Ophthalmic composition for silicone hydrogel contact lens

Abstract

To provide an ophthalmic composition for a silicone hydrogel contact lens (SHCL) which suppresses lipid adsorption to the surface of a nonionic SHCL surface and also suppresses accumulation of pollen protein to the ionic SHCL.SOLUTION: There is prepared an ophthalmic composition for a silicone hydrogel contact lens by combination of (A) at least one selected from the group consisting of flavine adenine dinucleotide, pyridoxine and a salt thereof and (B) at least one selected from the group consisting of chondroitin sulfate, aminoethylsulfonic acid, aspartic acid and a salt thereof.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an ophthalmic composition for silicone hydrogel contact lenses. In order to prevent lipid adsorption onto non-ionic silicone hydrogel contact lenses, The accumulation of pollen proteins in ionic silicone hydrogel contact lenses was also confirmed. The present invention relates to an ophthalmic composition for silicone hydrogel contact lenses that can suppress the accumulation of In addition, the present invention suppresses lipid adsorption onto nonionic silicone hydrogel contact lenses. US201002233633A1 - Method for applying pollen proteins to ionic silicone hydrogel contact lenses - Google Patents The present invention also relates to a method for inhibiting the accumulation of nonionic silicone hydrogel copolymers. The present invention relates to a method for inhibiting adhesion of corneal cells to the surface of a contact lens. [Background technology]

[0002] In recent years, the number of contact lens (CL) wearers has increased, especially soft contact lenses. The number of people wearing soft contact lenses (SCLs) is increasing. In general, when wearing soft contact lenses, In the early stages of corneal hyperplasia, the amount of oxygen supplied from the atmosphere decreases, resulting in inhibition of corneal epithelial cell division and corneal hyperplasia. It has been pointed out that this can lead to a thicker membrane. Soft contact lenses have been developed.

[0003] Silicone hydrogel contact lenses have high oxygen permeability under such circumstances. Silicone hydrogels are soft contact lenses that have been developed in recent years. Gel contact lenses are made by blending silicone with hydrogel, which is a new type of contact lens that is more flexible than conventional hydrogel lenses. The oxygen permeability is several times higher than that of hydrogel contact lenses. This improves the oxygen supply shortage, which is a weakness of lenses, and reduces the adverse effects on the cornea caused by oxygen deficiency. It is expected to significantly reduce acoustic noise.

[0004] On the other hand, silicone hydrogel contact lenses are different from conventional hydrogel contact lenses. It has been pointed out that compared with men, they are more susceptible to lipid stains from the tear film and cosmetics. Such lipid stains can cause the lenses to become cloudy, which is uncomfortable for the wearer. This gives a sense of pleasure and impairs the quality of life. Dirt on lenses can adversely affect the vision correction power of the lenses. In recent years, such lipid stains on contact lenses have come to be called corneal staining. It has also been pointed out that it may affect the development of corneal epithelial disorders.

[0005] In general, ophthalmic compositions used for contact lenses are It is essential to design the facility with due consideration given to safety and other factors depending on the type of facility. In particular, Soft contact lenses vary in terms of their ionic nature and water content depending on the material. Therefore, the ophthalmic composition used in the soft contact lens is It is essential to design the formulation according to the characteristics of the lens.

[0006] Hay fever is caused by the pollen proteins that act as antigens and come into contact with mucous membranes. In recent years, the number of hay fever patients has been increasing. In the field of ophthalmology, ophthalmic compositions that are useful for preventing and suppressing the worsening of hay fever are being developed. There is a strong demand for development of

[0007] On the other hand, flavin adenine dinucleotide, pyridoxine, chondroitin sulfate, amino Ethylsulfonic acid, aspartic acid, and their salts promote energy metabolism. , promotes metabolism and cellular respiration, relieves eye fatigue, and replenishes tear fluid. However, these ingredients have been used in ophthalmic compositions for the following reasons: The effect on corn hydrogel contact lenses has not been elucidated. The combination of certain ingredients among these is the key to silicone hydrogel contact lenses. At present, it is not even possible to make any inference about the impact this will have on the enterprises. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Hiroshi Shioya, New Ophthalmology Vol. 25, No. 7, pp. 907-912, 2008 Summary of the Invention [Problem to be solved by the invention]

[0009] The present inventors have conducted various studies on the lipid adsorption properties of various soft contact lenses. However, non-ionic silicone hydrogel contact lenses (hereinafter referred to as non-ionic SHC L) is one of the soft contact lenses that is most susceptible to absorbing lipids. This significant amount of lipid contamination can cause the lenses to become cloudy and cause wearers to feel uncomfortable. This may impair your quality of life and may also adversely affect the vision correction power of the lenses. Furthermore, such lipid stains may cause corneal epithelial disorders such as corneal staining. Therefore, by suppressing lipid adsorption to non-ionic SHCL, the fogging of lenses can be prevented. This prevents the lens from becoming worn, improves the wearing comfort, and maintains the lens's original vision correction power. A method for preventing injury and enabling the comfortable and safe use of non-ionic SHCL Development is required.

[0010] Furthermore, the present inventors have investigated the adsorption characteristics of pollen proteins to various soft contact lenses. While conducting various studies on the properties of ionic silicone hydrogel contact lenses, (hereinafter, referred to as ionic SHCL) has a high adsorption rate of pollen proteins. In general, proteins are easily absorbed into silicone hydrogels. It is thought that it is difficult for the material to adhere to the corneal graft lens (hereinafter, sometimes referred to as SHCL). This finding was completely unexpected. As a result, the cleaning effect of tears is reduced, and foreign objects such as pollen get into the eyes. It is believed that the risk of developing hay fever increases because the pollen becomes more easily retained. If a large amount of pollen proteins are adsorbed and accumulated on the tact lens, the risk of developing hay fever may increase. This will significantly increase the risk of developing allergic reactions. If the removal of pollen proteins adsorbed on contact lenses becomes insufficient, the contact lenses This can lead to discomfort and shorten the period of use. There is also a need to develop methods to suppress the accumulation of pollen proteins in ionic SHCL. is.

[0011] Therefore, one of the objects of the present invention is to develop an SHC that can suppress lipid adsorption to nonionic SHCL. Another object of the present invention is to provide an ophthalmic composition for use in an ophthalmic liquid crystal display. By promoting the removal of pollen proteins from CL and preventing their reattachment, ionic SHCL The object of the present invention is to provide an ophthalmic composition for SHCL that can suppress the accumulation of pollen proteins in the eyes. [Means for solving the problem]

[0012] As a result of intensive research to solve the above problems, the present inventors have discovered that (A) flavin adenine At least one member selected from the group consisting of dinucleotides, pyridoxine, and salts thereof and (B) chondroitin sulfate, aminoethylsulfonic acid, aspartic acid, and By using at least one selected from the group consisting of nonionic SH salts, The inventors have also found that the lipid adsorption to CL can be significantly suppressed synergistically. The combined use of the above components (A) and (B) inhibits the accumulation of pollen proteins in ionic SHCL. Furthermore, the present inventors have found that the above-mentioned components (A) and (B) can be suppressed. It was also found that the combined use of α- and β-blockers significantly inhibited the adhesion of corneal epithelial cells to non-ionic SHCL. The present invention was completed through further improvements based on this knowledge. do.

[0013] That is, the present invention provides the following ophthalmic compositions for SHCL. Item 1-1. (A) Flavin adenine dinucleotide, pyridoxine, and their salts (B) at least one selected from the group consisting of chondroitin sulfate, aminoethyl At least one selected from the group consisting of sulfonic acid, aspartic acid, and salts thereof An ophthalmic composition for silicone hydrogel contact lenses comprising: Item 1-2. (A) Ingredients include sodium flavin adenine dinucleotide and hydrochloric acid The silico compound according to item 1-1, which contains at least one selected from the group consisting of pyridoxine. Ophthalmic composition for use in hydrogel contact lenses. Item 1-3. Item 1-1 or Item 1-2, which contains 0.001 to 1.0 w / v% of component (A) in total. 1-2. An ophthalmic composition for silicone hydrogel contact lenses. Item 1-4. (B) Ingredients include sodium chondroitin sulfate, aminoethyl sulfate Aspartic acid, potassium aspartate, magnesium aspartate, and magnesium aspartate Items 1-1 to 1-3, which contain at least one selected from the group consisting of nesium and potassium 10. An ophthalmic composition for silicone hydrogel contact lenses according to any one of claims 1 to 9. Item 1-5. (B) Contains a total amount of 0.001 to 5.0 w / v% of the component, Items 1-1 to 1 10. An ophthalmic composition for silicone hydrogel contact lenses according to any one of claims 1 to 4. Item 1-6. The silicone composition according to any one of Items 1-1 to 1-5, further comprising a buffer. Ophthalmic composition for hydrogel contact lenses. Item 1-7. The silicone hydrogel according to item 1-6, which contains a borate buffer as a buffer. Ophthalmic compositions for gel contact lenses. Item 1-8. The total amount of the buffer is 0.01 to 10 w / v%. Item 1-6 or 1-7. The ophthalmic composition for use with silicone hydrogel contact lenses described above. Item 1-9. The silicone composition according to any one of items 1-1 to 1-8, further comprising an isotonicity agent. Ophthalmic composition for use in hydrogel contact lenses. Item 1-10. Isotonicity agents include sodium chloride, potassium chloride, calcium chloride, salt At least one selected from the group consisting of magnesium chloride, glycerin, and propylene glycol. The ophthalmic composition for silicone hydrogel contact lenses according to items 1-9, which contains at least one of the above. Composition. Item 1-11. The isotonicity agent is contained in a total amount of 0.01 to 10 w / v %. Item 1-9 or 1- 11. An ophthalmic composition for silicone hydrogel contact lenses according to claim 10. Item 1-12. The silicone hybrid according to any one of Items 1-1 to 1-11, which is an eye drop. Ophthalmic composition for hydrogel contact lenses. Item 1-13. For non-ionic silicone hydrogel contact lenses, Item 1- The ophthalmic composition for silicone hydrogel contact lens according to any one of 1 to 1-12. . Item 1-14. For ionic silicone hydrogel contact lenses, Item 1-1 13. An ophthalmic composition for silicone hydrogel contact lenses according to any one of 1 to 12.

