APPARATUS AND FORMULATIONS FOR SUPRACHORIDAL DRUG DELIVERY

• US 20130216623A1
• Filed: 03/15/2013
• Published: 08/22/2013
• Est. Priority Date: 02/22/2006
• Status: Abandoned Application

• Current Assignee: Clearside Biomedical, Inc.
• Original Assignee: iScience Interventional Corporation
• Inventors: Yamamoto, Ronald, Conston, Stanley R., Sierra, David
• Application Number:
  US13/842,218
• Publication Number:
  US 20130216623A1
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61F 9/0026 Ophthalmic product dispenser attachments to facilitate positioning near the eye
• CPC Class Codes: A61F 9/007 Methods or devices for eye surgery
• CPC Class Codes: A61F 9/00736 Instruments for removal of intra-ocular material or intra-ocular injection, e.g. cataract instruments A61F9/008 takes precedence
• CPC Class Codes: A61K 31/717 Celluloses
• CPC Class Codes: A61K 31/718 Starch or degraded starch, e.g. amylose, amylopectin
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61M 2005/3103 Leak prevention means for distal end of syringes, i.e. syringe end for mounting a needle
• CPC Class Codes: A61M 2210/0612 Eyes
• CPC Class Codes: A61M 5/486 Indicating injection pressure

Abstract

Drug formulations, devices and methods are provided to deliver biologically active substances to the eye. The formulations are delivered into scleral tissues adjacent to or into the suprachoroidal space without damage to the underlying choroid. One class of formulations is provided wherein the formulation is localized in the suprachoroidal space near the region into which it is administered. Another class of formulations is provided wherein the formulation can migrate to another region of the suprachoroidal space, thus allowing an injection in the anterior region of the eye in order to treat the posterior region.

Claims

1. A drug formulation characterized by a zero shear viscosity of at least 300,000 mPas for injection into the suprachoroidal space of an eye comprising a biologically active substance and a thixotropic polymeric excipient that acts as a gel-like material to spread after injection and uniformly distribute and localize the drug in a region of the suprachoroidal space.

2. The drug formulation according to claim 1 further characterized by a viscosity of not more than about 400 mPas at 1000 s⁻

1 shear rate.

3. The drug formulation according to claim 1 wherein said gel-like material crosslinks after injection into the suprachoroidal space.

4. The drug formulation according to claim 1 wherein said biologically active substance comprises microparticles or microspheres.

5. The drug formulation according to any one of claims 1 to 4 wherein said polymeric excipient comprises hyaluronic acid, chondroitin sulfate, gelatin, polyhydroxyethylmethacrylate, dermatin sulfate, polyethylene oxide, polyethylene glycol, polypropylene oxide, polypropylene glycol, alginate, starch derivatives, a water soluble chitin derivative, a water soluble cellulose derivative or polyvinylpyrollidone.

8. The drug formulation according claim 4 or 6 wherein the microparticles or microspheres additionally comprise a controlled release coating.

9. The drug formulation according to claim 4 or 6 wherein the microparticles or microspheres additionally comprise a tissue affinity surface.

10. The drug formulation according to any of claim 1 to 4 or 6 wherein the biologically active substance comprises an antibiotic, a steroid, a non-steroidal anti-inflammatory agent, a neuroprotectant, an anti-VEGF agent, or a neovascularization suppressant.

11. The drug formulation of claim 10 wherein the biologically active substance comprises both a steroid and an anti-VEGF agent or neovascular suppressant.

6. A drug formulation for delivery to the suprachoroidal space of an eye comprising a biologically active substance and microspheres or microparticles with an outer diameter in the range of about 1 to 33 microns

7. The drug formulation according to claim 6 further comprising a polymer excipient to uniformly disperse said microspheres or microparticles in the suprachoroidal space.

12. A method for administering drugs to eye comprising placing formulation comprising a biologically active substance and a polymer excipient in the suprachoroidal space such that said excipient gels after delivery to localize said biologically active substance.

13. The method according to claim 12 wherein said formulation is placed in a posterior region of the suprachoroidal space.

14. The method according to claim 12 wherein said formulation is placed in an anterior region of the suprachoroidal space.

18. The method according to any of claims 12 to 17 wherein said formulation comprises a thixotropic polymer.

15. A method for administering drugs to a posterior region of the eye comprising placing a formulation comprising a biologically active substance comprising microspheres or microparticles with an outer diameter in the range of about 1 to 33 microns in an anterior region of the suprachoroidal space such that said microspheres or microparticles subsequently migrate to said posterior region.

16. The method according to claim 15 wherein said formulation comprises a polymer excipient to uniformly disperse the microparticles or microspheres in the suprachoroidal space.

17. A method of administering drugs in the suprachoroidal space of the eye comprising the steps of placing a needle in scleral tissues toward the suprachoroidal space at a depth of at least half of the scleral thickness, and injecting a drug formulation through said needle into the sclera such that said formulation dissects the scleral tissues adjacent to said suprachoroidal space and enters said suprachoroidal space.