JP3324156B2 - contact lens - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a surface-modified contact lens, and more particularly to a contact lens having excellent hydrophilicity, stain resistance and biocompatibility on the surface of the contact lens.

[0002]

2. Description of the Related Art A contact lens includes a hard contact lens whose main component is methyl methacrylate;
-Soft contact lenses made of hydroxyethyl methacrylate are widely used. However, complications due to insufficient oxygen supply to the cornea have been pointed out for hard contact lenses made of methyl methacrylate, and contact lenses with higher oxygen permeability, which use organosilane compounds and fluorine-containing compounds as one component, are becoming mainstream. is there.
However, these lenses have the disadvantage of being easily soiled,
Contamination with lipids, proteins, cosmetics, dust and the like may cause fogging of the lens, resulting in reduced vision and eye damage. In addition, there is a disadvantage that the contact lens is difficult to clean as compared with the conventional hard contact lens.

A soft contact lens comprising 2-hydroxyethyl methacrylate as a main component has a very good wearing feeling compared to a hard contact lens due to its flexibility and high water content, and has a small burden on the cornea. Is increasing. However, on the other hand, microorganisms are easy to propagate due to high water content, and some methods such as boiling sterilization and sterilization with a peroxide agent are necessary, and if these are not performed properly, microorganisms can propagate on soft contact lenses. Soft contact lenses become cloudy, etc.
In addition, when this is worn, infections such as the cornea may be induced, which is a problem. In addition, the soft contact lens has a disadvantage that it is soft and easily broken, and in order to improve these, a soft contact lens to which glyceryl methacrylate, vinylpyrrolidone, butyl methacrylate, or the like is added has been used.

[0004] Depending on the state of the surface, contact lenses may be hydrophilic or hydrophobic. Generally, hydrophilic contact lenses have a better wearing feeling and less burden on the eyes. However, a hydrophilic surface has a drawback that dirt such as proteins easily adheres. Efforts have been made to improve these by using specific monomers to reduce fouling. For example, JP-A-61-
Japanese Patent No. 272716 discloses an improvement in stain resistance by including a fluorine-containing alkyl acrylate.
JP-A-140918 states that the inclusion of a fluoroalkyl methacrylate and 2,3-dihydroxypropyl methacrylate improves stain resistance. Also, Japanese Patent Application Laid-Open No. 63-40293 describes improvement of wettability by plasma treatment of a contact lens surface. Further, a method of imparting hydrophilicity by graft-polymerizing a hydrophilic monomer onto the surface of the plasma treatment is described in JP-A-2-220024. These all contribute to the modification of the contact lens surface.

[0005]

However, the methods of JP-A-61-272716 and JP-A-3-140918 do not essentially modify the contact lens surface. In the method disclosed in Japanese Patent Application Laid-Open No. 63-40293, the surface of the contact lens is simply made to be hydrophilic by plasma treatment. Disappears. Further, although the hydrophilicity is improved, there is a defect that the feeling of wearing and the stain resistance are not improved. JP-A-2-22
Although the method disclosed in Japanese Patent Publication No. 0024 or the like is very useful as a method for compensating the above-mentioned disadvantages, it is not satisfactory in terms of stain resistance and is not sufficiently satisfactory in terms of biocompatibility because the graft-polymerized hydrophilic monomer is an acrylamide-based monomer. Not.

Accordingly, the present invention has been accomplished by intensive studies in order to solve these problems. That is, an object of the present invention is to graft-polymerize a hydrophilic monomer, which is a biologically similar component, onto the surface of a contact lens,
An object of the present invention is to provide a contact lens which has excellent hydrophilicity and stain resistance, has a remarkably improved wearing feeling, and is further excellent in biocompatibility.

[0007]

In order to solve such a problem, the contact lens of the present invention comprises a copolymer containing fluoroalkyl (meth) acrylate and / or siloxanyl (meth) acrylate as a main component. At least the general formula (1) on the contact lens surface

[0008]

Embedded image

Wherein R is hydrogen, a carboxyl group or a carboxylate group, and R ₁ is hydrogen or a group having 1 to 4 carbon atoms.
R ₂ is an amine group having 2 to 6 carbon atoms, and n is 1
Represents an integer of from 5 to 5. ) Is graft-polymerized with a hydrophilic monomer containing the compound represented by the formula (1). The compound represented by the general formula (1) is characterized in that R ₂ is a choline group.

