DK2355853T3 - Bionedbrydelige polymer-bioaktivt fragmentkonjugater - Google Patents

Bionedbrydelige polymer-bioaktivt fragmentkonjugater Download PDF

Info

Publication number
DK2355853T3
DK2355853T3 DK09818693.5T DK09818693T DK2355853T3 DK 2355853 T3 DK2355853 T3 DK 2355853T3 DK 09818693 T DK09818693 T DK 09818693T DK 2355853 T3 DK2355853 T3 DK 2355853T3
Authority
DK
Denmark
Prior art keywords
bioactive
polymer
moiety
monomer
biodegradable polymer
Prior art date
Application number
DK09818693.5T
Other languages
English (en)
Inventor
Michael Shane O'shea
Florian Hans Maximilian Graichen
Russell John Tait
Heng Chy Taing
Justine Leigh Jeffery
Original Assignee
Polyactiva Pty 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 AU2008905263A external-priority patent/AU2008905263A0/en
Application filed by Polyactiva Pty Ltd filed Critical Polyactiva Pty Ltd
Application granted granted Critical
Publication of DK2355853T3 publication Critical patent/DK2355853T3/da

Links

Classifications

    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • 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
    • 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
    • A61K31/13—Amines
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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
    • 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
    • A61K47/593—Polyesters, e.g. PLGA or polylactide-co-glycolide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/30—Low-molecular-weight compounds
    • C08G18/34—Carboxylic acids; Esters thereof with monohydroxyl compounds
    • 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
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/30—Low-molecular-weight compounds
    • C08G18/38—Low-molecular-weight compounds having heteroatoms other than oxygen
    • C08G18/3819—Low-molecular-weight compounds having heteroatoms other than oxygen having nitrogen
    • C08G18/3842—Low-molecular-weight compounds having heteroatoms other than oxygen having nitrogen containing heterocyclic rings having at least one nitrogen atom in the ring
    • C08G18/3848—Low-molecular-weight compounds having heteroatoms other than oxygen having nitrogen containing heterocyclic rings having at least one nitrogen atom in the ring containing two nitrogen atoms in the ring
    • 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
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
    • C08G18/4269—Lactones
    • C08G18/4277—Caprolactone and/or substituted caprolactone
    • 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
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
    • C08G18/428—Lactides
    • 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
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • C08G18/73—Polyisocyanates or polyisothiocyanates acyclic
    • 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
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • C08G18/77—Polyisocyanates or polyisothiocyanates having heteroatoms in addition to the isocyanate or isothiocyanate nitrogen and oxygen or sulfur
    • C08G18/771—Polyisocyanates or polyisothiocyanates having heteroatoms in addition to the isocyanate or isothiocyanate nitrogen and oxygen or sulfur oxygen
    • 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
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
    • C08G63/12—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from polycarboxylic acids and polyhydroxy compounds
    • C08G63/16—Dicarboxylic acids and dihydroxy compounds
    • 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
    • C08G67/00—Macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing oxygen or oxygen and carbon, not provided for in groups C08G2/00 - C08G65/00
    • C08G67/04—Polyanhydrides
    • 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
    • C08G2230/00—Compositions for preparing biodegradable polymers

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Polymers & Plastics (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Anesthesiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Emergency Medicine (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Medicinal Preparation (AREA)
  • Polyurethanes Or Polyureas (AREA)
  • Materials For Medical Uses (AREA)
  • Polyesters Or Polycarbonates (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Biological Depolymerization Polymers (AREA)
  • Dental Preparations (AREA)

Claims (20)

