JP6904289B2 - Aqueous ophthalmic composition - Google Patents

Description

The present invention relates to an aqueous ophthalmic composition containing a wax ester or a sterol ester.

The tear oil layer is indispensable for maintaining the function of the eye in order to prevent the evaporation of water in the tear and remove foreign substances, and it is necessary to be stable on the surface of the eye in order to fully fulfill its role. Is. This tear oil layer is composed of lipids (meiboms) secreted from the meibomian glands, and the main components are wax esters, sterol esters, phospholipids and the like. On the other hand, these components increase the proportion of saturated lipids due to aging and hormonal changes, affect the stabilization of the tear oil layer, promote the evaporation of the tear water layer, and cause dry eye symptoms. It is also said to be closely related to eye strain. In particular, it is known that in meibomian gland dysfunction, lipid saturation progresses excessively and the above-mentioned symptoms are exacerbated.

Lanolin is known as containing a wax ester or a sterol ester. Lanolin has been conventionally used as a base for eye ointments, but there is a problem that eye ointments have a problem of poor usability such as stickiness as compared with aqueous eye drops. In addition, techniques for blending lanolin with water-soluble eye drops have also been proposed (Patent Document 1: Japanese Patent Application Laid-Open No. 2016-216509), but these can sufficiently supply wax esters and sterol esters to the tear oil layer. There wasn't. On the other hand, if the blending amount is increased in order to increase the supply amount, there is a problem that blurring occurs after suspension and use, and in the suspended preparation, it is judged whether or not foreign matter is mixed in during production. There was a problem such as difficulty.

Japanese Unexamined Patent Publication No. 2016-216509

The present invention has been made in view of the above circumstances, and is a composition for an aqueous ophthalmic composition containing one or more selected from wax esters and sterol esters (hereinafter, may be referred to as component (A)). It is an object of the present invention to provide an aqueous ophthalmic composition in which the component (A) is released from the composition and can be sufficiently supplied to the tear oil layer by being diluted with the tear fluid after instillation and having a high permeability of the ester. ..

As a result of diligent studies to achieve the above object, the present inventors have combined the component (A) with polyoxyethylene hydrogenated castor oil having a specific ethylene oxide chain average addition molar number in a specific ratio. It has been found that the above problems can be solved, and the present invention has been made.

Therefore, the present invention provides the following aqueous ophthalmic compositions.
[1]. An aqueous ophthalmic composition containing (A) one or more selected from wax esters and sterol esters, and (B) polyoxyethylene hydrogenated castor oil having an average addition molar number of ethylene oxide chains of 30 to 40.
[2]. When the compounding mass ratio of the component (A) and the component (B) is N, where the average number of moles of the component (B) is N, (7.5-0.15 × N) ≦ (B) / (A) ≦ The aqueous ophthalmic composition according to [1], which satisfies (17.5-0.25 × N).
[3]. The component (B) is polyoxyethylene hydrogenated castor oil having an average addition molar number of ethylene oxide chains of 30, and the compounding mass ratio of the components (A) and (B) is 3 ≦ (B) / (A). The aqueous ophthalmic composition according to [2], wherein the composition is ≦ 10.
[4]. The component (B) is polyoxyethylene hydrogenated castor oil having an average addition molar number of ethylene oxide chains of 40, and the compounding mass ratio of the components (A) and (B) is 1.5 ≦ (B) / (. A) The aqueous ophthalmic composition according to [2], wherein ≦ 7.5.
[5]. (A) The aqueous ophthalmic composition according to any one of [1] to [4], wherein the component is lanolin.
[6]. (C) The aqueous ophthalmic composition according to any one of [1] to [5], which contains one or more selected from vitamin A and vitamin E.

According to the present invention, the component (A) is released from the composition and can be sufficiently supplied to the tear oil layer when the composition has a high transmittance and is diluted with tears after instillation. An aqueous ophthalmic composition containing the above can be provided.

