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公开(公告)号：US5704908A
公开(公告)日：1998-01-06
申请号：US729007
申请日：1996-10-10
摘要： An electroporation apparatus for introducing molecules into cells at a selected location within a cavity in the body of a patient includes an elongated catheter having a proximal end and a distal end and a guide wire extending from the proximal end to the distal end, an inflatable balloon carried by the distal end, the balloon having an inner inflatable bladder and an outer perforated bladder defining a chamber between the two bladders, a first electrode on an outer surface of the outer perforated bladder, a second electrode spaced from the first electrode, a remote electrode, a lumen for delivering a predetermined quantity of a fluid medium carrying preselected molecules into the chamber to be infused into the body cavity at the predetermined location; and a source of power for applying a voltage pulse between selected pairs of the electrodes for transport of the molecules by iontophoresis and/or repeatedly generating electric fields of a predetermined amplitude and duration inducing the walls of a plurality of cells at the predetermined location to be transiently permeable to enable the molecules to enter the cells.
摘要翻译： 用于在患者体内的空腔内的选定位置处将分子引入细胞的电穿孔装置包括具有近端和远端的细长导管和从近端延伸到远端的导丝，可膨胀气囊 所述气囊具有内部可充气气囊和在所述两个气囊之间限定室的外部穿孔气囊，所述外部穿孔气囊的外表面上的第一电极，与所述第一电极间隔开的第二电极，远端 电极，用于将预定量的携带预选分子的流体介质输送到所述腔室中以在预定位置输注到体腔内腔; 以及用于在所选择的电极对之间施加电压脉冲的电源，用于通过离子电渗传输分子和/或重复产生预定幅度和持续时间的电场，从而诱导预定位置处的多个电池的壁为 瞬时渗透以使分子进入细胞。
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42.发明授权Transsurface drug delivery by electrofusion of microbubbles to the tissue surface 失效通过将微泡电融合到组织表面的经表面药物递送
公开(公告)号：US5462520A
公开(公告)日：1995-10-31
申请号：US219970
申请日：1994-03-30
申请人： Gunter A. Hofmann
发明人： Gunter A. Hofmann
CPC分类号： A61N1/303 , A61N1/327 , A61M2037/0007 , Y10T428/2984
摘要： A method of transtissue molecular delivery comprises encapsulating molecules to be delivered in a microbubble carrier, contacting a selected area of a tissue surface with a solution of the encapsulated molecules, and applying an electric field of sufficient amplitude to induce electrofusion between the tissue and the membrane of the microbubble.
摘要翻译： 转运分子递送的方法包括将要在微泡载体中递送的分子包封，将组织表面的选定区域与包封分子的溶液接触，并施加足够幅度的电场以诱导组织和膜之间的电融合 的微泡。
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43.发明授权
公开(公告)号：US5318514A
公开(公告)日：1994-06-07
申请号：US931061
申请日：1992-08-17
申请人： Gunter A. Hofmann
发明人： Gunter A. Hofmann
CPC分类号： A61N1/327 , A61N1/303 , A61M2037/0007
摘要： An apparatus for implanting macromolecules such as genes, DNA or pharmaceuticals into a preselected surface tissue region of of a patient. An applicator having a plurality of electrodes is provided for contacting a surface tissue region of a patient. A mechanism associated with the applicator delivers a predetermined quantity of a fluid medium carrying the preselected macromolecules. A signal generator is provided for generating a predetermined electric signal. The electrodes of the applicator are connected to the signal generator for applying an electric field in the surface tissue region. The field has a predetermined strength and duration in order to make the walls of a plurality of cells in the surface tissue region transiently permeable to permit the macromolecules to enter said preselected cells without damaging said cells. This enhances the uptake of macromolecules and thus enhances the therapeutic effect achieved.
