Hydrogel compositions using p-(2-hydroxyhexafluoroisopropyl) styrene as a comonomer

Hydrogel compositions characterized by a copolymer composition which includes a hydroxyfluoroalkylstyrene as a comonomer. The preferred comonomer compound is p-(2-hydroxyhexafluoroisopropyl)-styrene [HFIS].

BACKGROUND OF THE INVENTION 
This invention relates to novel hydrogels that contain as a comonomer a 
hydroxyfluoroalkylstyrene and in a most preferred embodiment 
p-(2-hydroxyhexafluoroisopropyl) styrene (HFIS). Hydrogels are usually 
defined as natural or synthetic polymeric systems that contain 
approximately from about 10% to about 90% water in an equilibrium state. 
In general the physical properties of hydrogels are determined to a large 
extent by their water content. Due to their excellent biocompatability 
there has been extensive interest in hydrogels as biomedical devices. Thus 
there have been investigations on the use of hydrogels as contact lenses, 
intrastromal implants, intraocular lenses, coatings on numerous devices, 
membranes of several types, tissue replacement, ureter prosthesis, breast 
augmentation, etc. To date, the most commercial success has been found in 
the field of ophthalmology, and most particularly, soft contact lenses. 
Hydrogel type contact lenses have been known, since at least as early as 
Wichterle et al, U.S. Pat. No. 3,220,960 which discloses a hydrogel which 
involves a hydrated polymer of an hydroxyalkyl acrylate or methacrylate 
cross-linked with a corresponding diester. Such gels may contain from 
about 10% to about 90% by weight water, preferably from about 30% to about 
50% by weight water. Of the monomers used to prepare such hydrogels, 
2-hydroxyethyl methacrylate is most commonly used. The equilibrium water 
content of lightly cross-linked poly (2-hydroxyethyl methacrylate) is 
about 40%. These hydrogels are often referred to as low water content 
hydrogels. 
Another commonly used hydrogel system is based on copolymers of vinyl 
pyrrolidone and methyl methacrylate. The equilibrium water content of 
these hydrogels can vary widely as a function of the ratio of vinyl 
pyrrolidone to methyl methacrylate. However, most hydrogels of commercial 
interest have a water content in the 70% to 80% by weight range. These 
hydrogels are often referred to as high water content hydrogels. 
As a general rule the low water content hydrogels have acceptable 
mechanical properties for application as a soft contact lens. However, 
they do not have acceptable oxygen permeability (DK) to be used as an 
extended wear contact lens. Also, as a general rule the high water content 
hydrogels appear to have acceptable oxygen permeability for application as 
an extended wear contact lens but have poor mechanical properties, i.e., 
are not easily formed into stable lenses, are tearable, sometimes lack 
visual acuity, and are easily damaged. 
For many other biomedical applications it is also apparent that the utility 
of hydrogels have been limited by a lack of suitable mechanical 
properties. Accordingly, there is a real and continuing need to develop 
hydrogels which have improved mechanical properties and maintain the other 
desirable features of hydrogels such as biocompatibility, softness, 
transparency, and permeability to oxygen and other metabolites. The 
primary object of this invention is to fill this need. 
It is a more specific objective of the present invention to prepare 
hydrogel type contact lenses of improved mechanical properties which have 
good optical properties and acceptable oxygen permeability. This objective 
is achieved by the copolymerization of a hydrogel forming monomer (or 
monomers) and a hydroxyfluoro alkylstyrene, preferably 
p-(2-hydroxyhexafluoroisopropyl) styrene (HFIS). 
SUMMARY OF THE INYENTION 
According to the present invention there is provided a hydrogel of a 
copolymer of a hydrophilic monomer (or monomers) and a 
hydroxyfluoroalkylstyrene, the most preferred being HFIS. 
For the most part the remaining description is given with reference to 
HFIS, but it is to be understood this is for brevity and that unless 
othewise stated, or specifically referring to HFIS as the preferred 
embodiment, other hydrofluoroalkylstyrenes may be employed in lieu of 
HFIS. 
Similarly, in the remaining description, reference is made to HEMA 
hydrogels, but it is to be understood this is for brevity and that unless 
otherwise stated, or specifically referring to HEMA hydrogels, other 
hydrophilic monomers may be employed in lieu of HEMA.

