WO2008038721A1

WO2008038721A1 - Ocular lens

Info

Publication number: WO2008038721A1
Application number: PCT/JP2007/068831
Authority: WO
Inventors: Kazuhiko Fujisawa; Tsutomu Goshima; Masataka Nakamura
Original assignee: Toray Industries, Inc.
Priority date: 2006-09-29
Filing date: 2007-09-27
Publication date: 2008-04-03
Also published as: JP2008083649A; JP4899757B2

Abstract

Disclosed is an ocular lens having excellent antibacterial properties which do not deteriorate even when the ocular lens is rinsed with water. The ocular lens is characterized in that it is obtained by dispersing a polymer compound (A), which contains a monomer unit having an ammonium group in a molecule, into a hydrogel (B).

Description

Specification

Ophthalmic lens

Technical field

The present invention relates to an ophthalmic lens, and the ophthalmic lens is particularly preferably used for a contact lens, an intraocular lens, an artificial cornea, and the like.

Background art

[0002] One of the problems seen in contact lens wearers is the problem of bacterial infection. As one of the countermeasures, there is known a method for suppressing the adhesion of bacteria during contact lens storage by including an antibacterial component in the contact lens cleaning / preserving solution (for example, patents). Reference 1). However, with this method, the antibacterial component can be washed and washed even if it is removed from the washing solution and lightly washed with water. Has a problem that it is difficult to obtain a sufficient effect. Patent Document 1: Special Table 2006—509532

Disclosure of the invention

Problems to be solved by the invention

[0003] It is an object of the present invention to provide an ophthalmic lens that is excellent in antibacterial properties and does not deteriorate even when washed with water.

Means for solving the problem

In order to achieve the above object, the present invention has the following configuration. That is,

(1) An ophthalmic lens comprising: a polymer compound (A) having a monomer unit having an ammoium group in the molecule, dispersed in a gel or gel (B).

(2) When the number of alcoholic hydroxyl groups in the ophthalmic lens is represented by OH and the number of ammonium nitrogen by N, the N / OH ratio is 0.001 to 0.5. Ophthalmic lens.

(3) The ophthalmic lens according to (1) or (2) above, wherein the hide-mouth gel (B) is a silicone-hide mouth gel containing a silicone component at 20% by weight or more.

(4) The ophthalmic lens according to the above (3), wherein 50% or more of the number of key atoms in the silicone component in the hide mouth gel (B) is a key atom of the polar silicone component .

(5) Polar basic force S, hydroxyl group, amide group, carboxyl group, amino group, carbonate group, carbamate group, sulfonamide group, sulfonic acid group, phosphonic acid group of the polar silicone component

The ophthalmic lens as described in (4) above, which is a group selected from the group consisting of methoxyethyl group, methoxyethoxyethyl group, hydroxyethyl group, and hydroxyethoxyethyl group.

(6) At least one of the silicone components is represented by the following general formula (a)

M-L- Sx (a)

The ophthalmic lens according to any one of (3) to (5) above, which has a structure obtained from a silicone monomer represented by

(M represents a polymerizable group capable of radical polymerization. L represents an optionally substituted divalent organic group having 1 to 20 carbon atoms. A represents a siloxanyl group.)

(7) L in the above formula (a) is the following general formula (b), (c)

[0005] [Chemical 1]

—— (CH ₂ ) j—— (b)

OH (CH ₂ CHCH ₂ ) _k — O—— (CH ₂ ) _m — (c)

[0006] The ophthalmic lens as described in (6) above, wherein!

(j represents an integer from 1 to 20. k represents an integer from 1 to 6, m represents an integer from 1 to 17; however, 3k + m≤20.)

(8) The ophthalmic lens according to (7), wherein L in the formula (a) is a group represented by the general formula (c).

(9) At least one of the silicone monomers is represented by the following formulas (d), (e) and (g) [0007] [Chemical Formula 2]

[0008] The ophthalmic lens as described in (6) above, which is a monomer selected from the group consisting of force and the like.

(10) The ophthalmic lens according to the above (9), wherein at least one of the silicone monomers is a silicone monomer selected from the group consisting of the formulas (e) and (g).

(11) The ophthalmic lens according to (1) to (10), wherein the content of the polymer compound (A) is 0.0;! To 20% by weight. .

(12) The monomer having an ammonium group is represented by the following general formula (f)

[0009] [Chemical 3]

[0010] The ophthalmic lens according to any one of (1) to (; 1 1) above, (R ¹ represents an optionally substituted alkyl group having 1 to 30 carbon atoms. R ^{2 to} R ⁷ are substituted with 1 to 20 carbon atoms! /, May! /, Alkyl groups or carbon atoms. Represents 6 to 20 substituted! /, May! / Aryl groups, R ² may form a ring, and X— represents any anion.

(13) The above-mentioned (1) to (; 12), characterized by being obtained by polymerizing the monomer of the mouth-opening gel (B) or the macro-mouth monomer in a state of being mixed with the polymer compound (A). The ophthalmic lens according to any one of the above.

(14) The ophthalmic lens according to any one of (1) to (; 13) above, wherein the ophthalmic lens is a contact lens.

The invention's effect

[0011] According to the present invention, it is possible to obtain an ophthalmic lens that has excellent antibacterial properties and does not deteriorate even when washed with water.

BEST MODE FOR CARRYING OUT THE INVENTION

[0012] The ophthalmic lens of the present invention is obtained by dispersing a polymer compound having an ammonium group in a molecule in a hyde mouth gel which is a hydrophilic polymer having a network structure. In the present invention, that the polymer compound is dispersed in the hyde mouth gel does not include the case where the polymer compound is simply attached to the hyde mouth gel surface, and the ophthalmic lens surface is cleaned by ultrasonic cleaning using water. After washing, when the polymer compound contained in the ophthalmic lens is extracted with an organic solvent, the polymer compound having an ammonium group in the molecule is extracted. When a polymer compound having an ammonium group in the molecule is extracted by the extraction operation, it is determined that the polymer compound is dispersed in the gel. Specifically, extraction is performed using methanol, ethanol, 2-propanol, toluene, hexane, acetone, methyl ethyl ketone, ethyl acetate, butyl acetate, tetrahydrofuran, dimethyl sulfoxide as an organic solvent, and at least one of these is used. When a polymer compound having an ammonium group in the molecule is extracted by 0.1% or more of the dry weight of the hide-mouthed gel, it is determined that the polymer compound is dispersed.

