U.S. patent application number 15/179250 was filed with the patent office on 2017-02-02 for hydrophobic intraocular lens.
This patent application is currently assigned to Benz Research and Development Corporation. The applicant listed for this patent is Benz Research and Development Corporation. Invention is credited to Patrick H. Benz, Adam Reboul.
Application Number | 20170027685 15/179250 |
Document ID | / |
Family ID | 47046836 |
Filed Date | 2017-02-02 |
United States Patent
Application |
20170027685 |
Kind Code |
A1 |
Benz; Patrick H. ; et
al. |
February 2, 2017 |
HYDROPHOBIC INTRAOCULAR LENS
Abstract
An intraocular lens (IOL) with excellent non-glistening
characteristics comprising at least one copolymer comprising: (a)
one or more first monomeric subunits comprising a polymerized
acrylate and/or methacrylate group, at least one side group
comprising (i) an aryloxy moiety, and (ii) an aliphatic carbon
moiety linking the aryloxy moiety with the polymerized acrylate or
methacrylate group, wherein the aliphatic carbon moiety comprises
at least one hydroxyl substituent, (b) one or more second monomeric
subunits different from the first monomeric subunits comprising a
polymerized acrylate and/or methacrylate group, and comprising at
least one alkoxyalkyl side group, (c) one or more third monomeric
subunits different from the first and second monomeric subunits,
the third monomeric subunits comprising a polymerized acrylate
and/or methacrylate group, and comprising at least one alkylene
oxide side group, wherein the first monomeric subunit is present in
a greater amount by weight than the second monomeric subunit, and
the first and second monomeric subunits together comprise about 75
percent or more of the monomeric subunits composition by
weight.
Inventors: |
Benz; Patrick H.; (Sarasota,
FL) ; Reboul; Adam; (Sarasota, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Benz Research and Development Corporation |
Sarasota |
FL |
US |
|
|
Assignee: |
Benz Research and Development
Corporation
Sarasota
FL
|
Family ID: |
47046836 |
Appl. No.: |
15/179250 |
Filed: |
June 10, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13618894 |
Sep 14, 2012 |
9381080 |
|
|
15179250 |
|
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|
|
61535795 |
Sep 16, 2011 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C08F 220/302 20200201;
A61L 27/16 20130101; G02B 1/043 20130101; G02B 1/043 20130101; G02B
1/043 20130101; A61F 2210/0076 20130101; C08F 220/285 20200201;
C08F 220/305 20200201; C08F 220/30 20130101; C08F 220/28 20130101;
A61L 27/16 20130101; A61L 2430/16 20130101; A61F 2/16 20130101;
G02B 1/043 20130101; C08F 220/302 20200201; C08F 220/281 20200201;
C08L 33/08 20130101; C08F 220/286 20200201; C08F 222/103 20200201;
C08F 222/103 20200201; C08L 33/10 20130101; C08L 33/08 20130101;
C08F 220/286 20200201; C08F 220/281 20200201; C08L 33/08 20130101;
C08L 33/10 20130101 |
International
Class: |
A61F 2/16 20060101
A61F002/16; A61L 27/16 20060101 A61L027/16; C08F 220/30 20060101
C08F220/30 |
Claims
1.-53. (canceled)
54. A composition comprising at least one copolymer comprising: (a)
a first monomeric subunit comprising a polymerized methacrylate
group, at least one side group comprising (i) an aryloxy moiety,
and (ii) an aliphatic carbon moiety linking the aryloxy moiety with
the polymerized acrylate or methacrylate group, wherein the
aliphatic carbon moiety comprises at least one hydroxyl
substituent, and (b) a second monomeric subunit different from the
first monomeric subunit comprising a polymerized methacrylate
group, and comprising at least one alkoxyalkyl side group, (c) a
third monomeric subunit different from the first and second
monomeric subunits, the third monomeric subunits comprising a
polymerized acrylate or methacrylate group, and comprising at least
one alkylene oxide side group, wherein the first monomeric subunit
is present in a greater amount by weight than the second monomeric
subunit, and the first and second monomeric subunits together
comprise about 75 percent or more of the monomeric subunits
composition by weight.
55. The composition of claim 54, wherein the copolymer further
comprises monomeric subunits which are crosslinked subunits.
56. The composition of claim 54, wherein the copolymer further
comprises monomeric subunits which are crosslinked subunits of a
trimethacrylate crosslinker.
57. The composition of claim 54, wherein the aryloxy group
comprises a phenoxy group.
58. The composition of claim 54, wherein the aliphatic carbon
moiety of the first monomeric subunit is substituted with one
hydroxyl group.
59. The composition of claim 54, wherein the aliphatic carbon
moiety of the first monomeric subunit is represented by
--CH.sub.2--CHOH--CH.sub.2--.
60. The composition of claim 54, wherein the side group of one of
the first monomeric subunits comprises
--CH.sub.2--CHOH--CH.sub.2--OPh, wherein OPh is an unsubstituted
phenoxy group.
61. The composition of claim 54, wherein the alkoxyalkyl group
comprises 2-ethoxy ethyl.
62. The composition of claim 54, wherein the alkyleneoxide side
group is a poly(ethyleneoxide) side group.
63. The composition of claim 62, wherein the poly(ethyleneoxide)
side group has a molecular weight of 100 g/mol to 500 g/mol.
64. The composition of claim 54, further comprising a
polymerization initiator compound.
65. The composition of claim 64, wherein the polymerization
initiator compound is a UV initiator.
66. The composition of claim 54, wherein the first monomeric
subunit comprises polymerized 2-hydroxy-3-phenoxypropyl
methacrylate and the second monomeric subunit comprises
2-ethoxyethyl methacrylate.
67. The composition of claim 54, wherein the first monomeric
subunit is about 50% to about 80%, by weight of the copolymer
composition, and the second monomeric subunit is about 20% to about
35%, by weight of the copolymer composition, and the third
monomeric subunit is about 5% to about 15%, by weight of the
copolymer composition.
68. The composition of claim 54, wherein the copolymer has a glass
transition temperature below 35.degree. C.
69. An intraocular lens comprising the composition of claim 54.
70. The intraocular lens of claim 69, wherein the lens has a
central thickness of up to 1 mm and unfolds in less than or about 1
minute when placed in a saline solution at a temperature of
36.degree. C.
71. The intraocular lens of claim 69, wherein the intraocular lens
when hydrated has an SI value of less than 800.
72. A composition comprising at least one copolymer comprising: (a)
a first monomeric subunit comprising a polymerized methacrylate
group, at least one side group comprising (i) an aryloxy moiety,
and (ii) an aliphatic carbon moiety linking the aryloxy moiety with
the polymerized acrylate or methacrylate group, wherein the
aliphatic carbon moiety comprises at least one hydroxyl
substituent, and (b) a second monomeric subunit different from the
first monomeric subunit comprising a polymerized acrylate group,
and comprising at least one alkoxyalkyl side group, (c) a third
monomeric subunit different from the first and second monomeric
subunits, the third monomeric subunits comprising a polymerized
acrylate or methacrylate group, and comprising at least one
alkylene oxide side group, wherein the first monomeric subunit is
present in a greater amount by weight than the second monomeric
subunit, and the first and second monomeric subunits together
comprise about 75 percent or more of the monomeric subunits
composition by weight.
73. An intraocular lens comprising the composition of claim 72.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 13/618,894, filed Sep. 14, 2012; which claims priority to U.S.
provisional application Ser. No. 61/535,795, filed Sep. 16, 2011.
The complete disclosures of both prior applications are hereby
incorporated by reference in their entirety.
BACKGROUND
[0002] Various types of intraocular lenses (IOLs) are known. For
example, there are known one-piece intraocular lenses and composite
intraocular lens having multiple pieces. A one-piece intraocular
lens is one where both optic and non-optic portions are made from
one material. The non-optic portions of IOLs are referred to as
haptic portions, and are used for attachment purposes.
[0003] Both hydrophobic and hydrophilic foldable IOLs are described
in the prior art in, for example, U.S. Pat. Nos. 7,947,796,
7,387,642, 7,067,602, 6,517,750 and 6,267,784 each of which is
hereby incorporated by reference in its entirety. See also, for
example, U.S. Patent Publication Nos. 2008/0221235, 2006/0276606,
2006/0199929, 2005/0131183, 2002/0058724, 2002/0058723 and
2002/0027302 each of which is hereby incorporated by reference in
its entirety.
