KR20150062139A - Ophthalmic composition - Google Patents

Abstract

The present invention provides an ophthalmic composition which provides a xerophthalmia treatment effect of vitamin A and causes less blurriness of vision after application on eyes. The ophthalmic composition contains (A) vitamin A, (B) 0.05-1.5 W/V% of a non-ionic surfactant, (C) 0.1-0.8W/V% of hydroxypropylmethylcellulose, and (D) polyvinyl pyrrolidone.

Description

[0001] OPHTHALMIC COMPOSITION [0002]

The present invention relates to an ophthalmic composition containing vitamin A.

Vitamin A is a highly effective ingredient in ocular drying. A method of improving the efficacy by increasing the retentivity of vitamin A by mixing a water-soluble polymer compound has been proposed so far, but the effect thereof is not sufficient. Further, a technique for improving the effect of dry eye treatment by adding polyoxyethylene polyoxypropylene glycol to a composition containing 50,000 units / 100mL or more of vitamin A has been proposed (Patent Document 1: JP-A No. 2011-06348) . In addition, when vitamin A is low in concentration, it is required to exert the effect of ocular dry treatment of vitamin A in use of other surfactant, and to improve the feeling of use and the like.

Japanese Patent Application Laid-Open No. 2011-06348

By adding polyoxyethylene polyoxypropylene glycol, the effect of treating ocular dryness is improved. However, when the amount is large, there is a symptom of clouding after the eye drops. In addition, when the water-soluble polymer compound is blended, the effect of treating ocular dryness is improved, but there is also a symptom of blurring after the eye drops. In particular, it is important to alleviate blurring after eye drops because patients with ocular dry tend to feel blurred in the eyes because there is little leakage liquid. It is an object of the present invention to provide an ophthalmic composition which exhibits the ocular dry treatment effect of vitamin A and alleviates blurring after an eye drop.

(B) a nonionic surfactant in an amount of 0.05 to 1.5 g / 100 mL, (C) a hydroxypropyl (meth) acrylate, and Methyl cellulose and (D) a polyvinylpyrrolidone, and (C) the amount of hydroxypropylmethylcellulose blended in an amount of 0.1 to 0.8 g / 100 mL, The present invention has been accomplished on the basis of the knowledge that it has a remarkable effect as an ocular-drying treatment agent by alleviating blur after an eye drop.

Accordingly, the present invention provides the following ophthalmic compositions.

[One]. (A) Vitamin A,

(B) 0.05 to 1.5 W / V% of a nonionic surfactant,

(C) 0.1 to 0.8 W / V% of hydroxypropyl methylcellulose, and

(D) a polyvinylpyrrolidone.

[2]. The composition for ophthalmologic use according to [1], wherein the weight ratio of (C): (D) is from 1.5: 1 to 30: 1.

[3]. The ophthalmic composition according to [1] or [2], wherein the content of the component (D) is 0.01 to 0.5 g / 100 mL.

[4]. The ophthalmic composition according to any one of [1] to [3], wherein the component (A) is at least one member selected from the group consisting of retinol palmitate, retinol acetate and retinoic acid.

[5]. The ophthalmic composition according to any one of [1] to [4], wherein the component (B) is at least one selected from the group consisting of polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil and polyoxyethylene sorbitan fatty acid ester.

[6]. The ophthalmic composition according to any one of [1] to [5], wherein the weight average molecular weight of the hydroxypropyl methylcellulose (C) is 5-60,000 (g / mol).

[7]. The ophthalmic composition according to any one of [1] to [6], wherein the weight average molecular weight of the polyvinyl pyrrolidone (D) is 3 to 1.5 million (g / mol).

[8]. The ophthalmic composition according to any one of [1] to [7], which is a treatment for drying an eye.

(Effects of the Invention)

According to the present invention, it is possible to provide an ophthalmic composition which exhibits the ocular dry therapeutic effect of vitamin A and alleviates blurring after eye drop, thereby having a remarkable effect as an ocular dry therapeutic agent.

