Phosphorylcholine group-containing polysiloxane monomer

Abstract

A phosphorylcholine group-containing polysiloxane monomer according to the present invention is represented by formula (1). In the formula, a represents an integer of 20 to 500. b represents an integer of 1 to 70. C represents an integer of 1 to 70. d represents 0 or 1. p and q each represent 0 or 1. X represents -CH2- or -CH2CH2-. R represents an alkyl group having 2-18 carbon atoms. It is possible to provide a phosphorylcholine group-containing polysiloxane monomer from which a polymer exhibiting surface hydrophilicity and sufficient stability can be provided for an ophthalmic device when said monomer is polymerized with a polymerizable monomer such as methacrylic acid or a hydrophilic monomer other than the methacrylic acid.

Description

[Technical field]

[0001] The present invention relates to a phosphorylcholine group-containing polysiloxane monomer which can be copolymerized with a hydrophilic monomer or the like to produce ophthalmic devices such as contact lenses, intraocular lenses, and artificial corneas, and a method for producing the same. [Background technology]

[0002] Silicone hydrogels are materials that are widely used in ophthalmic lenses such as contact lenses because they have high oxygen permeability and therefore place less strain on the eyes. On the other hand, silicone hydrogels tend to lack wettability and lubricity due to the inclusion of water-repellent silicone. Therefore, surface hydrophilization by a surface modification method or by mixing a hydrophilic monomer into the lens composition before curing has been investigated.

[0003] Phosphorylcholine groups are known to have excellent properties, such as biocompatibility and extremely high hydrophilicity. Therefore, a method of improving the hydrophilicity of the lens surface using a phosphorylcholine group-containing methacrylic ester monomer (MPC) has been proposed. However, since phosphorylcholine group-containing monomers have high hydrophilicity, they are poorly compatible with hydrophobic silicone. Therefore, Patent Documents 1 to 4 disclose monomer compositions containing a silicone monomer having a hydroxyl group and MPC, and it is becoming possible to obtain silicone hydrogel lenses with high surface hydrophilicity. Furthermore, the use of methacrylic acid has been considered as a method to improve the hydrophilicity of the lens surface. Methacrylic acid has a higher hydrophilicity than general hydrophilic monomers, so its incorporation into the lens is expected to further improve hydrophilicity. However, methacrylic acid is incompatible with the silicone portion of the lens, and there have been stability issues. Therefore, it was necessary to consider the use of methacrylic acid. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent Publication No. 2007-009060 [Patent Document 2] JP 2007-197513 A [Patent Document 3] Patent Publication No. 2014-089477 [Patent Document 4] International Publication No. 2010 / 104000 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a phosphorylcholine group-containing polysiloxane monomer which, when copolymerized with methacrylic acid or a hydrophilic monomer other than methacrylic acid, can give a polymer exhibiting surface hydrophilicity and sufficient stability for an ophthalmic device. [Means for solving the problem]

[0006] As a result of extensive investigations, the present inventors have confirmed that the phosphorylcholine group-containing polysiloxane monomer represented by formula (1) can solve the above problems, and have thus completed the present invention.

[0007] [ka]

[0008] (In the formula, a represents an integer of 20 to 500; b represents an integer of 1 to 70; c represents an integer of 1 to 70; d represents 0 or 1; p and q each represent 0 or 1; X represents -CH2- or -CH2CH2-; R represents a group having 2 to 70 carbon atoms; 8 represents an alkyl group represented by the formula:

