JP2018197271A - Ophthalmic composition for silicone hydrogel contact lens - Google Patents

Abstract

To provide an ophthalmic composition for silicone hydrogel contact lenses, capable of: inhibiting the accumulation of pollen proteins to ionic SHCLs; or inhibiting the adhesion of corneal cells to nonionic SHCLs.SOLUTION: An ophthalmic composition for silicone hydrogel contact lenses is prepared by using (A) vitamin Bgroups, in combination with (B) at least one selected from the group consisting of chlorpheniramine, glycyrrhizinic acids, and salts thereof.SELECTED DRAWING: None

Description

  The present invention relates to an ophthalmic composition for silicone hydrogel contact lenses. More specifically, the present invention can suppress the accumulation of pollen protein on the ionic silicone hydrogel contact lens, and can suppress the adhesion of corneal cells to the surface of the nonionic silicone hydrogel contact lens. The present invention relates to an ophthalmic composition for a silicone hydrogel contact lens. The present invention also relates to a method for suppressing pollen protein accumulation on an ionic silicone hydrogel contact lens and a method for suppressing adhesion of corneal cells to a nonionic silicone hydrogel contact lens.

  In recent years, the number of wearers of contact lenses has increased, and among them, the number of wearers of soft contact lenses 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 adding silicone to the 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.

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

  Moreover, hay fever is an allergic symptom caused by pollen protein contained in pollen becoming an antigen and contacting mucous membranes. In recent years, the number of patients with hay fever is increasing, which is becoming a major social problem. In the field of ophthalmology, there is a strong demand for the development of ophthalmic compositions useful for preventing hay fever and suppressing deterioration.

On the other hand, vitamin B ₁₂ has been used in ophthalmic compositions for the purpose of imparting an effect of improving the focus adjustment function of the pupil (see Patent Document 1). Further, chlorpheniramine, glycyrrhizic acid, and salts thereof are also known for antihistaminic action, anti-inflammatory action, and the like, and are used in ophthalmic compositions. However, until now, it has not been clarified at all what effect these components have on the silicone hydrogel contact lens. Moreover, the present situation is that it is not even possible to infer the influence of a combination of these specific components on the silicone hydrogel contact lens.

JP 2003-128553 A

  The present inventors have conducted various studies on the adsorption characteristics of pollen proteins to various soft contact lenses (hereinafter, sometimes referred to as SCL), and the ionic silicone hydrogel contact lenses are remarkably adsorbed with pollen proteins. I got a completely new knowledge that it was easy to do. In general, proteins are considered to be difficult to adsorb on silicone hydrogel contact lenses (hereinafter sometimes referred to as SHCL), and this finding is completely unexpected. And generally, when wearing contact lenses, the eyes are likely to dry, and as a result, the cleaning action by tears is reduced, and foreign substances such as pollen are likely to stay in the eyes, which increases the risk of developing hay fever. It is considered. In addition, if a large amount of pollen protein is adsorbed and accumulated on the contact lens, the risk of developing hay fever is significantly increased. Thus, the accumulation of pollen protein in contact lenses can contribute to allergic symptoms. Furthermore, if the pollen protein adsorbed on the contact lens is insufficiently removed, the wearing feeling of the contact lens is impaired, causing discomfort and shortening the use period. Therefore, development of means capable of suppressing the accumulation of pollen proteins in ionic silicone hydrogel contact lenses (hereinafter sometimes referred to as ionic SHCL) is required.

  Furthermore, the present inventors have conducted various studies on the adhesion of corneal epithelial cells of various soft contact lenses, and have not anticipated at all that non-ionic silicone hydrogel contact lenses (hereinafter referred to as non-ionic silicone hydrogel contact lenses). The lens surface (sometimes referred to as ionic SHCL) has obtained a completely new finding that the adhesion of corneal epithelial cells is extremely high. Such a contact lens with high adhesion of corneal epithelial cells is obtained from the eye tissue when the contact lens is worn, when the corneal cell adheres to the lens on the cornea and the lens moves or when the lens is removed. The cells may be peeled off, resulting in damage to the corneal surface and pain associated therewith, and as a result, the quality of life (QOL) of the contact lens user is significantly reduced. Furthermore, considering that silicone hydrogel contact lenses are often worn continuously over a relatively long period of time compared to other soft contact lenses, the nonionic nature of corneal epithelial cells produced by prolonged wear Adhesion to SHCL can also contribute to serious eye disease or ocular mucosal symptoms. Therefore, development of means capable of suppressing adhesion of corneal epithelial cells to nonionic SHCL is also required.

