Background of the Invention

The present application relates to compositions including effective preservatives, and to methods for disinfecting contact lenses. More particularly, the invention relates to hydrogen peroxide-containing compositions which include a preservative effective after the hydrogen peroxide is destroyed, and to methods for disinfecting a contact lens employing such hydrogen peroxide-containing compositions.

Contact lenses should be periodically cleaned and disinfected by the user to prevent infection or other deleterious effects on ocular health which may be associated with contact lens wear. Currently, there are several different conventional systems and methods which enable the user to clean and disinfect their contact lenses between wearing times. These conventional cleaning and disinfection systems can be divided into "hot" and "cold" systems. Hot systems require the use of heat to disinfect the contact lenses, whereas cold systems use chemical disinfectants at ambient temperatures to disinfect the lenses.

Within the realm of cold disinfection systems are hydrogen peroxide disinfection systems. Disinfecting hydrogen peroxide solutions are effective to kill the bacteria and fungi which may contaminate contact lenses. However, residual hydrogen peroxide on a disinfected contact lens may cause irritation, burning or trauma to the eye unless this hydrogen peroxide is destroyed, i.e., decomposed, neutralized, inactivated or chemically reduced. Therefore, the destruction of the residual hydrogen peroxide in the liquid medium containing the disinfected contact lens is needed to enable safe and comfortable wear of the disinfected contact lens.

An additional concern of hydrogen peroxide contact lens disinfectant systems is to provide adequate preservation for the liquid aqueous medium after all the hydrogen peroxide has been destroyed. Thus, very often the hydrogen peroxide-containing liquid aqueous medium is used very effectively to disinfect the contact lens. After this disinfection, a hydrogen peroxide destroying component, hereinafter referred to as HPDC, for example, catalase and/or a hydrogen peroxide reducing agent, is released into the liquid aqueous medium to destroy all or substantially all the hydrogen peroxide present. At this point, the contact lens may remain in the liquid aqueous medium for up to ten (10) hours or more before being placed back into the user's eye. During this period of time, that is after the hydrogen peroxide is destroyed and before the lens is removed from the liquid aqueous medium, the possibility of recontamination of the contact lens exists. To solve this problem, it is important that the liquid aqueous medium include an effective preservative. Although the preservative can be added to the liquid aqueous medium after the hydrogen peroxide is destroyed, a much more convenient approach is to include the preservative in the hydrogen peroxide-containing liquid aqueous medium.

One problem with this approach that has existed in the past is that hydrogen peroxide itself may act to oxidize or otherwise destroy or inactivate the preservative so that once the hydrogen peroxide is destroyed the preservative is ineffective to preserve the liquid aqueous medium. Also, the preservative should be ophthalmically acceptable so that the disinfected contact lens can be removed from the liquid aqueous medium and placed directly into the eye for safe and comfortable wear.

Glonek et al U.S. Patent 4,914,088 discloses the use of certain phospholipid components for the treatment of dry eye. Shek et al U.S. Patent 4,938,965 discloses the use of phospholipids as prophylactic agents. Phospholipids have been described as being highly surface active, having excellent antimicrobial activity which is retained in the presence of other surfactants and as having unusual mildness to both eyes and skin. In addition, such phospholipids have been indicated as not being adversely affected by solution pH or typical contaminants which commonly deactivate other components.

However, phospholipids have not been suggested for use with contact lenses, or with such media which are exposed to HPDCs to destroy the hydrogen peroxide. In the present context neither hydrogen peroxide nor the HPDC can be considered a contaminant since each is present in a substantial and effective amount.

Summary of the Invention

New compositions useful for disinfecting contact lenses and methods for disinfecting contact lenses employing such compositions have been discovered. The present compositions take advantage of the very effective contact lens disinfectant hydrogen peroxide and the very effective and convenient use of HPDCs to destroy the hydrogen peroxide disinfectant and, at the same time, provide very effectively for the preservation of the liquid media after hydrogen peroxide destruction. The present preservative components are resistant to (or stable in the presence of) effective amounts of hydrogen peroxide and HPDCs, are effective as preservatives of liquid media used to disinfect contact lenses after the hydrogen peroxide disinfectant has been destroyed, and are ophthalmically acceptable so that the lenses can be removed from the liquid media and placed directly in the eye for safe

and comfortable wear. The present compositions can be formed using commercially available components, and used very effectively and conveniently in the practice of contact lens disinfection. The present invention is straightforward, easy to practice and results in substantial and unexpected benefits.

