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1. 发明授权

US5738673A Method and apparatus for sealing implantable, membrane encapsulation devices 失效
标题翻译：用于密封植入式膜封装装置的方法和装置
公开(公告)号：US5738673A
公开(公告)日：1998-04-14
申请号：US476498
申请日：1995-06-07
申请人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
发明人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
IPC分类号： A61M31/00 , A61K9/00 , A61K9/22
CPC分类号： A61K9/0024
摘要： A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33). A method for sealing the implantable encapsulation device (20) is also provided.
摘要翻译：一种用于将生物活性产品或功能扩散到个体的密封的可植入的包封装置（20），其包括基本上无孔的配件（32），其包括限定出入口（34）的内表面（33）。具有内表面（22）的选择性选择性多孔的膜（21）与配合内表面（33）配合以在其间形成储存腔（23）。膜内表面（22）与配件（32）基本上牢固地密封地密封接合以密封空腔（23）。活细胞（24）设置在空腔（23）中，其能够将生物活性产物分泌给个体。膜（21）是能够允许个体与提供生物产物或功能所需的细胞之间的物质通过的材料。插头构件（35）定位在进入口（34）中并且与配件内表面（33）牢固地密封接合。还提供了一种用于密封可植入封装装置（20）的方法。

2. 发明授权

US5653687A Method and apparatus for sealing implantable, membrane encapsulation 失效
标题翻译：用于密封植入式膜封装的方法和装置
公开(公告)号：US5653687A
公开(公告)日：1997-08-05
申请号：US490112
申请日：1995-06-06
申请人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
发明人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
IPC分类号： A61M31/00 , A61K9/00
CPC分类号： A61K9/0024
摘要： A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33). A method for sealing the implantable encapsulation device (20) is also provided.
摘要翻译：一种用于将生物活性产品或功能扩散到个体的密封的可植入的包封装置（20），其包括基本上无孔的配件（32），其包括限定出入口（34）的内表面（33）。具有内表面（22）的选择性选择性多孔的膜（21）与配合内表面（33）配合以在其间形成储存腔（23）。膜内表面（22）与配件（32）基本上牢固地密封地密封接合以密封空腔（23）。活细胞（24）设置在空腔（23）中，其能够将生物活性产物分泌给个体。膜（21）是能够允许个体与提供生物产物或功能所需的细胞之间的物质通过的材料。插头构件（35）定位在进入口（34）中并且与配件内表面（33）牢固地密封接合。还提供了一种用于密封可植入封装装置（20）的方法。

3. 发明授权

US6123700A Method and apparatus for sealing implantable membrane encapsulation devices 失效
标题翻译：用于密封可植入膜包封装置的方法和装置
公开(公告)号：US6123700A
公开(公告)日：2000-09-26
申请号：US016223
申请日：1998-01-30
申请人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
发明人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
IPC分类号： A61M31/00 , A61K9/00 , A61K9/22
CPC分类号： A61K9/0024
摘要： A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33). A method for sealing the implantable encapsulation device (20) is also provided.
摘要翻译：一种用于将生物活性产品或功能扩散到个体的密封的可植入的包封装置（20），其包括基本上无孔的配件（32），其包括限定出入口（34）的内表面（33）。具有内表面（22）的选择性选择性多孔的膜（21）与配合内表面（33）配合以在其间形成储存腔（23）。膜内表面（22）与配件（32）基本上牢固地密封地密封接合以密封空腔（23）。活细胞（24）设置在空腔（23）中，其能够将生物活性产物分泌给个体。膜（21）是能够允许个体与提供生物产物或功能所需的细胞之间的物质通过的材料。插头构件（35）定位在进入口（34）中并且与配件内表面（33）牢固地密封接合。还提供了一种用于密封可植入封装装置（20）的方法。

