Background of the Invention

The present invention relates to compositions and methods for treating contact lenses, and to lenses which have acquired certain properties. More particularly, the invention relates to compositions and methods for removing irritant biological molecules (hereinafter IBMs) from contact lenses, which molecules can have adverse effects on the lens wearer's eyes, as well as to lenses which have acquired a freedom from contamination with IBMs.

Contact lenses need to be periodically treated, for example, cleaned, because of the tendency for a variety of materials to accumulate on the lenses . Among the materials that may accumulate on contact lenses are proteins, glycoproteins, lipids, as well as foreign matter, such as eye makeup. Unfortunately, many lens treating systems cause excessive lens wear and/or damage, such as when the system employs an abrasive component. Excessive wear due to the lens treating system is especially common with "soft" contact lenses because of the relatively low resistance to abrasion of such lenses. Accordingly, lens treatment systems that effectively perform their desired function, such as cleaning or disinfecting the lens, without causing undue lens wear are advantageous.

Other lens treating systems are designed to react biochemically with the protein and lipoprotein deposits. Hence, such biochemical reactants, for example enzyme compositions, are not intended to be effective in removing all biological contaminants, but only those with which the enzyme is capable of reacting.

Many lens treating systems can cause damage and irritation to the ocular surface. For example, strong oxidants, such as hydrogen peroxide, solvents, such as chloroform, detergents, such as sodium lauryl sulfate, or proteolytic enzymes can damage or irritate the eye, when concentrations necessary to clean lenses are placed in direct contact with the ocular surface. Accidental exposure of the eye to lens cleaning solutions may occur. Alternatively, a very safe and convenient solution would be one which could clean the lens while it was in the eye. Accordingly, lens treatment systems which effectively perform their desired function, such as cleaning or disinfecting the lens, without causing ocular damage or irritation are advantageous.

A number of cleaning systems have been proposed for contact lenses. For example, Su et al U.S. Patent No. 5,037,484 proposes the use of a cleaning composition that contains a particulate organic polymer or polysiloxane particles suspended in a carrier. The carrier usually includes a thickening agent in order to keep the polymeric particles in suspension. The thickening agent itself is not reported to have any cleaning effect on the contact lens. Due to the relative inelasticity or rigidity of these particles, it is not likely that they can provide sufficient softness to avoid lens abrasion or scratching.

Another approach to treating contact lenses, in particular to disinfect contact lenses, is described by Schafer et al U.S. Patent No. 5,011,661. Microbes on the contact lens are destroyed by immersing the lens in a disinfecting solution. The disinfectant, such as hydrogen peroxide, is decomposed by contacting it with a catalytic neutralizing agent, which is typically enveloped by a polymeric coating that acts to retard the decomposition of disinfectant in a controlled fashion. This system is not reported to be effective

in removing non-microbial debris, such as proteinaceous deposits, from the lens, so that a separate system of removal of these materials is required. Further, the polymeric coating on the neutralizing agent is not indicated to be effective in removing deposit materials from the contact lens.

Another approach proposed for cleaning contact lenses is described by Bhatia U.S. Patent Nos. 4,921,630 and 4,839,082 wherein a chemical formulation purportedly forms an abrasive precipitate when rubbed on the surface of the lens. The abrasive precipitate is believed to scour deposits from the lens as a user manually rubs the precipitate against the lens surface. One formulation includes a carboxy vinyl polymer in solubilized form, which polymer apparently precipitates from solution upon contacting the lens, hypothetically because of "water loss" from the polymer-containing composition and takeup of the water by the lens. Hence, the abrasive precipitate formed is believed to be composed primarily of precipitated polymer. The polymer is not believed to be effective in removing deposit materials from the contact lens other than by abrasion.

Yet another system for cleaning contact lenses is proposed by Chromecek et al U.S. Patent No. 4,655,957, which describes a particulate hydrophilic polymer or copolymer, typically in bead form, that is purportedly effective in removing lens deposits. Since the composition is only reported to be effective in removing lens deposits when provided in particulate form, it is possible the composition achieves deposit removal by abrading the material from the lens surface. edler U.S. Patent No. 5,328,846, describes compositions and methods for removing mucin or mucin- containing deposits from hydrophilic contact lenses.

Lloyd et al U.S. Patent No. 4,421,665, discloses the use of non-polar solvents, such as cyclohexane,

ethyl acetate, chloroform, petroleum ether, hexane, and benzene, to dissolve lipids and lipoproteins which are deposited on contact lenses during usage.

Winterton et al U.S. 4,734,222, describes a contact lens cleaning composition and method wherein the lens cleaning material is water-soluble and dispersed in a non-aqueous liquid medium.

It has been discovered that one source of eye irritation to contact lens wearers is the presence of certain biological molecules or materials on the lens. Further it has been found that these biological molecules or materials are not satisfactorily removed by prior art compositions and methods.

It would be advantageous to provide a contact lens treatment system that effectively removes deposited irritant biological molecules or materials, hereinafter referred to as "IBMs", from the contact lens, is not irritating to the eye, and avoids detrimental abrasion or scratching of the lens.

Summary of the Invention

New compositions and methods for treating contact lenses to remove IBMs, as well as novel contact lenses, have been discovered. The compositions and methods are particularly useful in removing IBMs which are not effectively removed by prior art techniques and compositions. In other words, such IBMs remain with the lenses even after prior art treatments to the extent that lenses with such amounts of IBMs when worn in a human eye cause eye discomfort and/ or irritation and/or other detrimental effects on the eye as a result of the presence of such IBMs. The present invention preferably reduces the level of IBMs on contact lenses so that the IBMs remaining on the lenses are present in a non-irritating quantity.

