JP2529538B2 - Contact lens and manufacturing method thereof - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for forming agglomerates of silk fibroin, a contact lens made from agglomerates of silk fibroin, and a method for producing the same.

[0002]

2. Description of the Related Art Conventional contact lens materials include
There are polymethylmethacrylate or various methacrylic acid ester-based copolymers. These are excellent in optical properties, mechanical strength, and machinability, and have been mainly used for hard contact lens materials, but they have poor oxygen permeability and cannot supply oxygen necessary for corneal metabolism through the lens. There wasn't.

In order to solve this problem, materials having excellent oxygen permeability such as siloxanyl methacrylate-based copolymers and copolymers containing siloxanyl methacrylate and fluoroalkyl methacrylate as essential components are used. Has been developed and put into practical use. However, although these materials have improved oxygen permeability, they have drawbacks that they have a poor hydrophilicity and poor water wettability, and therefore, they have a feeling of foreign matter during wearing and stains and the like tend to adhere. Therefore, it has been desired to develop a new contact lens material which is excellent in oxygen permeability and water wettability and is safe for the living body. Being safe for the living body is one of the necessary conditions as a material because contact lenses are medical devices.

[0004] Since insect-derived silk proteins, which are silk fibroins, have a primary structure similar to the amino acid composition of the living body, and further have excellent cell adhesion and growth properties on the silk protein membrane surface, and thus have good biocompatibility. As a safe material, it has been expected to be applied as a medical material and a biochemical material such as an enzyme-fixing membrane, a dialysis membrane, an artificial blood vessel, an artificial skin, an artificial cornea, a contact lens, and a medical capsule.

As an application to contact lenses, there has been disclosed a technique for hydrophilizing the surface of a contact lens with a silk fibroin film which takes advantage of the hydrophilic biochemical properties of silk protein (Japanese Patent Laid-Open No. 4-43921). Further, JP-A-5-313105 discloses a method for producing a contact lens from a silk fibroin solid material.

[0006]

In most of the conventional techniques for solidifying silk fibroin, a thin film-like product was obtained by drying and solidifying an aqueous solution in which silk fibroin was dissolved. For example, a silk film having a thickness of 10 to 300 μm is solidified by spreading a dilute aqueous solution of silk fibroin of about 1% by weight or less on a polyethylene film or the like and evaporating the sample water to dryness. However, homogeneous silk fibroin lumps are indispensable for preparing contact lens materials by the cutting and polishing method, and many thin silk fibroin membranes, which have been used in the past, were used to stack many pieces. In the case of the lump formed by the above method, an adhesive surface is formed at the interface between the films and a large optical strain is generated, which is inconvenient as a material for a contact lens which is an optical material.

Further, in Japanese Patent Laid-Open No. 5-313105, a silk fibroin solid substance is obtained. In this method, a silk fibroin aqueous solution as a sample is put in a polyethylene container having poor water vapor permeability and dried. In this container, the surface of the sample dries faster and the evaporation of water inside the sample and the bottom of the sample is blocked.Therefore, the solidification conditions differ depending on the sample site, resulting in uneven dryness of the sample. However, there is a drawback in that it is difficult to easily obtain a mechanically homogeneous silk fibroin solid.

Therefore, an object of the present invention is to provide a method for forming a silk fibroin lump, which is both optically and mechanically homogeneous and has very little optical distortion, a contact lens using the lump, and a method for producing a contact lens. To provide.

[0009]

Means for Solving the Problems As a result of intensive studies for solving the above-mentioned drawbacks, the present inventor first provided mechanically and optically homogeneous homogenous silk fibroin in order to provide a highly practical silk fibroin as a contact lens material. The present invention was accomplished by defining the concentration of an aqueous silk fibroin solution and appropriately controlling the evaporation rate of this aqueous solution, considering that the formation of such agglomerates of silk fibroin is an essential condition.

That is, according to the present invention, silk fibroin
An aqueous silk fibroin solution containing 0 to 45% by weight and substantially no electrolyte impurities is put into a forming container made of a water vapor permeable material, and water is evaporated while controlling the evaporation rate of the aqueous solution in the forming container. A method for forming a lump of silk fibroin characterized by removing and drying and solidifying.

Further, the present invention is a contact lens comprising the silk fibroin obtained by the above method.

