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1. 发明授权

US5911223A Introduction of modifying agents into skin by electroporation 失效
标题翻译：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。

2. 发明授权

US6085115A Biopotential measurement including electroporation of tissue surface 失效
标题翻译：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。

3. 发明授权

US5749847A Delivery of nucleotides into organisms by electroporation 失效
标题翻译：通过电穿孔将核苷酸递送到生物体中
公开(公告)号：US5749847A
公开(公告)日：1998-05-12
申请号：US471642
申请日：1995-06-06
申请人： Thomas E. Zewert , Uwe Pliquett , Robert S. Langer , James C. Weaver
发明人： Thomas E. Zewert , Uwe Pliquett , Robert S. Langer , James C. Weaver
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： C12N15/87 , A61B5/14514 , A61K38/385 , A61K38/48 , A61K38/4873 , A61K41/0047 , A61K48/00 , A61N1/325 , A61N1/327 , C07K14/82 , A61B5/14532
摘要： A method for delivering a nucleotide into an organism includes applying a composition which includes a nucleotide component to epidermis of the organism. The epidermis is electroporated, whereby at least a portion of the composition enters or passes across the epidermis, thereby delivering the nucleotide into the organism. An example of a suitable nucleotide which can be delivered by the method of the invention includes antisense oligodeoxynucleotides for treatment of melanomas.
摘要翻译：将核苷酸递送至生物体的方法包括将包含核苷酸组分的组合物施用于生物体的表皮。电穿孔表皮，由此组合物的至少一部分进入或穿过表皮，从而将核苷酸输送到生物体内。可以通过本发明的方法递送的合适的核苷酸的实例包括用于治疗黑素瘤的反义寡脱氧核苷酸。

4. 发明授权

US5667491A Method for rapid temporal control of molecular transport across tissue 失效
标题翻译：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。

5. 发明授权

US5547467A Method for rapid temporal control of molecular transport across tissue 失效
标题翻译：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。

6. 发明授权

US6041253A Effect of electric field and ultrasound for transdermal drug delivery 失效
标题翻译：电场和超声对透皮给药的影响
公开(公告)号：US6041253A
公开(公告)日：2000-03-21
申请号：US626021
申请日：1996-04-01
申请人： Joseph Kost , Uwe Pliquett , Samir S. Mitragotri , Robert S. Langer , James C. Weaver
发明人： Joseph Kost , Uwe Pliquett , Samir S. Mitragotri , Robert S. Langer , James C. Weaver
IPC分类号： A61K9/00 , A61K41/00 , A61M37/00 , A61N1/32 , A61N1/30
CPC分类号： A61N1/325 , A61B5/14514 , A61K41/0047 , A61K9/0009 , A61M37/0092 , A61N1/0412 , A61N1/327 , A61M2037/0007 , A61N1/042 , A61N1/0428
摘要： Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by application of an electric field, for example, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field.
摘要翻译：可以通过施加电场（例如电穿孔或离子电渗疗法）来进一步增强超声波输送（递送或提取）期间分子的透皮转运。在优选实施例中，超声是低频超声，其引起角质层（SC）的脂质层的空化。该方法提供较高的药物透皮通量，允许快速控制透皮通量，并且能够在不存在电场的情况下以较低的超声强度进行药物递送或分析物提取。

7. 发明授权

US5983131A Apparatus and method for electroporation of tissue 失效
标题翻译：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。

