JP5650864B2 - Nonionic silicone hydrogel contact lens ophthalmic composition - Google Patents

Description

  The present invention relates to an ophthalmic composition for a nonionic silicone hydrogel contact lens that can suppress lipid adsorption to the nonionic silicone hydrogel contact lens. The present invention also relates to a method for suppressing lipid adsorption to a nonionic silicone hydrogel contact lens. Furthermore, the present invention relates to a method for suppressing the adhesion of corneal cells to the surface of a nonionic silicone hydrogel contact lens.

In recent years, the number of wearers of contact lenses (CL) has increased, and in particular, the number of wearers of soft contact lenses (SCL) has increased. In general, it has been pointed out that when a soft contact lens is worn, the amount of oxygen supplied from the atmosphere decreases, which may result in suppression of corneal epithelial cell division and thickening of the cornea. Therefore, development of soft contact lenses having higher oxygen permeability has been advanced.

  Under such circumstances, silicone hydrogel contact lenses have been developed in recent years as soft contact lenses having high oxygen permeability. Silicone hydrogel contact lenses achieve oxygen permeability several times that of conventional hydrogel contact lenses by blending silicone with hydrogel. Therefore, it is highly expected that the oxygen supply shortage, which is a weak point of the soft contact lens, can be improved and the adverse effects on the cornea due to the oxygen shortage can be greatly suppressed.

On the other hand, it has been pointed out that silicone hydrogel contact lenses are more likely to be contaminated with lipids derived from tear film, cosmetics and the like as compared with conventional hydrogel contact lenses (Non-patent Document 1). Such lipid contamination induces cloudiness of the lens, causing discomfort to the wearer and harming the quality of life (QOL). Further, such contamination of the contact lens may adversely affect the vision correction power that the lens should originally have. Furthermore, in recent years, it has also been pointed out that such lipid contamination of contact lenses affects the occurrence of corneal epithelial disorder called corneal staining.

  In general, it is indispensable to design an ophthalmic composition used for a contact lens in consideration of safety and other effects depending on the type of contact lens. In particular, soft contact lenses vary in the presence or absence of ionicity and the level of water content depending on the material, so ophthalmic compositions used for soft contact lenses are designed according to the characteristics of the target soft contact lens. It is important to do it.

On the other hand, vitamins B6, vitamin E, and vitamin A have been used in ophthalmic compositions for the purpose of accelerating the metabolism of eye cells and relieving eye fatigue. However, due to the difficulty in designing the formulation of the ophthalmic composition used for the soft contact lens as described above, vitamin B6, vitamin E, or the like that can be used when wearing SCL (including silicone hydrogel contact lenses), or Ophthalmic compositions containing vitamin A have not been commercially available so far.

  Until now, the influence of vitamin B6, vitamin E, or vitamin A on the silicone hydrogel contact lens is not known at all. Moreover, from the prior art, it is not possible to estimate the influence of a specific combination of these components on the silicone hydrogel contact lens at all.

Hiroshi Shiotani, New Ophthalmology Vol.25, No.7, 907-912, 2008

As a result of various studies on the lipid adsorption characteristics of various soft contact lenses, the present inventors have found that nonionic silicone hydrogel contact lenses (hereinafter sometimes referred to as nonionic SHCL) are soft contact lenses. In particular, it was confirmed that lipids are remarkably easily adsorbed. Such significant lipid stains can cause clouding of the lens, harming the wearer's QOL (Quality of Life), and may also adversely affect the vision correction ability of the lens. Furthermore, such lipid stains may induce corneal epithelial disorders such as corneal staining. Therefore, by suppressing lipid adsorption to nonionic SHCL, it prevents the cloudiness of the lens and improves the feeling of wearing, maintains the original vision correction power of the lens, further prevents corneal epithelial disorder, There is a need for the development of means that make it possible to use non-ionic SHCL comfortably and safely. Then, an object of this invention is to provide the ophthalmic composition for nonionic SHCL which can suppress the lipid adsorption | suction to nonionic SHCL.

  As a result of intensive studies to solve the above problems, the present inventors have combined (A) vitamin B6 and (B) at least one selected from the group consisting of vitamin E and vitamin A. It has been found that by using it, lipid adsorption to nonionic SHCL can be remarkably suppressed. Furthermore, the present inventors proceeded with investigations and found that the combined use of the above components (A) and (B) can effectively suppress the adhesion of corneal epithelial cells to nonionic SHCL. The present invention has been completed by making further improvements based on such findings.

That is, the present invention provides the following ophthalmic compositions for nonionic SHCL.
Item 1-1. An ophthalmic composition for nonionic silicone hydrogel contact lenses, comprising (A) vitamin B6 and (B) at least one selected from the group consisting of vitamin E and vitamin A.
Item 1-2. Item 10. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to Item 1-1, which contains at least one selected from the group consisting of pyridoxine and a salt thereof as the component (A).
Item 1-3. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to Item 1-1 or 1-2, which contains pyridoxine hydrochloride as the component (A).
Item 1-4. Item 4. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to any one of Items 1-1 to 1-3, wherein the component (A) is contained in a total amount of 0.001 to 1.0 w / v%.
Item 1-5. Item 5. The nonionic silicone hydrogel contact lens according to any one of Items 1-1 to 1-4, comprising as component (B) at least one selected from the group consisting of tocopherol, a derivative thereof, and a salt thereof. Ophthalmic composition.
Item 1-6. Item 5. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to any one of Items 1-1 to 1-5, which comprises tocopherol acetate as a component.
Item 1-7. Item (B) The nonionic silicone hydrogel contact lens according to any one of Items 1-1 to 1-6, which comprises at least one selected from the group consisting of retinol, derivatives thereof, and salts thereof. Ophthalmic composition.
Item 1-8. The ophthalmic composition for a nonionic silicone hydrogel contact lens according to any one of Items 1-1 to 1-7, comprising (B) at least one selected from the group consisting of retinol palmitate and retinol acetate object.
Item 1-9. Item 9. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to any one of Items 1-1 to 1-8, wherein the component (B) is contained in a total amount of 0.0003 to 0.5 w / v%.
Item 1-10. Item 10. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to any one of Items 1-1 to 1-9, further comprising a surfactant.
Item 1-11. Item 10. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to Item 1-10, which contains a nonionic surfactant as a surfactant.
Item 1-12. Item 10. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to Item 1-10 or 1-11, which contains a surfactant in a total amount of 0.001 to 1.0 w / v%.
Item 1-13. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to any one of Items 1-1 to 1-12, further comprising a buffer.
Item 1-14. Item 14. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to Item 1-13, which contains a borate buffer as a buffer.
Item 1-15. Item 15. The ophthalmic composition for a nonionic silicone hydrogel contact lens according to Item 1-13 or 1-14, comprising a buffering agent in a total amount of 0.01 to 10 w / v%.
Item 1-16. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to any one of Items 1-1 to 1-15, further comprising an isotonic agent.
Item 1-17. Item 15. The nonionic silicone hydrogel contact according to Item 1-16, which contains at least one selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerin, and propylene glycol as an isotonic agent. Ophthalmic composition for lenses.
Item 1-18. Item 18. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to Item 1-16 or 1-17, which contains an isotonic agent in a total amount of 0.01 to 10 w / v%.
Item 1-19 The ophthalmic composition for nonionic silicone hydrogel contact lenses according to any one of Items 1-1 to 1-18, which is an eye drop.

