Note: Descriptions are shown in the official language in which they were submitted.
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COATING OF IMPLANTABLE OPHTHALMIC LENSES TO REDUCE EDGE GLARE
FIELD OF THE INVENTION
This invention relates to coatings for implantable ophthalmic lenses. In
particular, the present invention relates to hydrophilic coatings that are
applied
to the edge of implantable ophthalmic lenses.
,o
BACKGROUND OF THE INVENTION
Both rigid and foldable implantable ophthalmic lens materials are
known. The most common rigid material used in ophthalmic implants is
,5 polymethyl methacrylate ("PMMA"). Foldable intraocular lens ("IOL")
materials can generally be divided into three categories: silicone 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 of the present
2o application, hydrophobic (meth)acrylic materials are (meth)acrylic
materials
that absorb less than approximately 5% water at room temperature.
As described in U.S. Patent No. 5,755,786, IOLs, particularly IOLs
designed for implantation through a small incision, can suffer from a problem
of
25 edge glare. The invention described in the '786 patent reduces edge glare
by
including means, such as a plurality of v-shaped grooves, on the optic edge's
surface for reflecting visible light that contacts the edge surface away from
the
retina of the patient.
3o Other methods of reducing edge glare include those described in U.S.
Patent Nos. 5,693,093; 5,769,889; 4,808,181; and 4,605,409.
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SUMMARY OF THE INVENTION
The present invention relates to hydrophilic coating compositions for
surgical implants, particularly 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.
,0 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 optic
edge surface. When hydrated, the coating is hazy or opaque and reduces or
,5 eliminates edge glare.
DETAILED DESCRIPTION OF THE INVENTION
Unless indicated otherwise, 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 copolymer containing both methacrylic and acrylic functional
groups. As used herein, "hydrophobic" means the materials absorb less than
approximately 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 has a T9 less than 37 °C,
and
preferably less than 15 °C. The hydrophobic (meth)acrylic polymer
ingredient
in the coating material is preferably tacky to aid in attaching the coating
material
to the substrate. Many ophthalmically acceptable hydrophobic (meth)acrylic
polymers are known, including those described in U.S. Patent Nos. 5,290,892;
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5,693,095; and 5,331,073, the entire contents of which are hereby incorporated
by reference. Although aliphatic (meth)acrylate monomers can be used to form
the hydrophobic (meth)acrylic polymer, the hydrophobic (meth)acrylate polymer
preferably comprises at least one (meth)acrylic monomer that contains an
aromatic group, such as those materials defined in US 5,693,095:
X
CH2 = C - COO-(CH2)m-Y-Ar
,o
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, CgHS, or CH2C6H5; and
,5 Ar is any aromatic ring which can be unsubstituted or substituted
with CH3, C2H5, n-C3H7, iso-C3H7, OCH3, CgH 11, CI, Br, CgHS,
or CH2C6H5.
Suitable hydrophobic (meth)acrylic polymers include copolymers of 2-
2o phenylethyl methacrylate (2-PEMA) and 2-phenylethyl acrylate (2-PEA).
After selecting the (meth)acrylic monomer(s), the hydrophobic
(meth)acrylic polymer is formed using an initiator (generally about 2% or
less).
Any type of polymerization initiator may be used, including thermal initiators
and
25 photoinitiators. A preferred initiator is the benzoylphosphine oxide
initiator,
2,4,6-trimethyl-benzoyldiphenylophosphine oxide ("TPO"), which can be
activated by blue light or UV irradiation. Suitable thermal initiators include
the
conventional peroxides t-butyl peroctoate and bis-azoisobutronitrile. Suitable
UV initiators include benzoin methyl ether, Darocur 1173, and Darocur 4265 UV
3o initiators.
The hydrophobic (meth)acrylic polymer optionally contains one or more
ingredients selected from the group consisting of UV absorbers that are
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copolymerizable with the other (meth)acrylic ingredients; blue-light blocking
colorants that are copolymerizable with the other (meth)acrylic ingredients;
and chain transfer agents to minimize cross-linking.
