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公开(公告)号：US06509318B1
公开(公告)日：2003-01-21
申请号：US09676108
申请日：2000-09-29
IPC分类号： A61K3803
CPC分类号： C07K14/78 , A61K38/00 , C07K14/495
摘要： A family of small peptides have been found to be inhibitory to TGF-&bgr; activity, and preferably have the primary structure of Formula I: AA1-AA2-AA3-Pro-D-Glu-Ala FORMULA I wherein AA1 is leucine, phenylalanine, &agr;-aminoisobutric acid, N-methylalanine, N-methylisoleucine, or isoleucine; AA2 is the same or a different amino acid residue as in AA1; and AA3 is alanine or N-methylalanine.
摘要翻译： 已经发现一小部分小肽对TGF-β活性具有抑制作用，优选具有式I的一级结构：其中AA1是亮氨酸，苯丙氨酸，α-氨基异丁酸，N-甲基丙氨酸，N-甲基异亮氨酸或异亮氨酸; AA2是与AA1相同或不同的氨基酸残基; 而AA3是丙氨酸或N-甲基丙氨酸。
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公开(公告)号：US5780436A
公开(公告)日：1998-07-14
申请号：US742256
申请日：1996-10-31
IPC分类号： A61K47/30 , A61K38/00 , A61K38/22 , A61K47/48 , A61L27/22 , A61P17/02 , A61P25/00 , A61P43/00 , C07K7/06 , C07K14/495 , A61K38/04 , A61K38/08 , C07K5/10
CPC分类号： C07K7/06 , A61L27/227 , C07K14/495 , A61K38/00
摘要： Small peptide mimics of TGF-.beta., having the general sequence AA.sub.i -AA.sub.i+1 -AA.sub.i+2 followed by AA.sub.i+n shortly thereafter, have been prepared. In this sequence, AA.sub.i is alanine, asparagine, or leucine, AA.sub.i+1 is valine or isoleucine, AA.sub.i+2 is alanine, n is 3, 4, or 5 such that there are n-3 amino acid residues in between AA.sub.i+2 and AA.sub.i+n, and AA.sub.i+n is glutamic acid, aspartic acid, glutamine or asparagine. Because the essential requirement for TGF-.beta. activity is the peptide's ability to form a stable .beta.-bend structure under physiologic conditions, the inventive peptides are collectively referred to as .beta.-bend peptides. Compositions for applications such as tissue repair are also provided that comprise a biocompatible matrix having cytomodulin or a cytomodulin analog admixed with or carried by the matrix.
摘要翻译： 已经制备了具有通用序列AAi-AAi + 1-AAi + 2，随后是AAi + n的TGF-β的小肽模拟物。 在该序列中，AAi是丙氨酸，天冬酰胺或亮氨酸，AAi + 1是缬氨酸或异亮氨酸，AAi + 2是丙氨酸，n是3,4或5，使得在AAi + 2之间存在n-3个氨基酸残基 AAi + n，AAi + n为谷氨酸，天冬氨酸，谷氨酰胺或天冬酰胺。 因为TGF-β活性的基本要求是肽在生理条件下形成稳定的β-末端结构的能力，所以本发明的肽统称为β-末端肽。 还提供了诸如组织修复的组合物，其包含具有与基质混合或携带的细胞调节蛋白或细胞模型蛋白类似物的生物相容性基质。
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公开(公告)号：US06638912B2
公开(公告)日：2003-10-28
申请号：US09113696
申请日：1998-07-10
IPC分类号： A61K3807
CPC分类号： A61L27/227 , A61K38/00 , C07K7/06 , C07K14/495 , C07K14/78
摘要： Compositions suitable for pharmaceutical administration are provided in which one compound is a small peptide mimic of TGF-&bgr;. More preferably, pharmaceutical compositions of the present invention are formulated as combinations of two components, wherein one component includes a peptide mimic for TGF-&bgr; and the other component is structurally or biologically analogous to a small region of collagen and mimics the conformation recognized by collagen binding species. A particularly preferred combination is A-N-V-A-E-N-A (SEQ ID NO:1) and G-T-P-G-P-Q-G-I-A-G-Q-R-G-V-V (SEQ ID NO:17).
