U.S. patent application number 12/060322 was filed with the patent office on 2008-07-31 for high refractive-index, hydrophilic monomers and polymers, and ophthalmic devices comprising such polymers.
Invention is credited to Jay F. Kunzler, Richard M. Ozark, Joseph C. Salamone.
Application Number | 20080183006 12/060322 |
Document ID | / |
Family ID | 37331447 |
Filed Date | 2008-07-31 |
United States Patent
Application |
20080183006 |
Kind Code |
A1 |
Salamone; Joseph C. ; et
al. |
July 31, 2008 |
High Refractive-Index, Hydrophilic Monomers and Polymers, and
Ophthalmic Devices Comprising Such Polymers
Abstract
A hydrophilic, aromatic-based monomer has an aromatic group
substituted with at least one hydrophilic substituent and a
reactive functional group. Polymers comprising such a hydrophilic,
aromatic-based monomers avoid or reduce the risk of forming
vacuoles of absorbed water. Furthermore, such polymers have high
refractive index, and, thus, are advantageously used for making
ophthalmic devices, such as intraocular lenses, contact lenses,
corneal rings, corneal inlays, and keratoprostheses.
Inventors: |
Salamone; Joseph C.;
(Fairport, NY) ; Kunzler; Jay F.; (Canandaigua,
NY) ; Ozark; Richard M.; (Solvay, NY) |
Correspondence
Address: |
Toan P. Vo;Bausch & Lomb Incorporated
One Bausch & Lomb Place
Rochester
NY
14604
US
|
Family ID: |
37331447 |
Appl. No.: |
12/060322 |
Filed: |
April 1, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11139276 |
May 27, 2005 |
|
|
|
12060322 |
|
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Current U.S.
Class: |
560/221 |
Current CPC
Class: |
C08F 220/30 20130101;
C08L 33/14 20130101; G02B 1/043 20130101; C08F 220/18 20130101;
G02B 1/043 20130101; C08F 220/54 20130101 |
Class at
Publication: |
560/221 |
International
Class: |
C07C 69/52 20060101
C07C069/52 |
Claims
1. A compound having a formula of G-D-Ar (I) wherein Ar is a
C.sub.6-C.sub.24 aromatic group having a hydrophilic substituent
selected from the group consisting of --COOH,
--CH.sub.2--CH.sub.2OH, --(CHOH).sub.2--CH.sub.2OH,
--CH.sub.2--CHOH--CH.sub.2OH, --C(O)O--NH.sub.2,
--C(O)--N(CH.sub.3).sub.2, poly(alkyleneglycol) and combinations
thereof, D is a divalent linking group, and G is a reactive
functional group.
2. The compound of claim 1, wherein the hydrophilic substituent is
selected from the group consisting of --COOH,
--CH.sub.2--CH.sub.2OH, and combinations thereof.
3. The compound of claim 1, wherein the hydrophilic substituent is
poly(alkylene glycol).
4. The compound of claim 6, wherein said poly(alkylene glycol) is
poly(ethylene glycol) having a formula of
--(O--CH.sub.2--CH.sub.2).sub.nOH, wherein n is an integer and
1.ltoreq.n.ltoreq.50.
5. A compound having a formula of G-D-Ar (I) wherein Ar is a
C.sub.6-C.sub.24 aromatic group having a hydrophilic substituent
selected from the group consisting of carboxamide,
dialkyl-substituted carboxamide, amino, alkanolamino, sulfonate,
phosphonate, sulfate, phosphate, ureido, substituted sugars, and
combinations thereof, D is a divalent linking group, and G is a
reactive functional group.
6. The compound of claim 1, wherein G is selected from the group
consisting of vinyl, allyl, acryloyl, acryloyloxy, methacryloyl,
methacryloyloxy, epoxide, isocyanate, isothiocyanate, amino,
hydroxyl, mercapto, anhydride, carboxylic, fumaryl, styryl, and
combinations thereof.
7. The compound of claim 1, wherein D is selected from the group
consisting of saturated straight C.sub.1-C.sub.10 hydrocarbons,
unsaturated straight C.sub.1-C.sub.10 hydrocarbons, saturated
branched C.sub.3-C.sub.10 hydrocarbons, unsaturated branched
C.sub.3-C.sub.10 hydrocarbons, saturated cyclic C.sub.3-C.sub.10
hydrocarbons, unsaturated cyclic C.sub.3-C.sub.10 hydrocarbons, and
alkyloxy substituents.