[0014] The present invention also relates to the following nonionic silicone hydrogel contact lenses. The present invention provides a method for inhibiting lipid adsorption. Item 2. (A) Flavin adenine dinucleotide, pyridoxine and their salts and (B) at least one selected from the group consisting of chondroitin sulfate, aminoethyl sulfide, and at least one selected from the group consisting of carboxylic acid, aspartic acid, and salts thereof. An ophthalmic composition for silicone hydrogel contact lenses comprising a non-ionic silicone A non-ionic silicone hydrogel contact lens is contacted with the non-ionic silicone hydrogel contact lens. A method for inhibiting lipid adsorption onto hydrogel contact lenses.

[0015] The present invention also provides an ophthalmic composition for SHCL, which comprises a lipid for nonionic SHCL. A method for imparting an effect of suppressing adsorption is provided. Item 3. An ophthalmic composition for silicone hydrogel contact lenses, comprising (A) flavin a At least one selected from the group consisting of denine dinucleotide, pyridoxine and salts thereof (B) chondroitin sulfate, aminoethylsulfonic acid, aspartic acid, and The present invention relates to a method for producing a schizophrenia-based composition comprising the steps of: Nonionic silicone hydrogel in ophthalmic composition for ricone hydrogel contact lenses A method for imparting an effect of suppressing lipid adsorption to a contact lens.

[0016] The present invention also provides a method for suppressing the accumulation of pollen proteins in the ionic SHCLs described below. A method is provided. Item 4. (A) Flavin adenine dinucleotide, pyridoxine and their salts and (B) at least one selected from the group consisting of chondroitin sulfate, aminoethyl sulfide, and at least one selected from the group consisting of carboxylic acid, aspartic acid, and salts thereof. The ophthalmic composition for silicone hydrogel contact lenses having an ionic silicone hydrogel is The present invention relates to an ionic silicone hydrogel contact lens. A method for inhibiting the accumulation of pollen proteins on a rogel contact lens.

[0017] The present invention also relates to an ophthalmic composition for SHCL, comprising the following: The present invention provides a method for imparting an effect of inhibiting protein accumulation. Item 5. An ophthalmic composition for silicone hydrogel contact lenses, comprising (A) flavin a At least one selected from the group consisting of denine dinucleotide, pyridoxine and salts thereof (B) chondroitin sulfate, aminoethylsulfonic acid, aspartic acid, and The present invention is characterized in that at least one selected from the group consisting of these salts is blended. Inhibits the accumulation of pollen proteins on hydrophilic silicone hydrogel contact lenses A method of applying a composition to the ophthalmic composition.

[0018] The present invention also provides a method for inhibiting adhesion of corneal epithelial cells to nonionic SHCL as described below. Provide the law. Item 6. (A) Flavin adenine dinucleotide, pyridoxine and their salts and (B) at least one selected from the group consisting of chondroitin sulfate, aminoethyl sulfide, and at least one selected from the group consisting of carboxylic acid, aspartic acid, and salts thereof. An ophthalmic composition for silicone hydrogel contact lenses comprising a non-ionic silicone A non-ionic silicone hydrogel contact lens is contacted with the non-ionic silicone hydrogel contact lens. A method for inhibiting adhesion of corneal epithelial cells to hydrogel contact lenses.

[0019] The present invention also relates to an ophthalmic composition for SHCL, which is described below, and which has a function of preventing the formation of non-ionic SHCL. A method for imparting an inhibitory effect on adhesion of corneal epithelial cells is provided. Item 7. An ophthalmic composition for silicone hydrogel contact lenses, comprising (A) flavin a At least one selected from the group consisting of denine dinucleotide, pyridoxine and salts thereof (B) chondroitin sulfate, aminoethylsulfonic acid, aspartic acid, and The present invention relates to a method for producing a schizophrenia-based composition comprising the steps of: Nonionic silicone hydrogel in ophthalmic composition for ricone hydrogel contact lenses A method for imparting an inhibitory effect on adhesion of corneal epithelial cells to contact lenses. Effect of the Invention

[0020] The ophthalmic composition for SHCL of the present invention significantly suppresses lipid adsorption to non-ionic SHCL. Therefore, according to the ophthalmic composition for SHCL of the present invention, the non-ionic SHCL Prevents lipid stains and prevents clouding of non-ionic SHCL and non-ionic SHC L The original visual acuity correction power can be maintained, and furthermore, lipid adsorption to non-ionic SHCL It effectively prevents corneal staining and other corneal epithelial disorders caused by contact lenses, and provides comfortable and safe contact lenses. This allows the use of entirely non-ionic SHCL.

[0021] Furthermore, the ophthalmic composition for SHCL of the present invention prevents pollen tanning during wearing of ionic SHCL. Even when the protein comes into contact with ionic SHCL, the removal of pollen proteins from ionic SHCL is not observed. By promoting the adhesion of pollen and preventing reattachment, the accumulation of pollen proteins on ionic SHCL is suppressed. Therefore, the ophthalmic composition for SHCL of the present invention can be used for people with hay fever or those at risk of having hay fever. The risk of developing allergic symptoms can be reduced for the user. According to the ophthalmic composition for HCL, ionic SHC It also helps keep L clean.

[0022] In addition, non-ionic SHCL has the unique property of allowing corneal cells to adhere remarkably easily. This has been clarified by the research of the present inventors, but the ophthalmic composition for SHCL of the present invention Therefore, the adhesion of corneal cells to non-ionic SHCL can be effectively suppressed. Contact lenses have high epithelial cell adhesion, which can cause corneal cells to adhere to the lens while wearing the contact lenses. The cells are removed from the eye tissue each time the lens moves over the cornea or when the lens is removed. This can cause damage to the corneal surface and associated pain, which can lead to contact Significantly reducing the quality of life (QOL) of contact lens users. Therefore, the ophthalmic composition for SHCL of the present invention has an excellent anti-inflammatory effect on non-ionic SHCL. Non-ionic SHCL can be used safely because it can suppress adhesion of membrane cells. This makes it possible to wear the lenses continuously for long periods of time.

[0023] Thus, the ophthalmic composition for SHCL of the present invention is a composition containing nonionic and ionic SHCL. This solves all the problems that may be of concern when using SHCL, making it highly safe and reliable. Comfort can be ensured. [Brief description of the drawings]

[0024] [Figure 1] FIG. 2 is a graph showing the results of evaluation of lipid adsorption properties of various soft contact lenses in Reference Test Example 1. [Diagram 2] FIG. 1 shows the results of evaluating the effects of test solutions (Examples 1-3 and Comparative Examples 1-5) on the adsorption of lipids to nonionic SHCL in Test Example 1. [Diagram 3] FIG. 1 shows the results of evaluating the effects of test solutions (Examples 4-6 and Comparative Examples 1, 3-6) on the adsorption of lipids to nonionic SHCL in Test Example 2. [Figure 4] FIG. 1 shows the results of evaluation of the adhesiveness of corneal epithelial cells to various soft contact lenses in Reference Test Example 2. [Diagram 5]FIG. 13 is a graph showing the results of evaluating the inhibitory effect of test solutions (Example 1 and Comparative Examples 2-3) on corneal epithelial cell adhesion to nonionic SHCL in Test Example 3. [Figure 6] FIG. 13 is a graph showing the results of evaluating the inhibitory effect of test solutions (Examples 7-8) on corneal epithelial cell adhesion to nonionic SHCL in Test Example 4. [Figure 7] FIG. 13 is a graph showing the results of evaluating the effect of test solutions (Examples 9-10) on inhibiting adhesion of corneal epithelial cells to nonionic SHCL in Test Example 5. [Figure 8] FIG. 13 is a diagram showing the results of evaluating the adsorption of pollen proteins to various soft contact lenses in Reference Test Example 3. [Figure 9] FIG. 13 shows the results of evaluating the effect of test solutions (Example 1 and Comparative Examples 2-3) in removing pollen proteins adsorbed to ionic SHCL in Test Example 6. [Figure 10] FIG. 13 shows the results of evaluating the effect of test solutions (Examples 4 and 6, and Comparative Examples 3, 5, and 6) in removing pollen proteins adsorbed to ionic SHCL in Test Example 7. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] 1. Ophthalmic composition for SHCL The ophthalmic composition for SHCL of the present invention contains flavin adenine dinucleotide, pyridoxine and and salts thereof (hereinafter referred to as component (A)). It contains the compound .

[0026] (A) Flavin adenine dinucleotide is known as a coenzyme type vitamin B2. It is a compound of knowledge.

[0027] In addition, the salts of flavin adenine dinucleotide are medicinally and pharmacologically (pharmaceutical) There are no particular limitations as long as it is physiologically acceptable. Specific examples of the salts of leutidine include organic acid salts (e.g., lactate, acetate, butyrate, trifluoroacetate, etc.). Acetate, fumarate, maleate, tartrate, citrate, succinate, malonate salts, methanesulfonates, toluenesulfonates, tosylates, palmitates, stearylates, phosphates, etc.); inorganic acid salts (e.g., hydrochlorides, sulfates, nitrates, hydrobromides, phosphates etc.); salts with organic bases (e.g., methylamine, triethylamine, triethanolamine, etc.); Organic compounds such as amines, morpholines, piperazines, pyrrolidines, amino acids, tripyridines, and picolines. salts with amines, etc.); salts with inorganic bases [alkali metal salts (e.g., sodium salts, potassium salts, etc. salts, etc.); alkaline earth metal salts (e.g., calcium salts, magnesium salts, etc.); other gold These flavin adenine dinucleotides include flavin adenine dinucleotides such as flavin adenine dinucleotides, ... Among these salts, salts with inorganic bases and / or salts with organic bases are preferred, and salts with inorganic bases and / or salts with organic bases are more preferred. Preferably, it is a salt with an inorganic base, more preferably an alkali metal salt, and particularly preferably a sodium salt. These salts of flavin adenine dinucleotide can be used alone. Alternatively, any combination of two or more of them may be used.

[0028] Flavin adenine dinucleotide and its salts are the most effective for lipid absorption by non-ionic SHCL. Further enhance the adhesion inhibitory effect or inhibit the accumulation of pollen proteins in ionic SHCL. From the viewpoint of further enhancing the activity, a salt of flavin adenine dinucleotide is preferable, and a salt of flavin adenine dinucleotide is more preferable. or salts with inorganic bases and / or salts with organic bases, more preferably salts with inorganic bases, further More preferably, it is an alkali metal salt, and particularly preferably, it is a sodium salt (flavin adenine dinucleotide). The preferred examples of flavin adenine are as follows: The salts of dinucleotides have an inhibitory effect on the adhesion of corneal epithelial cells to non-ionic SHCL. This is also preferable from the viewpoint of increasing the layer height.

