JP2017151437A - Solution for soft contact lenses - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solution for soft contact lenses which can prevent the deposition of protein onto a soft contact lens by imparting protein deposition inhibitory effect to the soft contact lens.SOLUTION: The present invention provides a solution for soft contact lenses comprising a copolymer (P) having three different constitutional units at a specific ratio, and a boric acid buffer agent (Q).SELECTED DRAWING: None

Description

The present invention relates to a solution for a soft contact lens containing a copolymer and a borate buffer, and more specifically, imparts a good wearing feeling by being able to suppress the adhesion of protein to the soft contact lens, and further provides a soft contact. The present invention relates to a soft contact lens solution, a soft contact lens shipping solution, and a soft contact lens care product that are excellent in safety by suppressing lens deformation.
This application claims the priority of Japanese Patent Application No. 2006-031568, which is incorporated herein by reference.

In recent years, it has been said that there are over 10 million soft contact lens wearers in Japan, and it has become a widely used medical device in Japan. In addition, due to its simplicity and convenience, the wearing time of soft contact lenses is increasing, and there is a report that the average wearing time per day among young soft contact lens wearers is about 14 hours ( Non-patent document 1). As the average wearing time per day becomes longer, the good wearing feeling of soft contact lenses is often lost, and there is still a demand for soft contact lenses that maintain good wearing feeling from the market. It is.
In the first place, the eyes are covered with tear fluid, and the surface of the soft contact lens is covered with tear fluid while the soft contact lens is worn. In addition to water, tear fluid components are known to contain electrolytes such as sodium ions and potassium ions, and proteins such as lysozyme and albumin (Non-patent Document 2).

Furthermore, when the soft contact lens is worn for about 14 hours per day, protein derived from tear fluid adheres to the surface of the soft contact lens, and protein contamination occurs. And it has also been reported that the feeling of wearing may be poor due to protein stains adhering to the surface of the soft contact lens (Non-patent Document 3).
A copolymer using 2- (methacryloyloxy) ethyl-2 ′-(trimethylammonio) ethyl phosphate (also known as 2-methacryloyloxyethyl phosphorylcholine, hereinafter sometimes abbreviated as MPC) (patent) Although it is known that the use of Document 1 and Patent Document 2) is excellent in the protein adhesion suppressing effect and wearing feeling, the protein adhesion suppressing effect and wearing feeling are not sufficient. Furthermore, since the copolymer has an insufficient protein adhesion inhibitory effect, the wearing feeling of the soft contact lens is not necessarily sufficient.

  Moreover, in order to improve a feeling of wearing, the method of improving the lubricity of a soft contact lens is known (patent document 3). On the other hand, the present situation is that nothing is known about the effect, use, and method of suppressing protein adhesion to the soft contact lens using the polymer described in Patent Document 3.

International Publication No. 99/026637 US Pat. No. 5,461,433 International Publication No. 2013/128633

Walline J. J., 2013, Long-term Contact Lens Wear of Children and Teens, Eye & Contact Lnes, 39, 283-289. Tiffany J. M., 2003, Tears in Health and Disease, Eye, 17, 923-926. Subbaraman L. N., et al., 2012, Protein Deposition and Clinical Symptoms in Daily Wear of etafilcon Lenses, Optom. Vis. Sci., 89, 1450-1459.

  The conventional soft contact lens cannot maintain a good wearing feeling. The present inventors have conceived that, if protein adhesion to a soft contact lens can be suppressed, a soft contact lens that maintains a better wearing feeling can be obtained.

  Then, the subject of this invention is providing the solution for soft contact lenses which can suppress adhesion of the protein to a soft contact lens by providing the protein adhesion suppression effect with respect to a soft contact lens.

As a result of intensive studies to solve the above problems, the inventors of the present invention have a specific proportion of a copolymer (P) having three different structural units in a specific proportion and a borate buffer (Q). The present inventors have found that the above-mentioned problems can be solved by the contained soft contact lens solution and have completed the present invention.
That is, the present invention includes the following [1] to [5].

[1] has a structural unit represented by the formula (1a) ~ formula (1c), the molar ratio _n a of the respective structural _units: n b: _{n c} is 100: 10 to 400: 2 to 50, weight Copolymer (P) having an average molecular weight of 5,000 to 2,000,000 0.01 to 2.0 w / v%, borate buffer (Q) 0.01 to 10.0 w / v%, A solution for soft contact lenses.

R ¹ , R ² and R ⁵ each independently represent a hydrogen atom or a methyl group, and R ³ and R ⁴ each independently represent a hydrogen atom, a methyl group, an ethyl group, or a morpholino group bonded to each other. Indicates. R ⁶ represents a monovalent hydrocarbon group having 12 to 24 carbon atoms.

  [2] The soft contact lens solution according to [1], further containing 0.01 to 1.5 w / v% sodium chloride and / or 0.01 to 1.5 w / v% potassium chloride.

  [3] The soft contact lens solution according to [1] or [2], which is applied to a soft contact lens classified into Group I or Group IV.

  [4] The soft contact lens solution according to any one of [1] to [3], which is a shipping solution for soft contact lenses.

  [5] The soft contact lens solution according to any one of [1] to [3], which is a care product for soft contact lenses.

