JP2022056765A - Ophthalmic composition for improving eye fatigue - Google Patents

Abstract

To provide an ophthalmic composition that can sufficiently improve eye fatigue.SOLUTION: An ophthalmic composition for improving eye fatigue has an osmotic pressure of 220-260 mOsm. The ophthalmic composition preferably contains terpenoid. The ophthalmic composition is suitable for contact lenses.SELECTED DRAWING: None

Description

The present invention relates to an ophthalmic composition for improving eye strain.

In recent years, an increasing number of people have complained of eye strain due to changes in their lifestyles. Causes of eye strain include VDT (Visual Display Thermals) work, which has been rapidly increasing with the spread of personal computers and smartphones.
In addition to eye strain, wearing contact lenses promotes various problems such as dry eyes, itching, and redness. In particular, they often complain of dry eyes (dry eye symptoms) and tiredness caused by wearing soft contact lenses for a long time.

Therefore, an ophthalmic composition has been proposed that improves the dryness of the eyes caused by wearing soft contact lenses.
For example, Patent Document 1 discloses an ophthalmic composition for soft contact lenses containing fat-soluble vitamins.

Japanese Unexamined Patent Publication No. 2001-158734

However, the ophthalmic composition described in Patent Document 1 cannot sufficiently improve eye strain.
An object of the present invention is to provide an ophthalmic composition capable of sufficiently improving eye strain.

The present invention has the following aspects.
[1] An ophthalmic composition for improving eye strain having an osmotic pressure of 220 to 260 mOsm.
[2] The ophthalmic composition for improving eye strain according to the above [1], which comprises a terpenoid.
[3] Selected from the group consisting of buffers, edetic acids, edetates, decongestants, astringents, anti-inflammatory agents, antihistamines, vitamins, amino acids, water-soluble polymer compounds, and nonionic surfactants. The ophthalmic composition for improving eye fatigue according to the above [1] or [2], further comprising at least one component.
[4] The ophthalmic composition for improving eye strain according to any one of the above [1] to [3], further comprising an osmotic pressure adjusting agent.
[5] An ophthalmic composition for improving eye strain according to any one of the above [1] to [4], which is for contact lenses.

According to the present invention, it is possible to provide an ophthalmic composition capable of sufficiently improving eye strain.

Hereinafter, the present invention will be described in detail.
In the present invention, the term "ophthalmic composition" refers to eye drops (synonymous with eye drops or eye drops), eye drops for contact lenses, artificial tears, eye wash (synonymous with eye wash or eye drops), and contacts. Shown are all ophthalmic compositions such as lens wearers or contact lens care products (including disinfectants, preservatives, cleaning agents, etc.), eye drops and the like.
Further, in the present invention, "water-soluble" means that the solubility in 1 L of water at 25 ° C. is 0.1 g or more.
Further, in the present invention, the "polymer compound" is a compound having a mass average molecular weight of 1000 or more. The mass average molecular weight is a value measured by GPC (gel permeation chromatography) using an eluent such as THF (tetrahydrofuran) and converted based on a calibration curve in a standard sample such as PEG (polyethylene glycol). ..
Further, in the present specification, "w / v%", which is a unit of the content (concentration) of each component, means "mass / volume%", and the mass of the compounding component contained in 100 mL of the ophthalmic composition. It represents (g) and is synonymous with "g / 100 mL". The content of each component shown below is a preferable range when blended in an ophthalmic composition, and is an amount in the ophthalmic composition.

[Osmotic pressure]
The osmotic pressure of the ophthalmic composition for improving eye strain of the present invention (hereinafter, also simply referred to as “ophthalmic composition”) is 220 to 260 mOsm, preferably 240 to 260 mOsm. When the osmotic pressure of the ophthalmic composition is within the above range, an excellent eye strain improving effect can be obtained. In addition, the use of ophthalmic compositions when or during wearing contact lenses provides an excellent refreshing sensation. In particular, when an ophthalmic composition is used when or during wearing a soft contact lens, the refreshing sensation is more easily felt and the sustainability of the refreshing sensation is enhanced. When the osmotic pressure of the ophthalmic composition is equal to or higher than the above lower limit value, discomfort is less likely to occur at the time of instillation. When the osmotic pressure of the ophthalmic composition is not more than the above upper limit value, an excellent eye strain improving effect and a long-lasting refreshing sensation can be obtained.
The osmotic pressure of the ophthalmic composition shall be in accordance with the method specified in "2.47 Osmotic pressure measurement method (osmolal concentration measurement method)" of "General test method" described in the 17th revised Japanese Pharmacopoeia. It is a value measured at 25 ° C.

The osmotic pressure of the ophthalmic composition can be adjusted by the type and content of the compounding components contained in the ophthalmic composition. It can be easily adjusted depending on the content.

[Ingredients]
The ophthalmic composition of the present invention may contain various components in order to satisfy the above-mentioned osmotic pressure.
Hereinafter, an example of the compounding components of the ophthalmic composition will be described.

