Note: Descriptions are shown in the official language in which they were submitted.
~3CP~
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4-15760/~/CGC 1180
Amphoteric surfactant solution for cleanin~ or ~reserving ~oft
contact lens~
The present i.nventlon relates to a 301ution for cleaning or preserv-
ing a soft hydrophilic contsct len~ comprising an amphoteric
surfactant which also serve~ a~ a ~olutlon preservative.
A number of contact len~ cleaner solutions are known ln the art.
Typically 6uch solutions e~ploy either sorbic acid, thimerosal,
chlorhe~idine, a polyquaternary germicide, a synthetic antibiotic or
a conventional quaternary germicide, such a3 benzalkonium chlor~de
aq a preservative agent~ However, these conventional preservatives
have drawback3 that tend to re~trict their use. For example, sorbic
acid characteri~tically contains formaldehyde residues; thimerosal
in some patients acts as an allergy sensitizer, chlorhexidine is
relatively toxic; and benzalkonium chloride, over a period of time,
will tend to accu~ulate in soft hydrophilic contact lens materials
and tend to release to the cornea to cau~e eye irritation.
While U.S. Patent No. 4,046,706 di~close6 the use of certain
amphotaric imidazole surfactants in lenR-cleaning solutions, such
solution~ characteristically also require the presenca of a germ~-
~id81 pre~ervative agent of the type discussed above.
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:~3~
Surprisingly and unexpectantly, it has now been found that, while
the instant amphoteric surfactants contain a quaternary nitrogen,
they do not appreciably build up or accumulate in conventional
hydrophilic soft contact lenees. This i9 in clear contrast to
conventional quaternary germicides, such as benzalkonium chlorid0s
(i.e., alkyl substituted dimethylbenzyl ammonium chloride wherein
alkyl is a mixture of C8 to Cl 8 alkyl moieties), cetylpyridinium
chloride and dodecyl ~rle~hanolamine hydrochloride, which tend to
accumulate in hydrophilic soft contact lens materials. Moreover, the
iDstant amphoteric surfactants do not tend to aocumulate in the eye
and are characteristically less irritating than such conventiona:l
quaternary germicide~.
It is therefore an ob~ect of the present invention of overcoming the
vArlous drawbacks associated wlth the use of prior art soft contact
lens-cleaning solutions.
It i8 a further obJect of the present invention to provide a method
for cleaning and preserving soft hydrophilic contact lenses using an
effectlve surfactant and solution preservative amount of the instant
amphoteric ~urfactants.
It is yet a further object of the present invention to provide
compositions useful in such method3 and their preparation.
The instant invention relates to an aqueous self-preserving soft
contact lens cleaning or preserving solution comprising, as its only
preservative agent, an effective surfactant and solution preservlng
amount of a water-soluble amphoteric s~sfactant of the formula I,
R-A--Rl _ ~ ~4 - C00
~3~
- 3 --
wherein R i8 alkyl, alkenyl or slkanedienyl of 6 to 18 carbon atoms
each of which are unsubstituted or substituted by halo, hydroxy or
amino; A iB -O-, -S-, -C~O~O- or -C(O)NR' where R' iB hydrogen or
lower alkyl; Rl i8 alkylene of 2 to 6 carbon atoms which is unsub-
stituted or substituted by hydroxy; R2 and R3 are independently
hydrogen or lower alkyl, which iB unsubstituted or substituted by
carboxy or by one or two hydroxyls, one of which may be esterified
with pho~phoric or sulfuric acid; and R4 is alky:Lene of up to
3 carbon atoms which is unsubstituted or substituted by hydroxy; or
an ophthalmologically acceptable salt thereof
In case A is -C~O)O- or -C(O)NR'- the carbonyl gro~p thereof is
preferably attached to R.
Alkyl of 6 to 18 carbon atoms has prsferably 8 to 18 carbon atoms
and is e.g. octyl, decyl, undecyl, dodecyl, tridecyl, pentadecyl,
hexadecyl, heptadecyl, octndecyl, or a mlxture thereof.
Alkenyl of 6 to 18 carbon atoms has preferably 8 to 18 carbon atoms
and is e.g. octenyl, decenyl, undecenyl or heptadecenyl, such as
heptadec-8-enyl.
