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CYTOKINE STORM INHIBITOR

外国特許コード F160008833
整理番号 (S2015-0245-N0)
掲載日 2016年8月10日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2015JP085693
国際公開番号 WO 2016104436
国際出願日 平成27年12月21日(2015.12.21)
国際公開日 平成28年6月30日(2016.6.30)
優先権データ
  • 特願2014-258546 (2014.12.22) JP
  • 特願2015-154972 (2015.8.5) JP
発明の名称 (英語) CYTOKINE STORM INHIBITOR
発明の概要(英語) 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).
従来技術、競合技術の概要(英語) 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.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY
  • 発明者(英語)
  • NISHIBORI, Masahiro
  • MORI, Shuji
  • WAKE, Hidenori
国際特許分類(IPC)
指定国 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

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