<Osmotic pressure regulator>
The osmotic pressure regulator is a component that regulates the osmotic pressure of an ophthalmic composition.
Examples of the osmotic pressure adjusting agent include alkali metal salts, alkaline earth metal salts, polyhydric alcohols, sugars and the like.
Specific examples of the alkali metal salt include chlorides of alkali metals such as sodium chloride and potassium chloride; organic acid alkali metal salts such as sodium acetate and potassium acetate; borosand, sodium hydrogen sulfite, sodium hydrogen carbonate and sodium carbonate. , Inorganic acid alkali metal salts such as disodium hydrogen phosphate and sodium dihydrogen phosphate.
Specific examples of the alkaline earth metal salt include chlorides of alkaline earth metals such as calcium chloride and magnesium chloride.
Specific examples of the polyhydric alcohol include glycerin, propylene glycol, butylene glycol, polyethylene glycol and the like.
Specific examples of the saccharide include sorbitol, glucose, mannitol, xylitol and the like.
These osmotic pressure regulators may be in the form of solvates such as hydrates.
Among these, as the osmotic pressure adjusting agent, sodium chloride, potassium chloride, glycerin, propylene glycol and polyethylene glycol are preferable.
These osmotic pressure adjusting agents may be used alone or in combination of two or more.

The content of the osmotic pressure adjusting agent may be appropriately set so as to satisfy the above-mentioned osmotic pressure according to the type of the osmotic pressure adjusting agent, the type and content of other components to be blended, and the like. .001 to 5 w / v% is preferable, and 0.005 to 3 w / v% is more preferable.

<Terpenoid>
Terpenoids are components (cooling agents) that give a refreshing sensation.
Examples of terpenoids include menthol, camphor, borneol, geraniol, cineole, linalool and the like.
These terpenoids may be d-form, l-form, or dl-form.
Among these, as the terpenoid, menthol is preferable, and l-menthol is more preferable.
These terpenoids may be used alone or in combination of two or more.

The content of the terpenoid is preferably 0.001 to 0.1 w / v%, more preferably 0.002 to 0.05 w / v%, still more preferably 0.003 to 0.03 w / v%.

<Buffering agent>
The buffering agent is a component that regulates the osmotic pressure of the ophthalmic composition and imparts a buffering action.
The buffer is not particularly limited as long as it is pharmaceutically acceptable, but for example, a borate buffer, a Tris buffer, a citrate buffer, a phosphate buffer, a tartrate buffer, an acetate buffer, and a carbon dioxide buffer. Agents, amino acid buffers and the like.
Specific examples of the boric acid buffer include boric acid or a salt thereof. The borate is not particularly limited as long as it is pharmaceutically acceptable, but for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; ammonium salt; triethylamine. , Organic amine salts such as triethanolamine and the like. Examples of the borate include borax.
Specific examples of the Tris buffer include tromethamole (also known as tris (hydroxymethyl) aminomethane) or a salt thereof. The tromethamole salt is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include organic acid salts such as acetate; and inorganic acid salts such as hydrochloride and sulfonate. Examples of the tromethamole salt include tromethamole hydrochloride and the like.
Specific examples of the citric acid buffer include citric acid or a salt thereof. The citrate is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as calcium salt and magnesium salt. Examples of the citrate include sodium citrate and the like.
Specific examples of the phosphoric acid buffer include phosphoric acid or a salt thereof. The phosphate is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salts and potassium salts. Examples of the phosphate include sodium hydrogen phosphate and sodium dihydrogen phosphate.
Specific examples of the tartaric acid buffer include tartaric acid or a salt thereof, gluconic acid or a salt thereof, and the like. The tartrate and gluconate are not particularly limited as long as they are pharmaceutically acceptable, but for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt and the like. Can be mentioned. Examples of the tartrate salt include sodium tartrate and the like. Examples of the gluconate include sodium gluconate and the like.
Specific examples of the acetic acid buffer include acetic acid or a salt thereof, glacial acetic acid and the like. The acetate is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; and ammonium salts. Be done. Examples of the acetate include sodium acetate and the like.
Specific examples of the carbonic acid buffer include carbonic acid or a salt thereof. The carbonate is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as calcium salt and magnesium salt. Examples of the carbonate include sodium carbonate, sodium hydrogencarbonate and the like.
Specific examples of the amino acid buffer include various amino acids such as epsilon-aminocaproic acid, potassium aspartate, aminoethylsulfonic acid, glutamic acid, and sodium glutamate, or salts thereof. The amino acid salt is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salt and potassium salt.
These buffers may be in the form of solvates such as hydrates.
Among these, boric acid, borate, trometamol, and trometamol salt are preferable as the buffering agent from the viewpoint of enhancing the antiseptic power, and a combination of boric acid and trometamol is more preferable.
These buffers may be used alone or in combination of two or more.

The content of the buffer is preferably 0.001 to 5 w / v%, more preferably 0.003 to 3 w / v%, still more preferably 0.005 to 2.5 w / v%.

<Edetoic acid and its salts>
Edetoic acid (also known as ethylenediaminetetraacetic acid) and a salt thereof are components formulated for the purpose of imparting a stabilizing effect to the components in the composition. In addition, the antiseptic power can be enhanced.
The edetate is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as calcium salt and magnesium salt. Examples of the edetate include sodium edetate and the like.
Edetonic acid and its salts may be in the form of solvates such as hydrates, respectively.
Among these, as edetic acid and its salt, sodium edetate and sodium edetate hydrate are preferable, and sodium edetate is more preferable.
These edetic acids and salts thereof may be used alone or in combination of two or more.

The content of edetic acid and its salt is preferably 0.001 to 0.2 w / v%, more preferably 0.003 to 0.15 w / v%, still more preferably 0.005 to 0.1 w / v%. ..

