JP4533110B2 - Ophthalmic solution - Google Patents

Description

  The present invention relates to an ophthalmic solution having an antibacterial effect and an antiseptic effect, and more particularly to a cleaning and preserving agent that is effective and safe for cleaning and storing contact lenses in order to maintain a comfortable wearing of a contact lens user.

  Since ophthalmic solutions are used in small portions over a long period of time, a preservative (antibacterial agent) is generally added to maintain sterility during storage. Examples of such ophthalmic solutions include paraoxybenzoic acid esters (JP-B-7-5456, etc.), benzyl alcohol, chlorobutanol, benzalkonium chloride, benzethonium chloride, sorbic acid, and the like. Polyhexamethylene biguanide and polyquaterium are used as a storage solution for lenses. These antibacterial agents are appropriately selected from the viewpoints of antibacterial spectrum, action time, allergy and insensitivity, and are blended at an appropriate concentration.

  Although p-hydroxybenzoate is much less toxic than salicylic acid and benzoic acid, it has a narrow antibacterial spectrum and may cause contact dermatitis and allergic eczema in some people. Chlorobutanol has strong antibacterial activity. These effects can be a major cause of corneal injury when the eye drops containing the substance are frequently instilled or applied to patients with dry eye symptoms. Further, although benzalkonium chloride and benzethonium chloride have a high antiseptic effect, they may cause corneal damage when the concentration is high, and the use concentration is accompanied by certain restrictions. In addition, these antibacterial agents may cause an interaction with additives and are easily adsorbed on a filtration filter or an eye drop container. In particular, benzalkonium chloride is most frequently used in ophthalmic solutions, and many studies on ocular toxicity have been reported on cultured cells, experimental animals, human corneas, and the like. Among them, Takahashi et al. (Japanese ophthalmology 58: 945-950, 1987) reported that cell damage appeared even when the concentration was lower than ½ of the concentration normally used for ophthalmic solutions, even when the concentration was frequently applied. It is reported that it is possible.

  On the other hand, when used for cleaning and storing a contact lens, there is a concern about the adsorption of the lens material itself. Especially when used in contact lenses, the problem is that the antibacterial agent stays in the lacrimal fluid for a long period of time due to adsorption to the lens and when the lens is worn on the eye, as the antibacterial agent is released from the lens material. Therefore, the risk of inducing corneal cell damage is extremely high compared to the case of temporary contact such as eye drops. In recent years, gas permeable hard contact lenses made of silicone acrylate and fluorosilicone acrylate materials have been tested for the possibility of incorporating the above-mentioned antibacterial agents, and the amount of incorporation is proportional to the ambient temperature and the concentration in the liquid agent. There is a report that the risk increases with the long-term storage of contact lenses in the summer (Nippon Kore, Vol. 34: 267-276, 1992). There is also a method of adding a formaldehyde donor such as bronopol as an antibacterial agent other than the above because the effect of the antibacterial agent is inhibited by reaction with other components added to the contact lens solution. Is a compound that is regarded as a social problem as a causative agent of sick house syndrome, and there is resistance to using it.

  Furthermore, the water-containing soft contact lens absorbs water, and the polymer chain constituting the lens material is elongated to increase the gap between the polymer chains. Examples of using a high molecular weight agent include polyhexamethylene biguanide (see Japanese Patent Publication No. 6-49642) and polyquaterium (see Japanese Patent Publication No. 2-54804). However, since these antibacterial agents are all cationic in a solution, there is a problem that when used in the presence of an anionic surfactant, the antibacterial activity is lowered and the antibacterial property cannot be expected substantially.

  The above-mentioned problem is not a perfect one that completely satisfies both sides of the antiseptic effect and safety as an antibacterial agent. In short, the optimal antibacterial agent in each case according to the purpose of use, use state, use mode, etc. This has been dealt with by selecting. And this disinfection effect and safety are of mutually contradictory (front and back) nature, that is, if you try to increase the disinfection effect, the effect on the human body will inevitably increase, while safety Since the disinfection effect tends to be low if emphasis is placed on, the development of new antibacterial agents is awaited in the future.

