Ophthalmic composition

Abstract

An ophthalmic composition according to the present invention contains (A) 0.01-0.5 w / w% of a copolymer having constituent units represented by formula (1a) to formula (1c), where the molar ratio of each constituent unit is a:b:c=100:10-400:2-50 and the weight average molecular weight is 5,000-2,000,000, (B) 0.000001-0.0001 w / w% of polyhexamethylene biguanide represented by formula (2) or a salt thereof, and (C) 0.02-5.0 w / w% of polyoxyethylene hydrogenated castor oil and / or (D) 0.02-5.0 w / w% of polyoxyethylene glycol monostearate.　According to the present invention, it is possible to provide an ophthalmic composition that exhibits sufficient preservation efficacy and has high lubricity.

Description

Ophthalmic composition

[0001] This invention relates to ophthalmic compositions.

[0002] Generally, eye drops are used repeatedly over several weeks after opening, so preservatives such as benzalkonium chloride and polyhexamethylene biguanide are added to prevent bacterial contamination within the container. In addition to preservatives, eye drops also contain various additives such as isotonic agents, buffers, and stabilizers. Therefore, even when preservatives are combined with other additives, the preservatives must maintain sufficient preservation effectiveness.

[0003] In recent years, the number of dry eye patients has surged due to factors such as the increase in contact lens wearers and the increased use of smartphones and computers. Dry eye is caused by increased tear evaporation and friction between the conjunctiva and the eye surface during blinking. Therefore, eye drops for treating dry eye require high moisturizing properties to suppress tear evaporation and high lubricity to reduce friction during blinking. Typically, humectants and thickeners are added to improve moisturizing and lubrication properties.

[0004] To date, technologies have been reported that improve the moisturizing and lubricating properties of eye drops by incorporating phosphorylcholine group-containing polymers. For example, Patent Document 1 discloses an eye drop containing a phosphorylcholine group-containing polymer and polyhexamethylene biguanide. Using the eye drop described in Patent Document 1 provides sufficient preservative effect, spreads quickly on the surface of the eye or contact lens, and exhibits moisturizing and lubricating effects.

[0005] Japanese Patent Publication No. 2021-20856 Japanese Patent Publication No. 2022-075857

[0006] Patent Document 1 reports that sufficient lubricity can be imparted to eye drops by incorporating a phosphorylcholine group-containing polymer. However, when polyhexamethylene biguanide is used as a preservative and a sufficient amount of a specific ternary copolymer that significantly contributes to improved lubricity is incorporated, sufficient preservative efficacy may not be obtained. Patent Document 2 discloses a method to improve the reduced preservative efficacy caused by a combination of cationic preservatives and acidic sugars by incorporating eucalyptus oil. However, the combination of polyhexamethylene biguanide and a ternary copolymer containing a phosphorylcholine group is not specified.

[0007] In view of the above problems, the present invention aims to provide an ophthalmic composition that exhibits sufficient preservative effect and has high lubricity.

[0008] As a result of diligent research by the present inventors, we have discovered that an ophthalmic composition containing a copolymer having the constituent units shown in formulas (1a) to (1c) (hereinafter sometimes referred to as "polymer (P)"), that is, a ternary copolymer containing a phosphorylcholine group, a specific preservative, and a specific surfactant in specific proportions exhibits sufficient preservative efficacy and high lubricity, thus completing the present invention.

[0009] In other words, the present invention is as follows: (A) 0.01 w / w% to 0.5 w / w% of a copolymer having constituent units represented by formulas (1a) to (1c), with a molar ratio of each constituent unit being a:b:c = 100:10 to 400:2 to 50, and a weight-average molecular weight of 5,000 to 2,000,000; (B) 0.000001 w / w% to 0.0001 w / w% of polyhexamethylene biguanide represented by formula (2) or a salt thereof; (C) 0.02 w / w% to 5.0 w / w% of polyoxyethylene hydrogenated castor oil and / or (D) 0.02 w / w% to 5.0 w / w% of polyoxyethylene glycol monostearate. [In equations (1a) to (1c), a, b, and c represent the molar ratios of each constituent unit. R １ , R ２ and R ５Each of these independently represents either a hydrogen atom or a methyl group. ３ and R ４ Each of these independently represents a hydrogen atom, a methyl group, or an ethyl group. ６ This represents a monovalent hydrocarbon group with 12 to 24 carbon atoms. [In equation (2), d is a number indicating the repeating unit, and is an integer between 3 and 40.]

