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公开(公告)号：US5855619A
公开(公告)日：1999-01-05
申请号：US723360
申请日：1996-09-30
IPC分类号： A61L27/00 , A61B17/00 , A61B17/06 , A61B17/11 , A61F2/00 , A61F2/02 , A61F2/08 , A61F2/30 , A61L17/06 , A61L27/38
CPC分类号： A61L27/3834 , A61B17/1146 , A61L17/06 , A61B17/06066 , A61B17/06166 , A61B2017/00004 , A61F2/08 , A61F2/30756 , A61F2/3094 , A61F2/3099 , A61F2002/30062 , A61F2002/30224 , A61F2210/0004 , A61F2230/0069
摘要： An implant for repair of a tissue defect which implant comprises a physiologically compatible load-bearing member having an element for securing under tension tissue adjacent to the defect to be repaired, an element for supporting a tissue reparative cell mass in the defect and a tissue reparative cell mass supported thereby. The implant can be a suture material having a cell containing matrix surrounding a central portion thereof. The matrix is preferably a gel or other material which the cells cause to contract, thereby drawing together the tissues surrounding the defect to which the implant is attached.
摘要翻译： 用于修复组织缺损的植入物，该植入物包括生理上相容的承载构件，其具有用于固定在待修复的缺损位置的紧张组织附近的元件，用于支撑缺损中的组织修复细胞团的元件和组织修复 由此支撑细胞团。 植入物可以是具有围绕其中心部分的包含基质的细胞的缝合材料。 该基质优选是细胞引起收缩的凝胶或其它材料，从而将植入物所附着的缺损周围的组织结合在一起。
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公开(公告)号：US06835377B2
公开(公告)日：2004-12-28
申请号：US09078531
申请日：1998-05-13
申请人： Victor M. Goldberg , Arnold I. Caplan , Francis P. Barry , David J. Fink , Daniel R. Marshak , James S. Burns
发明人： Victor M. Goldberg , Arnold I. Caplan , Francis P. Barry , David J. Fink , Daniel R. Marshak , James S. Burns
IPC分类号： C12N500
CPC分类号： C12N5/0655 , A61K2035/124 , A61K2035/126 , C12N5/0663 , C12N2501/15 , C12N2501/23 , C12N2501/39 , C12N2533/54
摘要： For repair of cartilage damaged as part of the degenerative effects of osteoarthritis, the inventors have found that the human mesenchymal stem cell approach makes it possible to: (1) regenerate both shallow cartilage chondral defects and full thickness cartilage defects (osteochondral lesions); (2) broaden the suitable clinical population to routinely include middle-aged patients; (3) eliminate the use of autologous tissue grafts (mature cartilage and the periosteal covering) to repair an articular cartilage injury; (4) regenerate other types of injured cartilage such as patellar and spinal disk cartilage; (5) regenerate articular joint cartilage in older patients with osteoarthritis; and (6) form new cartilage and subchondral bone which fully integrate into the adjacent normal tissue.
摘要翻译： 为了修复作为骨关节炎退行性疾病的一部分而损伤的软骨，本发明人发现人间充质干细胞方法使得可以：（1）再生浅软骨软骨缺损和全软骨缺损（骨软骨病变）; （2）拓宽适宜的临床人群，常规包括中年患者; （3）消除使用自体组织移植物（成熟软骨和骨膜覆盖物）修复关节软骨损伤; （4）再生其他类型的损伤软骨，如髌骨和脊髓软骨; （5）在老年骨关节炎患者中再生关节软骨; 和（6）形成完全融入相邻正常组织的新软骨和软骨下骨。
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公开(公告)号：US20090274712A1
公开(公告)日：2009-11-05
申请号：US12446836
申请日：2007-10-24
申请人： James E. Dennis , Arnold I. Caplan , David J. Fink
发明人： James E. Dennis , Arnold I. Caplan , David J. Fink
CPC分类号： C07K16/00 , A61K35/12 , A61K47/6901 , C07K16/18 , C07K16/28 , C07K2317/52 , C07K2317/55 , C12N5/0006 , C12N5/0655
摘要： In certain aspects, the invention relates to cell delivery compositions comprising a progenitor cell and a targeting moiety, and methods related thereto. Such compositions and methods may be used, for example, in administering a targeted cell therapy cell therapy to a subject.
