Ophthalmic drug delivery

• US 9,087,145 B2
• Filed: 07/15/2011
• Issued: 07/21/2015
• Est. Priority Date: 07/15/2010
• Status: Active Grant

• Current Assignee: Eyenovia Inc.
• Original Assignee: Eyenovia Inc.
• Inventors: Ballou, Bernard L. Jr., Packer, Mark, Inachulev, Tsontcho, Mumper, Russell John
• Primary Examiner(s): Kwon, Brian-Yong
• Assistant Examiner(s): Stevens, Mark V
• Application Number:
  US13/184,446
• Publication Number:
  US 20120070467A1
• Time in Patent Office: 1,467 Days
• US Class Current: 1/1
• CPC Class Codes: A61F 9/00 Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand caps with means for protecting the eyes A42B1/018; visors for helmets A42B3/22; retractors A61B17/02; manipulators specially adapted for use in surgery A61B34/70; appliances to aid invalids to move about A61H3/00; exercisers for the eyes A61H5/00; eye baths A61H35/02; sunglasses or goggles having the same features as spectacles G02C
• 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: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 8/06 Emulsions
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61M 2210/0612 Eyes
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: G16H 10/60 for patient-specific data, e.g. for electronic patient records
• CPC Class Codes: G16H 15/00 ICT specially adapted for medical reports, e.g. generation or transmission thereof
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 30/20 for handling medical images, e.g. DICOM, HL7 or PACS
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 40/67 for remote operation

Abstract

The present invention includes and provides a method of delivering a medicament to an eye of a subject in need thereof a solution, the method comprising: (a) providing droplets containing the medicament with a specified average size and average initial ejecting velocity; and (b) delivering the medicament to the eye, where the droplets deliver a percentage of the ejected mass of the droplets to the eye.

Claims

1. A method of delivering a medicament to an eye of a subject in need thereof as an ejected stream of droplets, the method comprising:

(a) generating the ejected stream of droplets containing said medicament via a piezoelectric actuated ejection device, said ejector device comprising;

a housing;

a reservoir disposed within the housing for receiving a volume of ophthalmic fluid;

an ejector mechanism comprising an ejector plate having a first surface coupled to a fluid delivery area of the reservoir, the ejector plate including a plurality of openings formed through its thickness; and

a piezo electric actuator coupled to a second surface of the ejector plate, the actuator being operable to oscillate the ejector plate at a frequency to thereby generate the ejected stream of droplets upon actuation;

wherein said ejected droplets have an average droplet ejecting size of between about 20 microns to about 100 microns in diameter and an average initial droplet ejecting velocity between 1 m/s and 10 m/s; and

(b) delivering said ejected stream of droplets containing said medicament to said eye of the subject in need thereof, wherein between about 85% to about 100% of the ejected mass of said droplets are deposited on the eye.

2. The method according to claim 1, wherein said medicament is delivered in an aqueous droplet solution.

3. The method according to claim 2, wherein said medicament is delivered in an oil/water emulsion droplet.

4. The method according to claim 3, wherein said oil in said oil/water emulsion droplet is a glycerin, a castor oil, or a polysorbate 80 mixture.

5. The method according to claim 1, wherein said medicament is a glaucoma medicament.

6. The method according to claim 1, wherein said medicament is an antibiotic.

7. The method according to claim 1, wherein said average droplet ejecting size is between about 30 microns to about 60 microns.

8. The method according to claim 1, wherein said average initial droplet ejecting velocity is between about 1 m/s to about 4 m/s.

9. The method according to claim 1, wherein said medicament is selected from the group consisting of ranibizumab antibody FAB, VEGF Trap fusion molecule, microplasmin enzyme, macugen pegylated polypeptide, and bevacizumab.

10. The method according to claim 1, wherein said medicament comprises a medicament selected from the group consisting of carboxymethylcellulose sodium, tetrahydrozoline HCl, pheniramine maleate, ketotifen fumarate, oxymetazoline HCl, naphazoline HCl, pheniramine maleate, moxifloxacin hydrochloride, bromfenac, proparacaine hydrochloride, difluprednate, gatifloxacin, travoprost, bepotastine besilate, gatifloxacin, loteprednol etabonate, timolol ophthalmic, olopatadine hydrochloride, phenylephrine hydrochloride, levofloxacin, ketorolac tromethamine, latanoprost, bimatoprost and BAK free latanoprost.

