JP2006201247A - Sterilizing storage solution for contact lens - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a sterilizing storage solution for a contact lens which has superior sterilizing effect and superior safety to the eye, and is suitably used for especially a water-containing contact lens. <P>SOLUTION: The sterilizing storage solution for the contact lens is characterized by containing ε-polylysine, an organic cationic compound, and lactic acid in an aqueous medium. Alternatively the sterilizing storage solution for the contact lens characterized by containing ε-polylysine, an organic cationic acid, lactic acid, and further inositol or glycerol in the aqueous medium. The amount of such a sterilizing storage solution for the contact lens is greatly reduced to low by preparing an environment where antibacterial activity of ε-polylysine as an antibacterial (sterilizing) component can be exhibited to the utmost and the safety of the sterilizing storage solution for the contact lens is therefore further improved. Consequently even when the contact lens is dipped for a long time, there is no influence on the contact lens and sterilized contact lens can be worn at ease. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a disinfecting preservation solution for contact lenses, and particularly relates to a disinfecting preservation solution for contact lenses that has an excellent disinfecting effect, is excellent in eye safety, and is particularly suitable for use in a hydrous contact lens. .

  In general, it is known that by wearing a contact lens, dirt such as proteins contained in tears and lipids derived from eyelids adhere to the contact lens. These stains need to be thoroughly removed by daily cleaning, and the accumulation of stains due to neglect of this operation not only adversely affects the optical performance of the lens, but also bacteria attached to the contact lens surface grow. Since the growth of these bacteria in the warm bed may cause adverse effects such as infection on the eyes, contact lenses, especially hydrous contact lenses, need to be disinfected as well as daily cleaning. .

  Conventionally, a generally used method for disinfecting a hydrous contact lens is by boiling. In this method, boiling sterilization is generally performed at a high temperature in the vicinity of the boiling point of physiological saline using a dedicated sterilization apparatus and container for hydrous contact lenses. Although this boiling disinfection has a high disinfection effect, it is mentioned that special equipment is necessary and the patient's compliance is poor due to complicated operation, and in boiling disinfection, the lens deteriorates due to heat or adheres to the lens In some cases, protein alleviation was caused and allergic reactions such as giant papillary conjunctivitis were caused.

In order to solve these disadvantages, there is a chemical disinfection method in which a contact lens is immersed in a solution containing a disinfectant at room temperature as a method generally used in disinfection methods other than boiling.
As disinfectants used in such chemical disinfection methods, chlorhexidine, benzalkonium chloride, thimerosal, and the like have been proposed so far (see, for example, Patent Document 1, Patent Document 2, and Patent Document 3).

  However, they are often used at a certain high concentration in order to fully exhibit their disinfecting effect, and since these disinfectants have low molecular weights, they are adsorbed on contact lenses, particularly hydrous contact lenses. It has been reported that when it is easy to accumulate and a contact lens after disinfection is worn on the eye, there is a possibility that damage such as eye irritation or corneal damage may occur.

  Recently, for the purpose of solving these problems, an aqueous solution using a polymer of a biguanide compound (for example, see Patent Document 4) or an aqueous solution using a polymer of polyammonium chloride (for example, see Patent Document 5). Proposed.

A polymer having a particularly large molecular weight of the biguanide compound is said to be hardly adsorbed to a hydrous contact lens and hardly cause a problem causing eye damage. As a disinfecting preservation solution for contact lenses using a polymer of this biguanide compound, a product having a concentration of 0.00005 to 0.0001% by mass is sold in the United States.
In addition, a contact lens disinfectant preservation solution using ε-polylysine, which is an amino acid polymer naturally found in a polymer of L-lysine, as a bactericide has been proposed because of its extremely low toxicity to the human body. (For example, refer to Patent Document 6). It is known that ε-polylysine is used as a food additive and has a virus infection inhibitory effect and a phage growth inhibitory effect in addition to a microorganism growth inhibitory effect.
However, even if the contact lens disinfecting and preserving solution used in any of these methods is used in the formulation and composition described therein, it cannot be said that the sterilizing effect is sufficient. It did not have the effect of preventing microbial contamination.

