IE910646A1 - Hydrogen peroxide destroying compositions and methods of¹using same - Google Patents

Abstract

A composition and method of using such compositions to destroy hydrogen peroxide in a liquid aqueous medium, such as that used to disinfect contact lenses, are disclosed. The composition comprises a coated core containing at least one hydrogen peroxide destroying component effective when released into a liquid aqueous medium to destroy or cause the destruction of hydrogen peroxide present in the liquid aqueous medium, and a barrier coating acting to substantially prevent the release of the hydrogen peroxide destroying component for a period of time after the composition is initially contacted with a hydrogen peroxide-containing liquid aqueous medium. The barrier coating includes material capable of at least partially dissolving in an aqueous medium having a pH in the range of 5.1 to 6.9 by forming one or more soluble salts of the material.

Description

HYDROGEN PEROXIDE DESTROYING COMPOSITIONS AND METHODS OF USING SAME BACKGROUND OF THE INVENTION This invention relates to hydrogen peroxide destroying compositions, and the use of same, to decrease the concentration of, or even substantially eliminate, hydrogen peroxide present in a liquid medium. More particularly, the invention relates to such compositions which are useful in destroying residual hydrogen peroxide present in a liquid aqueous medium containing a contact lens which has been disinfected by the action of hydrogen peroxide.

Contact lenses should be periodically cleaned and LO 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.

Associated with the problem of hydrogen peroxide destruction in contact lens disinfection systems are the problems of easy use and user compliance. To enhance user compliance and ease of use, several efforts have focused on one-step disinfection and hydrogen peroxide destruction. In this regard, various time release tablets containing a core tablet and a soluble or insoluble coating have been suggested.

Kruse et al U.S. Patent 4,767,559 discloses a onestep contact lens cleaning and disinfecting tablet. A core containing a hydrogen peroxide reducing agent and a catalyst is provided. Preferably but not essentially, a thin lacquer polymeric coating, e.g., of acrylic resin (derived from an aqueous, neutral-adjusted solution of a copolymer based upon polyacrylic acid and polyacrylic acid esters), may be sprayed on the core tablet to form an enveloped core tablet. A nonpolymeric jacket mixture containing a hydrogen peroxide generating component is dry coated onto the enveloped core tablet. In this case, the jacket mixture dissolves to form hydrogen peroxide to disinfect the contact lens.

Subsequently, the thin lacquer polymeric coating enveloping the core tablet is dissolved, resulting in the release of the reducing agent and catalyst. No chemical reaction involving the thin lacquer polymeric coating is taught or suggested to increase the overall rate of dissolving this coating.

Schafer et al European Patent Application 86109,361.5 discloses a hydrogen peroxide neutralizer tablet covered with a coating to delay the dissolution of the tablet. The coating can be made of a dimethylaminomethacrylate/neutral methacrylic acid esters polymer soluble in an acid environment. Such polymers, for example the cationic resin sold by Rohm Pharma under the Trademark Eudragit E, are soluble in acidic aqueous media having pHs of 5 or less. Since hydrogen peroxide-containing liquid aqueous media used to disinfect contact lenses often have pHs of 4 to 5, such cationic resins may not be satisfactory as delayed release coatings in the lens disinfecting context since the resin may dissolve and release the hydrogen peroxide destroying component before the lens is effectively disinfected. The coating can alternately be made of a methacrylic acid/methacrylic acid methyl ester polymer soluble in an pH neutral solution. Such pH neutral soluble polymers, for example the polymer sold by Rohm Pharma under the Trademark Eudragit S, are substantially insoluble in acidic aqueous media and are soluble in aqueous media having pHs of 7 or more.

There continues to be a need for a one step contact lens disinfecting system using a hydrogen peroxide destroying component. The delayed release coating should be such as to allow enough time for lens disinfecting to take place while, at the same time allowing release of the hydrogen peroxide destroying component in a reasonable period of time so that the residual hydrogen peroxide can be rapidly destroyed and the disinfected lens can be safely and comfortably worn.

