Contact lens treatment solution

Abstract

The contact lens treatment solution comprises (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, and (b) one or more antimicrobial agents containing one or more polyquaternium polymers.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 419,468, filed on 26 October 2022, titled "Contact Lens Treating Solution." The contents of this document are incorporated herein by reference in their entirety. [Background technology]

[0002] Contact lenses are increasingly being used as a means of correcting vision and / or compensating for eye abnormalities. However, since contact lenses are typically worn and removed daily, and must be cleaned and disinfected after each use, sterile solutions and containers are required.

[0003] During contact lens insertion and normal handling, microorganisms and biomolecules (such as lipids and proteins) can adhere to the contact lenses and contaminate the solution and / or storage container. Furthermore, the tear film, which may contain proteins, lipids, and even microorganisms, can cover the surface of the eye. Any of these components found in the tear film, on the outer surface of the eyeball, or on the surrounding skin can be carried into the contact lens solution and / or storage container. Moreover, microorganisms that grow in the solution and / or storage container can travel to the eyeball via the contact lens and become pathogens that can cause eye infections resulting in visual impairment and blindness. Various solutions have been developed to clean these deposits and disinfect microorganisms. [Overview of the Initiative]

[0004] According to an exemplary embodiment, the contact lens treatment solution comprises (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers.

[0005] The contact lens treatment solution of the exemplary embodiment advantageously exhibits significantly improved disinfection efficacy against both bacterial and fungal species after autoclaving. In addition, the contact lens treatment solution of the exemplary embodiment is an improved contact lens treatment solution in which the polyquaternium polymer (e.g., polyquaternium-1) maintains its disinfection and preservative effects even when exposed to high temperatures.

[0006] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains tris(hydroxymethyl)aminomethane or a salt thereof as component (a).

[0007] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane as component (a).

[0008] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, in an amount of about 0.05 to about 2.0 wt.% based on the total weight of the contact lens treatment solution, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers, in an amount of about 0.00001 to about 0.0010 wt.% based on the total weight of the contact lens treatment solution.

[0009] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane, and salts thereof, in an amount of about 0.1 to about 1.0 wt.% based on the total weight of the contact lens treatment solution, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers, in an amount of about 0.00002 to about 0.0003 wt.% based on the total weight of the contact lens treatment solution.

[0010] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, one or more polyquaternium polymers contain about 30 to about 50,000 quaternary amine functional repeating units.

[0011] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, one or more polyquaternium polymers have a weight-average molecular weight Mw of about 3,000 to about 5,000,000.

[0012] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, one or more polyquaternium polymers have a weight-average molecular weight Mw of about 5,000 to about 40,000.

[0013] In one or more further exemplary embodiments, one or more polyquaternium polymers are cationic, as can be combined with the preceding paragraph.

[0014] In one or more further exemplary embodiments, the polyquaternium polymer comprises polyquaternium-1, as can be combined with the preceding paragraph.

[0015] In one or more further exemplary embodiments, the contact lens treatment solution further comprises one or more surfactants, as may be combined with the preceding paragraph.

[0016] In one or more further exemplary embodiments, so as to be combinable with the previous paragraph, one or more surfactants are selected from the group consisting of poloxamers, poloxamines, and mixtures thereof.

[0017] In one or more further exemplary embodiments, so as to be combinable with the previous paragraph, the poloxamer is at least one of poloxamer di(meth)acrylate and reverse poloxamer di(meth)acrylate, and the poloxamine is at least one of poloxamine di(meth)acrylate and reverse poloxamine di(meth)acrylate.

[0018] In one or more further exemplary embodiments, so as to be combinable with the previous paragraph, the poloxamer is present in the contact lens treatment solution in an amount ranging from 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 ranging from about 0.001 to about 5.0 wt.% based on the total weight of the contact lens treatment solution.

[0019] In one or more further exemplary embodiments, so as to be combinable with the previous paragraph, the contact lens treatment solution further comprises one or more additional antibacterial agents.

[0020] In one or more further exemplary embodiments, so as to be combinable with the previous paragraph, one or more additional antibacterial agents are selected from the group consisting of polymeric biguanide or its salt or free base, terpene compound, branched glycerol monoalkyl ether, branched glycerol monoalkylamine, branched glycerol monoalkyl sulfide, fatty acid monoester (the fatty acid monoester contains an aliphatic fatty acid moiety having 6 to 14 carbon atoms and an aliphatic hydroxyl moiety), amidoamine compound, and combinations thereof.

[0021] In one or more further exemplary embodiments, the contact lens treatment solution further comprises one or more comfort agents, as may be combined with the previous paragraph.

[0022] In one or more further exemplary embodiments, the one or more comfort agents are selected from the group consisting of polyols, antioxidants, and complex carbohydrates, as may be combined with the previous paragraph.

[0023] In one or more further exemplary embodiments, the polyol is one or more of glycerol and erythritol, as may be combined with the previous paragraph.

[0024] In one or more further exemplary embodiments, the contact lens treatment solution further comprises one or more polysaccharides, as may be combined with the previous paragraph.

[0025] In one or more further exemplary embodiments, the one or more polysaccharides include one or more of anionic polysaccharides and nonionic polysaccharides, as may be combined with the previous paragraph.

[0026] In one or more further exemplary embodiments, the one or more polysaccharides include one or more of hyaluronic acid or its salts, chondroitin sulfate, chitosan, aloe vera, carboxymethyl cellulose, hemicellulose, hydroxypropyl methylcellulose, methylcellulose, and ethylcellulose, as may be combined with the previous paragraph.

[0027] In one or more further exemplary embodiments, the contact lens treatment solution further comprises one or more of chelating agents, tonicity adjusting agents, buffering agents, pH adjusting agents, viscosity adjusting agents, and lubricants, as may be combined with the previous paragraph.

[0028] In one or more further exemplary embodiments, the contact lens treatment solution contains a borate buffer in an amount less than 0.3 wt.%.

[0029] In one or more further exemplary embodiments, the contact lens treatment solution does not contain a borate buffer, as may be combined with the preceding paragraph.

[0030] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution is in the form of an eye care or contact lens care product selected from the group consisting of eye drops, contact lens storage solutions, contact lens cleaning solutions, and contact lens multipurpose solutions.

[0031] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution is in the form of a multipurpose solution or a re-wetting eye drop.

[0032] According to another exemplary embodiment, a method for cleaning and disinfecting contact lenses comprises immersing the contact lenses in a contact lens treatment solution for a time sufficient to clean and disinfect the contact lenses, the contact lens treatment solution comprising (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers.

[0033] According to yet another exemplary embodiment, a method for inhibiting bacterial adhesion to the surface of a contact lens includes contacting the surface of the contact lens with a contact lens treatment solution comprising (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers. [Modes for carrying out the invention]

[0034] The exemplary embodiments described herein relate to contact lens treatment solutions for cleaning, rinsing, storing, and / or disinfecting contact lenses. For example, “daily cleaners” containing various types of surfactants and disinfectants are recommended for daily use to remove most deposits and debris from contact lenses. In approaches to prevent protein deposits, contact lens treatment solutions containing chemicals (e.g., cationic polymers) have been developed to prevent proteins from adhering to the contact lens surface of hard oxygen-permeable (RGP) contact lenses and soft contact lenses. In addition, both hard and soft contact lenses often require a solution to moisten the lens before insertion into the eye, although their formulations have tended to differ based on their different properties. After contact lenses have been inserted into the eye, ophthalmic solutions can be applied to the eye by eyedroppers for re-moistening, lubrication, and / or improving the comfort of the contact lens wearer. Hypotonic and isotonic solutions for improving the comfort of wearing soft contact lenses by directly adding them to the contact lens in the eye typically contain viscosity enhancers, lubricants, surfactants, buffers, preservatives, and salts.

