Macromed Incorporated

Amgen Inc.

Younsik Cha

Young Kweon Choi

David S Collins

You Han Bae

David Brems

Chaul Min Pai

The invention relates to stable compositions of proteins and related methods wherein a protein capable of transitioning into the molten globular state is contacted with a negatively charged lipid vesicle, thereby stabilizing the protein against thermally-induced aggregation, denaturation, and loss of activity. The protein:phospholipid complex directly stabilizes the secondary and tertiary structure of the protein, and the compositions are useful in high temperature formulations and in novel delivery vehicles.

Stable protein: phospholipid compositions and methods

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.

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

Peptide/protein biodegradable drug delivery devices are prepared as microspheres without the use of solvents by a polymer melt process. A melt of thermostable polypeptides and an appropriate low melting block copolymer mixture is prepared and dispersed in an appropriate fluid medium such as air, water or an immiscible organic fluid without using any organic solvent to form microdroplets. The fluid medium is cooled to solidify the microdroplets into microspheres and then collected and purified or further processed as drug delivery devices. These biodegradable microspheres are suitable as implantable or injectable pharmaceutical formulations. Following administration as solid microspheres into the body of a warm blooded animal, the formulations absorb water from the body to form a hydrogel from which the polypeptide is released continuously over an extended period of time.

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Salt Lake City, UT, United States of America

Younsik Cha