JP5680877B2 - Manufacturing method of intraocular lens and intraocular lens obtained by the method - Google Patents

Description

  The present invention relates to a method for manufacturing an intraocular lens in which the occurrence of grease is suppressed, and an intraocular lens obtained by the method.

  Conventionally, as one of the surgical methods for cataracts, a method of inserting an intraocular lens instead of the lens after extracting the lens is generally used.

  For such intraocular lenses, a monomer raw material that is a material of the intraocular lens is injected into a predetermined mold and polymerized and cured (cast molding method, hereinafter referred to as molding), or the monomer raw material is polymerized. The base material obtained by curing can be manufactured by a method of cutting into a shape of an intraocular lens (lathe cutting method). In an intraocular lens obtained by such a method, it has been reported that a plurality of small bright spots called “greasing” are generated due to voids formed in the lens base material after polymerization and curing.

  Accordingly, as disclosed in Patent Document 1, the present applicant impregnates a polymerizable monomer (substrate) again with a polymerizable monomer and then polymerizes (re-polymerizes) the monomer to suppress voids. I am doing so. Thus, it has been confirmed that the base material obtained by impregnating the monomer and repolymerizing can suppress the occurrence of grease.

JP 2004-89400 A

  Incidentally, the molding process is suitable for mass production for producing a plurality of intraocular lenses at a time, and is advantageous in that the material for forming the intraocular lens can be used efficiently. Furthermore, even an intraocular lens having a complicated shape (for example, a multifocal intraocular lens) can be easily manufactured. However, in order to reduce the grease of the intraocular lens created by molding, once the repolymerization is performed on the intraocular lens obtained by molding by the above-described conventional method, swelling or the like This makes it difficult to obtain a desired intraocular lens shape.

  In view of the above-described problems of the prior art, the present invention provides a method for producing an intraocular lens for accurately producing an intraocular lens while suppressing the occurrence of grease when producing an intraocular lens using molding. And providing an intraocular lens obtained by the method.

  In order to solve the above problems, the present invention is characterized by having the following configuration.

(1) In a method for manufacturing an intraocular lens using a mold that forms a shape of an optical part having a predetermined refractive power, a core material that is smaller than the mold even when impregnated with a polymerizable monomer is used. a first step of generating, the polymerizable monomer is impregnated to produce the impregnated core material, polymerizing the polymerizable monomer with the impregnated core material in a state of coexistence in the mold to said core member A second step in which the gap between the mold and the impregnated core material is filled with the polymerizable monomer and polymerized to form an outer periphery of the optical unit around the impregnated core material. And a second step of forming a shape .

  According to the present invention, when an intraocular lens is manufactured using mold processing, the production of an intraocular lens for obtaining an intraocular lens with high accuracy while suppressing occurrence of grease is obtained. Can be provided.

  In this embodiment, a monomer solution that is a raw material for a non-hydrous (hydrophobic) soft intraocular lens substrate is polymerized and cured, and then the substrate obtained by polymerization is placed in the monomer solution, Impregnation with monomer. Thereafter, re-polymerization is performed with the monomer soaked in the base material, thereby eliminating voids generated in the base material and suppressing generation of bright spots and the like.

  Such a non-hydrous soft intraocular lens base material can be obtained by blending one or several kinds of monomers to be a soft material. Moreover, in order to adjust the hardness (softness) of the base material obtained, it can also obtain by mix | blending the monomer used as a hard material suitably.

  Specific examples of such a soft material monomer (hereinafter referred to as soft monomer) include acrylic acid esters such as methyl acrylate, ethyl acrylate, propyl acrylate, 2-ethylhexyl acrylate, and butyl acrylate.

  Further, specific examples of the monomer that becomes a hard material (hereinafter referred to as a hard monomer) include methacrylic acid esters such as methyl methacrylate, ethyl methacrylate, propyl methacrylate, and butyl methacrylate.

