JP5797720B2 - Ophthalmic composition - Google Patents

Description

  The present invention relates to an ophthalmic composition for reducing the effect of a contact lens on the eye, and more specifically, the tear film, particularly an oil layer, can be stabilized and dryness can be suppressed when the contact lens is worn, and the visual function is lowered. It is related with the ophthalmic solution for contact lenses excellent in prevention of contact.

In recent years, contact lenses, especially soft contact lenses (hereinafter sometimes referred to as SCL), have been remarkably widespread for the purposes of vision correction and beauty. However, wearing contact lenses imposes a burden on the eyes, although there are individual differences.
A typical complaint of contact lens wearers is dry eyes. A healthy tear film is a thin layer having a thickness of about 7 μm and has a three-layer structure of a mucus layer, an aqueous layer, and an oil layer from the eyeball side, and protects the cornea from drying and external stimuli. In particular, the oil layer closest to the outside world prevents evaporation of tears. However, the oil layer becomes thin or uneven and unstable easily due to the thin and unstable tear layer. Liquid evaporation is promoted and dry eye symptoms such as dry eyes occur. Incidentally, due to such destruction (instability) of the tear film, spots where the oil layer is extremely thin or absent are formed in spots, and a portion called a dry spot is observed on the surface of the tear film. The dry spot is one of the important indicators of dry eye and dry eye diagnostic criteria, such as the time when the spot occurs is used to calculate tear film breakup time (BUT). Patent Document 1). In other words, if it is possible to delay the generation time of dry spots or to reduce the number and area of dry spots when the opening time is the same, it is possible to suppress dry eye symptoms such as dry eyes and tired eyes. It is thought that it is connected and has an important meaning.

Further, it is known that even when the eye is normal when it is a normal eye, when the contact lens is worn, the tear film becomes non-uniform, and it is easy to feel dryness of the eyes and dry eyes. Especially when wearing SCL, the tear film on SCL tends to be very thin, and on SCL, the oil layer is often very thin or, in some cases, a phenomenon in which the oil layer is partially or totally absent is observed. The As a result, evaporation of tear fluid is accelerated, and further, moisture in the SCL, and even moisture under the SCL, is increased, which may cause “dry eyes” and corneal damage (non-patent literature). 2).
Therefore, in order to ensure the safety of the eyes of the contact lens wearer, it is necessary to stabilize the tear film, particularly the oil layer, on the outer surface of the lens continuously and effectively.

  Conventionally, methods such as instilling artificial tears have been used to dry the eyes, but the method of simply instilling artificial tears cannot achieve stabilization of the tear film 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 an ophthalmic solution and a mounting solution for the contact lens used therefor are provided. It has been proposed (Patent Document 1). An ophthalmic liquid 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 exhibited a sufficiently long and efficient stabilizing effect of the tear film, particularly the oil layer.

  Another problem associated with wearing contact lenses is a reduction 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 reduced, for example, it may be difficult to recognize the contrast between the road surface and the obstacle when walking, leading to an accident, or in sports (especially ball games), it may be difficult to recognize the contrast between the ball and the background, which may cause inconvenience. . As a cause of a decrease in contrast sensitivity, conventionally, eyewear such as corneal refraction surgery using an excimer laser, aging, and wearing of contact lenses have been known. It has been reported that the decrease in contrast sensitivity due to contact lens wear is related to bilateral contact lenses, long-time soft contact lens wear, and continuous wear soft contact lens wear. However, as a solution to such a problem, there is an attempt to change the contact lens itself, but there is no known improvement in contrast sensitivity by the ophthalmic composition.

  By the way, ophthalmic solutions such as eye drops, eye washes, and contact lens mounting solutions basically have different purposes of use and are handled individually in use. Therefore, the user of the contact lens needs to hold the contact lens mounting solution and the eye drops separately and use them separately. However, these liquid preparations are often similar in appearance due to doses and the like, although there are different usage purposes (uses), and there is a risk of misuse. Also for the seller, there was a risk of misuse of the consumer due to misidentification at the time of guidance or mix-up of products. Therefore, the development of products that can be used easily and safely without misuse has been widely demanded 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 A JP 2007-77053 A

As described above, conventionally, ophthalmic solutions such as eye drops and contact lens mounting liquids have been handled individually. The individual performance of these preparations has been studied, but the reality is that the suitability of the combination of eye drops and contact lens mounting liquids has not been fully studied. Surprisingly, the present inventors, after wearing a contact lens using a conventional contact lens mounting solution, when instilling another prescription ophthalmic solution, sufficient tear film stabilization effect, fatigue eye improvement It has been found that not only the effect and the contrast sensitivity improving effect are not seen, but also an unpleasant feeling of use such as a feeling of stickiness or a feeling of stickiness may be generated.
Therefore, the present invention provides an ophthalmic composition that stabilizes the tear film while wearing contact lenses, suppresses dryness of the eyes, eliminates fatigued eyes and decreases in contrast sensitivity, and has a good usability. It is intended to do.
Another object of the present invention is to provide an ophthalmic composition that is excellent in convenience, free from misuse, and highly safe.
Furthermore, an object of the present invention is to provide an ophthalmic composition having high efficiency and safety at every stage from production, distribution and sales.

  As a result of intensive studies for solving the problems, the present inventors have found that A) one or more selected from the group consisting of a cellulose-based polymer compound, a vinyl-based polymer compound, polyethylene glycol and dextran, and B) amino acids. The present inventors have found that an ophthalmic solution for contact lenses containing the above is useful for solving these problems, and has completed the present invention.