IBMs removable herein encompass a number of protein, lipoprotein, and lipid materials which are formed or generated, for example, naturally generated, in the eye during contact lens wear. One class of

lipids associated with an irritant effect upon contact lens wearers is known as eicosanoids. Eicosanoids are 20 carbon chain unsaturated lipids derived from arachidonic acid or other fatty acids. Eicosanoids include pro s t ag1 andi s , 1 e ko t r i e ne s , hydroxyeicosatetraenoic acids and thromboxanes. Platelet activating factor, l-O-alkyl-2-acetyl-sn- glycero-3-phosphocholine, is a related lipid with irritant properties. Other IBMs include cytokines, such as IL-1 _/ 8, IL-6, IL-8, IFN-γ, and TGF-/S, adhesion molecules such as ICAM-1, VCAM-1, and E-selectin, and the like; inflammatory mediators, such as bradykinin, eosinophil chemotactic factor, serotonin, histamine and the like; and various materials produced by the action of microbes, such as endotoxins, exotoxins and the like.

In one embodiment, the present compositions comprise a solid component including a matrix material and an irritant biological molecule or material removal component, hereinafter referred to as "IBMRC" immobilized in the matrix material and present in an amount effective to reduce the amount of IBMs contaminating a contact lens contacted with the composition. A preferred composition is one useful for removing eicosanoids.

In a useful embodiment, the present compositions comprise a liquid medium including water, an IBMRC combined with the liquid medium in an amount effective to interact with IBMs on a contact lens contaminated with the IBMs and immersed in the liquid medium to reduce the amount of IBMs contaminating the contact lens. The IBMRC may be soluble or insoluble, preferably soluble, in the liquid medium.

The present compositions may comprise a lipid solubilization component present in a liquid medium, preferably an aqueous-based liquid medium, in an amount effective to increase the solubility of IBMs, for example eicosanoids, in the liquid medium. More preferably the lipid solubilization component is

selected from carboxylic acids having from about 8 to about 30 carbon atoms, triglycerides having from about 12 to about 40 carbon atoms, naturally occurring oils, polyalkylglycosides, and mixtures thereof. The above compositions are particularly preferred for use when the IBM is an eicosanoid. When eicosanoids are one of the target IBMs to be removed, the IBMRC is preferably selected to remove eicosanoids. In one embodiment, methods of the present invention comprise contacting a contact lens contaminated with IBMs with a liquid medium which includes water, and a solid component including a matrix material and an IBMRC immobilized in or on the matrix material . The IBMRC is present in an amount effective to reduce the amount of IBMs contaminating the contact lens.

Very useful methods of this invention comprise contacting a contact lens contaminated with IBMs with a liquid medium including water and an IBMRC in an amount effective to interact with the IBMs and reduce the amount of IBMs available to contaminate the contact lens.

Additional methods for removing IBMs from a contact lens comprise contacting the contact lens contaminated with the IBMs with a liquid medium including water and a lipid solubilization component in an amount and at conditions effective to increase the solubility of said IBMs in the liquid medium.

Contact lenses, previously exposed to the IBMs because of their presence in the eye, and which have been treated in accordance with this invention, have an IBM content sufficiently low so that such IBMs cause no substantial or significant eye irritation or other detrimental effect to the eyes in which the treated lenses are worn. Such treated lenses preferably have at least about 50% and preferably at least about 75% by weight of IBMs removed from lens by comparison to the

IBM concentration prior to treatment. More preferably, the IBM content of such treated lenses is in the range of about 50% by weight or less of the amount of IBMs which were present on the lens prior to treatment of the lens to remove IBMs. More preferably, the IBM concentration on the lens is reduced to at least 25 % or less, and even more preferably to at least 10% or less, by weight of the IBMs which were present on the lens prior to treatment of the lens to remove IBMs. These and other aspects and advantages of the present invention will be apparent from the following detailed description and claims.

Detailed Description of the Invention Any contact lens, for example, conventional hard contact lenses, rigid gas-permeable contact lenses, and soft contact lenses, can be treated in accordance with the present invention. In one broad aspect, the present invention is directed to compositions useful for treating, for example, cleaning, a contact lens.

In one embodiment, the present compositions comprise a solid component which includes a matrix material and an IBMRC. The IBMRC is preferably immobilized in or on the matrix material, at least before the composition is placed in contact with the contact lens.

Suitable matrix materials include a large number of base polymeric materials and other materials which can act as a support, diluent, and/or dispersant for the IBMRC, and which are compatible with the contact lenses to be treated. The matrix material can provide one or more other functions in the present compositions as well, such as a polish or mild abrasive for the lens material. Synthetic (man-made) and naturally occurring polymeric and non-polymeric substances can be used as matrix materials. Examples of useful matrix materials

include crosslinked polysaccharides; polyacrylamides; hydrophilic acrylic and methacrylic polymers and copolymers; copolymers of saccharides and acrylamides; a number of water-insoluble polymers including polyolefins such as polyethylene and polypropylene; polyamides such as nylon; polyvinyl-pyrrolidone; polyvinylacetate; polyvinyl alcohol; silicone polymers; inorganic oxides such as glass; and the like and mixtures thereof. Proteins are one preferred class of naturally occurring matrix materials useful herein. A number of cellulosic materials such as rayon, modified textile fibers, and the like are also useful matrix materials. Matrix materials are preferably polymeric materials which can be converted into a granular or powdered form. Also preferred are those matrix materials which are not so hard and abrasive that they are likely to scratch the contact lens being cleaned. It is desirable that the matrix material be capable of binding the IBMRC in a manner which holds the removal component to the matrix while simultaneously permitting the removal component act upon the IBMs which are or have contaminated the contact lens being treated. That is, the matrix should not encapsulate the removal component nor bind it so tightly that the removal component cannot act upon the IBMs.