[0035] Multipurpose solutions are popular due to their convenience, as they allow for the cleaning, disinfection, and preparation of contact lenses in a single solution immediately before insertion. Multipurpose solutions are also designed to be used as no-rinse wetting agents, meaning the solution must be ophthalmologically safe even if it comes into contact with the eye. Therefore, the types and concentrations of both cleaning agents and biocides that can be used in the solution are somewhat limited, as preservatives or disinfectants tend to irritate the eye. Furthermore, surfactants must not inhibit the wetting or conditioning function of the solution.

[0036] Polyquaternium-1 is a known disinfectant / antimicrobial and preservative used in various lens care solutions. Currently available lens care products utilize polyquaternium-1 in conjunction with borate, borate / citrate, borate / citrate-glycylglycine, and citrate buffer systems. However, exposure of these buffer systems containing polyquaternium-1 to high temperatures can lead to degradation of the polyquaternium-1, potentially reducing their disinfectant and preservative effects.

[0037] Accordingly, the non-limiting exemplary embodiments described herein address the aforementioned problems by providing an improved contact lens treatment solution in which a polyquaternium polymer (e.g., polyquaternium-1) maintains its disinfecting and antiseptic effects even when exposed to high temperatures.

[0038] A contact lens treatment solution according to a non-limiting exemplary embodiment comprises at least (a) one or more of tris(hydroxymethyl)aminomethane (TRIS), bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane (bis-Tris), and salts thereof, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers.

[0039] Tris(hydroxymethyl)aminomethane (2-amino-2-(hydroxymethyl)propane-1,3-diol) or its salts, also known as tromethamine, are commonly referred to as Tris, Tris buffer, or Tris base. In one non-limiting exemplary embodiment, the Tris component is tris(hydroxymethyl)aminomethane in its base form. Bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane or its salts are commonly referred to as bis-Tris.

[0040] In exemplary embodiments, one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane, and their salts are present in the contact lens treatment solution in an amount ranging from about 0.05 to about 2.0 wt.% based on the total weight of the contact lens treatment solution. In other embodiments, one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane, and their salts are present in the contact lens treatment solution in an amount ranging from about 0.1 to about 1.0 wt.% based on the total weight of the contact lens treatment solution.

[0041] The contact lens treatment solution further contains one or more antimicrobial agents comprising one or more polyquaternium polymers, salts thereof, or free bases thereof. In exemplary embodiments, one or more polyquaternium polymers may have quaternary amine-functional repeating units ranging from about 30 to about 50,000 units. In one typical embodiment, at least one polyquaternium polymer may have quaternary amine-functional repeating units ranging from about 50 to about 2,000 units. "Quaternary amine-functional repeating unit" is understood herein to mean a repeating unit comprising a quaternary amine group (a positively charged nitrogen atom covalently bonded to four radicals (without hydrogen atoms) and ionically bonded to a negatively charged counterion (e.g., chloride)).

[0042] One or more polyquaternium polymers can have a weight-average molecular weight Mw of approximately 3,000 to approximately 5,000,000. In one typical embodiment, at least one polyquaternium polymer can have a weight-average molecular weight Mw of approximately 5,000 to approximately 500,000. In one typical embodiment, one or more polyquaternium polymers can have a weight-average molecular weight Mw of approximately 5,000 to approximately 200,000. In one typical embodiment, one or more polyquaternium polymers can have a weight-average molecular weight Mw of approximately 5,000 to approximately 50,000. In one typical embodiment, one or more polyquaternium polymers can have a weight-average molecular weight Mw of approximately 5,000 to approximately 30,000.

[0043] In non-limiting exemplary embodiments, polyquaternium polymers useful herein may include copolymers in which a quaternary amine-functional repeating unit is derived from one or more monomers of the following types: 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, their halides or other salt forms, and their derivatives (including substitution, addition, or removal of alkyl groups, such as alkyl groups having 1 to 6 carbon atoms). Quaternary amine-functional repeating units can also be obtained as reaction products or as two or more compounds by using, for example, strong alkylating agents (e.g., 1,4-dichloro-2-butene, which can be reacted with 1,4-bis[dimethylaminool]-2-butene and triethanolamine to produce polymeric polyquaternary ammonium compounds). Quaternary amine-functional repeating units can also be made from other polymers, for example, by the reaction of trimethylammonium-substituted epoxides with the hydroxyl groups of hydroxyethylcellulose. Suitable quaternary amine-functional repeating units also include those found in polymeric ionenes formed by polycondensation reactions. In such repeating units, the nitrogen of the quaternary amine is integrated with the polymer backbone and located between alkylene, oxyalkylene, or other segments.

[0044] In exemplary embodiments, the nitrogen in the quaternary amine functional repeating unit is part of a saturated or unsaturated heterocycle (e.g., a five-membered or six-membered ring). In one embodiment, the polyquaternium polymer is a copolymer of a vinylimidazolium salt or a dimethyldiallylammonium salt. In one embodiment, up to about 90% (e.g., about 40% to about 90% moles) of copolymerizable comonomers without quaternary amine functional groups may be copolymerized with comonomers with quaternary amine functional groups. Suitable comonomers include, for example, vinylpyrrolidone, acrylic acid, alkyl methacrylates, amides and amines such as acrylamide, and N,N-dialkylaminoalkyl acrylates and methacrylates, hydroxyethylcellulose, and copolymerizable mixtures thereof. In one embodiment, the alkyl group has 1 to 6 carbon atoms.

[0045] Polyquaternium polymers as defined in this manner are a well-known type of polymer, and many variations are commercially available. For example, the current CTFA International Dictionary of Cosmetic Ingredients includes polyquaterniums designated as polyquaternium-1 to polyquaternium-68, some of which are useful in the exemplary embodiments disclosed herein based on this teaching. Polymerization techniques for preparing such materials are also well known to those skilled in the art, and many variations of such techniques are also commercially practiced. New variations of such polyquaternium polymers are continuously being commercially developed, and various polymers having, for example, different combinations of identical or similar repeating units, different relative ratios of comonomers, and / or different molecular weights are continuously being commercially developed.

[0046] In exemplary embodiments, at least one of the one or more polyquaternium polymers is polyquaternium-1. Polyquaternium-1 is either commercially available under the trademark Onamer® M from distributors such as Stepan Inc., or can be synthesized by well-known methods (e.g., see U.S. Patent No. 4,027,020, the contents of which are incorporated herein by reference). Optionally, the polymer may have alternative end groups (e.g., hydroxyallyl, aminoallyl, and diene end groups) (e.g., see U.S. Patent No. 7,705,112, the contents of which are incorporated herein by reference).

[0047] The polyquaternium polymer preferably contains one or more ophthalmologically suitable anionic organic or inorganic counterions. In exemplary embodiments, the preferred counterion is a chloride.

[0048] In some embodiments, the cationic oligomer or polymer is characterized by a charge density that can be determined by methods known in the art (e.g., colloidal titration). In exemplary embodiments, 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.

[0049] In exemplary embodiments, one or more polyquaternium polymers are present in the contact lens treatment solution in an amount ranging from about 0.00001 to about 0.001 wt.% based on the total weight of the contact lens treatment solution. In exemplary embodiments, one or more polyquaternium polymers are present in the contact lens treatment solution in an amount ranging from about 0.00001 to about 0.0005 wt.% based on the total weight of the contact lens treatment solution. In other embodiments, one or more polyquaternium polymers are present in the contact lens treatment solution in an amount ranging from about 0.00002 to about 0.0003 wt.% based on the total weight of the contact lens treatment solution.