DETAILED DESCRIPTION OF THE INVENTION 
Polymer hydrogels are widely used for biomedical applications such as 
contact lenses and a large number of hydrogels of this type are based on 
the polymers described in U.S. Pat. No. 3,220,960 (Wichterle et al), whose 
disclosure as it relates to hydrogel monomers is incorporated herein by 
reference. Wichterle's polymers are hydroxy (lower alkyl C.sub.1 to 
C.sub.8) methacrylates or acrylates, cross-linked with a small percentage 
of the corresponding diester, e.g., ethylene glycol dimethacrylate 
(EGDMA). Polymers based upon hydroxyethyl methacrylate (HEMA) and 
cross-linked with EGDMA can be hydrated to form clear hydrogels having 
good mechanical properties. 
As earlier mentioned, a degree of cross-linking in a copolymer is necessary 
to form a three dimensional polymer network structure. Typically one uses 
about 0.2% by weight of the composition to about 5% by weight of the 
composition of cross-linking comonomer. Yarious cross-linking comonomers 
may be employed such as glycol diacrylates, glycol dimethacrylates, like 
EGDMA including ethylene and propylene glycol diacrylates and 
dimethacrylates, polyethylene glycol diacrylates and dimethacrylates, 
allyl methacrylates, etc. 
According to one aspect of the present invention there is provided a 
hydrogel which comprises a copolymer of a hydroxy lower (C.sub.1 to 
C.sub.8) alkyl methacrylate or acrylate with HFIS, the amount of hydroxy 
lower alkyl methacrylate or acrylate being from about 40% to about 95%, 
and the amount of HFIS being from 5% to 60% of the total polymer 
composition, preferably the hydroxy lower alkyl methacrylate, or acrylate 
is from about 70% to about 90% and the HFIS from 10% to 30% of the total 
polymer composition. These percentages are on a total polymer weight basis 
and exclude added water. 
The copolymerizeable hydroxy lower alkyl (C.sub.1 to C.sub.8) methacrylate 
or acrylate need not be described herein in detail, such hydrogel forming 
monomers being well-known and described previously in the earlier 
incorporated-by-reference Wichterle U.S. Pat. No. 3,220,960. As those 
skilled in the art know, the hydrogel monomer may also contain other 
comonomers such as vinyl pyrrolidone. The amount of the hydrogel monomer 
has previously been specified. 
With regard to the amount of copolymerizable hydroxyfluoroalkylstyrene, 
such as p-(2-hydroxyhexafluoroisopropyl) styrene (HFIS), again, the amount 
on a weight basis of the total copolymer, exclusive of the added water has 
been previously specified, i.e. from about 10% by weight to about 30% by 
weight on a preferred basis and in a broader aspect from about 5% to about 
60% by weight of the total polymer composition. 
In accordance with this invention an hydroxyfluoroalkylstyrene, such as 
HFIS, or chemically p-(2-hydroxyhexafluoroisopropyl) styrene may be added 
as a comonomer to the other more conventional hydrogel monomer 
compositions to prepare a hydrogel of improved mechanical properties. As 
earlier mentioned, other hydroxyfluoroalkylstyrenes besides HFIS, 
generally of the type disclosed in U.S. Pat. No. 3,179,640 can be used 
herein. The disclosure of U.S. Pat. No. 3,179,640, patented Apr. 20, 1965, 
to the extent of its general description of hydroxyfluoroalkylstyrene 
monomers, their formulas and their method of preparation is specifically 
incorporated herein by reference. The hydroxyfluoroalkylstyrenes shown in 
that patent may have the following general formula: 
##STR1## 
wherein X and Y are, individually, the same or different monovalent 
fluoroalkyl, including perfluoroalkyl, .omega.-hydroperfluoroalkyl and 
.omega.-chloroperfluoroalkyl, radicals, or jointly, a divalent 
perfluoroalkylene radical. Preferable for this invention X and Y are 
C.sub.1 to C.sub.8 alkyl, and most preferred C.sub.1 to C.sub.3 alkyl. 
There is no disclosure of any utility of HFIS monomers in the 
incorporated-by-reference U.S. Pat. No. 3,179,640 as useful in polymeric 
compositions for biomedical devices, in particular, as monomers or 
comonomers for use in preparation of ophthalmic lenses, and in particular 
contact lenses. 
