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    Switching fluorescent nanoparticle probe and fluorescent particle imaging method using same
    1.
    发明授权
    Switching fluorescent nanoparticle probe and fluorescent particle imaging method using same 有权
    开关荧光纳米粒子探针和荧光颗粒成像方法使用相同

    公开(公告)号：US09370589B2

    公开(公告)日：2016-06-21

    申请号：US13818392

    申请日：2011-08-08

    申请人： Isao Hara ,  Eiichi Ozeki ,  Hideo Saji ,  Shunsaku Kimura ,  Masahiro Ono ,  Takashi Temma

    发明人： Isao Hara ,  Eiichi Ozeki ,  Hideo Saji ,  Shunsaku Kimura ,  Masahiro Ono ,  Takashi Temma

    IPC分类号： A61K9/14 ,  A61K49/00

    CPC分类号： A61K49/0089 ,  A61K49/0032 ,  A61K49/0093 ,  Y10S977/773 ,  Y10S977/927

    摘要： The present invention provides a novel fluorescent nanoparticle imaging probe having a switching function (a function to quench a fluorescent dye during nanoparticle preparation, and emit fluorescence during imaging). A switching fluorescent nanoparticle probe comprising: a molecular assembly composed of an amphiphilic block polymer having a hydrophilic block chain and a hydrophobic block chain; and a fluorescent dye encapsulated in the molecular assembly, wherein (a) the hydrophilic block chain comprises, as an essential hydrophilic structural unit, a unit selected from a sarcosine unit and an alkylene oxide unit, (b) the hydrophobic block chain comprises, as an essential hydrophobic structural unit, a unit selected from the group consisting of an amino acid unit and a hydroxylic acid unit, and (c) the fluorescent dye is a cyanine compound represented by the formula (I): and two or more molecules of the fluorescent dye are encapsulated in the single molecular assembly.

    摘要翻译： 本发明提供了具有开关功能（在纳米颗粒制备期间淬灭荧光染料并在成像期间发射荧光的功能）的新型荧光纳米颗粒成像探针。 一种开关荧光纳米颗粒探针，包括：由具有亲水嵌段链和疏水性嵌段链的两亲嵌段聚合物组成的分子组合; 以及包封在分子组合中的荧光染料，其中（a）所述亲水性嵌段链包含作为必需亲水性结构单元的选自肌氨酸单元和烯化氧单元的单元，（b）所述疏水性嵌段链包含： 必需的疏水结构单元，选自氨基酸单元和羟基酸单元的单元，和（c）荧光染料是由式（I）表示的花青化合物：和 荧光染料被封装在单分子组装中。

    SWITCHING FLUORESCENT NANOPARTICLE PROBE AND FLUORESCENT PARTICLE IMAGING METHOD USING SAME
    3.
    发明申请
    SWITCHING FLUORESCENT NANOPARTICLE PROBE AND FLUORESCENT PARTICLE IMAGING METHOD USING SAME 有权
    切换荧光纳米粒子探针和使用其的荧光颗粒成像方法

    公开(公告)号：US20130149252A1

    公开(公告)日：2013-06-13

    申请号：US13818392

    申请日：2011-08-08

    申请人： Isao Hara ,  Eiichi Ozeki ,  Hideo Saji ,  Shunsaku Kimura ,  Masahiro Ono ,  Takashi Temma

    发明人： Isao Hara ,  Eiichi Ozeki ,  Hideo Saji ,  Shunsaku Kimura ,  Masahiro Ono ,  Takashi Temma

    IPC分类号： A61K49/00

    CPC分类号： A61K49/0089 ,  A61K49/0032 ,  A61K49/0093 ,  Y10S977/773 ,  Y10S977/927

    摘要： The present invention provides a novel fluorescent nanoparticle imaging probe having a switching function (a function to quench a fluorescent dye during nanoparticle preparation, and emit fluorescence during imaging). A switching fluorescent nanoparticle probe comprising: a molecular assembly composed of an amphiphilic block polymer having a hydrophilic block chain and a hydrophobic block chain; and a fluorescent dye encapsulated in the molecular assembly, wherein (a) the hydrophilic block chain comprises, as an essential hydrophilic structural unit, a unit selected from a sarcosine unit and an alkylene oxide unit, (b) the hydrophobic block chain comprises, as an essential hydrophobic structural unit, a unit selected from the group consisting of an amino acid unit and a hydroxylic acid unit, and (c) the fluorescent dye is a cyanine compound represented by the formula (I): and two or more molecules of the fluorescent dye are encapsulated in the single molecular assembly.