The present invention also provides silk fibroin containing 20-
An aqueous silk fibroin solution containing 45% by weight and substantially no electrolyte impurities was placed in a forming container made of a water vapor permeable material, and the water was evaporated and removed while controlling the evaporation rate of the aqueous solution in the forming container. A method for producing a contact lens, which comprises drying and solidifying to form a lump of silk fibroin, and then cutting and polishing the lump to make a contact lens.

In the present invention, a silk fibroin aqueous solution is placed in a supple and thin sample container made of a water vapor permeable material, and the sample water is sequentially evaporated by blast drying from all directions of the sample container. , Forming an optically homogeneous mass of silk fibroin.

As the insect biopolymer which can be used in the present invention, not only silk fibroin derived from domestic silkworms but also silk fibroin derived from wild silkworms such as Tenji silkworm, tussah silkworm and Eri silkworm can be used. Also, take it out from the silkworm body,
It is also possible to use the liquid unmodified silk fibroin in the silk gland where silk proteins are accumulated, or the regenerated silk fibroin obtained by dialysis treatment after dissolving the cocoon thread, silk thread or silk product in a neutral salt solution. It is also possible to use.

In order to form a silk fibroin lump as the contact lens material of the present invention, first, 20 to 45% by weight, preferably 25 to 35% by weight of silk fibroin is contained, and substantially no electrolyte impurities are contained. An aqueous silk fibroin solution is prepared. Such an aqueous silk fibroin solution can be prepared by a conventionally known method.

That is, cocoon threads and raw threads are immersed in a mixed solution of 0.2% by weight Marcel soap and 0.05% by weight sodium carbonate and scoured at 98 ° C. for 1 hour to remove silk sericin on the fiber surface. . The silk fibroin fiber thus obtained is dissolved in a neutral calcium salt aqueous solution, a calcium nitrate aqueous solution, a lithium bromide aqueous solution, a lithium thiocyanate aqueous solution, or another neutral salt aqueous solution. You can That is, after the silk fibroin fiber was dissolved in these neutral salt aqueous solutions to obtain a silk fibroin aqueous solution, dialysis treatment was carried out with a dialysis membrane made of cellulose, and calcium ion, nitrate ion, lithium ion, thiocyanate contained in the aqueous solution were carried out. Ions, bromine ions, chlorine ions, etc. are completely removed from the aqueous solution.

As a result, a silk fibroin aqueous solution containing substantially no electrolyte impurities can be obtained. In addition, since silk fibroin, which is an insect biopolymer, has excellent physicochemical enveloping properties for low molecular weight substances, a coloring agent or an ultraviolet absorber, if necessary, can be added to the silk fibroin aqueous solution if necessary.
By adding a substance having a function such as a physiologically active substance or an antifungal agent and drying and solidifying, a silk fibroin lump containing these substances can be prepared.

The thus prepared aqueous silk fibroin solution containing no electrolyte impurities is placed in a container composed of a water vapor permeable membrane typified by a cellulose membrane, preferably 5 to
By blowing air drying at a temperature of 30 ° C., the water in the silk fibroin aqueous solution diluted during the dialysis treatment is sequentially evaporated and gradually concentrated, and the silk fibroin concentration is 20 to 45% by weight, preferably 25 to 35% by weight. An aqueous solution is obtained. In order to dry and solidify this aqueous solution to obtain a lump of silk fibroin, it is necessary to further perform blast drying at a temperature of 10 ° C. or higher to completely remove water. If the silk fibroin concentration is less than 20% by weight, it takes time to dry and solidify, and an optically and mechanically homogeneous product cannot be obtained. If it exceeds 45% by weight, the viscosity becomes high and it is difficult to control the drying and solidification. However, it is difficult to obtain a mechanically uniform product.

The material of the container for forming the silk fibroin agglomerate is not limited to the cellulose membrane, but porous polyteto
La fluoroethylene film, cellulose acetate film, even a film having fine pores as cellulose nitrate film does not leak water, can be used as a formation vessel be a film of water vapor transmitted easily porous.

When forming a silk lump, as the silk fibroin concentrate is dried, the volume of the concentrate in the forming container gradually decreases, and a space is formed in the upper part of the forming container. It is necessary to take measures to do so.