[0004] Additionally, lens materials comprising the monomer
2-hydroxy-3-phenoxypropyl acrylate are disclosed in the prior art
in, for example, WO 2010/128266, WO 2001/018079, WO 2000/079312, WO
96/40303, and U.S. Pat. No. 5,693,095. The lens material
2-ethoxyethyl methacrylate is also known in the art as a compound
with a low glass transition temperature. See, for example, Garcia,
F., et al., J. of Polymer Science: Part A: Polymer Chemistry, Vol.
40, 3987-4001 (2002).
[0005] A need exists, however, for better IOL materials including
hydrophobic materials, which do not suffer from excessive
glistening, can provide an absence of stickiness characteristics
after injection of the IOL, and can provide for
difficult-to-achieve combinations of properties.
SUMMARY
[0006] Embodiments described herein include, for example,
copolymers, lenses, intraocular lenses, blanks for intraocular
lenses, and methods for making and methods of using compositions
and intraocular lenses.
[0007] One embodiment provides, for example, an intraocular lens
comprising at least one copolymer comprising: (a) one or more first
monomeric subunits comprising a polymerized acrylate or
methacrylate group, at least one side group comprising (i) an
aryloxy moiety, and (ii) an aliphatic carbon moiety linking the
aryloxy moiety with the polymerized acrylate or methacrylate group,
wherein the aliphatic carbon moiety comprises at least one hydroxyl
substituent, and (b) one or more second monomeric subunits
different from the first monomeric subunits comprising a
polymerized acrylate or methacrylate group, and comprising at least
one alkoxyalkyl side group, (c) one or more third monomeric
subunits different from the first and second monomeric subunits,
the third monomeric subunits comprising a polymerized acrylate or
methacrylate group, and comprising at least one alkylene oxide side
group, wherein the first monomeric subunit is present in a greater
amount by weight than the second monomeric subunit, and the first
and second monomeric subunits together comprise about 75 percent or
more of the monomeric subunits composition by weight.
[0008] A composition comprising at least one copolymer comprising:
(a) one or more first monomeric subunits comprising a polymerized
acrylate or methacrylate group, at least one side group comprising
(i) an aryloxy moiety, and (ii) an aliphatic carbon moiety linking
the aryloxy moiety with the polymerized acrylate or methacrylate
group, wherein the aliphatic carbon moiety comprises at least one
hydroxyl substituent, and (b) one or more second monomeric subunits
different from the first monomeric subunits comprising a
polymerized acrylate or methacrylate group, and comprising at least
one alkoxyalkyl side group, (c) one or more third monomeric
subunits different from the first and second monomeric subunits,
the third monomeric subunits comprising a polymerized acrylate or
methacrylate group, and comprising at least one alkylene oxide side
group, wherein the first monomeric subunit is present in a greater
amount by weight than the second monomeric subunit, and the first
and second monomeric subunits together comprise about 75 percent or
more of the monomeric subunits composition by weight.
[0009] A method for making a composition comprising at least one
copolymer comprising monomeric subunits comprising: preparing a
co-monomer mixture comprising: (a) one or more first monomers
comprising a polymerizable acrylate or methacrylate group, at least
one side group comprising (i) an aryloxy moiety, and (ii) an
aliphatic carbon moiety linking the aryloxy moiety with the
polymerizable acrylate or methacrylate group, wherein the aliphatic
carbon moiety comprises at least one hydroxyl substituent, and (b)
one or more second monomers different from the first monomer(s)
comprising a polymerizable acrylate or methacrylate group, and
comprising at least one alkoxyalkyl side group, (c) one or more
third monomers different from the first and second monomers, the
third monomers comprising a polymerizable acrylate or methacrylate
group, and comprising at least one alkylene oxide side group,
wherein the first monomer(s) is present in a greater amount by
weight than the second monomer(s), and the first and second
monomers together comprise about 75 percent or more of the monomers
by weight; polymerizing the co-monomer mixture.
[0010] An intraocular lens comprising at least one copolymer
consisting essentially of: (a) one or more first monomeric subunits
consisting essentially of a polymerized acrylate or methacrylate
group, at least one side group comprising (i) an aryloxy moiety,
and (ii) an aliphatic carbon moiety linking the aryloxy moiety with
the polymerized acrylate or methacrylate group, wherein the
aliphatic carbon moiety consists essentially of at least one
hydroxyl substituent, and (b) one or more second monomeric subunits
different from the first monomeric subunits consisting essentially
of a polymerized acrylate or methacrylate group, and consisting
essentially of at least one alkoxyalkyl side group, (c) one or more
third monomeric subunits different from the first and second
monomeric subunits, the third monomeric subunits consisting
essentially of a polymerized acrylate and/or methacrylate group,
and consisting essentially of at least one alkylene oxide side
group, (d) one or more fourth monomeric subunits different from the
first, second, and third monomeric subunits which are crosslinked
subunits, wherein the first monomeric subunit is present in a
greater amount by weight than the second monomeric subunit, and the
first and second monomeric subunits together consist essentially of
about 75 percent or more of the monomeric subunits composition by
weight.
[0011] A composition comprising a co-monomer mixture comprising:
(a) one or more first monomers comprising a polymerizable acrylate
or methacrylate group, at least one side group comprising (i) an
aryloxy moiety, and (ii) an aliphatic carbon moiety linking the
aryloxy moiety with the polymerizable acrylate or methacrylate
group, wherein the aliphatic carbon moiety comprises at least one
hydroxyl substituent, and (b) one or more second monomers different
from the first monomer(s) comprising a polymerizable acrylate or
methacrylate group, and comprising at least one alkoxyalkyl side
group, (c) one or more third monomers different from the first and
second monomers, the third monomers comprising a polymerizable
acrylate or methacrylate group, and comprising at least one
alkylene oxide side group, wherein the first monomer(s) is present
in a greater amount by weight than the second monomer(s), and the
first and second monomers together comprise about 75 percent or
more of the monomers by weight.
[0012] At least one advantage for at least one embodiment includes
excellent non-glistening properties for an IOL, particularly for a
hydrophobic IOL.
[0013] At least one additional advantage for at least one
embodiment includes good unfolding properties for an IOL. For
example, an IOL embodied herein may unfold in five to ten
seconds.
[0014] At least one additional advantage for at least one
embodiment includes an absence of stickiness characteristics after
injection of the IOL (e.g., the haptic does not stick to the
optic).
[0015] At least one additional advantage for at least one
embodiment includes a refractive index of greater than 1.50 in
combination with very low glistening.
[0016] Yet another advantage for at least one embodiment is a high
diopter IOL able to pass through a small orifice injector, such as
a 1.8 mm or lower Medicel injector.
BRIEF DESCRIPTION OF THE FIGURES
[0017] FIG. 1A is a top view of an intraocular lens having a
plate-shaped haptic.
[0018] FIG. 1B is a side view of the intraocular lens having a
plate-shaped haptic shown in FIG. 1A.
[0019] FIG. 2A is a top view of an intraocular lens having a
C-shaped haptic.
[0020] FIG. 2B is a side view of the intraocular lens having a
C-shaped haptic shown in FIG. 2A.
[0021] FIG. 3A is a top view of an intraocular lens universal
blank.
[0022] FIG. 3B is a side view of an intraocular lens universal
blank shown in FIG. 3A.
[0023] FIG. 4 shows the stress relaxation of several hydrophilic
and hydrophobic IOL materials (25.degree. C.) at 1500 Pa, including
an embodiment of the present invention as HF2.
DETAILED DESCRIPTION
Introduction
[0024] All references cited herein are incorporated by reference in
their entirety.
[0025] Intraocular lens are generally known in the art. See, for
example, U.S. Pat. Nos. 7,947,796; 7,387,642; 7,067,602; 6,517,750;
and 6,267,784.
