公开(公告)号：US10369359B2

公开(公告)日：2019-08-06

申请号：US11704591

申请日：2007-02-09

申请人： Rune Kjeken ,  Iacob Mathiesen ,  Elisabeth Torunn Tjelle ,  George McHugh

发明人： Rune Kjeken ,  Iacob Mathiesen ,  Elisabeth Torunn Tjelle ,  George McHugh

IPC分类号： A61N1/32 ,  A61N1/30

摘要： Described is a device and method for administration of molecules to tissue in vivo for various medical applications, the device comprising a single hypodermic injection needle and at least two spaced elongate electrodes which provide for the ability, when the needle is inserted into tissue, such as skin or muscle, to pulse tissue with a non-uniform electric field sufficient to cause reversible poration of cells lying along or in close proximity to the track made by the needle upon its insertion into said tissue.

公开(公告)号：US07395110B2

公开(公告)日：2008-07-01

申请号：US10783164

申请日：2004-02-20

申请人： Günter A. Hofmann ,  Dietmar P. Rabussay ,  Zei Zhang

发明人： Günter A. Hofmann ,  Dietmar P. Rabussay ,  Zei Zhang

IPC分类号： A61N1/30

CPC分类号： A61N1/0424 ,  A61N1/042 ,  A61N1/0436 ,  A61N1/044 ,  A61N1/30 ,  A61N1/325

摘要： An electrode assembly for an apparatus for trans-surface molecular includes a non-conductive carrier having a proximal surface, a distal surface, and a plurality of through holes from the proximal surface to the distal surface, a plurality of first electrodes disposed on the proximal surface, a first conductor disposed on at least a first portion of the distal surface and extending through at least a first portion of the plurality of through holes and connected to the first electrodes on the proximal surface, a plurality of second electrodes disposed on the proximal surface, and a second conductor disposed on at least a second portion of the distal surface and extending through at least a second portion of the plurality of through holes and connected to the second electrodes on the proximal surface, wherein the first electrodes and the second electrodes are configured and disposed in closely spaced relation on the proximal surface for engaging the tissue surface and applying an electric field.

摘要翻译： 用于反式表面分子的装置的电极组件包括具有近端表面，远端表面和从近端表面到远端表面的多个通孔的非导电载体，多个第一电极，其设置在近端 表面，设置在所述远端表面的至少第一部分上并延伸穿过所述多个通孔的至少第一部分并且连接到所述近端表面上的所述第一电极的第一导体，设置在所述近端的多个第二电极 表面和第二导体，其设置在远端表面的至少第二部分上并且延伸穿过多个通孔的至少第二部分并且连接到近端表面上的第二电极，其中第一电极和第二电极 在近侧表面上以紧密间隔的关系配置和设置，用于接合组织表面并施加电极 c字段。

公开(公告)号：US20060115888A1

公开(公告)日：2006-06-01

申请号：US10537203

申请日：2003-12-03

申请人： Andre Gamelin ,  Daniel Holt ,  Christian Andre

发明人： Andre Gamelin ,  Daniel Holt ,  Christian Andre

IPC分类号： C12M1/42

CPC分类号： C12M35/02 ,  C12M23/12 ,  C12M41/48

摘要： Described are electroporation plates (2) that comprise a plurality of energizable electroporation wells (4) or chambers arrayed in a solid substrate, wherein at least two of the wells (4) in the plate (2) can be independently energized. Each well (4) contains at least two electroporation electrodes (12, 14) disposed therein, and serves as the vessel in which an individual electroporation reaction can be conducted. Also, described are electroporation systems that use electroporation plates (2) according to the invention, as well as methods of using such electroporation plates (2) and systems, for example, to optimize electroporation conditions.

摘要翻译： 描述的是电穿孔板（2），其包括排列在固体衬底中的多个可激发的电穿孔孔（4）或腔室，其中板（2）中的孔（4）中的至少两个可以独立地通电。 每个孔（4）包含至少两个设置在其中的电穿孔电极（12,14），并且用作能够进行个别电穿孔反应的容器。 还描述了使用根据本发明的电穿孔板（2）的电穿孔系统，以及使用这种电穿孔板（2）和系统的方法，例如优化电穿孔条件。

公开(公告)号：US5993434A

公开(公告)日：1999-11-30

申请号：US537265

申请日：1995-09-29

申请人： Sukhendu B. Dev ,  Gunter A. Hofmann

发明人： Sukhendu B. Dev ,  Gunter A. Hofmann

IPC分类号： A61N1/32 ,  A61M31/00

CPC分类号： A61N1/327 ,  A61N1/325 ,  C12M35/02

摘要： A method for in vivo electrotherapy, or electroporation-mediated therapy, using a needle array apparatus is provided. Treatment of tumors with a combination of electroporation using the apparatus of the invention, and a chemotherapeutic agent, caused regression of tumors in vivo.

