TY - PAT
T1 - Modified poly(propylene-imine) dendrimers and their use as transfection agents for anionic bioactive factors
AU - Tack, F.
AU - Janssen, H.Marie
AU - Meijer, E.W.
AU - Janicot, M.M.F.
AU - Brewster, M.Eli
PY - 2007/1/18
Y1 - 2007/1/18
N2 - The present invention is concerned with modified poly(propylene imine) dendrimers, comprising cationic internal ammonium groups and external non-toxic endgroups, pharmaceutical compns. comprising the dendrimers, methods for the prodn. of the 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 mixts. thereof, comprising external end groups and internal amine functions are characterized in that: (a) substantially all external end groups are groups of -NHCOR, wherein R is a radical selected from the group of C1-10alkyl, 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 compds. DAB-dendr-(NHCOCH3)4, DAB-dendr-(NHCOCH3)8, DAB-dendr-(NHCOCH3)16, DAB-dendr-(NHCOCH3)32, DAB-dendr-(NHCOCH3)64, DAB-dendr-(NHCOPh((EO)4OMe)3)4, DAB-dendr-(NHCOPh((EO)4OMe)3)8, DAB-dendr-(NHCOPh((EO)4OMe)3 )16, DAB-dendr-(NHCOPh((EO)4OMe)3 )32 and DAB-dendr-(NHCOPh((EO)4OMe)3 )64.
AB - The present invention is concerned with modified poly(propylene imine) dendrimers, comprising cationic internal ammonium groups and external non-toxic endgroups, pharmaceutical compns. comprising the dendrimers, methods for the prodn. of the 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 mixts. thereof, comprising external end groups and internal amine functions are characterized in that: (a) substantially all external end groups are groups of -NHCOR, wherein R is a radical selected from the group of C1-10alkyl, 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 compds. DAB-dendr-(NHCOCH3)4, DAB-dendr-(NHCOCH3)8, DAB-dendr-(NHCOCH3)16, DAB-dendr-(NHCOCH3)32, DAB-dendr-(NHCOCH3)64, DAB-dendr-(NHCOPh((EO)4OMe)3)4, DAB-dendr-(NHCOPh((EO)4OMe)3)8, DAB-dendr-(NHCOPh((EO)4OMe)3 )16, DAB-dendr-(NHCOPh((EO)4OMe)3 )32 and DAB-dendr-(NHCOPh((EO)4OMe)3 )64.
M3 - Patent publication
ER -
