Anterior Segment Drug Delivery

• US 20120136322A1
• Filed: 06/01/2011
• Published: 05/31/2012
• Est. Priority Date: 06/03/2009
• Status: Active Grant

• Current Assignee: ForSight VISION5, Inc. (Abbvie Incorporated)
• Original Assignee: Forsight Labs, LLC
• Inventors: Alster, Yair, de Juan, Eugene Jr., Reich, Cary J., Boyd, Stephen, Sierra, David, Alejandro, Jose D., Sutton, Douglas, Macfarlane, K. Angela
• Granted Patent: US 9,421,126 B2
• Time in Patent Office: Days
• US Class Current: 604/290
• CPC Class Codes: A61F 2230/0006 circular
• 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: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/43 Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula , e.g. penicillins, penems
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61M 31/002 : Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61P 27/02 : Ophthalmic agents

Abstract

A therapeutic system comprises an ocular insert placed on a region outside an optical zone of an eye. The ocular insert comprises two structures: a first skeletal structure and a second cushioning structure. The first structure functions as a skeletal frame which maintains positioning of the implant along the anterior portion of the eye and provides support to the second, cushioning structure. This first structure maintains the attachment of the therapeutic system to the anterior portion of the eye for at least thirty days. In some embodiments the first structure remains a constant size and shape, e.g. a ring shape, a ring with haptics, or a curvilinear ring that is confined to and restrainingly engages the inferior and superior conjunctival fornices so as to retain the implant within the tear fluid and/or against the tissues of the eye.

Claims

1. A non-corneal therapeutic system located outside of an optical zone of an eye capable of sustained release of one or more drugs to the eye for at least 30 days comprising:

a first skeletal structure to attach, provide support, and maintain attachment of the therapeutic system of an anterior portion of the eye, and

a second structure, at least partially disposed along a length of the first structure, to provide cushioning to and a means of delivering at least one drug to the eye on at least one of the two structures.

2. An ocular insert for use in an eye, the eye having upper and lower lids extendable along an anterior eye surface with an optical zone therebetween, the insert comprising:

a first structure disposable along the anterior surface of the eye of a patient outside the optical zone;

a second structure supported by the first structure, the second structure cushioning engagement between the insert and the eye so as to inhibit irritation of the eye when the first structure helps maintain the insert in contact with the eye for a plurality of days; and

at least one drug supported by the first structure so as release a safe and therapeutically effective quantity of the drug to the eye for each of the plurality of days.

3. The ocular insert of claim 2, wherein the insert has an annular expulsion-inhibiting shape with a posterior surface for engagement with the anterior surface of the eye, an anterior surface, and radially inner and outer edges extending therebetween, the first structure extending along a circumference of the annular shape so as to maintain the shape of the annulus sufficiently to capture the insert between the upper lid and the anterior surface of the eye, and between the lower lid and the anterior surface of the eye, the second structure disposed between the first structure and an eye tissue, the eye tissue comprising the sclera and/or at least one of the lids.

4. The ocular insert of claim 3, wherein the drug is disposed on or in the first structure.

5. The ocular insert of claim 3, wherein the drug is disposed on or in the second structure.

6. The ocular insert of claim 2, wherein the plurality of days comprises at least 30 days.

7. The ocular insert of claim 2, wherein the drug comprises one or more member selected from the group consisting of:

steroids, anti-inflammatories, antibiotics, glaucoma treatment compounds, antihistamines, and/or dry eye medication.

8. The ocular insert of claim 2, wherein the drug comprises one or more member selected from the group consisting of:

a steroid, including glucocorticoids, aprogestins, amineralocorticoids, corticosteroids, corticosteroids include cortisone, hydrocortisone, prednisone, prednisolone, methylprednisone, triamcinolone, fluoromethalone, dexamethasone, medrysone, betamethasone, loteprednol, fluocinolone, flumethasone, rimexolone mometasone, androgens, testosterone, methyltestosterone, and/or danazol;

an NSAID including piroxicam, aspirin, salsalate (Amigesic), diflunisal (Dolobid), ibuprofen (Motrin), ketoprofen (Orudis), nabumetone (Relafen), piroxicam (Feldene), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), indomethacin (Indocin), sulindac (Clinoril), tolmetin (Tolectin), etodolac (Lodine), ketorolac (Toradol), oxaprozin (Daypro), and/or celecoxib (Celebrex);

