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1. 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。

2. 发明授权

US06190315B1 Sonophoretic enhanced transdermal transport 失效
标题翻译：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。

3. 发明授权

US5947921A Chemical and physical enhancers and ultrasound for transdermal drug delivery 失效
标题翻译：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。

4. 发明授权

US06234990B1 Ultrasound enhancement of transdermal transport 失效
标题翻译：超声增强透皮运输
公开(公告)号：US06234990B1
公开(公告)日：2001-05-22
申请号：US08885931
申请日：1997-06-30
申请人： Stephen Rowe , Joseph Kost , Samir S. Mitragotri , Michael Pishko , Matthew Davis
发明人： Stephen Rowe , Joseph Kost , Samir S. Mitragotri , Michael Pishko , Matthew Davis
IPC分类号： A61B1720
CPC分类号： A61B5/14514 , A61B5/150022 , A61B5/150083 , A61B5/150099 , A61B5/150137 , A61B5/150259 , A61B5/150389 , A61B5/150969 , A61B5/150984 , A61B5/15136 , A61M37/0092 , A61M2037/0007
摘要： Methods and devices for application of ultrasound to a small area of skin for enhancing transdermal transport. An ultrasound beam having a first focal diameter is channelled into a beam having a second, smaller diameter without substantial loss of energy. Higher energy ultrasound can be used while causing less pain. Alternatively, ultrasound energy is applied through a vibrating element positioned just contacting, above or extending into the skin. Use of the element facilitates extraction of analyte and may enhance drug delivery. A two step noninvasive method involves application of ultrasound to increase skin permeability and removal of ultrasound followed by transdermal transport that can be further enhanced using a physical enhancer.
摘要翻译：将超声应用于小面积皮肤以增强透皮运输的方法和装置。具有第一焦距的超声波束被引导到具有第二较小直径的光束中，而实质上没有能量损失。可以使用更高能量的超声波，同时减少疼痛。或者，通过刚刚接触皮肤上方或延伸到皮肤的振动元件施加超声能量。元素的使用有助于提取分析物，并且可以增强药物递送。两步非侵入性方法涉及应用超声波以增加皮肤渗透性和去除超声，然后进行透皮转运，其可以使用物理增强剂进一步增强。

5. 发明授权

US06887239B2 Preparation for transmission and reception of electrical signals 有权
标题翻译：准备发送和接收电信号
公开(公告)号：US06887239B2
公开(公告)日：2005-05-03
申请号：US10411156
申请日：2003-04-11
申请人： Tuan A. Elstrom , Scott Kellogg , Joseph Kost , Samir S. Mitragotri , Nicolas F. Warner , Steve DiMatteo
发明人： Tuan A. Elstrom , Scott Kellogg , Joseph Kost , Samir S. Mitragotri , Nicolas F. Warner , Steve DiMatteo
IPC分类号： A61B5/05 , A61B5/04 , A61B5/0408 , A61B5/053 , A61B8/00 , A61N1/08 , A61N7/00 , A61B18/18
CPC分类号： A61B8/4281 , A61B5/0048 , A61B5/04 , A61B5/0531 , A61B8/4236 , A61B8/4455 , A61N1/08 , A61N7/00
摘要： The invention provides a convenient and non-invasive means to prepare cells, tissues, and organs for electrical transmission and reception. In an embodiment of the invention, a control method comprises the use of at least one skin electrode, as a reference electrode, and an electrical sensor to measure periodically or continuously the skin's electrical conductance at the site of preparation. The dynamic change in the conductance through the skin is measured while the ultrasound is applied. Signal processing is performed on the measurement and the level of skin impedance change is controlled by performing a mathematical analysis and using the results of such analysis to control the application of ultrasonic energy. A desired level of skin impedance can be set at a predetermined value or based on a chosen level of skin integrity, subject's sensation of discomfort, or duration of the ultrasound application.
摘要翻译：本发明提供了用于制备用于电传输和接收的细胞，组织和器官的方便和非侵入性的手段。在本发明的一个实施例中，控制方法包括使用至少一个皮肤电极作为参比电极，以及电传感器，用于周期性或连续地测量皮肤在制备部位的导电性。当施加超声波时，测量通过皮肤的电导的动态变化。对测量进行信号处理，并且通过执行数学分析并使用这种分析的结果来控制超声能量的应用来控制皮肤阻抗变化的水平。可以将期望水平的皮肤阻抗设定在预定值或基于所选择的皮肤完整程度，受试者的不适感或超声应用的持续时间。

