WO2024203572A1

WO2024203572A1 - Copolymer and contact lens treatment solution

Info

Publication number: WO2024203572A1
Application number: PCT/JP2024/010658
Authority: WO
Inventors: 俊祐尾▲崎▼; 規郎岩切
Original assignee: 日油株式会社
Priority date: 2023-03-29
Filing date: 2024-03-19
Publication date: 2024-10-03

Abstract

Provided is a copolymer that can easily impart hydrophilic properties and lubricity properties to the surface of soft contact lenses, and superior long-lastingness to said properties. The copolymer has constituent units represented by formulas (A) and (B). A molar ratio nA of the constituent unit represented by formula (A) in relation to the entirety of the copolymer (P) is 10-80 mol%, a molar ratio nB of the constituent unit represented by formula (B) in relation to the entirety of the copolymer (P) is 20-90 mol%, and the weight-average molecular weight of the copolymer is 10,000-2,000,000. [In formula (A) and formula (B), R1 and R2 individually represent a hydrogen atom or a methyl group. X in formula (A) is O or NR3, R3 being a hydrogen atom or an alkyl group having a carbon number of 1-4. R4O in formula (B) represents an oxyalkylene group having a carbon number of 2-4, R4O including at least two types of oxyalkylene groups with different carbon numbers, an additional form of these may be block or random, and p represents the average number of moles of the oxyalkylene groups added and is a number from 4-100.]

Description

Copolymer and contact lens treatment solution

The present invention relates to a copolymer and a treatment solution for contact lenses.

　Surface treatment agents have been widely proposed that can impart surface hydrophilicity, biocompatibility, antithrombogenicity, etc. due to phosphorylcholine groups by treating the surfaces of various materials with phosphorylcholine group-containing copolymers. Applications include hydrophilization treatment to hydrophobic substrates, antifouling treatment of industrial filter surfaces, and surface treatment to suppress the adsorption of proteins and cells to medical polymer materials. In particular, they have been used in soft contact lenses in recent years.

The comfort of wearing soft contact lenses is closely related to the hydrophilicity and lubricity of the lens surface, and maintaining these properties for a long period of time leads to sustained comfort when worn all day.

　Technologies for maintaining the fit of the lenses include those described in Patent Documents 1 and 2, for example. Patent Document 1 discloses a technique in which soft contact lenses are subjected to plasma treatment and hydrophilized with zwitterionic groups. Patent Document 2 discloses a technique in which a soft contact lens containing reactive groups is chemically reacted with and bonded to a hydrophilic polymer having reactive groups, thereby hydrophilizing the surface of the soft contact lens. These techniques involve treating the soft contact lens itself to impart hydrophilicity to the surface, and because the treatment process is complicated, they require highly controlled manufacturing equipment tailored to the treatment technology, which can be economically disadvantageous.

Technologies for solving such problems are known, for example, from Patent Documents 3, 4, and 5, which incorporate polyethylene glycol or a cellulose-based polymer into a treatment solution for soft contact lenses to impart and enhance hydrophilicity to the surface of soft contact lenses and improve wearing comfort.

Furthermore, phosphorylcholine group-containing polymers have a structure similar to phospholipids derived from biological membranes, and are known to have excellent properties such as being very hydrophilic and having high moisturizing properties. For example, Patent Document 6 discloses a technology that improves the wearing comfort by adding a copolymer of a phosphorylcholine group-containing monomer and butyl methacrylate to a treatment solution for soft contact lenses.

International Publication No. 2010/092686 International Publication No. 2001/074932 International Publication No. 2009/032122 International Publication No. 2012/098653 International Publication No. WO 2008/060798 US Patent Application Publication No. 2009/0100801

However, although contact lenses using the soft contact lens treatment solutions described in Patent Documents 3, 4, 5, and 6 provide excellent comfort when worn at the beginning of use, the copolymer and blended ingredients are not sufficiently adsorbed to the contact lens surface, and the good comfort is only sustained temporarily.

In view of the above problems, the present invention aims to provide a copolymer that can easily impart hydrophilicity and lubricity to the surface of a soft contact lens and maintain these properties for a long period of time, and a contact lens treatment solution using the copolymer.

After extensive research, the inventors discovered that the above-mentioned objectives could be achieved by copolymerizing at least two specific types of monomers, leading to the completion of the present invention.

That is, the present invention comprises the following [1] to [4].
[1] A copolymer having constitutional units represented by the following formulas (A) and (B), in which the molar ratio _nA of the constitutional units represented by the following formula (A) to the entire copolymer is 10 to 80 mol %, the molar ratio _nB of the constitutional units represented by the following formula (B) to the entire copolymer is 20 to 90 mol %, and the weight average molecular weight is 10,000 to 2,000,000.

[In the formulas (A) and (B), R ¹ and R ² each independently represent a hydrogen atom or a methyl group. In formula (A), X represents O or NR ³ , where R ³ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. In formula (B), R ⁴ O represents an oxyalkylene group having 2 to 4 carbon atoms, R ⁴ O contains at least two kinds of oxyalkylene groups having different carbon numbers, and the addition form thereof may be either block or random, and p represents the average number of moles of oxyalkylene groups added, which is a number from 4 to 100.]
[2] The copolymer according to [1], wherein the copolymer has a constitutional unit represented by the following formula (C) or (D), and the sum of the molar ratios nC and _nD of the constitutional units represented by the following formula ( _C ) or (D) relative to the entire copolymer is more than 0 mol% and 50 mol% or less.

[In the formula (C), R ⁵ is H or a methylene group, R ⁶ is an alkyl group having 1 to 5 carbon atoms, or when R ⁵ is a methylene group, an alkylene group having 1 to 5 carbon atoms, the end of which is bonded to R ⁵ to form a cyclic structure. In the formula (D), R ⁷ is a hydrogen atom or a methyl group, Y is O or NR ¹⁰ , where R ¹⁰ is H or an alkyl group having 1 to 4 carbon atoms, when Y is O, E ¹ is a structure represented by formula (E), and when Y is NR ¹⁰ , E ¹ is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a structure represented by formula (E). In the formula (E), R ⁸ is H or an alkyl group having 1 to 4 carbon atoms, and R ⁹ is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms.]
[3] The copolymer according to [1] or [2], wherein the structural unit (A) is a structural unit derived from 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate.
[4] A contact lens treatment solution containing 0.001 w/v % or more and 5.0 w/v % or less of the copolymer (P) according to any one of [1] to [3].

The copolymer of the present invention can impart excellent hydrophilicity and lubricity to the surface of soft contact lenses, and these properties are sustainable. Therefore, the copolymer of the present invention is suitable as a treatment solution for soft contact lenses.

FIG. 1 is a drawing for explaining _wb and _wf in a chromatogram (vertical axis: refractive index intensity, horizontal axis: retention time).

The present invention is explained in detail below.

In this specification, "(meth)acrylate" means "acrylate or methacrylate," and the same applies to other similar terms. In this specification, an alkyl group may be either linear or branched.