  When obtaining a soft intraocular lens substrate using these soft monomers or a mixture of soft monomers and hard monomers, a crosslinking agent and a polymerization initiator are used as necessary. Specific examples of the crosslinking agent include dimethacrylic acid esters such as ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, and triethylene glycol dimethacrylate, and other materials that can be used as a crosslinking agent for forming an intraocular lens substrate. These crosslinking agents are used in the range of 0.5 to 10% by weight based on the total weight of the monomers as the base material.

  Examples of the polymerization initiator include materials that can be used as a polymerization initiator for forming an intraocular lens substrate such as azobisisobutyronitrile, azoisobutyrovaleronitrile, benzoin, and methyl orthobenzoylbenzoate. In addition to this, an ultraviolet absorbing material such as a benzotriazole-based material can be appropriately added to obtain an intraocular lens base material having an ultraviolet absorbing effect.

  Moreover, in this embodiment, the base material obtained using the monomer mentioned above, a crosslinking agent, and a polymerization initiator is again immersed in a monomer liquid mixture, and a monomer shall be impregnated in a base material. The monomer to be impregnated in the base material is used to fill a void generated in the base material. Accordingly, the monomer material has good biocompatibility and is not particularly limited as long as it is a polymerizable monomer material. However, in order not to change the physical characteristics of the obtained intraocular lens substrate as much as possible, the substrate It is preferable to use the monomer used in the synthesis of (if several types of monomers are mixed, the monomer mixture). A predetermined amount of the above-mentioned crosslinking agent and polymerization initiator is also added to the monomer mixture at this time.

  Next, a method for producing an intraocular lens using the monomers listed above will be described. In the present embodiment, the diffraction light (diffraction grating) formed on the base curve of the optical unit distributes incident light to a plurality of different focal points, so that a predetermined distance power and near-distance are applied to the subject's eye. A case where a diffractive multifocal intraocular lens giving a power is manufactured will be described as an example. For a detailed description of the diffractive multifocal intraocular lens, refer to, for example, JP 2000-511299 A.

  FIG. 2 shows a schematic diagram of an intraocular lens (multifocal intraocular lens) manufactured in the present embodiment. 2A is a front view, and FIG. 2B is a side view. In this embodiment, a three-piece type intraocular lens that is integrated after the optical unit 11 and the support unit 12 are separately formed is taken as an example, but as an intraocular lens manufactured by molding May be a one-piece type intraocular lens in which the optical part 11 and the support part 12 of the same material are integrally formed.

  The intraocular lens 10 has a predetermined refractive power, and when placed in the eye, an optical part 11 having a front surface 11a on the cornea side and a rear surface 11b on the retina side, and the optical part 11 in the eye of the patient's eye It consists of a pair of support part 12 for fixedly supporting by.

  On the front surface 11a of the optical unit 11, a diffraction region 15 is formed by a plurality of diffraction gratings 15a formed concentrically with the optical axis O as the center. One of incident light incident on the optical unit 11 by the diffraction grating 15a is formed. By diffracting the part, a near focus for near vision is obtained. In the present embodiment, the diffractive region 15 is formed over the entire area of the front surface 11a, and the addition generated by the diffractive region 15 is added to the refractive power obtained from the refractive index and the curvature of the optical unit 11. Thus, the intraocular lens 10 is provided with a plurality of focal points, a far focus (distance power) f2 for viewing a distance and a near focus (near frequency) f1 for viewing a distance.

  One end (base end) of the support portion 12 is joined to the optical portion side 11 and has a loop shape with the other end (tip end) as a free end. In addition, the support part 12 is formed with resin, such as PMMA (polymethylmethacrylate), a polypropylene, a polyimide.

  Here, the flowchart of the intraocular lens manufacturing method is shown in FIG. First, in step 101, a soft monomer, a hard monomer, and a crosslinking agent are put into a container at a predetermined ratio and mixed. Generally, the blending ratio of the soft monomer and the hard monomer for constituting these copolymers is appropriately selected according to the respective physical properties, but the hardness (the degree that the obtained intraocular lens is bent at the time of surgery ( The blending ratio may have any degree of softness.

