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1. 发明申请

WO2004037311A3 DEVICE AND METHODS FOR SEQUENTIAL, REGIONAL DELIVERY OF MULTIPLE CYTOTOXIC AGENTS 审中-公开
公开(公告)号：WO2004037311A3
公开(公告)日：2004-05-06
申请号：PCT/US2003/033669
申请日：2003-10-21
申请人： KENSEY NASH CORPORATION , BREKKE, John, H. , GUBBE, John, H.
发明人： BREKKE, John, H. , GUBBE, John, H.
IPC分类号： A61L31/04
摘要： An implantable delivery system includes a macrostructure formed of bioresorbable material selected from a group of alphahydroxy acids and defined to include an internal architecture of intercommunicating void spaces. A first cytotoxic agent in the preferred form of cisplatin is joined to the macrostructure during formation. A microstructure in the preferred form of a blend of high molecular weight hyaluronic acid conjugated with a second cytotoxic agent in the preferred form of paclitaxel and of pure high molecular weight hyaluronic acid is invested in the void spaces. Thus, when implanted, the paclitaxel and cisplatin are released sequentially, each initially at high level concentrations followed by lower release. Radiotherapy can be begun after the release of the paclitaxel has been completed but while the cisplatin is being released.

2. 发明申请

WO2003008007A3 DEVICE FOR REGENERATION OF ARTICULAR CARTILAGE AND OTHER TISSUE 审中-公开
公开(公告)号：WO2003008007A3
公开(公告)日：2003-01-30
申请号：PCT/US2002/023156
申请日：2002-07-19
申请人： KENSEY NASH CORPORATION , BREKKE, John, H. , BRADICA, Gino , GOLDMAN, Scott, M.
发明人： BREKKE, John, H. , BRADICA, Gino , GOLDMAN, Scott, M.
IPC分类号： A61L27/50
摘要： An implantable device for facilitating the healing of voids in bone, cartilage and soft tissue is disclosed. A preferred embodiment includes a cartilage region comprising a polyelectrolytic complex joined with a subchondral bone region. The cartilage region, of this embodiment, enhances the environment for chondrocytes to grow articular cartilage; while the subchondral bone region enhances the environment for cells which migrate into that region's macrostructure and which differentiate into osteoblasts. A hydrophobic barrier exists between the regions, of this embodiment. In one embodiment, the polyelectrolytic complex transforms to hydrogel, following the implant procedure.

3. 发明申请

WO1994009722A1 METHOD AND DEVICE FOR RECONSTRUCTION OF ARTICULAR CARTILAGE 审中-公开
标题翻译：用于重建纸张的方法和装置
公开(公告)号：WO1994009722A1
公开(公告)日：1994-05-11
申请号：PCT/US1993010050
申请日：1993-10-20
申请人： THM BIOMEDICAL, INC. , BREKKE, John, H. , COUTTS, Richard, D.
发明人： THM BIOMEDICAL, INC.
IPC分类号： A61F02/28
CPC分类号： A61L27/3804 , A61F2/28 , A61F2/30756 , A61F2/3601 , A61F2/4601 , A61F2002/2817 , A61F2002/2839 , A61F2002/30062 , A61F2002/30261 , A61F2002/30461 , A61F2002/30677 , A61F2002/4649 , A61F2210/0004 , A61F2220/0075 , A61F2230/0082 , A61F2250/0067 , A61L27/3839 , A61L27/3895 , A61L27/48 , A61L27/54 , A61L27/56 , A61L27/58 , A61L2300/414 , A61L2300/604 , A61L27/22 , A61L27/18 , A61L27/20 , C08L67/04
摘要： A biodegradable device for facilitating healing of structural voids in bone, cartilage as well as soft tissue, is disclosed in the most preferred form including a porous macrostructure made from a biodegradable polymer and a chemotactic ground substance in the form of an RGD attachment moiety of fibro-nectin formed as a porous microstructure. For repair of articular cartilage, harvested precursor cells are secured to the biodegradable carrier which is shaped for press fitting into the articular cartilage lesion. In the most preferred form, the chemotactic ground substance enhances the attractiveness of the biodegradable device for cellular attachment at the site of repair and also facilitates the attachment of free, precursor cells such as chondrocytes and bone narrow to the biodegradable device. In the most preferred form, biological modifiers such as transforming growth factor B and basic fibroblastic growth factor are incorporated in the biodegradable device to mediate cellular activity and regulate cellular functions.
摘要翻译：公开了一种可生物降解的装置，用于促进骨，软骨和软组织中的结构空隙的愈合，其中最优选的形式包括由可生物降解的聚合物制成的多孔宏观结构和纤维的RGD附着部分形式的趋化性研磨物质 - 连接蛋白形成为多孔微结构。为了修复关节软骨，收获的前体细胞被固定到可生物降解的载体上，该载体被成形为压配合到关节软骨损伤中。在最优选的形式中，趋化性地面物质增强了生物可降解装置在修复位置处的细胞附着的吸引力，并且还促进游离的前体细胞如软骨细胞和骨窄附着到可生物降解的装置上。在最优选的形式中，将生物修饰剂如转化生长因子B和碱性成纤维细胞生长因子并入可生物降解的装置中以介导细胞活性并调节细胞功能。