8. The compound of claim 1, wherein the compound has a formula of
##STR00009## wherein R is hydrogen or CH.sub.3; D is a divalent
group selected from the group consisting of saturated straight
C.sub.1-C.sub.10 hydrocarbons, unsaturated straight
C.sub.1-C.sub.10 hydrocarbons, saturated branched C.sub.3-C.sub.10
hydrocarbons, unsaturated branched C.sub.3-C.sub.10 hydrocarbons,
saturated cyclic C.sub.3-C.sub.10 hydrocarbons, unsaturated cyclic
C.sub.3-C.sub.10 hydrocarbons, and alkoxy substituents; E is
selected from the group consisting of carboxy, carboxamide, and
monohydric and polyhydric alcohol substituents; and m is an integer
from 1 to, and including, 5.
9. The compound of claim 1, wherein the compound is ##STR00010##
wherein R is hydrogen or CH.sub.3.
10. The compound of claim 1, wherein the compound is ##STR00011##
wherein R is hydrogen or CH.sub.3.
11. The compound of claim 1, wherein the hydrophilic,
aromatic-based monomer has a formula of ##STR00012## wherein R is
hydrogen or CH.sub.3, and R.sup.1 is --C(O)O--NH.sub.2 or
--C(O)--N(CH.sub.3).sub.2.
Description
CROSS REFERENCE
[0001] This application is a divisional of patent application Ser.
No. 11/139,276 filed May 27, 2005 which is incorporated by
reference herein
BACKGROUND OF THE INVENTION
[0002] The present invention relates to high refractive-index,
hydrophilic monomers and polymers, and ophthalmic devices
comprising such polymers. In particular, the present invention
relates to high refractive-index, aromatic-based, hydrophilic
monomers and polymers, and ophthalmic devices comprising such
polymers.
[0003] Since the 1940s ophthalmic devices in the form of
intraocular lens ("IOL") implants have been utilized as
replacements for diseased or damaged natural ocular lenses. In most
cases, an intraocular lens is implanted within an eye at the time
of surgically removing the diseased or damaged natural lens, such
as for example, in the case of cataracts. For decades, the
preferred material for fabricating such intraocular lens implants
was poly(methyl methacrylate), which is a rigid, glassy
polymer.
[0004] Softer, more flexible IOL implants have gained in popularity
in more recent years due to their ability to be compressed, folded,
rolled or otherwise deformed. Such softer IOL implants may be
deformed prior to insertion thereof through an incision in the
cornea of an eye. Following insertion of the IOL in an eye, the IOL
returns to its original pre-deformed shape due to the memory
characteristics of the soft material. Softer, more flexible IOL
implants as just described may be implanted into an eye through an
incision that is much smaller, i.e., less than 4.0 mm, than that
necessary for more rigid IOLs, i.e., 5.5 to 7.0 mm. A larger
incision is necessary for more rigid IOL implants because the lens
must be inserted through an incision in the cornea slightly larger
than the diameter of the inflexible IOL optic portion. Accordingly,
more rigid IOL implants have become less popular in the market
since larger incisions have been found to be associated with an
increased incidence of postoperative complications, such as induced
astigmatism.
[0005] With recent advances in small-incision cataract surgery,
increased emphasis has been placed on developing soft, foldable
materials suitable for use in artificial IOL implants. In general,
the materials of current commercial IOLs fall into one of three
general categories: silicones, hydrophilic acrylics and hydrophobic
acrylics.
[0006] In general, high water content hydrophilic acrylics, or
"hydrogels," have relatively low refractive indices, making them
less desirable than other materials with respect to minimal
incision size. Low refractive-index materials require a thicker IOL
optic portion to achieve a given refractive power. Silicone
materials may have a higher refractive index than high-water
content hydrogels, but tend to unfold explosively after being
placed in the eye in a folded position. Explosive unfolding can
potentially damage the corneal endothelium and/or rupture the
natural lens capsule and associated zonules. Low
glass-transition-temperature hydrophobic acrylic materials are
desirable because they typically have a high refractive index and
unfold more slowly and more controllably than silicone materials.
Unfortunately, low glass-transition-temperature hydrophobic acrylic
materials, which contain little or no water initially, tend to
absorb water over time and form pockets of water or vacuoles in
vivo, causing light reflections or "glistenings." Furthermore, it
may be difficult to achieve ideal folding and unfolding
characteristics due to the temperature sensitivity of some acrylic
polymers.
