Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
DISINFECTANT COMPOSITIONS FOR
OPHTHALMIC DEVICES - -
Technical Field
The present inventlon relates to preserving ophthal~
5 mic solutions. More particularly it relates to the use -~
of stabilized chlorine dioxide to preserve ophthalmic -
solutions. The present invention further relates to a ~
composition for disinfecting ophthalmic devices wherein -~ ;
such composltion comprises at least 0.02 weight/volume
percent stabilized chlorine dioxide.
Backqround Art
The use of contact lenses has become widespread as a
replacement for conventional eye glasses because of the
improved vision obtained by the wearer or for aesthetic
reasons. Contact lenses accumulate microorganlsms and
cellular debrls from the eye. Thus, the lenses must be ~ -~
perlodically removed and cleaned to prevent lrrltatlon of
the eye or lnfectlon. Solutlons used ln lens care must
be preserved by some means to lnterdlct lntroduclng
mlcroblal contamlnants onto contact lenses or the eye.
Dlslnfectlng preparations are part of the reglmen lndl-
cated for contact lens care. ` ~'`~r~'r~
Numerous ophthalmlc solutlons have heretofore been ~
used wlth lenses. The composltlon of the ophthalmlc ~ ~`
25 solutlon wlll often be dlctated by the polymerlc `
materlals employed ln the fabrlcatlon of the contact
lens. Because of the chemlcal composltlon of most
ophthalmlc solutions, the contact lenses cleaned and
soaked ln such solutlons must be rlnsed prlor to place-
30 ment ln the wearer~s eye to prevent lrrltatlon of the ~ ;
eye.
U.S. patent Nos. 4,696,811 and 4,689,215 dlsclose ;
the use of stabillzed chlorlne dloxlde for the treatment -
and preventlon of oral dlsease, the reductlon of malodor, `~
as an antl-plaque agent, an antl-glnglvltls and antl-
perlodontltls agent, as well as a denture soak and a
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contact lens soak. That ls, the two before-referenced
patents disclose the use of 0.005 percent to 0.02 percent
stabilized chlorine dioxide in sterilized water as a
contact lens soaking formulation. However, the referen-
ces are void of any teaching or suggestion that stabi-
lized chlorine dioxide can be incorporated into an
aqueous saline ophthalmic solution as a preservative for
such a solution.
Thus, while the prior art compositions (including
lo the compositlon disclosed in U.S. Patent Nos. 4,696,811
and 4,689,215) have found some acceptance, such prior art
Disclosure of the Invention
sroadly, the present invention relates to an aqueous
ophthalmlc solution containing an effective minor amount
of stabllized chlorine dioxide to effectively preserve
the ophthalmic solution. ;
In one aspect the present lnventlon relates to an
aqueous ophthalmlc solutlon comprlslng purlfied water as
a vehlcle, from about 0.0002 to about 0.02 weight/volume
percent stabillzed chlorlne dloxide, and an effectlve
minor amount of an ophthalmically acceptable lnorganic
salt to provlde the ophthalmlc solutlon wlth a tonlclty ;~
value substantlally correspondlng to the tonlcity value
of fluids of an eye. To stablllze the pH of the ophthal~
mlc solutlon, the ophthalmic solutlon also lncludes an
effectlve mlnor amount of a bufferlng agent. To provlde
the ophthalmlc solutlon wlth a pH substantlally corre-
spondlng to the pH of the flulds of the eye, and to ~;~
ellmlnate the rlnslng of the contact lenses prior to the `
lnsertlon of the contact lens lnto the eye, the pH of the
ophthalmlc solutlon can be ad~usted, lf requlred, by
addltlon of an acld or a base so that the ophthalmlc
solutlon has an acceptable physiologlcal pH (l.e. a pH ln
the range of from about 6.8 to about 8).
In yet another aspect the present lnventlon relates
to a dlslnfectant composltlon for ophthalmlc devices
. . . ., , ~ . . - . - . ~ , . .. . .
