Anterior segment drug delivery

• US 10,004,636 B2
• Filed: 08/05/2016
• Issued: 06/26/2018
• Est. Priority Date: 06/03/2009
• Status: Active Grant

• Current Assignee: ForSight VISION5, Inc. (Abbvie Incorporated)
• Original Assignee: ForSight VISION5, Inc. (Abbvie Incorporated)
• Inventors: Alster, Yair, de Juan, Jr., Eugene, Reich, Cary J., Boyd, Stephen, Sierra, David, Alejandro, Jose D., Macfarlane, K. Angela, Sutton, Douglas
• Primary Examiner(s): Barham, Bethany P
• Assistant Examiner(s): Lazaro, Dominic
• Application Number:
  US15/230,275
• Publication Number:
  US 20170056242A1
• Time in Patent Office: 690 Days
• Field of Search: None
• 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. 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 comprising an annulus formed of a non-biodegradable suture having a length disposable along the anterior surface of the eye of a patient sized to fit outside the optical zone of the cornea;

a second structure completely surrounding the suture such that at least a portion of the length of the suture threads through an interior of the second 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 disposed on or embedded into the second structure so as to release a safe and therapeutically effective quantity of the drug to the eye for each of the plurality of days.

2. The ocular insert of claim 1, wherein the at least one drug is further disposed on or in the first structure.

3. The ocular insert of claim 1, wherein the at least one drug is releasable from the second structure for at least 30 days.

4. The ocular insert of claim 1, wherein the at least one drug is hydrophilic, and wherein the second structure is a hydrophilic polymer.

5. The ocular insert of claim 1, wherein the at least one drug is hydrophobic, and wherein the insert comprises surfactants to increase the drug solubility.

6. The ocular insert of claim 1, wherein the at least one drug is hydrophobic, and wherein the insert comprises an elution rate decrease material, the elution rate decrease material comprising a coating over the second structure or a component of a delivery matrix forming the second structure.

7. The ocular insert of claim 1, wherein the first structure further comprises 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.

8. The ocular insert of claim 1, wherein the first structure further comprises a local thickening along at least one portion of the annulus.

9. The ocular insert of claim 1, wherein the first structure further comprises a plurality of haptics extending radially from the annulus.

10. The ocular insert of claim 1, wherein the first structure further comprises at least one arc radially offset from the annulus, and a plurality of radial members extending between the at least one arc and annulus.

11. The ocular insert of claim 1, wherein the annulus of the first structure comprises a serpentine annulus having radially inward portions interspersed with radially outward portions.

12. The ocular insert of claim 1, wherein the annulus of the first structure has inner and outer edges, at least one of the edges being atraumatically shaped to avoid sharp-edge irritation of the eye.

13. The ocular insert of claim 1, wherein the annulus of the first structure has a non-planar eye-engagement surface.

14. The ocular insert of claim 1, wherein the second structure swells when hydrated, and the insert further comprises a separated series of swell-inhibiting bands disposed over the first and second structures.

15. The ocular insert of claim 1, wherein the at least one drug comprises one or more members selected from the group consisting of:

a steroid selected from the group consisting of at least one of glucocorticoids, aprogestins, amineralocorticoids, corticosteroids, cortisone, hydrocortisone, prednisone, prednisolone, methylprednisone, triamcinolone, fluoromethalone, dexamethasone, medrysone, betamethasone, loteprednol, fluocinolone, flumethasone, rimexolone mometasone, androgens, testosterone, methyltestosterone, and danazol;

a non-steroidal anti-inflammatory (NSAID) selected from the group consisting of at least one of piroxicam, aspirin, salsalate, diflunisal, ibuprofen, ketoprofen, nabumetone, piroxicam, naproxen, diclofenac, indomethacin, sulindac, tolmetin, etodolac, ketorolac, oxaprozin, and celecoxib;

an antibiotic selected from the group consisting of at least one of amoxicillin, penicillin, sulfa drugs, erythromycin, streptomycin, tetracycline, clarithromycin, terconazole, azithromycin, bacitracin, ciprofloxacin, evofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, aminoglycosides, tobramycin, gentamicin, and polymyxin B combinations, wherein the polymyxin B combinations are selected from the group consisting of polymyxin B/trimethoprim, polymyxin B/bacitracin, and polymyxin B/neomycin/gramicidin;

a glaucoma treatment medication selected from the group consisting of at least one of beta-blockers, mitotics, carbonic anhydrase inhibitors, prostaglandins, prostaglandin analogs, seretonergics, muscarinics, dopaminergic agonists, and adrenergic agonists,

wherein the beta-blockers are selected from the group consisting of timolol, betaxolol, levobetaxolol, and carteolol,

wherein the mitotics are selected from the group consisting of pilocarpine,

wherein the carbonic anhydrase inhibitors are selected from the group consisting of brinzolamide, and dorzolamide,

wherein the prostaglandin analogs are selected from the group consisting of travoprost, bimatoprost, and latanoprost, and

wherein the adrenergic agonists are selected from the group consisting of apraclonidine, and brimonidine;

an antihistamine and mast cell stabilizer selected from the group consisting of at least one of ketorolac tromethamine, ketotifen fumarate, loteprednol, epinastine HCl, emedastine difumarate, azelastine hydrochloride, olopatadine hydrochloride;

a chronic care anti-allergenic product selected from the group consisting of at least one of pemirolast potassium, nedocromil sodium, lodoxamide tromethamine, and cromolyn sodium; and

a dry eye medication selected from the group consisting of cyclosporine; and

an anesthetic.

16. The ocular insert of claim 1, wherein the second structure has a cross-sectional shape that is rounded or beveled.

17. The ocular insert of claim 1, wherein the first structure is a polypropylene suture or a nylon suture.

18. The ocular insert of claim 17, wherein the second structure is a silicone matrix.

19. The ocular insert of claim 18, wherein the second structure comprises a plurality of cushioning structures, each cushioning structure completely surrounding a discrete portion of the length of the suture.