Sustained release composition of prostacyclin

1. A pharmaceutical composition comprising:

a treprostinil carrier-linked prodrug; and

optionally one or more pharmaceutically acceptable excipients;

wherein the concentration of the treprostinil carrier-linked prodrug is sufficient to maintain a therapeutically effective level of treprostinil in blood plasma for at least 12 hours after a single subcutaneous or intramuscular injection; and

wherein the treprostinil carrier-linked prodrug comprises:

a treprostinil drug; and

a promoiety, which promoiety comprises:

a carrier;

a reversible prodrug linker moiety; and

optionally one or more spacer moieties;

wherein one end of the reversible prodrug linker moiety is attached to the treprostinil through a reversible linkage;

wherein another end of the reversible prodrug linker moiety is attached through a permanent bond to either a spacer moiety permanently attached to the carrier moiety, or is directly attached through a permanent bond to the carrier moiety; and

wherein the prodrug linker moiety is non-enzymatically hydrolytically degradable.

2. The pharmaceutical composition of claim 1 ;

wherein the pharmaceutical composition comprises the treprostinil carrier-linked prodrug in a concentration of at least 0.05 mg/ml.

3. The pharmaceutical composition of claim 2 ;

wherein a single dose of the pharmaceutical composition comprises at least 0.05 mg of the treprostinil carrier-linked prodrug.

4. The pharmaceutical composition of claim 1 ;

wherein the time period between administration of a pharmaceutical composition is at least about 12 hours.

5. The pharmaceutical composition of claim 1 ;

wherein the pharmaceutical composition has a pharmacokinetic profile in vivo in a mammal with substantially no burst of the treprostinil carrier-linked prodrug.

6. The pharmaceutical composition of claim 1 ;

wherein the pharmaceutical composition is characterized by exhibiting a peak to trough ratio of the in a mammal of less than 5.

7. The pharmaceutical composition of claim 1 ;

wherein the treprostinil carrier-linked prodrug has an activity of <20% of the activity of free treprostinil.

8. The pharmaceutical composition of claim 1 ;

wherein, after subcutaneous or intramuscular administration of said treprostinil carrier-linked prodrug, more than 50% of the administered treprostinil dose is releasable within the blood compartment.

9. The pharmaceutical composition of claim 1 ;

wherein the promoiety of the prodrug comprises a linear or branched PEG moiety.

10. The pharmaceutical composition of claim 1 ;

wherein the treprostinil carrier-linked prodrug has an activity of <5% of the activity of free treprostinil.

11. A method for treating pulmonary hypertension, wherein the method comprises the step of:

subcutaneous or intramuscular administration, to a patient with pulmonary hypertension, of pharmaceutical composition of claim 1 ;

wherein the pharmaceutical composition releases therapeutically effective amounts of free treprostinil compound for a period of time of at least 12 hours.

12. The method of claim 11 ;

wherein the pharmaceutical composition of (b) comprises from about 0.05 to about 10 weight percent the treprostinil carrier-linked prodrug and from about 0.5 to about 20 weight percent total polymer content.

13. The pharmaceutical composition of claim 1 ;

wherein the pharmaceutical composition is characterized by exhibiting a peak to trough ratio of the treprostinil carrier-linked prodrug in a mammal of less than 2.