JP7099077B2 - Contact lens solution - Google Patents

Description

The present invention relates to a contact lens solution containing a copolymer having a specific structure.

It is said that the number of soft contact lens wearers in Japan in recent years exceeds 10 million, and it has become a widely used medical device in Japan. In addition, due to its ease and convenience, it has been reported that the wearing time of soft contact lenses has become longer, and the average wearing time per day for young soft contact lens wearers is about 14 hours (non-). Patent Document 1). As the average wearing time per day becomes longer, the good wearing feeling of soft contact lenses is often lost, and the current situation is that the market still demands soft contact lenses that maintain good wearing feeling. Is.
In general, it is said that it is important to impart hydrophilicity and lubricity to soft contact lenses in order to provide soft contact lenses having a good wearing feeling (Non-Patent Documents 2 to 3). Therefore, a cleaning solution that can impart hydrophilicity and lubricity to a soft contact lens when the soft contact lens is treated with the cleaning solution has been developed (Patent Document 1). However, these cleaning solutions contain a cationic bactericide, and this cationic bactericide may cause eye disorders such as corneal epithelial disorders. Normally, the concentration of the cationic bactericide contained in the cleaning solution is very low, so it is unlikely that it will cause eye damage, but in order for the user to use it with greater peace of mind, the cationic bactericide is a soft contact lens. It is necessary to prevent adsorption and accumulation in the lens. Therefore, Patent Document 2 discloses a solution for contact lenses that prevents the adsorption of a cationic bactericide.

Special Table 2009-516217 Publication No. Japanese Unexamined Patent Publication No. 2009-175543

Walline J. J. , 2013, Long-term Contact Lens Wear of Children and Teens, Eye & Contact Lens, 39, 283-289. Roba, M.D. , 2011, Friction Measurements on Contact Lenses In Their Operating Environment, Tribol. Let. , 44 (3), 387-397. Norihiko Yokoi, 2009, Mechanism of dry eye feeling when wearing soft contact lenses, Journal of Nippon Contact Lens Society, 51, S33-S35.

However, Patent Document 2 does not describe the above-mentioned wearing feeling of the contact lens, and therefore, a method of imparting a good wearing feeling to the soft contact lens and further imparting an adsorption preventing effect of the cationic bactericide simply. It has been demanded.
An object of the present invention is to provide a solution for contact lenses that imparts durable surface lubricity, surface hydrophilicity, and adsorption inhibitory effect of a cationic bactericide to the contact lens surface by a simple treatment. ..

As a result of diligent research to solve the above-mentioned problems, the present inventors have found that the above-mentioned problems can be solved by a contact lens solution containing a copolymer having at least three different constituent units in a specific ratio. The invention was completed.
That is, the present invention is the following [1] to [2].

［式（ａ）中、Ｘは（ａ１）に示すいずれかの基を表し、Ｙは（ａ２）に示すいずれかの基を表し、Ｚは（ａ３）に示すいずれかの基を表す。式（ａ）～式（ｃ）中、Ｒ^１、Ｒ^２及びＲ^５はそれぞれ独立に水素原子又はメチル基であり、Ｒ^３及びＲ^４はそれぞれ独立に水素原子、メチル基又はエチル基であるか、あるいは互いに結合してモルホリノ基を形成しており、Ｒ^６は炭素数１２～２４の炭化水素基である。］
［２］上記［１］に記載の共重合体（Ｐ）を０．００１～２．０ｗ／ｖ％含有するソフトコンタクトレンズ用溶液。 [1] It has structural units represented by the following formulas (a) to (c), and the molar ratio na: nb: nc of each structural unit is 100: 10 to 400: 2 to 50, and the weight average molecular weight. A solution for contact lenses containing 0.001 to 2.0 w / v% of the polymer (P) having a molecular weight of 5,000 to 5,000,000.

[In the formula (a), X represents any group shown in (a1), Y represents any group shown in (a2), and Z represents any group shown in (a3). In formulas (a) to (c), R ¹ , R ² and R ⁵ are independently hydrogen atoms or methyl groups, and R ³ and R ⁴ are independently hydrogen atoms, methyl groups or ethyl groups, respectively. Alternatively, they are bonded to each other to form a morpholino group, and R6 is a hydrocarbon group having ¹² to 24 carbon atoms. ]
[2] A solution for soft contact lenses containing 0.001 to 2.0 w / v% of the copolymer (P) according to the above [1].

The solution for contact lenses of the present invention can impart durable surface lubricity, surface hydrophilicity, and adsorption suppressing effect of a cationic bactericide to the surface of a contact lens by a simple treatment, and when wearing a contact lens, it can be applied. It is possible to give a good wearing feeling.

