Phosphorylcholine group-containing silicone compound, method for producing same, composition for contact lens, polymer, and contact lens

Abstract

Provided is a phosphorylcholine group-containing silicone compound with which it is possible to produce a contact lens that has good wettability and maintains lubricity of the lens surface even in cases where the contact lens is dried by being worn for a long period of time. The phosphorylcholine group-containing silicone compound is represented by formula (1). (In formula (1), R1 is an alkyl group having 1-18 carbon atoms or a phosphorylcholine group-containing moiety represented by formula (2); R2 is a methyl group or a phosphorylcholine group-containing moiety represented by formula (2); and at least either R1 or R2 is a phosphorylcholine group-containing moiety represented by formula (2). n represents an integer of 20-500, and m represents an integer of 1-70.) (In the formula (2), X is -CH2CH2- or -CH2CH2CH2-. l represents 0 or 1.)

Description

A phosphorylcholine group-containing silicone compound and its manufacturing method, a composition for contact lenses, a polymer, and a contact lens.

[0001] The present invention relates to a phosphorylcholine group-containing silicone compound, a method for producing the same, a contact lens composition, a polymer, and a contact lens.

[0002] Silicone hydrogel contact lenses have high oxygen permeability, resulting in a low risk of eye diseases due to insufficient oxygen supply to the cornea. However, silicone hydrogel contact lenses contain hydrophobic silicone compounds. Therefore, there are concerns that the wettability and lubricity of the lens surface may be insufficient, increasing the risk of eye diseases due to mechanical irritation during blinking. In addition, when wearing contact lenses, the tear film on the contact lens surface becomes thinner and dries out easily, and there are concerns that mechanical irritation will become stronger when dry. For this reason, surface hydrophilization by surface modification methods and surface hydrophilization by mixing hydrophilic polymers into the lens composition before hardening are being investigated.

[0003] For example, Patent Document 1 discloses a silicone hydrogel contact lens produced by random copolymerization of 2-methacryloyloxyethyl phosphorylcholine (hereinafter also referred to as "MPC") and a hydroxyl-containing siloxane monomer 2-hydroxy-3-(tris(trimethylsiloxy)silyl)propyl methacrylate (hereinafter also referred to as SiGMA). When introducing phosphorylcholine groups into this silicone hydrogel lens, if MPC is used in copolymerization, it is desirable to further reduce the phase separation between the highly hydrophilic MPC portion and the hydrophobic silicone portion in the silicone hydrogel skeleton.

[0004] For example, Patent Document 2 discloses a silicone hydrogel contact lens containing a silicone component and a hydrophilic polymer. In this silicone hydrogel contact lens, the hydrophilic polymer has compatibility issues with the silicone component. Therefore, in order to obtain a contact lens without impairing oxygen permeability, it is necessary to use other compatibilizer components or solvents, which imposes certain limitations on the lens composition.

[0005] For example, Patent Document 3 and Patent Document 4 disclose a polysiloxane monomer in which a phosphorylcholine-like group is introduced into a polydimethylsiloxane part of the main chain, and a silicone hydrogel contact lens using the polydimethylsiloxane monomer. The silicone hydrogel contact lens according to this Patent Document 3 has obtained good results in terms of the wettability and oxygen permeability of the lens surface. In addition, the silicone hydrogel contact lens according to Patent Document 4 has also obtained good results in terms of mechanical strength.

[0006] Japanese Patent Application Laid-Open No. 2007-197513, Japanese Patent Application Laid-Open No. 2012-140631, International Publication No. 2019 / 194264, International Publication No. 2020 / 218220

[0007] However, although the conventionally known silicone hydrogel contact lens has good wettability on the lens surface, there is room for improvement in terms of the lubricity of the lens surface and drying due to long-term wearing. That is, it is desirable to be able to maintain a higher degree of lubricity of the lens surface even when drying occurs due to long-term wearing.

[0008] Therefore, an object of the present invention is to provide a phosphorylcholine group-containing silicone compound and a method for producing the same, a composition for contact lenses, a polymer, and a contact lens that can produce a contact lens having good wettability and maintaining the lubricity of the lens surface even when drying occurs due to environmental factors such as long-term wearing, low humidity, strong wind, and long-term viewing of a display.

[0009] As a result of intensive studies, the present inventors have found that a phosphorylcholine group-containing silicone compound represented by the following formula (1) can achieve the above problems, and have completed the present invention.

[0010] That is, the present invention relates to the following phosphorylcholine group-containing silicone compound, composition for contact lenses, polymer, and contact lens.

[0011] [1] A phosphorylcholine group-containing silicone compound represented by formula (I).

[0012] [In formula (1), R １ is an alkyl group having 1 to 18 carbon atoms or a phosphorylcholine group-containing moiety represented by formula (2), and R ２ is a methyl group or a phosphorylcholine group-containing moiety represented by formula (2), and either R １ or R ２ is a phosphorylcholine group-containing moiety represented by formula (2). n represents an integer of 20 to 500, and m represents an integer of 1 to 70. ] [In formula (2), X is -CH ２ CH ２ - or -CH ２ CH ２ CH ２ -. l represents 0 or 1. ]

