TW201815397A - Ophthalmic agent and ophthalmologic drug - Google Patents

Abstract

The present invention addresses the problem of providing an ophthalmic agent that can be used to ameliorate at least one symptom selected from the group consisting of: eye discharge, dull and heavy feeling, eyestrain, blurred vision, red eyes, photophobia, and itchy eyes. Provided is an ophthalmic agent containing (A) hydroxypropyl methylcellulose and (B) vitamin E.

Description

Ophthalmic agents and ophthalmic drugs

The invention relates to an ophthalmic agent and an ophthalmic agent.

Eye fat (also known as "eye feces") is caused by conjunctival inflammation and excessive secretion of mucous substances (mucin) on the surface of the eye. The exudate, which is the source of ocular fat, exudates from the dilated conjunctival blood vessels and reaches the ocular surface through the conjunctival epithelium. Eyelids are made by mixing mucus (mucin) or epithelial cells. Mucin is secreted by conjunctival goblet cells. Its main function is to help the tear fluid stay on the surface of the eye and envelop foreign bodies or bacteria from the outside to activate the defense mechanism. The secretion of mucin from goblet cells is controlled by parasympathetic nerves, and secretion becomes excessive due to irritation to the ocular surface. Under normal circumstances, ocular lipids sometimes appear on the ocular surface, especially in high temperature environments or when you get up, it is normal and common.

As a general treatment method for eyelids, it is recommended to wipe with clean paper towels, gauze, cotton swabs, etc. However, since the removal is performed physically, the ocular surface may be damaged. In addition, in general eye drops and artificial tears that are approved for the manufacture and sale of over-the-counter medicines, it is possible to emphasize "eye blur (long-term eye fat, etc.)" as an effect or effect without blending specific active ingredients. Therefore, artificial tears are thought to treat mild eyelids by the flushing effect brought about by dripping into the eyes. However, because it is a rinsing effect brought by dripping into the eyes, the effect as a treatment for severe eye fat is insufficient, and there is room for improvement.

The causes of dullness include those caused by organic diseases and those caused by psychogenic factors. As organic diseases, there are ophthalmic diseases (external eye diseases such as accommodative eye fatigue, ocular muscle fatigue, glaucoma, dry eye, and optic nerve diseases), and intracranial diseases such as intracranial ulcers. Examples of the treatment method include treating a disease as a cause, but a symptomatic treatment effective for bluntness has not been known so far.

In addition, in recent years, the use of electronic terminals such as personal computers (Video Display Terminal (VDT)) to maintain the state of watching the monitor, complaints of dry eyes (eyes) or dry eye disease increased . The term "dry eye disease" refers to a condition in which the tear fluid is reduced or a substantial abnormality occurs, or the corneal and conjunctival disorders are caused by abnormalities in the quantity or quality of the tear fluid. Examples of subjective symptoms include eye fatigue, congestion, dryness, foreign body sensation, blurring, shame, itching, pain, poor distance adjustment, eyelids, tears, and dullness. Major inconvenience. In view of the above-mentioned circumstances, techniques for alleviating dry eye have been proposed (for example, refer to Patent Documents 1 to 3). There are many aspects of dry eye. Therefore, a technique that can alleviate the symptoms and can be easily used is desired. [Prior Art Literature] [Patent Literature]

Patent Literature 1: Japanese Patent Laid-Open No. 2015-160826 Patent Literature 2: Japanese Patent Laid-Open No. 2012-077080 Patent Literature 3: Japanese Patent Laid-Open No. 2010-120856

[Problems to be Solved by the Invention] An object of the present invention is to provide at least one selected from the group consisting of eye fat production, dullness, eye fatigue, blurred eyes, congestion, shame, and itchy eyes. A symptomatic ophthalmic preparation. [Means for solving problems]

The present inventors conducted diligent research on the above-mentioned problems, and as a result, they found that (A) hydroxypropyl methylcellulose (hereinafter, also referred to as "hypromellose" in this specification) And (B) vitamin E-based ophthalmic agents to solve the above-mentioned problems, and completed the present invention. In addition, it has been found that the desired efficacy is further improved by further containing (C) an ophthalmic agent of vitamin A type. That is, the present inventors and others provide the following [1] to [12]. [1] An agent for preventing lipogenesis, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. [2] A dullness inhibitor, which contains: (A) hydroxypropyl methyl cellulose and (B) vitamin E. [3] An eye fatigue reliever containing: (A) hydroxypropyl methylcellulose and (B) vitamin E. [4] An eye blur reducing agent, which contains: (A) hydroxypropyl methylcellulose and (B) vitamin E. [5] A congestion inhibitor, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. [6] A shame reliever, which contains: (A) hydroxypropyl methylcellulose and (B) vitamin E. [7] An itching suppressant for the eyes, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. [8] The medicament according to any one of the above [1] to [7], further comprising (C) vitamin A. [9] The pharmaceutical agent according to [8], wherein the amount of the (C) vitamin A is 50,000 international units (I.U.) to 500,000 I.U. per 100 mL of the medicine. [10] The agent according to any one of the above [1] to [9], which is at least one of a therapeutic and preventive agent for dry eye. [11] The medicament according to any one of the above [1] to [9], which is at least any one for the treatment and prevention of dry eyes. [12] An ophthalmic drug using the medicament according to any one of [1] to [11]. [Effect of the invention]

According to the present invention, there can be provided an ophthalmic agent that can be used to improve at least one symptom selected from the group consisting of eye fat production, dullness, eye fatigue, blurry eyes, congestion, shame, and itchy eyes, and An ophthalmic agent using the ophthalmic agent.

