JP2021075531A - Ophthalmic composition - Google Patents

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

The present invention relates to ophthalmic compositions.

When manufacturing pharmaceutical products such as eye drops and eye wash agents, it is required to fill a container with an accurate amount of chemical solution. Normally, in the filling step, the chemical solution is filled in the container via the filling needle, but by accurately controlling the amount of droplets from the filling needle, the chemical solution can be filled in an accurate amount.

On the other hand, chondroitin sulfate or a salt thereof is blended in an ophthalmic composition for the purpose of promoting energy metabolism, promoting metabolism and cellular respiration to relieve eye strain, replenishing tear components, and the like. (For example, Patent Document 1).

Japanese Unexamined Patent Publication No. 2011-148791

The present inventors have added benzalkonium chloride, which is used as a preservative, to an ophthalmic composition containing a high concentration (for example, 1.0 w / v% or more) of chondroitin sulfate or a salt thereof, from a filling needle. We have found a new problem that the amount of liquid droplets is difficult to control due to poor liquid drainage, and it is not possible to fill a container with an ophthalmic composition having an accurate amount of liquid.

An object of the present invention is to provide an ophthalmic composition which contains chondroitin sulfate or a salt thereof in a high concentration and can fill a container with a more accurate amount of liquid while ensuring antiseptic properties.

The present inventors ensure antiseptic properties by adding zinc chloride or edetic acid or a salt thereof to an ophthalmic composition containing at least one selected from the group consisting of chondroitin sulfate and a salt thereof at a high concentration. While doing so, it has been found that the drainage from the filling needle is improved and the container can be filled with a more accurate amount of the ophthalmic composition. The present invention is based on this finding and provides the following inventions.

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

According to the present invention, it is possible to provide an ophthalmic composition which contains chondroitin sulfate or a salt thereof in a high concentration and can fill a container with a more accurate amount of liquid while ensuring antiseptic properties. The ophthalmic composition of the present invention is preferable because it does not contain a preservative typified by benzalkonium chloride.

Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

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

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

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

The component (A), chondroitin sulfate and a salt thereof, is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. The molecular weight of chondroitin sulfate and its salt is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, but usually, the weight average molecular weight is 10,000 to 100,000. About 5,000 to 50,000, more preferably about 10,000 to 40,000 can be used.

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

As the chondroitin sulfate and its salt, an alkali metal salt of chondroitin sulfate and chondroitin sulfate is preferable, chondroitin sulfate and sodium chondroitin sulfate are more preferable, and sodium chondroitin sulfate is further preferable.

Commercially available chondroitin sulfate and salts thereof can also be used. Chondroitin sulfate and a salt thereof may be used alone or in combination of two or more.

The content of the component (A) in the ophthalmic composition according to the present embodiment is 0.7 w / v% or more based on the total amount of the ophthalmic composition. The lower limit of the content of the component (A) is not particularly limited as long as it is 0.7 w / v% or more, and the type of the component (A), the type and content of other compounding components, the use and formulation of the ophthalmic composition. It is appropriately set according to the form and the like. The lower limit of the content of the component (A) is, for example, preferably 0.7 w / v% or more, and 1.0 w / v% or more, from the viewpoint of exerting the effect of the present invention more remarkably. Is 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 the component (A) is not particularly limited, and is appropriately set according to the type of the component (A), the type and content of other compounding components, the use of the ophthalmic composition, the formulation form, and the like. The upper limit of the content of the component (A) is preferably 5.0 w / v% or less, for example, from the viewpoint of more remarkably exerting the effect of the present invention and the feeling of use, 4.0 w. It is more preferably / v% or less, further preferably 3.5 w / v% or less, and even more preferably 3.0 w / v% or less. The content of the component (A) in the ophthalmic composition according to the present embodiment is, for example, 0.7 to 5.0 w / v% and 0.7 to 4.0 w / based on the total amount of the ophthalmic composition. v%, 0.7-3.5w / v%, 0.7-3.0w / v%, 0.7-1.5w / v%, 0.7-1.0w / v%, 1.0 ~ 5.0w / v%, 1.0 ~ 4.0w / v%, 1.0 ~ 3.5w / v%, 1.0 ~ 3.0w / v%, 2.0 ~ 5.0w / v %, 2.0-4.0 w / v%, 2.0-3.5 w / v%, 2.0-3.0 w / v%, 2.5-5.0 w / v%, 2.5- It may be 4.0 w / v%, 2.5 to 3.5 w / v%, or 2.5 to 3.0 w / v%. As another aspect, the content of the component (A) in the ophthalmic composition according to the present embodiment is, for example, 1.0 w / v%, 2.0 w / v%, or 3 based on the total amount of the ophthalmic composition. It may be 0.0 w / v%.

[Component (B)]
In the ophthalmic composition according to the present embodiment, in addition to the component (A), (B) (B-1) zinc chloride (also simply referred to as “component (B-1)”), and (B-2). Each component of (B-1) and (B-2) further contains at least one selected from the group consisting of a chelating agent (also simply referred to as "(B-2) component"). It is also simply referred to as "(B) component"). As the component (B), one type may be used alone, or two or more types may be used in combination.

