JP2011132227A - Ophthalmic composition for use in silicone hydrogel contact lens - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an ophthalmic composition for use in silicone hydrogel contact lenses, which contains a terpenoid and is still capable of suppressing the adsorption of the terpenoid on the silicone hydrogel contact lens, even when applicable to the silicone hydrogel contact lens. <P>SOLUTION: The ophthalmic composition for use in silicone hydrogel contact lenses is prepared by using (A) the terpenoid in combination with (B) a vitamin E group. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an ophthalmic composition for a silicone hydrogel contact lens in which terpenoid adsorption to the silicone hydrogel contact lens is suppressed while containing the terpenoid. The present invention also relates to a method for suppressing adsorption of terpenoids to a silicone hydrogel contact lens. Furthermore, this invention relates to the method of suppressing lipid adsorption | suction to a nonionic silicone hydrogel contact lens. Still further, the present invention provides a method for reducing friction of an ionic silicone hydrogel contact lens, a method for suppressing the size expansion of a silicone hydrogel contact lens caused by a terpenoid, and adhesion of bacteria to the silicone hydrogel contact lens. It is related with the control method.

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

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

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

  In recent years, it has been reported that the surface of a silicone hydrogel contact lens has significant irregularities that are not found on the surface of a normal hydrogel contact lens (Non-Patent Document 2). Such prominent irregularities are not only easy to attach biological substances and dirt, but also cause increased friction compared to those with a smooth surface, especially in sensitive eye tissues. It is also possible to cause discomfort such as a feeling of foreign matter and dryness.

  In general, it is indispensable to design an ophthalmic composition used for a contact lens in consideration of safety and other effects depending on the type of contact lens. In particular, soft contact lenses vary in the presence or absence of ionicity and moisture content depending on the material, so ophthalmic compositions used for soft contact lenses should be formulated according to the characteristics of the target soft contact lens. Is essential.

  On the other hand, terpenoids have been used in ophthalmic compositions as a cooling agent for alleviating irritation and reducing discomfort or imparting a refreshing feeling or cooling feeling. And it is known that a terpenoid shows the tendency which becomes especially easy to adsorb | suck with respect to silicon hydrogel type SCL among SCL (patent document 1).

  Vitamin E has been used in ophthalmic compositions so far for the purpose of accelerating the metabolism of eye cells and relieving eye fatigue. However, an ophthalmic composition containing vitamin E applicable to SCL (including silicone hydrogel contact lenses) is difficult due to the difficulty in designing the formulation of the ophthalmic composition used in the soft contact lens as described above. It has not been marketed so far.

  And the effect at the time of combining vitamin E and terpenoid and applying to a silicone hydrogel contact lens is not known at all, and it is the present condition that it cannot be guessed at all.

International Publication No. WO2007 / 145344 Pamphlet

Hiroshi Shiotani, New Ophthalmology Vol.25, No.7, 907-912, 2008 Akemi Hariya et al., 51st Annual Meeting of the Japanese Contact Lens Society Program Abstracts, 110 pages

  As described above, silicone hydrogel contact lenses (hereinafter sometimes referred to as “SHCL”) are well known to adsorb terpenoids more easily than conventional hydrogel lenses. When a large amount of ophthalmic compound is adsorbed on SHCL, there is a concern about the effect of the adsorbed component remaining on the lens, and it may cause discoloration of the soft contact lens, decrease in light transmittance, deformation, etc. . Therefore, development of further useful means for effectively suppressing the adsorption of terpenoids on SHCL is required.

  As a result of diligent studies to solve the above problems, the present inventors have surprisingly found that (A) terpenoids and (B) vitamin E are used in combination to significantly absorb terpenoids on SHCL. It was found that it can be suppressed.

  In addition, the present inventors have further studied, and surprisingly, by combining (A) terpenoid and (B) vitamin E, it is possible to suppress lipid adsorption to nonionic SHCL. I found it. Furthermore, the inventors of the present invention have the lipid adsorption inhibitory effect on nonionic SHCL, in addition to the above components (A) and (B), further comprising (C) neostigmine, aminoethylsulfonic acid, and salts thereof. It has also been found that it can be further improved by using at least one selected from the group in combination.

  Furthermore, the present inventors can use (A) terpenoid and (B) vitamin E in combination to greatly reduce (i) friction of ionic SHCL, and (ii) bacteria to SHCL. It has been found that adhesion can also be suppressed.

  Furthermore, the present inventors can suppress the size expansion of SHCL caused by terpenoids by using (B) vitamin E in combination, and more effectively using neostigmine and / or a salt thereof in combination. It was also confirmed that it can be suppressed.

  The present invention has been completed by further studies based on this finding.

That is, the present invention provides the following ophthalmic compositions for SHCL.
Item 1-1. An ophthalmic composition for a silicone hydrogel contact lens, comprising (A) a terpenoid and (B) vitamin E.
Item 1-2. Item 1. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-1, which contains at least one selected from the group consisting of menthol and camphor as component (A).
Item 1-3. Item 1. The ophthalmic composition for a silicone hydrogel contact lens according to Item 1-1 or 1-2, wherein the component (A) is contained in a total amount of 0.00001 to 0.5 w / v%.
Item 1-4. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-3, which contains tocopherol acetate as the component (B).
Item 1-5. Item 5. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-4, wherein the component (B) is contained in a total amount of 0.0005 to 0.25 w / v%.
Item 1-6. The silicone hydrogel contact lens according to any one of Items 1-1 to 1-5, further comprising (C) at least one selected from the group consisting of neostigmine, aminoethylsulfonic acid, and salts thereof Ophthalmic composition.
Item 1-7. Item 5. The ophthalmic composition for a silicone hydrogel contact lens according to Item 1-6, which contains at least one selected from the group consisting of neostigmine methylsulfate and aminoethylsulfonic acid as component (C).
Item 1-8. Item 8. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-6 or 1-7, wherein the total amount of component (C) is 0.00005 to 2.5 w / v%.
Item 1-9. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-8, further comprising a surfactant.
Item 1-10. Item 10. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-9, which contains a nonionic surfactant as a surfactant.
Item 1-11. Item 10. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-10, which contains a total amount of surfactants of 0.001 to 1.0 w / v%.
Item 1-12. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-11, further comprising a buffer.
Item 1-13. Item 13. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-12, which contains a borate buffer as a buffer.
Item 1-14. Item 14. The ophthalmic composition for a silicone hydrogel contact lens according to Item 1-12 or 1-13, which contains a buffering agent in a total amount of 0.01 to 10 w / v%.
Item 1-15. Item 15. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-14, further comprising an isotonic agent.
Item 1-16. Item 15. The ophthalmology for silicone hydrogel contact lenses according to Item 1-15, which contains at least one selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerin, and propylene glycol as an isotonic agent. Composition.
Item 1-17. Item 15. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-15 or 1-16, which contains an isotonic agent in a total amount of 0.01 to 10 w / v%.
Item 1-18. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-17, which is an eye drop.
Item 1-19. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-18, which is used for ionic silicone hydrogel contact lenses.
Item 1-20. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-18, which is used for nonionic silicone hydrogel contact lenses.

