JP5526845B2 - Silicone monomer - Google Patents
Silicone monomer Download PDFInfo
- Publication number
- JP5526845B2 JP5526845B2 JP2010030826A JP2010030826A JP5526845B2 JP 5526845 B2 JP5526845 B2 JP 5526845B2 JP 2010030826 A JP2010030826 A JP 2010030826A JP 2010030826 A JP2010030826 A JP 2010030826A JP 5526845 B2 JP5526845 B2 JP 5526845B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- monomer
- silicone
- group
- represented
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000178 monomer Substances 0.000 title claims description 52
- 229920001296 polysiloxane Polymers 0.000 title claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 12
- 239000001301 oxygen Substances 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- 230000035699 permeability Effects 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- -1 acrylic ester Chemical class 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000000691 measurement method Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- FYBYQXQHBHTWLP-UHFFFAOYSA-N bis(silyloxysilyloxy)silane Chemical group [SiH3]O[SiH2]O[SiH2]O[SiH2]O[SiH3] FYBYQXQHBHTWLP-UHFFFAOYSA-N 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 125000005401 siloxanyl group Chemical group 0.000 description 3
- STMDPCBYJCIZOD-UHFFFAOYSA-N 2-(2,4-dinitroanilino)-4-methylpentanoic acid Chemical compound CC(C)CC(C(O)=O)NC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O STMDPCBYJCIZOD-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- QABCGOSYZHCPGN-UHFFFAOYSA-N chloro(dimethyl)silicon Chemical compound C[Si](C)Cl QABCGOSYZHCPGN-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- HTDJPCNNEPUOOQ-UHFFFAOYSA-N hexamethylcyclotrisiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O1 HTDJPCNNEPUOOQ-UHFFFAOYSA-N 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000007142 ring opening reaction Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- RSNQKPMXXVDJFG-UHFFFAOYSA-N tetrasiloxane Chemical group [SiH3]O[SiH2]O[SiH2]O[SiH3] RSNQKPMXXVDJFG-UHFFFAOYSA-N 0.000 description 2
- ZQTYRTSKQFQYPQ-UHFFFAOYSA-N trisiloxane Chemical group [SiH3]O[SiH2]O[SiH3] ZQTYRTSKQFQYPQ-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- LBNDGEZENJUBCO-UHFFFAOYSA-N 2-[2-(2-methylprop-2-enoyloxy)ethyl]butanedioic acid Chemical compound CC(=C)C(=O)OCCC(C(O)=O)CC(O)=O LBNDGEZENJUBCO-UHFFFAOYSA-N 0.000 description 1
- BESKSSIEODQWBP-UHFFFAOYSA-N 3-tris(trimethylsilyloxy)silylpropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC[Si](O[Si](C)(C)C)(O[Si](C)(C)C)O[Si](C)(C)C BESKSSIEODQWBP-UHFFFAOYSA-N 0.000 description 1
- 239000005046 Chlorosilane Substances 0.000 description 1
- 102100026735 Coagulation factor VIII Human genes 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- KBJKWYZQIJZAOZ-UHFFFAOYSA-N lithium;oxidosilane Chemical compound [Li+].[SiH3][O-] KBJKWYZQIJZAOZ-UHFFFAOYSA-N 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229940088644 n,n-dimethylacrylamide Drugs 0.000 description 1
- YLGYACDQVQQZSW-UHFFFAOYSA-N n,n-dimethylprop-2-enamide Chemical compound CN(C)C(=O)C=C YLGYACDQVQQZSW-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003961 organosilicon compounds Chemical class 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical compound [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 150000003377 silicon compounds Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Images
Description
本発明は、眼科デバイス、例えば、コンタクトレンズ、眼内レンズ、人工角膜を製造するために利用できる重合可能なシリコーンモノマーに関する。 The present invention relates to polymerizable silicone monomers that can be used to make ophthalmic devices such as contact lenses, intraocular lenses, and artificial corneas.