4. 发明申请

WO03008007A2 DEVICE FOR REGENERATION OF ARTICULAR CARTILAGE AND OTHER TISSUE 审中-公开
标题翻译：用于再生器官和其他组织的装置
公开(公告)号：WO03008007A2
公开(公告)日：2003-01-30
申请号：PCT/US0223156
申请日：2002-07-19
申请人： KENSEY NASH CORP , BREKKE JOHN H , BRADICA GINO , GOLDMAN SCOTT M
发明人： BREKKE JOHN H , BRADICA GINO , GOLDMAN SCOTT M
IPC分类号： A61F2/00 , A61F2/02 , A61F2/28 , A61F2/30 , A61K35/16 , A61K35/28 , A61K38/15 , A61L27/20 , A61L27/38 , A61L27/56 , A61L27/58 , A61L27/00
CPC分类号： A61F2/28 , A61F2/30756 , A61F2002/30062 , A61F2002/30677 , A61F2210/0004 , A61F2250/0067 , A61K35/16 , A61K35/28 , A61K38/15 , A61L27/20 , A61L27/38 , A61L27/3847 , A61L27/3852 , A61L27/56 , A61L27/58 , A61K2300/00 , C08L5/04
摘要： An implantable device for facilitating the healing of voids in bone, cartilage and soft tissue is disclosed. A preferred embodiment includes a cartilage region comprising a polyelectrolytic complex joined with a subchondral bone region. The cartilage region, of this embodiment, enhances the environment for chondrocytes to grow articular cartilage; while the subchondral bone region enhances the environment for cells which migrate into that region's macrostructure and which differentiate into osteoblasts. A hydrophobic barrier exists between the regions, of this embodiment. In one embodiment, the polyelectrolytic complex transforms to hydrogel, following the implant procedure.
摘要翻译：公开了一种用于促进骨，软骨和软组织中的空隙愈合的可植入装置。优选的实施方案包括包含与软骨下骨区域连接的聚电解质复合物的软骨区域。该实施方案的软骨区域增强软骨细胞生长关节软骨的环境; 而软骨下骨区域增强迁移到该区域的宏观结构中并分化成成骨细胞的细胞的环境。在本实施例的区域之间存在疏水屏障。在一个实施方案中，在植入程序之后，聚电解复合物转化为水凝胶。

5. 发明申请

WO1995011707A1 IMPROVED PROCESS AND DEVICE FOR TREATING AND HEALING A BONE VOID 审中-公开
标题翻译：改进的处理和治疗骨骼失调的装置
公开(公告)号：WO1995011707A1
公开(公告)日：1995-05-04
申请号：PCT/US1994012424
申请日：1994-10-28
申请人： THM BIOMEDICAL, INC. , RINGEISEN, Timothy , BREKKE, John, H.
发明人： THM BIOMEDICAL, INC.
IPC分类号： A61L25/00
CPC分类号： A61L27/54 , A61L24/0015 , A61L24/046 , A61L27/18 , A61L2300/412 , A61L2300/414 , A61L2300/602 , A61L2300/606 , A61L2300/802 , A61L2430/02 , C08L67/04
摘要： An improved method or process and device for treating and healing a bone void is disclosed, and in particular a method employing a surfactant for efficiently incorporating a biologically active agent into the interstices (voids or pores) of a porous hydrophobic biodegradable material wherein the biologically active agent is deposited on the internal surfaces defining the voids or pores of the biodegradable material. The biodegradable body or device, now containing surfactant and a biologically active agent in the body itself as well as on the external surfaces and the internal surfaces defining the voids or pores, is then applied into the bone void or cavity.
摘要翻译：公开了用于治疗和治愈骨空隙的改进的方法或方法和装置，特别是使用表面活性剂有效地将生物活性剂并入多孔疏水生物可降解材料的空隙（空隙或孔隙）中的方法，其中生物活性试剂沉积在限定可生物降解材料的空隙或孔隙的内表面上。然后将现在在体内本身以及外表面和限定空隙或孔的内表面上含有表面活性剂和生物活性剂的可生物降解的身体或装置施加到骨空隙或腔中。