[0010] The present invention makes it possible to provide an ophthalmic composition that exhibits sufficient preservative effect and high lubricity.

[0011] The ophthalmic composition of the present invention contains, as component (A), 0.01 / w% to 0.5 w / w% of a copolymer having constituent units represented by formulas (1a) to (1c), with a molar ratio of a:b:c = 100:10 to 400:2 to 50, and a weight-average molecular weight of 5,000 to 2,000,000; as component (B), 0.000001 w / w% to 0.0001 w / w% of polyhexamethylene biguanide or its salt; as component (C), 0.02 w / w% to 5.0 w / w% of polyoxyethylene hydrogenated castor oil; and / or as component (D), 0.02 w / w% to 5.0 w / w% of polyoxyethylene glycol monostearate.

[0012]

[0013] The copolymer (P) used in the ophthalmic composition of the present invention has three constituent units as shown in (1a) to (1c) below, and the molar ratio a:b:c of each constituent unit is 100:10 to 400:2 to 50. <(1) PC constituent unit> The copolymer (P) used in the ophthalmic composition of the present invention has a constituent unit represented by the following formula (1a) (hereinafter sometimes abbreviated as "PC constituent unit"). This PC constituent unit is a constituent unit derived from a PC monomer represented by formula (3) described later. The inclusion of a constituent unit derived from a PC monomer in the copolymer (P) improves its lubricity.

[0014] In the above formula (1a), R １represents a hydrogen atom or a methyl group. "a" represents the proportion of the structural unit represented by the above formula (1a) in the copolymer (P), and represents the molar ratio with the structural units represented by formula (1b) and formula (1c). The PC structural unit in the copolymer (P) is introduced to impart hydrophilicity and the ability to form a hydrogel to the copolymer (P) for improving lubricity. The PC structural unit in the copolymer (P) is obtained from a phosphorylcholine-like group-containing monomer represented by the following formula (3) (hereinafter sometimes abbreviated as a PC monomer) used during the polymerization of the copolymer (P).

[0015] In formula (3), X is a (meth)acryloyloxy group. Note that (meth)acryloyl refers to both methacryloyl and acryloyl. From the perspective of availability, for example, 2-((meth)acryloyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate is preferable as the PC monomer, and further 2-(methacryloyloxy)ethyl-2'-(trimethylammonio)ethyl phosphate represented by the following formula (4) is preferable.

[0016]

[0017] <(2) Amide structural unit> The copolymer (P) used in the ophthalmic composition of the present invention has a structural unit represented by the following formula (1b) (hereinafter sometimes abbreviated as an "amide structural unit").

[0018] In the above formula (1b), R ２ represents a hydrogen atom or a methyl group, and R ３ and R ４ each independently represent a hydrogen atom, a methyl group or an ethyl group. Among them, R ３ and R ４Each of these is preferably independently a methyl group or an ethyl group, and more preferably a methyl group. b represents the proportion of the number of constituent units shown in formula (1b) in the copolymer (P), and represents the molar ratio with the constituent units shown in formulas (1a) and (1c). The amide constituent units in the copolymer (P) are introduced to increase the molecular weight of the copolymer (P) and improve its retention on the corneal surface. Regarding the proportion of amide constituent units in the copolymer (P), when a of the PC constituent units is set to 100, b / a = 10 / 100 or more and 400 / 100 or less, and preferably 30 / 100 or more and 250 / 100 or less. If b is too large, sterile filtration necessary when manufacturing the ophthalmic composition may become difficult, and if it is too small, the effect of improving retention cannot be expected.

[0019] The amide structural units in copolymer (P) are obtained from monomers represented by the following formula (1b') used during polymerization of copolymer (P), namely (meth)acrylamide or (meth)acrylamide derivatives. In other words, the amide structural units are structural units derived from monomers represented by the formula (1b').

