JP2006219475A - Ocular locally applying preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a locally applying preparation improving the wetting property of contact lenses and increasing the amount of tear liquid. <P>SOLUTION: This ocular locally applying preparation containing (a) alginic acid or its salt and (b) menthol and/or camphor is provided by improving the wetting property of the contact lenses, increasing the amount of the tear liquid and exhibiting an effect of moistening eyes. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a preparation for topical ocular application such as eye drops and eye wash.

  In order to wear a contact lens accurately and safely on the cornea that is always wet with tear fluid and to make wearing for a long time comfortable, it is desirable that the material of the contact lens is hydrophilic and the surface is easily wetted. However, hard contact lenses and oxygen permeable hard contact lenses are essentially hard to wet because they are based on hydrophobic polymethyl methacrylate and polysiloxanyl methacrylate, respectively. In the case of soft contact lenses, a hydrophilic material with high moisture content is used, so that it is easy to get wet, but adsorption of proteins and lipids is remarkable, and these substances adhere with the use of contact lenses. As it accumulates, the wettability of the soft contact lens surface deteriorates.

  In order to wear a contact lens comfortably, a sufficient amount of tears is indispensable, but the thickness of the lens is about 100 μm, even though the thickness of the lens is usually 100 μm. Since it is only about 7 μm, it is not easy to keep the contact lens wet with tears. In addition, as described above, when the wettability of the contact lens is poor, it becomes more difficult to stably cover the surface of the contact lens placed in the thin tear film with the tear liquid. If the lens surface cannot be sufficiently wetted by tears, dry eyes and discomfort during wearing occur. Furthermore, drying of the contact lens surface can damage the conjunctiva and cornea due to mechanical friction or the like, and can cause ocular tissue damage.

  As described above, any type of contact lens has a problem that the wettability of the surface of the contact lens is a problem due to the nature of the material and adhering matter, which causes damage to the eye tissue during wearing and wearing. . In order to solve this problem, an ophthalmic composition having a sufficient water wetting effect regardless of the material of the contact lens is desirable. Furthermore, it is desirable that the lacrimation is promoted because the contact lens can be sufficiently wetted.

  By the way, keratoconjunctival epithelial disorder caused by dry eye, that is, qualitative or quantitative abnormality of tears, is a problem regardless of whether or not a contact lens is worn. Contact lens wearers in particular are prone to severe corneal epithelial damage. Therefore, for the treatment of dry eye, it is important to supply tear fluid to the dry eye, to supply tear fluid during contact lens wearing, and to stabilize the tear fluid layer.

Polyoxyethylene polyoxypropylene glycol and polyoxyethylene polyoxypropylene-substituted ethylenediamine are already known as ophthalmically safe surfactants that have no adverse effects such as accumulation in contact lenses, and use their washing and wetting effects. A contact lens cleaning agent is disclosed (Patent Document 1). Further, a method for enhancing water wetting of a soft contact lens containing terpenoid as an active ingredient and an ophthalmic composition thereof are known (Patent Document 2). Furthermore, in the ophthalmic composition with adjusted viscosity, which contains polyoxyethylene polyoxypropylene glycol and a thickening agent and has a viscosity at 20 degrees of 1 cps or more and 8 cps or less, It is known that the contact lens is excellent in the effect of improving water, and the contact lens has a continuous water-wetting effect (Patent Document 3).
JP-A-4-313721 JP-A-11-130667 WO97 / 28827

  Then, this invention makes it a subject to provide the ophthalmic topical preparation which promotes lacrimation and improves the wettability of a contact lens.

  As a result of intensive studies for solving the problems, the present inventors have found that by containing a) alginic acid and b) menthol and / or camphor, it is possible to provide a topical preparation with improved contact lens water wetting. The present invention has been completed. Further, it has been found that such a topical preparation increases the amount of lacrimal secretion and moisturizes the eyes, and is useful for the prevention or treatment of dry eye.