(A) Vitamin A

As the vitamin A, in addition to the vitamin A itself, a vitamin A-containing mixture such as vitamin A oil and a vitamin A derivative such as a vitamin A fatty acid ester can be used, and they can be used singly or in combination of two or more. Specific examples thereof include retinol palmitate, retinol acetic acid ester, retinoic acid, retinol, retinoic acid, and retinoid. Among them, retinol palmitate, retinol acetate and retinoic acid are preferred. Retinol palmitate is generally commercially available in the range of 1 million to 1.8 million international units (hereinafter abbreviated as units or IU), specifically retinol palmitate ester (1.7 million IU / g) manufactured by Roche Vitamin Japan . The amount of vitamin A is preferably 10,000 to 500,000 units / 100 mL, more preferably 30,000 to 500,000 units / 100 mL, and particularly preferably 50,000 to 300,000 units / 100 mL. It is preferably 10,000 units / 100 mL or more in view of the effect of ocular drying treatment, and 500,000 units / 100 mL or less in terms of vitamin A stability is preferable.

(B) a nonionic surfactant

Examples of the nonionic surfactant include polyoxyethylene polyoxypropylene glycol, polyoxyethylene hardened castor oil, and polyoxyethylene sorbitan fatty acid ester, which can be used singly or in combination of two or more. Among them, polyoxyethylene polyoxypropylene glycol and polyoxyethylene hydrogenated castor oil are preferable from the viewpoint of ocular dry treatment effect.

The polyoxyethylene polyoxypropylene glycol is not particularly limited, and those listed in the standard for pharmaceutical additives (approx.) Can be used. The average degree of polymerization of ethylene oxide is preferably 4 to 200, more preferably 20 to 200, and the average degree of polymerization of propylene oxide is preferably 5 to 100, more preferably 20 to 70, . Specifically, it is preferable to use polyoxyethylene (120) polyoxypropylene (40) glycol (Pluronic) such as polyoxyethylene (200) polyoxypropylene (70) glycol: Lutrol F127 (BASF), UNILUB 70DP-950B (NOF CORPORATION) F-87), polyoxyethylene (160) polyoxypropylene (30) glycol (Pluronic F-68, nickname poloxamer 188), Plonon # 188P (NOF CORPORATION), polyoxyethylene (42) polyoxypropylene (67) (20) polyoxypropylene (20) glycols, such as Pluronic P123 (alias poloxamer 403), polyoxyethylene (54) polyoxypropylene (39) Pluronic P85: Plonon # 235P (NOF CORPORATION) (Pluronic L-44), Tetronic and the like. Among them, polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol and polyoxyethylene (54) polyoxypropylene (39) glycol are preferable.

Examples of the polyoxyethylene hardened castor oil include polyoxyethylene hardened castor oil 5, polyoxyethylene hardened castor oil 10, polyoxyethylene hardened castor oil 20, polyoxyethylene hardened castor oil 40, polyoxyethylene hardened castor oil 50, polyoxyethylene Hardened castor oil 60, polyoxyethylene hardened castor oil 100, and the like. Among them, polyoxyethylene hardened castor oil 60 is preferable.

Examples of polyoxyethylene sorbitan fatty acid esters include monolauric polyoxyethylene (20) sorbitan (polysorbate 20), monooleic acid polyoxyethylene (20) sorbitan (polysorbate 80), polyoxyethylene sorbitan mono Stearate (polysorbate 60), and polyoxyethylene sorbitan tristearate (polysorbate 65). These may be used singly or in combination of two or more. Of these, polysorbate 80 is preferred.

The content of the nonionic surfactant in the ophthalmic composition is 0.05 to 1.5 W / V% (g / 100 mL), preferably 0.1 to 1.2 W / V%. If the content is less than 0.05 W / V%, the effects of emulsification / solubilization and ocular dry treatment become insufficient. On the other hand, if it exceeds 1.5 W / V%, blur after the application of the ink is observed.

