Ophthalmic composition

Abstract

To provide an ophthalmic composition that enables suppression of rubbing between an eyelid portion and corneal epithelial cells during blinking and, when a contact lens is worn, allows additional suppression of rubbing between the eyelid portion and the contact lens during blinking.SOLUTION: An ophthalmic composition comprising (A) at least one selected from the group consisting of chondroitin sulfate having a number average molecular weight of 15,000 to 38,000 and salts thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an ophthalmic composition containing one or more members selected from the group consisting of chondroitin sulfate and salts thereof. [Background technology]

[0002] Chondroitin sulfate and its salts are incorporated into ophthalmic compositions as ingredients that keep the eyes moist, protect the cornea, and relieve eye discomfort. With the increasing number of contact lens wearers, there has been a demand for ophthalmic compositions that are gentler on the eyes while wearing contact lenses. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2013-181020 Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention has been made in consideration of the above circumstances, and aims to provide an ophthalmic composition that suppresses rubbing between the eyelid and corneal epithelial cells due to blinking, and in addition to the above, suppresses rubbing between the eyelid and contact lens due to blinking when contact lenses are worn. [Means for solving the problem]

[0005] The inventors have focused on the friction between the eyelid and corneal epithelial cells caused by blinking, and the friction between the eyelid and contact lenses, and as a result of extensive research, have discovered that by incorporating one or more types selected from the group consisting of chondroitin sulfate and its salts having a number-average molecular weight of 15,000 to 38,000 into an ophthalmic composition, the above-mentioned friction can be particularly suppressed, the friction caused by blinking can be alleviated, and a friction-reducing effect can be obtained, which led to the present invention.

[0006] Accordingly, the present invention provides the following ophthalmic compositions. 1. (A) An ophthalmic composition comprising one or more members selected from the group consisting of chondroitin sulfate and its salts having a number average molecular weight of 15,000 to 38,000. 2. The ophthalmic composition according to 1, further comprising (B) one or more selected from the group consisting of boric acid, borax, trometamol, and edetic acid and its salts. 3. The ophthalmic composition according to 2, further comprising (C) one or more members selected from the group consisting of propylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, and hyaluronic acid and its salts. 4. The ophthalmic composition according to any one of 1 to 3, which is an eye drop for soft contact lenses. [Effects of the Invention]

[0007] According to the present invention, an ophthalmic composition can be provided that protects the cornea and pupil from friction and dryness of the eyelids and contact lenses by suppressing rubbing between the eyelids and corneal epithelial cells caused by blinking, thereby reducing damage to the cornea and pupil, eye inflammation, eye irritation, eye fatigue, and sticking and discomfort while wearing contact lenses. DETAILED DESCRIPTION OF THE INVENTION

[0008] The present invention will be described in detail below. [Component (A)] The component (A) is at least one selected from the group consisting of chondroitin sulfate and its salts having a number-average molecular weight of 15,000 to 38,000, and two or more can be used in combination. Component (A) includes chondroitin sulfate itself as well as pharmaceutically acceptable salts thereof. Specific examples include chondroitin sulfate, its alkali metal salts, alkaline earth metal salts, and the like. Examples of alkali metal salts include sodium salts and potassium salts. Examples of alkaline earth metal salts include magnesium salts and calcium salts. Among these components (A), chondroitin sulfate and alkali metal salts of chondroitin sulfate are preferred, and chondroitin sulfate and sodium chondroitin sulfate are more preferred, as they more easily provide the pharmacological actions and effects described below.

[0009] The number-average molecular weight of chondroitin sulfate and its salts is 15,000 to 38,000, with the lower limit preferably being 17,000 or more and 21,000 or more. The upper limit preferably being 33,000 or less and 28,000 or less. Preferred ranges of number-average molecular weight include combinations of the above upper and lower limits. By setting the number-average molecular weight at or above the lower limit, it becomes easier to achieve the effects of reducing friction, reducing eye inflammation, reducing eye irritation, caring for the cornea (repairing the cornea, protecting the cornea, protecting against corneal damage, and improving the corneal barrier function), alleviating eye fatigue, and inhibiting dryness of the eyes. Setting the number-average molecular weight at or below the upper limit makes it easier to achieve the effect of reducing friction and also to reduce discomfort caused by eye drops, such as stickiness.

[0010] The number average molecular weight herein can be determined, for example, by using gel permeation chromatography in which a multi-angle light scattering detector (MALS detector) and a differential refractive index detector (RI detector) are connected online. 1. Measurement conditions GPC equipment: HLC-8320GPC (Tosoh Corporation) Column: TSKgel guard column PWXL (6.0 mm I.D. x 4 cm) x 1 +GMPW XL (7.8mm I.D. x 30cm) x 2 (Tosoh Corporation) Concentration detector: RI detector polarity (+) Light scattering detector: DAWN HELEOS II (Wyatt Technology) MALS laser wavelength: 659nm Eluent: 0.1M sodium nitrate aqueous solution ·Flow rate: 0.7mL / min. Column temperature: 40℃ RI detector temperature: 40℃ ·MALS temperature: room temperature Sample concentration: 1.0 mg / mL ·Injection volume: 200μL 2. Sample pretreatment method The sample was weighed, a predetermined amount of eluent was added, and the mixture was left to dissolve overnight at room temperature, after which it was filtered through a 0.45 μm cellulose acetate cartridge filter to obtain a sample solution. 3.Analysis conditions The absolute molecular weight was calculated from the Zimm plot. The refractive index concentration increment (dn / dc) of the standard sample was calculated from the concentration and peak area ratio of the RI detector, based on the value (0.136 mL / g) of standard polyethylene oxide SE-8 manufactured by Tosoh Corporation. For other samples, the molecular weight was calculated using the value of the standard sample.

[0011] Furthermore, the weight average molecular weight and Z average molecular weight are calculated from the above test. The weight-average molecular weight (Mw) of chondroitin sulfate and its salts is not particularly limited as long as the number-average molecular weight is within the above-mentioned range, but the lower limit of the weight-average molecular weight calculated by the above-mentioned method is preferably 15,000 or more, 18,000 or more, or 22,000 or more. The upper limit is preferably 47,000 or less, 41,000 or less, or 35,000 or less. Preferred weight-average molecular weight ranges include combinations of the above-mentioned upper and lower limits. Setting the weight-average molecular weight above the lower limit makes it easier to achieve the effects of reducing friction, reducing eye inflammation, reducing eye irritation, caring for the cornea (repairing the cornea, protecting the cornea, protecting against corneal damage, and improving the corneal barrier), alleviating eye fatigue, and inhibiting dryness of the eyes. Setting the weight-average molecular weight below the upper limit makes it easier to reduce discomfort caused by eye drops, such as stickiness.

[0012] The Z-average molecular weight (Mz) of chondroitin sulfate and its salts is not particularly limited as long as the number-average molecular weight is within the above-mentioned range, but the lower limit of the Z-average molecular weight calculated by the above-mentioned method is preferably 19,000 or more, 23,000 or more, or 27,000 or more. Furthermore, the upper limit is preferably 52,000 or less, 47,000 or less, or 41,000 or less. Preferred Z-average molecular weight ranges include combinations of the above-mentioned upper and lower limits. By setting the Z-average molecular weight at or above the above-mentioned lower limit, it becomes easier to obtain the effects of reducing friction, reducing eye inflammation, reducing eye irritation, corneal care (corneal repair, corneal protection, corneal damage protection, and corneal barrier improvement), alleviating eye fatigue, and inhibiting dryness of the eyes. Setting the Z-average molecular weight at or below the upper limit makes it easier to obtain the effects of reducing friction and also to reduce discomfort caused by eye drops, such as stickiness.

