WO2001049334A1

WO2001049334A1 - Intracorneal implant, and a method of treating cornea deformities

Info

Publication number: WO2001049334A1
Application number: PCT/BR2001/000002
Authority: WO
Inventors: Paulo Ferrara De Almeida Cunha
Original assignee: FERRARA OPHTHALMICS LTDA
Current assignee: FERRARA OPHTHALMICS LTDA
Priority date: 2000-01-06
Filing date: 2001-01-05
Publication date: 2001-07-12
Anticipated expiration: 2002-07-06
Also published as: AU2131301A; BR0000016A

Abstract

The present invention relates to an intracorneal implant device comprising a solid or gelatinous body constituted by a biocompatible polymer having at least one outer surface and a material reactive to the biocompatible polymer and covalently bonded to the implant device body being applied to said outer surface as a coating, said reactive material having chemical characteristics similar to those of the fundamental substance of the cornea.

Description

INTRACO NEAL IMPLANT , AND A METHOD OF TREATING CORNEA DEFORMITIES

Field of the Invention

The present invention relates to a device for corneal implant adapted to be implanted within the region of the stroma with the purpose of altering the corneal shape. The present implant device is particularly suitable for the treatment of cornea deformities such as keratoconus, irregular astigmatisms due to cornea transplant and after Lasik and PRK refractive corneal surgeries, myopia and other ametropias. Background of the Invention Intrastromal implant devices are used in eye surgical procedures to repair deformities of the cornea and their primary function is to modify the cornea curvature. Brazilian Patent PI 8705060 discloses a ring for implant in the cornea which comprises a solid or gelatinous polymeric body having a diameter that varies from the diameter of the cornea and an equally variable thickness, and is suitable for correcting myopia and other ametropias.

Document US 5,653,752 discloses a device for intrastromal corneal implant containing at least one portion adapted to be placed in the cornea so as to change the refractive properties of the eye and which comprises a flexible ring consisting of a plurality of coils. The thickness of the portion to be placed into the eye will depend upon the number of scoils inserted in the ring.

Another ring already known from the prior art as an intrastromal corneal implant is described in document US 5,888,243. The ring defined therein comprises at least one outer layer of a physiologically compatible polymer having low modulus of elasticity and that may be hydratable and hydrophilic, and an inner layer formed by a polymer presenting high modulus of elasticity. Polymers suitable for the inner layer may be selected from methyl methacrylate polymers, TEFLON, certain long-chained silicones, polycarbonates, polyolefins, elastomer polymers, among others. On the other hand, polymers having low modulus of elasticity include biological polymers such as cross-linked dextran, cross-linked heparin and hyaluronic acid. Still according to that document, said rings may be lubricated while they are introduced into the eye, and suitable lubricants may be chosen from the group consisting of hyaluronic acid, methyl ethyl cellulose, dextran solutions, glycerine solutions, polysaccharides or oligosaccharides, these compounds being used exclusively as lubricants.

Although implant devices known from the prior art present good results, it was still desirable to develop an implant material that could provide specially better biocompatibility characteristics. Summary of the Invention

The present invention refers to a device for intracomeal implant, which comprises a solid or gelatinous body constituted by a biocompatible polymer having at least one outer surface, wherein said outer surface is coated with a material which is reactive to the biocompatible polymer and which is covalently linked to the body of the implant device, said reactive material having chemical characteristics that are similar to those of the fundamental substance of the cornea.

The invention further relates to a method of treating deformities of the cornea, which comprises the steps of providing a cavity in the corneal stroma and introducing into said cavity a device as defined above. Detailed Description of the Invention

It has now been found that corneal implant devices produced from biocompatible polymers can present improved results when they include a coating applied to its outer surface consisting of a material that is reactive to said polymer and that has chemical characteristics similar to those of the fundamental substance of the cornea.

The term "coating" as used herein is intended to define the formation of a layer of the reactive material on the outer surface of the implant device by means of covalent chemical reactions between said reactive material and the polymer that constitutes the body of the implant. The so formed covalent bonds provides anchorage points between the layer of reactive material and the body of the implant. Since it is composed by a substance that has chemical characteristics similar to those of the corneal tissue, the coated outer layer of the implant device according to the present invention becomes inert with respect to the corneal tissue, and therefore it does not stimulate possible immune responses after the device has been implanted into the eye. In this way, when the device as a whole is implanted into the eye, it becomes an integral part of the corneal tissue itself, thus becoming immunologically inert and reducing any possibility of rejection.

The implant device of the present invention has a solid or gelatinous body that may be produced from biocompatible polymers conventionally used for this purpose. In a particularly preferred way, methacrylate polymers, such as polymethylmethacrylate (PMMA) are used.

