JP2002143277A - Anti-acanthamoeba disinfection preservative for contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an anti-acanthamoeba disinfection preservative for a contact lens except a group 4 lens and to provide a method for simply, efficiently and safely disinfecting and preserving by using the same. SOLUTION: The method using the anti-acanthamoeba disinfection preservative for the contact lens containing an effective amount of a polylysine comprises the step of dipping the contact lens (except the group 4 lens) removed from an eye in the anti-acanthamoeba disinfection preservative to simply and safely disinfect the lens against the acanthamoeba containing an acanthamoeba at a cystic period. After the disinfection, the lens can be worn in the eye as it is, but the lens can be worn in the eye after the lens is rinsed with the anti- acanthamoeba disinfection preservative, a physiological saline or a rinsing liquid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a disinfectant / antiseptic agent for contact lenses containing an effective amount of polylysine, which is an anti-acantomomeba, comprising a high water content / ionic water content soft contact lens (group 4 lens). The present invention relates to an anti-Acanthamoeba disinfectant / preservative for contact lenses, which is applied to contact lenses other than the above). In particular, the present invention relates to an anti-Acanthamoeba disinfectant / preservative for contact lenses other than Group 4 lenses, which has a disinfecting effect on Acanthamoeba in the cyst stage. Furthermore, the present invention relates to a method for disinfecting and preserving contact lenses other than the group 4 lens using the above-mentioned anti-acantomomeba disinfectant / preservative for contact lenses.

[0002]

2. Description of the Related Art Acanthamoeba, a kind of protozoa, is a ubiquitous free-living amoebae.
It is called c) and is present throughout the environment, for example, in freshwater, seawater, soil, air and the like. This Acanthamoeba has two forms, trophozoite and cyst. Former trophoz
Oite is characterized by its habit of eating the bacteria present in the environment and multiplying in two divisions, is highly sensitive to drugs, and is relatively easy to disinfect. However, in an environment where it is difficult for them to live, such as environmental degradation and depletion of food sources, the cyst changes to the latter cyst, which has a double wall and is very resistant. It is said that it is very difficult to disinfect this cyst acanthamoeba.

[0003] Normally, the infectivity of Acanthamoeba is said to be very low, and the probability of transmission to healthy individuals is said to be very low. However, Acanthamoeba keratitis often seen in contact lens wearers as an example of infection Is mentioned. Acanthamoeba keratitis has been frequently reported among contact lens wearers, particularly among those who wear water-containing soft contact lenses. Previously, it was reported mainly in Europe and the United States that tended to care for hydrated soft contact lenses using a treatment solution using tap water, but recently, cases of infection with Acanthamoeba have increased in Japan, At worst, it can lead to blindness. However, no effective means for disinfecting Acanthamoeba that occurs during wearing of a contact lens is known.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide an anti-acanthamoeba disinfectant / preservative for contact lenses that is effective for contact lenses other than highly water-containing and ionic water-containing soft contact lenses (group 4 lenses). Is to do. It is still another object of the present invention to provide a method for disinfecting and preserving a contact lens using the anti-acantomomeba disinfecting and preserving agent for a contact lens.

[0005]

According to the present invention, the above objects and advantages of the present invention are achieved by the following. (1) An anti-Acanthamoeba antiseptic / preservative for contact lenses other than highly water-containing and ionic water-containing soft contact lenses (group 4 lenses), comprising an effective amount of polylysine. (2) The concentration of polylysine is 0.0001 to 2 (w / v)
%, Wherein the anti-acantomoeba disinfectant / preservative for contact lenses according to (1) above is used. (3) The anti-Acanthamoeba antiseptic / preservative according to the above (1) or (2), wherein the polylysine is ε-polylysine. (4) The anti-Acanthamoeba disinfectant / preservative for contact lenses according to any of (1) to (3), further comprising a disinfectant. (5) The anti-acantomoeba disinfectant / preservative for contact lenses according to the above (4), which contains any one or more of polyhexamethylene biguanide and / or a salt thereof and a quaternary ammonium salt as a disinfectant. . (6) The above-mentioned (1), wherein the acanthamoeba to be disinfected is a cyst-stage acanthamoeba.
The anti-Acant amoeba disinfectant / preservative for contact lenses according to any one of (1) to (5). (7) The above (1), further comprising tris (hydroxymethyl) aminomethane, boric acid and / or a salt thereof, a metal chelating agent and a surfactant.
The anti-Acant amoeba disinfectant / preservative for contact lenses according to any one of (6) to (6). (8) A contact lens other than a highly water-containing and ionic water-containing soft contact lens (group 4 lens) is used as the anti-acantomomeba disinfectant / preservative for contact lenses according to any one of the above (1) to (7). A method of preserving while immersing and disinfecting Acanthamoeba.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The anti-Acanthamoeba disinfectant / preservative for contact lenses of the present invention uses polylysine as a disinfecting component for Acanthamoeba. More preferably, the polylysine is ε-polylysine.
The amount of polylysine is 0.0001 to 2 (w
/ V)%. The preferred concentration range is 0.
001 to 1 (w / v)%, more preferably 0.0
The concentration range is 1 to 0.5 (w / v)%.

