Polymer compositions for contact lenses

An improved hydrogel formed from hydrated polymerization products of monomer mixtures containing a major amount of at least one hydrophilic monomer and a strengthening monomer wherein the strengthening monomer is 2-hydroxycyclohexyl methacrylate. Contact lenses made from the hydrogels are also disclosed.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to copolymers and hydrogels useful as contact lens 
materials. This invention also relates to hydrogel shaped articles, 
preferably contact lenses, which are made from hydrated polymerization 
products of monomer mixtures containing a major amount of at least one 
hydrophilic monomer and a strengthening monomer. 
2. Description of the Related Art 
The use of hydrogels to make contact lenses has been known, since at least 
as early as Wichterle, et al., U.S. Pat. No. 3,220,960 which discloses 
hydrogels involving a hydrated polymer of an hydroxyalkyl acrylate or 
methacrylate crosslinked with a corresponding diester. Since then a 
variety of hydrogel materials have been developed, ranging from low-water 
hydrogels such as poly(2-hydroxyethyl methacrylate) with a water content 
of about 39% to mid-water hydrogels having a water content of about 40 to 
60%, to high-water hydrogels having a water content of about 60 to 90%. 
Examples of high-water hydrogels include poly(N-vinyl pyrrolidone) (NVP) or 
poly(N,N-dimethylacrylamide)(DMA). Homopolymers of DMA and NVP possess 
water contents in excess of 90%. In a copolymer system, the water content 
of a NVP or DMA based hydrogel can vary widely depending on the 
concentration of NVP or DMA. Higher concentrations of NVP or DMA result in 
a significant increase in water content. Most commercial hydrogels derived 
from NVP and DMA have a water content in the 70% to 80% range. 
A desirable benefit of high water lenses is their higher oxygen 
permeability. This relates to the ability of the lens material to 
transport oxygen to the cornea of the eye. Oxygen permeability can be 
increased by increasing the water content. However, increasing water 
content undesirably affects other mechanical properties of the lens, such 
as decreasing the tensile and tear strength of the lens. Thus, a major 
drawback of high water content hydrogels is the cured copolymers are often 
fragile. During patient usage, high water lenses have a tendency to fold 
and frequently tear during handling. 
One approach to solving these problems involves incorporating a 
"strengthening monomer", i.e. a monomer that improves the tensile and tear 
strength of the lens. U.S. Pat. Nos. 5,006,622, 5,236,969, 5,270,418 
(Kunzler et al.) and 5,298,533 (Nandu et al.) disclose a class of 
strengthening hydrophobic monomers which can be copolymerized with 
hydrophilic monomers for hydrogel contact lenses. These strengthening 
monomers include: 4-t-butyl-2-hydroxycyclohexyl methacrylate (TBE); 
4-t-butyl-2-hydroxycyclopentyl methacrylate; 4-t-butyl-2-hydroxycyclohexyl 
methacrylamide; 6-isopentyl-3-hydroxycyclohexyl methacrylate; and 
2-isohexyl-5-hydroxycyclopentyl methacrylamide. The major drawback of 
these monomers, however, is that they are not commercially available. They 
require several synthetic steps in their preparation that significantly 
increase the cost of the resultant lens. While these strengthening 
monomers did adequately improve the physical parameters of high water 
lenses, it was the object of this invention to provide an alternate 
monomer that would also perform as a strengthener while either being 
commercially available or simple to synthesize, resulting in reduced cost 
per lens. 
SUMMARY OF THE INVENTION 
It has now been found that the mechanical properties of contact lens 
materials can be improved by the incorporation of 2-hydroxycyclohexyl 
methacrylate (2HCHM) as a strengthening agent in the monomer mixtures. Its 
inclusion effectively improves physical properties such as tear strength 
and tensile strength; it is compatible with the hydrophilic monomer; it is 
easy to synthesize; and the resultant copolymers provide optically clear 
hydrogels which exhibit a desired combination of properties including a 
relatively high water content and oxygen permeability, and hydrolytic 
stability. 
The invention is broadly applicable to contact lens materials: hydrogels 
prepared from a monomer mixture employing 2HCHM and a hydrophilic monomer. 
The water content of the hydrogel is preferably within the range of about 
40 to about 90%, more preferably within the range of about 50 to about 80% 
and still more preferably between about 55 to about 70%. The modulus is 
preferably in the range of about 20 to about 100 g/mm.sup.2. Preferred 
hydrophilic monomers are N,N-dialkyl(meth)acrylamide, 2-hydroxyethyl 
methacrylate (HEMA), glyceryl methacrylate, and N-vinyl pyrrolidone (NVP). 
