JP2003519538A - Implantable ophthalmic lens coating to reduce edge glare - Google Patents

Abstract

  (57) [Summary] The present invention relates to hydrophilic coating compositions for surgical implantation, in particular ophthalmic implants comprising silicone or hydrophobic (meth) acrylic materials. More specifically, 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 an implantable ophthalmic lens. The method includes applying a coating comprising an ophthalmically acceptable hydrophobic (meth) acrylic polymer and an ophthalmically acceptable hydrophilic polymer to the ocular marginal surface of the implant. When hydrated, the coating is hazy or opaque and reduces or eliminates edge glare.

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to coatings for implantable ophthalmic lenses. Specifically, the present invention relates to hydrophobic coatings applied to the edges of implantable ophthalmic lenses.

BACKGROUND OF THE INVENTION Rigid, collapsible and implantable ophthalmic lens materials are known. The most common rigid material used in eye transplants is polymethylmethacrylate (“PM
MA). Collapsible intraocular lens (“IOL”) materials are commonly 3
Two categories (silicone materials, hydrogel materials, and non-hydrogels (“hydrophobic”)
) (Meth) acrylic material)). For example, Foldable In
traocular Lenses, Ed. Martin et al., Slack In
corporated, Thorofare, New Jersey (1993)
)checking. For purposes of this application, a hydrophobic (meth) acrylic material is a (meth) acrylic material that absorbs less than about 5% water at room temperature.

As described in US Pat. No. 5,755,786, IOLs (particularly IOLs designed for implantation through small incisions) may suffer from edge glare problems. The invention described in the '786 patent provides multiple v-shaped groove-like means on the edge surface of the eye to reflect visible light that contacts the edge surface away from the patient's retina. Reduces glare on the edges.

Another method of reducing edge glare is US Pat. No. 5,693,09
No. 3, No. 5,769,889; No. 4,808,181; and No. 4,
605,409.

SUMMARY OF THE INVENTION The present invention relates to hydrophilic coating compositions for surgical implantation, particularly ophthalmic implants comprising silicone or hydrophobic (meth) acrylic materials. More specifically, the present invention relates to coating materials 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 an implantable ophthalmic lens. The method involves applying to the ocular marginal surface of the implant a coating comprising an ophthalmically acceptable hydrophobic (meth) acrylic polymer and an ophthalmically acceptable hydrophilic polymer. When hydrated, the coating is hazy or opaque and reduces or eliminates edge glare.

[0007]   (Detailed Description of the Invention)   Unless otherwise indicated, all amounts are expressed as weight percent.

As used herein, “hydrophobic (meth) acrylic polymer” refers to a hydrophobic methacrylic polymer, a hydrophobic acrylic polymer, or a hydrophobic copolymer containing both methacrylic and acrylic functional groups. Means As used herein, "hydrophobic" means a material that absorbs 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 hydrated, the coating material should be
It has a T _g of less than 37 ° C., and preferably less than 15 ° C. The hydrophobic (meth) acrylic polymer component in the coating material is preferably tacky and helps adhere the coating material to the base layer. Many ophthalmically acceptable hydrophobic (meth) acrylic polymers are known and are described in US Pat. No. 5,290,8.
92; 5,693,095; and 5,331,073, the entire contents of which are incorporated herein by reference. Although aliphatic (meth) acrylate monomers can be used to form hydrophobic (meth) acrylic polymers, the hydrophobic (meth) acrylic polymers are preferably:

[0010]

[Chemical 3] Containing an aromatic group, such as the materials defined in US Pat. No. 5,693,095,
Comprising at least one (meth) acrylic monomer, Where: X is H or CH_ThreeAnd   m is 0-6;   Y is absent, O, S, or NR, where R is H, CH_Three , C_nH_{2n + 1}(N = 1 to 10), iso-OC_ThreeH₇, C₆H₅Or CH _Two C₆H₅And; and   Ar cannot be substituted or CH_Three, C_TwoH₅, N-C_ThreeH₇, Iso-
OC_ThreeH₇, OCH_Three, C₆H₁₁, Cl, Br, C₆H₅Or CH_TwoC₆H ₅ Is any aromatic ring that may be substituted with. Suitable hydrophobic (meth) acrylic polymers include 2-phenylethylmethacryl.
Relate (2-PEMA) and 2-phenylethyl acrylate (2-PEA)
).

