U.S. patent application number 11/235441 was filed with the patent office on 2006-01-26 for process for making silicone intraocular lens with blue light absorption properties.
Invention is credited to Yu-Chin Lai, Dominic V. Ruscio.
Application Number | 20060020338 11/235441 |
Document ID | / |
Family ID | 34226638 |
Filed Date | 2006-01-26 |
United States Patent
Application |
20060020338 |
Kind Code |
A1 |
Lai; Yu-Chin ; et
al. |
January 26, 2006 |
Process for making silicone intraocular lens with blue light
absorption properties
Abstract
A process for producing silicone intraocular lenses (IOLs)
capable of absorbing blue light. Intraocular lenses so produced
block blue light from reaching the retina of an eye implanted with
the IOL. By blocking blue light from reaching the retina, the IOL
thereby prevents potential damage to the retina.
Inventors: |
Lai; Yu-Chin; (Pittsford,
NY) ; Ruscio; Dominic V.; (Webster, NY) |
Correspondence
Address: |
Bausch & Lomb Incorporated
One Bausch & Lomb Place
Rochester
NY
14604-2701
US
|
Family ID: |
34226638 |
Appl. No.: |
11/235441 |
Filed: |
September 26, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10657781 |
Sep 8, 2003 |
|
|
|
11235441 |
Sep 26, 2005 |
|
|
|
Current U.S.
Class: |
623/6.11 ;
427/162; 427/2.1; 623/901 |
Current CPC
Class: |
G02B 1/043 20130101;
A61L 27/54 20130101; A61L 2300/442 20130101; A61L 2430/16 20130101;
G02B 1/043 20130101; C08L 83/04 20130101 |
Class at
Publication: |
623/006.11 ;
623/901; 427/002.1; 427/162 |
International
Class: |
A61F 2/16 20060101
A61F002/16; A61L 33/00 20060101 A61L033/00; B05D 5/06 20060101
B05D005/06 |
Claims
1. A method for treating medical devices comprising: exposing a
semi-finished silicone medical device to a solution containing one
or more reactive dyes and one or more catalysts.
2. A method for treating medical devices to render said devices
capable of absorbing blue light comprising: exposing a
semi-finished silicone medical device to a solution containing one
or more reactive dyes and one or more catalysts.
3. The method of claim 1 or 2 wherein said medical device is
selected from the group consisting of contact lenses,
keratoprostheses, capsular bag extension rings, corneal inlays and
corneal rings.
4. The method of claim 1 or 2 wherein said medical device is an
intraocular lens.
5. The method of claim 1 or 2 wherein said reactive dyes having
ethylenically unsaturated groups are selected from the group
consisting of vinyl, allyl, acrylate, methacrylate, acrylamide,
methacrylamide, fumarate, maleate, itaconate, styrene and
nitrile.
6. The method of claim 1 or 2 wherein said catalysts are selected
from the group consisting of platinum
(3-3.5%)-divinyltetramethyldisiloxane complex and platinum
(3-3.5%)-cyclovinylmethylsiloxane complex.
7. The method of claim 1 or 2 wherein said catalysts is a platinum
catalyst.
8. The method of claim 1 or 2 wherein said medical device is
thermally treated at a temperature less than about 100.degree.
C.
9. The method of claim 1 or 2 wherein said medical device is
thermally treated at a temperature of about 80 to 90.degree. C.
10. The method of claim 1 or 2 wherein said medical device is
thermally treated for about 30 minutes.
11. The method of claim 1 or 2 wherein said medical device is
thermally treated for a period of time less than several hours.
12. The method of claim 1 or 2 wherein said medical device is
thermally treated for about 120 minutes or less.
13-24. (canceled)
25. A method of using the medical device produced through the
method of claim 1 or 2 comprising: implanting said medical device
surgically within an eye.
26. (canceled)
27. The method of claim 1 or 2 wherein said catalyst includes one
or more inhibitors.
28. The method of claim 1 or 2 wherein said catalyst includes one
or more inhibitors selected from the group consisting of
1,3-divinyltetramethyldisiloxane and
1,3,5,7-tetramethyl-1,3,5,7-tetravinyl cyclosiloxane.
29-47. (canceled)
Description
CROSS-REFERENCE OF RELATED APPLICATION
[0001] This application is a divisional of Ser. No. 10/657,781
filed Sep. 8, 2003.
FIELD OF THE INVENTION
[0002] The present invention relates to a process for making
silicone intraocular lenses with blue light absorption properties.