[0013] The hydrophilic monomer used in the hide-mouthed gel (B) of the ophthalmic lens of the present invention is not particularly limited as long as it can be polymerized. (Meth) Atalyloyl group, styryl group, allyl group, bulle Monomers having other groups and other polymerizable carbon-carbon unsaturated bonds can be used.

[0014] In the following, force S that gives some examples, the present invention is not limited to these. (Meth) acrylic acid, itaconic acid, crotonic acid, carboxylic acids such as butyl benzoic acid, (meth) acrylates with hydroxyl groups such as 2-hydroxyxetyl (meth) acrylate, N, N-dimethyl acrylamide, etc. (Meth) acrylamides, N-Buylpyrrolidone, N-Vinylimidazole and the like. Of these, (meth) atrylamides such as N, N-dimethylacrylamide are preferred in view of the mechanical properties and long-term storage stability of the resulting silicone polymer. In order for the ophthalmic lens of the present invention to have sufficient oxygen permeability, the hydrogel is preferably a silicone hydride gel further containing a silicone component. If the content of the silicone component in the silicone hydride gel is small, the oxygen permeability necessary for continuous use of the ophthalmic lens cannot be obtained, and if it is large, the compatibility with the hydrophilic component is difficult to obtain. Therefore, when the total weight of various monomers is 100 parts by weight, the content of the silicone monomer is preferably 20 to 80 parts by weight, more preferably 30 to 80 parts by weight, and most preferably 50 to 80 parts by weight. ! /

[0015] When the hyde mouth gel (B) of the ophthalmic lens of the present invention is a silicone hyde mouth gel, a polymer compound having a hydrophobic silicone component and a monomer unit having a hydrophilic ammonium group ( In order to obtain sufficient compatibility with (A), it is preferable that 30% or more of the number of key atoms in the silicone component is a key atom in the polar silicone component, and more than 40% is more. 50% or more is most preferable.

[0016] Here, the polar silicone component represents a structure obtained by polymerizing a polar silicone monomer having a polar group in the molecule. Examples of polar groups include hydroxyl groups, amide groups, carboxynole groups, amino groups, carbonate groups, carbamate groups, sulfonamide groups, sulfonic acid groups, phosphonic acid groups, methoxyethyl groups, methoxyethoxyethyl groups, hydroxyethyl groups. Group, hydroxyethoxyethyl group and the like.

[0017] Further, when the ophthalmic lens of the present invention is a silicone nodule gel, in order to improve transparency, a hydroxyl group such as 2-hydroxyethyl (meth) acrylate is particularly used as a hydrophilic monomer. It is preferred to copolymerize (meth) acrylate monomers that have! use If the amount used is too small, the effect of improving transparency cannot be obtained. If too much is used, the physical properties of the polymer will be affected, so 0.;! ~ 25 parts by weight is preferred 0.5 to 20 parts by weight Parts are more preferred, 1.0-- 15 parts by weight is most preferred. If the number of hydroxyl groups in the ophthalmic lens is OH and the number of ammonium nitrogen is N, if the N / OH ratio is too small, sufficient antibacterial properties cannot be obtained, and if it is too large, the ophthalmic lens has sufficient transparency. In this case, 0.001 to 0.5 is preferable, 0.005 to 0.4 is more preferable, 0.0;! To 0.3 is also preferable. In addition, the method for measuring the N / OH ratio is selected according to the type and amount of each component in the hide-mouth gel and the antibacterial polymer, and examples thereof include nuclear magnetic resonance (NMR) and infrared spectroscopy. (IR), elemental analysis, total reflection infrared absorption measurement (ATR), ultraviolet spectroscopy (UV), various general measurement methods such as titration method, and combinations thereof. Examples of the polymerization method of the silicone hydride gel used in the ophthalmic lens of the present invention include a method obtained by polymerizing a mixture of various monomers such as a silicone monomer, a hydrophilic monomer, and a crosslinking monomer, a silicone monomer, a hydrophilic monomer, and the like. Examples include a method in which various monomers are homopolymerized or copolymerized, and then a macromonomer having a polymerizable group introduced is polymerized.

[0018] The silicone monomer obtained by polymerizing the silicone hydride gel of the present invention from a monomer functions as a cross-linking agent when it has two or more polymerizable groups, and the resulting elastic modulus of the silicone nodulogel Is too high, the following general formula (a)

M-L- Sx (a)

A silicone monomer having a structure having one polymerizable group in the molecule is preferred! /.

In the formula (a), Μ represents a polymerizable group capable of radical polymerization. Examples of the polymerizable group capable of radical polymerization include vinylene group, vinylol group, vinyloxy group, aryloxy group, bull force rubamate group, aryl carbamate group, bull carbonate group, aryl carbonate group, metatalolyl group, allyloyl group, styryl group. Groups and the like. Of these, the attalyloyl group and the methacryloyl group are preferable from the viewpoint of the elastic modulus of the obtained polymer.

[0020] In the formula (a), L represents an optionally substituted divalent organic group having carbon number; In order to lower the elastic modulus of the obtained polymer, an alkylene group is more preferable. In order to obtain compatibility with a hydrophilic monomer, it is more preferable to have a hydroxyl group or an ethylene oxide structure. Examples include a methylene group, an ethylene group, a propylene group, a 1 methylethylene group, a 2-methyl group. Divalent hydrocarbon groups such as tilethylene, n-propylene, n-butylene, 2-methylpropylene, 2,2-dimethylpropylene, n-pentylene, 2-hydroxypropylene, 2-hydroxybutylene, 3 A divalent organic group having a hydroxyl group such as a hydroxybutylene group, a divalent organic group having an ether bond as represented by the following formulas (L1 ;!) to (L3), and the following formula ( Examples thereof include divalent organic groups having both an ether bond and a hydroxyl group represented by formulas such as L 4) and (L 5).

