Top > Search of International Patents > CYTOKINE STORM INHIBITOR

CYTOKINE STORM INHIBITOR

Foreign code F160008833
File No. (S2015-0245-N0)
Posted date Aug 10, 2016
Country WIPO
International application number 2015JP085693
International publication number WO 2016104436
Date of international filing Dec 21, 2015
Date of international publication Jun 30, 2016
Priority data
  • P2014-258546 (Dec 22, 2014) JP
  • P2015-154972 (Aug 5, 2015) JP
Title CYTOKINE STORM INHIBITOR
Abstract The present invention addresses the problem of providing a novel cytokine storm inhibitor. The present invention is a cytokine storm inhibitor that uses HRG as an active ingredient, based on the discovery that HRG acts to inhibit a plurality of types of cytokines. HRG also acts to inhibit inflammatory cytokines and anti-inflammatory cytokines. The present invention is also a drug for preventing or treating systemic inflammatory response syndrome (SIRS), the drug including this cytokine storm inhibitor having HRG as an active ingredient. According to this cytokine storm inhibitor, it is possible to suppress the elevation, in the blood or lung tissue, of levels of two or more cytokines selected from a plurality of types of cytokines, e.g., IL-6, TNF-α, IL-10, KC (CXCL1), MCP-1 (CCL2), MIG (CXCL9), and MIP-1 alpha (CCL3).
Outline of related art and contending technology BACKGROUND ART
Cytokines, inflammatory responses of the proteinaceous factor involved in an immune response a general term, contained several hundred types of one or more factors. Cytokines, the individual has a very colorful activity profile, in concert with a good balance in their interaction with the biological function is maintained, for the regulation. The cytokines, particularly inflammatory disease, autoimmune disease, the pathology of neurodegenerative disease mediators play an important role in the formation as is known.
Is abnormally increased cytokine concentrations in blood state, or cytokine storm, referred to as high cytokine hypoxemia. Such as for example infections caused by drug administration, blood cytokine (IL-1, IL-6, such as TNF-α) an abnormal increase in occurs. For example, Ebola hemorrhagic fever, after a high degree of surgical invasion, such as systemic inflammatory response syndrome (systemic inflammatory response syndrome after drug administration: hereinafter, simply referred to as' SIRS '.) Observed before a stage of diseases such as a symptom. SIRS is, increased rate of respiration, such as the production of liver acute phase protein which is known to exhibit enhanced. Use of an experimental animal model for a disease state SIRS as a result of analyzing, having an activity of inflammatory cytokines causes inflammation (inflammatory cytokines) the significant increase in FAK in the blood has been confirmed. The severity of the disease state is further SIRS, as well as increasing the concentration of inflammatory cytokines, inflammation, anti-inflammatory cytokines to suppress an immune response also increases and the concentration, the immune response generated is considered to be a failure. Cytokine storm is, disseminated intravascular coagulation syndrome SIRS (DIC) from, to the stage to multi-organ failure are also confirmed.
In recent years, TNF-α and interleukin -6 (IL-6) with an antibody that targets the molecule pharmaceutical success has been reported, anti-cytokine therapy is being slit open a new era. Antibody pharmaceuticals is, the activity of the target cytokines or their receptors and block the specific. However, anti-inflammatory cytokines and inflammatory cytokines such as SIRS simultaneously for complicated reaction conditions, it is difficult to control by the antibody pharmaceuticals described above, which may control a plurality of types of cytokine is a need for the development of a medicament. CD61 Sub-unit of a cell surface molecule antibody binds to the protein, may control a plurality of types of cytokines have been reported (Patent Document 1) but, may control the medicament is a plurality of types of cytokines has not been the practical use.
Is HRG(Histidine-rich glycoprotein), 1972 year to about 80kDa molecular weight identified by Heimburger et al (1972) plasma protein. A total of 507 amino acids, wherein the histidine 66 and histidine-containing proteins present in high, mainly synthesized in the liver, as high as about 100-150μg/ml in human plasma at a concentration believed to be present. HRG is, adjustment of the fibrinolytic system of coagulation line involved in the regulation of angiogenesis is known (non-patent document 1). Further, the polypeptide of HRG method of inhibiting angiogenesis by, HRG polypeptide, the receptor and antibodies that bind the polypeptide HRG, HRG-deficient plasma and polynucleotides, encoding a polypeptide HRG including vector and a host cell, the product and a pharmaceutical formulation comprising the disclosed (patent document 2). In addition, relates to the field of angiogenesis, including subfragments of the central region of the HRG derived from anti-angiogenic activity of the substantially pure polypeptide is disclosure relating to the use of continuous (Patent Document 3). In addition, activation of neutrophils with HRG is report control function will be (patent document 4).
However, a plurality of types of cytokines by HRG with regard to the control, has not been reported.
Scope of claims (In Japanese)[請求項1]
ヒスチジンリッチ糖タンパク質を有効成分として含有する、サイトカインストーム抑制剤。
[請求項2]
サイトカインストーム抑制剤により、血中及び/又は肺組織中のIL-6、TNF-α、IL-10、KC(CXCL1)、MCP-1(CCL2)、MIG(CXCL9)及びMIP-1 alpha(CCL3)から選択される2種以上のサイトカインが抑制される、請求項1に記載のサイトカインストーム抑制剤。
[請求項3]
ヒスチジンリッチ糖タンパク質が、ヒト血液成分又は遺伝子組換えの手法により動物細胞により産生された粗ヒスチジンリッチ糖タンパク質を、アフィニティーゲルクロマトグラフィーを用いて精製して得たタンパク質である、請求項1又は2に記載のサイトカインストーム抑制剤。
[請求項4]
ヒスチジンリッチ糖タンパク質が、遺伝子組換えの手法により作製されたヒスチジンリッチ糖タンパク質である、請求項3に記載のサイトカインストーム抑制剤。
[請求項5]
ヒスチジンリッチ糖タンパク質を有効成分として含有するサイトカインストーム抑制剤の作製方法として、ヒト血液成分又は動物細胞により産生された粗ヒスチジンリッチ糖タンパク質を、アフィニティーゲルクロマトグラフィーを用いて精製し、有効成分としてのヒスチジンリッチ糖タンパク質を調製する工程を含むことを特徴とする、サイトカインストーム抑制剤の作製方法。
[請求項6]
請求項1~4のいずれか1に記載のサイトカインストーム抑制剤を含む、全身性炎症反応症候群(SIRS)の予防剤又は治療剤。
[請求項7]
請求項1~4のいずれか1に記載のサイトカインストーム抑制剤を用いることを特徴とする、血中及び/又は肺組織中のIL-6、TNF-α、IL-10、KC(CXCL1)、MCP-1(CCL2)、MIG(CXCL9)及びMIP-1 alpha(CCL3)から選択される2種以上のサイトカインを抑制するサイトカインストーム抑制方法。
[請求項8]
請求項1~4のいずれか1に記載のサイトカインストーム抑制剤を用いることを特徴とする、全身性炎症反応症候群(SIRS)の予防又は治療方法。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY
  • Inventor
  • NISHIBORI, Masahiro
  • MORI, Shuji
  • WAKE, Hidenori
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG

PAGE TOP

close
close
close
close
close
close