Ophthalmic composition

Abstract

To provide an ophthalmic composition that comprises chondroitin sulfate or a salt thereof in high concentrations and ensures an aseptic property, while it can be charged into a container in a more accurate fluid volume.SOLUTION: An ophthalmic composition contains (A) at least one selected from the group consisting of chondroitin sulfate and a salt thereof and (B) at least one selected from the group consisting of (B-1) zinc chloride and (B-2) chelator and contains no benzalkonium chloride, where, the content of (A) component is 0.7 w / v% or more based on the total amount of the ophthalmic composition.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to ophthalmic compositions. [Background technology]

[0002] When manufacturing pharmaceuticals such as eye drops and eyewashes, it is necessary to fill containers with an accurate amount of medicinal liquid. Typically, in the filling process, the medicinal liquid is filled into the container through a filling needle, and filling an accurate amount of medicinal liquid can be achieved by accurately controlling the amount of liquid that drips from the filling needle.

[0003] On the other hand, chondroitin sulfate or a salt thereof is incorporated into ophthalmic compositions for the purposes of promoting energy metabolism, relieving eye fatigue by promoting metabolism and cellular respiration, and replenishing tear components (e.g., Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-148791 Summary of the Invention [Problem to be solved by the invention]

[0005] The present inventors have discovered a new problem: when benzalkonium chloride, which is used as a preservative, is added to an ophthalmic composition containing a high concentration (e.g., 1.0 w / v % or more) of chondroitin sulfate or a salt thereof, the liquid does not drain well from the filling needle, making it difficult to control the amount of droplets, and making it impossible to fill an accurate amount of the ophthalmic composition into a container.

[0006] An object of the present invention is to provide an ophthalmic composition that contains chondroitin sulfate or a salt thereof at a high concentration, has antiseptic properties, and can be filled into a container in a more accurate amount. [Means for solving the problem]

[0007] The present inventors have found that by blending zinc chloride or edetic acid or a salt thereof with an ophthalmic composition containing a high concentration of at least one selected from the group consisting of chondroitin sulfate and its salts, it is possible to ensure antiseptic properties while improving drainage from a filling needle and filling a container with a more accurate amount of the ophthalmic composition. The present invention is based on this finding and provides the following inventions.

[0008] [1] An ophthalmic composition comprising (A) at least one selected from the group consisting of chondroitin sulfate and its salts, and (B) at least one selected from the group consisting of (B-1) zinc chloride and (B-2) a chelating agent, and not containing benzalkonium chloride, wherein the content of component (A) is 0.7 w / v% or more based on the total amount of the ophthalmic composition. [2] The ophthalmic composition according to [1], wherein the content of component (A) is 1.0 w / v% or more based on the total amount of the ophthalmic composition. [3] The ophthalmic composition according to [1], wherein the content of component (A) is 3.0 w / v% or more based on the total amount of the ophthalmic composition. [4] The ophthalmic composition according to any one of [1] to [3], wherein the component (B-2) is at least one selected from the group consisting of edetic acid and salts thereof. [5] The ophthalmic composition according to any one of [1] to [4], wherein the content of component (B-2) is 0.05 w / v % or more based on the total amount of the ophthalmic composition. [6] The ophthalmic composition according to any one of [1] to [5], further comprising (C) a buffering agent. [7] The ophthalmic composition according to any one of [1] to [6], which does not further contain any preservative other than benzalkonium chloride. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide an ophthalmic composition that contains chondroitin sulfate or a salt thereof at a high concentration, and that can be filled into a container in a more accurate amount while ensuring preservative properties. The ophthalmic composition of the present invention is preferable because it does not contain a preservative such as benzalkonium chloride. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited to the following embodiments.

[0011] In this specification, unless otherwise specified, the unit of content "%" means "w / v%" and is synonymous with "g / 100 mL".

[0012] [1. Ophthalmic composition] The ophthalmic composition according to this embodiment contains at least one selected from the group consisting of chondroitin sulfate and salts thereof (also simply referred to as "component (A)").

[0013] [Component (A)] The ophthalmic composition according to this embodiment contains (A) at least one selected from the group consisting of chondroitin sulfate and salts thereof (also simply referred to as "component (A)").

[0014] Chondroitin sulfate and its salts, which are component (A), are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable. The molecular weight of chondroitin sulfate and its salts is not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable, but typically, those with a weight-average molecular weight of about 1,000 to 100,000, preferably about 5,000 to 50,000, and more preferably about 10,000 to 40,000 can be used.

[0015] Examples of salts of chondroitin sulfate include alkali metal salts and alkaline earth metal salts. Examples of alkali metal salts include sodium salt and potassium salt. Examples of alkaline earth metal salts include magnesium salt and calcium salt.

[0016] As chondroitin sulfate and salts thereof, chondroitin sulfate and alkali metal salts of chondroitin sulfate are preferred, chondroitin sulfate and sodium chondroitin sulfate are more preferred, and sodium chondroitin sulfate is even more preferred.

[0017] Chondroitin sulfate and salts thereof may be commercially available. One type of chondroitin sulfate and salts thereof may be used alone, or two or more types may be used in combination.

