JP2009045329A - Intraocular lens and its manufacturing method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an intraocular lens capable of effectively suppressing secondary cataract developed by moving to a posterior lens capsule and multiplying of a lens epithelial cell after a cloudy lens and cortex are removed and the intraocular lens is inserted, and to provide its simplified manufacturing method. <P>SOLUTION: The intraocular lens manufacturing method includes applying a surface modifying treatment to an intraocular lens material and then bringing it into contact with a polar medium, and the intraocular lens is manufactured by the method. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for manufacturing an intraocular lens and an intraocular lens.

  More specifically, the present invention relates to a method for producing an intraocular lens capable of suppressing a post-cataract that occurs after surgery in an intraocular lens to be inserted after removal of a lens having cataract, and an intraocular produced by the method. It relates to lenses.

  In recent years, with the increase in the elderly population, the number of senile cataract patients has increased. Cataract is a disease in which the lens is clouded, and it induces a decrease in visual acuity depending on the degree of cloudiness, the region and the site, and sometimes it can cause blindness. Treatment of cataracts involves removing the turbid lens and cortex and either correcting vision with eyeglasses or contact lenses or inserting an intraocular lens. A method for fixing an intraocular lens is generally widely practiced.

  However, in this method, the posterior capsule opacities that occur when the remaining lens epithelial cells move (migrate) to the posterior capsule portion of the lens and proliferate may spread to the intraocular lens optical portion, and secondary cataract may occur. . As a method for treating such a subsequent cataract after insertion of an intraocular lens, a method of removing a turbid part by irradiation with Nd: YAG laser light is used. However, this method has a problem that the apparatus is expensive and obstructs fundus examination, photocoagulation, and vitreous surgery (for example, see Non-Patent Document 1).

  On the other hand, as a method for suppressing the occurrence of secondary cataract, a method using a drug (for example, see Patent Document 1), a method for making the peripheral part of an intraocular lens a sharp shape (for example, see Non-Patent Document 1), etc. However, there are issues such as the need to construct a new combination of intraocular lens and drug, and the need to add precision processing to sharpen the periphery of the lens. . In addition, a method of coating a biocompatible material on the surface of an intraocular lens (for example, see Patent Document 2) has been proposed, but at present, sufficiently satisfactory results have not been obtained.

For this reason, the applicant of the present invention controls the interaction between the intraocular lens and the cells by applying a surface modification treatment to the intraocular lens as a method for more easily producing an intraocular lens capable of suppressing the occurrence of subsequent cataract. Has proposed a method for suppressing subsequent cataracts (see Patent Document 3).
JP-A-9-291040 Japanese translation of PCT publication No. 2002-511315 JP 2006-238914 A Nishiki, et al., “Inhibitory effects of intraocular lenses on subsequent cataracts”, 15th European Intraocular Lens Society Abstract, 1997

  The method described in Patent Document 3 improves the adhesion of fibronectin, an adhesion protein, to the intraocular lens by surface modification of the intraocular lens, and improves the adhesion between the intraocular lens and lens epithelial cells via fibronectin. It is thought that it is possible to suppress post-cataracts that occur after surgery (for example, Hiroyuki Matsushima et al., “Active oxygen processing for acyclic intrarenal , JUNE 2006 903-1070), which has a certain effect on the suppression of the subsequent cataract, There is a growing demand for further improvements in effectiveness.

  Under such circumstances, the present invention provides a method for producing an intraocular lens capable of effectively suppressing a subsequent cataract that occurs after insertion of the intraocular lens, and an intraocular lens produced by the method. It is intended to do.

  As a result of intensive studies on the method for suppressing subsequent cataracts, the present inventors have surprisingly performed surface modification treatment on the intraocular lens material, and then brought it into contact with a polar medium, so that the intraocular lens It has been found that the adhesion with epithelial cells in the posterior capsule portion is effectively increased, and that a good post-cataract suppressing effect is exhibited, and the present invention has been completed based on this finding.

That is, the present invention
(1) A method for producing an intraocular lens, wherein the intraocular lens material is subjected to a surface modification treatment and then brought into contact with a polar medium;
(2) The method for producing an intraocular lens according to (1), wherein the polar medium contains one or more selected from water, methanol, and ethanol,
(3) The method for producing an intraocular lens according to (1) or (2), wherein the surface modification treatment is plasma treatment or ultraviolet treatment.
(4) The method for producing an intraocular lens according to the above (1) or (2), wherein the surface modification treatment is an active oxygen treatment,
(5) The method for producing an intraocular lens according to any one of the above (1) to (4), wherein the intraocular lens has an optical part made of a soft acrylic material.
(6) An intraocular lens manufactured by the method according to any one of (1) to (5) above, and (7) a surface disposed on at least the posterior capsule side is surface-modified. Thus, the intraocular lens according to the above (6) is provided.

According to the present invention, after the surface modification treatment is performed on the intraocular lens material, the intraocular lens is produced by bringing the intraocular lens material into contact with the polar medium, thereby effectively improving the adhesion between the intraocular lens and the posterior capsule portion. Therefore, it is possible to effectively suppress posterior capsule opacity associated with migration and proliferation of lens epithelial cells.
Therefore, according to the present invention, it is possible to provide a method for easily producing an intraocular lens capable of effectively suppressing secondary cataracts, and to provide an intraocular lens produced by the method. it can.

