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WO2018177329A1 - Composé colorant polymérisable et procédé pour sa préparation et polymère contenant un colorant et utilisation correspondante - Google Patents

Composé colorant polymérisable et procédé pour sa préparation et polymère contenant un colorant et utilisation correspondante Download PDF

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Publication number
WO2018177329A1
WO2018177329A1 PCT/CN2018/080919 CN2018080919W WO2018177329A1 WO 2018177329 A1 WO2018177329 A1 WO 2018177329A1 CN 2018080919 W CN2018080919 W CN 2018080919W WO 2018177329 A1 WO2018177329 A1 WO 2018177329A1
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group
alkyl
polymer
compound
alkoxy
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Chinese (zh)
Inventor
刘敏
康小林
曹立
李德珊
罗贵华
张宏岩
陈佩兴
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Dongguan HEC Tech R&D Co Ltd
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Dongguan HEC Tech R&D Co Ltd
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Priority to CN201880013629.6A priority Critical patent/CN110382628B/zh
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    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B29/00—Monoazo dyes prepared by diazotising and coupling

Definitions

  • the present invention relates to the field of ocular medical devices, and in particular to polymerizable dyes having the ability to absorb ultraviolet and blue light regions.
  • Cataract is caused by turbidity or pigment formation and deposition in the natural lens of the human eye. It changes from transparent to opaque, hindering the entry of light into the eye, leading to a decline in vision or even blindness.
  • IOL intraocular Lens
  • the natural lens has the property of not transmitting ultraviolet light and visible light in the blue region near 400 to 500 nm.
  • the conventional transparent crystal for artificial crystals transmits ultraviolet light and blue region light, resulting in intraocular lens implantation. After the patient has dizziness and blue vision, and the short-wavelength, high-energy blue region light reaches the eye, it will cause serious damage to the retina and cause diseases such as macular degeneration.
  • the present invention aims to solve at least one of the technical problems in the related art at least to some extent.
  • the present invention proposes a novel polymerizable dye compound having a benzophenone skeleton having ultraviolet absorption properties in the molecule and an azobenzene skeleton having absorption properties in a blue region, and thus the dye compound has better properties.
  • Ultraviolet light and blue light interception performance; and the compound has a vinyl polymerizable group can be copolymerized with monomers used in other ophthalmic medical device materials, is difficult to migrate and dissolve in the polymer, and thus is used as an eye part
  • the medical device such as the ultraviolet blue light absorber of the intraocular lens is highly safe to use;
  • the novel polymerizable dye compound of the present invention has an asymmetric alkoxy group as a linking group, so that the compound has excellent solubility and flexibility. Not only is it easier to carry out polymerization with other monomer materials, but the polymer obtained by polymerizing it as a monomer is still expected to maintain flexibility, thereby making handling at the time of surgery easy.
  • novel polymerizable dye compound of the present invention is a compound represented by the following formula (I) or a stereoisomer or tautomer of the compound of the formula (I).
  • R 1 is hydrogen or an alkyl group, preferably hydrogen or methyl
  • R 2 is an alkyl group, preferably methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl;
  • Another aspect of the present invention also provides a polymer comprising the above polymerizable dye compound and thus having a function of blocking ultraviolet light and blue light.
  • the above dye is a polymerizable compound, it can be copolymerized with a monomer used for other ophthalmic medical device materials, and diffusion diffusion does not easily occur in the polymer.
  • Another aspect of the invention also provides the use of the polymer of the invention in the preparation of an ocular medical device.
  • the ocular medical device prepared by using the polymer has the characteristics of low hardness, good flexibility, easy folding, and ability to intercept blue light and ultraviolet light.
  • the above-mentioned ocular medical device includes an intraocular lens, an intraocular lens, a contact lens, a corneal correction, an intracorneal lens, a corneal inlay, a corneal ring, or a glaucoma filter device.
  • the present invention also provides a process for producing the novel polymerizable dye compound and a process for preparing a polymer comprising the dye.
  • Example 1 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A1 obtained in Example 12;
  • Figure 2 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A2 obtained in Example 13;
  • Figure 3 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A3 obtained in Example 14;
  • Example 4 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A4 obtained in Example 15;
  • Figure 5 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A5 obtained in Example 16;
  • Figure 6 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A6 obtained in Example 17;
  • Figure 7 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A7 obtained in Example 18;
  • Figure 8 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A8 obtained in Example 19;
  • Figure 9 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A9 obtained in Example 20;
  • Figure 10 is a graph showing the ultraviolet-visible absorption spectrum of the polymer sheet A10 obtained in Example 21;
  • Fig. 11 is a graph showing the UV-visible absorption spectrum of the polymer sheets A12 obtained in Comparative Example 1 and the polymer sheets A13 and A6 obtained in Comparative Example 2.
  • the dye compound proposed by the present invention has a formula represented by the formula (I), and also includes a stereoisomer or a tautomer conforming to the compound of the formula represented by the formula (I).
