U.S. patent application number 09/766493 was filed with the patent office on 2001-09-27 for high refractive index ophthalmic device materials prepared using a post-polymerization cross-linking method.
Invention is credited to LeBoeuf, Albert R., Schlueter, Douglas C., Weinschenk, Joseph I. III.
Application Number | 20010025086 09/766493 |
Document ID | / |
Family ID | 26766077 |
Filed Date | 2001-09-27 |
United States Patent
Application |
20010025086 |
Kind Code |
A1 |
LeBoeuf, Albert R. ; et
al. |
September 27, 2001 |
High refractive index ophthalmic device materials prepared using a
post-polymerization cross-linking method
Abstract
Acrylic, high refractive index ophthalmic device materials
comprising an aryl acrylic monomer, a first stage polymerization
initiator and a second stage cross-linking agent are prepared in a
two-stage method. The monomers used to form the ophthalmic device
materials do not contain cross-linking agents having more than one
unsaturated bond. In the first stage of the method, the materials
are polymerized. In the second stage, the materials are
cross-linked by exposure to heat.
Inventors: |
LeBoeuf, Albert R.;
(Burleson, TX) ; Schlueter, Douglas C.; (Forth
Worth, TX) ; Weinschenk, Joseph I. III; (Forth Worth,
TX) |
Correspondence
Address: |
ALCON RESEARCH, LTD.
R&D COUNSEL, Q-148
6201 SOUTH FREEWAY
FORT WORTH
TX
76134-2099
US
|
Family ID: |
26766077 |
Appl. No.: |
09/766493 |
Filed: |
January 19, 2001 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
09766493 |
Jan 19, 2001 |
|
|
|
09283592 |
Apr 1, 1999 |
|
|
|
60081874 |
Apr 15, 1998 |
|
|
|
Current U.S.
Class: |
525/329.7 ;
526/319 |
Current CPC
Class: |
A61L 27/16 20130101;
C08F 220/26 20130101; G02B 1/043 20130101; A61L 2430/16 20130101;
C08F 220/12 20130101; G02B 1/043 20130101; C08L 33/06 20130101;
G02B 1/043 20130101; C08L 33/14 20130101; A61L 27/16 20130101; C08L
33/04 20130101 |
Class at
Publication: |
525/329.7 ;
526/319 |
International
Class: |
C08F 020/02; C08F
020/02 |
Claims
We claim:
1. A two-stage method for preparing an acrylic, high refractive
index ophthalmic device material, wherein the ophthalmic device
material comprises (i) at least one aryl acrylic hydrophobic
monomer of the formula 2wherein: X is H or CH.sub.3; m is0-10; Y is
nothing, O, S, or NR wherein R is H, CH.sub.3, C.sub.nH.sub.2n+1
(n=1-10) iso OC.sub.3H.sub.7, C.sub.6H.sub.5, or
CH.sub.2C.sub.6H.sub.5; Ar is any aromatic ring which can be
unsubstituted or substituted with CH.sub.3, C.sub.2H.sub.5,
n-C.sub.3H.sub.7, iso-C.sub.3H.sub.7, OCH.sub.3, C.sub.6H.sub.11,
Cl, Br, C.sub.6H.sub.5, or CH.sub.2C.sub.6H.sub.5; (ii) a first
stage polymerization initiator selected from the group consisting
of photoinitiators and thermal free radical initiators having a 10
hr t.sub.1/2 of about 55.degree. C. or less; and (iii) a second
stage cross-linking agent where the second stage cross-linking
agent is a thermal free radical initiator having a 10 hr t.sub.1/2
of about 50.degree. C. or greater if the first stage polymerization
initiator is a photoinitiator and the second stage cross-linking
agent is a thermal free radical initiator having a 10 hr t.sub.1/2
of about 65.degree. C. or greater if the first stage polymerization
initiator is a thermal free radical initiator having a 10 hr
t.sub.1/2 of about 55.degree. C. or less, wherein the first stage
of the method comprises polymerizing the ophthalmic device material
by activating the first stage polymerization initiator without
activating the second stage cross-linking agent; and the second
stage of the method comprises cross-linking the ophthalmic device
material by activating the second stage cross-linking agent.
