Polysiloxane compound, polymer, hydrogel, medical material, and method for producing polysiloxane compound

Abstract

The invention relates to a polysiloxane compound containing more than one (methyl) acryloyloxy group in one molecule, which is characterized in that the end of the side chain of the polysiloxane compound is provided with tertiary hydroxyl. As a result, it is possible to provide a polysiloxane compound suitable for use in a medical material, a polymer using the polysiloxane compound, a hydrogel containing the polymer, a medical material containing the polymer, and a method for producing the polysiloxane compound.

Description

Technical Field

[0001] This invention relates to a polysiloxane compound, a polymer, a hydrogel, a medical material, and a method for preparing the polysiloxane compound. Background Technology

[0002] Monomers containing siloxanes have long been known to be used as compounds in medical materials, including ophthalmic devices. For example, 3-[tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS) is widely used as a monomer for ophthalmic devices. Polymers obtained by copolymerizing this TRIS with hydrophilic monomers such as N,N-dimethylacrylamide or N-vinyl-2-pyrrolidone possess the advantageous characteristic of high oxygen permeability. However, it cannot be said that highly hydrophobic siloxane monomers are highly compatible with these hydrophilic monomers; phase separation can occur when preparing hydrogels as medical materials, leading to a white turbidity.

[0003] Patent document 1 describes siloxanes having primary or secondary hydroxyl groups as shown in the following formulas (a) and (a'). [Chemical Formula 1]

[0004] In addition, Patent Document 2 describes a siloxane having primary and secondary hydroxyl groups on the siloxane side chain, as shown in the following formula (b). [Chemical Formula 2]

[0005] These compounds exhibit good hydrophilicity due to the presence of hydroxyl groups within their molecules. Therefore, they possess the advantage of excellent compatibility with hydrophilic monomers.

[0006] However, in the case of hydrogels prepared using the aforementioned (poly)siloxanes and compounds having primary or secondary hydroxyl groups, these highly reactive hydroxyl groups can sometimes lead to undesirable results. For example, free radical addition may occur to these hydroxyl groups, forming a cross-linked structure caused by hydroxyl radicals. This can result in poor appearance, unexpected increases in hardness, or decreased softness. Therefore, existing siloxane compounds cannot provide medical materials with beneficial transparency, hydrophilicity, and sufficient strength. Thus, the need for compounds and compositions that overcome these drawbacks remains. Existing technical documents Patent documents

[0007] Patent Document 1: Japanese Patent Application Publication No. 2005-170827 Patent Document 2: Japanese Patent Application Publication No. 2021-073346 Invention Summary The problem that the invention aims to solve

[0008] The purpose of this invention is to provide a polysiloxane compound suitable for medical materials, a polymer using the polysiloxane compound, a hydrogel containing the polymer, a medical material containing the polymer, and a method for preparing the polysiloxane compound. Technical means to solve the problem

[0009] To address the aforementioned problems, this invention provides a polysiloxane compound containing one or more (meth)acryloyloxy groups in one molecule, wherein the polysiloxane compound has tertiary hydroxyl groups at the end of its side chain.

[0010] Such polysiloxane compounds can be used in medical materials.

[0011] In addition, in this invention, the polysiloxane compound is preferably a compound represented by the following general formula (1). [Chemical Formula 3] (In the formula, Z are independent organic groups with 1 to 20 carbon atoms, R are independent monovalent hydrocarbon groups with 1 to 6 carbon atoms, R' are independent monovalent hydrocarbon groups with 3 to 20 carbon atoms and a tertiary hydroxyl group at the end, the structural chain of the group may contain ether bonds, n is an integer from 0 to 200, and m is an integer from 3 to 200. However, more than one Z is (meth)acryloyloxy.)

[0012] Such polysiloxane compounds would be more suitable for medical materials.

[0013] Furthermore, in this invention, it is preferable that in the general formula (1), Z is a group represented by the following general formula (2). [Chemical Formula 4] (In the formula, X is a hydrogen atom or a methyl group, and the dashed line represents a bond with a silicon atom.)

[0014] Such polysiloxane compounds can be further applied to medical materials.

[0015] Furthermore, in the present invention, in the general formula (1), R is preferably methyl.

[0016] The preferred polysiloxane compound of the present invention is such a compound.

[0017] Furthermore, in this invention, in the general formula (1), R' is preferably a group represented by the following general formula (3) or the following formula (4). [Chemical Formula 5] (In general formula (3), k represents an integer from 0 to 5; in general formula (3) and formula (4), the dashed line represents the bond with silicon atoms.)

[0018] More preferably, the polysiloxane compound of the present invention is such a compound.

[0019] In this case, k is preferably 0 or 1 in the general formula (3).

[0020] Such polysiloxane compounds can be further applied to medical materials.

[0021] In addition, in this invention, it is preferred that in the general formula (1), n ​​is an integer from 0 to 100, m is an integer from 3 to 100, and m / (n+m) is 0.15 or more.

[0022] Such polysiloxane compounds can be further applied to medical materials.

[0023] In this case, in the general formula (1), m / (n+m) is preferably 0.3 or more.

[0024] Such polysiloxane compounds can be further applied to medical materials.

[0025] In addition, this invention provides a polymer that is a polymer of the polysiloxane compound described above.

[0026] Such polymers are well compatible with other compounds that have polymerizable groups such as (meth)acryloyloxy groups.

[0027] At this point, the preferred mass percentage of the polysiloxane compound is 20% or more of the total mass of the polymer.

[0028] If it is such a polymer, it is likely to exhibit the characteristics of polysiloxane compounds.

[0029] In addition, this invention provides a hydrogel or medical material comprising the polymer described above.

[0030] The polymers of this invention are suitable for the following applications.

