JP4781398B2 - Contact lens solution - Google Patents

Description

  The present invention relates to a liquid agent for contact lenses. By using a specific polyol, the present invention exhibits an excellent antiseptic or disinfecting effect without using a conventionally used disinfectant and also has safety for eyes. The present invention relates to a sufficiently prepared contact lens solution. The present invention also relates to a contact lens solution in which the polyol stabilizes a proteolytic enzyme effective for cleaning a contact lens in a liquid state for a long period of time.

  Since contact lenses are used in direct contact with human eyes, in order to wear them safely and comfortably, it is necessary to periodically perform cleaning, disinfection and the like. The contact lens is contaminated with components in the tear fluid or during handling with fingers, and if this is left to be used as it is, it is expected to adversely affect the cornea and conjunctiva. In addition, microorganisms such as bacteria may grow while the contact lens is stored due to these stains, and these microorganisms may cause eye infections and the like.

  Conventionally, contact lenses have been treated with individual solutions depending on the purpose, but in recent years, all of cleaning, storage, disinfection, etc. are performed with one solution for the convenience of the user. Multi-purpose liquids are becoming mainstream. This solution contains a surfactant to remove dirt from the contact lens and a disinfectant to give a disinfectant or antiseptic effect. Of course, this solution remains in the eye while attached to the contact lens. Designed to be safe to enter. In the case of liquids for hard contact lenses, bactericides are added mainly to maintain the antiseptic effect within the period of use of the liquid, but after washing and storage with the liquid, Since it is recommended to rinse the lens with water before wearing it, the prescription decision was made that there was no adsorption or accumulation of disinfectant or the like on the lens. On the other hand, for liquid preparations for soft contact lenses, since disinfection of lenses is obligatory, liquid chemicals have been required to have a disinfection effect, and recently, chemical disinfectants that do not rely on heat, which is a simple method, have become popular. is doing. Soft lenses cannot be rinsed with tap water before wearing (the lens that has been rinsed with tap water is adsorbed to the cornea due to the treatment with a solution that cannot guarantee sterility after disinfection and osmotic pressure). It is essential that the liquid is safe even if it is brought into the eye as it is.

  As the disinfectant, one having high safety per se is selected, and the necessary minimum use is made in consideration of disinfecting effect, antiseptic effect and safety in prescription. For example, in chemical disinfectants for soft contact lenses, high molecular weight quaternary ammonium or biguanide is generally used, and because of its high molecular weight, it is designed to prevent the disinfectant from entering the lens material. In addition, a nonionic surfactant that does not cause eye irritation is used as a cleaning component. However, it is difficult to divert this chemical disinfectant formulation as it is to a liquid solution for hard contact lenses for the following reasons.

  First of all, due to the characteristics of the lens material, lipid-based stains derived from eye grease and fingers are likely to adhere to the lens due to the characteristics of the lens material. In order to remove these stains sufficiently, nonionic surfactants are used. It is preferable to use an anionic surfactant in addition to the agent, but then cationic bactericides (benzalkonium chloride, chlorhexidine, quaternary ammonium, biguanide, etc.) used in the soft contact lens solution are anionic surfactants. The disinfection effect cannot be expressed in the presence of agents. Examples of conventionally used bactericides include sorbic acid and formaldehyde donors. These are basically used on the premise that the lens is rinsed with tap water after treatment, with sorbic acid adsorbing to the lens material, and formaldehyde with the disinfectant's confidence in safety. There is a risk of being carried out.

  Second, due to surface hydrophilization treatment, dirt derived from proteins and the like is likely to adhere, and for hard contact lenses that are generally used over a long period of time compared to soft contact lenses, dirt is completely removed. It is preferable to use an enzyme agent together because it is more required to be removed. There are three types of enzyme agents: a type that is mixed at the time of use, a type that is stored separately until the time of purchase, a type that is continuously used after mixing at the start of use, and a type that is mixed from the beginning. As a recent trend, the mixed type at the time of purchase or the type that is mixed from the beginning is preferred over the type that is mixed at the time of use, but in these cases, the enzyme activity in the liquid preparation is somewhat longer. It is required to maintain the period.

  Thirdly, in the case of hard contact lenses, a thickener is added to the solution to protect the lens surface and to prevent scratches and to prevent scratching with a fingertip or palm. There are various differences from a liquid agent for treating a soft contact lens, such as improving the slipperiness of the lens being cleaned by adding (especially an anionic surfactant). Because of these differences, it is difficult to use both the soft contact lens solution and the hard contact lens solution, and the respective target solutions have been prepared individually.

  By the way, for soft contact lens liquids, the above-mentioned multipurpose liquids have been introduced into the market, but under the same concept, liquids that can be used for multipurposes in hard contact lenses have also been developed. In order to achieve this, there is a need for a bactericidal agent that exhibits antiseptic or disinfecting effects even when the various compositions (for example, anionic surfactants, enzymes, thickeners, etc.) are blended. It is. At the same time, when an enzyme is added to the solution, it is necessary to prepare a solution that can maintain its storage stability.

The following are given as prior art related to the present invention.
JP-A-8-29744 JP-A-9-241696 Japanese Patent Laid-Open No. 1-180515 JP-A-4-143718

  The present invention has been made in the background of the above-described circumstances, and the problem to be solved is that, even in the presence of various compositions, a sufficient antiseptic or disinfecting effect can be expressed. An object of the present invention is to provide a contact lens solution containing a bactericide that is highly safe for eyes. At the same time, when a proteolytic enzyme is added to the solution as a multipurpose contact lens solution, a solution that enables long-term maintenance of the enzyme activity is provided.

