JP6304475B2 - Eye drops - Google Patents

Description

  The present invention relates to eye drops.

In recent years, due to an increase in personal computer work and the like, the number of patients complaining of blurred eyes caused by tired eyes and eyes has increased, which has become a serious problem.
As means for improving such blurred eye symptoms, ingestion of foods such as blueberries, surgical operations, eye drops and the like are known. Patent Document 1 discloses an eye mask and an ointment containing proanthocyanidins. The use of is proposed.
However, there is a demand for a method for improving blurring that is safer and more effective.

  On the other hand, it is known that the usage amount of one drop of eye drops is usually 29.5 to 53 μL (Non-patent Document 1), and avoids the occurrence of periocular dermatitis or the like due to the chemical overflowing from the eye. For this purpose, a technique for reducing the amount of one drop of eye drops is known (Patent Document 2), but the relationship between such a technique and blurred eyes is not known at all. Currently.

JP 2004-277350 A Japanese Patent Laying-Open No. 2005-211884

Hiroaki Ikeda and five others, “Information on Medical Eye Drops Necessary for Proper Use”, Hospital Pharmacy, 1998, 24 (6), p. 595-600

  This invention is made | formed in view of the said situation, Comprising: It aims at providing the eye drop with the high improvement effect with respect to the haze of an eye.

In order to solve the above-mentioned problems, the present inventors have conducted intensive research. As a result, the eye drops are formulated with an eye drop that contains a predetermined component and can be instilled with a predetermined amount of one drop. We found that it can be remarkably improved.
In addition, the present inventors said that when the amount of eye drops containing either a nonionic surfactant or a thickener is designed to be small, the amount of drops per droplet varies. A new problem has been found, and the problem has been solved by including both a nonionic surfactant and a thickening agent, and it has been found that variations in the amount of the eye drop per drop are suppressed.
Further, the present inventors have found a new problem that the eye drop effectiveness is low in the eye drop with a small amount per drop, and the problem is that the eye drop contains a nonionic surfactant and a non-ionic surfactant. It has been found that by adding a thickener, the effect of eye drops is enhanced.
That is, the present invention provides the following (1) to (11).
(1) The eye drop of the present invention is an eye drop containing (A) a nonionic surfactant and (B) a thickener, and the drop amount per drop is 5 to 25 μL. And
(2) The eye drop of the present invention is preferably filled in a container having an internal volume of 4 to 30 mL.
(3) It is preferable that the eye drop of the present invention is further filled in a container having a nozzle having an inner diameter of less than 1.5 mm at the dropping port.
(4) In the eye drop of the present invention, the nonionic surfactant contains polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, poloxamers, and polyethylene monostearate It is preferably at least one selected from the group consisting of glycols.
(5) In the eye drop of the present invention, the thickener is at least one selected from the group consisting of carboxyvinyl polymer, hydroxypropylmethylcellulose, hydroxyethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, alginic acid, and sodium hyaluronate. Preferably there is.
(6) It is preferable that the eye drop of the present invention further contains (C) a terpenoid compound.
(7) In the eye drop of the present invention, the terpenoid compound is at least one selected from the group consisting of dl-menthol, l-menthol, dl-camphor, d-camphor, d-borneol, and geraniol. Is preferred.

(8) A method for imparting a blurred vision improving action to the eye drop of the present invention comprises (A) a nonionic surfactant and (B) a thickener in an eye drop, and one drop of the eye drop It is designed so that the amount of per drop is 5 to 25 μL.
(9) A method for suppressing variations in the amount of one drop of the eye drop of the present invention comprises (A) a nonionic surfactant and (B) a thickener in the eye drop, and 1 of the eye drop It is designed so that the dropping amount per drop is 5 to 25 μL.
(10) In the method for improving the effectiveness of eye drops according to the present invention, the eye drop contains (A) a nonionic surfactant and (B) a thickener, and the amount of the eye drop per drop is 5 It is designed to be ˜25 μL.
(11) In the method for producing an eye drop in a container according to the present invention, the amount of the eye drop containing (A) a nonionic surfactant and (B) a thickener is 5 to 25 μL per drop. It is characterized by filling the container designed in this way.

According to the present invention, the ophthalmic solution contains (A) a nonionic surfactant and (B) a thickener, and the ophthalmic solution is designed so that the amount per drop is 5 to 25 μL. Thus, an eye drop having a high improvement effect on blurred vision can be provided. Therefore, in addition to the personal computer and the video game, it is possible to obtain a remarkable improvement effect for the blurring caused by VDT (Visual Display Terminal) work by a smartphone or a tablet terminal that has been increasing in number in recent years.
In addition, as another effect of the present invention, it is possible to provide an eye drop in which variation in the amount of drops per drop is suppressed. That is, the present inventors, in eye drops designed to contain a nonionic surfactant or a thickener and the amount of drops per drop is small, We found a new problem that the dispersion is likely to occur, but we found that the dispersion of the drop amount per drop of the eye drop was suppressed by including both the nonionic surfactant and the thickener. It was. With the eye drops of the present invention, an accurate amount of eye drops can be obtained even in small amounts, and a more reliable therapeutic effect can be obtained.
As another effect of the present invention, an eye drop having a high eye drop effect can be provided. That is, in the case of eye drops in which the amount per drop is small, the present inventors have difficulty in perceiving that one drop has entered the eye when actually instilling into the human eye. Although the new subject that a feeling was low was discovered, it discovered that an eye drop effective feeling improved by containing (A) nonionic surfactant and (B) thickener together. With the eye drop of the present invention, it is possible to surely feel whether one drop has entered the eye, improve the compliance, and obtain a more reliable therapeutic effect.

It is an example of the dripping nozzle with which the container filled with the eye drop of the present invention is attached. It is an example of the dripping nozzle with which the container filled with the eye drop of the present invention is attached.

1. Eye drops and eye drops in containers The present invention contains a nonionic surfactant as component (A) and a thickener as component (B), and is designed so that the amount per drop is 5 to 25 μL. It is characterized by being an eye drop.

In the present specification, the unit of content “%” means “w / v%” and “g / 100 mL”.
It is synonymous with.

In this specification, unless otherwise specified, the abbreviation “POE” represents polyoxyethylene, and the abbreviation “P
“OP” means polyoxypropylene, respectively.

