Topical Ocular Delivery Methods and Devices for Use in the Same

• US 20190314195A1
• Filed: 06/18/2019
• Published: 10/17/2019
• Est. Priority Date: 04/12/2018
• Status: Active Application

• Current Assignee: Bausch + Lomb Ireland Ltd. (Bausch Health Cos., Inc.)
• Original Assignee: Kedalion Therapeutics, Inc. (Novartis Ag)
• Inventors: Ivri, Ehud, Blumenkranz, Mark, Noymer, Peter
• Application Number:
  US16/444,894
• Publication Number:
  US 20190314195A1
• Time in Patent Office: Days
• CPC Class Codes: A61F 9/0008 Introducing ophthalmic products into the ocular cavity or retaining products therein putting in contact lenses A61F9/0061; introducing or retaining media in cavities of the body in general A61M31/00
• CPC Class Codes: A61F 9/0026 Ophthalmic product dispenser attachments to facilitate positioning near the eye
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/472 Non-condensed isoquinolines, e.g. papaverine
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

Methods of administering a liquid formulation of an ophthalmic agent to a topical ocular location of an eye are provided. Aspects of the methods include delivering to the topical ocular location a dose of the liquid formulation that can be wholly accommodated by the tear film of the eye. Devices and kits for practicing the methods are also provided. The methods, compositions and kits find use in a variety of applications, including therapeutic, diagnostic and cosmetic applications.

Claims

1. A method of treating a subject for presbyopia, the method comprising:

administering to a topical ocular location of the subject a micro-dose of a precise, known mass of a cholinergic agent effective to treat the subject for presbyopia,

wherein the micro-dose is administered by a handheld device that comprises;

a container comprising a liquid formulation of the miotic agent and a single aperture; and

an actuator configured to emit the micro-dose from the container through the single aperture.

2. The method according to claim 1, wherein the micro-dose has a volume ranging from 1 to 15 μ

l.

3. The method according to claim 2, wherein the micro-dose has a volume ranging from 3 to 10 μ

l.

4. The method according to claim 1, wherein the cholinergic agent is a miotic agent.

5. The method according to claim 3, wherein the miotic agent is selected from the group consisting of:

pilocarpine, carbochol, physostigmine, echothiophate, methacholine, moxisylyte and pharmaceutically acceptable salts thereof, and combinations thereof.

6. The method according to claim 5, where the miotic agent is pilocarpine.

7. The method according to claim 1, wherein the micro-dose does not include any agent that ameliorates an adverse effect of the cholinergic agent.

8. The method according to claim 7, wherein the cholinergic agent is the sole active agent in the micro-dose.

9. The method according to claim 1, wherein the precise, known mass of cholinergic agent delivered to the topical ocular location has a mass equal to the administered volume times the concentration of miotic agent in the liquid formulation of the micro-dose.

10. The method according to claim 9, wherein the precise, known mass of cholinergic agent delivered to the topical ocular location is determined from pulse duration and active agent concentration in the liquid formulation.

11. The method according to claim 1, wherein the method results in a reduction in pupil diameter ranging from 0.25 to 10 mm as compared with prior to drug administration.

12. The method according to claim 1, wherein the method results in improvement in visual acuity ranging from 2 to 6 lines on a Jaeger or Rosenbaum near card or ETDRS Near Chart.

13. The method according to claim 1, wherein the micro-dose is administered as a collimated stream of the liquid formulation.

14. The method according to claim 13, wherein the collimated stream is continuous.

15. The method according to claim 13, wherein the collimated stream is discontinuous.

16. The method according to claim 1, wherein the micro-dose is administered as a series of streams.

17. The method according to claim 1, wherein the micro-dose is administered as a plurality of droplets.

18. The method according to claim 1, wherein the micro-dose is self-administered.

19. The method according to claim 1, wherein the container comprises a volume of the liquid formulation sufficient to provide multiple micro-doses.

20. The method according to claim 1, wherein the liquid formulation is preservative-free.

21. The method according to claim 1, wherein the device comprises an image-based alignment system configured to enable self-alignment by the user of the aperture with the target location.

22. The method according to claim 21, wherein the subject employs the image-based alignment system to align the aperture with the target location.