公开(公告)号：US08263347B2

公开(公告)日：2012-09-11

申请号：US12738684

申请日：2008-10-20

Applicant: Hirohito Tsubouchi ,  Hirofumi Uto ,  Takeshi Okanoue ,  Yo-ichi Ishida ,  Yuko Sato ,  Masayuki Sudo

Inventor： Hirohito Tsubouchi ,  Hirofumi Uto ,  Takeshi Okanoue ,  Yo-ichi Ishida ,  Yuko Sato ,  Masayuki Sudo

IPC: G01N33/53

CPC classification number: G01N33/6893 ,  G01N2333/8139 ,  G01N2800/085

Abstract: Disclosed are: a marker for the diagnosis of a liver disease, which can determine the disease in a simple manner; an antibody directed against the marker; a diagnostic agent; a diagnosis method; and a method for marker detection in blood or serum. Proteome analysis revealed that quantities of the full-length kininogen and three partial peptides thereof (sequence A: position-440 to position-456, sequence B: position-439 to position-456, and sequence C: position-438 to position-456) in sera of patients with non-alcoholic fatty liver disease are significantly different from those in sera of healthy individuals; and a diagnostic agent and a detecting method for the non-alcoholic fatty liver disease that can be conveniently used for medical examination are established. The use of a combination of a kininogen-based marker and a C4-based marker (the full length sequence or partial peptides thereof) enables identification of chronic hepatitis and an asymptomatic virus carrier, as well as non-alcoholic fatty liver disease.

Abstract translation: 公开了一种用于诊断肝脏疾病的标志物，其可以以简单的方式确定疾病; 针对标记的抗体; 诊断剂; 诊断方法; 以及血液或血清中标记物检测的方法。 蛋白质组分析显示，全长激肽原及其三个部分肽（序列A：位置440至位置-456，序列B：位置-439至位置-456，序列C：位置-438至位置-456） ）与非酒精性脂肪性肝病患者的血清显着不同于健康人血清; 并建立了可以方便地用于体格检查的非酒精性脂肪肝疾病的诊断剂和检测方法。 使用基于激肽原的标记物和基于C4的标记物（其全长序列或其部分肽）的组合能够鉴定慢性肝炎和无症状病毒载体以及非酒精性脂肪肝疾病。

公开(公告)号：US20110288164A1

公开(公告)日：2011-11-24

申请号：US13204219

申请日：2011-08-05

Applicant: Masahiko TAKESHITA ,  Hirohito TSUBOUCHI ,  Hirofumi UTO ,  Hiroaki KATAOKA ,  Takanori KAI ,  Hideaki HIRABARU ,  Miho SAKAI ,  Ena AKAMATSU

Inventor： Masahiko TAKESHITA ,  Hirohito TSUBOUCHI ,  Hirofumi UTO ,  Hiroaki KATAOKA ,  Takanori KAI ,  Hideaki HIRABARU ,  Miho SAKAI ,  Ena AKAMATSU

IPC: A61K31/353 ,  A61P31/14

CPC classification number: A61K31/74 ,  A61K36/45 ,  C07D311/62

Abstract: This invention provides an agent for inhibiting production of hepatitis C virus with notable anti-HCV activity and without side-effects. The agent comprises a proanthocyanidin polymer composition illustrated in the following the general formula (1), wherein R1 is hydrogen or hydroxyl, R2 is hydroxyl, R3 is hydrogen when R1 is either hydrogen or hydroxyl, but R3 is possibly hydroxyl when R1 is either hydrogen or hydroxyl to the extent that both R1 and R3 being hydroxyl is at most 40 percents in the proanthocyanidin polymer composition said units of flavan-3-ol being bonded each other in any one of three patterns as follows; (i) a bond between carbon at the position 4 and carbon at the position 8, (ii) a bond between carbon at the position 4 and carbon at the position 6, (iii) a bond between carbon at the position 4 and carbon at the position 8, and between carbon, at the position 2 and oxygen at the position 7.

