JP6037454B2 - Monomers for ophthalmic device manufacturing - Google Patents

Description

  The present invention relates to monomers for producing ophthalmic devices such as contact lenses, intraocular lenses, and artificial corneas (hereinafter also referred to as “ophthalmic monomers”) and methods for producing the same. Specifically, a monomer having a silicone portion having a predetermined molecular weight, copolymerized with a polymerizable monomer such as a (meth) acrylic monomer, and giving a polymer suitable for application to the eye having high transparency and oxygen permeability. It relates to the manufacturing method.

The following silicone compounds are known as ophthalmic monomers.

  The above TRIS (3- [tris (trimethylsiloxy) silyl] propyl methacrylate) has poor compatibility with hydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA), and when copolymerized with these hydrophilic monomers, There is a disadvantage that a transparent polymer cannot be obtained. On the other hand, the SiGMA is excellent in compatibility with a hydrophilic monomer such as HEMA, and the copolymer is characterized by relatively high oxygen permeability and high hydrophilicity. However, in recent years, ophthalmic polymers have been required to have higher oxygen permeability in order to enable long-term continuous wear, and polymers obtained from SiGMA have insufficient oxygen permeability.

ＳｉＧＭＡにおいてビス(トリメチルシロキシ)メチルシリル部分をＳｉ部分とし、全体に占めるＳｉ部分の質量割合を求めると５２％となる。一方、上記式(ａ)において、トリス(トリメチルシロキシ)シリル部分をＳｉ部分とし、全体に占めるＳｉ部分の質量割合を求めると６０％となる。即ち、上記式（ａ）の化合物は、Ｓｉ部分の質量割合が多い。その為、得られる眼科デバイスに高い酸素透過性をもたらすことができる。 In order to solve this problem, Patent Document 1 describes a compound represented by the following formula (a) (hereinafter referred to as “(a)”).

In SiGMA, the bis (trimethylsiloxy) methylsilyl moiety is defined as the Si moiety, and the mass ratio of the Si moiety in the whole is 52%. On the other hand, in the above formula (a), the tris (trimethylsiloxy) silyl moiety is the Si moiety, and the mass ratio of the Si moiety in the whole is 60%. That is, the compound of the formula (a) has a large mass ratio of the Si portion. Therefore, high oxygen permeability can be brought to the obtained ophthalmic device.

  However, when the mass ratio of the Si portion is increased in order to increase the oxygen permeability, there is a problem that the strength of the copolymer polymer is lowered because the molecular weight per polymerizable group is increased. Patent Document 2 describes that the compound represented by the above formula (a) is prepared by reacting an epoxy precursor with methacrylic acid, but this reaction has many side reactions and is a copolymer polymer obtained. There was also a problem that the physical properties of the camera were greatly blurred.

  As described in the background art section of Patent Document 5, tetramer silicone or more is preferable from the viewpoint of oxygen permeability, and in order to achieve both oxygen permeability and strength of the copolymer, the tetramer is preferable. Silicones and pentameric silicone are considered preferred. Therefore, development of a method for obtaining a silicone monomer having a tetramer or higher silicone with high purity is required.

該方法で得られた生成物は、２−ヒドロキシエチルメタクリレート等の親水性モノマーと混合した時に白濁する場合がある。さらに、クロロシランによる該シリコーン鎖の末端封鎖率が高くない。 In Patent Document 3, a chlorosilane having a (meth) acryl group such as 3- (2-methacryloyloxyethoxy) propyldimethylchlorosilane is reacted with anion-polymerized cyclic siloxane using lithium trialkylsilanolate as an initiator. A method for preparing a silicone compound represented by the following formula (b) is described.

The product obtained by this method may become cloudy when mixed with a hydrophilic monomer such as 2-hydroxyethyl methacrylate. Furthermore, the terminal blocking rate of the silicone chain by chlorosilane is not high.

（ｒは３以上の整数）
しかし、上記方法では、エステル化率が不十分で末端封鎖率が低く、また、シリコーンの重合度に分布ができる。 Patent Document 4 describes a method for preparing a silicone compound represented by the following formula (c) by esterification or transesterification of one-terminal hydroxyl group-containing organopolysiloxane and (meth) acrylic acid (ester).

(R is an integer of 3 or more)
However, in the above method, the esterification rate is insufficient, the end-capping rate is low, and the degree of polymerization of silicone can be distributed.

(ここでｍは３〜１０の整数のうちの一つ、ｎは１または２のうちの一つ、Ｒ¹は炭素数１〜４のアルキル基のうちの一つ、Ｒ^２は水素及びメチル基のうちの一つである) Patent Document 5 describes a method for preparing a silicone represented by the following formula by esterification of a one-terminal hydroxyl group-containing organopolysiloxane and a (meth) acrylic acid halide. Patent Document 5 is capable of producing a high-purity silicone monomer containing more than 95% by weight of one kind of silicone compound represented by the following formula (d) and having specific m, n, R ¹ and R ² by the method. Is described.

