JP2012072183A - Refreshing composition for ophthalmology - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a refreshing composition for ophthalmology, capable of imparting a sufficient refreshing effect even when soft contact lenses are worn.SOLUTION: The refreshing composition for ophthalmology for imparting the refreshing effect when the soft contact lenses are worn can be provided, which contains compounds especially selected from menthol, camphor or borneol in refrigerants singly or in combination in the total amount in a limited range of ≥0.01 w/v% and <0.1 w/v%, and inorganic salts as essential components besides them, and further contains a specified polymer having a specific molecular weight in combination therewith.

Description

  The present invention relates to an ophthalmic refreshing composition that can be applied to the eye during wearing of a soft contact lens, and can give a sufficient refreshing feeling even when the soft contact lens is worn.

  In the ophthalmic refreshing composition, a refreshing agent represented by menthol is blended. It is important to formulate a refreshing agent so that a comfortable and refreshing feeling can be imparted without unpleasant stimuli. It is necessary to administer menthol at a high concentration enough to give a refreshing feeling of moderate strength even if it is worn. However, an excessively high concentration of menthol is accompanied by an unpleasant irritation that exceeds the refreshing feeling immediately after instillation, so that the amount of menthol that can be blended in the ophthalmic cooling composition is naturally limited.

  Therefore, in ophthalmic refreshing compositions, eye drops and contact lens mounting liquids containing terpenoids, water-soluble polymers (such as hydroxypropylmethylcellulose) and local anesthetics (such as chlorobutanol) give a good refreshing feeling. It is known that the refreshing feeling is sustained and the irritation is low (Patent Document 1). In addition, a method of maintaining a refreshing feeling while suppressing eye irritation by blending camphor and borneol at a certain ratio or more with respect to menthol is disclosed, and menthol stimulation with an upper limit of 0.015 w / v% is disclosed. It can be relaxed (Patent Document 2).

  Thus, a method for maintaining sufficient refreshing feeling and improving menthol irritation without simply increasing the amount of a refreshing agent such as menthol. However, these methods and eye drops have been developed mainly for the purpose of providing a refreshing feeling to users who are not wearing soft contact lenses, that is, users who regularly use the naked eye or hard contact lenses. No particular consideration is given to the specific problems in wearing soft contact lenses.

By the way, there are the following unique problems in wearing soft contact lenses.
The cornea is a tissue rich in sensory nerves, and the nerve density in the corneal epithelium is said to be about 300 to 600 times that of the skin. (Non-Patent Document 1). Therefore, whether or not the user feels a refreshing feeling is affected by how much menthol touches the corneal surface. The diameter of the hard contact lens is smaller than the diameter of the cornea, and even when the hard contact lens is worn, the peripheral edge of the cornea is exposed. However, when the soft contact lens diameter is larger than the cornea and the soft contact lens is worn, the cornea surface is soft contacted. Covered with a lens. Therefore, a soft contact lens wearer is less likely to feel a refreshing feeling as compared with the case of naked eyes.
In addition, when the soft contact lens is worn, the tear fluid exchange rate between the rear surface of the lens (corneal side) and the portion not covered by the lens (conjunctival surface) is extremely reduced. In the hard contact lens, the tear exchange rate at the best fitting shows a high value of 25.6 ± 11.1 (% / min), which is similar to the tear exchange rate in the tear meniscus of normal eyes. Even the lacrimal fluid exchange rate of 16.5 ± 1.1 (% / min) shows a low value (Non-Patent Document 2 Decrease in the rate of lacrimal fluid exchange with the lens). Therefore, tear exchange for menthol to reach the center of the cornea via the tear film in the gap between the soft contact lens and the eye surface is extremely slow, which increases the sensitivity reduction of the refreshing sensation.

Until now, even when applied to an eye wearing a soft contact lens, an ophthalmic refreshing composition capable of imparting a sufficient refreshing feeling has not been known. Also, few methods are known for promoting tear exchange on the rear surface of the lens while wearing a soft contact lens. As described above, it has been extremely difficult to alleviate the stimulus while maintaining the required refreshing feeling for a certain period of time while wearing the soft contact lens.
Furthermore, refreshing agents such as menthol, local anesthetics such as chlorobutanol, preservatives such as quaternary ammonium salts such as benzalkonium chloride, vasoconstrictors such as tetrahydrozoline hydrochloride, naphazoline hydrochloride, and naphazoline nitrate The formulation design is limited when it contains components that are likely to adversely affect (adsorption or deformation) the soft contact lenses.

JP 2003-183157 A JP-A-9-132526

Literature on corneal surface perception New ophthalmology, 4 (1), p11-20, 1987 Journal of Japanese Contact Lens Society 45 (1), p1-10, 2003

  Then, this invention makes it a subject to provide the refreshing composition which can provide a sufficient refreshing feeling even if it wears a soft contact lens.

