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US 2014/0271885 A1Published application
Copolymers for stable micelle formulations
AssigneeIntezyne Technologies, Inc.
InventorsKevin Sill, Tomas Vojkovsky
Life of this patent
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Abstract
The present invention relates to the field of polymer chemistry and more particularly to multiblock copolymers and micelles comprising the same. Compositions herein are useful for drug-delivery applications.
Claims2
A triblock copolymer of formula I:
- wherein:
- n is 20-500;
- x is 3 to 50;
- y is 5 to 100;
- Rx is a nitrolotriacetic acid, pyrazine-carboxylic acid, or hydroxypryridinone containing moiety;
- Ry is selected from one or more natural or unnatural amino acid side chain groups such that the overall block is hydrophobic;
- R1 is —Z(CH2CH2Y)p(CH2)tR3, wherein:
- Z is —O—, —NH—, —S—, —C≡C—, or —CH2—;
- each Y is independently —O— or —S—;
- p is 0-10;
- t is 0-10;
- and
- R3 is hydrogen, —N3, —CN, —NH2, —CH3,
- a strained cyclooctyne moiety, a mono-protected amine, a di-protected amine, an optionally protected aldehyde, an optionally protected hydroxyl, an optionally protected carboxylic acid, an optionally protected thiol, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety;
- Q is a valence bond or a bivalent, saturated or unsaturated, straight or branched C1-12 hydrocarbon chain, wherein 0-6 methylene units of Q are independently replaced by -Cy-, —O—, —NH—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —SO—, —SO2—, —NHSO2—, —SO2NH—, —NHC(O)—, —C(O)NH—, —OC(O)NH—, or —NHC(O)O—, wherein:
- -Cy- is an optionally substituted 5-8 membered bivalent, saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 8-10 membered bivalent saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
- R2 is a mono-protected amine, a di-protected amine, —N(R4)2, —NR4C(O)R4, —NR4C(O)N(R4)2, —NR4C(O)OR4, or —NR4SO2R4;
- and
- each R4 is independently hydrogen or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety, or:
- two R4 on the same nitrogen atom are taken together with said nitrogen atom to form an optionally substituted 4-7 membered saturated, partially unsaturated, or aryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
17 more elements
A drug loaded micelle comprising a triblock copolymer, wherein said micelle has a drug-loaded inner core, a crosslinked outer core, and a hydrophilic shell, wherein the triblock copolymer is of formula VI:
- wherein each of Q, J, T, x, y, n, Rx, Ry and R2 is as defined above and as described in classes and subclasses herein, both singly and in combination;
- M is a metal ion;
- Each RT independently selected from either -J-T or —Z(CH2CH2Y)p(CH2)tR3, wherein:
- Z is —O—, —S—, —C≡C—, or —CH2—;
- each Y is independently —O— or —S—;
- p is 0-10;
- t is 0-10;
- and
- R3 is —N3, —CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, a 9-30 membered crown ether, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety;
- Q is a valence bond or a bivalent, saturated or unsaturated, straight or branched C1-12 hydrocarbon chain, wherein 0-6 methylene units of Q are independently replaced by -Cy-, —O—, —NH—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —SO—, —SO2—, —NHSO2—, —SO2NH—, —NHC(O)—, —C(O)NH—, —OC(O)NH—, or —NHC(O)O—, wherein:
- -Cy- is an optionally substituted 5-8 membered bivalent, saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 8-10 membered bivalent saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
8 more elements
Dependencies are inferred from the claim text.