<Decongestant>
Examples of the decongestant (vasoconstrictor) include epinephrine, epinephrine hydrochloride, methylnorepinephrine, norepinephrine, ephedrine, methylephedrine, pseudoephedrine, ephedrine hydrochloride, tetrahydrozoline hydrochloride, nafazoline nitrate, phenyleffrin hydrochloride, dl-methylephedrine hydrochloride. , Oxymethazoline, methoxamine, phenylpropanoramine, ephedrine, middrine, tramazoline, cinefurin, silazoline, xylomezoline, and pharmaceutically acceptable salts thereof (eg, alkali metal salts such as sodium salt, potassium salt; calcium salt, Alkaline earth metal salts such as magnesium salts, etc.) and the like.
These decongestants may be used alone or in combination of two or more.

The content of the decongestant is preferably 0.001 to 1 w / v%, more preferably 0.003 to 0.5 w / v%, and even more preferably 0.005 to 0.2 w / v%.

<Astringent>
Examples of the astringent include neostigmine methyl sulfate, zinc sulfate, zinc lactate and the like. Neostigmine methyl sulfate has an eye muscle regulating action on ciliary muscles and the like.
These astringents may be used alone or in combination of two or more.

The content of the astringent is preferably 0.0001 to 0.1 w / v%, more preferably 0.0003 to 0.05 w / v%, and even more preferably 0.0005 to 0.01 w / v%.

<Anti-inflammatory agent>
Examples of the anti-inflammatory agent include epsilon-aminocaproic acid, allantin, velverin chloride hydrate, velverin sulfate hydrate, sodium azulene sulfonate, dipotassium glycyrrhizinate, lysoteam hydrochloride, planoprofen and the like.
These anti-inflammatory agents may be used alone or in combination of two or more.

The content of the anti-inflammatory agent is preferably 0.001 to 10 w / v%, more preferably 0.003 to 8 w / v%, and even more preferably 0.005 to 5 w / v%.

<Antihistamine>
Examples of the antihistamine include diphenhydramine hydrochloride, chlorpheniramine maleate, ketotifen fumarate, olopatadine hydrochloride and the like.
These antihistamines may be used alone or in combination of two or more.

The content of the antihistamine is preferably 0.001 to 0.1 w / v%, more preferably 0.003 to 0.08 w / v%, and even more preferably 0.005 to 0.05 w / v%.

<Vitamins>
Examples of vitamins include water-soluble vitamins such as vitamin B and vitamin C; and fat-soluble vitamins such as vitamin A and vitamin E.
Specific examples of vitamin B include flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, and sodium pantothenate.
Specific examples of vitamin C include sodium ascorbate and the like.
Specific examples of the vitamin A include retinol palmitate (retinyl palmitate ester) and retinyl acetate.
Specific examples of vitamin E include tocopherol acetate, tocopherol succinate, and tocopherol nicotinate.
These vitamins may be used alone or in combination of two or more.

The content of vitamins is preferably 0.001 to 1 w / v%, more preferably 0.003 to 0.5 w / v%, and even more preferably 0.005 to 0.1 w / v%.
When the vitamins are vitamin A, the content of vitamin A is preferably 1000 units / 100 mL or more, more preferably 3000 units / 100 mL or more, further preferably 5000 to 100,000 units / 100 mL, and 10,000 to 8.0. 10,000 units / 100 mL is particularly preferable, and 50,000 to 65,000 units / 100 mL is most preferable. In addition, 1 unit in the content of vitamin A means 1 unit of vitamin A described in the 17th revised Japanese Pharmacopoeia Vitamin A quantification method.

<Amino acid>
Examples of the amino acid include potassium L-aspartate, magnesium L-aspartate, potassium-magnesium L-aspartate (equal mixture), aminoethylsulfonic acid, sodium chondroitin sulfate and the like.
These amino acids may be used alone or in combination of two or more.

The amino acid content is preferably 0.001 to 5 w / v%, more preferably 0.003 to 3 w / v%, and even more preferably 0.005 to 1 w / v%.

<Water-soluble polymer compound>
Examples of the water-soluble polymer compound include polyvinylpyrrolidone, hydroxyethyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, dextran, alginic acid, and sodium alginate. Examples include xanthan gum.
These water-soluble polymer compounds may be used alone or in combination of two or more.

The content of the water-soluble polymer compound is not particularly limited as long as it does not impair the usability such as stickiness and blurring, but is preferably 0.001 to 5 w / v%, preferably 0.003 to 3 w / v, for example. % Is more preferable, and 0.005 to 1 w / v% is even more preferable.

<Nonionic surfactant>
The nonionic surfactant is a component used as a solubilizer for oily components (for example, terpenoids, fat-soluble vitamins, etc.) to enhance the compounding stability of the oily components.
The nonionic surfactant is not particularly limited, and a nonionic surfactant used in an ophthalmic composition can be used. Specifically, polyoxyethylene glycol oil, polyoxyethylene hydrogenated surfactant, and polyoxy can be used. Examples thereof include ethylene sorbitan fatty acid ester and nonionic surfactants (other nonionic surfactants) other than the above.
These nonionic surfactants may be used alone or in combination of two or more.

