JP2021107457A - Ophthalmological composition - Google Patents

Abstract

To provide an ophthalmological composition, stabilizing a tear fluid layer when wearing a contact lens, suppressing dryness of eyes, providing a good use feeling, having excellent convenience, free from the risk of misuse, and having high efficiency at stages from production to sale.SOLUTION: Eye drops for wearing a contact lens contains (A) one or more selected from the group consisting of a cellulosic polymer compound, a vinylic polymer compound, a polyethylene glycol and a dextran, and (B) amino acids.SELECTED DRAWING: Figure 1

Description

The present invention relates to an ophthalmic composition for reducing the effect of contact lenses on the eye, and more specifically, stabilizes the tear film, particularly the oil layer when wearing contact lenses, suppresses a feeling of dryness, and deteriorates visual function. The present invention relates to eye drops worn for contact lenses, which are excellent in preventing the above.

In recent years, contact lenses, especially soft contact lenses (hereinafter, sometimes referred to as SCL), have become remarkably widespread for the purpose of vision correction and cosmetology. However, wearing contact lenses imposes a burden on the eyes, although there are individual differences.
Dry eyes are a typical complaint of contact lens wearers. A healthy tear layer is a thin layer with a thickness of about 7 μm, and has a three-layer structure consisting of a mucus layer, a water layer, and an oil layer from the eyeball side, and protects the cornea from dryness and external stimuli. In particular, this oil layer closest to the outside world prevents tears from evaporating, but due to factors such as the tear layer becoming thin and unstable, the oil layer also tends to become thin, uneven and unstable, and tears. Evaporation of the liquid is promoted, and dry eye symptoms such as dry eyes occur. Due to such destruction (destabilization) of the tear film, spots where the oil layer is extremely thin or absent are generated, and a portion called a dry spot is observed on the surface of the tear film, but it is dry. Dry spots are considered to be one of the important indicators of diagnostic criteria for dry eyes and dry eye, as the time of spot occurrence is used to calculate the tear film breakup time (BUT) (non-spot generation time). Patent Document 1). That is, if it is possible to delay the generation time of dry spots or suppress the spread of the number and area of dry spots when the eyelid opening time is the same, it is possible to suppress dry eye symptoms such as dry eyes and tired eyes. It is considered to be connected and have an important meaning.

Further, it is known that even if the eyes are healthy with the naked eye, when contact lenses are worn, the tear film becomes uneven, the eyes tend to feel dry, and the eyes tend to become dry. Especially during SCL wearing, the tear film on the SCL tends to be very thin, and on the SCL it is often observed that the oil layer is very thin or, in some cases, the oil layer is partially or totally absent. NS. As a result, the evaporation of tears is accelerated, and the water in the SCL and even the water under the SCL are also promoted to evaporate, which may cause "dry eyes" and corneal damage (non-patent documents). 2).
Therefore, in order to ensure the safety of the eyes of contact lens wearers, it is necessary to continuously and effectively stabilize the tear film, particularly the oil layer, on the outer surface of the lens.

Conventionally, a method of instilling artificial tears has been adopted for dry eyes, but a method of simply instilling artificial tears cannot achieve stabilization of the tear layer and is effective. Was not enough. Therefore, a system that stabilizes the tear film around the contact lens by adsorbing polyvinylpyrrolidone on the surface of the ionic contact lens to increase the water retention of the lens surface, and the eye drops and wearing solution for contact lenses used for the system are used. It has been proposed (Patent Document 1). In addition, an ophthalmic solution composition for promoting and maintaining the formation of a three-layer structure of a tear film using a long-chain alkyl derivative of a polysaccharide has also been proposed (Patent Document 2). However, the systems and compositions described in these documents have not always exerted a sufficiently sustained and efficient stabilizing effect on the tear film, especially the oil layer.

Furthermore, another problem associated with wearing contact lenses is a decrease in contrast sensitivity. Contrast sensitivity is one of the visual function evaluation axes, and indicates the ability to discriminate subtle differences in brightness. If the contrast sensitivity is lowered, for example, the contrast between the road surface and the obstacle may be difficult to recognize while walking, leading to an accident, or the contrast between the ball and the background may be difficult to recognize in sports (especially ball games), which may cause inconvenience. .. Conventionally, it has been known that the cause of the decrease in contrast sensitivity is ophthalmic surgery such as corneal refractive surgery using an excimer laser, aging, and wearing of contact lenses. It has been reported that the decrease in contrast sensitivity due to wearing contact lenses is related to wearing bifocal contact lenses, long-term soft contact lenses, and continuous soft contact lenses. However, as a solution to such a problem, there is an attempt to change the contact lens itself, but the improvement of the contrast sensitivity by the ophthalmic composition is not known.

By the way, ophthalmic solutions such as eye drops, eye wash agents, and contact lens wearing solutions basically have different purposes and are treated individually when used. Therefore, the user of the contact lens needs to hold and use the contact lens wearing solution and the eye drop solution separately, for example. However, although these solutions have different purposes (uses), they often have similar appearances due to the dose and the like, and there is a risk of misuse. In addition, there is a risk that the seller may misuse the product due to misunderstanding at the time of guidance or misunderstanding of the product. Therefore, the development of products that can be used easily and safely without misuse has been widely requested not only by users but also by sellers.

New Ophthalmology 22 (3): 279-287, 2005 New Ophthalmology 22 (3): 311-316, 2005 JP 2001-247466 JP-A-2007-77053

As described above, conventionally, ophthalmic solutions such as eye drops and contact lens wearing solutions have been handled individually. Although the individual performance of these preparations has been investigated, the suitability of the combination of the eye drops and the contact lens wearing solution has not been sufficiently examined. Surprisingly, when a contact lens is worn using a conventional contact lens wearing solution and then an eye drop of another formulation is instilled, the present inventors have a sufficient effect of stabilizing the tear film layer and improving eyestrain. It has been found that not only the effect and the effect of improving the contrast sensitivity are not observed, but also an unpleasant feeling of use such as a feeling of stickiness and a feeling of stickiness may occur.
Therefore, the present invention provides an ophthalmic composition that stabilizes the tear film while wearing contact lenses, suppresses dryness of the eyes, eliminates tired eyes and a decrease in contrast sensitivity, and has a good usability. The purpose is to do.
Another object of the present invention is to provide an ophthalmic composition having excellent convenience, no fear of misuse, and high safety.
Furthermore, it is an object of the present invention to provide an ophthalmic composition having high efficiency and safety at all stages from production, distribution and sale.

As a result of diligent studies to solve the problem, the present inventors have A) one or more selected from the group consisting of cellulosic polymer compounds, vinyl polymer compounds, polyethylene glycol and dextran, and B) amino acids. We have found that a dextran for contact lenses containing the above substances is useful for solving these problems, and have completed the present invention.