[0018] The content of component (A) in the ophthalmic composition according to this embodiment is 0.7 w / v% or more, based on the total amount of the ophthalmic composition. The lower limit of the content of component (A) is not particularly limited as long as it is 0.7 w / v% or more, and is set appropriately depending on the type of component (A), the types and amounts of other components added, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly achieving the effects of the present invention, the lower limit of the content of component (A) is, for example, preferably 0.7 w / v% or more, more preferably 1.0 w / v% or more, even more preferably 2.0 w / v% or more, even more preferably 2.5 w / v% or more, and particularly preferably 3.0 w / v% or more. The upper limit of the content of component (A) is not particularly limited, and is set appropriately depending on the type of component (A), the types and amounts of other components added, the intended use and formulation of the ophthalmic composition, etc. The upper limit of the content of component (A) is, for example, preferably 5.0 w / v% or less, more preferably 4.0 w / v% or less, even more preferably 3.5 w / v% or less, and even more preferably 3.0 w / v% or less, from the viewpoint of more pronounced effects of the present invention and the feeling when used. The content of component (A) in the ophthalmic composition according to this embodiment may be, for example, 0.7 to 5.0 w / v%, 0.7 to 4.0 w / v%, 0.7 to 3.5 w / v%, 0.7 to 3.0 w / v%, 0.7 to 1.5 w / v%, 0.7 to 1.0 w / v%, 1.0 to 5.0 w / v%, 1.0 to 4.0 w / v%, 1.0 to 3.5 w / v%, 1.0 to 3.0 w / v%, 2.0 to 5.0 w / v%, 2.0 to 4.0 w / v%, 2.0 to 3.5 w / v%, 2.0 to 3.0 w / v%, 2.5 to 5.0 w / v%, 2.5 to 4.0 w / v%, 2.5 to 3.5 w / v%, or 2.5 to 3.0 w / v%, based on the total amount of the ophthalmic composition. In another aspect, the content of component (A) in the ophthalmic composition of this embodiment may be, for example, 1.0 w / v%, 2.0 w / v%, or 3.0 w / v%, based on the total amount of the ophthalmic composition.

[0019] [(B) component] The ophthalmic composition according to this embodiment further contains, in addition to the component (A), at least one selected from the group consisting of (B)(B-1) zinc chloride (also simply referred to as "component (B-1)") and (B-2) a chelating agent (also simply referred to as "component (B-2)"). (Hereinafter, components (B-1) and (B-2) will be collectively referred to as "component (B)".) One component (B) may be used alone, or two or more components may be used in combination.

[0020] [(B-1) component] There are no particular limitations on the zinc chloride used as component (B-1), so long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable.

[0021] The content of component (B-1) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types and contents of other blended components, the intended use of the ophthalmic composition, the formulation form, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (B-1) is, for example, preferably 0.00001 to 0.05 w / v%, more preferably 0.00005 to 0.02 w / v%, even more preferably 0.0001 to 0.01 w / v%, and even more preferably 0.0005 to 0.005 w / v%, based on the total amount of the ophthalmic composition.

[0022] The content ratio of component (B-1) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (A), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B-1) relative to component (A) is, for example, preferably 0.000003 to 0.05 parts by mass, more preferably 0.000017 to 0.02 parts by mass, even more preferably 0.00003 to 0.01 parts by mass, and even more preferably 0.00017 to 0.005 parts by mass, of the total content of component (B-1) relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0023] [(B-2) component] The chelating agent serving as component (B-2) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable, and examples thereof include edetic acid and its salts, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), and diethylenetriaminepentaacetic acid (DTPA), and among these, edetic acid or its salts are preferably used.

[0024] Edetic acid, also known as ethylenediaminetetraacetic acid (EDTA), is 10 H 16 It is a known compound represented by the formula N2O8.

[0025] Examples of salts of edetic acid include alkali metal salts such as sodium edetate, disodium edetate, and tetrasodium edetate, and among these, disodium edetate is preferably used.

[0026] The content of component (B-2) in the ophthalmic composition according to this embodiment is not particularly limited and is appropriately determined depending on the type of component (B-2), the types and contents of other components, the intended use of the ophthalmic composition, the formulation, etc. From the viewpoint of further enhancing the preservative effect, the content of component (B-2) is, for example, preferably 0.01 w / v% or more, more preferably 0.03 w / v% or more, even more preferably 0.05 w / v% or more, even more preferably 0.07 w / v% or more, and particularly preferably 0.09 w / v% or more, based on the total amount of the ophthalmic composition. Furthermore, from the viewpoint of more significantly achieving the effects of the present invention, the content of component (B-2) is, for example, preferably 10 w / v% or less, more preferably 5 w / v% or less, even more preferably 3 w / v% or less, even more preferably 1 w / v% or less, and particularly preferably 0.5 w / v% or less, based on the total amount of the ophthalmic composition. Furthermore, the content of component (B-2) in the ophthalmic composition according to this embodiment may be, for example, 0.01 to 10 w / v%, 0.03 to 5 w / v%, 0.05 to 3 w / v%, 0.07 to 1 w / v%, or 0.09 to 0.5 w / v%, based on the total amount of the ophthalmic composition.

[0027] The content ratio of component (B-2) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B-2), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B-2) relative to component (A) is, for example, preferably 0.003 to 10 parts by mass, more preferably 0.01 to 5 parts by mass, even more preferably 0.017 to 3 parts by mass, even more preferably 0.023 to 1 part by mass, and particularly preferably 0.03 to 0.5 parts by mass, of the total content of component (B-2) relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0028] [(C) component] The ophthalmic composition according to this embodiment may further contain a buffer (C) (also simply referred to as "component (C)"). When the ophthalmic composition further contains component (C), the effects of the present invention are more pronounced.

[0029] The buffering agent is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable.

[0030] Examples of the buffer include inorganic buffers, which are buffers derived from inorganic acids, and organic buffers, which are buffers derived from organic acids or organic bases.