  The method for producing an intraocular lens of the present invention is characterized in that the intraocular lens material is subjected to a surface modification treatment and then brought into contact with a polar medium.

  The intraocular lens material to be surface-modified has a shape corresponding to the obtained intraocular lens, and usually has an optical part and a support part. For example, the optical part and the support part are integrally molded. And a three-piece type in which the optical part and the support part are separately manufactured and then joined together.

  There are no particular restrictions on the constituent material of the optical part, and either a soft material or a hard material can be used.However, if a soft material is used, a foldable soft lens can be obtained and handled during treatment. Is more preferable. Examples of the skeleton component constituting the soft material and the hard material include a polymer containing a structural unit composed of an acrylic monomer as a main structural unit.

  Examples of the skeleton component constituting the soft material include 2-phenylethyl methacrylate, 3-phenylpropyl methacrylate, 2-phenoxyethyl methacrylate, 2-phenylethyl acrylate, 3-phenylpropyl acrylate, 2-phenoxyethyl acrylate, and ethyl acrylate. , N-propyl acrylate, isobutyl acrylate, isoamyl acrylate, hexyl acrylate, 2-hydroxy methacrylate, N-vinyl pyrrolidone, and the like. Can do.

  Examples of the skeleton component constituting the hard material include a polymer containing as a main constituent unit a constituent unit composed of one or more monomers selected from methyl methacrylate, ethyl methacrylate and the like.

  In the polymerization of each monomer constituting the skeleton component, a crosslinking agent may be blended as necessary. Examples of the crosslinking agent include ethylene glycol dimethacrylate (EDMA), diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, neodymium. Such as pentyl glycol diacrylate (NPGA), 1,4-butanediol dimethacrylate, 1,6-hexanediol dimethacrylate, benzoyl peroxide, di-tert-butyl peroxide, lauroyl peroxide, camphorquinone, benzoin methyl ether, etc. One or more selected from among them can be mentioned.

  The amount of the crosslinking agent used is preferably 0.3 to 7 parts by weight, particularly preferably 0.5 to 5 parts by weight, when the total amount of monomers constituting the skeleton component is 100 parts by weight. . If the amount of the crosslinking agent used is less than 0.3 parts by weight, the introduction effect is not sufficiently exerted, and if it exceeds 7 parts by weight, the crosslinking points increase and become brittle, resulting in a decrease in mechanical strength.

  Furthermore, when forming the constituent material of the optical part, an ultraviolet absorbing component may be blended. Examples of the ultraviolet absorbing component include 2- (2-hydroxy-3-tert-butyl-5-methylphenyl). Mention may be made of monomers having an ultraviolet absorbing function such as -5- (2-methacryloxyethyl) benzotriazole, and the amount used is 0. When the total amount of monomers constituting the skeleton component is 100 parts by weight. The amount is preferably 1 to 4 parts by weight, and particularly preferably 0.5 to 3 parts by weight. In addition, a yellow coloring component may be added to correct blue vision, and the yellow coloring component includes 4- (5-hydroxy-3-methyl-1-phenyl-4-pyrazolylmethyl) having a yellow chromophore. ) -3-methacrylamino-1-phenyl-2-pyrazolin-5-one and the like yellow reactive monomers.

  Examples of the polymerization means for each monomer include heat, light, and electron beam. Examples of the polymerization initiator include 2,2′-azobis (isobutronitrile) (AIBN), 2,2-azobis (4-methoxy-2,4-dimethylvaleronitrile), 2,2-azobis (2 , 4-dimethylvaleronitrile), 2,2-azobis (2-methylpropionitrile), 2,2-azobis (2-methylbutyronitrile) and the like, and bis (4-t-butyl) (Cyclohexyl) peroxy dicardate, benzoyl peroxide, 1,1,3,3-tetramethylbutyl hydroperoxide, t-hexyl hydroperoxide, t-butyl hydroperoxide, 3,5,5-trimethylhexanol peroxide Organic peroxides such as oxide can be mentioned, and the addition ratio of the polymerization initiator is the total amount of monomers constituting the skeleton component. In case of a 00-fold both parts, preferably from 0.1 to 2 parts by weight, and particularly preferably 0.2 to 1 parts by weight.

  There are no particular restrictions on the constituent material of the support part, and either the soft material or the hard material constituting the optical part can be used. However, when the support part is made of a hard material, the intraocular lens and the posterior capsule of the lens are used. It becomes possible to further improve the adhesiveness with the part. Specific examples of the constituent material of the support portion include one or more selected from polypropylene (PP), polymethyl methacrylate (PMMA), fluororesin (polyvinylidene fluoride), polyimide resin, and the like.

  In the method of the present invention, the method for producing the intraocular lens material to be surface-modified is not particularly limited, and a conventionally known method can be used.

