JPH05277173A - Hydrous lens - Google Patents

Abstract

(57) [Summary] [Structure] At least N-vinyllactam, (meth)
A water-containing lens having a water content of 50% or more and 90% or less, which is a copolymer of an acrylic ester, vinyl alcohol and a crosslinking agent. [Effect] Since the water-containing lens of the present invention exhibits extremely excellent mechanical strength, it has excellent durability and shape stability even in a lens having a high water content, and further has excellent stain resistance to proteins. It can be suitably used as an eye lens such as a soft contact lens, an intraocular lens, and an artificial cornea.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a water-containing lens. More specifically, soft contact lenses, intraocular lenses,
The present invention relates to a water-containing lens for eyes such as an artificial cornea.

[0002]

2. Description of the Related Art As a water-containing lens, for example, a soft contact lens, which has conventionally been mainly composed of alkylene glycol monomethacrylate such as 2-hydroxyethyl methacrylate (2-HEMA), has a water content of 3%.
It was about 0 to 40%. However, in the soft contact lens containing 2-HEMA as a main component, a sufficient amount of oxygen required for corneal metabolism was not supplied from the atmosphere to the cornea through the lens. In order to improve this point, the following methods have been studied.

(1) A silicone rubber material having excellent oxygen permeability is used. (2) A copolymer of silicone, which is an oxygen permeable monomer, and a fluorine-containing monomer is used as a material. (3) Make the lens thin to increase oxygen permeability. (4) By increasing the water content of the lens, the oxygen permeability is increased by utilizing the behavior of water in the lens.

[0004]

In the above method (1), since the silicone rubber is water repellent, it is poorly compatible with tear fluid and easily attaches dirt, and may adhere to the cornea. was there. The above method (2) is a method mainly used in hard contact lenses,
In recent years, as seen in JP-A-3-179422,
Attempts have been made to use these monomers as one component of a material for soft contact lenses. In the method of (3) above, due to progress in processing technology, thinner lenses can be produced, and many thin soft contact lenses made of 2-HEMA have been commercially available. However, it was not possible to supply the cornea with a sufficient amount of oxygen required. In the method (4), a lens having a higher water content (water content) is obtained by copolymerizing a material such as N-vinylpyrrolidone or acrylic acid having a higher water content with 2-HEMA and other monomers. 50% or more) has been developed and some of them are already on the market. It can be said that these high water content soft contact lenses are physiologically safe materials for the eye because they can supply oxygen necessary for the cornea physiologically, but such high water content soft contact lenses have high water content. Therefore, the mechanical strength is low and sufficient durability is not obtained.
In particular, when the water content is 70% or more, the mechanical strength is remarkably lowered, so that there is a problem in using it as a material for contact lenses.

To solve this problem, Japanese Patent Laid-Open No. 53-7
As shown in 4049, a transparent and relatively high-strength material can be obtained by copolymerizing methyl methacrylate, which has been conventionally used as a material for hard contact lenses, with N-vinylpyrrolidone and a specific cross-linking agent. ing.
However, contact lenses using these materials have been pointed out to have drawbacks such as poor durability and low stain resistance against bacteria as compared with lenses using conventional HEMA as materials.

Further, as disclosed in Japanese Patent Laid-Open No. 63-23126, a contact lens containing polyvinyl alcohol having a high water content and a high strength as a main component has been studied.
Despite having a high water content of 80%, this material has high strength and excellent resistance to contamination with proteins and lipids, and was regarded as a promising material for soft contact lenses. It has poor boiling stability, which is an essential condition, and has not been put to practical use.

In order to improve boiling resistance, which is a drawback of this polyvinyl alcohol, various techniques for crosslinking polyvinyl alcohol have been studied. Japanese Patent Publication 47-9910
Also, in JP-A-50-115258, it has been attempted to crosslink polyvinyl alcohol with an acetal and hemiacetal bond, but these bonds are hydrolyzable and sufficient boiling stability is not obtained. Further, JP-A-62-32110 discloses a soft contact lens made of a polyvinyl alcohol derivative, in which a suspended (meth) acryloyl is cross-linked to the main chain of polyvinyl alcohol via a urethane bond, but this lens is also sufficient. It has not reached boiling stability.