  • “Stereoisomer” refers to a compound that has the same chemical structure but differs in the way the atoms or groups are spatially aligned. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotomers), geometric isomers (cis/trans) isomers, and atropisomers and the like.
  • Stereochemical definitions and rules used in the present invention generally follow SP Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stere Stereochemical definitions and rules described in Hemistry of Organic Compounds, John Wiley & Sons, Inc., New York, 1994.
  • optically active compounds Many organic compounds exist in optically active forms, i.e., they have the ability to rotate a plane of plane polarized light.
  • the prefixes D and L, or R and S are used to indicate the absolute configuration of the molecule with respect to one or more of its chiral centers.
  • the prefixes d and l or (+) and (-) are symbols for specifying the rotation of plane polarized light caused by the compound, wherein (-) or l indicates that the compound is left-handed.
  • Compounds prefixed with (+) or d are dextrorotatory.
  • a particular stereoisomer is an enantiomer and a mixture of such isomers is referred to as a mixture of enantiomers.
  • a 50:50 mixture of enantiomers is referred to as a racemic mixture or a racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or process.
  • any asymmetric atom (e.g., carbon, etc.) of the compounds disclosed herein may exist in racemic or enantiomerically enriched form, such as the (R)-, (S)- or (R, S)-configuration presence.
  • each asymmetric atom has at least 50% enantiomeric excess in the (R)- or (S)-configuration, at least 60% enantiomeric excess, at least 70% enantiomeric excess, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess.
  • the compounds of the invention may be one of the possible isomers or mixtures thereof, such as racemates and mixtures of diastereomers (depending on the number of asymmetric carbon atoms) The form exists.
  • Optically active (R)- or (S)-isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the substituent of the cycloalkyl group may have a cis or trans configuration.
  • the resulting mixture of any stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers, for example, by chromatography, depending on the difference in physicochemical properties of the components. Method and / or step crystallization.
  • racemate of any of the resulting end products or intermediates can be resolved into the optical antipodes by methods known to those skilled in the art by known methods, for example, by obtaining the diastereomeric salts thereof. Separation. Racemic products can also be separated by chiral chromatography, such as high performance liquid chromatography (HPLC) using a chiral adsorbent.
  • HPLC high performance liquid chromatography
  • enantiomers can be prepared by asymmetric synthesis, for example, see Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Principles of Asymmetric Synthesis (2nd Ed.
  • tautomer or "tautomeric form” refers to structural isomers having different energies that are interconvertible by a low energy barrier. If tautomerism is possible (as in solution), the chemical equilibrium of the tautomers can be achieved.
  • proton tautomers also known as prototropic tautomers
  • Valence tautomers include interconversions by recombination of some bonding electrons.
  • keto-enol tautomerization is the interconversion of a pentane-2,4-dione and a 4-hydroxypent-3-en-2-one tautomer.
  • Another example of tautomerization is phenol-keto tautomerization.
  • a specific example of phenol-keto tautomerization is the interconversion of pyridin-4-ol and pyridine-4(1H)-one tautomers. All tautomeric forms of the compounds of the invention are within the scope of the invention unless otherwise indicated.
  • the term "ultraviolet light” means visible light having a wavelength in the range of 300 to 400 nm
  • "intercepting ultraviolet light”, "absorbing ultraviolet light” and the like means visible light containing ultraviolet light, a polymerizable dye compound proposed by the present invention or
  • the intensity of the ultraviolet light in the outgoing light on the other side of the material is significantly lower than that of the ultraviolet light in the incident light, even The emitted light does not contain ultraviolet light.
  • blue light means visible light having a wavelength in the range of 400 to 550 nm
  • the terms "intercepting blue light” and “absorbing blue light” refer to a visible light containing blue light, a polymerizable dye compound or polymer proposed by the present invention.
  • the intensity of blue light in the outgoing light on the other side of the material is significantly lower than that of the blue light in the incident light, and is not included in the emitted light. Blu-ray.
  • the “room temperature” in the present invention refers to a temperature which can be attained by subjecting, for example, a reaction liquid, a mixed liquid or the like to an indoor environment for a certain period of time during the synthesis, preparation, and the like without performing additional cooling or heat treatment.
  • the "room temperature” temperature is from about 10 degrees Celsius to about 40 degrees Celsius.
  • “room temperature” refers to a temperature of from about 20 degrees Celsius to about 30 degrees Celsius; in other embodiments, “room temperature” refers to 20 degrees Celsius, 22.5 degrees Celsius, 25 degrees Celsius, 27.5 degrees Celsius, and the like.
  • the term “optional” or “optionally” means that the subsequently described event or situation may, but does not necessarily, occur, and the description includes the case in which the event or situation occurs and in which it does not occur.
  • “optionally substituted alkylene” means that the alkylene group may be unsubstituted by any substituent, or alkyl, halogen, nitro, cyano, aldehyde, amino, alkoxy, haloalkyl, haloalkane Substituted by a substituent such as an oxy group.
