JP2012144527A - Composition for ophthalmic use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for ophthalmic use, having excellent dry-eye-ameliorative effects.SOLUTION: The composition for ophthalmic use includes: (A) 0.5-2.5 w/v% of castor oil; and (B) 1-5 w/v% of polyoxyethylene castor oil; wherein the mass ratio represented by (B)/(A) is 2 or greater.

Description

  The present invention relates to an ophthalmic composition excellent in dry eye improvement effect.

  The lacrimal fluid present on the corneal surface has an oil layer composed of fat-soluble vitamins such as vitamin A and vitamin E, lipids and the like, and feels dry when the oil layer decreases. Therefore, it is important for dry eyes to replenish oil components. Conventionally, eye drops containing vitamin A and vitamin E and having an effect on dry eyes are known. However, with regard to the oil component, there have been examples in which about 0.1% by mass is blended in an aqueous eye drop, but the dryness of the eyes has not been improved. From the above, an ophthalmic composition having an excellent dry eye improvement effect has been desired.

JP 2008-222638 A

  This invention is made | formed in view of the said situation, and it aims at providing the ophthalmic composition which has the outstanding dry eye improvement effect.

  As a result of intensive studies to achieve the above object, the present inventors have formulated (A) castor oil at 0.5 W / V% or more as an oil component, and (B) polyoxyethylene castor at least twice as much as this. It has been found that a significant dry eye improvement effect can be obtained by blending a specific amount of oil, and the present invention has been made.

Accordingly, the present invention provides the following ophthalmic compositions.
[1]. (A) Castor oil 0.5 to 2.5 W / V% and (B) polyoxyethylene castor oil 1 to 5 W / V%, and the mass ratio represented by (B) / (A) is 2 or more. An ophthalmic composition.
[2]. The ophthalmic composition according to [1], wherein the transmittance at a wavelength of 600 nm is semi-clear to clear of 75% or more.
[3]. The ophthalmic composition according to [1] or [2], which is for contact lenses.
[4]. The ophthalmic composition according to [1], [2] or [3], wherein no preservative is added.
[5]. The ophthalmic composition according to any one of [1] to [4], which is a dry eye improving agent.

  According to the present invention, an ophthalmic composition having a remarkable dry eye improvement effect can be provided.

Hereinafter, the present invention will be described in detail.
The ophthalmic composition of the present invention contains (A) castor oil 0.5 to 2.5 W / V% and (B) polyoxyethylene castor oil 1 to 5 W / V%, and (B) / (A) Is represented by a mass ratio of 2 or more.

(A) Castor oil Castor oil is an oil component. The content thereof is 0.5 to 2.5 W / V% (mass / volume% (g / 100 mL, the same shall apply hereinafter)) in the ophthalmic composition, more preferably 1 to 2.5 W / V%, still more preferably. If the blending amount is too small, the effect of improving dryness becomes insufficient, and if it exceeds 2.5 W / V%, it may become sticky.

(B) Polyoxyethylene castor oil The number of moles of ethylene oxide added to the polyoxyethylene castor oil is preferably 3 to 60, more preferably 10 to 50, still more preferably 20 to 40. When the number of moles of ethylene oxide added is small, formulation may be difficult, and when it is too much, eye irritation may be felt. Polyoxyethylene castor oil and polyoxyethylene hydrogenated castor oil are different components.

  (B) A component can be used individually by 1 type or in combination of 2 or more types, The content is 1-5 W / V% in an ophthalmic composition, More preferably, it is 3-5 W / V%. is there. The content mass ratio represented by (B) / (A), that is, the content of the component (B) with respect to the component (A) is 2 or more. By setting it as such mass ratio, white turbidity can be suppressed and a clear ophthalmic composition can be obtained. In this respect, the ratio is preferably 2.5 or more, and more preferably 3 or more. The upper limit is not particularly limited, and may be 10 or less, preferably 5 or less.

  The “semi-clear to clear composition” in the present invention refers to a composition having a transmittance of 75% or more at a wavelength of 600 nm in Examples described later.

  The preservative can be blended within a range that does not impair the effects of the present invention, but the ophthalmic composition of the present invention preferably contains no preservative containing no preservative from the viewpoint of eye irritation. The antiseptic power when no preservative is added may be one or more, preferably two or more, in combination of sodium edetate, boric acid and trometamol. The contents are 0.01 to 3 W / V%, respectively. Moreover, when it is set as a unit dose container and a container with a filter, it can be set as preservative-free.

  Examples of the preservative include benzalkonium chloride, benzethonium chloride, sorbic acid or a salt thereof, paraoxybenzoic acid ester (methylparaben, ethylparaben, propylparaben, etc.), chlorhexidine such as chlorhexidine gluconate, thimerosal, phenylethyl alcohol, hydrochloric acid Examples thereof include alkyldiaminoethylglycine, polyhexanide hydrochloride, polydronium chloride and the like.

