UV curable crosslinking agents useful in copolymerization

A novel class of compounds are disclosed which may be used as novel crosslinking agents for acrylic-containing, vinyl-containing and/or styrene-containing hydrophilic monomers to prepare novel UV-curable hydrophilic copolymers suitable for use as biomedical articles, especially contact lenses.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to a novel class of compounds which may be used as 
novel crosslinking agents to prepare novel UV-curable hydrophilic 
copolymers suitable for use as articles in the biomedical field, 
especially contact lenses. 
2. Background 
In the field of crosslinked polymeric systems, initiators, and crosslinking 
compounds and compositions (crosslinkers) are often added to monomer mixes 
before polymerization. These crosslinkers facilitate formation of the 
desired polymer. In addition, crosslinkers can affect specific 
characteristics and mechanical properties of the resultant polymers. 
Crosslinkers which are similar in structure to the monomers being reacted 
are often added to monomer mixtures. For example, a di(meth)acrylate or 
di(meth)acrylamide monomer would commonly be used as a crosslinker for a 
(meth)acrylate/(meth)acrylamide system. Alternatively, to react a 
vinyl-type system comprising N-vinyl pyrrolidone or vinyl acetate, for 
example, a vinyl-type crosslinker such as allyl methacrylate would 
ordinarily be used. For the purposes of this application, the terms, 
"vinyl-type" or "vinyl-containing" refer to those non-acrylic monomers 
having the vinyl grouping (CH.sub.2 .dbd.CH--), and which are generally 
reactive. "Acrylic-type" or "acrylic-containing" monomers refer to those 
monomers containing the acrylic grouping (CH.sub.2 .dbd.CRCOX--). 
When a specific copolymeric system is desired which includes both a 
methacrylate-containing monomer and a non-acrylic vinyl-containing 
monomer, polymerization problems occur as a result of the varying 
reactivity of the two monomer types. In other words, non-acrylic 
vinyl-containing monomers are generally not reactive with the 
(meth)acrylate-containing monomers. 
Therefore, to copolymerize N-vinyl pyrrolidone (NVP) with, for example, 
methyl methacrylate (MMA), allyl methacrylate has been used as a 
crosslinker with t-butylperoxyoctoate added as a thermal reaction 
initiator, and benzoin methyl ether (BME) as a photoinitiator. Such a 
monomer mix may then be first subjected to UV irradiation to polymerize 
the methacrylate groups, followed by heat curing to polymerize the allyl- 
and vinyl-containing monomers. This polymerization scheme is relatively 
cumbersome and may lead to polymeric systems having poor yields or a 
resulting polymer of poor optical quality. In addition, such resulting 
polymers may not be true crosslinked copolymers but may be mere 
nonhomogeneous interpenetrating polymer networks. 
Alternately, a crosslinker such as allyl methacrylate could be used to 
assist the polymerization of the NvP/methacrylate system; however, this 
would also require heat curing. Heat curing is not as desirable as UV 
curing since over-heating may adversely affect the desired properties of 
the end-product hydrogel. In addition, insufficient heat curing can result 
in a hydrogel which also fails to possess the desired end-result 
properties. 
Other known crosslinking agents often used in polymeric syntheses are 
polyvinyl, typically di- or tri-vinyl monomers, most commonly the di- or 
tri(meth)acrylates of dihydric ethylene glycol, triethylene glycol, 
butylene glycol, hexane-1,6-diol, thio-diethylene glycol-diacrylate and 
methacrylate; neopentyl glycol diacrylate; trimethylolpropane triacrylate 
and the like; N,N,-dihydroxyethylene-bisacrylamide and 
-bismethacrylamides; also diallyl compounds like diallyl phthalate and 
triallyl cyanurate; divinylbenzene; ethylene glycol divinyl ether; and the 
(meth)acrylate esters of polyols such as triethanolamine, glycerol, 
pentanerythritol, butylene glycol, mannitol, and sorbitol. Further, 
illustrations include N,N-methylene-bis-(meth)acrylamide, sulfonated 
divinylbenzene, and divinylsulfone. Also useful are the reaction products 
of hydroxyalkyl (meth)acrylates with unsaturated isocyanates, for example 
the reaction product of 2-hydroxyethyl methacrylate with 2-isocyanatoethyl 
methacrylate (IEM) as disclosed in U.S. Pat. No. 4,954,587. 
Other known crosslinking agents are the 
polyether-bisurethane-dimethacrylates as described in U.S. Pat. No. 
4,192,827, and those crosslinkers obtained by reaction of polyethylene 
glycol, polypropylene glycol and polytetramethylene glycol with 
2-isocyanatoethyl methacrylate (IEM) or 
m-isopropenyl-.gamma.,.gamma.-dimethylbenzyl isocyanates (m-TMI), and 
polysiloxane-bisurethane-dimethacrylates as described in U.S. Pat. Nos. 
4,486,577 and 4,605,712. Still other known crosslinking agents are the 
reaction products of polyvinyl alcohol, ethoxylated polyvinyl alcohol or 
of polyvinyl alcohol-co-ethylene with 0.1 to 10 mol % vinyl isocyanates 
like IEM or m-TMI. However, none of the above-mentioned crosslinkers can 
be used to copolymerize vinyl and acrylic comonomers using only UV curing. 
It is also known that NVP copolymerizes well with vinyl carbonates and 
vinyl carbamates. Specifically, NVP was shown to copolymerize with 
vinylene carbonate. The closeness of the reactivity ratios resulted in 
favorable random copolymerization. (See K. Hayashi and G. Smets, J. 
Polymer Science, Vol. 27, p. 275, (1958)). Further, it has been recently 
demonstrated that NVP can copolymerize with vinyl carbamates and 
carbonates with a UV sensitive initiator. (See U.S. Pat. No. 5,070,215). 
It was discovered in the field that certain crosslinked polymeric materials 
could be hydrated and retain their water content. It was further found 
that the higher the water content within contact lenses made from these 
crosslinked hydrogel polymers, the greater was the oxygen permeability 
through the lens to the cornea. 
In the field of contact lenses, various factors combine to yield a material 
that has appropriate characteristics. Oxygen permeability, wettability, 
material strength and stability are but a few of the factors which must be 
carefully balanced to achieve a useable end-result contact lens. 
Generally, as the water content of a hydrogel increases, oxygen 
permeability also increases. Since the cornea receives its oxygen supply 
exclusively from contact with the atmosphere, good oxygen permeability is 
a critical characteristic for any contact lens material. 
In the case of hydrogel preparation, the crosslinkers affect specific 
mechanical properties relating to the firmness of the hydrogel, such as 
modulus, and tear strength. As a result, it is desirable in the field of 
hydrogel synthesis to introduce specific crosslinkers to copolymerize in a 
predictable way with the comonomers in the monomer mix, thereby creating 
hydrogels having certain desired properties. 
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 biocompatibilty. 
As a result there has been extensive interest in the use of hydrogels for 
various biomedical applications as biomedical devices. For example, 
hydrogels can be used as contact lenses, intraocular implants, membranes 
and other films, diaphragms, catheters, mouth guards, denture liners, 
tissue replacements, heart valves, intrauterine devices, ureter 
prostheses, etc. Commercial success for hydrogels has been found in the 
field of ophthamology, most particularly as contact lenses. 
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. Particularly, 
poly(2-hydroxyethyl methacrylate), also known as poly-HEMA, was disclosed 
as an illustrative hydrogel having a water content of about 39% by weight. 
Hydrogels such as 2-hydroxyethyl methacrylate with water contents of about 
40% by weight, are often referred to as low water content hydrogels. 
Another known hydrogel system is comprised of copolymers of N-vinyl 
pyrrolidone (NVP) and a methacrylate, such as methyl methacrylate (MMA). 