    摘要翻译： 本发明提供了具有开关功能（在纳米颗粒制备期间淬灭荧光染料并在成像期间发射荧光的功能）的新型荧光纳米颗粒成像探针。 一种开关荧光纳米颗粒探针，包括：由具有亲水嵌段链和疏水性嵌段链的两亲嵌段聚合物组成的分子组合; 以及包封在分子组合中的荧光染料，其中（a）所述亲水性嵌段链包含作为必需亲水性结构单元的选自肌氨酸单元和烯化氧单元的单元，（b）所述疏水性嵌段链包含： 必需的疏水结构单元，选自氨基酸单元和羟基酸单元的单元，和（c）荧光染料是由式（I）表示的花青化合物：和 荧光染料被封装在单分子组装中。

    SWITCHING-TYPE FLUORESCENT NANOPARTICLE PROBE, AND FLUORESCENT MOLECULAR IMAGING METHOD USING SAME
    4.
    发明申请
    SWITCHING-TYPE FLUORESCENT NANOPARTICLE PROBE, AND FLUORESCENT MOLECULAR IMAGING METHOD USING SAME 有权
    切换型荧光纳米粒子探针和使用相同的荧光分子成像方法

    公开(公告)号：US20130336896A1

    公开(公告)日：2013-12-19

    申请号：US14002327

    申请日：2012-03-01

    申请人： Hideo Saji ,  Shunsaku Kimura ,  Masahiro Ono ,  Takashi Temma ,  Isao Hara ,  Eiichi Ozeki

    发明人： Hideo Saji ,  Shunsaku Kimura ,  Masahiro Ono ,  Takashi Temma ,  Isao Hara ,  Eiichi Ozeki

    IPC分类号： A61K49/00

    CPC分类号： A61K49/0054 ,  A61K49/0032 ,  A61K49/0034 ,  A61K49/0069 ,  A61K49/0093

    摘要： [Problem] To provide a novel fluorescent nanoparticle imaging probe having a switching function (a function to quench a fluorescent dye in a blood component and emit fluorescence in a tumor or an inflamed site to be imaged).[Solution] A fluorescent nanoparticle probe comprising: a molecular assembly composed of an amphiphilic block polymer having a hydrophilic block chain and a hydrophobic block chain; and a fluorescent dye encapsulated in the assembly, wherein (a) the hydrophilic block chain comprises, as an essential hydrophilic structural unit, a unit selected from a sarcosine unit and an alkylene oxide unit, (b) the hydrophobic block chain comprises, as an essential hydrophobic structural unit, a unit selected from the group consisting of an amino acid unit and a hydroxylic acid unit, and (c) the fluorescent dye is a polylactic acid-bound cyanine compound comprising: a fluorescent group represented by the formula (I): and a polylactic acid group having 5 to 50 lactic acid units, and two or more molecules of the fluorescent dye are encapsulated in the single molecular assembly.

    摘要翻译： [问题]提供具有切换功能（在血液成分中淬灭荧光染料并在肿瘤中发射荧光或成像的发炎部位的功能）的新型荧光纳米粒子成像探针。 [解决方案]荧光纳米颗粒探针，其包含：由具有亲水性嵌段链和疏水性嵌段链的两亲嵌段聚合物组成的分子组合; 以及包封在所述组件中的荧光染料，其中（a）所述亲水性嵌段链包含作为必需亲水性结构单元的选自肌氨酸单元和烯化氧单元的单元，（b）所述疏水性嵌段链包含作为 必要的疏水结构单元，选自氨基酸单元和羟基酸单元的单元，和（c）荧光染料是聚乳酸结合的花青化合物，包括：由式（I）表示的荧光基团， 和具有5〜50个乳酸单元的聚乳酸基团和2个以上的荧光染料分子被包封在单分子组装体中。

    NOVEL MOLECULAR ASSEMBLY, MOLECULAR PROBE FOR MOLECULAR IMAGING AND MOLECULAR PROBE FOR DRUG DELIVERY SYSTEM USING THE SAME, AND MOLECULAR IMAGING SYSTEM AND DRUG DELIVERY SYSTEM
    5.
    发明申请
    NOVEL MOLECULAR ASSEMBLY, MOLECULAR PROBE FOR MOLECULAR IMAGING AND MOLECULAR PROBE FOR DRUG DELIVERY SYSTEM USING THE SAME, AND MOLECULAR IMAGING SYSTEM AND DRUG DELIVERY SYSTEM 审中-公开
    新型分子装置，用于分子成像的分子探针和使用其的药物递送系统的分子探针和分子成像系统和药物递送系统

    公开(公告)号：US20110104056A1

    公开(公告)日：2011-05-05

    申请号：US12995415

    申请日：2009-06-04

    申请人： Isao Hara ,  Ryo Yamahara ,  Eiichi Ozeki ,  Eri Takeuchi ,  Shunsaku Kimura ,  Shinae Kondoh ,  Akira Makino ,  Fumihiko Yamamoto