2. The method of claim 1 wherein the aryl acrylic hydrophobic
monomers is selected from the group consisting of 2-phenoxyethyl
acrylate; 2-phenylethylthio acrylate; 2-phenylethylamino acrylate;
phenyl acrylate; benzyl acrylate; 2-phenylethyl acrylate;
3-phenylpropyl acrylate; 3-phenoxypropyl acrylate; 4-phenylbutyl
acrylate; 4-phenoxybutyl acrylate; 4-methylphenyl acrylate;
4-methylbenzyl acrylate; 2-2-methylphenylethyl acrylate;
2-3-methylphenylethyl acrylate; 2-4-methylphenylethyl acrylate; and
their corresponding methacrylate compounds.
3. The method of claim 1 wherein m is 2-4; Y is nothing or O; and
Ar is phenyl.
4. The method of claim 1 wherein the ophthalmic device material
comprises at least two aryl acrylic hydrophobic monomers of Formula
(I) and further wherein at least one of the aryl acrylic
hydrophobic monomers is a methacrylate monomer and at least one of
the aryl acrylic hydrophobic monomers is an acrylate monomer.
5. The method of claim 4 wherein the ophthalmic device materials
comprise a total of at least 50% (w/w) of aryl acrylic hydrophobic
monomers of Formula (I).
6. The method of claim 5 wherein the ophthalmic device materials
comprise a total of at least 70% (w/w) of aryl acrylic hydrophobic
monomers of Formula (I).
7. The method of claim 1 wherein the ophthalmic device material
further comprises one or more monomers selected from the group
consisting of C.sub.1-C.sub.8 alkylacrylates; C.sub.1-C.sub.8
cycloalkylacrylates; C.sub.1-C.sub.8 N-alkylacrylamides;
C.sub.1-C.sub.8 phenoxyalkylacrylates; and their corresponding
methacrylates.
8. The method of claim 1 wherein the first stage polymerization
initiator is selected from group consisting of thermal free radical
initiator having a 1 0 hr t.sub.1/2 of about 50.degree. C. or less;
UV-photoinitiators; and blue-light photoinitiators.
9. The method of claim 1 wherein the first stage polymerization
initiator is a blue-light photoinitiator.
10. The method of claim 1 wherein the amount of the first stage
polymerization initiator is about 3% (w/w) or less.
11. The method of claim 9 wherein the second stage cross-linking
agent is selected from the group consisting of dibenzoyl peroxide;
2, 4-dichlorodibenzoylperoxide; and dicumyl peroxide.
12. The method of claim 1 wherein the amount of the second stage
cross-linking agent is about 2-5% (w/w).
13. The method of claim 1 wherein the ophthalmic device material
further comprises one or more ingredients selected from the group
consisting of UV absorbing compounds and blue-light absorbing
compounds.
Description
[0001] This application is a continuation-in-part application of
co-pending U.S. patent application Ser. No. 09/283,592, filed Apr.
1, 1999, which claims priority from U.S. Provisional Patent
Application Serial No. 60/081,874, filed Apr. 15, 1998.
FIELD OF THE INVENTION
[0002] This invention relates to a method of preparing high
refractive index ophthalmic device materials. In particular, the
present invention relates to a two-stage method in which ophthalmic
device materials are first polymerized and then cross-linked.
BACKGROUND OF THE INVENTION
[0003] The two most common types of polymerization initiators for
ophthalmic device materials are thermal initiators and
photoinitiators. Typical thermal initiators, including free radical
initiators such as peroxides, initiate polymerization as
temperature is increased. In some cases, two or three temperature
tiers are involved such that curing involves a schedule of
temperature/time combinations. Thermal initiation generally
requires holding the monomer composition at elevated temperatures
for lengthy periods of time. Total cure times of twenty-four hours
are not unusual. See, for example, U.S. Pat. No. 5,290,892.
[0004] Photoinitiators generally offer the advantage of relatively
short cure times and, unlike thermal initiators, can be used at
ambient conditions, eliminating the need for high-temperature
equipment or special ovens. Photoinitiators are activated by
radiation of one or more specified wavelengths, rather than heat.
Photoinitiation of ophthalmic lens materials is known. See, for
example, U.S. Pat. No. 5,290,892.
[0005] The most common types of photoinitiators known or used for
curing ophthalmic lens polymers are probably UV-sensitive
photoinitiators. UV-sensitive photoinitiators are, however,
generally not suitable for use with lens materials that contain a
UV-absorbing chromophore. UV-absorbing chromophores present in an
ophthalmic lens composition can interfere with the ability of
UV-sensitive photoinitiators to efficiently cure the composition.
