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    Sonophoretic enhanced transdermal transport
    2.
    发明授权
    Sonophoretic enhanced transdermal transport 失效
    超声波增强透皮运输

    公开(公告)号：US06190315B1

    公开(公告)日：2001-02-20

    申请号：US09227623

    申请日：1999-01-08

    申请人： Joseph Kost ,  Samir S. Mitragotri ,  Robert S. Langer

    发明人： Joseph Kost ,  Samir S. Mitragotri ,  Robert S. Langer

    IPC分类号： A61B6520

    CPC分类号： A61M37/0092 ,  A61B5/14532 ,  A61M2037/0007

    摘要： Methods for enhanced transdermal transport wherein the application of ultrasound is required only once for repeated or sustained transdermal extraction or delivery, over a period of time, rather than prior to each extraction or delivery. The method is applicable to analyte extraction, as well as for drug delivery. The method involves the initial application of an amount of low frequency ultrasound effective to permeabilize the skin or membrane followed by analyte extraction or drug delivery over a period of time. The initial application of ultrasound is effective to permeabilize the skin or membrane for at least about 30 minutes, preferably at least one to two hours, and more preferably up to four to ten hours. The ultrasound is preferably low frequency ultrasound, less than 2.5 MHz, more preferably less than 1 MHz. The transdermal transport can be enhanced by the application of a secondary driving force such as suction, osmotic pressure gradient, concentration gradient, iontophoresis, electroporation, magnetic field, additional ultrasound, or mechanical pressure.

    摘要翻译： 用于增强透皮转运的方法，其中在一段时间内而不是在每次提取或递送之前，仅需要超声应用一次以重复或持续经皮提取或递送。 该方法适用于分析物提取以及药物递送。 该方法包括初始应用一定量的低频超声，其有效地使皮肤或膜透化，随后经过一段时间的分析物提取或药物递送。 超声的初始应用有效地使皮肤或膜透化至少约30分钟，优选至少1至2小时，更优选至多4至10小时。 超声波优选为低频超声波，小于2.5MHz，更优选小于1MHz。 可以通过施加诸如吸力，渗透压梯度，浓度梯度，离子电渗疗法，电穿孔，磁场，附加超声或机械压力的次级驱动力来增强透皮转运。

    Chemical and physical enhancers and ultrasound for transdermal drug delivery
    3.
    发明授权
    Chemical and physical enhancers and ultrasound for transdermal drug delivery 失效
    用于透皮给药的化学和物理增强剂和超声波

    公开(公告)号：US5947921A

    公开(公告)日：1999-09-07

    申请号：US574377

    申请日：1995-12-18

    申请人： Mark E. Johnson ,  Samir S. Mitragotri ,  Daniel Blankschtein ,  Robert S. Langer ,  Michael Pishko ,  Joseph Kost

    发明人： Mark E. Johnson ,  Samir S. Mitragotri ,  Daniel Blankschtein ,  Robert S. Langer ,  Michael Pishko ,  Joseph Kost

    IPC分类号： A61K9/00 ,  A61K41/00 ,  A61M37/00 ,  A61N1/32 ,  A61B17/00

    CPC分类号： A61B5/14514 ,  A61K41/0047 ,  A61K9/0009 ,  A61M37/0092 ,  A61N1/325 ,  A61N1/327 ,  A61M2037/0007

    摘要： Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by providing chemical enhancers which increase the solubility of the compound to be transported and/or lipid bilayer solubility, and/or additional driving forces for transport, such as mechanical or osmotic pressure, magnetic fields, 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 and other forces or concentrations than that required if each means of enhancing transport is used individually.

    摘要翻译： 可以通过提供增加待运输的化合物和/或脂质双层溶解度的溶解度的化学增强剂和/或用于运输的附加驱动力（例如机械或渗透）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 压力，磁场，电穿孔或离子电渗疗法。 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，允许快速控制经皮通量，并允许在较低的超声强度下进行药物递送或分析物提取，以及如果分别使用增强转运的每种手段所需的其他力或浓度。

    Introduction of modifying agents into skin by electroporation
    4.
    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。

    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
    7.
    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。