(1) Nonionic surfactant [component (A)]
The eye drop of the present invention contains (A) a nonionic surfactant (hereinafter sometimes simply referred to as “component (A)”).
The nonionic surfactant used as the component (A) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. As such a nonionic surfactant, specifically, a polyoxyethylene (hereinafter also referred to as POE) -polyoxypropylene (hereinafter also referred to as POP) block copolymer (for example, Poloxamer 407, Poloxamer 235, Poloxamers such as poloxamer 188); POE-POP block copolymer adduct of ethylenediamine such as poloxamine; POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monooleate (polysorbate 80), POE sorbitan mono POE sorbitan fatty acid esters such as stearate (polysorbate 60) and POE sorbitan tristearate (polysorbate 65); POE hydrogenated castor oil 5, POE hydrogenated castor oil 10, POE hydrogenated castor oil 20 POE hydrogenated castor oil, such as POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE hydrogenated castor oil 100; POE castor oil, such as POE castor oil 3, POE castor oil 10, POE castor oil 35 POE (9) POE alkyl ethers such as lauryl ether; POE (20) POP (4) POE-POP alkyl ethers such as cetyl ether; POE (10) POE alkyl phenyl ethers such as nonyl phenyl ether; stearin Examples thereof include polyethylene glycol monostearate such as acid polyoxyl 40. The numbers in parentheses indicate the number of added moles.

Among these, from the viewpoint of further enhancing the effect of improving blurred vision, the effect of suppressing the variation in dripping amount, and the effect of improving the effectiveness of eye drops, preferably polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil , Poloxamers, and at least one nonionic surfactant selected from the group consisting of polyethylene glycol monostearate, more preferably poloxamer 407, poloxamer 188, polyoxyethylene castor oil 10, polyoxyethylene Castor oil 35, polysorbate 80, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, and polyoxyl 40 stearate, particularly preferably polysorbate 80 and polyoxyethylene hydrogenated castor oil 60 That.
These nonionic surfactants may be used alone or in any combination of two or more.

  In the eye drop of the present invention, the content of the component (A) is not particularly limited, and is appropriately set according to the type of the component (A), the use of the eye drop, and the like. As content of (A) component, it is preferable that the total content of (A) component is 0.0001 to 10% based on the total amount of the eye drop of the present invention, for example, 0.0001 to 5% Is more preferable, 0.001 to 1% is particularly preferable, and 0.005 to 0.5% is most preferable. The content of the component (A) is suitable from the viewpoint of further enhancing the blurred eye improving effect, the dripping amount variation suppressing effect, and the eye drop effective feeling improving effect.

(2) Thickener [Component (B)]
The eye drop of the present invention contains (B) a thickener (hereinafter sometimes simply referred to as “component (B)”).
The thickener used as component (B) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of such thickeners include vinyl thickeners (eg, polyvinyl alcohol (completely or partially saponified), polyvinylpyrrolidone (K25, K30, K90, etc.), carboxyvinyl polymer, etc.) Viscosity [eg, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose (2208, 2906, 2910, etc.), carboxymethylcellulose, carboxyethylcellulose, nitrocellulose or salts thereof], polyethylene glycol (Macrogol 300, Macrogol 400, macrogol 1500, macrogol 4000, etc.) or mucopolysaccharides (chondroitin sulfate, alginic acid, hyaluronic acid or their salts, etc.) And the like. Examples of the thickener salt include salts with inorganic bases, preferably alkali metal salts or alkaline earth metal salts, more preferably sodium salts, potassium salts, calcium salts, or magnesium salts. In particular, the sodium salt is preferred.

Among these, vinyl-based thickeners, cellulose-based thickeners, polyethylene glycols, and mucopolysaccharides are preferable from the viewpoint of further enhancing the blurring eye improvement effect, the dripping amount variation suppressing effect, and the ophthalmic efficacy improvement effect. More preferably, the vinyl thickener is polyvinyl alcohol, polyvinylpyrrolidone or carboxyvinyl polymer, and the cellulose thickener is methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose or a salt thereof. Polyethylene glycol is Macrogol 300 and Macrogol 400, and mucopolysaccharide is chondroitin sulfate or a salt thereof, alginic acid or a salt thereof, hyaluronic acid or a salt thereof. More preferred are carboxyvinyl polymer, hydroxypropylmethylcellulose, hydroxyethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, alginic acid, sodium hyaluronate, and particularly preferred are polyvinylpyrrolidone (K25, K90), carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose. (2208, 2906, 2910), and most preferred are polyvinylpyrrolidone (K25), carboxyvinyl polymer, hydroxyethylcellulose, and hydroxypropylmethylcellulose (2906).
Further, among these thickeners, those having a viscosity at 25 ° C. of the following values when dissolved in purified water so as to be 1.0 w / v% are preferable. In addition, the measurement of a viscosity follows the method as described in an Example.
Polyvinylpyrrolidone: preferably 0.1 to 5.0 mPa · s, more preferably 0.3 to 3.5 mPa · s, particularly preferably 0.5 to 2.0 mPa · s.
Carboxyvinyl polymer: preferably 1 to 30000 mPa · s, more preferably 200 to 5000 mPa · s, particularly preferably 400 to 3000 mPa · s.
Hydroxyethyl cellulose: preferably 1 to 5000 mPa · s, more preferably 5 to 1000 mPa · s, and particularly preferably 15 to 600 mPa · s.
Hydroxypropyl methylcellulose: preferably 1 to 3000 mPa · s, more preferably 50 to 800 mPa · s, particularly preferably 100 to 400 mPa · s.

In the eye drop of the present invention, the content of the component (B) is not particularly limited, and is appropriately determined according to the type of the component (B), the type and content of the component (A) to be used together, the use of the eye drop, and the like. Is set. As content of (B) component, it is preferable that the total content of (B) component is 0.01-10 w / v% on the basis of the total amount of the eye drop of this invention, for example, 0.01- It is more preferably 5 w / v%, particularly preferably 0.05 to 3%, and most preferably 0.1 to 1%. When the content ratio of the component (B) is within the above range, a blurred eye improving effect, a dripping amount variation suppressing effect, and a good eye drop effect feeling improving effect are obtained.
Moreover, as content rate of (B) component with respect to (A) component, the total content of a thickener is with respect to 1 mass part of total content of (A) component contained in the eye drop of this invention, for example. , 0.01 to 5000 parts by mass, more preferably 0.02 to 1000 parts by mass, and particularly preferably 0.2 to 200 parts by mass. The content ratio of the thickener is suitable from the viewpoint of enhancing the blurred eye improving effect, the dripping amount variation suppressing effect, and the eye drop effective feeling improving effect.

