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1. 发明授权

US07276482B2 Peptide and peptide mimetic derivatives with integrin-inhibitors properties II 有权
标题翻译：具有整合蛋白抑制剂性质的肽和肽模拟衍生物II
公开(公告)号：US07276482B2
公开(公告)日：2007-10-02
申请号：US10344668
申请日：2001-08-02
申请人： Joerg Meyer , Berthold Nies , Michel Dard , Guenter Hoelzemann , Horst Kessler , Martin Kantlehner , Ulrich Hersel , Christoph Gibson , Gabor Sulyok
发明人： Joerg Meyer , Berthold Nies , Michel Dard , Guenter Hoelzemann , Horst Kessler , Martin Kantlehner , Ulrich Hersel , Christoph Gibson , Gabor Sulyok
IPC分类号： A61K38/10
CPC分类号： C07K7/06 , A61K38/00 , C07K14/78 , Y02P20/125
摘要： The invention relates to compounds of formula (I) B-Q-X1, wherein B is a bioactive, cell adhesive mediating molecule, selected from the group (i) and Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (SEQ ID NO: 1) (ii), Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (SEQ ID NO: 2) (iii), Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (SEQ ID NO: 3) (iv), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg (SEQ ID NO: 4) (v), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn (SEQ ID NO: 5) (vi), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg (SEQ ID NO: 6) (vii), wherein (i) X, Y, Z, R2, R3, R4, A, Ar, Hal, Het, Het1, n, m, o, p, q, s, t have the meanings cited in claim 1, Q is absent or is an organic spacer molecule, X1 is an anchor molecule selected from the group cited in claim 1, and the salts thereof, which can be used as integrin inhibitors particularly for treatment of illness, deficiencies and inflammations caused by implants and osteolytic illnesses such as osteoporosis, thrombosis, cardiac infarction and arteriosclerosis, in addition to the acceleration and strengthening of the integration process of implants or the biocompatible surface in tissue.
摘要翻译：本发明涉及式（I）BQX 1的化合物，其中B是选自（i）和Thr-Trp-Tyr-Lys-Ile-Ala的生物活性的细胞粘附介导分子 -Ph-Gln-Arg-Asn-Arg-Lys（SEQ ID NO：1）（ii），Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys（SEQ ID NO：）（iii），Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys（SEQ ID NO：3）（iv），Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln -Arg-Asn-Arg（SEQ ID NO：4）（v），Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn（SEQ ID NO：5）（vi） -Tyr-Lys-Ile-Ala-Phe-Gln-Arg（SEQ ID NO：6）（vii），其中（i）X，Y，Z，R 2，R 3 A，Ar，Hal，Het，Het 1，n，m，o，p，q，s，t具有引用的含义在权利要求1中，Q不存在或是有机间隔分子，X 1是选自权利要求1所述的基团的锚定分子及其盐，其可以用作整联蛋白抑制剂，特别是用于治疗由植入物和溶骨性疾病引起的疾病，缺陷和炎症例如骨质疏松症，血栓形成，心肌梗死和动脉硬化，以及植入物或组织中生物相容性表面的整合过程的加速和加强。

