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WO2004082585A3 - Water-soluble conjugates of phenytoin - Google Patents

Water-soluble conjugates of phenytoin Download PDF

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Publication number
WO2004082585A3
WO2004082585A3 PCT/GB2004/000631 GB2004000631W WO2004082585A3 WO 2004082585 A3 WO2004082585 A3 WO 2004082585A3 GB 2004000631 W GB2004000631 W GB 2004000631W WO 2004082585 A3 WO2004082585 A3 WO 2004082585A3
Authority
WO
WIPO (PCT)
Prior art keywords
drug
acid
phenytoin
peg
polymers
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/GB2004/000631
Other languages
French (fr)
Other versions
WO2004082585A2 (en
Inventor
Jonathan Clark
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.)
SIRUS PHARMACEUTICALS Ltd
Original Assignee
SIRUS PHARMACEUTICALS 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
Priority claimed from GB0306445A external-priority patent/GB0306445D0/en
Priority claimed from PCT/GB2003/003522 external-priority patent/WO2004014973A2/en
Application filed by SIRUS PHARMACEUTICALS Ltd filed Critical SIRUS PHARMACEUTICALS Ltd
Publication of WO2004082585A2 publication Critical patent/WO2004082585A2/en
Publication of WO2004082585A3 publication Critical patent/WO2004082585A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
    • C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
    • C08G73/10—Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors
    • C08G73/1092—Polysuccinimides
    • 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
    • A61P23/00—Anaesthetics
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Polymers & Plastics (AREA)
  • Anesthesiology (AREA)
  • Medicinal Preparation (AREA)
  • Polyethers (AREA)

Abstract

The present invention relates to conjugates of phenytoin with water-soluble polymers, having improved solubilityand absorption characteristics. Examples of polymers to.which phenytoin or a pro-drug thereof may be attached include natural polymers such as dextran, dextrin or a synthetic polymer, preferably biodegradable and non-toxic in nature. The drug is connected either directly to the polymer or (more preferably) through a linker which may be a peptide, amino acid, a short carbon chain such as succinic acid, 6-aminohexanoic acid, 5-aminopentanoic acid, 4-aminobutanoic acid, 3-aminopropanoic acid or other similar linker. Suitable groups are those derived from polyethylene glycol (PEG) acids. For example PEG may be condensed with a diacid e.g. succinic acid to yield a PEG derivative bearing an acyl group (or two acyl groups) to which the drug may be attached. Examples of PEG conjugates according to this invention are as in Formulae (I), (II), (III); where ”Drug-O” indicates phenytoin or a pro-drug thereof, Ra is hydrogen, alkyl, aryl or alkylaryl and m is 0 or an integer of up to 1000, preferably 1 to 1000, more preferably 5 to 1000, particularly 10 to 500. Preferably Ra represents Coalkyl, e.g. COMe. Ra may also represent COCH2CH2COO-Drug.
PCT/GB2004/000631 2003-03-20 2004-02-17 Water-soluble conjugates of phenytoin Ceased WO2004082585A2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0306445A GB0306445D0 (en) 2003-03-20 2003-03-20 Conjugate
GB0306445.8 2003-03-20
PCT/GB2003/003522 WO2004014973A2 (en) 2002-08-13 2003-08-13 Biodegradable polymer

Publications (2)

Publication Number Publication Date
WO2004082585A2 WO2004082585A2 (en) 2004-09-30
WO2004082585A3 true WO2004082585A3 (en) 2005-07-14

Family

ID=33031403

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2004/000631 Ceased WO2004082585A2 (en) 2003-03-20 2004-02-17 Water-soluble conjugates of phenytoin

Country Status (1)

Country Link
WO (1) WO2004082585A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4991037B2 (en) 2004-04-01 2012-08-01 カーディオム ファーマ コーポレイション Drug conjugates comprising ion channel modulating compounds
CA2561819A1 (en) * 2004-04-01 2005-12-01 Cardiome Pharma Corp. Prodrugs of ion channel modulating compounds and uses thereof
WO2012082995A1 (en) * 2010-12-15 2012-06-21 Nektar Therapeutics Oligomer-containing hydantoin compounds
CN113773256B (en) * 2021-09-16 2022-11-18 精华制药集团南通有限公司 Synthesis method of amber

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4280995A (en) * 1979-12-31 1981-07-28 Pharmaceutical Associates, Inc. Oral suspension of phenytoin
US4801504A (en) * 1985-03-18 1989-01-31 Eastman Kodak Company Fluorescent labels having a polysaccharide bound to polymeric particles
WO2004014973A2 (en) * 2002-08-13 2004-02-19 Sirus Pharmaceuticals Ltd Biodegradable polymer

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4280995A (en) * 1979-12-31 1981-07-28 Pharmaceutical Associates, Inc. Oral suspension of phenytoin
US4801504A (en) * 1985-03-18 1989-01-31 Eastman Kodak Company Fluorescent labels having a polysaccharide bound to polymeric particles
WO2004014973A2 (en) * 2002-08-13 2004-02-19 Sirus Pharmaceuticals Ltd Biodegradable polymer

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Vidal 1998, Le Dictionnaire, 74e ÉDITION", 1998, EDITION DU VIDAL, PARIS, FR, XP002287050 *
MULLER D G ET AL: "Factors influencing the precipitation time of phenytoin in the presence of DDMS, one of its prodrugs", INTERNATIONAL JOURNAL OF PHARMACEUTICS 1991 NETHERLANDS, vol. 75, no. 2-3, 1991, pages 201 - 209, XP002287049, ISSN: 0378-5173 *

Also Published As

Publication number Publication date
WO2004082585A2 (en) 2004-09-30

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