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    Introduction of modifying agents into skin by electroporation
    1.
    发明授权
    Introduction of modifying agents into skin by electroporation 失效
    通过电穿孔将改性剂引入皮肤

    公开(公告)号：US5911223A

    公开(公告)日：1999-06-15

    申请号：US695367

    申请日：1996-08-09

    申请人： James C. Weaver ,  Tani Chen ,  Christopher Cullander ,  Richard Guy ,  Robert S. Langer ,  Thomas E. Zewert ,  Uwe Pliquett ,  Rita Vanbever ,  Mark R. Prausnitz

    发明人： James C. Weaver ,  Tani Chen ,  Christopher Cullander ,  Richard Guy ,  Robert S. Langer ,  Thomas E. Zewert ,  Uwe Pliquett ,  Rita Vanbever ,  Mark R. Prausnitz

    IPC分类号： A61B17/00 ,  A61N1/32 ,  A61B19/00

    CPC分类号： A61N1/0424 ,  A61N1/325 ,  A61B2017/00765 ,  A61N1/0428 ,  Y10S607/901

    摘要： A method of modifying epidermis for transport of a material by electroporation includes applying to epidermis an agent that, upon entry into the epidermis, will modify the epidermis to thereby cause and altered rate of transport of a material across the epidermis. Typically, the altered rate will be an increased rate of transport. The epidermis is electroporated, whereby at least a portion of the modifying agent enters the electroporated epidermis, thereby modifying the epidermis to cause an altered rate of transport of a material across the epidermis. In another embodiment, the modifying agent can modify the epidermis to enable measurement and/or monitoring of physiological conditions or change within or beneath the epidermis. The modifying agents can also be employed to facilitate discharge of fluids from within an organism, such as by providing pathways for discharge of fluids from a tumor. Examples of modifying agents include: oxidizing agents; reducing agents; particles, such as optical indicator beads or beads that include drugs to be released into tissue; electrically-charged particles or molecules; etc. Materials that can be transported by the method of the invention include, for example, proteins, nucleic acids, electrically charged molecules or particles, microorganisms suitable for immunization, etc. Also, tissues other than skin can be employed in the method of the invention.

    摘要翻译： 通过电穿孔来改变用于运输材料的表皮的方法包括向表皮施加一种在进入表皮时将改变表皮从而引起和改变材料穿过表皮的运输速率的试剂。 通常，改变率将是增加的运输速度。 表皮被电穿孔，由此至少一部分改性剂进入电穿孔表皮，从而改变表皮，导致材料穿过表皮的转运速率。 在另一个实施方案中，修饰剂可以修饰表皮以使得能够测量和/或监测生理条件或在表皮内或下表面的变化。 还可以使用改性剂来促进从生物体内排出流体，例如通过提供从肿瘤排出流体的途径。 改性剂的实例包括：氧化剂; 还原剂; 颗粒，例如包括要释放到组织中的药物的光学指示剂珠粒或珠粒; 带电粒子或分子; 可以通过本发明的方法传输的材料包括例如蛋白质，核酸，带电分子或颗粒，适合免疫的微生物等。另外，皮肤以外的组织可以用于 发明。

    Biopotential measurement including electroporation of tissue surface
    3.
    发明授权
    Biopotential measurement including electroporation of tissue surface 失效
    生物电位测量，包括组织表面的电穿孔

    公开(公告)号：US6085115A

    公开(公告)日：2000-07-04

    申请号：US83497

    申请日：1998-05-22

    申请人： James C. Weaver ,  Uwe Pliquett ,  Rita Vanbever ,  Thiruvallur R. Gowrishankar ,  Thomas E. Zewert

    发明人： James C. Weaver ,  Uwe Pliquett ,  Rita Vanbever ,  Thiruvallur R. Gowrishankar ,  Thomas E. Zewert

    IPC分类号： A61B5/0402 ,  A61B5/04

    CPC分类号： A61B5/04025

    摘要： A method for measuring biopotential of an organism includes electroporating a portion of a tissue surface of the organism. The biopotential of the organism is then measured with electrodes at the electroporated portion of the organism. The portion of the organism that is electroporated can be, for example, a skin surface of the organism. A resistance-decreasing agent, such as heparin, sodium thiosulfate, thioglycolic acid solution and dithioglycolic acid can be applied to the tissue surface to facilitate reduction in electrical resistance. Another example of a resistance-decreasing agent is a keratin-disrupting agent, such as sulforhodamine. Examples of suitable biopotential measurements include electrocardiographic, electroencephalographic, electromyographic, electrohysterographic and elctrokymographic measurements. The method decreases skin resistance to diminish unwanted electrical voltages that compete with biopotential measurements, thereby significantly improving the biopotential measurement.

