公开(公告)号：US4564493A

公开(公告)日：1986-01-14

申请号：US602097

申请日：1984-04-20

申请人： Tsuneo Shintani ,  Soichi Kojima ,  Masuo Goto

发明人： Tsuneo Shintani ,  Soichi Kojima ,  Masuo Goto

IPC分类号： B22D41/52 ,  B28B1/24 ,  C04B35/101 ,  B28B3/22

CPC分类号： C04B35/101 ,  B22D41/52 ,  B28B1/24

摘要： A composition of flake graphite, binder clay and a refractory material is extruded from an auger machine into a mold to form a cylindrical graphitic casting nozzle brick. The mold includes a coaxial core terminating short of an extrusion die of the auger machine, so that the graphitic casting nozzle brick as extruded has a longitudinal bore with one end closed, with transverse holes being subsequently defined through the nozzle brick across the bore adjacent to the closed end. As an alternative, a coaxial core may be connected to an extrusion screw of the auger machine to define an axial through bore in the casting nozzle brick as the latter is extruded.

摘要翻译： 将片状石墨，粘结剂粘土和耐火材料的组合物从螺旋钻机挤出到模具中以形成圆柱形石墨铸造喷嘴砖。 该模具包括一个终止于螺旋钻机的挤出模头的同轴芯，使得挤出的石墨铸造喷嘴砖具有纵向孔，其一端封闭，随后通过喷嘴砖将横向孔定义成穿过相邻的孔 封闭的一面。 作为替代方案，同轴芯可以连接到螺旋钻机的挤压螺杆，以在铸造喷嘴砖中限定出轴向通孔，因为后者被挤出。

公开(公告)号：US20130244253A1

公开(公告)日：2013-09-19

申请号：US13819979

申请日：2011-08-30

申请人： Soichi Kojima ,  Mitsuko Hara ,  Takehisa Matsumoto ,  Daisuke Takaya

发明人： Soichi Kojima ,  Mitsuko Hara ,  Takehisa Matsumoto ,  Daisuke Takaya

IPC分类号： C12N9/99 ,  C07K16/28 ,  C07K16/40

CPC分类号： C12N9/99 ,  C07K16/2863 ,  C07K16/40 ,  C07K2317/34 ,  C07K2317/76 ,  C12Q1/37 ,  G01N2500/02

摘要： An object is to provide a compound capable of inhibiting activation of TGF-β receptors due to HCV, and a screening method for the compound. It has been found that a HCV-derived NS3 protease binds to type I TGF-β receptor, and this binding results in activation of TGF-β receptors. Moreover, binding sites between the NS3 protease and type I TGF-β receptor were identified, and it has been found that antibodies recognizing these binding sites inhibit activation of TGF-β receptors due to NS3 protease. Furthermore, it has been also found that screening for a compound capable of inhibiting activation of TGF-β receptors can be performed by using the inhibition of the binding between NS3 protease and type I TGF-β receptor or the like as an index.

摘要翻译： 目的是提供能够抑制由于HCV引起的TGF-β受体活化的化合物和该化合物的筛选方法。 已经发现，HCV衍生的NS3蛋白酶结合I型TGF-β受体，并且该结合导致TGF-β受体的活化。 此外，鉴定了NS3蛋白酶和I型TGF-β受体之间的结合位点，并且已经发现识别这些结合位点的抗体由于NS3蛋白酶而抑制TGF-β受体的活化。 此外，还发现可以通过使用抑制NS3蛋白酶和I型TGF-β受体等之间的结合作为指标来进行能够抑制TGF-β受体活化的化合物的筛选。

公开(公告)号：US20130045977A1

公开(公告)日：2013-02-21

申请号：US13579843

申请日：2011-02-17

申请人： Hideaki Kakeya ,  Akira Hattori ,  Yasuaki Takasu ,  Nobutaka Fujii ,  Shinya Oishi ,  Soichi Kojima ,  Mitsuko Hara

发明人： Hideaki Kakeya ,  Akira Hattori ,  Yasuaki Takasu ,  Nobutaka Fujii ,  Shinya Oishi ,  Soichi Kojima ,  Mitsuko Hara

IPC分类号： A61K31/445 ,  C07D401/12 ,  A61P25/00 ,  C07D413/12 ,  A61K31/5377 ,  A61P35/00 ,  C07D211/32 ,  A61K31/4545

CPC分类号： C07D295/104 ,  C07D211/28 ,  C07D295/18 ,  C07D405/12

摘要： The present invention provides a compound represented by the following formula (I) or a physiologically acceptable salt thereof, and use thereof for the prophylaxis or treatment of TGF-β-related diseases: wherein Y is a hydrogen atom and the like; R2 is and the like; R3 is —NR8—R9— and the like; R4, R5, R6 and R7 are the same or different and each is a hydrogen atom and the like; and X is and the like.