Moreover, this invention provides the method of suppressing the lipid adsorption | suction to nonionic SHCL hung up below.
Item 2. A composition containing (A) vitamin B6 and (B) at least one selected from the group consisting of vitamin E and vitamin A is brought into contact with a nonionic silicone hydrogel contact lens. And a method for suppressing lipid adsorption to a nonionic silicone hydrogel contact lens.

The present invention also provides a method for imparting an ophthalmic composition with the action of suppressing lipid adsorption to the nonionic SHCL listed below.
Item 3. A nonionic silicone hydrogel contact lens ophthalmic composition is characterized in that it contains (A) vitamin B6 and (B) at least one selected from the group consisting of vitamin E and vitamin A. And a method for imparting an action of suppressing lipid adsorption to a nonionic silicone hydrogel contact lens to the ophthalmic composition.

The present invention also provides a method for suppressing adhesion of corneal epithelial cells to nonionic SHCL described below.
Item 4. A composition containing (A) vitamin B6 and (B) at least one selected from the group consisting of vitamin E and vitamin A is brought into contact with a nonionic silicone hydrogel contact lens. A method for suppressing adhesion of corneal epithelial cells to a nonionic silicone hydrogel contact lens.

The present invention also provides a method for imparting an ophthalmic composition with an adhesion inhibitory action of corneal epithelial cells on nonionic SHCL listed below.
Item 5. A nonionic silicone hydrogel contact lens ophthalmic composition is characterized in that it contains (A) vitamin B6 and (B) at least one selected from the group consisting of vitamin E and vitamin A. A method for imparting an adhesion suppressing action of corneal epithelial cells to a nonionic silicone hydrogel contact lens to the ophthalmic composition.

  The ophthalmic composition for nonionic SHCL of the present invention can remarkably suppress lipid adsorption to nonionic SHCL. Therefore, according to the ophthalmic composition for nonionic SHCL of the present invention, nonionic SHCL lipid stains can be prevented, and nonionic SHCL cloudiness can be prevented. In addition, it effectively prevents corneal epithelial disorders such as corneal staining caused by lipid adsorption to nonionic SHCL, making it possible to use nonionic SHCL comfortably and safely Become.

In addition, the non-ionic SHCL has a characteristic characteristic that corneal cells are remarkably easy to adhere, according to the study by the present inventors, but the non-ionic SHCL ophthalmic composition for the non-ionic SHCL of the present invention. According to this, corneal cell adhesion to nonionic SHCL can be effectively suppressed. A contact lens with high adhesion of corneal epithelial cells peels off the cells from the eye tissue every time the lens moves on the cornea due to adhesion of the corneal cells to the lens while wearing the contact lens, or when the lens is removed. As a result, the corneal surface may be damaged and the pain associated therewith may occur, and as a result, the quality of life (QOL) of the contact lens user may be significantly reduced. Therefore, according to the ophthalmic composition for nonionic SHCL of the present invention, the adhesion of corneal cells to nonionic SHCL can be suppressed, so that wearing nonionic SHCL with high safety (for example, for a long time) It can also be worn continuously).

  As described above, the ophthalmic composition for nonionic SHCL of the present invention can solve various problems that are a concern when wearing nonionic SHCL, and ensures high safety and comfort in the use of nonionic SHCL. can do.

In the reference test example 1, it is a figure which shows the result of having evaluated the adsorption | suction characteristic of the lipid in various soft contact lenses. In Test Example 1, it is a figure which shows the result of having evaluated the influence which acts on adsorption | suction of the lipid to nonionic SHCL about a test liquid (Example 1-3 and Comparative Example 1-4). In Test Example 2, it is a figure which shows the result of having evaluated the influence which acts on adsorption | suction of the lipid to nonionic SHCL about a test liquid (Example 4-6 and Comparative Example 5). In the reference test example 2, it is a figure which shows the result of having evaluated the adhesiveness of the corneal epithelial cell of various soft contact lenses. In Test Example 3, it is a figure which shows the result of having evaluated the corneal epithelial cell adhesion inhibitory effect with respect to nonionic SHCL of a test liquid (Example 7-8 and Comparative Example 6-8).

1. Nonionic SHCL Ophthalmic Composition The nonionic SHCL ophthalmic composition of the present invention contains vitamin B6 (hereinafter also referred to as component (A)).

  Vitamin B6 is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and specific examples thereof include pyridoxine, pyridoxal, pyridoxamine, and salts thereof. It is done.

Of the component (A) used in the present invention, the form of the salt is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Is an organic acid salt [eg, monocarboxylate (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylate (fumarate, maleate, succinic acid, etc. Salt, malonate, etc.), oxycarboxylate (lactate, tartrate, citrate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, tosylate, etc.)], inorganic acid Salts (for example, hydrochloride, sulfate, nitrate, hydrobromide, phosphate, etc.). Among these salts, preferred are inorganic acid salts, more preferred are hydrochlorides and phosphates, and particularly preferred are hydrochlorides. These pyridoxine, pyridoxal, and pyridoxamine salts may be used alone or in any combination of two or more.

  These vitamin B6s may be used alone or in any combination of two or more. Among these vitamin B6s, pyridoxine and its salt, preferably pyridoxine and its inorganic acid salt, more preferably pyridoxine hydrochloride, from the viewpoint of more effectively suppressing lipid adsorption to nonionic SHCL. Examples thereof include salts and pyridoxine phosphate, particularly preferably pyridoxine hydrochloride (pyridoxine hydrochloride). The vitamin B6 exemplified here is also suitable from the viewpoint of further enhancing the adhesion suppressing effect of corneal epithelial cells on nonionic SHCL.

In the nonionic SHCL ophthalmic composition of the present invention, the blending ratio of the component (A) is appropriately set according to the type of the component (A), the formulation form of the nonionic SHCL ophthalmic composition, and the like. As an example, with respect to the total amount of the ophthalmic composition for nonionic SHCL, the total amount of the component (A) is 0.001-1.
. 0 w / v%, preferably 0.01 to 0.5 w / v%, more preferably 0.02 to 0.2 w / v%
Is exemplified.

In addition to the above component (A), the ophthalmic composition for nonionic SHCL of the present invention includes vitamin Es (hereinafter sometimes referred to as (B-1) component) and vitamin As (hereinafter referred to as ( B-2) component ”(hereinafter, the components (B-1) and (B-2) may be collectively referred to as the component (B)). Thus, by using the components (A) and (B) together, it is possible to effectively suppress lipid adsorption to nonionic SHCL, and effective adhesion of corneal epithelial cells to nonionic SHCL. It is also possible to suppress it.

