JPH01299559A - Ophthalmic lens - Google Patents

Abstract

PURPOSE:To provide anophthalmic lens which bas ultraviolet ray absorption, safety, and durability, by a method wherein a specified acryl denatured benzophenon series polymeric ultraviolet ray absorbent having and a lens material constituting material are copolymerized. CONSTITUTION:One or at least two kinds of acryl denatured benzophenon series ultraviolet ray absorbents shown by a formula I are used properly. Approximate 0.5-15wt.% the absorbent is added in a monomer for constituting a given lens material, and the mixture is polymerized through a usual polymerizing process to produce a columnar polymer block. Usual mechanical processing is applied on the polymer block, or the mixture of the ultraviolet ray absorbent and the monomer for constituting a lens material is placed in a given molding container for polymerization. Y1, Y2 and Y3 in the formula I are selected from a group formed by hydrogen, a hydroxy group, and an alcoxy group and X group of C1-C18, and at least one of Y1, Y2 and Y3 is an X group. The X group is represented by a formula II, R1 in the formula II is selected from an alkyl group of C1-C8, and R2 is selected from hydrogen and a methyl group.

Description

[Detailed description of the invention] [Industrial application field]

TECHNICAL FIELD The present invention relates to an ophthalmic lens.

[Background of the invention]