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wherein the dlsinfectant composition comprises at least - `
0.02 weight/volume percent stabilized chlorine dioxide.
An ob~ect of the present invention is to provide a
preservative for ophthalmic solutions. -`~
Another ob~ect of the present invention, while
achieving the before-stated ob~ect, is to provide an
ophthalmic solution wherein the solution has a pH and
tonicity value substantially corresponding to such values
of the fluids of the human eye.
Another ob~ect of the present invention, while
achieving the before-stated ob~ects, is to provide an
aqueous saline ophthalmic solution having incorporated
therein a preserving agent such that the integrlty of the
saline solution is maintained.
Yet another ob~ect of the present invention, while ~ ;
achieving the before-stated ob~ects, is to provide an `
improved composition useful as a disinfectant for
ophthalmic devlces. ,` ;~ ~`
Other ob~ects, advantages and features of the
20 present invention wlll become apparent from the following ~`
detalled descrlptlon when read in con~unctlon with the
appended clalms.
Modes for CarrYing Out the Inventlon `
The incorporatlon of a preservlng amount of stabl-
25 llzed chlorlne dloxlde lnto an ophthalmlc formulatlon has ~-~
been found to be an effectlve preservatlve for ophthalmlc
formulatlons. The preservlng amount of stablllzed
chlorlne dioxide lncorporated lnto an ophthalmlc formula-
tlon (that ls, to prevent mlcroblal growth ln the formu- ` `i
latlon)~ can vary wldely but wlll generally be an amount
sufflclent to preserve the lntegrlty of the formulatlon.
When lncorporatlng a preservlng amount of stablllzed '
chlorine dloxlde lnto an aqueous ophthalmlc solutlon one ~ ?. ~'~
can malntaln the lenses ln contact wlth the solutlon ;
wlthout any substantlal degradatlon of the lenses. The
cleansed and soaked lenses can be placed dlrectly lnto ~ -
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the wearer~s eye without the addltlonal requlrement of -
rlnsing to remove resldual solution therefrom. Thus,
contamlnatlon of the clean lenses ls substantlally elimi-
nated prior to placement in the wearer~s eye.
Further, an effectlve dlslnfectant can be provided
whlch wlll effectlvely klll mlcroorganlsms whlch may be
present on ophthalmlc devlces. The dlslnfectant com-
prlses at least 0.02 welght/volume percent stablllzed
chlorlne dloxlde as the dlslnfectlng agent. ~`~
The term "stablllzed chlorlne dloxlde" ls well known
in the industry and by those skilled ln the art. U.S.
Patent No. 3, 271, 242 dlscloses a form of stablllzed
chlorlne dioxide and a method for produclng same whlch
can be used as a preservatlve for aqueous ophthalmlc
lS solutlons or as a dlslnfectant for ophthalmic devlces. A
commerclally avallable stabllized chlorine dloxlde whlch
can be utlllzed ln the practlce of the present lnventlon
ls the proprletary stablllzed chlorlne dloxlde of Blo~
Clde Internatlonal, Inc. of Norman, Oklahoma. ~`
The term "aqueous ophthalmlc solutlon" as used
hereln ls to be understood to mean a solutlon contalnlng
sterlllzed water as the vehlcle and havlng at least one
other component, such as an ophthalmlcally acceptable
lnorganlc salt, whlch can be admlnlstered to or placed ln ; `
the eye and whereln the solutlon wlll not possess toxlc
propertles or have a deleterlous affect on the tlssue of
the eye. That ls, such solutlons wlll not cause stlnglng
or dlscomfort, redness or other adverse reactlons to the
eye under normal use condltlons.
The term "ophthalmlcally acceptable lnorganlc salt"
as used hereln ls to be understood to mean any lnorganlc
salt whlch ls capable of provldlng the ophthalmlc ~m
solutlon wlth the deslred tonlclty values and whlch does
not lrrltate or cause damage to the tlssue of the eye.
