Contact lens treatment solution

Abstract

The contact lens treatment solution comprises: (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate; (b) an antimicrobial agent comprising alexidine or a salt or free base thereof; and (c) optionally, one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate, wherein, when one or more sodium salts are present, the one or more potassium salts are present in an amount greater than the amount of the one or more sodium salts.

Description

[Technical Field]

[0001] Priority This application claims priority to U.S. Provisional Patent Application No. 63 / 434,601, entitled "Contact Lens Treatment Solution," filed December 22, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Contact lenses are being used by an increasing number of people as a means of correcting vision and / or compensating for ocular abnormalities, but contact lenses typically must be worn and removed daily, requiring sterile solutions and containers for cleaning and disinfecting between wears.

[0003] During contact lens wear and normal handling, not only microorganisms but also biological molecules such as lipids and proteins can adhere to contact lenses and contaminate the solution and / or storage container. Furthermore, the tear film, which contains proteins, lipids, and even microorganisms, can coat the ocular surface. These components present in the tear film, the outer surface of the eye, or the surrounding skin can be carried into the contact lens solution and / or storage container. Microorganisms that grow in the solution and / or storage container can then be transferred to the eye via the contact lens, where they can become pathogens and cause eye infections that can lead to vision loss and blindness. Various solutions have been developed to remove these deposits and kill microorganisms. Summary of the Invention

[0004] According to an exemplary embodiment, there is provided a contact lens treatment solution, said treatment solution comprising:

[0005] (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate;

[0006] (b) an antibacterial agent comprising alexidine or a salt or free base thereof;

[0007] (c) optionally, one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate, wherein the one or more potassium salts are present in an amount greater than the amount of the one or more sodium salts, if present.

[0008] According to another exemplary embodiment, there is provided a method of cleaning and disinfecting contact lenses, said method comprising immersing a contact lens in a contact lens treatment solution for a time sufficient to clean and disinfect the contact lens, wherein the contact lens treatment solution comprises:

[0009] (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate;

[0010] (b) an antibacterial agent comprising alexidine or a salt or free base thereof;

[0011] (c) optionally, one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate, wherein the one or more potassium salts are present in an amount greater than the amount of the one or more sodium salts, if present.

[0012] According to yet another exemplary embodiment, there is provided a method for inhibiting bacterial adhesion to a surface of a contact lens, said method comprising contacting the surface of the contact lens with a contact lens treatment solution, said treatment solution comprising:

[0013] (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate;

[0014] (b) an antibacterial agent comprising alexidine or a salt or free base thereof;

[0015] (c) optionally, one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate, wherein the one or more potassium salts are present in an amount greater than the amount of the one or more sodium salts, if present. DETAILED DESCRIPTION OF THE INVENTION

[0016] Exemplary embodiments described herein are directed to contact lens treatment solutions for cleaning, rinsing, storing, and disinfecting contact lenses. For example, "daily cleaners" containing various surfactants and disinfectants are recommended for daily use to remove most deposits and debris from contact lenses. As an approach to preventing protein deposition, contact lens treatment solutions containing chemical agents, such as cationic polymers, have been developed to prevent protein deposition on the lens surfaces of rigid gas permeable (RGP) and soft contact lenses. Furthermore, solutions for wetting lenses before placement on the eye are often required for both hard and soft contact lenses, although their formulations tend to differ based on the lens's characteristics. After the contact lenses are placed on the eye, eye drops for rewetting, lubrication, and / or improving the wearer's comfort can be administered to the eye via an eyedropper.

[0017] Multi-purpose solutions are popular due to the convenience of being able to clean, disinfect, and condition contact lenses with a single solution immediately before placing them in the eye. Multi-purpose solutions are designed to be usable as wetting agents without rinsing, which means they must be ophthalmologically safe for eye contact. Therefore, the types and concentrations of cleaning agents and biocides that tend to irritate the eyes when used in the solution as preservatives or disinfectants are somewhat limited. Furthermore, surfactants must not interfere with the wetting or conditioning functions of the solution. Various solutions have been developed to remove these deposits and kill microorganisms. However, improvements in solutions for removing these deposits and killing microorganisms remain a challenge.

[0018] The exemplary embodiments described herein are directed to an improved contact lens treatment solution for cleaning, rinsing, storing, and disinfecting contact lenses. While various features of the composition are described in the context of a single embodiment for brevity, they may also be provided separately or in any suitable subcombination. All combinations of the embodiments are specifically embraced in the exemplary embodiments disclosed herein, just as if each and every combination were individually and expressly disclosed. Furthermore, all subcombinations listed in the embodiments describing such variations are also specifically embraced in the compositions of the present invention, and are disclosed herein, just as if each and every such subcombination were individually and expressly disclosed herein.

[0019] A contact lens treatment solution according to non-limiting exemplary embodiments disclosed herein comprises at least (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate; (b) an antimicrobial agent comprising alexidine or a salt or free base thereof; and (c) optionally, one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate, wherein the one or more potassium salts are present in an amount greater than the amount of the one or more sodium salts, if present.

[0020] Thus, the first component of the contact lens treatment solutions disclosed herein includes one or more potassium salts, such as, for example, potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate (e.g., mono-, di-, tripotassium, and tetra-potassium salts), and potassium phosphate, in non-limiting exemplary embodiments.

[0021] In exemplary embodiments, the one or more potassium salts are present in the contact lens treatment solution in an amount of about 0.02 to about 1.5 wt.%, based on the total weight of the contact lens treatment solution. In other embodiments, the one or more potassium salts are present in the contact lens treatment solution in an amount of about 0.05 to about 0.9 wt.%, based on the total weight of the contact lens treatment solution.

[0022] The second component of the contact lens treatment solution disclosed herein includes alexidine, or a salt or free base thereof, as an antibacterial / disinfecting agent. As those skilled in the art will readily appreciate, alexidine is a non-polymeric biguanide, also known as 1,1'-hexamethylene-bis[5-(2-ethylhexyl)biguanide]. In exemplary embodiments, alexidine is present as alexidine itself, a salt of alexidine (e.g., alexidine HCl), alexidine free base, or a mixture thereof. The alexidine salt may be organic or inorganic, and is typically a disinfecting nitrate, acetate, phosphate, sulfate, halide, or the like.

[0023] In exemplary embodiments, alexidine is present in the contact lens treatment solution in an amount of about 0.0001 to about 0.0006 wt.%, based on the total weight of the contact lens treatment solution. In another embodiment, alexidine is present in the contact lens treatment solution in an amount of about 0.0002 to about 0.0003 wt.%, based on the total weight of the contact lens treatment solution.

[0024] In a non-limiting embodiment, the contact lens treatment solutions disclosed herein may optionally include one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate. When one or more of these sodium salts are present in the contact lens treatment solution, the one or more potassium salts are present in an amount greater than the amount of the one or more sodium salts, if present.

[0025] In an exemplary embodiment, the one or more sodium salts are present in the contact lens treatment solution in an amount of about 0.01 to about 1 wt. %, based on the total weight of the contact lens treatment solution.

[0026] In one or more additional non-limiting exemplary embodiments that can be combined with one or more of the preceding paragraphs, the contact lens treatment solutions disclosed herein may include, in addition to alexidine, other non-polymeric biguanides. For example, in exemplary embodiments, in addition to alexidine, the other non-polymeric biguanides include chlorhexidine, salts of chlorhexidine, and the like, and mixtures thereof. The chlorhexidine salts may be organic or inorganic, and are typically disinfecting nitrates, acetates, phosphates, sulfates, halides, and the like. The additional non-polymeric biguanides may be present in the contact lens treatment solution in amounts similar to the amount of alexidine, e.g., about 0.0001 to about 0.0006 wt.%, based on the total weight of the contact lens treatment solution.