2. 发明授权

US07655624B2 Peptide and peptide mimetic conjugates with integrin-inhibitor properties 有权
标题翻译：具有整合素抑制剂性质的肽和肽模拟物缀合物
公开(公告)号：US07655624B2
公开(公告)日：2010-02-02
申请号：US10344669
申请日：2001-08-02
申请人： Joerg Meyer , Berthold Nies , Michel Dard , Guenter Hoelzemann , Horst Kessler , Martin Kantlehner , Ulrich Hersel , Christoph Gibson , Gabor Sulyok
发明人： Joerg Meyer , Berthold Nies , Michel Dard , Guenter Hoelzemann , Horst Kessler , Martin Kantlehner , Ulrich Hersel , Christoph Gibson , Gabor Sulyok
IPC分类号： A61K38/12 , A61F2/02
CPC分类号： A61K47/6435 , A61K47/6425
摘要： The invention relates to compounds of formula (1) B-Q-X1, wherein B is bioactive cell adhesive mediating molecule. Q is absent or is an inorganic spacer molecule and X1 is an anchor molecule, selected from the group Lys-(CO—CH2—(CH2)n—PO3H2)2(I), -Lys-[-Lys-(CO—CH2—(CH2)a—PO3H2)2]2(ii) or -Lys-(Lys[-Lys-(CO—CH2—(CH2)n—PO3H2]2 (iii), and n independently represents 0, 1, 2 or 3, wherein a free amino group of group B is linked in peptide form to a free carboxyl group of the spacer molecule Q or of the anchor molecule X1, or a free amino group of the radical Q is linked in peptide form to a free carboxyl group of the radical X1. The invention also relates to the salts thereof. The inventive compounds can be used as integrin inhibitors for the treatment of illnesses, deficiencies, inflammations caused by implants and osteolytic illnesses such as osteoporosis, thrombosis, cardiac infarction and arteriosclerosis, in addition to the acceleration and strengthening of the integration process of implants or the biocompatible surface in tissue.
摘要翻译：本发明涉及式（1）B-Q-X1的化合物，其中B是生物活性细胞粘附介导分子。 Q不存在或是无机间隔分子，X1是选自Lys-（CO-CH 2 - （CH 2）n -PO 3 H 2）2（I），-Lys - [ - Lys-（CO-CH 2） - （CH 2）a-PO 3 H 2）2] 2（ⅱ）或-Lys-（Lys [-Lys-（CO-CH 2 - （CH 2）n -PO 3 H 2] 2（ⅲ），n独立地表示0,1,2 或3，其中B族的游离氨基以间隔分子Q或锚分子X1的游离羧基形式连接，或者基团Q的游离氨基以肽形式连接至游离氨基本发明还涉及其盐。本发明化合物可用作整联蛋白抑制剂，用于治疗由植入物引起的疾病，缺血性和溶骨性疾病如骨质疏松症，血栓形成，心肌梗塞和动脉硬化，除了加速和加强植入物或组织中生物相容性表面的整合过程。

3. 发明授权

US06280760B1 Peptide-coated implants and methods for producing same 有权
标题翻译：肽涂覆植入物及其制备方法
公开(公告)号：US06280760B1
公开(公告)日：2001-08-28
申请号：US09423347
申请日：1999-11-22
申请人： Jorg Meyer , Alfred Jonczyk , Berthold Nies , Horst Kessler , Dirk Finsinger , Martin Kantlehner
发明人： Jorg Meyer , Alfred Jonczyk , Berthold Nies , Horst Kessler , Dirk Finsinger , Martin Kantlehner
IPC分类号： A61L2700
CPC分类号： C12N5/0068 , A61K35/12 , A61L27/34 , C12N5/0654 , C12N2533/50 , C08L89/00
摘要： The invention describes the possibility of the biofunctionalization of biomaterials, in particular implants, by their made-to-measure coating with synthesized cell- or tissue-selective RGD peptides which in vitro stimulate the adhesion of mainly those cell species which in each case are intended to accomplish the tissue integration of the appropriate biomaterial.
摘要翻译：本发明描述了通过其合成的细胞或组织选择性RGD肽的生物材料（特别是植入物）的生物功能化生物功能化的可能性，所述细胞或组织选择性RGD肽体外刺激主要在每种情况下被预期的那些细胞种类的粘附完成适当生物材料的组织整合。

