TITLE: Dimethylacrylamide-copolymer hydrogels with high oxygen permeability.
European Patent Application EP0351364 A2

ABSTRACT:
This invention describes polymers which are obtained by
copolymerization of 15-85 wt % N,N-dimethylacrylamide with about 15-85
% of a fluorinated monomer such as perfluoroalkyl-alkylene acrylate or
-methacrylate with from 3 to 25 fluorine-atoms and optionally, 0-50 wt
% other acrylates or methacrylates and 0-20 wt %, but not more than 5
mol % of a polyvinyl functional crosslinking agent. These polymers are
machinable in the dry state and form clear hydrogels with about 25-75
wt % water content and which possess oxygen-permeabilities 3-7 times
higher than conventional hydrogels of similar water content. In the
absence of crosslinking, the novel polymers are plasticized by water,
forming clear hydroplastics with 30-70 wt % water content. The
crosslinked polymers are especially useful for fabricating contact
lenses for extended wear by either cutting and polishing a xerogel
button, or by spin casting or direct molding in bulk or in solution.

INVENTORS:
Mueller, Karl F.

APPLICATION NUMBER: EP19890810499
PUBLICATION DATE: 01/17/1990
FILING DATE: 06/30/1989

ASSIGNEE: CIBA GEIGY AG (CH)
INTERNATIONAL CLASSES: G02C7/04; A61F9/00; A61L15/00; A61L26/00; A61L27/00; A61L27/16;
A61L27/52; A61M37/00; C08F20/22; C08F20/52; C08F212/14; C08F220/22;
C08F220/54; C08F220/56; C08F290/12; C08G18/62; C08G18/81; G02B1/04;
(IPC1-7): A61K9/06; A61L15/16; A61L25/00; A61L27/00; C08F212/14;
C08F220/22; C08F220/54; G02B1/04
EUROPEAN CLASSES: A61L26/00B2+C08L33/00; A61L26/00H7; A61L27/16+C08L33/00; A61L27/52;
C08F220/22; C08F220/54; G02B1/04B2+C08L33/00

DOMESTIC PATENT REFERENCES:
EP0228193 N/A

FOREIGN REFERENCES:
WO/1988/005060A1 WETTABLE, HYDROPHILIC, SOFT AND OXYGEN PERMEABLE
  COPOLYMER COMPOSITIONS

OTHER REFERENCES:
PATENT ABSTRACTS OF JAPAN, vol. 11, no. 332 (C-455)Ä2779Ü, 29th October
1987; & JP-A-62 115 009 (SANYO ELECTRIC CO.) 26-05-1987

CLAIMS:
1. A copolymer, having the characteristics of high clarity, high
hydrophilicity, and high oxygen permeability and which is, in the water
swollen hydrated state, soft and flexible, which copolymer comprises
the polymerization product of, with weight percent based on the total
weight of monomers (a), (b), (c) and (d), of (a) 15-85 percent by
weight of N,N-dimethylacrylamide, (b) 15-85 percent by weight of a
vinyl monomer containing at least three fluorine atoms selected from
the group consisting of the acrylate or methacrylate esters of formula
B1: EMI23.1 wherein R<1> is hydrogen or methyl, n is an integer from
1-4, m is an integer from 0-11, X is hydrogen or fluorine; with the
proviso that, when m is zero, X is fluorine; and of hexafluoroisopropyl
acrylate, hexafluoroisopropyl methacrylate, undecafluoro
cyclohexyl-methyl methacrylate and 2, 3,4,5,6-pentafluorostyrene, (c) 0
to 50 percent by weight of a copolymerizable vinyl monomer other than
the monomer of component (b), and (d) 0 to 20 percent by weight, but
not more than 5 mol percent based on the combined moles of monomers
(a), (b), (c) and (d), of a crosslinking agent having at least two
copolymerizable vinyl groups.
2. A copolymer according to claim 1 which is the polymerizataion
product of (a) 25 to 80 percent by weight of N,N-dimethylacrylamide,
(b) 20 to 75 percent by weight of a vinyl monomer selected from the
group consisting of the acrylate or methacrylate esters of formula B1
and hexafluoroisopropyl methacrylate, (c) 0 to 40 percent by weight of
a copolymerizable vinyl monomer other than the monomer of component
(b), and (d) 0.01 to 16 percent by weight, but not more than 4 mol
percent, based on combined moles of monomers (a), (b), (c) and (d), of
a crosslinking agent having at least two copolymerizable vinyl groups.
3. A copolymer according to claim 1 which is the polymerization product
of (a) 24.9 to 70 percent by weight of N,N-dimethylacrylamide, (b) 19.9
to 65 percent by weight of a vinyl monomer selected from the group
consisting of the acrylate or methacrylate esters of formula B1 and
hexafluoroisopropyl methacrylate, (c) 10 to 40 percent by weight of a
C1-C12-alkyl acrylate or methacrylate, a C5-C12-cycloalkyl acrylate or
methacrylate, a C2-C4-hydroxy-alkyl acrylate or methacrylate, a
C1-C4-alkoxy-C2-C4-alkyl acrylate or methacrylate, or an
oligosiloxanyl-silylalkyl acrylate or methacrylate containing 2 to 10
silicon atoms, and (d) 0.1 to 3 percent by weight of a crsslinking
agent having at least two copolymerizable vinyl groups.
4. A copolymer according to claim 1 wherein based on the total weight
of copolymer, component (a) is 35 to 55 percent by weight, component
(b) is 15 to 55 percent by weight, component (c) is 10 to 40 percent by
weight, and component (d) is 0.1 to 2 percent by weight.
5. A copolymer according to claim 1 wherein component (d) is 5 to 20
percent by weight.
6. A copolymer according to claim 1 wherein component (d) is 0 percent
by weight.
7. A copolymer according to claim 1 wherein component (b) is
hexafluoroisopropyl methacrylate, undecafluorocyclohexyl
methylmethacrylate or a fluorinated acrylate or methacrylate of formula
B1 where X is fluorine.
