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1. 发明授权

US5011472A Implantable delivery system for biological factors 失效
标题翻译：生物因子植入式输送系统
公开(公告)号：US5011472A
公开(公告)日：1991-04-30
申请号：US240939
申请日：1988-10-06
申请人： Patrick Aebischer , Pierre M. Galletti , George Panol , Luigi Miracoli
发明人： Patrick Aebischer , Pierre M. Galletti , George Panol , Luigi Miracoli
IPC分类号： A61F2/02 , A61M5/142
CPC分类号： A61M5/14276 , A61F2/022 , A61M2205/3523
摘要： Devices and methods are disclosed to provide hybrid, modular systems for the constitutive delivery of appropriate dosages of active factor to a subject and, in some instances, to specific anatomical regions of the subject. The systems include a cell reservoir containing living cells capable of secreting an active agent, which is preferably adapted for implantation within the body of the subject and further includes at least one semipermeable membrane, whereby the transplanted cells can be nourished by nutrients transported across the membrane while at the same time protected from immunological, bacterial, and viral assault. The systems further include a pumping means, which can be implantable or extracorporeal, for drawing a body fluid from the subject into the cell reservoir and for actively transporting the secreted biological factors from the cell reservoir to a selected region of the subject.
摘要翻译：公开了装置和方法以提供混合模块化系统，用于将主动因子的合适剂量的组成型递送给受试者，并且在某些情况下提供给对象的特定解剖区域。该系统包括含有能够分泌活性剂的活细胞的细胞储库，其优选适于植入受试者的身体内并且还包括至少一种半透膜，由此可以通过跨膜运送的营养物滋养移植的细胞同时保护免受免疫，细菌和病毒攻击。所述系统还包括可植入或体外的抽吸装置，用于将体液从受试者吸入细胞储存器中并用于将分泌的生物因子从细胞储存器积极输送到受试者的选定区域。

2. 发明授权

US4878913A Devices for neural signal transmission 失效
标题翻译：神经信号传输装置
公开(公告)号：US4878913A
公开(公告)日：1989-11-07
申请号：US93371
申请日：1987-09-04
申请人： Patrick Aebischer , Robert F. Valentini , Pierre M. Galletti
发明人： Patrick Aebischer , Robert F. Valentini , Pierre M. Galletti
IPC分类号： A61F2/72
CPC分类号： A61F2/72
摘要： Devices and methods for transmitting neural signals from a proximal stump of a transected nerve to a prosthetic apparatus are disclosed employing microelectrodes, preferably conductive fiber networks, capable of sensing electrical signals from a nerve and transmitting such signals to a prosthetic apparatus; and a semipermeable guidance channel disposed about the microelectrodes. The channels include an opening adapted to receive the proximal stump of a transected nerve, such that the channel promotes the growth of the stump and the formation of an electrical connection between the transected nerve and the microelectrode.

3. 发明授权

US4877029A Semipermeable nerve guidance channels 失效
标题翻译：半透明神经引导通道
公开(公告)号：US4877029A
公开(公告)日：1989-10-31
申请号：US32489
申请日：1987-03-30
申请人： Robert F. Valentini , Patrick Aebischer , Pierre M. Galletti
发明人： Robert F. Valentini , Patrick Aebischer , Pierre M. Galletti
IPC分类号： A61B17/00 , A61B17/11 , A61B19/00 , A61F2/00 , A61L27/26
CPC分类号： A61B17/1128 , A61L27/26 , A61B17/00491 , A61B2017/00004 , A61F2002/30235 , A61F2230/0069 , A61L2430/32
摘要： Medical devices employing semipermeable materials, such as acrylic copolymers, polyurethane isocyanate, and other biocompatible semipermeable polymers, are disclosed for use as guidance channels in regenerating nerves. The devices can be formed by tubular semipermeable conduits adapted to receive the ends of a severed or damaged nerve. The tubular conduits define lumens through which axons can regenerate to restore motor and/or sensory functions. The guidance materials are chosen such that they are capable of allowing the diffusion of nutrients and other metabolites to the regenerating nerve site while excluding fibroblasts and other scar-forming cells. In particular, tubular channels which have a smooth inner surface and longitudinally oriented trabeculae result in significantly larger regenerated nerve cables and higher numbers of regenerated myelinated axons.

