JP2013006877A - Eye drop for ionic silicone hydrogel contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an eye drop for ionic silicone hydrogel contact lenses (SHCL), containing chlorpheniramine and/or its salts and inhibited with the adsorption of these components to the ionic SHCL.SOLUTION: The eye drop for the ionic silicone hydrogel contact lenses is prepared by using (A) at least 1 kind selected from the group consisting of the chlorpheniramine and its salts, together with (B) a polycarboxylic acid and/or its salts simultaneously.

Description

  The present invention relates to an eye drop for an ionic silicone hydrogel contact lens that can suppress adsorption of chlorpheniramine and / or a salt thereof to the ionic silicone hydrogel contact lens.

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

  Under such circumstances, silicone hydrogel contact lenses have been developed in recent years as soft contact lenses having high oxygen permeability. Silicone hydrogel contact lenses achieve oxygen permeability several times that of conventional hydrogel contact lenses by 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 indispensable to design an eye drop applied to the eye of a contact lens wearer with sufficient 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 eye drops applied to the eyes of soft contact lens wearers depend on the characteristics of the applied soft contact lens. It is important to design the drug product.

  On the other hand, chlorpheniramine and a salt thereof have been incorporated in eye drops so far for the purpose of imparting an antiallergic effect based on histamine H1 receptor antagonism (see Patent Documents 1-3). However, there has been no report on the influence of chlorpheniramine and its salt on ionic silicone hydrogel contact lenses. For this reason, in the eye drops for ionic silicone hydrogel contact lenses, it is currently not clear whether or not chlorpheniramine and its salt are blended properly.

JP 2005-162747 A Japanese Patent Laying-Open No. 2005-330276 JP 2006-39529 A

The inventors of the present invention have studied various effects of chlorpheniramine and / or its salt on various soft contact lenses. As a result, chlorpheniramine and / or a salt thereof is an ionic silicone hydrogel contact lens (hereinafter referred to as “ionic silicone hydrogel contact lens”). , Abbreviated as ionic SHCL). If the composition of the eye drop is adsorbed to the soft contact lens in this way, the soft contact lens may be deformed or the wettability of the lens may be reduced, and the adsorbed component may be affected by remaining on the lens. . In particular, since the material of SHCL is harder than other soft contact lenses, there is a tendency that the feeling of use is likely to be deteriorated due to deformation of the lens or decrease in wettability. Furthermore, considering that SHCL is often worn continuously over a relatively long period of time compared to other soft contact lenses, it can cause serious eye damage if the lens is continuously worn over a long period of time. It can also contribute to disease or ocular mucosal symptoms.

  Therefore, development of means for effectively suppressing adsorption of chlorpheniramine and / or a salt thereof to ionic SHCL is required.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have used chlorpheniramine and / or a salt thereof and a polycarboxylic acid and / or a salt thereof in combination to produce chlorpheniramine for ionic SHCL. And / or the salt adsorption thereof was found to be significantly suppressed. In particular, the effect of suppressing the adsorption of chlorpheniramine and / or its salt to ionic SHCL is, as polycarboxylic acid, chondroitin sulfate, hyaluronic acid, alginic acid, glycyrrhizic acid, aspartic acid, citric acid, and / or salts thereof It has been found that the use of is significantly more pronounced. The present invention has been completed by making further improvements based on such findings.

That is, the present invention provides the following eye drops for ionic SHCL.
Item 1. An ion comprising (A) at least one selected from the group consisting of chlorpheniramine and a salt thereof and (B) at least one selected from the group consisting of a polycarboxylic acid and a salt thereof Eye drops for water-soluble silicone hydrogel contact lenses.
Item 2. Item 4. An eye drop for an ionic silicone hydrogel contact lens according to Item 1, comprising chlorpheniramine maleate as the component (A).
Item 3. Item 3. The ionic silicone according to Item 1 or 2, comprising as component (B) at least one selected from the group consisting of chondroitin sulfate, hyaluronic acid, alginic acid, glycyrrhizic acid, aspartic acid, citric acid, and salts thereof. Eye drops for hydrogel contact lenses.

In addition, the present invention provides a method for suppressing adsorption of chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens, and a chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens. Provided is a method for imparting an eye drop with an action of suppressing the adsorption of water.
Item 4. (A) at least one selected from the group consisting of chlorpheniramine and a salt thereof and (B) at least one selected from the group consisting of a polycarboxylic acid and a salt thereof, A method for suppressing adsorption of chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens.
Item 5. Item 5. The adsorption suppression method according to Item 4, comprising chlorpheniramine maleate as the component (A).
Item 6. Item 6. The adsorption inhibiting method according to Item 4 or 5, comprising as component (B) at least one selected from the group consisting of chondroitin sulfate, hyaluronic acid, alginic acid, glycyrrhizic acid, aspartic acid, citric acid, and salts thereof. .
Item 7. (A) An eye drop for an ionic silicone hydrogel contact lens containing at least one selected from the group consisting of chlorpheniramine and its salt is selected from the group consisting of (B) polycarboxylic acid and its salt At least 1 type is mix | blended, The method to provide the eyedrop with the effect | action which suppresses adsorption | suction of the chlorpheniramine and / or its salt with respect to an ionic silicone hydrogel contact lens characterized by the above-mentioned.

