U.S. patent application number 10/005560 was filed with the patent office on 2002-08-29 for surface treatment of silicone medical devices with reactive hydrophilic polymers.
Invention is credited to McGee, Joseph A., Ozark, Richard M., Salamone, Joseph C., Valint, Paul L. JR..
Application Number | 20020120084 10/005560 |
Document ID | / |
Family ID | 23225286 |
Filed Date | 2002-08-29 |
United States Patent
Application |
20020120084 |
Kind Code |
A1 |
Valint, Paul L. JR. ; et
al. |
August 29, 2002 |
Surface treatment of silicone medical devices with reactive
hydrophilic polymers
Abstract
The present invention is directed toward the surface treatment
of silicone medical devices such as contact lenses and medical
implants. In particular, the present invention is directed to a
method of modifying the surface of a medical device to increase its
biocompatibility or hydrophilicity by coating the device with a
hydrophilic polymer by means of reaction between reactive
functionalities on the hydrophilic polymer which functionalities
are complementary to reactive functionalities on or near the
surface of the medical device. The present invention is also
directed to a contact lens or other medical device having such a
surface coating.
Inventors: |
Valint, Paul L. JR.;
(Pittsford, NY) ; McGee, Joseph A.; (DeWitt,
NY) ; Salamone, Joseph C.; (Boca Raton, FL) ;
Ozark, Richard M.; (Solvay, NY) |
Correspondence
Address: |
Bausch & Lomb Incorporated
One Bausch & Lomb Place
Rochester
NY
14604
US
|
Family ID: |
23225286 |
Appl. No.: |
10/005560 |
Filed: |
November 8, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10005560 |
Nov 8, 2001 |
|
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09315620 |
May 20, 1999 |
|
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Current U.S.
Class: |
526/260 |
Current CPC
Class: |
G02B 1/043 20130101;
C08J 7/056 20200101; A61L 27/34 20130101; C08J 7/0427 20200101;
Y10T 428/31663 20150401; C08J 2383/04 20130101; G02B 1/043
20130101; C08L 83/10 20130101 |
Class at
Publication: |
526/260 |
International
Class: |
C08F 026/06 |
Claims
1. A method for treating the surface of a silicone medical device
comprising: (a) forming a medical device from a silicone material,
wherein the silicone material comprises monomeric units having
reactive functionalities selected from the group consisting of
azlactone, carboxylic acid, amine, hydroxy and epoxy
functionalities, and combinations thereof; and (b) forming a
hydrophilic reactive polymer having complementary reactive
functionalities along the polymer chain selected from the group
comprising azlactone, isocyanate, acid anhydride, epoxy, hydroxy,
primary or secondary amine, or carboxylic acid functionalities, and
combinations thereof, wherein in the case of the hydroxy or amine
complementary reactive functionalities, the silicone material
comprises azlactone reactive functionalities and in the case of the
carboxylic acid complementary functionality, the silicone material
comprises epoxy reactive functionalities; (c) reacting the
hydrophilic reactive polymer of (b) having complementary reactive
functionalities along the polymer chain with said reactive
functionalities on or near the surface of the medical device of
(a), thus forming a biocompatible surface on the medical
device.
2. The method of claim 1, wherein the medical device is a silicone
contact lens or intraocular lens and the coating is uncolored.
3. The method of claim 1, wherein the medical device is a silicone
hydrogel, continuous-wear contact lens.
4. The method of claim 1, wherein the hydrophilic reactive polymer
comprises 1 to 100 mole percent of monomeric units having said
reactive functionalities.
5. The method of claim 1, wherein the hydrophilic reactive polymer
comprises 0 to 99 mole percent of monomeric units that are derived
from non-reactive hydrophilic monomers.
6. The method of claim 1, wherein the polymer comprises 50 to 95
mole percent of monomeric units derived from non-reactive
hydrophilic monomers selected from the group consisting of
acrylamides, lactones, poly(alkyleneoxy)methacrylates, methacrylic
acid or hydroxyalkyl methacrylates and 5 to 50 percent of monomeric
units derived from functionally reactive monomers selected from the
group consisting of epoxy, azlactone, and anhydride containing
monomers, wherein the alkyl or alkylene groups have 1 to 6 carbon
atoms.
7. The method of claim 7, wherein the functionally reactive
monomers are selected from the group consisting of glycidyl
methacrylate, maleic anhydride, itaconic anhydride, and
isocyanomethacrylate.
8. The method of claim 1, wherein the hydrophilic monomers are
selected from the group consisting of dimethylacrylamide,
acrylamide, and N-vinyl pyrrolidinone.
9. The method of claim 1, wherein the hydrophilic reactive polymer
comprises 0 to 35 mole percent monomeric units derived from
hydrophobic monomers.
10. The method of claim 1, wherein the hydrophilic polymer
comprises oxazolinone moieties having the following formula:
26wherein R.sup.3 and R.sup.4 independently can be an alkyl group
having 1 to 14 carbon atoms; a cycloalkyl group having 3 to 14
carbon atoms; an aryl group having 5 to 12 ring atoms; an arenyl
group having 6 to 26 carbon atoms; and 0 to 3 heteroatoms selected
from S, N, and nonperoxidic 0; or R.sup.3 and R.sup.4 taken
together with the carbon to which they are joined can form a
carbocyclic ring containing 4 to 12 ring atoms, and n is an integer
0 or 1.
11. The method of claim 10, wherein the polymer comprises the
reaction product of a mixture of monomers comprising the monomer
represented by the general formula: 27where R.sup.1 and R.sup.2
independently denote a hydrogen atom or a lower alkyl radical with
one to six carbon atoms, and R.sup.3 and R.sup.4 independently
denote alkyl radicals with one to six carbon atoms or a cycloalkyl
radicals with 5 or 6 carbon atoms.
12. The method of claim 11, wherein the monomer is selected from
the group consisting of 2-vinyl-4,4-dimethyl-2-oxazolin-5-one;
2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one;
2-isopropenyl-4,4-dimethyl-2- -oxazolin-5-one; and
2-vinyl-4,4-dimethyl-2-oxazol in-5-one.
13. The method of claim 10, wherein the medical device is dipped in
a solution comprising at least one hydrophilic reactive polymer in
the absence of a coloring substance.
14. A silicone medical device including a hydrophilic surface
comprising: a medical device made from a silicone material, wherein
the silicone material comprises monomeric units having reactive
functionalities selected from the group consisting of azlactone,
carboxylic acid, amine, hydroxy, and epoxy functionalities, and
compatible combinations thereof; and hydrophilic polymers attached
to the medical device wherein the points of attachment are the
result of the reaction of isocyanate, hydroxy, amine, carboxylic
acid, or ring-opening complementary reactive functionalities or
compatible combinations thereof in monomeric units along the
hydrophilic reactive polymers with said functionalities on or near
the surface of the medical device or the results, wherein in the in
the case of the hydroxy or amine complementary reactive
functionalities, the silicone material comprises azlactone reactive
functionalities and in the case of the carboxylic acid
complementary functionality, the silicone material comprises epoxy
reactive functionalities, thereby producing a clear, transparent
biocompativle coating.
15. The medical device of claim 14, wherein the medical device is a
silicone contact lens or intraocular device.
16. The medical device of claim 14, wherein the medical device is a
silicone hydrogel continuous-wear lens.
17. The medical device of claim 14, wherein the hydrophilic
polymers comprise 1 to 100 mole percent of monomeric units having
said reactive functionalities and 0 to 99 mole percent of monomeric
units that are derived from non-reactive hydrophilic monomers.
18. The medical device of claim 14, wherein the reactive
functionalities are derived from monomers containing one or more of
the following groups: glycidyl, azlactone, isocyanate, and acid
anhydride.
19. The medical device of claim 14, wherein the hydrophilic
monomeric units are derived from monomers selected from the group
consisting of acrylamides, lactams, poly(alkyleneoxy)methacrylates,
methacrylic acid or hydroxyalkyl methacrylates.
20. The medical device of claim 14, wherein the hydrophilic polymer
comprises moieties along the chain having the following formula:
28wherein R.sup.3 and R.sup.4 independently can be an alkyl group
having 1 to 14 carbon atoms; a cycloalkyl group having 3 to 14
carbon atoms; an aryl group having 5 to 12 ring atoms; an arenyl
group having 6 to 26 carbon atoms; and 0 to 3 heteroatoms selected
from S, N, and nonperoxidic 0; or R.sup.1 and R.sup.2 taken
together with the carbon to which they are joined can form a
carbocyclic ring containing 4 to 12 ring atoms, and n is an integer
0 or 1.
21. The medical device claim 14, wherein the hydrophilic polymer
comprises moieties along the chain represented by the general
formula: 29where R.sup.3 and R.sup.4 independently denote a
hydrogen atom or a lower alkyl radical with one to six carbon
atoms, and R.sup.3 and R.sup.4 independently denote alkyl radicals
with one to six carbon atoms or a cycloalkyl radicals with 5 or 6
carbon atoms.
22. The medical device claim 14, wherein hydrophilic polymer chains
attached to the carbonaceous layer are the result of the reaction
of a mixture of polymers comprising (a) a first hydrophilic
reactive polymer having reactive functionalities in monomeric units
along the hydrophilic polymers complementary to reactive
functionalities on the surface of the medical device and, in
addition, (b) a second hydrophilic reactive polymer having
supplemental reactive functionalities that are reactive with the
first hydrophilic reactive polymer.
23. The medical device of claim 22, wherein the first hydrophilic
reactive polymer is an epoxy-functional polymer and the second
hydrophilic reactive polymer is an acid-functional polymer, either
simultaneously or sequentially applied to the substrate to be
coated.
24. The medical device of claim 14, wherein the substrate comprises
a coating comprising the reaction product of a separate
epoxy-functional hydrophilic reactive polymer and an
acid-functional hydrophilic polymer.
25. The medical device of claim 14, wherein the substrate comprises
azlactone-functional monomeric units that have been coverted to
acid groups near or on the surface.
26. A copolymer comprising 1 to 99 mole percent of a monomeric unit
derived from monomers selected from the group consisting of
acrylamides, lactams and poly(alklylene oxides), hydroxyalkyl
methacrylates, wherein the alkylene or alkyl groups have 1 to 6
carbon atoms, and 1 to 99 mole percent of a monomer selected from
the group consisting of the formula: 30where R.sup.1 and R.sup.2
independently denote a hydrogen atom or a lower alkyl radical with
one to six carbon atoms, and R.sup.3 and R.sup.4 independently
denote alkyl radicals with one to six carbon atoms or a cycloalkyl
radicals with 5 or 6 carbon atoms.