[0031] Examples of inorganic buffers include borate buffers, phosphate buffers, and carbonate buffers. Examples of borate buffers include boric acid or its salts (alkali metal borates, alkaline earth metal borates, etc.). Examples of phosphate buffers include phosphoric acid or its salts (alkali metal phosphates, alkaline earth metal phosphates, etc.). Examples of carbonate buffers include carbonic acid or its salts (alkali metal carbonates, alkaline earth metal carbonates, etc.). Furthermore, hydrates of borate, phosphate, or carbonate may be used as borate buffers, phosphate buffers, or carbonate buffers. More specific examples of borate buffers include boric acid or salts thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); phosphate buffers include phosphoric acid or salts thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); and carbonate buffers include carbonic acid or salts thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.).

[0032] Examples of organic buffers include citrate buffers, acetate buffers, lactate buffers, succinate buffers, Tris buffers, and AMPD buffers. Examples of citrate buffers include citric acid or salts thereof (such as alkali metal citrates and alkaline earth metal citrates). Examples of acetate buffers include acetic acid or salts thereof (such as alkali metal acetates and alkaline earth metal acetates). Examples of lactate buffers include lactic acid or salts thereof (such as alkali metal lactates and alkaline earth metal lactates). Examples of succinate buffers include succinic acid or salts thereof (such as alkali metal succinates). Furthermore, hydrates of citrate, acetate, lactate, or succinate may be used as citrate buffers, acetate buffers, lactate buffers, or succinate buffers. More specific examples of citrate buffers include citric acid or its salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetate buffers include acetic acid or its salts (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.); lactate buffers include lactic acid or its salts (sodium lactate, potassium lactate, calcium lactate, etc.); and succinate buffers include succinic acid or its salts (monosodium succinate, disodium succinate, etc.). Examples of Tris buffers include trometamol or its salts (trometamol hydrochloride, etc.). Examples of AMPD buffers include 2-amino-2-methyl-1,3-propanediol or its salts.

[0033] As the buffer, boric acid buffer (e.g., a combination of boric acid and borax), phosphate buffer (e.g., a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), and Tris buffer (e.g., trometamol) are preferred, with boric acid buffer being more preferred, boric acid and its salts being even more preferred, and a combination of boric acid and borax being even more preferred.

[0034] The buffering agent may be a commercially available product. One type of buffering agent may be used alone, or two or more types may be used in combination.

[0035] The content of component (C) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (C), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (C) is, for example, preferably 0.01 to 10 w / v%, more preferably 0.05 to 5 w / v%, and even more preferably 0.1 to 3 w / v%, based on the total amount of the ophthalmic composition.

[0036] The content ratio of component (C) to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (C), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (C) to component (A) is, for example, preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and even more preferably 0.5 to 3 parts by mass, of the total content of component (C) per 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0037] [(D) component] The ophthalmic composition according to this embodiment may further contain (D) an isotonic agent (also simply referred to as "component (D)"). When the ophthalmic composition further contains component (D), the effects of the present invention are more pronounced. There are no particular limitations on component (D), so long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable.

[0038] The tonicity adjusting agent, which is the component (D), includes, for example, ionic tonicity adjusting agents and non-ionic tonicity adjusting agents.

[0039] Examples of ionic tonicity agents include inorganic salts such as calcium chloride, magnesium chloride, sodium chloride, potassium chloride, ammonium chloride, calcium sulfate, magnesium sulfate, sodium sulfate, and potassium sulfate, as well as monoethanolamine, diethanolamine, and triethanolamine. Among the ionic tonicity agents, sodium chloride and monoethanolamine are preferred from the viewpoint of more significantly exhibiting the effects of the present invention.

[0040] Examples of nonionic tonicity agents include alcohols such as glycerin, propylene glycol, polyethylene glycol (400, 4000, 6000, etc.), glucose, sorbitol, mannitol, xylitol, and trehalose. Among nonionic tonicity agents, mannitol is preferred from the viewpoint of more significantly exhibiting the effects of the present invention and preventing the preparation from becoming sticky.

[0041] The tonicity adjusting agent may be a commercially available one. One type of tonicity adjusting agent may be used alone, or two or more types may be used in combination.

[0042] The total content of component (D) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (D), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (D) is, for example, preferably 0.0001 to 10 w / v%, more preferably 0.0005 to 7 w / v%, even more preferably 0.001 to 6 w / v%, even more preferably 0.005 to 5 w / v%, particularly preferably 0.005 to 4 w / v%, more particularly preferably 0.005 to 3 w / v%, even more particularly preferably 0.01 to 2 w / v%, even more particularly preferably 0.01 to 1.5 w / v%, and most preferably 0.05 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0043] The content ratio of component (D) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (D), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content ratio of component (D) relative to component (A) is, for example, preferably 0.00003 to 10 parts by mass, more preferably 0.00017 to 7 parts by mass, even more preferably 0.0003 to 6 parts by mass, even more preferably 0.0017 to 5 parts by mass, particularly preferably 0.0017 to 4 parts by mass, more particularly preferably 0.0017 to 3 parts by mass, even more particularly preferably 0.003 to 2 parts by mass, even more particularly preferably 0.003 to 1.5 parts by mass, and most preferably 0.016 to 1 part by mass, of the total content of component (D) contained in the ophthalmic composition according to this embodiment.

[0044] The ophthalmic composition according to this embodiment does not contain benzalkonium chloride, which can suppress side effects such as inflammation of the cornea and conjunctiva and allergies caused by benzalkonium chloride, and can more significantly exhibit the effects of the present invention.

[0045] The pH of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable range. The pH of the ophthalmic composition according to this embodiment may be, for example, 4.0 to 9.5, preferably 4.0 to 9.0, more preferably 4.5 to 9.0, even more preferably 4.5 to 8.5, even more preferably 5.0 to 8.5, particularly preferably 5.5 to 8.0, and particularly more preferably 6.0 to 7.8.