Hereinafter, the present invention will be described in detail. Hereinafter, the aqueous ophthalmic composition may be simply referred to as a composition.
[(A) component]
The component (A) of the present invention is one or more components selected from wax esters and sterol esters, and one or more of them can be used alone or in combination of two or more.
Wax ester refers to a long-chain compound produced by ester bonding of a higher fatty acid and a higher alcohol. The higher fatty acid is also referred to as a long-chain fatty acid, and among the compounds represented by the general formula RCOOH, a compound in which R has a carbon chain length of 12 or more, preferably a monovalent hydrocarbon group of 12 to 35 can be mentioned. Examples of the higher alcohol include alcohols represented by the general formula R'OH, which are compounds in which R'has a carbon chain length of 6 or more, preferably a monohydric hydrocarbon group of 6 to 35. The R, R'carbon chains may be linear or branched, and may be saturated or unsaturated.

The sterol ester refers to a compound produced by an ester bond between a higher fatty acid and cholesterol or triterpene alcohol. Higher fatty acids are the same as above, and cholesterol is the most representative sterol in animal organisms and is a compound with a steroid skeleton. Triterpene alcohol, also referred to as trimethylsterol, refers to lanosterol and its analogs.

As the component (A), wax ester, cholesterol ester and lanolin are preferable, and lanolin is particularly preferable. Lanolin is derived from secretions that attach to animal hair, especially sheep hair, and is a lipid that closely resembles the composition of the tear oil layer. Lanolin is composed of cholesterol, triterpene alcohols, higher fatty acids, higher alcohols and their esters, namely wax esters and sterol esters.

Examples of lanolin include liquid lanolin, adsorption-purified lanolin, reduced lanolin, lanolin acetate (acetylated lanolin), hydrogenated lanolin alcohol, lanolin fatty acid isopropyl, lanolin fatty acid cholesteryl, liquid acetate lanolin, hydroxylanolin, polyoxyethylene lanolin, lanolin fatty acid, Examples thereof include lanolins such as soft lanolin fatty acid, hard lanolin fatty acid, hard lanolin, lanolin alcohol, and lanolin acetate alcohol, and one type alone or two or more types can be used as appropriate. Of these, purified lanolin is preferable, and purified lanolin from the Japanese Pharmacopoeia is more preferable.

The blending amount of the component (A) is composed from the viewpoint of the transmittance of the composition and the release property of the (A) component from the composition by dilution (hereinafter, may be simply referred to as the release property of the component (A)). 0.001 to 1 W / V% (mass / volume%, g / 100 mL) is preferable, 0.01 to 0.5 W / V% is more preferable, and 0.01 to 0.2 W / V% is further preferable. ..

[(B) component]
Polyoxyethylene hydrogenated castor oil having an average number of moles of ethylene oxide chains added 30 to 40 By using this specific polyoxyethylene hydrogenated castor oil, the transmittance of the composition and the release property of the component (A) are improved. Polyoxyethylene hydrogenated castor oil (POE cured castor oil) is a compound obtained by addition polymerization of ethylene oxide to hydrogenated castor oil, and several types with different average addition moles of ethylene oxide are known. ing. In the present invention, the average number of moles of ethylene oxide added to the polyoxyethylene hydrogenated castor oil is 30 to 40. Specifically, the polyoxyethylene hydrogenated castor oil 30 (numerical values are the average number of moles of ethylene oxide added, The same applies hereinafter), and examples thereof include polyoxyethylene hydrogenated castor oil 40. These polyoxyethylene hydrogenated castor oils can be used alone or in combination of two or more. Among them, polyoxyethylene hydrogenated castor oil 40 is preferable from the viewpoint of (A) component release property.

The blending amount of (B) is preferably 0.01 to 5 W / V%, more preferably 0.02 to 2 W / V% in the composition from the viewpoint of the transmittance of the composition and the release property of the component (A). More preferably, 0.05 to 1 W / V%.