Today, UV-absorbing chromophores are frequently incorporated in
ophthalmic lens materials in order to reduce or block UV light from
reaching the retina. Although methods are known for temporarily
"blocking" UV absorbing chromophores during processing, thereby
preventing interference with a UV-initiator, these methods require
that the UV-absorber be "un-blocked" after the composition is
cured. The UV chromophore can be "un-blocked" by either chemical or
thermal means. "Un-blocking" is generally complicated and can add
4-6 hours to processing times, offsetting some or all of the time
advantages offered by photoinitiators.
[0006] In addition to UV-sensitive photoinitiators, visible-light
initiators are also known. For example, U.S. Pat. No. 5,224,957
discloses photopolymerizable compositions useful in forming an
intraocular lens in situ. The compositions are delivered into the
natural lens capsule or a thin plastic shell substitute and then
polymerized. The reference compositions contain 90-99.99% by weight
of at least one polyfunctional acrylic and/or methacrylic acid
ester. Suitable acid esters include bisphenol A or
bishydroxypolyalkoxy bisphenol A derivatives lengthened with
ethylene oxide or propylene oxide. The compositions of the '957
patent are cured using photoinitiators which absorb light in the
range 400-500 nm. Suitable initiators include alpha-diketones, in
particular camphorquinone, benzil and phenanthrene quinone, and
mono and bisacylphosphine oxides.
[0007] International Patent Application Publication No. WO 96/28762
also discloses photocurable compositions comprising acrylic
components. The compositions contain specified amounts of
di(meth)acrylates, poly(meth)acrylates, urethane(meth)acrylates,
and oligomeric di(meth)acrylates based on bisphenol A or bisphenol
F. The photoinitiator may be "any photoinitiator which forms free
radicals when irradiated suitably." Suitable classes include
benzoin ethers; acetophenones; benzil; anthraquinones;
benzoylphosphine oxides (e.g., 2, 4,
6-trimethylbenzoyidiphenylphosphine oxide); benzophenones.
Photoinitiators particularly suitable for use with argon ion lasers
include 2, 4, 6- trimethylbenzoyldiphenylphosphine oxide.
[0008] Some ophthalmic devices are obtained by a monomer cast
polymerization method. In such a method, the monomer solution is
cast directly into a mold of desired shape and then polymerized or
cured, followed by any machining or polishing, etc. See, for
example, U.S. Pat. Nos. 4,921,205 and 5,290,892.
[0009] In other cases, ophthalmic device materials are formed by
first preparing a "prepolymer" or partially cured material,
followed by further curing. See, for example, U.S. Pat. No.
5,374,663 describing a prepolymer process for producing a U.V.
absorber-containing intraocular lens material in which a monomer
solution comprising a lens-forming monomer, an U.V. absorber and a
polymerization initiator is introduced into a reactor and heated
for a length of time and at a temperature sufficient to obtain a
prepolymer of high viscosity. Thereafter, the prepolymer is
filtered, cast into a cell or mold and further heated for a time at
a temperature sufficient to obtain a transparent lens material.
[0010] According to the '663 patent, the prepolymer process has the
advantage that the prepolymer scarcely leaks out of the cell or
mold because of its high viscosity, and that the degree of
shrinkage in the step of obtaining a lens material from the
prepolymer is small. On the other hand, the prepolymer process has
some problems as well, including (i) the control of the
polymerization degree and viscosity of the prepolymer obtained in
the first polymerization step, and (ii) when a cross-linking
monomer is contained in the material, an insoluble polymer is
formed in the prepolymer step, making any filtration treatment
difficult or impossible, and the polymer produced after the further
curing step becomes "non-uniform."
SUMMARY OF THE INVENTION
[0011] The present invention relates to a method for preparing
acrylic, high refractive index ophthalmic device materials. The
ophthalmic device materials comprise at least one aryl acrylic
hydrophobic monomer, a first stage polymerization initiator
selected from the group consisting of photoinitiators and thermal
free radical initiators having a ten hour half-life ("10 hr
t.sub.1/2") of about 50.degree. C. or less, and a second stage
cross-linking agent. If the first stage initiator is a
photoinitiator, the second stage cross-linking agent is a thermal
free radical initiator having a 10 hr t.sub.1/2 of about 50.degree.
C. or greater. If the first stage initiator is a thermal free
radical initiator having a 10 hr t.sub.1/2of about 50.degree. C. or
less, the second stage cross-linking agent is a thermal free
radical initiator having a 10 hr t.sub.1/2 of about 65.degree. C.
or greater. The monomers used to form the ophthalmic device
materials do not contain any ingredient having more than one
unsaturated site, as such ingredients will cause premature
cross-linking.