The water content of the NVP-MMA hydrogel systems can vary widely as a 
function of the ratio of NVP to MMA. However, most hydrogels derived from 
NVP and MMA which are of commercial interest have a water content in the 
70% to 80% by weight range. Hydrogels containing N,N-dimethylacrylamide 
copolymers (DMA) are known to have similar properties. Hydrogels 
containing water weight percents in this range are often referred to as 
high water content hydrogels. 
High water-containing hydrogels have at times exhibited undesirable 
mechanical properties. For example, such hydrogels are not easily formed 
into hydrolytically stable lenses. Further such materials have at times 
exhibited tearing or other breakage as a result of poor tensile strength. 
What was needed was a highly oxygen permeable material that was durable 
and highly wettable. Wettability is important in that if the lens is not 
sufficiently wettable, it does not remain lubricated and therefore cannot 
be worn comfortably on the eye. The optimal contact lens would have not 
only excellent oxygen permeability, but also excellent tear fluid 
wettability. 
As a general rule, low water content hydrogels have acceptable properties 
for application as soft contact lenses. High water content hydrogels 
appear to have acceptable oxygen permeability suitable for use as extended 
wear lenses. Extended wear lenses are those worn without removal for 
periods of time longer than a day. However, high water content hydrogels 
are often not easily formed into stable lenses. Such high water-containing 
lenses have been reported to tear more easily, and may otherwise be more 
prone to damage. 
Theoretically, the most desirable lens would have oxygen transmissibility 
at least as high as that of lenses comprising the NVP-MMA system, while 
also having strength and mechanical properties similar to lenses made from 
the poly-HEMA hydrogels. 
Silicone-containing materials were tried as viable contact lens materials 
and displayed very good oxygen permeability and durability. However, most 
silicone-containing materials are largely hydrophobic and therefore not 
sufficiently wettable. Further, it is believed that such hydrophobicity 
causes deposit problems, which may result in discomfort when wearing 
contact lenses made from these silicone-containing polymers. The optimum 
contact lens would have not only excellent oxygen permeability, but also 
excellent tear-fluid wettability. 
As mentioned previously, curing hydrogels solely with UV radiation would be 
preferable to heat curing. However, no completely UV curable 
acrylic/vinyl- or styrene/vinyl-or acrylic/vinyl/styrene-crosslinked 
polymeric system, is presently known. Such a UV-curable polymeric hydrogel 
system employing a crosslinker able to compatibilize groups of varying 
reactivities would be highly advantageous. 
SUMMARY OF THE INVENTION 
In accordance with this invention novel crosslinking agents for UV-curable 
polymeric hydrogel systems are disclosed which comprise at least one 
vinyl-containing monomer and at least one of either a styrene-containing 
or an acrylic-containing monomer. The novel crosslinkers are able to 
polymerize hydrogel systems which contain in the monomer mix, both, at 
least one vinyl, and at least one of either a styrene or an acrylic group. 
The resulting, entirely UV-curable hydrogels derived from the monomeric 
mix therefore comprise at least one vinyl-containing monomer, at least one 
acrylic- or styrene-containing monomer, and a crosslinking agent derived 
from a novel class of crosslinkers. Alternatively, the monomeric mix may 
comprise at least one vinyl-, at least one acrylic- and at least one 
styrene-containing monomer and the novel crosslinker. 
These novel crosslinkers have the schematic representation (I): 
##STR1## 
wherein 
V denotes a vinyl-containing group having the formula: 
##STR2## 
A' denotes an acrylic-containing group having the formula: 
##STR3## 
S denotes a styrene-containing group having the formula: 
##STR4## 
wherein 
R.sub.1, is an alkyl radical derived from substituted and unsubstituted 
hydrocarbons, polyalkylene oxide, poly(perfluoro) alkylene oxide, 
dialkyl-capped polydimethylsiloxane, dialkyl-capped polydimethylsiloxane 
modified with fluoroalkyl or fluoroether groups; 
R.sub.2' -R.sub.10' are independently H, or alkyl of 1 to 5 carbon atoms; 
Q is an organic group containing aromatic moieties having 6-30 carbon 
atoms; X, Y, and Z are independently 0, NH or S; v' is I, or higher; and 
a', s' are independently greater than or equal to 0, and a'+s' is greater 
than or equal to 1. 
These new crosslinking compounds, useful as new polymeric crosslinking 
agents are suitable for use in the preparation of new hydrogel polymers 
which, in turn, may be used in the preparation of a wide range of various 
biomedical devices, such as, contact lenses, surgical devices, heart 
valves, vessel substitutes, intrauterine devices, membranes and other 
films, diaphragms, catheters, mouth guards, denture liners, and 
intraocular devices. The resulting new hydrogels are especially 
well-suited for the production of contact lenses.

DETAILED DESCRIPTION OF THE INVENTION 
The present invention is directed to new crosslinking agents which link 
monomers and prepolymers to form new copolymers which are particularly 
useful as biomedical materials, and are especially useful in contact lens 
applications. These new crosslinking agents can be used with a wide 
variety of monomers and prepolymers and can produce a wide variety of 
contact lens materials such as, for example, hard gas permeable lens 
materials; soft hydrogen lens materials, soft non-hydrogel lens materials, 
silicone-containing polymeric materials and non-silicone-containing 
polymeric materials. 
The novel crosslinkers of the present invention can be prepared by 
employing known organic reaction syntheses to combine the acrylic or 
styrene group from acrylic-containing or styrene-containing monomers 
respectively with the vinyl group from the vinyl-containing monomers, such 
as the preferred vinyl carbonates or vinyl carbamates. 
The crosslinkers can be prepared by means of a condensation reaction of an 
alcohol or an amine which contains an acrylic or styrene group, with, for 
example vinyl chloroformate under mild reaction conditions (e.g. at 
ambient temperature or below). The crosslinkers can also be prepared by an 
addition reaction of the same type of alcohol or amine mentioned above, 
with vinyl isocyanate at lower temperatures (at or below 10 degrees C.). 
Both types of reactions are further depicted by the following reaction 
schemes: 
##STR5## 
wherein 
R is a residue containing an acrylic or a styrene-containing group, or 
both; and X is NH, O or S. 
One preferred example for such a condensation reaction is the reaction of 
2-hydroxyethyl methacrylate (HEMA) with vinyl chloroformate to yield 
methacryloxyethyl vinyl carbonate (HEMAVc). One preferred example of an 
addition reaction used to produce a novel crosslinker is the reaction of 
HEMA with vinyl isocyanate to form methacryloxyethyl vinyl carbamate. 
A crosslinker having a styrene and vinyl group such as 4-vinylphenyl vinyl 
carbonate can be produced by reacting 4-vinyl phenol (CTC Organics, 
Atlanta Ga. and Polysciences, Philadelphia, Pa.), with vinyl chloroformate 
under mild condensation reaction conditions. Another preferred 
crosslinker, 4-vinylphenyl carbamate can be prepared in an addition 
reaction by reacting 4-vinyl phenol with vinyl isocyanate. Alternately, a 
crosslinker containing a styrene and vinyl group can be prepared by 
reacting p-chloromethylstyrene (Dow Chemical) with a vinyl 
carbamate-containing acid under mild reaction conditions, and using 
1,8-diazabicyclo[5,4,0]-7-undecene as an acid receptor. 
Crosslinkers containing a urea group can be prepared by reacting an 
ammonium salt containing a styrene or methacrylate moiety, such as 
2-aminoethyl methacrylate hydrochloride (Kodak) with vinyl isocyanate 
under basic conditions at ambient temperature or below. 
Vinyl isocyanate, the intermediate useful for making vinyl urea and vinyl 
carbamate, can be prepared by reacting acrylyl chloride with sodium azide 
at 10 degrees C or below, followed by distillation of the product into a 
cold trap containing an inhibitor such as hydroquinone. (See G. B. Butler 
and S. B. Monroe, J. Macro. Sci., A5(6), 1063-1070 (1971)). 