[0013] [2] A method for producing a phosphorylcholine group-containing silicone compound, comprising a step of subjecting a silicone compound represented by formula (3) and a compound represented by formula (4) to an addition reaction. [In formula (3), R ３ is an alkyl group having 1 to 18 carbon atoms or a hydrogen atom, R ４ is a methyl group or a hydrogen atom, and either R ３ or R ４ is a hydrogen atom. n represents an integer of 20 to 500, and m represents an integer of 1 to 70. ] [In formula (4), Y is CH ２ =CH- or CH ２ =CHCH ２ -. l represents 0 or 1. ]

[0014] [3] A contact lens composition containing the phosphorylcholine group-containing silicone compound represented by the above formula (1). [4] The contact lens composition according to [3], further containing a monomer component and containing 10 to 40 parts by mass of the phosphorylcholine group-containing silicone compound based on 100 parts by mass of the total monomer component. [5] The contact lens composition according to [4], wherein the monomer component contains a silicone-containing monomer and a hydrophilic monomer. [6] A polymer obtained by polymerizing the contact lens composition according to [4] or [5]. [7] A contact lens containing a hydrate of the polymer according to [6].

[0015] According to the present invention, it is possible to provide a phosphorylcholine group-containing silicone compound that has good wettability and maintains the lubricity of the lens surface even when drying occurs due to prolonged wear, as well as a method for producing the same, a contact lens composition, a polymer, and a contact lens.

[0016] One embodiment of the present invention relates to a silicone compound containing a phosphorylcholine group, which is an amphoteric group. More specifically, the phosphorylcholine group-containing silicone compound includes a silicone moiety and further contains an amphoteric phosphorylcholine group within the molecule.

[0017] As described above, since the phosphorylcholine group-containing silicone compound contains a silicone moiety, it has good compatibility with monomers commonly used in silicone hydrogel lens compositions. Furthermore, because the phosphorylcholine moiety, which is an amphoteric group, is present in the side chain of the phosphorylcholine group-containing silicone compound, it can impart high hydrophilicity and lubricity to the contact lens surface. In addition, the phosphorylcholine group-containing silicone compound does not contain polymerizable functional groups. Therefore, when the contact lens polymer containing the phosphorylcholine group-containing silicone compound is hydrated, the phosphorylcholine group is easily oriented onto the contact lens surface. As a result, the hydrophilicity and lubricity derived from the phosphorylcholine group are more readily expressed. In this way, high hydrophilicity and lubricity can be imparted to the contact lens surface, allowing for good wettability while maintaining good lubricity even after prolonged wear.

[0018] Other embodiments of the present invention relate to a method for producing the phosphorylcholine group-containing silicone compound described above, a contact lens composition using the phosphorylcholine group-containing silicone compound, a polymer, and a contact lens.

[0019] Embodiments of the present invention will be described in detail below. However, the present invention is not limited to these embodiments. Furthermore, in this specification, a numerical range represented by "~" means a range that includes the numbers written before and after "~" as the lower and upper limits.

[0020] 1. Phosphorylcholine-containing silicone compounds Phosphorylcholine-containing silicone compounds are represented by formula (1).

[0021] In formula (1), R １ This is an alkyl group having 1 to 18 carbon atoms (R=C ａ H ｂ : indicates a phosphorylcholine group-containing site represented by formula (2) (a = 2 to 18, b = 2a + 1). The alkyl group having 1 to 18 carbon atoms is preferably an alkyl group having 1 to 12 carbon atoms, more preferably an alkyl group having 1 to 6 carbon atoms. Examples of alkyl groups having 1 to 18 carbon atoms include ethyl group, propyl group, butyl group, pentyl group, isopentyl group, hexyl group, isohexyl group, octyl group, etc. ２ R indicates a methyl group or a phosphorylcholine group-containing site represented by formula (2). １ or R ２ Either of these is a phosphorylcholine group-containing site represented by formula (2). n and m are not particularly limited as long as they are within the above range, but n is an integer from 20 to 500, preferably from 30 to 300, more preferably from 40 to 200, and m is an integer from 1 to 70, preferably from 2 to 50, more preferably from 3 to 20.

[0022]

[0023] In equation (2), X is -CH ２ CH ２ - or -CH ２ CH ２ CH ２ It indicates a negative sign. l indicates 0 or 1.

[0024] The number-average molecular weight of the phosphorylcholine group-containing silicone compound is preferably 2,000 to 30,000. The number-average molecular weight can be measured by nuclear magnetic resonance (NMR). If the number-average molecular weight of the phosphorylcholine group-containing silicone compound is 2,000 or more, the mechanical strength of the resulting lens can be further increased. If the number-average molecular weight of the phosphorylcholine group-containing silicone compound is 30,000 or less, the influence on the shape of the lens (e.g., deformation) can be further suppressed.

[0025] 2. Method for synthesizing phosphorylcholine group-containing silicone compounds. Phosphorylcholine group-containing silicone compounds, specifically those represented by formula (1) above, can be synthesized by various methods and are not particularly limited. For example, a phosphorylcholine group-containing silicone compound can be produced by an addition reaction between a silicone compound represented by formula (3) and a compound represented by formula (4).

[0026] 2-1. Regarding the silicone compound represented by formula (3), in formula (3), R ３ R is an alkyl group having 1 to 18 carbon atoms or a hydrogen atom. ４ R is a methyl group or a hydrogen atom, ３ or R ４ One of them is a hydrogen atom. The alkyl group having 1 to 18 carbon atoms is preferably an alkyl group having 1 to 12 carbon atoms, more preferably an alkyl group having 1 to 6 carbon atoms. n is an integer from 20 to 500, and m is an integer from 1 to 70. n and m are not particularly limited as long as they are within the above ranges, but n is an integer from 20 to 500, preferably from 30 to 300, more preferably from 40 to 200, and m is an integer from 1 to 70, preferably from 2 to 50, more preferably from 3 to 20.