[0027] In one or more additional non-limiting exemplary embodiments that can be combined with one or more of the preceding paragraphs, the contact lens treatment solution may further comprise one or more additional antimicrobial / disinfecting agents. In non-limiting exemplary embodiments, the one or more additional antimicrobial / disinfecting agents include one or more polyquaternium polymers, or salts or free bases thereof. One or more polyquaternium polymers suitable for use herein include polyquaternium polymers having from about 30 to about 50,000 quaternary amine functional repeating units. In one exemplary embodiment, at least one polyquaternium polymer may have from about 50 to about 2,000 quaternary amine functional repeating units. As used herein, "quaternary amine functional repeating unit" is understood to mean that the repeating unit comprises a quaternary amine group in which a positively charged nitrogen atom is covalently bonded to four radicals (no hydrogen atoms) and ionically bonded to a negatively charged counterion, such as chloride.

[0028] The one or more polyquaternium polymers may have a weight average molecular weight, Mw, of about 3,000 to about 5,000,000. In one exemplary embodiment, at least one polyquaternium polymer may have a weight average molecular weight, Mw, of about 5,000 to about 500,000. In another exemplary embodiment, the one or more polyquaternium polymers may have a weight average molecular weight, Mw, of about 5,000 to about 200,000. In another exemplary embodiment, the one or more polyquaternium polymers may have a weight average molecular weight, Mw, of about 5,000 to about 50,000. In one exemplary embodiment, the one or more polyquaternium polymers may have a weight average molecular weight, Mw, of about 5,000 to about 30,000. In another exemplary embodiment, the one or more polyquaternium polymers may have a weight average molecular weight, Mw, of about 18,000 to about 24,000.

[0029] In non-limiting exemplary embodiments, polyquaternium polymers useful herein may include copolymers in which the quaternary amine functional repeat units are derived from one or more of the following types of monomers: N,N-dimethyl-N-ethyl-aminoethyl acrylate and methacrylate, 2-methacryloxyethyltrimethylammonium, N-(3-methacrylamidopropyl)-N,N,N-trimethylammonium, 1-vinyl and 3-methyl-1-vinylimidazole, N-(3-acrylamido-3-methylbutyl)-N,N,N-trimethylammonium, N-(3-methacryloyloxy-2-hydroxypropyl)-N,N,N-trimethylammonium, halide or other salt forms thereof, and derivatives thereof involving substitution, addition, or removal of alkyl groups, e.g., alkyl groups having 1 to 6 carbon atoms. Quaternary amine-functional repeating units can also be obtained as a reaction product or two or more compounds by using a strong alkylating agent such as 1,4-dichloro-2-butene, which can be reacted with, for example, 1,4-bis[dimethylamino]-2-butene and triethanolamine to produce a polymeric polyquaternary ammonium compound. Quaternary amine-functional repeating units can also be prepared from other polymers, for example, by reacting trimethylammonium-substituted epoxides with the hydroxy groups of hydroxyethyl cellulose.

[0030] Suitable quaternary amine functional repeat units also include those present in polymeric ionenes formed by polycondensation reactions, in which the quaternary amine nitrogen is integral to the polymer backbone and located between alkylene, oxyalkylene, or other segments.

[0031] In an exemplary embodiment, the nitrogen in the quaternary amine-functional repeat unit is part of a saturated or unsaturated heterocyclic ring, e.g., a five- or six-membered ring. In one embodiment, the polyquaternium polymer is a copolymer of vinylimidazolium salt or dimethyldiallylammonium salt. In one embodiment, up to about 90 mol %, e.g., about 40% to about 90 mol %, of a copolymerizable comonomer lacking quaternary amine functionality can be copolymerized with the quaternary amine-functional comonomer. Suitable comonomers include, for example, vinylpyrrolidone, acrylic acid, alkyl methacrylates, amides and amines (e.g., acrylamide, N,N-dialkylaminoalkyl acrylates and N,N-dialkylaminoalkyl methacrylates), hydroxyethyl cellulose, and copolymerizable mixtures thereof. In one embodiment, the alkyl group has 1 to 6 carbon atoms.

[0032] Polyquaternium polymers, as defined above, are a well-known class of polymers, and many variations are commercially available. For example, the latest CTFA International Cosmetic Ingredient Dictionary lists polyquaterniums designated as Polyquaternium-1 through Polyquaternium-68, many of which are useful in the exemplary embodiments disclosed herein based on the teachings of the present invention. Polymerization techniques for preparing such materials are similarly well known to those skilled in the art, and many variations of such techniques are similarly commercially practiced. New variations of such polyquaternium polymers are continually being commercially developed; for example, various polymers having different combinations of identical or similar repeating units, different relative proportions of comonomers, and / or different molecular weights are continually being commercially developed.

[0033] In one embodiment, the polyquaternium polymer is polyquaternium-1. Polyquaternium-1 is commercially available from sources such as Stepan Inc. under the trademark Onamer® M, or can be synthesized by known methods. See, e.g., U.S. Pat. No. 4,027,020, the contents of which are incorporated herein by reference. Optionally, the polymer may have alternative end groups, such as hydroxyallyl end groups, aminoallyl end groups, and diene end groups. See, e.g., U.S. Pat. No. 7,705,112, the contents of which are incorporated herein by reference.

[0034] The one or more polyquaternium polymers suitably comprise an ophthalmologically suitable anionic organic or inorganic counterion. In an exemplary embodiment, the preferred counterion is chloride.

[0035] In certain embodiments, the cationic oligomer or polymer is characterized by a charge density, which can be measured by methods known in the art, such as colloid titration. In one embodiment, the charge density of the cationic oligomer or polymer is at least about 0.1 meq / g, in another embodiment at least about 2.5 meq / g, and in yet another embodiment at least about 5 meq / g.

[0036] In exemplary embodiments, the one or more polyquaternium polymers are present in the contact lens treatment solution in an amount of about 0.00005 to about 0.0003 wt.%, based on the total weight of the contact lens treatment solution. In other embodiments, the one or more polyquaternium polymers are present in the contact lens treatment solution in an amount of about 0.0001 to about 0.0002 wt.%, based on the total weight of the contact lens treatment solution.

[0037] Additional antimicrobial / disinfecting agents that can be used in the contact lens treatment solutions disclosed herein include, for example, polymeric biguanides or salts or free bases thereof, terpenes or derivatives thereof, branched glycerol monoalkyl ethers, branched glycerol monoalkyl amines, branched glycerol monoalkyl sulfides, fatty acid monoesters containing an aliphatic fatty acid moiety and an aliphatic hydroxyl moiety having 6 to 14 carbon atoms, amidoamine compounds, and combinations thereof.

[0038] Suitable polymeric biguanide antibacterial agents include, for example, polymeric hexamethylene biguanide (PHMB) (commercially available from Zeneca, Wilmington, Delaware), and polymers and water-soluble salts thereof. In one embodiment, the water-soluble polymeric biguanides used herein may have a number-average molecular weight of at least about 1,000, or from about 1,000 to about 50,000. Suitable water-soluble salts of the free base include, for example, hydrochloride, borate, acetate, gluconate, sulfonate, tartrate, and citrate. Hexamethylene biguanide polymers, also known as polyaminopropyl biguanide (PAPB), generally have a number-average molecular weight of up to about 100,000. Such compounds are known and are disclosed in U.S. Pat. No. 4,758,595, the contents of which are incorporated herein by reference.

[0039] PHMB is best described as a polymeric biguanide composition comprising at least three, and preferably at least six, biguanide polymers, designated PHMB-A, PHMB-CG, and PHMB-CGA, whose general chemical structures are shown below. [ka] [ka] [ka]

[0040] For each of these polymers, "n" represents the average number of repeating groups. Each of the polymers shown has a distribution of polymer lengths. The traditional PHMB synthesis route provided a polymeric biguanide composition with PHMB-CGA (i.e., a cyanoguanidino end cap at one end and an amine at the other end) accounting for approximately 50 wt.% of the polymeric composition, approximately 25 wt.% of PHMB-A, and approximately 25 wt.% of PHMB-CG. Given the approximate weight ratios of the three major PHMB polymers, the proportion of cyanoguanidino end caps is also approximately 50% of the total number of end groups. In this application, this traditional polymeric biguanide composition is referred to as poly(hexamethylenebiguanide) or PHMB.