The present invention has been developed based on such findings.
That is, the present invention includes the following inventions:
(1) a topical ophthalmic preparation containing a) alginic acid or a salt thereof, and b) menthol and / or camphor,
(2) The ophthalmic topical preparation according to (1), further comprising one or more compounds selected from borneol, geraniol, cineol, linalyl acetate or menthone,
(3) Further, it contains one or more nonionic surfactants selected from polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene sorbitan fatty acid esters or polyoxyethylene hydrogenated castor oils. (1) or (2) topical ocular preparation,
(4) The topical ophthalmic preparation described in (1) to (3), wherein the viscosity at 20 ° C. is 1.2 to 1000 mPa · s or less,
(5) An ophthalmic topical preparation according to any one of (1) to (4), which is an eye drop, an eye wash, or a contact lens mounting liquid,
(6) A topical ophthalmic preparation according to any one of (1) to (5), which is an eye drop for contact lenses, a contact lens mounting solution, and an eye wash for contact lenses;
(7) The ophthalmic topical preparation according to any one of (1) to (6), having a pH of 4.0 to 10.0,
(8) The topical ophthalmic preparation described in (1), which is for soft contact lenses,
(9) A method for improving the wettability of a contact lens by applying a topical ophthalmic preparation containing a) alginic acid or a salt thereof and b) menthol and / or camphor to the contact lens.
(10) A method of suppressing adsorption of menthol and / or camphor to a contact lens by including a) alginic acid or a salt thereof, and b) menthol and / or camphor in a topical ophthalmic preparation.
(11) The method according to (9) or (10), which is a soft contact lens.
(12) A method in which a) alginic acid or a salt thereof, and b) menthol and / or camphor are included together in a topical ophthalmic preparation to enhance the effect of increasing the lacrimal secretion of the preparation.
In the present specification, unless otherwise specified,% means w / v%. Further, in the present specification, the term “contact lens” is used to include all types of contact lenses such as hard, oxygen-permeable hard, soft, and color.

  The topical ophthalmic preparation of the present invention improves the wettability of contact lenses, increases the amount of tears, moisturizes the eyes, and is excellent in improving dry eye symptoms. In addition, the contact lens to which the topical ophthalmic preparation of the present invention is applied is easily wetted, the water wettability is maintained, the tear film is stabilized, and the adhesion of dirt can be prevented. In the present invention, the wettability of the contact lens is improved and the amount of tears is increased. Therefore, the contact lens can be worn comfortably, and discomfort such as a foreign body sensation can be eliminated. The ophthalmic topical preparation of the present invention can be used as an ophthalmic topical preparation for treating dry eyes or improving dry eyes. Moreover, the ophthalmic topical preparation of the present invention can be used as an ophthalmic topical preparation for improving the wettability of contact lenses. Furthermore, adsorption of menthol and / or camphor on contact lenses can be suppressed by including alginic acid or a salt thereof in the topical ophthalmic preparation.

  As the alginic acid or a salt thereof in the present invention, either a natural product or a synthetic product may be used. Typical natural products include Macrocystis on the west coast of the United States, Lessonia in Chile in South America, Ascophyllum in Scandinavia, etc. The extraction method includes an alkali extraction method, but is not particularly defined. Further, the mannuronic acid / guluronic acid ratio (M / G ratio) is not particularly defined, and a wide range of alginic acid from M-rich to G-rich can be used, but is preferably 4.0 or less. More preferably, it is 3.0 or less, More preferably, it is 2.5 or less, Most preferably, it is 2.0 or less. Here, examples of the alginic acid salt include sodium salt, potassium salt, triethanol salt, and ammonium salt of alginic acid. Of these, sodium alginate and potassium alginate are preferable. Alginic acid or a salt thereof can be used as a commercial product, and is commercially available from Kibun Food Chemifa Co., Ltd., Kimika Co., Ltd., Fuji Chemical Industry Co., Ltd. and the like.

  The content of alginic acid or a salt thereof in the ophthalmic topical preparation of the present invention can be appropriately set according to the molecular weight, composition (M / G ratio) and other components coexisting in the preparation. 001 to 5%, more preferably 0.005 to 5%, more preferably 0.005 to 1%, still more preferably 0.005 to 0.5%, and particularly preferably 0.01 to 0.5%. is there.