[0007] Because of the noted shortcomings of current polymeric
materials available for use in the manufacture of ophthalmic
implants, there is a need for stable, biocompatible polymeric
materials having desirable physical characteristics and refractive
indices.
SUMMARY OF THE INVENTION
[0008] In general, the present invention provides hydrophilic
monomers having high refractive indices and polymeric compositions
comprising such monomers.
[0009] In one aspect, the present invention provides hydrophilic,
aromatic-based monomers and polymeric compositions comprising such
monomers.
[0010] In another aspect, a hydrophilic, aromatic-based monomer of
the present invention has a formula of
G-D-Ar (I)
wherein Ar is a C.sub.6-C.sub.24 aromatic group having at least a
hydrophilic substituent, D is a divalent linking group, and G is a
reactive functional group.
[0011] In still another aspect, a polymeric composition comprises a
copolymer of at least two hydrophilic, aromatic-based monomers of
the present invention or a copolymer of an aromatic-based monomer
of the present invention and at least one other monomer.
[0012] In still another aspect, said at least one other monomer is
selected from hydrophilic monomers, hydrophobic monomers, and
combinations thereof.
[0013] In yet another aspect, the present invention provides a
method of making a high refractive index hydrophilic monomer. The
method comprises providing a C.sub.6-C.sub.24 aromatic compound
having at least one hydrophilic substituent and at least a reactive
functional group; and converting said at least a reactive
functional group to a polymerizable functional group.
[0014] In yet another aspect, the present invention provides a
method of making a hydrophilic polymeric composition having a high
refractive index. The method comprises polymerizing a hydrophilic,
aromatic-based monomer or polymerizing such a monomer and at least
a different monomer.
[0015] In yet another aspect, an ophthalmic device comprises a
polymeric material that comprises residues of at least a
hydrophilic, aromatic-based monomer of the present invention.
[0016] Other features and advantages of the present invention will
become apparent from the following detailed description and
claims.
DETAILED DESCRIPTION OF THE INVENTION
[0017] In general, the present invention provides hydrophilic
monomers having high refractive indices and polymeric compositions
comprising such monomers. The polymeric compositions of the present
invention have refractive index of about 1.4 or greater. In some
embodiments, the refractive index is in the range from about 1.4 to
about 1.7. In some other embodiments, the refractive index is in
the range from about 1.45 to about 1.6.
[0018] In one aspect, a polymeric composition of the present
invention has an equilibrium water content of greater than about
4.5 percent (by weight), thus avoiding problems related to the
formation of water vacuoles. In addition, a polymeric composition
of the present invention can have a relatively high elongation,
such as about 80 percent or greater. Accordingly, in many aspects,
the subject polymeric compositions are more suitable for use in the
manufacture of ophthalmic devices than many prior-art polymeric
materials.
[0019] Current commercial acrylic-based ophthalmic products have a
water content less than 4.5 percent by weight. These hydrophobic
products tend to absorb water over time in vivo and form water
vacuoles or "glistenings." In contrast, a polymeric composition
comprising residues of hydrophilic monomers of the present
invention tend to absorb water rapidly to equilibrium level.
Although, applicants do not wish to be bound to any particular
theory, it is believed that the absorbed water also is distributed
throughout the polymeric composition because of its association
with the hydrophilic substituents in the aromatic groups.
Therefore, polymeric compositions of the present invention do not
present the risk of formation of water vacuoles in vivo.
[0020] A hydrophilic aromatic-based monomer of the present
invention has a formula of
G-D-Ar (I)
wherein Ar is a C.sub.6-C.sub.24 aromatic group having at least a
hydrophilic substituent, D is a divalent linking group, and G is a
reactive functional group. The term "C.sub.6-C.sub.24 aromatic
group" means the aromatic group having 6-24 carbon atoms, excluding
any carbon atoms in the substituent group.
[0021] In one embodiment, Ar is a phenyl group having at least a
hydrophilic substituent.
[0022] In another embodiment, at least a hydrophilic substituent on
the aromatic group is selected from the group consisting of
carboxy, alcohols (including monohydric and polyhydric alcohols),
and combinations thereof.
[0023] In another embodiment, at least a hydrophilic substituent on
the aromatic group is selected from the group consisting of --COOH,
--CH.sub.2--CH.sub.2OH, --(CHOH).sub.2--CH.sub.2OH,
--CH.sub.2--CHOH--CH.sub.2OH, and combinations thereof.