[(B-1) component]
Zinc chloride as a component (B-1) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

The content of the component (B-1) in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set according to the type and content of other compounding components, the use of the ophthalmic composition, the formulation form, and the like. .. Regarding the content of the component (B-1), from the viewpoint of exerting the effect of the present invention more remarkably, for example, the total content of the component (B-1) is 0.00001 based on the total amount of the ophthalmic composition. It is preferably ~ 0.05 w / v%, more preferably 0.00005 to 0.02 w / v%, further preferably 0.0001 to 0.01 w / v%, and 0.0005 w. It is even more preferably / v% to 0.005 w / v%.

The content ratio of the component (B-1) to the component (A) in the ophthalmic composition according to the present embodiment is not particularly limited, and the type of the component (A), the type and content of other compounding components, and the ophthalmic composition. It is appropriately set according to the intended use and the form of the formulation. Regarding the content ratio of the component (B-1) to the component (A), from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (A) contained in the ophthalmic composition according to the present embodiment is 1. The total content of the component (B-1) is preferably 0.000003 to 0.05 parts by mass, more preferably 0.000017 to 0.02 parts by mass, and 0. It is more preferably 0.0003 to 0.01 parts by mass, and even more preferably 0.00017 to 0.005 parts by mass.

[(B-2) component]
The chelating agent as the component (B-2) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and is not particularly limited. Examples thereof include acetic acid (EDDA), ethylenediaminetriacetic acid, N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), and diethylenetriaminetetraacetic acid (DTPA), and among these, edetic acid or a salt thereof is preferably used. ..

Edetonic acid, also referred to as ethylenediaminetetraacetic acid (EDTA), is a known compound represented by _{C 10} H ₁₆ N ₂ O _8.

Examples of the salt of edetonic acid include alkali metal salts such as sodium edetate, disodium edetate, and tetrasodium edetate, and among these, disodium edetate is preferably used.

The content of the component (B-2) in the ophthalmic composition according to the present embodiment is not particularly limited, and the type of the component (B-2), the type and content of other compounding components, the use and formulation of the ophthalmic composition. It is appropriately set according to the form and the like. Regarding the content of the component (B-2), from the viewpoint of further enhancing the antiseptic effect, for example, the total content of the component (B-2) is 0.01 w / v% or more based on the total amount of the ophthalmic composition. It is more preferably 0.03 w / v% or more, further preferably 0.05 w / v% or more, further preferably 0.07 w / v% or more, and 0. It is particularly preferable that it is .09 w / v% or more. Regarding the content of the component (B-2), from the viewpoint of exerting the effect of the present invention more remarkably, for example, the total content of the component (B-2) is 10 w based on the total amount of the ophthalmic composition. It is preferably / v% or less, more preferably 5 w / v% or less, further preferably 3 w / v% or less, still more preferably 1 w / v% or less, and 0.5 w. It is particularly preferable that it is / v% or less. The content of the component (B-2) in the ophthalmic composition according to the present embodiment is, for example, 0.01 to 10 w / v% and 0.03 to 5 w / v% based on the total amount of the ophthalmic composition. , 0.05 to 3 w / v%, 0.07 to 1 w / v%, or 0.09 to 0.5 w / v%.

The content ratio of the component (B-2) to the component (A) in the ophthalmic composition according to the present embodiment is not particularly limited, and the types of the components (A) and (B-2) and the types of other compounding components are not particularly limited. And, it is appropriately set according to the content, the use of the ophthalmic composition, the formulation form and the like. Regarding the content ratio of the component (B-2) to the component (A), from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (A) contained in the ophthalmic composition according to the present embodiment is 1. The total content of the component (B-2) is preferably 0.003 to 10 parts by mass, more preferably 0.01 to 5 parts by mass, and 0.017 to 3 parts by mass with respect to parts by mass. It is more preferably parts by mass, more preferably 0.023 to 1 part by mass, and particularly preferably 0.03 to 0.5 parts by mass.

[Component (C)]
The ophthalmic composition according to the present embodiment may further contain (C) a buffer (also simply referred to as "component (C)"). When the ophthalmic composition further contains the component (C), the effect according to the present invention is more prominently exhibited.

The buffer is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

Examples of the buffer include an inorganic buffer which is a buffer derived from an inorganic acid and an organic buffer which is a buffer derived from an organic acid or an organic base.

Examples of the inorganic buffer include boric acid buffer, phosphoric acid buffer, carbonic acid buffer and the like. Examples of the borate buffer include boric acid or a salt thereof (alkali boric acid metal salt, alkaline earth borate metal salt, etc.). Examples of the phosphoric acid buffer include phosphoric acid or a salt thereof (alkali metal phosphate, alkaline earth metal phosphate, etc.). Examples of the carbonic acid buffer include carbonic acid or a salt thereof (alkali carbonate metal salt, alkaline earth metal carbonate, etc.). Further, as a borate buffer, a phosphate buffer or a carbonate buffer, a hydrate of borate, phosphate or carbonate may be used. As a more specific example, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, boar sand, etc.) as a borate buffer; phosphoric acid or a salt thereof as a phosphate buffer. Salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); Alternatively, examples thereof include salts thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.).