The IBMRCs are useful in removing IBMs, for example, IBMs which have not been effectively removed from previously worn contact lenses by prior art compositions and techniques. The IBMRCs used in this invention are preferably effective in removing IBMs not effectively removed by prior art compositions with no undue or discernable adverse effects upon the contact lens or the contact lens wearers using the treating compositions.

It is also important that the IBMRC and the compositions in which they are included are compatible

with the lenses being treated to remove IBMs. The compositions and the IBMRC should not be so abrasive that the lens surface is detrimentally scratched or the lens is otherwise detrimentally affected, nor be so difficult to remove from the lens that wearers are adversely affected by the residual materials on the lenses.

Particularly useful IBMRCs include those which are capable of attracting or binding with hydrophobic moieties on the IBMs, and/or those which are capable of attracting or binding with ionic, especially anionic, groups on the IBMs. Even more preferred are IBMRCs covalently bonded to the matrix materials. Such covalently bonded IBMRCs remain bound to the matrix as the matrix is removed from the lens, thereby facilitating a more complete removal of the IBMs from the contact lens. In addition, such covalent bonding to an insoluble matrix material maintains the IBMRC separate from the lens. Also, IBMs which become bound, for example, chemically bound or complexed to an IBMRC immobilized on a solid matrix material, are not available to redeposit on, or otherwise contaminate the lens being treated.

Examples of useful IBMRCs which can be immobilized on a matrix material include ionically charged, preferably anionically charged, components, such as those containing one or more alkyl groups and/or alkoxy groups having at least about four carbon atoms, aryl groups, alkaryl groups, aralkyl groups, nitro groups, amino groups, aminoalkyl groups, hydrocarbyl quaternary ammonium groups having at least about twelve carbon atoms, carboxyl groups, sulfate groups, phosphate groups, polyalkyl-glucoside components, carboxylic acid components having at least about eight carbon atoms, cyclodextrins, bile acid binding resin components, albumin components, for example, albumin and albumin derivatives, such as fatty acid-free albumin, antibody-

modified or derived components, positive charges, other suitable ionically charged components, and mixtures thereof. Because of the nature of several of the IBMs, the IBMRC can be proteinaceous. The remover can include a mixture of one or more proteins.

Formation of a complex, preferably a soluble complex, between the IBMs and the IBMRC is another alternative suitable for removing the IBMs from the lens surface. Complex formation can be one way of achieving a satisfactory bonding of IBM and IBMRC, which in turn makes it possible to remove the IBMs from the lens surface. If the complex bonds or interactions are sufficiently strong to hold the two components together as the bonds between lens and IBMRC are disrupted, then complex formation can be acceptable. That is, one problem which must be solved in removing IBMs adhered to a contact lens surface is that, once the bonds between IBMs and lens surface are disrupted, the IBMs are preferably displaced from the lens and/or corrected and/or maintained separate from the lens so that the IBMs do not reattach to or redeposit on the lens surface. If the complex bonds between IBMs and the IBMRC are sufficiently strong, they can prevent or inhibit the re-formation of bonds between IBMs and lens surface, thereby making possible a more complete removal of IBMs from the lens surface than could otherwise be obtained without complex formation.

The amount of IBMRC present in the compositions of this invention is widely variable and depends on the IBMRC itself, upon the IBMs to be removed, and upon the manner in which the IBMRC is associated with the matrix material, if any, as well as the presence or absence of liquid medium, and other factors such as the material from which the lens is made and the strength of the bonds between the IBMs and the contact lens to be treated. In general, the quantity of IBMRC used is that which effectively reduces the concentration of the

IBMs, preferably to a level at which the lens wearer experiences no discomfort or other harm from the IBMs.

The compositions containing the IBMRC can also contain a liquid medium in which the IBMRCs are dispersed, dissolved, or otherwise suspended, for example, in combination with the matrix material. One function of the liquid medium is to assist in producing effective, e.g., close contact of the IBMRC with the lens to be treated. In a preferred embodiment, the IBMRC is insoluble in the liquid medium and is dispersed therein by emulsification or simple dispersion. Examples of suitable liquid media are water, alcohols, and the like, and mixtures thereof. The liquid medium is preferably at least partly water,and more preferably at least about 25%, and even more preferably at least about 50% or more by weight of the liquid medium is water. The liquid medium is preferably aqueous-based.

Alternatively, the IBMRC can be soluble in the liquid medium. When the IBMRC is soluble in the liquid medium, rinsing the liquid from the lens surface also rinses the IBMRC from the surface. Examples of IBMRCs that are soluble or dispersable or emulsifiable (for example, without a matrix material) in liquid media include human serum albumin, bovine serum albumin, fatty acid-free albumin, ovalbumin, apolipoproteins, antibodies against the IBMs, such as against eicosanoids and cytokines, and mixtures thereof.

If the IBMRC is soluble in the liquid medium, but the bond between the IBMRC and matrix is not disrupted, an emulsified dispersion may be formed if the matrix material is sufficiently small in particle size to remain dispersed instead of settling. If the removal component is soluble in the liquid medium, the matrix need not be included in the compositions of this invention if the only purpose of the matrix is to disperse or solubilize the IBMRC. If the matrix

provides another function such as a polish or abrasive to assist in the removal of IBMs, it may be advantageous to include it in compositions of this invention even if the IBMRC is soluble in the liquid medium.

A lipid solubilization component can optionally be included in either the solid component or in the liquid medium of the compositions of this invention. The lipid solubilization component is useful in increasing the solubility of the IBMs and causing its removal from the lens surface. The amount of lipid solubilization component will vary depending upon the IBMRC, the IBMs, and the liquid medium among other factors. The amount to be used, if it is used at all, is that amount which is effective to increase the solubility of the IBMs in a liquid medium. Examples of suitable lipid solubilization components include carboxylic acids having from about eight to about thirty carbon atoms, triglycerides having from about 12 to about 40 carbon atoms, a number of naturally occurring oils such as castor oil, cottonseed oil, olive oil, and other vegetable oils, mineral oil, polyalkylglycosides, and mixtures thereof.