  Menthol and / or camphor in the ophthalmic topical preparation of the present invention may be menthol or camphor alone or in combination with menthol and camphor, but the total amount of these compounds is usually 0.0001 to 5%, preferably 0.0005 to 3%, more preferably 0.007 to 3%, more preferably 0.001 to 3%, still more preferably 0.001 to 2%, particularly preferably 0.005 to It is about 2%, more preferably about 0.01 to 1%. In the case of a contact lens preparation or eye wash, it is more preferable that the upper limit is 0.5%. These may be d-form, l-form or dl-form. These compounds are all known compounds, and commercially available products can be used. Further, menthol and essential oil containing camphor (for example, peppermint oil, eucalyptus oil, etc.) can also be used.

  The ophthalmic topical preparation of the present invention preferably further contains one or more compounds selected from borneol, geraniol, cineol, linalyl acetate or menthone in combination. As a total amount of one or more compounds selected from borneol, geraniol, cineol, linalyl acetate or mentholone with respect to 1 part by weight of menthol and / or camphor, preferably 0.001 to 5 parts by weight, more Preferably it is 0.01-1 weight part, Most preferably, it can be used at about 0.05-0.8 weight part.

  It is preferable that the ophthalmic topical preparation in the present invention further contains a nonionic surfactant. 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 of ethylenediamine such as poloxamine Additives such as POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monooleate (polysorbate 80), POE sorbitan monostearate (polysorbate 60), POE sorbitan tristearate (polysorbate 65), etc. POE sorbitan fatty acid esters; P such as POE hydrogenated castor oil 5, POE hydrogenated castor oil 10, POE hydrogenated castor oil 20, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE hydrogenated castor oil 100 E hydrogenated castor oil; POE (9) POE alkyl ethers such as lauryl ether; POE (20) POP (4) POE / POP alkyl ethers such as cetyl ether; POE (10) POE alkyl phenyl such as nonylphenyl ether And ethers. 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.

  The content of the nonionic surfactant in the preparation for topical application to the eye varies depending on the type of the surfactant and the like, but cannot generally be defined, but is usually 0.0001 to 5%, preferably 0.001 to 1%, More preferably, it is used at about 0.001 to 0.8%, particularly preferably about 0.005 to 0.5%.

  The topical ophthalmic preparation in the present invention preferably further contains a cellulose derivative. Cellulose derivatives that can be used in ophthalmic topical preparations can be used, such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose or pharmacologically acceptable thereof A salt etc. can be mentioned. Among these, at least one selected from methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, or a salt thereof is preferable. Here, examples of the pharmacologically acceptable salt include alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium, and salts with metals such as aluminum.

  The content of the cellulose derivative with respect to the preparation for topical application to the eye varies depending on the molecular weight and type, and thus cannot be specified unconditionally. However, the concentration of the cellulose derivative in the preparation is usually 0.001 to 10%, preferably 0.005 to 5%. %, More preferably 0.01 to 2%, still more preferably 0.05 to 2%, particularly preferably about 0.1 to 2%. In the case of contact lens preparations and eyewashes, it is more preferable that the upper limit is 1%.

  When setting the viscosity of the ophthalmic topical preparation of the present invention, it is usually preferable to design by maintaining the viscosity at 20 ° C. at 1.2 mPa · s or more, usually 1.2 to 1000 mPa · s, preferably 1.2 to 500 mPa · s, particularly preferably 1.5 to 100 mPa · s, and more preferably about 1.5 to 80 mPa · s. In particular, in the case of an eye wash, it is usually designed to be 1 to 100 mPa · s, preferably 1 to 50 mPa · s, more preferably 1 to 30 mPa · s, and still more preferably about 1 to 20 mPa · s.