[0050] The contact lens treatment solutions disclosed herein further contain one or more additional additives. In non-limiting exemplary embodiments, the contact lens treatment solutions may further contain one or more surfactants. Preferred surfactants include, for example, one or more poloxamers and / or poloxamines. Typical examples of preferred poloxamers are poloxamer block copolymers. One specific type of poloxamer block copolymer is available under the trademark Pluronic (BASF Wyandotte Corp., Wyandotte, Mich.). Poloxamers include Pluronic and reverse Pluronic. Pluronic is a series of ABA block copolymers consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) blocks, generally represented by formula I. HO(C2H4O) a (C3H6O) b (C2H4O) a H (I) Here, a is independently at least 1, and b is at least 1.

[0051] Inverse Pluronic is a series of BAB block copolymers, each consisting of a poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) block, generally represented by formula II. HO(C3H6O) b (C2H4O) a (C3H6O) b H (II) Here, a is at least 1, and b is independently at least 1. Poly(ethylene oxide) (PEO) blocks are hydrophilic, while poly(propylene oxide) (PPO) blocks are hydrophobic. Each series of poloxamers has a different ratio of PEO to PPO, which ultimately determines the hydrophilic-lipophilic balance (HLB) of the material, i.e., different HLB values ​​are based on different 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 exemplary embodiments, the HLB of poloxamers ranges from about 5 to about 24. In other embodiments, the HLB of poloxamers ranges from about 1 to about 5.

[0052] Poloxamers and inverse poloxamers have terminal hydroxyl groups that can be terminally functionalized. An example of a terminally functionalized poloxamer is poloxamerized methacrylate (e.g., Pluronic® F127 dimethacrylate), as disclosed in U.S. Patent Application Publication 2003 / 0044468 and U.S. Patent No. 9,309,357, whose contents are incorporated herein by reference, as described herein. Other examples include glycidyl-terminated copolymers of polyethylene glycol and polypropylene glycol, as disclosed in U.S. Patent No. 6,517,933, whose contents are incorporated herein by reference.

[0053] Poloxamers are functionalized to provide desired reactivity at the molecular terminals. Functionality can vary and is determined based on the intended use of the functionalized PEO-containing block copolymer and PPO-containing block copolymer. That is, the PEO-containing block copolymer and PPO-containing block copolymer are reacted to provide terminal functionality that is complementary to the intended device-forming monomer mixture. The term “block copolymer” as used herein is understood to mean a poloxamer having two or more blocks within its polymer backbone.

[0054] In one embodiment, one or more poloxamers are present in the contact lens treatment solution in an amount ranging from about 0.001 to about 5.0 wt.% based on the total weight of the contact lens treatment solution. In another exemplary embodiment, one or more poloxamers are present in the contact lens treatment solution in an amount ranging from about 0.005 to about 1.0 wt.% based on the total weight of the contact lens treatment solution.

[0055] While poloxamers and inverse poloxamers are considered bifunctional molecules (based on terminal hydroxyl groups), poloxamine is a tetrafunctional molecule; that is, the molecule is a tetrafunctional block copolymer terminated at primary hydroxyl groups and linked by a central diamine. A specific type of poloxamine block copolymer is available under the trademark Tetronic (BASF). Poloxamine includes Tetronic and inverse Tetronics. Poloxamine has the general structure of formula III below. [ka] Here, a is independently at least 1, and b is independently at least 1.

[0056] Poloxamines are functionalized to provide desired reactivity at the molecular terminals. Functionality can vary and is determined based on the intended use of the functionalized PEO-containing block copolymers and PPO-containing block copolymers. That is, the PEO-containing block copolymers and PPO-containing block copolymers are reacted to provide terminal functionality that is complementary to the intended device-forming monomer mixture. The term “block copolymer” as used herein is understood to mean a poloxamine having two or more blocks within its polymer backbone.

[0057] In one embodiment, one or more poloxamines are present in the contact lens treatment solution in an amount ranging from about 0.001 to about 5.0 wt.% based on the total weight of the contact lens treatment solution. In another exemplary embodiment, one or more poloxamines are present in the contact lens treatment solution in an amount ranging from about 0.1 to about 1.2 wt.% based on the total weight of the contact lens treatment solution.

[0058] In one non-limiting exemplary embodiment, the contact lens treatment solution may further contain one or more additional antimicrobial agents. Suitable antimicrobial agents from a preferred ophthalmic viewpoint include, for example, polymer biguanides or their salts or free bases, terpenes or their derivatives, branched glycerol monoalkyl ethers, branched glycerol monoalkylamines, branched glycerol monoalkyl sulfides, fatty acid monoesters (fatty acid monoesters include an aliphatic fatty acid moiety having 6 to 14 carbon atoms and an aliphatic hydroxyl moiety), amidoamine compounds, and combinations thereof. Suitable antimicrobial agents for use herein include chemicals that induce their antimicrobial activity through chemical or physiological interactions with microorganisms. These agents may be used alone or in combination.

[0059] Suitable polymeric biguanide antimicrobial agents include, for example, polymeric hexamethylene biguanides (PHMB) (commercially available from Zeneca, Wilmington, Del.), their polymers, and water-soluble salts. In exemplary embodiments, the water-soluble polymeric biguanides for use herein may have a number-average molecular weight of at least about 1,000, or a number-average molecular weight of about 1,000 to about 50,000. Suitable water-soluble salts of the free base include, for example, hydrochlorides, borates, acetates, glucons, sulfons, tartrates, and citrates. In general, hexamethylene biguanide polymers (also known as polyaminopropyl biguanides (PAPB)) have a number-average molecular weight of up to about 100,000. Such compounds are known and disclosed in U.S. Patent No. 4,758,595, which is incorporated herein by reference.

[0060] PHMB is best described as a polymeric biguanide composition comprising at least three, preferably at least six, biguanide polymers, which are referred to as PHMB-A, PHMB-CG, and PHMB-CGA, and their general chemical structures are shown below. [ka]

[0061] For each of these polymers, "n" represents the average number of repeating groups. In fact, a distribution of polymer lengths will exist for each of the polymers shown. In the prior art synthesis route to PHMB, a polymeric biguanide composition was obtained in which approximately 50% by weight of the polymer composition was PHMB-CGA (i.e., having a cyanoguanidino end cap at one end and an amine at the other), approximately 25% by weight was PHMB-A, and approximately 25% by weight was PHMB-CG. Given this approximate weight ratio of the three main PHMB polymers described above, the proportion of cyanoguanidino end caps is also approximately 50% of the total number of end groups. In this application, this conventional polymeric biguanide composition is referred to as poly(hexamethylene biguanide) or PHMB.

[0062] 13 Polymeric biguanide compositions containing less than about 18 mol% of terminal amine groups, as measured by 13C NMR, can also be used. Polymeric biguanide compositions can also be 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% of terminal amine groups and more than about 40 mol% of terminal guanidine groups. In another embodiment, the biguanide composition contains less than about 18 mol% of terminal amine groups and more than about 55 mol% of terminal guanidine groups.

[0063] This biguanide composition is PHMB-CG *It is said. The polymer biguanide composition is also generally called "hexamethylene biguanide", and as will be understood by those skilled in the art, includes both PHMB and PHMB-CG * both of which are included.

[0064] Suitable terpene antibacterial agents include, for example, any monoterpene, sesquiterpene, and / or diterpene, or derivatives thereof. Acyclic, monocyclic, and / or bicyclic monoterpenes, sesquiterpenes, and / or diterpenes, and those having a greater number of rings can be used. The "derivative" of a terpene, as used herein, is understood to mean a terpene hydrocarbon having one or more functional groups, such as terpene alcohols, terpene ethers, terpene esters, terpene aldehydes, terpene ketones, etc., and combinations thereof. Here, both trans isomers and cis isomers are suitable. In one embodiment, the terpene and the terpene moiety in the derivative can contain 6 to about 100 carbon atoms, or about 10 to about 25 carbon atoms.