After selection of the (meth) acrylic monomer, an initiator (generally about 2% or less) is used to form a hydrophilic (meth) acrylic polymer. Any type of polymerization initiator can be used, including thermal and photoinitiators. A preferred initiator is the benzoylphosphine oxide initiator (2,4,6-trimethyl-benzoyldiphenylphosphine oxide (“TPO”)), which can be activated by blue light or UV irradiation. Initiators include conventional peroxides (t-butyl peroctoate and bis-azoisobutronitrile) Suitable UV initiators include benzoin methyl ether, Darocur 1173.
UV initiators and Darocur 4265 UV initiators.

The hydrophobic (meth) acrylic polymer is a UV absorber which is optionally copolymerizable with other (meth) acrylic components; blue light which is copolymerizable with other (meth) acrylic components. A blocking colorant; and one or more components selected from the group consisting of chain transfer agents to minimize cross-linking.

The UV absorbing chromophore can be any compound that absorbs light having a wavelength shorter than about 400 nm, but does not absorb any substantial amount of visible light. Suitable copolymerizable UV absorbing compounds are the substituted 2-hydroxybenzophenones disclosed in US Pat. No. 4,304,895, and the 2-hydroxy-benzophenones disclosed in US Pat. No. 4,582,311. It is 5-acryloxyphenyl-2H-benzotriazole. The most preferred ultraviolet absorbing compound is 2- (3'-methallyl-2 '
-Hydroxy-5'-methylphenyl) benzotriazole. Suitable polymerizable blue light blocking chromophores include the chromophores disclosed in US Pat. No. 5,470,932. When a blue light activated polymerizable initiator is selected and a blue light blocking colorant is added, the identity or amount of this polymerization initiator is adjusted to minimize any interference. obtain.

Chain transfer agents, if present, are typically added in amounts ranging from 0.01 to 0.4%. Many chain transfer agents are known in the art. Examples of suitable chain transfer agents include 1-dodecaneethiol and 2-mercaptoethanol.

The hydrophilic polymer included in the coating material of the present invention can be any ophthalmically acceptable hydrophilic polymer. Suitable hydrophilic polymers include, but are not limited to, polyhydroxyethylmethacrylate (polyHEMA); polyacrylamide; polyglycerylmethacrylate and polyvinylpyrrolidone (PVP). The most preferred hydrophilic polymer is PVP. These hydrophilic polymers are either commercially available or can be made using known methods, and are preferably obtained in purified form to minimize extractables upon implantation of the coated IOL.

The hydrophilic polymer has a molecular weight (average molecular weight) in the range of 2,500 to 100,000. It is important that the molecular weight of the hydrophilic polymer is large enough to form the hydrophobic domains that can scatter light, and therefore is present in the hydrogel coating material in an amount sufficient. The hydrophilic polymer should not be too small,
Otherwise, it may leach from the coating after it is applied to the IOL. The hydrophilic polymer should not be too large, otherwise some of the polymer may affect intraocular pressure in the event of leaching from the coating. For PVP, a molecular weight of 10,000 is preferred.

The coating material is prepared by preparing an ophthalmically acceptable hydrophobic (meth) acrylic polymer and then (if necessary or desired) cured hydrophobic via extraction in a suitable solvent. By purifying the (meth) acrylic polymer and then dissolving the hydrophobic (meth) acrylic polymer and the ophthalmically acceptable hydrophilic polymer in a suitable solvent or mixture of solvents to form a coating solution. It is formed. The ratio of hydrophobic (meth) acrylic polymer to hydrophilic polymer in the coating composition depends on the desired hydrated water content for the coating,
It depends on the desired thickness of the coating, the hydrophobic (meth) acrylic and hydrophobic materials selected, and the like. Once the desired coating thickness and water content are selected, the ratio of hydrophobic (meth) acrylic polymer to hydrophilic polymer is:
It can be determined by routine calculations and experiments. Generally, the desired water content of the hydrated coating is in the range of about 20-70%, and the desired coating thickness is in the range of 0.5-1 μm. Thus, a typical concentration of hydrophilic polymer in the coating material is in the range of about 5 to about 50%, preferably about 15 to about 30%.

