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METHOD FOR PREVENTION AND TREATMENT OF METABOLIC SYNDROME THROUGH THE INHIBITION OF PSGL-1

Foreign code F100002336
Posted date Dec 14, 2010
Country WIPO
International application number 2009JP059045
International publication number WO 2009139459
Date of international filing May 15, 2009
Date of international publication Nov 19, 2009
Priority data
  • P2008-128086 (May 15, 2008) JP
Title METHOD FOR PREVENTION AND TREATMENT OF METABOLIC SYNDROME THROUGH THE INHIBITION OF PSGL-1
Abstract Disclosed is a prophylactic and/or therapeutic agent which can exhibit an effect by itself on the prevention and/or treatment of a basic condition of a lifestyle-related disease such as metabolic syndrome and type-2 diabetes. Also disclosed is a method for the screening of the prophylactic and/or therapeutic agent. Specifically disclosed is a prophylactic and/or therapeutic agent for metabolic diseases, which comprises an inhibitor of PSGL-1 as an active ingredient.
Outline of related art and contending technology BACKGROUND ART
In advanced countries, life-style related diseases, in particular the metabolic and significantly increased in recent years of affected individuals, are a critical issue in the medical. In a patient with metabolic syndrome, visceral fat type obesity, hyperglycemia, hypertension, hyperlipidemia and symptoms such as heavy product, the product of the severity of the condition, such as myocardial infarction or cerebral artery disease is likely to develop is high. The diagnostic criteria for metabolic syndrome is not unified worldwide, for example in Japan, visceral fat type obesity and essential item, further high blood pressure, abnormal serum lipid levels of hyperglycemia and 2 corresponds to the two or more of the metabolic syndrome is diagnosed.
Of the metabolic syndrome is epidemic in recent years, largely for lack of exercise and, as an objective the treatment heretofore dietary and exercise regimens have been emphasized. However, these therapies are, a fundamental improvement such the patient's own life style often force, therefore it is difficult to realize in many cases. On the other hand, the major metabolic syndrome hypertension is a disease state, for each of the serum hyperglycemia and dyslipidemia and drug therapy has been attempted, for example, in the treatment of low HDL - high triglyceride/fibrate or the statin drug is; altered glucose metabolism is sulfonylurea agents, rapid-acting insulin secretagogues, or insulin resistance-improving agent α - glucosidase inhibitors; hypertension an angiotensin-converting enzyme inhibitor or adrenaline α receptor antagonist and the like are used. However, these drug therapies are, medical costs are expensive and not necessarily therapeutic efficacy such as to ensure that there are problems. In addition, visceral fat type obesity drug therapy includes, central appetite suppressants and indirectly by the prevention or treatment is being performed only.
Metabolic syndrome or type 2 diabetes including in the development of life-style related diseases, the importance of insulin resistance has been widely recognized. Insulin resistance is a, skeletal muscle cells, liver cells, such as in fat cells, by a reduction in insulin sensitivity, insulin secretion is maintained but, refers to a decrease in its action. Insulin resistance and hyperinsulinemia, glucose intolerance and then, further induces abnormal lipid metabolism and hypertension is considered to be a (non-patent document 1). Is a development mechanism of insulin resistance are not always fully apparent not, provided by the conventional nonalcoholic state and lack of exercise and increased visceral fat accumulation has been regarded as important. Further, in recent years, obesity and insulin resistance is interposed between the inflammation have been revealed and, the size of the fat cells, necrosis and coronary surrounding it is macrophage accumulation, which leads to inflammation and insulin resistance is thus spread.
Is PSGL-1, leukocytes and vascular endothelial cells and cells involved in the adhesion of the surface of a molecule cloned as a ligand for a selectin P- membrane protein (patent document 1, non-patent document 2). Is PSGL-1, and disulfide bond 220kDa, Most blood leukocytes (for example, neutrophils, monocytes, macrophages, B a subset of cells, and all T cells) expressing PSGL-1 is known. Inflammation is extremely important in the migration of leukocytes to the injured tissue in the course of and invasion of a wide variety of cell adhesion molecule is responsible, in the early stages of inflammation observed is a phenomenon called rolling, specific to them Selectin sugar chain interacting with the ligands (for example P- the interaction of selectins PSGL-1) known to be performed via the (non-patent document 3 and 4). However, type 2 diabetes or metabolic syndrome including lifestyle-related disease in the pathogenesis of, PSGL-1 plays an important role has not been known hitherto.
Scope of claims (In Japanese)請求の範囲 [請求項1]
 PSGL-1に対する阻害物質を有効成分として含有する、代謝性疾患の予防及び/又は治療剤。

[請求項2]
 代謝性疾患が、メタボリックシンドローム、2型糖尿病、耐糖能異常、肥満症又は脂質異常症である、請求項1記載の剤。

[請求項3]
 PSGL-1に対する阻害物質が、PSGL-1に対する特異的中和抗体、或いはPSGL-1の発現を特異的に阻害可能なアンチセンス核酸若しくは小分子量干渉RNA、又はこれらを哺乳動物細胞内において発現可能な発現ベクターである、請求項1記載の剤。

[請求項4]
 以下の工程を含む、代謝性疾患を予防又は治療し得る物質のスクリーニング方法:
(I)被験物質がPSGL-1の機能を阻害するか検定すること、及び
(II)PSGL-1の機能を阻害した被験物質を代謝性疾患を予防又は治療し得る物質として選択すること。

[請求項5]
 代謝性疾患が、メタボリックシンドローム、2型糖尿病、耐糖能異常、肥満症又は脂質異常症である、請求項4記載の方法。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • National University Corporation Okayama University
  • Inventor
  • SHIKATA, Kenichi
  • MAKINO, Hirofumi
  • SATO, Chikage
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 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 PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: 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 SE SI SK TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

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