(C) Hydroxypropylmethylcellulose

The weight average molecular weight of hydroxypropyl methylcellulose is preferably 50,000 (g / mol) or more from the viewpoint of exerting an effect of ocular drying treatment, and it is preferably 600,000 (g / mol) or less from the viewpoint of preventing blur desirable. More preferably from 10 to 500,000 (g / mol), and still more preferably from 20 to 400,000 (g / mol). Further, the weight average molecular weight is measured by a GPC-MALLS system.

The content of hydroxypropylmethylcellulose is 0.1 to 0.8 W / V%, preferably 0.2 to 0.7 W / V%, more preferably 0.2 to 0.5 W / V% in the ophthalmic composition. If the content of the component (C) is less than 0.1 W / V%, the intended ocular drying treatment effect can not be exhibited. On the other hand, when it exceeds 0.8 W / V%, blur after the application of the ink is observed.

(D) Polyvinylpyrrolidone

The weight average molecular weight of the polyvinylpyrrolidone is preferably 30,000 (g / mol) or more from the viewpoint of exerting an effect of ocular drying treatment, and 1.5,000,000 (g / mol) or less from the viewpoint of preventing blur desirable. More preferably 10 to 1.3 million (g / mol), and still more preferably 80 to 1.2 million (g / mol). Further, the weight average molecular weight is measured by a GPC-MALLS system.

The content of polyvinylpyrrolidone in the ophthalmic composition is preferably 0.01 W / V% or more, more preferably 0.5 W / V% or less from the viewpoint of further preventing ocular dryness treatment . More preferably 0.02 to 0.3 W / V%, and still more preferably 0.03 to 0.2 W / V%.

In the present invention, the combination of (C) hydroxypropylmethylcellulose and (D) a specific water-soluble polymer compound called polyvinylpyrrolidone improves the effect of ocular drying treatment and prevents blurring after an eye drop. Methyl cellulose, polyvinyl alcohol, or the like, the desired effect can not be obtained. In addition, by the above combination, it is possible to exhibit the stability of vitamin A and the ocular drying treatment effect even when the content of (B) the nonionic surfactant is in the low range of 0.05 to 1.5 W / V%.

(C): (D) is preferably from 1.5: 1 to 30: 1, more preferably from 4: 1 to 20: 1, and still more preferably from 5: 1 to 10: 1. When (C) hydroxypropylmethylcellulose is added to (D) polyvinylpyrrolidone 1 at a ratio of 1.5 or more, the effect of preventing blurring after the application of the composition is further exerted. When the amount is 30 or less, the effect of dry eye treatment is further exerted.

The total amount of the component (C) and the component (D) is preferably 0.11 to 1.3 W / V%, more preferably 0.15 to 1.3 W / V% and still more preferably 0.23 to 0.7 W / V%.

The ophthalmic composition of the present invention can be compounded with various components incorporated in the ophthalmic composition within the range not impairing the effect of the present invention. These components include polyhydric alcohols, buffers, lubricants, antioxidants, sugars, pH adjusting agents, preservatives, isotonic agents, stabilizers, refreshing agents, drugs and water. Each of these may be used alone or in combination of two or more, and an appropriate amount may be added.

Examples of polyhydric alcohols include glycerin, propylene glycol, butylene glycol, and polyethylene glycol. The content of the polyhydric alcohol in the ophthalmic composition is preferably 0.01 to 5 W / V%, more preferably 0.05 to 3 W / V%.

Examples of the buffering agent include buffers such as boric acid or its salts such as borax, citric acid or its salts such as sodium citrate, phosphoric acid or its salts such as sodium monohydrogen phosphate, tartaric acid or its salts such as sodium tartrate, (Such as sodium gluconate), acetic acid or its salt (such as sodium acetate), low-irritation among them, and trometamol from the standpoint of preservative effect of the composition. In addition, when boric acid and borax are used in combination, a particularly high preservative effect is obtained. The content of the buffering agent is preferably 0.001 to 10 W / V%, more preferably 0.01 to 5 W / V% in the ophthalmic composition. From the viewpoint of improving the storage stability of vitamin A, it is preferable to blend trometamol.