[0041] 13 Polymeric biguanide compositions having a terminal amine group content of less than about 18 mol% as measured by C NMR can also be used. The polymeric biguanide compositions are characterized by a relative increase in the molar concentration of terminal guanidine groups or terminal cyanoguanidino groups. For example, in one embodiment, the biguanide composition contains less than about 18 mol% terminal amine groups and greater than or equal to about 40 mol% terminal guanidine groups. In another embodiment, the biguanide composition contains less than about 18 mol% terminal amine groups and greater than or equal to about 55 mol% terminal guanidine groups.

[0042] The biguanide composition is PHMB-CG * Polymeric biguanide compositions, also known generically as "hexamethylene biguanides," are commonly referred to by those skilled in the art as PHMB and PHMB-CG. * It will be understood that this includes both.

[0043] Suitable terpene antimicrobial agents include, for example, monoterpenes, sesquiterpenes, and / or diterpenes, or derivatives thereof. Acyclic, monocyclic, and / or bicyclic monoterpenes, sesquiterpenes, and / or diterpenes, as well as those with a higher number of rings, can be used. As used herein, a "derivative" of a terpene should be understood to mean a terpene hydrocarbon having one or more functional groups, such as a terpene alcohol, terpene ether, terpene ester, terpene aldehyde, terpene ketone, or combinations thereof. Both trans and cis isomers are suitable. In one embodiment, the terpene moiety in the terpenes and derivatives may contain from 6 to about 100 carbon atoms, or from about 10 to about 25 carbon atoms.

[0044] Representative examples of suitable terpene alcohol antimicrobial agents include verbenol, trans-pinocarveol, cis-2-pinanol, nopol, isoborneol, carveol, piperitol, thymol, α-terpineol, terpinen-4-ol, menthol, 1,8-terpine, dihydroterpineol, nerol, geraniol, linalool, citronellol, hydroxycitronellol, 3,7-dimethyloctanol, dihydromyrcenol, tetrahydroalloocimenol, perillic alcohol, falcarindiol, and the like, and mixtures thereof.

[0045] Representative examples of suitable terpene ether and terpene ester antimicrobial agents include 1,8-cineole, 1,4-cineole, isobornyl methyl ether, rosopyran, α-terpinyl methyl ether, menthofuran, trans-anethole, methyl chavicol, allocimene diepoxide, limonene monoepoxide, isobornyl acetate, nonyl acetate, α-terpinyl acetate, linalyl acetate, geranyl acetate, citronellyl acetate, dihydro-terpinyl acetate, meryl acetate, and the like, and mixtures thereof.

[0046] Representative examples of terpene aldehyde and terpene ketone antimicrobial agents include myrtenal, campholenic aldehyde, perillaldehyde, citronellal, citral, hydroxycitronellal, camphor, verbenone, carbenone, dihydrocarvone, carvone, piperitone, menthone, geranyl acetone, pseudoionone, α-ionine, isopseudomethylionone, n-pseudomethylionone, isomethylionone, n-methylionone, and the like, and mixtures thereof. Any other terpene hydrocarbon having a functional group known in the art can be used in the compositions of the present invention.

[0047] In exemplary embodiments, suitable terpenes or derivatives thereof as antimicrobial agents include tricyclene, α-pinene, terpinolene, carveol, amyl alcohol, nerol, β-santalol, citral, pinene, nerol, β-ionone, caryophyllene (from clove), guaiol, anisaldehyde, cedrol, linalool, d-limonene (orange oil, lemon oil), longifolene, anisyl alcohol, patchouli alcohol, α-cadinene, 1,8-cineole, ρ-cymene, 3-carene, ρ-8-menthane, trans-menthone, borneol, α-fenchol, isoamyl acetate, terpiene, benzoyl benzoate ... Examples of oleic anhydrase inhibitors include, but are not limited to, cinnamaldehyde, ionone, geraniol (derived from flowers such as rose), myrcene (derived from bayberry wax, bay oil, and verbena oil), nerol, citronellol, carvacrol, eugenol, carvone, alpha-terpineol, anethole, camphor, menthol, limonene, nerolidol, farnesol, phytol, carotene (vitamin A1), squalene, thymol, tocotrienol, perillyl alcohol, borneol, cymene, carene, terpenes, linalool, 1-terpene-4-ol, zingiberene (derived from ginger), and the like, and mixtures thereof.

[0048] In an exemplary embodiment, a suitable branched glycerol monoalkyl ether antimicrobial agent is 3-[(2-ethylhexyl)oxy]-1,2-propanediol (EHOPD). In another embodiment, a suitable branched glycerol monoalkylamine antimicrobial agent is 3-[(2-ethylhexyl)amino]-1,2-propanediol (EHAPD). In another embodiment, a suitable branched glycerol monoalkyl sulfide antimicrobial agent is 3-[(2-ethylhexyl)thio]-1,2-propanediol (EHSPD). In yet another embodiment, the ophthalmic composition comprises any mixture of EHOPD antimicrobial agents, EHAPD antimicrobial agents, and EHSPD antimicrobial agents. The chemical structures of EHOPD, EHAPD, and EHSPD are shown below. [ka] [ka] [ka]

[0049] EHOPD, also known as octoxyglycerin, is sold under the trade name Sensiva® SC50 (Schulke & Mayr). EHOPD is a branched glycerol monoalkyl ether known to be gentle on the skin and to exhibit antibacterial activity against various Gram-positive bacteria, such as Micrococcus luteus, Corynebacterium aquaticum, Corynebacterium flavescens, Corynebacterium callunae, and Corynebacterium nephredi. Therefore, EHOPD is used in various skin deodorant formulations at concentrations of approximately 0.2-3 wt.%. EHAPD can be prepared from 2-ethylhexylthiol and 2,3-epoxy-1-propanediol using chemical reactions well known to those skilled in the art. EHSPD can be prepared from 2-ethylhexylthiol and 2,3-epoxy-1-propanediol using chemical reactions well known to those skilled in the art.

[0050] Suitable fatty acid monoester antimicrobial agents include, for example, fatty acid monoesters comprising an aliphatic fatty acid moiety having 6 to 14 carbon atoms and an aliphatic hydroxyl moiety. The term "aliphatic" refers to a straight-chain or branched-chain, saturated or unsaturated hydrocarbon having 6 to 14 carbon atoms. In one embodiment, the aliphatic fatty acid moiety is a straight-chain, saturated or unsaturated hydrocarbon having 8 to 10 carbon atoms. In another embodiment, the aliphatic fatty acid moiety is a branched-chain, saturated or unsaturated hydrocarbon having 8 to 10 carbon atoms.

[0051] The aliphatic hydroxyl moiety of the fatty acid monoester can be any aliphatic compound having at least one hydroxyl group. The aliphatic hydroxyl moiety can have 3 to 9 carbon atoms. The aliphatic hydroxyl moiety can include, but is not limited to, propylene glycol, glycerol, polyalkylene glycols (e.g., polyethylene glycol or polypropylene glycol), cyclic polyols (e.g., sorbitan, glucose, mannose, sucrose, fructose, fucose, inisitol, and derivatives thereof), linear polyols (e.g., mannitol, sorbitol, and derivatives thereof), and mixtures thereof.

[0052] Suitable amidoamine antimicrobial agents include, for example, amidoamines represented by the general formula: [ka] In the formula, R 15 is C6-C 30 is a saturated or unsaturated hydrocarbon, for example, a straight or branched chain, substituted or unsubstituted alkyl, alkylaryl, or alkoxyaryl, m is 0 to 16, n is 2 to 16, and X is -C(O)-NR 16 -or-R 16 NC(O)- and Y is -N(R 17 )2, where R 16 and R 17 Each of is independently hydrogen, C1-C8 saturated or unsaturated alkyl or hydroxyalkyl, or a pharmaceutically acceptable salt thereof.

[0053] As those skilled in the art will readily appreciate, some of the amidoamines used in the contact lens treatment solutions disclosed herein are commercially available. For example, myristamidopropyl dimethylamine is commercially available from Alcon Inc. (Fort Worth, Texas) under the trade name Aldox®. Lauramidopropyl dimethylamine is commercially available from Inolex Chemical Company (Philadelphia, Pennsylvania) under the trade name LEXAMINE® L-13. Stearamidopropyl dimethylamine is also commercially available from Inolex Chemical Company under the trade name LEXAMINE® S-13. The above amidoamines can be synthesized according to known techniques, including those described in U.S. Pat. No. 5,573,726, the contents of which are incorporated herein by reference.