Polyoxyethylene castor oil (POE castor oil) is a compound obtained by addition polymerization of ethylene oxide (EO) to castor oil, and several types with different average number of moles of ethylene oxide are known. .. The average number of moles of ethylene oxide added to the polyoxyethylene castor oil is not particularly limited, but is preferably 3 to 60 mol.
Specific examples of the polyoxyethylene castor oil include polyoxyethylene castor oil 3 (EO average number of moles added 3), polyoxyethylene castor oil 10 (EO average number of moles added 10), and polyoxyethylene castor oil 20 (EO average number of moles added 10). EO average addition mole number 20), polyoxyethylene castor oil 35 (EO average addition mole number 35), polyoxyethylene castor oil 40 (EO average addition mole number 40), polyoxyethylene castor oil 50 (EO average addition mole number 50) 50), polyoxyethylene castor oil 60 (EO average number of added moles 60) and the like.
Among these, from the viewpoint of reducing the irritation sensation at the time of instillation, the polyoxyethylene castor oil 35 is preferable, and the one conforming to the pharmaceutical additive standard 2003 is more preferable.
These polyoxyethylene castor oils may be used alone or in combination of two or more.

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 number of moles of ethylene oxide are known. ing. The average number of moles of ethylene oxide added to the polyoxyethylene hydrogenated castor oil is not particularly limited, but is preferably 5 to 100 mol.
Specific examples of the polyoxyethylene cured castor oil include polyoxyethylene cured castor oil 5 (EO average number of added moles 5), polyoxyethylene cured castor oil 10 (EO average number of added moles 10), and polyoxyethylene cured. Himashima oil 20 (EO average number of added moles 20), polyoxyethylene cured Himashima oil 30 (EO average number of added moles 30), polyoxyethylene cured Himashima oil 40 (EO average number of added moles 40), polyoxyethylene cured Himashima oil 50 (EO average addition mole number 50), polyoxyethylene cured castor oil 60 (EO average addition mole number 60), polyoxyethylene cured castor oil 80 (EO average addition mole number 80), polyoxyethylene cured castor oil 100 (EO average addition mole number 80) EO average number of added moles 100) and the like.
Among these, from the viewpoint of reducing the irritation feeling at the time of instillation, the polyoxyethylene hydrogenated castor oil 40 and the polyoxyethylene hydrogenated castor oil 60 are preferable as the polyoxyethylene hydrogenated castor oil, and the standard of the pharmaceutical additive standard 2003 is met. A compatible one is more preferable.
Examples of the commercially available product of the polyoxyethylene hydrogenated castor oil include the trade name “HCO-60” manufactured by Nippon Surfartant Industry Co., Ltd. as a commercially available product of the polyoxyethylene hydrogenated castor oil 60.
These polyoxyethylene hydrogenated castor oils may be used alone or in combination of two or more.

Examples of the polyoxyethylene sorbitan fatty acid ester include monolaurate polyoxyethylene (20) sorbitan (polysorbate 20), monopalmitate polyoxyethylene (20) sorbitan (polysorbate 40), and monostearate polyoxyethylene (20) sorbitan (20). Examples thereof include polysorbate 60), polyoxyethylene tristearate (20) sorbitan (polysorbate 65), polyoxyethylene monooleate (20) sorbitan (polysorbate 80), and the like.
Among these, as the polyoxyethylene sorbitan fatty acid ester, monooleic acid polyoxyethylene (20) sorbitan (polysorbate 80) is preferable.
Examples of the commercially available product of the polyoxyethylene sorbitan fatty acid ester include the trade name “Leodor TW-O120V” manufactured by Kao Corporation as a commercially available product of the polysorbate 80.
These polyoxyethylene sorbitan fatty acid esters may be used alone or in combination of two or more.

Examples of other nonionic surfactants include polyoxyethylene polyoxypropylene glycol (POEPOP glycol) typified by Poroxumer, polyethylene glycol monostearate (10), and polyethylene glycol monostearate (40). Examples thereof include polyethylene glycol stearate.
These other nonionic surfactants may be used alone or in combination of two or more.

The content of the nonionic surfactant is preferably 0.0001 to 10 w / v%, more preferably 0.0001 to 5 w / v%.
When polyoxyethylene castor oil is contained as a nonionic surfactant, the content thereof is preferably 0.003 to 10 w / v%, more preferably 0.003 to 5 w / v%, and 0.03 to 1 w / v. % Is more preferable.
When polyoxyethylene hydrogenated castor oil is contained as a nonionic surfactant, the content thereof is preferably 0.003 to 10 w / v%, more preferably 0.003 to 5 w / v%, and 0.03 to 1 w / v. v% is more preferred.

<Other ingredients>
The ophthalmic composition of the present invention may contain an appropriate amount of other components other than the above-mentioned components as long as the effects of the present invention are not impaired.
Other components include, for example, antibacterial components, local anesthetics or soothing agents, pH regulators, stabilizers, other oily components, preservatives, other inorganic compounds and the like.
These other components may be used alone or in combination of two or more.

(Antibacterial ingredient)
Examples of the antibacterial component include sulfa agents such as sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, and sulfisomidin sodium.
These antibacterial components may be used alone or in combination of two or more.
The content of the antibacterial component is preferably 0.001 to 5 w / v%, more preferably 0.001 to 3 w / v%, and even more preferably 0.001 to 1 w / v%.

(Local anesthetic or painless agent)
Examples of the local anesthetic or pain-relieving agent include chlorobutanol, oxybuprocaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, piperokine hydrochloride, procaine hydrochloride, proparakine hydrochloride, hexthiocaine hydrochloride, lidocaine hydrochloride and the like.
These local anesthetics or soothing agents may be used alone or in combination of two or more.
The content of the local anesthetic or pain-relieving agent is preferably 0.001 to 5 w / v%, more preferably 0.001 to 3 w / v%, and even more preferably 0.001 to 1 w / v%.