公开(公告)号：US5944710A

公开(公告)日：1999-08-31

申请号：US668725

申请日：1996-06-24

申请人： Sukhendu B. Dev ,  Nagendu B. Dev ,  Gunter A. Hofmann

发明人： Sukhendu B. Dev ,  Nagendu B. Dev ,  Gunter A. Hofmann

IPC分类号： B82B1/00 ,  A61F2/958 ,  A61N1/30 ,  A61N1/32 ,  A61M31/00

CPC分类号： A61N1/327 ,  A61N1/325 ,  A61N1/306 ,  Y10S977/906

摘要： A method for sustained intravascular delivery via electroporation is provided. The method is useful for delivery of therapeutic compositions such as antithrombotic and anticoagulant agents. The invention also provides a catheter apparatus for introducing a composition into at least one cell in a vessel in a subject.

公开(公告)号：US5869326A

公开(公告)日：1999-02-09

申请号：US709615

申请日：1996-09-09

申请人： Gunter A. Hofmann

发明人： Gunter A. Hofmann

IPC分类号： C12M1/00 ,  A61M37/00 ,  C12M1/42 ,  C12M3/00 ,  C12N15/87 ,  H03K3/45 ,  H03K3/57 ,  C12M3/02 ,  C12M3/04

CPC分类号： H03K3/57 ,  C12M35/02 ,  C12N15/87

摘要： An electroporation method and apparatus generating and applying an electric field according to a user-specified pulsing scheme. Advantageously, one such pulse includes a low voltage pulse of a first duration, immediately followed by a high voltage of a second duration, immediately followed by a low voltage of a third duration. The low voltage electroporation field accumulates molecules at the surface of a cell, the appropriately high voltage field creates an opening in the cell, and the final low voltage field moves the molecule into the cell. The molecules may be DNA, portions of DNA, chemical agents, the receiving cells may be eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, sperm, or other suitable cells. The molecules are placed in close proximity to the cells, either in the interstitial space in tissue surrounding the cells or in a fluid medium containing the cells.

公开(公告)号：US5507724A

公开(公告)日：1996-04-16

申请号：US183963

申请日：1994-01-21

申请人： Gunter A. Hofmann ,  Lois J. Crandell

发明人： Gunter A. Hofmann ,  Lois J. Crandell

IPC分类号： C12N15/09 ,  A61M29/00 ,  A61M31/00 ,  A61N1/30 ,  A61N1/32

CPC分类号： A61M29/02 ,  A61M31/00 ,  A61N1/306 ,  A61N1/325 ,  A61N1/327 ,  C12M35/02

摘要： A catheter device having a plurality of axially extending, circumferentially spaced electrodes carried thereby, infusion means for infusion of fluid medium for carrying genes and drugs, and expandable sealing means at each end of the electrodes for sealing off and confining the therapeutic medium to the area to be treated is inserted into a selected blood vessel of a patient and advanced to a preselected location within the blood vessel where cells on or near the wall of the vessel are to be treated. Once in place, the catheter device is expanded so that the plurality of axially extending, circumferentially spaced electrodes carried thereby are in contact with the inner wall of the blood vessel and seals at each end of the electrodes expand and seal the catheter device in the preselected location. A quantity of therapeutic genes or drugs is infused into the area of the electrodes via a tube and a conventional pump. A power pack connected to the electrodes is energized subjecting the cells to electric fields of predetermined amplitude and duration making the walls of the cells transiently permeable to enabling therapeutic genes or drugs carried by the fluid medium to enter the cells without killing them.

摘要翻译： 导管装置，其具有多个沿轴向延伸的周向隔开的电极，由此输送用于输送用于携带基因和药物的流体介质的输注装置，以及用于密封和限制治疗介质至该区域的电极的每个端部处的可膨胀密封装置 被处理的细胞被插入到患者的选定的血管中并且前进到血管内的预定位置，其中待处理血管壁上或其附近的细胞。 一旦就位，导管装置被扩张，使得由其携带的多个沿轴向延伸的周向间隔开的电极与血管的内壁接触，并且在电极的每个端部处的密封件将预先选定的导管装置膨胀和密封 位置。 一些治疗基因或药物通过管和常规泵注入电极区域。 连接到电极的电源组通电使细胞进入具有预定振幅和持续时间的电场，使得细胞壁瞬时渗透，使得流体介质携带的治疗基因或药物进入细胞而不杀死细胞。