  The ocular topical preparation of the present invention can be used in various fields such as pharmaceuticals, quasi-drugs, miscellaneous goods, etc., as long as it utilizes the effects of the invention. For example, eye drops (agents) (including eye drops that can be used while wearing contact lenses, also referred to as eye drops), eye wash (agents) (use contact lenses while wearing) And eyewashes), eye ointments, contact lens mounting solutions, and the like. Preferably, it is an ophthalmic topical preparation for contact lenses, and it is used for contact lens eye drops (artificial tears type eye drops), contact lens mounting liquids, and contact lens wears that can be used while wearing contact lenses. Contact lens eyewashes (including eyewashes used by contact lens wearers, including eyewashes with contact lenses and those with contact lenses removed), particularly preferably while wearing contact lenses Eye drops for eyeglasses, eyewashes, and contact lens mounting liquids that can be used for the above. In particular, eye drops, eye washes, and mounting solutions for soft contact lens users are suitable.

  The preparation for topical ophthalmic application of the present invention is particularly suitable for use in contact lenses. Among contact lenses, it is particularly preferable to use for soft contact lenses. Soft contact lenses generally change the water content of the lens by increasing the evaporation of tears and changing the osmotic pressure gradient, compared to hard contact lenses and oxygen-permeable hard contact lenses. For this reason, it is said that the eyes are easy to dry even when the water wetting of the lens does not decrease, and that dry eyes are easily induced. This tendency is high with high water content contact lenses and is therefore more pronounced with Group IV soft contact lenses that are prone to contamination. On the other hand, the soft contact lenses, hard contact lenses, and oxygen permeable hard contact lenses of Group I have low water content but low lens wettability. According to the present invention, not only the wettability of the lens is improved, but also lacrimation is promoted, so that it is possible to increase the amount of tears at the time of wearing any lens and to reduce the dry feeling at the time of wearing. it can. In addition, it is known that menthol and camphor are easily adsorbed to contact lenses, particularly soft contact lenses. Has been. Also from this point, it is preferable to use the ophthalmic topical preparation of the present invention for contact lenses.

The ophthalmic topical preparation of the present invention may contain various components (including pharmacologically active ingredients and physiologically active ingredients) in combination as long as the effects of the present invention are not hindered. The type of such components is not particularly limited, and examples thereof include, for example, 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, and antibacterial agents. Examples include components, bactericidal components, saccharides, polysaccharides or derivatives thereof, water-soluble polymers other than those described above, local anesthetic components, steroid components, and glaucoma therapeutic agents. Examples of suitable components in the present invention include the following components. These may be d-form, l-form or dl-form.
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.
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, etc.
Amino acids: For example, aminoethylsulfonic acid (taurine), glutamic acid, creatinine, potassium aspartate, magnesium aspartate, magnesium / aspartate mixture, sodium glutamate, sodium chondroitin sulfate and the like.
Antibacterial component or bactericidal component: For example, alkylpolyaminoethylglycine, sulfamethoxazole, sulfisoxazole, sulfamethoxazole sodium, sulfisomidine sodium, berberine sulfate, berberine chloride, boric acid and the like.
Sugars: for example, monosaccharides, disaccharides, specifically glucose, trehalose and the like.
Polysaccharides or derivatives thereof: for example, sodium hyaluronate, sodium chondroitin sulfate, etc.
Water-soluble polymers other than those described above: polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, and the like.
Local anesthetic components: for example, oxybuprocaine hydrochloride, cocaine hydrochloride, cornecaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethylaminoethyl parabutylaminobenzoate, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothiocaine hydrochloride, lidocaine hydrochloride.
Steroid component: for example, dexamethasone, hydrocortisone, fluorometholone, prednisolone, methylprednisolone, hydroxymesterone, hydrocortisone caproate, prednisolone caproate, cortisone acetate, hydrocortisone acetate, prednisolone acetate, sodium dexamethasone metasulfobenzoate, sodium dexamethasone sulfate Dexamethasone sodium phosphate, triamcinolone acetonide, betamethasone sodium phosphate, dexamethasone sodium metasulfobenzoate, methylprednisolone and the like.

  The compounding amounts of these components in the ophthalmic topical preparation are appropriately selected according to the type of formulation, the type of active ingredient, and the like, and the compounding amounts of various components are known in the art. For example, it can be selected from the range of about 0.0001 to 30%, preferably about 0.001 to 10% with respect to the whole preparation. More specifically, the content of each component is, for example, as follows for the ophthalmic composition.

