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    Composition and methods for enhancing receptor-mediated cellular internalization
    1.
    再颁专利
    Composition and methods for enhancing receptor-mediated cellular internalization 有权
    用于增强受体介导的细胞内化的组合物和方法

    公开(公告)号：USRE41996E1

    公开(公告)日：2010-12-14

    申请号：US11821513

    申请日：2007-06-21

    申请人： Daniel R. Deaver ,  David A. Edwards ,  Robert S. Langer

    发明人： Daniel R. Deaver ,  David A. Edwards ,  Robert S. Langer

    IPC分类号： A61F2/02 ,  A61F13/02 ,  A61K9/48 ,  A61K9/20 ,  A61K9/14

    CPC分类号： A61K9/0046 ,  A61K9/0031 ,  A61K9/0034 ,  A61K9/0043 ,  A61K9/006 ,  A61K9/0073 ,  A61K9/06 ,  A61K31/56 ,  A61K31/573 ,  A61K31/715 ,  A61K47/38 ,  A61K48/00 ,  A61K48/0008 ,  A61K48/0083 ,  Y10S977/906

    摘要： Compositions and methods for improving cellular internalization of one or more compounds are disclosed. The compositions include a compound to be delivered and a biocompatible viscous material, such as a hydrogel, lipogel, or highly viscous sol. The composition also include, or are administered in conjunction with, an enhancer in an amount effective to maximize expression of or binding to receptors and enhance RME of the compound into the cells. This leads to high transport rates of compounds to be delivered across cell membranes, facilitating more efficient delivery of drugs and diagnostic agents. Compositions are applied topically orally, nasally, vaginally, rectally, and ocularly. The enhancer is administered with the composition or separately, either systemically or preferably locally. The compound to be delivered can also be the enhancer.

    摘要翻译： 公开了用于改善一种或多种化合物的细胞内化的组合物和方法。 组合物包括待递送的化合物和生物相容的粘性材料，例如水凝胶，脂凝胶或高粘度溶胶。 该组合物还包括或者与增效剂一起施用，其量可以有效地最大程度地使受体的表达或结合，并增强化合物进入细胞的RME。 这导致要跨细胞膜递送的化合物的高传输速率，有助于更有效地递送药物和诊断剂。 组合物经口，鼻，阴道，直肠和眼部局部应用。 增强剂与组合物一起施用或分开施用，全部或优选局部施用。 待递送的化合物也可以是增强剂。

    Materials and methods for enhancing cellular internalization
    2.
    发明授权
    Materials and methods for enhancing cellular internalization 失效
    用于增强细胞内化的材料和方法

    公开(公告)号：US5985320A

    公开(公告)日：1999-11-16

    申请号：US810275

    申请日：1997-03-03

    申请人： David A. Edwards ,  Daniel R. Deaver ,  Robert S. Langer

    发明人： David A. Edwards ,  Daniel R. Deaver ,  Robert S. Langer

    IPC分类号： A61K9/06 ,  A61K9/00 ,  A61K9/127 ,  A61K31/70 ,  A61K31/7088 ,  A61K38/00 ,  A61K38/22 ,  A61K38/43 ,  A61K38/55 ,  A61K39/395 ,  A61K47/10 ,  A61K47/26 ,  A61K47/32 ,  A61K47/36 ,  A61K47/38 ,  A61K48/00 ,  A61K49/00

    CPC分类号： A61K9/0043 ,  A61K47/38 ,  A61K9/0034 ,  A61K47/10 ,  A61K47/26 ,  A61K47/36 ,  Y10S436/829

    摘要： Compositions and methods for delivering agents across cell membranes are disclosed. The compositions include an agent to be delivered, a viscous material, such as a hydrogel, lipogel or viscous sol, and, optionally, a carrier that includes a ligand that binds to or interacts with cell surface receptors. The agent to be delivered binds to or otherwise interacts with cell surface receptors, is attached, either covalently or ionically to a molecule that binds to or interacts with a cell surface receptor, or is associated with the carrier. Agents to be delivered include bioactive compounds and diagnostic agents. The compositions have an apparent viscosity roughly equal to the viscosity of the cytosol in the cell to which the agent is to be delivered. The rate of cellular internalization is higher when the viscosity of the viscous material and that of the cytosol in the cell are approximately the same, relative to when they are not the same. The compositions enhance cellular entry of bioactive agents and diagnostic materials when administered vaginally, nasally, rectally ocularly, orally, or to the respiratory or pulmonary system.

