JP2000109892A - Polysaccharide-containing liquid agent for contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a liquid agent which combines a high detergent effect and safety, by blending a protease and/or a lipase with chondroitin sulfate and/or hyaluronic acid or a salt thereof. SOLUTION: The protease and the lipase are each blended usually in an amount of 0.001-10 wt.%. The content of chondroitin sulfate and/or hyaluronic acid or a salt thereof is preferably 0.001-10 wt.%. Chondroitin sulfate and/or hyaluronic acid preferably has a molecular weight of five millions or less. This liquid agent may further contain a fungicide, a surface active agent, a polyol and the like. The fungicide is preferably a polyhexamethylene biguanide, a salt thereof or α-4-[1-tris(2-hydroxyethyl)ammonium chloride-2-butenyl]poly[1- dimethyl-ammonium chloride-2-butenyl]-ω-tris(2-hydroxyethyl)ammonium chloride.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid preparation having excellent detergency for contact lenses, especially soft contact lenses and oxygen-permeable hard contact lenses.

[0002]

2. Description of the Related Art A contact lens is a medical device to be directly inserted into an eye, but the wearing of the contact lens inevitably causes attachment of soils derived from a living body such as proteins, lipids and inorganic salts. In addition, since contact lenses are handled with fingers, cosmetics,
Contaminants from outside the body, such as hand creams and hair sprays, often adhere. If these stains are left unchecked, the permeability of the lens will be reduced and it will be difficult to see, and not only will the feeling of wearing deteriorate, but also the oxygen permeability will decrease, shortening the life of the contact lens and further reducing the risk of infection. May have an adverse effect on Contact lenses are roughly classified into hard contact lenses and soft contact lenses, and hard contact lenses with good oxygen permeability and water-containing soft contact lenses, which have been developed in recent years with the aim of better wearing feeling, are particularly Since dirt easily adheres, it is important to remove contaminants in order to take advantage of its excellent properties. There is a method using a protease or a lipolytic enzyme to remove attached protein or fat stains, and care products such as cleaning solutions containing these enzymes have already been put into practical use. Usually, in order to wash a contact lens with such an enzyme-containing solution, a method of rubbing in a solution or appropriately diluting an enzyme solution and immersing it in a diluting solution is adopted.

[0003]

However, in the case of an enzyme-containing solution for scrubbing, it is important to stably store an unstable enzyme in water, and not only a sufficient detergency cannot be obtained but also an enzyme. There is a fear that the washing effect of the stencil is reduced. Therefore, in order to supplement the sufficient cleaning effect, the use of a strong surfactant and physical cleaning with an abrasive may be added in some cases, but this is not always preferable in terms of safety. On the other hand, in the case of the enzyme-containing liquid for immersion cleaning, the cleaning effect is not sufficient for the dirt which has adhered, and the cleaning effect varies because the dilution ratio is not accurate.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies for the purpose of providing an enzyme-containing solution for a contact lens which has a high cleaning effect and is safe. The present inventors have found that a solution for contact lenses having a high cleaning effect and safety suitable for the above purpose can be obtained by incorporating a degrading enzyme and a certain polysaccharide together, and completed the present invention. That is, the present invention provides a contact lens solution containing a protease and / or a lipolytic enzyme and chondroitin sulfate and / or hyaluronic acid or a salt thereof.

[0005] Polysaccharides such as chondroitin sulfate and hyaluronic acid are also components in tears, and disinfectants for contact lenses and preservatives for contact lenses containing these are known (JP-A-63-59960, JP-A-Hei-8). −2534
19). However, Japanese Patent Application Laid-Open No. 63-59960 only describes that sodium chondroitin sulfate prevents the disinfectant component from adsorbing to the contact lens and suppresses the change in the physical properties of the contact lens. Japanese Utility Model Application Laid-Open No. 8-253419 relates to a contact lens solution containing chondroitin sulfate, which is useful for preventing HIV infection. Prior to the present invention, mucopolysaccharides had a high cleaning effect due to the fact that mucopolysaccharides are listed as a component in tears that cause lens stains, and that they have no cleaning effect. It has never been known that it is useful as a component of a lens solution.