In addition, the present invention provides a method for suppressing deformation of an ionic silicone hydrogel contact lens by chlorpheniramine and / or a salt thereof, and an ionic silicone hydrogel contact lens by chlorpheniramine and / or a salt thereof described below. A method for imparting an eye drop with an action of suppressing deformation of the eye drops is provided.
Item 8. (A) at least one selected from the group consisting of chlorpheniramine and a salt thereof and (B) at least one selected from the group consisting of a polycarboxylic acid and a salt thereof, A method for suppressing deformation of an ionic silicone hydrogel contact lens by chlorpheniramine and / or a salt thereof.
Item 9. Item 9. The deformation suppression method according to Item 8, comprising chlorpheniramine maleate as the component (A).
Item 10. Item 10. The deformation inhibiting method according to Item 8 or 9, comprising as component (B) at least one selected from the group consisting of chondroitin sulfate, hyaluronic acid, alginic acid, glycyrrhizic acid, aspartic acid, citric acid, and salts thereof. .
Item 11. (A) An eye drop for an ionic silicone hydrogel contact lens containing at least one selected from the group consisting of chlorpheniramine and its salt is selected from the group consisting of (B) polycarboxylic acid and its salt At least 1 type is mix | blended, The method to provide the effect | action which suppresses the deformation | transformation of the ionic silicone hydrogel contact lens by the chlorpheniramine and / or its salt to an eye drop.

The present invention also provides the following agent for suppressing adsorption of chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens, and an ionic silicone by chlorpheniramine and / or a salt thereof An agent for suppressing deformation of a hydrogel contact lens is provided.
Item 12. (B) In order to suppress adsorption of (A) chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens containing at least one selected from the group consisting of a polycarboxylic acid and a salt thereof Agent.
Item 13. (B) An agent for suppressing deformation of an ionic silicone hydrogel contact lens caused by chlorpheniramine and / or a salt thereof, containing at least one selected from the group consisting of a polycarboxylic acid and a salt thereof.

Furthermore, the present invention also provides the uses listed below.
Item 14. (A) At least one selected from the group consisting of chlorpheniramine and a salt thereof and (B) at least one selected from the group consisting of a polycarboxylic acid and a salt thereof for eye drops for ionic silicone hydrogel contact lenses Use for the manufacture of agents.
Item 15. Item 15. The use according to Item 14, comprising chlorpheniramine maleate as the component (A).
Item 16. Item 16. The use according to Item 14 or 15, comprising as component (B) at least one selected from the group consisting of chondroitin sulfate, hyaluronic acid, alginic acid, glycyrrhizic acid, aspartic acid, citric acid, and salts thereof.

According to the present invention, it is possible to effectively suppress the adsorption of chlorpheniramine and / or a salt thereof to ionic SHCL, so that chlorpheny can be safely instilled before or before wearing ionic SHCL. An eye drop containing lamin and / or a salt thereof is provided. Chlorpheniramine and / or its salts have anti-allergic action, so it is desirable to be administered to the eyes when allergic symptoms of the eyes occur due to pollen, etc., but until now when wearing SCL (including SHCL) An eye drop containing chlorpheniramine and / or a salt thereof that can be instilled is not commercially available. Therefore, until now, every time an allergic symptom of the eye appears, it is necessary for the SCL wearer to remove the SCL once and apply an eye drop having the above-mentioned antiallergic action. According to the present invention, an eye drop containing chlorpheniramine and / or a salt thereof can be safely instilled with an ionic SHCL wearer wearing a contact lens.

  In addition, it is known that the ocular mucosa is difficult to detect even when a soft contact lens is worn, so it becomes severe if ionic SHCL with a large amount of drug adsorbed and deformed is worn for a long period of time. There is a risk of leaving. On the other hand, according to the ophthalmic solution for ionic SHCL of the present invention, it is possible to suppress adsorption of chlorpheniramine and / or a salt thereof to ionic SHCL, and to suppress deformation of ionic SHCL. It becomes possible to wear ionic SHCL continuously for a long time.

  Furthermore, the adsorption of chlorpheniramine and / or its salt to soft contact lenses can reduce the wettability of the lens. According to the present invention, such adsorption can be effectively suppressed, so that it is possible to prevent a decrease in wettability of the lens.

In the reference test example 1, it is a figure which shows the result of having evaluated the adsorption | suction characteristic (the amount of chlorpheniramine maleate (microgram / CL) adsorb | sucked to a contact lens) of the chlorpheniramine maleate to various soft contact lenses. In Test Example 1, the effect of suppressing the adsorption of chlorpheniramine maleate to the ionic SHCL and ionic non-silicone hydrogel contact lens of the test solution (Example 1) (adsorption inhibition rate of chlorpheniramine maleate (%)) It is a figure which shows the result of having evaluated. In Experiment 2, it is a figure which shows the result of having evaluated the adsorption inhibitory effect (adsorption inhibitory rate (%) of chlorpheniramine maleate) of the chlorpheniramine maleate with respect to ionic SHCL of a test liquid (Example 2-4). is there. In Experiment 3, it is a figure which shows the result of having evaluated the adsorption inhibitory effect (adsorption inhibitory rate (%) of chlorpheniramine maleate) of chlorpheniramine maleate with respect to ionic SHCL of a test liquid (Example 5-9). is there. In Test example 4, it is a figure which shows the result of having evaluated the adsorption inhibitory effect (adsorption inhibitory rate (%) of chlorpheniramine maleate) of the chlorpheniramine maleate with respect to ionic SHCL of a test liquid (Examples 10-17). is there. In Test Example 5, it is a figure which shows the result of having evaluated the lens size deformation | transformation inhibitory effect with respect to ionic SHCL of a test liquid (Example 6). In Experiment 6, it is a figure which shows the result of having evaluated the adsorption inhibitory effect (adsorption inhibitory rate (%) of chlorpheniramine maleate) of the chlorpheniramine maleate with respect to ionic SHCL of a test liquid (Example 18). In Experiment 7, it is a figure which shows the result of having evaluated the adsorption inhibitory effect (adsorption inhibitory rate (%) of chlorpheniramine maleate) of the chlorpheniramine maleate with respect to ionic SHCL of a test liquid (Example 19-21). is there. In Experiment 8, it is a figure which shows the result of having evaluated the adsorption inhibitory effect (adsorption inhibitory rate (%) of chlorpheniramine maleate) of the chlorpheniramine maleate with respect to ionic SHCL of a test liquid (Examples 22-24). is there.