The compounding mass ratio of the component (A) and the component (B) is (7) when the average number of moles of the component (B) added is N from the viewpoint of achieving both the transmittance of the composition and the release property of the component (A). It is preferable to satisfy .5-0.15 × N) ≦ (B) / (A) ≦ (17.5-0.25 × N). The above formula for determining the compounding mass ratio defines the mass ratio of the component (B) to the component (A), and is based on the average number of moles of ethylene oxide chains added to the polyoxyethylene hydrogenated castor oil of the component (B). The compounding mass ratio of (B) / (A) is adjusted so that the permeability of the composition and the release property of the component (A) can be more compatible with each other. For example, when N = 30, 3 ≦ (B) / (A) ≦ 10, and when N = 40, 1.5 ≦ (B) / (A) ≦ 7.5. The meaning of each coefficient is the straight line "Y = -0." That passes through (30, 3) and (40, 1.5) when the Y axis is (B) / (A) and the X axis is N. It is a coefficient of two straight lines "Y = -0.25X + 17.5" that pass through "15X + 7.5", (30,10) and (40,7.5). Although the ratio is a W / V% ratio, it is the same value as the mass ratio.

From the viewpoint of the transmittance of the composition, when N = 30, 4 ≦ (B) / (A) is more preferable, and 5 ≦ (B) / (A) is further preferable. When N = 40, 2 ≦ (B) / (A) is more preferable.
(A) From the viewpoint of component release, when N = 30, (B) / (A) ≦ 8 is more preferable, and (B) / (A) ≦ 5 is even more preferable. When N = 40, (B) / (A) ≦ 6 is more preferable.
Therefore, from the viewpoint of achieving both the transmittance of the composition and the release property of the component (A),
When N = 30, 5 ≦ (B) / (A) ≦ 7 is more preferable, and 4 ≦ (B) / (A) ≦ 6 is even more preferable.
When N = 40, 2 ≦ (B) / (A) ≦ 6 is more preferable.

[(C) component]
The composition of the present invention may further contain one or more selected from (C) Vitamin A and Vitamin E. By blending the component (C), the transmittance of the composition is further improved.
Examples of vitamin A include, for example, vitamin A-containing mixture such as vitamin A oil, vitamin A derivative such as vitamin A fatty acid ester, and the like, in addition to vitamin A itself, and one type alone or two or more types are appropriately combined. Can be used. Specific examples thereof include retinol palmitate, retinol acetate, retinol, retinoic acid, and retinoids. Of these, retinol palmitate is preferred.

As vitamin E, for example, tocopherol, tocotrienol, salts thereof, and derivatives (esters) are collectively used. Specifically, for example, there are d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol and the like, and examples of these derivatives include vitamin E acetate (tocopherol acetate). , Vitamin E nicotinic acid ester, Vitamin E succinic acid ester, Vitamin E linolenic acid ester and the like, and one type alone or two or more types can be used as appropriate. Of these, tocopherol acetate (d-α-tocopherol acetate, dl-α-tocopherol acetate, etc.) is preferable. Vitamin E is preferable as the component (C).

The blending amount of (C) is preferably 0.0001 to 1 W / V%, more preferably 0.001 to 0.5 W / V%, still more preferably 0.01 to 0.1 W / V% in the composition.

[Other ingredients]
The composition of the present invention may contain an appropriate amount of other components as long as the effects of the present invention are not impaired. Other components include oil components other than component (A), surfactants other than component (B), preservatives, sugars, buffers, pH adjusters, tonicity agents, stabilizers, refreshing agents, etc. Examples include polyhydric alcohols, thickeners, drugs and the like. These components can be blended individually by 1 type or in combination of 2 or more types as appropriate. The blending amount of the components shown below is a preferable range when blending.

Examples of the oil component other than the component (A) include castor oil, soybean oil, olive oil, sesame oil, corn oil, palm oil, almond oil, medium-chain fatty acid triglyceride, white vaseline, mixed tocopherol, and liquid paraffin. When the oil component is blended, the blending amount thereof is preferably 0.001 to 1.0 W / V%, more preferably 0.001 to 0.5 W / V%, and 0.001 to 0.25 W / V in the composition. % Is the most preferable.

Examples of the surfactant other than the component (B) include the following nonionic surfactants.
Examples of the polyoxyethylene hydrogenated castor oil other than the component (B) include polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 50, and polyoxyethylene. Examples thereof include cured castor oil 60, polyoxyethylene hydrogenated castor oil 80, and polyoxyethylene hydrogenated castor oil 100.