生体用デバイスを含む種々の物品は、例えば、有機ケイ素化合物含有材料から形成されている。ソフトコンタクトレンズなどの生体用デバイスに有用な有機ケイ素化合物材料の一つに、ケイ素含有ヒドロゲル材料が挙げられる。一般に、ケイ素系の材料は、水よりも高い酸素透過性を有するので、より高い酸素透過性を有する物品が提供できる。
眼科デバイスに用いられる眼用のシリコーンモノマーとして、式（２）で示されるＴＲＩＳ（３−[トリス(トリメチルシロキシ)シリル]プロピルメタクリレート）が知られている（特許文献１）。
該ＴＲＩＳは、眼用レンズ素材として知られたモノマーであるが、疎水性であるためにＨＥＭＡ(２−ヒドロキシエチルメタクリレート)のような親水性モノマーとの相溶性に劣り、これらの親水性モノマーと共重合した場合、透明ポリマーが得られず、レンズ素材として使用できないという欠点がある。
Various articles including a biological device are formed from, for example, an organic silicon compound-containing material. One organosilicon compound material useful for biomedical devices such as soft contact lenses is a silicon-containing hydrogel material. In general, silicon-based materials have higher oxygen permeability than water, and therefore, articles having higher oxygen permeability can be provided.
As an ophthalmic silicone monomer used for an ophthalmic device, TRIS (3- [tris (trimethylsiloxy) silyl] propyl methacrylate) represented by the formula (2) is known (Patent Document 1).
The TRIS is a monomer known as an ophthalmic lens material. However, since it is hydrophobic, it has poor compatibility with hydrophilic monomers such as HEMA (2-hydroxyethyl methacrylate). When copolymerized, there is a disadvantage that a transparent polymer cannot be obtained and cannot be used as a lens material.
そこで、シリコーンハイドロゲルコンタクトレンズ用途に親水性モノマーとシリコーンマクロマーの相溶化を目的として、特許文献２および３において式（３）で表されるモノマーが提案されている。このモノマーは、水酸基を有していることから良好な親水性を発現することが知られている。
しかしながら、モノマー分子内のシロキサニル基は、トリシロキサン構造であり、式（１）で表されるモノマーのテトラシロキサン構造と比較して、シリコーン部が小さい。一般にシリコーンハイドロゲルレンズは、親水相とシリコーン相の共連続相を形成し、透明なゲルを形成するが、トリシロキサン構造では親水部との相溶性が高すぎるため安定な共連続相を形成することが困難である。このため、上記モノマーは、高価なシリコーンマクロマーと併用しなければ十分な酸素透過性を得ることが困難であった。
Thus, for the purpose of compatibilization of a hydrophilic monomer and a silicone macromer for use in silicone hydrogel contact lenses, a monomer represented by the formula (3) is proposed in
However, the siloxanyl group in the monomer molecule has a trisiloxane structure, and has a smaller silicone portion than the tetrasiloxane structure of the monomer represented by the formula (1). Generally, a silicone hydrogel lens forms a co-continuous phase of a hydrophilic phase and a silicone phase to form a transparent gel. However, the trisiloxane structure forms a stable co-continuous phase because the compatibility with the hydrophilic portion is too high. Is difficult. For this reason, it was difficult to obtain sufficient oxygen permeability with the above monomer unless used in combination with an expensive silicone macromer.
特許文献４には、式（４）で表されるシリコーンモノマーが提案されている。該モノマーは、分子内に４級アンモニウム塩基を有しており、さらにテトラシロキサン構造を有することから、親水性モノマーとの相溶性を改善し、かつ式（１）のモノマーと同程度の酸素透過性を得ることが期待されるが、十分な酸素透過性を得るには至っていない。 Patent Document 4 proposes a silicone monomer represented by the formula (4). Since the monomer has a quaternary ammonium base in the molecule and further has a tetrasiloxane structure, the compatibility with the hydrophilic monomer is improved, and oxygen permeation comparable to that of the monomer of formula (1) is achieved. However, it has not yet achieved sufficient oxygen permeability.
