JP4827232B2 - Contact lens care products - Google Patents

Description

  The present invention relates to a contact lens care agent having a disinfecting effect. More specifically, the present invention relates to contact lens care agents such as cleaning agents, cleaning preservatives, preservatives, and disinfectants to which hydantoin compounds other than methylolated hydantoins and halogenated hydantoins are added.

  Contact lenses, when worn with dirt such as proteins and lipids, cause problems such as deterioration of wearing feeling and reduced visual acuity, so regular cleaning is indispensable for comfortable and proper wearing. is there. Conventionally, contact lens cleaning preservatives mainly composed of surfactants, buffers, preservatives and the like, and enzyme and contact preservatives for contact lenses containing proteins and lipid stains have been used. More recently, products with antibacterial effects have been developed and marketed for safer and more sanitary contact lens care.

  Soft contact lenses, which are water-containing polymers, are prone to germs and therefore require disinfection when worn. On the other hand, since the oxygen permeable hard contact lens is a non-hydrous material, disinfection treatment is not required. However, in order to handle contact lenses more safely and hygienically, it is preferable to perform disinfection treatment.

  Contact lens care agents include antiseptic sorbic acid and its salts, thimerosal, disinfecting benzalkonium chloride, chlorohexidine, polyhexamethylene biguanide, alkyl (poly) aminoethylglycine hydrochloride, etc. However, each of these antiseptic / disinfectants has problems. For example, sorbic acid and its salt have a yellowing / discoloration over time, and the antiseptic effect is reduced. Thimerosal is already an organic mercury compound, so its use in Japan is already regulated. In addition, quaternary ammonium salt disinfectants such as benzalkonium chloride, biguanide disinfectants such as chlorohexidine, and amphoteric surfactant disinfectants such as alkyl (poly) aminoethylglycine hydrochloride are cationic in aqueous solution. Therefore, when used in combination with an anionic surfactant, the antiseptic / disinfecting effect is reduced or deactivated, and adsorption / accumulation on the lens surface or changes in optical properties are adversely affected to contact lenses. There is a problem of affecting.

  In addition, anionic surfactants and nonionic surfactants that exhibit antiseptic effects such as sodium lauryl sulfate have a high concentration in order to obtain an effect that is higher than antiseptic effects, which adversely affects contact lenses. There are problems such as effects.

  Thus, as a disinfectant for a contact lens care agent, there has been a problem in using a conventionally known antiseptic, a disinfectant that exhibits a cationic property in a water solution, and a surfactant.

  By the way, common disinfectants include chlorine-based disinfectants such as hypochlorous acid, hypochlorite, and hypochlorite esters. The disadvantages of these halogen-based disinfectants in general are that they are less stable in aqueous solution and the effective concentration decreases with time.

  Therefore, the use of a hydantoin compound has been proposed as an active sustaining agent that maintains the activity of effective chlorine in an aqueous solution for a long period of time and enhances the chlorination effect (see Patent Document 1).

  Further, in the field of contact lens care agents, a cleaning / disinfecting agent composed of urea peroxide and a chlorine compound is disclosed (see Patent Document 2). Here, dichlorocyanurate, 1,3-dichloro-5,5-dimethylhydantoin and the like are mentioned as the chlorine-based compound.

  However, even when an active sustaining agent is used for the halogen-based disinfectant, a decrease in effective concentration over time is unavoidable, and it is difficult to prolong the shelf life. Furthermore, since the oxidizing power is very strong and has a bleaching action, when used in a contact lens care agent, there are problems such as decoloration of the contact lens and irritation to the skin and ocular mucosa.

  Further, methylolated hydantoin obtained by reacting formaldehyde with dimethylhydantoin has a preservative effect and is used as a preservative for shampoos in the cosmetics field. For example, an antimicrobial composition comprising a mixture of a condensation composition of 5,5-dimethylhydantoin and formaldehyde and a water-soluble chelating agent is disclosed (see Patent Document 3).

  In the field of contact lens care agents, a methylolated hydantoin, a water-soluble chelating agent, a surfactant, and a cleaning / preserving agent coexisting with an isobutylene-maleic anhydride copolymer as a thickening agent are disclosed ( (See Patent Document 4). Examples of methylolated hydantoins used in these include 1,3-dimethylol-5,5-dimethylhydantoin, 1-methylol-5,5-dimethylhydantoin, and 3-methylol-5,5-dimethylhydantoin. Yes. These compounds are formaldehyde donors formed by the condensation of formaldehyde and hydantoin, and formaldehyde is released over a long period of time even when the methylolated hydantoin content is low. Demonstrate.

  Formaldehyde is known as an antimicrobial agent (aldehyde-based disinfectant) widely used not only for industrial products but also for extending the shelf life of personal care products such as cosmetics.

However, formaldehyde has not only many disadvantages, such as an unpleasant odor, high irritation to the skin and ocular mucosa, and high volatility, making it difficult to extend the shelf life. And oversight by regulatory authorities is becoming increasingly strict.
Japanese Patent Publication No. 56-50638 JP 59-206816 JP-A-55-154906 Japanese Patent No. 2851405 (Japanese Patent Laid-Open No. 4-1343173)

  As disinfecting components in the field of contact lens care agents, quaternary ammonium salt disinfectants, biguanide disinfectants, and amphoteric surfactant disinfectants are generally used.

  However, in an aqueous solution coexisting with an anionic surfactant with excellent detergency as a cleaning component, the formation of an ion complex causes white turbidity / precipitation, which reduces and deactivates both disinfection and cleaning effects. A compatible effect cannot be obtained.

  When a nonionic surfactant is used as a cleaning component, the deterioration of the disinfection effect is small, but since the cleaning power itself is remarkably inferior to that of the anionic surfactant, the disinfection effect and the cleaning effect cannot be achieved at the same time.

  When an amphoteric surfactant having both cationic and anionic properties is used, the ionicity changes depending on the pH of the aqueous solution, so that the effect to be exerted is either disinfection or cleaning. For example, even if the pH of the aqueous solution is controlled, it is difficult to obtain the same effect as when a cationic surfactant or an anionic surfactant is used alone. Absent.

  The methylolated hydantoins described in Patent Document 3 and Patent Document 4 do not exhibit ionic properties in an aqueous solution, and therefore do not reduce the detergency even in the presence of an anionic surfactant.

  However, when used in a contact lens care agent, it is a formaldehyde donor even at a low concentration, and there is still a concern for safety. In addition, since the effect is reduced by decreasing the amount of formaldehyde released from methylolated hydantoin with time, there remains a problem in maintaining the disinfection effect for a long period of time.

  As described above, as a contact lens care agent, even when coexisting with an anionic surfactant having a good cleaning effect, it exhibits a disinfecting effect and is compatible with the cleaning effect, and is highly safe disinfecting. Ingredients were desired.

  An object of the present invention is to provide a contact lens care agent that exhibits good disinfection and cleaning effects. More specifically, an object of the present invention is to provide a contact lens care agent that has both an excellent disinfecting effect and a cleaning effect even in the presence of a surfactant, particularly an anionic surfactant.

  The present invention is a contact lens care agent using a disinfecting component that does not generate formaldehyde or hypochlorous acid in an aqueous solution.

  Specifically, it is a contact lens care agent containing a hydantoin compound excluding methylolated hydantoin and halogenated hydantoin.

  The present invention also provides a contact lens care agent containing a hydantoin compound excluding methylolated hydantoin and halogenated hydantoin and a surfactant.

  Furthermore, the present invention is a contact lens care agent containing a hydantoin compound excluding methylolated hydantoin and halogenated hydantoin, a surfactant, and a proteolytic enzyme.

  By including a hydantoin compound that is useful as a contact lens care agent, it is possible to achieve both an excellent disinfecting effect and a cleaning power, and a safe cleaning agent, preservative, cleaning / preservative, dissolved water, We can provide contact lens care products such as conditioning solutions, rinse solutions, and multipurpose solutions (disinfectants).

  As a result of intensive studies on disinfecting ingredients that are effective even in the presence of surfactants, especially anionic surfactants that exhibit good detergency, in order to solve the above problems, a hydantoin compound that does not unexpectedly generate harmful substances And found that it is possible to achieve both a disinfection effect and a cleaning effect.

  Specifically, the present invention was completed upon obtaining the knowledge that methylolated hydantoins that release harmful substances such as formaldehyde and hydantoin compounds excluding halogenated hydantoins exert favorable effects as a contact lens care agent. It was.

  Hydantoin compounds such as 5,5-dimethylhydantoin are raw materials for halogenated hydantoins such as methylolated hydantoins such as 1,3-dimethylol-5,5-dimethylhydantoin and 1,3-dichloro-5,5-dimethylhydantoins. It is used as organic synthetic raw materials such as water-soluble polymers, various intermediates such as epoxy resins, and pharmaceutical raw materials.

  However, when used as a disinfecting component for contact lens care agents, unlike ionic disinfectants, even in the presence of an anionic surfactant, the detergency is not impaired and the cleaning effect is maintained, and the disinfecting effect is maintained. It is not known to demonstrate.

  Hydantoin compounds that can be used in the present invention include, for example, hydantoin, 5-methylhydantoin, 5-ethylhydantoin, 5-propylhydantoin, 5-isopropylhydantoin, 1-butylhydantoin, 3-butylhydantoin, 5-cyclohexylhydantoin, 5- Phenylhydantoin, 5-benzylhydantoin, 5,5-dimethylhydantoin, 5,5-diethylhydantoin, 5,5-dibutylhydantoin, 5,5-dicyclohexylhydantoin, 5,5-diphenylhydantoin, 1,3-dibenzylhydantoin 3-ethyl-5-phenylhydantoin, 5- (p-methoxyphenyl) hydantoin, 5- (p-hydroxyphenyl) hydantoin, 1-aminohydantoin, 3-aminohydantoin, 5- (3-a Nopuropiru) hydantoin, 1,3-di (aminopropyl) -5,5-dimethyl hydantoin, 1,5-trimethylene hydantoin, and, may be mentioned their sodium salts, potassium salts, and the like. These hydantoin compounds can be used alone or in combination of two or more. Among these, 5,5-dimethylhydantoin can be particularly preferably used.

  Even if it is a hydantoin compound, the compound of the kind which generate | occur | produces a harmful substance like methylolated hydantoin and halogenated hydantoin cannot be used from the surface of safety | security.

  5,5-Dimethylhydantoin can be added to various contact lens care agents, and its blending amount is 0.5 to 13.5 (W / V)%, preferably 1.0 to 6. The range is 5 (W / V)%. This is because if it is less than 0.5%, the disinfection effect is not sufficient, and if it exceeds 13.5%, no significant improvement in disinfection effect is observed.

  The present invention is preferably a contact lens care agent containing a hydantoin compound excluding methylolated hydantoin and halogenated hydantoin, and a surfactant. In the case of the contact lens care agent of the present invention, the solution containing 5,5-dimethylhydantoin is selected from an anionic surfactant, a cationic surfactant, a nonionic surfactant, and an amphoteric surfactant. A selected surfactant can be added. When it is desired to improve the cleaning effect, it is preferable to add an anionic surfactant or a combination of an anionic surfactant and a nonionic surfactant.

  Anionic surfactants include alkyl sulfonates such as sodium lauryl sulfate and triethanolamine lauryl sulfate, alkylbenzene sulfonates such as sodium dodecylbenzenesulfonate and triethanolamine dodecylbenzene, sodium polyoxyethylene lauryl ether sulfate And polyoxyethylene alkyl ether sulfates such as polyoxyethylene lauryl ether sulfate triethanolamine, and α-olefin sulfonates such as sodium α-olefin sulfonate.

  Nonionic surfactants include polyoxyethylene alkyl ethers such as polyoxyethylene lauryl ether, polyoxyethylene alkyl phenyl ethers such as polyoxyethylene nonylphenyl ether, and polyoxyethylene polyethers such as polyoxyethylene polyoxypropylene cetyl ether. Examples thereof include alkylol amides such as oxypropylene alkyl ether, coconut oil fatty acid diethanolamide, and lauric acid diethanolamide.

  Examples of amphoteric surfactants include alkylbetaine types such as alkyldimethylaminoacetic acid betaine, alkylamide betaine types such as coconut oil fatty acid amidepropylbetaine, glycine types such as alkyldiaminoethylglycine hydrochloride, N- [3-alkyl (12, 14) Oxy-2-hydroxypropyl] -L-arginine hydrochloride and the like.

  The amount of these surfactants is not particularly limited as long as the concentration does not adversely affect the disinfection effect of the contact lens, hydantoin compound, and the stability of the proteolytic enzyme, and does not irritate the eyes. Preferably it is 0.05-20 (W / V)%, More preferably, it is the range of 0.1-5 (W / V)%.

  The present invention is preferably a contact lens care agent containing a hydantoin compound excluding methylolated hydantoin and halogenated hydantoin, a surfactant, and a proteolytic enzyme. In particular, when it is desired to improve the cleaning effect of protein soil, a proteolytic enzyme can be added to a solution containing 5,5-dimethylhydantoin and a surfactant. Proteolytic enzymes include plant-derived proteases such as papain, bromelain, gradient, and ficin, animal-derived proteases such as trypsin, chymotrypsin, and pancreatin, and microorganism-derived proteases such as bacterial proteases produced by bacteria such as Bacillus. Any of these can be used.

  Among the above-mentioned proteolytic enzymes, a bacterial protease derived from the genus Bacillus is preferable because of the stability of the enzyme in an aqueous solution containing a surfactant, particularly an anionic surfactant. Examples of such proteolytic enzymes include “Biolase” (manufactured by Nagase Seikagaku Corporation), “Subtilisin A”, “Alcalase”, “Esperase”, “Sabinase” (manufactured by Novozymes), “Protease N Amano” (Amano Pharmaceutical Co., Ltd.). The amount of proteolytic enzyme is appropriately determined based on the effective amount corresponding to the cleaning effect, but is preferably 0.01 to 10 (W / V)%, more preferably 0.05 to The range is 5 (W / V)%.

  In order to improve the stability of the proteolytic enzyme in the presence of a surfactant, a water-soluble polyhydric alcohol and trimethylglycine can be added.

  There are no particular restrictions on the type of water-soluble polyhydric alcohol, and examples include glycerin, sorbitol, ethylene glycol, propylene glycol, dipropylene glycol, and 1,3-butylene glycol, but preferably suppress the growth of microorganisms. Propylene glycol, dipropylene glycol and 1,3-butylene glycol having bacteriostatic action.

  The compounding amount is not particularly limited as long as it is a concentration that does not adversely affect the cleaning power and contact lens as a cleaning preservative for contact lenses, but considering the stability of the proteolytic enzyme, and the properties and tactile sensation. , Preferably 5 to 50 (W / V)%, more preferably 10 to 35 (W / V)%. If it is less than 5%, the stability of the proteolytic enzyme is not sufficient, and if it exceeds 50%, no significant improvement in stability is observed.

  Further, the blending amount of trimethylglycine is preferably in the range of 3 to 15 (W / V)%, more preferably 5 to 15 (W / V)%, and the blending amount of the water-soluble polyhydric alcohol and trimethylglycine is The total is preferably in the range of 8 to 65 (W / V)%, more preferably 10 to 45 (W / V)%. If it is less than 8%, the stability of the proteolytic enzyme is not sufficient, and if it exceeds 65%, not only a significant improvement in stability is not observed, but also the detergency does not appear, and the properties and feel are It becomes unsuitable as a contact lens care agent.

  The contact lens care agent of the present invention is preferably prepared in the range of about pH 5-9, more preferably about pH 6-8, so as not to cause irritation to the eyes or adverse effects on the contact lens. Therefore, in this invention, a buffering agent is added as needed.

  As the buffering agent, a buffering agent that does not impair the disinfecting effect, the cleaning effect, and the stability of the proteolytic enzyme is appropriately selected and used. Specific examples include a buffering agent combining trishydroxymethylaminomethane and hydrochloric acid or citric acid, a buffering agent combining boric acid and / or borax, and the like, and preferably a static agent that suppresses the growth of microorganisms. It is a buffering agent combining boric acid and / or borax that has fungal action and contributes to the stabilization of proteolytic enzymes.

  The blending amount of the buffering agent is preferably in the range of 0.1 to 10 (W / V)%. If the pH is less than 0.1 (W / V)%, sufficient pH stability cannot be obtained, and if it exceeds 10 (W / V)%, notable stability of pH is not recognized, but at low temperatures. In the case of storage, there is a possibility that problems such as precipitation of a buffering agent may occur.

  In the present invention, a thickener, a pH adjuster, a chelating agent, and other enzyme agents may be added in addition to the above components as long as the object, effect, and action of the present invention are not inhibited. For example, natural and synthetic water-soluble polymers with thickening action include polyethylene oxide, polyvinyl alcohol, polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, carboxymethyl cellulose, pullulan, sodium alginate, sodium chondroitin sulfate, phospholipid analog Examples of the polymer include poly (meth) acryloyloxyethyl phosphorylcholine, and the like can be used alone or in appropriate combination.

  Of the above components, polyvinyl alcohol, hydroxypropylmethylcellulose, and poly (meth) acryloyloxyethyl phosphorylcholine are preferably used as components that can be expected to improve the hydrophilicity of the lens surface in addition to the thickening action. In particular, poly (meth) acryloyloxyethyl phosphorylcholine is easily available commercially and is suitable for the contact lens care agent of the present invention, and is usually used in the range of 0.01 to 10 (W / V)%. It is done.

  As pH adjusters, hydrochloric acid, phosphoric acid, sodium hydroxide and the like, edetates such as disodium edetate as chelating agents, and lipolytic enzymes and the like as enzyme agents can be added in appropriate amounts.

  The present invention can be used as a dosage form such as granules, powders, tablets, gels and the like prepared at the time of use according to the purpose.

  EXAMPLES Hereinafter, the present invention will be specifically described by way of examples, but these examples do not limit the present invention. The unit in the examples is W / V% unless otherwise specified.

(Examples 1-5, Comparative Examples 1-4)
Each formulation component described in Table 1 was mixed and dissolved in purified water to prepare each formulation of the contact lens care agents of Examples and Comparative Examples, and the following evaluation tests were performed.

[1. Disinfection and disinfection effect]
Disinfection / disinfection effects of the contact lens preservatives of Example 1 and Comparative Example 1, the contact lens cleaning preservatives of Examples 2 to 4 and Comparative Examples 2 to 4, and the contact lens disinfectant of Example 5 The following procedure evaluated.

As test strains, three types of bacteria, Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC6538), and spirit fungus (Serratia marcescens: ATCC13880), and fungi of Candida albicans (ATCC 10231) One type was used. For bacteria, a suspension (10 ⁸ to 10 ⁹ cfu) collected by adding sterilized Dulbecco's phosphate buffered saline to the mycelia obtained by culturing at 35 ° C. for 24 hours on a sloped medium of soybean casein agar medium / mL) was used as the test bacterial stock solution. For fungi, a suspension (10 ⁸ to 10 ⁹ cfu) collected by adding sterilized Dulbecco's phosphate buffered saline to the mycelia obtained by culturing at 35 ° C. for 24 hours on a gradient medium of glucose peptone agar medium / mL) was used as the test bacterial stock solution.

10 mL of the contact lens solution sterilized in advance was inoculated with 0.1 mL of each stock solution of the above test bacteria so as to have a final concentration of 10 ⁵ to 10 ⁶ cfu / mL, and then stored in an incubator at 25 ° C. After the predetermined disinfection time, 1 mL of each test solution after inoculation of microorganisms is collected, added to 9 mL of liquid medium (Letheen Broth) with sterilized inactivator (diluted 10 times), and further sterilized Dulbecco's phosphate buffer Prepare a series of 10-fold dilutions using physiological saline, take 1 mL of the test solution diluted at 3 concentrations at an appropriate dilution ratio in a sterilized disposable dish, add the agar medium, and pour it to count the number of viable bacteria. It was measured.

  On the other hand, for the initial bacterial count inoculated into the contact lens solution (initial inoculated bacterial count), the number of viable bacteria was measured by the same operation as described above using sterilized Dulbecco's saline for all dilutions. As the agar medium, soybean casein agar medium was used for bacteria, and glucose peptone agar medium was used for fungi. The culture conditions in this agar pour plate method were 35 ° C. × 48 hours for both bacteria and fungi. The logarithmic difference after the disinfection time (logarithm of the number of viable bacteria decreased) is calculated by calculating the number of initial bacteria and the number of live bacteria (logarithmic value) of the test solution after inoculation. It calculated | required from the difference of the numerical value and the logarithm value of the viable count of a test liquid after inoculation.

Logarithmic difference (logarithm of viable cell count reduction) =
Initial number of bacteria (logarithmic value)-Number of viable bacteria in test solution after inoculation (logarithmic value)

  The criteria for disinfection are based on the primary standards for ISO stand-alone tests, and the logarithmic difference at a given disinfection time passes the logarithmic difference of 3.0 or higher for bacteria and the logarithmic difference of 1.0 or higher for fungi. It was. The test was conducted with a disinfection time of 6 hours.

[2. Cleaning effect]
The cleaning effects of the contact lens cleaning preservatives of Examples 2 to 4 and Comparative Examples 2 to 4 were evaluated by the following procedure.

(Production of artificial dirt lens)
An oxygen-permeable hard contact lens (Seed Co., Ltd., Seed A-1) is immersed in a known artificial tear component (protein, lipid, and inorganic salt) as a test lens and heated at 55 ° C. for 5 hours. To do. Further, the lens was immersed in pure water at 70 ° C. for 16 hours and then dried at 50 ° C. for 6 hours to produce an artificial dirt lens.

(Detergency test)
Artificial dirt lenses whose haze values before washing were measured in advance were soaked in the cleaning agents of Examples and Comparative Examples for 6 hours, rinsed lightly with pure water after 6 hours, and then naturally dried. . The haze value of the lens after washing was measured, and the stain removal rate was calculated.

(Evaluation methods)
The cleaning effect was evaluated by measuring the haze value (turbidity) before and after cleaning the artificial dirt lens. For measurement of the haze value, a fully automatic haze computer HGM-2DP manufactured by Suga Test Instruments Co., Ltd. was used, and the dirt removal rate was calculated according to the following formula.

(Haze value before cleaning-Haze value after cleaning)
Dirt removal rate (%) = ―――――――――――――――――――――――― × 100
(Haze value before cleaning)

From the calculated dirt removal rate (%), the cleaning power was evaluated in five stages as shown below. The results are shown in Table 3.
◎; 90% or more ○; 80 to less than 90% △; 60 to less than 80% ▲; 40 to less than 60% ×; less than 40%

* The compounding amount of the surfactant is the compounding amount after conversion to the pure component.

Surfactant 1: Lauryldimethylaminoacetic acid betaine (Toho Chemical Co., Ltd .: Obazoline BC)
Surfactant 2: α-olefin sulfonate sodium (Lion Corporation: Lipolane PJ-400)
Surfactant 3: POE-POP block polymer (BASF Japan KK: Lutrol F-127)
* Proteolytic enzyme: Novozymes, Inc .: CL-Pro2.5MG

  Although Examples 1-5 have the disinfection effect which satisfy | fills the primary implementation standard of an ISO stand-alone test with respect to bacteria and fungi with disinfection time 6 hours, it is that the disinfection effect is remarkably inferior in Comparative Examples 1-4. I can confirm.

  As contact lens cleaning / preservatives, Examples 2 to 4 and Comparative Example 2 show high cleaning power, but Comparative Examples 3 and 4 confirm that the cleaning effect is remarkably inferior.

From the above evaluation results, contact lens preservatives, contact lens cleaning preservatives,
Usefulness as a contact lens care agent such as a contact lens disinfectant can be confirmed. In particular, it can be seen that the contact lens cleaning preservatives of Examples 2 to 4 are compatible with the disinfection effect even when an anionic surfactant having a good cleaning effect is used.

Claims (2)

A contact lens care agent, comprising 5,5-dimethylhydantoin and a surfactant. 2. The contact lens care agent according to claim 1, wherein the care agent is a preservative, a cleaning agent, a cleaning preservative, or a disinfectant.