WO2017014312A1 - Agent pour le traitement / l'amélioration de maladies de prolifération dépendantes des hormones féminines - Google Patents

Agent pour le traitement / l'amélioration de maladies de prolifération dépendantes des hormones féminines Download PDF

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Publication number
WO2017014312A1
WO2017014312A1 PCT/JP2016/071604 JP2016071604W WO2017014312A1 WO 2017014312 A1 WO2017014312 A1 WO 2017014312A1 JP 2016071604 W JP2016071604 W JP 2016071604W WO 2017014312 A1 WO2017014312 A1 WO 2017014312A1
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WIPO (PCT)
Prior art keywords
emp9
treatment
tissue
cells
glandular
Prior art date
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Ceased
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PCT/JP2016/071604
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English (en)
Japanese (ja)
Inventor
佳子 安田
昊 星合
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cellpep Co Ltd
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Cellpep Co Ltd
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Filing date
Publication date
Application filed by Cellpep Co Ltd filed Critical Cellpep Co Ltd
Publication of WO2017014312A1 publication Critical patent/WO2017014312A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to a therapeutic / ameliorating agent for female hormone-dependent proliferative diseases.
  • Non-Patent Document 5 Yasuda et al., Develop. Growth Differ., Vol. 35, pp 711-722 (1993)
  • human, monkey and mouse brains Non-patent document 6: Marti H. H. et al., Eur. J. Neu. Sci., Vol. 8, pp 666-676 (1996)
  • Human placenta Non-Patent Document 7: Conrad et al., BFASEB. J., Vol. 10, pp 760-768 (1996)
  • the human or mammalian tissue or cell is homogenized and then extracted with an acid or the like.
  • chromatography such as reverse phase chromatography and ion exchange chromatography.
  • Examples of the protecting group for the amino group of the raw material include Z, Boc, tert-pentyloxycarbonyl, isobornyloxycarbonyl, 4-methoxybenzyloxycarbonyl, C1-Z, Br-Z, adamantyloxycarbonyl, and trifluoroacetyl. Phthaloyl, formyl, 2-nitrophenylsulfenyl, diphenylphosphinothioyl, Fmoc, and the like.
  • groups suitable for esterification include groups derived from carbonic acid such as lower alkanoyl groups such as acetyl groups, aroyl groups such as benzoyl groups, benzyloxycarbonyl groups, and ethoxycarbonyl groups.
  • groups suitable for etherification include a benzyl group, a tetrahydropyranyl group, and a tert-butyl group.
  • Examples of the protecting group for the phenolic hydroxyl group of tyrosine include Bzl, Cl 2 -Bzl, 2-nitrobenzyl, Br-Z, tert-butyl and the like.
  • the ⁇ -carboxyl group of the carboxyl terminal amino acid is amidated and protected, and then the peptide chain is extended to the desired chain length on the amino group side. Thereafter, a partial peptide from which only the protecting group for the ⁇ -amino group at the N-terminal of the peptide chain was removed and a partial peptide from which only the protecting group for the carboxyl group at the C-terminal was removed were prepared.
  • the condensation is performed in such a mixed solvent. The details of the condensation reaction are the same as described above.
  • the agent of the present invention can be used in combination with an appropriate amount of another drug or in combination with an appropriate amount.
  • concomitant drugs include various hormone preparations that can be used for treatment of female hormone-dependent growth. Specific examples include drugs with low immunosuppressive action, such as GnRH agonists, anti-estrogen preparations and aromatase inhibitors, secretory therapeutic agents (LH-RH agonists and antagonists, sex hormone antagonists, sex hormone synthesis inhibitors, etc.) and the like. It is done.
  • an autonomic nerve blocker such as phentolamine which is an ⁇ 1 -blocker or an atropine preparation can be used in combination with the agent of the present invention.
  • the administration timing of the agent of the present invention and the concomitant drug is not limited, and the agent of the present invention and the concomitant drug may be administered simultaneously to the administration subject. Alternatively, administration may be performed with a time difference.
  • the dose of the concomitant drug may be determined according to the dose used clinically, and can be appropriately selected depending on the administration subject, administration route, disease, combination and the like.
  • the administration mode of the agent of the present invention and the concomitant drug is not particularly limited as long as the agent of the present invention and the concomitant drug are combined at the time of administration.
  • the same content may be used when the erythropoietin receptor antagonist and the concomitant drug contained in the agent of the present invention are formulated separately.
  • the agent of the present invention and the pharmaceutical composition containing the concomitant drug are administered at the same time.
  • the agent of the present invention may be administered, or the pharmaceutical agent of the present invention is administered first, and then the concomitant drug is contained.
  • the product may be administered.
  • the time difference varies depending on the active ingredient, dosage form, and administration method to be administered.
  • bases and amino acids are represented by abbreviations, they are based on abbreviations by IUPAC-IUB Commission on Biochemical Nomenclature or conventional abbreviations in the field, and examples thereof are described below.
  • optical isomer with respect to an amino acid the L form is shown unless otherwise specified.
  • FIG. 14 is an H ⁇ E-stained image of the Hr (EMP9 15.0) specimen tissue showing the destruction of the glandular structure. Glandular destruction (large arrows, degree of destruction +3), matrix cell necrosis (small arrows), matrix cell thawing (marked *) and smooth muscle cell tissue defect (nucleusless / death **) .
  • the scale bar indicates 50 ⁇ m.
  • FIGS. 23 to 26 show specimens of glandular muscle species of nude mice.
  • FIG. 23 is a Mr 4.0 treated adenomyoma, where the arrow is the branch tumor feeding artery from the axillary artery.
  • FIG. 24 shows the cross section of the tumor of FIG. 23 after formazan reaction, and the red part is positive and indicates survival.
  • FIG. 25 shows a cross section of an adenomyomatous treated with a Mr. saline solution after formazan reaction.
  • FIG. 26 shows an untreated adenomyoma after Mr transplantation. 15 days after the transplantation.
  • FIG. 31 is a histological image showing adenomyomas (Mr) in a saline treatment with aromatase staining.
  • a is an image showing glandular cyst formation (arrow)
  • b is a strongly magnified image of a, and shows aromatase localization (small arrow).
  • the scale bar indicates 20 ⁇ m.
  • FIG. 39 is a histological image showing the localization of EpoR and EstR ⁇ expressed in BPH tissue.
  • a is an image obtained by staining a gland and smooth muscle with an anti-EpoR antibody
  • an arrow indicates a glandular epithelial cell
  • an asterisk indicates a smooth muscle cell.
  • b is an image of a smooth muscle cell group (arrow) expressing EpoR
  • c is an image of Sm-myosin of a smooth muscle cell (the staining is shaded, arrow)
  • d is an EstR ⁇ in a smooth muscle cell. It is an image which shows (arrow).
  • a scale bar shows 20 micrometers.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne un agent pour le traitement / l'amélioration de maladies de prolifération dépendantes des hormones féminines contenant un peptide de faible poids moléculaire, en particulier un peptide mimétique de l'érythropoïétine (EMP), en particulier l'EMP9, possédant une activité d'antagoniste du récepteur de l'érythropoïétine. L'EMP9 est administré par voie intraveineuse ou directement au niveau du foyer de l'adénomyose, de l'endométriose, des fibroïdes utérins ou de la maladie de prolifération de l'organe de type hypertrophie bénigne de la prostate, celles-ci étant des maladies dépendantes des hormones féminines, et ces maladies peuvent être améliorées ou traitées.
PCT/JP2016/071604 2015-07-22 2016-07-22 Agent pour le traitement / l'amélioration de maladies de prolifération dépendantes des hormones féminines Ceased WO2017014312A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015-145108 2015-07-22
JP2015145108A JP5867949B1 (ja) 2015-07-22 2015-07-22 女性ホルモン依存性増殖性疾患治療・改善剤