As another attempt, an attempt has been made to copolymerize a hydrophobic monomer or polymer, which is considered to have high boiling stability, with polyvinyl alcohol. For example, JP-A-2-15233 discloses a high water content soft contact lens obtained by saponifying a copolymer of a (meth) acrylate polymer and a fatty acid vinyl ester. However, in this soft contact lens, since poly (fatty acid vinyl) that is not chemically bonded to the (meth) acrylate polymer remains in the polymer, there is much elution from the polymer, and the boiling stability is also poor. .

Therefore, an object of the present invention is to solve the above-mentioned drawbacks of the prior art, and to provide a water-containing lens which has a high strength even at a high water content and is excellent in boiling stability and stain resistance. .

[0010]

[Means for Solving the Problems] The inventors of the present invention have conducted extensive studies to achieve the above object and found that a copolymer composed of specific components has a water content, good gel strength, boiling stability, and stain resistance. It was found that the material has transparency and transparency, and completed the present invention.

That is, the present invention relates to a water-containing lens having a water content of 50% or more and 90% or less, which is a copolymer of at least N-vinyllactam, (meth) acrylic acid ester, vinyl alcohol and a crosslinking agent. is there.

Among the constituent components of the water-containing lens, N-vinyllactam is a component for imparting hydrophilicity to the lens. When the amount of N-vinyllactam used exceeds 60%,
It causes deterioration of durability, mechanical strength and stain resistance. It is preferably used at 20 to 60% by weight.

Examples of N-vinyllactam include N-vinyl-2-piperidone, N-vinyl-2-pyrrolidone,
N-vinyl-2-caprolactam, N-vinyl-3-methyl-2-pyrrolidone, N-vinyl-3-methyl-2-
Piperidone, N-vinyl-3-methyl-2-caprolactam, N-vinyl-4-methyl-2-pyrrolidone, N-
Vinyl-4-methyl-2-piperidone, N-vinyl-4
-Methyl-2-caprolactam, N-vinyl-5-methyl-2-pyrrolidone, N-vinyl-5-methyl-2-piperidone, N-vinyl-3-ethyl-2-pyrrolidone,
N-vinyl-4,5-dimethyl-2-pyrrolidone, N-
Vinyl-5,5-dimethyl-2-pyrrolidone, N-vinyl-3,3,5-trimethyl-2-pyrrolidone, N-vinyl-5-methyl-5-ethyl-2-pyrrolidone, N-
Vinyl-3,4,5-trimethyl-3-ethyl-2-pyrrolidone, N-vinyl-6-methyl-2-piperidone,
N-vinyl-6-ethyl-2-piperidone, N-vinyl-3,5-dimethyl-2-piperidone, N-vinyl-
4,4-dimethyl-2-piperidone, N-vinyl-7-
Methyl-2-caprolactam, N-vinyl-7-ethyl-2-caprolactam, N-vinyl-3,5-dimethyl-2-caprolactam, N-vinyl-4,6-dimethyl-2-caprolactam, N-vinyl- 3,5,7-trimethyl-2-caprolactam and the like are mentioned, and among these, N-vinyl-2-piperidone and N-vinyl-2-pyrrolidone are preferable. Moreover, these 1 type or 2 or more types of mixture can be used.

The (meth) acrylic acid ester is a component necessary for controlling the mechanical strength of the water-containing lens of the present invention and obtaining high strength. It also contributes to boiling resistance. Examples of (meth) acrylic acid ester used in the present invention include methyl methacrylate, methyl acrylate, ethyl methacrylate, ethyl acrylate, isopropyl methacrylate, isopropyl acrylate,
t-butyl methacrylate, t-butyl acrylate,
Isobutyl methacrylate, isobutyl acrylate,
t-amyl methacrylate, t-amyl acrylate,
2-ethylhexyl methacrylate, 2-ethylhexyl acrylate, lauryl methacrylate, lauryl acrylate, cyclohexyl methacrylate, cyclohexyl acrylate and the like can be mentioned. Among these, methyl methacrylate and cyclohexyl methacrylate having 4 to 10 carbon atoms are preferable.

In some cases, a hydrocarbon-containing (meth) acrylic acid ester having a fluorine substituent and / or a siloxane bond may be used as the (meth) acrylic acid ester. By using a fluorine-containing (meth) acrylic acid ester, a material with better stain resistance,
Further, by using (meth) acrylic acid ester having a siloxane bond, a material having higher oxygen permeability can be obtained.