  As a result of intensive studies to solve the above problems, the present inventor has developed a high antiseptic and disinfecting effect without using a conventional disinfectant by combining a surfactant and a specific polyol. It has been found that the enzyme activity can be maintained by combining a proteolytic enzyme and the specific polyol, and the present invention has been completed.

  That is, the present invention relates to 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,5-pentanediol, cyclopentane1,2-diol or 1,2-hexanediol, 3-hexanediol, 1,4-hexanediol, 1,5-hexanediol, 1,6-hexanediol, 2-methyl-2,4-pentanediol, cyclohexane-1,3-diol, 1,2,6 At least one selected from the group consisting of hexanetriol, methylcyclohexane-1,2,4-triol, cyclohexane-1,2,4,5-tetrol and a polyol having 5 to 6 carbon atoms, 0.01 to A contact lens solution characterized by containing 3.0 (w / v)% surfactant, and its excellent cleaning effect and The gist of the present invention is a multipurpose type liquid agent having a disinfecting effect for contact lenses by combining the polyol with the polyol.

  In the contact lens solution according to the present invention, the polyol is preferably adjusted to a concentration range of 0.1 to 5.0 (w / v)% and contains a sequestering agent. By using it in the above-mentioned concentration range, it is possible to obtain a contact lens solution having a disinfecting effect without using a conventional disinfectant while having excellent detergency against lipid stains adhering to the contact lens.

  Further, a liquid enzyme agent containing an effective amount of a proteolytic enzyme for washing contact lenses and 20 to 90 (w / v)% polyhydric alcohol is added to the liquid agent, and the liquid enzyme agent is added to 10 parts. By diluting up to 200 times, protein stains adhering to the contact lens can be effectively removed.

  One of the preferred embodiments of the present invention includes 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,5-pentanediol, cyclopentane1,2-diol, 2-hexanediol, 1,3-hexanediol, 1,4-hexanediol, 1,5-hexanediol, 1,6-hexanediol, 2-methyl-2,4-pentanediol, cyclohexane-1,3- One selected from the group consisting of diol, 1,2,6-hexanetriol, methylcyclohexane-1,2,4-triol, cyclohexane-1,2,4,5-tetrol and a polyol having 5 to 6 carbon atoms A liquid for contact lenses comprising the above and an effective amount of a proteolytic enzyme for cleaning the contact lens And the like. As described above, the polyol has an effect of providing a disinfecting effect to the solution, and in particular, has an effect of stabilizing the activity of the proteolytic enzyme over a long period of time and maintaining the cleaning effect on the protein stain of the contact lens solution. . This solution is preferably mixed with boric acid or a salt thereof.

  When the enzyme-containing solution of the above embodiment is used by mixing with another contact lens solution (two-component mixed type), the polyol concentration of the present invention is blended in the range of 20 to 90 (w / v)%. In addition, boric acid or a salt thereof is preferably used in the range of 0.001 to 10 (w / v)%. On the other hand, when a proteolytic enzyme is blended from the beginning of shipment and used as it is (one-pack type), the polyol can be used at a low concentration. In this case, the polyol concentration is in the range of 0.1 to 15 (w / v)%, and boric acid or a salt thereof is used in the range of 0.001 to 10 (w / v)%.

  Furthermore, as an embodiment of the present invention, among the above specific polyols, 1,2-hexanediol having a hydroxyl group at the 1- and 2-positions of hexane is the most preferred component for achieving the object of the present invention. This substance exhibits an excellent action in both the disinfection effect and the stabilization effect of the proteolytic enzyme, and can be suitably used as a liquid for contact lenses as a highly safe component.

  The contact lens solution of the present invention contains 1,2-pentanediol, 1,3-pentanediol even when it contains an anionic surfactant that inhibits the disinfecting effect of commonly used cationic fungicides. Pentanediol, 1,4-pentanediol, 1,5-pentanediol, cyclopentane1,2-diol or 1,2-hexanediol, 1,3-hexanediol, 1,4-hexanediol, 1,5- Hexanediol, 1,6-hexanediol, 2-methyl-2,4-pentanediol, cyclohexane-1,3-diol, 1,2,6-hexanetriol, methylcyclohexane-1,2,4-triol, cyclohexane -Combining one or more selected from the group of C5-6 polyols consisting of 1,2,4,5-tetrol It provides excellent disinfecting effects, high contact lens cleaning effects, and can provide a highly safe liquid that does not cause problems such as adsorption and accumulation of components on contact lenses. Contact lenses can be cared for safely and easily by lens users.

  In addition, since the specific polyol also has an effect of maintaining proteolytic enzyme activity, it is possible to provide a cleaning solution that can remove protein stains adhering to the contact lens.

  The surfactant used in the contact lens solution according to the present invention is not particularly limited as long as it is highly safe for eyes, but an anionic surfactant is preferably used in view of the cleaning effect. Examples of the anionic surfactant include α-olefin sulfonate, alkyl sulfonate, alkyl benzene sulfonate, carboxylated ether salt having polyoxyethylene chain, alkyl phosphate, alkyl ether phosphorus having polyoxyethylene chain. Examples thereof include acid salts / sulfates, alkyl sulfates, alkyl sulfate ethers, N-acyl taurine salts, N-acyl amino acid salts, alkyl ether carboxylates and the like. These may be used alone or in combination of two or more. Anionic surfactants have excellent detergency against lipid stains, as well as stains from fingers when wearing lenses, as well as dirt derived from eye grease generated while wearing contact lenses. Since the effect is high, rubbing is not required for processing of a normal lens, and a sufficient cleaning effect can be obtained only by dipping. This use concentration is preferably in the range of 0.01 to 3.0 (w / v)%, more preferably 0.02 to 1.0 (w / v)%. When the anionic surfactant concentration is lower than 0.01 (w / v)%, the desired cleaning effect cannot be exhibited, and when it is higher than 3.0 (w / v)%, the cleaning effect is sufficient. This is because there is a possibility that eye irritation due to an unnecessary surfactant may occur. Among these anionic surfactants, α-olefin sulfonates, alkyl ether phosphates / sulfates having polyoxyethylene chains, and alkyl sulfates are particularly preferably used. There are “OS-14” manufactured by Chemicals Co., Ltd., “SBL-4N” manufactured by Nikko Chemicals Co., Ltd., and “Nissanper Soft SP” manufactured by NOF Corporation.