27. A method for treating the surface of a silicone medical device
comprising: (a) forming a medical device from a silicone material,
wherein the silicone material comprises monomeric units having
reactive functionalities selected from the group consisting of
azlactone, carboxylic acid, amine, hydroxy and epoxy
functionalities, and combinations thereof and; (b) forming a
hydrophilic reactive polymer having complementary reactive
functionalities along the polymer chain which functionalities are
selected from the group comprising azlactone, isocyanate, acid
anhydride, epoxy, amine, carboxylic acid, and acid functionalities
or compatible combinations thereof, which hydrophilic reactive
polymer comprises 5 to 50 percent of monomeric units derived from
functionally reactive monomers selected from the group consisting
of isocyanate, epoxy, azlactone, anhydride containing monomers, and
combinations thereof, and 0.5 to 20 percent of monomeric units
derived from hydrophobic monomers, wherein in the case of the
hydroxy or amine complementary reactive functionalities, the
silicone material comprises azlactone reactive functionalities and
in the case of the carboxylic acid complementary functionality, the
silicone material comprises epoxy reactive functionalities; (c)
reacting the hydrophilic reactive polymer of (b) having
complementary reactive functionalities along the polymer chain with
said reactive functionalities on or near the surface of the medical
device of (a) in the absence of a coloring substance, thus forming
a biocompatible surface on the medical device.
28. The method of claim 26, wherein the hydrophilic reactive
polymer further comprises 50 to 95 mole percent of monomeric units
derived from non-reactive hydrophilic monomers selected from the
group consisting of acrylamides, lactones,
poly(alkyleneoxy)methacrylates, methacrylic acid or hydroxyalkyl
methacrylates,
Description
FIELD OF THE INVENTION
[0001] The present invention is directed toward the surface
treatment of medical devices such as contact lenses and medical
implants. In particular, the present invention is directed to a
method of modifying the surface of a medical device to increase its
biocompatibility or hydrophilicity by coating the device with a
hydrophilic polymer by reaction between reactive functionalities in
the contact lens material and complementary reactive
functionalities on the hydrophilic polymer. The present invention
is also directed to a contact lens or other medical device having
such a surface coating.
BACKGROUND
[0002] Contact lenses made from silicone-containing materials have
been investigated for a number of years. Such materials can
generally be subdivided into two major classes: hydrogels and
non-hydrogels. Non-hydrogels do not absorb appreciable amounts of
water, whereas hydrogels can absorb and retain water in an
equilibrium state. Hydrogels generally have a water content greater
than about five weight percent and more commonly between about 10
to about 80 weight percent. Regardless of their water content, both
non-hydrogel and hydrogel silicone contact lenses tend to have
relatively hydrophobic, non-wettable surfaces.
[0003] Surface structure and composition determine many of the
physical properties and ultimate uses of solid materials.
Characteristics such as wetting, friction, and adhesion or
lubricity are largely influenced by surface characteristics. The
alteration of surface characteristics is of special significance in
biotechnical applications, where biocompatibility is of particular
concern. Therefore, those skilled in the art have long recognized
the need for rendering the surface of contact lenses and other
medical devices hydrophilic or more hydrophilic. Increasing the
hydrophilicity of the contact-lens surface improves the wettability
of the contact lenses with tear fluid in the eye. This in turn
improves the wear comfort of the contact lenses. In the case of
continuous-wear lenses, the surface is especially important. The
surface of a continuous-wear lens must be designed not only for
comfort, but to avoid adverse reactions such as corneal edema,
inflammation, or lymphocyte infiltration. Improved methods have
accordingly been sought for modifying the surfaces of contact
lenses, particularly high-Dk (highly oxygen permeable) lenses
designed for continuous (overnight) wear.
[0004] Various patents disclose the attachment of hydrophilic or
otherwise biocompatible polymeric chains to the surface of a
contact lens in order to render the lens more biocompatible. For
example, U.S. Pat. No. 5,652,014 teaches amination of a substrate
followed by reaction with other polymers, such as a PEO star
molecule or a sulfated polysaccharide. One problem with such an
approach is that the polymer chain density is limited due to the
difficult of attaching the polymer to the silicone substrate.
[0005] U.S. Pat. No. 5,344,701 discloses the attachment of
oxazolinone or azlactone monomers to a substrate by means of
plasma. The invention has utility in the field of surface-mediated
or catalyzed reactions for synthesis or site-specific separations,
including affinity separation of biomolecules, diagnostic supports
and enzyme membrane reactors. The oxazolinone group is attached to
a porous substrate apparently by reaction of the ethylenic
unsaturation in the oxazolinone monomer with radicals formed by
plasma on the substrate surface. Alternatively, the substrate can
be coated with monomers and reacted with plasma to form a
cross-linked coating. The oxazolinone groups that have been
attached to the surface can then be used to attach a biologically
active material, for example, proteins, since the oxazolinone is
attacked by amines, thiols, and alcohols. U.S. Pat. No. 5,364,918
to Valint et al. and U.S. Pat. No. 5,352,714 to Lai et al. disclose
the use of oxazolinone monomers as internal wetting agents for
contact lenses, which agents may migrate to the surface of the
contact lens.
[0006] U.S. Pat. No. 4,734,475 to Goldenberg et al. discloses the
use of a contact lens fabricated from a polymer comprising oxirane
(epoxy) substituted monomeric units in the backbone, such that the
outer surfaces of the lens contain a hydrophilic inducing amount of
the reaction product of the oxirane monomeric units with a water
soluble reactive organic, amine, alcohol, thiol, urea, thiourea,
sulfite, bisulfite or thiosulfate.
[0007] In view of the above, it would be desirable to find an
optically clear, hydrophilic coating for the surface of a silicone
medical device that renders the device more biocompatible. Still
further, it would be desirable to form a coating for a silicone
hydrogel contact lens that is more comfortable for a longer period
of time, simultaneously tear-wettable and highly permeable to
oxygen. It would be desirable if such a biocompatibilized lens was
capable of continuous wear overnight, preferably for a week or more
without adverse effects to the cornea.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 shows an Atomic Force Microscopy (AFM) topographical
images (50 .mu.m.sup.2) of a control contact lens described in
Example 15 below, for comparison to a contact lenses according to
the invention; the image of the anterior side of the lens is shown
on the left of FIG. 1 and the image of the posterior side is shown
on the right.
[0009] FIG. 2 shows an Atomic Force Microscopy (AFM) topographical
images (50 .mu.m.sup.2) of a contact lens coated described in
Example 14 according to one embodiment of the present invention,
which lens is a silicone rigid-gas-permeable lens coated with a
polymer as described in Example 10, a copolymer of dimethyl
acrylamide and glycidyl methacrylate.
[0010] FIG. 3 shows an Atomic Force Microscopy (AFM) topographical
images (50 .mu.m.sup.2) of a contact lens coated described in
Example 15 according to one embodiment of the present invention,
which lens is a silicone rigid-gas-permeable lens coated with a
combination of the hydrophilic copolymers described in Examples 10
and Example 12.
[0011] FIG. 4 shows Atomic Force Microscopy (AFM) topographical
images (50 .mu.m.sup.2) of a control contact lens described in
Example 16 for comparison to other lenses according to another
embodiment of the present invention, which lens is a silicone
hydrogel lens coated with a polymer as described in Example 11.
[0012] FIG. 5 shows Atomic Force Microscopy (AFM) topographical
images (50 .mu.m.sup.2) of a contact lens coated described in
Example 16 according to one embodiment of the present invention,
which lens is a silicone hydrogel lens coated with a polymer as
described in Example 11, a copolymer of dimethyl acrylamide,
glycidyl methacrylate, and octafluoropentylmethacrylate.
[0013] FIG. 6 shows Atomic Force Microscopy (AFM) topographical
images (50 .mu.m.sup.2) of a contact lens coated described in
Example 16 according to one embodiment of the present invention,
which lens is a silicone hydrogel lens coated with a polymer as
described in Example 11, a copolymer of dimethyl acrylamide,
glycidyl methacrylate, and octafluoropentylmethacrylate, which is
used for coating at a higher concentration than was used for
coating the lens in FIG. 5.
SUMMARY OF THE INVENTION
[0014] The present invention is directed toward surface treatment
of silicone contact lenses and other silicone medical devices,
including a method of modifying the surface of a contact lens to
increase its hydrophilicity or wettability. The surface treatment
comprises the attachment of hydrophilic polymer chains to the
surface of the contact lens substrate, by means of reactive
functionalities in the lens substrate material reacting with
complementary reactive functionalities in monomeric units along a
hydrophilic reactive polymer. The present invention is also
directed to a medical device, including contact lenses, intraocular
lenses, catheters, implants, and the like, comprising a surface
made by such a method.
DETAILED DESCRIPTION OF THE INVENTION
[0015] As stated above, the present invention is directed toward
surface treatment of silicone medical devices, including contact
lenses, intraocular lenses and vascular implants, to improve their
biocompatibility. By the term silicone, it is meant that the
material being treated is an organic polymer comprising at least
five percent by weight silicone (--OSi-- linkages), preferably 10
to 100 percent by weight silicone, more preferably 30 to 90 percent
by weight silicone. The present invention is especially
advantageous for application to contact lenses, either silicone
hydrogels or silicone rigid-gas-permeable materials. The invention
is especially advantageous for silicone hydrogel continuous-wear
lenses. Hydrogels are a well-known class of materials, which
comprise hydrated, cross-linked polymeric systems containing water
in an equilibrium state. Silicone -hydrogels generally have a water
content greater than about five weight percent and more commonly
between about ten to about eighty weight percent. Such materials
are usually prepared by polymerizing a mixture containing at least
one silicone-containing monomer and at least one hydrophilic
monomer. Either the silicone-containing monomer or the hydrophilic
monomer may function as a cross-linking agent (a cross-linker being
defined as a monomer having multiple polymerizable functionalities)
or a separate cross-linker may be employed. Applicable
silicone-containing monomeric units for use in the formation of
silicone hydrogels are well known in the art and numerous examples
are provided in U.S. Pat. Nos. 4,136,250; 4,153,641; 4,740,533;
5,034,461; 5,070,215; 5,260,000; 5,310,779; and 5,358,995.