Abstract translation: 本发明提供用于抑制具有显着的抗HCV活性并且没有副作用的丙型肝炎病毒生产的药剂。 该试剂包含如下通式（1）所示的原花青素聚合物组合物，其中R 1为氢或羟基，R 2为羟基，R 3为氢时，R 1为氢或羟基，但当R 1为氢时，R 3为羟基 或羟基，其中R 1和R 3为羟基在原花色素聚合物组合物中至多为40％的程度，所述黄烷-3-醇单元以如下三种模式中的任一种彼此结合; （i）位置4的碳和位置8的碳之间的键，（ii）位置4的碳与位置6的碳之间的键;（iii）位置4的碳与碳之间的键 位置8，碳之间，位置2和位置7处的氧。

公开(公告)号：US20110129859A1

公开(公告)日：2011-06-02

申请号：US12738684

申请日：2008-10-20

Applicant: Hirohito Tsubouchi ,  Hirofumi Uto ,  Takeshi Okanoue ,  Yo-ichi Ishida ,  Yuko Sato ,  Masayuki Sudo

Inventor： Hirohito Tsubouchi ,  Hirofumi Uto ,  Takeshi Okanoue ,  Yo-ichi Ishida ,  Yuko Sato ,  Masayuki Sudo

IPC: G01N33/53 ,  C07K7/08 ,  C07K14/435 ,  C07K16/18

CPC classification number: G01N33/6893 ,  G01N2333/8139 ,  G01N2800/085

Abstract: Disclosed are: a marker for the diagnosis of a liver disease, which can determine the disease in a simple manner; an antibody directed against the marker; a diagnostic agent; a diagnosis method; and a method for marker detection in blood or serum. Proteome analysis revealed that quantities of the full-length kininogen and three partial peptides thereof (sequence A: position-440 to position-456, sequence B: position-439 to position-456, and sequence C: position-438 to position-456) in sera of patients with non-alcoholic fatty liver disease are significantly different from those in sera of healthy individuals; and a diagnostic agent and a detecting method for the non-alcoholic fatty liver disease that can be conveniently used for medical examination are established. The use of a combination of a kininogen-based marker and a C4-based marker (the full length sequence or partial peptides thereof) enables identification of chronic hepatitis and an asymptomatic virus carrier, as well as non-alcoholic fatty liver disease.

Abstract translation: 公开了：用于诊断肝脏疾病的标志物，其可以以简单的方式确定疾病; 针对标记的抗体; 诊断剂; 诊断方法; 以及血液或血清中标记物检测的方法。 蛋白质组分析显示，全长激肽原及其三个部分肽（序列A：位置440至位置-456，序列B：位置-439至位置-456，序列C：位置-438至位置-456） ）与非酒精性脂肪性肝病患者的血清显着不同于健康人血清; 建立了可以方便地用于体格检查的非酒精性脂肪肝疾病的诊断剂和检测方法。 使用基于激肽原的标记物和基于C4的标记物（其全长序列或其部分肽）的组合能够鉴定慢性肝炎和无症状病毒载体以及非酒精性脂肪肝疾病。

公开(公告)号：US08846751B2

公开(公告)日：2014-09-30

申请号：US13204219

申请日：2011-08-05

Applicant: Masahiko Takeshita ,  Hirohito Tsubouchi ,  Hirofumi Uto ,  Hiroaki Kataoka ,  Takanori Kai ,  Hideaki Hirabaru ,  Miho Sakai ,  Ena Akamatsu

Inventor： Masahiko Takeshita ,  Hirohito Tsubouchi ,  Hirofumi Uto ,  Hiroaki Kataoka ,  Takanori Kai ,  Hideaki Hirabaru ,  Miho Sakai ,  Ena Akamatsu