[0029] In addition, pyridoxine, one of the components in (A), is a water-soluble vitamin known as vitamin B6. It is a compound.

[0030] In addition, the salt of pyridoxine is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable. As the salt of pyridoxine, there is no particular limitation as long as it is compatible with the above-mentioned. , lactate, acetate, butyrate, trifluoroacetate, fumarate, maleate, tartrate , citrate, succinate, malonate, methanesulfonate, toluenesulfonate, tosylates, palmitates, stearates, etc.); inorganic acid salts (e.g., hydrochlorides, sulfates Among these pyridoxine salts, the most common are pyridoxine salts (nitrates, hydrobromides, phosphates, etc.). Among them, inorganic acid salts are preferred, and hydrochloride (pyridoxine hydrochloride) is more preferred. These pyridoxine salts may be used alone or in combination of two or more. They may be used in any combination.

[0031] Among pyridoxine and its salts, it has an even stronger effect of inhibiting lipid adsorption to non-ionic SHCL. or to further enhance the inhibitory effect of pollen protein accumulation on ionic SHCL. From this viewpoint, pyridoxine and its inorganic acid salts are preferred, and pyridoxine hydrochloride is more preferred. The pyridoxine and its salts exemplified as preferred herein are non-ionic. It is also suitable from the viewpoint of further enhancing the inhibitory effect of corneal epithelial cells on adhesion to SHCL. .

[0032] In the ophthalmic composition for SHCL of the present invention, the component (A) is a flavin adenine dinucleotide. One of the following may be used alone: ​​pyridoxine, pyridoxine, or a salt thereof. The preferred components of the component (A) used in the present invention are Suitable examples include sodium flavin adenine dinucleotide and pyridoxine hydrochloride. Can be obtained.

[0033] In the ophthalmic composition for SHCL of the present invention, the blending ratio of the component (A) is determined by the type of the component (A). The ratio is appropriately set depending on the type of the (B) component to be used in combination. For example, The total amount of the component (A) is 0.001 to 1.0 w / v%, preferably 0.001 to 1.0 w / v%, based on the total amount of the composition. More specifically, the total amount of the ophthalmic composition for SHCL is, for example, 0.01 to 0.2 w / v %. The blending ratio of each of the (A) components is, for example, within the following ranges. When component (A) is flavin adenine dinucleotide and / or a salt thereof: These are the total amounts The concentration is usually 0.001 to 1.0 w / v%, preferably 0.005 to 0.5 w / v%, and more preferably Or 0.01~0.1w / v%; When component (A) is pyridoxine and / or its salt: These are the total amounts, usually 0.001~ 1.0 w / v%, preferably 0.01 to 0.5 w / v%, and more preferably 0.02 to 0. 2 w / v%.

[0034] The ophthalmic composition for SHCL of the present invention contains, in addition to the above-mentioned component (A), chondroitin sulfate, acetylcholine, At least one selected from the group consisting of aminoethylsulfonic acid, aspartic acid, and salts thereof. In this way, (A) and (B) are contained in at least one of the above-mentioned substances. The combined use of components (A) and (B) effectively adsorbs lipids to nonionic SHCL. It is possible to suppress the accumulation of pollen proteins in ionic SHCL. In addition, the combined use of components (A) and (B) is a non-ionic SHC It also makes it possible to effectively inhibit adhesion of corneal epithelial cells to L.

[0035] (B) Of the components, chondroitin sulfate is a mixture of D-glucuronic acid and N-acetyl-D-galactosyltransferase. Glycosaminoglycan with a structure in which sulfate is bound to a sugar chain consisting of two repeating sugar units of ctosamine. Chondroitin sulfate and its salts are known chemicals that are known to have corneal protection effects, etc. It can be produced by known methods or is available commercially.

[0036] The chondroitin sulfate used in the present invention is medicinally, pharmacologically (pharmaceutical) or As long as it is physiologically acceptable, its origin is not particularly limited, and it may be, for example, a mammal or Those derived from fish cartilage (salmon cartilage, etc.) can be used. There are no particular limitations on the type of compound, so long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable. For example, the viscosity average molecular weight is from 1,000 to 100,000, preferably from 5,000 to 70,000, and more preferably The viscosity average molecular weight is about 1,000 to 50,000. Pharmacopoeia General Test Method Viscosity Measurement Method 1: Calculate the limiting viscosity η according to the capillary viscometer method ( Measurement conditions: Dissolving solution 0.2 mol / L NaCl, temperature 25.0 ± 0°C, Ubbelohde viscometer ) is calculated from the obtained intrinsic viscosity η according to the following formula I. Formula I: [η] = 5.8 × 10 -4 M 0.74 (Here, M is the viscosity average molecular weight. )

[0037] In addition, the salts of chondroitin sulfate are medicinally, pharmacologically (pharmaceutical) or physiologically There are no particular limitations to the amount of chondroitin sulfate, as long as it is acceptable to the patient. Specifically, examples of the salt include salts with organic bases (e.g., methylamine, triethylamine, triethylamine, etc.). Triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc. salts with organic amines, etc.), salts with inorganic bases [e.g., ammonium salts; alkali metal (na thorium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), aluminum Among these salts, preferred are salts with A salt of chondroitin sulfate with an inorganic base, more preferably an alkali metal salt, and even more preferably The sodium salt (sodium chondroitin sulfate) of these chondroitin sulfates The salts may be used alone or in any combination of two or more.

[0038] Chondroitin sulfate and its salts have the effect of inhibiting lipid adsorption to non-ionic SHCL. or further enhance the inhibitory effect of pollen protein accumulation in ionic SHCL. From this viewpoint, a salt of chondroitin sulfate is preferred, and chondroitin sulfate is more preferred. salts with inorganic bases, more preferably alkali metal salts of chondroitin sulfate, particularly preferably Examples of preferred chondroitin sulfate include sodium chondroitin sulfate. Droitin sulfate salts further suppressed the adhesion of corneal epithelial cells to non-ionic SHCL. It is also preferable from the viewpoint of increasing

[0039] In addition, among the components (B), aminoethylsulfonic acid is a known compound also known as taurine. It is an object.

[0040] Salts of aminoethylsulfonic acid include those which are medicinally, pharmacologically (pharmaceutical) or physiologically There are no particular limitations as long as it is acceptable. Specific examples of salts of aminoethylsulfonic acid include Typically, salts with organic bases (e.g., methylamine, triethylamine, triethanolamine, etc.) and organic amines such as amine, morpholine, piperazine, pyrrolidine, tripyridine, and picoline. salts of inorganic bases [e.g., ammonium salts; alkali metal (sodium, potassium) salts] Metals such as aluminum, alkaline earth metals (calcium, magnesium, etc.), and aluminum These aminoethylsulfonic acid salts may be used alone. Alternatively, any combination of two or more of them may be used.

[0041] Among aminoethylsulfonic acid and its salts, the lipid adsorption inhibitory effect on non-ionic SHCL is or to further enhance the inhibitory effect of pollen protein accumulation on ionic SHCL. From the viewpoint of the above, aminoethylsulfonic acid is preferred. As an example, aminoethylsulfonic acid acts on non-ionic SHCL and corneal epithelial cells. This is also preferable from the viewpoint of further enhancing the adhesion suppressing effect.

[0042] In addition, among the components (B), aspartic acid is an acidic acid also known as 2-aminobutanedioic acid. Aspartic acid is a compound known as aspartic acid. Aspartic acid can be L-, D-, or DL-form. However, the L-form is preferred.

[0043] Aspartic acid salts include those that are medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable. As a salt of aspartic acid, there is no particular limitation as long as it is a salt of aspartic acid. Examples of the salts include those having the same form as the salts that aminoethylsulfonic acid can take. Preferably, salts of aspartic acid with inorganic bases, more preferably alkali metal salts and alkali salts. Potassium earth metal salts, more preferably potassium aspartate and magnesium aspartate , and magnesium potassium aspartate, particularly preferably potassium aspartate These salts of aspartic acid may be used alone or in any combination of two or more. They may be used in any combination.

[0044] Aspartic acid and its salts have a stronger inhibitory effect on lipid adsorption to non-ionic SHCL. or further enhance the inhibitory effect of pollen protein accumulation on ionic SHCL. From the viewpoint of the present invention, it is preferable to use a salt of aspartic acid with an inorganic base, more preferably aspartic acid. Alkali metal salts and alkaline earth metal salts of the above, more preferably potassium aspartate, Magnesium aspartate and magnesium potassium aspartate are particularly preferred. Asparagine is preferably used as an example of asparagine. The ionic acid and its salts further enhanced the adhesion inhibitory effect of corneal epithelial cells to nonionic SHCL. It is also preferable from this viewpoint.

[0045] In the ophthalmic composition for SHCL of the present invention, the component (B) is chondroitin sulfate, amino Ethyl sulfonic acid, aspartic acid, and one of their salts are used alone. In the present invention, two or more kinds of the above-mentioned compounds may be used in combination. Suitable examples of the component (B) include sodium chondroitin sulfate and aminoethyl sulfate. Aspartic acid, potassium aspartate, magnesium aspartate, and magnesium aspartate Examples include potassium and potassium.

[0046] Among the components (B) used in the present invention, the component (B) that has the effect of inhibiting lipid adsorption to nonionic SHCL is From the viewpoint of further enhancing the above-mentioned properties, chondroitin sulfate and aminoethylsulfonic acid are preferably used. and salts thereof; more preferably chondroitin sulfate and salts thereof; more preferably chondroitin sulfate and salts thereof; An example of the component (B) is sodium androitin sulfate. This is also advantageous from the viewpoint of further enhancing the inhibitory effect of corneal epithelial cells on adhesion to soluble SHCL. be.

[0047] In addition, from the viewpoint of further enhancing the inhibitory effect of pollen protein accumulation on ionic SHCL, As the component (B), preferably, chondroitin sulfate, aspartic acid, and the like are used. More preferably, chondroitin sulfate and its salts; more preferably, chondroitin sulfate and its salts. An example is sodium salt.

