Medicament coated refractive anterior chamber ocular implant.

IS 2 149 178 T3

DESCRIPTION

Refractive anterior chamber ocular implant, coated with a drug. Background of the invention

The present invention refers to an ocular implant for the divergent anterior chamber covered by a drug to be placed in a phaco eye to correct refractive errors such as myopia, a method for the preparation of said implant and a method for its use. of said implant in a myopic phakic human eye.

It is well known to experts in the field of ophthalmology that the need for ocular implants for the anterior chamber of a phakic eye has existed, and continues to exist, in order to compensate for refractive errors such as high myopia. degree or to create a specific refraction to improve visual function. For example, the US patent No. 4,676,792 (Praeger) discloses the use of a divergent uncoated lens for the anterior chamber having a flat anterior surface and a concave posterior surface in the treatment of myopia. On the other hand, recently in France the use of uncoated implants has been attempted in the surgical treatment of patients with high-grade myopia not satisfactorily corrected with extraocular lenses or contact lenses, as described by Colin et al. In Refractive et al. Corneal Surgery, Vol. 6 (July / August 1990), pages 245-51 and Baikoff et al. In Refractive and Corneal Surgery, Vol. 6 (July / August 1990), pages 252-60.

However, it is recognized by those skilled in the art that there are significant risks to the eye arising from the use of such implants for the anterior chamber. For example, during the insertion process of an implant of this type within the eye, temporary or permanent adhesions of the same can arise in delicate intraocular structures, causing lesions in said structures, which can appear immediately or later. In addition, once the implant is in its final position, it can cause similar adhesions due to mechanical and / or chemical inflammation that gives rise to fibrosis of a progressive nature and to lesions of the intraocular tissue, making subsequent removal of the implant difficult. a complex and dangerous surgical procedure. Other problems associated with these implants are the appearance of cataracts, secondary glaucoma, corneal edema, hyphema and progressive loss of endothelial cellularity in addition to other complications.

As discussed in Ophthalmology Alert, Vol. 1 n^° 11 (November 1990), pages 41-42, various American manufacturers that were in the process of initiating clone trials with ocular implants for the anterior chamber in the United States are likely to abandon them, due to the risks to participants associated with implants and difficulties in obtaining permission from the FDA (Federal Food and Drug Administration) to use such implants. In view of the aforementioned, it would be clearly advantageous to use an ocular implant for the divergent anterior chamber that possessed a compatible pharmacological coating that would improve and / or prevent the appearance of the described problems associated with said implants.

It is also well known to those skilled in the art that an intraocular lens, when surgically placed, is primarily designed to replace a cataract lens removed prior to or during the surgical procedure itself. However, although the implantation of intraocular lenses has represented an important surgical advance, it is known that said implantation causes immediate or delayed lesions of the corneal endothelium, immediate or delayed inflammatory responses in the anterior and / or posterior segments of the eye, immediate or delayed fibrosis. and / or neovascularization and other problems. In general, the phaco eye is more reactive than the aphaic eye, that is, in the phaco eye, inflammatory reactions tend to be more important, leading to a concomitant increase in eye lesions. First, in the aphoakic eye there is no lens that can pull the ciliary body; therefore, the ciliary body is in a "state of rest", tending to suffer a certain degree of atrophy. Therefore, the inflammatory response will be less in the aphoakic eye. Second, the foakic eye has a more flat anterior chamber (that is, the mean anteroposterior depth is less) than the aphakic eye, and the iris has a greater contact surface with the lens. Therefore, if an inflammatory reaction occurs in the phaco eye, there is a greater surface of adherence of the iris to the anterior surface of the lens or anatomical lens.

To overcome the above-described problems associated with the use of intraocular lenses to replace cataract lenses, the use of intraocular lenses with various coatings has been previously disclosed. For example, US patent n^°4,170,043 (Knight et al.) Discloses intraocular lenses coated with an acrylic resin that have a coating that prevents adhesion of the intraocular lens to the corneal endothelium, the coating being polyvinylpyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, hydroxypropyl methylcellulose, dextran, hydroxyethyl starch, methylcellulose, or guar gum. However, some of these coatings have been found to cause inflammatory reactions and have been unsatisfactory in clonal proactivity.

