U.S. patent application number 09/865845 was filed with the patent office on 2003-03-20 for homopolymers containing stable elasticity inducing crosslinkers and ocular implants made therefrom.
Invention is credited to Gulati, Vijay, Liao, Xiugao.
Application Number | 20030055122 09/865845 |
Document ID | / |
Family ID | 23514930 |
Filed Date | 2003-03-20 |
United States Patent
Application |
20030055122 |
Kind Code |
A1 |
Liao, Xiugao ; et
al. |
March 20, 2003 |
Homopolymers containing stable elasticity inducing crosslinkers and
ocular implants made therefrom
Abstract
Ocular implants composed of homopolymers containing stable
elasticity inducing crosslinkers which contain rigid chemical
groups disposed between at least two polymerizable ethyleneically
unsaturated chemical groups are disclosed. These ocular implants
are stable, elastic, soft, optically clear, have high refractive
index and low-tack surfaces.
Inventors: |
Liao, Xiugao; (Irvine,
CA) ; Gulati, Vijay; (Lake Forest, CA) |
Correspondence
Address: |
OPPENHEIMER WOLFF & DONNELLY, LLP
840 Newport Center Drive, Suite 700
Newport Beach
CA
92660
US
|
Family ID: |
23514930 |
Appl. No.: |
09/865845 |
Filed: |
May 25, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09865845 |
May 25, 2001 |
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09383837 |
Aug 26, 1999 |
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6271281 |
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Current U.S.
Class: |
523/106 ;
523/113; 524/86; 623/6.11 |
Current CPC
Class: |
G02B 1/043 20130101;
C08L 33/08 20130101; C08L 33/14 20130101; A61L 27/50 20130101; A61F
2/14 20130101; A61F 2/147 20130101; A61L 2430/16 20130101; G02B
1/043 20130101; G02B 1/043 20130101; A61F 2/16 20130101 |
Class at
Publication: |
523/106 ;
523/113; 524/86; 623/6.11 |
International
Class: |
A61F 002/00; C08K
003/00; C08K 005/34; A61F 002/16 |
Claims
We claim:
1. Optical implants comprising optically clear, high refractive
index, low-tack homopolymers having a glass transition temperature
of less than about 15.degree. C. and an elongation at break of at
least 150%.
2. The optical implants of claim 1, wherein said homopolymers
comprise from about 95% to 99.5% by weight monomer and from about
0.5% to 5.0% by weight stable elasticity inducing crosslinker
having a rigid chemical group disposed between a plurality of
polymerizable, ethyleneically unsaturated chemical groups.
3. The optical implants of claim 1, wherein said optical implants
are an intraocular lens.
4. The optical implants of claim 1, wherein said intraocular lenses
have a refractive index above approximately 1.50, a shore hardness
between approximately 25-42, a glass transition temperature equal
to or below approximately 15.degree. C., an elongation at break of
approximately 150% greater, and a tensile strength of at least
approximately 250 pounds per square inch.
5. The optical implants of claim 1, wherein said intraocular lenses
have a tapering peripheral border forming an edge having a
thickness of approximately 0.5 mm, or less.
6. The optical implants of claim 1, wherein said optical implants
are a corneal implant.
7. The optical implants of claim 1, wherein said optical implants
are a corneal overlay.
8. The optical implants of claim 1, wherein said optical implants
are a phakic lens.
9. Optically clear, high refractive index, low-tack homopolymers
comprising from about 95% to 99.5% by weight monomer and from about
0.5% to 5.0% by weight stable elasticity including crosslinker
having a rigid chemical group disposed between a plurality of
polymerizable, ethyleneically unsaturated chemical groups.
10. The optically clear, high refractive index, low-tack
homopolymers of claim 9, wherein said stable elasticity inducing
crosslinker is selected from the group consisting of: diacrylates
and dimethacylates of bisphenol A ethoxylate (1 EO/phenol),
bisphenol A ethoxylate (2 EO/phenol), bisphenol A propoxylate (2
PO/phenol), bisphenol A, 2,2'-diallylbisphenol A,
bis(4-(2-acryloylethoxy)phenyl)methane,
bis(4-(2-methacryloylethoxy)ph- enyl)methane, bis(naphthol) A
ethoxylate (X EO/naphthol), bis(2-acryloylalkylphenyl)propane,
bis(2-methacryloylalkylphenyl)propane, 3,3'-(ethylenedioxy)diphenyl
A ethoxylate (X EO/phenol), and naphth-diol A ethoxylate (2X
EO/naphthalene), wherein X=1-5.
11. The optically clear, high refractive index, low-tack
homopolymers of claim 9, wherein said monomer is selected from the
group consisting of: phenoxyethylacrylate, poly (ethyleneglycol)
phenylethylacrylate, 2-phenylethyl acrylate, 3-phenylethylacrylate,
4-phenylethylacrylate and alkylacrylate derivatives.
12. Stable elasticity inducing crosslinkers having a rigid chemical
group disposed between a plurality of polymerizable ethyleneically
unsaturated chemical groups.
13. The stable elasticity inducing crosslinkers of claim 12 wherein
said rigid chemical group is selected from the group consisting of:
alkaryl, biphenyl and naphthalene groups.
14. The stability inducing crosslinkers of claim 12 wherein said
rigid chemical group is selected from the group consisting of:
bisphenol A ethoxylate (1 EO/phenol), bisphenol A ethoxylate (2
EO/phenol), bisphenol A propoxylate (2 PO/phenol), bisphenol A,
2,2'-diallylbisphenol A, bis(4-(2-acryloylethoxy)phenyl)methane,
bis(4-(2-methacryloylethoxy)pheny- l)methane, bis(naphthol) A
ethoxylate (X EO/naphthol), bis(2-acryloylalkylphenyl)propane,
bis(2-methacryloylalkylphenyl)propane,
3,3,'-(ethylenedioxy)diphenyl A ethoxylate (X EO/phenol), and
naphth-diol A ethoxylate (2X EO/naphthalene), wherein X=1-5.
15. The optically clear, high refractive index, low-tack
homopolymers of claim 9, further comprising a UV absorber.
16. The optically clear, high refractive index, low-tack
homopolymers of claim 15, wherein said UV absorber is selected from
the group consisting of: acrylate, methacrylate and vinyl
functionalized bezotriazoles and benzophenols.
17. Optically clear, high refractive index, low-tack homopolymers
having a glass transition temperature of less than about 15.degree.