8. 发明授权

US5019034A Control of transport of molecules across tissue using electroporation 失效
标题翻译：使用电穿孔控制分子跨组织的运输
公开(公告)号：US5019034A
公开(公告)日：1991-05-28
申请号：US331263
申请日：1989-03-30
申请人： James C. Weaver , Kevin T. Powell , Robert S. Langer, Jr.
发明人： James C. Weaver , Kevin T. Powell , Robert S. Langer, Jr.
IPC分类号： A61N1/30 , A61B5/00 , A61B10/02 , A61K41/00 , A61M37/00 , A61N1/32
CPC分类号： A61B5/14514 , A61K41/0047 , A61N1/0412 , A61N1/325 , A61N1/327 , A61B5/14532 , A61N1/0424 , A61N1/044
摘要： An electrical process for enhancing and/or controlling transport of molecules across tissue such as human and animal skin is disclosed. The process involves the use of a high voltage, short duration electrical pulses on the tissue surface to produce electroporation. Once this effect has occurred, concentration, pressure or temperature gradients, or iontopheresis can be used to move molecules across the tissue. The process can be repeatedly applied without producing undesirable tissue damage or can be used to purposely cause highly limited tissue damage for the purpose of providing a desired, relatively long term molecular transport pathway. The occurrence of the electroporation effect can be detected by monitoring the tissue for a reversible electrical breakdown, which, along with an enhanced tissue permeability, is the characteristic effect of electroporation.
摘要翻译：公开了用于增强和/或控制分子穿过诸如人和动物皮肤的组织的电工艺。该过程涉及在组织表面上使用高电压，短持续时间的电脉冲以产生电穿孔。一旦发生这种影响，可以使用浓度，压力或温度梯度，或离子透析法来移动分子穿过组织。该方法可以重复施加而不产生不期望的组织损伤，或者可以用于故意地引起高度有限的组织损伤以提供期望的相对长期的分子转运途径。电穿孔效应的发生可以通过监测组织的可逆电击穿来检测，其与增强的组织渗透性一起是电穿孔的特征效应。

9. 发明授权

US4699942A Polyester compositions 失效
标题翻译：聚酯组合物
公开(公告)号：US4699942A
公开(公告)日：1987-10-13
申请号：US770939
申请日：1985-08-30
申请人： James C. Weaver , Wayne P. Pruett
发明人： James C. Weaver , Wayne P. Pruett
IPC分类号： C08K3/04 , C08K3/34 , C08K5/13 , C08L67/02 , C08K13/02 , C08K5/01
CPC分类号： C08K3/34 , C08K3/04 , C08K5/13 , C08L67/02
摘要： Compositions suitable for molding are produced by examining a (1) polyethylene terephthalate polyester, (2) a low molecular weight polyethylene mold release agent (3) talc as nucleating agent, (4) carbon black, (5) a hindered phenolic antioxidant and (6) other optional ingredients such as reinforcing glass fibers.
摘要翻译：通过检查（1）聚对苯二甲酸乙二醇酯聚酯，（2）低分子量聚乙烯脱模剂（3）作为成核剂的滑石粉，（4）炭黑，（5）受阻酚抗氧化剂和（ 6）其他任选成分如增强玻璃纤维。

10. 发明授权

US5640169A Protected antenna apparatus 失效
标题翻译：保护天线装置
公开(公告)号：US5640169A
公开(公告)日：1997-06-17
申请号：US546701
申请日：1995-10-23
申请人： James C. Weaver
发明人： James C. Weaver
IPC分类号： H01Q1/42
CPC分类号： H01Q1/42
摘要： A protected antenna apparatus including an elongated tube; a cable having an upper end with a pair of separate bare leads extending therefrom, a lower end with a connector secured thereto, and an intermediate portion extended between the ends; a twin-lead transmission line having a central axis, a free upper end, a lower end with the bare leads extending therefrom and interconnected together, an intermediate location therebetween wherein each lead is connected with one of the bare leads of the cable, and a notch formed on an upper extent of the line at a location between the intermediate location and the upper end to thereby divide one of the leads into two different pieces and thus create a J-pole antenna having a short leg, a long leg, and an impedance matching stub portion therebetween, and wherein the antenna transmits radio signals of a characteristic frequency as a function of the lengths of the legs and the stub portion; and a coupling mechanism for securing the antenna within the tube and along a longitudinal extent thereof.
摘要翻译：一种受保护的天线装置，包括细长管; 电缆，其上端具有从其延伸的一对单独的裸露引线，具有固定到其上的连接器的下端和在端部之间延伸的中间部分; 双引线传输线，具有中心轴线，自由上端，下端，裸引线从其延伸并互连在一起，其间的中间位置，其中每个引线与电缆的裸线之一连接，形成在中间位置和上端之间的位置处的线的上部范围上的凹口，从而将引线中的一个分成两个不同的部分，从而形成具有短腿，长腿和其间的阻抗匹配短截线部分，并且其中天线将特征频率的无线电信号作为腿部和短截线部分的长度传播; 以及用于将天线固定在管内并沿其纵向范围的联接机构。

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