Corneal reinforcement with injectable hardenable biomaterial application

Abstract

The invention relates to biocompatible compositions that can be injected into the cornea and hardened by UV or visible light.

Description

[0001] DESCRIPTION

[0002] CORNEAL REINFORCEMENT WITH INJECTABLE HARDENABLE BIOMATERIAL APPLICATION

[0003] Technical Field of the Invention

[0004] The present invention relates to biocompatible compositions that can be injected into the cornea and hardened by UV or visible light for use in the treatment of keratoconus.

[0005] State of the Art (Prior Art)

[0006] Keratoconus is an uncommon corneal disorder where the central or paracentral cornea undergoes progressive thinning and steepening, causing irregular astigmatism.

[0007] Treatment for keratoconus varies depending on the symptoms. When the symptoms are mild, vision can be improved with glasses, however, then it may be necessary to wear special hard contact lenses to help keep vision in the correct focus.

[0008] Other ways that keratoconus can be treated are as follows:

[0009] Intacs: These are small curved devices that are surgically inserted into the cornea. Intacs help flatten the curvature of the cornea to improve vision. Channel creation in these rings is performed by femtosecond laser, but this material is hard and thick. The goal is to make the corneal shape upright.

[0010] Collagen cross -linking: A special UV light and eye drops are used to reinforce the cornea. Doing this helps flatten or harden the cornea, preventing it from swelling further.

[0011] Corneal transplantation: When symptoms are severe, a corneal transplant is recommended. All or part of the diseased cornea is replaced with corneal tissue from a healthy donor.

[0012] There are some disadvantages of the keratoconus treatments outlined above. First, complications such as corneal rupture can be observed because a hard material is used in applications called corneal rings or intacs among the methods. The second problem is that the part that is reinforced by cross-linking is only the corneal tissue itself, and sometimes the thinning of the corneal tissue cannot be stopped with this application.

[0013] Brief Description and Objects of the Invention

[0014] The advantages provided by the present invention are as follows:

[0015] - Injection of a soft material into the channels created in the cornea eliminates the complications that may occur with a hard ring.

[0016] -With this method, cross-linking is performed under light (UV or visible light) in the presence of a photoinitiator to both the corneal tissue and the material injected into the cornea, thus hardening and reinforcing the cornea, and a decrease in steepening is observed by crosslinking both the tissue and the material.

[0017] Detailed Description of the Invention

[0018] The proposed invention comprises biocompatible material compositions that can be injected into the cornea through channels created by a femtosecond laser and can be hardened by UV or visible light.

[0019] It is important that the materials to be injected into the cornea are biocompatible, transparent and have mechanical properties similar to the corneal tissue in order to fully integrate with the cornea. In addition, after the biocompatible material is injected into the cornea, it must harden in a short time under UV or violet light or femtosecond laser light. The materials mentioned within the scope of the invention provide these properties.

[0020] The material compositions that can be injected into the cornea and the photoinitiator combinations to be used therewith that can be used in alternative applications of the invention are listed below:

[0021] - Composition comprising a solution of silk fibroin and a mixture of riboflavin and sodium persulfate as photoinitiator - Composition comprising a mixture of silk fibroin, collagen type I, collagen type IV and collagen type V and a mixture of riboflavin and sodium persulfate as photoinitiator

[0022] - Composition comprising gelatin methacryloyl (GelMA) and 2-Hydroxy-4'-(2- hydroxyethoxy)-2-methylpropiophenone (Irgacure2959®) as photoinitiator

[0023] - Composition comprising gelatin methacryloyl (GelMA) and lithium phenyl-2,4,6- trimethylbenzoylphosphinate (LAP) as photoinitiator

[0024] - Composition comprising a mixture of gelatin methacryloyl (GelMA), collagen type I, collagen type IV and collagen type V, and 2-Hydroxy-4'-(2-hydroxyethoxy)-2- methylpropiophenone (Irgacure2959®) as photoinitiator

[0025] - Composition comprising a mixture of gelatin methacryloyl (GelMA), collagen type I, collagen type IV and collagen type V, and lithium phenyl-2,4,6- trimethylbenzoylphosphinate (LAP) as photoinitiator

[0026] - Composition comprising a mixture of silk fibroin and gelatin methacryloyl (GelMA), and 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure2959®) as photoinitiator

[0027] - Composition comprising a mixture of silk fibroin and gelatin methacryloyl (GelMA), and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as photoinitiator.

[0028] The reason for using collagen type I, collagen type IV and collagen type V among collagen types within the scope of the invention is that these types are collagen types found in the corneal tissue. Although these collagen types can be included alone in the content of the composition, they can also be included in a mixture of at least two. If they are included in the content of the composition as a mixture, they provide the composition with the ability to better imitate / mimic the cornea.

[0029] In the invention, a low concentration of sodium persulfate is used in addition to riboflavin to reinforce the binding in case a sufficient amount of cross-linking cannot be achieved under light during application. Riboflavin must necessarily be used in combination with sodium persulfate. Otherwise, curing does not occur.

[0030] The silk fibroin material in the alternative composition embodiment of the invention exhibits a very good adhesion behavior to the cornea under light, so the composition containing silk fibroin has the potential to provide high performance in the field of application. The reason for using gelatin methacryloyl (GelMA) in the alternative composition embodiment of the invention is that it is a material that has been studied extensively in tissue engineering applications and has the ability to imitate real tissue very well due to its chemical structure.

Claims

CLAIMS1. An injectable composition for use in the treatment of keratoconus, characterized in that it comprises: a) a component comprising at least one selected from, or a mixture of at least two of, silk fibroin, gelatin methacryloyl, collagen type I, collagen type IV or collagen type V, and b) at least one photoinitiator selected from the mixture of riboflavin and sodium persulfate, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, or lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP).

2. A composition according to Claim 1, characterized in that it comprises at least a mixture of collagen type I, collagen type IV, collagen type V.