[0031] In addition, this invention provides a method for preparing a polysiloxane compound, which includes the following steps: A compound containing unsaturated groups and tertiary hydroxyl groups at the end is subjected to a hydrosilylation reaction with an organohydrogen polysiloxane compound represented by the following general formula (5) to obtain a polysiloxane compound represented by the following general formula (1). [Chemical Formula 6] (In the formula, Z are independent organic groups with 1 to 20 carbon atoms, R are independent monovalent hydrocarbon groups with 1 to 6 carbon atoms, n is an integer from 0 to 200, and m is an integer from 3 to 200. However, more than one Z is (meth)acryloyloxy.) [Chemical Formula 7] (In the formula, R' is a monovalent hydrocarbon group with 3 to 20 carbon atoms at the end and a tertiary hydroxyl group; the structural chain of the group may contain ether bonds. Z, R, n, and m are as described above.)

[0032] If such a method is used to prepare polysiloxane compounds, then the polysiloxane compounds of the above general formula (1) can be obtained with high purity.

[0033] In this case, it is preferable that the compound containing unsaturated groups and tertiary hydroxyl groups at the end is set to 1.0 to 3.0 molar equivalents relative to the hydrosiloxy group.

[0034] If such a method is used to prepare polysiloxane compounds, polysiloxane compounds can be obtained economically and with high purity.

[0035] At this point, it is preferable to set the content of the polysiloxane compound represented by the general formula (1) to be 90% or more.

[0036] If such a polysiloxane compound is present, it can be further applied to medical materials. Invention Effects

[0037] The polysiloxane compounds of the present invention, by having tertiary hydroxyl groups at the ends of their side chains, not only exhibit excellent compatibility with hydrophilic monomers but also do not result in a decrease in transparency, unexpected increase in hardness, or decrease in softness when used as medical materials. Furthermore, the (co)polymers comprising repeating units formed by the polymerization of (meth)acryloyloxy groups from the polysiloxane compounds of the present invention possess desirable strength. The polysiloxane compounds of the present invention are useful as monomers for medical materials. Detailed Implementation

[0038] As described above, there is a need to develop a polysiloxane compound suitable for medical materials, a polymer using the polysiloxane compound, a hydrogel containing the polymer, a medical material containing the polymer, and a method for preparing the polysiloxane compound.

[0039] To address the aforementioned problems, the inventors conducted intensive research and discovered that a polysiloxane compound containing one or more (meth)acryloyloxy groups in one molecule, and having tertiary hydroxyl groups at the end of the side chain of the polysiloxane compound, exhibits excellent compatibility with other hydrophilic monomers. Furthermore, it was discovered that the (co)polymer of the polysiloxane compound and the hydrophilic monomer possesses excellent flexibility.

[0040] That is, the present invention is a polysiloxane compound containing one or more (meth)acryloyloxy groups in one molecule, and is a polysiloxane compound having tertiary hydroxyl groups at the end of the side chain of the polysiloxane compound.

[0041] The present invention will now be described in detail, but the present invention is not limited thereto.

[0042] [Polysiloxane compounds] The present invention relates to a polysiloxane compound containing one or more (meth)acryloyloxy groups in one molecule, and is a compound having tertiary hydroxyl groups at the end of the side chain of the polysiloxane compound.

[0043] The compound has a polysiloxane structure and is characterized by having tertiary hydroxyl groups at the ends of its side chains. In the polysiloxane compound of the present invention, these tertiary hydroxyl groups become hydrophilic groups, and there is steric restriction therein. Therefore, it is presumed that side reactions during the reaction can be suppressed. Furthermore, in polymers (copolymers) comprising repeating units formed by the polymerization of (meth)acryloyloxy groups using the polysiloxane compound of the present invention, strong hydrogen bonding occurs due to the directionality of the hydrogen bonds, resulting in high strength. That is, the polysiloxane compound of the present invention has high compatibility with hydrophilic monomers, providing ideal strength in the formed (copolymer), and further preventing unexpected increases in hardness or decreases in softness.

[0044] Particularly preferred is that the polysiloxane compound is a compound represented by the following general formula (1). [Chemical Formula 8] (In the formula, Z are independent organic groups with 1 to 20 carbon atoms, R are independent monovalent hydrocarbon groups with 1 to 6 carbon atoms, R' are independent monovalent hydrocarbon groups with 3 to 20 carbon atoms having a tertiary hydroxyl group at the end, the structural chain of the group may contain ether bonds, n is an integer from 0 to 200, and m is an integer from 3 to 200. However, more than one Z is (meth)acryloyloxy.)

[0045] In the above general formula (1), Z is an organic group with 1 to 20 carbon atoms, and preferably is a group shown in the following general formula (2). [Chemical Formula 9] (In the formula, X is a hydrogen atom or a methyl group, and the dashed line represents a bond with a silicon atom.)

[0046] In the above general formula (1), R is a monovalent hydrocarbon group having 1 to 6 carbon atoms, which are independent of each other. Examples of monovalent hydrocarbon groups include alkyl groups such as methyl, ethyl, propyl, n-butyl, tert-butyl, pentyl, and hexyl; cyclopentyl and cyclohexyl; and aryl groups such as phenyl. R is preferably an alkyl group having 1 to 4 carbon atoms, and is more preferably methyl.

[0047] In the above general formula (1), R' is independently a monovalent hydrocarbon group with 3 to 20 carbon atoms having a tertiary hydroxyl group at the end, and the structural chain of the group may contain ether bonds. The R' is preferably a group shown in the following general formula (3) or the following formula (4). [Chemical Formula 10] (In general formula (3), k represents an integer from 0 to 5; in general formula (3) and formula (4), the dashed line represents the bond with silicon atoms.)

[0048] In the above general formula (3), k is an integer from 0 to 5, preferably 0 or 1.

