TOP > 外国特許検索 > NOVEL THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE

NOVEL THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE

外国特許コード F160008797
整理番号 (S2015-0060-N0)
掲載日 2016年8月4日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2015JP081417
国際公開番号 WO 2016072522
国際出願日 平成27年11月6日(2015.11.6)
国際公開日 平成28年5月12日(2016.5.12)
優先権データ
  • 20140-226236 JP
  • 特願2015-196282 (2015.10.1) JP
発明の名称 (英語) NOVEL THERAPEUTIC AGENT FOR ALZHEIMER'S DISEASE
発明の概要(英語) The purpose of the present invention is to provide an agent for the prevention and/or treatment of Alzheimer's disease, the agent having a novel mechanism of action and reduced side effects. A polyphenol derivative having heightened liposolubility due to the introduction of at least one liposoluble group selected from the group consisting of linear saturated hydrocarbon groups, linear unsaturated hydrocarbon groups, cyclic saturated hydrocarbon groups, cyclic unsaturated hydrocarbon groups, aromatic hydrocarbon groups, liposoluble vitamin residues, and stearoyl residues exhibits an effect for potentiating the activity of neprilysin and is useful as an agent for the prevention and/or treatment of Alzheimer's disease.
従来技術、競合技術の概要(英語) BACKGROUND ART
Older apprenticeship AD dementia is a main factor for the progressive neurodegenerative disease, clinical symptoms of the accumulation of extracellular amyloid β peptide until→intracellular tau aggregation, neurodegenerative→accumulation, neuronal cell death (amyloid hypothesis) that follow the pathological cascade. Therefore, from the accumulation of A β AD is believed to begin, the underlying A β for the treatment to inhibit the production of, promote degradation of, the suppression of aggregation, aggregation A β in the brain from the removal of the deposits has to be removed and, for the development of such an anti-scale agent A β world are a research has been competed.
Therapeutic agent for AD, such as Aricept there exists a number of drug, both only has effectively alleviates the disease condition, the underlying therapeutic agent may be not. On the other hand, the conventional A β metabolism studies of β and γ secretase related to producing system has been provided for analysis, drug discovery AD of these enzymes in the development of inhibitors targeting preceded by, a plurality of medicament clinical trial was performed. However, side-effects such as a hard with one another in the current situation. The point of action of other aggregated deposits removal of inhibition agents (A β vaccine therapy) and also, to clinical trials proceeds is, in either case side effects are developed for composing the stop.
A β in the brain for the decomposition of the system, referred to as Neutral peptidase responsible for degradation of the enzyme have been reported (non-patent document 1, 2). Present in a variety of tissues of the animal Neutral neutral endopeptidase which is a kind of, a catalytic site to the extracellular domain of the membrane-bound enzyme. In the in vitro experiments, enkephalin, substance P, atrial natriuretic peptide (ANP), gastrin-releasing peptide (GRP), endothelin and the like Neutral substrate may become known.
Normal aging brain A β amyloid AD or accumulation observed in the brain and the progression of the pathological condition associated with a decrease in neprilysin level results have been reported. Normal mice model mouse hippocampus and cerebral cortex of AD with age and the expression level is significantly reduced. In recent years, for a human is similarly revealed a lowered, neprilysin level A β 42 level and lowering of the insoluble fractions have been reported to correlate inversely with.
Lowering of the neprilysin level also AD in the brain, in a plurality of independent research group reported is consistent results. Temporal lobe and the hippocampus of AD in a pre-stage, 50% expression amount and protein amount Neutral was reduced nearly is known. Amyloid pathology are resistant to the cerebellum is the amount of expression of the hippocampus and the medial temporal lobe Neutral high compared, not found reduced expression of Neutral. On the other hand, autopsy brain amyloid pathology that is advanced further lowers the neprilysin level anymore, significant reduction of the control group to 70% is shown.
Decomposition system with attention paid to the underlying AD AD therapeutic agent is expected as a therapeutic agent is, at present, using Neutral AD gene gene therapy attempts performed using model mice of a stage in which the only.
Polyphenols, antioxidant action, cholesterol lowering action, antibacterial action and the like, has a positive influence on health maintenance is generally well known. In addition, the catechins of the polyphenols in tea-derived component is a report that works on AD (non-patent document 3-5). 1 A type of polyphenol, having the following structure
(-) - Epigallocatechin having gallate (EGCg) - 3-O - cells in the nervous system to increase the activity of neutral endopeptidase enzyme is reported (non-patent document 6-9), in these experiments neutral endopeptidase general artificial substrate is used in the, which will actually not clear whether the enzyme has been applied. An alkyl chain EGCg is added to enhance the fat-soluble (hydrophobic), the utilization rate in vivo (intestinal absorption efficiency and migration in the brain) reported increased derivatives (patent document 1, non-patent document 10). Poly phenol such as ginkgo biloba is included in a placement flavones inhibition and cell death protective effect A β have been reported (non-patent document 11, 12). In many plant polyphenols may be included in the aggregation-suppressing effect of apigenin A β have been reported (non-patent document 13, 14). Also included in the strawberry A β such as suppression of the production kaempferol, A β-inhibition, cell death protective effect has been known. However, any polyphenol Neutral for showing the relationship between the article but, in addition, the polyphenol can be derivatized a better anti-AD effect can be obtained not describe or suggest.
The amyloid precursor protein (APP) an enzyme that metabolizes as α, β and γ secretase have been known. Β and γ secretase A β is produced by, on the other hand, in the interior of the A β APP α secretase is cut. A β α secretase APP is metabolized and is not produced, with attention paid to increasing the activity of α-secretase AD therapeutics may also be expected.
  • 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
  • NAGASAKI UNIVERSITY
  • 発明者(英語)
  • IWATA NOBUHISA
  • SHIROTANI KEIRO
  • ASAI MASASHI
  • TANAKA TAKASHI
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
上記の特許・技術に関心のある方は、下記問い合わせ先にご相談下さい。

PAGE TOP

close
close
close
close
close
close