Hereinafter, the present invention will be described in detail with reference to its preferred embodiments. In addition, in this specification, unless otherwise stated, the concentration (W / V%) of each component has the same meaning as "g / 100 mL".

In the present specification, the "vitamin E" refers to vitamin E itself, as well as tocopherol and tocotrienol, as well as vitamin E salts and vitamin E derivatives.

In the present specification, "vitamin A" refers to vitamin A-containing mixtures such as vitamin A oil and vitamin A derivatives such as vitamin A fatty acid esters, in addition to vitamin A itself.

In the present specification, the "ophthalmic agent" means selected from the group consisting of (A) hydroxypropyl methylcellulose and (B) vitamin E, and is selected from the group consisting of prevention of eye fat, suppression of dullness, relief of eye fatigue, An agent that relieves at least one of the symptoms of the group consisting of blurring eyes, suppressing congestion, reducing shame, and suppressing itching of eyes.

In the present specification, the "ophthalmic drug" refers to a person who specifies an ophthalmic agent in the form of a product such as an eye drop or an eye wash.

[1. Ophthalmic preparations] Ophthalmic preparations are those containing (A) hydroxypropyl methylcellulose and (B) vitamin E. The ophthalmic agent preferably further contains (C) vitamin As.

(A) The component alone has only a slight effect of reducing eye blur (see Comparative Example 2). In addition, the component (B) alone exhibited only a slight effect of reducing eye fatigue (see Comparative Example 3). On the other hand, the combination of the ophthalmic agent containing the component (A) and the component (B), compared with the case of containing the component (A) or (B) alone, not only improves the effectiveness of reducing eye blur and eye fatigue, but also achieves (A) or (B) of the component is not effective at all in relieving symptoms: prevention of eye fat production, suppression of dullness, suppression of congestion, relief of shame, suppression of itchy eyes. The ophthalmic agent can further improve the above-mentioned symptoms by further containing the component (C).

From the viewpoint of the appearance stability of the preparation, the (A) component and the (B) component represented by [(A) component (W / V%)] / [(B) component (W / V%)] The ratio is preferably 0.02 to 200, more preferably 0.03 to 150, and still more preferably 0.04 to 100. In addition, the ratio of the (B) component to the (C) component represented by [(B) component (W / V%)] / [(C) component ((ten thousand units) / 100 mL)] is preferably 0.00005 to 0.5, more preferably 0.000075 to 0.4, and still more preferably 0.0001 to 0.25. Furthermore, the ratio of (A) component to (C) component represented by [(A) component (W / V%)] / [(C) component ((ten thousand units) / 100 mL)] is preferably 0.0001 to 1, more preferably 0.00015 to 0.75, and still more preferably 0.0002 to 0.5.

The ophthalmic agent is excellent in the effectiveness of preventing the formation of eye fat, suppressing dullness, alleviating eye fatigue, alleviating eye blur, suppressing congestion, alleviating shame, and itching of eyes. Therefore, it can be effectively used for at least one of the treatment and prevention of dry eye symptoms and dry eye symptoms.

[2. (A) Hydroxypropyl methylcellulose (also known as hypromellose)] About component (A), it has been known that it was used as a thickener in the formulation design and manufacturing of medical eye drops. It is formulated and used for the purpose of improving the retention of the drug in the conjunctival sac, the continuity of the drug effect, or the intraocular metastasis (refer to the Japan Society of Ophthalmic Agents HP). That is, the component (A) assists the efficacy of other medicinal ingredients. On the other hand, an ophthalmic agent containing the component (A) exerts an effect based on an unknown attribute that suppresses blurring of the eyes, which has not been previously known.

The lower limit of the weight-average molecular weight of hypromellose is preferably 10,000 (g / mol) or more, and more preferably 30,000 (g / mol) or more, in terms of further exerting desired performance. It is preferably 50,000 (g / mol) or more. On the other hand, in terms of further preventing unclearness after dripping into the eyes, the upper limit value is preferably 800,000 (g / mol) or less, more preferably 600,000 (g / mol) or less, and even more preferably Below 400,000 (g / mol). Furthermore, the weight average molecular weight of hypromellose can be measured by a gel permeation chromatography-multi angle laser light scatting (GPC-MALLS) system. More specifically, it can be measured under the following conditions. [Measurement conditions] Column: ShodEx SB-806MHQ (column temperature: 40 ° C) Eluent: 0.1 mol / L (NANO3: 1.0 mL / min) Solvent: 0.1 mol / L (NANO3) Injection volume: 200 μL [Device Liquid delivery pump: ShodEx DS-4 (manufactured by Showa Denko) Light scattering detector (MALLS): DAWN DSP WyAtt TEchonology Corportion Concentration detector: ShodEx R1-71 (manufactured by Showa Denko)

As (A) component, a commercial item can be used. Examples of the commercially available product include "METOLOSE 60SH-4000 (weight average molecular weight approximately 300,000 (g / mol))" or "METOLOSE 60SH" manufactured by Shin-Etsu Chemical Industry Co., Ltd. -50 (weight average molecular weight about 70,000 (g / mol)) "and so on. Moreover, (A) component may be used individually by 1 type, and (A) component which has a different weight average molecular weight may be used combining two or more types by arbitrary ratios.

The lower limit of the concentration of the component (A) is preferably 0.01 W / V% or more, and more preferably 0.05 W / V% or more. By setting it as the range, desired performance can be exhibited. On the other hand, the upper limit value is preferably 1 W / V% or less, more preferably 0.8 W / V% or less, and still more preferably 0.7 W / V% or less. By setting it as this range, it becomes difficult to generate the blur after dripping into an eye.