Japanese Examined Patent Publication No. 2-54804 Japanese Patent Publication No. 6-49642 Japanese Patent Publication No. 7-5456 U.S. Pat. No. 3,833,731 JP-A-9-165306

  An object of the present invention is to provide a new ophthalmic solution for antibacterial and / or antiseptic purposes, and particularly to provide a solution having excellent safety and antibacterial and antiseptic effects when used in contact lenses. There is.

  And in the present invention, as a result of intensive studies to solve the above problems, it has been found that antibacterial agents that have not been used in the ophthalmic field so far can be effectively used in the field, The invention was completed. Specifically, the present invention provides an ophthalmic solution containing 1,2-dibromo-2,4-dicyanobutane which has been used as a preservative and preservative for sunscreens, hair care products, cosmetics and the like. Moreover, as a preferable embodiment of the present invention, the compounding amount of the above components is contained at a concentration of 0.15 to 0.00005 w / v%.

  The ophthalmic solution according to the present invention is particularly useful as a contact lens solution, and 1,2-dibromo-2,4-dicyanobutane has an excellent antiseptic action without causing interaction with other coexisting components, It exhibits a bactericidal action, does not cause adsorption and accumulation on the lens, and is excellent in safety because the antibacterial agent itself has extremely low toxicity.

  Furthermore, a surfactant, a buffer, a tonicity agent, a thickener, a chelating agent, and the like can be appropriately added to the ophthalmic solution according to the present invention depending on the application. This is because these additions can provide various functions necessary for an ophthalmic solution, preferably a contact lens solution.

  By blending the antibacterial agent according to the present invention, the antiseptic and bactericidal effects of the ophthalmic liquid agent are improved, and the antibacterial agent itself has low toxicity, so that a liquid agent having sufficient safety for the eyes can be provided. Especially when used as a liquid for contact lenses, there is no interaction with other coexisting components, stable antiseptic and bactericidal effects can be maintained, and antibacterial agents do not absorb or accumulate on contact lenses. It is possible to provide a treatment solution for realizing comfortable wearing of contact lenses.

Hereinafter, the present invention will be described in more detail.
1,2-Dibromo-2,4-dicyanobutane (hereinafter abbreviated as DBDCB) is known as an antibacterial agent together with related compounds (US Pat. No. 3,833,731). However, there is no description in the publication that it can be used as an ophthalmic solution or as an antiseptic or bactericidal agent for a contact lens solution. Although the above-mentioned U.S. Patent Document shows that it is used as a disinfectant for paper, leather, fiber, resin, paint, wood, tobacco, oil, rubber, resin film, etc., it is a field targeted by the present invention. No suggestion has been made regarding its use in the field. DBDCB is currently added as a preservative to products such as cosmetics and shampoos and conditioners, and since it is slightly soluble in water, its solubility has been improved by using dipropylene glycol as a solvent. "1190" and supplied by Nalco, USA.

  In the present invention, by using DBDCB as an antiseptic / antibacterial agent for ophthalmic solutions, it is possible to maintain the solution in a sterile state for a long period of time. In particular, when used in a contact lens solution, a bactericidal effect is effectively exhibited in a state where there is no possibility of causing a side reaction with other components coexisting in the solution. DBDCB has a bromine and a nitrile group in its structure, and a good antiseptic and bactericidal effect is exhibited by these actions. The bactericidal action mechanism is not necessarily clear, but it is said to be due to destruction of a part (protoplasm) including the nucleus and cytoplasm in the cell.

  And the amount of addition when using the DBDCB as a bactericidal component varies depending on the combined use with other bactericidal components, the use and purpose of the ophthalmic solution, and other components to be added. When used for the purpose of washing and storage, it is specifically used in a concentration range of 0.15-0.00005 w / v%, preferably 0.05-0.0001 w / v%. Is done. Referring to toxicity data (provided by CALGON, USA) that causes moderate irritation to the conjunctiva even though there is no effect on the rabbit eye cornea with a solution of 0.2 w / v% or more, the concentration is 0.15 w If it is higher than / v%, it is more than necessary for the development of antiseptic and sterilizing effects, and there may be a problem in safety. Further, when the concentration is lower than 0.00005 w / v%, there is a possibility that sufficient antiseptic / sterilizing effects may not be exhibited.