    摘要翻译： 用于测量生物体的生物潜力的方法包括电穿孔生物体的组织表面的一部分。 然后用生物体的电穿孔部分的电极测量生物体的生物潜力。 电穿孔的生物体的部分可以是例如生物体的皮肤表面。 电阻降低剂如肝素，硫代硫酸钠，巯基乙酸溶液和二硫代乙醇酸可以施加到组织表面以便于降低电阻。 抗性降低剂的另一个实例是角蛋白破坏剂，例如磺酰罗丹明。 合适的生物电位测量的实例包括心电图，脑电图，肌电描记术，电积电图和电压测量。 该方法降低皮肤抵抗力，减少与生物电位测量竞争的不需要的电压，从而显着改善生物电位测量。

    Method for rapid temporal control of molecular transport across tissue
    5.
    发明授权
    Method for rapid temporal control of molecular transport across tissue 失效
    快速时间控制组织分子转运的方法

    公开(公告)号：US5667491A

    公开(公告)日：1997-09-16

    申请号：US487470

    申请日：1995-06-07

    申请人： Uwe Pliquett ,  Mark R. Prausnitz ,  James C. Weaver ,  Robert S. Langer

    发明人： Uwe Pliquett ,  Mark R. Prausnitz ,  James C. Weaver ,  Robert S. Langer

    IPC分类号： A61B5/00 ,  A61K38/38 ,  A61K38/48 ,  A61K41/00 ,  A61K48/00 ,  A61N1/32 ,  C07K14/82 ,  C12N15/87 ,  A61M31/00

    CPC分类号： A61N1/0412 ,  A61B5/14514 ,  A61B5/418 ,  A61K31/00 ,  A61K41/0047 ,  A61K48/00 ,  A61N1/325 ,  A61N1/327 ,  C07K14/82 ,  C12N15/87 ,  G01N33/50 ,  A61B5/14532 ,  A61N1/0452

    摘要： A method is disclosed for treating tissue in response to a stimulus generated by the tissue. In one embodiment, the method transdermally treats an organism in response to a stimulus. In this embodiment, the medication is applied to epidermis of the organism, and the epidermis is electroporated in response to a stimulus, whereby the medication passes through the epidermis at a rate sufficient to alter the stimulus, thereby transdermally treating the organism. In another embodiment, the method measures a blood component content of blood. A portion of epidermis is electroporated to cause an aqueous fluid to be directed through an electroporated epidermis to a surface of the epidermis. Thereafter, the blood component content of the aqueous fluid is measured for correlation with a known aqueous fluid blood component content associated with a known concentration of blood component in the blood. The blood component concentration of the blood can thereby be measured. In still another embodiment, the method includes directing a medication to the tissue which can alter the stimulus when the tissue is electroporated, and electroporating the tissue in response to a stimulus, whereby the medication passes through the tissue in an amount sufficient to alter the stimulus, thereby treating the organism.

    摘要翻译： 公开了一种响应于由组织产生的刺激来治疗组织的方法。 在一个实施方案中，所述方法响应于刺激经皮处理生物体。 在该实施方案中，将药物施用于生物体的表皮，并且响应于刺激而对表皮进行电穿孔，由此药物以足以改变刺激的速率通过表皮，从而透皮治疗生物体。 在另一个实施方案中，该方法测量血液的血液成分含量。 将一部分表皮电穿孔以使含水液体通过电穿孔表皮导入表皮表面。 此后，测量含水流体的血液成分含量与已知的血液中血液成分浓度相关的含水液体成分含量的相关性。 因此可以测量血液的血液成分浓度。 在另一个实施方案中，该方法包括将药物引导到组织，当组织被电穿孔时可以改变刺激，并响应于刺激电穿孔组织，由此药物以足以改变刺激的量通过组织 ，从而治疗生物体。

    Method for rapid temporal control of molecular transport across tissue
    6.
    发明授权
    Method for rapid temporal control of molecular transport across tissue 失效
    快速时间控制跨组织分子转运的方法