(Where m is one of integers from 3 to 10, n is one of 1 or 2, R ¹ is one of alkyl groups having 1 to 4 carbon atoms, R ² is hydrogen and methyl. One of the groups)

Patent Document 6 describes an ophthalmic lens using a monomer represented by the following formula and a polymer containing the monomer as a polymerization component.

JP 2007-186709 A Japanese Patent Laid-Open No. 2007-1918 JP 59-78236 A JP 2001-55446 A Japanese Patent No. 4646152 Japanese Patent No. 4882136

  However, the monomer compound described in Patent Document 5 has a hydrophilic group structure limited to an ethylene oxide group. Therefore, the degree of hydrophilicity cannot be adjusted, and the compatibility with the (meth) acrylic monomer to be used in combination, particularly the fluorine substituent-containing (meth) acrylic monomer that imparts stain resistance may be poor. . In addition, the polymer obtained from the monomer may have insufficient mechanical strength.

  The monomer compound described in Patent Document 6 also has a hydrophilic group structure of ethylene oxide-ethylene oxide structure. Since the hydrophilic group structure is ethylene oxide-ethylene oxide structure, it is highly hydrophilic, so it is compatible with the (meth) acrylic monomer used in combination, particularly the fluorine-containing group-containing (meth) acrylic monomer that imparts stain resistance. The solubility may be poor.

  Patent Document 6 also describes a monomer having a urethane bond (Claim 3). However, in the monomer described in Patent Document 6, the structure of the siloxane portion is tris (trimethylsiloxy) silyl, bis (trimethylsiloxy) methylsilyl, pentamethyldisiloxy and the like and does not have a chain siloxane structure. The monomer having such a structure may have a low oxygen permeability when used as a polymer or may have poor shape recoverability.

  Therefore, the present invention contains a predetermined number of silicon atoms and has good compatibility with (meth) acrylic monomers, particularly fluorine-containing group-containing (meth) acrylic monomers that impart stain resistance, To provide a silicone compound that is suitable as an ophthalmic monomer and that can provide a polymer having excellent mechanical strength, and to provide a method for producing the compound, in particular, a method for producing a compound having high purity. With the goal.

  As a result of intensive studies to solve the above problems, the present inventors have found that the compound represented by the following formula (1) or (2) has good compatibility with the (meth) acrylic monomer and is colorless and transparent. It was found that a polymer excellent in mechanical strength was obtained, and the present invention was achieved.

(式（１）及び（２）において、ｍは２〜１０の整数であり、ｎは１または２であり、Ｒ¹は炭素数１〜４のアルキル基であり、Ｒ^２は互いに独立に、水素原子又はメチル基である) That is, this invention provides the compound represented by following formula (1) or (2), and the manufacturing method of this compound.

(In the formulas (1) and (2), m is an integer of 2 to 10, n is 1 or 2, R ¹ is an alkyl group having 1 to 4 carbon atoms, and R ² are independently of each other. (It is a hydrogen atom or a methyl group.)

  The compound represented by the formula (1) or (2) of the present invention (hereinafter sometimes referred to as a monomer) has good compatibility with a polymerizable monomer such as a (meth) acrylic monomer. Copolymerization gives a colorless and transparent polymer. In particular, the polymer has good compatibility with a fluorine-substituted group-containing (meth) acrylic monomer that imparts stain resistance, and is excellent in hydrophilicity and stain resistance. Moreover, since it has a predetermined amount of silicon atoms, it has high oxygen permeability. Furthermore, since the spacer portion has a urethane bond, a hydrogen bond is formed between the polymers, and a polymer having excellent mechanical strength is obtained. Furthermore, according to the production method of the present invention, a compound containing a single compound having a specific structure with high purity is provided. Therefore, the compound and the production method of the present invention are suitable for producing an ophthalmic device.

  The compound of the present invention is represented by the above formula (1) or (2). When the compound has a urethane bond, a hydrogen bond is formed between the obtained polymers, and a polymer having excellent mechanical strength can be obtained. Furthermore, the compound of the present invention has an ethylene oxide-propylene oxide structure (formula (1)) or a propylene oxide-ethylene oxide structure (formula (2)) at a portion connecting the urethane bond and the siloxane structure (hereinafter referred to as a spacer portion). ). When the spacer part structure is ethylene oxide only or ethylene oxide-ethylene oxide structure, it has high hydrophilicity. Therefore, it is suitable for (meth) acrylic monomers, especially fluorine-containing group-containing (meth) acrylic monomers that give stain resistance. The compatibility becomes worse. In addition, when the structure of the spacer portion is a propylene oxide-propylene oxide structure, the compatibility with the fluorine-containing group-containing (meth) acrylic monomer is good, but the hydrophobicity of the polymer becomes too high, so the hydrophilicity is impaired. It is. In addition, when the structure of the spacer portion is a polyalkylene oxide structure, the strength of the obtained copolymer is lowered, which is not preferable.