In this specification, "all day" refers to the period from when contact lenses are first worn to when they are finished being worn in one day, and is assumed to be 8 to 16 hours of continuous wear. "Long periods" refers to the time contact lenses are worn throughout the day.

In addition, when preferred numerical ranges (e.g., ranges of concentration or weight average molecular weight) are described in stages in this specification, the lower and upper limits can be combined independently. For example, in the description "preferably 10 or more, more preferably 20 or more, and preferably 100 or less, more preferably 90 or less," the "preferred lower limit: 10" and the "more preferred upper limit: 90" can be combined to read "10 or more and 90 or less." Also, in the description "preferably 10 to 100, more preferably 20 to 90," the range can be similarly set to "10 to 90."

Product forms of the composition containing the copolymer of the present invention include compositions that are applied directly to the eye, and compositions used to treat devices worn on the eye, such as contact lenses, and can be specified as follows. Specific examples include contact lens treatment solutions. Further, specific product forms of the contact lens treatment solution of the present invention include contact lens packing solutions (contact lens shipping solutions), contact lens storage solutions, contact lens cleaning solutions, contact lens cleaning and storage solutions, contact lens disinfectants, contact lens wearing agents, etc.

In this specification, shipping solution for soft contact lenses refers to a solution that is sealed in a packaging container such as a blister package together with soft contact lenses when the soft contact lenses are distributed. Since soft contact lenses are generally used in a state where they are swollen with an aqueous solution, the lenses are sealed in a packaging container in a state where they are swollen with an aqueous solution when shipped from the factory so that they can be used immediately.

<Copolymer (P)>
The copolymer (P) of the present invention contains constitutional units represented by the following formulas (A) and (B), the molar ratio _nA of the constitutional units represented by the following formula (A) to the whole copolymer (P) is 10 to 80 mol %, the molar ratio _nB of the constitutional units represented by the following formula (B) to the whole copolymer (P) is 20 to 90 mol %, and the weight average molecular weight is 10,000 to 2,000,000.

In the formulas (A) and (B), R ¹ and R ² each independently represent a hydrogen atom or a methyl group. X in formula (A) is O or NR ³ , where R ³ is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. R ⁴ O in formula (B) represents an oxyalkylene group having 2 to 4 carbon atoms, R ⁴ O contains at least two kinds of oxyalkylene groups having different carbon numbers, and the addition form thereof may be either block or random, and p represents the average number of moles of oxyalkylene groups added and is a number from 4 to 100.

[Structural unit represented by formula (A)]
The copolymer (P) used in the present invention has a constitutional unit represented by general formula (A). The constitutional unit is obtained by polymerizing a monomer having a phosphorylcholine structure represented by the following general formula (a) (hereinafter, also referred to as a "PC monomer"). By including a constitutional unit derived from a PC monomer in the copolymer (P), hydrophilicity can be imparted to the soft contact lens.

In the formulae (A) and (a), R ¹ represents a hydrogen atom or a methyl group, and X represents O or NR ³ , where R ³ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.

The PC monomer is preferably 2-((meth)acryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate, and more preferably 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate (hereinafter also referred to as "2-methacryloyloxyethyl phosphorylcholine") represented by the following formula (a').

The content of the structural unit represented by formula (A) in the copolymer (P) (molar ratio n _A ) is 10-80 mol%, preferably 15-75 mol%, more preferably 25-65 mol%, and even more preferably 30-55%. If the molar ratio n _A is less than 10 mol%, the effect of improving the hydrophilicity of the soft contact lens surface cannot be expected, and if the molar ratio n _A is more than 80 mol%, the content of the structural unit represented by formula (B) is reduced, the adsorption force of the copolymer (P) to the soft contact lens surface is reduced, and the durability of the good wearing feeling is insufficient. In addition, if the molar ratio n _A is 80 mol% or less, the effect of improving the hydrophilicity and lubricity of the soft contact lens surface can be further enhanced by adjusting the ratio of the structural unit represented by formula (A) and the structural unit represented by formula (B).

[Constituent unit represented by formula (B)]
The copolymer (P) used in the present invention has a constitutional unit represented by the following formula (B). The constitutional unit is obtained by polymerizing a monomer represented by the following general formula (b), that is, a monomer having a polyalkylene glycol structure (hereinafter also referred to as "PAG monomer"). By containing a constitutional unit derived from a PAG monomer in the copolymer (P), a good wearing feeling can be sustained when the obtained soft contact lens is worn. In addition, by having a constitutional unit represented by formula (A) and a constitutional unit represented by formula (B), the effect of improving the hydrophilicity and lubricity of the soft contact lens surface is further enhanced.

The copolymer (P) may also contain multiple structural units represented by the following (B) having different values of p.

In the formulae (B) and (b), R2 represents a hydrogen atom or a methyl group, ^{and R4O} ^represents an oxyalkylene group having 2 to 4 carbon atoms, and ^R4O includes at least two types of oxyalkylene groups having different numbers of carbon atoms. Formula (b) is, for example, a polyalkylene glycol mono(meth)acrylate containing at _least two of oxyalkylene groups selected from oxyethylene groups (-CH ₂ CH ₂ O-), oxypropylene groups (-CH(CH ₃ )CH ₂ O-, -CH ₂ CH(CH ₃ )O-), and oxybutylene groups (-CH(CH ₂ CH ₃ )CH ₂ O-, -CH 2 CH(CH ₂ CH ₃ )O-, -CH(CH ₃ )CH(CH ₃ )O-), in which the addition form of R ⁴ O may be either block or random, and p represents the average number of moles of oxyalkylene groups added, p being a number from 4 to 100.

The oxyalkylene groups in formulae (B) and (b) preferably have a form consisting of an oxyethylene group and an oxypropylene group, an oxyethylene group and an oxybutylene group, an oxypropylene group and an oxybutylene group, or an oxypropylene group, an oxyethylene group and an oxybutylene group, and more preferably have a form consisting of an oxyethylene group and an oxypropylene group.

Furthermore, with regard to the number of moles of oxyethylene groups, oxypropylene groups, and oxybutylene groups added, the molar ratio of oxyethylene groups to the number of moles of all oxyalkylene groups added is 0-90%, preferably 40-90%, and more preferably 60-80%. The molar ratio of oxypropylene groups added is 0-70%, more preferably 10-50%, and the molar ratio of oxybutylene groups added is 0-70%, more preferably 0-30%. When the molar ratio of oxyethylene groups added is more than 90%, the ratios of oxypropylene groups and oxybutylene groups are relatively reduced, and the adsorptive force to the contact lens surface is reduced. On the other hand, when the oxypropylene groups and oxybutylene groups exceed 70%, the cohesive force between the copolymers (P) becomes excessive, and the transparency of the resulting contact lens treatment solution and the contact lens after treatment is deteriorated.

