SI2285350T1 - Postopki za pripravo diblok kopolimerov, funkcionaliziranih s sredstvom za ciljanje, za uporabo pri izdelavi terapevtskih nanodelcev - Google Patents

Postopki za pripravo diblok kopolimerov, funkcionaliziranih s sredstvom za ciljanje, za uporabo pri izdelavi terapevtskih nanodelcev Download PDF

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SI2285350T1
SI2285350T1 SI200931767T SI200931767T SI2285350T1 SI 2285350 T1 SI2285350 T1 SI 2285350T1 SI 200931767 T SI200931767 T SI 200931767T SI 200931767 T SI200931767 T SI 200931767T SI 2285350 T1 SI2285350 T1 SI 2285350T1
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polymer
targeting agent
units
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Mir M. Ali
Jeff Hrkach
Stephen E. Zale
De Cienfuegos Luis Alvarez
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Pfizer Inc.
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    • 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
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    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
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Claims (16)

  1. Postopki za pripravo diblok kopolimerov, funkcionaliziranih s sredstvom za ciljanje, za uporabo pri izdelavi terapevtskih nanodelcev Patentni zahtevki
    1. Postopek za pripravo nanodelca, ki obsega: zagotavljanje sredstva za ciljanje (TA); zaščitenje funkcionalnih skupin sredstva za ciljanje; zagotavljanje funkcionaliziranega polietilen glikol) (PEG) polimera; reagiranje funkcionaliziranega polietilen glikol) polimera z zaščitenim sredstvom za ciljanje (PRO-TA), da se tvori kompleks sredstva za ciljanje in PEG-polimera; konjugiranje kompleksa sredstva za ciljanje in PEG-polimera z drugim polimerom, da se tvori kompleks sredstva za ciljanje in PEG-polimera ter drugega polimera; in mešanje kompleksa sredstva za ciljanje in PEG-polimera ter drugega polimera z drugim polimerom in terapevtskim sredstvom, da se tvori nanodelec.
  2. 2. Postopek po zahtevku 1, pri čemer je poli(etilen glikol) hetero-bifunkcionalen in sredstvo za ciljanje je kovalentno vezano na α-konec polietilen glikola) in vsaj ena funkcionalna skupina, ki sproži polimerizacijo, je prisotna na ω-koncu polietilen glikola).
  3. 3. Postopek po zahtevku 2, pri čemer je vsaj ena funkcionalna skupina, ki sproži polimerizacijo, hidroksilna (-OH) skupina ali aminska (-NH2) skupina na prostem ω-koncu, ki reagira z drugim kopolimerom.
  4. 4. Postopek po zahtevku 3, pri čemer drugi polimer obsega mešanico dveh ali več polimerov in vsebuje vsaj eno funkcionalno skupino, ki reagira s funkcionalno skupino, ki je prisotna na prostem ω-koncu poli(etilen glikola) in vsaj ena funkcionalna skupina mešanice dveh ali več polimerov je hidroksilna skupina, NHS-skupina ali aminska skupina.
  5. 5. Postopek po zahtevku 1, pri čemer je drugi polimer ali kopolimer poliestrski kopolimer, ki vsebuje vsaj eno funkcionalno skupino, izbrano izmed hidroksilne skupine, NHS- skupine ali aminske skupine in ki reagira s funkcionalno skupino, ki je prisotna na prostem ω-koncu poli(etilen glikola).
  6. 6. Postopek po zahtevku 4, pri čemer je drugi polimer ali kopolimer poliestrski kopolimer, ki vsebuje vsaj eno funkcionalno skupino, izbrano izmed hidroksilne skupine, NHS-skupine ali aminske skupine in ki reagira s funkcionalno skupino, kije prisotna na prostem ω-koncu poli(etilen glikola).
  7. 7. Postopek po zahtevku 6, pri čemer poliestrski kopolimer obsega heteropolimer ali homopolimer.
  8. 8. Postopek po zahtevku 7, pri čemer heteropolimer obsega enote mlečne kisline in glikolne kisline ali poli(mlečne kisline-ko-glikolne kisline) in enote poli(laktid-ko-glikolida) (PLGA); in homopolimer obsega enote glikolne kisline (PGA), enote mlečne kisline (PLA), enote poli-L-mlečne kisline, enote poli-D-mlečne kisline, enote poli-D,L-mlečne kisline, enote poli-L-laktida, enote poli-D-laktida ali enote poli-D,L-laktida.