(I) Eye drops for ionic SHCL The eye drops for ionic SHCL of the present invention are at least one selected from the group consisting of chlorpheniramine and a salt thereof (hereinafter sometimes simply referred to as component (A)). ). Chlorpheniramine and salts thereof are known compounds as antihistamines, and may be synthesized by a known method or obtained as a commercial product.

Among the components (A) used in the present invention, the salt of chlorpheniramine is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specifically, organic acid salts such as maleate and fumarate; inorganic acid salts such as hydrochloride and sulfate; and various salts such as metal salts. Among these salts, organic acid salts are preferable, and maleates are 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.

In the eye drop for ionic SHCL of the present invention, as the component (A), one kind of chlorpheniramine and a salt thereof may be selected and used alone, or two or more kinds May be used in any combination. As the component (A), preferably a salt of chlorpheniramine,
More preferred is an organic acid salt of chlorpheniramine, particularly preferably a maleic acid salt of chlorpheniramine (chlorpheniramine maleate).

In the ionic SHCL eyedrops of the present invention, the blending ratio of the component (A) is appropriately set according to the type of the component (A), the types of other blending components, the use of the eyedrops, etc. However, as an example, the total amount of the component (A) is 0.001 w / v% or more with respect to the total amount of the eye drop. From the viewpoint of obtaining an excellent medicinal effect while considering safety for eyes, the total amount of the component (A) is preferably 0.005 w / v% or more, more preferably 0.01 to 0.1 w / Examples are v%, particularly preferably 0.01 to 0.03 w / v%.

Further, the eye drop for ionic SHCL of the present invention is at least one selected from the group consisting of polycarboxylic acids and salts thereof in addition to the above component (A) (hereinafter simply referred to as component (B). Is also included. Thus, it becomes possible to suppress adsorption | suction of the said (A) component with respect to ionic SHCL by using polycarboxylic acid and / or its salt together with said (A) component.

The polycarboxylic acid used as the component (B) is a compound having two or more carboxyl groups, and is limited to being pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. There is no particular limitation. Specific examples of the polycarboxylic acid used as the component (B) include polysaccharide-type polycarboxylic acids such as chondroitin sulfate, hyaluronic acid, alginic acid, and carboxymethyl cellulose; triterpene glycoside-type polycarboxylic acids such as glycyrrhizic acid; Examples include amino acid type dicarboxylic acids such as aspartic acid and glutamic acid; and hydroxy acid type polycarboxylic acids such as citric acid and malic acid.

The salt of the polycarboxylic acid used in the component (B) is particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. However, for example, salts with inorganic bases [eg ammonium salts; alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), salts with metals such as aluminum, etc.], organic bases and Salts (eg, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), inorganic acid salts (eg, hydrochloride, sulfate, nitrate, hydrogen bromide) Acid salts, phosphates, etc.), organic acid salts [for example, monocarboxylates (acetate, trifluoroacetate, butyrate, palmitate, stearin Salt), polyvalent carboxylate (fumarate, maleate, succinate, malonate, etc.), oxycarboxylate (lactate, tartrate, citrate, etc.), organic sulfonate ( Methanesulfonate, toluenesulfonate, tosylate, etc.)] and the like. Among these salts, preferred are salts with inorganic bases, more preferred are alkali metal salts and / or alkaline earth metal salts.

Specifically, in the case of chondroitin sulfate, sodium salt, potassium salt, etc .; in the case of hyaluronic acid, sodium salt, potassium salt, etc .; in the case of alginic acid, sodium salt, potassium salt, etc .; glycyrrhizin In the case of acid, sodium salt, potassium salt, etc .; In the case of aspartic acid, sodium salt, potassium salt, magnesium salt, calcium salt, magnesium salt, potassium salt, etc .; In the case of citric acid, sodium salt And potassium salts.

  The said salt of polycarboxylic acid may be used individually by 1 type, and may be used in combination of 2 or more type.

Among these (B) components, from the viewpoint of making the effect of suppressing the adsorption of the above (A) component to ionic SHCL even more remarkable, preferably, as the above (B) component, chondroitin sulfate, hyaluronic acid , Alginic acid, glycyrrhizic acid, aspartic acid, citric acid, and salts thereof; more preferably sodium chondroitin sulfate, sodium hyaluronate, dipotassium glycyrrhizinate, magnesium potassium aspartate, potassium aspartate, alginic acid, sodium citrate It is.