(3) Terpenoid compounds [component (C)]
The eye drop of the present invention preferably further contains a terpenoid compound (hereinafter sometimes referred to as “component (C)”). By blending the component (C) with the eye drop containing the component (A) and the component (B), it is possible to further enhance the blurred eye improving effect, the dripping amount variation suppressing effect, and the eye drop effective feeling improving effect.

The terpenoid compound used as the component (C) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of such terpenoid compounds include menthol, camphor, borneol, geraniol, cineole, citronellol, menthone, carvone, anethole, eugenol, limonene, linalool, linalyl acetate, and derivatives thereof. These compounds may be d-form, l-form or dl-form. In the present invention, an essential oil containing the above compound may be used as the terpenoid compound. Examples of such essential oils include eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, and rose oil. These terpenoid compounds may be used alone or in any combination of two or more.
Among these, from the viewpoint of further enhancing the effect of improving blurred vision, the effect of suppressing variation in dripping amount, and the effect of improving the effectiveness of eye drops, dl-menthol, l-menthol, dl-camphor, d-camphor, d-borneol And at least one selected from the group consisting of geraniol, and preferred essential oils containing these include cool mint oil, peppermint oil, peppermint oil, camphor oil and the like. More preferred are dl-menthol, l-menthol, dl-camphor, d-camphor, d-borneol, geraniol, particularly preferably l-menthol, d-camphor, dl-camphor, most preferably l- Mentor is mentioned.

In the eye drop of the present invention, the content of the component (C) is not particularly limited, the type of the component (C), the type and content of the component (A) and the component (B) used together, the use of the eye drop, It is appropriately set according to the formulation form, usage method and the like. As content of (C) component, it is preferable that the total content of (C) component is 0.0001-0.2 w / v% on the basis of the total amount of the eye drop of this invention, for example, 0 More preferably, it is .0005 to 0.1 w / v%, and particularly preferably 0.001 to 0.08 w / v%. In addition, when using the essential oil containing a terpenoid compound, it can set so that the terpenoid compound in the essential oil contained in an eye drop may satisfy | fill the said content. The content of the terpenoid compound is suitable from the viewpoints of improving the blurred eye improvement effect, the dripping amount variation suppressing effect, and the eye drop effectiveness.
In addition, as the content ratio of the component (C) to the component (A), for example, the total content of the terpenoid compound is 1 part by mass of the total content of the component (A) contained in the eye drop of the present invention. The amount is preferably 0.0005 to 100 parts by mass, more preferably 0.001 to 20 parts by mass, and particularly preferably 0.002 to 16 parts by mass. The content ratio of the terpenoid is preferable from the viewpoint of improving the blurred eye improvement effect, the dripping amount variation suppressing effect, and the eye drop effective feeling.

(4) Other ingredients [arbitrary ingredients]
In addition to the components (A), (B), and (C), the eye drops of the present invention can contain active ingredients (pharmacologically active ingredients, physiologically active ingredients, etc.) that are widely used in eye drops. . The kind of such component is not particularly limited, and examples thereof include an anti-inflammatory component or an astringent component, an antiallergic component, a vitamin, an amino acid, an antibacterial component or a bactericidal component. Examples of the pharmacologically active component and physiologically active component suitable in the present invention include the following components.

Decongestant: Tetrahydrozoline, naphazoline, epinephrine, ephedrine, methylephedrine, etc.
Eye muscle modulator component: For example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically, neostigmine methyl sulfate, tropicamide, atropine sulfate helenien, and the like.
Anti-inflammatory component or astringent component: zinc sulfate, zinc lactate, allantoin, epsilon-aminocaproic acid, lysozyme chloride, pranoprofen, sodium azulenesulfonate, dipotassium glycyrrhizinate, bromfenac sodium, berberine chloride, berberine sulfate, etc. .

  Antihistamine component or antiallergic agent component: acitazanolast, diphenhydramine hydrochloride, chlorpheniramine maleate, tranilast, sodium cromoglycate, pemirolast potassium and the like.

  Vitamins: Retinol acetate, retinol palmitate, pyridoxine hydrochloride, flavin adenine dinucleotide sodium, cyanocobalamin, panthenol, calcium pantothenate, sodium pantothenate, tocopherol acetate, etc.

  Amino acids: For example, aminoethylsulfonic acid (taurine), potassium aspartate, magnesium aspartate, magnesium / potassium aspartate mixture, epsilon-aminocaproic acid and the like. These may be d-form, l-form or dl-form.

  Antibacterial component or bactericidal component: alkylpolyaminoethylglycine, sulfamethoxazole, sulfisoxazole, sulfamethoxazole sodium, sulfisomidine sodium and the like.

  In addition, the eye drop of the present invention is appropriately selected from various components and additives according to a conventional method according to its use and form as long as the effects of the invention are not impaired, and one or more of them are used in combination. Can be contained. As those components or additives, for example, carriers (aqueous solvent, aqueous or oily base, etc.) generally used for the preparation of solutions, preservatives, bactericides or antibacterial agents, pH adjusters, tonicity agents And various additives such as chelating agents, buffering agents and stabilizers.

  Carrier: For example, water, aqueous solvent such as water-containing ethanol.

  Preservatives, bactericides or antibacterial agents: polydronium chloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, Methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide or its hydrochloride, etc.).

  pH adjusting agent: hydrochloric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine, sulfuric acid, phosphoric acid, diethanolamine and the like.

  Isotonizing agents: potassium chloride, sodium chloride, glycerin, propylene glycol and the like.

  Chelating agent: sodium edetate, citric acid, or hydrates thereof.

  Buffer: citrate buffer, acetate buffer, carbonate buffer, borate buffer, phosphate buffer, Tris-HCl buffer, etc. Specifically, citric acid, sodium citrate, acetic acid, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, boric acid, borax, phosphoric acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, phosphoric acid Potassium dihydrogen, etc.

Stabilizer: Dibutylhydroxytoluene, trometamol, sodium bisulfite, sodium sulfite and the like.
Vegetable oil: Sesame oil, castor oil, etc.

