초록 ▼

Block copolymers based on poly(ortho esters) containing amine groups. These block copolymers have both hydrophilic and hydrophobic blocks. They form micelles in aqueous solution, making them suitable for encapsulation or solubilization of hydrophobic or water-insoluble materials; and they also form

Block copolymers based on poly(ortho esters) containing amine groups. These block copolymers have both hydrophilic and hydrophobic blocks. They form micelles in aqueous solution, making them suitable for encapsulation or solubilization of hydrophobic or water-insoluble materials; and they also form bioerodible matrices for the sustained release of active agents.

대표청구항 ▼

1. A micellar pharmaceutical composition for the delivery of a hydrophobic or water-insoluble active agent, comprising the active agent physically entrapped within but not covalently bonded to a drug carrier comprising a block copolymer of formula X, formula Y, or formula Z:RA?[OCH2CH2]f-[POE]g-H??(

1. A micellar pharmaceutical composition for the delivery of a hydrophobic or water-insoluble active agent, comprising the active agent physically entrapped within but not covalently bonded to a drug carrier comprising a block copolymer of formula X, formula Y, or formula Z:RA?[OCH2CH2]f-[POE]g-H??(X), RA?[OCH2CH2]f-[POE]g-[OCH2CH2]h?ORB??(Y), H?A-[POE]g-[OCH2CH2]h-[POE]j-H??(Z), where:RA is C1-C4 alkyl; RB is C1-C4 alkyl; f and h are independently an integer from 2 to 1000; g and j are independently an integer from 2 to 200; POE is a poly(ortho ester) unit of formula IA or formula IIA: whereR* is a C1-C4 alkyl; R is a bond, ?(CH2)?, or ?(CH2)b?O?(CH2)c?; where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5; and each A is independently selected from R1, R2, R3, and R4, where R1 is: where:p is an integer of 1 to 20; R5 is hydrogen or C1-C4 alkyl; and R6 is: where:s is an integer of 0 to 30; t is an integer of 2 to 200; and R7 is hydrogen or C1-C4 alkyl; R2 is: R3 is: where:x is an integer of 0 to 30; y is an integer of 2 to 200; R8 is hydrogen or C1-C4 alkyl; R9 and R10 are independently C1-C12 alkylene; R11 is hydrogen or C1-C6 alkyl and R12 is C1-C6 alkyl; or R11 and R12 together are C3-C10 alkylene; and R4 is the residue of a diol containing at least one amine functionality incorporated therein; in which at least 0.1 mol % of the A units are R1, and at least 0.1 mol % of the A units are R4. 2. The pharmaceutical composition of claim 1 where the fraction of the active agent is from 1% to 60% by weight of the composition.3. The pharmaceutical composition of claim 2 where the fraction of the active agent is from 5% to 30% by weight of the composition.4. The pharmaceutical composition of claim 1 where the active agent is selected from anti-infectives, antiseptics, steroids, therapeutic polypeptides, anti-inflammatory agents, cancer chemotherapeutic agents, narcotics, local anesthetics, antiangiogenic agents, vaccines, antigens, DNA, and antisense oligonucleotides.5. The pharmaceutical composition of claim 1 where the active agent is a cancer chemotherapeutic agent.6. The pharmaceutical composition of claim 1 where the active agent is an anti-inflammatory agent.7. A method of treating a disease state treatable by controlled release local administration of an active agent, comprising locally administering a therapeutically effective amount of the active agent in the form of a pharmaceutical composition of claim 1.8. A composition for the sustained release of an active agent, comprising the active agent dispersed in a matrix comprising a block copolymer of formula X, formula Y, or formula Z:RA?[OCH2CH2]f-[POE]g-H??(X), RA?[OCH2CH2]f-[POE]g-[OCH2CH2]h?ORB??(Y), H?A-[POE]g-[OCH2CH2]h-[POE]j-H??(Z), where:RA is C1-C4 alkyl; RB is C1-C4 alkyl; f and h are independently an integer from 2 to 1000; g and j are independently an integer from 2 to 200; POE is a poly(ortho ester) unit of formula IA or formula IIA: whereR* is a C1-C4 alkyl; R is a bond, ?(CH2)?, or ?(CH2)b?O?(CH2)c?; where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5; and each A is independently selected from R1, R2, R3, and R4, where R1 is: where:p is an integer of 1 to 20; R5 is hydrogen or C1-C4 alkyl; and R6 is: where:s is an integer of 0 to 30; t is an integer of 2 to 200; and R7 is hydrogen or C1-C4 alkyl; R2 is: R3 is: where:x is an integer of 0 to 30; y is an integer of 2 to 200; R8 is hydrogen or C1-C4 alkyl; R9 and R10 are independently C1-C12 alkylene; R11 is hydrogen or C1-C6 alkyl and R12 is C1-C6 alkyl; or R11 and R12 together are C3-C10 alkylene; and R4 is the residue of a diol containing at least one amine functionality incorporated therein; in which at least 0.1 mol % of the A units are R1, and at least 0.1 mol % of the A units are R4. 9. The pharmaceutical composition of claim 8 where the fraction of the active agent is from 1% to 60% by weight of the composition.10. The pharmaceutical composition of claim 9 where the fraction of the active agent is from 5% to 30% by weight of the composition.11. The pharmaceutical composition of claim 8 where the active agent is selected from anti-infectives, antiseptics, steroids, therapeutic polypeptides, anti-inflammatory agents, cancer chemotherapeutic agents, narcotics, local anesthetics, antiangiogenic agents, vaccines, antigens, DNA, and antisense oligonucleotides.12. The pharmaceutical composition of claim 8 where the active agent is a local anesthetic.13. The pharmaceutical composition of claim 12 further comprising a glucocorticosteroid.14. A method of treating a disease state treatable by controlled release local administration of an active agent, comprising locally administering a therapeutically effective amount of the active agent in the form of a pharmaceutical composition of claim 8.15. A method of preventing or relieving local pain at a site in a mammal, comprising administering to the site a therapeutically effective amount of a local anesthetic in the form of a pharmaceutically acceptable composition of claim 12.16. A device for orthopedic restoration or tissue regeneration comprising a block copolymer of formula X, formula Y, or formula Z:RA?[OCH2CH2]f-[POE]g-H??(X), RA?[OCH2CH2]f-[POE]g-[OCH2CH2]h?ORB??(Y), H?A-[POE]g-[OCH2CH2]h-[POE]j-H??(Z), where:RA is C1-C4 alkyl; RB is C1-C4 alkyl; f and h are independently an integer from 2 to 1000; g and j are independently an integer from 2 to 200; POE is a poly(ortho ester) unit of formula IA or formula IIA: whereR* is a C1-C4 alkyl; R is a bond, ?(CH2)?, or ?(CH2)b?O?(CH2)c?; where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5; and each A is independently selected from R1, R2, R3, and R4, where R1 is: