JPH01249048A - Corneal lens device - Google Patents

Abstract

PURPOSE: To provide an artificial lens for cornea, making possible to effectively accelerate the curing of an injured cornea in vivo by composing so that the effective amount of an additive component in the structural body of artificial lens accelerates at least either the growth of the epithelial cell of a cornea upon the artificial lens or adhesion of the cornea in vivo. CONSTITUTION: When a surgery is completed, the layer of an epithelial cell 112 is grown upon the implant segment 110 of a cornea, and fixed to the implant segment 110 of the cornea, (i.e., adhered). The implant segment 110 of the cornea is made of a water permeable and optically transparent polymeric material such as a poly(hydroxyethyl) methacrylate having a biocompatibility to be adequate to use as a implant for the cornea. A fibronectin or a fibronectin derivative is covalently bonded to the polymeric material for forming the implant segment 110 of the cornea. This fibronectin or fibronectin derivative is equally dispersed into the polymeric material, and compounded in the ratio of approximately 1wt.% of the implant segment 110 of the cornea.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a corneal lens device that can be surgically implanted into a living cornea.
or, in another embodiment, relates to a corneal lens device suitable for placement in close proximity to a damaged living cornea. More specifically, the present invention provides a corneal lens device capable of promoting at least one of the growth or adhesion of a living cornea (e.g., corneal epithelium) to a post-operative corneal graft, or a corneal lens device capable of promoting healing of a damaged cornea. The present invention relates to a corneal lens device capable of correcting visual impairments such as refractive errors.

The cornea has five layers: an outer layer made of epithelial cells,
It is composed of Bowman's membrane immediately behind this epithelial cell layer, stroma immediately behind Bowman's membrane, Descemet's membrane immediately behind the stroma, and endothelium immediately behind Descemet's membrane. There is. Many surgical procedures have been performed to implant corrective lens structures into one or more of these corneal constructs. For example, one form of ophthalmic surgery involves removing an epithelial cell layer and placing and fixing a corrective lens structure at the location where the epithelial cell layer has been removed.

Another form of ophthalmic surgery involves removing a portion of the epithelial cell layer and then removing a wedge-shaped annular region from Bowman's membrane and the underlying stroma. Next, from the rear end of the annular groove thus formed, an incision is made radially outward within the annular region to form a flap. The corrective lens structure is then attached by inserting the wings of the corrective lens structure under the corneal flap and secured in place, such as by suturing. It is also possible to place the entire corrective lens structure within the stroma. This surgery involves incision of the cornea to gain access to the stroma and damage to the stroma by placing a corrective lens structure within the stroma.

In each of these surgical procedures, the long-term growth potential of the lens implant, i.e., the ability of the cornea (e.g., epithelial cells) to grow onto and/or adhere to the lens implant (corrective lens structure), is important. is strongly desired (even necessary). Until now, corneal transplant surgery as described above could not be performed because such growth and adhesion could not be achieved, which has been a major problem.

One proposal to solve this problem is to instill an aqueous fibronectin solution into the cornea after surgery to increase epithelial cell growth. However, the overall success of this attempt has not yet been demonstrated. For example, dropping an aqueous fibronectin solution is troublesome and causes discomfort because it must be done very tightly. Further, even if an aqueous fibronectin solution is frequently injected, it is very difficult to retain an effective amount of fibronectin in the eye. This is because fibronectin is washed away from the eye by natural cleaning actions (eg, the action of tears).

For example, sports-related accidents and other accidents often also damage the cornea. Since such corneal damage can be relatively uncomfortable and/or have a detrimental effect on the injured person's vision, it is highly desirable to heal the damage as soon as possible.

Therefore, an object of the present invention is to provide a corneal lens device that can effectively promote the growth and/or adhesion of a living cornea to a lens structure and/or the healing of a damaged living cornea. Thus, with the use of the corneal lens device of the present invention, rapid and successful recovery from eye surgery or corneal injury can be achieved. Additionally, these beneficial results can be achieved with little or no additional effort, care, or treatment, eg, on a portion of the patient's body. For example, there is no need to repeatedly administer the drug or its drops to the eye.

In one embodiment, the corneal lens device of the invention is associated with a lens means or lens structure that can be surgically associated with, preferably attached to, the natural cornea of the eye; promoting at least one of growth of the corneal epithelial cells onto the lens structure and adhesion of the living cornea to the lens structure;
and an effective amount of at least one additional ingredient. Said lens means, for example when surgically implanted on or into a living cornea, is intended to alter the optical properties of the eye to which this living cornea is associated (e.g. to correct impaired visual acuity). act.

