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1. 发明申请

WO0183522A2 GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING 审中-公开
标题翻译：生长因子改良组织工程蛋白质矩阵
公开(公告)号：WO0183522A2
公开(公告)日：2001-11-08
申请号：PCT/US0011947
申请日：2000-05-01
申请人： ETH ZUERICH , HUBBELL JEFFREY A
发明人： HUBBELL JEFFREY A , SCHENSE JASON C , SAKIYAMA-ELBERT SHELLY E
IPC分类号： A61K31/727 , A61K31/737 , A61K38/17 , A61K47/48 , A61L27/00 , A61L27/20 , A61L27/22 , A61L27/54 , A61L33/00 , A61P41/00 , A61P43/00 , C07K1/04 , C07K14/495 , C07K14/52 , C07K14/745 , C07K19/00 , C07K14/00
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.
摘要翻译：将蛋白质掺入用于组织修复，再生和/或重塑和/或药物递送的蛋白质或多糖基质中。可以掺入蛋白质，使其通过降解基质，通过酶作用和/或扩散来释放。如实施例所示，一种方法是通过共价或非共价方法将肝素与基质结合，形成肝素基质。然后肝素将肝素结合生长因子非共价结合到蛋白质基质上。或者，可以构建融合蛋白，其包含交联区域，例如因子XIIIa底物和天然蛋白质序列。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引入可降解的键可能是特别有用的，其中期望在空间上改变作为再生的功能的药物释放速率，例如快速靠近生物组织界面，并进一步向进入损伤区更慢。额外的益处包括递送系统内的总药物剂量越少，释放的空间调节，允许在最大的细胞活动时释放更多百分比的药物。

2. 发明专利

CA2407952C GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING 未知
公开(公告)号：CA2407952C
公开(公告)日：2007-08-07
申请号：CA2407952
申请日：2000-05-01
申请人： ETH ZUERICH , HUBBELL JEFFREY A
发明人： SCHENSE JASON C , SAKIYAMA-ELBERT SHELLY E , HUBBELL JEFFREY A
IPC分类号： A61L27/54 , A61K31/727 , A61K31/737 , A61K38/17 , A61K47/48 , A61L27/00 , A61L27/20 , A61L27/22 , A61L33/00 , A61P41/00 , A61P43/00 , C07K1/04 , C07K14/495 , C07K14/52 , C07K14/745 , C07K19/00
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 example s, one method is to bind heparin to the matrix by either covalent or non-covale nt methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusio n 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 dr ug release spatially as a function of regeneration, e.g. rapidly near the livin g 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. 发明专利

CA2407952A1 GROWTH FACTOR MODIFIED PROTEIN MATRICES FOR TISSUE ENGINEERING 未知
公开(公告)号：CA2407952A1
公开(公告)日：2001-11-08
申请号：CA2407952
申请日：2000-05-01
申请人： ETH ZUERICH , HUBBELL JEFFREY A
发明人： HUBBELL JEFFREY A , SCHENSE JASON C , SAKIYAMA-ELBERT SHELLY E
IPC分类号： A61K31/727 , A61K31/737 , A61K38/17 , A61K47/48 , A61L27/00 , A61L27/20 , A61L27/22 , A61L27/54 , A61L33/00 , A61P41/00 , A61P43/00 , C07K1/04 , C07K14/495 , C07K14/52 , C07K14/745 , C07K19/00
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 example s, one method is to bind heparin to the matrix by either covalent or non-covale nt methods, to form a heparin-matrix. The heparin then non-covalently binds heparin-binding growth factors to the protein matrix. Alternatively, a fusio n 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 dr ug release spatially as a function of regeneration, e.g. rapidly near the livin g 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.

