NO20023343L - Coating of implantable ophthalmic lenses to reduce edge glare - Google Patents

Description

The field of invention

The present invention relates to coatings for implantable ophthalmic lenses. In particular, the present invention relates to hydrophilic coatings which are applied to the edge of implantable ophthalmic lenses.

The background of the invention

Both hard and soft implantable ophthalmic lens materials are known. The most common hard material used in ophthalmic implants is polymethyl methacrylate ("PMMA"). Soft intraocular lens ("IOL") materials can generally be divided into three categories: silicon materials, hydrogel materials, and non-hydrogel ("hydrophobic") (meth)acrylic materials. See, for example, Foldable Intraocular Lenses, Ed. Martin et al., Slack Incorporated, Thorofare, New Jersey (1993). For purposes within the present application are hydrophobic

(meth)acrylic materials (meth)acrylic materials that absorb less than about 5% water at room temperature.

As described in U.S. Patent No. 5,755,786, IOLs, particularly IOLs made for implantation through a small incision, can suffer from an edge glare problem. The invention described in the '786 patent reduces edge glare by including means, such as a plurality of v-shaped depressions, on the optical edge surface to reflect visible light contacting the edge surface away from the patient's retina.

Other methods of reducing edge glare include those described in U.S. Pat. Patent No. 5,693,093; 5,769,889; 4,808,181; and 4,605,409.

Summary of the invention

The present invention relates to hydrophilic coating compositions for surgical implants, especially ophthalmic implants comprising silicon or hydrophobic (meth)acrylic materials. More particularly, the present invention relates to a coating material comprising an ophthalmically acceptable hydrophobic (meth)acrylic polymer and an ophthalmically acceptable hydrophilic polymer.

The present invention also relates to a method for reducing edge glare in implantable ophthalmic lenses. The method comprises applying a coating comprising an ophthalmically acceptable hydrophobic (meth)acrylic polymer and an ophthalmically acceptable hydrophilic polymer to an implant's optical edge surface. When the coating is hydrated, it is cloudy or opaque and reduces or eliminates edge glare.

Detailed description of the invention

Unless otherwise indicated, all amounts are expressed as % (w/w).

As used herein, hydrophobic "(meth)acrylic polymer" means a hydrophobic methacrylic polymer, a hydrophobic acrylic polymer, or a hydrophobic polymer containing both methacrylic and acrylic functional groups. As used herein, "hydrophobic" means that the materials absorb less than about 5% water at room temperature.

The coating material of the present invention comprises an ophthalmically acceptable hydrophobic (meth)acrylic polymer and a hydrophilic polymer. When the coating material is hydrated, it has a Tg of less than 37°C, and preferably less than 15°C. The hydrophobic (meth)acrylic polymer ingredient in the coating material is preferably sticky to assist in the application of the coating material to the substrate. Many ophthalmically acceptable hydrophobic (meth)acrylic polymers are known, including those described in U.S. Pat. Patent No. 5,290,892; 5,693,095; and 5,331,073, the entire contents of which are hereby incorporated by reference. Although aliphatic (meth)acrylate monomers may be used to form the hydrophobic (meth)acrylic polymer, the hydrophobic (meth)acrylate polymer preferably comprises at least one (meth)acrylic monomer containing an aromatic group, such as the materials defined in US 5,693,095:

wherein: X is H or CH3;

m is 0-6;

Y is nothing, O, S or NR, wherein R is H, CH3, CnH2n+1(n=1-10), iso-OC3H7, C6H5 or CH2C6HS; and Ar is any aromatic ring which may be unsubstituted or substituted with CH3, C2H5, n-C3H7, iso-C3H7, OCH3, C6Hn, Cl, Br, C6HS or CH2C6H5.

Suitable hydrophobic (meth)acrylic polymers include copolymers of 2-phenylethyl methacrylate (2-PEMA) and 2-phenylethyl acrylate (2-PEA).