Accordingly, in case A is -C~O)NH-, the partial structure R-A- of
the compounds of formula I is represented e.g. by C11-C17-alkyl-
carbonylamino or Cl7-alkenylcarbonylamino, such as lauroylamino,
myristoylamino, palmitoylam~no, stearoylamino, oleoylamino, or 8
mixture thereof, such as cocoylamino. The latter is even called
cocoamido and is an extract from natural sources with an average
number of 12 carbon atoms.
Halo is e.g. fluoro, iodo, or preferably chloro and bromo.
Lo~er alkyl ha~ e.g. up to 7 carbon atoms, preferably up to 4 carbon
atoms, and is e.g methyl, ethyl, propyl, butyl or tert.-butyl.
~3~
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Alkylene of 2 to 6 carbon atom~ ls e.g. 1,2-ethyle~e, l,3-propylene
or l,4-butylene. These alkylene groups may be substituted by
hydroxy, such that e.g. hydroxypropylene or hydroxybutylene results,
preferably 2-hydroxy-l,3-propylene.
Preferably A is -C(O)NH- and Rl is alkylene of 2 to 3 carbon atoms.
R2 and R3 are preferably independently lower alkyl which i~ unsub-
stituted or mono- or disubstituted with hydroxy, one hydroxy of
which may be esterified with phosphoric acid to form the correspond-
ing mono-, di- or tri-organophospate eYter.
R4 is preferably unsubstituted alkylene of up to 3 carbon atcm~ and,
most preferably, i9 methylene, 112-ethylene, 1,l-ethylens,
1,3 propylene or l,2-propylene. As an alternate preferred embodi-
ment, R4 i9 2-hydro~y~l,3-propylene.
Preferred are solution~ comprising, as their only preservative
sgent, a surfactant of formula I wherein R is alkyl or alkenyl of
ll to 17 carbon atoms, A is -O- or -C(O)NH-, the carbonyl group of
which i9 attached to R, Rl is alkylene of 2 or 3 carbon atoms which
ls unsubstituted or substituted by hydroxy, R2 and R3 are indepen-
dently lower alkyl which is unsubstituted or ~onosubstituted by
carboxy or mono- Dr disubstituted by hydroxy, one hydroxy of which
~ay be esterified with phosphoric acid to form the corresponding
triorganophosphate, and R4 i~ alkylene of up to 3 carbon atoms, or
an ophthalmologlcally acceptable salt thereof.
E6pecially preferred are solutions comprising, as their only
preservative agent, a surfactant of formula I wherein R is alkyl of
ll to 17 carbon atoms or alkenyl of 17 carbon akoms9 A is -C~O)N~-,
the carbonyl group of which i5 attached to R, Rl ls alkylene of
2 or 3 carbon atoms, R2 and R3 are independe~tly lower alkyl whi~h
is un~ubstituted or monosub~tituted by hydroxy which may be
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esterified with phosphoric acid to form the corrcspondlng triorga-
nophosphate, and R4 i~ alkylene of up to 3 carbon atoms, or an
ophthalmologically acceptable salt thereof.
Another group of preferred solutions comprises, as their only
preservative agent, a surfactant of formula I, wherein R is alkyl or
alkenyl of 8 to 12 carbon atoms, A is -C(O)NH-, the carbonyl group
of which is attached to R, R1 is alkylene of 2 or 3 carbon atoms, R2
and R3 are independently lower alkyl, and R4 is alkylene of up to
3 carbon atoms, or an ophthalmologically acceptable salt thereof.
P~eferred compounds of formula I include:
N-lauroylaminopropyl-N,N-dimethyl glycine;
N-cocoylaminopropyl-N,N-dimethyl glycine;
N-lauroylaminopropyl-N-carboxymethyl-N-hydroxyethyl glycine;
N-oleoylaminopropyl-N-carboxymethyl-N-hydroxyethyl glycine;
N-3-dodecyloxy-2-hydroxypropyl-N,N-dimethyl glycine;
N-cocoylaminopropyl-N-hydroxyethyl-3-aminopropionic acld; and
tri-13-~N-cocoylaminoethyl-~-hydroxyethyl-N-carboxymethyl)amino-2-
hydroxy-propanol]phosphate.
Specifically pr~ferred are N-lauroylaminopropyl-N,N-dimethyl
glycine; N-cocoylaminopropyl-N,N-dimethyl glycine and tri-13-(N-
cocoylaminoethyl-N-hydroxyethyl-N-carboxymethyl)amino-2-hydroxy-
propanol]phosphate.