Examples of the organic buffer include citric acid buffer, acetic acid buffer, lactic acid buffer, succinic acid buffer, Tris buffer, AMPD buffer and the like. Examples of the citric acid buffer include citric acid or a salt thereof (alkaline citric acid metal salt, alkaline earth metal citric acid salt, etc.). Examples of the acetic acid buffer include acetic acid or a salt thereof (alkali metal acetate, alkaline earth metal acetate, etc.). Examples of the lactic acid buffer include lactic acid or a salt thereof (alkaline lactic acid metal salt, alkaline earth metal lactic acid salt, etc.). Examples of the succinic acid buffer include succinic acid or a salt thereof (alkali metal succinate, etc.). Further, as a citrate buffer, an acetate buffer, a lactic acid buffer or a succinic acid buffer, a hydrate of citrate, acetate, lactate or succinate may be used. As a more specific example, citrate or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.) as a citrate buffer; acetic acid as an acetate buffer. Or a salt thereof (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.); as a lactic acid buffer, lactic acid or a salt thereof (sodium citrate, potassium lactic acid, calcium lactate, etc.); Monosodium citrate, disodium citrate, etc.) can be exemplified. Examples of the tris buffer include tromethamole or a salt thereof (trometamole hydrochloride and the like). Examples of the AMPD buffer include 2-amino-2-methyl-1,3-propanediol or a salt thereof.

The buffer includes a boric acid buffer (for example, a combination of boric acid and boric acid), a phosphate buffer (for example, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), and a Tris buffer (for example, a combination of boric acid and sodium dihydrogen phosphate). , Trometamol) is preferred, boric acid buffer is more preferred, boric acid and salts thereof are even more preferred, and the combination of boric acid and boric acid is even more preferred.

As the buffering agent, a commercially available one may be used. The buffer may be used alone or in combination of two or more.

The content of the component (C) in the ophthalmic composition according to the present embodiment is not particularly limited, and depends on the type of the component (C), the type and content of other compounding components, the use of the ophthalmic composition, the formulation form, and the like. Is set as appropriate. Regarding the content of the component (C), from the viewpoint of exerting the effect of the present invention more remarkably, for example, the total content of the component (C) is 0.01 to 10 w / v based on the total amount of the ophthalmic composition. %, More preferably 0.05 to 5 w / v%, and even more preferably 0.1 to 3 w / v%.

The content ratio of the component (C) to the component (A) in the ophthalmic composition according to the present embodiment is not particularly limited, and the types of the component (A) and the component (C), the types and contents of other compounding components, It is appropriately set according to the use of the ophthalmic composition, the form of the preparation, and the like. Regarding the content ratio of the component (C) to the component (A), from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (A) contained in the ophthalmic composition according to the present embodiment is 1 part by mass. On the other hand, the total content of the component (C) is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and 0.5 to 3 parts by mass. Is even more preferable.

[Component (D)]
The ophthalmic composition according to the present embodiment may further contain (D) an isotonic agent (also simply referred to as "component (D)"). When the ophthalmic composition further contains the component (D), the effect according to the present invention is more prominently exhibited. The component (D) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

Examples of the isotonic agent as the component (D) include an ionic isotonic agent and a nonionic isotonic agent.

Examples of the ionic isotonic agent include inorganic salts such as calcium chloride, magnesium chloride, sodium chloride, potassium chloride, ammonium chloride, calcium sulfate, magnesium sulfate, sodium sulfate and potassium sulfate, monoethanolamine, diethanolamine, and triethanolamine. Ethanolamine can be mentioned. Among the ionic isotonic agents, sodium chloride and monoethanolamine are preferable from the viewpoint of exerting the effect of the present invention more remarkably.

Examples of the nonionic isotonic agent include alcohols such as glycerin, propylene glycol, polyethylene glycol (400, 4000, 6000, etc.), glucose, sorbitol, mannitol, xylitol, and trehalose. Among the nonionic isotonic agents, mannitol is preferable from the viewpoint of exerting the effect of the present invention more remarkably and preventing the stickiness of the preparation.

Commercially available isotonic agents can also be used. The tonicity agent may be used alone or in combination of two or more.

The total content of the component (D) in the ophthalmic composition according to the present embodiment is not particularly limited, and may vary depending on the type of the component (D), the type and content of other compounding components, the use of the ophthalmic composition, the formulation form, and the like. It is set as appropriate according to the situation. Regarding the content of the component (D), from the viewpoint of exerting the effect of the present invention more remarkably, for example, the total content of the component (D) is 0.0001 to 10 w / v based on the total amount of the ophthalmic composition. %, More preferably 0.0005-7w / v%, further preferably 0.001-6w / v%, further preferably 0.005-5w / v%. More preferably, 0.005 to 4 w / v% is particularly preferable, 0.005 to 3 w / v% is more preferable, and 0.01 to 2 w / v% is even more preferable. It is even more preferably 0.01 to 1.5 w / v%, and most preferably 0.05 to 1 w / v%.

The content ratio of the component (D) to the component (A) in the ophthalmic composition according to the present embodiment is not particularly limited, and the types of the components (A) and (D), the types and contents of other compounding components, It is appropriately set according to the use of the ophthalmic composition, the form of the preparation, and the like. Regarding the content ratio of the component (D) to the component (A), from the viewpoint of exerting the effect of the present invention more remarkably, for example, the total content of the component (A) contained in the ophthalmic composition according to the present embodiment is 1 mass. The total content of the component (D) is preferably 0.00003 to 10 parts by mass, more preferably 0.00017 to 7 parts by mass, and 0.0003 to 6 parts by mass. It is even more preferably 0.0017 to 5 parts by mass, particularly preferably 0.0017 to 4 parts by mass, and even more preferably 0.0017 to 3 parts by mass. It is even more preferably 0.003 to 2 parts by mass, even more preferably 0.003 to 1.5 parts by mass, and most preferably 0.016 to 1 part by mass.