    摘要翻译： 公开了用于递送细胞膜的药剂的组合物和方法。 组合物包括待递送的试剂，粘性物质，例如水凝胶，脂凝胶或粘稠溶胶，以及任选的包含与细胞表面受体结合或与细胞表面受体相互作用的配体的载体。 待递送的药剂与细胞表面受体结合或以其他方式相互作用，与结合细胞表面受体或与细胞表面受体相关的分子共价或离子地连接。 待递送的试剂包括生物活性化合物和诊断剂。 组合物的表观粘度大致等于试剂要递送的细胞中细胞溶胶的粘度。 当粘性物质和细胞质中的细胞溶胶的粘度相差不大时，细胞内化速率较高。 当阴道，鼻，直肠眼，口服或呼吸或肺部系统施用时，组合物增强生物活性剂和诊断材料的细胞进入。

    Compositions and methods for enhancing receptor-mediated cellular internalization
    3.
    再颁专利
    Compositions and methods for enhancing receptor-mediated cellular internalization 失效
    用于增强受体介导的细胞内化的组合物和方法

    公开(公告)号：USRE42072E1

    公开(公告)日：2011-01-25

    申请号：US11821514

    申请日：2007-06-21

    申请人： Daniel R. Deaver ,  David A. Edwards ,  Robert S. Langer

    发明人： Daniel R. Deaver ,  David A. Edwards ,  Robert S. Langer

    IPC分类号： A61F2/02 ,  A61F13/02 ,  A61K9/48 ,  A61K9/20 ,  A61K9/14

    CPC分类号： A61K9/0046 ,  A61K9/0031 ,  A61K9/0034 ,  A61K9/0043 ,  A61K9/006 ,  A61K9/0073 ,  A61K9/06 ,  A61K31/56 ,  A61K31/573 ,  A61K31/715 ,  A61K47/38 ,  A61K48/00 ,  A61K48/0008 ,  A61K48/0083 ,  Y10S977/906

    摘要： Compositions and methods for improving cellular internalization of one or more compounds are disclosed. The compositions include a compound to be delivered and a biocompatible viscous material, such as a hydrogel, lipogel, or highly viscous sol. The composition also include, or are administered in conjunction with, an enhancer in an amount effective to maximize expression of or binding to receptors and enhance RME of the compound into the cells. This leads to high transport rates of compounds to be delivered across cell membranes, facilitating more efficient delivery of drugs and diagnostic agents. Compositions are applied topically orally, nasally, vaginally, rectally, and ocularly. The enhancer is administered with the composition or separately, either systemically or preferably locally. The compound to be delivered can also be the enhancer.

    摘要翻译： 公开了用于改善一种或多种化合物的细胞内化的组合物和方法。 组合物包括待递送的化合物和生物相容的粘性材料，例如水凝胶，脂凝胶或高粘度溶胶。 该组合物还包括或与其结合使用，其量可以有效地最大化受体的表达或结合，并增强化合物进入细胞的RME。 这导致要跨细胞膜递送的化合物的高传输速率，有助于更有效地递送药物和诊断剂。 组合物经口，鼻，阴道，直肠和眼部局部应用。 增强剂与组合物一起施用或分开施用，全部或优选局部施用。 待递送的化合物也可以是增强剂。

    Compositions and methods for enhancing receptor-mediated cellular internalization
    4.
    再颁专利
    Compositions and methods for enhancing receptor-mediated cellular internalization 有权
    用于增强受体介导的细胞内化的组合物和方法

    公开(公告)号：USRE42012E1

    公开(公告)日：2010-12-28

    申请号：US11821512

    申请日：2007-06-21

    申请人： Daniel R. Deaver ,  David A. Edwards ,  Robert S. Langer

    发明人： Daniel R. Deaver ,  David A. Edwards ,  Robert S. Langer

    IPC分类号： A61F13/02

    CPC分类号： A61K9/0046 ,  A61K9/0031 ,  A61K9/0034 ,  A61K9/0043 ,  A61K9/006 ,  A61K9/0073 ,  A61K9/06 ,  A61K31/56 ,  A61K31/573 ,  A61K31/715 ,  A61K47/38 ,  A61K48/00 ,  A61K48/0008 ,  A61K48/0083 ,  Y10S977/906

    摘要： Compositions and methods for improving cellular internalization of one or more compounds are disclosed. The compositions include a compound to be delivered and a biocompatible viscous material, such as a hydrogel, lipogel, or highly viscous sol. The composition also include, or are administered in conjunction with, an enhancer in an amount effective to maximize expression of or binding to receptors and enhance RME of the compound into the cells. This leads to high transport rates of compounds to be delivered across cell membranes, facilitating more efficient delivery of drugs and diagnostic agents. Compositions are applied topically orally, nasally, vaginally, rectally, and ocularly. The enhancer is administered with the composition or separately, either systemically or preferably locally. The compound to be delivered can also be the enhancer.