(5) Physical Properties of Eye Drops The pH of the eye drop of the present invention is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable range. As pH of eyedrops, it is preferable that it is 4.0-9.5, for example, it is more preferable that it is 5.0-9.0, and it is still more preferable that it is 5.5-8.5.
Further, the osmotic pressure of the eye drop of the present invention is not particularly limited as long as it is within the range allowed by the living body. The osmotic pressure ratio of the eye drop is, for example, preferably 0.5 to 5.0, more preferably 0.6 to 3.0, and still more preferably 0.7 to 2.0. 0.9 to 1.55 is particularly preferable. The osmotic pressure can be adjusted by a method known in the art using an inorganic salt, a polyhydric alcohol, a sugar alcohol, a sugar, or the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 16th revised Japanese Pharmacopoeia. Measure with reference to (freezing point depression method). In addition, about the standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution), after drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500-650 degreeC for 40-50 minutes, it is in a desiccator (silica gel). It is allowed to cool, and 0.900 g is accurately weighed and dissolved in purified water to prepare exactly 100 mL, or a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution) can be used. .
The viscosity of the eye drop of the present invention containing the components described above is preferably 1.1 to 9000 mPa · s.
In the present invention, selection of conditions such as the rotor and rotation speed is based on the instruction manual of the apparatus, and the viscosity at 25 ° C. is measured.
In the present invention, the viscosity is measured in accordance with the viscosity measuring method described in the 16th revised Japanese Pharmacopoeia general test method. When the viscosity at 25 ° C. is 100 mPa · s or more, (2) single cylindrical rotation When the viscosity at 25 ° C. is less than 100 mPa · s, (3) a cone-plate rotational viscometer (cone plate viscometer) is used. In the present invention, selection of conditions such as the rotor and rotation speed is based on the instruction manual of the apparatus, and the viscosity at 25 ° C. is measured.

(6) One drop volume of eye drop The eye drop of the present invention is designed so that the drop volume per drop is 5 to 25 μL. Designed so that the amount of the eyedrop per drop is 5 to 25 μL, which is within the capacity of the conjunctival sac, so that the overflowing eyedrop adheres around the eye, resulting from the component (B) Thus, there is no risk that the eyes will stick around and the user will feel uncomfortable.
In addition, the eye drop of the present invention is preferably designed so that the drop amount per drop is 7 to 20 μL, and more preferably 9 to 15 μL.

(7) Eye Drop Container, etc. The eye drop of the present invention is preferably filled in a container having an internal volume of 4 to 30 mL, more preferably 5 to 20 mL. 6 It is particularly preferable that the container is filled with 10 mL.
When the internal volume of the container filled with the eye drop of the present invention is within the above range, even if the amount of one drop is small, it is easy to instill and the effect of the present invention can be exhibited more remarkably. Further, as will be described later, even when instillation is performed using a small-diameter eye drop nozzle, it is particularly preferable from the viewpoint of suppressing variation in the amount of dripping and making the user feel the eye drop effective. As such an eye drop, a multi-dose type eye drop, that is, an eye drop that is used several times or more after the product is once opened is preferable.

As an example of the dropping nozzle attached to the container filled with the eye drop of the present invention, those having the shape shown in FIGS. As a dropping nozzle attached to a container filled with the eye drop of the present invention, the inner diameter D1 at the dropping port is preferably less than 1.5 mm, more preferably 0.01 to 1.0 mm, It is particularly preferably 0.05 to 0.8 mm, further particularly preferably 0.1 to 0.5 mm, and most preferably 0.1 to 0.4 mm. The dropping port refers to an outlet portion where droplets are formed when the eye drop is filled in the container and the nozzle is attached and then in an open state.
Further, the outer diameter of the dropping nozzle attached to the container filled with the eye drop of the present invention is appropriately set according to the shape, material, purpose, etc. of the nozzle, and cannot be generally defined, for example, 8 mm The following is preferable, more preferably 0.1 to 5 mm, particularly preferably 0.3 to 3 mm, still more preferably 0.5 to 2 mm, and more preferably 0.5 to 1.5 mm. Most preferred. The outer diameter of the dropping nozzle in the present invention indicates the outer diameter of the pouring tube body near the dropping port, and the tip (dropping port) of the nozzle may be rounded.

The said range in the nozzle aperture of the container filled with the eyedrops of this invention is suitable in order to make the dripping amount per drop into 5-25 microliters.
By adopting such a nozzle shape, it becomes easy to set the drop amount per one drop of the eye drop to 5 to 25 μL. For example, the eye drop is efficiently used so that the drop amount per drop is 15 μL. Therefore, the effects of the present invention including the above-described effect of improving the blur can be remarkably exhibited.
The nozzle may have either a structure formed separately from the container body or a structure in which the nozzle and the container body are integrally formed (for example, a one-time-use type eye drop).

The container filled with the eye drop of the present invention is preferably made of plastic. The constituent material of the plastic container is not particularly limited. For example, any one of polyesters such as polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate, polyarylate, polycarbonate, polyethylene, polypropylene, polyimide, and elastomer, A copolymer or a mixture of two or more of these may be mentioned. In particular, polyethylene terephthalate, polyarylate, polyethylene naphthalate, a copolymer thereof, or a mixture of two or more of these is preferable from the viewpoint of easily exerting the effect of the present invention by adjusting the extrusion and the like. Particularly, a container made of polyethylene terephthalate. Is preferred.
In the present invention, for example, a container made of polyethylene terephthalate is not particularly limited as long as polyethylene terephthalate is contained in the constituent material of the container, but the polyethylene terephthalate is based on the total weight of the constituent material of the container. Is preferably 50 w / w% or more.
The eye drop of the present invention may be filled in a transparent container (a container having transparency that does not interfere with the observation of foreign matter) containing such a material as a main material, or in a light-shielded container. May be. The light shielding may be performed, for example, by adding a colorant to the transparent container material described above, or may be shielded by covering the container with a shrink film or an outer box.
The constituent material of the nozzle is preferably made of plastic, for example. From the viewpoint of further improving the liquid drop of the eye drop of the present invention and suppressing variation in the dripping amount, a nozzle including polyethylene, polypropylene, polybutylene terephthalate or elastomer as a constituent material is preferable. Examples of the type of polyethylene include high-density polyethylene and low-density polyethylene, and among them, a nozzle including low-density polyethylene as a constituent material is preferable.