  In addition to the above surfactants, nonionic surfactants and amphoteric surfactants can be added to further improve the cleaning effect and reduce the irritation of the cleaning liquid. Nonionic surfactants include polyoxyethylene glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbit fatty acid esters, polyoxyethylene alkylphenyl formaldehyde condensates , Polyoxyethylene hydrogenated castor oil, polyoxyethylene sterols, polyethylene glycol fatty acid esters, polyoxyethylene polyoxypropylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene alkyl ethers, polyoxyethylene lanolin Examples thereof include alcohols and polyoxyethylene fatty acid amides. Among them, polyoxyethylene is preferable. Those containing alkylene chain structure is employed. Examples of amphoteric surfactants include glycine types such as alkylpolyaminoethylglycine, betaine acetate types such as lauryldimethylaminoacetic acid betaine, imidazoline types, amphoteric surfactants such as alkylaminopropionic acid and alkylaminopropionate, etc. Is mentioned. These use concentrations are preferably in the range of 0.01 to 3.0 (w / v)%, more preferably 0.02 to 1.5 (w / v)%. When the surfactant concentration is lower than 0.01 (w / v)%, the cleaning effect cannot be exhibited. When the surfactant concentration is higher than 3.0 (w / v)%, the cleaning effect is sufficient and more than necessary. This is because the surfactant is used.

In the present invention, a specific polyol having 5 to 6 carbon atoms is used so that a desired antiseptic and disinfecting effect can be exhibited even when an anionic surfactant is used. As described above, the commonly used cationic bactericides can be used in combination with an anionic surfactant to neutralize the cationic group and reduce the action on microorganisms, thereby exhibiting a disinfecting effect. Although not possible, the polyols of the present invention are not subject to such effects. As the disinfectant, there are amphoteric disinfectants, formaldehyde donors, and the like that can be used for contact lenses. However, as will be exemplified later in amphoteric fungicides, the presence of an anionic surfactant inhibits the disinfection effect, and the formaldehyde donor may cause problems such as allergies. In the invention, the polyol was selected. The disinfection effect of polyols has been well known for some time, and some propylene glycol is used as a disinfectant. However, propylene glycol is not always suitable because it has a low molecular weight and thus has high skin permeability and may be perceived as irritation by some users. The polyol of the present invention is a product in which at least two or more hydroxyl groups are bonded to 5 to 6 carbon atoms, and 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,5- Pentanediol, cyclopentane 1,2-diol or 1,2-hexanediol, 1,3-hexanediol, 1,4-hexanediol, 1,5-hexanediol, 1,6-hexanediol, 2-methyl- From the group consisting of 2,4-pentanediol, cyclohexane-1,3-diol, 1,2,6-hexanetriol, methylcyclohexane-1,2,4-triol, cyclohexane-1,2,4,5-tetrol One or more selected. The concentration of the polyol used is preferably in the range of 0.1 to 5.0 (w / v)%, more preferably 1.0 to 4.0 (w / v)%. When the concentration of the polyol is lower than 0.1 (w / v)%, the antiseptic effect is insufficient, and when it exceeds 5.0 (w / v)%, the osmotic pressure of the liquid becomes high, and the lens specifications and surface This is because it may adversely affect the condition.
Among these polyols, 1,2-pentanediol and 1,2-hexanediol are particularly preferable in terms of safety and raw material cost. In addition, since these polyols do not have an anxiety about adsorption | suction to a lens raw material like the case where the conventional ionic disinfectant is used, the liquid agent excellent in safety | security can be provided.

  In the present invention, it is preferable to add a sequestering agent in addition to the anionic surfactant and the specific polyol. In particular, contact lenses are intended to remove such dirt because polyvalent metal ions such as calcium ions, which are lacrimal fluid components, tend to deposit as insoluble salts. The deposited polyvalent metal ions are removed by the sequestering agent contained in the solution of the present invention, and the contact lens is kept clean. The sequestering agent is not particularly limited as long as it is an ophthalmologically acceptable compound. For example, polyvalent carboxylic acids such as ethylenediaminetetraacetic acid, citric acid and tartaric acid, hydroxycarboxylic acids such as gluconic acid, and sodium salts thereof. And salts such as potassium salts. Among these, polyvalent carboxylic acids such as ethylenediaminetetraacetic acid, citric acid, and tartaric acid, and sodium salts and potassium salts thereof are preferable. The concentration of the sequestering agent is preferably in the range of 0.001 to 0.1 (w / v)%, more preferably 0.01 to 0.05 (w / v)%. If the concentration of the sequestering agent is less than 0.001 (w / v)%, the effect of removing the polyvalent metal ions becomes insufficient, and if it is more than 0.1 (w / v)%, it is more than necessary and sufficient. Because.

