JP2017165778A - Ophthalmic composition for silicone hydrogel contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition for a silicone hydrogel contact lens which can inhibit adsorption of dibutylhydroxytoluene and/or butylhydroxyanisole to the silicone hydrogel contact lens.SOLUTION: There is prepared an ophthalmic composition for a silicone hydrogel contact lens by blending (A) dibutylhydroxytoluene and/or butylhydroxyanisole and (B) at least one selected from the group consisting of hydroxypropyl methylcelluloses, hyaluronic acids and tocopherols.SELECTED DRAWING: None

Description

  The present invention relates to an ophthalmic composition for a silicone hydrogel contact lens in which adsorption of these components to the silicone hydrogel contact lens is suppressed while containing dibutylhydroxytoluene and / or butylhydroxyanisole. The present invention also relates to a method for suppressing adsorption of dibutylhydroxytoluene and / or butylhydroxyanisole to a silicone hydrogel contact lens.

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

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

  In general, it is indispensable to design an ophthalmic composition used for a contact lens, taking into account the safety and other effects according to the type of contact lens. In particular, since soft contact lenses are made of different materials, it is important that the ophthalmic composition used for the soft contact lens is designed according to the characteristics of the target soft contact lens.

  On the other hand, dibutylhydroxytoluene and / or butylhydroxyanisole is well known as an antioxidant and is widely used as an additive blended in foods and pharmaceuticals (Patent Documents 1 and 2). Hydroxypropylmethylcelluloses and hyaluronic acids are used as thickening agents to improve drug retention and enhance bioavailability and water retention effect. Tocopherols promote metabolism. It is widely used in ophthalmic compositions as a vitamin preparation.

  However, until now, it has not been known at all about the influence of dibutylhydroxytoluene and / or butylhydroxyanisole on silicone hydrogel contact lenses. Moreover, the effects of applying dibutylhydroxytoluene and / or butylhydroxyanisole to hydroxypropylmethylcelluloses, hyaluronic acids and / or tocopherols in silicone hydrogel contact lenses are completely inferred from the prior art. The current situation is not even possible.

Japanese Patent No. 3021312 JP 2007-99697 A

  The present inventor has examined various effects of dibutylhydroxytoluene and / or butylhydroxyanisole on various soft contact lenses. These components are referred to as silicone hydrogel contact lenses (hereinafter referred to as “SHCL”). I obtained a completely new finding that it adsorbs remarkably. If the composition of eye drops is adsorbed to the soft contact lens in this way, there is a concern about the effect of the adsorbed component remaining on the lens, as well as a decrease in wettability and discoloration of the soft contact lens, a decrease in light transmittance, deformation, etc. There is a risk of causing.

  Therefore, development of a means for effectively suppressing the adsorption of dibutylhydroxytoluene and / or butylhydroxyanisole on SHCL is required.

  As a result of diligent studies to solve the above problems, the present inventor has used SHCL in combination with hydroxybutyl methylcellulose, hyaluronic acid, and / or tocopherols together with dibutylhydroxytoluene and / or butylhydroxyanisole. It was found that the adsorption of dibutylhydroxytoluene and / or butylhydroxyanisole with respect to the water can be remarkably suppressed, and the decrease in wettability of SHCL can be suppressed. The present invention has been completed by making further improvements based on such findings.