Examples of the viscosifier include hydroxyethylcellulose, methylcellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, polyacrylic acid, and carboxyvinyl polymer. The content of the viscosifying agent is preferably 0.5 W / V% or less, and may not be blended.

By adding an antioxidant, the storage stability of vitamin A is improved. Examples of the antioxidant include d-? -Tocopherol, d-? -Tocopherol, d-? -Tocopherol, d-? -Tocopherol, dl-? -Tocopherol, d-? -Tocopherol acetate, dl-? Vitamin E such as? -tocopherol, dl-? -tocopherol acetate, dl-? -tocopherol acetate and dl-? -tocopherol nicotinate, oil-soluble antioxidants such as dibutylhydroxytoluene and butylhydroxyanisole, vitamin C, And water-soluble antioxidants such as hydroquinone, cysteine and glutathione. The content of the antioxidant in the ophthalmic composition is preferably 0.005 to 5 W / V%, more preferably 0.005 to 1 W / V%, and still more preferably 0.005 to 0.2 W / V%.

Examples of the saccharides include glucose, cyclodextrin, xylitol, sorbitol and mannitol. They may be any of a D-form, an L-form, and a DL-form. The content of saccharides in the ophthalmic composition is preferably 0.001 to 10 W / V%, more preferably 0.005 to 5 W / V%, and still more preferably 0.01 to 3 W / V%.

As the pH adjusting agent, it is preferable to use an inorganic acid or an inorganic alkaline agent. Examples of the inorganic acid include (heme) hydrochloric acid. Examples of the inorganic alkaline agent include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogencarbonate and the like. Among them, hydrochloric acid, sodium hydroxide and potassium hydroxide are preferable. The pH (20 캜) of the ophthalmic composition is preferably from 3.8 to 8.0, more preferably from 5.0 to 7.5. In the present invention, the pH is measured at 20.degree. C. using a pH-permeation meter (for example, HOSM-1, DKK-TOA CORPORATION, etc.). The content of the pH adjuster is appropriately selected according to the intended pH range, but is preferably 0.00001 to 10 W / V%, more preferably 0.0001 to 5 W / V%, still more preferably 0.001 to 3 W / V%.

Examples of the preservative include benzalkonium chloride, benzethonium chloride, sorbic acid or salts thereof, paraoxybenzoic acid esters (such as methylparaben, ethylparaben, propylparaben), chlorhexidine gluconate, thimerosyl, phenylethyl alcohol, Diaminoethylglycine, polyhexanedic acid hydrochloride, polydronium chloride, and the like. Sorbic acid or a salt thereof is preferable from the viewpoint of an ocular dry treatment effect. The content of the preservative is, for example, 0.00001 to 5 W / V%, preferably 0.0001 to 3 W / V%, and more preferably 0.001 to 2 W / V% in the ophthalmic composition. Preservatives may also be noncultivated because they may aggravate the symptoms of dry eye. When the preservative-free formulation is used, the buoyant force may be combined with one or more, suitably two or more kinds of combinations from sodium edetate, boric acid and trometamol. Further, even when the container is equipped with a unit capacity container and a filter, no preservative can be mixed.

Examples of the isotonic agent include sodium chloride and potassium chloride. The content of the isotonic agent relative to the total amount of the ophthalmic composition is, for example, 0.001 to 5 W / V%, preferably 0.01 to 3 W / V%, more preferably 0.1 to 2 W / V%.

Examples of the stabilizer include sodium edetate, cyclodextrin, sulfite, and dibutylhydroxytoluene. The content of the stabilizer in the ophthalmic composition is, for example, 0.001 to 5 W / V%, preferably 0.01 to 3 W / V%, more preferably 0.1 to 2 W / V%.

Examples of the refreshing agent include menthol, camphor, borneol, geraniol, linalool, cineol and the like. The content of the refreshing agent is preferably from 0.0001 to 5 W / V%, more preferably from 0.001 to 2 W / V%, still more preferably from 0.005 to 1 W / V%, still more preferably from 0.007 to 0.8 W / V% is particularly preferable.

Examples of the drug (pharmaceutically active ingredient) include decongestants (for example, naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylhexrine hydrochloride, epinephrine, ephedrine hydrochloride, dl-methylphedrine hydrochloride, Naphthol, etc.), antiseptics and astringents (e.g. neostigmine methyl sulfate,? -Aminocaproic acid, allantoin, berberine chloride, zinc sulfate, zinc lactate, lysozyme chloride, dipotassium glycyrrhizinate, ammonium glycyrrhizinate, (For example, hydrochloric acid dipropylamine hydrochloride, diphenhydramine hydrochloride, isopentyl hydrochloride, chlorpheniramine maleate, etc.), and the like. water-soluble vitamins (active-form vitamin B _2, vitamin B _6, vitamin B _12), amino acids (e. g., L- aspartic acid, potassium, magnesium L- aspartic acid, aminoethyl sulfonic acid, (Sodium dodecyl sulfate, sodium droitin sulfate, etc.), sulfatase, bactericides (e.g., sulfur, isopropylmethylphenol, hinokitiol, etc.), antiallergic agents (cromoglycic acid, fentanyl ketotifen, tranilast, etc.) (For example, lidocaine, lidocaine hydrochloride, procaine hydrochloride, and dibucaine hydrochloride), an antidote (cyclopentolate hydrochloride, tropicamide and the like), and a cataract treatment agent (pyrrenoxine, glutathione, etc.).

The content of these components is appropriately selected depending on the kind of the preparation, the kind of the drug, etc., and the content of the various components is known in the art. For example, it can be appropriately selected from the range of 0.0001 to 30 W / V%, preferably 0.001 to 10 W / V% based on the total amount of the ophthalmic composition. More specifically, the content of each component in the ophthalmic composition is as follows.

For example, from 0.0001 to 0.5 W / V%, preferably from 0.0005 to 0.3 W / V%, more preferably from 0.001 to 0.1 W / V%.

For example, 0.0001 to 10 W / V%, preferably 0.0001 to 5 W / V%.

For example, it is 0.0001 to 10 W / V%, preferably 0.001 to 5 W / V% if it is an antihistamine agent.

Soluble vitamin is 0.0001 to 1 W / V%, preferably 0.0001 to 0.5 W / V%.

Amino acid is 0.0001 to 10 W / V%, preferably 0.001 to 3 W / V%.

For example, 0.00001 to 10 W / V%, preferably 0.0001 to 10 W / V%.

For example, it is 0.0001 to 10 W / V%, preferably 0.001 to 5 W / V% if it is an antiallergic agent.

For example, 0.001 to 1 W / V%, preferably 0.005 to 1 W / V% in the case of a therapeutic agent for local anesthetics, astringent agent and cataract.

The ophthalmic composition of the present invention may be prepared in the form of a liquid, a suspension, a gel or the like. Specific examples of the mode of use include eyedrops (for example, general eye drops, eyedrops for contact lenses, etc.), eyelashes (general cleansers, cleansers used after separating contact lenses, etc.), contact lens mounting solutions, And a separation liquid. Among them, contact lens users are liable to dry ocularly. Therefore, the ophthalmic composition of the present invention is suitable as an eye drop for a contact lens, a cleanser used after separating a contact lens, a contact lens mounting liquid, and a contact lens separation liquid. Particularly, since the amount of the preservative is limited, it is particularly preferable to use for a soft contact lens.