In the above formulas (1) and (2), m is an integer of 2 to 10, preferably 3 to 7, and most preferably 3. When m is less than the lower limit, the oxygen permeability is low. On the other hand, if m exceeds the upper limit, the hydrophilicity becomes low. When m is in the above range, the compound has a chain siloxane structure having a desired silicon principle amount, so that the oxygen permeability or shape recoverability when a polymer is obtained is improved. R ¹ is an alkyl group having 1 to 4 carbon atoms, preferably a butyl group, and R ² is hydrogen or a methyl group.

  In the above formulas (1) and (2), n is 1 or 2. It is preferably 2 in terms of imparting hydrophilicity to the compound. If n exceeds the above upper limit, the hydrophilicity is too high to achieve high purity by washing with water, and it is difficult to obtain a (meth) acrylic group-containing isocyanate compound as a raw material.

The present invention can provide a compound which is represented by the above formula (1) or (2) and contains one kind of compound having a specific structure with high purity by the method described later. One type having a specific structure means one kind of compound having a specific one of m, n, R ¹ and R ² . High purity means that the compound constitutes more than 95% by mass, preferably 99% by mass or more of the total mass of the compound. In the present invention, the purity is determined by gas chromatography (hereinafter referred to as “GC”) analysis. Detailed conditions will be described later. When the compound has the high purity, a transparent polymer can be obtained without causing turbidity when mixed with a non-silicone monomer such as 2-hydroxyethyl methacrylate.

In particular, a compound in which m is 3 is preferable, and a compound in which m is 3 and R ¹ is a butyl group is more preferable. In Formula (1) or Formula (2), when R ¹ is a butyl group, m is 3, and n is 2, the molecular weight of the compound is 691, and the dimethylpolysiloxane chain relative to the total mass of the compound The mass proportion of the part is about 51%. That is, since the compound has a high Si content, the resulting copolymer has high oxygen permeability.

  The present invention further provides a method for producing the compound represented by the above formula (1) or (2).

（ｍ、Ｒ^１及びＲ^２は上述のとおりである）
下記式（５）で表される(メタ)アクリル基含有イソシアネート化合物を

(ｎ及びＲ^２は上述のとおりである)
反応させる工程を含む。該反応は、式（３）または式（４）のポリオルガノシロキサンの、無溶媒下あるいはトルエンまたはヘキサン等の溶液中に、式（５）の(メタ)アクリル基含有イソシアネート化合物を、徐々に添加して、水浴等で冷却しながら０〜５０℃の温度で行なうことが好ましい。 The production method of the present invention comprises a silicone compound represented by the following formula (3) or formula (4):

(M, R ¹ and R ² are as described above)
A (meth) acrylic group-containing isocyanate compound represented by the following formula (5)

(n and R ² are as described above)
A step of reacting. In the reaction, the (meth) acrylic group-containing isocyanate compound of the formula (5) is gradually added to the solution of the polyorganosiloxane of the formula (3) or the formula (4) without solvent or in a solution such as toluene or hexane. And it is preferable to carry out at the temperature of 0-50 degreeC, cooling with a water bath etc.

  The amount of the (meth) acrylic group-containing isocyanate compound of the formula (5) is 1 to 3 mol, preferably 1.05 to 2 mol with respect to 1 mol of the polyorganosiloxane of the formula (3) or the formula (4). If it is less than the said lower limit, the polyorganosiloxane of Formula (3) or Formula (4) will remain as an unreacted substance, and high purity cannot be achieved. Moreover, it is economically disadvantageous if the upper limit is exceeded.

  In the reaction, a catalyst may be used as necessary. The catalyst may be a generally used isocyanate reaction catalyst, preferably a tin compound or an amine catalyst. As the tin catalyst, a carboxylate compound of tin (II) is preferable from the viewpoint of catalytic activity, and as the amine catalyst, a tertiary amine such as triethylamine, tributylamine, N-ethyldiisopropylamine is preferable. The amount of the catalyst used is 0.001 to 0.1% by mass, more preferably 0.005 to 0.05% by mass, based on the polyorganosiloxane of formula (3) or formula (4). When used exceeding the upper limit, the effect is saturated and uneconomical. When it is less than the lower limit, the catalytic effect is insufficient, the reaction rate is low, and the productivity is lowered.

  In a preferred embodiment of the method of the present invention, the presence or absence of a residual silicone compound (formula (3) or formula (4)) is monitored by GC measurement. After confirming the disappearance of the peak, an alcohol such as methanol or ethanol is added to the reaction product. The remaining isocyanate of the (meth) acrylic group-containing isocyanate compound is inactivated. An organic solvent and water are added and stirred, and then allowed to stand to separate into an organic layer and an aqueous layer. After the organic layer is washed several times with water, the solvent in the organic layer is stripped, so that side reactions are hardly observed in the reaction, so that a highly pure silicone monomer of the formula (1) or formula (2) is obtained.