特許文献５には、コンタクトレンズの酸素透過性を向上させるために式（５）で表されるモノマーが提案されている。該モノマーは、シリコーン部がペンタシロキサン構造であり、十分な酸素透過性を得ることが期待される。一般に、オリゴエチレングリコールは、そのエーテル結合よりも両末端の水酸基により親水性を得ている。しかし、該モノマーの親水部であるジエチレングリコールの末端水酸基は、エステル結合またはエーテル結合を形成しており、水酸基を有していない。従って、遊離のオリゴエチレングリコールと比較して極性が低いことから十分に親水性を得ることが難しい。オリゴエチレングリコールにより親水性を得るためには、オリゴエチレングリコール構造の繰り返し単位を増加させる必要があるが、反面、モノマー中のシリコーン部の質量は下がる傾向にある。このため、十分な親水性モノマーとの相溶性とレンズの酸素透過性を両立させることが困難である。 Patent Document 5 proposes a monomer represented by the formula (5) in order to improve oxygen permeability of a contact lens. The monomer has a pentasiloxane structure in the silicone portion and is expected to obtain sufficient oxygen permeability. In general, oligoethylene glycol is hydrophilic by its hydroxyl groups at both ends rather than by its ether bond. However, the terminal hydroxyl group of diethylene glycol, which is the hydrophilic part of the monomer, forms an ester bond or an ether bond and does not have a hydroxyl group. Therefore, it is difficult to obtain sufficient hydrophilicity because of its low polarity compared to free oligoethylene glycol. In order to obtain hydrophilicity with oligoethylene glycol, it is necessary to increase the repeating unit of the oligoethylene glycol structure, but on the other hand, the mass of the silicone part in the monomer tends to decrease. For this reason, it is difficult to achieve both compatibility with sufficient hydrophilic monomer and oxygen permeability of the lens.
特許文献６には、式（６）で表されるシリコーンモノマーが提案されている。該モノマーは、ペンタシロキサン構造を有しているため、十分な酸素透過性が期待される。また分子内に水酸基を1つ有することにより、親水性を向上させているが、十分な親水性は得られていない。 Patent Document 6 proposes a silicone monomer represented by the formula (6). Since the monomer has a pentasiloxane structure, sufficient oxygen permeability is expected. Further, the hydrophilicity is improved by having one hydroxyl group in the molecule, but sufficient hydrophilicity is not obtained.
このような事情から、眼科デバイスに用いられる眼用のシリコーンモノマーの分野では、新たな分子構造を持つ親水性を有するシリコーンモノマーであって、製造が容易であり、一日使い捨てレンズのような安価な用途にも使用可能な、また、モノマー内のシロキサニル基が大きいシリコーンモノマーの開発が求められている。 Under these circumstances, in the field of ophthalmic silicone monomers used in ophthalmic devices, hydrophilic silicone monomers having a new molecular structure, which are easy to manufacture, and inexpensive as daily disposable lenses. There is a need to develop a silicone monomer that can be used for various applications and has a large siloxanyl group in the monomer.
本発明の課題は、シリコーン含量が大きく、（メタ）アクリル系モノマー等の重合性モノマーと共重合したとき、高い透明度及び酸素透過率が想定できる、眼に適用するのに好適なシリコーンモノマーを提供することにある。 An object of the present invention is to provide a silicone monomer suitable for application to the eye, which has a high silicone content and can assume high transparency and oxygen permeability when copolymerized with a polymerizable monomer such as a (meth) acrylic monomer. There is to do.
本発明によれば、式（１）で表されるシリコーンモノマーが提供される。
本発明のシリコーンモノマーは、式（１）に示されるとおり、シリコーン含量が高く、また分子内に水酸基と複数のエステル基を有するので、親水性が高く、（メタ）アクリル系モノマー等の重合性モノマーと共重合させた際に、レンズ表面の親水性と酸素透過性を同時に満足すると考えられ、眼科デバイスの原料として有用である。 As shown in the formula (1), the silicone monomer of the present invention has a high silicone content, and since it has a hydroxyl group and a plurality of ester groups in the molecule, it has high hydrophilicity and is polymerizable such as a (meth) acrylic monomer. When copolymerized with a monomer, it is considered that the hydrophilicity and oxygen permeability of the lens surface are satisfied at the same time, which is useful as a raw material for ophthalmic devices.
