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1. 发明授权

US07171264B1 Intradermal delivery of active agents by needle-free injection and electroporation 有权
标题翻译：通过无针注射和电穿孔活性剂的皮内递送
公开(公告)号：US07171264B1
公开(公告)日：2007-01-30
申请号：US10339708
申请日：2003-01-08
申请人： Gunter A. Hofmann , Dietmar P. Rabussay , Lei Zhang
发明人： Gunter A. Hofmann , Dietmar P. Rabussay , Lei Zhang
IPC分类号： A61N1/30
CPC分类号： A61N1/0424 , A61N1/0428 , A61N1/325
摘要： Methods are proved for introducing a biologically active agent into cells of a subject by introducing the agent in a form suitable for electrotransport into a region of tissue of the subject using one or more needle-free injectors, and applying a pulsed electric field to the region of tissue, thereby causing electroporation of the region of tissue. The combination of needle-free injection and electroporation is sufficient to introduce the agent into cells in skin, muscle or mucosa. For example, the region of tissue can be contacted with two oppositely charged injectors, one acting as the donor electrode and one acting as the counter electrode, or a single injector and one or more electrodes can be used. In addition, needle-free injection may be used in combination with suitable non-invasive electrode configurations. The active agents delivered into cells using the invention method can be small molecules, polynucleotides, polypeptides, and the like.
摘要翻译：证明通过使用一种或多种无针注射器将适合于电转移到受试者组织区域的形式引入生物活性剂来引入生物活性剂的方法，以及向该区域施加脉冲电场的组织，从而引起组织区域的电穿孔。无针注射和电穿孔的组合足以将药剂引入皮肤，肌肉或粘膜中的细胞中。例如，组织区域可以与两个相反电荷的注射器接触，一个充当施主电极，另一个充当对电极，或者可以使用单个注射器和一个或多个电极。此外，无针注射可以与合适的非侵入性电极结构组合使用。使用本发明方法递送到细胞中的活性剂可以是小分子，多核苷酸，多肽等。

2. 发明授权

US06697669B2 Skin and muscle-targeted gene therapy by pulsed electrical field 有权
公开(公告)号：US06697669B2
公开(公告)日：2004-02-24
申请号：US09352809
申请日：1999-07-13
申请人： Nagendu B. Dev , Gunter A. Hofmann , Edward Nolan , Dietmar P. Rabussay , Arnt Tonnessen , Georg Widera , Lei Zhang
发明人： Nagendu B. Dev , Gunter A. Hofmann , Edward Nolan , Dietmar P. Rabussay , Arnt Tonnessen , Georg Widera , Lei Zhang
IPC分类号： A61N130
CPC分类号： A61N1/327 , A61N1/0424 , A61N1/0452 , A61N1/306 , A61N1/325
摘要： The present invention describes an in vivo method, using pulsed electric field to deliver therapeutic agents into cells of the skin and muscle for local and systemic treatments. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.

3. 发明授权

US06302874B1 Method and apparatus for electrically assisted topical delivery of agents for cosmetic applications 失效
标题翻译：用于化妆品应用的药剂的电辅助局部递送的方法和装置
公开(公告)号：US06302874B1
公开(公告)日：2001-10-16
申请号：US09352818
申请日：1999-07-13
申请人： Lei Zhang , Gunter A. Hofmann
发明人： Lei Zhang , Gunter A. Hofmann
IPC分类号： A61M3100
CPC分类号： A61N1/327 , A61N1/0424 , A61N1/0428 , A61N1/0436 , A61N1/0448 , A61N1/0468 , A61N1/325
摘要： The present invention is based on the development of a method for cosmetic delivery of L-ascorbic acid-containing compositions to the layer of the skin wherein collagen formation takes place to enhance production of collagen and thereby combat some of the effects of aging and oxy-radical damage on skin. Sufficient electric pulses applied to a region of skin surface temporarily create new pathways through the lipid skin barrier, thereby delivering an L-ascorbic acid-containing composition through the lipid skin barrier and enhancing production of collagen in the region of the skin so treated. A handheld electrical pulser apparatus, optionally table-top adaptable, and methods of use for cosmetic treatment of degenerative skin conditions are provided by the invention.
摘要翻译：本发明基于开发用于将L-抗坏血酸的组合物美容递送到皮肤层的方法，其中发生胶原蛋白形成以增强胶原蛋白的产生，从而抵抗老化和氧化 - 对皮肤有根本的伤害。施加到皮肤表面区域的足够的电脉冲暂时产生通过脂质皮肤屏障的新途径，从而通过脂质皮肤屏障输送含L-抗坏血酸的组合物，并增强如此治疗的皮肤区域中的胶原蛋白的产生。本发明提供了一种手持式电脉冲发生器装置，任选桌面适应性，以及用于美容治疗退行性皮肤病症的方法。