[0026] One embodiment provides an intraocular lens comprising at
least one copolymer comprising a series of monomeric subunits
including, for example: (a) one or more first monomeric subunits
comprising a polymerized acrylate or methacrylate group, at least
one side group comprising (i) an aryloxy moiety, and (ii) an
aliphatic carbon moiety linking the aryloxy moiety with the
polymerized acrylate or methacrylate group, wherein the aliphatic
carbon moiety comprises at least one hydroxyl substituent, and (b)
one or more second monomeric subunits different from the first
monomeric subunits comprising a polymerized acrylate or
methacrylate group, and comprising at least one alkoxyalkyl side
group, and (c) one or more third monomeric subunits different from
the first and second monomeric subunits, the third monomeric
subunits comprising a polymerized acrylate or methacrylate group,
and comprising at least one alkylene oxide side group, wherein the
first monomeric subunit is present in a greater amount by weight
than the second monomeric subunit, and the first and second
monomeric subunits together comprise about 75 percent or more of
the monomeric subunits composition by weight.
First/Primary Monomeric Subunit
[0027] The first monomeric subunit can be the monomer subunit
present in the largest amount as measured by weight percent for the
copolymer. This subunit comprises a polymerizable moiety, such as
acrylate, methacrylate, acrylamide and/or methacrylamide. The
subunit also comprises an aliphatic spacer comprising one or more
hydroxyl moieties. Finally, first monomeric subunit comprises an
optionally substituted aryl or aryloxy moiety. In another
embodiment, the one or more first monomeric subunits comprising a
polymerized acrylate or methacrylate group may instead comprise a
polymerized acrylamide or methacrylamide group that is optionally
substituted at the nitrogen by hydrogen or a C1 to C5 alkyl.
[0028] For example, aryloxyalkyl methacrylate monomers can be
represented by the formula Ar--O--R.sub.1-MA where Ar is an
optionally substituted aryl compound such as, for example, an
optionally substituted phenyl, R.sub.1 is an aliphatic spacer such
as a bivalent alkyl group and "MA" is methacrylate. Alternatively,
aryloxyalkyl acrylate monomers can be represented by the formula
Ar--O--R.sub.2-A where Ar is an optionally substituted aryl
compound such as, for example an optionally substituted phenyl,
R.sub.2 is an aliphatic spacer such as a bivalent alkyl group and
"A" is acrylate. Likewise, aryloxyalkyl acrylamide monomers can be
represented by the formula Ar--O--R.sub.3-AA where Ar is an
optionally substituted aryl compound such as, for example, an
optionally substituted phenyl, R.sub.3 is an aliphatic spacer such
as a bivalent alkyl group and "AA" is acrylamide. In addition,
aryloxyalkyl methacrylamide monomers can be represented by the
formula Ar--O--R.sub.4-MAA where Ar is an optionally substituted
aryl compound such as, for example, an optionally substituted
phenyl, R.sub.4 is an aliphatic spacer such as a bivalent alkyl
group and "MAA" is methacrylamide. The bivalent group R.sub.1,
R.sub.2, R.sub.3, and R.sub.4 may be further substituted by at
least one hydroxy group. The AA or MAA monomers can be optionally
substituted at the nitrogen by hydrogen or a C1 to C5 alkyl.
Examples of C1 to C5 alkyl include methyl, ethyl, propyl, butyl,
pentyl, and isomers thereof.
[0029] Both hydroxy-substituted aryloxyalkyl methacrylates and
hydroxy-substituted aryloxyalkyl acrylates are ester-containing
monomer compounds as will be recognized by those skilled in the
art. Likewise, those skilled in the art would recognize
hydroxy-substituted aryloxyalky acrylamides and hydroxy-substituted
aryloxyalky methacrylamides as amide-containing monomer compounds.
In some embodiments, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 can be
independently selected from hydroxy-substituted alkyl groups having
1 to 5 carbon atoms and in some embodiments 1, 2, 3, 4, or 5 carbon
atoms, the alkyl group is substituted by one or more hydroxy
groups. With respect to R.sub.1, it will be understood that the
hydroxy-substituted alkyl group is bonded to the O of the Ar--O
group and is also bonded to the O atom of the MA group. Similarly,
with respect to R.sub.2, it will be understood that the
hydroxy-substituted alkyl group is bonded to the O of the Ar--O
group and is also bonded to the O atom of the A group. Similarly,
with respect to R.sub.3, it will be understood that the
hydroxy-substituted alkyl group is bonded to the O of the Ar--O
group and is also bonded to the N atom of the AA group. Similarly,
with respect to R.sub.4, it will be understood that the
hydroxy-substituted alkyl group is bonded to the O of the Ar--O
group and is also bonded to the N atom of the MAA group. The
hydroxy group may be substituted to any carbon of the alkyl group.
Hydroxy-substituted alkyl groups that may be used in accordance
with the embodiments herein include straight chain alkyl groups,
including but not limited to methyl, ethyl, propyl, butyl, and
pentyl groups, wherein at least one C--H is substituted for C--OH.
Alkyl groups may also include branched chain isomers of straight
chain alkyl groups including, but not limited to, the following,
which are provided by way of example only: --CH(CH.sub.3).sub.2,
--CH(CH.sub.3)(CH.sub.2CH.sub.3), --CH(CH.sub.2CH.sub.3).sub.2,
--C(CH.sub.3).sub.3, and the like, wherein at least one C--H is
substituted for C--OH. In some embodiments, the hydroxy-substituted
aryloxyalkyl methacrylate or hydroxy-substituted aryloxyalkyl
acrylate is selected where R.sub.1 and R.sub.2 have 1, 2, 3, or 4
carbon atoms. Specific embodiments of R.sub.1, R.sub.2, R.sub.3,
and R.sub.4 are by way of non-limiting example 1-hydroxy propyl,
2-hydroxy propyl, 3-hydroxy propyl, 2-hydroxy butyl, 3-hydroxy
butyl, 2,3-dihydroxy butyl and the like. The AA or MAA monomers
being optionally substituted at the nitrogen by hydrogen or a C1 to
C5 alkyl.
[0030] Aryloxy groups will be recognized by those skilled in the
art to include an aryl compound bonded to oxygen atom. In some
embodiments, the aryl group comprises optionally substituted phenyl
or naphthyl. In some embodiments, the aryl group may comprise one
or more heteroatoms, such as by way of non-limiting example
nitrogen or sulfur. The aryl moiety may be optionally substituted
by one or more alkyl groups including but not limited to methyl,
ethyl, propyl, butyl, and pentyl groups. The alkyl groups may be
branched chain isomers of straight chain alkyl groups. The aryl
moiety may be optionally substituted by one or more alkoxy groups
comprising an alkyl group bound to an oxygen, the alkyl group
comprising, but not limited to methyl, ethyl, propyl, butyl, and/or
pentyl groups. The alkyl groups may be branched chain isomers of
straight chain alkyl groups. Additionally the aryl moiety may be
substituted by one or more halogen groups, for example, F, Cl, Br,
and/or I.
[0031] Examples of some specific hydroxy-substituted aryloxyalkyl
methacrylate, hydroxy-substituted aryloxyalkyl acrylate,
hydroxy-substituted aryloxyalkyl methacrylamide and
hydroxy-substituted aryloxyalkyl acrylamide monomers useful for
forming the copolymers, but are not limited to,
2-hydroxy-3-phenoxypropyl acrylate, 2-hydroxy-3-phenoxypropyl
methacrylate, 2-hydroxy-3-phenoxypropyl acrylamide, and/or
2-hydroxy-3-phenoxypropyl methacrylamide.
[0032] In some embodiments, the present copolymers may also include
a first monomer that is represented by the general formula (I),
wherein R' is hydrogen or methyl, Y is O or --NR'', X is H, Cl, Br,
--CH.sub.3, or --OCH.sub.3, n is 1 to 6, R'' is hydrogen or a C1 to
C5 alkyl.
##STR00001##
[0033] In other embodiments, n is 1 or 2 and X is hydrogen and Y is
O.
[0034] Hence, one preferred embodiment provides an intraocular
lens, wherein the first monomer subunits comprise a polymerized
acrylate group. In another embodiment, the aryloxy group comprises
a phenoxy group. In yet another embodiment, the aryloxy group
comprises an unsubstituted phenoxy group. In another embodiment,
the aliphatic carbon moiety of the first monomeric subunit is
substituted with one hydroxyl group. In another embodiment, the
aliphatic carbon moiety of the first monomeric subunit is a C3
moiety. In another embodiment, the aliphatic carbon moiety of the
first monomeric subunit is represented by
--CH.sub.2--CHOH--CH.sub.2--. Finally, the side group of the first
monomeric subunit, in one embodiment, comprises
--CH.sub.2--CHOH--CH.sub.2--OPh, wherein OPh is an unsubstituted
phenoxy group.