That is, the present invention provides the following ophthalmic compositions for silicone hydrogel contact lenses.
Item 1-1. (A) at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole, and (B) at least one selected from the group consisting of hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols An ophthalmic composition for silicone hydrogel contact lenses.
Item 1-2. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-1, which contains dibutylhydroxytoluene as the component (A).
Item 1-3. Item 1. The ophthalmic composition for a silicone hydrogel contact lens according to Item 1-1 or Item 1-2, wherein the total amount of the component (A) is 0.00005 to 0.05 w / v%.
Item 1-4. Item (B) The silicone hydrogel contact lens according to any one of Items 1-1 to 1-3, comprising at least one selected from the group consisting of hydroxypropylmethylcellulose, sodium hyaluronate, and tocopherol acetate as component (B) Ophthalmic composition.
Item 1-5. Item 5. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-4, wherein the component (B) is contained in a total amount of 0.0001 to 2 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 surfactant.
Item 1-7. Item 7. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-6, which contains a nonionic surfactant as a surfactant.
Item 1-8. Item 8. The ophthalmic composition for silicone hydrogel contact lens according to Item 1-6 or 1-7, which contains a surfactant in a total amount of 0.001 to 1 w / v%.
Item 1-9. Item 10. The ophthalmic composition for silicone hydrogel contact lens according to any one of Items 1-1 to 1-8, further comprising a buffer.
Item 1-10. Item 10. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-9, which contains a borate buffer as a buffer.
Item 1-11. Item 10. The ophthalmic composition for silicone hydrogel contact lenses according to Item 1-9 or 1-10, comprising a buffering agent in a total amount of 0.01 to 10 w / v%.
Item 1-12. The ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-11, further comprising an isotonic agent.
Item 1-13. The ophthalmology for silicone hydrogel contact lenses according to Item 1-12, which contains at least one selected from the group consisting of sodium chloride, potassium chloride, calcium chloride, magnesium chloride, glycerin, and propylene glycol as an isotonic agent. Composition.
Item 1-14. Item 14. The ophthalmic composition for silicone hydrogel contact lens according to Item 1-12 or 1-13, which contains an isotonic agent in a total amount of 0.01 to 10 w / v%.
Item 1-15. Item 15. An ophthalmic composition for silicone hydrogel contact lenses according to any one of Items 1-1 to 1-14, which is an eye drop.

The present invention also provides the following methods.
Item 2. (A) At least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole and (B) at least one selected from the group consisting of hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols are used in combination A method for suppressing the adsorption of the component (A) to the silicone hydrogel contact lens.
Item 3. (A) An ophthalmic composition for a silicone hydrogel contact lens containing at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole, and (B) hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols At least 1 sort (s) selected from a group is mix | blended, The method to provide the effect | action which suppresses adsorption | suction of this (A) component to a silicone hydrogel contact lens to this ophthalmic composition.
Item 4. (A) At least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole and (B) at least one selected from the group consisting of hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols are used in combination A method for suppressing a decrease in wettability of a silicone hydrogel contact lens that occurs when the component (A) is brought into contact with the silicone hydrogel contact lens.
Item 5. (A) An ophthalmic composition for a silicone hydrogel contact lens containing at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole, and (B) hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols At least one selected from the group, and the action of suppressing the wettability reduction of the silicone hydrogel contact lens that occurs when the component (A) is brought into contact with the silicone hydrogel contact lens A method of applying to an ophthalmic composition.

Furthermore, this invention provides the agent hung up below.
Item 6. (B) A silicone hydrogel contact lens containing at least one selected from the group consisting of hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols. (A) Selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole. An agent for suppressing adsorption of at least one kind.
Item 7. (B) containing at least one selected from the group consisting of hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols, (A) at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole is silicone An agent for suppressing a decrease in wettability of a silicone hydrogel contact lens that occurs when the hydrogel contact lens is brought into contact with the hydrogel contact lens.

  According to the present invention, while containing dibutylhydroxytoluene and / or butylhydroxyanisole, it is possible to effectively suppress these components from adsorbing to SHCL, and there is no concern about a decrease in wettability or coloring, and more comfortable. SHCL ophthalmic compositions that can be used are provided.