  In the present invention, other bactericidal components that can be used in combination with DBDCB include paraoxybenzoic acid esters, benzyl alcohol, chlorobutanol, benzalkonium chloride, benzethonium chloride, sorbic acid, which have been conventionally used in the field of ophthalmic solutions. Examples include polyhexamethylene biguanide and polyquaterium. By using these components in combination with DBDCB, each component will have a broader antibacterial spectrum than that used alone, and each component is expected to exhibit a higher bactericidal effect at lower concentrations. .

As the contact lens solution in the present invention, a surfactant is added for the purpose of imparting a cleaning effect to the solution in order to remove dirt such as proteins and lipids derived from tears and the like adhering during wearing of the contact lens. As such surfactants, any conventionally known surfactants can be used as long as they are highly safe to the living body and do not affect the contact lens material. Anionic surfactants and nonionic surfactants can be used. Any of these agents, cationic surfactants, amphoteric surfactants, or a combination thereof may be used. In particular, when cleaning hard contact lenses, it is preferable to add an anionic surfactant that has a high cleaning effect on lipids, because dirt such as eye grease is likely to adhere to the lens material. In addition, by using a specific anionic surfactant and a nonionic surfactant in combination, even if it is immersed for a short time, it has a remarkable detergency and maintains the hydrophilicity of the lens surface. The prior art (Japanese Patent Publication No. 1-31602) disclosed about a certain liquid agent is employable also in this invention.
In the case of hard contact lenses, the active agent added to the liquid agent is not brought directly into the eye because it is used after being rinsed with tap water after washing with the liquid agent. Then, since a system in which cleaning and disinfection is performed with a single solution and is used as it is after the treatment becomes common and the solution needs to be a solution that does not irritate the eyes, it is preferable to use a nonionic surfactant.

  Examples of the anionic surfactant include α-olefin sulfonate, alkyl sulfonate, alkyl benzene sulfonate, carboxylated ether salt having a polyoxyethylene chain, alkyl phosphate, and polyoxyethylene chain. And alkyl ether phosphate / sulfate, alkyl sulfate ether, N-acyl taurine salt, N-acyl amino acid salt, alkyl ether carboxylate and the like. Nonionic surfactants include polyoxyethylene polyoxypropylene block polymers, polyoxyethylene polyoxypropylene-substituted ethylenediamines, polyoxyethylene glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, poly Oxyethylene 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 alkyl phenyl ethers, polyoxyethylene alkyl ethers, polyoxy Chi Ren lanolin alcohols, and than can be exemplified polyoxyethylene fatty acid amides, among others, preferably those containing a polyoxyethylene chain structure is employed. As the cationic surfactant, a long-chain alkylamine acetate, a long-chain alkyltrimethylammonium chloride and the like can be used, and as an amphoteric surfactant, a glycine type such as alkylpolyaminoethylglycine, lauryldimethylaminoacetic acid betaine, And amphoteric surfactants such as betaine acetate type, imidazoline type, alkylaminopropionic acid, alkylaminopropionate and the like.

  The amount of the surfactant used varies depending on the surfactant used, but is generally in the range of 0.005 to 5.0 w / v%, more preferably 0.01 to 2.0 w / v%, Preferably, it is about 0.05 to 1.0 w / v%. This is because when the amount used is small, the resulting cleaning effect is insufficient, and when the amount used is too large, it may cause adsorption / accumulation on the contact lens material and eye irritation.

  Furthermore, the ophthalmic solution according to the present invention is conventionally used for ophthalmic solutions and contact lens solutions such as physiologically acceptable buffers, isotonic agents, thickeners, chelating agents, etc., if necessary. Known additives that have been selected can be appropriately selected and contained.

  For example, the buffer is used to maintain the pH of the solution at a predetermined value, prevent changes and denaturation of the content components, and prevent irritation to the eyes and skin. The neutrality is maintained in the range of 0.0 to 8.0, preferably around 7.0. Conventionally known buffers include borate buffer, phosphate buffer, citrate buffer, carbonate buffer, trishydroxymethylaminomethane buffer, tartrate buffer, various amino acid salt buffers, etc. Can be illustrated. These buffering agents are generally about 0.01 to 2 w / v%, but are blended so that the osmotic pressure of the solution does not become too high by adjustment with the use of an isotonic agent described later. Is done. In addition, although there is no effect | action as said buffering agent, in order to adjust the pH of the liquid agent after preparation only to neutral vicinity, it is also possible to add sodium hydroxide, hydrochloric acid, etc. In this case, the liquid is preferably such that the pH does not change later.