[0016] Examples of applicable silicon-containing monomeric units
include bulky polysiloxanylalkyl (meth)acrylic monomers. An example
of bulky polysiloxanylalkyl (meth)acrylic monomers is represented
by the following Formula I: 1
[0017] wherein:
[0018] X denotes --O-- or --NR--;
[0019] each R.sub.18 independently denotes hydrogen or methyl;
[0020] each R.sub.19 independently denotes a lower alkyl radical,
phenyl radical or a group represented by 2
[0021] wherein each R.sub.19' independently denotes a lower alkyl
or phenyl radical; and
[0022] h is 1 to 10.
[0023] Some preferred bulky monomers are methacryloxypropyl
tris(trimethyl-siloxy)silane or tris(trimethylsiloxy)silylpropyl
methacrylate, sometimes referred to as TRIS and
tris(trimethylsiloxy)sily- lpropyl vinyl carbamate, sometimes
referred to as TRIS-VC.
[0024] Such bulky monomers may be copolymerized with a silicone
macromonomer, which is a poly(organosiloxane) capped with an
unsaturated group at two or more ends of the molecule. U.S. Pat.
No. 4,153,641 to Deichert et al. discloses, for example, various
unsaturated groups, including acryloxy or methacryloxy.
[0025] Another class of representative silicone-containing monomers
includes silicone-containing vinyl carbonate or vinyl carbamate
monomers such as:
1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane;
3-(trimethylsilyl)propyl vinyl carbonate;
3-(vinyloxycarbonylthio)propyl-- [tris(trimethylsiloxy)silane];
3-[tris(tri-methylsiloxy)silyl]propyl vinyl carbamate;
3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;
3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;
t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl
vinyl carbonate; and trimethylsilylmethyl vinyl carbonate.
[0026] Another class of silicon-containing monomers includes
polyurethane-polysiloxane macromonomers (also sometimes referred to
as prepolymers), which may have hard-soft-hard blocks like
traditional urethane elastomers. Examples of silicone urethanes are
disclosed in a variety or publications, including Lai, Yu-Chin,
"The Role of Bulky Polysiloxanylalkyl Methacryates in
Polyurethane-Polysiloxane Hydrogels," Journal of Applied Polymer
Science, Vol. 60, 1193-1199 (1996). PCT Published Application No.
WO 96/31792 and U.S. Pat. Nos. 5,451,617 and 5,451,651 disclose
examples of such monomers, which disclosure is hereby incorporated
by reference in its entirety. Further examples of silicone urethane
monomers are represented by Formulae II and III:
E(*D*A*D*G).sub.a*D*A*D*E'; (II)
[0027] or
E(*D*G*D*A).sub.a*D*G*D*E'; (III)
[0028] wherein:
[0029] D denotes an alkyl diradical, an alkyl cycloalkyl diradical,
a cycloalkyl diradical, an aryl diradical or an alkylaryl diradical
having 6 to 30 carbon atoms;
[0030] G denotes an alkyl diradical, a cycloalkyl diradical, an
alkyl cycloalkyl diradical, an aryl diradical or an alkylaryl
diradical having 1 to 40 carbon atoms and which may contain ether,
thio or amine linkages in the main chain;
[0031] * denotes a urethane or ureido linkage;
[0032] a is at least 1;
[0033] A denotes a divalent polymeric radical of Formula IV: 3
[0034] wherein:
[0035] each Rs independently denotes an alkyl or fluoro-substituted
alkyl group having 1 to 10 carbon atoms which may contain ether
linkages between carbon atoms;
[0036] m' is at least 1; and
[0037] p is a number that provides a moiety weight of 400 to
10,000;
[0038] each of E and E' independently denotes a polymerizable
unsaturated organic radical represented by Formula VI: 4
[0039] wherein:
[0040] R.sub.23 is hydrogen or methyl;
[0041] R.sub.24 is hydrogen, an alkyl radical having 1 to 6 carbon
atoms, or a --CO--Y--R.sub.26 radical wherein Y is --O--, --S-- or
--NH--;
[0042] R.sub.25 is a divalent alkylene radical having 1 to 10
carbon atoms;
[0043] R.sub.26 is a alkyl radical having 1 to 12 carbon atoms;
[0044] X denotes --CO-- or --OCO--;
[0045] Z denotes --O-- or --NH--;
[0046] Ar denotes an aromatic radical having 6 to 30 carbon
atoms;
[0047] w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.
[0048] A preferred silicone-containing urethane monomer is
represented by Formula (VII): 5
[0049] wherein m is at least 1 and is preferably 3 or 4, a is at
least 1 and preferably is 1, p is a number which provides a moiety
weight of 400 to 10,000 and is preferably at least 30, R.sub.27 is
a diradical of a diisocyanate after removal of the isocyanate
group, such as the diradical of isophorone diisocyanate, and each
E" is a group represented by: 6
[0050] Another class of representative silicone-containing monomers
includes fluorinated monomers. Such monomers have been used in the
formation of fluorosilicone hydrogels to reduce the accumulation of
deposits on contact lenses made therefrom, as described in U.S.
Pat. Nos. 4,954,587, 5,079,319 and 5,010,141. The use of
silicone-containing monomers having certain fluorinated side
groups, i.e. --(CF.sub.2)--H, have been found to improve
compatibility between the hydrophilic and silicone-containing
monomeric units, as described in U.S. Pat. Nos. 5,387,662 and
5,321,108.
[0051] In one preferred embodiment of the invention, a silicone
hydrogel material comprises (in bulk, that is, in the monomer
mixture that is copolymerized) 5 to 50 percent, preferably 10 to
25, by weight of one or more silicone macromonomers, 5 to 75
percent, preferably 30 to 60 percent, by weight of one or more
polysiloxanylalkyl (meth)acrylic monomers, and 10 to 50 percent,
preferably 20 to 40 percent, by weight of a hydrophilic monomer.
Examples of hydrophilic monomers include, but are not limited to,
ethylenically unsaturated lactam-containing monomers such as
N-vinyl pyrrolidinone, methacrylic and acrylic acids; acrylic
substituted alcohols, such as 2-hydroxyethylmethacrylate and
2-hydroxyethylacrylate and acrylamides, such as methacrylamide and
N,N-dimethylacrylamide, vinyl carbonate or vinyl carbamate monomers
such as disclosed in U.S. Pat. Nos. 5,070,215, and oxazolinone
monomers such as disclosed in U.S. Pat. No. 4,910,277. Other
hydrophilic monomers will be apparent to one skilled in the
art.
[0052] The above silicone materials are merely exemplary, and other
materials for use as substrates that can benefit by being coated
according to the present invention have been disclosed in various
publications and are being continuously developed for use in
contact lenses and other medical devices.
[0053] As indicated above, the present invention is directed to the
modification of the surface of a silicone medical device such as a
contact lens by means of attaching to the surface hydrophilic
polymer chains. The hydrophilic polymer chains are attached to the
surface by means of exposing the surface to hydrophilic reactive
polymers (inclusive of oligomers) having ring-opening or isocyanate
reactive functionalities complementary to reactive groups on the
surface of the medical device. Alternatively, the hydrophilic
polymer chains may be attached to the surface by means of exposing
the surface to hydrophilic reactive polymers (inclusive of
oligomers) having hydroxy or (primary or secondary) amine groups
complementary to azlactone reactive groups in the silicone material
or having carboxylic acid complementary groups complementary to
epoxy reactive groups in the silicone material. In other words,
chemical functionality at the surface of the medical device is
utilized to covalently attach hydrophilic polymers to the object or
substrate.
[0054] The hydrophilic reactive polymers may be homopolymers or
copolymers comprising reactive monomeric units that contain either
an isocyanate or a ring-opening reactive functionality optionally.
Although these reactive monomeric units may also be hydrophilic,
the hydrophilic reactive polymer may also be a copolymer of
reactive monomeric units copolymerized with one or more of various
non-reactive hydrophilic monomeric units. Lesser amounts of
hydrophobic monomeric units may optionally be present in the
hydrophilic polymer. The ring-opening monomers include
azlactone-functional, epoxy-functional and
acid-anhydride-functional monomers.
[0055] Mixtures of hydrophilic reactive polymers may be employed.
For example, the hydrophilic polymer chains attached to the
substrate may be the result of the reaction of a mixture of
polymers comprising (a) a first hydrophilic reactive polymer having
reactive functionalities in monomeric units along the hydrophilic
polymers complementary to reactive functionalities on the substrate
surface and, in addition, (b) a second hydrophilic reactive polymer
having supplemental reactive functionalities that are reactive with
the first hydrophilic reactive polymer. A mixture comprising an
epoxy-functional polymer with an acid-functional polymer, either
simultaneously or sequentially applied to the substrate to be
coated, have been found to provide relatively thick coatings.
[0056] Preferably the hydrophilic reactive polymers comprise 1 to
100 mole percent of reactive monomeric units, more preferably 5 to
50 mole percent, most preferably 10 to 40 mole percent. The
polymers may comprise 0 to 99 mole percent of non-reactive
hydrophilic monomeric units, preferably 50 to 95 mole percent, more
preferably 60 to 90 mole percent (the reactive monomers, once
reacted may also be hydrophilic, but are by definition mutually
exclusive with the monomers referred to as hydrophilic monomers
which are non-reactive). The weight average molecular weight of the
hydrophilic reactive polymer may suitably range from about 200 to
1,000,000, preferably from about 1,000 to 500,000, most preferably
from about 5,000 to 100,000.
[0057] Hydrophilic monomers may be aprotic types such as
acrylamides (N,N-dimethylacrylamide, DMA), lactams such as
N-vinylpyrrolidinone, and poly(alklylene oxides) such as
methoxypolyoxyethylene methacrylates or may be protic types such as
methacrylic acid or hydroxyalkyl methacrylates such as hydroxyethyl
methacrylate. Hydrophilic monomers may also include zwitterions
such as N,N-dimethyl-N-methacryloxyethyl-N-(3-su-
lfopropyl)-ammonium betain (SPE) and
N,N-dimethyl-N-methacrylamidopropyl-N- -(3-sulfopropyl)-ammonium
betain (SPP).
[0058] Monomeric units which are hydrophobic optionally may be used
in amounts up to 35 mole percent, preferably 0 to 20 mole percent,
most preferably 0 to 10 mole percent. Examples of hydrophobic
monomers are alkyl methacrylate, fluorinated alkyl methacrylates,
long-chain acrylamides such as octyl acrylamide, and the like.
