TW201841658A - Ophthalmic composition - Google Patents

Abstract

Provided is an ophthalmic composition from which sesame oil or castor oil can be released easily by the dilution with a tear fluid and therefore the sesame oil or castor oil can be supplied to a tear oil layer. An ophthalmic composition containing (A) at least one oil selected from (A-1) sesame oil and (A-2) castor oil and (B) a nonionic surfactant selected from (B-1) polyoxyethylene castor oil, (B-2) polyoxyethylene hydrogenated castor oil and (B-3) another nonionic surfactant, wherein the blend ratios of these components by mass meet the requirement, and the permeability of the composition is 70% or more.

Description

Ophthalmic composition

The present invention relates to an ophthalmic composition containing one or more selected from (A-1) sesame oil and (A-2) castor oil.

The tear oil layer contains lipids secreted from the meibomian gland. It is known that the lipids are constantly saturated due to age or hormonal changes. It is further known that this is exacerbated by wearing contact lenses. The tear oil layer becomes unstable due to constant saturation, which is a cause of dry eye or eye fatigue. It has been reported that for the stabilization of the tear oil layer, an aqueous composition containing a vegetable oil is effective (Patent Document 1: International Publication No. 2013/008714), and various aqueous ophthalmic compositions containing a vegetable oil have been proposed. However, these compositions cannot sufficiently supply oil to the tear oil layer. In addition, if the blending amount of vegetable oil is increased in order to increase the supply amount of oil, it becomes a suspension preparation, and there is a problem that it is difficult to determine the presence or absence of foreign matter. In addition, the suspended preparation becomes whitish, hazy, etc. before the eyes are dropped, which poses a problem in terms of use feeling. [Prior Art Literature] [Patent Literature]

[Patent Document 1] International Publication No. 2013/008714

[Problems to be Solved by the Invention] The present invention has been made in view of the above circumstances, and an object thereof is to provide an ophthalmic composition selected from (A-1) sesame oil and (A-2) One or more of castor oils are easily released from the composition by dilution with tear fluid, and these can be supplied to the tear fluid layer, and the appearance of the ophthalmic composition is clear.

[Means for Solving the Problem] The inventors of the present invention conducted diligent research in order to achieve the above-mentioned object, and as a result, found that one or more members selected from (A-1) sesame oil and (A-2) castor oil were used. In addition, a composition having a limited type and ratio of nonionic surfactants is used as a composition to ensure clarity, and after application to the eye, it is diluted by tears to separate (A) the component and float, which can give The oil-releasing property (hereinafter sometimes referred to as the dilution-releasing property of (A) component) diluted with tear fluid has completed the present invention.

Therefore, the present invention provides an ophthalmic composition and a method for producing the same. [1]. An ophthalmic composition comprising: (A) one or more selected from (A-1) sesame oil and (A-2) castor oil; and (B) a nonionic surfactant, (B) The component contains one or more nonionic surfactants selected from (B-1) polyoxyethylene castor oil, (B-2) polyoxyethylene hydrogenated castor oil, and (B-3) other nonionic surfactants, the Some blending quality ratios satisfy 0.05 ≦ [(B-1) + (B-2) + (B-3)] / (A) [(B-1) /0.5+ (B-2) /0.5+ (B -3) /0.05] / [(A-1) + (A-2)] × (A-1) / [(A-1) + (A-2)] + [(B-1) /0.2+ (B-2) /0.25+ (B-3) /0.05] / [(A-1) + (A-2)] × (A-2) / [(A-1) + (A-2)] ≦ 10.0 and the transmittance of the ophthalmic composition is 70% or more. [2]. The ophthalmic composition according to [1], wherein (B) the nonionic surfactant comprises a member selected from (B-1) polyoxyethylene castor oil and (B-2) polyoxyethylene hydrogenated castor oil More than one of them. [3]. The ophthalmic composition according to [1] or [2], which is used to reduce friction at the moment of blinking. [4] A method for producing an ophthalmic composition, the ophthalmic composition according to any one of [1] to [3], the method comprising finely emulsified by high pressure化 步骤。 The step.

