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    • 50. 发明申请
    • MODIFIED POLY(PROPYLENE-IMINE) DENDRIMERS AND THEIR USE AS TRANSFECTION AGENTS FOR ANIONIC BIOACTIVE FACTORS
    • 改性聚(丙烯 - 胺)降解剂及其作为阳离子生物活性因子转移剂的用途
    • WO2007006700A1
    • 2007-01-18
    • PCT/EP2006/063888
    • 2006-07-05
    • JANSSEN PHARMACEUTICA N.V.TACK, FrederikJANSSEN, Henricus, MarieMEIJER, Egbert, WillemJANICOT, Michel, Marie, FrançoisBREWSTER, Marcus, Eli
    • TACK, FrederikJANSSEN, Henricus, MarieMEIJER, Egbert, WillemJANICOT, Michel, Marie, FrançoisBREWSTER, Marcus, Eli
    • C07C235/50C07C235/10C07C233/36A61P35/00A61K31/166A61K31/16
    • C07C233/36C07C235/10C07C235/50C08G83/004
    • The present invention is concerned with modified poly-(propylene imine) dendrimers, comprising cationic internal ammonium groups and external non-toxic endgroups, pharmaceutical compositions comprising said dendrimers, methods for the production of said dendrimers and their use as transfections agents for anionic bioactive therapeutic factors, for use in gene therapy, in particular for the treatment of cancer. The modified poly-(propylene imine) dendrimer of generation 1, 2, 3, 4 or 5, also comprising incomplete dendrimers and mixtures thereof, comprising external end groups and internal amine functions are characterized in that: (a) substantially all external endgroups are groups of formula (I) wherein R is a radical selected from the group of C 1-10 alkyl, polyethylene glycol radical and polyethylene glycol gallyl radical ; and (b) substantially all internal amine functions are quaternary cationic ammonium functions. Most preferred are the quaternized compounds DAB-dendr-(NHCOCH 3 ) 4 , DAB-dendr-(NHCOCH 3 ) 8 , DAB-dendr-(NHCOCH 3 ) 16 , DAB-dendr-(NHCOCH 3 ) 32 , DAB-dendr-(NHCOCH 3 ) 64 , DAB-dendr-(NHCOPh((EO) 4 OMe) 3 ) 4 , DAB-dendr-(NHCOPh((EO) 4 OMe) 3 ) 8 , DAB-dendr-(NHCOPh((EO) 4 OMe) 3 ) 16 , DAB-dendr-(NHCOPh((EO) 4 OMe) 3 ) 32 and DAB-dendr-(NHCOPh((EO) 4 OMe) 3 ) 64 .
    • 本发明涉及包含阳离子内铵基团和外部无毒端基的改性聚(亚丙基亚胺)树枝状聚合物,包含所述树枝状聚合物的药物组合物,用于生产所述树枝状大分子的方法及其作为阴离子生物活性治疗用转染剂的用途 因素,用于基因治疗,特别是用于治疗癌症。 还包含不完全树枝状大分子及其混合物的包含外部末端基团和内部胺官能团的1,2,3,4或5代的改性聚(亚丙基亚胺)树枝状聚合物的特征在于:(a)基本上所有的外部末端基团 式(I)的基团,其中R是选自C 1-10烷基,聚乙二醇基和聚乙二醇gallyl基的基团; 和(b)基本上所有的内部胺官能团都是季铵阳离子铵官能团。 最优选的是季铵化合物DAB-树枝状(NHCOCH 3)4,DAB-树枝状(NHCOCH 3)8, DAB-dendr-(NHCOCH 3 3)16,DAB-树枝状(NHCOCH 3 3)32 ,DAB-树枝状(NHCOCH 3 N)64,DAB-树枝状(NHCOPh((EO)4 OMe)3 DAB-树枝状 - (NHCOPh((EO)4 OMe)3 3 >,DAB-树枝状(NHCOPh((EO)4 OMe)3)16,DAB-树枝状(NHCOPh((EO) 32 N,N 3 O 3)和DAB-树枝状(NHCOPh((EO)4 OMe)) 64>