As prevlously stated, one aspect of the present ~ -
lnventlon resldes ln the use of a preservlng amount of ~ ;~
~, . , . : . - ~ .
i~O~97
- 5 ~
stabilized chlorine dloxide in aqueous ophthalmic
formulations, particularly a saline ophthalmlc solution;
or as an ingredient in the formulation of an aqueous~- -
ophthalmic solution, particularly a saline solutlon. In
5 each instance it has been found that ophthalmlc devlces ;~
contacted with an ophthalmic solution containing a pre-
serving amount of stabilized chlorine dioxide do not have ~; ~
to be rinsed to remove residual solution prior to use. ~.
Simllarly, when such solutlons are employed in the ~;
reglmen of contact lenses, the contact lenses can be
placed in a wearer~s eye, wlthout rlnslng, wlthout lrrl-
tatlon or adverse effects occurrlng to the tlssue of the
eye, and wlthout discomfort. ~ :`
The amount of stablllzed chlorlne dloxlde lncor-
15 porated ln the ophthalmic formulatlon as a preservatlve ;~
can vary wldely provlded that such amount effectlvely
prevents mlcroblal growth ln the formulatlon. Generally,
mlcroblal growth ln the ophthalmlc formulatlon can be
prevented when the amount of stablllzed chlorlne dloxlde
lntroduced lnto the formulatlon ls from about 0.0002 to
about 0.02 welght/volume percent of the solutlon, deslr-
ably from about 0.004 to about 0.01 welght/volume
percent.
In order to lnsure that the aqueous ophthalmlc solu-
tlon contalnlng a preservlng amount of stablllzed
chlorlne dloxlde does not lrrltate one's eye, lt ls
deslrable that the ophthalmlc solutlon have a pH value of ~; `
from about 6.8 to about 8 so that the pH of the ophthal-
mlc solutlon substantlally corresponds to the pH value of ` ;;
30 the flulds ln the eye, or whlch can be tolerated by the ;-
eye wlthout causlng any dlscomfort or lrrltatlon. -,~
To stablllze the ophthalmlc solutlon at the deslred
pH, an effective mlnor amount of a bufferlng agent ls
lncorporated lnto the ophthalmlc solutlon. The effectlve
mlnor amount of bufferlng agent employed to buffer the
ophthalmlc solutlon at a pH of from about 6.8 to about 8
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can vary widely and wlll depend to a large degree on the
partlcular bufferlng agent employed, as well as the
chemlcal composition of the ophthalmic solution. However,
deslrable results have been obtalned when the amount of
buffering agent lncorporated lnto the aqueous ophthalmlc
solution to stablllze the solutlon at the acceptable
physiological pH is from about 0.05 to about
weight/volume percent of the bufferlng agent.
Any sultable buffering agent can be employed which ~- `
10 ls compatlble wlth the other lngredlents of the ophthal- - -
mlc solutlon, and whlch does not have deleterlous or
toxlc propertles whlch could harm the eye. Examples
of sultable bufferlng agents are borlc acld, sodlum `` -~
borate, sodium phosphates (lncludlng mono, dl- and trl- d
15 baslc phosphates, such as sodlum phosphate monobaslc
monohydrate, sodlum phosphate dlbaslc heptahydrate, and `
mlxtures, thereof). It should be noted that any other
sultable bufferlng agent can be employed to stablllze the
pH of the ophthalmlc solutlon so that the ophthalmlc
20 solutlon is provlded wlth an acceptable physlologlcal pH,
and the before-mentloned bufferlng agents are merely - ~-
examples of such bufferlng agents. Further, slnce -
bufferlng agents are well known ln the art no further
examples of such bufferlng agents whlch can be utlllzed
25 ln the ophthalmlc solutlons of the present lnventlon are
not belleved necessary.