As previously noted in U.S. Pat. No. 5,298,533, incorporation of a vinyl 
lactam, such as NVP, in the monomer mixture as the hydrophilic monomer can 
affect the processability of the monomeric mixture. The cure time is 
increased with heat generally required to complete the polymerization. 
Another difficulty arises from phase separation which can occur when vinyl 
lactams are admixed with monomers having (meth)acrylate or 
(meth)acrylamide functionality. It has been found that monomeric mixtures 
comprising hydrophilic and strengthening monomers of this invention can be 
cured effectively under ultraviolet light at room temperature and without 
encountering deleterious effects from phase separation of the monomers. 
The copolymers of the present invention generally have a much lower modulus 
of elasticity than the copolymers disclosed in U.S. Pat. No. 5,006,622. 
This is very important in that materials of lower modulus generally 
exhibit improved comfort. Despite having the lower modulus of elasticity, 
the copolymers of this invention still exhibit sufficient mechanical 
strength due to the high tear strength. Without wishing to be bound by any 
particular theory of operability, the Applicant believes that the 
cyclohexyl group generates a more rigid polymer, improving the mechanical 
properties and the secondary hydroxyl group improves compatibility with 
hydrophilic monomers, reducing the occurrence of phase separation. 
Another benefit of 2HCHM over the strengthening monomer of U.S. Pat. No. 
5,006,622, 4-t-butyl-2-hydroxycyclohexyl methacrylate (TBE), is the ease 
of synthesis. 2HCHM is much easier to make than TBE requiring only one 
synthetic step, as compared to three for TBE. The starting material for 
2HCM, cyclohexyl epoxide, is commercially available, dramatically reducing 
the synthetic and subsequent lens costs. 
DETAILED DESCRIPTION OF THE INVENTION 
A hydrogel is a hydrated crosslinked polymeric system that contains water 
in an equilibrium state. The physical properties of hydrogels can vary 
widely and are mostly determined by their water content. Hydrogels may 
contain 10% to 90% water by weight and exhibit excellent biocompatibility 
and as such are used for soft biomedical applications. Commercial success 
for hydrogels has been found in the field of ophthalmology, most 
particularly as contact lenses. 
Conventional hydrogel contact lenses are prepared by polymerizing a monomer 
mixture containing at least one hydrophilic monomer. The term "hydrophilic 
monomer" as used here denotes a monomer whose homopolymers have the 
ability to absorb water. The term is not intended to include monomers 
merely because they have a hydrophilic group. A monomer is "hydrophilic" 
only if its homopolymer absorbs water. 
The term "strengthening monomer" as used here relates to a monomer which 
can be polymerized with hydrophilic monomers in order to provide polymeric 
materials with improved physical properties, particularly tear and tensile 
strength. It is understood that said additional hydrophilic monomer is 
defined as different from, or exclusive of, the strengthening monomer. 
The strengthening monomer of this invention is 2HCHM. Previously, 2HCHM had 
been disclosed as a hydrophilic monomer to be copolymerized with a 
strengthening agent such as TBE ('622). Further investigation of this 
monomer shows that it is actually incapable of absorbing any significant 
amount of water and should therefore be considered hydrophobic. 
The strengthening monomer of this invention is preferably present at 5 to 
45 parts by weight of total monomeric components, more preferably at 7 to 
35 parts by weight and still more preferably, at 15 to 35 parts by weight. 
Mechanical properties such as tear strength can be significantly improved 
by employing at least 5 parts by weight of the strengthening monomer. When 
a higher tear strength is desired, it is preferred that the strengthening 
monomer is included in at least 15 parts by weight of total monomeric 
components. 
The monomeric mixtures from which the copolymers are prepared may include 
at least one hydrophilic monomer known in the art as useful for contact 
lens materials. The selection of hydrophilic monomers for use in this 
invention is not narrowly critical. Representative hydrophilic monomers 
include: unsaturated carboxylic acids, such as (meth)acrylic acids; 
(meth)acrylic substituted alcohols, vinyl lactams, and (meth)acrylamides 
(as used herein, the term "(meth)" indicates optional methyl substitution. 
Thus, a term such as "(meth)acrylate" designates both acrylates and 
methacrylates). Specific examples of hydrophilic monomers include 
methacrylamide, N-methylmethacrylamide, N,N-dimethylacrylamide, 
N,N-dimethylmethylacrylamide, glyceryl methacrylate, 
N-(2-hydroxyethyl)methacrylamide, N-methacryloyl glycine; and 
(2-hydroxy-3-methacryloylpropyl)-4-methoxy phenylether. More preferred 
monomers are N,N-dimethylacrylamide, N-vinyl-2-pyrrolidone (NVP), and 
2-hydroxyethyl methacrylate (HEMA), 
It is preferred that the hydrophilic monomer (a term which is meant to 
include mixtures of hydrophilic monomers) is included in the monomeric 
mixture at 50-95 parts by weight of total monomeric components, with 60-90 
parts by weight being especially preferred. According to preferred 
embodiments, the monomeric mixture includes at least 60 parts by weight, 
and more preferably at least 65 parts by weight, of total hydrophilic 
monomeric components so that the resultant copolymer is predominantly 
hydrophilic and wettable for use as a contact lens material. 