[0054] In exemplary embodiments, the one or more antimicrobial agents described above may be used in an amount that at least partially reduces the number of microorganisms in the used contact lens treatment solution. If desired, the one or more antimicrobial agents may be used in a disinfecting amount that can, for example, reduce the microbial load by at least two log orders in four hours, or one log order in one hour. In one non-limiting exemplary embodiment, a disinfecting amount is an amount that eliminates the microbial load on a contact lens when used as prescribed for the recommended soaking time (FDA Chemical Disinfection Efficacy Test—July, 1985 Contact Lens Solution Draft Guidelines).

[0055] In a non-limiting exemplary embodiment, the antimicrobial / disinfecting agent may be present in the contact lens treatment solution in an amount of about 0.00005 to about 0.15 wt.%, based on the total weight of the contact lens treatment solution. In another exemplary embodiment, the antimicrobial / disinfecting agent may be present in the contact lens treatment solution in an amount of about 0.0001 to about 0.001 wt.%, based on the total weight of the contact lens treatment solution.

[0056] In one or more additional non-limiting exemplary embodiments that can be combined with one or more of the preceding paragraphs, the contact lens treatment solutions disclosed herein may further comprise one or more surfactants. Surfactants suitable for use in contact lens treatment solutions include one or more poloxamers, poloxamines, and mixtures thereof. Representative examples of suitable poloxamers are poloxamer block copolymers. One specific class of poloxamer block copolymers is available under the trademark Pluronic (BASF Wyandotte Corp., Wyandotte, Michigan). Poloxamers include Pluronic® and reverse Pluronic®. Pluronic® is a series of ABA block copolymers composed of blocks of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), as generally represented by Formula I: [ka] wherein a is independently at least 1 and b is at least 1.

[0057] Reverse Pluronic® is a series of BAB block copolymers, each composed of a block of poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide), as generally represented by Formula II: [ka] wherein a is at least 1 and b is independently at least 1. The poly(ethylene oxide) (PEO) blocks are hydrophilic, while the poly(propylene oxide) (PPO) blocks are essentially hydrophobic. Each series of poloxamers has a different ratio of PEO to PPO, which ultimately determines the hydrophilic-lipophilic balance (HLB) of the material. That is, the HLB value varies depending on the values ​​of a and b, where a represents the number of hydrophilic poly(ethylene oxide) units (PEO) present in the molecule and b represents the number of hydrophobic poly(propylene oxide) units (PPO) present in the molecule. In one embodiment, the poloxamer has an HLB of about 5 to about 24. In another embodiment, the poloxamer has an HLB of about 1 to about 5.

[0058] Poloxamers and reverse poloxamers have terminal hydroxyl groups that can be end-functionalized. An example of an end-functionalized poloxamer discussed herein is poloxamer dimethacrylate (e.g., Pluronic® F127 dimethacrylate) disclosed in U.S. Patent Application Publication No. 2003 / 0044468 and U.S. Patent No. 9,309,357, the contents of which are incorporated herein by reference. Another example is the glycidyl-terminated copolymer of polyethylene glycol and polypropylene glycol disclosed in U.S. Patent No. 6,517,933, the contents of which are incorporated herein by reference.

[0059] Poloxamers are functionalized to provide the desired reactivity at the molecular ends. The functionality can vary and is determined depending on the intended use of the functionalized PEO- and PPO-containing block copolymers. That is, the PEO- and PPO-containing block copolymers react with the desired device-forming monomer mixture to provide complementary terminal functionality. As used herein, the term "block copolymer" should be understood to mean a poloxamer having two or more blocks in the polymer backbone.

[0060] In an exemplary embodiment, the one or more poloxamers are present in the contact lens treatment solution in an amount of about 0.001 to about 5.0 wt.%, based on the total weight of the contact lens treatment solution. In another exemplary embodiment, the one or more poloxamers are present in the contact lens treatment solution in an amount of about 0.005 to about 1.0 wt.%, based on the total weight of the contact lens treatment solution.

[0061] Poloxamers and reverse poloxamers are considered to be bifunctional molecules (based on terminal hydroxyl groups), whereas poloxamines are tetrafunctional molecules. That is, these molecules are tetrafunctional block copolymers end-capped with primary hydroxyl groups and linked through a central diamine. One specific class of poloxamine block copolymers is available under the trademark Tetronic (BASF). Poloxamines include Tetronics and reverse Tetronics. Poloxamines have the following general structure, represented by Formula III: [ka] wherein a is independently at least 1 and b is independently at least 1.

[0062] Poloxamines can be functionalized to provide the desired reactivity at the molecular ends. The functionality can vary and is determined depending on the intended use of the functionalized PEO- and PPO-containing block copolymers. That is, the PEO- and PPO-containing block copolymers react with the desired device-forming monomer mixture to provide complementary terminal functionality. As used herein, the term "block copolymer" should be understood to mean a poloxamine having two or more blocks in the polymer backbone(s).

[0063] In an exemplary embodiment, the one or more poloxamines are present in the contact lens treatment solution in an amount of about 0.001 to about 5.0 wt.%, based on the total weight of the contact lens treatment solution. In another exemplary embodiment, the one or more poloxamines are present in the contact lens treatment solution in an amount of about 0.1 to about 1.2 wt.%, based on the total weight of the contact lens treatment solution.

[0064] In one or more additional non-limiting exemplary embodiments that can be combined with one or more of the preceding paragraphs, the contact lens treatment solution disclosed herein may further comprise one or more polysaccharides. In one embodiment, the polysaccharide comprises an anionic polysaccharide. Suitable anionic polysaccharides include, for example, hyaluronic acid or its salts (e.g., sodium hyaluronate or potassium hyaluronate), chondroitin sulfate, chitosan, aloe vera, and carboxymethylcellulose. In one embodiment, the polysaccharide comprises a nonionic polysaccharide. Suitable nonionic polysaccharides include, for example, hemicellulose, hydroxypropylmethylcellulose, methylcellulose, and ethylcellulose.

[0065] In exemplary embodiments, the one or more polysaccharides are present in the contact lens treatment solution in an amount of about 0.01 to about 0.02 wt.%, based on the total weight of the contact lens treatment solution.

[0066] In one or more additional non-limiting exemplary embodiments that can be combined with one or more of the preceding paragraphs, the contact lens treatment solution disclosed herein may further comprise one or more comfort agents. Suitable comfort agents include, for example, polyols, antioxidants, and complex carbohydrates. Suitable polyols include, for example, glucose, mannitol, erythritol, sorbitol, polyvinyl alcohol, maltose, glycerol, and trehalose. Suitable antioxidants include, for example, α-tocopherol and other water-soluble vitamin E moieties, ascorbic acid, ascorbyl glucoside, cysteine, carnosol, carnitine, epicatechin, gallic acid, resveratrol, ellagic acid, pycnogenol, lycopene, astaxanthin, coenzyme Q10, caffeic acid, hydroquinone monomethyl ether, and butylated hydroxytoluene. Suitable complex carbohydrates include, for example, tremella fuciformis polysaccharide and carboxymethylcellulose.

[0067] In an exemplary embodiment, the one or more comfort agents are present in the contact lens treatment solution in an amount of about 0.1 to about 2.0 wt.%, based on the total weight of the contact lens treatment solution. In another exemplary embodiment, the one or more comfort agents are present in the contact lens treatment solution in an amount of about 0.2 to about 1.5 wt.%, based on the total weight of the contact lens treatment solution.

[0068] The contact lens treatment solutions disclosed herein may further include one or more other components commonly found in contact lens treatment solutions. In exemplary embodiments, the contact lens treatment solutions may further include, for example, chelating agents, tonicity modifiers, pH adjusters, viscosity modifiers, demulcents, etc., which serve to increase the comfort of the contact lens treatment solution to the user and / or improve its effectiveness for its intended use.

[0069] In exemplary embodiments, the use of one or more suitable chelating components can assist in removing lipid and protein deposits from the lens surface after daily use.Typically, contact lens treatment solutions contain relatively small amounts, e.g., about 0.005% to about 0.20% (w / v), of ethylenediaminetetraacetic acid (EDTA) or its corresponding metal salt, e.g., the disodium salt (NaEDTA).