[0049] In the above general formula (1), n ​​is an integer from 0 to 200, and m is an integer from 3 to 200. Preferably, n is an integer from 0 to 100, m is an integer from 3 to 100, and m / (n+m) is 0.15 or more. More preferably, m / (n+m) is 0.3 or more. Even more preferably, m / (n+m) is 0.3 to 1.0.

[0050] [Preparation method of polysiloxane compounds] The preparation method of the polysiloxane compound represented by the above general formula (1) will be described below. This invention provides a method for preparing a polysiloxane compound, comprising the following steps: A compound containing unsaturated groups and tertiary hydroxyl groups at the end is subjected to a hydrosilylation reaction with an organohydrogen polysiloxane compound of the following general formula (5) to obtain the polysiloxane compound of the above general formula (1). [Chemical Formula 11] (In the formula, Z are independent organic groups with 1 to 20 carbon atoms, R are independent monovalent hydrocarbon groups with 1 to 6 carbon atoms, n is an integer from 0 to 200, and m is an integer from 3 to 200. However, more than one Z is (meth)acryloyloxy.)

[0051] The method for preparing the polysiloxane compound of the present invention is characterized by using a compound having an unsaturated terminal group and a tertiary hydroxyl group as a raw material. In the method for preparing the polysiloxane compound of the present invention, since the hydroxyl group is a tertiary hydroxyl group, undesirable side reactions caused by the hydroxyl group in the hydrosilylation reaction can be suppressed. Therefore, the polysiloxane compound of the present invention can be obtained with high purity.

[0052] The hydrosilylation reaction can be carried out according to existing known methods. In this invention, a compound having a terminal unsaturated group and a tertiary hydroxyl group of, for example, more than 1 molar equivalent can be added to the organohydropolysiloxane compound of the above general formula (5) to carry out the reaction. Although there is no particular limitation on the reaction temperature, it is preferred to be a temperature not exceeding about the boiling point of the solvent used. For example, it can be carried out at a temperature of about 0°C to about 150°C. The hydrosilylation reaction can be carried out in the presence of a solvent, a hydrosilylation catalyst, or a stabilizer. The solvent, the hydrosilylation catalyst, and the stabilizer can be existing known and are not particularly limited.

[0053] In the above-described hydrosilylation reaction, it is preferable to add at least 1 molar equivalent of a compound having a terminal unsaturated group and a tertiary hydroxyl group to the hydrosiloxy unit. More preferably, 1.0 to 3.0 molar equivalents are used; even more preferably, 1.2 to 2.0 molar equivalents are used; and particularly preferably, 1.5 to 2.0 molar equivalents are used. By adding at least 1 molar equivalent of a compound having a terminal unsaturated group and a tertiary hydroxyl group to the hydrosiloxy unit, residual hydrosiloxy unit and side reactions can be suppressed. Furthermore, while there is no upper limit, from the perspective of yield and economy, 3.0 molar equivalents or less are preferred.

[0054] (Hydrosilane catalyst) The hydrogenation silylation catalyst is, for example, a noble metal catalyst, and particularly preferred is a platinum catalyst derived from chloroplatinic acid. In particular, it can be a catalyst whose stability is improved by completely neutralizing the hydrogen ions of chloroplatinic acid with sodium bicarbonate. More preferably, for example, is a complex of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane with sodium bicarbonate neutralization of chloroplatinic acid (Karstedt catalyst).

[0055] The amount of hydrogen silanization catalyst added is only the amount of catalyst sufficient to carry out the above-mentioned hydrogen silanization reaction. For example, relative to the mass of the organohydropolysiloxane compound shown in the above general formula (5), in platinum equivalents, a complex of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane and sodium bicarbonate neutralization of chloroplatinic acid can be used.

[0056] (solvent) Solvents include, for example: glycol ether solvents such as methyl cellosolve, ethyl cellosolve, isopropyl cellosolve, butyl cellosolve, propylene glycol monomethyl ether, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, polyethylene glycol monomethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, and polyethylene glycol dimethyl ether; ester solvents such as ethyl acetate, butyl acetate, amyl acetate, ethyl lactate, and methyl benzoate; and linear hexane and linear heptane. The solvents include aliphatic hydrocarbon solvents such as straight-chain octane; alicyclic hydrocarbon solvents such as cyclohexane and ethylcyclohexane; ketone solvents such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; aromatic hydrocarbon solvents such as benzene, toluene, and xylene; petroleum solvents; and alcohol solvents such as methanol, ethanol, straight-chain propanol, isopropanol, straight-chain butanol, isobutanol, tert-butanol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, and polyethylene glycol. One of the solvents may be used alone, or two or more may be used in combination.

[0057] (Stabilizer) Stabilizers include, for example, phenolic antioxidants, phosphorus antioxidants, amine antioxidants, and sulfur antioxidants. While there are no specific limitations on phenolic antioxidants, examples include compounds selected from p-methoxyphenol, di-tert-butyl-p-cresol, pyrogallol, tert-butylcatechol, 4,4'-thiobis(3-methyl-6-tert-butylphenol), 2,2'-methylenebis(4-methyl-6-tert-butylphenol), phenolic resins, and cresol resins. As phosphorus antioxidants, although there are no specific limitations, examples include: tris[2-[[2,4,8,10-tetra(1,1-dimethylethyl)dibenzo[d,f][1,3,2]]dioxophosphatidyl-6-yl]oxy]ethyl]amine, tris[2-[(4,6,9,11-tetra-tert-butyldibenzo[d,f][1,3,2]dioxophosphatidyl-2-yl)oxy]ethyl]amine, and ethyl bis(2,4-di-tert-butyl-6-methylphenyl) phosphite, etc. While not specifically limited, examples of amine antioxidants include: tri- or tetra-C1-3 alkylpiperidine or its derivatives, bis(2,2,6,6-tetramethyl-4-piperidinyl)oxalate, 1,2-bis(2,2,6,6-tetramethyl-4-piperidinoxy)ethane, phenylnaphthylamine, N,N'-diphenyl-1,4-phenylenediamine, and N-phenyl-N'-cyclohexyl-1,4-phenylenediamine. While not specifically limited, examples of sulfur antioxidants include: dilauryl thiodipropionate and distearate thiodipropionate. The stabilizer may be used alone or in combination of two or more.