  The solution for a soft contact lens of the present invention gives a good wearing feeling by being able to suppress the adhesion of proteins to the soft contact lens, and is excellent in safety by suppressing the deformation of the soft contact lens.

  The solution for soft contact lenses of the present invention contains a copolymer (P) and a borate buffer (Q).

<Copolymer (P)>
The copolymer (P) used for the soft contact lens solution of the present invention has three structural units represented by the following formulas (1a) to (1c), and the molar ratio (configuration ratio) of each structural unit. _{n a:} n b: n _c is 100: 10 to 400: 2 to 50.

<(1) PC constitutional unit>
The copolymer (P) used for the soft contact lens solution of the present invention has a structural unit represented by the following formula (1a) (hereinafter abbreviated as “PC structural unit”).

In the above formula (1a), R ¹ represents a hydrogen atom or a methyl group.
The PC structural unit in the copolymer (P) is introduced to the copolymer (P) in order to enhance the protein adhesion inhibiting effect.
The PC structural unit in the copolymer (P) is a phosphorylcholine-like group-containing monomer (hereinafter referred to as PC monomer) represented by the following formula (1a ′) used during the polymerization of the copolymer (P). Obtained from).

  In the formula (1a ′), X represents a monovalent organic group having a polymerizable functional group having an unsaturated bond. As the PC monomer, for example, 2-((meth) acryloyloxy) ethyl-2 ′-(trimethylammonio) ethyl phosphate is preferable from the viewpoint of availability, and is further represented by the following formula (1a ″). 2- (Methacryloyloxy) ethyl-2 ′-(trimethylammonio) ethyl phosphate is preferred.

  The PC monomer can be produced by a known method. For example, a method of reacting a compound obtained by reacting a hydroxyl group-containing monomer and 2-bromoethyl phosphoryl dichloride in the presence of a tertiary base with a tertiary amine as disclosed in JP-A-54-63025, And a ring-opening reaction with a tertiary amine after obtaining a cyclic compound by the reaction of a hydroxyl group-containing polymerizable monomer and a cyclic phosphorus compound, as described in JP-A-58-154591. .

<(2) Amide structural unit>
The copolymer (P) used in the soft contact lens solution of the present invention has a structural unit represented by the following formula (1b) (hereinafter abbreviated as “amide structural unit”).

In the formula (1b), R ² represents a hydrogen atom or a methyl group, and R ³ and R ⁴ each independently represent a hydrogen atom, a methyl group, an ethyl group, or a morpholino group bonded to each other.
The amide structural unit in the copolymer (P) is introduced in order to increase the molecular weight of the copolymer (P) and to improve the adhesion to the soft contact lens.

The proportion of the copolymer (P) amide structural units within, for the number of moles _{n b} when the number of moles _{n a} of PC constituent units is _100, a n _b / n a = 10 to 400/100, Preferably it is 30-250 / 100. If _nb is too large, it may be difficult to perform aseptic filtration required when producing a solution for soft contact lenses. If it is too small, adhesion to the soft contact lenses will not be improved, and protein adhesion will occur. The suppression effect cannot be expected.

  The amide structural unit in the copolymer (P) is a monomer represented by the following formula (1b ′) used during the polymerization of the copolymer (P), that is, a (meth) acrylamide or a (meth) acrylamide derivative. Obtained from.

Each ^R 2, ^{R 3} and ^{R 4} in the formula (1b ') is the same as ^R 2, ^{R 3} and ^{R 4} in the formula (1b).
Examples of the (meth) acrylamide or (meth) acrylamide derivative represented by the above formula (1b ′) include N, N-dimethyl (meth) acrylamide, N, N-diethyl (meth) acrylamide or N-acryloylmorpholine. It is done.

<(3) Hydrophobic structural unit>
The copolymer (P) used in the soft contact lens solution of the present invention has a structural unit represented by the following formula (1c) (hereinafter abbreviated as “hydrophobic structural unit”).

In the above formula (1c), R ⁵ represents a hydrogen atom or a methyl group, and R ⁶ represents a monovalent hydrocarbon group having 12 to 24, 12 to 22 or 12 to 18 carbon atoms. Specifically, R ⁶ is, for example, a lauryl group, a stearyl group, or a behenyl group.
The hydrophobic structural unit in the copolymer (P) is introduced in order to enhance the adsorptivity to the soft contact lens and to impart a protein adhesion inhibiting effect to the soft contact lens.

The proportion of the hydrophobic structural unit in the copolymer (P), the number of moles _{n c} when the number of moles _{n a} of PC configuration units as _100, be a n _c / n a = 2 to 50/100 , Preferably 5 to 25/100. If n _c is too small, not enough protein adhesion inhibiting effect, if too large decreases the solubility in aqueous solution by lowering the hydrophilicity of the copolymer (P), a solution for soft contact lenses May be difficult to manufacture.
The hydrophobic structural unit in the copolymer (P) is obtained from a hydrophobic monomer represented by the following formula (1c ′) used during the polymerization of the copolymer (P).

^{R 5} and ^{R 6} in Formula (1c '), the same as ^{R 5} and ^{R 6} in the formula (1c).
Examples of the hydrophobic monomer represented by the formula (1c ′) include linear alkyl (meth) acrylates such as lauryl (meth) acrylate, stearyl (meth) acrylate, and behenyl (meth) acrylate.