In the eye drop for ionic SHCL of the present invention, one type may be selected and used alone as the component (B), or two or more types may be used in any combination. In order to obtain a more excellent adsorption suppressing effect, it is preferable to use a combination of two or more types as the component (B).

In the eye drop for ionic SHCL of the present invention, the blending ratio of the component (B) is the type of the component (B), the type and blending ratio of the component (A) and other components, the use of the eye drop, etc. However, 0.0001 to 10 w / v% is typically exemplified. From the viewpoint of making the effect of suppressing the adsorption of the component (A) to the ionic SHCL even more remarkable, the blending ratio of the component (B) is preferably 0.0005 to 5 w / v%, more preferably 0.001 to 3w / v% is exemplified. Further, from the viewpoint of remarkably exerting the effect of suppressing the adsorption of the component (A) to the ionic SHCL, the following ranges are exemplified as the blending ratio for each type of the component (B).
When component (B) is chondroitin sulfate and / or a salt thereof: 0.01 to 2 w / v%, preferably 0.02
-1 w / v%, more preferably 0.05-0.5 w / v%, more preferably 0.3-0.5 w / v%.
When component (B) is hyaluronic acid and / or a salt thereof: 0.0005 to 0.5 w / v%, preferably 0.001 to 0.4 w / v%, more preferably 0.005 to 0.3 w / v%.
When component (B) is alginic acid and / or a salt thereof: 0.0025 to 1.0 w / v%, preferably 0.005 to 0.5 w / v%, more preferably 0.01 to 0.25 w / v%.
When component (B) is glycyrrhizic acid and / or a salt thereof: 0.005 to 1.0 w / v%, preferably 0.01 to 0.5 w / v%, more preferably 0.05 to 0.25 w / v%.
When component (B) is aspartic acid and / or a salt thereof: 0.005 to 5 w / v%, preferably 0.01 to 2.5 w / v%, more preferably 0.05 to 2 w / v%.
When component (B) is citric acid and / or a salt thereof: 0.0001 to 5 w / v%, preferably 0.001 to 2 w / v%, more preferably 0.01 to 1 w / v%.

In the eye drop for ionic SHCL of the present invention, the ratio of the component (B) to the component (A) is not particularly limited as long as the blending ratio described above is satisfied. ) From the viewpoint of making the effect of suppressing the adsorption of the component more remarkable, the total amount of the component (B) is 0.025 to 2000 parts by weight, preferably 0.05 to 1000 parts by weight per 1 part by weight of the total amount of the component (A). Part, more preferably 0.1 to 400 parts by weight.

The eye drops for ionic SHCL of the present invention may further contain a surfactant in addition to the components (A) and (B). Thus, by containing a surfactant, the effect of suppressing the adsorption of the component (A) to ionic SHCL can be more effectively exhibited. The surfactant that can be blended in the eye drops for ionic SHCL of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and a nonionic interface. Any of an active agent, an amphoteric surfactant, an anionic surfactant, and a cationic surfactant may be used.

Specific examples of nonionic surfactants that can be incorporated into the eye drops for ionic SHCL of the present invention include POE (20) sorbitan monolaurate (Polysorbate 20), POE monopalmitate 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); 407, Poloxamer 235, Poloxamer 188, Poloxamer 403, Poloxamer 237
POE / POP block copolymers such as poloxamer 124; POE hydrogenated castor oil such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE alkyl ethers such as POE (9) lauryl ether; POE (20) POE-POP alkyl ethers such as POP (4) cetyl ether; POE alkylphenyl ethers such as POE (10) 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 amphoteric surfactants that can be incorporated into the ionic SHCL eye drops of the present invention include alkyldiaminoethylglycine. Specific examples of the cationic surfactant that can be added to the ionic SHCL eye drops of the present invention include benzalkonium chloride and benzethonium chloride. Specific examples of anionic surfactants that can be incorporated into the ionic SHCL eye drops of the present invention include alkylbenzene sulfonates, alkyl sulfates, polyoxyethylene alkyl sulfates, aliphatic α-sulfones. Examples include methyl ester and α-olefin sulfonic acid.

  In the ophthalmic solution for ionic SHCL of the present invention, the above surfactants 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; particularly preferably polysorbate 80, polyoxyethylene hydrogenated castor Oil 60, POE-POP block copolymer; more preferably polysorbate 80 is used. According to these preferable surfactants, the effect of suppressing the adsorption of the component (A) to the ionic SHCL can be further improved by providing high safety to the ocular mucosa.

When a surfactant is blended in the ionic SHCL eyedrops 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 use of the eyedrop, etc. It can be set appropriately according to. 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 0.00.
Examples are 5 w / v%, more preferably 0.01 to 0.1 w / v%.

The eye drop for ionic SHCL of the present invention may further contain a buffering agent in addition to the above components. The buffer that can be incorporated into the ionic SHCL eye drops 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, acetate buffer, epsilon-aminocaproic acid, and the like. These buffering agents may be used in combination. Preferred buffering agents are borate buffer, phosphate buffer, and carbonate buffer. A particularly preferred buffer is a borate buffer or a phosphate buffer, and a most preferred buffer is a borate buffer. Examples of the boric acid buffer include borates such as alkali metal borate and alkaline earth metal borate. Examples of the phosphate buffer include phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. More specific examples include boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.
), Phosphoric acid or a salt thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.), Carbonic acid or a salt thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.), acetic acid or a salt thereof (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.), etc. It can be illustrated. These buffering agents may be used alone or in any combination of two or more.