[0013] The viscosity average molecular weight of chondroitin sulfate and its salts is calculated by determining the intrinsic viscosity η in accordance with the General Test Methods, Viscosity Measurement Method 1: Capillary Viscosity Method of the 18th Edition of the Japanese Pharmacopoeia (measurement conditions: solution 0.2 mol / L NaCl, temperature 25.0±0°C, Ubbelohde viscometer) and using the obtained intrinsic viscosity η according to the following formula I. Formula I: [η] = 5.8 × 10 -4 M 0.74 (where M is the viscosity average molecular weight.)

[0014] The viscosity-average molecular weight is not particularly limited as long as the number-average molecular weight is within the above-mentioned range, but the lower limit of the viscosity-average molecular weight calculated by the above-mentioned method is preferably 2,200 or more, 3,200 or more, or 4,800 or more. The upper limit is preferably 15,000 or less, 13,000 or less, or 10,000 or less. Examples of preferred viscosity-average molecular weight ranges include combinations of the above-mentioned upper and lower limits. Setting the viscosity-average molecular weight at or above the above-mentioned lower limit makes it easier to achieve the effects of reducing friction, reducing eye inflammation, reducing eye irritation, corneal care (corneal repair, corneal protection, corneal damage protection, and corneal barrier improvement), alleviating eye fatigue, and inhibiting dryness of the eyes. Setting the viscosity-average molecular weight at or below the upper limit makes it easier to achieve the effects of reducing friction and to further reduce unpleasant sensations such as stickiness caused by eye drops.

[0015] The content of component (A) in the ophthalmic composition is preferably 0.001 to 5 w / v% (mass / volume %, the same applies hereinafter), more preferably 0.01 to 2 w / v%, even more preferably 0.05 to 1 w / v%, and particularly preferably 0.1 to 0.5 w / v%. By ensuring that the content is equal to or greater than the above lower limit, the friction-reducing effect is more easily achieved, and the effects of reducing eye inflammation, reducing eye irritation, corneal care (corneal repair, corneal protection, corneal damage protection, and corneal barrier improvement), alleviating eye fatigue, and inhibiting dryness of the eyes are more easily achieved. By ensuring that the content is equal to or less than the upper limit, discomfort caused by application of eye drops, such as stickiness, is more easily alleviated.

[0016] The component (B) of the present invention is one or more selected from boric acid, borax, trometamol, and edetic acid and its salts, and two or more may be used in combination. Examples of edetate salts or salts thereof include sodium edetate (disodium ethylenediaminetetraacetate) and tetrasodium edetate (tetrasodium ethylenediaminetetraacetate), including hydrates. Examples of combinations of two or more components (B) include boric acid and trometamol, and boric acid, trometamol, and sodium edetate. From the viewpoint of preservative effectiveness, the combination of boric acid, trometamol, and sodium edetate is preferred.

[0017] The content (total amount) of component (B) in the ophthalmic composition is preferably 0.3 w / v% or more, more preferably 1.0 w / v% or more, and even more preferably 1.2 w / v% or more, and is preferably 4.2 w / v% or less, more preferably 3.5 w / v% or less, even more preferably 3.0 w / v% or less, and particularly preferably 2.5 w / v% or less. By setting the amount to the above lower limit or more, it is possible to more sufficiently increase the preservative effectiveness without containing a preservative that has corneal damaging properties, and as a result, the effects of reducing eye inflammation, reducing eye irritation, corneal care (corneal repair, corneal protection, protection against corneal damage, and improvement of the corneal barrier), eye fatigue relief, and eye dryness prevention associated with the friction reducing action of component (A) are further enhanced, and by setting the amount to the above upper limit or less, irritation is less likely to occur when instilled into the eyes, and the effects of reducing eye inflammation, reducing eye irritation, corneal care (corneal repair, corneal protection, protection against corneal damage, and improvement of the corneal barrier), eye fatigue relief, and eye dryness prevention associated with the friction reducing action of component (A) are further enhanced.

[0018] [(C) component] The ophthalmic composition of the present invention preferably further contains (C) at least one selected from propylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, and hyaluronic acid and its salts, which may be used singly or in appropriate combination of two or more.

[0019] The propylene glycol is not particularly limited, and examples thereof include propylene glycol manufactured by ADEKA Corporation.

[0020] The polyvinyl alcohol is not particularly limited, but for example, Gohsenol EG series (viscosity grade 03P (viscosity: 3.0-3.8 mm) manufactured by Mitsubishi Chemical Corporation) may be used. 2 / s), 05P (viscosity: 4.5-6.1mm 2 / s), 18P (viscosity: 15.2-20.6mm 2 / s), 22P (viscosity: 19.0-25.6mm 2 / s), 30P (viscosity: 25.5-34.5mm 2 / s), 40P (viscosity: 36.6-49.4mm 2 / s), 48P (viscosity: 41.3-55.7mm 2 / s), and among these, EG-05P is preferred. The degree of saponification is preferably 86.5 to 89.0 mol%. The viscosity and degree of saponification can be determined by the method described in the Pharmaceutical Excipients Standards 2018.

[0021] The polyvinylpyrrolidone is not particularly limited, but it is preferable to use polyvinylpyrrolidone (povidone) listed in the 18th Edition of the Japanese Pharmacopoeia. The K value is preferably 10 to 120, and the K value can be determined by the method described in the 18th Edition of the Japanese Pharmacopoeia. Examples of polyvinylpyrrolidone include those with a K value of 11 to 14 (e.g., Kollidon 12PF (manufactured by BASF Japan Ltd.)), those with a K value of 16 to 18 (e.g., Kollidon 17PF (manufactured by BASF Japan Ltd.)), those with a K value of 28 to 32 (e.g., Kollidon 30 (manufactured by BASF Japan Ltd.)), and those with a K value of 85 to 95 (e.g., Kollidon 90F (manufactured by BASF Japan Ltd.)).

[0022] There are no particular limitations on the hydroxyethyl cellulose, but it is preferable to use hydroxyethyl cellulose (hydroxyethoxyl group 30.0 to 70.0%) listed in the Pharmaceutical Excipients Standards 2018. Examples of hydroxyethyl cellulose include those having a viscosity of 300 to 600 mPa·s in a 2 w / v% aqueous solution (e.g., HEC CF-G (Sumitomo Seika Chemicals Co., Ltd.)), those having a viscosity of 5,000 to 10,000 mPa·s in a 2 w / v% aqueous solution (e.g., HEC CF-V (Sumitomo Seika Chemicals Co., Ltd.)), those having a viscosity of 10,000 to 16,000 mPa·s in a 2 w / v% aqueous solution (e.g., HEC CF-W (Sumitomo Seika Chemicals Co., Ltd.)), those having a viscosity of 1,250 to 1,750 mPa·s in a 1 w / v% aqueous solution (e.g., HEC CF-X (Sumitomo Seika Chemicals Co., Ltd.)), and those having a viscosity of 2,000 to 3,000 mPa·s in a 1 w / v% aqueous solution (e.g., HEC CF-Y (Sumitomo Seika Chemicals Co., Ltd.)).