  When the mixing of the soft monomer, the hard monomer, and the crosslinking agent is completed, a polymerization initiator is then added and mixed. This mixed solution is poured into a plate-shaped mold (not shown) and polymerized at a predetermined temperature. In this embodiment, the polymerization is carried out by sequentially placing each in a water bath at 60 ° C. and 90 ° C. for 24 hours. Thus, more stable polymerization can be performed by increasing the temperature stepwise. After a predetermined time (for example, about 48 hours) has passed from the start of polymerization in such a procedure, the flat substrate is taken out of the mold, and further placed in a vacuum oven at 95 ° C. for 24 hours to complete the polymerization.

  The flat base material obtained after the polymerization is cut with a known automatic lathe, and then a lens-shaped base material (hereinafter referred to as a core material) 10a that becomes a core material when molding is obtained. The core material 10a is formed so as to be slightly smaller than the shape of the completed intraocular lens 10 (optical unit 11). The shape of the core material 10a is preferably a lens shape close to the shape of the optical unit 11, but is not limited thereto. The core material 10a is for suppressing the grease generated in the optical part 11 to be finally formed by filling the space by the subsequent monomer impregnation treatment and repolymerization treatment, and is not limited to the lens shape. For example, a disk shape or the like may be used.

  In this embodiment, the core material 10a is formed by cutting. However, the present invention is not limited to this, and the core material 10a is molded using a mold slightly smaller than the mold used for final molding. It can also be formed by processing. Furthermore, when the core material 10a is placed in the mold, the curved surface of the core material that comes into contact with the bottom surface (inner wall) of the mold has the same or smaller curvature than that of the inner wall surface of the mold. Preferably it is formed. If the curved surface of the core material 10a is made in this way, contact between the mold center and the core material 10a can be avoided, and the surface shape near the center of the optical part 11 after completion may be formed sharply. There is.

  Next, in Step 102, the core material 10a is placed so as to be completely immersed in a monomer mixed solution having the same composition as described above, and is allowed to stand for a predetermined time to impregnate the core material 10a with the monomer. The impregnation time depends on the shape of the core material 10a and the surrounding environment (temperature, pressure, etc.), but may be a time that allows the monomer to sufficiently enter the voids generated in the core material 10a.

  The impregnation time is usually preferably 24 hours or more and 120 hours or less, more preferably 48 hours or more and 96 hours or less. When the impregnation time is less than 24 hours, it is difficult for the monomer to sufficiently enter the voids generated in the core material 10a. The impregnation time may be 120 hours or more, but the longer the impregnation time, the worse the production efficiency.

  Next, repolymerization is performed in step 103. The mold 100 includes a mold 100a having a recess 110a that matches the curved surface shape of the front surface 11a of the optical unit 11, and a mold 100b having a recess 110b that matches the curved surface shape of the rear surface 11b (see FIG. 4). When repolymerization is performed, the concave portions 110a and 110b of the mold dies 100a and 100b are overlapped so as to face each other, thereby forming the optical portion 11 having a desired shape. In addition, as a material of the mold 100, a metal or a resin is used. In the present embodiment, the monomer is polymerized and cured by heating. In the case of polymerization and curing with ultraviolet rays, a light transmissive resin that transmits ultraviolet rays is used.