The vitamin E used as the component (B-1) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specifically, tocopherol, Tocotrienols, and their derivatives, and their salts. The tocopherol and tocotrienol may be any of α-, β-, γ-, and δ-, and may be either d-form or dl-form. Tocopherol is preferable, α-tocopherol is more preferable, and dl-α-tocopherol is still more preferable.

Among the components (B-1), examples of the derivative include tocopherol organic acid esters such as tocopherol acetate, tocopherol succinate, tocopherol nicotinate and tocopherol linolenate. One of these derivatives may be selected and used alone, or two or more may be used in any combination.

In addition, among the components (B-1), the form of the salt is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specifically, Salts with organic bases (for example, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), salts with inorganic bases [for example, ammonium salts; alkali metals ( Sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), salts with metals such as aluminum, etc.]. One of these salts may be selected and used alone, or two or more may be used in any combination.

In the ophthalmic composition for nonionic SHCL of the present invention, when the component (B-1) is used, one kind of vitamin E may be selected and used alone, or two or more kinds may be used. These may be used in any combination. Among these (B-1) components, from the viewpoint of more effectively suppressing lipid adsorption to nonionic SHCL, preferably tocopherol, its derivatives, and salts thereof, more preferably tocopherol derivatives, Tocopherol organic acid esters are preferable, and tocopherol acetate is particularly preferable. The vitamin Es exemplified here are also suitable from the viewpoint of further enhancing the effect of suppressing the adhesion of corneal epithelial cells to nonionic SHCL.

The vitamin A used as the component (B-2) is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. Specifically, retinol ( Examples include vitamin A1), 3-dehydroretinol (vitamin A2), and derivatives thereof, and salts thereof.

Among the components (B-2), as derivatives, for example, retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, retinol octylate, retinol laurate, retinol oleate, retinol linolenate, retinal, retinoic acid , Retinoic acid methyl, retinoic acid ethyl, retinoic acid retinol, δ-tocopheryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate and the like. One of these derivatives may be selected and used alone, or two or more may be used in any combination.

Further, among the components (B-2), the form of the salt is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specifically, The same form as the salt which the said vitamin B6 and vitamin E can take is illustrated. One of these salts may be selected and used alone, or two or more may be used in any combination.

In the ophthalmic composition for nonionic SHCL of the present invention, when component (B-2) is used, one of vitamin A may be selected and used alone, or two or more These may be used in any combination. Among these (B-2) components, from the viewpoint of more effectively suppressing lipid adsorption to nonionic SHCL, preferably retinol, its derivatives, and salts thereof, more preferably retinol acetate and palmitic acid. Retinol, particularly preferably retinol palmitate is mentioned. The vitamin A exemplified here is also suitable from the viewpoint of further enhancing the effect of suppressing the adhesion of corneal epithelial cells to nonionic SHCL.

In the ophthalmic composition for nonionic SHCL of the present invention, as the component (B), one of the above components (B-1) and (B-2) may be used alone, or 2 More than one species may be used in any combination. Among these (B) components, from the viewpoint of more effectively suppressing lipid adsorption to nonionic SHCL, preferably (B-1) component, or (B-1) and (B-2) components In combination with;
More preferably (B-1) a derivative of tocopherol and a salt thereof, or (B-2) a combination of a derivative of retinol and a salt thereof and (B-1) a derivative of tocopherol and a salt thereof; ) Tocopherol acetate, or (B-2) a combination of retinol palmitate and (B-1) tocopherol acetate; particularly preferably (B-2) a combination of retinol palmitate and (B-1) tocopherol acetate. The The component (B) exemplified here is also suitable from the viewpoint of further enhancing the effect of suppressing the adhesion of corneal epithelial cells to nonionic SHCL.

In the ophthalmic composition for nonionic SHCL of the present invention, for the blending ratio of component (B), the type of component (A), the type of component (B), the formulation form of the ophthalmic composition for nonionic SHCL, etc. However, as an example, the total amount of component (B) is 0.0003 to 0.5 w / v%, preferably 0.0015 to the total amount of the nonionic SHCL ophthalmic composition. An example is 0.05 w / v%. More specifically, the following ranges are exemplified as the blending ratio of each component (B) with respect to the total amount of the nonionic SHCL ophthalmic composition:
When it is the component (B-1), the total amount of the component (B-1) is 0.001 to 0.5 w / v%, preferably 0.005 to 0.1 w / v%, more preferably 0.01 to 0.05w / v%;
In the case of component (B-2), the total amount of component (B-2) is 0.0003 to 0.165 w / v% (corresponding to about 1000 to 300,000 IU / 100 mL), preferably 0.0009 to 0.055 w. / v% (equivalent to about 3000 to 100000 IU / 100 mL), more preferably 0.0015 to 0.0275 w / v% (equivalent to about 5000 to 50000 IU / 100 mL).

Here, IU is an international unit related to the amount of vitamin A, as can be generally understood by those skilled in the art. For example, in the case of retinol, 1 IU corresponds to about 0.30 μg of retinol,
In the case of retinol acetate, it is well known that 1 IU = about 0.34 μg of retinol acetate, and in the case of retinol palmitate, 1 IU = about 0.55 μg of retinol palmitate.

Further, in the ophthalmic composition for nonionic SHCL of the present invention, the ratio of the component (B) to the component (A) is not particularly limited, but the lipid adsorption to the nonionic SHCL is more effective. From the viewpoint of suppressing the total amount of component (A), the range in which the total amount of component (B) is 0.2 to 2500 parts by weight, preferably 2 to 250 parts by weight per 100 parts by weight of the total amount of component (A) is exemplified. More specifically, examples of the ratio of the component (B) per 100 parts by weight of the total amount of the component (A) include the following ranges:
When it is the component (B-1), the total amount of the component (B-1) is 0.5 to 2500 parts by weight, preferably 2.5 to 500 parts by weight, more preferably 5 to 250 parts by weight;
In the case of component (B-2), the total amount of component (B-2) is 0.275 to 825 parts by weight, preferably 1.375 to 275 parts by weight, and more preferably 2.75 to 137.5 parts by weight.

  By satisfying the above ratio, it is possible to further enhance the effect of suppressing the adhesion of corneal epithelial cells to nonionic SHCL.

  The ophthalmic composition for nonionic SHCL of the present invention may further contain a surfactant. The surfactant that can be incorporated into the ophthalmic composition for nonionic SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and is nonionic. Any of an ionic surfactant, an amphoteric surfactant, an anionic surfactant, and a cationic surfactant may be used.