  In order to effectively remove protein stains adhering to the contact lens, the solution of the present invention can be mixed with a proteolytic enzyme or used as a diluted / mixed solution of the enzyme agent. Examples of the proteolytic enzymes used in the present invention include plant-derived proteases such as papain, bromelain, gradient, and ficin, animal-derived proteases such as trypsin, chymotrypsin, and pancreatin, and bacterial proteases produced by bacteria such as Bacillus. Any of the microorganism-derived proteases can be used. Specifically, “Biolase” (manufactured by Nagase ChemteX Corporation), “Alcalase”, “Esperase”, “Sabinase”, “Durazyme”, “Subtilisin A” (manufactured by Novozymes Japan), “Protease” N “Amano”, “Protease S“ Amano ”” (manufactured by Amano Pharmaceutical Co., Ltd.), “Biosoak” (manufactured by Daiwa Kasei Co., Ltd.), and the like. The concentration of the proteolytic enzyme when blended from the beginning as a liquid is appropriately determined according to the cleaning effect to be obtained and the usage time, but if it is too small, the cleaning effect will not be sufficient, and it will be stabilized by the liquid preparation of the present invention. However, after a long period of storage, the enzyme activity decreases to some extent. Moreover, since the enzyme amount which acts on dirt is limited even if there is too much, 0.01-5 (w / v)% is suitable in the said liquid agent. And stabilization of the mix | blended proteolytic enzyme is achieved by the presence of the said C5-C6 polyol advantageously. In addition to dissolving the proteolytic enzyme and other compounding ingredients in a solvent such as purified water and providing it as a one-pack type as described above, a large number of proteolytic enzymes can be maintained in a more stable state. It is also possible to supply a two-component type with a liquid enzyme containing a large amount of a monohydric alcohol, and further supply a proteolytic enzyme in the form of a solid such as a tablet, granule or powder.

  In another preferred embodiment of the present invention, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,5-pentanediol, cyclopentane1,2-diol or 1 , 2-hexanediol, 1,3-hexanediol, 1,4-hexanediol, 1,5-hexanediol, 1,6-hexanediol, 2-methyl-2,4-pentanediol, cyclohexane-1,3 1 selected from the group of polyols having 5 to 6 carbon atoms consisting of diol, 1,2,6-hexanetriol, methylcyclohexane-1,2,4-triol, cyclohexane-1,2,4,5-tetrol A contact lens solution containing at least a seed and an effective amount of a proteolytic enzyme for cleaning the contact lens A. As described above, a specific polyol was blended and used mainly for the purpose of exerting a disinfecting effect in combination with a surfactant. However, the same polyol has an enzyme activity in combination with a proteolytic enzyme. It can be used as a component to maintain. Conventionally, it is known that polyhydric alcohols contribute to the stabilization of proteolytic enzymes, but there is no literature suggesting that the polyol is particularly preferable, and glycerin or propylene glycol is mainly used, and the specific The polyol is only exemplified. These specific polyols have been found to be excellent not only in enzyme stability but also in terms of safety and disinfection effects, and 1,2 hexanediol is particularly preferred. In such an embodiment, not only the specific polyol is used for enzyme stabilization, but also the antiseptic and disinfecting effects of the liquid agent are exhibited. It is preferable to mix boric acid or a salt thereof with this solution.

  When the proteolytic enzyme-containing liquid agent of the above embodiment is diluted to another appropriate contact lens liquid agent and prepared at the time of use (two-liquid mixed type), it flows as a concentrated liquid with a high proteolytic enzyme concentration, so the total volume It is convenient in terms of transportation, storage, and carrying by storing in a small container. In this case, the concentration of the specific polyol used is preferably 20 to 90 (w / v)%, more preferably 40 to 80 (w / v)%. When the concentration is lower than 20 (w / v)%, the enzyme concentration is relatively high, so the degradation of the enzymes progresses and the enzyme activity decreases due to storage. It tends not to be obtained, and even if it exceeds 90 (w / v)%, it does not contribute to the stabilization of the enzyme, and the osmotic pressure of the contact lens solution prepared by dilution at the time of use becomes too high. There is a risk of stagnation when the lens after treatment is worn. Here, in addition to the specific polyol, it is also possible to use a combination of other general polyhydric alcohols within the above-mentioned concentration range, and the specific polyol concentration in that case is 0.1 to the total amount. It can be made into the range of 15 (w / v)%. Boric acid or a salt thereof is preferably in the range of 0.001 to 10 (w / v)%, more preferably in the range of 0.1 to 10 (w / v)%. Although these boric acids have a large effect in contributing to enzyme stabilization, they are highly cytotoxic and may cause side effects such as hypersensitivity and inflammation when absorbed by the living body (JP 14 revision manual). Since it is not preferable to require a large amount, it is desirable to use in such a concentration range.

  On the other hand, when the proteolytic enzyme is mixed and distributed from the beginning and used as it is (one-pack type), the specific polyol is used at a low concentration. The polyol concentration in that case is in the range of 0.1 to 15 (w / v)%, preferably in the range of 0.5 to 5 (w / v)%. In the case of the one-pack type, the enzyme-containing solution is used without diluting, so if the polyol concentration is high, the osmotic pressure will be too high, which may affect the contact lens material and cause high eye irritation and damage to the eyes. For this reason, use in the above concentration range is desired. Boric acid or a salt thereof is used in the range of 0.001 to 10 (w / v)%, preferably in the range of 0.1 to 10 (w / v)%, for the same reason as described above.

