Treatment of eye disorders with sirtuin modulators

• US 20060292099A1
• Filed: 05/24/2006
• Published: 12/28/2006
• Est. Priority Date: 05/25/2005
• Status: Abandoned Application

• Current Assignee: Sirtris Pharmaceuticals, Inc. (GlaxoSmithKline PLC)
• Original Assignee: Sirtris Pharmaceuticals, Inc. (GlaxoSmithKline PLC)
• Inventors: Livingston, David J., Lambert, Philip, Elliott, Peter, Westphal, Christoph H., Normington, Karl D., Milburn, Michael
• Application Number:
  US11/440,584
• Publication Number:
  US 20060292099A1
• Time in Patent Office: Days
• US Class Current: 424/70.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals

Abstract

Sirtuin modulators, particularly sirtuin activators, are useful in treating vision impairment. In general, the sirtuin modulators inhibit the progression of vision impairment resulting from various eye disorders. The invention also includes pharmaceutically acceptable formulations of sirtuin modulators, particular ophthalmically acceptable formulations.

Claims

1. A composition comprising a cyclodextrin and a sirtuin modulator, or a pharmaceutically acceptable salt, prodrug or a metabolic derivative thereof, wherein when the composition is a liquid and the sirtuin modulator is resveratrol, the composition comprises at least 30 mM of the sirtuin modulator.

2. The compostion of claim 1, wherein the cyclodextrin is a substituted cyclodextrin.

3. The composition of claim 2, wherein the cyclodextrin is substituted on the 2-, 3- or 6-hydroxyl group of a glycopyranose moiety.

4. The composition of claim 2, wherein the cyclodextrin is amorphous.

5. The composition of claim 2, wherein the cyclodextrin is hydroxypropyl-beta-cyclodextrin.

6. The composition of claim 1, wherein the sirtuin modulator is a sirtuin activator.

7. The composition of claim 6, wherein the sirtuin activator is resveratrol, an analog thereof, or a prodrug of resveratrol or the analog.

8. The composition of claim 6, wherein the sirtuin activator is nicotinamide riboside, an analog thereof, or a prodrug of nicotinamide riboside or the analog.

9. The composition of claim 1, wherein the composition is a liquid.

10. The composition of claim 9, wherein the liquid comprises at least 30 mM of the sirtuin modulator.

11. The composition of claim 10, wherein the liquid comprises at least 100 mM of the sirtuin modulator.

12. The composition of claim 1, wherein the composition is a lyophilized powder.

13. A method for treating vision impairment by administering to a patient a therapeutic dosage of a composition comprising cyclodextrin and a sirtuin modulator, or a pharmaceutically acceptable salt, prodrug or a metabolic derivative thereof.

14. A fast melt tablet comprising a sirtuin modulator, or a pharmaceutically acceptable salt, prodrug or a metabolic derivative thereof.

15-20. -20. (canceled)

21. A method for treating vision impairment by administering to a patient a therapeutic dosage of a fast melt tablet comprising a sirtuin modulator, or a pharmaceutically acceptable salt, prodrug or a metabolic derivative thereof.

22. An implanatable device comprising a sirtuin modulator, or a pharmaceutically acceptable salt, prodrug or a metabolic derivative thereof.

23-30. -30. (canceled)

31. A method for treating vision impairment by implanting in a patient a implanatable device comprising a sirtuin modulator, or a pharmaceutically acceptable salt, prodrug or a metabolic derivative thereof.

32. A pharmaceutical composition comprising a micronized sirtuin modulator or a pharmaceutically acceptable salt, prodrug or a metabolic derivative thereof, wherein particles of the micronized sirtuin modulator have an average diameter of less than about 30 microns.

33-38. -38. (canceled)

39. A method for treating vision impairment by administering to a patient a therapeutic dosage of a pharmaceutical composition comprising a micronized sirtuin modulator or a pharmaceutically acceptable salt, prodrug or a metabolic derivative thereof, wherein particles of the micronized sirtuin modulator have an average diameter of less than about 30 microns.