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WO2005011738A3 - Polymeric conjugates containing phosphine - based chelating groups - Google Patents

Polymeric conjugates containing phosphine - based chelating groups Download PDF

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Publication number
WO2005011738A3
WO2005011738A3 PCT/IT2004/000422 IT2004000422W WO2005011738A3 WO 2005011738 A3 WO2005011738 A3 WO 2005011738A3 IT 2004000422 W IT2004000422 W IT 2004000422W WO 2005011738 A3 WO2005011738 A3 WO 2005011738A3
Authority
WO
WIPO (PCT)
Prior art keywords
chelating
polymers
metal
phosphine
linkers
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/IT2004/000422
Other languages
French (fr)
Other versions
WO2005011738A2 (en
Inventor
Francesco Veronese
Ulderico Mazzi
Gianfranco Pasut
Roberta Visentin
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.)
Universita degli Studi di Padova
Original Assignee
Universita degli Studi di Padova
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 Universita degli Studi di Padova filed Critical Universita degli Studi di Padova
Publication of WO2005011738A2 publication Critical patent/WO2005011738A2/en
Publication of WO2005011738A3 publication Critical patent/WO2005011738A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/06—Macromolecular compounds, carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules
    • A61K51/065—Macromolecular compounds, carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules conjugates with carriers being macromolecules
    • 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
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/12—Macromolecular compounds
    • A61K49/126—Linear polymers, e.g. dextran, inulin, PEG

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)

Abstract

Reactive polymers can be conjugated, directly or by means of linkers and/or others polymers to chelating agents comprising at least one phosphorous atom in the form of a phosphine or phosphine oxide (or precursors thereof) to form conjugates useful in diagnostic and therapeutic applications. In particular this invention provides conjugates comprising a hydrophilic polymer bound, directly or by means of other moieties, to at least one chelating group able to chelate metal radioisotopes comprising at least one phosphine or one phosphine oxide phosphorous. Such chelating groups can be conjugated to the hydrophilic polymer directly or via one or more linkers and/or one or more additional polymers. The use of additional polymers can provide increased loading of chelating agent. The linkers are preferably selected among alkyl groups or aromatic groups or cleavable peptides or other biodegradable sequences. Additionally, one or more targeting molecules can be linked to the hydrophilic polymer directly or by means of linkers and/or others polymers. Due to their polymeric structure, the conjugates according to the invention have enhanced specificity toward certain tissues, such as tumors, inflamed tissued and the liver. The specificity can be further increased by the additional provision of targeting moieties such as antibodies or sugars. These conjugates can be formulated for remaining in the blood circulation for a period for time suitable for diagnostic and therapeutic applications. Moreover they possess thermodynamic and kinetic stability, keeping the metal chelate intact under physiological conditions. The invention also provides a very simple and efficient method for the labelling of radiopharmaceuticals, which avoids the use of any additional reducing agent. Accordingly, metal ions like technetium or rhenium can be added as pertechnetate or pherrhenate to chelating agents comprising polymer and a phosphine and surprisingly it has been found that such chelating agents can act as reducing agents of the metal and the use of an additional reducing agent is not necessary. This allows the preparation of simple kits comprising a component (a) comprising the polymeric chelating agent and a component (b) comprising the metal ion in its highest oxidation state. These two components can be kept separately and combined together just before use to yield the metal complex without the need of further reducing step and purification.
PCT/IT2004/000422 2003-07-31 2004-07-29 Polymeric conjugates containing phosphine - based chelating groups Ceased WO2005011738A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT2003PD000174A ITPD20030174A1 (en) 2003-07-31 2003-07-31 POLYMERIC CONJUGATES FOR DIAGNOSTICS AND THERAPY
ITPD2003A000174 2003-07-31

Publications (2)

Publication Number Publication Date
WO2005011738A2 WO2005011738A2 (en) 2005-02-10
WO2005011738A3 true WO2005011738A3 (en) 2005-04-14

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IT2004/000422 Ceased WO2005011738A2 (en) 2003-07-31 2004-07-29 Polymeric conjugates containing phosphine - based chelating groups

Country Status (2)

Country Link
IT (1) ITPD20030174A1 (en)
WO (1) WO2005011738A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0804406D0 (en) * 2008-03-10 2008-04-16 Univ Zuerich Metal complexes
WO2011125331A1 (en) * 2010-04-06 2011-10-13 株式会社Ihi Metal salen complex derivative and process for production thereof
JP2017509587A (en) 2013-12-27 2017-04-06 ノーバス・インターナショナル・インコーポレイテッドＮｏｖｕｓ Ｉｎｔｅｒｎａｔｉｏｎａｌ，Ｉｎｃ． Ethoxylated surfactant
US10584306B2 (en) 2017-08-11 2020-03-10 Board Of Regents Of The University Of Oklahoma Surfactant microemulsions