In the reference test example 1, it is a figure which shows the result of having evaluated the adsorption | suction characteristic of dibutylhydroxytoluene in various soft contact lenses. In Test Example 1, it is a figure which shows the result of having measured the adsorption amount of the dibutylhydroxytoluene to SHCL using the test liquid (Example 1-3 and Comparative Example 1). In Test Example 2, it is a figure which shows the result of having measured the adsorption amount of dibutylhydroxytoluene to SHCL using a test liquid (Example 4-8 and Comparative Example 2). In Test Example 3, it is a figure which shows the result of having measured the wettability (contact angle; (theta)) of SHCL processed with the test liquid (Example 9-11 and Comparative Example 3-4). In Reference Test Example 2, it is a figure which shows the result of having measured the wettability (contact angle; (theta)) of SHCL processed with the test liquid (Comparative Examples 3 and 5-7). In the reference test example 3, it is a figure which shows the result of having measured the wettability (contact angle; (theta)) of the non-silicone hydrogel contact lens processed with the test liquid (comparative examples 3 and 4).

1. Ophthalmic Composition for SHCL The ophthalmic composition for SHCL of the present invention contains at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole (hereinafter sometimes referred to as component (A)).

  Dibutylhydroxytoluene (chemical name 2,6-di-tert-butyl-4-methylphenol; sometimes abbreviated as BHT) and butylhydroxyanisole (chemical names 2-tert-butyl-4-methoxyphenol and 3- tert-butyl-4-methoxyphenol (sometimes abbreviated as BHA) is a compound in which a t-butyl group is substituted on the benzene ring of hydroxytoluene or hydroxyanisole, and is known as an antioxidant. Dibutylhydroxytoluene and butylhydroxyanisole may be synthesized by a known method or may be obtained as a commercial product.

  In the ophthalmic composition of the present invention, either one of dibutylhydroxytoluene and butylhydroxyanisole may be used alone, or a combination thereof may be used. Among them, although dibutylhydroxytoluene tends to have a large amount of adsorption to SHCL, according to the present invention, it is possible to remarkably suppress the adsorption of dibutylhydroxytoluene that is easily adsorbed to SHCL. In view of the effect of the present invention, the component (A) used in the present invention is preferably dibutylhydroxytoluene.

  In the ophthalmic composition for SHCL of the present invention, the blending ratio of the component (A) may be appropriately set according to the type of the component (A), the formulation form of the ophthalmic composition for SHCL, etc. The total amount of the component (A) is 0.00005 to 0.05 w / v%, preferably 0.0001 to 0.03 w / v%, more preferably 0.0005 to 0, based on the total amount of the ophthalmic composition. .01 w / v% is exemplified.

  In addition to the above component (A), the ophthalmic composition for SHCL of the present invention comprises hydroxypropylmethylcelluloses (hereinafter sometimes referred to as (B-1) component), hyaluronic acids (hereinafter referred to as (B-2) At least one selected from the group consisting of tocopherols (hereinafter also referred to as (B-3) component) (hereinafter referred to as (B-1) to (B-). 3) Ingredients may be collectively referred to as (B) ingredients). By containing the component (B) in this way, it is possible to suppress the adsorption of the component (A) to the SHCL, and consequently suppress the decrease in the wettability of the SHCL caused by the component (A). It becomes possible.

  Hydroxypropylmethylcelluloses used as component (B-1) include hydroxypropylmethylcellulose, derivatives thereof, and salts thereof. Hydroxypropyl methylcellulose is a known compound in which the hydroxy group of cellulose is substituted with a hydroxypropoxy group and a methoxy group, and is widely used as a thickening agent and the like. The content of methoxy group and hydroxypropoxy group in the hydroxypropylmethylcellulose used in the present invention is not particularly limited. For example, the molecule (100% by weight) contains 19 to 31.5% by weight of methoxy group and hydroxy group. The thing which a propoxy group has 4 to 12 weight% is illustrated. Hydroxypropyl methylcellulose may be synthesized by a known method or obtained as a commercial product. Specific examples of hydroxypropylmethylcellulose used in the present invention include hydroxypropylmethylcellulose 2208, hydroxypropylmethylcellulose 2906, hydroxypropylmethylcellulose 2910, hydroxypropylmethylcellulose 1828, and the like.

  The derivative of hydroxypropylmethylcellulose is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specifically, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succin And the like.

