WO2002083166A1 - Complexes de polymeres d'interferons et leur utilisation medicinale - Google Patents

Complexes de polymeres d'interferons et leur utilisation medicinale

Info

Publication number
WO2002083166A1
WO2002083166A1 PCT/JP2002/003563 JP0203563W WO02083166A1 WO 2002083166 A1 WO2002083166 A1 WO 2002083166A1 JP 0203563 W JP0203563 W JP 0203563W WO 02083166 A1 WO02083166 A1 WO 02083166A1
Authority
WO
WIPO (PCT)
Prior art keywords
polymer
interferon
disease
ifn
complex
Prior art date
Application number
PCT/JP2002/003563
Other languages
English (en)
Japanese (ja)
Inventor
Yasuhiko Tabata
Hidehito Matsuoka
Tatsuji Kurose
Kenji Murai
Original Assignee
Santen 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 Santen Pharmaceutical Co., Ltd. filed Critical Santen Pharmaceutical Co., Ltd.
Publication of WO2002083166A1 publication Critical patent/WO2002083166A1/fr

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Classifications

    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K47/51—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 non-active ingredient being a modifying agent
    • A61K47/56—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 non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A61K47/51—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 non-active ingredient being a modifying agent
    • A61K47/56—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 non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—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 non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a novel interferon-polymer complex, a method for producing the same, a medicinal use thereof, and a method for extending the duration of the drug effect of insulin.
  • IFN Infineon ferron
  • PEG polyethylene glycol
  • the present invention provides a medicine containing the IFN-polymer complex as an active ingredient, for example, a therapeutic agent for a disease associated with angiogenesis or a therapeutic agent for a liver disease. Further, the present invention provides a method for producing an IFN-polymer complex, which comprises mixing IFN and a polymer into which spermine has been introduced in the presence of a metal ion. Furthermore, the present invention provides a method for extending the duration of the pharmacodynamic effect of IFN by using an IFN-high complex. As described above, the IFN-polymer complex of the present invention has a It can be easily obtained by mixing with a spermine-introduced polymer under a metal ion.
  • the spermine used in the present invention is a kind of polyamine having a metal chelating ability and a chemical name of N, N'-bis (3-aminopropyl) -1,4-diaminobtan, and is present in animal fibers and serum. It is a compound and is highly safe for the human body.
  • the polymer used in the present invention may be any polymer that can introduce spermine and is acceptable as a pharmaceutical additive, and is not particularly limited. Polymers and the like can be mentioned, and a water-soluble polymer having a K acid group is suitably used.
  • Example 2 The same operation as in Example 1 was carried out except that pullulan was used instead of dextrin, to obtain a crudely purified aqueous solution of the target complex via a chelate bond between IFN and spermine-pullulane.
  • the reaction product was dialyzed against water for 2 days to remove unreacted DTPA and 4-dimethylaminopyridine, and then freeze-dried to obtain DTP A-introduced pullulan. About 20% mole per mole (electrical conductivity titration method)). Next, the above solution was added to an IFN-] 3 (Mochida Pharmaceutical) aqueous solution of 150,000 single ⁇ 5 / 0.375 ml.
  • IFN-speramine-dextran obtained in Example 1 was diluted with a phosphate buffer and administered to the tail vein at a dose of 100,000 units / kg as IFN administration for 13 days from the day of laser irradiation.
  • 2-5A synthetase is an antiviral enzyme specifically induced by IFN, and it is known that this enzyme activity corresponds to the antiviral activity of IFN.
  • the IFN activity ratio was calculated based on the amount (emission intensity) of 2-5A synthase. Table 2 shows the results.
  • the amount (luminescence intensity) of 2-5A synthetase in the liver when IFN-spermine-pullulane obtained in Example 2 was administered intravenously was determined by IFN alone and IFN-DTP A-Pullulan (Comparative Example 1) was significantly increased compared to intravenous administration, indicating that the IFN-spermine-pullulane complex efficiently targeted IFN activity to the liver. Understand. These effects are achieved by complexing IFN with spermine-introduced pullulan, effectively targeting IFN to its target site, the liver, resulting in enhanced IFN in the liver was done.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Inorganic Chemistry (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne des préparations d'IFN dans lesquelles les IFN sont modifiés de manière à augmenter la stabilité des IFN et à permettre l'exposition de l'efficacité d'un médicament sur un site cible. Un tel complexe de polymères d'interférons peut être obtenu par mélange d'un interféron avec un polymère dans lequel de la spermine a été transférée en présence d'un ion métallique. Comme interféron, on utilise de préférence un interféron β. Comme polymère, on utilise des polymères pharmaceutiquement acceptables tels que des polysaccharides et des polymères alcools polyhydriques hydrosolubles. Comme polysaccharides, on utilise de préférence du pullulan et du dextran. Comme polymère alcool polyhydriques, on utilise de préférence des glycols de polyalkylènes et de l'alcool polyvinylique
PCT/JP2002/003563 2001-04-10 2002-04-10 Complexes de polymeres d'interferons et leur utilisation medicinale WO2002083166A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2001-111320 2001-04-10
JP2001111320 2001-04-10