[0020] R in equation (1b') ２ , R ３ , R ４ These are R in equation (1b), respectively. ２ , R ３ , R ４ This is the same as above. Examples of (meth)acrylamide or (meth)acrylamide derivatives represented by formula (1b') above include N,N-dimethyl(meth)acrylamide or N,N-diethyl(meth)acrylamide, and N,N-dimethylacrylamide is preferred.

[0021] <(3) Hydrophobic constituent units> The copolymer (P) used in the ophthalmic composition of the present invention has constituent units represented by the following formula (1c) (hereinafter sometimes abbreviated as "hydrophobic constituent units").

[0022] In the above formula (1c), R ５ R represents a hydrogen atom or a methyl group. ６represents a monovalent hydrocarbon group having 12 to 24 carbon atoms, for example, a lauryl group, a stearyl group, or a behenyl group. R ６ is preferably a monovalent hydrocarbon group having 12 to 20 carbon atoms, more preferably 14 to 20 carbon atoms, and even more preferably 17 to 19 carbon atoms. c represents the ratio of the number of structural units represented by the above formula (1c) in the copolymer (P), and represents the molar ratio with the structural units represented by formula (1a) and formula (1b). The hydrophobic structural unit in the copolymer (P) is introduced to enhance the adhesion to corneal cells.

[0023] Regarding the ratio of the hydrophobic structural unit in the copolymer (P), when a of the PC structural unit is 100, c satisfies c / a = 2 / 100 or more and 50 / 100 or less, preferably 5 / 100 or more and 25 / 100 or less. When c is too large, the hydrophilicity of the copolymer (P) decreases, resulting in a decrease in solubility in water and difficulty in manufacturing the ophthalmic composition. When c is too small, the adhesion to corneal cells decreases, and the effect of improving lubricity cannot be expected.

[0024] The hydrophobic structural unit in the copolymer (P) is obtained from a hydrophobic monomer represented by the following formula (1c') used during the polymerization of the copolymer (P). In other words, the hydrophobic structural unit is a structural unit derived from the monomer represented by formula (1c').

[0025] R in formula (1c') ５ and R ６ are the same as R ５ and R ６ in formula (1c), respectively. Examples of the hydrophobic monomer represented by formula (1c') include linear alkyl (meth) acrylates such as lauryl (meth) acrylate, stearyl (meth) acrylate, and behenyl (meth) acrylate, and stearyl methacrylate is preferred.

[0026] Further, the weight average molecular weight of the copolymer (P) is 5,000 to 2,000,000. When the weight average molecular weight is less than 5,000, there may be no expected effect of improving lubricity. When it exceeds 2,000,000, aseptic filtration required for manufacturing the ophthalmic composition may become difficult. Further, from the viewpoint of the effect of improving lubricity, the weight average molecular weight of the copolymer (P) is preferably 10,000 to 1,000,000, and more preferably 50,000 to 500,000. The weight average molecular weight means the value in terms of polyethylene glycol (PEG) measured by gel permeation chromatography (GPC).

[0027] The copolymer (P) represented by the formula (1) has each constitutional unit derived from the formula (1a) to the formula (1c), but the arrangement of each constitutional unit in the copolymer (P) is not particularly limited and may be random or block.

[0028] The copolymer (P) of the component (A) can be produced, for example, as follows. A monomer composition containing various monomers for forming each constitutional unit of the formula (1a) to the formula (1c), that is, the above-mentioned PC monomer, the monomer represented by the formula (1b'), and the monomer represented by the formula (1c') can be produced by radical polymerization in the presence of a radical polymerization initiator and under an inert gas substitution or atmosphere such as nitrogen, carbon dioxide, argon, helium, etc. The polymerization method can be carried out by a known method such as bulk polymerization, suspension polymerization, emulsion polymerization, solution polymerization, etc. The purification of the copolymer (P) can be carried out by a known method such as reprecipitation method, dialysis method, ultrafiltration method, etc. Examples of the radical polymerization initiator include azo-based radical polymerization initiators, organic peroxides, persulfates, etc.