Of the ultraviolet rays contained in sunlight, most of the ultraviolet rays below 286 nm are absorbed by the ozone layer in the upper atmosphere.
Light of longer wavelengths falls on the earth's surface. Of these lights, in eyes with crystalline lenses, 28
Ultraviolet rays with a wavelength of 0 to 320 n- are absorbed by the cornea, and 32
Near ultraviolet rays from 0 to 400n@ are absorbed by the crystalline lens,
Visible light of ~780n+* and near-infrared light of 780-1400nm reach the retina. Note that infrared rays with wavelengths of 1400 nm or more are absorbed by the cornea. Therefore, certain disorders of the eye or certain diseases of the eye,
For example, when the crystalline lens is surgically removed due to cataracts, 320-4
Near ultraviolet rays of 00 nm can reach the retina, and as a result, there is a possibility that it may cause damage to the retina. For this reason, those who have undergone crystalline lens extraction surgery and wear aphakic contact lenses or intraocular lenses need to have these ophthalmic lenses configured to absorb near ultraviolet rays with a wavelength of 320 to 400 nm. In addition, these ophthalmological lenses come into direct contact with the human body's mucous membranes or are implanted into the human body, so they are not biocompatible.
In addition, there is no risk of the lens component monomers being eluted by body fluids such as eye secretions and tears, and the ultraviolet absorber itself is not eluted, and it is highly biocompatible. There is a need. Therefore, in order to meet these strict requirements, research has been carried out on ophthalmic lenses containing ultraviolet absorbers that absorb the above-mentioned ultraviolet rays, but the results of the research to date are limited. is scarce. Among these research results, relatively good ones include, for example, 2.2 as shown in Japanese Patent Publication No. 52-48824 or US Pat. No. 4,304,895.
'-Dihydroxy-4,4'-dimethoxybenzo2-hydroxy-4-(2-hydroxy-3-methacryloxy)propyloxybenzophenone has been proposed. However, the above 2,2'-dihydroxy-4,4'
-Compounds such as dimethoxybenzophenone cannot react with the polymerizable polymers that make up ophthalmic lenses. This UV absorber, such as 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, moves through the polymer that makes up the ophthalmic lens, forming a layer containing a high concentration of UV absorber on the polymer surface. Although it is desirable to prevent the deterioration of the polymer itself due to ultraviolet rays, there is a high risk that the ultraviolet absorber will volatilize or elute from the polymer surface layer containing this high concentration of ultraviolet absorber. , this leaves concerns about safety. On the other hand, since ultraviolet absorbers such as 2-hydroxy-4-(2-hydroxy-3-methacryloxy)propyloxybenzophenone have polymerizable properties, it is possible to use these ultraviolet absorbers and ophthalmic lens components. If ophthalmic lenses are made from this copolymer by copolymerizing it with a monomer of the following, there will be no fear of UV absorbers acting on it, and it is said to have the advantage of being highly safe. However, since this 2-hydroxy-4-(2-hydroxy-3-methacryloxy)propyloxybenzophenone is produced by a reaction between 2,4-dihydroxybenzophenone and glycidyl methacrylate-1, its purity is limited due to manufacturing constraints. It is industrially difficult to achieve a content of 70% or more, and it is extremely difficult to purify because it is obtained as a yellow-brown liquid with high viscosity at room temperature and contains a large amount of impurities. Among these impurities, there is a non-polymerizable ultraviolet absorber such as 2,4-dihydroxybenzophenone, so this 2-hydroxy-4-(2-hydroxy-3-methacryloxy)propyloxybenzophenone When using 2,4-dihydroxybenzophenone, there is a large risk that ultraviolet absorbers such as 2,4-dihydroxybenzophenone will elute.
Polymerizable 2-hydroxy-4-(2-hydroxy-3-
The meaning of using (methacryloxy)propyloxybenzophenone will be greatly diminished. Furthermore, the polymer obtained by copolymerizing this ultraviolet absorber with other monomers by a conventional method is colored yellow, and is therefore unsuitable for use as an intraocular lens. Therefore, in order to solve these drawbacks, we have developed
As shown in Japanese Patent No. 52873, 2-hydroxy-4-(2-
When using hydroxy-3-methacryloxy)propyloxybenzophenone as an ultraviolet absorber for ophthalmic lenses, such an ultraviolet absorber and the polymerizable 2-hydroxy-4-(2-hydroxy A monomer mix was obtained in which methyl methacrylate, which is a monomer that reacts with -3-methacryloxy)propyloxybenzophenone to form a polymer for lenses, was dissolved in dry ethyl acetate, and a polymerization initiator was dissolved in dry ethyl acetate-1. Obtain a dissolved initiator mix and mix these monomer mixes with the initiator mix and heat to reflux to form methyl methacrylate and 2-hydroxy-4-(2-hydroxy-3-methacryloxy).
After copolymerizing with propyloxybenzophenone, the reaction mixture was cooled and then placed in 5 to 6 times the volume of anhydrous methanol.
Precipitating a copolymer with hydroxy-4-(2-hydroxy-3-methacryloxy)propyloxybenzophenone, grinding the precipitated solid copolymer into a fine powder, and drying it; The resulting product was subjected to Soxhlet extraction to extract unreacted substances and impurities, and a purified copolymer of methyl methacrylate and 2-hydroxy-4-(2-hydroxy-3-methacryloxy)propyloxybenzophenone was obtained. get. The purified product of this copolymer is then vacuum-dried, the finely powdered copolymer is dissolved in methyl methacrylate monomer, and the prepolymer solution thus obtained is polymerized and solidified to form an intraocular lens. A method for producing an intraocular lens has been proposed in which a material is obtained and the intraocular lens material is subjected to a predetermined mechanical processing to obtain an intraocular lens. That is, 2-hydroxy-4-(2-hydroxy-3
When constructing an intraocular lens using a polymerizable ultraviolet absorber such as (methacryloxy)propyloxybenzophenone, impurities often elute unless the complex and special manufacturing process described above is performed. It is claimed that a highly safe intraocular lens cannot be obtained. However, the method for manufacturing an intraocular lens as described above not only requires special techniques, but is also complicated and troublesome, resulting in a correspondingly high cost. Also, Special Publication No. 1983-501781 and Special Publication No. 1982-
501936, 2-hydroxy-4-(2-
methacryloyloxyethoxy)benzophenone and 2
-Hydroxy-4-(2-acryloyloxyethoxy)benzophenone has been proposed. However, the ultraviolet absorber described in this publication is
It has been found that benzophenone and acrylic groups are bonded through a straight-chain alkyl group such as ethyl group, which has the disadvantage of being easily hydrolyzed. In other words, ophthalmic lenses such as contact lenses or intraocular lenses are constantly in contact with body fluids such as tears.
Additionally, water-containing contact lenses are required to be repeatedly sterilized by boiling, which has been found to have the disadvantage of causing decomposition of ester groups due to hydrolysis and elution of benzophenone groups that contribute to ultraviolet absorption. It was. Therefore, such ultraviolet absorbers that are easily hydrolyzed, even if they are polymerizable, cannot be used as constituent materials for ophthalmic lenses such as contact lenses and intraocular lenses due to their safety and durability. I'm worried about that.