[0023] Although there are no particular limitations on the hydroxypropyl methylcellulose, it is preferable to use hydroxypropyl methylcellulose (hypromellose) listed in the 18th Edition of the Japanese Pharmacopoeia. The degree of substitution type may be any of 2910 (methoxy group: 28.0 to 30.0, hydroxypropoxy group: 7.0 to 12.0), 2906 (methoxy group: 27.0 to 30.0, hydroxypropoxy group: 4.0 to 7.5), 2208 (methoxy group: 19.0 to 24.0, hydroxypropoxy group: 4.0 to 12.0), and 1828 (methoxy group: 16.5 to 20.0, hydroxypropoxy group: 23.0 to 32.0), with 2910, 2906, and 2208 being preferred.

[0024] Examples of hydroxypropyl methylcellulose 2910 include those having a viscosity of 40.0 to 60.0 mPa·s in a 2 w / v% aqueous solution (e.g., METLOSE 60SH50 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 3,000 to 5,600 mPa·s (e.g., METLOSE 60SH4000 (manufactured by Shin-Etsu Chemical Co., Ltd.)), and those having a viscosity of 7,500 to 14,000 mPa·s (e.g., METLOSE 60SH10000 (manufactured by Shin-Etsu Chemical Co., Ltd.)).

[0025] Examples of hydroxypropyl methylcellulose 2906 include those having a viscosity of 40.0 to 60.0 mPa·s in a 2 w / v% aqueous solution (e.g., METLOSE 65SH50 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 320 to 480 mPa·s (e.g., METLOSE 65SH400 (manufactured by Shin-Etsu Chemical Co., Ltd.)), and those having a viscosity of 3,000 to 5,600 mPa·s (e.g., METLOSE 65SH4000 (manufactured by Shin-Etsu Chemical Co., Ltd.)).

[0026] Examples of hydroxypropyl methylcellulose 2208 include those with a viscosity of 80 to 120 mPa·s in a 2 w / v% aqueous solution (e.g., METLOSE 90SH-SR100 (manufactured by Shin-Etsu Chemical Co., Ltd.)) and those with a viscosity of 3,000 to 5,600 mPa·s (e.g., METLOSE 90SH-SR4000 (manufactured by Shin-Etsu Chemical Co., Ltd.)). The viscosity of component (C) can be measured by Method 1 (at 20°C) of the Japanese Pharmacopoeia, 18th Edition, when the viscosity is less than 600 mPa·s, or by Method 2 when the viscosity is 600 mPa·s or higher.

[0027] There are no particular limitations on the methylcellulose, but it is preferable to use methylcellulose (26.0 to 33.0% methoxy groups) listed in the 18th edition of the Japanese Pharmacopoeia. Examples of methylcellulose include those having a viscosity of 3.2 to 4.8 mPa·s in a 2 w / v% aqueous solution (e.g., METLOSE SM4 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 12.0 to 18.0 mPa·s (e.g., METLOSE SM15 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 20.0 to 30.0 mPa·s (e.g., METLOSE SM25 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 80 to 120 mPa·s (e.g., METLOSE SM100 (manufactured by Shin-Etsu Chemical Co., Ltd.)), those having a viscosity of 320 to 480 mPa·s (e.g., METLOSE SM400 (manufactured by Shin-Etsu Chemical Co., Ltd.)), and those having a viscosity of 1,125 to 2,100 mPa·s (e.g., METLOSE SM1500 (manufactured by Shin-Etsu Chemical Co., Ltd.)), and a viscosity of 3,000 to 5,600 mPa·s (for example, METLOSE SM4000 (manufactured by Shin-Etsu Chemical Co., Ltd.)).

[0028] Hyaluronic acid and its salts can be obtained by extraction from chicken combs, microbial fermentation, or the like, and their origin and manufacturing method are not particularly limited. Hyaluronic acid and its salts can be used alone or in appropriate combinations of two or more. Examples include hyaluronic acid, sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, and calcium hyaluronate. Among these, sodium hyaluronate, particularly purified sodium hyaluronate listed in the 18th Revised Japanese Pharmacopoeia, is preferred. Preferred purified sodium hyaluronate is a sodium salt of hyaluronic acid with a viscosity-average molecular weight of 500,000 to 1,490,000 or 1,500,000 to 3,900,000, such as purified sodium hyaluronate (available from Seikagaku Corporation, Shiseido Co., Ltd., Kewpie Corporation, Kikkoman Biochemifa Corporation, Iwaki Pharmaceutical Co., Ltd., and Blumeji Biotechnology Inc.). The viscosity-average molecular weight can be measured by the method for measuring viscosity-average molecular weight described in "Purified Sodium Hyaluronate" listed in the 18th Edition of the Japanese Pharmacopoeia, and the viscosity-average molecular weight of hyaluronic acid or its salt in eye drops can be measured by the same method. It should be noted that multiple types of hyaluronic acid and its salt with different viscosity-average molecular weights may be used. Commercially available products include "Sodium Hyaluronate "Seikagaku"" (viscosity-average molecular weight 500,000 to 1,200,000) manufactured by Seikagaku Corporation, "Cosmetic Sodium Hyaluronate (HC)" (viscosity-average molecular weight 530,000 to 1,330,000), and "Bio Sodium Hyaluronate SZE" (viscosity-average molecular weight 1,100,000 to 1,600,000), "Bio Sodium Hyaluronate HA9N" (viscosity-average molecular weight 800,000 to 1,770,000), and "Bio Sodium Hyaluronate HA12N" manufactured by Shiseido Co., Ltd. " (viscosity average molecular weight 1.1 million to 1.6 million), "Bio-hyaluronate sodium HA20N" (viscosity average molecular weight 1.9 million to 2.7 million), "Bio-hyaluronate sodium 1% aqueous solution (MP-PE) N" (viscosity average molecular weight 1.37 million to 1.53 million), "Bio-hyaluronate sodium 1% aqueous solution (PE) N" (viscosity average molecular weight 1.37 million to 1.57 million), and "Hyaluronic acid FCH-60" (viscosity average molecular weight 500,000 to 1.57 million) manufactured by Kikkoman Biochemifa Corporation.700,000), "Hyaluronic acid FCH-80" (viscosity average molecular weight 600,000 to 1,000,000), "Hyaluronic acid FCH-120" (viscosity average molecular weight 1,000,000 to 1,400,000), "Hyaluronic acid FCH-150" (viscosity average molecular weight 1,400,000 to 1,800,000), "Hyaluronic acid FCH-151C" (viscosity average molecular weight 1,400,000 to 1,800,000), "Hyaluronic acid FCH-200" (viscosity average molecular weight 1,800,000 to 2,200,000), "Hyaluronic acid FCH-201C" (viscosity average molecular weight 1,800,000 to 2,200,000), "Hyaluronic acid FCH-80LE" (viscosity average molecular weight 600,000 to 1,200,000), "Hyaluronic acid GS-100" (viscosity average molecular weight 500,000 to 1,490,000), and "Hyaluronic acid HA-QA" (viscosity average molecular weight 600,000 to 1,200,000) and "Hyaluronic acid HA-AM" (viscosity average molecular weight 1,000,000 to 1,490,000) manufactured by Kewpie Corporation. Examples of suitable hyaluronic acid surfactants include those having a viscosity average molecular weight of 600,000 to 1,200,000, such as "Hyaluronic Acid HA-Q" (viscosity average molecular weight of 530,000 to 1,130,000), "Hyaluronic Acid M5070" (viscosity average molecular weight of 500,000 to 700,000), "Hyaluronic Acid HA-LQ" (viscosity average molecular weight of 850,000 to 1,600,000), "Hyaluronic Acid HA-LQH" (viscosity average molecular weight of 1,200,000 to 2,200,000), "Hyaluronic Acid HA-AML" (viscosity average molecular weight of 500,000 to 1,200,000), "Hyaluronic Acid HA-SHL" (viscosity average molecular weight of 1,600,000 to 2,400,000), and those manufactured by Iwaki Pharmaceutical Co., Ltd., such as "Hyaluronic Acid IW90" (viscosity average molecular weight of 800,000 to 1,170,000), "Hyaluronic Acid IW120" (viscosity average molecular weight of 1,100,000 to 1,600,000), and "Hyaluronic Acid IW200" (viscosity average molecular weight of 1,900,000 to 2,700,000).