[0021] [Chemical 4]

[0022] Of these, the formula (b) or (c)

[0023] [Chemical 5] (CH ₂ ); (b)

OH

(CH ₂ CHCH ₂ ) _k — O—— (CH ₂ ) _m — (c)

[0024] The group represented by the formula (c) is more preferred. Furthermore, k = l in equation (c)

M is most preferably 1-5.

In the formula (a), Sx represents a siloxanyl group. Here, the siloxanyl group represents a group having at least one Si—O—Si bond in the structure.

[0026] The silicone monomer represented by the general formula (a) is preferably the one represented by the following general formula (a ').

[0027] [Chemical 6]

[0028] n represents an integer of 0 to 200. a, b and c each independently represents an integer of 0 to 20. n + a + b + c represents the number of siloxane bonds in the silicone compound. If the number of n + a + b + c is too small, the oxygen permeability required for ophthalmic lenses and contact lenses will be sufficient. If the amount is too large, the compatibility with various hydrophilic monomers often used as a copolymerization component is reduced, and a transparent lens cannot be obtained. More preferably, 2 to 50 is most preferable.

[0029] Ai A ¹¹ represents an optionally substituted alkyl group having 1 to 20 carbon atoms or an optionally substituted aryl group having 6 to 20 carbon atoms. Substituent represented by the above structure Among them, the compound having such a substituent is industrially available at a relatively low cost.

) A group selected from the group consisting of a silyl group, a dimethyltrimethyloxysilyl group, and a poly (dimethylsiloxane) group.

[0030] Among the silicone monomers represented by the general formula (a), those that are preferable in terms of compatibility with hydrophilic monomers and ammonium salt monomers, oxygen permeability of polymers obtained by polymerization, mechanical properties, and the like are preferable. The following formula (d), (e), (g)

[0031] [Chemical 7]

(In the formula (g), Q represents an alkyl group having 1 to 8 carbon atoms. P represents an integer of 1 to 20). Furthermore, since a transparent silicone polymer can be easily obtained even when mixed with an internal wetting agent such as polybulurpyrrolidone, a silicone monomer having a hydroxyl group in the molecule as represented by formula (e) or formula (i). Is most preferred.

[0033] In the present invention, the macromonomer is a monomer having a molecular weight of 800 or more and having one or more polymerizable groups.

[0034] When the silicone nodule gel used in the ophthalmic lens of the present invention is obtained from a macromonomer, the above-mentioned various silicone monomers are homopolymerized and then introduced with a polymerizable group to co-polymerize with various hydrophilic monomers and the like. Polymerization method, various silicone monomers, various hydrophilic monomers And the like, and then polymerizing by introducing a polymerizable group. Among these, a method in which various silicone monomers and various hydrophilic monomers are copolymerized and then a polymerizable group is introduced and polymerized is preferable because compatibility between the silicone component and the hydrophilic component is easily increased.

[0035] If the molecular weight of the silicone macromonomer is too low, one of the advantages of using the macromonomer is that the effect of inhibiting polymerization shrinkage is not sufficient, and if the molecular weight is too high, the viscosity of the macromonomer becomes too high and handling becomes difficult. From the viewpoint of lowering the solubility in the polymerization solvent, 1000 to 1,000,000 S is preferable, 3000 to 500,000 S is more preferable, and 500 00 to 100,000 is most preferable.

[0036] The ammonium salt monomer constituting the polymer compound used in the ophthalmic lens of the present invention may be any monomer having a polymerizable group and an ammonium cation in the molecule. The polymerizable group is not particularly limited as long as it can be radically polymerized. (Meth) Ataryloyl group, (meth) acrylamido group, styryl group, allyl group, bur group, and other radically polymerizable carbon-carbon unsaturated bonds A group having In addition, the ammonium cation may be independently substituted with three substituent groups other than one leading to a polymerizable group on the nitrogen atom, or may be substituted with an alkyl group having 1 to 20 carbon atoms or substituted! / Or, it is an aryl group having 6 to 20 carbon atoms, and these substituents may form a ring with each other. Examples of more specific structures are the following general formulas (f), (h), (i)

[0037] [Chemical 8]

[0039] (In the formulas (h) and (i), R ^{8 to} R ^{1 ()} are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms or an optionally substituted carbon number 6 Represents an aryl group of ˜20, R ¹¹ represents hydrogen or a methyl group, Z represents O or NH, X— represents an arbitrary anion, and the like. Among them, the burium imidazolium salt represented by the general formula (f) is most preferable in terms of heat stability and antibacterial properties.

In general formula (f), R ¹ represents an optionally substituted alkyl group having 1 to 30 carbon atoms. If the number of carbon atoms is small, the hydrophilicity of the ammonium cation moiety makes it compatible with the silicone monomer. When the number of carbon atoms is too low, the compatibility with hydrophilic monomers decreases, so 4 to 20 carbon atoms are more preferred! /.

In general formula (f), R ^{2 to} R ⁷ are optionally substituted alkyl groups having 1 to 20 carbon atoms or substituted with 6 to 20 carbon atoms! /, May! /, Aryl Represents a group. R ² may form a ring! / ヽ.

In the general formula (f), X— represents an arbitrary anion. Examples thereof include halide ions such as fluoride ions, chloride ions, bromide ions, iodide ions, hydroxide ions, sulfate ions, nitrate ions, boron tetrafluoride ions, and the like. Of these, halide ions are most preferred from the viewpoint of ease of synthesis.

