Eye treatments using synthetic thyroid hormone compositions

• US 6,555,582 B1
• Filed: 08/10/1999
• Issued: 04/29/2003
• Est. Priority Date: 08/20/1996
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Jumper, Michele D., Scanlan, Thomas S., Schwartz, Daniel M., Baxter, John D.
• Primary Examiner(s): Witz, Jean C.
• Application Number:
  US09/371,592
• Time in Patent Office: 1,358 Days
• Field of Search: 514/568, 424/913, 424/427, 424/428, 424/429
• US Class Current: 514/568
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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

Abstract

The present invention involves the discovery that synthetic thyroid hormones can be used as compositions to reduce intraocular pressure in vivo. Methods of screening synthetic thyroid hormones for effect on intraocular pressure, aqueous pressure, hydraulic conductivity, hyaluronic acid secretion, and extracellular matrix assembly are provided. Methods of treating glaucoma and treating excess intraocular pressure with synthetic thyroid hormones and compositions therefore are also provided.

Claims

1. A method of inhibiting hyaluronic acid secretion in cells in an eye comprising:

topically applying an effective amount of a synthetic thyroid hormone to an eye, thereby inhibiting hyaluronic acid secretion by cells in the eye, wherein said synthetic thyroid hormone at a concentration of 10 micromolar or less inhibits at least 10% of total hyaluronic acid secretion from cultured human trabecular meshwork cells after three days culture at 37°

C. compared to human trabecular meshwork cells cultured in the absence of said synthetic thyroid hormone after three days of culture at 37°

C., and

with the proviso that said non-systemically applying does not include topical application of T3 or T4 isolated from naturally occurring tissues.

2. The method of claim 1, wherein said synthetic thyroid hormone at a concentration of 1 micromolar inhibits at least 10% of total hyaluronic acid secretion in cultured human trabecular meshwork cells.

3. The method of claim 2, wherein said synthetic thyroid hormone at a concentration of 0.1 micromolar inhibits at least 10% of total hyaluronic acid secretion in cultured human trabecular meshwork cells.

4. The method of claim 2, wherein said eye cells are human trabecular meshwork cells.

5. The method of claim 4, wherein said human trabecular meshwork cells are in a trabecular meshwork in an eye.

6. The method of claim 4, wherein said synthetic thyroid hormone is applied with an eye compatible pharmaceutical carrier to an eye.

7. The method of claim 6, wherein said pharmaceutical carrier is an eye compatible saline.

8. The method of claim 6, wherein said synthetic thyroid hormone is in a liposome mixture.

9. The method of claim 6, wherein said synthetic thyroid hormone is located in a synthetic polymer capable of releasing said synthetic polymer by diffusion.

10. The method of claim 1, wherein the synthetic hormone is an esterified synthetic thyroid hormone derivative.

11. The method of claim 1, wherein the synthetic hormone is not an esterified synthetic thyroid hormone derivative.

12. The method of claim 1, wherein the eye is a rabbit, rat, mouse, pig, cat, human, or monkey eye.

13. The method of claim 1, wherein the eye is ex vivo.

14. The method of claim 1, wherein the eye is a diseased eye suffering from glaucoma.

15. The method of claim 1, wherein said topical administration comprises diffusion of the synthetic hormone from an ocular implant or ocular insert.

16. The method of claim 1, wherein said topical administration comprises diffusion of the synthetic hormone from an eye contact impregnated with the synthetic hormone.

17. The method of claim 1, wherein the synthetic thyroid hormone is selected from the group consisting of:

TS1, TS2, TS3, TS5, TS6, TS7, TS8, TS9 and TS10.

18. The method of claim 1, wherein the synthetic thyroid hormone is selected from the group consisting of:

an esterified derivative of TS1, an esterified derivative of TS2, an esterified derivative of TS3, an esterified derivative of TS5, an esterified derivative of TS6, an esterified derivative of TS7, an esterified derivative of TS8, an esterified derivative of TS9 and an esterified derivative of TS10.

19. The method of claim 6, wherein the eye compatible pharmaceutical carrier comprises a biodegradeable synthetic polymer capable of sustained release of the synthetic hormone.

20. The method of claim 6, wherein at least about 0.1 ng to about 20 ng of the synthetic hormone is applied to the eye per day.

21. The method of claim 6, wherein the eye compatible pharmaceutical carrier comprises one or more liposomes.