  • C 16 alkyl refers particularly to the disclosure independently methyl, ethyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, and C 6 alkyl.
  • alkyl or "alkyl group” denotes a saturated straight or branched chain hydrocarbyl group.
  • the alkyl group contains from 1 to 20 carbon atoms; in another embodiment, the alkyl group contains from 1 to 12 carbon atoms; in another embodiment, the alkyl group contains 1 -8 carbon atoms; in yet another embodiment, the alkyl group contains 1-6 carbon atoms; and in one embodiment, the alkyl group contains 1-3 carbon atoms.
  • alkyl groups include, but are not limited to, methyl (Me, -CH 3 ), ethyl (Et, -CH 2 CH 3 ), n-propyl (n-Pr, -CH 2 CH 2 CH 3 ), isopropyl (i-Pr, -CH(CH 3 ) 2 ), n-butyl (n-Bu, -CH 2 CH 2 CH 2 CH 3 ), isobutyl (i-Bu, -CH 2 CH) (CH 3 ) 2 ), sec-butyl (s-Bu, -CH(CH 3 )CH 2 CH 3 ), tert-butyl (t-Bu, -C(CH 3 ) 3 ), n-pentyl (-CH) 2 CH 2 CH 2 CH 2 CH 3 ), 2-pentyl (-CH(CH 3 )CH 2 CH 2 CH 3 ), 3-pentyl (-CH(CH 2 CH 3 ) 2 ), 2-methyl -2-butyl (-C(CHCH
  • alkoxy denotes an alkyl group attached to the remainder of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described herein. Unless otherwise specified, the alkoxy group contains from 1 to 12 carbon atoms. In one embodiment, the alkoxy group contains from 1 to 6 carbon atoms; in another embodiment, the alkoxy group contains from 1 to 4 carbon atoms; in yet another embodiment, the alkoxy group The group contains 1-3 carbon atoms. The alkoxy group is optionally substituted with one or more substituents described herein.
  • alkoxy groups include, but are not limited to, methoxy (MeO, -OCH 3 ), ethoxy (EtO, -OCH 2 CH 3 ), 1-propoxy (n-PrO, n- Propyloxy, -OCH 2 CH 2 CH 3 ), 2-propoxy (i-PrO, i-propoxy, -OCH(CH 3 ) 2 ), and the like.
  • alkenyl denotes a straight or branched chain hydrocarbon radical having at least one carbon-carbon sp 2 double bond, which includes the positioning of "cis” and “tans", or the positioning of "E” and "Z".
  • the alkenyl group contains 2-20 carbon atoms; in another embodiment, the alkenyl group contains 2-12 carbon atoms; in yet another embodiment, the alkenyl group comprises 2 -8 carbon atoms; also in one embodiment, the alkenyl group contains 2-6 carbon atoms.
  • alkynyl denotes a straight or branched chain hydrocarbon radical having at least one carbon-carbon sp triple bond.
  • the alkynyl group contains 2-20 carbon atoms; in another embodiment, the alkynyl group contains 2-12 carbon atoms; in yet another embodiment, the alkynyl group comprises 2 -8 carbon atoms; also in one embodiment, the alkynyl group contains 2-6 carbon atoms.
  • alkynyl groups include, but are not limited to, ethynyl (-C ⁇ CH), propargyl (-CH 2 C ⁇ CH), 1-propynyl (-C ⁇ C-CH 3 ), and the like. .
  • halogen and halo refer to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).
  • haloalkyl denotes an alkyl, alkenyl or alkoxy group, respectively, substituted by one or more halogen atoms, wherein alkyl, alkenyl and alkoxy
  • the radicals have the meanings described herein, and such examples include, but are not limited to, difluoromethyl, trifluoromethyl, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2 , 2,3,3-tetrafluoropropoxy, and the like.
  • the haloalkyl, haloalkenyl or haloalkoxy group is optionally substituted with one or more substituents described herein.
  • alkoxyalkyl denotes an alkyl group substituted by one or more alkoxy groups, wherein the alkyl group and the alkoxy group have the meanings as described herein, such examples include However, it is not limited to methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl and the like.
  • aryl denotes a monocyclic, bicyclic and tricyclic carbocyclic ring system containing from 6 to 14 ring atoms, or from 6 to 12 ring atoms, or from 6 to 10 ring atoms, wherein at least one ring system is aromatic Of the family, wherein each ring system comprises a ring of 3-7 atoms and one or more attachment points are attached to the remainder of the molecule.
  • the aryl group may include a phenyl group, a naphthyl group, and an anthracenyl group.
  • the substituted group may be fluorine, chlorine, bromine, iodine, cyano, azide, nitro, amino, hydroxy, decyl, alkylamino, alkoxy, alkylthio, Alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl or heteroaryl.