4. 再颁专利

USRE35653E In vivo delivery of neurotransmitters by implanted, encapsulated cells 失效
标题翻译：通过植入的包封细胞体内递送神经递质
公开(公告)号：USRE35653E
公开(公告)日：1997-11-04
申请号：US85504
申请日：1993-06-30
申请人： Patrick Aebischer , Shelley R. Winn , Pierre M. Galletti
发明人： Patrick Aebischer , Shelley R. Winn , Pierre M. Galletti
IPC分类号： A61M37/00 , A61F2/02 , A61K9/00 , A61K9/22 , A61K9/48 , A61K9/50 , A61K9/52 , A61K35/12 , A61K35/22 , A61K35/30 , A61M31/00 , B01J13/02 , C12N5/00 , C12N5/071 , C12N5/0793 , C12N11/04
CPC分类号： A61K9/0092 , A61F2/022 , A61K35/22 , A61K35/30 , A61K9/0024 , A61K9/0085 , A61M31/002 , B01J13/02 , C12N11/04 , C12N5/0012 , C12N5/0614 , C12N5/0619 , A61M2210/0687 , A61M2210/0693 , C12N2533/30
摘要： Methods and devices are disclosed for the delivery of a neurotransmitter from an implanted, neurotransmitter-secreting cell culture to a target region in a subject. The cell culture is maintained within a biocompatible, semipermeable membrane which permits the diffusion of the neurotransmitter therethrough while excluding viruses, antibodies, and other detrimental agents present in the external environment from gaining access. Implantable cell culture devices are disclosed, some of which may be retrieved from the subject, replaced or recharged with new, neurotransmitter-secreting cell cultures, and reimplanted.
摘要翻译：公开了用于将神经递质从植入的神经递质分泌细胞培养物递送至受试者的靶区域的方法和装置。细胞培养物保持在生物相容的半透膜中，其允许神经递质的扩散通过，同时排除存在于外部环境中的病毒，抗体和其它有害物质以获得通路。公开了可植入细胞培养装置，其中一些可以从受试者中取出，用新的神经递质分泌细胞培养物替代或再充电并重新植入。

5. 发明授权

US4892538A In vivo delivery of neurotransmitters by implanted, encapsulated cells 失效
标题翻译：通过植入的包封细胞体内递送神经递质
公开(公告)号：US4892538A
公开(公告)日：1990-01-09
申请号：US121626
申请日：1987-11-17
申请人： Patrick Aebischer , Shelley R. Winn , Pierre M. Galletti
发明人： Patrick Aebischer , Shelley R. Winn , Pierre M. Galletti
IPC分类号： A61M37/00 , A61F2/02 , A61K9/00 , A61K9/22 , A61K9/48 , A61K9/50 , A61K9/52 , A61K35/12 , A61K35/22 , A61K35/30 , A61M31/00 , B01J13/02 , C12N5/00 , C12N5/071 , C12N5/0793 , C12N11/04
CPC分类号： A61K9/0092 , A61F2/022 , A61K35/22 , A61K35/30 , A61K9/0024 , A61K9/0085 , A61M31/002 , B01J13/02 , C12N11/04 , C12N5/0012 , C12N5/0614 , C12N5/0619 , A61M2210/0687 , A61M2210/0693 , C12N2533/30
摘要： Methods and devices are disclosed for the delivery of a neurotransmitter from an implanted, neurotransmitter-secreting cell culture to a target region in a subject. The cell culture is maintained within a biocompatible, semipermeable membrane which permits the diffusion of the neurotransmitter therethrough while excluding viruses, antibodies, and other detrimental agents present in the external environment from gaining access. Implantable cell culture devices are disclosed, some of which may be retrieved from the subject, replaced or recharged with new, neurotransmitter-secreting cell cultures, and reimplanted.
摘要翻译：公开了用于将神经递质从植入的神经递质分泌细胞培养物递送至受试者的靶区域的方法和装置。细胞培养物保持在生物相容的半透膜中，其允许神经递质的扩散通过，同时排除存在于外部环境中的病毒，抗体和其它有害物质以获得通路。公开了可植入细胞培养装置，其中一些可以从受试者中取出，用新的神经递质分泌细胞培养物替代或再充电并重新植入。