  Thus, one of the objects of the present invention is to promote the removal of pollen protein from ionic SHCL and prevent reattachment, thereby suppressing the accumulation of pollen protein in ionic SHCL. Is to provide. Another object of the present invention is to provide an ophthalmic composition for SHCL that can suppress the adhesion of corneal cells to the surface of nonionic SHCL.

As a result of diligent studies to solve the above-mentioned problems, the present inventors have surprisingly found that (A) vitamin B ₁₂ and (B) chlorpheniramine, glycyrrhizic acid, and salts thereof. It was found that the accumulation of pollen protein in ionic SHCL can be remarkably suppressed when used in combination with at least one more selected. The present inventors have also found that the combined use of the above components (A) and (B) can remarkably suppress the adhesion of corneal epithelial cells to nonionic SHCL. 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) vitamin B ₁₂ and at least one selected from the group consisting of (B) chlorpheniramine, glycyrrhizic acid, and salts thereof.
Item 1-2. Item 1. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-1, which contains cyanocobalamin as the component (A).
Item 1-3. Item 1. The ophthalmic composition for a silicone hydrogel contact lens according to Item 1-1 or 1-2, which contains the component (A) in a total amount of 0.001 to 0.1 w / v%.
Item 1-4. Item (B) The silicone hydrogel contact lens according to any one of Items 1-1 to 1-3, wherein the component includes at least one selected from the group consisting of chlorpheniramine maleate and dipotassium glycyrrhizinate. Ophthalmic composition.
Item 1-5. Item 5. The ophthalmic composition for a silicone hydrogel contact lens according to any one of Items 1-1 to 1-4, wherein the total amount of the component (B) is 0.003 to 1.25 w / v%.
Item 1-6. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-5, further comprising a buffer.
Item 1-7. Item 7. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-6, which contains a borate buffer as a buffer.
Item 1-8. Item 8. The ophthalmic composition for a silicone hydrogel contact lens according to Item 1-6 or 1-7, comprising a buffering agent in a total amount of 0.01 to 10 w / v%.
Item 1-9. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-8, which is an eye drop.
Item 1-10. Item 10. The ophthalmic composition for a silicone hydrogel contact lens according to any one of Items 1-1 to 1-9, which is for an ionic silicone hydrogel contact lens.
Item 1-11. Item 10. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-9, which is for nonionic silicone hydrogel contact lenses.

Moreover, this invention provides the method of suppressing accumulation | storage of pollen protein to ionic SHCL hung up below.
Item 2. An ophthalmic composition for a silicone hydrogel contact lens comprising (A) vitamin B ₁₂ and (B) at least one selected from the group consisting of chlorpheniramine, glycyrrhizic acid, and salts thereof, A method for suppressing the accumulation of pollen protein in an ionic silicone hydrogel contact lens, comprising contacting the silicone hydrogel contact lens.

Moreover, this invention provides the method of providing the effect | action which suppresses accumulation | storage of pollen protein to ionic SHCL hung up below.
Item 3. The ophthalmic composition for silicone hydrogel contact lenses is formulated with (A) vitamin B ₁₂ and at least one selected from the group consisting of (B) chlorpheniramine, glycyrrhizic acid, and salts thereof. A method for imparting to the ophthalmic composition an action that suppresses the accumulation of pollen proteins in an ionic silicone hydrogel contact lens.

The present invention also provides a method for suppressing adhesion of corneal epithelial cells to nonionic SHCL described below.
Item 4. A non-ionic ophthalmic composition for a silicone hydrogel contact lens comprising (A) vitamin B ₁₂ and (B) at least one selected from the group consisting of chlorpheniramine, glycyrrhizic acid, and salts thereof A method for suppressing adhesion of corneal epithelial cells to a nonionic silicone hydrogel contact lens, which comprises contacting with an ionic silicone hydrogel contact lens.

Moreover, this invention provides the method of providing the adhesion | attachment inhibitory action of the corneal epithelial cell with respect to nonionic SHCL to the ophthalmic composition for SHCL shown below.
Item 5. The ophthalmic composition for silicone hydrogel contact lenses is formulated with (A) vitamin B ₁₂ and (B) at least one selected from the group consisting of chlorpheniramine, glycyrrhizic acid, and salts thereof. A method for imparting an adhesion suppressing action of corneal epithelial cells to a nonionic silicone hydrogel contact lens to an ophthalmic composition for a silicone hydrogel contact lens.