Polyoxyethylene castor oil (POE castor oil) is a compound obtained by addition polymerization of ethylene oxide to castor oil, and several types are known in which the average number of moles of ethylene oxide added is different. The average number of moles of ethylene oxide added to the polyoxyethylene castor oil is not particularly limited, but is exemplified by 3 to 60 moles. Specifically, polyoxyethylene castor oil 3 (numerical values are the average number of moles of ethylene oxide added, the same applies hereinafter), polyoxyethylene castor oil 10, polyoxyethylene castor oil 20, polyoxyethylene castor oil 35, polyoxyethylene castor oil. Examples thereof include oil 40, polyoxyethylene castor oil 50, and polyoxyethylene castor oil 60.

Polyoxyethylene sorbitan fatty acid ester (POE sorbitan fatty acid ester), polyoxy represented by polysorbate 80 (polyoxyethylene (20) sorbitan oleic acid ester) (the value in parentheses is the average number of moles of ethylene oxide added, the same applies hereinafter). Examples thereof include porox summer represented by ethylene-polyoxypropylene block copolymer (POEPOP glycol), polyethylene glycol monostearate represented by polyethylene glycol monostearate (10), and the like. However, phospholipids such as lecithin, hydrogenated lecithin, phosphatidylcholine, and phosphatidylglycerol, which are difficult to desorb from the interface, affect the release of the component (A). It is preferable that it is substantially not contained because it is difficult to transfer to the liquid oil layer.

When a surfactant other than the component (B) is blended, the blending amount affects the release property of the component (A), so that it is preferably 1.0 W / V% or less, preferably 0.1 W / V% in the composition. The following are more preferable, and it is further preferable that they are substantially not contained.

Among preservatives, examples of preservatives having a hydrophobic portion such as an alkyl chain and a benzene ring include thimerosal, phenylethyl alcohol, alkylaminoethylglycine, chlorhexidine gluconic acid, methyl paraoxybenzoate, ethyl paraoxybenzoate and the like. When a preservative is blended, the blending amount is preferably 0.0001 to 0.5 W / V%. However, since it affects the release property of the component (A), when blended, it is preferably 0.1 W / V% or less, more preferably 0.01 W / V% or less, and substantially not contained in the composition. Is more preferable.

Examples of saccharides include glucose, cyclodextrin, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form, or dl-form. When saccharides are blended, the blending amount thereof is preferably 0.001 to 5.0 W / V%, more preferably 0.001 to 1 W / V%, and further 0.001 to 0.1 W / V% in the composition. preferable.

Examples of the buffer include citric acid, sodium citrate, boric acid, borax, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, glacial acetic acid, tromethamole, sodium hydrogen carbonate and the like. When a buffer is blended, the blending amount thereof is preferably 0.001 to 5.0 W / V%, more preferably 0.001 to 2 W / V%, and further preferably 0.001 to 1 W / V% in the composition. preferable.

Examples of the pH adjuster include an inorganic acid or an inorganic alkaline agent. For example, examples of the inorganic acid include (dilute) hydrochloric acid. Examples of the inorganic alkaline agent include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogencarbonate and the like. The pH of the composition is preferably 3.5 to 8.0, more preferably 5.5 to 8.0. The pH is measured at 25 ° C. using a pH meter (HM-25R, DKK-TOA CORPORATION).

Examples of the tonicity agent include sodium chloride, potassium chloride, calcium chloride, sodium hydrogen carbonate, sodium carbonate, dry sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate and the like. Can be mentioned. From the viewpoint of further improving various symptoms caused by the destabilization of the tear oil layer, it is preferable to add sodium chloride or potassium chloride to make it isotonic. The osmotic pressure ratio of the composition to physiological saline is preferably 0.60 to 2.00, more preferably 0.60 to 1.55, and most preferably 0.83 to 1.20. The osmotic pressure is measured at 25 ° C. using an automatic osmotic pressure gauge (A2O, Advanced Instruments).