[Effects of the Invention] According to the present invention, it is possible to provide an ophthalmic composition which, as a composition, ensures clarity, and after application to the eye, is diluted with tear fluid and separated from oil components and floats, and can be imparted with tear fluid. Diluted oil-releasing properties, the ophthalmic composition is preferably used to reduce friction at the moment of sight.

Hereinafter, the present invention will be described in detail. [(A) Component] One or more selected from (A-1) sesame oil and (A-2) castor oil. Sesame oil and castor oil are vegetable oils containing fatty acid triglyceride as a main component. Sesame oil contains a large amount of oleic acid and linoleic acid as unsaturated fatty acids, and castor oil contains a large amount of ricinoleic acid as unsaturated fatty acids. The sesame oil and castor oil that can be blended in the ophthalmic composition of the present invention are not particularly limited as long as they are medically, pharmacologically (pharmaceutically), or physiologically acceptable. For example, a commercially available product can be used from a seed obtainer using a known extraction method or a known purification method. From the viewpoint of clarification or releasability by dilution with tears, sesame oil and castor oil that meet the standards of the 17th edition of the revised Japanese Pharmacopoeia are preferred.

(A): The total amount of (A-1) and (A-2) components in the composition is preferably 0.001 W / V% to 2 W / V% (mass / volume%, g / 100 mL, The same applies hereinafter), more preferably 0.001 W / V% to 1.8 W / V%, and still more preferably 0.001 W / V% to 0.8 W / V%. Within the above range, the clarification and the diluted release property of the component (A) become more favorable.

[(B) Component] As (B) nonionic surfactant, it can be classified into (B-1) polyoxyethylene castor oil (sometimes described as POE castor oil), (B-2) polyoxyethylene hydrogenated castor oil (May be described as POE hydrogenated castor oil), (B-3) Other non-ionic surfactants. The component (B) can maintain the dilution release property of the component (A) even if it is blended at a higher concentration. Therefore, it is preferable to use a component selected from (B- 1) One or more of polyoxyethylene castor oil and (B-2) polyoxyethylene hydrogenated castor oil. Furthermore, in terms of storage stability or clarity of the composition, it is more preferable to mix two or more nonionic surfactants.

(B-1) Polyoxyethylene castor oil Polyoxyethylene castor oil is a well-known compound obtained by adding polymerized ethylene oxide to castor oil, and there are known several types in which the average addition mole number of ethylene oxide is different. The average addition mole number of ethylene oxide in polyoxyethylene castor oil is not particularly limited, and examples include 3 to 60 moles. Specifically, polyoxyethylene castor oil 3, polyoxyethylene castor oil 10, polyoxyethylene castor oil 20, polyoxyethylene castor oil 35, polyoxyethylene castor oil 40, polyoxyethylene castor oil 50, poly Oxyethylene castor oil 60, etc. (the value is the average addition mole number of ethylene oxide). These polyoxyethylene castor oils can be used singly or in a suitable combination of two or more. Among these, polyoxyethylene castor oil 35 is preferably used in terms of lower irritation.

The blending amount when blending the (B-1) component is not particularly limited as long as it satisfies the following ratio. In the composition, it is preferably 0.000005 W / V% to 10 W / V%, and more preferably 0.00005 W / V%. -9 W / V%, more preferably 0.0001 W / V% to 4 W / V%. Within the above range, the clarification and the diluted release property of the component (A) become more favorable.

(B-2) Polyoxyethylene hydrogenated castor oil Polyoxyethylene hydrogenated castor oil (POE hydrogenated castor oil) is a compound obtained by adding polymerized ethylene oxide to hydrogenated castor oil, and the average addition of ethylene oxide is known There are several species with different Morse numbers. The average addition mole number of ethylene oxide in the polyoxyethylene hydrogenated castor oil is not particularly limited, and examples include 5 to 100 moles. Specifically, polyoxyethylene hydrogenated castor oil 5, polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 30, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene Hydrogenated castor oil 50, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 80, polyoxyethylene hydrogenated castor oil 100, etc. (the value is the average addition mole number of ethylene oxide). These polyoxyethylene hydrogenated castor oils may be used singly or in a suitable combination of two or more. Among these, polyoxyethylene hydrogenated castor oil 40 and polyoxyethylene hydrogenated castor oil 60 are preferably used in terms of lower irritation.