    公开(公告)号：US5547467A

    公开(公告)日：1996-08-20

    申请号：US096512

    申请日：1993-07-23

    申请人： Uwe Pliquett ,  Mark R. Prausnitz ,  James C. Weaver ,  Robert S. Langer

    发明人： Uwe Pliquett ,  Mark R. Prausnitz ,  James C. Weaver ,  Robert S. Langer

    IPC分类号： A61B5/00 ,  A61K38/38 ,  A61K38/48 ,  A61K41/00 ,  A61K48/00 ,  A61N1/32 ,  C07K14/82 ,  C12N15/87 ,  A61M37/00

    CPC分类号： A61N1/0412 ,  A61B5/14514 ,  A61B5/418 ,  A61K31/00 ,  A61K41/0047 ,  A61K48/00 ,  A61N1/325 ,  A61N1/327 ,  C07K14/82 ,  C12N15/87 ,  G01N33/50 ,  A61B5/14532 ,  A61N1/0452

    摘要： A method is disclosed for treating tissue in response to a stimulus generated by the tissue. In one embodiment, the method transdermally treats an organism in response to a stimulus. In this embodiment, the medication is applied to epidermis of the organism, and the epidermis is electroporated in response to a stimulus, whereby the medication passes through the epidermis at a rate sufficient to alter the stimulus, thereby transdermally treating the organism. In another embodiment, the method measures a blood component content of blood. A portion of epidermis is electroporated to cause an aqueous fluid to be directed through an electroporated epidermis to a surface of the epidermis. Thereafter, the blood component content of the aqueous fluid is measured for correlation with a known aqueous fluid blood component content associated with a known concentration of blood component in the blood. The blood component concentration of the blood can thereby be measured. In still another embodiment, the method includes directing a medication to the tissue which can alter the stimulus when the tissue is electroporated, and electroporating the tissue in response to a stimulus, whereby the medication passes through the tissue in an amount sufficient to alter the stimulus, thereby treating the organism.

    摘要翻译： 公开了一种响应于由组织产生的刺激来治疗组织的方法。 在一个实施方案中，所述方法响应于刺激经皮处理生物体。 在该实施方案中，将药物施用于生物体的表皮，并且响应于刺激而对表皮进行电穿孔，由此药物以足以改变刺激的速率通过表皮，从而透皮治疗生物体。 在另一个实施方案中，该方法测量血液的血液成分含量。 将一部分表皮电穿孔以使含水液体通过电穿孔表皮导入表皮表面。 此后，测量含水流体的血液成分含量与已知的血液中血液成分浓度相关的含水液体成分含量的相关性。 因此可以测量血液的血液成分浓度。 在另一个实施方案中，该方法包括将药物引导到组织，当组织被电穿孔时可以改变刺激，并响应于刺激电穿孔组织，由此药物以足以改变刺激的量通过组织 ，从而治疗生物体。

    Apparatus and method for electroporation of tissue
    7.
    发明授权
    Apparatus and method for electroporation of tissue 失效
    用于组织电穿孔的装置和方法

    公开(公告)号：US5983131A

    公开(公告)日：1999-11-09

    申请号：US695032

    申请日：1996-08-09

    申请人： James C. Weaver ,  Uwe Pliquett ,  Timothy Vaughan

    发明人： James C. Weaver ,  Uwe Pliquett ,  Timothy Vaughan

    IPC分类号： A61N1/30 ,  A61N1/32

    CPC分类号： A61N1/0424 ,  A61N1/327 ,  A61N1/044

    摘要： The present invention relates to an apparatus and method for localized electroporation of tissue. An apparatus includes a perforate electrically insulating layer, a first electrode at a first side of the perforate electrically insulating layer and a second electrode at a second side of the perforate electrically insulating layer. An electric field extending between the first and second electrodes will preferentially extend through perforations of the electrically insulating layer. The electric field thereby causes electroporation of tissue that is proximate to the first electrode and is partitioned from the electrically insulating layer and the second electrode by the first electrode. The apparatus controllably limits the depth of the electric field within a tissue, such as skin, thereby electroporating a surface layer, such as a stratum corneum layer of the skin, without stimulating submerged nerve endings within the skin. Sensation of the applied voltage and especially pain sensation can thereby be controlled by the invention.

    摘要翻译： 本发明涉及组织局部电穿孔的装置和方法。 一种装置包括穿孔电绝缘层，在穿孔电绝缘层的第一侧的第一电极和在穿孔电绝缘层的第二侧的第二电极。 在第一和第二电极之间延伸的电场将优先延伸穿过电绝缘层的穿孔。 电场因此导致组织的电穿孔，其接近第一电极，并且通过第一电极与电绝缘层和第二电极分隔开。 该装置可控制地限制组织（例如皮肤）内的电场的深度，由此电穿孔皮肤的表层，例如皮肤角质层，而不刺激皮肤内的淹没的神经末梢。 因此，本发明可以控制施加电压的感觉，特别是疼痛感。