[0046] The ophthalmic composition according to this embodiment can be adjusted to an osmotic pressure ratio within a biologically acceptable range, as needed. The appropriate osmotic pressure ratio varies depending on the application site, dosage form, etc.; however, to more significantly exhibit the effects of the present invention, it is preferably 0.05 to 6, more preferably 0.4 to 5, even more preferably 0.6 to 3, and even more preferably 0.8 to 2. The osmotic pressure ratio may also be 0.3 to 4, 0.5 to 3, or 0.7 to 1.4. The osmotic pressure can be adjusted using inorganic salts, polyhydric alcohols, etc., by methods known in the art. The osmotic pressure ratio is defined as the ratio of the osmotic pressure of the sample to 286 mOsm (the osmotic pressure of a 0.9 w / v% sodium chloride aqueous solution) according to the 17th Edition of the Japanese Pharmacopoeia. The osmotic pressure is measured using the osmotic pressure measurement method (freezing-point depression method) described in the Japanese Pharmacopoeia. The standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution) can be prepared by drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500-650°C for 40-50 minutes, allowing it to cool in a desiccator (silica gel), accurately weighing 0.900 g of the solution, and dissolving it in purified water to make exactly 100 mL; alternatively, a commercially available standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution) can be used.

[0047] The viscosity of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable range. For example, the viscosity of the ophthalmic composition according to this embodiment, as measured at 20°C using a rotational viscometer (TV-20 viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34' x R24), is preferably 0.1 to 10,000 mPa·s, more preferably 1 to 3,000 mPa·s, even more preferably 1 to 1,000 mPa·s, even more preferably 1 to 100 mPa·s, particularly preferably 1 to 50 mPa·s, particularly more preferably 1 to 10 mPa·s, and even more preferably 1.3 to 5 mPa·s. Alternatively, the viscosity may be 1 to 5 mPa·s, 1 to 4 mPa·s, or 1 to 3 mPa·s.

[0048] The ophthalmic composition according to this embodiment may contain, in addition to the above-mentioned components, a combination of various pharmacologically active components and physiologically active components in appropriate amounts, as long as the effects of the present invention are not impaired. The components are not particularly limited, and examples thereof include active ingredients in ophthalmic drugs listed in the 2012 edition of the OTC Drug Manufacturing and Marketing Approval Standards (supervised by the Japan Society of Regulatory Science). Specific examples of components used in ophthalmic drugs include the following: Antiallergic agents: for example, sodium cromoglycate, tranilast, pemirolast potassium, etc. Antihistamines: for example, diphenhydramine hydrochloride, iproheptine, chlorpheniramine maleate, levocabastine hydrochloride, ketotifen fumarate, pemirolast potassium, olopatadine hydrochloride, etc. Anti-inflammatory agents: for example, methyl salicylate, glycol salicylate, allantoin, tranexamic acid, lysozyme, lysozyme chloride, indomethacin, pranoprofen, ibuprofen, ibuprofen piconol, ketoprofen, felbinac, bendazac, piroxicam, bufexamac, butyl flufenamate, epsilon-aminocaproic acid, berberine chloride, berberine sulfate, sodium azulene sulfonate, etc. Steroids: for example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc. Decongestants: for example, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, etc. Ocular muscle regulating agents: For example, cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically neostigmine methylsulfate, tropicamide, helenien, atropine sulfate, etc. Vitamins: for example, retinol acetate, retinol palmitate, tocopherol acetate, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, ascorbic acid, sodium ascorbate, etc. Amino acids: for example, glutamic acid, aspartic acid, arginine, glycine, aminoethylsulfonic acid (taurine), trimethylglycine and salts thereof. Astringents: for example, zinc oxide, zinc lactate, zinc sulfate, etc. Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidine and their salts.

[0049] The ophthalmic composition according to this embodiment may contain one or more additives selected appropriately in a conventional manner depending on the intended use and formulation, as long as the effects of the present invention are not impaired. Examples of such additives include those listed in the Pharmaceutical Additives Dictionary 2007 (edited by the Japan Pharmaceutical Additives Association). Representative additives include the following: Carrier: For example, an aqueous solvent such as water or aqueous ethanol. Bases: for example, octyldodecanol, titanium oxide, potassium bromide, plastibase, etc. pH adjusters: for example, hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, diisopropanolamine, etc. Stabilizers: for example, sodium formaldehyde sulfoxylate (Rongalit), sodium hydrogen sulfite, sodium pyrosulfite, aluminum monostearate, glycerin monostearate, cyclodextrin, monoethanolamine, dibutylhydroxytoluene, etc. Thickeners other than component (A): for example, cellulose-based polymer compounds (e.g., methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, etc.), polyvinyl-based polymer compounds (e.g., polyvinylpyrrolidone, polyvinyl alcohol, etc.), carboxyvinyl polymers, guar gum, hydroxypropyl guar gum, gum arabic, karaya gum, xanthan gum, agar, alginic acid and its salts (e.g., sodium salt), mucopolysaccharides (e.g., heparinoids, heparin, heparin, heparin sulfate, heparan sulfate, heparinoid, hyaluronic acid and its salts (e.g., sodium salt)), starch, chitin and its derivatives, chitosan and its derivatives, carrageenan, etc. Sugars: for example, glucose, cyclodextrin, etc. Anionic surfactants: for example, polyoxyethylene alkyl ether phosphates, polyoxyethylene alkyl ether sulfates, alkylbenzenesulfonates, alkyl sulfates, N-acyltaurine salts, etc. Amphoteric surfactants: for example, lauryl dimethylaminoacetic acid betaine. Preservatives other than benzalkonium chloride: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, chlorhexidine and salts thereof (specifically, chlorhexidine hydrochloride, chlorhexidine acetate, chlorhexidine gluconate, etc.), dibutylhydroxytoluene, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexanide hydrochloride (polyhexamethylene biguanide), alexidine hydrochloride, etc.), GLOQIL (trade name manufactured by Rhodia), etc. From the viewpoint of further enhancing the effects of the present invention, the ophthalmic composition according to this embodiment preferably does not contain, in addition to benzalkonium chloride, any preservatives other than benzalkonium chloride.