Specific examples of the nonionic surfactant that can be incorporated into the ophthalmic composition for nonionic SHCL of the present invention include POE (20) sorbitan monolaurate (polysorbate 20), POE monopalmitate POE (20) sorbitan ( POE sorbitan fatty acid esters such as polysorbate 40), monostearic acid POE (20) sorbitan (polysorbate 60), tristearic acid POE (20) sorbitan (polysorbate 65), monooleic acid POE (20) sorbitan (polysorbate 80); POE / POP block copolymers such as Poloxamer 407, Poloxamer 235, Poloxamer 188, Poloxamer 403, Poloxamer 237, Poloxamer 124; POE cured castor oils such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE alkyl ethers such as POE (9) lauryl ether; POE-POP alkyl such as POE (20) POP (4) cetyl ether Ether compounds; POE (10) POE alkylphenyl ethers such as nonylphenyl ether. In the compounds exemplified above, POE is polyoxyethylene, POP is polyoxypropylene, and the numbers in parentheses indicate the number of moles added. Specific examples of the amphoteric surfactant that can be incorporated into the ophthalmic composition for nonionic SHCL of the present invention include alkyldiaminoethylglycine. Specific examples of the cationic surfactant that can be blended in the nonionic SHCL ophthalmic composition of the present invention include benzalkonium chloride and benzethonium chloride. Specific examples of the anionic surfactant that can be blended in the ophthalmic composition for nonionic SHCL of the present invention include alkylbenzene sulfonate, alkyl sulfate, polyoxyethylene alkyl sulfate, and aliphatic α. -Sulfomethyl ester, α-olefin sulfonic acid and the like are exemplified.

  In the ophthalmic composition for nonionic SHCL of the present invention, the surfactant may be used alone or in combination of two or more.

Among the above surfactants, preferably nonionic surfactants; more preferably POE sorbitan fatty acid esters, POE hydrogenated castor oil, or POE / POP block copolymers;
More preferred are POE sorbitan fatty acid esters and POE hydrogenated castor oil; particularly preferred are polysorbate 80 and polyoxyethylene hydrogenated castor oil 60.

When a surfactant is blended in the ophthalmic composition for nonionic SHCL of the present invention, the blending ratio of the surfactant is the type of the surfactant, the type and amount of other blending components, the nonionic SHCL. It can set suitably according to the formulation form etc. of an ophthalmic composition. As an example of the blending ratio of the surfactant, the total amount of the surfactant is 0.001 to 1.0 w / v%, preferably 0.005 to 0 with respect to the total amount of the nonionic SHCL ophthalmic composition. .7w / v%, more preferably 0.01 to 0.5w / v%
Is exemplified.

The ophthalmic composition for nonionic SHCL of the present invention may further contain a buffer. The buffer that can be incorporated into the ophthalmic composition for nonionic SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such buffers include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, tris buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like. These buffering agents may be used in combination. Preferred buffering agents are borate buffer, phosphate buffer, carbonate buffer, and citrate buffer, and more preferred are borate buffer and phosphate buffer, and particularly preferred buffer. Is a borate buffer. Examples of the boric acid buffer include boric acid or boric acid salts such as alkali metal borate and alkaline earth metal borate. Examples of the phosphate buffer include phosphoric acid or phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Examples of the carbonate buffer include carbonates or carbonates such as alkali metal carbonates and alkaline earth metal carbonates. Examples of the citrate buffer include citric acid, alkali metal citrate, and alkaline earth metal citrate. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. As a more specific example, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.)
; Phosphoric acid or a salt thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, diphosphate phosphate; Carbonic acid or a salt thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.); Citric acid or a salt thereof as a citrate buffer Salt (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetic acid or a salt thereof (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.) as an acetate buffer ; Tris (hydroxymethyl) aminometa as a Tris buffer Or a salt thereof (hydrochloride, acetate, sulfonate, etc.); aspartic acid or a salt thereof (sodium aspartate, magnesium aspartate, potassium aspartate, etc.) and the like. Among these buffering agents, boric acid buffering agents are preferably used for the non-ionic SHCL ophthalmic composition of the present invention because they are expected to exhibit the effects of the present invention more reliably. These buffering agents may be used alone or in any combination of two or more.

When a buffering agent is blended in the nonionic SHCL ophthalmic composition of the present invention, the blending ratio of the buffering agent is the type of buffering agent used, the type and amount of other blending components, and the formulation of the ophthalmic composition. Depending on the form and the like, it cannot be uniformly defined. For example, the total amount of the buffer is 0.01 to 10 w / v%, preferably 0 with respect to the total amount of the nonionic SHCL ophthalmic composition. A ratio of 1 to 5 w / v%, more preferably 0.5 to 2 w / v% is exemplified.

  The ophthalmic composition for nonionic SHCL of the present invention may further contain an isotonic agent. The isotonic agent that can be incorporated into the ophthalmic composition for nonionic SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of such isotonic agents include, for example, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, acetic acid Examples include potassium, sodium acetate, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol and the like. Among these isotonic agents, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerin, and propylene glycol are preferable from the viewpoint of more reliably achieving the effects of the present invention. These isotonic agents may be used alone or in any combination of two or more.

  When an isotonic agent is blended in the nonionic SHCL ophthalmic composition of the present invention, the blending ratio of the tonicity agent varies depending on the type of tonicity agent to be used, etc., and is uniformly defined. For example, the proportion of the tonicity agent is 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%, more preferably 0.1 to 3 w / v% in total. Illustrated.

  The pH of the ophthalmic composition for nonionic SHCL of the present invention is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable range. As an example of the pH of the ophthalmic composition for nonionic SHCL of the present invention, a range of 4.0 to 9.5, preferably 5.0 to 9.0, and more preferably 5.5 to 8.5 is given. It is done.

  Further, the osmotic pressure of the ophthalmic composition for nonionic SHCL of the present invention is not particularly limited as long as it is within a range acceptable for a living body. As an example of the osmotic pressure ratio of the ophthalmic composition for nonionic SHCL of the present invention, preferably 0.5 to 5.0, more preferably 0.6 to 3.0, particularly preferably 0.7 to 2.0. The range becomes. The osmotic pressure can be adjusted by a method known in the art using inorganic salts, polyhydric alcohols, sugar alcohols, saccharides and the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 15th revised Japanese pharmacopoeia. Measure with reference to the descent method. The standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) was dried in sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 ° C. for 40 to 50 minutes and then released in a desiccator (silica gel). Cool and accurately measure 0.900 g and dissolve in purified water to make exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).