<Other structural units>
The copolymer (P) used for this invention can also introduce | transduce structural units other than the structural unit represented by Formula (1a)-Formula (1c) in the range which does not impair the effect of this invention. When the following other polymerizable monomer is blended with the monomer composition used for the synthesis of the copolymer (P), the blending ratio can be appropriately selected within a range that does not affect the effects of the present invention. but is 100 to _{n a} shown by the formula (1a) constituting the copolymer (P), preferably 50 or less in molar ratio.

  Examples of other polymerizable monomers that can be used for the synthesis of the copolymer (P) include linear or branched alkyl (meth) acrylates, cyclic alkyl (meth) acrylates, and aromatic group-containing (meth). Acrylate, styrene monomer, vinyl ether monomer, vinyl ester monomer, hydrophilic hydroxyl group-containing (meth) acrylate, acid group-containing monomer, nitrogen-containing group-containing monomer, amino group-containing monomer And cationic group-containing monomers.

Examples of the linear or branched alkyl (meth) acrylate include methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, and the like.
Examples of the cyclic alkyl (meth) acrylate include cyclohexyl (meth) acrylate.
Examples of the aromatic group-containing (meth) acrylate include benzyl (meth) acrylate and phenoxyethyl (meth) acrylate.
Examples of the styrene monomer include styrene, methyl styrene, chloromethyl styrene and the like.
Examples of the vinyl ether monomer include methyl vinyl ether and butyl vinyl ether.
Examples of the vinyl ester monomer include vinyl acetate and vinyl propionate.

Examples of hydrophilic hydroxyl group-containing (meth) acrylates include polyethylene glycol (meth) acrylate, polypropylene glycol (meth) acrylate, 2-hydroxyethyl (meth) acrylate, 2-hydroxybutyl (meth) acrylate, and 4-hydroxybutyl. (Meth) acrylate etc. are mentioned.
Examples of the acid group-containing monomer include (meth) acrylic acid, (styrene) sulfonic acid (meth) acryloyloxyphosphonic acid, and the like.
Examples of the nitrogen-containing group-containing monomer include N-vinylpyrrolidone and the like.

Examples of the amino group-containing monomer include aminoethyl (meth) acrylate, dimethylamino (meth) acrylate, N, N-dimethylaminopropyl (meth) acrylamide, and the like.
Examples of the cationic group-containing monomer include 2-hydroxy-3- (meth) acryloyloxypropyltrimethylammonium chloride.

<Molecular weight of copolymer (P)>
The copolymer (P) used in the present invention has a weight average molecular weight of 5,000 to 2,000,000, 10,000 to 1,500,000, 50,000 to 1,400,000, or 100,000 to 1. 300,000, preferably 100,000 to 1,500,000 polymers. If the weight average molecular weight is less than 5,000, the adsorption force of the copolymer to the surface of the soft contact lens is not sufficient, and thus there is a possibility that the protein adhesion inhibitory effect cannot be expected, and if it exceeds 2,000,000, Aseptic filtration required for producing a contact lens solution may be difficult.

<Synthesis Method of Copolymer (P)>
The copolymer (P) used in the present invention can be obtained by radical polymerization of a blend of the above monomers. The copolymer (P) is synthesized, for example, by subjecting the monomer composition to radical polymerization in the presence of a radical polymerization initiator in the presence of an inert gas such as nitrogen, carbon dioxide, argon or helium or in an atmosphere. can do. The radical polymerization method can be performed by a known method such as bulk polymerization, suspension polymerization, emulsion polymerization, or solution polymerization. The radical polymerization method is preferably solution polymerization from the viewpoint of purification and the like. The copolymer (P) can be purified by a known purification method such as a reprecipitation method, a dialysis method, or an ultrafiltration method.

Examples of radical polymerization initiators include azo radical polymerization initiators, organic peroxides, and peroxides.
Examples of the azo radical polymerization initiator include 2,2-azobis (2-diaminopropyl) dihydrochloride, 2,2-azobis (2- (5-methyl-2-imidazolin-2-yl) propane) 2 Hydrochloride, 4,4-azobis (4-cyanovaleric acid), 2,2-azobisisobutyramide dihydrate, 2,2-azobis (2,4-dimethylvaleronitrile), 2,2-azobis An example is isobutyronitrile (AIBN).

Examples of the organic peroxide include t-butylperoxyneodecanate, benzoyl peroxide, diisopropylperoxydicarbonate, t-butylperoxy-2-ethylhexanoate, t-butylperoxypivalate, t-butylperoxydiisobutene. Tylate, lauroyl peroxide, t-butylperoxydecanate, succinic peroxide (= succinyl peroxide) and the like can be mentioned.
Examples of the persulfate include ammonium persulfate, potassium persulfate, and sodium persulfate.

  These radical polymerization initiators can be used alone or in combination of two or more. The amount of the polymerization initiator used is usually 0.001 to 10 parts by weight, 0.02 to 1.0 parts by weight, 0.03 to 1.0 parts by weight, based on 100 parts by weight of the monomer composition. It is 0.04-1.0 mass part or 0.05-1.0 mass part, Preferably it is 0.01-5.0 mass part.