SUMMARY OF THE INVENTION New compositions and methods useful for destroying hydrogen peroxide in a liquid aqueous medium, in particular for destroying residual hydrogen peroxide in a liquid aqueous medium containing a disinfected contact lens, have been discovered. The present invention allows the hydrogen peroxide destroying component or components to be initially contacted with the liquid aqueous medium at the same time the contact lens to be disinfected is initially contacted with liquid aqueous medium. For example, the present compositions and the contact lens to be disinfected can be added to the liquid aqueous medium at substantially the same time. This feature greatly reduces the amount of user time and care required to effectively disinfect his/her lenses and destroy the residual hydrogen peroxide. Better user compliance and a greater degree of user eye safety is provided. The present invention provides a delayed release feature so that the contact lens is effectively disinfected by the action of hydrogen peroxide prior to the release of the hydrogen peroxide destroying component. Also, the present composition is structured so as to provide for rapid release of the hydrogen peroxide destroying agent into the medium. This rapid release feature provides for rapid destruction of the residual hydrogen peroxide after a delayed release of the peroxide destroying component. Thus, the overall time required to both disinfect the lens and destroy the residual s peroxide is reduced, thus making contact lens disinfecting more convenient and easy to practice. Further, the composition has increased solubility in the medium so that preferably little or no solid material from the composition remains in the medium after the hydrogen peroxide has been destroyed .

In one broad aspect, the present invention is directed to a composition including a coated portion or core, e.g., coated core tablet, containing at least one hydrogen peroxide destroying component, and a barrier coating. The hydrogen peroxide destroying component, hereinafter referred to as HPDC, is effective when released into a liquid aqueous medium to destroy or cause the destruction of hydrogen peroxide present in the liquid aqueous medium. The barrier coating acts to substantially prevent the release of the HPDC for a period of time after the composition is initially contacted with a hydrogen peroxide-containing liquid aqueous medium, hereinafter referred to as HPLM. The barrier coating includes material capable of at least partially dissolving in an aqueous medium, i.e., an acidic liquid aqueous medium, having a pH in the range of 5.1 to 6.9 by forming one or more soluble salts of the material. This chemical dissolution. i.e., dissolution as the result of forming one or more soluble salts of the material, accelerates the overall dissolution, i.e., the sum of the physical dissolution and chemical dissolution, of the material, and ultimately of the barrier coating, so that the HPDC is released more rapidly and preferably the amount of solid material from the barrier coating remaining in the liquid aqueous medium after hydrogen peroxide destruction is substantially reduced.

The barrier coating preferably includes a major amount, i.e., at least about 50% by weight, more preferably at least about 80% by weight, of one or more of such materials. These materials are preferably polymeric, more preferably polymers derived from a monomer selected from the group consisting of methacrylic acid, methacrylic acid esters and mixtures thereof. The polymeric materials are preferably anionic in character.

A method for decreasing the concentration of hydrogen peroxide in a HPLM is provided in which a HPLM is contacted with a composition, e.g., as described herein.

Further, a method of disinfecting a lens, preferably a contact lens, is provided. This method includes contacting a lens to be disinfected with a HPLM at effective lens disinfecting conditions to disinfect the lens. The HPLM is also contacted with a composition, e.g., as described herein.

This composition preferably produces a liquid aqueous medium having no deleterious concentration of hydrogen peroxide. Thus, after the composition has acted, the disinfected contact lens can be removed from the liquid aqueous medium and placed directly in the eye.

DETAILED DESCRIPTION OF THE INVENTION The present invention is of value where hydrogen peroxide is used to disinfect lenses, e.g., contact lenses, which are benefited by periodical disinfecting. Such lenses, e.g., conventional 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 present invention is particularly useful for destroying residual hydrogen peroxide in a HPLM which has been used to disinfect a contact lens.

The liquid medium used to disinfect a contact lens 10 in the present invention includes a disinfecting amount of hydrogen peroxide. Preferably, a disinfecting amount of hydrogen peroxide means such amount as will reduce the microbial burden by one log 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 unit 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. Relatively mild aqueous hydrogen peroxide solutions, preferably containing about 0.5% to about 6% of hydrogen peroxide (w/v), 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 HPLM, the residual hydrogen peroxide, e.g., on the lens, should be destroyed so that the lens may be safely and comfortably worn on the eye. If this residual hydrogen peroxide is not destroyed before the lens is worn, irritation to the eye or wearing discomfort may occur.