4. 发明授权

US5653688A Method and apparatus for sealing implantable membrane encapsulation devices 失效
标题翻译：用于密封可植入膜包封装置的方法和装置
公开(公告)号：US5653688A
公开(公告)日：1997-08-05
申请号：US490113
申请日：1995-06-06
申请人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
发明人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
IPC分类号： A61M31/00 , A61K9/00
CPC分类号： A61K9/0024
摘要： A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33). A method for sealing the implantable encapsulation device (20) is also provided.
摘要翻译：一种用于将生物活性产品或功能扩散到个体的密封的可植入的包封装置（20），其包括基本上无孔的配件（32），其包括限定出入口（34）的内表面（33）。具有内表面（22）的选择性选择性多孔的膜（21）与配合内表面（33）配合以在其间形成储存腔（23）。膜内表面（22）与配件（32）基本上牢固地密封地密封接合以密封空腔（23）。活细胞（24）设置在空腔（23）中，其能够将生物活性产物分泌给个体。膜（21）是能够允许个体与提供生物产物或功能所需的细胞之间的物质通过的材料。插头构件（35）定位在进入口（34）中并且与配件内表面（33）牢固地密封接合。还提供了一种用于密封可植入封装装置（20）的方法。

5. 发明授权

US5932460A Method and apparatus for sealing implantable, membrane encapsulation devices containing living cells 失效
标题翻译：用于密封可植入的包含活细胞的膜包封装置的方法和装置
公开(公告)号：US5932460A
公开(公告)日：1999-08-03
申请号：US477308
申请日：1995-06-06
申请人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
发明人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
IPC分类号： A61M31/00 , A61K9/00 , C12N11/04 , A61K9/22 , C12N5/00 , A61E2/00
CPC分类号： A61K9/0024
摘要： A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33). A method for sealing the implantable encapsulation device (20) is also provided.
摘要翻译：一种用于将生物活性产品或功能扩散到个体的密封的可植入的包封装置（20），其包括基本上无孔的配件（32），其包括限定出入口（34）的内表面（33）。具有内表面（22）的选择性选择性多孔的膜（21）与配合内表面（33）配合以在其间形成储存腔（23）。膜内表面（22）与配件（32）基本上牢固地密封地密封接合以密封空腔（23）。活细胞（24）设置在空腔（23）中，其能够将生物活性产物分泌给个体。膜（21）是能够允许个体与提供生物产物或功能所需的细胞之间的物质通过的材料。插头构件（35）定位在进入口（34）中并且与配件内表面（33）牢固地密封接合。还提供了一种用于密封可植入封装装置（20）的方法。

6. 发明授权

US5713887A Method and apparatus for sealing implantable, membrane encapsulation devices 失效
公开(公告)号：US5713887A
公开(公告)日：1998-02-03
申请号：US488560
申请日：1995-06-06
申请人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
发明人： John F. Mills , Edward J. Doherty , Tyrone F. Hazlett , Keith E. Dionne , Nicholas F. Warner , Brian M. Cain , David H. Rein
IPC分类号： A61M31/00 , A61K9/00 , A61K9/22 , A61F2/00
CPC分类号： A61K9/0024
摘要： A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33). A method for sealing the implantable encapsulation device (20) is also provided.