The monomer represented by formula (b) is a monomer having a ratio wb/wf of wb to _wf calculated from a chromatogram (vertical axis: refractive index intensity, horizontal axis: retention time) obtained by gel permeation chromatography ( _{GPC) measurement using a differential refractometer} _, _which satisfies the following formula (1):
1.10≦w _b /w _f ≦2.50 (1)
(In formula (1), when the retention time at the maximum peak height (h) in the peak of the chromatogram is _th and two retention times at 1/10 (h _1/10 ) of the maximum peak height are _tf and _tb (where _tf < _tb ), _wf represents the difference between _th and _tf ( _th - _tf ), and _wb represents the difference between _tb and _th ( _tb - _th )) is preferably satisfied (see FIG. 1).

If the _wb / _wf of the monomer (b) is smaller than 1.10, the molecular weight distribution of the monomer (b) may be biased toward the high molecular weight side, the concentration of the polymerizable functional group may be reduced, and the polymerizability of the monomer (b) may be reduced. From the viewpoint of the polymerizability of the monomer (b), the _wb / _wf is preferably 1.20 or more, and more preferably 1.30 or more.

On the other hand, if the _wb / _wf of the monomer (b) is greater than 2.50, the adsorptivity of the copolymer (P) to the surface of a soft contact lens may decrease. Preferably, _wb / _wf is 2.00 or less, more preferably 1.80 or less.

The chromatogram for calculating w _b /w _f (vertical axis: refractive index intensity, horizontal axis: retention time) was obtained by using an EcoSEC GPC calculation program, with a gel permeation chromatography (GPC) system equipped with an HLC-8320GPC (registered trademark), a guard column equipped with a SHODEXKF-G, and three SHODEXKF804L columns in series, a column temperature of 40° C., tetrahydrofuran as a developing solvent flowing at a flow rate of 1 mL/min, and 0.1 mL of a 0.1 wt % tetrahydrofuran solution of polyalkylene glycol mono(meth)acrylate injected.

The content (molar ratio n _B ) of the structural unit represented by formula (B) in copolymer (P) is 20 to 90 mol %, preferably 25 to 85 mol %, more preferably 35 to 75 mol %, and even more preferably 45 to 70 mol %. As described above, since copolymer (P) used in the present invention has a monomer represented by formula (B) as a structural unit, the adsorptive power of copolymer (P) to the surface of a soft contact lens can be improved, and the durability of the wearing comfort can be improved.

The content of the structural unit represented by formula (B) (molar ratio _nB ) is preferably greater than the content of the structural unit represented by formula (A) (molar ratio _nA ). This further enhances the effect of improving the hydrophilicity and lubricity of the soft contact lens surface. The ratio of the molar ratio _nA to the molar ratio _nB ( _nB / _nA ) is preferably 0.5 to 7.0, and more preferably 1.0 to 3.0.

In the formula (B), p is 4 to 100, preferably 5 to 70, and more preferably 7 to 40. If p is less than 4, the adhesive force of the copolymer (P) to the surface of a soft contact lens decreases, and if it is greater than 100, the cohesive force between the copolymers (P) becomes strong, and the transparency of the resulting contact lens treatment solution and the contact lens after treatment deteriorates.

The above formula (b) can be produced by adding ethylene oxide, propylene oxide, or butylene oxide (preferably propylene oxide or ethylene oxide) to a starting material (e.g., 2-hydroxypropyl methacrylate) in the presence of a composite metal cyanide complex catalyst (hereinafter sometimes referred to as "DMC catalyst"). Specifically, the starting material and the DMC catalyst are added to a reaction vessel, and at least two of ethylene oxide, propylene oxide, and butylene oxide (hereinafter collectively referred to as "alkylene oxides having 2 to 4 carbon atoms") are added continuously or intermittently under stirring in an inert gas atmosphere to carry out addition polymerization. The alkylene oxides having 2 to 4 carbon atoms may be added under pressure or at atmospheric pressure.

The reaction temperature for adding an alkylene oxide having 2 to 4 carbon atoms to the starting material is preferably 50°C to 120°C, and more preferably 70°C to 90°C. If the reaction temperature is lower than 50°C, the reaction rate is very slow, and if it is higher than 120°C, problems such as polymerization of the polymerizable groups in the starting material and discoloration occur.

　A known DMC catalyst can be used in the present invention, for example, the DMC catalyst described in JP-A-2022-130139.

A particularly preferred DMC catalyst is Zn(II) ₃ [Co(III)(CN) ₆ ] ₂ (H ₂ O) ₄ (tert-butyl alcohol) ₂ .

The amount of the DMC catalyst used is not particularly limited, but is preferably 0.0001 to 0.1 parts by mass, and more preferably 0.001 to 0.05 parts by mass, per 100 parts by mass of the monomer represented by formula (b). The DMC catalyst may be added to the reaction system all at once at the beginning, or may be added in portions one by one. After the polymerization reaction is completed, the DMC catalyst is removed. The catalyst can be removed by known methods such as filtration, centrifugation, or treatment with a synthetic adsorbent.

In the reaction of adding an alkylene oxide having 2 to 4 carbon atoms to the starting material, other additives may be used. For example, hydroquinone (HQ), hydroquinone monomethyl ether (MQ), 2,6-di-tert-butylhydroxytoluene (BHT), di-tert-butylhydroxyanisole (BHA), α-tocopherol, β-tocopherol, γ-tocopherol, etc., may be added to the reaction system as a polymerization inhibitor. The polymerization inhibitor is preferably MQ and/or BHT, more preferably BHT. The amount of polymerization inhibitor added is preferably 0.001 to 0.3 parts by mass per 100 parts by mass of the total of the starting material (e.g., 2-hydroxypropyl methacrylate) and the alkylene oxide having 2 to 4 carbon atoms. If the amount added is less than 0.001 part by mass, the function of the polymerization inhibitor becomes insufficient, and gelation may occur during the addition of the alkylene oxide having 2 to 4 carbon atoms. If the amount added is more than 0.3 parts by mass, the purity of the resulting compound of formula (1b') may be low.

[Constituent units represented by formulas (C) and (D)]
The copolymer (P) used in the present invention may contain a structural unit represented by the following formula (C) or (D). The structural unit is obtained by polymerizing a monomer represented by the following general formula (c) or (d), respectively. When the copolymer (P) contains (c) or (d), the adhesive force of the copolymer (P) to a soft contact lens is easily maintained depending on the type of contact lens, and a good wearing comfort can be maintained.

In the formulas (C) and (c), R ⁵ is H or a methylene group, R ⁶ is an alkyl group having 1 to 5 carbon atoms, or when R ⁵ is a methylene group, R 6 is an alkylene group having 1 to 5 carbon atoms that is bonded to R ⁵ to form a cyclic structure. In the formulas (D) and (d), R ⁷ is a hydrogen atom or a methyl group, Y is O or NR ¹⁰ , where R ¹⁰ is H or an alkyl group having 1 to 4 carbon atoms, when Y is O, E ¹ is a structure represented by formula (E), and when Y is NR ¹⁰ , E ¹ is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a structure represented by formula (E). In the formula (E), R ⁸ is H or an alkyl group having 1 to 4 carbon atoms, and R ⁹ is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms.