Second Monomeric Subunit
[0035] The present copolymers may also include one or more
hydrophobic monomeric subunits that can be formed from a second
monomer different from the first monomer. Examples of such
hydrophobic monomers used to make the monomeric subunits include
alkoxyalkyl methacrylate and/or alkoxyalkyl acrylate monomers.
Alkoxyalkyl methacrylate monomers can be represented by the formula
R.sub.5--O--R.sub.6-MA where R.sub.5 and R.sub.6 are alkyl groups
and "MA" is methacrylate. Alkoxyalkyl acrylate monomers can be
represented by the formula R.sub.7--O--R.sub.8-A where R.sub.7 and
R.sub.8 are alkyl groups and "A" is acrylate. Both alkoxyalkyl
methacrylates and alkoxyalkyl acrylates are ester-containing
monomer compounds as will be recognized by those skilled in the
art. In some embodiments, R.sub.5 to R.sub.8 can be independently
selected from alkyl groups having 1 to 5 carbon atoms and in some
embodiments 1, 2, 3, 4, or 5 carbon atoms. With respect to R.sub.6,
it will be understood that the alkyl group is bonded to the O of
the R.sub.5--O group and is also bonded to the O atom of the MA
group. Similarly, with respect to R.sub.8, it will be understood
that the alkyl group is bonded to the O of the R.sub.7--O group and
is also bonded to the O atom of the A group. Alkyl groups that may
be used in accordance with the embodiments herein include straight
chain alkyl groups, including but not limited to methyl, ethyl,
propyl, butyl, and pentyl groups. Alkyl groups may also include
branched chain isomers of straight chain alkyl groups including,
but not limited to, the following, which are provided by way of
example only: --CH(CH.sub.3).sub.2,
--CH(CH.sub.3)(CH.sub.2CH.sub.3), --CH(CH.sub.2CH.sub.3).sub.2,
--C(CH.sub.3).sub.3, and the like. In some embodiments, the
alkoxyalkyl methacrylate or alkoxyalkyl acrylate is selected where
R.sub.5, to R.sub.8 have 1, 2, 3, or 4 carbon atoms. Examples of
some specific alkoxyalkyl methacrylate and alkoxyalkyl acrylate
monomers useful for forming the copolymers of the embodiments
herein include, but are not limited to, methoxyethyl methacrylate,
ethoxyethyl methacrylate, propoxyethyl methacrylate, butoxymethyl
methacrylate, methoxypropyl methacrylate, ethoxypropyl
methacrylate, propoxypropyl methacrylate, butoxypropyl
methacrylate, methoxybutyl methacrylate, ethoxybutyl methacrylate,
propoxybutyl methacrylate, butoxybutyl methacrylate, methoxyethyl
acrylate, ethoxyethyl acrylate, propoxyethyl acrylate, butoxymethyl
acrylate, methoxypropyl acrylate, ethoxypropyl acrylate,
propoxypropyl acrylate, butoxypropyl acrylate, methoxybutyl
acrylate, ethoxybutyl acrylate, propoxybutyl acrylate, and
butoxybutyl acrylate. In some preferred embodiments, the copolymer
includes ethoxyethyl methacrylate (EOEMA).
[0036] Hence, a particularly preferred embodiment provides an
intraocular lens, wherein the alkoxyalkyl group is a C3 to C12
group. In one embodiment, the alkoxyalkyl group comprises a single
oxygen atom. In a specific embodiment, the alkoxyalkyl group is
2-ethoxyethyl.
[0037] In some embodiments, a hydrophobic monomer that is not
referenced above, but known to be a monomer suitable for foldable
IOLs may be incorporated. Examples of an additional hydrophobic
monomer include, but are not limited to, alkoxyalkoxyalkyl
methacrylates such as, but not limited to, ethoxyethoxyethyl
methacrylate; alkoxyalkoxyalkyl acrylates, such as, but not limited
to ethoxyethoxyethyl acrylate; alkyl methacrylate monomers; and
combinations thereof with specific examples of alkyl methacrylate
monomers being C.sub.1 alkyl to C.sub.15 alkyl methacrylate
monomers such as, but not limited to, methyl methacrylate, ethyl
methacrylate, propyl methacrylate, butyl methacrylate, hexyl
methacrylate, lauryl methacrylate, and combinations thereof.
Third Monomeric Subunit
[0038] A third monomeric subunit can be present which is different
from the first and second monomeric subunits. The present
copolymers may also include, for example, one or more polyalkylene
glycol alkylether acrylate and/or polyalkylene glycol alkylether
methacrylate monomers including of higher molecular weight.
Examples of polyalkylene glycol alkylether acrylate and/or
polyalkylene glycol alkylether methacrylate include, for example,
polyethylene glycol monomethyl ether methacrylate monomers of
varying molecular weight. In some embodiments, the third monomer
may be polyethylene glycol monomethyl ether methacrylate (200 PEG
MW) or polyethylene glycol monomethyl ether methacrylate (400 PEG
MW). In another embodiment, polyethylene glycol monomethyl ether
methacrylate of other molecular weights may be used. Other
polyethylene glycol monomethyl ether methacrylate compositions may
be used.
[0039] Hence, a particularly preferred embodiment provides an
intraocular lens or IOL blank, wherein the alkyleneoxide side group
is a poly(alkyleneoxide) side group. In one embodiment, the
alkyleneoxide side group has a molecular weight of 100 g/mol to
2,000 g/mol. In another embodiment, the alkyleneoxide side group
has a molecular weight of 100 g/mol to 1,000 g/mol. In yet another
embodiment, the alkyleneoxide side group has a molecular weight of
100 g/mol to 500 g/mol. In one embodiment, the alkyleneoxide side
group is a poly(ethyleneoxide) side group. In one embodiment, the
third monomeric subunit consists of polymerized polyethylene glycol
monomethyl ether methacrylate with a polyethylene glycol molecular
weight of about 150 to 250. In another embodiment, the third
monomeric subunit consists of polymerized polyethylene glycol
monomethyl ether methacrylate with a polyethylene glycol molecular
weight of about 350 to 450.
Crosslinker (Fourth Monomer)
[0040] The intraocular lens can comprise a copolymer that further
comprises fourth monomeric subunits that are crosslinked subunits.
In particular, trifunctional crosslinking agents can be used to
form the crosslinked subunits. However, other di- or multi
functional crosslinking agents known in the art may also be
employed.
[0041] The copolymers can be prepared using conventional
polymerization techniques known to those in the field of polymer
chemistry. Crosslinkers may be employed in the polymerization
reaction. For example, any crosslinking or difunctional monomer,
can be used in effective amounts to give the desired crosslinking
density. For example, in a concentration range of 0 to about 10
percent, such as about 0.01 to about 4 percent, or in some
embodiments from 0.5 to 3 percent by weight, based on the weight of
the polymer. Examples of suitable crosslinking agents include
di-olefinic functional component or ethylene glycol dimethacrylate
(EGDMA). Generally, crosslinkers help to enhance the resulting
copolymer's dimensional stability.
[0042] In some embodiments, the compositions include one or more
crosslinker with three or more polymerizable functionalities (a
multi-functional crosslinking agent). An example of a
multi-functional crosslinking agent includes, but is not limited
to, trimethylol propane trimethacrylate (TMPTMA). The analogous
acrylate crosslinking agents, for example, trimethylol propane
triacrylate, may also be utilized in place of any of their
methacrylate analogs or in combination with the methacrylate
analogs. Some embodiments include two or more tri-functional
crosslinking agents or a multi-functional crosslinking agent and a
di-functional crosslinking agent known in the art or incorporated
herein by reference, such as for example EGDMA. Therefore, in some
embodiments, the copolymer compositions include EGDMA and TMPTMA.
In some such embodiments, the amount of EGDMA ranges from about
0.05 to about 0.5 or about 0.4 percent by weight based on the
weight of the dry copolymer and the amount of the TMPTMA ranges
from about 0.3 to about 1.5 percent by weight based on the weight
of the dry polymer. In some such embodiments, the amount of EGDMA
ranges from about 0.08 to about 0.25 percent by weight based on the
weight of the dry copolymer and the amount of the TMPTMA ranges
from about 0.45 to about 1.2 percent by weight based on the weight
of the dry polymer. In still other such embodiments, the amount of
EGDMA ranges from about 0.1 to about 0.2 percent by weight based on
the weight of the dry copolymer and the amount of the TMPTMA ranges
from about 0.5 to about 1.0 percent by weight based on the weight
of the dry polymer.