Examples of the stabilizer include sodium edetate, sodium edetate hydrate, cyclodextrin, sulfite, dibutylhydroxytoluene and the like. When a stabilizer is blended, the blending amount thereof is preferably 0.001 to 5.0 W / V%, more preferably 0.001 to 1 W / V%, and 0.001 to 0.1 W / V% in the composition. Is even more preferable. It is more preferable that dibutylhydroxytoluene is substantially not contained because it inhibits the separation of the component (A) and the surfactant by diluting the tear fluid and makes it difficult for the component (A) to be supplied to the tear oil layer.

Examples of the refreshing agent include menthol, camphor, borneol, geraniol, cineole, linalool and the like. When a refreshing agent is blended, the blending amount thereof is preferably 0.0001 to 0.2 W / V% in the composition.

Examples of the polyhydric alcohol include glycerin, propylene glycol, butylene glycol, polyethylene glycol and the like. When the polyhydric alcohol is blended, the blending amount is preferably 0.001 to 5.0 W / V%, more preferably 0.001 to 1 W / V%, and 0.001 to 0.1 W / V% in the composition. Is even more preferable.

Examples of the thickener include polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, polyacrylic acid, and carboxyvinyl polymer. When a viscous agent is blended, the blending amount thereof is preferably 0.001 to 5.0 W / V%, more preferably 0.001 to 1 W / V%, and 0.001 to 0.1 W / V% in the composition. Is even more preferable.

Drugs (pharmaceutically active ingredients) include, for example, decontamination components (eg, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, nafazoline hydrochloride, nafazoline nitrate, phenilefurin hydrochloride, dl-methylephedrine hydrochloride, etc.), Anti-inflammatory and astringent agents (eg, neostigmine methyl sulfate, epsilon-aminocaproic acid, allantin, velberin chloride hydrate, velberin sulfate hydrate, sodium azulene sulfonate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate, lysoteam hydrochloride Salts, etc.), antihistamines (eg, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), water-soluble vitamins (flavinadenine dinucleotide sodium, cyanocobalamine, pyridoxin hydrochloride, pantenol, calcium pantothenate, sodium pantothenate, etc.) , Amino acids (for example, potassium L-aspartate, magnesium L-aspartate, potassium-magnesium L-aspartate (equal mixture), aminoethylsulfonic acid, sodium chondroitin sulfate, etc.), sulfa agents and the like. When a drug is blended, an effective appropriate amount of each drug can be selected as the blending amount, but 0.001 to 5 W / V% is preferable in the composition, and 0.001 to 1 W / V% is more. It is preferably 0.001 to 0.1 W / V%, more preferably 0.001 to 0.1 W / V%.

[Production method]
The method for producing the composition of the present invention is not particularly limited, but for example, a mixed solution of an oily component such as component (A) and a surfactant component such as component (B) is mixed with an aqueous solution containing an aqueous component. It can be obtained by emulsifying, adjusting the pH, and then adjusting the total volume with water. The mixing method of each liquid may be a general method, and is appropriately performed using a pulsator, a propeller blade, a paddle blade, a turbine blade, etc., but the rotation speed is not particularly limited and should be set so as not to foam violently. Is preferable. The mixing temperature of each liquid is not particularly limited, but it is preferable that both the oily component and the surfactant component are equal to or higher than the melting temperature, and specifically, the mixture is appropriately selected from the range of 40 to 95 ° C.

Further, the obtained composition may be filled in a resin container, further sealed with a package, and an inert gas such as nitrogen may be sealed in the space formed between the container and the package. After filling the composition in a resin container, it may be sealed with a package together with an oxygen scavenger.

[Ophthalmic composition]
The composition of the present invention is an "aqueous ophthalmic composition". In the present invention, the "aqueous ophthalmic composition" refers to an ophthalmic composition in which the medium is water. The amount of water to be blended is preferably 90.0 to 99.5 W / V% in the composition, preferably 95, from the viewpoint of facilitating mixing with the tear fluid and facilitating the transfer of the component (A) to the tear fluid. .0-98.0 W / V% is more preferable.

The composition of the present invention is preferably a liquid from the viewpoint of facilitating adaptation to the eyes, and the viscosity at 25 ° C. is 20 mPa · s or less from the viewpoint of facilitating mixing with tears and improving (A) component release. Is preferable, 10 mPa · s or less is more preferable, 5 mPa · s or less is further preferable, and 2 mPa · s or less is particularly preferable. The viscosity is measured using a cone plate type viscometer (DV2T, Eiko Seiki Co., Ltd.).