4. 发明专利

AU4692200A Growth factor modified protein matrices for tissue engineering 未知
公开(公告)号：AU4692200A
公开(公告)日：2001-11-12
申请号：AU4692200
申请日：2000-05-01
申请人： ETH ZUERICH , HUBBELL JEFFREY A
发明人： HUBBELL JEFFREY A , SCHENSE JASON C , SAKIYAMA-ELBERT SHELLY E
IPC分类号： A61K31/727 , A61K31/737 , A61K38/17 , A61K47/48 , A61L27/00 , A61L27/20 , A61L27/22 , A61L27/54 , A61L33/00 , A61P41/00 , A61P43/00 , C07K1/04 , C07K14/495 , C07K14/52 , C07K14/745 , C07K19/00 , C07K14/00

5. 发明专利

CA2371462A1 MODIFIED PROTEIN MATRICES 未知
公开(公告)号：CA2371462A1
公开(公告)日：2001-09-13
申请号：CA2371462
申请日：2000-04-24
申请人： HUBBELL JEFFREY A , ETH ZUERICH
发明人： SCHENSE JASON C , SAKIYAMA-ELBERT SHELLY E , HUBBELL JEFFREY A
IPC分类号： A61K38/00 , A61K38/17 , A61K47/48 , A61L27/20 , A61L27/22 , A61L27/54 , A61P1/16 , A61P9/00 , A61P9/14 , A61P17/00 , A61P25/00 , C07K17/00
摘要： Matrices formed of materials which bind to growth factors, directly or indirectly, are used for controlled delivery of the growth factors, especial ly 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 mos t preferably encourage and promote cellular ingrowth.

6. 发明专利

CA2371462C MODIFIED PROTEIN MATRICES 未知
公开(公告)号：CA2371462C
公开(公告)日：2009-09-15
申请号：CA2371462
申请日：2000-04-24
申请人： HUBBELL JEFFREY A , ETH ZUERICH
发明人： SCHENSE JASON C , SAKIYAMA-ELBERT SHELLY E , HUBBELL JEFFREY A
IPC分类号： A61K38/00 , C07K19/00 , A61K9/00 , A61K38/17 , A61K47/48 , A61L27/20 , A61L27/22 , A61L27/52 , A61L27/54 , A61P1/16 , A61P9/00 , A61P9/14 , A61P17/00 , A61P25/00 , C07K14/475 , C07K14/52 , C07K14/705 , C07K14/755 , C07K14/78 , C07K14/81 , C07K17/00
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 ratio of binding site s to peptides or growth factors can be used to vary the kinetics of the binding, thereby providing a means to increase or decrease the rate of association of the growth factors with the matrix and thus the rate of delivery. A ratio of at least 1:1 heparin to growth factor is preferably used. Increasing the ratio decreases the rate of release. The dissociation kinetics of low affinity heparin-binding proteins are relatively fast, but a high number of binding sites allows rebinding of the growth factor before it can diffuse out of the matrix. Release can occur by diffusion of the growth factor out of the matri x prior to rebinding, or it can occur if the growth factor encounters a cell surface receptor before rebinding to a heparin site. The most preferred matr ix is heparin or peptides containing heparin binding sites bound to fibrin, capable of attaching heparin, a heparin-like polysaccharide, or a heparin-li ke polymer, and a growth factor or peptide fragment thereof having a basic domain that binds heparin. The matrices can be implanted directly, alone or in combination with cells,or implanted and seeded with cells, at a site wher e tissue repair or regeneration is desired. A particularly preferred applicati on 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.