[3. (B) Vitamin E] It is known that the component (B) can promote blood circulation or antioxidant, and can be used in eye drops for cataract treatment. On the other hand, an ophthalmic agent containing the component (B) exhibits a previously unknown effect based on unknown properties, which suppresses eye fatigue.

(B) A component can be used without a restriction | limiting as long as it is a component which can be used for an ophthalmic preparation. The component (B) is preferably vitamin E such as reproductive phenol and ginseng double bond reproductive phenol, and salts and derivatives thereof. Examples of vitamin E include d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol. The vitamin E salt is not particularly limited as long as it is medically, pharmacologically (pharmaceutically), or physiologically acceptable. Examples include salts with organic bases (for example, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, and methylpyridine), and salts with inorganic bases. Salts (for example: ammonium salts; alkali metal salts such as sodium and potassium; alkaline earth metal salts such as calcium and magnesium; metal salts such as aluminum). Examples of the vitamin E derivative include vitamin E acetate (reproductive acetic acid acetate), vitamin E nicotinate, vitamin E succinate, and vitamin E threonine oleate. Among these, tocopherol acetate (d-α-tocopheryl acetate, dl-α-tocopherol acetate, etc.) is preferred.

As the component (B), for example, a Japanese Pharmacopoeia contained product can be preferably used. Furthermore, the (B) component may be used alone, or two or more different types of the (B) component such as reproductive phenol, ginseng double bond reproductive phenol, salts or derivatives thereof may be used in combination at an arbitrary ratio.

The lower limit value of the concentration of the component (B) is preferably 0.005 W / V% or more, and more preferably 0.01 W / V% or more. With this range, desired performance can be exhibited. On the other hand, the upper limit value is preferably 0.5 W / V% or less, and more preferably 0.2 W / V% or less. Within this range, the component (B) can be dissolved and the appearance stability can be maintained.

[4. (C) Vitamin A] The component (C) is known to play a role in promoting mucin production and healing corneal trauma. Therefore, the component (C) is used as a drug effective for the treatment of dry eye disease, which is effective in repairing the tear mucin layer and treating corneal and conjunctival disorders. On the other hand, in ophthalmic preparations, the component (C) suppresses dullness or promotes the production of mucin, which can cause the formation of eye fat, while preventing the production of eye fat. Power based on unknown attributes.

(C) A component can be used without a restriction | limiting as long as it is a component which can be used for an ophthalmic preparation. Examples of the component (C) include vitamin A groups such as retinol, retinal, retinoic acid, and 3-dehydrogen; and vitamin A oil and the like A mixture of vitamin A; vitamin A derivatives such as vitamin A fatty acid esters. Specific examples of the vitamin A derivative include retinol palmitate, retinol acetate, and the like. As component (C), retinol palmitate, retinol acetate, and retinoid are preferred.

As (C) component, a commercial item can be used. For example, about 1 million I.U. to 1.8 million I.U. are commercially available as retinol palmitate. More specifically, "Retinyl Palmitate (1.7 million IU / g)" manufactured by Roche, Vitamin, Japan; "DSM Nutrition Japan" Retinol palmitate (1.74 million IU / g) "and so on. Furthermore, the component (C) may be used singly, or different types of (C) components such as retinol, retinol, retinoid, retinol palmitate, and retinol acetate may be used arbitrarily. The ratio is used in combination of two or more.

(C) The amount of the component is defined by the international unit (I.U.) determined by a method described in the 16th revised edition of the Japanese Pharmacopoeia Vitamin A Quantitative Method. The lower limit of the amount of the component (C) is preferably 10,000 I.U. or more, more preferably 50,000 I.U. or more, with respect to the capacity of the ophthalmic agent 100 mL. By setting it as the range, desired performance can be further improved. On the other hand, the upper limit of the amount of the component (C) is preferably 1 million I.U. or less, more preferably 500,000 I.U. or less, with respect to the volume of the ophthalmic agent 100 mL. By setting it as the said range, stability of (C) component can be maintained.

[5. Other components] In the ophthalmic agent, other components can be blended in an appropriate amount within a range that does not impair the effects of the present invention. Examples of the other components include surfactants, preservatives, sugars, buffers, pH adjusters, isotonic agents, stabilizers, polyols, thickeners, cooling agents, and drugs. These components can be formulated alone or in a suitable combination.

<Surfactant> Examples of the surfactant include polyoxyethylene sorbitan fats such as polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, and polyoxyethylene sorbitan oleate. Nonionic surfactants such as acid esters; glycine type amphoteric surfactants such as alkyldiaminoethylglycine. In terms of improvement of the symptoms of the present application, polyoxyethylene polyoxypropylene glycol is preferred. The concentration of the surfactant is preferably 0.0001 W / V% to 15 W / V%, and more preferably 0.005 W / V% to 10 W / V%. However, in terms of eye irritation, the concentration of the surfactant is preferably thinner, more preferably 5 W / V% or less.

<Preservatives> Examples of the preservatives include sorbic acid or a salt thereof such as benzalconium chloride, benzethonium chloride, and potassium sorbate, and parabens (parabens) Methyl benzoate, ethyl paraben, propyl paraben, etc.), chlorhexidine gluconate, thimerosal, phenylethyl alcohol, alkane hydrochloride Diaminoethylglycine, Polidronium chloride, Polyhexanide chloride. The concentration of the preservative is preferably 0.00001 W / V% to 5 W / V%, more preferably 0.0001 W / V% to 3 W / V%, and still more preferably 0.001 W / V% to 2 W / V%.

<Sugars> Examples of the saccharides include glucose such as glucose, cyclodextrin, xylitol, sorbitol, and mannitol. Furthermore, these may be any of d-body, l-body, or dl-body. The sugar concentration is preferably from 0.001 W / V% to 5.0 W / V%.