[0065] Typical examples of suitable terpene alcohol antibacterial agents include berberinol, trans-pinocarveol, cis-2-pinanol, nopol, isoborneol, carveol, piperitol, thymol, α-terpineol, terpinene-4-ol, menthol, 1,8-terpin, dihydro-terpineol, nerol, geraniol, linalool, citronellol, hydroxycitronellol, 3,7-dimethyloctanol, dihydro-myrsenol, tetrahydro-alloocimenol, perillyl alcohol, faradiol, etc., and mixtures thereof.

[0066] Typical examples of suitable terpene ethers and terpene ester antimicrobial agents include 1,8-cineole, 1,4-cineole, isobornyl methyl ether, rosepyran, α-terpinyl methyl ether, menthofuran, trans-anethole, methyl chavicol, allocymenediepoxide, limonene monoepoxide, isobornyl acetate, nonyl acetate, α-terpinyl acetate, linalyl acetate, geranyl acetate, citronellyl acetate, dihydroterpinyl acetate, meryl acetate, and mixtures thereof.

[0067] Typical examples of terpene aldehydes and terpene ketone antimicrobial agents include myrthenal, camphorenaldehyde, perillaldehyde, citronellal, citral, hydroxycitronellal, camphor, verbenone, carbenone, dihydrocarbone, carvone, piperitone, menthone, geranylacetone, pseudoionone, α-ionine, iso-psoid-methylionone, n-psoid-methylionone, isomethylionone, n-methylionone, and mixtures thereof. Any other terpene hydrocarbons having functional groups known in the art may be used herein in the compositions of the present invention.

[0068] In exemplary embodiments, suitable terpenes or their derivatives as antimicrobial agents include, but are not limited to, tricyclene, α-pinene, terpinolene, carveol, amyl alcohol, nerol, β-santalol, citral, pinene, nerol, β-ionone, caryophyllene (derived from clove), guaiol, anisaldehyde, cedrol, linalool, d-limonene (orange essential oil, lemon essential oil), longiphorene, anisyl alcohol, patchouli alcohol, α-cadinene, 1,8-cineole, ρ-cymene, 3-carene, ρ-8-menthane, trans-menthone, borneol, α-phencol, iso It contains amyl acetate, terpine, cinnamaldehyde, ionone, geraniol (derived from rose and other flowers), myrcene (derived from bayberry wax, laurel and verbena essential oils), nerol, citronellol, carvacrol, eugenol, carvone, α-terpineol, anethole, camphor, menthol, limonene, nerolidol, farnesol, phytol, carotene (vitamin A1), squalene, thymol, tocotrienol, periryl alcohol, borneol, cymene, carene, terpenene, linalool, 1-terpene-4-ol, zingiberene (derived from ginger), and mixtures thereof.

[0069] In exemplary embodiments, a preferred branched glycerol monoalkyl ether antimicrobial agent is 3-[(2-ethylhexyl)oxy]-1,2-propanediol (EHOPD). In another embodiment, a preferred branched glycerol monoalkylamine antimicrobial agent is 3-[(2-ethylhexyl)amino]-1,2-propanediol (EHAPD). In yet another embodiment, a preferred branched glycerol monoalkyl sulfide antimicrobial agent is 3-[(2-ethylhexyl)thio]-1,2-propanediol (EHSPD). In yet another embodiment, the ophthalmic composition comprises a mixture of any one of the antimicrobial agents EHOPD, EHAPD, and EHSPD. The chemical structures of EHOPD, EHAPD, and EHSPD are shown below. [ka]

[0070] EHOPD, also known as octoxyglycerin, is sold under the trademark name Sensiva® SC50 (Schulke & Mayr). EHOPD is a branched glycerol monoalkyl ether, gentle on the skin, and known to exhibit antibacterial activity against various Gram-positive bacteria, such as Icrococcus luteus, Corynebacterium aquaticum, Corynebacterium flavescens, Corynebacterium callunae, and Corynebacterium nephredi. Therefore, EHOPD is used in various skin deodorant preparations at concentrations of approximately 0.2–3 weight percent. EHAPD can be prepared from 2-ethylhexylamine and 2,3-epoxy-1-propanediol using chemistry well known to those skilled in the art. EHSPD can be prepared from 2-ethylhexylthiol and 2,3-epoxy-1-propanediol using chemistry well known to those skilled in the art.

[0071] Suitable fatty acid monoester antimicrobial agents include, for example, fatty acid monoesters comprising an aliphatic fatty acid moiety and an aliphatic hydroxyl moiety having 6 to 14 carbon atoms. The term “aliphatic” refers to a linear or branched saturated or unsaturated hydrocarbon having 6 to 14 carbon atoms. In exemplary embodiments, the aliphatic fatty acid moiety is a linear saturated or unsaturated hydrocarbon with 8 to 10 carbon atoms. In another embodiment, the aliphatic fatty acid moiety is a branched saturated or unsaturated hydrocarbon with 8 to 10 carbon atoms.

[0072] The aliphatic hydroxyl moiety of the fatty acid monoester can be any aliphatic compound having at least one hydroxyl group. In addition, the aliphatic hydroxyl moiety can have 3 to 9 carbon atoms. The aliphatic hydroxyl moiety can, without limitation, include propylene glycol, glycerol, polyalkylene glycols, such as polyethylene glycol or polypropylene glycol, cyclic polyols, such as sorbitan, glucose, mannose, sucrose, fructose, fucose, and inositol and their derivatives, as well as linear polyols, such as mannitol and sorbitol and their derivatives, and mixtures thereof.

[0073] Suitable amidoamine antimicrobial agents include, for example, amidoamines of the following general formulas: R 15 -(OCH2CH2) m -X-(CH2) n -Y Here, R 15 C6-C 30 X is a saturated or unsaturated hydrocarbon, for example, a linear or branched substituted or unsubstituted alkyl, alkylaryl, or alkoxyaryl group, where m is 0 to 16 and n is 2 to 16. X is -C(O)-NR 16 -or -R 16 NC(O)-, and Y is -N(R 17 )2, R 16 and R 17 Each of these is independently hydrogen, a C1-C8 saturated or unsaturated alkyl or hydroxyalkyl group, or a pharmaceutically acceptable salt thereof.

[0074] As will be readily apparent to those skilled in the art, some of the amide amines used in the contact lens treatment solutions disclosed herein are commercially available. For example, myristamidopropyl dimethylamine is commercially available from Alcon Inc. (Fort Worth, Tx.) under the trademark Aldox®. Lauramidopropyl dimethylamine is commercially available from Inolex Chemical Company (Philadelphia, Pa.) under the trademark LEXAMINE® L-13. Stearamidopropyl dimethylamine is also commercially available from Inolex Chemical Company as LEXAMINE® S-13. The aforementioned amide amines can be synthesized according to known techniques, including those described in U.S. Patent No. 5,573,726, the content of which is incorporated herein by reference.

[0075] In one non-limiting exemplary embodiment, the one or more antimicrobial agents described above may be used in an amount that at least partially reduces the microbial population in the contact lens treatment solution used. If necessary, one or more antimicrobial agents may be used in a disinfectant amount, which reduces the microbial bioburden by, for example, two log-orders of magnitude in four hours and / or one log-order of magnitude in one hour. In one non-limiting exemplary embodiment, the disinfectant amount is the amount that eliminates the microbial load on the contact lens when used in a regimen for the recommended immersion time (FDA Chemical Disinfection Efficacy Test-July, 1985 Contact Lens Solution Draft Guidelines).