Hereinafter, the present invention will be described in more detail.
[Solution for contact lenses]
The contact lens solution of the present invention has structural units represented by the formulas (a) to (c), and the molar ratio na: nb: nc of each structural unit is 100: 10 to 400: 2 to 50. , Contains 0.001 to 2.0 w / v% of the copolymer (P) having a weight average molecular weight of 5,000 to 5,000,000.

In addition, in this specification, "(meth) acrylate" means "acrylate or methacrylate", and the same applies to other similar terms.
Further, in the present specification, when a preferable numerical range (for example, a range of concentration and weight average molecular weight) is described stepwise, each lower limit value and upper limit value can be combined independently. For example, in the description of "preferably 10 to 100, more preferably 20 to 90", "preferable lower limit value: 10" and "more preferable upper limit value: 90" can be combined to obtain "10 to 90". ..

<Copolymer (P)>
The copolymer (P) used in the solution for contact lenses of the present invention has at least three structural units represented by the following formulas (a) to (c), and the molar ratio (constituent ratio) of each structural unit. na: nb: nc is 100: 10 to 400: 2 to 50.

((1) Hydrophilic constituent unit)
The copolymer (P) used in the solution for contact lenses of the present invention has a structural unit represented by the following formula (a) (hereinafter, abbreviated as “hydrophilic structural unit”).

In the above formula (a), R ¹ is a hydrogen atom or a methyl group, X represents any group shown in (a1), Y represents any group shown in (a2), and Z represents (a2). Represents any of the groups shown in a3). Further, in the formula (a), in R ¹ , the copolymer (P) exhibiting a hydrogen atom or a methyl group contains such a hydrophilic constituent unit, so that the copolymer (P) has hydrophilicity. As a result, the contact lens solution containing the copolymer (P) can impart surface lubricity to the contact lens surface.

上記式（ａ’）においてＲ^１、Ｘ、Ｙ、Ｚはそれぞれ、上記式（ａ）のＲ^１、Ｘ、Ｙ、Ｚと同じである。
式（ａ’）で表される親水性単量体として、例えば、Ｎ，Ｎ，Ｎ－トリメチル－Ｎ－（２－ヒドロキシ－３－（メタ）アクリロイルオキシプロピル）アンモニウムクロライド、Ｎ，Ｎ，Ｎ－トリメチル－Ｎ－（２－（メタ）アクリロイルオキシエチル）アンモニウムクロライドなどが挙げられる。 The hydrophilic structural unit in the copolymer (P) is obtained from the hydrophilic monomer represented by the following formula (a') used during the polymerization of the copolymer (P).

In the above formula (a'), R ¹ , X, Y, Z are the same as R ¹ , X, Y, Z in the above formula (a), respectively.
Examples of the hydrophilic monomer represented by the formula (a') include N, N, N-trimethyl-N- (2-hydroxy-3- (meth) acryloyloxypropyl) ammonium chloride, N, N, N. -Trimethyl-N- (2- (meth) acryloyloxyethyl) ammonium chloride and the like can be mentioned.

上記式（ｂ）において、Ｒ^２は水素原子またはメチル基を示し、Ｒ^３及びＲ^４はそれぞれ独立に、水素原子、メチル基、エチル基、又は、互いに結合してモルホリノ基を示す。
共重合体（Ｐ）がアミド構成単位を含むことにより、共重合体（Ｐ）を高分子量化することができる。これにより、該共重合体（Ｐ）は、コンタクトレンズへの密着性が高まる。
共重合体（Ｐ）中のアミド構成単位の割合については、親水性構成単位のモル数ｎ_ａを１００としたときのモル数ｎ_ｂについて、ｎ_ｂ／ｎ_ａ＝１０／１００～４００／１００であり、好ましくは３０／１００～２５０／１００である。ｎ_ｂが大きすぎる場合にはコンタクトレンズ用溶液を製造する際に必要となる無菌ろ過が困難となるおそれがあり、小さすぎる場合にはコンタクトレンズへの密着性が高められず、潤滑性の向上効果が見込めない。 ((2) Amide constituent unit)
The copolymer (P) used in the solution for contact lenses of the present invention has a structural unit represented by the following formula (b) (hereinafter, may be abbreviated as “amide structural unit”).