Suitably ophthalmologically acceptable salts are salts formed by the
compounds of formula I e.g. with sodium chloride, potassium
chloride, 30dium phosphate, sodium borate, ~odium bicarbonate,
csrbonic acid, borlc acid, diethanolamine and analogous ino~ganic
and organic a~idg, bases and salts conventionally employed in
lens-care solutions A As the artisan can appreciate, where qalts such
as aodium chloride are employed, the zwitterionic inner salt form
may be in equilibrium with the corresponding double salt form.
~3~
If the solution of the invention hereinbefore or hereinafter 19
defined as comprising a compound of for~ula I or a salt thereof,
thi~ definition i9 understood to includ~ ~olu~ions comprising two or
more compounds of formula I, two or more salts thereof or a mixture
of on~ or more compounds of formula I and one or more of the ~alts
thereof.
A fir~t embodiment, according to this invention are aqueous self-
preserving soft contact lens-cleaning solution~. These may contain~
in addition to the compound of fo}mula I, other con~entional
addltives and adjuvants. For example, suitable self-preserving
cleaning solution~ contain based on the total solution weight:
(a) between about 0.005 and about 2.0 % by weight of a coMpound of
formula I;
(b) between 0 and about 5 % by weight oE a substantial}y nonionic
surfactant;
(c) between 0 and about 5 % by weight of a thickener;
(d) between 0 and about 1 % by weight of a chelating agent;
le) between 0 and about 2 % by weight of a buffer;
(f) between 0 and about 2 % by weight of a water-soluble salt
compatible with ocular tissue, and
(g) the remainder water.
Preferably, the compositions of the instant invention contain
betwee~ about O.Ol and about 0.5 %, most preferably between about
0.02 and about 0.2 % by weight compound of formula I.
When present, each of the optional components (b) through ~f~ are
advantageously pressnt in a minimum amou~t of about 0.01 % by weight
based on total solution weight.
Suitable ~ub~t~ntially nonionic surfactants for use as component (b)
advantageou~ly include those nonionic ~urfactants which are known to
be geDarally compatible with ocular tissue, and include phy~iologi-
~3~
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cally acceptable poly(oxyethylene)-poly(oxypropylene) block copoly-
mers, such as those sold under the trademark PLURONIC~ by Wyandotte
Chemical Corporation. Such copolymers are represented empirically by
the formula;
HO(CH2CH20) (CH(CH3)CH20)b(CH2CH20),H
where a and c are statistically equal, the average molecular weight
ranges between about 2,000 and about 16,000, and the polyoxyethylene
units con~titute between about 10 % and 80 % by weight of the
molecule.
Also 3uitable are polyethoxylated alkylphenols, for example, wherein
the alkyl moiety thereof contains between about 6 and 12 carbon
atoms, and there are between about 3 and about 50 polyoxyethylene
unit~ per molecule, as well as the corresponding alkylated methyleno
bis-phenols which are polyethoxylated, such as that sold under the
nam0 TYLOXAPOL by ~uger Chemical Co.
Al~o suitable are polyethoxylated fatty alcohols, acids, amins3,
e.g. wherein the alkyl moiety thereof contains between 6 and
18 carbon atoms and the molecule contains an average of between
about 3 and about 50 polyoxyethylene units. Preferably, the instant
compo~itions contain between O and about 0.5 % by weight of compo-
nsnt (b).
Suitable thickeners (c) include those conventionally employed in
ophthalmic formulations and include, for example, hydroxyethyl-
cellulose, hydroxypropylcellulose, polyvinylalcohol, polyvinyl-
pyrrolidone, polyethylsneglycol and the like. Preferably, a
thickener iB pre~ent in an 8mount between O % and about 2 % by
weight, more preferably between O % and about 1.5 % by weight.
... .
13~ 33
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Suitable chelating agents (d) include conventional chslatlng agents
such as ethylenediamine tetraacetlc acid (~DTA) and the alkali
metal, e.g. di- and tri-sodium salts (edetates) thereof, and
trihydroxyme~hyl aminomethane. Preferably, the chelating agent is
present in an amount 'oetween 0 and about 0.7 % by weight.