Thus, the present compositions, which are preferably initially contacted with the HPLM at substantially the same time as the contact lens to be disinfected, allow for IE 91646 effective lens disinfection and, in addition, effectively destroy the residual hydrogen peroxide remaining in the HPLM so that the disinfected lens can be removed from the liquid medium and placed directly into the eye for safe and comfortable wear. The present composition is preferably present in the form of a tablet. The composition may be present in the form of at least one item, e.g., tablet, which includes 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 composition, while the barrier coating is preferably about 1% to about 60% by weight of the total composition.

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; Nacetylcysteine; 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. One important advantage of the present invention is the rapidity with which the HPDC acts to destroy residual hydrogen peroxide once the HPDC is initially released into the HPLM. The present barrier coating can be very precisely formulated so that the amount of time after the composition is introduced into the HPLM but before the HPDC is released into the HPLM is very effectively controlled. After this period of time, the barrier coating is at least partially chemically dissolved, as described herein, into the HPLM sufficiently to facilitate the rapid release of sufficient HPDC to destroy the remaining or residual hydrogen peroxide. The present compositions are preferably formulated and structured to provide for delayed release of the HPDC into the HPLM for a time sufficient to allow the hydrogen peroxide to effectively disinfect a contact lens, and then to release the HPDC into the HPLM 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 HPLM 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 activity/percent (w/v) of hydrogen peroxide in the HPLM/ml of HPLM. 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 peroxideactive 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 HPLM to the detriment of the activity of the enzyme. Metalloproteases, 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 Streptomyces bacteria and Asperiglllus 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 form Bacillus Species Biochemical and Biophysical Research Comm., Vol 34, No. 5, pp 600-604, (1969).

The subtilisin enzymes are broken down onto two subclasses, subtilisin A and subtilisin B. In the subtilisin A grouping are enzymes derived from such species are B. subtllis, B. licheniformis and B. 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 a B. subtilis, B. subtilis var. amylosacchariticus, B. amyloliquefaciens 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, collaginase, keratinase, carboxylase, aminopeptidase, elastase, and aspergillopeptidase A and B, pronase E (from S. griseus) and dispase (from Bacillus polymyxa).

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 barrier coating of the present invention is preferably substantially continuous. By continuous is meant that the barrier coating completely isolates the coated portion for a time after the present composition is first contacted with, e.g., submerged in, a HPLM. The barrier coating is at least partially water soluble, preferably substantially completely water soluble.

The barrier coating includes at least one material capable of at least partially dissolving in an aqueous medium, e.g., an aqueous medium containing at least one buffering agent or buffer, having a pH in the range of 5.1 to 6.9, preferably about 5.3 to 6.5, by forming one or more soluble salts of the material or materials. Thus, the present barrier coating is at least partially chemically dissolvable in such aqueous media. Without wishing to limit the invention to any particular theory of operation, it is believed that the barrier coating begins to dissolve from the time the present composition, including a coated portion or core and a barrier coating, is initially contacted with the HPLM, which preferably has a pH of about 4 to 5. This early dissolving is a physical (non-chemical) phenomenon. As this physical dissolving continues, the HPLM acts to effectively disinfect the contact lens in the HPLM. In addition, this physical dissolving causes small amounts of HPDC, and preferably buffer, to be released from the coated core. This, in turn, causes the pH of the HPLM to increase beyond 5. At this point, at least a portion of the barrier coating becomes susceptible to chemical dissolution by soluble salt formation so that the overall rate of barrier coating dissolution increases substantially. This combined physical/chemical dissolution of the barrier coating rapidly releases the HPDC to rapidly destroy the residual hydrogen peroxide. Also, this combined physical/chemical dissolution increases the overall amount of the barrier coating which is solubilized in the liquid medium. Ultimately, the pH of the liquid medium reaches a value of about 7.0 to 7.5, e.g., about 7.3. At this point, substantially all of the hydrogen peroxide has been eliminated from the liquid aqueous medium, and the disinfected contact lens can be removed and placed directly into the wearer's eye for safe and comfortable wear.