C. and an elongation at break of at least 150%, said homopolymers
comprising from about 95% to 99.5% by weight monomer and from about
0.5% to 5.0% by weight stable elasticity inducing crosslinker, said
crosslinker selected from the group consisting of: diacrylates and
dimethacylates of bisphenol A ethoxylate (1 EO/phenol), bisphenol A
ethoxylate (2 EO/phenol), bisphenol A propoxylate (2 PO/phenol),
bisphenol A, 2,2'-diallylbisphenol A,
bis(4-(2-acryloylethoxy)phenyl)methane,
bis(4-(2-methacryloylethoxy)ph- enyl)methane, bis(naphthol) A
ethoxylate (X EO/naphthol), bis(2-acryloylalkylphenyl)propane,
bis(2-methacryloylalkylphenyl)propane, 3,3'-(ethylenedioxy)diphenyl
A ethoxylate (X EO/phenol), and naphth-diol A ethoxylate (2X
EO/naphthalene), wherein X=1-5.
18. Optically clear, high refractive index, low-tack homopolymers
having a glass transition temperature of less than about 15.degree.
C. and an elongation at break of at least 150%, said homopolymers
comprising from about 97.1% to 99.5% by weight monomer and from
about 0.5% to 2.9% by weight stable elasticity inducing
crosslinker, said crosslinker selected from the group consisting
of: diacrylates and dimethacylates of bisphenol A ethoxylate (1
EO/phenol), bisphenol A ethoxylate (2 EO/phenol), bisphenol A
propoxylate (2 PO/phenol), bisphenol A, 2,2'-diallylbisphenol A,
bis(4-(2-acryloylethoxy)phenyl)methane,
bis(4-(2-methacryloylethoxy)ph- enyl)methane, bis(naphthol) A
ethoxylate (X EO/naphthol), bis(2-acryloylalkylphenyl)propane,
bis(2-methacryloylalkylphenyl)propane, 3,3'-(ethylenedioxy)diphenyl
A ethoxylate (X EO/phenol), and naphth-diol A ethoxylate (2X
EO/naphthalene), wherein X=1-5.
19. Intraocular lenses formed from optically clear, high refractive
index, low-tack homopolymers comprising from about 95% to 99.5% by
weight monomer and from about 0.5% to 5.0% by weight stable
elasticity inducing crosslinker having a rigid chemical group
disposed between a plurality of polymerizable, ethyleneically
unsaturated chemical groups.
20. Intraocular lenses of claim 19 wherein said crosslinker is
selected from the group consisting of: diacrylates and
dimethacylates of bisphenol A ethoxylate (1 EO/phenol), bisphenol A
ethoxylate (2 EO/phenol), bisphenol A propoxylate (2 PO/phenol),
bisphenol A, 2,2'-diallylbisphenol A,
bis(4-(2-acryloylethoxy)phenyl)methane,
bis(4-(2-methacryloylethoxy)ph- enyl)methane, bis(naphthol) A
ethoxylate (X EO/naphthol), bis(2-acryloylalkylphenyl)propane,
bis(2-methacryloylalkylphenyl)propane, 3,3'-(ethylenedioxy)diphenyl
A ethoxylate (X EO/phenol), and naphth-diol A ethoxylate (2X
EO/naphthalene), wherein X=1-5.
21. Intraocular lenses, of claim 19 wherein said monomer is
selected from the group consisting of: phenoxyethylacrylate, poly
(ethyleneglycol) phenylethylacrylate, 2-phenylethyl acrylate,
3-phenylethylacrylate, 4-phenylethylacrylate and alkylacrylate
derivatives.
Description
FIELD OF INVENTION
[0001] The present invention broadly relates to ocular implants.
Specifically, it relates to ocular implants made from homopolymers
containing chemical crosslinkers for interlinking polymer chains.
More specifically, the present invention is directed to ocular
implants made from homopolymers containing chemical crosslinkers
having the unique ability to produce stable elasticity in these
homopolymers in conjunction with the production of other unique
combinations of chemical and physical properties. The present
invention is particularly well suited to the production of
elastomeric, soft, optically clear, high refractive index, low tack
homopolymers and to medical devices, including intraocular lenses,
corneal implants, corneal overlays, and phakic retractive lenses,
made from such homopolymers.
BACKGROUND
[0002] Generally speaking, "polymers" are commonly understood to be
any of a wide variety of synthetically produced, nonmetalic or
organic compounds which can be molded into various forms and
hardened for commercial use. They are made from high molecular
weight macromolecules produce by "polymnerizing" or chemically
lining individual chemical sub-units or "monomers." There are
essentially two types of polymers: homopolymers and copolymers.
"Homopolymers" are made up of identical, repeating monomers
chemically bonded together into polymer chains of various lengths.
"Copolymers" are made from combinations of at least two different
monomers which are polymerized to form chains of alternating
different monomers or chains where the different monomers are
randomly dispersed throughout.
[0003] There are both naturally occurring and synthetically
produced polymers. Examples of natural polymers include, among
others, proteins, polysaccharides, deoxyribose nucleic acid (DNA)
and rubber, wherein the individual monomer sub-units are,
respectively, amino acids, sugars, nucleic acids, and isoprene.
Common synthetic polymers, which include plastics and silicones,
are made from highly chemically reactive monomers including
styrenes, acrylates, silanols and many others. Synthetic polymers
have become one of the most important classes of molecules since
their invention at the turn of the twentieth century. They have had
a significant impact on every aspect of human life. However,
significant efforts are continually underway to further our
understanding of, and to advance the science of polymer chemistry.
These efforts include the development of critically needed superior
polymeric materials having presently unavailable combinations of
physical and chemical properties.
[0004] The physical and chemical properties of both homopolymers
and copolymers are dictated by the extent and the nature of polymer
chain interactions within the polymers themselves. These
interactions are, in turn, a function of the individual monomeric
sub-units' sizes, weights, charges and chemical structures. The
most important types of interactions between polymer chains are
those chemical interactions which result in what is know in the art
as "crosslinking." Crosslinking can be defined as a chemical
process which joins individual polymer chains together by forming
chemical bridges between and among the polymer chains. These
"crosslinks" lock the polymer chains together into immense single
molecules wherein the individual polymer chains can no longer slip
over or relative to one another.
[0005] There are essentially two mechanisms by which polymers can
be crosslinked. The first crosslinking method utilizes an external
energy source, such as high energy radiation or heat, to induce
interactions between chemically reactive functional groups within
the individual monomers of each polymer chain forming new chemical
bonds between the polymer chains. Polymers crosslinked using such
an external energy source must be composed of monomers that are
susceptible to such chemical reactions. Typically, such monomers
have pendent, exposed chemical functional groups (portions of the
monomer that are chemically reactive and extend away from the
polymer chain, also referred to as "residues") which are capable of
interacting with chemically compatible pendent groups on adjacent
polymer chains. One example of this type of crosslinking involves
the naturally occurring proteins found in animal skin. These
proteins are complex polymers composed of numerous different
monomers (amino acids) each containing highly reactive pendent
chemical groups including sulfur, carboxylic acid and amine
residues. As animals age, the cumulative effects of UV radiation
(sun exposure) induce crosslinking between these protein molecules,
changing the physical structure of these polymers and causing the
skin to lose its natural elasticity and to become hard and
wrinkled.