摘要翻译： 在某些方面，本发明涉及包含祖细胞和靶向部分的细胞递送组合物及其相关方法。 这样的组合物和方法可以用于例如向受试者施用靶向细胞疗法细胞疗法。
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4.发明授权公开(公告)号：US06174333B1
公开(公告)日：2001-01-16
申请号：US09222688
申请日：1998-12-29
IPC分类号： A61F202
CPC分类号： A61B17/1146 , A61B17/06066 , A61B17/06166 , A61B2017/00004
摘要： An implant for repair of a tissue defect comprises a plurality of physiologically compatible load-bearing sutures for securing under tension tissue adjacent to the defect to be repaired, the sutures for supporting a tissue reparative cell mass in the defect and a tissue reparative cell mass supported thereby. The sutures have a central portion encapsulated in a cell containing matrix which is contracted under a tensile load by the cells thereof and formed into a mat sheet during the contraction. Spring metal wires hold the sutures in tension during the contraction. The matrix is a collagen gel or other material which the cells contract, the cells comprising human mesenchymal stem cells. The mat sheet is then rolled into a spiral roll with the sutures extending from opposite roll ends to form the desired implant. Different embodiments are disclosed.
摘要翻译： 用于修复组织缺损的植入物包括多个生理上相容的承载缝合线，用于固定在待修复的缺损部位的紧张组织附近，用于支撑缺损中的组织修复细胞块的缝线和支撑的组织修复细胞块 从而。 缝线具有封装在含有细胞的基质中的中心部分，该细胞在细胞的拉伸载荷下收缩并在收缩期间形成垫片。 弹簧金属线在收缩期间将缝合线张紧。 基质是胶原凝胶或细胞收缩的其他物质，细胞包含人间充质干细胞。 然后将垫片卷成螺旋卷，其中缝合线从相对的辊端延伸以形成期望的植入物。 公开了不同的实施例。
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公开(公告)号：US08003622B2
公开(公告)日：2011-08-23
申请号：US12893255
申请日：2010-09-29
CPC分类号： C07K5/1016 , A61K48/005 , C07K7/22 , C07K14/67 , C07K14/695 , C07K14/70 , C07K2319/50 , C07K2319/60 , C12N15/86 , C12N2710/16643 , G01N33/6893 , G01N33/9486 , G01N2800/2842
摘要： The invention provides an expression cassette comprising a DNA sequence encoding amino acids 1-99 of human preproenkephalin, a DNA sequence encoding a precursor of a carboxy-amidated peptide flanked by dibasic cleavage sites and optionally a DNA sequence encoding a marker protein (such as Enhanced Green Fluorescent Protein (GFP)) all in operable linkage and under control of a promoter. Where the encoded precursor of a carboxy-amidated peptide is an agonist for an opioid receptor, the invention further provides a method of treating neuropathic pain by administering the gene transfer vector comprising such an expression cassette to a patient. The invention also provides a method for detecting a peptide having a desired effect comprising introducing a library of DNA sequences encoding one or more precursors of carboxy-amidated peptides into host cells; expressing the carboxy-amidated peptides encoded in the library to provide expression products; and screening from the polypeptide expression products for the desired effect.
摘要翻译： 本发明提供了一种表达盒，其包含编码人前脑啡肽的氨基酸1-99的DNA序列，编码侧翼为二碱基切割位点的羧基酰胺化肽的前体的DNA序列和任选的编码标记蛋白的DNA序列（例如增强型 绿色荧光蛋白（GFP））都在可操作的连锁和启动子的控制下。 当羧基酰胺化肽的编码前体是阿片受体的激动剂时，本发明还提供了通过将包含这种表达盒的基因转移载体给予患者来治疗神经性疼痛的方法。 本发明还提供了一种检测具有所需效果的肽的方法，包括将编码羧基酰胺化肽的一种或多种前体的DNA序列文库导入宿主细胞; 表达在文库中编码的羧基酰胺化肽以提供表达产物; 并从多肽表达产物筛选出所需的效果。
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公开(公告)号：US20110112174A1
公开(公告)日：2011-05-12
申请号：US12893255
申请日：2010-09-29
IPC分类号： A61K31/711 , A61P35/00 , A61P29/00 , A61P25/00 , A61P25/04
CPC分类号： C07K5/1016 , A61K48/005 , C07K7/22 , C07K14/67 , C07K14/695 , C07K14/70 , C07K2319/50 , C07K2319/60 , C12N15/86 , C12N2710/16643 , G01N33/6893 , G01N33/9486 , G01N2800/2842
摘要： The invention provides an expression cassette comprising a DNA sequence encoding amino acids 1-99 of human preproenkephalin, a DNA sequence encoding a precursor of a carboxy-amidated peptide flanked by dibasic cleavage sites and optionally a DNA sequence encoding a marker protein (such as Enhanced Green Fluorescent Protein (GFP)) all in operable linkage and under control of a promoter. Where the encoded precursor of a carboxy-amidated peptide is an agonist for an opioid receptor, the invention further provides a method of treating neuropathic pain by administering the gene transfer vector comprising such an expression cassette to a patient. The invention also provides a method for detecting a peptide having a desired effect comprising introducing a library of DNA sequences encoding one or more precursors of carboxy-amidated peptides into host cells; expressing the carboxy-amidated peptides encoded in the library to provide expression products; and screening from the polypeptide expression products for the desired effect.
