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    • 1. 发明申请
    • ENHANCED TRANSPORT USING MEMBRANE DISRUPTIVE AGENTS
    • 使用薄膜破坏剂加强运输
    • US20110288238A1
    • 2011-11-24
    • US13182756
    • 2011-07-14
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • C08F220/06C08F265/02C08F299/00
    • A61K47/481A61K41/0028A61K41/0047A61K47/48376A61K47/6801
    • 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.
    • 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。
    • 2. 发明申请
    • ENHANCED TRANSPORT USING MEMBRANE DISRUPTIVE AGENTS
    • 使用薄膜破坏剂加强运输
    • US20080199957A1
    • 2008-08-21
    • US12105983
    • 2008-04-18
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • C12N5/06
    • A61K47/481A61K41/0028A61K41/0047A61K47/48376A61K47/6801
    • 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.
    • 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。
    • 3. 发明授权
    • Enhanced transport using membrane disruptive agents
    • 增强运输使用膜破坏剂
    • US06835393B2
    • 2004-12-28
    • US09226044
    • 1999-01-05
    • Allan S. HoffmanPatrick StaytonOliver W. PressDavid TirrellNiren MurthyChantal LackeyLawrence A. CrumPierre D. MouradTyrone M. Porter
    • Allan S. HoffmanPatrick StaytonOliver W. PressDavid TirrellNiren MurthyChantal LackeyLawrence A. CrumPierre D. MouradTyrone M. Porter
    • A61K9127
    • A61K47/481A61K41/0028A61K41/0047A61K47/48376A61K47/6801
    • 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.
    • 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。
    • 4. 发明授权
    • Enhanced transport using membrane disruptive agents
    • 增强运输使用膜破坏剂
    • US08846106B2
    • 2014-09-30
    • US13182756
    • 2011-07-14
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • A61K9/14A61K9/16A61K47/00A61K41/00A61K47/48
    • A61K47/481A61K41/0028A61K41/0047A61K47/48376A61K47/6801
    • 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.
    • 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。
    • 5. 发明授权
    • Enhanced transport using membrane disruptive agents
    • 增强运输使用膜破坏剂
    • US08003129B2
    • 2011-08-23
    • US12105983
    • 2008-04-18
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • A61K9/14A61K9/16A61K47/00A61K9/127
    • A61K47/481A61K41/0028A61K41/0047A61K47/48376A61K47/6801
    • 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.
    • 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。
    • 6. 发明授权
    • Enhanced transport using membrane disruptive agents
    • 增强运输使用膜破坏剂
    • US07374778B2
    • 2008-05-20
    • US10857626
    • 2004-05-28
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • Allan S. HoffmanPatrick StaytonOliver W. PressNiren MurthyChantal Lackey ReedLawrence A. CrumPierre D. MouradTyrone M. PorterDavid Tirrell
    • A61K9/127A61K9/14A61K9/16A61K47/00
    • A61K47/481A61K41/0028A61K41/0047A61K47/48376A61K47/6801
    • 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.
    • 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。