That is, the present invention is the invention listed below.
(1) An eye drop for contact lenses containing (A) one or more selected from the group consisting of a cellulosic polymer compound, a vinyl polymer compound, polyethylene glycol and dextran, and (B) amino acids.
(2) The eye drop for contact lenses according to (1), wherein the component (A) is a cellulosic polymer compound.
(3) The eye drop for contact lenses according to (2), wherein the cellulosic polymer compound is one or more selected from the group consisting of hydroxyethyl cellulose, hirodoxypropyl methylcellulose, and salts thereof.
(4) The eye drop for contact lenses according to any one of (1) to (3), which contains the component (A) in a proportion of 0.0001 to 25 (w / v)%.
(5) Any one of (1) to (4), wherein the component (B) is at least one selected from the group consisting of aspartic acid, aminoethyl sulfonic acid, epsilon aminocaproic acid, hyaluronic acid and salts thereof. Wearing ophthalmic solution for contact lenses described in.
(6) The eye drop for contact lenses according to any one of (1) to (5), which contains the component (B) in a proportion of 0.0001 to 10 (w / v)%.
(7) The eye drop for contact lenses according to any one of (1) to (6), which further contains (C) a nonionic surfactant.
(8) The component (C) is at least one selected from the group consisting of polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oils, and polyoxyethylene polyoxypropylene copolymers, (7). Wearing ophthalmic solution for contact lenses described in.
(9) The eye drop for contact lenses according to (7), wherein the component (C) is polysorbate 80.
(10) The eye drop for contact lenses according to any one of (7) to (9), which contains the component (C) in a proportion of 0.001 to 5 (w / v)%.
(11) The contact lens wearing ophthalmic solution according to any one of (1) to (10), wherein the contact lens is a soft contact lens.
(12) The eye drop for contact lenses according to (11), wherein the soft contact lens is, in principle, a soft contact lens belonging to the soft contact lens classification group IV.
(13) The eye drop for contact lenses according to (11), wherein the soft contact lens is a soft contact lens made of a silicone hydrogel lens material.
(14) The eye drop for contact lenses according to any one of items (1) to (13), which is used for suppressing dry eyes or dry eyes.
(15) The eye drop for contact lenses according to any one of items (1) to (13), which is for improving eyestrain or contrast sensitivity.

According to the contact lens wearing ophthalmic solution of the present invention, the tear film during contact lens wearing can be efficiently stabilized, and dry eyes, tired eyes, and deterioration of contrast sensitivity can be effectively suppressed.
In addition, the eye drops worn for contact lenses of the present invention also have an effect of reducing stress on the eyes by wearing contact lenses. It is considered that stress on corneal cells is also related to dry eyes and tired eyes when wearing contact lenses, and the effect of improving the dry eyes and tired eyes by the contact lens wearing ophthalmic solution of the present invention is the stress caused by wearing contact lenses. It is thought to be accompanied by mitigation.
Moreover, the contact lens wearing ophthalmic solution of the present invention has a good usability, and it is not necessary to prepare the contact lens wearing solution and the ophthalmic solution separately as in the conventional case, so that it is excellent in convenience and portability, and there is a risk of misuse. Highly safe.
Furthermore, it has advantages such as cost reduction at the manufacturing stage, reduction of transportation cost at the distribution stage, efficiency of transportation and display, and improvement of safety of product handling at the sales stage. Therefore, the eye drops worn for contact lenses of the present invention contribute to reduction of energy consumption, are useful for energy saving, and also have an effect of reducing adverse effects on the environment.
As described above, according to the present invention, it is highly effective in suppressing dryness of eyes while wearing contact lenses, improving tired eyes, and improving contrast sensitivity, and is highly safe and convenient. In addition, wearing eye drops that enable safety and efficiency at all stages from manufacturing to sales are provided, improving the convenience and safety of contact lens users, and leading to manufacturing, transportation, and sales. It is possible to achieve efficiency improvement at each stage at the same time.

Hereinafter, the present invention will be described in detail.
In the present specification, the notation "wearing" represents the act (operation) of "wearing" the contact lens, and the notation "wearing" represents the state in which the contact lens is "on the cornea".
Further, in the present specification, the notation "%" means w / v%, that is, the weight g of each component (solute) dissolved in 100 mL of the solution, unless otherwise specified.

Further, in the present specification, the "contact lens wearing ophthalmic solution" refers to an ophthalmic composition having both a function as a contact lens wearing solution and a function as an ophthalmic solution that can be instilled while wearing a contact lens. means. Further, the wearing ophthalmic solution of the present invention is an ophthalmic composition that can be used as a wearing solution for the same composition when wearing a contact lens and then as an eye drop for the eye on which the contact lens is worn. be. In the present specification, "wearing eye drops for contact lenses" may be simply referred to as "wearing eye drops".

Further, the term "contact lens" is used to include all types of contact lenses such as hard, oxygen permeable hard, and soft, unless otherwise specified. Hereinafter, "contact lens" may be simply referred to as "lens".
In addition, in this specification, "soft contact lenses" means "for soft contact lenses and soft contact lenses", which was notified by the Director of the Examination and Management Division, Pharmaceutical Safety Bureau, Ministry of Health, Labor and Welfare (Ministry of Health, Labor and Welfare at that time) dated March 31, 1999. This is the classification of SCL based on "Classification method of soft contact lenses" specified in "Handling of materials to be attached when applying for approval of manufacturing (import) of disinfectants". Here, soft contact lenses are classified based on the water content, the molar% of the monomer having an anion, and the like. For example, SCL belonging to Group IV has a common property that the water content is 50% or more and the molar% of the monomer having an anion among the constituent monomers of the raw material polymer is 1% or more. This classification follows the FDA (US Food and Drug Administration) classification method for soft contact lenses. In addition, "in principle" means to include soft contact lenses that can be understood by those skilled in the art as equivalent to those belonging to the classification in terms of materials, functions, and the like.

In addition, a contact lens made of a silicone hydrogel material is a material containing silicone (for example, TRIS or a TRIS derivative which is a polymer of silicone and acrylate) and a hydrophilic monomer (for example, hydrokiesiethyl methacrylate, dimethylacrylamide, etc.). It is a contact lens using a polymerized material, and examples of the material name based on USAN (United State Adopted Name) include LotrafilconA, LotrafilconB, BalafilconA, GalyfilconA, and SenofilconA.

The eye drops worn for contact lenses in the present invention contain (A) one or more selected from the group consisting of cellulosic polymer compounds, vinyl polymer compounds, polyethylene glycol and dextran, and (B) amino acids. It is characterized by. By containing these components, it is possible to stabilize the tear film while wearing contact lenses and, by extension, suppress dry eyes, which is effective in improving eyestrain and contrast sensitivity, and at the same time, a feeling of use. Can be improved. Further, by using the same formulation of the present invention as a contact lens wearing solution and an ophthalmic solution, different liquid drug solutions do not coexist on the cornea and conjunctiva via the contact lens, and the mechanism has been elucidated in detail. However, the effect of the interaction between the drug solution and contact lenses on the eyes and tears is probably minimized, and as a result, the tear layer is kept stable, and it is effective in improving tired eyes and contrast sensitivity. It is considered to have the above-mentioned effects such as exerting and having a good usability.