That is, this invention is the invention hung up below.
(1) An ophthalmic solution for contact lenses containing (A) one or more selected from the group consisting of a cellulose-based polymer compound, a vinyl-based polymer compound, polyethylene glycol and dextran, and (B) an amino acid.
(2) The ophthalmic solution for contact lenses according to (1), wherein the component (A) is a cellulose polymer compound.
(3) The ophthalmic solution for contact lenses according to (2), wherein the cellulosic polymer compound is at least one selected from the group consisting of hydroxyethylcellulose, hydroxypropylmethylcellulose, and salts thereof.
(4) The ophthalmic solution for contact lens according to any one of (1) to (3), which contains the component (A) at a ratio of 0.0001 to 25 (w / v)%.
(5) Any of (1) to (4), wherein the component (B) is at least one selected from the group consisting of aspartic acid, aminoethylsulfonic acid, epsilon aminocaproic acid, hyaluronic acid and salts thereof. Wearing eye drops for contact lenses as described in 1.
(6) The ophthalmic solution for contact lens according to any one of (1) to (5), which contains the component (B) at a ratio of 0.0001 to 10 (w / v)%.
(7) The ophthalmic solution for contact lens according to any one of (1) to (6), further comprising (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 eye drops for contact lenses as described in 1.
(9) The ophthalmic solution for contact lenses according to (7), wherein the component (C) is polysorbate 80.
(10) The ophthalmic solution for contact lens according to any one of (7) to (9), comprising the component (C) at a ratio of 0.001 to 5 (w / v)%.
(11) The contact lens ophthalmic solution according to any one of (1) to (10), wherein the contact lens is a soft contact lens.
(12) The ophthalmic solution for contact lens according to (11), wherein the soft contact lens is a soft contact lens belonging to the soft contact lens classification group IV in principle.
(13) The ophthalmic solution for contact lens according to (11), wherein the soft contact lens is a soft contact lens made of a silicone hydrogel lens material.
(14) The ophthalmic solution for contact lens according to any one of Items (1) to (13), which is used for drying eyes or suppressing dry eyes.
(15) The ophthalmic solution for contact lens according to any one of Items (1) to (13), which is used for improving fatigue sensitivity or contrast sensitivity.

According to the ophthalmic solution for contact lenses of the present invention, it is possible to efficiently stabilize the tear film while wearing contact lenses, and to effectively suppress dry eyes, fatigued eyes, and a decrease in contrast sensitivity.
Moreover, the ophthalmic solution for contact lenses of the present invention also has an effect of reducing stress on the eyes by wearing the contact lenses. Eye dryness and fatigued eyes when wearing contact lenses are also considered to be related to stress on corneal cells, and the effects of eye dryness and fatigued eye improvement by the contact lens ophthalmic solution of the present invention are due to stress caused by contact lens wearing. It seems to be accompanied by mitigation.
Moreover, the ophthalmic solution for contact lenses of the present invention has a good feeling of use, and it is not necessary to prepare the contact lens mounting solution and the ophthalmic solution separately as in the prior art. There is no safety.
Furthermore, there are advantages such as cost reduction in the manufacturing stage, transportation and display efficiency such as reduction in transportation cost in the distribution stage, and improvement in safety of handling of goods in the sales stage. Therefore, the ophthalmic solution for contact lenses of the present invention contributes to the reduction of energy consumption and is useful for energy saving, and also has the effect of reducing adverse effects on the environment.
As described above, according to the present invention, it has excellent effects in suppressing dryness of eyes while wearing contact lenses, improving fatigue eyes, and improving contrast sensitivity, and is highly safe and convenient. In addition, eye drops that can be used to ensure safety and improve efficiency at all stages from manufacturing to sales are provided, leading to improved convenience and safety for contact lens users, manufacturing, transportation, and sales. Efficiency at each stage can be achieved at the same time.

Hereinafter, the present invention will be described in detail.
In this specification, the expression “wearing” represents an action (operation) of “contacting” a contact lens, and the expression “wearing” represents a state where the contact lens is “on the cornea”.
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, “contact lens ophthalmic solution” refers to an ophthalmic composition having both a function as a contact lens mounting solution and a function as an ophthalmic solution that can be instilled while wearing a contact lens. means. Furthermore, the ophthalmic solution of the present invention is an ophthalmic composition that can be used as an ophthalmic solution when the contact lens is worn, and then used as an ophthalmic solution for the eye wearing the contact lens. is there. In this specification, “contact lens ophthalmic solution” may be simply referred to as “wear eye drop”.

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 lens” means “Pharmaceutical Examination No. 645 dated March 31, 1999, Ministry of Health, Labor and Welfare (Ministry of Health, Labor and Welfare)” This is an SCL classification based on “How to classify soft contact lenses” defined in “Handling of materials to be attached when applying for approval of manufacture (import) of disinfectant”. Here, soft contact lenses are classified on the basis of moisture content, mole% of monomers having anions, and the like. For example, SCLs belonging to Group IV have a common property that the moisture content is 50% or more, and the mole% of monomers having anions among the constituent monomers of the raw material polymer is 1% or more. This classification follows the classification method for soft contact lenses performed by the FDA (Food and Drug Administration). Further, "in principle" means that a soft contact lens that can be understood by those skilled in the art as being equivalent to those belonging to the classification in terms of materials, functions, and the like is included.

  A silicone hydrogel contact lens is a silicone-containing material (such as TRIS or a TRIS derivative that is a polymer of silicone and acrylate) and a hydrophilic monomer (such as hydroxyethyl methacrylate, dimethylacrylamide). Contact lenses using polymerized materials, and examples of names of materials based on USAN (United State Adopted Name) include Lotrafilcon A, Lotrafilcon B, Balafilcon A, Galyfilcon A, and Senofilcon A.

  The ophthalmic solution for contact lenses according to the present invention contains (A) one or more selected from the group consisting of a cellulose-based polymer compound, a vinyl-based polymer compound, polyethylene glycol and dextran, and (B) an amino acid. It is characterized by. By containing these components, it is possible to stabilize the tear film while wearing contact lenses and to suppress dryness of the eyes, which is effective in improving fatigue eyes and contrast sensitivity. Can be improved. Further, by using the same formulation of the present invention as a contact lens mounting solution and as an ophthalmic solution, different liquid chemicals are not mixed on the cornea and conjunctiva through the contact lens, and the mechanism has been elucidated in detail. Although there is probably no effect on the eyes and tears due to the interaction between the drug solution and the contact lens, the result is that the tear film is kept in a stable state and is effective in improving fatigue eyes and contrast sensitivity. It is considered to have the above-mentioned effects such as exerting it and having a good usability.