Ultraviolet absorbing chromophores can be any compound which
absorbs light having a wavelength shorter than about 400 nm, but does not
absorb any substantial amount 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-
,o 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'-methyl phenyl) 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 chosen and a
blue-
,5 light blocking colorant is added, the polymerization initiator identity or
concentration may have 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.
2o Examples of suitable chain transfer agents include 1-dodecanethiol and 2-
mercaptoethanol.
The hydrophilic polymer contained in the coating materials of the present
invention may be any ophthalmically acceptable hydrophilic polymer. Suitable
25 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 in order to
3o minimize extractables upon implantation of the coated IOL.
The hydrophilic polymer preferably has a molecular weight (weight avg.)
in the range of 2,500 - 100,000. It is important that the hydrophilic
polymer's
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molecular weight be great enough and be present in the hydrogel coating
material in a sufficient amount to form hydrophilic domains capable of
dispersing light. The hydrophilic polymer should not be too small, otherwise
an
appreciable amount of it may leach 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 in the event that some of the polymer
leaches
out of the coating. In the case of PVP, a molecular weight of 10,000 is
preferred.
,o 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 an
ophthalmically acceptable hydrophilic polymer in a suitable solvent or mixture
of
,5 solvents to form a coating solution. The proportion of hydrophobic
(meth)acrylic
polymer to hydrophilic polymer in the coating composition depends upon on the
desired hydrated water content for the coating, the desired thickness of the
coating, the chosen hydrophobic (meth)acrylic and hydrophilic materials, etc.
Once the desired coating thickness and water content are chosen, the
Zo proportion of hydrophobic (meth)acrylic polymer to hydrophilic polymer can
be
determined by routine calculations and experimentation. In general, the
desired water content of the hydrated coating will range from about 20 - 70%
and the desired coating thickness will range from 0.5 - 1 Vim. Typical
concentrations of hydrophilic polymer in the coating material will therefore
25 range from about 5 to about 50%, preferably from about 15 to about 30%.
The solvent or solvent mixture used to form the coating solution should
be chose 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.
3o Whether or not the coating solution is clear, the coating should be
translucent
to opaque after being applied to the implant's edge 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 PVP as the hydrophilic polymer is a 2-
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pentanone/methanol mixture. In general, polar solvents such as alcohols will
be suitable when the hydrophilic polymer is polyHEMA or
polyglycerylmethacrylate, 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" (i.e.,
non-
covalent) cross-linking and (2) interpenetrating polymer networking. The
,o coating material is internally cross-linked by non-covalent cross-linking.
Alternatively, the coating material may be covalently cross-linked to the IOL
by
means of a cross-linking agent.
The coating solution is applied to the implant's edge surface by
,s conventional techniques, such as spin- or dip-coating processes or casting
a
coating layer around a pre-formed rod of the optic material. Dip-coating is
preferred. The implant is preferably dipped at such a rate so as to minimize
any swelling of the implant caused by the solvent in the coating solution.
2o After the coating is 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).
Second, the coated implant is baked at elevated temperature, about 40 - 100
°C, to eliminate as much of the remaining solvent as possible. A
preferred
25 drying process involves room temperature air drying for 15 minutes,
followed by
baking at 90 °C for about 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.
3o The coating can be easily removed by a variety of organic solvents or
solvent mixtures, including the same solvent used as the base in the
preparation of the coating solution. The coating cannot be removed by water,
however.
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The implants suitable for coating with the hydrophilic coatings of the
present invention are preferably made of hydrophobic (meth)acrylic materials,
but could also be constructed of silicone or silicone-(meth)acrylic
copolymers.
Preferred hydrophobic (meth)acrylic materials are those 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 in conjunction with
substrate materials intended for use as a "hard" IOL (that is inserted in an
,o unfolded state) or a "foldable" or "soft" IOL (that is 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" includes contact lenses.
,5 When covalent cross-linking agents are used, it may be necessary or
desirable to prepare the implant's surface that will receive the coating by
exposing the implant's surface to a reactive plasma gas prior to applying the
coating solution. Suitable reactive plasma gases include oxidizing gases, such
as oxygen gas. A suitable plasma chamber is the P2CIM B-Series plasma
Zo chamber made by Advanced Plasma Systems, Inc. Using such a chamber,
suitable plasma parameters include: power = 400 W, plasma gas = oxygen;
pressure of the 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.
