JP2012088525A - Contact lens care formulation and packaging solution - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide contact lens care formulation capable of providing the surface of a contact lens with durable surface lubricity and ameboid adhesion suppressing effect by a simple process; and to provide contact lens packaging solution using the same.SOLUTION: The contact lens care formulation according to the present invention comprises a solution that includes 0.01-2 wt./vol.% polymer with weight-average molecular weight of 5000-2000000, and the polymer includes a specific phosphorylcholine similar group-containing monomeric unit, a specific (meth)acrylamide derivative unit, and a specific hydrophobic-group-containing monomeric unit at specific ratios. The solution can be used for the contact lens packaging solution.

Description

  The present invention relates to a contact lens care preparation capable of imparting durable surface lubricity and an amoeba adhesion suppressing effect to a surface of a contact lens by a simple treatment, and a packaging solution used for sealing a contact lens in a container. .

In recent years, for the purpose of improving the wearing feeling of a soft contact lens, a method of incorporating a polymer substance that improves the lubricity of the surface of the soft contact lens into a care preparation or a packaging solution of the soft contact lens has been attempted. However, the improvement by the conventionally proposed polymer substance is not sufficient in durability, and the feeling of wearing is deteriorated particularly when worn all day, so that improvement is required.
Commercially available lens care preparations used during the storage of soft contact lenses generally have a disinfecting power to prevent the growth of fungi and amoeba during storage. However, as shown in Non-Patent Document 1, it is not effective for amoeba, and the occurrence of infectious diseases due to the attachment of amoeba is a social problem, and there is no sufficient solution. This is because since the material of the soft contact lens is hydrogel, it is difficult to impart durability such as lubricity and amoeba adhesion to the surface with durability.

By the way, a phosphorylcholine-like group-containing polymer is excellent in biocompatibility such as blood compatibility, complement inactivation, and non-adsorption of biological substances due to a phospholipid-like structure derived from a biological membrane. It is known to have excellent properties such as high hydrophilicity and high moisture retention. Therefore, research and development on the synthesis and use of polymers having the phosphorylcholine-like group for the purpose of developing bio-related materials are being actively conducted.
For example, Patent Document 1 proposes to use a polymer obtained by polymerizing a phosphorylcholine group-containing monomer and a hydrophobic alkyl group-containing monomer as a contact lens mounting solution. However, the polymer has a problem that the lubricity is insufficient, and the amoeba adhesion suppressing effect has not been investigated, and the amoeba adhesion suppressing effect is actually insufficient.
Patent Document 2 proposes a copolymer of a phosphorylcholine group-containing monomer and another hydrophilic monomer. However, since the copolymer has high hydrophilicity and flows out together with tears during wearing, it is difficult to obtain sufficient sustainability.
Patent Document 3 discloses a method of adding a copolymer of a phosphorylcholine group-containing monomer and butyl methacrylate to a contact lens packaging solution. However, the butyl group of the copolymer has a weak cohesive force as compared with a long-chain alkyl group, and there is little change in feel in an aqueous solution, so that the lens wearing feeling is not sufficiently improved.
Patent Document 4 discloses a method for obtaining an excellent detergency by using a copolymer of a phosphorylcholine group-containing monomer and an alkyl methacrylate as a contact lens cleaner. However, the surface lubricity of the lens and the amoeba adhesion suppression effect by the copolymer have not been investigated, and these effects were actually insufficient.

International Publication No. 02/15911 US Patent Application Publication No. 2008/0314767 US Patent Application Publication No. 2009/0100801 JP 2003-005136 A

Eye & Contact Lens 36 (1) 26-32, 2010

An object of the present invention is to provide a contact lens care preparation capable of imparting durable surface lubricity and an amoeba adhesion suppressing effect to the surface of a contact lens by a simple treatment.
Another object of the present invention is to provide a contact lens packaging solution capable of imparting durable surface lubricity and an amoeba adhesion suppressing effect to the surface of the contact lens.

