JP4247546B2 - Polysaccharide-containing contact lens solution - Google Patents

Description

  The present invention relates to a liquid agent having excellent detergency for contact lenses, particularly soft contact lenses and oxygen-permeable hard contact lenses.

  A contact lens is a medical device that is directly inserted into the eye, but due to its wearing, adherence of dirt derived from living bodies such as proteins, lipids, and inorganic salts is inevitable. In addition, since contact lenses are handled by fingers, there are many cases where contaminants such as cosmetics, hand creams and hair sprays are attached from outside the body. If these stains are left unattended, the permeability of the lens will be reduced and it will be difficult to see, not only the feeling of wearing will be worsened, but also the oxygen permeability will be reduced, shortening the life of the contact lens, and infectious diseases, etc. May have a negative effect.

  Contact lenses are broadly divided into hard contact lenses and soft contact lenses, but hard contact lenses with good oxygen permeability and hydrous soft contact lenses that have been developed with the aim of better wearing feeling in recent years are especially characterized by their material characteristics. Since dirt easily adheres, it is important to remove contaminants in order to take advantage of its excellent characteristics.

  In order to remove adhering protein and fat stains, there are methods using proteolytic enzymes and lipolytic enzymes, 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 scrubbing in the solution or appropriately diluting the enzyme solution and immersing it in the diluted solution is employed.

  However, in the case of enzyme-containing liquids for scrubbing, it is important to stably store water-unstable enzymes, and not only a sufficient detergency cannot be obtained, but also the cleaning effect of the enzyme is reduced. There was a fear. Thus, in order to compensate for the sufficient cleaning effect, the use of a strong surfactant and physical cleaning with an abrasive may be taken into account, but this is not always desirable from the viewpoint of safety.

  On the other hand, in the case of the enzyme-containing solution for immersion cleaning, the cleaning effect is not sufficient for the adhered dirt, and the cleaning effect varies because the dilution rate is not accurate.

  As a result of intensive studies aimed at providing an enzyme-containing liquid for contact lenses that has a high cleaning effect and is safe, the present inventors have obtained a proteolytic enzyme and / or a lipolytic enzyme and a certain polysaccharide. The present invention has been completed by finding that a solution for contact lenses suitable for the above purpose and having a high cleaning effect and safety can be obtained by containing them together.

Accordingly, the present invention provides the following.
(1) A contact lens solution containing a proteolytic enzyme and / or a lipolytic enzyme and chondroitin sulfate and / or hyaluronic acid or a salt thereof.
(2) The liquid preparation according to item (1) or (2), wherein chondroitin sulfate and / or hyaluronic acid or a concentration thereof is 0.01 to 1% by weight.
(3) The liquid agent according to item (1) or (2), which further contains 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] -ω The liquid agent according to item (3), which is 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 ( The liquid agent according to item (4), wherein the concentration of 2-hydroxyethyl) ammonium chloride is from 0.0001 to 0.1%.
(6) The liquid agent according to item (1), which further contains one or more substances selected from nonionic surfactants, amphoteric surfactants, anionic surfactants and chelating agents.
(7) The liquid agent according to item (1), which further contains glycerin, propylene glycol or polyethylene glycol.
(8) The liquid agent according to any one of items (1) to (7), which is used for rubbing or immersion cleaning of contact lenses.

  That is, the present invention provides a solution for contact lenses containing a proteolytic enzyme and / or a lipolytic enzyme and chondroitin sulfate and / or hyaluronic acid or a salt thereof.

  Polysaccharides such as chondroitin sulfate and hyaluronic acid are also components in tears, and contact lens disinfectants and contact lens preservatives containing these are known (Japanese Patent Laid-Open Nos. 63-59960 and 8-253419). . However, Japanese Patent Application Laid-Open No. 63-59960 only describes that chondroitin sulfate sodium prevents the disinfectant component from adsorbing to the contact lens and suppresses the change in physical properties of the contact lens. Kaihei 8-253419 relates to a contact lens solution useful for prevention of HIV infection containing chondroitin sulfate. Prior to the present invention, mucopolysaccharides have a high cleaning effect because mucopolysaccharides are listed as components in tears that cause lens contamination, and because they have no cleaning effect. It has not been known at all to be useful as a component of a lens solution.