[0029] Examples of azo radical polymerization initiators include 2,2-azobis(2-diaminopropyl) dihydrochloride, 2,2-azobis(2-(5-methyl-2-imidazolin-2-yl)propane) dihydrochloride, 4,4-azobis(4-cyanovaleric acid), 2,2-azobisisobutylamide dihydrate, 2,2-azobis(2,4-dimethylvaleronitrile), and 2,2-azobisisobutyronitrile (AIBN). Examples of organic peroxides include benzoyl peroxide, diisopropyl peroxydicarbonate, t-butylperoxy-2-ethylhexanoate, lauroyl peroxide, t-butylperoxyneodecanate, and succinic acid peroxide. Examples of peroxides include ammonium persulfate, potassium persulfate, and sodium persulfate. These radical polymerization initiators can be used individually or in combination of two or more. The amount of polymerization initiator used is typically 0.001 w / w% to 10 w / w% of the monomer composition, preferably 0.01 w / w% to 5.0 w / w%.

[0030] The copolymer (P) can be produced in the presence of a solvent. Any solvent that dissolves the monomer composition without reacting with it can be used, such as alcoholic solvents, ketone solvents, ester solvents, linear or cyclic ether solvents, or nitrogen-containing solvents. Examples of alcoholic solvents include water, methanol, ethanol, n-propanol, and isopropanol. Examples of ketone solvents include acetone, methyl ethyl ketone, and diethyl ketone. Examples of ester solvents include ethyl acetate. Examples of linear or cyclic ether solvents include ethyl cellosolve and tetrahydrofuran. Examples of nitrogen-containing solvents include acetonitrile, nitromethane, and N-methylpyrrolidone. Preferably, water, alcohol, or a mixture thereof is used.

[0031] The amount of component (A) in the ophthalmic composition of the present invention is 0.01 w / w% or more and 0.5 w / w% or less. If it is less than 0.01 w / w%, the lubricity-improving effect may not be sufficiently exhibited, and if it is greater than 0.5 w / w%, sterile filtration required when manufacturing the ophthalmic composition may become difficult, or the preservative's effectiveness may be impaired. From the viewpoint of exhibiting sufficient preservative effectiveness and lubricity, the amount of component (A) is preferably 0.02 w / w% or more and 0.4 w / w% or less, more preferably 0.03 w / w% or more and 0.3 w / w% or less, and even more preferably 0.05 w / w% or more and 0.2 w / w% or less.

[0032] The component (B) contained in the ophthalmic composition of the present invention is a polyhexamethylene biguanide represented by formula (2) or a salt thereof. In formula (2), d is a number representing the repeating unit, and is an integer between 3 and 40. If the value of d is less than 3 or greater than 40, the preservative effect may not be fully realized. From the viewpoint of achieving a more sufficient preservative effect, the value of d is preferably between 10 and 18.

[0033] Examples of polyhexamethylene biguanide salts include hydrochloride, borate, acetate, gluconate, sulfonate, tartrate, or citrate. Specific examples include commercially available products such as Cosmocil CQ (registered trademark) from Arch UK Biocides, Vantcoil IB (registered trademark), and BG-1 from Sanyo Chemical Industries, Ltd. These may be used individually or in any combination of two or more types.

[0034] The amount of polyhexamethylene biguanide or its salt in component (B) of the ophthalmic composition of the present invention is 0.000001 w / w% or more and 0.0001 w / w% or less. If this is less than 0.000001 w / w%, it may not exhibit sufficient preservative efficacy, and if it is greater than 0.0001 w / w%, the improvement in preservative efficacy commensurate with the amount added may not be expected, and it may cause corneal epithelial damage. From the viewpoint of improving preservative efficacy commensurate with the amount added, the amount of component (B) is preferably 0.00001 w / w% or more and 0.00005 w / w% or less.

[0035] The ophthalmic composition of the present invention comprises at least one of (C) polyoxyethylene hydrogenated castor oil and (D) polyoxyethylene glycol monostearate. That is, the ophthalmic composition of the present invention may comprise only (C) polyoxyethylene hydrogenated castor oil (component (C)), or only (D) polyoxyethylene glycol monostearate (component (D)), or may comprise both components (C) and (D).