The wearing ophthalmic solution for contact lenses of the present invention is one or more selected from the group consisting of cellulosic polymer compounds, vinyl polymer compounds, polyethylene glycol and dextran (hereinafter, may be simply referred to as component (A)). There is).
The cellulosic polymer compound is a cellulosic polymer compound obtained by replacing the hydroxyl group of cellulose with another functional group, which can impart viscosity to the aqueous composition and is applicable to contact lenses. Possible compounds can be used. Examples of the functional group that replaces the hydroxyl group of cellulose include a methoxy group, an ethoxy group, a hydroxymethoxy group, a hydroxyethoxy group, a hydroxypropoxy group, a carboxymethoxy group, and a carboxyethoxy group. Examples of cellulosic polymer compounds include methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, and salts thereof. Here, as the salt, a pharmacologically acceptable salt is preferable, an alkali metal salt is more preferable, and a sodium salt, a potassium salt and the like are particularly preferable. The cellulosic polymer compound used in the present invention is not limited in the degree of substitution of the substituent and the molecular weight, but for example, the weight average molecular weight is 5,000 to 1,000,000, preferably 10,000 to 500,000, and more preferably 10,000. About 100,000 can be used. Further, as these cellulosic polymer compounds, commercially available ones can be used, and one kind or a combination of two or more kinds of these compounds may be used. Among them, from the viewpoint of further enhancing the effect of the present invention, it is preferably one or more selected from the group consisting of methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, and salts thereof. More preferably, it is hydroxypropylmethyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, and particularly preferably hydroxypropyl methyl cellulose or hydroxyethyl cellulose.

The content of the cellulosic polymer compound in the contact lens wearing ophthalmic solution in the present invention is not limited because it varies depending on the type and molecular weight of the compound, but these are based on the total amount of the contact lens wearing ophthalmic solution. The total amount of the compound is usually 0.0001 to 25%, preferably 0.001 to 10%, more preferably 0.001 to 7%, still more preferably 0.005 to 5%, and particularly preferably 0.01 to. It is 1%.

As the vinyl-based polymer compound, a compound that can impart viscosity to the aqueous composition and is applicable to contact lenses can be used. Examples of vinyl-based polymer compounds include vinyl alcohol-based polymers such as polyvinyl alcohol (completely or partially saponified product), vinylpyrrolidone-based polymers such as polyvinylpyrrolidone, and carboxyvinyl polymers. The vinyl-based polymer compound used in the present invention has no limitation on its molecular weight, but is, for example, one having a weight average molecular weight of 5,000 to 1,000,000, preferably 10,000 to 500,000, and more preferably 10,000 to 400,000. Can be used. Further, as these vinyl-based polymer compounds, commercially available ones can be used, and one kind or a combination of two or more kinds of these compounds may be used. Among them, from the viewpoint of further enhancing the effect of the present invention, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, polyvinyl alcohol (partially saponified product), and carboxyvinyl polymer are preferable, and polyvinyl alcohol (partial) is more preferable. It is a saponified product), a carboxyvinyl polymer, and particularly preferably polyvinyl alcohol (partially saponified product).

The content of the vinyl-based polymer compound in the contact lens wearing ophthalmic solution in the present invention is not limited because it varies depending on the type and molecular weight of the compound, but these are based on the total amount of the contact lens wearing ophthalmic solution. The total amount of the compound is usually 0.001 to 25%, preferably 0.001 to 10%, more preferably 0.005 to 5%, still more preferably 0.01 to 5%, particularly preferably 0.1 to 1. It is 3%.

Dextran is a water-soluble polymer compound obtained by partially hydrolyzing a polysaccharide produced by a certain lactic acid bacterium using sucrose as a raw material. As the dextran, a dextran having a weight average molecular weight of 5,000 to 1,000,000, preferably 10,000 to 500,000, and more preferably 10,000 to 100,000 can be used. Further, as these dextran, commercially available ones can be used, and one kind or a combination of two or more kinds can be used. Among them, dextran, dextran 70, dextran 40, and particularly preferably dextran 70 are preferable from the viewpoint of further enhancing the effect of the present invention.

The content of dextran in the contact lens wearing ophthalmic solution in the present invention is usually 0.001 to 25%, preferably 0.001 to 10%, based on the total amount of the contact lens wearing ophthalmic solution. It is preferably 0.01 to 10%, more preferably 0.01 to 5%, particularly preferably 0.01 to 1%, and even more preferably 0.01 to 0.1%.

Polyethylene glycol, also known as macrogol, has no limitation on the degree of substitution or molecular weight of the substituent, but has a weight average molecular weight of 100 to 50,000, preferably 400 to 20,000, and more preferably about 2000 to 10,000. Can be used. Further, as these polyethylene glycols, commercially available ones can be used, and one kind or a combination of two or more kinds can be used. Among them, from the viewpoint of further enhancing the effect of the present invention, macrogol 6000, macrogol 4000, and macrogol 400 are preferable, and macrogol 6000 and macrogol 4000 are particularly preferable.

The content of polyethylene glycol in the contact lens wearing ophthalmic solution in the present invention is usually 0.001 to 25%, preferably 0.001 to 10%, based on the total amount of the contact lens wearing ophthalmic solution. It is more preferably 0.01 to 10%, still more preferably 0.05 to 5%, and particularly preferably 0.05 to 2%.

The component (A) in the present invention may be used alone or in combination of two or more. From the viewpoint of further enhancing the effect of the present invention, the preferable component (A) is a cellulosic polymer compound, and among them, hydroxypropylmethyl cellulose and hydroxyethyl cellulose are particularly preferable.
The content of the component (A) in the contact lens wearing ophthalmic solution in the present invention is usually 0.0001 to 25%, preferably 0.001 to 10%, based on the total amount of the contact lens wearing ophthalmic solution. %, More preferably 0.005 to 10%, still more preferably 0.01 to 7%, and particularly preferably 0.01 to 5%.

The eye drops worn for contact lenses of the present invention further contain amino acids (hereinafter, may be simply referred to as component (B)).
The amino acids used in the present invention mean a compound or a derivative thereof which includes an amino acid or a salt thereof and an amino acid analog and has an amino group and a carboxyl group or a sulfone group in the molecule.