The blending amount when blending the (B-2) component is not particularly limited as long as it satisfies the following ratio. In the composition, it is preferably 0.000005 W / V% to 10 W / V%, more preferably 0.00005 W / V% -9 W / V%, more preferably 0.0001 W / V% to 4 W / V%. Within the above range, the clarification and the diluted release property of the component (A) become more favorable.

(B-3) Other nonionic surfactants Examples of nonionic surfactants other than (B-1) and (B-2) include polysorbate 80 (polyoxyethylene (20) sorbitan oleic acid). Esters) represented by polyoxyethylene sorbitan fatty acid esters (POE sorbitan fatty acid esters) and polyoxyethylene-polyoxypropylene block copolymers (POEPOP diols) represented by poloxamer Polyethylene glycol monostearate (PEG monostearate) represented by polyethylene glycol monostearate (10), etc., can be used alone or in a suitable combination of two or more. Among these, in terms of the dilution release property of the (A) component, it is preferably selected from phospholipids such as lecithin or hydrogenated lecithin, phosphatidylcholine, and phosphatidyl glycerol, which are difficult to desorb from the interface. It is preferable that the nonionic surfactant other than the above is substantially free of the above-mentioned lecithin and the like.

The blending amount when blending the (B-3) component is not particularly limited as long as it satisfies the following ratio. In the composition, it is preferably 0.000005 W / V% to 1 W / V%, more preferably 0.00005 W / V% ∼0.9 W / V%, more preferably 0.0001 W / V% to 0.4 W / V%. Within the above range, the clarification and the diluted release property of the component (A) become more favorable.

(B) Non-ionic surfactant The non-ionic surfactant is formulated at the following formulation mass ratio. 0.05 ≦ [(B-1) + (B-2) + (B-3)] / (A) [(B-1) /0.5+ (B-2) /0.5+ (B-3) /0.05] / [(A-1) + (A-2)] × (A-1) / [(A-1) + (A-2)] + [(B-1) /0.2+ (B-2) / 0.25+ (B-3) /0.05] / [(A-1) + (A-2)] × (A-2) / [(A-1) + (A-2)] ≦ 10.0 (B-1 ) Polyoxyethylene castor oil (B-2) Polyoxyethylene hydrogenated castor oil (B-3) Other non-ionic surfactants

In addition, in the present invention, a unit of "W / V% (mass / volume%, g / 100 mL)" is used as the blending amount of each component. However, in the above formula, the mass ratio and W / V% are expressed. The ratio becomes the same value.

[(B-1) + (B-2) + (B-3)] / (A) is the lower limit for the deployment of (B) component, if it does not satisfy 0.05 ≦ [(B-1) + (B-2) + (B-3)] / (A), the target transmittance cannot be obtained. The ratio is more preferably 0.5 ≦, and further preferably 1.0 ≦. The upper limit value is not particularly limited, but is usually 10 or less.

The upper allocation limit is [(B-1) /0.5+ (B-2) /0.5+ (B-3) /0.05] / [(A-1) + (A-2)] × (A-1) / [ (A-1) + (A-2)] + [(B-1) /0.2+ (B-2) /0.25+ (B-3) /0.05] / [(A-1) + (A-2 )] × (A-2) / [(A-1) + (A-2)] ≦ 10.0, preferably ≦ 8.0, and more preferably ≦ 7.5. If it exceeds 10.0, the target (A) component's diluted release property cannot be obtained. The lower limit value is not particularly limited, but is usually 0.01 or more.

The formula for determining the upper limit of formulation is (B) non-ionic surfactant / (A) component. The upper limit of blending varies according to the type of the (B) nonionic surfactant. Therefore, the amount of the component (B) is divided by the coefficient specific to the type of the component (B) for each type of the component (B). . The inherent coefficient means that, for example, regarding (B-1) /0.2 and (B-3) /0.05, it means that the upper limit of deployment of (B-1) is 4 times (0.2 / 0.05) higher than (B-3). In addition, depending on the type of the (A) component, the upper limit of each active ingredient of the (B) component is different, so [(B-1) /0.5+ (B-2) /0.5+ (B-3) /0.05] represents each (B) The upper limit of blending of components with respect to (A-1), [(B-1) /0.2+ (B-2) /0.25+ (B-3) /0.05] means that each (B) component is relative to (A -2) upper limit of deployment. Divide these by the sum of (A) components (A-1) + (A-2). Furthermore, in the case where both (A-1) and (A-2) are included, the influence is larger or smaller according to the deployment ratio. Therefore, as its weight, it is multiplied by (A-1) / [(A- 1) + (A-2)] and (A-2) / [(A-1) + (A-2)].