（ｍ及びＲ^１は上述のとおりである）
下記式（７）または式（８）で表される化合物（以下、アリルエーテル化合物という）を付加反応させて製造することができる。

（Ｒ^２は上述のとおりである） The silicone compound represented by the above formula (3) or (4) is a polyorganohydrogensiloxane represented by the following formula (6):

(M and R ¹ are as described above)
It can be produced by subjecting a compound represented by the following formula (7) or formula (8) (hereinafter referred to as an allyl ether compound) to an addition reaction.

(R ² is as described above)

  The addition reaction may be performed according to a conventionally known method. For example, the reaction is performed in the presence of an addition reaction catalyst such as a platinum group compound. At that time, a solvent may be used. For example, aliphatic solvents such as hexane and toluene, and aromatic solvents such as ethanol and IPA can be preferably used. The allyl ether compound is used in an amount of 1.2 mol or more, preferably 1.5 mol or more per mol of the polyorganohydrogensiloxane.

Preferred examples of the allyl ether compound represented by the above formulas (7) and (8) include compounds represented by the following formulas.

  In a preferred embodiment, for example, an allyl ether compound is diluted with a solvent as necessary, and a platinum-based hydrosilylation catalyst is added thereto. The kind in particular of platinum-type hydrosilylation catalyst is not restrict | limited, A conventionally well-known thing can be used. Furthermore, polyorganohydrogensiloxane is dropped and reacted at room temperature or higher. After completion of the dropwise addition, after aging under heating, the presence or absence of the starting polyorganohydrogensiloxane is confirmed by the disappearance of the peak in, for example, GC measurement. By confirming the reaction end point by GC measurement, since the polyorganohydrogensiloxane does not remain in the product, a high-purity silicone compound can be obtained. The above reaction may be carried out in a lump.

  After completion of the addition reaction, excess allyl ether compound is removed from the reaction solution. Examples of the method include stripping under reduced pressure, or a method in which the reaction product is washed with ion-exchanged water or sodium nitrate water to extract and remove the allyl ether compound into the aqueous layer. At this time, in order to obtain good two-layer separation, it is preferable to use an appropriate amount of a solvent such as toluene or hexane. In particular, by stripping the solvent from the organic layer under reduced pressure, the silicone compound of the above formula (3) or formula (4) can be obtained with a high purity of more than 95% by mass, and more than about 97% by mass. In order to increase the purity, distillation may be performed a plurality of times.

The polyorganohydrogensiloxane represented by the above formula (6) can be produced by a known method. For example, in the formula (6), when R ¹ is a butyl group and m = 3, first, BuMe ₂ SiOLi is synthesized using BuLi, and this is used as an initiator to ring-open hexamethylcyclotrisiloxane. It can be made by stopping the reaction with dimethylchlorosilane. This is purified by distillation to obtain a product with a purity of 99% or more. For example, in formula (6), the boiling point of monobutyldecamethylhydropentasiloxane in which R ¹ is a butyl group and m is 3 is 110 ° C./2 mmHg. This may be distilled after addition reaction with ethylene propylene glycol mono (meth) allyl ether represented by formula (7) or formula (8). However, since the addition reaction product has a higher boiling point, the addition reaction The silicone compound of the above formula (3) or formula (4) can also be obtained with high purity by increasing the purity by distillation in the stage before making it.

  Further, the hydroxyl group in ethylene propylene glycol mono (meth) allyl ether is converted to a silyl ester with a silylating agent such as hexamethyldisilazane, and the silyl ester is hydrolyzed after the above addition reaction to obtain the formula (3) or (4) The silicone compound may be obtained.

  The compound of the present invention has good compatibility with polymerizable monomers such as (meth) acrylic monomers. Therefore, a colorless and transparent polymer can be obtained by copolymerizing with the polymerizable monomer. In particular, a polymer having good compatibility with a fluorine substituent-containing (meth) acrylic monomer that imparts stain resistance, and excellent hydrophilicity and stain resistance can be provided.

  Other polymerizable monomers include, for example, (meth) acrylic acid, methyl (meth) acrylate, ethyl (meth) acrylate, (poly) ethylene glycol dimethacrylate, polyalkylene glycol mono (meth) acrylate, polyalkylene glycol monoalkyl Acrylic monomers such as ether (meth) acrylate, trifluoroethyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2,3-dihydroxypropyl (meth) acrylate; N, N-dimethylacrylamide, N, N- Acrylic acid derivatives such as diethyl acrylamide, N-acryloyl morpholine, N-methyl (meth) acrylamide; other unsaturated aliphatic or aromatic compounds such as crotonic acid, cinnamic acid, vinyl benzoic acid; and polymerizable groups Yes silicone compounds. These may be used alone or in combination of two or more.

  Copolymerization of the compound of the present invention with the other polymerizable monomer may be performed by a conventionally known method. For example, it can be carried out using a known polymerization initiator such as a thermal polymerization initiator or a photopolymerization initiator. As polymerization initiators, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, azobisisobutyronitrile, azobisdimethylvaleronitrile, benzoyl peroxide, tert-butyl hydroperoxide, cumene hydro For example, peroxide. These polymerization initiators can be used alone or in admixture of two or more. The compounding quantity of a polymerization initiator is 0.001-2 mass parts with respect to a total of 100 mass parts of a polymerization component, Preferably it is 0.01-1 mass part.