[0036] The number of moles of ethylene oxide added to component (C), polyoxyethylene hydrogenated castor oil, is 5 to 100, preferably 20 to 60.

[0037] The HLB of component (C), polyoxyethylene hydrogenated castor oil, is 6 to 17, preferably 10 to 15. The HLB is calculated using Griffin's formula.

[0038] (C) The polyoxyethylene hydrogenated castor oil can be any type commonly used in pharmaceuticals, for example, a product listed in the Japanese Pharmacopoeia can be used. Specific examples include commercially available products such as NOF Corporation's Yakuseki Uniox® HC-60 and Nikko Chemicals Co., Ltd.'s NIKKOL® HCO-60.

[0039] When component (C) is incorporated into the ophthalmic composition of the present invention, the amount of component (C) in the ophthalmic composition is 0.02 w / w% or more and 5.0 w / w% or less. If the amount of component (C) is less than 0.02 w / w%, the preservative effect and lubricity may decrease, and if it is greater than 5.0 w / w%, the preservative effect may decrease and the cell viability may decrease. From the viewpoint of improving preservative effect and lubricity in proportion to the amount incorporated, the amount of component (C) is preferably 0.05 w / w% or more and 3.0 w / w% or less.

[0040] The number of moles of ethylene oxide added to the polyoxyethylene glycol monostearate of component (D) is 10 to 100, preferably 20 to 45.

[0041] The HLB of component (D), polyoxyethylene glycol monostearate, is 11 to 18, preferably 14 to 18.

[0042] (D) The polyoxyethylene glycol monostearate, which is component (D), can be any type commonly used in pharmaceuticals, for example, a product listed in the Japanese Pharmacopoeia can be used. A specific example of this is polyoxyl stearate 40 from the Japanese Pharmacopoeia, manufactured by NOF Corporation.

[0043] When component (D) is incorporated into the ophthalmic composition of the present invention, the amount of component (D) in the ophthalmic composition is 0.02 w / w% or more and 5.0 w / w% or less. If the amount of component (D) is less than 0.02 w / w%, the preservative effect and lubricity may decrease, and if it is greater than 5.0 w / w%, the preservative effect may decrease and the cell viability may decrease. From the viewpoint of improving preservative effect and lubricity in proportion to the amount incorporated, the amount of component (D) is preferably 0.05 w / w% or more and 3.0 w / w% or less.

[0044] The ophthalmic composition of the present invention contains water. That is, the ophthalmic composition is prepared by mixing each of the components (A) to (D) with water.

[0045] The ophthalmic composition of the present invention may contain other components besides the components (A) to (D) described above. Examples of other components include polyhydric alcohols, cooling agents, inorganic salts, salts of organic acids, acids, bases, antioxidants, and mucin secretion promoters. Examples of polyhydric alcohols include propylene glycol, glycerin, glucose, mannitol, sorbitol, xylitol, and trehalose. Examples of cooling agents include menthol and camphor. Examples of inorganic salts include potassium chloride, sodium chloride, borax, sodium bicarbonate, sodium hydrogen phosphate, and anhydrous sodium dihydrogen phosphate. Examples of salts of organic acids include sodium citrate and sodium acetate. Examples of acids include boric acid, phosphoric acid, citric acid, sulfuric acid, acetic acid, and hydrochloric acid. Examples of bases include sodium hydroxide, potassium hydroxide, trometamol, and monoethanolamine. Examples of antioxidants include tocopherol acetate and dibutylhydroxytoluene. Examples of mucin secretion promoters include diquafosol sodium and rebamipide.

[0046] The present invention will be specifically described below with reference to examples, but the present invention is not limited to the scope of the following examples. [Evaluation] The following evaluations were made of the examples and comparative examples.