6. 发明申请

WO2005054440A3 A BIOMIMETIC COMPOSITION REINFORCED BY A POLYELECTROLYTIC COMPLEX OF HYALURONIC ACID AND CHITOSAN 审中-公开
标题翻译：由羟基乙酸和壳多糖的聚电解复合物增强的生物组合物
公开(公告)号：WO2005054440A3
公开(公告)日：2005-09-29
申请号：PCT/US2004040051
申请日：2004-12-01
申请人： TISSUE ENGINEERING CONSULTANTS , BREKKE JOHN H
发明人： BREKKE JOHN H
IPC分类号： A61K31/337 , A61K38/18 , A61K45/00 , A61K45/06 , A61L27/26 , A61L27/38 , A61L27/48 , A61L27/54 , C12N20060101 , C12N5/00 , C12N5/08 , C12N11/02 , C12N11/10
CPC分类号： C12N11/10 , A61K31/337 , A61K38/1841 , A61K45/06 , A61L27/26 , A61L27/3834 , A61L27/48 , A61L27/54 , A61L2300/258 , A61L2300/414 , A61L2300/416 , A61L2300/64 , C12N5/0068 , C12N2533/70 , C12N2533/72 , C08L5/08
摘要： The present invention relates to a three dimensional, malleable cell culture composition and method of forming the same comprising hyaluronic acid, chitosan and a polyelectrolytic complex of hyaluronic acid and chitosan. These three components in combination constitute an initial microenvironment for support of stromal cells, and their undifferentiated mesenchymal cell progeny. The tissue engineering device and method of forming the same comprising hyaluronic acid and chitosan and the use of said device with compositions of pluripotent cells and various formulations of cell culture media for repair of tissues is disclosed.
摘要翻译：本发明涉及三维可延展的细胞培养组合物及其形成方法，其包含透明质酸，壳聚糖和透明质酸和壳聚糖的聚电解质复合物。这三个组分组合构成支持基质细胞的初始微环境及其未分化的间充质细胞后代。公开了组合工程装置及其形成方法，其包括透明质酸和壳聚糖，以及使用具有多能细胞组合物的所述装置和用于修复组织的细胞培养基的各种制剂。

7. 发明申请

WO2005054440A2 A BIOMIMETIC COMPOSITION REINFORCED BY A POLYELECTROLYTIC COMPLEX OF HYALURONIC ACID AND CHITOSAN 审中-公开
标题翻译：透明质酸和壳聚糖多功能电解复合物强化的生物活性组合物
公开(公告)号：WO2005054440A2
公开(公告)日：2005-06-16
申请号：PCT/US2004/040051
申请日：2004-12-01
申请人： TISSUE ENGINEERING CONSULTANTS, INC. , BREKKE, John, H.
发明人： BREKKE, John, H.
IPC分类号： C12N
CPC分类号： C12N11/10 , A61K31/337 , A61K38/1841 , A61K45/06 , A61L27/26 , A61L27/3834 , A61L27/48 , A61L27/54 , A61L2300/258 , A61L2300/414 , A61L2300/416 , A61L2300/64 , C12N5/0068 , C12N2533/70 , C12N2533/72 , C08L5/08
摘要： The present invention relates to a three dimensional, malleable cell culture composition and method of forming the same comprising hyaluronic acid, chitosan and a polyelectrolytic complex of hyaluronic acid and chitosan. These three components in combination constitute an initial microenvironment for support of stromal cells, and their undifferentiated mesenchymal cell progeny. The tissue engineering device and method of forming the same comprising hyaluronic acid and chitosan and the use of said device with compositions of pluripotent cells and various formulations of cell culture media for repair of tissues is disclosed.
摘要翻译：本发明涉及包含透明质酸，壳聚糖和透明质酸与壳聚糖的聚电解质复合物的三维可延展细胞培养组合物及其形成方法。这三种成分组合构成初始微环境以支持基质细胞及其未分化的间充质细胞后代。该组织工程装置及其形成方法包括透明质酸和壳聚糖以及所述装置与多能细胞组合物和各种细胞培养基配方在组织修复中的应用。