[0009] That is, the present invention is as follows. [1] A phosphorylcholine group-containing polysiloxane monomer represented by formula (1): [ka] (In the formula, a represents an integer of 20 to 500; b represents an integer of 1 to 70; c represents an integer of 1 to 70; d represents 0 or 1; p and q each represent 0 or 1; X represents -CH2- or -CH2CH2-; R represents a group having 2 to 70 carbon atoms; 8 represents an alkyl group represented by the formula: [2] A method for producing a phosphorylcholine group-containing polysiloxane monomer represented by formula (1), comprising a step of addition reacting a hydrosilyl group-containing, both-terminated methacrylic silicone represented by formula (4) with a phosphorylcholine compound represented by formula (6). [ka] (In the formula, a represents an integer of 20 to 500; b represents an integer of 1 to 70; c represents an integer of 1 to 70; d represents 0 or 1; p and q each represent 0 or 1; X represents -CH2- or -CH2CH2-; R represents a group having 2 to 70 carbon atoms; 8 represents an alkyl group represented by the formula: [ka] (In the formula, a represents an integer of 20 to 500; b represents an integer of 1 to 70; c represents an integer of 1 to 70; p and q each represent 0 or 1; R represents a group having 2 to 500 carbon atoms; 8 represents an alkyl group represented by the formula: [ka] (In the formula, d represents 0 or 1. Z represents CH2=CHCH2- or CH2=CH-.) [3] A monomer composition comprising 10% by mass to 45% by mass of a phosphorylcholine group-containing polysiloxane monomer represented by formula (1), 10% by mass to 40% by mass of a hydroxyl group-containing siloxanyl group-containing monomer represented by formula (8) or formula (9), 0.1% by mass to 5% by mass of methacrylic acid, and 30% by mass to 70% by mass of a hydrophilic monomer other than methacrylic acid. [ka] (In the formula, a represents an integer of 20 to 500; b represents an integer of 1 to 70; c represents an integer of 1 to 70; d represents 0 or 1; p and q each represent 0 or 1; X represents -CH2- or -CH2CH2-; R represents a group having 2 to 70 carbon atoms; 8 represents an alkyl group represented by the formula: [ka] [ka] [4] A polymer obtained by polymerizing the monomer composition described in [3] above. Effect of the Invention

[0010] The phosphorylcholine group-containing polysiloxane monomer of the present invention has high hydrophilicity due to the phosphorylcholine group, and therefore when copolymerized with methacrylic acid or a hydrophilic monomer other than methacrylic acid, it satisfies surface hydrophilicity and is useful as a polysiloxane monomer used as a raw material for ophthalmic devices.Furthermore, by having an alkyl substituent structure in the side chain, it is a stable monomer with good compatibility with methacrylic acid. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present invention relates to a polysiloxane monomer containing a phosphorylcholine group, which is a zwitterionic group. More specifically, the polysiloxane monomer containing a phosphorylcholine group of the present invention relates to a polymerizable silicone compound that contains a silicone moiety and further contains a zwitterionic phosphorylcholine group, an alkyl substituent, and two vinyl terminal groups in the molecule. The vinyl group of the phosphorylcholine group-containing polysiloxane monomer of the present invention is adjacent to a carbonyl group, and therefore has good copolymerizability with monomers commonly used in ophthalmic devices, such as methacrylic ester monomers and acrylamide monomers. Since the phosphorylcholine group-containing polysiloxane monomer of the present invention has a phosphorylcholine moiety, which is an amphoteric ionic group, in its side chain, it has high compatibility with hydrophilic monomers, and a transparent lens can be obtained by polymerization with the monomer. The side chains of the phosphorylcholine group-containing polysiloxane monomer of the present invention contain alkyl substituents, providing stability to methacrylic acid. In addition, the ophthalmic device in the present invention includes, but is not limited to, a contact lens, a soft contact lens, a hard contact lens, an intraocular lens, and an artificial cornea.

[0012] (Phosphorylcholine Group-Containing Polysiloxane Monomer of the Present Invention) The phosphorylcholine group-containing polysiloxane monomer of the present invention is represented by the following formula (1).

[0013] [ka] (In the formula, a represents an integer of 20 to 500. b represents an integer of 1 to 70. c represents an integer of 1 to 70. d represents 0 or 1. p and q each represent 0 or 1. X represents -CH2- or -CH2CH2-. R represents an alkyl group having 2 to 18 carbon atoms.) Each of a, b, and c is not particularly limited as long as it is within the above-mentioned range, but a is 20 to 500, preferably 20 to 300, more preferably 20 to 200, even more preferably 25 to 170, and particularly preferably 30 to 120; b is 1 to 70, preferably 1 to 40, more preferably 1 to 20, even more preferably 1 to 10, and particularly preferably 1 to 3; and c is 1 to 70, preferably 1 to 40, more preferably 1 to 20, even more preferably 1 to 10, and particularly preferably 1 to 5. R represents an alkyl group having 2 to 18 carbon atoms, including linear and branched structures (R=C n H m: n=2 to 18, m=2n+1), preferably having 3 to 12 carbon atoms, and more preferably having 3 to 8 carbon atoms. For example, it represents a propyl group, a butyl group, a pentyl group, an isopentyl group, a hexyl group, an isohexyl group, an octyl group, etc. The number average molecular weight of the phosphorylcholine group-containing polysiloxane monomer of the present invention is preferably 2000 to 50000. The number average molecular weight can be measured by gel permeation chromatography (GPC).