After selecting the (meth)acrylic monomer(s), the hydrophobic (meth)acrylic polymer is formed by using an initiator (generally about 2% or less). Any type of polymerization initiator can be used, including thermal initiators and photoinitiators. A preferred initiator is the benzoyl phosphine oxide initiator, 2,4,6-trimethyl-benzoyldiphenyl phosphine oxide ("TPO"), which can be activated by blue light or UV irradiation. Suitable thermal initiators include the conventional peroxides t-butyl-peroctoate and bis-azoiso-butronitrile. Suitable UV initiators include benzoin methyl ether, Darocur 1173 and Darocur 4265 UV initiators.

The hydrophobic (meth)acrylic polymer optionally contains one or more ingredients selected from the group consisting of UV absorbers which are copolymerizable with the other (meth)acrylic ingredients; blue light-blocking dyes that are copolymerizable with the others

(meth)acrylic ingredients; and chain transfer agents to minimize cross-linking.

Ultraviolet absorbing chromophores can be any compound that absorbs light having a wavelength shorter than about 400 nm, but which does not absorb any significant amounts of visible light. Suitable copolymerizable ultraviolet absorbing compounds are the substituted 2-hydroxybenzophenones disclosed in U.S. Patent No. 4,304,895 and the 2-hydroxy-5-acryloxyphenyl-2H-benzotriazoles disclosed in U.S. Patent No. 4,528,311. The most preferred ultraviolet absorbing compound is 2-(3'-methallyl-2'-hydroxy-5'-methylphenyl)benzotriazole. Suitable polymerizable blue light blocking chromophores include those disclosed in U.S. Patent No. 5,470,932. If a blue light activated polymerization initiator is selected and a blue light blocking dye is added, the polymerization initiator identity or concentration may need to be adjusted to minimize any interference.

Chain transfer agents, if present, are typically added in an amount ranging from 0.01 to 0.4%. Many chain transfer agents are known in the art. Examples of suitable chain transfer agents include 1-dodecanethiol and 2-mer-captoethanol.

The hydrophilic polymer contained in the coating materials of the present invention may be any ophthalmically acceptable hydrophilic polymer. Suitable hydrophilic polymers include, but are not limited to, polyhydroxyethyl methacrylate (polyHEMA); polyacrylamide; polyglyceryl methacrylate and polyvinyl pyrrolidone (PVP). The most preferred hydrophilic polymer is PVP. These hydrophilic polymers are commercially available or can be made using known methods and are preferably obtained in a purified form to minimize extractable materials upon implantation of the coated IOL.

The hydrophilic polymer preferably has a molecular weight (weight average) in the range 2,500-100,000. It is important that the molecular weight of the hydrophilic polymer is large enough and is present in the hydrogel coating material in a sufficient amount to form hydrophilic domains capable of scattering light. The hydrophilic polymer should not be too small, otherwise a significant amount of it may leak out of the coating after the coating is applied to the IOL. The hydrophilic polymer should not be too large, otherwise it may affect intraocular pressure if some of the polymer leaks out of the coating. In the case of PVP, a molecular weight of 10,000 is preferred.

The coating material is formed by preparing an ophthalmically acceptable hydrophobic (meth)acrylic polymer, then purifying (if necessary or desired) the cured hydrophobic (meth)acrylic polymer via extraction in a suitable solvent, then dissolving the hydrophobic (meth)acrylic polymer and a ophthalmically acceptable hydrophilic polymer in a suitable solvent or mixture of solvents to form a coating solution. The proportion of hydrophobic (meth)acrylic polymer to hydrophilic polymer in the coating composition depends on the desired hydrated water content of the coating, the desired thickness of the coating, the selected hydrophobic (meth)acrylic and hydrophilic materials, etc. Once the desired coating thickness and water content are selected, the proportion can of hydrophobic (meth)acrylic polymer to hydrophilic polymer is determined by routine calculations and experimentation. In general, the desired water content of the hydrated coating will range from approx. 20-70% and the desired coating thickness will range from 0.5-1 µm. Typical concentrations of hydrophilic polymer in the coating material will therefore range from approx. 5 to approx. 50%, preferably from approx. 15 to approx. 30%.