[0007] Polylysine is a polymer of L-lysine, which is an amino acid, and is found in a species of actinomycetes in soil, and binds to viruses, bacteria, and the like by electrostatic and hydrophobic interactions. It is known to inhibit activity. At present, it is widely used as a food additive and preservative in cooked rice and prepared foods. Japanese Patent Publication No. 8-504346 discloses that polylysine significantly reduces the formation of protein deposits on and / or in a hydrophilic contact lens.
/ 27879 reports the use of polylysine as a solution for the preservation and disinfection of contact lenses.
Furthermore, JP-A-2000-84052 reports a liquid preparation for contact lenses containing an amino acid and / or a nonionic tonicity agent together with polylysine.

[0008] This polylysine is disclosed in JP-T-8-5043.
As disclosed in No. 46, contact lenses,
In particular, it may be adsorbed to a highly hydrated and ionic lens belonging to Group 4 among the hydrous soft contact lenses (referred to as “Group 4 lens” in the present invention).
As a result of intensive studies conducted by the present inventors, when a group 4 lens was repeatedly treated using a solution containing polylysine, polylysine was adsorbed and accumulated on the group 4 lens, and the lens on which polylysine was adsorbed and accumulated was attached to the eye. At that time, it was found that eye irritation might be given. Therefore, in the present invention, these group 4 lenses are not applicable.

In the present invention, in addition to polylysine as an Acanthamoeba disinfectant, a drug generally used as a disinfectant can be blended. Examples of the agent include polyhexamethylene biguanide, polyquaternary ammonium salts, chlorohexidine, iodine-based disinfectants such as povidone iodine or polyvinyl alcohol iodine, ethanol, alcohols such as isopropyl alcohol,
And N-alkyl-2-pyrrolidones in which the alkyl group is octyl or dodecyl. Among them, polyhexamethylene biguanide or polyquaternary ammonium salt is preferred. Further, the polyhexamethylene biguanide preferably has a polymerization degree range of n = 1 to 500 and a molecular weight range of about 200 to about 100,000, and the quaternary ammonium salt is Cosmetic, To.
iletry, andFragrance Assoc
Polyquater by the name of the Iation (CTFA)
sodium-1,2,6,7,10,11,16,22 and 28, and a molecular weight range of about 200 to about 1,0.
Preferably, it is 00,000. When an iodine-based disinfectant is used, a neutralization operation using, for example, a sulfur-containing reducing agent or the like is separately required. The amount of these disinfectants is determined appropriately according to the concentration of polylysine, but the concentration range to be incorporated in the preparation is 0.01 to 10,000 ppm.
, Preferably 0.1 to 100 ppm, more preferably 0.5 to 10 ppm.

[0010] The anti-Acanthamoeba antiseptic / preservative for contact lenses of the present invention may further contain a buffer. Preferred examples of the buffer include tris (hydroxymethyl) aminomethane and a combination of boric acid and / or a salt thereof, and other boric acid-based buffers, acetic acid-based buffers used as ordinary buffers, It is also possible to use a citrate buffer or the like. The concentration of tris (hydroxymethyl) aminomethane in the preparation is 0.05 to 2 (w / v)%, preferably 0.1%.
1 to 1.2 (w / v)%, more preferably 0.2 to 0.
6 (w / v)%. The concentration of boric acid and / or a salt thereof in the preparation is 0.01 to 2.5 (w / v)%,
Preferably it is 0.05-2.5 (w / v)%, more preferably 0.1-1.5 (w / v)%.