In the above formula (b), R ² represents a hydrogen atom or a methyl group, and R ³ and R ⁴ each independently represent a hydrogen atom, a methyl group, an ethyl group, or a morpholino group bonded to each other.
When the copolymer (P) contains an amide constituent unit, the copolymer (P) can be made high molecular weight. As a result, the copolymer (P) has higher adhesion to contact lenses.
Regarding the ratio of the amide constituent unit in the copolymer (P), n _b / n _a = 10/100 to 400/100 for the number of moles n _b when the number of moles n _a of the hydrophilic constituent unit is 100. It is preferably 30/100 to 250/100. If n _b is too large, the aseptic filtration required for producing a contact lens solution may be difficult, and if it is too small, the adhesion to the contact lens cannot be improved and the lubricity is improved. No effect can be expected.

式（ｂ’）におけるＲ^２、Ｒ^３及びＲ^４は、それぞれ、式（ｂ）におけるＲ^２、Ｒ^３及びＲ^４と同じである。
上記式（ｂ’）で表されるアミド基含有単量体は、（メタ）アクリルアミド又は（メタ）アクリルアミド誘導体であり、例えば、Ｎ，Ｎ－ジメチル（メタ）アクリルアミド、Ｎ，Ｎ－ジエチル（メタ）アクリルアミド、Ｎ－アクリロイルモルホリン等が挙げられ、中でもＮ，Ｎ－ジメチル（メタ）アクリルアミドが好ましい。 The amide constituent unit in the copolymer (P) is obtained from the amide group-containing monomer represented by the following formula (b') used during the polymerization of the copolymer (P).

R ² , R ³ and R ⁴ in equation (b') are the same as R ² , R ³ and R ⁴ in equation (b), respectively.
The amide group-containing monomer represented by the above formula (b') is (meth) acrylamide or a (meth) acrylamide derivative, and is, for example, N, N-dimethyl (meth) acrylamide, N, N-diethyl (meth). ) Acrylamide, N-acrylloylmorpholine and the like, and N, N-dimethyl (meth) acrylamide is preferable.

上記式（ｃ）において、Ｒ^５は水素原子またはメチル基を示し、Ｒ^６は炭素数１２～２４の一価の炭化水素基を示す。
Ｒ^６は、直鎖、分岐鎖、飽和、不飽和の何れでもよく、例えば、ラウリル基、トリデシル基、ミリスチル基、パルミチル基、イソパルミチル基、ステアリル基、イソステアリル基、オレイル基、オクチルドデシル基、ベヘニル基等が挙げられる。これらの中でも、Ｒ^６は、ラウリル基、ステアリル基、ベヘニル基が好ましく、ラウリル基、ステアリル基がより好ましい。
共重合体（Ｐ）がこのような疎水性構成単位を含むことにより、共重合体（Ｐ）のコンタクトレンズへの吸着性を高め、コンタクトレンズの潤滑性が向上する。 ((3) Hydrophobic constituent unit)
The copolymer (P) used in the solution for contact lenses of the present invention has a structural unit represented by the following formula (c) (hereinafter, may be abbreviated as “hydrophobic structural unit”).

In the above formula (c), R ⁵ represents a hydrogen atom or a methyl group, and R ⁶ represents a monovalent hydrocarbon group having 12 to 24 carbon atoms.
R ⁶ may be linear, branched, saturated or unsaturated, and may be, for example, a lauryl group, a tridecylic group, a myristyl group, a palmityl group, an isopalmityl group, a stearyl group, an isostearyl group, an oleyl group, an octyldodecyl group, and the like. A behenyl group and the like can be mentioned. Among these, ^R6 is preferably a lauryl group, a stearyl group, or a behenyl group, and more preferably a lauryl group or a stearyl group.
When the copolymer (P) contains such a hydrophobic constituent unit, the adsorptivity of the copolymer (P) to the contact lens is enhanced, and the lubricity of the contact lens is improved.

Regarding the ratio of the hydrophobic constituent unit in the copolymer (P), the number of moles n _c when the number of moles n _a of the hydrophilic constituent unit is 100 is n _c / n _a = 2/100 to 50 /. It is 100, preferably 5/100 to 25/100. If n _c is too large, the hydrophilicity of the copolymer (P) is lowered, so that the solubility in an aqueous solution is lowered, which may make it difficult to produce a solution for contact lenses.

式（ｃ’）におけるＲ^５及びＲ^６はそれぞれ、式（ｃ）におけるＲ^５及びＲ^６と同じである。式（ｃ’）で表される疎水性単量体としては、ラウリル（メタ）アクリレート、ステアリル（メタ）アクリレート、ベヘニル（メタ）アクリレート等の直鎖アルキル（メタ）アクリレートが好ましく、ラウリル（メタ）アクリレート、ステアリル（メタ）アクリレートがより好ましい。 The hydrophobic structural unit in the copolymer (P) is obtained from the hydrophobic monomer represented by the following formula (c') used during the polymerization of the copolymer (P).

