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公开(公告)号：US20080199957A1
公开(公告)日：2008-08-21
申请号：US12105983
申请日：2008-04-18
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
IPC分类号： C12N5/06
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontophoresis, and/or electrophoresis can also be used with the disrupting agents.
摘要翻译： 描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。 组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。 在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。 还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。 这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。 待递送的药剂可以是治疗和/或诊断剂。 增强交付如超声波，离子电渗疗法和/或电泳的治疗也可与破坏剂一起使用。
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公开(公告)号：US20110288238A1
公开(公告)日：2011-11-24
申请号：US13182756
申请日：2011-07-14
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
IPC分类号： C08F220/06 , C08F265/02 , C08F299/00
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophoresis can also be used with the disrupting agents.
摘要翻译： 描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。 组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。 在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。 还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声波，温度或其组合都有反应。 这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。 待递送的药剂可以是治疗和/或诊断剂。 增强递送的治疗如超声波，离子分离和/或电泳也可与破坏剂一起使用。
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公开(公告)号：US08846106B2
公开(公告)日：2014-09-30
申请号：US13182756
申请日：2011-07-14
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophoresis can also be used with the disrupting agents.
摘要翻译： 描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。 组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。 在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。 还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。 这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。 待递送的药剂可以是治疗和/或诊断剂。 增强递送的治疗如超声波，离子分离和/或电泳也可与破坏剂一起使用。
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公开(公告)号：US08003129B2
公开(公告)日：2011-08-23
申请号：US12105983
申请日：2008-04-18
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontophoresis, and/or electrophoresis can also be used with the disrupting agents.
摘要翻译： 描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。 组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。 在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。 还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。 这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。 待递送的药剂可以是治疗和/或诊断剂。 增强交付如超声波，离子电渗疗法和/或电泳的治疗也可与破坏剂一起使用。
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公开(公告)号：US07374778B2
公开(公告)日：2008-05-20
申请号：US10857626
申请日：2004-05-28
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophereis can also be used with the disrupting agents.
摘要翻译： 描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。 组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。 在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。 还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。 这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。 待递送的药剂可以是治疗和/或诊断剂。 还可以与破坏剂一起使用增强交付如超声，离子层析和/或电穿孔的处理。
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公开(公告)号：US06835393B2
公开(公告)日：2004-12-28
申请号：US09226044
申请日：1999-01-05
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , David Tirrell , Niren Murthy , Chantal Lackey , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , David Tirrell , Niren Murthy , Chantal Lackey , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter
IPC分类号： A61K9127
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophereis can also be used with the disrupting agents.
摘要翻译： 描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。 组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。 在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。 还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。 这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。 待递送的药剂可以是治疗和/或诊断剂。 增强递送的治疗如超声波，离子分离和/或电泳也可与破坏剂一起使用。
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公开(公告)号：US06444217B1
公开(公告)日：2002-09-03
申请号：US09844659
申请日：2001-04-25
IPC分类号： A61F202
CPC分类号： A61K9/0024 , A61K9/0009 , A61L31/16 , A61L2300/602
摘要： The present invention provides biomedical devices, such as implantable drug delivery devices that possess a surface layer adapted to retain, and controllably release, drug molecules for administration to a subject. The present invention also provides methods of delivering a drug to a subject, the methods utilizing biomedical devices of the invention.
摘要翻译： 本发明提供生物医学装置，例如可植入药物递送装置，其具有适于保持和可控地释放用于给予受试者的药物分子的表面层。 本发明还提供了将药物递送到受试者的方法，所述方法利用了本发明的生物医学装置。
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8.发明申请METHODS FOR CHARACTERIZING NONLINEAR FIELDS OF A HIGH-INTENSITY FOCUSED ULTRASOUND SOURCE AND ASSOCIATED SYSTEMS AND DEVICES 审中-公开用于表征高强度聚焦超声波源和相关系统和器件的非线性场的方法公开(公告)号：US20120302927A1
公开(公告)日：2012-11-29
申请号：US13479067
申请日：2012-05-23
申请人： Vera A. Khokhlova , Petr Yuldashev , Oleg A. Sapozhnikov , Michael R. Bailey , Lawrence A. Crum
发明人： Vera A. Khokhlova , Petr Yuldashev , Oleg A. Sapozhnikov , Michael R. Bailey , Lawrence A. Crum
IPC分类号： A61N7/00
CPC分类号： A61N7/02 , A61N2007/0065 , A61N2007/0095
摘要： The present technology is directed to methods for characterizing nonlinear ultrasound fields and associated systems and devices. In several embodiments, for example, a method of calculating output of a high intensity focused ultrasound (HIFU) device comprises treating a target site with a multi-element HIFU array. In some embodiments, the array comprises a generally spherical segment. The method can further include simulating a field of the array by setting a boundary condition for the array. The boundary condition can be set by simplifying at least one geometrical aspect of the generally spherical segment.