When the silk fibroin agglomerate is prepared by drying and solidifying the silk fibroin aqueous solution, the concentration of the aqueous solution is 1.0.
When a dilute solution of not more than 10% is used, a lump having a structure in which a random coil is predominant in X-ray diffraction is obtained. However, when 8 wt% or more of an aqueous silk fibroin solution is dried and solidified, the degree of crystallinity increases and a SILKI type crystal structure is obtained.

The silk fibroin agglomerates prepared and formed by the method of the present invention have a clear SILKI by X-ray diffraction analysis.
It has a type crystal structure and does not dissolve in water, but if necessary, it can be subjected to water insolubilization treatment with a conventionally known lower alcohol such as methyl alcohol or ethyl alcohol.

[0023]

The present invention will be described below with reference to examples. Example 1 30 g of refined silk fibroin fiber was divided into three 10 g portions, and 100 m of a 8.5 mol aqueous lithium bromide solution was prepared.
Into a triangular beaker, dissolve in a shaker at 55 ° C with stirring. After about 40 minutes, the completely dissolved silk fibroin aqueous solution was put into a cellulose dialysis membrane and dialyzed against tap water at a temperature of 20 ° C. for 5 days and then with pure water for 3 days to completely remove lithium ions and bromions. Remove.

At the time of dialysis, water is dipped in the cellulose dialysis membrane to dilute the concentration of the silk fibroin aqueous solution inside, and before the drying and solidification step, the speed is measured from the side surface of the cellulose dialysis membrane containing the silk fibroin aqueous solution. It is prepared by drying and concentrating in an aqueous solution of about 30% by weight while sending a wind of 6 m / sec.

The thus obtained silk fibroin aqueous solution having a concentration of about 30% by weight has a diameter of 27 mm and a height of 200 mm.
It is placed in a forming container made of a cellulose membrane, and tightly closed by tying the upper end opening with a suture so that air does not enter the forming container.

With this suspended on a stand, about 2
Air is blown from the side at a temperature of 5 ° C. to gradually increase the concentration of the aqueous solution in the container to obtain a lump.

As the sample aqueous solution evaporates, the volume of the upper part of the cellulose forming container decreases and the silk fibroin sequentially migrates to the lower side of the forming container. Therefore, silk fibroin is always contained in the forming container containing the aqueous solution. The top of the forming container must be wrapped with suture to fill it. When the sample concentration further increases and the volume decreases, this operation is repeated several times.

By this operation, a lump of silk fibroin was obtained after about 16 hours. A contact lens was prepared from this lump by a conventionally known cutting and polishing method.

Example 2 In the same manner as in Example 1, a 20% by weight silk fibroin solution was prepared. This solution was placed in a forming container similar to that used in Example 1 to form a silk fibroin lump in the same manner as in Example 1 to obtain a contact lens.

Example 3 In the same manner as in Example 1, a 45% by weight silk fibroin solution was prepared. This solution was placed in a forming container similar to that used in Example 1 to form a silk fibroin lump in the same manner as in Example 1 to obtain a contact lens.

Example 4 A 25% by weight silk fibroin solution was prepared in the same manner as in Example 1. This solution was placed in a forming container similar to that used in Example 1 to form a silk fibroin lump in the same manner as in Example 1 to obtain a contact lens.

Example 5 In the same manner as in Example 1, a 35% by weight silk fibroin solution was prepared. This solution was placed in a forming container similar to that used in Example 1 to form a silk fibroin lump in the same manner as in Example 1 to obtain a contact lens.

Comparative Example 1 A 30% by weight silk fibroin solution was prepared in the same manner as in Example 1. This solution has a diameter of 30 mm and a height of 50 m.
m polyethylene container and dried and solidified at 25 ° C. for 2 days with the upper part open.

By this operation, a silk fibroin lump was formed to obtain a contact lens.

Comparative Example 2 In the same manner as in Example 1, a 30% by weight silk fibroin solution was prepared. This solution was placed in the same forming container as that used in Example 1, and the concentration of the aqueous solution in the container was sequentially increased by the same method as in Example 1 to form a lump, to obtain a contact lens. In this case, as the water content in the cellulosic forming container was evaporated, the internal volume was decreased, and the silk fibroin was allowed to sequentially migrate to the lower side of the forming container and left as it was.