Examples of the monomer represented by formula (c) include N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylformamide, N-vinylacetamide, and N-methyl-N-vinylacetamide.
Examples of the monomer represented by formula (d) include N-methyl(meth)acrylamide, N-ethyl(meth)acrylamide, N-propyl(meth)acrylamide, N-isopropyl(meth)acrylamide, N-butyl(meth)acrylamide, N-tert-butyl(meth)acrylamide, N,N-dimethyl(meth)acrylamide, N,N-diethyl(meth)acrylamide, 2-(acetylamino)ethyl(meth)acrylate, 2-(stearamido)ethyl(meth)acrylate, and 2-palmitamidoethyl(meth)acrylate.

When copolymer (P) contains structural units represented by formula (C) and formula (D), the total content of the structural unit represented by formula (C) (molar ratio n _C ) and the content of the structural unit represented by formula (D) (molar ratio n _D ) in copolymer (P) is preferably more than 0 mol and not more than 50 mol%, and more preferably 10 to 50 mol%.

The monomer in which E ¹ in the formula (d) is the formula (E) is, for example, as described in JP 2017-160380 A, which can be synthesized by an esterification reaction between an alcohol having an amide structure at its terminal and (meth)acrylic acid or (meth)acrylic acid chloride.

[Other monomers]
Copolymer (P) may contain polymerizable monomers other than the PC monomer, PAG monomer, and the structural units represented by (c) or (d) within a range that does not impair the effects of the present invention. The blending ratio of these monomers may be appropriately selected within a range that does not affect the effects of the present invention, but it is preferable that the copolymer (P) is composed only of the PC monomer and PAG monomer.

The other monomers may be, for example, polymerizable monomers selected from linear or branched alkyl (meth)acrylates, cyclic alkyl (meth)acrylates, aromatic group-containing (meth)acrylates, styrene-based monomers, vinyl ether monomers, vinyl ester monomers, hydroxyl group-containing (meth)acrylates, carboxyl group-containing monomers, and sulfonyl group-containing monomers.

Examples of the linear or branched alkyl (meth)acrylate include methyl (meth)acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate, ethylhexyl (meth)acrylate, lauryl (meth)acrylate, stearyl (meth)acrylate, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, and triethylene glycol di(meth)acrylate.
Examples of cyclic alkyl (meth)acrylates include cyclohexyl (meth)acrylate.
Examples of aromatic group-containing (meth)acrylates include benzyl (meth)acrylate and phenoxyethyl (meth)acrylate.
Examples of the styrene monomer include styrene, methylstyrene, and chlorostyrene.
Examples of the vinyl ether monomer include methyl vinyl ether, propyl vinyl ether, butyl vinyl ether, triethylene glycol divinyl ether, and ethylene glycol monovinyl ether.
Examples of vinyl ester monomers include vinyl acetate and vinyl propionate.
Examples of hydrophilic hydroxyl group-containing (meth)acrylates include hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, and glycerol (meth)acrylate.
Examples of the carboxyl group-containing monomer and the sulfonyl group-containing monomer include (meth)acrylic acid, styrenesulfonic acid, and (meth)acryloyloxyphosphonic acid.

[Weight average molecular weight of copolymer (P)]
The weight average molecular weight of the copolymer (P) is 10,000 to 2,000,000, preferably 20,000 or more, more preferably 30,000 or more, even more preferably 40,000 or more, and preferably 1,000,000 or less, more preferably 500,000 or less, and even more preferably 300,000 or less.

If the weight-average molecular weight is less than 10,000, the adhesive force to the soft contact lens surface will decrease, and the effect of the copolymer (P) on the soft contact lens surface may not be sustained. If the weight-average molecular weight is more than 2,000,000, the viscosity may increase, making handling difficult.

The weight average molecular weight of the copolymer (P) is the value measured by gel permeation chromatography (GPC).

[Method for producing copolymer (P)]
The copolymer (P) can be prepared by copolymerizing the above-mentioned monomers. It is usually a random copolymer, but may be an alternating copolymer or a block copolymer in which the monomers are regularly arranged, or may have a graft structure in part.

Specifically, for example, a mixture of the monomers can be subjected to radical polymerization in the presence of a radical polymerization initiator under an inert gas atmosphere such as nitrogen, carbon dioxide, argon, or helium to obtain a copolymer (P).

The radical polymerization method can be carried out by known methods such as bulk polymerization, suspension polymerization, emulsion polymerization, and solution polymerization. Of the radical polymerization methods, solution polymerization is preferred from the viewpoint of purification, etc. The copolymer (P) can be purified by general purification methods such as reprecipitation, dialysis, and ultrafiltration.

Examples of the radical polymerization initiator include an azo-based radical polymerization initiator, an organic peroxide, and a persulfate.
Examples of the azo radical polymerization initiator include 2,2'-azobis(2-methylpropionamidine) dihydrochloride (V-50), 2,2'-azobis(2-diaminopropyl) dihydrochloride, 2,2'-azobis(2-(5-methyl-2-imidazolin-2-yl)propane) dihydrochloride, 4,4'-azobis(4-cyanovaleric acid), 2,2'-azobisisobutyronitrile dihydrate, 2,2'-azobis(2,4-dimethylvaleronitrile), and 2,2'-azobisisobutyronitrile (AIBN).
Examples of organic peroxides include t-butyl peroxyneodecanate (Perbutyl (registered trademark) ND), benzoyl peroxide, diisopropyl peroxydicarbonate, t-butyl peroxy-2-ethylhexanoate, t-butyl peroxypivalate, t-butyl peroxyisobutyrate, lauroyl peroxide, t-butyl peroxydecanoate, and succinic acid peroxide (succinyl peroxide).
Examples of persulfate oxides include ammonium persulfate, potassium persulfate, and sodium persulfate.
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 0.02 to 5.0 parts by mass, and more preferably 0.03 to 3.0 parts by mass, based on 100 parts by mass of the total of the monomers.

The polymerization reaction 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 each monomer composition and is not reactive itself, and examples of the solvent include water, alcohol solvents, ketone solvents, ester solvents, linear or cyclic ether solvents, and nitrogen-containing solvents.
Examples of the alcohol solvent include methanol, ethanol, n-propanol, and isopropanol.
Examples of the ketone solvent include acetone, methyl ethyl ketone, and diethyl ketone.
An example of the ester solvent is ethyl acetate.
Examples of linear or cyclic ether solvents include ethyl cellosolve and tetrahydrofuran.
Examples of nitrogen-containing solvents include acetonitrile, nitromethane, and N-methylpyrrolidone.
Among these solvents, a mixed solvent of water and an alcohol is preferred.

[Concentration of copolymer (P)]
The soft contact lens treatment solution of the present invention has a concentration of copolymer (P) of 0.001 w/v % or more, preferably 0.01 w/v % or more, more preferably 0.05 w/v % or more, and 5.0 w/v % or less, preferably 2.0 w/v % or less, more preferably 1.0 w/v % or less.
If the concentration of the copolymer (P) is less than 0.001 w/v%, the amount of the copolymer (P) added is so small that sufficient hydrophilicity and lubricity and their durability cannot be obtained, whereas if the concentration exceeds 5.0 w/v%, the sterile filtration performed during production may become difficult.