  As a result of intensive studies for solving the problems, the present inventors a) compounds selected from menthol, camphor or borneol, in a total amount of 0.01 (w / v)% or more and 0.1 (w / v) less than%, b) inorganic salts, and c) hydroxyethyl cellulose having an average molecular weight of 200,000 to 2.5 million, methyl cellulose having an average molecular weight of 50,000 to 500,000, polyvinyl pyrrolidone having an average molecular weight of 10,000 to 150,000, an average molecular weight At least one selected from at least one selected from 50,000 to 500,000 chondroitin sulfate or a salt thereof, hydroxypropyl methylcellulose having an average molecular weight of 50,000 to 500,000, and polyvinyl alcohol having an average molecular weight of 10,000 to 300,000 The ophthalmic refreshing composition it contains gives a refreshing feeling without irritation even when applied to the eye when wearing soft contact lenses. It found that can be, and have completed the present invention.

The present inventor has been developed based on such knowledge.
That is, the present invention is an ophthalmic refreshing composition listed in the following (1) to (12).
(1) a) a compound selected from menthol, camphor or borneol, in a total amount of 0.01 w / v% or more and less than 0.1 w / v%,
b) inorganic salts, and c) hydroxyethyl cellulose having an average molecular weight of 200,000 to 2.5 million, methyl cellulose having an average molecular weight of 50,000 to 500,000, polyvinylpyrrolidone having an average molecular weight of 10,000 to 150,000, and an average molecular weight of 50,000 to 50 Software comprising at least one selected from 10,000 hydroxypropyl methylcellulose, polyvinyl alcohol having an average molecular weight of 10,000 to 300,000, chondroitin sulfate having an average molecular weight of 50,000 to 500,000 or a salt thereof A refreshing ophthalmic composition for imparting a refreshing sensation when wearing contact lenses,
(2) The ophthalmic refreshing composition according to (1), wherein hydroxyethyl cellulose having an average molecular weight of 200,000 to 2.5 million is contained at 0.001 to 10 w / v%,
(3) A refreshing composition for ophthalmic use according to (1), comprising methylcellulose having an average molecular weight of 50,000 to 500,000 at 0.001 to 10 w / v%,
(4) A cool composition for ophthalmic use according to (1), which contains polyvinylpyrrolidone having an average molecular weight of 10,000 to 150,000 at 0.001 to 10 w / v%,
(5) Oxygen refreshing composition as described in (1) which contains hydroxypropyl methylcellulose having an average molecular weight of 50,000 to 500,000 at 0.001 to 10 w / v%,
(6) The cool composition for ophthalmic use according to (1), which contains polyvinyl alcohol having an average molecular weight of 10,000 to 300,000 at 0.001 to 10 w / v%,
(7) The ophthalmic refreshing composition according to (1), containing chondroitin sulfate having an average molecular weight of 50,000 to 500,000 or a salt thereof at 0.001 to 10 w / v%,
(8) Furthermore, the ophthalmic refreshing composition as described in (1) thru | or (7) which contains 0.001-5 w / v% of nonionic surfactant,
(9) The ophthalmic refreshing composition according to any one of (1) to (8), further containing 0.0001 to 1 w / v% of edetic acid or a salt thereof,
(10) Further, at least one component selected from aminoethyl sulfonic acid, glutamic acid, potassium aspartate, magnesium aspartate, sodium glutamate, glucose or trehalose is added in a total amount of 0.01 to 5 w / v%. The ophthalmic refreshing composition according to (1) to (9),
(11) The ophthalmic refreshing composition according to any one of (1) to (10), which is an eye drop or an eye wash.
(12) a) A compound selected from menthol, camphor or borneol, in a total amount of 0.01 w / v% or more and less than 0.1 w / v%,
b) inorganic salts, and c) hydroxyethyl cellulose having an average molecular weight of 200,000 to 2.5 million, methyl cellulose having an average molecular weight of 50,000 to 500,000, polyvinylpyrrolidone having an average molecular weight of 10,000 to 150,000, and an average molecular weight of 50,000 to 50 Software comprising at least one selected from 10,000 hydroxypropyl methylcellulose, polyvinyl alcohol having an average molecular weight of 10,000 to 300,000, chondroitin sulfate having an average molecular weight of 50,000 to 500,000 or a salt thereof A refreshing ophthalmic composition for contact lens users.
In the present specification, unless otherwise specified,% means w / v%.