[0048] In the ophthalmic composition for SHCL of the present invention, the blending ratio of the component (B) is determined by the type of the component (B). The ratio is appropriately set depending on the type of the (A) component to be used in combination. For example, The total amount of the component (B) is 0.001 to 5.0 w / v%, preferably 0. More specifically, the concentration of the ophthalmic composition for SHCL is preferably 1 to 1.5 w / v % based on the total amount of the ophthalmic composition for SHCL. The blending ratio of each of the (B) components is exemplified by the following ranges. (B) When the component is chondroitin sulfate and / or its salt: These are the total amounts, usually 0 .001 to 5.0 w / v%, preferably 0.01 to 2.0 w / v%, more preferably 0. 1~1.0w / v%; When component (B) is aminoethylsulfonic acid and / or its salt: These are the total amounts. Usually, it is 0.001 to 5.0 w / v%, preferably 0.01 to 2.0 w / v%, and more preferably 0.1~1.5w / v%; When the component (B) is aspartic acid and / or its salts: These are the total amounts, usually 0.0 0.01 to 5.0 w / v%, preferably 0.01 to 2.0 w / v%, more preferably 0.1 to 1.5w / v%.

[0049] The blending ratio of the above component (B) is determined based on the adhesion inhibitory effect of corneal epithelial cells against non-ionic SHCL. It has been further improved in its effectiveness in suppressing the accumulation of pollen proteins in ionic SHCL. Furthermore, the blending ratio of the above component (B) is preferably It is also preferable from the viewpoint of further enhancing the effect of inhibiting adhesion of corneal epithelial cells to the surface of the corneal epithelium.

[0050] In the ophthalmic composition for SHCL of the present invention, the ratio of component (B) to component (A) is Regarding the effect of inhibiting lipid adsorption to non-ionic SHCL, although there is no particular limitation, or to further enhance the inhibitory effect on the accumulation of pollen proteins in ionic SHCL. From this viewpoint, the total amount of the (B) component is 0.5 parts by weight per 100 parts by weight of the (A) component. The range is, for example, from 50 to 50,000 parts by weight, preferably from 50 to 10,000 parts by weight. Specifically, the ratio of each of the (B) components per 100 parts by weight of the total amount of the (A) component is as follows: The range is illustrated: (B) When the component is chondroitin sulfate and / or its salt: These are the total amounts, usually 0 0.5 to 50,000 parts by weight, preferably 5 to 10,000 parts by weight, more preferably 50 to 50 00 parts by weight; When component (B) is aminoethylsulfonic acid and / or its salt: These are the total amounts. Usually, it is 0.5 to 50,000 parts by weight, preferably 5 to 20,000 parts by weight, and more preferably 50 to 10000 parts by weight; When the component (B) is aspartic acid and / or its salts: These are the total amounts, usually 0.5 ~50,000 parts by weight, preferably 5 to 20,000 parts by weight, more preferably 50 to 1,000 0 parts by weight.

[0051] The ophthalmic composition for SHC of the present invention may further contain a buffering agent. Buffers that can be incorporated into the ophthalmic composition for L include those that are medically, pharmacologically (pharmaceutical) or physiologically There are no particular limitations on the buffering agent, so long as it is environmentally acceptable. Buffers, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, Tris buffer, ipsilateral buffer These include 1-aminocaproic acid, aspartic acid, and aspartic acid salts. The buffering agents may be used in combination. Preferred buffering agents are borate buffer, phosphate buffer, etc. , carbonate buffers, and citrate buffers, more preferred buffers are borate buffers, and A phosphate buffer is preferred, and a borate buffer is particularly preferred. The borate buffer is , boric acid, or borates such as alkali metal borates and alkaline earth metal borates. Phosphate buffers include phosphoric acid, alkali metal phosphates, alkaline earth phosphates, etc. Examples of the carbonate buffer include carbonate or an alkali metal carbonate salt. Examples of the citrate buffer include citric acid, , alkali metal citrate, alkaline earth metal citrate, etc. As the borate or phosphate buffer, borate or phosphate hydrates may be used. As a more specific example, boric acid or its salts (sodium borate, tetrahydrofuran, etc.) are used as boric acid buffers. potassium borate, potassium metaborate, ammonium borate, borax, etc.); phosphate buffer Phosphoric acid or its salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, phosphoric acid Potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium hydrogen phosphate, Calcium dihydrogen phosphate, etc.); Carbonic acid or its salts (sodium bicarbonate) as a carbonate buffer , sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate as citrate buffer, citric acid or its salts (sodium citrate, etc.) Sodium, potassium citrate, calcium citrate, sodium dihydrogen citrate, citric acid disodium, etc.); acetic acid buffer, acetic acid or its salts (ammonium acetate, potassium acetate, etc.) acetate, calcium acetate, sodium acetate, etc.; Tris buffers such as Tris(hydroxymethyl ethyl)aminomethane or its salts (hydrochloride, acetate, sulfonate, etc.); aspartic acid or The salt is (Sodium aspartate, magnesium aspartate, potassium aspartate, etc. Among these buffers, boric acid buffer is more effective in achieving the effects of the present invention. It is therefore suitable for use in the ophthalmic composition for SHCL of the present invention. These buffers may be used alone or in any combination of two or more. This is also fine.

[0052] When a buffering agent is blended in the ophthalmic composition for SHCL of the present invention, the blending ratio of the buffering agent is as follows: Depending on the type of buffer used, the types and amounts of other ingredients, the formulation form of the ophthalmic composition, etc. The amount of the ophthalmic composition for SHCL varies depending on the composition and cannot be uniformly defined. The total amount of the buffer is 0.01 to 10 w / v%, preferably 0.1 to 5 w / v%, more preferably 0.01 to 10 w / v%. A preferable ratio is, for example, 0.5 to 2 w / v %.

[0053] The ophthalmic composition for SHCL of the present invention may further contain an isotonicity agent. The tonicity agent that can be incorporated in the ophthalmic composition for CL is a medicinal, pharmacological (pharmaceutical) or biocompatible agent. There are no particular limitations on the isotonicity agent as long as it is physiologically acceptable. For example, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, Sodium hydrogen sulfate, sodium sulfite, potassium chloride, calcium chloride, sodium chloride Magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate sodium, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol, etc. Among these isotonicity agents, the one that can more reliably exert the effects of the present invention is From this viewpoint, sodium chloride, potassium chloride, calcium chloride, magnesium chloride are preferable. These tonicity agents include glycerin, propylene glycol, and propylene glycol. They may be used alone or in any combination of two or more.

[0054] When an isotonicity agent is incorporated into the ophthalmic composition for SHCL of the present invention, the mixing ratio of the isotonicity agent is The amount of isotonicity varies depending on the type of isotonicity agent used, and cannot be uniformly specified. For example, the total amount of the isotonic agent is 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%. More preferably, the ratio is 0.1 to 3 w / v %, for example.

[0055] The ophthalmic composition for SHCL of the present invention may further contain a surfactant. Surfactants that can be incorporated into the ophthalmic composition for HCL include those that are medically, pharmacologically (pharmaceutical) or There are no particular limitations on the surfactants, so long as they are physiologically acceptable. The surfactant may be any of a surfactant, an anionic surfactant, and a cationic surfactant.

[0056] Specific examples of nonionic surfactants that can be incorporated in the ophthalmic composition for SHCL of the present invention include: POE(20) sorbitan monolaurate (polysorbate 20), monopalmitin Polysorbate 40, POE(20) monostearate, POE(20) sorbitan Sorbitan (Polysorbate 60), POE(20) Tristearate Sorbitan (Poly sorbate 65), POE(20) sorbitan monooleate (polysorbate 80), etc. POE sorbitan fatty acid esters; Poloxamer 407, Poloxamer 235, Poloxamer Poloxamer 188, Poloxamer 403, Poloxamer 237, Poloxamer 124, etc. OE·POP block copolymers; POE(60) hydrogenated castor oil (polyoxyethylene POE hydrogenated castor oils such as hydrogenated castor oil 60); POE (9) lauryl ether, etc. E Alkyl ethers; POE(20)POP(4) cetyl ether and other POE-POPs Alkyl ethers: POE alkyl phenyl ether such as POE(10) nonylphenyl ether In the above-listed compounds, POE stands for polyoxyethylene. POP is polyoxypropylene, and the numbers in parentheses indicate the number of moles added. Specific examples of amphoteric surfactants that can be incorporated into the ophthalmic composition for SHCL of the present invention include: Examples of the ophthalmic composition for SHCL of the present invention include alkyldiaminoethylglycine. Specific examples of cationic surfactants that can be blended include benzalkonium chloride, Benzethonium and the like are exemplified. In addition, an anion that can be added to the ophthalmic composition for SHCL of the present invention is Specific examples of the ionic surfactant include alkylbenzene sulfonate and alkyl sulfate. Salts, polyoxyethylene alkyl sulfates, aliphatic α-sulfomethyl esters, α-olefins Examples include sulfonic acids.

[0057] In the ophthalmic composition for SHCL of the present invention, the above-mentioned surfactants may be used alone. It is also possible to use two or more of them in combination.

[0058] Among the above surfactants, nonionic surfactants are preferred; POE is more preferred. Sorbitan fatty acid esters, POE hydrogenated castor oils, or POE-POP block copolymers Rimers are used.

[0059] When a surfactant is added to the ophthalmic composition for SHCL of the present invention, the mixing ratio of the surfactant Regarding the type of the surfactant, the type and amount of other blended ingredients, the ophthalmic composition for SHCL The mixing ratio of the surfactant can be appropriately set depending on the formulation, etc. The total amount of the surfactant is preferably 0.001 to 1.0 w / v% based on the total amount of the composition. A preferred range is 0.005 to 0.7 w / v%, and a more preferred range is 0.01 to 0.5 w / v%. do.

[0060] The pH of the ophthalmic composition for SHCL of the present invention is determined from the viewpoints of medicine, pharmacology (pharmaceutical) or There are no particular limitations as long as it is within a physiologically acceptable range. The pH of the ophthalmic composition is, for example, 2.5 to 9.5, preferably 3.0 to 9.0, and more preferably A range of 3.5 to 8.5 is also preferred.

