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DEVICE FOR PROPHYLAXIS AND TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS

Foreign code F120006398
File No. 10011
Posted date Apr 3, 2012
Country WIPO
International application number 2011JP078506
International publication number WO 2012077774
Date of international filing Dec 9, 2011
Date of international publication Jun 14, 2012
Priority data
  • P2010-276407 (Dec 10, 2010) JP
Title DEVICE FOR PROPHYLAXIS AND TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS
Abstract [Problem] The purpose of the present invention is to provide a device for the prophylaxis and treatment of systemic lupus erythematosus, a method for use as a biomarker of systemic lupus erythematosus, and a method for determining systemic lupus erythematosus.
[Solution] The prophylaxis/treatment of systemic lupus erythematosus is characterized by reducing the concentration of Hsp90 in the blood, the serum, or the blood plasma of a subject by using a substance capable of removing Hsp90. The method for use as a biomarker of systemic lupus erythematosus is characterized by using Hsp90 in the blood, the serum, or the blood plasma of a subject as a biomarker. The method for determining systemic lupus erythematosus is characterized by comparing and evaluating the concentration of Hsp90 in the blood, the serum, or the blood plasma of a subject with/against that of a normal control.
Outline of related art and contending technology BACKGROUND ART
Systemic lupus erythematosus (systemic lupus erythematosus; SLE) (hereinafter, simply referred to as' SLE ' also displayed.) Is, anti-nuclear antibody or anti-DNA antibody or the immune complex in various organs, tissue induced by the deposition of inflammatory reactions may occur in a systemic autoimmune disease. There are a variety of clinical symptoms, the heat generation, anemia, thrombocytopenia, facial butterfly erythema, the erythema-like rash, the multi-joint pain, arthritis and serosa, kidney condition, diarrhea, cardiovascular symptoms are seen.
SLE is not yet clear the cause of the details of, in addition to genetic factors, ultraviolet, viral infection, trauma, surgery, pregnancy, childbirth, and environmental factors such as drug treatments involving thought to develop. In addition, in the SLE, interferon α peak value in the serum of exacerbations of the disease state is considered to be one of the factors.
Diagnosis of SLE, butterfly erythema cheek 1, 2 occurs at the site of the other distinctive rash, sensitivity to light 3, 4 in the mouth ulcers, arthritis 5, 6 lung, heart, other organs in the vicinity of the accumulated water (serosa flame), renal dysfunction 7, 8 decrease in white cell count, decrease in the number of red blood cells with a hemolytic anemia, decreased platelet count, 9 such as the brain and neuronal dysfunction, anti-nuclear antibody reaction in the blood test 10 positive, 11 stranded DNA antibody blood test for anti-2 positive, 11 of items, corresponding to the two or more of the 4 is performed by it can be confirmed. However, these diagnostic items include, severe symptoms of the heart and therefore, a more powerful early diagnosis in order to also possible, new diagnostic items have been required.
In addition, the treatment of SLE, mild symptoms in the case of non-steroidal anti-inflammatory agents such as aspirin is used, in the case of severe symptoms, at the present, such as prednisolone and adrenal cortical steroid drug is mainly used. Corticosteroid agents, anti-inflammatory effect and because of the immune, inflammation and improve an organ lesions in SLE and, in the production of autoantibodies or autoreactive lymphocytes by inhibiting the function of, a treatment for SLE are believed to be effective. However, a corticosteroid agent, which also reduces the function of protection against infection of the human on the other, high blood pressure, heart failure, diabetes, peptic ulcer disease, renal failure, osteoporosis and the like are deteriorated in some cases, their use requires sufficient attention should be paid. In addition, a corticosteroid drug over a long period, by intravenous injection or oral use, high blood pressure, increase in blood glucose level, cataracts, osteoporosis, hemorrhagic side effects such as the stomach is also a problem that occurs. Therefore, a corticosteroid agent other than the development of therapeutic agents is performed in SLE. For example, to Patent Document 1, a family of enzymes the inhibitory capacity of PDE4, 9 and 2 of adenine and optionally at the position being derived from the N (6) - substituted adenine compound, can be used in the treatment of SLE has been disclosed. However, such compounds, or a combination of drugs and corticosteroids assumed. In such a situation, fewer side-effects, a new method of treatment of SLE has been demanded.
In addition, heat shock protein (HSP) is, by heat shock protein to increase expression, radiation other than heat, may also react to the stress such as malnutrition known to increase. As a function of the heat shock protein, and the various proteins in the cell form a complex, thereby stabilizing the protein to function properly and function as molecular chaperones, in particular heat shock protein (Hsp90) is of the 90 client proteins such as protein kinase or a steroid hormone receptors which play an important role in cell proliferation and differentiation of signal transduction molecules are known to often. In addition, the heat shock protein, forming a complex with the peptide and, when exposed to stress from infected cells or tumor cells is released outside the cells, and contributes to the immune response has also been known.
In addition, the non-patent document 1, interferon α interferon γ and Hsp90 can be activated and, by comprising the inhibitor of Hsp90, and interferons α antiviral effect of interferon γ suppresses been described. In addition, in Patent Document 2, Tumor Necrosis Factor α (Tumor Necrosis Factor Hsp90 α: TNF α) and interleukin 6 (IL-6) to activate and is described, in its claim 21, systemic lupus erythematosus (SLE) Hsp90 inhibitors such as by administering to the patient, a method of reducing TNF α and IL-6 has been described. In addition, by the present inventors is the non-patent document 2, a complex with its own DNA Hsp90 (Hsp90 - self-DNA complex) is formed, and to suppress the decomposition of the self-DNA, and, as human DNA-plasma cells and efficiently incorporated into the dendritic cells, dendritic cells may be transformed with DNA in which the self-cell-like can be localized in the endosome initial, dendritic cell-like human traits can facilitate the production of interferon-α has been suggested. Further, in Non-Patent Document 3, in the peripheral blood mononuclear cells in patients with SLE, and increased expression of Hsp90 that has been described. However, Hsp90 is not a secreted protein, its concentration in the serum of SLE patients is significantly increased not contemplated that, in addition, also not known.
Scope of claims (In Japanese)請求の範囲 [請求項1]
Hsp90の除去手段を備えたことを特徴とする全身性エリテマトーデスの予防・治療装置。