The ophthalmic solution for contact lenses of the present invention is one or more selected from the group consisting of a cellulose polymer compound, a vinyl polymer compound, polyethylene glycol and dextran (hereinafter also simply referred to as component (A). Contains).
Cellulosic polymer compound is a cellulose polymer compound obtained by replacing the hydroxyl group of cellulose with other functional groups, which can impart viscosity to aqueous compositions and is applicable to contact lenses Possible compounds can be used. Examples of the functional group that substitutes 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 the cellulose polymer compound include methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, and salts thereof. Here, the salt is preferably a pharmacologically acceptable salt, more preferably an alkali metal salt, and particularly preferably a sodium salt or a potassium salt. The cellulose polymer used in the present invention is not limited in the degree of substitution and the molecular weight of the substituent. For example, the weight average molecular weight is 50,000 to 1,000,000, preferably 10,000 to 500,000, and more preferably 10,000. About 100,000 can be used. Moreover, a commercially available thing can be used for these cellulose polymer compounds, and you may use it combining 1 type (s) or 2 or more types of these compounds. Among these, from the viewpoint of further enhancing the effects of the present invention, it is preferably at least one selected from the group consisting of methylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, and salts thereof. More preferred are hydroxypropyl methylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, and particularly preferred are hydroxypropylmethylcellulose and hydroxyethylcellulose.

  The content of the cellulosic polymer compound in the ophthalmic solution for contact lenses according to the present invention is not limited because it varies depending on the type and molecular weight of the compound, but for the total amount of ophthalmic solution for contact lenses, The total amount of these compounds is generally 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 1%.

  As the vinyl polymer compound, a compound that can impart viscosity to the aqueous composition and can be applied to contact lenses can be used. Examples of the vinyl polymer compound include a vinyl alcohol polymer such as polyvinyl alcohol (completely or partially saponified product), a vinyl pyrrolidone polymer such as polyvinyl pyrrolidone, and a carboxyvinyl polymer. The molecular weight of the vinyl polymer used in the present invention is not limited, but for example, a weight average molecular weight of 50,000 to 1,000,000, preferably 10,000 to 500,000, more preferably about 10,000 to 400,000 Can be used. These vinyl polymer compounds may be commercially available, or one or more of these compounds may be used in combination. Of these, polyvinyl pyrrolidone K25, polyvinyl pyrrolidone K30, polyvinyl pyrrolidone K90, polyvinyl alcohol (partially saponified product), and carboxyvinyl polymer are preferable from the viewpoint of further enhancing the effects of the present invention, and polyvinyl alcohol (partial) is more preferable. Saponified product) and carboxyvinyl polymer, particularly preferably polyvinyl alcohol (partially saponified product).

  The content of the vinyl polymer compound in the ophthalmic solution for contact lenses according to the present invention is not limited because it varies depending on the type and molecular weight of the compound, but for the total amount of ophthalmic solution for contact lenses, The total amount of these compounds is generally 0.001 to 25%, preferably 0.001 to 10%, more preferably 0.005 to 5%, still more preferably 0.01 to 5%, and particularly preferably 0.1 to 5%. 3%.

  Dextran is a water-soluble polymer compound obtained by partially hydrolyzing a polysaccharide produced by certain lactic acid bacteria using sucrose as a raw material. Dextran having a weight average molecular weight of 50,000 to 1,000,000, preferably 10,000 to 500,000, more preferably about 10,000 to 100,000 can be used. Moreover, these dextrans can use a commercially available thing, and can be used 1 type or in combination of 2 or more types. Of these, dextran, dextran 70, dextran 40, and particularly preferably dextran 70 are preferred from the viewpoint of further enhancing the effects of the present invention.

  The content of dextran in the contact ophthalmic solution for contact lenses in the present invention is generally 0.001 to 25%, preferably 0.001 to 10%, based on the total amount of the ophthalmic solution for contact lenses. Preferably it is 0.01-10%, More preferably, it is 0.01-5%, Most preferably, it is 0.01-1%, More preferably, it is 0.01-0.1%.

  Polyethylene glycol is also referred to as macrogol, and there are no restrictions on the degree of substitution and molecular weight of the substituent, but those having a weight average molecular weight of 100 to 50,000, preferably 400 to 20,000, more preferably about 2000 to 10,000. Can be used. Moreover, these polyethylene glycols can use a commercially available thing, and can be used 1 type or in combination of 2 or more types. Among these, from the viewpoint of further enhancing the effects of the present invention, the macro goal 6000, the macro goal 4000, and the macro goal 400 are preferable, and the macro goal 6000 and the macro goal 4000 are particularly preferable.

  The content of polyethylene glycol in the contact lens mounting ophthalmic solution according to the present invention is generally 0.001 to 25%, preferably 0.001 to 10%, based on the total amount of the contact lens mounting eye drop. More preferably, it is 0.01-10%, More preferably, it is 0.05-5%, Most preferably, it is 0.05-2%.

(A) component in this invention can also be used 1 type or in combination of 2 or more types. From the viewpoint of further enhancing the effects of the present invention, the preferred component (A) is a cellulose-based polymer compound, among which hydroxypropylmethylcellulose and hydroxyethylcellulose are particularly preferable.
In the present invention, the content of the component (A) in the contact lens mounting ophthalmic solution is generally 0.0001 to 25%, preferably 0.001 to 10%, based on the total amount of the contact lens mounting ophthalmic solution. %, More preferably 0.005 to 10%, still more preferably 0.01 to 7%, and particularly preferably 0.01 to 5%.

The wearing ophthalmic solution for contact lenses of the present invention further contains amino acids (hereinafter sometimes simply referred to as component (B)).
The amino acid used in the present invention includes an amino acid or a salt thereof, and an amino acid analog, and means a compound having an amino group and a carboxyl group or a sulfone group in the molecule or a derivative thereof.