<Buffering agent> Examples of the buffering agent include citric acid, sodium citrate, boric acid, borax, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, glacial acetic acid, trometamol, and sodium bicarbonate. The concentration of the buffering agent is preferably from 0.001 W / V% to 5.0 W / V%.

<PH adjuster> As a pH adjuster, it is preferable to use an inorganic acid or an inorganic alkali agent. Examples of the inorganic acid include (dilute) hydrochloric acid. Examples of the inorganic alkali agent include sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium bicarbonate. Among these, hydrochloric acid and sodium hydroxide are preferred. The concentration of the pH adjuster is preferably 0.00001 W / V% to 10 W / V%, more preferably 0.0001 W / V% to 5 W / V%, and still more preferably 0.001 W / V% to 3 W / V%. .

<Isotonicity agent> Examples of the isotonicity agent include sodium chloride and potassium chloride. The concentration of the isotonicity agent is preferably 0.001 W / V% to 5 W / V%, more preferably 0.01 W / V% to 3 W / V%, and still more preferably 0.1 W / V% to 2 W / V. %.

<Stabilizer> Examples of the stabilizer include sodium edetate, cyclodextrin, sulfite, and dibutylhydroxytoluene. The concentration of the stabilizer is preferably from 0.001 W / V% to 5.0 W / V%.

<Polyol> Examples of the polyol include glycerol, propylene glycol, butylene glycol, and polyethylene glycol. In the case of blending a polyol, the concentration of the polyol is preferably from 0.001 W / V% to 5.0 W / V%, and more preferably from 0.001 W / V% to 1 in terms of affecting the stability of the formulation. W / V%.

<Viscosity> Examples of the viscosity include polyvinylpyrrolidone, hydroxyethyl cellulose, methyl cellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, polyacrylic acid, and carboxyvinyl polymer. In the case of blending a viscosity agent, the concentration of the viscosity agent is preferably 0.001 W / V% to 5.0 W / V%.

<Cooling agent> Examples of the cooling agent include menthol, camphor, borneol, geraniol, eucalyptol, and linalool. In the case of blending a cooling agent, the concentration of the cooling agent is preferably 0.0001 W / V% to 0.1 W / V%.

<Drugs> Examples of drugs (pharmaceutically effective ingredients) include decongestant components (eg, adrenaline, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphthozoline hydrochloride, Naphthozoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, etc.), anti-inflammatory astringent agents (eg, neostigmine methyl sulfate (neostigmine) methyl sulfate), ε-aminocaproic acid, allantoin, berberine chloride hydrate, berberine sulfate hydrate, sodium sulfonate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate , Lysozyme hydrochloride, etc.), antihistamines (for example, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), water-soluble vitamins (flavin adenine dinucleotide sodium, Cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, etc., amino acids (eg, potassium L-aspartate, magnesium L-aspartate, L-aspartate) Potassium, magnesium (equivalent mixture), amino ethyl sulfonic acid, etc.), sulfonamides, etc. In the case of formulating drugs, regarding the concentration of the drug, an effective adaptive amount of each drug can be selected. In terms of irritation to the eyes and stability of the preparation, it is preferably 0.001 W / V% to 5.0 W / V%.

[6. Preparation method] There is no particular limitation on the preparation method of the ophthalmic agent. For example, it can be obtained by dissolving vitamin A and vitamin E, which are hardly soluble in water, with polyoxyethylene polyoxypropylene glycol in sterilized and purified water, and then adding hypromellose and each compounding component. The pH was then adjusted. Thereafter, it can be aseptically filled in an appropriate container, for example, a container made of polyethylene terephthalate.

The pH (20 ° C) of the ophthalmic agent is preferably 4.0 to 9.0, more preferably 5.0 to 8.0, and even more preferably 6.0 to 8.0. The pH is a value measured at 20 ° C using a pH osmometer ("HOSM-1"; manufactured by Toya DKK).

The viscosity of the ophthalmic agent is preferably 2.5 mPa ･ s to 120 mPa ･ s, and more preferably 6 mPa ･ s to 60 mPa ･ s. The viscosity measurement can be performed at 20 ° C using an E-type viscometer (for example, VISCONIC ELD-R, manufactured by Tokyo Keiki Co., Ltd.).

The packaging of the container is preferably an oxygen-adsorbed pillow-type packaging, rather than a pillow-type packaging such as polyethylene, polyethylene terephthalate, and the like. This can further improve the stability of the (C) component. In addition, the "oxygen pillow type packaging" refers to a pillow using an oxygen absorber kneading film, which can actively remove oxygen remaining in the pillow and oxygen invading from the outside.

[7. Use preparations] The ophthalmic agent is selected from the group consisting of an eye fat production inhibitor, a dullness inhibitor, an eye fatigue reducer, an eye blur reducer, a congestion inhibitor, a shame reliever, and an eye itching inhibitor. At least one potent use formulation in the group.

<Eyeslipids> Eyelids are caused by conjunctival inflammation and excessive secretion of ocular surface mucus (mucin). The exudate, which is the source of ocular fat, exudates from the dilated conjunctival blood vessels and reaches the ocular surface through the conjunctival epithelium. Eyelids are made by mixing mucus (mucin) or epithelial cells. Mucin is secreted by conjunctival goblet cells, and its main function is to help the tear fluid stay on the surface of the eye, and it is a defense mechanism that activates foreign bodies or bacteria from the outside. The secretion of mucin from goblet cells is controlled by parasympathetic nerves, and secretion becomes excessive due to irritation to the ocular surface. Under normal circumstances, eyelids sometimes appear on the ocular surface. Eye fat is secreted especially in high temperature environments or when getting up. This is normal and common.