4. 发明授权

US06947791B2 Method and apparatus for electrically assisted topical delivery of agents for cosmetic applications 失效
标题翻译：用于化妆品应用的药剂的电辅助局部递送的方法和装置
公开(公告)号：US06947791B2
公开(公告)日：2005-09-20
申请号：US09966390
申请日：2001-09-27
申请人： Lei Zhang , Gunter A. Hofmann
发明人： Lei Zhang , Gunter A. Hofmann
IPC分类号： A61N1/30 , A61N1/32
CPC分类号： A61N1/327 , A61N1/0424 , A61N1/0428 , A61N1/0436 , A61N1/0448 , A61N1/0468 , A61N1/325
摘要： The present invention is based on the development of a method for cosmetic delivery of L-ascorbic acid-containing compositions to the layer of the skin wherein collagen formation takes place to enhance production of collagen and thereby combat some of the effects of aging and oxy-radical damage on skin. Sufficient electric pulses applied to a region of skin surface temporarily create new pathways through the lipid skin barrier, thereby delivering an L-ascorbic acid-containing composition through the lipid skin barrier and enhancing production of collagen in the region of the skin so treated. A handheld electrical pulser apparatus, optionally table-top adaptable, and methods of use for cosmetic treatment of degenerative skin conditions are provided by the invention.
摘要翻译：本发明基于开发用于将L-抗坏血酸的组合物美容递送到皮肤层的方法，其中发生胶原蛋白形成以增强胶原蛋白的产生，从而抵抗老化和氧化 - 对皮肤有根本的伤害。施加到皮肤表面区域的足够的电脉冲暂时产生通过脂质皮肤屏障的新途径，从而通过脂质皮肤屏障输送含L-抗坏血酸的组合物，并增强如此治疗的皮肤区域中的胶原蛋白的产生。本发明提供了一种手持式电脉冲发生器装置，任选桌面适应性，以及用于美容治疗退行性皮肤病症的方法。

5. 发明授权

US06654636B1 Skin and muscle-targeted gene therapy by pulsed electrical field 有权
标题翻译：通过脉冲电场进行皮肤和肌肉靶向基因治疗
公开(公告)号：US06654636B1
公开(公告)日：2003-11-25
申请号：US09625825
申请日：2000-07-26
申请人： Nagendu B. Dev , Gunter A. Hofmann , Edward Nolan , Dietmar P. Rabussay , Arnt Tonnessen , Georg Widera , Lei Zhang
发明人： Nagendu B. Dev , Gunter A. Hofmann , Edward Nolan , Dietmar P. Rabussay , Arnt Tonnessen , Georg Widera , Lei Zhang
IPC分类号： A61N130
CPC分类号： A61N1/327 , A61N1/0424 , A61N1/0452 , A61N1/306 , A61N1/325
摘要： The present invention describes an in vivo method, using pulsed electric field to deliver therapeutic agents into cells of the skin and muscle for local and systemic treatments. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.
摘要翻译：本发明描述了体内方法，使用脉冲电场将治疗剂递送到皮肤和肌肉的细胞中用于局部和全身治疗。特别地，治疗剂包括裸体或配制的核酸，多肽和化学治疗剂。

6. 发明授权

US06520950B1 Method of electroporation-enhanced delivery of active agents 有权
标题翻译：电穿孔增强活性剂递送方法
公开(公告)号：US06520950B1
公开(公告)日：2003-02-18
申请号：US09567404
申请日：2000-05-08
申请人： Gunter A. Hofmann , Dietmar P. Rabussay , Lei Zhang
发明人： Gunter A. Hofmann , Dietmar P. Rabussay , Lei Zhang
IPC分类号： A61M2500
CPC分类号： A61N1/327 , A61N1/0412 , A61N1/0424 , A61N1/0428 , A61N1/0476 , A61N1/30 , A61N1/306 , A61N1/325 , Y10S977/906
摘要： Methods are provided for introducing a biologically active agent into cells of a subject by injecting the agent with a needle-free injector and applying a pulsed electric field to the region of tissue to cause electrotransport of the agent into cells of the tissue. Preferably the agent is either ionized to some degree or contained in an ionized medium for electrotransport. The needle-free injector can serve as an electrode by which the pulsed electric field is applied to the region of tissue. The active agents delivered into cells by this method include small molecules, polynucleotides, polypeptides, and the like. Polynucleotides introduced into cells using this method can be used to accomplish gene therapy or to modulate expression of an endogenous gene.
摘要翻译：提供了通过用无针注射器注入药剂并将组织上的脉冲电场施加到组织区域以引起药物转移到组织细胞中而将生物活性剂引入受试者细胞的方法。优选地，试剂在一定程度上被电离或包含在用于电转运的电离介质中。无针注射器可用作电极，通过该电极将脉冲电场施加到组织区域。通过该方法递送到细胞中的活性剂包括小分子，多核苷酸，多肽等。使用该方法引入细胞的多核苷酸可用于完成基因治疗或调节内源基因的表达。