  • aryloxy refers to an optionally substituted aryl group, as defined herein, attached to an oxygen atom and attached to the remainder of the molecule by an oxygen atom, wherein the aryl group Has the meaning as described in the present invention.
  • aryloxy groups include, but are not limited to, phenoxy, halophenoxy, cyano substituted phenoxy, hydroxy substituted phenoxy, and the like.
  • arylalkyl denotes an alkyl group substituted with one or more aryl groups; wherein the alkyl group and the aryl group have the meaning as described herein, and examples of arylalkyl include , but not limited to, benzyl, phenethyl and the like.
  • aryloxyalkyl refers to an alkyl group substituted with one or more aryloxy groups; wherein the aryloxy group and the alkyl group have the meanings as described herein.
  • aryloxyalkyl groups include, but are not limited to, phenoxymethyl, fluorophenoxymethyl (such as (2-fluorophenoxy)methyl, (3-fluorophenoxy)methyl or (4-Fluorophenoxy)methyl), chlorophenoxymethyl, and the like.
  • arylalkoxy means that the alkoxy group is substituted by one or more aryl groups; wherein the alkoxy group and the aryl group have the meanings as described herein.
  • arylalkoxy groups include, but are not limited to, benzyloxy, fluorobenzyloxy, chlorobenzyloxy, cyano substituted benzyloxy, methylsulfonyl substituted benzyloxy, phenylethoxy Base, and so on.
  • novel polymerizable dye compound of the present invention is a compound represented by the following formula (I) or a stereoisomer or tautomer of the compound of the formula (I).
  • R 1 is hydrogen or an alkyl group
  • R 1 is hydrogen or a C 1-6 alkyl group
  • R 1 is hydrogen or a C 1-3 alkyl group
  • R 1 is hydrogen or methyl
  • R 2 is an alkyl group
  • R 2 is a C 1-6 alkyl group
  • R 2 is a C 1-4 alkyl group
  • R 2 is a methyl group or an ethyl group
  • R a , R b and R c is independently hydrogen, hydroxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 6-10 aryl Or a C 6-10 aryl C 1-6 alkyl group;
  • R 3a is particularly preferably hydrogen, hydroxy, methoxy, ethoxy or octyloxy
  • R 3b is particularly preferably hydrogen or a hydroxyl group from the viewpoint of light absorption characteristics
  • R 3c is particularly preferably hydrogen or a hydroxyl group from the viewpoint of light absorption characteristics
  • R 4 is particularly preferably considered from the viewpoint of reaction efficiency in production. It is hydrogen, hydroxy, methyl or ethyl.
  • the benzophenone skeleton is a chromophore that absorbs ultraviolet light
  • the azobenzene skeleton is a chromophore that absorbs blue light, both of which are present in the dye molecule, so that The dye compound of the present invention exhibits good intercepting performance in the ultraviolet light-blue region of 300 to 550 nm.
  • the (meth)acryloyl group is bonded to the azobenzene through an asymmetric ether bond, wherein the (meth)acryloyl group is a reaction site participating in the copolymerization, so that the present invention can be used.
  • the polymeric dye compound can be copolymerized with other polymerizable monomers to greatly reduce the risk of migration of the dye compound in the polymer and improve the safety of the device directly in contact with the human body prepared from the polymer.
  • the asymmetric ether linkage group can increase the solubility of the dye compound, greatly improve the polymerization efficiency when the copolymerization reaction is carried out, and can maintain the flexibility of the polymer molecule obtained after the polymerization, and the polymer is used.
  • the prepared ophthalmic medical device such as intraocular lens has the characteristics of low hardness, flexibility and easy folding, and can intercept blue light and ultraviolet light.
  • the dye compound of the present invention represented by the formula (I) is not particularly limited, but a compound having the following structure is exemplified as a preferred embodiment:
  • the compounds represented by the above formulas (1) to (11) or the stereoisomers or tautomers of the compounds represented by the formulae (1) to (11) have an effect of intercepting blue light and ultraviolet light. Specifically, when the ultraviolet-visible absorption spectrum is measured, the spectral transmittance is almost zero at 400 nm or less, that is, the ultraviolet ray is almost completely blocked, and the rise of the graph sharply occurs around 420 to 500 nm, that is, blue.
  • the light in the color region can be suitably suppressed, and thus can be added as an additive to the raw material of the synthetic ophthalmic medical device, and the above compound does not have optical (refractive index, etc.) and mechanical properties on the ophthalmic medical device.
  • the tensile strength, elongation at break, and elastic modulus, etc. have a negative effect and can therefore be used to prepare flexible ophthalmic medical devices such as foldable intraocular lenses.
  • novel polymerizable dye compound of the present invention can be further combined with other ultraviolet absorbers and/or blue light absorbers in terms of fine-tuning the hue of the ophthalmic medical device and imparting better ultraviolet and blue light absorption properties to the ophthalmic product. Use together.