  Examples of amino acids include monoamino monocarboxylic acids such as glycine, alanine, aminobutyric acid, aminovaleric acid, and aminocaproic acid; monoaminodicarboxylic acids such as aspartic acid and glutamic acid or salts thereof; diaminomonocarboxylic acids such as arginine and lysine. An acid or a salt thereof; aminoethylsulfonic acid (taurine) or a salt thereof; hyaluronic acid or a salt thereof; 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. Examples of such salts include salts with organic acids [for example, monocarboxylates (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylate (fumarate , Maleate, etc.), oxycarboxylate (lactate, tartrate, citrate, succinate, malonate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, tosylate) Etc.], salts with inorganic acids (eg hydrochlorides, sulfates, nitrates, hydrobromides, phosphates etc.), salts with organic bases (eg methylamine, triethylamine, triethanolamine, Salts with organic amines such as morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), salts with inorganic bases [eg ammonium salts; alkali metals (sodium, potassium, etc.), alkaline earths Metal (calcium, magnesium etc.), etc. and salts with metals such as aluminum] can be exemplified, it is appropriately selected depending on the compound. For example, in the case of 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 L-aspartate (equivalent) Mixture), glutamic acid, glutamic acid hydrochloride, magnesium glutamate, aminoethylsulfonic acid, hyaluronic acid, sodium hyaluronate and the like. More preferred are epsilon aminocaproic acid, potassium aspartate, magnesium aspartate, magnesium / potassium L-aspartate (a mixture of equal amounts), aminoethylsulfonic acid, and sodium hyaluronate. The amino acids of the present invention may be any of D form, L form, and DL form. 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 liquid in the present invention is not limited because it varies depending on the type and molecular weight of the compound, but the total amount of these compounds with respect to the total amount of the contact lens mounting liquid, It is 0.0001 to 10%, preferably 0.001 to 10%, more preferably 0.005 to 8%, further preferably 0.02 to 5% by weight, particularly preferably 0.02 to 3% by weight, and still more preferably 0.05 to 2%.

Furthermore, the wearing ophthalmic solution for contact lenses of the present invention can contain an appropriate nonionic surfactant (hereinafter sometimes simply referred to as component (C)) as required.
As the nonionic surfactant used in the present invention, those that can be used by those skilled in the art for ophthalmic compositions for contact lenses can be used. For example, polyoxyethylene-polysiloxane such as Poloxamer 407, Poloxamer 235, Poloxamer 188, etc. Oxypropylene block copolymer (hereinafter also referred to as polyoxyethylene polyoxypropylene copolymer); POE-POP block copolymer adduct of ethylenediamine such as poloxamine; monolauric acid POE (20) sorbitan (polysorbate 20), monooleic acid POE sorbitan fatty acid esters such as POE (20) sorbitan (polysorbate 80), POE sorbitan monostearate (polysorbate 60), POE sorbitan tristearate (polysorbate 65); POE cured castor oil 5, POE cured castor POE cured castor oils such as oil 10, POE cured castor oil 20, POE cured castor oil 40, POE cured castor oil 50, POE cured castor oil 60, POE cured castor oil 100; POE alkyl such as POE (9) lauryl ether POE (20) POP (4) POE / POP alkyl ethers such as cetyl ether; POE alkyl phenyl ethers such as POE (10) nonyl phenyl ether. POE represents polyoxyethylene, POP represents polyoxypropylene, and the numbers in parentheses indicate the number of moles added.
Among these, polyoxyethylene-polyoxypropylene block copolymers, POE sorbitan fatty acid esters or POE hydrogenated castor oil are preferable, and poloxamer 407, polysorbate 80, and POE hydrogenated castor oil 60 are particularly preferable.

  The content of the nonionic surfactant in the ophthalmic solution for contact lenses according to the present invention varies depending on the type of the surfactant and the like, and thus cannot be specified unconditionally. 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 ophthalmic solution of the present invention preferably contains an appropriate buffer as necessary. Examples of the buffer used in the present invention include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, HEPES buffer, and MOPS buffer. More specifically, boric acid, sodium borate, potassium tetraborate, borax, potassium metaborate, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, carbonic acid, sodium hydrogen carbonate, Examples thereof include compounds such as sodium carbonate, citric 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 buffering agents are borate buffer, phosphate buffer, carbonate buffer and citrate buffer. Particularly preferred buffering agents are borate buffers or phosphate buffers. Particularly preferred buffering agents include, more specifically, boric acid buffers such as boric acid, borate salts such as alkali metal borate salts and alkaline earth metal borate salts, and combinations of boric acid and borate salts. In particular, boric acid and borax are preferable, and phosphate buffering agents include phosphoric acid, phosphates such as alkali metal phosphates and alkaline earth metal phosphates, hydrates thereof, phosphoric acid and The combination with a phosphate is mentioned, Especially sodium hydrogenphosphate, sodium dihydrogenphosphate, and those hydrates are preferable.

  The content of the buffering agent in the ophthalmic solution for contact lenses according to the present invention varies depending on the type of the buffering agent and cannot be defined unconditionally. However, these are the total amount with respect to the total amount of ophthalmic solution for contact lenses. 0.001 to 5%, preferably 0.001 to 3%, more preferably 0.005 to 2.0%, still more preferably 0.005 to 1.5%, and particularly preferably 0.05 to 1.5%. It is.

It is preferable to mix | blend suitable inorganic salt with the eye drop for contact lenses of this invention as needed. Examples of inorganic salts include potassium chloride, sodium chloride, sodium hydrogen carbonate, and sodium carbonate, and these may be used alone or in combination.
The content of inorganic salts in the ophthalmic solution for contact lenses according to the present invention varies depending on the type of inorganic salt and cannot be defined unconditionally. However, these are the total amount of the ophthalmic solution for contact lenses and are usually 0. 0.001 to 5%, preferably 0.01 to 1.5%, more preferably 0.1 to 0.7%.