DISCLOSURE OF THE INVENTION 1 As the inventor of the present invention earnestly pursued research on the above-mentioned problems, he found that the general formula [AI 〈However, Y, ! 2. Y is hydrogen, human oxy group, Cl
-CI selected from the group consisting of an alkoxy group of I and an X group, Y7. At least one of Y2 and Y3 is an X group. The X group is selected and R2 is selected from the group consisting of hydrogen and methyl groups. The acrylic-modified benzophenone ultraviolet absorber represented by , which can then be produced by converting it into methacrylic ester or acrylic ester, making it possible to obtain a highly pure product.If necessary, it can also be easily further purified by recrystallization, resulting in an extremely pure product. Based on the fact that a high quality product was obtained, if the compound represented by the above general formula rA1 is used, there is no need to adopt a special production method as proposed in the above-mentioned Japanese Patent Application Laid-Open No. 61-52873. It has been found that a safe ophthalmic lens can be obtained. In addition, specifically enumerating the compounds represented by the above general formula [A], for example, 2-hydroxy-4-(2-methacryloxy)butoxybenzophenone 2,2'-dihydroxy-4-(2-methacryloxy)
Butoxybenzophenone 2.2'-dihydroxy-4-methoxy-4'-(Z-
methacryloxy)butoxybenzophenone 2.2'-dihydroxy-4,4'-bis1(2-methacryloxy)butoxybenzophenone 2-hydroxy-2',4.4'-1-lis[(2-
(methacryloxy)butoxy]pen, siphenon, etc. Then, one or more of these ultraviolet absorbers are used as appropriate, and such ultraviolet absorbers are added in an amount of about 0.1 to 15% by weight into a predetermined lens material constituent monomer. The cylindrical polymer block obtained through the polymerization process is subjected to ordinary mechanical processing, or the mixture of the ultraviolet absorber and the monomer for forming the lens material is placed in a predetermined molding container and polymerized. This provides ophthalmic lenses such as contact lenses or intraocular lenses. The monomer for forming the lens material is not limited to methyl methacrylate, but may also include materials for breathable contact lenses containing acrylic modified polyorganosiloxane, linear or branched fluorocarbons such as acrylic acid, methacrylic acid, and itaconic acid. Breathable contact lens material containing alkyl ester, water-containing contact lens material containing 2-hydroxyethyl methacrylate-1 and/or N-vinyl lactam as the main component, methyl methacrylate-1 as the main component hard contact lens or intraocular lens materials;
and JP-A-61-285425, JP-A-6128.
Suitable materials such as a contact lens material containing a perfluoroalkyl ether monomer whose terminal end is capped with a polymerizable group as disclosed in Japanese Patent No. 5428 may be mentioned. [Example 11 Table 1 A monomer mixture having the composition shown in Table 1 was injected into a cylindrical polypropylene polymerization tube with a diameter of 16+ m and a height of 10 rings, and after replacing the upper space with nitrogen, it was sealed and kept at 40°C for 20 hours in a displaced oven;
Thereafter, the polymer was kept at 70°C, 90°C, and 100°C for 10 hours each in turn, and then taken out from the mold and kept at 105°C in vacuum F for 10 hours to complete the polymerization. The polymer thus obtained is a colorless, transparent, hard solid, which is processed to have a thickness of 5 mm - 1 diameter of 12 mm.
After cutting it into a button shape of 5 mm in size, it was machined into the shape of the optical part of a contact lens and an intraocular lens. In order to investigate the properties of the ophthalmic lens obtained in this way, a disk with a thickness of 0.5 mm and a diameter of 12.5 mm was prepared by mirror-polishing the surface from the polymer obtained as described in E. A sample was obtained, and its visible light and ultraviolet transmission spectra were measured to determine the wavelength range of ultraviolet cut. Note that this spectrum is not shown in FIG. Further, an elution test of the ultraviolet absorber was conducted as follows. 14 button-shaped polymer-wrapped samples having a thickness of 5+*m and a diameter of 12.5 MII so that the total sample surface area corresponds to 600112 were immersed in 20 mN polypropylene glycol (molecule Mk 1000),
After this was left at 50° C. for 72 hours, it was filtered and the filtrate was designated as eluate I. Using the monomer mixture of the monomer mixture in Table 1 except for the ultraviolet absorber, the same procedure as above was carried out to polymerize the polymer.The same elution procedure as above was carried out, and the resulting filtration The solution was designated as effluent (■). 2-Hydroxy-4-(Z-methacryloxy)butoxybenzophenone was mixed with polypropylene glycol (molecular weight 1
Standard solution of various concentrations (0,10ppb) dissolved in
, 50ppb, 500ppm, ippm, 10p
pm) and polypropylene glycol (molecular weight 10
Using 00) as a control, the absorbance at 2851- was measured and a calibration curve was obtained. The detection limit at this time was 30 ppb. Next, put eluate 1 into the sample side cell and elution M II into the control side cell and measure the absorbance at 285 nn.
The concentration of the ultraviolet absorber in the eluate was determined from the inspection line, and the percentage of the eluted ultraviolet absorber relative to the total amount of added ultraviolet absorber was determined. These results are shown in Table 2. [Comparative Example 1] As a comparative example to Example 1, the ultraviolet absorber in the monomer composition shown in Table 1 of Example 1 was replaced with 2-hydroxy-4
-(2-hydroxy-3-methacryloxy)propyloxybenzophenone (trade name Perma-sorbH^
: National Starch (manufactured by Chemical Corporation) and the same procedure as in Example 1 was performed to obtain a polymer, which was a transparent yellow and hard solid. This polymer was subjected to light transmission spectrum measurements and elution tests in the same manner as in Example 1, and the results are shown in Table 2.