The present inventors have found that a specific mucopolysaccharide enhances the cleaning effect, and have completed the present invention. Thus, the present invention provides that chondroitin sulfate and / or hyaluronic acid have no
It is based on an unexpected finding that it has an effect of enhancing the washing effect of proteolytic enzymes and lipolytic enzymes. Although the cause of such an enhancement effect has not yet been elucidated, for example, the negative charge on the surface of chondroitin sulfate and / or hyaluronic acid is likely to release contaminants having a mainly positive charge such as lysozyme on the lens surface. Is considered to promote or facilitate the enzymatic reaction to the contaminant.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The solution for contact lenses of the present invention can be used as a washing and preserving solution for contact lenses. One embodiment of the present invention is a solution for rubbing contact lenses, and another embodiment is a solution for immersion cleaning of contact lenses. When rubbing is performed, the solution of the present invention containing an enzyme and chondroitin sulfate and / or hyaluronic acid or a salt thereof is directly applied to a contact lens and rubbed. In order to carry out immersion cleaning, the immersion cleaning liquid of the present invention obtained by diluting the liquid preparation containing the enzyme with the liquid preparation containing chondroitin sulfate and / or hyaluronic acid or a salt thereof, the enzyme and chondroitin sulfate, And / or a dip and wash solution containing hyaluronic acid or a salt thereof and used without dilution, and a solution containing an enzyme and chondroitin sulfate and / or hyaluronic acid or a salt thereof diluted with physiological saline or the like. The contact lens is immersed in the immersion cleaning solution or the like for an appropriate time. However, the present invention is not limited to the above embodiment, and encompasses any form of contact lens solution provided that it contains an enzyme and chondroitin sulfate and / or hyaluronic acid or a salt thereof. Further, the liquid preparation of the present invention is highly safe, is useful not only for cleaning but also as a contact lens preservation liquid, and is a liquid preparation for contact lenses having a wide range of uses.

[0008] The liquid preparation of the present invention may contain any proteolytic enzyme and / or lipolytic enzyme that is ophthalmically acceptable and useful for decomposing and removing contaminants from contact lenses. Proteolytic enzymes, depending on their active site,
It is roughly classified into four types: serine protease, metalloprotease, thiol protease, and carboxyl protease. In the present invention, a serine protease produced by Bacillus is most effectively used. Specifically, "Clear Lens Pro" (manufactured by Novo Nordisk Bioindustry Japan KK), "Bioprase" (manufactured by Nagase Seikagaku Corporation), "Alkaline Protease"
(Manufactured by Kyowa Enzyme Co., Ltd.), "Protease N" Amano "" (manufactured by Amano Pharmaceutical Co., Ltd.) and the like can be appropriately selected from these and used. Examples of the lipolytic enzyme include lipases derived from Aspergillus, Streptomyces, and Bacillus. Regarding the concentration of the enzyme in the liquid preparation, whether the liquid preparation is used as it is or in the case of diluting it, an appropriate range may be selected depending on the washing ability of the enzyme to be used, and those skilled in the art can arbitrarily select the concentration. And can be implemented. However, usually, both the proteolytic enzyme and the lipolytic enzyme are added at a ratio of 0.001 to 10% by weight. Preferred concentrations are from 0.01 to 10.
% By weight. If the concentration is lower than this, the cleaning effect is not sufficient, and if the concentration is higher, there is a problem in safety. When a solution containing an enzyme is used after being diluted, usually, one to several drops of the enzyme-containing solution is dropped into the solution for dilution, and 20 to 10 times.
Dilute about 0 times. For this purpose, a generally used contact lens storage case or the like can be used. For example, an appropriate amount of a diluting solution is put in a storage case, and one to several drops of an enzyme solution are dropped to obtain an appropriately diluted immersion cleaning solution.

The liquid preparation of the present invention contains chondroitin sulfate, hyaluronic acid or a salt thereof. Examples of the salt include metal salts such as a sodium salt and a potassium salt. These can be obtained as commercial products from Seikagaku Corporation or the like. The content of chondroitin sulfate and / or hyaluronic acid or a salt thereof in the contact lens solution is preferably 0.001% to 10%, particularly preferably 0.01% to 1%. In addition, chondroitin sulfate and / or hyaluronic acid have a molecular weight of tens of thousands to several millions, but if the molecular weight is too high, washing is hindered due to viscosity. . Particularly preferred are those having a molecular weight of tens of thousands to three million.