[0024] In still another embodiment, at least a hydrophilic
substituent on the aromatic group is a poly(alkylene glycol), such
as poly(ethylene glycol) having a formula of
--(O--CH.sub.2--CH.sub.2).sub.nOH, wherein n is an integer and
1.ltoreq.n.ltoreq.100, preferably 1.ltoreq.n.ltoreq.50, and more
preferably, 1.ltoreq.n.ltoreq.20.
[0025] In a further embodiment, said hydrophilic substituent is
selected from the group consisting of carboxamide,
dialkyl-substituted carboxamide, amino, alkanolamino, sulfonate,
phosphonate, sulfate, phosphate, ureido, substituted sugars, and
combinations thereof.
[0026] In another aspect, G is a reactive functional group selected
from the group consisting of vinyl, allyl, acryloyl, acryloyloxy,
methacryloyl, methacryloyloxy, epoxide, isocyanate, isothiocyanate,
amino, hydroxyl, mercapto, anhydride, carboxylic, fumaryl, styryl,
and combinations thereof.
[0027] In another aspect, G is selected from the group consisting
of vinyl, styryl, acryloyloxy, and methacryloyloxy.
[0028] In another aspect, D is a divalent group selected from the
group consisting of saturated straight C.sub.1-C.sub.10
hydrocarbons, unsaturated straight C.sub.1-C.sub.10 hydrocarbons,
saturated branched C.sub.3-C.sub.10 hydrocarbons, unsaturated
branched C.sub.3-C.sub.10 hydrocarbons, saturated cyclic
C.sub.3-C.sub.10 hydrocarbons, unsaturated cyclic C.sub.3-C.sub.10
hydrocarbons, and alkyloxy substituents. Preferably, D is a
saturated straight C.sub.1-C.sub.10 hydrocarbon divalent group.
[0029] In one embodiment, a hydrophilic aromatic-based monomer of
the present invention has a formula
##STR00001##
wherein R is hydrogen or CH.sub.3; D is a divalent group selected
from the group consisting of saturated straight C.sub.1-C.sub.10
hydrocarbons, unsaturated straight C.sub.1-C.sub.10 hydrocarbons,
saturated branched C.sub.3-C.sub.10 hydrocarbons, unsaturated
branched C.sub.3-C.sub.10 hydrocarbons, saturated cyclic
C.sub.3-C.sub.10 hydrocarbons, unsaturated C.sub.3-C.sub.10
hydrocarbons, and alkoxy substituents; E is selected from the group
consisting of carboxy, carboxamide, and alcohol (including
monohydric and polyhydric alcohols) substituents; and m is an
integer from 1 to, and including, 5. Preferably, m is 1 or 2.
[0030] In one embodiment, a hydrophilic aromatic-based monomer of
the present invention has a formula
##STR00002##
wherein R is either hydrogen or CH.sub.3.
[0031] In another embodiment, a hydrophilic aromatic-based monomer
of the present invention has a formula
##STR00003##
wherein R is hydrogen or CH.sub.3.
[0032] In still another embodiment, a hydrophilic aromatic-based
monomer of the present invention has a formula
##STR00004##
wherein R.sup.1 is --C(O)O--NH.sub.2 or
--C(O)--N(CH.sub.3).sub.2.
[0033] Hydrophilic, aromatic-based monomers of the present
invention can be used to produce homopolymers or copolymers having
high refractive indices, such as about 1.4 or greater. In some
embodiments, the homopolymers or copolymers have refractive indices
in the range from about 1.4 to about 1.7; in some other
embodiments, from about 1.45 to about 1.6.
[0034] Alternatively, a hydrophilic, aromatic-based monomer of the
present invention can be copolymerized with another hydrophilic or
hydrophobic monomer to provide a polymer having high refractive
index, such as about 1.4 or greater.
[0035] Non-limiting examples of other hydrophilic monomers useful
for polymerization with one or more hydrophilic, aromatic-based
monomers of the present invention include N,N-dimethylacrylamide,
glycerol methacrylate, N-vinylpyrrolidone, and 2-hydroxyethyl
methacrylate. Preferably, N,N-dimethylacrylamide is used for
increased hydrophilicity.