When lt ls determlned that the buffered ophthalmlc
solutlon does not have a pH value of from about 6.8 to
about 8, the pH of the aqueous buffered ophthalmlc `;
30 solutlon can be ad~usted by the addltlon of an effectlve -
amount of elther a base or an acld, as the case may be.
Any sultable base or acld can be employed to ad~ust the
pH of the aqueous buffered ophthalmic solutlon which does
not provlde the ophthalmlc solution with toxic or deleter-
35 lous propertles whlch could harm elther ophthalmlc devlces
or the eye. An example of a base whlch can be used to
:., ~ .,,'
0 ~ ~ 97
ad~ust the pH of the aqueous buffered ophthalmlc solution
is 1 N sodlum hydroxide; and an example of an acid which
can be used to ad~ust the pH of the aqueous buffered
ophthalmic solution is 1 N hydrochloric acid.
AS set forth above, the integrity of an ophthalmlc
solutlon can be enhanced by the lncorporated of from
about 0.0002 to about 0.02 welght/volume percent stabl~
lized chlorlne dloxlde. That ls, the presence of stabl-
llzed chlorlne dloxlde ln an ophthalmlc solutlon greatly ;~
enhances the useful or shelf llfe of the ophthalmlc
solution.
When formulating an aqueous ophthalmic solution in ~;
accordance with the present invention, stabilized ~`
chlorine dioxide and an ophthalmically acceptable
15 lnorganlc salt or other sultable tonlcity impartlng agent
are admlxed wlth sterlle water to provlde an ophthalmic
solutlon havlng a tonlclty value substantlally corre- '` ` .'~;:.f.
spondlng to the tonlclty value of fluids of the eye. The ;- ; i
amount of water employed as the vehlcle ln the ophthalmlc ~ -
20 solutlon wlll vary dependlng upon the amount of the -
stablllzed chlorlne dloxlde and the ophthalmlcally
acceptable lnorganlc salt and/or other sultable tonlclty
lmpartlng agent employed ln the formulatlon.
The amount of ophthalmlcally acceptable lnorganlc
25 salt utlllzed can vary wldely provlded that the amount of
the lnorganlc salt employed ls sufflclent to provlde the
ophthalmlc solutlon wlth the deslred tonlclty value. ~`~
Generally the ophthalmlc solutlon wlll have the deslred <
tonlclty value when the amount of ophthalmlcally accept- ~ : `
30 able lnorganlc salt employed ln the formulatlon of the
ophthalmlc solutlon ls from about 0.5 to about 0.9 `
welght/volume percent.
Typlcal of such ophthalmlcally acceptable lnorganlc `
salts are alkall metal chlorldes and alkallne earth metal
35 chlorldes, such as sodlum chlorlde, potasslum chlorlde, ;;
calclum chlorlde and magneslum chlorlde. Because lt ls
2C~09'7
-8- -
desirable that one not have to remove resldual aqueous
ophthalmlc solutlon from the contact lenses after the
soaklng and cleanslng procedure prlor to use, the pH of
the ophthalmlc solutlon should substantlally correspond
with the pH of the flulds of the eye. When lt ls deter~
mined that the pH of the ophthalmic solution ls not
within an acceptable physlological pH, (l~e~ a pH ln the
range of from about 6.8 to about 8), the pH of the
ophthalmic solutlon can be ad~usted by the addltion of a -~
base or acid, such as 1 N hydrochlorlc acld or 1 N sodlum
hydroxlde, so that the solutlon has an acceptable physlo-
loglcal pH.
As previously set forth, the stablllzed chlorlne
dloxlde can also be utlllzed as a dlslnfectlng agent in a
dlslnfectant composltlon. When formulatlng such a dlsln~
fectant composltlon a sultable vehicle, such as steri-
llzed water, ls employed and at least about 0.02
welght/volume percent stablllzed chlorlne dloxlde ls
lncorporated as the dlsinfecting agent. Whlle the amount
of stablllzed chlorlne dloxlde employed as the dlslnfect-
lng agent can vary wldely, deslrable results can be
obtalned when the stablllzed chlorlne dloxlde utlllzed as ;~
the dlslnfectlng agent ls present ln the dlslnfectant
composltlon ln an amount of from about 0.02 to 2.0 ;~
welght/volume percent, deslrably from about 0.04 to about
0.1 welght/volume percent, and more deslrably from about
0.05 to about 0.08 welght/volume percent.