Decongestant component (vasoconstrictor or sympathomimetic drug): For example, 0.0001 to 0.5%, preferably 0.0005 to 0.3%, more preferably 0.001 to 0.1%.
Eye muscle modulator component: For example, 0.0001 to 0.5%, preferably 0.0005 to 0.1%, more preferably 0.0005 to 0.01%.
Anti-inflammatory component or astringent component: for example, 0.0001-10%, preferably 0.0001-5%.
Antihistamine component or antiallergic agent component: for example, 0.0001 to 10%, preferably 0.001 to 5%.
Vitamins: For example, 0.0001 to 1%, preferably 0.0001 to 0.5%.
Amino acids: For example, 0.0001 to 10%, preferably 0.001 to 3%.
Antibacterial component or bactericidal component: For example, 0.00001 to 10%, preferably 0.0001 to 10%.
Saccharides: For example, 0.0001 to 5%, preferably 0.001 to 5%, more preferably 0.01 to 2%.
Polysaccharide or derivative thereof: for example, 0.0001 to 2%, preferably 0.01 to 2%, more preferably 0.01 to 1%.
Water-soluble polymers other than those described above: For example, 0.001 to 10%, preferably 0.001 to 5%, more preferably 0.01 to 3%.
Local anesthetic component: For example, 0.001-1%, preferably 0.01-1%.
Steroid component: For example, 0.001 to 1%, preferably 0.01 to 1%.

  In addition, in the ophthalmic topical preparation of the present invention, various components and additives are appropriately selected according to conventional methods according to the use and form as long as the effects of the invention are not impaired. May be used in combination. 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 cooling agents can be mentioned.

Although the typical component used for the ophthalmic topical preparation of this invention is illustrated below, it is not limited to these.
Thickener: For example, dextran, carboxyvinyl polymer, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol, sodium chondroitin sulfate and the like.
Sugars: for example, glucose, cyclodextrin and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like.
These may be d-form, l-form or dl-form.
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 antibacterials: 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.), Glowyl (product of Rhodia) Name) etc.
pH adjusting agent: for example, hydrochloric acid, boric acid, aminoethylsulfonic 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.
Stabilizer: Dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, etc.
Solubilizer, base: octyldodecanol, titanium oxide, potassium bromide, paraffin, castor oil, sesame oil, plastibase, lanolin, petrolatum, etc.

Thickener: 0.0005 to 50%, for example, preferably 0.001 to 10%
Saccharides: for example 0.001 to 10%, preferably 0.01 to 5%
Surfactant: For example, 0.0001 to 10%, preferably 0.005 to 5%
Preservative, bactericidal agent or antibacterial agent: for example, 0.00001-5%, preferably 0.0001-2%
pH regulator: for example, 0.00001-5%, preferably 0.0001-2%
Isotonizing agent: for example 0.001 to 10%, preferably 0.01 to 5%

  The ophthalmic topical preparation 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 0.3 to 4.1, preferably 0.3 to 2. 1, particularly preferably about 0.5 to 1.4.

The ophthalmic topical preparation 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 pH 4.0 to 10.0, preferably 4.5 to 9.5, particularly preferably 5.0 to 9.0. Adjustment of pH can be performed using a buffer, the said pH adjuster, etc.
Here, examples of the buffer include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, and acetate buffer. Preferred buffering agents are borate buffer, phosphate buffer, carbonate buffer and citrate buffer. Particularly preferred buffering agents are borate buffers or phosphate buffers. Examples of the boric acid buffer include borates such as boric acid, alkali metal borates, and alkaline earth metal borates, and combinations of boric acid and borates. Examples of the phosphate buffer include phosphates such as phosphoric acid, alkali metal phosphates, and alkaline earth metal phosphates, and combinations of phosphoric acid and phosphates. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. More specifically, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, etc.), phosphoric acid or a salt thereof (sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, etc.) , Carbonic acid or a salt thereof (sodium bicarbonate, sodium carbonate, etc.), citric acid or a salt thereof (sodium citrate, potassium citrate, etc.). When a borate buffer or a phosphate buffer is used as the buffer, the concentration of these buffers in the ophthalmic topical preparation of the present invention is, for example, about 0.0001 to 10.0%.