[0061] In addition, the osmotic pressure of the ophthalmic composition for SHCL of the present invention is within the range acceptable to the living body. As an example of the osmotic pressure ratio of the ophthalmic composition for SHCL of the present invention, Preferably, it is 0.5 to 5.0, more preferably 0.6 to 3.0, and particularly preferably 0.7 to 2. The range where the osmotic pressure is 0 is the range where the osmotic pressure is 0. The osmotic pressure can be adjusted by using inorganic salts, polyhydric alcohols, sugar alcohols, and sugars. The osmolality ratio can be determined by methods known in the art using, for example, 15th Amendment Based on the Japanese Pharmacopoeia, the osmotic pressure of 286 mOsm (0.9 w / v% sodium chloride solution) The osmotic pressure is the ratio of the osmotic pressure of the sample to that of the sample. The osmotic pressure is measured by the osmotic pressure measurement method (freezing point depression method) described in the Japanese Pharmacopoeia. Use this as a reference for the measurement. The solution is sodium chloride (Japanese Pharmacopoeia standard reagent) dried at 500-650℃ for 40-50 minutes. After drying, leave it to cool in a desiccator (silica gel), and then weigh 0.900 g of it accurately. Dissolve in purified water to make exactly 100 mL, or use a commercially available standard solution for measuring osmolality ratio (0.9 w / v% sodium chloride aqueous solution) is used.

[0062] The ophthalmic composition for SHCL of the present invention may contain various other components in addition to the above components, as long as the effects of the present invention are not impaired. The pharmaceutical composition may contain a combination of various pharmacologically active ingredients and physiologically active ingredients in appropriate amounts. For example, the OTC Drug Manufacturing (Import) Approval Standards 2000 Edition (Pharmaceutical Affairs and Research Examples of active ingredients in ophthalmic drugs listed in the ophthalmic drug safety standards (supervised by the Japan Society of Ophthalmic Drugs) are listed below. The ingredients used in this study include the following: Antihistamines: e.g. , iproheptine, diphenhydramine hydrochloride, chlorpheniramine maleate, fumaric acid Ketotifen, pemirolast potassium, etc. Decongestants: e.g., tetrahydrozoline hydrochloride , naphazoline hydrochloride, naphazoline sulfate, epinephrine hydrochloride, ephedrine hydrochloride, methionine hydrochloride Chilephedrine, etc. Bactericides: e.g., cetylpyridinium, benzalkonium chloride, salts Benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, polyhexidine hydrochloride Samethylene biguanide, etc. Vitamins: e.g., cyanocobalamin, retinol acetate, paclitaxel, etc. Retinol lutate, panthenol, calcium pantothenate, etc. Anti-inflammatory agents: e.g. Dipotassium ricyrrhizinate, Pranoprofen, Allantoin, Azulen, Azulensul Sodium caprylate, guaiazulene, ε-aminocaproic acid, berberine chloride, berberine sulfate Verin, lysozyme chloride, licorice, etc. Astringents: For example, zinc oxide, zinc lactate, zinc sulfate, etc. Others: For example, sodium cromoglycate, sulfamethoxazole, sulfamethoxazole zole sodium and the like.

[0063] In addition, the ophthalmic composition for SHCL of the present invention may contain any of the following substances within the scope of the present invention, so long as the effects of the present invention are not impaired. Depending on the purpose and form of the product, various additives are appropriately selected according to the usual method, and one or more types are mixed together. The additives may be, for example, those listed in the Pharmaceutical Additives Encyclopedia 20. Examples of additives include those listed in 07 (edited by the Japan Pharmaceutical Additives Association). The following additives are included: Carrier: For example, an aqueous carrier such as water or aqueous ethanol. Thickeners: e.g., carboxyvinyl polymers, hydroxyethyl cellulose, hydro xypropyl methylcellulose, methylcellulose, alginic acid, polyvinyl alcohol (completely or partially saponified), polyvinylpyrrolidone, macrogol, etc. Sugars: for example, cyclodextrin. Sugar alcohols: For example, xylitol, sorbitol, mannitol, etc. may be any of the d-, l- or dl-forms. Preservatives, bactericides or antibacterial agents: e.g., alkyldiaminoethylglycine hydrochloride, benzoin Sodium chloride, ethanol, benzalkonium chloride, benzethonium chloride, chlorinated gluconate Lorhexidine, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate Thorium, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, parahydroxybenzoic acid Propyl, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, butyl paraoxybenzoate benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, etc.) , Glokill (product name manufactured by Rhodia), etc. pH adjusters: e.g., hydrochloric acid, boric acid, epsilon-aminocaproic acid, citric acid, vinegar Acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, carbonic acid Sodium bicarbonate, sodium carbonate, borax, 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, acetic acid Ammonium etc. Stabilizers: e.g. dibutylhydroxytoluene, trometamol, sodium formate Mulaldehyde sulfoxylate (Rongalite), tocopherol, sodium pyrosulfite , Monoethanolamine, Aluminum Monostearate, Glyceryl Monostearate Ng et al. Chelating agents: e.g., ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid Acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), N-(2-hydroxyethyl) ethylenediamine ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), and the like. Fragrances or fresheners: For example, menthol, anethole, eugenol, camphor, geranium Laniol, cineol, borneol, limonene, ryuno, etc. These are d- and l-isomers. Either the dl form or the dl form may be used, and essential oils (peppermint oil, cool mint oil, spearmint oil, etc.) , peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil, etc. ) may also be used.

[0064] The ophthalmic composition for SHCL of the present invention comprises desired amounts of the above-mentioned components (A) and (B), and optionally Other ingredients are added as necessary to obtain the desired concentration.

[0065] The ophthalmic composition for SHCL of the present invention may be in the form of a drug as long as it can be used in the field of ophthalmology. Although not particularly limited, examples thereof include liquid and ointment. Among liquids, an aqueous liquid is preferred. When in liquid form, the aqueous carrier is water that is medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable. As such water, specifically, distilled water, tap water, purified water, sterilized water, etc. may be used. Examples include purified water, water for injection, and distilled water for injection. These definitions are based on the 15th revised edition of the Japanese Pharmacopoeia. Here, the aqueous liquid means a liquid form containing water, and is usually based on SHCL. The ophthalmic composition for use contains water in an amount of 1% by weight or more, preferably 5% by weight or more, more preferably 20% by weight or more. % or more, and more preferably 50% by weight or more.

[0066] The ophthalmic composition for SHCL of the present invention is used in the ophthalmic field and is in contact with SHCL. There are no restrictions on the formulation, so long as it is used for the purpose described above. HCL eye drops (eye drops that can be used while wearing SHCL), SHCL eyewash (SH Eyewash that can be used while wearing CL), SHCL wearing solution, SHCL care solution (SHC Disinfectant, SHCL preservation solution, SHCL cleaning solution, and SHCL cleaning and preservation solution, etc. This can be done.

[0067] Among these, SHCL eye drops can be easily used while wearing SHCL, so Effectively prevents the adhesion of lipid stains and the accumulation of pollen proteins while wearing CL. Therefore, it is said that it is possible to prevent discomfort while wearing SHCL and make it comfortable to wear SHCL. In addition, the eye drops or the SHCL wetting solution, particularly the eye drops The agent may be administered during or immediately prior to contact of the SHCL with the ocular surface (e.g., It is used within 10 minutes before the act of wearing the product, which is considered to be a cause of injury, and has a high degree of sensitivity to non-ionic SHCL. This is a formulation that is highly required to inhibit adhesion of membranous epithelial cells. The effect of the present invention can be more effectively achieved because the formulation is used frequently. Considering all these points, the following is a preferred example of the ophthalmic composition for SHCL of the present invention: , and eye drops for SHCL.

[0068] In addition, the method for using the ophthalmic composition for SHCL of the present invention includes the steps of: There are no particular limitations as long as the method is a known method that includes a step of contacting the SHCL. For example, in the case of SHCL eye drops, an appropriate amount of the eye drops is instilled into the eye before or during the wearing of the SHCL. In the case of SHCL eyewash, the eyewash should be used before or during the wearing of the SHCL. In addition, the ophthalmic composition for SHCL of the present invention can be used as an eye drop for SHCL. If the product is an eyewash or SHCL eyewash, it should be used not only while wearing the SHCL but also when not wearing it. It can be used for eye drops and eye washing even when the patient is not wearing eye drops. The solution is used by contacting an appropriate amount of the SHCL with the HCL when the HCL is attached. In the case of HCL care liquid, immerse SHCL in an appropriate amount of the care liquid, or It is used by contacting SHCL with a cleaning liquid and scrubbing it.

[0069] In the ophthalmic composition for SHCL of the present invention, the type of SHCL to be applied is not particularly limited. Any currently or future commercially available, whether ionic or non-ionic, All commercially available SHCLs can be used. According to the ophthalmic composition for SHCL of the present invention, In the case of non-ionic SHCL, the lipid adsorption to non-ionic SHCL is important. It was also found that the adhesion of corneal epithelial cells to non-ionic SHCL was suppressed. In addition, when ionic SHCL is used as the target of application, the pollen concentration of ionic SHCL is considered to be high. It is possible to suppress protein accumulation. In accordance with the standards of the Food and Drug Administration, the content of ionic components in the contact lens material is 1 mol % or more, and non-ionic means that the contact lens material is made according to the US FDA standards. This means that the content of ionic components in the material is less than 1 mol%.

[0070] In addition, in the ophthalmic composition for SHCL of the present invention, the water content of the SHCL to be applied is There is no particular limitation on the amount of the saturation. For example, it is 90% or less, preferably 60% or less, and more preferably 5 0% or less. Note that SHCL contains hydrogel material, so In particular, non-ionic SHCL with a water content of 35% or less In particular, the adhesiveness to corneal epithelial cells tends to be strong. Therefore, the adhesion of non-ionic SHCL to corneal epithelial cells was not observed in the corneal epithelium. In view of the effects of the present invention, the adhesion of membrane epithelial cells can be effectively suppressed. The ophthalmic composition for SHCL of the present invention is preferably applied to non-insulin-containing ophthalmic lenses having a water content of 35% or less. Examples of such SHCLs include:

[0071] The moisture content of SHCL refers to the proportion of water in SHCL, and is calculated using the following formula: It is calculated by:

[0072] Moisture content (%) = (weight of absorbed water / weight of SHCL in hydrated state) x 100 Moisture content required The rate can be measured by gravimetric methods as described in ISO 18369-4:2006. .

