Cationic graft-copolymer for non-viral gene delivery vector
OwnerYasuhiko Onishiinventor
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Abstract
A cationic graft-copolymer for a non-viral gene delivery vector comprising a unit derived from a cationic derivative of a water-soluble linear polymers having a hydroxyl groups, namely, a cationic polysaccharide of the following formula (1) and the cationic derivative of polyvinylalcohol of the following formula (2) or the cationic derivative of the partial hydrolyzed polyvinylalcohol of the following formula (3) and a unit derived from a polymerizable olefin compound of the following formula (4) a process for preparing the same and a transfection reagent made therefrom.
Claims3
A non-viral gene delivery vector formed from an aqueous solution of a cationic graft-copolymer of a water-soluble linear backbone polymer having hydroxyl groups, for a non-viral gene delivery vector, comprising a unit derived from a cationic water-soluble linear polysaccharide of the following formula (1)
- [C6H7O2(OH)3-a(OX)a]xH2O (1)
- or a unit derived from a water-soluble linear polyvinylalcohol of the following formula (2) or a partial hydrolyzed alcohol of the following formula (3)
- —[CH2CH(OH)1-b(OX)b]n— (2)
- —[CH2CH(OH)1-b-c(OX)b(OAc)c]n— (3),
- wherein X is a —(CH2)mR1 organic radical where R1 is a member of the class consisting of:
- —NH2 radical,
- —N(CH3)2 radical,
- —N(C2H5)2 radical,
- —N+(C2H5)3 radical,
- —N+(CH2)2CH2CH(OH)CH3 radical,
- —N+(C2H5)2CH2CH(OH)CH3 radical,
- —N+(C2H5)2(C2H5)N(C2H5)2 radical,
- —C6H4NH2 radical,
- —COC6H4NH2 radical,
- —COR2 radical where R2 is —CH2NH2 or —C6H4NH2, and
- —CH2CH(OH)CH2R3 radical where R3 is —NH2, —N(CH3)2, —N(C2H5)2, or —N+(C2H5)3 radical,
- where m is a natural number of 1 to 3, a is a positive number having a value of 0<a<3, b is a positive number having a value of 0<b<1, x and n are natural numbers having a value of 5 or more, 1>b+c, and Ac is acetyl radical;
- and
- a unit derived from a polymerize-able olefin compound of the following formula (4):
- wherein R4, R5 and R6 are each selected from the group consisting of hydrogen and CH3, and R7 is a member of the group consisting of:
- where R8 is a member of the class consisting of:
- hydrogen, C1-C12 alkyl radicals, cyclohexyl radical, C1-C4 hydroxyalkyl radicals, C1-C8 aminoalkyl radicals, C1-C8 dialkylaminoalkyl radicals, glycidyl radical, tetrahydrofuran radical, C1-C4 lower alkyl-substituted tetrahydrofuran radical, benzyl radical, a (CH2CH2O)yCH2CH2OH radical where y is a positive integer from 1 to 10, and —N(R9)2, where the two R9's which may be the same or different, are either hydrogen or a C1-C4 alkyl radical;
- wherein R10 is a C1-C8 alkyl radical, phenyl radical, tolyl radical, pyridine radical, pyrrolidone radical;
- and
- where R11 is NH2, NHCH3, N,N-dimethylamino radical, N,N-dimethylaminopropylamino radical, and morpholine radical.
A process for preparing a non-viral gene delivery vector formed from an aqueous solution of a cationic graft-copolymer of a water-soluble linear backbone polymer having hydroxyl groups, for a non-viral gene delivery vector, which comprises reacting a cationic water-soluble linear polysaccharide of the following formula (1)
- [C6H7O2(OH)3-a(OX)a]xH2O (1)
- or a unit derived from a water-soluble linear polyvinylalcohol of the following formula (2) or a partial hydrolyzed alcohol of the following formula (3)
- —[CH2CH(OH)1-b(OX)b]n— (2)
- —[CH2CH(OH)1-b-c(OX)b(OAc)c]n— (3),
- wherein X is a —(CH2)mR1 organic radical where R1 is a member of the class consisting of:
- —NH2 radical,
- —N(CH3)2 radical,
- —N(C2H5)2 radical,
- —N+(C2H5)3 radical,
- —N+(CH2)2CH2CH(OH)CH3 radical,
- —N+(C2H5)2CH2CH(OH)CH3 radical,
- —N+(C2H5)2(C2H5)N(C2H5)2 radical,
- —C6H4NH2 radical,
- —COC6H4NH2 radical,
- —COR2 radical where R2 is —CH2NH2 or —C6H4NH2, and
- —CH2CH(OH)CH2R3 radical where R3 is —NH2, —N(CH3)2, —N(C2H5)2, or —N+(C2H5)3 radical,
- where m is a natural number of 1 to 3, a is a positive number having a value of 0<a<3, b is a positive number having a value of 0<b<1, x and n are natural numbers having a value of 5 or more, 1>b+c, and Ac is acetyl radical;
- with a polymerize-able olefin compound of the formula (4′):
- wherein R4, R5 and R6 are each selected from the group consisting of hydrogen and CH3, and R7 is a member of the group consisting of:
- where R8 is a member of the class consisting of hydrogen, C1-C12 alkyl radicals, cyclohexyl radical, C1-C4 hydroxyalkyl radicals, C1-C8 aminoalkyl radicals, C1-C8 dialkylaminoalkyl radicals, glycidyl radical, tetrahydrofuran radical, C1-C4 lower alkyl-substituted tetrahydrofuran radical, benzyl radical, a (CH2CH2O)yCH2CH2OH radical where y is a positive integer from 1 to 10, and —N(R9)2 where the two R9's which may be the same or different, are either hydrogen or a C1-C4 alkyl radical;
- where R10 is a C1-C8 alkyl radical, phenyl radical, tolyl radical, pyridine radical, pyrrolidone radical;
- and
- where R11 is NH2, NHCH3, N,N-dimethylamino radical, N,N-dimethylaminopropylamino radical, and morpholine radical.
3-6. (canceled)
Dependencies are inferred from the claim text.