8. A copolymer according to claim 1 wherein component (b) is a
fluorinated methacrylate of formula B1 where X is fluorine, n is 1 or
2, and m is 1 to 7, and component (c) is 10 to 40 percent by weight.
9. A copolymer according to claim 8 wherein in component (b) R<1> is
methyl.
10. A copolymer according to claim 8 wherein component (c) is methyl
methacrylate, trimethyl-cyclohexyl methacrylate,
methoxy-ethylmethacrylate, 2-hydroxyethylmethacrylate or a mixture
thereof.
11. A copolymer according to claim 8 wherein component (c) is
methoxyethyl methacrylate or a mixture of methoxyethyl methacrylate and
2-hydroxyethyl methacrylate.
12. A copolymer according to claim 1 wherein component (b) is a
fluorinated acrylate of formula B1 where X is fluorine, and component
(c) is 0 percent by weight.
13. A copolymer according to claim 1 wherein component (c) is 5 to 30
percent by weight of an oligosiloxanyl-silylalkyl methacrylate having 3
to 7 silicon atoms.
14. A copolymer according to claim 13 wherein component (c) is
tris(trimethylsiloxanyl-silyl)propyl methacrylate.
15. A copolymer according to claim 1 wherein component (c) is 0.1 to 10
percent by weight of an ethylenically unsaturated carboxylic acid, an
ethylenically unsaturated sulfonic acid, a tertiary di-C1-C2-alkyl
aminoalkylacrylate or methacrylate or a hydroxy-C2-C4-alkylacrylate or
methacrylate.
16. A copolymer according to claim 5, wherein component (d) is a
poly(vinyl alcohol-co-ethylene) reacted with 0.1-10 mol % of a vinyl
unsaturated isocyanate, preferably with 2-isocyanato ethyl
methacrylate.
17. A hydrated composition according to any of claims 1 to 16 in form
of an ophthalmic prosthetic device.
18. A hydrated composition according to any of claims 1 to 16 in form
of a bandage.
19. A composition according to any of claims 1 to 16 in form of a drug
delivery device.
20. A hydrated composition according to any of claims 1 to 16 in the
form of a contact lens.

DESCRIPTION:
Dimethylacrylamide-Copolymer Hydrogels with High Oxygen Permeability
Hydrogels and their use as contact lenses have been known since at
least Wichterle et al. published U.S. Patent No. 3,220,960, which
discloses sparingly crosslinked, hydrated poly(hydroxyalkyl
methacrylate), typified by poly(2-hydroxyethyl methacrylate)
(poly-HEMA) with a water content of about 39 %.
Poly-HEMA became the standard material for hydrogel contact lenses
since it is hard enough to be easily fabricated by machining and
polishing in the dry state, yet soft and comfortable to wear in the
water swollen state.
In subsequent developments other hydrophilic monomers were used, most
commonly N-vinyl-pyrrolidone (NVP) copolymers with methyl-methacrylate
(MMA) or other "high Tg" methacrylates. With this system, hydrogels
with water contents up to 80 % can be prepared. Dimethylacrylamide
copolymers provide similar properties and have been described as well.
The oxygen transmissibility of such conventional hydrogel contact
lenses is determined by their water content and thickness and can be
improved by increasing the water content or by decreasing thickness.
Both strategies have been used to increase O2-permeability and to make
extended-wear contact lenses, but both strategies lead to lenses with
insufficient strength which are easily damaged. It is highly desirable
to have a hydrogel soft lens with the same or similar good mechanical
properties and as comfortable to wear as poly-HEMA, yet with
substantially higher oxygen permeability. This can now be achieved by
incorporation of either siloxane groups or fluorinated groups into the
polymer compositions.
It would be especially desirable to have highly fluorinated hydrogels
since, while siloxane groups give slightly higher oxygen permeability,
fluorinated groups allow the manufacture of polymers with higher dry
hardness and therefore better machinability while at the same time
reducing lipophilicity and deposit formation on the hydrated polymer.
Among prior art compositions consisting of fluorinated hydrogels the
following patents are relevant:
U.S. Patent Nos. 4,433,111 and 4,493,910 describe hydrogels and contact
lenses obtained by copolymerization of 20-40 mol % substituted or
unsubstituted acrylamide or methacrylamide; 25-55 mol %
N-vinylpyrrolidone (NVP); 5-20 mol % hydroxy-alkyl(meth)-acrylate; 1-10
mol % (meth)-acrylic acid, and 1-9 mol % of a
perfluoroalkyl-alkylene(meth)-acrylate; the perfluoroalkyl groups act
to reduce protein deposition.
U.S. Patent No. 4,640,965 describes hydrogels and contact lenses
obtained by copolymerization of hydroxyfluoroalkylstyrene (5-60 %, by
weight), with hydroxyalkyl (meth)-acrylates or N-vinylpyrrolidone
(40-95 %, by weight); the hydroxy group is necessary to attain the
required compatibility.
U.S. Patent No. 4,638,040 describes the synthesis of
1,3-bis(trifluoroacetoxy)propyl-2-methacrylate polymers and their use
as hydrogel-contact lens materials and ocular implants after
hydrolysis.
U.S. Patent No. 4,650,843 describes hydrogel contact lens materials
consisting essentially of copolymers of 50-95 % (by weight) of
2-hydroxyethyl-methacrylate and 5-35 % (by weight) of fluorinated
methacrylates with up to 5 F-atoms.
In all these cases the range of clear compositions is very limited; the
commercially available fluorinated (meth)acrylates can be incorporated
in only relatively small amounts; alternatively, complicated, for
instance hydroxylated F-monomers have to specially be synthesized to
achieve better solubility in NVP or HEMA (U.S. 4,640,965). It has now
unexpectedly been discovered that N,N-dimethylacrylamide when used as
comonomer with fluorine-containing monomers gives clear copolymers
within a wide range of possible compositions.