Examples of the fluorine-containing substituent-containing (meth) acrylic acid ester include fluorinated alkyl (meth) acrylates and fluorinated hydroxyalkyl (meth) acrylates. Examples of fluorinated alkyl (meth) acrylates include, for example, 2,2,2-trifluoroethyl methacrylate, 2,2,2-trifluoroethyl acrylate, 2,2,3,3-tetrafluoropropyl methacrylate, 2 , 2,3,3-Tetrafluoropropyl acrylate, 2,2,3,3,3-pentafluoropropyl methacrylate, 2,2,3,3,3-
Pentafluoropropyl acrylate, 2,2,2-trifluoro-1-trifluoromethylethyl methacrylate, 2,2,2-trifluoro-1-trifluoromethylethyl acrylate, 2,2,3,3-tetrafluoro- t-amyl methacrylate, 2,2,3,3-tetrafluoro-t-amyl acrylate, 2,2,3
4,4,4-hexafluorobutyl methacrylate,
2,2,3,4,4,4-hexafluorobutyl acrylate, 2,2,3,4,4,4-hexafluoro-t
-Hexyl methacrylate, 2,2,3,4,4,4-
Hexafluoro-t-hexyl acrylate, 2,2
3,3,4,4,5,5-octafluoropentyl methacrylate, 2,2,3,3,4,4,5,5-octafluoropentyl acrylate, 2,3,4,5,5,5
5-hexafluoro-2,4-bis (trifluoromethyl) pentyl methacrylate, 2,3,4,5,5,5
-Hexafluoro-2,4-bis (trifluoromethyl) pentyl acrylate, 2,2,3,3,4,4
5,5,6,6,7,7-dodecafluoroheptyl methacrylate, 2,2,3,3,4,4,5,5,6
6,7,7-dodecafluoroheptyl acrylate, 2
-Hydroxy-4,4,5,5,6,7,7,7-octafluoro-6-trifluoromethylheptyl methacrylate, 2-hydroxy-4,4,5,5,6,7,
7,7-Octafluoro-6-trifluoromethylheptyl acrylate, 2-hydroxy-4,4,5,5,5
6,6,7,7,8,9,9,9-dodecafluoro-8
-Trifluoromethylnonyl methacrylate, 2-hydroxy-4,4,5,5,6,6,7,7,8,9,
9,9-Dodecafluoro-8-trifluoromethylnonyl acrylate, 2-hydroxy-4,4,5,5,5
6, 6, 7, 7, 8, 8, 9, 9, 10, 11, 11,
11-hexadecafluoro-10-trifluoromethylundecyl methacrylate, 2-hydroxy-4,4
5,5,6,6,7,7,8,8,9,9,10,1
Examples include 1,11,11-hexadecafluoro-10-trifluoromethylundecyl acrylate.

It is also possible to use itaconic acid (di or mono) esters, fumaric acid (di or mono) esters and styrene instead of the compounds mentioned. As these compounds, those having a fluorine substituent and / or a siloxane bond may be used. The above compounds may be used alone or in combination of two or more.

Although vinyl alcohol contributes to the water content, it also plays an important role in developing mechanical strength.
When the content of vinyl alcohol is 20% or less, the mechanical strength is lowered, and when the content is 60% or more, boiling resistance is insufficient. Further, by introducing vinyl alcohol into the polymer, stain resistance can be imparted to the polymer. This stain resistance increases as the content of vinyl alcohol in the polymer increases. From the above, it is preferable that the content of vinyl alcohol is 20 to 60%.

Since vinyl alcohol is unstable as a monomer, it is polymerized from an ester of vinyl alcohol and an organic acid (vinyl organic acid) as a raw material, and the resulting polymer is hydrolyzed to introduce vinyl alcohol into the polymer. You can do it. For example, N-vinylpyrrolidone,
A polymer obtained by polymerizing a composition containing a (meth) acrylic acid ester, an organic vinyl acid and a cross-linking agent, cut and polished into a lens shape, is a relatively strong alkaline solution such as an alcohol solution such as sodium hydroxide or potassium hydroxide. Hydrolysis can be carried out by immersing in and leaving at room temperature for several hours. In this case, the hydrolysis rate of the ester is controlled and the water content is adjusted by performing the reaction in a weakly alkaline alcohol solution using ammonium hydroxide or by changing the reaction conditions such as shortening the reaction time. It is possible. Furthermore, the organic acid vinyl can be hydrolyzed to vinyl alcohol even under an acid catalyst under the same conditions as the reaction conditions under an alkali catalyst.