When uslng an aqueous ophthalmlc solutlon contalnlng
stablllzed chlorlne dloxlde for the cleanslng of contact
lenses, the followlng procedure ls suggested. The con-
tact lenses are placed ln an appropriate container con- `
taining an amount of the aqueous saline ophthalmic solu- ~ ;
tlon to substantlally cover the contact lenses. The ~-
contact lenses are malntalned ln contact wlth the
solutlon for a perlod of at least flfteen minutes to
allow the contact lenses to be thoroughly soaked in the ~ ~
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solution. Because of the unlque properties of the
stabilized chlorine dioxlde the contact lenses can be
malntained in the solution for long perlods of tlme, even
days, without degradation of the polymerlc materlals from
5 whlch the contact lenses are fabrlcated. Further, the ,
stablllzed chlorlne dloxlde functlons as a dlslnfectant
for other ophthalmlc devlces such as lens holders and
contalners, lnstruments (i~e~ employed in surgery and
manlpulatlon devlces)~ lmplants and the llke, when the
10 dlslnfectant composltlon contalns the heretofore -~
descrlbed amounts of stablllzed chlorlne dloxlde.
In order to more fully descrlbe the present ~ ~ i
lnvention the followlng examples are set forth, However,
the examples are merely lllustratlve ln purpose and are
not lntended to be llmltlng upon the inventive concept as
set forth in the appended claims. , ;~
EXAMPLE I ~ ~:
A series of experlments were performed to determine ~- `
the antlmlcroblal propertles of a borate buffered sallne `: ~ ~
20 solutlon preserved wlth stablllzed chlorlne dloxlde. The `-
stablllzed chlorlne dloxlde employed was the proprletary
stablllzed chlorlne dloxlde of Blo-Clde Internatlonal, ~~ -
Inc. of Norman, oklahoma. The concentratlon of the ~ `
stablllzed chlorlne dloxlde added to the borate buffered ~ ~;
sallne solutlon was varled.
The borate buffered sallne solutlon had the
followlng composltlon~
IngredlentsPercent (Weight/Volume)
Sodlum Chlorlde USP 0.85 ' -~
30 Borlc Acld NF 0.10 ~ ~;
Purlfled Water USP* To lO0 ml ~ ~;
l t*i Quantlty Sufflclent ~Q.S.) to provlde lO0 ml of
The pH of the buffered solutlon was ad~usted by the
addition of elther hydrochloric acld NF or sodlum
hydroxlde NF so that the pH of the sallne solutlon was i
. . ",,; i -:,
2~ ~09~7 :
-1 0
within the range of from about 7.7 to 7.9. ~ ~
The stabilized chlorlne dioxlde was added to the -
borate buffered saline solutlon ln the followlng concen~
trations: --
Percent (Welght/Volume)
0.005
0.004
0.003
0.002
Each of the above concentratlons of stablllzed
chlorlne dloxlde exhlblted the deslred preservatlve pro-
pertles for the borate buffered sallne solutlon. Fur-
ther, all four concentratlons of the stablllzed chlorine
dloxlde exhlblted good antlmlcroblal actlvlty, wlth the
three hlghest concentratlons achleving total bacterial
kill after 24 hours. Tests lndicated that total kill of
bacterla was achleved by the solution containing 0.002 ;~
weight/volume percent stabilized chlorine dioxide after
seven days. ~ ` "
EXAMPLE II
To compare the preservative efficacy of stabilized
chlorine dloxlde on a borate buffered ophthalmic solu-
tlon, a preserving amount of stabilized chlorine dioxide
havlng a raw materlal age of 54 months was utillzed ln
25 one sample; and a slmilar preservlng amount of stablllzed ,
chlorlne dioxlde havlng a raw materlal age of 2 months
was utllized ln a second sample. Each of the samples of
stabilized chlorlne dioxide was the proprletary stabi-
lized chlorine dioxide of Bio-Cide International, Inc. of
Norman, Oklahoma, under the trademark Purogene. ~o aging
effect was detected between the two samples and their use
as a preser~ative for borate buffered sallne solutlons.