[0076] In one embodiment, one or more additional antimicrobial agents are present in the contact lens treatment solution in an amount ranging from about 0.00005 to about 0.15 wt.% based on the total weight of the contact lens treatment solution. In another exemplary embodiment, one or more antimicrobial agents are present in the contact lens treatment solution in an amount ranging from about 0.0001 to about 0.001 wt.% based on the total weight of the contact lens treatment solution.

[0077] In one non-limiting exemplary embodiment, the contact lens treatment solution disclosed herein may further contain one or more polysaccharides. In exemplary embodiments, the polysaccharides include anionic polysaccharides. Suitable anionic polysaccharides include, for example, hyaluronic acid or its salts, such as sodium hyaluronate or potassium hyaluronate, chondroitin sulfate, chitosan, aloe vera, and carboxymethylcellulose. In exemplary embodiments, the polysaccharides include nonionic polysaccharides. Suitable nonionic polysaccharides include, for example, hemicellulose, hydroxypropyl methylcellulose, methylcellulose, and ethylcellulose.

[0078] In exemplary embodiments, one or more polysaccharides are present in the contact lens treatment solution in an amount ranging from about 0.01 to about 0.02 wt.% based on the total weight of the contact lens treatment solution.

[0079] In one non-limiting exemplary embodiment, the contact lens treatment solution may further contain one or more comforting agents. Suitable comforting agents include, for example, polyols, antioxidants, and complex carbohydrates. Suitable polyols include, for example, glucose, mannitol, erythritol, sorbitol, polyvinyl alcohol, maltose, glycerol, and treherose. Suitable antioxidants include, for example, alpha-tocopherol and other water-soluble vitamin E moieties, ascorbic acid, ascorbyl glucoside, cysteine, carnosol, carnitine, epicatechin, gallic acid, resveratrol, ellagic acid, pycnogel, lycopene, astaxanthin, coenzyme Q10, caffeic acid, hydroquinone monomethyl ether, and butylated hydroxytoluene. Suitable complex carbohydrates include, for example, tremella polysaccharides and carboxymethylcellulose.

[0080] In one embodiment, one or more comforting agents are present in the contact lens treatment solution in an amount ranging from about 0.1 to about 2.0 wt.% based on the total weight of the contact lens treatment solution. In another exemplary embodiment, one or more comforting agents are present in the contact lens treatment solution in an amount ranging from about 0.2 to about 1.5 wt.% based on the total weight of the contact lens treatment solution.

[0081] The contact lens treatment solutions disclosed herein may further contain one or more other components commonly present in contact lens treatment solutions. In non-limiting exemplary embodiments, the contact lens treatment solutions disclosed herein may further contain, for example, chelating agents, tonicity modifiers, buffering agents, pH modifiers, viscosity modifiers, lubricants, etc., which help to make the contact lens treatment solution more comfortable for the user and / or more effective for its intended use.

[0082] In exemplary embodiments, one or more suitable chelating components can be used to help remove lipid and protein deposits from the lens surface after daily use. Typically, the contact lens treatment solution contains a relatively small amount, for example, about 0.005% to about 0.20 (w / v) of ethylenediaminetetraacetic acid (EDTA) or its corresponding metal salt (e.g., disodium salt, Na2EDTA).

[0083] Suitable tonic modifiers include, for example, glucose, calcium, and magnesium chloride, and mixtures thereof. These tonic modifiers are typically used individually in amounts ranging from about 0.01 to about 2.5% w / v. In one embodiment, the tonic modifier is used in amounts ranging from about 0.2 to about 1.5% w / v. The tonic agent can be used in an amount that provides a final effective osmotic value of at least about 150 mOsm / kg. In an exemplary embodiment, the tonic modifier is used in an amount that provides a final effective osmotic value of about 150 to about 420 mOsm / kg. In an exemplary embodiment, the tonic modifier is used in an amount that provides a final effective osmotic value of about 150 to about 350 mOsm / kg. In an exemplary embodiment, the tonic modifier is used in an amount that provides a final effective osmotic value of about 160 to about 320 mOsm / kg.

[0084] In non-limiting exemplary embodiments, the contact lens treatment solution disclosed herein contains a borate buffer in an amount of less than 0.3 wt.%. In one non-limiting exemplary embodiment, the contact lens treatment solution disclosed herein does not contain a borate buffer. In another non-limiting exemplary embodiment, the contact lens treatment solution disclosed herein does not contain a sodium salt buffer (e.g., NaCl). In another non-limiting exemplary embodiment, the contact lens treatment solution disclosed herein contains a borate buffer in an amount of less than 0.3 wt.% and does not contain a sodium salt buffer (e.g., NaCl). In yet another non-limiting exemplary embodiment, the contact lens treatment solution disclosed herein does not contain a borate buffer or a sodium salt buffer (e.g., NaCl).

[0085] In non-limiting exemplary embodiments, the contact lens treatment solutions disclosed herein can be formulated for direct application to the eye, including, for example, eye drops, re-moistening eye drops for re-moistening contact lenses while they are being worn, and also suitable as multipurpose solutions. In non-limiting exemplary embodiments, the contact lens treatment solutions disclosed herein can be formulated as compositions for indirect application to the eye, for example, as contact lens treatment solutions for treating contact lenses before they are worn in the eye, or as storage solutions for storing lenses.

[0086] The contact lens treatment solution in the exemplary embodiment is physiologically compatible. Specifically, the contact lens treatment solution must be "ophthalmologically safe" for use with contact lenses; that is, contact lenses treated with the contact lens treatment solution are generally suitable and safe for direct insertion onto the eye without rinsing; that is, the contact lens treatment solution is safe and comfortable for daily contact with the eye via contact lenses moistened with the solution. The tonicity and pH of the ophthalmologically safe composition are suitable for the eye and contain materials and amounts thereof that are non-cytotoxic in accordance with ISO (International Organization for Standardization) standards and U.S. Food and Drug Administration (FDA) regulations. The composition must be sterile in the sense that the absence of microbial contaminants in the product before launch must be statistically demonstrated to the extent required for such a product.

[0087] In exemplary embodiments, the pH of the contact lens treatment solution disclosed herein may be maintained within the range of about 4.0 to about 9.0, or about 5.0 to about 8.0, or about 6.0 to about 8.0, or about 6.5 to about 7.8. In another exemplary embodiment, the pH of the contact lens treatment solution disclosed herein may be about 7 or higher.

[0088] In exemplary embodiments, the osmotic pressure of the contact lens treatment solution disclosed herein may be in the range of at least about 150 mOsm / kg, or at least about 200 mOsmol / kg, and up to about 420 mOsmol / kg. In another exemplary embodiment, the osmotic pressure of the contact lens treatment solution disclosed herein may be in the range of about 150 to about 420 mOsm / kg. In another exemplary embodiment, the osmotic pressure of the contact lens treatment solution disclosed herein may be in the range of about 150 to about 350 mOsm / kg. In another exemplary embodiment, the osmotic pressure of the contact lens treatment solution disclosed herein may be in the range of about 160 to about 320 mOsm / kg. In an exemplary embodiment, the osmotic pressure of the contact lens treatment solution disclosed herein may be in the range of about 300 to about 400 mOsm / kg. In another exemplary embodiment, the osmotic pressure of the contact lens treatment solution disclosed herein may be in the range of about 350 to about 400 mOsm / kg. The contact lens treatment solution is substantially isotonic or hypertonic (e.g., slightly hypertonic) and acceptable from an ophthalmic standpoint.

