杂芳基。
5. 根据权利要求4所述的用途,其中基团R1和R2中至少一个是被至少一个氟基取代的烷氧基。
6. 根据权利要求4所述的用途,其中生物相容性涂层包含一种双-聚-三氟乙氧基-聚磷腈。
CNB2004800080227A 2003-03-26 2004-03-26 涂覆的牙齿植入物 Expired - Fee Related CN100415306C (zh)

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CN100415306C (zh) * 2003-03-26 2008-09-03 宝利策尼克斯有限公司 涂覆的牙齿植入物
US20210299056A9 (en) 2004-10-25 2021-09-30 Varian Medical Systems, Inc. Color-Coded Polymeric Particles of Predetermined Size for Therapeutic and/or Diagnostic Applications and Related Methods
JP2008536978A (ja) * 2005-04-15 2008-09-11 パラレル ソリューションズ,インク. ピロリドン側基を含む生分解性ポリホスファゼン
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FR2985908B1 (fr) 2012-01-24 2014-02-07 Univ Claude Bernard Lyon Substrat sur lequel est greffe par liaison covalente du chitosane ou du collagene
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US20060068363A1 (en) 2006-03-30
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JP2011093911A (ja) 2011-05-12
EP1605983B1 (en) 2011-01-05
DE602004030892D1 (de) 2011-02-17
CA2519811A1 (en) 2004-10-07
EP1605983A1 (en) 2005-12-21
ES2355727T3 (es) 2011-03-30
BRPI0408775A (pt) 2006-03-28
WO2004084966A1 (en) 2004-10-07
US20070122768A1 (en) 2007-05-31
CA2519811C (en) 2012-07-10
AU2004224772B2 (en) 2009-09-10
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