[0014] (Method of Synthesizing Phosphorylcholine Group-Containing Polysiloxane Monomer of the Present Invention) The phosphorylcholine group-containing polysiloxane monomer of the present invention can be synthesized by various methods, and is not particularly limited. For example, the following methods can be mentioned. The silicone intermediate represented by formula (2) used in the synthesis of the phosphorylcholine group-containing polysiloxane monomer of the present invention can be synthesized by a known method. A siloxane having hydroxyl groups at both ends represented by the following formula (2) {for example, SIB1138.0 (p=q=1, n=0 in formula (2)) and SIB1145.0 (p=q=n=0) from Gelest Co., Ltd., a disiloxane having hydroxyl groups at both ends, a silicone having hydroxyl groups at both ends, such as FM-4411 (p=q=1, n=9) from JNC Co., Ltd., and methacrylic acid chloride are reacted in the presence of a dehydrochlorinating agent to synthesize a compound having methacrylic groups at both ends represented by formula (3). An organic amine can be used as the dehydrochlorinating agent. Preferably, a trialkylamine such as triethylamine, a dialkylamine such as diisopropylamine, or an organic amine such as diazabicycloundecene is used. An aprotic solvent can be used during the reaction. Tetrahydrofuran is preferred in terms of solubility.

[0015] [ka] In the formula, p and q each represent 0 or 1. n represents an integer of 0 to 10.

[0016] [ka] In the formula, p and q each represent 0 or 1. n represents an integer of 0 to 10.

[0017] The compound represented by formula (3) can be purchased, for example, from JNC Corporation FM-7711 (p=q=0, n=9), Gelest Corporation DMS-R11 (p=q=0, n=9), Shin-Etsu Chemical Co., Ltd. X22-164AS (p=q=0, n=9), etc.

[0018] The alkyl group-containing cyclic silicone represented by formula (7) used in the synthesis of the phosphorylcholine group-containing polysiloxane monomer of the present invention can be synthesized by a known method. In formula (7), R is an alkyl group having 2 to 18 carbon atoms, and includes linear and branched structures. (R=C n H m (n=2 to 18, m=2n+1) Examples of R include an ethyl group, a propyl group, a butyl group, a pentyl group, an isopentyl group, a hexyl group, an isohexyl group, and an octyl group. The alkyl group-containing cyclic silicone represented by formula (7) is synthesized by carrying out a hydrosilylation reaction, which is an addition reaction between 1,3,5,7-tetramethylcyclotetrasiloxane and various alkenes having 2 to 18 carbon atoms (e.g., ethylene, propylene, butylene, pentylene, hexylene, 2-methylpentylene). If necessary, it is possible to remove the catalyst used in the reaction by adsorption treatment or separation operation, and to remove unreacted components by reducing the pressure. [ka] Next, the compound having methacryl groups at both ends represented by formula (3) is reacted with octamethylcyclotetrasiloxane, 1,3,5,7-tetramethylcyclotetrasiloxane, and alkyl group-containing cyclic silicone represented by formula (7) using an acid catalyst such as trifluoromethanesulfonic acid to obtain a hydrosilyl group-containing silicone intermediate (hydrosilyl group-containing methacryl silicone at both ends) represented by formula (4). At this time, no solvent may be used, or a solvent such as chloroform may be used.

[0019] [ka] (In the formula, a represents an integer of 20 to 500, b represents an integer of 1 to 70, c represents an integer of 1 to 70, p and q each represent 0 or 1, and R represents an alkyl group having 2 to 18 carbon atoms.) Each of a, b, and c is not particularly limited as long as it is within the above-mentioned range, but a is 20 to 500, preferably 20 to 300, more preferably 20 to 200, even more preferably 25 to 170, and particularly preferably 30 to 120; b is 1 to 70, preferably 1 to 40, more preferably 1 to 20, even more preferably 1 to 10, and particularly preferably 1 to 3; and c is 1 to 70, preferably 1 to 40, more preferably 1 to 20, even more preferably 1 to 10, and particularly preferably 1 to 5.