  In addition, as a polymerization initiator in the case of polymerizing and curing with ultraviolet rays, tris (chloromethyl) triazine, 2,4-trichloromethyl- (4′-methoxystyryl) -6-triazine, 2- [2- (furan-2 -Yl) ethenyl] -4,6-bis (trichloromethyl) -S-triazine, triazine compounds such as 2,4,6-tris (trichloromethyl) -S-triazine, benzoin methyl ether, benzoin ethyl ether, benzoin Benzoin compounds such as isopropyl ether and benzoin butyl ether, diethoxyacetophenone, 4-phenoxydichloroacetophenone, 2-benzyl-2-dimethylamino-1- (4-morpholinophenyl) -butan-1-one, benzophenone, 2-Hydroxy-2-methylpropiof Acetophenone compounds such as 1-hydroxycyclohexyl phenyl ketone, 1-hydroxycyclohexyl acetophenone, thioxanthone compounds such as thioxanthone, 2-methylthioxanthone, 2,4-dimethylthioxanthone, 2-chlorothioxanthone, benzyldimethyl ketal, 2, 4,6-trimethylbenzoindiphenylphosphine oxide, isoamyl N, N-dimethylaminobenzoate, acylphosphine oxide, and the like can be used.

FIG. 3 is an explanatory diagram of the configuration of the mold 100a, FIG. 3 (a) is a top view, and FIG. 3 (b) is a cross-sectional view of the mold 100a as viewed from the direction of arrow AA.
A plurality of concentric grooves 115 for forming the diffraction grating 15a in the optical part 11 are formed in the concave part 110a of the mold 100a. The mold 100a is provided with a concave monomer supply unit 120 for filling the concave portion 110a and the concave portion 110b with the monomer during polymerization. The concave portion 110a is formed inside the monomer supply unit 120. Thus, when the monomer mixed solution is put into the monomer supply unit 120, the concave portion 100a is filled with the monomer mixed solution.

  Here, FIG. 4 shows an explanatory diagram of a production process in which repolymerization is performed by a molding method. Using the mold 100 as described above, first, as shown in FIG. 4A, the impregnated core material 10a is placed in the recess 110a of the mold 100a. Then, as shown in FIG. 4B, a monomer mixed solution having the same composition as the core material 10a is put into the monomer supply unit 120 so that the entire core material 10a is immersed in the monomer mixed solution. As a result, the monomer mixture enters from a slight gap formed between the recess 110a and the monomer supply unit 120, and the groove 115 is filled with the monomer mixture. Here, the core material 10a is first placed in the recess 110a and then the monomer mixed solution is put into the monomer supply unit 120. However, in the state where the monomer mixed solution is first put into the monomer supply unit 120, the core material 10a You may make it put.

  Next, as shown in FIG. 4 (c), the mold 110 is formed by fitting the recess 110a and the recess 110b. When the concave portion 110b is placed on the concave portion 110a, the monomer mixed solution in the monomer supply unit 120 fills the gap generated between the concave portion 110b and the core material 10a. Thereby, it will be in the state with which the space | gap which has arisen inside the mold 100 in which the core material 10a was set | placed was filled with the monomer without the clearance gap. Although illustration is omitted here, a thrust bearing or the like for preventing the rotation of the core material 10a may be attached to the mold 100 prepared as described above. If it does in this way, rotation of core material 10a will be prevented and an intraocular lens will be made with sufficient accuracy.

  Next, the mold 100 is heated in a dry oven for a predetermined time to perform second polymerization (repolymerization). At this time, the concentric diffraction grating 15 is transferred to the impregnated substrate 10a by polymerization of the monomer mixed solution filled in the groove 115 of the mold 100a. Thereafter, the polymerization is completely terminated by heating in a vacuum oven for a predetermined time. Thus, the base material once polymerized is impregnated with the monomer, and repolymerized with the mold 100, thereby closing the void generated in the base material in the first (first) polymerization, Decrease in transparency and generation of bright spots in the substrate are suppressed.

  When repolymerization is performed in the present embodiment, the monomer that has entered a slight gap between the recesses 110a and 110b and the core material 10a is also polymerized, and the periphery of the core material 10a forms the outer periphery of the optical unit 11. Will be covered with layers. Since this layer has not been subjected to a repolymerization treatment, voids are formed and greaseing is likely to occur. However, by making the core material 10a as close as possible to the shape of the optical part 11 and making the layer formed around the core material 11a as thin as possible, the occurrence of overall grease can be suppressed.

