公开(公告)号：US09796761B2

公开(公告)日：2017-10-24

申请号：US13384031

申请日：2010-07-12

申请人： Hisashi Narimatsu ,  Jun Hirabayashi ,  Yuzuru Ikehara ,  Takashi Angata ,  Hiroyuki Kaji ,  Atsushi Kuno ,  Takashi Ohkura ,  Toshihide Shikanai ,  Maki Sogabe ,  Akira Togayachi ,  Makoto Ochou ,  Yasuhito Tanaka ,  Masashi Mizokami

发明人： Hisashi Narimatsu ,  Jun Hirabayashi ,  Yuzuru Ikehara ,  Takashi Angata ,  Hiroyuki Kaji ,  Atsushi Kuno ,  Takashi Ohkura ,  Toshihide Shikanai ,  Maki Sogabe ,  Akira Togayachi ,  Makoto Ochou ,  Yasuhito Tanaka ,  Masashi Mizokami

IPC分类号： C40B30/04 ,  C07K14/00 ,  C07K9/00 ,  C07K14/47 ,  G01N33/574

CPC分类号： C07K9/00 ,  C07K14/47 ,  G01N33/57438 ,  G01N33/57469 ,  G01N2400/02 ,  G01N2800/085

摘要： The present invention is directed to developing a glycan markers capable of detecting a hepatic disease, and more specifically to developing a glycan marker indicating a hepatic disease-state. Furthermore, the present invention is also directed to developing a glycan marker capable of distinguishing hepatic disease-states with the progress of hepatocarcinoma. The present inventors identified, among the serum glycoproteins, glycopeptides and glycoproteins in which a glycan structure specifically changes due to a hepatic diseases including hepatocarcinoma and provide these as novel glycan markers (glycopeptide and glycoprotein) specific to hepatic disease-states.

公开(公告)号：US20140323324A1

公开(公告)日：2014-10-30

申请号：US13994435

申请日：2011-12-16

申请人： Hisashi Narimatsu ,  Jun Hirabayashi ,  Atsushi Kuno ,  Hideki Matsuzaki ,  Yuzuru Ikehara ,  Hiromi Ito ,  Yasuhiro Hashimoto ,  Keiro Shirotani ,  Satoshi Futakawa ,  Hajime Arai ,  Masakazu Miyajima ,  Kazuo Fujihara

发明人： Hisashi Narimatsu ,  Jun Hirabayashi ,  Atsushi Kuno ,  Hideki Matsuzaki ,  Yuzuru Ikehara ,  Hiromi Ito ,  Yasuhiro Hashimoto ,  Keiro Shirotani ,  Satoshi Futakawa ,  Hajime Arai ,  Masakazu Miyajima ,  Kazuo Fujihara

IPC分类号： G01N33/68

CPC分类号： G01N33/6896 ,  G01N33/6842 ,  G01N2333/47 ,  G01N2333/4728 ,  G01N2400/40 ,  G01N2800/285 ,  H01J49/0036

摘要： The purpose of the present invention is to develop: a method for selectively separating a glycoprotein derived from the central nervous system from a body fluid or a central nervous system cell; and a method for searching for an index marker for central nervous system diseases, which utilizes the aforementioned method. A protein derived from the central nervous system, which occurs in a trace amount in a body fluid or a central nervous system cell, can be selectively enriched by a two-stage separation procedure comprising removing a glycoprotein having sialic acid at a non-reducing terminal thereof from the body fluid or the central nervous system cell and then separating a glycoprotein having N-acetylglucosamine at a non-reducing terminal thereof.

摘要翻译： 本发明的目的是开发：从体液或中枢神经系统细胞中选择性分离衍生自中枢神经系统的糖蛋白的方法; 以及利用上述方法搜索中枢神经系统疾病指标的方法。 可以通过两步分离方法选择性地富集来自中枢神经系统的蛋白质，其在体液或中枢神经系统细胞中发生微量的蛋白质，其包括在非还原末端除去具有唾液酸的糖蛋白 从体液或中枢神经系统细胞中分离，然后在其非还原末端分离具有N-乙酰葡糖胺的糖蛋白。

公开(公告)号：US08597576B2

公开(公告)日：2013-12-03

申请号：US13213596

申请日：2011-08-19

申请人： Jun Hirabayashi ,  Atsushi Kuno ,  Noboru Uchiyama

发明人： Jun Hirabayashi ,  Atsushi Kuno ,  Noboru Uchiyama

IPC分类号： G01N21/00

CPC分类号： G01N33/54373 ,  G01N21/648 ,  G01N33/54393 ,  G01N33/548

摘要： An analyzer of the present invention for analyzing a glycan or a complex glycan includes a substrate, a fluorescent labeling excitation means and a fluorescent intensity measurement means. The substrate comprises a rectangle photoconductive base plate coated by a compound containing an active group to fix protein by an amino group thereof, one and more open-topped reaction vessel formed on a surface of the base plate, and plural spots of glycan binding proteins arranged in a matrix and immobilized on the surface of the base plate in the reaction vessel. The fluorescent labeling excitation means which excites fluorescent label by generating evanescent-waves on the surface of the substrate comprises a pair of optical fibers arranged toward the both side end faces of the right and left of the substrate to introduce a light thereinto.