[0020] After the reaction, the acid catalyst can be removed by a known method, for example, by washing with water or by adsorption with sodium hydrogen carbonate or the like.

[0021] Furthermore, the hydrosilyl group-containing methacrylsilicone at both ends represented by formula (4) is subjected to a hydrosilylation reaction, which is an addition reaction, with the phosphorylcholine compound represented by formula (6). The excess compound of formula (6) is then removed with a solvent or the like, and the low boiling point components are then removed under reduced pressure to obtain the phosphorylcholine group-containing polysiloxane monomer of formula (1). The compound of formula (6) can be obtained by reacting the alcohol of formula (5) with 2-chloro-2-oxo-1,3,2-dioxaphospholane (COP) in an aprotic solvent such as acetonitrile, and then reacting the resulting mixture with trimethylamine in an aprotic solvent such as acetonitrile. [ka] In the formula, d represents 0 or 1. Z represents CH2=CHCH2- or CH2=CH-.

[0022] [ka] In the formula, d represents 0 or 1. Z represents CH2=CHCH2- or CH2=CH-.

[0023] (Monomer composition of the present invention) The monomer composition of the present invention contains 10% by mass to 45% by mass of a phosphorylcholine group-containing polysiloxane monomer represented by formula (1), 10% by mass to 40% by mass of a hydroxyl group-containing siloxanyl group-containing monomer represented by formula (8) or formula (9), 0.1% by mass to 5% by mass of methacrylic acid, and 30% by mass to 70% by mass of a hydrophilic monomer other than methacrylic acid. The phosphorylcholine group-containing polysiloxane monomer represented by formula (1) contained in the monomer composition of the present invention can be polymerized with a hydrophilic monomer or the like using a catalyst or initiator known to those skilled in the art. In the monomer composition of the present invention, the content of the phosphorylcholine group-containing polysiloxane monomer represented by formula (1) of the present invention is 10% by mass to 45% by mass, preferably 15% by mass to 35% by mass, based on the total amount of the composition. If it is less than 10% by mass, the stability of the polymer decreases, and if it exceeds 45% by mass, the surface hydrophilicity of the polymer decreases.

[0024] The monomer composition of the present invention contains a hydroxyl group-containing siloxanyl group-containing monomer represented by formula (8) or formula (9). These hydroxyl group-containing siloxanyl group-containing monomers can be suitably used as raw materials for ophthalmic devices. [ka] [ka]

[0025] The content of the hydroxyl group-containing siloxanyl group-containing monomer represented by formula (8) or formula (9) is 10% by mass to 40% by mass, preferably 20% by mass to 35% by mass, based on the total amount of the composition. If it is less than 10% by mass, the transparency of the polymer decreases, and if it exceeds 40% by mass, the hydrophilicity of the polymer surface decreases.

[0026] The monomer composition of the present invention contains methacrylic acid. By containing methacrylic acid, the hydrophilicity of the ophthalmic device formed from the composition is more likely to be improved. The content of methacrylic acid is 0.1% by mass to 5% by mass, preferably 0.2% by mass to 2% by mass, based on the total amount of the composition. If the content is less than 0.1% by mass, the hydrophilicity of the ophthalmic device is not sufficiently improved, and if the content exceeds 5% by mass, the stability of the polymer decreases.

[0027] The monomer composition of the present invention contains a hydrophilic monomer other than methacrylic acid, which is preferably selected from the group consisting of 2-hydroxyethyl methacrylate, N-vinylpyrrolidone, N,N-dimethylacrylamide, 2-(methacryloyloxyethyl)-2-(trimethylammonioethyl)phosphate, methyl methacrylate, hydroxypropyl methacrylate, hydroxybutyl methacrylate, and mixtures thereof. The content of the hydrophilic monomer other than methacrylic acid is 30% by mass to 70% by mass, preferably 40% by mass to 60% by mass, based on the total amount of the composition. If it is less than 30% by mass, the hydrophilicity of the resulting ophthalmic device is not sufficiently improved, and if it exceeds 70% by mass, the transparency of the polymer decreases.