[0073] In addition, compared to non-silicone hydrogel contact lenses, which are generally made of soft materials, The hard SHCL can cause lens deformation and reduced wettability due to the adhesion of foreign matter, resulting in a poor wearing experience. The ophthalmic composition for SHCL of the present invention is easily irritated and tends to cause eye mucosa damage. According to the study, the hard material of SHCL is likely to cause discomfort and eye mucosa damage. It can effectively suppress the adsorption and accumulation of lipids and pollen proteins, thereby preventing changes in the lens. It is also possible to prevent the shape and quality from changing, and effectively prevent deterioration of the feeling of use and damage to the eye mucosa. In view of the effects of the present invention, the ophthalmic composition for SHCL of the present invention is preferably applied to ophthalmic lenses having a hardness of 100 mm or less. The hardness of the SHCL to be applied is preferably below 100%. The hardness measured by the texture analyzer method described above is 3g or more. It is preferably 4 g or more, more preferably 6 g or more, and even more preferably 8 g or more. The upper limit of the hardness of the SHCL to be applied is not particularly limited, but is preferably 1. It is preferably 5 g or less, and more preferably 12 g or less.

[0074] The hardness of contact lenses is measured using a texture analyzer (product name: TA.XT.plus TEXTURE The measurement was carried out using an ANALYSER (manufactured by Stable Micro Systems Limited) as follows: It can be determined.

[0075] First, remove the contact lenses to be measured from the package and wipe off any excess moisture. It was removed, rinsed with saline (0.9% sodium chloride solution), and then filled with saline. The sample is placed on the bottom of a plastic petri dish with the convex side facing up. The contact lens is adjusted so that it is directly under the contact lens, and the measurement is carried out under the following measurement conditions.

[0076] [Measurement conditions] Instrument settings: Test mode Compression measurement Probe type: φ10mm cylinder probe Target Mode Distance Distance 2.5mm Trigger Type: Auto Trigger Force 0.1g Test Speed ​​1.0mm / sec The lens is crushed for 2.5 mm (2.5 seconds) after the probe starts to press down on the apex of the lens. The stress during bending is measured and the maximum value is recorded as the hardness.

[0077] The ophthalmic composition for SHCL of the present invention has inherent physiological activity based on the above components (A) and (B). For example, based on components (A) and (B), It is said that it promotes the metabolism of eye cells and relieves eye fatigue, which is effective in improving eye function. It can be used to improve fatigue or tired eyes.

[0078] In addition, conventional hard contact lenses made of polymethyl methacrylate (PMMA) The lens may adhere to the cornea, causing corneal epithelial damage (3 o'clock to 9 o'clock staining). It is known that wearing SCLs can easily cause dry eye symptoms. Person who does In some patients (e.g., dry eye patients), the cornea is easily damaged by the lens, resulting in corneal staining. On the other hand, non-ionic SHCL is known to be prone to keratitis and corneal epithelial cells. The unique properties of silicone hydrogel contact lenses, as well as their remarkable adhesive properties, Generally, the material is harder than that of ordinary non-silicone SCLs, so it is unlikely to cause physical damage to the corneal epithelium. Considering these characteristics of non-ionic SHCL, It is clear that the use of contact lenses can easily cause the above-mentioned corneal epithelium disorders. In contrast, the ophthalmic composition for SHCL of the present invention is capable of binding to non-ionic SHCL of corneal epithelial cells. It can effectively suppress adhesion of dentin, and therefore, prevent corneal edema caused by wearing non-ionic SHCL. Therefore, the ophthalmic composition for SHCL of the present invention can prevent the membrane epithelium damage. It can be used as a preventive agent for corneal epithelial damage caused by wearing a corneal SHCL. In particular, it is suitable for use by those who suffer from dry eyes (e.g., dry eye patients). do.

[0079] In addition, corneal epithelial cells also have a barrier function against allergens, etc. The corneal epithelium damage caused by the use of non-ionic SHCL is thought to be due to the impairment of its barrier function. This may reduce the amount of oxygen in the blood and make it easier for the eye to develop allergic symptoms. According to the ophthalmic composition for SHCL, the adhesion of corneal epithelial cells to non-ionic SHCL is suppressed. This maintains the corneal epithelial cells in a normal state and maintains the barrier function of the corneal epithelial cells. Therefore, the ophthalmic composition for SHCL of the present invention is capable of maintaining the non-ionic SHCL. CL users can increase their resistance to various eye diseases, including allergies, and prevent them. The present invention is preferably used as a preventive agent for eye diseases (for example, a preventive agent for allergic symptoms) for preventing eye diseases.

[0080] In addition, the ophthalmic composition for SHCL of the present invention is characterized in that lipid adsorption to nonionic SHCL is a factor. This effectively prevents corneal staining and other corneal epithelial disorders caused by the From this viewpoint, the present invention can be effectively used as a preventive agent for corneal epithelial disorders.

[0081] Furthermore, the ophthalmic composition for SHCL of the present invention is capable of removing pollen proteins from ionic SHCL. This promotes the removal of pollen and prevents reattachment, which effectively prevents the accumulation of pollen proteins on ionic SHCL. Therefore, the pollen proteins adsorbed on the contact lenses can be effectively suppressed. This prevents continued contact with pollen and is also effective in preventing or worsening pollen-related allergies. Therefore, it is suitable for use by ionic SHCL users who suffer from hay fever or are at risk of suffering from hay fever.

[0082] 2. Methods for suppressing lipid adsorption to non-ionic SHCL and lipid adsorption to non-ionic SHCL Method for imparting adhesion suppression effect As described above, by using the above components (A) and (B) in combination, the nonionic SH It is possible to suppress the adsorption of lipids to CL.

[0083] Therefore, from another aspect, the present invention provides: (A) flavin adenine dinucleotide, pyrimidine; (B) at least one selected from the group consisting of toxins and salts thereof; and (C) chondroitin. Selected from the group consisting of tin sulfate, aminoethylsulfonic acid, aspartic acid, and salts thereof. and contacting the non-ionic SHCL with an ophthalmic composition for SHCL containing at least one selected from the group consisting of ethylhexyl ether, ... The present invention provides a method for suppressing the adsorption of lipids to nonionic SHCL, the method comprising contacting the lipids with nonionic SHCL. Furthermore, the ophthalmic composition for SHCL contains (A) flavin adenine dinucleotide, pyridoxine. (B) at least one selected from the group consisting of chondroitin and salts thereof; selected from the group consisting of aminosulfonic acid, aminoethylsulfonic acid, aspartic acid, and salts thereof The ophthalmic composition for SHCL is characterized by comprising at least one nonionic surfactant. The present invention provides a method for imparting an inhibitory effect on lipid adsorption to hydrophobic SHCL.

[0084] In these methods, the types and mixing ratios of components (A) and (B), and other components to be mixed are The type and mixing ratio of the ophthalmic composition for SHCL, the formulation form of the ophthalmic composition for SHCL, and the non-ionic SHC to be applied The type of L, etc. are the same as those in "1. Ophthalmic composition for SHCL" above.

[0085] 3. Method for inhibiting accumulation of pollen proteins in ionic SHCL and ionic SHC A method for imparting an effect of suppressing accumulation of pollen proteins to L. In addition, as described above, by using the above components (A) and (B) in combination, ionic Even if the SHCL-wearing eye is exposed to pollen, the ionic SHCL promotes the removal of pollen proteins from the SHCL. This prevents the accumulation of pollen proteins on ionic SHCL by promoting the adhesion of pollen to the SHCL and preventing redeposition. This makes it possible.

[0086] Therefore, from another aspect, the present invention provides: (A) flavin adenine dinucleotide, pyrimidine; (B) at least one selected from the group consisting of toxins and salts thereof; and (C) chondroitin. Selected from the group consisting of tin sulfate, aminoethylsulfonic acid, aspartic acid, and salts thereof. and contacting an ophthalmic composition for SHCL containing at least one selected from the group consisting of ionic SHCL and A method for inhibiting accumulation of pollen proteins in ionic SHCL, comprising: Further, the ophthalmic composition for SHCL comprises: (A) flavin adenine dinucleotide; (B) at least one selected from the group consisting of pyridoxine and salts thereof; The group consisting of leucine sulfate, aminoethylsulfonic acid, aspartic acid, and salts thereof The present invention relates to a method for adding pollen to an ionic SHCL, comprising the steps of: The present invention provides a method for imparting the effect of inhibiting protein accumulation to the ophthalmic composition.

[0087] In these methods, the types and mixing ratios of components (A) and (B), and other components to be mixed are The type and mixing ratio of , the formulation form of the ophthalmic composition for SHCL, and the ionic SHCL to which it is applied The types etc. are the same as those in "1. Ophthalmic composition for SHCL" above.

[0088] 4. Method for inhibiting adhesion of corneal epithelial cells to non-ionic SHCL and non-ionic SHC Method for imparting inhibitory effect of corneal epithelial cells to L. As described above, by using the above components (A) and (B) in combination, the nonionic SH It is possible to inhibit the adhesion of corneal epithelial cells to CL.

[0089] Therefore, from another aspect, the present invention provides: (A) flavin adenine dinucleotide, pyrimidine; (B) at least one selected from the group consisting of toxins and salts thereof; and (C) chondroitin. Selected from the group consisting of tin sulfate, aminoethylsulfonic acid, aspartic acid, and salts thereof. and contacting the non-ionic SHCL with an ophthalmic composition for SHCL containing at least one selected from the group consisting of ethylhexyl ether, ... Inhibits adhesion of corneal epithelial cells to non-ionic SHCL. Further, the present invention provides an ophthalmic composition for SHCL, comprising (A) flavin adenine dinucleotide. (B) at least one selected from the group consisting of tido, pyridoxine, and salts thereof; Consists of chondroitin sulfate, aminoethylsulfonic acid, aspartic acid, and their salts. An ophthalmic composition for SHCL, comprising at least one selected from the group consisting of To provide a method for imparting an inhibitory effect on adhesion of corneal epithelial cells to non-ionic SHCL to a substance. .

[0090] In these methods, the types and mixing ratios of components (A) and (B), and other components to be mixed are The type and mixing ratio of the ophthalmic composition for SHCL, the formulation form of the ophthalmic composition for SHCL, and the non-ionic SHC to be applied The type of L, etc. are the same as those in "1. Ophthalmic composition for SHCL" above. EXAMPLES

[0091] The present invention will be described in detail below with reference to examples. The present invention is not limited to the above.

[0092] Reference Test Example 1: Evaluation of lipid adsorption properties of various SCLs The following experiments were carried out using various soft contact lenses shown in Table 1. The lipid adsorption of soft contact lenses was evaluated. Both are commercially available products.