  Further, the salt of hydroxypropylmethylcellulose and its derivative is not particularly limited as long as it is in the form of a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable salt. Specifically, Salts with organic bases (for example, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), salts with inorganic bases [for example, ammonium salts; alkali metals ( Sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), salts with metals such as aluminum, etc.]. Among these salts, preferred are salts with inorganic bases, more preferred are alkali metal salts, and still more preferred are sodium salts and / or potassium salts.

  The molecular weight of hydroxypropylmethylcellulose, a derivative thereof, or a salt thereof varies depending on the type of substituent and the degree of substitution, and is not particularly limited, but is usually 10,000 to 1,500,000 in terms of weight average molecular weight, preferably About 50,000 to 1.3 million, more preferably about 10,000 to 1,000,000 can be used.

  In the ophthalmic composition for SHCL of the present invention, when the component (B-1) is used, one of hydroxypropylmethylcellulose, a derivative thereof, and a salt thereof may be selected and used alone. In addition, two or more kinds may be used in any combination. Among these components (B-1), hydroxypropylmethylcellulose is preferably exemplified from the viewpoint of more effectively suppressing the adsorption of the component (A) to SHCL.

  Hyaluronic acids used as the component (B-2) include hyaluronic acid and salts thereof. Hyaluronic acid is a polymer composed of a basic structure (repeat unit) of GlcUA-GlcNAc in which glucuronic acid (GlcUA) and N-acetylglucosamine (GlcNAc) are combined. In the present invention, hyaluronic acid may be a natural product or a synthetic product.

  Moreover, the salt of hyaluronic acid is not particularly limited as long as it is in the form of a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable salt. Salts (eg, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), 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.]. Among these salts, preferred are salts with inorganic bases, more preferred are alkali metal salts, and even more preferred are sodium salts.

  The molecular weight of hyaluronic acid or a salt thereof is not particularly limited, but the average molecular weight is usually from 10 to 5 million, preferably from 10 to 4 million, more preferably from 10 to 3 million, and still more preferably. Of about 100,000 to 2,500,000, particularly preferably about 500,000 to 2,000,000 can be used.

Here, in the present invention, the average molecular weight of hyaluronic acid or a salt thereof means a viscosity average molecular weight. The viscosity average molecular weight can be determined by a known measurement method. Specifically, hyaluronic acid and / or a salt thereof (dried product) is dissolved in a 0.2 M sodium chloride solution, the intrinsic viscosity (η) at 30 ° C. is obtained, and the Laurent equation (η (intrinsic viscosity) = 0. Based on 00003 × Mv (viscosity average molecular weight) ^0.78 ), the viscosity average molecular weight is calculated. The intrinsic viscosity (η) is measured according to the 15th revision Japanese Pharmacopoeia General Test Method Viscosity Measurement Method Method 1: Capillary Viscometer Method.

  In the ophthalmic composition for SHCL of the present invention, when the component (B-2) is used, one of hyaluronic acid and a salt thereof may be selected and used alone, or two or more Any combination of these may be used. Among these components (B-2), from the viewpoint of more effectively suppressing the adsorption of the component (A) to SHCL, a salt of hyaluronic acid, preferably a salt with an inorganic base, more preferably Is an alkali metal salt, particularly preferably a sodium salt (sodium hyaluronate).

  The tocopherols used as the component (B-3) include tocopherol, derivatives thereof, and salts thereof. Tocopherol is a known compound in which a methyl group is substituted for tocol, and is a general-purpose component as vitamin E, which is a fat-soluble vitamin. There are four known tocopherols, α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol depending on the substitution position of the methyl group, and any of them may be used. Moreover, either d body or dl body may be sufficient. The tocopherol is preferably α-tocopherol, more preferably dl-α-tocopherol. Tocopherol may be synthesized by a known method or may be obtained as a commercial product.

  The derivative of tocopherol is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and specifically, tocopherol acetate, tocopherol succinate, tocopherol nicotinate, linolene Examples include tocopherol organic acid esters such as acid tocopherol. Tocopherol acetate is preferred.