  • Another aspect of the present invention also provides a process for the preparation of the above novel polymerizable dye compound, which is mainly used as a starting material or an intermediate of the compound represented by the following formula (II) or (III), including a diazotization step and In the esterification step, the synthesis step is not particularly limited, and for example, the dye compound of the present invention can be produced by the following synthesis method.
  • R is hydrogen or a protecting group and R 2 has the definitions described herein.
  • the compound of the above formula (II) or formula (III) is reacted with an acrylic compound or a methacrylic compound or the like to introduce a polymerizable group; then the amino group is exposed, and the amino protecting group can be removed by a deprotection reaction. Or reducing the nitro group to an amino group by a reduction reaction; finally, the above-obtained polymerizable aminoaryl compound is diazotized to obtain a diazonium salt, and then the diazonium salt is subjected to a diazo coupling reaction with a benzophenone compound having a different structure. Thereby, the polymerizable dye compound of the present invention is obtained.
  • the synthesis method 1 is represented by a chemical reaction formula as follows:
  • R represents hydrogen or a protecting group
  • R 5 represents a hydroxyl group or a halogen
  • R 1 , R 2 , R 3a , R 3b , R 3c and R 4 are the same as defined above for the substituent.
  • the compound of the above formula (II) or formula (III) is deprotected by a deprotection reaction, or the nitro group is reduced by a reduction reaction to obtain an aminoaryl compound; the obtained aminoaryl compound is diazotized to obtain The diazonium salt is further subjected to diazo coupling with a benzophenone compound of a different structure to obtain the dye compound of the present invention.
  • the synthesis method 2 is represented by a chemical reaction formula as follows:
  • R represents hydrogen or a protecting group
  • R 5 represents a hydroxyl group or a halogen
  • R 1 , R 2 , R 3a , R 3b , R 3c and R 4 are the same as defined above for the substituent.
  • the amino protecting group R may be tert-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, allyloxycarbonyl, A protecting group such as a tosyl group or a 2-nitrobenzenesulfonyl group.
  • the diazotization reaction, the diazo coupling reaction, the esterification reaction, the nitro reduction reaction, and the deprotection reaction in the above synthesis method can be carried out by a known method.
  • Another aspect of the invention provides a polymer formed by copolymerizing a polymerizable dye compound of the invention with one or more bulk monomers or other polymerizable comonomers.
  • the compound containing the above polymerizable dye thus has an effect of absorbing ultraviolet light and blue light.
  • the above polymerizable dye compound has a group which can participate in polymerization, it can copolymerize with other monomers in the bulk monomer or the raw material of the synthetic polymer, thereby greatly reducing the risk of migration of the dye compound in the polymer.
  • the safety performance of the device directly in contact with the human body prepared from the polymer can be improved.
  • the polymer can be used to prepare an ocular medical device such as an artificial lens, so that the artificial lens can also have the function of intercepting blue light and ultraviolet light, thereby reducing the damage of blue light and ultraviolet light in the visible light to the human eye.
  • bulk monomer specifically refers to the main monomer material used to form the polymer body.
  • the bulk monomer can be polymerized to constitute a main component of the above-mentioned polymer proposed by the present invention, which can be copolymerized with the above polymerizable dye compound in a polymerization reaction.
  • the type of the bulk monomer of the present invention is not particularly limited, and in some embodiments of the present invention, the bulk monomer is an acrylate or methacrylate monomer.
  • the bulk monomer may include at least one of 2-phenylethyl acrylate, 2-phenylethyl methacrylate, and ethoxyethyl methacrylate.
  • the bulk monomer is a vinyl-based monomer, which may include, but is not limited to, at least one of the following monomers: styrene, 4-butylstyrene, styrene, vinyl acetate, 4-ethoxymethylstyrene, 4-hexyloxymethylstyrene, 4-hexyloxyethylstyrene, vinyl ether, n-butyl vinyl ether, isobutyl vinyl ether, uncle Butyl vinyl ether, cyclohexene vinyl ether, butanediol divinyl ether, N-vinyl caprolactam, dodecyl vinyl ether, octadecyl vinyl ether, divinyl glyco
  • the bulk monomer is an allyl monomer, which may include, but is not limited to, at least one of the following monomers: methyl crotonate, ethyl crotonate, benzene crotonate. Ethyl ester, propylene acetate, propylene propionate, propylene butyrate, propylene valerate, propylene hexanoate, 3-phenyl-2-propenyl butyrate.
  • the above bulk monomer has better optical and mechanical properties, and can further improve the performance of the polymer.
  • the "other polymerizable monomer” specifically means other polymerizable monomers constituting the polymer raw material proposed by the present invention in addition to the bulk monomer, such as a polymerizable ultraviolet absorber, a blue light absorber, Crosslinking agent, initiator, and the like.
  • At least one of a crosslinking agent, an initiator, and an ultraviolet absorber may be further included.
  • the above-mentioned crosslinking agent, initiator, and bulk monomer, and the above-mentioned dye compound which absorbs the ultraviolet/blue light region are mixed, and the polymer proposed by the present invention is formed by polymerization.