Further, the hydrophilic monomer may be acrylamide, N, or N, other than the compound represented by the general formula (1).
N′-dimethylacrylamide, N-isopropylacrylamide, 2-hydroxyethyl methacrylate, 2
-Hydroxyethyl acrylate, acrylic acid, N-vinylpyrrolidone, polyethylene glycol monomethacrylate, 2,3-dihydroxypropyl methacrylate, and at least one compound selected from vinyl acetate.

[0011]

[0012]

In order to achieve the object of the present invention, it is necessary to graft-polymerize a specific hydrophilic monomer onto the surface of a contact lens. Also, the hydrophilic monomer must be a bio-like component to ensure biocompatibility. Further, in order to ensure hydrophilicity, it is necessary to have a hydrophilic group, and it is necessary that dirt components such as proteins do not easily adhere.
Based on such knowledge, a component similar to a phospholipid which is a component of a biological membrane is most suitable.

Specific examples of the compound represented by the general formula (1), which is a component of the biological membrane, include 2-acryloyloxyethyl phosphorylcholine, 2-methacryloyloxyethyl phosphorylcholine, 2-fumaroyloxyethyl phosphorylcholine, and the like. No.

As the hydrophilic monomer in the present invention, such a biological membrane component may be used alone, or may be used together with another hydrophilic monomer. Such other hydrophilic monomers include acrylamide, N, N'-dimethylacrylamide, N-isopropylacrylamide,
2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, acrylic acid, N-vinylpyrrolidone, polyethylene glycol monomethacrylate, 2,
3-Dihydroxypropyl methacrylate and vinyl acetate are used, and one or a mixture of two or more of them is used.

The contact lens substrate used in the present invention is not particularly limited, but the effect is particularly high in a contact lens copolymer containing a highly hydrophobic component as a main component, and the fluoroalkyl (meth) acrylate and / or siloxanyl are used. It is particularly useful for contact lenses made of a copolymer containing (meth) acrylate as a main component.

The contact lens of the present invention can be obtained by graft-polymerizing the hydrophilic monomer onto the contact lens surface by a general method. That is, active species are generated by plasma treatment or corona discharge treatment on the surface of the contact lens in the air or oxygen atmosphere, and the treated contact lens is immersed in a hydrophilic monomer solution for graft polymerization. As the initiator at this time, for example, ammonium iron (II) sulfate (Mole salt), ammonium persulfate, or the like may be used. After graft polymerization,
Extraction of the unreacted hydrophilic monomer with water or the like is completed.

Since the contact lens according to the present invention is obtained by graft-polymerizing a hydrophilic monomer containing a compound represented by the general formula (1), which is a biologically similar component, as a main component on the surface of the contact lens, the contact lens has a markedly improved hydrophilicity. Has a contributing effect. In addition, the fluctuation of the graft chain significantly improves the resistance to contamination of proteins and the like, and furthermore, the compound represented by the general formula (1) is a component similar to a biological membrane, and therefore has reduced biocompatibility, particularly, cell adhesion. And is superior in suppressing fibrin adhesion. Therefore, a contamination-resistant contact lens having high safety and good biocompatibility can be provided.

[0018]

The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto.

(Example 1) A contact lens molded body composed of a copolymer of 60 parts by weight of methyl methacrylate, 30 parts by weight of tris (trimethylsiloxy) silylpropyl methacrylate, and 5 parts by weight of triethylene glycol dimethacrylate was placed at a distance of 2 cm between electrodes. It was installed between the electrodes of a corona discharge treatment device with a voltage between electrodes of 15 kV and a frequency of 60 Hz to perform discharge treatment. The treated contact lens was placed in an aqueous 8% by weight 2-methacryloyloxyethyl phosphorylcholine solution (containing 0.2% by weight of ammonium iron sulfate), replaced with nitrogen gas, sealed, and subjected to graft polymerization at 50 ° C. for 3 hours. The graft polymerized contact lens was immersed in warm pure water at 60 ° C. for 10 hours to remove a by-product polymer. When the contact angle of this contact lens was measured, it decreased from 92 ° before treatment to 24 °, indicating good hydrophilicity.