The solid component, comprising the matrix, IBMRC, and other ingredients, excluding the liquid medium, can be used in a particulate form, such as a granular or powdered form. One purpose of the matrix in the solid component may be to place the IBMRC in intimate contact with the lens surface to be treated. A plurality of particles, preferably small particles such as present in a powder, assists in achieving that intimate contact.

The solid component can also be formed into a sheet in which the matrix is formed into a sheet and the IBMRC is impregnated therein, deposited thereon or otherwise combined therewith. The sheet can then be used to clean a moistened or unmoistened contact lens,

after which time the sheet can be discarded and the lens rinsed to remove any residual contaminants on the lens.

The solid component can act not only to bind and release the IBMRC, but also to adsorb the IBMs and thereby reduce or prevent the redepositing of the IBMs on the lens.

One important property of the lens cleaning compositions of the invention is that they must be ophthalmically acceptable for use by users of the lenses. "Ophthalmically acceptable" means that the material must be compatible with ocular tissue, that is, it must not cause significant or undue detrimental effects when brought into contact with ocular tissue. Preferably, the ophthalmically acceptable material is also compatible with other components of the present compositions.

Although one of the principal advantages of this invention is based in part upon the discovery that there is a class of substances, i.e. IBMs, not previously treated effectively with currently available cleaning compositions, it may be advantageous to combine the compositions of this invention with one or more prior art contact lens cleaning materials to remove a combination of materials deposited on the lenses. Chemical disinfectants, enzymes, and abrasive cleansers are all possible adjuncts which can be added to the compositions of this invention to provide a combination of removal techniques. Notwithstanding the possible removal of multiple irritants and deposits through the use of a combination of cleaning ingredients, a preferred composition of this invention is one which is free of enzymes and chemical disinfectants. Particularly preferred IBMRCs include those capable of removing eicosanoids from a contact lens.

Preferred eicosanoid removal components are lipid solubilization components, more preferably those which are insoluble in an aqueous medium.

The present invention includes methods for treating contact lenses which have acquired deposits of

IBMs. Such deposits usually accumulate on the lenses during the wearing of the lenses by the wearer.

Compositions described elsewhere herein can be employed in the present methods. In one embodiment, the methods comprise contacting the lens with a liquid medium comprising water and a solid component, said solid component comprising a matrix material and an IBMRC immobilized in the matrix material in an amount effective to reduce the amount of IBMs contaminating the contact lens. Preferably, the solid component is insoluble in the liquid medium.

The treating of lenses can be accomplished by immersing the lenses in the liquid medium, or by adding drops of the liquid medium to the lenses and spreading the drops with a tissue.

The methods of this invention preferably further comprise removing the liquid medium and the IBMRC from the contact lens which has been treated. Preferably, this involves not only removing the lens from the solution or dispersion but also rinsing or wiping the lens to remove traces of the treating materials. In one embodiment, after contacting, the lens is manually rubbed at conditions effective to remove further deposited material from the lens . The methods can further comprise rinsing the contact lens substantially free of the treating composition, along with any dislodged lens deposit material .

Upon removing the lens from the liquid medium, the method described above is also effective to remove at least a portion of the IBMs, preferably more than 50%, and more preferably more than about 75%, or even more preferably more than about 90%, of the IBMs.

It is also possible to add the cleaning compositions of this invention directly to the contact

lenses while they are in the eyes of the wearer. Such an application could offer a maximum of convenience to the wearer since it would amount to the equivalent of adding eyedrops to the eye to reduce irritation and would not require the wearer to remove the lenses. With such an in si tu treatment, the IBMRC could optionally be removed by the subsequent application of a second eyedrop solution to flush the first eyedrops from the eye. In a preferred embodiment of this invention, methods for removing eicosanoids from a contact lens comprise contacting the lens contaminated with eicosanoids with a liquid medium which includes water. The medium also contains a lipid solubilization component as the eicosanoid removal component, present in an amount effective to increase the solubility of eicosanoids in the liquid medium. The lipid solubilization component can be a carboxylic acid having from about 8 to 30 carbon atoms, a triglyceride having from about 12 to about 40 carbon atoms, one or more naturally occurring oils, polyalkylglycosides, or mixtures, or derivatives thereof. One preferred embodiment is one in which the IBMRC, such as an eicosanoid removal component, is soluble in the liquid medium.

Eicosanoids are capable of being removed by the compositions of this invention in the same manner as other IBMs. The formation of complexes between the eicosanoids and the IBMRC is one preferred method of bringing about their removal from a contact lens surface.

The invention further relates to the contact lenses which have been modified in such a manner as to render them novel and unobvious. The invention relates to contact lenses previously exposed to proteins, lipoproteins, or lipids in the eye, having an eicosanoid concentration on the lens which is about

50% by weight or less than the concentration of eicosanoids on the lens before treatment. Preferably, the concentration is about 25% by weight or less than the concentration of eiconsanoids on the lens before the treatment . It is not possible to provide maximum acceptable quantitative concentrations of eicosanoids on a contact lens which is applicable to all eicosanoids. This is because different eicosanoids have widely varying acceptable concentrations. For example, prostaglandin E ₂ at 8 picograms per lens, and preferably at 4 picograms per lens, has been determined to be an acceptable concentration of eicosanoid for comfortable wear by a contact lens user. For 12 (S) hydroxyeicosatetraenoic acid, 4 nanograms, and preferably 2 nanograms, per lens has been found acceptable. For 15- hydroxyeicosatetraenoic acid, 14 picograms, preferably 7 picograms, per lens has been found acceptable. In a preferred embodiment, the above figures represent an eicosanoid by weight concentration of about 10% or less of the eicosanoids present on the lens before treatment.