For example, an aqueous solution in which a polymer of a biguanide compound is used in the formulation as described has a drawback that its disinfection effect is weak. In particular, it is pointed out that it is not effective against C. albicas and A. fumigus (see, for example, Patent Document 7).
In order to strengthen the disinfection effect in response to this indication, the content of the biguanide compound polymer, which is a disinfecting component, must be increased, and even if the polymer is difficult to be absorbed by contact lenses, the increase in the disinfecting component amount is in terms of safety. There is a limit. Furthermore, the degradability of the biguanide compound is not taken into consideration, and it is examined whether the low-molecular biguanide compound decomposed and released from the biguanide compound polymer, in other words, whether the biguanide group is safe for the eye tissue. The problem remains in its safety.
In addition, ε-polylysine alone cannot be said to have a sufficient disinfection effect, and is not suitable for the use of a contact lens disinfectant that is usually used with a sterilization time setting of 4 hours. The bactericidal efficacy is only confirmed by the bactericidal effect on the 7th and 14th.

Furthermore, a biguanide fungicide is used together with a nonionic tonicity agent such as glycerin or propylene glycol as a contact lens solution having an excellent bactericidal effect and safety for eyes (for example, patent documents) 8) and the use of ε-polylysine together with a nonionic tonicity agent and / or an amino acid (see, for example, Patent Document 9).
However, when used in the formulations and compositions described there, the sterilization efficacy has been improved, but in ionic high water content type hydrous contact lenses (Group IV lenses), the lenses become larger after disinfection and storage. The use of hydrous contact lenses was not considered.

  Similarly, a biguanide or quaternary ammonium salt fungicide is used together with an isotonic agent having low electrical conductivity and low concentrations of sodium chloride, phosphoric acid and salts thereof (for example, see Patent Document 10). It has been proposed to use a cationic polymer preservative together with a nonionic tonicity agent such as inositol and a low concentration of chloride (see, for example, Patent Document 11). However, it has only been evaluated for a specific microorganism, and has not been sufficiently evaluated for the use of hydrous contact lenses.

Further, a disinfecting preservation solution comprising polylysine and / or protamine and one amino acid among glycine, alanine, arginine and histidine is known (for example, see Patent Document 12).
However, this preservative solution does not have sufficient antibacterial properties and has not been evaluated for compatibility with hydrous contact lenses.

Japanese Patent Laid-Open No. 52-109953 Japanese Patent Laid-Open No. 62-153217 JP 63-59960 A JP-A-61-85301 JP-T58-501515 PCT International Publication No. WO 97/27879 Japanese Patent Laid-Open No. 4-231054 JP-A-10-108899 JP 2000-84052 A JP 2003-89601 A Special table 2004-512904 gazette JP 2001-264707 A

The present invention provides a disinfecting preservation solution for contact lenses that has a sufficient disinfecting effect, has extremely low eye toxicity, is considered to be used for hydrous contact lenses, and can be used safely. With the goal.
Therefore, in order to achieve this purpose, as a result of intensive research on various known natural polymers that are considered to have antibacterial and bactericidal activity, the use at a concentration below a certain level has low toxicity to the eye, and it is used for contact lenses. It has been found that the antibacterial (sterilizing) effect of ε-polylysine is dramatically increased by further containing an organic cation compound and lactic acid in ε-polylysine having sufficient safety for use as a disinfecting preservation solution.
Furthermore, by adding inositol or glycerin to the solution having such a composition, it is possible to further improve the antibacterial property, and in addition to this, during the alteration or disinfection of the lens during the cleaning of the hydrous contact lens (solution) The present inventors have found that it is possible to minimize the change with time of immersion) and have completed the present invention based on such knowledge.

That is, the present invention relates to a disinfecting preservation solution for contact lenses, characterized by containing ε-polylysine, an organic cation compound and lactic acid in an aqueous medium.
Furthermore, the present invention relates to a disinfecting preservation solution for contact lenses, characterized in that ε-polylysine, an organic cation compound, lactic acid and further inositol or glycerin are contained in an aqueous medium.