Any material or combination of materials which is ophthalmically acceptable and has the capability of forming soluble salts in an aqueous medium, in particular a liquid aqueous medium containing hydrogen peroxide, having a pH of .1 to 6.9 may be employed in the barrier coating of the present invention. Such material or materials preferably comprise a major amount, i.e., at least about 50% by weight, more preferably at least about 80% by weight, of the barrier coating. Such material or materials are preferably polymeric.

Particularly useful are anionic polymeric materials. One very useful class of materials are polymers derived from a monomer selected from the group consisting of methacrylic acid, methacrylic acid esters and mixtures thereof. Particularly useful are copolymers of methacrylic acid and at least one methacrylic acid ester in which the ratio of free carboxyl groups to ester groups is about 0.7 or greater, especially about 1 or greater. Among the methacrylic acid esters which can be employed as monomers, methacrylic acid methyl ester is preferred.

The barrier coating preferably includes at least one plasticizer component in an amount effective to increase the elasticity of the coating. Thus, without the plasticizer component, the barrier coating may be or become relatively brittle so that an even relatively minor impact may destroy the coating's integrity. The plasticizer component acts to reduce this impact risk. Any suitable plasticizer component may be employed. Examples of plasticizer components which may be included in the present barrier coatings are polyethylene glycols, dibutyl phthalate, glycerol triacetate, caster oil, 1, 2-propylene glycol, citric acid esters, such as triethyl citrate, and mixtures thereof. In one embodiment, the barrier coating is preferably substantially free of polyhydric alcohols. The plasticizer component preferably is present as a minor portion, i.e., less than about 50% by weight, and more preferably less than about 20% by weight, of the barrier coating.

The barrier coating may be applied to the core in any suitable manner, provided that the final composition performs as described herein. Various conventional and well known coating procedures may be employed. One useful approach involves dissolving the component or components of the barrier coating in a liquid solvent and then applying the solvent containing the dissolved barrier coating to the core. The solvent is then evaporated, leaving the barrier coating on the core. Volatile organic solvents, such as acetone and the like, may be employed to dissolve the barrier coating component or components. The solvent containing the dissolved component or components may be sprayed onto the core or the core may be dipped into the solvent/barrier coating component mixture. A single core may be subjected to more than one application of this mixture in order to get the desired thickness of barrier coating.

An additional embodiment of the present invention provides for a composition in which at least one enzyme capable of removing debris from a contact lens, as described elsewhere herein, is included separate and apart from the HPDC. Preferably, in this embodiment, the composition is present in the form of at least one item, e.g., a tablet, comprising a coated core, a barrier coating and a second coating. The second coating includes the enzyme, and the coated core includes the HPDC. The second coating preferably substantially surrounds the barrier coating, which, preferably, substantially surrounds the coated core. Using this embodiment, the contact lens is preferably cleaned of debris at the same time the contact lens is disinfected.

As noted above, one or more enzymes useful to remove debris from a contact lens can be included with the HPDC or can be located in a second coating. Conventional techniques can be employed to place a second coating containing such enzyme or enzymes on the coated core, produced as discussed previously.

The present method of disinfecting a lens, preferably a contact lens, includes contacting the lens to be disinfected with a HPLM at effective lens disinfecting conditions. The HPLM is contacted with a composition which includes a coated portion containing at least one HPDC and a barrier coating, such as described herein. Using this method, the lens is disinfected and the residual hydrogen peroxide in the HPLM is effectively destroyed. Thus, after the HPDC has been released into the HPLM 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 a particularly useful embodiment, the contact lens to be disinfected is placed into the HPLM at substantially the same time as is the present composition. After a predetermined period of time, during which the contact lens is disinfected, the HPDC is released into the HPLM and effectively destroys the residual hydrogen peroxide.

In the event that a debris removing enzyme is present in the composition, 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, e.g., if the enzyme is released into the HPLM when the composition is initially contacted with the HPLM or shortly thereafter; or after the lens is disinfected, e.g., if the enzyme is released into the HPLM when the HPDC is released into the HPLM or thereafter.

It is preferred that the HPDC not be released into the HPLM until the lens has been immersed in the HPLM for a time sufficient, more preferably in the range of about 1 minute to about 4 hours and still more preferably in the range of about 5 minutes to about 1 hour, to effectively disinfect the lens. It is also preferred that substantially all of the residual hydrogen peroxide in the HPLM 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 HPLM.