  The ophthalmic composition of the present invention can be blended with an appropriate amount of any one of the following optional components, as long as they do not impair the effects of the present invention. For example, (A) oily components other than castor oil include castor oil, soybean oil, sesame oil, peanut oil, olive oil, almond oil, wheat germ oil, corn oil, rapeseed oil, sunflower oil, refined lanolin and the like. These contents are 0.001-1 W / V% in an ophthalmic composition.

  Surfactants other than the component (B) include polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, glycine-type amphoteric surfactants such as alkyldiaminoethylglycine, and alkyl quaternary. Ammonium salts (specifically, cationic surfactants such as benzalkonium chloride, benzethonium chloride and the like. These contents are preferably 0.0001 to 10 W / V% in the ophthalmic composition, more Preferably it is 0.005-5 W / V%.

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

  Examples of the thickener include polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, polyvinyl alcohol, sodium hyaluronate, sodium chondroitin sulfate, polyacrylic acid, carboxyvinyl polymer, and the like. By blending these, the retention is increased, and the corneal / conjunctival damage healing effect is further improved. The blending amount of the thickening agent is, for example, 0.001 to 10 W / V%, preferably 0.001 to 5 W / V%, and more preferably 0.01 to 3 W / V%.

  Examples of the saccharide include glucose, cyclodextrin, xylitol, sorbitol, mannitol and the like. In addition, these may be any of d-form, l-form, or dl-form. The compounding quantity of saccharides is 0.001-10 W / V%, for example, Preferably it is 0.005-5 W / V%, More preferably, it is 0.01-3 W / V%.

  As the pH adjuster, it is preferable to use an inorganic acid or an inorganic alkali agent. For example, (diluted) hydrochloric acid is mentioned as an inorganic acid. Examples of the inorganic alkaline agent include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like. Among these, hydrochloric acid and sodium hydroxide are preferable. The pH (20 ° C.) of the ophthalmic composition of the present invention is preferably 3.8 to 8.0, more preferably 5.0 to 7.5. The pH is measured at 20 ° C. using a pH osmometer (for example, HOSM-1, Toa DKK Co.). The blending amount of the pH adjuster is, for example, 0.00001 to 10 W / V%, preferably 0.0001 to 5 W / V%, and more preferably 0.001 to 3 W / V%.

  Examples of the isotonic agent include sodium chloride and potassium chloride. The compounding quantity of an isotonizing agent is 0.001-5 W / V%, for example, Preferably it is 0.01-3 W / V%, More preferably, it is 0.1-2 W / V%.

  Examples of the stabilizer include sodium edetate, cyclodextrin, sulfite, dibutylhydroxytoluene and the like. The compounding quantity of a stabilizer is 0.001-5 W / V%, for example, Preferably it is 0.01-3 W / V%, More preferably, it is 0.1-2 W / V%.

  Examples of the refreshing agent include menthol, camphor, borneol, geraniol, cineol, linalool and the like. The content of the refreshing agent is preferably 0.0001 to 5 W / V%, more preferably 0.001 to 2 W / V%, and more preferably 0.005 to 1 W / V% as the total amount of the compound in the ophthalmic composition. Is more preferable, and 0.007 to 0.8 W / V% is particularly preferable.

Examples of drugs (pharmaceutical active ingredients) include decongestants (eg, naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylephrine hydrochloride, epinephrine, ephedrine hydrochloride, dl-methylephedrine hydrochloride, tetrahydrozoline nitrate, naphazoline nitrate), anti-inflammatory / astringents (For example, neostigmine methyl sulfate, ε-aminocaproic acid, allantoin, berberine chloride, zinc sulfate, zinc lactate, lysozyme chloride, dipotassium glycyrrhizinate, ammonium glycyrrhizinate, glycyrrhetinic acid, methyl salicylate, tranexamic acid, sodium azulene sulfonate, etc.) , Antihistamines (eg, iproheptin hydrochloride, diphenhydramine hydrochloride, diphenhydramine, isothipentyl hydrochloride, chlorpheniramine maleate, etc.), antiallergic agents For example, sodium cromoglycate, etc.), water-soluble vitamins (activated vitamin B _2, vitamin B _6, vitamin B _12, etc.), fat-soluble vitamins (vitamin E, vitamin A, etc.), amino acids (e.g., potassium L- aspartic acid, Magnesium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, glutathione, etc.), sulfa drugs, fungicides (eg, sulfur, isopropylmethylphenol, hinokitiol, etc.), local anesthetics (eg, lidocaine, lidocaine hydrochloride, procaine hydrochloride, Dibucaine hydrochloride and the like) and mydriatics (for example, tropicamide and the like) can be appropriately blended.