In one broad aspect, the present invention is directed to compositions which comprise water; hydrogen peroxide in an amount effective to disinfect a contact lens contacted with the composition; and a phosphate quaternary component as defined herein, which is preferably ophthalmically acceptable, in an amount effective in preserving the composition after the hydrogen peroxide is destroyed. The phosphate quaternary components have been found to remain stable in the presence of effective disinfecting amounts of hydrogen peroxide so as to be effective in preserving the liquid medium after the hydrogen peroxide is destroyed. In a particularly useful embodiment, the phosphate quaternary component is effective in the present compositions to facilitate the removal of deposit material, for example, proteinaceous deposit material, from contact lenses contacted with such compositions. Thus, the presently useful phosphate quaternary components are preferably effective in combination with hydrogen peroxide to facilitate contact lens cleaning, that is the removal of deposit material from the contact lens.

The present compositions may, and preferably do, further comprise a HPDC in an amount effective to destroy all the hydrogen peroxide present in the composition. The presently useful phosphate quaternary components have been found to be substantially stable in the presence of effective concentrations of such HPDCs. This is an important aspect of the present invention in that not only should the preservative component be stable in the presence of a relatively

high, effective concentration of hydrogen peroxide, this component should also be stable in the presence of an effective amount of the HPDC. Thus, the presently useful phosphate quaternary components are substantially stable in the presence of hydrogen peroxide and in the presence of HPDCs, and remain ophthalmically acceptable and effective in preserving the liquid media containing the disinfected contact lenses after the hydrogen peroxide has been destroyed.

Preferably, the phosphate quaternary component is present in an amount effective to act as the sole preservative of the composition after the hydrogen peroxide is destroyed. The phosphate quaternary component is more preferably the only component of the composition effective to act as a preservative of the composition after the hydrogen peroxide is destroyed. The phosphate quaternary component is often present in an effective bacteriostatic amount and/or an effective fungistatic amount, and is preferably present in an amount less than that effective as a microbicidal or disinfectant component. Thus, the phosphate quaternary components are preferably present in amounts effective to control or maintain the population density of one or more microorganisms, rather than in amounts effective to reduce the population density or eliminate the population of such one or more microorganisms. The present compositions preferably contain the phosphate quaternary component in an amount of about 0.005% (w/v) or less, more preferably less than about 0.005% (w/v) .

In another broad aspect of the present invention, methods for disinfecting contact lenses are provided. These methods comprise contacting a contact lens with the present hydrogen peroxide-phosphate quaternary component-containing compositions at conditions effective to disinfect the contact lens. This

contacting is preferably effective to facilitate the removal of deposit material from the contact lens.

In one embodiment, the methods further comprise contacting the composition with a HPDC in the presence of the disinfected contact lens at conditions effective to destroy all the hydrogen peroxide present in the composition. The composition is effectively preserved after the destruction of all the hydrogen peroxide present in the composition. These and other aspects of the present invention will become apparent in the following detailed description, Examples and claims.

Detailed Description of the Invention The present invention is of value where hydrogen peroxide is used to disinfect lenses which are benefitted by periodical disinfecting. Such lenses, e.g., contact lenses, in particular soft contact lenses, may be made of any suitable material or combination of materials and may have any suitable configuration not substantially deleteriously affected by hydrogen peroxide, the present compositions or the present methods.

The liquid medium used to disinfect a contact lens in the present invention includes an effective disinfecting amount of hydrogen peroxide. Preferably, a disinfecting amount of hydrogen peroxide means such amount as will reduce the microbial burden by one log order in three hours. Still more preferably, the hydrogen peroxide concentration is such that the microbial load is reduced by one log order in one hour. Particularly preferred are those hydrogen peroxide concentrations which reduce the microbial load by one log order in 10 minutes or less. A hydrogen peroxide- containing liquid aqueous medium useful to disinfect contact lenses often has a pH of less than about 5, in particular in the range of about 4 to 5. Aqueous

hydrogen peroxide solutions, preferably containing about 0.5% (w/v) to about 6% (w/v) of hydrogen peroxide, are known to be effective disinfecting solutions for contact lenses. These solutions are effective at killing bacteria and fungi which may be found on contact lenses. However, once a contact lens has been disinfected by being immersed in the hydrogen peroxide-containing liquid medium, the residual hydrogen peroxide should be destroyed so that the lens may be safely and comfortably worn in the eye. If this residual hydrogen peroxide is not destroyed before the lens is worn, irritation to the eye or wearing discomfort may occur.