6. 发明授权

US6140089A Chitosan core matrix containing cells encapsulated in a thermoplastic semipermeable membrane 失效
标题翻译：壳聚糖核心基质含有包封在热塑性半透膜中的细胞
公开(公告)号：US6140089A
公开(公告)日：2000-10-31
申请号：US251004
申请日：1999-02-16
申请人： Patrick Aebischer , Beth A. Zielinski
发明人： Patrick Aebischer , Beth A. Zielinski
IPC分类号： A61K35/12 , A61L27/20 , A61L27/38 , C12N5/077 , C12N5/0793 , C12N11/10 , C12N11/04 , C12N5/00
CPC分类号： C12N5/0012 , A61L27/20 , A61L27/38 , A61L27/3804 , C12N5/0618 , C12N5/0619 , A61K2035/128 , A61K35/12
摘要： Encapsulated viable cells for implanting are prepared having cells dispersed in a particulate, essentially non cross-linked chitosan core matrix that is enclosed within a semipermeable membrane. The cells are entrapped between chitosan particles of the core matrix and there is essentially no interfacial cross-linking between the core matrix and the membrane. The core matrix provides a physical support for the cells such that the cells are evenly dispersed throughout the core matrix so as to allow their maintenance, growth, proliferation and differentiation. The encapsulated cells may be prepared by mixing viable cells with a solution of chitosan, encapsulating the resultant mixture in a thermoplastic semipermeable membrane, and causing the chitosan to precipitate such as by changing the pH to form the core matrix. Alternatively, the chitosan in solution is precipitated to form the core matrix containing cells, and the core matrix is encapsulated in a semipermeable membrane. Cells encapsulated include neurosecretory cell lines, .beta.-cell-derived cells lines, fibroblasts, myocytes and glial cells.
摘要翻译：制备用于植入的包封的活细胞，其具有分散在颗粒状基本上非交联壳聚糖核心基质中的细胞，其被包封在半透膜内。细胞被截留在核心基质的壳聚糖颗粒之间，并且核心基质和膜之间基本上没有界面交联。核心基质为细胞提供物理支持，使得细胞均匀地分散在整个核心基质中，以便使其维持，生长，增殖和分化。包封的细胞可以通过将活细胞与壳聚糖溶液混合，将所得混合物包封在热塑性半透膜中并使壳聚糖沉淀，例如通过改变pH以形成核心基质来制备。或者，将溶液中的壳聚糖沉淀以形成含核心基质的细胞，并将核心基质包封在半透膜中。包封的细胞包括神经分泌细胞系，β-细胞来源的细胞系，成纤维细胞，肌细胞和神经胶质细胞。

7. 发明授权

US6080412A Pharmaceutical microencapsulation 失效
标题翻译：药物微胶囊化
公开(公告)号：US6080412A
公开(公告)日：2000-06-27
申请号：US162590
申请日：1998-09-29
申请人： Olivier Jordan , Patrick Aebischer , Jean-Francois Clemence
发明人： Olivier Jordan , Patrick Aebischer , Jean-Francois Clemence
IPC分类号： A61K9/50 , A61K35/12 , A61L27/00 , A61L27/38 , C12N5/071 , C12N11/04 , C07K1/00
CPC分类号： A61L27/3804 , A61K9/5026 , A61K9/5089 , C12N11/04 , C12N5/0677 , A61K2035/128
摘要： A method of producing a microencapsulated pharmaceutical formulation is disclosed comprising causing a dye to be attached to the surface of pharmaceutical particles or particle clusters and applying a source of radiant energy to the dye in the presence of a liquid polymeric or polymerisable material so as to cause the material to cross-link, producing a conformal layer of cross-linked polymer on the particulate surfaces. Preferably, the polymer provides an immuno-protective layer around the particles, while allowing therapeutic components to exit the microcapsules. Microencapsulated pharmaceutical formulations and their medical use are also disclosed, especially for the treatment of diabetes by encapsulating insulin secreting cells.
摘要翻译：公开了一种生产微胶囊化药物制剂的方法，其包括使染料附着在药物颗粒或颗粒簇的表面上，并在液体聚合或可聚合材料的存在下将辐射能源施加到染料上，从而引起交联的材料，在颗粒表面上产生交联聚合物的共形层。优选地，聚合物在颗粒周围提供免疫保护层，同时允许治疗成分离开微胶囊。还公开了微囊化药物制剂及其医疗用途，特别是用于通过包封胰岛素分泌细胞治疗糖尿病。