[0058] In the above-described hydrosilylation reaction, the reaction endpoint can be determined using currently known methods. For example, it can be determined by... 1The disappearance of the peak of the raw material compound can be confirmed by methods such as H-NMR analysis, thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), or gas chromatography (GC). After the reaction is complete, purification can be carried out using existing known methods. For example, the product can be separated by washing the organic layer with water and removing the solvent. Alternatively, vacuum distillation or activated carbon treatment can be used.

[0059] An example of the preparation method of the polysiloxane compound of the present invention is as follows: 1 molar equivalent of the organohydrogen polysiloxane compound of the above general formula (5), 1.5 molar equivalent of the compound with terminal unsaturated groups and tertiary hydroxyl groups, and a toluene solution of sodium bicarbonate chloroplatinate neutralization-vinylsiloxane complex (platinum content 0.5 wt%) with a mass of 10 ppm relative to the organohydrogen polysiloxane compound in platinum equivalents are added, and the mixture is heated and stirred at 80°C. The reaction is completed by allowing it to react for about 6 hours. Additionally, the compound with terminal unsaturated groups and tertiary hydroxyl groups, or the generated compound, can be subjected to [further processing / treatment] during this period. 1 The reaction process was confirmed by monitoring such as H-NMR analysis. After the reaction was completed, unreacted raw materials could be removed by vacuum distillation to obtain the polysiloxane compound represented by the above general formula (1).

[0060] [Purity of polysiloxane compounds] The purity (content) of the polysiloxane compound of the present invention can be confirmed by, for example, gel permeation chromatography (GPC). The determination can be performed according to existing known methods; although not particularly limited, it is preferable to use an eluent containing the polysiloxane compound of the present invention. Furthermore, existing known detectors, such as differential refractive index (RI) detectors, can also be used. The purity of the polysiloxane compound can be calculated from the area ratio of the target analyte on the GPC chromatogram. In this case, it is preferable to set the content of the polysiloxane compound to 90% or more, as this more readily reveals the characteristics of the polysiloxane compound of the present invention.

[0061] [polymer] This invention provides a polymer, which is a polymer of the polysiloxane compound described above. The polysiloxane compound of this invention provides a polymer (polymer) comprising repeating units formed by the (addition) polymerization of the (meth)acryloyloxy group of the polysiloxane compound. The polysiloxane compound of this invention has good compatibility with other compounds having polymerizable groups such as (meth)acryloyloxy groups (hereinafter referred to as polymerizable monomers or hydrophilic monomers). Therefore, by copolymerizing with polymerizable monomers, a colorless and transparent copolymer can be obtained. Alternatively, the polysiloxane compound can also be polymerized alone.

[0062] When preparing a copolymer comprising repeating units formed by polymerization of the polysiloxane compound of the present invention with other polymerizable (hydrophilic) monomers, the preferred proportion of the polysiloxane compound of the present invention is that the repeating units formed by the polysiloxane compound of the present invention account for 20% or more of the total polymer mass. That is, the preferred mass proportion of the polysiloxane compound is 20% or more of the total polymer mass. More specifically, relative to a total of 100 parts by mass of the polysiloxane compound of the present invention and the polymerizable (hydrophilic) monomers, the preferred amount of repeating units formed by (meth)acryloyloxy (addition) polymerization of the polysiloxane compound of the present invention is 20 to 80 parts by mass, more preferably 30 to 60 parts by mass. If the mass proportion of the repeating units is 20% or more, the characteristics of the polysiloxane compound of the present invention are more readily exhibited.

[0063] Examples of polymerizable monomers include, for example: acrylic acid, methyl methacrylate, ethyl methacrylate, polyethylene glycol dimethacrylate, polyalkylene glycol mono(meth)acrylate, polyalkylene glycol monoalkyl ether(meth)acrylate, trifluoroethyl(meth)acrylate, 2-hydroxyethyl(meth)acrylate, 2,3-dihydroxypropyl(meth)acrylate, and other acrylic acid monomers; acrylic acid derivatives such as N,N-dimethylacrylamide, N,N-diethylacrylamide, N-acryloylmorpholine, and N-methyl(meth)acrylamide; other unsaturated aliphatic or aromatic compounds such as N-vinylpyrrolidone, for example, crotonic acid, cinnamic acid, and vinylbenzoic acid; and siloxane monomers having polymerizable groups such as (meth)acryloyl groups. These can be used individually or in combination of two or more.

[0064] The copolymerization of the polysiloxane compound of the present invention with the other polymerizable monomers described above can be carried out according to existing known methods. For example, known polymerization initiators such as thermal polymerization initiators or photopolymerization initiators can be used. Examples of such polymerization initiators include: 2-hydroxy-2-methyl-1-phenylpropane-1-one, azobisisobutyronitrile, azobis(dimethyl)valerate, benzoyl peroxide, tert-butyl hydroperoxide, cumene hydroperoxide, 2,2'-azobis(2-methylpropanediamine) dihydrochloride, etc. These polymerization initiators can be used alone or in combination of two or more. The preferred amount of polymerization initiator is 0.001 to 2 parts by mass relative to 100 parts by mass of the total polymerizing components, and more preferably 0.01 to 1 part by mass.