According to the ophthalmic cooling composition of the present invention, among the cooling agents, in particular, a compound selected from menthol, camphor or borneol, alone or in combination, is added in a total amount of 0.01 w / v% or more and 0.1 w / Soft contact characterized by containing an inorganic salt as an essential component after containing it within a limited range of less than v%, and further containing a specific polymer having a specific molecular weight in combination. An ophthalmic refreshing composition for imparting a refreshing feeling when wearing a lens can be provided.
Until now, artificial eye drops have been widely used as eye drops applied during soft contact lens wearing. In conventional artificial tear-type eye drops, even if you want to give a sufficient refreshing sensation, menthol and other refreshing agents are adsorbed on soft contact lenses, which is a safety hazard and contains a high concentration of menthol. I couldn't. Even if the amount of menthol is increased by solving the problem of adsorption, the eyes wearing soft contact lenses are not exposed to the cornea and the rate of tear fluid exchange is reduced. It was difficult to give a refreshing feeling.
According to the ophthalmic refreshing composition of the present invention, a sufficient refreshing feeling is obtained immediately after the composition is applied to the eye, and the irritation is alleviated, so that a pleasant refreshing feeling is imparted to the soft contact lens wearer. An ophthalmic refreshing composition can be provided. Furthermore, according to this invention, even if it uses a small amount of menthol, a sufficient refreshing feeling can be provided, and the ophthalmic refreshing composition without irritation and high safety | security can be provided.
Furthermore, since the ophthalmic refreshing composition of the present invention can feel a refreshing feeling without being stimulated by a refreshing agent, for example, a soft contact lens addict who has become an eye that has a disorder due to wearing a soft contact lens, for example. It can be used not only during wearing of the soft contact lens but also as an ophthalmic refreshing composition for soft contact lens users for imparting a refreshing feeling to the eye after the soft contact lens is removed.

  The cool composition for ophthalmology of the present invention contains one or more compounds selected from menthol, camphor or borneol in a total amount of 0.01% or more and less than 0.1%. The lower limit is preferably 0.012% or more, more preferably 0.014% or more, particularly preferably 0.016% or more, and the upper limit is preferably 0.08% or less, more preferably 0.06% or less, Particularly preferably, it is 0.04% or less. If it is less than 0.01%, it is difficult to feel a sufficient refreshing feeling immediately after the composition is applied to the eye, and if it is 0.1% or more, a refreshing feeling immediately after the composition is applied to the eye is strong, and it is warped depending on the user. This is not preferable because it may cause irritation. These compounds are known compounds, and commercially available ones can be used, and either d-form or l-form can be used.

  The ophthalmic refreshing composition of the present invention contains inorganic salts as essential components. Such inorganic salts include sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, disodium hydrogen phosphate, sodium dihydrogen phosphate. And potassium dihydrogen phosphate. Among these, potassium chloride, calcium chloride, sodium chloride, sodium bicarbonate, sodium carbonate, magnesium sulfate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate are preferable, and potassium chloride and sodium chloride are particularly preferable. .

  In the present invention, these inorganic salts in the ophthalmic cooling composition can be used alone or in combination of two or more, and the content thereof is preferably 0.01 to 10%, more preferably as the total amount of inorganic salts. Is 0.1 to 10%, particularly preferably about 0.1 to 5%. If the inorganic salt is less than 0.01%, it is difficult to feel a sufficient refreshing feeling immediately after the composition is applied to the eye, and if it is 10 (w / v)% or more, the refreshing feeling immediately after the composition is applied to the eye is strong. There is a tendency to become too much and some users may feel irritation.

  In the ophthalmic refreshing composition of the present invention, it is essential to contain a specific polymer having a specific molecular weight in combination. That is, in the present invention, hydroxyethylcellulose having an average molecular weight of 200,000 to 2.5 million, methylcellulose having an average molecular weight of 50,000 to 500,000, polyvinylpyrrolidone having an average molecular weight of 10,000 to 150,000, and an average molecular weight of 50,000 to 500,000. It contains at least one selected from hydroxypropylmethylcellulose, polyvinyl alcohol having an average molecular weight of 10,000 to 300,000, chondroitin sulfate having an average molecular weight of 50,000 to 500,000 or a salt thereof.

Hydroxyethyl cellulose used in the present invention is a known polymer compound and has an average molecular weight of 200,000 to 2,500,000, more preferably 500,000 to 2,000,000, particularly preferably 800,000 to 1,500,000. Use. Commercially available hydroxyethyl cellulose can be used, for example, HEC-CF-G (average molecular weight of about 400,000) and HEC-CF-H (average molecular weight of about 700,000) sold by Sumitomo Seika Co., Ltd. , HEC-CF-V (average molecular weight about 1 million), HEC-CF-W (average molecular weight about 1.3 million), HEC-CF-X (average molecular weight about 1.5 million), HEC-CF-Y (average molecular weight about 180 Can be used.
In the present invention, the content of hydroxyethyl cellulose in the ophthalmic cool composition is preferably 0.001 to 10%, more preferably 0.005 to 5%, and particularly preferably about 0.01 to 3%.

