Ocular treatment

• US 4,952,212 A
• Filed: 01/23/1989
• Issued: 08/28/1990
• Est. Priority Date: 11/13/1985
• Status: Expired due to Term

• Current Assignee: Imperial Chemical Industries PLC (Nouryon BV)
• Original Assignee: Imperial Chemical Industries PLC (Nouryon BV)
• Inventors: Rowe, Raymond C., Booth, Christopher G.
• Primary Examiner(s): Pellegrino, Stephen C.
• Assistant Examiner(s): Rafa, Michael
• Application Number:
  US07/299,689
• Time in Patent Office: 582 Days
• Field of Search: 604/20, 604/21, 604/289, 604/290, 604/294-298
• US Class Current: 604/294
• 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: B05B 5/025 Discharge apparatus, e.g. electrostatic spray guns
• CPC Class Codes: B05B 5/1691 Apparatus to be carried on or by a person or with a container fixed to the discharge device

Abstract

A method of administering less than 20 μl of a solution of an ophthalmically effective substance to the eye characterized in that the formulation has a viscosity and resistivity which makes it suitable for electrodynamic spraying, and the formulation is supplied to a spray nozzle wherein a sufficiently large electrical potential, relative to earth, is applied to the formulation that a sufficient electrical gradient is provided at the spray nozzle to atomize the formulation as a spray of electrically charged droplets. Also liquid solution formulations of ophthalmically effective substances for use in the method of the invention; and electrodynamic spraying apparatus, convenient for hand held use, for use in the method of the invention.

Claims

1. An improved method of administering an ophthalmically active formulation to the corneal surface of an eye, said improvement essentially comprising the steps of:

providing a nozzle having an outlet adjacent an electrode, which electrode is spaced from said outlet and electrically insulated from said nozzle;

providing as said formulation a liquid mixture comprised of an ophthalmically active substance and an ophthalmically acceptable diluent;

placing said nozzle outlet and adjacent electrode in proximity to, but spaced from, said corneal surface;

causing a measured unit dose of up to 20 μ

l of said formulation to flow from said nozzle outlet simultaneously with applying to said formulation an electrical potential by means of a high voltage generator while maintaining said electrode at relative ground potential, said electrical potential being sufficiently large to atomize said formulation leaving said nozzle outlet into a spray of electrically charged droplets;

whereupon said electrically charged droplets of said formulation are drawn to said corneal surface and uniformly deposited thereover.

2. The method of claim 1 wherein said formulation is comprised of an ophthalmically active substance and an ophthalmically acceptable diluent which comprises 50% to 100% by weight of an ophthalmically acceptable diluent and from 0% to 50% by weight of water, and has a viscosity in a range of 10^-3 to 1.0 Pa.s at 25°

C. and a resistivity in the range of 10⁴ to 10¹² ohm.cm at 25°

C.

3. The method of claim 2 in which the ophthalmically active substance is selected from the group consisting of a chemotherapeutical agent, a compound to aid ocular examination and a compound to aid surgery.

4. The method of claim 3 wherein the ophthalmically active substance is selected from the group consisting of:

(a) anti-inflammatory agents, such as prednisolone and other corticosteroids;

(b) antimicrobial drugs, such as antibiotics, antiseptics, antivirals, fungicides and sulphonamides, for example chloramphenicol, sulphacetamide, gentamycin, nystatin, acyclovir and idoxuridine;

(c) autonomic drugs, such as β

-adrenoceptor antagonists, cycloplegics, miotics, mydriatics and vasoconstrictors, for example timolol, atenolol, pilocarpine, atropine, tropicamide, hyoscine, ephedrine, phenylephrine, carbachol, guanethidine and adrenaline;

(d) local anaesthetics, such as lignocaine or oxybuprocaine;

(e) diagnostics, such as fluorescein;

(f) drugs to assist healing of corneal abrasions, such as urogastrone and epidermal growth factor (EGF); and

(g) drugs of use in diabetic retinopathy, such as aldose reductase inhibitors, for example sorbinil and 3-(4-bromo-2-fluorobenzyl)-4-oxo-3H-phthalazin-1-ylacetic acid.

5. The method of claim 4 in which the amount of water present in said formulation is from 0% to 20% by weight of the total diluent.

6. The method of claim 2 wherein the ophthalmically active organic diluent is selected from the group consisting of dimethylisosorbide, glycerol, propylene glycol, polyethylene glycol of average molecular weight up to 600, maize oil and arachis oil, optionally in combination with polyethoxyethylated castor oils, polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene sorbitan derivatives, polyoxyethylene oleyl ethers, castor oil and olive oil.

7. The method of claim 1 wherein the nozzle is charged with a unit dose of the formulation from an external source for each use.

8. The method of claim 1 wherein a unit dose of the formulation is supplied to the nozzle automatically from a reservoir.

9. The method of claim 1 wherein a single measured unit dose of said formulation is provided together with said nozzle which nozzle is replaceable.

10. The method of claim 1 wherein the measured unit dose of said formulation is provided to said nozzle by drawing into the nozzle the required amount of said formulation from an external source by means of pipette action.