The ophthalmic composition for nonionic SHCL of the present invention may contain an appropriate amount of various pharmacologically active components and physiologically active components in addition to the above components as long as the effects of the present invention are not hindered. Such an ingredient is not particularly limited, and examples thereof include an active ingredient in an ophthalmic drug described in the over-the-counter drug manufacturing (import) approval standard 2000 edition (supervised by the Pharmaceutical Affairs Research Committee). Specifically, the following components are listed as components used in ophthalmic drugs.
Antihistamines: for example, iproheptin, diphenhydramine hydrochloride, chlorpheniramine maleate, ketotifen fumarate, pemirolast potassium and the like.
Decongestant: For example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline sulfate, epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, and the like.
Fungicide: For example, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, polyhexamethylene biguanide hydrochloride, and the like.
Vitamins: For example, flavin adenine dinucleotide sodium, cyanocobalamin, panthenol, calcium pantothenate and the like.
Amino acids: For example, potassium aspartate, magnesium aspartate, aminoethylsulfonic acid and the like.
Anti-inflammatory agents: for example, dipotassium glycyrrhizinate, pranoprofen, allantoin, azulene, sodium azulenesulfonate, guaiazulene, ε-aminocaproic acid, berberine chloride, berberine sulfate, lysozyme chloride, licorice, etc.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Other: For example, sodium cromoglycate, sodium chondroitin sulfate, sulfamethoxazole, sulfamethoxazole sodium and the like.

In addition, in the ophthalmic composition for nonionic SHCL of the present invention, various additives are appropriately selected according to a conventional method according to the use and form as long as the effects of the invention are not impaired. Or you may make it contain in an appropriate amount using together or more. Examples of these additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Carrier: An aqueous carrier such as water or hydrous ethanol.
Thickeners: for example, carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, alginic acid, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol and the like.
Sugars: For example, cyclodextrins and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.
Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, etc.), Glowyl (manufactured by Rhodia) Name) etc.
pH adjuster: for example, hydrochloric acid, boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, boro Sand, triethanolamine, monoethanolamine, diisopropanolamine, sulfuric acid, phosphoric acid, polyphosphoric acid, propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, gluconolactone, ammonium acetate etc.
Stabilizers: for example, dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate and the like.
Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), and the like.
Perfume or refreshing agent: for example, menthol, anethole, eugenol, camphor, geraniol, cineol, borneol, limonene, ryuno and the like. These may be either d-form, l-form or dl-form, and are formulated as essential oils (mint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil, etc.) May be.

  The ophthalmic composition for nonionic SHCL of the present invention is prepared by adding a desired amount of the above components (A) and (B) and, if necessary, other compounding components to a desired concentration. .

  The dosage form of the nonionic SHCL ophthalmic composition of the present invention is not particularly limited as long as it can be used in the ophthalmic field, and examples thereof include liquids and ointments. Among these, liquid is preferable. Of the liquids, aqueous liquids are preferred. When the non-ionic SHCL ophthalmic composition of the present invention is made into an aqueous liquid, pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable water may be used as an aqueous carrier. Specific examples include distilled water, normal water, purified water, sterilized purified water, water for injection, distilled water for injection, and the like. These definitions are based on the 1st 5th Japanese Pharmacopoeia. Here, the aqueous liquid means a liquid form containing water, and usually 1% by weight or more, preferably 5% by weight or more, more preferably 20% by weight of water in the nonionic SHCL ophthalmic composition. It means that containing at least 50% by weight, more preferably at least 50% by weight.

  The ophthalmic composition for nonionic SHCL of the present invention is not limited as long as it is used in the ophthalmic field and used to come into contact with nonionic SHCL. For example, eye drops for nonionic SHCL (eye drops that can be used while wearing nonionic SHCL), eye drops for nonionic SHCL (eyewash that can be used while wearing nonionic SHCL), nonionic Nonionic SHCL care solution (nonionic SHCL disinfectant, nonionic SHCL preserving solution, nonionic SHCL cleaning solution, nonionic SHCL cleaning preservative solution, etc.) and the like.

  Among these, the eye drops for nonionic SHCL can be easily used during wearing of nonionic SHCL, so that it is possible to effectively suppress the adhesion of lipid stains during wearing of nonionic SHCL, and nonionic SHCL. This is preferable in that the non-ionic SHCL can be worn comfortably by preventing clouding and discomfort of the lens during wearing. In addition, non-ionic SHCL eye drops or non-ionic SHCL mounting solutions, in particular non-ionic SHCL eye drops, are used when the non-ionic SHCL is in contact with the surface of the eyeball or immediately before contact (for example, contact). It is used within 10 minutes before the wearing action to be performed), and is a pharmaceutical form in which the action of suppressing the adhesion of corneal epithelial cells to nonionic SHCL is strongly required. And an eye drop can exhibit the effect of this invention much more effectively also in the point that it is a formulation with high use frequency per day compared with other ophthalmic compositions generally. Considering these viewpoints comprehensively, a nonionic SHCL ophthalmic solution is mentioned as a suitable example of the ophthalmic composition for nonionic SHCL of the present invention.

  Further, the method for using the nonionic SHCL ophthalmic composition of the present invention is particularly limited as long as it is a known method having a step of bringing the nonionic SHCL ophthalmic composition into contact with the nonionic SHCL. There is no. For example, in the case of eye drops for nonionic SHCL, an appropriate amount of the eye drops may be instilled before or during wearing of nonionic SHCL. In the case of a nonionic SHCL eye wash, an appropriate amount of the eye wash may be used for eye washing before or during wearing of the nonionic SHCL. In addition, when the ophthalmic composition for nonionic SHCL of the present invention is a nonionic SHCL eye drop or a nonionic SHCL eyewash, when wearing nonionic SHCL, of course, it is not worn. Even at times, it can be used for eye drop and eye wash purposes. In the case of a nonionic SHCL mounting solution, the nonionic SHCL is used by contacting an appropriate amount of the mounting solution with the nonionic SHCL when the nonionic SHCL is mounted. Furthermore, in the case of a nonionic SHCL care solution, the nonionic SHCL is immersed in an appropriate amount of the care solution, or the nonionic SHCL is brought into contact with the care solution and washed. Used by.

In the ophthalmic composition for nonionic SHCL of the present invention, the type of nonionic SHCL to be applied is not particularly limited, and all nonionic SHCL that are currently marketed or marketed in the future are applicable. Can be. Here, “nonionic” means that the content of ionic components in the contact lens material is less than 1 mol% in accordance with US FDA (US Food and Drug Administration) standards.

Further, in the ophthalmic composition for nonionic SHCL of the present invention, the water content of the nonionic SHCL to be applied is not particularly limited, and is, for example, 90% or less, preferably 60% or less, more preferably 50%. The following are mentioned. Since SHCL contains a hydrogel material, it contains at least more than 0% moisture. In particular, nonionic SHCL having a moisture content of 35% or less tends to have particularly strong adhesion to corneal epithelial cells. According to the ophthalmic composition for nonionic SHCL of the present invention, the effect of suppressing adhesion of corneal epithelial cells can be effectively exhibited even for nonionic SHCL having strong adhesion to corneal epithelial cells. In view of the corneal cell adhesion inhibitory effect of the present invention, the nonionic SHCL ophthalmic composition of the present invention includes nonionic SHCL having a moisture content of 35% or less as a suitable application target.

  Here, the moisture content of nonionic SHCL indicates the ratio of water in nonionic SHCL, and is specifically determined by the following calculation formula.

Moisture content (%) = (weight of hydrated water / weight of nonionic SHCL in hydrated state) x 100
Such moisture content can be measured by a gravimetric method according to the description of ISO18369-4: 2006.