  Moreover, the salt of tocopherol and its derivative is not particularly limited as long as it is in the form of a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable salt. Salts (eg, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), 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.]. Among these salts, a salt with an inorganic base is preferable, an alkaline earth metal salt is more preferable, and a calcium salt is more preferable.

  In the ophthalmic composition for SHCL of the present invention, when the component (B-3) is used, one may be selected from tocopherols, derivatives thereof, and salts thereof, and used alone. Two or more kinds may be used in any combination. Among these components (B-3), from the viewpoint of more effectively suppressing the adsorption of the component (A) to SHCL, it is preferably a tocopherol derivative, more preferably a tocopherol organic acid ester, and even more preferably acetic acid. Tocopherol is mentioned.

  In the ophthalmic composition for SHCL of the present invention, as the component (B), one of the above components (B-1) to (B-3) may be used alone, or two or more thereof may be used. Any combination of these may be used. Among these components (B), from the viewpoint of more effectively suppressing the adsorption of the component (A) to SHCL, preferably the component (B-3), more preferably a tocopherol organic acid ester, more preferably Tocopherol acetate is exemplified.

In the ophthalmic composition for SHCL of the present invention, the blending ratio of component (B) is appropriately set according to the type of component (A), the type of component (B), the formulation form of the ophthalmic composition for SHCL, etc. However, as an example, the total amount of component (B) is 0.0001 to 2 w / v%, preferably 0.01 to 0.5 w / v%.
More specifically, the following ranges are exemplified as the blending ratio of each component (B) with respect to the total amount of the ophthalmic composition for SHCL:
When it is the component (B-1), the total amount of the component (B-1) is 0.001 to 2 w / v%, preferably 0.005 to 1 w / v%, more preferably 0.05 to 0.5 w / v. v%;
When it is the component (B-2), the total amount of the component (B-2) is 0.0001 to 1 w / v%, preferably 0.001 to 0.5 w / v%, more preferably 0.01 to 0. 2w / v%;
When it is the component (B-3), the total amount of the component (B-3) is 0.0001 to 0.3 w / v%, preferably 0.001 to 0.2 w / v%, more preferably 0.01 to 0.1 w / v%.

Further, in the ophthalmic composition for SHCL of the present invention, the ratio of the component (B) to the component (A) is not particularly limited, but the adsorption of the component (A) to the SHCL is more effectively suppressed. From the viewpoint of, the range in which the total amount of the component (B) is 2 to 400000 parts by weight, preferably 100 to 100000 parts by weight is exemplified. More specifically, the following ranges are exemplified as the ratio of each component (B) per 100 parts by weight of the total amount of component (A):
Component (B-1) is 20 to 400,000 parts by weight in total, preferably 100 to 200,000 parts by weight, more preferably 1000 to 100,000 parts by weight;
Component (B-2) has a total amount of 2 to 200000 parts by weight, preferably 20 to 100000 parts by weight, more preferably 200 to 20000 parts by weight;
Component (B-3) is 2 to 40,000 parts by weight, preferably 20 to 20000 parts by weight, more preferably 100 to 10,000 parts by weight in total.

  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, preferably nonionic surfactants; more preferably POE sorbitan fatty acid esters, POE hydrogenated castor oil, or POE / POP block copolymers; more preferably POE sorbitan fatty acid esters, POE Hardened castor oils; polysorbate 80 and polyoxyethylene hardened castor oil 60 are particularly preferably used.