This has been especially surprising since N-vinyl pyrrolidone (NVP),
which has a solubility parameter, polarity and hydrogen-bonding
capacity very similar to dimethylacrylamide (DMA), does not give clear
compatible mixtures under the same conditions. [The solubility
parameters (cal/cm<3>)<1/2> for the analogous saturated molecules are:
N,N-dimethylacetamide, C4H9ON: 10.8, moderate H-bonding;
N-methylpyrrolidone, C5H9ON; 11.3, also moderately H-bonding]. In
addition, the copolymerization between DMA and acrylates and
methacrylates in general proceeds much smoother because of more
favorable reactivity-ratios, leading to a more random copolymer
structure for DMA-copolymers than for NVP-copolymers.
This, together with the good compatibility of DMA with fluorinated
(meth)acrylates allows synthesis of highly O2-permeable hydrogels which
are harder than the corresponding silicone-hydrogel copolymers and,
because of the oleophobic nature of fluorinated groups, more resistant
to soiling and deposit formation.
Crosslinked dimethylacrylamide copolymers with other acrylic or
methacrylic monomers and their use as conventional hydrogel-soft
contact lenses are described in U.S. Patent Nos. 4,328,148, 4,388,428
and 4,388,436.
Among silicone containing hydrogels of the prior art, U.S. Patent Nos.
4,139,692 and 4,139,513 specify tri-siloxy-hydroxyalkylmethacrylate,
with the OH-group required for compatibility; DMA is not exemplified,
but is claimed together with HEMA and NVP.
U.S. Patent Nos. 4,182,822 and 4,343,927 claim C1-C4-dialkylacrylamide
hydrogel-copolymers with oligosiloxanylsilyl-alkylene methacrylates,
but without examplifying DMA copolymers.
Dimethylacrylamide (DMA) has not been used prior to this invention as
the major hydrophilic monomer in silicone- and/or fluorine containing
hydrogels.
It has further been discovered that the DMA-copolymers of this
invention, if prepared in the absence of a crosslinking agent, form
linear, clear polymers which are plasticized, but not dissolved in
water. They can therefore in their water plasticized state
(hydroplastic) easily be molded, coated or formed into shapes and
subsequently crosslinked. This represents another practical method for
manufacturing hydrogel articles.
The instant invention pertains to a copolymer, having the
characteristics of high clarity, high hydrophilicity, high oxygen
permeability and which is, in the water swollen hydrated state, soft
and flexible, which copolymer comprises the polymerization product of,
with weight percent based on the total weight of monomers (a), (b), (c)
and (d), of (a) 15-85 percent by weight of N,N-dimethylacrylamide, (b)
15-85 percent by weight of a vinyl monomer containing at least three
fluorine atoms selected from the group consisting of the acrylate or
methacrylate esters of formula B1:
EMI4.1 wherein R<1> is hydrogen or methyl, n is an integer from 1-4, m
is an integer from 0-11, X is hydrogen or fluorine; with the proviso
that, when m is zero, X is fluorine; and of hexafluoroisopropyl
acrylate, hexafluoroisopropyl methacrylate, undecafluoro
cyclohexyl-methyl methacrylate and 2,3,4,5,6-pentafluorostyrene, (c) 0
to 50 percent by weight of a copolymerizable vinyl monomer other than
the monomer of component (b), and (d) 0 to 20 percent by weight, but
not more than 5 mol percent based on the combined moles of monomers
(a), (b), (c) and (d), of a crosslinking agent having at least two
copolymerizable vinyl groups. Preferably m is an integer from 1 to 11.
Preferred copolymers are those which are the polymerization product of
(a) 25 to 80 percent by weight of N,N-dimethylacrylamide, (b) 20 to 75
percent by weight of a vinyl monomer selected from the group consisting
of the acrylate or methacrylate esters of formula B1 and
hexafluoroisopropyl methacrylate, (c) 0 to 40 percent by weight of a
copolymerizable vinyl monomer other than the monomer of component (b),
and (d) 0.01 to 16 percent by weight, but not more than 4 mol percent,
based on combined moles of monomers (a), (b), (c) and (d), of a
crosslinking agent having at least two copolymerizable vinyl groups.
A further embodiment are copolymers which are the copolymerization
product of 24.99 to 75 percent by weight of (a), 24.99 to 75 percent by
weight of (b), 0 to 30 percent by weight of (c), and 0.01 to 16 percent
by weight, but not more than 4 mol percent, of (d).
Still more preferred copolymers are those which are the polymerization
product of (a) 24.9 to 70 percent by weight of N,N-dimethylacrylamide,
(b) 19.9 to 65 percent by weight of a vinyl monomer selected from the
group consisting of the acrylate or methacrylate esters of formula B1
and hexafluoroisopropyl methacrylate, (c) 10 to 40 percent by weight of
a C1-C12-alkyl acrylate or methacrylate, a C5-C12-cycloalkyl acrylate
or methacrylate, a C2-C4-hydroxy-alkyl acrylate or methacrylate, a
C1-C4-alkoxy-C2-C4-alkyl acrylate or methacrylate, or an
oligosiloxanyl-silylalkyl acrylate or methacrylate containing 2 to 10
silicon atoms, and (d) 0.1 to 3 percent by weight of a crosslinking
agent having at least two copolymerizable vinyl groups.
A further embodiment are copolymers which are the copolymerization
product of 34.9 to 65 percent by weight of (a), 34.9 to 65 percent by
weight of (b), 0 to 30 percent by weight of (c), and 0.1 to 3 percent
by weight of (d).
Especially preferred copolymers are those where, based on the total
weight of copolymer, component (a) is 35 to 55 percent by weight,
component (b) is 15 to 55 percent by weight, component (c) is 10 to 40
percent by weight, and component (d) is 0.1 to 2 percent by weight.
Also preferred copolymers of the instant invention are those where
component (d) is 5 to 20 percent by weight. Other preferred copolymers
are those wherein component (d) is 0 percent by weight.