More particularly, the present invention relates to a process for
reacting a silicone intraocular lens with an ethyleneically
unsaturated yellow dye to produce an intraocular lens capable of
blocking blue light.
BACKGROUND OF THE INVENTION
[0003] Since the 1940's optical devices in the form of intraocular
lens (IOL) implants have been utilized as replacements for diseased
or damaged natural ocular lenses. In most cases, an intraocular
lens is implanted within an eye at the time of surgically removing
the diseased or damaged natural lens, such as for example, in the
case of cataracts. For decades, the preferred material for
fabricating such intraocular lens implants was poly(methyl
methacrylate), which is a rigid, glassy polymer.
[0004] Softer, more flexible IOL implants have gained in popularity
in more recent years due to their ability to be compressed, folded,
rolled or otherwise deformed. Such softer IOL implants may be
deformed prior to insertion thereof through an incision in the
cornea of an eye. Following insertion of the IOL in an eye, the IOL
returns to its original pre-deformed shape due to the memory
characteristics of the soft material. Softer, more flexible IOL
implants as just described may be implanted into an eye through an
incision that is much smaller, i.e., less than 4.0 mm, than that
necessary for more rigid IOLs, i.e., 5.5 to 7.0 mm. A larger
incision is necessary for more rigid IOL implants because the lens
must be inserted through an incision in the cornea slightly larger
than the diameter of the inflexible IOL optic portion. Accordingly,
more rigid IOL implants have become less popular in the market
since larger incisions have been found to be associated with an
increased incidence of postoperative complications, such as induced
astigmatism.
[0005] With recent advances in small-incision cataract surgery,
increased emphasis has been placed on developing soft, foldable
materials suitable for use in artificial IOL implants. Mazzocco,
U.S. Pat. No. 4,573,998, discloses a deformable intraocular lens
that can be rolled, folded or stretched to fit through a relatively
small incision. The deformable lens is inserted while it is held in
its distorted configuration, then released inside the chamber of
the eye, whereupon the elastic property of the lens causes it to
resume its molded shape. As suitable materials for the deformable
lens, Mazzocco discloses polyurethane elastomers, silicone
elastomers, hydrogel polymer compounds, organic or synthetic gel
compounds and combinations thereof.
[0006] In recent years, blue light (400-500 nm) has been recognized
as being potentially hazardous to the retina. Accordingly, yellow
dyes to block blue light have been used in foldable intraocular
lenses, in conjunction with ultraviolet light absorbers, to avoid
potential damaging effects. Freeman et al., U.S. Pat. No.
6,353,069, disclose high refractive index copolymers comprising two
or more acrylate and/or methacrylate monomers with aromatic groups.
Ophthalmic devices made of the copolymers may also include colored
dyes, such as the yellow dyes disclosed in U.S. Pat. No. 5,470,932.
Such materials exhibit sufficient strength to allow devices made of
them, such as intraocular lenses, to be folded or manipulated
without fracturing.
[0007] Because of shortcomings in the properties of many soft,
flexible materials used in the manufacture of ophthalmic devices,
such as the formation of water vacuoles or "glistenings", and low
refractive index, which requires a lens to be relatively thick in
order to provide a lens of proper refractive power, new materials
and methods of manufacturing of ophthalmic devices are needed.
SUMMARY OF THE INVENTION
[0008] Soft, foldable, high refractive index, silicone intraocular
lenses (IOLs) capable of absorbing blue light are prepared in
accordance with the present invention through a coating process
using a reactive yellow dye solution having blue light blocking
properties. The blue light absorbing IOLs produced in accordance
with the present invention protect an eye's retina from potentially
damaging blue light and thereby possibly providing protection from
macular degeneration.
[0009] Blue light blocking silicone IOLs of the present invention
are produced by exposing a semi-finished silicone IOL to an
ethyleneically unsaturated yellow dye-containing solution and
allowing the same to undergo a hydrosilation reaction. Such
production process yields silicone IOLs with blue light absorbing
properties. By absorbing blue light, the IOL serves to block blue
light from reaching and potentially damaging the retina of an eye
implanted with the IOL. Silicone IOLs so produced are transparent,
relatively high in elongation and relatively high in refractive
index.
[0010] Accordingly, it is an object of the present invention to
provide a process for the production of silicone IOLs capable of
absorbing blue light.
[0011] Another object of the present invention is to provide a
process for the production of silicone IOLs having relatively high
refractive indices and good clarity.