[0027] The silicone compound represented by formula (3) can be obtained by reacting the silicone compound represented by formula (5) with octamethylcyclotetrasiloxane and / or 1,3,5,7-tetramethylcyclotetrasiloxane, for example, using an acid catalyst.

[0028]

[0029] In equation (5), R ５ This is an alkyl group having 1 to 18 carbon atoms (R=C ａ H ｂ C1-C18 alkyl groups are C1-C12 alkyl groups, and more preferably C1-C6 alkyl groups.

[0030] Examples of silicone compounds represented by formula (5) include 1,1,3,3-tetramethyldisiloxane and hexamethyldisiloxane. The silicone compound represented by formula (5) may be commercially available or synthesized by known methods. When synthesizing the silicone compound represented by formula (5), it can be synthesized by hydrosilylation, an addition reaction, of 1,1,3,3-tetramethyldisiloxane with various alkenes having 2 to 18 carbon atoms (e.g., ethylene, propylene, butylene, pentylene, heysilene, 2-methylpentylene). If necessary, the catalyst used in the reaction can be removed by adsorption or liquid-liquid extraction, and unreacted components can be removed by reduced pressure.

[0031] Next, as described above, the silicone compound represented by formula (5) is reacted with octamethylcyclotetrasiloxane and / or 1,3,5,7-tetramethylcyclotetrasiloxane using an acid catalyst such as trifluoromethanesulfonic acid to obtain the silicone compound represented by formula (3) (hydrosilyl group-containing silicone intermediate). At this time, no solvent may be used, or a solvent such as chloroform may be used.

[0032] The acid catalyst after the reaction is removed by known methods. For example, it can be removed by washing with water or by adsorption with sodium bicarbonate.

[0033] 2-2. Regarding the compound represented by formula (4), in formula (4), Y is CH ２=CH- or CH ２ =CHCH ２ It indicates a negative sign. l indicates 0 or 1.

[0034] The compound represented by formula (4) is obtained by reacting an alcohol represented by formula (6) with 2-chloro-2-oxo-1,3,2-dioxaphosphorane (COP) in an aprotic solvent such as acetonitrile, and then reacting it with trimethylamine in an aprotic solvent such as acetonitrile. [In equation (6), Y is CH ２ =CH- or CH ２ =CHCH ２ It indicates -. l indicates 0 or 1.

[0035] 2-3. Addition Reaction The silicone compound represented by formula (3) (hydrosilyl group-containing silicone intermediate) and the compound represented by formula (4) (phosphorylcholine group-containing intermediate) are subjected to a hydrosilylation addition reaction. The excess amount of the compound represented by formula (4) is removed with a solvent, and the low-boiling point component is removed by reducing the pressure. This yields the phosphorylcholine group-containing silicone compound represented by formula (1).

[0036] 3. Contact Lens Composition The contact lens composition contains a phosphorylcholine group-containing silicone compound represented by formula (1) as described above. The contact lens composition of this embodiment is preferably a monomer composition for manufacturing contact lenses. The contact lens composition (hereinafter also simply referred to as "composition") contains at least a phosphorylcholine group-containing silicone compound represented by formula (1) and a monomer component.

[0037] 3-1. The content of the phosphorylcholine group-containing silicone compound represented by formula (1) is not particularly limited. For example, the content of the phosphorylcholine group-containing silicone compound represented by formula (1) is, for example, 10 parts by mass or more and 40 parts by mass or more, preferably 10 parts by mass or more and 30 parts by mass or less, and more preferably 15 parts by mass or more and 30 parts by mass or less, per 100 parts by mass of the total monomer components. When the content of the phosphorylcholine group-containing silicone compound represented by formula (1) is 10 parts by mass or more, the surface properties (wettability, lubricity) and lubricity after prolonged wear of the resulting contact lens are improved, and when it is 40 parts by mass or less, the impact on the shape of the resulting contact lens can be reduced.

[0038] 3-2. Monomer Components The above composition preferably contains a silicone-containing monomer and a hydrophilic monomer as monomer components. The above composition has good oxygen permeability due to the inclusion of a silicone-containing monomer. Furthermore, the above composition becomes a hydrated gel due to the inclusion of a hydrophilic monomer, resulting in good wearing comfort and mechanical strength.

[0039] Examples of silicone-containing monomers include 3-[tris(trimethylsiloxy)silyl]propyl methacrylate, 2-hydroxy-3-(tris(trimethylsiloxy)silyl)propyl methacrylate, and polydimethylsiloxane monomer represented by formula (7), with 2-hydroxy-3-(tris(trimethylsiloxy)silyl)propyl methacrylate and polydimethylsiloxane monomer represented by formula (7) being preferred.

[0040] [In equation (7), q represents an integer from 1 to 9.]

[0041] Examples of hydrophilic monomers include hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, N-vinylpyrrolidone, N,N-dimethylacrylamide, N,N-diethylacrylamide, 2-(methacryloyloxyethyl)-2-(trimethylammonioethyl) phosphate, methyl methacrylate, ethylene glycol monovinyl ether, and diethylene glycol monovinyl ether. Preferably, these are hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, N-vinylpyrrolidone, 2-(methacryloyloxyethyl)-2-(trimethylammonioethyl) phosphate, methyl methacrylate, ethylene glycol monovinyl ether, and diethylene glycol monovinyl ether.