[0043] In one embodiment, the only crosslinker used is a
trifunctional crosslinker such as a trifunctional methacrylate
crosslinker.
[0044] Examples of specific copolymers useful in the present
embodiments are discussed in the examples where all weights are
shown in grams.
Compositions/Amounts
[0045] The copolymers described herein can include the first
monomers e.g. the hydroxy-substituted aryloxyalkyl methacrylate or
hydroxy-substituted aryloxyalkyl acrylate monomers as the major
component and the second and third monomers as the minor component,
measured by weight.
[0046] In the present copolymers, the total quantity of the one or
more of the first monomer can make up the majority of the polymer,
as measured by weight. For example, in some embodiments, the total
quantity of the combined amounts of any hydroxy-substituted
aryloxyalkyl methacrylate, hydroxy-substituted aryloxyalkyl
acrylate, hydroxy-substituted aryloxyalkyl meth acrylamide or
hydroxy-substituted aryloxyalkyl acrylamide monomer may be about 50
percent to about 80 percent by weight based on the total weight of
the polymer. Alternately, the first monomer may comprise about 60
percent to about 65 percent by weight of the polymer. While the
present claims are not limited by theory, the presence of the
hydroxy-substituted aryloxyalkyl moiety may provide a hydrophobic
copolymer subject to less glistening based on the hydroxyl
functionality, which can provide a hydrogen bond donor/acceptor
site to increase compatibility with the water.
[0047] In the present copolymers, the total quantity of the one or
more of the second monomer will make up a minority of the polymer,
as measured by weight. For example, in some embodiments, the total
quantity of the combined amounts of second monomer may be about 20
percent to about 35 percent by weight of the total weight of the
polymer. Alternately, the second monomer may comprise from about 27
percent to about 32 percent by weight of the polymer. The second
monomer is a hydrophobic monomer providing a low glass transition
temperature, such as for example EEOMA.
[0048] In the present copolymers, the total quantity of the one or
more of the third monomer will make up a minority of the polymer.
For example, in some embodiments, the total quantity of the
combined amounts of third monomer may be about 5 percent to about
15 percent by weight of the polymer. Alternately, the third monomer
may comprise about 7 percent to about 10 percent by weight of the
polymer. The third monomer has a higher molecular weight and
therefore can provide reduction of glistening by use of a smaller
number of molecules while also not substantially increasing the
T.sub.g of the final polymeric material.
[0049] In the present copolymers, the total quantity of the one or
more of the crosslinking monomer will make up a minority of the
polymer. For example, in some embodiments, the total quantity of
the combined amounts of incorporated crosslinking monomer ranges
from 0.3 percent to 1.5 percent, and in some embodiments from 0.45
percent to 1.2 percent or from 0.5 to 1.0 percent, based on the
total weight of the dry copolymer of the optic portion.
[0050] When a polymer or copolymer is said to include or contain a
monomer such as ethoxyethyl methacrylate, it will be understood
that this means that the ethoxyethyl methacrylate monomer has been
reacted and incorporated into the polymer. A monomer of the claimed
compounds may also be in the form of an oligomer that can be
polymerized into the embodied copolymeric compounds.
[0051] One exemplary polymeric composition contains about 50
percent to about 70 percent of a polymerized hydroxy-substituted
aryloxyalkyl methacrylate and/or polymerized hydroxy-substituted
aryloxyalkyl acrylate, about 20 percent to about 35 percent of a
polymerized alkoxyalkyl methacrylate and/or polymerized alkoxyalkyl
acrylate and about 5 percent to about 15 percent of a polymerized
polyethylene glycol monomethyl ether methacrylate, with the balance
of the copolymer being made up of other components, such as UV
absorbers, initiation agents and/or crosslinking agents. Another
exemplary composition contains about 60 percent to about 65 percent
of a polymerized hydroxy-substituted aryloxyalkyl methacrylate
and/or polymerized hydroxy-substituted aryloxyalkyl acrylate, about
27 percent to about 32 percent of a polymerized alkoxyalkyl
methacrylate and/or polymerized alkoxyalkyl acrylate and about 7
percent to about 10 percent of a polymerized polyethylene glycol
monomethyl ether methacrylate, with the balance of the copolymer
again being made up of other components. Another exemplary
composition contains about 65 percent to about 70 percent of a
polymerized hydroxy-substituted aryloxyalkyl methacrylate and/or
polymerized hydroxy-substituted aryloxyalkyl acrylate, about 20
percent to about 30 percent of a polymerized alkoxyalkyl
methacrylate and/or polymerized alkoxyalkyl acrylate and about 5
percent to about 15 percent of a polymerized polyethylene glycol
monomethyl ether methacrylate, with the balance of the copolymer
again being made up of other components. Another exemplary
composition contains about 50 percent to about 70 percent of
polymerized 2-hydroxy-3-phenoxypropyl acrylate, about 20 percent to
about 35 percent of a polymerized alkoxyalkyl methacrylate and/or
polymerized alkoxyalkyl acrylate and about 5 percent to about 15
percent of a polymerized polyethylene glycol monomethyl ether
methacrylate, with the balance of the copolymer again being made up
of other components. In some of these compositions, the polymerized
hydroxy-substituted aryloxyalkyl acrylate and/or polymerized
hydroxy-substituted aryloxyalkyl methacrylate may be polymerized
2-hydroxy-3-phenoxypropyl acrylate. In still other such
compositions, the polymerized alkoxyalkyl methacrylate and/or
polymerized alkoxyalkyl acrylate is polymerized 2-ethoxyethyl
methacrylate. In still other such compositions, the polymerized
polyethylene glycol monomethyl ether methacrylate monomer has a
molecular weight from about 200 to about 400. As can be seen from
these exemplary compositions, the present intraocular lens can have
a range of material components and still have the desired
characteristics.
[0052] In another embodiment, the compositions of the preceding
paragraph comprise polymerized hydroxy-substituted aryloxyalkyl
methacrylamide and/or polymerized hydroxy-substituted aryloxyalkyl
acrylamide as a first monomer in place of the polymerized
hydroxy-substituted aryloxyalkyl methacrylate and/or polymerized
hydroxy-substituted aryloxyalkyl acrylate.
[0053] In some of embodiments, the copolymer compositions of the
present embodiments consist of or consist essentially of a
copolymer formed from a hydroxy-substituted aryloxyalkyl acrylate,
an alkoxyalkyl methacrylate, polyalkylene glycol alkylether
methacrylate and one or more crosslinking agent.
[0054] In some such embodiments, the copolymer is formed from a
monomers consisting of 2-hydroxy-3-phenoxypropyl acrylate,
2-ethoxyethyl methacrylate, polyethylene glycol monomethyl ether
methacrylate, and TMPTMA.
[0055] In some embodiments, a copolymer comprises, consists
essentially of, or consists of:
[0056] (a) An incorporated hydroxy-substituted aryloxyalkyl
acrylate such as 2-hydroxy-3-phenoxypropyl acrylate in an amount of
from 50 to 80 percent;
[0057] (b) An incorporated alkoxyalkyl methacrylate and/or
alkoxyalkyl acrylate such as 2-ethoxyethyl methacrylate in an
amount of from 20 to 35 percent;
[0058] (c) An incorporated polyethylene glycol monomethyl ether
methacrylate such as PEG200M or PEG400M in an amount of from 5 to
15 percent;
[0059] (d) An incorporated functional methacrylate or acrylate
crosslinking agent such as TMPTMA in an amount ranging from 0.4 to
1 percent; and
[0060] (e) optionally, one or more optional other ingredients such
as water, one or more UV absorbing compound or monomer, a colorant,
and an antioxidant.
[0061] In an embodiment, the first and second monomeric subunits
together comprise about 70, 75, 80, 85 and/or 90 percent or more of
the monomeric subunits composition by weight.