[0012] Another object of the present invention is to provide a
process for the production of silicone IOLs that are flexible.
[0013] Still another object of the present invention is to provide
biocompatible silicone IOLs capable of absorbing blue light.
[0014] These and other objectives and advantages of the present
invention, some of which are specifically described and others that
are not, will become apparent from the detailed description and
claims that follow.
DETAILED DESCRIPTION OF THE INVENTION
[0015] The present invention relates to a novel process for the
production of high refractive index silicone IOLs capable of
absorbing blue light and thereby blocking blue light from reaching
the retina of an eye implanted with the IOL. Silicone IOLs of the
present invention are produced by allowing a semi-finished silicone
IOL to react with an ethyleneically unsaturated dye through a
hydrosilation reaction. The subject process for treating silicone
IOLs is relatively simple and produces biocompatible silicone IOLs
capable of absorbing blue light.
[0016] A "semi-finished" silicone IOL for purposes of the present
invention, is a silicone IOL having free hydrosilyl groups. By
dipping a semi-finished silicone IOL in a weak solvent, such as for
example but not limited to methylene chloride, containing a one or
more reactive dyes, such as a reactive yellow dye, and one or more
platinum catalysts, followed by thermal treatment of the IOL in an
oven at a low temperature, preferably less than approximately
100.degree. C. for a relatively short period of time, preferably
less than several hours and more preferably less than approximately
30 minutes, a quantitative amount of dye can be incorporated into
or coat the IOL. There are several platinum catalysts or catalyst
systems suitable for the hydrosilation reaction of the present
invention, depending on the reaction temperature and kinetics
desired. For example, platinum (3 to
3.5%)-divinyltetramethyldisiloxane complex is suitable for use in a
room temperature reaction. Platinum (3 to
3.5%)-cyclovinylmethylsiloxane complex is suitable for use in a
reaction at a moderate temperature of 50 to 100.degree. C. The
reaction kinetics can be regulated through the concentration of the
catalyst and through the addition of various amounts of one or more
inhibitors. Suitable inhibitors include for example but are not
limited to 1,3-divinyltetramethyldisiloxane and
1,3,5,7-tetramethyl-1,3,5,7-tetravinyl cyclosiloxane. Such
inhibitors may be present in the catalyst complex. The chemical
reaction that takes place as a result of this process is
illustrated below in Reaction Scheme 1. ##STR1## As depicted above
in Reaction Scheme 1, Si--H represents the free hydrosilyl groups
of a "semi-finished" silicone IOL, and H.sub.2C.dbd.CR.sub.1R.sub.2
represents a reactive yellow dye. Here, R.sub.1 can be H or
CH.sub.3 and R.sub.2 is a group containing other functional groups
as well as functional groups responsible for yellow color. The
reactive yellow dye can have for example, but is not limited to the
following ethylenically unsaturated groups: vinyl, allyl, acrylate,
methacrylate, acrylamide, methacrylamide, fumarate, maleate,
itaconate, styrene, nitrile and the like. Depending on the
particular solvent and the concentration of reactive yellow dyes in
the solvent, the reactive yellow dye can penetrate into the polymer
matrix of the lens body, as well as, partially or completely coat
the lens surface.
[0017] Reactive dyes useful in the manufacture of flexible, high
refractive index silicone IOLs capable of absorbing blue light, may
be prepared through a process of multiple chemical reaction steps.
This process includes a step for forming a blue light absorbing
functional group, i.e., a dye, such as for example but not limited
to a diazo coupling for azo dye formation. The process also
includes a step to incorporate the compound with a dye functional
group and a reagent that is ethylenically unsaturated. For example,
a reactive azo yellow dye having two ethylenically unsaturated
groups can be prepared by reacting a yellow dye having two alcohol
groups with an acid chloride or an isocyanate having an
ethylenically unsaturated group. Such is depicted in Reaction
Schemes 2 through 3 wherein a yellow dye,
N,N-bis-(2-hydroxyethyl)-(4-phenylazo) aniline (Solvent Yellow 58),
synthesized in accordance with the procedure of Example 1 below, is
used as an example not intended to be limiting. ##STR2##
[0018] Here, "Ph" represents either C.sub.6H.sub.5 or
C.sub.6H.sub.4, as appropriate. ##STR3## Alternatively, a reactive
yellow dye with one ethylenically unsaturated group useful in
accordance with the present invention, such as for example but not
limited to N-2-[3'-(2''-methylphenylazo)-4'-hydroxyphenyl]ethyl
vinylacetamide, represented below in Formula 1, ##STR4## can be
prepared by first reacting vinylacetyl chloride with
4-aminoethylphenol to give 4-vinylacetamidoethyl phenol, which is
then coupled with the diazonium salt of toluidine as described in
more detail below in Example 4.
