WO2004014350A3 - Polymer conjugates of a local anaesthetic drug - Google Patents

Polymer conjugates of a local anaesthetic drug Download PDF

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Publication number
WO2004014350A3
WO2004014350A3 PCT/GB2003/003525 GB0303525W WO2004014350A3 WO 2004014350 A3 WO2004014350 A3 WO 2004014350A3 GB 0303525 W GB0303525 W GB 0303525W WO 2004014350 A3 WO2004014350 A3 WO 2004014350A3
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
aryl
halogen
hydrogen
hydroxyl
Prior art date
Application number
PCT/GB2003/003525
Other languages
French (fr)
Other versions
WO2004014350A2 (en
Inventor
Jonathan Clark
Original Assignee
Sirus Pharmaceuticals Ltd
Jonathan Clark
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 Sirus Pharmaceuticals Ltd, Jonathan Clark filed Critical Sirus Pharmaceuticals Ltd
Priority to AU2003267542A priority Critical patent/AU2003267542A1/en
Publication of WO2004014350A2 publication Critical patent/WO2004014350A2/en
Publication of WO2004014350A3 publication Critical patent/WO2004014350A3/en

Links

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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/12—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups

Abstract

Thus according to the invention we provide a conjugate of a polymer and a local anaesthetic agent Z characterized in that the agent is an amine of any of the following chemical formulae: wherein R1 and R2 are independently selected from hydrogen, halogen, alkyl and alkyl either groups; X is C=O and Y is NR, or X is NR and Y is C=O, or X is C=O and Y is O, and R is selected from hydrogen, halogen hydroxyl, alkyl, aryl, and acyl; R6 and R7 are independently selected from alkyl, aryl and akylaryl groups; and R8 is selected from hydrogen, halogen, hydroxyl, alkyl, aryl and alkylaryl; or R7 and R8 may be joined, typically through a chain of carbon atoms and, optionally, heteroatoms, to form a ring 5, 6, 7 or 8 atoms in size; n is 0, 1, 2, 3, 4, or 5; and R3, R4 and R5 are each independently selected from hydrogen, hydroxyl, halogen, alkyl, aryl, hydroxyalkyl, hydroxyaryl, aminoalkyl and aminoaryl, with the proviso that at least one of R3, R4 and R5 is a hydroxyl moiety connected to the polymer (P) through a covalent bond. The polymers according to the invention are generally water soluble, although they may not be water soluble at the very large molecular weights, depending on the nature of the further components. Sometimes they form gels. Water soluble polymers are preferred.
PCT/GB2003/003525 2002-08-13 2003-08-13 Polymer conjugates of a local anaesthetic drug WO2004014350A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003267542A AU2003267542A1 (en) 2002-08-13 2003-08-13 Polymer conjugates of a local anaesthetic drug

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0218830.8A GB0218830D0 (en) 2002-08-13 2002-08-13 Anaesthetic conjugate
GB0218830.8 2002-08-13

Publications (2)

Publication Number Publication Date
WO2004014350A2 WO2004014350A2 (en) 2004-02-19
WO2004014350A3 true WO2004014350A3 (en) 2004-10-07

Family

ID=9942247

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2003/003525 WO2004014350A2 (en) 2002-08-13 2003-08-13 Polymer conjugates of a local anaesthetic drug

Country Status (3)

Country Link
AU (1) AU2003267542A1 (en)
GB (1) GB0218830D0 (en)
WO (1) WO2004014350A2 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2003267540A1 (en) * 2002-08-13 2004-02-25 Sirus Pharmaceuticals Ltd Biodegradable polymer
US20100303753A1 (en) * 2007-10-19 2010-12-02 Nektar Therapeutics Oligomer Conjugates of Lidocaine and Its Derivatives
CN106310289B (en) * 2015-06-24 2020-10-13 天津键凯科技有限公司 Conjugate of polyethylene glycol and anesthetic and preparation method thereof
CN107789628B (en) * 2016-12-29 2021-07-23 天津键凯科技有限公司 Application of conjugate of polyethylene glycol and local anesthetic in non-anesthesia analgesia
EP3717017A1 (en) * 2017-12-01 2020-10-07 The Children's Medical Center Corporation Covalent anesthetic-polymer conjugates for prolonged local anesthesia

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2084871A (en) * 1980-09-10 1982-04-21 Johansson Johan Alfred Olof An element containing a therapeutic or palliative agent
US4636387A (en) * 1982-06-21 1987-01-13 Research Corporation Anesthetic polyorganophosphazenes
US4650771A (en) * 1983-11-04 1987-03-17 Miles Laboratories, Inc. Immunogens, antibodies, labeled conjugates, and related derivatives for lidocaine and analogs thereof
WO2002005800A2 (en) * 2000-07-17 2002-01-24 Guilford Pharmaceuticals, Inc. Compositions for sustained release of analgesic agents, and methods of making and using the same
WO2002080979A2 (en) * 2001-03-16 2002-10-17 Fresenius Kabi Deutschland Gmbh Conjugate of hydroxyalkyl starch and an active agent
WO2004014841A1 (en) * 2002-08-13 2004-02-19 Sirus Pharmaceuticals Ltd Compounds, pro-drugs and conjugates derived from mexiletine
WO2004014973A2 (en) * 2002-08-13 2004-02-19 Sirus Pharmaceuticals Ltd Biodegradable polymer

