JP2659885B2 - Hydrous 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 hydrous 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 has conventionally been mainly composed of an alkylene glycol monomethacrylate such as 2-hydroxyethyl methacrylate (2-HEMA) as a main component, and has a water content of 3%.
It was about 0 to 40%. However, in a 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-based material having excellent oxygen permeability is used. (2) A copolymer of oxygen-permeable monomer silicone and fluorine-containing monomer is used as a material. (3) To make the lens thinner and enhance oxygen permeability. (4) By increasing the water content of the lens, the oxygen permeability is enhanced by utilizing the behavior of water in the lens.

[0004]

In the method (1), since the silicone rubber is water-repellent, it has poor compatibility with tears, easily adheres to dirt, and may adhere to the cornea. was there. The method (2) is a method mainly used for hard contact lenses,
In recent years, as seen in JP-A-3-179422,
Attempts have been made to use these monomers as a component of soft contact lens materials. According to the method (3), a thinner lens can be produced due to the progress of processing technology, and many thin soft contact lenses made of 2-HEMA are commercially available. However, it was not possible to supply a sufficient amount of oxygen required for the cornea. In the method (4), a lens having a higher water content (water content) is obtained by copolymerizing a material having a higher water content, such as N-vinylpyrrolidone and acrylic acid, with 2-HEMA and other monomers. (50% or more) have been developed and some are already commercially available. These high water content soft contact lenses can supply oxygen necessary for the cornea physiologically, so it can be said that they are materials that are more safe for the eyes, but such high water content soft contact lenses have a 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 reduced, so that there is a problem in using it as a material for contact lenses.

To solve this problem, Japanese Patent Laid-Open Publication No.
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 crosslinking agent. ing.
However, it has been pointed out that the contact lenses using these materials are inferior in durability and low in bacterial contamination resistance as compared with conventional lenses using HEMA as a material.

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

In order to improve the boiling stability, which is a drawback of polyvinyl alcohol, various techniques for crosslinking polyvinyl alcohol have been studied. Tokiko 47-6910
And JP-A-50-115258 attempt to crosslink polyvinyl alcohol with acetal and hemiacetal bonds, but these bonds are hydrolyzable, and sufficient boiling stability has not been obtained. Furthermore, Japanese Patent Application Laid-Open No. 62-32110 discloses a soft contact lens made of a polyvinyl alcohol derivative in which a main chain of polyvinyl alcohol is crosslinked with a heavy (meth) acryloyl via a urethane bond. Boiling stability has not been achieved.

As another attempt, attempts have been made to copolymerize polyvinyl alcohol with a hydrophobic monomer or polymer which is considered to have high boiling stability. 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, polyfatty acid vinyl that is not chemically bonded to the (meth) acrylate polymer remains in the polymer, so that a large amount of effluent from the polymer is present, so that the boiling resistance is poor. .

Accordingly, 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 high strength even at a high water content, and is excellent in boiling stability and stain resistance. .

[0010]

Means for Solving the Problems The present inventors have conducted intensive studies in order to achieve the above-mentioned object, and have found that a copolymer comprising a specific component has a water content, a good gel strength, a boiling stability, and a stain resistance. The inventors have found that they have transparency and transparency, and have completed the present invention.

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

N-vinyllactam is a component for imparting hydrophilicity to the lens among the constituent components of the hydrous lens. When the use amount of N-vinyl lactam exceeds 60%,
This results in reduced durability, mechanical strength and stain resistance. It is preferably used at 20 to 60% by weight.

Examples of N-vinyl lactam 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- Examples thereof include 3,5,7-trimethyl-2-caprolactam, and among them, N-vinyl-2-piperidone and N-vinyl-2-pyrrolidone are preferable. Further, one or a mixture of two or more of these can be used.

(Meth) acrylic acid ester is a component necessary for adjusting the mechanical strength of the water-containing lens of the present invention and obtaining high strength. It also contributes to boiling stability. Examples of the (meth) acrylate 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,
Examples thereof include 2-ethylhexyl methacrylate, 2-ethylhexyl acrylate, lauryl methacrylate, lauryl acrylate, cyclohexyl methacrylate, and cyclohexyl acrylate. Among them, methyl methacrylate or cyclohexyl methacrylate having 4 to 10 carbon atoms is preferable.

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

Examples of the (meth) acrylic acid ester containing a fluorine substituent include alkyl (meth) acrylates and hydroxyalkyl (meth) acrylates. Examples of the fluorinated alkyl (meth) acrylate include, for example, 2,2,2-trifluoroethyl methacrylate, 2,2,2-trifluoroethyl acrylate, 2,2,3,3-tetrafluoropropyl methacrylate, , 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-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,
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
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 thereof include 1,11,11-hexadecafluoro-10-trifluoromethylundecyl acrylate.

Instead of the above compounds, itaconic acid (di or mono) ester, fumaric acid (di or mono) ester and styrene can be used. As these compounds, those having a fluorine substituent and / or a siloxane bond may be used. The above compounds may be used singly or as a mixture of two or more.

Although vinyl alcohol also 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 reduced, and when the content is 60% or more, boiling stability is lacking. Further, by introducing vinyl alcohol into the polymer, stain resistance can be imparted to the polymer. This stain resistance improves as the content of vinyl alcohol in the polymer increases. From the above, the content of vinyl alcohol is preferably 20 to 60%.