That is, the gist of the present invention is a contact lens disinfecting and preserving solution characterized in that a medicine is prepared by the above combination in order to solve the above-described problems.
The use of sodium salts such as sodium chloride and sodium phosphate, which are generally used as isotonic agents, reduces the antibacterial properties of ε-polylysine due to the influence of sodium ions. Therefore, the present inventors have eagerly searched for a component that suppresses deformation such as lens size change when washing hydrous contact lenses without suppressing the antibacterial properties of ε-polylysine. It turns out that there is. However, the antibacterial property is still insufficient by itself, and further investigations have shown that the use of lactic acid has proved effective, and further, the combined use of inositol or glycerin further increases the antibacterial property. Has been found to be possible.

The antiseptic preservative solution for contact lenses of the present invention can suppress the addition amount remarkably low by preparing an environment in which the antibacterial properties of ε-polylysine, which is an antibacterial (bactericidal) component, can be maximized. Further enhanced disinfection preservation solution.
Moreover, the contact lens disinfecting preservation solution of the present invention can easily disinfect contact lenses without using a boiling disinfecting instrument. Furthermore, for safety, it consists only of carefully selected highly safe ingredients, and even if it is immersed for a long time, there is no effect on the contact lens, and the need to worry about eye damage is removed, You can wear contact lenses after disinfection with confidence.

The disinfecting preservation solution for contact lenses of the present invention has a content of ε-polylysine in the solution, which varies depending on the amount of the organic cation compound to be contained, the amount of lactic acid and the pH of the solution, but is in the range of 0.00001 to 0.005% by mass. Is necessary.
In addition, the organic cation compound used in the present invention does not diminish the antibacterial and bactericidal effects of ε-polylysine, and is used for adjusting the osmotic pressure of the solution and adjusting the pH depending on the type of use, and suppressing swelling of the hydrous contact lens. Used for. As the organic cation compound that best exhibits such an effect, the use of basic amino acids such as lysine, arginine, histidine, tris (hydroxymethyl) aminomethane, methylglucamine (meglumine) or salts thereof is preferable. . Moreover, regarding this usage-amount, the range of 0.1-5.0 mass% is preferable. If the amount of the organic cation compound deviates from this range and is less than 0.1% by mass, it becomes difficult to suppress the swelling of the hydrous contact lens, and conversely, the use exceeds 5.0% by mass. When the amount is reached, the antibacterial properties of ε-polylysine are adversely affected.

In addition, lactic acid used in the present invention has an effect as an enhancement aid that enhances the antibacterial and bactericidal effects of ε-polylysine. This lactic acid has an action of enhancing the antibacterial effect particularly against S. aureus.
Regarding the type of lactic acid, any of D-form, L-form and DL-form can be used. The amount of lactic acid used should be in the range of 0.0005 to 3.0% by mass in the disinfecting and preserving solution. If the amount of lactic acid added deviates from this range and is less than 0.0005% by mass, the effect of using lactic acid is not exhibited. On the other hand, when the amount of lactic acid added exceeds 3.0% by mass, it is not desirable to use an excessive amount because the hydrous contact lens contracts.

  In the present invention, when it becomes necessary to use a sodium salt, the sodium ion concentration is made as low as possible and Na is less than 0.2% by mass. That is, when the sodium ion is 0.2% by mass or more, the antibacterial and bactericidal effects of ε-polylysine are significantly reduced.

  Next, inositol or glycerin used in the present invention can be expected to have a moisturizing action because it has many hydroxyl groups in its structure. The amount used is preferably in the range of 0.1 to 13.0% by mass. If the amount of use deviates from this range and becomes lower than this, there is no effect due to the addition of inositol or glycerin. On the other hand, even if the amount used exceeds this range, the antibacterial effect is not so high. In addition, a large amount of use is not preferable because it unnecessarily increases the osmotic pressure of the solution.