The synthesis of the copolymer (P) can be performed in the presence of a solvent. Any solvent may be used as long as it dissolves the monomer composition and does not react. For example, water, alcohol solvents, ketone solvents, ester solvents, linear or cyclic ether solvents, nitrogen-containing solvents. Mention may be made of system solvents. Preferably, water or alcohol or a mixed solvent thereof is used.
Examples of the alcohol solvent include methanol, ethanol, n-propanol, and isopropanol.
Examples of the ketone solvent include acetone, methyl ethyl ketone, and diethyl ketone.
Examples of ester solvents include ethyl acetate.
Examples of the linear or cyclic ether solvent include ethyl cellosolve and tetrahydrofuran.
Examples of the nitrogen-containing solvent include acetonitrile, nitromethane, N-methylpyrrolidone and the like.

  The copolymer (P) contained in the soft contact lens solution of the present invention is 0.01 to 2.0 w / v% in water, alcohol such as methanol, ethanol, n-propanol, isopropanol, or a mixed solution thereof. It can be obtained by dissolving so that. If the concentration of the copolymer (P) is less than 0.01 w / v%, the protein adhesion inhibiting effect is not sufficient, and if it exceeds 2.0 w / v%, it is difficult to perform aseptic filtration when producing a soft contact lens solution. There is a risk of becoming.

  By using the copolymer (P) in the soft contact lens solution, it is possible to suppress the adhesion of protein stains to the soft contact lens while wearing the soft contact lens and to give a good wearing feeling to the soft contact lens wearer. can do.

(Borate buffer (Q))
The borate buffer (Q) used in the soft contact lens solution of the present invention is particularly a buffer that contains boric acid (borate ions) in the solution by dissolving in the soft contact lens solution. Preferably, but not limited to, a buffer containing boric acid, a buffer containing borax, a buffer containing boric acid and borax, a buffer containing boric acid and sodium hydroxide, boric acid and hydrochloric acid A buffer containing boric acid and sodium bicarbonate, a buffer containing borax and sodium hydroxide, a buffer containing borax and hydrochloric acid, a buffer containing borax and sodium bicarbonate An agent etc. can be illustrated.
When the solution for soft contact lenses of the present invention contains a borate buffer (Q), the effect of suppressing protein adhesion to the soft contact lenses is improved, and the pH and osmotic pressure can be adjusted, and there is no irritation. , Give good wearing feeling. Furthermore, since the soft contact lens solution of the present invention contains a borate buffer (Q), the soft contact lens is not deformed, and therefore, it is excellent in safety.

The concentration of the boric acid buffer (Q) is defined as a w / v% concentration as boric acid (H ₃ BO ₃ ), and can be obtained by calculation from the amount of boric acid buffer (Q). For example, when 1 g of borax (Na ₂ [B ₄ O ₅ (OH) ₄ ] · 8H ₂ O) is blended to make a soft contact lens solution 100 mL, the concentration of the borate buffer (Q) is As boric acid,
1 (g / 100 mL) × 61.833 (formula amount of H ₃ BO ₃ ) ÷ 381.37 (formula amount of Na ₂ [B ₄ O ₅ (OH) ₄ ] · 8H ₂ O) = 0.162 (g / 100 mL) = 0.162 w / v%
It becomes.
The borate buffer (Q) used in the present invention is 0.01 w / v% to 10.0 w / v%, 0.01 w / v% to 5.0 w / v%, 0% with respect to the soft contact lens solution. .05 w / v% to 5.0 w / v%, 0.1 w / v% to 5.0 w / v%, 0.1 w / v% to 2.0 w / v%, or 0.1 w / v% to 1. 0 w / v%. If it is less than 0.01 w / v%, it may be difficult to adjust the pH and osmotic pressure of the soft contact lens solution, and even if it is blended at a concentration higher than 10.0 w / v%, the added amount Proper protein adhesion suppression effect cannot be obtained.

  According to FDA (US Food and Drug Administration), Group I is “non-ionic and soft water with less than 50% water content” and Group II is “non-ionic and 50% water content”. The above-mentioned “soft contact lenses”, Group III is “ionic and soft contact lenses with a moisture content of less than 50%”, and Group IV is “ionic and soft contact lenses with a moisture content of 50% or more” It is specified that it can be classified into four types.

The solution for soft contact lenses of the present invention is preferably applied to a group I or group IV soft contact lens from the viewpoint of further enhancing the protein adhesion suppressing effect.
Specific examples of soft contact lenses classified into Group I or Group IV include the following. (Numerical values in parentheses indicate the moisture content, followed by the main components constituting the soft contact lens.)