(C) Terpenes The composition of the present invention may further contain (C) terpenes. The blending of terpenes can further improve the dilution release of the component (A). (C) A component can be used individually by 1 type or in combination of 2 or more types suitably. The terpenes of the present invention have a structure having an isoprene unit as a constituent unit, and examples thereof include terpene, terpene alcohol, terpene aldehyde, and terpene ketone. In addition, there are monoterpenes, sesquiterpenes, diterpenes, triterpenes, and tetraterpenes depending on the carbon number. Specific examples include monoterpenes such as menthol, menthol, camphor, borneol, borneol, geraniol, eucalyptol, linalool, citronellol, and limonene, and retinol and retinaldehyde. Terpenes, such as terpenes, carotenoids, etc. Among these, monoterpene is preferably used. These terpenes may be used in any of d-form, l-form, or d-form. Among them, menthol, menthol, camphor, borneol, geraniol, eucalyptol, and linalool, more preferably menthol, camphor, borneol, geraniol, eucalyptol, and linalool. Especially preferred is menthol. Furthermore, in the present invention, as the terpenoid, an essential oil containing the compound may be used. Examples of such essential oils include eucalyptus oil, citrus oil, fennel oil, rose oil, Japanesemint ( Mentha arvensis L. ) oil, Peppermint ( Mentha piperita L. ) oil, and green Peppermint oil, and essential oils of borneol, rosemary oil, lavender oil, etc. In terms of improving the dilution release property of the component (A), citrus oil and eucalyptus oil are preferred.

In the case of compounding (C) component, although the compounding amount also depends on the type of (C) component, and the type and content of other compounding components (especially the surfactant), it is preferably 0.0001 W / V% in the composition. ~ 0.2 W / V%, more preferably 0.001 W / V% to 0.1 W / V%. In these blending concentration ranges, regardless of the kind or blending amount of other blending ingredients, (C) there is less concern about the precipitation of terpenes. In addition, in terms of improving the dilution release property and clarity of the component (A), it is more preferably 0.005 W / V% or more, and from the viewpoint of reducing irritation, it is more preferably 0.075 W / V% or less.

[Other components] To the extent that the effects of the present invention are not impaired, an appropriate amount of other components may be blended in the composition of the present invention. Examples of the other components include oil components other than sesame oil and castor oil, preservatives, sugars, buffering agents, pH adjusting agents, tonicity agents, stabilizers, polyols, thickeners, and drugs. These components may be formulated alone or in a suitable combination of two or more.

Examples of oil components other than sesame oil and castor oil include soybean oil, olive oil, corn oil, coconut oil, almond oil, medium-chain fatty acid triglycerides, white petrolatum, purified lanolin, cholesterol, and acetic acid-d- Vitamin A such as α-tocopherol, mixed tocopherol, liquid paraffin, and retinyl palmitate. The blending amount of the oil component in the composition is preferably 0.001 W / V% to 1.0 W / V%, more preferably 0.001 W / V% to 0.5 W / V%, and most preferably 0.001 W / V% to 0.25 W / V%.

Examples of the preservative having a hydrophobic part such as an alkyl chain or a benzene ring include thimerosal, phenylethyl alcohol, alkylaminoethylglycine, and gluconic acid chloride. Chlorhexidine gluconate, methyl paraoxybenzoate, ethyl paraoxybenzoate, etc., but it is difficult to migrate the component (A) in the composition of the present invention to the tear oil layer, so it is preferred in the composition It is 1.0 W / V% or less, and more preferably it is substantially not included.

Examples of the saccharides include glucose, cyclodextrin, xylitol, sorbitol, and mannitol. Furthermore, these may be any of d-body, l-body, or dl-body. The blending amount of saccharides in the composition is preferably 0.001 W / V% to 5.0 W / V%, more preferably 0.001 W / V% to 1 W / V%, and still more preferably 0.001 W / V% to 0.1 W / V%.