[0012] According to the present invention, the ophthalmic device
material is prepared using a two-stage process. In the first stage,
the material is polymerized such that the second stage
cross-linking agent is not activated. In the second stage, the
material is cross-linked by activating the second stage
cross-linking agent. The two-stage process of the present invention
can provide enhanced control of material shrinkage and stress
problems associated with cast molding operations compared to single
stage curing processes.
DETAILED DESCRIPTION OF THE INVENTION
[0013] As used herein, "high refractive index" means a refractive
index of about 1.50 or greater when measured at room temperature
using an Abbe' refractometer at 589 nm (Na light source).
[0014] According to the present invention, acrylic, high refractive
index ophthalmic device materials are prepared in two stages. In
the first stage, the device material is polymerized. In the second
stage, the device material is cross-linked.
[0015] The ophthalmic device materials of the present invention
comprise at least one compound of Formula I below. 1
[0016] wherein: X is H or CH.sub.3;
[0017] m i0-10;
[0018] Y is nothing, O, S, or NR wherein R is H, CH.sub.3,
C.sub.nH.sub.2n+1(n=1-10) iso OC.sub.3H.sub.7, C.sub.6H.sub.5, or
CH.sub.2C.sub.6H.sub.5;
[0019] Ar is any aromatic ring which can be unsubstituted or
substituted with CH.sub.3, C.sub.2H.sub.5, n-C.sub.3H.sub.7,
iso-C.sub.3H.sub.7, OCH.sub.3, C.sub.6H.sub.11, Cl, Br,
C.sub.6H.sub.5, or CH.sub.2C.sub.6H.sub.5.
[0020] Monomers of Formula I are known and include, but are not
limited to: 2-phenoxyethyl acrylate; 2-phenylethylthio acrylate;
2-phenylethylamino acrylate; phenyl acrylate; benzyl acrylate;
2-phenylethyl acrylate; 3-phenylpropyl acrylate; 3-phenoxypropyl
acrylate; 4-phenylbutyl acrylate; 4-phenoxybutyl acrylate;
4-methylphenyl acrylate; 4-methylbenzyl acrylate;
2-2-methylphenylethyl acrylate; 2-3-methylphenylethyl acrylate;
2-4-methylphenylethyl acrylate; and their corresponding
methacrylate compounds. These acrylic/methacrylic monomers and
others are disclosed in U.S. Pat. No. 5,290,892, the entire
contents of which are hereby incorporated by reference.
[0021] Preferred monomers of Formula (I) are those where m is 2-4;
Y is nothing or 0; and Ar is phenyl. Most preferred are
2-phenylethyl acrylate, 2-phenoxyethyl acrylate, 3-phenylpropyl
acrylate, 3-phenoxypropyl acrylate, 4-phenylbutyl acrylate, and
4-phenoxybutyl acrylate, and their corresponding methacrylate
compounds.
[0022] The ophthalmic device materials of the present invention
preferably contain at least two monomers of Formula I, wherein at
least one is a methacrylate monomer (X=CH.sub.3) and at least one
is an acrylate monomer (X=H). The exact amount of monomer of
Formula I present in the acrylic, high refractive index ophthalmic
device materials of the present invention will vary depending upon
the identity of the monomer(s) of Formula I, the identity of any
other device-forming monomer(s) present in the materials, and the
desired mechanical properties. For example, foldable intraocular
lenses are preferably made from polymers having a glass transition
temperature no greater than normal room temperature, e.g., about
20-25.degree. C., in order that the lenses can be rolled or folded
conveniently at room temperature. Materials having a glass
transition temperature of about 15.degree. C. or less are even more
preferred for foldable intraocular lens applications. Glass
transition temperature is determined at room temperature using a
differential scanning calorimeter at a heating rate of 10.degree.
C./min.
[0023] Additionally, materials exhibiting an elongation of at least
150% when measured at room temperature using an Instron tensile
tester at a cross-head speed of 50 cm/min are preferred for use in
foldable intraocular lenses because such lenses must exhibit
sufficient strength to allow them to be folded without fracturing.
For foldable intraocular lens applications, polymers having an
elongation of at least 200% are more preferred.
[0024] In general, the acrylic, high refractive index ophthalmic
device materials of the present invention preferably contain at
least 50% (w/w) of monomer(s) of Formula I. In a more preferred
embodiment, the device materials will contain one or more monomers
of Formula I in an amount totaling 70% (w/w) or more, and most
preferably, 80% (w/w) or more.