Publications (1)

Publication Number Publication Date
WO2002083166A1 true WO2002083166A1 (fr) 2002-10-24

Family

ID=18962947

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2002/003563 WO2002083166A1 (fr) 2001-04-10 2002-04-10 Complexes de polymeres d'interferons et leur utilisation medicinale

Country Status (1)

Country Link
WO (1) WO2002083166A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004073701A1 (fr) * 2003-02-19 2004-09-02 Kuniyasu Soda Inhibiteurs de lfa-1 et leur utilisation
US10758623B2 (en) 2013-12-09 2020-09-01 Durect Corporation Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994004696A1 (fr) * 1992-08-25 1994-03-03 Miles Inc. Apport nucleaire de macromolecules facilite par un signal de translocation
EP0593868A1 (fr) * 1992-08-26 1994-04-27 F. Hoffmann-La Roche Ag Conjugués PEG-interféron
WO1996011712A2 (fr) * 1994-10-12 1996-04-25 California Institute Of Technology Vehicules de transfert de genes specifiques des cellules
WO1997035200A1 (fr) * 1996-03-18 1997-09-25 Silica Gel Gmbh Particules superparamagnetiques a relaxivite r1 accrue, leur procede de fabrication et leur utilisation
WO1999036100A2 (fr) * 1998-01-14 1999-07-22 Efrat Biopolymers Ltd. Excipient polymere
WO2001026677A1 (fr) * 1999-10-12 2001-04-19 Santen Pharmaceutical Co., Ltd. Complexe a base d'interferon et son utilisation en medecine

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994004696A1 (fr) * 1992-08-25 1994-03-03 Miles Inc. Apport nucleaire de macromolecules facilite par un signal de translocation
EP0593868A1 (fr) * 1992-08-26 1994-04-27 F. Hoffmann-La Roche Ag Conjugués PEG-interféron
WO1996011712A2 (fr) * 1994-10-12 1996-04-25 California Institute Of Technology Vehicules de transfert de genes specifiques des cellules
WO1997035200A1 (fr) * 1996-03-18 1997-09-25 Silica Gel Gmbh Particules superparamagnetiques a relaxivite r1 accrue, leur procede de fabrication et leur utilisation
WO1999036100A2 (fr) * 1998-01-14 1999-07-22 Efrat Biopolymers Ltd. Excipient polymere
WO2001026677A1 (fr) * 1999-10-12 2001-04-19 Santen Pharmaceutical Co., Ltd. Complexe a base d'interferon et son utilisation en medecine

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004073701A1 (fr) * 2003-02-19 2004-09-02 Kuniyasu Soda Inhibiteurs de lfa-1 et leur utilisation
US10758623B2 (en) 2013-12-09 2020-09-01 Durect Corporation Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same
US11529420B2 (en) 2013-12-09 2022-12-20 Durect Corporation Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same

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