7. 发明授权

US06266560B1 Electrically assisted transdermal method and apparatus for the treatment of erectile dysfunction 失效
标题翻译：用于治疗勃起功能障碍的电辅助透皮方法和仪器
公开(公告)号：US06266560B1
公开(公告)日：2001-07-24
申请号：US09336400
申请日：1999-06-18
申请人： Lei Zhang , Gunter A. Hofmann , Dietmar Rabussay
发明人： Lei Zhang , Gunter A. Hofmann , Dietmar Rabussay
IPC分类号： A61N144
CPC分类号： A61N1/36007 , Y10S977/906
摘要： A non-invasive method is provided for treating erectile dysfunction using electroporation enhanced with delivery of a vasoactive or androgenic composition applied to the penis which affords an alternative treatment for patients afflicted with erectile dysfunction (ED). Sufficient electric pulses temporarily create new pathways in the penile skin thereby driving a composition, such as a vasoactive or androgenic medication, into the corporal cavernosum.
摘要翻译：提供一种非侵入性方法，用于使用通过递送施用于阴茎的血管活性或雄激素成分增强的电穿孔来治疗勃起功能障碍，其为患有勃起功能障碍（ED）的患者提供替代治疗。足够的电脉冲暂时在阴茎皮肤中产生新的途径，从而将组合物（例如血管活性或雄激素药物）驱动到体外海绵体中。

8. 发明授权

US5688233A Electronincorporation enhanced transdermal delivery of molecules 失效
标题翻译：电子增强分子的透皮递送
公开(公告)号：US5688233A
公开(公告)日：1997-11-18
申请号：US552200
申请日：1995-11-02
申请人： Gunter A. Hofmann , Lei Zhang
发明人： Gunter A. Hofmann , Lei Zhang
IPC分类号： A61N1/30 , A61N1/32 , A61K38/00
CPC分类号： A61N1/303 , A61N1/0424 , A61N1/325 , A61M2037/0007 , A61N1/044 , A61N1/306
摘要： A method of transdermal molecular delivery comprising molecules to be delivered mixed with particles, contacting a selected area of a skin surface with the particles and molecules, applying a pulsed electric field of sufficient amplitude and duration to induce dielectric breakdown of the stratum corneum, and applying a pressure to the molecules to force transport of the molecules through the pores in the stratum corneum into the underlying skin.
摘要翻译：一种经皮分子传递的方法，其包括与颗粒混合的分子，将皮肤表面的选定区域与颗粒和分子接触，施加足够幅度和持续时间的脉冲电场以诱导角质层的电击穿，并施加分子的压力迫使分子通过角质层中的孔进入下面的皮肤。

9. 发明授权

US06746441B1 Flow-through electroporation system for ex vivo gene therapy 失效
标题翻译：用于离体基因治疗的流通电穿孔系统
公开(公告)号：US06746441B1
公开(公告)日：2004-06-08
申请号：US09470567
申请日：1999-12-22
申请人： Gunter A. Hofmann , Dietmar Rabussay
发明人： Gunter A. Hofmann , Dietmar Rabussay
IPC分类号： A61M3100
CPC分类号： A61N1/327 , A61N1/306 , A61N1/325 , C12M35/02
摘要： A method and apparatus for introducing a preselected molecule into a living cell by contacting the cell with the preselected molecule and applying a multiple series of electrical pulses to the cell. The method can be utilized ex vivo. The multiple electrical pulses generate rotating electric fields which introduce transient pores in the living cell without killing the cell. The rotating electric fields are provided in a flow through chamber apparatus having more than two electrodes. A three-step pulse process, e.g. collection, electroporation, electrophoresis, is used to introduce the preselected molecule into the cell. A mechanical means of repositioning cells between successive pulses is also provided. The apparatus can also provide a means to pulse cells at different temperatures and then after pulsing, let the cells recover for a specified residence time at another temperature.
摘要翻译：一种通过使细胞与预选分子接触并向细胞施加多系列电脉冲将预选分子引入活细胞的方法和装置。该方法可以离体使用。多个电脉冲产生旋转电场，其在活细胞中引入瞬时孔而不杀死细胞。旋转电场设置在具有多于两个电极的流通室装置中。三步脉冲处理，例如收集，电穿孔，电泳，用于将预选分子引入细胞。还提供了在连续脉冲之间重新定位电池的机械装置。该装置还可以提供在不同温度下脉冲细胞的手段，然后在脉冲之后，让细胞在另一个温度恢复指定的停留时间。

10. 发明授权

US06216034B1 Method of programming an array of needle electrodes for electroporation therapy of tissue 有权
标题翻译：编织电极阵列的方法，用于组织的电穿孔治疗
公开(公告)号：US06216034B1
公开(公告)日：2001-04-10
申请号：US09227417
申请日：1999-01-08
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 , A61B2018/143 , 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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