Methyl cellulose used in the present invention is a known polymer compound and has an average molecular weight of 50,000 to 500,000. More preferably, methylcellulose having an average molecular weight of 100,000 to 500,000 and particularly preferably 200,000 to 500,000 is used. Commercially available methylcellulose can be used. For example, SM-15 (average molecular weight of about 70,000), SM-25 (average molecular weight of about 90,000) sold by Shin-Etsu Chemical Co., Ltd. as the Metrows SM series. ), SM-50 (average molecular weight of about 110,000), SM-100 (average molecular weight of about 120,000), SM-400 (average molecular weight of about 170,000), SM-1500 (average molecular weight of about 290,000), SM-4000 (Average molecular weight of about 360,000) can be used.
In the present invention, the content of methylcellulose in the ophthalmic cool composition is preferably 0.001 to 10%, more preferably 0.005 to 5%, and particularly preferably about 0.01 to 3%.

Polyvinyl pyrrolidone used in the present invention is a known polymer compound and has an average molecular weight of 10,000 to 150,000. More preferably, polyvinylpyrrolidone having an average molecular weight of 20,000 to 150,000 is used. Commercially available polyvinyl pyrrolidone can be used. For example, Kollidon 25 (average molecular weight of about 30,000), Kollidon 30 (average molecular weight of about 50,000), sold by BASF Corporation as the Kollidon series, Kollidon 17PF (average molecular weight of about 90,000), Kollidon 90 (average molecular weight of about 120,000), etc. can be used.
In the present invention, the content of polyvinylpyrrolidone in the ophthalmic cool composition is preferably 0.001 to 10%, more preferably 0.01 to 5%, and particularly preferably about 0.1 to 3%.

Hydroxypropyl methylcellulose used in the present invention is a known polymer compound and has an average molecular weight of 50,000 to 500,000. More preferred is hydroxypropylmethylcellulose having an average molecular weight of 100,000 to 500,000, particularly preferably 200,000 to 500,000. Commercially available hydroxypropylmethylcellulose can be used, for example, 60SH-15 (average molecular weight of about 70,000), 60SH-25 (average molecular weight of about 70,000 sold by Shin-Etsu Chemical Co., Ltd. as the Metrows SH series. 90,000), 60SH-50 (average molecular weight of about 110,000), 60SH-100 (average molecular weight of about 120,000), 60SH-400 (average molecular weight of about 170,000), 60SH-1500 (average molecular weight of about 290,000), 60SH- 4000 (average molecular weight of about 360,000) can be used.
In the present invention, the content of hydroxypropylmethylcellulose in the ophthalmic cool composition is preferably 0.001 to 10%, more preferably 0.005 to 5%, and particularly preferably about 0.01 to 3%.

The polyvinyl alcohol used in the present invention is a known polymer compound, and an average molecular weight of 10,000 to 300,000 is used. More preferably, polyvinyl alcohol having an average molecular weight of 20,000 to 200,000, particularly preferably an average molecular weight of 20,000 to 150,000 is used. Commercially available polyvinyl alcohol can be used. For example, GOHSENOL EG05 (average molecular weight of about 30,000), GOHSENOL EG40 (average molecular weight of about 120,000) sold by Nippon Synthetic Chemical Co., Ltd. as Gohsenol series. ) Etc. can be used.
In the present invention, the content of polyvinyl alcohol in the ophthalmic cool composition is preferably 0.001 to 10%, more preferably 0.01 to 5%, and particularly preferably about 0.1 to 3%.

Chondroitin sulfate or a salt thereof used in the present invention is a known polymer compound and has an average molecular weight of 50,000 to 500,000. More preferably, chondroitin sulfate or a salt thereof having an average molecular weight of 50,000 to 100,000, particularly preferably 50,000 to 40,000 is used. As such chondroitin sulfate or a salt thereof, commercially available products can be used. For example, sodium chondroitin sulfate (average molecular weight of about 10,000, average molecular weight of about 20,000, average molecular weight of about 4 sold by Seikagaku Corporation) In addition, sodium chondroitin sulfate (average molecular weight of about 7,000, etc.) sold by Maruha Corporation can be used.
In the present invention, the content of chondroitin sulfate or a salt thereof in the ophthalmic refreshing composition is preferably 0.001 to 10%, more preferably 0.01 to 5%, and particularly preferably about 0.05 to 3%. is there.

  The refreshing effect of the present invention becomes remarkable when a nonionic surfactant is blended.

  As the nonionic surfactant used in the present invention, those that can be used by those skilled in the art for an ophthalmic refreshing composition can be used. For example, polyoxyethylene (hereinafter also referred to as POE) -polyoxypropylene ( Hereinafter also referred to as POP.) Block copolymer (for example, poloxamer 407, poloxamer 235, poloxamer 188, etc.); POE-POP block copolymer adduct of ethylenediamine such as poloxamine; POE (20) sorbitan monolaurate (polysorbate 20), mono POE sorbitan fatty acid esters such as oleic acid POE (20) sorbitan (polysorbate 80), POE sorbitan monostearate (polysorbate 60), POE sorbitan tristearate (polysorbate 65); POE hydrogenated castor oil 5, POE hydrogenated castor oil 10 , POE hard POE hydrogenated castor oils such as castor oil 20, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE hydrogenated castor oil 100; POE alkyl ethers such as POE (9) lauryl ether; POE ( 20) POE / POP alkyl ethers such as POP (4) cetyl ether; POE alkyl phenyl ethers such as POE (10) nonylphenyl ether. The numbers in parentheses indicate the number of added moles.