Amino acids include, for example, monoaminomonocarboxylic acids such as glycine, alanine, aminobutyric acid, aminovaleric acid, aminocaproic acid; monoaminodicarboxylic acids such as aspartic acid and glutamic acid or salts thereof; diaminomonocarboxylic acids such as arginine and lysine. Acids or salts thereof; aminoethylsulfonic acid (taurine) or salts thereof; hyaluronic acid or salts thereof and the like. Specific examples include glycine, alanine, γ-aminobutyric acid, γ-aminovaleric acid, epsilon aminocaproic acid, aspartic acid, glutamic acid, arginine, aminoethylsulfonic acid, hyaluronic acid or salts thereof. Amino acid salts include pharmaceutically, pharmacologically or physiologically acceptable salts. Such salts include salts with organic acids [eg, monocarboxylates (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylates (fumarate). , Maleate, etc.), Oxycarboxylic acid salt (lactate, tartrate, citrate, succinate, malonate, etc.), Organic sulfonate (methanesulfonate, toluenesulfonate, tosylate, etc.) Etc.], salts with inorganic acids (eg, hydrochlorides, sulfates, nitrates, hydrobromates, phosphates, etc.), salts with organic bases (eg, methylamine, triethylamine, triethanolamine, etc.), Salts with organic amines such as morpholin, piperazine, pyrrolidine, tripyridine, picolin), salts with inorganic bases [eg ammonium salts; alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), Salts with metals such as aluminum] and the like can be exemplified, and are appropriately selected depending on the compound. For example, in the case of a monoaminodicarboxylic acid, a salt with an inorganic base is preferable, and an alkali metal salt or an alkaline earth metal salt is particularly preferable.

Preferred amino acids are glycine, alanine, γ-aminobutyric acid, γ-aminovaleric acid, epsilon aminocaproic acid, sodium aspartate, potassium aspartate, magnesium aspartate, calcium aspartate, magnesium-potassium L-aspartate (equal amounts). Mixture), glutamic acid, glutamic acid hydrochloride, magnesium glutamate, aminoethylsulfonic acid, hyaluronic acid, sodium hyaluronate and the like. More preferably, it is epsilon aminocaproic acid, potassium aspartate, magnesium aspartate, magnesium-potassium L-aspartate (equal mixture), aminoethylsulfonic acid, sodium hyaluronate. The amino acids of the present invention may be D-form, L-form, or DL-form. In addition, the amino acids of the present invention can be used alone or in combination of two or more.

The content of amino acids in the contact lens mounting solution in the present invention is not limited because it varies depending on the type and molecular weight of the compound, but is usually the total amount of these compounds relative to the total amount of the contact lens mounting solution. It is 0.0001 to 10%, preferably 0.001 to 10%, more preferably 0.005 to 8%, still more preferably 0.02 to 5% by weight, particularly preferably 0.02 to 3% by weight, still more preferably 0.05 to 2%.

Further, the contact lens wearing ophthalmic solution of the present invention may contain an appropriate nonionic surfactant (hereinafter, may be simply referred to as component (C)), if necessary.
As the nonionic surfactant used in the present invention, those which can be usually used for ophthalmic compositions for contact lenses by those skilled in the art can be used, and polyoxyethylene-poly such as poloxamer 407, poloxamer 235, and poloxamer 188, for example. Oxypropylene block copolymer (hereinafter also referred to as polyoxyethylene polyoxypropylene copolymer); POE-POP block copolymer adduct of ethylenediamine such as poloxamer; POE (20) monolaurylate (polysorbate 20), monooleic acid POE sorbitan fatty acid esters such as POE (20) sorbitan (polysolvate 80), POE sorbitan monostearate (polysolvate 60), POE sorbitan tristearate (polysolvate 65); POE hardened poloxamer oil 5, POE poloxamer oil 10, POE POE-cured poloxamers such as 20, POE-cured poloxamer oil 40, POE-cured poloxamer oil 50, POE-cured poloxamer oil 60, POE-cured poloxamer oil 100; POE (9) POE alkyl ethers such as lauryl ether; POE (20) POE / POP alkyl ethers such as POP (4) cetyl ether; POE alkylphenyl ethers such as POE (10) nonylphenyl ether and the like can be mentioned. In addition, POE indicates polyoxyethylene, POP indicates polyoxypropylene, and the numbers in parentheses indicate the number of added moles.
Of these, polyoxyethylene-polyoxypropylene block copolymer, POE sorbitan fatty acid esters or POE-hardened castor oils are preferable, and poloxamer 407, polysorbate 80, and POE-hardened castor oil 60 are particularly preferable.

The content of the nonionic surfactant in the contact lens wearing ophthalmic solution in the present invention cannot be unconditionally specified because it differs depending on the type of the surfactant and the like, but these are relative to the total amount of the contact lens wearing ophthalmic solution. The total amount is usually 0.001 to 5%, preferably 0.001 to 1.5%, more preferably 0.001 to 1%, still more preferably 0.005 to 0.5%, and particularly preferably 0.05. ~ 0.3%.

The contact lens wearing ophthalmic solution of the present invention preferably contains an appropriate buffer, if necessary. Examples of the buffer used in the present invention include borate buffer, phosphate buffer, carbonic acid buffer, citric acid buffer, acetate buffer, HEPES buffer, MOPS buffer and the like. More specifically, boric acid, sodium borate, potassium tetraborate, boric acid, potassium metaborate, phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, carbonic acid, sodium hydrogen carbonate, Examples thereof include compounds such as sodium carbonate, boric acid, sodium citrate, potassium citrate, acetic acid, sodium acetate, HEPES, and MOPS, hydrates thereof, and combinations of two or more compounds selected from these groups.

Preferred buffers are boric acid buffers, phosphate buffers, carbonate buffers and citrate buffers. Particularly preferred buffers are boric acid buffers or phosphate buffers. Particularly preferable buffers are, more specifically, borates such as borate, alkali metal borate, alkaline earth metal borate, and combinations of borate and borate as borate buffers. Borate and borate are particularly preferable, and examples of the phosphate buffer include phosphates such as phosphoric acid, alkali metal phosphate, alkaline earth metal phosphate, hydrates thereof, and phosphoric acid. A combination with a phosphate can be mentioned, and sodium hydrogen phosphate, sodium dihydrogen phosphate, and hydrates thereof are particularly preferable.

The content of the buffering agent in the contact lens wearing ophthalmic solution in the present invention cannot be unconditionally specified because it differs depending on the type of the buffering agent and the like, but these are the total amount, which is usually 0, based on the total amount of the contact lens wearing ophthalmic solution. .001 to 5%, preferably 0.001 to 3%, more preferably 0.005 to 2.0%, still more preferably 0.005 to 1.5%, particularly preferably 0.05 to 1.5%. Is.

It is preferable to add an appropriate inorganic salt to the contact lens wearing ophthalmic solution of the present invention, if necessary. Examples of the inorganic salts include potassium chloride, sodium chloride, sodium hydrogen carbonate, and sodium carbonate, and one or a combination of two or more of these may be used.
The content of inorganic salts in the contact lens wearing ophthalmic solution in the present invention cannot be unconditionally specified because it differs depending on the type of inorganic salts and the like, but these are the total amount, which is usually 0, based on the total amount of the contact lens wearing ophthalmic solution. It is used at .001-5%, preferably 0.01-1.5%, more preferably 0.1-0.7%.

