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    Method of measuring the activity of lipid-modified enzyme
    1.
    发明授权
    Method of measuring the activity of lipid-modified enzyme 有权
    测定脂质修饰酶活性的方法

    公开(公告)号：US08318449B2

    公开(公告)日：2012-11-27

    申请号：US12619457

    申请日：2009-11-16

    申请人： Naoyuki Fukuchi

    发明人： Naoyuki Fukuchi

    IPC分类号： C12Q1/60

    CPC分类号： G01N33/573 ,  C12Q1/34 ,  C12Q1/42 ,  C12Q1/44 ,  C12Q1/48 ,  G01N33/5432 ,  G01N2500/00

    摘要： It is intended to provide an assay method whereby the activity of a lipid-modifying enzyme can be conveniently measured over a wide range and a drug capable of controlling a lipid-modifying enzyme with the use of this assay method. The above problem can be solved by, for example, a method of measuring the activity of a lipid-modifying enzyme which comprises the steps of (I) preparing a lipid micelle containing a biotinylated lipid and a substrate for the lipid-modifying enzyme; (II) bringing the lipid micelle prepared in the above step (I) into contact with the lipid-modifying enzyme; and (III) evaluating the activity of the lipid-modifying enzyme by applying an evaluation method using the proximity effect to the product obtained in the above step (II).

    摘要翻译： 旨在提供一种测定方法，其中可以在宽范围内方便地测量脂质修饰酶的活性，并且使用能够使用该测定方法控制脂质修饰酶的药物。 上述问题可以通过例如测定脂质修饰酶的活性的方法来解决，该方法包括以下步骤：（I）制备含有生物素化脂质和脂质修饰酶底物的脂质胶束; （II）使上述步骤（I）中制备的脂质胶束与脂质修饰酶接触; 和（III）通过使用对上述步骤（II）中获得的产物的邻近效应的评价方法评估脂质修饰酶的活性。

    Acylamide compounds having secretagogue or inducer activity of adiponectin
    2.
    发明授权
    Acylamide compounds having secretagogue or inducer activity of adiponectin 失效
    具有促分泌素或脂联素诱导活性的酰胺化合物

    公开(公告)号：US07732637B2

    公开(公告)日：2010-06-08

    申请号：US11835029

    申请日：2007-08-07

    申请人： Katsumi Maezono ,  Toshihiko Yoshimura ,  Nozomu Ishida ,  Naoyuki Fukuchi ,  Toshihiro Hatanaka ,  Osamu Ikehara ,  Yayoi Kawato ,  Hideyuki Tanaka

    发明人： Katsumi Maezono ,  Toshihiko Yoshimura ,  Nozomu Ishida ,  Naoyuki Fukuchi ,  Toshihiro Hatanaka ,  Osamu Ikehara ,  Yayoi Kawato ,  Hideyuki Tanaka

    IPC分类号： C07C229/06 ,  A61K31/20

    CPC分类号： C07C233/47 ,  A23L33/10 ,  C07C323/59

    摘要： The present invention provides an acylamide compound of the following formula (1), prodrugs thereof, or pharmaceutically acceptable salts thereof; and an adiponectin inducer or secretagogue, therapeutic agent of metabolic syndromes, therapeutic agent of hypoadiponectinemia, therapeutic agent of hyperlipemia, preventive/therapeutic agent of diabetes, improving agent of impaired glucose tolerance, improving agent of insulin resistance, enhancing agent of insulin sensitivity, therapeutic agent of hypertension, preventive/therapeutic agent of vascular disorders, an anti-inflammatory agent, therapeutic agent of hepatic inflammation, therapeutic agent of fatty liver, therapeutic agent of hepatic fibrosis, therapeutic agent of liver cirrhosis, preventive/therapeutic agent of non-alcoholic/nonviral steatohepatitis (NASH) or non-alcoholic/nonviral fatty liver disease (NAFLD), or therapeutic agent of obesity, each of which has the above compounds as an active ingredient.

    摘要翻译： 本发明提供下式（1）的酰胺化合物，其前体药物或其药学上可接受的盐; 和脂联素诱导剂或促分泌素，代谢综合征的治疗剂，低脂联素血症的治疗剂，高脂血症的治疗剂，糖尿病的预防/治疗剂，葡萄糖耐量降低的改善剂，胰岛素抵抗的改善剂，胰岛素敏感性的增强剂，治疗 高血压药物，血管疾病的预防/治疗剂，抗炎剂，肝脏炎症治疗剂，脂肪肝治疗剂，肝纤维化治疗剂，肝硬化治疗剂，非酒精性预防/治疗剂 /非病毒性脂肪性肝炎（NASH）或非酒精性/非病毒性脂肪性肝病（NAFLD）或肥胖症治疗剂，其各自具有上述化合物作为活性成分。