  Among them, nonionic surfactants selected from polyoxyethylene-polyoxypropylene block copolymers, POE sorbitan fatty acid esters or POE hydrogenated castor oils are preferable, and polyoxyethylene-polyoxypropylene blocks are particularly preferable. Copolymer, polysorbate 80, polyoxyethylene hydrogenated castor oil 60.

  In the ophthalmic refreshing composition of the present invention, the content of the nonionic surfactant varies depending on the type of the surfactant and the like, and thus cannot be defined unconditionally, but is usually 0.001 to 5%, preferably 0.001 to 1. %, More preferably about 0.005 to 0.5%.

  The refreshing effect of the present invention becomes more prominent when edetic acid or a salt thereof is added to the ophthalmic refreshing composition. Further, it becomes more prominent when edetic acid or a salt thereof and a nonionic surfactant are combined.

  Examples of such edetic acid or a salt thereof include edetic acid (ethylenediaminetetraacetic acid, EDTA), ethylenediaminediacetic acid (EDDA), diethylenetriaminepentaacetic acid (DTPA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), and the like. Can be illustrated. These may be used alone or in combination, and may be used as a pharmacologically or physiologically acceptable salt (for example, sodium ethylenediaminetetraacetate). Among them, ethylenediaminetetraacetic acid or a salt thereof is preferable, for example, ethylenediaminetetraacetic acid disodium, ethylenediaminetetraacetic acid disodium dihydrate (hereinafter also referred to as sodium edetate).

  The content of edetic acid or a salt thereof in the ophthalmic refreshing composition of the present invention varies depending on the molecular weight, type, etc., and thus cannot be defined unconditionally, but is preferably 0.0001 to 1%, more preferably 0.0005 to 0.00. 5%, particularly preferably about 0.001 to 0.3%.

  The refreshing effect of the present invention is obtained by adding at least one component selected from aminoethylsulfonic acid (taurine), glutamic acid, potassium aspartate, magnesium aspartate, sodium glutamate, glucose or trehalose to the ophthalmic refreshing composition. When it is blended, it becomes more prominent. In this case, it becomes more prominent when blended in combination with the above-described edetic acid or a salt thereof or a nonionic surfactant.

  The total amount of these components in the ophthalmic cool composition of the present invention is preferably 0.01 to 5%, particularly preferably about 0.05 to 3%.

In the ophthalmic refreshing composition of the present invention, it is desirable to design an appropriate viscosity from the viewpoint of imparting a refreshing feeling. The viscosity at 20 ° C. is preferably designed to be 2 to 100 mPa · s, more preferably 2 to 80 mPa · s, and particularly preferably about 2 to 50 mPa · s. The lower limit is preferably designed to be 2 mPa · s or more, and the upper limit of the viscosity exceeding 100 mPa · s tends not to provide a refreshing feeling immediately after instillation.
Viscosity is measured by a method using a cone-and-plate rotational viscometer (general test method, 45. Viscosity measurement method, second method rotational viscometer method described in the 14th revised Japanese pharmacy method, “(3) conical -The method described in the section "Plate type rotational viscometer"). As an example, a TVE-20L viscometer cone plate type (manufactured by TOKIMEC, Toki Sangyo (Japan)), which is a type of E-type viscometer, can be measured under the following measurement conditions. it can.
The standard cone rotor (α = 1 ° 34 ', radius (R) = 2.4 cm) attached to the TVE-20L viscometer cone plate type is rotated by a motor through a spring with a full-scale torque of 67.37 x 10 ^-6 Nm. Let During measurement, the viscometer is installed so that the rotation axis is perpendicular to the horizontal plane. 1 ml of the test sample is placed on a predetermined plate position of the cone rotor and left to stand until the temperature reaches 20 ° C. Next, the apparatus is rotated at a rotational speed corresponding to the viscosity of the test sample, and after 4 minutes, the displayed viscosity is read. In order to obtain highly accurate measurement results, before measurement of the test sample, petroleum-based hydrocarbon oil (Newtonian fluid) specified by JIS Z 8809 is used as the calibration standard solution, and the measured value is the viscosity of the standard solution. Adjust to match. The rotor used at the time of measurement, the number of rotations, the amount of sample to be measured, etc. can be selected as appropriate.