[0028] (Other Monomers) In addition to the above-mentioned essential monomers, the monomer composition of the present invention can contain other monomers that can be copolymerized with the phosphorylcholine group-containing polysiloxane monomer represented by formula (1) of the present invention and can preferably be used as raw materials for ophthalmic devices.The other monomers may be added as crosslinking agents within a range that does not impair the effects of the present invention.For example, tetraethylene glycol dimethacrylate, triethylene glycol divinyl ether, etc. can be mentioned. The content of the crosslinking agent is usually 10 parts by mass or less, and preferably 5 parts by mass or less, based on 100 parts by mass of the total monomer composition of the present invention.

[0029] (Polymer of the Invention) The polymer of the present invention can be obtained by polymerizing the monomer composition of the present invention. The polymerization can be carried out by a known method by appropriately adding a thermal polymerization initiator, typically a peroxide or an azo compound, or a photopolymerization initiator. When thermal polymerization is performed, a compound having optimal decomposition characteristics for the desired reaction temperature can be selected and used. That is, a peroxide or an azo compound having a 10-hour half-life temperature of 40 to 120° C. is suitable. An example of an azo compound is AIBN. Examples of the photopolymerization initiator include carbonyl compounds, sulfur compounds, halogen compounds, and metal salts. These polymerization initiators may be used alone or in combination, and are preferably used in an amount of 0.2 to 2 parts by mass per 100 parts by mass of the monomer composition of the present invention.

[0030] The polymer of the present invention has excellent surface hydrophilicity and stability, and therefore can be suitably used for ophthalmic devices such as contact lenses, soft contact lenses, hard contact lenses, intraocular lenses, and artificial corneas. EXAMPLES

[0031] 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.

[0032] [Synthesis Example 1] Synthesis of alkyl group-containing cyclic silicone represented by formula (7) (R: hexyl) In a 250mL four-neck flask, 8.75g (104mmol) of 1-hexene (Tokyo Chemical Industry Co., Ltd.) was dissolved in 8.75g of toluene of the same weight, and 100μL of platinum (0)-1,3-divinyltetramethyldisiloxane complex (Aldrich Co., Ltd.) was added. After heating to 25℃, a solution of 5.0g (20.8mmol) of 1,3,5,7-tetramethylcyclotetrasiloxane (Tokyo Chemical Industry Co., Ltd.) dissolved in an equal weight of toluene was added dropwise over 30 minutes. After the dropwise addition, the reaction was carried out at 25℃ for 1 hour, and 13.74g of heptane and 0.5g of activated carbon were added and stirred for another 1 hour. Then, filtration was carried out to remove the activated carbon, and the solvent was removed under reduced pressure to obtain 11.37g. It was confirmed by 1H NMR that it was the compound of formula (7) (R: hexyl).

[0033] [Synthesis Example 2] Synthesis of phosphorylcholine compound represented by formula (6) In a 1L four-neck flask, 97.26g (0.68 mol) of 2-chloro-2-oxo-1,3,2-dioxaphospholane (COP) was dissolved in 389.03g of acetonitrile and cooled to 5°C or less in an ice bath. In a 500mL beaker, 66.38g (0.65 mol) of ethylene glycol monoallyl ether (Tokyo Chemical Industry Co., Ltd.) and 69.07g (0.68 mol) of triethylamine (Kishida Chemical Co., Ltd.) were dissolved in 135.45g of acetonitrile, transferred to a 300mL dropping funnel, and dropped into the COP solution over 1 hour. The reaction was further carried out for 4 hours in an ice bath. After filtering out the triethylamine hydrochloride produced by the reaction, 61.46g (1.04 mol) of trimethylamine was charged and reacted at 75°C for 8 hours. After cooling, the target product produced was filtered out and washed twice with 140g of acetone. The solvent was removed under reduced pressure to obtain 104.1 g, which was confirmed by 1H NMR to be the compound of formula (6) (d is 1 and Z is CH2=CHCH2-).

[0034] [Synthesis Example 3] Synthesis of hydrosilyl-containing methacrylsilicone at both ends represented by formula (4) In a 500 mL light-shielding bottle, 10.27 g of X22-164AS (manufactured by Shin-Etsu Chemical Co., Ltd., both-terminal methacryloyloxypropyl polydimethylsiloxane (molecular weight ≒ 1,000)), 43.7 g of octamethylcyclotetrasiloxane, 2.25 g of 1,3,5,7-tetramethylcyclotetrasiloxane, and 5.40 g of alkyl group-containing cyclic silicone (R: hexyl) represented by formula (7) were mixed, and 0.09 g of trifluoromethanesulfonic acid was further added. After reacting for 18 hours at 25 ° C, 0.52 g of sodium bicarbonate was added to neutralize and stop the reaction. Then, 6.16 g of sodium sulfate was added and dehydrated for 30 minutes. The sodium bicarbonate and sodium sulfate were removed by filtration to obtain 58.70 g of a transparent liquid. It was confirmed by 1H NMR that it was a hydrosilyl group-containing both-terminal methacrylic silicone (referred to as silicone intermediate 1) of formula (4).