  The polymer containing the compound of the present invention as a polymerization component is suitable for producing ophthalmic devices such as contact lenses, intraocular lenses, and artificial corneas. The manufacturing method of the ophthalmic device using the polymer is not particularly limited, and may be a conventional ophthalmic device manufacturing method. For example, when forming into a lens shape such as a contact lens or an intraocular lens, a cutting method or a mold method can be used.

EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated in detail, this invention is not restrict | limited to the following Example. In the following Examples, the viscosity was measured using a Canon Fenceke viscometer, and the specific gravity was measured using a buoyancy meter. The refractive index was measured using a digital refractometer RX-5000 (manufactured by Atago Co., Ltd.). ¹ H-NMR analysis was performed using JNM-ECP500 (manufactured by JEOL Ltd.) and deuterated chloroform as a measurement solvent.
In the following, the purity of the compound is determined by gas chromatography (GC) measurement under the following conditions.
Gas chromatography (GC) measurement conditions Gas chromatograph: Agilent detector: FID, temperature 300 ° C
Capillary column: HP-5MS (0.25 mm × 30 m × 0.25 μm) from J & W
Temperature increase program: 50 ° C (5 minutes) → 10 ° C / minute → 250 ° C (hold)
Inlet temperature: 250 ° C
Carrier gas: Helium (1.0 ml / min)
Split ratio: 50: 1
Injection volume: 1 μl

及びトルエン２５０ｇを、攪拌機、ジムロート、温度計、及び滴下ロートを付けた２リットルフラスコに仕込み、７０℃まで昇温した。塩化白金酸アルカリ中和物ビニルシロキサン錯体触媒トルエン溶液(白金含有量０.５％)０.７ｇを前記フラスコ中に添加した後、滴下ロートを用いて、１−ブチル−９−ヒドロ−１，１，３，３，５，５，７，７，９，９−デカメチルペンタシロキサン２７６ｇ(０.６７ｍｏｌ)を４時間かけて前記フラスコ中へ滴下した。内温は８５℃まで上昇した。１００℃で２時間熟成後に反応物をＧＣで分析したところ、原料モノブチルデカメチルヒドロペンタシロキサンのピークが消失し、反応が完結したことを示した。反応物に４００ｇのイオン交換水を加え、攪拌しながら水洗し、静置して相分離させ、過剰のアリルエーテル化合物を含む水層を除去した。次いで、４００ｇのイオン交換水で２回水洗し、有機層のトルエンを減圧ストリップして、無色透明である、下記式（１０）で表されるシリコーン化合物３７９．４ｇ(０．６６ｍｏｌ、収率９９％)を得た。ＧＣ測定による該シリコーン化合物の純度は９９.０質量％だった。

[Example 1]
320.0 g (2.0 mol) of an allyl ether compound represented by the following formula (9),

And 250 g of toluene were charged into a 2 liter flask equipped with a stirrer, a Dim funnel, a thermometer, and a dropping funnel, and the temperature was raised to 70 ° C. After 0.7 g of an alkali chloroplatinic acid neutralized vinylsiloxane complex catalyst toluene solution (platinum content 0.5%) was added to the flask, 1-butyl-9-hydro-1, 276 g (0.67 mol) of 1,3,3,5,5,7,7,9,9-decamethylpentasiloxane was dropped into the flask over 4 hours. The internal temperature rose to 85 ° C. When the reaction product was analyzed by GC after aging at 100 ° C. for 2 hours, the peak of the raw material monobutyldecamethylhydropentasiloxane disappeared, indicating that the reaction was complete. 400 g of ion-exchanged water was added to the reaction product, washed with stirring, and allowed to stand for phase separation, and the aqueous layer containing excess allyl ether compound was removed. Subsequently, it was washed twice with 400 g of ion-exchanged water, and the toluene in the organic layer was stripped under reduced pressure to be colorless and transparent, 379.4 g (0.66 mol, yield 99) of the silicone compound represented by the following formula (10). %). The purity of the silicone compound as measured by GC was 99.0% by mass.

143 g (0.25 mol) of the silicone compound represented by the above formula (10), 0.01 g (0.01% by mass) of dioctyltin oxide, 0.01 g of ionol, and 0.01 g of 4-methoxyphenol were added to a stirrer, Dimroth, A 1 liter flask equipped with a thermometer and a dropping funnel was charged, and 40.3 g (0.26 mol) of a (meth) acrylic group-containing isocyanate compound of the following formula (11) was added dropwise over 1 hour. The internal temperature rose from 20 ° C to 40 ° C. Aging was performed at 40 ° C. while monitoring the peak of the silicone compound by GC. After 4 hours, it was confirmed that the peak of the silicone compound was below the detection limit by GC, and 4.0 g (0.125 mol) of methanol was added to the reaction solution. Furthermore, 180 g of hexane and 180 g of ion exchange water were added and washed with water. After standing and separating to cut the aqueous layer, it was further washed twice with water. The organic layer was stripped under reduced pressure with hexane or the like as a solvent to obtain 163 g of a colorless transparent liquid product. It was confirmed by ¹ H-NMR analysis that it was a monomer represented by the following formula (12) (0.22 mol, yield 88%). The purity of the monomer measured by GC was 96.2%, the viscosity was 43.4 mm ² / s (25 ° C.), the specific gravity was 0.994 (25 ° C.), and the refractive index was 1.4390.