The ophthalmic refreshing composition of the present invention is not particularly limited as long as it is applied to an eye wearing a soft contact lens or a user of a soft contact lens, but an eye drop (eye drop), an eye wash (Eyewash) is preferred.
The soft contact lens to which the ophthalmic refreshing composition of the present invention can be used can be used regardless of the curve shape, edge shape, material, etc. of the soft contact lens. Provide sufficient refreshing feeling to any soft contact lens classified as Group I to Group IV according to the soft contact lens classification method in the examination of soft contact lenses and soft contact lens disinfectants by the Safety Bureau Can do. For example, non-hydrated soft contact lenses, Group I (Medalist / registered trademark, Bushrom Japan Co., Ltd.), Group II (Menicon Soft S / registered trademark, Menicon Corporation), Group III (High Flow Ace / registered trademark, HOYA Healthcare) Soft contact lenses such as Group IV (2 Week Accuview / registered trademark, Johnson & Johnson Co., Ltd.).

The ophthalmic refreshing composition of the present invention is suitable for containing various components (including pharmacologically active components and physiologically active components) in combination. Examples thereof include a decongestant component, an eye regulator component, an anti-inflammatory component or an astringent component, an antihistamine component or an antiallergic component, vitamins, amino acids, saccharides and the like that are commonly used in ophthalmic refreshing compositions. Specifically, the following components can be exemplified.

Decongestant: For example, α-adrenergic agonists, specifically epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, oxymetazoline hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, epinephrine hydrogen tartrate, naphazoline nitrate. These may be d-form, l-form or dl-form.
Eye muscle modulator component: For example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically, neostigmine methyl sulfate, tropicamide, atropine sulfate helenien, and the like.
Anti-inflammatory component or astringent component: for example, zinc sulfate, zinc lactate, allantoin, epsilon-aminocaproic acid, indomethacin, lysozyme chloride, silver nitrate, pranoprofen, sodium azulenesulfonate, dipotassium glycyrrhizinate, diclofenac sodium, bromfena Sodium chloride, berberine chloride, berberine sulfate, etc.
Antihistamine component or antiallergic agent component: for example, acitazanolast, amlexanox, ibudilast, tranilast, diphenhydramine hydrochloride, levocabastine hydrochloride, ketotifen fumarate, sodium cromoglycate, pemirolast potassium, chlorpheniramine maleate, and the like.
Vitamins: for example, retinol acetate, retinol palmitate, pyridoxine hydrochloride, flavin adenine dinucleotide sodium, pyridoxal phosphate, cyanocobalamin, panthenol, calcium pantothenate, sodium pantothenate, ascorbic acid, tocopherol acetate and the like.
Local anesthetic ingredients: for example, chlorobutanol, oxybuprocaine hydrochloride, cocaine hydrochloride, cornecaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethylaminoethyl parabutylaminobenzoate, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothiocaine hydrochloride, hydrochloric acid Lidocaine etc.

  In addition, in the ophthalmic refreshing composition of the present invention, various components and additives are appropriately selected according to conventional methods according to the application and form within a range not impairing the effects of the invention, and one or more are used in combination. And may be contained. As those components or additives, for example, carriers (water, aqueous solvents, aqueous or oily bases, etc.) commonly used in the preparation of semi-solids and liquids, thickeners, sugars, surfactants, Various additives such as preservatives, bactericides or antibacterial agents, pH regulators, tonicity agents, fragrances or refreshing agents, and buffering agents can be mentioned.

Although the typical component used for the ophthalmic refreshing composition of this invention below is illustrated, it is not limited to these.
Thickener: For example, carboxyvinyl polymer, alginic acid or a salt thereof, macrogol, sodium hyaluronate, xanthan gum, sodium carboxymethylcellulose, glycerin, dextran, propylene glycol alginate and the like.
Sugars: for example, glucose, cyclodextrin, trehalose and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like.
Surfactant: For example, glycine-type amphoteric surfactant such as alkyldiaminoethylglycine; alkyl quaternary ammonium salt (specifically, cationic surfactant such as benzalkonium chloride, benzethonium chloride, etc.) The number indicates the number of moles added.
Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, etc.), Glow Kill (manufactured by Rhodia) Name) etc.
pH adjuster: For example, hydrochloric acid, boric acid, epsilon-aminocaproic acid, acetic acid, sodium hydroxide, sodium hydrogen carbonate, sodium carbonate, borax, triethanolamine, monoethanolamine and the like.
Isotonizing agents: for example, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, dihydrogen phosphate Sodium, sodium dihydrogen phosphate, potassium dihydrogen phosphate, glycerin, propylene glycol and the like.
Perfume or refreshing agent: For example, geraniol, camphor, borneol, geraniol, camphor, fennel oil, cool mint oil, spearmint oil, peppermint water, peppermint oil, peppermint oil, bergamot oil, eucalyptus oil, rose oil, etc. . These may be d-form, l-form or dl-form.
Stabilizer: Dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, etc.