It is preferable to add an appropriate ethylenediamineacetic acid derivative or a salt thereof to the contact lens mounting solution of the present invention, if necessary. Examples of the ethylenediamineacetic acid derivative or a salt thereof include edetic acid (ethylenediaminetetraacetic acid, EDTA), ethylenediaminediacetic acid (EDDA), diethylenetriaminepentaacetic acid (DTPA), and N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA). Alternatively, their salts and the like can be exemplified. The salt of the ethylenediamine acetic acid derivative includes a pharmacologically or physiologically acceptable salt, and examples thereof include a salt with an alkali metal (sodium, potassium, etc.), a salt with an alkaline earth metal (calcium, etc.), and the like. .. Of these, ethylenediaminetetraacetic acid or a salt thereof is preferable, and for example, ethylenediaminetetraacetic acid disodium, ethylenediaminetetraacetic acid disodium, ethylenediaminetetraacetic acid disodium / dihydrate (hereinafter, also referred to as sodium edetate). , Particularly preferably ethylenediaminetetraacetic acid disodium / dihydrate. These can be used alone or in combination of two or more.

The content of the ethylenediamine acetic acid derivative or its salt in the eye drops for contact lenses in the present invention cannot be unconditionally specified because it varies depending on the molecular weight and type, but these are the total amount with respect to the total amount of the eye drops for contact lenses. It is preferably 0.0001 to 1%, more preferably 0.0005 to 0.5%, still more preferably 0.001 to 0.3%, and particularly preferably 0.001 to 0.05%.

Further, in order to further exert the effect of the present invention, it is more preferable to blend an ethylenediamineacetic acid derivative or a salt thereof, a nonionic surfactant, an inorganic salt and a buffer in combination.
The content of the ethylenediamine acetic acid derivative or its salt, nonionic surfactant, inorganic salts, and buffer in the contact lens eye drops in the present invention is the total amount of these relative to the total amount of the contact lens eye drops. , 0.01 to 5%, and particularly preferably 0.05 to 3%.

The contact lens wearing ophthalmic solution of the present invention is particularly preferably used for soft contact lenses among contact lenses. This is because soft contact lenses are said to be easy to feel dry and to put a strain on the eyes. Of these, it is particularly preferable because it is useful for highly water-containing soft contact lenses that tend to feel dry, and in particular, soft contact lenses of the soft contact lens classification group IV. In addition, surprisingly, a soft contact lens made of a silicone hydrogel material exerts a remarkable effect of the invention, and therefore its use in the soft contact lens is also preferable.

The eye drops worn for contact lenses of the present invention are suitable for containing various components (including pharmacologically active ingredients and physiologically active ingredients) in combination. Decongestant components, eye muscle regulator components, anti-inflammatory drug components or astringent drug components, antihistamine drug components or antiallergic drug components, vitamins, acidic mucopolysaccharides, local anesthetic components, etc., which are usually used in ophthalmic compositions. It can be illustrated. Specifically, the following components can be exemplified.

Congestion-removing ingredients: eg, α-adrenaline agonists, specifically epinephrine, ephedrine hydrochloride, ephedrine hydrochloride, oxymethazoline hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, phenyleffrin hydrochloride, methylephedrine hydrochloride, ephedrine hydrogen tartrate, naphazoline nitrate and the like. These may be d-form, l-form or dl-form.
Eye muscle regulator components: For example, cholinesterase inhibitors having an active center similar to acetylcholine, specifically neostigmine methylsulfate, tropicamide, atropine heleniensulfate, and the like.

Anti-inflammatory or astringent ingredients: eg zinc sulphate, zinc lactate, allantin, epsilon-aminocaproic acid, indomethacin, lysozyme chloride, silver nitrate, pranoprofen, sodium azulenate, dipotassium glycyrrhizinate, diclofenac sodium, bromfenac Zinc sodium, velverin chloride, velverin sulfate, etc.

Antihistamine or antiallergic ingredients: for example, acitazanolast, amlexanox, ibudilast, tranilast, diphenhydramine hydrochloride, levocabastine hydrochloride, ketotifen fumarate, sodium cromoglycate, pemirolast potassium, chlorpheniramine maleate, etc.

Vitamins: For example, retinyl acetate, retinol palmitate, pyridoxine hydrochloride, flavin adenine dinucleotide sodium, pyridoxal phosphate, cyanocobalamin, panthenol, calcium pantothenate, sodium pantothenate, ascorbic acid, tocopherol acetate and the like.

Acidic mucopolysaccharides: for example, sodium chondroitin sulfate.

Local anesthetic ingredients: for example, chlorobutanol, oxybuprocaine hydrochloride, cocaine hydrochloride, cornecaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, parabutylaminobenzoic acid diethylaminoethyl hydrochloride, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothiocaine hydrochloride, hydrochloric acid. Lidocaine etc.

In addition, for the contact lens wearing ophthalmic solution of the present invention, various components and additives are appropriately selected according to a conventional method according to the use and form within the range not impairing the effect of the invention, and one or more thereof are used. It may be contained. As their components or additives, for example, carriers (such as water, aqueous solvents, aqueous or oily bases) commonly used in the preparation of semi-solids, liquids and the like, thickeners, sugars, sugar alcohols, etc. Examples include various additives such as acidic mucopolysaccharides, surfactants, preservatives, bactericides or antibacterial agents, pH regulators, isotonic agents, fragrances or cooling agents, stabilizers and the like.

The following are examples of typical components used in the contact lens wearing eye drops of the present invention, but the present invention is not limited thereto.
Sugars: For example, glucose, cyclodextrin, etc.
Sugar alcohols: For example, xylitol, sorbitol, mannitol, etc.
Acidic mucopolysaccharides: alginic acid, sodium alginate, etc.
Surfactant: For example, in addition to the nonionic surfactant described above, a glycine-type amphoteric surfactant such as alkyldiaminoethylglycine; alkyl quaternary ammonium salt (specifically, benzalkonium chloride, benzethonium chloride, etc.) Benzalkonium surfactant etc.) etc.

Preservatives, disinfectants 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, biganide compounds (specifically, polyhexamethylene biguanide or its hydrochlorides, etc.), polydronium chloride , Glokill (trade name made by Rhodia), 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.
Isotonic agents: for example, sodium hydrogen sulfite, sodium sulfite, magnesium chloride, potassium acetate, sodium acetate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol and the like.

Stabilizers: dibutylhydroxytoluene, tromethamole, sodium formaldehyde sulfoxylate (longalit), tocopherol, sodium metabisulfite, monoethanolamine, aluminum monostearate, etc.
Fragrances or refreshing agents: terpenes (eg, anethole, eugenol, camphor, geraniol, cineole, borneol, menthol, limonene, ryuno, etc. These may be d, l or dl), essential oils (uikyo) Oil, cool mint oil, kehi oil, spear mint oil, camphor water, camphor oil, peppermint oil, bergamot oil, eucalyptus oil, rose oil, etc.).

The contact lens wearing ophthalmic solution of the present invention can be initially set to an appropriate viscosity in order to obtain a desired effect, and the set viscosity can be stably maintained for a long period of time. When setting the viscosity of an ophthalmic composition for contact lenses, it is preferable to keep the viscosity at 20 ° C. at 1.1 mPa · s or more, and it is usually 1.1 to 300 mPa · s, preferably 1.3. It can be designed to be ~ 100 mPa · s, particularly preferably 1.5 to 80 mPa · s.

