Thermosensitive biodegradable polymers based on poly(ether-ester)block copolymers

摘要

A system and method for the parenteral delivery of a drug in a biodegradable polymeric matrix to a warm blooded animal as a liquid with the resultant formation of a gel depot for the controlled release of the drug. The system comprises an injectable biodegradable block copolymeric drug delivery liquid having reverse thermal gelation properties. The delivery liquid is an aqueous solution having dissolved or dispersed therein an effective amount of a drug intimately contained in a biodegradable block copolymer matrix. The copolymer has a reverse gelation temperature below the body temperature of the animal to which it is administered and is made up of (i) a hydrophobic A polymer block comprising a member selected from the group consisting of poly( alpha -hydroxy acids) and poly(ethylene carbonates) and (ii) a hydrophilic B polymer block comprising a polyethylene glycol. Prior to use the liquid is maintained at a temperature below the reverse gelation temperature of the block copolymer. The liquid is parenterally administered into the animal by intramuscular, intraperitoneal, subcutaneous or similar injection with the liquid forming a gel depot of the drug and biodegradable block polymer as the temperature of the liquid is raised by the body temperature of the animal the reverse gelation temperature of the block copolymer. The drug is released at a controlled rate from the copolymer which biodegrades into non-toxic products. The degradation rate can be adjusted by proper selection of the poly( alpha -hydroxy acid) utilized in forming the biodegradable hydrophilic A block.