Publications (1)

Publication Number Publication Date
WO2017014312A1 true WO2017014312A1 (fr) 2017-01-26

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PCT/JP2016/071604 Ceased WO2017014312A1 (fr) 2015-07-22 2016-07-22 Agent pour le traitement / l'amélioration de maladies de prolifération dépendantes des hormones féminines

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JP (1) JP5867949B1 (fr)
WO (1) WO2017014312A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020054813A1 (fr) * 2018-09-14 2020-03-19 エポメッド株式会社 Peptide récepteur anti-érythropoïétine

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10101574A (ja) * 1996-08-06 1998-04-21 Snow Brand Milk Prod Co Ltd 増殖性臓器疾患治療・改善剤
JP2003201252A (ja) * 2001-11-02 2003-07-18 Takeda Chem Ind Ltd 増殖性臓器疾患、慢性関節炎症性疾患、肥厚性瘢痕またはケロイド予防・治療剤

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003037377A1 (fr) * 2001-11-02 2003-05-08 Takeda Chemical Industries Ltd Agents prophylactiques/therapeutiques destines aux maladies des organes a evolution chronique, aux maladies arthritiques chroniques, aux cicatrices hypertrophiques ou cheloides

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10101574A (ja) * 1996-08-06 1998-04-21 Snow Brand Milk Prod Co Ltd 増殖性臓器疾患治療・改善剤
JP2003201252A (ja) * 2001-11-02 2003-07-18 Takeda Chem Ind Ltd 増殖性臓器疾患、慢性関節炎症性疾患、肥厚性瘢痕またはケロイド予防・治療剤

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YASUDA Y. ET AL.: "Erythropoietin Receptor Antagonist Suppressed Ectopic Hemoglobin Synthesis in Xenografts of HeLa Cells to Promote Their Destruction", PLOS ONE, vol. 10, no. 4, 15 April 2015 (2015-04-15), pages e 0122458, XP055348498 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020054813A1 (fr) * 2018-09-14 2020-03-19 エポメッド株式会社 Peptide récepteur anti-érythropoïétine
JPWO2020054813A1 (ja) * 2018-09-14 2021-08-30 エポメッド株式会社 抗エリスロポエチン受容体ペプチド
JP7445978B2 (ja) 2018-09-14 2024-03-08 エポメッド株式会社 抗エリスロポエチン受容体ペプチド
US12024571B2 (en) 2018-09-14 2024-07-02 Epo-Med Inc. Anti-erythropoietin receptor peptide

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JP5867949B1 (ja) 2016-02-24
JP2017025022A (ja) 2017-02-02

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