摘要翻译： 提供了适合于药物给药的组合物，其中一种化合物是TGF-β的小肽模拟物。 更优选地，将本发明的药物组合物配制成两种组分的组合，其中一种组分包括TGF-β的肽模拟物，另一种组分在结构上或生物学上类似于胶原蛋白的小区域并且模拟胶原识别的构象 结合物种。 特别优选的组合是A-N-V-A-E-N-A（SEQ ID NO：1）和G-T-P-G-P-Q-G-I-A-G-Q-R-G-V-V（SEQ ID NO：17）。
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公开(公告)号：US5661127A
公开(公告)日：1997-08-26
申请号：US431954
申请日：1995-05-01
CPC分类号： C07K7/06 , A61L27/227 , C07K14/495 , A61K38/00
摘要： A peptide has been synthesized with the sequence ANVAENA (SEQ ID NO:1). This peptide, designated "cytomodulin," is able to mimic a broad range of activities of TGF-.beta.1 in various cell types. Compositions for applications such as tissue repair are provided that comprise a biocompatible matrix having cytomodulin admixed with or carried by the matrix.
摘要翻译： 已经用序列ANVAENA（SEQ ID NO：1）合成肽。 这种称为“细胞模型调节蛋白”的肽能够模拟各种细胞类型中TGF-β1的广泛活性。 提供了诸如组织修复的组合物，其包含与基质混合或由基质携带的细胞调节蛋白的生物相容性基质。
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公开(公告)号：US06489165B2
公开(公告)日：2002-12-03
申请号：US09760629
申请日：2001-01-16
IPC分类号： C12N500
CPC分类号： A61L27/3817 , A61F2002/30762 , A61F2002/30766 , A61K35/12 , A61L27/3852 , A61L27/3895 , C12N5/0655 , C12N2500/25 , C12N2500/30 , C12N2501/70 , C12N2506/1307 , C12N2533/40 , Y10S623/902 , Y10S623/92
摘要： Fibroblast cells are treated with a chemical inhibitor of protein kinase C such as staurosporine, in conjunction with functionally hypoxic micromass culture so as to be induced into chondrogenic differentiation. Such fibroblast-derived, chondrocyte-like cells may be seeded onto three-dimensional polymer scaffolds for use in the repair of articular cartilage lesions, and thus can obviate the need for invasive techniques to harvest autologous chondrocytes from a limited supply of existing articular cartilage, or to avoid the need for obtaining allogeneic chondrocytes from non-biocompatible donor tissues.
摘要翻译： 成纤维细胞用蛋白激酶C的化学抑制剂如星形孢菌素与功能缺氧微粒培养物一起处理，以诱导成软骨形成分化。 这种成纤维细胞衍生的软骨细胞样细胞可以接种到用于修复关节软骨损伤的三维聚合物支架上，因此可以避免需要有创技术从有限的现有关节软骨供应中收获自体软骨细胞， 或避免从非生物相容性供体组织获得同种异体软骨细胞的需要。
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公开(公告)号：US5958428A
公开(公告)日：1999-09-28
申请号：US859610
申请日：1997-05-20
CPC分类号： A61L27/34 , C07K14/78 , C12N5/0068 , A61K38/00 , A61L2430/02 , C12N2533/30 , C12N2533/50 , C12N2533/54
摘要： Compositions of the invention include composites comprising a biomaterial having compounds thereon with enhanced cell binding with respect to collagen. These composites are useful for soft and hard tissue repair or reconstruction and for in vitro uses. Suitable compounds with enhanced cell binding include synthetic peptides that mimic the conformation necessary for recognition and docking of collagen binding species (such as cell surface receptors for collagen and fibronectin) and have the amino acid residues -Ile-Ala- folded in a .beta.-bend.
摘要翻译： 本发明的组合物包括包含其上具有增强的细胞相对于胶原蛋白结合的化合物的生物材料的复合材料。 这些复合物可用于软组织修复或重建和体外应用。 具有增强的细胞结合的合适的化合物包括模拟胶原结合物质（例如胶原和纤连蛋白的细胞表面受体）的识别和对接所必需的构象的合成肽，并且具有氨基酸残基 - 在β-末端折叠 。
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公开(公告)号：US07199103B2
公开(公告)日：2007-04-03
申请号：US10927517
申请日：2004-08-25
IPC分类号： A61K38/10
CPC分类号： A61L27/34 , A61K38/00 , A61L2430/02 , C07K14/78 , C12N5/0068 , C12N2533/30 , C12N2533/50 , C12N2533/54 , C08L89/06
摘要： Compositions of the invention include composites comprising a biomaterial having compounds thereon with enhanced cell binding with respect to collagen. These composites are useful for soft and hard tissue repair or reconstruction and for in vitro uses. Suitable compounds with enhanced cell binding include synthetic peptides that mimic the conformation necessary for recognition and docking of collagen binding species (such as cell surface receptors for collagen and fibronectin) and have the amino acid residues -Ile-Ala-folded in a β-bend.