[0036] Non-limiting examples of other hydrophobic monomers useful
for polymerization with one or more hydrophilic, aromatic-based
monomers of the present invention include C.sub.1-C.sub.10 alkyl
methacrylates (e.g., methyl methacrylate, ethyl methacrylate,
propyl methacrylate, butyl methacrylate, octyl methacrylate, or
2-ethylhexyl methacrylate; preferably, methyl methacrylate to
control mechanical properties), C.sub.1-C.sub.10 alkyl acrylates
(e.g., methyl acrylate, ethyl acrylate, propyl acrylate, or hexyl
acrylate; preferably, ethyl acrylate to control mechanical
properties), C.sub.6-C.sub.40 arylalkyl acrylates (e.g.,
phenylethyl acrylate, benzyl acrylate, 3-phenylpropyl acrylate,
4-phenylbutyl acrylate, 5-phenylpentyl acrylate, 8-phenyloctyl
acrylate, or 2-phenylethoxy acrylate; preferably, 2-phenylethyl
acrylate to increase refractive index), and C.sub.6-C.sub.40
arylalkyl methacrylates (e.g., 2-phenylethyl methacrylate,
3-phenylpropyl methacrylate, 4-phenylbutyl methacrylate,
5-phenylpentyl methacrylate, 8-phenyloctyl methacrylate,
2-phenoxyethyl methacrylate, 3,3-diphenylpropyl methacrylate,
2-(1-naphthylethyl)methacrylate, benzyl methacrylate, or
2-(2-naphthylethyl)methacrylate; preferably, phenylethyl
methacrylate to increase refractive index). Other suitable
hydrophobic monomers include silicon-containing monomers,
especially aromatic-based silicon-containing monomer, such as
3-methacryloyloxypropyldiphenylmethylsilane.
[0037] The hydrophilic, aromatic-based monomer having Formula (III)
can be produced by a method illustrated in Scheme 1.
##STR00005##
[0038] The hydrophilic, aromatic-based monomer having Formula (IV)
can be produced by a method illustrated in Scheme 2.
##STR00006##
[0039] Homopolymers of hydrophilic, aromatic-based monomers of the
present invention and copolymers comprising one or more
hydrophilic, aromatic-based monomers of the present invention and
at least another monomer can be produced by free radical
polymerization. For example, a copolymer of the hydrophilic,
aromatic-based monomer having Formula (III) and 2-phenylethyl
methacrylate (or 2-phenylethyl acrylate) is produced according to
the following reaction, in the presence of a thermal polymerization
initiator (such as one selected from the list of thermal
polymerization initiators disclosed below) at a temperature in the
range from about 20.degree. C. to about 120.degree. C.
Alternatively, the reaction can be carried out in the presence of a
photoinitiator selected from the list of photoinitiators disclosed
below at a temperature in the range from about 20.degree. C. to
about 60.degree. C.
##STR00007##
wherein R and R' are independently selected from the group
consisting of hydrogen and CH.sub.3; p and q are independently
selected integers greater than 1 to provide a desired molar ratio
of the monomers and a desired molecular weight. For example, p and
q can be in the range from about 1 to about 100,000, or from 1 to
about 50,000, or from 1 to 20,000.
[0040] Another exemplary copolymer comprising the monomer having
Formula (IV); N,N-dimethylacrylamide; and phenylethyl methacrylate
(or phenylethyl acrylate) is made according to the following
reaction, in the presence of a thermal polymerization initiator
(such as one selected from the list of thermal polymerization
initiators disclosed below) at a temperature in the range from
about 20.degree. C. to about 120.degree. C. Alternatively, the
reaction can be carried out in the presence of a photoinitiator
selected from the list of photoinitiators disclosed below at a
temperature in the range from about 20.degree. C. to about
60.degree. C.
##STR00008##
wherein R, R', and R'' are independently selected from the group
consisting of hydrogen and CH.sub.3; p, q, and r are independently
selected integers greater than 1 to provide a desired molar ratio
of the monomers and a desired molecular weight. For example, p, q,
and r can be in the range from about 1 to about 100,000, or from 1
to about 50,000, or from 1 to 20,000.
[0041] A formulation for the production of a polymer comprising a
hydrophilic, aromatic-based monomer of the present invention can
include one or more crosslinking agents in an amount less than
about 10 percent by weight of the weight of all monomers and
crosslinking agents, if desired. In one embodiment, the
crosslinking agents are present in an amount less than about 5
percent by weight.