  The contact lens mounting liquid of the present invention preferably contains an appropriate ethylenediamineacetic acid derivative or a salt thereof as necessary. Examples of such ethylenediamineacetic acid derivatives or salts thereof include edetic acid (ethylenediaminetetraacetic acid, EDTA), ethylenediaminediacetic acid (EDDA), diethylenetriaminepentaacetic acid (DTPA), and N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA). Or the salt etc. can illustrate. Salts of ethylenediamineacetic acid derivatives include pharmacologically or physiologically acceptable salts such as salts with alkali metals (sodium, potassium, etc.) and salts with alkaline earth metals (calcium, etc.). . Among these, ethylenediaminetetraacetic acid or a salt thereof is preferable, such as ethylenediaminetetraacetic acid calcium disodium, ethylenediaminetetraacetic acid disodium, ethylenediaminetetraacetic acid disodium dihydrate (hereinafter also referred to as sodium edetate). Particularly preferred is disodium ethylenediaminetetraacetate dihydrate. These can be used alone or in combination of two or more.

  The content of the ethylenediamineacetic acid derivative or salt thereof in the ophthalmic solution for contact lenses according to the present invention varies depending on the molecular weight and type, etc., but cannot be specified unconditionally, but for the total amount of ophthalmic solution for contact lenses, these are the total amount, Preferably it is 0.0001 to 1%, More preferably, it is 0.0005 to 0.5%, More preferably, it is 0.001 to 0.3%, Most preferably, it is 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 buffering agent in combination.
The content of the ethylenediamineacetic acid derivative or a salt thereof, a nonionic surfactant, an inorganic salt, and a buffer in the ophthalmic solution for contact lenses according to the present invention is the total amount of the ophthalmic solution for contact lenses. 0.01 to 5% is preferable, and 0.05 to 3% is particularly preferable.

  The contact lens ophthalmic solution of the present invention is particularly suitable for use in soft contact lenses among contact lenses. This is because the soft contact lens is easy to feel dry and is easy to put a burden on the eyes. Among them, it is particularly preferable because it is useful for a highly water-containing soft contact lens that is particularly susceptible to dryness, particularly a soft contact lens of soft contact lens classification group IV. Surprisingly, in a soft contact lens made of a silicone hydrogel material, it is preferable to use the soft contact lens in order to exert a remarkable invention effect.

  The ophthalmic solution for contact lenses of the present invention is suitable for containing various components (including pharmacologically active components and physiologically active components) in combination. Decongestant component, ocular muscle modulator component, anti-inflammatory component or astringent component, antihistamine component or antiallergic component, vitamins, acidic mucopolysaccharides, local anesthetic components, etc. that are usually used in ophthalmic compositions It can be illustrated. Specifically, the following components can be exemplified.

Decongestant: For example, α-adrenergic agonists, specifically epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, oxymetazoline hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, epinephrine hydrogen tartrate, naphazoline nitrate. These may be d-form, l-form or dl-form.
Eye muscle modulator component: For example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically, neostigmine methyl sulfate, tropicamide, atropine sulfate helenien, and the like.

  Anti-inflammatory component or astringent component: for example, zinc sulfate, zinc lactate, allantoin, epsilon-aminocaproic acid, indomethacin, lysozyme chloride, silver nitrate, pranoprofen, sodium azulenesulfonate, dipotassium glycyrrhizinate, diclofenac sodium, bromfena Sodium chloride, berberine chloride, berberine sulfate, etc.

  Antihistamine component or antiallergic agent component: for example, acitazanolast, amlexanox, ibudilast, tranilast, diphenhydramine hydrochloride, levocabastine hydrochloride, ketotifen fumarate, sodium cromoglycate, pemirolast potassium, chlorpheniramine maleate, and the like.

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

  Acid mucopolysaccharide: For example, sodium chondroitin sulfate.

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

  In addition, in the ophthalmic solution for contact lenses of the present invention, various components and additives are appropriately selected according to conventional methods according to the use and form within a range not impairing the effects of the invention, and one or more of them are used. You may make it contain. 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, sugar alcohols, Examples thereof include various additives such as acidic mucopolysaccharides, surfactants, preservatives, bactericides or antibacterial agents, pH adjusters, tonicity agents, fragrances or refreshing agents, and stabilizers.

Although the typical component used for the wearing ophthalmic solution for contact lenses of the present invention is illustrated below, it is not limited to these.
Sugars: for example, glucose, cyclodextrin and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like.
Acid mucopolysaccharides: alginic acid, sodium alginate and the like.
Surfactant: For example, in addition to the above-mentioned nonionic surfactants, glycine type amphoteric surfactants such as alkyldiaminoethylglycine; alkyl quaternary ammonium salts (specifically, benzalkonium chloride, benzethonium chloride, etc.) Cationic surfactant etc.) etc.

  Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide or its hydrochloride), polydronium chloride , Glow Kill (trade name, manufactured by Rhodia).

pH adjuster: For example, hydrochloric acid, boric acid, epsilon-aminocaproic acid, acetic acid, sodium hydroxide, sodium hydrogen carbonate, sodium carbonate, borax, triethanolamine, monoethanolamine and the like.
Isotonizing agents: for example, sodium bisulfite, sodium sulfite, magnesium chloride, potassium acetate, sodium acetate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol and the like.

Stabilizer: Dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, etc.
Perfume or refreshing agent: terpenes (for example, anethole, eugenol, camphor, geraniol, cineol, borneol, menthol, limonene, ryuuno, etc. These may be any of d-form, l-form or dl-form), essential oil (Fennel) Oil, cool mint oil, cinnamon oil, spearmint oil, mint water, mint oil, peppermint oil, bergamot oil, eucalyptus oil, rose oil, etc.).