11. The method according to claim 1, wherein said medicament comprises a medicament selected from the group consisting of fluorosilicone acrylate, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, tetrahydrozoline HCl, carboxymethylcellulose sodium, propylene glycol, hypromellose, zinc sulfate, dorzolamide HCl timolol maleate, azithromycin, brimonidine tartrate, nepafenac, brinzolamide, besifloxacin, dorzolamide HCl, prenisone acetate, loteprednol etabonate, tobramycin/dexamethasone, and cyclosporine.

12. The method according to claim 1, wherein said medicament is selected from the group consisting of travoprost, timolol ophthalmic, latanoprost, bimatoprost, dorzolamide HCl timolol maleate, brimonidine tartrate, brinzolamide, dorzolamide HCl, and BAK free latanoprost.

34. The method of claim 1, wherein said medicament has a viscosity at 25°

C. is about 0.3 centipoise (cP) to about 300 cP.

35. The method of claim 34, wherein said viscosity is about 0.3 cP to about 30 cP.

36. The method of claim 1, wherein said medicament is isotonic with human tears or eye tissue.

37. The method of claim 1, wherein said medicament has an osmolality ranging from about 100 milli-osmoles/kilogram (mmol/kg) to about 1000 mmol/kg.

38. The method of claim 37, wherein said medicament has an osmolality ranging from about 280 mmol/kg to about 320 mmol/kg.

13. A method for providing a solution as an ejected stream of droplets to an eye of a subject in need thereof, the method comprising:

(a) generating an ejected stream of droplets of said solution via a piezoelectric actuated ejection device, the ejection device comprising;

a housing;

a reservoir disposed within the housing for receiving a volume of ophthalmic fluid;

an ejector mechanism comprising an ejector plate having a first surface coupled to a fluid delivery area of the reservoir, the ejector plate including a plurality of openings formed through its thickness; and

a piezoelectric actuator coupled to a second surface of the ejector plate, the actuator being operable to oscillate the ejector plate at a frequency to thereby generate the ejected stream of droplets upon actuation;

wherein said ejected droplets have an average droplet ejecting size of between about 20 microns to about 100 microns in diameter and an average initial droplet ejecting velocity of between about 1 m/s and 10 m/s; and

(b) delivering said ejected stream of droplets of said solution to said eye of a subject in need thereof, wherein between about 85% to about 100% of the ejected mass of said droplets are deposited on the eye.

14. The method of claim 13, wherein said solution is an isotonic saline solution.

15. The method according to claim 13, wherein said solution comprises a medicament and said medicament is delivered in an aqueous droplet solution.

16. The method according to claim 13, wherein said solution comprises a medicament and said medicament is delivered in an oil/water emulsion droplet.

17. The method according to claim 16, wherein said oil in said oil/water emulsion droplet is a glycerin, a castor oil, or a polysorbate 80 mixture.

18. The method according to claim 15, wherein said medicament is a glaucoma medicament.

19. The method according to claim 15, wherein said medicament is an antibiotic.

20. The method according to claim 13, wherein said average droplet ejecting size is between about 30 microns to about 60 microns.

21. The method according to claim 13, wherein said average droplet initial ejecting velocity is between about 1 m/s to about 4 m/s.

22. The method according to claim 15, said medicament is selected from the group consisting of ranibizumab antibody FAB, VEGF Trap fusion molecule, microplasmin enzyme, macugen pegylated polypeptide, and bevacizumab.