(PH regulator)
Examples of the pH adjusting agent include an inorganic acid, an inorganic alkaline agent, and an organic alkaline agent.
Specific examples of the inorganic acid include (dilute) hydrochloric acid.
Specific examples of the inorganic alkaline agent include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogencarbonate and the like.
Specific examples of the organic alkaline agent include monoethanolamine and diethanolamine.
These pH adjusters may be used alone or in combination of two or more.

(Stabilizer)
Examples of the stabilizer include a fat-soluble antioxidant and a water-soluble antioxidant.
Specific examples of the fat-soluble antioxidant include cyclodextrin, monoethanolamine, dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), and vitamin E (for example, tocopherol acetate, tocopherol nicotinate, and tocopherol succinate). Etc.), vitamin A (for example, retinol palmitate, retinol acetate, etc.) and the like.
Specific examples of the water-soluble antioxidant include sodium sulfite, potassium sulfite, dried sodium sulfite (anhydrous sodium sulfite), sodium pyrosulfite, potassium pyrosulfite, sodium hydrogen sulfite, potassium hydrogen sulfite and other sulfites; ascorbin. Acid; Sodium ascorbate and the like can be mentioned.
In addition, vitamin E and vitamin A may be used as the vitamins described above, or may be used as a stabilizer.
Further, when the stabilizer is blended in an ophthalmic composition for contact lens wearers, the stabilizer preferably has low lens adsorptivity and accumulation. Specific examples of such stabilizers include cyclodextrin, vitamin E, vitamin A, sulfite (for example, sodium sulfite, potassium sulfite, dry sodium sulfite (anhydrous sodium sulfite), sodium pyrosulfite, potassium pyrosulfite, etc.). (Sodium hydrogen sulfite, potassium hydrogen sulfite, etc.), ascorbic acid, sodium ascorbate, etc. may be mentioned.
These stabilizers may be used alone or in combination of two or more.
The content of the stabilizer is preferably 0.001 to 5 w / v%, more preferably 0.001 to 1 w / v%, still more preferably 0.001 to 0.1 w / v%.

(Other oily ingredients)
Examples of other oily components include soybean oil, olive oil, corn oil, coconut oil, almond oil, medium-chain fatty acid triglyceride, liquid paraffin, white vaseline, refined lanolin, cholesterol and the like.
These other oily components may be used alone or in combination of two or more.
The content of other oily components is preferably 0.001 to 1 w / v%, more preferably 0.001 to 0.5 w / v%, and even more preferably 0.001 to 0.25 w / v%.

(Preservative)
Examples of the preservative include benzalkonium chloride, benzethonium chloride, thimerosal, phenylethyl alcohol, alkylpolyaminoethylglycine, alkyldiaminoethylglycine or a salt thereof (for example, alkyldiaminoethylglycine hydrochloride, etc.), chlorhexidine gluconic acid, methyl paraoshiki benzoate. , Ethyl paraoxybenzoate, ethylpropyl paraoxybenzoate, sodium benzoate, sorbic acid, chlorobutanol, oxyquinoline sulfate, benzyl alcohol, polyhexamethylene biguanide, polydronium chloride and the like.
These preservatives may be used alone or in combination of two or more.
The content of the preservative can be 0.0001 to 0.5 w / v%, preferably 0.1 w / v% or less, more preferably 0.01 w / v% or less, and 0.001 w / v. % Or less is more preferable, and 0.0001 w / v% or less is particularly preferable.
If the patient has dry eye or dry eye symptoms, and for the prevention thereof, it is preferable that the ophthalmic composition contains substantially no preservative. Here, "substantially free" means that preservatives are not positively blended except for those that are unintentionally contained.

(Other inorganic compounds)
Examples of other inorganic compounds include sodium thiosulfate, titanium oxide, zinc chloride and the like.
These other inorganic compounds may be used alone or in combination of two or more.
The content of other inorganic compounds is preferably 0.001 to 5 w / v%, more preferably 0.001 to 3 w / v%, still more preferably 0.001 to 1 w / v%.

[PH]
The pH of the ophthalmic composition of the present invention at 25 ° C. is preferably 3.5 to 13.0. In particular, from the viewpoint of further improving eye strain, 3.5 to 8.0 is more preferable, and 5.5 to 8.0 is even more preferable.
The pH of the ophthalmic composition is a value measured at 25 ° C. using a pH meter.

[viscosity]
The viscosity of the ophthalmic composition of the present invention at 25 ° C. is preferably 1.1 to 50 mPa · s, more preferably 1.1 to 40, still more preferably 1.1 to 30, still more preferably 1.1 to 20. , 1.1 to 15, more preferably 1.1 to 12, particularly preferably 1.1 to 10, and most preferably 1.1 to 8.
The viscosity of the ophthalmic composition is the "single cylindrical rotational viscosity" of the "second method rotational viscometer method" in the "viscosity measurement method" of the "general test method" described in the 17th revised Japanese Pharmacy. It is a value measured at 25 ° C. using a B-type rotational viscometer according to the method specified in "Meter (Brookfield type viscometer)". Conditions such as the rotor and rotation speed used for measurement are selected according to the viscosity range. Examples of the B-type rotational viscometer include a cone plate type viscometer.

[Dosage form]
The ophthalmic composition of the present invention is preferably an aqueous ophthalmic composition.
Here, the "aqueous ophthalmic composition" refers to an ophthalmic composition in which the medium is water. That is, the ophthalmic composition of the present invention is preferably liquid.
The water used in the ophthalmic composition is not particularly limited as long as it is pharmaceutically, pharmacologically or physiologically acceptable, and for example, distilled water, normal water, purified water, sterile purified water, and injection water. , Distilled water for injection and the like.
The water content is preferably 90.0 to 99.5 w / v%, more preferably 95.0 to 98.0 w / v%.