In the present invention, "w/v %" refers to the mass of a certain component in 100 mL of solution, expressed in grams (g). For example, "the treatment solution of the present invention contains 1.0 w/v % copolymer (P)" means that 100 mL of solution contains 1.0 g of copolymer (P).

The solvent used in the treatment solution of the present invention may be water, ethanol, n-propanol, isopropanol, glycerol, alcohol such as propylene glycol, or a mixture of these. Water or a mixture of water and alcohol is preferred, and water is more preferred.

The water used in the contact lens treatment solution of the present invention can be water that is normally used in the manufacture of pharmaceuticals and medical devices. Specifically, ion-exchanged water, purified water, sterilized purified water, distilled water, and water for injection can be used.

[Other ingredients]
In addition to the polymer (P), the contact lens treatment solution of the present invention may contain other ingredients, such as vitamins, amino acids, sugars, thickening agents, cooling agents, inorganic salts, salts of organic acids, acids, bases, antioxidants, stabilizers, preservatives, etc., as necessary.
Examples of vitamins include sodium flavin adenine dinucleotide, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, sodium pantothenate, calcium pantothenate, and the like.
Examples of the amino acids include aspartic acid or a salt thereof, and aminoethylsulfonic acid.
Examples of sugars include glucose, mannitol, sorbitol, xylitol, and trehalose.
Examples of thickening agents include hydroxypropylmethylcellulose and hydroxyethylcellulose.
Examples of the cooling agent include menthol and camphor.
Examples of inorganic salts include sodium chloride, potassium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, anhydrous sodium dihydrogen phosphate, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate.
The salts of organic acids include sodium citrate and the like.
Examples of the acid include phosphoric acid, citric acid, sulfuric acid, acetic acid, hydrochloric acid, and boric acid.
Examples of the base include potassium hydroxide, sodium hydroxide, borax, trishydroxymethylaminomethane, monoethanolamine, and the like.
Examples of the antioxidant include tocopherol acetate and dibutylhydroxytoluene.
Examples of stabilizers include sodium edetate, glycine, and taurine.
Examples of preservatives include benzalkonium chloride, chlorhexidine gluconate, potassium sorbate, methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, polyhexanide hydrochloride, and sulfamexazole.

[pH of contact lens treatment solution]
From the viewpoint of improving the wearing comfort, the pH of the contact lens treatment solution of the present invention is preferably 3.0 to 8.0, more preferably 3.5 to 7.8, even more preferably 4.0 to 7.6, and still more preferably 4.5 to 7.5.
In this specification, the pH of the contact lens treatment solution refers to a value measured in accordance with the 18th Edition of the Japanese Pharmacopoeia, General Test Method 2.54 pH Measurement Method.

[Osmotic pressure and osmotic pressure ratio of contact lens treatment solution]
From the viewpoint of improving the wearing comfort, the osmotic pressure of the contact lens treatment solution of the present invention is preferably 200 to 400 mOsm, more preferably 225 to 375 mOsm, even more preferably 230 to 350 mOsm, and even more preferably 240 to 340 mOsm. The osmotic pressure ratio is preferably 0.7 to 1.4, more preferably 0.7 to 1.3, and even more preferably 0.8 to 1.2.
In this specification, the osmotic pressure of the contact lens treatment solution refers to a value measured in accordance with the 18th Edition of the Japanese Pharmacopoeia, General Test Method 2.47 Osmotic Pressure Measurement Method (Osmolarity Measurement Method), and the osmotic pressure ratio refers to a value obtained by dividing the obtained osmotic pressure value by the osmotic pressure value (286 mOsm) of 0.9 mass % physiological saline solution.

[Method of manufacturing a treatment solution for soft contact lenses]
The soft contact lens treatment solution of the present invention can be produced by a general method for producing a contact lens solution. For example, it can be produced by mixing and stirring the polymer (P), a solvent and other components as necessary. The obtained soft contact lens treatment solution may be subjected to a procedure such as sterilization filtration as necessary.

The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited thereto. The copolymers used in the examples and comparative examples are as follows.

<Synthesis of Compound I represented by formula (b)> [Synthesis Example 1-1]
A 5L autoclave equipped with a thermometer, pressure gauge, safety valve, nitrogen gas inlet tube, stirrer, vacuum exhaust tube, cooling coil, and steam jacket was charged with 500g of 2-hydroxypropyl methacrylate (HPMA), 0.07g of DMC catalyst, and 1.0g of 2,6-di-tert-butylhydroxytoluene (BHT). After nitrogen replacement, the temperature was raised to 80°C, and 403g of propylene oxide (PO) was dropped from the nitrogen gas inlet tube under conditions of 0.3MPa or less, and the changes in pressure and temperature over time in the reaction vessel were measured. After that, the pressure in the reaction vessel suddenly decreased after 5 hours. Thereafter, while maintaining the reaction vessel at 80°C, a mixture of 262g of PO and 870g of ethylene oxide (EO) was gradually dropped from the nitrogen gas inlet tube under conditions of 0.5MPa or less. After the addition was completed, the mixture was reacted at 80° C. for 1 hour, the reaction mixture was extracted from the reaction layer, and the reaction mixture was filtered to remove solids, thereby obtaining a liquid product of the monomer of formula (b) in which 2 moles of PO were added to HPMA, and then 1.3 moles of PO and 5.7 moles of EO were randomly added. The molecular weight distribution was confirmed by GPC, and w _b /w _f was 1.59. The structure was confirmed by ¹ H NMR.
The DMC catalyst used was synthesized according to the procedure described in JP-A-2022-130139.

<Synthesis of Compound II represented by Formula (b)> [Synthesis Example 1-2]
In a 5L autoclave equipped with a thermometer, a pressure gauge, a safety valve, a nitrogen gas inlet tube, a stirrer, a vacuum exhaust tube, a cooling coil, and a steam jacket, 520g of HPMA, 0.08g of DMC catalyst, and 1.0g of BHT were charged. After nitrogen replacement, the temperature was raised to 80°C, and 419g of PO was dropped from the nitrogen gas inlet tube under conditions of 0.3MPa or less, and the changes in pressure and temperature in the reaction vessel over time were measured. After 5 hours, the pressure in the reaction vessel suddenly decreased. Then, while maintaining the reaction vessel at 80°C, a mixture of 1111g of EO was gradually dropped from the nitrogen gas inlet tube under conditions of 0.5MPa or less. After the addition was completed, the reaction was carried out at 80°C for 1 hour, the reaction mixture was extracted from the reaction layer, and the reaction mixture was filtered to remove the solid, and a liquid product of the monomer of formula (b) in which 2 moles of PO were added to HPMA and then 7 moles of EO were added was obtained. The molecular weight distribution was confirmed by GPC, and w _b /w _f was found to be 1.75. The structure was confirmed by ¹ H NMR.