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

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

  When a buffering agent is blended with the ophthalmic composition for SHCL of the present invention, the blending ratio of the buffering agent depends on the type of buffering agent used, the type and amount of other blending components, the formulation form of the ophthalmic composition, etc. Depending on the total amount of the ophthalmic composition for SHCL, for example, the total amount of the buffer is 0.01 to 10 w / v%, preferably 0.1 to 5 w / Examples are v%, more preferably 0.5 to 2.5 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, glycerin, propylene glycol, sodium chloride, potassium chloride, calcium chloride, and magnesium chloride are preferable from the viewpoint of achieving the effect of the present invention more surely, and more preferably. Sodium chloride or glycerin is mentioned, Especially preferably, sodium chloride is mentioned. 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, chlorpheniramine maleate, ketotifen fumarate, pemirolast potassium and the like.
Decongestant: For example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline sulfate, epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, and the like.
Fungicide: For example, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, polyhexamethylene biguanide hydrochloride, and the like.
Vitamins: For example, flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate and the like.
Amino acids: For example, potassium aspartate, magnesium aspartate, aminoethylsulfonic acid and the like.
Anti-inflammatory agents: for example, dipotassium glycyrrhizinate, pranoprofen, allantoin, azulene, sodium azulenesulfonate, guaiazulene, ε-aminocaproic acid, berberine chloride, berberine sulfate, lysozyme chloride, licorice, etc.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Other: For example, sodium cromoglycate, sodium chondroitin sulfate, sulfamethoxazole, sulfamethoxazole sodium and the like.

In addition, in the ophthalmic composition for 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. Examples of these additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Carrier: An aqueous carrier such as water or hydrous ethanol.
Thickener: For example, carboxyvinyl polymer, hydroxyethylcellulose, 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, BR> A polyhexamethylene biguanide, etc.), glowul (rhodia) Company name).
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, eye drops for SHCL are preparations that are frequently used per day, and the above component (A) tends to be adsorbed in large quantities on SHCL. According to the present invention, it is possible to effectively suppress the adsorption of the component (A) even in such an eye drop in which the component (A) easily adsorbs. In view of such a point of view, 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. Here, ionic refers to the content of ionic components in contact lens materials of 1 mol% or more in accordance with US FDA (US Food and Drug Administration) standards, and nonionic refers to US FDA ( According to US Food and Drug Administration standards, the content of ionic components in contact lens materials is less than 1 mol%. Further, the moisture content of SHCL to be applied is not particularly limited, and examples thereof include 90% or less, preferably 60% or less, and more preferably 50% or less. Since SHCL contains a hydrogel material, it contains at least more than 0% moisture.

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

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

2. Method for inhibiting adsorption of dibutylhydroxytoluene and / or butylhydroxyanisole on SHCL; and method for inhibiting reduction in wettability of SHCL caused by dibutylhydroxytoluene and / or butylhydroxyanisole As described above, component (A) above on SHCL Can be suppressed by the component (B). In addition, the decrease in the wettability of SHCL due to the adsorption of the component (A) to the SHCL can be suppressed by the component (B).

  Accordingly, the present invention, from yet another point of view, comprises (A) at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole, and (B) hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols. Provided is a method for suppressing adsorption of the component (A) to SHCL, which comprises using at least one selected from the group. Further, the present invention provides (B) hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols in an ophthalmic composition for SHCL containing (A) at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole. There is also provided a method for imparting to the ophthalmic composition an action of suppressing the adsorption of the component (A) to SHCL, wherein at least one selected from the group consisting of:

  Further, the present invention provides (A) at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole, and (B) at least selected from the group consisting of hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols. Provided is a method for suppressing a decrease in wettability of SHCL that occurs when the component (A) is brought into contact with SHCL. Further, the present invention provides (B) hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols in an ophthalmic composition for SHCL containing (A) at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole. At least one selected from the group consisting of: and imparting to the ophthalmic composition an action of suppressing reduction in wettability of SHCL that occurs when the component (A) is brought into contact with SHCL A method is also provided.

  In the method, the types and blending ratios of the components (A) and (B), the types and blending ratios of the other blending ingredients, the dosage form of the ophthalmic composition for SHCL, the types of SHCL to be applied, etc. 1. The same as “SHCL ophthalmic composition”.

3. Agent for suppressing adsorption of dibutylhydroxytoluene and / or butylhydroxyanisole on SHCL; and agent for suppressing reduction in wettability of SHCL caused by dibutylhydroxytoluene and / or butylhydroxyanisole As described above, SHCL Adsorption of the component (A) on the surface can be suppressed by the component (B). In addition, the decrease in the wettability of SHCL due to the adsorption of the component (A) to the SHCL can be suppressed by the component (B).