[0050] From the viewpoint of being able to significantly exhibit the effects of the present invention, the ophthalmic composition according to this embodiment preferably does not contain at least one selected from the group consisting of sodium cromoglycate, phenylephrine hydrochloride, pranoprofen, allantoin, chlorpheniramine maleate, naphazoline, tetrahydrozoline hydrochloride, neostigmine methylsulfate, potassium sorbate, and chlorhexidine gluconate.

[0051] The ophthalmic composition according to this embodiment may be an aqueous composition (mainly containing an aqueous or hydrophilic base or carrier) or an oil-based composition (mainly containing an oil-based or hydrophobic base or carrier). When the ophthalmic composition is an aqueous composition, the water content is, for example, preferably 50% by weight or more, more preferably 75% by weight or more, even more preferably 80% by weight or more, even more preferably 85% by weight or more, and particularly preferably 90% by weight or more, based on the total weight of the ophthalmic composition. When the ophthalmic composition is an aqueous composition, the water content is, for example, preferably less than 100% by weight, more preferably 99.5% by weight or less, even more preferably 99.2% by weight or less, even more preferably 99.0% by weight or less, particularly preferably 97.0% by weight or less, and most preferably 96.5% by weight or less, based on the total weight of the ophthalmic composition. When the ophthalmic composition is an oily composition, the water content is, for example, preferably less than 50% by weight, more preferably 30% by weight or less, and even more preferably 20% by weight or less, based on the total weight of the ophthalmic composition. The ophthalmic composition according to this embodiment is preferably an aqueous composition.

[0052] The water used in the ophthalmic composition according to this embodiment may be any water that is medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable. Examples of such water include distilled water, tap water, purified water, sterile purified water, water for injection, and distilled water for injection. These definitions are based on the Japanese Pharmacopoeia, 17th Edition.

[0053] The ophthalmic composition according to the present embodiment can be prepared, for example, by adding and mixing the components (A), (B), and, if necessary, other components to a desired content. Specifically, the composition can be prepared, for example, by dissolving or suspending the components in purified water, adjusting the pH and osmotic pressure to a predetermined value, and sterilizing the mixture by filtration or the like.

[0054] The ophthalmic composition according to the present embodiment can be in various dosage forms depending on the purpose, such as a liquid, a gel, a semi-solid (ointment, etc.), etc. Among these, a liquid is preferred, and an aqueous liquid is more preferred.

[0055] The ophthalmic composition according to this embodiment can be used, for example, as eye drops (also referred to as eye drops or eye drops; eye drops include artificial tears and eye drops that can be applied to the eyes while wearing contact lenses), eyewash (also referred to as eyewash or eyewash; eyewashes include eyewashes that can be applied to the eyes while wearing contact lenses), or a contact lens composition (contact lens wetting solution, contact lens care composition (contact lens disinfectant, contact lens preservative, contact lens cleaner, contact lens cleaning and preservative), contact lens wetting solution that can be used both as a contact lens wetting solution and as an eye drop while wearing contact lenses, etc.). Suitable examples of the ophthalmic composition according to this embodiment include eye drops, eyewash, and contact lens compositions, more suitable examples include eye drops that can be applied to the eyes while wearing contact lenses, eyewashes that can be applied to the eyes while wearing contact lenses, contact lens wetting solution, and contact lens wetting solution, and even more suitable examples include eye drops that can be applied to the eyes while wearing contact lenses. The term "contact lenses" includes hard contact lenses and soft contact lenses (including both ionic and non-ionic contact lenses, and both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses). In this specification, "soft contact lenses" refers to a classification of soft contact lenses based on the "Classification Method for Soft Contact Lenses" stipulated in the Notification of the Director of the Evaluation and Licensing Division, Pharmaceutical and Medical Safety Bureau, Ministry of Health, Labour and Welfare (then the Ministry of Health and Welfare), dated March 31, 1999, entitled "Handling of Documents to be Attached to Applications for Approval to Manufacture (Import) Soft Contact Lenses and Soft Contact Lens Disinfectants," No. 645. Here, soft contact lenses are classified based on criteria such as water content and the mole percentage of anionic monomers. For example, soft contact lenses belonging to Group IV have common properties of having a water content of 50% or more and having 1% or more mole percentage of anionic monomers among the constituent monomers of the raw material polymer. This classification follows the classification method for soft contact lenses established by the FDA (U.S. Food and Drug Administration).

[0056] When the ophthalmic composition according to this embodiment is in the form of eye drops, the effects of the present invention can be more significantly exhibited, so the ophthalmic composition is preferably an eye drop that can be instilled while wearing contact lenses, more preferably an eye drop that can be instilled while wearing soft contact lenses (eye drops for soft contact lenses), and even more preferably an ophthalmic composition for soft contact lenses of Group IV in the FDA contact lens classification. When the ophthalmic composition according to this embodiment is in the form of eye drops, the dosage and administration method are not particularly limited as long as they are effective and have few side effects. For example, for adults (15 years of age or older) and children aged 7 years of age or older, 1 to 2 drops at a time, 2 to 4 times a day, or 4 times a day, or 1 to 2 drops, 1 to 3 drops, or 2 to 3 drops at a time, 5 to 6 times a day, can be exemplified.