Further, a metal chelating agent may be further contained. In addition to its purpose as a metal chelator,
When used in combination with a disinfectant, the disinfecting effect can be more synergistically provided. Examples of the metal chelating agent include polycarboxylic acids and / or salts thereof. Among them, disodium ethylenediaminetetraacetate (E
DTA.2Na) is particularly preferred. The concentration of the metal chelating agent in the formulation is usually 0.01 to 1
(W / v)% is preferred.

Further, if necessary, a surfactant may be contained. Specifically, a cationic surfactant, an amphoteric surfactant, a nonionic surfactant and an anionic surfactant are used. Examples of the cationic surfactant include tri (polyoxyethylene) stearyl ammonium chloride (5EO), oleylbis (2-hydroxyethyl) methylammonium chloride, lanolin fatty acid aminopropylethyldimethylammonium ethosulfate and N- Cocoyl-L-arginine ethyl ester-
DL-pyrrolidone carboxylate and the like. Examples of amphoteric surfactants include sodium lauryl diaminoethyl glycine, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine and alkyldimethylamine oxide.
Examples of nonionic surfactants include polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene sorbitan alkyl ester, polyoxyethylene hydrogenated castor oil,
Examples include fatty acid monoglycerides, propylene glycol fatty acid esters, fatty acid sucrose esters, polyoxyethylene-polyoxypropylene ethylene diamine condensates, and the like. Examples of anionic surfactants include α
Olefin sulfonates, alkyl sulfonates, alkyl benzene sulfonates, carboxylated ether salts having a polyoxyethylene chain, alkyl phosphates, alkyl ether phosphates / sulfates having a polyoxyethylene chain, alkyl sulfates , Alkyl sulfate ethers, alkyl sarcosine salts, alkyloyl methyl taurine, alkyloyl benzalcosine and the like. These may be used alone or in the formulation together with one or more of the surfactants listed above, but when using anionic surfactants, polylysine and / or other disinfectants may be used. The effect when used in combination with the agent is checked beforehand and the combination is selected. The concentration in the formulation is usually 1 × 1
^{0 -5 ~1 (w / v)} % are preferred. As for the purpose of compounding the surfactant, when used as a care product for contact lenses, it is effective for removing fat stains and the like adhering to the contact lens, so that the surfactant can be compounded as necessary. Also, some types of amphoteric surfactants contribute to enhancement of the disinfecting effect.

[0013] In addition to the above-mentioned components, the anti-acantomomeba disinfectant / preservative for contact lenses of the present invention further comprises:
At least one tonicity agent selected from the group of sodium chloride, potassium chloride, potassium iodide, glycerin, propylene glycol, polyethylene glycol, mannitol, sorbitol, dextrin, and dextran; and selected from the group of glycine, lysine, and glutamic acid. At least one kind of a thickener selected from the group consisting of at least one kind of amino acids, cellulose and / or derivatives thereof, chitosan and / or derivatives thereof, polyvinylpyrrolidone and polyvinyl alcohol, hyaluronic acid and salts thereof, chondroitin sulfate and salts thereof; It can also be contained. In addition, urea and / or a derivative thereof can be appropriately compounded.

Further, the anti-acantomoeba disinfecting / preserving agent for contact lenses of the present invention preferably has a pH in the range of 5.5 to 8.0, more preferably 6.5 to 8.0 when prepared as a solution. 0.0, particularly preferably 7.0 to 7.5. The osmotic pressure is 180 to 10,000
mOsm. Is determined as appropriate, but the osmotic pressure at the time of contacting the contact lens is 180 to 460 mOsm.
And more preferably 26
0-360 mOsm. 290-310 mOsm.
It is preferred that

Among the above liquid preparations, ε-polylysine is 0.01 to 0.5 (w / v)%, polyhexamethylene biguanide is 0.5 to 10 ppm, and the buffer is 0.3 to 0.3%.
2.1 (w / v)%, and further 0.01 to 0.01% of the chelating agent
1 (w / v)%, and further, a surfactant is added in an amount of 1 × 10 ⁻⁵ to 1
(W / v)% is particularly preferable because it has the advantages of excellent anti-acanthamoeba disinfection and preservation effects of contact lenses, and also has the advantage of disinfecting fungi in addition to acanthamoeba.