1. Bionedbrydelig polymer omfattende en flerhed af frigivelige bioaktive fragmenter, hvor de frigivelige bioaktive fragmenter er vedhængende fra og kovalent bundet til det bionedbrydelige polymerskelet, hvor den bionedbrydelige polymer har en generel formel (I):
(I) hvor: A og B, der er det samme eller forskellige, repræsenterer det resterende af polymerskelettet og (i) omfatter en eller flere -X-R(ZD)-Y- som vist i formel (I), og (ii) er hver dannet af monomerenheder der er koblet via et bionedbrydeligt fragment, hvor hver X, Y, R, Z og D i et givet -X-R(ZD)-Y- fragment af den bionedbrydelige polymer er det samme eller forskellige; X og Y er hver uafhængigt et bionedbrydeligt fragment valgt fra et estereller karbamatfragment; R repræsenterer et lineært eller forgrenet eventuelt substitueret carbonhydrid; Z er et spacerfragment; og D er et frigiveligt bioaktivt fragment valgt fra fluoroquinolon antibiotika, hvor de bioaktive fragmenter (D) er i stand til at blive frigivet ved en hastighed lig med eller hurtigere end hastigheden af bionedbrydning af polymerskelettet.
2. Den bionedbrydelige polymer ifølge krav 1, hvor de bioaktive fragmenter (D) er valgt fra alatrofloxacin, balofloxacin, ciprofloxacin, clinafloxacin, danofoxacin, delafloxacin, dextrofloxacin, difloxacin, enoxacin, enrofloxacin, garenoxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, lomefloxacin, marbofloxacin, moxifloxacin, nadifloxacin, norfloxacin, ofloxacin, orbifloxacin, pefloxacin, sitafloxacin, sparfloxacin, temafloxacin, tosufloxacin, tosulfloxacin og trovafloxacin.
3. Den bionedbrydelige polymer ifølge krav 1 eller krav 2, hvor A og B er valgt fra polyurethaner, polyestere, og copolymerer deraf.
4. Den bionedbrydelige polymer ifølge et hvilket som helst af kravene 1 til 3, hvilken omfatter mindre end 25 mol% af polymeriserede rester der er afledt fra en C2-diol, i forhold til det samlede antal mol af polymeriserede diolrester.
5. Den bionedbrydelige polymer ifølge et hvilket som helst af kravene 1 til 4, hvor D er koblet via Z til R af et ester-, amid-, thiol-, anhydrid-, imid-, karbonat-, peroxid-, peroxyester-, fosfatester-, thioester-, sulfatester-, karbamat-, azo- eller boronatesterfragment.
6. Den bionedbrydelige polymer ifølge krav 5, hvor Z er valgt fra gruppen bestående af oxy (-0-), alkyl, alkenyl, alkynyl, aryl, acyl (including -C(O)-), carbocyclyl, heterocyclyl, heteroaryl, alkyloxy, alkenyloxy, alkynyloxy, aryloxy, acyloxy, carbocyclyloxy, heterocyclyloxy, heteroaryloxy, alkylthio, alkenylthio, alkynylthio, arylthio, acylthio, carbocyclylthio, heterocyclylthio, heteroarylthio, alkylalkenyl, alkylalkynyl, alkylaryl, alkylacyl, alkylcarbocyclyl, alkylheterocyclyl, alkylheteroaryl, alkyloxyalkyl, alkenyloxyalkyl, alkynyloxyalkyl, aryloxyalkyl, alkylacyloxy, alkyloxyacylalkyl, alkylcarbocyclyloxy, alkylheterocyclyloxy, alkylheteroaryloxy, alkylthioalkyl, alkenylthioalkyl, alkynylthioalkyl, arylthioalkyl, alkylacylthio, alkylcarbocyclylthio, alkylheterocyclylthio, alkylheteroarylthio, alkylalkenylalkyl, alkylalkynylalkyl, alkylarylalkyl, alkylacylalkyl, arylalkylaryl, arylalkenylaryl, arylalkynylaryl, arylacylaryl, arylacyl, arylcarbocyclyl, arylheterocyclyl, arylheteroaryl, alkenyloxyaryl, alkynyloxyaryl, aryloxyaryl, arylacyloxy, arylcarbocyclyloxy, arylheterocyclyloxy, arylheteroaryloxy, alkylthioaryl, alkenylthioaryl, alkynylthioaryl, arylthioaryl, arylacylthio, arylcarbocyclylthio, arylheterocyclylthio, og