The solvent or solvent mixture used to form the coating solution should be selected to give a homogeneous coating solution. It is not necessary for the coating solution to be transparent, as the coating is used to reduce glare. Whether the coating solution is clear or not, the coating should be translucent to opaque after being applied to the implant edges and hydrated. 2-PEMA / 2-P as hydrophobic (meth) acrylic polymer
An example of a suitable solvent mixture in the case of EA copolymer and PVP as the hydrophilic polymer is a 2-pentanone / methanol mixture. Generally, when the hydrophilic polymer is poly HEMA or polyglyceryl methacrylate, a polar solvent (
For example, alcohol) is suitable, and when the hydrophobic polymer is polyacrylamide or PVP, a ketone (eg 2-pentanone) or methylene chloride is suitable.

The coating material is preferably: (1) hydrophobic or “physical” (ie non-covalent) crosslinks, and (2) interpenetrated with each other.
attached to the substrate IOL by one or both means. The coating material is internally crosslinked by non-covalent crosslinking. Alternatively, the coating material may be covalently crosslinked to the IOL with a crosslinker.

The coating solution may be applied to the edge surface of the implant by conventional techniques such as spin coating or dip coating processes, or casting a coating layer around a preformed rod of ophthalmic material. Applied to. Dip coating is preferred. The implant is preferably immersed at a rate that minimizes any swelling of the implant caused by the solvent in the coating solution.

After the coating is applied to the implant, the coating is dried. Two
A staged drying process is preferred. First, the coated implant
Dry in air (usually 15 minutes or less) until most or all of the solvent has evaporated. Secondly, the coated implant is exposed to high temperatures (about 40-
Bake at 100 ° C.) to remove as much residual solvent as possible. A preferred drying process is to air dry at room temperature for 15 minutes at room temperature, followed by about 20-6 at 90 ° C.
Including a 0 minute baking step. When a covalent crosslinker is added to the coating solution, the coating is dried in a manner that fully activates the crosslinker.

The coating can be easily removed by various organic solvents or solvent mixtures and contains 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 coating of the present invention are preferably made from hydrophobic (meth) acrylic materials, but may also be constructed from silicone or silicone- (meth) acrylic copolymers. . Preferred hydrophobic (meth) acrylic materials are US Pat. Nos. 5,290,892 and 5,6.
93,095, all of which are hereby incorporated by reference herein. If the implant is an IOL, the coating of the present invention may be either a "hard" IOL (which is inserted unfolded) or a "foldable" or "soft" IOL (which may be folded or unfolded). , Or inserted in the compressed state) and may be used in combination with a base material intended for use. Suitable IOL materials to be coated include those disclosed in US Pat. Nos. 5,693,095 or 5,331,073. As used herein, "implant" includes contact lenses.

If covalent crosslinkers are used, it is necessary or desirable to prepare the surface of the implant to be coated by exposing the surface of the implant to a reactive plasma gas prior to applying the coating solution. Suitable reactive plasma gases include oxidizing gases such as oxygen gas. Suitable plasma chambers are available from Advanced Plasma Systems, Inc. A ^P 2 CIM B-Series plasma chamber made by. Suitable plasma parameters using such a chamber include: power = 400 W; plasma gas = oxygen; plasma gas pressure = 225 mT.
oor; exposure time = 4-6 minutes.

[0025]   The following examples are intended to be illustrative but not limiting.