  Therefore, the present invention, from yet another viewpoint, contains (B) hydroxybutyl methylcellulose, hyaluronic acid, and tocopherols as an active ingredient, and (A) dibutyl to SHCL, which contains at least one selected from the group consisting of An agent for suppressing adsorption of at least one selected from the group consisting of hydroxytoluene and butylhydroxyanisole is provided.

  Furthermore, the present invention includes (B) a group consisting of (A) dibutylhydroxytoluene and butylhydroxyanisole, containing as an active ingredient at least one selected from the group consisting of (B) hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols. Provided is an agent for suppressing a decrease in wettability of SHCL that occurs when at least one selected from contact with SHCL.

  In this agent, the type of component (B) as an active ingredient, the SHCL to be applied, the type of component (A), the blending ratio thereof, and the like are the same as those in “1. SHCL ophthalmic composition”. .

  Hereinafter, the present invention will be described in detail based on examples and the like, but the present invention is not limited to these examples.

Reference Test Example 1: Dibutylhydroxytoluene (BHT) adsorption test Using various SCLs, the adsorption amount of BHT was evaluated by the following method. The SCL used in the test is specifically a lens shown in Table 1 below.

  First, the surface of each lens is sufficiently rinsed with physiological saline, and then each lens is immersed in 5 ml of a BHT combination test solution shown in Table 2 one by one and immersed for about 2 hours at 37 ° C. and 120 rpm. Treatment was performed (sample group). In addition, a blank group was prepared by shaking the same BHT combination test solution without immersing any SCL. Two hours later, the amount of BHT contained in the test solution of the sample group and the blank group was quantified by an HPLC method according to a conventional method, and the amount of BHT adsorbed on each SCL was calculated from the difference.

  The results are shown in FIG. As is clear from FIG. 1, BHT adsorption was hardly observed on two types of conventional hydrogel lenses (lenses C and D; non-silicone hydrogel lenses). On the other hand, it was observed that a large amount of BHT was adsorbed to two types of SHCL (lenses A and B). From this result, it became clear that there is a specific problem that SHCL easily adsorbs BHT.

Test Example 1: BHT adsorption inhibition test (1)
As SHCL, the lens A (SHCL) used in Reference Test Example 1 was used, and the BHT adsorption suppression effect was evaluated.

  First, according to Table 3, each test solution (Example 1-3, Comparative Example 1) was prepared. Next, after rinsing the surface of the lens A sufficiently with physiological saline, the lens A is immersed one by one in 5 ml of each test solution shown in Table 3 and immersed for about 2 hours at 37 ° C. and 120 rpm. (Sample group). In addition, a blank group was prepared by shaking only 5 ml of each test solution without immersing the lens A. Two hours later, the amount of BHT contained in the test solution of the sample group and the blank group was quantified by an HPLC method according to a conventional method, and the amount of BHT adsorbed on SHCL when each test solution was used was calculated from the difference.

  The results are shown in FIG. As is clear from FIG. 2, in the test solution containing only dibutylhydroxytoluene (Comparative Example 1), it was confirmed that a large amount of BHT was adsorbed on SHCL as in Reference Test Example 1 above. On the other hand, in the test solution (Example 1-3) containing a combination of dibutylhydroxytoluene and hydroxypropylmethylcellulose, sodium hyaluronate, or tocopherol acetate, it becomes clear that the adsorption of BHT to SHCL is remarkably suppressed. It was.

Test example 2: BHT adsorption inhibition test (2)
In the same manner as in Test Example 1, the test solution (Example 4-8, Comparative Example 2) shown in Table 4 was evaluated for the effect of suppressing the adsorption of BHT to the lens A (SHCL).

  The results are shown in FIG. As is clear from FIG. 3, when hydroxypropylmethylcellulose, sodium hyaluronate, or tocopherol acetate was used (Example 4-6), the adsorption of BHT to SHCL was remarkably suppressed as in Test Example 1 above. It was recognized that It was also revealed that when two of these components were used in combination (Examples 7-8), the amount of BHT adsorbed could be further reduced.

