Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~vo ~91/1~428~ 1 2 0 ~ O ~ 1 9 P~/US90/0~032
SOFT GAS PERMEA~LE CONTACT LEMS
HAVING IMPROVED CLINI CAL PERFORMANCE
. . .
BACKGROUND_OF THE INVENTION
This application is a continuation-in-part of prior
applications, Serial Nos. 07/407,261, ~iled September 14,
1989;.07/132,174, filed December 14, 1987 (which in turn
is a con~inuation-in-part of prior application Serial Mo.
OQ1,149, filed January 7, 1987); and 07/381,587, filed
July 18, 1989.
The present invention relates to contact lenses,
and more particularly to hydrophilic soft gas permeable
contact lenses having improved clinical performance.
.;
Among the most important properties and require-
ments of contact lenses axe substantial permeabili~y to
oxygen (commonly referred to as DK ~, and a highly wettable
: and deposition-resistan~ surface~
.
The development and use of plastic materials and
compositions for contact lenses has been the subject of
much attention over the years.
Among the firs~ such developments was the so-called
hard lens utilizing the hard plastic polymethylmethacry-
late (P~MAI. However, this material does not exhibit a
significant degree of oxygen permeability and has very
poor surface wettability characteristicsO The art then
progressed to soft lenses based upon poly 2-hydroxyethyl
methacrylate (poly HEMA), a material having significantly
better oxygen permeability and surface quality than the
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hard PMMA plastic. Neverth~less, these characteristics
were still not as high as desirable or necessary, and
lenses of this type often resulted in serious problems of
coxneal staining, swelling, ulcers, thickness and
infection.
Somewhat more recently, based upon better under-
standing of the corneal reguirement o~ substantial oxygen
permeability, the art proposed the use of so-called hard
gas permeable (HGP) lenses composed of either of two types
o~ plastic materials, acrylic silicone or acrylic fluoro-
silicone. See, e.g., U~S. Patent No. 3,~08,178. General-
ly, the oxygen permeabili~y of H~P lenses can progressive-
ly be increased with increasing amoun~s of the silicone
and/or fluorosilicone in the- composition; at the sarne
time, however, the surface wettability of the lens becomes
progressively poorer. In order to overcome this problem,
it is known to incorporate a relatively large amount of
methacrylic acid (MAAi, an ionic material, into the formu-
lation, resulting in the lens surface being negatively
charged to a certain extent. While this expedient does
lead to improved surface wettability, the negatively-
charged surface has a very high absorptivity leading to
serious deposition problems. As a conse~uence, the HGP
lens is of only limited potential.
Most recently, hydrophilic soft gas permeable (SGP)
lenses have been developed based upon compositions contain
ing, e.g., a polymeri~able vinylic siloxane monvmer and a
hydrophilic vinylic monomer. See, eOg., U.S. Patent Nos .
4,136,250; 4,182,82~; 4,261,875; 4,343,927; 4,~26,389;
4,486,577; 4,605,712; 4,711,943 and 4,837,289. The SGP
lenses of this type, which generally have a water content
of from about 25 ~o 75% by weight, have excellent oxysen
permeability and hydrophilicity. Surprisingly, however,
thé clinical performance of SGP lenses, includlng
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~09~283 2 0 ~ 0 41 9 PCT/VS90/0SD32
3~
functional (i.e., on the eye) wettability, deposition
resistance, dehydration resistance and/or comfort, is very
poor, making such lenses unsuitable for extended wear.
. . . . . . .... . .
Thus, notwithstanding the advances made to date,
-
there still exists a need for plastic contact lenses of
the SGP type which not only possess a high degree of
oxygen permeability, but also exhibit excellent clinical
performance, such as functional wettability, deposition
resistance, and com~ort, thus making the lenses suitable
for extended wear. The foregoing is the principal object
of the invention.