<Protein Adsorption Test> Contact lens 1 obtained by graft-polymerizing 5 ml of a protein solution obtained by dissolving 0.1 g of egg lysozyme in 100 ml of physiological saline.
Zero pieces were immersed and incubated at 37 ° C. for 24 hours. Twenty-four hours later, the contact lens was taken out, and the contact lens was rinsed with physiological saline, and the amount of lysozyme adsorbed was measured using a protein-assay kit (manufactured by Bio-Rad Inc.). As a result, lysozyme was below the detection limit, and almost no lysozyme was adsorbed.

<Platelet Adsorption Test> Platelet-rich plasma prepared from fresh rabbit blood was brought into contact with a graft-polymerized contact lens for 24 hours. After 24 hours of rinsing with a physiological saline solution, the surface of the contact lens was observed with a scanning electron microscope. As a result, fibrin generated by adsorbing and activating platelets was scarcely observed, indicating good biocompatibility.

Example 2 A contact lens molded article made of a copolymer of 90 parts by weight of 2-hydroxyethyl methacrylate and 10 parts by weight of glyceryl methacrylate was placed at a distance between electrodes of 2 cm, a voltage between electrodes of 20 kV, and a frequency of 50.
It was placed between the electrodes of a 00 Hz corona discharge treatment device to perform discharge treatment. The treated contact lens is placed in an aqueous solution (containing 0.2% by weight of ammonium iron sulfate) containing 8% by weight of 2-methacryloyloxyethyl phosphorylcholine and 1% by weight of N, N'-methylenebisacrylamide, and sealed after replacement with nitrogen gas. At 50 ° C. for 3 hours. The graft polymerized contact lens was immersed in warm pure water at 60 ° C. for 10 hours to remove a by-product polymer. When the contact angle of this contact lens was measured, it decreased from 58 ° before treatment to 25 °, indicating good hydrophilicity.

<Protein Adsorption Test> Evaluation was performed in the same manner as in Example 1. As a result, lysozyme was below the detection limit, and almost no lysozyme adsorption was observed.

<Platelet Adsorption Test> Evaluation was performed in the same manner as in Example 1. As a result, fibrin formed by adsorbing and activating platelets was scarcely observed, indicating good biocompatibility.

(Example 3) A contact lens molded body composed of a copolymer of 60 parts by weight of methyl methacrylate, 30 parts by weight of tris (trimethylsiloxy) silylpropyl methacrylate, and 5 parts by weight of triethylene glycol dimethacrylate was used. It was installed between the electrodes of a corona discharge treatment device having a voltage between electrodes of 20 kV and a frequency of 60 Hz, and discharge treatment was performed. The treated contact lens is placed in an aqueous solution containing 9% by weight of 2-fumaroyloxyethyl phosphorylcholine and 1% by weight of N, N'-methylenebisacrylamide (0.05% by weight of ammonium persulfate).
), And after purging with nitrogen gas, sealed and subjected to graft polymerization at 50 ° C for 3 hours. The graft polymerized contact lens was immersed in warm pure water at 60 ° C. for 10 hours to remove a by-product polymer. When the contact angle of this contact lens was measured, it decreased from 90 ° before treatment to 29 °, indicating good hydrophilicity.

<Protein Adsorption Test> Evaluation was performed in the same manner as in Example 1. As a result, lysozyme was below the detection limit, and lysozyme adsorption was hardly observed.

<Platelet Adsorption Test> The evaluation was performed in the same manner as in Example 1. As a result, fibrin formed by adsorbing and activating platelets was scarcely observed, indicating good biocompatibility.

Example 4 A contact lens molded body composed of a copolymer of 60 parts by weight of methyl methacrylate, 30 parts by weight of tris (trimethylsiloxy) silylpropyl methacrylate, and 5 parts by weight of triethylene glycol dimethacrylate was used. It was installed between the electrodes of a corona discharge treatment device having a voltage between electrodes of 20 kV and a frequency of 60 Hz, and discharge treatment was performed. The treated contact lens is placed in an aqueous solution (containing 0.05% by weight of ammonium persulfate) containing 6% by weight of 2-methacryloyloxyethyl phosphorylcholine, 2% by weight of acrylamide and 0.5% by weight of N, N′-methylenebisacrylamide, After purging with nitrogen gas, the mixture was sealed and subjected to graft polymerization at 50 ° C. for 3 hours. The graft polymerized contact lens was immersed in warm pure water at 60 ° C. for 10 hours to remove a by-product polymer. When the contact angle of this contact lens was measured, 92
° to 26 °, indicating good hydrophilicity.