The liquid preparation of the present invention may contain other components such as a bactericide, a surfactant, and a polyhydric alcohol. If bacteria adhere to or grow on contact lenses, they may cause eye infections. Therefore, a liquid formulation containing a bactericide is useful for preventing such infections. In particular, in the case of a hydrated contact lens, bacteria are liable to grow, so daily sterilization is required. Therefore, a liquid agent that can be washed and sterilized is desirable. However, since a sterilizing agent inhibits the cleaning effect of an enzyme, it has conventionally been difficult to obtain a liquid agent that can simultaneously perform cleaning and sterilization. However, the liquid preparation containing chondroitin sulfate and / or hyaluronic acid or a salt thereof according to the present invention has an enhanced cleaning effect, as shown in the test examples described below. Can also exert a sufficient cleaning effect and are highly useful.
Therefore, the present invention also provides a contact lens solution containing a bactericide. Examples of fungicides include oxidizing agents such as hydrogen peroxide, biguanides such as chlorhexidine, polyhexamethylene biguanide or a salt thereof, α-4- [1-tris (2-hydroxyethyl) ammonium-2-butenyl chloride. And bactericides such as quaternary ammonium salts such as poly [1-dimethylammonium chloride-2-butenyl] -ω-tris (2-hydroxyethyl) ammonium chloride. A preferred fungicide is polyhexamethylene biguanide or a salt thereof and α-4- [1-tris (2-hydroxyethyl) ammonium chloride-2-butenyl] poly [1-dimethylammonium chloride-2-butenyl] -ω-tris ( 2-hydroxyethyl) ammonium chloride. The concentration of the fungicide to be added should be 0.1 so that the washing activity of the enzyme is not inhibited by the high concentration of the fungicide.
00001% -0.1% is preferable, and 0.0001%-
0.05% is more preferable. Further, particularly preferable concentration is 0.00001 to 0.001% in the case of polyhexamethylene biguanide or a salt thereof, and α-4-
[1-Tris (2-hydroxyethyl) ammonium chloride-2-butenyl] poly [1-dimethylammonium chloride-
2-butenyl] -ω-tris (2-hydroxyethyl)
In the case of a quaternary ammonium salt such as ammonium chloride,
0.0001 to 0.01%. These fungicides are:
Commercial products can be used as appropriate.

Further, when an anionic surfactant, an amphoteric surfactant or a nonionic surfactant is added to the liquid preparation of the present invention, the cleaning effect can be further enhanced. The amount of the surfactant is preferably 0.01 to 10 in the concentration of the liquid agent (a mixed solution when diluted) applied to the contact lens.
%, Particularly preferably 0.1 to 5%. If the concentration is too low, the expected enzyme stabilizing effect and detergency cannot be obtained, and if the concentration is too high, there is a risk of causing skin damage.

Examples of the anionic surfactant include alkyl sulfates, polyoxyethylene alkyl ether sulfates,
N-acyl amino acid salts, polyoxyethylene alkyl ether acetates, alkyl sulfocarboxylates, α-olefin sulfonates, polyoxyethylene alkyl ether phosphates and the like. Examples of the amphoteric surfactant include betaine alkyldimethylaminoacetate, betaine fatty acid amidopropyldimethylaminoacetate, and alkylpolyaminoethylglycine. Non-ionic surfactants include polyoxyethylene polyoxypropylene alkyl ether, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene glycerin Fatty acid esters, polyethylene glycol, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkylamine, polyoxyethylene fatty acid amide, and the like.

Further, by using a metal chelating agent in the liquid preparation of the present invention, the cleaning effect can be enhanced. Examples of the metal chelating agent include edetic acid and edetate (disodium edetate, calcium disodium edetate, trisodium edetate, tetrasodium edetate) and the like. Specific examples of the metal chelating agent include ethylenediaminetetraacetic acid, nitrilotriacetic acid and salts thereof, and the content thereof is preferably 0.01% to 1% in the mixture.
Particularly preferably, the content is 0.05% to 0.5%.

Furthermore, the enzyme stability can be further enhanced by blending a polyhydric alcohol with the liquid preparation of the present invention. Specific examples of the polyhydric alcohol include glycerin, diethylene glycol, propylene glycol, polyethylene glycol, sorbitol and the like. Particularly preferred polyhydric alcohols are glycerin, polyethylene glycol and propylene glycol which are excellent not only in stabilizing the enzyme but also in removing lipid stains. It is effective to mix the polyhydric alcohol in the mixed solution in an amount of 0.5 to 4.0%. When the polyhydric alcohol concentration is 4.0% or more, the physical properties of the contact lens may be affected.

The liquid preparation of the present invention may contain a buffer usually used in the art, for example, boric acid, phosphoric acid, carbonate,
A buffer such as citric acid, tartaric acid, lactic acid, acetic acid, and phthalic acid can be used. In the liquid preparation of the present invention, a boric acid-based or phosphate-based buffer is preferable, and a boric acid-based buffer is more preferable in terms of stabilizing enzymes and enhancing bactericidal activity. Also,
The concentration of the buffer may be any concentration that keeps the enzyme stable,
0.01-20% can be blended. If it is less than 0.01%, the buffering power and the stability of the enzyme will be low, and if it is more than 20%, the physical properties of the contact lens may be adversely affected.