SUMMARY OF THE INVENTION
This and other objec~s are achieved in the present
invention by the provision of a soft gas permeable contact
lens, composed of the polymerization produet of composi-
tions containing a polymerizable vinylic siloxane monomer
and a hydrophilic vinylic monomer, having on the lens
surface a proportion of hydroxy acrylic monomer units to
silicon units sufficient to provide an SGP lens having the
requisite high DK, softness and rebound elasticity, and
which at the same time possess a high degree of clinical
performance, thus rendering the lenses eminently suitable
for long-term extended wear~
The requisite sufficient proportion of hydroxy
acrylic monomer units to silicon units on the lens surface
can be attained by surface treatment o the lens in order
to increase hydroxy acrylic monomer units and~or to reduce
the silicon units on the surface. In preferred e~bodi-
ments of the invention, the surface treatment is carried
out either by reaction on the lens surface with a polyhyd-
ric alcohol (polyol) and/or base or acid, ox by radiation
treatment of the lens to graft, deposit or coat hydroxy
acrylic monomer uni'-s on L he sur~ac2 thereof.
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WO91/~2g3 I~ a~ P~T/US90/05032
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It should be noted that the present invention
differs signi~icantly from prior art practices related to
the provision, or attemp~ed provision, of a hydrophilic
surface on a hydrophobic lens. Thus, hydrophobic lenses
are known in the art which are made of silicone rubber, a
cross-l.inked polysiloxane, such as illustrated in U.S.
Patent No. 3,228,741. These hydrophobic lenses are highly
oxygen p~rmeable but are extremely poor in functional
wettability, deposition resistance and comfort, and also
exhibit a mysterious tight lens syndrome. It is known in
the art to seek to improve the functional wettability of
such lenses by provision of an ultrathin coating of hydro-
philic polymer~ See, e.g., U.S. Patent Nos. 3,854,g82;
3,916,033; 3,925,178; and 4,143,949. Generally these
e~forts have not in any event proven successful. One
reason is because the silicone rubber lens is rather
rigid, and as a consequence an ultrathin (i.e., Angstoms
level) hydrophilic coating is easily rubbed away during
routine cleaning cycles, with the result that the lens
soon re-exhibits the poor wettability, poor deposition
resistance, discomfort and tight lens syndrome character-
istic of sili~one rubber hydrophobic lenses. Provision of
thicker layers of hydrophilic polymer on the lens to
resist rubbing off is impractical, since oxygen permeabi-
lity of the lens is substantially reduced and since the
differences between the refractive index of the silicone
rubber and the thick hydrophilic polymer coating become
such as to xesult in a highly u~desirable lens.
In the present invention, the lens per se is a
hydrophilic SGP lens containing a substantial amount of
water (eOg., generally at least 25% by weisht) such that
its surface, in contrast to the silicone rubber lenses, is
already highly hydrophilic and no apparent need would
exist to provide ~ hydrophilic polymeric surface coating
thereon as is taught with respect to hydrophoblc lens
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~o,~/~2B3 2 ~ 4 ~ ~ 3 9 P~T/U~90/0~032
ma~erials. In the present invention, it has surprisingly
been found that the SGP lenses, even though having highly
hydrophilic surfaces, neverthèless can still be véry poor
in clinical performance, and that this problem can be over~
come by providing on the surface of the SGP lens a ratio
of hydroxy,acrylic units to silicon units which is suffi-
cient to bring about significant clinical improvemént.
~ lso in contrast with the treatment of hydrophobic
silicone rubber lenses, it is found that the criteria
employed in improving wettability o those lenses by hydro-
philic monomer coatings is not correlatable to bringing
about improved clinical perormance in the hydrophilic SGP
lenses to which the present invention is directed. For
example, for hydrophobic lenses, acceptable wettability
has been determined based upon contact angle (see, e.g.,
Col. 7, lines 13-16, of U.S. Pa~ent No. 4,143,949~, result-
ing in findings that coatinys based upon amide monomers
(e.g., ~-vinylpyrrolidone) are quite effec~ive in improv-
ing wettability ~see, e.g., E~ample 1-2 of the above
patent). In contrast, however, in the context of the
hydrophilic SGP lenses of the present invention and parti-
cular those of preferred center thickness of from 0~05 to
O.OB mm, such amide group-containiny monomers are quite
ineffective in improving the clinical performance of the
SGP lenses.