The patent application of the Federal Republic of Germany n^° 2,556,665 discloses coated intraocular lenses in which the coating is a silicone rubber, such as methyl or methylphenyl siloxane. US patent n^°4,240,163 (Galin) discloses coated intraocular lenses in which the coating is a compatible drug such as a sulfated polysaccharide. Also in the product information of Pharmacia AB of Uppsala, Sweden, entitled “Surface Modified IOLs: A New Approach to Cataract Surgery” (“Intraocular lenses (IOLs)

ES 2 149 178 T3 modified surface: a new approach to cataract surgery ”), pages 17-19, intraocular lenses have been disclosed that have a covalent bond of heparin to a polyamine that is ionically adsorbed on the surface of an intraocular lens.

An additional risk to the eye due to the use of such implants for the anterior chamber is the possibility of the implanted lens coming into contact with the cornea and / or coming into contact with the anatomical lens and / or the iris with the resulting complications. . However, the aforementioned possibility of the lens coming into contact with adjacent anatomical structures can be avoided or mitigated by vaulting the lens in such a way as to minimize the chances of this occurring.

In view of all of the above, it will be apparent to those skilled in the art that some of the problems associated with the use of anterior chamber ocular implants used to correct refractive errors in the phakic eye differ from those associated with the use of lenses. intraocular lenses used as substitutes for the lens with surgically removed cataract. For example, the use of implants in the foaquic eye may in fact cause cataract formation in the natural lens that remains in its original location, while the use of intraocular lenses in patients who have a cataract removed cannot induce cataract. effect, since the natural lens is replaced by the intraocular lens.

It is an objective of the present invention to provide an ocular implant for the divergent anterior chamber to be placed in the anterior chamber of an eye having the anatomical lens in its original location. The implant comprises a negative artificial refractive lens having at least one concave surface, a surface coating comprising a compatible sulfated polysaccharide drug, and a means for fixing the artificial lens in the anterior chamber of the eye so as to avoid contact between the implant and the anatomical lens. The implant can be surgically implanted in the phaco eye to compensate for refractive errors, avoiding the concomitant problems previously described. The implant can be subsequently removed from the eye, if necessary.

It is a feature of the present invention that the coating can be attached covalently, by ionic attraction or by hydrogen bonding to the implant surface. It is another feature of the invention that the sulfated polysaccharide coating can be selected from the group consisting of heparin, heparin sulfate, chondroiton sulfate, dermatoan sulfate, chitosan sulfate, xyloan sulfate, dextraon sulfate, and sulfated hyaluroonic acid. It is also another feature of the invention that the coating can further complex with compounds that possess anticoagulant properties, such as antithrombin. It is also another feature of the invention that the coating may additionally comprise one or more compounds capable of absorbing ultraviolet radiation and other short-wavelength radiation.

It is an advantage of the coated implant of the present invention that it prevents attraction and minimizes the adherence of leukocytes, pigmentary granules and intraocular tissue to its surface. It is another advantage of the present invention that said implant prevents the stimulation of leukocyte activity and enzyme secretion that leads to the destruction and dysfunction of the corneal endothelium. It is another characteristic of the present invention that the formation of cataracts secondary to surgical trauma and / or immediate or delayed inflammation can be minimized and / or avoided. It is also another advantage of the present invention that light spots, leukocyte accumulations, vomit reactions, cystoid macular edema, hypopyon, uveotis and secondary glaucoma topically associated by those skilled in the art with the use of implants can be avoided. eyepieces for the anterior chamber.

It is another objective of the present invention to present a method for preparing the ocular implant for the previously described divergent anterior chamber, in which the implant avoids the previously mentioned problems when it is surgically implanted inside the eye, and can be subsequently removed from it. in necessary case.