As a general treatment method for eyelids, it is recommended to wipe with clean paper towels, gauze, cotton swabs, etc. However, since the removal is performed physically, the ocular surface may be damaged. In addition, in general eye drops and artificial tears that are approved for the manufacture and sale of over-the-counter medicines, it is possible to emphasize "eye blur (long-term eye fat, etc.)" as an effect or effect without blending specific active ingredients. Therefore, with the rinsing effect brought by dripping into the eyes, mild eye fat is treated. However, it is not effective as a treatment for severe eye fat such as dry eye symptoms or dry eye symptoms.

Hypromellose and vitamin E are blended in the anti-lipid production preventing agent of the present invention, and therefore, the "eye fat" is suppressed, and the effect can be improved by blending vitamin A. In particular, it has excellent efficacy when it produces dry eyes or "severe prevention of eye fat production" in dry eye disease.

<Dullness> Dullness refers to a condition in which the eyes feel heavy. The causes of dullness include those caused by organic diseases and those caused by psychogenic factors. Organic diseases include ophthalmic diseases (external eye diseases such as accommodative eye fatigue, ocular muscle fatigue, glaucoma, dry eye disease, and optic nerve disease) and intracranial diseases such as intracranial ulcers. Examples of the treatment method include treating a disease as a cause, but a symptomatic treatment effective for bluntness has not been known so far.

Hypromellose and vitamin E are blended in the dullness suppressing agent of the present invention, so that the "bluntness" is suppressed, and the effect can be improved by blending vitamin A. In particular, it exhibits excellent performance when it produces dryness symptoms or "inhibition of dullness" in dry eye disease.

＜ Eye fatigue> Causes of eye fatigue include: eye disorders such as myopia, astigmatism, presbyopia, dry eye disease, glaucoma; physical disorders such as dental caries or periodontal disease, diabetes; living environment using a personal computer or smartphone; Many factors, such as mental stress, can cause symptoms such as eye fatigue. Examples of the previous treatment method include a method of adjusting glasses, instilling vitamin B12 into the eyes, adjusting an activator into the eyes, or promoting blood circulation by repeatedly applying hot / cold compresses. However, there is a problem that the previous dripping to the eyes is insufficient, and there is a problem that is inconvenient for a method of repeatedly performing hot / cold compressing.

Hypromellose and vitamin E are blended in the eye fatigue relieving agent of the present invention. Therefore, "eye fatigue" is relieved, and the effect can be improved by blending vitamin A. In particular, it has excellent performance when it produces dry eyes or "relief of eye fatigue" in dry eye disease.

＜ Fuzzy eyes ＞ The causes of blurred eyes include those caused by organic diseases and those caused by psychogenic factors. Examples of the organic diseases include tear fluid abnormalities, conjunctivitis, keratitis, cataracts, and eye fatigue. Examples of the treatment method include treating a disease that is a cause, but a symptomatic treatment effective for blurring eyes has not been known so far.

Hypromellose and vitamin E are blended in the eye blur reducing agent of the present invention, so that "eye blur" is relieved, and by blending vitamin A, the effect can be improved. In particular, it can exert excellent performance in the case of dry eyes or "eye blur reduction" in dry eye disease.

<Congestion> The cause of congestion ranges from infectious congestion to allergic congestion and traumatic congestion. Examples of the treatment method include administration of an antiallergic agent, eye washing, and cooling of the peripheral part of the eye. However, other than these, no symptomatic treatment effective for congestion has been known so far.

Hypromellose and vitamin E are blended in the congestion inhibitor of the present invention, so that "hyperemia" is suppressed, and the effect can be improved by blending vitamin A. In particular, it exhibits excellent efficacy in the "suppression of hyperemia" when dry eye symptoms occur or in dry eye disease.

<Shame sense> The so-called shame sense refers to a situation in which light is dazzling. One of the causes of shame feeling is abnormality of the cornea, which is a symptom that easily occurs when the cornea is damaged due to dry eye disease or the like. Therefore, eye drops are effective for alleviating symptoms before injury, but for alleviating symptoms after injury, it is necessary to use eye drops in consideration of wounds.

Hypromellose and vitamin E are blended in the shame-relieving agent of the present invention, so the "shame feeling" is relieved, and the effect can be improved by blending vitamin A. In particular, it has excellent performance when it produces dry eyes or "relaxation of shame" in dry eye disease.

<Itchy eyes> The main cause of itchy eyes is allergic conjunctivitis. In dry eye disease, tears are reduced, so the defense mechanism formed by ocular surface mucin is not sufficient, so itchy eyes become a prone symptom. Therefore, in the case of treatment with eye drops, it is desirable to add a component that relieves allergic symptoms, but as described above, in the case of damage to the cornea due to dry eye disease, it may not be desirable to use this ingredient.

Hypromellose and vitamin E are blended in the eye itching inhibitor of the present invention, so that "itching of the eyes" is suppressed, and the effect can be improved by blending vitamin A. In particular, it exhibits excellent performance when it produces dry eyes or "inhibition of eye itch" in dry eye disease.

[Applicable diseases] Ophthalmic agents exhibit excellent improvement effects on the symptoms of eye fat formation, dullness, eye fatigue, blurry eyes, congestion, shame, and itchy eyes. Therefore, they are particularly suitable for dry eyes At least one of treatment and prevention of symptoms or dry eye disease.