[0043] The polymer compound of the present invention may be a homopolymer of ammonium salt monomers or a copolymer with other monomers. When the total weight of the various monomers in the copolymer is 100 parts by weight, the content of the ammonium salt monomer is too small to obtain sufficient antibacterial properties. More than 30 parts by weight is most preferred!

[0044] Examples of the monomer in the case where the polymer compound used in the ophthalmic lens of the present invention is copolymerized with a monomer other than the ammonium salt monomer are not particularly limited as long as copolymerization is possible (meta-metabolism). ) Monomers having an allyloyl group, a styryl group, a allyl group, a bur group, and other polymerizable carbon'carbon unsaturated bonds can be used. Examples include amide monomers such as N-Buylpyrrolidone, N, N-Dimethylacrylamide, N-Buylformamide, N-Bulucacetamide, 2-Hydroxyethyl methacrylate, and 2 (2-Hydroxyl). Monomers having a hydroxyl group such as ethoxy) ethyl methacrylate, silicone monomers such as 3-tris (trimethylsiloxy) silylpropyl methacrylate, polydimethylsiloxane having a (meth) acryl group at one or both ends And so on. Among these, an amide monomer and a monomer having a hydroxyl group are more preferable because they are easily compatible with an ammonium salt monomer, and N-vinylpyrrolidone is most preferable.

[0045] If the molecular weight of the polymer compound used in the ophthalmic lens of the present invention is too small, the polymer compound is likely to elute the substrate, and if it is too large, the polymer compound monomer mixture or a liquid containing it is contained. Since the solubility with respect to the immersion solution is lowered, 1000 to 1 million, preferably S, more preferably 5,000 to 500,000, most preferably 10,000 to 300,000.

[0046] If the content of the polymer compound used in the ophthalmic lens of the present invention is too small, sufficient antibacterial properties cannot be obtained, and if it is too large, sufficient transparency cannot be obtained. ! ~ 20% by weight is preferred 0.5 ~; 15% by weight is more preferred;! ~ 10% by weight is most preferred.

[0047] In the ophthalmic lens of the present invention, two or more copolymerizable carbons in one molecule are obtained in the sense that good mechanical properties are obtained and good resistance to a disinfecting solution and a cleaning solution is obtained. It is preferable to use a monomer having a carbon unsaturated bond as a copolymerization component. The copolymerization ratio of two or more copolymerizable carbon-carbon unsaturated bonds in one molecule is preferably 0.;! To 20% by weight, preferably 0.3 to 15% by weight, more preferably 0 5 to 10% by weight is more preferable.

[0048] The ophthalmic lens of the present invention may contain an ultraviolet absorber, a pigment, a colorant, and the like! It may also contain UV-absorbers, dyes, and colorants having a polymerizable group in a copolymerized form! / ヽ

Yes

[0049] When the ophthalmic lens of the present invention is obtained by polymerization, it is preferable to add a thermal polymerization initiator typified by a peroxide or a azo compound or a photopolymerization initiator in order to facilitate polymerization. . When performing thermal polymerization, select one having the optimum decomposition characteristics for the desired reaction temperature. In general, azo initiators and peroxide initiators having a 10-hour half-life temperature of 40 ° C to 120 ° C are suitable. Examples of the photopolymerization initiator include carbonyl compounds, peroxides, azo compounds, sulfur compounds, halogen compounds, and metal salts. These polymerization initiators are used alone or in combination, and are used in an amount of up to about 1% by weight.

[0050] When the ophthalmic lens of the present invention is obtained by polymerization, a polymerization solvent can be used. As the solvent, various organic and inorganic solvents are applicable and there is no particular limitation. For example, water, methanol, ethanol, propanol, 2-propanol, butanol, tert-butanol, tert-amyl alcohol, 3,7-dimethyl-3-octanol and other alcohol solvents, benzene, toluene, xylene Various aromatic hydrocarbon solvents such as hexane, heptane, octane, decane, petroleum ether, kerosene, rig in, para Various aliphatic hydrocarbon solvents such as fins, various ketone solvents such as acetone, methyl ethyl ketone and methyl isobutyl ketone, various ester systems such as ethyl acetate, butyl acetate, methyl benzoate, dioctyl phthalate and ethylene glycol diacetate Solvent, Jetino ether, Tetrahydrofuran, Dioxane, Ethylene glycol dialkyl ether, Diethylene glycolino resin quinoleate, Triethylene glycol resin resin, Tetraethylene glycol dialkyl ether, Polyethylene glycol dialkyl ether, Polyethylene Glycol Polypropylene glycol block copolymer, Polyethylene glycol Polypropylene glycol Random copolymer and other glycol ether solvents They can be used alone or in combination.

[0051] As the polymerization method and molding method for the ophthalmic lens of the present invention, ordinary methods can be used. For example, a method of once forming a round bar or a plate and processing it into a desired shape by cutting or the like, a mold polymerization method, a spin cast method, or the like.

As an example, the case where the ophthalmic lens of the present invention is obtained by the mold polymerization method will be described below.

[0052] The monomer composition is filled in the space between two molds having a certain shape. Then, photopolymerization or thermal polymerization is performed to shape the mold. The mold is made of resin, glass, ceramics, metal, etc., but in the case of photopolymerization, an optically transparent material is used, and usually resin or glass is used. When a polymer is produced, in many cases, a void is formed by two opposing molds, and the force S that fills the void with the monomer composition S, and depending on the shape of the mold and the properties of the monomer, A gasket having the purpose of giving a constant thickness and preventing leakage of the filled monomer composition may be used in combination. Subsequently, the mold in which the voids are filled with the monomer composition is heated by being put in an oven or a liquid bath with the power to be irradiated with an actinic ray such as ultraviolet rays to polymerize the monomer. There may be a method in which both are used in combination, such as heat polymerization after photopolymerization or conversely photopolymerization after heat polymerization. In the case of photopolymerization, it is common to irradiate light containing a large amount of ultraviolet light using a mercury lamp or insect trap as a light source for a short time (usually 1 hour or less). In the case of thermal polymerization, the condition of gradually increasing the temperature near room temperature and raising the temperature to 60 ° C to 200 ° C over several hours to several tens of hours is the optical uniformity of the polymer, Grade Is preferred in order to maintain and improve reproducibility.