（式中、Ｒ¹、Ｒ²及びＲ⁴はそれぞれ独立に水素原子又はメチル基を示す。Ｒ³はイソプロピル基、ｔ−ブチル基または２−ヒドロキシエチル基を示す。Ｒ⁵は炭素数１２〜２４の一価の炭化水素基を示す。ｎ１、ｎ２、ｎ３は構成単位のモル比を表し、ｎ１：ｎ２：ｎ３＝１００：１０〜４００：２〜５０を満たす）
また本発明によれば、上記コンタクトレンズ用ケア製剤からなるコンタクトレンズ用パッケージング溶液（以下、本発明のパッケージング溶液ということがある）が提供される。 As a result of intensive studies in view of the above problems, the present inventors have found that a copolymer obtained by polymerizing a specific phosphorylcholine-like group-containing monomer, a (meth) acrylamide derivative, and a hydrophobic group-containing monomer. The present invention has been completed with the knowledge that the coalescence is a material that is particularly excellent in surface lubricity and has an amoeba adhesion suppressing effect.
According to the present invention, a polymer having a structural unit represented by formulas (1a) to (1c) having a weight average molecular weight of 5,000 to 2,000,000 (hereinafter sometimes referred to as a PC polymer) is 0. A contact lens care preparation comprising a solution containing 0.01 to 2.0% by weight / volume% (hereinafter sometimes referred to as the care preparation of the present invention) is provided.

(In the formula, R ¹ , R ² and R ⁴ each independently represent a hydrogen atom or a methyl group. R ³ represents an isopropyl group, a t-butyl group or a 2-hydroxyethyl group. R ⁵ represents 12 to 12 carbon atoms. 24 represents a monovalent hydrocarbon group, n1, n2, and n3 represent the molar ratio of structural units, and satisfy n1: n2: n3 = 100: 10 to 400: 2 to 50)
Moreover, according to this invention, the packaging solution for contact lenses (henceforth the packaging solution of this invention) which consists of said care preparation for contact lenses is provided.

  The care preparation of the present invention comprises a PC polymer having a specific phosphorylcholine-like group-containing monomer unit, a (meth) acrylamide derivative unit, and a hydrophobic group-containing monomer unit at a specific ratio, Since the combined body has biocompatibility, hydrophilicity, and gel-forming ability, it is possible to impart durable surface lubricity and amoeba adhesion suppressing effect to the surface of the contact lens with a simple treatment. The care preparation of the present invention can be suitably used as a packaging solution when a contact lens such as a soft contact lens is sealed in a container and packaged.

Hereinafter, the present invention will be described in more detail.
The PC polymer used in the care preparation of the present invention has a weight average molecular weight of 5,000 to 2,000,000, preferably 100,000 to 1 having the structural units represented by the above formulas (1a) to (1c). , 500,000 polymers. When the weight average molecular weight is less than 5,000, the adhesion of the PC polymer to the contact lens surface is not sufficient, and durability may be inferior. When the weight average molecular weight exceeds 2,000,000, the viscosity during production is low. It may become too high and handling may be difficult.
The PC polymer may have other structural units other than the structural units represented by the formulas (1a) to (1c) as long as the effects of the present invention are not impaired.

In the formulas (1a) to (1c) constituting the PC polymer, R ¹ , R ² and R ⁴ each independently represent a hydrogen atom or a methyl group. R ³ represents an isopropyl group, a t-butyl group or a 2-hydroxyethyl group. R ⁵ represents a monovalent hydrocarbon group having 12 to 24 carbon atoms, such as a lauryl group, a stearyl group, or a behenyl group.
In the formulas (1a) to (1c), n1, n2, and n3 represent molar ratios of structural units, and satisfy n1: n2: n3 = 100: 10 to 400: 2 to 50. If n2 is larger than 400, the biocompatibility is not sufficient, and if it is less than 10, it may be difficult to improve the lens wearing feeling. On the other hand, if n3 is less than 2, the ability to form a physical cross-linked gel due to hydrophobic interaction is lowered, the adhesiveness with the contact lens surface is lowered, and the improvement of wearing feeling may not be sustained. When n3 exceeds 50, the hydrophilicity of the PC polymer decreases, which may cause a decrease in solubility in an aqueous solution and a decrease in surface hydrophilizing ability.

  The PC polymer is, for example, a phosphorylcholine-like group-containing monomer represented by formula (2) (hereinafter abbreviated as PC monomer), a (meth) acrylamide derivative represented by formula (3), It can be obtained by radical polymerization of a monomer composition containing a hydrophobic group-containing monomer represented by formula (4). The monomer composition may contain other polymerizable monomers that can be polymerized in addition to the above monomers.

式（２）中、Ｘは不飽和結合を有する重合性官能基を有する１価の有機基を示す。
式（３）及び式（４）中、Ｒ²〜Ｒ⁵は式（1b）及び（1c）のＲ²〜Ｒ⁵と同様な基もしくは原子を示す。
ＰＣ単量体としては、例えば、入手性が良いことから２−（（メタ）アクリロイルオキシ）エチル−２’−（トリメチルアンモニオ）エチルホスフェートが好ましく、さらに式（５）で示される２−（メタクリロイルオキシ）エチル−２’−（トリメチルアンモニオ）エチルホスフェート（以下、ＭＰＣと略す）が好ましく挙げられる。

In formula (2), X represents a monovalent organic group having a polymerizable functional group having an unsaturated bond.
Equation (3) and the formula (4), R ² ~R ⁵ shows the same groups or atoms as R ² to R ⁵ of the formula (1b) and (1c).
As the PC monomer, for example, 2-((meth) acryloyloxy) ethyl-2 ′-(trimethylammonio) ethyl phosphate is preferable because of its high availability. Further, 2-((meth) acryloyloxy) ethyl phosphate is preferable. Preferred is methacryloyloxy) ethyl-2 ′-(trimethylammonio) ethyl phosphate (hereinafter abbreviated as MPC).