When a buffering agent is blended in the ionic SHCL eyedrops 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 use of the eyedrops, etc. For example, the total amount of the buffer is 0.01 to 10 w / v%, preferably 0.1 to 5 w / v%, Preferably 0.5-2 w / v%
The ratio which becomes is illustrated.

The pH of the eye drops for ionic SHCL of the present invention is not particularly limited as long as it is within a range that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. As an example of pH of the eye drops for ionic SHCL of the present invention, 4.0 to 9.5, preferably 5.0 to 8.5, more preferably 5.0 to 7.5, and more preferably 6.0. The range which becomes -7.5 is mentioned. If the eye drop for ionic SHCL of the present invention is adjusted to be in such a pH range, the effect of suppressing the adsorption of the component (A) to ionic SHCL is effectively retained, and the irritation to the ocular mucosa is reduced. High safety can be provided.

In addition, the osmotic pressure of the ionic SHCL eye drop 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 eye drops for ionic SHCL of the present invention, a range of preferably 0.7 to 5.0, more preferably 0.9 to 3.0, and particularly preferably 1.0 to 2.0. Is 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 the osmotic pressure of 0.9w / v% sodium chloride aqueous solution based on the 15th revised Japanese Pharmacopoeia. Measure with reference to. The standard solution for measuring the osmotic pressure ratio was sodium chloride (Japanese Pharmacopoeia standard reagent) dried at 500-650 ° C for 40-50 minutes, and then allowed to cool in a desiccator (silica gel). Dissolve in water to prepare exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).

The eye drops for ionic SHCL of the present invention may contain an appropriate amount of various pharmacologically active ingredients and physiologically active ingredients in addition to the above-mentioned ingredients 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, examples of the components used in the eye drops for ionic SHCL of the present invention include the following components.
Histamine agent: For example, iproheptin, diphenhydramine and the like.
Decongestant: Tetrahydrozoline, naphazoline, epinephrine, ephedrine, methylephedrine, etc.
Bactericides: for example, acrinol, cetylpyridinium, benzalkonium, benzethonium, chlorhexidine and the like.
Vitamins: flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate, tocopherol acetate, etc.
Amino acids: aminoethylsulfonic acid and the like.
Anti-inflammatory agents: for example, glycyrrhetinic acid, pranoprofen, methyl salicylate, glycol salicylate, allantoin, azulene, azulenesulfonic acid, guaiazulene, tranexamic acid, ε-aminocaproic acid, berberine, lysozyme, licorice, etc.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Other: for example, ketotifen fumarate, sodium cromoglycate, sulfamethoxazole, indomethacin, ibuprofen, ibuprofen piconol, bufexamac, butyl fenfenam, bendazac, piroxicam, ketoprofen, felbinac, purple root, tochinoki and their salts etc.

In addition, for the eye drops for ionic SHCL of the present invention, various additives can be appropriately selected according to conventional methods according to its use and form, as long as the effects of the invention are not impaired, and one or more The above may be used in combination to contain an appropriate amount. Examples of such additives include various additives described in Pharmaceutical Additives Encyclopedia 2005 (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, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol and the like.
Sugars: for example, glucose, cyclodextrin and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.
Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, etc.), Glowyl (manufactured by Rhodia) Name) etc.
pH adjuster: for example, hydrochloric acid, boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, borax, tri Ethanolamine, 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 and the like.
Isotonizing agents: for example, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, dihydrogen phosphate Sodium, sodium dihydrogen phosphate, potassium dihydrogen phosphate, glycerin, propylene glycol and the like.
Stabilizer: Dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, etc.
Perfume or refreshing agent: 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 eye drops for ionic SHCL of the present invention, for example, in the aqueous carrier such as purified water, physiological saline, etc., the above components (A) and (B), if necessary, other compounding components at a desired concentration And prepared according to a conventional method.

In the eye drops for ionic SHCL of the present invention, the type of ionic SHCL to be applied is not particularly limited, and all ionic SHCL currently marketed or marketed in the future can be applied. In addition, ionicity here means that the ionic component content rate in a raw material is 1 mol% or more according to the US FDA standard so that those skilled in the art usually understand. Further, the water content of the ionic SHCL to be applied is not particularly limited, and examples thereof include 90% or less, preferably 60% or less, more preferably 50% or less, and particularly preferably 40% 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.

  Compared to non-silicone hydrogel contact lenses, which are generally soft materials, SHCL, which is a hard material, tends to cause deterioration of the feeling of use due to deformation of the lens due to drug adsorption and reduced wettability, and tends to cause ocular mucosal damage. . According to the eye drop for ionic SHCL of the present invention, adsorption of chlorpheniramine and / or a salt thereof to the hard material SHCL that easily causes deterioration in use feeling and ocular mucosa damage can be effectively suppressed. , Thereby preventing lens deformation and wettability deterioration, and can effectively prevent deterioration of feeling of use and ocular mucosal damage. 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 eye drop for ionic SHCL of the present invention. Preferably, the hardness of the ionic SHCL to be applied is 4 g or more, more preferably 6 g or more, and 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.

Contact lens hardness is measured with a texture analyzer (Product name: TA.XT.plus TEXTURE
Using ANALYSER (manufactured by Stable Micro Systems Limited)), it can be measured specifically as follows.