  The cool composition for ophthalmology of the present invention can appropriately contain various components and additives as described above, and can be used alone or in combination of two or more, but is exclusively applied when wearing a soft contact lens. Therefore, parahydroxybenzoic acid esters such as chlorobutanol (1,1,1-trichloro-2-methyl-2propanol), benzalkonium chloride (alkylbenzyldimethylammonium chloride), methylparaben, ethylparaben, propylparaben, butylparaben, etc. , Tetrahydrozoline hydrochloride, Naphazoline hydrochloride, Naphazoline nitrate, Phenylephrine hydrochloride, dl-Methylephedrine hydrochloride, Epinephrine, Epinephrine hydrochloride, etc. Serious disease When it contains a decongestant that may result in concealment, it is necessary to devise a formulation design. Moreover, it is also possible to make the formulation design substantially free of these components, and in some cases, an ophthalmic refreshing composition substantially free of these components is desirable.

  The ophthalmic refreshing composition of the present invention is used by adjusting to an osmotic pressure within a range acceptable for a living body, if necessary. The osmotic pressure is about 100 to 1200 mOsm, preferably about 100 to 600 mOsm, particularly preferably about 150 to 400 mOsm, and the osmotic pressure ratio with respect to physiological saline is usually 0.4 to 4.1, preferably 0.3 to 2. 1, particularly preferably about 0.5 to 1.4.

  The ophthalmic refreshing composition of the present invention is used by adjusting to an osmotic pressure within a range applicable to a living body, if necessary. The pH is usually from 5.0 to 10.0, preferably from 6.0 to 9.0, particularly preferably from 6.5 to 8.5. The pH can be adjusted using a buffer, the pH adjuster, or the like.

  The ophthalmic refreshing composition of the present invention can be produced by a known method. For example, if it is a liquid agent, a base and each component can be mixed and prepared. Furthermore, if necessary, a filtration sterilization treatment process, a container filling process, and the like can be added.

In addition, since the ophthalmic refreshing composition of the present invention can feel a refreshing feeling without being stimulated by a refreshing agent, for example, soft contact with respect to an eye sensitive to a stimulus having a disorder by wearing a soft contact lens. It can be used as an ophthalmic refreshing composition for giving a refreshing sensation to the eye after the user who uses the lens regularly wears the soft contact lens or removes the soft contact lens.
Among the refreshing agents, in particular, a compound selected from menthol, camphor or borneol alone or in combination is contained within a limited range of 0.01 w / v% or more and less than 0.1 w / v% as a total amount. In addition, it contains inorganic salts as essential constituents, and further contains a specific polymer having a specific molecular weight in combination with a normal contact with a soft contact lens. Even when applied to sensitive eyes, it is possible to provide a composition excellent in feeling of use in which a sufficient refreshing feeling is imparted immediately after application and the irritation is alleviated.

  Hereinafter, the present invention will be described in detail based on test examples and examples, but the present invention is not limited to these examples.

Preparation of Examples and Comparative Examples Preparation of each of the examples and test examples used in the tests followed the formulations shown in Tables 1-6. Specifically, the preparation method of Example 1 described in Table 1 is shown. Hydroxyethyl cellulose (HEC-CF-G) was stirred and dissolved in about 100 mL of purified water (Preparation Solution A). Next, polysorbate 80, l-menthol, d-camphor and d-borneol were stirred and dissolved (conditioning solution B). Sodium edetate and sodium chloride were dissolved in 50 mL of purified water, adjusted solution A and prepared solution B were added, and further purified water was added to adjust pH (pH = 7.4) to a total of 200 ml. Further, according to Example 1, other examples and comparative examples were also prepared.

Cooling feeling test The test solution is aseptically filtered and filled into eye drops 10 ml at a time, and in a dedicated paneler who regularly uses 20 soft contact lenses, while wearing soft contact lenses or with naked eyes (soft contact lenses In the case of instillation immediately after removal), the refreshing feeling was evaluated immediately after instillation, 5 minutes after instillation, and 10 minutes after instillation. The soft contact lens used was a soft contact lens of Group IV (2 Week Accuview (registered trademark), Johnson & Johnson Co., Ltd.).
Each panel was evaluated on a 7-point scale, with 0 points indicating no refreshing feeling and 6 points indicating a sufficiently strong cooling feeling. Similarly, when the eye irritation was not felt at all, the score was 6 points, and when the strong irritation was felt, the score was 7 points. Average the evaluation points of all panelists, and the average value is expressed as 0 to less than 2 points x, 2 points to less than 3 points, △, 3 points to less than 4 points, and 4 points to 6 points or less as ◎. The results are shown in.

  As a result of the test, it was shown that in the examples of the present invention, a sufficient refreshing feeling was obtained immediately after the composition was applied to the eye, and there was no irritation and high safety. In addition, it is known that regular use of soft contact lenses causes a decrease in tears and some kind of damage to the cornea surface. Particularly immediately after removing the soft contact lenses, it is extremely sensitive to a refreshing feeling such as menthol. However, it was confirmed that a sufficient refreshing feeling can be imparted to the extremely sensitive eyes without irritation.