  The two types of liquid agents (two-component mixed type and one-component type) each have the following characteristics, and can be used properly according to the purpose of use. In other words, in the case of the two-component mixed type, the enzyme solution is concentrated, so depending on the degree of contamination, use it daily for patients who are prone to get dirty, and once for patients who are not easy to get dirty. The frequency of use can be individually adjusted, such as weekly use. Enzyme solutions can be used for other types of contact lens solutions (including liquids containing surfactants and specific polyols that are one embodiment of the present invention, It has the advantage that it can be used in combination with a contact lens storage solution, a cleaning solution, etc., which is used, and in the case of a one-component type, there is a trouble that the enzyme solution must be diluted 10 to 200 times each time it is used. There is an advantage that the lens can be always washed with a constant amount of time without forgetting the treatment with the enzyme and without the dirt sticking to the lens after long-term use.

  Among the specific polyols, 1,2-hexanediol having one hydroxyl group at each of the terminal carbon of hexane and the adjacent carbon is glycerin or propylene glycol generally used in conventional contact lens solutions. In comparison, it can be suitably used as a contact lens solution as a substance having an excellent disinfection effect than glycerin, a higher safety than propylene glycol, and a substance having an excellent stabilizing effect on proteolytic enzymes. This use concentration is used in the above-described concentration range.

  By the way, generally various buffering agents are conventionally used for the liquid agent for contact lenses, in order to maintain stable pH. Also in the present invention, a buffering agent is used for the purpose of preventing a pH change from being produced until used or in contact with the outside air within the period of use. Specifically, borate buffer, phosphate buffer, Tris buffer, citrate buffer and the like can be mentioned, and among them, effective when used in combination with borate buffer and phosphate buffer. Since the disinfection effect is acquired, it is especially preferable. The concentration of such a buffer is generally 0.05 to 3.0 (w / v)%, preferably 0.1 to 1.5 (w / v)%, particularly preferably 0.3 to 1. 0.0 (w / v)%. This is because when the concentration of the buffer is lower than 0.05 (w / v)%, it is difficult to keep the pH of the contact lens solution constant, and from 3.0 (w / v)%. This is because even if it is high, the stability of the pH cannot be further improved. The pH of the liquid is preferably close to that of tears, and therefore is preferably in the range of 5-9. This pH is easily maintained by the buffering agent, and can maintain a stable quality throughout the storage and use period.

  Furthermore, in the contact lens solution according to the present invention, a thickener, an isotonic agent, and the like can be added as other additive components. Thickeners used to adjust the viscosity of the liquid agent include polyvinyl alcohol, poly-N-vinyl pyrrolidone, polyethylene glycol, polyacrylamide and hydrolysates thereof, polyacrylic acid, polyacrylate, isobutylene-maleic anhydride Acid copolymer, methyl vinyl ether-maleic anhydride copolymer, ring-opened product of each copolymer and its salt, hydroxyethyl cellulose, carboxymethyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, methyl cellulose, gelatin, sodium alginate And viscous bases such as sodium chondroitin sulfate, xanthan gum, gum arabic and girl gum. In order to relieve irritation to the eyes, it is desirable to use an isotonic agent. In that case, generally, an osmotic pressure of about 150 to 650 mOsm, and preferably about 200 to 350 mOsm when used for a liquid agent for soft contact lenses. Adjusted to As such an isotonic agent, sodium chloride, potassium chloride, sodium carbonate and the like can be used.

  In preparing the contact lens solution according to the present invention, as in the case of preparing an ordinary aqueous solution, it is easy to add each component to a predetermined amount of sterile purified water or deionized water and then dissolve it uniformly. Is obtained. The contact lens solution thus obtained is clear, and can be sterilized or aseptically filtered by an autoclave, if necessary. Further, the predetermined component may be supplied as a tablet or powder / granule and prepared by mixing and dissolving purified water or the like in a quantitative container by the user.

  The contact lens care method using the thus obtained contact lens solution according to the present invention is performed as follows. First, a few drops of the contact lens solution according to the present invention are dropped on the contact lens removed from the eye, and the contact lens is held between the thumb and forefinger or on the palm of the hand for several seconds to several tens of seconds. Rub. Next, after rinsing with such a liquid for contact lens, storage and disinfection are performed by immersing in a case filled with the liquid for 10 minutes to 24 hours, preferably 30 minutes to 8 hours. However, this is only an example, and the care method using the liquid agent of the present invention is not limited to the above. For example, when proteolytic enzymes are used in combination, if the contact lenses after storage are rinsed with tap water etc. and then worn again, or if the contact lenses are very dirty, use a cleaning agent that contains a special oxidizing agent. After processing, the usage method according to need, such as storing in the liquid preparation of the present invention, is adopted.

  Through the above series of treatments, the contact lens can be effectively and easily cleaned and disinfected, and it has a disinfecting effect without using a conventional disinfectant. Is advantageously resolved.

  In order to clarify the present invention more specifically, several examples of the contact lens solution according to the present invention are shown below. In addition, each component shown to a table | surface is shown by (w / v)%.

(Example 1 and Comparative Example 1)
-Disinfection effect test-
Serratia marcescens (S.m .: Serratia marcescens ATCC 13880), Pseudomonas aeruginosa (Pa .: Pseudomonas aeruginosa ATCC 9027), Staphylococcus aureus (Sa. Using each of those cultured on an SCD agar medium at 33 ° C. for 24 hours, suspended in a sterilized darbecolic acid buffer (hereinafter referred to as DPBST) to give a test bacterial solution of 10 ⁷ to 10 ⁸ cfu / ml It was prepared as follows.