[0070] In exemplary embodiments, suitable tonicity adjusters include, for example, dextrose, calcium chloride, magnesium chloride, and the like, and mixtures thereof. These tonicity adjusters are typically used individually in amounts of about 0.01 to about 2.5% w / v. In exemplary embodiments, the tonicity adjuster is used in an amount of about 0.2 to about 1.5% w / v. The tonicity adjuster may be used in an amount that provides a final effective osmolality of at least about 150 mOsm / kg. In one embodiment, the tonicity adjuster is used in an amount that provides a final effective osmolality of about 150 to about 420 mOsm / kg. In exemplary embodiments, the tonicity adjuster is used in an amount that provides a final effective osmolality of about 150 to about 350 mOsm / kg. In exemplary embodiments, the tonicity adjuster is used in an amount that provides a final effective osmolality of about 160 to about 320 mOsm / kg.

[0071] In non-limiting exemplary embodiments, the contact lens treatment solutions disclosed herein can be formulated for instillation directly into the eye, including, for example, eye drops and rewetting drops for rewetting contact lenses during wear, as well as those that also function as multi-purpose solutions. In one non-limiting exemplary embodiment, the contact lens treatment solutions disclosed herein can be formulated as compositions for instillation indirectly into the eye, such as contact lens treatment solutions for treating contact lenses prior to wear on the eye, or packaging solutions for storing lenses.

[0072] The contact lens treatment solutions of exemplary embodiments are physiologically compatible. Specifically, the contact lens treatment solutions should be "ophthalmically safe" when used on contact lenses, meaning that contact lenses treated with the contact lens treatment solution are generally suitable and safe for direct eye wear without rinsing. That is, the contact lens treatment solution is safe and comfortable for routine contact with the eye via a contact lens moistened with the solution. Ophthalmically safe compositions have a tonicity and pH that are compatible with the eye and contain materials and amounts that are non-cytotoxic in accordance with ISO (International Organization for Standardization) standards and U.S. Food and Drug Administration (FDA) regulations. The compositions should be sterile, in that the absence of microbial contaminants in the product must be statistically proven to the extent necessary for such products before the product is released.

[0073] In exemplary embodiments, the pH of the contact lens treatment solutions disclosed herein may be maintained within the range of about 4.0 to about 9.0, about 5.0 to about 8.0, about 6.0 to about 8.0, or about 6.5 to about 7.8. In one exemplary embodiment, the pH of the contact lens treatment solutions disclosed herein may be about 7 or greater.

[0074] In exemplary embodiments, the osmolality of the contact lens treatment solutions disclosed herein may range from about 150 mOsm / kg or at least about 200 mOsmol / kg, up to about 420 mOsmol / kg. In exemplary embodiments, the osmolality of the contact lens treatment solutions disclosed herein may range from about 150 to about 420 mOsm / kg. In another exemplary embodiment, the osmolality of the contact lens treatment solutions disclosed herein may range from about 150 to about 350 mOsm / kg. In another exemplary embodiment, the osmolality of the contact lens treatment solutions disclosed herein may range from about 160 to about 320 mOsm / kg. In one exemplary embodiment, the osmolality of the contact lens treatment solutions disclosed herein may range from about 300 to about 400 mOsm / kg. In another exemplary embodiment, the osmolality of the contact lens treatment solution disclosed herein may be about 350 to about 400 mOsm / kg. The contact lens treatment solution is substantially isotonic or hypertonic (e.g., slightly hypertonic) and ophthalmically acceptable.

[0075] The contact lens treatment solutions disclosed herein may be in the form of droplets and are useful as components of contact lens cleaning, disinfecting, or conditioning compositions containing such materials. In a non-limiting exemplary embodiment, the contact lens treatment solutions disclosed herein can be formulated as a "multi-purpose solution." Multi-purpose solutions are useful for cleaning, disinfecting, storing, and rinsing lenses, particularly soft contact lenses. The use of a multi-purpose solution does not preclude the possibility that some wearers, such as those particularly sensitive to chemical disinfectants or other chemical agents, may prefer to rinse or wet their contact lenses with a separate solution, such as sterile saline, before wearing the lenses. The term "multi-purpose solution" also does not preclude the possibility of periodic cleaning agents that are not used daily, or supplemental cleaning agents for further protein removal, such as enzymatic cleaners typically used weekly. The term "cleaning" means that the solution contains one or more agents in a concentration sufficient to loosen and remove loosely adhering lens deposits and other contaminants from the surface of the contact lens, and may be used in combination with digital manipulation (e.g., manually rubbing the lens with the solution) or with an auxiliary device that agitates the solution in contact with the lens (e.g., a mechanical cleaning aid).

[0076] Conventionally, commercially available multi-purpose solutions require a regimen involving mechanical scrubbing of lenses with the multi-purpose solution to provide the necessary disinfection and cleaning. Such regimens are required by government regulatory agencies (e.g., the FDA) for chemical disinfection systems that are not recognized as chemical disinfecting solutions. In one embodiment, it is possible to formulate a cleaning and disinfecting solution that can provide improved cleaning and disinfection, while being gentle enough to be used as a wetting agent, such as an eye drop. In one embodiment, the contact lens treating solution disclosed herein is formulated to meet the requirements of a single FDA or ISO procedure for contact lens disinfection products.

[0077] Thus, in non-limiting exemplary embodiments, a method for cleaning and disinfecting contact lenses comprises immersing a contact lens in a contact lens treatment solution disclosed herein for a time sufficient to clean and disinfect the contact lens, suitable times may include at least about 30 seconds, or from about 2 hours to about 12 hours, or from about 2 hours to about 4 hours.

[0078] Alternatively, the rubbing protocol may include, in addition to each of the above steps, placing a few drops of contact lens treatment solution on each side of the lens and gently rubbing the surface between the fingers for about 3 to about 10 seconds. The lens may then be rinsed, if necessary, and allowed to soak in the contact lens treatment solution for a suitable period of time, e.g., several minutes or several hours, such as at least two hours. The lens is then removed from the lens storage case and reinserted into the eye.

[0079] The type of contact lens that comes into contact with the contact lens treatment solution disclosed herein is not critical, and any contact lens is contemplated. Representative examples of such lenses include, but are not limited to, soft contact lenses (e.g., soft hydrogel lenses, soft non-hydrogel lenses, etc.), hard contact lenses (e.g., hard gas-permeable lens materials, etc.), rigid gas-permeable (RGP) lenses, intraocular lenses, overlay lenses, etc. As will be understood by those skilled in the art, a lens is considered "soft" if it can be folded without breaking. Any known material for manufacturing contact lenses can be used herein. For example, the preservative-free contact lens treatment solution can be used with (1) hard lenses formed from materials prepared by polymerization of acrylic esters, such as poly(methyl methacrylate) (PMMA), (2) RGP lenses formed from silicone acrylates and fluorosilicone methacrylates, and (3) soft hydrogel contact lenses made from hydrogel polymer materials, such as silicone hydrogels. Hydrogels are defined as crosslinked polymeric systems containing water in equilibrium.

[0080] Hydrogels generally exhibit excellent biocompatibility, i.e., they are biologically or biochemically compatible by not causing toxicity, harmfulness, or immunological reactions in living tissues. Typical conventional hydrogel contact lens materials are manufactured by polymerizing a monomer mixture containing at least one hydrophilic monomer, such as (meth)acrylic acid, 2-hydroxyethyl methacrylate (HEMA), glyceryl methacrylate, N,N-dimethacrylamide, and N-vinylpyrrolidone (NVP). In the case of silicone hydrogels, the monomer mixture used to prepare the copolymer further contains a silicone-containing monomer in addition to the hydrophilic monomer. Typically, the monomer mixture also contains a crosslinking monomer, such as ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, and methacryloxyethyl vinyl carbonate. Alternatively, the silicone-containing monomer or the hydrophilic monomer may function as a crosslinker.

[0081] The following examples are provided to enable one skilled in the art to practice the present invention and are for illustrative purposes only. These examples should not be construed as limiting the scope of the exemplary embodiments defined in the claims. The following abbreviations are used in the examples:

[0082] TRIS: tromethamine buffer.