  The present inventors have found that specific mucopolysaccharides enhance the cleaning effect and have completed the present invention. Thus, the present invention is unexpected that chondroitin sulfate and / or hyaluronic acid has the effect of enhancing the cleaning effect of proteolytic enzymes and lipolytic enzymes, even though it does not have a cleaning effect itself. It is based on the knowledge of. 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 can easily remove contaminants having a positive charge such as lysozyme on the lens surface. Therefore, it is considered that the enzyme reaction to the pollutant is promoted or easily caused.

  The contact lens solution of the present invention can be used as a cleaning and storage solution for contact lenses. One embodiment of the present invention is a contact lens scrubbing solution, and another embodiment is a contact lens immersion cleaning solution.

  In carrying out the rubbing, the solution of the present invention containing an enzyme and chondroitin sulfate and / or hyaluronic acid or a salt thereof is directly applied to the contact lens and rubbed.

  In order to carry out immersion cleaning, the immersion cleaning solution obtained by diluting the enzyme-containing solution of the present invention with a solution containing chondroitin sulfate and / or hyaluronic acid or a salt thereof, the enzyme and chondroitin sulfate, and Dilute cleaning solution that contains hyaluronic acid or salts thereof and that is used without dilution, and a solution that contains enzymes and chondroitin sulfate and / or hyaluronic acid or salts thereof diluted with physiological saline or the like The contact lens is immersed in an appropriate immersion cleaning solution for an appropriate time.

  However, the present invention is not limited to the above-described embodiment, and includes 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 and useful as a contact lens preserving liquid as well as cleaning, and is a contact lens liquid having a wide range of uses.

  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 of contact lenses.

  Proteolytic enzymes are roughly classified into four types according to their active sites: serine protease, metalloprotease, thiol protease, and carboxyl protease. In the present invention, serine protease produced by Bacillus is most effectively used. Specifically, “Clear Lens Pro” (manufactured by Novo Nordisk Bio Industry Japan Co., Ltd.), “Bioplase” (manufactured by Nagase Seikagaku Corporation), “Alkaline Protease” (manufactured by Kyowa Enzyme), “Protease N” There are “Amano” (manufactured by Amano Pharmaceutical Co., Ltd.) and the like, which can be appropriately selected and used.

  Examples of the lipolytic enzyme include lipases derived from the genera Aspergillus, Streptomyces, and Bacillus.

  The concentration of the enzyme in the liquid agent may be selected within the appropriate range according to the washing ability of the enzyme used, regardless of whether the liquid agent is used as it is or diluted. And can be implemented.

  However, normally, both proteolytic enzyme and lipolytic enzyme are blended at a ratio of 0.001 to 10% by weight. A preferred concentration is 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 terms of safety.

  Moreover, when diluting and using the liquid agent containing an enzyme, normally 1 to several drops of enzyme-containing liquid agents are dripped at the liquid agent for dilution, and are diluted about 20 to 100 times. For this purpose, a commonly used contact lens storage case or the like can be used. For example, an appropriately diluted immersion cleaning liquid can be obtained by adding an appropriate amount of a diluting liquid into a storage case and dropping one to several drops of the enzyme liquid.

  The liquid preparation of the present invention contains chondroitin sulfate and hyaluronic acid or their salts. Examples of the salt include metal salts such as sodium salt and potassium salt. These can be obtained as commercial products from Seikagaku Corporation. The content of chondroitin sulfate and / or hyaluronic acid or a salt thereof in the contact lens solution is preferably 0.001% to 10%, and particularly preferably 0.01 to 1%. In addition, chondroitin sulfate and / or hyaluronic acid has molecular weights of tens of thousands to millions, but if the molecular weight is too high, the molecular weight is preferably 5 million or less in order to inhibit washing due to viscosity. . Particularly preferred are those having a molecular weight of tens of thousands to three millions.