The above-mentioned "promoting at least one of the growth of corneal epithelial cells onto the lens structure and the adhesion of the living cornea to the lens structure" means that the additive component of the present invention promotes the growth of corneal epithelial cells onto the lens structure and the adhesion of the living cornea to the lens structure. Encouraging and/or facilitating cell growth (which is often naturally synthesized) and/or adhesion of corneal cells (e.g., newly formed epithelial cells) to the lens structure It means to do something. Successful completion of corneal lens device surgery requires both epithelial cell growth and adhesion to occur.

Preferably, the lens structure is attached to the living cornea by a surgical technique such as suturing. Further, the additive component is effective in promoting adhesion of the living cornea to the lens structure. Once such adhesions have taken place, the corneal cells themselves act to hold the lens structure in place, eg, after the suture is removed or dissolved.

The additive component can be associated with the lens structure, such as by being attached, fixed or deposited, at or near the outer surface of the lens structure. However, the additive components are preferably disposed (ie, incorporated) within the lens structure, and more preferably substantially uniformly incorporated within the lens structure. In embodiments in which the corneal lens device is surgically associated with the cornea, such as embodiments in which the corneal lens device is surgically implanted into the cornea, the additive components should not be substantially degraded in use, i.e., in the patient's eye. , and preferably not leached or extracted from the lens structure. In one particularly advantageous embodiment, the additive component is chemically bonded to the lens structure;
Especially covalently bonded. Such covalent bonding allows the additive components to be retained within the lens structure, minimizing the amount of additive components lost during use.

A corneal lens device in another embodiment of the invention includes a lens means or lens structure that can be placed in close proximity to (e.g., directly over) a damaged living cornea; For structures, e.g. fixed,
and at least one additional component associated therewith by way of attachment, deposition, bonding, etc. The additive components are released or dissociated from the associated lens structure over an extended period of time, preferably at least about 12 hours, and more preferably from about 2 days to about 20 days or more. The corneal lens device in this embodiment of the invention can be configured as a contact lens that is placed substantially directly on the cornea. This approach of the present invention to deliver additive components to an injured living cornea is superior to the conventional method of repeatedly instilling small drops of drug into the eye. For example, dissociation of the additive component from the lens structure can be more effectively controlled such that an effective amount of the additive component to promote corneal healing is substantially continuously provided. It also eliminates the need to repeatedly and continuously apply drops of medication to an injured eye, which can be cumbersome and uncomfortable.

In this embodiment, the additive component is placed (compounded) on or near the outer surface of the lens structure. In order to dissociate the additive component at a more uniform timing, it is necessary to In the case of the "contact lens" embodiment of the present invention, it is preferable to physically associate the additive components with the lens structure rather than chemically bonding them. preferred.The important thing is that
The objective is to enable the additive components to be dissociated from the lens structure over a long period of time. As mentioned above, when the additive component is bonded to the lens structure by a chemical bond such as a covalent bond, substantially no dissociation of the additive component may occur. It has been found that the dissociation of the additive components is very important in the case of the "contact lens" embodiment of the invention.

The lens structure in the "contact lens" embodiment may or may not be configured to alter optical properties (eg, to correct vision in an injured eye). The primary function of the lens structure in this "contact lens" embodiment is to form a substrate for effective and timely dissociation of additive components. Also, another useful feature of this lens structure is
The purpose is to protect the injured living cornea.

Any suitable additive ingredient may be used in the present invention as long as it functions as described above and does not have a substantial or unacceptable adverse effect on the eye or the patient being treated. can do. In this application, “
"Additional components" refers to components that have the above-mentioned functions and are not conventionally included in the above-mentioned lens structures.
(singular or plural). Effective additive components in the present invention include various growth promoters and adhesion promoters that promote the growth and adhesion of corneal cells as described above. In one embodiment, the additional component is a protein. Effective additive ingredients include the group consisting of fibronectin, collagen cell-binding protein, anti-gelatin agent, cold-insoluble globulin, chondronectin, laminin, epithelial growth promoter (EGF), macer adhesion protein, derivatives thereof, and mixtures thereof. There are some selected from.

The lens means or lens structure may be any suitable material that does not have a substantial adverse or deleterious effect on the eye or the patient being treated and that can be constructed to function as described above. Can be made of structural material(s).