[0083] Na2EDTA: Ethylenediaminetetraacetic acid disodium salt.

[0084] PAPB: Polyaminopropyl biguanide.

[0085] Polyquaternium-1: A polyquaternium polymer represented by the following structure: [ka]

[0086] Example 1 and Comparative Example A A contact lens treatment solution was prepared by mixing the components listed in Table 1 below in the amounts by weight. [Table 1]

[0087] Example 2 and Comparative Example B A contact lens treatment solution was prepared by mixing the components listed in Table 2 below in the amounts by weight. [Table 2]

[0088] test

[0089] The contact lens treatment solutions of Examples 1 and 2, Comparative Examples A and B were tested for their independent disinfection efficacy. The "single procedure for disinfecting products" was based on the Product Disinfection Efficacy Test established by the U.S. Food and Drug Administration, Division of Ophthalmic Devices, May 1, 1997, and ISO 14729. In the independent test, disinfection products were challenged with a standard inoculum of a representative range of microorganisms, and the degree of reduction in viability was determined over a predetermined period equivalent to the period during which the product was likely to be used. The primary criterion for the predetermined disinfection period (corresponding to the minimum recommended disinfection period) was that the number of bacteria recovered per milliliter (mL) must have an average reduction of at least 3.0 logs within the predetermined disinfection period. The number of molds and yeasts recovered per mL must have an average reduction of at least 1.0 logs within the minimum recommended disinfection time, with no increase observed after four times the minimum recommended disinfection time. The antimicrobial efficacy of each of the various compositions was evaluated in the presence of organic soil.

[0090] The single bactericidal test was carried out as follows.

[0091] Microbial challenge inocula were prepared using Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 9027), Serratia marcescens (ATCC 13880), Candida albicans (ATCC 10231), and Fusarium solani (ATCC 36031). The challenge organisms were transferred to the recommended agar medium and incubated for the appropriate time and temperature. Cultures were harvested using sterile Dulbecco's phosphate-buffered saline (DPBST) supplemented with 0.05% w / v polysorbate 80 or an appropriate dilution and transferred to appropriate containers. Spore suspensions were filtered through sterile glass wool to remove mycelial debris. Serratia marcescens was filtered through a 1.2 μm filter, if necessary, to clarify the suspension. After collection, the suspension was centrifuged at 5000 x g for up to 30 minutes at 20-25°C. The supernatant was decanted and diluted to 1 x 10 in DPBST or other appropriate diluent. 7 ~1×10 8 The cells were resuspended to a concentration of cfu / ml.

[0092] The appropriate microbial concentration was estimated by measuring the turbidity of the suspension at a preselected wavelength (e.g., 490 nm) using, for example, a spectrophotometer. One test tube containing a minimum of 10 mL of test solution was prepared per challenge microorganism. Inoculum controls (IC) were prepared by dispersing an identical aliquot of inoculum in the appropriate diluent (DPBST) using the same volume as the test sample. At the start of the test (T=0), the IC of each challenge microorganism was serially diluted and plated on the appropriate agar medium. Each test tube of solution to be tested contained a final count of 1 x 10 5 ~1×10 6The samples were inoculated with a suspension of the test microorganism sufficient to produce cfu / mL, with the inoculum volume not exceeding 1% of the sample volume. Dispersion of the inoculum was ensured by thoroughly mixing the samples (e.g., vortexing each tube for a minimum of 5 seconds). The inoculated products were stored at 20-25°C. 1.0 mL aliquots of the inoculated products were taken to measure viable counts after a period of disinfection.

[0093] The suspension was thoroughly mixed by vortexing vigorously for at least 5 seconds. 1.0 mL aliquots taken at designated time intervals were subjected to appropriate 10-fold serial dilutions in active neutralization medium. The suspension was vigorously mixed and incubated for the appropriate time (a minimum of 10 minutes and no more than 1 hour before plating) to allow for neutralization of the microbial agent. Viable counts were determined at the appropriate dilutions by preparing duplicate plates of trypticase soy agar (TSA) for bacteria and Sabouraud dextrose agar (SDA) for molds and yeasts. Bacterial recovery plates were incubated at 30°C–35°C for 2–4 days. Yeast recovery plates were incubated at 20°C–25°C or 30°C–35°C for 3–5 days. Mold recovery plates were incubated at 20°C–25°C for 4–7 days. The average number of colony-forming units (cfu) was determined on the countable plates. A countable plate is defined as 30-300 cfu / plate for bacteria and yeast, and 8-80 cfu / plate for mold (10 colonies). 0 or 10 -1 (Except when the reduction was observed only on the dilution plate of 10 ... 5 ~1.0x10 6 It should be cfu / mL.

[0094] The log reduction values ​​of the contact lens treatment solutions of Examples 1 and 2, Comparative Examples A and B in the 4-hour disinfection efficacy test are shown in Table 3 below. [Table 3]

[0095] The contact lens treatment solutions of Examples 1 and 2 each had significantly improved disinfecting effects against Candida albicans species compared to the contact lens treatment solutions of Comparative Examples A and B.

[0096] Example 3 and Comparative Example C A contact lens treatment solution was prepared by mixing the components listed in Table 4 below in the amounts by weight. [Table 4]

[0097] Example 4 and Comparative Example D A contact lens treatment solution was prepared by mixing the components listed in Table 5 below in the amounts by weight. [Table 5]

[0098] Comparative Examples E to H A contact lens treatment solution was prepared by mixing the components listed in Table 6 below in the amounts by weight. [Table 6]

[0099] test

[0100] The contact lens treatment solutions of Example 3, Example 4, and Comparative Examples C-H were tested using the Disinfection Effectiveness Test as described above. The log reduction values ​​for the 4-hour Disinfection Effectiveness Test are shown in Table 7 below. [Table 7]

[0101] The contact lens treatment solutions of Examples 3 and 4 each exhibited significantly improved disinfecting efficacy against Candida albicans compared to the contact lens treatment solutions of Comparative Examples C to H. Comparing the contact lens treatment solutions of Examples 3 and 4 with the contact lens treatment solutions of Comparative Examples C and D, it can be seen that the inclusion of potassium chloride in the alexidine-containing contact lens treatment solutions of Examples 3 and 4 significantly improved disinfecting efficacy against Candida albicans compared to the inclusion of sodium chloride in the alexidine-containing solutions of Comparative Examples C and D. Comparative Examples E and F demonstrate that the inclusion of potassium chloride in a contact lens treatment solution containing only polyquaternium-1, but not alexidine, does not improve disinfecting efficacy against Candida albicans. Comparative Examples G and H also demonstrate that the inclusion of potassium chloride in a contact lens treatment solution containing only PAPB, but not alexidine, does not affect disinfecting efficacy compared to the inclusion of sodium chloride in a contact lens treatment solution containing only PAPB, but not alexidine.

[0102] Example 5 and Comparative Example 1 A contact lens treatment solution was prepared by mixing the components listed in Table 8 below in the amounts by weight. [Table 8]

[0103] test

[0104] The contact lens treatment solutions of Example 5 and Comparative Example I were tested using the Disinfection Effectiveness Test described above. The log reduction values ​​for the 4-hour Disinfection Effectiveness Test are shown in Table 9 below. [Table 9]

[0105] The contact lens treatment solution of Example 5 demonstrated significantly improved disinfecting efficacy against Candida albicans species compared to the contact lens treatment solution of Comparative Example 1. Therefore, it can be seen that the addition of potassium chloride to the alexidine-containing contact lens treatment solution of Example 5 significantly improved efficacy compared to the addition of sodium chloride to the alexidine-containing contact lens treatment solution of Comparative Example 1.

[0106] Example 6, Comparative Examples J to L A contact lens treatment solution was prepared by mixing the components listed in Table 10 below in the amounts by weight. [Table 10]

[0107] test

[0108] The contact lens treatment solutions of Example 6 and Comparative Examples J-L were tested using the Disinfection Effectiveness Test described above. The log reduction values ​​for the 4-hour Disinfection Effectiveness Test are shown in Table 11 below. [Table 11]

[0109] When comparing the contact lens treatment solution of Example 6 with the contact lens treatment solution of Comparative Example J, it can be seen that the inclusion of potassium chloride in a contact lens treatment solution containing alexidine significantly improved the disinfecting effect compared to the inclusion of sodium chloride. Comparative Examples K and L demonstrate that the inclusion of potassium chloride in a contact lens treatment solution containing only PAPB but not alexidine does not affect the disinfecting effect compared to the inclusion of sodium chloride in a contact lens treatment solution containing only PAPB but not alexidine.