Properties of Composition
[0062] The copolymers can have a water content of less than or
about 5 percent, or less than about 3 percent, based on the weight
of the copolymer after it is fully equilibrated in water. In some
embodiments, the copolymers have a water content at equilibrium
that ranges from at or about 1 percent to at or about 5 percent
based on the weight of the copolymer after it is fully equilibrated
in water. In other embodiments, the water content ranges from about
2 percent to about 4 percent by weight of the copolymer after it is
fully equilibrated with water.
[0063] The copolymers can possess superior mechanical and optical
properties over other materials used to make IOLs. Often, because
hydrophobic IOLs are incompatible with water, they form glistenings
caused by water droplets in the material's voids. It is applicant's
belief that the hydroxyl functionality adjacent to the aryloxy
functionality can provide a hydrogen bond donor/acceptor site to
increase compatibility with the water. The combination of a monomer
such as a hydroxy-substituted aryloxyalkyl acrylate with a
hydrophobic monomer such as an alkoxyalkyl methacrylate with a low
T.sub.g can provide materials with increased refractive index over
the prior art, which also remain foldable. Furthermore, the
additional of PEG 200 or PEG 400 can provide hydrogen-bond
acceptors that also can provide a plasticization effect so the
T.sub.g remains low. The components of present embodiments can
provide for a hydrophobic lens with low T.sub.g, reduced
glistenings and reduced stickiness providing for an IOL with
desirable and reliable unfolding times, while maintaining a high
refractive index.
[0064] The copolymers can be designed to have a wide range of
physical characteristics. In some instances, the present copolymers
can be designed to have glass transition temperatures below at or
about 35.degree. C., below at or about 30.degree. C., below at or
about 25.degree. C., such as from at or about -25.degree. C. to at
or about 35.degree. C., 30.degree. C., or 25.degree. C., from about
-5.degree. C. to about 5.degree. C., 10.degree. C., 15.degree. C.,
20.degree. C., or about 25.degree. C. or from at or about 0.degree.
C. to at or about 15.degree. C. In preferred embodiments, the glass
transition temperature will be from about -5.degree. C. to about
5.degree. C. Glass transition temperatures referred to herein may
be measured at half width at a temperature change rate of
10.degree. C./minute, or other methods known in the art. As the
present copolymers have been designed to be used as intraocular
lenses, they also typically have a high refractive index, which is
generally above about 1.40. Some of the present copolymers can have
a refractive index of 1.48 or higher. Some of the present
copolymers can have a refractive index of 1.50 or higher. Because
the present copolymers are hydrophobic, they can also have
equilibrium water contents that are about 5 percent or less, for
example 4 percent, 3 percent, 2 percent, 1 percent or less. Due to
their low water contents, the present copolymers are generally not
considered hydrogels and may be considered as hydrophobic.
Generally, the present lenses also have advantageous properties
compared to prior lenses because they have a comparable or higher
refractive index than lenses containing silicone or p-hydroxyethyl
methacrylate and are more flexible, e.g., foldable, than
hydrophobic lenses that include aromatic monomers to increase the
refractive index of the resulting polymer.
Lens
[0065] A present embodiment also provides intraocular lenses made
at least partially from the present copolymers. Such intraocular
lenses include an optic portion and one or more haptic portions.
Typically, the copolymers of the embodiments will make up part or
the entire optic portion of the intraocular lens. In some
embodiments, the optic portion of the lens will have a core made
from one of the present copolymer surrounded by different polymer
or material. Lenses in which the optic portion is made up of at
least partially of one of the present copolymers will usually also
have a haptic portion. The haptic portion can also be made of
copolymer of the embodiments or can be made of a different
material, for example another polymer.
[0066] In some embodiments, the present intraocular lens is a
one-piece lens having a soft, foldable central optic region and an
outer peripheral region (haptic-region) in which both regions are
made of the same polymer. In other embodiments, the optic and
haptic regions can be formed from different types of polymers or
materials, if desired. Some lenses can also have haptic portions
that are made up of different materials, for example where one or
more haptic portions is made from the same material as the optic
portion and other haptic portions are made of materials other than
a polymer of the embodiments. Multicomponent lenses can be made by
embedding one material in the other, concurrent extrusion
processes, solidifying the hard material about the soft material,
or forming an interpenetrating network of the rigid component into
a preformed hydrophobic core. In instances where one or more haptic
portions are made from a different material than the optic portion
of the lens, the haptic portion can be attached to the optic
portion in any manner known in the art, such as by drilling a hole
or holes in the optic portion and inserting the haptic portion.
[0067] The copolymers of the present embodiments can be designed so
that they are capable of being folded so that the intraocular lens
can be inserted into the eye of an individual through a small
incision. The haptic portion of the lens provides the required
support for the lens in the eye after insertion and unfolding of
the lens and tends to help stabilize the position of the lens after
insertion and the closure of the incision. The shape of the haptic
portion design is not particularly limited and can be any desired
configuration, for example, either a plate type or graduated
thickness spiral filaments, also known as a C-loop design.
[0068] FIGS. 1A, 1B, 2A, 2B, 3A, and 3B illustrate examples of
intraocular lenses in accordance with the present embodiments. The
figures are for illustrative purposes only and do not limit the
scope of the embodiments. For instance, the intraocular lens can be
any type of intraocular lens. In the FIGS. 1 and 2, 1 is the optic
portion of the lens, 2 is the haptic portion, and 3 is a
positioning hole. FIG. 3 provides a universal blank that provides a
lens shaped out of the mold, and requires only minimal cutting
and/or shaping from the molded polymer to be a finished IOL. One
skilled in the art of intraocular lenses understands the functions
of these portions of the intraocular lens.
[0069] The optic portion 1 can be approximately 6 mm in diameter
prior to hydration. The 6 mm diameter is fairly standard in the
art, and is generally chosen to cover the pupil in its fully
dilated state under naturally occurring conditions. However, other
sizes are possible and the present embodiments are not limited to
any particular diameter or size of intraocular lens. Furthermore,
it is not necessary that the lens optic portion be circular; it
could also be oval, square, or any other shape as desired.
[0070] The intraocular lens can further include one or more
non-optical haptic components 2 extending away from the outermost
peripheral surface of the optic portion. The haptic components can
be of any desired shape, for example, graduated spiral filaments or
flat plate sections and are used to support the lens within the
posterior chamber of the eye. Lenses having any desired design
configuration can be fabricated. Further, although two types of
haptic designs are shown in the figures, the haptics can have
configurations other than those illustrated. Should the intraocular
lens include other components besides the optical and haptic
portions, such other portions can be made of a polymer as are the
haptic and optic portions, or if desired, another material.
[0071] The intraocular lenses of the embodiments may be inserted
into the eye in known manners. For example, the intraocular lens
may be folded prior to insertion into the eye by small, thin
forceps of the type typically used by ophthalmic surgeons. After
the lens is in the targeted location, it is released to unfold. As
is well known in the art, typically the lens that is to be replaced
is removed prior to insertion of the intraocular lens. The
intraocular lens of the present embodiments can be made of a
generally physiologically inert soft polymeric material that is
capable of providing a clear, transparent, refractive lens body
even after folding and unfolding. In some embodiments, the foldable
intraocular lens of the present embodiments can be inserted into
any eye by injection whereby the mechanically compliant material is
folded and forced through a small tube such as a 1 mm to 3 mm inner
diameter tube. In one embodiment the small tube has an inner
diameter of approximately 2.0 or 1.9 or 1.8 or 1.7 or 1.6 or 1.5 mm
or less. In one embodiment the inner diameter is approximately 1.4
to 2.0 mm. In one embodiment, the inner diameter is approximately
1.8 mm, in another it is 1.6 mm. In one embodiment, the finished
IOL lens is microinjectable (e.g. able to be injected through a
small tube that has an inner diameter of approximately 1.8 mm or
1.6 mm).
Methods of Making Composition
[0072] The copolymers of the embodiments herein can be prepared
using conventional polymerization techniques known to those in the
field of polymer chemistry. Crosslinkers, also referred to as
crosslinking agents, may be employed in the polymerization
reaction. For example, any suitable crosslinking di-functional,
multi-functional monomer, or combination of these can be used in
effective amounts to give the desired crosslinking density. For
example, in a concentration range of 0.4 to about 4 percent, such
as about 0.4 to about 3 percent, or in some embodiments from 0.5 to
1.5 percent by weight, based on the weight of the polymer. Examples
of suitable crosslinking agents include di-olefinic compounds such
as ethylene glycol dimethacrylate (EGDMA) and tetraethylene glycol
dimethacrylate (TEGDMA) and other cross-linking agents such as
trimethylol propane trimethacrylate (TMPTMA) which include three or
more olefinic polymerizable functionalities. Generally,
crosslinkers help to enhance the resulting polymer's dimensional
stability.