Examples of the buffering agent include citric acid, sodium citrate, boric acid, borax, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, glacial acetic acid, tromethamine, and sodium bicarbonate. The blending amount of the buffering agent in the composition is preferably 0.001 W / V% to 5.0 W / V%, more preferably 0.001 W / V% to 2 W / V%, and even more preferably 0.001 W / V% to 1 W. / V%.

Examples of the pH adjusting agent include inorganic acids and inorganic alkali agents. Examples of the inorganic acid include (dilute) hydrochloric acid. Examples of the inorganic alkaline agent include sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium bicarbonate. The pH of the composition is preferably 3.5 to 8.0, and more preferably 5.5 to 8.0. The pH was measured at 25 ° C using a pH meter (HM-25R, East Asia DKK (stock)).

Examples of the tonicity agent include sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, dried sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate. It is better to make tension. The relative physiological saline osmotic pressure of the composition 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 was measured at 25 ° C using an automatic osmometer (A2O, Advanced Instruments).

Examples of the stabilizer include sodium edetate, cyclodextrin, sulfite, dibutylhydroxytoluene, and the like. The blending amount of the stabilizer in the composition is preferably 0.001 W / V% to 5.0 W / V%, more preferably 0.001 W / V% to 1 W / V%, and further preferably 0.001 W / V% to 0.1 W. / V%.

Examples of the polyhydric alcohol include glycerin, propylene glycol, butylene glycol, and polyethylene glycol. In the case of blending a polyol, the blending amount of the polyol in the composition is preferably 0.001 W / V% to 5.0 W / V%, more preferably 0.001 W / V% to 1 W / V%, and even more preferably 0.001 W / V% to 0.1 W / V%.

Examples of the viscosity agent include polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, and polyacrylic acid. , Carboxy vinyl polymers, etc. In the case of blending a thickener, the blending amount in the composition is preferably 0.001 W / V% to 5.0 W / V%, more preferably 0.001 W / V% to 1 W / V%, and further preferably 0.001 W. / V% to 0.1 W / V%.

Examples of the drug (pharmaceutical active ingredient) include decongestant components (eg, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, and naphazoline salts). Acid salt, naphthozoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, etc.), anti-inflammatory astringent agents (eg, neostigmine methyl sulfate, ε-aminocaproic acid, allantoin, berberine chloride hydrate, berberine sulfate hydrate, sodium sulfonate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate, lysozyme hydrochloric acid Salt, etc.), antihistamines (for example, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), water-soluble vitamins (flavin adenine dinucleotide Sodium (flavin adenine dinucleotide sodium), cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, etc., amino acids (eg, L-day Potassium aspartate L- aspartic acid amide, magnesium, potassium L- asparagine Magnesium (equimolar mixture), aminoethyl sulfonic acid, chondroitin sulfate, etc.), sulfonamides (sulfa drug) and the like. In the case of formulating drugs, the effective content of each drug can be selected for the content of the drug, but it is preferably 0.001 W / V% to 5.0 W / V%, and more preferably 0.001 W / V% to the composition. 1 W / V%, more preferably 0.001 W / V% to 0.1 W / V%.

[Manufacturing method] The manufacturing method of the composition of the present invention is not particularly limited, and can be obtained, for example, by mixing a mixed solution of an oily component such as (A) component and a surfactant component such as (B) component with an aqueous solution After the components of the aqueous solution were mixed and adjusted for pH, the total volume was adjusted with water. The mixing method of each liquid can be a general method, and it is suitable to use a pulsator, a propeller blade, a blade, a turbine blade, etc. There is no restriction | limiting in rotation speed, It is preferable to set it to the level which does not blister intensely. . The mixing temperature of each liquid is not particularly limited, and it is preferred that both the oily component and the surfactant component are above the melting temperature. It is more preferable to perform a miniaturization step by high-pressure emulsification. Regarding high-pressure emulsification conditions, from the viewpoint of improving the clarity of the composition, it is preferable to increase the number of passes under high pressure, and from the viewpoint of improving production efficiency, it is preferable to reduce the number of passes under low pressure, and the injection pressure is better. It is 100 MPa to 245 MPa, and more preferably 200 MPa to 245 MPa. It is preferable to further apply back pressure, and it is preferably 3 MPa to 10 MPa, and more preferably 3 MPa to 5 MPa. Furthermore, the number of passes is preferably 1 to 10 times, and more preferably 1 to 5 times.

