CA2004097A1 - Disinfectant compositions for ophthalmic devices - Google Patents
Disinfectant compositions for ophthalmic devicesInfo
- Publication number
- CA2004097A1 CA2004097A1 CA 2004097 CA2004097A CA2004097A1 CA 2004097 A1 CA2004097 A1 CA 2004097A1 CA 2004097 CA2004097 CA 2004097 CA 2004097 A CA2004097 A CA 2004097A CA 2004097 A1 CA2004097 A1 CA 2004097A1
- Authority
- CA
- Canada
- Prior art keywords
- solutlon
- volume percent
- ophthalmlc
- chlorine dioxide
- chlorlne
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
- A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
- A61L12/10—Halogens or compounds thereof
- A61L12/102—Chlorine dioxide (ClO2)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/40—Peroxides
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- Inorganic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Agronomy & Crop Science (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A disinfectant composition for ophthalmic devices is provided which comprises at least about 0.02 weight/volume percent stabilized chlorine dioxide.
A disinfectant composition for ophthalmic devices is provided which comprises at least about 0.02 weight/volume percent stabilized chlorine dioxide.
Description
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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X(30~097 : ~
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 :.'',' ~'.':',''~.','''''' '.~ ' ` ' ', ' '':
'~: .' .. ' ',' ' ::
X(30~097 : ~
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 . . . ., , ~ . . - . - . ~ , . .. . .
- . ~ ~ . -- :
~ . - .. .
2~0~097 ~ ~ ~
.' ;' ~'' ~ '"' 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 ~ -" .,: .. . .
~`' '.;~'''~'',"
Z(~O~iO97 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 ' ~'.-';"''"'.''' ',.
.:, ''';' - ZO~ )9~
-6- ~
~ ~ .
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 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 ~ ~
'. - .,`", ~:.' ~ ::
" '` ' ' ~ ' `' '' '`'' - ZC0~097 ~
g 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 :
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.
~:, . :::
~ ~. ' ,;': ' ,., ... :. . ,, :: ~
~ 2~0~097 -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 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~
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 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~
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 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, ~, .",., ', . ,',, ,: ... . ....
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 . . . ., , ~ . . - . - . ~ , . .. . .
- . ~ ~ . -- :
~ . - .. .
2~0~097 ~ ~ ~
.' ;' ~'' ~ '"' 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 ~ -" .,: .. . .
~`' '.;~'''~'',"
Z(~O~iO97 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 ' ~'.-';"''"'.''' ',.
.:, ''';' - ZO~ )9~
-6- ~
~ ~ .
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 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 ~ ~
'. - .,`", ~:.' ~ ::
" '` ' ' ~ ' `' '' '`'' - ZC0~097 ~
g 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 :
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.
~:, . :::
~ ~. ' ,;': ' ,., ... :. . ,, :: ~
~ 2~0~097 -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 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~
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 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~
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 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, ~, .",., ', . ,',, ,: ... . ....
Claims (10)
1. A disinfectant composition for ophthalmic devices containing at least 0.02 weight/volume percent stabilized chlorine dioxide as a disinfecting agent.
2. The disinfectant composition of Claim 1 wherein the stabilized chlorine dioxide is present in an amount of from about 0.02 to about 2.0 weight/volume percent.
3. The disinfectant composition of Claim 1 wherein the stabilized chlorine dioxide is present in an amount of from about 0.04 to about 0.1 weight/volume percent.
4. The disinfectant composition of Claim 1 wherein the stabilized chlorine dioxide is present in an amount of from about 0.05 to about 0.08 weight/volume percent.
5. An aqueous disinfectant composition for ophthal-mic devices comprises sterile water as a vehicle and con-taining at least 0.02 weight/volume percent stabilized chlorine dioxide.
6. The aqueous disinfectant composition of Claim 5 wherein the stabilized chlorine dioxide is present in the composition in an amount of from about 0.02 to about 2.0 weight/volume percent.
7. The aqueous disinfectant composition of Claim 6 wherein the stabilized chlorine dioxide is present in the composition in an amount of from about 0.04 to about 0.1 weight/volume percent.
8. The aqueous disinfectant composition of Claim 7 wherein the stabilized chlorine dioxide is present in the composition in an amount of from about 0.05 to about 0.08 weight/volume percent.
9. A disinfecting agent for incorporation into an aqueous composition, the disinfecting agent comprising stabilized chlorine dioxide the stabilized chlorine dioxide being present in the aqueous composition in an amount of at least 0.02 weight/volume percent.
10. The disinfecting agent of Claim 9 wherein the stabilized chlorine dioxide is present in an amount of from about 0.02 to about 2.0 weight/volume percent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27779088A | 1988-11-29 | 1988-11-29 | |
| US277,790 | 1988-11-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2004097A1 true CA2004097A1 (en) | 1990-05-29 |
Family
ID=23062358
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2004097 Abandoned CA2004097A1 (en) | 1988-11-29 | 1989-11-28 | Disinfectant compositions for ophthalmic devices |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU4658089A (en) |
| CA (1) | CA2004097A1 (en) |
| WO (1) | WO1990006126A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8343949B2 (en) | 2004-06-09 | 2013-01-01 | Allergan, Inc. | Stabilized compositions comprising a therapeutically active agent, and an oxidizing preservative |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5324447A (en) * | 1989-10-02 | 1994-06-28 | Allergan, Inc. | Method and activator compositions to disinfect lenses |
| US5078908A (en) * | 1989-10-02 | 1992-01-07 | Allergan, Inc. | Methods for generating chlorine dioxide and compositions for disinfecting |
| US5338480A (en) * | 1989-10-02 | 1994-08-16 | Allegan, Inc. | Compositions and methods to clean contact lenses |
| US4997626A (en) * | 1990-01-05 | 1991-03-05 | Allergan, Inc. | Methods to disinfect contact lenses |
| US5736165A (en) * | 1993-05-25 | 1998-04-07 | Allergan | In-the-eye use of chlorine dioxide-containing compositions |
| US5648074A (en) * | 1993-05-25 | 1997-07-15 | Allergan | Compositions and methods for disinfecting contact lenses and reducing proteinaceous deposit formation |
| WO2010009064A2 (en) * | 2008-07-15 | 2010-01-21 | Basf Corporation | Non-cytotoxic chlorine dioxide fluids |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4654208A (en) * | 1983-03-01 | 1987-03-31 | Stockel Richard F | Anti-microbial compositions comprising an aqueous solution of a germicidal polymeric nitrogen compound and a potentiating oxidizing agent |
| US4689215A (en) * | 1984-07-30 | 1987-08-25 | Ratcliff Perry A | Method and composition for prevention and treatment of oral disease |
| US4696811A (en) * | 1984-07-30 | 1987-09-29 | Ratcliff Perry A | Method and composition for prevention and treatment of oral disease |
-
1989
- 1989-11-22 AU AU46580/89A patent/AU4658089A/en not_active Abandoned
- 1989-11-22 WO PCT/US1989/005292 patent/WO1990006126A1/en unknown
- 1989-11-28 CA CA 2004097 patent/CA2004097A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8343949B2 (en) | 2004-06-09 | 2013-01-01 | Allergan, Inc. | Stabilized compositions comprising a therapeutically active agent, and an oxidizing preservative |
| US8691802B2 (en) | 2004-06-09 | 2014-04-08 | Allergan, Inc. | Stabilized compositions comprising a therapeutically active agent and an oxidizing preservative |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1990006126A1 (en) | 1990-06-14 |
| AU4658089A (en) | 1990-06-26 |
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