Compounds and methods for delivery of prostacyclin analogs
This invention pertains generally to prostacyclin formulations and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis.
1. A method of treating pulmonary hypertension comprising intravenously administering to a human suffering from pulmonary hypertension a formulation for intravenous administration comprising a therapeutically effective amount of treprostinil or a pharmaceutically acceptable salt or ester thereof and a diluent selected from the group consisting of sterile water, isotonic aqueous saline solution, and 5% dextrose solution.
2. The method of claim 1 , wherein the therapeutically effective amount of treprostinil in the formulation is in the form of an ester.
3. The method of claim 2 , wherein the ester is a compound of formula:
wherein,
R 1 is independently selected from the group consisting of H, substituted and unsubstituted benzyl groups, and groups wherein OR 1 are substituted or unsubstituted glycolamide esters;
R 2 and R 3 may be the same or different and are independently selected from the group consisting of H, phosphate and groups wherein OR 2 and OR 3 form esters of amino acids or proteins, with the proviso that all of R 1 , R 2 and R 3 are not H;
an enantiomer of the compound;
and pharmaceutically acceptable salts of the compound and polymorphs of the compound.
4. The method of claim 1 , wherein the therapeutically effective amount of treprostinil in the formulation is in the form of a salt of treprostinil.
5. The method of claim 4 , wherein the therapeutically effective amount of treprostinil in the formulation is in the form of a polymorph of a salt of treprostinil.
6. The method of claim 5 , wherein the polymorph is a polymorph of a diethanolamine salt of treprostinil.
7. The method of claim 1 , wherein the formulation comprises a therapeutically effective amount of treprostinil or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein the diluent consists of sterile water.
9. The method of claim 7 , wherein the diluent consists of isotonic aqueous saline solution.
10. The method of claim 8 , wherein the intravenous administration provides a level of treprostinil bioavailability approximating that from a subcutaneous infusion of treprostinil sodium.
11. The method of claim 9 , wherein the intravenous administration provides a level of treprostinil bioavailability approximating that from a subcutaneous infusion of treprostinil sodium.