Amphiphilic star-like macromolecules for drug delivery
First Claim
Patent Images
1. A compound having formula (I):
-
R1—
((R2)a—
(R3)b—
(R4)c—
(R5)d—
(R6)e)n
(I)wherein R1 is a core comprising a polyol or polyacid;
each R2 independently is a divalent or polyvalent group having the formula —
X1—
R8—
(X1a)g—
, wherein X1 and X1a are independently —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent, and each R8 is independently —
(C1-8)alkylene-, branched —
(C1-8)alkylene- or —
(C6-10)aryl-;
a is 0 or an integer from 1 to about 10; and
g is an integer from 1 to about 6;
each R3 independently is a divalent dicarboxylic acid moiety having the formula —
C(═
O)—
R9—
C(═
O)—
, wherein R9 is an alkylene or cycloalkylene group containing from 1 to about 15 carbon atoms, substituted with a total of from 1 to about 10 hydroxy groups, wherein one or more of the hydroxy groups of the dicarboxylic acid are acylated with an acid residue; and
b is an integer from 1 to about 10;
each R4 independently is a divalent or polyvalent group having the formula —
X2—
R10—
(X2a)h—
, wherein X2 is —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent;
X2a is —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, or —
N(R7)— and
R10 is —
(C1-8)alkylene-, branched —
(C1-8)alkylene- or —
(C6-10)aryl-; and
c is 0 or an integer from 1 to about 10; and
h is an integer from 1 to 6;
each R5 independently is a group having the formula;
—
R12—
(R11)f—
R12—
X3—
wherein R11 is a sugar moiety;
or a poly(alkylene oxide) or poly(alkylene imine) group having the formula —
(—
X4—
R13)—
;
wherein R13 is —
(C2-40)alkylene- or branched —
(C3-40)alkylene-;
wherein each X3 is independently —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent; and
f is an integer from about 2 to about 150; and
d is from 1 to about 6;
each R12 is independently a bond, —
(C1-40)alkylene- or branched —
(C1-40)alkylene-groups, wherein each R12 is optionally substituted with one or more (e.g., 1, 2, or
3) functional groups; and
X4 is —
O—
, —
S—
, or —
N(R7)—
;
wherein n is from 2 to 12;
provided that a and b are not both zero;
wherein each R7 is independently selected from the group consisting of hydrogen, and C(1-40)alkyl group, where the alkyl group can be a straight-chain or branched group; and
Ra and Rb are each independently hydrogen (C1-8)alkyl, aryl, aryl(C1-8)alkylene; and
R6 is hydrogen, —
OH, —
ORa, —
NRaRb, —
CO2H, —
SO3H (sulfo), —
CH2—
OH, —
CH2—
ORa, —
CH2—
O—
CH2—
Ra, —
CH2—
NRaRb or a targeting moiety;
provided that at least one R6 group is a targeting moiety selected from —
CO2H, —
SO3H (sulfo), —
NH2, biotin, streptavidin, a sugar moiety, folic acid, an amino acid and a peptide; and
e is from 1 to about 6.
1 Assignment
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Accused Products
Abstract
The present invention provides polymeric compounds that can form micelles in solutions. These compounds have a hydrophobic, core that is coupled to a plurality of hydrophilic moieties.
24 Citations
58 Claims
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1. A compound having formula (I):
-
R1—
((R2)a—
(R3)b—
(R4)c—
(R5)d—
(R6)e)n
(I)wherein R1 is a core comprising a polyol or polyacid; each R2 independently is a divalent or polyvalent group having the formula —
X1—
R8—
(X1a)g—
, wherein X1 and X1a are independently —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent, and each R8 is independently —
(C1-8)alkylene-, branched —
(C1-8)alkylene- or —
(C6-10)aryl-;
a is 0 or an integer from 1 to about 10; and
g is an integer from 1 to about 6;each R3 independently is a divalent dicarboxylic acid moiety having the formula —
C(═
O)—
R9—
C(═
O)—
, wherein R9 is an alkylene or cycloalkylene group containing from 1 to about 15 carbon atoms, substituted with a total of from 1 to about 10 hydroxy groups, wherein one or more of the hydroxy groups of the dicarboxylic acid are acylated with an acid residue; and
b is an integer from 1 to about 10;each R4 independently is a divalent or polyvalent group having the formula —
X2—
R10—
(X2a)h—
, wherein X2 is —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent;
X2a is —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, or —
N(R7)— and
R10 is —