However, the aged stablllzed chlorine dioxide (54 month ~ `
age) possessed a slightly superior activity against the ;
yeast C. albicans.
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-11- ~. ~,`
EXAMPLE III ~-
A preservative efflcacy test was performed on a
borate buffered saline solutlon having a compositlon
similar to that of Example I whereln 0.005 weight/volume -~
percent stabllized chlorine dioxide was added to the
borate buffered solutlon and the resulting mixture stored
for 90 days at 45 degrees Centlgrade. At the end of the
storage period the sample was examlned and lt was
determlned that the stablllzed chlorlne dloxlde was an ;~ ~
10 effectlve preservatlve for a borate buffered sallne solu- '',`"',~!"' ',-'''
tlon. , ., .. ~
EXAMPLE IV --
An experlment was conducted to determlne lf a borate
buffered saline solutlon contalnlng 0.005 welght/volume ~ J
15 percent stablllzed chlorlne dloxlde met the USP. Efflcacy
crlteria for ophthalmics as set forth in the U.S. Pharma-
copeia (USP. XXI, 1985). The stabllized chlorlne dloxlde ~:
employed was the proprletary stablllzed chlorlne dloxlde
of Blo-Clde Internatlonal, Inc. of Norman, Oklahoma. The
20 crlterla for preservatlves requlres that a 99.9% reduc-
tlon of mlcrobes challenge occur wlthln 14 days of con-
tact wlth the product belng tested and that no growth of
yeast and fungl occur.
The borate buffered sallne solutlon contalnlng 0.005
25 welght/volume percent stablllzed chlorlne dloxlde met the
before-mentloned crlterla for preservatlves. However, a
control solutlon of the borate buffered sallne solutlon
whlch dld not contaln the stablllzed chlorlne dloxlde
present dld not meet thls USP Efflcacy crlterla for
30 ophthalmlcs. `~
EXAMPLE V
A 21 day subacute eye toxlclty study ln rabblts was -
conducted uslng a borate buffered sallne solution con- ~ ^
talnlng 0.005 welght/volume percent stablllzed chlorlne ;`
35 dloxlde. The borate buffered sallne solutlon contalnlng - ~
' ::; "-
20~097
-12-
the stabilized chlorine dioxlde had the following
composition:
Ingredients Percent (weight/volume)
Stablllzed Chlorlne Dioxide0.005
5 Sodlum Chlorlde USP 0.85
Borlc Acid NF 0.10
Purlfied Water USP* To 100 ml
1 tl Quantity sufficient (Q.S.) to provide 100 ml
The pH of the above buffered saline solution was -
ad~usted so that the pH of the solution was between 7.7
and 7.9.
The ocular effects of the buffered saline solution
containing 0.005 weight/volume percent stabilized
chlorine dioxide were evaluated in rabbit eyes in con-
~unction with Permalens soft contact lenses. Test eye
lenses were sub~ected to dally cleaning, rinsing, and
overnight soaklng with the borate buffered saline solu-
tion contalnlng stabilized chlorlne dloxide. Control eye
lenses were sub~ected to the same reglmen using preserved
normal saline solution. Lenses were flt dlrectly to the
eye and worn dally for a mlnimum of elght hours for 21
consecutlve days.
Eyes were observed dally for dlscomfort at lens
lnsertlon and for gross ocular reactlons at lens removal.