公开(公告)号：US5501662A

公开(公告)日：1996-03-26

申请号：US304584

申请日：1994-09-12

申请人： Gunter A. Hofmann

发明人： Gunter A. Hofmann

IPC分类号： A61N1/32 ,  A61N1/30

CPC分类号： A61N1/327 ,  A61N1/325

摘要： A method and apparatus are provided for introducing molecules such as genes and pharmacological compounds into living blood cells of a patient for therapeutic purposes. A device is implanted into the body of the patient for generating an electric field at a preselected location within a selected blood vessel. Preselected molecules are infused into the selected blood vessel. Simultaneously an electric signal is applied to the implanted device to repeatedly subject a quantity of blood flowing within the selected blood vessel past the preselected location to electric fields of a predetermined amplitude and duration. The parameters of the electric fields are precisely controlled in order to make the walls of preselected cells in the blood transiently permeable to permit the molecules to enter said preselected cells without killing said cells. The device can include either a pair of electrodes implanted in the blood vessel, or alternatively, an induction coil that surrounds the blood vessel. The electric signal is supplied by a power pack and the preselected molecules are infused with a supply pump.

摘要翻译： 为了治疗目的，提供了一种方法和装置，用于将诸如基因和药物化合物的分子引入患者的活血细胞。 将装置植入患者体内，以在选定的血管内的预选位置产生电场。 将预先选择的分子注入选定的血管。 同时，将电信号施加到植入装置，以将选定血管内流动的血液数量反复超过预选位置至预定幅度和持续时间的电场。 精确地控制电场的参数，以使血液中预选细胞的壁瞬时渗透以允许分子进入所述预选细胞而不杀死所述细胞。 该装置可以包括植入血管中的一对电极，或者包括围绕血管的感应线圈。 电信号由电源组提供，并且预选的分子注入供应泵。

公开(公告)号：US20080215032A1

公开(公告)日：2008-09-04

申请号：US10516757

申请日：2003-03-25

申请人： Dietmar P. Rabussay

发明人： Dietmar P. Rabussay

IPC分类号： A61N1/30 ,  A61M31/00 ,  A61N1/32 ,  A61N1/05 ,  A61K31/7088

CPC分类号： C12N15/87 ,  A61K48/0083

摘要： Methods are provided for introducing a polynucleotide into healthy tissue and generating a pulsed electric field in the tissue via invasive electrodes, resulting in enhanced delivery of the polynucleotide into cells of the tissue, while minimizing local side effects to the electroporated tissue and systemic side effects to the electroporated organism due to metal contaminants released from said electrodes. In one embodiment, the invention methods Use electrodes of gold, gold alloys, or other metal that minimize the introduction of toxic amounts of the metal into electroporated tissue. In other embodiments, the invention methods are utilized for the gene therapy by administering DNA to cells of suitable target tissue, and for the induction of an immune response by administration of a DNA vaccine.

摘要翻译： 提供了用于将多核苷酸引入健康组织中并通过侵入电极在组织中产生脉冲电场的方法，导致多核苷酸进入组织细胞的增强递送，同时最小化对电穿孔组织的局部副作用和全身副作用 由于从所述电极释放的金属污染物导致的电穿孔生物体。 在一个实施方案中，本发明方法使用金，金合金或其它金属的电极，其将毒性量的金属引入电穿孔组织中最小化。 在其它实施方案中，本发明方法用于通过向合适的靶组织的细胞施用DNA以及通过施用DNA疫苗来诱导免疫应答来进行基因治疗。

公开(公告)号：US20080058706A1

公开(公告)日：2008-03-06

申请号：US11784892

申请日：2007-04-10

申请人： Lei Zhang ,  Andre Gamelin ,  Dietmar Rabussay

发明人： Lei Zhang ,  Andre Gamelin ,  Dietmar Rabussay

IPC分类号： A61N1/30

CPC分类号： A61N1/327 ,  A61N1/0412

摘要： The invention comprises a modular electroporation device for use in clinical settings. The device includes components which may be varied or adapted for application of electroporation-based delivery of therapeutic agents to cells of a subject in a variety of electroporation formats such as intratissue electroporation or transsurface electroporation. The device components include a hand-manipulable handle with activation switch and a disposable head comprising electrodes, injection port, electrode directional and depth guide, and a slideably engaged electrode safety shield.

摘要翻译： 本发明包括用于临床设置的模块化电穿孔装置。 该装置包括可以变化或适于以多种电穿孔形式（例如组织间电穿孔或经表面电穿孔）将治疗剂施用于受试者细胞的电穿孔为基础的组分。 装置部件包括具有致动开关的可手动手柄和包括电极，注射端口，电极定向和深度引导件以及可滑动接合的电极安全屏蔽件的一次性头部。