[0035] 1H NMR analysis Peak area values ​​of 2H of terminal double bonds at 5.54 and 6.10 ppm (1.00 + 1.01 = 2.01) Area value of 1H derived from hydrosilyl group at 4.68 ppm (3.49) Area value of 8H from hexyl group at 1.31 ppm (30.8) Peak area value (428.13) derived from siloxane at 0.16 ppm From the above, it was calculated that in the structure of the formula (4), a ≈ 71, b = 3, c = 4, p = 0, and q = 0, and the number average molecular weight Mn ≈ 4500. The number average molecular weight was measured using gel permeation chromatography (GPC) and calculated using PMMA (polymethyl methacrylate) as the standard.

[0036] Analysis conditions for Example 1 The analytical conditions in Example 1 are shown below. 1H NMR measurement method Measuring device: JNM-AL400 manufactured by JEOL Ltd. Solvent: CDCl3 (based on the CDCl3 peak at 7.26 ppm)

[0037] Components used in Example 2 and Comparative Example The components other than the polysiloxane monomer of the present invention used in Example 2 and the Comparative Example are shown below. Comparative compound of formula (1) FM-7721: JNC Corporation, methacryloyloxy-terminated polydimethylsiloxane (molecular weight ≒ 5,000) Hydroxyl group-containing siloxanyl group-containing monomer SiGMA: 2-hydroxy-3-(tris(trimethylsiloxy)silyl)propyl methacrylate ETS: 4-(2-hydroxyethyl) = 1-[3-tris(trimethylsiloxy)silylpropyl] = 2-methylidenesuccinate *MMA: Methacrylic acid Hydrophilic monomers DMAA: N,N-Dimethylacrylamide HBMA: Hydroxybutyl methacrylate (mixture of 2-hydroxypropyl ester and 2-hydroxy-1-methylethyl ester, manufactured by Nippon Shokubai Co., Ltd.) NVP: N-vinylpyrrolidone MPC: 2-(methacryloyloxyethyl)-2-(trimethylammonioethyl) phosphate Other monomers TEGDMA: Tetraethylene glycol dimethacrylate Solvent HexOH: Hexanol Initiator (polymerization initiator) AIBN: 2,2'-azobis(isobutyronitrile) (10-hour half-life temperature 65°C)

[0038] The evaluation methods in Example 2 are as follows. The film samples produced in each Example were evaluated by applying the contact lens evaluation methods shown below.

[0039] (Surface hydrophilicity (WBUT) of contact lens (film sample)) The surface hydrophilicity of the film sample was evaluated by WBUT (water film break up time). In detail, the film sample was immersed in ISO physiological saline overnight, and the outer periphery was pinched with tweezers and pulled out from the water surface. The time from when it was pulled out from the water surface until the water film on the film sample surface broke (water film retention time) was measured. The state of the water film breaking was judged by visual inspection. This measurement was carried out three times, and the average value was calculated. If it was 15 seconds or more, the surface hydrophilicity was judged to be good.

[0040] (Water content of contact lens (film sample)) The moisture content was measured according to the method described in ISO-18369-4.

[0041] (Stability of contact lenses (film-like samples)) Film samples immersed in physiological saline solution as described in ISO-18369-3 were stored in a constant temperature bath at 60°C, and the moisture content was measured after one month (referred to as "moisture content after treatment" in the table) and evaluated by comparing with the initial value. When the moisture content changed by ±1% or less, the stability was deemed to be sufficiently good (evaluation A), and when it was between ±1% and ±2%, the stability was deemed to be good (evaluation B).