The present phosphate quaternary components are included in the present hydrogen peroxide-containing compositions in an amount effective in preserving the liquid medium after the hydrogen peroxide is destroyed.

The presently useful phosphate quaternary components, which are preferably ophthalmically acceptable, are stable in compositions containing high and effective concentrations of hydrogen peroxide and concentrations of HPDCs effective to destroy all of the hydrogen peroxide present in the compositions. The presently useful phosphate quaternary components are preferably effective in combination with hydrogen peroxide in facilitating the removal of deposit material from a contact lens.

In general, the phosphate quaternary components include at least one of both a phosphate group and a quaternary nitrogen-containing group. Without wishing to limit the invention to any particular theory of invention, it is believed that this combination of phosphate and quaternary nitrogen-containing groups effectively preserves the liquid medium after hydrogen peroxide destruction and, at the same time, is effective to maintain the phosphate quaternary

component stable prior to its being used as a preservative.

In a preferred embodiment, the phosphate quaternary components useful in the present invention include compounds which have the following general formula

and mixtures thereof. The R group is a tertiary amine radical having at least about 6 carbon atoms, preferably about 6 to about 60 carbon atoms. This carbon atom limitation serves to include materials having significant hydrophobic properties. The R group can be cyclic or non-cyclic, aliphatic, aromatic or heterocyclic. x is an integer from 1 to 3, with x+y equalling 3. M is a cationic component (a shared cation, a cation or cations) having a charge equal to +1, and A is an anionic component (a shared anion, an anion or anions) having a charge equal to -x. In the event that x is 3, the group -(0-M) _y is not present. Both M and A are preferably selected from ophthalmically acceptable ionic components. Examples of cations from which M can be selected include alkali metal ions, alkaline earth metal ions and the like. Examples of anions from which A can be selected include chloride, bromide, iodide, sulfate, bisulfate, nitrate, acetate, maleate fumerate, oxalate, lactate, tartrate, citrate, gluconate, saccharate, p-toluene sulfonate and the like. Chloride is a preferred anion.

In a preferred embodiment, R is an amidoamine moiety of the formula

wherein

R ¹ is selected from alkyl, alkenyl, alkoxy, and hydroxyalkyl having about 5 to about 22 carbon atoms each, and aryl and alkaryl having up to about 20 carbon atoms;

R ² is selected from hydrogen, and alkyl, hydroxyalkyl and alkenyl having up to about 6 carbon atoms each, cycloalkyl having up to about 6 carbon atoms, preferably having about 3 to about 5 carbon atoms, and polyoxyalkylene having up to about 20 carbon atoms, preferably up to about 10 carbon atoms; R ³ and R ⁴ , which may be the same or different, are each independently selected from alkyl, hydroxyalkyl and carboxyalkyl having up to about 6 carbon atoms in each alkyl moiety, and polyoxyalkylene having up to about 20, preferably up to about 10, carbon atoms, provided that R ³ and

R ⁴ taken together with the nitrogen to which they are attached may form a N-heterocycle; and n is an integer in the range of about 2 to about 10.

In addition, R may be an N-heterocyclic radical which may contain one additional hetero atom (for example, oxygen or another nitrogen) and contains 5 or 6 total ring carbon atoms. This heterocyclic radical may be substituted with alkyl and/or hydroxyalkyl having up to about 20 carbon atoms each. Typical of such N-heterocyclic radicals are imidazolinyl, N- alkylmorpholino, alkyl-pyrimidino, alkyloxazolinyl and the like.

Preferably, R is a tertiary amine radical having about 10 to about 40 carbon atoms. More preferred are tertiary amine radicals of the type (C ₆ -C ₂₀ alkyl, dimethyl) amine, such as N,N-dimethyl myristylamine, N,N-dimethyl palmityl amine, N,N-dimethyl laurylamine and the like.