摘要翻译： 用于分析聚糖或复合聚糖的本发明的分析装置包括基板，荧光标记激励装置和荧光强度测量装置。 基板包括由含有活性基团的化合物包被以氨基固定蛋白质的矩形光导基板，在基板的表面上形成的一个或多个开放顶部的反应容器，以及布置的多个聚糖结合蛋白点 在基质中并固定在反应容器中的基板的表面上。 通过在衬底的表面上产生ev逝波来激发荧光标记的荧光标记激发装置包括一对光纤，其布置成朝向衬底的左右两侧端面以向其中引入光。

公开(公告)号：US20090041630A1

公开(公告)日：2009-02-12

申请号：US11917921

申请日：2006-06-14

申请人： Jun Hirabayashi ,  Atsushi Kuno ,  Noboru Uchiyama

发明人： Jun Hirabayashi ,  Atsushi Kuno ,  Noboru Uchiyama

IPC分类号： G01N21/64

CPC分类号： G01N33/54373 ,  G01N21/6428 ,  G01N21/648 ,  G01N33/54393 ,  G01N33/548

摘要： An analyzer for a glycan or a complex carbohydrate which comprises a substrate made of a photoconductive material having multiple types of glycan binding proteins provided and immobilized thereon a means of conducting light into the side edge face of the substrate and generating an evanescent wave on the substrate surface to thereby excite fluorescent labels, and a fluorescent intensity-measuring means of measuring the intensity of the fluorescence induced by the above means for each of the positions of the glycan binding proteins provided as described above.By using this analyzer, a glycan or a complex carbohydrate can be conveniently, quickly, highly sensitively and highly accurately analyzed.

摘要翻译： 用于聚糖或复合碳水化合物的分析仪，其包含由具有多种类型的聚糖结合蛋白的光电导材料制成的基底，所述基质提供并固定在其上，将光导入基片的侧边缘并在基底上产生ev逝波 表面，从而激发荧光标记;以及荧光强度测定单元，其通过上述方法对上述提供的聚糖结合蛋白的各个位置测定由上述方法诱导的荧光强度。 通过使用该分析仪，可以方便，快速，高灵敏度和高度准确地分析聚糖或复合碳水化合物。

公开(公告)号：US20070298485A1

公开(公告)日：2007-12-27

申请号：US10580279

申请日：2003-11-26

申请人： Keiichi Takagaki ,  Satoshi Kaneko ,  Atsushi Kuno

发明人： Keiichi Takagaki ,  Satoshi Kaneko ,  Atsushi Kuno

IPC分类号： C08B37/18 ,  C12S3/02

CPC分类号： C12P19/26 ,  C12P19/64

摘要： A method for collection of intact glycosaminoglycan from proteoglycan by cleaving a linkage region of core protein

摘要翻译： 通过切割核心蛋白的连锁区域，从蛋白聚糖中收集完整的糖胺聚糖的方法

公开(公告)号：US4698340A

公开(公告)日：1987-10-06

申请号：US753912

申请日：1985-07-11

申请人： Takao Takaya ,  Hisashi Takasugi ,  Atsushi Kuno ,  Yoshie Sugiyama

发明人： Takao Takaya ,  Hisashi Takasugi ,  Atsushi Kuno ,  Yoshie Sugiyama

IPC分类号： C07D213/50 ,  A61K31/505 ,  A61P9/00 ,  A61P25/28 ,  C07C205/56 ,  C07D213/55 ,  C07D239/20 ,  C07D239/26 ,  C07D239/28 ,  C07D239/30 ,  C07D239/34 ,  C07D239/42 ,  C07D333/00 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D409/04 ,  C07D491/04 ,  C07D491/048 ,  C07D491/052

CPC分类号： C07D239/26 ,  C07C205/45 ,  C07C205/56 ,  C07D239/20 ,  C07D239/30 ,  C07D239/42 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D409/04 ,  C07D491/04

摘要： The invention relates to pyrimidine derivatives and their pharmaceutically acceptable salts which are useful in the treatment of cerebrovascular diseases, to processes for preparation thereof and to the composition containing the same, said pyrimidine derivatives being represented by the following formula: ##STR1## wherein Ar, R.sup.1, R.sup.2 and R.sup.3 are as defined in the disclosure.

