WO2006051987A1 - Nouveau medicament servant a inhiber des maladies dependantes des oestrogenes, des maladies gynecologiques dependantes de la prostaglandine d (pgd), des maladies immunologiques, le cancer et l'angiogenese - Google Patents

Nouveau medicament servant a inhiber des maladies dependantes des oestrogenes, des maladies gynecologiques dependantes de la prostaglandine d (pgd), des maladies immunologiques, le cancer et l'angiogenese Download PDF

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Publication number
WO2006051987A1
WO2006051987A1 PCT/JP2005/020958 JP2005020958W WO2006051987A1 WO 2006051987 A1 WO2006051987 A1 WO 2006051987A1 JP 2005020958 W JP2005020958 W JP 2005020958W WO 2006051987 A1 WO2006051987 A1 WO 2006051987A1
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Prior art keywords
gene
diseases
dependent
hrf
disease
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PCT/JP2005/020958
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English (en)
Japanese (ja)
Inventor
Yoshinori Kosugi
Masahiko Kuroda
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Periodock, Co., Ltd.
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Publication date
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Priority to JP2006545068A priority Critical patent/JPWO2006051987A1/ja
Publication of WO2006051987A1 publication Critical patent/WO2006051987A1/fr

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    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/06—Antiabortive agents; Labour repressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30—Oestrogens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/32—Antioestrogens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the medicament of the present invention is a medicament for at least one selected from the group consisting of estrogen-dependent diseases, PGD-dependent gynecological diseases, immune diseases, cancer and angiogenesis inhibition.
  • HRF histamine-releasing factor
  • TCTP Translationally controlled tumor protein
  • the present invention includes food for specified health use, nutrient functional food or general food containing an HRF activity-suppressing ingredient as other embodiments.
  • the general food and the HRF activity-suppressing component are the same as those of the pharmaceutical product of the present invention.
  • transcript variant 2 mRNA.
  • TGF- ⁇ induced apotosis protein 2 (TAIP-2), mRNA.
  • N _005259 2.207261735 synonym: MSTN; myostatin; plasma glycoprotein: TGFjS receptor signaling
  • MAPK calcium-mediated signaling
  • regulation of RAS protein signal transduction regulation of cell growth
  • regulation of protein kinase activity regulation of smooth muscle contraction
  • RAB7 mRNA
  • NM_021970 199.9990508 synonym MEK partner 1; MEK binding partner 1; mitogen-activated protein
  • MAP2K1 IP1 kinase kinase 1 interacting protein 1
  • Fig. 2 is an LC-MS total ion chromatogram of the artemisinin preparation used in the examples of the present invention
  • Fig. 3 is an MS pattern of the relative retention time of the artemisinin preparation of 3.42 minutes. . From these results, the artemisinin preparation was composed of artemisinin and a small amount of dihydroartemisinin.
  • HRF producing cells that specifically react with HRF were established, and these producing cells were administered into the mouse abdominal cavity.
  • the obtained mouse ascites was purified with a protein G column to obtain a highly pure monoclonal IgG antibody.
  • This monoclonal antibody that specifically recognizes HRF was dissolved in sodium bicarbonate buffer (0.1 M, pH 9.5) at a concentration of 10 lZml in advance, and this was dissolved in a 96-well immunoplate for ELISA. 100 ⁇ L each was added and allowed to stand at 4 ° C. to allow the antibody to bind to the plate.
  • HRF standard antigen (baculovirus-derived recombinant antigen: 2000, 1000, 500, 250, 125, 63 , 32, 16, 8, 4, 2, 1, OngZmL) was added at 100 L per well, left at room temperature for 2 hours, and washed 3 times with PBS containing 0.05% Tween20 (trade name).