    发明人： Isao Hara ,  Ryo Yamahara ,  Eiichi Ozeki ,  Eri Takeuchi ,  Shunsaku Kimura ,  Shinae Kondoh ,  Akira Makino ,  Fumihiko Yamamoto

    IPC分类号： A61K51/06 ,  A61K49/00 ,  A61K49/04

    CPC分类号： A61K51/06 ,  A61K9/5153 ,  A61K49/0032 ,  A61K49/0034 ,  A61K49/0054 ,  A61K49/0082 ,  A61K51/1234

    摘要： The present invention provides a molecular assembly which is less likely to accumulate in tissue other than cancer tissue, is highly safe for a living body, and can be prepared by a simple and safe method and whose particle size can be easily controlled. The present invention provides a molecular imaging system and a molecular probe useful for the system, and a drug delivery system and a molecular probe useful for the system. The present invention provides a method for preparing molecular assembly, by which the particle size of molecular assembly having a signal group or a drug can be arbitrarily controlled in order to allow the molecular assembly to effectively accumulate in cancer tissue by utilizing EPR effect. A molecular assembly comprising: an amphiphilic block polymer A comprising a hydrophilic block chain and a hydrophobic block chain having 10 or more lactic acid units; a hydrophobic polymer A2 having at least 10 or more lactic acid units; and/or a labeled polymer B comprising at least 10 or more lactic acid units and a labeling group.

    摘要翻译： 本发明提供了不太可能积聚在癌组织以外的组织中的分子组装，对于活体是高度安全的，并且可以通过简单且安全的方法制备，并且可以容易地控制其粒径。 本发明提供了可用于该系统的分子成像系统和分子探针，以及可用于该系统的药物递送系统和分子探针。 本发明提供一种制备分子组装的方法，通过该方法可以任意地控制具有信号组或药物的分子组装的粒度，以便通过利用EPR效应使分子组装有效地积聚在癌组织中。 一种分子组合物，其包含：包含亲水性嵌段链和具有10个或更多个乳酸单元的疏水性嵌段链的两亲嵌段聚合物A; 具有至少10个以上乳酸单元的疏水性聚合物A2; 和/或包含至少10个或更多个乳酸单元和标记基团的标记聚合物B。

    Amphiphilic substance, and drug delivery system and molecular imaging system using the same
    7.
    发明授权
    Amphiphilic substance, and drug delivery system and molecular imaging system using the same 有权
    两亲物质，药物输送系统和分子成像系统使用相同

    公开(公告)号：US08945526B2

    公开(公告)日：2015-02-03

    申请号：US11812131

    申请日：2007-06-15

    申请人： Hitoshi Akitsu ,  Eiichi Ozeki ,  Ryoji Fushimi ,  Shunsaku Kimura ,  Masashi Isozaki ,  Shigenori Nozawa

    发明人： Hitoshi Akitsu ,  Eiichi Ozeki ,  Ryoji Fushimi ,  Shunsaku Kimura ,  Masashi Isozaki ,  Shigenori Nozawa

    IPC分类号： A61K31/74 ,  C08G69/10 ,  A61K49/00 ,  B82Y5/00

    CPC分类号： C08G69/10 ,  A61K49/0034 ,  A61K49/0043 ,  A61K49/0052 ,  A61K49/0093 ,  B82Y5/00

    摘要： The present invention provides a novel amphiphilic substance, a nanoparticle using the novel amphiphilic substance, which can be used as a nanocarrier having high biocompatibility, a drug delivery system and a probe useful for the system, and, a molecular imaging system and a probe useful for the system. An amphiphilic block polymer comprising a hydrophilic block; and a hydrophobic block, wherein the hydrophilic block is a hydrophilic polypeptide chain having 10 or more sarcosine units, and the hydrophobic block is a hydrophobic molecular chain comprising units selected from the group consisting of amino acid units and hydroxyl acid units as essential structural units, and having 5 or more of the essential structural units.