<Evaluation Method> Table 1 shows the results of evaluation as a contact lens material according to the following methods in connection with the above Examples and Comparative Examples. 1. Appearance As a block-shaped material suitable for processing contact lenses, visually check the transparency and degree of coloring of the block-shaped material and the suspended matter inside. 2. Properties The above block-shaped material is touched by hand, and its hardness is compared with that of the material of the comparative example. (The material does not peel off or collapse) 3. Hardness The above block-shaped material is measured by a Vickers hardness meter in a dry state (Dry). 4. Transparency Using the above block-shaped material as a disk having a thickness of about 0.2 mm, the light transmittance is measured in the visible region (380 to 780 nm). 5. Optical distortion Check the state of distortion inside the block with an optical distortion tester. <Judgment Criteria> Distortion is severe ... × Distortion is a little… △ Almost no distortion… ○ 6. Workability The above block-shaped material was processed by a conventional cutting and polishing method to prepare a contact lens, and evaluated according to the following criteria. 1) Machinability evaluation ... Ease of cutting during cutting <Judgment criteria> Lens processing is possible ... Good lens processing is not possible ... defective 2) Polishability evaluation ... Lens surface condition after polishing < Judgment criteria> The surface of the lens is extremely rough ...
× Lens surface is slightly rough ... △ Lens surface is almost not rough ... ○ 3) Evaluation in lens state …… Crack in lens state,
Check the presence of cracks <Judgment criteria> There are severe cracks and cracks in the lens ... × There are cracks and cracks in the lens ・ ・ ・ △ Almost no cracks or cracks in the lens ・ ・ ・ ○

[0037]

[Table 1]

[0038]

[Effect] The silk fibroin lump of the present invention was formed while controlling the evaporation rate of the silk fibroin aqueous solution in a container of water vapor permeable material while removing water isotropically from the entire sample surface area in the forming container. Therefore, it is optically and mechanically homogeneous.

Therefore, a method of forming a silk fibroin lump excellent in workability, which is free from cracks and cracks generated during the processing of contact lenses and has very little optical distortion,
A contact lens using the lump and a method for manufacturing a contact lens can be provided.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Norihiko Minoura 1-1, Higashi Tsukuba-shi, Ibaraki Institute of Industrial Science and Technology, Institute of Materials Technology (72) Inventor Yoshinori Kikuta 5--11 Segasaki, Urawa-shi, Saitama Examination Official Hitoshi Miura

Claims (9)

(57) [Claims] 1. An aqueous silk fibroin solution containing 20 to 45% by weight of silk fibroin and containing substantially no electrolyte impurities is placed in a forming container made of a water vapor permeable material, and the evaporation rate of the aqueous solution in the forming container is increased. While controlling
A method for forming a lump of silk fibroin, which comprises removing water by evaporation to dry and solidify. 2. The method for forming a silk fibroin lump according to claim 1, wherein the water vapor permeable material is a porous membrane. 3. The silk according to claim 1, wherein the water vapor permeable material is one selected from a cellulose membrane and a porous polytetrafluoroethylene membrane, a cellulose acetate membrane and a cellulose nitrate membrane. Fibroin mass formation method. 4. The method according to claim 1, wherein the step of evaporating and removing water to dry and solidify is carried out by isotropically evaporating and removing water by blast drying at a temperature of 10 ° C. or higher. Method of forming silk fibroin lumps. 5. A contact lens comprising a silk fibroin obtained by the method according to any one of claims 1 to 4. 6. A silk fibroin aqueous solution containing 20 to 45% by weight of silk fibroin and containing substantially no electrolyte impurities is placed in a forming container made of a water vapor permeable material, and the evaporation rate of the aqueous solution in the forming container is set. While controlling
A method for producing a contact lens, which comprises evaporating and removing water to dry and solidify to form a lump of silk fibroin, and then cutting and polishing the lump to form a contact lens. 7. The method of manufacturing a contact lens according to claim 6, wherein the water vapor permeable material is a porous film. 8. The contact according to claim 6, wherein the water vapor permeable material is one selected from a cellulose membrane and a porous polytetrafluoroethylene membrane, a cellulose acetate membrane and a cellulose nitrate membrane. Lens manufacturing method. 9. The method according to claim 6, wherein the step of evaporating and removing water to dry and solidify is carried out by isotropically evaporating and removing water by blast drying at a temperature of 10 ° C. or higher. Contact lens manufacturing method.