[0042] [Example 1-1] In a 100mL three-neck flask, 5.00g of silicone intermediate 1 (hydrosilyl group-containing methacrylic silicone at both ends represented by formula (4)) and 1.218g of phosphorylcholine compound represented by formula (6) were dissolved in 7.699g of 2-propanol and 3.85g of heptane, and heated using an oil bath, and then 105μL of 4% by mass trioctylamine 2-propanol solution and 52μL of 4% by mass hexachloroplatinic acid hexahydrate 2-propanol solution were added. Then, the reaction was carried out for 4 hours under reflux. After the reaction, 17.90g of ion-exchanged water, 7.16g of 2-propanol, and 3.580g of heptane were mixed and stirred. After standing, the mixture was separated into two layers, and the lower layer was discarded. After that, the mixture of ion-exchanged water, 2-propanol, and heptane, stirring, and discarding the lower layer were repeated twice, and the upper layer was distilled under reduced pressure to obtain 4.73 g of a transparent gel-like substance. 1H NMR analysis confirmed that it was the compound represented by formula (1).

[0043] 1H NMR analysis Peak area value of 2H of terminal double bond at 5.54 and 6.10 ppm (1.00 + 1.00 = 2.00) 11H area value (19.38) derived from phosphorylcholine group at 3.34 ppm Area value of 8H from hexyl group at 1.31 ppm (32.44) Peak area value (421.30) derived from siloxane at 0.16 ppm From the above, it was calculated that in the structural formula (1), a≒70, b=2, c=4, p=q=0, X is -CH2CH2-, and the number average molecular weight Mn is ≒4600. The number average molecular weight was measured using gel permeation chromatography (GPC) and calculated under the following measurement conditions using PMMA (polymethyl methacrylate) as the standard. Eluent: Methanol, chloroform mixed solution (methanol / chloroform = 4 / 6 (vol% / vol%) + 0.5wt% LiBr) Column: Polargel-L x 1, Polargel-M x 1 (connected in series) ·Flow rate: 1.0mL / min Detector: Differential refractometer Column oven temperature: 40℃

[0044] [Examples 1-2 to 1-6] Instead of 1-hexene used in [Synthesis Example 1], propene or isohexene was used, and five equivalents of these were reacted with 1,3,5,7-tetramethylcyclotetrasiloxane to synthesize alkyl group-containing cyclic silicone of formula (7) in which the R group portion is a propyl group or an isohexyl group. Using compounds of formula (7) with different R group portions, hydrosilyl group-containing methacrylic silicones at both ends of formula (4) were synthesized by varying the molecular weight and hydrosilyl group content. Next, Examples 1-2 to 1-6 were carried out in the same manner as in Example 1-1, except that the amount of the compound of formula (6) charged was changed in proportion to the concentration of the hydrosilyl group. The calculated results of the molar ratio and number average molecular weight of the structural units of formula (1) in Examples 1-1 to 1-6 are shown in Table 1. [Table 1]

[0045] [Example 2-1] DMAA 9.89 parts by mass, HBMA 9.89 parts by mass, NVP 29.71 parts by mass, the compound prepared in Example 1-1 19.81 parts by mass, MAA 0.99 parts by mass, ETS 29.71 parts by mass, HexOH 29.71 parts by mass, TEGDMA 0.99 parts by mass, and AIBN 0.49 parts by mass were stirred and mixed at room temperature for 1 hour, and dissolved uniformly to obtain a monomer composition. The composition is shown in Table 2.

[0046] 0.3 g of the above monomer composition was poured into a 25 mm x 70 mm x 0.2 mm cell sandwiched between two polypropylene plates using a 0.1 mm thick polyethylene terephthalate sheet as a spacer, and placed in an oven. After replacing the atmosphere in the oven with nitrogen, the temperature was raised to 100°C and maintained at that temperature for 2 hours to polymerize the composition and obtain a polymer.

[0047] The above polymer was immersed in 40 g of 2-propanol for 4 hours, and then immersed in 50 g of ion-exchanged water for 4 hours to remove unreacted materials and purify it. The polymer was then immersed in physiological saline according to ISO-18369-3 to obtain a transparent film-like sample. The composition uniformity and polymer transparency of the sample were observed, and both were good, as shown in Table 2.

[0048] The water content, surface hydrophilicity (WBUT measurement), stability test, and water content in the stability test of the film-like sample were evaluated by the above-mentioned methods. The results are shown in Table 2.