The dosage form of the ophthalmic composition of the present invention is not particularly limited, and for example, eye drops (including eye drops that can be instilled while wearing contact lenses), artificial tears, and eye wash (eye washable while wearing contact lenses). It can be suitably used as eye drops), contact lens wearing liquids, contact lens removing liquids, contact lens care products (including disinfectants, preservatives, cleaning agents, etc.). In particular, it can be suitably used as an eye drop or a contact lens wearing solution, and an eye drop is particularly preferable.

The contact lens is not particularly limited, and examples thereof include hard contact lenses (including O ₂ hard contact lenses), soft contact lenses (including both ionic and nonionic), silicone hydrogel contact lenses, and color contact lenses. Can be mentioned. When the ophthalmic composition is substantially free of preservatives, it is particularly suitable for soft contact lenses and silicone hydrogel contact lenses.
In the present invention, an ophthalmic composition used when or while wearing a contact lens (for example, an ophthalmic agent that can be instilled while wearing a contact lens, an eye wash that can be washed while wearing a contact lens, a contact lens wearing liquid). Etc.), contact lens remover, and contact lens care products are also collectively referred to as "ophthalmic compositions for contact lenses." Among them, the ophthalmic composition used by the wearer of soft contact lenses is also referred to as "ophthalmic composition for soft contact lenses".

[Dose, usage]
When the ophthalmic composition of the present invention is an eye drop (including an eye drop that can be instilled while wearing contact lenses), 1 to 3 drops of 5 to 100 μL at a time should be instilled 1 to 6 times a day. It is preferable to instill 1 to 3 drops of 10 to 50 μL at a time, more preferably 1 to 6 drops of 10 to 30 μL per day, and 1 to 6 drops of 10 to 30 μL per day. Is even more preferable.
When the ophthalmic composition of the present invention is an eye wash (including an eye wash that can be washed while wearing contact lenses), it is preferable to use 1 to 20 mL at a time, more preferably 1 to 10 mL, and further. It is preferably 3 to 6 mL. In addition, it is preferable to wash the eyes 1 to 6 times a day, and more preferably 3 to 6 times.
When the ophthalmic composition of the present invention is a contact lens mounting solution, it is preferable to drop 1 to 3 drops on the contact lens at a time, and more preferably 1 to 2 drops.

[Production method]
The ophthalmic composition of the present invention can be obtained by mixing each component contained in the ophthalmic composition. When the ophthalmic composition is an aqueous ophthalmic composition, a component other than the pH adjuster is added to a part of water, the pH is adjusted with a pH adjuster as necessary, and then the total volume of the ophthalmic composition is reached. Is obtained by adjusting with the remaining water.
When producing an ophthalmic composition containing an oily component such as a fat-soluble vitamin (however, excluding terpenoids), the oily component and a solubilizer are first mixed to prepare a mixture A. As the solubilizer, a nonionic surfactant is preferable. Separately, an aqueous component other than a pH adjuster is added to a part of water to prepare an aqueous solution B. Then, the mixture A and the aqueous solution B are mixed and emulsified, the pH is adjusted with a pH adjuster if necessary, and then the total volume of the ophthalmic composition is adjusted with the remaining water to prepare the ophthalmic composition. To get.
When producing an ophthalmic composition containing a terpenoid, the terpenoid and a solubilizer are mixed to prepare a mixture C. As the solubilizer, at least one of a nonionic surfactant and propylene glycol is preferable. Separately, an aqueous component other than a pH adjuster is added to a part of water to prepare an aqueous solution B. Then, the mixture C and the aqueous solution B are mixed, the pH is adjusted with a pH adjuster if necessary, and then the total volume of the ophthalmic composition is adjusted with the remaining water to obtain an ophthalmic composition.
Propylene glycol may be used as the osmotic pressure adjusting agent described above or as a solubilizing agent.

The mixing method of each component is not particularly limited, and a general method can be used, for example, a pulsator, a propeller blade, a paddle blade, a turbine blade, or the like is appropriately used. The rotation speed is not particularly limited, and it is preferable to set the rotation speed to such that it does not foam violently.
The mixing temperature of each component is not particularly limited, but for example, in the case of producing an ophthalmic composition containing an oily component and a nonionic surfactant, both the oily component and the nonionic surfactant may be above the melting temperature. Preferably, specifically, it is appropriately selected from the range of 40 to 95 ° C.

[Containers, packaging]
The ophthalmic composition of the present invention is provided as a product filled in an arbitrary container.
The container for filling the ophthalmic composition is not particularly limited, and examples thereof include a plastic container and a glass container. Among these, a plastic container is preferable, and specific examples thereof include a container made of a material such as polyethylene, polyethylene terephthalate, polypropylene, polybutylene, polycarbonate, polyarylate, vinyl chloride, or a composite of these materials. Among these materials, polyethylene terephthalate is particularly preferable.
The amount (internal volume) of the ophthalmic composition in the product can be appropriately selected depending on the product and the method of use thereof. For example, when the ophthalmic composition is an eye drop, 2 to 20 mL is preferable, and 5 to 20 mL is preferable. Is more preferable.
The container for filling the ophthalmic composition may be a multi-dose type (multi-unit type) container filled with a plurality of doses of the ophthalmic composition, or may be a single-use unit-dose type container. Among these, a multi-dose type (multi-unit type) container is preferable.