[0059] As mentioned above, the hydrophilic reactive polymer may
comprise reactive monomeric units derived from
azlactone-functional, epoxy-functional and
acid-anhydride-functional monomers. For example, an
epoxy-functional hydrophilic reactive polymer for coating a lens
can be a copolymer containing glycidyl methacrylate (GMA) monomeric
units, which will react, for example, with a lens substrate
comprising carboxylic acid groups. Preferred examples of
anhydride-functional hydrophilic reactive polymers comprise
monomeric units derived from monomers such as maleic anhydride and
itaconic anhydride.
[0060] In general, epoxy-functional reactive groups or
anhydride-functional reactive groups in the hydrophilic reactive
polymer react with carboxylic (--COOH), alcohol (--OH), or primary
amine (--NH.sub.2) groups in the substrate, for example, substrates
made from polymers comprising as monomeric units from methacrylic
acid (MAA), hydroxyalkylmethacrylates such as
hydroxyethylmethacrylate (HEMA), or aminoalkyl methacrylates such
as aminopropylmethacrylate, all common and commercially available
monomers. In the case of alcohols, a catalyst such as
4-dimethylaminopyridine may be used to speed the reaction at room
temperature, as will be understood by the skilled chemist. Acidic
groups may also be created in the substrate by the use of azlactone
monomeric units that are hydrolyzed to the acid. These acid groups
can be reacted with an epoxy or anhydride group in the hydrophilic
reactive polymer. See, for example, U.S. Pat. No. 5,364,918 to
Valint and McGee, herein incorporated by reference in its entirety,
for examples of such substrates.
[0061] In general, azlactone or isocyanate-functional groups in the
hydrophilic reactive polymers may similarly react with amines or
alcohols in the polymer substrate, reactions involving an alcohol
preferably in the presence of a catalyst. In addition, carboxylic
acids, amines and hydrolyzed azlactones in the hydrophilic reactive
polymers may react with epoxy-groups in the substrate, for example,
the monomeric units described in U.S. Pat. No. 4,734,475 to
Goldenberg et al., herein incorporated by reference in its
entirety.
[0062] In a preferred embodiment of the invention, preformed
(non-polymerizable) hydrophilic polymers containing repeat units
derived from at least one ring-opening monomer, an
isocyanate-containing monomer, an amine-containing monomer, a
hydroxy-containing monomer, or a carboxylic containing monomer are
reacted with reactive groups on the surface of the medical device
such as a contact lens substrate. Typically, the hydrophilic
reactive polymers are attached to the substrate at one or more
places along the chain of the polymer. After attachment, any
unreacted reactive functionalities in the hydrophilic reactive
polymer may be hydrolyzed to a non-reactive moiety, in the case of
epoxy, isocyanate or ring-opening monomeric units.
[0063] Suitable hydrophilic non-reactive monomers for comprising
the hydrophilic reactive polymers include generally water soluble
conventional vinyl monomers such as 2-hydroxyethyl-; 2- and
3-hydroxypropyl-; 2,3-dihydroxypropyl-; polyethoxyethyl-; and
polyethoxypropylacrylates, methacrylates, acrylamides and
methacrylamides; acrylamide, methacrylamide, N-methylacrylamide,
N-methylmethacrylamide, N,N-dimethylacrylamide,
N,N-dimethylmethacrylamid- e, N,N-dimethyl- and
N,N-diethyl-aminoethyl acrylate and methacrylate and the
corresponding acrylamides and methacrylamides; 2- and
4-vinylpyridine; 4- and 2-methyl-5-vinylpyridine;
N-methyl-4-vinylpiperid- ine; 2-methyl-1-vinylimidazole;
N,-N-dimethylallylamine; dimethylaminoethyl vinyl ether and
N-vinylpyrrolidone.
[0064] Included among the useful non-reactive monomers are
generally water soluble conventional vinyl monomers such as
acrylates and methacrylates of the general structure 7
[0065] where
[0066] R.sub.2 is hydrogen or methyl and R.sub.3 is hydrogen or is
an aliphatic hydrocarbon group of up to 10 carbon atoms substituted
by one or more water solubilizing groups such as carboxy, hydroxy,
amino, lower alkylamino, lower dialkyamino, a polyethylene oxide
group with from 2 to about 100 repeating units, or substituted by
one or more sulfate, phosphate sulfonate, phosphonate, carboxamido,
sulfonamido or phosphonamido groups, or mixtures thereof;
[0067] Preferably R.sub.3 is an oligomer or polymer such as
polyethylene glycol, polypropylene glycol, poly(ethylene-propylene)
glycol, poly(hydroxyethyl methacrylate), poly(dimethyl acrylamide),
poly(acrylic acid), poly(methacrylic acid), polysulfone, poly(vinyl
alcohol), polyacrylamide, poly(acrylamide-acrylic acid)
poly(styrene sulfonate) sodium salt, poly(ethylene oxide),
poly(ethylene oxide-propylene oxide), poly(glycolic acid),
poly(lactic acid), poly(vinylpyrrolidone), cellulosics,
polysaccharides, mixtures thereof, and copolymers thereof;
[0068] acrylamides and methacrylamides of the formula 8
[0069] where R.sub.2 and R.sub.3 are as defined above;
[0070] acrylamides and methacrylamides of the formula 9
[0071] where R.sub.4 is lower alkyl of 1 to 3 carbon atoms and
R.sub.2 is as defined above;
[0072] maleates and fumarates of the formula:
R.sub.3OOCH.dbd.CHCOOR.sub.3
[0073] wherein R.sub.3 is as defined above;
[0074] vinyl ethers of the formula
H.sub.2C.dbd.CH--O--R.sub.3
[0075] where R.sub.3 is as defined above;
[0076] aliphatic vinyl compounds of the formula
R.sub.2CH.dbd.CHR.sub.3
[0077] where R.sub.2 is as defined above and R.sub.3 is as defined
above with the proviso that R.sub.3 is other than hydrogen; and
[0078] vinyl substituted heterocycles, such as vinyl pyridines,
piperidines and imidazoles and N-vinyl lactams, such as
N-vinyl-2-pyrrolidone.
[0079] Included among the useful water soluble monomers are acrylic
and methacrylic acid; itaconic, crotonic, fumaric and maleic acids
and the lower hydroxyalkyl mono and diesters thereof, such as the
2-hydroxethyl fumarate and maleate, sodium acrylate and
methacrylate; 2-methacryloyloxyethylsulfonic acid and allylsulfonic
acid.
[0080] The inclusion of some hydrophobic monomers in the
hydrophilic reactive polymers may provide the benefit of causing
the formation of tiny dispersed polymer aggregates in solution,
evidenced by a haziness in the solution of the polymer. Such
aggregates can also be observed in Atomic Force Microscopy images
of the coated medical device.
[0081] Suitable hydrophobic copolymerizable monomers include water
insoluble conventional vinyl monomers such as acrylates and
methacrylates of the general formula 10
[0082] where R.sub.2 is as defined above and R.sub.5 is a straight
chain or branched aliphatic, cycloaliphatic or aromatic group
having up to 20 carbon atoms which is unsubstituted or substituted
by one or more alkoxy, alkanoyloxy or alkyl of up to 12 carbon
atoms, or by halo, especially chloro or preferably fluoro, C2 to C5
polyalkyleneoxy of 2 to about 100 units, or an oligomer such as
polyethylene, poly(methyl methacrylate), poly(ethyl methacrylate),
or poly(glycidyl methacrylate), mixtures thereof, and copolymers
thereof,
[0083] acrylamides and methacylamides of the general formula 11
[0084] where R.sub.2 and R.sub.5 are defined above;
[0085] vinyl ethers of the formula
H.sub.2C.dbd.CH--O--R.sub.5
[0086] where R.sub.5 is as defined above;
[0087] vinyl esters of the formula
H.sub.2C.dbd.CH--OCO--R.sub.5
[0088] where R.sub.5 is as defined above;
[0089] maleates and fumarates of the formula
R.sub.5OOC--HC.dbd.CH--OOOR.sub.5
[0090] where R.sub.5 is as defined above; and
[0091] vinylic substituted hydrocarbons of the formula
R.sub.2CH.dbd.CHR.sub.5
[0092] where R.sub.2 and R.sub.5 is as defined above
[0093] Useful or suitable hydrophobic monomers include, for
example: methyl, ethyl, propyl, isopropyl, butyl, ethoxyethyl,
methoxyethyl, ethoxypropyl, phenyl, benzyl, cyclohexyl,
hexafluoroisopropyl, or n-octyl-acrylates and -methacrylates as
well as the corresponding acrylamides and methacrylamides; dimethyl
fumarate, dimethyl maleate, diethyl fumarate, methyl vinyl ether,
ethoxyethyl vinyl ether, vinyl acetate, vinyl propionate, vinyl
benzoate, acrylonitrile, styrene, alpha-methylstyrene, 1-hexene,
vinyl chloride, vinyl methylketone, vinyl stearate, 2-hexene and
2-ethylhexyl methacrylate.
[0094] The hydrophilic reactive polymers are synthesized in a
manner known per se from the corresponding monomers (the term
monomer here also including a macromer) by a polymerization
reaction customary to the person skilled in the art. Typically, the
hydrophilic reactive polymers or chains are formed by: (1) mixing
the monomers together; (2) adding a polymerization initiator; (3)
subjecting the monomer/initiator mixture to a source of ultraviolet
or actinic radiation and curing said mixture. Typical
polymerization initiators include free-radical-generating
polymerization initiators of the type illustrated by acetyl
peroxide, lauroyl peroxide, decanoyl peroxide, coprylyl peroxide,
benzoyl peroxide, tertiary butyl peroxypivalate, sodium
percarbonate, tertiary butyl peroctoate, and
azobis-isobutyronitrile (AIBN). Ultraviolet free-radical initiators
illustrated by diethoxyacetophenone can also be used. The curing
process will of course depend upon the initiator used and the
physical characteristics of the comonomer mixture such as
viscosity. In any event, the level of initiator employed will vary
within the range of 0.01 to 2 weight percent of the mixture of
monomers. Usually, a mixture of the above-mentioned monomers is
warmed with addition of a free-radical former.
[0095] A polymerization to form the hydrophilic reactive polymer
can be carried out in the presence or absence of a solvent.