[9. Ophthalmic Medicine] The ophthalmic medicine of the present invention uses the above-mentioned ophthalmic medicine. Examples of the ophthalmic agent of the present invention include eye drops, eye wash agents, injections, patches, gels, and inserts. Among them, eye drops are preferred. Furthermore, these can be prepared using common techniques commonly used in the art. Furthermore, in addition to the above, the ophthalmic drug of the present invention can also be made into a drug delivery system (DDS) preparation such as an intraocular implant preparation or a microsphere.

Eye drops and eye wash agents can be selected from sodium chloride, potassium chloride, concentrated glycerin, and other tonicity agents; buffering agents such as sodium phosphate, sodium acetate, and ε-aminohexanoic acid; polyoxyethylene sorbitan Surfactants such as monooleate, stearate 40, polyoxyethylene hydrogenated castor oil; stabilizers such as sodium citrate, sodium edetate; benzyl ammonium chloride, parabens, etc. Preservatives are selected for use. The pH may be within a range allowable for an ophthalmic preparation, and is usually preferably within a range of 4 to 8.

Injectables such as tonicizers such as sodium chloride; buffering agents such as sodium phosphate; surfactants such as polyoxyethylene sorbitan monooleate; optional thickeners such as methyl cellulose preparation.

The insert can be prepared by pulverizing and mixing a biodegradable polymer such as hydroxypropyl cellulose, carboxyvinyl polymer, polyacrylic acid and an ophthalmic agent, and compressing the powder. Furthermore, if necessary, an excipient, a binding agent, a stabilizer, a pH adjuster, and the like can be used.

Preparations for intraocular implants can be prepared using, for example, biodegradable polymers such as polylactic acid, polyglycolic acid, lactic acid / glycolic acid copolymer, and hydroxypropyl cellulose.

The usage of the ophthalmic drug of the present invention can be appropriately changed according to the dosage form, the severity of the symptoms to be given to the patient, age, weight, and the like. For example, when eye drops are selected as the dosage form, 10 μL to 50 μL at a time may be used once to 10 times a day, preferably 2 to 8 times a day, and more preferably 4 times a day to The eye was administered topically 6 times.

The wearers of soft contact lenses and hard contact lenses are in a state where the surface of the eye is easy to dry, the eyes are blurred due to wearing, and the state is more congested than the naked eye. The ophthalmic drug of the present invention is preferably for wearers of soft contact lenses, silicon hydrogel contact lenses, hard contact lenses, oxygen-permeable hard contact lenses, and particularly preferably soft contact lenses that strongly sense dryness, and silicone hydrogel For contact lens wearers. In addition, wearers of soft contact lenses and hard contact lenses are in a state where the cornea is easily damaged, and are easily affected by preservatives. In this respect, it is also preferable that the ophthalmic drug of the present invention does not contain a preservative and is not formulated with a preservative. The wearers of soft contact lenses and hard contact lenses may damage the eyes when wearing contact lenses, or contact lenses may induce bacterial or viral conjunctivitis, which may easily cause eye fat. In addition, wearing contact lenses reduces water on the surface of the eyes, making it easy to feel dry eyes and the onset or dullness of dry eye disease. Therefore, it is preferable that the ophthalmic drug of the present invention is suitable for wearers of soft contact lenses or hard contact lenses. [Example]

Hereinafter, the present invention will be described in more detail through examples. The following examples are intended to better illustrate the present invention, but not to limit the present invention.

[Viscosity (mPa ･ s)] For the ophthalmic preparations prepared in the examples and comparative examples, an E-type viscometer ("VISCONIC ELD-R", manufactured by Tokyo Keiki Co., Ltd.) was used at 20 ° C. The viscosity was measured.

[Evaluation of Symptoms] Among those who have dry eyes and meet the diagnostic criteria for dry eye disease (new ophthalmology 24 (2): 181-184, 2007), they have "eye fat", "bluntness", and "eye fatigue" (Strained eyes), 7 eyes with the symptoms of "blurred eyes", "hyperemia", "shame", and "itchy eyes" were tested. The pre-observation period is set to two weeks. During the pre-observation period, the eye drops are instilled in the pre-observation period (artificial tears "My Tear (MY TEAR) eye drops (Qianju) Pharmaceutical manufacturing) "). About the five group members who did not improve their subjective symptoms during the pre-observation period, the test drug was dripped into the eyes one drop at a time (about 50 μL) six times a day, and the effect of improving the subjective symptoms was investigated. The subjective symptoms (7 items) were evaluated at the beginning of the test drug administration and four weeks after the test drug administration.

The scoring method for the team members' scores is described in Table 1 below.

[Table 1]

A value obtained by subtracting a score value of a score at the start of administration of the test drug from a score value of the respective symptoms at the time of administration of the test drug was set as the amount of change in the score of the target group member. The amount of change was divided by 5 members and averaged, and the subjective symptoms were evaluated on the basis of the following criteria. Excellent: Four weeks after the test drug was given, the change in the score of the subjective symptoms was improved by more than 0.5 points compared with the time when the test drug was started. Good: Four weeks after the test drug was given, the change in the score of the subjective symptoms was higher than the start. When the test drug is improved by 0.3 points or more and less than 0.5 points, the change in the score of the subjective symptoms is improved by more than 0 points to less than 0.3 points when the test drug is administered. Improve effect

(Comparative Example 1) 100 g of polyoxyethylene (200) polyoxypropylene (70) diol and 0.9 g of sodium chloride were dissolved in purified water to prepare an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 2.

(Comparative Example 2) 0.15 g of hypromellose ("METOLOSE 60SH-4000" manufactured by Shin-Etsu Chemical Co., Ltd.) and 1.0 g of polyoxyethylene (200) polyoxypropylene (70) glycol And 0.9 g of sodium chloride was dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 2.