Accordingly, the findings and techni~ues of the
present invention would not have been derivable or pre-
dictable from the known practices regarding improving the
wettability of hydrophobic silicone rubber lenses.
DETAILED DESCRIPTION OF THE INVENTION
The basic teachings and formulations and techniques,
regarding formation of silicone-based SGP lenses are known
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Wo~1/04283 %~ i 9 -6- PCTtU~90/05~32
in the art, as reflected in the earlier-mentioned patents,
the disclosures o~ which are!expxessly incorporated herein
by reference. The SGP lens is formPd from the polymeriza-
tion product of compositions containing at least one poly-
merizable vinylic sîloxane IPVS) monomer, and at least one
hydrophilic vinylic monomer. The polymerizable vinylic
siloxane monomer contains at least one polymerizable
vinylic group such as acrylic, styrenyl or vinylic group,
at least one polysiloxanyl group, and at least one linkage
connecting these two groups; thus, for example: ..
tris(trimethylsiloxy)silylpropyl-glycerol-ethyl
methacrylate
CH3
CH2=CCH3Coo(cH2~2oc~2cHoHcH2o(cHz)3si~os -CH3)3; and
~ -tris(trimethylsiloxy)silylpropyl methacrylate
~also sometimes referred tD hereinafter as TSM)
CH3
CHz=CCH3COO(CH2) 3Si ( osi-c~3 ) 3
CH3
Hydrophilic vinylic monomers suitable for use in
SGP lens compositions along with the PVS include, for
example, N,N dimethylacrylamide (NNDMA), 2-hydroxyethyl
methacrylate (HEMA), glyceryl methacrylate (GMA~, N-vinyl
pyrrolidone and the likeO
The lenses Per se are formed by lathe cutting, cast
molding, spin casting, or other like known techniques.
As earlier noted, SGP lenses made according to the
known formulations possess a high oxygen permeability but
exhibit poor clinical performance. In the present inven-
tion, it has been discovered that by increase of the
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~VO91/~83 P~T/US9~/05032
2t~0419
proportion of hydroxy acrylic monomer ~HAM) units, preEer-
ably HEMA and/or G~A units, to silicon units at the lens
sur~ace, the clinical performance can be substantially
improved. As used herein, the units referred to are the
structural monomeric units or the number of silicon
atoms, including those as par~ o~ an overall copol~mer.ic
structure.
Hydroxy acrylic monomer (HAM) suitable for the
practice of this invention correspond to the formula
H2C - C (: = O
wherein R is H or a substituted or unsubstituted alkyl,
such as methyl or CH2COOH; and X is a radical selected
~rom the group consisting of hydroxyalkyloxy, hydroxy-
alkyl amine, ~nd hydroxy; with the alkyl being
substituted or unsubstituted, and preferably selected
from Cl to C1O alkyls, most preferably C2 and C3
alkyls; and with the hydroxy on the alkyl being either a
single hydroxy (e.g., as in 2-hydroxyethyl methacrylate)
ox multiple hydroxy (e.g., as i~ glyceryl methacrylate ) .
Exemplary and preferred hydroxy acrylic monomers are:
1. 2-hydroxyethyl acxylate or methacrylate;
2. glyceryl acryla~e or methacrylate;
3. ethylene glycolato ethyl acrylate or methacry-
late, i.e., CH2=CRCOO-CH2-CH2-O-CH2-CH2-OH
4. glycerolglyceryl acrylate or methacrylate, i.e.,
CH2=CRCOO-CH2C~(OH)-CH2-O~C~2-CH(OH)-CH2-OH
5. N-hydrox~methyl, N-methyl acrylamide or
methacrylamide;
6. N-2-hydroxyethyl, N-methyl acrylamide or
methacrylamide;
7. N-2,3-dihydroxypropyl, N-me~hyl acrylamide or
- -methacrylamide;--
8. acrylic acid, methacrylic acid or itaconic- -
~-- - acid.~
.
