WO2011036879A1 - Préparation de liposome de transferrine - Google Patents

Préparation de liposome de transferrine Download PDF

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Publication number
WO2011036879A1
WO2011036879A1 PCT/JP2010/005752 JP2010005752W WO2011036879A1 WO 2011036879 A1 WO2011036879 A1 WO 2011036879A1 JP 2010005752 W JP2010005752 W JP 2010005752W WO 2011036879 A1 WO2011036879 A1 WO 2011036879A1
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WO
WIPO (PCT)
Prior art keywords
tfr1
cells
expression
transferrin
myc
Prior art date
Application number
PCT/JP2010/005752
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English (en)
Japanese (ja)
Inventor
茂弘 大戸
直哉 松永
悟 小柳
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国立大学法人九州大学
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Filing date
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Application filed by 国立大学法人九州大学 filed Critical 国立大学法人九州大学
Publication of WO2011036879A1 publication Critical patent/WO2011036879A1/fr

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    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6905—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
    • A61K47/6911—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • FIG. 1A is a photograph which shows 24 hour fluctuation
  • FIG. 1B is a graph showing a temporal expression profile of TfR1 mRNA in a tumor.
  • FIG. 2A is a schematic diagram of the mouse TfR1 promoter, and FIG. 2B is a graph showing the effects of CLOCK / BMAL1 and c-MYC on mouse TfR1 gene transcription.
  • FIG. 1A is a photograph which shows 24 hour fluctuation
  • FIG. 1B is a graph showing a temporal expression profile of TfR1 mRNA in a tumor.
  • FIG. 2A is a schematic diagram of the mouse TfR1 promoter, and FIG. 2B is a graph showing the effects of CLOCK
  • TfR1 protein and mRNA levels were measured by Western blotting analysis and quantitative reverse transcription PCR (RT-PCR), respectively.
  • RT-PCR quantitative reverse transcription PCR
  • Tf-NGPE L-OHP oxaliplatin-encapsulated Tf-bound liposomes
  • c-MYC is a strong activator of TfR1 gene transcription in mice and humans, and the transactivation effect is induced by binding to the CACGTG E-box located in the first intron region, and further, CLOCK / BMAL1 heterozygous Dimers also bind cooperatively with CACGTG E-box sequences and control the cyclic expression of their target genes. Therefore, CLOCK ⁇ 19 (a transcriptional activity-deficient CLOCK protein) was overexpressed in Colon26 cells to establish that the biological clock system is related to TfR1 expression.
  • FIG. 6 shows the effect of administration time on Tf-PEG L-OHP ability to inhibit tumor growth in mice.
  • a single dose of Tf-NGPE L-OHP (L-OHP: 7.5 mg / kg) or vehicle (9% sucrose) was intravenously injected at 9 am or 9 pm into Colon26 cell transplanted mice.
  • FIG. 6A shows the difference in the administration time dependency of L-OHP in the tumor delivered by Tf-NGPE liposome.
  • FIG. 6A shows the plasma Pt concentration on the left and FIG. 6A shows the Pt to the tumor DNA. It indicates uptake and was measured at the indicated time after Tf-NGPE L-OHP injection.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une préparation de liposome de transferrine dans laquelle un agent anticancéreux est encapsulé et dont la temporisation d'administration est optimisée. La présente invention concerne spécifiquement une préparation de liposome de transferrine comprenant un liposome dans lequel de la transferrine est liée à celui-ci par l'intermédiaire de NGPE et un agent anticancéreux tel que L-OHP encapsulé dans le liposome. La préparation de liposome de transferrine est caractérisée en ce qu'elle est utilisée de sorte que la préparation soit administrée à un temps auquel l'expression de TfR1 est augmentée ou administrée de manière à coïncider avec l'expression circadienne de C-Myc.
PCT/JP2010/005752 2009-09-22 2010-09-22 Préparation de liposome de transferrine WO2011036879A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US24455309P 2009-09-22 2009-09-22
US61/244,553 2009-09-22

Publications (1)

Publication Number Publication Date
WO2011036879A1 true WO2011036879A1 (fr) 2011-03-31

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Family Applications (1)

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PCT/JP2010/005752 WO2011036879A1 (fr) 2009-09-22 2010-09-22 Préparation de liposome de transferrine

Country Status (1)

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WO (1) WO2011036879A1 (fr)

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ISHIDA, O. ET AL.: "Liposomes bearing polyethyleneglycol-coupled transferrin with intracellulartargeting property to the solid tumors in vivo.", PHARM RES., vol. 18, no. 7, 2001, pages 1042 - 8, XP008013367, DOI: doi:10.1023/A:1010960900254 *
OKAZAKI, F. ET AL.: "Circadian Rhythm of Transferrin Receptor 1 Gene Expression Controlled by c-Myc in Colon Cancer-Bearing Mice", CANCER RESEARCH, vol. 70, no. 15, 2010, pages 6238 - 6246 *
ROEHRS, S. ET AL.: "Chronological expression of Wnt target genes Ccndl, Myc, Cdknla, Tfrc, Plf1 and Ramp3", CELL BIOLOGY INTERNATIONAL, vol. 33, no. 4, April 2009 (2009-04-01), pages 501 - 508 *
SUZUKI, R. ET AL.: "Effective anti-tumor activity of oxaliplatin encapsulated in transferrin-PEG-liposome.", INT J PHARM., vol. 346, no. 1-2, 2007, pages 143 - 50, XP022348373, DOI: doi:10.1016/j.ijpharm.2007.06.010 *

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