arylheteroarylthio, hvor når til stede den eller hver -CH2-gruppe i en hvilken som helst alkylkæde kan erstattes afen divalentgruppe uafhængigt valgt fra -O-, -0P(0)2-, -0P(0)20- -S-, -S(O)-, -S(0)20-, -0S(0)20-, -N = N-, -0Si(0Ra)20-, -Si(0Ra)20-, -0B(0Ra)0-, -B(0Ra)0-, -NRa-, -C(O)-, -C(0)0-, -0C(0)0-, -0C(0)NRa- og -C(0)NRa-, hvor den eller hver Ra kan være uafhængigt valgt fra hydrogen, alkyl, alkenyl, alkynyl, aryl, carbocyclyl, heteroaryl, heterocyclyl, arylalkyl, og acyl.
7. Den bionedbrydelige polymer ifølge krav 5 eller krav 6, hvor Z er valgt fra -O-; -C(O)-; og eventuelt substitueret: -0C(0)-Ci-i8alkylen-C(0)-; -C(0)0-Ci-i8alkylen-C(0)-; -NRaC(0)-Ci-i8alkylen-C(0)-; -C(0)0-Ci-i8alkylen-0-; -O-Ci-lealkylen-O-; -O-Ci-isalkylen-NR3-; -0C(0)-Ci-i8alkylen-NRa-; -C(0)-Ci-i8alkylen-NRa-; -0C(0)-Ci-i8alkylen-0-; -C(0)-Ci-i8alkylen-0-; og -C(0)NRa-Ci-i8alkylen-NRa- hvor Ra er valgt fra hydrogen, Ci-isalkyl, Ci-isalkenyl, Ci-isalkynyl, C6-isaryl, C3-i8carbocyclyl, C3-isheteroaryl, C3-i8heterocyclyl, og C7-isarylalkyl.
8. Den bionedbrydelige polymer ifølge et hvilket som helst af kravene 5 til 7, hvor Z er valgt fra -O-; -C(O)-; og -0C(0)-Ci-i8alkylen-C(0)-, såsom -0C(0)-C2-3alkylen-C(0)-.
9. Den bionedbrydelige polymer ifølge et hvilket som helst af kravene 1 til 8, hvor R er et lineært eller forgrenet eventuelt substitueret carbonhydrid med fra 1 til 12 kulstofatomer.
10. Den bionedbrydelige polymer ifølge et hvilket som helst af kravene 1 til 9, hvor R er aromatisk.
11. Den bionedbrydelige polymer ifølge krav 6, hvor, Z er aryloxy.
12. Den bionedbrydelige polymer ifølge krav 6, hvor Z er arylacyloxy.
13. Den bionedbrydelige polymer ifølge et hvilket som helst af kravene 1 til 10, opnåelig ved polymerisering af et monomer-bioaktivt fragmentkonjugat af formel (II):
(Π) hvor: X' og V er hver uafhængige funktionelle grupper der (a) er i stand til at undergå polymerisering med monomer med kompatibel kemisk funktionalitet, og (b) reagere med den kompatible kemiske funktionalitet for at give et bionedbrydeligt fragment, hvor X' og V er hver uafhængigt valgt fra hydroxyl, carboxylsyre, isocyanat, og carboxylsyrehalid; R repræsenterer et lineært eller forgrenet eventuelt substitueret carbonhydrid; Z er et spacerfragment; og D er et frigiveligt bioaktivt fragment valgt fra fluoroquinolon antibiotika; med mindst en monomer omfattende kompatibel kemisk funktionalitet.
14. Bionedbrydelig polymer ifølge krav 13, opnåelig ved polymerisering af det monomer-bioaktivt fragmentkonjugat af formel II, hvor substituenterne X' og Y' er hver hydroxyl, med et diisocyanat frembringende en polyurethan.
15. Bionedbrydelig polymer ifølge krav 13, opnåelig ved polymerisering af det monomer-bioaktive fragmentkonjugat af formel (II) hvor X' og Y' er hver hydroxyl med et polyisocyanat, en polysyre eller polyester, der kan finde sted i tilstedeværelsen af en eller flere andre typer af polyoler.