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

Alcohols such as methanol and ethanol, and 2,2,2-trifluoroethanol, 2,2,2
And fluoroalkyl alcohols such as 3,3-tetrafluoropropanol. Preferably, methanol is used.

Generally, N-vinyl lactam and (meth) acrylate are considered to have poor copolymerizability. However, copolymerization of N-vinyl lactam and (meth) acrylate by adding an organic acid vinyl is considered. Nature,
It is considered that since the unpolymerized residual monomer in the polymer is reduced, the amount of eluted substances from the polymer is reduced, and the boiling resistance is further improved.

Examples of the organic acid vinyl used include vinyl formate, vinyl acetate, vinyl pivalate, and vinyl trifluoroacetate. Among them, vinyl acetate and vinyl trifluoroacetate are desirable from the viewpoint of polymerizability. One or more of these can be used.

In addition to these monomers, 2
More than functional monomers 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 crosslinking agent is usually used at 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 dimethyl methacrylamide, dimethylacrylamide, hydrophilic monomers such as 2-HEMA, and the like hydrophobic monomers scan Chile <br/> emissions, and the like.

As the polymerization catalyst which can be used for copolymerizing the above composition, for example, benzoyl peroxide,
Examples thereof include 2,2′-azobisisobutyronitrile, 2,2′-azobismethylisobutyrate, and 2,2′-azobisdimethylvaleronitrile. The addition amount of the polymerization catalyst is preferably 0.01 to 5% by weight based on the whole mixture. In addition, polymerization methods such as photopolymerization and radiation polymerization may be employed.

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

[0027]

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

The measurement of each physical property value of the lens was performed 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 equation. Water content (% by weight) = [(W ₂ −W ₁ ) / W ₂ ] × 100 [Tensile test] The test was carried out in water at 25 ° C. by Shimadzu Autograph. [Boiling resistance stability] After the lens was boiled in physiological saline for 100 hours, the lens diameter was measured. A sample whose dimensional change before and after boiling was 0.5% or less was defined as “good”. [Stain resistance] The lens was immersed in a physiological saline solution containing 5% by weight of bovine serum γ-globulin, and heated at 85 ° C for 2 hours. Next, the lens was sufficiently 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
And 10.0 g of each composition as a polymerization catalyst.
-0.2 g of azobisdimethyl valeronitrile was mixed, put into a polypropylene test tube, and sealed after nitrogen replacement. This was immersed in a constant temperature water bath at 40 ° C. for 24 hours. Then, after being immersed in a constant temperature water bath at 50 ° C. for 24 hours, it was transferred to a constant temperature bath at 60 ° C. for 5 hours, further left in a constant temperature bath at 80 ° C. for 2 hours, and finally left in a constant temperature bath at 100 ° C. for 1 hour. After cooling, the polymer was taken out of the test tube, cut, and cut to form a contact lens. Then, the lens of the composition of Examples 1-9, the methanol solution of 0.1N sodium hydroxide, lens composition of Example 10 to 12 were immersed in trifluoroethanol solution, 2 hours at room temperature Saponification treatment was performed by leaving it to stand. The removed lens was neutralized with a dilute acetic acid aqueous solution and left in physiological saline for one day.

All the lenses maintained good lens shapes, and had sufficiently satisfactory optically sufficient transparency. Table 1 shows the results of measuring various physical properties of these lenses. Boiling stability was "good" for all examples. In the stain resistance test, the attached amount of γ-globulin was 0.51 (μg / cm ² ) in Example 7, 0.21 (μg / cm ² ) in Example 8, and 0.05 (μg / cm ² ) in Example 9.
g / cm ² ).

Comparative Examples 1-4: Comparative Examples 1-4 shown in Table 1
Was polymerized in the same manner as in Examples 1 to 12, and this polymer was cut to produce a contact lens (no saponification treatment was performed). Table 1 shows the results of measuring various physical properties of these lenses. In the stain resistance test, the adhesion amount of γ-globulin was determined in Comparative Example 3.
Was 2.33 (μg / cm ² ).

From the above, it is apparent that the examples have superior tensile strength and Young's modulus as compared with the comparative example having the same moisture content, and that the lenses having a high moisture content have sufficient mechanical strength. It is. For example, in the lenses of Examples 1 to 3,
The 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 examples is significantly lower than the amount of adherence in the comparative example, and it is clear that the stain resistance is excellent.

[0033]

[Table 1]

[0034]

As described above, the water-containing lens of the present invention exhibits extremely excellent mechanical strength, so that even a lens having a high water content has excellent durability and also has excellent protein stain resistance.

When the water-containing lens of the present invention is used as a soft contact lens, it has excellent mechanical strength.
It is possible to manufacture a soft contact lens having a higher water content than ever before, and it is expected that oxygen required for the cornea will be sufficiently supplied. Furthermore, since it is excellent in resistance to contamination with proteins, it is expected that the growth of bacteria in the lens is suppressed. As described above, the water-containing lens of the present invention has high safety and can be used as a long-term continuous wearing contact lens. Further, since the water-containing lens of the present invention has high shape stability, it can be used as a soft contact lens for correcting astigmatism, which has been 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 a soft contact lens.

Claims (1)

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