Other preferred copolymers of the instant invention are those where
component (b) is hexafluoroisopropyl methacrylate,
undecafluoro-cyclohexylmethyl methacrylate or a fluorinated acrylate or
methacrylate of formula B1 where X is fluorine.
Other preferred copolymers are those where component (b) is a
fluorinated methacrylate of formula B1 where x is fluorine, n is 1 or 2
and m is 1 to 7, and component (c) is 10 to 40 percent by weight. Most
preferably component (c) is methyl methacrylate or trimethyl cyclohexyl
methacrylate, methoxy-ethyl methacrylate, methoxy-ethylacrylate,
2-hydroxy-ethyl methacrylate or mixtures thereof.
Still other preferred copolymers are those where component (b) is a
fluorinated acrylate of formula B1 where X is fluorine, and component
(c) is 0 percent by weight.
Other preferred copolymers are those where component (b) is a
fluorinated methacrylate of formula B1 where R<1> is methyl, X is
fluorine, n is 2, and m is 5 to 9, and component (c) is 10 to 30
percent by weight. Most preferably component (c) is methyl methacrylate
or trimethyl cyclohexyl methacrylate.
Still other preferred copolymers are those where component (b) is a
fluorinated acrylate of formula B1 where R<1> is hydrogen, and X is
fluorine, and component (c) is 0 percent by weight.
Other preferred copolymers of the instant invention are those where
component (c) is 5 to 30 percent by weight of an
oligosiloxanylsilylalkyl methacrylate having 3 to 7 silicon atoms. Most
preferably component (c) is tris(trimethyl-siloxanyl)-silylpropyl
methacrylate.
Still other preferred copolymers are those wherein component (c) is 0.1
to 10 percent by weight of an ethylenically unsaturated carboxylic
acid, an ethylenically unsaturated sulfonic acid, tertiary
di-C1-C2-alkylamino alkyl acrylate or methacrylate or a hydroxy-C2-C4
alkyl acrylate or methacrylate.
Hereinbefore and hereinafter, alkyl or alkoxy, if not specified
otherwise, has preferably 1 to 7, more preferred 1 to 4, carbon atoms.
Preferred F-containing monomers (b) are: hexafluoroisopropyl acrylate
(F6A) and methacrylate (F6MA); heptafluoropropyl-methyl acrylate (F7A)
and methacrylate (F7MA); nonafluorobutyl-methyl and -ethyl acrylate and
methacrylate; C6F13-methyl and -ethyl acrylate and methacrylate,
C8F17-and C10F21 methyl- and ethyl acrylate and methacrylate. These
monomers can be used alone or in combination with each other.
Most preferred are the monomers hexafluoroisopropyl methacrylate,
heptafluorobutyl methacrylate and C6-C10perfluoroalkyl-ethyl acrylate
and methacrylate.
Comonomers of component (c) include a wide variety of conventional
polymerizable hydrophobic and/or hydrophilic vinyl monomers, such as
vinyl (C1-C12) alkyl ethers, vinyl (C4-C16) alkenoic acids, styrene,
(C1-C12) alkyl, hydroxy substituted (C2-C12) alkyl, alkoxy-alkyl and
polyalkoxy-alkyl and (C6-C12) mono- or bi-cycloaliphatic fumarates,
maleates and especially acrylates, methacrylates, acrylamides and
methacrylamides, as well as acrylic and methacrylic acid, the
corresponding amino or mono- or di-(lower alkyl) amino substituted
acrylic monomers; and vinyl-(C4-C7) lactams.
Typical monomers are: 2-hydroxyethyl-, 2-hydroxypropyl-,
3-hydroxypropyl acrylate and methacrylate; N-vinylpyrrolidone;
N,N-dimethylaminoethyl methacrylate; methyl-, ethyl-, propyl-,
isopropyl-, butyl-, sec.butyl-, tert.butyl-, cyclohexyl-,
trimethylcyclohexyl-, tert.butyl cyclohexyl-, isobornyl acrylate and
methacrylate; methoxyethyl-, ethoxyethyl, methoxy-ethoxyethyl,
ethoxy-ethoxyethyl acrylate and methacrylate, styrene;
(meth)acrylamides like N,N-dimethyl-methacrylamide,
N,N-diethyl(meth)-acrylamide, 2-hydroxyethyl-, 2-hydroxypropyl-,
3-hydroxypropyl-acrylamide and methacrylamide; isopropyl, n-propyl
acrylamide and methacrylamide, and glycidyl (meth)acrylate.
Vinyl sulfonic acid, styrene sulfonic acid and
2-methacrylamido-2-methyl propane-sulfonic acid can be used in small
amounts as comonomers, especially if the polymerization is carried out
in solution.
Also useful as comonomers are the known
oligosiloxanyl-silylalkylene(meth)acrylates with an oligosiloxy group,
branched or linear, containing from 2 to 10 Si-atoms, whose terminal
groups are methyl, ethyl or phenyl, for example:
triphenyl-dimethyl-disiloxy-methyl (meth)acrylate;
pentamethyldisiloxymethyl (meth)acrylate;
methyl-di(trimethylsiloxy)silylpropylglyceryl (meth)acrylate;
heptamethyl-cyclotetrasiloxymethyl (meth)acrylate; heptamethyl
cyclotetrasiloxypropyl (meth)acrylate; (trimethylsilyl)
decamethylpentasiloxy propyl (meth)acrylate; and tris(trimethylsiloxy)
silylpropyl methacrylate.
Preferred among the other copolymerizable monomers of component (c)
which can be present in amounts ranging from 0-50 %, preferably up to
40 %, are tris-(trimethylsiloxy silyl)-propyl methacrylate and alkyl
methacrylates whose homopolymers have a high glass transition
temperature, such as methyl-, cyclohexyl-, isopropyl-, tert-butyl-,
trimethylcyclohexyl- and -isobutyl methacrylate, as well as
2-hydroxyethyl methacrylate, styrene, acrylamide, and methacrylamide.