[0065] The polymer comprising repeating units formed by the polymerization of the polysiloxane compound of the present invention (meth)acryloyloxy group exhibits excellent hydrophilicity. Furthermore, the hydrogel obtained from said polymer possesses high transparency and high strength. Additionally, medical materials can also be obtained from said polymer. Therefore, the polysiloxane compound of the present invention is suitable for preparing medical materials, such as ophthalmic devices, contact lenses, intraocular lenses, and artificial corneas. There are no particular limitations on the preparation method of the medical materials using said polymer; any existing known methods for preparing medical materials can be followed. For example, when forming the shape of lenses such as contact lenses and intraocular lenses, machining methods or molding methods can be used. [Example]

[0066] The following examples of synthesis, embodiments, and comparative examples illustrate the present invention in more detail, but the present invention is not limited to the embodiments described below. In the following embodiments, 1 The H-NMR analysis was performed using an ECS400 manufactured by JEOL, with deuterated chloroform as the determination solvent. In addition, all gel permeation chromatography (GPC) determinations were performed under the following conditions. Measurement device: Tosoh HLC-8320 (RI detector) Column: TSKgel Guardcolumn SuperH-H TSKgel SuperH2500 TSKgel SuperHM-N Temperature: 40℃ Eluent: Tetrahydrofuran (THF) Flow rate: 0.6 mL / min Sample concentration: 0.3% by mass (THF solution) Injection volume: 50 μL

[0067] Synthesis example 1 In a 500 mL three-necked flask equipped with a Demrod condenser and a thermometer, 80.0 g of allyl alcohol, 100.0 g of isobutylene oxide, and 46.6 g of potassium tert-butoxide were added. The mixture was heated to 50 °C and allowed to mature for 24 hours. After the reaction, the mixture was washed three times with a 10% sodium chloride aqueous solution. Unreacted reactants were removed by distillation at an internal temperature of 150 °C, followed by simple distillation to obtain 134.1 g of an unsaturated compound with tertiary hydroxyl groups as shown in formula (A) below. [Chemical Formula 12]

[0068] Synthesis example 2 The 80.0 g allyl alcohol in Synthesis Example 1 was replaced with 141.0 g allyl ethylene glycol, and the same procedure was performed to obtain 145.5 g of the unsaturated compound with tertiary hydroxyl groups as shown in formula (B) below. [Chemical Formula 13]

[0069] Synthesis example 3 In a 500 mL three-necked flask equipped with a Demrod condenser and a thermometer, 100.0 g of 3-methyl-1,3-butanediol, 95.6 g of allyl chloride, 107.6 g of potassium tert-butoxide, and 100.0 g of toluene were added. The mixture was heated to 50 °C and allowed to mature for 24 hours. After the reaction, the mixture was washed three times with a 10% sodium chloride aqueous solution. Unreacted reactants were removed by distillation at an internal temperature of 220 °C, followed by simple distillation to obtain 113.1 g of the unsaturated compound shown in formula (C) below. [Chemical Formula 14]

[0070] Example 1-1 In a 500 mL three-necked flask equipped with a Demrod condenser and a thermometer, 50.0 g of a hydrosiloxane compound of formula (100) below, 19.3 g of an unsaturated compound of formula (A) above (molar ratio of unsaturated compound to hydrosiloxane unit = 1.5), 100.0 g of toluene, and 0.03 g of a toluene solution of sodium bicarbonate chloroplatinate neutralization-vinylsiloxane complex (platinum content 0.5 wt%) were added. The mixture was heated to 80 °C and allowed to mature for 6 hours. After the reaction, the solvent and unreacted raw materials were removed by vacuum distillation at an internal temperature of 100 °C, yielding a colorless and transparent liquid. The yield was 58.8 g. 1 ¹H-NMR confirmed that it was a compound represented by the formula (100A). GPC analysis was performed, and the area of ​​the target compound was calculated to be 100%. [Chemical Formula 15] [Chemical Formula 16]

[0071] Examples 1-2 Except that 19.3 g of the unsaturated compound shown in formula (A) above was replaced with 21.4 g of the unsaturated compound shown in formula (C) above (molar ratio of unsaturated compound to hydrosiloxy unit = 1.5), a colorless and transparent liquid was obtained using the same method as in Example 1-1. The yield was 61.2 g. 1 ¹H-NMR confirmed that it was a compound represented by the formula (100C). GPC analysis was performed, and the area of ​​the target compound was calculated to be 100%. [Chemical Formula 17]

[0072] Examples 1-3 In Example 1-1, except that 50.0 g of the hydrosiloxane compound of formula (100) above was replaced with 50.0 g of the hydrosiloxane compound of formula (101) below, and 19.3 g of the unsaturated compound of formula (A) above was replaced with 95.2 g (molar ratio of unsaturated compound to hydrosiloxane unit = 2.0), a colorless and transparent solid was obtained by the same method as in Example 1-1. The yield was 103.4 g. 1 ¹H-NMR confirmed that it was a compound represented by the formula (101A). GPC analysis was performed, and the area of ​​the target compound was calculated to be 100%. [Chemical Formula 18] [Chemical Formula 19]

[0073] Examples 1-4 In Example 1-1, except that 50.0 g of the hydrosiloxane compound shown in formula (100) above was replaced with 20.0 g of the hydrosiloxane compound shown in formula (102) below, and 19.3 g of the unsaturated compound shown in formula (A) above was replaced with 99.0 g (molar ratio of unsaturated compound to hydrosiloxane unit = 3.0), a colorless and transparent solid was obtained by the same method as in Example 1-1. The yield was 43.4 g. 1 ¹H-NMR confirmed that it was a compound represented by the formula (102A). GPC analysis was performed, and the area of ​​the target compound was calculated to be 100%. [Chemical Formula 20] [Chemical Formula 21]