The monomer, p-(2-hydroxyhexafluoroisopropyl) styrene (HFIS) has merely 
been described in U.S. Pat. No. 3,179,640 as yielding polymers and 
copolymers having unusual swelling characteristics and solvent resistance 
properties. Uses there mentioned include the use of such polymers and 
copolymers as coatings, molded articles and clarifying agents in 
solvent-cast polyamide films. There is also mention in the literature, as 
exemplified by the article by Pearce et al, Journal of Macromolecular 
Science-Chemistry, A21, 1181-1216 (1984), of the use of HFIS as a 
comonomer to effect polymer compatibilization through hydrogen bonding. 
Thus, the monomer per se has been known in the literature for many years. 
However, the ability of HFIS to form hydrogels and more specifically 
hydrogels of exceptional mechanical properties has not been considered nor 
has the use of such copolymers as biomedical devices and specifically 
biomedical devices for ophthalmic applications ever been suggested. It is 
the combination to which the present invention is directed. 
The preferred HFIS monomer has the formula: 
##STR2## 
The following properties of HFIS make it the most preferred 
hydroxyfluoroalkylstyrene compound for use in hydrogel forming copolymers 
intended for biomedical applications, and specifically for ophthalmic 
applications, in accordance with this invention. The pKa of HFIS is 
.about.5.5 compared to the .about.4.8 found with acrylic acid type 
comonomers. The index of refraction (n.sub.D.sup.25) of HFIS is 1.4577 
compared to 1.4290 for methacrylic acid. The oxygen permeability (DK) of 
the homopolymer is 2.3.times.10.sup.-11 ; and the presence of the fluorine 
substituents may significantly reduce interaction with biological fluids 
such as tears. 
The properties of hydrogels containing HFIS are unique and unexpected. 
There have been many attempts in the prior art to improve the mechanical 
properties of hydrogels. However, these have been restricted to specific 
systems and are not based on the use of a comonomer that can improve the 
mechanical properties of hydrogels via incorporation by a copolymerization 
mechanism. Thus for example, Ofstead in U.S. Pat. No. 4,528,325 claims 
hydrogels of high strength based on the solvolysis of copolymers of vinyl 
trifluoroacetate (VTA) and up to 5% of certain comonomers such as vinyl 
esters or disubstituted ethylene monomers. These copolymers appear to have 
improved mechanical properties, however, unlike the HFIS copolymers they 
require the extra step of a reaction on a polymer and of course are very 
limited in compositions as they require the presence of at least 95% vinyl 
trifluoroacetate. 
Another attempt at preparing high strength hydrogels is that of Stoy et al, 
is exemplified by U.S. Pat. No. 4,095,877. In this technique polymers or 
copolymers containing acrylonitrile are hydrolyzed to form high strength 
hydrogels. This technique also requires a reaction on a polymer and is far 
more limited in its scope than the present use of HFIS to improve the 
strength of hydrogels of varying compositions. Thus it can be seen that 
the copolymers of the present invention have distinct advantages. In 
short, while there are numerous reported attempts to improve mechanical 
properties that involve very specific hydrogel systems or a very narrow 
range of compositions, see e.g. U.S. Pat. Nos. 4,492,776, 4,451,630, 
4,440,919, 4,436,887, and 4,433,111, none of these patents describe 
systems that have the wide applicability or range of mechanical properties 
that are found with hydrogels based on copolymers incorporating HFIS. It 
can thus be seen that the present hydrogels not only may improve 
mechanical properties but also are advantageous in the wide range of 
hydrogels that can be prepared. 
With regard to the portion of the copolymer which comprises the hydrogel, 
it should be understood that it may comprise not only the hydroxy lower 
C.sub.1 to C.sub.8 alkyl methacrylate or acrylate, but that other 
hydrophilic monomers may be part of the 40% to 95%, or the preferred 70% 
to 90%. Those other hydrophilic monomers are known, often used in making 
hydrogel type soft lenses, and described in the earlier mentioned hydrogel 
patents. 
