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1. 发明授权

US5458140A Enhancement of transdermal monitoring applications with ultrasound and chemical enhancers 失效
标题翻译：用超声波和化学增强剂增强透皮监护应用
公开(公告)号：US5458140A
公开(公告)日：1995-10-17
申请号：US152442
申请日：1993-11-15
申请人： Jonathan A. Eppstein , Deborah A. Eppstein , Joseph Kost , Robert S. Langer
发明人： Jonathan A. Eppstein , Deborah A. Eppstein , Joseph Kost , Robert S. Langer
IPC分类号： A61B5/00 , A61B17/00 , A61B18/20 , A61K41/00 , A61K49/22 , A61M37/00
CPC分类号： A61B5/1486 , A61B5/14514 , A61B5/681 , A61K41/0047 , A61K49/22 , A61B18/203 , A61B2017/00172 , A61B2017/00765 , A61B2018/00452 , A61B2018/0047 , A61B2562/0295 , A61M2037/0007 , A61M37/0092
摘要： A method of enhancing the permeability of the skin or mucosa to an analyte for diagnostic purposed is described utilizing ultrasound or ultrasound plus a chemical enhancer. If desired the ultrasound may be modulated by means of frequency modulation, amplitude modulation, phase modulation and/or combinations thereof. A frequency modulation from low to high develops a local pressure gradient directed out of the body, thus permitting analytes in the body to traverse the skin and be collected and measured outside the body. The concentration of an analyte in the body is preferably determined by enhancing the permeability of the skin or other biological membrane optionally with a chemical enhancer, applying ultrasound optionally at a modulated frequency, amplitude, phase, or combinations thereof that further induces a local pressure gradient out of the body, collecting the analyte, and utilizing the analyte collection data calculating the concentration of the analyte in the body.
摘要翻译：使用超声波或超声波加上化学增强剂来描述增强皮肤或粘膜对于诊断用途分析物的渗透性的方法。如果需要，可以通过频率调制，幅度调制，相位调制和/或其组合来调制超声波。从低到高的频率调制产生了引导出身体的局部压力梯度，从而允许身体中的分析物穿过皮肤并在体外被收集和测量。体内分析物的浓度优选通过任选地用化学增强剂增强皮肤或其他生物膜的渗透性，任选地以调制的频率，幅度，相位或其组合施加超声来进一步诱导局部压力梯度来确定收集分析物，并利用分析物收集数据计算体内分析物的浓度。

2. 发明授权

US4948587A Ultrasound enhancement of transbuccal drug delivery 失效
标题翻译：超声提高了跨颊药物的输送
公开(公告)号：US4948587A
公开(公告)日：1990-08-14
申请号：US233590
申请日：1988-08-18
申请人： Joseph Kost , Robert S. Langer
发明人： Joseph Kost , Robert S. Langer
IPC分类号： A61K9/00 , A61K41/00 , A61M35/00 , A61M37/00
CPC分类号： A61K41/0047 , A61K9/0009 , A61M37/00 , A61M37/0092 , A61M35/00
摘要： A method using ultrasound for enhancing and controlling transbuccal permeation of a molecule, including drugs, antigens, vitamins, inorganic and organic compounds, and various combinations of these substances, through the buccal membranes and into the circulatory system. The frequency and intensity of ultrasonic energy which is applied, and the length of time of exposure are determined according to the location and nature of the buccal membrane and the substance to be infused. Levels of the infused molecules in the blood and urine measured over a period of time are initially used to determine under what conditions optimum transfer occurs. In a variation of the method, whereby ultrasound is applied directly to the compound and site where the compound is to be infused through the buccal membranes, the compound can be placed within a delivery device. In one variation, the ultrasound can control release both by direct interaction with the compound and membrane but also with the delivery device. In another variation, the delivery device helps to modulate release and infusion rate. The compound can also be administered in combination with a chemical agent which alters permeability of the buccal membrane, thereby aiding infusion of the compound into the circulatory system.
摘要翻译：一种使用超声波增强和控制分子（包括药物，抗原，维生素，无机和有机化合物）以及这些物质的各种组合的跨颊渗透通过颊膜进入循环系统的方法。应用超声能量的频率和强度以及暴露时间长短根据颊膜和待注射物质的位置和性质来确定。在一段时间内测量的血液和尿液中输注的分子的水平最初用于确定什么条件下最佳转移发生。在该方法的变型中，由此将超声波直接施加到化合物和通过颊膜输注化合物的部位，化合物可以放置在输送装置内。在一个变化中，超声波可以通过与化合物和膜的直接相互作用来控制释放，而且还可以通过递送装置控制释放。在另一个实施例中，递送装置有助于调节释放和输注速率。化合物还可以与改变颊膜渗透性的化学试剂组合施用，由此帮助化合物输注到循环系统中。

3. 发明授权

US4779806A Ultrasonically modulated polymeric devices for delivering compositions 失效
标题翻译：用于输送组合物的超声波调制聚合物装置
公开(公告)号：US4779806A
公开(公告)日：1988-10-25
申请号：US936000
申请日：1986-11-28
申请人： Robert S. Langer , Joseph Kost
发明人： Robert S. Langer , Joseph Kost
IPC分类号： A61K9/00 , A61K9/20 , A61K41/00 , C08G67/04 , B02C19/18
CPC分类号： A61K9/0009 , A61K41/0047 , A61K9/2027 , A61K9/2031 , C08G67/04
摘要： A composition such as a biologically active substance is delivered upon demand from a polymeric matrix by exposing the polymeric matrix containing the composition to ultrasonic energy.
摘要翻译：通过将含有该组合物的聚合物基体暴露于超声波能量，可以根据需要从聚合物基质递送诸如生物活性物质的组合物。