  Specifically, (1) the optical part forming monomer is injected into the concave part of the plastic disk having the concave part made of the supporting part forming material, polymerized, and then cut into a predetermined shape and polished to obtain an intraocular lens. (2) The peripheral part of a rod-shaped plastic member made of an optical part forming material is filled with an acrylic monomer for forming a support part, polymerized, then cut into a predetermined shape and polished to obtain an intraocular lens. A manufacturing method, (3) a method of injecting a monomer into a resin mold having an intraocular lens-shaped space, and molding an optical part and a support part with the same material can be employed.

  In the method (1), polyalkyl methacrylate, fluororesin (polyvinylidene fluoride), polyimide resin, or the like is used as a material constituting the plastic disk having a recess made of a support portion forming material.

  Further, in the method (2), examples of the acrylic monomer for forming the support portion include monomers that form the polyalkyl methacrylate exemplified as the material constituting the plastic disk having the recesses in the method (1). be able to.

  In the method (3), examples of the monomer for forming the optical part and the support part include the monomers for synthesizing acrylic materials used as the soft material or the hard material exemplified as the optical part forming material. it can.

In the method of the present invention, the surface modification treatment is performed on the intraocular lens material.
The surface modification treatment method is not particularly limited as long as it is a method for improving the adhesion with lens epithelial cells on the surface of the intraocular lens material, and plasma treatment or treatment with ultraviolet rays is preferable, and corona discharge treatment, glow discharge treatment or UV / ozone treatment is more preferred. As the surface modification treatment method, treatment that generates active oxygen (active oxygen treatment) is particularly preferable. As the active oxygen treatment, ozone is generated from oxygen molecules by irradiating ultraviolet rays in an oxygen atmosphere, and then ozone. The ultraviolet ray / ozone treatment for generating active oxygen from is preferable. In the active oxygen treatment, it is considered that the surface treatment is performed by reacting the active oxygen species with the carbon atoms constituting the intraocular lens to generate a reactive functional group (—COO ⁻ ).

In the case of plasma processing, the current intensity and the distance to the object to be processed can be set as appropriate, and as the processing atmosphere gas, oxygen, air, CO ₂ , N ₂ , H ₂ , He, Ar, Ne, Kr, It can be suitably selected from gases consisting of Xe and the like.

  In the case of treatment with ultraviolet rays, a method of irradiating with ultraviolet light of 210 nm or less and ultraviolet / ozone treatment are preferable. In the case of the ultraviolet ray / ozone treatment method, the ultraviolet light (active light) used for the irradiation treatment has a wavelength of 150 to 300 nm. Light having two emission peaks in the region and having the function of decomposing oxygen molecules to generate ozone and decomposing the ozone to generate active oxygen species is preferable. Examples of ultraviolet light (active light) used for the irradiation treatment include light having emission peaks particularly in the wavelength region of 185 ± 5 nm and the wavelength region of 254 ± 5 nm.

  In the presence of oxygen, for example, by irradiating light having an emission peak in a wavelength region of 185 ± 5 nm and a wavelength region of 254 ± 5 nm, light in the wavelength region of 185 ± 5 nm first decomposes oxygen molecules and ozone is Then, it is considered that the light in the wavelength region of 254 ± 5 nm decomposes the ozone to generate active oxygen species having high energy. The active light can be generated by, for example, a low-pressure mercury lamp.

  The atmosphere at the time of irradiation with ultraviolet light (active light) is not particularly limited as long as it is an oxygen-containing atmosphere, and examples thereof include an oxygen atmosphere or an air atmosphere.

  The surface modification treatment is preferably performed on at least a surface disposed on the posterior capsule side of the intraocular lens optical unit. Further, in order to suppress the contraction of the anterior capsule incision edge, it is preferable to perform the treatment including the peripheral portion of the intraocular lens in the vicinity of the anterior capsule side. It is preferable to process the peripheral part without processing the central part.

  In this way, by surface-treating the optical part of the intraocular lens, the adhesion between the optical part and fibronectin, which is an adhesion protein, is increased, and the adhesion between the optical part and the posterior capsule part is improved via fibronectin. Therefore, it is considered that the movement and proliferation of the lens epithelial cells to the posterior lens capsule can be suppressed. This is due to the fact that Reijo J. et al. It is also supported by Linnola et al. That fibronectin plays an important role in the adhesion of the optic part of the intraocular lens to the sac (J Cataract Refraction Surg 2000; 26: 1792-1806). .

  In the method of the present invention, the intraocular lens material subjected to the surface modification treatment is brought into contact with a polar medium.

  Although it does not restrict | limit especially as a polar medium, What contains 1 or more types chosen from water, methanol, and ethanol is preferable, and what consists only of any 1 type chosen from water, methanol, and ethanol is more preferable. These media generally have the advantages that damage to the intraocular lens material is small, water is easy to obtain, disposal is easy after use, and alcohol is relatively easy to obtain. And since it is excellent in quick-drying, it has the advantage that the water stain | pollution | contamination after a contact process can be prevented.

  In the case of using water, there is no problem even with general tap water, but considering dirt and the like, those having a conductivity of 500 μS / cm or less are preferable, and those having a conductivity of 0.06 to 50 μS / cm are more preferable. Moreover, 5-9 are preferable and 6-8 are more preferable.