[0049] [Examples 2-2 to 2-7] Examples 2-2 to 2-7 were carried out in the same manner as Example 2-1, except that the compositions shown in Table 2 were used. As in Example 2-1, the composition uniformity, polymerization transparency, surface hydrophilicity, water content, and stability were evaluated, and the results are shown in Table 2. All were confirmed to have composition uniformity and polymerization transparency. In addition, the water film retention time in the WBUT measurement was 15 seconds or longer, and it was confirmed that the surface had sufficient hydrophilicity. Furthermore, the change in water content was within 1% or 2%, and it was also confirmed that the sample was stable.

[0050] [Comparative Example 2-1] As shown in Table 3, when 29.71 parts by mass of FM-7721, a comparative compound of formula (1), was used instead of the compound represented by formula (1), a homogeneous solution was not obtained (referred to as poor in Table 3).

[0051] [Comparative Example 2-2] As shown in Table 3, when 9.90 parts by mass of FM-7721, which is a comparative compound of formula (1), was used instead of the compound represented by formula (1), composition uniformity and polymer transparency were confirmed, but the surface hydrophilicity was low and the change in water content in the stability test exceeded 2%, indicating that the stability was insufficient (evaluation C).

[0052] Therefore, it was confirmed that the polymer obtained by polymerizing the monomer composition containing the polysiloxane monomer represented by formula (1) exhibits good surface hydrophilicity and has sufficient stability even in the presence of methacrylic acid.

[0053] [Table 2]

[0054] [Table 3]

[0055] From the above, it has been confirmed that the phosphorylcholine group-containing polysiloxane monomer of the present invention, when copolymerized with a polymerizable monomer such as a hydrophilic monomer, satisfies surface hydrophilicity and has stability due to its good compatibility with methacrylic acid, and is therefore useful as a polysiloxane monomer used as a raw material for ophthalmic devices. [Industrial Applicability]

[0056] The phosphorylcholine group-containing polysiloxane monomer of the present invention, when copolymerized with a polymerizable monomer such as methacrylic acid or a hydrophilic monomer other than methacrylic acid, can give a polymer that exhibits surface hydrophilicity and sufficient stability for an ophthalmic device.

Claims

1. A phosphorylcholine group-containing polysiloxane monomer represented by formula (1): 【Chemistry 1】 (In the formula, a represents an integer of 20 to 500; b represents an integer of 1 to 70; c represents an integer of 1 to 70; d represents 0 or 1; p and q each represent 0 or 1; and X represents -CH ２ -or-CH ２ CH ２ -, and R represents an alkyl group having 2 to 8 carbon atoms.

2. A method for producing a phosphorylcholine group-containing polysiloxane monomer represented by formula (1), comprising a step of addition reacting a hydrosilyl group-containing, both-terminated methacrylic silicone represented by formula (4) with a phosphorylcholine compound represented by formula (6). 【Chemistry 2】 (In the formula, a represents an integer of 20 to 500; b represents an integer of 1 to 70; c represents an integer of 1 to 70; d represents 0 or 1; p and q each represent 0 or 1; and X represents -CH ２ -or-CH ２ CH ２ -, and R represents an alkyl group having 2 to 8 carbon atoms. 【Chemistry 3】 (In the formula, a represents an integer of 20 to 500, b represents an integer of 1 to 70, c represents an integer of 1 to 70, p and q each represent 0 or 1, and R represents an alkyl group having 2 to 8 carbon atoms.) 【Chemistry 4】 (wherein d is 0 or 1; Z is CH ２ =CHCH ２ - or CH ２ =CH-.)

3. A monomer composition comprising 10% by mass to 45% by mass of a phosphorylcholine group-containing polysiloxane monomer represented by formula (1), 10% by mass to 40% by mass of a hydroxyl group-containing siloxanyl group-containing monomer represented by formula (8) or formula (9), 0.1% by mass to 5% by mass of methacrylic acid, and 30% by mass to 70% by mass of a hydrophilic monomer other than methacrylic acid. 【Chemistry 5】 (In the formula, a represents an integer of 20 to 500; b represents an integer of 1 to 70; c represents an integer of 1 to 70; d represents 0 or 1; p and q each represent 0 or 1; and X represents -CH ２ -or-CH ２ CH ２ -, and R represents an alkyl group having 2 to 8 carbon atoms. 【Chemistry 6】 【Chemistry 7】

4. A polymer obtained by polymerizing the monomer composition according to claim 3.

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