  • the crosslinking agent may include, but is not limited to, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, 1,3-propanediol. Dimethacrylate, 1,6-hexanediol dimethacrylate, 1,3-butanediol dimethacrylate, 1,4-butanediol dimethacrylate, 1,4-butyl Diol diacrylate, trimethylolpropane trimethacrylate, 1,5-bis(methacryloyloxy) 2,2,3,3,4,4-hexafluorohexane, 1,6 Bis(acryloyloxy) 2,2,3,3,4,4,5,5-octafluorohexane and pentaerythritol tetraacrylate.
  • the initiator may include, but is not limited to, benzoyl peroxide, t-butyl hydroperoxide, cumyl hydroperoxide, bis(4-tert-butylcyclohexyl)peroxydicarbonate. , azobisisobutyronitrile and azobis(2,4-dimethylvaleronitrile).
  • benzoyl peroxide t-butyl hydroperoxide
  • cumyl hydroperoxide bis(4-tert-butylcyclohexyl)peroxydicarbonate.
  • azobisisobutyronitrile and azobis(2,4-dimethylvaleronitrile) azobisisobutyronitrile
  • a known polymerizable ultraviolet absorber (a substance mainly absorbing an ultraviolet ray portion), a blue absorbing agent (a substance mainly absorbing light in a blue region), or a material may be further used in combination. At the same time, it absorbs substances in the ultraviolet/blue light region.
  • Polymeric UV absorbers may include, but are not limited to, 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, 2-[3-(2H-benzo) Triazol-2-yl)-4-hydroxyphenyl]ethyl 2-methacrylate, 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-propenyl) Phenol, 2-(5-chloro-2H-benzo[d][1,2,3]triazole)-4-methyl-6-(2-allyl)phenol, 4-allyl- 2-(5-chloro-2H-benzo[d][1,2,3]triazole)-6-methoxyphenol, 2-(5-chloro-2H-1,2,3-benzo[ d][1,2,3]
  • the blue light absorber may include, but is not limited to, an azo system, an anthracene system, a nitro group, a phthalocyanine system, or the like, and these may be used alone or in combination of two or more.
  • the material having the ultraviolet/blue light absorption region at the same time may include, but is not limited to, benzophenone or 2-hydroxy-4-(p-styrene) such as 2,4-dihydroxy-3(p-styreneazo)benzophenone.
  • a benzoic acid such as benzoic acid phenyl group or the like absorbs a dye compound in an ultraviolet/blue light region. They may be used singly or in combination of two or more.
  • suitable comonomers may be selected to impart various functional properties to the polymers proposed herein.
  • a silicon-containing monomer such as a silicon-containing (meth) acrylate or a silicon-containing styrene derivative or a fluorine-containing monomer may be selected.
  • Alkyl (meth) acrylates or the like may be used.
  • an alkyl (meth) acrylate or a styrene-containing styrene derivative (meth) acrylate or the like may be selected.
  • a polymer is provided to have a function of preventing lipid contamination.
  • hydrophilicity is imparted to the polymer of the present invention
  • the comonomer only (meth)acrylic acid hydroxyesters, (meth)acrylamides, (meth)acrylic acid aminoalkyl esters, (A) are selected.
  • the monomer having a hydrophilic group such as an acrylate or an N-ethyl lactam may be used.
  • the polymer of the present invention can be used as a lens having a high refractive index. material.
  • the polymerizable dye compound proposed by the present invention has excellent absorption characteristics in ultraviolet light (wavelength below 400 nm) and blue light region (wavelength: 400 nm to 500 nm), and the polymer proposed by the present invention contains a dye compound having the above properties. Therefore, the polymer of the present invention also has excellent absorption properties in the ultraviolet light and blue light regions.
  • the ultraviolet visible absorption spectrum of the polymer proposed by the present invention is as shown in FIGS. 1 to 10, and is below 400 nm. The light transmittance reaches 0%, almost completely blocking the ultraviolet light, and the sharp rise of the graph appears around 420-500 nm, which weakens the intensity of the blue region to some extent.
  • the dye compound proposed by the present invention has a polymerizable group and can be copolymerized with other monomers in the polymer, so that the phenomenon that the dye compound migrates and elutes from the polymer does not occur.
  • the dye compound proposed by the present invention has an asymmetric ether bond as a linking group, which greatly increases the solubility of the dye compound, greatly improves the polymerization efficiency when the copolymerization reaction is carried out, and enables the polymer obtained after the polymerization. Molecules remain fairly compliant and are suitable for use in eye medical devices such as intraocular lenses for specific functions.
  • the invention provides a method of making the polymers described above.
  • the method comprises: subjecting the raw material mixture to a gradient heating or a photocuring treatment to obtain a polymer.
  • the raw material mixture contains the bulk monomer described above and a dye compound that absorbs ultraviolet light and blue light.