The present invention also provides the following method for suppressing adsorption of terpenoids to SHCL.
Item 2. A method of suppressing adsorption of the component (A) to a silicone hydrogel contact lens, which comprises using (A) a terpenoid and (B) vitamin E in combination.

Moreover, this invention provides the method of providing the adsorption | suction suppression effect | action of the terpenoid to SHCL which is hung up below.
Item 3. (A) Ophthalmic composition for silicone hydrogel contact lens containing terpenoid, (B) Vitamin E is blended to suppress adsorption of component (A) to silicone hydrogel contact lens A method of imparting an action to the ophthalmic composition.

The present invention also provides the following agents for suppressing the adsorption of terpenoids to SHCL.
Item 4. (B) An agent for suppressing adsorption of terpenoids to a silicone hydrogel contact lens, containing vitamin E.

The present invention also provides a method for inhibiting the adsorption of lipids to nonionic SHCL.
Item 5. A nonionic silicone hydrogel characterized by contacting an ophthalmic composition for a silicone hydrogel contact lens containing (A) a terpenoid and (B) vitamin E with a nonionic silicone hydrogel contact lens A method of suppressing lipid adsorption to contact lenses.

Moreover, this invention provides the method of providing the effect | action which suppresses adsorption | suction of the lipid to the nonionic SHCL hung up below.
Item 6. Nonionic silicone hydrogel contact for ophthalmic composition for silicone hydrogel contact lens, characterized in that (A) terpenoid and (B) vitamin E are blended in ophthalmic composition for silicone hydrogel contact lens A method of imparting an action of suppressing the adsorption of lipid to a lens.

The present invention also provides a method for reducing the friction of ionic SHCL listed below.
Item 7. An ionic silicone hydrogel contact lens, characterized in that an ophthalmic composition for a silicone hydrogel contact lens containing (A) a terpenoid and (B) vitamin E is brought into contact with the ionic silicone hydrogel contact lens To reduce friction.

Moreover, this invention provides the method of providing the effect | action which reduces the friction of ionic SHCL hung up below.
Item 8. An ionic silicone hydrogel contact lens for an ophthalmic composition for silicone hydrogel contact lenses, characterized in that (A) a terpenoid and (B) vitamin E are blended in an ophthalmic composition for silicone hydrogel contact lenses A method of imparting an action of reducing friction of the steel.

Moreover, this invention provides the method of suppressing adhesion of the bacteria to SHCL hung up below.
Item 9. The ophthalmic composition for a silicone hydrogel contact lens containing (A) a terpenoid and (B) vitamin E is brought into contact with the silicone hydrogel contact lens. A method for suppressing adhesion.

Moreover, this invention provides the method of providing the effect | action which suppresses adhesion of the bacteria to SHCL hung up below.
Item 10. An ophthalmic composition for silicone hydrogel contact lenses, wherein (A) a terpenoid and (B) vitamin E are blended in an ophthalmic composition for silicone hydrogel contact lenses, A method of imparting an action of suppressing bacterial adhesion.

The present invention also provides the following methods for suppressing the size expansion of SHCL caused by terpenoids.
Item 11. A method for suppressing size expansion of a silicone hydrogel contact lens caused by a terpenoid, comprising using (A) a terpenoid and (B) vitamin E in combination.

Moreover, this invention provides the method of providing the effect | action which suppresses the size expansion of SHCL which arises by the terpenoid shown below.
Item 12. (A) A terpenoid-containing ophthalmic composition for silicone hydrogel contact lenses is blended with (B) vitamin E, and has the effect of suppressing the size expansion of silicone hydrogel contact lenses caused by terpenoids. A method of applying to an ophthalmic composition.

The present invention also provides the following agents for suppressing the size expansion of SHCL caused by terpenoids.
Item 13. (B) An agent for suppressing size expansion of a silicone hydrogel contact lens produced by a terpenoid, containing vitamin E.

  According to the ophthalmic composition for SHCL of the present invention, it is possible to effectively suppress the component from adsorbing to SHCL while containing a terpenoid. Therefore, the ophthalmic composition for SHCL of the present invention makes it possible to use SHCL more comfortably and safely without causing any fear of lens deformation or discoloration caused by adsorption of terpenoids to SHCL.

  Furthermore, the ophthalmic composition for SHCL of the present invention can remarkably suppress lipid adsorption to nonionic SHCL. Therefore, according to the ophthalmic composition for SHCL of the present invention, lipid contamination of nonionic SHCL can be prevented, clouding of nonionic SHCL, etc. can be prevented, and the original vision correction power of nonionic SHCL can be maintained. Furthermore, it is possible to effectively prevent corneal epithelial damage such as corneal staining caused by lipid adsorption to nonionic SHCL, and to use nonionic SHCL comfortably and safely.

  Furthermore, the present inventors have confirmed that ionic SHCL has significantly large friction. This can cause discomfort (foreign material feeling, dry feeling, etc.), eye fatigue, and the like when using ionic SHCL. Furthermore, a contact lens with high friction may cause epithelial damage to the keratoconjunctiva when the mucous membrane on the back side of the eyelid and the contact lens surface rub against each other or whenever the contact lens moves on the eyeball surface. On the other hand, according to the present invention, the friction on the surface of the ionic SHCL can be remarkably suppressed, so that discomfort and fatigue of the eye when wearing the ionic SHCL can be reduced, and keratoconjunctival epithelial disorder can be prevented. It is possible to prevent and use ionic SHCL comfortably and safely.

  In addition, SHCL has a great merit that it can supply a sufficient amount of oxygen to the cornea, but it also has the disadvantage that conjunctival bacteria tend to adhere (MDP Willcox et al., Bacterial interactions with contact lenses; effects of lens material, lens wear and microbial physiology, Biomaterials 22 (2001), 3235-3247). Many conjunctival resident bacteria are non-pathogenic, but if excessive adhesion or proliferation occurs, a biofilm is formed on the surface of SHCL by extracellular substances secreted from the attached / proliferated bacteria, causing pathogenicity. There is a danger of becoming a hotbed of microorganisms. Furthermore, since SHCL has a high oxygen permeability, it may be worn continuously for up to 1 month, so it can be said that it tends to promote bacterial adhesion during wearing, which is one of the risk factors for bacterial infections. It is also pointed out. On the other hand, according to the ophthalmic composition for SHCL of the present invention, since bacterial adhesion to SHCL can be suppressed, the growth of pathogenic microorganisms can be suppressed, and bacterial infection can be achieved even with long-term SHCL wearing. The risk of this can be reduced and SHCL can be used safely.