  Conventionally known isotonic agents can also be used. Specifically, there are sodium chloride, potassium chloride, sodium citrate, boric acid, borax, sodium carbonate, sodium phosphate, sodium sulfate, sorbitol, glucose, mannitol, trehalose, propylene glycol, ethylene glycol, glycerin, etc. You may use combining these. The use concentration of these isotonic agents is about 0.01 to 3 w / v%, and the osmotic pressure of the prepared liquid is set to 200 to 400 mOsm in a range substantially equal to physiological osmotic pressure. preferable.

  Further, a thickener can be optionally added. For example, maleic anhydride copolymers such as methyl vinyl ether-maleic anhydride copolymer, isobutylene-maleic anhydride copolymer, and ring-opening products thereof; polyvinyl Alcohol, polyvinylpyrrolidone, polyacrylamide, polyethylene glycol; cellulose derivatives such as hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, methylcellulose; dextran; sodium alginate; ophthalmic physiologically acceptable such as gum arabic and gum tragacanth Water-soluble polymers. These thickeners act as a cushion between the fingers and the lens when cleaning contact lenses, improve the feeling of cleaning, and improve the wettability of the lens surface during storage. Contribute. Among these examples, when the ophthalmic solution of the present invention is used for washing and storing hard contact lenses, maleic anhydride such as methyl vinyl ether-maleic anhydride copolymer, isobutylene-maleic anhydride copolymer, etc. Acid copolymers and these ring-opening products are preferred from the viewpoints of easy filtration after preparation of the liquid preparation, good tactile feel during washing, and imparting appropriate viscosity during use.

  The content of the thickener in the liquid agent varies depending on the type of the thickener to be added, and thus cannot be determined unconditionally, but is set so that the viscosity of the liquid agent (at 25 ° C.) is in the range of 1 to 30 cps. In addition, 0.01 to 10 w / v%, preferably 0.02 to 5 w / v% is desirable. If the content of the thickener is too small, the effect of adding the thickener (cushioning between the lens and fingers, etc.) cannot be achieved. If it is too large, the resulting liquid will be gelled and handled. This is because it becomes difficult.

  Furthermore, a chelating agent can be added to the liquid agent of the present invention. The chelating agent has a bacteriostatic effect to suppress the growth of microorganisms in the solution, and when used for contact lenses, divalent metal ions such as calcium ions present in tear fluid and proteins, etc. However, it also has an effect of preventing the formation of complex dirt on the lens. Various conventionally known chelating agents can be used, such as ethylenediaminetetraacetic acid (EDTA) and its sodium salt, citric acid and its salt, trishydroxymethylaminomethane, polyphosphoric acid, sodium hexametaphosphate, nitrilotriacetic acid and the like. It can be used, and it is used in the range of 0.01 to 5 w / v%. If the content is too small, there is no point in adding, and if it is too much, it is uneconomical.

  Anti-allergic agents such as allantoin and azulenesulfonic acid; anti-allergic agents such as chlorpheniramine maleate, diphenhydramine hydrochloride and sodium cromoglycate; and corneal protective agents such as hyaluronic acid and its salts. A decongestant such as naphazoline hydrochloride and naphazoline nitrate; a refreshing agent such as menthol, mint oil, mint water, camphor, borneol and bergamot oil; and the like can be added. These additives are used in a range that does not cause eye damage when applied to the eye and does not adversely affect the lens material when used for contact lenses.

  Hereinafter, in order to clarify the present invention more specifically, some examples will be illustrated focusing on the ophthalmic solution according to the present invention, especially the cleaning storage solution for contact lenses.

Each of the indicated preparations was evaluated by the following storage efficacy test.
-Preservation efficacy test (see Japanese Pharmacopoeia 14th revision)-
As a test bacterium, Staphylococcus aureus (Sa: Staphylococcus aureus ATCC 6538) or Candida albicans (Ca: Candida albicans ATCC 10231) was used. X 24 hours culture was suspended in physiological saline and prepared as a test bacterial solution of 10 ⁸ cfu / ml, while Candida albicans was cultured on Sabouraud glucose agar medium at 20 ° C. for 48 hours. The product was suspended in physiological saline and used as a test bacterial solution of 10 ⁸ cfu / ml.

