WO2004103406A1 - Composition therapeutique contre des maladies s'accompagnant d'une dimension ou d'une augmentation des plaquettes - Google Patents

Composition therapeutique contre des maladies s'accompagnant d'une dimension ou d'une augmentation des plaquettes Download PDF

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Publication number
WO2004103406A1
WO2004103406A1 PCT/JP2004/007566 JP2004007566W WO2004103406A1 WO 2004103406 A1 WO2004103406 A1 WO 2004103406A1 JP 2004007566 W JP2004007566 W JP 2004007566W WO 2004103406 A1 WO2004103406 A1 WO 2004103406A1
Authority
WO
WIPO (PCT)
Prior art keywords
platelets
megakaryocytes
substance
active ingredient
increase
Prior art date
Application number
PCT/JP2004/007566
Other languages
English (en)
Japanese (ja)
Inventor
Yuka Nagata
Kazuo Todokoro
Original Assignee
Japan Science And Technology Agency
The Institute Of Physical And Chemical Research (Riken)
Mochida Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Japan Science And Technology Agency, The Institute Of Physical And Chemical Research (Riken), Mochida Pharmaceutical Co., Ltd. filed Critical Japan Science And Technology Agency
Publication of WO2004103406A1 publication Critical patent/WO2004103406A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/02—Halogenated hydrocarbons
    • A61K31/025—Halogenated hydrocarbons carbocyclic
    • A61K31/03—Halogenated hydrocarbons carbocyclic aromatic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
    • C12Q1/32—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving dehydrogenase
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

Definitions

  • the present invention relates to a novel megakaryocyte-containing platelet production containing a substance having an activity of activating or inhibiting 3] 3-hydroxydehydrogenase (hereinafter sometimes abbreviated as “3j3 HSD”). Of the regulator.
  • Factors that enhance production by NF-E2 include ⁇ 1-tupurin (Lecine, P.), Blood, (USA), 2000, 96, p. 1366-1373) and thrompoxane synthase (Deveaux, S.), et al., EMBO Journal, (UK), 1999, Volume 16, p. 56 54- 5661), but none of them can restore PNF and platelet production from NF-E2_z-mouse ES cells.
  • a modulator comprising a substance having an action of activating 3-hydroxydehydrogenase and having an action of increasing platelet production from megakaryocytes.
  • a method for increasing megakaryocyte platelet production by bringing an estrogen receptor agonist into contact with a megakaryocyte in vitro is provided.
  • FIG. 3 is a graph showing the measurement results of PPF in Example 2, in which the PPF of the control is shown as 100%.
  • the substances exemplified as the substances contained in the modulators of the first and second embodiments have a 3/3 HSD activating or inhibiting action.
  • the above-mentioned liothyronine (InM) or trilostane (100 ⁇ ⁇ ) promotes or suppresses progesterone secretion by bush luteal cells (Gregoraschuk, ii. Elire. (Grego raszczuk, EL), etc.)
  • End Klein Regulations End dcrine Re gu lation s), 1999, Vol. 33, p.
  • Medroxyprogesterone is marketed in Japan in the form of acetate, such as Hythron TM (Kyowa Hakko Kogyo Co., Ltd.), a therapeutic agent for amenorrhea. All of the above drugs are highly safe drugs and are available.
  • the modulators of the first and second embodiments are useful as experimental modulators for studying the mechanism of platelet production from megakaryocytes. Therefore, the present invention provides, as a third aspect, a method for regulating the production of platelets from megakaryocytes using the modulator of the first aspect or the second aspect.
  • combination refers to a compound that is an active ingredient of a composition for treating a disease associated with a decrease or increase in platelets of the present invention and a substance that promotes differentiation and maturation of megakaryocytes, or a myelosuppressant and / or an antiplatelet And two or more drugs, each of which is separately contained, and these drugs can be administered simultaneously or sequentially, or a mixture of these In the form of co-administration.
  • the modulator of the sixth aspect or the seventh aspect when added, Can increase platelet production by increasing PPF from megakaryocytes.
  • the regulator of the seventh embodiment when the regulator of the seventh embodiment is added, PPF from megakaryocytes after culture can be reduced, and platelet production can be reduced.
  • test substance was added to the cultured megakaryocytes, and the results obtained by measuring the PPF were evaluated.
  • the test substance contains a substance having a 3j8 HSD activating or inhibitory action of the present invention as an active ingredient, thereby providing a composition for treating a disease associated with a decrease or increase in platelets. Screening for what can be done can be done.
  • Example 6 the composition for treating a disease associated with decrease or increase of platelets, which comprises a substance having an activity of activating or inhibiting 3 iS HSD of the present invention as an active ingredient.
  • the production example which produced the pharmaceutical preparation is shown.
  • Example 6 Riothyronine sustained release tablet
  • tablets of a composition for treating a disease associated with an increase in platelets comprising medroxyprogesterone acetate as a substance having a 3j3HSD inhibitory action, were produced.
  • medroxyprogesterone acetate as a substance having a 3j3HSD inhibitory action
  • the method for screening a composition for treating a disease associated with a decrease or increase in platelets which comprises a substance having a 3 jS HSD activating or inhibiting action according to the present invention as an active ingredient, comprises: It is useful as a method for efficiently identifying therapeutic agents for various diseases and substances for use in treatment and research for diseases associated with thrombocytopenia or increase.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Oncology (AREA)
  • Diabetes (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne une composition thérapeutique contre des maladies s'accompagnant d'une diminution ou d'une augmentation des plaquettes, laquelle est capable d'augmenter ou de diminuer sélectivement les plaquettes, présentant moins d'effet sur d'autres constituants hématocytes et n'impliquant aucune circulation extracorporelle, transfusion de sang total et transfusion de constituants sanguins, assurant moins d'effets secondaires. L'invention concerne notamment une composition thérapeutique contre des maladies accompagnées d'une réduction des plaquettes ou de maladies accompagnées d'une augmentation de plaquettes, comprenant une substance présentant une activité activant ou une activité inhibant la 3β-hydroxydéshydrogénase.
PCT/JP2004/007566 2003-05-26 2004-05-26 Composition therapeutique contre des maladies s'accompagnant d'une dimension ou d'une augmentation des plaquettes WO2004103406A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2003147820 2003-05-26
JP2003-147820 2003-05-26
JP2003-398876 2003-11-28
JP2003398876 2003-11-28