  Furthermore, according to the ophthalmic composition for SHCL of the present invention, it is possible to suppress the expansion of the size of the SHCL while containing the terpenoid, and the SHCL can be used more comfortably and safely.

In Test Example 1, it is a figure which shows the result of having measured the adsorption amount of the menthol to SHCL using the test liquid (Example 1 and Comparative Example 1). In Test Example 2, it is a figure which shows the result of having measured the adsorption amount of the menthol to SHCL using the test liquid (Example 2 and Comparative Example 2). In Experiment 3, it is a figure which shows the result of having measured the adsorption amount of the camphor to SHCL using the test liquid (Example 1-2 and Comparative Example 1-2). In reference test example 1, it is a figure which shows the result of having evaluated the adsorption | suction characteristic of the lipid in various soft contact lenses. In Test Example 4, it is a figure which shows the result of having evaluated the influence which acts on adsorption | suction of the lipid to nonionic SHCL about a test liquid (Example 3-5 and Comparative Example 3-9). In Test Example 5, it is a figure which shows the result of having evaluated the reduction effect with respect to the friction of an ionic SHCL surface about a test liquid (Example 6 and Comparative Example 10). In Test Example 6, it is a figure which shows the result of having evaluated the effect which suppresses the bacteria adhesion to SHCL about a test liquid (Example 7 and Comparative Examples 11-13). In Test Example 7, it is a figure which shows the result of having evaluated the effect which suppresses the bacteria adhesion to SHCL and a non-silicone hydrogel lens about a test liquid (Example 8 and Comparative Example 14).

1. The ophthalmic composition for SHCL The ophthalmic composition for SHCL of the present invention contains a terpenoid (hereinafter also referred to as component (A)).

  Terpenoids are known compounds that have a structure having isoprene units as structural units and are widely used as cooling agents.

  The terpenoid is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of terpenoids include menthol, menthone, camphor, borneol, geraniol, cineole, citronellol, carvone, anethole, eugenol, limonene, linalool, linalyl acetate, and derivatives thereof. These compounds may be d-form, l-form or dl-form. In the present invention, an essential oil containing the above compound may be used as a terpenoid. Examples of such essential oils include eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, rose oil, camphor oil and the like. These terpenoids may be used alone or in any combination of two or more.

  Among these terpenoids, menthol, menthone, camphor, borneol and geraniol are preferable, and examples of the essential oil containing these include cool mint oil, peppermint oil, peppermint oil, camphor oil, and rose oil. More preferred are menthol and camphor, more preferably l-menthol, dl-menthol, d-camphor and dl-camphor, and particularly preferred are l-menthol and d-camphor. Examples include cool mint oil, peppermint oil, mint oil, camphor oil and the like.

  In the ophthalmic composition for SHCL of the present invention, the blending ratio of the component (A) may be appropriately set according to the type of the component (A), the formulation form of the ophthalmic composition for SHCL, etc. The total amount of the component (A) is 0.00001 to 0.5 w / v%, preferably 0.0001 to 0.15 w / v%, more preferably 0.001 to 0.05 w / v%, based on the total amount of the ophthalmic composition. . In addition, when using the essential oil containing a terpenoid as (A) component, the terpenoid content in the essential oil mix | blended is set so that the said mixture ratio may be satisfy | filled.

  The ophthalmic composition for SHCL of the present invention contains vitamin E (hereinafter also referred to as (B) component) in addition to the above component (A). By containing the component (B) together with the component (A) in this way, it becomes possible to suppress the adsorption of the component (A) to SHCL. Also, by combining these components, lipid adsorption suppression action to nonionic SHCL, friction reduction action to ionic SHCL, action to suppress bacterial adhesion to SHCL, or SHCL size expansion caused by component (A) It is also possible to provide an action of suppressing the above.

  Vitamin E is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. Specifically, tocopherol, tocotrienol, and derivatives thereof, and these Salt. The tocopherol and tocotrienol may be any of α-, β-, γ-, and δ-, and may be either d-form or dl-form. Tocopherol is preferable, α-tocopherol is more preferable, and dl-α-tocopherol is still more preferable.

  Examples of tocopherol derivatives include tocopherol organic acid esters such as tocopherol acetate, tocopherol succinate, tocopherol nicotinate and tocopherol linolenate. One of these derivatives may be selected and used alone, or two or more may be used in any combination.

  The salt of tocopherol, tocotrienol and derivatives thereof is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. Specifically, a salt with an organic base ( For example, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), salts with inorganic bases [for example, ammonium salts; alkali metals (sodium, potassium, etc.), Alkaline earth metals (calcium, magnesium, etc.), salts with metals such as aluminum, etc.]. Tocopherol, tocotrienol and salts of these derivatives may be used alone by selecting one kind, or two or more kinds may be used in any combination.

  In the ophthalmic composition for SHCL of the present invention, component (B) may be used alone or in combination of two or more of tocopherol, tocotrienol, and derivatives thereof, and salts thereof. May be used in any combination. From the viewpoint of further improving the adsorption suppressing action of the component (A) on SHCL, the component (B) is preferably tocopherol, a derivative thereof, and a salt thereof, more preferably a derivative of tocopherol, still more preferably a tocopherol organic. An acid ester, particularly preferably tocopherol acetate is used. In addition, the component (B) exemplified here effectively suppresses the adsorption of lipids to nonionic SHCL, effectively reduces friction of ionic SHCL, and effectively attaches bacteria to SHCL. It is also suitable from the viewpoint of suppressing or suppressing the SHCL size expansion caused by the component (A).

  In the ophthalmic composition for SHCL of the present invention, the blending ratio of component (B) is appropriately set according to the type of component (A), the type of component (B), the formulation form of the ophthalmic composition for SHCL, etc. However, as an example, with respect to the total amount of the ophthalmic composition for SHCL, the total amount of component (B) is 0.0005 to 0.25 w / v%, preferably 0.001 to 0.15 w / v%, more preferably 0.005 to 0.1 w. / v% is exemplified.