16. Bionedbrydelig polymer ifølge krav 15, hvor den ene eller flere andre typer af polyoler er polyesterpolyoler.
17. Bionedbrydelig polymer ifølge krav 15 eller krav 16, hvor polyisocyanatet er valgt fra m-phenylen diisocyanat, p-phenylen diisocyanat, 2,4-toluen diisocyanat, 2,6-toluen diisocyanat, 1,6-hexamethylen diisocyanat, 1,4-hexamethylen diisocyanat, 1,3-cyclohexan diisocyanat, 1,4-cyclohexan diisocyanat, hexahydro-toluen diisocyanat og dets isomerer, isophoron diisocyanat, dicyclo-hexylmethan diisocyanater, 1,5-napthylen diisocyanat, 4,4'-diphenylmethan diisocyanat, 2,4' diphenylmethan diisocyanat, 4,4'-biphenylen diisocyanat, 3,3'-dimethoxy-4,4'-biphenylen diisocyanat, 3,3'-dimethyl-diphenylpropan-4,4'-diisocyanat, 2,4,6-toluen triisocyanat, 4,4'-dimethyl-diphenylmethan-2,2',5,5,-tetraisocyanat, polymethylen polyphenyl-polyisocyanater og alkylestere af lysin diisocyanat.
18. Fremgangsmåde til at fremstille en bionedbrydelig polymer ifølge et hvilket som helst af kravene valgt fra 1 til 10 og 13 til 16, hvilken fremgangsmåde omfatter trinnet at polymerisere et monomer-bioaktivt fragmentkonjugat af formel (II):
(Π) hvor: X' og V er hver uafhængige funktionelle grupper der (a) er i stand til at undergå polymerisering med monomer med kompatibel kemisk funktionalitet, og (b) reagere med den kompatible kemiske funktionalitet for at give et bionedbrydeligt fragment, hvor X' og V er hver uafhængigt valgt fra hydroxyl, carboxylsyre, isocyanat, og carboxylsyrehalid; og R, Z og D er som defineret i et hvilket som helst af kravene valgt fra 1 til 10 og 13 til 17; med mindst en monomer omfattende kompatibel kemisk funktionalitet.
19. Monomer-bioaktivt fragmentkonjugat der er egnet til anvendelse i fremstilling af en bionedbrydelig polymer, hvor det monomer-bioaktive fragmentkonjugat har en struktur af general formel (II):
(Π) hvor: X' og V er hver uafhængige funktionelle grupper der (a) er i stand til at undergå polymerisering med monomer med kompatibel kemisk funktionalitet for at danne en bionedbrydelig polymer, og (b) reagere med den kompatible kemiske funktionalitet for at give et bionedbrydeligt fragment, hvor X' og V er hver hydroxyl og den kompatible kemiske funktionalitet er et diisocyanat og frembringer en polyurethan; R repræsenterer et lineært eller forgrenet eventuelt substitueret carbonhydrid; Z er et spacerfragment; og D er valgt fra fluoroquinolon antibiotika.
20. Monomer-bioaktivt fragmentkonjugat ifølge krav 19, hvor de bioaktive fragmenter (D) er valgt fra alatrofloxacin, balofloxacin, ciprofloxacin, clinafloxacin, danofoxacin, delafloxacin, dextrofloxacin, difloxacin, enoxacin, enrofloxacin, garenoxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, lomefloxacin, marbofloxacin, moxifloxacin, nadifloxacin, norfloxacin, ofloxacin, orbifloxacin, pefloxacin, sitafloxacin, sparfloxacin, temafloxacin, tosufloxacin, tosulfloxacin og trovafloxacin.
DK09818693.5T 2008-10-10 2009-10-09 Bionedbrydelige polymer-bioaktivt fragmentkonjugater DK2355853T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2008905263A AU2008905263A0 (en) 2008-10-10 Drug polymer conjugates
PCT/AU2009/001342 WO2010040188A1 (en) 2008-10-10 2009-10-09 Biodegradable polymer - bioactive moiety conjugates