[0042] The content ratio of monomer components is not particularly limited, but is, for example, 40 parts by mass or more and 90 parts by mass or less, preferably 50 parts by mass or more and 90 parts by mass or less, and more preferably 60 parts by mass or more and 90 parts by mass or less, based on 100 parts by mass of the total amount of the above composition.

[0043] 3-3. Crosslinking Agents The above composition may also contain crosslinking agents in addition to the above monomers, to the extent that they do not impair the effects of the present invention. Examples of crosslinking agents include ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, ethylene glycol divinyl ether, diethylene glycol divinyl ether, triethylene glycol divinyl ether, and polydimethylsiloxane crosslinking agents represented by formula (8).

[0044] [In equation (8), p represents an integer from 1 to 9.]

[0045] The crosslinking agent content is usually 5 parts by mass or less, preferably 3 parts by mass or less, per 100 parts by mass of the total monomer components.

[0046] 3-4. Solvents The above composition may also contain solvents in addition to the components described above, as long as the effects of the present invention are not impaired. Examples of solvents include alcohols and carboxylic acids. Examples of alcohols include ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, tert-butanol, 1-pentanol, 2-pentanol, tert-amyl alcohol, 1-hexanol, 1-octanol, 1-decanol, 1-dodecanol, ethylene glycol, and propylene glycol. Examples of carboxylic acids include glycolic acid, lactic acid, and acetic acid. The solvent may be any one of these, or a mixture of two or more.

[0047] The solvent content is typically 20 parts by mass or less, preferably 15 parts by mass or less, and more preferably 10 parts by mass or less, per 100 parts by mass of the total monomer components.

[0048] 3-5. Initiator The above composition may further contain a polymerization initiator to the extent that it does not impair the effects of the present invention. When the above composition contains a polymerization initiator, a polymer can be obtained by heating the above composition. The initiator is not particularly limited, but thermal polymerization initiators such as peroxides and azo compounds, and photopolymerization initiators can be used.

[0049] When thermal polymerization is performed, a compound with optimal decomposition characteristics for the desired reaction temperature can be selected and used. Specifically, peroxides or azo compounds with a 10-hour half-life temperature of 40 to 120°C are preferred. Examples of thermal polymerization initiators include 2,2'-azobisisobutyronitrile, dimethyl 2,2-azobis(2-methylpropionate)2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride, 2,2'-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis[2-(2-imidazolin-2-yl)propane]disulfate dihydrate, 2,2'-azobis(2-methylpropionamidine)dihydrochloride, 2,2'-azobis[N-(2-carboxyethyl)-2-methylpropionamidine]dihydrate, 2,2'-azobis[2-(2-imidazolin-2-yl)propane], and 2,2'-azobis(1 Examples of azo polymerization initiators include imino-1-pyrrolidino-2-methylpropane) dihydrochloride, 2,2'-azobis[2-methyl-N-{1,1-bis(hydroxymethyl)-2-hydroxyethyl}propionamide], 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide], and 2,2'-azobis(2-methylpropionamidine) dihydrochloride, as well as peroxide polymerization initiators such as benzoyl peroxide, t-butyl hydroperoxide, cumene hydroperoxide, lauroyl peroxide, t-butyl peroxyhexanoate, and 3,5,5-trimethylhexanoyl peroxide.

[0050] Examples of photopolymerization initiators include carbonyl compounds, sulfur compounds, halogen compounds, and metal salts. Examples of photopolymerization initiators include 1-hydroxycyclohexylphenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide, bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide, 2,4,6-trimethylbenzyldiphenylphosphine oxide, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, benzoin methyl ester, camphorquinone, and ethyl-4-(N,N-dimethylamino)benzoate. Examples of photopolymerization initiators indicated by trade names include Irgacure 819, Irgacure 1700, Irgacure 1800, Irgacure 819, Irgacure 1850, Darocure 1173, and Darocure 2959.

[0051] The initiator content is, for example, 0.1 parts by mass or more and 3 parts by mass or less, preferably 0.1 parts by mass or more and 2 parts by mass or less, and more preferably 0.2 parts by mass or more and 1 part by mass or less, based on 100 parts by mass of the total monomer components.

[0052] 3-6. Preparation Method The method for preparing the above composition is not particularly limited, and for example, it can be produced by mixing each component at a temperature of, for example, 10 to 50°C until homogeneous. The components may be mixed in any order or all at once. If the above composition contains a thermal polymerization initiator, it is preferable to mix it at, for example, 40°C or below so that the polymerization reaction does not start during mixing. If the above composition contains a photopolymerization initiator, it is preferable to mix it while shielding it from light.

[0053] 4. Polymers are obtained by polymerizing the above composition. Polymerization can be carried out by known methods.

[0054] For example, a polymer can be produced by filling a mold with the above composition and carrying out a polymerization reaction. In the case of a composition that does not contain an initiator, a polymerization initiator similar to the initiator is added to the composition in the above-mentioned amount, dissolved, and then filled into the mold. A mold having a hydrophobic surface made of polypropylene or the like may be used as the mold.