[0089] In non-limiting exemplary embodiments, the contact lens treatment solutions disclosed herein may be formulated as “multipurpose solutions.” Multipurpose solutions are useful for cleaning, disinfecting, storing, and rinsing lenses, particularly soft contact lenses. Multipurpose solutions do not preclude the possibility that some wearers (e.g., those particularly sensitive to chemical disinfectants or other chemicals) may prefer to rinse or moisten their contact lenses with another solution (e.g., sterile saline solution) before wearing them. The term “multipurpose solution” also does not preclude the possibility of a routine cleaning agent not used daily or an auxiliary cleaning agent for further protein removal (e.g., an enzymatic cleaning agent typically used weekly). The term “cleaning” means that the solution contains one or more agents in a concentration sufficient to loosen and remove loosely retained lens deposits and other contaminants from the surface of the contact lens, which may be used in combination with finger manipulation (e.g., manually rubbing the lens with the solution) or with an accessory device (e.g., a mechanical cleaning aid) that comes into contact with the lens and agitates the solution.

[0090] Conventionally, commercially available multipurpose solutions required regimens involving mechanically rubbing lenses with the multipurpose solution to provide the necessary disinfection and cleaning. Such regimens are required under government regulatory authorities (e.g., the FDA) for chemical disinfection systems that are not qualified as chemical disinfection solutions. In exemplary embodiments, a cleaning and disinfecting solution can be formulated that, on the one hand, provides improved cleaning and disinfection, and on the other hand, is sufficiently gentle on the eyes for use as a wetting agent (e.g., eye drops). In another exemplary embodiment, the contact lens treatment solution disclosed herein is formulated to meet the requirements of FDA or ISO standalone procedures for contact lens disinfection products.

[0091] Accordingly, in non-limiting exemplary embodiments, a method for cleaning and disinfecting contact lenses includes immersing the contact lenses in the contact lens treatment solutions disclosed herein for a period of time sufficient to clean and disinfect the contact lenses. Preferred periods may include, for example, at least about 30 seconds, or about 2 to about 12 hours, or about 2 to about 4 hours.

[0092] In exemplary embodiments, for example, a rubbing protocol can be used which involves adding a few drops of the contact lens treatment solution disclosed herein to both sides of the lens, followed by gently rubbing the surface between the fingers for about 3 to about 10 seconds. The lens can then be optionally rinsed and subsequently immersed in the contact lens treatment solution in the lens storage case for a suitable time (e.g., several minutes or several hours, e.g., at least 2 hours). The lens is then removed from the lens storage case and put back into place on the eye.

[0093] The type of contact lens to be brought into contact with the contact lens processing solution disclosed herein is not important, and any contact lens is possible. Typical 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 oxygen-permeable lens materials, etc.), rigid oxygen-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 does not break when bent. Any known material for producing contact lenses can be used herein. For example, the contact lens processing solution can be used with (1) hard lenses formed from materials prepared by polymerization of acrylic acid esters (e.g., 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 (e.g., silicone hydrogels) (hydrogels are defined as crosslinked polymer systems containing water in equilibrium).

[0094] Generally, hydrogels exhibit excellent biocompatibility, meaning they are biologically or biochemically compatible by not causing toxicity, injury, or immunological reactions in living tissues. Typical conventional hydrogel contact lens materials are made by polymerizing a monomer mixture containing at least one hydrophilic monomer (e.g., (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 from which the copolymer is prepared further contains silicone-containing monomers in addition to the hydrophilic monomers. Generally, the monomer mixture also contains crosslinking monomers (e.g., ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, and methacrylateoxyethyl vinyl carbonate). Alternatively, either the silicone-containing monomer or the hydrophilic monomer may function as a crosslinking agent. [Examples]

[0095] The following embodiments are provided to enable those skilled in the art to practice the invention and are merely illustrative. The embodiments should not be construed as limiting the scope of the exemplary embodiments set forth in the claims. The following abbreviations are used in the embodiments.

[0096] TRIS: Tromethamine buffer.

[0097] Bis-Tris: Bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane.

[0098] Na2EDTA: Disodium ethylenediaminetetraacetate salt

[0099] AMP-95: 95% aqueous solution of 2-amino-2-methyl-1-propanol.

[0100] PAPB: Polyaminopropyl biguanide.

[0101] Polyquaternium-1: A polyquaternium polymer represented by the following structure: [ka]

[0102] Examples 1-4 and Comparative Examples A-E The contact lens treatment solution was prepared by mixing the following components listed in Table 1. [Table 1]

[0103] Comparative Examples A-E The contact lens treatment solution was prepared by mixing the following components listed in Table 2. [Table 2]

[0104] test The degradation of PQ-1 was evaluated by comparing the disinfection effects of both non-autoclaved and autoclaved aqueous solutions. Autoclaving was performed at 121°C for 30 minutes. The contact lens treatment solutions of Examples 1-4 and Comparative Examples A-E were tested in a modified ISO 14729 test evaluating disinfection time of 4 hours, and their efficacy against three bacterial species (Staphylococcus aureus (Sa), Pseudomonas aeruginosa (Pa), and Serratia marcescens (Sm)) and one fungal species (Fusarium solani (Fs)) was determined using 10% organic soil.

[0105] Individual sterilization tests were performed as follows: Microbial challenge inoculum were prepared using Staphylococcus aureus (ATCC6538), Pseudomonas aeruginosa (ATCC9027), Serratia marcescens (ATCC13880), and Fusarium solani (ATCC36031). The challenge microorganisms were transferred to recommended agar plates and cultured for the appropriate duration and temperature. The cultures were collected using sterile Dulbecco's phosphate-buffered saline plus 0.05% w / v polysorbate 80 (DPBST) or a suitable diluent and transferred to suitable containers. The spore suspension was filtered through sterile glass wool to remove hyphae. Serratia marcescens was filtered through a 1.2 μm filter, if necessary, to make the suspension clear. After collection, the suspensions were centrifuged at a temperature of 20-25°C for a maximum of 30 minutes, not exceeding 5000xg. Decant the supernatant and dilute with DPBST or other suitable diluent 1X10 7 ~1X10 8 The water was resuspended in cfu / ml.

[0106] The appropriate microbial concentration may be estimated, for example, by measuring the turbidity of the suspension using a spectrophotometer at a pre-selected wavelength (e.g., 490 nm). One test tube was prepared, containing at least 10 mL of the test solution per challenge organism. Inoculum controls (ICs) were prepared by dispersing the same aliquot of inoculum as the test sample in a suitable diluent (DPBST). The ICs for each challenge microorganism were serially diluted and cultured on appropriate agar plates at the start of the test (T=0). Each test tube of the solution to be tested was filled with a final count of 1 x 10⁶. 5 ~1x10 6A suspension of the test microorganism was inoculated to a level sufficient to achieve cfu / mL. The amount of inoculant did not exceed 1 percent of the sample volume. The inoculant was thoroughly dispersed by mixing the sample (e.g., by vortexing each test tube for at least 5 seconds). The inoculated products were stored at 20-25°C. After disinfection for a certain period, aliquots of 1.0 mL of the inoculated product were taken to determine the viable count.