Sllt lamp blomlcroscopy was performed weekly. Pachometry
and rose bengal stalnlng were performed at the concluslon -~
of the experlment. ~lstopathologlcal evaluatlon was
performed on eyes from three anlmals. No slgnificant ~-
ocular reactions were noted.
The following is a summation of the results of the
experiments set forth above~
A. Discomfort: No ocular dlscomfort was noted
at lens lnsertlon throughout the study.
B. Gross observations: At the time of lens ~;
removal, +l hyperemia was noted in one control
eye on Day 17. No other ocular reactions were
2~ 9~
-13-
noted ~- 3
C. SllP Lamp Examlnations (DaYs 7, 14 and 21): No
ocular reactlons were noted ln any rabblt.
D. Corneal Metabollsm (DaYs 7, 14 and 21): No
test related changes ln corneal metabolism, as - -
measured by corneal thlckness, were noted
throughout the study.
E. CYtotoxlcltY (DaY 21): Rose bengal staining
..
appeared normal ln both eyes of all rabblts,
lndlcatlng that corneal eplthellal cell vltall~
ty was not affected by the solutlon tested.
F. HlstoPatholoqical Evaluation: No mlcroscoplc
changes whlch can be speclflcally related to
the test reglmen were apparent among the eyes ~ -
and extraocular tlssues examlned. There were
no predlctable mlcroscopic dlfferences observed
when comparlng the test eyes and extraocular
tlssues wlth the control eyes and extraocular Q``'"'"~
tlssues. ~ ~
The above data lndlcates that a borate buffered ~ `
sallne solutlon contalnlng 0.005 welght/volume percent
stablllzed chlorlne dloxlde, in con~unctlon wlth
Permalens soft contact lenses, is not discomfortlng, `` ``
lrrltatlng, toxlc or cytotoxlc to rabblt eyes followlng ::
25 21 consecutlve days of testing. ~`~
EXAMPLE VI ~ ~ .,'.'i~''h'~'.
A 1 day acute eye toxicity and cytotoxicity study ln
rabblts was conducted using a borate buffered saline
solution containing 0.005 weight/volume percent stabi- ~-
30 lized chlorine dloxide. The borate buffered saline solu- ~ ,
tion containing the stabilized chlorine dioxide had the
following composition~
Ingredients Percent (weight/volume) -
Stabillzed Chlorlne Dioxide 0.005
35 Sodium Chloride USP 0.85
Boric Acld NF 0.10 ~,
-- ZC~6)97
-14-
Purified Water USP* To 100 ml
* Quantity Sufficient (Q.S.) to provlde 100 ml
solutlon.
The pH of the above buffered saline solution was
ad~usted so that the pH of the solution was between
7.7 and 7.9.
The ocular effects of the buffered saline solution
contalning 0.005 weight/volume percent stablllzed
chlorlne dloxlde were evaluated ln rabbit eyes ln con-
~uctlon wlth Permalens soft contact lenses and multlpletoplcal lnstillatlons. Test eye lenses were sub~ected to
overnight soaking ln the borate buffered saline solution
contalnlng 0.005 weight/volume percent stabillzed
chlorine dloxide followed by direct fit to the eye and 8
hours of wear with topical instillations of the test
solution performed at a rate of one drop every one-half
hour. Eyes were observed for dlscomfort and/or gross `~
ocular reactlons at lens flt, at each lnstlllatlon and at
lens removal. Sllt lamp blomlcroscopy was performed
followlng lens removal. Control eyes were sub~ected to
the same reglmen uslng preserved normal sallne. No
ocular reactlons were noted ln any rabblt.
The followlng is a summatlon of the results of the
experlments set forth above: ~ ;
. :. . i..i~
A. Dlscomfort: No ocular dlscomfort was noted ~ ;"'i~'
at lens flt or at any lnstlllatlon perlod
throughout the study. -
B. Gross Observations: No ocular reactions were
noted at any instillatlon perlod or at lens - i ~
removal. ~ '
C. Slit Lamp Examinations: No ocular reactlons ` ;i
were noted ln any rabblt.
