Pharmaceutical formulations of xanthine or xanthine derivatives, and their use

1. A method for treating a fibrotic disease in a subject in need thereof, comprising locally administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical formulation, the formulation comprising:

(a) a quantity of a compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein

each of R 1 , R 2 and R 3 is independently selected from the group consisting of H, a C 1 -C 6 alkyl, a C 2 -C 6 alkenyl, a C 2 -C 6 alkynyl, a cycloalkyl, a heterocyclyl, an aryl, and heteroaryl, each of which is optionally substituted; and

(b) a quantity of a polysaccharide selected from the group consisting of hyaluronic acid, heparin, heparan, chondroitin, dermatan, keratin, and pharmaceutically acceptable water-soluble salts thereof.

2. The method of claim 1 , wherein each of R 1 , R 2 and R 3 is independently selected from the group consisting of H and an optionally substituted C 1 -C 6 alkyl.

3. The method of claim 1 , wherein the compound of formula I is selected from the group consisting of pentoxifylline, caffeine, aminophylline, enprofylline, isbufylline, theophylline, theobromine, and 3-isobutyl-1-methylxanthine.

4. The method of claim 1 , wherein the fibrotic disease is Peyronie's disease.

5. The method of claim 1 , wherein administration of the formulation leads to improvement of erectile dysfunction.

6. The method of claim 1 , wherein the pharmaceutical formulation has a pH of between 5.5 and 6.

7. The method of claim 1 , wherein the therapeutically effective amount is between 4 mg and 20 mg.

8. The method of claim 1 , wherein the pharmaceutical formulation is administered locally to the penis of the subject.

9. The method of claim 8 , wherein the pharmaceutical formulation is administered by intracavernosal injection.

10. The method of claim 1 , wherein the pharmaceutical formulation further comprises a second active agent selected from the group consisting of alprostadil, papaverine, and phentolamine.

11. The method of claim 1 , wherein the pharmaceutical formulation further comprises a collagenase.

12. A pharmaceutical formulation comprising a therapeutically effective amount of a compound of formula I:

or a pharmaceutically acceptable salt, ester, amide or prodrug thereof; a quantity of a polysaccharide selected from the group consisting of hyaluronic acid, heparin, heparan, chondroitin, dermatan, keratin, and pharmaceutically acceptable water-soluble salts thereof; and a pharmaceutically acceptable excipient or carrier suitable for local administration,

wherein each of

R 1 , R 2 and R 3 is independently selected from the group consisting of H, a C 1 -C 6 alkyl, a C 2 -C 6 alkenyl, a C 2 -C 6 alkynyl, a cycloalkyl, a heterocyclyl, an aryl, and heteroaryl, each of which is optionally substituted.

13. The formulation of claim 12 , wherein each of R 1 , R 2 and R 3 is independently selected from the group consisting of H a C 1 -C 6 alkyl, and a substituted C 1 -C 6 alkyl.

14. The formulation of claim 12 wherein the compound of formula I is selected from the group consisting pentoxifylline, caffeine, aminophylline, enprofylline, isbufylline, theophylline, theobromine, and 3-isobutyl-1-methylxanthine.

15. The formulation of claim 12 , having a pH of between 5.5 and 6.

16. The formulation of claim 12 , wherein the therapeutically effective amount is between 4 mg and 20 mg.

17. The formulation of claim 12 , further comprising a sterile liquid composition and wherein the excipient or carrier is suitable for intracavernosal injection.

18. The pharmaceutical formulation of claim 12 , further comprising an additional active agent selected from the group consisting of alprostadil, papaverine, and phentolamine.

19. The pharmaceutical formulation of claim 12 , further comprising a collagenase.

20. The pharmaceutical formulation of claim 12 , further comprising an active agent selected from the group consisting of at least one anesthetic, at least one anti-bacterial agent, at least one antiviral medicament, at least one antifungal medicament and combinations thereof.

21. The pharmaceutical formulation of claim 20 , wherein the anesthetic is selected from the group consisting of lidocaine, tetracaine, proparacaine, procaine, dyclonine and combinations thereof.

22. The formulation of claim 12 , wherein the formulation is ensconced within essentially spherical particles fabricated of a water soluble biodegradable polymer selected from the group consisting of poly(lactic acid-co-glycolic acid), poly(lactic acid), poly(glycolic acid), poly(caprolactone), and poly(hydroxybutyrate).

23. A pharmaceutical composition comprising essentially spherical particles incorporating a therapeutically effective amount of a compound of formula I:

or a pharmaceutically acceptable salt, ester, amide or prodrug thereof and a pharmaceutically acceptable excipient or carrier suitable for local administration, wherein

each of R 1 , R 2 and R 3 is independently selected from the group consisting of H, a C 1 -C 6 alkyl, a C 2 -C 6 alkenyl, a C 2 -C 6 alkynyl, a cycloalkyl, a heterocyclyl, an aryl, and heteroaryl, each of which is optionally substituted,

wherein the particles are fabricated of a water soluble biodegradable polymer selected from the group consisting of poly(lactic acid-co-glycolic acid), poly(lactic acid), poly(glycolic acid), poly(caprolactone), and poly(hydroxybutyrate).