  According to the ophthalmic composition for SHCL of the present invention, even when pollen protein and ionic SHCL come into contact with each other during wearing of ionic SHCL, it promotes removal of pollen protein from ionic SHCL and prevents reattachment. Thus, the accumulation of pollen protein in ionic SHCL can be suppressed. Therefore, the risk of developing allergic symptoms can be reduced for users of hay fever or pollinosis reserves. Furthermore, according to the ophthalmic composition for SHCL of the present invention, the ionic SHCL can be kept clean during or before wearing the ionic SHCL.

  In addition, according to the ophthalmic composition for SHCL of the present invention, it is possible to effectively suppress adhesion of corneal epithelial cells to nonionic SHCL. Can improve pain. In addition, it is known that the cornea is difficult to detect even when a soft contact lens is worn, so if you wear nonionic SHCL for a long period of time, it may be left until it becomes severe. . On the other hand, according to the ophthalmic composition for SHCL of the present invention, such adverse effects can be improved, and nonionic SHCL can be continuously worn for a long period of time with high safety.

  As described above, the ophthalmic composition for SHCL of the present invention can solve the problems concerned at the time of wearing ionic and non-ionic SHCL at once, so that high safety and comfort are ensured in the use of SHCL. Can do.

In the reference test example 1, it is a figure which shows the result of having evaluated the adsorptivity of the pollen protein to various soft contact lenses. In Test Example 1, it is a figure which shows the result of having evaluated the effect which the test liquid (Example 1-2 and Comparative Example 1-3) removes the pollen protein adsorbed to ionic SHCL. In the reference test example 2, it is a figure which shows the result of having evaluated the adhesiveness of the corneal epithelial cell of various soft contact lenses.

1. The ophthalmic composition for SHCL The ophthalmic composition for SHCL of the present invention contains vitamin B ₁₂ (hereinafter also referred to as component (A)).

Vitamin B ₁₂ is a known compound having an effect of improving the focus control function of the eye, and may be synthesized by a known method or obtained as a commercial product.

The vitamin B ₁₂ class is not particularly limited as long as it is pharmacologically or physiologically acceptable, and specific examples thereof include cyanocobalamin, its analogs, and salts thereof.

  The analog of cyanocobalamin is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, a ligand on cobalt in cyanocobalamin is substituted. And a compound obtained by substituting a functional group in cyanocobalamin. More specifically, analogs of cyanocobalamin include mecobalamin (methylcobalamin), hydroxocobalamin, adenosylcobalamin, aquacobalamin and the like. One of these analogs of cyanocobalamin may be selected and used alone, or two or more thereof may be used in any combination.

  The salt of cyanocobalamin and its analogs is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Carboxylate (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylate (fumarate, maleate, succinate, malonate, etc.), oxy Carboxylate (lactate, tartrate, citrate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, tosylate, etc.)], inorganic acid salt (eg, hydrochloride, sulfate, Nitrates, hydrobromides, phosphates, etc.) and salts with organic bases (eg methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.) Salts with amines), 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.] . Among these salts, organic acid salts and inorganic acid salts are preferable, and acetates and hydrochlorides are more preferable. One of these salts may be selected and used alone, or two or more of these salts may be used in any combination.

  In the ophthalmic composition for SHCL of the present invention, as the component (A), one of cyanocobalamin, its analogs, and salts thereof may be used alone, or two or more thereof may be arbitrarily selected. May be used in combination. Component (A) used in the present invention from the viewpoint of further improving the action of suppressing the accumulation of pollen protein to ionic SHCL, and from the viewpoint of effectively suppressing adhesion of corneal epithelial cells to nonionic SHCL Preferred examples include cyanocobalamin, mecobalamin, hydroxocobalamin, and salts thereof, more preferably cyanocobalamin and salts thereof, and particularly preferably cyanocobalamin.

  In the ophthalmic composition for SHCL of the present invention, the blending ratio of the component (A) is appropriately set according to the type of the component (A), the formulation form of the ophthalmic composition for SHCL, etc. The total amount of the component (A) is 0.001 to 0.1 w / v%, preferably 0.004 to 0.05 w / v%, more preferably 0.006 to 0.03 w / v% with respect to the total amount of the ophthalmic composition.