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0277088A2 (en) * 1987-01-19 1988-08-03 Schering Aktiengesellschaft Polymer complexes, process for their preparation and pharmaceutical compounds containing them
WO1991018630A1 (en) * 1990-05-30 1991-12-12 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Polyether-substituted tumor agents
EP0481526A1 (en) * 1989-04-07 1992-04-22 Nycomed Salutar, Inc. Chelants
US5155215A (en) * 1985-11-18 1992-10-13 Access Pharmaceuticals Inc. Polychelating agents for image and spectral enhancement (and spectral shift)
US5900228A (en) * 1996-07-31 1999-05-04 California Institute Of Technology Bifunctional detection agents having a polymer covalently linked to an MRI agent and an optical dye
WO2001019838A1 (en) * 1999-09-13 2001-03-22 Du Pont Pharmaceuticals Company Macrocyclic chelants for metallopharmaceuticals
WO2003014157A2 (en) * 2001-08-03 2003-02-20 Bracco Imaging S.P.A. Peptides conjugates, their derivatives with metal complexes and use thereof for magnetic resonance imaging (mri)
WO2004010868A2 (en) * 2002-07-31 2004-02-05 General Electric Company Method for binding molecular agents to angiogencic blood vessels

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5155215A (en) * 1985-11-18 1992-10-13 Access Pharmaceuticals Inc. Polychelating agents for image and spectral enhancement (and spectral shift)
EP0277088A2 (en) * 1987-01-19 1988-08-03 Schering Aktiengesellschaft Polymer complexes, process for their preparation and pharmaceutical compounds containing them
EP0481526A1 (en) * 1989-04-07 1992-04-22 Nycomed Salutar, Inc. Chelants
WO1991018630A1 (en) * 1990-05-30 1991-12-12 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Polyether-substituted tumor agents
US5900228A (en) * 1996-07-31 1999-05-04 California Institute Of Technology Bifunctional detection agents having a polymer covalently linked to an MRI agent and an optical dye
WO2001019838A1 (en) * 1999-09-13 2001-03-22 Du Pont Pharmaceuticals Company Macrocyclic chelants for metallopharmaceuticals
WO2003014157A2 (en) * 2001-08-03 2003-02-20 Bracco Imaging S.P.A. Peptides conjugates, their derivatives with metal complexes and use thereof for magnetic resonance imaging (mri)
WO2004010868A2 (en) * 2002-07-31 2004-02-05 General Electric Company Method for binding molecular agents to angiogencic blood vessels

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
"UNITA? DI RICERCA DI PADOVA, Sezione Radiofarmaci", CIRC MSB, UNITÀ AFFERENTI, UNIVERSITÀ DEGLI STUDI DI PADOVA, ATTIVITÀ ANNO 2002, 2002, pages 1 - 26, XP002312000, Retrieved from the Internet <URL:http://www.circmsb.uniba.it/rel2002/UNITA%20padova.pdf> *
BERGBREITER D E ET AL: "Tridentate SCS palladium(II) complexes: New, highly stable, recyclable catalysts for the heck reaction", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 1999 UNITED STATES, vol. 121, no. 41, 1999, pages 9531 - 9538, XP002312003, ISSN: 0002-7863 *
HARWIG C W ET AL: "Soluble polymers: New options in both traditional and combinatorial synthesis", CHEMTRACTS, vol. 12, no. 1, 1999, pages 1 - 26, XP008038355, ISSN: 1431-9268 *
JAN KOTEK ET AL.: "Lanthanide(III) Complexes of Novel Mixed Carboxylic-Phosphorus Acid Derivatives of Diethylenetriamine: A Step towards More Efficient MRI Contrast Agents", CHEM. EUR. J., vol. 9, no. 23, 5 December 2003 (2003-12-05), pages 5899 - 5915, XP002312001 *
KÖLLHOFER AXEL ET AL: "Homogeneous catalysts supported on soluble polymers: biphasic Sonogashira coupling of aryl halides and acetylenes using MeOPEG-bound phosphine-palladium catalysts for efficient catalyst recycling.", CHEMISTRY (WEINHEIM AN DER BERGSTRASSE, GERMANY) 17 MAR 2003, vol. 9, no. 6, 17 March 2003 (2003-03-17), pages 1416 - 1425, XP002312002, ISSN: 0947-6539 *
MATTHEWS S E ET AL: "Macromolecular systems for chemotherapy and magnetic resonance Imaging", ADVANCED DRUG DELIVERY REVIEWS 1996 NETHERLANDS, vol. 18, no. 2, 1996, pages 219 - 267, XP002311999, ISSN: 0169-409X *
SIEBER F ET AL: "DEVELOPMENT AND APPLICATION OF A POLY(ETHYLENE GLYCOL)-SUPPORTED TRIARYLPHOSPHINE REAGENT: EXPANDING THE SPHERE OF LIQUID-PHASE ORGANIC SYNTHESIS", JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, US, vol. 64, no. 14, 9 July 1999 (1999-07-09), pages 5188 - 5192, XP000830433, ISSN: 0022-3263 *
UOZUMI Y ET AL: "New Amphiphilic Palladium-Phosphine Complexes Bound to Solid Supports: Preparation and Use for Catalytic Allylic Substitution in Aqueous Media", TETRAHEDRON LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 38, no. 20, 19 May 1997 (1997-05-19), pages 3557 - 3560, XP004061958, ISSN: 0040-4039 *
VISENTIN R ET AL: "99mtechnetium labeling of pegylated PN2S ligand in presence or absence of Tin(II).", JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, vol. 46, no. Supplement 1, August 2003 (2003-08-01), & 15TH INTERNATIONAL SYMPOSIUM ON RADIOPHARMACEUTICAL CHEMISTRY; SYDNEY, AUSTRALIA; AUGUST 10-14, 2003, pages S26, XP002311998, ISSN: 0362-4803 *

Also Published As

Publication number Publication date
ITPD20030174A1 (en) 2003-10-29
WO2005011738A2 (en) 2005-02-10

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