[0110] Examples 7 to 9, Comparative Examples M to O A contact lens treatment solution was prepared by mixing the components listed in Table 12 below in the amounts by weight. [Table 12]

[0111] test The contact lens treatment solutions of Examples 7-9 and Comparative Examples M-O were tested using the Disinfection Effectiveness Test described above. The log reduction values ​​for the 4-hour Disinfection Effectiveness Test are shown in Table 13 below. [Table 13]

[0112] The contact lens treatment solutions of Examples 7 to 9, each containing alexidine and a potassium salt buffer, show improved disinfection effects against Staphylococcus aureus and Candida albicans compared to the contact lens treatment solutions of Comparative Examples M to O, each containing alexidine and an equivalent amount of a sodium salt buffer.

[0113] Example 11 and Comparative Example S A contact lens treatment solution was prepared by mixing the components listed in Table 14 below in the amounts by weight. [Table 14]

[0114] test

[0115] The contact lens treatment solutions of Example 10 and Comparative Example P were tested using the Disinfection Effectiveness Test described above. The log reduction values ​​for the 4-hour Disinfection Effectiveness Test are shown in Table 15 below. [Table 15]

[0116] The contact lens treatment solution of Example 10 demonstrated significantly improved disinfecting efficacy against Candida albicans species compared to the contact lens treatment solution of Comparative Example P.

[0117] The following exemplary contact lens treatment solutions I-VIII are provided in accordance with non-limiting exemplary embodiments disclosed herein and can be prepared by mixing the following components in the amounts by weight listed in Table 16. These contact lens treatment solutions have a pH of about 7.7 and an osmolality of about 255 mOsm / kg. [Table 16]

[0118] According to one aspect of the present invention, a contact lens treatment solution comprises: (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate; (b) an antimicrobial agent comprising alexidine or a salt or free base thereof; and (c) optionally, one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate, wherein the one or more potassium salts are present in an amount greater than the amount of the one or more sodium salts, if present.

[0119] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the one or more potassium salts include potassium chloride and the corresponding sodium salt is sodium chloride.

[0120] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the antimicrobial agent includes alexidine.

[0121] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the contact lens treatment solution comprises: (a) from about 0.02 to about 1.5 wt. % of one or more potassium salts, based on the total weight of the contact lens treatment solution; and (b) from about 0.0001 to about 0.0006 wt. % of an antimicrobial agent, based on the total weight of the contact lens treatment solution.

[0122] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the contact lens treatment solution comprises: (a) from about 0.03 to about 0.9 wt. % of one or more potassium salts, based on the total weight of the contact lens treatment solution; and (b) from about 0.0002 to about 0.0003 wt. % of an antimicrobial agent, based on the total weight of the contact lens treatment solution.

[0123] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the contact lens treatment solution further comprises one or more additional antimicrobial agents.

[0124] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the one or more additional antimicrobial agents include one or more polyquaternium polymers.

[0125] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the one or more polyquaternium polymers include from about 30 to about 50,000 quaternary amine functional repeat units.

[0126] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the one or more polyquaternium polymers have a weight average molecular weight Mw of from about 3,000 to about 5,000,000.

[0127] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the one or more polyquaternium polymers have a weight average molecular weight Mw of from about 5,000 to about 40,000.

[0128] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the one or more polyquaternium polymers are cationic.

[0129] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the one or more polyquaternium polymers include polyquaternium-1.

[0130] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the contact lens treatment solution comprises about 0.0001 wt.% to about 0.0003 wt.% of one or more polyquaternium polymers, based on the total weight of the contact lens treatment solution.

[0131] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the one or more additional antimicrobial agents are selected from the group consisting of a polymeric biguanide or a salt or free base thereof, a terpene compound, a branched glycerol monoalkyl ether, a branched glycerol monoalkyl amine, a branched glycerol monoalkyl sulfide, a fatty acid monoester comprising an aliphatic fatty acid moiety and an aliphatic hydroxyl moiety having 6 to 14 carbon atoms, an amidoamine compound, and combinations thereof.

[0132] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the polymeric biguanide, or a salt or free base thereof, is a polymeric hexamethylene biguanide.

[0133] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the contact lens treatment solution further comprises one or more surfactants.

[0134] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the one or more surfactants are selected from the group consisting of poloxamers, poloxamines, and mixtures thereof.

[0135] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the poloxamer is at least one of a poloxamer di(meth)acrylate and a reverse poloxamer di(meth)acrylate, and the poloxamine is at least one of a poloxamine di(meth)acrylate and a reverse poloxamine di(meth)acrylate.

[0136] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the poloxamer is present in the contact lens treatment solution in an amount of about 0.001 to about 5.0 wt.%, based on the total weight of the contact lens treatment solution, and the poloxamine is present in the contact lens treatment solution in an amount of about 0.001 to about 5.0 wt.%, based on the total weight of the contact lens treatment solution.

[0137] In one or more additional exemplary embodiments that may be combined with the preceding paragraph, the contact lens treatment solution further comprises one or more comfort agents.

[0138] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the one or more comfort agents are selected from the group consisting of polyols, antioxidants, and complex carbohydrates.

[0139] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the polyol is one or more of glycerol and erythritol.

[0140] In one or more additional exemplary embodiments that may be combined with the preceding paragraph, the contact lens treating solution further comprises one or more polysaccharides.

[0141] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the one or more polysaccharides include one or more of an anionic polysaccharide and a nonionic polysaccharide.

[0142] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the one or more polysaccharides include one or more of hyaluronic acid or a salt thereof, chondroitin sulfate, chitosan, aloe vera, carboxymethylcellulose, hemicellulose, hydroxypropylmethylcellulose, methylcellulose, and ethylcellulose.

[0143] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the contact lens treatment solution further comprises one or more of a chelating agent, a tonicity adjusting agent, a buffering agent, a pH adjusting agent, a viscosity adjusting agent, and a demulcent.

[0144] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the sodium salt includes one or more of sodium chloride, sodium citrate, and sodium phosphate.

[0145] In one or more additional exemplary embodiments that can be combined with the preceding paragraph, the contact lens treatment solution is in the form of an eye care product or a contact lens care product selected from the group consisting of eye drops, contact lens storage solution, contact lens cleaning solution, and multi-purpose contact lens solution.

[0146] In one or more additional exemplary embodiments that can be combined with the previous paragraph, the contact lens treatment solution is in the form of a multi-purpose solution or rewetting drops.

[0147] According to another aspect of the present invention, a method of cleaning and disinfecting contact lenses comprises immersing a contact lens in one or more contact lens treatment solutions according to one or more of the exemplary embodiments that can be combined with the preceding paragraph for a time sufficient to clean and disinfect the contact lens, said treatment solutions comprising: (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate; (b) an antimicrobial agent comprising alexidine or a salt or free base thereof; and (c) optionally, one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate.

[0148] According to yet another aspect of the present invention, a method for inhibiting bacterial adhesion to a surface of a contact lens comprises contacting the surface of a contact lens with one or more contact lens treatment solutions according to one or more exemplary embodiments that can be combined with the preceding paragraph, the contact lens treatment solution comprising: (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate; (b) an antimicrobial agent comprising alexidine or a salt or free base thereof; and (c) optionally, one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate.

[0149] Although compositions and methods are described in terms of "comprising" various components or steps, unless otherwise specified, the compositions and methods can also "consist essentially of" or "consist of" the various components or steps.

[0150] The terms "a," "an," and "the" are intended to include plural alternatives, e.g., at least one. The terms "including," "with," and "having," as used herein, are defined as "comprising" (i.e., open-ended) unless otherwise specified.