Examples of another class of useable and suitable hydrophilic monomers are 
the N-vinyl heterocyclic monomers, suitable examples of such monomers 
being N-vinyl-2-pyrrolidone, N-vinyl pyridine and 
N-vinyl-.epsilon.-caprolactam. Also another class of hydrophilic monomers 
are the polymerizable olefinic acids and amides; suitable examples being 
acrylic acid, methacrylic acid, itaconic acid, fumaric acid, maleic acid, 
crotonic acid, acrylamide, methacrylimide and N-(1,1-dimethyl-3-oxabutyl 
acrylamide). Another suitable group of hydrophilic monomers are the lower 
alkyl vinyl ethers such as methyl and ethyl vinyl ether. 
As heretofore mentioned, certain ranges of cross-linking monomers 0.1% to 
5% may also be employed. These may be used to harden the resulting 
copolymer or to improve machineability or stability, or both. Examples of 
suitable cross-linking monomers are divinyl benzene, di- and higher 
functionality methacrylates and acrylates such as ethylene glycol 
dimethacrylate, tetraethylene glycol dimethacrylate, polyethylene glycol 
dimethacrylate, trimethylol propane trimethylacrylate, pentaerythritol 
tetramethacrylate, and allyl methacrylate, allyl itaconate, diallyl 
itaconate, diallyl adipate and methylenebisacrylamide. The foregoing 
examples of cross-linking monomers are merely illustrative, other known 
polymer cross-linkers may also be used, and all may be used individually, 
or in combination. 
In addition to each of the above described amounts of hydrophilic monomer, 
and cross-linking agent, one may optionally include from 0% to 40% of a 
hydrophobic monomer such as methyl methacrylate, cyclohexyl methacrylate, 
styrene, tertiary butyl styrene, etc. The hydrophobic monomers which will 
modify the mechanical properties and other hydrophobic monomers mentioned 
in the previously referred to parent application may also be employed. 
The following examples are offered to further illustrate, but not 
necessarily limit the process and composition of the present invention. 
EXAMPLE 
Films of the composition as shown in Table I below were prepared between 
(4.times.4 in.) glass plates. The glass plates were pretreated with 
dimethyldichlorosilane and hydrolyzed to silanize the surface. Masking 
tape was placed around the edges of a glass plate to control the film 
thickness (target thickness was usually 0.1 mm). The monomer mix was 
placed on a glass plate, the two plates secured together by means of a 
metal clip and the assembly placed in an oven at 50.degree. C. for one and 
one half hour. At the end of this time the glass plate assembly was heated 
to 90.degree. C. for an additional 90 minutes. The thin film was then 
removed from the glass plate assembly and stored in distilled water 
(phosphate buffer, pH 7.4). For all of the copolymers listed in Table I, 
1.0 weight % of USP 245 (2,5-dimethyl-2,5-diperoxyl-2'-ethylhexoate 
hexane) was added. 
Oxygen permeability (DK) was measured in a water/water cell using an 
O.sub.2 Permeometer.TM.Model 101T. The units of DK are cm.sup.2 /sec 
(mlO.sub.2 /ml mmHg).times.10.sup.-11. Mechanical properties were measured 
using an Instron.TM. universal testing instrument, Model 1122. Tests were 
carried out with the test specimen in a water bath. The units of tensile 
strength and modulus are Kg/cm.sup.2. 
TABLE I 
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A B C 
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HEMA 100 90 80 
HFIS -- 10 20 
H.sub.2 O Content (%) 
35 27 20 
DK 9.8 5.1 2.7 
Tensile Strength 
9.0 -- 70 
Modulus 11 -- 1,200 
% Elongation 140 -- 200 
Index of Refraction 
1.438 1.457 1.472 
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The oxygen permeability of the HFIS copolymers was not as high as expected. 
The decrease is ascribed to the decrease in water content. However, there 
was a dramatic increase in physical properties, far beyond that which 
would necessarily be expected. Moreover, the index of refraction of the 
copolymer gels was higher than expected based only on reduced water 
content, i.e. 1.472 compared to 1.466 (calculated). The evidence shows 
that excellent hydrogel compositions useful for contact lenses can be 
prepared. 
When the above examples are repeated with hydroxy perfluoro C.sub.1 to 
C.sub.8 alkyl sytrenes, at similar levels of addition, substantially 
similar results can be obtained in that good hydrogel materials are 
obtained having improved mechanical properties. These materials may be 
used to formulate hydrogel type soft contact lenses having the same 
properties as demonstrated by the polymer films.