  The ophthalmic composition for SHCL of the present invention has at least one selected from the group consisting of chlorpheniramine, glycyrrhizic acid, and salts thereof in addition to the above component (A) (hereinafter referred to as component (B). In some cases). By using the (B) component together with the (A) component in this way, it becomes possible to exert an effect of suppressing the accumulation of pollen protein to ionic SHCL, and adhesion of corneal epithelial cells to nonionic SHCL Can be effectively suppressed.

  Among the components (B), chlorpheniramine is a known compound also called 3- (4-chlorophenyl) -N, N-dimethyl-3-pyridin-2-yl-propylamine.

  The salt of chlorpheniramine is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable. Specific examples thereof include maleate and fumarate. Organic acid salts; inorganic acid salts such as hydrochlorides and sulfates; and various salts such as metal salts. Among these salts, an organic acid salt is preferable, and a maleic acid salt (chlorpheniramine maleate) is more preferable. These chlorpheniramine salts may be used alone or in any combination of two or more.

  Further, chlorpheniramine and a salt thereof may be in the form of a hydrate, and may be any of d-form, l-form, and dl-form.

  Among chlorpheniramine and its salts, chlorphenylamine is preferable from the viewpoint of further enhancing the inhibitory action of pollen protein accumulation on ionic SHCL, and from the viewpoint of effectively suppressing adhesion of corneal epithelial cells to nonionic SHCL. A salt of pheniramine, more preferably chlorpheniramine maleate.

  Among the components (B), glycyrrhizic acid is 20β-carboxy-11-oxo-30-noroleana-12-en-3β-yl-2-O-β-D-glucopyranuronosyl-α-D-glucopyranoside It is a known compound also called uronic acid. Glycyrrhizic acid and salts thereof are known compounds as anti-inflammatory agents or antiallergic agents, and may be synthesized by a known method or obtained as a commercial product.

  The salt of glycyrrhizic acid is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of such salts include salts with organic bases (for example, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, and picoline), inorganic bases, and the like. [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. Among these salts, preferred are salts with inorganic bases, more preferred are salts with alkali metals such as sodium and potassium; ammonium salts and the like. More specifically, examples include salts with alkali metals such as disodium glycyrrhizinate, trisodium glycyrrhizinate, dipotassium glycyrrhizinate, and tripotassium glycyrrhizinate; ammonium salts such as monoammonium glycyrrhizinate. Among these, Preferably the alkali metal salt of glycyrrhizic acid, More preferably, dipotassium glycyrrhizinate is mentioned. These glycyrrhizic acid salts may be used alone or in any combination of two or more.

  In addition, in this invention, when using glycyrrhizic acid and / or its salt as (B) component, the crude drug (for example, licorice) containing glycyrrhizic acid and / or its salt can also be used.

  Among glycyrrhizic acid and its salts, glycyrrhizic acid is preferable from the viewpoint of further enhancing the action of suppressing the accumulation of pollen proteins to ionic SHCL and effectively suppressing the adhesion of corneal epithelial cells to nonionic SHCL. More preferably, an alkali metal salt of glycyrrhizic acid, particularly preferably dipotassium glycyrrhizinate.

  In the ophthalmic composition for ionic SHCL of the present invention, as the component (B), one kind of chlorpheniramine, glycyrrhizic acid, and salts thereof may be used alone, or two or more kinds thereof may be used. Any combination of these may be used. Preferable examples of the component (B) used in the present invention include chlorpheniramine maleate and dipotassium glycyrrhizinate.

  Among the components (B) used in the present invention, glycyrrhizic acid and salts thereof are preferable from the viewpoint of further enhancing the inhibitory action of pollen protein accumulation on ionic SHCL; more preferably, dipotassium glycyrrhizinate is exemplified. Is done. Further, from the viewpoint of further enhancing the adhesion inhibitory action of corneal epithelial cells to nonionic SHCL, preferably chlorpheniramine and its salt; more preferably, chlorpheniramine maleate is exemplified.