The lens structure must also have water permeability and nutrient permeability, so that the lens structure does not unduly impede the flow of nutrients to the corneal epithelium. Although the lens structure can be made from natural materials, it is preferably made from synthetic materials, and more preferably from synthetic polymeric materials. Materials that are physically and chemically blended or combined natural and synthetic materials may also be used. A large number of polymeric materials have been proposed for use in lens structures.

Synthetic polymeric materials useful in the lens structures of the present invention include homopolymers and copolymers derived from monoolefins and diolefins, mixtures of these polymers, polystyrene, copolymers of styrene and alpha-methylstyrene, Graft copolymers of styrene, halogen-containing vinyl polymers, polymers derived from α- and β-unsaturated fatty acids and their derivatives, polymers derived from unsaturated alcohols and amines, homopolymers derived from epoxy compounds Polymers and copolymers 1, crosslinked polymers derived from polyacetals, polyalkylene oxides, polyphenylene oxides, polyurethanes and polyureas, polycarbonates, polysulfones, polyamides and copolyamides, polyesters, aldehydes with phenols added , urea resins or melamine resins, alkyd resins, unsaturated polyester resins, silicone resins, hydrogel-forming polymers, and the like.

The lens structure of the corneal lens device of the present invention comprises polymers derived from α- and β-unsaturated fatty acids and derivatives thereof,
It is preferably made of polyurethane, silicone resin, and hydrogel-forming polymers, and hydrogel-forming polymers are particularly useful because they have significant water permeability.

Covalently bonding the additive component to the lens structure requires derivatization of either or both of the additive component and the lens structure. The derivative(s) to be employed will be determined based on, for example, the particular lens structure material used and the particular additive components used. In one particularly useful embodiment, one of the lens structure materials or additive components reacts with the difunctional formulation. That is, one functional group of the bifunctional formulation reacts and covalently bonds with one of the lens structure materials or additive components, and the other functional group covalently bonds with the other lens structure material or additive component. be used as much as possible.

Any bifunctional formulation that can be covalently bonded to both the material of the particular lens structure used and the additive components can be used. Of course, the difunctional formulation to be used must not have any significant adverse effects during use of the corneal lens device.

Examples of difunctional additives that can be used in the lens structure materials and additives include aldehydes, such as glutaraldehyde, and imides, such as carbodiimides.

The difunctional formulation may react with the lens structure materials and additive components in a separate reaction step, or it may react with any reactants present in a single reaction step.

In another example, covalent bonding between the lens structure and the additive components can be facilitated or induced by, for example, exposing the materials and formulations to gamma radiation or plasma treatment.

These and other features and advantages of the invention will become apparent from the following detailed description of embodiments of the invention, taken in conjunction with the accompanying drawings.

FIG. 1 shows a corneal graft.
) The entire corneal lens device of the present invention in the form of
10, the corneal graft 110 is placed on the Bowman's membrane 111 of the living cornea 114 and attached (sutured) to the Bowman's membrane. In addition, the cornea 114
includes an epithelial cell layer 112, stroma 113, and Descemet's membrane 115.
and endothelium 117. A corneal lens device or corneal graft 110 (the corneal graft is configured to correct one or more visual defects caused by a defect in the cornea 114 or one or more other structures making up the eye) ) is placed at a location created by surgically stripping or scraping a desired area of epithelial cell layer 112 and secured there by suturing to Bowman's membrane 111.

The corneal graft 110 is positioned relative to the cornea 114 so as to be coaxial with the optical axis of the eye, as shown in FIG.

Upon completion of the surgical procedure, an epithelial cell layer 112 grows over and attaches to (ie, is fused to) the corneal graft 110.

Corneal graft 110 is made of a water-permeable, optically transparent polymeric material, such as poly(hydroxyethyl) methacrylate, which is biocompatible and suitable for use as a corneal graft. Fibronectin or fibronectin derivatives are covalently bonded to the polymeric material forming corneal graft 110. The fibronectin or fibronectin derivative is substantially uniformly dispersed in the polymeric material and is incorporated at approximately 1% by weight of the corneal graft 110.

After the corneal graft 110 is attached to the Bowman's membrane 111, the fibronectin or fibronectin derivative of the corneal graft 110 causes the epithelial cell layer 112 to grow onto the corneal graft 110 and to the epithelial cell layer 112 to the corneal graft 110. adhesion is promoted. Eventually, the epithelial cell layer 112 will grow to completely cover the corneal graft 110 and become securely attached to the corneal graft 110. The rate at which this growth and fixation occurs is significantly faster in the corneal graft 110 of the present invention than in corneal grafts that do not contain fibronectin or equivalent substances.