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

  Viscosity is measured by a method using a cone-and-plate rotational viscometer (general test method, 45. Viscosity measurement method, second method rotational viscometer method described in the 14th revised Japanese pharmacy method, “(3) conical According to the method described in the section of “Plate Rotational Viscometer”, specifically, it can be measured using a commercially available cone-plate 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 suitably selected rotor, petroleum carbonization specified by JIS Z8809 for each sample measurement By adjusting hydrogen oil (Newtonian fluid) as a calibration standard solution, the viscosity at 20 ° C. can be measured. Specifically, the viscosity measurement method described in JP-A-2006-348055 is followed (measurement conditions are described later).

  The ophthalmic solution for contact lenses of the present invention is used by adjusting to an osmotic pressure within a range that is acceptable for a living body, if necessary. The osmotic pressure is usually from 0.3 to 4.1, preferably from 0.4 to 4.1, more preferably from 0.3 to 2.1, and particularly preferably from 0.5 to 4.1 as the osmotic pressure ratio with respect to physiological saline. 1.4. For the method of measuring the osmotic pressure ratio, refer to the 15th revised Japanese Pharmacopoeia general test method osmotic pressure measurement method.

  The ophthalmic solution for contact lenses of the present invention is used after adjusting 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. Adjustment of pH can be performed using the said buffer, a pH adjuster, etc.

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

  The method of using the ophthalmic solution for contact lenses of the present invention is as follows: “At the time of wearing a contact lens (immediately before wearing), the ophthalmic solution for contact lens is directly dropped onto the contact lens, and an appropriate amount of both or one side of the contact lens ( For example, it is preferable that the contact lens is used after being wetted with 1 to 2 drops at a time. "(The above brackets are sometimes referred to as" contact lens mounting liquid use ") The method of doing is mentioned. Further, “Use an eye drop of an appropriate amount (for example, preferably 1 to 2 drops at a time) while wearing a contact lens” (inside the above brackets, “the use of eye drops”) (It may be described). The number of instillations per day is not limited, but may be usually in the range of 1 to 10 times, preferably 1 to 6 times, particularly preferably 5 to 6 times.

  Further, as a method of using the ophthalmic solution for contact lenses, a particularly recommended method is as described above, the interval from the use of the contact lens mounting solution to the first instillation after the contact lens is mounted is preferably within 5 hours, preferably Within 2 hours, more preferably within 1 hour, even more preferably within 30 minutes, particularly preferably within 10 minutes, even more preferably within 2 minutes. Subsequent instillation is the same as the use of normal eye drops.

  Furthermore, the present invention includes the following contact lens processing steps. That is: A step of dripping the contact lens mounting ophthalmic solution directly onto the contact lens when the contact lens is mounted (immediately before mounting), 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); 2. The process of wearing a contact lens on the eye; The process of wetting the contact lens by instilling the solution while wearing the contact lens. Furthermore, the present invention can include the following contact lens processing steps. 4). 4. Wetting the contact lens by instilling the liquid when the contact lens is removed from the eye (just before it is removed) The process of removing the contact lens from the eyes, 6. The process of instilling the ophthalmic solution for contact lenses just before wearing the contact lens. In processing the contact lens, an appropriate process may be selected from the above processes as necessary.

  The eye drop for contact lenses of the present invention is preferably used for both contact lens mounting liquid use and eye drop use while wearing a contact lens from the viewpoint of more suitably exerting the effects of the invention. It is intended, but can be used only for either one.

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 examples, the test was performed as continuously as possible in order to make the measurement conditions, particularly the condition of the subject substantially constant. Each test example was performed independently.
In addition, the viscosity of each Example and Comparative Example is the following using TVE-20L type viscometer cone plate type (TOKIMEC, Toki Sangyo (Japan)) which is one type of E type viscometer. Measurement was performed under the measurement conditions according to the manufacturer's instructions. The viscosity measurement method described in JP-A-2006-348055 is followed unless otherwise specified. However, the measurement conditions are as follows.
Measurement condition:
Rotational speed: 100 rpm (In addition, since the allowable range of the rotational speed varies depending on the viscosity, it is measured at the highest rotational speed among the rotational speeds that can be measured according to each prescription.)
Sample volume: 1 ml
Measurement temperature: 20 ° C
Time: Viscosity after 3 minutes was taken as a measured value.

Test 1: Evaluation using a dry eye observation device (DR-1, Kowa Co., Ltd.) (Test method)
According to the prescription in Table 1, the eye drops for each contact lens of Examples 1 to 7 and Comparative Examples 1 to 3 were prepared according to a conventional method for preparing eye drops, etc., and a polyethylene terephthalate container (capacity 10 mL) ) And plugged with a nozzle and a cap. Soft contact lenses are manufactured by Ciba Vision, soft contact lens classification group I (silicone hydrogel lens, main material: Lotrafilcon A) (hereinafter also referred to as SCL1), and Johnson & Johnson, soft contact lens classification group IV Main material: Etafilcon A (hereinafter sometimes referred to as SCL2) was used. After wetting both sides of the contact lens with each eye drop of each prescription, the contact lens was put on, and the eye drop of the same prescription was instilled 2 minutes after wearing.
Thereafter, evaluation was performed according to each test condition of (1) to (3). In addition, the test subject selected 3 people who wear contact lenses on a daily basis and feel dry (persons with a tendency to dry eyes). In addition, after the test for one type of test solution, the test with the next test solution was performed after sufficient rest.

(1) Evaluation of dry spot area-1
Under the conditions described above, the ophthalmic solution for contact lenses was used for use as a contact lens. After that, the solution was instilled while wearing the contact lenses, and then the area of the dry spot was evaluated under the following conditions.
For the observation of the dry spot, a dry eye observation device (DR-1, Kowa Co., Ltd.) that observes the interference color of the tear fluid layer was used. Specifically, the number and size of dry spots on the eye surface 1 second after the start of blinking were measured for blinks about 2 minutes after 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 prescription. Thereafter, the results of 3 subjects were averaged, and the relative value of the total area of each example formulation and comparative example formulation when the total area of Example 1 was 1, was calculated as “relative to the total area of the dry spots. The results are shown in Table 2.