In addition, after the obtained composition is filled in a resin container, it may be sealed with a packaging body, and an inert gas may be sealed in a space formed between the container and the packaging body. The resin container was filled with the composition, and sealed with a package together with a deoxidizer.

[Composition for Ophthalmology] The composition of the present invention is preferably an "aqueous composition for ophthalmology". In the present invention, the "aqueous ophthalmic composition" refers to an ophthalmic composition whose vehicle is water. In addition, in terms of being easily mixed with tears and allowing the component (A) to migrate to tears, the amount of water blended in the composition is preferably 90.0 W / V% to 99.5 W / V%, and more preferably 95.0 W / V% ～ 99.5 W / V%.

The composition of the present invention is preferably a liquid from the viewpoint of easily adapting to the eyes, and the viscosity at 25 ° C. is preferably 20 from the point that it is easy to mix with tears so that the component (A) easily migrates to tears. mPa · s or less, more preferably 10 mPa · s or less, and even more preferably 5 mPa · s or less. The viscosity is measured using a cone-plate viscometer (DV2T, Hidehiro Seiki Co., Ltd.).

The transmittance of the composition of the present invention is 70% or more, preferably 90% to 100%, and more preferably 95% to 100% or more in terms of easy discovery when foreign matter is mixed. The transmittance is a transmittance at a wavelength of 600 nm measured using a spectrophotometer (for example, UV-1800, Shimadzu Corporation).

The particle diameter (median particle diameter) of the association of the surfactant and the component (A) contained in the composition of the present invention is related to the transmittance, and is preferably 300 nm or less, more preferably 200 nm or less, and furthermore, It is preferably below 50 nm. The particle diameter is measured using a particle diameter measuring device (for example, ELSZ-200ZS, manufactured by Otsuka Electronics Co., Ltd.).

The composition of the present invention can be preferably used as an eye drop, an eye drop for contact lenses, an eye wash, and the like. Since the component (A) has good dilution release property, it can be preferably used as an eye drop and contact lenses. Eye drops (eye drops for contact lens wearers). Contact lenses are not particularly limited to rigid contact lenses, O ₂ rigid contact lenses, soft contact lenses, silicone hydrogel soft contact lenses, and the like.

When used as an eye drop or an eye drop for contact lenses, it is preferably 30 μL to 60 μL each time and 5 to 6 times per day, more preferably 30 μL to 50 μL each time and one day Drop 5 times to 6 times. In the case of using as an eye wash, it is preferably 3 mL to 6 mL each time and eye wash 3 to 6 times per day.

The component (A) in the composition of the present invention has good dilution release property, can replenish a large amount of oil to the tear oil layer, and can reduce friction at the instant. It is preferably used for reducing the friction at the moment of the eye, and effectively improves the symptoms (foreign body sensation and dryness) caused by the friction between the eyelid marginal conjunctiva and the corneal surface. In addition, the dry eye symptoms are caused by the friction at the instant of eye, so it can effectively improve the dry eye symptoms (eye fatigue, blurred eyes, dry eyes, dryness, foreign body sensation, eye pain, dazzling, eyelid weight, itchy eyes, eye discomfort Sensation, eye fat, tears, congestion, etc.). It is effective for patients with dry eye due to the above aspects. Furthermore, since the friction with the eyelids increases due to wearing contact lenses, it is preferably used for contact lens wearers, especially for soft contact lens wearers.

The effective amount, the method of administration, and the formulation are as described above. For example, as an amount of the component (A), each adult is administered once to six times a day for 0.0001 mg to 1 mg. [Example]

The present invention will be specifically described below with examples and comparative examples, but the present invention is not limited to the following examples. In addition, in the following examples, unless otherwise specified, the composition "%" represents W / V%, and the ratio represents "mass ratio".

