WO2020184128A1 - Préparation externe pour application locale contenant du sirolimus ou un dérivé de ce dernier - Google Patents

Préparation externe pour application locale contenant du sirolimus ou un dérivé de ce dernier Download PDF

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Publication number
WO2020184128A1
WO2020184128A1 PCT/JP2020/006717 JP2020006717W WO2020184128A1 WO 2020184128 A1 WO2020184128 A1 WO 2020184128A1 JP 2020006717 W JP2020006717 W JP 2020006717W WO 2020184128 A1 WO2020184128 A1 WO 2020184128A1
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WO
WIPO (PCT)
Prior art keywords
sirolimus
external preparation
weight
present
diethylene glycol
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2020/006717
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English (en)
Japanese (ja)
Inventor
眞理 金田
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.)
University of Osaka NUC
Original Assignee
Osaka University NUC
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 Osaka University NUC filed Critical Osaka University NUC
Publication of WO2020184128A1 publication Critical patent/WO2020184128A1/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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological 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
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Definitions

  • FIG. 1 is a graph showing the sirolimus concentration in the dermis and blood at each time after a single transdermal administration of 0.4% sirolimus-containing cream (SC), which is an embodiment of the external preparation of the present invention. is there.
  • (A) indicates the concentration in the dermis (ng / mg) and
  • (b) indicates the concentration in the blood (ng / ml).
  • the insertion graph of (b) is a graph in which the y-axis is enlarged.
  • N 6, ** P ⁇ 0.01)
  • FIG. 2 is a graph showing the sirolimus concentration in the dermis and blood at each time after a single transdermal administration of 0.8% sirolimus-containing gel (SG), which is a comparative preparation containing no diethylene glycol ether.
  • the upper limit of the dose is 2 mg / cm 2 or less, 1 mg / cm 2 or less, 0.5 mg / cm 2 or less, 0.1 mg / cm 2 or less, 0.05 mg / cm 2 or less, 0. 04mg / cm 2 or less, it may be 0.03 mg / cm 2 or less.
  • Examples of the higher alcohol which is an oily component contained in the external preparation of the present invention include stearyl alcohol, cetanol, myristyl alcohol, lauryl alcohol and oleyl alcohol.
  • the external preparation of the present invention preferably contains stearyl alcohol.
  • Oral preparation containing sirolimus A 1.25% sirolimus solution obtained by adding sirolimus to ethanol and dissolving it is mixed with a 9-fold amount of a physiological saline solution containing 0.1% Tween 20, and 1.25 mg of sirolimus in 1 ml. An oral preparation containing the above was obtained.
  • mice were injected intraperitoneally with an anesthetic (a combination of medetomidine 0.3 mg / kg, midazolam 4.0 mg / kg and butorphanol 5.0 mg / kg).
  • an E color (Natsume Seisakusho) was attached to the mouse to prevent grooming. The E-color was worn for up to 24 hours after administration of sirolimus.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Transplantation (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Le problème que cherche à résoudre la présente invention est de fournir une préparation externe contenant du sirolimus ou un dérivé de sirolimus, qui soit hautement efficace et très sûre. La solution apportée par l'invention concerne une préparation externe pour application locale contenant au moins un élément sélectionné dans le groupe constitué par le sirolimus et les dérivés du sirolimus, et l'éther de diéthylène glycol. Cette préparation externe est une formulation qui permet une pénétration efficace du sirolimus ou du dérivé du sirolimus dans l'épiderme, ainsi qu'une accumulation efficace dans le derme, avec une rétention dans le derme d'une forte concentration sur le long terme et quasiment aucun passage dans le sang. En conséquence, la formulation présente une efficacité élevée et une excellente sécurité d'emploi pour le traitement de lésions cutanées.
PCT/JP2020/006717 2019-03-08 2020-02-20 Préparation externe pour application locale contenant du sirolimus ou un dérivé de ce dernier Ceased WO2020184128A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2019042980A JP2022065223A (ja) 2019-03-08 2019-03-08 局所適用外用剤
JP2019-042980 2019-03-08

Publications (1)

Publication Number Publication Date
WO2020184128A1 true WO2020184128A1 (fr) 2020-09-17

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ID=72427340

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2020/006717 Ceased WO2020184128A1 (fr) 2019-03-08 2020-02-20 Préparation externe pour application locale contenant du sirolimus ou un dérivé de ce dernier

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Country Link
JP (1) JP2022065223A (fr)
WO (1) WO2020184128A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4085898A1 (fr) * 2021-05-05 2022-11-09 Sodha Pharma Consulting GmbH Formulation topique comprenant du sirolimus

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101366715A (zh) * 2007-08-15 2009-02-18 上海医药工业研究院 一种雷帕霉素组合物及其制备方法
CN105640886A (zh) * 2016-03-17 2016-06-08 中国人民解放军南京军区福州总医院 一种西罗莫司自微乳制剂及其制备方法
CN105663027A (zh) * 2016-04-01 2016-06-15 中国人民解放军广州军区武汉总医院 西罗莫司外用制剂、其制备方法及用途
WO2016114216A1 (fr) * 2015-01-13 2016-07-21 テルモ株式会社 Stent biodégradable

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101366715A (zh) * 2007-08-15 2009-02-18 上海医药工业研究院 一种雷帕霉素组合物及其制备方法
WO2016114216A1 (fr) * 2015-01-13 2016-07-21 テルモ株式会社 Stent biodégradable
CN105640886A (zh) * 2016-03-17 2016-06-08 中国人民解放军南京军区福州总医院 一种西罗莫司自微乳制剂及其制备方法
CN105663027A (zh) * 2016-04-01 2016-06-15 中国人民解放军广州军区武汉总医院 西罗莫司外用制剂、其制备方法及用途

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4085898A1 (fr) * 2021-05-05 2022-11-09 Sodha Pharma Consulting GmbH Formulation topique comprenant du sirolimus
WO2022233468A1 (fr) 2021-05-05 2022-11-10 Sodha Pharma Consulting Gmbh Formulation topique comprenant du sirolimus

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