Example 1 Mixture of Hydrophobic (Meth) Acrylic Polymer and Hydrophilic Polymer Copolymer of 2-PEMA (1.5 parts by weight) and 2-PEA (3.24 parts by weight) was added to Darocur 4265. (0.06 parts by weight) was used as the initiator. The copolymer was cured in a polypropylene slab mold (10 mm x 20 mm x 0.9 mm) by exposing it to blue light for 1 hour using a Kulzer Palatray CU blue light unit (12-14 mW / cm ² ). The cured copolymer (0.8345g) was then added to methanol in
Extract overnight at room temperature. The extracted copolymer was dried in air but the methanol solvent was not removed. Once dried, this slab is dissolved in a mixture of 2-pentanone and methanol to form the following coating solution:

[0027]

[Chemical 4] Separately, 2-PEA 65%; 2-PEMA 30%; o-methallyl Tinuv
in P 1.8%; and 1,4-butanediol diacrylate 3.2%.
Was prepared using 1.8% Perkadox-16 as the thermal initiator. This copolymer ("Substrate Copolymer")
Was cured in the same slab mold as above and then extracted in acetone (overnight,
Then, dried in air for about 2 hours and then at 100 ° C. for about 2 hours)
. In addition, a commercially available ACRYSOF (registered trademark) IOL was obtained. The slab and IOL are then dipped into the coating solution and dried in air for about 5-10 minutes,
Then, it was baked at 90 ° C. for 20 to 90 minutes. The cured coating was optically clear. Upon 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 kept hydrated for 9 months, the haze or opacity of the coating did not appear to have decreased and remained attached to the base slab or IOL.

Example 2: Water content of the coating material of Example 1 To determine the water content of the hydrated coating material used in Example 1, a multilayer film of the coating solution defined in Example 1 Was cast into a polypropylene slab mold. After applying each layer, it was dried at room temperature in air before adding the next layer. After 4 or 5 layers have been produced, the multilayer film is heated to 100 ° C.
And dried for 1 hour. The dry film was weighed and then placed in deionized water at room temperature. The change in weight of this film was monitored over time. The result
The results are shown in Table 1 below. After 184 hours of hydration, the film was removed from deionized water, weighed, extracted, dried and reweighed. This film is 5
． It was 7% by weight extractable and had a water content of 52.6% by weight (hydrated). The film was placed in deionized water for a further 432 hours (total hydration time of 616 hours from the start of the experiment). The water content calculated at 616 hours was 59.5% (by weight).

[0029]

[Table 1] Example 3: (Comparative Experiment) Hydrophobic (meth) acrylic monomer and hydrophilic monomer copolymer) To 3.25 grams of 2-PEA, 1.50 grams of 2-PEMA, 1.81 grams of N-vinylpyrrolidone. , And 0.06 grams of Darocur 4265 were added. The "pyrrolidone" content in the coating material was the same as that used in the coating material of Example 1 (27.3%: 0.33 / (0.8
8 + 0.33) = 1.81 / (3.25 + 1.5 + 1.81 + 0.06)). The resulting coating material was cured in the same polypropylene slab mold described in Example 1. Curing of blue light was performed for 1 hour using a Palatray CU unit with a luminous flux of 12-14 mW / cm ² . The resulting copolymer was converted to 2
Dissolved in pentanone to give a coating solution with a copolymer content of 6% by weight.

A pre-extracted Substrate Copolymer (acetone) slab of Example 1 was immersed in this coating solution and air dried at room temperature for 10 minutes,
Then, it was cured in an oven at 90 ° C. for 75 minutes. The coated slab,
It was placed in deionized water and its hydration properties followed over time. The results are shown in Table 2 below.

[0031]

[Table 2] Water content after 425 hours = 12.3% (final hydrated weight-final dry weight)
/ Final hydrated weight Aqueous extract = 0.6%.

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

The present invention has been described with reference to certain preferred embodiments; however, the present invention is not limited to other specific forms or modifications thereof without departing from the spirit or essential characteristics of the invention. It should be understood that it can be implemented. Accordingly, the above embodiments, in all respects, are considered to be illustrative, but not limiting, the scope of the invention being indicated by the appended claims rather than the foregoing description.