  Since the ophthalmic composition for nonionic SHCL of the present invention can exhibit the action of accelerating the metabolism of eye cells and eliminating eye fatigue based on the components (A) and (B), It can be used for the purpose of improving fatigue eyes.

Conventionally, it has been known that wearing a hard contact lens made of polymethyl methacrylate (PMMA) material tends to cause corneal epithelial disorder (3 o'clock to 9 o'clock staining) due to adhesion of the lens to the cornea. ing. In addition, it is known that even when wearing SCL, a person who has symptoms such as dry eyes (for example, a dry eye patient) tends to damage the cornea due to the lens and tends to cause corneal staining. Nonionic SHCL, on the other hand, has the property of remarkably adhering to corneal epithelial cells, and moreover it is generally harder than normal non-silicone SCL as an inherent property of silicone hydrogel contact lenses, thus causing physical damage to the corneal epithelium. It tends to be easy. In view of the characteristics of such nonionic SHCL, it is apparent that the above-described corneal epithelial disorder is easily caused even by wearing nonionic SHCL. On the other hand, according to the ophthalmic composition for nonionic SHCL of the present invention, it is possible to effectively suppress adhesion of corneal epithelial cells to nonionic SHCL, so that the corneal epithelium caused by wearing nonionic SHCL Disability can be prevented. Therefore, the ophthalmic composition for nonionic SHCL of the present invention can be used as a preventive agent for corneal epithelial disorder caused by wearing nonionic SHCL, and particularly for those having symptoms of dry eyes (for example, dry For eye patients).

  In addition, since corneal epithelial cells also have a barrier function against allergens, corneal epithelial disorders caused by wearing nonionic SHCL as described above decrease the barrier function and cause allergic symptoms of the eye. There is a fear to make it easier. In contrast, according to the ophthalmic composition for nonionic SHCL of the present invention, corneal epithelial cells are maintained in a normal state by suppressing adhesion of corneal epithelial cells to nonionic SHCL. It is possible to maintain the barrier function of cells. Therefore, the ophthalmic composition for nonionic SHCL of the present invention is an ophthalmic disease preventive agent for a person who uses nonionic SHCL to enhance and prevent various eye diseases including allergic symptoms ( For example, it is suitably used as a prophylactic agent for allergic symptoms.

  In addition, the ophthalmic composition for nonionic SHCL of the present invention can effectively prevent corneal epithelial damage such as corneal staining caused by lipid adsorption to nonionic SHCL. Can also be used as a preventive agent for corneal epithelial disorders.

2. Method for inhibiting lipid adsorption to nonionic SHCL, and method for imparting action to inhibit lipid adsorption to nonionic SHCL As described above, by using the components (A) and (B) together, nonionic It is possible to suppress the adsorption of lipids to sex SHCL.

  Therefore, the present invention provides a composition containing (A) vitamin B6 and at least one selected from the group consisting of (B) vitamin E and vitamin A from a non-ionic viewpoint. Provided is a method for suppressing the adsorption of lipids to nonionic SHCL, which is characterized by contacting with non-ionic SHCL. Furthermore, the ophthalmic composition for nonionic SHCL is blended with (A) vitamin B6 and (B) at least one selected from the group consisting of vitamin E and vitamin A. The present invention also provides a method for imparting an action of suppressing lipid adsorption to nonionic SHCL to the ophthalmic composition.

  In these methods, the types and blending ratios of components (A) and (B), the types and blending ratios of other ingredients to be blended, the dosage form of the nonionic SHCL ophthalmic composition, and the nonionic properties to be applied. About the kind etc. of SHCL, it is the same as that of said "1. Ophthalmic composition for nonionic SHCL."

3. Method for inhibiting adhesion of corneal epithelial cells to nonionic SHCL, and method for imparting adhesion inhibiting action of corneal epithelial cells to nonionic SHCL As described above, by using the above components (A) and (B) together, Adhesion of corneal epithelial cells to ionic SHCL can be suppressed.

  Therefore, the present invention provides a composition containing (A) vitamin B6 and at least one selected from the group consisting of (B) vitamin E and vitamin A from a non-ionic viewpoint. Provided is a method for suppressing adhesion of corneal epithelial cells to nonionic SHCL, which comprises contacting with sexual SHCL. Furthermore, the ophthalmic composition for nonionic SHCL is blended with (A) vitamin B6 and (B) at least one selected from the group consisting of vitamin E and vitamin A. The present invention provides a method for imparting an adhesion suppressing action of corneal epithelial cells to nonionic SHCL to the ophthalmic composition.

  In these methods, the types and blending ratios of components (A) and (B), the types and blending ratios of other ingredients to be blended, the dosage form of the nonionic SHCL ophthalmic composition, and the nonionic properties to be applied. About the kind etc. of SHCL, it is the same as that of said "1. Ophthalmic composition for nonionic SHCL."

  EXAMPLES The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

Reference Test Example 1: Evaluation of lipid adsorbability of various SCLs The following experiments were conducted using the various soft contact lenses shown in Table 1, and the lipid adsorbability of the soft contact lenses was evaluated. The soft contact lenses used in this test are all commercially available products.

First, fluorescently labeled lipid (N- (fluorescein-5-thiocarbamoyl) -1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt; manufactured by invitrogen) 1 mg / mL
Prepared as a fluorescent lipid solution by adding physiological saline (0.9w / v% sodium chloride) to 500μL of a mixture of chloroform and methanol at a concentration ratio of 1: 4 in a volume ratio of 1: 4 to make a total volume of 20mL did. Each soft contact lens was immersed in physiological saline for overnight or longer and pre-tested. In the sample group, each SCL was immersed one by one in 1 mL of the fluorescent lipid solution in a 24-well microplate and shaken at 34 ° C. for 24 hours. Moreover, each soft contact lens was immersed one by one in physiological saline as a blank group, and the same shaking treatment as the sample group was performed. After 24 hours, each soft contact lens is transferred to a plate containing 1 mL of new physiological saline, and a fluorescent plate reader (manufactured by Thermo Fisher Scientific Inc.)
Was used to measure the fluorescence intensity of each well (excitation wavelength: 485 nm, fluorescence wavelength: 538 nm). A value obtained by subtracting the fluorescence intensity of the blank group from the fluorescence intensity of the sample group was calculated as an index of the amount of adsorbed lipid.

  The results are shown in FIG. As is clear from FIG. 1, the lenses A and B, which are nonionic SHCL, have a significantly higher lipid adsorption amount than the lenses C, which are ionic SHCL, and the lenses D to F, which are conventional hydrogel lenses. It was confirmed that the problem of lipid contamination was serious.

Test Example 1: Nonionic SHCL lipid adsorption inhibition evaluation (1)
Using the lens A of Reference Test Example 1 as nonionic SHCL, the effect of nonionic SHCL on lipid adsorption was examined for each test solution shown in Table 2 below.