[0019] The process of the present invention for preparing flexible,
high refractive index silicone IOLs with blue light absorption
properties is described in still greater detail in the Examples
provided below.
EXAMPLE 1
Synthesis of N,N-bis-(2-hydroxyethyl)-(4-phenylazo) aniline
(Solvent Yellow 58)
[0020] The synthesis of N,N-bis-(2-hydroxyethyl)-(4-phenylazo)
aniline is accomplished by coupling the diazonium salt of aniline
with N-phenyl diethanolamine. A detailed procedure is also
described in D. L. Jinkerson, U.S. Pat. No. 5,470,932, incorporated
herein in its entirety by reference.
EXAMPLE 2
Synthesis of
N,N-bis-(2-alivicarbamatoethyl)-(4'-phenylazo)aniline
[0021] A 1000-mL 3-neck, round bottom flask connected with a reflux
condenser and a drying tube, is charged with 250 mL of methylene
chloride, 5.7 grams (0.02 mole) of
N,N-bis-(2-hydroxyethyl)-(4-phenylazo)aniline, 3.28 g of allyl
isocyanate (0.04 mole) (Aldrich Chemical, Inc., Milwaukee, Wis.)
and 0.014 g of dibutyltin dilaurate (Aldrich Chemical). The mixture
is heated and refluxed overnight under vigorous stirring. The
mixture is then checked with infrared spectroscopy and no residual
isocyanate peak is found indicating the reaction is complete. The
mixture is concentrated using a rotavapor. High performance liquid
chromatography (HPLC) analysis indicates only one major product.
The product is then passed through silica gel chromatography to
give final purified product with a yield of at least 80 percent.
The product is identified by nuclear magnetic resonance (NMR) and
Mass Spectroscopy.
EXAMPLE 3
Synthesis of
N,N-bis-(2-vinylacetoxyethyl)-(4'-Phenylazo)aniline
[0022] A 1000-mL 3-neck, round bottom flask connected with a reflux
condenser and a drying tube, is charged with 250 mL of methylene
chloride, 5.7 grams (0.02 mole) of
N,N-bis-(2-hydroxyethyl)-(4-phenylazo) aniline and 4.04 grams of
triethylamine (0.04 mole). The contents are chilled with an ice
bath. Through a dropping funnel, 4.18 g (0.04 mole) of vinylacetyl
chloride is added into the flask over a period of 30 minutes. The
ice bath is then removed and the contents are continuously stirred
overnight. The mixture is then filtered and then condensed using a
rotavapor. HPLC analysis indicates only one major product. The
product is then passed through silica gel chromatography to give a
final purified product with a yield of at least 80 percent. The
product is identified by NMR and Mass Spectroscopy.
EXAMPLE 4
Synthesis of N-2-[3'-2''-methylphenylazo)-4'-hydroxyphenyl]ethyl
vinylacetamide
[0023] N-2-[3'-(2''-methylphenylazo)-4'-hydroxyphenyl]ethyl
vinylacetamide can be made in two steps. The first step is the
formation of 4-vinylacetamidoethyl phenol. The second step is the
coupling of azonium salt of toluidine with the phenol to give the
product.
Step 1. Synthesis of 4-vinylacetamidoethyl phenol.
[0024] A 1000-mL 3-neck, round bottom flask connected with a reflux
condenser and a drying tube, is charged with 250 mL of methylene
chloride, 5.48 grams (0.04 mole) 4-aminoethylphenol and 4.04 grams
(0.04 mole) triethylamine. The contents are chilled with an ice
bath. Through a dropping funnel, 4.18 g (0.04 mole) of vinylacetyl
chloride is added into the flask over a period of 30 minutes. The
ice bath is then removed and the contents are continuously stirred
overnight. The mixture is then filtered and then condensed using a
rotavapor. High performance liquid chromatography (HPLC) analysis
indicates only one major product. The product is then passed
through silica gel chromatography to give a final purified product
with a yield of at least 80 percent. The product is identified by
NMR and Mass Spectroscopy.
Step 2. Coupling of product from Step 1 with toluidine diazonium
salt.
[0025] The procedure is about the same as that described in D. L.