[0093] [Table 1]

[0094] First, fluorescently labeled lipid (N-(fluorescein-5-thiocarbamoyl)-1,2-dihexadecanoyl-s n-glycero-3-phosphoethanolamine, triethylammonium salt; manufactured by Invitrogen) 1 mg / A mixture of chloroform and methanol in a volume ratio of 1:4 containing 5 mL of Physiological saline (0.9 w / v% sodium chloride) was added to 100 μL to make the total volume 20 mL. The fluorescent lipid solution was prepared by soaking the soft contact lenses in saline for at least one night. The samples were pretreated by immersing them in 24-well microplates. Each soft contact lens was immersed in 1 mL of the fluorescent lipid solution at 34°C for 24 h. In addition, as a blank group, each soft contact lens was placed in 1 mL of physiological saline. Each lens was immersed in the solution and shaken in the same manner as the sample group. After 24 hours, Each soft contact lens was transferred to a plate containing 1 mL of fresh saline and the fluorescent plate was The fluorescence intensity of each well was measured using a readout reader (Thermo Fisher Scientific Inc.). The fluorescence intensity of the samples was measured (excitation wavelength: 485 nm, emission wavelength: 538 nm). The value obtained by subtracting the fluorescence intensity of each rank group was calculated as an index of the amount of adsorbed lipid.

[0095] The results are shown in Figure 1. As is clear from Figure 1, the non-ionic SHCL (lenses A and B) The amount of lipid adsorption was measured for ionic SHCL (Lens C) and conventional hydrogel lenses (Lens This indicates that the problem of lipid fouling is serious, as it is significantly higher than that of the samples D to F.

[0096] Test Example 1: Evaluation of lipid adsorption inhibition by non-ionic SHCL (1) Using non-ionic SHCL (Lens A), which was found to have significant lipid adsorption in the above Reference Test Example 1, Using each test solution shown in Table 2 below, the effect of non-ionic SHCL on lipid adsorption was examined. We conducted an investigation into this issue.

[0097] [Table 2]

[0098] First, fluorescently labeled lipid (N-(fluorescein-5-thiocarbamoyl)-1,2-dihexadecanoyl-s 1mg / n-glycero-3-phosphoethanolamine, triethylammonium salt (manufactured by Invitrogen) 500μL of a mixture of chloroform and methanol in a volume ratio of 1:4 was added to the flask. Physiological saline (0.9 w / v% sodium chloride) was added to make a total volume of 20 mL, and the solution was then placed in a fluorescent liposome. Lens A was pretreated by soaking in saline overnight. Then, 500 μL of each test solution (Example 1) was added to each well of a 24-well microplate. 1-3 and Comparative Example 1-5) and 1500 μL of fluorescent lipid solution were placed in it, and the test pretreatment was performed. After the above, the lenses A were immersed one by one in the solution and shaken for 24 hours at 34°C (sample group). In addition, 500 μL of each test solution (Examples 1-3 and Comparative Examples 1-5) and A well was prepared by adding 1500 μL of physiological saline to the lens, and the lens was placed in the well after the pretreatment. Each piece of sieve A was immersed in the same manner and shaken (blank group). After 24 hours, After the treatment, each lens A was transferred to a plate containing 1 mL of fresh saline, and the fluorescent plate The fluorescence intensity of each well was measured using a FluoreReader (Thermo Fisher Scientific Inc.). (Excitation wavelength: 485 nm, Fluorescence wavelength: 538 nm) The value obtained by subtracting the fluorescence intensity of the rank group was used as an index of the amount of adsorbed lipid. The relative value (%) of the amount of adsorbed lipid in each test solution was calculated when the amount of adsorbed lipid in 1) was taken as 100%. Ta.

[0099] The results are shown in FIG. 2. As shown in FIG. When sodium was used alone (Comparative Example 2), the lipid adsorption inhibitory effect was greater than that of the control. On the other hand, completely unexpectedly, this lipid adsorption suppression effect was almost completely suppressed by Flavin adenine dinucleotide sodium salt not shown, and sodium chondroitin sulfate , aminoethylsulfonic acid, or potassium aspartate ( In Example 1-3), it was found that lipid adsorption to non-ionic SHCL can be synergistically suppressed. was shown.

[0100] Test Example 2: Evaluation of lipid adsorption inhibition by non-ionic SHCL (2) Using non-ionic SHCL (Lens A), which was found to have significant lipid adsorption in the above Reference Test Example 1, Using each test solution shown in Table 3 below, the effect of non-ionic SHCL on lipid adsorption was examined. We conducted an investigation into this issue.

[0101] [Table 3]

[0102] First, fluorescently labeled lipid (N-(fluorescein-5-thiocarbamoyl)-1,2-dihexadecanoyl-s 1mg / n-glycero-3-phosphoethanolamine, triethylammonium salt (manufactured by Invitrogen) 500μL of a mixture of chloroform and methanol in a volume ratio of 1:4 was added to the flask. Physiological saline (0.9 w / v% sodium chloride) was added to make a total volume of 20 mL, and the solution was then placed in a fluorescent liposome. Lens A was pretreated by soaking in saline overnight. Then, 500 μL of each test solution (Example 1) was added to each well of a 24-well microplate. 4-6, and Comparative Examples 1 and 3-6) and 1500 μL of fluorescent lipid solution was placed in it. After the pre-treatment, the lenses A were immersed one by one in the solution and shaken at 34°C for 24 hours. In addition, 500 μL of each test solution (Examples 4-6 and Comparative Examples) was used as a blank group. Comparative Examples 1 and 3-6) and 1500 μL of physiological saline were placed in a well. After the pre-treatment, the lenses A were immersed one by one and shaken in the same manner (blank group). After 24 hours, each lens A that had been shaken was placed in a plate containing 1 mL of fresh saline. The cells were transferred to a fluorescent plate reader (Thermo Fisher Scientific Inc.) and each cell was analyzed. The fluorescence intensity of each sample was measured (excitation wavelength: 485 nm, fluorescence wavelength: 538 nm). The fluorescence intensity of the blank group was subtracted from the fluorescence intensity of the fluorophore group to obtain an index of the amount of adsorbed lipid. The value of each test solution was calculated assuming the control (Comparative Example 1) to be 100%.

[0103] The results are shown in Figure 3. As shown in Figure 3, when pyridoxine hydrochloride was used alone, In (Comparative Example 6), it was found that there was no lipid adsorption suppression effect at all compared to the control. On the other hand, completely unexpectedly, pyridoxine hydrochloride showed no lipid adsorption inhibitory effect. and sodium chondroitin sulfate, aminoethylsulfonic acid, or potassium aspartate. When used in combination with ammonium (Examples 4-6), the lipid permeability to nonionic SHCL was It was shown that the adsorption of sorbent was synergistically suppressed by both the sorbent and the glycerol.

[0104] Reference Test Example 2: Evaluation of corneal epithelial cell adhesion to various SCLs The following experiment was carried out using the five types of soft contact lenses shown in Table 4. The adhesion of corneal epithelial cells to the surface of the tact lens was evaluated. All of the tact lenses are commercially available.

[0105] [Table 4]

[0106] Specifically, the evaluation was performed by the following method. Each soft contact lens was placed in a 24-well microplate containing 900 μL of the above solution. Each well was immersed in one of the plates with the convex side facing up. The cells of the prepared rabbit corneal epithelial cell line SIRC (ATCC number: CCL-60) Cell suspension (1 x 10 5100μL of each medium (cells / mL) was seeded and incubated at 37℃ under 5% CO2. After culturing for 48 hours under these conditions, the number of viable cells attached to the soft contact lenses was counted. As a control, no lenses were immersed and the cells were placed on the bottom of the microplate. The cells were cultured and the number of viable cells in the wells was counted (control group). The Cell Counting Kit (Dojindo Laboratories, Ltd.) was used for the control. The number of viable cells attached to the surface of each soft contact lens was calculated based on the total number of viable cells in the wells of the soft contact lens group. The percentage of viable cells adhering to the control group was calculated. I put it out.

[0107] The results are shown in Figure 4. As is clear from Figure 4, the non-ionic SHCL, Ren Lenses 1 and 2 are ionic SHCL lenses 3 and non-silicone hydrogel contact lenses. Compared to lenses 4 and 5, the lens showed significant corneal epithelial cell adhesion. In addition, when the adhesion of cells to soft contact lenses was observed under a microscope, Although almost no cell adhesion was observed on the surfaces of lenses 3, 4, and 5, the cells were It was confirmed that corneal epithelial cells were attached to the entire surface of the non-ionic It has been confirmed that SHCL has significantly higher adhesion of corneal epithelial cells than other types of lenses. It has become clear that the use of non-ionic SHCL can have adverse effects such as damage to the corneal surface. It became.

[0108] Test Example 3: Corneal epithelial cell adhesion inhibition test to non-ionic SHCL (1) Using the test solutions shown in Table 5, the adhesion inhibitory effect of corneal epithelial cells on non-ionic SHCL was was evaluated.

[0109] [Table 5]

[0110] Lens 2 (non-ionic SHCL) shown in Table 4 was subjected to each test solution (Example 1 and Comparative Example 2) shown in Table 5. Comparative Example 2-3) Each piece was immersed in 3 mL of the test solution and left to stand at 34°C for 24 hours. The lens 2 is lightly washed with saline, wiped off the moisture, and then placed in a growth medium (10% U). Place the plate in a 24-well plate containing 900 μL of fetal serum-containing DMEM medium, with the convex side facing up. Rabbit corneal epithelial cells conditioned with a growth medium were placed in each well. A cell suspension (1 × 10 5 ce ll / mL) were seeded in 100 μL portions and cultured at 37°C, 5% CO2 for 48 hours. The number of viable cells attached to the lens was counted (sample group). Instead of each test solution, lens 2 was immersed in the control test solution shown in Table 5. A cell suspension of rabbit corneal epithelial cell line was seeded and cultured under the same conditions as above to form lens 2. The number of attached viable cells was counted (control group). In addition, rabbit cornea was used as a blank. 1000μL of growth medium (DMEM medium containing 10% fetal bovine serum) without seeding epithelial cells A well was prepared by adding only the lens 2, which had not been immersed in the well, and the lens 2 was placed in the well at 37°C for 5 The plate was left to stand for 48 hours under 10% CO2 (blank group). Using a Counting Kit (Dojindo Laboratories), the cell adhesion inhibition rate (%) was calculated according to the following formula: was calculated.