[0029] The content (total amount) of component (C) in the ophthalmic composition is preferably 0.0001 to 5 w / v%, more preferably 0.001 to 4 w / v%, and even more preferably 0.005 to 3 w / v%. By ensuring that the content is equal to or greater than the lower limit, it becomes easier to obtain the effects of reducing friction, reducing eye inflammation, reducing eye irritation, caring for the cornea (repairing the cornea, protecting the cornea, and improving the corneal barrier), alleviating fatigue, and inhibiting dryness, while by ensuring that the content is equal to or less than the upper limit, it becomes easier to reduce the unpleasant feeling of use caused by applying eye drops, such as stickiness.

[0030] When propylene glycol is contained, the amount thereof in the ophthalmic composition is preferably 0.01 to 2 w / v%, more preferably 0.03 to 1 w / v%, even more preferably 0.04 to 0.5 w / v%, and particularly preferably 0.05 to 0.5 w / v%.

[0031] When polyvinyl alcohol is contained, the amount thereof is preferably 0.01 to 5 w / v % in the ophthalmic composition, more preferably 0.05 to 3 w / v %, and even more preferably 0.1 to 2 w / v %.

[0032] When polyvinylpyrrolidone is contained, the amount thereof is preferably 0.0001 to 5 w / v % in the ophthalmic composition, more preferably 0.001 to 2 w / v %, and even more preferably 0.01 to 0.25 w / v %.

[0033] When hydroxyethyl cellulose is contained, the amount thereof is preferably 0.0001 to 5 w / v %, more preferably 0.001 to 2 w / v %, and even more preferably 0.01 to 0.5 w / v % in the ophthalmic composition.

[0034] When hydroxypropyl methylcellulose is contained, the amount thereof is preferably 0.0001 to 5 w / v %, more preferably 0.001 to 2 w / v %, and even more preferably 0.01 to 0.5 w / v % in the ophthalmic composition.

[0035] When methylcellulose is contained, the amount thereof is preferably 0.0001 to 5 w / v % in the ophthalmic composition, more preferably 0.001 to 2 w / v %, and even more preferably 0.01 to 0.5 w / v %.

[0036] When hyaluronic acid and salts thereof are contained, the amount thereof in the ophthalmic composition is preferably 0.0001 to 5 w / v %, more preferably 0.001 to 2 w / v %, and even more preferably 0.005 to 0.5 w / v %.

[0037] [Other ingredients] The ophthalmic composition of the present invention may contain appropriate amounts of other components in addition to the above components (A) to (C), provided that the effects of the present invention are not impaired. Examples of other components include drugs other than components (A) and (C), surfactants, buffers other than component (B), isotonicity agents, pH adjusters, stabilizers, fat-soluble antioxidants, sugars, polyhydric alcohols, thickeners, cooling agents, preservatives, other inorganic compounds, and oily components. These components may be contained alone or in appropriate combinations of two or more. The amounts of the components shown below are preferred ranges when contained, and are the amounts in the ophthalmic composition.

[0038] Drugs other than component (A) and component (C) include, for example, decongestant components (vasoconstrictors) (e.g., tetrahydrozoline hydrochloride, epinephrine, epinephrine hydrochloride, methylnorepinephrine, norepinephrine, ephedrine, methylephedrine, pseudoephedrine, ephedrine hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, oxymetazoline, methoxamine, phenylpropanolamine, etilefrine, midodrine, tramazoline, synephrine, cirazoline, xylometazoline, and pharmaceutically acceptable derivatives thereof). salts thereof), anti-inflammatory agents (e.g., epsilon aminocaproic acid, allantoin, berberines, azulene sulfonic acid, azulene sulfonate lysozyme hydrochloride, zinc sulfate, zinc lactate pranoprofen, etc.), anti-inflammatory agents (e.g., glycyrrhizic acid or its salts), astringents, antihistamines (e.g., chlorpheniramine maleate, diphenhydramine hydrochloride, ketotifen fumarate, olopatadine hydrochloride, etc.), antiallergic agents (e.g., sodium cromoglycate, ashitazanolast, ibudilast, tranilast, pemirolast potassium, amlexanox, etc. ), water-soluble vitamins (pyridoxine or its salt, flavin adenine dinucleotide sodium, cyanocobalamin, panthenol, calcium pantothenate, sodium pantothenate, sodium ascorbate, etc.), fat-soluble vitamins (for example, vitamin A such as retinol palmitate, retinol acetate, retinol, retinoic acid, retinoids, etc., vitamin E such as tocopherol, tocotrienol, d-α-tocopherol acetate, dl-α-tocopherol acetate, etc.), amino acids (for example, potassium L-aspartate, L-ascorbate, etc.), magnesium aspartate, potassium and magnesium L-aspartate (equal mixture), aminoethylsulfonic acid (taurine), etc.), antibacterial ingredients (e.g., sulfonamides (sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, sulfisomidine sodium, etc.), inorganic salts (potassium chloride, calcium chloride, sodium chloride, sodium bicarbonate, sodium carbonate, dry sodium carbonate, magnesium sulfate, etc.), thickeners (glucose, etc.), local anesthetics and analgesics (chlorobutanol, oxybuprocaine hydrochloride, dibucaine hydrochloride,Examples of drugs include tetracaine hydrochloride, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothiocaine hydrochloride, lidocaine hydrochloride, neostigmine, etc. When a drug is contained, the amount can be selected based on the effective amount of each drug, but is preferably 0.001 to 5 w / v%, more preferably 0.001 to 1 w / v%, and even more preferably 0.001 to 0.1 w / v% in the ophthalmic composition.

[0039] The surfactant may be a nonionic surfactant, an amphoteric surfactant, or a cationic surfactant. The nonionic surfactant is not particularly limited as long as it is one that is used in ophthalmic compositions, and examples thereof include polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene polyoxypropylene glycol, polyethylene glycol fatty acid ester, etc. Polyoxyethylene castor oil (POE castor oil) is a compound obtained by addition polymerization of ethylene oxide (EO) to castor oil, and several types with different average moles of ethylene oxide are known. The average moles of ethylene oxide added in polyoxyethylene castor oil is not particularly limited, but examples include 3 to 60 moles. Specific examples include polyoxyethylene castor oil 3 (average moles of EO added: 3), polyoxyethylene castor oil 10 (average moles of EO added: 10), polyoxyethylene castor oil 20 (average moles of EO added: 20), polyoxyethylene castor oil 35 (average moles of EO added: 35), polyoxyethylene castor oil 40 (average moles of EO added: 40), polyoxyethylene castor oil 50 (average moles of EO added: 50), and polyoxyethylene castor oil 60 (average moles of EO added: 60).