[0025] Device-forming monomers other than those of Formula I
optionally may be included in the materials of the present
invention. Many such ophthalmic device-forming monomers are known.
Any known device-forming monomer may be used if it is compatible
with the monomer(s) of Formula I present in the ophthalmic device
material and does not prevent the ability of the stage 1
polymerization initiator to cure the material such that the
material contains no cross-linking or is substantially free of
cross-linking. Suitable device-forming monomers other than those of
Formula I include, but are not limited to: C.sub.1-C.sub.8
alkylacrylates, C.sub.1-C.sub.8 cycloalkylacrylates,
N-alkylacrylamides (where alkyl=C.sub.1-C.sub.4),
phenoxyalkylacrylates (where alkyl=C.sub.1-C.sub.8), and their
corresponding methacrylates. Suitable device-forming monomers other
than those of Formula I also include N-vinylpyrrolidone. See U.S.
Pat. No. 5,331,073, the entire contents of which are hereby
incorporated by reference, for examples of device-forming materials
other than those of Formula 1.
[0026] As in the case of the monomer(s) of Formula I, the amount of
any other device-forming monomers present in the ophthalmic device
materials of the invention will vary depending upon the identity of
the monomer(s) of Formula I, the identity of the optional
device-forming monomer(s), and the mechanical properties desired
for the finished ophthalmic material. In general, for foldable
intraocular lens applications, the ophthalmic device materials of
the present invention preferably contain about 45% (w/w) or less,
and more preferably about 30% (w/w) or less, of device-forming
monomers other than those of Formula I.
[0027] The ophthalmic device materials also comprise a first stage
polymerization initiator selected from the group consisting of
photoinitiators and thermal free radical initiators having a 10 hr
t.sub.1/2 of about 55.degree. C. or less, preferably about
50.degree. C. or less. Suitable photoinitiators include, but are
not limited to, UV- and blue-light photoinitiators. Many such
photoinitiators are known. Preferred blue-light photoinitiators are
benzoylphosphine oxide initiators, such as 2, 4,
6-trimethyl-benzoyldiphenylophosphine oxide; bis-(2,
6-dichlorobenzoyl)-4-N-propylphenyl-phosphine oxide; and bis-(2,
6-dichlorobenzoyl)-4-N-butylphenylphosphine oxide. Most preferred
is 2, 4, 6-trimethyl-benzoyidiphenylophosphine oxide, commercially
available as Lucirin.RTM. TPO from BASF Corporation (Charlotte,
North Carolina). See, for example, U.S. Pat. No. 5,891,931, the
entire contents of which are hereby incorporated by reference.
[0028] Many thermal free radical initiators having a 10 hr
t.sub.1/2of about 55.degree. C. or less are known, including but
not limited to, both peroxide- and azo-type compounds. Suitable
peroxide- and azo-type compounds include, for example, those having
a 10 hr t.sub.1/2 of about 55.degree. C. or less that are listed in
Tables 1 and 2 below.
[0029] The amount of the first stage polymerization initiator in
the device materials of the present invention will depend upon the
identity of the other ingredients in the materials, the curing
conditions, etc. In general, however, the amount of first stage
polymerization initiator contained in the mixture to be polymerized
in stage 1 of the present invention will be about 3% (w/w) or less,
preferably about 2 % (w/w) or less, and most preferably about 1%
(w/w).
[0030] In addition to the device-forming monomer(s) (i.e., monomers
of Formula I and any other device forming monomers) and the first
stage polymerization initiator, the ophthalmic device materials of
the present invention contain a second stage cross-linking agent.
If the first stage initiator is a photoinitiator, the second stage
cross-linking agent is a thermal free radical initiator having a 10
hr t.sub.1/2 of about 50.degree. C. or greater. If the first stage
initiator is a thermal free radical initiator having a 10 hr
t.sub.1/2 of about 55.degree. C. or less, the second stage
cross-linking agent is a thermal free radical initiator having a 10
hr t.sub.1/2 of about 65.degree. C. or greater, preferably about
70.degree. C. or greater. Many free radical initiators having a 10
hr t.sub.1/2 of about 50.degree. C. or greater are known, including
but not limited to the peroxide- and azo-type compounds that are
listed in Tables 1 and 2 below. Dicumyl peroxide is the preferred
second stage cross-linking agent for use with ophthalmic device
materials comprising 2-phenylethyl acrylate and 2-phenylethyl
methacrylate.