(8) Physical properties of eye drop in container It is preferable that the eye drop of the present invention is in a container suitable for dropping a predetermined amount of one drop. The squeeze force of the ophthalmic solution in a container is preferably 0.5 to 12N, more preferably 1 to 10N, and particularly preferably 1.5 to 8N. The squeeze force indicates a force that pushes a container necessary for dropping one drop of eye drops. When the squeeze force of the eye drop in a container of the present invention is within the above range, the effect of suppressing variation in the amount of dripping and the effect of improving the eye drop effectiveness can be more remarkably exhibited. The squeeze force is measured according to the method described in the examples.
Further, the displacement of the container when the eye drop in the container of the present invention is dropped is preferably 0.01 to 2.0 mm, more preferably 0.05 to 1.0 mm, and 0.05 to 0. 0.5 mm is particularly preferable, and 0.06 to 0.3 mm is most preferable.
The displacement of the container when the eye drop in the container is dropped is the displacement of the container necessary for dropping one drop of the eye drop. When the displacement of the container at the time of dropping of the eye drop in the container of the present invention is within the above range, the effect of suppressing variation in the amount of dripping and the effect of improving the eye drop effectiveness can be more remarkably exhibited.
The measurement of the displacement of the container at the time of dripping is performed according to the method as described in an Example.

(9) Use of eye drops In addition to general eye drops, the eye drops according to the present invention include antibacterial eye drops, artificial tears, and eye drops that can be applied while wearing contact lenses.
The eye drops that can be instilled while wearing the contact lens can be applied to all contact lenses including hard contact lenses and soft contact lenses. Soft contact lenses include both ionic and non-ionic, and include silicone hydrogel contact lenses (hereinafter abbreviated as SHCL) and non-silicone hydrogel contact lenses (silicone hydrogel lenses). Including both soft contact lenses).
(10) Eye drop method The drop method of the eye drop of the present invention is not particularly limited, and the eye drop can be applied from any angle depending on the shape of the eye drop container, the nozzle, the purpose of use, and the like. It is preferable that the dropping port is dropped directly below from the viewpoint of achieving the effect of suppressing variation in the dropping amount of the present invention more remarkably.

2. The present invention provides an eye drop containing a nonionic surfactant as a component (A) and a thickener as a component (B), and one drop of the eye drop There is also provided a method of designing the eye drop so that the amount per drop is 5 to 25 μL, and imparting a haze improvement effect to the eye drop.
In the above method, as long as the component (A) and the component (B) coexist, they may be added simultaneously or separately, and the order thereof is not particularly limited. Component (A) to be used, type of component (B), their content (or blending amount), their content ratio, drop amount per drop, other types of component to be blended, content (or blending amount) ), The preparation form of the eye drop, the type of container, the type of nozzle, the combination thereof, the method of implementation, and the like are the same as those in “1. Eye drop”.
In the present specification, whether or not the blur is improved can be determined by a method described in Examples described later.

3.1 Droplet Variation Control Method As described above, the eye drop of the present invention contains (A) a nonionic surfactant and (B) a thickener, and a drop amount per drop is 5. By being designed to be ˜25 μL, it is possible to suppress variations in the amount of one drop.
Therefore, the present invention further comprises, from another viewpoint, an ophthalmic solution containing a nonionic surfactant as the component (A) and a thickener as the component (B), and the amount of the eyedrop per one drop. Also provided is a method of designing the eye drop so as to be 5 to 25 μL and suppressing variations in the amount of one drop.
In the above method, as long as the component (A) and the component (B) coexist, they may be added simultaneously or separately, and the order thereof is not particularly limited. Component (A) to be used, type of component (B), their content (or blending amount), their content ratio, drop amount per drop, other types of component to be blended, content (or blending amount) ), The preparation form of the eye drop, the type of container, the type of nozzle, the combination thereof, the method of implementation, and the like are the same as those in “1. Eye drop”.
In addition, in this specification, it can be determined by the method as described in the below-mentioned Example whether the dispersion | variation in the amount of 1 drop of eyedrops is suppressed.

4). Method for Improving Eye Drop Effectiveness As described above, the eye drop of the present invention contains (A) a nonionic surfactant and (B) a thickener, and the drop amount per drop is 5 to 25 μL. It is possible to improve the effectiveness of eye drops.
Accordingly, the present invention, from yet another point of view, contains a nonionic surfactant as the component (A) and a thickener as the component (B) in the eye drop, and per eye drop of the eye drop There is also provided a method for improving the effectiveness of eye drops, in which the eye drops are designed so that the dripping amount is 5 to 25 μL.
In the above method, as long as the component (A) and the component (B) coexist, they may be added simultaneously or separately, and the order thereof is not particularly limited. Component (A) to be used, type of component (B), their content (or blending amount), their content ratio, drop amount per drop, other types of component to be blended, content (or blending amount) ), The preparation form of the eye drop, the type of container, the type of nozzle, the combination thereof, the method of implementation, and the like are the same as those in “1. Eye drop”.
In the present specification, whether or not the eye drop effectiveness is improved can be determined by a method described in Examples described later.

Hereinafter, the present invention will be described in detail with reference to Examples and Test Examples, but the present invention is not limited to these Examples and the like.
Moreover, the average dripping amount (μL) was calculated by calculating the average dripping amount (mg) in each eye drop in each container and setting the specific gravity as 1. As a method for measuring the average drop amount (mg), the drop port of the ophthalmic nozzle in the container was dropped almost vertically downward, the drop weight was measured for each drop, and this operation was repeated 20 times. Calculated from the values.
The unit of composition in each table is w / v%.

(1) Preparation of sample Each eye drop having the composition shown in Tables 1 to 5 was prepared by the following method. That is, under stirring, a thickener such as carboxyvinyl polymer was added and dispersed in purified water, and then components other than the pH adjuster (sodium hydroxide or hydrochloric acid) were added and dissolved by stirring. Furthermore, after adjusting pH using sodium hydroxide or hydrochloric acid, an appropriate amount of purified water was added to prepare a predetermined concentration.
Viscosity is measured for the prepared eye drops, and squeeze force measurement, measurement of container displacement at the time of dripping, blurred eye test, dripping amount of eye drops in containers filled with eye drops in a predetermined container. A dispersion test and an eye drop effect test were performed.