Furthermore, it is also important in the present invention that the contact lens disinfecting and preserving solution of the present invention exhibits the maximum effect by setting its solution pH to 6.0 to 8.0.
Moreover, the disinfecting preservation solution for contact lenses of the present invention can also use boric acid as a pH buffer. The amount used is preferably in the range of about 0.1 to 1% by mass.

Furthermore, the disinfecting and preserving solution for contact lenses of the present invention can further contain a surfactant in order to remove proteins and lipid components adhering to the contact lenses and improve the cleaning effect.
Examples of such surfactants include polyoxyethylene glycol alkyl phenyl ether, polyoxyethylene-polyoxypropylene condensate, alkyl polyoxyethylene ether, glycerin ester polyoxyethylene ether, sorbitan ester polyoxyethylene ether Nonionic surfactants such as polyethylene glycol fatty acid esters are preferred because of their low irritation to the ocular mucosa and the absence of effects such as incorporation into hydrous contact lenses.

  Furthermore, the disinfecting preservation solution for contact lenses of the present invention can use a thickener and a protein removing agent (proteolytic enzyme, etc.) as other additive components. Any of these components can be used as long as they are highly safe to living organisms and have no influence on adsorption to a contact lens. It can also be added in combination at a concentration and type that do not impair the action and effect of.

  The contact lens disinfecting and preserving solution of the present invention does not require any special method for preparing the same, and in the same manner as in the case of preparing a normal aqueous solution, each component is dissolved in a predetermined amount of purified water to obtain a uniform solution. After being dissolved in the solution, it is injected through a sterile filtration step into a container to be provided under aseptic conditions, and then sealed.

  The contact lens disinfecting and preserving solution of the present invention produced as described above is used as an example when the contact lens is cared for. The contact lens can be disinfected by immersing it in a storage case filled with the solution for a predetermined time, preferably about 30 minutes to 4 hours.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited only to these Examples. In the examples, “%” means “% by mass” unless otherwise specified.

[Examples 1 to 12]
Each drug was mixed and dissolved in the addition amount shown in Table 1 to prepare a disinfecting preservation solution for contact lenses. In addition, the chemical | medical agent used is as follows.
ε-Polylysine: manufactured by Chisso Corporation
L (+)-Arginine: Wako Pure Chemical Industries, Ltd. reagent grade glycerin: Wako Pure Chemical Industries, Ltd. reagent grade
L-lactic acid: Wako Pure Chemical Industries, Ltd. reagent special grade
myo-Inositol: Wako Pure Chemical Industries, Ltd. reagent grade
D (-)-N-methylglucamine: Merck
L (+)-Lysine: Special grade reagent manufactured by Wako Pure Chemical Industries, Ltd.
L-Histidine: Wako Pure Chemical Industries, Ltd. Reagent Special Tris (hydroxymethyl) aminomethane: Sigma Reagent Sodium Chloride: Wako Pure Chemical Industries, Ltd. Reagent Special Sodium Hydroxide: Wako Pure Chemical Industries, Ltd. Reagent special grade boric acid: Wako Pure Chemical Industries, Ltd. Reagent special grade hydrochloric acid: Wako Pure Chemical Industries, Ltd. Reagent special surfactant: Asahi Denka Kogyo Co., Ltd., Pluronic SE500
Thickener: Shin-Etsu Chemical Co., Ltd., Metroz 60SH-50
The pH of the solution was all adjusted using hydrochloric acid. Further, the dissolved and prepared solution was sterilized by using a 0.20 micron cellulose acetate filter (Millipore, Millex) and passing the solution through this filter.

[Comparative Examples 1-4]
For comparison, an antiseptic stock solution for contact lenses was prepared in the same manner as in the Examples at the ratio shown in Table 2.