Also preferred are methoxy-ethyl acrylate and methoxy-ethyl
methacrylate and ethoxy-ethyl methacrylate.
Most preferred are methyl methacrylate and
tris-(trimethyl-siloxy-silyl)propyl methacrylate and methoxyethyl
methacrylate.
The crosslinking agents of component (d) which can be present in
amounts up to 20 % by weight are conventional polyvinyl-, typically di-
or tri-vinyl-monomers, most commonly the di- or tri(meth)acrylates of
dihydric or higher hydric alcohols, such as ethyleneglycol-, diethylene
glycol-, triethylene glycol-, tetraethylene glycol-, propylene glycol-,
butylene glycol-, hexane-1,6-diol-, thio-diethylene glycol-diacrylate
and methacrylate; neopentyl glycol diacrylate; trimethylolpropane
triacrylate and the like; N,N min -dihydroxyethylene-bisacrylamide and
-bismethacrylamide; also diallyl compounds like diallylphthalate and
triallyl cyanurate; divinylbenzene; ethylene glycol divinyl ether.
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).
This list is only examplary and not meant to be exhaustive.
Also useful are polymeric crosslinking agents, like polyether-bis
urethane-dimethacrylates as described in U.S. Patent No. 4,192,827 or
obtained by reaction of polyethylene glycol, polypropylene glycol or
polytetramethylene glycol with 2-isocyanatoethylmethacrylate (IEM) or
m-isopropenyl- alpha , alpha -dimethylbenzylisocyanate(m-TMI), and
polysiloxane-bis urethane-dimethacrylates as described in U.S. Patent
Nos. 4,486,577, and 4,605,712, and which can be present in amounts up
to 20 %. Also useful are the reaction products of poly(vinyl alcohol),
ethoxylated polyvinyl alcohol or of poly(vinyl alcohol-co-ethylene)
with 0.1 to 10 mol % vinyl isocyanates like IEM or m-TMI.
Preferred crosslinking agents are ethylene glycol dimethacrylate,
diethylene glycol dimethacrylate, 1,4-butane diol di(meth)acrylate,
neopentyl glycol diacrylate; and poly(vinyl alcohol-co-ethylene)
reacted with 0.1-10 or 1-10 mol % 2-isocyanato ethyl methacrylate; most
preferred is ethylene glycol dimethacrylate.
When present, component (d) is preferably present in an amount of at
least 0.01 parts by weight, based on the total weight of the comonomer
mixture.
The copolymers of this invention are clear, hydrophilic and highly
oxygen permeable. They can swell in water to form hydrogels with 25 to
75 % water and are useful in a variety of applications, such as gas
separation membranes or as oxygen permeable wound dressings or
bandages; due to their clarity and high oxygen permeability they are
especially suited for soft contact lenses useful for daily or extended
wear. They are also useful as carriers for the controlled delivery of
drugs either as dermal patches, orally taken beads, body implants or
eye inserts.
The novel polymers are prepared by free-radical polymerization either
in bulk or in solution and using heat- or UV-activated initiators.
Typical heat activated initiators are preferably peroxides or azo
catalysts having a half-life at the polymerization temperature of at
least 20 minutes. Typical useful peroxy compounds include: isopropyl
percarbonate, tert-butyl peroctoate, benzoyl peroxide, lauroyl
peroxide, decanoyl peroxide, acetyl peroxide, succinic acid peroxide,
methyl ethyl ketone peroxide, tert-butyl peroxyacetate, propionyl
peroxide, 2,4-dichlorobenzoyl peroxide, tert.-butyl peroxypivalate,
pelargonyl peroxide,
2,5-dimethyl-2,5-bis(2-ethylhexanoyl-peroxy)hexane, p-chlorobenzoyl
peroxide, tert-butyl peroxybutyrate, tert-butyl peroxymaleic acid,
tert-butyl-peroxyisopropyl carbonate,
bis(1-hydroxy-cyclohexyl)peroxide; azo compounds include:
2,2 min -azo-bis-isobutyro-nitrile; 2,2 min
-azo-bis(2,4-dimethylvaleronitrile); 1,1 min -azo-bis (cyclohexane
carbonitrile), 2,2 min azo-bis(2,4-dimethyl-4-methoxyvaleronitrile).
Other free radical generating mechanisms can be employed, such as
X-rays, electron-beams and UV-radiation. Preparation of contact-lens
blanks by UV radiation in the presence of a photoinitiator such as
diethoxyacetophenone, 1-hydroxycyclohexyl phenyl ketone,
2,2-dimethoxy-2-phenylacetophenone, phenothiazine, diisopropylxanthogen
disulfide, benzoin, benzoin methyl ether and other benzoin derivatives
is a preferred method.
The novel copolymers can be prepared in form of sheets or films by
casting the monomer solutions in the appropriate molds or by casting a
film with a knife- or roller coater and subsequently carrying out the
polymerization either using UV or heat. It is also possible to prepare
the polymers in form of round beads of 0.01 to 2.0 mm diameter by
suspension polymerization in aqueous brine, as f.i. described in U.S.
Patent No. 4,224,427.
The polymers can be fabricated into any desired shape such as contact
lenses by direct molding or by spin-casting either in bulk or in the
presence of a solvent.
For contact-lens manufacture, the polymer is usually prepared in shape
of a rod, button or sheet or some other desired shape by exposing the
closed and filled mold to heat, typically throughout a 3-24 hour cycle
of increasing temperatures, from 30-120 DEG C. The finished article can
subsequently be further shaped during cutting and polishing steps. For
use as a contact lens, the polymer is preferably crosslinked. In the
absence of a crosslinking agent, the resulting polymer is soluble or
plasticizable in solvents and can be used as a coating or be
thermo-formed.