摘要翻译： 用于将大分子如基因，DNA或药物植入患者的预选表面组织区域中的装置。 提供具有多个电极的施加器，用于接触患者的表面组织区域。 与施用器相关联的机构输送预定量的携带预选大分子的流体介质。 提供信号发生器用于产生预定的电信号。 施加器的电极连接到信号发生器，用于在表面组织区域中施加电场。 该场具有预定的强度和持续时间，以使得表面组织区域中的多个细胞的壁瞬时渗透以允许大分子进入所述预选细胞而不损坏所述细胞。 这增强了大分子的吸收，从而增强了所获得的治疗效果。
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44.发明授权Electroporation method and apparatus for insertion of drugs and genes into endothelial cells 失效用于将药物和基因插入内皮细胞的电穿孔方法和装置
公开(公告)号：US5304120A
公开(公告)日：1994-04-19
申请号：US907322
申请日：1992-07-01
摘要： A catheter device is inserted into a selected blood vessel of a patient and advanced to a preselected location within the blood vessel where the endothelial cells on the inner wall of the vessel are to be treated. Once in place, the catheter device is expanded so that a plurality of axially extending, circumferentially spaced electrodes carried thereby are in contact with the inner wall of the blood vessel. A fluid medium is then infused into the blood vessel adjacent the electrodes via a conventional pump. A power pack connected to the electrodes is energized to apply a predetermined electric signal to the electrodes. This subjects the endothelial cells to electric fields of predetermined amplitude and duration in order to make the walls of the endothelial cells transiently permeable to permit therapeutic genes or drugs carried by the fluid medium to enter the endothelial cells without killing them.
摘要翻译： 将导管装置插入到患者的所选择的血管中并且前进到血管内预先选定的位置，其中血管内壁上的内皮细胞将被处理。 一旦就位，导管装置被扩张，使得由其携带的多个轴向延伸的周向隔开的电极与血管的内壁接触。 然后通过常规泵将流体介质输入到与电极相邻的血管中。 连接到电极的电源组通电以向电极施加预定的电信号。 这将使内皮细胞受到预定幅度和持续时间的电场，以使内皮细胞的壁瞬时渗透以允许治疗基因或由流体介质携带的药物进入内皮细胞而不杀死它们。
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公开(公告)号：US07412284B2
公开(公告)日：2008-08-12
申请号：US09900601
申请日：2001-07-05
申请人： Gunter A. Hofmann
发明人： Gunter A. Hofmann
CPC分类号： A61N1/327 , A61N1/0502 , A61N1/325 , C12M35/02
摘要： A device for in vivo electroporation therapy comprising an electrode applicator with at least two pairs of electrodes arranged relative to one another to form an array and a power supply. The device is used to generate an electric field in a biological sample and effect introduction of selected molecules into cells of the sample.
摘要翻译： 一种用于体内电穿孔治疗的装置，包括具有相对于彼此布置的至少两对电极的电极施加器，以形成阵列和电源。 该装置用于在生物样品中产生电场并且将所选择的分子引入样品的细胞中。
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公开(公告)号：US06865416B2
公开(公告)日：2005-03-08
申请号：US09969367
申请日：2001-10-01
CPC分类号： A61N1/327 , A61N1/325 , Y10S977/883 , Y10S977/904 , Y10S977/905
摘要： The invention provides methods for inducing or increasing the vasodilation of a vessel. The invention further provides methods for inducing or increasing the flow of fluid through a vessel. An electrical impulse is applied to the vessel in order to induce or increase vessel vasodilation or to induce or increase the flow of fluid through the vessel. In a particular embodiment, a novel double-balloon catheter system incorporating electroporation technology has been designed and is used to apply the electrical impulse endoluminally.
摘要翻译： 本发明提供诱导或增加血管的血管舒张的方法。 本发明还提供了用于诱导或增加通过容器的流体流动的方法。 为了诱导或增加血管血管舒张或诱导或增加通过血管的流体流动，向血管施加电脉冲。 在一个具体的实施方案中，已经设计了一种包含电穿孔技术的新型双气囊导管系统，并且被用于内腔内施加电脉冲。
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公开(公告)号：US06347247B1
公开(公告)日：2002-02-12
申请号：US09307216
申请日：1999-05-07
IPC分类号： A61N100
CPC分类号： A61N1/327 , A61N1/325 , Y10S977/883 , Y10S977/904 , Y10S977/905
摘要： The invention provides methods for inducing or increasing the vasodilation of a vessel. The invention further provides methods for inducing or increasing the flow of fluid through a vessel. An electrical impulse is applied to the vessel in order to induce or increase vessel vasodilation or to induce or increase the flow of fluid through the vessel. In a particular embodiment, a novel double-balloon catheter system incorporating electroporation technology has been designed and is used to apply the electrical impulse endoluminally.