[請求項2]
Hsp90の除去手段が、Hsp90の除去物質を含むことを特徴とする請求項1に記載の予防・治療装置。

[請求項3]
Hsp90の除去物質が、固相担体に担持されていることを特徴とする請求項1又は2に記載の予防・治療装置。

[請求項4]
血液中、血清中又は血漿中のHsp90を、全身性エリテマトーデスのバイオマーカーとして使用する方法。

[請求項5]
以下の(A)及び(B)の工程を備えることを特徴とする全身性エリテマトーデスの判定方法;
(A)被検体の血液中、血清中又は血漿中のHsp90濃度をインビトロで測定する工程;
(B)前記工程(A)で測定したHsp90濃度を、正常対照の血液中、血清中又は血漿中のHsp90濃度と比較・評価する工程;

[請求項6]
以下の(C)又は(D)の工程をさらに備えることを特徴とする請求項5に記載の判定方法;
(C)前記工程(A)で測定したHsp90濃度が、正常対照の血液中、血清中又は血漿中のHsp90濃度よりも高い場合に、前記被検体を全身性エリテマトーデスと評価する工程;
(D)前記工程(A)で測定したHsp90濃度が、正常対照の血液中、血清中又は血漿中のHsp90濃度よりも高い程度を、前記被検体の全身性エリテマトーデスの病状の重さの程度と評価する工程;

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • SAPPORO MEDICAL UNIVERSITY
  • Inventor
  • TAMURA Yasuaki
  • SATOH Noriyuki
  • TORIGOE Toshihiko
  • SAITOH Keita
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH 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 IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU RW 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 MD 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 ML MR NE SN TD TG

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