While the present invention can be used with many polymeric materials 
including hydrogels, especially preferred are hydrogels, the specific 
polymers of which may be derived from monomers which may include acrylate, 
acrylamide, methacrylate, methacrylamide, styrene-containing monomers, 
dimethacrylate and dimethacrylamide monomers, vinyl amide-containing 
monomers, vinyl carbonate/carbamate/urea monomers, and 
(meth)acrylate/(meth) acrylamide-capped prepolymers All of the 
above-mentioned monomers and prepolymers may further include 
polysiloxanes, polyfluorosiloxanes, polyfluoroethers, polyurethanes, and 
other groups. 
One preferred class of suitable silicone-containing monomers contemplated 
by the present invention are bulky polysiloxanylalkyl (meth)acrylic 
monomers represented by the formula (II): 
##STR6## 
wherein: 
X is O or NR; 
each R is independently hydrogen or methyl; and 
each R.sup.1 is independently a lower alkyl or phenyl group; and 
f is 1 or 3 to 10. 
Examples of such bulky monomers include methacryloxypropyl 
tris(trimethylsiloxy)silane, pentamethyldisiloxanylmethylmethacrylate, 
tris(trimethylsiloxy)methacryloxy propylsilane, 
phenyltetramethyldisiloxanylethyl acetate, and 
methyldi(trimethylsiloxy)methacryloxymethyl silane. 
A further preferred class of silicone-containing prepolymers is a 
poly(organosiloxane) prepolymer represented by the formula (III): 
##STR7## 
wherein: 
A is an activated unsaturated group, such as an ester or amide of an 
acrylic or a methacrylic acid; 
each R.sup.3 -R.sup.6 is independently selected from the group consisting 
of a monovalent hydrocarbon radical or a halogen substituted monovalent 
hydrocarbon radical having 1 to 18 carbon atoms which may have ether 
linkages between carbon atoms; 
R.sup.7 is a divalent hydrocarbon radical having from 1 to 22 carbon atoms; 
and 
n is 0 or an integer greater than or equal to 1. 
Another preferred class of silicone containing monomers includes 
silicone-containing vinyl carbonate or vinyl carbamate monomers of formula 
(IV): 
##STR8## 
wherein: 
Y' denotes --O--, --S--or --NH--; 
R.sup.Si denotes a silicone-containing organic radical; 
R.sup.8 denotes hydrogen or methyl; 
d is 1, 2, 3 or 4; and q is 0 or 1. 
Suitable silicone-containing organic radicals R.sup.Si include radicals 
having any of the following formula: 
##STR9## 
wherein: 
R.sup.10 denotes 
##STR10## 
wherein 
p' is 1 to 6; 
R.sup.11 denotes an alkyl radical or a fluoroalkyl radical with 1 to 6 
carbon atoms; e is 1 to 200; n, is 1, 2, 3 or 4; and m, is 0, 1, 2, 3, 4 
or 5. 
The silicone-containing vinyl carbonate or vinyl carbamate monomers 
specifically include: 
1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane; 
3-(trimethylsilyl)propyl vinyl carbonate; 
3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane]; 
3-[tris(trimethylsiloxy)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 "V.sub.2 D.sub.25 ", represented by the following formula 
(V): 
##STR11## 
A further preferred class of silicone-containing prepolymers are those 
monomers having the following schematic representations: 
##STR12## 
wherein 
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; 
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; 
* denotes a urethane or ureido linkage; 
a is at least 1; 
A" denotes a divalent polymeric radical of formula (VIII): 
##STR13## 
wherein: 
R.sup.2 and R.sup.2' independently denote an alkyl or fluoro-substituted 
alkyl group having 1 to 10 carbon atoms which may contain ether linkages 
between carbon 
m is at least 1; and 
p provides a moiety weight of 400 to 10,000; 
E and E' independently denote a polymerizable unsaturated organic radical 
represented by formula (IX): 
##STR14## 
wherein: 
R.sup.14 denotes a divalent alkylene radical having 1 to 10 carbon atoms; 
R.sup.12 denotes H or CH.sub.3 ; 
R.sup.13 denotes H, a (C.sub.1 -C.sub.6) alkyl radical or a 
--CO--Y--R.sup.15 group wherein Y is --O--, --S--or --NH--and R.sup.15 is 
a alkyl radical having 1 to 12 carbon atoms; 
X is --CO--or --OCO--; 
Z is --O--or --NH--; 
Ar denotes an aromatic radical having 6 to 30 carbon atoms; 
w is 0 to 6; 
x is 0 or 1; 
y is 0 or 1; and 
z is 0 or 1. 
Most preferred are the silicone-containing hydrogel contact lenses made 
from polyurethane hydrogel compositions comprising a urethane prepolymer, 
a polysiloxanylalkyl methacrylate, at least one acrylic-containing 
monomer, a vinyl-containing monomer, and the crosslinker of the present 
invention. The urethane prepolymer is a methacrylate-based prepolymer of 
the general formula (X): 
##STR15## 
wherein: 
R.sup.16 is a diradical of a diisocyanate after removal of the isocyanate 
group, and is most preferably the diradical of isophorone diisocyanate, 
and m, p and a are the same as previously defined. Preferably, the sum of 
m and a is 3 or 4, and more preferably, a is 1 and m is 3 or 4. 
Preferably, p is at least 30. 
Monomer systems for hydrogel lenses often employ a hydrophilic monoolefinic 
monomer (i.e., a monoethylenically unsaturated monomer) and a polyolefinic 
(usually diolefinic) monomer (e.g., a polyethylenically unsaturated 
compound which functions as a crosslinking agent) in an amount sufficient 
to insolubilize the resulting hydrophilic hydrogel but insufficient to 
completely mask the hydrophobic properties of the hydrogel. Mixtures of 
hydrophilic monoolefinic monomers are also used to adjust various 
properties of the polymeric material, as is well known in the art. 
Illustrative hydrophilic monomers include, for example, water soluble 
monoesters of (meth)acrylic acid with an alcohol having an esterifiable 
hydroxyl group and at least one additional hydroxyl group such as the 
mono- and poly-alkylene glycol monoesters of (meth)acrylic acid, e.g., 
ethylene glycol mono(meth)acrylate, diethylene glycol mono(meth)acrylate, 
propylene glycol mono(meth)acrylate, dipropylene glycol 
mono(meth)acrylate, and the like; the N-alkyl and N,N-dialkyl substituted 
(meth)acrylamides such as N-methyl (meth)acrylamide, N,N-dimethyl 
(meth)acrylamide, and the like; N-vinylpyrrolidone and the alkyl 
substituted N-vinyl pyrrolidones; N-vinyl-N-alkyl amides such as 
N-vinyl-N-methyl acetamide, N-vinyl-N-methyl-formide, N-vinyl acetamide, 
N-vinyl formamide; glycidyl (meth)acrylates; the unsaturated amines; the 
alkoxy ethyl acrylates; fumarates, mixtures thereof; and others known to 
the art. 
Contemplated preferred acrylic-containing monomers identified in Formula I 
as "Aa'", and which in part comprise the novel crosslinking composition of 
the present invention, include the (meth)acrylates, (meth)acrylamides, 
alkyl(meth)acrylates, alkyl(meth)acrylamides, 
polysiloxyalkyl(meth)acrylates, polysiloxyalkyl(meth)acrylamides, 
fluoroalkyl(meth)acrylates, fluoroalkyl(meth)acrylamides, with the more 
preferred monomers being 2-hydroxyethylmethacrylate, glycerol 
methacrylate, hydroxyethyl methacrylamide, 2-methacrylamido ethanol, 
N,N-dimethyl acrylamide, N,N-dimethyl methylacrylamide, (meth)acrylic acid 
and derivatives thereof. The acrylic-containing monomers may further be a 
prepolymer end-capped with (meth)acrylate- or (meth)acrylamide-containing 
monomers, with the preferred prepolymers being polysiloxane-, polyalkylene 
ether-, or polyfluorinated ether-containing monomers and derivatives 
thereof, all of which may be linked through ester, carbonate, carbamate, 
urea or urethane linkages. The polysiloxane units in 
polysiloxane-containing prepolymers may further contain fluoroalkyl, 
fluoroether, alkyl ether or alcohol groups and derivatives thereof. 