[0057] The ophthalmic composition according to this embodiment is preferably an artificial tear, since this allows the effects of the present invention to be more pronounced. When the ophthalmic composition according to this embodiment is an artificial tear, it is preferable that the ophthalmic composition does not contain any of an anti-inflammatory agent, an antiallergic agent, an antihistamine, a steroid, a decongestant, an eye muscle regulating agent, a vitamin, an astringent, sulfamethoxazole, sulfisoxazole, or sulfisomidine.

[0058] The ophthalmic composition according to this embodiment is provided in any container. The container for containing the ophthalmic composition according to this embodiment is not particularly limited and may be made of, for example, glass or plastic. Plastic is preferred. Examples of plastic include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, copolymers of monomers constituting these, and mixtures of two or more of these. Polypropylene, polyethylene, and polyethylene terephthalate are preferred, and polyethylene terephthalate is more preferred. Furthermore, the container for containing the ophthalmic composition according to this embodiment may be a transparent container that allows the interior of the container to be seen, or an opaque container that makes it difficult to see the interior of the container. A transparent container is preferred. Here, the term "transparent container" includes both colorless transparent containers and colored transparent containers.

[0059] A nozzle may be attached to the container that contains the ophthalmic composition according to this embodiment. The material of the nozzle is not particularly limited and may be, for example, glass or plastic. Plastic is preferred. Examples of plastic include polybutylene terephthalate, polyethylene, polypropylene, polyethylene naphthalate, copolymers of monomers constituting these, and mixtures of two or more of these. From the viewpoint of further enhancing the effects of the present invention, polypropylene, polyethylene, polyethylene terephthalate, and polyethylene naphthalate are preferred as the material of the nozzle, with polyethylene being more preferred.

[0060] The container for holding the ophthalmic composition of this embodiment may be a multi-dose type that holds an amount for multiple uses, or a unit-dose type that holds an amount for a single use, but it is preferable that it be a multi-dose type as this allows the effects of the present invention to be more pronounced. [Example]

[0061] The present invention will be specifically explained below based on test examples, but the present invention is not limited to these.

[0062] [Test Example 1: Measurement of Contact Angle] Each ophthalmic composition (eye drops; 100 mL) shown in Table 1 was prepared by a conventional method. The units of each component in Table 1 are all w / v % unless otherwise specified in the table. A droplet (approximately 1 μL) of each prepared ophthalmic composition was dropped onto a stainless steel metal plate (Ferrule cap Type CLF-B), and the contact angle (static contact angle) with the metal was measured 0.5 seconds after the drop using an automatic contact angle meter (Drop Master, DM-A501). The contact angle was measured 10 times for each ophthalmic composition, and the average value was calculated to determine the contact angle of each ophthalmic composition. A larger contact angle indicates better drainage, allowing for more accurate filling of the container. The improvement rate of the contact angle of each ophthalmic composition relative to Reference Example 1-1 was calculated according to the following formula 1. The results are shown in Table 1. [Formula 1] Contact angle improvement rate (%) = {(contact angle of each ophthalmic composition - contact angle of Reference Example 1-1) / contact angle of Reference Example 1-1} × 100 The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (Seikagaku Corporation, weight-average molecular weight 20,000).

[0063] [Table 1]

[0064] It was confirmed that when benzalkonium chloride was added to an ophthalmic composition containing 3.0 w / v% sodium chondroitin sulfate, the contact angle decreased and the dry-off significantly worsened (Comparative Example 1-2).On the other hand, it was confirmed that when zinc chloride or disodium edetate was added to an ophthalmic composition containing 3.0 w / v% sodium chondroitin sulfate, the improvement rate of the contact angle increased and the dry-off was improved (Examples 1-1 and 1-2).

[0065] It was confirmed that the ophthalmic compositions of Examples 1-1 and 1-2 had significantly higher preservative effects than the ophthalmic composition of Comparative Example 1-1.

[0066] [Test Example 2: Protein adhesion inhibition test] Each ophthalmic composition (eye drops; 100 mL) shown in Table 2 was prepared by a conventional method. The unit of each component in Table 2 is w / v %. Contact lenses (etafilcon A lenses (manufactured by Johnson & Johnson, trade name: 2 Week Acuvue, FDA contact lens classification: Group IV)) were washed with 100 mL of saline in a beaker, and the lenses were wiped dry with Bemcot (registered trademark) Lint-Free. The lenses were then immersed in 2 mL of each ophthalmic composition in a 24-well plate and shaken for 30 minutes in a shaker set at 34°C and 120 rpm. In accordance with FDA guidelines, 2 mL of protein solution (a buffer solution (sodium chloride: 0.9 w / v%, sodium dihydrogen phosphate dihydrate: 0.045 w / v%) to which egg white lysozyme, bovine serum albumin, and bovine globulin were added to make concentrations of 0.120 w / v%, 0.388 w / v%, and 0.161 w / v%) was dispensed into each 24-well plate containing the contact lenses and each ophthalmic composition, and the plates were shaken at 34°C and 120 rpm for 30 minutes. The contact lenses were then removed, immersed in 100 mL of saline for approximately 1 second to rinse off excess protein solution, drained, and wiped dry with Bemcot® Lint-Free. The contact lenses were then immersed in the protein solution and shaken at 34°C and 120 rpm for 1 hour. The contact lenses were then removed and quickly immersed (for approximately 1 second) in 100 mL of physiological saline to rinse off excess test solution. After draining, the lenses were wiped dry with a Bemcot® Lint-Free wipe and then immersed in 2 mL of protein separation solution (aqueous solution containing 1% sodium carbonate and 1% SDS) in a 24-well plate. The lenses were shaken at room temperature at 120 rpm for approximately 1 hour, and the proteins adsorbed to the contact lenses were recovered in the protein separation solution. The amount of protein in the protein separation solution was quantified using albumin as the standard using a BCA assay kit (Thermo Scientific, Pierce #23225) and calculated as an albumin equivalent value, which was used as the protein adsorption amount on the contact lenses. The protein adhesion inhibition rate of each ophthalmic composition relative to Reference Example 2-1 was calculated according to the following formula 2. The results are shown in Table 2. [Formula 2] Protein adhesion inhibition rate (%)={(protein adsorption amount of Reference Example 2-1−protein adsorption amount of each ophthalmic composition) / protein adsorption amount of Reference Example 2-1}×100 The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (Seikagaku Corporation, weight-average molecular weight 20,000).