Publications (1)

Publication Number Publication Date
DK2355853T3 true DK2355853T3 (da) 2017-03-06

Family

ID=42100154

Family Applications (1)

Application Number Title Priority Date Filing Date
DK09818693.5T DK2355853T3 (da) 2008-10-10 2009-10-09 Bionedbrydelige polymer-bioaktivt fragmentkonjugater

Country Status (17)

Country Link
EP (1) EP2355853B1 (da)
JP (2) JP5746629B2 (da)
KR (1) KR101726715B1 (da)
CN (1) CN102245214B (da)
AU (1) AU2009301646B2 (da)
CA (2) CA2739078C (da)
DK (1) DK2355853T3 (da)
ES (1) ES2617913T3 (da)
HU (1) HUE030895T2 (da)
IL (2) IL212053A (da)
MY (1) MY155629A (da)
NZ (2) NZ603964A (da)
PT (1) PT2355853T (da)
SG (1) SG195531A1 (da)
SI (1) SI2355853T1 (da)
WO (1) WO2010040188A1 (da)
ZA (1) ZA201102501B (da)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI2340271T1 (sl) * 2008-10-10 2019-08-30 Polyactiva Pty Ltd. Konjugati polimer-bioaktivnega sredstva
US8889193B2 (en) 2010-02-25 2014-11-18 The Johns Hopkins University Sustained delivery of therapeutic agents to an eye compartment
WO2011141341A1 (en) 2010-05-14 2011-11-17 Iberhospitex, S.A. Compounds for the synthesis of biostable polyurethane, polyurea or polyurea urethane polymers
EP2590605A1 (en) 2010-07-09 2013-05-15 Board of Regents of the University of Texas System Biodegradable scaffolds
WO2012039979A2 (en) 2010-09-10 2012-03-29 The Johns Hopkins University Rapid diffusion of large polymeric nanoparticles in the mammalian brain
US9327037B2 (en) 2011-02-08 2016-05-03 The Johns Hopkins University Mucus penetrating gene carriers
CA2863632C (en) 2012-01-19 2017-07-11 The Johns Hopkins University Nanoparticle formulations with enhanced mucosal penetration
US9593201B2 (en) 2012-03-01 2017-03-14 The University Of Akron Biodegradable polymers with pendant functional groups attached through amide bonds
EP2825206A1 (en) 2012-03-16 2015-01-21 The Johns Hopkins University Controlled release formulations for the delivery of hif-1 inhibitors
US10159743B2 (en) * 2012-03-16 2018-12-25 The Johns Hopkins University Non-linear multiblock copolymer-drug conjugates for the delivery of active agents
US9827191B2 (en) 2012-05-03 2017-11-28 The Johns Hopkins University Compositions and methods for ophthalmic and/or other applications
WO2013166408A1 (en) 2012-05-03 2013-11-07 Kala Pharmaceuticals, Inc. Pharmaceutical nanoparticles showing improved mucosal transport
EP2844295A1 (en) 2012-05-03 2015-03-11 Kala Pharmaceuticals, Inc. Pharmaceutical nanoparticles showing improved mucosal transport
US11596599B2 (en) 2012-05-03 2023-03-07 The Johns Hopkins University Compositions and methods for ophthalmic and/or other applications
JP6392209B2 (ja) 2012-05-04 2018-09-19 ザ・ジョンズ・ホプキンス・ユニバーシティー 粘液内層を通過する迅速な透過のための脂質ベース薬物キャリア
PT2863921T (pt) * 2012-06-26 2018-07-17 Polyactiva Pty Ltd Conjugado de polímero-aine
CN102827035A (zh) * 2012-08-21 2012-12-19 江苏恒祥化工有限责任公司 一种1,4-环己烷二异氰酸酯的合成方法
US10568975B2 (en) 2013-02-05 2020-02-25 The Johns Hopkins University Nanoparticles for magnetic resonance imaging tracking and methods of making and using thereof