IPC: A01N43/16 ,  C07D311/62 ,  A61K31/74 ,  A61K36/45

CPC classification number: A61K31/74 ,  A61K36/45 ,  C07D311/62

Abstract: This invention provides an agent for inhibiting production of hepatitis C virus with notable anti-HCV activity and without side-effects. The agent comprises a proanthocyanidin polymer composition illustrated in the following the general formula (1), wherein R1 is hydrogen or hydroxyl, R2 is hydroxyl, R3 is hydrogen when R1 is either hydrogen or hydroxyl, but R3 is possibly hydroxyl when R1 is either hydrogen or hydroxyl to the extent that both R1 and R3 being hydroxyl is at most 40 percents in the proanthocyanidin polymer composition said units of flavan-3-ol being bonded each other in any one of three patterns as follows; (i) a bond between carbon at the position 4 and carbon at the position 8, (ii) a bond between carbon at the position 4 and carbon at the position 6, (iii) a bond between carbon at the position 4 and carbon at the position 8, and between carbon, at the position 2 and oxygen at the position 7.

Abstract translation: 本发明提供用于抑制具有显着的抗HCV活性并且没有副作用的丙型肝炎病毒生产的药剂。 该试剂包含如下通式（1）所示的原花青素聚合物组合物，其中R 1为氢或羟基，R 2为羟基，R 3为氢时，R 1为氢或羟基，但当R 1为氢时，R 3为羟基 或羟基，其中R 1和R 3为羟基在原花色素聚合物组合物中至多为40％的程度，所述黄烷-3-醇单元以如下三种模式中的任一种彼此结合; （i）位置4的碳和位置8的碳之间的键，（ii）位置4的碳与位置6的碳之间的键;（iii）位置4的碳与碳之间的键 位置8，碳之间，位置2和位置7处的氧。

公开(公告)号：US20100055065A1

公开(公告)日：2010-03-04

申请号：US12546281

申请日：2009-08-24

Applicant: Masahiko TAKESHITA ,  Hirohito TSUBOUCHI ,  Hirofumi UTO ,  Hiroaki KATAOKA ,  Takanori KAI ,  Hideaki HIRABARU ,  Miho SAKAI ,  Ena AKAMATSU

Inventor： Masahiko TAKESHITA ,  Hirohito TSUBOUCHI ,  Hirofumi UTO ,  Hiroaki KATAOKA ,  Takanori KAI ,  Hideaki HIRABARU ,  Miho SAKAI ,  Ena AKAMATSU

IPC: A61K31/74

CPC classification number: A61K31/74 ,  A61K36/45 ,  C07D311/62

Abstract: This invention provides an agent for inhibiting production of hepatitis C virus with notable anti-HCV activity and without side-effects. The agent comprises a proanthocyanidin polymer composition illustrated in the following the general formula (1), wherein R1 is hydrogen or hydroxyl, R2 is hydroxyl, R3 is hydrogen when R1 is either hydrogen or hydroxyl, but R3 is possibly hydroxyl when R1 is either hydrogen or hydroxyl to the extent that both R1 and R3 being hydroxyl is at most 40 percents in the proanthocyanidin polymer composition said units of flavan-3-ol being bonded each other in any one of three patterns as follows; (i) a bond between carbon at the position 4 and carbon at the position 8, (ii) a bond between carbon at the position 4 and carbon at the position 6, (iii) a bond between carbon at the position 4 and carbon at the position 8, and between carbon at the position 2 and oxygen at the position 7.

Abstract translation: 本发明提供用于抑制具有显着的抗HCV活性并且没有副作用的丙型肝炎病毒生产的药剂。 该试剂包含如下通式（1）所示的原花青素聚合物组合物，其中R 1为氢或羟基，R 2为羟基，R 3为氢时，R 1为氢或羟基，但当R 1为氢时，R 3为羟基 或羟基，其中R 1和R 3为羟基在原花色素聚合物组合物中至多为40％的程度，所述黄烷-3-醇单元以如下三种模式中的任一种彼此结合; （i）位置4的碳和位置8的碳之间的键，（ii）位置4的碳与位置6的碳之间的键;（iii）位置4的碳与碳之间的键 位置8，位置2的碳和位置7的氧之间。