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 usage form of the eye drop for ionic SHCL of the present invention includes a form in which the eye drop is directly applied to the eye wearing the ionic SHCL, and a form in which the eye drop is put on before the ionic SHCL is attached.

The eye drops for ionic SHCL of the present invention can also exhibit an antihistaminic action based on the above component (A), and thus are useful as a preventive or alleviating agent for allergic symptoms.

(II) A method for suppressing adsorption of chlorpheniramine and / or a salt thereof to ionic SHCL; to impart an action of suppressing the adsorption of chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens to an eye drop Method: Method for suppressing deformation of ionic SHCL by chlorpheniramine and / or salt thereof; and imparting action to eye drops to suppress deformation of ionic silicone hydrogel contact lens by chlorpheniramine and / or salt thereof And a method for producing eye drops, as described above, by coexisting the component (B) together with the component (A) in the eye drops for ionic SHCL, the above (A) for ionic SHCL Adsorption of components can be suppressed.

Therefore, the present invention, from yet another viewpoint, is at least one selected from the group consisting of (A) chlorpheniramine and a salt thereof, and (B) at least selected from the group consisting of a polycarboxylic acid and a salt thereof. Provided is a method for suppressing adsorption of chlorpheniramine and / or a salt thereof to ionic SHCL, which is used in combination with one kind. Further, the present invention provides an eye drop for an ionic silicone hydrogel contact lens containing at least one selected from the group consisting of (A) chlorpheniramine and a salt thereof, from (B) a polycarboxylic acid and a salt thereof. Provided is a method for imparting an eye drop with an action of suppressing adsorption of chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens, which comprises blending at least one selected from the group consisting of .

  Furthermore, by allowing the component (B) to coexist with the component (A) in the eye drops for ionic SHCL, deformation of the ionic SHCL caused by the component (A) can be suppressed.

Accordingly, the present invention, from yet another viewpoint, in an ionic SHCL eye drop, (A) at least one selected from the group consisting of chlorpheniramine and a salt thereof, and (B) a polycarboxylic acid and a salt thereof A method for suppressing the deformation of ionic SHCL by chlorpheniramine and / or a salt thereof, comprising using at least one selected from the group consisting of: The present invention also provides (A) eye drops for ionic silicone hydrogel contact lenses containing at least one selected from the group consisting of chlorpheniramine and salts thereof, (B)
An eye drop having an action of suppressing deformation of an ionic silicone hydrogel contact lens by chlorpheniramine and / or a salt thereof, comprising at least one selected from the group consisting of a polycarboxylic acid and a salt thereof Provide a method of granting.

Further, the present invention, from yet another viewpoint, (A) at least one selected from the group consisting of chlorpheniramine and a salt thereof and (B) at least one selected from the group consisting of a polycarboxylic acid and a salt thereof. Also provided is a use for the manufacture of eye drops for ionic SHCL.

In these methods and uses, the types of the components (A) and (B) to be used, the blending ratio in the eye drops for ionic SHCL, the types and concentrations of other ingredients, and the preparation of eye drops for ionic SHCL The form, type of ionic SHCL to be applied, and the like are the same as in the above “(I) Eye drops for ionic SHCL”.

(III) Chlorpheniramine to ionic silicone hydrogel contact lenses and
Agent for suppressing adsorption of salt and / or agent, and agent for suppressing deformation of ionic silicone hydrogel contact lens by chlorpheniramine and / or salt thereof Adsorption of the component (A) can be suppressed by the component (B). Accordingly, the present invention, from still another aspect, (A) chlorpheniramine to an ionic silicone hydrogel contact lens containing at least one selected from the group consisting of (B) a polycarboxylic acid and a salt thereof And / or an agent for suppressing adsorption of the salt thereof.

  Furthermore, as described above, deformation of the ionic SHCL due to the component (A) can be suppressed by the component (B). Accordingly, the present invention, from still another aspect, (B) an ionic silicone hydrogel contact with chlorpheniramine and / or a salt thereof containing at least one selected from the group consisting of a polycarboxylic acid and a salt thereof An agent for suppressing deformation of a lens is provided.

In these agents, the type of component (B) which is an active ingredient, ionic SHCL to be applied,
The type of the component (A) adsorbed on the ionic SHCL, the type of the component (A) that deforms the ionic SHCL, and the like are the same as those in the “(I) eye drops for ionic SHCL”.

  Hereinafter, the present invention will be described in detail based on test examples, examples, and the like, but the present invention is not limited thereto. In the test solutions shown in the following Table 2-10 (Example 1-24 and Comparative Example 1-5), the remainder other than the display components is purified water.

Reference Test Example 1: Evaluation of Adsorption Characteristics of Chlorpheniramine Maleate on Various SCLs The following experiment was conducted using the four types of soft contact lenses shown in Table 1 to each soft contact lens of chlorpheniramine maleate. The adsorption characteristics of were evaluated. The soft contact lenses used in this test are all commercially available products. When the hardness of each soft contact lens was measured using a texture analyzer (product name: TA.XT.plus TEXTURE ANALYSER (manufactured by Stable Micro Systems Limited)) as described above, the hardness of lens A was 3.04 g. The hardness of lens B was 6.67 g, the hardness of lens C was 2.28 g, and the hardness of lens D was 10.51 g.