  Further, the liquid preparation of the present invention can contain other components such as a bactericidal agent, a surfactant, and a polyhydric alcohol.

  When bacteria adhere to and proliferate on contact lenses, it may cause ocular infections. Therefore, a liquid preparation containing a bactericidal agent is useful. In particular, in the case of a hydrous contact lens, since bacteria are likely to grow, daily sterilization is necessary. Therefore, a liquid agent that can be cleaned and sterilized is desirable. However, since the bactericidal agent inhibits the cleaning effect of the enzyme, it has been difficult to obtain a liquid agent that can be simultaneously cleaned and sterilized. 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 later, and therefore contains an enzyme together with a bactericidal agent. Can exhibit a sufficient cleaning effect and is highly useful.

  Therefore, the present invention also provides a contact lens solution containing a bactericidal agent.

  Examples of bactericides include oxidizing agents such as hydrogen peroxide, biguanides such as chlorhexidine, polyhexamethylene biguanide or its salts, α-4- [1-tris (2-hydroxyethyl) ammonium chloride-2-butenyl There are bactericides such as quaternary ammonium salts such as poly [1-dimethylammonium chloride-2-butenyl] -ω-tris (2-hydroxyethyl) ammonium chloride. Preferred fungicides are polyhexamethylene biguanide or its salts 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 bactericidal agent to be blended is preferably 0.0001% to 0.1%, more preferably 0.0001% to 0.05% so that the cleaning activity of the enzyme is not inhibited by a high concentration bactericidal agent. The particularly preferred 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. In the case of a quaternary ammonium salt such as poly [1-dimethylammonium chloride-2-butenyl] -ω-tris (2-hydroxyethyl) ammonium chloride, it is 0.0001 to 0.01%. As these bactericides, commercially available products can be used as appropriate.

  Furthermore, 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 such that the concentration in the liquid agent (mixed liquid when diluting) applied to the contact lens is preferably 0.01 to 10%, particularly preferably 0.1 to 5%. is there. If the concentration is too low, the expected enzyme stabilizing effect and detergency cannot be obtained. If the concentration is too high, there is a risk of causing skin damage.

  Examples of the anionic surfactant include alkyl sulfate, polyoxyethylene alkyl ether sulfate, N-acyl amino acid salt, polyoxyethylene alkyl ether acetate, alkyl sulfocarboxylate, α-olefin sulfonate, polyoxy Examples include ethylene alkyl ether phosphate.

  Examples of amphoteric surfactants include alkyldimethylaminoacetic acid betaine, fatty acid amidopropyldimethylaminoacetic acid betaine, and alkylpolyaminoethylglycine.

  Nonionic surfactants include polyoxyethylene polyoxypropylene alkyl ether, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbit fatty acid ester, polyoxyethylene glycerin. Examples include fatty acid esters, polyethylene glycol, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkylamine, and polyoxyethylene fatty acid amide.

  Moreover, a cleaning effect can be improved by using a metal chelating agent for the liquid agent of this invention. Examples of the metal chelating agent include edetic acid, edetate (edetate disodium, edetate calcium disodium, edetate trisodium, edetate tetrasodium) 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 mixed solution, particularly preferably 0.0%. 05% to 0.5%.

  Furthermore, enzyme stability can be further improved by mix | blending a polyhydric alcohol with the liquid agent of this 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 or propylene glycol, which are excellent not only for stabilizing the enzyme but also for cleaning the lipid soil. It is effective to add the polyhydric alcohol in the liquid mixture in an amount of 0.5 to 4.0%. If the polyhydric alcohol concentration is 4.0% or more, the physical properties of the contact lens may be affected.