摘要翻译： 本发明提供了一种表达盒，其包含编码人前脑啡肽的氨基酸1-99的DNA序列，编码侧翼为二碱基切割位点的羧基酰胺化肽的前体的DNA序列和任选的编码标记蛋白的DNA序列（例如增强型 绿色荧光蛋白（GFP））都在可操作的连锁和启动子的控制下。 当羧基酰胺化肽的编码前体是阿片受体的激动剂时，本发明还提供了通过将包含这种表达盒的基因转移载体给予患者来治疗神经性疼痛的方法。 本发明还提供了一种检测具有所需效果的肽的方法，包括将编码羧基酰胺化肽的一种或多种前体的DNA序列文库导入宿主细胞; 表达在文库中编码的羧基酰胺化肽以提供表达产物; 并从多肽表达产物筛选出所需的效果。
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公开(公告)号：US5686262A
公开(公告)日：1997-11-11
申请号：US488368
申请日：1995-06-07
申请人： David J. Fink , Richard S. Brody
发明人： David J. Fink , Richard S. Brody
IPC分类号： A61K38/00 , C07K14/78 , D21H11/14 , D21H17/22 , D21H21/18 , D21H17/00 , C12P21/00 , C12P21/06 , C07K3/12
摘要： The invention includes a method that provides a low cost aqueous solution of solubilized collagen by the steps of: (a) providing an aqueous ground slurry of insoluble collagen and adjusting the pH of said slurry to obtain activity for a proteolytic enzyme added in Step b; (b) adding said proteolytic enzyme to said pH adjusted slurry; (c) reacting the slurry and enzyme of Step b and/or recycled insoluble collagen and enzyme from Step e at a temperature, T, and for a time, t, effective for forming a solution increased in solubilized collagen; (d) adding additional water and insoluble collagen to said solution of Step c and mixing; (e) separating at least some of the solution of Step d containing solubilized collagen from insoluble collagen, whereby at least a portion of said insoluble collagen and proteolytic enzyme is recycled to Step c, and the separated solution containing solubilized collagen is withdrawn as product; an alternative embodiment provides for the direct production of solubilized collagen without the recycle step.
摘要翻译： 本发明包括通过以下步骤提供低成本的溶解胶原水溶液的方法：（a）提供不溶性胶原的水性研磨浆液并调节所述浆液的pH以获得在步骤b中添加的蛋白水解酶的活性; （b）将所述蛋白水解酶加入到所述pH调节浆液中; （c）使步骤b的浆液和酶和/或来自步骤e的再循环不溶性胶原蛋白和酶在温度T下反应一段时间t，以有效形成溶解胶原中增加的溶液; （d）向步骤c的所述溶液中加入额外的水和不溶性胶原并混合; （e）将含有可溶化胶原蛋白的步骤d的至少一部分溶液从不溶性胶原中分离，由此将至少一部分所述不溶性胶原和蛋白水解酶再循环至步骤c，将含有溶解胶原的分离液作为产物取出; 替代实施例提供了直接生产溶解胶原蛋白而没有循环步骤。
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公开(公告)号：US5460967A
公开(公告)日：1995-10-24
申请号：US250803
申请日：1994-05-27
申请人： David J. Fink , Richard S. Brody
发明人： David J. Fink , Richard S. Brody
摘要： The invention includes a method that produces a low cost aqueous solution of solubilized collagen by the steps of: (a) providing an aqueous ground slurry of insoluble collagen and adjusting the pH of said slurry to obtain activity for a proteolytic enzyme added in Step b; (b) adding said proteolytic enzyme to said pH adjusted slurry; (c) reacting the slurry and enzyme of Step b and/or recycled insoluble collagen and enzyme from Step e at a temperature, T, and for a time, t, effective for forming a solution increased in solubilized collagen; (d) adding additional water and insoluble collagen to said solution of Step c and mixing; (e) separating at least some of the solution of Step d containing solubilized collagen from insoluble collagen, whereby at least a portion of said insoluble collagen and proteolytic enzyme is recycled to Step c, and the separated solution containing solubilized collagen is withdrawn as product; an alternative embodiment provides for the direct production of solubilized collagen without the recycle step.