[Comparative Example 2] As a comparative example to Example 1, the ultraviolet absorber and its eel in the monomer composition shown in Table 1 of Example 1 were
'-Dihydroxy-4,4'-dimethoxybenzophenone (Product name: Uvinul D-49: BASF
The polymer obtained by substituting 0.5 part by weight of 0.5 parts by weight and performing the same operation as in Example 1 was a colorless, transparent, hard solid. This polymer was subjected to light transmission spectrum measurements and elution tests in the same manner as in Example 1, and the results are shown in Table 2.

[Example 2] Table 3 Using a monomer mixture having the composition shown in Table 3, an ophthalmic lens was obtained using an oxygen permeable contact lens material obtained by performing the same procedure as in Example 1. In order to investigate the various characteristics of ophthalmic lenses, we conducted light transmission spectrum measurements and elution tests in the same manner as in Example 1.
The results are shown in Table 4.

[Comparative Example 3] As a comparative example to Example 2, the ultraviolet absorber in the monomer composition shown in Table 3 of Example 2 was
-(2-hydroxy-3-methacryloxy)propyloxybenzophenone (trade name Perva-sorbH^
: National Starch (manufactured by Chemical Corporation) and the same procedure as in Example 1 was performed to obtain a polymer, which was a pale yellow, transparent, hard solid. This polymer was subjected to light transmission spectrum measurements and elution tests in the same manner as in Example 2, and the results are shown in Table 4.

[Comparative Example 4] As a comparative example to Example 2, the ultraviolet absorber in the monomer composition shown in Table 3 of Example 2 was replaced with 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (trade name: tlvinul). D-49 (manufactured by BASF) and the same procedure as in Example 1 was performed to obtain a polymer, which was a colorless, transparent, hard solid. This polymer was subjected to light transmission spectrum AT measurement and elution tests in the same manner as in Example 2, and the results are shown in Table 4.