:
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W~91/04~3 PC~/~S90/05032-
-8-
As noted, the SGP lens of the invention is made from
the known SGP lens compositions and, aftex lens formation,
the lens is then treated to provide on its surface a pro-
portion of H~ units to silicon units (e~g., by increase
of HAM units and/or by decrease of silicon units) suffi-
cient to provide improved clinical per~ormance o~ the
lens,-such as functional wettability, deposition resist-
ance, dehydration resistance and comfort.
One means ~or achieving the re~uisite surface
proportion of HAM to silicon units is by reaction of the
lens surface, preferably in the dehydrated state, with a
pol yol of the formula Rl~OH)~ where Rl is a
substituted or unsubstituted alkyl, preferably a C2 to
C5 alkyl, and n is an integer of at least 2, such as
glyceryl methacrylate, ethylene glycol, glycerine,
glycerine-glycerine, polyglycerine, or the like. The
reaction is preferably carried out in the presence of a
base, such ~s sodium hydroxider preferably in a
concentration of 0.1 to 10 mole percent based on the
polyol, or an acid or acid-containing mixture, such as
ethanol/sulfuric acid, the reaction beiny conducted to the
extent that the physical properties of the base lens
(e.gO, strength, oxygen permeability, softness, rebound
elasticity, etc.) are essentially unaffected. This
reaction is intended to increase the HAM units in the
surface layer by transesterification and/or to reduce the
silicon units by the cleavage of siloxane bonds catalyzed
by base or acidO
Alternatively, the core lens can be treated with a
HAM, preferably 2-hydroxye~hyl acrylate or methacrylate,
by grafting, deposition or coating to the lens surface so
as to provide a sufficient proportion of HAM units to
silicon units at the lens surface. The grafting, deposi-
tion or coating can be carried out using known radiation-
induced reactions, including reactions induce~ by W ,
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~ 4283 2 ~ ~ ~ 4 ~ 9 P~T/US9010S03~
_9_
x-ray, ~ -ray, and other electromagnetic radiation, such
as xadio frequency, micrawave and the like, electron beam
radiation, including eleotrical discharge, and the like,
with reactions induced by UV, ~-ray. or electron beam
radiation being preferred. The treating techni~ues per se
that can be ùsed in the practice of this invention are
well known in the art, such as the grafting, deposition or
coating cured by W , ~-ray or electron beam, i~lustrated
in U.S. Patent Nos. 3,916,033 and 3,854,982; coatin~ by
spin casting or cast molding of the lenses cured by radia-
tion; or plasma treating techniques, such as those dis-
closed in U.S. Patent Nos. 3,925,1~8 and 4,143,949, as is
well known in the art. The disclosures of these pxior art
patents are expressly incorporated herein by referenceO
In the preferred embodiment of the invention, the surface
treatment produces on the lens surface a thin coating
consisting essentially of poly(hydroxy alkyl acrylate
and/or methacrylate), more preferably poly~2-hydroxyethyl
acrylate and/or methacrylate).
The re~uired sufficient proportion of HAM units to
silicon units on the lens surface that produces the desir-
able clinic~l performance will vary primarily depending
upon the type and amount of particular PVS and hydrophilic
monomer employed. However, the sufficient proportion in
the surface layer will, at any proportion, be higher than
that existing in the lens body or core. Preferably, the
proportion of HAM units to silicon units in the surface
layer is at least 0.5. Generall~, the higher the propor-
tion the better the clinical perfonmance of the lens, and
the thicker the treated surface layer the better the
durability of the lens wettability. However, the treated
layer can not be so thick that the desired properties of
the lens are adversely affected. The extent of accep~able
surface treatment can be monitored by high resolution
photoelectron spectroscopy ~ESCAj or based on the clinical
response as lllustrated ln the ~amples of this spec fic2-
3, ~_~ ~n, tn~ ~iS~l~s~ ~`~ Ih' ~ ,; ~n~
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WO91/04~g3 æ~ PCT/VS90/05032--
--10--
the sufficient proportion of H~M units to silicon units on
the lens surface can easily be determined by those skilled
in the art.