[0006] The second crosslinking mechanism utilizes the addition of
exogenous crosslinking agents (an additional multifuctional
molecule, not part of a polymer chain) in conjunction with the
application of a chemical catalyst (or "accelerator") which
promotes the reaction between the crosslinking agents and the
chemical functional groups within the polymer chains. Such chemical
reactions among polymer chains using crosslinking agents are not
limited to polymers with pendent chemical groups. Rather, this form
of chemical crosslinking works equally well with smaller monomer
sub-units (such as "isoprene" or natural rubber) in which the only
reactive functional group is a double chemical bond that is
sequestered within the linear portion of the molecule (the straight
part of the polymer chain, not extending from the macromolecule).
Therefore, the use of crosslinking agents, either alone or in
conjunction with external energy sources such as heat and
radiation, provides an extremely versatile crosslinking mechanism
which can produce profound changes in the polymer's properties.
[0007] One example of the dramatic changes that such exogenous
crosslinking agents can produce in a polymer is the "vulcanization"
of rubber. Vulcanization is the process of chemically bridging or
linking the polymer's chains of natural rubber (polyisoprene) using
elemental sulfur as the exogenous crosslinking agent. Heat and
compounds such as peroxides, metallic oxides, and chlorinated
quinones are also used to catalyze the chemical reactions between
the polyisoprene chains and the sulfur. Without vulcanization,
naturally occurring raw rubber is an extremely tacky, amorphous
mass that will not hold a shape and is easily solubilized or
dissolved by organic compounds such as gasoline, oil, and acetone.
After crosslinking the raw rubber hardens and becomes less tacky,
more resistant to cold induced hardening or heat induced softening,
and resistant to organic solvents. This crosslinked rubber can be
formed into commercial articles and products while hot and fluid,
and will retain the formed shape upon cooling. Without
crosslinking, natural rubber would not possess these beneficial
properties required for its wide range of industrial applications
including tires, shoes, electric insulators and waterproof
articles.
[0008] These crosslinking techniques are commonly employed with
both natural and synthetic polymers in order to create polymer
compounds having optimized properties for particular applications.
However, crosslinking polymers is a technically difficult process
that must be precisely controlled for good results. Crosslinking
agents can be simple inorganic compounds such as the sulfur used
for vulcanization discussed above, or can be more complex organic
compounds such as the divinyl benzene used in a wide variety of
more exotic plastics. The amount of crosslinker added, the rate at
which the crosslinking reaction is allowed to occur, and the
density of the crosslinkable chemical functional groups present on
the polymer chains all contribute to the resulting polymer's
physical and chemical properties.
[0009] Consequently, the polymer chemist is faced with a series of
difficult and conflicting choices that often result in compromises
necessary to achieve the appropriate final compounds for a given
application or purpose. Further, it is essential for the polymer
chemist to understand the exact physical and chemical properties
that are desired in the final polymer compounds before the
crosslinking chemistry and mechanisms can be selected. Often, a
process which accentuates one desirable physical property, such as
polymer hardness, will have an adverse effect on another desirable
property, such as surface tackiness or stickiness. Therefore, each
crosslinking application requires a unique polymer formulation and
an associated synthetic method for production including novel
crosslinker and monomer combinations. Thus, it can be appreciated
that the design and development of a polymer for a specific task is
a daunting challenge that can involve completely new chemical and
technological approaches.
[0010] Perhaps one of the most demanding applications for modern
polymers is in the medical field, such as the field of
ophthalmology which deals with the structure, function, repair of,
and diseases of the eye. Where damage or disease (typically
cataracts) requires the replacement of the eye's natural human
lens, a polymer lens that has a unique combination of biological
and physical properties is required. In addition to replacement
intraocular lenses (IOLs), damaged corneas may require corneal
implants or overlays. More recently, corrective medical implants
known as "phakic" lenses have been proposed intended to augment or
correct the light focusing function of the natural lens. Generally,
the polymers used to produce such lenses and ocular implants must
be optically clear, have a refractive index within the range
suitable for human vision, and be biocompatible. Moreover, such
implants must balance the competing physical properties of
elasticity and flexibility with high strength and stability.
[0011] Early IOLs made from polymers such as polymethylmethacrylate
(MMA) were rigid and required a large incision (greater than 6 mm)
in order to be inserted in the eye. This often resulted in a
protracted and uncomfortable healing process which further
stimulated the development of soft IOLs that could be folded and
inserted through a considerably smaller opening (on the order of
4.0 mm or less) in order to reduce healing time and potential
complications. However, folding an IOL for small incision
implantation, though simple in theory, has been difficult to
accomplish due to the strongly conflicting physical demands
required of the polymers used to make such medical implants.
Folding a lens for implantation significantly added to the demands
placed on the polymer compounds used by requiring polymers that
possess all of the previously mentioned attributes, optical
clarity, non-tacky surfaces, stability and biocompatibility, among
others, but by also requiring that the implant possess sufficient
flexibility for folding while being sufficiently stable to resist
damage and distortion induced by folding.
[0012] Initial attempts to find a polymeric compound that could be
suitable for use with foldable IOLs centered around silicone
monomers. Silicone polymer IOLs possessed excellent optical
clarity, a suitable refractive index range, were generally
biocompatible, and had excellent resilience. However, these lenses
were relatively stiff and difficult to fold requiring larger than
ideal incisions, special implantation tools and techniques, and
have been known to unfold with nearly explosive intensity,
potentially damaging delicate structures within the eye. Further,
silicone implants have fallen out of favor due to latent
biocompatibility concerns. As a result, a number of alternating,
non-silicone organic polymers derived from acrylate and acrylate
esters have been investigated and developed.
[0013] Many types of acrylate polymers have been used or proposed
for foldable IOL fabrication. The majority of these proposed
acrylate polymers are copolymer mixes of multiple monomers intended
to produce the desired combination of properties possessed by each
monomer component. However, the technical difficulties in making
such soft, foldable optical polymers have been numerous, greatly
slowing progress in the field. The ideal ocular implant or ocular
lens, as previously stated, must be optically clear and must remain
so for a prolonged period of time following implantation. The
refractive index must be greater than 1.50 and the lens must be
stably elastic and capable of stretching to 150% of its pre-stretch
size before breaking (elongation factor). The implant must be soft
enough to allow easy pre-insertion folding and it must have a
non-tacky surface so that the inserted lens will unfold in a
predictable manner without requiring further or difficult
manipulation.