The contact lens solution of the present invention is useful as a detergent and a preservative, and usually has a pH of preferably 4 to 9, and particularly preferably a pH of 6 to 8. In addition, as long as the cleaning effect of the liquid preparation of the present invention is not impaired, in addition to the components described above, a preservative, a pH adjuster, an isotonic agent,
Necessary components known in the art such as surfactants, amino acids, preservatives, and inorganic salts can be appropriately blended.
Examples of preservatives include sorbic acid, potassium sorbate, paraoxybenzoates, chlorhexidine gluconate, benzalkonium chloride, benzethonium chloride and the like. Examples of the pH adjuster include hydrochloric acid, acetic acid, and sodium hydroxide, and examples of the tonicity agent include glycerin, glucose, and mannitol. Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited thereto.

Examples 1 to 6

[Table 1] The components of each formulation described in Table 1 are mixed to prepare a liquid preparation.
The liquids of Examples 1 to 6 can be used as liquids for scrubbing. Further, the liquid preparations of Examples 1 to 3 can be appropriately diluted with a diluting liquid such as physiological saline to prepare a immersion liquid preparation. The liquid preparation of each example was prepared by adding purified water.

Examples 7 to 18

[Table 2] Enzyme-containing solutions A, B, and C shown in Table 2 and polysaccharide-containing solutions D, E, F, and G for dilution are separately prepared. These enzyme solutions and diluents are arbitrarily combined to obtain a immersion cleaning solution. Each liquid was prepared using purified water.

Test Example 1 Detergent Effect Test of Liquid Preparations A test liquid obtained by diluting the enzyme solution A shown in Table 2 25 times with the diluent E, and the enzyme solution A obtained by removing the chondroitin sulfate from the diluent E A comparative solution obtained by similarly diluting the solution was used. 1.0 g of ovalbumin, 0.1 g of lysozyme chloride and 0.1 g of swine stomach mucin were weighed from the artificial tears, and 100 g
Dissolved in phosphate buffer (ml) to make pH = 7.2, and 5 ml of this solution was used with an unused contact lens (Breath- ^OTM Toray) or a contact lens (1 Day AcuVue ^™ Johnson & Johnson). It was immersed and shaken at 37 ° C. for about 8 hours. Rinse the excess artificial tears in the lens with saline and test or control 1.
Immerse it in a lens case (manufactured by Ginza Planning Co., Ltd.) with 5 ml and boil it with a boiling device (manufactured by Ginza Planning Co., Ltd.).
Soaked for hours. This operation was repeated three times with a new solution. In the lens, excess artificial tears were rinsed with physiological saline, and immersed in a lens case (manufactured by Ginza Planning Co., Ltd.) for about 15 hours together with 1.5 ml of a test solution or a comparative solution. This operation was repeated three times with a new test solution, and finally, after rinsing with saline, the condition of the lens was visually observed. Table 3 shows the results.

[Table 3] Evaluation: 汚 れ There is almost no dirt visible. ○ Slightly visible dirt remains. △ A considerable amount of dirt that can be seen visually remains. The results in Table 3 show that the liquid of the present invention has a high cleaning effect.

Continued on the front page F term (reference) 2H006 DA08 4C058 AA09 BB07 JJ07 JJ08 4H003 BA12 DA16 EA02 EA18 EB12 EB16 EB19 EB34 EB41 EC01 EC02 ED28 FA01 FA34

Claims (8)

[Claims] 1. A contact lens solution containing a protease and / or a lipolytic enzyme and chondroitin sulfate and / or hyaluronic acid or a salt thereof. 2. The liquid preparation according to claim 1, wherein chondroitin sulfate and / or hyaluronic acid or the concentration thereof is 0.01 to 1% by weight. 3. The liquid preparation according to claim 1, further comprising a bactericide. 4. The bactericide is polyhexamethylene biguanide or a salt thereof, or α-4- [1-tris (2-hydroxyethyl) ammonium chloride-2-butenyl] poly [1-dimethylammonium chloride-2-butenyl]. The liquid preparation according to claim 3, which is -ω-tris (2-hydroxyethyl) ammonium chloride. 5. Polyhexamethylene biguanide or a salt thereof, or α-4- [1-tris (2-hydroxyethyl)
Ammonium chloride-2-butenyl] poly [1-dimethylammonium chloride-2-butenyl] -ω-tris (2-hydroxyethyl) ammonium chloride has a concentration of 0.000.
The liquid preparation according to claim 4, wherein the amount is from 0.01 to 0.1%. 6. The liquid preparation according to claim 1, further comprising one or more substances selected from a nonionic surfactant, an amphoteric surfactant, an anionic surfactant and a chelating agent. 7. The liquid preparation according to claim 1, further comprising glycerin, propylene glycol or polyethylene glycol. 8. The liquid preparation according to claim 1, which is used for scrubbing or immersion cleaning of a contact lens.