Block copolymers for stable micelles
AssigneeIntezyne Technologies, Inc.
InventorsKevin Sill, Tomas Vojkovsky, Adam Carie
Life of this patent
Estimating the term…
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.
Claims14
A 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 VII:
- wherein:
- n is 20-500;
- m is 1 or 2;
- x1 is 1-20;
- x2 is 0-20;
- y is 5 to 100;
- Ry is selected from one or more natural or unnatural amino acid side chain groups such that the overall block is hydrophobic;
- M is a metal ion;
- RT is —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;
- each R3 is independently selected from —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;
- and
- the drug is SN-38.
A 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 VII:
- wherein:
- n is 20-500;
- m is 1 or 2;
- x1 is 1-20;
- x2 is 0-20;
- y is 5 to 100;
- Ry is selected from one or more natural or unnatural amino acid side chain groups such that the overall block is hydrophobic;
- M is a metal ion;
- RT is —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;
- each R3 is independently selected from —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;
- and
- the drug is aminopterin.
A 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 VII:
- wherein:
- n is 20-500;
- m is 1 or 2;
- x1 is 1-20;
- x2 is 0-20;
- y is 5 to 100;
- Ry is selected from one or more natural or unnatural amino acid side chain groups such that the overall block is hydrophobic;
- M is a metal ion;
- RT is —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;
- each R3 is independently selected from —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;
- and
- the drug is epothilone D.
A 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 VII:
- wherein:
- n is 20-500;
- m is 1 or 2;
- x1 is 1-20;
- x2 is 0-20;
- y is 5 to 100;
- Ry is selected from one or more natural or unnatural amino acid side chain groups such that the overall block is hydrophobic;
- M is a metal ion;
- RT is —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;
- each R3 is independently selected from —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;
- and
- the drug is daunorubicin.
A 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 VII:
- wherein:
- n is 20-500;
- m is 1 or 2;
- x1 is 1-20;
- x2 is 0-20;
- y is 5 to 100;
- Ry is selected from one or more natural or unnatural amino acid side chain groups such that the overall block is hydrophobic;
- M is a metal ion;
- RT is —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;
- each R3 is independently selected from —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;
- and
- the drug is berberine.
A 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 VII:
- wherein:
- n is 20-500;
- m is 1 or 2;
- x1 is 1-20;
- x2 is 0-20;
- y is 5 to 100;
- Ry is selected from one or more natural or unnatural amino acid side chain groups such that the overall block is hydrophobic;
- M is a metal ion;
- RT is —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;
- each R3 is independently selected from —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;
- and
- the drug is cabazitaxel.
A 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 VII:
- wherein:
- n is 20-500;
- m is 1 or 2;
- x1 is 1-20;
- x2 is 0-20;
- y is 5 to 100;
- Ry is selected from one or more natural or unnatural amino acid side chain groups such that the overall block is hydrophobic;
- M is a metal ion;
- RT is —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;
- each R3 is independently selected from —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;
- and
- the drug is docetaxel.
Dependencies are inferred from the claim text.