摘要翻译： 本发明涉及可用于治疗脑血管疾病的嘧啶衍生物及其药学上可接受的盐，其制备方法和含有该嘧啶衍生物的组合物，所述嘧啶衍生物由下式表示：其中Ar， R1，R2和R3如本公开中所定义。

公开(公告)号：US20070202535A1

公开(公告)日：2007-08-30

申请号：US10596692

申请日：2004-12-24

申请人： Jun Hirabayashi ,  Atsushi Kuno ,  Sachiko Nakamura ,  Noboru Uchiyama

发明人： Jun Hirabayashi ,  Atsushi Kuno ,  Sachiko Nakamura ,  Noboru Uchiyama

IPC分类号： G01N33/53 ,  C07K14/705

CPC分类号： G01N33/54393 ,  G01N33/543 ,  Y10S435/97

摘要： As a result of investigating the optimum conditions of methods for immobilizing proteins that interact with sugar chains onto a substrate, it was revealed that coating the surface of a slide glass with GTMS enables immobilization at a higher S/N ratio than conventionally possible. Moreover, by using a substrate to which a rubber with a number of holes was affixed to form a number of reaction vessels, and further by spotting lectins onto the substrate and washing with PBST, the weak interactions between sugar chains and lectins were successfully detected with improved sensitivity. In addition, by introducing an evanescent excitation-type scanner, it became possible to detect the interactions between lectins and sugar chains without washing away the probe solution.

摘要翻译： 通过研究将与糖链相互作用的蛋白质固定在基质上的最佳条件的结果，显示用GTMS涂覆载玻片的表面使得能够以比传统可能的更高的S / N比固定。 此外，通过使用固定有多个孔的橡胶的基板以形成多个反应容器，并且进一步通过将凝集素点样到基板上并用PBST洗涤，成功检测到糖链和凝集素之间的弱相互作用 提高灵敏度。 此外，通过引入ev逝激发型扫描仪，可以检测凝集素和糖链之间的相互作用而不洗掉探针溶液。

公开(公告)号：US4990507A

公开(公告)日：1991-02-05

申请号：US294743

申请日：1989-01-09

申请人： Takao Takaya ,  Hisashi Takasugi ,  Kimio Esumi ,  Atsushi Kuno ,  Hiroyoshi Sakai ,  Kazuhiro Maeda ,  Yoshie Sakamoto

发明人： Takao Takaya ,  Hisashi Takasugi ,  Kimio Esumi ,  Atsushi Kuno ,  Hiroyoshi Sakai ,  Kazuhiro Maeda ,  Yoshie Sakamoto

IPC分类号： C07D213/26 ,  C07D213/30 ,  C07D213/36 ,  C07D213/75 ,  C07D213/80 ,  C07D213/82 ,  C07D237/08 ,  C07D237/24 ,  C07D413/12 ,  C07D471/04 ,  C07D401/12 ,  A61K31/44

CPC分类号： C07D213/30 ,  C07D213/26 ,  C07D213/36 ,  C07D213/75 ,  C07D213/80 ,  C07D213/82 ,  C07D237/08 ,  C07D237/24 ,  C07D413/12 ,  C07D471/04

摘要： The invention relates to a pharmaceutical composition as a therapeutic agent for ischemic disease comprising a compound of the formula ##STR1## wherein R.sup.1 is carbamoyl substituted with morpholino (lower) alkyl, thiomorpholino(lower)alkyl or lower alkylamino(lower)alkyl; or ureido substituted with lower alkylamino(lower)alkyl; andR.sup.2 is phenyl substituted with nitro, andR.sup.4 is lower alkyl; orR.sup.2 is lower alkyl, andR.sup.4 is phenyl substituted with nitro;with proviso that R.sup.1 is carbamoyl substituted with thiomorpholino(lower)alkyl or lower alkylamino(lower)alkyl; or ureido substituted with lower alkylamino(lower)alkyl when R.sup.4 is lower alkyl; or its salt, as an active ingredient, in association with a pharmaceutically acceptable, substantially nontoxic carrier or excipient.

