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1. 发明授权

EP1465989B1 GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING 有权转让
标题翻译：生长因子修改组织重建PROTEINMATRIZES（组织工程）
公开(公告)号：EP1465989B1
公开(公告)日：2008-02-20
申请号：EP02792510.6
申请日：2002-12-18
申请人： Eidgenossisch Technische Hochschule Zurich , Universität Zürich , Hubbell, Jeffrey A.
发明人： HUBBELL, Jeffrey, A. , LUTOLF, Matthias , SCHENSE, Jason , JEN, Anna
IPC分类号： A61K47/00 , A61K47/48
CPC分类号： A61L27/225 , A61K38/00 , A61L27/227 , C07K14/635 , C07K2319/00
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

2. 发明公开

EP1465989A1 GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING 有权转让
标题翻译：生长因子修改组织重建PROTEINMATRIZES（组织工程）
公开(公告)号：EP1465989A1
公开(公告)日：2004-10-13
申请号：EP02792510.6
申请日：2002-12-18
申请人： Eidgenossisch Technische Hochschule Zurich , Universität Zürich , Hubbell, Jeffrey A.
发明人： HUBBELL, Jeffrey, A. , LUTOLF, Matthias , SCHENSE, Jason , JEN, Anna
IPC分类号： C12N9/10
CPC分类号： A61L27/225 , A61K38/00 , A61L27/227 , C07K14/635 , C07K2319/00
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

3. 发明申请

WO2003052091A1 GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING 审中-公开
标题翻译：生长因子修饰的蛋白质组学工程基因组
公开(公告)号：WO2003052091A1
公开(公告)日：2003-06-26
申请号：PCT/US2002/041114
申请日：2002-12-18
申请人： EIDGENOSSISCH TECHNISCHE HOCHSCHULE ZURICH , UNIVERSITAT ZURICH , HUBBELL, Jeffrey, A.
发明人： HUBBELL, Jeffrey, A. , LUTOLF, Matthias , SCHENSE, Jason , JEN, Anna
IPC分类号： C12N9/10
CPC分类号： A61K9/0024 , A61L27/225 , A61L27/227 , C07K14/635 , C07K2319/00
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.
摘要翻译：将蛋白质掺入蛋白质或多糖基质中用于组织修复，再生和/或重塑和/或药物递送。可以掺入蛋白质，使得它们通过酶促作用和/或扩散而被基质降解释放。如实施例所示，一种方法是通过共价或非共价方法将肝素结合到基质上以形成肝素基质。肝素然后将肝素结合生长因子非共价结合到蛋白质基质上。或者，可以构建含有交联区如融合因子XIIIa底物和天然蛋白质序列的融合蛋白。当需要长期药物递送时，例如在神经再生的情况下，在基质和生物活性因子之间掺入可降解连接可能是特别有用的，其中期望随着再生而在空间上改变药物释放的速率，例如迅速靠近活组织界面并且更慢地进入损伤区域。其他好处包括输送系统内总的药物剂量较低，释放的空间调节允许在最大的细胞活性时释放更大百分比的药物。

4. 发明公开

EP1280566A2 GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING 有权
标题翻译： DIES由改性生长因子织物机构
公开(公告)号：EP1280566A2
公开(公告)日：2003-02-05
申请号：EP00928733.5
申请日：2000-05-01
申请人： Eidgenossisch Technische Hochschule Zurich , Hubbell, Jeffrey A.
发明人： HUBBELL, Jeffrey, A. , SCHENSE, Jason, C. , SAKIYAMA-ELBERT, Shelly, E.
IPC分类号： A61L27/54 , A61L27/22 , A61L27/20 , A61K47/48
CPC分类号： A61L27/20 , A61K47/61 , A61K47/62 , A61L27/227 , A61L27/54 , A61L2300/236 , A61L2300/252 , A61L2300/414 , A61L2300/604
摘要： Proteins are incorporated into protein or polysaccharide matrices for use in tissue repair, regeneration and/or remodeling and/or drug delivery. The proteins can be incorporated so that they are released by degradation of the matrix, by enzymatic action and/or diffusion. As demonstrated by the examples, one method is to bind heparin to the matrix by either covalent or non-covalent methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusion protein can be constructed which contains a crosslinking region such as a factor XIIIa substrate and the native protein sequence. Incorporation of degradable linkages between the matrix and the bioactive factors can be particularly useful when long-term drug delivery is desired, for example in the case of nerve regeneration, where it is desirable to vary the rate of drug release spatially as a function of regeneration, e.g. rapidly near the living tissue interface and more slowly farther into the injury zone. Additional benefits include the lower total drug dose within the delivery system, and spatial regulation of release which permits a greater percentage of the drug to be released at the time of greatest cellular activity.