[0031] The amount of the second stage cross-linking agent contained
in the device materials of the present invention will depend upon,
among other factors, the degree of cross-linking desired. In
general, however, the amount of second stage cross-linking agent in
the ophthalmic device materials will be about 2-5% (w/w), and
preferably about 2.5-4% (w/w).
[0032] In order to prevent premature cross-linking, the ophthalmic
device materials of the present invention do not contain any
ingredient having more than one unsaturated bond. Such ingredients
include the common cross-linking monomers ethyleneglycol
dimethacrylate; diethylene glycol dimethacrylate; ethyleneglycol
diacrylate; allyl methacrylates; allyl acrylates; 1, 3-propanediol
dimethacrylate; 1, 6-hexanediol dimethacrylate; 1, 4-butanediol
dimethacrylate; polyethyleneoxide mono- and diacrylates; and the
like.
[0033] Ultraviolet absorbing chromophores are optionally included
in the ophthalmic device materials of the present invention. Such
chromophores prevent or inhibit UV light from damaging the eye. The
ultraviolet absorbing chromophore in the device material of the
present invention 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, and which is compatible with
the device-forming monomer(s) present in the material . The
ultraviolet absorbing compound is incorporated into the monomer
mixture and is entrapped in the polymer matrix when the monomer
mixture is polymerized. Suitable ultraviolet absorbing compounds
include substituted benzophenones, such as 2-hydroxybenzophenone,
and 2-(2-hydroxyphenyl)-benzotriazoles. It is preferred to use an
ultraviolet absorbing compound that is copolymerizable with the
device-forming monomers described above so that it will be
covalently bound to the polymer matrix. In this way, possible
leaching of the ultraviolet absorbing compound out of the device
and into the interior of the eye is minimized. Suitable
copolymerizable ultraviolet absorbing compounds are the substituted
2-hydroxybenzophenones disclosed in U.S. Pat. No. 4,304,895 and the
2-hydroxy-5-acryloxyphenyl-2H-benzotriazoles disclosed in U.S. Pat.
No. 4,528,311. The most preferred ultraviolet absorbing compound is
2-(3'-methallyl-2'-hydroxy-5'-methyl phenyl) benzotriazole.
[0034] If the ophthalmic device material does include a
UV-absorber, it is unlikely that a UV polymerization initiator may
be used as the first stage polymerization initiator. In such cases,
the first stage polymerization initiator will likely have to be
thermal initiator having a 10 hr t.sub.1/2 of about 55.degree. C.
or less or a blue-light initiator in order to avoid interference
with the UV-absorber.
[0035] Blue-light absorbing compounds are also optionally included
in the device materials of the present invention. If a blue-light
absorbing compound, e.g. a yellow dye, is included in the device
material of the present invention, then the first stage
polymerization initiator will likely not be a blue-light
photoinitiator. In the event the device material contains both a
UV-absorber and a blue-light absorbing compound, the first stage
polymerization initiator will likely be a low temperature thermal
initiatior. Preferably, blue-light absorbers are copolymerizable
with the device-forming monomers. Suitable polymerizable blue-light
blocking chromophores include those disclosed in U.S. Pat. No.
5,470,932.
[0036] The device materials of this invention are prepared by
forming a mixture comprising the device-forming monomer(s)
(monomer(s) of Formula I and any optional device-forming
monomer(s)), the first stage polymerization initiator and the
second stage cross-linking agent, along with any UV- or blue-light
absorbing compounds and any other suitable ingredients, in the
desired proportions. The mixture can then be introduced into a mold
of desired shape to form an ophthalmic device. Alternatively, the
mixture can be cast in sheets from which the finished form can be
obtained by compression molding (generally with mild
pre-heating).
[0037] In either case (direct cast molding in final form or casting
in sheets for subsequent molding), the ophthalmic device material
is polymerized in the first stage of the present invention by
activating the first stage polymerization initiator (e.g., using
heat, UV- or blue-light). In the case where the first stage
polymerization initiator is a low temperature thermal initiator and
the second stage cross-linking agent is dicumyl peroxide, the
thermal initiator may be activated by exposure to temperatures of
up to approximately 55.degree. C. or so without activating the
dicumyl peroxide. The curing parameters, e.g., length of exposure
and temperature or intensity of light source, are preferably chosen
to accomplish complete polymerization.
[0038] After the ophthalmic device material is polymerized in stage
1, it is cross-linked in stage 2 of the present invention.