(Comparative Example 3) 0.05 g of d-α-reproductive acetic acid ("RIKEN acetate α" manufactured by Riken Vitamin Co.) and 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol were dissolved in a purified product In water, 0.9 g of sodium chloride was dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 2.

(Example 1) 0.05 g of d-α-tocopherol acetate (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") was dissolved in 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol and refined In water, 0.15 g of hypromellose ("METOLOSE 60SH-4000" manufactured by Shin-Etsu Chemical Industry Co., Ltd .; weight average molecular weight about 300,000) and 0.9 g of sodium chloride were dissolved in purified water to prepare Ophthalmic agent (test drug) 100 mL. The viscosity of the prepared ophthalmic agent was 7 mPa 为 s at 20 ° C, and the pH was 7.1 at 20 ° C. The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are described in Tables 2 and 4.

(Example 2) 0.05 g of d-α-tocopherol acetate (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (RocheRoVitamin ･ Japan) Manufactured by the company, “Retinyl palmitate”) 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The viscosity of the prepared ophthalmic agent was 7 mPa 为 s at 20 ° C, and the pH was 7.1 at 20 ° C. The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are described in Tables 2 to 5.

[Table 2]

From the results of Comparative 1, it can be seen that the ophthalmic agent containing no active ingredient does not produce the desired efficacy at all. In addition, based on the results of Comparative Examples 2 and 3, with regard to ophthalmic agents containing the component (A) or component (B) alone, only the effect of reducing eye fatigue or reducing eye blur was slightly observed, and no other was observed. Amelioration of subjective symptoms. On the other hand, according to the results of Example 1, the ophthalmic agent of the present invention containing the component (A) and the component (B) has an improved effect of reducing eye fatigue or blurring the eyes, as compared with the case where it is contained alone. It exhibits the desired effects of suppressing dullness, preventing eye fat production, suppressing congestion, alleviating shame, and suppressing itching of the eyes, without any improvement in subjective symptoms being observed. It is particularly excellent in terms of eye fatigue (eye fatigue). In addition, according to the results of Example 2, when the component (C) is further contained, while maintaining the effect of alleviating eye fatigue, the eyes are relieved of blurring, bluntness is suppressed, eye fat is prevented, hyperemia is suppressed, and shame is relieved. , The effect of suppressing itching of the eyes is further excellent. From these results, it can be seen that an ophthalmic agent containing the component (A) and the component (B) can be used as an eye blur reducer, a dullness inhibitor, an eye fat production preventive agent, a congestion inhibitor, a shame reliever, A preparation for the use of an eye itch inhibitor.

(Example 3) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (Roche ･ Vitamin ･ Japan) Manufactured by the company, “Retinyl palmitate”) 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-50"; a weight-average molecular weight of about 70,000) and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 3.

[table 3]

Based on the results of Examples 2 and 3, the ophthalmic agent using the component (A) having a large weight average molecular weight is one having excellent efficacy in preventing the production of eye fat, suppressing dullness, suppressing blurring of the eyes, and suppressing itching of the eyes.

(Example 4) 0.05 g of d-α-tocopherol acetate (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 30,000 IU of retinol palmitate (Roche ･ Vitamin ･ Japan) Manufactured by the company, “Retinyl palmitate”) 1.0 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 4.

(Example 5) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 150,000 IU of retinol palmitate (Roche ･ Vitamin ･ Japan) Manufactured by the company, "Retinyl palmitate") 3.0 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co. "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 4.

(Example 6) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 300,000 IU of retinol palmitate (Roche, Vitamin, Japan) Manufactured by the company, "Retinyl palmitate") 5.0 g of polyoxyethylene (200) polyoxypropylene (70) glycol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co. "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 4.

(Example 7) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., “RIKEN acetate α”) and retinol palmitate 500,000 IU (Roche ･ Vitamin ita Japan) Manufactured by the company, "Retinyl palmitate") 5.0 g of polyoxyethylene (200) polyoxypropylene (70) glycol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 4.

[Table 4]

According to the results of Example 1 and Example 4, if the component (C) of 30,000 I.U. is further contained, the effect of suppressing hyperemia and alleviating eye itch is improved. In addition, according to the results of Example 2, Example 5 to Example 7, if the amount of the (C) component is 50,000 IU or more, the production of eye fat is prevented, the dullness is suppressed, the eye fatigue (eye fatigue) is relieved, and the eyes are relieved. It is excellent in blurring, suppressing congestion, alleviating shame, and suppressing itchy eyes. From these results, it can be seen that ophthalmic agents containing the component (C) in addition to the components (A) and (B) are used as an eye blur reducer, a dullness suppressor, an agent for preventing eye fat production, and a hyperemia inhibitor. In the case of using an agent, a stigma mitigating agent, or an eye itching inhibitor, the amount of the component (C) is preferably 50,000 IU or more.

(Example 8) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (RocheitaVitamin ･ Japan) Manufactured by the company, "Retinyl palmitate" was dissolved in purified water with 0.2 g of polyoxyethylene (200) polyoxypropylene (70) diol, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Industry Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 5.

(Example 9) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (Roche ･ Vitamin ･ Japan) Manufactured by the company, "Retinyl palmitate") 0.3 g of polyoxyethylene (200) polyoxypropylene (70) diol was dissolved in purified water, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 5.

(Example 10) 0.05 g of d-α-reproductive acetic acid (manufactured by RIKEN Vitamin Co., Ltd., "RIKEN acetate α") and 50,000 IU of retinol palmitate (Roche, Vitamin, Japan) Manufactured by the company, "Retinyl palmitate" was dissolved in purified water with 0.4 g of polyoxyethylene (200) polyoxypropylene (70) diol, and then 0.15 g of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) "METOLOSE 60SH-4000") and 0.9 g of sodium chloride were dissolved in purified water to prepare 100 mL of an ophthalmic agent (test drug). The prepared ophthalmic agent was used to evaluate subjective symptoms. The results are shown in Table 5.