摘要翻译： 本发明提供由下式（I）表示的化合物或其生理学上可接受的盐，及其用于预防或治疗TGF-β相关疾病的用途：其中Y为氢原子等; R2是等等; R3是-NR8-R9-等; R4，R5，R6和R7相同或不同，各自为氢原子等; X等。

公开(公告)号：US08198412B2

公开(公告)日：2012-06-12

申请号：US12856195

申请日：2010-08-13

申请人： Soichi Kojima ,  Naoshi Dohmae ,  Wakako Kondo

发明人： Soichi Kojima ,  Naoshi Dohmae ,  Wakako Kondo

IPC分类号： C07K16/00 ,  A61K39/395

CPC分类号： G01N33/6893

摘要： It is an object of the present invention to provide antibodies capable of detecting an active TGF-β generation reaction that is specific to pathogenesis, tissues, or isoforms. The present invention provides antibodies against an LAP fragment (or latent TGF-β) generated as a result of generation of active form of human TGF-β1, human TGF-β2 and human TGF-β3. The antibodies are able to specifically recognize respective cutting edges within protease cleavage sites existing in the region from the amino acid residue glycine at position 51 to the amino acid residue arginine at position 110 of human TGF-β1, and corresponding regions of human TGF-β2 and human TGF-β3.

摘要翻译： 本发明的目的是提供能够检测活性TGF-β的抗体。 对发病机制，组织或同种型具有特异性的代谢反应。 本发明提供针对由生成人TGF-β1，人TGF-β2和人TGF-β1活性形式产生的LAP片段（或潜在TGF-β）的抗体。 抗体能够特异性地识别存在于人TGF-β1的氨基酸残基甘氨酸位置51的氨基酸残基甘氨酸和人TGF-β1的相应区域的氨基酸残基精氨酸的蛋白酶切割位点内的相应切割边缘 - ＆bgr; 2和人类TGF-和bgr; 3。

公开(公告)号：US07803553B2

公开(公告)日：2010-09-28

申请号：US10570606

申请日：2004-09-03

申请人： Soichi Kojima ,  Naoshi Dohmae ,  Wakako Kondo

发明人： Soichi Kojima ,  Naoshi Dohmae ,  Wakako Kondo

IPC分类号： G01N33/53

CPC分类号： G01N33/6893

摘要： It is an object of the present invention to provide antibodies capable of detecting an active TGF-β generation reaction that is specific to pathogenesis, tissues, or isoforms. The present invention provides antibodies against an LAP fragment (or latent TGF-β) generated as a result of generation of active form of human TGF-β1, human TGOF-β2 and human TGF-β3. The antibodies are able to specifically recognize respective cutting edges within protease cleavage sites existing in the region from the amino acid residue glycine at position 51 to the amino acid residue arginine at position 110 of human TGF-β1, and corresponding regions of human TGF-β2 and human TGF-β3.

摘要翻译： 本发明的目的是提供能够检测活性TGF-β的抗体。 对发病机制，组织或同种型具有特异性的代谢反应。 本发明提供针对由生成人TGF-β1，人TGF-β2和人TGF-β1活性形式产生的LAP片段（或潜在TGF-β）的抗体。 抗体能够特异性地识别存在于人TGF-β1的氨基酸残基甘氨酸位置51的氨基酸残基甘氨酸和人TGF-β1的相应区域的氨基酸残基精氨酸的蛋白酶切割位点内的相应切割边缘 - ＆bgr; 2和人类TGF-和bgr; 3。