The viscosity of the ophthalmic composition of the present invention is preferably 2.5 to 120 mPa · s, more preferably 6 to 60 mPa · s. The viscosity is measured at 20 캜 using an E-type viscometer (for example, VISCONICELD-R, TOKYO KEIKI INC., Etc.).

The method for preparing the ophthalmic composition of the present invention is not particularly limited. For example, it can be prepared by dissolving (A) vitamin A in (B) sterilized purified water (the remainder) with a nonionic surfactant, Drug, other ingredients, and a cooling agent are added in this order) to adjust the pH. Thereafter, it can be filled aseptically in a suitable container, for example, a container made of polyethylene terephthalate.

Polyethylene, polyethylene terephthalate and other pillow packaging, such as oxygen-adsorption pillow packaging by improving the stability of vitamin A further. Oxygen-adsorbed pillow packaging is a pillow that can actively remove oxygen remaining in the pillow and oxygen that invades from the outside, using a film containing an oxygen absorbent.

The ophthalmic composition of the present invention is suitable as an ocular-drying therapeutic agent, and its effect can be exerted by dropping 30 to 60 쨉 l once or three to six times a day.

Example

Hereinafter, the present invention will be described in detail with reference to examples and comparative examples, but the present invention is not limited to the following examples. Unless otherwise specified, "% " of the composition is " W / V% mass% ", and the ratio indicates a mass ratio.

[Examples 1 to 27, Comparative Examples 1 to 9]

(A) Retinol palmitate ester was solubilized in purified water with (B) polyoxyethylene (200) polyoxypropylene (70) glycol, and another compounding ingredient was added thereto to prepare an ophthalmic composition ). The viscosity of the obtained ophthalmic composition was measured at 20 캜 by VISCONIC ELD-R (manufactured by TOKYO KEIKI INC.) And evaluated in the following manner. The results are listed in the table.

Test Example 1

(Ocular dry evaluation test using rabbit corneal epithelial injury model)

[Corneal and conjunctival wound healing effects]

Healing effect of corneal and conjunctival injuries using heptanol-treated rabbit cornea and conjunctival epithelial injury model

The rabbits were treated with heptanol (200 μl of heptanol / ethanol = 8: 2 mixed solution, 200 μl on one eye) to give a model in which rabbit corneal epithelium and conjunctival epithelium were impaired. Thereafter, the sample was not examined consecutively for 11 days [6 times (100 쨉 l / times) / day]. During the instillation period, fluororesin staining (50 μl of 2% fluororesin in one eye) was periodically performed, and the healing effects of corneal and conjunctival injuries were evaluated according to the Lenp criteria. The score was 15 points (score after heptanol treatment was 15 points And the score decreases as the improvement progresses). The results of the evaluation on the fifth day are shown. Ocular drying is defined as "leakage of various substances and chronic diseases of each conjunctival epithelium, accompanied by eye discomfort or visual function abnormality." The corneal and conjunctival epithelial injury models used in this test were evaluated for ocular dryness . The results are shown in the following evaluation criteria.

<Evaluation Criteria>

◎: 6 points or more and less than 8 points

○: 8 points or more and less than 10 points

△: 10 points or more and less than 12 points

×: 12 points or more

Test Example 2

(Blurred test after instillation)

Five panelists took a sample of 2 drops and observed 1m from the place 5m away from the point of instillation 5m (HANDAYA CO., LTD HP-1226A international standard illusive visual acuity chart 5M) . The results are shown in the following evaluation criteria based on the average value of five persons.

<Rating>

5: Not clouded

4: A little cloudy

3: Somewhat blurred

2: fairly cloudy

1: very cloudy

<Evaluation Criteria>

◎: Average point is 4 points or more

○: Average point is 3 or more and less than 4 points

?: Average point is 2 or more and less than 3 points

X: Average point is less than 2 points

When the component (B) is below the lower limit, the oil component can not be solubilized and is separated. In this case, since the concentration of the useful ingredient is not fixed, it is expected that the effect becomes uneven or blurring after the application of the eye drops becomes worse, so that evaluation can not be conducted.