(C1-8)alkylene-, branched —
(C1-8)alkylene- or —
(C6-10)aryl-; and
c is 0 or an integer from 1 to about 10; and
h is an integer from 1 to 6;each R5 independently is a group having the formula;
—
R12—
(R11)f—
R12—
X3—wherein R11 is a sugar moiety;
or a poly(alkylene oxide) or poly(alkylene imine) group having the formula —
(—
X4—
R13)—
;
wherein R13 is —
(C2-40)alkylene- or branched —
(C3-40)alkylene-;
wherein each X3 is independently —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent; and
f is an integer from about 2 to about 150; and
d is from 1 to about 6;each R12 is independently a bond, —
(C1-40)alkylene- or branched —
(C1-40)alkylene-groups, wherein each R12 is optionally substituted with one or more (e.g., 1, 2, or
3) functional groups; and
X4 is —
O—
, —
S—
, or —
N(R7)—
;wherein n is from 2 to 12;
provided that a and b are not both zero;
wherein each R7 is independently selected from the group consisting of hydrogen, and C(1-40)alkyl group, where the alkyl group can be a straight-chain or branched group; and
Ra and Rb are each independently hydrogen (C1-8)alkyl, aryl, aryl(C1-8)alkylene; andR6 is hydrogen, —
OH, —
ORa, —
NRaRb, —
CO2H, —
SO3H (sulfo), —
CH2—
OH, —
CH2—
ORa, —
CH2—
O—
CH2—
Ra, —
CH2—
NRaRb or a targeting moiety;
provided that at least one R6 group is a targeting moiety selected from —
CO2H, —
SO3H (sulfo), —
NH2, biotin, streptavidin, a sugar moiety, folic acid, an amino acid and a peptide; and
e is from 1 to about 6. - View Dependent Claims (8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49)
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2. A compound having formula (I):
-
R1—
((R2)a—
(R3)b—
(R4)c—
(R5)d—
(R6)e)n
(I)wherein R1 is a core comprising a polyol or polyacid; each R2 independently is a divalent or polyvalent group having the formula —
X1—
R8—
(X1a)g—
, wherein X1 and X1a are independently —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent, and each R8 is independently —
(C1-8)alkylene-, branched —
(C1-8)alkylene- or —
(C6-10)aryl-;
a is an integer from 1 to about 10; and
g is an integer from 1 to about 6;each R3 independently is a divalent dicarboxylic acid moiety having the formula —
C(═
O)—
R9—
C(═
O)—
, wherein R9 is an alkylene or cycloalkylene group containing from 1 to about 15 carbon atoms, substituted with a total of from 1 to about 10 hydroxy groups, wherein one or more of the hydroxy groups of the dicarboxylic acid are acylated with an acid residue; and
b is an integer from 1 to about 10;each R4 independently is a divalent or polyvalent group having the formula —
X2—
R10—
(X2a)h—
, wherein X2 is —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent;
X2a is —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, or —
N(R7)— and
R10 is —
(C1-8)alkylene-, branched —
(C1-8)alkylene- or —
(C6-10)aryl-; and
c is 0 or an integer from 1 to about 10; and
h is an integer from 1 to 6;each R5 independently is a group having the formula;
—
R12—
(R11)f—
R12—
X3—wherein R11 is a sugar moiety;
or a poly(alkylene oxide) or poly(alkylene imine) group having the formula —
(—
X4—
R13)—
;
wherein R13 is —
(C2-40)alkylene- or branched —
(C3-40)alkylene-;
wherein each X3 is independently —
C(═
O)—
, —
C(═
S)—
, —
O—
, —
S—
, —
N(R7)—
or absent; and
f is an integer from about 2 to about 150; and
d is from 1 to about 6;each R12 is independently a bond, —
(C1-40)alkylene- or branched —
(C1-40)alkylene-groups, wherein each R12 is optionally substituted with one or more (e.g., 1, 2, or
3) functional groups; and
X4 is —
O—
, —
S—
, or —
N(R7)—
;wherein n is from 2 to 12;
provided that a and b are not both zero;
wherein each R7 is independently selected from the group consisting of hydrogen, and C(1-40)alkyl group, where the alkyl group can be a straight-chain or branched group; and
Ra and Rb are each independently hydrogen (C1-8)alkyl, aryl, aryl(C1-8)alkylene; andR6 is hydrogen, —
OH, —
ORa, —
NRaRb, —
CO2H, —
SO3H (sulfo), —
CH2—
OH, —
CH2—
ORa, —
CH2—
O—
CH2—
Ra, —
CH2—
NRaRb or a targeting moiety; and
e is from 1 to about 6. - View Dependent Claims (4, 5, 6, 7, 19, 20, 34, 50, 51, 52, 53, 54, 55, 56, 57, 58)
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3. A compound having the formula
Specification