  Further, in the ophthalmic composition for SHCL of the present invention, the ratio of the component (B) to the component (A) is not particularly limited, but the adsorption of the component (A) to the SHCL is more effectively suppressed. From the viewpoint of, the range in which the total amount of the component (B) is 0.1 to 250,000 parts by weight, preferably 1 to 150,000 parts by weight, more preferably 10 to 5000 parts by weight per 100 parts by weight of the total amount of the component (A). Illustrated. In addition, when using the essential oil containing a terpenoid as (A) component, the terpenoid content in the essential oil mix | blended is set so that the said ratio may be satisfy | filled. In addition, by satisfying the above ratio, it is possible to more effectively suppress lipid adsorption to nonionic SHCL, more effectively reduce friction of ionic SHCL, and more effectively suppress bacterial adhesion to SHCL. It is also possible to more effectively suppress the size expansion of SHCL caused by terpenoids.

  In addition to the above components (A) and (B), the ophthalmic composition for SHCL of the present invention further comprises (C) at least one selected from the group consisting of neostigmine, aminoethylsulfonic acid, and salts thereof. (Hereinafter sometimes simply referred to as the component (C)). Thus, by further including the component (C), it is possible to further improve the lipid adsorption inhibiting action on nonionic SHCL. Further, by further containing the component (C) as described above, it is possible to further improve the effect of inhibiting bacterial adhesion to SHCL, or to more effectively suppress the size expansion of SHCL by terpenoids.

  Among the components (C), neostigmine is a compound also called N-(-3-dimethylcarbamoyloxyphenyl) -N, N, N-trimethylammonium. Neostigmine and its salt are known compounds as an eye focus control function improving agent, and may be synthesized by a known method or obtained as a commercial product.

  The salt of neostigmine is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. Specifically, methylsulfate (methylsulphate neostigmine), bromide salt (Neostigmine bromide) and the like are exemplified. Among these salts, methyl sulfate is preferable. These neostigmine salts may be used alone or in any combination of two or more.

  Among neostigmine and its salts, from the viewpoint of further enhancing the lipid adsorption inhibitory action on nonionic SHCL, or from the viewpoint of more effectively suppressing the lens size expansion of SHCL caused by terpenoids, preferably a neostigmine salt, Preferably, neostigmine methyl sulfate is used.

  Of the component (C), aminoethylsulfonic acid is a known compound also called taurine.

  The salt of aminoethylsulfonic acid is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. As a salt of aminoethylsulfonic acid, specifically, a salt with an organic base (for example, a salt with an organic amine such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), inorganic Salts with bases [for example, ammonium salts; alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), salts with metals such as aluminum, etc.] and the like. These aminoethylsulfonic acid salts may be used alone or in any combination of two or more.

  Among aminoethylsulfonic acids and salts thereof, aminoethylsulfonic acid is preferred from the viewpoint of further enhancing the lipid adsorption inhibiting action on nonionic SHCL, or from the viewpoint of more effectively suppressing bacterial adhesion to SHCL. It is done.

  In the ophthalmic composition for SHCL of the present invention, as the component (C), one kind of neostigmine, aminoethylsulfonic acid, and salts thereof may be used alone, or two or more kinds thereof may be used. Although they may be used in any combination, at least one selected from the group consisting of neostigmine and its salts is preferable from the viewpoint of more effectively suppressing the expansion of the lens size of SHCL caused by terpenoids. From the viewpoint of more effectively suppressing bacterial adhesion, at least one selected from the group consisting of aminoethylsulfonic acid and salts thereof is preferable. Preferable examples of the component (C) used in the present invention include neostigmine methyl sulfate and aminoethyl sulfonic acid.

When the component (C) is blended in the SHCL ophthalmic composition of the present invention, the blending ratio of the component (C) is the type of the component (C), the type and amount of the other blended components, and the SHCL ophthalmology. It can set suitably according to the formulation form etc. of a composition. As an example of the blending ratio of the component (C), the total amount of the component (C) is 0.00005 to 2.5 w / v%, preferably 0.001 to 1.5 w / v% with respect to the total amount of the ophthalmic composition for SHCL. Is done. More specifically, the following ranges are exemplified as the blending ratio of each component (C) with respect to the total amount of the ophthalmic composition for SHCL.
When component (C) is neostigmine and / or a salt thereof: these are generally 0.00005 to 0.025 w / v%, preferably 0.0001 to 0.015 w / v%, more preferably 0.001 to 0.01 w / v% in total amount;
When component (C) is aminoethylsulfonic acid and / or a salt thereof: These are generally in a total amount of 0.01 to 2.5 w / v%, preferably 0.05 to 2 w / v%, more preferably 0.1 to 1.5 w / v%. .

Further, in the ophthalmic composition for SHCL of the present invention, the ratio of the component (C) to the component (A) is not particularly limited, but the viewpoint of further enhancing the lipid adsorption inhibiting action on the nonionic SHCL. From the viewpoint of more effectively suppressing bacterial adhesion to SHCL, or from the viewpoint of more effectively suppressing the size expansion of SHCL caused by terpenoids, per 100 parts by weight of the total amount of (A) component, Examples include a range in which the total amount is 0.01 to 200000 parts by weight, preferably 2 to 100000 parts by weight. More specifically, the following ranges are exemplified as the ratio of each component (C) per 100 parts by weight of the total amount of component (A):
When component (C) is neostigmine and / or a salt thereof: these are total amounts, usually 0.01 to 25000 parts by weight, preferably 0.1 to 15000 parts by weight, more preferably 2 to 500 parts by weight;
When component (C) is aminoethylsulfonic acid and / or a salt thereof: these are generally 2 to 200000 parts by weight, preferably 35 to 150,000 parts by weight, and more preferably 200 to 100,000 parts by weight.

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

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

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

  Among the above surfactants, preferably nonionic surfactants; more preferably POE sorbitan fatty acid esters, POE hydrogenated castor oil, POE / POP block copolymers; more preferably POE sorbitan fatty acid esters, POE cured Castor oil is used.

  When a surfactant is blended in the ophthalmic composition for SHCL of the present invention, the blending ratio of the surfactant is the type of the surfactant, the type and amount of other blended components, the ophthalmic composition for SHCL. It can set suitably according to a formulation form etc. As an example of the blending ratio of the surfactant, the total amount of the surfactant is 0.001 to 1.0 w / v%, preferably 0.005 to 0.7 w / relative to the total amount of the ophthalmic composition for SHCL. An example is v%, more preferably 0.01 to 0.5 w / v%.

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

  When a buffering agent is blended with the ophthalmic composition for SHCL of the present invention, the blending ratio of the buffering agent depends on the type of buffering agent used, the type and amount of other blending components, the formulation form of the ophthalmic composition, etc. Depending on the total amount of the ophthalmic composition for SHCL, for example, the total amount of the buffer is 0.01 to 10 w / v%, preferably 0.1 to 5 w / Examples are v%, more preferably 0.5 to 2 w / v%.