  The PC monomer can be produced by a known method. For example, a compound obtained by reacting a hydroxyl group-containing polymerizable monomer and 2-bromoethyl phosphoryl dichloride disclosed in JP-A-54-63025 in the presence of a tertiary base is reacted with a tertiary amine. And a method of producing a cyclic compound by the reaction of a hydroxyl group-containing polymerizable monomer and a tubular phosphorus compound as shown in JP-A-58-154591 and the like, followed by a ring-opening reaction with a tertiary amine, etc. be able to.

Preferred examples of the (meth) acrylamide derivative represented by the formula (3) include N- (2-hydroxyethyl) acrylamide, N-isopropylacrylamide, and N- (t-butyl) acrylamide.
Examples of the hydrophobic monomer represented by the formula (4) include linear alkyl (meth) acrylates such as lauryl (meth) acrylate, stearyl (meth) acrylate, and behenyl methacrylate.

  Examples of other polymerizable monomers that can be used in the monomer composition include methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, and 2-ethylhexyl (meth) acrylate. Linear or branched alkyl (meth) acrylate; cyclic alkyl (meth) acrylate such as cyclohexyl (meth) acrylate; aromatic group-containing (meth) acrylate such as benzyl (meth) acrylate and phenoxyethyl (meth) acrylate; styrene, Styrene monomers such as methylstyrene and chloromethylstyrene; Vinyl ether monomers such as methyl vinyl ether and butyl vinyl ether; Vinyl ester monomers such as vinyl acetate and vinyl propionate; Polyethylene glycol (meth) acrylate, Polypropylene Hydrophilic hydroxyl group-containing (meth) acrylates such as N-glycol (meth) acrylate, N-vinylpyrrolidone, 2-hydroxyethyl (meth) acrylate, 2-hydroxybutyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate; Acid group-containing monomers such as (meth) acrylic acid, styrenesulfonic acid, (meth) acryloyloxyphosphonic acid; aminoethyl methacrylate, dimethylaminoethyl (meth) acrylate, N, N-dimethylaminopropyl (meth) acrylamide, etc. And an amino group-containing monomer; and cationic group-containing monomers such as 2-hydroxy-3- (meth) acryloyloxypropyltrimethylammonium chloride.

Other polymerizable monomers may affect the adhesion of the PC polymer to the contact lens surface depending on the type thereof, and therefore it is desirable to select the polymerizable monomer in consideration of its properties. Among other polymerizable monomers, 2-hydroxyethyl (meth) acrylate and 2-hydroxybutyl (meth) acrylate are used from the viewpoint of biocompatibility of the resulting PC polymer and adhesion to the contact lens surface. Preferred examples include hydroxyalkyl group-containing monomers such as, and cationic group-containing monomers such as (meth) acryloyloxyethyltrimethylammonium chloride and 2-hydroxy-3- (meth) acryloyloxypropyltrimethylammonium chloride.
When the other polymerizable monomer is blended with the monomer composition used for the production of the PC polymer, the blending ratio can be appropriately selected within a range that does not affect the effects of the present invention. When n1 shown by the above formula (1a) constituting the coalescence is 100, a molar ratio of 50 or less is preferable.

  For example, the PC polymer is produced by replacing the monomer composition with an inert gas such as nitrogen, carbon dioxide, argon or helium in the presence of a radical polymerization initiator, or radical polymerization in an atmosphere, for example, bulk polymerization. , Suspension polymerization, emulsion polymerization, solution polymerization and the like. From the viewpoint of purification, solution polymerization is preferable. The PC polymer can be purified by a general purification method such as a reprecipitation method, a dialysis method, or an ultrafiltration method.