[Example 2]
Instead of 40.3 g (0.26 mol) of the (meth) acrylic group-containing isocyanate compound of the above formula (11) in Example 1, 30.9 g (0.26 mol) of the (meth) acrylic group-containing isocyanate compound of the following formula (13) Example 1 was repeated except that 185.0 g of a colorless transparent liquid product was obtained. It was confirmed by ¹ H-NMR analysis that it was a monomer represented by the following formula (14) (0.24 mol, yield 96%). The monomer was found to have a purity of 96.3%, a viscosity of 38.3 mm ² / s (25 ° C.), a specific gravity of 1.001 (25 ° C.), and a refractive index of 1.4399.

[Example 3]
Example 1 was repeated except that 320.0 g (2.0 mol) of the following formula (15) allyl ether was used instead of 320.0 g of the allyl ether of formula (9) in Example 1, and represented by the following formula (16). There were obtained 379.0 g (0.66 mol, 99% yield) of the silicone compound. The purity of the silicone compound as measured by GC was 99.1% by mass.

［実施例４］
上記式（１１）の(メタ)アクリル基含有イソシアネート化合物４０．３ｇ(０.２６ｍｏｌ)の替わりに式（１３）の(メタ)アクリル基含有イソシアネート化合物３０．９ｇ(０.２６ｍｏｌ) を使用した以外は実施例３を繰り返し、無色透明液体の生成物１７７．３ｇを得た。^１Ｈ-ＮＭＲ分析にて下記式（１８）で表されるモノマーであることが確認された(０．２３ｍｏｌ、収率９１％)。該モノマーのＧＣ測定による純度は９５．７％であり、粘度は３７．９ｍｍ^２／ｓ（２５℃）、比重１．００４（２５℃）、屈折率１．４３９７であった。

Example 1 was repeated except that 143 g (0.25 mol) of the silicone compound of the above formula (16) was used instead of 143 g of the silicone compound represented by the above formula (10) synthesized in Example 1, to produce a colorless transparent liquid 167.2 g of product was obtained. It was confirmed by ¹ H-NMR analysis that it was a monomer represented by the following formula (17) (0.23 mol, yield 94%). The purity of the monomer measured by GC was 96.0%, the viscosity was 44.5 mm ² / s (25 ° C.), the specific gravity was 0.995 (25 ° C.), and the refractive index was 1.4394.

[Example 4]
Other than using 30.9 g (0.26 mol) of the (meth) acrylic group-containing isocyanate compound of the formula (13) instead of 40.3 g (0.26 mol) of the (meth) acrylic group-containing isocyanate compound of the above formula (11). Example 3 was repeated to obtain 177.3 g of a colorless transparent liquid product. It was confirmed by ¹ H-NMR analysis that it was a monomer represented by the following formula (18) (0.23 mol, yield 91%). The purity of the monomer measured by GC was 95.7%, the viscosity was 37.9 mm ² / s (25 ° C.), the specific gravity was 1.004 (25 ° C.), and the refractive index was 1.4397.

[Comparative Example 1]
76.5 g (0.75 mol) of ethylene glycol monoallyl ether and 100 g of toluene were charged into a 1 liter flask equipped with a stirrer, a Dim funnel, a thermometer, and a dropping funnel, and the temperature was raised to 70 ° C. After adding 0.38 g of a chloroplatinic acid alkali neutralized vinylsiloxane complex catalyst toluene solution (platinum content 0.5%) to the flask, using a dropping funnel, 1-butyl-9-hydro-1, 1,3,3,5,5,7,7,9,9-decamethylpentasiloxane (206 g, 0.5 mol) was dropped into the flask over 1 hour. The internal temperature rose to 85 ° C. When the reaction product was analyzed by GC after aging at 100 ° C. for 1 hour, the peak of the raw material monobutyldecamethylhydropentasiloxane disappeared, indicating that the reaction was complete. 200 g of ion-exchanged water was added to the reaction product, washed with stirring, allowed to stand and phase-separated, and the aqueous layer containing excess ethylene glycol monoallyl ether was removed. Similarly, it was washed twice with 200 g ion-exchanged water, and toluene in the organic layer was stripped under reduced pressure to obtain 242 g (yield 94%) of a silicone compound which is a colorless transparent liquid and represented by the following formula (19). The purity of the silicone compound as measured by GC was 99.4% by mass.