In one embodiment, the composition, in particular the liquid aqueous medium, is substantially free of an oxidative disinfectant component. A contact lens can be contacted with the IBMRC without also contacting the lens with a disinfectant component.

In a preferred aspect, the present compositions are substantially free of an enzyme component that can remove proteinaceous material from the contact lens. Accordingly, compositions and methods of the invention can be used to clean contact lenses when provided in cleaning kits as solid articles, for example, tablets, or in liquid aqueous media, such as solutions. For instance, the compositions can substitute for weekly protein removal tablets.

The compositions can be used in combination with disinfectants, detergents, lubricants, wearability

components, other contact lens care components, and the like, for example, in aqueous solutions. A particularly attractive feature of the invention is that, in many instances, chemical disinfectants, such as hydrogen peroxide, chlorine dioxide and substantially non-oxidative disinfectants, can be in intimate contact with the IBMRC of the composition without significant decomposition of either component . The present invention can afford both disinfecting and treating of contact lenses in a single composition or method step.

The present compositions may comprise a disinfectant component. In one embodiment, the disinfectant component is present in the liquid aqueous medium in a substantially constant amount, that is, the concentration of the disinfectant component does not vary substantially with time, such as if it were incompatible with other components or were in the process of being destroyed, such as in the case of hydrogen peroxide in the presence of catalase or other hydrogen peroxide destroying components. The amount of the disinfectant component present in the liquid aqueous medium is effective to disinfect a contact lens placed in contact with the composition. When a disinfecting component is desired to be included in an instant composition, it may be an oxidative disinfectant component or a substantially non-oxidative disinfectant component. Oxidative disinfectant components act to reduce the microbial load on a contact lens by oxidatively attacking the microbes . The oxidative disinfectant suitable for use in the present invention is preferably selected from hydrogen peroxide, chlorine dioxide, metal, such as alkali metal, peroxy salts, such as peroxymonosulfate salts, and the like and mixtures thereof.

As used herein, substantially non-oxidative disinfectant components include effectively non-

oxidative organic chemicals which derive their antimicrobial activity through a chemical or physicochemical interaction with the microbes or microorganisms. Suitable non-oxidative disinfectant components are those generally employed in ophthalmic applications and include, but are not limited to, quaternary ammonium salts used in ophthalmic applications such as poly[dimethylimino-2-butene-l, 4- diyl] chloride, alpha- [4-tris (2-hydroxyethyl) ammonium] -dichloride (chemical registry number 75345- 27-6, available under the trademark Polyquaternium 1 ^® from Onyx Corporation) , benzalkonium halides, and biguanides such as salts of alexidine, alexidine-free base, salts of chlorhexidine, hexamethylene biguanides and their polymers, antimicrobial polypeptides, and the like and mixtures thereof. A particularly useful substantially non-oxidative disinfectant component is selected from tromethamine (2-amino-2-hydroxymethyl-l, 3 propanediol) and its ophthalmically acceptable salts alone or in combination with a microbicide component selected from polyhexa ethylene biguanide (PHMB) , N- alkyl-2-pyrsolidone, chlorhexidine, Polyquarternium-1, hexetidine, bronopol, alexidine, very low concentrations of peroxide, ophthalmically acceptable salts thereof and mixtures thereof.

The salts of alexidine and chlorhexidine can be either organic or inorganic and are typically disinfecting gluconates, nitrates, acetates, phosphates, sulfates, halides and the like. Generally, the hexamethylene biguanide polymers, also referred to as polyaminopropyl biguanide (PAPB) , have molecular weights of up to about 100,000. Such compounds are known and are disclosed in U.S. Patent No. 4,758,595.

The substantially non-oxidative disinfectant components useful in the present invention are preferably present in the liquid aqueous medium in

concentrations in the range of about 0.00001% to about 2% (w/v) .

More preferably, the substantially non-oxidative disinfectant component is present in the liquid aqueous medium at an ophthalmically acceptable or safe concentration such that the user can remove the disinfected lens from the liquid aqueous medium and thereafter directly place the lens in the eye for safe and comfortable wear. When a contact lens is desired to be disinfected by a disinfectant component, an amount of disinfectant effective to disinfect the lens is used. Preferably, such an effective amount of the disinfectant reduces the microbial burden on the contact lens by one log order, in three hours. More preferably, an effective amount of the disinfectant reduces the microbial load by one log order in one hour. Particularly preferred are disinfectant concentrations that reduce the microbial load by one log order in ten minutes or less. The disinfectant component in accordance with the present invention is preferably provided in the liquid aqueous medium, and is more preferably soluble in the liquid aqueous medium.

As an alternate to the use of chemical disinfectants, the contact lens may be thermally disinfected, for example, while in a liquid aqueous medium containing an IBMRC, as described herein. Subjecting a contact lens to elevated temperatures, for example, on the order of about 60°C to about 100°C, for a period of time, for example, on the order of about

0.3 hours to about 2 hours or more, is effective to disinfect the lens.

In one embodiment, the release of the IBMRC in the liquid aqueous medium can be delayed by the use of a delayed release or barrier component. Such delayed release of the IBMRC is useful in applications in which the removal component is incompatible with one or more

other components in the liquid aqueous medium. For example, certain substantially non-oxidative disinfectant components, such as hexamethylene biguanides and their polymers, used to disinfect contact lenses may react with, and/or become deactivated by, the ionically charged IBM removal components. Therefore, in order to avoid this and to obtain both effective disinfecting and cleaning of the contact lens, the IBMRC can be provided in a delayed release form. The release of the IBMRC is delayed a sufficient period of time so that the incompatible component, for example, the substantially non-oxidative disinfectant component, can perform its function, for example, disinfect the contact lens, before the IBMRC is released in the liquid medium to perform its function.