The ophthalmic composition according to this embodiment does not contain benzalkonium chloride. As a result, side effects such as inflammation of the cornea and conjunctiva caused by benzalkonium chloride and allergies can be suppressed, and the effects of the present invention can be more prominently exhibited.

The pH of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable range. The pH of the ophthalmic composition according to the present embodiment may be, for example, 4.0 to 9.5, preferably 4.0 to 9.0, and 4.5 to 9.0. Is more preferably 4.5 to 8.5, further preferably 5.0 to 8.5, particularly preferably 5.5 to 8.0, and 6.0. It is particularly more preferably ~ 7.8.

The ophthalmic composition according to the present embodiment can be adjusted to an osmotic pressure ratio within a range acceptable to the living body, if necessary. The appropriate osmotic pressure ratio varies depending on the application site, dosage form, etc., but from the viewpoint of exerting the effect of the present invention more remarkably, for example, it is preferably 0.05 to 6, and more preferably 0.4 to 5. It is preferably 0.6 to 3, and even more preferably 0.8 to 2. The osmotic pressure ratio may be 0.3 to 4, 0.5 to 3, or 0.7 to 1.4. The osmotic pressure can be adjusted by a method known in the art using inorganic salts, polyhydric alcohols and the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (osmotic pressure of 0.9 w / v% sodium chloride aqueous solution) based on the 17th revised Japanese Pharmacy, and the osmotic pressure is the osmotic pressure measurement method described in the Japanese Pharmacy. Measure with reference to (freezing point depression method). The standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) is prepared by drying sodium chloride (standard reagent of the Japanese Pharmacopoeia) at 500 to 650 ° C. for 40 to 50 minutes and then in a desiccator (silica). Allow to cool, weigh accurately 0.900 g, dissolve in purified water to prepare exactly 100 mL, or use a commercially available standard solution for measuring osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution).

The viscosity of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable range. As the viscosity of the ophthalmic composition according to the present embodiment, for example, the viscosity at 20 ° C. measured with a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor; 1 ° 34'x R24) is 0. .1 to 10000 mPa · s, more preferably 1 to 3000 mPa · s, further preferably 1 to 1000 mPa · s, even more preferably 1 to 100 mPa · s, 1 It is particularly preferably about 50 mPa · s, more preferably 1 to 10 mPa · s, and even more preferably 1.3 to 5 mPa · s. Further, the viscosity may be 1 to 5 mPa · s, 1 to 4 mPa · s, or 1 to 3 mPa · s.

The ophthalmic composition according to the present embodiment contains an appropriate amount of a combination of various pharmacologically active ingredients and components selected from physiologically active ingredients in addition to the above components, as long as the effects of the present invention are not impaired. May be good. The component is not particularly limited, and for example, the active ingredient in an ophthalmic drug described in the 2012 edition of the OTC drug manufacturing and marketing approval standard (supervised by the Regulatory Science Society) can be exemplified. Specific examples of the components used in ophthalmic drugs include the following components.
Anti-allergic agents: for example, sodium cromoglycate, tranilast, potassium pemirolast, etc.
Antihistamines: for example, diphenhydramine hydrochloride, iproheptine, chlorpheniramine maleate, levocabastine hydrochloride, ketotifen fumarate, pemirolast potassium, olopatadine hydrochloride and the like.
Anti-inflammatory agents: for example, methyl salicylate, glycol salicylate, allantin, tranexamic acid, lysoteam, lysozyme chloride, indomethacin, pranoprofen, ibuprofen, ibuprofen piconol, ketoprofen, felbinac, bendazac, piroxicam, bufexamac, butyl flufenamic acid, epsilon- Aminocaproic acid, velberin chloride, velverin sulfate, sodium azulene sulfonate, etc.
Steroids: For example, fluticasone propionate, fluticasone furancarboxylic acid, mometasone furancarboxylic acid, beclomethasone propionate, flunisolide and the like.
Decongestant: for example, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, ephedrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephrine hydrochloride and the like.
Eye muscle regulators: For example, cholinesterase inhibitors having an active center similar to acetylcholine, specifically neostigmine methylsulfate, tropicamide, helenien, atropine sulfate and the like.
Vitamins: For example, retinyl acetate, retinol palmitate, tocopherol acetate, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, ascorbate, sodium ascorbate and the like.
Amino acids: For example, glutamic acid, aspartic acid, arginine, glycine, aminoethylsulfonic acid (taurine), trimethylglycine and salts thereof.
Astringent: For example, zinc oxide, zinc lactate, zinc sulfate, etc.
Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidin and salts thereof.