<Synthesis of MAEM represented by (d)> [Synthesis Example 1-3]
9.28 g of 2-acetamidoethanol and 100 mL of dehydrated dichloromethane were added to a 250 mL flask equipped with a thermometer, a gas inlet tube, a stirrer, and a dropping funnel. The flask was thoroughly replaced with argon gas, and then 13.15 g of triethylamine was added. The system was then cooled to -15°C, and 11.29 g of methacrylic acid chloride was slowly dropped from the dropping funnel while watching the thermometer so that the temperature was maintained at about -9°C. After the dropwise addition was completed, the mixture was stirred at room temperature for 3 hours. The reaction mixture was filtered to remove the precipitate, and the filtrate was washed with water, a saturated aqueous solution of sodium bicarbonate, and a saturated aqueous solution of sodium chloride in that order, and then dried with sodium sulfate. The mixture was concentrated under reduced pressure with a rotary evaporator to obtain an oily product. The mixture was further purified by silica gel chromatography using hexane and ethyl acetate as eluents, and the example compound 2-(acetylamino)ethyl methacrylate was obtained. The structure was confirmed by ¹ H NMR.
2-(acetylamino)ethyl methacrylate (MAEM) was synthesized according to the procedure described in JP-A-2017-160380.

<Copolymer (P)>
In the examples, the following copolymers 1 to 6 were used as working polymers.

MPC: 2-methacryloyloxyethyl phosphorylcholine (product of NOF Corporation)
Compound I: polyethylene glycol-polypropylene glycol monomethacrylate (random adduct of PO and EO (PO/EO=3.3/5.7 mol), p≈10, w _b /w _f =1.59, synthesized in Synthesis Example 1-1)
Compound II: polyethylene glycol-polypropylene glycol monomethacrylate (block adduct of PO and EO (PO/EO=2.0/7.0 mol), p≈10, w _b /w _f =1.75, synthesized in Synthesis Example 1-2)
MAEM: 2-(acetylamino)ethyl methacrylate (synthesized in Synthesis Example 1-3)
NVP: N-vinylpyrrolidone (product of Fujifilm Wako Pure Chemical Industries, Ltd.)
Table 1 summarizes the corresponding formulas of the compounds used.

<Measurement of weight average molecular weight>
1 mg of the copolymer obtained was dissolved in 1 g of mobile phase and measured. Other measurement conditions were as follows.
Column: SB-802.5 HQ + SB-806MN HQ + SB-G
Mobile phase: 20 mM phosphate buffer (pH 7.0)
Standard substance: polyethylene glycol/oxide Measuring instrument: HLC-8320GPC (manufactured by Tosoh Corporation)
Calculation method of weight average molecular weight: Molecular weight calculation program (EcoSEC Date Analysis)
Flow rate: 0.5 mL per minute
Injection volume: 100 μL
Column oven: 45°C
Measurement time: 90 minutes

<Polymerization of Copolymers for Examples>
[Example 1-1]
0.90 g of MPC and 4.18 g of compound I (synthesized in Synthesis Example 1-1) were dissolved in 14.4 g of water and 14.4 g of ethanol, and the solution was placed in a 100 mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2 L/min for 30 minutes (MPC: compound I = 30: 70 (molar ratio)). 0.51 g of Perbutyl (registered trademark) ND (PB-ND, manufactured by NOF Corporation) was added at 55 ° C. and stirred for 3 hours, and then the temperature was raised to 75 ° C. and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.4 g of water was added, distillation was carried out for 1 hour, and the resulting reaction solution was purified by dialysis to obtain a polymer solution (copolymer 1). The weight average molecular weight was confirmed by GPC and was 32,100.

[Example 1-2]
2.20g of MPC and 2.92g of compound I were dissolved in 14.5g of water and 14.5g of ethanol, and the solution was placed in a 100mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2L/min for 30 minutes (MPC: compound I = 60:40 (molar ratio)). 0.51g of PB-ND was added at 55°C and stirred for 3 hours, and then the temperature was raised to 75°C and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.5g of water was added, distillation was carried out for 1 hour, and the resulting reaction solution was purified by dialysis to obtain a polymer solution (copolymer 2). The weight average molecular weight was confirmed by GPC and was 150,500.

[Examples 1-3]
1.70 g of MPC, 5.64 g of compound I, and 0.66 g of MAEM (synthesized in Synthesis Example 1-3) were dissolved in 16.0 g of water and 16.0 g of ethanol, and placed in a 100 mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2 L/min for 30 minutes (MPC: compound I: MAEM = 30: 50: 20 (molar ratio)). 0.40 g of PB-ND was added at 55 ° C. and stirred for 3 hours, and then the temperature was raised to 75 ° C. and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 16.0 g of water was added, distillation was carried out for 1 hour, and the resulting reaction solution was purified by dialysis to obtain a polymer solution (copolymer 3). The weight average molecular weight was confirmed by GPC and was 190,500.

[Examples 1 to 4]
2.20g of MPC, 2.63g of compound I, and 0.33g of NVP were dissolved in 14.6g of water and 14.6g of ethanol, and placed in a 100mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2L/min for 30 minutes (MPC: compound I: NVP = 50: 30: 20 (molar ratio)). 0.52g of PB-ND was added at 55°C and stirred for 3 hours, and then the temperature was raised to 75°C and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.6g of water was added, distillation was carried out for 1 hour, and the resulting reaction solution was purified by dialysis to obtain a polymer solution (copolymer 4). The weight average molecular weight was confirmed by GPC and was 100,500.

[Examples 1 to 5]
0.50g of MPC, 4.31g of compound I, and 0.39g of MAEM were dissolved in 14.7g of water and 14.7g of ethanol, and placed in a 100mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2L/min for 30 minutes (MPC: compound I: MAEM = 15:65:20 (molar ratio)). 0.52g of PB-ND was added at 55°C and stirred for 3 hours, and then the temperature was raised to 75°C and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.7g of water was added, distillation was carried out for 1 hour, and the resulting reaction solution was purified by dialysis to obtain a polymer solution (copolymer 5). The weight average molecular weight was confirmed by GPC and was 29,500.

[Examples 1 to 6]
0.90 g of MPC and 4.22 g of compound II (synthesized in Synthesis Example 1-2) were dissolved in 14.5 g of water and 14.5 g of ethanol, and the solution was placed in a 100 mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2 L/min for 30 minutes (MPC: compound II = 30: 70 (molar ratio)). 0.51 g of PB-ND was added at 55 ° C. and stirred for 3 hours, and then the temperature was raised to 75 ° C. and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.5 g of water was added, distillation was carried out for 1 hour, and the resulting reaction solution was purified by dialysis to obtain a polymer solution (copolymer 6). The weight average molecular weight was confirmed by GPC and was 98,500.

<Copolymer for comparative example>
In the comparative examples, the following homopolymers 1 and 2, copolymers 7 and 8, and PVP K30 (polyvinylpyrrolidone K30) were used as comparative polymers.

<Polymerization of Comparative Copolymer>
[Comparative Example 1-1]
5.00 g of MPC was dissolved in 14.2 g of water and 14.2 g of ethanol, and the solution was placed in a 100 mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2 L/min for 30 minutes. 0.50 g of PB-ND was added at 55°C and stirred for 3 hours, and then the temperature was raised to 75°C and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.2 g of water was added, and distillation was carried out for 1 hour. The resulting reaction solution was purified by dialysis to obtain a polymer solution (homocopolymer 1). The weight average molecular weight was confirmed by GPC and was 300,000.