  On the other hand, the inventive solution No. 1-6 and Comparative Example Solution Nos. Various contact lens solutions 1 or 2 were prepared in the composition shown in Table 1 below, and the pH was adjusted. It should be noted that sodium α-olefin sulfonate (trade name “OS-14” manufactured by Nikko Chemicals Co., Ltd.) is used as an anionic surfactant, and 1,2-pentanediol (trade name “Hydrolite-5”: ( (Trade name “KMO-6”: manufactured by Kosei Co., Ltd.). In addition, as a sequestering agent, disodium ethylenediaminetetraacetate (trade name “Clewat N” manufactured by Nagase ChemteX Corp.), boric acid buffer, isotonic agent (NaCl), nonionic surfactant polyoxy Ethylene cetyl ether (40) (trade name “BC40TX”: Nikko Chemicals Co., Ltd.) and amphoteric surfactant sodium laurylaminopropionate (trade name “Delift 151C”: Cognis Japan Co., Ltd.) were added. did. 10 ml of the prepared various contact lens solutions were taken in separate sterilized test tubes, and 0.05 ml of various test bacteria solutions were added thereto. After that, these various test liquid mixture liquids are stored in a constant temperature bath at 23 ° C., and 4 hours after the preparation of the liquid mixture, a certain amount of each liquid mixture is taken out, and each liquid mixture is sterilized. After dilution with finished DPBST, the viable cell count was determined by the agar plate pour method. The culture in this agar plate pour method was performed using a SCDLP agar medium at 33 ° C. for 5 days.

According to the above method, the number of viable bacteria immediately after inoculation and the number of viable bacteria after 4 hours from the preparation of the mixed solution are obtained, and the number of viable bacteria obtained by such measurement is logarithmized according to the following formula. The amount of reduced bacteria was calculated.
Bacterial decrease amount [logarithmic conversion] = LOG (viable cell count in 1 ml of bacterial suspension immediately after preparation) −LOG (viable cell count in 1 ml of bacterial suspension after treatment)
The results are shown in Table 1.

  From the results in Table 1, the solution No. according to the present invention was obtained. When the contact lens solution according to 1 to 6 is used, the comparative solution No. It turns out that there exists a high disinfection effect compared with the case where the polyol shown by 1 is not used. Comparative liquid No. When the glycerin shown by 2 was used, the disinfection effect was hardly recognized.

(Example 2 and Comparative Example 2)
-Antiseptic effect test-
Aspergillus niger (An: Aspergillus niger) as a test bacterium, cultured in SGA medium (Sabouraud glucose agar medium) at 23 ° C. for 7 days, 0.05% polysorbate-added sterile physiology It was suspended in a saline solution and prepared to be a test bacterial solution of 10 ⁷ to 10 ⁸ cfu / ml. In addition, S.M. a. And P.M. a. Was prepared in the same manner as in Example 1 except that the suspension was sterilized physiological saline (hereinafter referred to as saline). In the disinfection effect test described in Example 1, the same operation as described above was performed except that the sample collection time (4 hours) from the mixed solution was 2 weeks or 4 weeks later, and the dilution was saline. . 4 and Comparative Solution No. 2 was used to evaluate the antiseptic effect. In addition, A. n. The culture conditions in the agar plate pour method are about 23 ° C. × 7 days using GPLP agar medium. The results are shown in Table 2.

  From the results shown in Table 2, when the contact lens solution according to the present invention was used, the comparative solution No. It can be seen that there is a high antiseptic effect compared to the case where the polyol shown in 2 is not used.

(Example 3, Comparative Example 3 and Comparative Reference Example)
-Disinfection effect: Comparison with other disinfectants-
In the component composition shown in Table 3, a liquid preparation for contact lenses was prepared (Liquid No. 7), and the test was conducted on the case where other bactericides were used in combination with an anionic surfactant. In addition, as a nonionic surfactant, polyoxyethylene alkylphenyl ether (trade name “Nonion HS-220”: manufactured by NOF Corporation) is generally used for disinfecting contact lenses (particularly soft contact lenses). Polyhexamethylene biguanide (trade name: Cosmocil CQ, manufactured by Avicia Co., Ltd.) as the cationic fungicide used, and dioctylaminoglycine hydrochloride (trade name: Sarabon, manufactured by Takemoto Yushi Co., Ltd.) as the amphoteric fungicide Was used. Table 3 shows the results of the same disinfection effect test as in Example 1.

  From the results in Table 3, the comparative solution No. The general bactericides used in 3 to 4 show an excellent disinfecting effect in a liquid in which an anionic surfactant is not present (Comparative Reference Examples 1 and 2), but are remarkably effective due to the presence of the anionic surfactant. Can be seen to be reduced. In addition, although it seems that the polyol concentration in the present invention example is used higher than the general disinfectant of the comparative example, the disinfectant concentration is derived from the effect and safety, For example, if the above general disinfectant is used in the presence of an anionic surfactant in the amount used, such as the polyol of the present invention example, it may have some disinfecting effect. When used at a concentration, there is a problem in safety, so the above concentration setting is used.

Example 4
-Cleaning effect test-
Invention Example Solution Nos. With respect to the contact lens solutions 1 to 6, a cleaning effect test was performed as follows. First, sorbitan monooleate: 6 w / v%, castor oil: 16 w / v%, lanolin: 35 w / v%, oleic acid: 5 w / v%, sorbitan trioleate for use in the cleaning effect test : 4 w / v%, cetyl alcohol: 2 w / v%, cholesterol: 2 w / v%, and cholesterol acetate: 30 w / v%, and 2.5 parts of artificial lipid solution homogenized by stirring, and physiological saline An artificial lipid solution was prepared by mixing 97.5 parts of water.