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2084871A (en) * 1980-09-10 1982-04-21 Johansson Johan Alfred Olof An element containing a therapeutic or palliative agent
US4636387A (en) * 1982-06-21 1987-01-13 Research Corporation Anesthetic polyorganophosphazenes
US4650771A (en) * 1983-11-04 1987-03-17 Miles Laboratories, Inc. Immunogens, antibodies, labeled conjugates, and related derivatives for lidocaine and analogs thereof
WO2002005800A2 (en) * 2000-07-17 2002-01-24 Guilford Pharmaceuticals, Inc. Compositions for sustained release of analgesic agents, and methods of making and using the same
WO2002080979A2 (en) * 2001-03-16 2002-10-17 Fresenius Kabi Deutschland Gmbh Conjugate of hydroxyalkyl starch and an active agent
WO2004014841A1 (en) * 2002-08-13 2004-02-19 Sirus Pharmaceuticals Ltd Compounds, pro-drugs and conjugates derived from mexiletine
WO2004014973A2 (en) * 2002-08-13 2004-02-19 Sirus Pharmaceuticals Ltd Biodegradable polymer

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
ARRANZ F ET AL: "ADDUCTS OF SUCCINYLATED DEXTRAN-BENZOCAINE. SYNTHESIS AND CONTROLLED RELEASE BEHAVIOUR", MAKROMOLEKULARE CHEMIE, RAPID COMMUNICATIONS, HUTHIG UND WEPF VERLAG. BASEL, CH, vol. 13, no. 9, 1 September 1992 (1992-09-01), pages 403 - 407, XP000301002 *
BUCKLIN S E ET AL: "THERAPEUTIC EFFICACY OF A POLYMYXIN B-DEXTRAN 70 CONJUGATE IN EXPERIMENTAL MODEL OF ENDOTOXEMIA", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, AMERICAN SOCIETY FOR MICROBIOLOGY, WASHINGTON, DC, US, vol. 39, no. 7, 1 July 1995 (1995-07-01), pages 1462 - 1466, XP000605390, ISSN: 0066-4804 *
COESSENS V ET AL: "Synthesis of polyglutamine and dextran conjugates of streptomycin with an acid-sensitive drug-carrier linkage", JOURNAL OF CONTROLLED RELEASE, ELSEVIER SCIENCE PUBLISHERS B.V. AMSTERDAM, NL, vol. 38, no. 2, 1 February 1996 (1996-02-01), pages 141 - 150, XP004037399, ISSN: 0168-3659 *
GIAMMONA G ET AL: "SYNTHESIS OF MACROMOLECULAR PRODRUGS OF PROCAINE HISTAMINE AND ISONIAZID", CHEMICAL & PHARMACEUTICAL BULLETIN (TOKYO), vol. 37, no. 8, 1989, pages 2245 - 2247, XP002244282, ISSN: 0009-2363 *
GORNER T ET AL: "Lidocaine-loaded biodegradable nanospheres. I. Optimization of the drug incorporation into the polymer matrix", JOURNAL OF CONTROLLED RELEASE, ELSEVIER SCIENCE PUBLISHERS B.V., AMSTERDAM, NL, vol. 57, no. 3, 22 February 1999 (1999-02-22), pages 259 - 268, XP004159028, ISSN: 0168-3659 *
MCLEOD A D ET AL: "GLUCOCORTICIOD-DEXTRAN CONJUGATES AS POTENTIAL PRODRUGS FOR COLON-SPECIFIC DELIVERY: HYDROLYSIS IN RAT GASTROINTESTINAL TRACT CONTENTS.", JOURNAL OF PHARMACEUTICAL SCIENCES, AMERICAN PHARMACEUTICAL ASSOCIATION. WASHINGTON, US, vol. 83, no. 9, 1 September 1994 (1994-09-01), pages 1284 - 1288, XP000465805, ISSN: 0022-3549 *
NOMURA T ET AL: "Pharmacokinetic characteristics and therapeutic effects of mitomycin C-dextran conjugates after intratumoural injection", JOURNAL OF CONTROLLED RELEASE, ELSEVIER SCIENCE PUBLISHERS B.V. AMSTERDAM, NL, vol. 52, no. 3, 31 March 1998 (1998-03-31), pages 239 - 252, XP004115435, ISSN: 0168-3659 *
NURKEEVA ZAURESH S ET AL: "Polymeric complexes of lidocaine hydrochloride with poly(acrylic acid) and poly(2-hydroxyethyl vinyl ether).", JOURNAL OF BIOMATERIALS SCIENCE POLYMER EDITION, vol. 13, no. 7, July 2002 (2002-07-01), pages 759 - 768, XP002244286, ISSN: 0920-5063 *
ROBERT E D ET AL: "ABSENCE OF SUPER SENSITIVITY TO ACETYL CHOLINE IN INNERVATED MUSCLE SUBJECTED TO A PROLONGED PHARMACOLOGIC NERVE BLOCK", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 174, no. 1, 1970, pages 133 - 140, XP008017395, ISSN: 0022-3565 *
SCHERLUND M ET AL: "Nonionic cellulose ethers as potential drug delivery systems for periodontal anesthesia", JOURNAL OF COLLOID AND INTERFACE SCIENCE 15 SEP 2000 UNITED STATES, vol. 229, no. 2, 15 September 2000 (2000-09-15), pages 365 - 374, XP001151860, ISSN: 0021-9797 *
WON C-Y ET AL: "Dextran-estrone conjugate: synthesis and in vitro release study", CARBOHYDRATE POLYMERS, APPLIED SCIENCE PUBLISHERS, LTD. BARKING, GB, vol. 36, no. 4, 1 August 1998 (1998-08-01), pages 327 - 334, XP004145636, ISSN: 0144-8617 *

Also Published As

Publication number Publication date
WO2004014350A2 (en) 2004-02-19
AU2003267542A1 (en) 2004-02-25
AU2003267542A8 (en) 2004-02-25
GB0218830D0 (en) 2002-09-18

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