[0042] Non-limiting examples of suitable crosslinking agents
include ethylene glycol dimethacrylate ("EGDMA"); diethylene glycol
dimethacrylate; ethylene glycol diacrylate; triethylene glycol
dimethacrylate; triethylene diacrylate; allyl methacrylates; allyl
acrylates; 1,3-propanediol dimethacrylate; 1,3-propanediol
diacrylate; 1,6-hexanediol dimethacrylate; 1,6-hexanediol
diacrylate; 1,4-butanediol dimethacrylate; 1,4-butanediol
diacrylate; trimethylolpropane trimethacrylate ("TMPTMA"); glycerol
trimethacrylate; poly(ethyleneoxide mono- and di-acrylate);
N,N'-dihydroxyethylene bisacrylamide; diallyl phthalate; triallyl
cyanurate; divinylbenzene; ethylene glycol divinyl ether;
N,N-methylene-bis-(meth)acrylamide; divinylbenzene; divinylsulfone;
and the like.
[0043] Although not required, homopolymers or copolymers within the
scope of the present invention may optionally have one or more
strengthening agents added prior to polymerization, preferably in
quantities of less than about 80 weight percent but more typically
from about 20 to about 60 weight percent. Non-limiting examples of
suitable strengthening agents are described in U.S. Pat. Nos.
4,327,203; 4,355,147; and 5,270,418; each of which is incorporated
herein in its entirety by reference. Specific examples, not
intended to be limiting, of such strengthening agents include
cycloalkyl acrylates and methacrylates; e.g., tert-butylcyclohexyl
methacrylate and isopropylcyclopentyl acrylate.
[0044] One or more ultraviolet ("UV") light absorbers may
optionally be added to the copolymers prior to polymerization in
quantities less than about 5 percent by weight. Suitable UV light
absorbers for use in the present invention include for example, but
are not limited to, .beta.-(4-benzotriazoyl-3-hydroxyphenoxy)ethyl
acrylate; 4-(2-acryloxyethoxy)-2-hydroxybenzophenone;
4-methacryloyloxy-2-hydroxybenzophenone;
2-(2'-methacryloyloxy-5'-methylphenyl)benzotriazole;
2-(2'-hydroxy-5'-methacryloxyethylphenyl)-2H-benzotriazole;
2-[3'-tert-butyl-2'-hydroxy-5'-(3''-methacryloyloxypropyl)phenyl]-5-chlor-
obenzotriazole;
2-(3'-tert-butyl-5'-(3''-dimethylvinylsilylpropoxy)-2'-hydroxyphenyl]-5-m-
ethoxybenzotriazole;
2-(3'-allyl-2'-hydroxy-5'-methylphenyl)benzotriazole;
2-[3'-tert-butyl-2'-hydroxy-5'-(3''-methacryloyloxypropoxy)phenyl]-5-meth-
oxybenzotriazole, and
2-[3'-tert-butyl-2'-hydroxy-5'-(3''-methacryloyloxypropoxy)phenyl]-5-chlo-
robenzotriazole. Preferably, the UV light absorber also has a
polymerizable functional group. In one embodiment, the preferred UV
light absorbers are .beta.-(4-benzotriazoyl-3-hydroxyphenoxy)ethyl
acrylate and
2-[3'-tert-butyl-2'-hydroxy-5'-(3''-methacryloyloxypropoxy)phenyl]-5-chlo-
robenzotriazole.
[0045] One or more suitable free radical polymerization initiators
may be desirably added to the copolymers of the present invention.
These initiators include thermal polymerization initiators and
photopolymerization initiators. Thermal polymerization initiators
include organic peroxy compounds and azobis(organonitrile)
compounds. Non-limiting examples of suitable organic peroxy
compounds include peroxymonocarbonate esters, such as
tert-butylperoxy isopropyl carbonate; peroxydicarbonate esters,
such as di(2-ethylhexyl) peroxydicarbonate,
di(sec-butyl)peroxydicarbonate and diisopropyl peroxydicarbonate;
diacyl peroxides, such as 2,4-dichlorobenzoyl peroxide, isobutyryl
peroxide, decanoyl peroxide, lauroyl peroxide, propionyl peroxide,
acetyl peroxide, benzoyl peroxide, p-chlorobenzoyl peroxide;
peroxyesters, such as t-butylperoxy pivalate, t-butylperoxy
octylate, and t-butylperoxy isobutyrate; methylethylketone
peroxide; and acetylcyclohexane sulfonyl peroxide. Non-limiting
examples of suitable azobis(organonitrile) compounds include
azobis(isobutyronitrile); 2,2'-azobis(2,4-dimethylpentanenitrile);
1,1'-azobiscyclohexanecarbonitrile; and
azobis(2,4-dimethylvaleronitrile); and mixtures thereof.