  The ocular topical preparation of the present invention can be produced by a known method. Semi-solid and liquid preparations can be prepared by mixing the base and each component. Furthermore, if necessary, a filtration sterilization treatment process, a container filling process, and the like can be added.

  Also included is a method for improving the wettability of a contact lens by applying a topical ophthalmic preparation containing a) alginic acid or a salt thereof, and b) menthol and / or camphor to the contact lens when worn. Furthermore, the method includes a method of suppressing adsorption of menthol and / or camphor to a contact lens by including a) alginic acid or a salt thereof and b) menthol and / or camphor in a topical ophthalmic preparation. Furthermore, a method for enhancing the effect of increasing the lacrimal secretion amount of a preparation for topical ocular application is also included. In addition, regarding alginic acid or its salt, menthol, and camphor contained, it can carry out according to the above-mentioned description regarding the ocular topical preparation of the present invention.

  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.

Test Example 1 Contact lens wettability improvement test test preparation was prepared.
Test preparation 1: 0.005 g menthol, 0.35 g borax, 1.8 g boric acid, 0.05 g polysorbate 80, purified water / hydrochloric acid / sodium hydroxide are added in appropriate amounts to a total volume of 100 ml (pH = 7.5). It was set as the test formulation.
Test preparation 2: 0.005 g camphor, 0.35 g borax, 1.8 g boric acid, 0.05 g polysorbate 80, purified water / hydrochloric acid / sodium hydroxide are added in appropriate amounts to a total volume of 100 ml (pH = 7.5). It was set as the test formulation.
Test preparation 3: 0.1 g alginic acid, 0.005 g menthol, 0.35 g borax, 1.8 g boric acid, 0.05 g polysorbate 80, purified water / hydrochloric acid / sodium hydroxide were added in appropriate amounts to a total volume of 100 ml ( The test preparation was pH = 7.5).
Test preparation 4: 0.1 g alginic acid, 0.005 g camphor, 0.35 g borax, 1.8 g boric acid, 0.05 g polysorbate 80, purified water / hydrochloric acid / sodium hydroxide were added in appropriate amounts to a total volume of 100 ml ( The test preparation was pH = 7.5).
Test formulation 5: 0.1 g alginic acid, 0.025 g menthol, 0.025 g borneol, 0.35 g borax, 1.8 g boric acid, 0.05 g polysorbate 80, purified water / hydrochloric acid / sodium hydroxide. Appropriate amount was added to obtain a test preparation having a total amount of 100 ml (pH = 7.5).

  5 μl of test preparations 1 to 5 are dropped on the soft contact lens and the oxygen permeable hard contact lens, and 10 seconds later, the portion where the droplet is in contact with the acrylic plate surface and the top of the droplet are focused from the side of the digital camera. Shoot with. This operation was repeated 5 times for the same test preparation. The contact angle of the droplet in contact with the contact lens surface was measured using image analysis software.

  As a result of the test, it was confirmed that the wettability of the soft contact lens and the oxygen permeable hard contact lens was remarkably improved in the test formulations 3, 4 and 5 as compared with the test formulations 1 and 2. In addition, in Test preparations 3 and 4, it was confirmed that adsorption of menthol or camphor on the contact lens was suppressed. Test preparation 5 was particularly remarkable.

Test Example 2 Tear Volume Measurement Test The test preparation 5 was filtered and filled in an eye drop container, and the eye drop of the test preparation 3 was applied to subjects (10 subjects) who have not used the eye drop or eye wash for 30 minutes or longer. The tear volume before and after application was measured. For the measurement of the amount of tears, a phenol red thread (Showa Yakuhin Kogyo Co., Ltd.) was sandwiched between lower eyelids, and after 15 seconds, the length of the part where the phenol red thread was taken out and turned red was measured to determine the amount of tears. Immediately after measuring the tear volume of each subject, the subject was instilled with the eye drops of the test preparation 3 in both eyes, and the tear volume was measured again 5 minutes after the instillation, and the average value of both eyes was measured before and after the instillation. Compared.