Claims (19)

[Claims] 1. A method for reducing edge glare in an implantable ophthalmic lens having an eye edge surface, the method comprising applying a hydrophilic coating material to the eye edge surface. Wherein the coating material comprises an ophthalmically-acceptable hydrophobic (meth) acrylic polymer and an ophthalmically-acceptable hydrophilic polymer on the edges when the coating material is hydrated. The method, comprising in an amount sufficient to reduce or eliminate glare, and the coating has a T _g of less than 37 ° C. when hydrated. 2. The method of claim 1, wherein the hydrophilic polymer is selected from the group consisting of polyhydroxyethylmethacrylate; polyacrylamide; polyglycerylmethacrylate and polyvinylpyrrolidone. 3. The method according to claim 2, wherein the hydrophilic polymer is polyvinylpyrrolidone. 4. The method of claim 1, wherein the hydrophilic polymer has a weight average molecular weight in the range of 2,500 to 100,000. 5. The method of claim 4, wherein the hydrophilic polymer is polyvinylpyrrolidone having a weight average molecular weight of 10,000. 6. The amount of the hydrophilic polymer in the coating material is
The method of claim 1, wherein the method is about 5-50% by weight. 7. The method of claim 1, wherein the coating material has a hydrated water content of about 20-70%. 8. The hydrophobic (meth) acrylic polymer has the formula: [Chemical 1] Containing the monomer of Where: X is H or CH_ThreeAnd   m is 1 to 6;   Y is absent, O, S, or NR, where R is H, CH_Three , C_nH_{2n + 1}(N = 1 to 10), iso-OC_ThreeH₇, C₆H₅Or CH _Two C₆H₅And; and   Ar cannot be substituted or CH_Three, C_TwoH₅, N-C_ThreeH₇, Iso-
OC_ThreeH₇, OCH_Three, C₆H₁₁, Cl, Br, C₆H₅Or CH_TwoC₆H ₅ Is any aromatic ring that can be substituted with The method of claim 1. 9. A surgical implant comprising a hydrophilic coating, wherein the coating comprises an ophthalmically acceptable hydrophobic (meth) acrylic polymer and an ophthalmically acceptable hydrophilic polymer. , And the coating material, when hydrated, has a T _g of less than 37 ° C. 10. The surgical implant according to claim 9, wherein the hydrophilic polymer is selected from the group consisting of polyhydroxyethyl methacrylate; polyacrylamide; polyglyceryl methacrylate and polyvinylpyrrolidone. 11. The surgical implant according to claim 9, wherein the hydrophilic polymer is polyvinylpyrrolidone. 12. The surgical implant according to claim 9, wherein the hydrophilic polymer has a weight average molecular weight in the range of 2,500 to 100,000. 13. The surgical implant of claim 12, wherein the hydrophilic polymer is polyvinylpyrrolidone having a weight average molecular weight of 10,000. 14. The surgical implant of claim 9, wherein the amount of hydrophilic polymer in the coating material is about 5-50% by weight. 15. The surgical implant of claim 14, wherein the amount of hydrophilic polymer in the coating material is about 15-30% by weight. 16. The surgical implant of claim 9, wherein the coating material has a hydrated water content of about 20-70% by weight. 17. The surgical implant according to claim 9, wherein:
The hydrophobic (meth) acrylic polymer has the formula: [Chemical 2] Containing the monomer of Where: X is H or CH_ThreeAnd   m is 1 to 6;   Y is absent, O, S, or NR, where R is H, CH_Three , C_nH_{2n + 1}(N = 1 to 10), iso-OC_ThreeH₇, C₆H₅Or CH _Two C₆H₅And; and   Ar cannot be substituted or CH_Three, C_TwoH₅, N-C_ThreeH₇, Iso-
OC_ThreeH₇, OCH_Three, C₆H₁₁, Cl, Br, C₆H₅Or CH_TwoC₆H ₅ Is any aromatic ring that can be substituted with Surgical implant. 18. The surgical implant 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 hydrophobic (meth) acrylic polymer optionally comprises one or more components selected from the group consisting of UV absorbers; blue light blocking colorants; and chain transfer agents. The surgical implant according to claim 9.