In the ophthalmic composition for SHCL of the present invention, the blending ratio of the component (B) is appropriately set according to the type of the component (B), the type of the component (A) to be used together, the formulation form of the ophthalmic composition for SHCL, etc. However, as an example, the total amount of component (B) is 0.003 to 1.25 w / v%, preferably 0.006 to 0.3 w / v%, based on the total amount of the ophthalmic composition for SHCL. More specifically, the following ranges are exemplified as the blending ratio of each component (B) with respect to the total amount of the ophthalmic composition for SHCL.
When component (B) is chlorpheniramine and / or a salt thereof: These are generally in a total amount of 0.003 to 0.15 w / v%, preferably 0.005 to 0.1 w / v%, more preferably 0.006 to 0.05 w / v%. ;
When the component (B) is glycyrrhizic acid and / or a salt thereof: These are total amounts, usually 0.005-1.25 w / v%, preferably 0.01-1.0 w / v%, more preferably 0.05-0.3 w / v%.

In addition, 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 further enhances the action of suppressing the accumulation of pollen proteins in ionic SHCL. Alternatively, from the viewpoint of further enhancing the inhibitory effect of corneal epithelial cell adhesion to nonionic SHCL, the total amount of component (B) is 15 to 21,000 parts by weight, preferably 30 to 100 parts by weight per 100 parts by weight of component (A). A range of 4500 parts by weight is exemplified. More specifically, examples of the ratio of the component (B) per 100 parts by weight of the total amount of the component (A) include the following ranges:
When component (B) is chlorpheniramine and / or a salt thereof: usually 15 to 2500 parts by weight, preferably 25 to 850 parts by weight, more preferably 30 to 500 parts by weight;
When the component (B) is glycyrrhizic acid and / or a salt thereof: These are total amounts, usually 25 to 21000 parts by weight, preferably 50 to 5000 parts by weight, more preferably 250 to 4500 parts by weight.

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 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) and 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, nonionic surfactants are preferably used; more preferably, POE sorbitan fatty acid esters, POE hydrogenated castor oil, or POE / POP block copolymers are 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 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.
Antihistamines: for example, iproheptin, diphenhydramine hydrochloride, ketotifen fumarate, pemirolast potassium and the like.
Decongestant: For example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline sulfate, epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, and the like.
Fungicide: For example, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, polyhexamethylene biguanide hydrochloride, and the like.
Vitamins: for example, flavin adenine dinucleotide sodium, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate and the like tocopherol acetate.
Amino acids: For example, potassium aspartate, magnesium aspartate, aminoethylsulfonic acid and the like.
Anti-inflammatory agent: for example, pranoprofen, allantoin, azulene, sodium azulenesulfonate, guaiazulene, ε-aminocaproic acid, berberine chloride, berberine sulfate, lysozyme chloride, licorice and the like.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Other: For example, sodium cromoglycate, sodium chondroitin sulfate, sulfamethoxazole, sulfamethoxazole sodium and the like.

In addition, in the ophthalmic composition for 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. May be used in an appropriate amount. As such additives, for example, Pharmaceutical Additives Encyclopedia 2007
Examples include various additives described in (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Carrier: An aqueous carrier such as water or hydrous ethanol.
Thickeners: for example, carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, alginic acid, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol and the like.
Sugars: For example, cyclodextrins and the like. Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.
Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, etc.), Glow Kill (product of Rhodia) Name) etc.
pH adjuster: for example, hydrochloric acid, boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, boro Sand, triethanolamine, monoethanolamine, diisopropanolamine, sulfuric acid, phosphoric acid, polyphosphoric acid, propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, gluconolactone, ammonium acetate etc.
Stabilizers: for example, dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate and the like.
Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), and the like.
Perfume or refreshing agent: for example, menthol, anethole, eugenol, camphor, geraniol, cineol, borneol, limonene, ryuno and the like. These may be either d-form, l-form or dl-form, and are formulated as essential oils (mint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil, etc.) May be.

  The ophthalmic composition for 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 can be easily used while wearing ionic SHCL, and can effectively suppress the accumulation of pollen protein during wearing ionic SHCL, so that discomfort during wearing ionic SHCL It is preferable in that it is possible to wear ionic SHCL comfortably. SHCL eye drops or SHCL eye drops, especially SHCL eye drops, when the non-ionic SHCL is in contact with the eyeball surface or immediately before contact (for example, within 10 minutes before the wearing action to be contacted) ) And is a pharmaceutical form that strongly requires an inhibitory effect on adhesion of corneal epithelial cells to nonionic SHCL. And since an eye drop generally has high use frequency per day compared with other ophthalmic compositions, the effect of this invention can be show | played much more effectively. Considering these viewpoints comprehensively, 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. According to the ophthalmic composition for SHCL of the present invention, when ionic SHCL is to be applied, accumulation of pollen protein in ionic SHCL can be suppressed, and nonionic SHCL is to be applied. In some cases, adhesion of corneal epithelial cells to nonionic SHCL can be suppressed. In addition, ionicity here means that the content of ionic components in the material is 1 mol% or more in accordance with US FDA (US Food and Drug Administration) standards, as normally understood by those skilled in the art. The property means that the content of ionic components in the material is less than 1 mol% in accordance with US FDA standards.