Next, about the ophthalmic solution to be evaluated for storage effect, 10 ml is put into a sterilized test tube, and 0.05 ml of a predetermined one of the test bacterial solution prepared above is further added thereto, and then 25 ° C. And after a specified period of time (specifically, 7, 14, 21, 28), take out a certain amount, dilute with sterile saline, and pour The number of viable bacteria in 1 ml of the sample was measured by the plate method. The culture conditions in this pour plate method are as follows: for Staphylococcus aureus, culturing at 30 ° C. for 5 days using a soy bean casein medium; for Candida albicans, using a Sabouraud-glucose agar medium. And cultured at 25 ° C. for 5 days. And, after calculating the number of viable bacteria after the specified time of the liquid agent to which the test bacterial solution was added from the number of viable bacteria obtained by such measurement, the amount of bacterial reduction converted to logarithm according to the following formula Asked.
Bacterial reduction 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 period)
And when the result of the following Table 1 is obtained, it determines with having preservative effect.

Table 1

[Example 1]
Solution Nos. 1 to 10 and comparative solution No. 1 were prepared according to the blending amounts shown in Tables 2 and 3 (percentages in the table indicate w / v% concentration). Here, Margard 1190 (manufactured by Nalco, USA) used as a bactericidal component is obtained by dissolving DBDCB in dipropylene glycol at a concentration of 10 w / w%. Therefore, the net compounding amount of DBDCB is 1/10 of the notation.

 Next, the storage efficacy of each solution was examined according to the previous storage efficacy test, and the results are also shown in Tables 2 and 3. As is apparent from the results of this table, the storage efficacy of the liquid preparation according to the present invention passed the standards required by the Japanese Pharmacopoeia. On the other hand, the comparative solution containing no margard 1190 did not pass the storage efficacy test, and the effect of the bactericidal component Margard 1190 was proved. As a liquid formulation component, menthol (manufactured by Nippon Terpene) is a cooling agent, sodium tetradecenesulfonate (manufactured by Nikko Chemicals) is an anionic surfactant, POE (10) behenyl ether, POE (20) stearyl ether, POE (40) cetyl ether (manufactured by Nikko Chemicals), Lutrol F127 (polyoxyethylene polyoxypropylene block polymers; manufactured by BASF) are non-ionic surfactants, hydroxypropyl methylcellulose (manufactured by Shin-Etsu Chemical), alginic acid Sodium (manufactured by Kibun Food Chemifa), GANTREZ MS-955 (methyl vinyl ether-maleic anhydride copolymer; manufactured by ISP, USA) was added as a thickener. The intended ophthalmic solution That.

Table 2

Table 3

[Example 2]
Next, using the solution No. 3 described in Table 2 as a cleaning / disinfecting solution for hydrous soft contact lenses, the disinfecting effect of the solution was evaluated by the following test method.
-Disinfection effect test (see ISO 14729)-
Serratia marcescens (Sm: Serratia marcescens ATCC 13880) or Candida albicans (Ca: Candida albicans ATCC 10231) is used as a test bacterium. The suspension was suspended in darbecolic acid buffer (phosphate buffer containing sodium chloride, potassium chloride, polyoxyethylene sorbitan monooleate) and prepared as a test bacterial solution of 10 ⁸ cfu / ml, while Candida -About albicans, what was cultured at 20 degreeC x 48 hours on the Sabouraud glucose agar medium was suspended in the same buffer solution, and it was set as the test microbial solution of 10 < ⁸ > cfu / ml.

Next, about the ophthalmic solution to be evaluated for bactericidal effect, 10 ml is put into a sterilized test tube, and 0.05 ml of a predetermined one of the test bacterial solution prepared above is further added thereto, and then 25 ° C. In a constant temperature water bath, and after a specified time (specifically, 4 and 8 hours), take out a certain amount thereof, dilute with sterilized physiological saline, The number of viable bacteria in 1 ml of the sample was measured. The culture conditions in this pour plate method are SCDLP agar (Eiken Chemical) for Serratia marcescens, and GPLP agar (Wako Pure Chemical Industries) for Candida albicans. Each was cultured at 33 ° C. for 5 days. And, after calculating the number of viable bacteria after the specified time of the liquid agent to which the test bacterial solution was added from the number of viable bacteria obtained by such measurement, the amount of bacterial reduction converted to logarithm according to the following formula Asked.
Bacterial reduction 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 period)

Table 4

  As apparent from the results shown in Table 4, the soft contact lens cleaning / disinfecting solution according to the present invention showed an excellent disinfecting effect.

[Example 3]
The ophthalmic solutions No. 1, 4, 8, and 10 were evaluated by the following test methods for confirming the safety of the solutions.
-Growth inhibition test-
Mouse fibroblasts: The L-929 strain was diluted to 1 × 10 ⁵ cells / ml, then added to a 96-well, flat-bottom tissue culture plate at 100 microliters, and placed in a 37 ° C. CO ₂ incubator for 4 hours. Culture was performed. And after confirming that the cell had adhered to the bottom face, the said liquid agent was added 10 microliters and it culture | cultivated at 37 degreeC. Three days later, the medium in each well was removed and washed, and live cells were quantified as the protein mass (Lowry method), and the inhibition rate was determined from the ratio of the cells in the wells to which the test solution was not added to the protein mass.

  As a result of this growth inhibition test, the growth inhibition rate in these test solutions is 0%, and no inhibition of cell growth is observed. Therefore, the liquid preparation according to the present invention is considered to be highly safe. It is done.

[Example 4]
Regarding the safety of the contact lens solution of the present invention, the following test was conducted to confirm the adsorption to the lens material when the contact lens was immersed and stored.
-Adsorption to lens (Agar overlay test)-
In 2.0 ml of each solution, one commercially available contact lens (Menicon Co., Ltd., Menicon EX) was immersed for 18 hours at room temperature. The soaked lens is then removed, a mouse fibroblast L-929 strain is used, a lens is placed on the cell, and an agar overlay test is performed to observe whether the cells under the lens are damaged. The cytotoxicity was examined. When there is an effect of the substance adsorbed on the lens, lysis of cells or neutral red fading is observed, and this case is positive (with cytotoxicity), while the case where such fading is not observed is negative ( No cytotoxicity). Neutral red is a dye added to cultured cells, and is taken up and dyed by living cells, but dead cells discharge it. As a result of the agar overlay test, it was confirmed that the DBDCB used in the present invention was safe without any adsorption to the lens.

[Example 5]
In order to confirm the cleaning effect of the contact lens by the liquid agent of the present invention, a cleaning effect test was performed on the liquid agent No. 4. First, a dirt lens was prepared according to the following procedure.
-Cleaning effect test-
(1) Sorbitan monooleate: 6 w / v%, castor oil: 16 w / v%, lanolin: 35 w / v%, oleic acid: 5 w / v%, sorbitan trioleate: 4 w / v%, cetyl alcohol : 2 w / v%, Cholesterol: 2 w / v%, and Cholesterol acetate: 30 w / v%, mixed 2.5 parts of artificial lipid liquid homogenized by stirring and 97.5 parts of physiological saline Thus, an artificial lipid solution was prepared.

(2) Prepare a hard contact lens (Menicon Super EX: manufactured by Menicon Co., Ltd.) as a test lens, and apply 5 μL of the artificial lipid solution to the surface of each lens evenly on both surfaces of the lens. Obtained.
(3) Then, the obtained artificial lipid-stained lens was taken on the palm of the hand, 0.25 mL of the liquid No. 4 was dropped on this, and rubbed with a fingertip for 10 seconds, and the appearance of the lens surface after washing was visually observed. However, the dirt on the surface of the test lens was removed.
From this, it can be seen that the cleaning effect of the solution of the present invention can be expected.

Claims (6)

A contact lens solution containing 0.15-0.00005 w / v% of 1,2-dibromo-2,4- dicyanobutane . The liquid formulation for contact lenses is, liquid formulation for contact lenses of claim 1, wherein the cleaning storage hard based contact lenses. The contact lens solution according to claim 1, wherein the contact lens solution is used for cleaning and disinfecting a hydrous soft contact lens . The contact lens solution according to claim 2 or 3, further comprising a surfactant.   The contact lens solution according to claim 4, wherein the surfactant is an anionic surfactant or a combination of an anionic surfactant and a nonionic surfactant. Furthermore, the liquid agent for contact lenses of Claim 1 thru | or 5 which contains 1 or more types among the physiologically acceptable buffer, an isotonizing agent, a thickener, and a chelating agent.