Exemplary tertiary amines include: tributylamine,

(di(hydroxyethyl) ,hexyl) -amine. tripropylamine, triisopropanolamine, bis (2-hydroxyethyl) cocoamine, polyoxyethylene cocoamine, bis (2-hydroxy ethy1) soyamine, polyoxyethylene soyamine, bis (2-hydroxyethyl) tallow amine, polyoxyethylene tallow amine, bis (2-hydroxyethyl)oleylamine, polyoxyethylene oleylamine, bis (2-hydroxyethyl)octadecylamine, polyoxyethylene octadecylamine,

N,N-dimethyl-dodecylamine,

N,N-dimethyl-tetradecylamine,

N,N-dimethyl-hexadecylamine, N,N-dimethyl-octadecylamine,

N,N-dimethyl-cocoamine,

N,N-dimethyl soya amine,

N,N-dimethyl-tallowamine,

N,N-dimethyl-oleylamine, N-methyl-distearylamine, tristearylamine, and

N,N-dimethyl- (hydrogenated tallow)amine

The presently useful phosphate quaternary components may be prepared, for example, by procedures which are known in the art, such as by reacting tertiary amines and phosphate ester halides.

Many of the phosphate quaternary components useful in the present invention can be produced as described in Mayhew et al U.S. Patent 4,503,002, the disclosure of which is incorporated in its entirety herein by reference. A particularly useful phosphate quaternary component is that sold by MONA Industries, Inc. under the trademark Phospholipid PTC. The phosphate quaternary components are present in the present compositions in effective preserving

amounts, preferably in the range of about 0.005% (w/v) or less, more preferably in the range of less than about 0.005 (w/v) . A particularly useful phosphate quaternary component concentration is in the range of about 0.0001% to about 0.005% (w/v) . The specific phosphate quaternary component concentration used depends on a number of factors, for example, the specific phosphate quaternary component employed, the specific application involved and the extent of preservation and/or contact lens cleaning efficacy desired.

An additional advantage of the present invention involves the use of the combination of hydrogen peroxide and the phosphate quaternary component. When this combination is employed in disinfecting a contact lens, the disinfected lens preferably also is cleaner, that is includes less deposit material, for example, proteinaceous deposit material, relative to an identical contact lens disinfected with an identical hydrogen peroxide-containing composition without the phosphate quaternary component. Thus, the presently useful phosphate quaternary components, in effective preserving amounts as described herein, when used in combination with hydrogen peroxide are preferably effective to facilitate the removal of such deposit material from contact lenses. Of course, other contact lens cleaning components, such as the proteolytic enzymes described elsewhere herein, may be used either separate from or in conjunction with the hydrogen peroxide-phosphate quaternary component-containing compositions to provide for more complete removal of the deposit material. However, using a hydrogen peroxide-phosphate quaternary component-containing composition to disinfect the lens preferably results in making these other contact lens cleaning components more effective (more complete removal of deposit material and/or the ability to use reduced amounts of such other cleaning components) and/or in a reduced need for such other cleaning components so that, for

example, contact lens cleaning with such other cleaning components can occur less frequently.

The present compositions preferably further comprise a HPDC which is present in the composition in an amount effective to destroy or cause the destruction of all the hydrogen peroxide present in the composition. In a particularly useful embodiment, the hydrogen peroxide-phosphate quaternary component- containing liquid medium is contacted with the contact lens to be disinfected prior to releasing the HPDC into the composition. For example, the HPDC can be introduced into the liquid medium after the contact lens has been disinfected. Alternately and preferably, the HPDC in a delayed released form can be introduced into the hydrogen peroxide-phosphate quaternary component-containing liquid medium at substantially the same time the contact lens is introduced into this medium. Thus, the present compositions allow for effective contact lens disinfection and, in addition, effectively destroy the residual hydrogen peroxide remaining in the liquid medium so that the disinfected lens can be removed from the liquid medium and placed directly into the eye for safe and comfortable wear.

One important aspect of the present invention is that the presently useful phosphate quaternary components have been found to be stable in the presence of relatively high, effective disinfecting amounts of hydrogen peroxide for long periods of time, for example, during storage and/or transportation of the hydrogen peroxide containing liquid medium. In addition, such phosphate quaternary components have also been found to be stable in the presence of the HPDC used to destroy the residual hydrogen peroxide. After the hydrogen peroxide has been destroyed, the phosphate quaternary component is effective to preserve the liquid medium against recontamination, thus

preserving the contact lens contained in the liquid medium in a disinfected state.