First, fluorescently labeled lipid (N- (fluorescein-5-thiocarbamoyl) -1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt; manufactured by invitrogen) 1 mg / mL
Prepared as a fluorescent lipid solution by adding physiological saline (0.9w / v% sodium chloride) to 500μL of a mixture of chloroform and methanol at a concentration ratio of 1: 4 in a volume ratio of 1: 4 to make a total volume of 20mL did. Each soft contact lens was immersed in physiological saline for overnight or longer and pre-tested. Next, 1 mL of each test solution (Example 1-3 and Comparative Example 1-4) is placed in each well of a 24-well microplate, and the lens A that has undergone pre-test treatment is immersed therein one by one. The mixture was shaken at 24 ° C for 24 hours. Each lens after the shaking treatment was transferred to a 24-well microplate containing 1 mL of the fluorescent lipid solution and again shaken at 34 ° C. for 24 hours. Moreover, the lens A was immersed in 1 mL of physiological saline as a blank group one by one, and the same shaking treatment as that of the sample group was performed. After 24 hours, each lens A after shaking treatment was transferred to a plate containing 1 mL of fresh physiological saline, and the fluorescence intensity of each well was measured (excitation) using a fluorescence plate reader (Thermo Fisher Scientific Inc.). Wavelength: 485 nm, fluorescence wavelength: 538 nm
). The value obtained by subtracting the fluorescence intensity of the blank group from the fluorescence intensity of each sample group is obtained as an index of the amount of adsorbed lipid, and the amount of adsorbed lipid in each test solution when the amount of adsorbed lipid of the control (Comparative Example 1) is 100%. The relative value (%) was calculated.

  The result is shown in FIG. As shown in FIG. 2, when each of retinol palmitate, tocopherol acetate or pyridoxine hydrochloride (particularly tocopherol acetate or pyridoxine hydrochloride) is used alone, there is almost no lipid adsorption inhibitory effect compared to the control. It was recognized (Comparative Example 2-4). On the other hand, unexpectedly, it was shown that lipid adsorption to nonionic SHCL can be synergistically suppressed when retinol palmitate and pyridoxine hydrochloride, which are almost independent of each other, are used in combination. (Example 1). It was revealed that the same was observed in the combination of tocopherol acetate and pyridoxine hydrochloride that did not show any lipid adsorption inhibitory effect (Example 2). Furthermore, when these three components, retinol palmitate, tocopherol acetate, and pyridoxine hydrochloride were used in combination, a particularly remarkable lipid adsorption inhibitory effect was observed (Example 3).

Test Example 2: Nonionic SHCL lipid adsorption inhibition evaluation (2)
Using the lens A (nonionic SHCL) of Reference Test Example 1 above, the same method as in Test Example 1 was used to evaluate the lipid adsorption inhibitory effect on nonionic SHCL for each test solution shown in Table 3 below. .

The results are shown in FIG. 3 as relative values (%) of the amount of adsorbed lipid of each test solution when the amount of adsorbed lipid of the control (Comparative Example 5) is 100%. As shown in FIG. 3, when the blending concentrations and blending ratios of retinol palmitate, tocopherol acetate, and pyridoxine hydrochloride were varied, similar lipid adsorption to nonionic SHCL as in Test Example 1 above. It was confirmed that the inhibitory effect was exhibited (Example 4-6).

Reference Test Example 2: Evaluation of Adhesion of Corneal Epithelial Cells of Various SCLs The following experiment was conducted using five types of soft contact lenses shown in Table 4, and the corneal epithelial cell adhesion on the surface of the soft contact lenses was evaluated. The soft contact lenses used in this test are all commercially available products.

Specifically, it was evaluated by the following method. Each soft contact lens was immersed one by one in a 24-well microplate containing 900 μL of growth medium (DMEM medium containing 10% fetal bovine serum) so that the convex surface was on the top. Cell suspension (1 × 10 ⁵ cell / mL) of rabbit corneal epithelial cell line SIRC (ATCC number: CCL-60) prepared using growth medium in each well
100 μL each was seeded, cultured at 37 ° C. under 5% CO ₂ for 48 hours, and the number of viable cells attached to the soft contact lens was counted. As a control, cells were cultured on the bottom of the microplate without immersing any lens, and the number of viable cells in the wells was counted (control group). Note that Cell Counting Kit (manufactured by Dojindo Laboratories) was used for the measurement of the number of viable cells. The ratio of the number of viable cells adhering to the surface of each soft contact lens (ratio of the number of viable cells to the control group;%) was calculated with respect to the total number of viable cells contained in the wells of the control group.

The obtained results are shown in FIG. As is clear from FIG. 4, the lens 1 is nonionic SHCL.
2 and 2 were confirmed to have remarkable corneal epithelial cell adhesion as compared with the lens 3 that is ionic SHCL and the lens 4 or 5 that is a non-silicone hydrogel contact lens. Further, when the adhesion state of the cells to the soft contact lens was observed with a microscope, cell adhesion was hardly confirmed in the lenses 3, 4 and 5, but corneal epithelial cells were formed on the surfaces of the lenses 1 and 2. It was confirmed that they were adhered. From the above results, it was confirmed that nonionic SHCL has significantly higher adhesion of corneal epithelial cells than other types of lenses, and wearing nonionic SHCL has adverse effects such as damage to the corneal surface. It became clear that it could be given.

Test Example 3: Adhesion inhibition test of corneal epithelial cells to nonionic SHCL Using the test solution shown in Table 5, the adhesion inhibition effect of corneal epithelial cells to nonionic SHCL was evaluated.

The lens 2 (nonionic SHCL) shown in Table 4 is immersed one by one in 3 mL of each test solution shown in Table 5 (Examples 7-8 and Comparative Example 6-8) and allowed to stand at 34 ° C. for 24 hours. I put it. After the lens 2 taken out from each test solution is gently washed with physiological saline, the moisture is wiped off, and the convex surface is placed on a 24-well plate containing 900 μL of growth medium (DMEM medium containing 10% fetal bovine serum). One piece was immersed. Each well was seeded with 100 μL of a cell suspension (1 × 10 ⁵ cell / mL) of a rabbit corneal epithelial cell line SIRC (ATCC number: CCL-60) prepared using a growth medium, and the culture was performed at 37 ° C., 5 ° C. After culturing for 48 hours under% CO ₂ conditions, the number of viable cells adhered to the lens was counted (sample group). As a control, instead of each test solution, using a lens 2 immersed in the control test solution shown in Table 5, a cell suspension of a rabbit corneal epithelial cell line was seeded and cultured under the same conditions as described above. The number of viable cells adhered to the lens 2 was counted (control group). Furthermore, as a blank, a well was prepared by adding only 1000 μL of a growth medium (DMEM medium containing 10% fetal bovine serum) without seeding rabbit corneal epithelial cells, and 37 lenses 2 not subjected to immersion treatment were prepared. The mixture was allowed to stand for 48 hours under the conditions of 5 ° C. and 5% CO ₂ (blank group). For counting the number of viable cells, Cell Counting Kit (manufactured by Dojindo Laboratories)
The cell adhesion inhibition rate (%) was calculated according to the following formula.