[0073] Also, if desired an initiator can be used in the
polymerization. Any initiator commonly used in the art, such as azo
derivatives, like 2,2-azobis(2,4-dimethylvaleronitrile) and
propanenitrile,2-methyl,2,2'-azobis, can be used. The initiator may
also be a UV initiator or other type of imitator as recognized by
one skilled in the art. The initiator is used in an amount
effective for initiation purposes, and is generally present from
about 0.01 to 1.0 percent by weight, based on the weight of the
polymer.
[0074] The copolymers of the present embodiments can also include
additional monomers, such as, but not limited to, monomers that
impart ultraviolet (UV) absorption to the polymer. UV absorbing
monomers are typically aromatic compounds with olefinic
functionality. The advantageous UV absorbing compounds can be added
prior to polymerization for incorporation into the resultant
polymer, as is well known in the art. The UV absorber should
preferably be capable of polymerization into the lens matrix so as
to be stable under physiological conditions. Any monomer
copolymerizable with the described monomers can optionally be used,
so long as such monomer does not materially or adversely effect the
basic characteristics of the intraocular lens. Examples of useful
additional monomers that can used are described in U.S. Pat. No.
5,326,506, hereby incorporated by reference, directed to a
composite intraocular lens. Additionally, aryl-substituted triazole
compounds, such as for example, tris-aryl triazole compounds
described in U.S. Pat. No. 6,365,652, may be used in at low
concentrations to achieve desired UV absorbing properties. Such
optional additional monomers, preferably are present in a total
amount of not more than 10 weight percent, generally less than 5
weight percent, based on the total weight of the polymer.
[0075] As described above, it may be useful to add crosslinking
agents such as EGDMA, TEGDMA, or TMPTA, for example, to enhance the
resulting polymer's dimensional stability. It may also be
advantageous to add UV absorbing compounds with the lens monomers
prior to polymerization for incorporation into the resultant
polymer. The UV absorber should preferably be capable of
polymerization into the lens matrix so as to resist extraction
under physiologic conditions. The UV-absorbing monomer can be
present in an amount effective to give the desired UV-absorbing
properties, generally less than 4 percent by weight of the polymer,
such as from 0.01 to about 1 percent by weight of the polymer.
[0076] Examples of specific copolymers useful in the present
embodiments are included in Table 1 which are also discussed in the
examples where all weights used in the polymerization are shown in
grams with the percentage of the monomers in the polymer shown in
parenthesis based on the total of all monomers and crosslinking
agents and assuming incorporation of all monomers and crosslinkers
in the copolymers.
Formation of Intraocular Lens
[0077] The intraocular lenses of the present embodiments may be
formed by methods known in the art. For example, in an exemplary
process, the monomers that form the copolymer are polymerized into
a polymer rod, polymer blanks or discs are formed from the rod, and
then the blanks are cut, for example, by a lathe into the
intraocular lens. The rods can be made by a procedure which begins
with polymerizing, in a mold, such as in a tubular or cylindrical
mold, a mixture of initiator and monomers, to form an optically
clear soft lens body. As discussed above, it may be desirable to
incorporate cross-linking materials and ultraviolet-absorbing
compounds during polymerization or into the resultant polymer
matrix. In some embodiments, the polymer rods are then cut and
ground or otherwise machined, into blanks of the desired diameter
and thickness by lathe cutting and machine milled at temperatures
below the T.sub.g into an intraocular lens.
[0078] Generally, the composite material rod is lathe cut or ground
to a diameter 0.5 to 2.0 mm thicker than the required distance from
the center of the lens body to the furthest edge of the legs or
haptics. This rod is then cut into blanks of uniform thickness. The
blanks are ground and lapped to a diameter and thickness suitable
for lathe cutting and machine milling in the conventional manner
into the intraocular lens of the present embodiments. Because the
present copolymers may have low glass transition temperatures, the
rod or blanks may require cooling below T.sub.g prior to and/or
during cutting, lathing and/or milling.
[0079] A general description of a stepwise process for forming the
blanks into intraocular lenses is set forth in the flow chart
below. One having ordinary skill in the field of intraocular lens
manufacturing, from a review of the present specification, can make
intraocular lenses using the general knowledge in the art on
intraocular lens manufacture and the process of cryogenic
machining.
[0080] Intraocular lenses can also be made by molding the present
copolymer to form all or part of the optic portion of the lens. For
example, the present copolymer can be polymerized in a mold by a
liquid mixture of monomers and additional components, to form an
optically clear soft lens body. These molding methods can involve
molding the optics on one half of the lens, such as the anterior or
posterior portion, or fully molding the lens. When only half of the
optic portion of the lens is formed in the mold then the second
side optics can be machined, for example as discussed above. In
either of these embodiments, additional material can be molded to
allow machining of various haptic designs. The copolymer may be
optionally molded in the form of a preformed lens as known in the
art as a universal blank.
Polymer does not Comprise Components
[0081] In one embodiment, the copolymer composition does not
comprise a third monomer which is a hydrophilic, low molecular
weight monomer having a molecular weight of less than about 150
g/mol, or less than about 100 g/mol.
[0082] For example, in one embodiment, the copolymer composition
does not comprise polymerized hydroxyethylacrylate (HEA). In one
embodiment, the copolymer composition does not comprise polymerized
glycidyl methacrylate (GMA). In one embodiment, the copolymer
composition does not comprise the combination of HEA and GMA.
Applications
[0083] One application is lens, including lens adapted for the
human eye, including IOLs.
[0084] Additional embodiments are provided in the following
non-limiting working examples and contrasted with comparative
examples.
WORKING EXAMPLES
[0085] HPPA refers to 2-hydroxy-3-phenoxypropyl acrylate
[0086] EOEMA refers to 2-ethoxyethyl methacrylate
[0087] PEG200M refers to polyethylene glycol monomethyl ether
methacrylate (200 PEG MW)
[0088] PEG400M refers to polyethylene glycol monomethyl ether
methacrylate (400 PEG MW)
[0089] TMPTMA refers to trimethylol propane trimethacrylate
Example 1
[0090] 24.8 grams of HPPA were mixed with 12.2 grams of EOEMA, 3.0
grams of PEG200M, and 1.1 grams of TMPTMA. The mixture was degassed
while applying vigorous stirring. The mixture was dispensed into
molds and polymerized at 70.degree. C. for eight hours, and
post-cured at 95.degree. C. for 10 hours. The molds were allowed to
cool to room temperature. The molds were opened and the polymer
disc was removed and inspected. The polymer displayed properties
summarized in Table 1.
Example 2
[0091] 26.0 grams of HPPA were mixed with 11.0 grams of EOEMA, 3.0
grams of PEG200M, and 1.1 grams of TMPTMA. The mixture was degassed
while applying vigorous stirring. The mixture was dispensed into
molds, polymerized at 70.degree. C. for eight hours, and post-cured
at 95.degree. C. for 10 hours. The molds were allowed to cool to
room temperature. The molds were opened and the polymer disc was
removed and inspected. The polymer displayed properties summarized
in Table 1.
Example 3
[0092] 26.0 grams of HPPA were mixed with 10.0 grams of EOEMA, 4.0
grams of PEG200M, and 1.1 grams of TMPTMA. The mixture was degassed
while applying vigorous stirring. The mixture was dispensed into
molds, polymerized at 70.degree. C. for eight hours, and post-cured
at 95.degree. C. for 10 hours. The molds were allowed to cool to
room temperature. The molds were opened and the polymer disc was
removed and inspected. The polymer displayed properties summarized
in Table 1.
Example 4
[0093] 24.8 grams of HPPA were mixed with 9.2 grams of EOEMA, 6.0
grams of PEG200M, and 1.1 grams of TMPTMA. The mixture was degassed
while applying vigorous stirring. The mixture was dispensed into
molds, polymerized at 70.degree. C. for eight hours, and post-cured
at 95.degree. C. for 10 hours. The molds were allowed to cool to
room temperature. The molds were opened and the polymer disc was
removed and inspected. The polymer displayed properties summarized
in Table 1.