  • 100 ⁇ L per well of anti-rabbit HRF antibody polyclonal antibody obtained by immunizing subcutaneously with a synthetic peptide antigen (15 amino acid residues) having an HRF antigen active site
  • the mixture was allowed to stand at room temperature for 1 hour, and washed with PBS containing 0.05% Tween20 (trade name) three times.
  • Fig. 4 shows the calibration curve obtained.
  • the degree of dysmenorrhea was determined using the score table shown in Table 4 below based on subjective symptoms and use of analgesics.
  • This score table is a modified version of Andersch's method with reference to Bileroglu's method.
  • the score was used to assess the extent of patients with dysmenorrhea (including endometriosis). Based on the evaluation results, two patients who were considered to have severe symptoms were assigned to the administration group, and these artemisinin preparations were administered to these patients in an amount of lOOmg per day for 5 months. On the other hand, the symptoms were milder than those in the above-mentioned administration group, and 2 patients were assigned to the non-administration group. About the said patient, HRF activity was measured every month and the symptom was confirmed. The measurement result of HRF activity is shown in FIG. 5, and the change in score is shown in Table 5 below.
  • the measurement of the HRF activity was performed in the same manner as in the preparation of the calibration curve (1) except that serum or menstrual blood from the subject was used instead of the HRF standard antigen, and the calibration curve was used. The amount of HRF bound to the antibody was determined, and this was defined as HRF activity.
  • the pharmaceutical agent of the present invention is useful as a pharmaceutical agent for preventing, treating or ameliorating estrogen-dependent diseases, infertility and immune diseases, and a pharmaceutical agent for suppressing angiogenesis.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Obesity (AREA)
  • Pregnancy & Childbirth (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention a pour objet un médicament servant à inhiber des maladies dépendantes des oestrogènes, des maladies gynécologiques dépendantes de la prostaglandine D (PGD), des maladies immunologiques, le cancer et l'angiogenèse. A savoir que l'invention concerne un médicament visant à inhiber au moins un élément sélectionné dans le groupe constitué des maladies dépendantes des oestrogènes, des maladies gynécologiques dépendantes de la PGD, des maladies immunologiques, du cancer et de l'angiogenèse, caractérisé en ce qu'il contient un ingrédient inhibant l'activité d'un facteur libérant l'histamine (HRF). En inhibant l'activité d'un HRF, l'expression de gènes, par exemple du récepteur de l'IL-1ß, de la 17ß-hydroxystéroïde déshydrogénase (HSD), etc. est inhibée. Ainsi, l'activité des oestrogènes est inhibée et on peut prévenir, traiter ou améliorer de cette manière des maladies dépendantes des oestrogènes. On préfère utiliser l'artémisinine comme ingrédient inhibant l'activité d'un HRF décrit ci-dessus.
PCT/JP2005/020958 2004-11-15 2005-11-15 Nouveau medicament servant a inhiber des maladies dependantes des oestrogenes, des maladies gynecologiques dependantes de la prostaglandine d (pgd), des maladies immunologiques, le cancer et l'angiogenese WO2006051987A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2006545068A JPWO2006051987A1 (ja) 2004-11-15 2005-11-15 エストロゲン依存性疾患、プロスタグランジンｄ（ｐｇｄ）依存性婦人疾患、免疫疾患、癌及び血管新生抑制のための新規医薬品

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2004-331230 2004-11-15
JP2004331230 2004-11-15

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WO2006051987A1 true WO2006051987A1 (fr) 2006-05-18

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010110747A1 (fr) * 2009-03-24 2010-09-30 National University Of Singapore Utilisation de dérivés de l'artémisinine dans le traitement de l'asthme et de la broncho-pneumopathie obstructive chronique (bpco)
CN103230455A (zh) * 2013-04-12 2013-08-07 成都绿迪科技有限公司 一种治疗子宫内膜异位症的中药组合物
CN104127600A (zh) * 2014-08-19 2014-11-05 孟洁 一种用于小儿祛痰的药物组合物及其应用
CN115702893A (zh) * 2021-08-16 2023-02-17 复旦大学 青蒿素类似物在制备降低雄激素药物以及治疗与高雄激素水平有关的疾病的药物中的应用