  An oxygen-permeable hard contact lens (trade name “Menicon Super EX”: manufactured by Menicon Co., Ltd.) is prepared as a test lens, and 5 μL of the artificial lipid solution is uniformly adhered to both surfaces of the artificial lipid solution on the surface thereof. A lens with lipid soil adhesion was obtained. Then, the obtained artificial lipid dirt adhesion lens is taken in the palm of the palm, and the solution No. 2 to 3 drops of the contact lens solution 1 to 6 were dropped, and the contact lens was cleaned by rubbing with a fingertip for 5 seconds.

  After the cleaning treatment, the appearance of the contact lens was observed. As a result, the artificial dirt adhering to the contact lens was completely removed regardless of which solution of the present invention was used. As is clear from this result, the contact lens solution according to the present invention has an excellent cleaning effect in addition to its excellent disinfecting effect.

(Example 5)
-Protein removal effect test-
Invention Example Solution Nos. With respect to the contact lens solutions 1 to 6, a protein removal effect test of a solution obtained by mixing a liquid enzyme with this was performed as follows. First, for use in the protein removal effect test, bovine albumin: 0.388 (w / v)%, bovine γ-globulin: 0.161 (w / v)%, egg white lysozyme: 0.12 (w / V)%, sodium chloride: 0.9 (w / v)%, calcium chloride dihydrate: 0.015 (w / v)%, sodium dihydrogen phosphate dihydrate: 0.104 (w / V)% was dissolved in water, and an artificial tear was adjusted to pH 7.0 using 1N sodium hydroxide.

  The test hard contact lens was prepared, heat-treated at 80 ° C. for 30 minutes while the contact lens was immersed in 10 ml of the artificial tears, and then washed with tap water. After repeating this operation five times, it was confirmed that the lens surface was completely clouded, and these artificial cloudy lenses were used as test lenses and used in the following experiments. In addition, when the created white turbidity lens was subjected to image analysis by the method described later and the degree of white turbidity was determined, all the white turbidity obtained was 255.

-Image analysis method-
A CCD camera XC-77 (manufactured by Sony Corporation) inputs the processed lens as a monochrome image, and then performs A / D conversion with IMAGE ANALYZER V2 (manufactured by Toyobo Co., Ltd.), and the image is vertically and horizontally Decompose into 512 pixels. Each density is converted into a digital image divided into 256-level luminance, and the density values are converted so that the histogram heights are the same for all the density values.

  The liquid agent containing the enzyme is 2.0 (w / w)% of proteolytic enzyme (trade name: Bioplase: manufactured by Nagase ChemteX Corp.), 10.0 (w / w)% of borax, and 60 of glycerin. 0.0 (w / w)% and water 38.0 (w / w)% mixed and prepared, and 0.3 mL was added to 10 mL of the contact lens solution. The artificial white turbid lens is immersed in this mixed solution and stored at room temperature for 4 hours, and then the lens is taken out, washed with tap water, dried, and the degree of white turbidity stain remaining on the lens is determined by the above method. Obtained by image analysis. As a result, the obtained turbidity was 10 to 22, indicating that the cleaning effect was very good. In addition, the white turbidity of the untreated lens before adhesion of dirt was 2 to 8.

(Example 6)
-Enzyme stability test 1-
Invention Example Solution No. 4 and Comparative Solution No. The contact enzyme solution was mixed with 0.12% of the above contact lens solution, and the enzyme activity of the solution was measured according to the following method, while stored at 25 ° C for 6 months, or at 35 ° C. Each enzyme activity was measured in the same manner after 6 months of storage, and the residual enzyme activity was calculated according to the following formula.

-Activity measurement of proteolytic enzyme (TNBS method)-
Add 0.9 ml of 1% sodium sulfite solution to 0.6 ml of each solution (sample) and leave at 50 ° C. for about 2 minutes. Thereafter, 0.4% DMC substrate solution (20 ml of purified water was put in a vial, heated to 80-100 ° C. with a hot plate, 0.20 g of dimethyl casein (manufactured by Novozymes Japan) was added, and 20 minutes. Stir with a stirrer and dissolve completely.After dissolution, add 20 ml of borate buffer solution (4.28 g of borax and 4.15 g of sodium dihydrogen phosphate dihydrate dissolved in 100 ml of purified water), Further, 0.6 ml of a solution made up to a total volume of 50 ml with purified water) was added, and after 1 minute at 50 ° C., 0.15 ml of a 0.1% sodium 2,4,6-trinitrobenzenesulfonate (TNBS) solution was added, and further 50 ° C. Put on for 25 minutes. After the reaction, add 1.5 ml of cold water, leave at room temperature for 25 minutes, and measure the absorbance at a wavelength of 425 nm (as a control, use 0.6 ml of 1% sodium sulfite solution instead of the sample). . A solution having a known enzyme concentration is measured in advance by the same method as described above to prepare a calibration curve, and the enzyme concentration of the sample is determined from the absorbance of the measurement result.
Residual enzyme activity (%) = (Proteolytic enzyme activity after storage / Proteolytic enzyme activity at the time of preparation) × 100

  Invention Example Solution No. For the liquid formulation No. 4, the residual activity of the enzyme stored at 25 ° C. for 6 months was 100%, while the residual activity of the enzyme stored at 35 ° C. for 6 months was 85%. For the solution of No. 1, the residual activity of the enzyme stored at 25 ° C. for 6 months was 40%, and the residual activity of the enzyme stored at 35 ° C. for 6 months was 0%. From this result, it can be seen that the liquid preparation of the present invention can be stored and used for a long period of time while maintaining a high enzyme activity.