    摘要翻译： 本发明提供一种新颖的两亲物质，使用该新型两亲性物质的纳米粒子，其可以用作具有高生物相容性的纳米载体，药物递送系统和可用于该系统的探针，以及分子成像系统和有用的探针 为系统。 包含亲水嵌段的两亲嵌段聚合物; 和疏水嵌段，其中所述亲水嵌段是具有10个或更多个肌氨酸单元的亲水性多肽链，疏水嵌段是包含选自氨基酸单元和羟基酸单元作为必需结构单元的单元的疏水分子链， 并具有5个以上的基本结构单元。

    Novel amphiphilic substance, and drug delivery system and molecular imaging system using the same
    8.
    发明申请
    Novel amphiphilic substance, and drug delivery system and molecular imaging system using the same 有权
    新型两亲物质，以及药物输送系统和分子成像系统使用相同

    公开(公告)号：US20080019908A1

    公开(公告)日：2008-01-24

    申请号：US11812131

    申请日：2007-06-15

    申请人： Hitoshi Akitsu ,  Eiichi Ozeki ,  Ryoji Fushimi ,  Shunsaku Kimura ,  Masashi Isozaki ,  Shigenori Nozawa

    发明人： Hitoshi Akitsu ,  Eiichi Ozeki ,  Ryoji Fushimi ,  Shunsaku Kimura ,  Masashi Isozaki ,  Shigenori Nozawa

    IPC分类号： A61K49/00 ,  A61K38/00 ,  A61P43/00 ,  C07K14/00

    CPC分类号： C08G69/10 ,  A61K49/0034 ,  A61K49/0043 ,  A61K49/0052 ,  A61K49/0093 ,  B82Y5/00

    摘要： The present invention provides a novel amphiphilic substance, a nanoparticle using the novel amphiphilic substance, which can be used as a nanocarrier having high biocompatibility, a drug delivery system and a probe useful for the system, and, a molecular imaging system and a probe useful for the system. An amphiphilic block polymer comprising a hydrophilic block; and a hydrophobic block, wherein the hydrophilic block is a hydrophilic polypeptide chain having 10 or more sarcosine units, and the hydrophobic block is a hydrophobic molecular chain comprising units selected from the group consisting of amino acid units and hydroxyl acid units as essential structural units, and having 5 or more of the essential structural units.

    摘要翻译： 本发明提供一种新颖的两亲物质，使用该新型两亲性物质的纳米粒子，其可以用作具有高生物相容性的纳米载体，药物递送系统和可用于该系统的探针，以及分子成像系统和有用的探针 为系统。 包含亲水嵌段的两亲嵌段聚合物; 和疏水嵌段，其中所述亲水嵌段是具有10个或更多个肌氨酸单元的亲水性多肽链，疏水嵌段是包含选自氨基酸单元和羟基酸单元作为必需结构单元的单元的疏水分子链， 并具有5个以上的基本结构单元。

    BRANCHED AMPHIPATHIC BLOCK POLYMER AND MOLECULAR AGGREGATE AND DRUG DELIVERY SYSTEM USING SAME
    10.
    发明申请
    BRANCHED AMPHIPATHIC BLOCK POLYMER AND MOLECULAR AGGREGATE AND DRUG DELIVERY SYSTEM USING SAME 有权
    使用相同的分支片剂聚合物和分子聚集体和药物递送系统

    公开(公告)号：US20140127132A1

    公开(公告)日：2014-05-08

    申请号：US14126803

    申请日：2012-06-22

    申请人： Eiichi Ozeki ,  Shunsaku Kimura ,  Akira Makino

    发明人： Eiichi Ozeki ,  Shunsaku Kimura ,  Akira Makino

    IPC分类号： A61K49/00 ,  A61K47/34

    CPC分类号： A61K49/0054 ,  A61K9/1075 ,  A61K9/5153 ,  A61K47/34 ,  A61K47/641 ,  A61K49/0002 ,  A61K49/0034 ,  A61K49/0082 ,  A61K49/124 ,  B82Y40/00 ,  C08G69/44 ,  C08G83/005 ,  C08G83/008 ,  C08L101/005 ,  Y10S424/16 ,  Y10T428/2982

    摘要： Provided is a polymeric micelle pharmaceutical preparation that can increase the ratio of contrast at tumor site to background contrast in a short period of time after administration of a lactosome and can suppress the ABC phenomenon so that the lactosome can be administered more than once within a short span. A branched-type amphiphilic block polymer comprising: a multi-branched hydrophilic block comprising sarcosine; and a hydrophobic block comprising polylactic acid. The branched-type amphiphilic block polymer, wherein the number of branches of the hydrophilic block is 3. A molecular assembly comprising the branched-type amphiphilic block polymer. The molecular assembly further comprising a linear type amphiphilic block polymer.

    摘要翻译： 提供了一种聚合物胶束药物制剂，其可以在施用乳糖体后在短时间内增加肿瘤部位的对比度与背景对比度的比例，并且可以抑制ABC现象，使得在短时间内可以多次施用 跨度。 一种支链型两亲嵌段聚合物，其包含：包含肌氨酸的多支链亲水嵌段; 和包含聚乳酸的疏水嵌段。 支链型两亲性嵌段聚合物，其中亲水嵌段的分支数为3.包含支链型两亲性嵌段聚合物的分子组合物。 分子组合还包含线性型两亲嵌段聚合物。