  The temperature of the polar medium is not particularly limited, but is preferably about room temperature (0 to 40 ° C.). When the temperature of the polar medium is about room temperature, the intraocular lens material can be easily handled in a stable state. In particular, when the intraocular lens material is made of an acrylic material, the grease (which is a phenomenon in which the transparency of the intraocular lens is impaired, is caused by bubbles in the medium caused by phase separation between the medium impregnated inside the lens material and the lens material. In view of this, it is preferable that the temperature of the polar medium is about room temperature.

  There is no particular limitation on the method of contacting the surface modified intraocular lens material with the polar medium, and there are a method of immersing the intraocular lens material in a polar solvent and a method of spraying the polar solvent onto the intraocular lens material. When the intraocular lens material is immersed in a polar solvent, ultrasonic vibration may be applied as desired. After the intraocular lens material and the polar medium are brought into contact with each other, a drying process may be appropriately performed. As the drying process, air blow or the like is preferable so that evaporation traces such as water are not generated. The drying temperature is preferably such that the shape of the obtained intraocular lens is not deformed. For example, it is preferably from room temperature to 70 ° C, and more preferably from room temperature (0 to 40 ° C) in consideration of handling properties. .

  In the intraocular lens manufacturing process, when the surface of the optical part is modified by plasma treatment or the like, it is usually performed so that dirt is not attached and the dirt is attached in order to finish a uniform modified surface. In the case where there is a possibility of this, the surface of the intraocular lens has been cleaned before the surface modification. On the other hand, the method of the present invention is an eye obtained by bringing the intraocular lens material into contact with the polar medium after subjecting the intraocular lens material to surface modification treatment, contrary to the above prior art. In the inner lens, the adhesiveness between the optical part and the epithelial cells in the posterior capsule of the lens can be improved, and the subsequent cataract can be effectively suppressed.

Next, the intraocular lens of the present invention will be described.
The intraocular lens of the present invention is manufactured by the method of the present invention, and the specific embodiment of the method of the present invention is as described above.

  EXAMPLES Next, although an Example demonstrates this invention further in detail, this invention is not limited at all by these examples.

  In the following examples and comparative examples, the adhesion of lens epithelial cells and the inhibitory effect on secondary cataracts were evaluated by the following methods.

(1) Adhesiveness of lens epithelial cells Lens epithelial cells were cultured in MEM (Minimum Essential Medium) containing 10% FBS (fetal calf serum), 37 ° C., 5% CO ₂ . Lens epithelial cells were cultured until confluent, and the cell density was adjusted to 30000 cells / mL using a hemocytometer. As the lens epithelial cells, rabbit lens epithelial cells were used in the following Examples 1 to 3 and Comparative Examples 1 to 4, and human lens epithelial cells were used in Example 4 and Comparative Example 5.

On the test piece having the same shape as the intraocular lens obtained in each Example and Comparative Example and subjected to the same treatment, the culture solution after the adjustment was dropped, and the inside of the incubator (37 ° C., 5 ° % CO ₂ ) for 6 hours. Six hours later, 10% formaldehyde phosphate buffer was added to stop cell growth, rinsed lightly in PBS (phosphate buffered saline), and fixed in an appropriately sized dish for 12-24 hours. Thereafter, the stained lens epithelial cells were stained with hematoxylin and eosin (H / E staining), and observed and photographed using a living body microscope.

  Hematoxylin / eosin staining (H / E staining) is a staining method often used for observing tissue slices in histology, and hematoxylin is a blue-violet pigment. Specific examples include cell nucleus, bone tissue, part of cartilage tissue, serous component and the like. In contrast, eosin is a red to pink pigment, and the tissue that stains it is called eosin or acidophilic. Specifically, cytoplasm, soft tissue connective tissue, red blood cells, fibrin, endocrine granules, etc. Can be mentioned.

(2) Suppressive effect on secondary cataract From the preoperative stage, an 8-week-old white rabbit (approximately 2 kg) that had mydriasis with an eye drop (trade name “Midrin PTM” manufactured by Santen Pharmaceutical Co., Ltd.) was anesthetized and ultrasonically Emulsification was performed and a lens was inserted through the corneal incision wound.
Two weeks after the operation, the rabbit was euthanized, the eyeball was removed, and fixed with 10% by mass formalin. After dehydration, a paraffin section was prepared, and after deparaffinization, it was stained with hematoxylin and eosin, and the central part of the intraocular lens was observed and evaluated with a living microscope.

Example 1
As a monomer constituting the skeletal component of the intraocular lens, 2-phenylethyl acrylate (PEA), 1,4-bis (2-hydroxyethoxy) phenyl acrylate (HPEA), methyl methacrylate (MMA), trifluoro Ethyl methacrylate (TFEMA) was used to prepare the weight ratio shown in Table 1. In preparation, together with the monomer constituting the skeleton component, neopentyl glycol diacrylate (NPGA) as a crosslinking agent, and 2- (2-hydroxy-3-tert-butyl-5-methylphenyl)- 5- (2-Methacryloyloxyethyl) benzotriazole (T-150) as a yellow coloring component, 4- (5-hydroxy-3-methyl-1-phenyl-4-pyrazolylmethylene) -3-methacrylamino-1- Phenyl-2-pyralisone-5-one (HMPO) and 2,2′-azobis (isobutyronitrile) (AIBN) as a polymerization initiator were each used with respect to the total amount of skeletal component constituting monomers of the intraocular lens. , 4.5 parts by weight, 1.5 parts by weight, 0.03 parts by weight, 0.3 parts by weight, homogeneous by thoroughly stirring Obtained a mixed liquid.