Test Example 3: SHCL wettability evaluation test (1)
The following lens E was used as SHCL, and the influence of BHT adsorption and suppression on the wettability of SHCL was evaluated.

  First, according to Table 6, each test solution (Example 9-11, Comparative Example 3-4) was prepared. Next, the surface of the lens E was sufficiently rinsed with physiological saline, and then immersed one by one in 20 ml of each test solution, followed by shaking treatment at room temperature for 24 hours. After 24 hours, the lens E is taken out, the surface moisture is gently wiped off, and 1.0 μL of physiological saline using a contact angle measuring device: Drop Master 500 and analysis software: FAMAS (both manufactured by Kyowa Interface Science Co., Ltd.) The contact angle (θ) when water was dropped on the lens surface was measured. The measurement point was set at 1500 ms, the measurement was performed 5 times per lens, and the average value was calculated.

  The results are shown in FIG. As is clear from FIG. 4, the contact angle of SHCL treated with the test solution containing only BHT (Comparative Example 4) is significantly increased compared to the SHCL treated with the test solution corresponding to the control (Comparative Example 3). It became clear that. Since an increase in the contact angle of SHCL is an index indicating a decrease in the wettability of SHCL, it has been found that the adsorption of BHT to SHCL significantly reduces the wettability of SHCL. On the other hand, in SHCL treated with BHT, hydroxypropyl methylcellulose, sodium hyaluronate, tocopherol acetate combined with a test solution (Example 9-11), the increase in contact angle is remarkably suppressed, and the wettability deteriorates due to BHT. It became clear that it was able to suppress effectively.

Reference test example 2: SHCL wettability evaluation test (2)
As the SHCL, the lens E (SHCL) used in Test Example 3 was used, and the influence of hydroxypropylmethylcellulose, sodium hyaluronate, or tocopherol acetate itself on the wettability of SHCL was evaluated.

  First, test solutions shown in Table 7 (Comparative Examples 3 and 5-7) were prepared. A test was conducted in the same manner as in Test Example 3 except that the number of lenses E immersed in 20 ml of each test solution was changed to 3, and the contact angle of SHCL was measured.

  The result is shown in FIG. As shown in FIG. 5, compared with the SHCL treated with the test solution of Comparative Example 3, the contact angle of the SHCL treated with the test solution of Comparative Example 5-7 was almost the same. From this result, it was revealed that hydroxypropyl methylcellulose, sodium hyaluronate, or tocopherol acetate itself has little effect on improving the wettability of SHCL.

Reference Test Example 3: Wetability Evaluation Test of Hydrogel Lens As a conventional hydrogel lens, the lens C (non-silicone hydrogel contact lens) used in Reference Test Example 1 is used, and the treatment with BHT affects the wettability of the lens. The impact was evaluated.

  Specifically, test solutions (Comparative Examples 3 and 4) shown in Table 8 were prepared. The test was conducted in the same manner as in Reference Test Example 2 above, and the contact angle of the hydrogel lens was measured.

  The result is shown in FIG. As shown in FIG. 6, in the case of a conventional hydrogel lens, it is clear that no increase in contact angle due to BHT as observed in Test Example 3 was observed, and there was no effect on wettability. became. This result confirms that the difference in the amount of BHT adsorbed between the SHCL and the hydrogel lens (non-silicone hydrogel lens) recognized in Reference Test Example 1 correlates with the wettability of the lens. .

Formulation Examples With the formulation described in Table 9, eye drops for SHCL (Examples 12-16) are prepared.

Claims (1)

  (A) at least one selected from the group consisting of dibutylhydroxytoluene and butylhydroxyanisole, and (B) at least one selected from the group consisting of hydroxypropylmethylcelluloses, hyaluronic acids, and tocopherols An ophthalmic composition for silicone hydrogel contact lenses.

Images