  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. In particular, nonionic SHCL having a moisture content of 35% or less tends to have particularly strong adhesion to corneal epithelial cells. According to the ophthalmic composition for SHCL of the present invention, the effect of suppressing adhesion of corneal epithelial cells can be effectively exhibited even for nonionic SHCL having strong adhesion to corneal epithelial cells. In view of the effects of the present invention, a suitable application target of the ophthalmic composition for SHCL of the present invention is nonionic SHCL having a moisture content of 35% or less.

  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.

  Also, compared to non-silicone hydrogel contact lenses, which are generally softer, silicone hydrogel contact lenses, which are harder, are more susceptible to deterioration of the feeling of use due to lens deformation and reduced wettability due to the adsorption of foreign substances. It is easy to cause. According to the ophthalmic composition for SHCL of the present invention, it is possible to effectively suppress the accumulation of pollen protein in the ionic SHCL of a hard material that easily causes deterioration of the feeling of use and ocular mucosal damage. By preventing deformation and alteration, it is possible to effectively prevent deterioration of the feeling of use and ocular mucosal damage. In view of the effects of the present invention, a suitable application target of the ophthalmic composition for ionic SHCL of the present invention is ionic SHCL having a relatively high hardness. Preferably, the hardness of the ionic SHCL to be applied is 3 g or more, preferably 4 g or more, more preferably 6 g or more, still more preferably 8 g or more when measured by the following measurement method using a texture analyzer. . The upper limit of the hardness of the ionic 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 may be used for improving the focus adjustment function of the eye, or may be used for applications such as anti-allergy and anti-inflammatory.

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

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

  In addition, the ophthalmic composition for SHCL of the present invention can promote the removal of pollen protein from ionic SHCL and prevent re-adhesion, and thus can effectively suppress the accumulation of pollen protein in ionic SHCL. Therefore, the pollen protein adsorbed on the contact lens is prevented from being kept in contact with the eye for a long time, and it is also effective in preventing allergy and preventing deterioration due to pollen. Therefore, it is suitable for application to ionic SHCL users of hay fever or hay fever reserve.

2. A method for suppressing the accumulation of pollen protein in ionic SHCL, and a method for imparting an inhibitory action on the accumulation of pollen protein in ionic SHCL. Also, as described above, the above components (A) and (B) are used in combination. Can promote pollen protein removal from ionic SHCL and prevent reattachment even when ionic SHCL wearing eyes are exposed to pollen, thus suppressing pollen protein accumulation in ionic SHCL become. Accordingly, the present invention, from yet another point of view, is an SHCL containing (A) vitamin B ₁₂ and at least one selected from the group consisting of (B) chlorpheniramine, glycyrrhizic acid, and salts thereof. An ophthalmic composition is brought into contact with ionic SHCL, and a method for suppressing pollen protein accumulation in ionic SHCL is provided. Furthermore, the ophthalmic composition for SHCL is formulated with (A) vitamin B ₁₂ and at least one selected from the group consisting of (B) chlorpheniramine, glycyrrhizic acid, and salts thereof. And a method for imparting to the ophthalmic composition an action of suppressing pollen protein accumulation in ionic SHCL.

  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”.

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

Accordingly, the present invention, from yet another point of view, is an SHCL containing (A) vitamin B ₁₂ and at least one selected from the group consisting of (B) chlorpheniramine, glycyrrhizic acid, and salts thereof. Provided is a method for suppressing adhesion of corneal epithelial cells to nonionic SHCL, wherein the ophthalmic composition is brought into contact with nonionic SHCL. Furthermore, the ophthalmic composition for SHCL is characterized by blending (A) vitamin B ₁₂ and (B) at least one selected from the group consisting of chlorpheniramine, glycyrrhizic acid, and salts thereof. And providing a method for imparting an adhesion inhibitory action of corneal epithelial cells to nonionic SHCL to an ophthalmic composition for SHCL.

  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”.

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

Reference Test Example 1: Evaluation of Pollen Protein Adsorption Characteristics to SCL Four kinds of soft contact lenses shown in Table 1 were used for the test to evaluate the pollen protein adsorption characteristics to the soft contact lenses.