(Example 7)
-Enzyme stability test 2-
As shown in Table 4, Example Solution No. 8-9 and Comparative Solution No. 5-6 were prepared and the stability test was implemented by the method similar to Example 5. FIG. The results are also shown in Table 4.

  From the results shown in the table, it can be seen that the specific polyol of the present invention is superior in proteolytic enzyme stability even at a low concentration as compared with other polyols.

(Example 8)
Invention Example Solution No. Regarding the contact lens solution of No. 4, the effect on the contact lens was confirmed by the following test.
-Lens compatibility test-
Invention Example Solution No. In Example 4, the enzyme was mixed to 0.12% in the same manner as in Example 5, and one piece of oxygen-permeable hard contact lens (trade name “Menicon Z” manufactured by Menicon Co., Ltd.) was immersed in 2 ml of the mixed solution. After storage for 1 month at 25 ° C (however, the liquid was changed every day), the appearance of the lens (n = 3), specifications (base curve, power, size), light transmittance, surface wettability, contact angle Was measured and compared with the lens before the test. As a control, a commercially available contact lens cleaning stock solution (trade name “O-to-care milfa” manufactured by Menicon Co., Ltd.) was used. As a result, there was no difference between the example of the present invention and the control in terms of appearance, standard, and light transmittance with respect to the lens before the test. The water wettability was slightly improved in both the inventive example and the control as compared to before the test, and the evaluation by contact angle was 47 ° before the test, 39 ° in the inventive example, and 50 ° in the control. Yes, it was judged that the efficacy was equivalent or better than that of the control. Therefore, it can be seen that the liquid preparation of the present invention example is not an object that adversely affects the lens but has good compatibility.

Example 9
Invention Example Solution No. The safety of the contact lens solution 4 was confirmed by the following test.
-Treated lens extract rabbit eye drop test-
(Preparation of test solution) Solution No. 1 ml of oxygen permeable hard contact lens (trade name “Menicon EX”: manufactured by Menicon Co., Ltd.) was immersed in 2 ml of the liquid 4 for 8 to 12 hours and then taken out, and the liquid was dropped onto the 2 to 3 drop lens. The cycle of rubbed with a fingertip for 5 seconds, rinsed with tap water for 5 seconds, and dipped again in 2 ml of a new solution was repeated 30 times. Twenty lenses having the same treatment are prepared, and ten of them are put into a 10 ml vial, and 2 ml of physiological saline is added to one and 2 ml of sesame oil is added to the other. Extraction from the lens is performed at 37 ± 1 ° C. for 72 hours, and the external solution is taken out and used in the eye drop test within 24 hours. As a control, a contact lens cleaning storage solution (trade name “O-to-care”: manufactured by Menicon Co., Ltd.), which has been treated in the same manner and extracted, was used as a control.
(Instillation test) 0.1 ml of physiological saline extraction test solution was instilled into one eye of the eyelid, and 0.1 ml of physiological saline extraction control solution was instilled into the other eye, and the eyes were closed for 30 seconds, and then immediate irritation was observed. This instillation was performed on a total of 3 pupae, and after 1, 24, 48, and 72 hours after the instillation, the state of the anterior segment was observed with the naked eye and a slit lamp, and according to the evaluation method of Draize, The findings were recorded. For the sesame oil extract, the same test was conducted on three pupae.

  As a result of the test, there is no difference between the inventive example and the control, and those extracted with physiological saline or sesame oil show no immediate irritation, and the evaluation by the Draize method is “non-irritant”. It was judged. Therefore, it was proved that the safety of this solution was high.

  INDUSTRIAL APPLICABILITY The present invention can provide a contact lens solution that can exhibit a sufficient antiseptic or disinfecting effect even under the coexistence of various compositions and contains a bactericide that is highly safe for the eyes. . In addition, when a proteolytic enzyme is added to the solution as a multipurpose contact lens solution, a solution that enables long-term maintenance of the enzyme activity can be provided.

Claims (5)

0.1-5.0 (w / v)% 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,5-pentanediol, cyclopentane1,2-diol or 1,2-hexanediol, 1,3-hexanediol, 1,4-hexanediol, 1,5-hexanediol, 1,6-hexanediol, 2-methyl-2,4-pentanediol, cyclohexane-1, Selected from the group of C5-C6 polyols consisting of 3-diol, 1,2,6-hexanetriol, methylcyclohexane-1,2,4-triol, cyclohexane-1,2,4,5-tetrol With one or more,
A contact lens solution containing 0.01 to 3.0 (w / v)% of an anionic surfactant.     The contact lens solution according to claim 1, further comprising a sequestering agent.     A liquid enzyme agent comprising an effective amount of a proteolytic enzyme for washing a contact lens and 20 to 90 (w / v)% polyhydric alcohol with respect to the contact lens solution according to claim 1 or 2 The contact lens cleaning liquid, which is prepared by diluting 10 to 200 times. 0.5-5 (w / v)% 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,5-pentanediol, cyclopentane1,2-diol or 1, 2-hexanediol, 1,3-hexanediol, 1,4-hexanediol, 1,5-hexanediol, 1,6-hexanediol, 2-methyl-2,4-pentanediol, cyclohexane-1,3- One selected from the group consisting of diol, 1,2,6-hexanetriol, methylcyclohexane-1,2,4-triol, cyclohexane-1,2,4,5-tetrol and a polyol having 5 to 6 carbon atoms With the above,
A contact lens solution comprising an effective amount of a proteolytic enzyme for cleaning contact lenses. 5. The contact lens solution according to claim 4, further comprising boric acid or a salt thereof.