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    Cancer cell diagnosis by targeting delivery of nanodevices
    1.
    发明授权
    Cancer cell diagnosis by targeting delivery of nanodevices 有权
    通过靶向纳米设备的递送进行癌细胞诊断

    公开(公告)号：US07976825B2

    公开(公告)日：2011-07-12

    申请号：US12315951

    申请日：2008-12-08

    申请人： Janos Borbely ,  Magdolna Bodnar ,  John F Hartmann ,  Istvan Hajdu ,  Jozsef Kollar ,  Gyorgy Vamosi

    发明人： Janos Borbely ,  Magdolna Bodnar ,  John F Hartmann ,  Istvan Hajdu ,  Jozsef Kollar ,  Gyorgy Vamosi

    IPC分类号： A61B5/055 ,  A61B49/04 ,  A61K9/50

    CPC分类号： A61K31/519 ,  A61K31/7088 ,  A61K49/1824 ,  B82Y5/00 ,  Y10S977/773 ,  Y10S977/93

    摘要： Macromolecular contrast agents for magnetic resonance imaging are described. Biomolecules and their modified derivatives form stable complexes with paramagnetic ions thus increasing the molecular relaxivity of carriers. The synthesis of biomolecular based nanodevices for targeted delivery of MRI contrast agents are described. Nanoparticles (NP) have been constructed by self-assembling of chitosan (CHIT) as polycation and poly-gamma glutamic acids (PGA) as polyanion. NP's are capable of Gd-ion uptake forming a particle with suitable molecular relaxivity. Folic acid (FA) is linked to the NP's to produce NP-FA bioconjugates that can be used for targeted in vitro delivery to a human cancer cell line.

    摘要翻译： 描述了用于磁共振成像的大分子造影剂。 生物分子及其修饰的衍生物与顺磁离子形成稳定的络合物，从而增加载体的分子弛豫性。 描述了用于靶向递送MRI造影剂的基于生物分子的纳米装置的合成。 纳米颗粒（NP）已经通过壳聚糖（CHIT）作为聚阳离子和聚-γ谷氨酸（PGA）作为聚阴离子自组装而构建。 NP能够进行Gd离子吸收，形成具有合适分子弛豫性的颗粒。 叶酸（FA）与NP连接以产生可用于靶向体外递送至人癌细胞系的NP-FA生物缀合物。

    Cancer cell diagnosis by targeting delivery of nanodevices
    2.
    发明申请
    Cancer cell diagnosis by targeting delivery of nanodevices 有权
    通过靶向纳米设备的递送进行癌细胞诊断

    公开(公告)号：US20090180966A1

    公开(公告)日：2009-07-16

    申请号：US12315951

    申请日：2008-12-08

    申请人： Janos Borbely ,  Magdolna Bodnar ,  John F. Hartmann ,  Istvan Hajdu ,  Jozsef Kollar ,  Gyorgy Vamosi

    发明人： Janos Borbely ,  Magdolna Bodnar ,  John F. Hartmann ,  Istvan Hajdu ,  Jozsef Kollar ,  Gyorgy Vamosi

    IPC分类号： A61K9/14 ,  A61P43/00

    CPC分类号： A61K31/519 ,  A61K31/7088 ,  A61K49/1824 ,  B82Y5/00 ,  Y10S977/773 ,  Y10S977/93

    摘要： Macromolecular contrast agents for magnetic resonance imaging are described. Biomolecules and their modified derivatives form stable complexes with paramagnetic ions thus increasing the molecular relaxivity of carriers. The synthesis of biomolecular based nanodevices for targeted delivery of MRI contrast agents are described. Nanoparticles (NP) have been constructed by self-assembling of chitosan (CHIT) as polycation and poly-gamma glutamic acids (PGA) as polyanion. NP's are capable of Gd-ion uptake forming a particle with suitable molecular relaxivity. Folic acid (FA) is linked to the NP's to produce NP-FA bioconjugates that can be used for targeted in vitro delivery to a human cancer cell line.