(Group I soft contact lenses)
lotrafilcon A (24%, N, N-dimethylacrylamide / trimethylsiloxysilane siloxane), lotrafilcon B (33%, N, N-dimethylacrylamide / trimethylsiloxysilane siloxane), senofilcon A (38%, monofunctional polydimethyl) Siloxane / N, N-dimethylacrylamide / 2-hydroxyethyl methacrylate), garyfilcon A (47%, monofunctional polydimethylsiloxane / N, N-dimethylacrylamide / 2-hydroxyethyl methacrylate), comfilcon A (48%, aquaform) (Trademark)), polymacon A (38%, 2-hydroxyethyl methacrylate), polyhema (38%, 2-hydroxyethyl methacrylate) polymacon (38%, 2- hydroxyethyl methacrylate), tefilcon A (38%, 2- hydroxyethyl methacrylate)

(Group IV soft contact lenses)
etafilcon A (58%, 2-hydroxyethyl methacrylate / methacrylic acid), ocuconcon B (52%, 2-hydroxyethyl methacrylate / polyvinylpyrrolidone / methacrylic acid), ocufilcon D (55%, 2-hydroxyethyl methacrylate / polyvinylpyrrolidone / methanic acid) Methacrylic acid), phemefilcon A (55%, 2-hydroxyethyl methacrylate / ethoxyethyl methacrylate / methacrylic acid), vifilcon A (55%, 2-hydroxyethyl methacrylate / polyvinylpyrrolidone / methacrylic acid), methafilcon A (55%, 2%) -Hydroxyethyl methacrylate / methacrylic acid), buficon A (55%, 2-hydroxyethyl methacrylate / dia) Seton acrylamide / methacrylic acid), perfilcon A (71%, 2-hydroxyethyl methacrylate / N-vinylpyrrolidone / methacrylic acid)

  Among these, from the viewpoint of the effect of suppressing protein adhesion to the soft contact lens, the group I soft contact lenses are lotrafilcon A, lotrafilcon B, senofilcon A, galilfilcon A, comfilcon A, polymacon A, polyhema, polymacon, polymacon, polymacon, polymacon Is preferably used.

Furthermore, the soft contact lens solution of the present invention can be used as a general contact lens solution in addition to the copolymer (P) and borate buffer (Q), vitamins, amino acids, Sugars, thickening agents, cooling agents, inorganic salts, organic acid salts, acids, bases, antioxidants, stabilizers, preservatives, and the like can be blended.
Although the compounding quantity of components other than these copolymer (P) and boric acid buffer (Q) is not specifically limited, 0.01-5.0 w / v% is preferable, 0.05-4.0 w / v% is more preferable, and 0.1 to 3.0 w / v% is more preferable.

Examples of vitamins include flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, sodium pantothenate, calcium pantothenate and the like.
Examples of amino acids include aspartic acid or a salt thereof, aminoethylsulfonic acid, and the like.
Examples of the saccharide include glucose, mannitol, sorbitol, xylitol, trehalose and the like.
Examples of the thickening agent include hydroxypropylmethylcellulose and hydroxyethylcellulose.
Examples of the refreshing agent include menthol and camphor.
Examples of inorganic salts include sodium chloride, potassium chloride, sodium hydrogen phosphate, anhydrous sodium dihydrogen phosphate, and the like.
Examples of the organic acid salt include sodium citrate.
Examples of the acid include phosphoric acid, citric acid, sulfuric acid, acetic acid and the like.
Examples of the base include potassium hydroxide, trishydroxymethylaminomethane, monoethanolamine and the like.
Examples of the antioxidant include tocopherol acetate and dibutylhydroxytoluene.
Examples of the stabilizer include sodium edetate and glycine.
Examples of the preservative include benzalkonium chloride, chlorhexidine gluconate, potassium sorbate, and polyhexanide hydrochloride.

Among these components, it is preferable to add sodium chloride or potassium chloride, which is an inorganic salt, in terms of further improving the protein adhesion inhibiting effect.
Although the compounding quantity of sodium chloride is not specifically limited, 0.01-1.5 w / v% is preferable, 0.1-1.3 w / v% is more preferable, 0.2-1.1 w / v% is further preferable.
Although the compounding quantity of potassium chloride is not specifically limited, 0.01-1.5 w / v% is preferable, 0.02-1.3 w / v% is more preferable, 0.05-1.1 w / v% is further preferable.
In order to further improve the protein adhesion inhibiting effect, it is preferable to use sodium chloride and potassium chloride in combination. The compounding ratio of sodium chloride and potassium chloride at the time of combined use is a weight ratio, preferably sodium chloride: potassium chloride = 1: 1 to 50: 1, more preferably 2: 1 to 40: 1, and 3: 1 to 30. : 1 is more preferred.

  Specific examples of the product form of the soft contact lens solution of the present invention include the following. Specifically, soft contact lens shipping liquid, soft contact lens care product, soft contact lens preserving liquid, soft contact lens cleaning liquid, soft contact lens cleaning preserving liquid, and the like. Especially, it is preferable to use for the shipping liquid for soft contact lenses, or the care goods for soft contact lenses. In the present specification, the soft contact lens shipping solution is a solution in which the soft contact lens is immersed when the soft contact lens product is shipped. In the present specification, the care product for soft contact lenses is not particularly limited as long as it is a solution used for the care of soft contact lens products. Liquid, disinfectant cleaning storage liquid, and mounting liquid.

The present invention has a structural unit represented by formula (1a) ~ formula (1c), the molar ratio _n a of the respective structural _units: n b: _{n c} is 100: 10 to 400: 2 to 50, The use of a copolymer (P) having a weight average molecular weight of 5,000 to 2,000,000 and a boric acid buffer (Q) for producing a soft contact lens solution is also an object. Here, the soft contact lens solution contains 0.01 to 2.0 w / v% of the copolymer (P) and 0.01 to 10.0 w / v% of the boric acid buffer (Q).
(R ¹ , R ² and R ⁵ each independently represent a hydrogen atom or a methyl group, and R ³ and R ⁴ each independently represent a hydrogen atom, a methyl group, an ethyl group or a morpholino bonded to each other. R ⁶ represents a monovalent hydrocarbon group having 12 to 24 carbon atoms.)