The barrier component may be provided by coating a core tablet, pill, granules or other particle or particles or the like, containing the IBMRC with a slow dissolving coating material, which may ultimately be completely or only partially soluble in the liquid aqueous medium. The delayed exposure form of the IBMRC is preferably such that substantially no effective exposure of the IBMRC to the liquid aqueous medium occurs during the delay period followed by rapid and substantially complete exposure of the IBMRC at the end of or after the delay period.

Barrier components suitable as either coatings or as matrices, include water soluble vinyl polymers, such as polyvinylpyrrolidone, polyvinylalcohol and polyethyleneglycol; water soluble proteins; polysaccharide and cellulose derivatives, such as methyl cellulose, hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose; alginic acid and its salts and other derivatives; and the like and mixtures thereof. 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 which may be employed to provide for delayed exposure of the enteric polymeric component is well known in the art as exemplified by the text Controlled Drucf Delivery, 2nd Ed., Joseph R. Robinson & Vincent H.L. Lee, Eds., Marcel Dekker, Inc., New York, 1987.

The amount of barrier components used is not critical in the present invention provided that such barrier component functions as described herein. The barrier component or components may suitably be present in the range of about 1% or about 5% to about 1000% or more, based on the weight of the IBMRC.

The present solid compositions may be produced using any one of many suitable methods, a number of which are conventional and well known in the art. The production method chosen depends, in large measure, on the desired form of the composition. For example, the solid component can be molded or cut or otherwise shaped into the desired form.

The present compositions may further comprise effective amounts of one or more additional components, such as an additional cleaning component, for example, a detergent component, an enzyme component and the like; a conditioning component; a wetting component; a wearability component, a buffer component, a tonicity adjustor component; a chelating or sequestering agent, such as the disodium salt of ethylenediamine tetraacetic acid (EDTA) and the like and mixtures thereof. The additional component or components may be selected from materials which are known to be useful in contact lens care compositions and are included in amounts effective to provide the desired effect or benefit. When an additional component is included, it is preferably compatible under typical use and storage conditions with the other components of the composition. For instance, when a disinfectant

component is provided, the aforesaid additional component or components are preferably substantially stable in the presence of the disinfectant.

Each of the additional components, if any, may be present in either the solid or liquid form of the present compositions. When the additional component or components are present as a solid, they can either be intimately admixed such as in a powder or compressed tablet or they can be substantially separated, although in the same particles, as in an encapsulated pellet or tablet. When the combination of IBMRC and additional component or components is in liquid form, they are typically soluble in the liquid aqueous medium. One or both of the IBMRC and the additional component or components can be in solid form until desired to be used, whereupon they can be dissolved in the liquid aqueous medium in order to effectively contact the surface of a contact lens.

When an additional cleaning component is included in the present compositions, the cleaning component should be present in an amount effective to at least facilitate removing debris from a contact lens. Exemplary cleaning components include detergents such as nonionic surfactants, for example, polysorbates (such as polysorbate 20-Tradename Tween 20) , ethylene oxide/ propylene oxide block copolymers, glycolic esters of fatty acids and the like, anionic surfactants, for example, alkyl ether sulfates and the like, and mixtures thereof. Cleaning enzymes may also be employed. A cleaning enzyme component can be provided in an amount effective to at least facilitate removing deposit material from the contact lens. Types of deposit material or debris which may be deposited on the lens include proteins, lipids, and carbohydrate-based or mucin-based debris. One or more types of debris may be present on a given lens .

The cleaning enzyme component employed may be selected from enzymes conventionally employed in the enzymatic cleaning of contact lenses. Among the preferred enzymes are proteases, lipases, and the like. Exemplary enzymes are described by Huth et al U.S. Patent No. RE 32,672 and Karageozian et al U.S. Patent No. 3,910,296, which disclosures are incorporated herein by reference.

Preferred proteolytic enzymes are those substantially free of sulfhydryl groups or disulfide bonds, the presence of which may react with active oxygen of the oxidative disinfectant, rendering the enzyme inactive. Metalloproteases, enzymes which contain a divalent metal ion, may also be used. Yet a more preferred group of proteolytic enzymes are the serine proteases, such as those derived from Bacillus and Streptomyces bacteria and Aspercrillus molds. Of this class of enzymes, still more preferred enzymes are those derived from alkaline proteases, generically referred to as subtilisin enzymes.

Other enzymes preferred for this application include pancreatin, trypsin, collagenase, keratinase, carboxylase, aminopeptidase, elastase, and aspergillopeptidase A and B, pronase E (from S_;_ crriseus) and dispase (from Bacillus polymyxa) .

In one embodiment, a liquid aqueous medium containing such a cleaning enzyme component preferably has sufficient enzyme to provide about 0.001 to about 3 Anson units of activity, more preferably about 0.01 to about 1 Anson units, per single lens treatment.

However, higher or lower amounts may be used. Moreover, since enzyme activity is pH dependent, the preferred pH range for an enzyme can be determined by the skilled practitioner. A particularly noteworthy embodiment of the present compositions is substantially free of proteolytic enzyme. Such a formulation provides for

effective contact lens cleaning without the need to rinse the lens after cleaning to free the lens of the enzyme.

Compositions of the invention can also include preservatives, stabilizers, color indicators of hydrogen peroxide decomposition, plasticizers, thickening agents and the like.

Acceptable effective concentrations for these additional components in the compositions of the invention are readily apparent to the skilled practitioner.