  Examples of the radical polymerization initiator include 2,2-azobis (2-diaminopropyl) dihydrochloride and 2,2-azobis (2- (5-methyl-2-imidazolin-2-yl) propane) dihydrochloride. 4,4-azobis (4-cyanovaleric acid), 2,2-azobisisobutyramide dihydrate, 2,2-azobis (2,4-dimethylvaleronitrile), 2,2-azobisisobuty Azo radical polymerization initiators such as rhonitrile (AIBN); benzoyl peroxide, diisopropyl peroxydicarbonate, t-butylperoxy-2-ethylhexanoate, t-butylperoxypivalate, t-butylperoxydiisobutyrate, Organic such as lauroyl peroxide, t-butylperoxyneodecanoate, succinic peroxide (= succinyl peroxide) Oxide; ammonium persulfate, potassium persulfate, sulfates such as sodium persulfate. These radical polymerization initiators may be used alone or in a mixture. The usage-amount of a polymerization initiator is 0.001-10 mass parts normally with respect to 100 mass parts of monomer compositions, Preferably it is 0.01-5.0 mass parts.

  The production of the PC polymer can be carried out in the presence of a solvent. As the solvent, a solvent that dissolves the monomer composition and does not react can be used. Examples of the solvent include alcohol solvents such as water, methanol, ethanol, n-propanol, and isopropanol; ketone solvents such as acetone, methyl ethyl ketone, and diethyl ketone; ester solvents such as ethyl acetate; ethyl cellosolve, tetrahydrofuran, Examples include linear or cyclic ether solvents such as N-methylpyrrolidone; nitrogen-containing solvents such as acetonitrile and nitromethane. Preferably, water, alcohol or a mixed solvent thereof is used.

  In the care preparation of the present invention, the PC polymer is added to water, alcohol such as methanol, ethanol, isopropanol or a mixed solution thereof in an amount of 0.01 to 2.0 wt / vol% (hereinafter abbreviated as w / v%). It can be obtained by dissolving so that. If the concentration of the PC polymer is less than 0.01 w / v%, the amoeba adhesion suppression or the lubricating action is not sufficient, and if it exceeds 2.0 w / v%, the viscosity of the solution may be too high.

In the care preparation of the present invention, a buffering agent can be blended to adjust the pH. Examples of the buffer include citric acid, citrate, boric acid, borate, phosphoric acid, phosphate, tris (hydroxymethyl) aminomethane hydrochloride, or a mixture of two or more thereof.
In the care preparation of the present invention, the concentration when a buffering agent is blended is preferably 0.2 to 1.5 w / v%. If it is less than 0.2 w / v%, it is difficult to control the pH because the buffer capacity is low, and if it exceeds 1.5 w / v%, the solubility of other components may be impaired. The pH of the packaging solution used for packaging the contact lens is preferably about 6 to 9, and particularly preferably about 7.5. Therefore, when the care preparation of the present invention is used for the contact lens packaging solution, Is preferably adjusted to the above pH.

In order to control the osmotic pressure, the care preparation of the present invention contains, for example, an inorganic chloride such as sodium chloride, potassium chloride, magnesium chloride or a mixture of two or more thereof, and a polyol such as glycerin and saccharide. Can do.
As for the density | concentration in the case of mix | blending the said inorganic chloride and polyol with the care formulation of this invention, 0.1-1.5 w / v% is preferable. If it is less than 0.1 w / v% or exceeds 1.5 w / v%, the shape of the contact lens may change or the eye may be irritation.
The osmotic pressure of the care formulation of the present invention is preferably at an ophthalmologically acceptable level, for example in the range of at least about 200 mOsm / kg, preferably about 200-400 mOsm / kg.

In the care preparation of the present invention, a polymer other than the PC polymer can be blended in order to adjust the viscosity of the solution.
Examples of such a polymer include polyacrylic acid, acrylic acid-alkyl methacrylate copolymer, 2-hydroxyethyl methacrylate-methacrylic acid copolymer, polyanion, polyvinyl alcohol, hydroxyethyl cellulose, carboxymethyl cellulose, chitosan, and pullulan. Polysaccharides such as hyaluronic acid are preferred.
The blending amount when a polymer other than the PC polymer is blended with the care preparation of the present invention can be appropriately adjusted so as to have a desired viscosity.

In the care preparation of the present invention, other components that can be dissolved can be blended as necessary in addition to the above. For example, a preservative such as chlorhexidine gluconate, polyhexamethylene biguanide, benzalkonium chloride, paraben or a mixture of two or more of these can be blended.
The concentration when the preservative is blended with the care preparation of the present invention is preferably less than 0.1 w / v%. If it exceeds 0.1 w / v%, eye irritation may be increased.