7. 发明授权

US5786216A Inner-supported, biocompatible cell capsules 失效
标题翻译：内支持，生物相容性细胞胶囊
公开(公告)号：US5786216A
公开(公告)日：1998-07-28
申请号：US337555
申请日：1994-11-10
申请人： Keith E. Dionne , Orion D. Hegre , Thomas R. Flanagan , Tyrone F. Hazlett , Edward J. Doherty
发明人： Keith E. Dionne , Orion D. Hegre , Thomas R. Flanagan , Tyrone F. Hazlett , Edward J. Doherty
IPC分类号： A61F2/02 , A61K9/00 , A61K35/12 , B01J13/02 , C12N5/00 , C12N5/071 , C12N11/04 , A61K9/52 , A61K9/50
CPC分类号： A61F2/022 , A61K9/0024 , B01J13/02 , C12N5/0012 , C12N5/0614 , A61K2035/128 , C12N2533/30
摘要： A biocompatible capsule for containing cells for implantation is prepared containing an inner support that provides tensile strength to the capsule. The capsule may be a tubular semipermeable membrane such as a hollow fiber membrane having both ends sealed. A rod shaped inner support extends through the lumen and ends of the rod are attached to sealed ends of the fiber. Prior to sealing one fiber end, cells are introduced into the lumen. Cells within the capsule may be suspended in a liquid medium or immobilized in a hydrogel or extracellular matrix material, and biologically active molecules can be delivered from the capsule to surroundings or from the surroundings into the capsule. The inner support may have external features such as flutes or a roughened or irregularly-shaped surface, and may be coated with cell-adhesive substance or a cell-viability-enhancing substance. The inner support may be a hollow tube having two channels, one communicating with a filling port that permits injecting cells through the support into the capsule and the other communicating with another port that allows gas to escape through the support as cells are introduced. Anti-inflammatory agents can be incorporated into the capsule membrane to reduce immune response, and angiogenic factors and cell growth factors may be used to stimulate cell culture. Post-coating of capsule can be used to provide a protective barrier against immunogens. A tether for capsule retrieval can be formed integral with the inner support.
摘要翻译：制备用于包含用于植入的细胞的生物相容性胶囊，其包含向胶囊提供拉伸强度的内部支撑物。胶囊可以是管状半透膜，例如具有两端密封的中空纤维膜。杆状内部支撑件延伸穿过内腔，杆的端部附接到纤维的密封端。在密封一个纤维端之前，将细胞引入管腔。胶囊内的细胞可以悬浮在液体培养基中或固定在水凝胶或细胞外基质材料中，并且生物活性分子可以从胶囊递送到周围环境或从周围环境进入胶囊。内部支撑件可以具有外部特征，例如凹槽或粗糙或不规则形状的表面，并且可以涂覆有细胞粘附物质或细胞活力增强物质。内部支撑件可以是具有两个通道的中空管，一个与填充口连通，其允许将细胞通过支撑件注入到胶囊中，另一个与另一个端口连通，允许气体在引入电池时通过支撑件逸出。可以将抗炎剂并入胶囊膜中以降低免疫应答，并且血管生成因子和细胞生长因子可用于刺激细胞培养。胶囊的后包衣可用于提供抵抗免疫原的保护性屏障。用于胶囊回收的系绳可以与内部支撑件一体形成。

8. 发明授权

US5773286A Inner supported biocompatible cell capsules 失效
标题翻译：内支持的生物相容性细胞胶囊
公开(公告)号：US5773286A
公开(公告)日：1998-06-30
申请号：US449568
申请日：1995-05-24
申请人： Keith E. Dionne , Orion D. Hegre , Thomas R. Flanagan , Tyrone F. Hazlett , Edward J. Doherty
发明人： Keith E. Dionne , Orion D. Hegre , Thomas R. Flanagan , Tyrone F. Hazlett , Edward J. Doherty
IPC分类号： A61F2/02 , A61K9/00 , A61K35/12 , B01J13/02 , C12N5/00 , C12N5/071 , C12N11/00 , C12N11/04
CPC分类号： A61K9/0024 , A61F2/022 , B01J13/02 , C12N5/0012 , C12N5/0614 , A61K2035/128 , C12N2533/30
摘要： A biocompatible capsule for containing cells for implantation is prepared containing an inner support that provides tensile strength to the capsule. Cells within the capsule are suspended in a liquid medium or immobilized in a hydrogel or extracellular matrix material, and are surrounded by a semipermeable membrane across which biologically active molecules can be delivered from the capsule to surroundings or from the surroundings into the capsule. The inner support may be formed as an integral part of the capsule during a coextrusion process to form the capsule. Alternatively, the inner support may be a discrete component within a tube having top and bottom sealing fittings that are linked withing the tube by the support. The inner support may have external features such as flutes or a roughened or irregularly-shaped surface, and may be coated with cell-adhesive substance or a cell-viability-enhancing substance. The inner support may be a hollow tube having two channels, one communicating with a filling port that permits injecting cells through the support into the capsule and the other communicating with another port that allows gas to escape through the support as cells are introduced. The capsule may be made immunoisolatory by controlling membrane permselectivity or by substances in the membrane that reduce immune response, and may contain a tether for retrieval that can be formed integrally with the inner support.
摘要翻译：制备用于包含用于植入的细胞的生物相容性胶囊，其包含向胶囊提供拉伸强度的内部支撑物。胶囊内的细胞悬浮在液体培养基中或固定在水凝胶或细胞外基质材料中，并且被半透膜围绕，生物活性分子可以从该膜渗透到周围或周围环境或胶囊中。在共挤出过程中，内部支撑可以形成为胶囊的整体部分以形成胶囊。或者，内部支撑件可以是具有顶部和底部密封配件的管内的分立部件，其通过支撑件与管连接。内部支撑件可以具有外部特征，例如凹槽或粗糙或不规则形状的表面，并且可以涂覆有细胞粘附物质或细胞活力增强物质。内部支撑件可以是具有两个通道的中空管，一个与填充口连通，其允许将细胞通过支撑件注入到胶囊中，另一个与另一个端口连通，允许气体在引入电池时通过支撑件逸出。可以通过控制膜选择性或通过减少免疫应答的膜中的物质使胶囊免疫免疫，并且可以包含可与内支架一体形成的用于提取的系绳。