4. 发明申请

US20050261169A1 Peptide and peptide mimetic derivatives having integrin inhibitor properties III 审中-公开
标题翻译：具有整合素抑制剂性质的肽和肽模拟物衍生物III
公开(公告)号：US20050261169A1
公开(公告)日：2005-11-24
申请号：US10858480
申请日：2004-06-02
申请人： Anja Enderle , Berthold Nies , Horst Kessler , Jorg Auerheimer , Ulrich Hersel , Claudia Dahmen
发明人： Anja Enderle , Berthold Nies , Horst Kessler , Jorg Auerheimer , Ulrich Hersel , Claudia Dahmen
IPC分类号： A61K47/48 , A61K6/02 , A61K6/033 , A61K38/00 , A61K38/12 , A61L27/00 , A61L27/22 , A61P7/02 , A61P9/10 , A61P19/10 , A61P29/00 , A61P37/06 , C07K7/02 , C07K7/64 , C07K14/745 , A61K38/16
CPC分类号： C07K14/745 , A61K38/00 , C07K7/64 , Y02P20/125
摘要： Compounds of the formula I B-Q-X1 and processes for their preparation, wherein B, Q and X, are as defined in the application, and salts thereof as integrin inhibitors for the treatment of diseases, defects and inflammation caused by implants and of osteolytic diseases, such as osteoporosis, thrombosis, cardiac infarction and arteriosclerosis, and for the acceleration and strengthening of the integration process of the implant or of the biocompatible surface into the tissue.
摘要翻译：式I BQX 1的化合物及其制备方法，其中B，Q和X如本申请中所定义，及其盐作为用于治疗疾病，缺陷和炎症的整联蛋白抑制剂通过植入物和溶骨性疾病如骨质疏松症，血栓形成，心肌梗塞和动脉硬化以及用于加速和加强植入物或生物相容性表面进入组织的整合过程。

5. 发明授权

US06995238B2 Cyclopeptide derivatives 有权
标题翻译：环肽衍生物
公开(公告)号：US06995238B2
公开(公告)日：2006-02-07
申请号：US10183410
申请日：2002-06-28
申请人： Jörg Meyer , Alfred Jonczyk , Berthold Nies , Horst Kessler , Dirk Finsinger , Martin Kantlehner
发明人： Jörg Meyer , Alfred Jonczyk , Berthold Nies , Horst Kessler , Dirk Finsinger , Martin Kantlehner
IPC分类号： C07K5/10
CPC分类号： C07K7/64 , A61K38/00 , Y02P20/125
摘要： Disclosed herein is a process for promoting the integration of a biocompatible device or implant into a tissue of a subject. The process comprises covalently bonding to the surface of the device or implant a compound of the formula I R-Q-X I wherein R is cyclo-(Arg-Gly-Asp-Z), and wherein Q, X and Z are as defined herein.
摘要翻译：本文公开了一种用于促进生物相容性装置或植入物整合到受试者的组织中的方法。该方法包括共价键合至装置的表面或植入化合物

6. 发明授权

US06610826B1 Cyclopeptide derivatives with integrin inhibitor properties 有权
标题翻译：具有整合素抑制剂性质的环肽衍生物
公开(公告)号：US06610826B1
公开(公告)日：2003-08-26
申请号：US09581575
申请日：2000-06-15
申请人： Jörg Meyer , Alfred Jonczyk , Berthold Nies , Horst Kessler , Dirk Finsinger , Martin Kantlehner
发明人： Jörg Meyer , Alfred Jonczyk , Berthold Nies , Horst Kessler , Dirk Finsinger , Martin Kantlehner
IPC分类号： C07K510
CPC分类号： C07K7/64 , A61K38/00 , Y02P20/125
摘要： Compounds of the formula I R—Q—X I, in which R, Q, and X are as defined herein, can be used as integrin inhibitors. In particular, compounds of formula I are suitable for the treatment of disorders caused by implants, defects, inflammations and of osteolytic disorders such as osteoporosis, thrombosis, cardiac infarct and arteriosclerosis. These compounds are also suitable for the acceleration and reinforcement of the integration process of implants and biocompatible surfaces into tissue.
摘要翻译： R，Q和X如本文所定义的式Iin化合物可用作整联蛋白抑制剂。特别地，式I化合物适用于治疗由植入物，缺陷，炎症和溶骨性疾病如骨质疏松症，血栓形成，心肌梗死和动脉硬化引起的疾病。这些化合物也适用于加速和加强植入物和生物相容性表面进入组织的整合过程。

