Compounds and methods for delivery of prostacyclin analogs
This invention pertains generally to prostacyclin analogs 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. Generally, the compounds and methods of the present invention increase the oral bioavailability and circulating concentrations of treprostinil when administered orally. Compounds of the present invention have the following formula:
1. A method of producing a pharmaceutically acceptable salt of treprostinil comprising dissolving treprostinil in a solvent, adding a base, heating, and cooling in an antisolvent to form a pharmaceutically acceptable salt of treprostinil as a crystalline solid.
2. The method of claim 1 , wherein the base is an inorganic base.
3. The method of claim 2 , wherein the base is an alkali metal.
4. The method of claim 3 , wherein the alkali metal is sodium or potassium.
5. The method of claim 1 , wherein the base is an organic base.
6. The method of claim 5 , wherein the organic base is diethanolamine.
7. The method of claim 3 , wherein the solvent comprises ethanol and water.
8. The method of claim 5 , wherein the solvent comprises ethanol and water.
9. The method of claim 1 , wherein the antisolvent comprises acetone.
10. A pharmaceutically acceptable crystalline salt of treprostinil produced by the method of claim 1 .
11. A pharmaceutical composition prepared by combining a pharmaceutically acceptable salt of treprostinil produced according to the method of claim 1 and a pharmaceutically acceptable carrier.