9. 发明授权

US07655257B2 Sustained delivery of an active agent using an implantable system 有权
公开(公告)号：US07655257B2
公开(公告)日：2010-02-02
申请号：US10645293
申请日：2003-08-20
申请人： John R. Peery , Keith E. Dionne , James B. Eckenhoff , Bonnie J. Eckenhoff, legal representative , Felix A. Landrau , Scott D. Lautenbach , Judy A. Magruder , Jeremy C. Wright
发明人： John R. Peery , Keith E. Dionne , James B. Eckenhoff , Felix A. Landrau , Scott D. Lautenbach , Judy A. Magruder , Jeremy C. Wright
IPC分类号： A61K9/20 , A61K9/22 , A61K9/24
CPC分类号： A61M5/14526 , A61K9/0004 , A61K9/0024 , A61K38/09 , A61M2005/14513 , A61M2206/10
摘要： The invention is directed to a device for delivering an active agent formulation for a predetermined administration period. An impermeable reservoir is divided into a water-swellable agent chamber and an active agent formulation chamber. Fluid from the environment is imbibed through a semipermeable plug into the water-swellable agent chamber and the active agent formulation is released through a back-diffusion regulating outlet. Delivery periods of up to 2 years are achieved.

10. 发明授权

US6083523A Implantable biocompatable immunoisolatory vehicle for delivery of selected therapeutic products 有权
标题翻译：用于递送选定治疗产品的可植入生物相容性免疫佐剂
公开(公告)号：US6083523A
公开(公告)日：2000-07-04
申请号：US148671
申请日：1998-09-04
申请人： Keith E. Dionne , Dwaine F. Emerich , Diane Hoffman , Paul R. Sanberg , Lisa Christenson , Orion D. Hegre , David W. Scharp , Paul E. Lacy , Patrick Aebischer , Alfred V. Vasconcellos , Michael J. Lysaght , Frank T. Gentile
发明人： Keith E. Dionne , Dwaine F. Emerich , Diane Hoffman , Paul R. Sanberg , Lisa Christenson , Orion D. Hegre , David W. Scharp , Paul E. Lacy , Patrick Aebischer , Alfred V. Vasconcellos , Michael J. Lysaght , Frank T. Gentile
IPC分类号： A61F2/02 , A61K9/00 , A61K9/48 , A61K9/50 , A61K35/12 , A61K35/30 , A61K35/39 , A61K38/18 , A61K39/395 , A61K47/36 , A61K48/00 , A61L27/00 , C12N5/00 , C12N5/071 , C12N5/077
CPC分类号： A61K9/0092 , A61K35/12 , A61K35/30 , A61K35/39 , A61K38/185 , A61K48/00 , A61K9/0024 , A61K9/4816 , C12N5/0012 , C12N5/0062 , C12N5/0614 , C12N5/0656 , C12N5/0677 , A61K2035/126 , A61K2035/128 , C12N2510/02 , Y10S514/814 , Y10S514/866
摘要： An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual.
摘要翻译：用于植入到产生所需产品或提供所需代谢功能的细胞个体中的免疫分析载体。载体由含有分离的细胞和足以维持细胞的材料的核心区域组成，以及不含分离细胞的选择性选择性生物相容的外周区域，所述细胞免疫分离核心，但提供分泌产物或代谢功能的递送，个人

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