The monomeric mixture usually includes a crosslinking agent (a crosslinker 
being defined as a monomer having multiple polymerizable functionalities), 
although one of the hydrophilic monomers may function as the crosslinker. 
Crosslinking agents are known in the art, and representative crosslinking 
agents include allyl methacrylate and ethylene glycol dimethacrylate 
(EGDMA). For other acrylic-containing, vinyl-containing and/or 
styrene-containing hydrophilic monomers, crosslinkers such as 
methacryloxyethyl vinyl carbonate (HEMAVC), 4-vinylphenyl vinyl carbonate, 
and 4-vinylphenyl carbamate are used. 
Minor amounts of a polymerization initiator may also be included. The 
initiator is preferably a free radical ultraviolet polymerization 
initiator such as benzoin methyl ether (BME). Other initiators are known 
in the art. 
A diluent may be added to the monomeric components, wherein the diluent is 
defined as a substance which is substantially nonreactive with the 
monomers in the monomeric mixture. The diluent may be added to the 
monomeric mixture at 0 to 50 parts by weight, based on weight of monomeric 
components in the mixture, more preferably, at 5 to 40 parts by weight, 
with 10 to 30 parts by weight being more preferred. The diluent can serve 
to minimize any incompatibility of the components in the initial monomeric 
mixture and further alleviate any problems attributed to phase separation. 
Also, the diluent may lower the glass transition temperature of the 
reacting polymeric mixture which allows for a more efficient curing 
process. Water may be used as the diluent, or alternately, an organic 
diluent may be employed, including: monohydric alcohols, with C.sub.3 
-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 dipropylene 
glycol and diethylene glycol monobutyl ether; ketones, such as methyl 
ethyl ketone; esters, such as methyl enanthate, ethylene carbonate and 
glyceryl triacetate; and hydrocarbons. Other suitable diluents will be 
apparent to a person of ordinary skill in the art. 
An optional additive is a color additive or tint at minor amounts (0.006%). 
Many contact lens tints are known in the art. 
An especially preferred class of copolymers is produced by polymerizing a 
mixture containing: 
(a) 30 to 70 parts by weight of a hydrophilic monomer or mixture thereof; 
(b) 10 to 40 parts by weight of 2-hydroxycyclohexyl methacrylate; 
(c) 0.01 to 5 parts by weight of a suitable crosslinking monomer; and 
(d) 0.01 to 5 parts by weight of a polymerization initiator; 
wherein the amounts are based on 100 parts by weight of components (a), 
(b), (c), and (d). Optionally, a diluent is added to the mixture at 0 to 
50 parts by weight per 100 parts by weight of components (a), (b), (c), 
and (d). 
The present invention further includes a hydrogel shaped article in the 
form of a contact lens which is the hydrated polymerization product of the 
previously described monomeric mixtures. The copolymers of the present 
invention provide contact lenses which are hydrolytically stable, 
biologically compatible and optically clear. Hydrolytic stability 
indicates that the contact lenses do not undergo chemical degradation and 
maintain substantially the same water content over time. 
While the strengthening agent of this invention is broadly applicable to 
use in hydrogels, it is particularly applicable to hydrogel materials for 
mid- to high-water contact lenses. Preferably, the hydrated contact lenses 
have a water content of about 40-90%, more preferably 50-80%, and still 
more preferably 55-70%. It is also preferred that the lenses have a tear 
strength of at least 3.0 g/mm thickness to prevent damage to the lens from 
handling. 
Contact lenses of the present invention are made according to techniques 
well known by those of ordinary skill in the art. 
Inclusion of 2HCHM provides copolymers which could not otherwise be used 
for contact lens applications. Copolymers consisting of 
N,N-dimethylacrylamide (DMA)/ethylene glycol dimethacrylate (EGDMA) 
combinations do not have enough strength to permit testing of physical 
properties while DMA/2HCHM/EGDMA exhibit good physical properties. See 
Examples 2 and 3, below. The strengthening monomer is compatible with a 
variety of hydrophilic monomers and its incorporation produces copolymers 
having improved mechanical properties. 
The invention is further described by reference to the following examples, 
which are intended to be illustrative but not limiting of the present 
invention.

