Pharmaceutical Discovery Corporation

Other

Mannkind Corporation

Gregory S Shen

Solomon S Steiner

Christopher A Rhodes

Robert Feldstein

Huiling Lian

Baldomero M Olivera

Craig S Walker

Elsie C Jimenez

Jean E Rivier

Robert M Jones

J Michael McIntosh

David R Hillyard

Lourdes J Cruz

Maren Watkins

R Tyler McCabe

Li-Ming Zhou

Richard T Layer

Reshma Shetty

Clark Colledge

Fe C Abogadie

Drug delivery to the pulmonary system has been achieved by encapsulation of the drug to be delivered in microparticles having a size range between 0.5 and ten microns, preferably in the range of two to five microns, formed of a material releasing drug at a pH of greater than 6.4. In a preferred embodiment, the drug delivery system is based on the formation of diketopiperazine microparticles which are stable at a pH of 6.4 or less and unstable at pH of greater than 6.4, or which are stable at both acidic and basic pH, but which are unstable at pH between about 6.4 and 8. Other types of materials can also be used, including biodegradable natural and synthetic polymers, such as proteins, polymers of mixed amino acids (proteinoids), alginate, and poly(hydroxy acids). In another embodiment, the microparticles have been modified to effect targeting to specific cell types and to effect release only after reaching the targeted cells.

Method for drug delivery to the pulmonary system

The invention relates to relatively short peptides (termed I-conotoxins herein), about 30-50 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include four disulfide bonds.

I-superfamily conotoxins

The present invention is directed to conantokin peptides, conantokin peptide derivatives and conantokin peptide chimeras, referred to collectively as conantokins, having 10-30 amino acids, including preferably two or more &ggr;-carboxyglutamic acid residues. The conantokins are useful for the treatment of neurologic and psychiatric disorders, such as anticonvulsant agents, neuroprotective agents or analgesic agents.

Conantokins

Microparticles for lung delivery comprising diketopiperazine

Drug delivery systems have been developed based on the formation of diketopiperazine (or analogs) microparticles. In the preferred embodiment the microparticle is stable at low pH and disintegrates at physiological pH, and is particularly useful for oral drug delivery. In other embodiments, the microparticles are stable at high pH and disintegrate at neutral or basic pH, or are stable at neutral pH and disintegrate at high or low pH. In the most preferred embodiment the microparticles are formed in the presence of the drug to be delivered, for example, insulin, felbamate, calcitonin or heparin. The diketopiperazine synthetic intermediates are preferably formed by cyclodimerization to form diketopiperazine derivatives at elevated temperatures under dehydrating conditions, functionalized on the side chains, and then precipitated with drug to be incorporated into microparticles.

Method for making self-assembling diketopiperazine drug delivery system

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Hartsdale, NY, United States of America

Gregory S Shen