Suitable solvents are in principle all solvents which dissolve the
monomer used, for example water; alcohols such as lower alkanols,
for example, ethanol and methanol; carboxamides such as
dimethylformamide, dipolar aprotic solvents such as dimethyl
sulfoxide or methyl ethyl ketone; ketones such as acetone or
cyclohexanone; hydrocarbons such as toluene; ethers such as THF,
dimethoxyethane or dioxane; halogenated hydrocarbons such as
trichloroethane, and also mixtures of suitable solvents, for
example mixtures of water and an alcohol, for example a
water/ethanol or water/methanol mixture.
[0096] In a method according to the present invention, the contact
lens or other medical device may be exposed to hydrophilic reactive
polymers by immersing the substrate in a solution containing the
polymers. For example, a contact lens may be placed or dipped for a
suitable period of time in a solution of the hydrophilic reactive
polymer or copolymer in a suitable medium, for example, an aprotic
solvent such as acetonitrile.
[0097] As indicated above, one embodiment of the invention involves
the attachment of reactive hydrophilic polymers to a medical
device, which polymers comprise isocyanate-containing monomeric
units or ring-opening monomeric units. In one embodiment of the
present invention, the ring-opening reactive monomer has an
azlactone group represented by the following formula: 12
[0098] wherein R.sup.3 and R.sup.4 independently can be an alkyl
group having 1 to 14 carbon atoms, a cycloalkyl group having 3 to
14 carbon atoms, an aryl group having 5 to 12 ring atoms, an arenyl
group having 6 to 26 carbon atoms, and 0 to 3 heteroatoms
non-peroxidic selected from S, N, and O, or R.sup.3 and R.sup.4
taken together with the carbon to which they are joined can form a
carbocyclic ring containing 4 to 12 ring atoms, and n is an integer
0 or 1. Such monomeric units are disclosed in U.S. Pat. No.
5,177,165 to Valint et al.
[0099] The ring structure of such reactive functionalities is
susceptible to nucleophilic ring-opening reactions with
complementary reactive functional groups on the surface of the
substrate being treated. For example, the azlactone functionality
can react with primary amines, hydroxyls, or acids in the
substrate, as mentioned above, to form a covalent bond between the
substrate and the hydrophilic reactive polymer at one or more
locations along the polymer. A plurality of attachments can form a
series of polymer loops on the substrate, wherein each loop
comprises a hydrophilic chain attached at both ends to the
substrate.
[0100] Azlactone-functional monomers for making the hydrophilic
reactive polymer can be any monomer, prepolymer, or oligomer
comprising an azlactone functionality of the above formula in
combination with a vinylic group on an unsaturated hydrocarbon to
which the azlactone is attached. Preferably,
azlactone-functionality is provided in the hydrophilic polymer by
2-alkenyl azlactone monomers. The 2-alkenyl azlactone monomers are
known compounds, their synthesis being described, for example, in
U.S. Pat. Nos. 4,304,705; 5,081,197; and 5,091,489 (all Heilmann et
al.) the disclosures of which are incorporated herein by reference.
Suitable 2-alkenyl azlactones include:
[0101] 2-ethenyl-1,3-oxazolin-5-one,
[0102] 2-ethenyl-4-methyl-1,3-oxazolin-5-one,
[0103] 2-isopropenyl-1,3-oxazolin-5-one,
[0104] 2-isopropenyl-4-methyl-1,3-oxazolin-5-one,
[0105] 2-ethenyl-4,4-dimethyl-1,3-oxazolin-5-one,
[0106] 2-isopropenyl-4,-dimethyl-1,3-oxazolin-5-one,
[0107] 2-ethenyl-4-methyl-ethyl-1,3-oxazolin-5-one,
[0108] 2-isopropenyl-4-methyl-4-butyl-1,3-oxazolin-5-one,
[0109] 2-ethenyl-4,4-dibutyl-1,3-oxazolin-5-one,
[0110] 2-isopropenyl-4-methyl-4-dodecyl-1,3-oxazolin-5-one,
[0111] 2-isopropenyl-4,4-diphenyl-1,3-oxazolin-5-one,
[0112] 2-isopropenyl-4,4-pentamethylene-1,3-oxazolin-5-one,
[0113] 2-isopropenyl-4,4-tetramethylene-1,3-oxazolin-5-one,
[0114] 2-ethenyl-4,4-diethyl-1,3-oxazolin-5-one,
[0115] 2-ethenyl-4-methyl-4-nonyl-1,3-oxazolin-5-one,
[0116] 2-isopropenyl-methyl-4-phenyl-1,3-oxazolin-5-one,
[0117] 2-isopropenyl-4-methyl-4-benzyl-1,3-oxazolin-5-one, and
[0118] 2-ethenyl-4,4-pentamethylene-1,3-oxazolin-5-one,
[0119] More preferably, the azlactone monomers are a compound
represented by the following general formula: 13
[0120] where R.sup.1 and R.sup.2 independently denote a hydrogen
atom or a lower alkyl radical with one to six carbon atoms, and
R.sup.3 and R.sup.4 independently denote alkyl radicals with one to
six carbon atoms or a cycloalkyl radical with five or six carbon
atoms. Specific examples include
2-isopropenyl-4,4-dimethyl-2-oxazolin-5-one (IPDMO),
2-vinyl-4,4-dimethyl-2-oxazolin-5-one (VDMO),
spiro-4'-(2'-isopropenyl-2'- -oxazolin-5-one) cyclohexane (IPCO),
cyclohexane-spiro-4'-(2'-vinyl-2'-oxa- zol-5'-one) (VCO), and
2-(-1-propenyl)-4,4-dimethyl-oxazol-5-one (PDMO) and the like.
[0121] These compounds may be prepared by the general reaction
sequence: 14
[0122] The first step is a Shotten-Bauman acylation of an amino
acid. The polymerizable functionality is introduced by using either
acryloyl or methacryloyl chloride. The second step involves a ring
closure with a chloroformate to yield the desired oxazolinone. The
product is isolated and purified by the usual procedures of organic
chemistry.
[0123] As indicated above, the compounds can be copolymerized with
hydrophilic and/or hydrophobic comonomers to form hydrophilic
reactive polymers. After attachment to the desired substrate, any
unreacted oxazolinone groups may then be hydrolyzed in order to
convert the oxazolinone components into amino acids. In general,
the hydrolysis step will follow the general reaction of: 15
[0124] The carbon-carbon double bond between the R.sup.1 and
R.sup.2 radicals is shown unreacted, but the reaction can take
place when copolymerized into a polymer.
[0125] Non-limiting examples of comonomers useful to be
copolymerized with azlactone functional moieties to form the
hydrophilic reactive polymers used to coat a medical device include
those mentioned above, preferably dimethylacrylamide, N-vinyl
pyrrolidinone. Further examples of comonomers are disclosed in
European Patent Publication 0 392 735, the disclosure of which is
incorporated by reference. Preferably, dimethylacrylamide is used
as a comonomer in order to impart hydrophilicity to the
copolymer.
[0126] Such azlactone-functional monomers can be copolymerized with
other monomers in various combinations of weight percentages. Using
a monomer of similar reactivity ratio to that of an azlactone
monomer will result in a random copolymer. Determination of
reactivity ratios for copolymerization are disclosed in Odian,
Principles of Polymerization, 2nd Ed., John Wiley & Sons, p.
425-430 (1981), the disclosure of which is incorporated by
reference herein. Alternatively, use of a comonomer having a higher
reactivity to that of an azlactone will tend to result in a block
copolymer chain with a higher concentration of
azlactone-functionality near the terminus of the chain.
[0127] Although not as preferred as monomers, azlactone-functional
prepolymers or oligomers having at least one free-radically
polymerizable site can also be utilized for providing
azlactone-functionality in the hydrophilic reactive polymer
according to the present invention. Azlactone-functional oligomers,
for example, are prepared by free radical polymerization of
azlactone monomers, optionally with comonomers as described in U.S.
Pat. Nos. 4,378,411 and 4,695,608, incorporated by reference
herein. Non-limiting examples of azlactone-functional oligomers and
prepolymers are disclosed in U.S. Pat. Nos. 4,485,236 and 5,081,197
and European Patent Publication 0 392 735, all incorporated by
reference herein.
[0128] In another embodiment of the invention, the ring-opening
reactive group in the hydrophilic reactive polymer is an epoxy
functionality. The preferred epoxy-functional monomer is an
oxirane-containing monomer such as glycidyl methacrylate, allyl
glycidyl ether, 4-vinyl-1-cyclohexene-1,2- -epoxide and the like,
although other epoxy-containing monomers may be used.
[0129] The hydrophilic reactive polymers are attached to silicone
medical devices which may be made by conventional manufacturing
processes. For example, contact lenses for application of the
present invention can be manufactured employing various
conventional techniques, to yield a shaped article having the
desired posterior and anterior lens surfaces. Spincasting methods
are disclosed in U.S. Pat. Nos. 3,408,429 and 3,660,545; preferred
static casting methods are disclosed in U.S. Pat. Nos. 4,113,224
and 4,197,266. Curing of the monomeric mixture is often followed by
a machining operation in order to provide a contact lens having a
desired final configuration. As an example, U.S. Pat. No. 4,555,732
discloses a process in which an excess of a monomeric mixture is
cured by spincasting in a mold to form a shaped article having an
anterior lens surface and a relatively large thickness. The
posterior surface of the cured spincast article is subsequently
lathe cut to provide a contact lens having the desired thickness
and posterior lens surface. Further machining operations may follow
the lathe cutting of the lens surface, for example, edge-finishing
operations.
[0130] After producing a lens having the desired final shape, it is
desirable to remove residual solvent from the lens before
edge-finishing operations. This is because, typically, an organic
diluent is included in the initial monomeric mixture in order to
minimize phase separation of polymerized products produced by
polymerization of the monomeric mixture and to lower the glass
transition temperature of the reacting polymeric mixture, which
allows for a more efficient curing process and ultimately results
in a more uniformly polymerized product. Sufficient uniformity of
the initial monomeric mixture and the polymerized product are of
particular concern for silicone hydrogels, primarily due to the
inclusion of silicone-containing monomers which may tend to
separate from the hydrophilic comonomer. Suitable organic diluents
include, for example, monohydric alcohols, with C.sub.6-C.sub.10
straight-chained aliphatic monohydric alcohols such as n-hexanol
and n-nonanol being especially preferred; diols such as ethylene
glycol; polyols such as glycerin; ethers such as diethylene glycol
monoethyl ether; ketones such as methyl ethyl ketone; esters such
as methyl enanthate; and hydrocarbons such as toluene. Preferably,
the organic diluent is sufficiently volatile to facilitate its
removal from a cured article by evaporation at or near ambient
pressure. Generally, the diluent is included at five to sixty
percent by weight of the monomeric mixture, with ten to fifty
percent by weight being especially preferred.