    Substance with antithrombotic activity and method for detecting glycokallidin
    5.
    发明授权
    Substance with antithrombotic activity and method for detecting glycokallidin 失效
    具有抗血栓活性的物质和检测糖调素的方法

    公开(公告)号：US06878811B1

    公开(公告)日：2005-04-12

    申请号：US09673245

    申请日：1999-01-13

    申请人： Naoyuki Fukuchi ,  Fumie Futaki ,  Morikazu Kito ,  Koichi Ishii ,  Akiko Tanaka

    发明人： Naoyuki Fukuchi ,  Fumie Futaki ,  Morikazu Kito ,  Koichi Ishii ,  Akiko Tanaka

    IPC分类号： C07K14/705 ,  C07K14/755 ,  G01N33/86 ,  C12P21/08 ,  G01N33/53

    CPC分类号： C07K14/705 ,  C07K14/755 ,  C07K2317/52 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/86 ,  G01N2333/755

    摘要： A method for conveniently detecting binding between the von Willebrand factor and glycoprotein Ib and a means to be used therein. The von Willebrand factor fixed in a reactor immobilized in a reaction vessel in the presence of bottrocetin is bound to a chimeric protein constructed by fusing the carboxyl terminal of a partial protein containing the von Willebrand factor-binding site of glycoprotein Ib with the amino terminal of the Fc region of an immunoglobulin molecule. Then the Fc region of the above immunoglobulin molecule is detected to thereby detect the binding between the von Willebrand factor and the glycoprotein Ib or inhibition of this binding.

    摘要翻译： 一种方便检测血管性血友病因子与糖蛋白Ⅰb之间的结合的方法及其中使用的方法。 固定在反应容器中的存在于布可菌素的反应器中的血管性血友病因子结合于通过将含有糖蛋白1b的血管性血友病变因子结合位点的部分蛋白的羧基末端与羧基末端相连的氨基末端 免疫球蛋白分子的Fc区。 然后检测上述免疫球蛋白分子的Fc区，从而检测血管性血友病因子与糖蛋白Ib之间的结合或抑制该结合。

    ACYLAMIDE COMPOUNDS HAVING SECRETAGOGUE OR INDUCER ACTIVITY OF ADIPONECTIN
    8.
    发明申请
    ACYLAMIDE COMPOUNDS HAVING SECRETAGOGUE OR INDUCER ACTIVITY OF ADIPONECTIN 失效
    具有ADIPONECTIN的秘密活性或诱导活性的酰亚胺化合物

    公开(公告)号：US20070282002A1

    公开(公告)日：2007-12-06

    申请号：US11835029

    申请日：2007-08-07

    申请人： Katsumi MAEZONO ,  Toshihiko Yoshimura ,  Nozomu Ishida ,  Naoyuki Fukuchi ,  Toshihiro Hatanaka ,  Osamu Ikehara ,  Yayoi Kawato ,  Hideyuki Tanaka

    发明人： Katsumi MAEZONO ,  Toshihiko Yoshimura ,  Nozomu Ishida ,  Naoyuki Fukuchi ,  Toshihiro Hatanaka ,  Osamu Ikehara ,  Yayoi Kawato ,  Hideyuki Tanaka

    IPC分类号： A61K31/198 ,  C07C235/12

    CPC分类号： C07C233/47 ,  A23L33/10 ,  C07C323/59

    摘要： The present invention provides an acylamide compound of the following formula (1), prodrugs thereof, or pharmaceutically acceptable salts thereof; and an adiponectin inducer or secretagogue, therapeutic agent of metabolic syndromes, therapeutic agent of hypoadiponectinemia, therapeutic agent of hyperlipemia, preventive/therapeutic agent of diabetes, improving agent of impaired glucose tolerance, improving agent of insulin resistance, enhancing agent of insulin sensitivity, therapeutic agent of hypertension, preventive/therapeutic agent of vascular disorders, an anti-inflammatory agent, therapeutic agent of hepatic inflammation, therapeutic agent of fatty liver, therapeutic agent of hepatic fibrosis, therapeutic agent of liver cirrhosis, preventive/therapeutic agent of non-alcoholic/nonviral steatohepatitis (NASH) or non-alcoholic/nonviral fatty liver disease (NAFLD), or therapeutic agent of obesity, each of which has the above compounds as an active ingredient.