5. 发明公开

EP1175235A1 MODIFIED PROTEIN MATRICES 审中-公开
标题翻译：修饰蛋白基质
公开(公告)号：EP1175235A1
公开(公告)日：2002-01-30
申请号：EP00926336.9
申请日：2000-04-24
申请人： Eidgenossisch Technische Hochschule Zurich , Hubbell, Jeffrey A.
发明人： HUBBELL, Jeffrey, A. , SCHENSE, Jason, C. , SAKIYAMA-ELBERT, Shelly, E.
IPC分类号： A61L27/54 , A61L27/20 , A61L27/22
CPC分类号： A61L27/20 , A61K47/62 , A61K47/6903 , A61L27/227 , A61L27/54 , A61L2300/25 , A61L2300/252 , A61L2300/414 , A61L2300/602
摘要： Matrices formed of materials which bind to growth factors, directly or indirectly, are used for controlled delivery of the growth factors, especially for use in tissue repair and/or regeneration. The matrices may have heparin bound thereto ionically or covalently, or heparin-like binding sites incorporated in the matrix forming materials. The heparin or heparin-like binding sites can bind to the growth factors. The matrices can be implanted directly, alone or in combination with cells, or implanted and seeded with cells, at a site where tissue repair or regeneration is desired. A particularly preferred application is in regeneration and repair of nerves. The matrices can be coated on medical devices and implants. The matrices most preferably encourage and promote cellular ingrowth.
摘要翻译：由直接或间接结合生长因子的材料形成的基质被用于生长因子的受控递送，尤其用于组织修复和/或再生。基质可以具有离子或共价结合的肝素或掺入基质形成材料中的肝素样结合位点。肝素或肝素样结合位点可以与生长因子结合。基质可以直接植入，单独植入或与细胞联合植入，或植入细胞并接种于希望进行组织修复或再生的部位。特别优选的应用是神经的再生和修复。矩阵可以涂在医疗器械和植入物上。基质最优选促进和促进细胞向内生长。

6. 发明授权

EP1107802B1 GELS AND MULTILAYER SURFACE STRUCTURES FROM BORONIC ACID CONTAINING POLYMERS 有权
标题翻译： GELS和多层表面结构硼酸含氯聚合物的
公开(公告)号：EP1107802B1
公开(公告)日：2004-10-13
申请号：EP99943966.4
申请日：1999-08-27
申请人： Eidgenössische Technische Hochschule Zürich , Hubbell, Jeffrey A.
发明人： HUBBELL, Jeffrey, A. , ELBERT, Donald, L. , WINBLADE, Natalie, D.
IPC分类号： A61L31/08 , A61L27/28
CPC分类号： A61L31/10 , A61L27/34 , A61L29/085 , C08L71/02
摘要： Boronic acid containing polymers are used to form bioinert gels and multilayer surface structures. These polymers form cross-linked hydrogels, which are highly swollen in water. The cross-linking can either be chemical or physical. Water soluble polymers containing boronic acid groups, such as phenylboronic acid (PBA), can be physically cross-linked by mixing the polymers in water with other polymers containing hydroxyls or carboxylic acids. Alternatively, surfaces can be treated by stepwise incubation with a solution of the boronic acid containing polymer, followed by incubation with a solution of a diol or carboxylic acid containing polymer. Many successive layers can be generated, increasing the thickness of the formed structure at each step. The bioinert gel or surface coating can be used for passivating the surfaces of medical implants (especially those based on transplanted tissue), or for passivating the surfaces of tissues in situ, decreasing the incidence or severity of such pathologic conditions as the formation of post-surgical adhesions, and thrombosis following angioplasty.