The present invention has a structural unit represented by formula (1a) ~ formula (1c), the molar ratio _n a of the respective structural _units: n b: _{n c} is 100: 10 to 400: 2 to 50, The use of a copolymer (P) having a weight average molecular weight of 5,000 to 2,000,000 and a borate buffer (Q) as a soft contact lens solution is also an object. Here, the solution for soft contact lenses contains 0.01 to 2.0 w / v% of the copolymer (P) and 0.01 to 10.0 w / v% of the boric acid buffer (Q). .
(R ¹ , R ² and R ⁵ each independently represent a hydrogen atom or a methyl group, and R ³ and R ⁴ each independently represent a hydrogen atom, a methyl group, an ethyl group or a morpholino bonded to each other. R ⁶ represents a monovalent hydrocarbon group having 12 to 24 carbon atoms.)

  Hereinafter, the present invention and its effects will be described in detail with reference to examples and comparative examples.

<Molecular weight measurement of copolymer>
5 mg of each copolymer obtained in Synthesis Examples 1 to 4 below was dissolved in a methanol / chloroform mixture (80:20) to obtain a sample solution. The following analysis conditions were used.
Column: PLgel-mixed-C
Standard substance: Polyethylene glycol Detector: Differential refractometer RI-8020 (manufactured by Tosoh Corporation)
Calculation method of weight average molecular weight: Molecular weight calculation program (GCP program for SC-8020)
Flow rate: 1 mL per minute
Injection volume: 100 μL
Column oven: constant temperature around 40 ° C

The weight average molecular weight of the copolymer shown in Table 1 below is a value of a weight average molecular weight measured by gel permeation chromatography (GPC) using polyethylene glycol as a standard sample.
The obtained copolymer solution was diluted with water so that it might become 0.5 mass%, and this liquid was filtered with a 0.45 micrometer membrane filter and measured.

<Synthesis of copolymer (P)>
[Synthesis Example 1]
8. MPC (manufactured by NOF Corporation) 31.8 g, stearyl methacrylate (SMA, manufactured by NOF Corporation) 3.6 g and N, N-dimethylacrylamide (DMAA, manufactured by Kojin Film & Chemicals Co., Ltd.) 6 g was put into a four-necked flask, dissolved with 55.0 g of ethanol, and nitrogen gas was blown in for 30 minutes. Thereafter, 0.10 g of a polymerization initiator (perbutyl (Japan registered trademark) ND (PB-ND), manufactured by NOF Corporation) which is t-butylperoxyneodecanate) was added, and a polymerization reaction was performed for 8 hours. After the polymerization reaction, the polymerization solution was added dropwise to 3 liters of diethyl ether while stirring, the deposited precipitate was filtered, and vacuum dried at room temperature for 48 hours to obtain a powder. The yield was 40.2g. This is designated as Copolymer 1. The weight average molecular weight based on GPC measurement of the copolymer 1 is 1,000,000, and the molar ratio of the copolymer components is MPC 100 mol%, DMAA 90 mol%, and SMA 10 mol%.

[Synthesis Examples 2 to 4]
Copolymers 2 to 4 were respectively synthesized according to the same procedure as in Synthesis Example 1 except that the types and amounts of components shown in Table 1 below were used. In addition, Table 1 shows the molar ratio, yield, and weight average molecular weight of the copolymer components.

<Polymer not (P)>
The polymer (polymer which is not (P)) used for the comparative example is as follows.
Homopolymer (A): 2-methacryloyloxyethyl phosphorylcholine polymer [weight average molecular weight: 200,000], which was obtained by polymerization according to the method described in Examples of JP-A-8-333421.
Homopolymer (B): a polymer of dimethylacrylamide [number average molecular weight: 10,000], purchased from Sigma Aldrich Japan (product name: Poly (N, N-dimethylcycloamide), DDMAT Terminated) and used for the test. .
Homopolymer (C): a polymer of lauryl methacrylate [weight average molecular weight: 470,000], purchased from Sigma-Aldrich Japan (product name: polylauryl methacrylate) and used for the test.

<Evaluation for suppressing protein adhesion to soft contact lenses 1>
"Protein adhesion inhibition evaluation 1 to soft contact lens" was tested according to the following procedure with reference to the following literature 1. In conducting the test, “protein soil solution”, “protein soil extract” and “ISO physiological saline solution” were prepared in advance and “pretreatment of soft contact lens” was performed.

"Preparation of protein soil solution"
A protein soil solution was prepared with reference to Reference 2 and Reference 3 below.
Sodium chloride 1.8 g, sodium dihydrogen phosphate dodecahydrate 0.1516 g, sodium dihydrogen phosphate dihydrate 0.0368 g, calcium chloride hydrate 0.0816 g, lysozyme (derived from egg white) 24 g and albumin (derived from bovine serum) 0.776 g were weighed and dissolved in water to make 200 mL to obtain a protein soil solution.

"Preparation of protein soil extract"
Trifluoroacetic acid: purified water: acetonitrile was mixed at a ratio of 0.6 g: 300 mL: 300 mL to obtain a protein soil extract.