[0040] Polyoxyethylene hydrogenated castor oil (POE hydrogenated castor oil) is a compound obtained by addition polymerization of ethylene oxide to hydrogenated castor oil, and several types are known with different average number of moles of ethylene oxide added. The average number of moles of ethylene oxide added in polyoxyethylene hydrogenated castor oil is not particularly limited, but is, for example, 5 to 100 moles. Specific examples include polyoxyethylene hydrogenated castor oil 5 (average number of moles of EO added: 5), polyoxyethylene hydrogenated castor oil 10 (average number of moles of EO added: 10), polyoxyethylene hydrogenated castor oil 20 (average number of moles of EO added: 20), polyoxyethylene hydrogenated castor oil 30 (average number of moles of EO added: 30), polyoxyethylene hydrogenated castor oil 40 (average number of moles of EO added: 40), polyoxyethylene hydrogenated castor oil 50 (average number of moles of EO added: 50), polyoxyethylene hydrogenated castor oil 60 (average number of moles of EO added: 60), polyoxyethylene hydrogenated castor oil 80 (average number of moles of EO added: 80), polyoxyethylene hydrogenated castor oil 100 (average number of moles of EO added: 100), and the like.

[0041] Specific examples of polyoxyethylene sorbitan fatty acid esters include polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monopalmitate (polysorbate 40), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan tristearate (polysorbate 65), and polyoxyethylene (20) sorbitan monooleate (polysorbate 80) (the numbers in parentheses indicate the average number of moles of polyoxyethylene added). As polyoxyethylene polyoxypropylene glycols, those listed in the Pharmaceutical Excipients Standards (2018) can be suitably used, and they can be used alone or in combination of two or more. The average degree of polymerization of ethylene oxide is preferably 3 to 200, more preferably 20 to 200, and the average degree of polymerization of propylene oxide is preferably 5 to 100, more preferably 17 to 70. While either a block copolymer or a random copolymer may be used, block copolymers are preferred. Specific examples include polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene (120) polyoxypropylene (40) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene (42) polyoxypropylene (67) glycol, polyoxyethylene (54) polyoxypropylene (39) glycol, and polyoxyethylene (20) polyoxypropylene (20) glycol. Specific examples of polyethylene glycol fatty acid esters include polyoxyl 40 stearate (average number of moles of PEG added: 40).

[0042] Examples of amphoteric surfactants include glycine-type amphoteric surfactants such as alkyldiaminoethylglycine and alkylpolyaminoethylglycine, and examples of betaine-type amphoteric surfactants include lauryldimethylaminoacetic acid betaine and imidazolium betaine. Examples of cationic surfactants include benzalkonium chloride and benzethonium chloride. When these surfactants are contained, the amount of these surfactants in the ophthalmic composition is preferably 0.01 to 0.5 w / v %, and more preferably 0.05 to 0.4 w / v %.

[0043] Examples of buffering agents other than component (B) include citric acid or its salts (e.g., sodium citrate), phosphoric acid or its salts (e.g., sodium hydrogen phosphate, sodium dihydrogen phosphate), tartaric acid or its salts (e.g., sodium tartrate), gluconic acid or its salts (e.g., sodium gluconate), acetic acid or its salts (e.g., sodium acetate), glacial acetic acid, carbonic acid or its salts (e.g., sodium carbonate, sodium bicarbonate), and various amino acids (potassium aspartate, aminoethylsulfonic acid, glutamic acid, sodium glutamate, epsilon-aminocaproic acid). These may also be hydrates. When a buffering agent is contained, its amount is preferably 0.001 to 5 w / v % of the ophthalmic composition, more preferably 0.005 to 2 w / v %, and even more preferably 0.01 to 1 w / v %.

[0044] Examples of the isotonicity agent include potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, dry sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, glycerin, propylene glycol, etc. When an isotonicity agent is contained, the amount thereof is preferably 0.00001 to 3 w / v %, more preferably 0.0001 to 2 w / v %, and even more preferably 0.005 to 1.5 w / v % in the ophthalmic composition.

[0045] Examples of pH adjusters include inorganic acids and inorganic alkali agents. Specific examples of inorganic acids include (dilute) hydrochloric acid. Examples of inorganic alkali agents include sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium bicarbonate. Other examples include monoethanolamine and diethanolamine. When a pH adjuster is contained, it is blended in an appropriate amount to achieve the pH described below.

[0046] Examples of stabilizers include cyclodextrin and monoethanolamine. Examples of fat-soluble antioxidants include dibutylhydroxytoluene and butylhydroxyanisole (BHA). When a fat-soluble antioxidant is contained, its amount in the ophthalmic composition is preferably 0.001 to 0.05 w / v%. Specifically, when dibutylhydroxytoluene is contained, its amount in the ophthalmic composition is preferably 0.001 to 0.05 w / v%, more preferably 0.003 to 0.01 w / v%. The above-mentioned preferable amount also includes the amount of dibutylhydroxytoluene (B2).

[0047] Examples of water-soluble stabilizers (antioxidants) include sulfites such as sodium sulfite, potassium sulfite, dry sodium sulfite (anhydrous sodium sulfite), sodium pyrosulfite, potassium pyrosulfite, sodium hydrogensulfite, and potassium hydrogensulfite, ascorbic acid, and sodium ascorbate.

[0048] When the ophthalmic composition of the present invention is prepared as an ophthalmic composition that can be applied to the eye while wearing soft contact lenses, the stabilizer is preferably one that has low lens adsorption and accumulation properties, and examples thereof include cyclodextrin, sulfites such as sodium sulfite, potassium sulfite, dried sodium sulfite (anhydrous sodium sulfite), sodium pyrosulfite, potassium pyrosulfite, sodium bisulfite, and potassium bisulfite, ascorbic acid, sodium ascorbate, etc. When a water-soluble stabilizer is contained, the amount thereof is preferably 0.001 to 5 w / v % of the ophthalmic composition, more preferably 0.003 to 2 w / v %, and even more preferably 0.005 to 1 w / v %.

[0049] Examples of sugars include glucose, cyclodextrin, xylitol, sorbitol, and mannitol. These may be in the d-, l-, or dl-form. Because sugars have moisturizing properties, they have the effect of increasing moisture when applied to the eye, and can also be used as isotonic agents. When sugars are contained, the amount thereof is preferably 0.001 to 5 w / v % of the ophthalmic composition, more preferably 0.003 to 2 w / v %, and even more preferably 0.005 to 1 w / v %.

[0050] Examples of polyhydric alcohols include glycerin, butylene glycol, and polyethylene glycol. Polyhydric alcohols have moisturizing properties, which increase the moisture content of the eye drops upon application, and they can also be used as isotonic agents. Glycerin and propylene glycol can also be used as solubilizers for cooling agents. When polyhydric alcohols are contained, their amount in the ophthalmic composition is preferably 0.001 to 5 w / v%, more preferably 0.003 to 2 w / v%, and even more preferably 0.005 to 1.5 w / v%.

[0051] Examples of thickeners include water-soluble polymer compounds other than component (C), such as polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, dextran, alginic acid, sodium alginate, xanthan gum, etc. When a thickener is contained, it can be contained to an extent that does not impair the feel during use, such as stickiness or blurring, and the amount thereof is preferably 0.001 to 5 w / v % of the ophthalmic composition, more preferably 0.003 to 1 w / v %, and even more preferably 0.005 to 0.5 w / v %.