The contemplated preferred vinyl-containing monomers present in the novel 
crosslinker and identified in Formula I as "V.sub.v ", may include, vinyl 
carbonate, alkyl vinyl carbonate, polysiloxane vinyl carbonate, 
fluoroalkyl vinyl carbonate, polysiloxanylalkyl-vinyl carbonate, 
fluoroalkyl vinyl carbonate monomers, and the corresponding carbamate and 
urea monomers such as vinyl urea, alkyl vinyl urea, polysiloxanylalkyl 
vinyl urea and fluoroalkyl vinyl urea monomers. The more preferred 
vinyl-containing monomers include N-vinylpyrrolidone, N-vinyl,N-methyl 
acetamide, N-vinyl,N-methyl formamide, N-vinyl acetamide, N-vinyl 
formamide, and 2-vinyl-4,4-dimethyl-2-oxazoline-5-one (VDMO) and 
derivatives thereof. 
In addition, the vinyl-containing monomer may be a prepolymer selected from 
vinyl carbonate-, vinyl carbamate-, and vinyl urea-capped prepolymers and 
may further comprise polysiloxanes, fluoroalkyl- or fluoroether-containing 
monomers, and more preferably may include a polyalkylene ether or 
polyfluorinated ether all of which may be linked through ester, carbonate, 
carbamate, urea or urethane linkages. The preferred 
polysiloxane-containing vinyl prepolymers may include an alkyl ether or an 
alcohol. 
The contemplated preferred styrene-containing monomers present in the novel 
crosslinker and identified in Formula I as "S.sub.s ", may include 
4-vinylphenyl vinyl carbonate, 4-vinylphenylvinyl carbamate, or 
4-vinylphenylvinyl urea and derivatives thereof. Further, the crosslinking 
agent may comprise all three of an acrylic-, a styrene-, and a 
vinyl-containing group. 
The most preferred crosslinking agents are methacryloxyethyl vinyl 
carbonate, methacryloxyethyl vinyl carbamate, and methacryloxyethyl vinyl 
urea. 
Preferred novel hydrogen compositions incorporating the novel crosslinker 
include crosslinkers of the present invention, combined with at least one 
methacrylate-containing polyurethane-siloxane-containing monomer, and at 
least one (meth)acrylate or (meth)acrylamide-containing monomer and 
N-vinyl pyrrolidone. The polyurethane-siloxane-containing monomers may 
further comprise fluoroalkyl, fluoroether or alcohol-containing monomers. 
The preferred (meth)acrylates are alkyl methacrylate, 2-hydroxyethyl 
methacrylate, glycol methacrylate, polysiloxanylalkyl methacrylate and 
fluoroalkyl methacrylate, with (meth)acrylamide is N,N-dimethyl acrylamide 
being the most preferred. 
The most preferred bulky polysiloxyanyl methacrylate is methacryloxypropyl 
tris(trimethylsiloxy)silane, (TRIS). One preferred hydrogel composition 
further includes 2-vinyl-4,4-dimethyl-2-oxazolin-5-one (VDMO). 
Yet another preferred novel hydrogel composition enabled by the novel 
crosslinker of the present invention comprises at least one 
(meth)acrylate- or (meth)acrylamide-capped polysiloxane-containing 
monomer, a vinyl-containing monomer which may preferably be comprised of 
carbonate, carbamate and urea-containing polysiloxyanyalkylvinyl monomers, 
or a carboxylic acid-containing vinyl carbonate, vinyl carbamate or vinyl 
urea, and the crosslinking composition. 
Two preferred classes of silicone-containing monomers contemplated by the 
present invention are urethane-containing prepolymers, and ethylenically 
terminated polysiloxane containing monomers, such as, most preferably 
.alpha.,.omega.bis(methacryloxybutyl)polysiloxane (M.sub.2 D.sub.25). 
Another preferred hydrogel comprising the novel crosslinker composition 
further includes at least a (meth)acrylate-capped fluoroether-modified 
polysiloxane, a (meth)acrylate- or (meth)acrylamide-containing monomer and 
N-vinyl pyrrolidone (NVP). 
Further, it is envisioned that the new crosslinkers of this invention will 
react with all known monomers useful in the field of contact lenses, such 
as, for example HEMA systems, fluoroalkyl containing compositions, 
silicone- and non-silicone-containing compositions, urethane-containing 
compositions and silicone-containing compositions. 
The polymers of this invention can be formed into contact lenses by 
spincasting processes (such as those disclosed in U.S. Pat. Nos. 3,408,429 
and 3,496,254), cast molding processes (U.S. Pat. Nos. 4,084,459 and 
4,197,266), combinations of methods thereof, or any other known method for 
making contact lenses. Polymerization may be conducted either in a 
spinning mold, or a stationary mold corresponding to a desired contact 
lens shape. The lens may be further subjected to mechanical finishing, as 
occasion demands. Polymerization may also be conducted in an appropriate 
mold or vessel to form buttons, plates or rods, which may then be 
processes (e.g., cut or polished via lathe or laser) to give a contact 
lens having a desired shape. 
The hydrogels of the present invention are oxygen transporting, 
hydrolytically stable, biologically inert, and transparent. The monomers 
and prepolymers employed in accordance with this invention, are readily 
polymerized to form three dimensional networks which permit the transport 
of oxygen and are optically clear, strong and hydrophilic. 
The relative softness or hardness of the contact lenses fabricated from the 
resulting polymer of this invention can be varied by deceasing or 
increasing the molecular weight of the polysiloxane prepolymer end-capped 
with the activated unsaturated group or by varying the percent of the 
comonomer. Generally, as the ratio of polysiloxane units to end-cap units 
increases, the softness of the material increases. 
Any known silicone-containing prepolymer may be used in the process of this 
invention to form the silicone hydrogels of this invention, as will be 
apparent to one skilled in the art. The monomers added to the monomer mix 
to create the monomeric mixture may be monomers or prepolymers. 
A "prepolymer" is a reaction intermediate polymer of medium molecular 
weight having polymerizable groups. Thus it is understood that the terms 
"silicone-containing monomers" and "hydrophilic monomers" include 
prepolymers. Examples of such monomers may be found in U.S. Pat. Nos. 
4,136,250; 4,153,641; 4,740,533; 5,034,461; and 5,070,215. 
As with most random polymeric syntheses, the precise mechanism for the 
reaction of the new crosslinker with the desired acrylic-, vinyl-, and 
when desired, styrene-containing monomeric units is not completely 
understood. However, the resulting end-product polymer systems exhibit 
superior UV curing capabilities as compared with all known hydrogels to 
date. Therefore, the invention of this application contemplates all 
resulting polymeric systems made through reaction of desired monomers with 
the novel crosslinker, as well as the processes involved in achieving said 
end-result polymers. 
The appropriate amount of the crosslinker used is only dependent upon the 
desired properties of the resulting hydrogel, such as rigidity. Generally, 
the concentration of the crosslinker does not exceed 20% by weight of the 
total monomeric mix, preferably ranges from about 0.001% to about 10%, 
most preferably ranges from about 0.01% to about 5%, and in each instance 
should be enough to impart desired properties upon the resulting hydrogel. 
Typically, an amount of crosslinking agent is added which enables the 
resulting polymeric hydrogel to absorb water in the range from about 5% to 
about 90% by weight, preferably from about 10% to about 80%, and most 
preferably from about 20% to about 75%. 
Preferred contact lenses comprising the novel crosslinking composition of 
the present invention are oxygen permeable, hydrolytically stable, 
biologically inert, transparent, and can be "hard" or "soft" within the 
limits of these terms as is understood in the field. 
One preferred non-silicone-containing contact lens composition comprises at 
least one methacrylate such as 2-hydroxymethacrylate or a methyl 
methacrylate, a vinyl-containing monomer such as N-vinyl pyrrolidone and 
the crosslinking agent of the present invention. 
