Christy Lin Shaffer, 668231 Glynmorgan Way, Chapel Hill, NC 27516

5968913, Oct 19, 1999

Dec 23, 1997

8/996740

Karol K. LaCroix - Holly Springs NC
Christy L. Shaffer - Chapel Hill NC
Karla M. Jacobus - Carey NC
Janet L. Rideout - Raleigh NC
David J. Drutz - Chapel Hill NC
Richard C. Evans - Carey NC
William Pendergast - Durham NC

Inspire Pharmaceuticals, Inc. - Durham NC

A61K 908
A61K 3170

514 47

Novel pharmaceutical compositions of uridine 5'-triphosphate (UTP) for use in promoting increased mucociliary clearance of retained mucous secretions of the human airways, middle/inner ears or sinuses are disclosed. Novel Formulation I comprises UTP and aqueous solution having a therapeutic concentration between 5 and 45 mg/mL, a controlled tonicity within the range of 250 to 100 mOsM, a pH between 7. 0 and 7. 5, and is sterile. The pH-adjusted composition is capable of long-term storage in the refrigerated state with a shelf life of up to 30 months. Formulation I may be delivered therapeutically either in a nebulized form or in a liquid form. Novel Formulation II comprises UTP in an aqueous solution or suspension having a therapeutic concentration approaching the limit of UTP's solubility at ambient temperature. This high concentration allows delivery of a therapeutic amount of UTP in very small volumes (50 to 100. mu. L) suitable for administration via portable hand-held devices such as metered dose inhalers.

5962432, Oct 5, 1999

Jul 3, 1996

8/675555

Karol La Croix - Cary NC
Christy Shaffer - Chapel Hill NC
Karla Jacobus - Cary NC
Janet Rideout - Raleigh NC
David Drutz - Chapel Hill NC

Inspire Pharmaceuticals, Inc. - Durham NC

A61K 3170

514 47

A novel formulation of uridine 5'-triphosphate (UTP) for use in promoting increased mucociliary clearance of retained mucous secretions of the human airways, middle/inner ears, or sinuses is disclosed. The composition comprises UTP and aqueous solution having a therapeutic concentration between 5 and 35 mg/mL, which has controlled tonicity within the range of 250 to 1000 mOsM, pH-adjusted, having pH between 7. 0 and 7. 5; and sterile. The pH-adjusted formulation is capable of long-term storage in the refrigerated state, with a shelf life of up to 30 months if kept refrigerated at 5. degree. C. The formulation is delivered therapeutically either in a nebulized form using any of several commercially available nebulizers (e. g. , jet, ultrasonic, etc. ), or in liquid form.

6159952, Dec 12, 2000

Nov 7, 1996

8/744367

Christy L. Shaffer - Chapel Hill NC
Richard C. Boucher - Chapel Hill NC
Janet L. Rideout - Raleigh NC
Karla M. Jacobus - Cary NC

Inspire Pharmaceuticals, Inc. - Durham NC

A61K 3170

514 47

A method of promoting clearance of retained mucous secretions in the bronchi, bronchioles and small terminal airways of a subject in need of such treatment is disclosed. The method comprises administering to the bronchi of the subject a uridine phosphate such as uridine 5'-triphosphate (UTP), or P. sup. 1,P. sup. 4 -di(uridine-5') tetraphosphate (U. sub. 2 P. sub. 4), an analog of UTP, or any other analog, in an amount effective to promote mucociliary clearance and/or cough clearance of retained fluid in the bronchi, bronchioles and small terminal airways. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: aerosol inhalation, any liquid suspension (including nasal drops or spray), oral form (liquid or pill), injected, intra-operative instillation or suppository form.