MX2015011874A (es) * 2013-03-08 2016-01-25 Polyactiva Pty Ltd Conjugado de polimero para la administracion de un agente bioactivo.
US10113033B2 (en) 2013-03-08 2018-10-30 Polyactiva Pty Ltd Polymer conjugate for delivery of a bioactive agent
EP3357522B1 (en) * 2013-03-15 2019-10-16 Interface Biologics Inc. Coated medical article for drug release
US9572832B2 (en) * 2013-08-29 2017-02-21 Holy Stone Healthcare Co., Ltd. Compound of glycosaminoglycan and its fabrication method as well as application
WO2015127389A1 (en) 2014-02-23 2015-08-27 The Johns Hopkins University Hypotonic enema formulations and methods of use
US10335500B2 (en) 2014-05-12 2019-07-02 The Johns Hopkins University Highly stable biodegradable gene vector platforms for overcoming biological barriers
CN104004001B (zh) * 2014-05-28 2016-03-30 苏州大学 含双硫五元环功能基团的环状碳酸酯单体及其制备方法
CN104031248B (zh) * 2014-05-28 2016-09-07 博瑞生物医药（苏州）股份有限公司 侧链含双硫五元环功能基团的碳酸酯聚合物及其应用
CN105770900B (zh) * 2014-05-28 2018-11-02 博瑞生物医药（苏州）股份有限公司 侧链含双硫五元环功能基团的碳酸酯聚合物的应用
US9359316B1 (en) * 2014-11-25 2016-06-07 Concentric Analgesics, Inc. Prodrugs of phenolic TRPV1 agonists
US11634384B2 (en) 2014-11-25 2023-04-25 Concentric Analgesics, Inc. Prodrugs of phenolic TRPV1 agonists
CA2974715C (en) 2015-01-27 2020-05-05 The Johns Hopkins University Hypotonic hydrogel formulations for enhanced transport of active agents at mucosal surfaces
NZ741132A (en) * 2015-09-11 2022-09-30 Polyactiva Pty Ltd Polymer conjugate comprising a bioactive agent
CN116942677A (zh) 2015-09-21 2023-10-27 梯瓦制药国际有限责任公司 缓释奥氮平制剂
WO2017205534A1 (en) 2016-05-25 2017-11-30 Concentric Analgesics, Inc. Prodrugs of phenolic trpv1 agonists in combination with local anesthetics and vasoconstrictors for improved local anesthesia
CN108532126B (zh) * 2017-03-02 2021-04-16 江苏华龙无纺布有限公司 一种抗菌性生物可降解聚酯无纺布及制备方法
US11207417B2 (en) 2017-03-14 2021-12-28 Polyactiva Pty Ltd Drug-polymer conjugate
CN110461336A (zh) 2017-03-14 2019-11-15 波利艾克蒂瓦有限公司 药物-聚合物缀合物
US11696955B2 (en) 2017-03-14 2023-07-11 Polyactiva Pty Ltd Drug-polymer conjugate
EP3600258A1 (en) 2017-03-20 2020-02-05 Teva Pharmaceuticals International GmbH Sustained release olanzapine formulaitons
US11116211B2 (en) 2018-03-09 2021-09-14 The University Of Akron Modification of segmented polyurethane properties by copolymerizing with pendant functionalized diols
EP3721857A1 (en) * 2019-04-11 2020-10-14 Dentsply DeTrey GmbH Dental composition
RU2737425C1 (ru) * 2020-02-17 2020-11-30 Елена Евгеньевна Масталыгина Мульчирующая биоразлагаемая полимерная пленка и способ ее получения (варианты)
WO2021220061A2 (en) 2020-05-01 2021-11-04 Ripple Therapeutics Corporation Heterodimer compositions and methods for the treatment of ocular disorders
US20240100012A1 (en) 2021-01-18 2024-03-28 Mark Hasleton Pharmaceutical dosage form
AU2022308198A1 (en) 2021-07-06 2024-02-01 Mark Hasleton Treatment of serotonin reuptake inhibitor withdrawal syndrome