<Sterilization test>
As test bacteria for sterilization tests, the bacteria are Pseudomonas aeruginosa (IFO13275), Staphylococcus aureus (IFO13276), Serratia marcecens (JCM1239), and Candida albi (Candida albicans: JCM2085) Fusarium solani (ATCC36031) was used, and the bacteria were cultured in soybean casein digest medium at 35 ° C for 18 hours. The solution became cloudy and a test bacterial solution of 10 ⁸ cfu / mL was prepared. On the other hand, Candida albicans was cultured on Sabouraud dextrose agar medium at 35 ° C for 18 hours, suspended in sterilized PBS (-), and prepared 10 ⁸ cfu / mL test solution. What was cultured on a potato dextrose agar medium at 25 ° C. for 1 week was suspended in 0.1% peptone saline to prepare a 10 ⁸ cfu / mL test bacterial solution.

Next, 20 mL of the sterilized disinfectant solution to be evaluated was placed in a sterilized medium bottle, 0.1 mL of the prepared test bacterial solution was further added, and then stored in a thermostat at 25 ° C. for 4 hours. After storage, the bottle was taken out and a predetermined amount of the solution was diluted with sterilized PBS (−), and then the viable cell count in 1 mL of the sample was measured by the pour plate method. The culture conditions in this pour plate method were as follows: bacteria were cultured in soybean casein agar medium supplemented with lecithin / polysorbate 80 at 35 ° C. for 48 hours, and Candida albicans was cultured with potato dextrose supplemented with lecithin / polysorbate 80. Culturing was carried out on an agar medium at 35 ° C. for 48 hours, and Fusarium solani was cultured on a potato dextrose agar medium supplemented with lecithin / polysorbate 80 at 25 ° C. for 5 days.
From the number of viable bacteria obtained by measuring the number of bacteria after culture, after calculating the number of viable bacteria after the specified time of the contact lens disinfection preservation solution to which the test bacterial solution was added, according to the following formula: The bacterial reduction amount converted to logarithm was calculated.

Bacterial reduction [logarithmic conversion] = Log (viable count in 1 mL of bacterial suspension immediately after preparation) −Log (viable count in 1 mL of bacterial suspension after 4 hours treatment)
About Examples 1-12 and Comparative Examples 1-5, the disinfection effectiveness with respect to 2-5 types of test bacteria was investigated. The results are shown in Table 3.

  As is clear from the results in Table 3, all the examples showed high disinfection effectiveness. It can also be seen that the addition of inositol or glycerin increases the antibacterial effect against Serratia marcescens.

<Changes in dimensions of hydrous contact lenses>
The change of the dimension of the hydrous contact lens of the disinfecting preservation solution for contact lenses of the present invention was tested. The hydrous contact lens used in the test is a one-day accumulator (base curve 9.00 mm, diameter 14.200 mm) manufactured by Johnson & Johnson Co., Ltd., which is classified into a highly hydrous, ionic group IV.
A hydrous contact lens was immersed in the antiseptic storage solutions of the present invention and comparative examples, and the lens diameter was measured after 5 minutes and 2 weeks.
The results are shown in Table 4.
As is clear from the results in Table 4, it can be seen that the disinfecting and preserving solution for contact lenses of the present invention has a small swelling and shrinkage of the lens and is in a range without any problems. In comparison with this, it can be seen that the solution of Comparative Example 3 swells significantly after 5 minutes of immersion and has poor lens compatibility.

Claims (5)

An antiseptic storage solution for contact lenses, comprising ε-polylysine, an organic cation compound and lactic acid in an aqueous medium. The disinfecting preservation solution for contact lenses according to claim 1, wherein the organic cationic compound is one or more compounds of lysine, arginine, histidine, tris (hydroxymethyl) aminomethane, methylglucamine or a salt thereof. An antiseptic storage solution for contact lenses, comprising ε-polylysine, an organic cation compound, and lactic acid in an aqueous medium, and further inositol or glycerin. The antiseptic storage solution for contact lenses according to claim 3, wherein the organic cation compound is one or more compounds of lysine, arginine, histidine, tris (hydroxymethyl) aminomethane, methylglucamine or a salt thereof. The disinfecting preservation solution for contact lenses according to any one of claims 1 to 4, wherein the disinfecting preservation solution for contact lenses is for a hydrous contact lens.