  Since the ophthalmic composition of the present invention has a remarkable dry eye improvement effect, it is suitable as a dry eye improvement agent and a dry eye treatment agent. Dry eye refers to a state where the keratoconjunctiva on the eyeball surface is damaged due to qualitative or quantitative abnormality of tears. When used as a dry eye improving agent or a dry eye treatment agent, the effect can be more exhibited by instilling 30 to 60 μL at a time, 3 to 6 times a day.

  Further, since the contact lens user tends to dry their eyes and easily becomes dry eyes, the ophthalmic composition of the present invention is also suitable for contact lenses. In the present invention, “for contact lens” means one used during wearing of a contact lens. More specifically, eye drops (including eye drops for contact lenses that can be applied while wearing contact lenses), eye wash (including eye drops for contact lenses that can be washed while wearing contact lenses), contact lens mounting liquids (Used when a contact lens is mounted) and the like, and eye drops, particularly eye drops for contact lenses are preferred. The contact lens is not particularly limited, and examples thereof include hard contact lenses, oxygen-permeable hard contact lenses, soft contact lenses, disposable contact lenses, and silicone hydrogel contact lenses.

  The ophthalmic composition of the present invention is liquid, and the viscosity of the ophthalmic solution is preferably 1 to 50 mPa · s, more preferably 1 to 20 mPa · s, and further preferably 1 to 5 mPa · s. The viscosity is measured at 20 ° C. using an E-type viscometer (for example, VISCONIC ELD-R, Tokyo Keiki Co., Ltd.).

  The preparation method of the ophthalmic composition of the present invention is not particularly limited. For example, an active ingredient and an additive are mixed in water, and a premixed mixture of the components (A) and (B), It can be obtained by blending a refreshing agent and adjusting the pH, and after aseptic filtration, it is filled into a suitable container.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, unless otherwise specified, “%” in the composition represents W (mass) / V (volume)% (g / 100 mL), and the ratio represents a mass ratio.

[Examples 1 to 10, Comparative Examples 1 to 6]
Ophthalmic compositions (eye drops) having the compositions shown in the following table were prepared by a conventional method. The obtained ophthalmic composition (eye drops) was evaluated as follows. The results are also shown in the table. Moreover, pH (20 degreeC) of the ophthalmic composition was performed using the pH osmometer (HOSM-1, Toa DK Corporation), and a result is shown in a table | surface.

[Clarity]
The transmittance | permeability of 600 nm was measured for the sample with the spectrophotometer (Hitachi U-3310). The clarity is shown based on the following evaluation criteria.
<Evaluation criteria>
○: The transmittance is 75% or more ×: The transmittance is 65% or more and less than 75% XX: The transmittance is less than 65%

[Drying improvement effect-1]
For those who complain of dry eye symptoms (severity level 1: The Ocular Surface, Vol 5, No. 2, 2007), 50 μL of ophthalmic composition is instilled (3 times at 2 hour intervals), and the third instillation 30 minutes The degree of subsequent dry eye improvement (eye dryness) was evaluated according to the following evaluation criteria. A result shows the average value (rounded to the first decimal place) of 3 persons.
<Evaluation criteria>
5: Very improved 4: Improved 3: Slightly improved 2: Neither 1: Not improved

[Drying improvement effect-2]
50 μL of an ophthalmic composition is instilled (3 persons) to 3 persons who are soft contact lens wearers and complain of dry eye symptoms (severity level 1: The Ocular Surface, Vol 5, No. 2, 2007). The degree of dry eye improvement (eye dryness) 30 minutes after the third instillation was evaluated according to the following evaluation criteria.
A result shows the average value (rounded to the first decimal place) of three persons.
<Evaluation criteria>
5: Very improved 4: Improved 3: Slightly improved 2: Neither 1: Not improved

ヒプロメロース：メトローズ ６０ＳＨ−４０００（信越化学工業（株））

Hypromellose: Metroles 60SH-4000 (Shin-Etsu Chemical Co., Ltd.)

Claims (5)

  (A) Castor oil 0.5 to 2.5 W / V% and (B) Polyoxyethylene castor oil 1 to 5 W / V%, and the content ratio represented by (B) / (A) is 2 An ophthalmic composition as described above.   The ophthalmic composition according to claim 1, wherein the transmittance at a wavelength of 600 nm is semi-clear to clear of 75% or more.   The ophthalmic composition according to claim 1 or 2, which is used for contact lenses.   The ophthalmic composition according to claim 1, 2 or 3, which contains no preservative.   It is a dry eye improving agent, The ophthalmic composition of any one of Claims 1-4.