[Examples 3 to 8] 95 parts by weight of methyl methacrylate, 5 parts by weight of ethylene glycol dimethacrylate, 2.2'-azobis=(2
, 4-dimethylvaleronitrile) to 0.2 parts by weight of the monomer mixture, 2-hydroxy-
Adding 0.5 parts to 7 parts by weight of 4-(2-methacryloxy)butoxybenzophenone and performing the same operations as in Example 1 to obtain an ophthalmic lens, and to examine various characteristics of this ophthalmic lens. Measurement of light transmission spectrum and elution test were conducted in the same manner as in Example 1, and the results are shown in Table 5. Regarding the ophthalmic lens material obtained in Example 8, 5 g of the ophthalmic lens material was taken, and 1 g of water was prepared based on Yakuhatsu No. 489 (May 10, 1985) [Intraocular Lens Approval Criteria].
00ml, heated at 100°C for 30 minutes with a reflux condenser, allowed to cool to room temperature, used this liquid as a test liquid, and used water as a control with a layer length of 10vm and a wavelength of 220 to 400n.
The absorbance at - was measured. The results are shown in Figure 2.

[Comparative Example 5] As a comparative example of the water eluent test of Example 8, the ultraviolet absorber of Example 8 was treated with 2-hydroxy-4-(2-hydroxy-3-methacryloxy)propyloxybenzophenone (trade name: Perma- sorb M^: manufactured by National Starch and Chemical Corporation), and the same procedure as in Example 8 was performed to obtain an ophthalmic
The same elution operation with water as in Example 8 was performed on the lens material for use in the lens, and the absorbance at a wavelength of 220 to 400 nm was measured. The results are shown in Figure 2. As shown in Figure 2, 2-hydroxy-4-(2-
An ophthalmic lens material obtained by a conventional polymerization method using hydroxy-3-methacryloxy)propyloxybenzophenone (trade name Perma-sorb M^; manufactured by National Starch and Chemical Corporation) is It can be seen that a considerable amount of the ultraviolet absorber is eluted even by the elution operation using water. [Example 9.101 95 parts by weight of methyl methacrylate, 5 parts by weight of ethylene glycol dimethacrylate, 2,2'-azobis-(2
, 4-dimethylvaleronitrile) to a monomer mixture of 0.2 parts by weight, an ultraviolet absorber (2,2'-dihydroxy-4,4'-bis[(2-methacryloxy)butoxy-1benzophenone (Example 9), 2-hydroxy-2'
, 1 part by weight of 4,4'-tris[(2-methacryloxy)butoxy-1benzophenone (Example 10)) was added, and the same operation as in Example was performed to obtain a colorless and transparent ophthalmic lens. In order to examine the various properties of the ophthalmological lens, measurements of light transmittance and elution test were conducted in the same manner as in Example 1. The results showed that the wavelength range for UV protection in Example 9 was 372 nm or less, the wavelength range for UV protection in Example 10 was 376n+s or less, and in both Examples, the UV absorber elution occurred. The concentration of the eluate in the test was below the detection limit, indicating that the elution amount was 0.0002% or less.

[Example 11] 92 parts by weight of methyl methacrylate, 5 parts by weight of ethylene glycol dimethacrylate, 0.2 parts by weight of dimethyl-2゜2'-azobisisobutyrate, 2-hydroxy-4
-(2-methacryloxy)butoxybenzophenone The same operation as in Example 1 was carried out using a monomer mixture containing 3 parts by weight to obtain an ophthalmic lens. Weigh out exactly 1 g and put it in a glass container with a stopper containing distilled water 501. After sealing the container, heat it to 100°C. Measure the absorbance of the eluate at 285 nm every 10 hours and check for changes in absorbance. Ta. The results are shown in FIG. The eluate used for absorbance measurement was returned to the glass container so that the volume of the eluate was always maintained at 50 ml.

