Composition for the treatment of cystic fibrosis
The present invention provides a composition comprising at least one prostacyclin or prostacyclin analog or a pharmaceutically acceptable salt thereof and at least one phosphodiesterase (PDE) 4 inhibitor and optionally a further PDE inhibitor for use in preventing or treating cystic fibrosis by selectively increasing the cAMP levels in bronchoepithelial cells.
1. A method of treating cystic fibrosis by improving conductance of chloride by cystic fibrosis transmembrane conductance regulator (CFTR), comprising the step of administering a composition comprising treprostinil or a pharmaceutically acceptable salt, or derivative thereof and at least one phosphodiesterase (PDE) 4 inhibitor to a subject in need thereof to improve conductance of chloride by CFTR in the subject.
2. The method of claim 1 , wherein said PDE4 inhibitor is selected from the group consisting of Ro 20-1724, Ibudilast, Roflumilast and its N-Oxide, Cilomilast, BAY 19-8004, CC3, AWD 12-281, SCH 351591, Ciclamilast, Piclamilast, CGH2466, Mesembrine, Rolipram, Luteolin and Drotaverine.
3. The method of claim 2 , wherein the PDE4 inhibitor is selected from the group consisting of RO 20-1724, Roflumilast and Ibudilast.
4. The method of claim 1 , further comprising a PDE inhibitor selected from the group consisting of a PDE5 inhibitor, a PDE7 inhibitor and a PDE8 inhibitor.
5. The method of claim 4 , wherein said PDE5 inhibitor is selected from the group consisting of Avanafil, Lodenafil, Mirodenafil, Sildenafil citrate, Tadalafil, Vardenafil and Udenafil.
6. The method of claim 4 , wherein said PDE7 and PDE8 inhibitors are selected from the group consisting of Dipyridamol, BRL50481 and PF-4957325.
7. The method of claim 1 , wherein the composition is formulated as a pharmaceutical composition.
8. The method of claim 7 , wherein the composition is administered by inhalation administration.
9. The method of claim 1 , wherein the composition is administered by a route selected from the group consisting of intravenous administration, subcutaneous administration, and oral administration.
10. The method of claim 9 , wherein the composition is formulated for oral administration in a form selected from the group consisting of a sustained release form, a tablet, and a capsule.
11. The method of claim 2 , wherein the amount of treprostinil or a pharmaceutically acceptable salt, or derivative thereof which is administered is at least 1.0 ng/kg of body weight.
12. The method of claim 1 , wherein the composition comprises treprostinil.
13. The method of claim 1 , wherein the treprostinil derivative is selected from the group consisting of an acid derivative of treprostinil, a prodrug of treprostinil, a polymorph of treprostinil, and an isomer of treprostinil.