[0047] (1) Preservation efficacy test The preservation efficacy test was conducted in accordance with the section on "Preservation Efficacy Test Methods" in the "Reference Information for the 18th Revised Japanese Pharmacopoeia". Three types of bacteria were used: Escherichia coli (E.c.) (NBRC3972), Pseudomonas aeruginosa (P.a.) (NBRC13275), and Staphylococcus aureus (S.a.) (NBRC13276). Two types of fungi were used: Candida albicans (C.a.) (NBRC1594) and Aspergillus brasiliensis (A.b.) (NBRC9455). The above E.c., P.a., S. a., C. a., A. b. Redissolve BIOBALL® (manufactured by BioMérieux Japan Co., Ltd.) and add 10 per 1 mL ８ The CFU (Colony Forming Unit, the number of units capable of forming colonies) was used as the test bacterial suspension. This test bacterial suspension was added to Examples 1 to 10 and Comparative Examples 1 to 9 to a concentration of 1 v / v%, resulting in an inoculum of 10 cells per 1 mL. ６ The samples were prepared to become CFU (Cellular Fungus) and stored at 25°C. For each bacterial species, samples were taken 14 and 28 days after inoculation, cultured, and the number of viable cells was measured. Samples that did not develop colonies after 28 days were judged as good ("A"), samples that developed colonies after 28 days but the number of cells after 28 days did not increase from the number after 14 days were judged as good ("B"), and samples that increased from the number after 14 days were judged as poor ("C"). In addition, for the overall evaluation, samples that did not develop colonies in any bacterial species after 28 days were judged as good ("A"), samples that developed colonies after 28 days but were fewer than the number of cells after 14 days were judged as good ("B"), and samples that increased from the number after 14 days in at least one bacterial species were judged as poor ("C").

[0048] (2) Lubricity Evaluation Using a friction tester, the coefficient of friction was measured when acrylic plates immersed in the ophthalmic compositions of Examples 1 to 10 and Comparative Examples 1 to 9 were rubbed with a silicone probe, and the lubricity was evaluated. A coefficient of friction of 0 or more and less than 0.05 was judged as good ("A"), 0.05 or more and less than 0.1 was judged as acceptable ("B"), and 0.1 or more was judged as unacceptable ("C").

[0049] The copolymers used in the following examples or comparative examples are as follows: [Synthesis Example] (Synthesis of Copolymer P) 31.8 g of 2-methacryloyloxyethyl phosphorylcholine (MPC, manufactured by NOF Corporation), 3.6 g of stearyl methacrylate (SMA, manufactured by NOF Corporation), and 9.6 g of N,N-dimethylacrylamide (DMAA, manufactured by KJ Chemicals Co., Ltd.) were placed in a four-necked flask and dissolved in 55.0 g of ethanol, and nitrogen gas was blown in for 30 minutes. After this, the temperature was raised to 48°C, and 0.10 g of polymerization initiator (Perbutyl® ND (manufactured by NOF Corporation)) was added and the polymerization reaction was carried out for 8 hours. After the polymerization reaction, the polymerization solution was added dropwise to 3 liters of diethyl ether while stirring, the precipitated precipitate was filtered, and the mixture was vacuum dried at room temperature for 48 hours to obtain a powder. The yield was 40.2 g. Copolymer (P): Copolymer of MPC, DMAA, and SMA (Copolymerization composition ratio of MPC, DMAA, and SMA [MPC / DMAA / SMA (molar ratio) = 10 / 9 / 1], weight-average molecular weight: 100,000). The weight-average molecular weight of copolymer (P) was measured as follows.

[0050] [Measurement of Weight-Average Molecular Weight] The weight-average molecular weight was measured by gel permeation chromatography (GPC). 5 mg of the obtained copolymer (P) was dissolved in a methanol / chloroform mixture (80:20) to prepare the sample solution. The concentration of copolymer (P) in the sample solution was 0.5% by mass. The following analytical conditions were used: Column: PLgel-mixed-C Standard substance: Polyethylene glycol Detector: Differential refractometer RI-8020 (manufactured by Tosoh Corporation) Method for calculating weight-average molecular weight: Molecular weight calculation program (GPC program for SC-8020) Flow rate: 1 mL / min Injection volume: 100 μL Column oven: Constant temperature around 40°C