It is a characteristic of the method of preparation of said implant that the coating can be attached covalently, by ionic attraction or by means of hydrogen bonds to the surface of the implant. It is another feature of this method that the sulfated polysaccharide coating can be selected from the group consisting of heparin, heparin sulfate, chondroiton sulfate, dermatoan sulfate, chitosan sulfate, xylan sulfate, dextroan sulfate, and sulfated hyaluronic acid. It is also another feature of this method that the coating can additionally form complexes with compounds that possess anticoagulant properties, such as antithrombin. It is also another characteristic of this method that the coating may additionally comprise one or more compounds capable of absorbing ultraviolet radiation and other short-wavelength radiation. It is also another feature of this method that a plasma treatment can be used first to treat an uncoated implant, and then the drug can be attached to the plasma-treated surface.

It is an advantage of this method that it avoids attraction and minimizes the adherence of leukocytes, pigmentary granules and intraocular tissue to its surface. Another advantage of this method is that it avoids the stimulation of leukocyte activity and enzyme secretion that leads to the destruction and dysfunction of the corneal endothelium. It is another characteristic of this method that the formation of cataracts secondary to surgical trauma and / or immediate and delayed inflammation can be minimized and / or avoided. It is also another advantage of this method that light spots, leukocyte accumulations, vomit reactions, cystoid macular edema, hypopyon, uveotis and secondary glaucoma topically associated by experts in the field with the use of ocular implants can be avoided.

ES 2 149 178 T3 for the anterior chamber.

It is also another objective of the present invention to disclose a method for the use of the ocular implant for the coated anterior chamber of the present invention in the treatment of myopia, in which the implant is surgically implanted in the phakic eye to compensate refractive errors, thus advantageously avoiding the problems previously described. The implant can be removed later if necessary.

Characteristics of the invention

The present invention is directed to a divergent anterior chamber ocular implant to be placed in the anterior chamber of an eye with the anatomical lens in its original location. The implant comprises an artificial negative refraction lens having at least a concave surface and a surface coating comprising a compatible sulfated polysaccharide-type drug, and a means for fixing the artificial lens in the anterior chamber of the eye to avoid contact between the implant and anatomical lens.

The sulfated polysaccharide is preferably selected from the group consisting of heparin, heparin sulfate, chondroitan sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextraan sulfate, and sulfated hyaluraonic acid, with heparin being particularly preferred. Heparin typically has a molecular weight between about 2,500 and 15,000 daltons, preferably between about 2,500 and 10,000 daltons, and most preferably between about 2,500 and 5,300 daltons. The coating is preferentially attached to the implant surface by ionic attraction, hydrogen bonding, or covalent bonding, with covalent bonding being particularly preferred. The coating typically has a thickness of between approximately 1 / 100,000 mm and 1/100 mm, and constitutes between approximately 1 / 10,000% and approximately 1/10% by weight of the implant. The coating can additionally complex with compounds that possess anticoagulant properties such as antithrombin.

The coated divergent anterior chamber ocular implant of the present invention is advantageous in that it can be implanted in a phakic eye to compensate for refractive errors, furthermore possessing increased biocompatibility in the anterior chamber of the eye, and therefore avoids the problems Typically associated with such implantation, including damage to the corneal endothelium, inflammatory responses in the anterior or posterior segments of the eye, particularly cataract formation in the natural lens that is left in its original location when the anterior chamber refractive implant is placed in the eye.

The present invention is further directed to the method of preparing said divergent coated anterior chamber ocular implant, said method comprising the steps of, first, exposing an uncoated surface of the implant to a plasma to generate a plasma-treated implant that presents a surface containing constituents selected from the group consisting of amines, carboxylic acids, active free radicals and passive free radicals, and, then bond the sulfated polysaccharide drug to the surface of the plasma-treated implant.

The divergent anterior chamber ocular implant of the present invention is useful for the treatment of myopathy by surgical implantation and anchoring of the implant in the anterior chamber of a phakic eye.