[0067] [Table 2]

[0068] Compared with Reference Example 2-1, which does not contain sodium chondroitin sulfate, Reference Example 2-2, which contains 0.5 w / v% sodium chondroitin sulfate, showed an inhibitory effect on protein adhesion to contact lenses, while Comparative Example 2-1, which contains 3.0 w / v% sodium chondroitin sulfate, showed a greater degree of protein adhesion.On the other hand, Example 2-1, in which zinc chloride was blended with 3.0 w / v% sodium chondroitin sulfate, showed an improved protein adhesion inhibition rate, and Example 2-2, in which disodium edetate was blended with 3.0 w / v% sodium chondroitin sulfate, showed a significantly improved protein adhesion inhibition rate.

[0069] Test Example 3: Protein Cleaning Test Each ophthalmic composition (eye drops; 100 mL) shown in Table 3 was prepared by a conventional method. The unit of each component in Table 3 is w / v %. In accordance with FDA guidelines, 2 mL of protein solution (a buffer solution (sodium chloride: 0.9 w / v%, sodium dihydrogen phosphate dihydrate: 0.045 w / v%) containing 0.120 w / v% egg white lysozyme, 0.388 w / v% bovine serum albumin, and 0.161 w / v% bovine globulin) was dispensed into 10 mL glass screw vials. Next, soft contact lenses (etafilcon A lenses (Johnson & Johnson, trade name: 2-week Acuvue)) were washed with 100 mL of saline in a beaker, wiped dry with Bemcot® Lint-Free, and then immersed individually in the protein solution. The contact lenses were then shaken at 34°C and 120 rpm for 8 hours. The contact lenses were removed, immersed in 100 mL of physiological saline for approximately 1 second to rinse off excess protein solution, then drained and wiped with Bemcot® Lint-Free. Each lens was then immersed individually in 2 mL of each ophthalmic composition in a 10 mL glass screw vial, and shaken at 34°C and 120 rpm for approximately 16 hours. The contact lenses were then removed, immersed in 100 mL of physiological saline for approximately 1 second to rinse off excess ophthalmic composition, drained, wiped with Bemcot® Lint-Free, and then immersed in 2 mL of protein separation solution (aqueous solution containing 1% sodium carbonate and 1% SDS) in a 10 mL glass screw vial. The lenses were shaken at room temperature for approximately 1 hour in a shaker set at 120 rpm, and the proteins adsorbed to the contact lenses were recovered in the protein separation solution. Using a BCA assay kit (Thermo Scientific, Pierce #23225), the amount of protein in the protein separation solution was quantified as an albumin equivalent value by quantifying it using albumin as a standard, and this was taken as the amount of protein adsorbed onto the contact lens. The improvement rate of protein removal for each ophthalmic composition relative to Reference Example 3-1 was calculated according to the following formula 3. The results are shown in Table 3. [Formula 3] Protein cleaning improvement rate (%)={(protein adsorption amount of Reference Example 3-1−protein adsorption amount of each ophthalmic composition) / protein adsorption amount of Reference Example 3-1}×100 The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (Seikagaku Corporation, weight-average molecular weight 20,000).

[0070] [Table 3]

[0071] In Comparative Example 3-1 containing zinc chloride, the protein cleaning effect was reduced compared to Reference Example 3-1 not containing zinc chloride. On the other hand, in Example 3-1 containing zinc chloride and 3.0 w / v% sodium chondroitin sulfate, the protein cleaning improvement rate was confirmed to be significantly improved compared to Reference Example 3-1 not containing zinc chloride. In Comparative Example 3-2, which contained disodium edetate, the protein cleaning effect was slightly improved compared to Reference Example 3-1, which did not contain disodium edetate.On the other hand, in Example 3-2, which contained disodium edetate and 3.0 w / v% sodium chondroitin sulfate, it was confirmed that the protein cleaning improvement rate was significantly improved compared to Reference Example 3-1, which did not contain disodium edetate.