The composition of the present invention is preferably clearer from the viewpoint of facilitating detection when a foreign substance is mixed. The transmittance of the composition, specifically, the transmittance at a wavelength of 600 nm measured using a spectrophotometer (UV-1800, Shimadzu Corporation) is 60% or more, preferably 70 to 100%, and 75 to 75 to 100%. 100% is more preferable, and 90 to 100% is further preferable. The measurement temperature is room temperature.

The particle size of the emulsion particles (aggregate of the components (A) and (B)) contained in the composition of the present invention may be 800 nm or less, but is preferably 500 nm or less, more preferably 300 nm or less. .. The lower limit is not particularly limited, but it may be 1 nm. In the present invention, the particle size refers to the average diameter (median diameter nm) of the volume-based particle size distribution calculated from the scattered light intensity. The particle size is measured by using various measuring devices that apply principles such as light scattering, using a constant temperature bath, and under constant temperature conditions of 25 ° C. As such an apparatus, for example, a particle size measuring apparatus (ELSZ-200ZS, manufactured by Otsuka Electronics Co., Ltd.) can be used for measurement.

The composition of the present invention can be suitably used as an eye drop, an eye drop for contact lenses, an eye wash, etc., but the tear solution dilution ratio is high, and the withdrawal of the surfactant from the component (A) is further promoted. In particular, eye drops and eye drops for contact lenses (eye drops for contact lens wearers) from the viewpoint that the release property of the component A) from the composition is improved and the component (A) is efficiently supplied to the tear oil layer. It can be suitably used as an eye drop such as (agent). The contact lens is not particularly limited, such as a hard contact lens, a soft contact lens, a silicon hydrogel soft contact lens, an O ₂ hard contact lens, and a color contact lens.

When used as an eye drop or an eye drop for contact lenses, it is preferable to instill 10 to 100 μL of 1 to 3 drops at a time, 1 to 6 times a day, and the release property of the component (A) by overflowing from the eyes. 10 to 50 μL at a time, 1 to 6 drops per day, more preferably 1 to 6 times per day, and 10 to 30 μL at a time, 1 to 3 drops per day, 1 to 6 times per day. .. When used as an eye wash, it is preferable to wash the eyes 3 to 6 mL at a time and 3 to 6 times a day.

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. Unless otherwise specified in the following example, g / 100 mL is W / V%, and the ratio indicates a mass ratio (the same value as the W / V% ratio).

[Examples, comparative examples]
Each water-soluble component in the table below was dissolved in 90 mL of purified water and heated and mixed at 90 ° C. for 15 minutes. Separately, a premixture of the component (A) and the component (B), and if necessary, the component (C) was prepared and heated and mixed at 90 ° C. for 15 minutes. Next, a predetermined amount of the premix was added to the aqueous solution, and the mixture was further heated and mixed at 90 ° C. for 15 minutes. Then, the mixture was cooled to room temperature, the pH was adjusted with sodium hydroxide, and purified water was added to a concentration of 100 mL. The viscosity of each example was in the range of 0.5 to 2.0 mPa · s. The obtained composition was evaluated as follows. The results are also shown in the table.

[Measurement of transmittance (%) of composition]
The transmittance (%) at a wavelength of 600 nm was measured using a plastic cell using an ultraviolet-visible near-infrared spectrophotometer UV-1800 (Shimadzu Corporation) for the composition immediately after production. The results are shown by the following evaluation criteria. ●, ○ and ◎ are passed.
⊚: 90% or more ○: 70% or more and less than 90% ●: 60% or more and less than 70% ×: less than 60%