The liquid aqueous medium used is selected to have no substantial deleterious effect on the lens being treated, or on the wearer of the treated lens. The liquid medium is constituted to permit, and even facilitate, the instant lens treatment or treatments. The liquid aqueous medium is preferably substantially isotonic or hypertonic (for example, slightly hypertonic) and/or ophthalmically acceptable. The liquid aqueous medium preferably includes an effective amount of a tonicity adjusting component to provide the liquid medium with the desired tonicity. The liquid aqueous medium of the present invention preferably includes a buffer component which is present in an amount effective to maintain the pH of the medium in the desired range. Such tonicity adjusting components and buffer components may be present in the liquid aqueous medium and/or may be introduced into the liquid aqueous medium. Among the suitable tonicity adjusting components that may be employed are those conventionally used in contact lens care products, such as various inorganic salts. Sodium chloride and the like are very useful tonicity adjusting components. Among the suitable buffer components or buffering agents that may be employed are those conventionally used in contact lens care products. The buffer salts are preferably alkali metal, alkaline earth metal, or

ammonium salts. Particularly useful media are those derived from saline, e.g., a conventional saline solution, or buffered saline solution. In addition, the liquid aqueous media may include one or more other materials, for example, as described elsewhere herein, in amounts effective to treat the contact lens (for example, provide a beneficial property to the contact lens) contacted with such media.

In the event an oxidative disinfectant component is employed, a disinfectant destroying component is preferably also employed. Any agent effective in destroying the oxidative disinfectant used can be employed as the disinfectant destroying component . Such a disinfectant destroying component should be used in an amount effective to destroy substantially all the oxidative disinfectant present in the liquid aqueous medium during a reasonable period of time. The disinfectant destroying component employed should have no undue detrimental effect on the contact lens or on a wearer's eye when the lens is placed therein. Particularly useful disinfectant destroying components include reducing agents, enzymes, such as peroxidases, for example, catalase, and mixtures thereof.

Exemplary reducing agents include those effective to chemically reduce hydrogen peroxide. Such reducing agents include thiosulfates, thiourea, sulfites, thioglycerol, N-acetylcysteine, formates, ascorbic acid, isoascorbic acid, glyoxylic acid and mixtures thereof. Especially preferred are alkali metal salts of the above compounds. Peroxidases, that is enzymes that promote the decomposition of hydrogen peroxide, can also be employed. A particularly preferred peroxidase is catalase. When catalase is employed as a disinfectant destroying component, a useful amount of catalase for a liquid aqueous medium containing about 3% (w/v) hydrogen peroxide is preferably about 10 to about 1000, more preferably about 20 to about 800,

international units of catalase activity per milliliter of liquid aqueous medium.

If a disinfectant destroying component is employed, it may be provided in a delayed release form, for example, in one or more solid articles in combination with a delayed release or barrier component as described elsewhere herein. The release of the disinfectant destroying component is preferably delayed a sufficient time, for example, on the order of about 0.1 hour to about 2 hours or more, to allow the oxidative disinfectant component to disinfect a contact lens placed in the liquid aqueous medium containing the oxidative disinfectant component at substantially the same time the disinfectant destroying component is initially contacted with the liquid aqueous medium.

Methods for cleaning a contact lens using the herein described compositions are included within the scope of the invention. Such methods comprise contacting a contact lens with such a composition at conditions effective to remove proteinaceous deposit material from the contact lens.

The contacting temperature is preferred to 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 in the range of about 5 minutes or about 1 hour to about 12 hours or more.

The contact lens can be contacted with the liquid aqueous medium by immersing the lens in the medium. During at least a portion of the contacting, the liquid medium containing the contact lens can be agitated, for example, by shaking the container containing the liquid aqueous medium and contact lens, to at least facilitate

removal of deposit material from the lens. After such contacting step, the contact lens may be manually rubbed to remove further deposit material from the lens. The cleaning method can also include rinsing the lens substantially free of the liquid aqueous medium prior to returning the lens to a wearer's eye.

When the IBMRC is an ophthalmically acceptable material, and other components of the composition, if any, are also ophthalmically acceptable, the IBMRC can be added directly to the eye containing the lens to be treated, such as in the form of eye drops. After the lens has been cleaned, other rinsing eyedrops can optionally be added.

Alternatively, the lens can be removed from the eye, and the liquid containing the IBMRC can be applied to the lens and wiped or rubbed with a tissue or other lint free applicator, and then reinserted in the eye.

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

EXAMPLE 1 A buffered saline solution is made which contains the following components in percent by weight: 0.60% sodium chloride, 0.39% boric acid, 0.20% sodium borate decahydrate in purified water. The solution is adjusted to pH 7.4 with sodium hydroxide and hydrochloric acid. A suspension is made by hydrating 0.1 g of hydroxyalkoxy-propyl Dextran particles and mixing the hydrated particles with 10 ml of the buffered saline solution. Alternatively, δ>-aminodecyl Agarose or trimethylamino Sepharose is substituted for the hydroxyalkoxypropyl Dextran.

EXAMPLE 2 An aqueous solution is prepared which contains albumin from bovine serum which has been treated with charcoal to remove fatty acids. The solution contains

the following components in percent by weight: 1.0% albumin, 0.60% sodium chloride, 0.39% boric acid, 0.20% sodium borate decahydrate in purified water. The solution is adjusted to pH 7.4 with sodium hydroxide and hydrochloric acid.

EXAMPLE 3

An aqueous solution is made which contains the following components in percent by weight: 0.01% methyl-/3-cyclodextrin, 0.60% sodium chloride, 0.39% boric acid, 0.02% sodium borate decahydrate in purified water. The solution is adjusted to pH 7.4 with sodium hydroxide and hydrochloric acid.

EXAMPLE 4

An emulsion is prepared by shaking 5 ml castor oil with 5 ml buffered saline at room temperature. Alternatively, cottonseed oil, olive oil, or mineral oil is substituted for the castor oil.

EXAMPLE 5

The composition of Example 1, 2, 3 or 4 is combined with a nonionic surfactant, for example polysorbate 80, with a non-oxidative antimicrobial, for example, polyhexamethylene biguanide, and/or with a rigid contact lens care solution.