The obtained results are shown in FIG. As is clear from FIG. 5, it was revealed that the corneal cell adhesion inhibition rate with respect to nonionic SHCL can be remarkably enhanced by using a specific combination of two or three components of the present invention.

Formulation Example In the formulation described in Table 6, non-ionic SHCL eye drops (Examples 9-13), non-ionic SHCL mounting solution (Example 14), non-ionic SHCL mounting solution and eye drops (Example 15) ), A nonionic SHCL eyewash (Example 16), and a nonionic SHCL cleaning solution (Examples 17-18).

Claims (10)

  (A) at least one vitamin B6 selected from the group consisting of pyridoxine, pyridoxal, pyridoxamine, and salts thereof; and (B) tocopherol, tocotrienol, tocopherol acetate, tocopherol succinate, tocopherol nicotinate, and tocopherol linolenate And at least one vitamin E selected from the group consisting of these salts, and retinol (vitamin A1), 3-dehydroretinol (vitamin A2), retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, Retinol octylate, retinol laurate, retinol oleate, retinol linolenate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoic acid, δ-to Containing at least one selected from the group consisting of at least one vitamin A selected from the group consisting of ferryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, and salts thereof An ophthalmic composition for nonionic silicone hydrogel contact lenses.   The ophthalmic composition for nonionic silicone hydrogel contact lenses according to claim 1, wherein the total amount of component (B) is 0.2 to 2500 parts by weight per 100 parts by weight of total amount of component (A). The ophthalmic composition for nonionic silicone hydrogel contact lenses according to claim 1 or 2, having a pH of 4.0 to 9.5. The ophthalmic composition for nonionic silicone hydrogel contact lenses according to any one of claims 1 to 3 , which is an eye drop.   The ophthalmic composition comprises (A) at least one vitamin B6 selected from the group consisting of pyridoxine, pyridoxal, pyridoxamine, and salts thereof, and (B) tocopherol, tocotrienol, tocopherol acetate, tocopherol succinate, nicotinic acid At least one vitamin E selected from the group consisting of tocopherol, tocopherol linolenate, and salts thereof, and retinol (vitamin A1), 3-dehydroretinol (vitamin A2), retinol palmitate, retinol acetate, retinol butyrate , Retinol propionate, Retinol octylate, Retinol laurate, Retinol oleate, Retinol linolenate, Retinal, Retinoic acid, Methyl retinoic acid, Ethyl retinoic acid, Retinoic acid And at least one selected from the group consisting of at least one vitamin A selected from the group consisting of salts, δ-tocopheryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, and salts thereof The method to provide the said ophthalmic composition with the effect | action which suppresses adsorption | suction of the lipid to a nonionic silicone hydrogel contact lens including mix | blending 1 type.   The ophthalmic composition comprises (A) at least one vitamin B6 selected from the group consisting of pyridoxine, pyridoxal, pyridoxamine, and salts thereof, and (B) tocopherol, tocotrienol, tocopherol acetate, tocopherol succinate, nicotinic acid At least one vitamin E selected from the group consisting of tocopherol, tocopherol linolenate, and salts thereof, and retinol (vitamin A1), 3-dehydroretinol (vitamin A2), retinol palmitate, retinol acetate, retinol butyrate , Retinol propionate, Retinol octylate, Retinol laurate, Retinol oleate, Retinol linolenate, Retinal, Retinoic acid, Methyl retinoic acid, Ethyl retinoic acid, Retinoic acid And at least one selected from the group consisting of at least one vitamin A selected from the group consisting of salts, δ-tocopheryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, and salts thereof A method of imparting to the ophthalmic composition an inhibitory effect on adhesion of corneal epithelial cells to a nonionic silicone hydrogel contact lens, comprising blending with one kind.   (A) at least one vitamin B6 selected from the group consisting of pyridoxine, pyridoxal, pyridoxamine, and salts thereof; and (B) tocopherol, tocotrienol, tocopherol acetate, tocopherol succinate, tocopherol nicotinate, and tocopherol linolenate And at least one vitamin E selected from the group consisting of these salts, and retinol (vitamin A1), 3-dehydroretinol (vitamin A2), retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, Retinol octylate, retinol laurate, retinol oleate, retinol linolenate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoic acid, δ-to Containing at least one selected from the group consisting of at least one vitamin A selected from the group consisting of ferryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, and salts thereof A lipid adsorption inhibitor for a nonionic silicone hydrogel contact lens comprising an ophthalmic composition.   (A) at least one vitamin B6 selected from the group consisting of pyridoxine, pyridoxal, pyridoxamine, and salts thereof; and (B) tocopherol, tocotrienol, tocopherol acetate, tocopherol succinate, tocopherol nicotinate, and tocopherol linolenate And at least one vitamin E selected from the group consisting of these salts, and retinol (vitamin A1), 3-dehydroretinol (vitamin A2), retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, Retinol octylate, retinol laurate, retinol oleate, retinol linolenate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoic acid, δ-to Containing at least one selected from the group consisting of at least one vitamin A selected from the group consisting of ferryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, and salts thereof An inhibitor of corneal epithelial cell adhesion to a nonionic silicone hydrogel contact lens, comprising an ophthalmic composition.   An eye discomfort suppressant comprising an ophthalmic composition applied to a nonionic silicone hydrogel contact lens, wherein the ophthalmic composition is selected from the group consisting of (A) pyridoxine, pyridoxal, pyridoxamine, and salts thereof And at least one vitamin B selected from the group consisting of (B) tocopherol, tocotrienol, tocopherol acetate, tocopherol succinate, tocopherol nicotinate, tocopherol linolenate, and salts thereof. And retinol (vitamin A1), 3-dehydroretinol (vitamin A2), retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, retinol octylate, retinol laurate, retinol oleate, From the group consisting of retinol nolenate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, δ-tocopheryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, and salts thereof An eye discomfort suppressant containing at least one selected from the group consisting of at least one selected from vitamin A.   A haze suppression agent comprising an ophthalmic composition applied to a nonionic silicone hydrogel contact lens, wherein the ophthalmic composition is selected from the group consisting of (A) pyridoxine, pyridoxal, pyridoxamine, and salts thereof. And at least one vitamin B selected from the group consisting of (B) tocopherol, tocotrienol, tocopherol acetate, tocopherol succinate, tocopherol nicotinate, tocopherol linolenate, and salts thereof. And retinol (vitamin A1), 3-dehydroretinol (vitamin A2), retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, retinol octylate, retinol laurate, retinol oleate, From the group consisting of retinol nolenate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, δ-tocopheryl retinoate, α-tocopheryl retinoate, β-tocopheryl retinoate, and salts thereof A haze suppression agent containing at least one selected from the group consisting of at least one selected from vitamin A.

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