The anti-acantomoeba disinfecting / preserving agent for contact lenses of the present invention is preferably in the form of a liquid. The above components are dissolved in water sequentially, the volume is adjusted with water, and finally the acid or acid is added. By adjusting the pH with an alkali, it can be industrially advantageously produced. When dissolving, 5 to 15 (w /
v)% aqueous solution of polyhexamethylene biguanide
A 30% (w / v)% solution is prepared, and these are blended at a predetermined ratio, whereby the preparation becomes easier. In addition, a non-liquid type may be used depending on the type of the object to be disinfected.

The anti-Acanthamoeba disinfection according to the present invention
As a method of using the preservative, for example, the target contact lens may be added to a solution in which the above-mentioned liquid or non-liquid type is dissolved in a water-soluble anti-Acanthamoeba disinfectant / preservative.
Disinfection is performed by immersion for 0 minutes or more, preferably for 20 minutes or more. After sufficient disinfection, it may be attached to the eye as it is, or may be attached to the eye after rinsing the contact lens with the anti-Acanthamoeba disinfecting / preservative, physiological saline or a rinsing solution. If there is a protein or fat stain, the lens may be rubbed in advance with the anti-Acanthamoeba disinfectant / preservative before starting disinfection. When attaching the lens, if an iodine-based disinfectant is added as an additional disinfectant to the above solution, it is necessary to separately perform a neutralization operation using, for example, a sulfur-containing reducing agent after disinfection. Become.

The contact lenses to be disinfected in the present invention include water-containing soft contact lenses (except for group 4 lenses) that need to be disinfected on a daily basis, and hardware that has been confirmed to have Acanthamoeba infection. Examples include contact lenses and non-hydrous soft contact lenses. Furthermore, when various surfactants and the like are contained in the anti-acantomoeba disinfecting / preserving agent for the contact lens of the present invention, the contact lens is rubbed with the preparation or immersed in the preparation for a certain period of time. The lens can be cleaned and at the same time provide a disinfection effect. When the preparation is diluted with a contact lens diluent and used, the lens is immersed for cleaning, and at the same time, Acanthamoeba can be disinfected. Furthermore, after treating the contact lens with a commercially available ordinary care system, the lens is rinsed with the anti-Acanthamoeba disinfectant / preservative for contact lenses of the present invention immediately before being attached to the eye, and the lens is rinsed. Can be attached to the eye in a cleaner state.

[0019]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited thereto.

Example 1 Solutions 1 to 6 and comparative solutions 1 and 2 were prepared so that the total amount of the components shown in Table 1 was 100 mL. In Table 1, EDTA · 2Na is an abbreviation for ethylenediaminetetraacetic acid · disodium, and PHMB is an abbreviation for polyhexamethylene biguanide.

[0021]

[Table 1]

In the above preparation, the following experimental materials were prepared. The MY medium is Malt extra
0.1 g of ct medium and 0.1 g of Yeast extract medium were dissolved and dissolved in 1 L of distilled water, and autoclaved at 121 ° C. for 20 minutes. Physiological saline for Acanthamoeba (hereinafter referred to as Amoeba raw food) is 12.0 g of sodium chloride, 0.35 g of potassium chloride, 0.30 g of calcium chloride, and magnesium sulfate (heptahydrate).
0.40 g and 6.0 g of tris (hydroxymethyl) aminomethane were dissolved in 1 L of distilled water, adjusted to pH 6.8, further diluted 100 times and autoclaved at 121 ° C. for 20 minutes. EC (Escher) for culturing Acanthamoeba after disinfection test
ichia coli) MY plate was prepared by the following procedure. First, EC (ATCC8739) was cultured overnight in a soybean casein digest medium. Next, sterilize the EC culture solution 0.1m in 500mL of MY medium.
L was added, and 1.5 mL was dispensed into a 12-well multiwell plate with sufficient stirring to prepare. The neutralizing solution used to stop the reaction of the sterilizing and disinfecting components was 0.7 (w / v)% lecithin and 0.1% polysorbate 80.
5% (w / v)% and mixed with raw food for amoeba,
It was prepared by stirring to form a suspension, and autoclaved at 121 ° C. for 20 minutes.