[0014] These often competing demands are extremely difficult to
combine in a single material. For example, polymers with low tack
surfaces are often too hard and crack when folded. Conversely,
softer polymers which fold easily, are usually tacky, making them
difficult to handle and complicating implantation and post
insertion unfolding. Furthermore, the ideal ocular implant must
have a stable elastic structure that will not be damaged,
distorted, or destroyed by folding, while at the same time
retaining all of the optical qualities required to function as a
successful implant, lens, or corneal replacement. In spite of the
almost continual advances in polymer chemistry and ocular implant
design, the copolymers of the prior art have failed to yield IOLs
and ocular implants having these ideal combinations of
properties.
[0015] The majority of non-silicone polymers used for IOLs and
ocular implants have been acrylate copolymers generally containing
combinations of individual monomers in concentrations ranging from
about 20 percent to 80 percent. These copolymers have been
polymerized using a variety of techniques known in the art
including external energy sources, exogenous crosslinkers,
catalysts, and accelerators. Crosslinking, when performed, has
generally been accomplished to stabilize the polymers utilizing low
concentrations of low molecular weight diacryates, multifunctional
esters, epoxides and diols.
[0016] In contrast to these known chemical techniques and
compositions, the present inventors, have surprisingly determined
that by customizing the structural configurations of their
crosslinking agents in accordance with the teachings of the present
invention, they can produce homopolymer materials that possess
markedly superior combinations.of physical and chemical properties
that were previously unobtainable in presently available
homopolymers and copolymers. For example, lenses made from the
homopolymers of the present invention, though optically clear and
remarkably elastic, are physically stable and can be cast into very
thin cross-sectional structures that were previously available only
with significantly harder polymers.
[0017] As a result, ocular implants including IOLs can be produced
having strongly tapered peripheral borders. This is particularly
important with IOLs as the present invention now makes it possible
to manufacture stably elastic intraocular lenses having sharp
edges. As a result, cell migration between the back of the IOL and
the posterior capsule of the eye [a process that often results in
posterior capsule opacification (PCO) preventing light from
reaching the retina of the eye and possibly leading to blindness]
is believed to be significantly reduced. Prior art intraocular
lenses cast from conventional acrylate polymers cannot be
manufactured with such tapered circumferential borders having sharp
edges due to the instability of conventional "soft" polymers when
cast into such thin configurations. Consequently, patients with
IOLs made from conventional polymers may be more susceptible to
cell migration and resultant PCO.
[0018] Further, as known in the art, a common, non-invasive
surgical procedure for eliminating posterior capsule opacity is to
use a laser, such as an Yittrium Aluminum Garnet or YAG laser, to
restore the patient's vision. This procedure, known as YAG
Capsulotomy, produces an incision or hole in the opacified
posterior capsule which then allows the passage of light through to
the retina. However, a not uncommon complication of a laser
capsulotomy is lens damage that can occur if a conventional
acrylate polymer IOL is inadvertently struck by the YAG laser
during the capsulotomy. This can cause damage ranging from pitting
of the lens to complete fracturing of the lens necessitating its
surgical removal and replacement.
[0019] In contrast, IOLs made from the homopolymers of the present
invention, in addition to being less susceptible to PCO, are less
susceptible to laser damage as well. In the rare event that PCO
does occur in association with the lenses of the present invention,
it is believed that the "rubbery" consistency of the homopolymers
of the present invention will render IOLs made therefrom
significantly less susceptible to the damaging effects of YAG
lasers. Thus, pitting and cracking from misdirected lasers will be
significantly reduced. Therefore, it is believed that stably soft,
elastic IOLs manufactured from the new homopolymers of the present
invention will significantly reduce the occurrence of PCO as well
as reduce the occurrence of lens damage from laser capsulotomies,
if later required. This, in turn, will result in reduced patient
discomfort and complications and in significantly reduced medical
expenses.
[0020] A further advantage of the stable elastic homopolymers of
the present invention is their remarkably high refractive indices.
As a result, IOLs made from these homopolymers can be cast in even
thinner cross-sectional shapes than were previously available
without sacrificing their optical resolution. Thus, lenses produced
in accordance with the teachings of the present invention can be
folded into significantly smaller folded configurations, resulting
in IOLs that can be inserted into the eye through smaller incisions
(on the order of 3.2 to 4.0 mm) than IOLs made from known foldable
polymers. Therefore, it should be appreciated by those skilled in
the art that, just as the foldable silicone and acrylate polymers
of the prior art represented a significant improvement over the
hard, inflexible IOLs which preceded them, IOLs made from the
homopolymers of the present invention provide yet another
technological leap forward.
[0021] Accordingly, as will be discussed in detail herein, it is an
object of the present invention to provide stably elastic,
optically clear homopolymers crosslinked with rigid, structure
enhancing crosslinkers.
[0022] It is another object of the present invention to provide
soft, optically clear, foldable, high refractive index, IOLs that
have low tack surfaces.
[0023] It is yet another object of the present invention to provide
stably elastic IOLs having peripheral borders which taper to sharp
edges that resists tearing or breaking.
[0024] It is another object of the present invention to provide
IOLs made from "rubbery" homopolymers that are resistant to YAG
laser damage.
[0025] It is still a further object of the present invention to
provide stable elastic, foldable IOLs having sufficiently high
refractive indices such that the IOLs can be sized to enable
insertion through a truly small incision in the eye.
SUMMARY OF THE INVENTION
[0026] These and other objects are achieved by the methods,
compositions, and articles of the present invention which utilize
stable elasticity inducing crosslinkers containing rigid chemical
groups which are disposed between at least two polymerizable
ethyleneically unsaturated chemical groups to produce optically
clear, high refractive index, low-tack homopolymers. When made in
accordance with the teaching of the present invention, these
homopolymers have unique combinations of physical and chemical
properties including glass transition temperatures of equal to or
less than about 15.degree. C., refractive indices of greater than
1.50, and elongations at break of at least 150%. These stably
elastic, optically clear, high refractive index, low tack
homopolymers of the present invention are particularly well suited
for use in medical devices such as ocular implants, including
intraocular lenses (IOLs), corneal implants or overlays, and phakic
lenses.
[0027] In contrast to the prior art, IOLs made from the optically
clear, high refractive index, low tack homopolymers of the present
invention are stably elastic and can be rolled or folded without
destroying, distorting, or damaging the shape or resultant function
of the lenses. The IOLs made in accordance with the teachings of
the present invention can be cast in configurations having tapering
peripheral borders providing the stably elastic IOLs with medically
desirable sharp edges. Moreover, IOLs made in accordance with the
teachings of the present invention are thinner than known foldable
lenses and can be rolled or folded for insertion through small
incisions in the eye of approximately 3 mm or even less. Once
inserted in the eye, the low tack surfaces of the IOLs provided by
the homopolymers of the present invention permit these IOLs to
unfold naturally in a predictable manner thereby reducing the
possibility of damage to structures within the eye or of the need
for additional post insertion manipulation of the lenses by the
implanting surgeon.
