Ocular therapeutic system for dispensing a medication formulation

• US 4,190,642 A
• Filed: 05/11/1979
• Issued: 02/26/1980
• Est. Priority Date: 04/17/1978
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Ben-Dor, Monique, Gale, Robert M., Keller, Nancy
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US06/038,086
• Time in Patent Office: 291 Days
• Field of Search: 424/19-22, 128/260
• US Class Current: 424/427
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants

Abstract

An ocular system is disclosed for dispensing a medication formulation to the eye. The system comprises a formulation consisting of a pilocarpine osmotic solute and an epinephrine osmotic solute dispersed in a polymer such that the formulation is surrounded substantially individually by the polymer. The system, when placed in the eye, dispenses the formulation at a controlled rate over time. A method also is disclosed for the management of intraocular pressure using the ocular system.

Claims

1. An ocular therapeutic system for dispensing a medication formulation to an eye, said system sized, shaped and adapted for easy insertion and comfortable retention in the eye and comprising, depots of a medication formulation consisting essentially of from 1 to 40 weight percent of a pilocarpine therapeutically acceptable salt of 0.1 to 100 micron size and 1 to 25 weight percent of an epinephrine therapeutically acceptable salt of 0.1 to 100 micron size, said depots dispersed in and surrounded substantially individually by a polymer that is impermeable to the passage of the medication formulation and permeable to the passage of eye fluid.

2. The ocular therapeutic system for dispensing the medication formulation according to claim 1, wherein the pilocarpine salt and the epinephrine salt are selected from the group consisting of inoganic acid addition salts, organic acid addition salts and quaternary addition salts.

3. The ocular therapeutic system for dispensing the medication formulation according to claim 1, wherein the pilocarpine therapeutically acceptable salt and the epinephrine therapeutically acceptable salt are selected from the group of salts consisting essentially of hydrochloride, nitrite, hydrobromide, hydroiodide, sulfate, sulfamate, phosphate, nitrate, acetate, bitartrate, citrate, oxalate, succinate, benzoate, tartrate, fumurate, malate, mandelate, maleate and ascorbate.

4. The ocular therapeutic system for dispensing the medication formulation according to claim 1, wherein the system is manufactured as an insert for insertion and retention in a human eye, and the depots comprise 2 to 50% by weight of the insert.

5. An ocular insert consisting essentially of (a) discrete depots of a medication formulation of a pilocarpine osmotically effective solute and an epinephrine osmotically effective solute, which solutes have a size of 0.1 to 100 microns and exhibit an osmotic pressure gradient across the wall of the depot against an external fluid present in the environment of use;

(b) a film of an ethylene-vinyl ester copolymer forming the insert, imparting size and shape to the insert for easy insertion and prolonged retention in the environment of use, said film substantially impermeable to the passage of the solutes, permeable to the passage of the external fluid and substantially surrounding individually and serving as the wall of the depots; and

, (c) wherein, when the insert is positioned in the environment of use, fluid from the environment is imbibed through the wall into the depots to continuously dissolve the solutes and generate a hydrostatic pressure in the depots which pressure is applied against the wall of the depots thereby forming apertures and releasing the formulation from the depots at the surface and from within the insert by the inward progressive aperture formation in depots at a controlled rate over a prolonged period of time.

6. The ocular insert according to claim 5, wherein the ester is the acetate, the pilocarpine solute is the nitrate, the epinephrine solute is the bitartrate, the depots house from 1 to 40 weight percent of the nitrate, and from 1 to 20 weight percent of the bitartrate, and the environment is the human eye.

7. A method for treating glaucoma in a warm-blooded animal, which method consists essentially in lowering the intraocular pressure associated with glaucoma by administering to the eye of the animal a medication formulation, the method consisting essentially in the steps of:

(a) positioning in the eye an ocular insert, said insert consisting essentially of;

(1) discrete depots of a medication formulation consisting of a pilocarpine osmotic solute and an epinephrine osmotic solute, which solutes exhibit osmotic pressure gradients across the wall of the depot against an external fluid, said depots dispersed in;

(2) a film sized and shaped as an insert for easy positioning and retention in the eye of the animal, said film a polymeric material that surrounds individually and forms the wall of the discret depots, is non-toxic, nonerodible, impermeable to the passage of the solutes and permeable to the passage of fluid;

(b) imbibing fluid from the eye into the depots to dissolve the solutes and fill the depots with solution, thereby exerting pressure aganst the wall of the depot and forming apertures that release formulation from the depots at the surface and from the interior of the insert through formulation dispensing paths made by the inward progressive aperture formation in related depots;

thereby,

(c) administering formulation to the eye at a controlled rate for treating glaucoma over a prolonged period of time.

8. The method for treating glaucoma in a warm-blooded animal according to claim 7, wherein the glaucoma is wide-angle glaucoma, the polymeric material is ethylene-vinyl acetate copolymer, and the animal is human.

9. The method for treating glaucoma in a warm-blooded animal according to claim 7, wherein the glaucoma is secondary glaucoma, the polymeric material is ethylene-vinyl acetate copolymer, and the animal is a human.

10. The method for treating glaucoma in a warm-blooded animal according to claim 7, wherein the insert administers simultaneously from 1 to 100 micrograms per hour of pilocarpine solute and from 1 to 30 micrograms per hour of epinephrine solute.

11. The method for treating glaucoma in a warm-blooded animal according to claim 7, wherein pilocarpine solute is pilocarpine nitrate and epinephrine solute is epinephrine bitartrate.