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 as an indicator of dry eyes and dry eyes in the ophthalmic field. Dry spots are short in time, many dry spots, large dry spots, etc. It can be said that it is in a state. From this test result, in the example formulation, the total area of the dry spots was significantly smaller than that in the comparative example formulation. Therefore, it can be said that in the example formulation, 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 remarkably suppressed, indicating an improvement in dry eye symptoms.

(2) Evaluation of dry spot area-2
Under the conditions described above, the ophthalmic solution for contact lenses was used for use as a contact lens. After that, the solution was instilled while wearing the contact lenses, and then the area of the dry spot was evaluated under the following conditions.
Image analysis of the area of the largest dry spot observed from the start of the blink to the start of the next blink for the blink about 11 minutes after instillation using the dry eye observation device (DR-1) The area ratio (%) with respect to the entire observation area on the ocular surface was determined by analysis with an apparatus. In addition, in the case of the comparative example prescription, the dryness progressed particularly 11 minutes after the instillation, and the dry spot was observed in the form of a single dry area. The average value 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 set to 1, and the result is shown as “Evaluation of dry spot area-2”. It was 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 described above, when the dry spot is large, it can be said that the eye is more dry. From this test result, even after a sufficient amount of time has elapsed after instillation, the proportion of the dry spot area is small in the prescriptions of the examples, the tear film on the contact lens surface is stabilized, and eye dryness is remarkable. It shows that it was suppressed. This also indicates an improvement in dry eye symptoms.

(3) Evaluation of tear stability Under the conditions described above, the ophthalmic solution for contact lenses was used for use as a contact lens. After that, the solution was instilled while wearing the contact lens, and then the tear was applied under the following conditions. Stability was evaluated.
About 3 minutes after instillation, the movement of the tear oil layer from the start of the blink to the start of the next blink was observed with a dry eye observation device (DR-1) and scored according to the criteria shown in Table 4 . In addition, the evaluation score was similarly assigned to the movement of the tear oil layer before instillation. In addition, it shows that the oil layer in a tear film is thin or non-uniform | heterogenous, and the tear film is in the unstable state, so that evaluation score is large. The difference in evaluation score before and after instillation was taken as the improvement in tear stability, and the evaluation was made according to the criteria shown in Table 5. Table 7 shows the result of averaging the evaluation scores of 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 hardly disturbed and stable, but in the comparative example formulation, the oil layer in the tear film tends to be disturbed and the tear layer becomes unstable. I understood. As described above, it is known that when the oil layer in the tear film becomes thin, evaporation of the tear liquid is promoted and the eyes are easily dried. Therefore, the above results show that the example prescription significantly suppresses eye dryness as compared with the comparative prescription. This also indicates an improvement in dry eye symptoms.

Test 2: Evaluation of feeling of use
The following evaluation was performed on 10 subjects. The contact lens was worn after wetting both sides of the contact lens with the eye drop. 2 minutes after wearing, after applying the same wearing ophthalmic solution, dry feeling, convergence feeling, unpleasant sticky feeling due to component (A) (nechicha feeling. Unlike mere sticky feeling, eyelids in addition to sticky feeling) The feeling of use corresponding to the feeling of sticking) was scored according to the evaluation criteria shown in Tables 7, 8, and 9. The results of evaluating the average of subjects according to the criteria in Table 10 are shown in Table 11.

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 prescriptions of the examples, as a subjective symptom, a dry feeling, an astringent feeling and a feeling of stickiness were remarkably suppressed.

Test 3: Confirmation of usefulness of combination by prescription According to the prescription in Table 12, for prescriptions 1 to 3, ophthalmic solution, contact lens mounting solution, and contact lens mounting ophthalmic solution were prepared as usual eye drops etc. Method), filled into a polyethylene terephthalate container (capacity 10 mL), and plugged with a nozzle and a cap. In addition, the test methods other than those specified were the same as those in Test 1 and Test 2 described above, and a test for confirming the usefulness of the combination by prescription was performed. Formula 1 and Formula 2 are the formulations of the ophthalmic composition of the present invention. Specifically, Formula 1, Formula 2, and Formula 3 are Example 1, Example 5 and Comparative Example described in Table 1, respectively. 3 and the same prescription. 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 prescription of the present invention is used as a mounting ophthalmic solution (Execution Test Examples 1 and 2) and when a prescription different from the present invention is used as a mounting ophthalmic solution (Comparative Test Example 3), No. 2 had a higher tear oil layer stability and was significantly smaller in the evaluation of the area of the dry spot. Therefore, dryness of the eye was remarkably suppressed. In addition, excellent effects were confirmed in the subjective symptoms of astringency, stickiness, and dryness. Furthermore, even if it is a composition within the scope of the present invention in terms of prescription, when the same composition is used for the same contact lens or eyeball as a wearing ophthalmic solution at the time of wearing and instillation (Example Test 1, Comparing 2) with the case where different compositions were used at the time of wearing and when instilled (Comparative Test Examples 4 and 5), the Test Examples 1 and 2 showed significantly better effects.

Test 4: Evaluation of fatigue eye improvement effect (test method)
Using the contact ophthalmic solution for contact lenses of Formula 1 (the same formulation as Example 1) in Table 12, the fatigue eye improving effect was evaluated. A flicker value was used as an evaluation index.
Specifically, 4 subjects who wear contact lenses for 5 days or more per week and feel tired eyes wear the contact lenses all day for 8 hours or more, and then the flicker value when they wear the contact lenses (Pre-dose flicker value) was measured. The contact lenses used by the subjects are: (1) Johnson & Johnson main material: Senofilcon A (silicone hydrogel material) Soft contact lens classification group IV, (2) Cooper Vision soft contact lens Classification group I Main material: 2-hydroxyethyl methacrylate was 1 person, (3) Oxygen permeable hard contact lens Main material: Siloxanyl styrene was 1 person.