[0055] When polymerizing the above composition with a thermal polymerization initiator, it is preferable to react it for at least one hour at a temperature between 45 and 140°C, which is suitable for the contained thermal polymerization initiator. When polymerizing the above composition with a photopolymerization initiator, irradiation with ultraviolet light of a wavelength suitable for the contained photopolymerization initiator at 0.3 mW / cm² is preferable. ２ It is preferable to allow the reaction to proceed at the above illumination level for at least 5 minutes. After polymerization is complete, the mixture is cooled to, for example, 60°C or below, and the produced polymer is removed from the mold.

[0056] The polymerization atmosphere is not particularly limited, but it is preferable to carry out the polymerization in an inert gas atmosphere such as nitrogen or argon in order to improve the polymerization rate. In this case, the inert gas may be passed through the composition, or the area where the composition is filled in the mold may be in an inert gas atmosphere.

[0057] The polymer after the polymerization reaction may be in a mixture state with unreacted monomer components (unreacted material), residues of each component, by-products, and remaining solvent. It is preferable to remove such mixtures using a purifying solvent before hydration (purify the polymer). Examples of purifying solvents include water, methanol, ethanol, 1-propanol, 2-propanol, and mixtures thereof.

[0058] 5. Contact Lenses: The polymer exhibits good surface properties (wettability, lubricity) upon hydration, and can maintain good lubricity even during prolonged wear. Therefore, the polymer can be suitably used in contact lenses, preferably silicone hydrogel contact lenses. In other words, contact lenses can contain the hydrate of the polymer.

[0059] Here, "hydrate" means that it contains water, and refers to a polymer that has absorbed water and exhibits a hydrogel form.

[0060] The hydrate of the above polymer can be obtained, for example, by immersing the purified polymer in physiological saline and hydrating it to a predetermined water content. The physiological saline may be borate-buffered saline, phosphate-buffered saline, etc. The osmotic pressure of the physiological saline is preferably 250 to 400 mOms / kg for hydration. This makes it possible to obtain contact lenses containing the hydrate of the above polymer.

[0061] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0062] 1. Preparation of materials 1-1. Synthesis of phosphorylcholine group-containing intermediate 97.26 g (0.68 mol) of 2-chloro-2-oxo-1,3,2-dioxaphosphoran (COP) was dissolved in 389.03 g of acetonitrile in a 1 L four-necked flask and cooled to below 5°C in an ice bath. 66.38 g (0.65 mol) of ethylene glycol monoallyl ether (manufactured by Tokyo Chemical Industry Co., Ltd.) and 69.07 g (0.68 mol) of triethylamine (manufactured by Kishida Chemical Co., Ltd.) were dissolved in 135.45 g of acetonitrile in a 500 mL beaker. This solution was transferred to a 300 mL dropping funnel and added dropwise to the COP solution over 1 hour. The reaction was then carried out in an ice bath for 4 hours. After filtering off the triethylamine hydrochloride produced by the reaction, 61.46 g (1.04 mol) of trimethylamine was added and the mixture was reacted at 75°C for 8 hours. After cooling, the resulting product was filtered off and washed twice with 140 g of acetone. By removing the solvent under reduced pressure, 104.1 g of the target product was obtained. The obtained target product is a phosphorylcholine group-containing intermediate (where Y in formula (4) is CH). ２ =CHCH ２ (A compound in which l is 1) １ Confirmed by 1H NMR.

[0063] 1-2. Synthesis of Hydrosilyl Group-Containing Silicone Intermediates 1-2-1. Synthesis of Hydrosilyl Group-Containing Silicone Intermediate-1 In a 200 mL light-shielding bottle, 4.69 g of tetramethyldisiloxane and 100 g of octamethylcyclotetrasiloxane were mixed, and then 0.157 g of trifluoromethanesulfonic acid was added. After reacting at 25°C for 6 hours, 20.94 g of sodium sulfate and 0.877 g of sodium bicarbonate were added. After filtration, low-boiling components were removed by reduced pressure to obtain 86.9 g of a clear liquid. The obtained clear liquid was, １ ¹H NMR revealed a hydrosilyl group-containing silicone intermediate having hydrosilyl groups at both ends (R of formula (3)). ３ is a hydrogen atom, R ４ It was confirmed that the compound is a methyl group and n and m together are 55 (hereinafter referred to as "silicone intermediate-1"). １ [H NMR Analysis Values] Peak area value of 2H at the terminal hydrosilyl group at 4.69 ppm (2.00) Peak area value of siloxane-derived peak at 0.07 ppm (296.33)

[0064] 1-2-2. Synthesis of Hydrosilyl Group-Containing Silicone Intermediate-2 In a 200 mL light-shielding bottle, 0.4759 g of tetramethyldisiloxane, 20.00 g of octamethylcyclotetrasiloxane, and 4.06 g of 1,3,5,7-tetramethylcyclotetrasiloxane were mixed, and then 0.0341 g of trifluoromethanesulfonic acid was added. After reacting at 25°C for 6 hours, 4.91 g of sodium sulfate and 0.206 g of sodium bicarbonate were added. After filtration, low-boiling components were removed by reduced pressure to obtain 18.89 g of a clear liquid. The obtained clear liquid was, １ ¹H NMR revealed a hydrosilyl group-containing silicone intermediate having hydrosilyl groups at both ends and in the main chain portion (R of formula (3)). ３ and R ４ It was confirmed that the compound is a hydrogen atom, and that the silicone intermediate-2 has n = 105 and m = 13. １ [H NMR Analysis Values] Peak area value of terminal and principal hydrosilyl groups at 4.68 ppm (24.12) Peak area value of siloxane-derived group at 0.06 ppm (682.18)