R ⁵ and R ⁶ in formula (c') are the same as R ⁵ and R ⁶ in formula (c), respectively. As the hydrophobic monomer represented by the formula (c'), linear alkyl (meth) acrylates such as lauryl (meth) acrylate, stearyl (meth) acrylate and behenyl (meth) acrylate are preferable, and lauryl (meth) acrylate is preferable. Acrylate and stearyl (meth) acrylate are more preferable.

<Other building blocks>
The copolymer (P) used in the present invention may contain other structural units other than the structural units represented by the formulas (a) to (c) as long as the effects of the present invention are not impaired. The amount of the other structural units can be appropriately selected as long as it does not affect the effect of the present invention, but when na represented by the formula (a) is 100 in the copolymer (P), the other structural units are used. Is preferably 50 or less in terms of molar ratio, and more preferably 10 or less.

Other building blocks that can be used in the synthesis of the copolymer (P) are formed of other polymerizable monomers described below. The amount of the other polymerizable monomer in the monomer composition used for the polymerization of the copolymer (P) is 50 when the hydrophilic monomer shown in the above (a') is 100 parts by mass. It is preferably parts by mass or less, and more preferably 10 parts by mass or less.
Examples of other polymerizable monomers include linear or branched alkyl (meth) acrylates, cyclic alkyl (meth) acrylates, aromatic group-containing (meth) acrylates, styrene-based monomers, and vinyl ether monomers. , Vinyl ester monomer, hydrophilic hydroxyl group-containing (meth) acrylate can be mentioned.

Examples of the linear or branched alkyl (meth) acrylate include methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, and 2-ethylhexyl (meth) acrylate.
Examples of the cyclic alkyl (meth) acrylate include cyclohexyl (meth) acrylate.
Examples of the aromatic-containing (meth) acrylate include benzyl (meth) acrylate and phenoxyethyl (meth) acrylate.
Examples of the styrene-based monomer include styrene, methylstyrene, chloromethylstyrene and the like.
Examples of the vinyl ether monomer include methyl vinyl ether and butyl vinyl ether.
Examples of the vinyl ester monomer include vinyl acetate and vinyl propionate.
Examples of the hydrophilic hydroxyl group-containing (meth) acrylate include polyethylene glycol (meth) acrylate, polypropylene glycol (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxybutyl (meth) acrylate, and 4-hydroxybutyl. Examples thereof include (meth) acrylate.

<Molecular weight of copolymer (P)>
The weight average molecular weight of the copolymer (P) used in the present invention is 5,000 to 5,000,000, preferably 5,000 to 2,000,000, and more preferably 100,000 to 1, It is 500,000. If the weight average molecular weight is less than 5,000, the adsorptivity of the copolymer to the contact lens surface is not sufficient, so the effect of improving lubricity may not be expected. If it exceeds 5,000,000, the contact lens is contacted. Aseptic filtration required for producing lens solutions may be difficult.
The weight average molecular weight of the copolymer (P) refers to a value measured by gel permeation chromatography (GPC) and can be measured by the method described in Examples.

<Synthesis method of copolymer (P)>
The copolymer (P) used in the present invention can be obtained by radically polymerizing the composition of each of the above monomers. The copolymer (P) is obtained by radically polymerizing the composition of each of the above monomers in the presence of a radical polymerization initiator, in the presence of an inert gas such as nitrogen, carbon dioxide, argon or helium, or in an atmosphere. Can be synthesized by. Examples of the radical polymerization method include known methods such as bulk polymerization, suspension polymerization, emulsion polymerization, and solution polymerization, and solution polymerization is preferable from the viewpoint of purification and the like. The copolymer (P) can be purified by a known purification method such as a reprecipitation method, a dialysis method, or an ultrafiltration method.

Examples of the radical polymerization initiator include azo radical polymerization initiators, organic peroxides, persulfates and the like.
Examples of the azo radical polymerization initiator include 2,2-azobis (2-diaminopropyl) dihydrochloride and 2,2-azobis (2- (5-methyl-2-imidazolin-2-yl) propane) di. Hydrochloride, 4,4-azobis- (4-cyanovaleronitrile), 2,2-azobisisobutyronitrile amide dihydrate, 2,2-azobis (2,4-dimethylvaleronitrile), 2, 2-azobisisobutyronitrile (AIBN) can be mentioned.