以下、本発明を更に詳細に説明する。
本発明のシリコーンモノマーは、上記式（１）で表されるように、１つの水酸基と、その近傍に３つの水酸基を有し、且つエステル結合を介して重合性官能基とシロキサニル基が結合している構造を有するので、これを用いた重合体は、高い親水性、透明度及び酸素透過性が期待できる。
式（１）において、Ｒ1は水素原子又はメチル基を示す。Ｒ2は炭素数１〜６の１価の炭化水素基、例えば、メチル基、エチル基、プロピル基、ブチル基、ペンチル基、ヘキシル基を示す。ｎは１〜７の整数を示す。ｎの数字が大きい場合には親水性を得ることが困難となることから、好ましくはｎ＝４である。Ｘは−ＣＨ2−ＣＨ(ＯＨ)ＣＨ2−又は−ＣＨ(ＣＨ2ＯＨ)ＣＨ2−を表す。
Hereinafter, the present invention will be described in more detail.
As represented by the above formula (1), the silicone monomer of the present invention has one hydroxyl group and three hydroxyl groups in the vicinity thereof, and a polymerizable functional group and a siloxanyl group are bonded via an ester bond. Therefore, a polymer using the same can be expected to have high hydrophilicity, transparency and oxygen permeability.
In the formula (1), R 1 represents a hydrogen atom or a methyl group. R 2 represents a monovalent hydrocarbon group having 1 to 6 carbon atoms, such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, or a hexyl group. n shows the integer of 1-7. Since it is difficult to obtain hydrophilicity when the number of n is large, n = 4 is preferable. X represents —CH 2 —CH (OH) CH 2 — or —CH (CH 2 OH) CH 2 —.
本発明のシリコーンモノマーは、例えば、式（７）で表される、分子内に１つの水酸基及び１一つのアリル基を有する（メタ）アクリルエステルと、式（８）で表されるヒドロシリル基を有するシリコーン化合物とを、特開昭５５−１４５６９３号公報等に記載された公知の方法により、白金触媒を用いて反応させることで得られる。 The silicone monomer of the present invention comprises, for example, a (meth) acrylic ester having one hydroxyl group and one allyl group in the molecule represented by formula (7), and a hydrosilyl group represented by formula (8). It is obtained by reacting with a silicone compound having a platinum catalyst by a known method described in JP-A No. 55-145893.
上記反応は、式（７）で示される（メタ）アクリルエステル中に、式（８）で示されるシリコーン化合物を式（７）におけるカルボン酸に対して１０〜１００モル％滴下して、恒温槽中で５０〜１００℃の温度で行なうことが好ましい。この時、溶媒は使用しなくても良いが、トルエン、イソプロパノール等の有機溶媒を用いることが好ましい。 In the above reaction, the silicone compound represented by the formula (8) is dropped into the (meth) acrylic ester represented by the formula (7) in an amount of 10 to 100 mol% with respect to the carboxylic acid in the formula (7), and the thermostatic bath. It is preferable to carry out at a temperature of 50 to 100 ° C. At this time, it is not necessary to use a solvent, but it is preferable to use an organic solvent such as toluene or isopropanol.
式（７）で表される（メタ）アクリルエステルは公知の方法により得られる。具体的には、式（９）で表されるカルボン酸と、式（１０）で表されるアリルグリシジルエーテルとを、塩基触媒存在下で反応させることにより得られる。尚、式（９）中のＲ1は水素原子又はメチル基を示す。 The (meth) acrylic ester represented by the formula (7) is obtained by a known method. Specifically, it can be obtained by reacting the carboxylic acid represented by the formula (9) with the allyl glycidyl ether represented by the formula (10) in the presence of a base catalyst. In addition, R < 1 > in Formula (9) shows a hydrogen atom or a methyl group.
式（８）で表されるシリコーン化合物は、得られる式（１）で表されるシリコーンモノマーの純度に影響するため、高純度品であることが望ましい。式（８）で表されるシリコーン化合物は、公知の技術により得ることができる。例えば、、活性炭を触媒として、ジメチルクロロシランによりヘキサメチルシクロトリシロキサンを開環させ、末端のクロロシランをシラノールと反応させる方法（特開平３−１３５９８５号公報）、リチウムシラノレートによりヘキサメチルシクロトリシロキサンを開環させ、ジメチルクロロシランで反応停止させる方法（特開２００８−２０２０６０号公報）や、環状シロキサンオリゴマーの開環をルイス酸触媒で行なう方法（特開２００８−５３８７６３号公報）により得られる。 Since the silicone compound represented by the formula (8) affects the purity of the silicone monomer represented by the formula (1) to be obtained, it is desirable that the silicone compound is a high purity product. The silicone compound represented by the formula (8) can be obtained by a known technique. For example, a method in which hexamethylcyclotrisiloxane is ring-opened with dimethylchlorosilane using activated carbon as a catalyst and chlorosilane at the terminal is reacted with silanol (Japanese Patent Laid-Open No. 3-135985), and hexamethylcyclotrisiloxane is reacted with lithium silanolate. It can be obtained by a method of ring-opening and stopping the reaction with dimethylchlorosilane (Japanese Patent Laid-Open No. 2008-202060) or a method of ring-opening a cyclic siloxane oligomer with a Lewis acid catalyst (Japanese Patent Laid-Open No. 2008-538863).