[0052] Examples of refreshing agents include menthol, geraniol, cineole, linalool, anethole, eugenol, camphor, borneol, limonene, and rhubarb. They may be in the d-, l-, or dl-isomer. Other examples include essential oils such as peppermint oil, cool mint oil, spearmint oil, peppermint oil, eucalyptus oil, rose oil, fennel oil, bergamot oil, and cinnamon oil. These refreshing agents can enhance the perceived effect of sustained moisture. When a refreshing agent or essential oil is contained, the amount is preferably 0.0001 to 0.2 w / v % of the ophthalmic composition, more preferably 0.001 to 0.1 w / v %.

[0053] Examples of preservatives include chlorhexidine gluconate, chlorobutanol, benzalkonium chloride, benzethonium chloride, sorbic acid, thimerosal, phenylethyl alcohol, alkylaminoethylglycine, methyl parahydroxybenzoate, and ethyl parahydroxybenzoate. These preservatives can enhance the preservative effectiveness of the ophthalmic composition. When a preservative is contained, the amount of the preservative is preferably 0.00005 to 0.2 w / v % of the ophthalmic composition, and more preferably 0.0001 to 0.1 w / v %.

[0054] Examples of other inorganic compounds include sodium thiosulfate, titanium oxide, zinc chloride, etc. When these compounds are contained, the amount thereof in the ophthalmic composition is preferably 0.001 to 5 w / v %, more preferably 0.003 to 2 w / v %, and even more preferably 0.005 to 1 w / v %.

[0055] Examples of oily components include liquid paraffin, castor oil, soybean oil, olive oil, sesame oil, corn oil, coconut oil, almond oil, medium-chain fatty acid triglycerides, white petrolatum, wax esters, sterol esters, etc. When an oily component is contained, the amount thereof is preferably 0.001 to 1 w / v % in the ophthalmic composition.

[0056] [Ophthalmic composition] The ophthalmic composition is preferably an "aqueous ophthalmic composition." In the present invention, "aqueous ophthalmic composition" refers to an ophthalmic composition whose medium is water. The amount of water in the ophthalmic composition is preferably in the range of 90 to 99.5 w / v %.

[0057] The ophthalmic composition is preferably a liquid, and its viscosity at 20° C. is preferably 1 to 400 mPa·s, more preferably 1 to 100 mPa·s, even more preferably 1 to 60 mPa·s, and particularly preferably 1 to 30 mPa·s. The viscosity is measured using a B-type viscometer (measurement temperature: 20° C.).

[0058] The pH of the ophthalmic composition is preferably 3.5 to 8.0, more preferably 5.0 to 7.2, and even more preferably 5.5 to 7.0. The pH is measured at 25°C using a pH meter (HM-25R, DKK-Toa Corporation).

[0059] The osmotic pressure of the ophthalmic composition of the present invention is not particularly limited and can be appropriately selected depending on the intended use, etc. For example, it is usually preferable to adjust the pressure ratio to 0.5 to 5, and more preferably to 0.8 to 2. When adjusting the osmotic pressure, the adjustment method can be, for example, a method commonly used for ophthalmic compositions.

[0060] The method for preparing the ophthalmic composition of the present invention is not particularly limited, and it can be prepared in accordance with a conventional method for the dosage form and shape.

[0061] The ophthalmic composition of the present invention can be used in over-the-counter eye drops with efficacy such as relieving dry eyes, foreign body sensation in the eyes (gritty, tingly feeling), eye fatigue, blurred vision (when there is a lot of eye mucus, etc.), discomfort when wearing soft or hard contact lenses, conjunctival congestion, itchy eyes, blepharitis (sore eyelids), prevention of eye diseases (after swimming, when dust or sweat gets into the eyes, etc.), and ophthalmitis caused by ultraviolet rays or other light (snow blindness, etc.), as well as in artificial tears with efficacy such as relieving discomfort when wearing soft or hard contact lenses, supplementing tears (dry eyes), eye fatigue, blurred vision (when there is a lot of eye mucus, etc.).

[0062] The ophthalmic composition of the present invention can be suitably used as eye drops (over-the-counter eye drops, contact lens eye drops), contact lens wetting solution, contact lens removal solution, eyewash, etc., but is particularly suitable as eye drops, and more preferably as contact lens eye drops. When used as eye drops or contact lens eye drops, it is preferably administered at a dose of 10 to 60 μL (1 to 3 drops) 5 to 6 times per day, and more preferably at a dose of 30 to 50 μL (1 to 3 drops) 5 to 6 times per day. Examples of contact lenses include, but are not limited to, hard contact lenses, O2 hard contact lenses, soft contact lenses (non-ionic and ionic), silicone hydrogel contact lenses, and colored contact lenses. Soft contact lenses are not particularly limited, and can be used with all soft contact lenses classified into four FDA categories (Groups I to IV), with silicone hydrogel contact lenses falling under Group I. When the above-mentioned preservatives such as benzalkonium chloride are not contained, they are particularly suitable for use in soft contact lenses and silicone hydrogel contact lenses. Color contact lenses are used for the purpose of changing the appearance (color, pattern, or shape) of the iris or pupil, and may or may not be for vision correction, and may be for myopia, hyperopia, astigmatism, or bifocals. Color contact lenses may be in one of the four FDA classifications of soft contact lenses (Groups I to IV) mentioned above, or may be hard contact lenses. Furthermore, the lens material is not particularly limited, and color contact lenses made of any lens material are included. The colorants used to color contact lenses are not limited, but known colorants such as inorganic colorants and organic colorants can be used, and known pigments and dyes can also be used. Examples of colorants include azo colorants, phthalocyanine colorants, diketopyrrolopyrrole colorants, anthraquinone colorants, triphenodioxane colorants, violanthrone colorants, isoindoline colorants, carbazole colorants, quinoline colorants, metal oxide colorants, and carbon black, and these can be used alone or in combination of two or more.There are no limitations on the colored patterns, illustrations, designs, and colors for the purpose of eye decoration or beauty, and all patterns, illustrations, designs, and colors are included. There are also no limitations on the area of ​​the colored part or the colored part (front and back of the lens, one side, both sides, inside, etc.), and it is compatible with color contact lenses of any colored area or colored part.

[0063] [container] The container for the ophthalmic composition is a container equipped with a container body containing the ophthalmic composition and a cap. The material of the container body is not particularly limited. The container body comprises a container body (sometimes referred to as a bottle or main body) containing the ophthalmic composition and a cap. More specifically, the main body is provided with an eye dropper and a cap such as a screw type or one-touch type that seals the main body. The main body may be provided with an inner plug having an eye dropper, the eye dropper may be provided in the cap, or the cap may be attached directly to the container to seal it.

[0064] The ophthalmic composition of the present invention has a friction-reducing effect. The friction-reducing effect of the present invention is achieved by reducing the friction between the eyelid and the cornea, thereby achieving effects such as smoothing blinking, making blinking lighter, reducing friction between the eyelid and the ocular surface, and softening friction caused by blinking. Furthermore, by reducing the friction between the eyelid and a contact lens (particularly a soft contact lens), the composition can achieve effects such as alleviating foreign body sensation while wearing contact lenses, smoothing blinking, making blinking lighter, reducing friction between the eyelid and the ocular surface, and softening friction caused by blinking.

[0065] [Manufacturing method] The method for producing the ophthalmic composition of the present invention is not particularly limited. The components may be mixed by a conventional method, such as by using a pulsator, propeller blade, paddle blade, or turbine blade. The rotation speed is not particularly limited, and is preferably set to a level that does not cause vigorous foaming. The mixing temperature for the components is not particularly limited. However, when an oily component and a nonionic surfactant are contained, the temperature is preferably equal to or higher than the melting point of both the oily component and the nonionic surfactant, specifically, within the range of 40 to 95°C.