The solvent or solvent mixture used to form the coating solution should be chosen to give a homogeneous coating solution. Because the coatings will be used to reduce glare, it is not necessary for the coating solution to be clear. Whether the coating solution is clear or not, the coating should be translucent to opaque after being applied to the edge of the implant and hydrated. An example of a suitable solvent mixture in the case of a 2-PEMA/2-PEA copolymer as the hydrophobic (meth)acrylic polymer and PRP as the hydrophilic polymer is a 2-pentanone/methanol mixture. In general, polar solvents such as alcohols will be suitable when the hydrophilic polymer is polyHEMA or polyglyceryl methacrylate, and ketones such as 2-pentanone or methylene chloride will be suitable when the hydrophilic polymer is polyacrylamide or PVP.

The coating material is preferably attached to the substrate IOL by means of one or both of the following: (1) hydrophobic or "physical" (ie, non-covalent) cross-linking and (2) interpenetrating polymer network construction. The coating material is internally cross-linked with non-covalent cross-linking. Alternatively, the coating material may be covalently cross-linked to the IOL using a cross-linking agent.

The coating solution is applied to the edge surface of the implant by conventional techniques, such as spin or dip coating processes or casting a coating layer around a preformed rod of the optical material. Dip coating is preferred. The implant is preferably dipped at such a rate as to thereby minimize any swelling of the implant caused by the solvent in the coating solution.

After the coating has been applied to the implant, the coating is dried. A two-stage drying process is preferred. First, the coated implant is allowed to dry in air until most or all of the solvent has evaporated (generally 15 minutes). The coated implant is then oven-dried at an elevated temperature, approx. 40-100 °C, to eliminate as much as possible of the remaining solvent. A preferred drying process involves air drying at room temperature for 15 minutes, followed by oven drying at 90 °C for approx. 20-60 minutes. If a covalent cross-linking agent is added to the coating solution, the coating is dried in a way that fully activates the cross-linking agent.

The coating can be easily removed with a variety of organic solvents or solvent mixtures, including the same solvent used as the base in the preparation of the coating solution. However, the coating cannot be removed by water.

Implants suitable for coating with the hydrophilic coatings of the present invention are preferably made of hydrophobic (meth)acrylic materials, but can also be constructed of silicon or silicon (meth)acrylic copolymers. Preferred hydrophobic (meth)acrylic materials are the polymeric materials described in U.S. Patent Nos. 5,290,892 and 5,693,095, the entire contents of which are hereby incorporated by reference. In the case where the implant is an IOL, the coatings of the present invention may be used with substrate materials intended for use as a "hard" IOL (inserted in an extended state) or a "collapsible" or "soft" IOL (inserted in a folded or compressed state). Suitable IOL materials to be coated include those disclosed in U.S. Patent Nos. 5,693,095 or 5,331,073. As used herein, "implants" include contact lenses.

When covalent cross-linking agents are used, it may be necessary or desirable to prepare the surface of the implant that will receive the coating by exposing the surface of the implant to a reactive plasma gas before applying the coating solution. Suitable reactive plasma gases include oxidizing gases, such as oxygen gas. A suitable plasma chamber is the P<2>CIM B-Series plasma chamber made by Advanced Plasma Systems, Inc. Using such a chamber, suitable plasma parameters include: power = 400 W, plasma gas = oxygen; pressure of plasma gas = 225 mTorr; exposure time = 4-6 minutes.

The following examples are intended to be illustrative, but not limiting.

Example 1: Mixture of hydrophobic (meth)acrylic polymer and hydrophilic polymer.