(2) Physical property measurement method (2-1) Viscosity measurement The viscosity of each eye drop was measured by the following method.
Those having a viscosity at 25 ° C. of 100 mPa · s or more are described in “16th revised Japanese Pharmacopoeia General Test Method Viscosity Measurement Method 2 Method Rotary Viscometer Method” (2) Single Cylindrical Rotational Viscometer (Brook Based on the test method of “field type viscometer”, the viscosity at 25 ° C. was measured under the following conditions.

Measuring device, rotation speed, rotor No. 1 w / v% aqueous solution of a thickening agent for a set time or less: carboxyvinyl polymer, hydroxyethyl cellulose (Test 1, Test 5), hydroxypropyl methylcellulose 2906:
Measuring device_TV-10M, rotation speed_12 rpm, rotor No. _M2, viscosity after 1 minute of measurement time

Those with a viscosity at 25 ° C. of less than 100 mPa · s are described in the 16th revised Japanese Pharmacopoeia General Test Method Viscosity Measurement Method Second Method Rotary Viscometer Method “(3) Cone-Plate Rotational Viscometer (Cone Plate The viscosity at 25 ° C. was measured under the following conditions in accordance with the test method “type viscometer”.

Measuring device, rotation speed, rotor No. And set time / prescription example 1, prescription example 5-B, 5-C, 5-D:
Measuring apparatus_RC-550, rotation speed_10 rpm, rotor_standard cone rotor (1 ° 34 ′ × R24), set time_viscosity after 3 minutes, 1 w / v% aqueous solution of hydroxyethylcellulose (test 4):
Measuring device_RC-550, rotation speed_20 rpm, rotor_standard cone rotor (1 ° 34 ′ × R24), set time_viscosity after 3 minutes / Prescription Example 5-A, 1% w / v aqueous solution of polyvinylpyrrolidone K25 :
Measuring device_RC-550, rotation speed_100rpm, rotor_standard cone rotor (1 ° 34 'x R24), set time_viscosity after 3 minutes

(2-2) Squeeze force measurement The squeeze force of each eye drop in each container was measured by the following method.
Two drops of the eye drop in a container to be tested were dropped with the dropping port directed directly below in an unused state after filling. Next, the ophthalmic solution in a container was fixed by pressing with a finger on a vertical wall surface with the dripping port directed directly below. Next, squeeze when dropping one drop by applying pressure to the side of the container with a 5 mm diameter flat jig attached to the tip of a digital push-pull gauge (CPU GAUGE 9520A, manufactured by Aiko Engineering Co., Ltd.) The force (N) was measured. The measurement was carried out 10 times (for 10 drops), and the average was obtained.

(2-3) Measurement of container displacement at the time of dropping The container displacement at the time of dropping each container-containing eye drop was measured by the following method.
The relationship between displacement and squeeze force of the eye drop in a container to be tested was determined using an autograph (product name: AUTO GRAPH AGS-X 5kN TRAPEZIUM (manufactured by SHIMADZU)) in an unused state after filling. Thereafter, the displacement value of the container corresponding to the squeeze force determined in advance according to the method (2-2) was determined.
The autograph measurement conditions are as follows.
・ Cross head speed: 100mm / min
・ Jig: Φ5mm

(3) Reagent A thickener having a viscosity at 25 ° C. of the following value when dissolved in purified water so as to be 1.0 w / v% was used. (Measurement conditions were based on the method described in (2) Physical property measurement method (2-1) Viscosity measurement)
Carboxyvinyl polymer: 1911 mPa · s
Hydroxyethyl cellulose (Test 1, Test 5): 481.0 mPa · s
Hydroxyethyl cellulose (Test 4): 18.6 mPa · s
Hydroxypropyl methylcellulose 2906: 258.5 mPa · s
Polyvinylpyrrolidone K25: 1.2 mPa · s

[Test 1: Blunt eye improvement effect test]
(Test method)
Formulation examples (eye drops) having the compositions shown in Table 1 were prepared, and 6 mL and 13 mL of polyethylene terephthalate eye drop containers having an internal volume of 7.7 mL and 14.2 mL were filled, respectively, and polyethylene nozzles were attached to these containers. As a nozzle made of polyethylene, a container having an internal volume of 7.7 mL is (i) a nozzle suitable for dropping 5 to 15 μL (inner diameter 0.3 mm, outer diameter 0.9 mm, hereinafter referred to as nozzle (i). In the container of Example 1) and an internal volume of 14.2 mL, (ii) a nozzle suitable for dropping 30 to 50 μL (inner diameter of 2 mm, outer diameter of 5.5 mm, hereinafter referred to as nozzle (ii)) In some cases; Comparative Example 1) was used. Using this ophthalmic solution in a container, a test for improving the blurring effect was performed.
First, the flicker value was measured after applying strain to the eyes by performing VDT work for 1 hour for 3 subjects who were easily obscured (pre-dose flicker value).
Next, the eye drop of Example 1 was instilled into both eyes drop by drop, and the flicker value was determined after 1 minute (Example 1). Further, in the same procedure, the eye drop of Comparative Example 1 was instilled into both eyes one by one, and then a flicker value was determined after 1 minute (Comparative Example 1). From the measured flicker value, the flicker value improvement rate was obtained by the following formula (I).
The flicker value is a critical frequency at which blinking cannot be identified by the naked eye when the blinking frequency of the blinking light is gradually increased. Using the flicker value as an index, it is possible to measure blurring of eyes and deterioration of perceptual function. That is, the improvement of the flicker value is an index for improvement of blurring of eyes and eye strain.

In this test, the flicker value was measured with the following apparatus and conditions.
Device name: Rugken digital flicker value measuring instrument RDF-1 (manufactured by Shibata Kagaku Co., Ltd.)
Illuminance: Set to the illuminance that is easy for the measurer to see Distance: Set to the position where the measurer is easy to see (the position where the letter “K” is most clearly visible) SCAN knob (initial flicker frequency to be lowered): 60 Hz
MANU-AUTO: set to AUTO From the measured flicker value, a blur improvement value (flicker value improvement rate) is obtained by the following formula.