本発明のシリコーンモノマーは、眼科デバイスを形成するポリマーの原料として使用することができ、該シリコーンモノマーを用いて眼科デバイスを製造するには、例えば、本発明のシリコーンモノマーと共重合が可能な他のモノマーと混合し、重合させることにより得ることができる。
上記共重合が可能な他のモノマーとしては、例えば、(メタ)アクリロイル基、スチリル基、アリル基、ビニル基などの炭素−炭素不飽和結合を有する公知のモノマーが好ましく挙げられる。重合物表面の十分な親水性を得るため、水酸基、アミド基、両性イオン等の親水基を有するモノマーの使用がより好ましい。具体的には、例えば、２−ヒドロキシエチルメタクリレート、Ｎ，Ｎ−ジメチルアクリルアミド、Ｎ−ビニルピロリドン、２−(メタクリロイルオキシエチル)−２−(トリメチルアンモニオエチル)ホスファートが挙げられる。
本発明のシリコーンモノマーの使用量は、得られる眼科デバイスの表面親水性の改善や、柔軟性をコントロールするために、原料モノマー中１０〜８０質量％が好ましい。
The silicone monomer of the present invention can be used as a raw material of a polymer for forming an ophthalmic device. To produce an ophthalmic device using the silicone monomer, for example, it is possible to copolymerize with the silicone monomer of the present invention. It can obtain by mixing with the monomer of and polymerizing.
Examples of other monomers capable of copolymerization include known monomers having a carbon-carbon unsaturated bond such as a (meth) acryloyl group, a styryl group, an allyl group, and a vinyl group. In order to obtain sufficient hydrophilicity on the polymer surface, it is more preferable to use a monomer having a hydrophilic group such as a hydroxyl group, an amide group or an amphoteric ion. Specific examples include 2-hydroxyethyl methacrylate, N, N-dimethylacrylamide, N-vinylpyrrolidone, 2- (methacryloyloxyethyl) -2- (trimethylammonioethyl) phosphate.
The use amount of the silicone monomer of the present invention is preferably 10 to 80% by mass in the raw material monomer in order to improve the surface hydrophilicity of the obtained ophthalmic device and to control the flexibility.
以下、実施例により本発明を具体的に説明する。
尚、例中の各測定は以下の装置を用いて行った。
１）シリコーンモノマーの純度測定法(ＨＰＬＣ法)
高速液体クロマトグラフィーシステム：東ソー社製ｓｙｓｔｅｍ ＬＣ−８０２０
カラム：Ｃ18（オクタデシル化シリカ）カラム（１５ｍｍ×４．６ｍｍ）
カラム温度：４０℃、検出：ＵＶ（検出波長２６０ｎｍ）、移動相：アセトニトリル／０．０５Ｍ酢酸アンモニウム水溶液（９０／１０、体積／体積）、サンプル濃度： ０．５体積％、
注入量：１００μｌ。
２）1Ｈ−ＮＭＲ測定法
日本電子社製ＪＮＭ−ＡＬ４００
溶媒；ＣＤＣｌ3又はＣＤ3ＯＤ (ＴＭＳ基準)
３）赤外線吸収（ＩＲ）測定法
測定法：液膜法、積算回数：１６回
４）質量測定法（ＬＣ−ＭＳ法）
ＬＣ部：Ｗａｔｅｒｓ社 ２６９５ Ｓｅｐａｒａｔｉｏｎｓ Ｍｏｄｕｌｅ
ＭＳ部；Ｗａｔｅｒｓ ２６９５ Ｑ−ｍｉｃｒｏ
ＬＣ溶離液条件：アセトニトリル／５０ｍＭ酢酸アンモニウム水溶液（９／１）
Hereinafter, the present invention will be described specifically by way of examples.