A 2-liter flask equipped with 205.6 g (0.4 mol) of the silicone compound of the above formula (19), 50.6 g (0.5 mol) of a dehydrochlorination agent, and 500 g of hexane, and equipped with a stirrer, a Dim funnel, a thermometer and a dropping funnel. The mixture of methacrylic acid chloride 48.1g (0.46mol) and hexane 50g was dripped over 1 hour, cooling a flask in a water bath. The internal temperature rose from 20 ° C to 30 ° C. The water bath was removed and the mixture was aged at room temperature while monitoring the peak of the silicone compound with GC. After 10 hours, since the peak of the silicone compound was below the detection limit by GC, 500 g of ion-exchanged water was added to the reaction solution and washed with water. After standing and separating to cut the aqueous layer, it was further washed twice with water. The organic layer was stripped under reduced pressure with hexane or the like as a solvent to obtain 206 g of a colorless transparent liquid product. ¹ H-NMR analysis confirmed that it was a methacrylic monomer represented by the following formula (20) (yield 89%). The purity of the silicone compound by GC measurement is 98.5%, the viscosity is 5.9 mm ² / s (25 ° C.), the specific gravity is 0.944 (25 ° C.), and the refractive index is 1.4260. there were.

[Comparative Example 2]
Comparative Example 1 was repeated except that 109.5 g (0.75 mol) of diethylene glycol monoallyl ether was used in place of 76.5 g of ethylene glycol monoallyl ether in Comparative Example 1. After completion of the reaction, it was washed with 200 g of ion-exchanged water. As a result, the water was changed to 5% sodium nitrate water. Toluene in the organic layer was stripped under reduced pressure to obtain 240 g (yield 87%) of a silicone compound represented by the following formula (21). The purity of the compound determined by GC measurement was 99.1% by mass.

Example 1 was repeated except that 139.5 g (0.25 mol) of the silicone compound of the formula (21) was used instead of 143 g (0.25 mol) of the silicone compound of the formula (10) in Example 1. 164 g of a clear liquid product was obtained. ¹ H-NMR analysis confirmed that it was a methacrylic monomer represented by the following formula (22) (0.23 mol, yield 92%). The purity of the monomer determined by GC measurement was 96.3% by mass, the viscosity was 34.5 mm ² / s (25 ° C.), the specific gravity was 0.990 (25 ° C.), and the refractive index was 1.4373. .

[Comparative Example 3]
In Comparative Example 2, instead of 40.3 g (0.26 mol) of the (meth) acrylic group-containing isocyanate compound of the above formula (11), 30.9 g of (meth) acrylic group-containing isocyanate compound of the above formula (13) Comparative Example 2 was repeated except that 26 mol) was used to obtain 174.1 g of a colorless transparent liquid product. ¹ H-NMR analysis confirmed that it was a methacrylic monomer represented by the following formula (23) (0.23 mol, yield 92%). The purity of the monomer determined by GC measurement was 96.3% by mass, the viscosity was 30.8 mm ² / s (25 ° C.), the specific gravity was 0.999 (25 ° C.), and the refractive index was 1.4371. .

[Comparative Example 4]
Comparative Example 1 was repeated except that 130.5 g (0.75 mol) of dipropylene glycol monoallyl ether was used in place of 76.5 g of ethylene glycol monoallyl ether of Comparative Example 1, which was a colorless transparent liquid having the following formula (24 ) Was obtained 254.9 g (0.43 mol, yield 87%). The purity of the monomer determined by GC measurement was 99.2% by mass.

In Comparative Example 2, Comparative Example 2 was used except that 146.5 g (0.25 mol) of the silicone compound represented by the above formula (24) was used instead of 139.5 g of the silicone carbinol represented by the above formula (21). Repeatedly, 163.0 g of a colorless transparent liquid product was obtained. ¹ H-NMR analysis confirmed that it was a methacrylic monomer represented by the following formula (25) (0.22 mol, yield 88%). The purity of the monomer determined by GC measurement was 96.6% by mass, the viscosity was 35.3 mm ² / s (25 ° C.), the specific gravity was 1.003 (25 ° C.), and the refractive index was 1.4392. .

[Comparative Example 5]
In Comparative Example 4, instead of 40.3 g (0.26 mol) of the (meth) acrylic group-containing isocyanate compound of the above formula (11), 30.9 g (0.26 mol) of the (meth) acrylic group-containing isocyanate compound of the above formula (13). Comparative Example 4 was repeated except that 180.5 g of a colorless transparent liquid product was obtained. ¹ H-NMR analysis confirmed that it was a methacrylic monomer represented by the following formula (26) (0.23 mol, yield 92%). The purity of the monomer determined by GC measurement was 96.3% by mass, the viscosity was 31.1 mm ² / s (25 ° C.), the specific gravity was 1.005 (25 ° C.), and the refractive index was 1.4401. .

[Evaluation test]
The following evaluation test was done about the monomer obtained in Examples 1-4 and Comparative Examples 1-5. The results are shown in Table 1.