In the event that the HPDC is used in a delayed released form, it is preferably present in the form of a tablet. For example, the HPDC may be present in the form of at least one item, for example, a tablet, which include a coated portion or core, such as a core tablet, and a barrier coating. The barrier coating preferably substantially surrounds the coated portion, which includes the HPDC. The coated portion is preferably about 40% to about 95% by weight of the total HPDC plus barrier coating, while the barrier coating is preferably about 1% to about 60% by weight of the total of the HPDC plus barrier coating. Any suitable HPDC may be included in the present compositions. Such HPDCs should effectively destroy the residual hydrogen peroxide and have no undue detrimental effect on the disinfected lens or on the eye into which the disinfected lens is placed. Among the useful HPDCs are hydrogen peroxide reducing agents, peroxidases (meaning to include therein catalase) and mixtures thereof.

Examples of the hydrogen peroxide reducing agents which are useful in the present invention are alkali metal, in particular sodium, thiosulfates; thiourea; alkali metal, in particular sodium, sulfites; thioglycerol; N-acetylcysteine; alkali metal, in particular sodium, formiates; ascorbic acid; isoascorbic acid; glyoxylic acid; mixtures thereof and the like. A particularly useful peroxidase is catalase. The peroxidases, and especially catalase, are very beneficial in the present invention since such HPDCs are effective to substantially eliminate hydrogen peroxide from a liquid medium in a reasonable period of time, e.g., on the order of about 1 minute to about 12 hours, preferably about 5 minutes to about 1 hour, after the HPDC is initially released into the HPLM.

The present compositions are preferably formulated and structured to provide for the release of the HPDC into the hydrogen peroxide-phosphate quaternary component-containing liquid medium to be delayed for a time sufficient to allow the hydrogen peroxide to effectively disinfect a contact lens, and then to release the HPDC into the liquid medium for rapid and predictable destruction of the residual hydrogen peroxide. The amount of HPDC employed is preferably sufficient to destroy all the hydrogen peroxide present in the hydrogen peroxide-phosphate quaternary component-containing liquid medium into which the HPDC is placed. Excess HPDC may be employed. Very large excesses of HPDC are to be avoided since the HPDC itself may cause problems with the disinfected contact lens and/or the ability to safely and comfortably wear such disinfected contact lens. When catalase is employed as a HPDC, it is preferably present in an amount of about 100 to about 250, more preferably about

150 to about 200 units of catalase ac ivity/percent

(w/v) of hydrogen peroxide in the liquid medium per ml of the liquid medium. For example, an especially useful amount of catalase for use in an aqueous solution containing about 3% (w/v) hydrogen peroxide is about 520 units of catalase activity/ml of solution.

The HPDC may be combined with one or more other components, e.g., in the core of a layered tablet. Such other components may include, for example, fillers, binders, tonicity agents, contact lens conditioning/wetting agents, buffering agents, lubricating agents and the like. Each of these components may be present, if at all, in an amount effective to perform its designated function or functions. The present coated core preferably includes at least one buffering agent. Examples of each of these types of components are conventional and well

known in the art. Therefore, a detailed description of such components is not presented here. An illustrative HPDC-containing core may have the following composition:

Wt.%

HPDC 1-30

Filler 15-90

Tonicity Agent 1-90

Buffer 1-50

Lubricating Agent 0-30

Useful buffering agents include, but are not limited to, acetate buffers, citrate buffers, phosphate buffers and borate buffers. In a particularly useful embodiment, the HPDC is combined with at least one enzyme effective to remove debris from a contact lens. Among the types of debris that form on contact lens during normal use are protein-based debris, mucin-based debris, lipid-based debris and carbohydrate-based debris. One or more types of debris may be present on a single contact lens.

The enzyme employed may be selected from peroxide- active enzymes which are conventionally employed in the enzymatic cleaning of contact lenses. For example, many of the enzymes disclosed in Huth et al U.S. Patent RE 32,672 and Karageozian et al U.S. Patent 3,910,296 are useful in the present invention. Each of these patents is incorporated in its entirety by reference herein. Among the useful enzymes are those selected from proteolytic enzymes, lipases and mixtures thereof.