7. 发明授权

US09764057B2 Hydraulic cement-based implant material and use thereof 有权
公开(公告)号：US09764057B2
公开(公告)日：2017-09-19
申请号：US12663052
申请日：2008-06-06
申请人： Berthold Nies
发明人： Berthold Nies
IPC分类号： A61L24/02 , A61L24/00 , A61L27/40 , A61K6/00 , A61K6/06
CPC分类号： A61L24/0084 , A61K6/0008 , A61K6/0023 , A61K6/0067 , A61K6/0643 , A61K6/0675 , A61L24/02 , A61L27/40 , A61L2430/02 , C08L71/02 , C08L33/08
摘要： The invention relates to implant materials that are based on hydraulic cements in the form of one or more pastes, suspensions or dispersions that contain mineral and/or organic and/or organomineral solids and that react, when combined or when reacted with an aqueous liquid, to a solid in a cement-type initiation reaction. The invention also relates to the use of these materials as technical, medical-technical and/or pharmaceutical products, especially as bone cements, bone replacement materials, bone glues, dental filling materials and implantable active ingredient carriers. The implant materials according to the invention in the form of one or more pastes, suspensions or dispersions that contain mineral and/or organic and/or organomineral solids are formulated in an excipient liquid in such a manner that the pastes, suspensions or dispersions are stable in storage at normal conditions over a prolonged period of time and that they react, when combined with an aqueous liquid or when added to an aqueous liquid, in a cement-type initiation reaction and set to a solid. The excipient liquid of the mineral paste, suspension or dispersion is substantially water-free, and water immiscible or insoluble or hardly soluble in water in the chemical sense.

8. 发明授权

US6160033A Process for producing bone cement containing active substances 有权
标题翻译：生产含有活性物质的骨水泥的方法
公开(公告)号：US6160033A
公开(公告)日：2000-12-12
申请号：US242445
申请日：1999-02-17
申请人： Berthold Nies
发明人： Berthold Nies
IPC分类号： A61L27/00 , A61L24/00 , A61L24/06 , A61L27/16 , A61L27/54 , A61K6/087 , A61F2/28 , C08L33/12
CPC分类号： A61L27/54 , A61L24/0015 , A61L24/06 , A61L27/16 , A61L2300/404 , A61L2300/406 , A61L2300/412 , A61L2300/416 , A61L2430/02 , C08L33/06
摘要： The invention relates to a process for the preparation of bone cements comprising active compound and to bone replacement materials or implantable drug depots produced therefrom. The bone cement is composed of a solid component and a liquid component. The liquid component is dissolved in an organic solvent whose proportion does not exceed 50% by weight based on the liquid component, and this solution is mixed with the solid component.
摘要翻译： PCT No.PCT / EP97 / 04434 371日期1999年2月17日 102（e）1999年2月17日PCT PCT 1997年8月13日PCT公布。公开号WO98 / 07456 日期1998年2月26日本发明涉及一种制备包含活性化合物和骨替代材料或由其制备的可植入药物贮库的骨水泥的方法。骨水泥由固体成分和液体成分构成。将液体成分溶解在比例相对于液体成分不超过50重量％的有机溶剂中，将该溶液与固体成分混合。