[0053] In the ophthalmic lens of the present invention, in order to maintain the antibacterial effect, the high molecular compound is dispersed in the network structure of the base hydrated gel. As an example of a method of dispersing a polymer compound in a base material, a method of polymerizing a hide-mouth gel in a state where a polymer compound is mixed in a raw monomer or raw material macromonomer mixture of a hide-mouth gel, Examples include a method of impregnating by impregnating in a solution of a molecular compound.

[0054] In the case of a method in which a high molecular weight compound is mixed in a state where a high molecular compound is mixed in a liquid mixture of anodic gel monomer, sufficient antibacterial properties cannot be obtained if the content of the high molecular compound is too small. When the amount is too large, the solid content of the gel is reduced. 0 to 20% is preferable 0.5 to 15% is more preferable; 10 to 10% is most preferable.

[0055] In the case of the method of immersing and impregnating a hydrated gel in a polymer compound solution, various organic and inorganic solvents can be applied to the polymer compound solution, and there is no particular limitation. . Examples include water, methanol, ethanol, propanol, 2-propanol monoole, butanol, tert-butanol, tert-amyl alcohol, various alcohol solvents such as 3,7-dimethyl-3-octanol, benzene, toluene, xylene, etc. Various aromatic hydrocarbon solvents, hexane, heptane, octane, decane, petroleum ether, kerosene, rigging, paraffin and other aliphatic hydrocarbon solvents, acetone, methyl ethyl ketone, methyl isobutyl ketone and other ketones Solvents, ethyl acetate, butylacetate, methyl benzoate, dioctyl phthalate, ethylene glycol diacetate, and other ester solvents, jetyl ether, tetrahydrofuran, dioxane, ethylene glycol monoresidanolenoquine ethere, diethylene Glico Resinolequinoleateol, triethylene glycol dialkyl ether, tetraethylene glycol dialkyl ether, polyethylene glycol monoresinoleateolene, polyethylene glycol mononore polypropylene glycol mononore block copolymer, polyethylene glycol polypropylene glycol random co These are various Daricol ether solvents such as polymers, and these can be used alone or in combination. Of these, water is most preferred.

[0056] If the concentration of the aqueous solution of the polymer compound is too low, sufficient antibacterial properties cannot be obtained, and if it is too high, it may be necessary to wash the excess polymer compound. 30% preferred 0.5 to 20% is more preferred;! To 10% is most preferred.

[0057] The ophthalmic lens of the present invention can be modified by various methods. It is preferable to perform a modification treatment that improves the wettability of the surface.

[0058] Specific reforming methods include electromagnetic wave (including light) irradiation, plasma irradiation, chemical vapor deposition treatment such as vapor deposition and sputtering, heating, base treatment, acid treatment, and other suitable surfaces. Mention may be made of the use of treatment agents and combinations thereof. Among these reforming means, simple and preferred are base and acid treatments.

[0059] Examples of the base treatment or acid treatment include a method of contacting an ophthalmic lens with a basic or acidic solution, a method of contacting an ophthalmic lens with a basic or acidic gas, and the like. More specific methods include, for example, a method in which an ophthalmic lens is immersed in a basic or acidic solution, a method in which a basic or acidic solution or basic or acidic gas is sprayed on an ophthalmic lens, or an ophthalmic lens. For example, a method of applying a basic or acidic solution with a spatula, a brush or the like, and applying a basic or acidic solution to an ophthalmic lens by a spin coating method or a dip coating method can be cited. The most simple method for obtaining a great modification effect is a method of immersing an ophthalmic lens in a basic or acidic solution.

[0060] The temperature at which the ophthalmic lens is immersed in a basic or acidic solution is not particularly limited, but is usually within a temperature range of about 50 ° C to 300 ° C. Considering workability, a temperature range of 10 ° C to 150 ° C is more preferable-5 ° C to 60 ° C is most preferable.

The time when the ophthalmic lens is immersed in a basic or acidic solution! /, The force that changes the optimum time depending on the temperature Generally 0.;! ~ 100 hours are preferred 0.3 ~ 24 hours Is more preferable within 0.5; most preferably within 12 hours. If the contact time is too short, a sufficient treatment effect cannot be obtained, and if the contact time is too long, if workability and productivity are deteriorated, not only the power but also the oxygen permeability and mechanical properties are reduced. There may be adverse effects.

[0061] Examples of the base include alkali metal hydroxides, alkaline earth metal hydroxides, various carbonates, various borates, various phosphates, ammonia, various ammonium salts, various amines and polyethyleneimine, High molecular weight bases such as polybulamine can be used. Of these, alkali metal hydroxides are most preferred because of their low cost and great treatment effect. [0062] Examples of acids include various inorganic acids such as sulfuric acid, phosphoric acid, hydrochloric acid, and nitric acid, various organic acids such as acetic acid, formic acid, benzoic acid, and phenol, and various high molecular weight acids such as polyacrylic acid and polystyrene sulfonic acid. It can be used. Among these, polyacrylic acid is most preferable from the viewpoint of acidity and solubility among those preferred to high molecular weight acids because they have a large treatment effect and little adverse effect on other physical properties. .