Publications (1)

Publication Number Publication Date
WO2004103406A1 true WO2004103406A1 (fr) 2004-12-02

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2004/007566 WO2004103406A1 (fr) 2003-05-26 2004-05-26 Composition therapeutique contre des maladies s'accompagnant d'une dimension ou d'une augmentation des plaquettes

Country Status (1)

Country Link
WO (1) WO2004103406A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8227457B2 (en) 2009-06-22 2012-07-24 Dmi Acquisition Corp. Method for treatment of diseases
EP2468282A3 (fr) * 2005-07-12 2012-09-12 DMI Biosciences, Inc. Procédés et produits de traitement des maladies
US8376729B2 (en) 2010-02-01 2013-02-19 Mecpart S.P.A. Roller compactor integrated to a wheel track machine for laboratory tests on bituminous mixes
US9351979B2 (en) 2012-12-19 2016-05-31 Ampio Pharmaceuticals, Inc. Methods of treatment of diseases

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
KHETAWAT G. ET AL: "Human megakaryocytes and platelets contain the estrogen receptor beta and androgen receptor (AR): testosterone regulates AR expression", BLOOD, vol. 95, no. 7, 1 April 2000 (2000-04-01), pages 2289 - 2296, XP002980863 *
MATSUMURA I. ET AL: "Molecular Control of Megakaryopoiesis and Thrombopoiesis", INT. J. HEMATOL., vol. 75, no. 5, June 2002 (2002-06-01), pages 473 - 483, XP002980862 *
TARANTINO M.D. ET AL: "The Estrogen Receptor is Present in Human Megakaryocytes", ANNALS NY ACAD. SCI., vol. 714, 18 April 1994 (1994-04-18), pages 293 - 296, XP002980864 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2468282A3 (fr) * 2005-07-12 2012-09-12 DMI Biosciences, Inc. Procédés et produits de traitement des maladies
US8586568B2 (en) 2005-07-12 2013-11-19 Ampio Pharmaceuticals, Inc. Methods and products for treatment of diseases
US8722651B2 (en) 2005-07-12 2014-05-13 Ampio Pharmaceuticals, Inc. Methods and products for treatment of diseases
US8227457B2 (en) 2009-06-22 2012-07-24 Dmi Acquisition Corp. Method for treatment of diseases
US9233113B2 (en) 2009-06-22 2016-01-12 Ampio Pharmaceuticals, Inc. Method for treatment of diseases
US9987292B2 (en) 2009-06-22 2018-06-05 Ampio Pharmaceuticals, Inc. Method for treatment of diseases
US8376729B2 (en) 2010-02-01 2013-02-19 Mecpart S.P.A. Roller compactor integrated to a wheel track machine for laboratory tests on bituminous mixes
US9351979B2 (en) 2012-12-19 2016-05-31 Ampio Pharmaceuticals, Inc. Methods of treatment of diseases
US10058562B2 (en) 2012-12-19 2018-08-28 Ampio Pharmaceuticals, Inc. Methods of treatment of diseases

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