The polymerization can also be carried out in solvents, with or without
a polyvinyl-crosslinking agent. Typical solvents include alcohols such
as methanol, ethanol, isopropanol, butanol and tert-butanol; esters
such as isopropyl acetate; ketones such as acetone, methyl ethyl
ketone, methyl propyl ketone, methyl isopropyl ketone, cyclohexanone;
amides such as N,N-dimethylformamide, N,N-dimethylacetamide,
N-methylpyrrolidone; or dimethylsulfoxide; ethers such as ethoxy-,
methoxy- and butoxy-ethanol; ethylene glycol dimethyl- and diethyl
ether; methoxyethyl acetate; ethylene- and propylene carbonate.
Solution polymerizations are preferably carried out in an inert
atmosphere at temperatures between 30 and 80 DEG C, dependent on
initiator and solvent, for 3-24 hours. The polymer solutions can be
used directly to form coatings which can subsequently be crosslinked if
a suitable reactive group has been built into the polymer, such as a
UV-reactive group or an epoxy group.
Freshly distilled monomers are used for all experiments in the working
Examples. Tris(trimethylsiloxysilyl)-propyl methacrylate (Si4MA) is
obtained from Shin-Etsu Corporation; perfluoroalkyl-ethyl acrylates
(RfA) and methacrylate (RfMA) are obtained from American Hoechst
Corporation with the following average Rf-chain-length distribution:
C6F12 < 5 %; C8F17 about 60 %; C10F21 about 25 %, C12F25 about 10 %.
All other monomers are obtained from commercial supply houses
(N,N-dimethylacrylamide = DMA; ethylene glycol dimethacrylate = EGDMA;
methylmethacrylate = MMA).
In the following examples, water content is expressed as: EMI12.1
Physical-mechanical measurements are carried out on an INSTRON testing
machine, model 1123.
Oxygen permeability measurements are carried out using a CREATECH
Permeometer, model 201T, in air, and are expressed as EMI12.2
Temperatures are given in Celsius degrees. Example 1:
5g N,N-Dimethylacrylamide (DMA), 4.95 g heptafluorobutyl methacrylate
(F7MA) and 0.05 g ethylene glycol dimethacrylate (EGDMA) are mixed
together with 0.02 g benzoin methyl ether (BME). The mixture is
degassed, kept under dry nitrogen and with a pipette filled into round
polypropylene button molds having a height of 10 mm and a 12 mm
diameter. The mold is capped with a polypropylene cap and the filled
molds are set into a tray and exposed to UV-radiation from a SYLVANIA
BlackLite-Blue lamp, while sparging the UV-radiation box with dry
nitrogen, first only from below for 2 hours, followed by another hour
from top and bottom. The finished buttons are tempered for 1 hour at
110 DEG C, cooled to room temperature and pulled out of the mold.
From one of the clear, hard buttons a 0.25 mm slice is cut off for
oxygen permeability measurements after equilibration in water, and a
thicker, SIMILAR 2 mm slice is cut off for swelling measurements.
The remainder of the button is used to determine dry Shore-D hardness
and, after 1 week equilibration in water, wet Shore-A hardness.
The polymer prepared above has a Shore-D hardness (dry) of 87, a
Shore-A hardness of 15, a water content (H2O, % by weight) of 58 and an
O2.DK of 30 barrers.
For comparison, a poly-(2-hydroxyethyl methacrylate) hydrogel has a
water content of 39 % and an O2.DK of 6.5 barrers. Example 2-6:
The procedure of example 1 is repeated with 10 g each of the monomer
compositions listed below and the properties of the clear copolymers
are determined.
Columns=8> Head Col 1: Ex. No. Head Col 2 to 4: Composition <1)> Head
Col 5: Head Col 6 to 7: Shore Hardness Head Col 8: O2.DK SubHead Col
1>: SubHead Col 2 to 4 RB=2: (% by weight) SubHead Col 5>H2O: SubHead
Col 6>Dry: SubHead Col 7>Wet: SubHead Col 8>barrers: SubHead Col 1:
SubHead Col 2: DMA SubHead Col 3: F7MA SubHead Col 4: EGDMA SubHead Col
5: % SubHead Col 6: D SubHead Col 7:
A 15049.90.158871530 25049.90.548852028 34851.80.247852525
44752.80.246853024 54554.80.247864222 64058.80.2328575- <1)>F7MA:
heptafluorobutyl methacrylate
EGDMA: ethylene glycol dimethacrylate
Examples 7-18:
The procedure of example 1 is repeated with 10 g of the monomer mixture
listed below. All copolymers are clear and their properties are listed
below.
Columns=9> Head Col 1: Ex. No. Head Col 2 to 5: Composition <1)> Head
Col 6: H2O Head Col 7 to 8: Shore Hardness Head Col 9: O2.DK SubHead
Col 1>: SubHead Col 2 to 5 RB=2: (% by weight) SubHead Col 6>%: SubHead
Col 7>Dry: SubHead Col 8>Wet: SubHead Col 9>barrers: SubHead Col 1:
SubHead Col 2: DMA SubHead Col 3: Si4MA SubHead Col 4: FnMA (n) SubHead
Col 5: EGDMA SubHead Col 6: SubHead Col 7: D SubHead Col 8:
A 7503019.5(7)0.549823628 8502029.8(7)0.257842341
9452529.8(7)0.243823237 10451539.8(7)0.247842533
11404019.8(7)0.242785039 12403029.8(7)0.243804030
13402534.8(7)0.240823936 Head Col 1: Ex.
No. Head Col 2 to 5: Composition <1)> Head Col 6: H2O Head Col 7 to 8:
Shore Hardness Head Col 9: O2.DK SubHead Col 1>: SubHead Col 2 to 5
RB=12: (% by weight) SubHead Col 6>%: SubHead Col 7>Dry: SubHead Col
8>Wet: SubHead Col 9>barrers: DMASi4MAFnMA (n) EDGMADA
14404019.8(6)0.231804532 15403029.8(6)0.234807921
16453519.8(6)0.247813239 17473319.8(6)0.248823038
18503019.8(6)0.250832137 <1)>FnMA with n = 7: heptafluorobutyl
methacrylate
FnMA with n = 6: hexafluoroisopropyl methacrylate
Si4MA: tris-(trimethylsiloxanyl-silyl)-propyl methacrylate
EGDMA: ethylene glycol dimethacrylate
Example 19:
The procedure of example 1 is repeated, using 5g DMA, 4.95 g
pentafluorostyrene and 0.05 g EGDMA. A clear, hard polymer is obtained
(Shore-D = 85) which absorbs 22 % by weight of water and has an O2-DK
of 6 barrers. Examples 20-21:
Using the procedure of example 1, clear copolymers of DMA with
Si4MA<1)> and Rf-A<1)> are prepared, having the compositions and
properties listed below: EMI15.1
The polymer buttons of example 20 are easily by machining and polishing
and equilibration in water fabricated into contact lenses.
