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AGENT FOR PREVENTING, AMELIORATING OR TREATING ACANTHOTIC DISEASE AND/OR ACANTHOTIC SYMPTOM

Foreign code F190009759
File No. (S2017-0737-N0)
Posted date May 7, 2019
Country WIPO
International application number 2018JP019345
International publication number WO 2018212341
Date of international filing May 18, 2018
Date of international publication Nov 22, 2018
Priority data
  • P2017-100149 (May 19, 2017) JP
Title AGENT FOR PREVENTING, AMELIORATING OR TREATING ACANTHOTIC DISEASE AND/OR ACANTHOTIC SYMPTOM
Abstract The present invention addresses the problem of providing an active ingredient having an effect of preventing, ameliorating or treating an acanthotic disease and/or an acanthotic symptom. This problem is solved by an agent for preventing, ameliorating or treating an acanthotic disease and/or an acanthotic symptom, said agent comprising at least one member selected from the group consisting of phospholipase D and an expression cassette thereof.
Outline of related art and contending technology BACKGROUND ART
Lipid homeostasis of the skin is considered very important in a biological component. For example, the epidermis of the skin surface in contact with the external world (keratinocytes) ceramide of keratinocytes (a kind of sphingolipids) of the formed layer, such as a pathogen or evaporation of water from the body of the body from entering with a hotspot. Keratinocyte differentiation and proliferation of the cycle is broken, the disturbance of the barrier of the skin, including diseases such as psoriasis skin thickening, such as the stratum corneum ichthyosis severe deficiency disease, atopic dermatitis and further, such as allergic diseases leads to contact dermatitis.
Sphingolipids in addition, the living body is present in the lipid having a glycerol backbone. Phospholipid glycerophospholipides 1 of one of the main components and the cell membrane, its metabolic abnormality is involved in various disease. Glycerophospholipids is, in a manner that the coupling of the glycerol backbone sn-1 ester-bond addition (acyl-type), an ether-bond (alkyl type) or a vinyl ether-bond is present (alkenyl-type) (Fig. 1). These phospholipid, lysophosphatidic acid is metabolized to a plurality of enzyme, via a plurality of specific receptors, cancer invasion, a fertilized egg landing, angiogenesis, involved in the formation of hair. Alkyl-lysophospholipids metabolites, platelet activating factor, via the receptor has the effect of bronchoconstriction. Alkenyl phospholipid is, also referred to as a plasmalogen, phospholipid in the living body 2 which occupies about the interrupt, especially cranial nerve, muscle, lymphocytes, macrophages and a high content of the. Biosynthesis of plasmalogen the failure, fatal neurological disease is known to exhibit a (non-patent document 1), its function will be often unknown.
In recent years, a phospholipid phospholipase A2 (PLA2) the decomposition enzyme is associated with various biological response has been reported (Non-Patent Document 2). PLA2 Is, phospholipid fatty acid degradation of enzyme lysophospholipid and generic groups, lipid mediators (local transiently acidic is, bioactivity of the bioactive lipid and are collectively referred to) starting the production of the enzyme and at the same time, the fatty acid metabolism and the regulation of energy balance, membrane enzyme involved in reconstruction. PLA2 In the genome of a mammal having a name corresponding to the 30 code and one or more molecules, these molecules can be controlled by a variety of biological response is apparent.
PLA2 Of 1 type (sPLA2-IIF) is PLA2G2F, certain lysophospholipid by production, epidermal thickening disease have been reported to be involved in the (non-patent document 3, Fig. 2). The mechanism is as follows. Is PLA2G2F, increases in psoriasis Th17 cytokines (IL-22) derived by the expression, secreted from the skin keratinocytes 1-(1Z-octadecenyl) -2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine( phosphatidylethanolamine-type plasmalogen, P-PE(18:0/22:6) ) to decompose, plasmalogen 1-O-1'-(Z) -octadecenyl-2-hydroxy-sn-glycero-3-phosphoethanolamine( LPEAT-type lysophosphatidyletanolamine, (18:0) P-LPE) is generated. P-LPE is generated, acting on the keratinocytes exacerbate inflammation and skin thickening by, epidermal thickening property involved in the disease progression.
Scope of claims (In Japanese)請求の範囲 [請求項1]
ホスホリパーゼD及びその発現カセットからなる群より選択される少なくとも1種を含有する、表皮肥厚症状の予防又は改善剤。

[請求項2]
前記ホスホリパーゼDがリゾリン脂質を基質として活性を示すホスホリパーゼDである、請求項1に記載の剤。

[請求項3]
前記ホスホリパーゼDがアルケニル型リゾリン脂質を基質として活性を示すホスホリパーゼDである、請求項1又は2に記載の剤。

[請求項4]
前記ホスホリパーゼDがアルケニル型リゾホスファチジルエタノールアミンを基質として活性を示すホスホリパーゼDである、請求項1又は2に記載の剤。

[請求項5]
前記ホスホリパーゼDがThermocrispum属細菌由来ホスホリパーゼDである、請求項1~4のいずれかに記載の剤。

[請求項6]
前記ホスホリパーゼDが下記(a)~(e)の特性:
(a)分子量が28~38 kDaであること、
(b)至適温度が45~53℃であること、
(c)至適pHが3.5~10.5であること、
(d)カルシウムイオン又はアルミニウムイオンにより酵素活性が増加すること、及び(e)マグネシウムイオンにより酵素活性が減少すること、
からなる群より選択される少なくとも1種を満たすホスホリパーゼDである、請求項1~5のいずれかに記載の剤。

[請求項7]
前記ホスホリパーゼDがThermocrispum sp.のRD004668株由来ホスホリパーゼDである、請求項1~6のいずれかに記載の剤。

[請求項8]
前記ホスホリパーゼDが下記(i)又は(ii)に記載のタンパク質:
(i)配列番号1に示されるアミノ酸配列からなるタンパク質、又は
(ii)配列番号1に示されるアミノ酸配列と70%以上の同一性を有するアミノ酸配列からなり、且つアルケニル型リゾリン脂質に対してホスホリパーゼD活性を有するタンパク質である、請求項1~7のいずれかに記載の剤。

[請求項9]
ホスホリパーゼD及びその発現カセットからなる群より選択される少なくとも1種を含有する、表皮肥厚性疾患の予防又は治療剤。

[請求項10]
ホスホリパーゼD及びその発現カセットからなる群より選択される少なくとも1種を含有する、乾癬、接触性皮膚炎(かぶれ)、皮膚がん、アトピー性皮膚炎、疣贅、角化症、胼胝、鶏眼、及び水虫からなる群より選択される少なくとも1種の疾患の予防又は治療剤。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • TOKUSHIMA UNIVERSITY
  • TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
  • Inventor
  • YAMAMOTO Kei
  • MURAKAMI MAKOTO
  • SAKASEGAWA Shinichi
IPC(International Patent Classification)
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