DK2644192T3 - Cancercelle-targeting under anvendelse af nanopartikler - Google Patents

Cancercelle-targeting under anvendelse af nanopartikler Download PDF

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Publication number
DK2644192T3
DK2644192T3 DK13162786.1T DK13162786T DK2644192T3 DK 2644192 T3 DK2644192 T3 DK 2644192T3 DK 13162786 T DK13162786 T DK 13162786T DK 2644192 T3 DK2644192 T3 DK 2644192T3
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polymer
gene
nanoparticle
polymers
ligand
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DK13162786.1T
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English (en)
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Mir Mukkaram Ali
Stephen E Zale
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Pfizer
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Claims (12)

1. Fremgangsmåde til fremstilling afen stealth-nanopartikel, omfattende: at tilvejebringe et terapeutisk middel; at tilvejebringe en første polymer; at tilvejebringe en PSMA-ligand med en molekylvægt på under 2000 g/mol; at reagere den første polymer med PSMA-liganden for at fremstille en ligandbundet polymer; og at blande den ligand-bundne polymer med en anden, ikke-funktionaliseret polymer, og det terapeutiske middel; således at stealth-nanopartiklen dannes.
2. Fremgangsmåde ifølge krav 1, hvor PSMA-liganden har formlen I, II, III eller IV:
I II III IV !) og enantiomerer, stereoisomerer, rotamerer, tautomerer, diastereomerer eller racemater deraf; hvor m og n hver især uafhængigt er 0, 1,2 eller 3; p er 0 eller 1; R1, R2, R4 og R5 hver især uafhængigt er udvalgt fra gruppen bestående af substitueret eller usubstitueret alkyl, substitueret eller usubstitueret aryl og en hvilken som helst kombination deraf; og R3 er H eller Ci_6-alkyl, og hvor R1, R2, R3 og R5 omfatter et fastgørelsespunkt til nanopartiklen.
3. Fremgangsmåde ifølge krav 2, hvor R1, R2, R4 og R5 hver især uafhængigt er Ci_6-alkyl eller phenyl, eller en hvilken som helst kombination af Ci_6-alkyl eller phenyl, hvilke er uafhængigt substitueret en eller flere gange med OH, SH, NH2 eller C02H, og hvor alkylgruppen kan være afbrudt af N(H), S eller O.
4. Fremgangsmåde ifølge krav 2, hvor PSMA-liganden har formen I, eller en enantiomer, stereoisomer, rotamer, tautomer, diastereomerer eller racemat deraf; hvor R1 er C-i-6-alkyl eller phenyl, eller en hvilken som helst kombination af Ci-6-alkyl eller phenyl, hvilke uafhængigt er substitueret en eller flere gange med OH, SH, NH2 eller CO2H, og hvor alkylgruppen kan være afbrudt af N(H), S eller O.
5. Fremgangsmåde ifølge krav 4, hvor PSMA-liganden er
og enantiomerer, stereoisomerer, rotamerer, tautomerer, diastereomerer eller racemater deraf, hvor n er 1, 2, 3, 4, 5 eller 6, og hvor NH2-gruppen tjener som punktet for kovalent binding til nanopartiklen.
6. Fremgangsmåde ifølge krav 4, hvor PSMA-liganden er
or
og enantiomerer, stereoisomerer, rotamerer, tautomerer, diastereomerer eller racemater deraf, og hvor NH2-gruppen tjener som punktet for kovalent binding til nanopartiklen.
7. Fremgangsmåde ifølge et af de foregående krav, hvor den første polymer omfatter en copolymer på to eller flere polymerer.
8. Fremgangsmåde ifølge et af de foregående krav, hvor den anden, ikke-funktionaliserede polymer omfatter en copolymer på to eller flere polymerer.
9. Fremgangsmåde ifølge krav 7 eller 8, hvor copolymeren er en copolymer af PLA og PEG eller PLGA og PEG.
10. Fremgangsmåde ifølge krav 9, hvor den ligand-bundne polymer er kovalent bundet til PSMA-liganden via en carboxylgruppe eller en funktionel ma-leimidgruppe ved den frie ende af PEG.
11. Fremgangsmåde ifølge et af de foregående krav, hvor det terapeutiske middel er udvalgt fra gruppen bestående af kemoterapeutiske midler, såsom doxorubicin, gemcitabin, daunorubicin, procarbazin, mitomycin, cytarabin, etoposid, methotrexat, 5-fluoruracil, vinblastin, vineristin, bleomycin, pacli-taxel, docetaxel, aldesleukin, asparaginase, busulfan, carboplatin, cladribin, camptothecin, CPT-11, 10-hydroxy-7-ethylcamptothecin, daearbazin, S-l ca-pecitabin, ftorafur, 5'deoxyfluororidin, UFT, eniluracil, deoxycytidin, 5-aza-cytosin, 5-azadeoxycytosin, allopurinol, 2-chloradenosin, trimetrexat, aminop-terin, methylen- 10-deazaaminopterin, oxaplatin, picoplatin, tetraplatin, satraplatin, platinum-DACH, ormaplatin, CI-973, JM-216 og analoger deraf, epiru-bicin, etoposidphosphat, 9-aminocamptothecin, 10,11-methylendioxycampto-thecin, karenitecin, 9-nitrocamptothecin, TAS 103, vindesin, L-phenylalanin-sennep, ifosphamidmefosphamid, perfosfamid, trophosphamidearmustin, semustin, epothiloner A-E, tomudex, 6-mercaptopurin, 6-thioguanin, amsa-crin, etoposidphosphat, karenitecin, acyclovir, valacyclovir, ganciclovir, amantadin, rimantadin, lamivudin, zidovudin, bevacizumab, trastuzumab, rituximab og 5-fluorouracil og kombinationer deraf, eller en siRNA.
12. Fremgangsmåde ifølge et af kravene 1 til 10, hvor det terapeutiske middel er mitoxantron eller docetaxel.
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