  As a result of the test, an increase in tear volume was observed in 9 out of 10 subjects instilled with test preparation 5, and 1 in 10 subjects did not change. Therefore, it was confirmed that the preparation for topical ocular application of the present invention has an effect of increasing the amount of lacrimal secretion.

Test Example 3 Moistness Sensation Test The prepared test preparation is filtered and filled into an eye drop container to produce an eye drop for use in the test, and the eye drop is used for 20 dedicated monitors (10 naked eyes, 5 oxygen-permeable hard contact lens wearers) 5 people who wear soft contact lenses) and evaluated the moist feeling. After instilling one drop of eye drop (Test preparation 1 or 2) in both eyes, 30 minutes later (Test preparation 3 or 4) is instilled into both eyes, and the eye drops containing no alginic acid and alginic acid previously instilled are added. We compared the feeling of moisturization with the eye drops containing it and asked them to evaluate which of the eye drops felt moist.

As a result of the test, when test preparations 1 and 3 were compared, all of the monitors evaluated that test preparation 3 (an eye drop containing alginic acid) was moistened. In comparison between test preparations 2 and 4, all the monitors evaluated that test preparation 4 (an eye drop containing alginic acid) was moistened.

Test Example 4 Soft Contact Lens Wettability Improvement Test Each example shown in Tables 1 to 10 is described as a unit of g / 100 mL.
About each Example of Tables 1-10, the contact angle on a soft contact lens was measured according to the method of the test example 1 contact lens wettability improvement test. The contact angle is indicated in the table as ◎ when the contact angle is 65 ° or less, ◯ when the contact angle is greater than 65 and 75 ° or less, and Δ when the contact angle is greater than 75 °.

Test Example 5 Eyewash Test For each of the eyewashes described in Tables 3, 4 and 5, 10 monitors (soft contact lens wearers) engaged in VDT work in the daytime using an eyewash at 7:00 pm The feeling of use was confirmed. Before the eye wash, the soft contact lens was removed and washed, and then the soft contact lens was worn again. The results are shown in the table. When the moist feeling immediately after wearing the lens is judged, ◎ when the monitor judged to have a good moist feeling is 8 or more out of 10 ◎ when 6 or more out of 10 people, ○ out of 10 The case where it is less than or equal to the name is indicated by Δ

Test Example 6 Soft Contact Lens Wearing Test Soft contact lens wearing liquid 3 described in Table 8 was tested. 10 monitors (soft contact lens wearers) engaged in VDT work in the daytime removed the soft contact lens at 7:00 pm and applied 2 drops on the lens from which the soft contact lens mounting solution 3 described in Table 8 was removed. After that, I had the eye wear again. When the moist feeling immediately after wearing the lens was determined, all 10 monitors determined that the moist feeling was good.

Claims (11)

An ophthalmic topical preparation containing a) alginic acid or a salt thereof, and b) menthol and / or camphor. The ophthalmic topical preparation according to claim 1, further comprising one or more compounds selected from borneol, geraniol, cineol, linalyl acetate or menthone. The composition further comprises one or more nonionic surfactants selected from polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene sorbitan fatty acid esters or polyoxyethylene hydrogenated castor oils. Or ocular topical preparation according to 2. The preparation for topical ophthalmic application according to any one of claims 1 to 3, which has a viscosity at 20 ° C of 1.2 to 1000 mPa · s. The ophthalmic topical preparation according to any one of claims 1 to 4, which is an eye wash or a contact lens mounting solution. The ophthalmic topical preparation according to any one of claims 1 to 5, which is an eye drop for contact lenses, a contact lens mounting solution, and an eye wash for contact lenses. The ophthalmic topical preparation according to any one of claims 1 to 6, which has a pH of 4.0 to 10.0. The ophthalmic topical preparation according to claim 1, which is used for soft contact lenses. A method for improving the wettability of a contact lens by applying a topical ophthalmic preparation containing a) alginic acid or a salt thereof and b) menthol and / or camphor to the contact lens. A method of suppressing adsorption of menthol and / or camphor to a contact lens by including a) alginic acid or a salt thereof, and b) menthol and / or camphor together with a topical ophthalmic preparation. The method according to claim 9 or 10, which is a soft contact lens.