The care preparation of the present invention can be used as it is as the packaging solution of the present invention used when sealing and packaging a contact lens such as a soft contact lens in a container, as well as a contact lens mounting solution, eye drops, etc. It can also be used as a blending component.
Here, the packaging solution is a solution sealed together with a contact lens in a packaging container such as a blister package. In general, since soft contact lenses are used in a state of being swollen with an aqueous solution, the lenses are sealed in a packaging container so that they can be used immediately after being swelled with an aqueous solution at the time of factory shipment.
The care preparation of the present invention or the packaging solution of the present invention can be made hydrophilic and highly lubricated by bringing it into contact with the surface of the contact lens. Has the effect of reducing pleasure. Furthermore, surface lubricity can be maintained and amoeba adhesion suppression can be provided.

  The type of contact lens targeted by the care preparation of the present invention or the packaging solution of the present invention is not limited, but is particularly useful for soft contact lenses. Examples of the soft contact lens include conventional hydrogel lenses obtained by polymerizing 2-hydroxyethyl methacrylate, methacrylic acid / 2-hydroxyethyl methacrylate, and swollen with an aqueous solution, 2-hydroxyethyl methacrylate, N- Examples include silicone hydrogel lenses obtained by copolymerizing a hydrophilic monomer such as vinylpyrrolidone or N, N-dimethylacrylamide with a siloxanyl group-containing monomer and swelling it with an aqueous solution.

  The care preparation of the present invention or the packaging solution of the present invention is applied to contact lenses, but can also be used in various fields such as various medical devices, cosmetics, and biochemical analyses. In particular, it is suitable for medical devices that require biocompatibility. Specifically, for example, it can be expected to be used for artificial blood vessels, catheters, dialyzers, blood filters, drug delivery carriers, wound dressings and the like.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited to these.
Various measurements in the examples were performed as follows.
<Molecular weight measurement>
5 mg of the obtained polymer was dissolved in 1 g of a methanol / chloroform mixed solvent (8/2, volume ratio) to prepare a sample solution. Other conditions are as follows.
Column: PLgel-mixed-C, standard material: polyethylene glycol, detection: parallax refractometer RI-8020 (manufactured by Tosoh Corporation), calculation of weight average molecular weight (Mw): molecular weight calculation program (GPC program for SC-8020), Flow rate 1 ml / min, sample solution injection volume: 100 μl, column temperature 40 ° C.
The number average molecular weight of the polymer is a value of the number average molecular weight measured by gel permeation chromatography (GPC) using polyethylene glycol as a standard sample. That is, the obtained aqueous polymer solution was diluted with distilled water to 0.5% by mass, and this solution was filtered through a 0.45 μm membrane filter and measured as a test solution.

In order to evaluate surface hydrophilicity, 2-hydroxyethyl methacrylate (HEMA) gel and silicone hydrogel were prepared by the following method.
Preparation of HEMA Gel A cell for HEMA gel polymerization was prepared by sandwiching a 1 mm thick fluororesin (PTFE) spacer with a polyethylene terephthalate (PET) film and further sandwiching with a glass plate from the outside. 100 parts by mass of HEMA, 0.3 part by mass of ethylene glycol dimethacrylate, 0.05 part by mass of AIBN were mixed, poured into a polymerization cell, and polymerized at 100 ° C. for 2 hours in a nitrogen atmosphere to obtain a transparent polymer. . After the polymer was swollen with ion-exchanged water, it was stored in a phosphate buffer solution (hereinafter abbreviated as ISO physiological saline) defined by ISO18369-3.
Preparation of Silicone Hydrogel A silicone hydrogel polymerization cell was prepared by sandwiching a 1 mm thick fluororesin (PTFE) spacer with a polyethylene terephthalate (PET) film and further sandwiching with a glass plate from the outside. 2-Methacryloyloxyethyl = 3-[(tristrimethylsiloxy) silyl] propyl = succinate 60 parts by mass, HEMA 20 parts by mass, N-vinylpyrrolidone 20 parts by mass, ethylene glycol dimethacrylate 0.3 parts by mass, AIBN 0.05 parts by mass Were poured into a polymerization cell and polymerized at 100 ° C. for 2 hours in a nitrogen atmosphere to obtain a transparent polymer. The polymer was swollen with ion-exchanged water and then stored in an abbreviated ISO physiological saline.

<Surface friction coefficient measurement>
Using a friction tester (trade name KES-SE, manufactured by Kato Tech Co., Ltd.), the surface friction coefficient of HEMA gel or silicone hydrogel was measured three times in physiological saline, and the average value was obtained.
Care preparation treatment conditions HEMA gel or silicone hydrogel was immersed in the obtained care preparation and allowed to stand overnight, and then the surface friction coefficient was measured.
Packaging Solution Treatment Conditions HEMA gel or silicone hydrogel was immersed in the obtained packaging solution, autoclaved at 120 ° C. for 15 minutes, and the surface friction coefficient was measured using a sample cooled to room temperature.
Measuring apparatus measurement conditions Sensitivity: H, probe speed 1 mm / sec, load: 25 g.
Judgment: Judgment was made by the following evaluation with reference to a state in which a polymer described later is not added (Comparative Example 2-1).
○: Friction coefficient is less than 1/10, Δ: Friction coefficient is 1/10 or more and less than 1/3, ×: Friction coefficient is 1/3 or more.