摘要翻译： 本发明涉及作为缺血性疾病治疗剂的药物组合物，其包含下式化合物其中R 1是被吗啉代（低级）烷基，硫代吗啉代（低级）烷基或低级烷基氨基（低级）烷基取代的氨基甲酰基） 或被低级烷基氨基（低级）烷基取代的脲基; R2是被硝基取代的苯基，R4是低级烷基; 或R 2为低级烷基，R 4为被硝基取代的苯基; 条件是R1是被硫代吗啉代（低级）烷基或低级烷基氨基（低级）烷基取代的氨基甲酰基; 或当R 4为低级烷基时被低级烷基氨基（低级）烷基取代的脲基; 或其盐作为活性成分，与药学上可接受的，基本上无毒的载体或赋形剂结合。

公开(公告)号：US4831030A

公开(公告)日：1989-05-16

申请号：US940923

申请日：1986-12-12

申请人： Hisashi Takasugi ,  Atsushi Kuno ,  Hiroyoshi Sakai ,  Yoshie Sugiyama ,  Takao Takaya

发明人： Hisashi Takasugi ,  Atsushi Kuno ,  Hiroyoshi Sakai ,  Yoshie Sugiyama ,  Takao Takaya

IPC分类号： C07D237/10 ,  A61K31/435 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/445 ,  A61K31/455 ,  A61K31/495 ,  A61K31/50 ,  A61K31/535 ,  A61K31/54 ,  A61P9/00 ,  A61P25/28 ,  C07D211/78 ,  C07D213/26 ,  C07D213/30 ,  C07D213/36 ,  C07D213/38 ,  C07D213/80 ,  C07D213/82 ,  C07D237/04 ,  C07D237/08 ,  C07D237/24 ,  C07D471/04

CPC分类号： C07D213/30 ,  C07D211/78 ,  C07D213/26 ,  C07D213/36 ,  C07D213/80 ,  C07D213/82 ,  C07D237/04 ,  C07D237/08 ,  C07D237/24 ,  C07D471/04

摘要： The invention relates to compounds for treatment of hypertension, and cardiovascular and cerebrovascular diseases, which compounds are of the formula: ##STR1## wherein R.sup.1 is piperazinyl(lower)alkyl, carbamoyl substituted with piperazinyl(lower)alkyl, or piperazinylcarbonyl, in each of which a piperazinyl group may be substituted with lower alkyl, andR.sup.3 is hydrogen or halogen;R.sup.2 is phenyl substituted with nitro, andR.sup.4 is lower alkyl or halo(lower)alkyl; orR.sup.2 is lower alkyl, andR.sup.4 is phenyl substitured with nitro;and a pharmaceutically acceptable salt thereof.

摘要翻译： 本发明涉及用于治疗高血压和心血管和脑血管疾病的化合物，其化合物具有下式：其中R 1是哌嗪基（低级）烷基，被哌嗪基（低级）烷基或哌嗪基羰基取代的氨基甲酰基， 哌嗪基可以被低级烷基取代，R3是氢或卤素; R2是被硝基取代的苯基，R4是低级烷基或卤代（低级）烷基; 或R2是低级烷基，R4是被硝基取代的苯基; 及其药学上可接受的盐。

公开(公告)号：US09696320B2

公开(公告)日：2017-07-04

申请号：US13823922

申请日：2011-09-09

申请人： Hisashi Narimatsu ,  Akira Togayachi ,  Yuzuru Ikehara ,  Hiroyuki Kaji ,  Atsushi Kuno ,  Takashi Ohkura ,  Hideki Matsuzaki ,  Yoshitoshi Hirao ,  Jun Iwaki ,  Minako Abe ,  Masaharu Nomura ,  Masayuki Noguchi

发明人： Hisashi Narimatsu ,  Akira Togayachi ,  Yuzuru Ikehara ,  Hiroyuki Kaji ,  Atsushi Kuno ,  Takashi Ohkura ,  Hideki Matsuzaki ,  Yoshitoshi Hirao ,  Jun Iwaki ,  Minako Abe ,  Masaharu Nomura ,  Masayuki Noguchi

IPC分类号： G01N33/574 ,  G01N33/68 ,  C07K14/47 ,  C07K16/28 ,  C07K16/30

CPC分类号： G01N33/6893 ,  C07K14/4748 ,  C07K16/28 ,  C07K16/3023 ,  G01N33/574 ,  G01N33/57423 ,  G01N2440/38

摘要： An object of the present invention is to develop and provide a lung cancer differential marker with which lung cancer can be diagnosed conveniently and highly sensitively without depending only on increase or decrease in protein expression level between cancer patients and healthy persons. Another object of the present invention is to develop and provide a glycan marker capable of distinguishing histological types of lung cancer. Of serum glycoproteins, glycopeptide and glycoprotein groups whose glycan structures were altered specifically in lung cancer cell culture supernatants were identified, and they are provided as lung cancer differential markers.