[0028] Generally speaking, the monomer components of the
homopolymers of the present invention include, but are not limited
to, phenoxyethylacrylate, poly(ethylene glycol)
phenylethylacrylate, 2-phenylethylacrylate, 3-phenylethylacrylate,
4-phenylethylacrylate and alkylacrylate derivatives.
[0029] The stable elasticity inducing rigid crosslinkers of the
present invention include, but are not limited to, diacrylates and
dimethacylates of bisphenol A ethoxylate (1 EO/phenol), bisphenol A
ethoxylate (2 EO/phenol), bisphenol A propoxylate (2 PO/phenol),
bisphenol A, 2,2'-diallylbisphenol A,
bis(4-(2-acryloylethoxy)phenyl)methane,
bis(4-(2-methacryloylethoxy)phenyl)methane, bis(naphthol) A
ethoxylate (X EO/naphthol), bis(2-acryloylalkylphenyl)propane,
bis(2-methacryloylalkylp- henyl)propane,
3,3'-(ethylenedioxy)diphenyl A ethoxylate (X EO/phenol), and
naphth-diol A ethoxylate (2X EO/naphthalene), wherein X=1-5.
[0030] In one exemplary embodiment of the present invention the
novel homopolymers are formulated to contain from about 95% to
99.5% monomer in conjunction with a concentration of between
approximately 0.5 to 5.0% of the stable elasticity inducing
crosslinkers.
[0031] In another exemplary embodiment of the present invention the
homopolymers of the present invention are formulated to contain
from about 97.1% to 99.5% monomer and the stable elasticity
inducing crosslinkers are present in a concentration of between
approximately 0.5 to 2.9%.
[0032] In yet another alternative exemplary embodiment of the
present invention the uniquely stable elastic homopolymers are
utilized to produce IOLs having a glass transition point equal to
or below approximately 15.degree. C., a refractive index of
approximately 1.50 or greater, an elongation at break of at least
approximately 150%, and are optically clear. As a result, these
lenses are particularly well suited for true small incision
implantation techniques and can be inserted through an incision of
approximately 3.0 to 3.4 mm or less.
[0033] Further objects and advantages of the methods, compositions,
and articles of the present invention which provide stable
elasticity inducing crosslinkers containing rigid chemical groups
to produce optically clear, high refractive index, low-tack stable
elastic homopolymers suitable for use in medical devices, as well
as a better understanding thereof, will be afforded to those
skilled in the art from a consideration of the following detailed
description of exemplary embodiments thereof taken in conjunction
with the associated drawing.
BRIEF DESCRIPTION OF THE DRAWING
[0034] FIG. 1 is a diagrammatic representation illustrating the
structural relationship between the elasticity inducing
crosslinkers of the present invention and the monomer sub-units of
the homopolymers made in accordance with the teachings of the
present invention.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0035] The present invention provides stable elasticity inducing,
rigid crosslinkers, homopolymers made therefrom, articles and
medical devices including intraocular lenses, and associated
methods. The homopolymers of the present invention have refractive
indices of approximately 1.50 or greater, glass transition
temperatures (Tg) equal to or below approximately 15.degree. C.,
elongations at break of at least approximately 150%, tensile
strengths greater than 250 psi, and shore hardnesses of
approximately 25-45. In addition, they are stably elastic and
foldable, yet are optically clear and have low tack surfaces. The
stable elasticity inducing crosslinkers of the present invention
are multifunctional molecules such as, but not limited to,
diethyleneically unsaturated compounds containing rigid chemical
groups disposed between the unsaturated groups.
[0036] The crosslinkers of the present invention contribute to
providing the unique combinations of beneficial chemical and
physical properties available in the homopolymers produced in
accordance with the teachings of the present invention. These
inventive homopolymers are ideally suited for fabricating medical
devices, specifically ocular implants, and more specifically,
intraocular lenses (IOLs), corneal implants or overlays, and phakic
lenses. The implants made in accordance with the teachings of the
present invention can be produced such that they possess a tapering
circumference or peripheral boarder terminating in a desirably
sharp edge. Moreover, the high refractive indices of the
homopolymers of the present invention, in conjunction with the
previously unavailable combinations of other beneficial physical
and chemical properties, permit the production of IOLs thin enough
to be inserted through incisions truly on the order of 3 mm or
less, the same incision sizes as are necessary to remove the
natural human lens utilizing conventional surgical techniques such
as phacoemulsification.
[0037] As illustrated in FIG. 1, the stable elastic crosslinked
homopolymers of the present invention can be synthesized by
polymerizing a monomer 2 and then crosslinking the resulting
polymer chains with a crosslinking agent 1 having at least one
rigid chemical group. Examples of suitable rigid chemical groups
include, but are not limited to, alkaryl, biphenyl and naphthalene
groups.
[0038] The crosslinkers of the present invention have relatively
high molecular weights ranging from between approximately 300
daltons to approximately 650 daltons. Non-limiting examples of
these novel crosslinkers containing rigid structural groups
include, but are not limited to, diacrylates and dimethacylates of
bisphenol A ethoxylate (1 EO/phenol), bisphenol A ethoxylate (2
EO/phenol), bisphenol A propoxylate (2 PO/phenol), bisphenol A,
2,2'-diallylbisphenol A, bis(4-(2-acryloylethoxy)phenyl)methane,
bis(4-(2-methacryloylethoxy)pheny- l)methane, bis(naphthol) A
ethoxylate (X EO/naphthol), bis(2-acryloylalkylphenyl)propane,
bis(2-methacryloylalkylphenyl)propane, 3,3'-(ethylenedioxy)diphenyl
A ethoxylate (X EO/phenol), and naphth-diol A ethoxylate (2X
EO/naphthalene), wherein X=1-5.
[0039] The relatively high molecular weights of the stable
elasticity inducing rigid crosslinkers of the present invention
result in homopolymers having a relatively high weight percentage
of crosslinker while maintaining a low crosslinking density. This
permits the resulting homopolymers made in accordance with the
teachings of the present invention to accrue the benefits of the
crosslinker without having to introduce a crosslink density high
enough to make the polymer inflexible and brittle. One of the
benefits the stable elasticity inducing rigid crosslinkers of the
present invention impart to the homopolymers of the present
invention is enhanced hyrdophobicity, or water repulsion. This
reduces the surface tackiness of the homopolymers, a problem
commonly associated with conventional "soft" acrylic polymers which
significantly limits their utility as ocular implants by
complicating their manufacture and subsequent manipulation as well
as their post-implantation shape recovery.