EXAMPLE 1 
Synthesis of 2-HCHM 
222.8 grams (g) cyclohexene oxide (Aldrich Chem. Co.), 390.8 g methacrylic 
acid (Rohm and Haas), 459.4 g triethylamine (Aldrich Chem. Co.), 0.24 g 
2,5-diphenyl-1,4-benzoquinone (Aldrich Chem. Co.) and 0.24 g cuprous 
chloride (Aldrich Chem. Co.) were added under dry air to a 2 liter round 
bottom flask equipped with a stir bar, water condenser, heating mantle and 
electronic heating unit equipped with a thermocouple. The reaction was 
heated to 90.degree. C. and monitored by gas chromotography (GC) for 
extent of reaction (the reaction was typically complete following a five 
hour reaction time-extent of reaction 90-95%). The unreacted methacrylic 
acid, triethylamine and cyclohexene epoxide was then removed by vacuum 
distillation at 90.degree. C. using a 20 cm Vigreux column and 
distillation head. The reaction was then diluted with 1500 mL of pentane 
and washed two times with 300 mL of IN NaOH brine solution (prepared by 
combining an equal volume of 2N NaOH with a saturated brine solution) and 
two times with a 2N HCl solution. The organic layer was collected, dried 
over MgSO.sub.4, and the pentane is removed using a rotoevaporator 
(40.degree. C./approximately 30 mm of Hg). After the pentane was removed, 
the crude 2-HCHM was purified by short-path vacuum distillation (boiling 
point 100.degree. C./0.2 mm Hg, 300 ppm of butylated hydroxy toluene was 
added as a polymerization inhibitor). The final yield of 2-HCHM was 
between 60% and 70% with a GC purity of 95% or greater. 
EXAMPLES 2 AND 3 
Comparative Examples A-C 
A series of mixtures were prepared from N,N-dimethylacrylamide (DMA), 
2-hydroxy cyclohexyl methacrylate (2HCHM), 2-hydroxyethyl methacrylate 
(HEMA) and a diluent. Examples 2, 3, A and C were prepared with glycerin 
while B was prepared with hexanol. The amounts of these components, with 
the percentages of the monomers in the composition are listed in Table 1. 
Additionally, the mixtures included ethylene glycol dimethacrylate (EGDMA) 
(0.34%), benzoin methyl ether (BME) (0.17%) and a color additive (0.006%). 
The resultant monomeric mixtures were cast between two silane-treated 
glass plates separated by Teflon.TM. gaskets having a thickness of about 
0.2 mm and cured under ultraviolet light at room temperature for 2 hours. 
The cured films were removed from the glass plates and extracted with 
water, followed by hydration in buffered saline. The modulus of elasticity 
and tear strength of the hydrated films were measured following modified 
ASTM-D 1708 and ASTM-D 1938 methods. 
The results are summarized in Table 1. 
TABLE 1 
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Example 
2 3 A B C 
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% DMA 50 55 15 20 20 
% HEMA -- -- 70 65 65 
% 2HCHM 35 30 -- -- -- 
% Diluent 15 15 15 15 15 
Modulus 45 20 25 11 23 
(g/mm.sup.2) 
Tear 10.0 4.0 2.9 3.7 2.7 
Strength 
(g/mm) 
% Water 66.1 72.6 55.2 64.9 61.9 
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These examples show that it is possible to achieve high water content 
materials with excellent mechanical properties. While a higher water 
content will give a higher oxygen permeability, one normally sees a 
dramatic effect in the tear strength. Examples 2 and 3 give high water 
content with low moduli and excellent tear strength. Example 2 and B have 
similar water content but example 2 exhibits a much better tear strength. 
EXAMPLE 4 
Contact Lens of the Invention 
A monomer mixture containing 50% DMA, 35% 2HCHM, and 15% glycerin was 
prepared. To this mixture was added 0.34% EGDMA, 0.17% BME and 0.01% of a 
color additive. Samples of this mixture were injected onto a polypropylene 
concave mold section (for the anterior lens surface), and then covered 
with a convex polypropylene mold section (for the posterior lens surface). 
After pressing the molds together, the mold assemblies containing monomer 
mix were exposed to UV light for 30 minutes at room temperature. The molds 
were opened mechanically, the cured contact lenses were released from the 
mold section in warm water, and then the lenses were extracted with water 
and hydrated in buffered saline. The mechanical properties of the lens 
lots were evaluated following the general procedure of Example 1. The 
lenses possessed a modulus of 70 g/mm.sup.2, a tensile strength 33 
g/mm.sup.2, a tear strength of 7.3 g/mm, 97% elongation and 61.6% water. 
While certain preferred embodiments have been described, it is understood 
that the invention is not limited thereto and modifications and variations 
would be evident to a person of ordinary skill in the art.