9. 发明申请

US20120271431A1 Bioactively Coated Metal Implants and Methods for the Production Thereof 审中-公开
标题翻译：生物涂层金属植入物及其生产方法
公开(公告)号：US20120271431A1
公开(公告)日：2012-10-25
申请号：US13394145
申请日：2010-09-03
申请人： Berthold Nies , Stefan Glorius , Sophie Rössler
发明人： Berthold Nies , Stefan Glorius , Sophie Rössler
IPC分类号： A61F2/28 , B05D7/00
CPC分类号： C23C22/22 , A61L27/042 , A61L27/047 , A61L27/32 , C23C22/83
摘要： The invention relates to methods for producing a partial or complete bioactive coating of an iron and/or zinc based metal implant material with calcium phosphates, a bioactively coated iron and/or zinc based metal implant, which is partially or completely coated with calcium phosphates, and bone implants containing an implant material according to the invention. In order to produce the coating according to the invention, iron and/or zinc based metal implant materials are brought in contact with acidic aqueous solutions, which have a pH value of 6.0 or less and contain calcium phosphates, whereby a calcium phosphate layer is deposited on the surface of the implant materials. The iron and/or zinc based metal implant materials, which are used in methods according to the invention, are materials consisting of base iron alloys or pure iron or materials that contain other substances, which are coated with pure iron, with a base iron alloy and/or with zinc.
摘要翻译：本发明涉及用磷酸钙，生物活化涂覆的铁和/或锌基金属植入物制备基于铁和/或锌的金属植入材料的部分或完全生物活性涂层的方法，其部分或完全地被磷酸钙包覆，和含有根据本发明的植入材料的骨植入物。为了制造根据本发明的涂层，使铁和/或锌基金属植入材料与pH值为6.0或更小并含有磷酸钙的酸性水溶液接触，由此沉积磷酸钙层在植入材料的表面上。在根据本发明的方法中使用的铁和/或锌基金属植入材料是由碱铁合金或纯铁组成的材料或其中含有纯铁的其它物质的材料，其中含有铁基合金和/或锌。

10. 发明申请

US20120191214A1 Hydraulic Cement-Based Implant Material and Use Thereof 有权
标题翻译：液压水泥基植入材料及其应用
公开(公告)号：US20120191214A1
公开(公告)日：2012-07-26
申请号：US12663052
申请日：2008-06-06
申请人： Berthold Nies
发明人： Berthold Nies
IPC分类号： A61F2/28
CPC分类号： A61L24/0084 , A61K6/0008 , A61K6/0023 , A61K6/0067 , A61K6/0643 , A61K6/0675 , A61L24/02 , A61L27/40 , A61L2430/02 , C08L71/02 , C08L33/08
摘要： The invention relates to implant materials that are based on hydraulic cements in the form of one or more pastes, suspensions or dispersions that contain mineral and/or organic and/or organomineral solids and that react, when combined or when reacted with an aqueous liquid, to a solid in a cement-type initiation reaction. The invention also relates to the use of these materials as technical, medical-technical and/or pharmaceutical products, especially as bone cements, bone replacement materials, bone glues, dental filling materials and implantable active ingredient carriers. The implant materials according to the invention in the form of one or more pastes, suspensions or dispersions that contain mineral and/or organic and/or organomineral solids are formulated in an excipient liquid in such a manner that the pastes, suspensions or dispersions are stable in storage at normal conditions over a prolonged period of time and that they react, when combined with an aqueous liquid or when added to an aqueous liquid, in a cement-type initiation reaction and set to a solid. The excipient liquid of the mineral paste, suspension or dispersion is substantially water-free, and water immiscible or insoluble or hardly soluble in water in the chemical sense.
摘要翻译：本发明涉及植入材料，其基于含有矿物和/或有机和/或有机矿物固体的一种或多种糊剂，悬浮液或分散体形式的水硬性水泥，并且当与水性液体反应时，在水泥型起始反应中为固体。本发明还涉及这些材料作为技术，医疗技术和/或药物产品，特别是作为骨水泥，骨替代材料，骨胶，牙科填充材料和可植入活性成分载体的用途。将一种或多种含有矿物和/或有机和/或有机矿物质固体的糊剂，悬浮液或分散体形式的根据本发明的植入材料配制在赋形剂液体中，使得糊剂，悬浮液或分散体是稳定的在正常条件下在长时间内储存，并且当与水性液体组合或当加入到水性液体中时，它们在水泥型引发反应中反应并且固化为固体。矿物糊剂，悬浮液或分散体的赋形剂液体基本上是无水的，并且在化学意义上与水不混溶或不溶或难溶于水。

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