Examples of the organic peroxide include t-butylperoxyneodecanate, benzoyl peroxide, diisopropylperoxydicarbonate, t-butylperoxy-2-ethylhexanoate, t-butylperoxypivalate, and t-butylperoxydiisobu. Examples thereof include tilate, lauroyl peroxide, t-butylperoxydecanete, and succinic peroxide peroxide (= succinyl peroxide).
Examples of the persulfated product include ammonium persulfate, potassium persulfate, sodium persulfate and the like.

These radical polymerization initiators can be used alone or in combination of two or more. The amount of the polymerization initiator used is usually 0.001 to 10 parts by mass, preferably 0.01 to 5.0 parts by mass with respect to a total of 100 parts by mass of each monomer used for producing the copolymer (P). Is.

The synthesis of the copolymer (P) can be carried out in the presence of a solvent. The solvent is not particularly limited as long as it dissolves the monomer composition and does not adversely affect the reaction, and is, for example, water, an alcohol solvent, a ketone solvent, an ester solvent, a linear or cyclic ether. Examples thereof include a system solvent and a nitrogen-containing solvent. Preferred are water or alcohol, or a mixed solvent thereof.
Examples of the alcohol solvent include methanol, ethanol, n-propanol, isopropanol and the like.
Examples of the ketone solvent include acetone, methyl ethyl ketone, diethyl ketone and the like.
Examples of the ester solvent include ethyl acetate and the like.
Examples of the linear or cyclic ether solvent include ethyl cell solve, tetrahydrofuran and the like.
Examples of the nitrogen-containing solvent include acetonitrile, nitromethane, N-methylpyrrolidone and the like.

<Concentration of copolymer (P)>
The concentration of the copolymer (P) in the solution for contact lenses of the present invention is 0.001 to 2.0 w / v%, preferably 0.01 to 2.0 w / v%.
In the contact lens solution of the present invention, the copolymer (P) is dissolved in a solvent at 0.001 to 2.0 w / v%, preferably 0.01 to 2.0 w / v%. Can be obtained by If the concentration of the copolymer (P) is less than 0.001 w / v%, the effect of imparting lubricity to the contact lens is not sufficient, and if it exceeds 2.0 w / v%, it is performed when producing a solution for contact lenses. Aseptic filtration may be difficult. As the solvent, alcohol such as water, methanol, ethanol, n-propanol, isopropanol or a mixed solvent thereof can be used.

By using the copolymer (P) in the contact lens solution, the lubricity of the contact lens can be improved, and a good wearing feeling can be imparted to the contact lens wearer. Further, the contact lens solution of the present invention is preferably used as a soft contact lens solution. That is, it is preferable to use it as a solution for soft contact lenses containing 0.001 to 2.0 w / v% of the copolymer (P).

<Other ingredients>
The solution for contact lenses of the present invention can be used for general contact lens solutions as needed in addition to the copolymer (P), vitamins, amino acids, saccharides, thickening agents, refreshing agents, etc. Other components such as inorganic salts, organic acid salts, acids, bases, antioxidants, stabilizers, preservatives and the like can be blended.
Examples of vitamins include flavin adenine dinucleotide sodium, cyanocobalamin, retinyl acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, sodium pantothenate, calcium pantothenate and the like.
Examples of amino acids include aspartic acid or a salt thereof, aminoethyl sulfonic acid and the like.
Examples of the saccharide include glucose, mannitol, sorbitol, xylitol, trehalose and the like.
Examples of the thickening agent include hydroxypropylmethylcellol, hydroxyethylcellulose and the like.
Examples of the refreshing agent include menthol, camphor and the like.

Examples of the inorganic salts include sodium chloride, potassium chloride, sodium hydrogen phosphate, anhydrous sodium dihydrogen phosphate and the like.
Examples of the salt of the organic acid include sodium citrate and the like.
Examples of the acid include phosphoric acid, citric acid, sulfuric acid, acetic acid, hydrochloric acid, boric acid and the like.
Examples of the base include potassium hydroxide, sodium hydroxide, borax, trishydroxymethylaminomethane, monoethanolamine and the like.
Examples of the antioxidant include tocopherol acetate, dibutylhydroxytoluene and the like.
Examples of the stabilizer include sodium edetate, glycine and the like.
Examples of the preservative include benzalkonium chloride, chlorhexidine gluconate, potassium sorbate, polyhexanide hydrochloride and the like.

<Manufacturing method of solution for contact lenses>
The solution for contact lenses of the present invention can be produced by a general method for producing a solution for contact lenses. For example, it can be produced by mixing and stirring the copolymer (P), if necessary, a solvent and other components. The obtained contact lens solution may be subjected to an operation such as aseptic filtration, if necessary.