7. 发明公开

EP1190252A1 POLYIONIC COATINGS IN ANALYTIC AND SENSOR DEVICES 有权
标题翻译：聚离子涂料分析设备和传感器
公开(公告)号：EP1190252A1
公开(公告)日：2002-03-27
申请号：EP00928641.0
申请日：2000-04-28
申请人： Eidgenössische Technische Hochschule Zürich , Hubbell, Jeffrey A.
发明人： HUBBELL, Jeffrey, A. , TEXTOR, Marcus , ELBERT, Donald, L. , FINKEN, Stephanie , RUIZ-TAYLOR, Laurence , SPENCER, Nicholas, D. , HOFER, Rolf
IPC分类号： G01N33/543 , G01N33/551 , A61L31/10
CPC分类号： B82Y30/00 , A61B5/14546 , A61B5/1459 , A61L27/34 , A61L31/10 , G01N33/54373 , G01N33/54393 , G01N33/551 , Y10S435/815 , Y10S435/961 , Y10S435/969 , Y10S436/819 , Y10S436/823
摘要： Multifunctional, polyionic copolymers are synthesized on/or applied to substrate surfaces for analytical and sensing purposes, the coatings being particularly useful for suppression of non-specific interaction, adsorption or attachment. Groups can be coupled to, integrated into or absorbed to the multifunctional polymer that are able to recognize, interact with and bind specifically to target analyte molecules. These materials can also be used to modulate biological interactions upon substrate surfaces for use as selective implant surfaces that resist cell attachment and may optionally promote the attachment of specific cell types or induce a particular cellular behaviour. The multifunctional polymer coatings typically include brush copolymers based on a polycationic or polyanionic backbone with side chains that control interaction with the environment, such as poly(ethylene glycol) or poly(ethylene oxide)-based side chains that decrease cellular adhesion, and analyte-specific side chains.

8. 发明公开

EP1107802A1 GELS AND MULTILAYER SURFACE STRUCTURES FROM BORONIC ACID CONTAINING POLYMERS 有权
标题翻译： GELS和多层表面结构硼酸含氯聚合物的
公开(公告)号：EP1107802A1
公开(公告)日：2001-06-20
申请号：EP99943966.4
申请日：1999-08-27
申请人： Eidgenössische Technische Hochschule Zürich , Hubbell, Jeffrey A.
发明人： HUBBELL, Jeffrey, A. , ELBERT, Donald, L. , WINBLADE, Natalie, D.
IPC分类号： A61L31/08 , A61L27/28
CPC分类号： A61L31/10 , A61L27/34 , A61L29/085 , C08L71/02
摘要： Boronic acid containing polymers are used to form bioinert gels and multilayer surface structures. These polymers form cross-linked hydrogels, which are highly swollen in water. The cross-linking can either be chemical or physical. Water soluble polymers containing boronic acid groups, such as phenylboronic acid (PBA), can be physically cross-linked by mixing the polymers in water with other polymers containing hydroxyls or carboxylic acids. Alternatively, surfaces can be treated by stepwise incubation with a solution of the boronic acid containing polymer, followed by incubation with a solution of a diol or carboxylic acid containing polymer. Many successive layers can be generated, increasing the thickness of the formed structure at each step. The bioinert gel or surface coating can be used for passivating the surfaces of medical implants (especially those based on transplanted tissue), or for passivating the surfaces of tissues in situ, decreasing the incidence or severity of such pathologic conditions as the formation of post-surgical adhesions, and thrombosis following angioplasty.