Of course, all or a portion of the fibronectin or its derivatives covalently bound to the corneal graft 110 may be added to the growth of the epithelial cell layer 112 onto the corneal graft 110 and the corneal graft 1.
It will be appreciated that one or more other additive components can be substituted that can effectively promote the fixation or adhesion of the epithelial cell layer 112 to the epithelial cell layer 10.

In FIG. 2, another corneal implant, a corneal lens device in the form of a superior corneal fixation lens (indicated in its entirety by the numeral 210), has been placed and attached onto Porman's membrane 211 of a native cornea 214 ( (sutured) state is shown. Each element (component) of the living cornea 214 in FIG.
The reference numbers are 100 larger than the reference numbers assigned to each component of the living cornea 114 shown in FIG. The corneal graft 210 has a circular lens portion 216
and an annular wing portion 218 surrounding the lens portion 216. The corneal graft 210 is received in a region 220 where the annular wing 218 is annularly scraped and with its lens portion 216 coaxial with the optical axis of the eye, as shown in FIG. In this way,
It is placed relative to the living cornea 214. The area 220 is
It can be formed by peeling off and/or scraping a portion of the epithelial cell layer 212 and Bowman's membrane 211. Apparatus and techniques useful for performing this stripping and scraping are disclosed in U.S. Patent Application No. 10, filed September 29, 1987.
No. 2,344.

The corneal graft 210 (particularly its lens portion 216) is
It is configured to correct one or more problems caused by defects in the native cornea 214 or one or more other components of the eye.

As shown in FIG. 2, once the surgical procedure to place the corneal graft 210 in place has been performed, an epithelial cell layer 212 grows over the corneal graft 210 and
10 (i.e., fused).

Corneal graft 210 is made of substantially the same material as corneal graft 110.

The corneal graft 210 is attached to the living cornea 2 as shown in FIG.
After being attached to the corneal graft 14, fibronectin or its derivative contained in the corneal graft 210 promotes the growth of the epithelial cell layer 212 onto the corneal graft 210 and the adhesion of the epithelial cell layer 212 to the corneal graft 210. be done. Eventually, the epithelial cells N212 grow to completely cover the corneal graft 210 and are securely fixed to the corneal graft 210. The rate at which this growth and fixation occurs is significantly faster in the corneal graft 210 of the present invention than in corneal grafts that do not contain fibronectin or equivalent substances.

As in the case of the corneal graft 110, instead of all or part of fibronectin or its derivative, the corneal graft 21
Other additive components can be used that can effectively promote the growth of the epithelial cell layer 212 onto the corneal graft 210 and/or the adhesion or attachment of the epithelial cell layer 212 to the corneal graft 210.

FIG. 3 shows a corneal lens device in the form of an intrastromal lens (indicated in its entirety by the numeral 310) positioned within the stroma 313 of a living cornea 314. Third
The reference number of each element (component) of the living cornea 314 shown in the figure is indicated by a number 200 larger than the reference number given to each constituent of the living cornea 114 shown in FIG.

Intrastromal lens 310 is positioned and secured within stroma 313 using conventional surgical techniques such that lens 310 is coaxial with the optical axis of the eye. lens 3
10 is configured to correct one or more visual problems caused by defects in the native cornea 314 or one or more other components of the eye.

Intracortical lens 310 is made of substantially the same material as corneal implant 110.

The intrastromal lens 310 is inserted into the stroma 3 as shown in FIG.
After the lens 310 is surgically implanted into the lens 310, the fibronectin or its derivative contained in the lens 310 promotes adhesion of the tissue of the stroma 313 to the lens 310. Eventually, the stroma 313 is securely fixed to the lens 310. The rate at which this fixation occurs is significantly faster in the intrastromal lens 310 of the present invention than in intrastromal lenses that do not contain fibronectin or equivalent substances.

In place of all or part of fibronectin or its derivatives, other additive components can be used in the lens 310 that can effectively promote stromal adhesion or attachment to the intrastromal lens 310.

In FIG. 4, a corneal lens device in the form of a contact lens (indicated in its entirety by the number 410) is shown on a living cornea 410.
4 is shown arranged on the epithelial cell layer 412. Although there is natural lubrication or moisture between the contact lens 410 and the epithelial cell layer 412,
Not shown.

In addition to the epithelial cell layer 412, the living cornea 414 further includes Bowman's membrane 411, stroma 413, Descemet's membrane 415, and endothelium 4.
It has 17.