The disinfecting contacting preferably occurs at a temperature to maintain the liquid medium substantially liquid. For example, when the liquid medium is aqueous-based, 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. Such contacting times can be in the range of about 1 minute to about 12 hours or more.

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

EXAMPLE 1 A two layer tablet, having a core tablet surrounded by a coating was prepared for testing. The core t 25 coating had the following compositions: CORE TABLET Crystalline catalase (1 1.5 mg Sodium chloride 89.4 mg 30 Dibasic sodium phosphate (anhydrous) 12.0 mg Monobasic sodium 35 phosphate monohydrate 1.0 mg Polyethylene glycol (molecular weight of about 3350) 1.0 mg IE 91646 COATING Copolymer of Methacrylic^2^ 4.15 mg Acid and Methacrylic Acid Methyl Ester — Glycerol triacetate^) 0.35 mg (1) The amount of catalase added was determined by an assay of the batch of product to be used. The tablet prepared contained about 5200 units of catalase activity. (2) Sold by Rohm Pharma under the trademark Eudragit L. Copolymer has a mean molecular weight of 135,000 and a 1:1 ratio of free carboxyl groups to ester groups. This copolymer dissolves in a buffered liquid aqueous medium having a pH of about 6.0 by forming soluble salts. (3) A plasticizer The coating was applied to the core tablet by dipping the core tablet into a solution of the coating materials in acetone.

This layered tablet was tested to determine its effectiveness in destroying hydrogen peroxide. This test was conducted as follows. 10 ml of a 3% (w/v) aqueous solution of hydrogen peroxide was provided at room temperature. The layered tablet was introduced into the solution and periodic measurements of the amount of oxygen released from the solution were made. The amount of oxygen released was used to determine the hydrogen peroxide concentration remaining in the solution.

Results of this test were as follows: IE Time After Tablet Introduced Into Solution, min.

Peroxide Concentration In Solution % w/v 3.07 3.04 2.97 2.93 6 2.89 2.84 2.78 2.72 2.64 11 2.37 2.13 1.84 1.07 0.42 22 0.11 0.05 0.03 0.01 0 32 0 EXAMPLE 2 (COMPARATIVE) Example 1 was repeated except that the copolymer used in Example 1 is replaced by a copolymer of methacrylic acid and methacrylic acid methyl ester sold by Rohm Pharma under the Trademark Eudragit S. The copolymer used in Example 2 has a mean molecular weight of 135,000, a 1:2 (0.5) ratio of free carboxyl groups to ester groups and dissolves in a buffered liquid aqueous medium having a pH of about 7.0 by forming soluble salts.

Results of the test to determine the effectiveness in destroying hydrogen peroxide of the coated tablet of Example 2 was as follows: ¢0 Time After Tablet Introduced Into Solution, min.

Peroxide Concentration In Solution % w/v 1 3.10 5 3.09 10 3.07 20 3.02 25 2.98 10 30 2.88 32 2.79 35 2.58 40 2.11 45 1.71 15 50 1.39 58 0.97 60 0.87 66 0.61 70 0.46 20 75 0.27 80 0.13 86 0.04 92 0.03 95 0.01 25 100 0 105 0 The results from Examples 1 and 2 indicate that both coatings function quite well to provide the desired delayed release feature, e.g., so that a contact lens can be effectively disinfected by the hydrogen peroxide present in the aqueous solution, and to ultimately release sufficient catalase to destroy substantially all of the hydrogen peroxide. However, there were substantial performance advantages for the coated tablet of Example l relative to the coated tablet of Example 2. A substantially greater portion of the coating in Example 2 remained undissolved. This undissolved coating may hinder the release of the catalase and the destruction of the hydrogen peroxide. Further, in the contact lens disinfecting context, the presence of a relatively large portion of the coating material may confuse the lens wearer as to whether or not the disinfection process IE 91646 is complete. It is quite advantageous to more completely dissolve the coating during the contact lens disinfecting process.