Brief description of the drawings

The ocular implant for the divergent anterior chamber of the present invention will be described hereinafter with reference, in part, to the accompanying drawings, in which:

Figure 1 is a top plan view of an embodiment of an ocular implant for the anterior chamber according to the present invention, in which the negative refractive lens is biconcave.

Figure 2 is a lateral cross-sectional view of an eye containing the ocular implant for the implanted bicoancave anterior chamber of Figure 1.

Description of the preferred embodiments

The present invention is directed to a divergent anterior chamber ocular implant to be placed in the anterior chamber of an eye having an anatomical lens in its original location. As used in this description and in the appended claims, the term "divergent anterior chamber ocular implant" specifically refers to a negative refractive lens surgically implanted in a phakic eye to compensate for and / or correct refractive errors, and specifically, it excludes intraocular lenses surgically inserted into the aphakic eye, as disclosed, for example, in US Patent No. 4,240,163 (Galin).

The negative refractive lens used in the present invention has a lens shape with two refractive surfaces, at least one of which is coancave, so that the combined refractive powers of the two surfaces are divergent or negative. Such lenses are typically used in the correction of high-grade myopia.

As previously discussed, uncoated divergent anterior chamber ocular implants are well known to those of skill in the art. The optic part of the implant used in the present invention is preferably manufactured from compounds such as polymethyl methacrylate, poly-2-hydroxyethyl methacrylate, methyl methacrylate copolymers, siloxanylalkyl methacrylate, fluoroalkyl methacrylate and aryl methacrylate, silicone, silicone elastaomers, polysulfones, polyvinyl alcohols, polyethylene oxides, copolymers of fluoroacrylates and methacrylates and polymers and copolymers of hydroxyalkyl methacrylates, such as 2-hydroxyethyl methacrylate, glyceryl methacrylate, 2-hydroxypropyl methacrylate, as well as methacrylic acid, acrylic acid, methacrylamide, acrylamide N-dimethylacrylamide and N-vinylpyrrolidone. Additionally, they can be added to the monomers and / or polymers that constitute the ocular implant to

ES 2 149 178 T3 the anterior chamber, compounds that absorb ultraviolet radiation or other short wavelength radiation (for example less than about 400 nm), such as compounds derived from benzotriazole groups, benzophenone groups or mixtures thereof. Other compounds well known to those skilled in the art can also be used in the manufacture of the anterior chamber ocular implant used in the present invention.

It is well known to those skilled in the art that when placing an implant within the anterior chamber of a phakic eye, it is important to avoid, inter alia, contact between the implant and the anatomical lens located in the posterior chamber. In the present invention, the haptics are integral with the oáptic portion of the implant, and fix or "dominate" the artificial lens in the anterior chamber of the eye to avoid such contact. The haaptics can be of the same material previously described for the oaptic portion of the implant, or they can be made of materials such as polypropylene. Haaptics that can be employed in the implant of the present invention include haaptics such as those described in US Patent No. 4,676,792 (Praeger).

Most divergent anterior chamber implants typically have a total diameter of approximately 12-14 mm, if they are made up of a single piece of silicone or plastic, with an opal diameter of 4-6 mm. The central thickness and the posterior radii of the opal part of the implant vary typically depending on the desired strength and the material used. Such implants can typically weigh up to 25 mg in air, or about 0.5 to 4 mg in aqueous medium. Examples of commercially available uncoated anterior chamber ocular implants include those sold, for example, by Domilens, Inc. of Lyon, France.