[0063] As the solvent of the basic or acidic solution, various inorganic and organic solvents can be used. For example, water, methanol, ethanol, propanol, 2-propanol, butanol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, glycerol and other alcohols, benzene, toluene, xylene Various aromatic hydrocarbons such as hexane, heptane, octane, decane, petroleum ether, kerosene, lignin, paraffin and other aliphatic hydrocarbons, acetone, methyl ethyl ketone, methyl isobutyl ketone and other ketones, acetic acid Various esters such as ethyl acetate, butylacetate, methyl benzoate, dioctyl phthalate, etc., jetyl ether, tetrahydrofuran, dioxane, ethylene glycol dialkyl ether, ethylene glycol Various ethers such as ethylene glycolino resinate, triethylene glycolino resinate, and ethylene ethylene glycolino resin. Various aprotic polar solvents such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, dimethylimidazolidinone, hexamethylphosphoric triamide, dimethyl sulfoxide, methylene chloride, chloroform, dichloroethane, Halogen solvents such as trichloroethane and trichlorethylene, and fluorocarbon solvents. Of these, water is most preferable from the viewpoints of economy, ease of handling, chemical stability, and the like. As the solvent, a mixture of two or more substances can be used.

[0064] The basic or acidic solution used in the present invention may contain a basic or acidic substance and components other than the solvent.

[0065] The ophthalmic lens is treated with a force S to remove a basic or acidic substance by washing after the base treatment or the acid treatment.

[0066] As the cleaning solvent, various inorganic and organic solvents can be used. For example, water, methanol, ethanol, prono, 2-prono, butanol, ethylene glycol, Tylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, various alcohols such as glycerin, various aromatic hydrocarbons such as benzene, toluene, xylene, hexane, heptane, octane, decane, petroleum ether, Various aliphatic hydrocarbons such as kerosene, ligroin and norafine, various ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, various esters such as ethyl acetate, butyl acetate, methyl benzoate and dioctyl phthalate , Jetyl ether, tetrahydrofuran, dioxane, ethylene glycol dialkyl ether, diethylene glycol dialkyl ether, triethylene glycol dialkyl ether, tetraethylene glycol dialkyl ether , Various ethers such as polyethylene glycol dialkyl ether, various aprotic polar solvents such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, dimethylimidazolidinone, hexamethylphosphoric triamide, dimethyl sulfoxide, chloride Halogen solvents such as methylene, chloroform, dichloroethane, trichloroethane, trichloroethylene, and chlorofluorocarbon solvents.

[0067] As the cleaning solvent, a mixture of two or more kinds of solvents may be used. The cleaning solvent may contain components other than the solvent, such as inorganic salts, surfactants, and cleaning agents.

[0068] The modification treatment may be performed on the entire ophthalmic lens, or may be performed only on a part of the ophthalmic lens, for example, only on the surface. When only the surface is modified, only the water wettability of the surface can be improved without greatly changing the properties of the entire ophthalmic lens, and the surface water of the ophthalmic lens using the polymer of the present invention can be improved. As another method to improve wettability, internal wettability is achieved by polymerizing the monomer mixture at the time of polymerization with a hydrophilic polymer added, and retaining the hydrophilic polymer in the ophthalmic lens to improve the surface water wettability. Pharmacological power S Examples of hydrophilic polymers used as internal wetting agents include polybulu cyclic amides such as polybulurpyrrolidone, polybulu cyclic amines such as polybutimidazole, polyacrylamides such as poly N, N-dimethylacrylamide, and polybular alcohol. And polyalcohols such as polyacrylic acid, polycarboxylic acids such as polyacrylic acid, polyethylene glycols, mixtures thereof, and copolymers. Of these, the eyes Most preferred from the viewpoint of improving the wettability of the lens surface is polybulurpyrrolidone.

[0069] If the oxygen permeability of the ophthalmic lens of the present invention is too low, eye damage occurs due to lack of oxygen especially during continuous wear, and if it is too high, various physical properties required for other ophthalmic lenses are obtained. Oxygen permeability coefficient 70 X 10— ^{U to} 500 X 10— ^u (cm ² / sec) mLO / (mL -h

2

Pa) is preferred.

[0070] The antibacterial properties of the ophthalmic lens of the present invention are as follows. When the number of bacteria in 3 samples was measured with Pseudomonas aeruginosa, the average of the number of bacteria after cultivation was 3 times the initial number of bacteria before culture. If it is within 4 times the average number of times, it is considered that there is no growth and is judged to have antimicrobial effect. More preferably, it is 10% or less of the average number of control bacteria, and most preferably 1% or less of the number of control bacteria.

[0071] The polymer of the present invention is particularly suitable as an ophthalmic lens such as a contact lens, an intraocular lens, and an artificial cornea.

Example

[0072] Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited thereto.

[0073] Example 1

The following formula (yl)

[0074] [Chemical 10]

[0075] a silicone compound (28.8 parts by weight), N, N-dimethylacrylamide (35.5 parts by weight), the following formula (y2)

[0076] [Chemical 11]

[0077] A polydimethylsiloxane having a molecular weight of about 1000, 28.

8 parts by weight), 2-hydroxyethyl methacrylate (3 · 8 parts by weight), tri (ethylene glycol) dimetatalylate (3 · 30 parts by weight), and a monomer unit having an ammonium group in the molecule. Molecular compound (Molecular weight approx. 40000, PVP / Burmethylimidazolium chloride = 9 5/5, 6 parts by weight), Photoinitiator Irgacure 1850 (1.0 part by weight), 3, 7-dimethyl-3-octanol (46 parts by weight) ) Were mixed and stirred. The N / OH ratio of this composition is calculated to be 0.24. The monomer mixture was degassed under an argon atmosphere. Place the center of a 100-m-thick parafilm between two 10-cm square and 3-mm-thick glass plates in a nitrogen atmosphere (one of them is affixed with an aluminum seal to make it easier to peel off). Put the cut out as a two-sheet spacer, pour the monomer mixture into it, and polymerize between plates by light irradiation (Toshiba F L6D fluorescent lamp, 8.4 kilolux, 15 minutes) to obtain a film sample It was.