Alcohols such as methanol and ethanol and 2,2,2-trifluoroethanol, 2,2,2 are used as alcohols in this saponification.
Fluoroalkyl alcohols such as 3,3-tetrafluoropropanol and the like can be mentioned. It is preferable to use methanol.

Generally, N-vinyl lactam and (meth) acrylic acid ester are said to have poor copolymerizability, but copolymerization of N-vinyl lactam and (meth) acrylic acid ester by adding vinyl organic acid. The higher the
Since the amount of unpolymerized residual monomer in the polymer is reduced, it is considered that the amount of elution from the polymer is reduced and the boiling stability is further improved.

Examples of the organic vinyl acid used include vinyl formate, vinyl acetate, vinyl pivalate, vinyl trifluoroacetate and the like. Of these, vinyl acetate and vinyl trifluoroacetate are preferable from the viewpoint of polymerizability. These may be used alone or in combination of two or more.

In addition to these monomers, 2 as a crosslinking agent
A functional or higher monomer can be added. For example, ethylene glycol dimethacrylate, ethylene glycol diacrylate, diethylene glycol dimethacrylate, diethylene glycol diacrylate, triethylene glycol dimethacrylate, triethylene glycol diacrylate, tetradecaethylene glycol dimethacrylate, tetradecaethylene glycol diacrylate, allyl methacrylate, allyl Acrylate, trimethylolpropane trimethacrylate, trimethylolpropane triacrylate, 1,3-butanediol dimethacrylate, 1,3-butanediol diacrylate, 1,4-butanediol dimethacrylate, 1,4-butanediol diacrylate, 1,6-
Hexanediol dimethacrylate, 1,6-hexanediol diacrylate, 1,9-nonanediol dimethacrylate, 1,9-nonanediol diacrylate, 1,10-decanediol dimethacrylate, 1,
10-decanediol diacrylate, neopentyl glycol dimethacrylate, neopentyl glycol diacrylate, 2,2′-bis [p- (γ-methacryloxy-β-hydroxypropoxy) phenyl] propane, methylenebismethacrylamide, methylenebisacrylamide , Vinyl methacrylate, triallyl cyanurate, dipentaerythritol hexaacrylate, polyethylene glycol # 400 dimethacrylate, polypropylene glycol # 400 dimethacrylate and the like. The cross-linking agent is usually used in 0.01 to 5.0% by weight of the total composition.

In addition to these essential monomers, other monomers may be added as long as the effects of the present invention are not impaired. For example, hydrophilic monomers such as dimethylmethacrylamide, dimethylacrylamide and 2-HEMA, and hydrophobic monomers such as methylmethacrylate, ethylmethacrylate, and styrenes.

Polymerization catalysts that can be used when copolymerizing the above composition include, for example, benzoyl peroxide,
2,2'-azobisisobutyronitrile, 2,2'-azobismethylisobutyrate, 2,2'-azobisdimethylvaleronitrile and the like can be mentioned. The addition amount of the polymerization catalyst is preferably 0.01 to 5% by weight based on the total mixture. Other than this, a polymerization method such as photopolymerization or radiation polymerization may be adopted.

In order to obtain a contact lens, the lens may be manufactured by cutting and polishing from the above polymer, or may be manufactured by directly polymerizing a mixture of the above monomers in a mold. good.

[0027]

EXAMPLES The present invention will now be described in detail with reference to examples, but the present invention is not limited thereto.