7. 发明专利

AU4488200A Modified protein matrices 未知
公开(公告)号：AU4488200A
公开(公告)日：2001-09-17
申请号：AU4488200
申请日：2000-04-24
申请人： EIDGENOSSISCHE TECHNISCHE HOCHSCHULE ZURICH , HUBBELL JEFFREY A
发明人： HUBBELL JEFFREY A , SCHENSE JASON C , SAKIYAMA-ELBERT SHELLY E
IPC分类号： A61K38/00 , A61K38/17 , A61K47/48 , A61L27/20 , A61L27/22 , A61L27/54 , A61P1/16 , A61P9/00 , A61P9/14 , A61P17/00 , A61P25/00 , C07K17/00
摘要： Matrices that support cell adhesion and growth are disclosed that deliver low heparin-binding affinity growth factor protein peptides in a controlled manner. These matrices comprise covalently or non-covalently bound heparin or heparin-like polymers, which serve to sequester the low heparin-binding affinity growth factor protein peptides within the matrix. The controlled release of some low heparin-binding affinity growth factor or peptides thereof occurs by degradation of some matrix component or dissociation of the low heparin-binding affinity growth factor protein peptides from the bound heparin. This differs from many controlled delivery devices in that release is not controlled solely by diffusion, and the rate of release may therefore be regulated by altering the rate of degradation of the matrix component or the amount of heparin bound within the matrix. The controlled release of such low heparin-binding affinity growth factor proteins such as NGF-beta, NT-3 and BDNF, is demonstrated. The invention also identifies basic domains that can be utilized to identify other low heparin-binding affinity growth factor protein peptides useful in delivery as part of the matrices described herein.

8. 发明专利

DE60042795D1 未知
公开(公告)号：DE60042795D1
公开(公告)日：2009-10-01
申请号：DE60042795
申请日：2000-05-01
申请人： ETH ZUERICH , UNIV ZUERICH
发明人： HUBBELL JEFFREY A , SCHENSE JASON C , SAKIYAMA-ELBERT SHELLY E
IPC分类号： A61L27/54 , A61K31/727 , A61K31/737 , A61K38/17 , A61K47/48 , A61L27/00 , A61L27/20 , A61L27/22 , A61L33/00 , A61P41/00 , A61P43/00 , C07K1/04 , C07K14/495 , C07K14/52 , C07K14/745 , C07K19/00

9. 发明专利

MXPA02010758A MATRICES DE PROTEINA MODIFICADA CON FACTOR DE CRECIMIENTO PARA TEJIDO PRODUCIDO POR INGENIERIA. 未知
公开(公告)号：MXPA02010758A
公开(公告)日：2005-05-31
申请号：MXPA02010758
申请日：2000-05-01
申请人： ETH ZUERICH
发明人： SAKIYAMA-ELBERT SHELLY E
IPC分类号： A61K31/727 , A61K31/737 , A61K38/17 , A61K47/48 , A61L27/00 , A61L27/20 , A61L27/22 , A61L27/54 , A61L33/00 , A61P41/00 , A61P43/00 , C07K1/04 , C07K14/495 , C07K14/52 , C07K14/745 , C07K19/00
摘要： Las proteinas se incorporan en el interior de matrices de proteina o de polisacarido para utilizarse en la reparacion, regeneracion y/o remodelacion de tejidos y/o suministro de farmacos. Las proteinas se pueden incorporar de tal forma que se liberen mediante la degradacion de la matriz, mediante la accion y/o difusion enzimatica. Como se demuestra por los ejemplos, un metodo es unir la heparina a la matriz mediante metodos ya sea covalentes o no covalentes, para formar una matriz de heparina. La heparina luego se une de manera no covalente a los factores de crecimiento por union de heparina a la matriz de proteina. Alternativamente, se puede construir una proteina de fusion que contenga una region degradante tal como por ejemplo, un substrato del factor XIIIa y la secuencia de proteina natural. La incorporacion de enlaces degradables entre la matriz y los factores bioactivos puede ser particularmente util cuando se desea un suministro de farmacos a largo plazo, por ejemplo, en el caso de la regeneracion de nervios, en donde se desea variar la velocidad de la liberacion del farmaco espacialmente como una funcion para regeneracion, por ejemplo, rapidamente cerca de la interfaz de tejido viviente y mas lentamente mas lejos en la zona herida. Los beneficios adicionales incluyen la dosis de farmaco total inferior dentro del sistema de suministro, y una regulacion espacial de liberacion que permite que se libere un mayor a porcentaje del farmaco en el momento de la maxima actividad celular.

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