Preferred proteolytic enzymes are those which are substantially free of sulfhydryl groups or disulfide bonds, whose presence may react with the active oxygen in the liquid medium to the detriment of the activity of the enzyme. Metallo-proteases, those enzymes which

contain a divalent metal ion such as calcium, magnesium or zinc bound to the protein, may also be used.

A more preferred group of proteolytic enzymes are the serine proteases, particularly those derived from Bacillus and Streptomvces bacteria and Asperαillus molds. Within this grouping, the still more preferred enzymes are the derived alkaline proteases generically called subtilisin enzymes. Reference is made to Deayl, L., Moser, P.W. and Wildi. B.S., "Proteases of the Genus Bacillus. II Alkaline Proteases", Biotechnology and Bioengineering, Vol. XII, pp 213-249 (1970) and Keay, L. and Moser, P.W., "Differentiation of Alkaline Proteases from Bacillus Species" Biochemical and Biophysical Research Comm. , Vol 34, No. 5, pp 600-604, (1969) .

The subtilisin enzymes are broken down into two sub-classes, subtilisin A and subtilisin B. In the subtilisin A grouping are enzymes derived from such species are B. subtilis, B. licheniformis and EL. pumilis. Organisms in this sub-class produce little or no neutral protease or amylase. The subtilisin B sub¬ class is made up of enzymes from such organisms as B. subtilis, B subtilis var. amylosacchariticus, B. amyloliαuefaciens and B. subtilis NRRL B3411. These organisms produce neutral proteases and amylases on a level about comparable to their alkaline protease production. One or more enzymes from the subtilisin A sub-class are particularly useful.

In addition other preferred enzymes are, for example, pancreatin, trypsin, collagenase, keratinase, carboxylase, aminopeptidase, elastase, and aspergillo- peptidase A and B, pronase E (from S. σriseus) and dispase (from Bacillus polvmvxa) .

An effective amount of enzyme is to be used in the practice of this invention. Such amount will be that amount which effects removal in a reasonable time (for example overnight) of substantially all of at least one

type of debris from a lens due to normal wear. This standard is stated with reference to contact lens wearers with a history of normal pattern of lens debris accretion, not the very small group who may at one time or another have a significantly increased rate of debris accretion such that cleaning is recommended every day, or every two or three days.

The amount of enzyme required to make an effective cleaner will depend on several factors, including the inherent activity of the enzyme, and the extent of its interaction with the hydrogen peroxide present.

As a basic yardstick, the working solution should contain sufficient enzyme to provide about 0.001 to about 3 Anson units of activity, preferably about 0.01 to about 1 Anson units, per single lens treatment. Higher or lower amounts may be used.

Enzyme activity is pH dependent, so for any given enzyme, there is a particular pH range in which that enzyme will function best. The determination of such range can readily be done by known techniques.

The presently useful phosphate quaternary components have been found to be stable in the presence of effective amounts of such cleaning enzymes. Thus, a contact lens can be both disinfected with hydrogen peroxide and cleaned with such cleaning enzymes while the phosphate quaternary component remains stable and effective to preserve the liquid medium after the hydrogen peroxide is destroyed.

Tablets, pills, granules or the like which release their ingredients in a sequential, time delayed manner are well known and can be produced using conventional technology. Therefore, a detailed description of such items and such production technology is not presented here. However, such tablets, pills, granules or the like are preferably designed to allow one component sufficient time to perform its function before releasing another component which may interfere with

the functioning of the first component. For example, if the item contains a HPDC, the item is preferably designed to allow the hydrogen peroxide in the liquid medium sufficient time to disinfect. Such sufficient time is preferably in the range of about 1 minute to about 2 hours, more preferably about 5 minutes to about 1 hour.

Although multi-layered (including core and coating layers) tablets or pills are preferred, the delayed release form of the present compositions can be present in any other suitable item or items, such as masses of powders, granules and the like. Delayed release technology is well known in the art as exemplified by the text Controlled Drug Delivery, 2nd Ed., Joseph R. Robinson & Vincent H.L. Lee, Eds., Marcel Dekker, Inc., New York, 1987.