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48.发明授权公开(公告)号：US06192270B1
公开(公告)日：2001-02-20
申请号：US09134245
申请日：1998-08-14
IPC分类号： A61N130
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 and a method of trans-surface molecular delivery, including 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 first electrode disposed on at least a portion of the distal surface and extending through at least a portion of the plurality of through holes and onto at least a portion of the proximal surface, a second electrode disposed on at least a portion of the proximal surface and in closely spaced relation with the first electrode for engaging a tissue surface through which to apply an electric field, and an insulating barrier that is disposed on at least a portion of the proximal surface of the carrier between the first electrode and the second electrode.
摘要翻译： 一种用于反式表面分子传递的装置和方法的电极组件，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，第一电极 设置在所述远端表面的至少一部分上并且延伸穿过所述多个通孔的至少一部分并且延伸到所述近端表面的至少一部分上，第二电极，设置在所述近端表面的至少一部分上并且紧密地 与用于接合施加电场的组织表面的第一电极间隔开的关系;以及设置在第一电极和第二电极之间的载体近端表面的至少一部分上的绝缘屏障。
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49.发明授权Minimally invasive apparatus and method to electroporate drugs and genes into tissue 有权将药物和基因电穿孔进入组织的微创装置和方法公开(公告)号：US06181964B2
公开(公告)日：2001-01-30
申请号：US09189360
申请日：1998-11-09
申请人： Gunter A. Hofmann , Sukhendu B. Dev , Steven C. Dimmer , Jeffrey I. Levatter , Gurvinder S. Nanda
发明人： Gunter A. Hofmann , Sukhendu B. Dev , Steven C. Dimmer , Jeffrey I. Levatter , Gurvinder S. Nanda
IPC分类号： A61N130
CPC分类号： A61N1/327 , A61N1/0502 , A61N1/325
摘要： A method and apparatus for in vivo electroporation therapy. Using electroporation therapy (EPT) as described in the invention, tumors treated by a combination of electroporation using the apparatus of the invention and a chemotherapeutic agent caused regression of tumors in vivo. In one embodiment, the invention provides a method of EPT utilizing low voltage and long pulse length for inducing cell death. One embodiment of the invention includes a system for clinical electroporation that includes a needle array electrode having a “keying” element that determines the set point of the therapy voltage pulse and/or selectable array switching patterns. A number of electrode applicator designs permit access to and treatment of a variety of tissue sites. Another embodiment provides a laparoscopic needle applicator that is preferably combined with an endoscope for minimally invasive EPT.
摘要翻译： 一种用于体内电穿孔治疗的方法和装置。 使用本发明所述的电穿孔治疗（EPT），通过使用本发明的装置的电穿孔和化学治疗剂的组合治疗的肿瘤引起体内肿瘤消退。 在一个实施方案中，本发明提供了一种利用低电压和长脉冲长度诱导细胞死亡的EPT的方法。 本发明的一个实施例包括用于临床电穿孔的系统，其包括具有确定治疗电压脉冲和/或可选阵列切换模式的设定点的“键控”元件的针阵列电极。 许多电极施加器设计允许访问和处理各种组织部位。 另一实施例提供一种腹腔镜针施加器，其优选地与用于微创EPT的内窥镜组合。
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公开(公告)号：US6132419A
公开(公告)日：2000-10-17
申请号：US328895
申请日：1994-10-25
申请人： Gunter A. Hofmann
发明人： Gunter A. Hofmann
摘要： A method and apparatus are provided for introducing molecules such as genes and pharmaceutical compounds into living blood cells of a patient for therapeutic purposes. A device is placed into contact with 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 applied 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 an induction coil that is placed into contact with the body over a 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。 将装置放置成与患者的身体接触，以在所选择的血管内的预选位置处产生电场。 将预先选择的分子注入选定的血管。 同时，向所施加的装置施加电信号，以将在所选择的血管内流动的一定数量的血液重复地经过预选位置到预定的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。 该装置可以包括放置在血管上与身体接触的感应线圈，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。
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