<Surface hydrophilicity evaluation>
The same HEMA gel or silicone hydrogel as the gel used for the evaluation of the surface friction coefficient is washed with 100 ml of ISO physiological saline, then immersed in another 100 ml of ISO physiological saline, the gel is pulled up, and the water film on the surface is cut. The time until was measured. Evaluation was performed according to the following criteria.
○: Time until the water film on the gel surface is cut off is 30 seconds or longer, Δ: Time until the water film on the gel surface is cut off is 10 seconds or more and less than 30 seconds, X: Time until the water film on the gel surface is cut off Less than 10 seconds.

<Acant amoeba adhesion prevention evaluation>
Lens sample preparation The product name “Seed 1day Fine UV” (manufactured by SEED) is thoroughly washed with ISO physiological saline, and then in the obtained care preparation or packaging solution (hereinafter sometimes referred to as polymer solution). It was immersed and autoclaved at 121 ° C. for 15 minutes. The sample after cooling was used for the measurement.
Medium preparation The following reagents were mixed and autoclaved at 121 ° C to obtain a PYG liquid medium.
Proteosepeptone (Sigma Aldrich) 10 g, Yeast Extract (Becton Dickinson) 0.5 g, 0.05 M CaCl ₂ 4 ml, 0.4 M MgSO ₄ .7H ₂ O 5 ml, 0.25 M Na ₂ HPO ₄ · 7H ₂ O 5 ml, 0.25M KH ₂ PO ₄ 5 ml, 0.005M Fe (NH ₄ ) ₂ (SO ₄ ) ₂ · 6H ₂ O 5 ml, 2M glucose solution 25 ml, ion-exchanged water 450 ml.
Measurement method Acanthamoeba was added to a culture flask containing PYG liquid medium and cultured at 25 ° C. for 3 to 4 days. The cultured Acanthamoeba was scraped off from the bottom of the flask with a cell scraper, and the medium was removed with a centrifuge (2000 rpm). Next, a phosphate buffer solution was added to adjust to about 1 × 10 ⁷ cells / ml to obtain an amoeba suspension.

2 ml of amoeba suspension and one lens were placed in a PP tube and cultured for 10 minutes at 37 ° C. with shaking (150 rpm). At this time, two types of lenses shown in the following conditions 1 and 2 were used.
Condition 1: A lens after autoclave sterilization was taken out of the polymer solution immediately before the evaluation, and a lens washed with ISO physiological saline was used.
Condition 2: The lens after autoclave sterilization was taken out, washed with ISO physiological saline, and allowed to stand in ISO physiological saline for about 12 hours.
The cultured lens was taken out, excess amoeba was removed from the lens with phosphate buffer, and finally the lens was transferred to a 24-well plate containing 500 μl phosphate buffer. Add 500 μl of ATP extraction reagent (trade name “Lucifer 250 Plus”, manufactured by Kikkoman Co., Ltd.) to the well containing the lens, and stir the solution. 50 μl of “plus” (manufactured by Kikkoman) was added and stirred. The amount of luminescence was measured after 20 seconds, and the amoeba adhesion inhibitory effect was determined from the amount of luminescence based on the following criteria.
In a solution to which a polymer described later is not added, the care product was based on Comparative Example 1-1 and the packaging solution was based on Comparative Example 2-1.
Judgment: ○: The amount of luminescence is less than 30, Δ: The amount of luminescence is 30 or more and less than 50, ×: The amount of luminescence is 50 or more.

Synthesis Example 1-1 (Polymer A-1; MPC0.50-SMA0.05-NIPA0.45)
MPC (manufactured by NOF Corporation) 30.82 g, stearyl methacrylate (SMA, manufactured by NOF Corporation) 3.54 g, N-isopropylacrylamide (NIPA, manufactured by Tokyo Chemical Industry Co., Ltd.) 10.64 g were added to 55.0 g of ethanol. Dissolved and placed in a 4-neck flask and blown with nitrogen for 30 minutes. Thereafter, 0.10 g of a trade name “Perbutyl ND” (manufactured by NOF Corporation) (hereinafter abbreviated as PB-ND) was added at 50 ° C., and a polymerization reaction was performed for 8 hours. The polymerization solution was added dropwise with stirring in 3 liters of diethyl ether, and the deposited precipitate was filtered and vacuum dried at room temperature for 48 hours to obtain 41.3 g of powder. The molecular weight evaluated by GPC was a weight average molecular weight of 1,000,000. This is designated as Polymer A-1. The data of IR, NMR and elemental analysis are shown below.