Polymerization of the monomer mixtures comprising the crosslinker of this 
invention may be performed in the presence of a diluent. The 
polymerization product will then be in the form of a gel. If the diluent 
is nonaqueous, the diluent must be removed from the gel and replaced with 
water through the use of extraction and hydration protocols well known to 
those skilled in the art. 
It is also possible to perform the polymerization in the absence of diluent 
to produce a xerogel. These xerogels may then be hydrated to form the 
hydrogels as is well known in the art. 
Notations such as "(meth)acrylate" or "(meth)acrylamide" are used herein to 
denote optional methyl substitution. Thus, the term methyl (meth)acrylate 
includes both methyl acrylate and methyl methacrylate. Similarly, the term 
N-alkyl (meth)acrylamide includes both N-alkyl acrylamide and N-alkyl 
methacrylamide. 
The terms "shaped article for use in biomedical applications" or 
"biomedical devices" mean the materials disclosed herein have 
physicochemical properties rendering them suitable for prolonged contact 
with living tissue, blood and the mucous membranes. These properties are 
required for biomedical shaped articles as already disclosed. It is known 
that blood, for example, is readily and rapidly damaged when it comes into 
contact with artificial surfaces. The design of a synthetic surface which 
is antithrombogenic and nonhemolytic to blood is necessary for prostheses 
and devices used with blood. 
Therefore, the polymers made from copolymerization with the crosslinkers of 
the present invention can be used to modify collagen to make blood 
vessels, urinary bladders surgical diagnostic devices and other such 
devices as disclosed in Kliment, U.S. Pat. No. 3,563,935. Also polymers 
can be used to make catheters as disclosed in Shephard U.S. Pat. No. 
3,566,874. These polymers can be used as semipermeable sheets for 
dialysis, artificial dentures and all of such disclosures as set forth in 
Stoy, U.S. Pat. No. 3,607,848. 
Further, the polymers and copolymers disclosed herein can be boiled and/or 
autoclaved in water without being damaged whereby sterilization may be 
achieved. Thus, an article formed from the disclosed polymers and 
copolymers may be used in surgery where an article compatible with living 
tissue or with the mucous membranes may be used. 
The following examples serve only to further illustrate aspects of the 
invention and should not be construed as limiting the invention. All parts 
and percents referred to herein are on a weight basis and all viscosities 
measured at 25 degrees C, unless otherwise specified. 
EXAMPLE 1 
Preparation of Crosslinker (HEMAVc) Derived from Reaction of Hydroxyethyl 
methacrylate and vinylchloroformate. 
A 500 ml round bottom flask equipped with reflux condenser, mechanical 
stirrer, thermometer, a dropping funnel and an efficient N.sub.2 blanket, 
was charged with 32.5 g of 2-hydroxyethyl methacrylate, 21.8 g of pyridine 
and 300 ml of chloroform. The contents were then cooled to less than 5 
degrees C with 25.3.g of vinyl chloroformate added via the dropping funnel 
while the contents were kept stirred and the temperature maintained below 
5 degrees C. The temperature was allowed to rise to ambient temperature 
and kept stirred overnight. The reaction mixture was then passed through a 
silica gel column and the contents was then dried with magnesium sulfate 
and filtered. The solvent was removed under reduced pressure (b.p. 74 C. 
at 1 mm torr) to give 26 g of named product. GC 99.2% purity. NMR spectrum 
confirmed the expected structure of the named product. 
EXAMPLE 2 
Preparation of 4-vinylphenyl vinyl carbonate 
A 500 ml round bottom flask equipped with a reflux condenser, a mechanical 
stirrer , a thermometer, a dropping funnel and an efficient N.sub.2 
blanket, is charged with 30.0 g (0.25 mole) of 4-vinylphenol, 21.8 g of 
pyridine and 300 ml of chloroform. The contents are then cooled down to 5 
degrees C., and 25,3 g of vinyl chloroformate is added dropwise via the 
dropping funnel with constant stirring and the temperature maintained at 5 
degrees or below. The temperature is then allowed to rise to ambient 
temperature and the mixture stirred overnight. The reaction mixture is 
then passed through a silica gel column and dried over magnesium sulfate 
and filtered. After the solvent is removed under pressure, the named 
product is recovered. 
EXAMPLE 3 
Preparation of methacryloxyethyl vinyl carbamate 
A 500 ml round bottom flask equipped with a reflux condenser, a mechanical 
stirrer, a thermometer, a with 32.5 g (0.25 mole) of HEMA, 21.8 g of 
pyridine, 50 mg of hydroquinone and 300 ml of chloroform. The contents are 
cooled down to 5 degrees or below. Vinyl isocyanate (13.3 g or 0.25 mole) 
in chloroform (30 ml) is added dropwise while the reaction contents were 
stirred and maintained below 5 degrees C. The reaction mixture is stirred 
for an additional 5 hours. The contents are then passed through a silica 
gel column, dried over magnesium sulfate and condensed. The residue is 
distilled under reduced pressure to recover the named product. 
EXAMPLE 4 
Preparation of 4-vinylphenyl vinyl carbamate 
The named is prepared by following the procedure as described in Example 3, 
except 2-hydroxyethyl methacrylate is replaced by 4-vinylphenol (30 g or 
0.35 mole). 
EXAMPLE 5 
Preparation of methacryloxyethyl vinyl carbamate 
A 1 liter round bottom flask equipped with a reflux condenser, a mechanical 
stirrer, a thermometer, a dropping funnel and an efficient N.sub.2 
blanket, is charged with 30.5 g (0.5 mole) 2-aminoethanol, 100mg of 
hydroquinone, 43.6 g of pyridine and 600 ml of chloroform. The contents 
are cooled down to between 0 and 5 degrees C. Through the dropping funnel, 
50.6 g (0.5 mole) of vinyl chloroformate in 100 ml of chloroform is added 
into the reaction flask at a rate such that the temperature is maintained 
at between 0 and 5 degrees C. The temperature is allowed to rise to room 
temperature with constant stirring overnight. The contents are then passed 
through a silica gel column, dried with magnesium sulfate and then 
evaporated. The residue is distilled under reduced pressure to recover 
2-hydroxyethyl vinyl carbamate. Then using the same equipment, 32.75 g of 
2-hydroxyethyl vinyl carbamate (0.25 mole), 50 mg of hydroquinone, 21.8 g 
of pyridine, and 300 ml of chloroform are added into the reaction flask 
and cooled to between 0 and 5 degrees C. Through a dropping funnel, 26.5 g 
(0.25 mole) of methacryloyl chloride in 50 ml of chloroform is added into 
the reaction flask at a rate such that the temperature is maintained 
between 0 and 5 degrees C. The temperature is then allowed to rise to room 
temperature and the contents stirred overnight. The contents are then 
passed through a silica gel column, dried with magnesium sulfate and 
evaporated. The final product is recovered by distillation under reduced 
pressure. 
EXAMPLE 6 
Preparation of methacryloyl vinyl urea 
A 500 ml 3-necked round bottom flask equipped with a reflux condenser, a 
mechanical stirrer, a thermometer, a dropping funnel and an efficient 
N.sub.2 blanket, is charged with 2-aminoethyl methacrylate hydrochloride 
41.4 g (0.25 mole), 50mg of hydroquinone and 300 ml of chloroform. The 
contents are cooled to between 0 and 5 degrees C. and stirred. Through a 
dropping funnel 25.3 g (0.25 mole) of triethylamine and 13.3 g (0.25 mole) 
of vinyl isocyanate in 50 ml of chloroform are added into the reaction 
flask and maintained at between 0 and 5 degrees C. The temperature is 
allowed to rise to room temperature with the contents stirred constantly 
overnight, passed through a silica gel column and dried with magnesium 
sulfate. The contents are then evaporated under reduced pressure to give 
the named product. 