6. 发明申请

US20130035566A1 Method and Apparatus for Enhancement of Transdermal Transport 有权
标题翻译：用于增强透皮转运的方法和装置
公开(公告)号：US20130035566A1
公开(公告)日：2013-02-07
申请号：US13614032
申请日：2012-09-13
申请人： Samir S. Mitragotri , Joseph Kost , Scott C. Kellogg , Nicholas F. Warner , Tuan A. Elstrom
发明人： Samir S. Mitragotri , Joseph Kost , Scott C. Kellogg , Nicholas F. Warner , Tuan A. Elstrom
IPC分类号： A61M37/00 , A61B5/157
CPC分类号： A61K49/0004 , A61M37/0092
摘要： According to the present invention, a method for enhancing transdermal transport is disclosed. The method includes the steps of increasing a permeability an area of a membrane with a permeabilizing device. The membrane may be, inter alia, biologic skin or synthetic skin. The permeabilizing device may be an ultrasound-producing device. A substance is transported into and through the area the membrane. The substance may be a drug, a vaccine, or a component of interstitial fluid.
摘要翻译：根据本发明，公开了一种增强透皮转运的方法。该方法包括通过透化装置增加膜的面积的渗透性的步骤。膜可以是生物皮肤或合成皮肤。渗透装置可以是超声产生装置。物质被运送进入膜并通过该区域。该物质可以是药物，疫苗或组织液的组分。

7. 发明授权

US08870810B2 Method and apparatus for enhancement of transdermal transport 有权
标题翻译：用于增强透皮运输的方法和装置
公开(公告)号：US08870810B2
公开(公告)日：2014-10-28
申请号：US13614032
申请日：2012-09-13
申请人： Samir S. Mitragotri , Joseph Kost , Scott C. Kellogg , Nicholas F Warner , Tuan A Elstrom
发明人： Samir S. Mitragotri , Joseph Kost , Scott C. Kellogg , Nicholas F Warner , Tuan A Elstrom
IPC分类号： A61B17/20 , A61M31/00
CPC分类号： A61K49/0004 , A61M37/0092
摘要： According to the present invention, a method for enhancing transdermal transport is disclosed. The method includes the steps of increasing a permeability an area of a membrane with a permeabilizing device. The membrane may be, inter alia, biologic skin or synthetic skin. The permeabilizing device may be an ultrasound-producing device. A substance is transported into and through the area the membrane. The substance may be a drug, a vaccine, or a component of interstitial fluid.
摘要翻译：根据本发明，公开了一种增强透皮转运的方法。该方法包括通过透化装置增加膜的面积的渗透性的步骤。膜可以是生物皮肤或合成皮肤。渗透装置可以是超声产生装置。物质被运送进入膜并通过该区域。该物质可以是药物，疫苗或组织液的组分。

8. 发明授权

US08287483B2 Method and apparatus for enhancement of transdermal transport 有权
标题翻译：用于增强透皮运输的方法和装置
公开(公告)号：US08287483B2
公开(公告)日：2012-10-16
申请号：US10792862
申请日：2004-03-05
申请人： Samir S. Mitragotri , Joseph Kost , Scott C. Kellogg , Nicholas F. Warner , Tuan A. Elstrom
发明人： Samir S. Mitragotri , Joseph Kost , Scott C. Kellogg , Nicholas F. Warner , Tuan A. Elstrom
IPC分类号： A61B17/20 , A61M31/00
CPC分类号： A61B5/411 , A61B5/14532 , A61B5/415 , A61B5/418 , A61K49/0004 , A61M37/0092 , A61M2037/0007
摘要： According to the present invention, a method for enhancing transdermal transport is disclosed. The method includes the steps of increasing a permeability of an area of a membrane with a permeabilizing device. The membrane may be, inter alia, biologic skin or synthetic skin. The permeabilizing device may be an ultrasound-producing device. A substance is transported into and through the area of the membrane. The substance may be a drug, a vaccine, or a component of interstitial fluid.
摘要翻译：根据本发明，公开了一种增强透皮转运的方法。该方法包括通过透化装置增加膜的面积的渗透性的步骤。膜可以是生物皮肤或合成皮肤。渗透装置可以是超声产生装置。物质被运送进入并通过膜的区域。该物质可以是药物，疫苗或组织液的组分。

9. 发明授权

US06620123B1 Method and apparatus for producing homogenous cavitation to enhance transdermal transport 失效
标题翻译：用于产生均匀空化以增强透皮转运的方法和装置
公开(公告)号：US06620123B1
公开(公告)日：2003-09-16
申请号：US09868443
申请日：2001-07-26
申请人： Samir S. Mitragotri , Joseph Kost , Scott C. Kellogg , Nicholas F. Warner
发明人： Samir S. Mitragotri , Joseph Kost , Scott C. Kellogg , Nicholas F. Warner
IPC分类号： A61B1720
CPC分类号： A61M37/0092 , A61B2017/22008 , A61B2017/22027 , A61B2017/320072
摘要： The present invention is directed to apparatus and methods for producing homogenous cavitation. An ultrasound souce comprising an ultrasound transmitting element having an axis and a cross-section along the axis is disclosed The ultrasound transmitting element also has a first axial end and a second axial end operable to produce ultrasonic waves. The cross-section has an area having a maximum value at the first axial end and a minimum value at the second axial end. A method for producing homogenous cavitation at an area of skin comprises creating a volume of fluid having a uniformly dispersed concentration of cavitation nuclei adjacent the area of skin. Ultrasound is then applied to the volume of fluid and causes cavitation at the cavitation nuclei.
摘要翻译：本发明涉及用于产生均匀空化的装置和方法。公开了一种包括具有沿轴线的轴线和横截面的超声波发射元件的超声波囊。超声波发射元件还具有可操作以产生超声波的第一轴向端和第二轴向端。横截面具有在第一轴向端具有最大值的区域和在第二轴向端处的最小值。用于在皮肤区域产生均匀空化的方法包括产生具有与皮肤区域相邻的气蚀核的均匀分散浓度的流体体积。然后将超声波施加到体积的流体并在空化核处引起空化。

10. 发明授权

US06491657B2 Ultrasound enhancement of transdermal transport 失效
标题翻译：超声增强透皮运输
公开(公告)号：US06491657B2
公开(公告)日：2002-12-10
申请号：US09861924
申请日：2001-05-21
申请人： Stephen Rowe , Joseph Kost , Samir S. Mitragotri , Michael Pishko , Matthew Davis
发明人： Stephen Rowe , Joseph Kost , Samir S. Mitragotri , Michael Pishko , Matthew Davis
IPC分类号： A61B1720
CPC分类号： A61B5/14514 , A61B5/150022 , A61B5/150083 , A61B5/150099 , A61B5/150137 , A61B5/150259 , A61B5/150389 , A61B5/150969 , A61B5/150984 , A61B5/15136 , A61M37/0092 , A61M2037/0007
摘要： Methods and devices for application of ultrasound to a small area of skin for enhancing transdermal transport. An ultrasound beam having a first focal diameter is channelled into a beam having a second, smaller diameter without substantial loss of energy. Higher energy ultrasound can be used while causing less pain. Alternatively, ultrasound energy is applied through a vibrating element positioned just contacting, above or extending into the skin. Use of the element facilitates extraction of analyte and may enhance drug delivery. A two step noninvasive method involves application of ultrasound to increase skin permeability and removal of ultrasound followed by transdermal transport that can be further enhanced using a physical enhancer.
摘要翻译：将超声应用于小面积皮肤以增强透皮运输的方法和装置。具有第一焦距的超声波束被引导到具有第二较小直径的光束中，而实质上没有能量损失。可以使用更高能量的超声波，同时减少疼痛。或者，通过刚刚接触皮肤上方或延伸到皮肤的振动元件施加超声能量。元素的使用有助于提取分析物，并且可以增强药物递送。两步非侵入性方法涉及应用超声波以增加皮肤渗透性和去除超声，然后进行透皮转运，其可以使用物理增强剂进一步增强。

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