Contact lens 410 is made of a material such as poly(hydroxyethyl) methacrylate that is biocompatible and suitable for use as a contact lens structure.
Made of optically transparent material that is water permeable. This polymeric material contains approximately 1% by weight of the contact lens 410.
, the fibronectin is physically mixed and substantially uniformly dispersed. The contact lens 410 may be configured to correct one or more vision defects caused by a defect in the native cornea 414 or one or more other components of the eye, or It can also be configured as a non-corrective contact lens. What is important is that the fibronectin in the contact lens 410 is dissociated from the contact lens 410 over a long period of time, so that healing of the living cornea 414 can be promoted.

When the epithelial cell layer 412 of the living cornea 414 is damaged due to an accident, healing is required. In such a case,
A contact lens 410 is placed near the damaged area of the epithelial cell layer 412. This dissociates fibronectin from the contact lens 410 over a period of time and promotes the necessary healing of the epithelial cell layer 412.

This method of applying fibronectin to the damaged epithelial cell layer 412 has a significant advantage over the method of dropping an aqueous solution containing fibronectin. That is, according to the former method, fibronectin can be continuously supplied to the epithelial cell layer 412 instead of being intermittently supplied to the epithelial cell layer 412 in the form of droplets as in the latter method. Furthermore, by configuring the present invention so that fibronectin can be gradually dissociated from the contact lens 410, the amount of fibronectin applied can be adjusted more effectively, and this growth promoter can therefore be used more effectively. . If desired, fibronectin can be microencapsulated within contact lens 410, allowing for finer control over the timely dissociation of fibronectin.

Of course, all or a portion of the fibronectin in contact lens 410 can be replaced with one or more other additive components effective in promoting healing of epithelial cell layer 412.

Although various specific examples and examples of the present invention have been described above, the present invention is not limited to these examples and examples, and can be implemented in various ways within the scope of the claims.

[Brief explanation of the drawing]

FIG. 1 is an enlarged axial cross-sectional view showing the corneal lens device of the present invention attached to the cornea. FIG. 2 is an enlarged axial cross-sectional view showing another corneal lens device of the present invention attached to the cornea. FIG. 3 is an enlarged axial cross-sectional view showing the corneal lens device of the present invention inserted into the stroma of the cornea. FIG. 4 is an enlarged axial cross-sectional view showing the corneal lens device of the present invention in contact with the cornea. 110... Corneal lens device (corneal graft), 210...
・・Corneal lens device (corneal graft, superior corneal fixation lens)
, 310... corneal lens device (intrastromal lens), 410
...Cornea lens device (contact lens), 111.
211.311.411...Bowman membrane, 112.2
12.312.412...Epithelial cell layer, 113.21
3.313.413... stroma, 114.214.31
4.414... Living cornea, 115.215.315.
415...Descemet's membrane, 117.217.317.41
7... Endothelium, 216... Lens portion, 218... Wing portion, 220... Annular scraping area.

Claims (8)

[Claims] (1) having a lens means surgically attachable to the natural cornea of an eye to alter the optical properties of the eye, and an effective amount of at least one additive component covalently bonded to the lens means; a corneal lens, wherein the additional component is configured to promote at least one of the growth of epithelial cells of the cornea onto the lens means and the adhesion of the living cornea to the lens means. Device. (2) The lens means is attached to the living cornea, and the additive component is configured to promote adhesion of the living cornea to the lens means. lens device. 3. A corneal lens device according to claims 1 and 2, wherein the additive component is covalently bonded to the lens means at or near the outer surface of the lens means. (4) The corneal lens device according to claim 1 or 2, wherein the additive component is substantially uniformly blended within the lens means. (5) A corneal lens device according to any one of claims 1 to 4, characterized in that the lens means is made of a water-permeable synthetic polymer material. 6. The corneal lens device of claim 5, wherein the synthetic polymeric material is a hydrogel-forming polymer. (7) The additional components include fibronectin, collagen cell-binding protein, anti-gelatin agent, biologically active polypeptide, cold-insoluble globulin, chondronectin, laminin, epithelial growth promoter, maser adhesion protein, derivatives thereof, The corneal lens device according to any one of claims 1 to 6, wherein the corneal lens device is selected from the group consisting of: and a mixture thereof. (8) Claims 1 to 6, wherein the additional component is selected from the group consisting of fibronectin, a fibronectin derivative, an epithelial growth promoter, a derivative of an epithelial growth promoter, and a mixture thereof. The corneal lens device according to any one of the above.