3o The copolymer was cured in polypropylene slab 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/cm2). The cured copolymer (0.8345 g) was then
extracted in methanol at room temperature overnight. The extracted copolymer
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was dried in air, but not stripped of methanol solvent. Once dry, the slabs
were
dissolved in a mixture of 2-pentanone and methanol to form the following
coating solution:
Ingredient amount (parts by weight)
2-PEMA/2-PEA copolymer 0.88
PVP (10,000 MW) 0.33
Methanol 1.38
2-Pentanone 12.46
,o
Separately, a copolymer comprising 65% 2-PEA; 30% 2-PEMA; 1.8% o-
methallyl Tinuvin P; and 3.2% 1,4-butanediol diacrylate was prepared using
1.8% Perkadox-16 as a thermal initiator. This copolymer ("Substrate
Copolymer"} was cured in the same slab molds described above and then
,5 extracted in acetone (overnight, then dried in air for approximately 2
hours, then
dried at 100 °C for approximately 2 hours). Also, commercially
available
ACRYSOF~ IOUs were obtained. The slabs and IOLs were then dipped in the
coating solution, dried in air for approximately 5 - 10 minutes, and then
baked
at 90 °C for 20 - 90 minutes. The cured coating was optically clear.
After
2° hydrating the coating, the coating is translucent/opaque due to the
heterogeneous distribution of water within the coating composition. Coating
thickness was typically 0.5 to 1 microns. After remaining hydrated for 9
months, the coating's haze or opacity did not appear to have diminished and
remained attached to the substrate slab or IOL.
z5
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 multi-layer film of the coating solution defined in Example 1 was
cast in a polypropylene slab mold. After each layer was applied, it was
allowed
3o to dry at room temperature in air before the next layer was added. After
four or
five layers were made, the multi-layered film was dried at 100 °C for
one hour.
The dried film was weighed and then placed in de-ionized water at room
temperature. The film's weight change was monitored over time. The results
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are shown in Table 1 below. After 184 hours of hydration, the film was
removed from the de-ionized water, weighed, extracted, dried and weighed
again. The film gave 5.7% (by weight) extractables and had a water content
(hydrated) of 52.6% (weight). The film was replaced in 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).
Table 1
Elapsed Slab Optical % Weight Increase
Time (hrs)Weight Appearance of Slab
(g) (coating)
0 0.0475 clear 0
15.5 0.0628 opaque 24.4
40 0.0702 opaque 32.3
112 0.0840 opaque 43.4
184 0.0945 opaque 49.7
616 0.1106 opaque 57.0
,0
Example 3: (Comparative Example) Copolymer of Hydrophobic (Meth)acrylic
Monomers and Hydrophilic Monomer.
To 3.25 grams of 2-PEA, 1.50 grams 2-PEMA, 1.81 grams N
vinylpyrrolidone, and 0.06 grams of Darocur 4265 were added. The
,5 'pyrrolidone' content of the coating material was the same as that used in
the
coating material of 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 slab molds described in Example 1. A one-hour, blue-light cure
was performed using the Palatray CU unit at a flux of 12-14 mW/cm2. The
z0 resulting copolymer was dissolved in 2-pentanone to give a coating solution
with a 6 wt-% copolymer content.
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A pre-extracted (acetone) slab of the Substrate Copolymer of 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 slab was
placed
into deionized water and its hydration properties followed over time. The
results are shown in Table 2 below.
Table 2
Elapsed Slab Optical % Weight Increa
~ Time Weight Appearance of Slab
(hrs) (g)
(coating)
0 0.2060 clear 0
25 0.2151 clear 4.2
96 0.2234 clear 7.8
144 0.2263 clear 8.9
425 0.2333 clear 11.7
Water content after 425 hours = 12.3% (final hydrated weight - final
,0 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 mixture coating material is opaque
,5 and of high water content, while the hydrated, random PEMA-NVP copolymer is
clear and has a lower water uptake.
The invention has been described by reference to certain preferred
embodiments; however, it should be understood that it may be embodied in
zo 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 restrictive, the scope
of the
invention being indicated by the appended claims rather than by the foregoing
description.