  In the liquid preparation of the present invention, a buffer agent usually used in the technical field, for example, a boric acid type, phosphoric acid type, carbonic acid type, citric acid type, tartaric acid type, lactic acid type, acetic acid type, phthalic acid type buffering agent, etc. Can be used. In the liquid preparation of the present invention, a boric acid-based or phosphoric acid-based buffer is preferable, and a boric acid-based is more preferable in terms of stabilizing the enzyme and enhancing the bactericidal power. Moreover, the density | concentration of a buffer should just be a density | concentration which keeps an enzyme stable, and can mix | blend 0.01 to 20%. If it is 0.01% or less, the buffering power and the stability of the enzyme are low, and if it is higher than 20%, the physical properties of the contact lens may be adversely affected.

  The liquid agent for contact lenses of the present invention is useful as a cleaning agent and a preservative, and usually has a pH of preferably 4 to 9, and particularly preferably pH 6 to 8.

  Moreover, as long as the cleaning effect of the liquid preparation of the present invention is not impaired, in addition to the components described above, in the technical field such as preservatives, pH adjusters, tonicity agents, surfactants, amino acids, preservatives, inorganic salts, etc. Known necessary components 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 adjusting agent include hydrochloric acid, acetic acid, sodium hydroxide and the like, and examples of the isotonic agent include glycerin, glucose, mannitol and the like.

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

  Examples 1-6

The ingredients of each formulation described in Table 1 are mixed to prepare a liquid. The solutions of Examples 1 to 6 can be used as a scrubbing solution.
In addition, the solutions of Examples 1 to 3 can be appropriately diluted with a diluting solution such as physiological saline to obtain a dipping solution. The liquid agent of each Example was prepared by adding purified water.

  Examples 7-18

  Enzyme-containing solutions A, B, and C shown in Table 2 and dilution solutions D, E, F, and G containing polysaccharides are prepared separately. A solution for immersion cleaning is obtained by arbitrarily combining the enzyme solution and the diluted solution. Each solution was prepared with purified water.

  Test Example 1 Detergent effect test of solution The test solution obtained by diluting the enzyme solution A described in Table 2 25 times with the diluent E, and the solution obtained by removing the chondroitin sulfate sodium from the diluent E A comparative solution obtained by diluting was used.

Weigh 1.0 g of ovalbumin, 0.1 g of lysozyme chloride and 0.1 g of porcine stomach mucin, dissolve it in 100 ml of phosphate buffer to make pH = 7.2, and use it in 5 ml of this solution. Contact lens (1) (manufactured by Breath Oh ^TM Toray) or contact lens (2) (manufactured by 1 Day Accuview ^TM Johnson & Johnson) was immersed and shaken at 37 ° C. for about 8 hours.

  Excess artificial tears from the lens (1) are rinsed with physiological saline, immersed in a lens case (Ginza Planning Co., Ltd.) together with 1.5 ml of the test solution or comparison solution, and boiled in a boiling machine (Ginza Planning Co., Ltd.). And was further immersed for about 15 hours. This operation was repeated 3 times by exchanging with a new liquid.

  In the lens (2), excess artificial tears were rinsed with physiological saline and immersed in a lens case (Ginza Planning Co., Ltd.) for about 15 hours together with 1.5 ml of a test solution or a comparison solution. This operation was repeated three times by exchanging with a new test solution. Finally, after rinsing with saline, the state of the lens was visually observed. The results are shown in Table 3.

Evaluation: ◎ There is almost no dirt that can be visually observed.
○ Some dirt remains visually.
△ A considerable amount of dirt remains visually.
The result of Table 3 has shown that the cleaning effect of the liquid agent of this invention is high.

Claims (4)

A two-component solution containing an enzyme-containing solution containing a serine protease and a diluting solution containing chondroitin sulfate and / or hyaluronic acid or a salt thereof separately and used by diluting the enzyme-containing solution with the diluting solution Type of contact lens solution. The liquid agent according to claim 1, wherein the chondroitin sulfate and / or hyaluronic acid is set to 0.01 to 1% by weight in the contact lens solution at the time of use. The liquid preparation according to claim 1, wherein the enzyme-containing liquid preparation also contains glycerin. The liquid agent according to any one of claims 1 to 3 , which is used for rubbing or immersion cleaning of contact lenses.