D. CYtotoxlcltY: Rose bengal stalnlng appeared
normal ln both eyes of all rabblts, lndlcatlng ` -
that eplthellal cell vltallty was not affected i ~ ...... -'i ,.,
by the solutlons tested. i:'-"i'','... ';:,
The above data lndlcates that a borate buffered ``~
, .... , .. ,-.......
- 2~ )9~
-15- -
saline solutlon contalnlng 0.005 welght/volume percent
stabllized chlorlne dioxide, in con~unctlon with
Permalens soft contact lenses, is not discomforting,
irritating, toxic or cytotoxic to rabbit eyes following
5 this exaggerated method of testing. ;
EXAMPLE VII
: ,:. .: .
An acute eye toxicity and cytotoxicity study in
rabbits was conducted using a borate buffered saline
solution containing 0.005 weight/volume percent `~
stabilized chlorine dioxide. The borate buffered saline
solution containlng the stabilized chlorine dioxlde had
the following composition: -
Ingredients Percent (Welght/volume)
Stabilized Chlorine Dioxide 0,005
15 Sodium Chloride USP 0.85
soric Acid NF 0.10 ` ~
Purlfied Water USP* To 100 ml `-
l tl Quantlty Sufflclent (Q.S.) to provlde lOO ml " "
The pH of the above buffered sallne solutlon was ,
ad~usted so that the pH of the solutlon was between
7.7 and 7.9. .
The ocular effects of the buffered sallne solutlon i.
,:,,: . :.
contalnlng 0.005 welght/volume percent stabllized
chlorlne dloxide were evaluated in rabbit eyes followlng
l day of multlple topical instillatlons performed at a
rate of one drop every one-half hour for 8 hours. Test i;-
eyes were treated with the borate buffered sallne solu~
tlon contalnlng 0.005 welght/volume percent stabllized ;~
chlorlne dloxlde and control eyes were treated wlth a
preserved normal sallne solutlon.
Eyes were observed for dlscomfort and/or gross
ocular reactlons at each lnstlllatlon. Sllt lamp blo-
mlcroscopy was performed followlng the last lnstlllatlon ~ ari
perlod. No ocular reactions were noted ln the test eyes.
The followlng ls a summatlon of the results of the `
. . . i.. . .
.,.. ~.....
.., ~, ,-, .....
::. ' ', ,:.
. ~ , ~-, .. .. ,. ~ :. .
Z~0~7
-16-
experiments set forth above: -
A. Discomfort: +1 discomfort, lasting up to 30
seconds, was noted in the control eye at 3 of
48 instillations involving two of three
rabbits.
B . Gross observations: No ocular reactions were -~
noted at any instillation period.
C. Sllt Lamp Examinatlons: No ocular reactions were
noted in any rabbit.
D. CYtotoxicitv: Rose bengal staining appeared
normal ln both eyes of all rabbits, lndicatlng
that epithellal cell vltality was not affected
by the preparatlons tested.
The above data lndlcates that a borate buffered .
15 saline solution contalnlng 0.005 weight~volume percent -
stabilized chlorine dioxide is not discomforting, irrita-
tlng, toxlc or cytotoxic to rabbit eyes following this ~ `
exaggerated method of testlng.
From the foregolng descrlptlon and examples, lt ls ,~
clear that the present lnventlon ls well adapted to carry
out the ob~ects and attaln the ends and advantages as
well as those lnherent thereln. Whlle presently pre~
ferred embodlments of the lnventlon have been described
for purposes of thls dlsclosure, numerous changes may be ~ `
25 made whlch wlll readlly suggest themselves to those ,~
skllled ln the art and whlch are encompassed wlthin the ~
splrlt of the lnventlon dlsclosed and as deflned in the ~ ;
appended claims.
"
'~
. ' . ' ' ' ': . ' ! r, ~,
.",., ', . ,',,
,: ... . ....