In addition, each measurement in an example was performed using the following apparatuses.
1) Silicone monomer purity measurement method (HPLC method)
High-performance liquid chromatography system: Tosoh system LC-8020
Column: C 18 (octadecylated silica) column (15 mm × 4.6 mm)
Column temperature: 40 ° C., detection: UV (detection wavelength 260 nm), mobile phase: acetonitrile / 0.05M ammonium acetate aqueous solution (90/10, volume / volume), sample concentration: 0.5% by volume,
Injection volume: 100 μl.
2) 1 H-NMR measurement method JNM-AL400 manufactured by JEOL Ltd.
Solvent; CDCl 3 or CD 3 OD (TMS standard)
3) Infrared absorption (IR) measurement method Measurement method: liquid film method, integration number: 16 times 4) Mass measurement method (LC-MS method)
LC Department: Waters 2695 Separations Module
MS Department; Waters 2695 Q-micro
LC eluent conditions: acetonitrile / 50 mM ammonium acetate aqueous solution (9/1)
合成例：式（１２ａ）または式（１２ｂ）で表される中間体の合成
式（１１）で表される２−メタクリロイルオキシエチルコハク酸（商品名「ライトエステルＨＯ−ＭＳ」、共栄社化学社製）３６２．５２ｇ（１．５８モル）、アリルグリシジルエーテル１２０．０ｇ、ｐ−メトキシフェノール２．４１ｇ、及びトリエチルアミン１１．１５ｇを、１Ｌ四つ口フラスコへ量り取り、磁気攪拌器で内液を攪拌し、溶解した。その後、攪拌しながらオイルバスを使用して８０℃で１０時間反応を行なった。得られた反応液４９１．０ｇを酢酸エチル９８２．７ｇに溶解し、５％重曹水９８２．４ｇを加えて攪拌、分液を行い、未反応のカルボン酸を水相側へ除去した。その後、イオン交換水／メタノール（３／１、重量／重量）約９８２ｇでさらに酢酸エチル相を２回洗浄した後、硫酸マグネシウム１００ｇで酢酸エチル相の脱水を行った。硫酸マグネシウムをろ過した後、溶媒を除去して黄色液体２２５．４ｇを得た。収率は６３％であった。ＨＰＬＣにより純度９６％、また1Ｈ ＮＭＲにより、式（１２ａ）及び式（１２ｂ）で表される中間体であることを確認した。
Synthesis Example: Synthesis of Intermediate Represented by Formula (12a) or Formula (12b) 2-Methacryloyloxyethyl succinic acid represented by formula (11) (trade name “Light Ester HO-MS”, manufactured by Kyoeisha Chemical Co., Ltd. ) 362.52 g (1.58 mol), allyl glycidyl ether 120.0 g, p-methoxyphenol 2.41 g, and triethylamine 11.15 g were weighed into a 1 L four-necked flask, and the internal solution was stirred with a magnetic stirrer. And dissolved. Then, reaction was performed at 80 degreeC for 10 hours using the oil bath, stirring. 491.0 g of the obtained reaction solution was dissolved in 982.7 g of ethyl acetate, 982.4 g of 5% sodium bicarbonate water was added, and the mixture was stirred and separated to remove unreacted carboxylic acid to the aqueous phase side. Thereafter, the ethyl acetate phase was further washed twice with about 982 g of ion-exchanged water / methanol (3/1, weight / weight), and then the ethyl acetate phase was dehydrated with 100 g of magnesium sulfate. After filtering the magnesium sulfate, the solvent was removed to obtain 225.4 g of a yellow liquid. The yield was 63%. It was confirmed to be an intermediate represented by the formula (12a) and the formula (12b) by 96% purity by HPLC and 1 H NMR.