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

  When an isotonic agent is blended in the ophthalmic composition for SHCL of the present invention, the blending ratio of the tonicity agent varies depending on the type of tonicity agent used and cannot be defined uniformly. However, for example, the proportion of the tonicity agent is 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%, more preferably 0.1 to 3 w / v% in the total amount. .

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

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

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

In addition, in the ophthalmic composition for SHCL of the present invention, various additives are appropriately selected according to a conventional method according to its use and form as long as they do not impair the effects of the invention, and one or more of them are selected. An appropriate amount may be contained in combination. Examples of these additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Carrier: An aqueous carrier such as water or hydrous ethanol.
Thickeners: for example, carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, alginic acid, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol and the like.
Sugars: For example, cyclodextrins and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.
Preservatives, bactericides or antibacterials: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, etc.), glowul (manufactured by Rhodia) Name) etc.
pH adjuster: for example, hydrochloric acid, boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, boro Sand, triethanolamine, monoethanolamine, diisopropanolamine, sulfuric acid, phosphoric acid, polyphosphoric acid, propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, gluconolactone, ammonium acetate etc.
Stabilizer: For example, dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate and the like.
Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), and the like.

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

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

  The ophthalmic composition for SHCL of the present invention is not limited in its formulation form as long as it is used in the ophthalmic field and is used so as to come into contact with SHCL. For example, eye drops for SHCL (eye drops that can be used while wearing SHCL), eye drops for SHCL (eye wash that can be used while wearing SHCL), SHCL wearing liquid, SHCL care liquid (SHCL disinfectant, SHCL Storage solution, SHCL cleaning solution, SHCL cleaning storage solution, etc.).

  Among these, the eye drops for SHCL are preparations that are generally used more frequently than other ophthalmic compositions, and the above-mentioned (A) component is likely to be adsorbed in large amounts on SHCL. There is a tendency to cause SHCL size expansion. According to the present invention, it is possible to effectively suppress the adsorption of the component (A) and to effectively suppress the size expansion even in such an eye drop that easily adsorbs the component (A). In addition, since the eye drops for SHCL can be used easily during SHCL wearing, it is possible to effectively prevent lipid stains from attaching during SHCL wearing, and to prevent uncomfortable feeling during SHCL wearing and to wear SHCL comfortably This is preferable in that it can be performed. In addition, eye drops for SHCL can be used easily when you feel discomfort or eye fatigue due to friction of the lens while wearing ionic SHCL, and also when you are wearing SHCL continuously for a long time. It is also suitable from the viewpoint that it can be easily used to suppress bacterial adhesion. In view of these viewpoints, a preferred example of the ophthalmic composition for SHCL of the present invention is an eye drop for SHCL.

  The method for using the ophthalmic composition for SHCL of the present invention is not particularly limited as long as it is a known method having a step of bringing the ophthalmic composition for SHCL into contact with SHCL. For example, in the case of SHCL eye drops, an appropriate amount of the eye drops may be instilled before or during the wearing of SHCL. Further, in the case of an eye wash for SHCL, an appropriate amount of the eye wash may be used for eye washing before or during wearing of SHCL. In addition, when the ophthalmic composition for SHCL of the present invention is an eye drop for SHCL or an eye wash for SHCL, it can be used for the purpose of eye drops or eye wash even when not wearing SHCL. it can. Moreover, in the case of SHCL mounting liquid, it is used by contacting SHCL with an appropriate amount of the mounting liquid when SHCL is mounted. Furthermore, in the case of an SHCL care solution, it is used by immersing SHCL in an appropriate amount of the care solution, or by bringing SHCL into contact with the care solution and scrubbing.

  In the ophthalmic composition for SHCL of the present invention, the type of SHCL to be applied is not particularly limited, and any SHCL that is currently marketed or will be marketed in the future regardless of whether it is ionic or nonionic. Can be applied. In particular, ionic SHCL has been recognized to have a strong property of adsorbing terpenoids, but according to the ophthalmic composition for SHCL of the present invention, terpenoids can easily be adsorbed to ionic SHCL. Adsorption can be effectively suppressed. Moreover, according to the ophthalmic composition for SHCL of the present invention, the friction of ionic SHCL can be effectively reduced. In view of this viewpoint, ionic SHCL can be mentioned as an example of a suitable application target of the ophthalmic composition for SHCL of the present invention. From another point of view, the non-ionic SHCL has a specific problem that the lipid is remarkably easily adsorbed. However, according to the ophthalmic composition for SHCL of the present invention, not only the adsorption suppression of terpenoids but also the above. Lipid adsorption to nonionic SHCL can also be effectively suppressed. In view of the effects of the present invention, non-ionic SHCL can be mentioned as an example of a suitable application target of the ophthalmic composition for SHCL of the present invention. Here, ionic is in accordance with US FDA (US Food and Drug Administration) standards, the ionic component content in contact lens material is 1 mol% or more, and non-ionic is in accordance with US FDA standards, This means that the ionic component content in the contact lens material is less than 1 mol%.

  Further, the moisture content of SHCL to be applied is not particularly limited, and examples thereof include 90% or less, preferably 60% or less, and more preferably 50% or less. Since SHCL contains a hydrogel material, it contains at least more than 0% moisture.

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

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

  In general, SHCL, which is harder than non-silicone hydrogel contact lenses, which have a softer material, tends to cause a deterioration in the feeling of use due to deformation of the lens due to the adsorption of foreign matter, etc., and tends to cause ocular mucosal damage. According to the ophthalmic composition for SHCL of the present invention, it is possible to effectively suppress the adsorption of the component (A) and the adsorption of lipid to the hard material SHCL that easily causes a deterioration in feeling of use and ocular mucosa, Thereby, deformation and alteration of the lens can be prevented, and deterioration of feeling of use and ocular mucosal damage can be effectively prevented. In view of the effects of the present invention, SHCL having a relatively high hardness can be cited as a suitable application target of the ophthalmic composition for SHCL of the present invention. Preferably, the hardness of SHCL to be applied is 3 g or more, preferably 4 g or more, more preferably 6 g or more, and still more preferably 8 g or more when measured by the following measuring method using a texture analyzer. Further, the upper limit value of the hardness of the SHCL to be applied is not particularly limited, but is preferably 15 g or less, more preferably 12 g or less.

  The hardness of the contact lens can be specifically measured as follows using a texture analyzer (product name: TA.XT.plus TEXTURE ANALYSER (manufactured by Stable Micro Systems Limited)).