8. 发明授权

US5871985A Particulate non cross-linked chitosan core matrices for encapsulated cells 失效
标题翻译：用于封装细胞的颗粒非交联壳聚糖核心基质
公开(公告)号：US5871985A
公开(公告)日：1999-02-16
申请号：US294149
申请日：1994-08-22
申请人： Patrick Aebischer , Beth A. Zielinski
发明人： Patrick Aebischer , Beth A. Zielinski
IPC分类号： A61K35/12 , A61L27/20 , A61L27/38 , C12N5/077 , C12N5/0793 , C12N11/10 , C12N11/04 , C12N5/00
CPC分类号： C12N5/0012 , A61L27/20 , A61L27/38 , A61L27/3804 , C12N5/0618 , C12N5/0619 , A61K2035/128 , A61K35/12
摘要： Vehicles containing cells for implanting in the tissue of an individual are prepared having cells dispersed in a particulate, essentially non cross-linked chitosan core matrix that is enclosed within a semipermeable membrane. The cells are entrapped between chitosan particles of the core matrix and there is essentially no interfacial cross-linking between the core matrix and the membrane. The core matrix provides a physical support for viable cells within the vehicle such that the cells are evenly dispersed throughout the core matrix so as to allow their maintenance, growth, proliferation and differentiation. The vehicle can be prepared by mixing viable cells with a solution of chitosan, encapsulating the resultant mixture in a semipermeable membrane and causing the chitosan to precipitate such as by changing the pH to form the core matrix. Alternatively, the chitosan is precipitated to form the core matrix containing cells and then the core matrix is encapsulated in a semipermeable membrane. Cells within the core matrix may be neurosecretory cell lines, .beta.-cell-derived cells lines, fibroblasts, myocytes and glial cells.
摘要翻译：制备含有用于植入个体组织的细胞的载体，其具有分散在颗粒状基本上非交联壳聚糖核心基质中的细胞，所述壳聚糖核心基质被包封在半透膜内。细胞被截留在核心基质的壳聚糖颗粒之间，并且核心基质和膜之间基本上没有界面交联。核心基质为载体内的活细胞提供物理支持，使得细胞均匀分散在整个核心基质中，以使其维持，生长，增殖和分化。载体可以通过将活细胞与壳聚糖溶液混合来制备，将所得混合物包封在半透膜中并使壳聚糖沉淀，例如通过改变pH以形成核心基质。或者，将壳聚糖沉淀形成含核心基质的细胞，然后将核心基质包封在半透膜中。核心基质内的细胞可以是神经分泌细胞系，β-细胞来源的细胞系，成纤维细胞，肌细胞和神经胶质细胞。