23. The method according to claim 15, wherein said medicament comprises a medicament selected from the group consisting of carboxymethylcellulose sodium, tetrahydrozoline HCl, pheniramine maleate, ketotifen fumarate, oxymetazoline HCl, naphazoline HCl, pheniramine maleate, moxifloxacin hydrochloride, bromfenac, proparacaine hydrochloride, difluprednate, gatifloxacin, travoprost, bepotastine besilate, gatifloxacin, loteprednol etabonate, timolol ophthalmic, olopatadine hydrochloride, phenylephrine hydrochloride, levofloxacin, ketorolac tromethamine, latanoprost, bimatoprost and BAK free latanoprost.

24. The method according to claim 15, wherein said medicament comprises a medicament selected from the group consisting of fluorosilicone acrylate, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, tetrahydrozoline HCl, carboxymethylcellulose sodium, propylene glycol, hypromellose, zinc sulfate, dorzolamide HCl timolol maleate, azithromycin, brimonidine tartrate, nepafenac, brinzolamide, besifloxacin, dorzolamide HCl, prenisone acetate, loteprednol etabonate, tobramycin/dexamethasone, and cyclosporine.

25. The method according to claim 15, wherein said medicament is selected from the group consisting of travoprost, timolol ophthalmic, latanoprost, bimatoprost, dorzolamide HCl timolol maleate, brimonidine tartrate, brinzolamide, dorzolamide HCl, and BAK free latanoprost.

26. A method of treating glaucoma in a subject in need thereof comprising:

(a) generating an ejecting stream of droplets containing a medicament for treatment of glaucoma via a piezoelectric actuated ejection device, the ejection device comprising;

a housing;

a reservoir disposed within the housing for receiving a volume of ophthalmic fluid;

an ejector mechanism comprising an ejector plate having a first surface coupled to a fluid delivery area of the reservoir, the ejector plate including a plurality of openings formed through its thickness; and

a piezoelectric actuator coupled to a second surface of the ejector plate, the actuator being operable to oscillate the ejector plate at a frequency to thereby generate the ejected stream of droplets upon actuation;

wherein said droplets have an average droplet ejecting size of between about 20 microns to about 100 microns in diameter and an average initial droplet ejecting velocity of between about 1 m/s and 10 m/s; and

(b) delivering said ejected stream of droplets containing said medicament to an eye of said subject in need thereof, wherein between about 85% to about 100% of the ejected mass of said droplets are deposited on the eye.

27. The method according to claim 26, wherein said medicament is delivered in an aqueous droplet solution.

28. The method according to claim 27, wherein said medicament is delivered in an oil/water emulsion droplet.

29. The method according to claim 28, wherein said oil in said oil/water emulsion droplet is a glycerin, a castor oil, or a polysorbate 80 mixture.

30. The method according to claim 26, wherein said average droplets ejecting size is between about 30 microns to about 60 microns.

31. The method according to claim 26, wherein said average droplet initial ejecting velocity is between about 1 m/s to about 4 m/s.

32. The method according to claim 26, said medicament is selected from the group consisting of travoprost, timolol ophthalmic, latanoprost, bimatoprost, dorzolamide HCl timolol maleate, brimonidine tartrate, brinzolamide, dorzolamide HCl, and BAK free latanoprost.

33. A method of providing a reduced dosage of a medicament to an eye of a subject in need thereof as an ejected stream of droplets, the method comprising:

(a) generating an ejected stream of droplets containing said medicament via a piezoelectric actuated ejection device, the ejection device comprising;

a housing;

a reservoir disposed within the housing for receiving a volume of ophthalmic fluid;

an ejector mechanism comprising an ejector plate having a first surface coupled to a fluid delivery area of the reservoir, the ejector plate including a plurality of openings formed through its thickness; and

a piezoelectric actuator coupled to a second surface of the ejector plate, the actuator being operable to oscillate the ejector plate at a frequency to thereby generate the ejected stream of droplets upon actuation;

wherein said droplets have an average ejecting droplet size of between about 20 microns and about 100 microns in diameter and an average initial droplet ejecting velocity of between 1 m/s and 10 m/s; and

(b) delivering said ejected stream of droplets containing said medicament to said eye of said subject in need thereof, wherein between about 85% to about 100% of the ejected mass of said droplets are deposited on the eye, and wherein said droplets provide a total volume of less than 30 μ

l to said eye.