  First, remove the contact lens to be measured from the package, wipe off excess water, rinse with physiological saline (0.9% sodium chloride solution), and then raise the convex surface on the bottom of the plastic petri dish filled with physiological saline. Arrange so that Next, the contact lens is adjusted to be directly below the probe of the measuring instrument, and measurement is performed under the following measurement conditions.

[Measurement condition]
Instrument settings:
Test mode Compression measurement Probe type φ10mm cylinder probe
Target Mode Distance
Distance 2.5mm
Triger Type Auto
Triger Force 0.1g
Test Speed 1.0mm / sec
Measure the stress when crushing the lens 2.5mm (2.5 seconds) after the probe starts to push down the lens apex, and record the maximum value as hardness.

  The ophthalmic composition for SHCL of the present invention can exhibit intrinsic physiological activity based on the above components (A) and (B) and can be used for various applications. For example, based on the component (A) or the component (B), it can be used for applications such as imparting a refreshing feeling, improving eyestrain, improving eyestrain.

  Moreover, the ophthalmic composition for SHCL of the present invention can effectively prevent corneal epithelial disorders such as corneal staining caused by lipid adsorption to nonionic SHCL, and thus prevent such corneal epithelial disorders. It can also be used as an agent.

  Moreover, since it has been found that SHCL easily adheres to bacteria and can be continuously worn for a long period of time, it may be used in a form of use in which adhesion of bacteria is easily promoted during wearing. On the other hand, according to the present invention, since bacterial adhesion to SHCL can be effectively suppressed, it can also be used as a preventive or alleviating agent for bacterial infections of the ocular mucosa.

2. Method for inhibiting adsorption of terpenoids to SHCL, method for imparting adsorption inhibition of terpenoids to SHCL, and agent for inhibiting adsorption of terpenoids to SHCL As described above, the above-mentioned component (A) on SHCL Adsorption can be suppressed by the component (B).

  Accordingly, the present invention provides a method for suppressing the adsorption of the component (A) to SHCL, characterized by using (A) a terpenoid and (B) vitamin E in combination from another viewpoint. . Further, the present invention is characterized in that (A) a terpenoid-containing ophthalmic composition for SHCL is blended with (B) vitamin E, and has the action of suppressing the adsorption of the (A) component to SHCL. A method of applying to the ophthalmic composition is also provided.

  The present invention also provides an agent for suppressing adsorption of terpenoids to SHCL, which contains (B) vitamin E.

  In these methods and agents, the types and proportions of components (A) and (B), the types and proportions of other components, the formulation form of the ophthalmic composition for SHCL, the types of SHCL to be applied, etc. The same as “1. Ophthalmic composition for SHCL”.

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

  Therefore, the present invention, from yet another viewpoint, is characterized in that an ophthalmic composition for SHCL containing (A) a terpenoid and (B) vitamin E is brought into contact with nonionic SHCL. Provided is a method for suppressing the adsorption of lipid to sex SHCL. Furthermore, the ophthalmic composition for SHCL contains (A) a terpenoid and (B) vitamin E, and the ophthalmic composition for SHCL suppresses lipid adsorption to nonionic SHCL. A method of imparting an action is provided.

  In these methods, the types and mixing ratios of the components (A) and (B), the types and mixing ratios of the other components to be mixed, the dosage form of the ophthalmic composition for SHCL, and the types of nonionic SHCL to be applied The same as in “1. SHCL ophthalmic composition”.

4). Method of reducing friction of ionic SHCL, and method of imparting action of reducing friction of ionic SHCL As described above, by using together the above components (A) and (B), friction of ionic SHCL is reduced. can do.

  Therefore, the present invention, from yet another point of view, is characterized in that an ophthalmic composition for SHCL containing (A) a terpenoid and (B) vitamin E is brought into contact with ionic SHCL. A method for reducing the friction of the resin is provided. Furthermore, the ophthalmic composition for SHCL is characterized in that (A) a terpenoid and (B) vitamin E are blended, and the ophthalmic composition for SHCL is imparted with an action to reduce friction of ionic SHCL. Provide a method.

  In these methods, the types and blending ratios of components (A) and (B), the types and blending ratios of other components to be blended, the formulation form of the ophthalmic composition for SHCL, the types of ionic SHCL to be applied, etc. Is the same as “1. Ophthalmic composition for SHCL”.

5. Method for inhibiting bacterial adhesion to SHCL, and method for imparting action to inhibit bacterial adhesion to SHCL As described above, by combining the above components (A) and (B), Adhesion can be suppressed.

  Therefore, the present invention, from yet another point of view, is characterized in that an ophthalmic composition for SHCL containing (A) a terpenoid and (B) vitamin E is brought into contact with SHCL. A method for suppressing adhesion is provided. Furthermore, the ophthalmic composition for SHCL is characterized by containing (A) terpenoid and (B) vitamin E in the ophthalmic composition for SHCL. Provide a way to grant.

  In these methods, the types and blending ratios of the components (A) and (B), the types and blending ratios of other components to be blended, the formulation form of the ophthalmic composition for SHCL, the types of SHCL to be applied, etc. The same as “1. Ophthalmic composition for SHCL”.

6). Method for suppressing size expansion of SHCL caused by terpenoid, method for imparting action for suppressing size expansion of SHCL caused by terpenoid, and agent for suppressing size expansion of SHCL caused by terpenoid As described above, (A) In addition, the combined use of component (B) can suppress the size expansion of SHCL caused by terpenoids.

  Therefore, the present invention provides a method for suppressing the size expansion of SHCL caused by the component (A), characterized in that (A) a terpenoid and (B) vitamin E are used in combination from another viewpoint. provide. Furthermore, (A) the ophthalmic composition for SHCL containing a terpenoid is blended with (B) vitamin E, and the action of suppressing the size expansion of SHCL caused by the component (A) A method of applying to a composition is provided.

  The present invention also provides an agent for suppressing the size expansion of SHCL caused by terpenoids, which contains (B) vitamin E.

  In these methods and agents, the types and mixing ratios of components (A) and (B), the types and mixing ratios of other components to be mixed, the dosage form of the ophthalmic composition for SHCL, the types of SHCL to be applied, etc. Is the same as “1. Ophthalmic composition for SHCL”.

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

Test Example 1: Menthol adsorption suppression test (1)
Using three types of SHCL described in Table 1 below, the amount of menthol adsorbed was evaluated.

  The hardness of each soft contact lens is a value measured using a texture analyzer (product name: TA.XT.plus TEXTURE ANALYSER (manufactured by Stable Micro Systems Limited)) as described above.