  As a result of the test, it was shown that in the examples of the present invention, a sufficient refreshing feeling was obtained immediately after the composition was applied to the eye, and there was no irritation and high safety. In addition, it is known that regular use of soft contact lenses causes a decrease in tears and some kind of damage to the cornea surface. Particularly immediately after removing the soft contact lenses, it is extremely sensitive to a refreshing feeling such as menthol. However, it was confirmed that a sufficient refreshing feeling can be imparted to the extremely sensitive eyes without irritation.

  As a result of the test, it was shown that in the examples of the present invention, a sufficient refreshing feeling was obtained immediately after the composition was applied to the eye, and there was no irritation and high safety. In addition, it is known that regular use of soft contact lenses causes a decrease in tears and some kind of damage to the cornea surface. Particularly immediately after removing the soft contact lenses, it is extremely sensitive to a refreshing feeling such as menthol. However, it was confirmed that a sufficient refreshing feeling can be imparted to the extremely sensitive eyes without irritation.

  As a result of the test, in Examples of the present invention containing polyvinylpyrrolidone (average molecular weight of about 30,000) or / and polyvinylpyrrolidone (average molecular weight of about 120,000) in combination with sodium chloride, it is sufficient immediately after the composition is applied to the eye. A refreshing sensation was obtained, indicating no irritation and high safety. In addition, it is known that regular use of soft contact lenses causes a decrease in tears and some kind of damage to the cornea surface. Particularly immediately after removing the soft contact lenses, it is extremely sensitive to a refreshing feeling such as menthol. However, it was confirmed that a sufficient refreshing feeling can be imparted to the extremely sensitive eyes without irritation.

  As a result of the test, the examples of the present invention containing polyvinyl alcohol (average molecular weight of about 30,000) or / and polyvinyl alcohol (average molecular weight of about 120,000) in combination with sodium chloride are sufficient immediately after the composition is applied to the eye. A refreshing sensation was obtained, indicating no irritation and high safety. In addition, it is known that regular use of soft contact lenses causes a decrease in tears and some kind of damage to the cornea surface. Particularly immediately after removing the soft contact lenses, it is extremely sensitive to a refreshing feeling such as menthol. However, it was confirmed that a sufficient refreshing feeling can be imparted to the extremely sensitive eyes without irritation.

  As a result of the test, sodium chondroitin sulfate (average molecular weight of about 10,000) or / and sodium chondroitin sulfate (average molecular weight of about 20,000) in combination with sodium chloride are used immediately after the composition is applied to the eye. Sufficient cool feeling was obtained and it was shown that there was no irritation and safety was high. In addition, it is known that regular use of soft contact lenses causes a decrease in tears and some kind of damage to the cornea surface. Particularly immediately after removing the soft contact lenses, it is extremely sensitive to a refreshing feeling such as menthol. However, it was confirmed that a sufficient refreshing feeling can be imparted to the extremely sensitive eyes without irritation.

Claims (6)

a) a compound selected from menthol, camphor or borneol, in a total amount of 0.01 w / v% or more and less than 0.1 w / v%,
b) inorganic salts, and c) hydroxyethyl cellulose having an average molecular weight of 200,000 to 2.5 million, methyl cellulose having an average molecular weight of 50,000 to 500,000, polyvinylpyrrolidone having an average molecular weight of 10,000 to 150,000, and an average molecular weight of 50,000 to 50 Software comprising at least one selected from 10,000 hydroxypropyl methylcellulose, polyvinyl alcohol having an average molecular weight of 10,000 to 300,000, chondroitin sulfate having an average molecular weight of 50,000 to 500,000 or a salt thereof A refreshing ophthalmic composition for imparting a refreshing feeling when wearing contact lenses. Furthermore, the ophthalmic refreshing composition of Claim 1 which contains a nonionic surfactant 0.001-5 w / v%. Furthermore, the refreshing composition for ophthalmics of Claim 1 or 2 which contains edetic acid or its salt 0.0001-1 w / v%. Furthermore, 0.01-5 w / v% as a total amount of at least one component selected from aminoethylsulfonic acid, glutamic acid, potassium aspartate, magnesium aspartate, sodium glutamate, glucose or trehalose is contained. Item 5. The ophthalmic refreshing composition according to Item 1 to 3. The ophthalmic refreshing composition according to claim 1, which is an eye drop or an eye wash. a) a compound selected from menthol, camphor or borneol, in a total amount of 0.01 w / v% or more and less than 0.1 w / v%,
b) inorganic salts, and c) hydroxyethyl cellulose having an average molecular weight of 200,000 to 2.5 million, methyl cellulose having an average molecular weight of 50,000 to 500,000, polyvinylpyrrolidone having an average molecular weight of 10,000 to 150,000, and an average molecular weight of 50,000 to 50 Software comprising at least one selected from 10,000 hydroxypropyl methylcellulose, polyvinyl alcohol having an average molecular weight of 10,000 to 300,000, chondroitin sulfate having an average molecular weight of 50,000 to 500,000 or a salt thereof A refreshing ophthalmic composition for contact lens users.