EXAMPLE 7 
Preparation of 2-methacrylamidoethyl vinyl carbonate 
The named product is prepared by following the same procedure as that 
described in Example 1, except that 32.2 g (0.25 mole) of 2-hydroxyethyl 
methacrylamide is used in place of the 2-hydroxyethyl methacrylate. 
EXAMPLE 8 
Preparation of 2-methacrylamidoethyl vinyl carbamate 
The named product is prepared by following the same procedure as that 
described in Example 3, except that 32.2 g (0.25 mole) of 2-hydroxyethyl 
methacrylamide is used in place of the 2-hydroxyethyl methacrylate. 
EXAMPLE 9 
Preparation of 2-methacrylthioethyl vinyl carbamate 
A 500 ml round bottom, 3-neck flask equipped with a reflux condenser, a 
mechanical stirrer, a thermometer, a dropping funnel under an N.sub.2 
blanket, is charged with 2-aminoethyl thiol hydrochloride (Aldrich, 28.4 g 
or 0.25 mole), hydroquinone (50 mg), pyridine (21.8 g) and chloroform (300 
ml). The contents are cooled to 0-5 degrees C. Through the dropping 
funnel, methacryloyl chloride (26.5 g or 0.25 mole) in 50 ml of chloroform 
is added at a rate such that the temperature is maintained at between 0 
and 5 degrees C. The contents are then stirred overnight and passed 
through a silica gel column. The mixture is then charged into a new clear 
similarly equipped round bottom flask along with 50 mg of hydroquinone. 
The contents are cooled to between 0 and 5 degrees C. Through a dropping 
funnel, vinyl chloroformate, 25.3 g (0.25 mole), triethylamine (0.25 mole) 
and 50 ml of chloroform are added into the flask at a rate such that the 
temperature is maintained between 0 and 5 degrees C. The contents are then 
allowed to warm to room temperature and kept stirred overnight. The 
reaction mixture is passed through a silica gel column, dried with 
magnesium sulfate and condensed. The final product is recovered by 
distilling the residue under reduced pressure. 
EXAMPLE 10 
Preparation of decaethylene glycol methacrylate vinyl carbonate 
The named crosslinker is prepared by following the procedure as described 
in Example 1, except that 131.5 g (0.25 mole) of decaethylene glycol 
monomethacrylate (polysciences, Inc.) in the same stoichiometric amount is 
used to replace 2-hydroxyethyl methacrylate. 
EXAMPLE 11 
Preparation of decaethylene glycol methacrylate vinyl carbamate 
The named crosslinker is prepared by following the same procedure as 
described in Example 3, except that decaethylene glycol monomethacrylate 
in the same stoichiometric amount is used to replace 2-hydroxyethyl 
methacrylate. 
EXAMPLE 12 
Preparation of 4-methacrylamidophenyl vinyl carbonate 
The named compound is prepared by following the same procedure as that 
described in Example 7 except that 27.3 g (0.25 mole) 4-aminophenol is 
used to replace 2-amino ethanol in the reaction. 
EXAMPLE 13 
Preparation of 4-methacrylamidophenyl vinyl carbamate 
The named product is prepared by following the procedure set forth in 
Example 12 except that 13.3 g (0.25 mole) of vinyl isocyanate is used to 
replace vinyl chloroformate. 
EXAMPLE 14 
Preparation of 
1-(4-methacryloxybutyl)-3-(4-vinyloxycarboxybutyl)tetramethyl disiloxane 
A 500 ml 3-neck , round bottom flask equipped with a reflux condenser, a 
mechanical stirrer, a thermometer, a dropping funnel and a N.sub.2 
blanket, is charged with 69.5 g (0.25 mole) of 1,3-bis(4-hydroxybutyl) 
tetramethyl disiloxane (Silar Lab.), pyridine, 19.5 g and 300 ml of 
methylene chloride. The contents are cooled down to between 0 and 5 
degrees C. by an ice bath. Through the dropping funnel 25.3 g (0.25 mole) 
of vinyl chloroformate in 50 ml of methylene chloride is added dropwise 
into the flask at a rate such that the temperature is maintained between 0 
and 5 degrees C. The contents are then stirred for another 4 hours and 
then passed through a silica gel column. The eluents are condensed and 
injected in 6-8 gram portions into a reverse phase high performance liquid 
chromatography unit (Waters), using acetonitrile as solvent. Three 
fractions are collected. The major (center) fraction from each injection 
is collected and condensed to give 1,3-bis(4-hydroxybutyl)tetramethyl 
disiloxane monovinyl carbonate. The monovinyl carbonate product (34.8 g or 
0.1 mole) is charged into a flask as already described, along with 8.0 g 
of pyridine, 50 mg of hydroquinone and 200 ml of chloroform. The contents 
are cooled down to between 0 and 5 degrees C. Through a dropping funnel, 
10.5 g (0.1 mole) of methacryloyl chloride in 50 ml of chloroform is added 
into the flask at such a rate that the temperature is maintained between 0 
and 5 degrees C. The contents are stirred continuously for 4 hours and 
then passed through a silica gel column. The contents are then condensed 
and distilled under reduced pressure to give the named product. 
Hydroquinone (50 mg) is added into the named product. 
EXAMPLE 15 
Preparation of 
-(4-vinyloxycarboxybutyl)dimethylsilyl-(4-methacryloxybutyl)dimethylsiloxy 
polysiloxane 
A one liter, 3-neck round bottom flask equipped with a reflux condenser and 
mechanical stirrer, is charged with the 8.08 g (0.02 mole) of the 
crosslinker prepared according to the method as described in Example 14, 
and 35.52 g (0.12 mole) octamethylcyclotetrasiloxane. 
EXAMPLE 16 
Preparation of 2,2,3,3-tetrafluoro-1,4-butanediol methacrylate vinyl 
carbonate 
The named compound is prepared according to the procedure described in 
Example 14, except that 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane is 
replaced by 40.5 g (0.25 mole) of 2,2,3,3,-tetrafluoro-1,4-butanediol 
(PCR, Inc.) 
EXAMPLES 17-22 
Formulations Containing HEMA and NVP (Non-silicone) 
The HEMA used in formulations (Examples) 17 and 18 contained 0.06% ethylene 
glycol dimethacrylate (EGDMA). In both of Examples 17 and 18, two films 
were cast. Formulations 17A and 18A were subjected to both a thermal heat 
cure followed by a UV cure. Formulations 17B and 18B were subjected to 
only UV curing. The HEMA used in formulations (Examples) 19 and 22 
contained 0.15% EGDMA. The formulations were subjected to curing 
conditions comprising either only UV for one hour, or UV followed by a 
heat postcure at 120 degrees C. for one additional hour. The UV initiator 
used was benzoin methyl ether (BME) or Darocure-1173 (EM Industries). The 
thermal initiator used was tertbutyl peroctoate (TBO). The films were cast 
between two glass plates, followed by boiling water extraction and then 
placed in a phosphate buffered saline before evaluating physical 
characteristics. 
______________________________________ 
Formulation Examples 
(parts) 17 18 19 20 21 22 
______________________________________ 
HEMA 72 72 72 72 72 72 
NVP 28 28 28 28 28 28 
BME 0.076 0.076 -- -- -- -- 
TBO 0.100 0.100 -- -- -- -- 
Darocur -- -- 0.2 0.2 0.2 0.2 
HEMAVc -- -- -- -- 0.2 -- 
EGDMA -- 20 -- 20 20 20 
Glycerin 20 -- 20 20 20 20 
______________________________________ 
Curing Type 
Examples 
Formulation 
17A 17B 18A 18B 19 20 21 22 
______________________________________ 
UV yes yes yes yes yes yes yes yes 
Heat yes no yes no no no no no 
______________________________________ 
Film Examples 
Properties 
17A 17B 18A 18B 19 20 21 22 
______________________________________ 
% Extr 18 78 5.2 13.1 13.0 12.8 10.7 12.2 
% Water 54 80 56 55.3 56.2 56.7 58.4 54.0 
Modulus 25 -- 28.8 23.5 25.5 24.1 17.1 28.7 
Tear 3.0 -- 2.6 4.4 4.4 4.7 3.2 2.1 
______________________________________ 
RESULTS 
The results show that the formulation using the novel crosslinker, HEMAVc 
(Example 21) was able to produce films with a lower amount of extractables 
and increased water content, while being cured with only UV. These results 
are believed to show better incorporation of HEMA with NVP under only a UV 
cure regimen when the novel crosslinker, HEMAVc is present. The hydrogel 
lens made from this formulation (Example 21) gave an optical quality of 
4.8 out of a 5.0 scale which was far superior to the only comparative 
formulation cast into lenses (Example 17) which had a 4.0 optical clarity 
rating. 