[(A) component release by dilution]
Human tear fluid is said to have an average of 7 μL, and when 30 to 60 μL of eye drops are instilled, it is diluted about 1.12 to 1.23 times. In this test, in order to evaluate that the component (A) solubilized by diluting the tear solution of the composition floats at the gas-liquid interface (release), physiological saline was used as a model tear solution. The release of component (A) on the water surface when the composition was diluted at a dilution ratio of about 1.2 times was observed. A volumetric flask with a narrow opening was used to facilitate observation. Specifically, 10 mL of physiological saline was added to a 50 mL volumetric flask, and eye drops were further poured into the opening. A volumetric flask having a dilution ratio of 1.2 times when poured to the opening was used, and the area of the opening was 152 mm ² . To observe the component (A) on the water surface, light is applied to the liquid surface using a fluorescent lamp as a light source, the interference light of the oil floating on the liquid surface is observed, and the ratio of the area of the interference light of the oil to the water surface is calculated. However, it was evaluated according to the following criteria. No oil interference light was observed in any of the examples and comparative examples in the case of undiluted oil. ●, ○ and ◎ are passed.
[Evaluation criteria]
⊚: Oil interference light is observed and occupies the entire surface of the volumetric flask opening ○: Oil interference light is observed and does not cover the entire surface of the volumetric flask opening, but it is 50% or more ●: Oil interference light is observed, and the proportion of the volumetric flask opening is less than 50%. ×: No oil interference light is observed.

The raw materials used in the above example are shown below. Unless otherwise specified, the amount of each component in the table is a net conversion amount.
Purified lanolin (Japanese Pharmacopoeia purified lanolin, manufactured by Kenei Pharmaceutical Co., Ltd.)
Polyoxyethylene hydrogenated castor oil (manufactured by Nippon Surfactant Industry Co., Ltd.)
・ NIKKOL HCO-20 (medicinal)
・ NIKKOL HCO-30 (medicinal)
・ NIKKOL HCO-40 (medicinal)
・ NIKKOL HCO-50 (medicinal)
・ NIKKOL HCO-60 (medicinal)
Polyoxyethylene castor oil 35: Average number of moles of ethylene oxide added 35 (Uniox C35, manufactured by NOF CORPORATION)
Polyethylene glycol monostearate: Average number of moles of ethylene oxide added 10 (MYS10V, manufactured by Nippon Surfactant Industry Co., Ltd.)
Polyoxyethylene (20) sorbitan oleate: Polysorbate 80 (Polysorbate 80, manufactured by Kao Corporation)
Boric acid (manufactured by Kanto Chemical Co., Inc.)
Torometa Mall (manufactured by Kanto Chemical Co., Inc.)
Sodium edetate dihydrate: Clewat N, manufactured by Nagase ChemteX Corporation
Sodium chloride (manufactured by Tomita Pharmaceutical Co., Ltd.)
Sodium hydroxide (manufactured by Wako Pure Chemical Industries, Ltd.)
Retinol palmitate ester (retinol palmitate ester, 174 units / g, manufactured by DSM Co., Ltd.)
d-α-tocopherol acetate (RIKEN E acetate α, manufactured by RIKEN Vitamin Co., Ltd.)

Claims (6)

An aqueous ophthalmic composition containing (A) one or more selected from wax esters and sterol esters, and (B) polyoxyethylene hydrogenated castor oil having an average addition molar number of ethylene oxide chains of 30 to 40. The compounding mass ratio of the component (A) and the component (B) is (7.5-0.15 × N) ≦ (B) / (A) ≦ when the average number of added moles of the component (B) is N. The aqueous ophthalmic composition according to claim 1, which satisfies (17.5-0.25 × N). The component (B) is polyoxyethylene hydrogenated castor oil having an average addition molar number of ethylene oxide chains of 30, and the compounding mass ratio of the components (A) and (B) is 3 ≦ (B) / (A). The aqueous ophthalmic composition according to claim 2, wherein the composition is ≦ 10. The component (B) is polyoxyethylene hydrogenated castor oil having an average addition molar number of ethylene oxide chains of 40, and the compounding mass ratio of the components (A) and (B) is 1.5 ≦ (B) / (. A) The aqueous ophthalmic composition according to claim 2, wherein ≦ 7.5. The aqueous ophthalmic composition according to any one of claims 1 to 4, wherein the component (A) is lanolin. (C) The aqueous ophthalmic composition according to any one of claims 1 to 5, which contains at least one selected from vitamin A and vitamin E.