9. 发明申请

WO2010002450A2 MICELLES FOR DELIVERY OF NITRIC OXIDE 审中-公开
标题翻译：用于递送一氧化氮的胶束
公开(公告)号：WO2010002450A2
公开(公告)日：2010-01-07
申请号：PCT/US2009/003885
申请日：2009-06-30
申请人： ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE , HUBBELL, Jeffrey, A. , JO, Yun, Suk , VAN DER VLIES, Andre
发明人： HUBBELL, Jeffrey, A. , JO, Yun, Suk , VAN DER VLIES, Andre
IPC分类号： A61K9/127 , A61K33/00 , A61K47/34 , A61P9/10
CPC分类号： A61K31/77 , A61K9/1075 , A61K9/1273 , A61K31/787 , A61K31/80 , A61K47/48176 , A61K47/488 , A61K47/58 , A61K47/6907 , Y10S977/906
摘要： Embodiments include a vehicle for delivery of nitric oxide comprising: a collection of micelles having an internal micelle core that comprises a polymer with N-diazeniumdiolate comprising NO complexed with secondary amines of the polymer. Embodiments include a method of making a nitric oxide vehicle comprising dissolving a polymer that comprises secondary amines in an aqueous solution and combining the polymer with nitric oxide in the solution to form a N-diazeniumdiolate comprising the nitric oxide complexed with the secondary amines, with the formation of the N-diazeniumdiolate causing the polymer to be at least partially insoluble in the solution and to form a collection of micelles that have an internal core that comprises N-diazeniumdiolate.
摘要翻译：实施方案包括用于递送一氧化氮的媒介物，其包含：具有内部胶束核心的胶束集合体，所述内部胶束核心包含具有包含与聚合物的仲胺络合的NO的N-二醇二氮烯鎓的聚合物。实施方案包括制备一氧化氮载体的方法，所述方法包括将包含仲胺的聚合物溶解在水溶液中并且将聚合物与一氧化氮在溶液中结合以形成包含与仲胺络合的一氧化氮的N-二醇二氮烯鎓， N-二醇二氮烯鎓的形成导致聚合物至少部分不溶于溶液中并形成具有包含N-二氮烯鎓二醇化物的内核的胶束集合。

10. 发明申请

WO2007015782A1 MOLECULAR VARIANT FIBRINOGEN FUSION PROTEINS 审中-公开
标题翻译：分子变体纤维蛋白融合蛋白
公开(公告)号：WO2007015782A1
公开(公告)日：2007-02-08
申请号：PCT/US2006/027559
申请日：2006-07-14
申请人： ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE , HUBBELL, Jeffrey, A. , BARKER, Thomas, A.
发明人： HUBBELL, Jeffrey, A. , BARKER, Thomas, A.
IPC分类号： C12N15/62 , C07K14/75 , A61K38/36
CPC分类号： C12N15/62 , A61K38/00 , C07K14/75
摘要： Fibrinogen fusion proteins, methods of making, and methods of using fibrinogen fusion proteins are described. In a preferred embodiment the fibrinogen fusion protein contains a truncated Aα chain of fibrinogen. The Aα chain contains truncation site, which is a deletion of amino acids at its C-terminal region. A non-fibrinogen protein or peptide is C-terminally attached to the truncation site. The fibrinogen fusion proteins can be used alone or mixed with native fibrinogen to form fibrin polymer.
摘要翻译：描述了纤维蛋白原融合蛋白，制备方法和使用纤维蛋白原融合蛋白的方法。在优选的实施方案中，纤维蛋白原融合蛋白含有纤维蛋白原的截短的Aa链。 Aa链含有截短位点，其是在C末端区域缺失氨基酸。非纤维蛋白原蛋白或肽与截短位点C-末端连接。纤维蛋白原融合蛋白可以单独使用或与天然纤维蛋白原混合形成纤维蛋白聚合物。

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