[0065] 1-2-3. Synthesis of Hydrosilyl Group-Containing Silicone Intermediate-3 (Synthesis of Dihexyltetramethyldisiloxane) 31.34 g of 1-hexene, 31.37 g of toluene, and 108 μL of 4 wt% platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex-xylene solution were added to a 200 mL four-necked flask and mixed. A 100 mL dropping funnel was loaded with a solution of 19.03 g of tetramethyldisiloxane dissolved in 20.00 g of toluene and attached to the top of a three-necked flask. The liquid in the dropping funnel was added dropwise over 30 minutes while maintaining a temperature below 30°C. After addition, the reaction was carried out for a further 7 hours. The low-boiling components were removed by distillation under reduced pressure. The resulting clear liquid was １ It was confirmed to be dihexyltetramethyldisiloxane by 1H NMR. １ [H NMR Analysis Values] Peak area value of methyl group derived from terminal hexyl group at 0.88 ppm (5.97) Peak area value derived from siloxane at 0.02 ppm (12.50)

[0066] (Synthesis of Hydrosilyl Group-Containing Silicone Intermediate) In a 200 mL light-shielding bottle, 2.94 g of dihexyltetramethyldisiloxane, 50.0 g of octamethylcyclotetrasiloxane, and 10.15 g of 1,3,5,7-tetramethylcyclotetrasiloxane were mixed, and then 0.105 g of trifluoromethanesulfonic acid was added. After reacting at 25°C for 8 hours, 12.65 g of sodium sulfate and 0.55 g of sodium bicarbonate were added. After filtration, low-boiling components were removed by reduced pressure to obtain 49.54 g of a clear liquid. The obtained clear liquid was, １ ¹H NMR revealed a hydrosilyl group-containing silicone intermediate having hexyl groups at both ends and a hydrosilyl group in the main chain (formula (3) R ３ The hexyl group is R ４ It was confirmed that the compound is a hydrogen atom (referred to as silicone intermediate-3). １ [H NMR Analysis Values] Peak area value of the 2H methyl group derived from the terminal hexyl group at 0.87 ppm (6.21) Area value derived from the hydrosilyl group at 4.67 ppm (15.79) Peak area value derived from the siloxane at 0.16 ppm (498.30)

[0067] 2. Synthesis and Measurement of Phosphorylcholine Group-Containing Silicone Compounds [Measurement of Composition Ratio and Number Average Molecular Weight] The composition ratio and number average molecular weight of phosphorylcholine group-containing silicone compounds are as follows: １ The measurement was performed using 1H NMR. The measurement conditions are as follows: １ H NMR measurement method) Measuring device: JNM-AL400 manufactured by JEOL Ltd. Solvent: CDCl ３ (TMS standard)

[0068] [Example 1-1] In a 200 mL four-necked flask, 20.05 g of silicone intermediate-1 and 4.80 g of the phosphorylcholine group-containing intermediate prepared above were dissolved in 74.62 g of 2-propanol, and 170 μL of 4 wt% hexachloroplatinic acid hexahydrate 2-propanol solution was added. The mixture was heated to 75°C using an oil bath and stirred for 6 hours. After cooling to room temperature, the mixture was concentrated and the solvent was removed. To the obtained reaction mixture, 25.0 g of deionized water, 37.5 g of 2-propanol, and 25.0 g of heptane were mixed and stirred. After standing, the mixture was separated into two layers, the lower layer was discarded, and 13.45 g of a transparent gel was obtained by distillation under reduced pressure. The obtained gel was １ ¹H NMR analysis confirmed that the compound is represented by formula (1) (see Table 1 below). １ [H NMR Analysis Values] Peak area values ​​of 2H at the terminal double bond at 5.54 and 6.10 ppm (1.00 + 1.00 = 2.00) Area value of 9H from the choline group at 3.34 ppm (46.89) Peak area value from siloxane at 0.16 ppm (646.15)

[0069] [Example 1-2] In a 200 mL four-necked flask, 7.99 g of silicone intermediate-2 and 9.09 g of the phosphorylcholine group-containing intermediate prepared above were dissolved in 51.26 g of 2-propanol, and 306 μL of 4 wt% hexachloroplatinic acid hexahydrate 2-propanol solution was added. The mixture was heated to 75°C using an oil bath and stirred for 7.5 hours. After cooling to room temperature, the mixture was concentrated and the solvent was removed. To the obtained reaction mixture, 12.61 g of methanol was added and dissolved, and then the mixture was purified using a dialysis membrane (molecular weight cutoff: 10,000). Subsequently, 12.42 g of a transparent gel was obtained by vacuum distillation. The obtained gel was １ ¹H NMR analysis confirmed that the compound is represented by formula (1) (see Table 1 below). １ [H NMR Analysis Values] Area value of 9H derived from choline group at 3.33 ppm (135.18) Peak area value derived from siloxane at 0.08 ppm (681.28)

[0070] [Examples 1-3] 10.00 g of silicone intermediate-3 and 10.21 g of the phosphorylcholine group-containing intermediate prepared above were dissolved in 60.04 g of 2-propanol in a 200 mL four-necked flask, and 341 μL of a 4 wt% hexachloroplatinic acid hexahydrate 2-propanol solution was added. The mixture was heated to 75°C using an oil bath and stirred for 7.5 hours. After cooling to room temperature, the mixture was concentrated and the solvent was removed. 14.83 g of methanol was added to the resulting reaction mixture and dissolved, and then the mixture was purified using a dialysis membrane (molecular weight cutoff: 10,000). Subsequently, 12.86 g of a transparent gel was obtained by vacuum distillation. The obtained gel was １ ¹H NMR analysis confirmed that the compound is represented by formula (1) (see Table 1 below). １ [H NMR Analysis Values] Area value of 9H derived from choline group at 3.34 ppm (94.25) Peak area value derived from siloxane at 0.06 ppm (498.3)

[0071] Table 1 shows the composition ratio and number-average molecular weight Mn of the phosphorylcholine group-containing silicone compounds synthesized in Examples 1-1 to 1-3.