EXAMPLES 23-30 
To further exemplify the enhanced performance of the novel crosslinker, 
HEMAVc as compared with traditional crosslinkers, such as EGDMA, the 
formulations from Examples 21 and 22 were further modified by adding 
increased concentrations of HEMAVc. All films cast were UV cured for one 
hour followed by standard extraction procedures as already described. The 
following properties were noted. 
______________________________________ 
Examples 
23 24 25 26 27 28 29 30 
______________________________________ 
HEMAVc 0.2 0.4 0.8 1.6 0.2 0.4 0.8 1.6 
Conc. 
Film 
Properties 
% Extract 
10.7 7.8 7.1 5.7 12.2 8.0 7.6 6.9 
% Water 58.4 57.7 55.8 53.7 54.0 54.6 53.5 50.7 
Modulus 17 22 38 60 29 42 53 87 
Tear 3.2 3.0 2.3 2.5 2.1 1.6 1.5 1.6 
______________________________________ 
EXAMPLE 31-36 
Preparation of Non-Silicone-Containing Hydrogels with HEMAVc 
To further exemplify the usefulness of the crosslinking agent of the 
present invention with varied polymeric systems, HEMAVc was used as the 
crosslinking agent in non-silicone-containing formulations containing both 
a hydrophilic methacrylate (HEMA) and a hydrophobic methacrylate 
(4-t-butyl-2-hydrxycyclohexyl methacrylate, or TBE) and NVP. All 
formulations were cured with UV and the resulting films were optically 
clear. The properties of the films cast from the various formulations are 
shown in the following table: 
______________________________________ 
Example 
Formulation 31 32 33 34 35 36 
______________________________________ 
HEMA 55 55 55 50 45 40 
NVP 45 45 45 50 55 60 
HEMAVc .3 .3 .3 .3 .3 .3 
DAROCURE .2 .2 .2 .2 .2 .2 
GLYCERIN 20 20 20 20 20 20 
TBE 5 10 15 15 20 20 
Properties 
% Extract 6.8 4.9 5.9 5.2 8.1 8.1 
% Water 69 63 59 67 64 64 
Modulus 13 17 46 18 680 490 
Tear 2.6 4.7 12.1 6.5 high high 
______________________________________ 
EXAMPLE 37 
Preparation of Polyurethane-silicone Hydrogels 
A monomer mix for a polyurethane hydrogel containing the following 
components was prepared: 
a) urethane prepolymer, derived from isophorone diisocyanate, diethylene 
glycol, polysiloxanediol of molecular weight 3600 and end-capped with HEMA 
(IDS3H), 30 parts; 
b) 3-methacryloxypropyl tris(trimethylsiloxy)silane, (TRIS), 30 parts; 
c) NVP, 40 parts; 
d) n-hexanol; and 
e) Darocur-1173, 0.2 parts. 
To a portion of the above-identified formulation was added 0.6 part HEMAVc. 
Both mixes were then processed into hydrogel films by placing the mix 
between two glass plates and curing under UV for 2 hours followed by 
extraction with ethanol for 4 hours followed by boiling water for 4 hours. 
The hydrogel films were then placed in a phosphate buffered saline (pH 
7.4) solution. The following properties were noted. 
______________________________________ 
Formulation 
Properties without HEMAVc 
with HEMAVc 
______________________________________ 
% Extract 16 10 
% water 25 37 
Oxygen Perm, Dk 
144 105 
Modulus, g/mm.sup.2 
970 430 
______________________________________ 
The formulation containing the novel crosslinker exhibited improved 
characteristics such as lower extractables, higher water content and lower 
modulus without sacrificing much oxygenpermeability. 
EXAMPLE 38 
A monomer mix was prepared, derived from the following 
IDS3H/TRIS/NVP/DMA/HEXANOL/DAROCUR-1173 ats the following weight ratios 
25/25/35/15/40/0.2. Formulations "A" through "I" were established with 
"A" being the comparative control containing no crosslinker, "B" through 
"E" containing progressively increasing amounts of HEMAVc, and "F" through 
"I" containing progressively increasing amounts of EGDMA. The mixes were 
then cast into hydrogel films using procedures as earlier described. The 
film properties for each formulation were noted and are produced in the 
following table: 
______________________________________ 
Formulation 
A B C D E F G H I 
Crosslinker 
HEMAVc EGDMA 
______________________________________ 
weight 
0 0.1 0.2 0.4 0.8 0.1 0.2 0.4 0.8 
% Ext 15.9 12.6 11.2 8.2 6.1 16.2 14.5 14.1 13.2 
% 47.4 49.3 51.4 50 47.0 46.1 46.5 45.0 43.4 
H.sub.2 O 
Mod. 56 51 59 67 98 60 66 74 119 
______________________________________ 
RESULTS 
In the formulations containing HEMAVc, extractables and modulus values were 
comparatively lower, and the water content values comparatively higher 
than the formulations which did not contain HEMAVc. 
EXAMPLE 39 
Casting Hydrogel Films--HEMA/NVP Formulation Containing HEMAVc 
A formulation containing hydroxyethyl methacrylate (HEMA) which in turn 
contained 0.17% ethyleneglycol dimethacrylate (EGDMA) 72 parts; 
1-vinyl-2-pyrrolidone (NVP), 28 parts; hydroxyethyl methacrylate 
vinylchloroformate, 0.08 parts; Darocur-1173 [EM Industries], 20 parts; 
and hexanol, 20 parts was prepared. This formulation was cast between two 
silane-treated glass plates and cured under UV radiation for 2 hours. 
After solvent (ethanol) extraction, the weight loss was 14.5%, which was 
accountable for the weight of the hexanol. The films after hydration 
contained 65% water, indicating excellent polymerization. 
EXAMPLE 40 
HEMA/NVP Formulation without HEMAVc 
The mix containing HEMA/EGDMA/NVP/Benzoin methylether 
(BME)/t-butylperoxyoctoate (TBO) (71.85/0.15/28/0.75/0.1) was cast into 
lenses by first exposing to ultraviolet radiation (UV) for 2 hours, 
followed by 120 degree C heat postcure for 1 hour. The resulting lenses 
were then extracted with boiling water. The boiling water extractables was 
18% and the final water content of the lens was 56.5%. When comparing the 
data from HEMAVc modified formulation and the standard formulation, it was 
believed that more NVP was incorporated into the hydrogel in the HEMAVc 
modified formulation. Most importantly, the copolymerization or curing for 
the HEMAVc-modified formulation can be achieved by exposure to UV 
radiation alone, instead of using a heated post-cure regimen as is 
required for the standard formulation. 
EXAMPLE 41 
Urethane Hydrogels for Contact Lens Applications 
A monomer mix containing the following ingredients was prepared. 
a) 30 parts urethane prepolymer derived from isophorone diisocyanate, 
diethylene glycol, polysiloxanediol of molecular weight 3600 
b) 30 parts of TRIS 
c) 30 parts of NVP 
d) 10 parts of DMA 
e) 0.1 parts of crosslinker HEMAVc 
f) 0.2 parts of Darocure-1173 
g) 40 parts of solvent hexanol 
This formulation was cured under UV radiation for 2 hours to form films, 
which were then extracted with ethanol, dried and boiled in water, 
followed by saturation in buffered saline at pH 7.4. The hydrogel films 
had a modulus value of 80 g/mm2, oxygen permeability of 98 in Dk units, 
and water content of 41%. 