  Specifically, it was evaluated by the following method. One soft contact lens was immersed in 10 mL of the test solution shown in Table 2 and shaken at 34 ° C. for 24 hours. Next, the amount of chlorpheniramine maleate remaining in each test solution was measured using HPLC according to a conventional method. Further, as a blank, 10 mL of the test solution was shaken at 34 ° C. for 24 hours without immersing the soft contact lens, and the amount of chlorpheniramine maleate remaining in the test solution was similarly measured using HPLC (blank group). . By subtracting the amount of chlorpheniramine maleate remaining in the test solution in which each soft contact lens was immersed from the amount of chlorpheniramine maleate remaining in the test solution of the blank group, chlorpheniyl maleate adsorbed on each contact lens was subtracted. The amount of lamin (μg / CL) was calculated.

The obtained results are shown in FIG. As is clear from FIG. 1, an ionic non-silicone hydrogel lens (lens C) compared to a nonionic non-silicone hydrogel lens (lens A) and a nonionic silicone hydrogel lens (lens B). ) And ionic silicone hydrogel lenses (lens D), chloropheniramine maleate was significantly adsorbed.

Test Example 1: Adsorption inhibition evaluation of chlorpheniramine maleate-1
Using the test solutions shown in Table 3 (Example 1 and Comparative Example 1), an ionic non-silicone hydrogel lens (see Table 1) in which remarkable adsorption of chlorpheniramine maleate was observed in Reference Test Example 1 above. The adsorbed amount of chlorpheniramine maleate on the contact lens with respect to the lens C) and the ionic silicone hydrogel lens (lens D shown in Table 1) was measured. The specific measurement conditions were the same as in Reference Test Example 1, and the adsorption amount was determined by subtracting the value of the blank group in which the lens was not immersed. The ratio of the adsorption amount of chlorpheniramine maleate in the test solution of the example to the adsorption amount of chlorpheniramine maleate in the test solution of the comparative example was determined, and the adsorption inhibition rate (%) of chlorpheniramine maleate was calculated.

The obtained results are shown in FIG. In the test solution of Example 1, the adsorption of chlorpheniramine maleate to the ionic non-silicone hydrogel lens (lens C) was shown to tend to be accelerated, whereas the ionic silicone hydrogel lens. For (Lens D), it was revealed that the adsorption of chlorpheniramine maleate was significantly suppressed. In addition, when the Student's t-test was performed about this test result, the significant difference was recognized (** P <0.01).

  From the above results, sodium chondroitin sulfate has an action of suppressing the adsorption of chlorpheniramine maleate to ionic SHCL, and such an adsorption suppressing action is not observed for ionic non-silicone hydrogel lenses. It was revealed that this was a unique action observed in ionic SHCL.

Test Example 2: Adsorption suppression evaluation-2 of chlorpheniramine maleate
Using the test solutions shown in Table 4 (Example 2-4 and Comparative Example 1), the effect of suppressing the adsorption of chlorpheniramine maleate to the ionic silicone hydrogel lens (lens D shown in Table 1), Evaluation was performed in the same manner as in Test Example 1.

  The obtained results are shown in FIG. As is apparent from FIG. 3, the adsorption of chlorpheniramine maleate to ionic SHCL was suppressed in a dose-dependent manner with sodium chondroitin sulfate. In addition, as with sodium chondroitin sulfate, it was revealed that the adsorption of chlorpheniramine maleate to ionic SHCL can be remarkably suppressed when sodium hyaluronate is used.

  From the above results, it was confirmed that the adsorption of chlorpheniramine maleate to ionic SHCL can be effectively suppressed by chondroitin sulfate, hyaluronic acid, and salts thereof.

Test Example 3: Adsorption inhibition evaluation of chlorpheniramine maleate-3
Using the test solutions shown in Table 5 (Examples 5-9 and Comparative Example 1), the effect of suppressing the adsorption of chlorpheniramine maleate to ionic silicone hydrogel lenses (lens D shown in Table 1), Evaluation was performed in the same manner as in Test Example 1.

  The obtained results are shown in FIG. From this result, it was confirmed that glycyrrhizic acid, aspartic acid, alginic acid, citric acid, and salts thereof have an action of significantly suppressing adsorption of chlorpheniramine maleate to ionic SHCL.

Test Example 4: Adsorption inhibition evaluation 4 of chlorpheniramine maleate
Using the test solutions shown in Table 6 (Examples 10-17 and Comparative Example 1), the effect of suppressing the adsorption of chlorpheniramine maleate to the ionic silicone hydrogel lens (lens D shown in Table 1), Evaluation was performed in the same manner as in Test Example 1.

  The obtained results are shown in FIG. From this result, it was found that glycyrrhizic acid, aspartic acid, and salts thereof suppress the adsorption of chlorpheniramine maleate to ionic SHCL in a dose-dependent manner.

Test Example 5: Lens deformation suppression evaluation The effect of suppressing the deformation of the ionic silicone hydrogel contact lens caused by chlorpheniramine maleate was evaluated.

Specifically, it was evaluated by the following method. One ionic silicone hydrogel contact lens (lens D shown in Table 1) was immersed in 10 mL each of the test solutions shown in Table 7 (Comparative Example 1 and Example 6) and shaken at 34 ° C. for 24 hours. As a control, the same test was performed by immersing one lens D in 10 mL of physiological saline (0.9% sodium chloride solution). Each test solution or physiological saline is changed every 24 hours. Seven days after the start of the test, the lens size is changed to a universal projector (product name: PROFILE PROJECTOR V-12B, manufactured by Nikon) in each test solution or physiological saline. It was measured by.