    摘要翻译： 描述了用于磁共振成像的大分子造影剂。 生物分子及其修饰的衍生物与顺磁离子形成稳定的络合物，从而增加载体的分子弛豫性。 描述了用于靶向递送MRI造影剂的基于生物分子的纳米装置的合成。 纳米颗粒（NP）已经通过壳聚糖（CHIT）作为聚阳离子和聚-γ谷氨酸（PGA）作为聚阴离子自组装而构建。 NP能够进行Gd离子吸收，形成具有合适分子弛豫性的颗粒。 叶酸（FA）与NP连接以产生可用于靶向体外递送至人癌细胞系的NP-FA生物缀合物。

    Polymeric nanoparticles by ion-ion interactions
    3.
    发明申请
    Polymeric nanoparticles by ion-ion interactions 审中-公开
    通过离子 - 离子相互作用的聚合物纳米颗粒

    公开(公告)号：US20080160096A1

    公开(公告)日：2008-07-03

    申请号：US11881831

    申请日：2007-07-27

    申请人： Janos Berbely ,  Magdolna Bodnar ,  Istvan Hajdu ,  John F. Hartmann ,  Zsolt Keresztessy ,  Laszlo Nagy ,  Gyorgy Vamosi

    发明人： Janos Berbely ,  Magdolna Bodnar ,  Istvan Hajdu ,  John F. Hartmann ,  Zsolt Keresztessy ,  Laszlo Nagy ,  Gyorgy Vamosi

    IPC分类号： A61K9/50

    CPC分类号： A61K9/5138 ,  A61K9/5015 ,  A61K9/5026 ,  A61K9/5036 ,  A61K9/5146 ,  A61K9/5161 ,  A61K9/5192 ,  C12N15/87

    摘要： The present invention relates to biocompatible and biodegradable stimuli-sensitive polymeric nanoparticles, which were formed by ion-ion interaction in aqueous media. Synthetic and biological macromolecules with ionizable functional groups are capable of forming nanoparticles whose size and surface properties are sensitive to environmental influences such as pH, temperature and salt concentration. Nanodevices are designed for therapeutic applications as drug and nucleic acid carriers, and/or for MRI diagnosis as contrast agents. These nanodevices are designed for therapeutic applications as targeted drug carriers. Additionally, they can be used as contrast agents for MRI diagnosis. These nanosystems are also potential carriers for delivery of active ingredients as DNA, RNA, short interfering RNA (siRNA), antisense oligonucleotides (AS-ON), and triple helix forming oligonucleotides (TFO) etc. for pharmaceutical applications. Their adjustable size offers yet another advantage.

    摘要翻译： 本发明涉及生物相容性和生物可降解的刺激性敏感的聚合物纳米粒子，其通过在水性介质中的离子 - 离子相互作用而形成。 具有可离子化官能团的合成和生物大分子能够形成尺寸和表面性质对pH，温度和盐浓度等环境影响敏感的纳米颗粒。 纳米设备设计用作药物和核酸载体的治疗应用，和/或作为造影剂的MRI诊断。 这些纳米设备被设计用作靶向药物载体的治疗应用。 此外，它们可以用作MRI诊断的造影剂。 这些纳米系统也是作为药物应用的DNA，RNA，短干扰RNA（siRNA），反义寡核苷酸（AS-ON）和三螺旋形成寡核苷酸（TFO）等递送活性成分的潜在载体。 它们的可调节尺寸提供了另一个优点。

    Polymeric nanoparticles by ion-ion Interactions
    4.
    发明申请
    Polymeric nanoparticles by ion-ion Interactions 审中-公开
    聚合物纳米粒子通过离子 - 离子相互作用

    公开(公告)号：US20080193547A1

    公开(公告)日：2008-08-14

    申请号：US12005643

    申请日：2007-12-27

    申请人： Janos Borbely ,  Magdolna Bodnar ,  Istvan Hajdu ,  John F. Hartmann

    发明人： Janos Borbely ,  Magdolna Bodnar ,  Istvan Hajdu ,  John F. Hartmann

    IPC分类号： A61K9/16 ,  A61K31/7088 ,  A61K31/519

    CPC分类号： A61K31/519 ,  A61K9/5146 ,  A61K9/5161 ,  A61K31/7088 ,  A61K47/6929 ,  A61K47/6933 ,  A61K47/6939 ,  A61K49/12 ,  A61K49/146 ,  A61K49/1818 ,  A61K49/1878 ,  B82Y5/00

    摘要： The present invention relates to biocompatible and biodegradable, stimuli sensitive, polymeric nanoparticles, which are formed by ion-ion interaction in aqueous media. Synthetic and biological macromolecules with ionizable functional groups are capable of forming nanoparticles whose size and surface properties are sensitive to environmental factors such as pH, temperature and salt concentration. Nanodevices made from these nanoparticles are designed for therapeutic applications included but not limited to use as drug carriers and/or used as contrast agents in MRI diagnosis and the like. The adjustable size of the nanodevices and their stimuli sensitivity allows specific delivery applications. Thus, these nanosystems are potential carrier tools for delivery of active ingredients such as drugs, as well as DNA, RNA, siRNA for cosmetics, pharmaceutical applications, etc.