  • the specific types of the bulk monomer and the dye compound have been described in detail above and will not be described herein.
  • the ratio of the bulk monomer and the dye compound is also not particularly limited. One skilled in the art can make adjustments to the above ratios based on the requirements for the specific physicochemical properties of the particular polymer being prepared, as well as the particular type of bulk monomer, dye compound selected.
  • At least one of a crosslinking agent, an initiator, and an ultraviolet absorber may be further included in the raw material mixture.
  • the method has simple operation steps, short production cycle, and the obtained polymer has ideal physical and chemical properties (such as optical and mechanical properties and intercepting blue light function).
  • the gradient heat treatment described above may include:
  • the first reaction stage The first reaction stage:
  • the raw material mixture is heated to 40 to 102 degrees Celsius for reaction, preferably at 40 to 70 degrees Celsius, and the reaction time may be from 1 to 48 hours.
  • the reaction at a lower temperature prevents the reaction rate from being too fast, which is advantageous for forming a sample having a uniform appearance, thereby improving the performance of the polymer.
  • the raw material mixture passing through the first reaction stage is heated to 40 to 140 ° C for the reaction, preferably at 80 to 120 ° C, and the reaction time may be from 1 to 48 hours.
  • the reaction time may be from 1 to 48 hours.
  • the invention provides an ocular medical device comprising the polymer as set forth above in the present invention.
  • the ocular medical device has all of the features and advantages of the foregoing polymers, and will not be described again.
  • the ocular medical device has ideal mechanical and optical properties, and can intercept ultraviolet light and blue light components in visible light, thereby reducing damage of ultraviolet rays and blue light to human eyes and the like; the ocular medical device has better
  • the safety performance is because the ultraviolet/blue light absorbing dye compound in the polymer proposed by the present invention is not easily migrating and diffusing in the polymer, thereby preventing the dye compound from coming into direct contact with the human body.
  • the eye medical treatment also has the characteristics of low hardness, good flexibility, and easy folding, which makes handling at the time of surgery easier.
  • the above-mentioned ocular medical device may be an intraocular lens, an intraocular lens, a contact lens, a corneal correction, an intracorneal lens, a corneal inlay, a corneal ring or a glaucoma filter device.
  • the polymer of the present invention can be used as a material for an artificial crystal.
  • the polymer of the present invention can be molded by a known method.
  • a polymerization method can be carried out in a suitable mold or container to obtain a rod-shaped, block-shaped, or plate-shaped polymer, and then processed into a desired shape by a processing method such as cutting, polishing, or laser processing. After the polymer is formed into a shape or a polymerization reaction in a mold corresponding to the desired shape, finer processing is performed as needed.
  • the structure is dominant.
  • Step 3 Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-methoxypropan-2-ol
  • Step 4 Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-methoxypropan-2-yl methacrylate
  • Step 5 Synthesis of the compound 1-(4-aminophenoxy)-3-methoxypropan-2-yl methacrylate
  • Step 6 Synthesis of the compound 1-(4-((3-benzoyl-4-hydroxyphenyl)diazenyl)phenoxy)-3-methoxypropan-2-yl methacrylate
  • Step 1 Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-methoxyprop-2-yl acrylate
  • Step 2 Synthesis of the compound 1-(4-aminophenoxy)-3-methoxyprop-2-yl acrylate
  • Step 3 Compound 1-(4-((5-benzoyl-4-hydroxy-2-methoxyphenyl)diazenyl)phenoxy)-3-methoxypropan-2-ylacrylic acid Ester synthesis
  • Step 3 Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-ethoxypropan-2-ol
  • Step 4 Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-ethoxypropan-2-yl methacrylate
  • Step 5 Synthesis of the compound 1-(4-aminophenoxy)-3-ethoxypropan-2-yl methacrylate
  • Step 6 Compound 1-(4-((5-benzoyl-4-hydroxy-2-methoxyphenyl)diazenyl)phenoxy)-3-ethoxyprop-2-ylmethyl Synthesis of acrylate
  • the mold was placed in an oven at 60 ° C for 3 hours, and the oven was elevated to 100 ° C and continued to maintain. After 3 hours, a transparent and elastic polymer was obtained, and the obtained material was ultrasonically washed in absolute ethanol and vacuum dried at 60 ° C for 24 hours.
  • Test method The spectral transmittance of the material in the range of 200 nm to 800 nm light wave was measured by an Agilent Cary 60 ultraviolet-visible spectrophotometer at room temperature.
  • Figure 11 is a graph showing the spectral transmittance of the polymer A12 prepared in Comparative Example 1, the polymer A13 prepared in Comparative Example 2, and the polymer A6 prepared in Example 17.
  • the polymer A12 prepared in Comparative Example 1 without any other ultraviolet absorber and the dye compound proposed by the present invention has a strong transmittance at 310 nm and a permeation at 370 nm.