The obtained result is shown in FIG. As is clear from FIG. 6, it was confirmed that in the test solution of Comparative Example 1, the size of the ionic silicone hydrogel contact lens was greatly swollen and deformed by chlorpheniramine maleate. On the other hand, in the test solution of Example 6 formulated by combining L-magnesium and potassium aspartate with chlorpheniramine maleate, lens size deformation due to chlorpheniramine maleate was suppressed, and when physiological saline was used (control) It was confirmed that deformation can be suppressed to the same level as).

Test Example 6: Adsorption inhibition evaluation of chlorpheniramine maleate-5
Using the test solutions shown in Table 8 (Example 18 and Comparative Example 2), the effect of suppressing the adsorption of chlorpheniramine maleate to ionic silicone hydrogel lenses (lens D shown in Table 1) was tested as described above. Evaluation was performed in the same manner as in Example 1.

  The obtained results are shown in FIG. From this result, even when using a phosphate buffer, it was confirmed that the adsorption of chlorpheniramine maleate to ionic SHCL could be suppressed by using magnesium L-aspartate / potassium as in the above test example. It was done.

Test Example 7: Evaluation of adsorption inhibition of chlorpheniramine maleate-6
Using the test solutions shown in Table 9 (Examples 19-21 and Comparative Example 3), the effect of suppressing the adsorption of chlorpheniramine maleate to the ionic silicone hydrogel lens (lens D shown in Table 1), Evaluation was performed in the same manner as in Test Example 1.

  The obtained result is shown in FIG. From this result, even when the blending ratio and blending ratio of each component were changed, sodium chondroitin sulfate, magnesium potassium L-aspartate, and dipotassium glycyrrhizinate were similar to maleic acid for ionic SHCL, as in the above test examples. It was confirmed that adsorption of chlorpheniramine can be suppressed.

Test Example 8: Evaluation of adsorption inhibition of chlorpheniramine maleate-7
The effect which suppresses adsorption | suction of the chlorpheniramine maleate with respect to an ionic silicone hydrogel lens (the lens D shown in Table 1) using the test liquid (Example 22-24 and Comparative Example 4-5) shown in Table 10. Was evaluated in the same manner as in Test Example 1 above. In addition, the adsorption | suction suppression rate (%) of the chlorpheniramine maleate of each Example calculates | requires the ratio of the adsorption amount in each Example with respect to the adsorption amount in the comparative example (comparative example 4 or 5) of the same pH, respectively. Was calculated.

The obtained results are shown in FIG. From this result, even when the pH is 5 to 6, the adsorption of chlorpheniramine maleate to ionic SHCL by using sodium chondroitin sulfate and magnesium L-aspartate / potassium as in the previous test examples It was confirmed that it can be suppressed.

General Consideration From the results of Test Examples 1-4 and 6-8 above, chlorphenic acid maleate against ionic SHCL by chondroitin sulfate, hyaluronic acid, alginic acid, glycyrrhizic acid, aspartic acid, citric acid, and salts thereof. It was revealed that the adsorption of lamin can be remarkably suppressed. These components are all polycarboxylic acids, and it is estimated from this test result that the effect of suppressing the adsorption of chlorpheniramine maleate to ionic SHCL can be achieved from the polycarboxylic acids. In addition, from the results of Test Example 5, it was confirmed that the lens deformation of ionic SHCL caused by chlorpheniramine maleate can be effectively suppressed by using aspartic acid which is one of polycarboxylic acids. Considering that the lens deformation of ionic SHCL is due to adsorption of chlorpheniramine maleate, the results of these test examples show that polycarboxylic acids have ionic SHCL caused by chlorpheniramine maleate. It is also clear that there is an effect of suppressing the lens deformation.

Formulation Examples Eye drops for ionic SHCL (Examples 25-46) are prepared according to the formulations described in Tables 11 and 12.

Claims (6)

(A) at least one selected from the group consisting of chlorpheniramine and a salt thereof;
(B) containing at least one selected from the group consisting of polycarboxylic acids and salts thereof,
pH is 5 to 8.5,
A method for suppressing adsorption of chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens.   The method for inhibiting adsorption according to claim 1, wherein the blending ratio of component (A) is 0.001 to 0.1 w / v%.   The method for suppressing adsorption according to claim 1 or 2, wherein the blending ratio of component (B) is 0.0001 to 10 w / v%.   The ratio of the component (B) to the component (A) is 0.025 to 2000 parts by weight of the total amount of the component (B) per 1 part by weight of the total amount of the component (A). Method. (A) at least one selected from the group consisting of chlorpheniramine and a salt thereof;
(B) containing at least one selected from the group consisting of polycarboxylic acids and salts thereof,
pH is 5 to 8.5,
A method for producing an eye drop for an ionic silicone hydrogel contact lens provided with an action of suppressing adsorption of chlorpheniramine and / or a salt thereof to the ionic silicone hydrogel contact lens. (B) containing at least one selected from the group consisting of polycarboxylic acids and salts thereof,
pH is 5 to 8.5,
An agent for suppressing adsorption of (A) chlorpheniramine and / or a salt thereof to an ionic silicone hydrogel contact lens.

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