[0074] Examples 1-5 In Example 1-1, a colorless, transparent solid was obtained by replacing 50.0 g of the hydrosiloxane compound shown in formula (100) with 20.0 g of the hydrosiloxane compound shown in formula (102), and replacing 19.3 g of the unsaturated compound shown in formula (A) with 88.3 g of the unsaturated compound shown in formula (B) (molar ratio of unsaturated compound to hydrosiloxane unit = 2.0), using the same method as in Example 1-1. The yield was 50.7 g. 1 ¹H-NMR confirmed that it was a compound represented by the formula (102B). GPC analysis was performed, and the area of ​​the target compound was calculated to be 100%. [Chemical Formula 22]

[0075] Examples 1-6 In Example 1-1, a colorless, transparent solid was obtained by replacing 50.0 g of the hydrosiloxane compound of formula (100) above with 30.0 g of the hydrosiloxane compound of formula (103) below, and replacing 19.3 g of the unsaturated compound of formula (A) above with 75.4 g (molar ratio of unsaturated compound to hydrosiloxane unit = 2.0), using the same method as in Example 1-1. The yield was 60.0 g. 1 ¹H-NMR confirmed that it was a compound represented by the formula (10³A). GPC analysis was performed, and the area of ​​the target compound was calculated to be 100%. [Chemical Formula 23] [Chemical Formula 24]

[0076] Examples 1-7 In Example 1-1, a colorless, transparent solid was obtained by replacing 50.0 g of the hydrosiloxane compound shown in formula (100) with 30.0 g of the hydrosiloxane compound shown in formula (103), and replacing 19.3 g of the unsaturated compound shown in formula (A) with 62.6 g of the unsaturated compound shown in formula (C) (molar ratio of unsaturated compound to hydrosiloxane unit = 1.5), using the same method as in Example 1-1. The yield was 60.2 g. 1 ¹H-NMR confirmed that it was a compound represented by the formula (10³C). GPC analysis was performed, and the area of ​​the target compound was calculated to be 100%. [Chemical Formula 25]

[0077] Examples 1-8 In Example 1-1, a colorless, transparent solid was obtained by replacing 50.0 g of the hydrosiloxane compound of formula (100) above with 30.0 g of the hydrosiloxane compound of formula (104) below, and replacing 19.3 g of the unsaturated compound of formula (A) above with 45.5 g (molar ratio of unsaturated compound to hydrosiloxane unit = 1.5) using the same method as in Example 1-1. The yield was 67.7 g. 1 ¹H-NMR confirmed that it was a compound represented by the formula (10⁴A). GPC analysis was performed, and the area of ​​the target compound was calculated to be 100%. [Chemical Formula 26] [Chemical Formula 27]

[0078] Comparative Example 1-1 In a 500 mL three-necked flask equipped with a Demrod condenser and a thermometer, 50.0 g of the hydrosiloxane compound shown in formula (100) above, 19.6 g of 3-allyloxy-1,2-propanediol (molar ratio of unsaturated compound to hydrosiloxane unit = 1.5), 100.0 g of toluene, and 0.03 g of a toluene solution of sodium bicarbonate chloroplatinate neutralization-vinylsiloxane complex (platinum content 0.5 wt%) were added. The mixture was heated to 80 °C and matured for 6 hours. After the reaction, the solvent was removed by vacuum distillation at an internal temperature of 80 °C. 50 g of n-hexane was added, and the mixture was washed three times with 50 g of acetonitrile. After washing, the solvent was removed by vacuum distillation at an internal temperature of 80 °C, yielding a white, turbid liquid. The yield was 32.2 g. 1 ¹H-NMR confirmed that it was a compound represented by the following formula (200). GPC analysis was performed, and the area of ​​the target compound was calculated. A peak was confirmed in the high molecular weight region at 72%. [Chemical Formula 28]

[0079] Comparative Examples 1-2 In Comparative Example 1-1, except that 19.6 g of 3-allyloxy-1,2-propanediol was replaced with 22.2 g of allyl ethylene glycol (molar ratio of unsaturated compound to hydrosiloxy unit = 2.0), a slightly turbid liquid was obtained using the same method as in Comparative Example 1-1. The yield was 43.1 g.1 ¹H-NMR confirmed that it was a compound represented by the formula (201). GPC analysis was performed, and the area of ​​the target compound was calculated, confirming a peak in the high molecular weight region at 85%. [Chemical Formula 29]

[0080] Comparative Examples 1-3 In Comparative Example 1-1, except that 50.0 g of the hydrosiloxane compound shown in Formula (100) above was replaced with 30.0 g of the hydrosiloxane compound shown in Formula (103) above, and 19.6 g of 3-allyloxy-1,2-propanediol was replaced with 114.8 g (molar ratio of unsaturated compound to hydrosiloxane unit = 3.0), the reaction was carried out in the same manner as in Comparative Example 1-1. As a result, gelation occurred during the reaction, and the target product was not obtained.

[0081] Comparative Examples 1-4 In Comparative Example 1-1, except that 50.0 g of the hydrosiloxane compound shown in formula (100) above was replaced with 30.0 g of the hydrosiloxane compound shown in formula (103) above, and 19.6 g of 3-allyloxy-1,2-propanediol was replaced with 97.4 g of allyl ethylene glycol (molar ratio of unsaturated compound to hydrosiloxane unit = 3.0), a white, turbid gel-like solid was obtained using the same method as in Comparative Example 1-1. The yield was 21.4 g. The obtained compound was partially insoluble in the solvent, so only the soluble portion was subjected to GPC determination, and the area of ​​the target compound was calculated. A peak of 54% was confirmed in the high molecular weight region.

[0082] Comparative Examples 1-5 In the method described in Japanese Patent Application Publication No. 2021-073346 (Example 6), except that the hydrosiloxane compound used as a precursor was replaced with the hydrosiloxane compound shown in formula (100) above, the target compound (200P) was synthesized in the same manner to obtain a colorless, slightly turbid liquid. GPC analysis was performed, and the area of ​​the target compound was calculated. A peak of 88% was confirmed in the high molecular weight region.