Further, the following evaluation was conducted.

Test Example 3

&Lt; Retention rate (%) of retinol palmitate >

15 mL of the ophthalmic composition was filled in a 15 mL polyethylene terephthalate container. Pillow packing (5 × 10 cm, pillow packing product), oxygen absorption pillow packing (oxygen absorption pillow packing article). The oxygen absorbing pillow was cut into an oxygen absorbing film: High-Star O ₂ (Starplastic Industry Inc.) and made to have a size of 5 x 10 cm with a heat sealer. This was stored at 40 ° C and 75% RH for 6 months. Retinol palmitate content in ophthalmic compositions was measured immediately after preparation and after 6 months of storage at 0 占 폚 and 75% RH. The measurement was carried out using a high-performance liquid chromatography method. Based on the obtained retinol palmitate content, the retention percentage (%) of retinol palmitate was calculated based on the following formula. The results are shown in Table 6 below.

Retinol palmitate retention (%)

= Retinol palmitate content after storage / retinol palmitate content immediately after preparation × 100

The raw materials used in preparing Examples and Comparative Examples are shown below.

Polyoxyethylene (200) Polyoxypropylene (70) Glycol:

UNILUB 70DP-950B, NOF CORPORATION, or Lutrol F127, BASF Japan Ltd.

· Hydroxypropylmethylcellulose (hypromelose):

metolose 60SH-4000, Japan Pharmacopoeia, Shin-Etsu Chemical Co., Ltd., weight average molecular weight 300,000 (g / mol)

metolose 60SH-50, Shin-Etsu Chemical Co., Ltd., Japan Pharmacopoeia, weight average molecular weight 70,000 (g / mol)

Polyvinylpyrrolidone:

Kollidon 90F, Japan Pharmacopoeia, BASF Japan Ltd. .: Weight average molecular weight 1 million (g / mol), Tables 1 to 4 used

Kollidon 30, Japan Pharmacopoeia, BASF Japan Ltd. .: Weight average molecular weight 50,000 (g / mol)

· Polyoxyethylene monooleate (20) Sorbitan (Polysorbate 80):

RHEODOL TW-0120V, Japanese Pharmacopoeia, Kao Corporation

Polyoxyethylene hydrogenated castor oil 60:

HCO-60 (for medical use), approx., Nikko Chemicals Co., Ltd.

Polyvinyl alcohol:

Gohsenol EG-05, The Nippon Synthetic Chemical Industry Co., Ltd.

Methylcellulose:

metolose SM-4000, Japan Pharmacopoeia, Shin-Etsu Chemical Co., Ltd.

Claims (8)

(A) Vitamin A,
(B) 0.05 to 1.5 W / V% of a nonionic surfactant,
(C) 0.1 to 0.8 W / V% of hydroxypropyl methylcellulose, and
(D) a polyvinyl pyrrolidone. The method according to claim 1,
(C): (D) is in the range of 1.5: 1 to 30: 1. 3. The method according to claim 1 or 2,
And the content of the component (D) is 0.01 to 0.5 g / 100 mL. 4. The method according to any one of claims 1 to 3,
(A) is at least one member selected from the group consisting of retinol palmitate, retinol acetate, and retinoic acid. 5. The method according to any one of claims 1 to 4,
(B) is at least one member selected from polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, and polyoxyethylene sorbitan fatty acid ester. 6. The method according to any one of claims 1 to 5,
(C) hydroxypropylmethylcellulose has a weight average molecular weight of 5-60,000 (g / mol). 7. The method according to any one of claims 1 to 6,
(D) polyvinylpyrrolidone has a weight average molecular weight of 3 to 1.5 million (g / mol). 8. The method according to any one of claims 1 to 7,
Wherein the composition is an ocular-drying therapeutic agent.