公开(公告)号：US08951521B2

公开(公告)日：2015-02-10

申请号：US13819979

申请日：2011-08-30

申请人： Soichi Kojima ,  Mitsuko Hara ,  Takehisa Matsumoto ,  Daisuke Takaya

发明人： Soichi Kojima ,  Mitsuko Hara ,  Takehisa Matsumoto ,  Daisuke Takaya

IPC分类号： A61K39/00 ,  A61K39/395 ,  C12N9/99 ,  C07K16/28 ,  C07K16/40 ,  C12Q1/37

CPC分类号： C12N9/99 ,  C07K16/2863 ,  C07K16/40 ,  C07K2317/34 ,  C07K2317/76 ,  C12Q1/37 ,  G01N2500/02

摘要： An object is to provide a compound capable of inhibiting activation of TGF-β receptors due to HCV, and a screening method for the compound. It has been found that a HCV-derived NS3 protease binds to type I TGF-β receptor, and this binding results in activation of TGF-β receptors. Moreover, binding sites between the NS3 protease and type I TGF-β receptor were identified, and it has been found that antibodies recognizing these binding sites inhibit activation of TGF-β receptors due to NS3 protease. Furthermore, it has been also found that screening for a compound capable of inhibiting activation of TGF-β receptors can be performed by using the inhibition of the binding between NS3 protease and type I TGF-β receptor or the like as an index.

摘要翻译： 目的是提供能够抑制TGF-β的活化的化合物。 由于HCV引起的受体，以及该化合物的筛选方法。 已经发现，HCV衍生的NS3蛋白酶结合I型TGF- 受体，这种结合导致TGF-β的活化; 受体。 此外，NS3蛋白酶和I型TGF-和bgr之间的结合位点 受体被鉴定，并且已经发现识别这些结合位点的抗体抑制TGF-β的活化。 由NS3蛋白酶引起的受体。 此外，还发现筛选能够抑制TGF-β的活化的化合物 受体可通过使用抑制NS3蛋白酶和I型TGF-βb结合来进行; 受体等作为指标。

公开(公告)号：US08772297B2

公开(公告)日：2014-07-08

申请号：US13579843

申请日：2011-02-17

申请人： Hideaki Kakeya ,  Akira Hattori ,  Yasuaki Takasu ,  Nobutaka Fujii ,  Shinya Oishi ,  Soichi Kojima ,  Mitsuko Hara

发明人： Hideaki Kakeya ,  Akira Hattori ,  Yasuaki Takasu ,  Nobutaka Fujii ,  Shinya Oishi ,  Soichi Kojima ,  Mitsuko Hara

IPC分类号： A61K31/495 ,  C07D295/104

CPC分类号： C07D295/104 ,  C07D211/28 ,  C07D295/18 ,  C07D405/12

摘要： The present invention provides a compound represented by the following formula (I) or a physiologically acceptable salt thereof, and use thereof for the prophylaxis or treatment of TGF-β-related diseases: wherein Y is a hydrogen atom and the like; R2 is and the like; R3 is —NR8—R9— and the like; R4, R5, R6 and R7 are the same or different and each is a hydrogen atom and the like; and X is and the like.

摘要翻译： 本发明提供由下式（I）表示的化合物或其生理学上可接受的盐，及其用于预防或治疗TGF-β相关疾病的用途：其中Y为氢原子等; R2是等等; R3是-NR8-R9-等; R4，R5，R6和R7相同或不同，各自为氢原子等; X等。

公开(公告)号：US20080038748A1

公开(公告)日：2008-02-14

申请号：US10570606

申请日：2004-09-03

申请人： Soichi Kojima ,  Naoshi Dohmae ,  Wakako Kondo

发明人： Soichi Kojima ,  Naoshi Dohmae ,  Wakako Kondo

IPC分类号： C07K16/24 ,  G01N33/53

CPC分类号： G01N33/6893

摘要： It is an object of the present invention to provide antibodies capable of detecting an active TGF-β generation reaction that is specific to pathogenesis, tissues, or isoforms. The present invention provides antibodies against an LAP fragment (or latent TGF-β) generated as a result of generation of active form of human TGF-β1, human TGOF-β2 and human TGF-β3. The antibodies are able to specifically recognize respective cutting edges within protease cleavage sites existing in the region from the amino acid residue glycine at position 51 to the amino acid residue arginine at position 110 of human TGF-β1, and corresponding regions of human TGF-β2 and human TGF-β3.

摘要翻译： 本发明的目的是提供能够检测对发病机理，组织或同种型特异的活性TGF-β产生反应的抗体。 本发明提供针对由生成人TGF-β1，人TGOF-β2和人TGF-β3的活性形式产生的LAP片段（或潜在TGF-β）的抗体。 抗体能够特异性地识别存在于人类TGF-β1的氨基酸残基甘氨酸到人TGF-β1的110位氨基酸残基精氨酸的区域内存在的蛋白酶切割位点内的相应切割边缘，以及人TGF-β2的相应区域 和人TGF-β3。