Preferably, such an initiator is employed in a concentration of
approximately 0.01 to 1 percent by weight of the total monomer
mixture.
[0046] Representative UV photopolymerization initiators include
those known in the field, such as the classes of benzophenone and
its derivatives, benzoin ethers, and phosphine oxides. Some
non-limiting examples of these initiators are benzophenone;
4,4'-bis(dimethylamino)benzophenone; 4,4'-dihydroxybenzophenone;
2,2-diethoxyacetophenone; 2,2-dimethoxy-2-phenylacetophenone;
4-(dimethylamino)benzophenone; 2,5-dimethylbenzophenone;
3,4-dimethybenzophenone; 4'-ethoxyacetophenone;
3'-hydroxyacetophenone; 4'-hydroxyacetophenone;
3-hydroxybenzophenone; 4-hydroxybenzophenone; 1-hydroxycyclohexyl
phenyl ketone; 2-hydroxy-2-methylpropiophenone;
2-methylbenzophenone; 3-methylbenzophenone; 4'-phenoxyacetophenone;
2-methyl-4'-(methylthio)-2-morpholinopropiophenone; benzoin methyl
ether; benzoin ethyl ether;
diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide. These initiators
are commercially available. Other photo polymerization initiators
are known under the trade names Darocur.TM. and Irgacure.TM., such
as Darocur.TM. 1173 (2-hydroxy-2-methyl-1-phenyl-1-propanone),
Irgacure.TM. 651 (2,2-dimethoxy-2-phenylacetophenone), Irgacure.TM.
819 (phenyl-bis(2,4,6-trimethyl benzoyl)phosphine oxide), and
Irgacure.TM. 184 (1-hydroxy cyclohexyl phenyl ketone) from
Ciba-Geigy, Basel, Switzerland.
[0047] The polymeric compositions of the present invention are
transparent, flexible, of relatively high refractive index and of
relatively high elongation. The polymeric compositions of the
present invention with the desirable physical properties noted
above are particularly useful in the manufacture of ophthalmic
devices such as but not limited to relatively thin, foldable IOLs,
contact lenses, corneal rings, corneal inlays, and
keratoprostheses. Furthermore, absorbed water in the polymeric
compositions of the present invention does not tend to form water
vacuoles. Thus, the polymeric compositions of the present invention
are more advantageously used in ophthalmic device applications than
prior-art acrylic compositions.
[0048] IOLs having relatively thin optic portions are critical in
enabling a surgeon to minimize surgical incision size. Keeping the
surgical incision size to a minimum reduces intraoperative trauma
and postoperative complications. A relatively thin IOL optic
portion is also critical for accommodating certain anatomical
locations in the eye such as the anterior chamber and the ciliary
sulcus. IOLs may be placed in the anterior chamber for increasing
visual acuity in either aphakic or phakic eyes, or placed in the
ciliary sulcus for increasing visual acuity in phakic eyes.
[0049] The polymeric compositions of the present invention have the
flexibility required to allow implants manufactured from the same
to be folded or deformed for insertion into an eye through the
smallest possible surgical incision, i.e., 3.5 mm or smaller.
[0050] In general, a method of making an ophthalmic device
comprises: (a) providing a polymerizable composition comprising a
hydrophilic, aromatic-based monomer of the present invention; and
(b) curing the polymerizable composition at a temperature and for a
time sufficient to produce the ophthalmic device. The curing can be
carried out such that the polymerizable composition is solidified
into the final form of the ophthalmic device or such that a solid
article is first produced and the ophthalmic device is shaped
therefrom.
[0051] In one embodiment, the method of making an ophthalmic device
comprises: (a) providing a polymerizable composition comprising a
hydrophilic, aromatic-based monomer; (b) disposing the
polymerizable composition in a mold cavity, which forms a shape of
the ophthalmic device; and (c) curing the polymerizable composition
under a condition and for a time sufficient to form the ophthalmic
device; wherein the hydrophilic, aromatic-based monomer has a
formula of
G-D-Ar (I)
wherein Ar is a C.sub.6-C.sub.24 aromatic group having at least a
hydrophilic substituent, D is a divalent linking group, and G is a
reactive functional group.
[0052] In one embodiment, at least a hydrophilic substituent on the
aromatic group is selected from the group consisting of carboxy,
carboxamide, alcohol (including monohydric and polyhydric alcohols)
substituents, and combinations thereof.