  When the two-stage polymerization operation as described above is completed, the optical unit 11 is removed from the mold 100 as shown in FIG. Then, the surface shape is adjusted by known polishing or the like. Thereafter, in step 104, if the three-piece intraocular lens 10 is used, the support part 12 is welded to the optical part 11 to complete the multifocal intraocular lens 10 in which a plurality of diffraction gratings 15 are formed ( (See FIG. 2).

  In the present embodiment, the case where a multifocal intraocular lens is manufactured has been described as an example. However, the present invention can also be applied to a case where a normal single focus lens is manufactured by molding. Thereby, generation | occurrence | production of greaseing is suppressed suitably and a highly accurate intraocular lens can be easily manufactured now.

  As described above, the re-polymerization of the core material 10a using the mold 100 suitably suppresses the grease that occurs in the intraocular lens, and makes it easy to form an intraocular lens having a complicated shape such as a multifocal lens. It becomes possible to manufacture with high accuracy.

  Moreover, in the manufacturing method of the intraocular lens of this embodiment, although the case where the core material 10a is formed by cutting a flat substrate impregnated in advance is described as an example, the present invention is not limited thereto. It is not a thing. As described above, the core material may be formed by molding. By using the mold processing, a plurality of core materials are produced at a time, so that the production efficiency is increased and the monomer for forming the core material is efficiently used.

  In this case, the size of the core material is determined after the impregnation in consideration of the shape change (for example, the core material is expanded by about 1.5 times by the impregnation). The core material is designed to be formed in a shape smaller than the size of the optical part 11 in a completed state. In other words, the shape of the mold die (not shown) for forming the core material is determined by considering the expansion coefficient after impregnation of the core material in advance.

  In addition, as a method of impregnating the core material formed by molding with the monomer mixed solution, the above-described mold 100 may be used in addition to the immersion in the monomer mixed solution as described above. In this case, the core material is placed on the mold 100a, and a monomer mixture liquid in an amount sufficient for impregnation of the core material is placed in the monomer supply unit 120 so that the core material is completely immersed. Thereby, the whole core material is impregnated with the monomer. And the optical part 11 is formed by performing superposition | polymerization of the obtained core material 10a by the method similar to the above.

Example 1
In Example 1, the degree of bright spot generation (greasing) of the intraocular lens sample obtained by the manufacturing method of the present embodiment described above was evaluated.
The raw materials for the base material were 162.0 parts by weight of ethylene glycol phenyl ether acrylate, 12.0 parts by weight of n-butyl acrylate, 119.1 parts by weight of n-butyl methacrylate, 6.0 parts by weight of 1,4 butanediol diacrylate, azo Isobutyronitrile was 0.3 parts by weight, and the monomer mixture to be impregnated was the same as the raw material of the substrate.

  The monomer mixture was polymerized (60 ° C., 24 hours water bath, 90 ° C., 24 hours dry oven heating, 95 ° C., 24 hours vacuum oven heating) by the above-described intraocular lens manufacturing method to obtain a flat plate material. . After that, taking into consideration the expansion rate due to impregnation (here, it is measured in advance to expand about 1.5 times), a core material (diameter: 3.9 mm, thickness 0) is obtained by cutting a flat plate material. 0.7 mm, and the radius of curvature R9.8 mm of the surface on which the diffraction grating is formed was obtained.

  Next, the core material was immersed in a monomer mixed solution made of the same raw material for 72 hours, and the voids generated in the core material were impregnated with the monomer. Then, the core material was taken out from the monomer mixture in a state where the monomer was sufficiently impregnated in the core material. At this time, the core material was expanded by impregnation, whereby an impregnated core material (diameter φ 6.0 mm, thickness 0.9 mm, radius of curvature R15 mm of the surface forming the diffraction grating) was obtained.