Specific examples of the product form of the solution for contact lenses of the present invention include the following. Specific examples thereof include shipping liquids for contact lenses, care products for contact lenses, preservative liquids for contact lenses, cleaning liquids for contact lenses, and cleaning and preservative liquids for contact lenses. In the present specification, the shipping liquid for contact lenses is a solution for immersing the contact lens at the time of shipping the contact lens product.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

<Measurement of molecular weight of copolymer>
5 mg of each of the copolymers obtained in Synthesis Examples 1 to 5 below was dissolved in a methanol / chloroform mixed solution (80:20), and the solution further diluted with water was used as a sample solution. The following analysis conditions were used.
Column: PLgel-mixed-C
Standard substance: Polyethylene glycol Detector: Differential refractometer RI-8020 (manufactured by Tosoh Corporation)
Calculation method of weight average molecular weight: Molecular weight calculation program (GPC program for SC-8020)
Flow rate: 1 mL / min
Injection volume: 100 μL
Column oven: Constant temperature around 40 ° C

The weight average molecular weight of the copolymer is a value of the weight average molecular weight measured by a gel permeation chromatograph (GPC) using polyethylene glycol as a standard sample.
A solution obtained by dissolving the obtained copolymer in a methanol / chloroform mixed solution was diluted with water so that the polymer concentration became 0.5% by mass. This liquid was filtered through a 0.45 μm membrane filter and measured.

<Synthesis of copolymer (P)>
[Synthesis Example 1]
Cationic Monomer 1 (Blemmer QA, manufactured by Nichiyu Co., Ltd.) 55.3 g, Stearyl Methacrylate (SMA, manufactured by Nichiyu Co., Ltd.) 20.8 g and N, N-dimethylacrylamide (DMAA, manufactured by KJ Chemicals Co., Ltd.) 7.9 g Was placed in a four-necked flask, dissolved in 116.0 g of n-propanol, and blown with nitrogen gas for 30 minutes. After that, 0.196 g of a polymerization initiator (t-butylperoxyneodymate, perbutyl (registered trademark in Japan) ND (PB-ND), manufactured by NOF CORPORATION) was added, and a polymerization reaction was carried out at 52 ° C. for 8 hours. rice field. After the polymerization reaction, the polymerization solution was added dropwise to 3 liters of diethyl ether with stirring, the precipitated precipitate was filtered, and vacuum dried at room temperature for 48 hours to obtain a powder. The yield was 66.5 g. This was designated as copolymer 1. The weight average molecular weight of the copolymer 1 based on the GPC measurement is 970,000, and the molar ratio of the copolymer components is cation monomer 150 mol%, DMAA 45 mol%, and SMA 5 mol%.

[Synthesis Examples 2 to 5]
Copolymers 2 to 5 were synthesized according to the same procedure as in Synthesis Example 1 except that the components of the type and amount shown in Table 1 of the table below were used. In addition, Table 1 shows the molar ratio, yield and weight average molecular weight of the copolymerized components.

Cationic monomer 1: Blemmer QA (N, N, N-trimethyl-N- (2-hydroxy-3-methacryloyloxypropyl) ammonium chloride), Nikko Co., Ltd. Cationic monomer 2: Light ester DQ-100 (N, N) , N-trimethyl-N- (2-methacryloyloxyethyl) ammonium chloride), DMAA: N, N-dimethylacrylamide manufactured by Kyoeisha Chemical Co., Ltd., LMA: lauryl methacrylate manufactured by KJ Chemicals Co., Ltd., SMA: stearyl manufactured by Nichiyu Co., Ltd. Methacrylate, manufactured by Nichiyu Co., Ltd. Ethanol: manufactured by Wako Pure Chemical Industries, Ltd. n-propanol: manufactured by Wako Pure Chemical Industries, Ltd. PB-ND: t-butylperoxyneodecanete, manufactured by Nichiyu Co., Ltd.

<Polymer other than copolymer (P)>
The polymers (polymers other than the copolymer (P)) used in the comparative example are as follows.
A homopolymer (A): a polymer of dimethylacrylamide [number average molecular weight: 10,000], a product of Sigma-Aldrich Japan (product name: Poly (N, N-dimethylrylamide), DDMAT Terminated) was used in the test.
Homopolymer (B): Homopolymer (B) was synthesized according to the same procedure as in Synthesis Example 1 except that 84.0 g of light ester DQ-100 was used as the monomer. Specifically, 84.0 g of light ester DQ-100 was dissolved in 116.0 g of n-propanol, and nitrogen gas was blown in for 30 minutes. Then, 0.196 g of the polymerization initiator PB-ND was added, and the polymerization reaction was carried out at 52 ° C. for 8 hours. After the polymerization reaction, the polymerization solution was added dropwise to 3 liters of diethyl ether with stirring, the precipitated precipitate was filtered, and vacuum dried at room temperature for 48 hours to obtain a powdery homopolymer (B). The yield was 64.9 g and the weight average molecular weight was 1,500,000.
A product of Sigma-Aldrich Japan (product name: polylauryl methacrylate), which is a polymer of homopolymer (C): lauryl methacrylate [weight average molecular weight: 470,000], was used in the test.