Table 1 shows the average of the results of three subjects. As a result, it was confirmed that in all of the three test subjects, the flicker value improvement rate was significantly increased in Example 1 as compared with Comparative Example 1.
From the above results, it was confirmed that the eye drop of the present invention is remarkably excellent in the effect of improving blurring and highly useful compared to the case of using the conventional drop amount.

[Test 2] Evaluation of variation in dripping amount 1
Each formulation example (eye drops) was prepared according to the composition shown in Table 2, and 6 mL of a polyethylene terephthalate eye drop container having an internal volume of 7.7 mL was filled, and a polyethylene nozzle was attached to the container. As the polyethylene nozzle, (i) a nozzle suitable for dropping 5 to 15 μL (inner diameter 0.3 mm, outer diameter 0.9 mm, hereinafter sometimes referred to as nozzle (i)), and (iii) A nozzle suitable for dropping 30 to 50 μL (inner diameter 2 mm, outer diameter 6 mm, hereinafter sometimes referred to as nozzle (iii)) was used. The ophthalmic solution in a container was dropped with the nozzle drop opening facing substantially vertically downward, and the drop weight was measured for each drop. From the average drop amount (AVG: mg) and standard deviation (SD: mg) determined by repeating this operation 20 times, the drop amount variation (variation coefficient CV:%) was calculated by the following formula (II).

* The squeeze force (N) in each container eye drop was as follows.
Example 2-1 1.6
Example 2-2 1.5
* Displacement (mm) of the container at the time of dropping in each container-containing eye drop was as follows.
Example 2-1 0.08
Example 2-2 0.06

Compared to the case where each of the solutions containing either hydroxypropylmethylcellulose 2906 (HPMC) or polysorbate 80 was filled and then dropped with the nozzle (iii) attached (Reference Examples 2-1 and 2-2). When the nozzle (i) was mounted (Comparative Examples 2-1 and 2-2), it was confirmed that the variation was remarkably increased.
However, when both HPMC and polysorbate 80 were blended (Example 2-1), it was surprisingly found that the variation in the dripping amount was improved.
Further, in the case of ophthalmic solution containing 1-menthol in polysorbate 80 and equipped with nozzle (i) (Comparative Example 2-3), compared with the case of polysorbate 80 alone (Comparative Example 2-1). It was confirmed that the dispersion of the dripping amount increased. However, surprisingly, it was confirmed that when l-menthol was blended with HPMC and polysorbate 80, the variation in dripping amount was remarkably improved (Example 2-2).

[Test 3] Evaluation of variation in dripping amount 2
Each formulation example (eye drops) was prepared according to the composition shown in Table 3, and 6 mL of a polyethylene terephthalate eye drop container having an internal volume of 7.7 mL was filled, and a polyethylene nozzle was attached to the container. As the polyethylene nozzle, nozzle (i) and nozzle (iii) were used. The ophthalmic solution in a container was dropped with the nozzle drop opening facing substantially vertically downward, and the drop weight was measured for each drop. From the average dripping amount (AVG: mg) and the standard deviation (SD: mg) obtained by repeating this operation 20 times, variation in the dripping amount (variation coefficient CV:%) was calculated by the formula (II). Further, using the following formula (III), the variation (%) in the drop amount of Examples and Reference Examples for Comparative Example 3-1 was calculated. The calculation results are also shown in Table 3.

After filling a solution containing polyoxyethylene hydrogenated castor oil 60 as a nonionic surfactant and then dropping with nozzle (iii) attached (reference example 3-1), nozzle (i ) Was attached (Comparative Example 3-1), it was confirmed that the variation increased markedly.
However, when the carboxyvinyl polymer, hydroxyethyl cellulose, or polyvinylpyrrolidone K25 is contained together with the polyoxyethylene hydrogenated castor oil 60 (Example 3-1, Example 3-3, Example 3-4), it is surprising. In particular, it was confirmed that variation in the amount of dripping was improved. Moreover, when polyoxyethylene hydrogenated castor oil 60, carboxy vinyl polymer, or polyvinyl pyrrolidone K25 was contained, and when 1-menthol was further contained, it was confirmed that the variation in dripping amount was further remarkably improved. (Example 3-2, Example 3-5).

[Test 4] Variation evaluation of dripping amount 3
Each formulation example (eye drops) was prepared according to the composition shown in Table 4, filled in 6 mL of a polyethylene terephthalate eye drop container having an internal volume of 7.7 mL, and a polyethylene nozzle was attached to the container. As the polyethylene nozzle, nozzle (i) and nozzle (iii) were used. The ophthalmic solution in a container was dropped with the nozzle drop opening facing substantially vertically downward, and the drop weight was measured for each drop. From the average dripping amount (AVG: mg) and the standard deviation (SD: mg) obtained by repeating this operation 20 times, variation in the dripping amount (variation coefficient CV:%) was calculated by the formula (II). Furthermore, the variation (%) of the drop amount of the reference example and the example for the comparative example 4-1 was calculated using the formula (III). The calculation results are also shown in Table 4.

In the case where the nozzle (i) is mounted compared to the case where the nozzle (iii) is mounted and dropped after filling a solution containing polysorbate 80 as a nonionic surfactant (Reference Example 4-1) In (Comparative Example 4-1), it was confirmed that the variation significantly increased.
However, when carboxyvinyl polymer, hydroxyethyl cellulose and polyvinylpyrrolidone K25, and l-menthol were contained together with polysorbate 80 (Examples 4-1, 4-2, and 4-3), it was surprising. In particular, it was confirmed that the variation in the dripping amount was remarkably improved.

[Test 5: Effectiveness test when instilled]
Eye drops having the composition shown in Table 5 were prepared, and 6 mL and 13 mL of polyethylene terephthalate eye drop containers having an internal volume of 7.7 mL and 14.2 mL were filled, respectively, and a polyethylene nozzle was attached to the container. As a polyethylene nozzle, nozzle (i) was used for a container having an internal volume of 7.7 mL, and nozzle (ii) was used for a container having an internal volume of 14.2 mL.
This eye drop in a container was instilled once (one drop) by the subject himself, and the eye drop effective feeling at the time of eye drop was measured. The effect of eye drops indicates a feeling that allows the user to be aware that the dropped eye drops have entered the eye when he / she drops. More specifically, VAS (Visual Analog Scale) method in which 10 subjects were blindly instilled with a predetermined amount of the test solution and 10 when the instillation could be clearly recognized, and 0 when no instillation could be recognized at all. Was used to determine the eye drop effectiveness score.