The reactive material coated on the biocompatible polymer body is preferably selected from the group consisting of chemical compounds containing carboxyl groups available for reacting with said polymer and to form covalent chemical bonds with same. Among those chemical compounds, mucopolysaccharides, proteins, chondroitin sulfates and cheratan-sulfates may be used. More preferably, the compound used is hyaluronic acid or chondroitin sulfates, which comprise, for example, B-D-glycuronic acid and N-acethyl-B-D-galactosamine-sulfate copolymers, B-D-iduronic acid and N-acethyl-B-D-galactosamine-sulfate copolymers and B-D- glycuronic acid and B-D-N-acethyl-B-D-galactosamine-sulfate copolymers.

When PMMA is used as the polymeric body of the implant device of the invention, the steps of carrying out chemical reaction between PMMA and the coating material may be illustrated by the schema given below. The PMMA is first subjected to hydrolysis and is subsequently reacted with the chosen reactive material (in the case illustrated below, chondroitin sulfate acid is used).

The final shape and size of the corneal implant device according to the present invention will depend upon the purposes and desired results, that is to say, the specific corneal deformities to be corrected. In the same way, the amount and, consequently, the thickness of the reactive coating layer applied on the implant polymeric body are not a limiting parameter of the invention since they can be determined according to each specific case. It was found, however, that advantageous results can be achieved with a coating layer having thickness of 1 TA wherein the coating may cover the whole implant outer surface or only some areas that will effectively be in contact with the corneal tissue.

According to particularly preferred embodiments of the invention, the implant device has the configuration of a ring such as the one defined in Brazilian Patent PI 8705060 or the one disclosed in Pat. US 5,792,161 , and it may have the shape of a spherical cap with transverse through orifice, or the structure of several concentric rings of different diameters connected to each other.

The implant device presented now provides excellent results of biocompatibility when used in surgical methods of correcting cornea deformities such as keratoconus, irregular astigmatisms due to cornea transplant and after Lasik and PRK refractive cornea surgeries, myopia and other ametropias. This kind of method comprises the steps of forming a cavity in the corneal stroma, preferably in the form of a tunnel, and introducing in said cavity an implant device as defined above. Said cavities may be produced by conventional surgical procedures according to the desired refractive correction.

The illustrative example presented below will describe the present invention in a better way. However, the parameters and procedures illustrated therein relate merely to some embodiments of the present invention and should not be understood as limiting the scope of the invention. Example Preparation of PMMA rings coated with chondroitin sulfate

PMMA rings in solid state were treated with a 25% solution of hyragin hydrate in 50% methanol saturated with CO2 for about 4 - 5 hours at 50° C.

After the reaction was completed, the mixture was semi-filtered and the rings were washed with a solution of 50% methanol.

Then, an aqueous solution containing chondroitin sulfate was added to the rings together with an aqueous solution 1.5% of 1-cyclohexyl-3-(2-ufolionethyl) carbodiimida met-p-toluenosulfate, pH 4.7. The mixture was stirred for 8 hours at 4°

C. The solution was then filtered, and the coated rings were washed with an 0.85%

NaCI solution.

Claims

1. An intracomeal implant device comprising a solid or gelatinous body made of a biocompatible polymer and having at least an outer surface, wherein a substance reactive to the biocompatible polymer is applied to said outer surface and is bonded to the polymeric body of the implant device by chemical covalent bonds, said reactive substance having chemical characteristics similar to those of the corneal fundamental substance.

2. An implant device according to claim 1 , wherein the biocompatible polymer is a methylmethacrylate polymer.

3. An implant device according to claim 1 or 2, wherein the substance reactive to the biocompatible polymer is selected from the group consisting of chemical compounds that contain carboxyl groups.

4. A device according to claim 3, wherein the substance reactive to the biocompatible polymer is selected from the group consisting of mucopoloysaccharides, proteins, chondroitin sulfates and cheratan-sulfates.

5. A device according to claim 3, wherein the reactive substance is selected from the group consisting of hyaluronic acid, chondroitin sulfates and cheratan-sulfates.

6. A device according to any one of claim 1 - 5, wherein the biocompatible polymeric body has the structure of a ring having a shape of a the shape of a spherical cap with transverse through orifice

7. A device according to any one of claims 1 - 5, wherein the biocompatible polymeric body has the structure of several concentric spherical rings of different diameters connected to each other.

8. A method of treating deformities of the cornea, comprising the steps of making cavities in the corneal stroma and introducing in said cavity an implant device according to any one of claims 1 - 7.

9. A method according to claim 8, which is intended for the treatment of deformities selected from the group consisting of keratoconus, irregular astigmatisms due to cornea transplants and after Lasik and PRK refractive cornea surgeries.