摘要翻译： 本技术涉及用于表征非线性超声场和相关系统和装置的方法。 在几个实施例中，例如，计算高强度聚焦超声（HIFU）装置的输出的方法包括用多元素HIFU阵列处理靶位点。 在一些实施例中，阵列包括大致球形的段。 该方法还可以包括通过设置数组的边界条件来模拟阵列的一个字段。 可以通过简化大致球形段的至少一个几何方面来设定边界条件。
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9.发明申请COUNTERTOP ULTRASOUND IMAGING DEVICE AND METHOD OF USING THE SAME FOR PATHOLOGY SPECIMEN EVALUATION 审中-公开计数器超声成像装置及其用于病理学样本评估的方法公开(公告)号：US20100226555A1
公开(公告)日：2010-09-09
申请号：US12716991
申请日：2010-03-03
CPC分类号： G01N29/0672 , A61B8/08 , A61B2017/3409 , A61B2017/3413 , A61B2090/367 , A61B2090/3987 , G01N29/225 , G01N2291/02475 , G01N2291/106 , G01S15/8918 , G01S15/8938
摘要： A tissue specimen imaging device, comprising: a container having an upwardly facing surface, adapted to receive a tissue specimen and a liquid, an ultrasound imaging assembly, adapted to automatically form a three dimensional image of the tissue specimen interior. In one preferred embodiment the device includes a transducer head that is automatically moved relative to the specimen.
摘要翻译： 一种组织标本成像装置，包括：适于接收组织样本和液体的向上表面的容器，适于自动形成组织样本内部的三维图像的超声成像组件。 在一个优选实施例中，该装置包括相对于试样自动移动的换能器头。
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10.发明授权公开(公告)号：US07686763B2
公开(公告)日：2010-03-30
申请号：US10770350
申请日：2004-02-02
CPC分类号： A61B8/12 , A61B8/06 , A61B8/0833 , A61B8/445 , A61B8/4483 , A61B8/481 , A61B8/483 , A61B2017/4216 , A61B2090/378 , A61N7/02
摘要： Ultrasound contrast agents are used to enhance imaging and facilitate HIFU therapy in four different ways. A contrast agent is used: (1) before therapy to locate specific vascular structures for treatment; (2) to determine the focal point of a HIFU therapy transducer while the HIFU therapy transducer is operated at a relatively low power level, so that non-target tissue is not damaged as the HIFU is transducer is properly focused at the target location; (3) to provide a positive feedback mechanism by causing cavitation that generates heat, reducing the level of HIFU energy administered for therapy compared to that required when a contrast agent is not used; and, (4) to shield non-target tissue from damage, by blocking the HIFU energy. Various combinations of these techniques can also be employed in a single therapeutic implementation.
摘要翻译： 超声造影剂用于增强成像，并以四种不同的方式促进HIFU治疗。 使用造影剂：（1）治疗前定位特异性血管结构进行治疗; （2）确定HIFU治疗传感器的焦点，同时HIFU治疗传感器在相对较低的功率水平下运行，使得非靶组织不被损坏，因为HIFU换能器被适当地聚焦在目标位置; （3）通过引起产生热量的空化来提供正反馈机制，与不使用造影剂时所需的HIFU能量相比，降低施用的HIFU能量水平; 和（4）通过阻止HIFU能量来屏蔽非靶组织免受损伤。 这些技术的各种组合也可以在单一治疗实施中使用。
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