摘要翻译： 本发明的组合物包括包含其上具有增强的细胞相对于胶原蛋白结合的化合物的生物材料的复合材料。 这些复合物可用于软组织修复或重建和体外应用。 具有增强的细胞结合的合适的化合物包括模拟胶原结合物质（例如胶原和纤连蛋白的细胞表面受体）的识别和对接所需的构象的合成肽，并具有氨基酸残基 - 在β-弯曲中折叠 。
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公开(公告)号：US5354736A
公开(公告)日：1994-10-11
申请号：US804782
申请日：1991-12-09
IPC分类号： A61K38/00 , A61K38/17 , A61P43/00 , C07K1/00 , C07K7/06 , C07K7/08 , C07K14/00 , C07K14/435 , C07K14/78 , C07K16/00 , C12N5/00 , A61K37/00 , A61K37/02 , C07K5/00 , C07K7/00
CPC分类号： C12N5/0068 , C07K14/78 , A61K38/00 , C12N2533/30 , C12N2533/50 , C12N2533/54
摘要： Compositions of the invention include composites comprising a biomaterial carrying compounds with enhanced cell binding with respect to collagen. These composites are useful for soft and hard tissue repair or reconstruction. Suitable compounds with enhanced cell binding include synthetic peptides that mimic the conformation necessary for recognition and docketing of collagen binding species (such as cell surface receptors for collagen and fibronectin). Hydrogel matrices as the biomaterial promote cell attachment to the matrix and cell migration into the matrix.
摘要翻译： 本发明的组合物包括包含携带具有相对于胶原蛋白增强的细胞结合的化合物的生物材料的复合材料。 这些复合物可用于软组织修复或重建。 具有增强的细胞结合的合适的化合物包括模拟胶原结合物质（例如胶原和纤连蛋白的细胞表面受体）的识别和对接所必需的构象的合成肽。 水凝胶基质作为生物材料促进细胞附着于基质和细胞迁移到基质中。
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公开(公告)号：US06197586B1
公开(公告)日：2001-03-06
申请号：US09204824
申请日：1998-12-03
IPC分类号： C12N500
CPC分类号： A61L27/3817 , A61F2002/30762 , A61F2002/30766 , A61K35/12 , A61L27/3852 , A61L27/3895 , C12N5/0655 , C12N2500/25 , C12N2500/30 , C12N2501/70 , C12N2506/1307 , C12N2533/40 , Y10S623/902 , Y10S623/92
摘要： Fibroblast cells are treated with a chemical inhibitor of protein kinase C such as staurosporine, in conjunction with functionally hypoxic micromass culture so as to be induced into chondrogenic differentiation. Such fibroblast-derived, chondrocyte-like cells may be seeded onto three-dimensional polymer scaffolds for use in the repair of articular cartilage lesions, and thus can obviate the need for invasive techniques to harvest autologous chondrocytes from a limited supply of existing articular cartilage, or to avoid the need for obtaining allogeneic chondrocytes from non-biocompatible donor tissues.
摘要翻译： 成纤维细胞用蛋白激酶C的化学抑制剂如星形孢菌素与功能缺氧微粒培养物一起处理，以诱导成软骨形成分化。 这种成纤维细胞衍生的软骨细胞样细胞可以接种到用于修复关节软骨损伤的三维聚合物支架上，因此可以避免需要有创技术从有限的现有关节软骨供应中收获自体软骨细胞， 或避免从非生物相容性供体组织获得同种异体软骨细胞的需要。
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公开(公告)号：US5674848A
公开(公告)日：1997-10-07
申请号：US285570
申请日：1994-08-03
CPC分类号： C12N5/0068 , A61L27/34 , C07K14/78 , A61K38/00 , A61L2430/02 , C12N2533/30 , C12N2533/50 , C12N2533/54
摘要： Compositions of the invention include packing materials having compounds thereon with enhanced cell binding with respect to collagen. These packing materials are useful for in vitro uses such as for cell culture in bioreactors. Suitable compounds with enhanced cell binding include synthetic peptides that mimic the conformation necessary for recognition and docking of collagen binding species (such as cell surface receptors for collagen and fibronectin) and have the amino acid residues -Ile-Ala- folded in a .beta.-bend.
摘要翻译： 本发明的组合物包括在其上具有相对于胶原蛋白增强的细胞结合的化合物的包装材料。 这些包装材料可用于体外用途，例如用于生物反应器中的细胞培养。 具有增强的细胞结合的合适的化合物包括模拟胶原结合物质（例如胶原和纤连蛋白的细胞表面受体）的识别和对接所必需的构象的合成肽，并且具有氨基酸残基 - 在β-末端折叠 。
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