[0053] In another embodiment, at least a hydrophilic substituent on
the aromatic group is selected from the group consisting of --COOH,
--CH.sub.2--CH.sub.2OH, --(CHOH).sub.2--CH.sub.2OH,
--CH.sub.2--CHOH--CH.sub.2OH, and combinations thereof.
[0054] In still another embodiment, at least a hydrophilic
substituent on the aromatic group is a poly(alkylene glycol), such
as poly(ethylene glycol) having a formula of
--(O--CH.sub.2--CH.sub.2).sub.nOH, wherein n is an integer and
1.ltoreq.n.ltoreq.100, preferably 1.ltoreq.n.ltoreq.50, and more
preferably, 1.ltoreq.n.ltoreq.20.
[0055] In a further embodiment, said hydrophilic substituent is
selected from the group consisting of carboxamide,
dialkyl-substituted carboxamide, amino, alkanolamino, sulfonate,
phosphonate, sulfate, phosphate, ureido, substituted sugars, and
combinations thereof.
[0056] In yet another embodiment, the polymerizable composition
also comprises a crosslinking agent, or a polymerization initiator,
or both. The polymerization initiator is preferably a thermal
polymerization initiator. The curing can be carried out at an
elevated temperature such as in the range from about ambient
temperature to about 120.degree. C. In some embodiments, the curing
is carried out at a temperature from slightly higher than ambient
temperature to about 1001.degree. C. A time from about 1 minute to
about 48 hours is typically adequate for the curing.
[0057] In another embodiment, the method of making an ophthalmic
device comprises: (a) providing polymerizable composition
comprising a hydrophilic, aromatic-based monomer; (b) casting the
polymerizable composition under a condition and for a time
sufficient to form a solid block; and (c) shaping the block into
the ophthalmic device; wherein the hydrophilic, aromatic-based
monomer has a formula of
G-D-Ar (I)
wherein Ar is a C.sub.6-C.sub.24 aromatic group having at least a
hydrophilic substituent, D is a divalent linking group, and G is a
reactive functional group.
[0058] In one embodiment, said at least a hydrophilic substituent
is selected from the group consisting of carboxy, alcohols
(including monohydric and polyhydric alcohols), and combinations
thereof.
[0059] In another embodiment, at least a hydrophilic substituent on
the aromatic group is selected from the group consisting of --COOH,
--CH.sub.2--CH.sub.2OH, --(CHOH).sub.2--CH.sub.2OH,
--CH.sub.2--CHOH--CH.sub.2OH, and combinations thereof.
[0060] In still another embodiment, at least a hydrophilic
substituent on the aromatic group is a poly(alkylene glycol), such
as poly(ethylene glycol) having a formula of
--(O--CH.sub.2--CH.sub.2).sub.nOH, wherein n is an integer and
1.ltoreq.n.ltoreq.100, preferably 1.ltoreq.n.ltoreq.50, and more
preferably, 1.ltoreq.n.ltoreq.20.
[0061] In a further embodiment, said hydrophilic substituent is
selected from the group consisting of carboxamide,
dialkyl-substituted carboxamide, amino, alkanolamino, sulfonate,
phosphonate, sulfate, phosphate, ureido, substituted sugars, and
combinations thereof.
[0062] In yet another embodiment, the polymerizable composition
also comprises a crosslinking agent, or a polymerization initiator,
or both. The polymerization initiator is preferably a thermal
polymerization initiator. The casting can be carried out at an
elevated temperature such as in the range from about 20.degree. C.
to about 120.degree. C. In some embodiments, the casting is carried
out at a temperature from slightly higher than ambient temperature
to about 100.degree. C. A time from about 1 minute to about 48
hours is typically adequate for the polymerization. The shaping can
comprise cutting the solid block into wafers, and lathing or
machining the wafers into the shape of the final ophthalmic
device.
[0063] Ophthalmic medical devices manufactured using polymeric
compositions of the present invention are used as customary in the
field of opthalmology. For example, in a surgical cataract
procedure, an incision is placed in the cornea of an eye. Through
the corneal incision the cataractous natural lens of the eye is
removed (aphakic application) and an IOL is inserted into the
anterior chamber, posterior chamber or lens capsule of the eye
prior to closing the incision. However, the subject ophthalmic
devices may likewise be used in accordance with other surgical
procedures known to those skilled in the field of opthalmology.
[0064] While specific embodiments of the present invention have
been described in the foregoing, it will be appreciated by those
skilled in the art that many equivalents, modifications,
substitutions, and variations may be made thereto without departing
from the spirit and scope of the invention as defined in the
appended claims.
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