  Moreover, the average dripping amount (μL) in each eye drop in each container was determined in advance.

* The squeeze force (N) in each container eye drop was as follows.
Example 5-1 3.5
Example 5-2 2.9
Example 5-3 2.5
* Displacement (mm) of the container at the time of dropping in each container-containing eye drop was as follows.
Example 5-1 0.15
Example 5-2 0.12
Example 5-3 0.12

Table 5 also shows the effectiveness score.
When Reference Example 5-1 in which Prescription Example 5-A was filled and nozzle (ii) was mounted was instilled, the effectiveness of eyedrops was 10 in all subjects. On the other hand, in the case of Comparative Example 5-1, in which the nozzle (i) was mounted, the effectiveness score was low and almost no eye drop effect was felt, but surprisingly, hydroxyethyl cellulose and polysorbate 80 were combined. (Example 5-1), it was confirmed that the ophthalmic efficacy score was remarkably improved and the ophthalmic efficacy was obtained even when the amount of dripping was small.
Moreover, when menthol was further mix | blended with the hydroxyethyl cellulose and the polysorbate 80 (Example 5-2, Example 5-3), it was confirmed that an eye drop effective feeling improves further notably.

[Test 6] Evaluation of variation in dripping amount 4
Each formulation example (eye drops) was prepared according to the composition shown in Table 6, filled in 6 mL of a polyethylene terephthalate eye drop container having an internal volume of 7.7 mL, and a polyethylene nozzle was attached to the container. Nozzle (i) was used as a polyethylene nozzle. The ophthalmic solution in a container was dropped with the nozzle drop opening facing substantially vertically downward, and the drop weight was measured for each drop. From the average dripping amount (AVG: mg) and the standard deviation (SD: mg) obtained by repeating this operation 20 times, variation in the dripping amount (variation coefficient CV:%) was calculated by the formula (II). Furthermore, variation (%) with respect to the corresponding comparative example was calculated using the formula (III). The calculation results are also shown in Table 6. The corresponding comparative examples are Example 6-1-1, Example 6-1-2 for Comparative Example 6-1, Example 6-2-1, Example 6-2-2 for Comparative Example 6. -2.

* The squeeze force (N) in each container eye drop was as follows.
Example 6-1-1 3.0
Example 6-1-2 2.2
Example 6-2-1 2.1
Example 6-2-2 1.7
* Displacement (mm) of the container at the time of dropping in each container-containing eye drop was as follows.
Example 6-1-1 0.10
Example 6-1-2 0.09
Example 6-2-1 0.09
Example 6-2-2 0.07

  When the carboxyvinyl polymer or polyvinylpyrrolidone K25 is contained together with the polyoxyethylene hydrogenated castor oil 60 (Example 6-1-1, Example 6-2-1), surprisingly, there is a variation in the amount of dripping. It was confirmed that it improved. In addition, when polyoxyethylene hydrogenated castor oil 60, carboxyvinyl polymer, or polyvinylpyrrolidone K25 is contained, and further l-menthol, dl-camphor, geraniol, or bergamot oil is contained, variation in the dripping amount varies. Furthermore, it was confirmed that it improved remarkably (Examples 6-1-2 and 6-2-2).

[Formulation example]
Preparation examples (eye drops) shown in Tables 7 and 8, and Tables 9 and 10 were prepared and filled in a predetermined container and then mounted with a predetermined nozzle. did.
Formulation Examples 1 to 13: After filling Formulation Formulation Examples 1 to 13 in a container with an internal volume of 6 mL, a nozzle having an inner diameter of 0.1 mm and an outer diameter of 0.4 mm attached to the dripping port (dropping) (Amount: 9μL)
Formulation Examples 14 to 26: After filling Formulation Formulation Examples 1 to 13 in a container with an internal volume of 8 mL, a nozzle having an inner diameter of 0.3 mm and an outer diameter of 1.0 mm attached to the dropping port (dropping) (Amount: 15 μL)
Formulation Examples 27 to 39: After filling Formulation Formulation Examples 1 to 13 in a container having an internal volume of 10 mL, a nozzle having an inner diameter of 0.5 mm and an outer diameter of 1.2 mm attached to the dropping port (dropping) (Amount: 18 μL)

表１０へ続く

Continued to Table 10

  The eye drop of the present invention can effectively improve the blurred eye, and can suppress the variation of the drop amount and improve the user's eye drop effect when the drop is applied in a small amount. Therefore, the eye drop of the present invention is highly practical and has a good feeling of use.

Claims (9)

A (A) nonionic surfactant and (B) eye drops containing a thickener, dropping amount per one drop Ri 5~25μL der, wherein (B) the thickener, hydroxypropyl An eye drop which is at least one selected from the group consisting of methyl cellulose and hydroxyethyl cellulose .   The eye drop according to claim 1 filled in a container having an internal volume of 4 to 30 mL.   The eye drop according to claim 1 or 2, filled in a container having a nozzle having an inner diameter of less than 1.5 mm at the dropping port.   The nonionic surfactant is at least one selected from the group consisting of polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, poloxamers, and polyethylene glycol monostearate. The ophthalmic solution according to any one of claims 1 to 3. The ophthalmic solution according to any one of claims 1 to 4 , further comprising (C) a terpenoid compound. The eye drop according to claim 5 , wherein the terpenoid compound is at least one selected from the group consisting of dl-menthol, 1-menthol, dl-camphor, d-camphor, d-borneol, and geraniol. The eye drop in a container according to claim 5 or 6, wherein the content of the terpenoid compound is 0.0001 to 0.2 w / v%. The eye drop contains (A) a nonionic surfactant and (B) a thickener, and the (B) thickener is at least one selected from the group consisting of hydroxypropylmethylcellulose and hydroxyethylcellulose. And the method of providing a blurring eye improvement effect to the eye drop characterized by designing so that the dripping amount per drop of this eye drop may be 5-25 microliters. The eye drop contains (A) a nonionic surfactant and (B) a thickener, and the (B) thickener is at least one selected from the group consisting of hydroxypropylmethylcellulose and hydroxyethylcellulose. And the method of suppressing the dispersion | variation in the amount of 1 drop of eye drops characterized by designing so that the drop volume per 1 drop of this eye drop may be 5-25 microliters.

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