For the ophthalmic composition according to the present embodiment, as long as the effect of the present invention is not impaired, various additives are appropriately selected according to a conventional method according to the use and the formulation form, and one or more. May be contained in combination in an appropriate amount. Examples of such additives include various additives described in the Encyclopedia of Pharmaceutical Additives 2007 (edited by the Japan Pharmaceutical Additives Association). The following additives can be mentioned as typical components.
Carrier: An aqueous solvent such as water or hydrous ethanol.
Base: For example, octyldodecanol, titanium oxide, potassium bromide, plastic base, etc.
pH adjuster: For example, hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, diisopropanolamine and the like.
Stabilizers: For example, sodium formaldehyde sulfoxylate (longalit), sodium hydrogen sulfite, sodium pyrosulfite, aluminum monostearate, glycerin monostearate, cyclodextrin, monoethanolamine, dibutylhydroxytoluene and the like.
Thickeners other than the component (A): For example, cellulose-based polymer compounds (for example, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, etc.), polyvinyl-based polymer compounds (polypolypyrrolidone, polyvinyl alcohol, etc.) , Carboxyvinyl polymer, guar gum, hydroxypropyl guar gum, arabic rubber, carrageenan, xanthan gum, agar, alginic acid and its salts (sodium salt, etc.), mucopolysaccharides (eg, heparin analogs, heparin, heparin sulfate, heparan sulfate, heparinoid Hyaluronic acid and its salts (sodium salts, etc.)), starch, chitin and its derivatives, chitosan and its derivatives, carrageenan and the like.
Sugars: For example, glucose, cyclodextrin, etc.
Anionic surfactants: for example, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl ether sulfate, alkylbenzene sulfonate, alkyl sulfate, N-acyl taurine salt and the like.
Amphoteric surfactant: for example, betaine lauryldimethylaminoacetate.
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, chloro. Butanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically) , Polyhexanide hydrochloride (polyhexamethylene biguanide), alexidine hydrochloride, etc.), Gloquil (trade name manufactured by Rhodia), etc. From the viewpoint of further enhancing the effect of the present invention, the ophthalmic composition according to the present embodiment preferably does not contain a preservative other than benzalkonium chloride in addition to benzalkonium chloride.

From the viewpoint that the effect of the present invention can be remarkably exhibited, the ophthalmic composition according to the present embodiment has sodium cromoglycate, phenylephrine hydrochloride, planoprofen, allantin, chlorpheniramine maleate, naphazoline, tetrahydrozoline hydrochloride, neostigmine methyl. It preferably does not contain at least one selected from the group consisting of sulfate, potassium sorbate and chlorhexidine gluconate.

The ophthalmic composition according to the present embodiment may be an aqueous composition (mainly containing an aqueous or hydrophilic composition as a base or carrier), or an oily composition (oily or hydrophobic as a base or carrier). (Mainly including those). When the ophthalmic composition is an aqueous composition, the water content is preferably 50% by weight or more, more preferably 75% by weight or more, and more preferably 80% by weight, based on the total amount of the ophthalmic composition, for example. It is more preferably 50% by weight or more, further preferably 85% by weight or more, and particularly preferably 90% by weight or more. When the ophthalmic composition is an aqueous composition, the water content is preferably less than 100% by weight, preferably 99.5% by weight or less, based on, for example, the total amount of the ophthalmic composition. More preferably, it is 99.2% by weight or less, further preferably 99.0% by weight or less, particularly preferably 97.0% by weight or less, and 96.5% by weight or less. Most preferably. When the ophthalmic composition is an oily composition, the water content is preferably less than 50% by weight, more preferably 30% by weight or less, based on the total amount of the ophthalmic composition, for example, 20% by weight. It is more preferably 0% by weight or less. The ophthalmic composition according to this embodiment is preferably an aqueous composition.

The water used in the ophthalmic composition according to the present embodiment may be pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such water include distilled water, normal water, purified water, sterilized purified water, water for injection, distilled water for injection, and the like. These definitions are based on the 17th revised Japanese Pharmacopoeia.

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

The ophthalmic composition according to the present embodiment can take various dosage forms depending on the purpose, and examples thereof include liquid preparations, gel preparations, semi-solid preparations (ointments, etc.) and the like. Among these, a liquid agent is preferable, and an aqueous liquid agent is more preferable.

The ophthalmic composition according to the present embodiment is, for example, an eye drop (also referred to as an eye drop or an eye drop; the eye drop includes an artificial tear solution, an eye drop that can be instilled while wearing contact lenses), an eye wash. (Also referred to as eye drops or eye drops. The eye drops include eye drops that can be washed while wearing contact lenses.), Composition for contact lenses [Contact lens wearing solution, composition for contact lens care (contact lenses) Disinfectants, preservatives for contact lenses, cleaning agents for contact lenses, cleaning preservatives for contact lenses), contact lens wearing eye drops, etc. used for both contact lens wearing liquids and eye drops while wearing contact lenses] Can be used as. Preferable examples of the ophthalmic composition according to the present embodiment include eye drops, eye wash agents, and composition for contact lenses, and more preferable examples are eye drops that can be instilled during contact lens wearing and contact lens wearing. Examples thereof include eye drops that can be washed, contact lens wearing liquids, and contact lens wearing eye drops, and more preferable examples include eye drops that can be instilled while wearing contact lenses. The "contact lens" includes a hard contact lens and a soft contact lens (including both ionic and non-ionic, and both a silicone hydrogel contact lens and a non-silicone hydrogel contact lens).
In addition, in this specification, "soft contact lenses" means "for soft contact lenses and soft contact lenses" notified by the Chief of Examination and Management Division, Pharmaceutical Safety Bureau, Ministry of Health, Labor and Welfare (then Ministry of Health and Welfare) dated March 31, 1999. This is a classification of soft contact lenses based on the "classification method of soft contact lenses" stipulated in "Handling of materials to be attached when applying for approval of manufacturing (import) of disinfectants". Here, soft contact lenses are classified based on the water content, the molar% of the monomer having an anion, and the like. For example, soft contact lenses belonging to Group IV have a common property that the water content is 50% or more and the molar% of the monomer having an anion among the constituent monomers of the raw material polymer is 1% or more. This classification follows the FDA (US Food and Drug Administration) classification method for soft contact lenses.