[0066] [Ophthalmology products] An ophthalmic product can be produced comprising an ophthalmic composition, a container filled with the ophthalmic composition, and an enclosure for packaging the container. When the ophthalmic composition is stored under conditions where the oxygen concentration is reduced, the stability over time of the active ingredient and water-soluble stabilizer (antioxidant) that are susceptible to oxidation is improved. As a result, components generated by oxidation that affect preservative efficacy are reduced, further improving the preservative efficacy of the ophthalmic composition. Means for storing the ophthalmic composition under conditions where the oxygen concentration is reduced include (1) injecting an inert gas into the enclosure, (2) packaging an oxygen absorber in the enclosure, (3) a container with oxygen absorbing capacity, or (4) an enclosure with oxygen absorbing capacity. It is preferable that the enclosure be capable of sealing the container.

[0067] The container is preferably a plastic container, and may be made of materials such as polyethylene, polyethylene terephthalate, polypropylene, polybutylene, polycarbonate, polyarylate, polyvinyl chloride, or a composite of these materials. Polyethylene terephthalate is particularly preferred. The oxygen permeability coefficient of the container is 10 cc / (m 2 24hr·atm) or more is preferred. The amount of ophthalmic composition in the product can be selected appropriately depending on the product and its method of use. For example, in the case of eye drops, it is preferably 2 to 20 mL, more preferably 5 to 20 mL. The capacity of the container is preferably selected appropriately depending on the amount of ophthalmic composition to be filled, and is preferably 100 to 150% of the amount of ophthalmic composition to be filled. For example, in the case of eye drops, it is preferably 2 to 30 mL. The eye drops are not particularly limited, and may be multi-dose eye drops or disposable eye drops.

[0068] The inner stopper and cap can be made of materials used for containers of known ophthalmic products. The inner stopper is preferably made of polyethylene or polypropylene with a melt flow rate of 2.0 or less, preferably 1.2 to 1.8. The cap is preferably made of polyethylene or polypropylene.

[0069] Examples of the enclosure include polyethylene, polyethylene terephthalate, polypropylene, polybutylene, polycarbonate, polyester, nylon, cellophane, polyvinyl chloride film, aluminum foil, aluminum-deposited polyvinyl alcohol-based or polyamide-based film, alumina-deposited polyethylene terephthalate, silicon oxide-deposited polyethylene terephthalate, polyvinylidene chloride-coated film or laminate film, and composite or multilayer films thereof. Among these, polyethylene terephthalate / polyethylene multilayer film and alumina-deposited polyethylene terephthalate / polyethylene multilayer film are preferred. The oxygen permeability coefficient of the enclosure is 10 cc / (m 2 ·24hr·atm) or less (i.e., 0 to 10cc / (m 2 An oxygen-impermeable enclosure of 24 hr atm is preferred.

[0070] (1) Injection of inert gas into the enclosure Examples of inert gases include nitrogen, helium, neon, and argon. Of these, nitrogen gas is preferred. The concentration of the inert gas is preferably 50% by volume or more, more preferably 80% by volume or more, and even more preferably 90% by volume or more, of the volume of the space formed between the enclosure and the plastic container. There is no particular upper limit, but it is 100% by volume or less. To achieve such a concentration, the space formed between the enclosure and the plastic container may be replaced with the inert gas.

[0071] (2) Packing oxygen absorbers inside the enclosure Specifically, AGELESS (registered trademark) (FX, SP, SS, SPE, ZP, Z-PT, Z-PT15, Z-PKC, GLS, GL-M, Z-20PK) manufactured by Mitsubishi Gas Chemical Company, Inc., PharmaKeep, Vitalon manufactured by Tokiwa Sangyo Co., Ltd., Sansoles manufactured by Hakuyo Co., Ltd., WonderKeep manufactured by Powder Tech Co., Ltd., and Sansocut manufactured by Iris Fine Products Co., Ltd. By including these oxygen absorbers in the enclosure, the oxygen concentration inside the enclosure and container can be reduced to 0.1% or less.

[0072] (3) Containers with oxygen absorption capacity Specifically, Oxyblock manufactured by Toyo Seikan Co., Ltd., Oxyvanish manufactured by Mitsubishi Gas Chemical Company, Inc., and the like can be used.

[0073] (4) Oxygen-absorbing enclosure Specifically, Oxycatch (registered trademark) ICA manufactured by Kyodo Printing Co., Ltd., Cryovac (registered trademark) OS Film manufactured by Sealed Air, Hystar O2 manufactured by Star Plastics Industries Co., Ltd., Ageless Omac manufactured by Mitsubishi Gas Chemical Company, Inc., Oxydec manufactured by Toyo Seikan Co., Ltd., etc. can be used.

[0074] The above means can be combined as appropriate, with (1), (2) and (4) being preferred, and (1)+(2), (1)+(4) and (2)+(4) being more preferred. [Example]

[0075] The present invention will be specifically described below with reference to examples and comparative examples, but the present invention is not limited to the following examples. Note that the w / v % of the composition is g / 100 mL.

[0076] [Examples and Comparative Examples] The resulting solution was mixed with an aqueous solution containing components (A), (B), and (C) to solubilize them, and the pH was adjusted to 7 with sodium hydroxide and dilute hydrochloric acid. The total volume was then adjusted with water to obtain an ophthalmic composition. The resulting ophthalmic composition was evaluated as follows.

[0077] (Test Example 1: Friction reduction effect between the cornea and eyelid model) Immortalized human corneal epithelial cells 2 x 10 4 The cells / well were seeded into a 24-well microplate (Falcon™ Cell Culture 24-well multiwell plate for cell culture) and cultured for 48 hours under conditions of 37°C and 5% CO. The 24-well microplate was attached to the moving table (bottom side) of a friction measuring instrument (mechanical surface testing platform STEP700 (manufactured by Anton Paar Japan) and nanotribometer NTR3 (manufactured by Anton Paar Japan)), and 300 μL of the ophthalmic composition of the Example or Comparative Example was seeded so that it was thoroughly distributed throughout the dish. In addition, artificial leather samples soaked in saline for 1 hour were attached to the contacts (top) of a friction measurement device (Mechanical Surface Testing Platform STEP700 (Anton Paar Japan) and Nanotribometer NTR3 (Anton Paar Japan)), and friction measurements were immediately carried out at 400 times per second for 50 seconds. The average value of the friction coefficient obtained from the measurement results 20 to 40 seconds after the start of measurement was calculated and used as the friction coefficient (μk) for each example.

[0078] (Test Example 2: Friction reduction effect between contact lenses and eyelid models) One soft contact lens (product name: Proclear 1day (Omafilcon A Group II)) was immersed in the composition of the Example or Comparative Example for 1 hour, and then attached to the moving table (bottom side) of a friction measuring device (Mechanical Surface Testing Platform STEP700 (manufactured by Anton Paar Japan) and Nanotribometer NTR3 (manufactured by Anton Paar Japan)), and 1 mL of the ophthalmic composition of the Example or Comparative Example was seeded so that it was thoroughly distributed over the soft contact lens. In addition, artificial leather samples soaked in saline for 1 hour were attached to the contacts (top) of friction measuring devices (Mechanical Surface Testing Platform STEP700 (manufactured by Anton Paar Japan) and Nanotribometer NTR3 (manufactured by Anton Paar Japan)), and friction measurements were immediately carried out for 50 seconds at 400 times per second. The average value of the friction coefficient obtained from the measurement results 20 to 40 seconds after the start of measurement was calculated and used as the friction coefficient (μk) for each example.