[Comparative Example 1-2]
5.10 g of compound I was dissolved in 14.5 g of water and 14.5 g of ethanol, and the solution was placed in a 100 mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2 L/min for 30 minutes. 0.51 g of PB-ND was added at 55°C and stirred for 3 hours, and then the temperature was raised to 75°C and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.5 g of water was added, and distillation was carried out for 1 hour. The resulting reaction solution was purified by dialysis to obtain a polymer solution (homocopolymer 2). The weight average molecular weight was confirmed by GPC and was 20,000.

[Comparative Example 1-3]
3.30 g of MPC and 1.91 g of MAEM were dissolved in 14.8 g of water and 14.8 g of ethanol, and the solution was placed in a 100 mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2 L/min for 30 minutes (MPC:MAEM=50:50 (molar ratio)). 0.52 g of PB-ND was added at 55° C. and stirred for 3 hours, and then the temperature was raised to 75° C. and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.8 g of water was added, and distillation was carried out for 1 hour. The resulting reaction solution was purified by dialysis to obtain a polymer solution (copolymer 7). The weight average molecular weight was confirmed by GPC and was 53,600.

[Comparative Examples 1 to 4]
3.50 g of MPC and 1.54 g of 2-hydroxyethyl methacrylate (HEMA) were dissolved in 14.3 g of water and 14.3 g of ethanol, and the solution was placed in a 100 mL four-neck flask, and nitrogen was blown in at a flow rate of 0.2 L/min for 30 minutes (MPC:HEMA=50:50 (molar ratio)). 0.50 g of PB-ND was added at 55°C and stirred for 3 hours, and then the temperature was raised to 75°C and polymerization reaction was carried out for another 2 hours. After the reaction was completed, 14.3 g of water was added, and distillation was carried out for 1 hour. The resulting reaction solution was purified by dialysis to obtain a polymer solution (copolymer 8). The weight average molecular weight was confirmed by GPC and was 356,000.

<Test contact lenses used in evaluation>
Lens A: One Day Fine UV Plus, a soft contact lens (a product of Seed Co., Ltd.)
Lens B: AQUAFORCE UV, a soft contact lens (a product of Aimi Co., Ltd.)

<Preparation of physiological saline solution>
A physiological saline solution was prepared with reference to the literature (ISO 18369-3:2017, Ophthalmic Optics-Contact Lenses Part 3: Measurement Methods.).
8.3 g of sodium chloride, 5.993 g of sodium hydrogen phosphate dodecahydrate, and 0.528 g of sodium dihydrogen phosphate dihydrate were weighed out, dissolved in water to make 1000 mL, and filtered to make physiological saline solution.

<Preparation of treatment solution for soft contact lenses>
<Example 2-1>
The solution of copolymer 1 was dissolved in a predetermined amount of physiological saline to prepare a 5 wt % polymer solution as shown in Table 2 below. Furthermore, 2 g of the polymer solution was mixed with 98 g of physiological saline to prepare a contact lens treatment solution as shown in Table 2 below. Test contact lenses treated with this contact lens treatment solution were evaluated for hydrophilicity, lubricity and durability. The evaluation results are shown in Table 2 below.

<Examples 2-2 to 2-9>
The hydrophilicity, lubricity and durability of test contact lenses treated with contact lens treatment solutions prepared according to the same procedure as in Example 1 were evaluated, except that the polymers shown in Tables 2 and 3 were used. The evaluation results are shown in Tables 2 and 3.

<Comparative Examples 2-1 to 2-5>
Except for using the polymer and PVP K30 shown in Table 4 below, the contact lenses were treated with the contact lens treatment solutions prepared in the same manner as in Example 1, and the hydrophilicity, lubricity and durability of the treated contact lenses were evaluated. The evaluation results are shown in Table 4 below.

<Evaluation of hydrophilicity>
In the Examples and Comparative Examples, the surface hydrophilicity of the soft contact lenses was evaluated according to the following procedure: Surface hydrophilicity evaluation assuming the start of wearing the soft contact lenses (1) 10 mL of physiological saline was added to a 15 mL conical tube, and five test contact lenses removed from the blister pack were immersed in the solution, and the lenses were shaken at room temperature for 6 hours at a rotation speed of 50 rpm using a roller mixer.
(2) The test contact lenses were taken out and each was placed in a 10 mL glass vial containing 5 mL of the prepared soft contact lens treatment solution.
(3) The container was sterilized at 121°C for 20 minutes.
(4) The test contact lens was removed from the glass vial, and the time (BUT) until the water film on the lens surface disappeared was measured with a stopwatch and evaluated according to the following criteria.

○ Evaluation of surface hydrophilicity of soft contact lenses at the end of wearing period (1) 10 mL of physiological saline was added to a 15 mL conical tube, and five test contact lenses removed from their blister packs were immersed in the solution and shaken at room temperature for 6 hours at a rotation speed of 50 rpm using a roller mixer.
(2) The test contact lenses were taken out and each was placed in a 10 mL glass vial containing 5 mL of the prepared soft contact lens treatment solution.
(3) The container was sterilized at 121°C for 20 minutes.
(4) 2 mL of physiological saline was added to one well of a 12-well plate, and one test contact lens taken out of the glass vial was immersed in the saline solution, followed by shaking at 80 rpm at 37° C. for 4 hours using a shaker.
(5) The test contact lenses were removed from the 12-well plate, and the time (BUT) until the water film on the lens surface disappeared was measured with a stopwatch and evaluated according to the following criteria.

The evaluation assuming the end of wearing takes into account the actual tear volume and blink rate throughout the day, and estimates the condition of the contact lenses after wearing them all day (12 hours of continuous wear).

The evaluation criteria are as follows:
4 points: 20 seconds or more 3 points: 15 seconds or more 2 points: 10 seconds or more but less than 15 seconds 1 point: 5 seconds or more but less than 10 seconds 0 point: Less than 5 seconds

<Lubricity evaluation>
In the Examples and Comparative Examples, the lubricity evaluation of the contact lenses was carried out according to the following procedure: Lubricity evaluation assuming the start of wearing soft contact lenses (1) 10 mL of physiological saline was added to a 15 mL conical tube, and five test contact lenses removed from a blister pack were immersed in the solution, and the solution was shaken at room temperature for 6 hours at a rotation speed of 50 rpm using a roller mixer.
(2) The test contact lenses were taken out and each was placed in a 10 mL glass vial containing 5 mL of the prepared soft contact lens treatment solution.
(3) The container was sterilized at 121°C for 20 minutes.
(4) The test contact lens was removed from the glass vial, and the friction coefficient in physiological saline was measured using a nanotribometer NTR3 (probe material: polypropylene, load: 2 mN, movement distance: 1.00 mm, speed: 0.1 mm/s), and the results were evaluated according to the following criteria.