The sulfated polysaccharide drug coating used in conjunction with the anterior chamber ocular implant of the present invention is preferably selected from the group consisting of heparin, heparin sulfate, chondroitan sulfate, dermatan sulfate, chitosan sulfate, xylan sulfate, dextraan sulfate, and acid sulfated hyaluronic acid. To be used as a coating, heparin is particularly preferred, having a molecular weight of between approximately 2,500 and 15,000 daltons. Commercially available heparin, which typically has a molecular weight between about 12,000 and 15,000 daltons, can cause platelet agglutination. Consequently, it is more suitable to use a lower molecular weight heparin (a derivative or fraction), with a molecular weight between approximately 2,500 and 10,000 daltons, more preferably between approximately 2,500 and 5,300 daltons and even somewhat higher. These low molecular weight heparins can be prepared by enzymatic hydrolysis or depolymerization of heparin with heparinase as disclosed, for example, in US Pat.^° 3,766,167 (Lasker et al.), Or by depolymerizing residues of commercial bovine or porcine heparin or heparin by reacting heparin with a mixture of ascoarbic acid and hydrogen peroxide, isolating and then fractionating the reaction products by means of They are precipitated using an organic solvent, such as ethanol, methanol, acetone, or methyl ethyl ketone. Commercially available heparin can also be chemically cleaved using nitrous acid to give a lower molecular weight heparin, in the range of about 2,500 to 10,000 daltons, preferably 2,500 to 5,300 daltons.

In a preferred embodiment of the present invention, as shown in Figure 1, the representative ocular implant for the divergent anterior chamber (2) has two haptics (4) and (6) integral with the negative artificial refractive lens (8 ), so that when implanted inside the anterior chamber of the eye, the lens (8) is fixed in such a way as to avoid contact between the implant (2) and the anatomical lens (not shown). In this view, the first surface (10) of the negative refractive lens is visible, with the second surface (12) of the negatively refractory lens located directly below the first surface (10). Both surfaces (10) and (12), as well as haaptics (4) and (6), have a sulfated polysaccharide drug coating (14) (not shown).

As shown in Figure 2, the implant (2) is implanted inside the anterior chamber (16) of the eye (18), with the negative artificial refractory lens (8) held in position or domed by the haptics (4 ) and (6) to avoid contact between the implant (2) and the anatomical lens (20). The implant (2) is also positioned in such a way as to avoid contact with the corneal endothelium (22) of the posterior part of the cornea (24), as well as with the iris (26). In this embodiment, the first surface (10) and the second surface (12) are concave. In other embodiments of the present invention, the first surface (10) and the second surface (12) can be coancave, convex or flat, provided that at least one of the two surfaces (10) or (12) is concave. . The first surface (10) and the second surface (12), as well as the haaptics (4) and (6), are coated with a pharmacological coating (14). Figure 2 does not show the means of anchoring or fixing the haaptics (4) and (6) and the implant (2) in the anterior chamber of the eye. Such means are well known to those skilled in the art; For example, the platforms disclosed in US Patent No.^° 4,676,792 (Praeger).

The coating of the present invention can be attached to the implant surface by any of the unioan methods well known to those skilled in the art, preferably such that the coating is attached to the implant surface by covalent unioan, ionic attraction or unioan. by hydrogen bonding, covalent bonding being particularly preferred. In a particularly preferred embodiment of the present invention, the heparin is covalently attached to the implant surface via an attachment of an end group of the heparin to the implant surface.

In another embodiment I particularly prefer

ES 2 149 178 T3 te, the implant surface is first treated with a plasma to generate a surface containing amine groups, a surface containing carboxylic acids or a surface containing active or passive free radicals, then heparin compounds or compounds are used. derivatives thereof to coat the implant surface. In one embodiment, the plasma treatment is performed by placing the implant in a gaseous atmosphere such as an oxygen-poor atmosphere and subjecting the implant to an electromagnetic field for a given period of time. For example, in one embodiment the implant can be subjected for 1 to 10 minutes, for example 2 minutes, to an electromagnetic field having a frequency between 1 and 50 MHz, for example approximately 10 to 15 MHz, with a corresponding power range from 10 to 500 W / cm², for example about 100 W / cm².