  First, the lenses used for the test were immersed one by one in 4 mL of physiological saline and stored overnight at room temperature (lens pretreatment).

Pollen protein antigen (Cedar Pollen Extract-Ja, manufactured by LSL , Inc., property: freeze-dried powder (Cedar Pollen crude extract Mountain ceder , extracted from pollen of Juniperus Asheii )) dissolved in physiological saline 5 mg / 30 mL pollen protein solution was prepared. In each hole of the 24-well plate, 1.0 mL of pollen protein solution was put, and after wiping off excess moisture from the pretreated lens, it was immersed and shaken at 34 ° C. and 120 rpm for 18 hours. Next, take out the lens, quickly soak (about 1 second) in 100 mL of physiological saline, rinse the excess liquid, and then lightly drain the water using the edge of a beaker, then put the pollen protein into each hole of the 24-well plate. It was immersed in 1 mL of separation liquid (aqueous solution containing 1% sodium carbonate and 1% SDS). The mixture was shaken at 34 ° C. and 120 rpm for 3 hours to separate the pollen protein adsorbed on the lens into the pollen protein separation solution.

  Using a micro BCA assay kit (Thermo SCIENTIFIC, Pierce # 23235), the amount of pollen protein in the pollen protein separation solution was quantified as an albumin equivalent value to determine the amount of pollen protein adsorbed to the lens.

  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.

  The results are shown in FIG. When the lens 1 that is ionic SHCL is used, the adsorption of pollen protein is significantly higher than the lenses 3 and 4 that are non-silicon lenses and the lens 2 that is a non-ionic silicone hydrogel contact lens. Was recognized. From this result, pollen protein tends to adsorb very large amount to ionic SHCL among soft contact lenses, and ionic SHCL has a unique problem that it is very easy to adsorb pollen protein. Was confirmed.

Test Example 1: Evaluation of suppression of pollen protein accumulation against ionic SHCL (1)
The following test was carried out using the lens 1 (ionic SHCL) in which significant adsorption of pollen protein was confirmed in Reference Test Example 1 above.

  First, the lenses 1 were immersed one by one in 5 mL of physiological saline and stored at room temperature for 5 hours (lens pretreatment). Pollen protein antigen (CEL Pollen Extract-Ja, manufactured by LSL Co., Ltd.) Properties: Lyophilized powder (Cedar Pollen crude extract Mountain ceder, extracted from pollen of Juniperus Asheii) in physiological saline, A 5 mg / 50 mL pollen protein solution was prepared. 1.0 mL of the pollen protein solution was put into each hole of the 24-well plate, the excess moisture of the pretreated lens was wiped off and immersed, and shaken at 34 ° C. and 400 rpm for 24 hours.

  Take out the lens 1 soaked in the pollen protein solution, quickly soak it in 100 mL of physiological saline (about 1 second), rinse the excess solution, wipe off the water, and put it in a 24-well plate. Each was immersed in 1.0 mL of a prescription solution (Example 1-2, Comparative Example 1-3 and control) and shaken at 34 ° C. and 400 rpm for 18 hours. After that, take out the lens 1, soak it quickly (about 1 second) in 100 mL of physiological saline, rinse the excess liquid, and then use a beaker's edge to lightly drain the water and place it in a 24-well plate. It was immersed in 0.5 mL of the liquid for use (aqueous solution containing 1% sodium carbonate and 1% SDS). The mixture was shaken at 34 ° C. and 400 rpm for 3 hours to separate the pollen protein adsorbed on the lens into the pollen protein separation solution.

  Moreover, in order to calculate the amount of pollen protein adsorption more accurately by subtracting the influence of each prescription solution, as a blank group, except that the step of treating with the pollen protein solution was changed to treatment with physiological saline, In the same manner as described above, a treatment with each prescription solution and a treatment with a pollen protein separation solution was prepared.

  Using a micro BCA assay kit (Thermo SCIENTIFIC, Pierce # 23235), the amount of pollen protein present in the pollen protein separation solution was quantified as an albumin equivalent, and the amount of pollen protein detached from lens 1 (pollen) Protein adsorption amount) was determined. In calculating the amount of pollen protein adsorbed, the amount of pollen protein adsorbed was determined by subtracting the absorbance of the blank group from the absorbance of each sample and calculating it as an albumin equivalent value. Then, according to the following formula, the pollen protein adsorption improvement rate (%) is calculated from the ratio of the amount of pollen protein adsorbed when the test solution of the comparative example and the example is used relative to the amount of pollen protein adsorbed when the control test solution is used. Calculated.