  • the ratio is higher than 90%, and there is no absorption of ultraviolet light and blue light; and the polymer A13 prepared by adding the conventional ultraviolet absorber but not adding the dye compound proposed by the present invention has a spectrum of ultraviolet rays of 400 nm or less.
  • the polymers A1 to A10 prepared in Examples 12 to 21 of the dye compound of the present invention can completely absorb ultraviolet light of 400 nm or less, and can also significantly reduce the spectral transmission of wavelengths of 400 to 500 nm.
  • the blue light has a good absorption rate, and in the visible light range, the maximum value of the spectral transmittance is higher than 91%. Therefore, the polymer added with the dye compound proposed by the invention can not only intercept the ultraviolet light better. Blue light, and can maintain good transparency.
  • the dye compounds prepared in the above Examples 1 to 10 were weighed in five portions for each dye, 20 mg each, and then 2-phenylethyl acrylate 80 mg, 180 mg, 380 mg, 780 mg, and 1980 mg were sequentially added to obtain a mass fraction of 20%. , 10%, 5.0%, 2.5%, 1.0% of five different concentrations of the solution, the dissolution of the dye compounds prepared in the above Examples 1 to 10 in the monomer was observed. The mixture of each group was sonicated for one minute, and shaken. If a clear transparent solution was obtained, it was considered to be soluble, a liquid-solid homogeneous mixed phase was obtained, or a solid precipitate was still insoluble. The test results are shown in Table 1.
  • the description of the terms “one embodiment”, “another embodiment”, “an example” or the like means that a specific feature, structure, material or characteristic described in connection with the embodiment or example is included in the present invention. At least one embodiment or example.
  • the schematic representation of the above terms is not necessarily directed to the same embodiment or example.
  • the particular features, structures, materials, or characteristics described may be combined in a suitable manner in any one or more embodiments or examples.
  • various embodiments or examples described in the specification, as well as features of various embodiments or examples may be combined and combined.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)

Abstract

L'invention concerne un nouveau composé colorant polymérisable et un procédé pour sa préparation et un polymère comprenant le composé colorant, un procédé pour sa préparation et l'utilisation correspondante. La présente invention concerne le domaine des dispositifs médicaux oculaires. Le composé colorant décrit ci-dessus est un composé polymérisable, ne migre ni ne se diffuse facilement dans un polymère et présente d'excellentes propriétés d'absorption en ce qui concerne les rayons ultraviolets et la lumière bleue et un polymère polymérisé avec l'implication dudit composé convient pour des dispositifs médicaux oculaires.
PCT/CN2018/080919 2017-03-29 2018-03-28 Composé colorant polymérisable et procédé pour sa préparation et polymère contenant un colorant et utilisation correspondante Ceased WO2018177329A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114075122A (zh) * 2020-08-17 2022-02-22 康小林 一种亲水性偶氮化合物及其用途

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113307742B (zh) * 2021-05-19 2022-05-17 南京工业大学 一种蓝光吸光材料及其制备方法和应用、防蓝光镜片
CN113527567B (zh) * 2021-07-26 2023-01-24 康小林 疏水性无闪光点高折光率眼科聚合物材料

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104284942A (zh) * 2012-04-27 2015-01-14 兴和株式会社 稳定的人工晶体用聚合性紫外线吸收色素
WO2015064674A1 (fr) * 2013-10-30 2015-05-07 興和株式会社 Procédé de fabrication d'un colorant absorbant les uv polymérisable
WO2015064675A1 (fr) * 2013-10-30 2015-05-07 興和株式会社 Procédé de fabrication d'un colorant polymérisable absorbant les rayons uv
JP2015084891A (ja) * 2013-10-30 2015-05-07 興和株式会社 眼内レンズ用重合性紫外線吸収色素

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2753067B2 (ja) * 1988-09-16 1998-05-18 株式会社メニコン 眼用レンズ用重合性紫外線吸収性色素並びにそれを用いた眼用レンズ材料
MX341789B (es) * 2012-05-25 2016-09-02 Bausch & Lomb Lente de hidrogel de silicona con bloqueo de ultravioleta (uv) completamente polimerizada.

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104284942A (zh) * 2012-04-27 2015-01-14 兴和株式会社 稳定的人工晶体用聚合性紫外线吸收色素
WO2015064674A1 (fr) * 2013-10-30 2015-05-07 興和株式会社 Procédé de fabrication d'un colorant absorbant les uv polymérisable
WO2015064675A1 (fr) * 2013-10-30 2015-05-07 興和株式会社 Procédé de fabrication d'un colorant polymérisable absorbant les rayons uv
JP2015084891A (ja) * 2013-10-30 2015-05-07 興和株式会社 眼内レンズ用重合性紫外線吸収色素

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114075122A (zh) * 2020-08-17 2022-02-22 康小林 一种亲水性偶氮化合物及其用途
CN114075122B (zh) * 2020-08-17 2024-01-02 康小林 一种亲水性偶氮化合物及其用途

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