EXAMPLE 6

An IBM deposit laden contact lens is added to a vial containing 10 ml of a suspension, solution, or emulsion as described in the Examples 1, 2, 3, 4 or 5. The contact lens is maintained in this treatment liquid at room temperature for 10 hours. Alternatively, the contact lens is maintained in this treatment liquid at room temperature and the vial is shaken after 5 hours and at the end of the 10 hour period which facilitates dislodging deposit material from the lens. After the

10 hour period the lens is removed from the treatment liquid and placed in the lens wearer's eye for safe and comfortable wear. Alternatively, after the 10 hour period of time, the lens is removed from the treatment liquid and rinsed with an additional quantity of the buffered saline solution before being placed in the lens wearer's eye for safe and comfortable wear. Alternatively, after the 10 hour period of time the lens is removed from the treatment liquid, manually rubbed and rinsed with an additional quantity of the buffered saline solution before being placed in the lens wearer's eye for safe and comfortable wear. It is found that a substantial portion of the IBM deposits previously present on the lens has been removed. These examples of lens cleaning methods may be followed by the use of existing lens care solutions, such as disinfecting, proteolytic cleaning, rewetting, or lubricating solutions.

EXAMPLE 7

A tablet having the following composition is prepared by compressing a mixture of powders having the same chemical make-up using conventional compression tableting techniques: Hydroxyalkoxypropyl Dextran 0.1 g

Sodium Chloride 60 mg

Boric Acid 40 mg

Sodium Borate Decahydrate 20 mg

The ingredients are mixed and pressed into a tablet.

EXAMPLE 8

A tablet having the following composition is prepared by compressing a mixture of powders having the same chemical make-up using conventional compression

tableting techniques :

Bovine Serum albumin 0.1 g

Methyl-/S-Cyclodextrin 1 mg

Sodium Chloride 60 mg Boric Acid 40 mg

Sodium Borate Decahydrate 20 mg

The ingredients are mixed and pressed into a tablet.

EXAMPLE 9

A tablet similar to that described in Example 7 or

8 is produced except that the tablet includes a delayed release coating having the following composition:

Hydroxypropylmethyl cellulose 5 mg Triethylcitrate (a plasticizer) 0.5 mg

This coating is applied using conventional techniques.

EXAMPLE 10 A tablet prepared as in example 7, 8 or 9 is added to a vial containing 10 ml of purified water and the IBM deposit laden contact lens. The tablet dissolves in the solution and the pH is approximately neutral. The contact lens is maintained in this solution at room temperature for 10 hours. Alternatively, the contact lens is maintained in this solution at room temperature and the vial is shaken after 5 hours and at the end of the 10 hour period which facilitates dislodging deposit material from the lens. After the 10 hour period the lens is removed from the solution and placed in the lens wearer's eye for safe and comfortable wear. Alternatively, after the 10 hour period of time, the lens is removed from the solution and rinsed with an additional quantity of the buffered saline solution before being placed in the lens wearer's eye for safe and comfortable wear. Alternatively, after the 10 hour period of time the lens is removed from solution, manually rubbed and rinsed with an additional quantity of the buffered saline solution before being placed in the lens wearer's eye for safe and comfortable wear.

It is found that a substantial portion of the IBM deposits previously present on the lens has been removed. These examples of lens cleaning methods may be followed by the use of existing lens care solutions, such as disinfecting, proteolytic cleaning, rewetting, or lubricating solutions.

EXAMPLE 11

Example 10 is repeated except that the solution further includes an effective amount of a nonionic surfactant, such as 0.1% by weight polysorbate 80.

EXAMPLE 12

Example 10 is repeated except that the solution further includes an effective amount of a nonoxidative antimicrobial, such as 0.01% by weight polyhexamethylene biguanide.

EXAMPLE 13 Example 10 is repeated except that the tablet is added to a conventional rigid contact lens care solution, such as the product sold by Allergan, Inc. under the trademark, Wet-N-Soak Plus™.

EXAMPLE 14

A two (2) layer tablet, having a core tablet surrounded by a coating, is prepared for testing. The core tablet and coating have the following compositions : CORE TABLET:

Crystalline Catalase ⁽¹⁾ 1.5 mg

Bovine serum albumin 0.1 g

Methyl-jS-Cyclodextrin 1 mg

Sodium Chloride 60 mg Boric Acid 40 mg

Sodium Borate Decahydrate 20 mg

COATING:

Hydroxypropylmethyl 5 mg cellulose phthalate ⁽¹⁾ The tablet contains about 5200 units of catalase activity.

10 ml of an aqueous solution containing 3% (w/v) of hydrogen peroxide is introduced into a vial containing an IBM deposit laden contact lens. At substantially the same time, the above-noted tablet is introduced into the vial. After 30 minutes, the tablet dissolved in the solution. The contact lens is maintained in this solution at room temperature for 10 hours. Alternatively, the contact lens is maintained in this solution at room temperature and the vial is shaken after 5 hours and at the end of the 10 hour period which facilitates dislodging deposit material from the lens. After the 10 hour period the lens is removed from the solution and placed in the lens wearer's eye for safe and comfortable wear. Alternatively, after the 10 hours period of time, the lens is removed from the solution and rinsed with an additional quantity of the buffered saline solution before being placed in the lens wearer's eye for safe and comfortable wear. Alternatively, after the 10 hour period of time the lens is removed from solution, manually rubbed and rinsed with an additional quantity of the buffered saline solution before being placed in the lens wearer's eye for safe and comfortable wear. It is found that a substantial portion of the IBM deposits previously preset on the lens has been removed. These examples of lens cleaning methods may be followed by the use of existing lens care solutions, such as disinfecting, proteolytic cleaning, rewetting, or lubricating solutions.

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.