Ocular therapy using sirtuin-activating agents

• US 20070212395A1
• Filed: 03/08/2006
• Published: 09/13/2007
• Est. Priority Date: 03/08/2006
• Status: Abandoned Application

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Yang, Rong, Donello, John, Schweighoffer, Fabien, WoldeMussie, Elizabeth
• Application Number:
  US11/371,117
• Publication Number:
  US 20070212395A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Ophthalmically therapeutic compositions, such as polymeric drug delivery systems, include a therapeutic component that includes a sirtuin-activating agent, such as resveratrol, which, upon delivery to the posterior segment of a mammalian eye, treats ocular conditions. Methods of making and using the present compositions are also described.

Claims

1. An intraocular implant, comprising:

a sirtuin-activating agent; and

a bioerodible polymer matrix that releases the sirtuin-activating agent at a rate effective to sustain release of an amount of the sirtuin-activating agent from the implant for at least about one week after the implant is placed in an eye.

2. The implant of claim 1, wherein the sirtuin-activating agent is selected from the group consisting of flavones, stilbenes, flavanones, isoflavones, catechins, chalcones, tannins, anthocyanidins, analogs thereof, and derivatives thereof.

3. The implant of claim 1, wherein the sirtuin-activating agent is selected from the group consisting of resveratrol, butein, piceatannol, isoliquiritgenin, fisetin, luteolin, 3,6,3′

4′

-tetrahydroxyflavone, quercetin, analogs thereof, and derivatives thereof.

4. The implant of claim 1, wherein the bioerodible polymer matrix is selected from the group consisting of poly (lactide-co-glycolide) polymer (PLGA), poly-lacetic acid (PLA), poly-glycolic acid (PGA), polyesters, poly (ortho ester), poly (phosphazine), poly (phosphate ester), poly (D,L-lactide-co-glycolide), polyesters, polycaprolactones, gelatin, and collagen, and derivatives and combinations thereof.

5. The implant of claim 1, further comprising an additional ophthalmically acceptable therapeutic agent.

6. The implant of claim 1, wherein the sirtuin-activating agent is dispersed within the bioerodible polymer matrix.

7. The implant of claim 1, wherein the bioerodible polymer matrix comprises a poly (lactide-co-glycolide).

8. The implant of claim 1, wherein the bioerodible polymer matrix comprises a poly (D,L-lactide-co-glycolide).

9. The implant of claim 1, wherein the bioerodible polymer matrix releases sirtuin-activating agent at a rate effective to sustain release of an amount of the sirtuin-activating agent from the implant for more than one month from the time the implant is placed in the vitreous of the eye.

10. The implant of claim 1, wherein the sirtuin-activating agent is resveratrol, and the matrix releases resveratrol at a rate effective to sustain release of a therapeutically effective amount of the resveratrol for a time from about two months to about six months.

11. The implant of claim 1, wherein the implant is structured to be placed in the vitreous of the eye.

12. The implant of claim 1, wherein the sirtuin-activating agent is resveratrol provided in an amount from about 40% by weight to about 70% by weight of the implant, and the biodegradable polymer matrix comprises a poly (lactide-co-glycolide) in an amount from about 30% by weight to about 60% by weight of the implant.

13. The implant of claim 1, formed as a rod, a wafer, or a particle.

14. The implant of claim 1, formed by an extrusion process.

15. The implant of claim 1, wherein the sirtuin-activating agent contains particles comprising resveratrol in solid form.

16-29. -29. (canceled)