Cross-linking is achieved by activating the second stage
cross-linking agent using heat. The temperature and length of
exposure to heat are determined by the identity and amount of the
second stage cross-linking agent and the desired degree of
cross-linking to be achieved (i.e., the desired physical properties
of the ophthalmic device materials). In the case where the second
stage cross-linking agent is dicumyl peroxide, the activation
temperature will be about 115.degree. C. or greater. The duration
of heating to achieve the second-stage cross-linking is preferably
about four times the half-life of the second stage cross-linking
agent at the chosen activation temperature. In the case of dicumyl
peroxide and an activation temperature of approximately 135.degree.
C., the duration of heating is approximately 4 hours.
[0039] The ophthalmic device materials prepared according to the
present invention may be used to make almost any type of ophthalmic
lens, including contact lenses, intracorneal lenses and intraocular
lenses. Ophthalmic lenses constructed of the disclosed materials
can be of any design, but are preferably intraocular lenses (lOLs)
capable of being rolled or folded and inserted through a relatively
small incision. For example, the lOLs can be of what is known as a
one piece or multipiece design. Typically, an IOL comprises an
optic and at least one haptic. The optic is that portion which
serves as the lens and the haptics are attached to the optic and
are like arms that hold the optic in its proper place in the eye.
The optic and haptic(s) can be of the same or different material.
Haptics may be attached to the optic using conventional techniques.
In a single piece lens, the optic and the haptics are formed out of
one piece of material. Depending on the material, the haptics are
then cut, or lathed, out of the material to produce the IOL. In
addition to ophthalmic lenses, the materials prepared according to
the methods of the present invention may also be used to make other
ophthalmic devices including, but not limited to, keratoprostheses
and corneal inlays or rings.
[0040] Molding and drilling operations are easily carried out if
the device, e.g., an IOL optic, is molded between two polypropylene
mold halves. The mold containing the cured device material is then
placed on a lathe and cut to the desired shape. The mold may then
be easily mounted to carry out any drilling operations prior to
removing the mold halves. Both the lathing and drilling operations
may be facilitated by cooling the mold/device in a freezer to less
than 10.degree. C. and preferably less than 0.degree. C. prior to
each of these operations. If premature release of one or both mold
halves occurs, it may be necessary to use clamps or alternative
mold materials or to pretreat the surface of the mold halves.
1TABLE 1 Peroxide initiators (Solvent = 0.2M benzene) 10 hr
t.sub.1/2 Name (.degree. C.) Diacyl peroxides dibenzoyl peroxide
(BPO) 73 di(2,4-dichlorobenzoyl) peroxide 54 diacetyl peroxide 69
dilauroyl peroxide 62 Peroxyesters t-butyl perbenzoate 105 t-butyl
peracetate 102 2,5-di(benzoylperoxy)-2,5-di- methylhexane 100
di-t-butyl diperoxyazelate 99 t-butyl peroxy-2-ethyl-hexanoate 73
t-amyl peroctoate 70 t-butyl peroxyneodecanoate 47
Peroxydicarbonates di(n-propyl)peroxydicarbonate (Lupersol 50 221)
di(4-t-butylcyclohexyl)peroxydicarbonate 43 Diperoxyketals ethyl
3,3-di(t-butylperoxy)butyrate 111 2,2-di(t-butylperoxy)-b- utane
104 2,2-di(t-butylperoxy)-4-methylpentane 101
1,1-di(t-butylperoxy)-cyclohexane 95 1,1-di(t-butylperoxy)-3,3,5--
trimethyl- cyclohexane Dialkyl peroxides dicumyl peroxide 115
di-t-butyl peroxide 126 2,6-di(t-butylperoxy)-2,5-dimethylhexane
119
[0041]
2TABLE 2 Azo initiators Wako Product 10 hr t.sub.1/2 Name No.*
(.degree. C.) solvent 10 hr t.sub.1/2 .ltoreq. 65.degree. C.
2,2'-azobisisobutyronitrile (AIBN) V-60 65 toluene
2,2'-azobis(2,4-dimethyl-valeronitrile) V-65 51 toluene
2,2'-azobis(4-methoxy-2,4-dimethyl- V-70 30 toluene valeronitrile)
2,2'-azobis(N,N'-dimethylene- VA-044 44 water
isobutyramidine)dihydrochloride 2,2'-azobis(2-amidino-propane)dihy-
dro- V-50 56 water chloride 2,2'-azobis(N,N'-dimethylene- VA-061 61
methanol isobutyramidine) 10 hr t.sub.1/2 > 65.degree. C.