When the ophthalmic composition according to the present embodiment is an eye drop, the effect according to the present invention can be exerted more remarkably. Therefore, the ophthalmic composition is preferably an eye drop that can be instilled while wearing contact lenses, and soft contact. It is more preferable that it is an eye drop that can be instilled while wearing a lens (eye drop for soft contact lenses), and it is further preferable that it is used as an ophthalmic composition for group IV soft contact lenses in the FDA contact lens classification. When the ophthalmic composition according to the present embodiment is an eye drop, the dosage and administration thereof is not particularly limited as long as it is effective and has few side effects, but for example, adults (15 years old or older) and For children over 7 years old, 1 to 2 drops at a time, 2 to 4 times a day, or 4 times a day, 1 to 2 drops, 1 to 3 drops, or 2 to 3 drops An example of a method in which the eye drops are instilled 5 to 6 times a day.

In addition, the ophthalmic composition according to the present embodiment is preferably an artificial tear solution because the effect according to the present invention can be exerted more remarkably. When the ophthalmic composition according to the present embodiment is artificial tears, the ophthalmic composition is an anti-inflammatory agent, an antiallergic agent, an antihistamine agent, a steroid agent, a decongestant, an eye muscle regulating agent, a vitamin agent, and a convergence. It is preferable that the agent, sulfamethoxazole, sulfisoxazole, and sulfisomidin are not contained.

The ophthalmic composition according to the present embodiment is provided in an arbitrary container. The container for accommodating the ophthalmic composition according to the present embodiment is not particularly limited, and may be made of glass or plastic, for example. It is preferably made of plastic. Examples of the plastic include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, a copolymer of polyimide and the monomers constituting these, and a mixture of two or more of these. Polypropylene, polyethylene and polyethylene terephthalate are preferable, and polyethylene terephthalate is more preferable. Further, the container for accommodating the ophthalmic composition according to the present embodiment may be a transparent container in which the inside of the container can be visually recognized, or an opaque container in which the inside of the container is difficult to visually recognize. A transparent container is preferable. Here, the "transparent container" includes both a colorless transparent container and a colored transparent container.

A nozzle may be attached to the container containing the ophthalmic composition according to the present embodiment. The material of the nozzle is not particularly limited, and may be made of glass or plastic, for example. It is preferably made of plastic. Examples of the plastic include polybutylene terephthalate, polyethylene, polypropylene, polyethylene naphthalate, a copolymer of the monomers constituting these, and a mixture of two or more of these. As the material of the nozzle, polypropylene, polyethylene, polyethylene terephthalate, and polyethylene naphthalate are preferable, and polyethylene is more preferable, from the viewpoint of further enhancing the effect of the present invention.

The container for accommodating the ophthalmic composition according to the present embodiment may be a multi-dose type containing a plurality of uses, or a unit-dose type containing a single use. , The multi-dose type is preferable because the effect of the present invention can be exerted more remarkably.

Hereinafter, the present invention will be specifically described based on Test Examples, but the present invention is not limited thereto.

[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 unit of each component in Table 1 is w / v% except for those specified in the table.
The droplet amount (about 1 μL) of each prepared ophthalmic composition was dropped onto a stainless metal plate (ferrule cap TypeCLF-B), and dropped using an automatic contact angle meter (Drop Master, DM-A501). The contact angle (static contact angle) with respect to the metal after 5 seconds was measured. The contact angle of each ophthalmic composition was measured 10 times, and the average value was calculated to obtain the contact angle of each ophthalmic composition. Here, it is shown that the larger the contact angle is, the better the liquid drainage is, and a more accurate liquid amount can be filled in the container.
According to the following formula 1, the contact angle improvement rate of each ophthalmic composition was calculated with respect to Reference Example 1-1. 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
As the sodium chondroitin sulfate, sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight 20,000) was used.

It was confirmed that when benzalkonium chloride was added to an ophthalmic composition containing 3.0 w / v% of sodium chondroitin sulfate, the contact angle was reduced and the liquid drainage was remarkably 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% of sodium chondroitin sulfate, the contact angle improvement rate was increased and the liquid drainage was improved (implementation). Examples 1-1 and 1-2).

It was confirmed that the ophthalmic compositions of Examples 1-1 and 1-2 had a significantly higher antiseptic effect than the ophthalmic compositions of Comparative Example 1-1.