Although not wishing to be bound by any theory as
such, it is postulated that the improvément in the clini-
cal perormance of ~he lens comes about, at least in part,
by virtue of establishment of compatibility between the
delicate corneal wetting mechanism of the eye and the
composition and structure of the lens surface. The known
SGP lens having insufficient proportion of HAM units to
silicon units or containing too high a level of silicon
units on the surface are too hydropho~ic for the spreading
and binding of mucin to the lens surface. Mucin is the
excellent wetting agent used in the cornea and contains a
certain proportion of hydrophilic sites to hydrophobic
sites. With increasing amount of HAM units on the lens
surface, there are provided increased sites for hydrogen
bonding with the hydrophilic sites on the mucin, while
reduction of silicon surface units provides fewer hydro-
phobic sites and thus better spreading of mucin on the
lens surface. As a consequence of the preferred embodi-
ment of the invention herein, which results in the lens
surface having a sufficient proportion of HAM units to
silicon units, the lens surface becomes more closely
matched to, and receptive to, tear mucin. As a result,
the mucin can better spread on and bind to the lens
surface so as to provide the improved clinical perform-
ance. Thus, when the wet~ing angle of the lens is
controlled to that of the corneal surface free of mucin,
the best results of this inven~ion may resul~.
The invention is further illustrated with reference
to the following examples.
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~0 gltO4283 2 ~ ~ ~ 4 1 9 Pcr/US90,05~32
EXAMPLE 1
SGP lenses were fabricated from buttons which were
made according to the formulations and procedures set
forth in U.S. Patent No. 4,182,822, the starting formu-
lation consisting of 36% (by weight), ~tris~trimethyl-
siloxy) silylpropyl methacryla~e ~TSM) prepared according
to Example 1 of the above patent, 59% N,N-dimethylacryl-
amide ~NNDMA), and 5% methyl me~hacrylate (MMA) with 0.3%
~-~utylperoxypyvalate included as a catalyst. The formu-
lation was placed in a Teflon tube. Aftex deoxygenation
by nitrogen for 15 minutes, the tube was sealed and the
formulation was polymerized in a 40C water bath for six
houxs, followed by a 100C treatment for another six
hours. ~he buttons cut fr~m the rods were post-cured a~
110C under high vacuum (0.5 Torr~ for six hours.
The lens can be made by the lathe technigue known in
the art. The hydrated lenses were extracted and condition-
ed in physiological saline solution for a time sufficient
to insure no substantial irritation.
The lens thus made has high DK, about 4 to 5 times
higher than that of the conventional poly HEMA soft lens,
and contains abou~ 50% by weîght of water, and thu.s has
softness, rebound elasticity and a highly hydrophilic lens
surface. The proportion HAM units to silicon units on the
lens surface is equal to zero. Clinically~ the lenses
were very poor in performance such as functional wettabi-
lity, deposition resistance and comfort, making the lens
unsuitable for extended wear.
Provision of 6% by weight HEMA in the formulation,
such that the formula~ion comprised 36% TSM, 58% NNDMA and
6% HEMA, results in a lens having high DK, softness,
rebound elasticity, a highly. hydrophilic surface and a
.
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WO~l/0~283 ,~ `9 -12- PCT/US90/0;032
proportion of HAM~to silicon units equal to 0.15, and thus
an improved SGP lens having improved clinic 1 performance,
such as functional wett~bility, deposition resistance and
comfort as compared to the control lens above. Clinical-
ly, the lenses could be worn for up to s~veral hours by
test patients.
In the same manner, using 20% by wei~ht HEMA, such
that the lens formulation contains 36% TSM, 44% NNDMA and
20% HEMA, results in a l~ns having high DK, so~tness,
rebound elasticity, a highly hydrophilic surface and a
proportion of HAM units to silicon uni~s e~ual to 0.5, and
thus even more improved clinical performance, such as
functional wettability, deposition resistance and comfort,
as compared to the control lens. Clinically, the lenses
could be worn continuously for up to several days by test
patients, with wettability marginally u~acceptable in
certain circumstances.