    摘要翻译： 本发明提供下式（1）的酰胺化合物，其前体药物或其药学上可接受的盐; 和脂联素诱导剂或促分泌素，代谢综合征的治疗剂，低脂联素血症的治疗剂，高脂血症的治疗剂，糖尿病的预防/治疗剂，葡萄糖耐量降低的改善剂，胰岛素抵抗的改善剂，胰岛素敏感性的增强剂，治疗 高血压药物，血管疾病的预防/治疗剂，抗炎剂，肝脏炎症治疗剂，脂肪肝治疗剂，肝纤维化治疗剂，肝硬化治疗剂，非酒精性预防/治疗剂 /非病毒性脂肪性肝炎（NASH）或非酒精性/非病毒性脂肪性肝病（NAFLD）或肥胖症治疗剂，其各自具有上述化合物作为活性成分。

    Inhibitors of the GPIb—vWF interaction, their preparation and use
    9.
    发明授权
    Inhibitors of the GPIb—vWF interaction, their preparation and use 有权
    GPIb-vWF相互作用的抑制剂，其制备和使用

    公开(公告)号：US07235558B2

    公开(公告)日：2007-06-26

    申请号：US10454939

    申请日：2003-06-04

    申请人： Otmar Klingler ,  Melitta Just ,  Kuniya Sakurai ,  Naoyuki Fukuchi

    发明人： Otmar Klingler ,  Melitta Just ,  Kuniya Sakurai ,  Naoyuki Fukuchi

    IPC分类号： C07D215/46

    CPC分类号： C07D401/12 ,  C07D215/48 ,  C07D401/14 ,  C07D417/12

    摘要： The present invention relates to compounds of the formula I, in which R1, R2, A, B, D, F, n, m and o have the meanings indicated herein. The compounds of the formula I are valuable pharmacologically active compounds. They are reversible inhibitors of the interaction between the plasma protein von Willebrand factor (vWF) and the blood platelet receptor glycoprotein Ib-IX-V complex (GPIb). They exhibit an antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of atherothrombotic diseases

    摘要翻译： 本发明涉及式Ⅰ化合物，其中R1，R2，A，B，D，F，n，m和o具有本文所述的含义。 式I的化合物是有价值的药理活性化合物。 它们是血浆蛋白血管性血友病因子（vWF）和血小板受体糖蛋白Ib-IX-V复合物（GPIb）之间相互作用的可逆抑制剂。 它们表现出抗血栓形成的作用，例如适用于治疗和预防动脉粥样硬化血栓形成疾病

    Protein having antithrombotic activity and method for producing the same
    10.
    发明授权
    Protein having antithrombotic activity and method for producing the same 失效
    具有抗血栓形成活性的蛋白质及其制造方法

    公开(公告)号：US06710031B2

    公开(公告)日：2004-03-23

    申请号：US09969763

    申请日：2001-10-04

    申请人： Naoyuki Fukuchi ,  Morikazu Kito ,  Takashi Kayahara ,  Fumie Futaki ,  Kohki Ishikawa ,  Eiichiro Suzuki ,  Keiko Gondoh ,  Nobuhisa Shimba ,  Naoyuki Yamada

    发明人： Naoyuki Fukuchi ,  Morikazu Kito ,  Takashi Kayahara ,  Fumie Futaki ,  Kohki Ishikawa ,  Eiichiro Suzuki ,  Keiko Gondoh ,  Nobuhisa Shimba ,  Naoyuki Yamada

    IPC分类号： A61K3846

    CPC分类号： C07K14/46 ,  C07K14/745

    摘要： A method for producing a protein having an antithrombotic activity, which comprises replacing, in a protein that has an amino acid sequence having a homology of not less than 30% to the amino acid sequence of SEQ ID NO: 1 and forms a higher order structure composed of a first &bgr; strand (&bgr;1), a first &agr; helix (&agr;1), a second &agr; helix (&agr;2), a second &bgr; strand (&bgr;2), a loop, a third &bgr; strand (&bgr;3), a fourth &bgr; strand (&bgr;4) and a fifth &bgr; strand (&bgr;5) in this order from the amino terminus, at least one amino acid residue in a region from &agr;2 to &bgr;2 and/or a region from &bgr;3 to &bgr;4 so that electric charge of the amino acid residue is changed towards positive direction.

    摘要翻译： 一种具有抗血栓形成活性的蛋白质的制造方法，其特征在于，具有与SEQ ID NO：1的氨基酸序列具有不小于30％的同源性的氨基酸序列的蛋白质，并形成高级结构 由第一β链（β1），第一α螺旋（alpha1），第二α螺旋（α2），第二β链（β2），环，第三β链（β3），第四条β链 β4）和第五个β链（β5），从氨基末端起始，α2至β2区域和/或β3至β4区域中的至少一个氨基酸残基，使得氨基酸残基的电荷为 转向正向。