9. 发明授权

US5871767A Methods for treatment or prevention of neurodegenerative conditions using immunoisolatory implantable vehicles with a biocompatible jacket and a biocompatible matrix core 失效
标题翻译：使用具有生物相容性护套和生物相容性基质芯的免疫隔离植入式车辆治疗或预防神经变性病症的方法
公开(公告)号：US5871767A
公开(公告)日：1999-02-16
申请号：US449062
申请日：1995-05-24
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 , A61K9/14
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： A method for treatment of a neurodegenerative condition in a patient comprising implanting in the patient at least one immunoisolatory vehicle comprising a corc comprising a volume of at least 1 .mu.l and at least 10.sup.4 living cells which secrete at least one biologically active product, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and an external jacket surrounding the core, the jacket comprising a biocompatible hydrogel or thermoplastic, the jacket being free of cells projecting externally thereof, said jacket having a molecular weight cutoff permitting the passage of the biologically active product from the core through the jacket.
摘要翻译：一种用于治疗患者神经变性病症的方法，包括在患者体内植入至少一种包含至少1μl的体积的corc和至少分泌至少一种生物活性产物的至少104个活细胞的免疫佐剂，所述细胞分散在包含水凝胶或细胞外基质组分的生物相容性基质中，以及围绕芯的外护套，所述护套包括生物相容的水凝胶或热塑性塑料，所述护套不含外部突出的细胞，所述护套具有允许生物活性产物从芯通过夹套。

10. 发明授权

US5843431A Controlling proliferation of cells before and after encapsulation in a bioartificial organ by gene transformation 失效
标题翻译：通过基因转化控制生物人工器官中包封前后细胞的增殖
公开(公告)号：US5843431A
公开(公告)日：1998-12-01
申请号：US432698
申请日：1995-05-09
申请人： Malcolm Schinstine , Molly S. Shoichet , Frank T. Gentile , Joseph P. Hammang , Laura M. Holland , Brian M. Cain , Edward J. Doherty , Shelley R. Winn , Patrick Aebischer
发明人： Malcolm Schinstine , Molly S. Shoichet , Frank T. Gentile , Joseph P. Hammang , Laura M. Holland , Brian M. Cain , Edward J. Doherty , Shelley R. Winn , Patrick Aebischer
IPC分类号： A01K67/027 , A61K48/00 , A61L27/00 , A61L27/18 , A61L27/22 , A61L27/38 , C07K14/82 , C12N5/00 , C12N5/10 , C12N15/09 , C12N15/12 , C12N11/00 , C12N11/10
CPC分类号： A61L27/3839 , A61L27/18 , A61L27/227 , C07K14/82 , C12N5/0012 , C12N5/0068 , A61K48/00 , C12N2510/00 , C12N2510/04 , C12N2533/30 , C12N2533/54 , C12N2533/74
摘要： Methods and compositions are provided for controlling cell distribution within an implantable bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. Cells can be transformed with a proliferation-promoting gene such as the oncogene, SV40, linked to a regulatable promoter such as the Mx1 promoter, the promotor is activated in vitro to express the gene to result in cell proliferation, and the promotor is inactivated before or after insertion of the cells in the bioartificial organ to inhibit expression of the gene to reduce or stop cell proliferation in vivo. The promoter can be reactivated in vivo to again express the gene to result in further cell proliferation. The gene may be a proliferation-suppressing gene such as p53 gene or RB gene, or a differentiation-inducing gene such as high mobility group chromosomal protein 14. Inhibiting gene expression in vitro causes cell proliferation, and inducing gene expression reduces or stops cell proliferation in vivo.
摘要翻译：提供了用于通过将细胞暴露于抑制细胞增殖，促进细胞分化或影响细胞附着于生物人造器官内的生长表面的处理来控制可植入的生物人造器官内的细胞分布的方法和组合物。这样的处理包括（1）遗传操纵细胞，（2）将细胞暴露于增殖抑制化合物或分化诱导化合物，或除去细胞暴露于增殖刺激化合物或分化抑制化合物; 将细胞暴露于照射下，和（3）用细胞外基质分子，影响细胞增殖或粘附的分子，或惰性支架或其组合修饰生物人造器官的生长表面。这些处理可以组合使用。可以用增殖促进基因转化细胞，例如与可调节启动子如Mx1启动子连接的癌基因SV40，启动子在体外被激活以表达基因以导致细胞增殖，并且启动子在或在细胞插入生物人造器官中以抑制基因表达以减少或停止体内细胞增殖。启动子可以在体内再活化以再次表达基因以导致进一步的细胞增殖。该基因可以是增殖抑制基因如p53基因或RB基因，或分化诱导基因如高迁移率组染色体蛋白14.体外抑制基因表达引起细胞增殖，诱导基因表达降低或停止细胞增殖体内。

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