[0083] As shown in Examples 1-1 to 1-8 and Comparative Examples 1-1 to 1-5, in the addition reaction of unsaturated compounds with tertiary hydroxyl groups at the ends with hydrosiloxanes, the side reaction during the hydrosilylation reaction is suppressed. Therefore, compared with unsaturated compounds containing primary or secondary hydroxyl groups, polysiloxane compounds can be prepared with high purity. Furthermore, the target compound can be prepared even at higher modification rates. In addition, high purity can be synthesized even when the molar ratio of unsaturated compound to hydrosiloxane unit is low, thus reducing the amount of unsaturated compound used and resulting in excellent yield and economy.

[0084] [Examples 2-1 to 2-8, and Comparative Examples 2-1 to 2-3] Example of hydrogel preparation The compounds obtained in Examples 1-1 to 1-8, the compounds obtained in Comparative Examples 1-1 to 1-2 and 1-5, 2-hydroxyethyl methacrylate (HEMA), N,N-dimethylacrylamide (DMA), ethylene glycol dimethacrylate (EGDMA), Irgacure 1173 (IRG1173), and isopropanol (IPA) were mixed according to the compositions and proportions shown in Table 1 and stirred until a homogeneous solution was formed. After stirring, the solution was bubbled with N2 for 5 minutes to fully degas, and then sealed in a polypropylene mold. The solution was cured by UV irradiation using a high-pressure mercury lamp. After curing, the solution was washed sequentially by immersion in isopropanol, a 50% isopropanol aqueous solution, and deionized water for several seconds each to obtain a hydrogel film. The various physical properties of the obtained film were measured according to the methods described below. The results are shown in Table 1.

[0085] [Appearance after curing] Its appearance after curing was observed with the naked eye and evaluated according to the following indicators. A: Uniform and transparent B: Uneven or white and cloudy

[0086] Transparency A hydrated film was prepared by immersing the film in deionized water at 25°C for 48 hours and then wiping off the surface moisture. Its appearance was observed visually and evaluated according to the following indicators. A: Uniform and transparent B: Uneven or white and cloudy

[0087] [Equilibrium moisture content] The film was immersed in deionized water at 25°C for 48 hours, and the surface moisture was wiped off. The mass of the hydrated film was then measured. Next, the hydrated film was dried in an oven at 50°C for 48 hours, and then dried in an oven at 25°C for 24 hours. The mass of the dried film was measured. The equilibrium moisture content was calculated using the following formula. Equilibrium moisture content (%) = 100 × (mass of hydrated film - mass of dried film) / mass of hydrated film

[0088] [Elastic modulus (Young's modulus) and elongation] A hydrated film was prepared by immersing the film in deionized water at 25°C for 48 hours and then wiping off the surface moisture. The Young's modulus of the hydrated film was determined using an Instron 5943. Using a 50 N load cell, measurements were performed on films cut into 0.8 cm × 4.0 cm pieces at an indentation speed of 1 cm / min. A stress-strain curve was plotted with stress on the vertical axis and strain on the horizontal axis, and the initial (linear) slope was calculated as the Young's modulus (MPa). Furthermore, the elongation at fracture was taken as the maximum elongation (%).

[0089] [Table 1]

[0090] As shown in Table 1, the hydrogels of Examples 2-1 to 2-8, which used the polysiloxane compounds of the present invention, exhibit excellent transparency, as well as excellent elastic modulus and maximum elongation. On the other hand, as shown in Table 1, the hydrogels of Comparative Examples 2-1 to 2-3, which used compounds 200, 201, and 200P having primary or secondary hydroxyl groups, had problems with transparency after curing or when moistened; in addition, they had high elastic modulus but low maximum elongation. In other words, the hydrogels using the polysiloxane compounds of the present invention provide medical materials with beneficial hydrophilicity, sufficient strength, and softness.

[0091] [Industrial Applicability] The polysiloxane compounds of the present invention can provide hydrogels with excellent hydrophilicity and strength. The polysiloxane compounds of the present invention are useful as medical materials, such as monomers for the manufacture of ophthalmic devices, contact lenses, intraocular lenses, artificial corneas, and spectacle lenses.

[0092] This instruction manual includes the following methods. [1]: A polysiloxane compound having one or more (meth)acryloyloxy groups in one molecule, characterized in that the side chain end of the polysiloxane compound has a tertiary hydroxyl group. [2]: The polysiloxane compound according to [1] above is characterized in that the polysiloxane compound is a compound represented by the following general formula (1). [Chemical Formula 30] (In the formula, Z is an organic group with 1 to 20 carbon atoms, R is a monovalent hydrocarbon group with 1 to 6 carbon atoms, R' is a monovalent hydrocarbon group with 3 to 20 carbon atoms and a tertiary hydroxyl group at the end, the structural chain of the group may contain ether bonds, n is an integer from 0 to 200, and m is an integer from 3 to 200. However, more than one Z is (meth)acryloyloxy.) [3]: The polysiloxane compound according to [2] above is characterized in that, in the general formula (1), Z is a compound represented by the following general formula (2). [Chemical Formula 31] (In the formula, X is a hydrogen atom or a methyl group, and the dashed line represents a bond with a silicon atom.) [4]: The polysiloxane compound according to [2] or [3] above is characterized in that, in the general formula (1), R is methyl. [5]: The polysiloxane compound according to any one of [2] to [4] above is characterized in that, in the general formula (1), the R' is represented by the following general formula (3) or the following formula (4). [Chemical Formula 32] (In general formula (3), k represents an integer from 0 to 5; in general formula (3) and formula (4), the dashed line represents the bond with silicon atoms.) [6]: The polysiloxane compound according to [5] above is characterized in that k is 0 or 1 in the general formula (3). [7]: A polysiloxane compound according to any one of [2] to [6] above, characterized in that, in the general formula (1), n ​​is an integer from 0 to 100, m is an integer from 3 to 100, and m / (n+m) is 0.15 or more. [8]: The polysiloxane compound according to [7] above is characterized in that, in the general formula (1), m / (n+m) is 0.3 or more. [9]: A polymer, characterized in that it is a polymer of any one of the polysiloxane compounds described in [1] to [8] above.