[0111]

number

[0112] The results are shown in FIG. 5. As is clear from FIG. 5, When sodium chondroitin sulfate and sodium chondroitin sulfate were used in combination (Example 1) The inhibitory effect of non-ionic SHCL on corneal cell adhesion was significantly increased. It became clear.

[0113] Test Example 4: Corneal epithelial cell adhesion inhibition test to non-ionic SHCL (2) Using lens 2 (non-ionic SHCL) shown in Table 4, and using the test solution shown in Table 6 below, The inhibitory effect of non-ionic SHCL on corneal epithelial cell adhesion was evaluated.

[0114] [Table 6]

[0115] Using a growth medium (DMEM medium containing 10% fetal bovine serum), A test solution (Example 7-8) was prepared and filtered using a 0.2 μm membrane filter. After sterilization by filtration, each test solution was diluted 2-fold with the above growth medium and Put 900 μL of each solution into each well of the microplate, and then place lens 2 with the convex side facing up. In addition, the cells were immersed in a growth medium (DMEM medium containing 10% fetal bovine serum). The rabbit corneal epithelial cell line SIRC (ATCC number: CCL-60) was prepared by Cell suspension (1 × 10 5 100μL of each of 100 cells / mL was seeded and incubated at 37℃, 5% CO2 After culturing for 48 hours under these conditions, the number of viable cells attached to the lens 2 was counted (sample group). As a control, the test specimens were immersed in the control test liquids shown in Table 6 instead of the test liquids. Using the treated lens 2, a cell suspension of rabbit corneal epithelial cell line was seeded under the same conditions as above. The cells were cultured and the number of viable cells attached to the lens 2 was counted (control group). As a ranking, rabbit corneal epithelial cells were not seeded and the cells were grown in a growth medium (containing 10% fetal bovine serum). A well was prepared by adding only 1000 μL of MEM medium, and lens 2 was placed in the well at 37° C. The blank group was incubated for 48 hours under 5% CO2. Using the Cell Counting Kit (manufactured by Dojindo Laboratories, Ltd.), the same procedure as in Test Example 3 was carried out. The cell adhesion inhibition rate (%) was calculated using the same formula.

[0116] The results are shown in FIG. 6. As is clear from FIG. 6, flavin adenine dinucleotide Sodium is used in combination with aminoethylsulfonate or potassium aspartate. When the nonionic SHCL was used (Examples 7-8), the adhesion of corneal epithelial cells to nonionic SHCL was significantly increased. It was found that this could be effectively suppressed.

[0117] Test Example 5: Corneal epithelial cell adhesion inhibition test to non-ionic SHCL (3) Using the test solutions (Examples 9-10) shown in Table 7 below, the same method as in Test Example 4 was used. The inhibitory effect of non-ionic SHCL on the adhesion of corneal epithelial cells was evaluated.

[0118] [Table 7]

[0119] The results are shown in FIG. 7. As is clear from FIG. 7, pyridoxine hydrochloride and aminoethyl When used in combination with chondroitin sulfate or sodium chondroitin sulfate (Example 9) -10) was also able to effectively inhibit corneal epithelial cell adhesion to non-ionic SHCL. It became clear that...

[0120] Reference Test Example 3: Evaluation of pollen protein adsorption properties of soft contact lenses The four types of soft contact lenses shown in Table 8 were used in the test. The adsorption characteristics of pollen proteins to the cellulose were evaluated.

[0121] First, the lenses to be used in the test were immersed in 4 mL of physiological saline solution one by one and left at room temperature overnight. Stored (pretreatment of lenses).

[0122] Pollen protein antigen (Cedar Pollen Extract-Ja, manufactured by LSL Co., Ltd., properties :Lyophilized powder (Cedar Pollen crude extract Mountain ceder, Juniperus Asheii From the pollen of The extract was dissolved in physiological saline to prepare a 5 mg / 30 mL pollen protein solution. Add 1.0 mL of the pollen protein solution to each well of the well plate and immerse the excess of the pretreated lens. After wiping off the moisture, the sample was immersed and shaken at 34°C and 120 rpm for 18 hours. Remove the lens and quickly immerse it in 100 mL of saline (for about 1 second) to remove excess liquid. After rinsing, gently squeeze out the water using the edge of a beaker and place the pollen in each well of a 24-well plate. Immerse in 1 mL of protein separation solution (aqueous solution containing 1% sodium carbonate and 1% SDS). The mixture was shaken at 34°C and 120 rpm for 3 hours to remove the pollen proteins adsorbed on the lenses. The protein was separated in a protein separation solution.

[0123] Using the Micro BCA Assay Kit (Thermo Scientific, Pierce #23235), pollen The amount of pollen protein in the protein separation solution was quantified as an albumin equivalent value and applied to the lens. The amount of pollen protein adsorbed was then calculated.

[0124] [Table 8]

[0125] The hardness of each soft contact lens was measured using a texture analyzer ( Product name: TA.XT.plus TEXTURE ANALYSER (Stable Micro Systems Limited) This is the determined value.

[0126] The results are shown in Figure 8. As shown in Figure 8, Lens I, an ionic SHCL, was used. In this case, non-silicone soft contact lenses such as Lens III and Lens IV, and non- Compared to Lens II, an ionic SHCL, significantly higher pollen protein adsorption was observed. These results suggest that pollen proteins are ionic, even in soft contact lenses. There is a tendency for pollen proteins to adsorb in extremely large amounts to SHCL. It was confirmed that there is a unique problem in that it is highly susceptible to adsorbing carbon.

[0127] Test Example 6: Evaluation of the effect of ionic SHCL on the inhibition of pollen protein accumulation (1) Lens I (ionic S) in which significant adsorption of pollen proteins was confirmed in the above-mentioned Reference Test Example 3 The following tests were carried out using HCl.

[0128] First, the lenses I were immersed in 5 mL of physiological saline solution one by one and stored at room temperature for 5 hours. (Lens pretreatment). Pollen protein antigen (Cedar Pollen, manufactured by LSL Co., Ltd.) Extract-Ja, Properties: Lyophilized powder (Cedar Pollen crude extract Mountain ceder, Juniperus Asheii pollen) was dissolved in saline and 5mg / 50mL of pollen protein solution was obtained. A 1.0 mL sample of the pollen protein solution was placed in each well of a 24-well plate. After wiping off excess water from the lenses, they were immersed in the solution and shaken at 34°C and 400 rpm for 24 hours. I went there.

[0129] Lens I was taken out from the pollen protein solution and quickly placed in 100 mL of saline. After immersing the plate in water for about 1 second to rinse off excess liquid, wipe off the water and place the plate in a 24-well plate. 9. The test solution (Example 1, Comparative Examples 2-3, and Control) was immersed in 1.0 mL of each solution. The lens was then shaken at 34°C and 400 rpm for 18 hours. Quickly dip the beaker into 100 mL of saline solution (for about 1 second) to rinse off excess liquid, then rinse the beaker Using a 24-well plate, lightly drain the water and place in pollen protein isolation solution (1% carbonated The plate was immersed in 0.5 mL of an aqueous solution containing sodium and 1% SDS. The plate was rotated at 34°C and 400 rpm. The lens was shaken at 4°C for 3 hours, and the pollen proteins adsorbed on the lens were separated into the pollen protein separation solution. He made him do so.

[0130] In addition, by subtracting the effect of each test solution, the amount of pollen protein adsorption can be calculated more accurately. In order to detect the presence of pollen protein in the blank group, the process of treatment with the pollen protein solution was replaced with treatment with physiological saline. The treatment was the same as above, except that the treatment was changed to each test solution and pollen protein isolation solution. We prepared a sample that had undergone the above procedure.

[0131] Using the Micro BCA Assay Kit (Thermo Scientific, Pierce #23235), pollen The amount of pollen protein in the protein separation solution was quantified as an albumin equivalent value, and the lens The amount of pollen protein adsorbed to I was calculated. The absorbance of each sample was then subtracted from that of the blank group to obtain the albumin equivalent. The amount of pollen protein adsorption was calculated by the following formula: The amount of pollen protein adsorption when the test solution of Comparative Example and Example was used was compared. The pollen protein adsorption improvement rate (%) was calculated from the ratio of pollen protein adsorption amount when used. did.

[0132]

number

[0133] [Table 9]

[0134] The results are shown in FIG. 9. As a result, when sodium chondroitin sulfate was used alone (comparison Comparative Example 3) was found to have no effect of improving the adsorption of pollen proteins. Unexpectedly, this sodium chondroitin sulfate and flavin adenine dinucleotide When used in combination with sodium dodecyl sulfate (Example 1), the pollen protein adsorption improvement rate synergistically enhanced, effectively reducing the amount of pollen protein adsorbed to ionic SHCL It was revealed that this could suppress accumulation.

[0135] Test Example 7: Evaluation of the inhibition of pollen protein accumulation by ionic SHCL (2) Using the test liquids shown in Table 10 below, the ionic SHC We evaluated the effect of pollen proteins in improving the adsorption of L.

[0136] [Table 10]

[0137] The results are shown in FIG. 10. As shown in FIG. 10, pyridoxine hydrochloride, chondroitin sulfate Neither sodium aspartate nor potassium aspartate alone could inhibit the growth of pollen proteins. No effect of improving the adsorption of cellulose was observed (Comparative Examples 3, 5 and 6). In particular, sodium chondroitin sulfate or potassium aspartate and pyridoxyl hydrochloride By applying a specific combination of ionic SHCL, pollen protein adsorption was improved. Not only can it prevent the decline in adhesion rate, but it also synergistically binds pollen proteins to ionic SHCL. It was found that this method can reduce the amount of adsorption of pollen proteins and inhibit the accumulation of pollen proteins on ionic SHCL. (Examples 4 and 6).

[0138] Formulation examples The formulations shown in Table 11 were used for the SHCL eye drops (Examples 11-15) and SHCL application solution (Example Example 16), SHCL eye drop and eye drop (Example 17), SHCL eye wash (Example 18) , and SHCL cleaning solution (Examples 19-20) are prepared.

[0139] [Table 11]

Claims

[Claim 1] (A) Flavin adenine dinucleotide, pyridoxine, and salts thereof (B) at least one selected from the group consisting of chondroitin sulfate, aminoethylsulfonic acid, Contains at least one selected from the group consisting of aspartic acid and salts thereof. , Ophthalmic compositions for silicone hydrogel contact lenses.

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