[0107] The suspension was thoroughly mixed by vigorously vortexing for at least 5 seconds. 1.0 mL aliquots taken at specified time intervals were subjected to a suitable series of 10-fold dilutions in a suitable neutralizing medium. The suspension was vigorously mixed and cultured for a suitable time (at least 10 minutes and not exceeding 1 hour before plate culture) to neutralize the microbial agent. The viable cell count of the microorganisms was determined at appropriate dilutions by preparing dual plates of triptycase soybean agar (TSA) for bacteria and dual plates of Sabouraud glucose agar (SDA) for molds and yeasts. Bacterial recovery plates were cultured at 30–35°C for 2–4 days. Yeast recovery plates were cultured at 20–25°C or 30–35°C for 3–5 days. Mold recovery plates were cultured at 20–25°C for 4–7 days. The average number of colony-forming units (cfus) was determined on a countable plate. A countable plate refers to a plate containing 30-300 cfu for bacteria and yeast, and 8-80 cfu for mold. However, if the colonies are 10 0 or 10 1 Except when observed only in diluted plates. The reduction in microbial activity was then calculated at the specified time point. To demonstrate the suitability of the medium used for growing the test microorganisms and to provide an estimate of the initial inoculum concentration, an inoculum control was prepared by dispersing the same aliquot inoculum in a suitable diluent used to suspend the microorganisms listed above. After inoculation into an effective neutralizing culture medium and incubation for an appropriate period, the inoculum control was 1.0 x 10⁻⁶. 5 ~1.0x10 6 It needs to be cfu / mL.

[0108] Table 3 below shows the logarithmic reduction values ​​of the 4-hour disinfection efficacy test for the contact lens treatment solutions in Examples 1-4 and Comparative Examples A-D. [Table 3] The contact lens treatment solutions of Examples 1-4 showed significantly improved disinfection effects against both bacterial and fungal species after autoclaving compared to the contact lens treatment solutions of Comparative Examples A-E. In addition, Examples 3 and 4 indicate that in order to obtain the desired antibacterial effect, sufficient amounts of one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and their salts, and one or more polyquaternium polymers should be added to the contact lens treatment solution.

[0109] Examples 5 and 6 The contact lens treatment solution was prepared by mixing the following components listed in Table 4. [Table 4]

[0110] Comparative Examples F and G The contact lens treatment solution was prepared by mixing the following components listed in Table 5. [Table 5]

[0111] test The degradation of PQ-1 was evaluated by comparing the disinfectant effects of both non-autoclaved and autoclaved aqueous solutions. Autoclaving was performed at 121°C for 30 minutes. The contact lens treatment solutions of Examples 5 and 6 and Comparative Examples F and G were tested in the aforementioned 4-hour disinfectant efficacy test, evaluating the disinfection time over 4 hours. Their efficacy against three bacterial species (Staphylococcus aureus (Sa), Pseudomonas aeruginosa (Pa), and Serratia marcescens (Sm)) and one fungal species (Fusarium solani (Fs))) was determined using 10% organic soil. The results of the disinfectant efficacy screen are shown in Table 6 below. [Table 6]

[0112] The contact lens treatment solutions of Examples 5 and 6 showed significantly improved disinfection effects against bacteria and fungal species after autoclaving, compared to the contact lens treatment solutions of Comparative Examples F and G.

[0113] According to an aspect of the present invention, the contact lens treatment solution comprises (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers.

[0114] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains tris(hydroxymethyl)aminomethane or a salt thereof as component (a).

[0115] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane as component (a).

[0116] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, in an amount of about 0.05 to about 2.0 wt.% based on the total weight of the contact lens treatment solution, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers, in an amount of about 0.00001 to about 0.0010 wt.% based on the total weight of the contact lens treatment solution.

[0117] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane, and salts thereof, in an amount of about 0.1 to about 1.0 wt.% based on the total weight of the contact lens treatment solution, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers, in an amount of about 0.00002 to about 0.0003 wt.% based on the total weight of the contact lens treatment solution.

[0118] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, one or more polyquaternium polymers contain about 30 to about 50,000 quaternary amine functional repeating units.

[0119] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, one or more polyquaternium polymers have a weight-average molecular weight Mw of about 3,000 to about 5,000,000.

[0120] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, one or more polyquaternium polymers have a weight-average molecular weight Mw of about 5,000 to about 40,000.

[0121] In one or more further exemplary embodiments, one or more polyquaternium polymers are cationic, as can be combined with the preceding paragraph.

[0122] In one or more further exemplary embodiments, the polyquaternium polymer comprises polyquaternium-1, as can be combined with the preceding paragraph.

[0123] In one or more further exemplary embodiments, the contact lens treatment solution further comprises one or more surfactants, as may be combined with the preceding paragraph.

[0124] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, one or more surfactants are selected from the group consisting of poloxamers, poloxamines, and mixtures thereof.

[0125] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, poloxamer is at least one of poloxamerge (meth)acrylate and reverse poloxamerge (meth)acrylate, and poloxamine is at least one of poloxamine di(meth)acrylate and reverse poloxamine di(meth)acrylate.

[0126] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, poloxamer is present in the contact lens treatment solution in an amount ranging from about 0.001 to about 5.0 wt.% based on the total weight of the contact lens treatment solution, and poloxamine is present in the contact lens treatment solution in an amount ranging from about 0.001 to about 5.0 wt.% based on the total weight of the contact lens treatment solution.

[0127] In one or more further exemplary embodiments, the contact lens treatment solution further comprises one or more additional antimicrobial agents, as may be combined with the preceding paragraph.

[0128] In one or more further exemplary embodiments, one or more additional antimicrobial agents may be selected from the group consisting of polymer biguanides or salts thereof or free bases, terpene compounds, branched glycerol monoalkyl ethers, branched glycerol monoalkylamines, branched glycerol monoalkyl sulfides, fatty acid monoesters (fatty acid monoesters comprising an aliphatic fatty acid moiety having 6 to 14 carbon atoms and an aliphatic hydroxyl moiety), amidoamine compounds, and combinations thereof.

[0129] In one or more further exemplary embodiments, the contact lens treatment solution further comprises one or more comforting agents, as may be combined with the preceding paragraph.

[0130] In one or more further exemplary embodiments, one or more comforting agents are selected from the group consisting of polyols, antioxidants, and complex carbohydrates, as can be combined with the preceding paragraph.

[0131] In one or more further exemplary embodiments, the polyol is one or more of glycerol and erythritol, as can be combined with the preceding paragraph.

[0132] In one or more further exemplary embodiments, the contact lens treatment solution further comprises one or more polysaccharides, as may be combined with the preceding paragraph.

[0133] In one or more further exemplary embodiments, as can be combined with the preceding paragraph, one or more polysaccharides include one or more anionic polysaccharides and nonionic polysaccharides.

[0134] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, 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.

[0135] In one or more further exemplary embodiments, the contact lens treatment solution may be combined with the preceding paragraph to further include one or more chelating agents, tonicity modifiers, buffering agents, pH modifiers, viscosity modifiers, and lubricants.

[0136] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution contains a borate buffer in an amount of less than 0.3 wt.%.

[0137] In one or more further exemplary embodiments, the contact lens treatment solution does not contain a borate buffer, as may be combined with the preceding paragraph.

[0138] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution is in the form of an eye care or contact lens care product selected from the group consisting of eye drops, contact lens storage solutions, contact lens cleaning solutions, and contact lens multipurpose solutions.

[0139] In one or more further exemplary embodiments, as may be combined with the preceding paragraph, the contact lens treatment solution is in the form of a multipurpose solution or a re-wetting eye drop.

[0140] According to another aspect of the present invention, a method for cleaning and disinfecting contact lenses comprises immersing the contact lenses for a time sufficient to clean and disinfect them in a contact lens treatment solution, which may be combined with the preceding paragraph, comprising (a) one or more tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane, and salts thereof, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers.

[0141] According to yet another exemplary embodiment, a method for inhibiting bacterial adhesion to the surface of a contact lens includes contacting the surface of the contact lens with a contact lens treatment solution according to one or more of the exemplary embodiments, which may be combined with the preceding paragraph, comprising (a) one or more tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, and (b) one or more antimicrobial agents comprising one or more polyquaternium polymers.