[0040] The optically clear, high refractive index, low-tack, stable
elastic homopolymers of the present invention are prepared in
accordance with the teachings thereof by using the stable
elasticity inducing crosslinker disclosed herein at relatively low
concentrations of between approximately 0.5% to 5.0% to
controllably modify the chemical and physical properties of the
homopolymer. For example, these crosslinker concentrations,
generally within the expected concentrations for normal or
conventional crosslinkers, result in stably elastic homopolymers
having an elongation at break equal to or exceeding 150%. In
contrast, when the concentration of crosslinker is raised to exceed
5%, or when lower molecular weight crosslinkers are used, thus
increasing crosslinking density, the resulting homopolymers become
stiff and unfoldable.
[0041] It should be appreciated by those skilled in the art that,
prior to the present invention, the only available techniques known
to effectively produce soft, foldable polymers were to combine
significant concentrations of multiple monomers, each known to
possess its own beneficial properties as a homopolymer, into a
single copolymer that would, hopefully, manifest a desirable
combination of these multiple, individual properties.
Unfortunately, these techniques rarely produced the desired
results. For example, increasing a copolymer's softness or
elasticity by decreasing the amount of crosslinker used generally
resulted in an increase in its surface tackiness. Decreasing the
surface tackiness by increasing the crosslinker concentration
generally resulted in increasing the hardness of the copolymer
making it stiff. Further, increasing polymer softness and
elasticity generally reduced the physical stability of the
copolymer such that extreme elongations greater than 100% will
result in actual tearing and permanent distortions within the
polymer. Meanwhile, optical clarity can be affected by variations
in any of these properties. Though some in the art have tried to
substitute relatively large concentrations of what are generally
considered to be crosslinking compounds for use as one or more of
the monomers in a copolymer mix, these efforts have been
unsuccessful as well. As a result, there are very few polymeric
compounds known in the art which will exhibit such desired
combinations of properties and thus function as appropriate
materials for ocular implants and lenses.
[0042] Therefore, unlike the prior art copolymers formed of
multiple and different monomers, the individual monomers utilized
to produce the novel homopolymers of the present are those whose
homopolymers, made in accordance with the teachings of the present
invention, have a glass transition temperature (Tg) of between
approximately -40.degree. C. to +15.degree. C. Exemplary
homopolymers suitable for practicing the present invention include,
but are not limited to, phenoxyethylacrylate, poly(ethylene glycol)
phenylethylacrylate, 2-phenylethylacrylate, 3-phenylethylacrylate,
4-phenylethylacrylate and alkylacrylate derivatives. Those skilled
in the art can identify other suitable monomers utilizing the
teachings of the present invention through routine
experimentation.
[0043] In addition to the stable elasticity inducing crosslinkers
of the present invention, other components can be added to the
homopolymers within the scope and teachings of the present
invention. These can include, but are not limited to, UV absorbing
compounds and polymerization initiators. Non-limiting examples of
such additional components include known UV absorbers such as
acrylate, methacrylate and vinyl functionalized bezotriazoles and
benzophenols. Similarly, polymerization initiating compounds that
can be added to the homoploymers if desired, include, without
limitation, peroxides, peroxydiacarbonates, azo free radical
initiators such as azobisisobutyronitrile (AIBN), and UV initiators
such as Irgacure.RTM.1850, Irgacure.RTM. 369 and Darocur.RTM.1700
(these UV initiators are products of Ciba Specialty Chemicals,
Basel Switzerland).
[0044] A further understanding of the stable elasticity inducing
crosslinkers, the modified homopolymers produced therefrom, the
articles manufactured from the modified homopolymers, and the
associated methods of the present invention will be afforded to
those skilled in the art from the following non-limiting examples.
Examples 1-8 demonstrate representative materials and associated
methods for the fabrication of stably elastic, optically clear,
high refractive index, low-tack homopolymers produced in accordance
with the teachings of the present invention. Example 9 illustrates
the use of exemplary novel homopolymer materials and associated
methods for forming stable elastic, small incision IOLs in
accordance with the teachings of the present invention.
EXAMPLE 1
[0045] A mixture containing 46.5 g of ethylene glycol phenyl ether
acrylate (PEA), 3.5 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA) and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra-pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. The molds consisted of two glass plates separated by a
2.5 mm fluorosilicone o-ring gasket secured with four clamps. The
molds were filled with the monomer mixture using a double-tipped
cannula. One end of the cannula was inserted through the
fluorosilcone gasket of the mold and the other end was placed into
a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.559 with a glass transition
temperature of around 5-10.degree. C.
EXAMPLE 2
[0046] A mixture containing 47.5 g of ethylene glycol phenyl ether
acrylate (PEA), 2.5 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA), and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. As in Example 1, the molds consisted of two glass plates
separated by a 2.5 mm fluorosilicone o-ring gasket secured with
four clamps. The molds were filled with the monomer mixture using a
double-tipped cannula. One end of the cannula was inserted through
the fluorosilcone gasket of the mold and the other end was placed
into a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120' C. for an additional 8 hours. After the
polymerization process was complete, the molds were cooled to
55.degree. C. and held at this temperature for a minimum of 20
minutes. The molds were opened and the acrylic sheets were cured at
120.degree. C. for 16 hours. Potentially toxic residue remaining in
the fully cured acrylic sheet was removed prior to drying. The
acrylic sheet was soxhelted with isopropyl alcohol for 48 hours.
Following the extraction process, the acrylic sheet was removed
from the soxhelting chamber, covered and transferred to a forced
air oven and dried for 48 hours at room temperature. Next, the
partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.558 with a glass transition
temperature of around 5-10.degree. C.
EXAMPLE 3
[0047] A mixture containing 48.0 g of ethylene glycol phenyl ether
acrylate (PEA), 2.0 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA) and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra-pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. As before, the molds consisted of two glass plates
separated by a 2.5 mm fluorosilicone o-ring gasket secured with
four clamps. The molds were filled with the monomer mixture using a
double-tipped cannula. One end of the cannula was inserted through
the fluorosilcone gasket of the mold and the other end was placed
into a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.556 with a glass transition
temperature of around 5-10.degree. C.
EXAMPLE 4
[0048] A mixture containing 48.5 g of ethylene glycol phenyl ether
acrylate (PEA), 1.5 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA) and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra-pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. The molds consisted of two glass plates separated by a
2.5 mm fluorosilicone o-ring gasket secured with four clamps. The
molds were filled with the monomer mixture using a double-tipped
cannula. One end of the cannula was inserted through the
fluorosilcone gasket of the mold and the other end was placed into
a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.557 with a glass transition
temperature of around 5-10.degree. C.