  First, three types of SHCL shown in Table 1 were immersed one by one in 5 mL of physiological saline (0.9 w / v% sodium chloride) and allowed to stand for 72 hours (lens pretreatment). Test solutions (Example 1 and Comparative Example 1) were prepared according to Table 2 below, and each test solution was filled in a 10 mL capacity headspace vial with high hermeticity by 10 mL. Each SHCL after pretreatment was immersed in these test solutions and subjected to a shaking treatment at 34 ° C. and 120 times / min for 24 hours (sample group). Moreover, the vial of each test solution which does not immerse SHCL as a blank group was provided, and the same shaking process as the sample group was performed. After pulling up the SHCL from the vial of each sample group, the amount of menthol in each test solution of the sample group and the blank group was quantified using gas chromatography according to a conventional method. By subtracting the menthol amount of the sample group from the menthol amount of the blank group, the menthol adsorption amount to SHCL in each test solution was calculated.

  The results are shown in FIG. As shown in FIG. 1, when the test solution of Comparative Example 1 was used, a large amount of menthol was observed in any of the three types of SHCL. In particular, it was recognized that a large amount of menthol tends to be adsorbed to the lens 1 which is ionic SHCL. On the other hand, when the test liquid (Example 1) which mix | blended the tocopherol acetate with the terpenoid (menthol and camphor) was used, it became clear that adsorption | suction of menthol can be suppressed with respect to any SHCL of the lenses 1-3. It was.

  When cyanocobalamin (a kind of vitamin B12) or flavin adenine dinucleotide sodium (a kind of vitamin B2) is used instead of tocopherol acetate, such menthol adsorption to SHCL No effect was observed (data not shown). Therefore, it has been clarified that the effect of suppressing the adsorption of menthol to SHCL is a specific effect that is specifically exhibited when tocopherol acetate is used.

Test Example 2: Menthol adsorption suppression test (2)
As the SHCL, using the lens 1 (ionic SHCL) in which particularly high menthol adsorption was observed in Test Example 1, the test solutions described in Table 3 below (Example 2 and Comparative Example 2) were tested. The amount of menthol adsorbed on SHCL was evaluated by the same method as in 1.

  The result is shown in FIG. As shown in FIG. 2, even when the type of nonionic surfactant used as a solubilizing agent for solubilizing terpenoids is changed, by using tocopherol acetate as in Test Example 1, SHCL is used. It was revealed that the adsorption of menthol on the surface can be suppressed.

Test Example 3: Camphor Adsorption Suppression Test For camphor, in order to confirm whether or not the same SHCL adsorption suppression effect as menthol can be obtained, in Test Examples 1 and 2 above, the lens 1 after immersing the SHCL (ionic) The amount of camphor in each test solution of SHCL) and the amount of camphor in each test solution in the blank group were measured by gas chromatography, and the amount of camphor adsorbed on lens 1 was also evaluated.

  The result is shown in FIG. As shown in FIG. 3, it has become clear that camphor also has an SHCL adsorption inhibitory effect by using tocopherol acetate (Example 1-2), and the adsorption inhibitory effect by tocopherol acetate is less than that of any terpenoid. It became clear that it was played.

Reference Test Example 1: Evaluation of Lipid Adsorption of Various Soft Contact Lenses The following experiments were conducted using the various soft contact lenses shown in Table 4 to evaluate the lipid adsorption properties of the soft contact lenses. The soft contact lenses used in this test are all commercially available products.

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

  The results are shown in FIG. As is clear from FIG. 4, the lipid adsorption amount of nonionic SHCL (lenses A and B) is significantly larger than that of ionic SHCL (lens C) and conventional hydrogel lenses (lenses D to F). It was confirmed that the problem of lipid contamination was serious.

Test Example 4: Nonionic SHCL Lipid Adsorption Inhibition Evaluation Using each of the test solutions shown in Table 5 below using the nonionic SHCL (Lens A) in which significant lipid adsorption was observed in Reference Test Example 1 above, The effect of nonionic SHCL on lipid adsorption was investigated.

  First, a 1 mg / ml chloroform solution of methanol (N- (fluorescein-5-thiocarbamoyl) -1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt; manufactured by invitrogen) and methanol is used 1: A physiological saline solution (0.9 w / v% sodium chloride) was added to 500 μL of the mixed solution mixed at a volume ratio of 4, and a total volume of 20 ml was prepared as a fluorescent lipid solution. Lens A was immersed in physiological saline for one night or longer and pre-test treatment was performed.

  Next, 1000 μL of each test solution (Example 3-5 and Comparative Example 3-9) is placed in each well of a 24-well microplate, and the lens A that has undergone pre-test treatment is immersed therein one by one. A shaking treatment was performed at 34 ° C. for 24 hours. The lens A that had been shaken was transferred to a 24-well microplate containing 1000 μL of the fluorescent lipid solution, and again shaken at 34 ° C. for 24 hours (sample group). Further, as a blank group, wells containing 1000 μL of physiological saline were prepared, and the lens A treated with each test solution was immersed one by one in the same manner and subjected to shaking treatment in the same manner. After 24 hours, each lens A after the shaking treatment was transferred to a plate containing 1 ml of new physiological saline, and the fluorescence intensity of each well was measured using a fluorescence plate reader (Thermo Fisher Scientific Inc.) ( Excitation wavelength: 485 nm, fluorescence wavelength: 538 nm). A value obtained by subtracting the fluorescence intensity of the blank group from the fluorescence intensity of each sample group was determined as an index of the amount of adsorbed lipid, and the value of each test solution was calculated when the control (Comparative Example 3) was 100%.

  The result is shown in FIG. As shown in FIG. 5, when menthol and tocopherol acetate were each used alone, it was recognized that there was little or no lipid adsorption inhibitory effect compared to the control (Comparative Examples 4 and 5). On the other hand, unexpectedly, it was shown that when menthol and tocopherol acetate were used in combination, lipid adsorption to nonionic SHCL could be synergistically suppressed (Example 3). Furthermore, neostigmine methylsulfate and aminoethylsulfonic acid itself have little or no lipid adsorption inhibiting effect (Comparative Examples 6 and 7), and when these components are combined with menthol, almost no lipid adsorption inhibiting effect is observed. Although there was no (Comparative Examples 8 and 9), when these components were used in combination with menthol and tocopherol acetate, it was also revealed that the lipid adsorption inhibitory effect can be dramatically improved (Examples). 4 and 5).