[0142] While compositions and methods are described using the term "comprising" various components or steps, unless otherwise stated, compositions and methods may also "essentially consist of" or "consist of" various components or steps.

[0143] The terms “a,” “an,” and “the” are intended to include multiple alternatives (e.g., at least one). The terms “including,” “with,” and “having” are, as used herein, defined as “comprising” (i.e., open language) unless otherwise specified.

[0144] Various numerical ranges are disclosed herein. When an applicant discloses or claims any kind of range, the applicant's intent is, unless otherwise specified, to disclose or claim each numerical value that such a range could reasonably encompass, including the endpoints of the range, as well as any subranges and combinations of subranges that are contained therein. For example, the endpoints of all numerical values ​​in the ranges disclosed herein are approximate unless otherwise excluded by a proviso.

[0145] In this specification, values ​​or ranges may be expressed as "approximately" from one particular value to and / or "approximately" another particular value. Where such values ​​or ranges are expressed, other embodiments disclosed include a list of specific values ​​from one particular value to and / or other specific values. Similarly, where values ​​are expressed as approximations, it will be understood that by using the preceding "approximately," that particular value forms another embodiment. It will be understood that there are several values ​​disclosed therein, and each value is disclosed herein not only as the value itself but also "approximately" that particular value. In another aspect, the use of the term "approximately" means ±20%, ±15%, ±10%, ±5%, ±3%, or ±1% of the stated value.

[0146] If, for any reason, for example, to take into account references that the applicant may not be aware of at the time of filing, the applicant chooses not to claim the entire scope of the Disclosure but only a portion thereof, the applicant reserves the right to exclude or omit any individual element (including any sub-scope or combination of sub-scopes within the group) of any such value or scope that could be claimed in accordance with the scope or in any similar manner. Furthermore, the applicant reserves the right to exclude or omit any element of any claimed group thereof.

[0147] Various features of the composition are described in the context of a single embodiment for the sake of simplicity, but may be provided separately or in any preferred partial combination. All combinations of embodiments are specifically encompassed by the exemplary embodiments disclosed herein, as if every possible combination were individually and expressly disclosed. In addition, all partial combinations enumerated in embodiments describing such variables are also specifically encompassed by the compositions of the present invention and are disclosed herein as if every possible such partial combination were individually and expressly disclosed herein.

[0148] It is 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 an example of preferred embodiments. For example, the functions described above and implemented as the best mode for operating the invention are for illustrative purposes only. Other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of the invention. Furthermore, those skilled in the art will recall other biases within the scope and spirit of the additional features and advantages provided herein.

Claims

1. (a) one or more of tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and salts thereof, (b) A contact lens treatment solution comprising one or more antimicrobial agents containing one or more polyquaternium polymers.

2. The contact lens treatment solution according to claim 1, wherein component (a) is tris(hydroxymethyl)aminomethane or a salt thereof.

3. (a) One or more of the above tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and their salts, in an amount of about 0.05 to about 2.0 wt.% based on the total weight of the contact lens treatment solution. (b) The contact lens treatment solution according to claim 1 or 2, comprising one or more antimicrobial agents containing one or more polyquaternium polymers in an amount of about 0.00001 to about 0.0010 wt.% based on the total weight of the contact lens treatment solution.

4. (a) One or more of the above tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane, and their salts, in an amount of about 0.1 to about 1.0 wt.% based on the total weight of the contact lens treatment solution. (b) The contact lens treatment solution according to claim 1 or 2, comprising one or more antimicrobial agents containing one or more polyquaternium polymers in an amount of about 0.00002 to about 0.0003 wt.% based on the total weight of the contact lens treatment solution.

5. The contact lens treatment solution according to any one of claims 1 to 4, wherein the one or more polyquaternium polymers comprises about 30 to about 50,000 quaternary amine functional repeating units.

6. The contact lens treatment solution according to any one of claims 1 to 5, wherein the one or more polyquaternium polymers have a weight-average molecular weight Mw of about 3,000 to about 5,000,000.

7. The contact lens treatment solution according to any one of claims 1 to 5, wherein the one or more polyquaternium polymers have a weight-average molecular weight Mw of about 5,000 to about 40,000.

8. The contact lens treatment solution according to any one of claims 1 to 7, wherein one or more of the polyquaternium polymers are cationic.

9. The contact lens treatment solution according to any one of claims 1 to 8, wherein the one or more polyquaternium polymers comprises polyquaternium-1.

10. A contact lens treatment solution according to any one of claims 1 to 9, further comprising one or more surfactants.

11. The contact lens treatment solution according to claim 10, wherein the one or more surfactants are selected from the group consisting of poloxamers, poloxamines, and mixtures thereof.

12. The contact lens treatment solution according to claim 11, wherein the poloxamer is present in the contact lens treatment solution in an amount ranging from 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 ranging from about 0.001 to about 5.0 wt.% based on the total weight of the contact lens treatment solution.

13. A contact lens treatment solution according to any one of claims 1 to 12, further comprising one or more additional antibacterial agents.

14. The contact lens treatment solution according to claim 13, wherein the one or more further antibacterial agents are polymer biguanides or their salts or free bases, terpene compounds, branched glycerol monoalkyl ethers, branched glycerol monoalkylamines, branched glycerol monoalkyl sulfides, and fatty acid monoesters, wherein the fatty acid monoester is selected from the group consisting of fatty acid monoesters, amidoamine compounds, and combinations thereof, comprising an aliphatic fatty acid moiety having 6 to 14 carbon atoms and an aliphatic hydroxyl moiety.

15. A contact lens treatment solution according to any one of claims 1 to 14, further comprising one or more comforting agents.

16. The contact lens treatment solution according to claim 15, wherein the one or more comforting agents are selected from the group consisting of polyols, antioxidants, and complex carbohydrates.

17. The contact lens treatment solution according to claim 16, wherein the polyol is one or more of glycerol and erythritol.

18. A contact lens treatment solution according to any one of claims 1 to 17, further comprising one or more polysaccharides.

19. The contact lens treatment solution according to claim 18, wherein the one or more polysaccharides include one or more anionic polysaccharides and nonionic polysaccharides.

20. The contact lens treatment solution according to claim 19, wherein 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.

21. A contact lens treatment solution according to any one of claims 1 to 20, further comprising one or more of a chelating agent, a tonicity modifier, a buffering agent, a pH adjuster, a viscosity modifier, and a lubricant.

22. The contact lens treatment solution according to any one of claims 1 to 21, wherein the contact lens treatment solution contains a borate buffer in an amount of less than 0.3 wt.%.

23. The contact lens treatment solution according to any one of claims 1 to 22, wherein the contact lens treatment solution does not contain a borate buffer.

24. A contact lens treatment solution according to any one of claims 1 to 23, in the form of an eye care or contact lens care product selected from the group consisting of eye drops, contact lens storage solutions, contact lens cleaning solutions, and multipurpose contact lens solutions.

25. A contact lens treatment solution according to any one of claims 1 to 23, in the form of a multipurpose solution or a re-wetting eye drop.

26. A method for cleaning and disinfecting contact lenses, comprising immersing the contact lenses in a contact lens treatment solution according to any one of claims 1 to 25 for a time sufficient to clean and disinfect the contact lenses.

27. A method for suppressing the adhesion of bacteria to the surface of a contact lens, comprising bringing the surface of the contact lens into contact with a contact lens treatment solution according to any one of claims 1 to 25.

26. Use of the contact lens treatment solution according to any one of claims 1 to 25 for cleaning and disinfecting contact lenses.

27. Use of the contact lens treatment solution according to any one of claims 1 to 25 for suppressing the adhesion of bacteria to the surface of a contact lens.

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