Suitable buffers (e) include alkali metal phosphates, citrates,
borates, tartrates, acetates, carbonates, bicarbonates and the
rorresponding phosphoric acid, cltric acid, boric acld, tartaric
acid, and mixtures thereof. Preferably, buffers are present in an
amount bet~een 0 and about 1 % by weight.
Suitable water soluble salts compatible with ocular tissue (f)
include especially those salts conventionally employed in providing
solutions having a salt content equivalent to up to about 0.9 %
sodium chloride. Preferred salts are alkali metal halide~, sulfates,
nitrates, and phosphate salts, especially sodium chloride, potassium
chlor$de, and mixtures thereof.
A æecond embodiment according to the instant invention relates to
aqueous self-preserving soft contact lens preserving solutlons.
These contain a ~olution preserving amount of the compound of
formula I and a sufficient amount of a water-soluble salt5 compa-
tible with ocular tissue, to provide a solution salt content
equivalent in tonicity to about 0.5 % to about 2 % by weight sodium
chloride.
In this alternate embodiment, it i5 preferred to have a sufficient
amount of salt content to provide a solution salt content equivalent
in tonlcity to between about 0.7 and about 1.8 %, and most prefer-
ably between about 0.7 and about 1.0 %, by weight sodium chloride.
- 9 -
Suitable salts which may be employed iD adjusting the tonicity
include alkali metal halides, sulfates, nitrates, phosphates and the
like~ especlally the sodium and potassium salts thereof and ~ost
preferably 30dium chloride, potassium chloride and mixtures thereof.
The lens preserving and storing solu~long, in accordance with this
embodiment, can generally contain the same additives and adjuvants
in the same ranges set forth above in re3pect to ~he self-preserving
contact lens-cleaning solutions, except that the lens-preserving and
storing solutions advantageously contain a sufficient amount of
component (f) salt to provide a solution salt content equivalent in
tonicity to between about 0.7 and about 1.8 % by weight sodium
chloride.
The instant solutlons are u&eful for cleaning proteinaceous, lipid
and other non-protelnaceous deposits which normally accumulate on
conventional hydrophilic soft rontact lense~. These deposits,
derived from mucus, oil3, cosmetic3, protein from tear fluid, and
the like, unless removed, will tend to accumulate on the lenses
seducing the life of such lenses snd their optical clarity. The
instant composition3 ase highly useful in removing and solubilizing
such depoaits while, at the same tlme, are physiologically tolerable
and ~elf-preserving.
Further, the preferred instant lens-storing and preserving solutions
are additionally advantageous in that the tonicity of such composi-
tiona, coupled with the nonisritating nature of the compounds of
formula I to the eye, and their reduced tendency to accumulate in
80ft hydrophilic contact lens materials, make such compositions
highly advsntageous 89 presQrvative len3 media, from which the lens
can be placed directly into the eye without rinsing with a conven-
tional sallne solution.
~3~ 3
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The composition~ of the instant invention arP preparsd from ma-
terlals known per se. Thus, the compound~ of formula I belong to a
known cla~s of amphoteric surfactant~. The compositions may be
prepared by conventionally mixing the ingredients.
It is a further object cf the invention to provide a method for
cieaning a soft contact lens comprising intimately contacting said
~oft contact lens with an aqueous solution containing an effective
surfactant and solution preserving amount of a water-soluble
amphoteric ~urfactant of the fo}mula I. A convenient method of
cleaning the contact len~e~ according to the instant lnvention, i9
to place the lens ln the palm of the hand, place a few drops of
solution on each lens surface9 and rub the lens ~urfaces with the
forefinger or between the thumb and forefinger, and rlnse with
additional solution.
It iB another ob~ect of the lnvention to psovide a method of
pre~erving a soft contact lens by storing said len~ in an aqueous
solution containing a solution preserving amount of the co~pound
of formula I and a sufficient amount of a water-soluble salt, compa-
tible with ocular ti~sue, to provide a solution salt content
equivalent in tonicity to about 0.5 % to about 2 % by weight ~odium
chloride.