Viscosity is measured by using a conical plate type rotational viscometer (general test method described in the 14th revised Japanese Pharmacopoeia, 45. Viscosity measurement method, 2nd rotational viscometer method, "(3) Conical viscometer". -In accordance with the method described in the section "Plate-type rotational viscometer"), specifically, measurement can be performed using a commercially available conical-plate-type rotational viscometer and an appropriately selected rotor. For example, using a commercially available E-type viscometer [manufactured by TOKIMEC, sold by Toki Sangyo (Japan)] and a rotor appropriately selected, petroleum-based carbonization specified by JIS Z8809 for each measurement of the sample to be exhibited. By adjusting hydrogen oil (Newtonian fluid) as a calibration standard solution, the viscosity at 20 ° C. can be measured. Specifically, the viscosity measuring method described in JP-A-2006-348055 is followed (measurement conditions will be described later).

The contact lens wearing ophthalmic solution of the present invention is used after adjusting the osmotic pressure within the range acceptable to the living body, if necessary. The osmotic pressure is usually 0.3 to 4.1, preferably 0.4 to 4.1, more preferably 0.3 to 2.1, and particularly preferably 0.5 to the osmotic pressure ratio to the physiological saline solution. It is 1.4. For the measurement method of the osmotic pressure ratio, refer to the 15th revised Japanese Pharmacopoeia General Test Method Osmotic Pressure Measurement Method.

The contact lens wearing ophthalmic solution of the present invention is used after adjusting the pH to a pH within a range applicable to a living body, if necessary. The pH is usually pH 4.0 to 9.0, preferably 5.0 to 8.5, and particularly preferably 5.5 to 8.5. The pH can be adjusted by using the buffer, the pH adjuster, or the like.

The contact lens wearing ophthalmic solution of the present invention can be produced by a known method, and if necessary, a filtration sterilization step, a container filling step, and the like can be added.

As a method of using the contact lens wearing ophthalmic solution of the present invention, "when wearing the contact lens (immediately before wearing), the contact lens wearing ophthalmic solution is dropped directly onto the contact lens, and an appropriate amount of both sides or one side of the contact lens ( For example, preferably after wetting with 1 to 2 drops at a time), the contact lens is attached and used ”(the inside of the above-mentioned brackets may be hereinafter referred to as“ contact lens attachment liquid use ”). There is a way to do it. Further, "use an appropriate amount (for example, preferably 1 to 2 drops at a time) of eye drops worn for contact lenses while wearing contact lenses" (the above-mentioned brackets are hereinafter referred to as "use as eye drops". There is a method to describe). The number of instillations per day is not limited, but is usually in the range of 1 to 10 times, preferably 1 to 6 times, and particularly preferably 5 to 6 times.

Further, as a method of using the contact lens wearing ophthalmic solution, as described above, the interval from the contact lens wearing ophthalmic use to the first instillation after wearing the contact lens is preferably within 5 hours. It is within 2 hours, more preferably within 1 hour, further preferably within 30 minutes, particularly preferably within 10 minutes, and even more preferably within 2 minutes. Subsequent instillation is similar to the use of normal ophthalmic solution.

Furthermore, the present invention includes the following contact lens processing steps. That is, 1. A step of dripping contact lens wearing ophthalmic solution directly onto a contact lens and wetting both sides or one side of the contact lens with an appropriate amount (for example, preferably 1 to 2 drops at a time) when wearing a contact lens (immediately before wearing). 2. The process of wearing contact lenses on the eyes, 3. A process of wetting a contact lens by instilling the liquid while wearing the contact lens. Furthermore, the present invention can include the following contact lens processing steps. 4. 4. A process of wetting contact lenses by instilling the liquid when removing the contact lenses from the eyes (immediately before removing them). The process of removing contact lenses from the eyes, 6. The process of instilling contact lens eye drops immediately before wearing contact lenses. When processing contact lenses, an appropriate step may be selected from the above steps, if necessary.

From the viewpoint of more preferably exerting the effects of the present invention, the contact lens wearing ophthalmic solution of the present invention is preferably used for both contact lens wearing solution use and contact lens wearing ophthalmic solution use. Although it is intended, it can be used for only one of them.

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.
In the test example, the test was performed continuously as much as possible in order to keep the measurement conditions, especially the condition of the subject, substantially constant. Each test example was conducted independently.
The viscosities of each example and comparative example are as follows, using a TVE-20L viscometer cone plate type (manufactured by TOKIMEC, Toki Sangyo (Japan)), which is one of the E-type viscometers. The measurement was performed under the measurement conditions according to the manufacturer's instructions. Unless otherwise specified, the viscosity measuring method described in JP-A-2006-348055 is followed. However, the measurement conditions are as follows.
Measurement condition:
Rotational speed: 100 rpm (Since the allowable range of rotational speed differs depending on the viscosity, the highest rotational speed that can be measured according to each prescription is used.)
Sample volume: 1 ml
Measurement temperature: 20 ° C
Time: The viscosity after 3 minutes was taken as the measured value.

Test 1: Evaluation by dry eye observation device (DR-1, Kowa Co., Ltd.) (test method)
According to the formulation shown in Table 1, the contact lens wearing ophthalmic solutions of Examples 1 to 7 and Comparative Examples 1 to 3 were prepared according to a normal method for preparing eye drops and the like (conventional method), and a polyethylene terephthalate container (capacity: 10 mL) was prepared. ), And plugged with a nozzle and a cap. Soft contact lenses are Ciba Vision's soft contact lens classification group I (silicone hydrogel lens main material: Lotrafilcon A) (hereinafter sometimes referred to as SCL1), and Johnson &Johnson's soft contact lens classification group IV. Main material: EtafilconA (hereinafter sometimes referred to as SCL2) was used. After wetting both sides of the contact lens drop by drop with the wearing ophthalmic solution of each prescription, the contact lens was put on, and 2 minutes after the wearing, the wearing ophthalmic solution of the same prescription was instilled.
Then, the evaluation was carried out according to each test condition (1) to (3). In addition, three subjects who wear contact lenses on a daily basis and feel dryness (those who tend to have dry eye) were selected. In addition, after the test was performed on one type of test solution, the test was performed on the next test solution after the eyes were sufficiently rested.

(1) Evaluation of dry spot area-1
Under the above-mentioned conditions, the contact lens wearing ophthalmic solution was used as a contact lens wearing solution, and then the solution was instilled while wearing the contact lens, and then the area of the dry spot was evaluated under the following conditions.
A dry eye observation device (DR-1, Kowa Co., Ltd.) for observing the interference color of the tear oil layer was used for observing the dry spot. Specifically, the number and size of dry spots on the ocular surface 1 second after the start of the blink were measured for the blink about 2 minutes after the instillation. For each dry spot, the area value was calculated from the image, and the total area value was calculated as the total area for each formulation. After that, the results of the three subjects were averaged, and the relative value of the total area of each example prescription and the comparative example prescription was calculated when the total area of Example 1 was 1, and "relative of the total area of the dry spots" was calculated. The results are shown in Table 2 as "evaluation".