An additional advantage of the Example 1 tablet relative to the Example 2 tablet is the speed with which the residual hydrogen peroxide concentration was eliminated. For example, in Example 1 it took only 16 minutes to destroy 2.1% hydrogen peroxide, while in Example 2 the same amount of hydrogen peroxide destruction took fully 56-60 minutes. Once contact lens disinfection has taken place, it is advantageous to rapidly destroy the residual hydrogen peroxide. For example, the faster the hydrogen peroxide is destroyed, the faster the contact lens can be safely and comfortably worn.

EXAMPLE 3 A layered tablet is prepared as in Example 1 except that sufficient subtilisin A is included in the core tablet to provide the core tablet with about 0.4 mg of this enzyme.

This enzyme containing tablet is used to disinfect and clean a protein-based debris laden soft contact lens as follows. 10 ml of a 3% (w/v) aqueous solution of hydrogen peroxide is provided at room temperature. The contact lens to be disinfected and cleaned and the enzyme-containing layered tablet are placed in the solution at the same time.

For approximately one-half hour the solution remains substantially quiet. For the next approximately 5 to 10 minutes, the solution bubbles. After this period of time, the solution becomes and remains quiet. 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.

EXAMPLE 4 A layered tablet is prepared as in Example 1, 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 core tablet with about 0.4 mg of this enzyme.

This enzyme-containing tablet is used to disinfect and clean a protein-based debris laden soft contact lens substantially as described 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 this disinfected and cleaned contact lens .

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.

Claims (38)

1. A composition comprising a coated core containing at least one hydrogen peroxide destroying component effective when released into a liquid aqueous medium to destroy or cause the destruction of hydrogen peroxide present 5 in the liquid aqueous medium, and a barrier coating acting to substantially prevent the release of said hydrogen peroxide destroying component for a period of time after said composition is initially contacted with a hydrogen peroxidecontaining liquid aqueous medium, said barrier coating 10 including material capable of at least partially dissolving in an aqueous medium having a pH in the range of 5.1 to 6.9 by forming one or more soluble salts of said material.

2. The composition of claim 1 wherein said material is at least a major portion of said barrier coating.

3. The composition of claim 1 wherein the aqueous medium contains hydrogen peroxide and has a pH in the range of about 5.3 to about 6.5.

4. . The composition of claim 1 wherein said material is polymeric.

5. The composition of claim 4 wherein said polymeric material is derived from a monomer selected from the group consisting of methacrylic acid, methacrylic acid esters and mixtures thereof.

6. The composition of claim 4 wherein said polymeric material is derived from methacrylic acid, and at least one methacrylic acid ester in which the ratio of free carboxyl groups to ester groups is about 0.7 or greater. IE 91646

7. The composition of claim 6 wherein said polymer is anionic in character and is derived from methacrylic acid and methacrylic acid methyl ester.

8. The composition of claim 1 wherein said barrier coating is substantially free of polyhydric alcohols.

9. The composition of claim 1 wherein said coated core further includes at least one buffer component.

10. The composition of claim 1 wherein said composition is in the form of a tablet.

11. The composition of claim 1 wherein said barrier coating further includes at least one plasticizer component in an amount effective to increase the elasticity of said barrier coating.

12. The composition of claim 1 where said hydrogen peroxide destroying component is selected from the group consisting of hydrogen peroxide reducing agents, peroxidases and mixtures thereof.

13. The composition of claim 1 where said hydrogen peroxide destroying component is catalase.

14. The composition of claim 1 which further comprises at least one enzyme capable of removing debris from a contact lens in an amount effective to substantially remove at least one type of debris from a debris laden contact lens, 5 said composition being structured so that when said composition is contacted with a hydrogen peroxide-containing liquid aqueous medium said enzyme is released into the hydrogen peroxide-containing liquid aqueous medium before or IE 91646 at substantially the same time as said hydrogen peroxide 10 destroying component is released.

15. The composition of claim 14 which further comprises a coating layer containing said enzyme.

16. The composition of claim 14 wherein said enzyme is selected from the group consisting of peroxide active enzymes and mixtures thereof.