[0072] [Test Example 4: Evaluation of Variation in Drop Amount] Each ophthalmic composition (eye drops; 100 mL) shown in Table 4 was prepared by a conventional method. The unit of each component in Table 4 is w / v %. Next, 10 mL of each prepared ophthalmic composition was filled into a 10 mL polyethylene terephthalate eye drop container, and a polyethylene nozzle was attached to the container. The polyethylene nozzle was suitable for dispensing 30 to 50 μL. The eye drops in the container were dispensed while held horizontally, and the weight of each dispensed drop was measured. This procedure was repeated 10 times to determine the average dispensed amount (AVG: mg) and standard deviation (SD: mg), and the variation in dispensed amount (coefficient of variation CV: %) was calculated using the following formula 4. Using each obtained coefficient of variation, the suppression rate of variation in dispensed amount for each ophthalmic composition relative to Reference Example 4-1 was calculated according to the following formula 5. The results are shown in Table 4. [Formula 4] Variation in drip volume (coefficient of variation CV:%) = (SD / AVG) x 100 [Equation 5] Drop amount variation suppression rate (%)={(coefficient of variation of Reference Example 4-1−coefficient of variation of each ophthalmic composition) / coefficient of variation of Reference Example 4-1}×100 The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (Seikagaku Corporation, weight-average molecular weight 20,000).

[0073] [Table 4]

[0074] In the ophthalmic compositions containing zinc chloride or disodium edetate, the variation in the amount of drops applied was worse than that in the ophthalmic compositions not containing zinc chloride or disodium edetate (Comparative Examples 4-1 and 4-2).In contrast, it was confirmed that the variation in the amount of drops applied was significantly suppressed by adding 3.0 w / v% sodium chondroitin sulfate to the ophthalmic compositions containing zinc chloride or disodium edetate (Examples 4-1 and 4-2).

[0075] [Test Example 5: Contact Angle Measurement (2)] Each ophthalmic composition (eye drops; 100 mL) shown in Table 5 was prepared by a conventional method. The units of each component in Table 5 are all w / v % unless otherwise specified in the table. The contact angle of each ophthalmic composition was measured in the same manner as in Test Example 1 above, and the contact angle improvement rate of each ophthalmic composition relative to Reference Example 5-1 was calculated according to the following formula 6. The viscosity and osmotic pressure of each ophthalmic composition were also measured. The viscosity was measured at 20°C using a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34' x R24) at a rotation speed of 100 rpm. The osmotic pressure was measured with reference to the osmotic pressure measurement method (freezing point depression method) described in the Japanese Pharmacopoeia. The results are shown in Table 5. [Formula 6] Contact angle improvement rate (%)={(contact angle of each ophthalmic composition−contact angle of Reference Example 5-1) / contact angle of Reference Example 5-1}×100 The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (Seikagaku Corporation, weight-average molecular weight 20,000).

[0076] [Table 5]

[0077] It was confirmed that the ophthalmic composition of Comparative Example 5-1, which contained 1.0 w / v% sodium chondroitin sulfate, had a smaller contact angle and significantly worsened drainage compared to the ophthalmic composition of Reference Example 5-1, which did not contain sodium chondroitin sulfate.On the other hand, it was confirmed that the ophthalmic composition of Example 5-1, which contained 1.0 w / v% sodium chondroitin sulfate and added zinc chloride, had an increased contact angle improvement rate and improved drainage compared to the ophthalmic composition of Reference Example 5-1, which did not contain sodium chondroitin sulfate.

[0078] [Test Example 6: Protein Cleaning Test (2)] Each ophthalmic composition (eye drops; 100 mL) shown in Table 6 was prepared by a conventional method. The unit of each component in Table 6 is w / v %. The amount of protein adsorbed to the contact lens for each ophthalmic composition was quantified in the same manner as in Test Example 3, and the improvement rate of protein cleaning for each ophthalmic composition relative to Reference Example 6-1 was calculated according to the following formula 7. The viscosity and osmotic pressure of each ophthalmic composition were also measured in the same manner as in Test Example 5. The results are shown in Table 6. [Formula 7] Protein cleaning improvement rate (%)={(protein adsorption amount of Reference Example 6-1−protein adsorption amount of each ophthalmic composition) / protein adsorption amount of Reference Example 6-1}×100 The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (Seikagaku Corporation, weight-average molecular weight 20,000).

[0079] [Table 6]

[0080] In Example 6-1, in which zinc chloride was blended with 1.0 w / v% sodium chondroitin sulfate, it was confirmed that the protein cleaning improvement rate was significantly improved compared to Reference Example 6-1, which did not contain zinc chloride. In Example 6-2, in which 1.0 w / v% sodium chondroitin sulfate was blended with disodium edetate, it was confirmed that the protein cleaning improvement rate was significantly improved compared to Reference Example 6-1, in which disodium edetate was not blended.

[0081] [Formulation example] Formulation examples are shown in Table 7 below. The units for each ingredient in Table 7 are all w / v % unless otherwise specified in the table.

[0082] [Table 7]

Claims

1. An ophthalmic composition comprising (A) at least one selected from the group consisting of chondroitin sulfate and salts thereof, and (B-2) a chelating agent, and not containing benzalkonium chloride, wherein the content of component (A) is 0.7 w / v % or more based on the total amount of the ophthalmic composition.

2. An ophthalmic composition as described in claim 1, wherein the content of component (A) is 1.0 w / v% or more based on the total amount of the ophthalmic composition.

3. An ophthalmic composition as described in claim 1, wherein the content of component (A) is 3.0 w / v% or more based on the total amount of the ophthalmic composition.

4. An ophthalmic composition described in any one of claims 1 to 3, wherein the component (B-2) is at least one selected from the group consisting of edetic acid and its salts.

5. An ophthalmic composition described in any one of claims 1 to 4, wherein the content of component (B-2) is 0.05 w / v% or more based on the total amount of the ophthalmic composition.

6. An ophthalmic composition described in any one of claims 1 to 5, further containing (C) a buffering agent.

7. An ophthalmic composition described in any one of claims 1 to 6, which does not contain any further preservatives other than benzalkonium chloride.