  The results are shown in FIG. As a result, when any of cyanocobalamin, chlorpheniramine maleate, and dipotassium glycyrrhizinate is used alone (Comparative Example 1-3), the amount of pollen protein adsorbed on ionic SHCL tends to be reduced. Was not recognized at all. On the other hand, unexpectedly, when chlorcophenamine maleate or dipotassium glycyrrhizinate is used in combination with cyanocobalamin (Example 1-2), the improvement rate of pollen protein adsorption is remarkably enhanced. It was revealed that the amount of pollen protein adsorbed on ionic SHCL can be greatly reduced and accumulation can be suppressed (Example 1-2).

Reference Test Example 2: Evaluation of Adhesion of Corneal Epithelial Cells of Various SCLs The following experiment was conducted using five types of soft contact lenses shown in Table 3, and the adhesion of corneal epithelial cells on the soft contact lens surface was evaluated. The soft contact lenses used in this test are all commercially available products.

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

  The obtained results are shown in FIG. As is clear from FIG. 3, the lenses A and B, which are nonionic SHCL, are significantly more corneal epithelial cells than the lenses C, which are ionic SHCL, and lenses D or E, which are non-silicone hydrogel contact lenses. It was confirmed that there was adhesiveness. In addition, when the adhesion state of the cells to the soft contact lens was observed with a microscope, cell adhesion was hardly confirmed in the lenses C, D, and E, but corneal epithelial cells were present on the entire surfaces of the lenses A and B. It was confirmed that they were adhered. From the above results, it was confirmed that nonionic SHCL has significantly higher adhesion of corneal epithelial cells than other types of lenses, and wearing nonionic SHCL has adverse effects such as damage to the corneal surface. It became clear that it could be given.

Test example 2: Adhesion inhibition test of corneal epithelial cells to nonionic SHCL:
Using the test solution shown in Table 4, the adhesion inhibitory effect of corneal epithelial cells on nonionic SHCL was evaluated.

Lens B (nonionic SHCL) shown in Table 3 was immersed one by one in 3 mL of the test solution (Example 3) shown in Table 4 and allowed to stand at 34 ° C. for 24 hours. Lens B taken out from each test solution is gently washed with physiological saline, then wiped off, and the convex surface is placed on a 24-well plate containing 900 μL of growth medium (DMEM medium containing 10% fetal bovine serum). One piece was immersed. Each well was seeded with 100 μL each of a cell suspension (1 × 10 ⁵ cell / mL) of a rabbit corneal epithelial cell line SIRC (ATCC number: CCL-60) prepared using a growth medium, and incubated at 37 ° C., 5 ° C. After culturing for 48 hours under% CO ₂ conditions, the number of viable cells adhered to the lens was counted (sample group). As a control, instead of each test solution, using lens B immersed in the control test solution shown in Table 4, a cell suspension of a rabbit corneal epithelial cell line was seeded and cultured under the same conditions as above. The number of viable cells adhered to the lens B was counted (control group). Furthermore, as a blank, a well was prepared by adding only 1000 μL of a growth medium (DMEM medium containing 10% fetal bovine serum) without seeding rabbit corneal epithelial cells. The mixture was allowed to stand for 48 hours under the conditions of 5 ° C. and 5% CO ₂ (blank group). In addition, the cell adhesion suppression rate (%) was computed according to the following formula using Cell Counting Kit (made by Dojindo Laboratories) for the measurement of the number of living cells.

  The obtained results are also shown in Table 4. As shown in Table 4, it was revealed that a markedly higher cell adhesion inhibitory effect was exhibited with respect to nonionic SHCL by using a combination of cyanocobalamin and chlorpheniramine maleate.

Formulation Example An ophthalmic solution for SHCL (Example 4-10), an SHCL mounting solution (Example 11), an SHCL mounting solution and an eye drop (Example 12), an SHCL eyewash (Example) 13) and an SHCL cleaning solution (Example 14) are prepared.

Claims (1)

An ophthalmic composition for a silicone hydrogel contact lens, comprising (A) vitamin B ₁₂ and at least one selected from the group consisting of (B) chlorpheniramine, glycyrrhizic acid, and salts thereof.

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