実施例：式（１４）で表されるシリコーンモノマーの合成
５００ｍｌ四つ口フラスコに、合成例で調製した式（１２ａ）及び式（１２ｂ）で表される中間体８３．６ｇ、トルエン８３．６ｇ、及び５％白金担持活性炭（和光純薬工業社製）０．３８５ｇを加えた後、フラスコ内を窒素置換した。オイルバスを使用して反応液を８０℃へ加熱した。次いで、式（１３）で表されるペンタシロキサン５０．０ｇを滴下ロートにて３０分で滴下した。滴下終了後、さらに２．５時間攪拌した後、冷却し、白金担持活性炭をろ別した。続いて、減圧してトルエンを除去して黄色透明液体を得た。この液体１３６．８ｇ、ヘプタン２７３．６ｇ、メタノール２７３．６ｇ、及びイオン交換水６９．９ｇを混合、攪拌し、分液した。さらにイオン交換水／メタノール混合液（１／４、重量／重量）３４１．９ｇで洗浄した。ヘプタン相にメタノール２７３．６ｇと硫酸ナトリウム２３．４ｇとを加え、攪拌し静置して分液させた後、上相を廃棄した。硫酸ナトリウムをろ別した後、脱溶媒して淡黄色透明液体７１．５ｇを得た。収率は７８％であった。
Example: Synthesis of silicone monomer represented by formula (14) In a 500 ml four-necked flask, 83.6 g of intermediates represented by formula (12a) and formula (12b) prepared in the synthesis example and 83.6 g of toluene were prepared. And 0.385 g of 5% platinum-supported activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.), and the inside of the flask was purged with nitrogen. The reaction was heated to 80 ° C. using an oil bath. Next, 50.0 g of pentasiloxane represented by the formula (13) was dropped in a dropping funnel in 30 minutes. After the completion of dropping, the mixture was further stirred for 2.5 hours, then cooled, and platinum-supported activated carbon was filtered off. Subsequently, toluene was removed under reduced pressure to obtain a yellow transparent liquid. 136.8 g of this liquid, 273.6 g of heptane, 273.6 g of methanol, and 69.9 g of ion-exchanged water were mixed, stirred, and separated. Further, it was washed with 341.9 g of an ion exchange water / methanol mixed solution (1/4, weight / weight). Methanol (273.6 g) and sodium sulfate (23.4 g) were added to the heptane phase, stirred and allowed to stand for liquid separation, and then the upper phase was discarded. After sodium sulfate was filtered off, the solvent was removed to obtain 71.5 g of a pale yellow transparent liquid. The yield was 78%.
ＨＰＬＣによる分析の結果、純度８０％であり、1Ｈ ＮＭＲにより、式（１４）で表されるシリコーンモノマーであることを確認した。ＬＣ−ＭＳによる構造特定の結果、並びに1Ｈ ＮＭＲ測定時の５．２ｐｐｍ付近のピークから、分子量７５６の式（１４ａ）で表される化合物と式（１４ｂ）で表される化合物が、約４：１の比で存在する混合物であることがわかった。1Ｈ−ＮＭＲ測定結果を下記及び図１に、ＩＲ測定結果を下記及び図２に示す。 As a result of analysis by HPLC, the purity was 80%, and it was confirmed by 1 H NMR that the silicone monomer was represented by formula (14). From the result of structure identification by LC-MS and the peak around 5.2 ppm at the time of 1 H NMR measurement, the compound represented by formula (14a) and the compound represented by formula (14b) having a molecular weight of 756 were about 4 The mixture was found to be present in a ratio of 1: 1. 1 H-NMR measurement results are shown below and FIG. 1, and IR measurement results are shown below and FIG.
1Ｈ−ＮＭＲ測定結果
ＣＨ2＝Ｃ−：７．２６ｐｐｍ（１Ｈ）、６．１３ｐｐｍ（１Ｈ）、−ＣＨ2−、−ＣＨ−：４．３５ｐｐｍ（４Ｈ）、４．２３〜３．４１ｐｐｍ（７Ｈ）、２．６６ｐｐｍ（４Ｈ）、１．６０ｐｐｍ（２Ｈ）、１，３０ｐｐｍ（４Ｈ）、０．５３ｐｐｍ（４Ｈ）、−ＣＨ3：１．９５ｐｐｍ（３Ｈ）、０．８８ｐｐｍ（３Ｈ）、０．１０ｐｐｍ（３０Ｈ）。
ＩＲ測定結果
３５１０ｃｍ-1、２９６０ｃｍ-1、２９２５ｃｍ-1、２８７５ｃｍ-1、１７４０ｃｍ-1、１６４０ｃｍ-1、１４５５ｃｍ-1、１４１０ｃｍ-1、１３８０ｃｍ-1、１２６０ｃｍ-1、１１５５ｃｍ-1、１０４０ｃｍ-1、８４０ｃｍ-1。
1 H-NMR measurement result CH 2 ═C—: 7.26 ppm (1H), 6.13 ppm (1H), —CH 2 —, —CH—: 4.35 ppm (4H), 4.23 to 3.41 ppm ( 7H), 2.66ppm (4H), 1.60ppm (2H), 1,30ppm (4H), 0.53ppm (4H), - CH 3: 1.95ppm (3H), 0.88ppm (3H), 0 .10 ppm (30 H).