Lubricity evaluation assuming the end of wearing soft contact lenses (1) 10 mL of physiological saline was added to a 15 mL conical tube, and five test contact lenses removed from their blister packs were immersed in the solution, followed by shaking at room temperature for 6 hours at a rotation speed of 50 rpm using a roller mixer.
(2) The test contact lenses were taken out and each was placed in a 10 mL glass vial containing 5 mL of the prepared soft contact lens treatment solution.
(3) The container was sterilized at 121°C for 20 minutes.
(4) 2 mL of physiological saline was added to one well of a 12-well plate, and one test contact lens taken out of the glass vial was immersed in the saline solution, followed by shaking at 80 rpm at 37° C. for 4 hours using a shaker.
(5) The test contact lenses were removed from the 12-well plate, and the friction coefficient was measured using a nanotribometer NTR3 (probe material: polypropylene, load: 2 mN, movement distance: 1.00 mm, speed: 0.1 mm/s) and evaluated according to the following criteria.

The evaluation criteria are as follows:
4 points: less than 0.30 3 points: 0.30 or more, less than 0.5 2 points: 0.50 or more, less than 1.0 1 point: 1.0 or more, less than 1.5 0 point: 1.5 or more

<Sustainability evaluation>
In the examples and comparative examples, the durability was evaluated based on the evaluation results of hydrophilicity and lubricity and was evaluated according to the following criteria.
◎: The scores for the assumed time at the start and end of wearing were the same in both evaluations. 〇: The scores for the assumed time at the start and end of wearing were reduced by 1 point in either evaluation, or the scores for the assumed time at the start and end of wearing were reduced by 1 point in both evaluations. △: The scores for the assumed time at the start and end of wearing were reduced by 2 points in either evaluation. ×: The scores for the assumed time at the start and end of wearing were reduced by 2 points in both evaluations, or the scores for the assumed time at the start and end of wearing were reduced by 3 points or more in either evaluation.

<Wearing comfort evaluation>
Regarding the Examples and Comparative Examples, the wearing comfort was evaluated according to the following criteria based on the evaluation results of hydrophilicity and lubricity assumed at the end of wearing.
Excellent wearing comfort: Hydrophilicity: 4, Lubricity: 4
Hydrophilicity: 4, Lubricity: 3
Hydrophilicity: 3, Lubricity: 4
Comfortable to wear: Hydrophilicity: 3, Lubricity: 3
: Hydrophilicity: 2, Lubricity: 3
: Hydrophilicity: 3, Lubricity: 2
: Hydrophilicity: 2, Lubricity: 2
Insufficient wearing comfort: Other than the above

<Evaluation>
The contact lens treatment solutions of Examples 2-2, 2-4, 2-5, and 2-9 were able to impart excellent hydrophilicity and excellent lubricity to the surface of soft contact lenses at the start and end of wear, and the persistence of these properties was also very good. That is, the contact lens treatment solutions of Examples 2-2, 2-4, 2-5, and 2-9 were able to impart an excellent wearing sensation to soft contact lenses for a long period of time due to their excellent hydrophilicity and lubricity and the persistence of these properties.
The contact lens treatment solutions of Examples 2-7 and 2-8 were able to impart good hydrophilicity and good lubricity to the surface of soft contact lenses at the start and end of wear, and the persistence of these properties was also very good. That is, the contact lens treatment solutions of Examples 2-7 and 2-8 were able to impart good wearing comfort to soft contact lenses for long periods of time due to their good hydrophilicity and good lubricity and the persistence of these properties.
The contact lens treatment solutions of Examples 2-1, 2-3, and 2-6 were able to impart good hydrophilicity and good lubricity to the surface of soft contact lenses at the start and end of wear, and the persistence of these properties was also good. That is, the contact lens treatment solutions of Examples 2-1, 2-3, and 2-6 were able to impart good wearing comfort to soft contact lenses for long periods of time due to their good hydrophilicity and lubricity and the persistence of these properties.
The contact lens treatment solution of Comparative Example 1-1 had good hydrophilicity at the start of use compared to the other Examples, but was significantly inferior in durability.
The contact lens treatment solution of Comparative Example 1-2 had good hydrophilicity as expected at the start of wearing, but did not have sufficient lubricity and was not comfortable to wear.
The contact lens treatment solution of Comparative Example 1-3 had good hydrophilicity as expected at the start of use, but did not have sufficient lubricity, and the durability and wearing comfort were also insufficient.
The contact lens treatment solution of Comparative Example 1-4 had good hydrophilicity as expected at the start of wearing, but did not have sufficient lubricity and was extremely poor in durability.
The contact lens treatment solution of Comparative Example 1-5 provided a good wearing sensation as expected at the beginning of use, but was significantly inferior in durability.

This application claims priority to Japanese Application No. 2023-053617, filed March 29, 2023, and the contents of the specification, claims and drawings of that application are incorporated by reference into this application.

By using the soft contact lens treatment solution of the present invention on soft contact lenses, it is possible to impart excellent wearing comfort to the soft contact lenses all day (for a long period of time).

Claims

A copolymer having constitutional units represented by the following formulas (A) and (B), wherein the molar ratio nA of the constitutional unit represented by the following formula (A) to the whole copolymer (P) is 10 to 80 mol %, the molar ratio nB of the constitutional unit represented by the following formula (B) to the whole copolymer (P) is 20 to 90 mol %, and the weight average molecular weight is 10,000 to 2,000,000.

[In the formulas (A) and (B), R 1 and R 2 each independently represent a hydrogen atom or a methyl group. In formula (A), X represents O or NR 3 , where R 3 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. In formula (B), R 4 O represents an oxyalkylene group having 2 to 4 carbon atoms, R 4 O contains at least two kinds of oxyalkylene groups having different carbon numbers, and the addition form thereof may be either block or random, and p represents the average number of moles of oxyalkylene groups added and is a number from 4 to 100.]
The copolymer (P) has a constitutional unit represented by the following formula (C) or (D), and the molar ratio nC and nD of the constitutional units represented by the following formula (C) or (D) to the whole copolymer (P) is more than 0 mol% and 50 mol% or less. The copolymer according to claim 1.

[In the formula (C), R 5 is H or a methylene group, R 6 is an alkyl group having 1 to 5 carbon atoms, or when R 5 is a methylene group, an alkylene group having 1 to 5 carbon atoms, the end of which is bonded to R 5 to form a cyclic structure. In the formula (D), R 7 is a hydrogen atom or a methyl group, Y is O or NR 10 , where R 10 is H or an alkyl group having 1 to 4 carbon atoms, when Y is O, E 1 is a structure represented by formula (E), and when Y is NR 10 , E 1 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a structure represented by formula (E). In the formula (E), R 8 is H or an alkyl group having 1 to 4 carbon atoms, and R 9 is a hydrogen atom or an alkyl group having 1 to 18 carbon atoms.]
The copolymer according to claim 1 or 2, wherein the structural unit (A) is a structural unit derived from 2-(methacryloyloxy)ethyl 2-(trimethylammonio)ethyl phosphate.
A contact lens treatment solution containing 0.001 w/v % or more and 5.0 w/v % or less of the copolymer (P) according to any one of claims 1 to 3.