[0078] The obtained film-like sample was peeled from the glass plate by applying ultrasonic waves in water for 20 minutes, immersed in a 60% IPA aqueous solution at 60 ° C, and further immersed in an 80% IPA aqueous solution at 60 ° C. Impregnation such as residual monomer was extracted by immersion for 2 hours, and hydrated by immersing in 50% IPA aqueous solution, 25% aqueous solution, and water with gradually decreasing IPA concentration for approximately 30 minutes. It was immersed in a borate buffer solution (ρΗ7 ·;!-7.3) in a 200 mL glass bottle, and the glass bottle was placed in an autoclave and boiled at 121 ° C. for 30 minutes. After allowing to cool, the film-like sample was taken out from the glass bottle and immersed in a borate buffer (ρΗ7 · !!-7.3). The obtained film-like sample was cut into 3 cm squares to obtain antibacterial evaluation samples.

[0079] After the sample obtained in Example 1 was vacuum-dried at 40 ° C for 16 hours, 2 g was taken, ultrasonically washed in distilled water for 30 minutes, then immersed in 2-propanol at 60 ° Heated at C for 24 hours. Evaporate the solvent from the extract using an evaporator, and then reduce the pressure using a vacuum pump. Then, when the residual solvent was completely removed and the weight was measured, the extract was 56.9 mg. In addition, from the infrared absorption spectrum, this extract was found to be a PVP / Burmethyl imidazolium glycide copolymer. From this, it was confirmed that the polymer of Example 1 was not dispersed with a polymer compound having a monomer unit having an ammonium group in the molecule.

[0080] Synthesis Example 1

To a 50 mL eggplant flask, add N-Buylimidazole (4.71 g, 50 mmol), iodinated notachinole (12. 01 g, 50 mmol), 2,6-di-tert-butyl 4-methylphenol (BHT, 0.1672 g), 65 ° Heated at C for 14 hours. After the reaction, 90 g of silica gel was used, and chloroform / methanolate = 50/1 (360 mL) → 30 / l (360 mL) → 20 / l (360 mL) → 10 / l (180 mL) → 5 / l (180 mU as eluent) The fraction containing the target spot was collected by TLC, and the solvent was distilled off by an evaporator to obtain a yellow oily ammonium salt monomer represented by the following formula (xl).

[0081] [Chemical 12]

(xl) Synthesis example 2

The monomer (lg) represented by the formula (xl) obtained in Synthesis Example 1 above, 3,7 dimethyl-3-octanol (lg), and photoinitiator Irgacure 1850 (0.02 g) were mixed and stirred. This monomer mixture was degassed under an argon atmosphere and poured into a petri dish having a diameter of 5 cm in a glove box under a nitrogen atmosphere. Light irradiation (Toshiba FL6D fluorescent lamp, 8.4 kilolux, 15 minutes), dissolved in as little methanol as possible, dropped into 500 mL of ethyl acetate with stirring, and allowed to stand at 5 ° C for 3 hours. The solid content obtained by filtration was washed with a small amount of ethyl acetate, and the solvent was distilled off by reducing the pressure in a desiccator. Poly (Buluo), which is a homopolymer of the monomer represented by the above formula (xl). (Cutyl imidazolium iodide) was obtained.

[0083] Example 2

The monomer yarn is formed by a silicone compound represented by the formula (yl) (23 parts by weight), the following formula (y3) [0084] [Chemical Formula 13]

[0085] A silicone compound represented by (35 parts by weight), N, N-dimethylacrylamide (28 parts by weight), poly (bulurpyrrolidone) (K-90, 8 parts by weight), 2-hydroxyethyl methacrylate (12 parts by weight), tri (ethylene glycol) dimetatalylate (1 part by weight), polydimethylsiloxane catalyzed at both ends (Shin-Etsu Chemical X-22-164Α, 1 part by weight), in Synthesis Example 2 above In a mixture of the obtained poly (buluoctylimidazolium iodide) (3.7 parts by weight), photoinitiator Inore Gacure 1850 (1 part by weight), 3,7-dimethyl-3-octanol (14 parts by weight) The sample was subjected to the same polymerization and post-treatment as in Example 1 to obtain a sample for antibacterial evaluation.

[0086] Examples 3-4

A sample for antibacterial evaluation was obtained by performing polymerization and post-treatment according to the method of Example 2 except that the amount of poly (buluoctylimidazolium iodide) was changed as shown in Table 1 below.

[0087] [Table 1] Table 1

Usage weight Ν Ζ Η Ratio

Example 2 3 .8 0 .0 5

Example 3 5 .0 0 .0 7

Example 4 1 0. 0 0. 1 4 [0088] Comparative Example 1

A film sample was obtained in the same manner as in Example 1 except that the polymer compound was not added to the monomer mixture. It was cut into 3 cm square and used as an antibacterial evaluation sample.

[0089] After the sample obtained in Comparative Example 1 was vacuum-dried at 40 ° C for 16 hours, 2 g was taken, ultrasonically washed in distilled water for 30 minutes, and then immersed in 2 propanol at 60 ° C. For 24 hours. When the solvent was distilled off from the extract using an evaporator and the pressure was reduced with a vacuum pump to completely remove the remaining solvent and the weight was measured, the extract was 0.1 mg. In addition, extraction was carried out by changing the solvent to methanol, ethanol, toluene, hexane, acetone, methyl ethyl ketone, ethyl acetate, butyl acetate, tetrahydrofuran, or dimethyl sulfoxide, all of which were 0.1 weight of the dry weight of the sample. % Extract was not extracted.

[0090] Comparative Example 2

The film-like sample obtained in Comparative Example 1 was placed in a 50 mL screw tube and immersed in an aqueous solution of 1.7% PVP / polymethylvinylimidazolium chloride (95/5) at room temperature for 16 hours.