The following examples are for illu~trative purposes and aro not
intended to li~it the scope of the invention. In each instance all
percentages and pasts are by weight unless otherwise specified~
~E3EE~ 0.5 ml of an aqueous ~olution contaln~ng 30 percent by
we~ght N-cocoylaminopropyl-N,N-dimethyl glycine (Monateric~ CAB by
Mona Industrie~, Inc.~ i~ combined with 2.613 g ~odium chloride,
1.25 g ~odi~ tetraborate, 1.75 g boric acid, 1.0 ml tyloxapol,
3.S g hydroxyethyl cellulo~e and 2.5 g di~odium edetate. ~ater
" ~3~5~
-- 11 --
added to a total solution volume of 500 ml with stirring. The
resulting solution iB filter sterili~ed using ultrafiltration to
obtain a solution having a pH of 7.2 and an osmolarity of 304.
Example 2: 0.5 ~1 of an aqueou~ solution contain:Lng ~0 percent by
~eight N-lau~oylaminopropyl-N,N-dimethyl glycine (Monateric~ LMAB~
is combined with 2.685 g sodium chloride, 1.25 g tyloxapol, 3.5 g
hydroxyethyl cellulose, and 2.5 g of disodium edetate. Water is
added to a total solution volume of S00 ml with stirring. The
resulting solution is filter sterilized using ultrafiltration to
obtain a solution having a pH of 7.2 and an osmolarity of 298.
Example 3: 0.5 ml of an aqueous solution containing 30 percent by
weight N-cocoylaminopropyl-N,N-dlmethyl glycine i9 combined with
3.45 g sodium chloride, 0.7 g sodium tetraborate, 2.7 g boric acid
~nd 1.0 g disodium edetate. Water is added to a total solution
volume of 500 ml with nti~ring~ Thc resulting solution i~ filter
sterilized usiDg ultrafiltration to obtain a solution having a pH of
7.2 and an osmolarity of 306,
Example 4: 0.5 ml of an aqueous solution containing 30 percent by
weight N-lauroylaminopropyl-N,N-dimethyl glycine is combined with
3.18 g sodlum chloride, 0.7 g sodium tetraborate, 2.7 g boric acid
and 1.0 g disodium edetate. Water is added to a total solution
volume of 500 ml with stlrring. The resulting solution is f~ltrr
sterili~ed using ultrafiltration to obtain a solution having a pH of
7.21 and an oswolarity of 310.
0.3 g of an aqueou~ solution containing 30 weight percent
of tri-~3-~N-cocoylaminoethyl-N-hydroxyethyl-N-carboxymethyl)amino-
2hydroxypropanol3 phosphate (Monaquat P-TL by Mona Industries~
Inc.) is combined with 0.24 g tris-~hydroxymethyl)aminomethane,
1.0 g boric acid and 0.36 ~ sodium chloride and diluted with
sufficient water to obtain a total solution volume of 100 ml.
~3~S83~
- 12 -
Example 6: 1.5 g of an aqueous solutlon containing 30 percent by
welght N-lauroylaminopropyl-N,N-dimethyl glycine, 2.685 g sodium
chloride, 1.25 g sodium tetraborate, 1.75 g boric acid, 1.0 g
tyloxapol, 3.5 g hydroxyethylcellulose, and 2.5 g disodium edetate
are combined. Sufflcient water is addedd with stirring to obtain a
total solution volume of 500 ml. The pH of the solutlon is 7.43,
which i8 ~djusted with 0.5 N HCl to a pH of 7.23.
Example 7: The procedure of example ~ is repeated and identical
amounts of ingredients are used except that 2.5 g of an aqueous
solution contaiDing 30 percent by weight N-lauroylamlnopropyl-N~N-
dimethyl glycine is employed. Upon dilution to 500 ml ~ith wa~er,
the pH is 7.4 which is adjusted with 0.5 N HCl to a pH of 7.20.
1.5 g of an aqueous solution containing 30 percent by
weight N-lauroylamLnopropyl-N,N-dimethyl glycine, 1 g disodium
edetate, 2.7 g boric acid, 0.70 g sodium borate and 3.15 g ~odiu~
chloride are combined and diluted with sufficient water, with
stirring, to make a total solution volume of 500 ml. The solution
has a pH of 7.22 and an osmolarity of 319.
Exmaple ~: The compositions of examples 6, 7 and 8 are evaluated in
accordance with the modified Draize rabbit eye test (Food, Drug, and
Cosmetic Law Reports 233) in order to access potential irritatlon.
The three solutions are each determined to be "non-irritating" in
this test.