[0072]

[0073] 3. Preparation and evaluation of compositions, polymers, and contact lenses 3-1. Materials The components other than the phosphorylcholine group-containing silicone compound of the present invention used in Example 2 and Comparative Example are shown below.

[0074] (Silicone-containing monomers) SiGMA: 2-hydroxy-3-(tris(trimethylsiloxy)silyl)propyl methacrylate dPDMS: Compound of formula (7) (average molecular weight: 900)

[0075] (Hydrophilic monomers) MPC: 2-(methacryloyloxyethyl)-2-(trimethylammonioethyl)phosphate NVP: N-vinylpyrrolidone HBMA: 2-hydroxybutyl methacrylate

[0076] (Crosslinking agents) TEGDMA: Tetraethylene glycol dimethacrylate TEGDVE: Triethylene glycol divinyl ether

[0077] (Polymerization initiator) AIBN: 2,2'-azobis(isobutyronitrile) (10-hour half-life temperature 65°C)

[0078] (Solvents) HexOH: 1-Hexanol EtOH: Ethanol

[0079] (Comparative compound) Compound of formula (9): Phosphorylcholine group-containing polysiloxane monomer (average molecular weight Mn = 7,600) PVP K30: (Polyvinylpyrrolidone K30, Fujifilm Wako Pure Chemical Corporation)

[0080] [In equation (9), a represents 74 and b represents 5.]

[0081] 3-2. Evaluation Method [Uniformity of Composition] The uniformity of the composition before polymerization was visually confirmed in a transparent glass vial. Good: No insoluble components or scattering of the solution were observed, and the solution was uniform. Poor: Insoluble components or scattering of the solution were observed.

[0082] [Wettability] The wettability of contact lenses was evaluated by gently removing the contact lens from physiological saline solution and measuring the time it took for the water film on the surface to break (Water film Break-Up Time: WBUT), according to the following criteria. A result of A or B was considered good. A: 10 seconds or more B: 5 to 9 seconds C: 0 to 4 seconds

[0083] [Initial Lubricity] The initial lubricity of contact lenses was evaluated by rubbing the contact lens between the thumb and index finger and scoring it on an 18-point scale from 1 to 10 in 0.5 increments, according to the following criteria. As an index for scoring, polymacon contact lenses were given 2 points, and omafilcon A contact lenses were given 8 points. An evaluation result of A or B was judged to be good. A: 8-10 points B: 5-7.5 points C: 1-4.5 points

[0084] [Lubricity in Dry Condition] The lubricity of contact lenses in dry condition was evaluated by rubbing a contact lens, with its surface moisture removed using non-woven paper, between the thumb and index finger. The ease of rubbing was scored on an 18-point scale from 1 to 10 in 0.5 increments, according to the following criteria. As an index for scoring, polymacon contact lenses were assigned 2 points, and omafilcon A contact lenses were assigned 8 points. An evaluation result of A or B was considered good. A: 8-10 points B: 5-7.5 points C: 1-4.5 points

[0085] 3-3. Preparation of Composition, Polymer and Contact Lens [Example 2-1] (Preparation of Composition) 1.28 g (25.6% by mass) of mPDMS, 1.28 g (25.6% by mass) of SiGMA, 0.96 g (19.2% by mass) of MPC, 0.61 g (12.2% by mass) of NVP, 0.87 g (17.4% by mass) of HBMA, 0.06 g (1.3 parts by mass) of TEGDMA, 0.06 g (1.3 parts by mass) of TEGDVE, 1.00 g (20 parts by mass) of HexOH, and 1.26 g (25.6 parts by mass) of the compound from Example 1-1 were mixed in a container and stirred at room temperature until the compound from Example 1-1 and MPC dissolved. Furthermore, 0.03 g (0.5 parts by mass) of AIBN was added to the container and stirred at room temperature until homogeneous to obtain the composition. Note that the mass percentage in parentheses represents the mass percentage of each monomer when the total amount of monomers is set to 100 mass%, and the parts by mass in parentheses represents the parts by mass of each component when the total amount of monomers is set to 100 parts by mass.

[0086] (Preparation of Polymers) The composition was filled into a lens mold. The lens mold filled with the composition was placed in an oven, and the oven was purged with nitrogen. The oven was then heated to 80°C and maintained at 80°C for 12 hours to polymerize the composition and obtain polymers. Each polymer was removed from the lens mold to obtain polymers.

[0087] (Preparation of Contact Lenses) The polymer was purified by immersing it in 100 mL of deionized water for 4 hours to remove unreacted substances. The purified polymer was then immersed in physiological saline solution as described in ISO-18369-3 to swell (hydrate) and contact lenses were prepared, and each evaluation was performed. The mixing ratio of each component in the composition, polymerization conditions, and each evaluation result are shown in Table 2.

