Bioadhesive ophthalmic insert

• US 5,773,021 A
• Filed: 11/18/1996
• Issued: 06/30/1998
• Est. Priority Date: 03/14/1994
• Status: Expired due to Term

• Current Assignee: Vetoquinol USA, Inc. (Neogen Corporation)
• Original Assignee: Vetoquinol USA, Inc. (Neogen Corporation)
• Inventors: Gurtler, Florian, Gurny, Robert
• Primary Examiner(s): PEZZUTO, HELEN LEE
• Application Number:
  US08/751,561
• Time in Patent Office: 589 Days
• Field of Search: 424/427
• US Class Current: 424/427
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants

Abstract

A bioadhesive ophthalmic insert is described which is intended more particularly for the prolonged and controlled release of a medicinal substance. The insert comprises a composite polymeric material matrix in which the medicinal substance is incorporated.

The composite polymeric material matrix comprises a water-soluble biocompatible polymer and a bioadhesive biocompatible polymer and, where applicable, a water-insoluble biocompatible polymer.

Claims

1. An ophthalmic insert useful for the prolonged and controlled release of at least one medicinal substance, which comprises a homogeneous mixture of a composite polymeric material matrix and the medicinal substance, said composite polymeric material matrix comprising a mixture of:

a water-soluble biocompatible polymer selected from hydroxyalkyl celluloses, maltodextrins, chitosans, modified starches or polyvinyl alcohols,

a water-insoluble biocompatible polymer selected from alkylcelluloses, and

a bioadhesive biocompatible polymer selected from polyvinyl carboxylic acids or sodium carboxymethyl celluloses,

said insert being prepared by extrusion, thermoforming or heat compression of said homogeneous mixture.

2. An ophthalmic insert according to claim 1, wherein the composite polymeric material matrix comprises from 50 to 99.5% by weight of the water-soluble biocompatible polymer and from 0.5 to 5% by weight of the bioadhesive biocompatible polymer, any remainder up to 100% by weight being the water-insoluble biocompatible polymer.

3. An ophthalmic insert according to claim 1, wherein the hydroxyalkyl cellulose is a hydroxypropyl cellulose having a molecular weight of between 10,000 and 1,000,000.

4. An ophthalmic insert according to claim 1, which comprises 0.5 to 50% by weight of the medicinal substance.

5. An ophthalmic insert according to claim 1, wherein the medicinal substance is selected from the group consisting of antibacterial, antiviral, antimycotic, anti-glaucoma, antiphlogistic, anti-inflamatory, anti-allergy, vasoconstrictive, vaso-dilatory, myotic, mydriatic, anaesthetic and lubricant agents.

6. An ophthalmic insert according to claim 1, wherein the medicinal substance is in the form of an inclusion product in a support, an adsorption product on a support or a co-precipitation product with a support, said support being a pharmaceutically acceptable product which is at least one of water-soluble, biodegradable, and able to lose its physical cohesion when brought into contact with a biological fluid.

7. An ophthalmic insert according to claim 1, wherein the medicinal substance is in the form of a solid solution with a pharamaceutically acceptable product which is at least one of water-soluble, biodegradable, and able to lose its physical cohesion when brought into contact with a biological fluid.

8. An ophthalmic insert according to claim 7, wherein said pharmaceutically acceptable product is selected from the group consisting of acrylic acid polymers;

methacrylic acid copolymers;

carboxylic acid esters of cellulose or cellulose derivatives;

polymers of vinyl esters of carboxylic acids;

carboxylic acid esters of starch; and

their mixtures.

9. An ophthalmic insert according to claim 1, wherein the bioadhesive biocompatible polymer is a non-neutralized polyvinyl carboxylic acid having a molecular weight of between 450,000 and 4,000,000.

10. A process for manufacturing an ophthalmic insert useful for the prolonged and controlled release of at least one medicinal substance, which comprises a matrix of a composite polymeric material in which the medicinal substance is incorporated, comprising forming a homogeneous mixture of:

a water-soluble biocompatible polymer selected from hydroxyalkyl celluloses, maltodextrins, chitosans, modified starches or polyvinyl alcohols,

a water-insoluble biocompatible polymer selected from alkylcelluloses,

a bioadhesive biocompatible polymer selected from polyvinyl carboxylic acids or sodium carboxymethyl celluloses, and

a medicinal substance,

and extruding, thermoforming or heat compressing said polymeric mixture.

11. A product produced by the process of claim 10.