    摘要翻译： 公开了用于改善一种或多种化合物的细胞内化的组合物和方法。 组合物包括待递送的化合物和生物相容的粘性材料，例如水凝胶，脂凝胶或高粘度溶胶。 该组合物还包括或与其结合使用，其量可以有效地最大化受体的表达或结合，并增强化合物进入细胞的RME。 这导致要跨细胞膜递送的化合物的高传输速率，有助于更有效地递送药物和诊断剂。 组合物经口，鼻，阴道，直肠和眼部局部应用。 增强剂与组合物一起施用或分开施用，全部或优选局部施用。 待递送的化合物也可以是增强剂。

    Aerodynamically light particles for pulmonary drug delivery
    8.
    发明授权
    Aerodynamically light particles for pulmonary drug delivery 失效
    用于肺部药物递送的空气动力学轻微颗粒

    公开(公告)号：US06977087B2

    公开(公告)日：2005-12-20

    申请号：US10090418

    申请日：2002-03-01

    申请人： David A. Edwards ,  Giovannia Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

    发明人： David A. Edwards ,  Giovannia Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdell Aziz Ben-Jebria ,  Robert S. Langer

    IPC分类号： A61K9/00 ,  A61K9/14 ,  A61K9/16 ,  A61K31/56 ,  A61K31/568 ,  A61K38/28

    CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/56 ,  A61K31/568 ,  A61K38/28

    摘要： Improved aerodynamically light particles for delivery to the pulmonary system, and methods for their preparation and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 μm and 30 μm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear α-hydroxy-acid polyester backbone having at least one amino acid group incorporated herein and at least on poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 μm, can be used for enhanced delivery of a therapeutic or diagnostic agent to the alveolar region of the lung. The aerodynamically light particles optionally can incorporate a therapeutic or diagnostic agent, and may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of a wide variety of incorporated agents.

    摘要翻译： 提供用于递送至肺系统的改善的空气动力学轻微颗粒，以及其制备和给药方法。 在优选的实施方案中，空气动力学轻微颗粒由可生物降解的材料制成，并且振实密度小于0.4g / cm 3，质量平均直径在5μm和30μm之间。 颗粒可以由可生物降解的材料如可生物降解的聚合物形成。 例如，颗粒可以由官能化的聚酯接枝共聚物形成，所述官能化聚酯接枝共聚物由具有至少一个引入本文的氨基酸基团和至少在从氨基酸延伸的聚（氨基酸）侧链上的直链α-羟基酸聚酯主链组成 集团在聚酯骨干。 在一个实施方案中，具有大平均直径（例如大于5μm）的空气动力学轻的颗粒可用于增强治疗或诊断剂递送至肺的肺泡区域。 空气动力学轻微颗粒任选地可以掺入治疗剂或诊断剂，并且可以有效地雾化用于给予呼吸道以允许各种并入药剂的全身或局部递送。

    Aerodynamically light particles for pulmonary drug delivery
    9.
    发明授权
    Aerodynamically light particles for pulmonary drug delivery 有权

    公开(公告)号：US06399102B1

    公开(公告)日：2002-06-04

    申请号：US09562988

    申请日：2000-05-01

    申请人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdellaziz Ben-Jebria ,  Robert S. Langer

    发明人： David A. Edwards ,  Giovanni Caponetti ,  Jeffrey S. Hrkach ,  Noah Lotan ,  Justin Hanes ,  Abdellaziz Ben-Jebria ,  Robert S. Langer

    IPC分类号： A61K914

    CPC分类号： A61K9/0075 ,  A61K9/1647 ,  A61K31/137

    摘要： Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cm3 and a mass mean diameter between 5 &mgr;m and 30 &mgr;m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear &agr;-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 &mgr;m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.