Methods of ophthalmic administration

• US 6,378,526 B1
• Filed: 08/03/1998
• Issued: 04/30/2002
• Est. Priority Date: 08/03/1998
• Status: Expired due to Term

• Current Assignee: Sun Pharma Global Fze (Sun Pharmaceutical Industries Limited)
• Original Assignee: Insite Vision Incorporated (Daiichi Sankyo Company Limited)
• Inventors: Hecker, Karl L., Clark, Leslie A., Pfeiffer, James F., Bowman, Lyle M.
• Primary Examiner(s): McDermott, Corrine
• Assistant Examiner(s): Barrett, Thomas C.
• Application Number:
  US09/127,920
• Time in Patent Office: 1,366 Days
• Field of Search: 604/521, 128/898
• US Class Current: 128/898
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/12 for cataracts
• 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
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/904 for medical, immunological, body treatment, or diagnosis
• CPC Class Codes: Y10S 977/906 Drug delivery
• CPC Class Codes: Y10S 977/908 Mechanical repair performed/surgical

Abstract

Intrascleral injection of a therapeutic or diagnostic material at a location overlying the retina provides a minimally invasive technique for delivering the agent to the posterior segment of the eye. The procedure also allows for close proximity of the material to the targeted site and can be effectively used to treat conditions associated with the posterior segment of the eye, including macular degeneration, vein occlusion, and diabetic retinopathy.

Claims

1. A method of intrascleral injection, which comprises:

injecting with a cannula an effective amount of a therapeutic or diagnostic material into the scleral layer of an eye;

wherein said cannula is inserted through a location on an exterior surface of the sclera over the posterior segment of the eye.

2. The method according to claim 1, further comprising inserting said cannula into said scleral layer in a substantially rotational direction.

3. The method according to claim 1, wherein said cannula is inserted into said scleral layer a distance greater than the thickness of the sclera at the location of insertion.

4. The method according to claim 1, wherein said insertion is carried out using a guided injection device.

5. The method according to claim 2, wherein said cannula is inserted at an insertion angle of less than about 60 degrees.

6. The method according to claim 5, wherein said cannula is inserted at an insertion angle of from about 20 to 40 degrees.

7. The method according to claim 2, wherein said cannula is inserted in a fail safe orientation.

8. The method according to claim 1, wherein the amount of material injected is at least 0.1 μ

l.

9. The method according to claim 8, wherein the amount of material injected is within the range of about 3 to about 25 μ

l.

10. The method according to claim 1, wherein the material is injected at a rate of from about 0.1 to about 3.0 μ

l/s.

11. The method according to claim 1, wherein the material comprises a pharmaceutically active agent and an ophthalmologically acceptable carrier.

12. The method according to claim 11, wherein said ophthalmologically acceptable carrier is water or oil.

13. The method according to claim 11, wherein said pharmaceutically active agent is selected from the group consisting of metalloproteinase inhibitors, vascular endothelium growth factor regulating agents, fibroblast growth factor regulating agents, integrin blockers, protein kinase C inhibitors, endogenous angiogenesis inhibitors, calcium channel blockers, NMDA receptor antagonists, AMPA receptor antagonists, antioxidants, peroxidation inhibitors, apoptosis inhibitors, adenosine or adenosine regulating agents, nitric oxide regulating agents, anti-inflammatory agents, antiviral agents, antibiotics;

antitumor agents, anti-cataract agents, anti-glaucoma agents, anesthetics, antibodies and fragments thereof, antisense compounds, ribozymes, and triplex nucleic acids.

14. The method according to claim 11, wherein said material further comprises a biodegradable polymer matrix.

15. The method according to claim 1, wherein said injection is made posteriorly to the equator of the eye.

16. The method according to claim 15, wherein said location of said insertion substantially overlies the macula or its immediate vicinity.

17. The method according to claim 1, further comprising, making an incision in a conjunctival layer and passing said cannula through said incision, prior to said injecting step.

18. The method according to claim 1, wherein the terminal end of said cannula penetrates a conjunctival layer before entering said scleral layer.

19. The method according to claim 1, further comprising repeating said injecting at one or more locations on said scleral layer.

20. The method according to claim 1, wherein said eye is suffering from an ocular disease and said material is a therapeutic material effective for treating said disease.

21. The method according to claim 20, wherein said disease is selected from the group consisting of cystoid macular edema, age-related macular degeneration, diabetic retinopathy, diabetic maculopathy, central retinal artery occlusion, central retinal vein occlusion, branch retinal artery occlusion, branch retinal vein occlusion, retinopathy of prematurity, sickel cell retinopathy, photic retinopathy, radiation retinopathy, retinal detachment, retinitis pigmentosa, macular hole, cataract, and glaucoma.

22. The method according to claim 21, wherein said disease is diabetic retinopathy and said therapeutic material comprises an anti-angiogenesis agent.

23. The method according to claim 21, wherein said disease is glaucoma.

24. A method for treating macular degeneration, which comprises injecting an effective macular degenerative treating amount of an agent into the sclera of an eye in need of treatment thereof through a location on the exterior surface of the sclera over the posterior segment of the eye.

25. The method according to claim 24, wherein said anti-macular degenerative agent is selected from the group consisting of antisense compounds of VEGF, antibodies of VEGF, a fragment of an antibody of VEGF, triplex nucleic acids of VEGF, receptor blockers for VEGF, ribozymes for VEGF and antioxidants.

26. The method according to claim 24, wherein said agent is injected into a portion of the sclera that substantially overlies the macula or its immediate vicinity.

27. A method for treating a condition in the eye involving neovascularization, which comprises injecting into the sclera, through a location on the exterior surface of the sclera over the posterior segment of the eye, an effective neovascularization reducing or preventing amount of an anti-angiogenesis agent.

28. The method according to claim 27, wherein said agent is selected from the group consisting of metalloproteinase inhibitors, VEGF regulating agents, FGF regulating agents, integrin blockers, and protein kinase C inhibitors.

29. The method according to claim 27, wherein said condition is diabetic retinopathy.