[0088] [Examples 2-2 to 2-6] Contact lenses for each example were prepared in the same manner as in Example 2-1, except that the mixing ratios of each component in the composition were as shown in Table 2. The contact lenses for each example were also evaluated in the same manner as in Example 2-1. The results are shown in Table 2.

[0089] [Comparative Example 1] (Preparation of Composition) 1.28 g (25.6% by mass) of mPDMS, 1.28 g (25.6% by mass) of SiGMA, 0.96 g (19.2% by mass) of MPC, 0.61 g (12.2% by mass) of NVP, 0.87 g (17.4% by mass) of HBMA, 0.06 g (1.3 parts by mass) of TEGDMA, 0.06 g (1.3 parts by mass) of TEGDVE, and 1.00 g (20 parts by mass) of HexOH were mixed in a container and stirred at room temperature until the MPC dissolved. Furthermore, 0.03 g (0.5 parts by mass) of AIBN was added to the container and stirred at room temperature until homogeneous to obtain the composition.

[0090] (Preparation of Polymer) The composition was filled into a lens mold. The lens mold filled with the composition was placed in an oven, and the oven was purged with nitrogen. The oven was then heated to 80°C and maintained at 80°C for 12 hours to polymerize the composition and obtain a polymer.

[0091] (Preparation of Contact Lenses) Each polymer was removed from a lens mold to obtain the polymer. The polymer was purified by immersing it in 100 mL of deionized water for 4 hours to remove unreacted substances, etc. The purified polymer was immersed in physiological saline solution as described in ISO-18369-3 to swell (hydrate) and contact lenses were prepared, and each evaluation was performed. The mixing ratio of each component in the composition, polymerization conditions, and each evaluation result are shown in Table 3.

[0092] [Comparative Example 2] Contact lenses were prepared in the same manner as in Comparative Example 1, except that the mixing ratios of each component in the composition were as shown in Table 3. The contact lenses of Comparative Example 2 were also evaluated in the same manner as in Comparative Example 1. The results are shown in Table 3.

[0093] [Comparative Example 3] 1.02 g (20.3% by mass) of mPDMS, 1.52 g (30.4% by mass) of SiGMA, 1.78 g (35.5% by mass) of NVP, 0.69 g (13.8% by mass) of HBMA, 0.08 g (1.5 parts by mass) of TEGDMA, 1.00 g (20 parts by mass) of EtOH, and 1.02 g (20.3 parts by mass) of PVP K30 were mixed in a container and stirred at room temperature. However, insoluble components were found in the resulting composition, making it impossible to prepare contact lenses, and other evaluations could not be performed.

[0094]

[0095]

[0096] As shown in Table 2, the contact lenses of Examples 2-1 to 2-6 all exhibited high initial wettability, lubricity, and dry lubricity. In contrast, as shown in Table 3, the contact lens of Comparative Example 1 had poorer initial wettability and inferior dry lubricity compared to the contact lenses of each example. The contact lens of Comparative Example 2 also had inferior dry lubricity compared to the contact lenses of each example.

[0097] From these findings, it can be seen that contact lenses obtained from a composition containing a phosphorylcholine group-containing silicone compound represented by formula (1) have good wettability, high lubricity both initially and during drying, and can maintain good lubricity even after drying.

[0098] This application is a priority application claiming under Japanese Patent Application No. 2024-229085 filed on 25 December 2024, and the contents of the specification and claims of said application are incorporated herein by reference.

[0099] The phosphorylcholine group-containing silicone compound of the present invention enables the manufacture of contact lenses that have good wettability while maintaining lubricity of the lens surface even when drying occurs due to prolonged wear.

Claims

1. A phosphorylcholine group-containing silicone compound represented by formula (1). [In formula (1), R １ is an alkyl group having 1 to 18 carbon atoms or a phosphorylcholine group-containing site represented by formula (2), and R ２ is a methyl group or a phosphorylcholine group-containing site represented by formula (2), and at least one of R １ or R ２ is a phosphorylcholine group-containing site represented by formula (2). n represents an integer of 20 to 500, and m represents an integer of 1 to 70. ] [In formula (2), X is -CH ２ CH ２ - or -CH ２ CH ２ CH ２ -. l represents 0 or 1. ] 2. A method for producing a phosphorylcholine group-containing silicone compound, comprising the step of performing an addition reaction between a silicone compound represented by formula (3) and a compound represented by formula (4). [In formula (3), R ３ R is an alkyl group having 1 to 18 carbon atoms or a hydrogen atom. ４ R is a methyl group or a hydrogen atom, ３ or R ４ One of them is a hydrogen atom. n is an integer between 20 and 500, and m is an integer between 1 and 70. [In equation (4), Y is CH ２ =CH- or CH ２ =CHCH ２ It indicates -. l indicates 0 or 1.

3. A contact lens composition comprising the phosphorylcholine group-containing silicone compound described in claim 1.

4. The contact lens composition according to claim 3, further comprising monomer components, wherein the phosphorylcholine group-containing silicone compound is present in an amount of 10 to 40 parts by mass per 100 parts by mass of the total monomer components.

5. The contact lens composition according to claim 4, wherein the monomer component comprises a silicone-containing monomer and a hydrophilic monomer.

6. A polymer obtained by polymerizing the contact lens composition according to claim 4 or 5.

7. A contact lens comprising the polymer hydrate described in claim 6.

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