This mixed solution is poured into a polypropylene mold composed of a pair of upper and lower molds, and is subjected to a predetermined temperature program under a pressure of 0.2 MPa / cm ^{3 in} a pressure polymerization furnace sufficiently purged with nitrogen. The temperature was raised from room temperature to 50 ° C. in 30 minutes, held for 12 hours, then heated to 100 ° C. in 300 minutes, subsequently raised to 120 ° C. in 60 minutes, held for 2 hours, and then lowered to room temperature. Polymerization was carried out, followed by drying at 120 ° C. under normal pressure for 18 hours. The obtained polymer is obtained by forming the front and back surfaces of the optical part and the support part by the inner surfaces of the upper mold and the lower mold, respectively. The polymer is milled to obtain side surfaces of the optical part and the support part. A one-piece intraocular lens material was obtained by forming a contour shape.

  The intraocular lens material is placed 10 mm below the low-pressure mercury lamp in the chamber of “I-UV / ozone cleaning device (OC-401212-A-T)” manufactured by Iwasaki Electric Co., Ltd. UV light / ozone treatment was performed by irradiating with active light for 90 seconds in the presence of.

  Next, after immersion treatment in distilled water (conductivity 5 μS / cm) for 5 minutes, the remaining water was removed by air blowing with clean air at room temperature to obtain an intraocular lens. The obtained intraocular lens was sterilized with ethylene oxide gas.

  In addition, by injecting the same mixed solution as that used for the preparation of the intraocular lens material into a polypropylene mold and processing under the same conditions as the preparation conditions for the intraocular lens material, a diameter of 14 mm and a thickness of A cylindrical polymer having a thickness of 1 mm was obtained. A cylindrical test piece was obtained by subjecting this cylindrical polymer to ultraviolet / ozone treatment, immersion treatment in water and sterilization treatment in the same manner as the treatment method for the intraocular lens material.

  The adhesion of rabbit lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the cylindrical test piece. In FIG. 1, the photograph in the column “Example 1” is a micrograph at the time of this evaluation. In this column, the cell nucleus stained in a deep blue-purple shape with an ellipse having a major axis of about several μm and the surroundings are shown. Lens epithelial cells with a pale pink stained cytoplasm are shown (a portion of the lens epithelial cells is surrounded by a square black border to clarify its outline). From the evaluation results shown in FIG. 1, it can be seen that the lens epithelial cells overlap and adhere to the surface of the intraocular lens obtained in this example at a very high density.

Example 2
The same intraocular lens material as used in Example 1 was subjected to UV / ozone treatment in the same manner as in Example 1, and then the ASONE “Ultrasonic Cleaning Device for 2 weeks” was used. Intraocular lenses were obtained by immersing in distilled water (conductivity 5 μS / cm) vibrated ultrasonically for 5 minutes and removing the remaining water by air blowing with clean air at room temperature. The obtained intraocular lens was sterilized with ethylene oxide gas.
In addition, the same cylindrical polymer as used in Example 1 is subjected to ultraviolet / ozone treatment, immersion in water, and sterilization in the same manner as the treatment method for the intraocular lens material. As a result, a cylindrical specimen was obtained.
The adhesion of rabbit lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the cylindrical test piece.
In FIG. 1, the photograph in the “Example 2” column is a micrograph at the time of this evaluation. In this column, the cell nucleus stained in a deep blue-purple shape with an ellipse having a major axis of about several μm and the circumference Lens epithelial cells with a pale pink stained cytoplasm are shown (a portion of the lens epithelial cells is surrounded by a square black border to clarify its outline). From the evaluation results shown in FIG. 1, it can be seen that the lens epithelial cells overlap and adhere to the surface of the intraocular lens obtained in this example at a very high density.

Comparative Example 1
The same intraocular lens material used in Example 1 was sterilized with ethylene oxide gas without subjecting it to ultraviolet / ozone treatment and immersion in water to obtain an intraocular lens.
Further, the same cylindrical polymer as used in Example 1 was subjected to neither the ultraviolet ray / ozone treatment nor the immersion treatment in water as a cylindrical test piece in this example.
The adhesion of the rabbit lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the cylindrical test piece.
In FIG. 1, the photograph in the “Comparative Example 1” column is a micrograph at the time of this evaluation. In this column, although the stained material that appears to be endocrine granules was confirmed, the lens epithelial cells can be slightly confirmed. (In FIG. 1, a part of the lens epithelial cells is indicated by a four-stroke black border).