<Preparation of shipping liquid for contact lenses>
The shipping liquids for contact lenses were prepared by the methods described in Examples 1 to 7 and Comparative Examples 1 to 4 below.

[Example 1]
About 80 g of purified water was weighed, copolymer 1 (1 g) was added thereto, and the mixture was stirred and dissolved. After that, purified water was added to the total volume to 100 mL (to make a copolymer solution). After that, 10 mL of this liquid was taken out, the total volume was 100 mL using physiological saline, and aseptic filtration was performed to prepare a sterile shipping liquid for contact lenses. Table 2 shows the appearance and properties of the shipping liquid for contact lenses.

[Examples 2 to 7]
A sterile contact lens shipping solution was prepared according to the same procedure as in Example 1 except that the types and amounts of the components shown in Table 2 were used. Table 2 shows the appearance and properties of each embodiment.

[Comparative Example 1 to Comparative Example 4]
A sterile contact lens shipping solution was prepared according to the same procedure as in Example 1 except that the types and amounts of the components shown in Table 3 were used. Table 3 shows the appearance and properties of each comparative example.

The shipping liquids for contact lenses of each of the above-mentioned Examples and Comparative Examples were evaluated in various ways as shown below, and the results are shown in Tables 4 and 5.

<Preparation of saline solution>
Physiological saline solution was prepared with reference to the literature (ISO 18369-3: 2006, Ophthalmic Optics-Contact Lenses Part 3: Measurement Methods). Weighed 8.3 g of sodium chloride, 5.993 g of sodium hydrogen phosphate dihydrate, and 0.528 g of sodium dihydrogen phosphate dihydrate, dissolved in water to make 1000 mL, and filtered to obtain a physiological saline solution.

<Evaluation of lubricity of contact lenses>
In the shipping liquids for contact lenses of Examples and Comparative Examples, the lubricity of contact lenses was evaluated according to the following procedure. For the evaluation of the lubricity of the contact lens, Medalist Fresh Fit Comfort Moist (registered trademark) (manufactured by Bausch + Lomb Japan) was used as the contact lens.
(procedure)
1) The shipping liquid for contact lenses of Example 1 was used.
2) One test contact lens was removed from the blister pack and placed in a 15 mL centrifuge tube.
3) 10 mL of physiological saline was added thereto, and the mixture was shaken overnight.
4) After that, the physiological saline solution was removed, 10 mL of the solution prepared in 1) was added, and the mixture was shaken overnight.
5) After shaking, the contact lens was taken out and placed on the index finger to evaluate the lubricity. The evaluation was a lubricity evaluation assuming the start of wearing contact lenses.
6) After that, the contact lens was once immersed in the solution prepared in 1), the water film on the surface of the contact lens was wiped off, and the contact lens was placed on the index finger to evaluate the lubricity. The evaluation was a lubricity evaluation assuming that the contact lens was being worn.

The shipping liquids for contact lenses of Examples 2 to 7 and Comparative Examples 1 to 4 were also evaluated according to the above procedure.
The lubricity evaluation method is based on the Medalist Fresh Fit Comfort Moist (registered trademark) that has just been taken out of the blister pack, and the evaluation score is increased if the lubricity is improved, and the evaluation is made if the lubricity is reduced. I tried to lower the score. The evaluation points were given in the range of 1 to 10 points. The lubricity evaluation is shown in Tables 4 and 5.

<Evaluation of surface hydrophilicity of contact lenses>
In the examples and comparative examples, the surface hydrophilicity of the contact lens was evaluated according to the following procedure. The physiological saline solution used in the hydrophilicity evaluation was prepared in the same manner as in the case of the above lubricity evaluation.
(1) One contact lens (medalist Fresh Fit Comfort Moist (registered trademark)) was taken out from the blister pack and placed in a contact lens case. At this time, the shipping liquid in the blister pack was not put in the contact lens case.
(2) 1 mL of physiological saline was placed in a contact lens case, and the contact lens and the physiological saline were sufficiently immersed so as to be compatible with each other.
(3) The physiological saline solution was removed, 1 mL of new physiological saline solution was added again, and the contact lens and the physiological saline solution were sufficiently immersed so as to be compatible with each other.
(4) The physiological saline solution was removed, 1 mL of each solution of the example and the comparative example was placed in a contact lens case, and autoclave treatment (121 ° C., 20 minutes) was performed.
(5) The contact lens was taken out, and the time (BUT) until the water film on the lens surface was cut was measured with a stopwatch. This BUT is shown in Tables 4 and 5 as "surface hydrophilicity". Those having a BUT of 10 seconds or more and less than 15 seconds were regarded as "excellent in surface hydrophilicity", and those having a BUT of 15 seconds or more were regarded as "particularly excellent in surface hydrophilicity". The surface hydrophilicity evaluation of contact lenses is shown in Tables 4 and 5.