Example 5
[0094] 24.8 grams of HPPA were mixed with 9.2 grams of EOEMA, 6.0
grams of PEG400M, and 1.1 grams of TMPTMA. The mixture was degassed
while applying vigorous stirring. The mixture was dispensed into
molds, polymerized at 70.degree. C. for eight hours, and post-cured
at 95.degree. C. for 10 hours. The molds were allowed to cool to
room temperature. The molds were opened and the polymer disc was
removed and inspected. The polymer displayed properties summarized
in Table 1.
TABLE-US-00001 TABLE 1 Properties of Working Examples Refractive
Refractive Water Opening Opening Index at Index at Content Time at
Time at Severity Example 20.degree. C. 35.degree. C. (%) T.sub.g
(.degree. C.) 20.degree. C. (s) 35.degree. C. (s) Index 1 1.5200
1.5140 3.6 5 12 5 694 2 1.5190 1.5140 3.6 5 12 5 701 3 1.5180
1.5130 3.8 3 12 5 698 4 1.5180 1.5130 3.8 0 10 3 685 5 1.5080
1.5050 4.8 -2 10 3 735
Example 5
Shear Force Measurements
[0095] Using a precision Rheometer with a thermostat liquid cell
maintained at 25.degree. C., two commonly used hydrophilic IOL
materials (Hydrophilic HEMA/EOEMA copolymer "IOL 25" (water
content=25%) Hydrophilic HEMA/MMA copolymer and "Benz Flex" (water
content=26%)) were examined. 1500 Pa of shear force was applied for
60 seconds at a normal holding force of 5 Newtons. The results are
summarized in FIG. 4. The data shows that the IOL 25 material can
absorb more than twice the shear force (through elastic
deformation) and release it more quickly than the Benz Flex
material. A commonly used Hydrophobic IOL material of (Hydrophobic
EOEMA based copolymer "HF1.2" (Tg=4.degree. C.)) was subjected to
similar conditions and can only absorb half the force and relaxes
more slowly. HF1.2 is injectable through a 2.4-2.8 mm syringe and
has an opening time of approximately 25-30 seconds. The ability to
recover from deformation is affected by these properties. The
Hydrophobic aromatic copolymer embodied herein, such as the IOL
material of Example 1 ("HF2" (Tg=5.degree. C.)) more closely
resembles IOL 25 and releases nearly as quickly (see FIG. 4).
COMPARATIVE EXAMPLES
[0096] HPPA refers to 2-hydroxy-3-phenoxypropyl acrylate EOEMA
refers to 2-ethoxyethyl methacrylate EOEA refers to 2-ethoxyethyl
acrylate TMPTMA refers to trimethylol propane trimethacrylate HEA
refers to 2-hydroxyethyl acrylate GMA refers to glycerol
methacrylate SI refers to glistening Trattler severity index.
Comparative Example 1
[0097] 24.8 grams of HPPA were mixed with 12.4 grams of EOEMA, 2.8
grams of HEA, and 1.1 grams of TMPTMA. The mixture was degassed
while applying vigorous stirring. The mixture was dispensed into
molds and polymerized at 70.degree. C. for eight hours, and
post-cured at 95.degree. C. for 10 hours. The molds were allowed to
cool to room temperature. The molds were opened and the polymer
disc was removed and inspected. The polymer displayed a glistening
level of SI=862 on the Trattler Severity Index.
Comparative Example 2
[0098] 30.0 grams of HPPA were mixed with 7.0 grams of EOEA, 2.0
grams of HEA, 1.0 grams of GMA and 1.1 grams of TMPTMA. The mixture
was degassed while applying vigorous stirring. The mixture was
dispensed into molds and polymerized at 70.degree. C. for eight
hours, and post-cured at 95.degree. C. for 10 hours. The molds were
allowed to cool to room temperature. The molds were opened and the
polymer disc was removed and inspected. The polymer displayed a
glistening level of SI=826 on the Trattler Severity Index.
Comparative Example 3
[0099] 18.5 grams of HPPA were mixed with 18.5 grams of EOEMA, 1.0
grams of HEA, 2.0 grams of GMA and 1.1 grams of TMPTMA. The mixture
was degassed while applying vigorous stirring. The mixture was
dispensed into molds and polymerized at 70.degree. C. for eight
hours, and post-cured at 95.degree. C. for 10 hours. The molds were
allowed to cool to room temperature. The molds were opened and the
polymer disc was removed and inspected. The polymer displayed a
glistening level of SI=850 on the Trattler Severity Index.
Comparative Example 4
[0100] 26.0 grams of HPPA were mixed with 14 grams of EOEMA, and
1.1 grams of TMPTMA. The mixture was degassed while applying
vigorous stirring. The mixture was dispensed into molds and
polymerized at 70.degree. C. for eight hours, and post-cured at
95.degree. C. for 10 hours. The molds were allowed to cool to room
temperature. The molds were opened and the polymer disc was removed
and inspected. The polymer displayed a glistening level of SI=801
on the Trattler Severity Index.
Refractive Index Measurements
[0101] Refractive index may be measured by methods known in the
art. The values recited herein were measured by the following
method.
[0102] Measurements were acquired using a Atago Multiwavelength
Abbe refractometer at testing temperatures of 20.degree. C..+-.2
and 35.degree. C..+-.2. To the prism of the refractometer was
applied a drop of 1-bromonaphthalene and the flat polymer was
placed thereon and allowed to equilibrate for ten minutes. RI
values were recorded for three to five additional discs of the same
formula to achieve a dry measurement average value.
[0103] Wet readings were then carried out by hydrating the discs at
20.degree. C..+-.2 for a minimum of 24 hours. The disc is placed in
the refractometer and allowed it to equilibrate at 20.degree.
C..+-.2 for ten minutes. Measurements are then repeated at
35.degree. C..+-.2.
Water Content Measurements
[0104] A set of five discs from the same batch of polymeric
material were weighed and placed in an oven at 110.degree. C..+-.10
for at least 1.5 hours. The dry discs were then weighed. The discs
were next hydrated in saline solution for 48 hours. Next, the discs
were removed from solution, blotted dry and reweighed. The change
in weight was indicative of the water content of the IOL.
Opening Time Measurements
[0105] An IOL universal blank or a finished lens was folded with
tweezers and placed in a saline solution at 20.degree. C. The
sample was then released and the amount of time that the IOL took
to return to its original shape was recorded. The procedure was
repeated at 35.degree. C.
Severity Index Measurement
[0106] An IOL universal blank was placed in saline solution at room
temperature for 12 hours. The fully immersed IOL was then inspected
under magnification of 20.times., with an angle of 30 to 55 degrees
(can be adjusted for maximum vacuole visibility). The number, size
and density of the glistenings were calculated by visual
inspection.
[0107] As will be understood by one skilled in the art, for any and
all purposes, particularly in terms of providing a written
description, all ranges disclosed herein also encompass any and all
possible subranges and combinations of subranges thereof. Any
listed range can be easily recognized as sufficiently describing
and enabling the same range being broken down into at least equal
halves, thirds, quarters, fifths, tenths, etc. As a non-limiting
example, each range discussed herein can be readily broken down
into a lower third, middle third and upper third, etc. As will also
be understood by one skilled in the art all language such as "up
to," "at least," "greater than," "less than," "more than" and the
like include the number recited and refer to ranges which can be
subsequently broken down into subranges as discussed above. In the
same manner, all ratios disclosed herein also include all subratios
falling within the broader ratio.
[0108] One skilled in the art will also readily recognize that
where members are grouped together in a common manner, such as in a
Markush group, the present embodiments encompasses not only the
entire group listed as a whole, but each member of the group
individually and all possible subgroups of the main group.
Accordingly, for all purposes, the present embodiments encompass
not only the main group, but also the main group absent one or more
of the group members. The present embodiments also envisage the
explicit exclusion of one or more of any of the group members in
the claimed embodiments.
[0109] All references, patents and publications disclosed herein
are specifically incorporated by reference in their entireties and
for all purposes as if fully set forth in their entireties. Unless
otherwise specified, "a" or "an" means "one or more".
[0110] While preferred embodiments have been illustrated and
described, it should be understood that changes and modifications
can be made therein in accordance with ordinary skill in the art
without departing from the embodiments in its broader aspects as
defined in the following claims.
* * * * *