Ocular solutions

• US 7,087,237 B2
• Filed: 09/19/2003
• Issued: 08/08/2006
• Est. Priority Date: 09/19/2003
• Status: Expired due to Fees

• Current Assignee: Gholam A. Peyman
• Original Assignee: Advanced Ocular Systems Limited (IFS Construction Services Ltd.)
• Inventors: Peyman, Gholam
• Primary Examiner(s): Sheikh, Humera N.
• Application Number:
  US10/667,161
• Publication Number:
  US 20050063996A1
• Time in Patent Office: 1,054 Days
• Field of Search: 424/400, 424/422, 424/423, 424/427, 424/428
• US Class Current: 424/400
• 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 31/365 Lactones
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7052 having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
• 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 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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

Containing at least one macrolide antibiotic and/or mycophenolic acid provide anti-inflammatory, anti-cell proliferation, anti-cell migration, anti-angiogenesis, antimicrobial, and antifungal effects. In one embodiment, the solution is administered intraocularly after cataract surgery before insertion of a replacement intraocular lens, resulting in reduced posterior capsular opacification which may eliminate the need for a subsequent surgery. The solution may be one that is invasively administered, for example, an irrigation or volume replacement solution containing at least one macrolide antibiotic such as tacrolimus, sirolimus, everolimus, cyclosporine, and ascomycin, or mycophenolic acid. The solution may be one that is non-invasively or topically administered in the form of drops, ointments, gels, creams, etc. and may include eye lubricants and contact lens solutions.

Claims

1. A therapeutic method comprising providing to an eye of a patient a physiologic ophthalmic irrigating or volume replacement solution containing at least one of a macrolide antibiotic or mycophenolic acid at a concentration in the range between about 1 ng/ml to about 200 μ

g/ml to provide irrigation, wash, or volume replacement, further providing an anti-inflammatory effect without increased intraocular pressure.

2. The method of claim 1 wherein the macrolide antibiotic or mycophenolic acid provides at least one selected from the group consisting of an anti-inflammatory effect, an anti-cell proliferation effect, an anti-cell migration effect, an anti-angiogenesis effect, an antimicrobial effect, and an antifungal effect.

3. The method of claim 1 wherein the macrolide antibiotic or mycophenolic acid further provides an anti-angiogenic effect in a patient with an ocular tumor, a patient with diabetes, or a patient with sickle cell anemia.

4. The method of claim 1 wherein the macrolide antibiotic or mycophenolic acid is at a concentration of about 1 μ

g/ml.

5. The method of claim 1 wherein the macrolide antibiotic or mycophenolic acid is at a concentration ranging from about 1 ng/ml to about 20 μ

g/ml.

6. The method of claim 1 wherein the macrolide antibiotic or mycophenolic acid is at a concentration ranging from about 20 μ

g/ml to about 200 μ

g/ml.

7. A therapeutic method comprising intraocularly administering to a patient undergoing cataract surgery an ocular solution containing at least one of a macrolide antibiotic or mycophenolic acid at a concentration in the range from about 20 μ

g/ml to about 200 μ

g/ml within a lens capsule prior to insertion of a replacement intraocular lens.

8. The method of claim 7 wherein the solution reduces opacification of the posterior capsule.

9. The method of claim 7 wherein the macrolide antibiotic is formulated as at least one selected from the group consisting of a liposome, a macrosphere, a microsphere, a macrocapsule, a microcapsule, a macrovesicle, and a microvesicle.

10. The method of claim 7 wherein the macrolide antibiotic or mycophenolic acid is at a concentration in the range of about 20 μ

g/ml to about 200 μ

g/ml.

11. The method of claim 9 wherein the macrolide antibiotic or mycophenolic acid is implanted within the capsule.

12. An article comprising an implantable ocular replacement lens in a solution containing a concentration of a macrolide antibiotic or mycophenolic acid ranging from about 20 μ

g/ml to about 2000 μ

g/ml sufficient to provide the lens with at least one effect selected from the group consisting of anti-cell proliferation, anti-cell migration, anti-inflammatory, anti-angiogenesis, antimicrobial, and antifungal.

13. The article of claim 12 wherein the concentration is the range between about 20 μ

g/ml to about 200 μ

g/ml.

14. The article of claim 12 wherein the macrolide antibiotic is at least one selected from the of tacrolimus, cyclosporine, sirolimus, everolimus, ascomycin, erythromycin, azithromycin, clarithromycin, clindamycin, lincomycin, dirithromycin, josamycin, spiramycin, diacetyl-midecamycin, tylosin, roxithromycin, ABT-773, telithromycin, leucomycins, and lincosamide.

15. An article comprising an implantable ocular replacement lens containing at least one macrolide antibiotic or mycophenolic acid at a concentration ranging from about 20 μ

g/ml to about 2000μ

g/ml.

16. The article of claim 15 wherein the antibiotic or mycophenolic acid is in a solution in which the lens is contained.

17. The article of claim 15 wherein the lens is a porous hydrogel and the antibiotic or mycophenolic acid is within the pores of the hydrogel lens.

18. The article of claim 15 wherein the antibiotic or mycophenolic acid is in a coating on at least one lens surface.

19. The article of claim 15 wherein the lens is implanted in a lens capsule and the implanted lens releases the antibiotic or mycophenolic acid in the lens capsule.

20. The article of claim 15 wherein the macrolide antibiotic is at least one selected from the group consisting of tacrolimus, cyclosporine, sirolimus, everolimus, ascomycin, erythromycin, azithromycin, clarithromycin, clindamycin, lincomycin, dirithromycin, josamycin, spiramycin, diacetyl-midecamycin, tylosin, roxithromycin, ABT-773, telithromycin, leucomycins, and lincosamide.

21. An article comprising an implantable ocular lens in an ophthalmically acceptable medium, the medium further comprising an effective anti-cell proliferative or anti-cell migratory concentration of at least one macrolide antibiotic or mycophenolic acid ranging from about 20 μ

g/ml to about 2000 μ

g/ml.

22. The article of claim 21 wherein the concentration is in the range between about 200 μ

g/ml to about 2000 μ

g/ml.

23. The article of claim 21 wherein the concentration is in the range between about 20 μ

g/ml to about 200 μ

g/ml.

24. The article of claim 21 wherein the macrolide antibiotic is at least one selected from the group consisting of tacrolimus, cyclosporine, sirolimus, everolimus, ascomycin, erythromycin, azithromycin, clarithromycin, clindamycin, lincomycin, dirithromycin, josamycin, spiramycin, diacetyl-midecamycin, tylosin, roxithromycin, ABT-773, telithromycin, leucomycins, and lincosamide.