Next, allow enough time, remove the contact lenses for both eyes, and drop the eye drops for contact lenses of prescription 1 directly onto the concave surface of the contact lens (inside, the surface in contact with the cornea). Then, contact lenses were again worn on both eyes, and 15 minutes later, one drop of prescription 1 contact lens ophthalmic solution was instilled into both eyes, and flicker values (flicker values after administration) were measured (practical test). Example 3).
On another day, the pre-dose flicker value was measured in the same manner, and one eye drop of Formula 1 was instilled into both eyes while wearing a contact lens, and 15 minutes later, the eye drop of Formula 1 was applied. Again, one eye drop was applied to both eyes, 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 determined by the following equation (1).
Similarly, the same test was conducted using the contact lens mounting ophthalmic solution of Formulation 4 (same formulation as Example 7) in Table 12 (Example Test Example 4 and Comparative Test Example 7).

The flicker value is a critical frequency at which blinking cannot be identified 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 fatigue and deterioration of perceptual function. That is, improvement of the flicker value is an index of improvement of eye fatigue (particularly eye fatigue caused by physical and mental fatigue accompanied by a decrease in perceptual function) and eye strain.
In this test, the flicker value was measured with the following apparatus and conditions.
Device name: R & D digital flicker value measuring instrument RDF-1 (manufactured by Shibata Kagaku 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
SCAN knob (initial flicker frequency to be lowered): 60Hz
MANU-AUTO: Set to AUTO From the measured flicker value, obtain the fatigue eye improvement value (flicker value improvement rate) using the following equation (1).

  Table 14 shows the average of the results of 4 subjects. As a result, in all of the four subjects, in the experimental test example 3, the flicker value improvement rate was significantly increased as compared with the comparative test example 6. Moreover, in the experimental test example 4, compared with the comparative test example 7, the remarkable increase in the flicker value improvement rate was seen. In this field, it is generally considered that the presence / absence of an effect (clear change) is determined based on a flicker value improvement rate of about 3%. From the above results, the ophthalmic solution for contact lenses of the present invention is more effective in improving fatigue eyes, improving eye strain, or physically and mentally compared with the case of using conventional ophthalmic solutions only for eye drops. It was confirmed that the effect of improving fatigue was remarkably excellent and the utility was high.

Test 5: Evaluation of contrast sensitivity improvement effect (Test method)
Using the contact lens ophthalmic solutions of Examples 1 to 7 in Table 1, the contrast sensitivity improving effect was evaluated.
Specifically, contrast was measured using the Vision Contrast Test System (VCTS (registered trademark)) chart test with 8 subjects wearing contact lenses for 5 days or more per week while wearing contact lenses. Sensitivity was measured (blank). For detailed evaluation methods, reference was made to the instructions attached to the VCTS Chart Exam (VCTS Chart Examination Procedure, Vistech Consultants, Inc.). Further, the contrast sensitivity value was calculated from the table of Contrast Sensitivity Value Key in the same manual. The evaluation points are A (1.5 cpd), B (3 cpd), C (6 cpd), D (12 cpd), and E (18 cpd).
First, the contact lens mounting ophthalmic solution of prescription 1 (= Example 1) in Table 12 was used for contact lens mounting liquid use, and after 2 minutes, the same solution was instilled while wearing the contact lens. After a minute, the contrast sensitivity was measured (Test Example 5). The contact lenses used by the test 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, the contrast sensitivity was remarkably improved in Example 5 in which Prescription 1 was used as a contact lens ophthalmic solution compared to 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, with respect to the ophthalmic solutions for contact lenses of Examples 2 to 7, the contrast sensitivity value was measured at the point B (3 cpd) where the difference was the largest, and the average of the results is shown in Table 15. The contact lenses used by the test subjects were 10 for SCL1 and 10 for SCL2.

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

Formulation Example 1-11
A contact lens wearing ophthalmic solution (Prescription Example 1-15) was prepared according to the formulation shown in Table 16. In Table 16, the unit of each compounding component is g / 100 mL.

It is a graph which shows the improvement effect of the wearing ophthalmic solution for contact lenses of the present invention to the contrast sensitivity fall under wearing of contact lenses.

Claims (8)

(A) One or more selected from the group consisting of cellulose polymer compounds, vinyl polymer compounds, polyethylene glycol and dextran, and (B) aspartic acid, aminoethylsulfonic acid, epsilon aminocaproic acid, hyaluronic acid and the like 1 or more selected from the group consisting of the salt of (A) is contained in a proportion of 0.001 to 10 (w / v)%, and the pH is 4.0 to 9.0. Wearing eye drops for contact lenses,
A contact lens mounting ophthalmic solution having the same composition and used for both the contact lens mounting solution and the ophthalmic solution used while wearing the contact lens. (A) From the group consisting of methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, vinyl alcohol polymer, vinylpyrrolidone polymer, carboxyvinyl polymer and salts thereof One or more selected, and (B) one or more selected from the group consisting of aspartic acid, aminoethylsulfonic acid, epsilon aminocaproic acid, hyaluronic acid and salts thereof, and a pH of 4.0 to 4.0 A contact lens ophthalmic solution of 9.0,
A contact lens mounting ophthalmic solution having the same composition and used for both the contact lens mounting solution and the ophthalmic solution used while wearing the contact lens.   The ophthalmic solution for contact lenses according to claim 1, wherein the component (A) is a cellulosic polymer compound. The ophthalmic solution for contact lens according to claim 3 , wherein the cellulose polymer is at least one selected from the group consisting of hydroxyethylcellulose, hydroxypropylmethylcellulose, and salts thereof. The ophthalmic solution for contact lenses according to claim 2 , comprising the component (A) at a ratio of 0.0001 to 25 (w / v)%. The ophthalmic solution for contact lens according to any one of claims 1 to 5 , wherein the component (B) is contained at a ratio of 0.0001 to 10 (w / v)%. Furthermore, the ophthalmic solution for contact lenses according to any one of claims 1 to 6 , further comprising (C) a nonionic surfactant. The ophthalmic solution for contact lenses according to any one of claims 1 to 7 , which is used for dry eyes or for dry eye suppression.

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