"Preparation of ISO physiological saline"
An ISO physiological saline solution was prepared with reference to Reference 4 below.
8.3 g of sodium chloride, 5.993 g of sodium hydrogen phosphate dodecahydrate, 0.528 g of sodium dihydrogen phosphate dihydrate were weighed, dissolved in water to 1000 mL, and filtered to obtain an ISO physiological saline solution .

"Pretreatment of soft contact lenses"
(1) 10 mL or more of ISO physiological saline was put into a 15 mL centrifuge tube, and one soft contact lens (etafilcon A, group IV) was taken out from the blister pack, put into the 15 mL centrifuge tube, and shaken for 2 hours.
(2) The ISO physiological saline solution in the centrifuge tube was removed, and 10 mL or more of the ISO physiological saline solution was added again and shaken overnight.
(3) The soft contact lens was taken out from the 15 mL centrifuge tube, the water was gently wiped off, and the contact lens was placed in a soft contact lens case. 1 mL of the contact lens shipping solution of each example or each comparative example was added thereto, and autoclaving (121 ° C., 20 minutes) was performed for protein adhesion inhibition evaluation.

"Method for evaluating protein adhesion inhibition to soft contact lenses"
(1) 2 mL of protein soil solution was put into a 10 cc sample tube bottle, and one soft contact lens pretreated with the shipping solution for contact lenses of each Example or each Comparative Example was placed one by one and immersed at 37 ° C. for 4 hours.
(2) After this treatment, the soft contact lens was removed from the sample tube bottle and rinsed with water.
(3) The water adhering to the soft contact lens was removed, 4 mL of the protein soil extract was placed in a separately prepared sample tube bottle, and the soft contact lens was immersed for 16 hours or more to extract the protein soil.
(4) The protein soil extract after protein soil extraction was taken in a 100 μL test tube and further diluted 10-fold with the protein soil extract to a total of 1000 μL.
(5) About this liquid, the quantity of the protein stain | pollution | contamination adhering to a soft contact lens was quantified using MicroBCA Protein Assay Kit (Thermo Fisher Scientific).
(6) From the amount of protein stains adhering to the soft contact lens, the “protein adhesion inhibition rate (%)” was calculated using the following formula.

“Protein adhesion inhibition rate (%)” = {1− (amount of protein stain adhering to the soft contact lens when using each example or each comparative example) / (purified water (comparison control in Table 3)) Amount of protein stains attached to the soft contact lens when used)} × 100

Reference 1: Keith D., Hong B. and Christensen M .: A Novel Procedure for the Extraction of Protein Deposits from Soft Hydrophilic Contact Lenses for Analysis. Curr. Eye Res. 16: 503-510, 1997.
Reference 2: Hu J., Tartaglia L., Kohler J., Lett J., et al .: Gentle TouchTM, A Lens Material Resistant to Protein Deposition. CLAO J 21: 93-95, 1995.
Reference 3: Department of Health and Human Services, Food and Drug Administration: Testing Guidelines for Class III Soft (Hydrophilic) Contact Lens Solutions, Draft, 1985; Appendix B, p.30.
Reference 4: ISO 18369-3: 2006, Ophthalmic Optics-Contact Lenses Part3: Measurement Methods

<Deformation evaluation of soft contact lens>
The deformability of the soft contact lens was tested according to the following procedure.
(1) A total of two soft contact lenses (etafilcon A, group IV) were placed in each contact lens case.
(2) 1 mL of physiological saline was added to the left soft contact lens to serve as a negative control.
(3) In the right soft contact lens, 1 mL of the shipping solution for soft contact lens prepared in each example or each comparative example was added to prepare an evaluation sample.
(4) After adding a physiological saline solution or a contact lens shipping solution, the solution was allowed to stand at room temperature for 24 hours.
(5) After 24 hours of standing, the deformability of the negative control and the soft contact lens of the evaluation sample was visually confirmed.

<Preparation of shipping solution for soft contact lens>
[Example 1]
About 80 g of purified water was weighed, and copolymer 1 (0.01 g), 0.4 g of boric acid and 0.0072 g of sodium hydroxide were added thereto, stirred and dissolved. Thereafter, purified water was added thereto so that the total amount was 100 mL. Thereafter, filtration sterilization was performed to obtain a sterile contact lens shipping solution. The appearance and properties of this contact lens shipping liquid are shown in Table 2 below.

[Examples 2 to 6]
A sterile contact lens shipping solution was prepared according to the same procedure as in Example 1 except that the types and amounts of components shown in Table 2 were used. The appearance and properties of each example are shown in Table 2 below.

[Comparative Examples 1 to 5, Comparative Control]
A sterile contact lens shipping solution was prepared according to the same procedure as in Example 1 except that the types and amounts of components shown in Table 3 were used. The appearance and properties of each comparative example are shown in Table 3 below.