[10] : The polymer according to [9] above is characterized in that the mass ratio of the polysiloxane compound is 20% or more of the total mass of the polymer.

[11] : A hydrogel characterized in that it comprises the polymer described in [9] or

[10] above.

[12] : A medical material, characterized in that it comprises the polymer described in [9] or

[10] above.

[13] : A method for preparing a polysiloxane compound, characterized in that it comprises: The process of subjecting a compound containing unsaturated groups and tertiary hydroxyl groups at the end to a hydrosilylation reaction with an organohydrogen polysiloxane compound of the following general formula (5) to obtain a polysiloxane compound of the following general formula (1). [Chemical Formula 33] (In the formula, Z are independent organic groups with 1 to 20 carbon atoms, R are independent monovalent hydrocarbon groups with 1 to 6 carbon atoms, n is an integer from 0 to 200, and m is an integer from 3 to 200. However, more than one Z is (meth)acryloyloxy.) [Chemical Formula 34] (In the formula, R' is a monovalent hydrocarbon group with 3 to 20 carbon atoms at the end and a tertiary hydroxyl group. The structural chain of the group may contain ether bonds. Z, R, n, and m are as described above.)

[14] : The method for preparing the polysiloxane compound according to

[13] above is characterized in that, relative to the hydrosiloxane unit, the compound containing unsaturated groups and tertiary hydroxyl groups at the end is set to 1.0 to 3.0 molar equivalents.

[15] : The method for preparing polysiloxane compounds according to

[13] or

[14] above is characterized in that the content of the polysiloxane compound represented by the general formula (1) is set to 90% or more.

[0093] It should be noted that this invention is not limited to the embodiments described above. The embodiments described above are examples, and any structure that has the same technical concept as that described in the claims of this invention and achieves the same effect, regardless of its form, is included within the technical scope of this invention.

Claims

1. A polysiloxane compound containing more than one (meth)acryloyloxy group in one molecule, characterized in that, The side chain terminal of the polysiloxane compound has a tertiary hydroxyl group.

2. The polysiloxane compound according to claim 1, characterized by The polysiloxane compound is a compound represented by the following general formula (1), [Chemical Formula 1] In the formula, Z is independently an organic group having 1 to 20 carbon atoms, R is independently a monovalent hydrocarbon group having 1 to 6 carbon atoms, R' is independently a monovalent hydrocarbon group having 3 to 20 carbon atoms having a tertiary hydroxyl group at the terminal, the structural chain of the group can or can not include an ether bond, n is an integer of 0 to 200, and m is an integer of 3 to 200; however, one or more of Z is a (meth)acryloxy group.

3. The polysiloxane compound according to claim 2, characterized by In the general formula (1), Z is a compound represented by the following general formula (2), [Chemical Formula 2] In the formula, X is a hydrogen atom or a methyl group, and the dotted line indicates a bonding bond to a silicon atom.

4. The polysiloxane compound according to claim 2, characterized by In the general formula (1), R is a methyl group.

5. The polysiloxane compound according to claim 2, characterized by In the general formula (1), R' is a compound represented by the following general formula (3) or the following formula (4), [Chemical Formula 3] In the general formula (3), k represents an integer of 0 to 5; in the general formula (3) and the formula (4), the dotted line indicates a bonding bond to a silicon atom.

6. The polysiloxane compound according to claim 5, characterized by In the general formula (3), k is 0 or 1.

7. The polysiloxane compound according to claim 2, wherein In the general formula (1), n is an integer of 0 to 100, m is an integer of 3 to 100, and m / (n+m) is 0.15 or more.

8. The polysiloxane compound according to claim 7, characterized by In the general formula (1), m / (n+m) is 0.3 or more.

9. A polymer characterized by, It is a polymer of the polysiloxane compound described in any one of claims 1 to 8.

10. The polymer of claim 9, wherein, The mass proportion of the polysiloxane compound is 20 mass% or more of the total mass of the polymer.

11. A hydrogel, characterized in that, It includes the polymer described in claim 9.

12. A medical material, characterized by It includes the polymer described in claim 9.

13. A method for producing a polysiloxane compound, characterized by, The process includes the following steps: A compound having an unsaturated group and a tertiary hydroxyl group at the terminal is subjected to a hydrosilylation reaction with an organohydrogenpolysiloxane compound represented by the following general formula (5), thereby obtaining a polysiloxane compound represented by the following general formula (1), [Chemical Formula 4] In the formula, Z is independently an organic group having 1 to 20 carbon atoms, R is independently a monovalent hydrocarbon group having 1 to 6 carbon atoms, n is an integer of 0 to 200, and m is an integer of 3 to 200; however, one or more of Z is a (meth)acryloxy group, [Chemical Formula 5] In the formula, R' is independently a monovalent hydrocarbon group having 3 to 20 carbon atoms having a tertiary hydroxyl group at the terminal, the structural chain of the group can or can not include an ether bond; Z, R, n, and m are as described above.

14. The method for producing a polysiloxane compound according to claim 13, wherein The compound having an unsaturated group and a tertiary hydroxyl group at the terminal is 1.0 to 3.0 mole equivalents with respect to the hydrosiloxy unit.

15. The method for producing a polysiloxane compound according to claim 13 or 14, wherein The content of the polysiloxane compound represented by the general formula (1) is 90% or more.

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