dimethyl-2,2'-azobisisobutyate V-601 66 toluene
2,2'-azobis(2-methylbutyronitrile) V-59 67 toluene
1,1'-azobis(1-cyclohexanecarbonitrile) V-40 88 toluene
2-(carbamoylazo)-isobutyronitrile V-30 104 toluene
2,2'-azobis(2,4,4-trimethyl-pentane) VR-110 110 diphenyl- ether
2-phenylazo-2,4-dimethyl-4-methoxy- V-19 122 xylene valeronitrile
2,2'-azobis(2-methylpropane) VR-160 160 gas phase
4,4'-azobis(4-cyanopentanoic acid) V-501 69 water
2,2'-azobis{2-methyl-N-[1,1- VA-080 80 water
bis(hydroxymethyl)-2-hydroxy- ethyl]propionamide}
2,2'-azobis{2-methyl-N-[1,1- VA-082 82 water
bis(hydroxymethyl)ethyl]propionamide} 2,2'-azobis[2-methyl-N-(2-
VA-086 86 water hydroxyethyl)propionamide]
2,2'-azobis(isobutyramide)dihydrate VA-088 88 water *Wako Chemicals
USA, Inc. (Richmond, Virginia)
[0042] The invention will be further illustrated by the following
examples which are intended to be illustrative, but not
limiting.
EXAMPLES
[0043] The ophthalmic device materials shown below in Table 3 were
prepared as follows:
[0044] Example 1 was prepared by heating at 70.degree. C. for 7
hours, followed by heating at 100.degree. C. for 7 hours.
[0045] Example 2 was prepared by heating at 135.degree. C. for 17.5
hours.
[0046] Examples 3-14 were prepared using the two-stage method of
the present invention. In stage 1, the ingredients were mixed,
transferred to 1-mm thick, slab, polypropylene mold, and
polymerized by exposure to blue light (Palatray CU/14 mW/cm .sup.2)
for 15 minutes. In stage 2, the materials remained in the same slab
molds and were cross-linked by heating at 135.degree. C. for 4, 6
or 10 hours as indicated. In all cases (Examples 1-14) the
ophthalmic device materials were vacuum degassed for approximately
10 minutes immediately prior to filling and sealing the
polypropylene slab molds.
[0047] The amount of each of the ingredients is expressed in %
w/w.
3 TABLE 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 PEA 65 65 65 65 65 60 60
60 55 55 55 50 50 50 PEMA 30 30 30 30 30 35 35 35 40 40 40 45 45 45
OMTP 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8
Lucirin TPO -- 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
DiCuP -- 4 4 4 4 4 4 4 4 4 4 4 4 4 BDDA 3.2 -- -- -- -- -- -- -- --
-- -- -- -- -- Perkadox-16 1.8 -- -- -- -- -- -- -- -- -- -- -- --
-- Cure -- 17.5 4 6 10 4 6 10 4 6 10 4 6 10 hrs @ 135 C. Tg
(.degree. C.) -- 14.7 0.0 4.3 0.2 5.5 3.8 3.6 6.9 3.5 5.9 6.3 7.9
9.1 % Acetone uptake -- 53.9 60.2 58.3 54.6 59.1 55.9 55.5 61.3
59.0 56.8 62.3 59.7 57.9 % Acetone -- 4.56 4.98 4.96 3.75 4.69 5.04
4.56 6.15 4.66 4.38 6.44 5.50 5.15 extractables Stress (psi) 1200
-- 1120 1176 959 1250 1183 1115 1203 1252 1278 1148 1332 1279 %
Strain 600 -- 1440 1236 965 1215 1156 952 1096 963 872 648 676 654
Modulus, secant 300 -- 227 218 203 391 340 352 572 676 554 1038
1073 1040 (psi) Modulus, Young -- -- 452 410 327 810 760 645 1164
1247 1049 1828 1892 1837 (psi) PEA = 2-phenylethylacrylate PEMA =
2-phenylethylmethacrylate oMTP = o-Methallyl Tinuvin P
(2-(3'-methallyl-2'-hydroxy-5'-methyl phenyl)-benzotriazole)
Lucirin TPO = 2,4,6-trimethyl-benzoyldiphe- nylophosphine oxide
BDDA = 1,4-butanediol diacrylate DiCuP = dicumyl peroxide Perkadox
16 = di-(4-tert-butylcyclohexyl)perox- ydicarbonate
[0048] The invention has been described by reference to certain
preferred embodiments; however, it should be understood that it may
be embodied 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 restrictive, the scope of the
invention being indicated by the appended claims rather than by the
foregoing description.
* * * * *