  Next, a core material impregnated in a mold die in which grooves for forming the above-described diffraction grating were formed was installed. At this time, the core material was placed so that the surface having the radius of curvature R15 and the surface on which the mold groove was formed coincided. Then, the mold mold (the above-described recesses 110a and 110b) was filled with a monomer mixed solution made of the same raw material as the core material and sealed.

  Then, after putting the mold type | mold provided with a core material in a 60 degree dry oven and hold | maintaining for 12 hours or more, it left still for 12 hours in a 95 degreeC vacuum oven, and completed 2nd superposition | polymerization. Then, the completed sample was removed from the mold.

  Next, the following operation was performed on the sample obtained as described above, and the degree of occurrence of grease (bright spot) was examined. First, pure water maintained at 50 ° C. was placed in a constant temperature water bath, and the sample obtained here was immersed for 2 hours. Thereafter, the sample was taken out together with the constant temperature water at room temperature, and immediately observed with time under a microscope. Observation of the change with time was observed immediately after taking out the sample from the thermostatic bath, one day later, and one week later.

(Comparative Example 1)
In Comparative Example 1, using the same material as in Example 1, the monomer mixture was injected into a known mold for an intraocular lens and polymerized once (60 ° C., 24 hours water bath, 90 ° C., 24 hours dry). The sample was completed by oven heating (95 ° C., vacuum oven heating for 24 hours).

(result)
FIG. 5 shows the observation results after one week of the sample prepared in Example 1, and FIG. 6 shows the observation results after one week of the sample prepared in Comparative Example 1. 5A and 6A are observation results at a magnification of 10 times, and FIGS. 5B and 6B are observation results at a magnification of 50 times. As can be seen from FIGS. 5 and 6, in Example 1, it was confirmed that the generation of bright spots in the range where repolymerization was performed after impregnation was suppressed. It was also confirmed that a diffraction grating was formed.

It is a flowchart of the intraocular lens manufacturing method. It is the schematic of an intraocular lens (multifocal intraocular lens). It is explanatory drawing of a structure of a mold type. It is explanatory drawing of the manufacturing process which performs repolymerization by a molding method. It is an observation result after one week of the sample created in Example 1. It is an observation result after one week of the sample created in Comparative Example 1.

DESCRIPTION OF SYMBOLS 10 Intraocular lens 10a Core material 15 Diffraction area 100 Mold type | mold 110a, 110b Concave part 120 Monomer supply part

Claims (5)

In a method of manufacturing an intraocular lens using a mold that forms a shape of an optical part having a predetermined refractive power ,
A first step of generating a core material having a shape smaller than that of the mold even when impregnated with a polymerizable monomer;
The polymerizable monomer is impregnated to produce the impregnated core material to the core material, a second step of polymerizing said polymerizable monomer and said impregnated core material in a state of coexistence in the mold The second step of forming the outer periphery of the optical part around the impregnated core material by polymerizing the polymerizable monomer in a gap formed between the mold die and the impregnated core material. When,
A method for producing an intraocular lens, comprising: In the intraocular lens manufacturing method of Claim 1 ,
The method of manufacturing an intraocular lens, wherein the core material is formed by molding using a mold mold smaller than the mold mold. In the intraocular lens manufacturing method of Claim 1,
The method of manufacturing an intraocular lens, wherein the core material is formed in a lens shape having a predetermined curved surface. In the intraocular lens manufacturing method in any one of Claims 1 thru | or 3,
A plurality of concentric grooves for forming a diffraction grating for giving a predetermined addition to the optical part of the intraocular lens are formed on the inner wall surface of the mold, and the eye is formed by the polymerization in the second step. A method for producing an intraocular lens, wherein a diffraction grating is formed on the inner lens. An intraocular lens obtained by the intraocular lens manufacturing method according to any one of claims 1 to 4.

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