an antibiotic including amoxicillin, penicillin, sulfa drugs, erythromycin, streptomycin, tetracycline, clarithromycin, terconazole, azithromycin, bacitracin, ciprofloxacin, evofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, aminoglycosides, tobramycin, gentamicin, polymyxin B combinations, polymyxin B/trimethoprim, polymyxin B/bacitracin, and/or polymyxin B/neomycin/ gramicidin;

a glaucoma treatment medication including beta-blockers, timolol, betaxolol, levobetaxolol, carteolol, miotics, pilocarpine;

carbonic anhydrase inhibitors, brinzolamide, dorzolamide;

prostaglandins, travoprost, bimatoprost, latanoprost;

seretonergics;

muscarinics;

dopaminergic agonists;

adrenergic agonists, apraclonidine, brimonidine, prostaglandins, prostaglandin analogs, latanoprost, bimatoprost, and/or travoprost;

antihistamines and mast cell stabilizers including Olopatadine and epinastine, acute care anti-allergenic products, ketorolac tromethamine, ketotifen fumarate, loteprednol, epinastine HCl, emedastine difumarate, azelastine hydrochloride, Olopatadine hydrochloride, ketotifen fumarate;

chronic care anti-allergenic products, pemirolast potassium, nedocromil sodium, lodoxamide tromethamine, cromolyn sodium; and

/or p1 dry eye medication including cyclosporine.

9. The ocular insert of claim 2, wherein the drug is hydrophilic, and wherein the drug is dispersed in a hydrophilic polymer.

10. The ocular insert of claim 2, wherein the drug is hydrophobic, and wherein the insert comprises surfactants to increase the drub solubility.

11. The ocular insert of claim 2, wherein the drug is hydrophobic, and wherein the insert comprises an elution rate decrease material, the elution rate decrease material comprising a coating over the drug, a component of a delivery matrix and/or a coating on the delivery matrix.

12. The ocular insert of claim 2, wherein the first structure comprise an annulus with two radial protrusions extending radially outwardly from the annulus so as to engage the lids and position the insert around the optical zone when the eye blinks.

13. The ocular insert of claim 2, wherein the first structure comprises an annulus with a local thickening along at least one portion of the annulus.

14. The ocular insert of claim 2, wherein the first structure comprises an annulus and a plurality of haptics extending radially from the annulus.

15. The ocular insert of claim 2, wherein the first structure comprises an annulus, at least one arc radially offset from the annulus, and a plurality of radial members extending between the at least one arc and annulus.

16. The ocular insert of claim 2, wherein the first structure comprises a serpentine annulus having radially inward portions interspersed with radially outward portions.

17. The ocular insert of claim 2, wherein the first structure comprises an annulus having inner and outer edges, at least one of the edges being atraumatically shaped to avoid sharp-edge irritation of the eye.

18. The ocular insert of claim 2, wherein the first structure comprises an annulus having a non-planar eye-engagement surface.

19. The ocular insert of claim 2, wherein the first structure comprises an annulus, wherein the second structure swells when hydrated, and further comprising a separated series of swell-inhibiting bands disposed over the first and second structures.

20. The ocular insert of claim 2, further comprising a configuration altering material coupled with the first structure so as to provide an insertion shape prior to deployment, the deployment of the insert in the eye altering the configuration altering material so that the insert assumes a deployed shape in the eye, the insertion shape having greater pushability than the deployed shape.

21. The ocular insert of claim 2, further comprising an actuatable delivery instrument having a receptacle for releasably receiving the insert so as to support the insert during positioning of the insert, wherein actuation of the delivery instrument when at least a portion of the insert engages the eye between a sclera and a lid atraumatically releases the insert from the receptacle.

22. An ocular insert system for treating an eye, the eye having upper and lower lids extendable along an anterior eye surface with an optical zone therebetween, the system comprising:

an insert engageable against the anterior surface of the eye under at least one of the lids;

a re-configuration material or tool coupled to the insert so as to configure the insert in an insertion configuration, wherein activation of the material or tool reconfigures the insert to deployed configuration comprising an annulus disposable outside the optical zone between the anterior surface of the eye and the lids; and

at least one drug supported by the annulus so as release a safe and therapeutically effective quantity of the drug to the eye for each of the plurality of days when deployed therein.

23. A method of treating an eye, the method comprising:

placing a first skeletal structure on an anterior portion of the eye outside of an optical zone of the eye, wherein a second structure is at least partially disposed along a length of the first structure so as to provide cushioning to and to deliver at least one drug to the eye on at least one of the two structures.