ドライスポットは、眼科領域ではドライアイや目の乾きを表す指標として認識されており、ドライスポットの発生時間が短い、ドライスポットの数が多い、ドライスポットの面積が大きいなどは、より目が乾いた状態にあると言える。この試験結果より、実施例処方においては、比較例処方と比較して、ドライスポットの総面積が顕著に小さかった。従って実施例処方では、コンタクトレンズ表面の涙液層が安定化され、ドライスポットが出来難かったと言える。またこの事は、目の乾燥が顕著に抑制された事を示しており、ドライアイ症状の改善を示している。

Dry spots are recognized in the ophthalmology field as indicators of dry eye and dry eyes, and the eyes are drier when the dry spots occur for a short time, the number of dry spots is large, and the area of the dry spots is large. It can be said that it is in a state of being. From this test result, the total area of the dry spots in the Example formulation was significantly smaller than that in the Comparative Example formulation. Therefore, it can be said that in the formulation of the example, the tear film on the surface of the contact lens was stabilized and it was difficult to form a dry spot. This also indicates that the dryness of the eyes was significantly suppressed, indicating an improvement in the symptoms of dry eye.

(2) Evaluation of dry spot area-2
Under the above-mentioned conditions, the contact lens wearing ophthalmic solution was used as a contact lens wearing solution, and then the solution was instilled while wearing the contact lens, and then the area of the dry spot was evaluated under the following conditions.
Using the dry eye observation device (DR-1), image analysis is performed on the area of the largest dry spot observed between the start of the blink and the start of the next blink for the blink about 11 minutes after instillation. The area ratio (%) with respect to the entire observation area on the ocular surface was determined by analysis with the device. In addition, 11 minutes after instillation, the dry spot was particularly advanced in the case of the comparative example prescription, and the dry spot was observed in the form of one cohesive dry area. Calculate the average of the total area ratio of the three subjects and the relative value of the area ratio of each prescription when the area ratio of Example 1 is 1, and the result is shown as "Evaluation of dry spot area-2". Shown in 3.

前述の通り、ドライスポットが大きいと、より眼が乾燥状態にあると言える。この試験結果より、点眼して充分時間が経過した後でさえ、実施例処方においてはドライスポットの面積の割合が小さく、コンタクトレンズ表面の涙液層が安定化されており、眼の乾燥が顕著に抑制された事を示している。また、この事はドライアイ症状の改善を示している。

As mentioned above, it can be said that the larger the dry spot, the drier the eyes. From this test result, even after a sufficient time has passed after instillation, the ratio of the area of the dry spot is small in the formulation of the example, the tear film on the surface of the contact lens is stabilized, and the dryness of the eye is remarkable. It shows that it was suppressed. This also indicates an improvement in dry eye symptoms.

(3) Evaluation of tear stability Under the above conditions, the contact lens wearing ophthalmic solution is used as a contact lens wearing solution, and then the solution is instilled while wearing the contact lens, and then the tear solution is applied under the following conditions. Stability was evaluated.
The movement of the tear oil layer from the start of the blink to the start of the next blink about 3 minutes after instillation was observed with a dry eye observation device (DR-1), and evaluation scores were given according to the criteria shown in Table 4. .. In addition, the movement of the tear oil layer before instillation was also given an evaluation score. The larger the evaluation score, the thinner or uneven the oil layer in the tear film, indicating that the tear film is in an unstable state. The difference between the evaluation scores before and after instillation was defined as the degree of improvement in tear stability, and was evaluated according to the criteria shown in Table 5. Table 7 shows the results of averaging the evaluation scores of the three subjects.

この試験結果から、実施例処方では、涙液層における油層が乱れ難く、安定しているが、比較例処方では、涙液層における油層が乱れやすく、涙液層が不安定な状態になることが分かった。前述したように涙液層における油層が薄くなると、涙液の蒸発が促進され、眼が乾燥しやすくなる事が知られている。従って、上記の結果は、実施例処方では、比較例処方と比較して、眼の乾燥が顕著に抑制された事を示している。また、この事はドライアイ症状の改善を示している。

From this test result, in the example formulation, the oil layer in the tear film is not easily disturbed and stable, but in the comparative example formulation, the oil layer in the tear film is easily disturbed and the tear film becomes unstable. I found out. As described above, it is known that when the oil layer in the tear film becomes thin, the evaporation of tear fluid is promoted and the eyes become dry easily. Therefore, the above results indicate that the dryness of the eyes was remarkably suppressed in the example formulation as compared with the comparative example formulation. This also indicates an improvement in dry eye symptoms.

Test 2: Evaluation of usability
The following evaluations were performed on 10 subjects. After wetting both sides of the contact lens drop by drop with the wearing eye drops, the contact lens was worn. After instilling the same wearing ophthalmic solution 2 minutes after wearing, a feeling of dryness, a feeling of convergence, and an unpleasant sticky feeling due to the component (A) (a feeling of stickiness. Regarding the feeling of sticking), the corresponding feeling of use was scored according to the evaluation criteria in Tables 7, 8 and 9. Table 11 shows the results of evaluating the average of the subjects according to the criteria shown in Table 10.

試験の結果、実施例処方では、自覚症状として、乾燥感、収斂感、ネバつき感が顕著に抑制されていた。

As a result of the test, in the example formulation, the feeling of dryness, the feeling of convergence, and the feeling of stickiness were remarkably suppressed as subjective symptoms.

Test 3: Confirmation of usefulness of combination by prescription According to the prescription in Table 12, for each of prescriptions 1 to 3, the eye drops, the contact lens wearing solution, and the contact lens wearing ophthalmic solution were prepared by the usual method of preparing eye drops and the like (usually). It was prepared according to the method), filled in a polyethylene terephthalate container (capacity: 10 mL), and capped with a nozzle and a cap. In addition, the test methods other than those specified were the same as in Test 1 and Test 2 described above, and a test was conducted to confirm the usefulness of the combination by prescription. Prescription 1 and Prescription 2 are prescriptions for the ophthalmic composition of the present invention. Specifically, Prescription 1, Prescription 2, and Prescription 3 are the first, fifth, and comparative examples shown in Table 1, respectively. It is the same prescription as 3. The results are shown in Table 13.