17. A method of decreasing the concentration of hydrogen peroxide in a liquid aqueous medium comprising: contacting a hydrogen peroxide-containing liquid aqueous medium with a composition comprising a coated core $ containing at least one hydrogen peroxide destroying component effective when released into said hydrogen peroxide-containing liquid aqueous medium to destroy or cause the destruction of hydrogen peroxide present in said hydrogen peroxide-containing liquid aqueous medium, and a barrier coating acting to 10 substantially prevent the release of said hydrogen peroxide destroying component for a period of time after said composition is . initially contacted with said hydrogen peroxide-containing liquid aqueous medium, said barrier coating including material capable of at least partially 15 dissolving an aqueous medium having a pH in the range of 5.1 to 6.9 by forming one or more soluble salts of said material.

18. The method of claim 17 wherein said hydrogen peroxide destroying component is released into said hydrogen peroxide-containing liquid aqueous medium at a predetermined time after said composition is initially contacted with said 5 hydrogen peroxide-containing liquid aqueous medium and said material is at least a major portion of said barrier coating.

19. The method of claim 17 wherein the aqueous medium contains hydrogen peroxide and has a pH in the range of about 5.3 to about 6.5.

20. The method of claim 17 wherein said material is derived from a monomer selected from the group consisting of methacrylic acid, methacrylic acid esters and mixtures thereof.

21. The method of claim 17 wherein said polymeric material is derived from methacrylic acid, and at least one methacrylic acid ester in which the ratio of free carboxyl groups to ester groups is about 0.7 or greater.

22. The method of claim 21 wherein said copolymer is anionic in character and is derived from methacrylic acid and methacrylic acid methyl ester.

23. A method of disinfecting a lens comprising: contacting a lens to be disinfected with a hydrogen peroxide-containing liquid aqueous medium at effective lens disinfecting conditions, thereby disinfecting said lens; and 5 contacting said hydrogen peroxide-containing aqueous liquid medium with a composition comprising a coated core containing at least one hydrogen peroxide destroying component effective when released into said hydrogen peroxide-containing liquid aqueous medium to destroy or cause the destruction of 10 hydrogen peroxide present in said hydrogen peroxide-containing liquid aqueous medium, and a barrier coating acting to substantially prevent the release of said hydrogen peroxide destroying component for a period of time after said composition is initially contacted with said hydrogen 15 peroxide-containing liquid aqueous medium, said barrier coating including material capable of at least partially dissolving in an aqueous medium having a pH in the range of 5.1 to 6.9 by forming one or more soluble salts of said material.

24. The method of claim 23 wherein said composition is structured so that said hydrogen peroxide destroying component is released into said hydrogen peroxide-containing liquid aqueous medium at a predetermined time after said composition is initially contacted with said hydrogen peroxide-containing liquid aqueous medium.

25. The method of claim 23 wherein said material is at least a major portion of said barrier coating.

26. The method of claim 23 wherein the aqueous medium contains hydrogen peroxide and has a pH in the range of about 5.3 to about 6.5.

27. The method of claim 23 wherein said material is polymeric.

28. The method of claim 27 wherein said polymeric material is derived from a monomer selected from the group consisting of methacrylic acid, methacrylic acid esters and mixtures thereof.

29. The method of claim 27 wherein said polymeric material is derived from methacrylic acid, and at least one methacrylic acid ester in which the ratio of free carboxyl groups to ester groups is about 0.7 or greater.

30. The method of claim 29 said polymer is anionic in character and is derived from methacrylic acid and methacrylic acid methyl ester.

31. The method of claim 23 wherein said barrier coating is substantially free of polyhydric alcohols.

32. The method of claim 23 wherein said coated core further includes at least one buffer component.

33. The method of claim 23 where said hydrogen peroxide destroying component is selected from the group consisting of hydrogen peroxide reducing agents, peroxidases and mixtures thereof.

34. The method of claim 23 where said hydrogen peroxide destroying component is catalase.

35. The method of claim 23 which further comprises releasing into said hydrogen peroxide-containing aqueous medium at least one enzyme capable of removing debris from a 5 contact lens in an amount effective to substantially remove at least one type of debris from a debris laden contact lens, said enzyme being released into said hydrogen peroxidecontaining liquid aqueous medium before or at substantially the same time as said hydrogen peroxide destroying component is released.

36. The method of claim 35 wherein said enzyme is selected from the group consisting of peroxide active enzymes and mixtures thereof.

37. A hydrogen peroxide destroying composition substantially as hereinbefore described by way of Example.

38. A method of disinfecting a lens substantially as hereinbefore described by way of Example.