Compounds and methods for delivery of prostacyclin analogs

Patent metadata

Field	Value
Publication number	US-9278901-B2
Application number	US-201514710694-A
Country	US
Kind code	B2
Filing date	May 13, 2015
Priority date	May 22, 2003
Publication date	Mar 8, 2016
Grant date	Mar 8, 2016

Abstract

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.

First claim

What is claimed is:

1. A method of treating pulmonary hypertension comprising administering to a subject in needed thereof an oral pharmaceutical formulation comprising a pharmaceutically acceptable salt or ester of treprostinil which has an absolute bioavailability of at least 15%, wherein a Cmax in a plasma of the subject increases in a linear fashion with a dose of at least 0.05 mg administered to the subject and wherein a concentration of treprostinil in the plasma of the subject is at least 50 pg/ml for at least 8 hours.

2. The method of claim 1 , wherein the absolute bioavailability of said salt or ester ranges from 21 to 25%.

3. The method of claim 1 , wherein the oral bioavailability of the salt or ester is at least 50% greater than the oral bioavailability of treprostinil as free acid.

4. The method of claim 1 , wherein the oral bioavailability of the salt or ester is at least 100% greater than the oral bioavailability of treprostinil as free acid.

5. The method of claim 1 , wherein the pharmaceutically acceptable salt or ester is the diethanolamine salt of treprostinil.

6. The method of claim 1 , wherein the subject is a human.

7. A method of treating pulmonary hypertension comprising administering to a subject in needed thereof an oral pharmaceutical formulation comprising a pharmaceutically acceptable salt or ester of treprostinil which has an absolute bioavailability of at least 15%, wherein an AUCinf in a plasma of the subject increases in a linear fashion with a dose of at least 0.05 mg administered to the subject and wherein a concentration of treprostinil in the plasma of the subject is at least 50 pg/ml for at least 8 hours.

8. The method of claim 7 , wherein the absolute bioavailability of said salt or ester ranges from 21 to 25%.

9. The method of claim 7 , wherein the oral bioavailability of the salt or ester is at least 50% greater than the oral bioavailability of treprostinil as free acid.

10. The method of claim 7 , wherein the oral bioavailability of the salt or ester is at least 100% greater than the oral bioavailability of treprostinil as free acid.

11. The method of claim 7 , wherein the pharmaceutically acceptable salt or ester is the diethanolamine salt of treprostinil.

12. The method of claim 7 , wherein the subject is a human.

Assignees

• United Therapeutics Corp

Inventors

• Phares Ken
• Mottola David
• Jeffs Roger

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P35/00

  Antineoplastic agents · CPC title