Any suitable delayed release component or combination of delayed release components may be employed, provided that such component or components function as described herein and have no substantial detrimental effect on the other components present, on the lens being treated and on the human wearing the treated lens. The delayed release component is preferably at least partially, more preferably completely, water soluble. The delayed release component preferably comprises a major amount of at least one polymeric material. Examples of useful delayed release components include, but are not limited to, soluble cellulose ethers such as methylcellulose, m e t h y l h y d r o x y p r o p y l c e l l u l o s e , methylhydroxyethylcellulose, hydroxypropylcellulose, hydroxyethyl cel lulose and sodium carboxymethylcelluloses; cellulose esters such as cellulose acetate phthalate and hydroxypropylmethyl- cellulose phthalate; polymers derived from at least one of acrylic acid, acrylic acid esters, methacrylic acid and methacrylic acid esters such as methacrylic acid-

methyl methacrylate copolymer (for example that sold by Rohm Pharma under the trademark Eudragit L 100) and methacrylic acid-ethyl acrylate copolymers (for example that sold by Rohm Pharma under the trademark Eudragit L 30D) ; polymers derived from methyl vinyl ether and maleic acid anhydride; polyvinylpyrrolidone; polyvinyl alcohols and the like and mixtures thereof.

The present methods of disinfecting a contact lens include contacting the lens to be disinfected with a hydrogen peroxide-phosphate quaternary component- containing liquid medium at effective contact lens disinfecting conditions. This hydrogen peroxide- phosphate quaternary component-containing liquid medium is preferably contacted with a composition which includes a coated portion containing at least one HPDC and a barrier coating, such as described herein. Using these methods, the lens is disinfected and the residual hydrogen peroxide in the liquid medium is effectively destroyed. Thus, after the HPDC has been released into the hydrogen peroxide-phosphate quaternary component- containing liquid medium and acts to effectively destroy the residual hydrogen peroxide, the lens can be safely and comfortably taken directly from the liquid medium in which it was disinfected. In addition, after the hydrogen peroxide has been destroyed, the phosphate quaternary component is effective to preserve the liquid medium so that the disinfected lens can be kept in the liquid medium for a period of time, for example, up to about 24 hours or about 48 hours or longer without being recontaminated. Further, the phosphate quaternary component is sufficiently ophthalmically acceptable so that the contact lens from the liquid medium can be placed directly in the eye for safe and comfortable wear. In the event that a debris removing enzyme is employed, the contact lens in the liquid medium is also effectively cleaned of any debris. This cleaning

action can occur either at the time the lens is being disinfected, for example, if the enzyme is released into the hydrogen peroxide-phosphate quaternary component-containing liquid medium when the composition is initially contacted with the liquid medium or shortly thereafter; or after the lens is disinfected, for example, if the enzyme is released into the hydrogen peroxide-phosphate quaternary component- containing when the HPDC is released into the liquid medium or thereafter.

It is preferred that the HPDC not be released into the hydrogen peroxide-phosphate quaternary component- containing liquid medium until the lens has been immersed in the hydrogen peroxide-phosphate quaternary component-containing liquid medium for a time sufficient to effectively disinfect the lens. It is also preferred that substantially all of the residual hydrogen peroxide in the liquid medium be destroyed in less than about 3 hours, more preferably in less than about 1 hour and still more preferably in less than about 30 minutes, after the HPDC is initially released into the hydrogen peroxide-phosphate quaternary component-containing liquid medium.

The disinfecting contacting preferably occurs at a temperature to maintain the liquid medium substantially liquid. It is preferred that the contacting temperature be in the range of about 0°C to about 100°C, and more preferably in the range of about 10°C to about 60°C and still more preferably in the range of about 15°C to about 30°C. Contacting at or about ambient temperature is very convenient and useful. The contacting preferably occurs at or about atmospheric pressure. The contacting preferably occurs for a time to substantially completely disinfect the lens being treated.

The following non-limiting examples illustrate certain aspects of the present invention.

EXAMPLES 1 AND 2 A commercial product sold by MONA Industries, Inc. under the trademark Phospholipid PTC was selected for testing. This phospholipid product was a water solution containing about 47% by weight of cocamidopropyl PG-dimonium chloride phosphate indicated as having the following formula:

— — )Na) _v + xCL

wherein R ^a is cocamidopropyl, and x plus y is 3.