[0051] [Preparation of Ophthalmic Composition] (Example 1) Approximately 50 g of purified water was heated to 47.5°C, and 0.1 g of potassium chloride, 0.4 g of boric acid, 0.04 g of borax, 0.0001 g of a 20% aqueous solution of polyhexamethylene biguanide hydrochloride [Arch UK Biocides "Cosmocil CQ®"] as component (B) (0.00002 g as polyhexamethylene biguanide hydrochloride), 1.8 g of concentrated glycerin, 0.1 g of copolymer (P) as component (A), and 0.2 g of polyoxyethylene hydrogenated castor oil [NOF Corporation "Uniox® HC-60"] as component (C) were added in sequence and stirred. Then, purified water was added to make a total volume of 100 g. After this, filtration sterilization was performed to obtain a sterile ophthalmic composition. Table 1 shows the content (w / w%) of each component in the ophthalmic composition. Note that Cosmocil CQ® is a compound represented by formula (2), where d = 14.

[0052] (Examples 2-10) The types and amounts of ingredients shown in Table 1 were used, and the products were manufactured using the same procedure as in Example 1. Ingredients that are common to both the examples and comparative examples in terms of both ingredients and their amounts are listed in Table 2. The polyoxyethylene glycol monostearate used in Example 2 and other examples is "Polyoxyl 40 Stearate" manufactured by NOF Corporation.

[0053] (Comparative Examples 1-9) These were manufactured using the types and quantities of ingredients shown in Table 3, following the same procedure as in Example 1.

[0054]

[0055]

[0056]

[0057] Table 4 shows the results of the preservation efficacy test. Comparative Examples 2 and 5, which did not contain polyhexamethylene biguanide or contained it in small amounts, and Comparative Example 4, which contained a large amount of copolymer (P), did not meet the criteria. Comparative Example 8, which did not contain polyoxyethylene hydrogenated castor oil or polyoxyethylene glycol monostearate, and Comparative Examples 7 and 9, which contained them in small amounts, also did not meet the criteria. Comparative Example 6, which contained a large amount of polyoxyethylene hydrogenated castor oil, also did not meet the criteria. On the other hand, Examples 1 to 10 met the criteria for all bacteria and fungi. From the above, the ophthalmic composition of the present invention exhibits sufficient preservation efficacy.

[0058]

[0059] Table 5 shows the results of the lubricity evaluation. Comparative Examples 1 and 3, which had a low amount of copolymer (P), and Comparative Examples 8 and 9, which had a low amount of polyoxyethylene hydrogenated castor oil or polyoxyethylene glycol monostearate, showed high coefficients of friction. On the other hand, Examples 1 to 10 showed low coefficients of friction. From the above, the ophthalmic composition of the present invention has high lubricity.

[0060]

[0061] Table 6 shows the results for all test items. From these results, it was found that the ophthalmic composition of the present invention exhibits sufficient preservative effect and has high lubricity.

[0062] According to the present invention, an ophthalmic composition can be obtained that exhibits sufficient preservative effect and has high lubricity.

Claims

1. An ophthalmic composition comprising: (A) a copolymer having structural units represented by formula (1a) to formula (1c), wherein the molar ratio of each structural unit is a:b:c = 100:10 to 400:2 to 50, and the weight average molecular weight is 5,000 to 2,000,000, in an amount of 0.01 w / w% or more and 0.5 w / w% or less; (B) polyhexamethylene biguanide represented by formula (2) or a salt thereof, in an amount of 0.000001 w / w% or more and 0.0001 w / w% or less; and (C) polyoxyethylene hydrogenated castor oil in an amount of 0.02 w / w% or more and 5.0 w / w% or less and / or (D) polyoxyethylene glycol monostearate in an amount of 0.02 w / w% or more and 5.0 w / w% or less. [In formula (1a) to formula (1c), a, b, and c represent the molar ratios of the respective structural units. R １ , R ２ and R ５ each independently represent a hydrogen atom or a methyl group. R ３ and R ４ each independently represent a hydrogen atom, a methyl group, or an ethyl group. R ６ represents a monovalent hydrocarbon group having 12 to 24 carbon atoms. ] [In formula (2), d represents a number of repeating units and is an integer of 3 or more and 40 or less]

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