Further increase of the H~ to silicon proportion by
increase of the amount of HEMA in the composition is at
the expense of TSM, and thus reduces the oxygen permeabi-
lity of the lens and/or causes the formation of opa~ue
material. As shown in the follswing examples, further
increase of the HAM to silicon proportion can be achieved
by surface treatment.
EXAMPL~ 2
The lens containing 20% HEMA as made in Example 1,
after being hydrated in physiological saline solution, is
then extracted in isopropanol for 24 hours, followed by
treatment in the dry state with glycerine (96% pllri~y,
Colgate Palmolive Co~) containing 1 mole% NaOH at 70C for
30 minutes by stirring. The strength of the lens after
the treatment was not significantly affected. The result-
ing lens could be used for at least weekly extended wear
... . . . . ..
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I/04~83 PCT/US~0/05032
-13-
by the test patients. The clinical of long texm wearing
on one patient showed that the lenses could indeed con-
tinuously be worn for up to 3 months for at least certain
patients. - Thus, the- surface treatment resulted in sub-
stantially improved clinical performance.
- . ,
`EXAMPLE 3
. : .
A SGP lens comprising 47~ IbY weight) TSM, 45% NNDMA
and 3% H~M~, having 38% water content, high DK, softness,
highly hydrophilic lens surface and a proportion of HAM
units to silicon units equal to about 0.15, was found to
be unsuitable ~or extended wear. Clinically, the lens
produced poor vision, discomfort and en~ountered serious
deposition problems within less than four hours of wear.
However, treatment of the same lens in dehydrated state by
stirring the lens in a glycerine reagent (96% purity,
Colgate Palmolive Co.) containins 10 mole% NaOH at 70C
for 2 hours converted the lens to one which on the same
patient could be used for weekly exte~ded wear ~or a three
week testing period with stable vision and no observable
deposition, and demonstrated a liquid layer over the lens
sur~ace.
EXAMPLE 4
According to an independent surface study (about 100
A surface layer) by photoelectron spectroscopy (ESCA)
analysis of the lens after being treated as described in
Example 3 showed that there was ~ reduction of about 18%
silicon or about 30% siloxy group and an increase of over-
all carbon content from 62.5 to 65% in which the C in the
CO group increased from 10.5 to 12.5% and the C in the
COOR group increased from 5.3 to 6~3% after the txeatmen~.
The increase of CO and COOR content should indicate that
the transesterification of glycerine occurs, i.e.,- the
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W~91~04283 ' PCT/US90/~5032
-14-
formation of glyceryl methacrylate. The reduction of
silicon units and/or the increase of glyceryl methacrylate
units after the treatment increases the proportion of HAM
units ~o silicon units which provides the substantially
improved clinical performance as described above. tNote:
ESCA data is the average value of the treated surface with
100 A depth. Thus, the value right at the surface is
substantially higher than ~hose reported above.)
EX~MPLE S
An unhydrated optically polished lens button was
made according to U.S. Patent No. 4,182,822 employing 36%
(by weight) TSM, 42% NNDMA and 22% HEMA, and glycerine
surface treated as set forth in Example 3 herein. The
button was fully hydrated in physiological saline solu-
tion, and its surface was subjected to a number o~
simulated cleaning cycles, each cycle involving thumb-
rubbing 10 times in tap water, followed by wetting in
physiological saline solution. The surface wettability to
the physiological saline solution was substantially the
same based on visual inspection after sixty (60) cleaning
cycles, e~uivalent to about one years service life of the
lens in weekly extended wear.
The surface of the untreated button was substan-
tially not wettable by physiological saline solution under
the same testing condition.
Although the invention has been described in
connection with particular preferred embodiments, it is
not intended to limit the invention to particulax forms
set forth, but on the contrary, it is intended to cover
such alternatives, modifications and equivalents as may be
included within the spirit and scspe of the invention as
defined by the appended claims~
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