[Test Example 2: Protein adhesion suppression 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%.
Wash contact lenses (etafilcon A lenses (manufactured by Johnson & Johnson, trade name: 2 Week Acuvue, FDA contact lens classification: Group IV)) with 100 mL of saline in a beaker, and Bencott (registered). A lint-free, lint-free, moisturized lens was dipped in each ophthalmic composition containing 2 mL each in a 24-well well plate and shaken for 30 minutes in a shaker set at 34 ° C. and 120 rpm.
According to FDA guidelines, 0.120 w / v% egg white lysozyme in a protein solution (buffer solution (sodium chloride: 0.9 w / v%, sodium dihydrogen phosphate dihydrate: 0.045 w / v%), bovine Serum albumin was added to 0.388 w / v% and bovine globulin was added to 0.161 w / v%), and 2 mL each was dispensed into a 24-well well plate containing contact lenses and each ophthalmic composition. It was shaken for 30 minutes with a shaker set at 34 ° C. and 120 rpm. Next, the contact lens is taken out and immersed in 100 mL of physiological saline for about 1 second to rinse off the excess protein solution, then the water is drained, and the contact lens whose water has been wiped off with Bencott (registered trademark) lint-free is used as the protein solution. It was immersed and shaken for 1 hour in a shaker set at 34 ° C. and 120 rpm. Next, the contact lenses are taken out and quickly (about 1 second) immersed in 100 mL of physiological saline to rinse off excess test solution, drained, and wiped with Bencot® lint-free, and then 24. It was immersed in a protein separation solution (1% sodium carbonate and 1% SDS-containing aqueous solution) containing 2 mL each in a well-well plate. The mixture was shaken at room temperature and a shaker set at 120 rpm for about 1 hour, and the protein adsorbed on the contact lens was 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 calculated as an albumin-equivalent value by quantifying albumin as a standard, and used as the amount of protein adsorbed on contact lenses.
According to the following formula 2, the protein adhesion inhibition rate of each ophthalmic composition was calculated with respect to Reference Example 2-1. 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
As the sodium chondroitin sulfate, sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight 20,000) was used.

Compared with Reference Example 2-1 which does not contain sodium chondroitin sulfate, Reference Example 2-2 containing 0.5 w / v% of sodium chondroitin sulfate showed an effect of suppressing protein adhesion to contact lenses. On the other hand, in Comparative Example 2-1 containing 3.0 w / v% of sodium chondroitin sulfate, further protein adhesion was observed. On the other hand, in Example 2-1 in which zinc chloride was blended with 3.0 w / v% sodium chondroitin sulfate, the protein adhesion suppression rate was improved, and disodium edetate was blended with 3.0 w / v% sodium chondroitin sulfate. In Example 2-2, it was confirmed that the protein adhesion inhibition rate was remarkably improved.

[Test Example 3: Protein washing 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%.
According to FDA guidelines, 0.120 w / v% egg white lysozyme in a protein solution (buffer solution (sodium chloride: 0.9 w / v%, sodium dihydrogen phosphate dihydrate: 0.045 w / v%), bovine Serum albumin was added to 0.388 w / v% and bovine globulin was added to 0.161 w / v%), and 2 mL each was dispensed into a 10 mL glass screw vial. Next, the soft contact lens (etafilcon A lens (manufactured by Johnson & Johnson, trade name: 2 Week Acuvue)) was washed with 100 mL of physiological saline in a beaker to make Bencot (registered trademark) lint-free. The contact lenses were immersed in the above protein solution one by one, and shaken with a shaker set at 34 ° C. and 120 rpm for 8 hours. Take out the contact lens and immerse it in 100 mL of physiological saline for about 1 second to rinse off excess protein solution, drain the water, wipe off the water with Bencot® lint-free, and 2 mL in advance in a 10 mL glass screw vial. Each ophthalmic composition was dipped one by one and shaken with a shaker set at 34 ° C. and 120 rpm for about 16 hours. Next, the contact lens is taken out and immersed in 100 mL of physiological saline for about 1 second to rinse off excess ophthalmic composition, drained, wiped off with Bencott® lint-free, and then made of 10 mL glass. It was immersed in a protein separation solution (an aqueous solution containing 1% sodium carbonate and 1% SDS) containing 2 mL each in a screw vial. The mixture was shaken at room temperature and a shaker set at 120 rpm for about 1 hour, and the protein adsorbed on the contact lens was 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 albumin as a standard, and used as the amount of protein adsorbed on contact lenses.
According to the following formula 3, the protein washing improvement rate of each ophthalmic composition was calculated with respect to Reference Example 3-1. The results are shown in Table 3.
[Formula 3] Protein washing 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
As the sodium chondroitin sulfate, sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight 20,000) was used.

In Comparative Example 3-1 containing zinc chloride, the cleaning effect of the protein was reduced as compared with Reference Example 3-1 not containing zinc chloride. On the other hand, in Example 3-1 in which 3.0 w / v% sodium chondroitin sulfate was blended with zinc chloride, the protein washing improvement rate was significantly improved as compared with Reference Example 3-1 containing no zinc chloride. It was confirmed that.
In Comparative Example 3-2 containing disodium edetate, the cleaning effect of the protein was slightly improved as compared with Reference Example 3-1 not containing disodium edetate. On the other hand, in Example 3-2 in which 3.0 w / v% sodium chondroitin sulfate was blended with disodium edetate, the improvement rate of protein washing was higher than that in Reference Example 3-1 in which disodium edetate was not blended. It was confirmed that there was a significant improvement.