[Examples and Comparative Examples] Each of the aqueous components in the following table was dissolved in 90 mL of water, and heated and mixed at 90 ° C for 15 minutes. At the same time, a premix of (A) component and (B) non-ionic surfactant 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 further heated and mixed at 90 ° C for 15 minutes. Then, it cooled to room temperature, adjusted pH, and added water so that the total amount might become 100 mL. Furthermore, a high-pressure emulsifier (Star Burst Mini, sugino machine (stock)) was used to perform five treatments at a spray pressure of 200 MPa and a back pressure of 3 MPa to prepare eye drops (in the table, the rest Part of it). The following eye drops were evaluated. The results are described in a table together.

[Transmittance] The transmittance at a wavelength of 600 nm was measured using a UV-visible near-infrared spectrophotometer UV-1800 (Shimadzu Corporation) for the composition shortly after production. Pass 70% or more.

[Releasability by diluted (A) component] It is said that the average human tear is 7 μL, and when 30 to 60 μL of eye drops are instilled, the tear will be diluted about 1.12 times to 1.23 times . In this test, in order to evaluate the composition (sample) that was diluted by tears and the component (A) floated at the air-liquid interface (releasability), a normal saline was used as the model tear and the composition was diluted at a dilution factor of 1.2. The oil component on the water surface is free. Use a measuring bottle with a narrow opening (the inner diameter of the opening is about 150 mm ² ) for easy observation (specifically, 10 mL of physiological saline is added to a 50 mL measuring bottle, and the composition is injected into the opening) . Regarding the observation of the (A) component on the water surface, the liquid surface was irradiated with light using a fluorescent lamp as a light source, and the interference light of the oil floating to the liquid surface was observed, and evaluated according to the following criteria. Set the ● above to pass. [Evaluation Criteria] ◎: Interference light from the oil was observed, and occupied the entire surface of the opening portion of the measuring flask. ○: Interference light from the oil was observed, and although it did not cover the entire surface of the opening of the measuring flask, it was 50% or more. ●: Interference light from oil was observed, and the proportion in the opening of the measuring flask was less than 50%. X: No interference light from the oil was observed.

Example 13, Comparative Example 2, Comparative Example 5 to Comparative Example 7 were evaluated as described below. [Coefficient of Dynamic Friction] It is said that the tear fluid of an average person is 7 μL, and thus when the eye drops of 30 μL to 60 μL are instilled, the tear fluid will be diluted about 1.12 times to 1.23 times. In this test, 1.5 mL of normal saline as a model tear was added to a polystyrene petri dish, and 8.5 mL of each eye drop was added so that the dilution ratio became about 1.2 times. Furthermore, a double-sided tape was used to adhere the artificial skin (Bio Skin) (Trinity Lab (stock)) to the Handy tribometer (TL-701, Trinity Lab) (Strand)), press the terminal against the bottom surface of the previous polystyrene culture dish, and adjust so that the load becomes 0.6 N. In this state, the coefficient of kinetic friction during the rotation of the polystyrene Petri dish at 80 mm / s was measured. The lower the dynamic friction coefficient, the easier the surface of the petri dish is to slide. The reduction of friction at the surface of the petri dish implies that the present invention has the effect of smoothing blinking by reducing the friction generated between the eyelid conjunctiva and the corneal surface.

[Evaluation of Reduction of Friction at the Sight] The test subject is a person whose degree of friction at the dazzle is 7 or more according to the following evaluation criteria. Eye drops were instilled into two eyes at 30 μL per eye, and the degree of friction at the instant of eye drops was evaluated using a numerical evaluation scale. That is, regarding the "friction at the moment of blinking", how much the character feels at the moment of blinking by selecting one of 11 values from 0 (no friction at all) to 10 (very much feeling of friction). The friction is scored. The results are expressed as an average of 3 persons.

[Table 1]

[Table 2]

[table 3]

[Table 4]

[table 5]

[TABLE 6]

[TABLE 7]

[TABLE 8]

[TABLE 9]

[TABLE 10]