In contrast to example 20, mixtures of either 50 % N-vinylpyrrolidone
or of N-vinylacetamide with 50 % Rf-A are found to be completely
immiscible, even in the monomeric state. Examples 22-30:
With the monomer solutions of the examples listed in the table below,
flat polymer sheets are prepared by pouring the mixtures containing 0.1
% by weight benzoin methyl ether (BME) as initiator into glass molds
lined with clear MYLAR TM , sheets and using 0.5 mm silicone-cord as
spacer, held together by spring clamps. The molds are exposed to UV
radiation for 4 hours, followed by 1 hour annealing at 100 DEG C. The
clear sheets are swollen in water and their physical-mechanical
properties determined on an INSTRON testing machine, model 1123.
A separate fraction of the mixtures described above is used to fill
polypropylene contact lens molds and cured by UV as described. The
resulting contact lenses are, clear, wettable and optically flawless
after equilibration in water.
Columns=9 Head Col 1: Ex. No. Head Col 2: Polymer of Ex.
No. Head Col 3 to 5: Composition Head Col 6: H2O Head Col 7 to 9:
INSTRON-data SubHead Col 1>: SubHead Col 2>: SubHead Col 3 to 5 RB=2:
(% by weight) SubHead Col 6>%: SubHead Col 7 RB=2>Tensile St.: SubHead
Col 8 RB=2>Youngs Mod.: SubHead Col 9>Elongation: SubHead Col 1>:
SubHead Col 2>: SubHead Col 3 RB=3>DMA: SubHead Col 4 RB=3>Si4MA:
SubHead Col 5 RB=3>FnMA <1)> : SubHead Col 6>: SubHead Col 7 to 8 RB=3:
Kg/cm<2> SubHead Col 9>%: SubHead Col 1>: SubHead Col 2>: SubHead Col 3
to 5 RB=4: (% EGDMA up to 100 %) SubHead Col 1: SubHead Col 2: SubHead
Col 3: SubHead Col 4: SubHead Col 5:
FnMA n = 7 22545-54.84713.322.3455 23447-52.84613.99.8425
24348-51.84711.95.8455 25-50-49.54815.710.2264 26-503019.5507.06.8182
SubHead Col 6: SubHead Col 7: SubHead Col 8: SubHead Col 9: SubHead Col
10: FnMA n = 6 27-453519.84710.323.1469 28-473319.84814.210.7459 RfA
29-50-49.85013.810.2478 30-503019.8476.92.2622 <1)>FnMA: n = 7:
heptafluorobutyl methacrylate
n = 6: hexafluorisopropyl methacrylate
RfA: Rf-ethylene acrylate with Rf chain length distribution given in
example 20-21.
Examples 31-32:Synthesis of linear, water plasticized fluorinated
hydroplastic. Example 31:
5 g F7MA and 5 g DMA are dissolved in 10 g ethanol together with 0.02 g
2,2 min -azo-bis(2,4-dimethylvaleronitrile)(VAZO-52) and stirred under
nitrogen in a bottle on a constant-temperature bath for 24 hours.
The resultant viscous solution is dried to yield 10 g of a clear
copolymer which is equilibrated in distilled water to a viscous
hydroplastic with 48 % by weight of H2O. Example 32:
The procedure of example 31 is repeated, using 10 g Rf-A with the
structure and Rf-chain length distribution given in Example 20, 10 g
DMA, 1 g dodecylthiol, 10 g ethanol and 5 g methyl ethyl ketone (MEK).
A highly viscous syrup is obtained which on equilibration in excess
water gives a low viscosity hydroplastic with 55 % by weight of H2O.
Examples 33-34:Synthesis of hydrogels by casting with a solvent
4.25 g heptafluorobutyl methacrylate (F7MA), 4.25 g DMA and 1.5g
poly(ethylene-co-vinylalcohol) (EVA) (32 mol % ethylene; 28,000 MW),
which has previously been reacted as a 10 % solution in
N-methylpyrrolidone with 5 mol % isocyanatoethyl methacrylate
(EVA-IEM), are dissolved by stirring in N-methylpyrrolidone to make a
50 % solution. 0.1 g benzoin methyl ether is added and dissolved. The
mixture is degassed, sparged with dry nitrogen and poured into a mold
(0.5 mm spaces between Mylar TM lined glass plates), followed by
exposure to UV for 12 hours. The clear sheet is removed, equilibrated
in distilled water until all N-methylpyrrolidone is extracted, and
tested as described.
The same procedure is repeated, but using as comonomers a mixture of
equal parts tris-(trimethylsiloxanyl silyl)-propyl methacrylate (Si4MA)
and F7MA.
The clear polymers have the following properties:
Columns=7> Head Col 1: Ex. No. Head Col 2 to 5: Composition Head Col 6:
H2O Head Col 7: O2.DK SubHead Col 1>: SubHead Col 2 to 5 RB=2: (% by
weight) SubHead Col 6>%: SubHead Col 7>barrers: SubHead Col 1: SubHead
Col 2: DMA SubHead Col 3: F7MA SubHead Col 4: Si4MA SubHead Col 5:
EVA-IEM 334141-183913 344120.520.5183923
A separate fraction of the mixtures described above is used to fill
polypropylene contact lens molds and cured by UV as described. The
resulting contact lenses are clear, wettable and optically flawless
after equilibration in water. Examle 35: Synthesis of anionic and
amphoteric hydrogels.