Containers filled with ophthalmic compositions may be fitted with inner plugs or caps. As these inner plugs and caps, the inner plugs and caps made of the materials used for containers of known ophthalmic products can be used.
As the material of the inner plug, polyethylene or polypropylene having a melt flow rate of 2.0 or less, preferably 1.2 to 1.8 is preferable.
As the material of the cap, polyethylene and polypropylene are preferable.

When the ophthalmic composition is filled in a plastic container, water may evaporate from the container during storage and components in the ophthalmic composition may be oxidized. Therefore, it is preferable to fill a plastic container with the ophthalmic composition and then seal the container with a package. At this time, the container may be sealed with a package together with the oxygen scavenger. Further, the space formed between the container and the package may be filled with an inert gas such as nitrogen.
Examples of the package include a pillow film and the like.

[effect]
Since the osmotic pressure of the ophthalmic composition of the present invention described above is 220 to 260 mOsm, eye strain can be sufficiently improved.
Further, when the ophthalmic composition of the present invention is used when or during wearing a contact lens, an excellent refreshing feeling can be obtained. In addition, it also has the effect of improving tears (drying of the eyes), discomfort when wearing hard contact lenses or soft contact lenses, and blurred vision (when there are many eyes and eyes). In particular, when the ophthalmic composition of the present invention is used when or during wearing a soft contact lens, the refreshing sensation is more easily felt and the sustainability of the refreshing sensation is enhanced.

If the ophthalmic composition contains a deconjunctival agent, an anti-inflammatory agent, an anti-histamine agent, vitamins, amino acids, etc., it has an effect of improving conjunctival hyperemia, blepharitis (eyelid soreness), itchy eyes, blurred eyes, etc. It also has the effect of preventing eye diseases, discomfort when wearing contact lenses), and improving eye inflammation (snow eyes, etc.) caused by ultraviolet rays and other rays.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to the following description. The blending amount of the components used in each example is a pure content conversion value unless otherwise specified.

[Examples 1 to 4, Comparative Example 1]
Aqueous components other than purified water and a pH adjuster were dissolved in 90 mL of purified water and stirred and mixed at room temperature (25 ° C.) for 15 minutes so as to have the composition shown in Table 1.
Then, after adjusting the pH of the ophthalmic composition with a pH adjuster as necessary so that the pH at 25 ° C. becomes 7, the remaining purified water is added so that the total volume becomes 100 mL, and the ophthalmic composition is used for ophthalmology. The composition was obtained. As the pH adjuster, at least one of hydrochloric acid and sodium hydroxide was used. A pH meter (manufactured by DKK-TOA CORPORATION, trade name "HM-25R") was used for pH measurement.
The osmotic pressure of the ophthalmic composition was measured as follows. In addition, the effect of improving eye strain was evaluated as follows. These results are shown in Table 1.

[Examples 5 to 8, Comparative Example 2]
Aqueous components other than purified water and a pH adjuster were dissolved in 90 mL of purified water to prepare an aqueous solution B1 so as to have the composition shown in Table 2. A predetermined amount of a mixture of l-menthol and a solubilizer (propylene glycol) prepared separately was added to the aqueous solution B1 and stirred and mixed at room temperature (25 ° C.) for 15 minutes.
Then, after adjusting the pH of the ophthalmic composition with a pH adjuster as necessary so that the pH at 25 ° C. becomes 7, the remaining purified water is added so that the total volume becomes 100 mL, and the ophthalmic composition is used for ophthalmology. The composition was obtained. As the pH adjuster, at least one of hydrochloric acid and sodium hydroxide was used. A pH meter (manufactured by DKK-TOA CORPORATION, trade name "HM-25R") was used for pH measurement.
The osmotic pressure of the ophthalmic composition was measured as follows. In addition, the effect of improving eye strain and the refreshing feeling were evaluated as follows. These results are shown in Table 2.

[Measurement / evaluation]
<Measurement of osmotic pressure>
The osmotic pressure of the ophthalmic composition is automatically permeated according to the method specified in "2.47 Osmotic pressure measurement method (osmol concentration measurement method)" of "General test method" described in the 17th revised Japanese Pharmacy. The measurement was performed at 25 ° C. using an osmometer (manufactured by Advanced Instruments Co., Ltd., trade name “A2O”).

<Evaluation of eye strain improvement effect>
An ophthalmic composition 16 mL was filled in an eye drop container made of polyethylene terephthalate having a capacity of 16 mL. After filling, a polyethylene nozzle (inner plug) was attached to the eye drop container.
As subjects, we selected three office workers who routinely perform VDT work for 4 hours or more a day and feel eye strain. Three subjects each instilled one drop of the ophthalmic composition into each eye, and the degree of eye strain immediately after the instillation and 3 minutes after the instillation was evaluated according to the following evaluation criteria. The average score of the evaluation points of the three subjects was calculated, and the degree of improvement in eye strain was calculated from the following formula (1).
Improvement of eye strain = average score of eye strain 3 minutes after instillation-average score of eye strain immediately after instillation ... (1)
≪Evaluation criteria≫
0 points: I don't feel any eye strain.
1 point: I don't feel much eye strain.
2 points: I feel a little tired of my eyes.
3 points: I feel eyestrain.
4 points: I feel very tired in my eyes.