8. 发明申请

WO2004037311A2 DEVICE AND METHODS FOR SEQUENTIAL, REGIONAL DELIVERY OF MULTIPLE CYTOTOXIC AGENTS 审中-公开
标题翻译：用于顺序，区域递送多种细胞毒剂的装置和方法
公开(公告)号：WO2004037311A2
公开(公告)日：2004-05-06
申请号：PCT/US0333669
申请日：2003-10-21
申请人： KENSEY NASH CORP , BREKKE JOHN H , GUBBE JOHN H
发明人： BREKKE JOHN H , GUBBE JOHN H
IPC分类号： A61K9/22 , A61K31/00 , A61K31/337 , A61K31/728 , A61K33/24 , A61K45/06 , A61L27/20 , A61L27/54 , A61L31/04 , A61L31/16
CPC分类号： A61K33/24 , A61K31/00 , A61K31/337 , A61K31/728 , A61K45/06 , A61L27/20 , A61L27/54 , A61L31/042 , A61L31/16 , A61L2300/224 , A61L2300/416 , A61L2300/602 , A61K2300/00 , C08L5/08
摘要： An implantable delivery system includes a macrostructure formed of bioresorbable material selected from a group of alphahydroxy acids and defined to include an internal architecture of intercommunicating void spaces. A first cytotoxic agent in the preferred form of cisplatin is joined to the macrostructure during formation. A microstructure in the preferred form of a blend of high molecular weight hyaluronic acid conjugated with a second cytotoxic agent in the preferred form of paclitaxel and of pure high molecular weight hyaluronic acid is invested in the void spaces. Thus, when implanted, the paclitaxel and cisplatin are released sequentially, each initially at high level concentrations followed by lower release. Radiotherapy can be begun after the release of the paclitaxel has been completed but while the cisplatin is being released.
摘要翻译：可植入递送系统包括宏观结构，其由选自一组α-羟基酸的生物可吸收材料形成并且被限定为包括内部连通空隙空间的结构。顺铂的优选形式的第一种细胞毒性剂在形成过程中与宏观结构连接。优选形式的与优选形式的紫杉醇和纯高分子量透明质酸共轭的高分子量透明质酸与第二种细胞毒性剂的混合物的优选形式的微观结构被投入到空隙空间中。因此，当植入时，顺序释放紫杉醇和顺铂，每种最初都以高浓度浓度释放，然后释放较低。放疗可在紫杉醇释放完成但顺铂释放后开始。

9. 发明申请

WO1995031157A1 DEVICE AND METHODS FOR IN VIVO CULTURING OF DIVERSE TISSUE CELLS 审中-公开
标题翻译：多样性组织细胞培养的装置和方法
公开(公告)号：WO1995031157A1
公开(公告)日：1995-11-23
申请号：PCT/US1995006109
申请日：1995-05-15
申请人： THM BIOMEDICAL, INC. , BREKKE, John, H. , RINGEISEN, Timothy
发明人： THM BIOMEDICAL, INC.
IPC分类号： A61F02/28
CPC分类号： A61F2/28 , A61F2/30756 , A61F2002/30062 , A61F2002/30677 , A61F2210/0004 , A61F2250/0067 , A61L27/20 , A61L27/54 , C08L5/04 , C08L5/08
摘要： An anatomically specific, bioresorbable, implant device for facilitating the healing of voids in bone, cartilage and soft tissue is disclosed. A preferred embodiment of using the implant device for facilitating the healing of a human joint lesion includes a cartilage region invested with an alginate microstructure joined with a subchondral bone region invested with a hyaluronan microstructure. The alginate selectively dispersed in the cartilage region enhances the environment for chondrocytes to grow articular cartilage. The hyaluronan selectively dispersed in the subchondral bone region enhances the environment for mesenchymal cells which migrate into that region's macrostructure and which differentiate into osteoblasts. The microstructures can be invested at varying concentrations in the regions. A hydrophobic barrier, strategically positioned within the subchondral bone region macrostructure, shields the chondrocytes from the oxygenated blood in subchondral cancellous bone. In the preferred form, the cartilage region includes a tangential zone including a network of intercommunicating void spaces having a horizontal orientation and in communication with synovial fluid and includes a radial zone including multiple void spaces oriented in both horizontal and vertical planes and providing intercommunication between the tangential zone and the subchondral bone region.
摘要翻译：公开了一种用于促进骨，软骨和软组织中的空隙愈合的解剖特异性生物可吸收的植入装置。使用植入装置促进人关节病变愈合的优选实施例包括：投入了与投放有透明质酸微结构的软骨下骨区域连接的藻酸盐微结构的软骨区域。选择性分散在软骨区域的藻酸盐增强软骨细胞生长关节软骨的环境。选择性分散在软骨下骨区域中的透明质酸增强迁移到该区域的宏观结构中并分化成成骨细胞的间充质细胞的环境。微观结构可以在不同浓度的区域投资。位于软骨下骨区域宏观结构内的疏水屏障屏蔽软骨下松质骨中的含氧血液的软骨细胞。在优选形式中，软骨区域包括切向区域，其包括具有水平取向并与滑液连通的相互连通的空隙空间的网络，并且包括在水平和垂直平面中定向的多个空隙空间的径向区域，并且提供切向区和软骨下骨区。

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