The physical properties of the lens were measured in the following manner. [Water Content] The weight (W ₁ ) of the lens in the dry state and the weight (W ₂ ) of the lens in the hydrated state were measured, and the water content (% by weight) was calculated by the following formula. Moisture content (% by weight) = [(W ₂ −W ₁ ) / W ₂ ] × 100 [Tensile test] Conducted by Shimadzu Autograph in water at 25 ° C. [Boiling resistance] After the lens was boiled in physiological saline for 100 hours, the diameter of the lens was measured. A sample having a dimensional change rate of 0.5% or less before and after boiling was defined as “good”. [Staining resistance] The lens was immersed in physiological saline containing 5% by weight of bovine serum γ-globulin and heated at 85 ° C for 2 hours. Next, the lens was thoroughly washed with physiological saline, and the amount of attached γ-globulin was quantified using a protein measurement kit manufactured by Bio-Rad.

Examples 1 to 12: Examples 1 to 1 shown in Table 1
10.0 g of each composition of 20 and 2,2 'as a polymerization catalyst
-0.2 g of azobis dimethyl valeronitrile was mixed and put into a polypropylene test tube, and after nitrogen substitution, it was sealed. This was immersed in a constant temperature water bath at 40 ° C. for 24 hours. Then, after immersing in a constant temperature water bath of 50 ° C. for 24 hours, it was transferred to a constant temperature bath of 60 ° C. for 5 hours, further left in a constant temperature bath of 80 ° C. for 2 hours, and finally left in a constant temperature bath of 100 ° C. for 1 hour. After cooling, the polymer was taken out from the test tube, cut, and cut to prepare a contact lens. Next, the lenses having the compositions of Examples 1 to 9 were immersed in a methanol solution of 0.1N sodium hydroxide, and the lenses having the compositions of Examples 10 to 12 were immersed in a trifluoroethanol solution, and the mixture was kept at room temperature for 2 hours. Saponification processing was performed by leaving it to stand. The lens taken out was neutralized with a dilute acetic acid aqueous solution and left in physiological saline for 1 day.

All the lenses retained a good lens shape, and had transparency that was also optically satisfactory. The results of measuring various physical properties of these lenses are shown in Table 1. Boil resistance was "good" for all examples. In the stain resistance test, the amount of γ-globulin attached was 0.51 (μg / cm ² ) in Example 7, 0.21 (μg / cm ² ) in Example 8, and 0.05 (μ in Example 9).
g / cm ² ).

Comparative Examples 1 to 4; Comparative Examples 1 to 4 shown in Table 1.
The composition was polymerized in the same manner as in Examples 1 to 12, and the polymer was cut to form a contact lens (saponification treatment was not performed). Table 1 shows the results of measuring various physical properties of these lenses. The amount of γ-globulin adhered in the stain resistance test was found in Comparative Example 3
It was 2.33 (μg / cm ² ).

From the above, it is clear that the Examples are superior in tensile strength and Young's modulus to the Comparative Examples having similar water contents, and have sufficient mechanical strength even for lenses having a high water content. Is. For example, in the lenses of Examples 1 to 3,
Tensile strength is 1 even in the high water content region of 80-90% water content
The value is 0 (kg / cm ² ) or more, and it is clear that the strength is remarkably improved as compared with Comparative Example 1. Further, also in the stain resistance test, the amount of γ-globulin adhered in the example is significantly lower than that in the comparative example, and it is clear that the stain resistance is also excellent.

[0033]

[Table 1]

[0034]

Since the water-containing lens of the present invention exhibits extremely excellent mechanical strength, it has excellent durability even for a lens having a high water content, and further has excellent stain resistance to proteins.

When the water-containing lens of the present invention is used as a soft contact lens, it has excellent mechanical strength.
It is expected that a soft contact lens with a higher water content can be manufactured than before, and that oxygen required for the cornea is sufficiently supplied. Further, since it is also excellent in resistance to contamination with proteins, it is expected that bacterial growth in the lens will be suppressed. As described above, the water-containing lens of the present invention is highly safe and can be used as a contact lens for a long-term continuous wear type. Further, since the hydrous lens of the present invention has high shape stability, it can be used as a soft contact lens for astigmatism correction, which has been considered difficult with conventional soft contact lenses.

The water-containing lens of the present invention can be suitably used as an ophthalmic lens such as an intraocular lens and an artificial cornea in addition to the soft contact lens.

Claims (1)

[Claims] 1. A water-containing lens having a water content of 50% or more and 90% or less, which is a copolymer containing at least N-vinyllactam, (meth) acrylic acid ester, vinyl alcohol and a crosslinking agent.