For Examples 1 to 4, the difference in the degree of eye strain improvement in each Example with respect to the degree of eye strain improvement in Comparative Example 1 was obtained from the following formula (2), and the eye strain improvement was performed according to the following criteria. The effect was evaluated.
For Examples 5 to 8, the difference in the degree of eye strain improvement in each Example with respect to the degree of eye strain improvement in Comparative Example 2 was obtained from the following formula (3), and the eye strain improvement was performed according to the following criteria. The effect was evaluated.
Difference in degree of improvement = degree of improvement in eye strain in Comparative Example 1-degree of improvement in eye strain in Examples ... (2)
Difference in degree of improvement = degree of improvement in eye strain in Comparative Example 2-degree of improvement in eye strain in Examples ... (3)
≪Judgment criteria≫
⊚: The difference in the degree of improvement is 1 point or more.
〇: The difference in the degree of improvement is more than 0 points and less than 1 point.
×: The difference in the degree of improvement is 0 points or less.

<Evaluation of refreshing feeling>
An ophthalmic composition 16 mL was filled in an eye drop container made of polyethylene terephthalate having a capacity of 16 mL. After filling, a polyethylene nozzle (inner plug) was attached to the eye drop container.
As subjects, we selected three office workers who are wearing soft contact lenses who are doing VDT work on a daily basis for 4 hours or more a day and are feeling eye strain. Three subjects instilled one drop of ophthalmic composition into each eye while wearing soft contact lenses, and evaluated the refreshing sensation immediately after instillation and three minutes after instillation according to the following evaluation criteria. The average value of the evaluation points of the names was calculated.
For each immediately after instillation and 3 minutes after instillation, the difference between the average score of the refreshing sensation in Comparative Example 2 and the average score of the refreshing sensation in each example was obtained from the following formula (4), and the refreshing sensation was determined according to the following criteria. I evaluated the feeling.
Difference in average score of refreshing sensation = average score of refreshing sensation in Example-Average score of refreshing sensation in Comparative Example 2 ... (4)
≪Evaluation criteria≫
0 points: I don't feel any refreshing feeling.
1 point: I don't feel a refreshing feeling.
2 points: I feel a little refreshing.
3 points: I feel a refreshing feeling.
4 points: I feel a very refreshing feeling.
≪Judgment criteria≫
◎: The difference in the average score of the refreshing feeling is 1 point or more.
〇: The difference in the average score of refreshing feeling is more than 0 points and less than 1 point.
×: The difference in the average score of the refreshing feeling is 0 points or less.

In Tables 1 and 2 and Table 3 below, the "appropriate amount" is the amount of the pH adjuster required to adjust the pH of the ophthalmic composition to 7. The "remaining amount" is the amount of purified compound (w / v%) required to make the total amount of the ophthalmic composition 100 mL.

As is clear from Tables 1 and 2, the ophthalmic compositions obtained in each example were able to sufficiently improve eye strain.
By using the ophthalmic compositions obtained in Examples 5 to 8 while wearing soft contact lenses, an excellent refreshing sensation was obtained, and the refreshing sensation was also excellent in sustainability.

[Prescription Examples 1 to 16]
Aqueous components other than purified water and a pH adjuster were dissolved in 90 mL of purified water to prepare an aqueous solution B2 so that the composition shown in Tables 3 to 5 was obtained, and the obtained aqueous solution B2 was kept at room temperature (25 ° C.) for 15 minutes. Stirred and mixed. When an oily component other than the terpenoid was blended, a predetermined amount of a mixture of the oily component and a solubilizer (nonionic surfactant) prepared separately was added to the aqueous solution B2, and the mixture was stirred and mixed at 90 ° C. for 15 minutes. When blending terpenoids, a predetermined amount of a mixture of terpenoids and a solubilizer (at least one of a nonionic surfactant and propylene glycol) prepared separately was added to the aqueous solution B2, and the mixture was stirred and mixed at room temperature (25 ° C.) for 15 minutes. ..
Then, after adjusting the pH of the ophthalmic composition with a pH adjuster as necessary so that the pH at 25 ° C. becomes 7, the remaining purified water is added so that the total volume becomes 100 mL, and the ophthalmic composition is used for ophthalmology. The composition was obtained. As the pH adjuster, at least one of hydrochloric acid and sodium hydroxide was used. A pH meter (manufactured by DKK-TOA CORPORATION, trade name "HM-25R") was used for pH measurement.
When the osmotic pressure of the obtained ophthalmic composition was measured in the same manner as in Example 1, it was confirmed that the osmotic pressure was within the range of 220 to 260 mOsm. Moreover, when the effect of improving eye strain was evaluated in the same manner as in Example 1, it was confirmed that the eye strain could be sufficiently improved.
The "unit" in Tables 3 to 5 means that the unit of the blending amount of the retinol palmitate ester, which is vitamin A, is "unit / 100 mL". For example, "50,000 units" means that the blending amount of retinol palmitate is "50,000 units / 100 mL".

Claims (4)

An ophthalmic composition for improving eye strain having an osmotic pressure of 220 to 260 mOsm. The ophthalmic composition for improving eye strain according to claim 1, which comprises a terpenoid. At least one selected from the group consisting of buffers, edetic acids, edetates, decongestants, astringents, anti-inflammatory agents, antihistamines, vitamins, amino acids, water-soluble high molecular weight compounds, and nonionic surfactants. The ophthalmic composition for improving eye fatigue according to claim 1 or 2, further comprising a seed component. The ophthalmic composition for improving eye strain according to any one of claims 1 to 3, which is for contact lenses.