[0131] The cured lens is then subjected to solvent removal, which
can be accomplished by evaporation at or near ambient pressure or
under vacuum. An elevated temperature can be employed to shorten
the time necessary to evaporate the diluent. The time, temperature
and pressure conditions for the solvent removal step will vary
depending on such factors as the volatility of the diluent and the
specific monomeric components, as can be readily determined by one
skilled in the art. According to a preferred embodiment, the
temperature employed in the removal step is preferably at least
50.degree. C., for example, 60 to 80.degree. C. A series of heating
cycles in a linear oven under inert gas or vacuum may be used to
optimize the efficiency of the solvent removal. The cured article
after the diluent removal step should contain no more than twenty
percent by weight of diluent, preferably no more than five percent
by weight or less.
[0132] Following removal of the organic diluent, the lens is next
subjected to mold release and optional machining operations. The
machining step includes, for example, buffing or polishing a lens
edge and/or surface. Generally, such machining processes may be
performed before or after the article is released from a mold part.
Preferably, the lens is dry released from the mold by employing
vacuum tweezers to lift the lens from the mold, after which the
lens is transferred by means of mechanical tweezers to a second set
of vacuum tweezers and placed against a rotating surface to smooth
the surface or edges. The lens may then be turned over in order to
machine the other side of the lens.
[0133] Subsequent to the mold release/machining operations, the
lens is subjected to surface treatment according to the present
invention, as described above, including the attachment of the
hydrophilic reactive polymer chains.
[0134] Subsequent to the step of surface treatment, the lens may be
subjected to extraction to remove residuals in the lenses.
Generally, in the manufacture of contact lenses, some of the
monomer mix is not fully polymerized. The incompletely polymerized
material from the polymerization process may affect optical clarity
or may be harmful to the eye. Residual material may include
solvents not entirely removed by the previous solvent removal
operation, unreacted monomers from the monomeric mixture, oligomers
present as by-products from the polymerization process, or even
additives that may have migrated from the mold used to form the
lens.
[0135] Conventional methods to extract such residual materials from
the polymerized contact lens material include extraction with an
alcohol solution for several hours (for extraction of hydrophobic
residual material) followed by extraction with water (for
extraction of hydrophilic residual material). Thus, some of the
alcohol extraction solution remains in the polymeric network of the
polymerized contact lens material, and should be extracted from the
lens material before the lens may be worn safely and comfortably on
the eye. Extraction of the alcohol from the lens can be achieved by
employing heated water for several hours. Extraction should be as
complete as possible, since incomplete extraction of residual
material from lenses may contribute adversely to the useful life of
the lens. Also, such residuals may impact lens performance and
comfort by interfering with optical clarity or the desired uniform
hydrophilicity of the lens surface. It is important that the
selected extraction solution in no way adversely affects the
optical clarity of the lens. Optical clarity is subjectively
understood to be the level of clarity observed when the lens is
visually inspected.
[0136] Subsequent to extraction, the lens is subjected to hydration
in which the lens is fully hydrated with water, buffered saline, or
the like. When the lens is ultimately fully hydrated (wherein the
lens typically may expand by 10 to about 20 percent or more), the
coating remains intact and bound to the lens, providing a durable,
hydrophilic coating which has been found to be resistant to
delamination.
[0137] Following hydration, the lens may undergo cosmetic
inspection wherein trained inspectors inspect the contact lenses
for clarity and the absence of defects such as holes, particles,
bubbles, nicks, tears. Inspection is preferably at 10.times.
magnification. After the lens has passed the steps of cosmetic
inspection, the lens is ready for packaging, whether in a vial,
plastic blister package, or other container for maintaining the
lens in a sterile condition for the consumer. Finally, the packaged
lens is subjected to sterilization, which sterilization may be
accomplished in a conventional autoclave, preferably under an air
pressurization sterilization cycle, sometime referred to as an
air-steam mixture cycle, as will be appreciated by the skilled
artisan. Preferably the autoclaving is at 100.degree. C. to
200.degree. C. for a period of 10 to 120 minutes. Following
sterilization, the lens dimension of the sterilized lenses may be
checked prior to storage.
[0138] Objects and advantages of this invention are further
illustrated by the following examples, but the particular materials
and amounts thereof recited in these examples, as well as other
conditions and details should not be construed at unduly limit this
invention.
EXAMPLE 1
[0139] This example discloses a representative silicone hydrogel
lens material used as a coating substrate in the following
Examples. The formulation for the material is provided in Table 1
below.
1 TABLE 1 Component Parts by Weight TRIS-VC 55 NVP 30
V.sub.2D.sub.25 15 VINAL 1 n-nonanol 15 Darocur 0.2 tint agent
0.05
[0140] The following materials are designated above:
2 TRIS-VC tris(trimethylsiloxy)silylpropyl vinyl carbamate NVP
N-vinyl pyrrolidone V.sub.2D.sub.25 a silicone-containing vinyl
carbonate as previously described in U.S. Pat. No. 5,534,604. VINAL
N-vinyloxycarbonyl alanine Darocur Darocur-1173, a UV initiator
tint agent 1,4-bis[4-(2-methacryloxyethyl)phenylamino]
anthraquinone
EXAMPLE 2
[0141] This Example illustrates a process for preparation of a
contact lens prior to surface modification of a contact lens
according to the present invention. Silicone hydrogel lenses made
of the formulation of Example 1 above were cast-molded from
polypropylene molds. Under an inert nitrogen atmosphere, 45-.mu.l
of the formulation was injected onto a clean polypropylene concave
mold half and covered with the complementary polypropylene convex
mold half The mold halves were compressed at a pressure of 70 psi
and the mixture was cured for about 15 minutes in the presence of
UV light (6-11 mW/cm.sup.2 as measured by a Spectronic UV meter).
The mold was exposed to UV light for about 5 additional minutes.
The top mold half was removed, and the lenses were maintained at
60.degree. C. for 3 hours in a forced air oven to remove n-nonanol.
Subsequently, the lens edges were ball buffed for 10 seconds at
2300 rpm with a force of 60 g.
EXAMPLE 3
[0142] This example illustrates the synthesis of the hydrophilic
reactive copolymer involving a 80/20 by weight percent ratio of
monomers (DMA/VDMO) employing the ingredients in Table 2 below:
3TABLE 2 Reagents Amount (g) Amount (m) Dimethylacrylamide (DMA) 16
g 0.1614 Vinyl-4,4-dimethyl-2-oxazolin-5-one 4 g 0.0288 (VDMO)
VAZO-64 initiator 0.031 g 0.1 percent Toluene 200 ml --
[0143] All ingredients except VAZO-64 were placed in a 500-ml
round-bottom flask equipped with a magnetic stirrer, condenser,
argon blanket, and thermo-controller. The above was de-aerated with
argon for 30 min. After VAZO-64 was added, the solution was heated
to 60.degree. C. and maintained for 50 hrs. After the reaction was
complete as monitored by FTIR (Fourier Transform Infrared
spectroscopy), the solution was slowly added to 2500 ml of diethyl
ether to precipitate the polymer. The mixture was stirred 10 min,
allowed to settle 10 min, and filtered. The precipitate was dried
under vacuum at 30 to 35.degree. C. overnight, and the molecular
weight determined to be Mn=19448, Mw=43548 and Pd=2.25, all based
on polystyrene standards. (Pd refers to polydispersity.)
EXAMPLE 4
[0144] This Example illustrates the synthesis of a prepolymer of
N,N-dimethylacrylamide that is used in making a macromonomer (or
"macromer") for eventual use in a reactive hydrophilic polymer
according to the present invention. The prepolymer is made
according to the following reaction scheme. 16
[0145] Reagents DMA (200 g, 2.0 moles), mercaptoethanol (3.2 g,
0.041 moles), AIBN (Vazo-64 in the amount 3.3 g, 0.02 moles) and
tetrahydrofuran (1,000 ml) were combined in a two liter round
bottom flask fitted with a magnetic stirrer, condenser, thermal
controller and a nitrogen inlet. Nitrogen gas was bubbled through
the solution for one half-hour. The temperature was increased to
60.degree. C. for 72 hours under a passive blanket of nitrogen. The
polymer was precipitated from the reaction mixture with 20 liters
of ethyl ether (171.4 g of polymer was isolated). A sample
submitted for SEC (size exclusion chromatography) analysis gave a
Mn=3711, Mw=7493, and Pd=2.02.
EXAMPLE 5
[0146] This Example illustrates the synthesis of a macromer of DMA
using the prepolymer of Example 4 which macromonomer is used to
make the hydrophilic reactive polymer of Examples 6 and 8 below,
which macromonomer is made according to the following reaction
scheme: 17
[0147] The prepolymer from Example 4 (150 g, 0.03 moles),
isocyanatoethylmethacrylate (IEM, 5.6 g, 0.036 moles),
dibutyltindilaurate (0.23 g, 3.6.times.10.sup.-5 moles),
tetrahydrofuran (THF, 1000 ml) and 2,6-di-tert-butyl-4-methyl
phenol (BHT, 0.002 g, 9.times.10.sup.-6 moles) were combined under
a nitrogen blanket. The mixture was heated to 35.degree. C. with
good stirring for seven hours. Heating was stopped, and the mixture
was allowed to stir under nitrogen overnight. Several ml of
methanol were added to react with any remaining IEM. The
macromonomer was then collected after precipitation from a large
volume (16 liters) of ethyl ether. The solid was dried under house
vacuum (yield 115 g). Size exclusion chromatography of the polymer
verses polystyrene standards gave the following results: Mn=2249,
Mw=2994, and Pd=1.33.