IR ^{data: 2966cm -1 (-CH), 1735cm} -1 (O-C = O), 1659cm -1 (N-C = O), 1460cm -1 (-CH), 1254cm -1 (P = O), 1169 cm ⁻¹ (C—O—C), 997 cm ⁻¹ (P—O—C).
NMR _{Data: 0.8-1.2ppm (CH 3 -C -)} , 1.3ppm (-CH 2 -), 3.3ppm (-N (CH 3) 3), 3.9ppm (-N-CH) _{, 3.7-4.4ppm (-CH 2 CH 2 -} ).
Elemental analysis data:
Theoretical value: C; 54.95%, H; 8.73%, N; 7.95%,
Found: C; 54.93%, H; 8.73%, N; 7.96%.
From the above results, it was found that the chemical structure of the obtained polymer A-1 was a polymer copolymerized at a ratio of MPC of 50 mol%, SMA of 5 mol%, and NIPA of 45 mol%. .

Synthesis Examples 1-2 to 1-9
Polymerization, purification, and desolvation were performed in the same manner as in Synthesis Example 1-1 except that the monomers, solvents, and polymerization initiators shown in Tables 1 and 2 were used. Polymer A-2 to Polymer A-9 Got. Tables 1 and 2 show the composition, molecular weight, and the like.
In the table, NTBA is N- (t-butyl) acrylamide, HEAA is N- (2-hydroxyethyl) acrylamide, LMA is lauryl methacrylate, VMA-70 is long-chain alkyl methacrylate (product) The name “Blemmer VMA-70”, manufactured by NOF Corporation, C16-C24 alkyl methacrylate mixture, alkyl group average chain length: 21) are shown respectively.

Synthesis Example 2-1 (Polymer B-1; MPC0.90-SMA0.02-NTBA0.08)
MPC 32.90 g, SMA 0.84 g, N- (t-butyl) acrylamide (NTBA, manufactured by Tokyo Chemical Industry Co., Ltd.) 0.1.26 g was dissolved in ethanol 55.0 g, placed in a 4-neck flask, and nitrogen was added for 30 minutes. Infused. Then, PB-ND0.10g was added at 50 degreeC, and it was made to superpose | polymerize for 8 hours. The polymerization solution was added dropwise while stirring in 3 liters of diethyl ether, and the deposited precipitate was filtered and vacuum dried at room temperature for 48 hours to obtain 31.6 g of powder. The molecular weight evaluated by GPC was a weight average molecular weight of 500,000. This is designated as Polymer B-1.

Synthesis Example 2-2 to Synthesis Example 2-6
Polymerization was carried out in the same manner as in Synthesis Example 2-1 except that each monomer, solvent, and polymerization initiator shown in Table 3 were used to obtain polymers B-2 to B-6. The composition, molecular weight, etc. are shown in Table 3.

Example 1-1
0.10 g of the polymer A-1 obtained in Synthesis Example 1-1, 0.50 g of 20% by weight polyhexanide chloride solution, 7.30 g of sodium chloride, 1.0 g of potassium chloride, 4.31 g of disodium hydrogen phosphate, 0.33 g of sodium dihydrogen phosphate and 987.06 g of purified water were charged into a pressure vessel and stirred at 80 ° C. for 1 hour. After cooling, it was filtered through cellulose acetate (0.2 μm) to obtain a contact lens care preparation S-1.

Example 1-2 to Example 1-11
Using the polymers A-1 to A-9 obtained in Synthesis Example 1-1 to Synthesis Example 1-9, contact lens care formulations S-2 to S-11 were prepared in the same manner as in Example 1-1. did. Tables 4 and 5 show the composition of each raw material.

Comparative Example 1-1
A contact lens care preparation T-1 was prepared in the same manner as in Example 1-1 except that the polymer was not used. The composition is shown in Table 6.

Comparative Example 1-2 to Comparative Example 1-10
Contact lens care preparations T-2 to T-10 were prepared in the same manner as in Example 1-1 with the compositions shown in Tables 6 and 7. In the table, HEC represents hydroxyethyl cellulose and PVP represents polyvinylpyrrolidone.