Comparative Example 2
The same intraocular lens material as used in Example 1 was subjected to UV / ozone treatment in the same manner as in Example 1 and then sterilized with ethylene oxide gas without being immersed in water. The intraocular lens was obtained by processing.
In addition, the same cylindrical polymer as obtained in Example 1 was subjected to UV / ozone treatment and then not subjected to immersion treatment in water as a cylindrical test piece in this example. .
The adhesion of the rabbit lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the cylindrical test piece.
In FIG. 1, the photograph in the “Comparative Example 2” column is a micrograph at the time of this evaluation, and in this column, the lens epithelial cells were only slightly visible (in FIG. Part is indicated by a black square border).

Example 3
In the sample tube, 2-phenylethyl acrylate (PEA), 1,4-bis (2-hydroxyethoxy) phenyl acrylate (HPEA), and trifluoroethyl methacrylate (TFEMA) were used as monomers constituting the skeleton component. It prepared so that it might become a weight ratio shown in. In preparation, ethylene glycol dimethacrylate (EDMA) as a crosslinking agent, 2- (2-hydroxy-3-tert-butyl-5-methylphenyl) -5- ( 2-Methacryloyloxyethyl) benzotriazole (T-150) as yellow coloring component, 4- (5-hydroxy-3-methyl-1-phenyl-4-pyrazolylmethylene) -3-methacrylamino-1-phenyl-2 -Pyrarizone-5-one (HMPO), 2,2'-azobis (isobutyronitrile) (AIBN) as a polymerization initiator, 5 parts by weight, 1. 5 parts by weight, 0.02 parts by weight, and 0.4 parts by weight were blended and sufficiently stirred to obtain a homogeneous mixed solution.

This mixed solution was poured into a polypropylene mold consisting of a pair of upper and lower molds, and in a pressure polymerization furnace sufficiently purged with nitrogen, under a pressure of 0.2 MPa / cm ³ , a predetermined temperature program, The temperature was raised from room temperature to 45 ° C. in 60 minutes and held for 8 hours, then heated to 60 ° C. in 20 minutes and held for 2 hours, then heated to 80 ° C. in 60 minutes and held for 2 hours. After the temperature was raised to 100 ° C. for 6 minutes and held for 6 hours, the temperature was lowered to room temperature for polymerization, followed by drying at 120 ° C. under normal pressure for 18 hours. The obtained polymer is obtained by forming the front and back surfaces of the optical part and the support part by the inner surfaces of the upper mold and the lower mold, respectively. The polymer is milled to obtain side surfaces of the optical part and the support part. A one-piece intraocular lens material was obtained by forming a contour shape.

  Next, the intraocular lens material was subjected to ultraviolet / ozone treatment in the same manner as in Example 1, and then immersed in distilled water ultrasonically vibrated in the same manner as in Example 2 for 5 minutes. The water was removed by air blowing with clean air at room temperature to obtain an intraocular lens. The obtained intraocular lens was sterilized with ethylene oxide gas.

  In addition, by injecting the same mixed solution as that used for the preparation of the intraocular lens material into a polypropylene mold and processing under the same conditions as the preparation conditions for the intraocular lens material, a diameter of 14 mm and a thickness of A cylindrical polymer having a thickness of 1 mm was obtained. A cylindrical test piece was obtained by subjecting this cylindrical polymer to ultraviolet / ozone treatment, immersion treatment in water and sterilization treatment in the same manner as the treatment method for the intraocular lens material.

  The adhesion of rabbit lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the cylindrical test piece. In FIG. 2, the photograph in the column “Example 3” is a micrograph at the time of this evaluation, and in this column, the cell nucleus stained in a deep blue-purple shape with an ellipse having a major axis of about several μm and the surroundings are shown. Lens epithelial cells with a pale pink stained cytoplasm are shown (a portion of the lens epithelial cells is surrounded by a square black border to clarify its outline). From the evaluation results shown in FIG. 2, it can be seen that the lens epithelial cells overlap and adhere to the surface of the intraocular lens obtained in this example at a very high density.

Comparative Example 3
The same intraocular lens material as used in Example 3 was sterilized with ethylene oxide gas without performing ultraviolet / ozone treatment and immersion treatment in water to obtain an intraocular lens.
Further, the same cylindrical polymer as used in Example 3 was subjected to neither the ultraviolet ray / ozone treatment nor the immersion treatment in water as the cylindrical test piece in this example.
The adhesion of the rabbit lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the cylindrical test piece. In FIG. 2, the photograph in the “Comparative Example 3” column is a micrograph at the time of this evaluation, and in this column, the lens epithelial cells could be slightly confirmed (part of the lens epithelial cells in the figure). Is indicated by a black square border).

Comparative Example 4
The same intraocular lens material as used in Example 3 was subjected to UV / ozone treatment, and then sterilized with ethylene oxide gas without immersion in water. Obtained.
Further, the same cylindrical polymer as obtained in Example 3 was subjected to ultraviolet ray / ozone treatment, and was not subjected to immersion treatment in water, and was used as a cylindrical test piece in this example. .
The adhesion of the rabbit lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the cylindrical test piece. In FIG. 2, the photograph in the “Comparative Example 4” column is a micrograph at the time of this evaluation. From the same column, in Comparative Example 4, the adhesion density of the lens epithelial cells is lower than that in Example 3. It can be seen (in the figure, a part of the lens epithelial cells is indicated by a rectangular black frame).