EXAMPLE 6
[0148] This Example illustrates the preparation of a
DMA/DMA-mac/VDMO polymer which may be used to form a coating
according to the present invention. Dimethylacrylamide (DMA) in the
amount of 16 g (0.1614 mole), vinyl-4,4-dimethyl-2-oxazolin-5-one
(VDMO) in the amount of 2 g (0.0144 mole), dimethylacrylamide
macromer (DMA-mac) as prepared in Example 5, in the amount of 2 g
(0.0004 mole), and 200 ml of toluene were placed in a 500-ml
round-bottom flask equipped with a magnetic stirrer, condenser,
argon blanket, and temperature controller. The solution was
de-aerated with argon for 30 min. Then 0.029 g (0.1 mole %) of
VAZO-64 was added and the reaction heated to 60.degree. C. for 50
hrs. After the reaction was complete (monitored by FTIR), the
solution was slowly added to 2500 ml of ethyl ether to precipitate
the polymer. After the addition was complete, the mixture was
stirred 10 min, allowed to settle 10 min, and filtered. The
precipitate was dried under house vacuum at 30 to 35.degree. C.
overnight. The dried polymer was sampled for analysis by gel
permeation chromatography, bottled and stored in a desiccator.
EXAMPLE 7
[0149] This Example illustrates the preparation of a DMA/PEOMA/VDMO
polymer usable to coat a silicone substrate according to the
present invention. Dimethylacrylamide, in the amount of 12 g
(0.1211 mole), vinyl-4,4-dimethyl-2-oxazolin-5-one in the amount of
4 g (0.0288 mole), and 4 g (0.0036 mole) PEO methacrylate (PEOMA),
which monomer has a MW of 1000, and 200 ml of toluene were placed
in a 500 ml round-bottom flask equipped with a magnetic stirrer,
condenser, argon blanket, and temperature controller. The solution
was de-aerated with argon for 30 min. Then 0.025 g (0.1 mole %) of
VAZO-64 was added, and the reaction heated to 60.degree. C. for 50
hrs. After the reaction was complete (monitored by FTIR), the
solution was slowly added to 2500 ml of ethyl ether to the polymer.
After the addition was complete, the mixture was stirred 10 min,
allowed to settle 10 min, and filtered. The precipitate was dried
under house vacuum at 30 to 35.degree. C. overnight. The dried
polymer was sampled for analysis by gel permeation chromatography,
bottled and stored in a desiccator.
EXAMPLE 8
[0150] This Example illustrates the synthesis of a hydrophilic
reactive polymer having a brush or branched structure with DMA
chains pendent from the backbone of the polymer. The polymer
consisted of the combination of the DMA macromonomer, glycidyl
methacrylate, and DMA monomer, prepared as follows. To a reaction
flask were added distilled N,N-dimethylacrylamide (DMA, 32 g, 0.32
moles), DMA macromer from Example 5 in the amount of 4 g (0.0008
moles), distilled glycidyl methacrylate (GM, 4.1 g, 0.029 moles),
Vazo-64 (AIBN, 0.06 g, 0.00037 moles) and toluene (500 ml). The
reaction vessel was fitted with a magnetic stirrer, condenser,
thermal controller, and a nitrogen inlet. Nitrogen was bubbled
through the solution for 15 min to remove any dissolved oxygen. The
reaction flask was then heated to 60.degree. C. under a passive
blanket of nitrogen for 20 hours. The reaction mixture was then
added slowly to 4 liters of ethyl ether with good mechanical
stirring. The reactive polymer precipitated and was collected by
vacuum filtration. The solid was placed in a vacuum oven at
30.degree. C. overnight to remove the ether, leaving 33.2 g of
reactive polymer (83% yield). The reactive polymer was placed in a
desicciator for storage until use.
EXAMPLE 9
[0151] This example illustrates the synthesis of a
vinylpyrrrolidone-co-4-- vinylcyclohexyl-1,2-epoxide polymer
(NVP-co-VCH) useful to coat a silicone substrate according to the
present invention. The polymer was prepared based on the following
reaction scheme: 18
[0152] To a 1 liter reaction flask were added distilled
N-vinylpyrrolidone (NVP, 53.79 g, 0.48 moles),
4-vinylcyclohexyl-1,2-epoxide (VCHE, 10.43 g, 0.084 moles), Vazo-64
(AIBN, 0.05 g, 0.0003 moles) and THF (600 ml). The reaction vessel
was fitted with a magnetic stirrer, condenser, thermal controller,
and a nitrogen inlet. Nitrogen was bubbled through the solution for
15 min to remove any dissolved oxygen. The reaction flask was then
heated to 60.degree. C. under a passive blanket of nitrogen for 20
hrs. The reaction mixture was then added slowly to 6 liters of
ethyl ether with good mechanical stirring. The copolymer
precipitated and was collected by vacuum filtration. The solid was
placed in a vacuum oven at 30.degree. C. overnight to remove the
ether, leaving 21 g of reactive polymer (32% yield). The
hydrophilic reactive polymer was placed in a dessicator for storage
until use.
EXAMPLE 10
[0153] This Example illustrates the synthesis of a hydrophilic
reactive (linear) copolymer of DMA/GMA, which is used in Examples
13, 14, and 15 below, according to the following reaction scheme:
19
[0154] To a 1-liter reaction flask were added distilled
N,N-dimethylacrylamide (DMA, 48 g, 0.48 moles), distilled glycidyl
methacrylate (GM, 12 g, 0.08 moles), Vazo-64 (AIBN, 0.096 g, 0.0006
moles) and toluene (600 ml). The reaction vessel was fitted with a
magnetic stirrer, condenser, thermal controller, and a nitrogen
inlet. Nitrogen was bubbled through the solution for 15 min to
remove any dissolved oxygen. The reaction flask was then heated to
60.degree. C. under a passive blanket of nitrogen for 20 hours. The
reaction mixture was then added slowly to 6 liters of ethyl ether
with good mechanical stirring. The reactive polymer precipitated
and was collected by vacuum filtration. The solid was placed in a
vacuum oven at 30.degree. C. overnight to remove the ether leaving
50.1 g of reactive polymer (83% yield). The reactive polymer was
placed in a desicciator for storage until use.
EXAMPLE 11
[0155] This Example illustrates the synthesis of a water-soluble
reactive polymer of DMA/GMA/OFPMA, according to the following
reaction scheme: 20
[0156] To a 500 ml reaction flask were added distilled
N,N-dimethylacrylamide (DMA, 16 g, 0.16 moles), 1H, 1H,
5H-octafluoropentylmethacrylate (OFPMA, 1 g, 0.003 moles, used as
received), distilled glycidyl methacrylate (GM, 4 g, 0.028 moles)
Vazo-64 (AIBN, 0.03 g, 0.00018 moles) and toluene (300 ml). The
reaction vessel was fitted with a magnetic stirrer, condenser,
thermal controller, and a nitrogen inlet. Nitrogen was bubbled
through the solution for 15 minutes to remove any dissolved oxygen.
The reaction flask was then heated to 60.degree. C. under a passive
blanket of nitrogen for 20 hours. The reaction mixture was then
added slowly to 3 liters of ethyl ether with good mechanical
stirring. The reactive polymer precipitated and was collected by
vacuum filtration. The solid was placed in a vacuum oven at
30.degree. C. overnight to remove the ether leaving 19.3 g of
reactive polymer (92% yield). The reactive polymer was placed in a
desicciator for storage until use.
EXAMPLE 12
[0157] This Example illustrates the synthesis of a hydrophilic
reactive polymer of DMA/MAA, according to the following reaction
scheme: 21
[0158] To a 500 ml reaction flask were added distilled
N,N-dimethylacrylamide (DMA, 16 g, 0.16moles), methacrylic acid
(MAA, 4 g, 0.05 moles) Vazo-64 (AIBN, 0.033 g, 0.0002 moles) and
anhydrous 2-propanol (300 ml). The reaction vessel was fitted with
a magnetic stirrer, condenser, thermal controller, and nitrogen
inlet. Nitrogen was bubbled through the solution for 15 minutes to
remove any dissolved oxygen. The reaction flask was then heated to
60.degree. C. under a passive blanket of nitrogen for 72 hours. The
reaction mixture was then added slowly to 3 liters of ethyl ether
with good mechanical stirring. The reactive polymer precipitated
and was collected by vacuum filtration. The solid was placed in a
vacuum oven at 30.degree. C. overnight to remove the ether leaving
9.5 g of reactive polymer (48 % yield). The reactive polymer was
placed in a desicciator for storage until use.
EXAMPLE 13
[0159] This Example illustrates the surface treatment of Balafilcon
A contact lenses (PureVision.RTM. lenses, commercially available
from Bausch & Lomb, Inc., Rochester, N.Y.) made from the
material of Example 1, which surface treatment employed the
hydrophilic reactive polymers made from Example 10 above, according
to the following reaction scheme: 22
[0160] A solution of reactive polymer of Example 10 (10.0 g per
1000 ml of water) was prepared. Lenses were extracted with three
changes of 2-propanol over a four-hour period and then with three
changes of water at one-hour intervals. Lenses (36 samples) were
then placed in the solution of reactive polymer. One drop of
methyldiethanolamine was added to catalyze the reaction. The lenses
were put through one 30-minute autoclave cycle.
EXAMPLE 14
[0161] This Example illustrates the surface treatment of an RGP
Lens Surface according to the present invention, as shown below.
The lens was a Quantum.RTM. II RGP contact lens, commercially
available from Bausch & Lomb, Inc. 23
[0162] A solution of reactive polymer of Example 10 (5.0 g per 100
ml of water) was prepared. Lenses (20 samples) were then placed in
the solution of reactive polymer with two (2) drops of
triethanolamine and heated to 55.degree. C. for one (1) hour. The
surface-coated lenses were then rinsed off twice with purified
water and allowed to dry. A drop of water placed on an untreated
lens would bead up and roll off the surface while a drop of water
was placed on the treated lens spread completely, wetting the lens
surface.
[0163] X-ray Photo Electron Spectroscopy (XPS) data was obtained at
the Surface Science lab within Bausch and Lomb. A Physical
Electronics [PHI] Model 5600 XPS was used for the surface
characterization. This instrument utilized a monochromated Al anode
operated a 300 watts, 15 kV and 20 milliamps. The base pressure of
the instrument was 2.0.times.10.sup.-10 torr and during operation
the pressure was 5.0.times.10.sup.-8 torr. This instrument made use
of a hemispherical analyzer. The instrument had an Apollo
workstation with PHI 8503A version 4.0A software. The practical
measure for sampling depth for this instrument at a sampling angle
of 45.degree. was 74 .ANG..