A copolymer of 2-PEMA (1.5 parts by weight) and 2-PEA (3.24 parts by weight) was prepared using Darocur 4265 (0.06 parts by weight) as an initiator. The copolymer was cured in polypropylene sheet molds (10 mm x 20 mm x 0.9 mm) by exposure to blue light for one hour using a Kulzer Palatray CU blue light unit (12-14 mW/cm 2 ). The cured copolymer (0.8345

g) was then extracted in methanol at room temperature overnight. The extracted copolymer was dried in air but not stripped of methanol solvent. Once dry, the plates were dissolved in a mixture of 2-pentanone and methanol to form the following coating solution:

Separately, a copolymer comprising 65% 2-PEA; 30% 2-PEMA; 1.8% o-methallyl Tinuvin P; and 3.2% 1,4-butanediol diacrylate prepared using 1.8% Perkadox-16 as a thermal initiator. This copolymer ("substrate copolymer") was cured in the same plates described above and then extracted in acetone (overnight, then dried in air for about 2 hours, then dried at 100°C for about 2 hours). Also, commercially available ACRYSOF<*>IOLs were obtained. The plates and IOLs were then dipped in the coating solution, air dried for approximately 5-10 minutes, and then oven dried at 90°C for 20-90 minutes. The cured coating was optically clear. After hydration of the coating, the coating is translucent/opaque due to the heterogeneous distribution of water within the coating composition. The coating thickness was typically 0.5 to 1 micron. After being hydrated for 9 months, the haze or opacity of the coating did not appear to have decreased and remained bonded to the substrate plate or IOL.

Example 2: Water content in the coating material from example 1.

In order to determine the water content of the hydrated coating material used in example 1, a multilayer film of the coating solution defined in claim 1 was cast in a polypropylene sheet mold. After each layer was applied, it was allowed to dry at room temperature in air before the next layer was added. After four or 5 layers were made, the multilayer film was dried at 100 °C for one hour. The dried film was weighed and then placed in deionized water at room temperature. The film's weight change was monitored over time. The results are shown in table 1 below. After 184 hours of hydration, the film was removed from the deionized water, weighed, extracted, dried and weighed again. The film yielded 5.7% (based on weight) extractables and had a water content (hydrated) of 52.6% (weight). The film was placed back into the deionized water for an additional 432 hours (616 hours total hydration time from the beginning of the experiment). The calculated water content at 616 hours was 59.5% (weight).

Example 3: (Comparative example) Copolymer of hydrophobic (meth)acrylic monomers and hydrophilic monomer.

To 3.25 g of 2-PEA, 1.5 g of 2-PEMA, 1.81 g of N-vinylpyrrolidone and 0.06 g of Darocur 4265 were added. The pyrrolidone content of the coating material was the same as that used in the coating material in Example 1 [27.3%: 0.33/(0.88+0.33) = 1.81/(3.25 + 1.5 + 1 .81 + 0.06)]. The resulting coating material was cured in the same polypropylene sheet molds described in Example 1. A one hour blue light cure was performed using the Palatray CU unit with a flux of 12-14mW/cm<2>. A resulting copolymer was dissolved in 2-pentanone to give coating solution with a 6% by weight copolymer content.

A pre-extracted (acetone) plate of the substrate copolymer from Example 1 was dipped in the coating solution, air dried at room temperature for 10 minutes and oven cured at 90°C for 75 minutes. The coated plate was placed in deionized water and its hydration properties followed over time. The results are shown in table 2 below.

Water content after 425 hours = 12.3% (final hydrated weight - final dried weight)/final hydrated weight Aqueous extractables = 0.6%

As shown in Tables 1 and 2, Examples 1 and 3 gave significantly different results. The hydrated PEMA-PVP polymer blend coating material is opaque and has a high water content, while the hydrated random PEMA-NVP copolymer is clear and has a lower water uptake.

The invention has been described with reference to these preferred embodiments; however, it is to be understood that it may be designed in other specific forms or variations thereof without departing from its spirit or essential characteristics. The embodiments described above are therefore considered to be illustrative in all respects and not limiting, the scope of the invention being indicated by the appended claims rather than by the preceding description.