本発明の処方を装着点眼液として用いた場合、（実施試験例1、2）と、本発明とは異なる処方を装着点眼液として用いた場合（比較試験例3）では、実施試験例1、2のほうが、涙液油層の安定性が高く、ドライスポットの面積の評価においても顕著に小さく、従って眼の乾燥が顕著に抑制されていた。また収斂感、ネバつき感及び乾燥感の自覚症状においても、優れた効果が確認された。さらに、処方上は本発明の範囲内の組成物であっても、装着点眼液として装着時及び点眼時に同一の組成物を同一のコンタクトレンズ又は眼球に対して用いた場合（実施試験例1、2）と、装着時と点眼時に異なる組成物を用いた場合（比較試験例4、5）を比較すると、実施試験例1、2の方が顕著に優れた効果を示した。

When the formulation of the present invention was used as the wearing ophthalmic solution (Examples 1 and 2), and when a formulation different from the present invention was used as the wearing ophthalmic solution (Comparative Test Example 3), the implementation test example 1 and In No. 2, the stability of the tear oil layer was higher, and the area of the dry spot was also remarkably small, so that the dryness of the eyes was remarkably suppressed. In addition, an excellent effect was confirmed in the subjective symptoms of a feeling of convergence, a feeling of stickiness, and a feeling of dryness. Further, even if the composition is within the scope of the present invention in terms of formulation, when the same composition is used for the same contact lens or eyeball at the time of wearing and instilling as the wearing eye drop (Example 1, Example 1, Comparing 2) with the cases where different compositions were used at the time of wearing and instillation (Comparative Test Examples 4 and 5), the performance Test Examples 1 and 2 showed remarkably superior effects.

Test 4: Evaluation of eyestrain improvement effect (test method)
The effect of improving eyestrain was evaluated using the contact lens wearing ophthalmic solution of Formulation 1 (the same formula as in Example 1) in Table 12. The flicker value was used as an evaluation index.
Specifically, the flicker value of four subjects who wear contact lenses five days or more a week and are prone to feel tired eyes, who wear contact lenses all day for eight hours or more, and then wear contact lenses. (Flicker value before administration) was measured. The contact lenses used by the subjects were (1) Johnson & Johnson main material: SenofilconA (silicone hydrogel material), two soft contact lens classification group IV, and (2) Coopervision soft contact lenses. Classification Group I Main material: 2-Hydroxyethyl methacrylate was 1 person, (3) Oxygen permeable hard contact lens Main material: Shiroxanylstyrene was 1 person.

Next, after a sufficient period of time, remove the contact lenses of both eyes once, and drop the eye drops for contact lenses of Formulation 1 directly onto the concave surface (inside, the surface in contact with the corneum) of the contact lens, one drop per lens. Then, the contact lenses were put on both eyes again, and 15 minutes later, the contact lens wearing ophthalmic solution of Formulation 1 was instilled into both eyes one drop at a time, and the flicker value (flicker value after administration) was measured (implementation test). Example 3).
On another day, the flicker value before administration was measured by the same procedure, and one drop of the ophthalmic solution of Formulation 1 was instilled into both eyes while wearing contact lenses, and 15 minutes later, the ophthalmic solution of Formulation 1 was applied. A drop was instilled into both eyes again, and the flicker value (flicker value after administration) was measured (Comparative Test Example 6). From the measured flicker value, the flicker value improvement rate was obtained by the formula of Equation 1 described later.
Similarly, the same test was carried out using the contact lens wearing ophthalmic solution of Formulation 4 (the same formulation as Example 7) in Table 12 (Example 4 and Comparative Test Example 7).

The flicker value is a critical frequency at which the blinking cannot be discriminated by the naked eye when the blinking frequency of the blinking light is gradually increased. Using the flicker value as an index, it is possible to measure eye strain and decreased sensory function. That is, the improvement of the flicker value is an index for the improvement of eye fatigue (particularly eye fatigue caused by physical and mental fatigue accompanied by a decrease in sensory function) and eye strain.
In this test, the flicker value was measured with the following equipment and conditions.
Device name: Labor Research Institute Digital Flicker Value Measuring Instrument RDF-1 (manufactured by Sibata Scientific Technology Co., Ltd.)
Illuminance: Set to an illuminance that is easy for the measurer to see Distance: Set to a position that is easy for the measurer to see (the position where the letter "K" is most clearly visible)
SCAN knob (initial flicker frequency to lower): 60Hz
MANU-AUTO: Set to AUTO From the measured flicker value, the eye strain improvement value (flicker value improvement rate) is calculated by the following formula of Equation 1.

Table 14 shows the average of the results of the four subjects. As a result, in all of the four subjects, the flicker value improvement rate was significantly increased in the practice test example 3 as compared with the comparative test example 6. Further, in the carried-out test example 4, a remarkable increase in the flicker value improvement rate was observed as compared with the comparative test example 7. In the industry, it is generally considered that the presence or absence of an effect (clear change) is determined based on the improvement rate of the flicker value of about 3%. From the above results, the contact lens wearing ophthalmic solution of the present invention has an effect of improving tired eyes, an effect of improving eye strain, or physical and mental, as compared with the case where the eye drops are used only for eye drops like the conventional eye drops. It was confirmed that the effect of improving fatigue was remarkably excellent and the usefulness was high.

Test 5: Evaluation of contrast sensitivity improvement effect (test method)
The effect of improving the contrast sensitivity was evaluated using the contact lens wearing eye drops of Examples 1 to 7 in Table 1.
Specifically, eight subjects wearing contact lenses 5 days or more a week were contrasted using the Vision Contrast Test System (VCTS®) chart test while wearing contact lenses. Sensitivity was measured (blank). For the detailed evaluation method, refer to the instruction manual (VCTS Chart Examination Procedure, Vistech Consultants, Inc.) attached to the VCTS chart examination. The contrast sensitivity value was calculated from the Contrast Sensitivity Value Key table in the same manual. The evaluation points are A (1.5cpd), B (3cpd), C (6cpd), D (12cpd), and E (18cpd).
First, the contact lens wearing ophthalmic solution of Formulation 1 (= Example 1) in Table 12 was used as a contact lens wearing solution, and two minutes later, the same solution was instilled while wearing the contact lens. After minutes, the contrast sensitivity was measured (Example 5). The contact lenses used by the subjects were 4 for SCL1 and 4 for SCL2.

The average of the results of 8 subjects is shown in FIG. As a result, in all eight subjects, in Example 5 in which Formulation 1 was used as a contact lens wearing eye drop, the contrast sensitivity was significantly improved as compared with the blank.

上記の結果から明らかなように、実施例2〜7のコンタクトレンズ用装着点眼液を用いた場合も、実施例1と同様に、ブランクと比較してコントラスト感度が顕著に改善されていた。 Similarly, for the contact lens-worn eye drops of Examples 2 to 7, the contrast sensitivity values were measured at the point B (3cpd) where the difference was the largest, and the average of the results is shown in Table 15. The contact lenses used by the subjects were 10 for SCL1 and 10 for SCL2.

As is clear from the above results, even when the contact lens wearing eye drops of Examples 2 to 7 were used, the contrast sensitivity was remarkably improved as compared with the blank as in Example 1.

Prescription example 1-11
Wearing eye drops for contact lenses (Prescription Example 1-15) were prepared according to the formulations shown in Table 16. In Table 16, the unit of each compounding ingredient is g / 100 mL.

It is a graph which shows the improvement effect of the wearing ophthalmic solution for a contact lens of this invention with respect to the decrease of contrast sensitivity while wearing a contact lens.

Claims (1)

An eye drop for contact lenses containing (A) one or more selected from the group consisting of a cellulosic polymer compound, a vinyl polymer compound, polyethylene glycol and dextran, and (B) amino acids.

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