In another embodiment, according to techniques well known to those skilled in the art, the plasma treatment is performed by applying a voltage between electrodes, between which the uncoated implant is placed in the presence of a gas, thus causing a highly ionized gas bombards the implant surface causing the desired constituent (i.e. amine, carboxylic acid, active free radical or passive free radical) remains located on the implant surface. The gas used can comprise a carrier gas, either alone or in combination with other gases. The carrier gas can be any gas, but argan and air are preferred, with argan being used typically. The gas pressure is typically between 1.0 and 3,000 torr. The equipment that can be used to achieve such plasma treatment is well known to those skilled in the art, such as the equipment described in US Pat.^° 4,780,176 (Sudarshan et al.) For washing and plasma etching of a metal substrate. In the present invention, a power input to the electrode between 10 and 500 W can be used to achieve a corresponding potential difference in the space between the electrodes.

To generate an amine-containing surface, a plasma containing ammonia or a material containing primary amines is used. A surface containing carboxylic acids is achieved by an oxidative reaction caused on the surface or by the presence of residual water in the plasma under inert conditions. In this type of embodiment, argan is typically used as carrier gas. Exposure of the surface to a plasma of argan gas at a sufficiently high power causes the physioan of bonds, giving rise to a surface rich in active free radicals, while exposure of the surface to a plasma of oxygen or air under conditions oxidants give rise to a surface rich in passive free radicals.

The method of coating the drug-coated implant of the present invention can be any suitable one well known to those skilled in the coating art, such as dip coating, spray coating and the like, using a suitable solution or dispersion of the drug, dissolved. or dispersed in a suitable solvent or dispersant, such as water, ethanol, and the like, so that the solvent does not affect the optic of the lens. The coating solution or dispersion possesses a conventional drug concentration corresponding to the particular coating technique selected. Typically, after applying the coating to the implant, the implant is dried, for example, by drying at room temperature or higher. If necessary, the coating can be applied repeatedly, to achieve the desired coating weight or thickness. The coating must not affect the transmission of visual light and typically has a thickness between approximately 1 / 100,000 mm and 1/100 mm, and constitutes between 1 / 10,000% and 1/10% by weight approximately of the implant.

Additional drugs and other compounds may also be employed in combination with the compatible sulfated polysaccharide-type drug coating of the present invention. For example, in one embodiment the coating further complexes with antithrombin to result in a coated implant with anticoagulant properties.

Although the inventors do not intend to be bound by a certain theory, it is hypothesized that the coating of the ocular implant for the refractive anterior chamber with the previously specified polysaccharide drug also fills the microscopic fissures present in the uncoated implant, even when these are polished in the highest degree possible. Thus, the implant surface is smoother and less adherent. In addition, the implant surface softens, its surface tension and contact angle are lowered, and it becomes more inert, thereby reducing the potential for progressive endothelial loss. Therefore, it is considered that the coating used according to the present invention creates an increased "inert" state relative to the ocular implant for the divergent anterior chamber, thus making the use of the present invention particularly advantageous in eyes with a history of inflammation.

Furthermore, it is hypothesized that the specified coating alters the abrasive potential of the implant and reduces the trauma associated with insertion and maintenance of the implant. Additionally, the specified coating can reduce the inflammatory potential of the implant and the dangerous sequelae derived from it, including, among other effects, the formation of cataracts. The coated implant can also act as a therapeutic agent to prevent and treat reactions directed against the previously described implant.

The following examples illustrate the preferred embodiments of the implant of the present invention. The following examples will be understood to be illustrative only, not intended to limit the invention in any way.