Claims (19)

1. Method for reducing edge glare in an implantable ophthalmic lens having an optical edge surface comprising the step of applying a hydrophilic coating material to the optical edge surface wherein the coating material comprises an ophthalmically acceptable hydrophobic (meth)acrylic polymer and an ophthalmically acceptable hydrophilic polymer in an amount sufficient to reducing or eliminating edge glare when the coating material is hydrated, and wherein the coating material has a Tg of less than 37°C when hydrated. 2. Method according to claim 1, in which the hydrophilic polymer is selected from the group consisting of polyhydroxyethyl methacrylate; polyacrylamide; polyglyceryl methacrylate and polyvinylpyrrolidone. 3. Method according to claim 2, in which the hydrophilic polymer is polyvinyl pyrrolidone. 4. Method follows claim 1, in which the hydrophilic polymer has a weight average molecular weight in the range 2,500 - 100,000. 5. Method according to claim 4, in which the hydrophilic polymer is polyvinyl pyrrolidone which has a weight average molecular weight of 10,000. 6. Method according to claim 1, in which the amount of the hydrophilic polymer in the coating material is approx. 5 - 50% (weight). 7. Method according to claim 1, in which the coating material has a hydrated water content of approx. 20 - 70%. 8. Method according to claim 1, in which the hydrophobic (meth)acrylic polymer comprises a monomer with the formula in which: X is H or CH3; m is 0-6; Y is nothing, 0, S or NR, wherein R is H, CH3/Cn H2n+ i (n=1-10), iso-OC3 H7 , C6 H5 or CH2 C6 H5 ; and Ar is any aromatic ring which may be unsubstituted or substituted with CH3 , C2 H5 , n-C3 H7 , iso-C3 H7 , OCH3 , C6 Hn , Cl, Br, C5 H5 or CH2 C6 H5 . 9. A hydrophilic coating material for a surgical implant wherein the coating material comprises an ophthalmically acceptable hydrophobic (meth)acrylic polymer and an ophthalmically acceptable hydrophilic polymer, and wherein the coating material has a Tg of less than 37°C when hydrated. 10. The coating material according to claim 9, in which the hydrophilic polymer is selected from the group consisting of polyhydroxyethyl methacrylate; polyacrylamide; polyglyceryl methacrylate and polyvinyl pyrrolidone. 11. The coating material according to claim 9, wherein the hydrophilic polymer is polyvinyl pyrrolidone. 12. The coating material according to claim 9, wherein the hydrophilic polymer has a weight average molecular weight in the range 2,500 - 100,000. 13. The coating material according to claim 12, wherein the hydrophilic polymer is polyvinyl pyrrolidone which has a weight average molecular weight of 10,000. 14. The coating material according to claim 9, in which the amount of the hydrophilic polymer in the coating material is approx. 5 - 50% (weight). 15. The coating material according to claim 14, wherein the amount of the hydrophilic polymer in the coating material is approx. 15 - 30% (weight) . 16. The coating material according to claim 9, in which the coating material has a hydrated water content of approx. 2 0 - 70%. 17. The coating material according to claim 9, wherein the hydrophobic (meth)acrylic polymer comprises a monomer with the formula wherein: X is H or CH 3 ; m is 0-6; Y is nothing, O, S or NR, wherein R is H, CH3 , Cn H2n+ i (n=1-10), iso-OC3 H7 , C6 H5 or CH2 C6 H5 ; and Ar is any aromatic ring which may be unsubstituted or substituted with CH3 , C2 H5 , n-C3 H7 , iso-C3 H7 , OCH3 , C6 Hn , Cl, Br, C6 H5 or CH2 C6 H5 . 18. The coating material according to claim 17, wherein the hydrophobic (meth)acrylic polymer comprises a monomer selected from the group consisting of 2-phenylethyl acrylate and 2-phenylethyl methacrylate. 19. The coating material according to claim 9, in which the hydrophobic (meth)acrylic polymer optionally comprises one or more ingredients selected from the group consisting of UV absorbers; blue light blocking dyes; and chain transfer agents.