[0164] Each specimen was analyzed utilizing a low-resolution survey
spectra (0-1100 eV) to identify the elements present on the sample
surface (10-100 .ANG.). Surface elemental compositions were
determined from high-resolution spectra obtained on the elements
detected in the low-resolution survey scans. Those elements
included oxygen, nitrogen, carbon, silicon and fluorine.
Quantification of elemental compositions was completed by
integration of the photoelectron peak areas after sensitizing those
areas with the instrumental transmission function and atomic cross
sections for the orbitals of interest. The XPS data for the coated
lenses and controls are given in Table 3 below.
4TABLE 3 Sample O N C Si F Lens Posterior Average 22.3 4.8 54.4
10.3 10.9 Std dev Lens Anterior Average 19.1 6.7 63.4 2.7 8.1 std
dev 0.6 0.3 1.1 0.6 0.7 Quantum .RTM. II Control Average 18.7 0.0
56.1 5.2 20.0 (post & ant are the std dev 0.5 0.0 0.7 0.3 0.4
same) Theoretical Atomic 17 12 71 0 0 Concentrations for DMA-co-GMA
Reactive Polymer
EXAMPLE 15
[0165] This Example illustrates another surface treatment of an
Quantum.RTM. II RGP contact lens, commercially available from
Bausch & Lomb, Inc., according to the following reaction
sequence: 24
[0166] A solution of reactive polymers of Example 10 and Example 12
above (2.5 g of each polymer per 100 ml of water) was prepared. The
mixture of polymers was used in an attempt to build a thicker
polymer coating via a layering effect. Lenses (20 samples) were
then placed in the solution of reactive polymer with two drops of
triethanolamine and heated to 55.degree. C. for one hour. The
surface-coated lenses were then rinsed off twice with purified
water and allowed to dry. A drop of water placed on an untreated
lens would bead up and roll off the surface while a drop of water
placed on the treated lens spread completely wetting the lens
surface. Atomic Force Microscopy (AFM) analysis suggests that the
combination of polymers gave a thicker polymer coating. Comparisons
between a Quantum.RTM. II lens with no polymer coating (FIG. 1),
the polymer coating of Example 14 (FIG. 2), and the coating of this
Example 15 (FIG. 3) are shown in FIGS. 1 to 3.
[0167] X-ray Photo Electron Spectroscopy (XPS) data was obtained at
the Surface Science lab within Bausch and Lomb. A Physical
Electronics [PHI] Model 5600 XPS was used for the surface
characterization. This instrument utilized a monochromated Al anode
operated a 300 watts, 15 kV and 20 milliamps. The base pressure of
the instrument was 2.0.times.10.sup.-10 torr and during operation
the pressure was 5.0.times.10.sup.-8 torr. This instrument made use
of a hemispherical analyzer. The instrument had an Apollo
workstation with PHI 8503A version 4.0A software. The practical
measure for sampling depth for this instrument at a sampling angle
of 45.degree. was 74 .ANG..
[0168] Each specimen was analyzed utilizing a-low-resolution survey
spectra (0-1100 eV) to identify the elements present on the sample
surface (10-100 .ANG.). Surface elemental compositions were
determined from high-resolution spectra obtained on the elements
detected in the low-resolution survey scans. Those elements
included oxygen, nitrogen, carbon, silicon and fluorine.
Quantification of elemental compositions was completed by
integration of the photoelectron peak areas after sensitizing those
areas with the instrumental transmission function and atomic cross
sections for the orbitals of interest. The XPS data for the coated
lenses and controls are given in Table 4A below.
5TABLE 4A Sample O N C Si F Lens Posterior Average 18.8 8.0 67.6
3.7 2.6 Std dev Lens Anterior Average 18.4 4.2 62.8 4.1 10.5 std
dev 0.5 1.2 1.7 0.4 3.1 Quantum .RTM. II Control Average 18.7 0.0
56.1 5.2 20.0 (post & ant are the std dev 0.5 0.0 0.7 0.3 0.4
same) Theoretical Atomic 17 12 71 0 0 Concentrations for DMA-co-GMA
Reactive Polymer
EXAMPLE 16
[0169] This Example illustrates the surface treatment of Balafilcon
A contact lenses (PureVision.RTM. lenses, commercially available
from Bausch & Lomb, Inc., Rochester, N.Y.) made from the
material of Example 1, which surface treatment employed the
hydrophilic reactive polymers made from Example 11 above, according
to the following reaction scheme: 25
[0170] Two solutions of the reactive polymer of Example 11 were
prepared (see Table 4B below). Lenses were extracted in 2-propanol
for 4 hours and then placed in purified water for 10 minutes. The
water bath was then changed, and the lenses were allowed to soak
for an additional 10 minutes. Lenses (30 samples) were then placed
in each solution of reactive polymer with one drop of
methyldiethanolamine to catalyze the reaction. The lenses were put
through one 30-minute autoclave cycle. The solution in the vials
was then replaced with purified water twice, and the samples were
again autoclaved. This procedure was used to remove any hydrophilic
polymer not chemically bonded to the lens.
6TABLE 4B Sample Polymer Concentration No. Lenses treated A 1.0%
(2.5 g/250 ml H.sub.2O) 30 B 2.0% (5 g/250 ml H.sub.2O) 30 Control
None 30
[0171] The atomic force microscopy (AFM) images of the control is
shown in FIG. 4. FIG. 5 and FIG. 6 show the surface of Samples A
and B, respectively. The hydrophilic coating is clearly shown in
FIGS. 5 and 6 compared to the surface image of the Control Sample.
Elemental analysis by XPS also indicates that the material surface
has been modified. The XPS data was obtained at the Surface Science
lab within Bausch and Lomb. A Physical Electronics [PHI] Model 5600
XPS was used for the surface characterization. This instrument
utilized a monochromated Al anode operated a 300 watts, 15 kV and
20 milliamps. The base pressure of the instrument was
2.0.times.10.sup.-10 torr and during operation the pressure was
5.0.times.10.sup.-8 torr. This instrument made use of a
hemispherical analyzer. The instrument had an Apollo workstation
with PHI 8503A version 4.0A software. The practical measure for
sampling depth for this instrument at a sampling angle of
45.degree. was 74 .ANG..
[0172] Each specimen was analyzed utilizing a low-resolution survey
spectra (0-1100 eV) to identify the elements present on the sample
surface (10-100 .ANG.). Surface elemental compositions were
determined from high-resolution spectra obtained on the elements
detected in the low-resolution survey scans. Those elements
included oxygen, nitrogen, carbon, silicon and fluorine.
Quantification of elemental compositions was completed by
integration of the photoelectron peak areas after sensitizing those
areas with the instrumental transmission function and atomic cross
sections for the orbitals of interest. The XPS data is given in
Table 4C below.
7TABLE 4C Sample O1s N1s C1s Si2p F1s Control Posterior Average
17.7 7.2 66.9 8.1 0.0 std dev 0.9 0.2 0.8 0.3 0.0 Control Anterior
Average 17.9 7.0 66.9 8.2 0.0 std dev 0.6 0.6 0.7 0.4 0.0 A
Posterior Average 17.9 8.9 69.5 1.8 2.0 std dev 0.3 0.2 0.6 0.6 0.2
A Anterior Average 17.7 9.1 69.7 1.7 1.9 std dev 0.3 0.3 0.8 0.3
0.2 B Posterior Average 18.0 8.9 69.9 1.2 2.1 std dev 0.3 0.5 1.0
0.1 0.4 B Anterior Average 17.8 8.8 70.0 1.3 2.0 std dev 0.2 0.3
0.6 0.3 0.0 Theoretical Atomic Conc. 17.1 11.0 70.1 0.0 1.8
DMA-co-OFPMA-co-GMA From Example 11
EXAMPLE 17
[0173] This Example illustrates improved inhibition of lipid
deposition for the Balafilcon A lenses (PureVision.RTM. lenses)
coated by reaction with various hydrophilic reactive polymers
according to the present invention. Sample E lenses was coated
using a 1% solution of the DMA/OFPMA/GM copolymer of Example 11,
and Sample EE lenses was coating using a 2% solution of the same
polymer. Samples F and FF lenses were respectfully coated using 1%
and 2% solutions of the DMA/GM copolymer of Example 10. The lenses
were placed in an aqueous solution of the reactive hydrophilic
polymer with a catalyst and run through one autoclave cycle. The
lenses were then rinsed in HPLC grade water, placed in fresh HPLC
water, and autoclaved for a second time. The control lenses (no
surface treatment) were placed in HPLC water and autoclaved. One
control lens was the Balafilicon A lens prior to any surface
treatment. A second control lens was the commercial PureVision.RTM.
lens with a oxidative plasma surface treatment. For the lipid
analysis, Gas Chromatography (GC) was employed, including an HP
Ultra 1 column with an FID detector and He carrier gas. In the in
vitro lipid deposition protocol, six lenses were subject to
deposition for each of the lens types tested, employing a lipid mix
of palmitic acid methyl ester, cholesterol, squalene and mucin in
MOPS buffer. Mucin was utilized as a surfactant to aid in the
solubilization of the lipids. The above lipid mix in the amount of
1.5 ml was added to the test lenses, which were subject to
deposition in a 37.degree. C. shaking-water bath for 24 hours. The
lenses were then removed from the water bath, rinsed with ReNu.RTM.
Saline to remove any residual deposition solution, and placed in
glass vials for extraction. A three hour 1:1 CHCl.sub.3/MeOH
extraction was subsequently followed by a three hour hexane
extraction. Extracts were then combined and run on the GC
chromatograph. Standard solutions of each of the lipids in the
deposition mix were made in 1:1 CHCl.sub.3/MeOH and run on the GC
for determination of the concentration of lipid extracted from the
lenses. The in vitro lipid deposition profiles for the lenses
tested, using the protocol above, are shown in Table 5 below.
8 TABLE 5 Average Lipid Sample Concentration* (.mu.g) E 39.9 EE
36.7 F 51.2 FF 39.6 Plasma-Oxidation 117 Control
No-Surface-Treatment 243.3 Control lenses *The average represents
the deposition profile for 6 deposited lenses.
[0174] The results indicate that lenses coated according to the
present invention can exhibit reduced lipid deposition, a
particularly advantageous property for continuous-wear hydrogel
lenses.
[0175] Many other modifications and variations of the present
invention are possible in light of the teachings herein. It is
therefore understood that, within the scope of the claims, the
present invention can be practiced other than as herein
specifically described.
* * * * *