摘要翻译： 本发明包括通过以下步骤产生低成本的溶解胶原水溶液的方法：（a）提供不溶性胶原的水性研磨浆液并调节所述浆液的pH以获得在步骤b中添加的蛋白水解酶的活性; （b）将所述蛋白水解酶加入到所述pH调节浆液中; （c）使步骤b的浆液和酶和/或来自步骤e的再循环不溶性胶原蛋白和酶在温度T下反应一段时间t，以有效形成溶解胶原中增加的溶液; （d）向步骤c的所述溶液中加入额外的水和不溶性胶原并混合; （e）将含有可溶化胶原蛋白的步骤d的至少一部分溶液从不溶性胶原中分离，由此将至少一部分所述不溶性胶原和蛋白水解酶再循环至步骤c，将含有溶解胶原的分离液作为产物取出; 替代实施例提供了直接生产溶解胶原蛋白而没有循环步骤。
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公开(公告)号：US5370692A
公开(公告)日：1994-12-06
申请号：US929449
申请日：1992-08-14
CPC分类号： B29C67/0081 , A61F2/30942 , B29C41/36 , G05B19/4099 , A61C13/0019 , A61F2002/30011 , A61F2002/30948 , A61F2002/30952 , A61F2002/30957 , A61F2002/30968 , A61F2002/3097 , A61F2250/0023 , B29K2105/0002 , B29K2105/0073 , G05B2219/45168 , G05B2219/49017 , G05B2219/49018 , Y10S623/901 , Y10S623/914
摘要： Prosthetic bone implants are fabricated to approximately replicate a patient's original bone. Medical computer aided imaging techniques are applied to generate a data base representing the size and shape of the original bone in a three dimensional coordinate system. The implantable replica is fabricated using the data base and free form manufacturing to sequentially solidify adjoining, cross-sectional intervals of a fluid material. Appropriate fluid materials include ceramic particles which may be selectively bonded by sintering or bonding with a polymer, and a monomer which is polymerized at selected regions by an incident laser beam.
摘要翻译： 制造假体骨植入物以近似复制患者的原始骨骼。 应用医学计算机辅助成像技术来生成表示三维坐标系中原始骨骼的尺寸和形状的数据库。 可植入的复制品使用数据库和自由形式制造来顺序地固化流体材料的相邻的横截面间隔。 合适的流体材料包括陶瓷颗粒，其可以通过与聚合物烧结或粘合而选择性地结合，以及通过入射激光束在选定区域聚合的单体。
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10.发明授权Process for the production of low-cost soluble high-molecular weight collagen 失效生产低成本可溶性高分子量胶原蛋白的方法
公开(公告)号：US5316942A
公开(公告)日：1994-05-31
申请号：US78932
申请日：1993-06-16
申请人： David J. Fink
发明人： David J. Fink
IPC分类号： A61K38/00 , C07K14/78 , D21H11/14 , D21H17/22 , D21H21/18 , C07K3/12 , A61K37/12 , C12N9/99 , C12P21/00
摘要： The invention includes a method that produces a low cost aqueous solution of high molecular weight solubilized collagen by the steps of: (a) providing an aqueous ground slurry of insoluble collagen; (b) adjusting the water or solid content of the wet ground slurry whereby the insoluble collagen is at a concentration that promotes substantially maximum solubilized collagen concentration and molecular weight in a final product; (c) adjusting the pH of the slurry from Step b to obtain activity for a proteolytic enzyme added in Step d; (d) adding the proteolytic enzyme to the pH adjusted slurry and reacting at a temperature, T, and for a time, t, effective for forming high molecualr weight solubilized collagen from the insoluble collagen particles; (e) controlling the reaction conditions for obtaining a high concentration of soluble collagen and a high molecular weight of the solubilized collagen by simultaneously measuring the concentration of solubilized collagen and the molecular weight of the solubilized collagen, whereby the reaction is complete when the molecular weight and the concentration are substantially maximized; and (f) withdrawing the aqueous solution of high molecular weight solubilized collagen as product. Proteolytic enzyme recycle steps are disclosed that can be used to further reduce costs.
摘要翻译： 本发明包括通过以下步骤产生低成本高分子量溶解胶原的水溶液的方法：（a）提供不溶性胶原的水性研磨浆液; （b）调节湿磨浆液的水分或固体含量，由此不溶性胶原蛋白处于最终产品中促进基本上最大溶解的胶原浓度和分子量的浓度; （c）从步骤b调节浆液的pH以获得在步骤d中加入的蛋白水解酶的活性; （d）将蛋白水解酶加入到pH调节的浆液中，并在从不溶性胶原颗粒形成高分子量溶解胶原的温度T和一段时间t反应; （e）通过同时测量溶解的胶原蛋白的浓度和溶解的胶原的分子量来控制获得高浓度可溶性胶原和高分子量的溶解胶原的反应条件，从而当分子量 并且浓度基本上最大化; 和（f）取出高分子量溶解胶原蛋白水溶液作为产品。 公开了可用于进一步降低成本的蛋白水解酶再循环步骤。
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