    摘要翻译： 本发明涉及通过在水介质中离子 - 离子相互作用而形成的生物相容性和可生物降解的刺激敏感的聚合物纳米颗粒。 具有可离子化官能团的合成和生物大分子能够形成尺寸和表面性质对环境因素如pH，温度和盐浓度敏感的纳米颗粒。 由这些纳米颗粒制成的纳米装置设计用于治疗应用，包括但不限于用作药物载体和/或用作MRI诊断等中的造影剂。 纳米器件的可调节尺寸及其刺激灵敏度允许特定的输送应用。 因此，这些纳米系统是用于递送活性成分如药物的潜在载体工具，以及用于化妆品的DNA，RNA，siRNA，药物应用等。

    1,4-Disubstituted piperazines having dopaminergic activity
    8.
    发明授权
    1,4-Disubstituted piperazines having dopaminergic activity 失效
    具有多巴胺能活性的1,4-二取代哌嗪

    公开(公告)号：US4874765A

    公开(公告)日：1989-10-17

    申请号：US41206

    申请日：1987-04-22

    申请人： Erzsebet Lapis ,  Edit Toth ,  Bela Kiss ,  Jozsef Torley ,  Eva Palosi ,  Istvan Hajdu ,  Laszlo Szporny ,  Dora Groo ,  Istvan Laszlovszky

    发明人： Erzsebet Lapis ,  Edit Toth ,  Bela Kiss ,  Jozsef Torley ,  Eva Palosi ,  Istvan Hajdu ,  Laszlo Szporny ,  Dora Groo ,  Istvan Laszlovszky

    IPC分类号： C07D295/08 ,  A61K31/495 ,  A61P25/00 ,  A61P25/24 ,  A61P25/26 ,  C07D295/088 ,  C07D295/18 ,  C07D295/185 ,  C07D295/10

    CPC分类号： C07D295/185 ,  C07D295/088

    摘要： The invention relates to novel 1,4-disubstituted piperazine derivatives of the general formula (I), pharmaceutically acceptable acid addition and quaternary ammonium salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the general formula (I) ##STR1## R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are the same or different and stand for hydrogen or halogen or a trihalomethyl, lower alkyl, lower alkoxy, nitro, hydroxyl, aralkyloxy or an 1-(2-propenyl-4-piperazinyl) group;R.sub.5 stands for hydrogen or a C.sub.1-4 alkyl group;R.sub.6 represents a C.sub.3-6 alkyl, alkenyl, alkynyl group or a ##STR2## group, wherein R.sub.7 means a C.sub.2-5 alkyl, alkenyl or alkinyl group; andis 2 or 3,with the provisos that:R.sub.6 is different from isopropyl, n-butyl and isobutyl group when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-chloro and n is 2;R.sub.6 is different from isopropyl group when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-chloro and n is 2; or when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-methyl group and n is 2; andR.sub.6 is different from propionyl group when R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are hydrogen and n means 2.The compounds of the general formula (I) are therapeutically useful for the treatment of diseases arising from a hypofunction of the dopaminergic system.

    摘要翻译： 本发明涉及通式（I）的新的1,4-二取代哌嗪衍生物，其药学上可接受的酸加成盐和季铵盐，含有它们的药物组合物及其制备方法。 在通式（I）中，R 1，R 2，R 3和R 4相同或不同，代表氢或卤素或三卤代甲基，低级烷基，低级烷氧基，硝基，羟基，芳烷氧基或1- （2-丙烯基-4-哌嗪基）基团; R5代表氢或C1-4烷基; R6表示C3-6烷基，烯基，炔基或者IMAGE基团，其中R7表示C2-5烷基，烯基或炔基; 并且为2或3，条件是：当R 2，R 3，R 4和R 5代表氢时，R 6不同于异丙基，正丁基和异丁基，R 1表示2-氯且n为2; 当R2，R3，R4和R5代表氢时，R6不同于异丙基，R1表示2-氯，n是2; 或当R2，R3，R4和R5代表氢时，R1表示2-甲基，n表示2; 当R 1，R 2，R 3，R 4和R 5为氢且n表示2时，R 6与丙酰基不同。通式（I）的化合物可治疗用于治疗多巴胺能系统功能低下的疾病。