For each example and each comparative example, the protein adhesion inhibition evaluation 1 to the soft contact lens was performed, and the protein adhesion inhibition rate was calculated. The protein adhesion inhibition rate (%) of each Example and each Comparative Example is shown in Table 2 and Table 3 above, respectively.
In Comparative Example 3, since it was insoluble in water, protein adhesion suppression evaluation could not be performed. In Comparative Example 1, Comparative Example 2 and Comparative Example 5, the results were 1.3%, 0.1% and 3.1%, respectively, and almost no protein adhesion suppressing effect was shown.
On the other hand, in Example 1- Example 6, the protein adhesion inhibitory effect of 6.3% -28.1% was shown. From Example 1 to Example 3, it was found that the protein adhesion suppressing effect was also improved according to the blending concentration of the copolymer (P). Furthermore, from Example 4 to Example 6, it was found that Copolymer 2 to Copolymer 4 also showed a protein adhesion inhibitory effect in the same manner as Copolymer 1.

Furthermore, the presence or absence of deformability of the contact lens was also evaluated. The presence or absence of deformability of the contact lenses of each Example and each Comparative Example is shown in Tables 2 and 3 above.
In Examples 1 to 6, there was no deformation of the contact lens. In Comparative Example 4, although the protein adhesion inhibitory effect was expressed because the copolymer 1 was blended, since the boric acid buffer (Q) was not included, the contact lens was deformed. It was shown that it can not be used as.

<Protein adhesion inhibition evaluation 2 for soft contact lenses>
The soft contact lens classified as group IV (etafilcon A, group IV) used in the above-described evaluation 1 for inhibiting protein adhesion to the soft contact lens is changed into a soft contact lens classified as group I (senofilcon A, group I). A protein adhesion suppression evaluation to the soft contact lens was performed by the same method except that it was changed.
In addition, the shipping solution for soft contact lenses of Examples 1 to 3 was used for protein adhesion suppression evaluation. The evaluation results are shown in Table 4 below.

The protein adhesion suppression evaluation result in the soft contact lens (senofilcon A) classified into Group I using the shipping solution for soft contact lens of Example 1 to Example 3 is 85.3 to 95.1%, and the group It showed a remarkable protein adhesion inhibitory effect over soft contact lenses classified as IV.
From the above results, when the soft contact lens solution of the present invention is applied to a group IV soft contact lens, it suppresses the binding caused by hydration, which is a factor that causes protein to adhere to the soft contact lens, and the effect is exhibited. Conceivable. Furthermore, when applied to a group I soft contact lens, since the group I soft contact lens itself is non-ionic, it suppresses not only bonds resulting from hydration but also bonds resulting from ionicity. It is considered that adhesion suppression has been realized.

  Furthermore, for the purpose of further improving the protein adhesion suppressing effect, Examples 7 to 11 shown below were manufactured and evaluated.

[Examples 7 to 11]
A sterile contact lens shipping solution was prepared according to the same procedure as in Example 1 except that the types and amounts of components shown in Table 5 were used. The appearance and properties of each example are shown in Table 5 below.

  In the same manner as in the previous examples and comparative examples, the protein adhesion inhibition evaluation 1 to the soft contact lens was performed for Examples 7 to 11, and the protein adhesion inhibition rate was calculated. Table 5 shows the protein adhesion inhibition rate (%) of Examples 7 to 11. In Example 7 to Example 11, the protein adhesion suppressing effect of 8.7 to 30.2% was shown.

Next, the presence or absence of deformability of the contact lens was also evaluated. Table 5 shows the presence or absence of deformability of the contact lenses of Examples 7 to 11.
In Examples 7 to 11, no deformation of the contact lens was observed.

  Furthermore, about Example 7-Example 11, the protein adhesion suppression evaluation 2 to a soft contact lens was implemented. The evaluation results are shown in Table 6.

  The protein adhesion suppression evaluation 2 in the soft contact lens classified into group I using the shipping solution for soft contact lens of Examples 7 to 11 is 88.1 to 97.4%, and is classified into Group IV. It showed a remarkable protein adhesion inhibitory effect over soft contact lenses.

  From the above results, the protein adhesion inhibitory effect is improved by adding inorganic salts such as sodium chloride and / or potassium chloride in addition to the copolymer (P) and borate buffer (Q) of the present invention. It has been shown.

  The solution for soft contact lenses of the present invention can easily impart protein stain adhesion to the soft contact lenses, so that it can give a good wearing feeling and further suppress the deformation of the soft contact lenses. It is also excellent in safety.

Claims (5)

Has a structural unit represented by the formula (1a) ~ formula (1c), the molar ratio _n a of the respective structural _units: n b: _{n c} is 100: 10 to 400: 2 to 50, weight average molecular weight Copolymer (P) 0.01-2.0 w / v%, which is 5,000-2,000,000, and borate buffer (Q) 0.01-10.0 w / v% Solution for soft contact lenses.
(R ¹ , R ² and R ⁵ each independently represent a hydrogen atom or a methyl group, and R ³ and R ⁴ each independently represent a hydrogen atom, a methyl group, an ethyl group or a morpholino bonded to each other. R ⁶ represents a monovalent hydrocarbon group having 12 to 24 carbon atoms.)   The solution for soft contact lenses according to claim 1, further comprising 0.01 to 1.5 w / v% sodium chloride and / or 0.01 to 1.5 w / v% potassium chloride.   The solution for soft contact lenses according to claim 1 or 2, which is applied to soft contact lenses classified into Group I or Group IV.   The solution for soft contact lenses according to claim 1, which is a shipping solution for soft contact lenses.   The solution for soft contact lenses according to claim 1, which is a care product for soft contact lenses.