In the composition of 0.05 ＞ [(B-1) + (B-2) + (B-3)] / (A) (Comparative Example 1, Comparative Example 3), the transmittance is less than 70%. When the composition is 0.05 ≦ [(B-1) + (B-2) + (B-3)] / (A), the transmittance becomes 70% or more. In addition, we can know: [(B-1) /0.5+ (B-2) /0.5+ (B-3) /0.05] / [(A-1) + (A-2)] × (A-1) / [ (A-1) + (A-2)] + [(B-1) /0.2+ (B-2) /0.25+ (B-3) /0.05] / [(A-1) + (A-2 )] (A-2) / [(A-1) + (A-2)]> 10.0 (Comparative Example 2, Comparative Example 4), the dilution of the component (A) (oil component) could not be obtained Release, but by making [(B-1) /0.5+ (B-2) /0.5+ (B-3) /0.05] / [(A-1) + (A-2)] × (A -1) / [(A-1) + (A-2)] + [(B-1) /0.2+ (B-2) /0.25+ (B-3) /0.05] / [(A-1) A composition with + (A-2)] × (A-2) / [(A-1) + (A-2)] ≦ 10.0 can obtain the dilution release property of the (A) component (oil component).

The raw materials used in the examples are shown below. In addition, as long as there is no special indication, the amount of each component in the table is a purity conversion amount. Sesame oil: castor oil manufactured by Kaneda (stock): special grade A, POE castor oil 35 manufactured by Ito Oil (stock), Unioxs C35, and POE hydrogenated castor oil 40: HCO40, manufactured by Nippon Oil (stock) Polyurethane hydrogenated castor oil 60: HCO60 manufactured by Japan Surfactant Industry Co., Ltd. Polyethylene glycol monostearate manufactured by Japan Surfactant Industry Co., Ltd. * 1: Average addition of ethylene oxide Molar number is 10 (MYS10V, manufactured by Japan Surfactant Industry Co., Ltd.) Polyethylene glycol monostearate * 2: The average addition mole number of ethylene oxide is 40 (MYS40MV, Japanese interface activity Surfactant (manufactured by Surfactant) Polyethylene glycol monostearate * 3: The average addition mole number of ethylene oxide is 100 (EMALEX 8100, manufactured by Nihon emulsion (Stock)) POE sorbitan Fatty acid ester: Polysorbate 80, POEPOP diol manufactured by Kao (stock): Lutrol F127, boric acid manufactured by BASF (stock): Glycerol manufactured by Kanto Chemical (stock): Kanto Chemical (stock) Production of sodium edetate hydrate: Clewat N, Nagase Kasei Co., Ltd. Production of sodium chloride: Tomita Pharmaceutical Co., Ltd. Production of sodium hydroxide: Wako Pure Chemical Industries, Ltd. Production of menthol: l- Menthol, Suzuki Mint (stock) made dl-camphor: Nippon Seika (stock) made Borneol: d-borneol, Yanagisawa Masaki store (stock) made geraniol: Takasago perfume industry (stock) made eucalyptus oil: Takasago perfume Industrial (stock) manufacturing agarwood alcohol: Takasago fragrance industry (stock) manufacturing citrus oil: Yamamoto fragrance (stock) manufacturing Eucalyptus oil: Ogawa fragrance (stock) manufacturing

no

no

Claims (4)

An ophthalmic composition comprising: (A) one or more selected from (A-1) sesame oil and (A-2) castor oil; and (B) a nonionic surfactant, and (B) a component comprising (B-1) polyoxyethylene castor oil, (B-2) polyoxyethylene hydrogenated castor oil, and (B-3) other nonionic surfactants, and the quality of the preparation The ratio satisfies 0.05 ≦ [(B-1) + (B-2) + (B-3)] / (A) [(B-1) /0.5+ (B-2) /0.5+ (B-3) / 0.05] / [(A-1) + (A-2)] × (A-1) / [(A-1) + (A-2)] + [(B-1) /0.2+ (B-2 ) /0.25+ (B-3) /0.05] / [(A-1) + (A-2)] × (A-2) / [(A-1) + (A-2)] ≦ 10.0, and The transmittance of the ophthalmic composition is 70% or more. The ophthalmic composition according to item 1 of the scope of patent application, wherein (B) the nonionic surfactant is selected from (B-1) polyoxyethylene castor oil and (B-2) polyoxyethylene hydrogenated castor oil More than one. The ophthalmic composition according to item 1 or 2 of the scope of patent application, which is used to reduce friction at the moment of blinking. A method for manufacturing an ophthalmic composition, the ophthalmic composition according to any one of claims 1 to 3 of the patent application scope, the method comprising miniaturization by high-pressure emulsification step.