IS 2 149 178 T3

Example 1

An uncoated divergent anterior chamber ocular implant according to the present invention and possessing surface carboxyl groups is surface coated with low molecular weight heparin (ie, approximately 2,500-5,300 daltons) by the following procedure. The carboxyl group-containing implant surface can preferably be formed by initially incorporating about 5 percent by weight of methacrylic acid in the monomer formulation used to prepare the implant. Alternatively, surface hydraolysis of suspended acrylate or methacrylate groups on the implant surface may be employed, in a manner well known to those skilled in the art. The carboxylic acid groups suspended from the surface of the implant are then reacted with a commercially available diamine, such as hexamethylene diamine or a polymeric diamine such as the series sold under the trade name JEFFAMINE from Texaco Chemical Company, in presence of a water-soluble carbodimide binding agent, to generate an amine grafted surface (through amide bond formation) in which the unbound part of the amine is in the free primary amine form. Low molecular weight heparin containing a terminal aldehyde group is added to the surface grafted with free primary amines, and then the aldehyde group is coupled with the primary amine on the implant surface by means of a water-soluble carbodimide giving rise to a Schiff base. , which is then reduced to form a secondary amine bond or unioan to which the low molecular weight heparin binds.

Example 2

In another preferred embodiment, an uncoated divergent anterior chamber ocular implant is obtained according to Example 1 according to the present invention, which contains surface carboxylic groups. However, instead of reacting the surface carboxylic groups with a diamine, as in Example 1, a terminal aldehyde heparin is first coupled to a diamine. This reaction uses an excess of diamine, such as a water-soluble low molecular weight diamine, which reacts with the terminal aldehyde heparin through one of its amine groups, generating a heparin derivative with an amide bond and with a suspended amino group. free. This water-soluble compound is then purified by dialysis to remove excess unreacted diamine, obtaining the product by lyophilization. The aminated heparin is then reacted with the hydrolyzed surface of the ocular implant for the anterior chamber through its surface carboxylic groups in the presence of a water-soluble carbodiimide coupling agent. Compared to the previously described embodiment in Example 1, this process uses only one coupling reaction on the implant surface instead of two. Example 3

In another preferred embodiment, an uncoated divergent anterior chamber ocular implant according to the present invention is treated with a plasma following the methods previously described to generate a surface containing amine, a surface containing carboxylic acids or a surface containing free radicals. assets or liabilities. If an amine-containing surface is obtained, a terminal aldehyde heparin can be used to coat the implant surface following Example 1. If a surface containing carboxylic acids is obtained, an amino heparin can be used to coat the implant surface according to the Example

two. If a surface containing active or passive free radicals is obtained, compounds containing low or high molecular weight carboxylic amines or carboxylic acids can be reacted with the surface resulting in an implant surface containing, respectively, covalently linked amine or carboxylic acids. , on which the heparin compounds with terminal or amino aldehyde, described respectively in Examples 1 and 2, will be used, to coat the implant surface with heparin. In a particularly preferred embodiment, the plasma treatment employed will act to allow traces of surface moisture on the uncoated implant to become a passive free radical coupling agent through the formation of peroxide groups.

With respect to the above examples, if it is desired or desired to increase the anticoagulant properties, antithrombin can be added to form complexes with the binding sites of the heparinized surface. Similarly, if additional ultraviolet radiation absorption capacity is desired, compounds with the ability to coat the ocular implant for the divergent anterior chamber can be added to the monomer mixture used to coat the divergent anterior chamber with a compatible sulfated polysaccharide type drug according to the present invention. absorption of ultraviolet radiation, such as compounds containing benzotriazole groups, benzophenone and mixtures thereof.

The present invention is also directed to a myopathic treatment method that comprises surgical implantation and anchoring in the anterior chamber of a phakic eye of a divergent lens that comprises at least one concave surface and a surface coating that comprises a drug of the type compatible sulfated polysaccharide.

Again, although it is not intended to be bound by a particular theory, it is hypothesized that the present invention, in which the coating is bonded to the implant surface as described, has advantages over intraocular lenses that employ the joint. heparin covalent to a polyamine that is ioanically adsorbed on the lens surface, by the fact that the coating of the present invention is less likely to be released and dissipated in the aqueous humor of the anterior and posterior chambers of the eye.

Although the present invention has been illustrated with reference to specific embodiments,

It will be apparent to those skilled in the art that various changes and modifications can be made which are clearly within the scope of the invention.