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CN1241569A (zh) * 1999-04-30 2000-01-19 四川三奇制药有限责任公司 从青蒿素母液中提取青蒿油的方法
WO2000004026A1 (fr) * 1998-07-14 2000-01-27 The Hong Kong University Of Science & Technology Derives de trioxane
EP1167526A1 (fr) * 2000-06-01 2002-01-02 Kyunglim Lee Récepteur de facteur liberant l'histamine dependant de l'IgE, péptides se liant, acides nucleiques codant ces protéines, et leur utilisations
CN1392252A (zh) * 2001-06-15 2003-01-22 中国科学院化工冶金研究所 提高青蒿器官生物量和青蒿素含量的培养方法
WO2003097835A2 (fr) * 2002-05-16 2003-11-27 Molecular Engines Laboratories Compositions et procedes destines au traitement du cancer
WO2004041280A1 (fr) * 2002-11-02 2004-05-21 Kyung-Lim Lee Composition destinee a prevenir la secretion du facteur de liberation de l'histamine dependant de l'immunoglobuline e
WO2005005983A1 (fr) * 2003-07-14 2005-01-20 Japan Science And Technology Agency Procede pour diagnostiquer des maladies associees a une endometriose
WO2005005984A1 (fr) * 2003-07-14 2005-01-20 Periocock Co., Ltd. Procede pour diagnostiquer des maladies associees a une endometriose

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CN1241569A (zh) * 1999-04-30 2000-01-19 四川三奇制药有限责任公司 从青蒿素母液中提取青蒿油的方法
EP1167526A1 (fr) * 2000-06-01 2002-01-02 Kyunglim Lee Récepteur de facteur liberant l'histamine dependant de l'IgE, péptides se liant, acides nucleiques codant ces protéines, et leur utilisations
CN1392252A (zh) * 2001-06-15 2003-01-22 中国科学院化工冶金研究所 提高青蒿器官生物量和青蒿素含量的培养方法
WO2003097835A2 (fr) * 2002-05-16 2003-11-27 Molecular Engines Laboratories Compositions et procedes destines au traitement du cancer
WO2004041280A1 (fr) * 2002-11-02 2004-05-21 Kyung-Lim Lee Composition destinee a prevenir la secretion du facteur de liberation de l'histamine dependant de l'immunoglobuline e
WO2005005983A1 (fr) * 2003-07-14 2005-01-20 Japan Science And Technology Agency Procede pour diagnostiquer des maladies associees a une endometriose
WO2005005984A1 (fr) * 2003-07-14 2005-01-20 Periocock Co., Ltd. Procede pour diagnostiquer des maladies associees a une endometriose

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BHISUTTHIBHAN J. ET AL.: "The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin", J. BIOL. CHEM., vol. 273, no. 26, 1998, pages 16192 - 16198, XP002997564 *
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010110747A1 (fr) * 2009-03-24 2010-09-30 National University Of Singapore Utilisation de dérivés de l'artémisinine dans le traitement de l'asthme et de la broncho-pneumopathie obstructive chronique (bpco)
US8293783B2 (en) 2009-03-24 2012-10-23 National University Of Singapore Use of artemisinin derivatives for the treatment of asthma and chronic obstructive pulmonary disease (COPD)
CN103230455A (zh) * 2013-04-12 2013-08-07 成都绿迪科技有限公司 一种治疗子宫内膜异位症的中药组合物
CN104127600A (zh) * 2014-08-19 2014-11-05 孟洁 一种用于小儿祛痰的药物组合物及其应用
CN115702893A (zh) * 2021-08-16 2023-02-17 复旦大学 青蒿素类似物在制备降低雄激素药物以及治疗与高雄激素水平有关的疾病的药物中的应用

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