<Evaluation of the effect of suppressing the absorption of bactericides on contact lenses>
In Examples and Comparative Examples, the evaluation of the fungicide adsorption inhibitory effect of contact lenses was performed according to the following procedure.
(1) The contact lens was treated by performing the same operations as in (1) to (4) of <Evaluation of surface hydrophilicity of contact lens>.
(2) The contact lens treated in (1) was immersed in a 1 ppm solution of polyhexanide hydrochloride (PHMB) overnight.
(3) The next morning, the absorbance of the PHMB solution after taking out the contact lens was measured at an absorptiometer 237 nm.
(4) The absorbance at 237 nm in the PHMB solution before immersion in the contact lens was measured, and the adsorption rate was determined using the following formula.
PHMB adsorption rate on contact lenses (%) = (AB) / A × 100
A: Absorptivity of PHMB solution before immersion in contact lenses B: Absorbency of PHMB solution after immersion in contact lenses Tables 4 and 5 show the evaluation results of the effect of suppressing the adsorption of bactericides on contact lenses.

The lubricity evaluation of contact lenses in the examples (evaluation assuming the start of wearing) is 5.0 to 9.2, and the lubricity evaluation of contact lenses in the examples (evaluation assuming wearing) is 3.9. It was ~ 6.3. On the other hand, in the evaluation of the lubricity of the contact lens in the comparative example (evaluation assuming the start of wearing), 2.2 to 2.4, and in the evaluation of the lubricity of the contact lens in the comparative example (evaluation assuming the wearing), 2 It was .1 to 2.2.
The surface hydrophilicity evaluation (BUT) of the contact lens in the examples was 10 to 24, and the surface hydrophilicity evaluation (BUT) of the contact lens in the comparative example was 4 to 6.
Further, the adsorption rate of PHMB on the contact lens in the examples was 14 to 23%, and the adsorption rate of PHMB in the comparative example was 55 to 65%.
From the above, it was found that the shipping liquid for contact lenses of the examples was superior in the effect of imparting lubricity, surface hydrophilicity and adsorption prevention property of the cationic bactericide to the contact lens surface as compared with the comparative example.

[Examples 8 to 12]
The mixture was blended in the ratios of Examples 8 to 12 shown in Table 6 and subjected to aseptic filtration to prepare a shipping liquid for contact lenses containing the copolymer of the present invention. The osmotic pressure in Table 6 was measured according to the 17th revised Japanese Pharmacopoeia General Test Method 2.47 osmotic pressure measurement method (osmolal concentration measurement method).
The contact lenses using the shipping liquids for contact lenses of Examples 8 to 12 are excellent in lubricity and surface hydrophilicity, can obtain a good wearing feeling of contact lenses, and adsorb a cationic bactericide. It has an excellent inhibitory effect, and can maintain a good wearing feeling of contact lenses.

The solution for contact lenses of the present invention can easily impart the effect of improving hydrophilicity, the effect of improving lubricity, and the effect of suppressing adsorption of cationic bactericides to contact lenses. Moreover, this good wearing feeling can be sustained for a long time.

Claims (2)

It has structural units represented by the following formulas (a) to (c), and the molar ratio na: nb: nc of each structural unit is 100:10 to 400: 2 to 50, and the weight average molecular weight is 5,. A solution for contact lenses containing 0.001 to 2.0 w / v% of the copolymer (P) which is 000 to 5,000,000.

[In the formula (a), X represents any group shown in (a1), Y represents any group shown in (a2), and Z represents any group shown in (a3). In formulas (a) to (c), R ¹ , R ² and R ⁵ are independently hydrogen atoms or methyl groups, and R ³ and R ⁴ are independently hydrogen atoms, methyl groups or ethyl groups, respectively. Alternatively, they are bonded to each other to form a morpholino group, and R6 is a hydrocarbon group having ¹² to 24 carbon atoms. ] A solution for soft contact lenses containing 0.001 to 2.0 w / v% of the copolymer (P) according to claim 1.