[Test Example 4: Evaluation of variation in dropping 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 of the prepared ophthalmic compositions was filled in a polyethylene terephthalate eye drop container having an internal volume of 10 mL, and a polyethylene nozzle was attached to this container. As the polyethylene nozzle, a nozzle suitable for dropping 30 to 50 μL was used. When the eye drops in a container were dropped in a horizontally oriented state, the drop weight for each drop was measured. From the average dropping amount (AVG: mg) and standard deviation (SD: mg) obtained by repeating this operation 10 times, the variation in dropping amount (coefficient of variation CV:%) was calculated by the following formula 4. Using each of the obtained coefficient of variation, the variation suppression rate of the dropping amount of each ophthalmic composition with respect to Reference Example 4-1 was calculated based on the following formula 5. The results are shown in Table 4.
[Equation 4] Variation in dropping amount (coefficient of variation CV:%) = (SD / AVG) × 100
[Formula 5] Variation suppression rate (%) of dropping amount = {(coefficient of variation of Reference Example 4-1-coefficient of variation of each ophthalmic composition) / coefficient of variation of Reference Example 4-1} × 100
As the sodium chondroitin sulfate, sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight 20,000) was used.

In the ophthalmic composition containing zinc chloride or disodium edetate, the variation in the dropping amount was worsened as compared with the ophthalmic composition not containing zinc chloride or disodium edetate (Comparative Examples 4-1 and 4-2). ). On the other hand, it was confirmed that by adding 3.0 w / v% sodium chondroitin sulfate to the ophthalmic composition containing zinc chloride or disodium edetate, the variation in the dropping amount was remarkably suppressed. (Examples 4-1 and 4-2).

[Test Example 5: Measurement of contact angle (2)]
Each ophthalmic composition (eye drops; 100 mL) shown in Table 5 was prepared by a conventional method. The unit of each component in Table 5 is w / v% except for those specified in the table.
The contact angle of each ophthalmic composition was measured by the same method as in Test Example 1, and the contact angle improvement rate of each ophthalmic composition was calculated with respect to Reference Example 5-1 according to the following formula 6. In addition, the viscosity and osmotic pressure of each ophthalmic composition were 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
As the sodium chondroitin sulfate, sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight 20,000) was used.

The ophthalmic composition of Comparative Example 5-1 containing 1.0 w / v% of sodium chondroitin sulfate had a smaller contact angle and was liquid as compared with the ophthalmic composition of Reference Example 5-1 containing no sodium chondroitin sulfate. It was confirmed that the cutting was significantly worsened. On the other hand, the ophthalmic composition of Example 5-1 in which zinc chloride was added to the ophthalmic composition containing 1.0 w / v% of sodium chondroitin sulfate was the same as that of the ophthalmic composition of Reference Example 5-1 in which sodium chondroitin sulfate was not added. In comparison, it was confirmed that the contact angle improvement rate was increased and the liquid drainage was improved.

[Test Example 6: Protein washing 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 protein adsorption amount of each ophthalmic composition to the contact lens was quantified by the same method as in Test Example 3, and the protein cleaning improvement rate of each ophthalmic composition was calculated with respect to Reference Example 6-1 according to the following formula 7. In addition, the viscosity and osmotic pressure of each ophthalmic composition were measured by the same method as in Test Example 5 above. The results are shown in Table 6.
[Formula 7] Protein washing 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
As the sodium chondroitin sulfate, sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight 20,000) was used.

In Example 6-1 in which 1.0 w / v% sodium chondroitin sulfate was blended with zinc chloride, the protein washing improvement rate was significantly improved as compared with Reference Example 6-1 containing no zinc chloride. confirmed.
In Example 6-2 in which 1.0 w / v% sodium chondroitin sulfate was blended with disodium edetate, the improvement rate of protein washing was remarkable as compared with Reference Example 6-1 in which disodium edetate was not blended. It was confirmed that it would improve.

[Formulation example]
Table 7 below shows an example of the formulation. The unit of each component in Table 7 is w / v% except for those specified in the table.

Claims (7)

At least one selected from the group consisting of (A) chondroitin sulfate and a salt thereof, and at least one selected from the group consisting of (B) (B-1) zinc chloride and (B-2) chelating agent. , And benzalkonium chloride-free ophthalmic composition, wherein the content of the component (A) is 0.7 w / v% or more based on the total amount of the ophthalmic composition. .. The ophthalmic composition according to claim 1, wherein the content of the component (A) is 1.0 w / v% or more based on the total amount of the ophthalmic composition. The ophthalmic composition according to claim 1, wherein the content of the component (A) is 3.0 w / v% or more based on the total amount of the ophthalmic composition. (B-2) The ophthalmic composition according to any one of claims 1 to 3, wherein the component is at least one selected from the group consisting of edetic acid and a salt thereof. The ophthalmic composition according to any one of claims 1 to 4, wherein the content of the component (B-2) is 0.05 w / v% or more based on the total amount of the ophthalmic composition. (C) The ophthalmic composition according to any one of claims 1 to 5, further containing a buffer. The ophthalmic composition according to any one of claims 1 to 6, further containing no preservative other than benzalkonium chloride.