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69708461T2 (de) * 1996-02-15 2002-06-27 Paul J Santerre Bioresponsive pharmakologisch aktive polymere und daraus hergestellte gegenstände
US20040091886A1 (en) * 2000-09-21 2004-05-13 Moore Jeffrey C. Method for generating recombinant polynucleotides
AR032052A1 (es) * 2000-12-29 2003-10-22 Artimplant Ab Polimero lineal de bloques, procedimiento para su preparacion, su uso, implantes, material para relleno, composiciones farmaceuticas y material polimerico poroso que comprenden dicho polimero lineal de bloques
CA2349989A1 (en) * 2001-06-07 2002-12-07 Paul J. Santerre Bioactive surface modifiers for polymers and articles made therefrom
AU2003267540A1 (en) * 2002-08-13 2004-02-25 Sirus Pharmaceuticals Ltd Biodegradable polymer
CA2467321A1 (en) * 2004-05-14 2005-11-14 Paul J. Santerre Polymeric coupling agents and pharmaceutically-active polymers made therefrom
WO2006024953A2 (en) * 2004-08-31 2006-03-09 Pharmacia & Upjohn Company Llc Glycerol branched polyethylene glycol human growth hormone conjugates, process for their preparation, and methods of use thereof
EP2010584A4 (en) * 2006-04-14 2010-07-21 Interface Biologics Inc GRAFT POLYMERS AND USES THEREOF
WO2008053362A2 (en) * 2006-06-30 2008-05-08 Interface Biologics, Inc. Bioresponsive polymers
KR101556248B1 (ko) * 2006-10-04 2015-09-30 노보 노르디스크 에이/에스 글리세롤이 연결된 페길화된 당 및 글리코펩티드
WO2009102795A1 (en) * 2008-02-15 2009-08-20 University Of Southern Mississippi Monomers and polymers with covalently-attached active ingredients

Also Published As

Publication number Publication date
IL212053A (en) 2015-11-30
SG195531A1 (en) 2013-12-30
EP2355853A4 (en) 2014-01-15
CA2949337A1 (en) 2010-04-15
CN102245214A (zh) 2011-11-16
IL229996A (en) 2016-06-30
JP5746629B2 (ja) 2015-07-08
WO2010040188A1 (en) 2010-04-15
CA2739078C (en) 2017-01-03
MY155629A (en) 2015-11-13
WO2010040188A9 (en) 2010-06-17
JP2012505161A (ja) 2012-03-01
ES2617913T3 (es) 2017-06-20
IL212053A0 (en) 2011-06-30
PT2355853T (pt) 2017-03-15
JP6290823B2 (ja) 2018-03-07
KR101726715B1 (ko) 2017-04-13
AU2009301646A1 (en) 2010-04-15
KR20110091854A (ko) 2011-08-16
IL229996A0 (en) 2014-01-30
SI2355853T1 (sl) 2017-04-26
CA2949337C (en) 2019-03-26
CA2739078A1 (en) 2010-04-15
EP2355853B1 (en) 2016-12-07
CN102245214B (zh) 2014-10-29
EP2355853A1 (en) 2011-08-17
AU2009301646B2 (en) 2013-09-05
JP2015180651A (ja) 2015-10-15
NZ603964A (en) 2014-12-24
HUE030895T2 (en) 2017-06-28
NZ592139A (en) 2013-03-28
ZA201102501B (en) 2011-11-30

Similar Documents

Publication Publication Date Title
DK2355853T3 (da) Bionedbrydelige polymer-bioaktivt fragmentkonjugater
WO2012139164A1 (en) Polymer conjugated prostaglandin analogues
EP2863921B1 (en) Polymer-nsaid conjugate
EP2340271A1 (en) Polymer-bioactive agent conjugates
US20180303948A1 (en) Polymer conjugate comprising a bioactive agent
AU2012258480B2 (en) Biodegradable polymer - bioactive moiety conjugates
US20120252967A1 (en) Polyurethanes
DK2340271T3 (da) Konjugater af polymer-bioaktivt middel