(1) Monomer compatible monomer (60 parts by mass), N, N-dimethylacrylamide (35 parts by mass), triethylene glycol dimethacrylate (1 part by mass), trifluoroethyl (meth) acrylate (5 parts by mass), Darocur 1173 (Ciba Specialty Chemicals, 0.5 parts by mass) was mixed and stirred. The appearance of the obtained mixture was visually observed. A mixture having good compatibility between the monomer and another compound becomes colorless and transparent, but a mixture having poor compatibility causes turbidity.

(2) Appearance of film (polymer) The mixture prepared in (1) above was degassed under an argon atmosphere. The mixed solution was poured into a mold sandwiching two quartz glass plates and irradiated with an ultra-high pressure mercury lamp for 1 hour to obtain a film having a thickness of about 0.3 mm. The appearance of the film was visually observed.

(3) Water wettability (surface hydrophilicity) of the film (polymer)
The contact angle meter CA-D type (manufactured by Kyowa Interface Science Co., Ltd.) was used for the film produced in (2) above, and the water contact angle was measured by a liquid appropriate method.

(4) Contamination resistance of film (polymer) The film produced in (2) above was immersed in a 37 ° C. phosphate buffer solution (PBS (−)) for 24 hours. Each film before immersion and after immersion for 24 hours was incubated at 37 ° C. ± 2 ° C. for 8 hours in a known artificial lipid solution. Thereafter, it was rinsed with PBS (−) and immersed in a 0.1% Sudan black-sesame oil solution. The case where no difference was observed in the dyeing state before and after the immersion was indicated as ◯, and the case where the difference was observed was indicated as ×.

(5) Mechanical strength Two films were prepared according to (2) above, and after wiping off the surface moisture of one of them, the film was immersed in a 37 ° C. phosphate buffer solution (PBS (1)) for 24 hours. Each of the films before dipping in PBS (1) and after dipping for 24 hours was cut into a dumbbell shape having a width of 2.0 mm, the upper and lower ends of the test sample were sandwiched with jigs, and the breaking strength and breaking elongation were maintained at a constant speed. Was measured using a break tester AGS-50NJ (manufactured by Shimadzu Corporation). In the case where the breaking strength and breaking elongation change within 10% before and after being immersed in PBS (one), ○ is marked when a decrease exceeding 10% is observed.

  The monomer compound of the present invention has good compatibility with other (meth) acrylic monomers, and can provide a colorless and transparent polymer. Moreover, since it is well compatible with the fluorine substituent-containing (meth) acrylic monomer, a polymer having excellent hydrophilicity and stain resistance can be provided. Furthermore, the polymer which was excellent in mechanical strength is given by having a urethane bond. In contrast, a polymer obtained from a monomer having a structure in which a urethane bond and a siloxane structure are linked to each other has an ethylene oxide structure or an ethylene oxide-ethylene oxide structure has poor compatibility with a (meth) acrylic monomer and is transparent. Cannot be obtained. In addition, a polymer obtained from a monomer having a propylene oxide-propylene oxide structure is inferior in water wettability (surface hydrophilicity).

  The monomer of the present invention is obtained by copolymerizing with a polymerizable monomer to provide a polymer having oxygen permeability, colorless and transparent and excellent in mechanical strength, in particular, a polymer excellent in hydrophilicity and stain resistance. Can be given. Moreover, according to the production method of the present invention, a monomer containing one kind of compound having a specific structure with high purity can be provided. Therefore, the monomer and manufacturing method of the present invention are useful for manufacturing ophthalmic devices such as contact lens materials, intraocular lens materials, and artificial cornea materials.

Claims (7)

A compound represented by the following formula (1) or formula (2).

(In the formulas (1) and (2), m is an integer of 2 to 10, n is 1 or 2, R ¹ is an alkyl group having 1 to 4 carbon atoms, and R ² are independently of each other. A hydrogen atom or a methyl group) m is 3, A compound according to claim 1 wherein. A polymer obtained by polymerizing the compound according to claim 1 or 2 and another polymerizable compound. An ophthalmic device comprising the polymer according to claim 3 . A method for producing a compound represented by the following formula (1) or formula (2),

(In the formulas (1) and (2), m is an integer of 2 to 10, n is 1 or 2, R ¹ is an alkyl group having 1 to 4 carbon atoms, and R ² are independently of each other. A hydrogen atom or a methyl group)
A silicone compound represented by the following formula (3) or formula (4):

(M, R ¹ and R ² are as described above)
(Meth) acrylic group-containing isocyanate compound represented by the following formula (5)

(N and R ² are as described above)
The manufacturing method including the process made to react. A polyorganohydrogensiloxane represented by the following formula (6) with a silicone compound represented by the above formula (3) or formula (4);

(M and R ¹ are as described above)
A compound represented by the following formula (7) or formula (8):

(R ² is as described above)
The production method according to claim 5 , wherein the production is performed by addition reaction. The production method according to claim 6 , wherein m is 3. 7.