<Protein Adsorption Test> Evaluation was performed in the same manner as in Example 1. As a result, lysozyme was below the detection limit, and lysozyme adsorption was hardly observed.

<Platelet Adsorption Test> Evaluation was performed in the same manner as in Example 1. As a result, fibrin formed by adsorbing and activating platelets was scarcely observed, indicating good biocompatibility.

COMPARATIVE EXAMPLE 1 A contact lens molded article comprising a copolymer of 60 parts by weight of methyl methacrylate, 30 parts by weight of tris (trimethylsiloxy) silylpropyl methacrylate, and 5 parts by weight of triethylene glycol dimethacrylate was placed at a distance of 2 cm between electrodes. It was installed between the electrodes of a corona discharge treatment device having a voltage between electrodes of 15 kV and a frequency of 60 Hz to perform discharge treatment. When the contact angle of this contact lens was measured, it was 36 ° from 91 ° before the treatment.
And showed good hydrophilicity.

<Protein Adsorption Test> Evaluation was performed in the same manner as in Example 1. As a result, about 0.2 μg of lysozyme was adsorbed per contact lens, and lysozyme adsorption was recognized.

<Platelet Adsorption Test> Evaluation was performed in the same manner as in Example 1. As a result, fibrin formed by adsorbing and activating platelets was observed on a part of the contact lens surface, and the platelet was activated. Did not show good biocompatibility.

(Comparative Example 2) A contact lens molded body composed of a copolymer of 60 parts by weight of methyl methacrylate, 30 parts by weight of tris (trimethylsiloxy) silylpropyl methacrylate, and 5 parts by weight of triethylene glycol dimethacrylate was used. It was installed between the electrodes of a corona discharge treatment device having a voltage between electrodes of 20 kV and a frequency of 60 Hz, and discharge treatment was performed. The treated contact lens is placed in an aqueous solution containing 9% by weight of acrylamide and 1% by weight of N, N'-methylenebisacrylamide (containing 0.3% by weight of ammonium persulfate), sealed after replacement with nitrogen gas, and sealed at 50 ° C. Graft polymerization was carried out for an hour. The graft polymerized contact lens was immersed in warm pure water at 60 ° C. for 10 hours to remove a by-product polymer. When the contact angle of this contact lens was measured, it decreased from 93 ° before treatment to 31 °, indicating good hydrophilicity.

<Protein Adsorption Test> Evaluation was performed in the same manner as in Example 1. As a result, about 0.05 μg of lysozyme was adsorbed per contact lens, and lysozyme was slightly adsorbed.

<Platelet Adsorption Test> The evaluation was performed in the same manner as in Example 1. As a result, fibrin generated by adsorbing and activating platelets was slightly observed on the surface of the contact lens, and some problems remained in the biocompatibility.

[0037]

The present invention provides a contact lens excellent in hydrophilicity, stain resistance, wearing feeling and biocompatibility because a hydrophilic monomer which is a bio-like component is graft-polymerized on the surface of the contact lens. be able to.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C08J ⁷ /00-7/18 C08F 265/06 G02C 7/04

Claims (3)

(57) [Claims] 1. A contact lens comprising a copolymer containing fluoroalkyl (meth) acrylate and / or siloxanyl (meth) acrylate as a main component, at least a compound represented by the following general formula (1): Wherein R is hydrogen, a carboxyl group or a carboxylic ester group, R ₁ is hydrogen or an alkyl group having 1 to 4 carbon atoms, R ₂ is an amine group having 2 to 6 carbon atoms, and n is an integer of 1 to 5 A contact lens obtained by graft-polymerizing a hydrophilic monomer containing a compound represented by the following formula: 2. The compound represented by the general formula (1)
_2. The contact lens according to claim 1, wherein ₂ is a choline group. 3. The method according to claim 1, wherein the hydrophilic monomer is a compound other than the compound represented by the general formula (1), acrylamide, N, N'-dimethylacrylamide, N-isopropylacrylamide, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, acrylic Acid, N-vinylpyrrolidone, polyethylene glycol monomethacrylate,
2. The contact lens according to claim 1, comprising at least one compound selected from 2,3-dihydroxypropyl methacrylate and vinyl acetate.