Example 4
In a beaker, methyl methacrylate (MMA) as a skeleton component monomer of an intraocular lens and ethylene glycol dimethacrylate (EDMA) as a cross-linking agent were prepared so as to have the ratio shown in Table 1, and the total amount of MMA and EDMA On the other hand, 2- (2′-hydroxy-3′-tert-butyl-5′-methylphenyl) -5-chlorobenzotriazole (TINUV326) as an ultraviolet absorbing component and 4-[(1,5- Dihydro-3-methyl-5-oxo-1-phenyl-4H-pyrazole-4-ylidine) methyl] -2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one (Y-3G ), 2,2′-azobis (isobutyronitrile) (AIBN) as a polymerization initiator, 0.05 parts by weight and 0.01 parts by weight, respectively. , 0.05 part by weight was mixed and sufficiently stirred to obtain a homogeneous mixed solution.

  This mixed solution was poured into a polyethylene tube (inner diameter 15 mm × length 500 mm), sealed, and kept in water at 37.5 ° C. for 168 hours. Then, hold in a drying furnace at 40 ° C. for 1 hour, raise the temperature to 60 ° C. over 4 hours and hold for 9 hours, further raise the temperature to 90 ° C. over 6 hours and hold for 9 hours, then continue to 120 ° C. After heating up to 6 hours and holding for 9 hours, the temperature was lowered to 40 ° C. over 16 hours to obtain a rod-like polymer.

  The obtained rod-shaped polymer is sliced to a thickness of 5 mm to obtain a disk-shaped product, which is cut out with a milling machine, and cut and polished according to a conventional method to form a one-piece type intraocular lens material colored yellow. Obtained.

  An intraocular lens was obtained by subjecting the intraocular lens material to ultraviolet / ozone treatment, immersion in water, and sterilization treatment in the same manner as in Example 1.

  Further, the rod-shaped polymer used for the preparation of the intraocular lens material is processed to obtain a cylindrical polymer, and this columnar polymer is treated with ultraviolet rays / ozone in the same manner as the processing method for the intraocular lens material. A cylindrical test piece having a diameter of 15 mm and a thickness of 1 mm was obtained by performing immersion treatment in water and sterilization treatment.

  The adhesion of human lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the above cylindrical test piece.

  In FIG. 3, the photograph in the “Example 4” column is a micrograph at the time of this evaluation, and in this column, the cell nucleus stained in a deep blue-purple shape with an ellipse having a major axis of about several μm, and the surroundings. Lens epithelial cells with a pale pink stained cytoplasm are shown (a portion of the lens epithelial cells is surrounded by a square black border to clarify its outline). From the evaluation results shown in FIG. 3, it can be seen that the lens epithelial cells adhere to the surface of the intraocular lens obtained in this example at a high density.

Comparative Example 5
The same intraocular lens material used in Example 4 was subjected to UV / ozone treatment in the same manner as in Example 4, and then sterilized with ethylene oxide gas without being immersed in water. Thus, an intraocular lens was obtained.
The same cylindrical polymer as obtained in Example 4 was subjected to UV / ozone treatment and then not subjected to immersion treatment in water, which was used as a cylindrical test piece in this example. .
The adhesion of the human lens epithelial cells to the intraocular lens obtained in this example was evaluated by the above-described method using the cylindrical test piece.
In FIG. 3, the photograph in the “Comparative Example 5” column is a micrograph at the time of this evaluation. From this column, in Comparative Example 5, the adhesion density of the lens epithelial cells is lower than that in Example 5. It can be seen (in the figure, a part of the lens epithelial cells is indicated by a rectangular black frame).

In Example 1 and Example 2 in which the active light irradiation treatment and the immersion treatment in water were performed by comparing Example 1 and Example 2 with Comparative Example 1 and Comparative Example 2, adhesion of lens epithelial cells It can be seen that the property is effectively improved.
In addition, by comparing Example 3 with Comparative Example 3 and Comparative Example 4, even when the constituent materials of the intraocular lens material were different, the active light irradiation treatment and the immersion treatment in water were performed. In Example 3, it can be seen that the adhesion of the lens epithelial cells is effectively improved.
Similarly, even when Example 4 and Comparative Example 5 are compared, even when the constituent materials of the intraocular lens material are different, Example 4 in which the active light irradiation treatment and the immersion treatment in water were performed. Then, it turns out that the adhesiveness of a lens epithelial cell is improving effectively.

Example 5
When the intraocular lens obtained in Example 3 was implanted in a rabbit eye and the inhibitory effect on secondary cataract was evaluated by the above-described method, proliferation of lens epithelial cells that were extremely mild was confirmed at the center of the intraocular lens. However, it was confirmed that it was a single layer and was excellent in the effect of suppressing subsequent cataract. According to the biomicrograph, the thickness of the attached epithelial cells was about 18 μm.