EXAMPLE 42 
Urethane Hydrogel Formulation Containing NVP, DMA, VDMO and HEMAVc 
A monomer mix containing the same ingredients in the same weight ratio as 
that in Example 41 except that 10 parts of 
2-vinyl-4,4-dimethyl-2-oxazoline-5-one (VDMO) was added. The formulations 
can be processed into the hydrogel films of Example 10. The hydrogel films 
had a modulus value of 110 g/mm.sup.2. Oxygen permeability of 90 (Dk 
units) and a water content of 40%. 
EXAMPLE 43 
Urethane Hydrogel Lens Casting 
A polyurethane mix of the formulation as described in Examples 41 and 42 
was filtered through a disposable filter into a clean vial. Under an inert 
nitrogen atmosphere, 60-90 microliters of the mix was injected onto a 
clean plastic mold half and then covered with a second plastic mold half. 
The molds were then compressed and cured for 90 minutes in the presence of 
UV light (4200 microwatts/cm.sup.2). The molds were then opened 
mechanically and put into a beaker containing aqueous ethanol. The lenses 
were released from the molds within 1 hour, then extracted with ethanol 
for 48 hours, and boiled in distilled water for 4 hours. The resultant 
lenses were inspected for cosmetic quality, cytotoxicity and dimension. 
Lenses passing inspection were thermally disinfected in phosphate buffered 
saline prior to on-eye evaluation. 
EXAMPLE 44 
Clinical Evaluations 
The cast-molded polyurethane lenses described in Example 43 were evaluated 
on six to 10 patients. In each test, a poly(HEMA) control lens was worn on 
one eye and the test lens on the other eye. The lenses were analyzed after 
a minimum of one hour, and preferably 5 hours or longer for wettability 
and surface deposition study. The surface wettability rating scale was 0-4 
with 0 representing no surface deposit and 4 representing multiple 
deposits of 0.5 mm diameter or larger. The results for the lenses of the 
formulation of Example 41, was 3.0 for wetting and 0.4 for deposits after 
5 hours of wear. For lenses comprising 1 part VDMO (Example 42 
formulation), the results showed a wettability rating of 3.3 and a deposit 
rating of 0.7 after 4 hours of wear. 
EXAMPLE 45 
Formulation Containing M.sub.2 D.sub.25 /TRIS/NVP/HEMAVc 
An .alpha.,.omega.-Bis(methacryloxybutyl)polysiloxane (M.sub.2 D.sub.25) 
was prepared from the reaction of 1,3-Bis(4-methacryloxybutyl)disiloxane 
and 1,1,3,3,5,5-hexamethyl trisiloxane in molar ratio of 1:8.33. Thirteen 
parts of M.sub.2 D.sub.25 was combined with 47 parts of TRIS, 40 parts of 
NVP, and 0.1 part of HEMAVc was shaken and produced a clear solution. To 
this mixture was added 40 parts of hexanol and 0.2 parts of Darocure-1173. 
Twenty (20) parts of hexanol was added to the mixture along with 0.2 parts 
of BME. The resultant formulation was cast onto glass plates and cured 
under UV light for 2 hours. The films were extracted with solvent 
(ethanol) overnight, boiled in water for 4 hours, and then placed in 
buffered saline at pH 7.4. These films exhibited the following properties: 
water content--23%; modulus 369 g/mm2; contact angle--20 degrees; and 
oxygen permeability 114 in Dk units. 
EXAMPLE 46 
Formulation Containing M.sub.2 D.sub.25 /TRIS/NVP/DMA/HemaVc 
A glass vial contained the above-listed ingredients in the following 
amounts: (13/47/30/10/0.1). The content was cast into hydrogel films 
according to the procedure described in Example 45. The resultant hydrogel 
films exhibited the following properties: water content--24%; modulus 146 
g/mm2; contact angle 25 degrees; and oxygen permeability 113 in Dk units. 
EXAMPLE 47 
Comparative Formulation--M.sub.2 D.sub.25 /NVP/DMA/HemaVc 
A formulation was prepared containing the same weight ratio as that in 
Example 46 immediately above, except that TRIS was replaced completely by 
an additional amount of M.sub.2 D.sub.25 (60/30/10/0.1). The resulting 
mixture was cast into hydrogel films according to the procedure described 
in Example 39 The resultant films exhibited a modulus of 570 g/mm2 (which 
is about 1.5 times greater than the modulus displayed by the hydrogel 
films prepared as described in Example 14 which contained both M.sub.2 
D.sub.25 and TRIS in the specified weight ratio of 13 to 47. 
EXAMPLES 48-53 
Six polyurethane hydrogel films containing the following ingredients, were 
prepared: 
a) urethane prepolymer, derived from isophorone diisocyanate, diethylene 
glycol, polysiloxanediol of molecular weight 3600 and HEMA, 30 parts; 
b) TRIS, 30 parts; 
c) NVP, varied from 0 to 40 parts; 
d) DMA, varied from 40 to 0 parts (NVP+DMA=40 parts) 
e) HEMAVc crosslinker at 0.3% of NVP amount; 
f) n-Hexanol 40 parts; 
g) Darocur-1173, (UV initiator), 0.2 part. 
These formulations were UV cured, followed by ethanol extraction and 
boiling water hydration, to give resultant hydrogel films with the 
following properties (water content and modulus). FIG. 1 depicts the 
resultant films of Examples 48-53 as shown in Table 1, with each film as 
one plotted point respectively. 
TABLE 1 
______________________________________ 
Example 
48 49 50 51 52 53 
______________________________________ 
NVP/DMA ratio 
40/0 38/2 35/5 30/10 20/20 0/40 
% water 35 46 44 41 41 37 
Modulus 430 281 150 80 79 63 
______________________________________ 
RESULTS 
FIG. 1 depicts the resultant film of Examples 54-57, with the 
modulus/composition relationship of each film plotted as one point 
respectively. 
EXAMPLES 54-57 
Polyurethane formulations of the ingredients as in Examples 48-53 but of 
different relative parts, as shown in Table 2, were prepared. 
a) IDS3H & b) TRIS, 34 parts each; 
c) NVP & d) DMA, 32 parts combined; 
e) n-Hexanol, f) HEMAVc and g) Darocure-1173, same parts as in Examples 
48-53. 
The formulations were cast and processed in the same manner as in Examples 
48-53, with the water content and modulus data shown in Table 2. FIG. 2 
depicts the resultant film of Examples 54-57, with each film as one 
plotted point respectively. 
TABLE 2 
______________________________________ 
Example 
54 55 56 57 
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NVP/DMA ratio 32/0 24/8 16/16 0/32 
water % 25 26 31 25 
Modulus 610 275 107 87 
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The modulus/composition relationship is further shown in FIG. 2. 
EXAMPLES 58-61 
M.sub.2 D.sub.x -based Hydrogel Films 
The following silicone-containing hydrogel formulations were prepared and 
cast processed into hydrogel films by the procedure of Examples 48-53 The 
ingredients were: 
a) M.sub.2 D.sub.25, 13 parts 
b) TRIS, 47 parts 
c) NVP & d) DMA, 40 parts combined 
e) n-Hexanol, 40 parts 
f) HEMAVc, 0.3 part of NVP amount 
g) Darocure, 0.2 part 
The formulations were cast and processed in the same manner as in Examples 
48-53, with the water content and modulus data shown in Table 3. FIG. 3 
depicts the resultant film of Examples 58-61, with each film as one 
plotted point respectively. 
TABLE 3 
______________________________________ 
Example 
58 59 60 61 
______________________________________ 
NVP/DMA ratio 40/0 30/10 20/20 0/40 
water % 23 24 32 29 
Modulus 370 150 110 90 
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Many other modifications and variations of the present invention are 
possible to the skilled practitioner in the field 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.