Jinkerson, U.S. Pat. No. 5,470,932, Example 1, second half. The
difference is that 4-vinylacetamidoethyl phenol is used to replace
the acrylamidoethyl phenol. The product is identified by NMR and
Mass Spectroscopy.
EXAMPLE 5
Preparation of Yellow Dye Solution for Coating of an IOL
[0026] Solutions containing 0.1, 0.5, 1, 2 and 5 weight percent of
the yellow dye of Example 4 in methylene chloride are prepared. To
these solutions, platinum-cyclovinylmethylsiloxane complex (Gelest,
Inc., Tullytown, Pa.) at 1% of the weight of the yellow dye is also
added.
EXAMPLE 6
Coating of Silicone Intraocular Lenses
[0027] Ten (10) freshly thermally cured SoFlex.TM. Model L161 U
(Bausch & Lomb, Incorporated, Rochester, N.Y.) lenses are
submerged into each coating solution as described in Example 3 for
30, 60 and 120 minutes. The lenses are then removed from the
coating solutions and air dried. The lenses are then placed in an
oven at 80 to 90.degree. C. for an hour. These lenses are then
subjected to standard processing to get the final finished
product.
[0028] Model L161 U lenses are silicone IOLs derived from
components consisting of a vinyl terminated
polydimethyl-co-diphenyl siloxane, silicon-based reinforcing resins
with vinyl groups, and an oligomer with multi hydrosilane units.
Model L161 U silicone lenses have excess free hydrosilane groups
after curing.
EXAMPLE 7
Selection of Yellow Dye Concentration and Coating Conditions
[0029] Run ultraviolet (UV) and visible absorption spectroscopy of
coated lenses before and after processing. Select the yellow dye
concentration and residence time of lens in dye solution based on
the visible light absorption of the process lenses between 400-500
nm. Conditions, which give about or less than 50% transmittance and
maintenance of lens power/cosmetics are chosen for further coating
studies, followed by optimization of conditions.
[0030] Soft, foldable, relatively high refractive index of
approximately 1.42 or greater, relatively high elongation of
approximately 100 percent or greater, silicone IOLs with blue light
absorption properties are synthesized through the process of the
present invention. Suitable catalysts for use in the process of the
present invention include but are not limited to platinum
(3-3.5%)-divinyltetramethyldisiloxane complex and platinum
(3-3.5%)-cyclovinylmethylsiloxane complex.
[0031] The silicone IOLs produced as described herein have the
flexibility required to allow the same to be folded or deformed for
insertion into an eye through the smallest possible surgical
incision, i.e., 3.5 mm or smaller. It is unexpected that the
subject silicone IOLs described herein could possess the ideal
physical properties disclosed herein. The ideal physical properties
of the subject silicone IOLs are unexpected because changes in
mechanical properties such as modulus, percent elongation and tear
strength can occur upon addition of the reactive dye functional
groups.
[0032] Silicone IOLs treated using the process of the present
invention can be of any design capable of being rolled or folded
for implantation through a relatively small surgical incision,
i.e., 3.5 mm or less. Such IOLs may be manufactured to have an
optic portion and haptic portions made of the same or differing
materials. Once the material(s) are selected, the same may be cast
in molds of the desired shape, cured and removed from the molds.
After such molding, the IOLs are treated in accordance with the
process of the present invention and then cleaned, polished,
packaged and sterilized by customary methods known to those skilled
in the art.
[0033] In addition to IOLs, the process of the present invention is
also suitable for use in the production of other medical or
ophthalmic devices such as contact lenses, keratoprostheses,
capsular bag extension rings, corneal inlays, corneal rings and
like devices.
[0034] Silicone IOLs manufactured using the process of the present
invention are used as customary in the field of ophthalmology. For
example, in a surgical cataract procedure, an incision is placed in
the cornea of an eye. Through the corneal incision the cataractous
natural lens of the eye is removed (aphakic application) and an IOL
is inserted into the anterior chamber, posterior chamber or lens
capsule of the eye prior to closing the incision. However, the
subject ophthalmic devices may likewise be used in accordance with
other surgical procedures known to those skilled in the field of
ophthalmology.
[0035] While there is shown and described herein a process for
producing silicone IOLs with blue light absorption properties, it
will be manifest to those skilled in the art that various
modifications may be made without departing from the spirit and
scope of the underlying inventive concept and that the same is not
limited to particular processes and structures herein shown and
described except insofar as indicated by the scope of the appended
claims.
* * * * *