[0079] The friction coefficient reduction rate was calculated by calculating the rate of change in the friction coefficient of each example relative to purified water using the following formula. Friction coefficient reduction rate (%) = [(friction coefficient with saline added - friction coefficient with each addition) / friction coefficient with saline added] x 100

[0080] The results are shown together with the friction coefficient reduction rate, and are evaluated based on the friction coefficient reduction rate according to the following criteria. [Evaluation criteria for friction reduction effect] ○: Friction coefficient reduction rate (%) is 3% or more △: Friction coefficient reduction rate (%) is 0% or more but less than 3% ×: Friction coefficient reduction rate (%) is less than 0%

[0081] [Table 1]

[0082] [Table 2]

[0083] [Table 3]

[0084] [Table 4]

[0085] [Table 5]

[0086] [Table 6]

[0087] [Table 7]

[0088] [Table 8]

[0089] It has been confirmed that the ophthalmic composition of the present invention (sodium chondroitin sulfate having a number-average molecular weight of 15,000 to 38,000) reduces friction between the cornea and an eyelid model, and also reduces friction between a contact lens and an eyelid model. Furthermore, the friction-reducing effect is further improved by containing (A) sodium chondroitin sulfate having a number-average molecular weight of 15,000 to 38,000 in combination with (B) one or more selected from boric acid or borax, trometamol, and sodium edetate, and preferably by further containing (C) one or more selected from the group consisting of propylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropyl methylcellulose, methylcellulose, and hyaluronic acid and its salts. In addition, in Examples 4 to 24, even when the concentration of (A) sodium chondroitin sulfate ester having a number average molecular weight of 260,000 was changed from 0.05 w / v% to 1.2 w / v%, it was confirmed that friction between the cornea and the eyelid model and between the contact lens and the eyelid model was reduced. Furthermore, in Examples 4 to 24, even when (A) sodium chondroitin sulfate ester having a number-average molecular weight of 26,000 was changed to (A) sodium chondroitin sulfate ester having a number-average molecular weight of 21,000, or when (A) sodium chondroitin sulfate ester having a number-average molecular weight of 35,000, it was confirmed that friction between the cornea and the eyelid model and between the contact lens and the eyelid model was reduced. In Examples 46 to 52, it was confirmed that friction between the cornea and the eyelid model and between the contact lens and the eyelid model was reduced even when the concentration of (A) sodium chondroitin sulfate ester having a number average molecular weight of 260,000 was changed from 0.05 w / v% to 1.2%. Furthermore, in Examples 46 to 52, even when (A) sodium chondroitin sulfate ester having a number-average molecular weight of 26,000 was changed to (A) sodium chondroitin sulfate ester having a number-average molecular weight of 21,000, or when (A) sodium chondroitin sulfate ester having a number-average molecular weight of 35,000, it was confirmed that friction between the cornea and the eyelid model and between the contact lens and the eyelid model was reduced.

[0090] An ophthalmic composition having the following composition was prepared (pH 7). The same effects as those in the above examples were obtained.

[0091] [Table 9]

[0092] [Table 10]

[0093] [Table 11]

[0094] [Table 12]

[0095] The raw materials used in the above example are listed below. Unless otherwise specified, the amounts of each ingredient in the table are calculated as pure amounts. Additionally, the terms "Extra-Pharmacopoeia Standards," "Japanese Pharmacopoeia Standards," and "Pharmaceutical Additive Standards" below refer to raw materials that comply with the Japanese Pharmacopoeia Extra-Pharmacopoeia Standards (2002), the 18th Revised Japanese Pharmacopoeia Standards, and the Pharmaceutical Additive Standards (2018), respectively. Sodium chondroitin sulfate (number-average molecular weight: approximately 10,000): (Trade name: Sodium chondroitin sulfate "Seikagaku" for injection, Seikagaku Corporation, extra-official regulations) Sodium chondroitin sulfate (number-average molecular weight approximately 21,000): (Product name: Non-regulated sodium chondroitin sulfate, Maruha Nichiro Corporation, non-regulated) Sodium chondroitin sulfate (number-average molecular weight: approximately 26,000): (Product name: Non-regulated sodium chondroitin sulfate, Maruha Nichiro Corporation, non-regulated) Sodium chondroitin sulfate (number-average molecular weight: approximately 35,000): (Product name: Non-regulated sodium chondroitin sulfate, Maruha Nichiro Corporation, non-regulated) Sodium chondroitin sulfate (number-average molecular weight: approximately 40,000): (Trade name: Sodium chondroitin sulfate "Seikagaku" for injection, Seikagaku Corporation, extra-official regulations) Boric Acid: (Trade name: Boric Acid, Kanto Chemical Co., Ltd., Japanese Pharmacopoeia) Borax: (Trade name: Borax (powder), Kosakai Pharmaceutical Co., Ltd., Japan Pharmacopoeia) Trometamol: (trade name: 2-amino-2-hydroxymethyl-1,3-propanediol, Kanto Chemical Co., Ltd., extra-governmental regulations) Sodium edetate: (Trade name: Sodium edetate hydrate "For manufacturing use only", Fujifilm Wako Pure Chemical Industries, Ltd., Japan Pharmacopoeia) Propylene glycol: (trade name: Japanese Pharmacopoeia Propylene Glycol, ADEKA Corporation, Japan Pharmacopoeia) Polyvinyl alcohol: (trade name: Gohsenol EG-05P, Mitsubishi Chemical Corporation, Pharmaceutical Additives Regulations) Polyvinylpyrrolidone: (trade name: Povidone K90 (Kollidon 90F), BASF Japan Ltd., Japanese Pharmacopoeia) Hydroxyethyl cellulose: (trade name: HEC CF-V, Sumitomo Seika Chemicals Co., Ltd., Pharmaceutical Additives Standards) Hydroxypropyl methylcellulose: (trade name: METLOSE 60SH4000, Shin-Etsu Chemical Co., Ltd., Japanese Pharmacopoeia) Methylcellulose: (trade name: METLOSE SM4, Shin-Etsu Chemical Co., Ltd., Japanese Pharmacopoeia) Sodium hyaluronate: (trade name: Hyaluronic Acid FCH-80, manufactured by Kikkoman Biochemifa Corporation) Dilute hydrochloric acid (trade name: Dilute Hydrochloric Acid, Kosakai Pharmaceutical Co., Ltd., Japan Pharmacopoeia) Sodium hydroxide (trade name: Sodium Hydroxide, Kosakai Pharmaceutical Co., Ltd., Japan Pharmacopoeia) Purified water: (Product name: Japanese Pharmacopoeia Purified Water (Distilled Water), manufactured by Kyoei Pharmaceutical Co., Ltd.)

Claims

1. (A) An ophthalmic composition comprising one or more members selected from the group consisting of chondroitin sulfates and salts thereof having a number average molecular weight of 15,000 to 38,000.

2. The ophthalmic composition according to claim 1, further comprising (B) one or more selected from the group consisting of boric acid, borax, trometamol, and edetic acid and its salts.

3. The ophthalmic composition according to claim 2, further comprising (C) one or more selected from the group consisting of propylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropyl methylcellulose, methylcellulose, and hyaluronic acid and its salts.

4. The ophthalmic composition according to any one of claims 1 to 3, which is an eye drop for soft contact lenses.

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