[0091] Antibacterial evaluation

Prepare three film-like samples obtained in Examples 1 to 4, JIS Z 2801: 2000 “Antimicrobial Processed Products Antibacterial Test Method 'Antimicrobial Effect” 5.2 Contact lenses based on test methods for plastic products Pseudomonas aeruginosa NBRC 13275, one of the typical bacteria seen at the time of use, is inoculated into a film sample, the number of bacteria immediately after inoculation (initial number of bacteria) and 35 ° C, 24 hours Antibacterial evaluation was performed by counting the number of later bacteria. The results are shown in Tables 2 and 3 below. The film-like sample obtained in Comparative Example 1 polymerized without adding a polymer compound showed growth compared to the initial number of bacteria. The film-like sample obtained in Example 1 showed a 1-digit decrease compared to the initial number of bacteria 1S. In addition, Examples 2-4 showed a 5-digit decrease, indicating sufficient antibacterial properties.

[0092] [Table 2] Table 2

Measurement 1 Measurement 2 Measurement 3 Average

Initial number of bacteria 2.60 X 10 ⁵ 2.80 X 10 ⁵ 2.40 X 105 2.60 X 105 Example 1 4.10 X 10 ⁴ 4.40 X 10+ 5.60 X 10 ³ 3.02 X 10 ⁴ Comparative example 1 7.80 X 10 ⁶ 6.10 X 106 6.71 X 10 ⁶ 6.87 X 106 [0093] [Table 3]

Table 3

[0094] Antibacterial evaluation after ultrasonic cleaning

The film samples obtained in Example 1 and Comparative Example 2 were immersed in 300 mL of distilled water, washed with ultrasonic waves for 15 minutes, then taken out and subjected to the same antibacterial evaluation as described above. The results are shown in Table 4 below, whereas the film-like sample obtained in Comparative Example 2 that was only immersed in an antibacterial polymer aqueous solution lost its antibacterial properties and showed bacterial growth. The film-like sample obtained in Example 1 was shown to have sufficient antibacterial properties even after ultrasonic cleaning.

[0095] The sample obtained in Comparative Example 2 was vacuum-dried at 40 ° C for 16 hours, then 2g was taken, ultrasonically washed in distilled water for 30 minutes, and then immersed in 2 propanol at 60 ° C. For 24 hours. When the solvent was distilled off from the extract using an evaporator and the pressure was reduced with a vacuum pump to completely remove the remaining solvent, and the weight was measured, the extract was 0.3 mg. In addition, extraction was carried out by changing the solvent to methanol, ethanol, toluene, hexane, acetone, methyl ethyl ketone, ethyl acetate, butyl acetate, tetrahydrofuran, or dimethyl sulfoxide, all of which were 0.1 weight of the dry weight of the sample. % Extract was not extracted.

[0096] [Table 4] Table 4

Example 5

Contact lens module made of transparent resin (poly-4-methylpentene 1) instead of glass plate A contact lens sample was obtained by boiling until the boiling was performed in the same manner as in Example 1 except that a lould was used.

Claims

The scope of the claims

[1] An ophthalmic lens comprising a polymer compound (A) having a monomer unit having an ammonium group in the molecule dispersed in a hydrated gel (B).

[2] When the number of alcoholic hydroxyl groups in the ophthalmic lens is represented by OH and the number of ammonium nitrogen by N

The ophthalmic lens according to claim 1, wherein the N / OH ratio is 0.001 -0.5.

[3] The ophthalmic lens according to [1] or [2], wherein the hide mouth gel (B) is a silicone gel or id mouth gel containing 20% by weight or more of a silicone component.

[4] The ophthalmic lens according to [3], wherein 50% or more of the number of key atoms in the silicone component in the hide mouth gel (B) is a key atom of the polar silicone component.

[5] Polar power of the polar silicone component, hydroxyl group, amide group, carboxyl group, amino group, carbonate group, carbamate group, sulfonamide group, sulfonic acid group, phosphonic acid group, methoxetyl group, methoxyethoxyethyl group 5. The ophthalmic lens according to claim 4, wherein the ophthalmic lens is a group selected from the group consisting of a hydroxyethyl group and a hydroxyethyl group.

[6] At least one of the silicone components is represented by the following general formula ω

M-L- Sx (a)

The ophthalmic lens according to claim 3, wherein the ophthalmic lens has a structure obtained from a silicone monomer represented by the formula:

[7] L in the above formula (a) is the following general formula (b), (c)

[Chemical 1 (CH ₂ ) j (b)

7. The ophthalmic lens according to claim 6, which is any one of OH (CH ₂ CHCH ₂ ) _k — 0— (CH ₂ ) _m — (c).

(j represents an integer of 1 to 20, k represents an integer of 1 to 6, m represents an integer of 1 to 17;

3k + m≤20. ) The ophthalmic lens according to claim 7, wherein L in the formula (a) is a group represented by the general formula (c).

Among the silicone monomers, at least one of the following formulas (d), (e) and (g)

[Chemical 2]

The ophthalmic lens according to claim 6, wherein the monomer is a selected group force.

(In the formula (g), R represents an alkyl group having 1 to 20 carbon atoms or an aryl group having 6 to 20 carbon atoms.

. n represents an integer of !!-20. )

10. The ophthalmic lens according to claim 9, wherein at least one of the silicone monomers is a silicone monomer selected from the group consisting of formulas (e) and (g).

[11] The content of the polymer compound (A) is 0.0 :! to 20% by weight.

! ~ 10! /, Ophthalmic lens according to any of the above.

[12] The monomer having an ammonium group is represented by the following general formula (f):

[Chemical 3]

The ophthalmic lens according to claim 1, wherein the ophthalmic lens is represented by: (R ¹ represents an optionally substituted alkyl group having 1 to 30 carbon atoms. R ^{2 to} R ⁷ may be substituted with 1 to 20 carbon atoms! /, An alkyl group or 6 carbon atoms. Substituent of ~ 20! Or may be! / Represents an aryl group, R ² may form a ring, X— represents an arbitrary anion)) [13] Polymer compound 13. The ophthalmic lens according to claim 1, wherein the ophthalmic lens is obtained by polymerizing the monomer or macromonomer of the hide-mouth gel (B) in a state of being mixed with (A).

[14] The ophthalmic lens according to any one of [1] to [13], wherein the ophthalmic lens is a contact lens.