[0151] Various numerical ranges are disclosed herein. When an applicant discloses or claims a range, the applicant's intention is to separately disclose or claim each possible numerical value that the range may reasonably encompass, the endpoints of the range, and any subranges and combinations of subranges contained therein, unless otherwise specified. For example, all endpoints of ranges disclosed herein are approximations unless excluded by disclaimer.

[0152] Values ​​or ranges may be expressed herein as "about," "from one particular value modified by about," and / or to another particular value modified by about." When such values ​​or ranges are expressed, other disclosed embodiments include the stated particular value, from the one particular value, and / or to the other particular value. Similarly, when values ​​are expressed as approximations, by use of the antecedent "about," it is understood that the particular value forms another embodiment. Furthermore, when more than one value is disclosed herein, it is understood that each value is also disclosed herein as "about" that particular value in addition to the value itself. In other aspects, use of the term "about" means ±20% of the stated value, ±15% of the stated value, ±10% of the stated value, ±5% of the stated value, ±3% of the stated value, or ±1% of the stated value.

[0153] Applicant reserves the right to conditionally exclude individual members of groups of values ​​or ranges (including subranges or combinations of subranges within groups) that could be claimed according to ranges or in a similar manner if, for any reason, applicant chooses to claim less than the full scope of the disclosure, for example, to account for references that applicant was not aware of at the time of filing. Additionally, applicant reserves the right to exclude or exclude members of any group that it has claimed.

[0154] Various features of the compositions are described for brevity in the context of a single embodiment, but may also be provided separately or in any suitable subcombination. All combinations of embodiments are specifically embraced in the exemplary embodiments disclosed herein, just as if each and every combination were individually and explicitly disclosed. Furthermore, all subcombinations listed in the embodiments describing such variations are also specifically embraced in the compositions of the present invention, and are disclosed herein just as if each and every such subcombination were individually and explicitly disclosed herein.

[0155] It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore, the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. For example, the functions described and implemented above as the best mode for carrying out the invention are for illustrative purposes only. Those skilled in the art may implement other configurations and methods without departing from the scope and spirit of the invention. Moreover, those skilled in the art will envision other modifications without departing from the scope and spirit of the features and advantages attendant thereto.

Claims

1. (a) one or more potassium salts selected from the group consisting of potassium chloride, potassium citrate, potassium hydroxide, potassium borate, potassium ethylenediaminetetraacetate, and potassium phosphate; (b) an antibacterial agent comprising alexidine or a salt or free base thereof; (c) optionally one or more sodium salts selected from the group consisting of sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium ethylenediaminetetraacetate, and sodium borate; A contact lens treating solution wherein said one or more potassium salts, if present, are present in an amount greater than said one or more sodium salts.

2. 10. The contact lens treatment solution of claim 1, wherein the one or more potassium salts include potassium chloride and the corresponding sodium salt is sodium chloride.

3. The contact lens treatment solution of claim 1 or 2, wherein the antibacterial agent comprises alexidine.

4. (a) about 0.02 to about 1.5 wt. % of said one or more potassium salts, based on the total weight of said contact lens treatment solution; 4. The contact lens treatment solution according to claim 1, further comprising: (b) about 0.0001 to about 0.0006 wt. % of said antimicrobial agent, based on the total weight of said contact lens treatment solution.

5. (a) about 0.03 to about 0.9 wt. % of said one or more potassium salts, based on the total weight of said contact lens treatment solution; 4. The contact lens treatment solution according to claim 1, further comprising: (b) about 0.0002 to about 0.0003 wt. % of said antimicrobial agent, based on the total weight of said contact lens treatment solution.

6. The contact lens treatment solution of any one of claims 1 to 5, further comprising one or more additional antimicrobial agents.

7. The contact lens treatment solution of claim 6 , wherein the one or more additional antimicrobial agents comprise one or more polyquaternium polymers.

8. 8. The contact lens treatment solution of claim 7, wherein the one or more polyquaternium polymers contain from about 30 to about 50,000 quaternary amine functional repeating units.

9. 8. The contact lens treatment solution of claim 7, wherein the one or more polyquaternium polymers have a weight average molecular weight Mw of from about 3,000 to about 5,000,000.

10. 8. The contact lens treatment solution of claim 7, wherein the one or more polyquaternium polymers have a weight average molecular weight Mw of from about 5,000 to about 40,000.

11. 8. The contact lens treatment solution of claim 7, wherein the one or more polyquaternium polymers are cationic.

12. 8. The contact lens treatment solution of claim 7, wherein the one or more polyquaternium polymers comprise polyquaternium-1.

13. 13. The contact lens treatment solution of any one of claims 7 to 12, comprising from about 0.0001 wt. % to about 0.0003 wt. % of said one or more polyquaternium polymers, based on the total weight of said contact lens treatment solution.

14. 7. The contact lens treatment solution of claim 6, wherein the one or more additional antimicrobial agents are selected from the group consisting of polymeric biguanides or salts or free bases thereof, terpene compounds, branched glycerol monoalkyl ethers, branched glycerol monoalkyl amines, branched glycerol monoalkyl sulfides, fatty acid monoesters comprising an aliphatic fatty acid moiety and an aliphatic hydroxyl moiety having 6 to 14 carbon atoms, an amidoamine compound, and combinations thereof.

15. 15. The contact lens treatment solution of claim 14, wherein the polymeric biguanide, or salt or free base thereof, is a polymeric hexamethylene biguanide.

16. The contact lens treatment solution of any one of claims 1 to 15, further comprising one or more surfactants.

17. 17. The contact lens treatment solution of claim 16, wherein the one or more surfactants are selected from the group consisting of poloxamers, poloxamines, and mixtures thereof.

18. 18. The contact lens treatment solution of claim 17, wherein the poloxamer is present in the contact lens treatment solution in an amount of about 0.001 to about 5.0 wt.%, based on the total weight of the contact lens treatment solution, and the poloxamine is present in the contact lens treatment solution in an amount of about 0.001 to about 5.0 wt.%, based on the total weight of the contact lens treatment solution.

19. The contact lens treatment solution of any one of claims 1 to 18, further comprising one or more comfort agents.

20. 20. The contact lens treatment solution of claim 19, wherein the one or more comfort agents are selected from the group consisting of polyols, antioxidants, and complex carbohydrates.

21. 21. The contact lens treatment solution of claim 20, wherein the polyol is one or more of glycerol and erythritol.

22. The contact lens treatment solution of any one of claims 1 to 21, further comprising one or more polysaccharides.

23. 23. The contact lens treating solution of claim 22, wherein the one or more polysaccharides comprise one or more of anionic polysaccharides and nonionic polysaccharides.

24. 23. The contact lens treatment solution of claim 22, wherein the one or more polysaccharides comprise one or more of hyaluronic acid or a salt thereof, chondroitin sulfate, chitosan, aloe vera, carboxymethylcellulose, hemicellulose, hydroxypropylmethylcellulose, methylcellulose, and ethylcellulose.

25. 25. The contact lens treatment solution of any one of claims 1 to 24, further comprising one or more of a chelating agent, a tonicity adjusting agent, a buffering agent, a pH adjusting agent, a viscosity adjusting agent, and a demulcent.

26. 26. The contact lens treatment solution of any one of claims 1 to 25, wherein the sodium salt comprises one or more of sodium chloride, sodium citrate, and sodium phosphate.

27. 27. The contact lens treatment solution of any one of claims 1 to 26, in the form of an eye care product or contact lens care product selected from the group consisting of eye drops, contact lens storage solution, contact lens cleaning solution, and multipurpose contact lens solution.

28. A contact lens treatment solution according to any one of claims 1 to 26 in the form of a multipurpose solution or rewetting drops.

29. 29. A method of cleaning and disinfecting a contact lens, comprising immersing the contact lens in one or more contact lens treatment solutions according to any one of claims 1 to 28 for a time sufficient to clean and disinfect the contact lens.

30. 29. A method of inhibiting bacterial adhesion to a surface of a contact lens, the method comprising contacting the surface of the contact lens with one or more of the contact lens treatment solutions of any one of claims 1 to 28.

31. Use of a contact lens treatment solution according to any one of claims 1 to 28 for cleaning and disinfecting contact lenses.

32. Use of the contact lens treatment solution according to any one of claims 1 to 28 for inhibiting bacterial adhesion to the surface of a contact lens.

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