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NOVEL K95-5901-1 SUBSTANCE AND METHOD FOR PRODUCING SAME NEW_EN

Foreign code F190009998
File No. (S2018-0527-N0)
Posted date Oct 30, 2019
Country WIPO
International application number 2019JP013132
International publication number WO 2019189331
Date of international filing Mar 27, 2019
Date of international publication Oct 3, 2019
Priority data
  • P2018-061397 (Mar 28, 2018) JP
Title NOVEL K95-5901-1 SUBSTANCE AND METHOD FOR PRODUCING SAME NEW_EN
Abstract As a result of searching for an antibiotic substance effective for multidrug-resistant Mycobacterium tuberculosis in a microorganism culture solution, the present inventors discovered a novel substance K95-5901-1 having the following structure, within products of an actinobacterium, Actinoplanes sp. K95-5901. This substance expresses a proliferation-inhibiting activity to multidrug-resistant Mycobacterium tuberculosis at a concentration lower than micromole level, and has a very weak cytotoxicity. Consequently, based on this discovery, the present invention provides a novel substance having a proliferation-inhibition activity on Mycobacterium tuberculosis.
Outline of related art and contending technology BACKGROUND ART
2 Tuberculosis infection is specified to include 3 and 1 is one large infection, HIV/AIDS infections include the following single 2 a large number of deaths in the world the second disease. 1,040 Tuberculosis million patient reported that, by year 170 million people died tuberculosis (2016 years, WHO). HIV infection in the user, the tuberculosis 1 5 occupy the third leading cause of death. With respect to the treatment of tuberculosis, as first, rifampicin, isoniazid, ethambutol, streptomycin, ethambutol is, as the second choice, levofloxacin, kanamycin, antileprosy, , para-aminosalicylic acid, cycloserine been used, used in combination of two or more agents 3.
In recent years, a multi-drug resistance resistant to a therapeutic agent of tuberculosis is, the trend for the spread. Rifampicin resistant to the drug of choice for 60 years may be applied to a case of the upstream one million, 49 million of them are multi-drug resistance is considered. Multidrug resistant tuberculosis further and the existing anti-tuberculosis drug resistant tuberculosis shown no effect on the appearance of an ultra-multi-more than half of the world seen in the countries, these measures are in the urgent international society has been a problem.
However, these therapeutic agents by reducing the number of patients newly industrialized countries in association with, the development of new anti-tuberculosis drugs is reduced, the new anti-tuberculosis agent is 40 years on the market and also not 1. Multidrug-resistant tuberculosis and as one of measures against tuberculosis of the ultra-multi, effective against these, in the conventional structure and mechanism of action of therapeutic agents of the different is demanded the development of new therapeutic agents.
Such as an anti-tuberculosis drug, nitroimidazole-based compound, such as CPZEN-45/caprazamycin, Clp protease and the disturbance material has been studied (Non-Patent Document 1). Clp protease disturbance material which is one type of marine is cyclo marin (cyclomarin) from Streptomyces sp. obtained from actinomycetes in heptapeptides. Is cyclo marin, tuberculosis ClpC1 Clp of the action of the sub-units, and run the function to induce cell death. Streptomyces atratusSCSIO ZH16 iramaishin from deep water is isolated from the cyclo marin and analogous compounds, Clp protease disturbance material in the same manner as thought. C of a plurality of homologs iramaishin iramaishin represented by the following structure is a compound, the compound activity against drug resistant tuberculosis (Mycobacteria tuberculosis H37Rv) have been reported to be as low as 9.6μm (Non-Patent Document 2).
Scope of claims (In Japanese)[請求項1]
 下記式(I)で表される化合物若しくはその塩、又はそれらの水和物若しくは溶媒和物。
[化1]
(省略)
[請求項2]
 放線菌に属する上記式(I)で表される化合物を生産する能力を有する微生物を培地で培養し、培養物中に前記化合物を蓄積せしめ、該培養物から前記化合物を採取することを含む、請求項1に記載の化合物の製造方法。

[請求項3]
 放線菌に属する上記式(I)で表される化合物を生産する能力を有する微生物が、アクチノプラネス属に属する微生物である、請求項2に記載の製造法。

[請求項4]
 放線菌に属する上記式(I)で表される化合物を生産する能力を有する微生物が、アクチノプラネス・エスピー(Actinoplanes sp.)K95-5901(受託番号NITE BP-02658)である請求項3に記載の製造法。

[請求項5]
 放線菌に属し、K95-5901-1物質を生産する能力を有する微生物。

[請求項6]
 アクチノプラネス・エスピー(Actinoplanes sp.)K95-5901(受託番号NITE BP-02658)株。

[請求項7]
 請求項1に記載の化合物若しくはその塩、又はそれらの水和物若しくは溶媒和物を有効成分として含有する、医薬組成物。

[請求項8]
 抗結核薬である、請求項7に記載の医薬組成物。

[請求項9]
 結核菌増殖阻害剤である、請求項8に記載の医薬組成物。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • THE KITASATO INSTITUTE
  • HOKKAIDO UNIVERSITY
  • Inventor
  • OMURA Satoshi
  • SHIOMI Kazuro
  • MORI Mihoko
  • MATSUMOTO, Atsuko
  • SUZUKI, Yasuhiko
  • NAKAJIMA, Chie
  • YAMAGUCHI Tomoyuki
IPC(International Patent Classification)
Specified countries 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 DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW 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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