[table 5]

When the amount of polyoxyethylene (200) polyoxypropylene (70) diol is reduced to 0.2 W / V%, the effect of reducing eye blur is slightly reduced (see Example 8). On the other hand, if the amount of polyoxyethylene (200) and polyoxypropylene (70) diol is 0.3 W / V% or more, it prevents the formation of eye fat, suppresses dullness, relieves eye fatigue (eye fatigue), and reduces eye blur. , The effect of suppressing congestion, alleviating shame, and suppressing itching of the eyes are excellent (refer to Example 2, Example 9 to Example 10).

The following describes prescription examples when an ophthalmic agent is applied to the ophthalmic agent of the present invention. 1. Eye drops [Table 6]

The raw materials used when preparing the eye drops of Formulation Examples 1 to 5 in Table 6 are shown below. ･ Polyoxyethylene (200) polyoxypropylene (70) diol: "UNILUB 70DP-950B", Yasushi Kiyoshi, manufactured by Nippon Oil Company, or "Lutrol F127", Yasushi Shiki , Basf (BASF) company made 纤维素 hydroxypropyl methylcellulose (hypromellose): "METOLOSE 60SH-4000", manufactured by the Japanese Pharmacopoeia, Shin-Etsu Chemical Industry Co., Ltd., weight average molecular weight 300,000 (G / mol) ･ Monooleic acid polyoxyethylene (20) Sorbitan (Polysorbate 80): "Reoodol TW-0120V", Japanese Pharmacopoeia, Kao Corporation ･ Polyoxygen Ethylene hydrogenated castor oil 60: "HCO-60 (for medical use)", medicinal supplement, manufactured by Nikko Chemical Co., Ltd.

[TABLE 7]

The raw materials used when preparing the eye drops of Formulation Examples 6 to 10 in Table 7 are shown below. ･ Polyoxyethylene (200) polyoxypropylene (70) diol: "UNILUB 70DP-950B", Yasushi Kiyoshi, manufactured by Nippon Oil Company, or "Lutrol F127", Yasushi Shiki , Basf (BASF) company made 纤维素 hydroxypropyl methylcellulose (hypromellose): "METOLOSE 60SH-4000", manufactured by the Japanese Pharmacopoeia, Shin-Etsu Chemical Industry Co., Ltd., weight average molecular weight 300,000 (G / mol) ･ Monooleic acid polyoxyethylene (20) Sorbitan (Polysorbate 80): "Reoodol TW-0120V", Japanese Pharmacopoeia, Kao Corporation ･ Polyoxygen Ethylene hydrogenated castor oil 60: "HCO-60 (for medical use)", medicinal supplement, manufactured by Nikko Chemical Co., Ltd.

2. Eyewash [Table 8]

The raw materials used in the preparation of the eye wash preparations of Formulation Examples 11 to 13 in Table 8 are shown below. ･ Polyoxyethylene (200) polyoxypropylene (70) diol: "UNILUB 70DP-950B", Yasushi Kiyoshi, manufactured by Nippon Oil Company, or "Lutrol F127", Yasushi Shiki , Basf (BASF) company made 纤维素 hydroxypropyl methylcellulose (hypromellose): "METOLOSE 60SH-4000", manufactured by the Japanese Pharmacopoeia, Shin-Etsu Chemical Industry Co., Ltd., weight average molecular weight 300,000 (G / mol) ･ Monooleic acid polyoxyethylene (20) Sorbitan (Polysorbate 80): "Reoodol TW-0120V", Japanese Pharmacopoeia, Kao Corporation ･ Polyoxygen Ethylene hydrogenated castor oil 60: "HCO-60 (for medical use)", medicinal supplement, manufactured by Nikko Chemical Co., Ltd.

no

no

Claims (18)

An eye fat production preventing agent comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. A dullness inhibitor, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. An eye fatigue relieving agent comprising: (A) hydroxypropylmethyl cellulose and (B) vitamin E. An eye blur reducing agent containing: (A) hydroxypropyl methyl cellulose and (B) vitamin E. A congestion inhibitor comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. A shame relief agent containing: (A) hydroxypropyl methyl cellulose and (B) vitamin E. An eye itch inhibitor, comprising: (A) hydroxypropyl methylcellulose and (B) vitamin E. The medicament according to any one of claims 1 to 7 of the scope of patent application, further comprising (C) vitamin A. The medicament according to item 8 of the scope of patent application, wherein the amount of (C) vitamin A is 50,000 to 500,000 international units per 100 mL of the medicament. The medicament according to any one of claims 1 to 7 of the scope of patent application, which is at least one of a treatment and a prevention for dry eye. The medicament according to item 8 of the scope of patent application, which is at least one of a treatment and a prevention for dry eye. The medicament according to item 9 of the scope of patent application, which is at least one of a treatment and a prevention for dry eye. The medicament according to any one of claims 1 to 7 of the scope of patent application, which is at least one of a treatment and a prevention for dry eyes. The medicament according to item 8 of the scope of patent application, which is at least one of treatment and prevention for dry eyes. The medicament according to item 9 of the scope of patent application, which is at least one of a treatment and a prevention for dry eyes. An ophthalmic drug using the medicament according to any one of claims 1 to 7 of the scope of patent application. An ophthalmic medicine using the medicine described in item 8 of the scope of patent application. An ophthalmic medicine using the medicine described in item 9 of the scope of patent application.