Using the same procedure as described in examples 33 and 34, two
hydrogels are synthesized using as comonomers 2-methacrylamido-2-methyl
propane-sulfonic acid (AMPS) and N,N-dimethylaminoethyl methacrylate
(DAMA). The polymer compositions and their equilibrium water contents
are shown below.
Columns=7> Head Col 1: Ex. No. Head Col 2 to 6: Composition Head Col 7:
H2O SubHead Col 1>: SubHead Col 2 to 6 RB=2: (% by weight) SubHead Col
7>%: SubHead Col 1: SubHead Col 2: DMA SubHead Col 3: F7MA SubHead Col
4: EVA-IEM SubHead Col 5: AMPS SubHead Col 6: DAMA 35a44.337.613.44.7
-63 35b44.337.613.42.7 2.046 Example 36-37:
Using the procedure of example 1, the following compositions are
synthesized and tested.
Columns=8 Head Col 1: Ex. No. Head Col 2 to 4: Composition Head Col 5
to 6: Shore Hardness Head Col 7: H2O Head Col 8: O2.DK SubHead Col 1>:
SubHead Col 2 to 4 RB=2: (% by weight) SubHead Col 5>Dry: SubHead Col
6>Wet: SubHead Col 7>%: SubHead Col 8>barrers: SubHead Col 1: SubHead
Col 2: DMA SubHead Col 3: Rf-A <1)> SubHead Col 4: EGDMA SubHead Col 5:
D SubHead Col 6: A SubHead Col 7: SubHead Col 8: SubHead Col 9: n = 8
365049.80.2822648.726.4 SubHead Col 10: SubHead Col 11: SubHead Col 12:
n = 6-12 375049.80.2822648.4726.0 <1)>n = 8: C8F17-CH2CH2 acrylate
n = 6-12: Rf-distribution shown in Example 20
Both polymers are water clear in the dry and water swollen state.
Examples 38-49: Use of Rf-ethylene methacrylates as comonomers.
The compositions listed in the following table are synthesized in form
of buttons and as 0.5 mm thick sheets, as described in example 1 and
22-30. The buttons are used to measure hardness and oxygen
permeability, and the sheets for testing mechanical-physical
properties.
All polymers, except where noted, are clear in the water swollen state.
EMI20.1 Examples 50-53: Hydrogels with increased crosslink density and
other comonomers.
The polymers listed in the following table are synthesized in form of
buttons and 0.5 mm thick sheets, and their swelling and
physico-mechanical properties are determined, as described in example 1
and 22-30.
Columns=10> Head Col 1: Ex. No. Head Col 2 to 6: Composition <1)> Head
Col 7: Shore Head Col 8: H2O Head Col 9: Shore Head Col 10: O2.DK
SubHead Col 1>: SubHead Col 2 to 6 RB=2: (% by weight) SubHead Col 7>D:
SubHead Col 8>%: SubHead Col 9>A: SubHead Col 10>barrers: SubHead Col
1: SubHead Col 2: DMA SubHead Col 3: RfMA SubHead Col 4: MMA SubHead
Col 5: TMMA SubHead Col 6:
EGDMA SubHead Col 7: (dry) SubHead Col 8: SubHead Col 9: (wet)
505024.7524.75-0.58558.333 24.2 515024.524.5-1.08654.743 22.1
525024.024.0-2.08649.557 21.6 534534.8-200.28346.645 28.1 <1)>DMA:
N,N-dimethylacrylamide
RfMA: as described in Examples 38-49
MMA: methyl methacrylate
TMMA: trimethyl cyclohexyl methacrylate
Example 54:
5g N,N-dimethylacrylamide, 3.98 g Rf-ethyl acrylate with the Rf-chain
length distribution shown in example 20, 1.0 g 2-hydroxyethyl
methacrylate, 0.02 g ethylene glycol dimethacrylate and 0.02 g benzoin
methyl ether are mixed together, degassed in vacuo and sparged with dry
nitrogen; the mixture is filled into a MYLAR TM , lined glass mold
using 0.5 mm silicone cord as spacer. The mold is exposed to UV
radiation from a SYLVANIA BlackLite-Blue Lamp for 5 hours, after which
it is taken apart. The clear polymer sheet is equilibrated in water; it
is tough, strong and resilient, with a water content of 60 % and an
oxygen permeability, 02.DK of 32 barrers. Examples 55-57:
40 g N,N-dimethylacrylamide, 24.75 g C6F13CH2CH2-methacrylate, 10.00 g
2-hydroxyethyl methacrylate, 0.5 g ethylene glycol-dimethacrylate and
24.75 g of an alkoxy-ethylacrylate or methacrylate (M-4) as listed in
the table are mixed, together with 0.2 g benzoin methyl ether. Buttons
are prepared in molds as described in example 1 and tested. The results
are shown in the table.
Columns=8> Head Col 1: Ex.
No. Head Col 2: M-4 Head Col 3: Shore-D Hardness Head Col 4: H2O Head
Col 5: T.S. Head Col 6: Y.M. Head Col 7: el. Head Col 8: O2.DK SubHead
Col 1>: SubHead Col 2>: SubHead Col 3>: SubHead Col 4>%: SubHead Col 5
to 6 RB=2: (kg/cm<2>) SubHead Col 7>%: SubHead Col 8>barrers: 55MOMA
<1)> 8459 3.52.218724 56MOA <2)> 8064 3.52.019828 57EOMA <3)> 8357
7.81.819022 <1)>methoxy-ethyl methacrylate <2)>methoxy-ethyl acrylate
<3)>ethoxy-ethyl methacrylate
Example 58:
A polymer button prepared in example 55 is cut and polished in form of
a contact lens, and subsequently equilibrated in phosphate buffered
saline solution, resulting in a 14.5 mm diameter, oxygen permeable soft
contact lens.