Comparative Example 6
In the sample tube, a monomer liquid for forming a support [methyl methacrylate (MMA) as a skeleton component constituting monomer of an intraocular lens, ethylene glycol dimethacrylate (EDMA) as a cross-linking agent is prepared so as to have a ratio shown in Table 1, 1-anilino-4- (4-vinylbenzyl) aminoanthraquinone (AQ-1) as a blue reactive dye and 2,2′-azobis (isobutyronitrile) as a polymerization initiator with respect to the total amount of MMA and EDMA. ) (AIBN) each containing 0.06 parts by weight and 0.3 parts by weight] were added and sufficiently stirred to obtain a homogeneous mixed solution.

  This mixed solution is filled into a polyethylene tube, stoppered, and polymerized in water at 40 ° C. for 48 hours and further in a drying furnace at 90 ° C. for 12 hours to produce rod-shaped polymethyl methacrylate having a diameter of 18 mm and a height of 500 mm. A (PMMA) polymer was obtained.

  Subsequently, after making a hole with a radius of about 3 mm around the central axis of this rod-shaped polymer, it was sliced to a thickness of 5 mm to obtain a donut-shaped holed disk.

  Polymerization was performed by injecting a monomer solution for forming an optical part into a perforated part of the perforated disk in a polypropylene mold having a predetermined shape.

  As the monomer liquid for forming the optical part, 2-phenylethyl methacrylate (PEMA), n-butyl acrylate (n-BA), perfluorooctylethyloxypropylene methacrylate (BRM) is used as a monomer constituting the skeleton component, Prepared so as to have a weight ratio shown in Table 1, together with monomers constituting the skeleton component, ethylene glycol dimethacrylate (EDMA) as a crosslinking agent, and 2,2′-azobisisobutyronitrile as a polymerization initiator (AIBN), 2- (2-hydroxy-3-tert-butyl-5-methylphenyl) -5- (2-methacryloyloxyethyl) benzotriazole (T-150) as a UV-absorbing component, 2 parts by weight, 0.3 part by weight, 5 parts by weight were blended, was used as a homogeneous mixture by stirring thoroughly. The polymerization using the monomer liquid for forming an optical part is carried out in a predetermined temperature program, that is, the temperature is raised from room temperature to 60 ° C. in 30 minutes and held for 12 hours, and then heated to 80 ° C. in 60 minutes. Held for hours. Further, the temperature was raised to 100 ° C. in 60 minutes, held for 6 hours, and then lowered to room temperature.

  By the above process, a disk having a soft acrylic resin at the center and blue PMMA at the periphery was obtained.

  This disc is cut out with a milling machine, cut and polished in the usual way, and sterilized with ethylene oxide gas to make a one piece of soft acrylic resin with a blue PMMA support part with an optical part diameter of 6 mm (total length: 13 mm) A mold intraocular lens was produced.

  When the intraocular lens was implanted in a rabbit eye and the inhibitory effect of secondary cataract was confirmed by the above-described method, proliferation of the lens epithelial cells was confirmed at the center of the intraocular lens, and the proliferation layer compared to Example 5 Was apparently thick, and according to a biomicrograph, the thickness of the attached epithelial cells was about 116 μm.

Comparative Example 7
The same intraocular lens material used in Comparative Example 6 was subjected to UV / ozone treatment in the same manner as in Example 1 and then sterilized with ethylene oxide gas without being immersed in water. The intraocular lens was obtained by processing.
When the intraocular lens was implanted in a rabbit eye and confirmed the effect of inhibiting cataract in the same manner as in Comparative Example 6, the proliferation of lens epithelial cells was confirmed at the center of the intraocular lens. The proliferation layer was thick, and according to a biomicrograph, the thickness of the attached epithelial cells was about 35 μm.
In the intraocular lens of Example 5 in which the active light irradiation treatment and the immersion treatment in water were performed by comparing Example 5 with Comparative Example 6 and Comparative Example 7, the intraocular lens and the lens capsule It can be seen that the proliferative layer is thin and the effect of suppressing subsequent cataract is higher.

  ADVANTAGE OF THE INVENTION According to this invention, the method of manufacturing the intraocular lens which can suppress secondary cataract effectively can be provided, and the intraocular lens manufactured by this method can be provided.

It is a figure which compares the adhesiveness of the lens epithelial cell with respect to the intraocular lens in the Example and comparative example of this invention. It is a figure which compares the adhesiveness of the lens epithelial cell with respect to the intraocular lens in the Example and comparative example of this invention. It is a figure which compares the adhesiveness of the lens epithelial cell with respect to the intraocular lens in the Example and comparative example of this invention.

Claims (7)

  A method for producing an intraocular lens, comprising subjecting an intraocular lens material to a surface modification treatment and then contacting with a polar medium.   The method for producing an intraocular lens according to claim 1, wherein the polar medium contains one or more selected from water, methanol, and ethanol.   The method for producing an intraocular lens according to claim 1 or 2, wherein the surface modification treatment is plasma treatment or ultraviolet treatment.   The method for producing an intraocular lens according to claim 1, wherein the surface modification treatment is an active oxygen treatment.   The manufacturing method of the intraocular lens in any one of Claims 1-4 in which an intraocular lens has an optical part which consists of a soft acrylic material.   An intraocular lens manufactured by the method according to claim 1.   The intraocular lens according to claim 6, wherein at least a surface disposed on the posterior capsule side is subjected to surface modification treatment.

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