Mixtures of various triblock polyester polyethylene glycol copolymers having improved gel properties
First Claim
1. An aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein:
- (a) an effective amount of a drug; and
(b) a biodegradable polymeric system possessing reverse thermal gelation properties comprising a mixture of at least a Component I triblock copolymer and a Component II triblock copolymer, said triblock copolymers comprising biodegradable polyester A-polymer blocks and polyethylene glycol B-polymer blocks, wherein the B-polymer block of said Component I triblock copolymer has an average molecular weight of 900 to 2000 Daltons and the B-polymer block of said Component II triblock copolymer has an average molecular weight of 600 to 2000 Daltons, and wherein said Component I triblock copolymer has an average molecular weight of between 2500 to 8000 Daltons and said Component II triblock copolymer has an average molecular weight of between 800–
7200 Daltons, and wherein said biodegradable polymeric system is water soluble and contains 51 to 83% by weight of hydrophobic A polymer blocks and 17 to 49% by weight of hydrophilic B polymer blocks and wherein an aqueous solution of said Component I triblock copolymer has a lower gelation temperature than an aqueous solution of said Component II triblock copolymer.
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Abstract
A water soluble, biodegradable reverse thermal gelation system comprising a mixture of at least two types of tri-block copolymer components is disclosed. The tri-block copolymer components are made of a hydrophobic biodegradable polyester A-polymer block and a hydrophilic polyethylene glycol B-polymer block. The drug release and gel matrix erosion rates of the biodegradable reverse thermal gelation system may be modulated by various parameters such as the hydrophobic/hydrophilic component contents, polymer block concentrations, molecular weights and gelation temperatures, and weight ratios of the tri-block copolymer components in the mixture.
90 Citations
21 Claims
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1. An aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein:
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(a) an effective amount of a drug; and (b) a biodegradable polymeric system possessing reverse thermal gelation properties comprising a mixture of at least a Component I triblock copolymer and a Component II triblock copolymer, said triblock copolymers comprising biodegradable polyester A-polymer blocks and polyethylene glycol B-polymer blocks, wherein the B-polymer block of said Component I triblock copolymer has an average molecular weight of 900 to 2000 Daltons and the B-polymer block of said Component II triblock copolymer has an average molecular weight of 600 to 2000 Daltons, and wherein said Component I triblock copolymer has an average molecular weight of between 2500 to 8000 Daltons and said Component II triblock copolymer has an average molecular weight of between 800–
7200 Daltons, and wherein said biodegradable polymeric system is water soluble and contains 51 to 83% by weight of hydrophobic A polymer blocks and 17 to 49% by weight of hydrophilic B polymer blocks and wherein an aqueous solution of said Component I triblock copolymer has a lower gelation temperature than an aqueous solution of said Component II triblock copolymer. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 18, 19, 20, 21)
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9. A method for the administration of a drug to a warm blooded animal in a controlled release form which comprises:
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(1) providing an aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein; (a) an effective amount of a drug; and (b) a biodegradable polymeric system possessing reverse thermal gelation properties comprising a mixture of at least a Component I triblock copolymer and a Component II triblock copolymer, said triblock copolymers comprising biodegradable polyester A-polymer blocks and polyethylene glycol B-polymer blocks, wherein the B-polymer block of said Component I triblock copolymer has an average molecular weight of 900 to 2000 Daltons and the B-polymer block of said Component II triblock copolymer has an average molecular weight of 600 to 2000 Daltons, and wherein said Component I triblock copolymer has an average molecular weight of between 2500 to 8000 Daltons and said Component II triblock copolymer has an average molecular weight of between 800–
7200 Daltons; and
wherein said biodegradable polymeric system is water soluble and contains 51 to 83% by weight of hydrophobic A polymer blocks and 17 to 49% by weight of hydrophilic B polymer blocks and wherein an aqueous solution of said Component I triblock copolymer has a lower gelation temperature than an aqueous solution of said Component II triblock copolymer;(2) maintaining said composition as a liquid at a temperature below the gelation temperature of said biodegradable polymeric system; and (3) administering said composition as a liquid to said warm blooded animal with the subsequent formation of a gel as the temperature of said composition is raised above the gelation temperature of the biodegradable polymeric system by the body temperature of said animal. - View Dependent Claims (10, 11, 12, 13, 14, 15, 16, 17)
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Specification