4. 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。

5. 发明授权

US4767402A Ultrasound enhancement of transdermal drug delivery 失效
标题翻译：超声增强透皮给药
公开(公告)号：US4767402A
公开(公告)日：1988-08-30
申请号：US883111
申请日：1986-07-08
申请人： Joseph Kost , Drora Levy , Robert S. Langer
发明人： Joseph Kost , Drora Levy , Robert S. Langer
IPC分类号： A61M35/00 , A61K9/00 , A61K41/00 , A61M37/00 , A61B17/20
CPC分类号： A61M37/0092 , A61K41/0047 , A61K9/0009 , A61M35/00
摘要： The present invention is a method using ultrasound to enhance permeation of molecules through the skin and into the blood stream, at a controlled rate. Depending on the drug being infused through the skin, the rate of permeation is increased as well as the efficiency of transfer. Drugs which may not be effective under other conditions, for example, due to degradation within the gastrointestinal tract, can be effectively conveyed transdermally into the circulatory system by means of ultrasound.
摘要翻译：本发明是一种使用超声波以可控制的速度增强分子穿过皮肤并进入血液的渗透的方法。根据通过皮肤注入的药物，渗透速率以及转移效率也提高。在其它条件下可能不起作用的药物，例如由于胃肠道内的降解，可以通过超声波有效地传递到循环系统中。

6. 发明授权

US4657543A Ultrasonically modulated polymeric devices for delivering compositions 失效
公开(公告)号：US4657543A
公开(公告)日：1987-04-14
申请号：US633366
申请日：1984-07-23
申请人： Robert S. Langer , Joseph Kost
发明人： Robert S. Langer , Joseph Kost
IPC分类号： A61K9/00 , A61K9/20 , A61K9/22 , A61K41/00 , A61L27/50 , C08G67/04
CPC分类号： A61K9/0009 , A61K41/0047 , A61K9/2027 , A61K9/2031 , A61L27/50 , C08G67/04
摘要： A composition such as a biologically active substance is delivered upon demand from a polymeric matrix by exposing the polymeric matrix containing the composition to ultrasonic energy.

7. 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。

8. 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。

9. 发明授权

US4780212A Ultrasound enchancement of membrane permeability 失效
标题翻译：超声增强膜渗透性
公开(公告)号：US4780212A
公开(公告)日：1988-10-25
申请号：US80325
申请日：1987-07-31
申请人： Joseph Kost , Robert S. Langer
发明人： Joseph Kost , Robert S. Langer
IPC分类号： A61M37/00 , B01D61/00 , B01D61/24 , B01D63/16 , B01D13/00
CPC分类号： B01D61/243 , A61M37/0092 , B01D61/00 , B01D63/16
摘要： A method for enhancing or controlling permeability of large molecular weight molecules in a membrane system wherein molecules in solution are contacted with membranes and the system is exposed to ultrasound at a selected intensity and frequency and for a specific length of time. The method may be designed to insure that only reversible changes in the membrane result from exposure to the ultrasound or to enhance the rate of degradation of the membrane and/or selectivity of passage of molecules through the membrane. The method may include selection of the membrane composition and structure, including the pore size, thickness, crystallinity and molecular arrangement. Selection of the solvent or media in which the molecules are suspended may be used to further enhance or control permeability. The media may be either an aqueous or inorganic solution with the physical and chemical properties may be selected to attenuate sound transmission or to enhance stability of the molecule permeating the membrane.
摘要翻译：一种用于增强或控制膜系统中大分子量分子的渗透性的方法，其中溶液中的分子与膜接触，并且系统以选定的强度和频率暴露于超声波并且持续特定长度的时间。该方法可以设计成确保膜中的可逆变化仅由暴露于超声波或增加膜的降解速率和/或分子通过膜的通过的选择性而产生。该方法可以包括膜组成和结构的选择，包括孔径，厚度，结晶度和分子排列。可以使用悬浮分子的溶剂或介质的选择来进一步增强或控制渗透性。介质可以是水溶液或无机溶液，其物理和化学性质可以被选择以减弱声音传播或提高透过膜的分子的稳定性。

10. 发明授权

US10696944B2 Intracellular delivery 有权
公开(公告)号：US10696944B2
公开(公告)日：2020-06-30
申请号：US14352354
申请日：2012-10-17
申请人： Massachusetts Institute of Technology , Armon R. Sharei , Andrea Adamo , Robert S. Langer , Klavs F. Jensen
发明人： Armon R. Sharei , Andrea Adamo , Robert S. Langer , Klavs F. Jensen
IPC分类号： C12N5/071 , C12M1/42 , C12M3/06 , C12N15/87 , B82Y5/00
摘要： A microfluidic system for causing perturbations in a cell membrane, the system including a microfluidic channel defining a lumen and being configured such that a cell suspended in a buffer can pass therethrough, wherein the microfluidic channel includes a cell-deforming constriction, wherein a diameter of the constriction is a function of the diameter of the cell.

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