A 3% (w/v) aqueous solution of hydrogen peroxide, sold by Allergan, Inc. under the trademark Oxysept I ^® , was treated with the above-noted phospholipid product so that the final concentration of the phospholipid product was 0.005% (w/v) . A quantity, 7.5 ml of this solution was than contacted with a tablet containing catalase coated with hydroxypropylmethyl cellulose and sold by Allergan, Inc. under the trademark Ultracare ^® to destroy the hydrogen peroxide present. The resulting material was then inoculated with four (4) known indicator microorganisms at low levels.

A second quantity of the above-noted hydrogen peroxide-containing solution without the phospholipid product was contacted with a catalase tablet as described above. Thereafter, the resulting material was inoculated with the same group of microorganisms at the same low levels. Both sets of solutions were incubated for seven (7) days and than observed for the growth of the indicator organisms.

Results of these observations were as follows: Three of the microorganisms, Staphylococcus aureas. Aspergillus niger and Candida albicans, did not grow in the material including the phospholipid product. Only

the microorganism Pseudomonas aeruginosa grew in this material. On the other hand, all of the microorganisms grew in the material which did not contain the phospholipid product.

EXAMPLE 3 An aqueous solution containing 3% (w/v) of hydrogen peroxide and 0.005% (w/v) of the phospholipid product identified in Examples 1 and 2 is prepared. 7.5ml of this aqueous solution is placed in a contact lens vial. A contact lens is introduced into the vial and is immersed in the solution. At the same time a coated catalase tablet, such as the tablet identified in Examples 1 and 2, is also introduced in the vial. This procedure results in the contact lens being disinfected and, after one (1) hour, all the hydrogen peroxide in the vial being destroyed. The lens is maintained in the vial immersed in the liquid overnight, that is about ten (10) hours. After this time, the lens is removed from the vial and placed directly into the wearer's eye for safe and comfortable wear. Alternatively, the lens is removed from the vial, rinsed with a buffered saline solution and placed in the wearer's eye for safe and comfortable wear. The lens is found to be disinfected. In addition, the lens is found to be somewhat cleaner, that is the lens has somewhat less deposit material on it, relative to the lens prior to being immersed in the solution. It is found that the phospholipid product identified above effectively preserves the liquid after hydrogen peroxide destruction so that the disinfected contact lens is not recontaminated prior to being placed in the wearer's eye.

EXAMPLE 4

A coated tablet as in Examples 1 and 2 is prepared except that sufficient subtilisin A is included in the

core tablet to provide the core tablet with about 0.4 mg of this enzyme.

Example 3 is repeated except that this enzyme containing tablet is used in place of the tablet noted in Example 3. 10 hours after the contact lens is first introduced into the solution, it is removed from the solution, rinsed with physiological saline solution to remove the subtilisin A and placed into the wearer's eye. It is found that after 10 hours, the contact lens is effectively disinfected and cleaned of protein-based debris. The lens wearer experiences no discomfort or eye irritation from wearing the disinfected and cleaned contact lens. It is found that the phospholipid product identified above effectively preserves the liquid after hydrogen peroxide destruction so that the disinfected contact lens is not recontaminated prior to being placed in the wearer's eye.

EXAMPLE 5 A coated tablet as in Examples 1 and 2 is prepared, and is further spray coated with an aqueous mixture of polyvinylpyrrolidone, sodium carbonate and subtilisin A. The spray coated tablet is dried. The amount of subtilisin A is sufficient to provide the tablet with about 0.4 mg of this enzyme.

This enzyme-containing tablet is used in disinfecting and cleaning a protein-based laden soft contact lens substantially as described in Example 4. 10 hours after the contact lens is first introduced into the solution, it is removed from the solution, rinsed with physiological saline solution to remove the subtilisin A and placed into the wearer's eye. It is found that after 10 hours, the contact lens is effectively disinfected and cleaned of protein-based debris. The lens wearer experiences no discomfort or eye irritation from wearing this disinfected and cleaned contact lens. It is found that he phospholipid

product identified above effectively preserves the liquid after hydrogen peroxide destruction so that the disinfected contact lens is not recontaminated prior to being placed in its wearer's eye. While this invention has been described with respect to various specific examples and embodiments, it is to be understood that the invention is not limited thereto and that it can be variously practiced within the scope of the following claims.