EXAMPLE 5
[0049] A mixture containing 49.0 g of ethylene glycol phenyl ether
acrylate (PEA), 1.0 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA) and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra-pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. Once again, the molds consisted of two glass plates
separated by a 2.5 mm fluorosilicone o-ring gasket secured with
four clamps. The molds were filled with the monomer mixture using a
double-tipped cannula. One end of the cannula was inserted through
the fluorosilcone gasket of the mold and the other end was placed
into a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.558 with a glass transition
temperature of around 5-10.degree. C.
EXAMPLE 6
[0050] A mixture containing 47.5 g of ethylene glycol phenyl ether
acrylate (PEA), 2.5 g of bisphenol A propoxylate (2 EO/phenol)
diacrylate (BPPDA), 0.65 g of 2-(4benzoyl-3-hydroxyphenoxy)ethyl
acrylate (BHPEA) and 50 mg of azobisisobutyronitrile (AIBN) was
bubbled with ultra-pure nitrogen gas for 15 to 20 minutes and then
transferred to sheet casting molds (molds) using a cannula under
ultra-pure nitrogen gas pressure. Again, the molds consisted of two
glass plates separated by a 2.5 mm fluorosilicone o-ring gasket
secured with four clamps. The molds were filled with the monomer
mixture using a double-tipped cannula. One end of the cannula was
inserted through the fluorosilcone gasket of the mold and the other
end was placed into a flask containing the monomer mixture. The
filled molds were heated at 75.degree. C. for a minimum of 16 hours
in an oven followed by heating at 120.degree. C. for an additional
8 hours. After the polymerization process was complete, the molds
were cooled to 55.degree. C. and held at this temperature for a
minimum of 20 minutes. The molds were opened and the acrylic sheets
were cured at 120.degree. C. for 16 hours. Potentially toxic
residue remaining in the fully cured acrylic sheet was removed
prior to drying. The acrylic sheet was soxhelted with isopropyl
alcohol for 48 hours. Following the extraction process, the acrylic
sheet was removed from the soxhelting chamber, covered and
transferred to a forced air oven and dried for 48 hours at room
temperature. Next, the partially dried acrylic sheet was placed in
a vacuum oven and heated to 45.degree. C. under a reduced
atmosphere for 24 hours, then heated at 75.degree. C. for an
additional 48 hours to complete the drying process. The resulting
acrylic homopolymer was soft, had a refractive index as high as
1.558 with a glass transition temperature of around 5-10.degree.
C.
EXAMPLE 7
[0051] A mixture containing 47.5 g of ethylene glycol phenyl ether
acrylate (PEA), 2.5 g of bisphenol A dimethacrylate (BPMA), 0.65 g
of 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA) and 50 mg
of azobisisobutyronitrile (AIBN) was bubbled with ultra-pure
nitrogen gas for 15 to 20 minutes and then transferred to sheet
casting molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. Again, the molds consisted of two glass plates separated
by a 2.5 mm fluorosilicone o-ring gasket secured with four clamps.
The molds were filled with the monomer mixture using a
double-tipped cannula. One end of the cannula was inserted through
the fluorosilcone gasket of the mold and the other end was placed
into a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.556 with a glass transition
temperature of around 5-10.degree. C.
EXAMPLE 8
[0052] A mixture containing 47.5 g of ethylene glycol phenyl ether
acrylate (PEA), 2.5 g of bisphenol A ethoxylate (2 EO/phenol)
diacrylate (BPEA), 0.65 g of 2-(4-benzoyl-3-hydroxyphenoxy)ethyl
acrylate (BHPEA) and 50 mg of azobisisobutyronitrile (AIBN) was
bubbled with ultra-pure nitrogen gas for 15 to 20 minutes and then
transferred to sheet casting molds (molds) using a cannula under
ultra-pure nitrogen gas pressure. Again, the molds consisted of two
glass plates separated by a 2.5 mm fluorosilicone o-ring gasket
secured with four clamps. The molds were filled with the monomer
mixture using a double-tipped cannula. One end of the cannula was
inserted through the fluorosilcone gasket of the mold and the other
end was placed into a flask containing the monomer mixture. The
filled molds were heated at 75.degree. C. for a minimum of 16 hours
in an oven followed by heating at 120.degree. C. for an additional
8 hours. After the polymerization process was complete, the molds
were cooled to 55.degree. C. and held at this temperature for a
minimum of 20 minutes. The molds were opened and the acrylic sheets
were cured at 120.degree. C. for 16 hours. Potentially toxic
residue remaining in the fully cured acrylic sheet was removed
prior to drying. The acrylic sheet was soxhelted with isopropyl
alcohol for 48 hours. Following the extraction process, the acrylic
sheet was removed from the soxhelting chamber, covered and
transferred to a forced air oven and dried for 48 hours at room
temperature. Next, the partially dried acrylic sheet was placed in
a vacuum oven and heated to 45.degree. C. under a reduced
atmosphere for 24 hours, then heated at 75.degree. C. for an
additional 48 hours to complete the drying process. The resulting
acrylic homopolymer was soft, had a refractive index as high as
1.557 and a glass transition temperature of approximately
5-10.degree. C.
EXAMPLE 9
[0053] A mixture containing 45.0 g of ethylene glycol phenyl ether
acrylate (PEA), 5.0 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA), and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra-pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. Again, the molds consisted of two glass plates separated
by a 2.5 mm fluorosilicone o-ring gasket secured with four clamps.
The molds were filled with the monomer mixture using a
double-tipped cannula. One end of the cannula was inserted through
the fluorosilcone gasket of the mold and the other end was placed
into a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.559 and a glass transition
temperature of approximately 5-10.degree. C.
EXAMPLE 10
[0054] A mixture containing 40.0 g of ethylene glycol phenyl ether
acrylate (PEA), 10.0 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA), and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra-pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. As in Example 1, the molds consisted of two glass plates
separated by a 2.5 mm fluorosilicone o-ring gasket secured with
four clamps. The molds were filled with the monomer mixture using a
double-tipped cannula. One end of the cannula was inserted through
the fluorosilcone gasket of the mold and the other end was placed
into a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.558 and a glass transition
temperature of approximately 5-10.degree. C.
EXAMPLE 11
[0055] A mixture containing 49.5 g of ethylene glycol phenyl ether
acrylate (PEA), 0.5 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA), and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra-pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. As before, the molds consisted of two glass plates
separated by a 2.5 mm fluorosilicone o-ring gasket secured with
four clamps. The molds were filled with the monomer mixture using a
double-tipped cannula. One end of the cannula was inserted through
the fluorosilcone gasket of the mold and the other end was placed
into a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.556 and a glass transition
temperature of approximately 5-10.degree. C.