Reference test example 2: Evaluation of friction on ionic SHCL surface In order to measure the physical properties of the ionic SHCL surface, various surface property changes such as tackiness, viscoelasticity, drying property, etc. should be evaluated in terms of frictional increase / decrease. The friction force of the ionic SHCL surface was evaluated using a rigid pendulum physical property tester RPT-3000W (manufactured by A & D Co., Ltd.). The ionic SHCL used for the test is a lens I (ionic SHCL, main constituent monomer: TrisVC, NVP (USAN: Balafilcon A), water content 36.0%, BC 8.6, DIA 14.0 mm), which is a commercial product.

  This ionic SHCL immersed in physiological saline overnight was used as a test sample. The measurement is performed under the conditions of a temperature of 25 ° C. and a relative humidity of 60%, a pendulum weight of 200 g, a sensor diameter of 4 mm, and a logarithmic decay rate 5 minutes after the start of measurement. The friction was evaluated.

  The logarithmic decay rate measured here indicates the magnitude of the friction on the lens surface, and the higher the logarithmic decay rate, the greater the friction. As a result of measuring with respect to the lens I, the logarithmic decay rate was a remarkably high value of about 0.23. Accordingly, ionic SHCL was found to have a high logarithmic decay rate and very high friction.

Test Example 5: Evaluation of Reduction Effect on Friction of Ionic SHCL Surface Using the lens I used in Reference Test Example 2 as ionic SHCL, the friction reduction effect on the lens surface was evaluated by the following method.

  First, each test solution shown in Table 6 (Comparative Example 10 and Example 6) was prepared. Ionic SHCL (lens I) was immersed in sterile physiological saline for 4 hours (lens pretreatment). Next, after wiping off the physiological saline on the lens surface, each lens was immersed in 10 ml of each test solution and allowed to stand overnight. On the next day, the moisture on the lens surface was lightly wiped, and the logarithmic decay rate was measured every 10 seconds for 3 minutes under conditions of a pendulum weight of 200 g and a sensor diameter of 4 mm under conditions of 25 ° C. and a relative humidity of 60%.

  The result is shown in FIG. As shown in FIG. 6, when the lens I which is ionic SHCL is used, the logarithmic decay rate is significantly reduced by the combination of menthol and tocopherol acetate (Example 6) as compared with the control (Comparative Example 10). Admitted.

  From the above results, it was revealed that friction on the surface of ionic SHCL can be remarkably suppressed by using menthol and tocopherol acetate in combination.

Test Example 6: Evaluation test of bacterial adhesion to SHCL Adhesion of Staphylococcus aureus (ATCC No. 6538) to various soft contact lenses using the test solutions shown in Table 7 (Comparative Examples 11 to 13 and Example 7) Was evaluated. The lens is a lens II (nonionic SHCL, main constituent monomer: N, N-dimethylacrylamide, pyrrolidone compound, silicon-containing methacrylate compound, silicon-containing acrylate compound (USAN: Asmofilcon A), water content 40% as SHCL. BC8.60, DIA14.0) were used.

First, each lens was immersed in 5 mL of sterile physiological saline for 4 hours or more (lens pretreatment). Next, 1 mL of each test solution (Comparative Examples 11 to 13 and Example 7) was placed in a 24-hole multiplate, and moisture on the surface of the lens after pretreatment was sucked with a non-woven fabric, and then one by one. After cut lightly surface moisture of each lens at the edge of the plate after 24 ^{hours, 10 7 ~ 8 CFU / mL} S. aureus bacterial suspension (those that have been suspended in saline) 6 well multi plate containing 5mL of And stored at room temperature for 30 minutes. After 30 minutes, each lens was transferred to a 6-well plate containing 5 mL of physiological saline with tweezers and shaken for 1 minute. Next, each lens is transferred to a Spitz tube containing 5 mL of new physiological saline, subjected to ultrasonic waves (38 kHz) for 3 minutes, and then stirred for 1 minute in a test tube mixer to remove bacteria attached to each lens. The adherent bacteria solution was used.

  The obtained adherent bacterial solution was diluted to an appropriate concentration and seeded on a soy bean / casein / digest / agar medium (SCDLP agar medium). After culturing overnight at 33 ° C., the number of colonies observed was counted, and the number of bacteria attached to each lens (viable cell count) was determined by correcting with the dilution factor.

  The results are shown in FIG. 7 below. As shown in FIG. 7, when treated with a test solution containing each of camphor and tocopherol acetate (Comparative Example 12 and Comparative Example 13), bacterial adhesion to SHCL cannot be suppressed. When treated with a test solution (Example 7) containing camphor and tocopherol acetate, bacterial adhesion to SHCL could be suppressed.

Test Example 7: Evaluation test of bacterial adhesion to SHCL Using the test solutions shown in Table 8 (Comparative Example 14 and Example 8), the adhesion of Staphylococcus aureus (ATCC No. 6538) to various soft contact lenses was evaluated. did. As the lens, the lens II of Test Example 6 was used as SHCL, and the lens F of Reference Test Example 1 was used as a non-silicone hydrogel lens (non-SHCL).

  The test was performed in the same manner as in Test Example 6 above.

  The results are shown in FIG. 8 below. As shown in FIG. 8, it was recognized that SHCL significantly adheres S. aureus to the non-silicone hydrogel lens (Comparative Example 14). And when it processed with the test liquid (Example 8) containing combining three components of menthol, tocopherol acetate, and aminoethylsulfonic acid, it was recognized that the bacterial adhesion to this SHCL can be suppressed. On the other hand, when a non-silicone hydrogel lens was used, no bacterial adhesion inhibitory effect was observed even when the above three components were used in combination.

  From the above results, it was revealed that bacterial adhesion to SHCL can be remarkably suppressed by using a combination of three components, menthol, tocopherol acetate, and aminoethylsulfonic acid. Furthermore, it became clear that this inhibitory effect is specific to SHCL.

Formulation Example In the formulation described in Table 9, eye drops for SHCL (Examples 9-15), SHCL mounting solution (Example 16), SHCL mounting solution and eye drops (Example 17), eyewash for SHCL (Examples) 18) and an SHCL cleaning solution (Example 19) are prepared.

Claims (5)

  An ophthalmic composition for a silicone hydrogel contact lens, comprising (A) a terpenoid and (B) vitamin E. The ophthalmic composition for a silicone hydrogel contact lens according to claim 1, comprising at least one selected from the group consisting of menthol and camphor as component (A). The ophthalmic composition for silicone hydrogel contact lenses according to claim 1 or 2, comprising tocopherol acetate as component (B). The ophthalmic composition for a silicone hydrogel contact lens according to any one of claims 1 to 3, further comprising (C) at least one selected from the group consisting of neostigmine, aminoethylsulfonic acid, and salts thereof. .   The ophthalmic composition for silicone hydrogel contact lens according to any one of claims 1 to 4, which is an eye drop.

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