IR measurements 3510cm -1, 2960cm -1, 2925cm -1 , 2875cm -1, 1740cm -1, 1640cm -1, 1455cm -1, 1410cm -1, 1380cm -1, 1260cm -1, 1155cm -1, 1040cm -1 , 840 cm −1 .
本発明のシリコーンモノマーは、コンタクトレンズ等の眼科デバイスの製造に好適に使用される。 The silicone monomer of the present invention is suitably used for the production of ophthalmic devices such as contact lenses.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010030826A JP5526845B2 (en) | 2010-02-16 | 2010-02-16 | Silicone monomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010030826A JP5526845B2 (en) | 2010-02-16 | 2010-02-16 | Silicone monomer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011168495A JP2011168495A (en) | 2011-09-01 |
| JP5526845B2 true JP5526845B2 (en) | 2014-06-18 |
Family
ID=44682998
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010030826A Active JP5526845B2 (en) | 2010-02-16 | 2010-02-16 | Silicone monomer |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5526845B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019018623A1 (en) | 2017-07-19 | 2019-01-24 | The Procter & Gamble Company | Functionalized siloxane polymers and compositions comprising same |
| WO2019018625A1 (en) * | 2017-07-19 | 2019-01-24 | The Procter & Gamble Company | Functionalized siloxane polymers and compositions comprising same |
-
2010
- 2010-02-16 JP JP2010030826A patent/JP5526845B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2011168495A (en) | 2011-09-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8168735B2 (en) | Silicone compound, a process for the preparation thereof and a process for the preparation of an ophthalmic device therefrom | |
| JP5280856B2 (en) | Cationic hydrophilic siloxanyl monomer | |
| JP5795736B2 (en) | Hydrophilic silicone monomers, methods for their preparation and thin films containing them | |
| JP5699931B2 (en) | Silicone monomer | |
| CN110914282A (en) | Siloxane compound and process for producing the same | |
| KR20140137428A (en) | Hydrophilic silicone monomers, process for preparation thereof and thin films containing the same | |
| JP5972090B2 (en) | Method for producing high purity (meth) acryl silicone compound | |
| JP5164452B2 (en) | Fumaric acid derivative and ophthalmic lens using the same | |
| JP2007186512A (en) | Fumaric acid derivative and ophthalmic lens using the same | |
| KR101599913B1 (en) | Noble silicone compound, method for preparing the same and silicone hydrogel contact lens using therewith | |
| JP5526845B2 (en) | Silicone monomer | |
| JP2015096471A (en) | Monomers for ophthalmic device production | |
| US8481608B2 (en) | Silicone monomer | |
| JP2012017285A (en) | Silicone monomer, method of producing the same, monomer composition and polymer | |
| EP2921497B1 (en) | Silicone compound and a use thereof | |
| JP5402934B2 (en) | Silicone monomer, its production method and use | |
| JPH09221530A (en) | Ophthalmic lens material | |
| EP2955208B1 (en) | Silicone compound and a use thereof | |
| WO2013098966A1 (en) | Silicone monomer and method for producing same | |
| JP6305323B2 (en) | Copolymers and ophthalmic devices | |
| JP5387822B2 (en) | Silicone monomer | |
| JP5111837B2 (en) | Method for producing silicone monomer, method for producing intermediate thereof, and molded article thereof | |
| JP2016102158A (en) | Monomer for producing ophthalmologic device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20121226 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140318 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140331 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5526845 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |