JP5989326B2 - Solvent for contact lenses - Google Patents

Description

The present invention relates to a contact lens solvent for caring for contact lenses.

When a contact lens is worn on the eye, protein and lipid stains derived from tears and eyelids adhere to the lens surface. These stains serve as a hotbed for bacterial growth and can affect the risk of eye disease, reduced contact lens wear and vision correction.

Contact lenses are roughly classified into hard contact lenses and soft contact lenses. Among these, soft contact lenses tend to cause microorganisms to proliferate due to moisture in the contact lenses, and may cause serious problems to eye tissues when sufficient care is not taken.

Therefore, in order to use the soft contact lens safely and hygienically, it is important to sufficiently clean and disinfect the lens and to keep it clean.

By the way, in the process of contact lens care, “cleaning” to remove dirt attached to the surface, “disinfection” to detoxify microorganisms, “rinsing” after cleaning and disinfection, “storage” to maintain performance There is. In terms of hygiene, it is desired to distinguish between cleaning and subsequent disinfection, rinsing and storage, and to treat each using a dedicated solution. However, in recent years, multi-purpose solutions that can perform all processes with a single solution have become widespread because of their simplicity.

Processing with a multi-purpose solution is called cold disinfection. The cold disinfection method is a treatment method for cleaning and disinfecting soft contact lenses with a disinfecting component blended in a liquid. In this case, organic nitrogen-based disinfectants are mainly used as disinfecting components.

In a multi-purpose solution, attempts have been made to incorporate a high concentration of disinfecting ingredients in order to enhance the disinfecting effect. However, a high concentration of disinfecting components is toxic to the eye tissue and has a safety problem. Therefore, the blending amount of the disinfecting component is limited and is generally 1.0 × 10 ⁻⁴ (W / V%) or less. However, at such a concentration, the disinfection effect on the soft contact lens is not sufficient.

Thus, in order to enhance the disinfection effect on soft contact lenses, a method of using polyhexamethylene biguanide, which is a kind of organic nitrogen-based disinfectant, with a high concentration of nonionic tonicity agent has been known so far. (See Patent Document 1).

In addition, as an antibacterial agent containing high molecular weight polyamine sulfone and N- (hydroxyalkyl) -aminoethanol as a disinfecting component (patented) as a means to prevent the growth of microorganisms in industrial water, which is a technical field different from contact lens solvents Document 2) and antimicrobial agents (see Patent Document 3) containing polyamine sulfone having a low molecular weight as a disinfecting component are known.

JP-A-10-108899 JP-A-01-294602 Japanese Patent Application Laid-Open No. 11-049610

The solvent for contact lenses of patent document 1 mix | blends polyhydric alcohols, such as glycerol and propylene glycol which are nonionic tonicity agents, with high concentration. When a soft contact lens is processed using a solvent in which a polyhydric alcohol is mixed at a high concentration, there is a possibility that the optical characteristics will be adversely affected, such as swelling and deformation of the contact lens.

Regarding the disinfecting effect of the polyamine sulfone used in Patent Documents 2 and 3, since the disinfecting effect of the polyamine sulfone described in Patent Document 2 is very small, the disinfecting effect of N- (hydroxyalkyl) -aminoethanol used together is It is used as an enhancement aid. Moreover, although the polyamine sulfone of patent document 3 has a disinfection effect, it has irritation. Therefore, when the polyamine sulfone described in Patent Document 3 is used as a disinfecting component of the solvent for contact lenses, there is a possibility of adversely affecting the eye tissue.

Therefore, when used as a contact lens solvent, the disinfectants described in Patent Documents 1 to 3 have problems with respect to the adverse effect on the shape of the contact lens, the disinfection effect, and the safety to the eye tissue.

Therefore, in view of the above problems, an object of the present invention is to provide a contact lens solvent that does not adversely affect the shape of the contact lens, has a disinfecting effect on fungi and the like, and has safety for eye tissues. is there.

The present inventors diligently studied the means for solving the above problems, and as a result, the disinfection effect and safety to the eye tissue of the compound applied as the disinfecting component of the contact lens solvent have an influence on the molecular weight and the compounding amount. I thought it would be received.

That is, the polyamine sulfone described in Patent Document 3 has a molecular weight of 5,000, and when such a compound is used as a disinfecting component of a solvent for contact lenses, the disinfecting effect can be expected, but the irritation is strong. There is a high possibility of adverse effects on the eye tissue.

In contrast to this, the polyamine sulfone described in Patent Document 2 having a molecular weight of 90,000 to 1,200,000 has a low disinfection effect although it has safety to the eye tissue, and has a desired disinfection effect. If an attempt is made to prepare a solvent for contact lenses, such a compound must be blended at a high concentration, which may cause adverse effects on ocular tissues.

Therefore, the present inventors proceeded with research and development on disinfecting components suitable for solvent for contact lenses, taking into consideration the disinfecting effect and safety to the eye tissue, focusing on the molecular weight and compounding amount of the compound. A combination of an organic nitrogen-based disinfectant used as a disinfecting component for contact lens solvents and a diallyldialkylammonium-containing polymer having a certain molecular weight is suitable for disinfecting effects and ocular tissues suitable for contact lens solvents. It has been found that it has safety.

The diallyldialkylammonium-containing polymer is used for a dye fixing agent, a cationizing agent, an inkjet fixing agent, a cosmetic raw material, and the like, and is also known to have antibacterial properties alone.

However, a diallyldialkylammonium-containing polymer alone exhibits a disinfecting effect only when the molecular weight is low. When the diallyldialkylammonium-containing polymer has a high molecular weight, it can be presumed that the disinfecting site in the molecule hardly acts on the object to be disinfected due to its steric hindrance. Therefore, when a high molecular weight diallyldialkylammonium-containing polymer is used at a concentration within a range that is safe for eye tissues, a disinfection effect suitable for a solvent for contact lenses cannot be obtained.

However, a combination of the organic nitrogen-based disinfectant and a diallyldialkylammonium-containing polymer having a certain molecular weight has a cleansing effect, is highly safe for ocular tissues, and is free of bacteria and It has a disinfecting effect on microorganisms including fungi, and surprisingly, the adverse effect on the contact lens shape is very small. Therefore, such a thing is very suitable as a solvent for contact lenses.
The present invention has been completed based on the above findings.

Therefore, according to this invention, the solvent for contact lenses which mix | blends an organic nitrogen type disinfectant and the diallyl dialkyl ammonium containing polymer whose molecular weight is 15,000-150,000 is provided.

Preferably, the solvent for contact lenses of the present invention contains the diallyldialkylammonium-containing polymer in a ratio of 0.005 to 1.0 with respect to the organic nitrogen-based disinfectant 1.0 × 10 ⁻⁴ .

Preferably, in the contact lens solvent of the present invention, the diallyldialkylammonium-containing polymer is selected from the group consisting of a polymer of diallyldimethylammonium chloride and a copolymer of diallyldimethylammonium chloride, sulfur dioxide and maleic acid. At least one polymer.

Preferably, in the contact lens solvent of the present invention, the organic nitrogen-based disinfectant is at least one disinfectant selected from the group consisting of a biguanide-based disinfectant and a quaternary ammonium-based disinfectant.

The solvent for contact lenses of the present invention can be blended with an organic nitrogen-based disinfectant in a blending amount within the range of application to a multi-purpose solution, and the organic nitrogen-based disinfectant is mixed with a diallylalkylammonium-containing polymer having a constant molecular weight. By combining and blending, it has a high disinfecting effect suitable as a solvent for contact lenses and a high safety for ocular tissues.

Therefore, according to the solvent for contact lenses of the present invention, the surface of the contact lens can be kept clean, in addition to reducing the risk of eye damage caused by the adhesion of microorganisms, and the oiliness of the contact lens surface It is possible to avoid a decrease in wearing feeling of the contact lens due to dirt or a change in the shape of the contact lens, an obstacle related to visual acuity correction, and the like.

Details of the present invention will be described below.
The solvent for contact lenses of the present invention contains an organic nitrogen-based disinfectant and a diallyldialkylammonium-containing polymer having a molecular weight of 15,000 to 150,000 in combination, thereby enhancing the disinfecting effect and improving the disinfecting effect. High safety.

In relation to the above problem, the molecular weight of the diallyldialkylammonium-containing polymer to be blended becomes important. The molecular weight of the diallyldialkylammonium-containing polymer is 15,000 to 150,000, preferably 20,000 to 100,000. If the molecular weight is less than 15,000, the disinfection effect is improved, but the safety to the eye tissue is significantly reduced. On the other hand, if the molecular weight exceeds 150,000, the viscosity of the resulting solvent becomes high, resulting in problems in handling.

Examples of the diallyldialkylammonium-containing polymer used in the present invention include a diallyldialkylammonium salt polymer, a diallyldialkylammonium salt and a compound having a polymerizable functional group (—C═C—) or a polymerizable compound, and the like. The polymer is not particularly limited as long as it is a polymer obtained by copolymerization of Examples of diallyldialkylammonium salts include, but are not limited to, diallyldialkylammonium hydrochloride, sulfate, acetate, and amide sulfate. Examples of the diallyldialkylammonium-containing polymer include, for example, a polymer of diallyldimethylammonium chloride and diallylmethylethylammonium chloride, and a compound capable of copolymerizing with diallyldimethylammonium chloride and diallylmethylethylammonium chloride, specifically, Examples thereof include copolymers with sulfur dioxide, acrylamide, epichlorohydrin, maleic acid, and the like. Each polymerization component can be used alone or in combination of two or more.

Particularly preferred in the present invention are diallyldimethylammonium chloride polymers, diallyldimethylammonium chloride sulfur dioxide copolymers and diallyldimethylammonium chloride sulfur dioxide-introduced copolymers. Specific examples of the diallyldimethylammonium chloride sulfur dioxide-introduced copolymer include a copolymer of diallyldimethylammonium chloride, sulfur dioxide, and maleic acid. For example, the copolymer is represented by the following general formula (1).
(In the formula, n, m and l are determined as long as the molecular weight of the polymer is within the range shown above.)

A polymer of diallyldimethylammonium chloride having a molecular weight of 15,000 to 150,000 is provided, for example, as a product name “PAS-H-8L” by NITTO BOO MEDICAL CO., LTD, Japanese Patent Laid-Open No. 2000-063435 Referring to the description in paragraphs 0080 to 0082, the polymer can be produced by modifying the polymerization conditions and the like so as to obtain an appropriate molecular weight. A copolymer of diallyldimethylammonium chloride, sulfur dioxide, and maleic acid is provided, for example, as a product name “PAS-84” by NITTO BOO MEDICAL CO., LTD. Description in paragraph 0038 of JP 2010-248460 A Can be produced by modifying the polymerization conditions and the like so as to obtain an appropriate molecular weight.

The organic nitrogen-based disinfectant used in the present invention is not particularly limited as long as it is an organic nitrogen-based disinfectant used for contact lens care. For example, biguanide-based disinfectants such as polyhexamethylene biguanide and polyaminopropyl biguanide. And quaternary ammonium-based disinfectants such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium chloride. In the present invention, a biguanide disinfectant is preferably used, and polyhexamethylene biguanide is particularly preferable. As the organic nitrogen-based disinfectant, a commercially available one may be used, or one produced by a known method may be used.

In the contact lens solvent of the present invention, the diallyldialkylammonium-containing polymer is preferably adjusted and used so as to have a certain ratio with respect to the blending amount of the organic nitrogen-based disinfectant. For example, the blending amount of the diallyldialkylammonium-containing polymer is preferably 0.005 to 1.0, more preferably 0.0075 to 0.5, with respect to the blending amount 1.0 × 10 ^{−4 of} the organic nitrogen-based disinfectant. More preferably, by setting the content to 0.01 to 0.1, it is possible to obtain an antiseptic effect enhanced while having the same amount of disinfecting components as the conventional multipurpose solution for contact lenses. is there. More specifically, when the compounding amount of the organic nitrogen-based disinfectant is 1.0 × 10 ⁻⁴ W / V%, the compounding amount of the diallyldialkylammonium-containing polymer is 0.005 to 1.0 W / V%. Is preferred.

When the blending amount of the diallyldialkylammonium-containing polymer is less than 0.005 with respect to the organic nitrogen-based disinfectant 1.0 × 10 ⁻⁴ , the disinfecting effect is not sufficiently enhanced. It is strong and cannot keep safe.

The compounding amount of the organic nitrogen-based disinfectant is not limited as long as it is within the range used in a normal multi-purpose solution for contact lenses, but considering disinfection, 5.0 × 10 ⁻⁵ W / V% or more Is more preferable, and more preferably 9.0 × 10 ⁻⁵ W / V% or more. In consideration of safety such as eye irritation, it is preferably 2.0 × 10 ⁻⁴ W / V% or less, more preferably 1.5 × 10 ⁻⁴ W / V% or less.

In addition to the organic nitrogen-based disinfectant and the diallyldialkylammonium-containing polymer, the solvent for contact lenses of the present invention improves the detergency against dirt such as lipids and proteins attached to the contact lens. A surfactant selected from a cationic surfactant, a nonionic surfactant and an amphoteric surfactant can be added. In the present invention, a nonionic surfactant is preferably used in consideration of the influence on the optical properties such as deformation of the contact lens during cleaning.

Nonionic surfactants include, for example, poly (oxyethylene) -poly (oxypropylene) block copolymers, polyoxyethylene alkyl ethers, polyoxyethylene alkyl phenyl ethers, polyoxyethylene alkyl esters, polyoxyethylene sorbitan alkyl esters. In the present invention, a poly (oxyethylene) -poly (oxypropylene) block copolymer is most preferred. A compounding quantity is 0.01-5.0 W / V% normally used as a solvent for contact lenses, More preferably, it is 0.05-1.0 W / V%.

The solvent for contact lenses of the present invention takes into consideration eye irritation and the stability of contact lens materials, for example, pH 6.4 to 8.4, preferably 6.9 to 7.9. Add buffer.

Examples of the buffer include a phosphate buffer, a borate buffer, a citrate buffer, a trishydroxyaminomethane buffer, and the like. In the present invention, in view of the effect of inhibiting the growth of microorganisms, a borate buffer is used. An agent is preferably used.

When the concentration of the buffering agent is too low, the desired buffering effect cannot be obtained, and when it is too high, there is a concern about eye irritation and precipitation at low temperatures. 0 W / V%, more preferably 0.05 to 2.0 W / V%.

In addition to the above components, the solvent for contact lenses of the present invention includes, in addition to chelating agents, tonicity agents, thickeners, proteolytic enzymes, lipolytic enzymes, etc., as long as the object of the present invention is not impaired. Various additives such as enzyme agents can be further blended.

Specifically, as a chelating agent, ethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid / disodium, ethylenediaminetetraacetic acid / trisodium, citric acid; as an isotonic agent, glycerin, propylene glycol, sorbitol, mannitol; as a thickener; Examples thereof include polyvinyl alcohol and hydroxypropyl methylcellulose.

The solvent for contact lenses of the present invention can be produced without particular limitation according to the method for producing a solvent for contact lenses known by those skilled in the art. For example, it can be produced by adding an organic nitrogen-based disinfectant and a diallyldialkylammonium-containing polymer to purified water simultaneously or before and after each. Other components can also be added at the same time or before or after them.

The solvent for contact lenses of the present invention can be produced by comprehensively evaluating the disinfection effect and safety shown in the examples. For example, the contact lens solvent of the present invention has a disinfecting effect of 3.0 or more, preferably 3.3 or more for Staphylococcus aureus, and 1.0 or more, preferably 1.5 or more for Candida albicans, and The safety is 90% or more, preferably 92% or more for 10 V / V%. Further, the contact lens solvent of the present invention is preferably one that does not swell the contact lens and does not affect the shape of the contact lens.

The contact lens of the present invention can be used not only as a contact lens care solvent, as a contact lens disinfection, but also for cleaning, rinsing and storing the contact lens with a composition. The solvent for contact lenses of the present invention is a solvent for contact lenses suitable for the care of soft contact lenses.

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited or limited by these examples.

In accordance with the formulation shown in Table 1, each of the components described in Table 1 for the contact lens care solvents of Examples 1 to 2 or Comparative Examples 1 to 9 of the present invention (diallyldialkyl-containing polymers are weighed in terms of pure content). Was weighed into 100 mL of purified water and sufficiently stirred at room temperature so that each component was uniform. The obtained uniform solution was sterilized by filtration with cellulose acetate having a pore diameter of 0.2 μm to prepare each contact lens solvent. In addition, the following commercially available contact lens care solvents were used as Comparative Examples 10 to 12: Comparative Example 10: Renew Fresh (manufactured by Boschrom Japan), Comparative Example 11: Opti-Free Plus (manufactured by Nippon Alcon) Comparative Example 12: Soft One Moist (manufactured by Rohto Pharmaceutical). About these Examples 1-2 and Comparative Examples 1-12, the disinfection effect was evaluated in accordance with the method shown below. The results are shown in Table 2.

[1. Disinfection effect]
As test strains, three types of bacteria, Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 9027) and spirit fungus (Serratia marcescens: ATCC 13880), and Candida CC102 for Candida CC102 It was.

For both bacteria and fungi, Dulbecco's phosphate buffer was added to the mycelia cultured on a slope medium of an agar medium at 35 ° C. for 18 hours, and the liquid recovered after suspension was used as the mycelia. Furthermore, the mycelia were diluted with Dulbecco's phosphate buffer to adjust the concentration to 10 ⁵ to 10 ⁶ (cfu / mL), and this was used as a fungus test solution. As for the agar medium used, bacteria are soy bean casein agar medium and fungi are glucose heptone agar medium.

The bacterial inoculum obtained by inoculating 10 mL of each sample of Examples 1-2 and Comparative Examples 1-12 with 0.1 mL of the bacterial test solution was allowed to stand in a 25 ° C. incubator for a predetermined disinfection time (4 hours).

After standing, 1 mL of the bacterial inoculum was added to 9 mL of an inert agent-containing medium (Neutralizing Broth) (diluted 10-fold), and further a 10-fold diluted series was continuously prepared with Dulbecco's phosphate buffer. 1 mL of a test solution at 3 concentration points with an appropriate dilution factor that is around 10 to 10 ³ (cfu / mL) was dispensed into a disposable dish, and an agar medium was poured and mixed to determine the number of viable bacteria.

The initial bacterial count, which is the bacterial count of the test bacterial solution, was prepared in the same manner as described above by continuously preparing a 10-fold dilution series with Dulbecco's phosphate buffer.

The culture conditions in this agar pour plate method were 35 ° C. × 48 hours for both bacteria and fungi.

From the obtained initial bacterial count and the viable count (logarithmic value) of each sample inoculated with the test bacterial solution, the logarithmic difference (decreased viable count) after the disinfection time in each sample was obtained from the following formula:
Decrease in viable cell count = initial cell count-viable cell count in the data

The amount of reduction (logarithm) of the number of viable bacteria determined by the above formula was defined as the disinfection effect. The determination of the disinfection effect is usually 3.0 or more for bacteria and 1.0 or more for fungi in the disinfection time after 4 hours according to the primary standard of the ISO stand-alone test. About thing, it is said that it has the disinfection effect with respect to each microbial species. In addition, when comparing the disinfection ability between samples, if the difference in the number of viable bacteria in the same bacterial species was 0.5 or more, the disinfection effect was significantly different between samples. .

[2. safety]
Chinese hamster lung-derived cells V79 cells precultured in a CO ₂ incubator at 37 ° C. were treated with trypsin, and then suspended in Eagle's fetal serum-containing Eagle's minimum essential medium to obtain a cell suspension.

After dispensing each medium prepared so that the sample concentration (V / V%) is 20%, 10%, 5%, and 2.5% in the well of the culture plate, the number of cells should be 100. The suspension was added and cultured in a 37 ° C. incubator for 7 days. As a comparative control, a cell cultured in the same condition in a medium was prepared.

The relative colony formation rate at each concentration point of each sample was determined from the following formula:
Relative colony formation rate (%) = (number of colonies at each concentration point / number of colonies for comparison) × 100

The relative colony formation rate (%) was taken as the safety to the eye tissue as it was. The safety between each sample was evaluated by comparing the relative colony formation rates at the same concentration. The results are shown in Table 2.

[3. Shape stability]
2week ACUVUE and ACUVUE ADVANCE (both manufactured by Johnson & Johnson) were used as test lenses.

After removing the contact lens from the blister package and removing the moisture on the surface, the contact lens was immersed in the solvent for contact lens care of Examples 1 and 2 and Comparative Examples 8 and 9 dispensed in the lens case. It was allowed to stand at room temperature for an hour.

Thereafter, in each solvent, the diameter of the contact lens was measured using a measuring microscope.

The shape stability was determined according to the contact lens approval standard, and the case where the amount of change in diameter before and after immersion in the solvent was within ± 0.2 mm with respect to the numerical value displayed on the product was regarded as acceptable. The results are shown in Table 3.

As the above results show, according to the present invention, compared with the contact lens care solvent sold as a marketed multi-parse solution, the influence on the contact lens shape is small, and it has a high disinfection effect. In addition, a contact lens solvent having safety equivalent to or higher than that can be obtained.

Claims (3)

For contact lenses containing organic nitrogen-based disinfectant , diallyldialkylammonium-containing polymer having a molecular weight of 15,000 to 100,000, hydroxypropylmethylcellulose, D-mannitol and sodium chloride , and not amino acids and amino acid salts solvent. The solvent for contact lenses of Claim 1 which mix | blends the said diallyl dialkyl ammonium containing polymer in the ratio of 0.005-1.0 with respect to the said organic nitrogen type disinfectant 1.0x10 < ^-4 >. The diallyldialkylammonium-containing polymer is at least one polymer selected from the group consisting of a polymer of diallyldimethylammonium chloride and a copolymer of diallyldimethylammonium chloride, sulfur dioxide and maleic acid. Or the solvent for contact lenses of 2.