EXAMPLE 12
[0056] A mixture containing 49.75 g of ethylene glycol phenyl ether
acrylate (PEA), 0.25 g of bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate (BPDMA), 0.65 g of
2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (BHPEA), and 50 mg of
azobisisobutyronitrile (AIBN) was bubbled with ultra-pure nitrogen
gas for 15 to 20 minutes and then transferred to sheet casting
molds (molds) using a cannula under ultra-pure nitrogen gas
pressure. The molds consisted of two glass plates separated by a
2.5 mm fluorosilicone o-ring gasket secured with four clamps. The
molds were filled with the monomer mixture using a double-tipped
cannula. One end of the cannula was inserted through the
fluorosilcone gasket of the mold and the other end was placed into
a flask containing the monomer mixture. The filled molds were
heated at 75.degree. C. for a minimum of 16 hours in an oven
followed by heating at 120.degree. C. for an additional 8 hours.
After the polymerization process was complete, the molds were
cooled to 55.degree. C. and held at this temperature for a minimum
of 20 minutes. The molds were opened and the acrylic sheets were
cured at 120.degree. C. for 16 hours. Potentially toxic residue
remaining in the fully cured acrylic sheet was removed prior to
drying. The acrylic sheet was soxhelted with isopropyl alcohol for
48 hours. Following the extraction process, the acrylic sheet was
removed from the soxhelting chamber, covered and transferred to a
forced air oven and dried for 48 hours at room temperature. Next,
the partially dried acrylic sheet was placed in a vacuum oven and
heated to 45.degree. C. under a reduced atmosphere for 24 hours,
then heated at 75.degree. C. for an additional 48 hours to complete
the drying process. The resulting acrylic homopolymer was soft, had
a refractive index as high as 1.557 and a glass transition
temperature of approximately 5-10.degree. C.
1TABLE 1 A Summary of Examples 1-12. Monomer Crosslinkers Initiator
Properties No. PEA BPDMA BPMA BPEA BPPDA AIBN RI Tg (.degree. C.)
Shore A Tensile (psi) % Elongation Tear (lbf/in) 1 93.00% 7.00%
0.10% 1.558 45 295 109 69 2 95.00% 5.00% 0.10% 1.558 7.8 40 369 150
47 3 96.00% 4.00% 0.10% 1.558 36 282 157 55 4 97.00% 3.00% 0.10%
1.558 7.3 33 276 165 44 5 98.00% 2.00% 0.10% 1.557 6.2 29 255 203
52 6 95.00% 5.00% 0.10% 1.556 6.6 35 255 157 43 7 95.00% 5.00%
0.10% 1.557 26 209 175 8 95.00% 5.00% 0.10% 1.558 6.7 37 200 147 54
9 90.00% 10.00% 0.10% 1.557 51 192 80 36 10 80.00% 20.00% 0.10%
1.557 64 224 51 52 11 99.00% 1.00% 0.10% 1.556 17 196 246 37 12
99.50% 0.50% 0.10% 1.556 14 309 309 34 *PEA - Ethylene glycol
phenyl ether acrylate *BPDMA - Bisphenol A ethoxylate (2 EO/phenol)
dimethacrylate *AIBN - Azobisisobutyronitrile *BPMA - Bisphenol A
dimethacrylate *BPPDA - Bisphenol A propoxylate (2 EO/phenol)
diacrylate *The glass transition temperature of the homopolymer of
ethylene glycol phenyl ether acrylate is -22.degree. C.
EXAMPLE 13
[0057] A variety of acrylic IOLs having different dioptic powers
were made from the exemplary stably elastic, high refractive index,
low tack, optically clear homopolymers of the present invention
detailed in Examples 1-12. Each lens was formed by injection or
compression molding mixtures or pre-gels of the exemplary monomers,
crosslinkers and optional additives of the present invention at a
temperature of approximately 65.degree. C. for about 16 hours
followed by heating to approximately 120.degree. C. for an
additional 8 hours. Next, the molds were placed on a hot plate at
approximately 55.degree. C. for at least 10 minutes. Potentially
toxic residues were extracted from the finished lenses with
isopropyl alcohol under soxhelting conditions for 5 hours. Next the
lenses were cooled and air dried in a forced air oven at room
temperature for 24 hours. Final drying was accomplished in a vacuum
oven under a reduced atmosphere at 45.degree. C. for another 4
hours followed by heating the lenses at 75.degree. C. for 24 hours.
The resulting stably elastic homopolymer acrylic IOLs were soft,
had non-tacky surfaces, were easily folded or rolled and had
refractive indices ranging from about 1.556 to 1.559. Each of these
IOLs was configured as a biconvex optic lens with a 0.5 mm edge
thickness, a 0.6-1.2 mm center thickness, and a 6.0 mm diameter.
Depending on the respective center thickness, each lens provided
vision corrections ranging from 6 to 30 diopter.
[0058] In sum, it will be appreciated by those skilled in the art
that the present invention addresses the long felt need of
providing soft, stable, elastic, biocompatible, low tack, high
refractive index, optically clear materials that are well suited to
the production of medical devices including optical implants and
overlays such as IOLs, corneal implants and corneal overlays,
glaucoma shunts, contact lenses, and phakic lenses. Unlike the
prior art copolymer compounds which utilize traditional
crosslinking materials to produce soft copolymers with limited
combinations of physical properties, these previously unobtainable
combinations of desirable physical and chemical properties existing
in a single composition are produced in accordance with the
teachings of the present invention through the utilization of
unique, stable elasticity inducing crosslinker compounds to modify
acrylic homopolymers so that the resultant modified homopolymers
possess and exhibit these often conflicting combinations of
properties. The present invention not only produces these novel
compounds for the first time, but does so in a greatly simplified
manner that can be readily adapted and adjusted to produce any of a
wide variety of compounds having specific combinations of physical
and chemical properties, as desired. These compounds facilitate the
production of improved medical devices and implants that are
relatively inexpensive and easy to manufacture and manipulate
during processing and during subsequent surgical implantation
procedures as well. Moreover, they are particularly well suited for
the manufacture of improved intraocular lenses that are true small
incision lenses.
[0059] While the present invention has been described with respect
to various specific examples and embodiments, it is to be
understood that the present invention is not limited to these
specific exemplary embodiments. Rather, the present invention can
be modified by substituting additional, differing monomers and
crosslinkers to produce additional modified homopolymers within the
scope and teachings thereof. Further, differing methods can be used
to produce the homopolymers of the present invention, and the
resultant homopolymers can be configured into different articles
and devices. Thus, the present invention is limited only by the
following claims and can be variously practiced within the scope of
these claims.
* * * * *