  9. 9. Postopek po zahtevku 6, pri čemer je poliestrski kopolimer izbran izmed polihidroksikislin; PEGiliranih polimerov in kopolimerov laktidnih enot in glikolidnih enot, PEGiliranega PLA, PEGiliranega PGA, PEGiliranega PLGA, polianhidridov, poli(orto estra) PEGiliranega poli(orto estra), poli(kaprolaktona), PEGiliranega poli(kaprolaktona), polilizina, PEGiliranega polilizina, polietilen inlina), PEGiliranega poli(etilen imina), poli(L-laktid-ko-L-lizina), poli(serin estra), poli(4-hidroksi-L-prolin estra), poli[a-(4-aminobutil)-L-glikolne kisline] ali derivatov le-teh.
  10. 10. Postopek po zahtevku 1, pri čemer je funkcionalna skupina na sredstvu za ciljanje prosta skupina karboksilne kisline ali prosta hidroksilna kislina in prosta skupina karboksilne kisline ali prosta hidroksilna skupina je zaščitena pred reagiranjem funkcionaliziranega poli(etilen glikol) polimera s sredstvom za ciljanje, da se tvori kompleks sredstva za ciljanje in PEG-polimera.
  11. 11. Postopek po zahtevku 4, pri čemer je funkcionalna skupina drugega polimera: a) aminska skupina, ki reagira s hidroksilno skupino ali skupino karboksilne kisline na kompleksu sredstva za ciljanje in PEG; ali b) hidroksilna skupina ali NHS-skupina, ki reagira z aminsko skupino na kompleksu sredstva za ciljanje in PEG.
  12. 12. Postopek po zahtevku 6, pri čemer je funkcionalna skupina drugega polimera ali kopolimera: a) aminska skupina, ki reagira s hidroksilno skupino ali skupino karboksilne kisline na kompleksu sredstva za ciljanje in PEG; ali b) NHS-skupina ali hidroksilna skupina, ki reagira z aminsko skupino na kompleksu sredstva za ciljanje in PEG.
  13. 13. Postopek po zahtevku 1, pri čemer je drugi polimer mešanica vsaj dveh polimerov, ki sta lahko enaka ali različna polimera, pri čemer prvi od vsaj dveh polimerov vsebuje vsaj eno hidroksilno skupino ali NHS-skupino kot funkcionalno skupino in drugi od vsaj dveh polimerov vsebuje vsaj eno aminsko skupino kot funkcionalno skupino.
  14. 14. Postopek po zahtevku 1, pri čemer je terapevtsko sredstvo antibiotik, sredstvo proti raku, protivirusno sredstvo, protivnetno sredstvo ali diagnostično sredstvo, antigen cepiva ali nutracevtik.
  15. 15. Postopek po zahtevku 1, pri čemer je vsaj eno sredstvo za ciljanje izbrano izmed protiteles, ligandov prostatnega specifičnega membranskega antigena (PMSA) in polipeptidov, ki se vežejo na receptor epidermalnega rastnega faktoija (EGFR), somatostatinskega receptorja (SSTR), receptorja inzulinu podobnega rastnega faktorja, receptorja folne kisline, receptorja HER2, receptorja interlevkina-13, receptorja gastrin sproščujočega peptida, CD30, receptorja vazoaktivnega intestinalnega peptida, gastrinskega receptorja, prostatnega specifičnega antigena in/ali estrogenskega receptoija.
  16. 16. Postopek po zahtevku 1, pri čemer se postopek opravi v vodnem mediju ali v organskem topilu.
SI200931767T 2008-06-16 2009-06-16 Postopki za pripravo diblok kopolimerov, funkcionaliziranih s sredstvom za ciljanje, za uporabo pri izdelavi terapevtskih nanodelcev SI2285350T1 (sl)

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US6171208P 2008-06-16 2008-06-16
PCT/US2009/047554 WO2010005740A2 (en) 2008-06-16 2009-06-16 Methods for the preparation of targeting agent functionalized diblock copolymers for use in fabrication of therapeutic targeted nanoparticles
EP09794932.5A EP2285350B1 (en) 2008-06-16 2009-06-16 Methods for the preparation of targeting agent functionalized diblock copolymers for use in fabrication of therapeutic nanoparticles

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