[Comparative Example 6] As a comparative example of Example 11, 2-hydroxy-4-(2
- 2 disclosed in Japanese Patent Publication No. Sho 62-501781 and No. Sho 62-501936 as an ultraviolet absorber in place of methacryloxy)butoxybenzophenone
The same procedure was carried out using -hydroxy-4-di-2-methacryloyloxyethoxy)benzophenone, and the change in absorbance was investigated, which is shown in FIG. This result, as understood from the significant increase in absorbance at 285 nm, indicates that 2-hydroxy-4-(2-methacryloyloxyethoxy)benzophenone is hydrolyzed by boiling and benzophenone is eluted. . On the other hand, when 2-hydroxy-4-(2-methacryloxy)butoxybenzophenone is used,
It can be seen that there is little elution of benzophenone, and it is highly safe and durable.

[Example 12] 45 parts by weight of methacryloxyethoxyprobyltris(trimethylsiloxy)silane, methyl methacrylate-1.1
9 parts by weight, 8 parts by weight of methacrylic vi, 5 parts by weight of triethylene glycol dimethacrylate, 20 parts by weight of 2.2.2-trifluoroethyl methacrylate, 3 parts by weight of 2-hydroxy-4-(2-methacryloxy)butoxybenzophenone, dimethyl Elution test similar to Example 11 on the material of oxygen permeable contact lenses obtained in the same manner as Example 1 using -2,2'-azobisisobutyrate 0.2-weighted area was conducted to examine changes in absorbance. The results are shown in Figure 4.

[Comparative Example 7] As a comparative example of Example 12, 2-hydroxy-4-(2
The same procedure was carried out using 2-hydroxy-4-(2-methacryloyloxyethoxy)benzophenone as the ultraviolet absorber instead of -methacryloxy)butoxybenzophenone, and the change in absorbance was examined, which is shown in FIG. This result indicates that 2-hydroxy-4-(2-methacryloyloxyethoxy)benzophenone is hydrolyzed by boiling and the benzophenone is eluted, as understood from the significant increase in absorbance at 285ns+. . On the other hand, when 2-hydroxy-4-(2-methacryloxy)butoxy-1-inzophenone is used,
It can be seen that there is little elution of benzophenone, and it is highly safe and durable.

Example 13 95 parts by weight of 2-hydroxyethyl methacrylate, 0.5 parts by weight of ethylene glycol dimethacrylate, 4.5 parts by weight of methyl methacrylate, 2.2-azobis-(2
Example 11 A similar test was conducted, and the results are shown in Figure 5.

[Comparative Example 8] As a comparative example of Example 13, 2-hydroxy-4-(2
-Methacryloxy)butoxybenzophenone was replaced with 2-hydroxy-4-(2-methacryloyloxyethyloxy)benzophenone as the ultraviolet absorber, and the change in absorbance was investigated. This is shown in Figure 5. Indicated. This result is consistent with 2-hydroxy-4-(2-
This shows that benzophenone (methacryloyloxyethoxy) is hydrolyzed by boiling, and benzophenone is eluted. On the other hand, when 2-hydroxy-4-(2-methacryloxy)butoxybenzophenone is used,
It can be seen that there is little elution of benzophenone, and it is highly safe and durable.

[Brief explanation of the drawing]

FIG. 1 shows the light transmission spectrum of the material of the ophthalmic lens according to the present invention, and FIGS. 2 to 5 show the absorbance characteristics. Agent U Gao (
Self loquat. 7 Wavelength (nm) Figure 1 Figure 2 Boiling time (hours) Boiling time (hours) Figure 5

Claims (1)

[Claims] General formula▲ Numerical formula, chemical formula, table, etc.▼ (However, Y_1, Y_2, Y_3 are selected from the group consisting of hydrogen, hydroxy group, alkoxy group of C_1 to C_1_8, and X group, Y_1, At least one of Y_2 and Y_3 is an X group. An ophthalmological lens comprising a copolymer of an acrylic-modified benzophenone-based polymerizable ultraviolet absorber represented by (selected from the group consisting of methyl groups) and a lens material constituent material.