Pharmaceutical Discovery Corporation

Mannkind Corporation

Christopher A Rhodes

Solomon S Steiner

Gregory S Shen

Robert Feldstein

R Tyler McCabe

Huiling Lian

Bruce F DeCosta

Bryan R Wilson

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

Microparticles for lung delivery comprising diketopiperazine

Muscarinic M.sub.2 receptor ligands are described which are suitable for the treatment of neurological disorders, and which may be administered with minimal side-effects. A method of synthesis of these compounds is also described.

M.sub.2 receptor ligand for the treatment of neurological disorders

Conjugates of fluorescent labels with specific, selective, and high affinity ligands for receptors have been synthesized and used to directly measure binding to receptors.

Fluorescent ligands

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.

Growing community of inventors

Stamford, CT, United States of America

Christopher A Rhodes