Evaluation of Care Preparations Prepared in Example 1-1 to Example 1-11 100 ml of the prepared care preparations S-1 to S-11 were collected, and HEMA gel or silicone hydrogel was immersed in the liquid overnight. . The surface friction coefficient and surface hydrophilicity of the immersed gel were measured and evaluated. The results are shown in Tables 8 and 9.
Moreover, 10 ml of care preparations S-1 to S-11 were collected, and the adhesion to Acanthamoeba was evaluated using a commercially available soft contact lens. The results are shown in Tables 10 and 11.
From the results of Tables 8 and 9, it can be seen that the lubricity of the gel surface was improved because the coefficient of friction was low as compared with the measurement result of care preparation T-1 not containing the polymer of Comparative Example 1-1. Moreover, it can be seen from the results of Tables 10 and 11 that the amount of the amoeba adhered was reduced.

Evaluation of Care Formulations Prepared in Comparative Example 1-1 to Comparative Example 1-10 100 ml of the prepared care formulations T-1 to T-10 were collected, and HEMA gel or silicone hydrogel was immersed in the liquid overnight. . The surface friction coefficient and surface hydrophilicity of the immersed gel were measured and evaluated. The results are shown in Tables 12 and 13.
Moreover, 10 ml of care preparations T-1 to T-10 were collected and evaluated for acanthamoeba adhesion using a commercially available soft contact lens. The results are shown in Tables 14 and 15.

Example 2-1
1 g of the polymer A-1 obtained in Synthesis Example 1-1 was collected, and dissolved in 499 g of ISO physiological saline at 80 ° C. for 1 hour. This solution was filtered through a cellulose acetate (0.2 μm) membrane filter to obtain a packaging solution U-1.

Example 2-2 to Example 2-9
Using the polymers A-2 to A-9 obtained in Synthesis Examples 1-2 to 1-9, packaging solutions U-2 to U-9 were obtained in the same procedure as in Example 2-1.

Evaluation of packaging solutions prepared in Example 2-1 to Example 2-9 The packaging solutions U-1 to U-9 prepared in Example 2-1 to Example 2-9 were respectively applied to 110 cc screw tubes. 100 ml was taken and HEMA gel or silicone hydrogel was immersed in it. The surface friction coefficient and surface hydrophilicity of the gel after immersion were evaluated. The results are shown in Tables 16 and 17.
Moreover, 10 ml of packaging solutions U-1 to U-9 were collected, and the trade name “Seed 1day Fine” (manufactured by SEED), which is a commercially available soft contact lens washed with sterilized ISO physiological saline in this solution. One sheet was immersed. After immersion, autoclave sterilization was performed at 121 ° C. Acanthamoeba adhesion was evaluated for soft contact lenses treated with packaging solutions U-1 to U-9. The results are shown in Tables 18 and 19.
From Tables 16 and 17, it was found that in the packaging solutions U-1 to U-9, the friction coefficient was greatly reduced as compared with the case where no polymer was used (Comparative Example 2-1). Moreover, from Tables 18 and 19, it was found that the amount of amoeba adhered was reduced as compared with Comparative Example 2-1, which was evaluated with ISO physiological saline.

Comparative Example 2-1
ISO physiological saline was used as the packaging solution without the polymer. This is designated as packaging solution V-1.

Comparative Example 2-2 to Comparative Example 2-7
Using the polymers B-1 to B-6 obtained in Synthesis Example 2-1 to Synthesis Example 2-6 and dissolving in ISO physiological saline in the same manner as in Example 2-1, packaging solution V -2 to V-6 were prepared.

Evaluation of Packaging Solution Prepared in Comparative Example 2-1 to Comparative Example 2-7 In the same manner as in Example 2-1 to Example 2-9, HEMA gel or Silicone hydrogel was immersed. The surface friction coefficient and surface hydrophilicity of the gel after immersion were evaluated. The results are shown in Table 20.
Moreover, the process similar to Example 2-1 to Example 2-9 was performed, and the acanthamoeba adhesion prevention ability was evaluated. The results are shown in Table 21.

Claims (2)

For contact lenses comprising a solution containing 0.01 to 2.0% by weight / volume% of a polymer having a weight average molecular weight of 5,000 to 2,000,000 having structural units represented by formulas (1a) to (1c) Care formulation.

(In the formula, R ¹ , R ² and R ⁴ each independently represent a hydrogen atom or a methyl group. R ³ represents an isopropyl group, a t-butyl group or a 2-hydroxyethyl group. R ⁵ represents 12 to 12 carbon atoms. 24 represents a monovalent hydrocarbon group, n1, n2, and n3 represent the molar ratio of structural units, and satisfy n1: n2: n3 = 100: 10 to 400: 2 to 50)   A contact lens packaging solution comprising the contact lens care preparation according to claim 1.