Acanthamoeba is Acantham
oeba castellanii (ATCC 3086)
Using 8), this strain was cultured according to the ATCC culture method.
Next, Acanthamoeba in the cyst phase was obtained from 102 plates cultured for 4 weeks or more according to the ATCC culture method.
It was collected using an appropriate amount of raw food for amoeba. The collected product is washed and replaced by centrifugation at 2,000 × g for 50 minutes using a saline for amoeba, and adjusted to a concentration of 1 × 10 ⁵ to 10 ⁶ cells / mL using a hemocytometer. did. This was used as an amoeba inoculum and stored at 4 ° C. or lower.

Next, for each of the above samples, cyst
Effect of Acanthamoeba during the period of disinfection was examined. That is, 80 μL of the inoculum was added to 8 mL of the prepared sample, and 0.1 μm from the mixed solution 4 hours after the time of addition of the inoculum.
L and 0.9 for neutralization of disinfecting and disinfecting components
The reaction was stopped by mixing with a neutralizing solution (mL) and allowing the mixture to stand for at least 10 minutes. Thereafter, 0.1 m of the liquid in which each reaction was stopped
L was mixed with 0.9 mL of an amoeboid diet, and a 10-fold diluted solution was prepared sequentially. 0.1 mL (n = 4) of each diluent was added to E
Each was added to the wells of the C-added MY plate. The plate was cultured at 25 ° C for 14 days, and the survival and growth of Acanthamoeba were observed using an inverted microscope.
The number of surviving cyst acanthamoeba was calculated according to the Muench calculation method. Table 2 shows the results of the disinfection effect of Acanthamoeba in the cyst phase after disinfection for 4 hours.

[0025]

[Table 2]

From the above results, it was found that the liquid preparation containing ε-polylysine showed a sufficient bactericidal effect even on cyst-stage Acanthamoeba. As a tendency, there was a concentration dependency on the blending amount of ε-polylysine. Also,
A similar experiment was carried out using a Bueno I (manufactured by Offtex) belonging to Group 1 of the hydrous soft contact lens, and the same result as above was shown.

Next, the formulation stability of the solution 1 was examined.
That is, ε-polylysine which is an active ingredient in the solution 1,
Polyhexamethylene biguanide formulated as an additional disinfectant, solution 4 for 4 points of osmotic pressure and pH
It was stored for 3 weeks at 2 ° C. and a relative humidity of 75%, and examined for any change. As a result, it was found that there was almost no change before and after storage, and that the preparation exhibited good stability.

Further, using the solution 3 shown in Table 1, the disinfection effect on fungi was also examined. Table 3 shows the results of the disinfection effect 4 hours after the addition of each bacterium. For the tests, the bacteria were S. aureus, P. aeruginosa.
uginosa), E. coli and S. marcescens, and fungi were performed using yeast (C. albicans).

[0029]

[Table 3]

[0030] As shown in Table 3, it was found that the composition of the present invention exhibited an excellent disinfecting effect not only on Acanthamoeba in the cyst stage but also on each bacterium.

[0031]

EFFECT OF THE INVENTION The present invention provides a simple and safe method of attaching to a contact lens (except for a group 4 lens) by using an anti-Acanthamoeba antiseptic / preservative for contact lenses containing an effective amount of polylysine. Acanthamoeba can be disinfected. Furthermore, it is possible to easily and safely disinfect Acanthamoeba in the cyst stage, which is said to be extremely difficult to disinfect. Further, not only Acanthamoeba but also fungi used in a normal storage effect test can be easily and safely disinfected.

 ──────────────────────────────────────────────────の Continued on the front page (72) Inventor Fumio Saito 156-5 Kamimidai, Toyooka-shi, Hyogo F-term in Offex Research Institute, Inc. (Reference) 2H006 DA08 4C058 AA09 BB07 JJ08 4H011 AA01 BA01 BA05 BB11 BC04 BC06 BC18 BC19 DA13 DD07 DH11

Claims (8)

[Claims] 1. A disinfectant / preservative for anti-Acanthamoeba for contact lenses other than highly water-containing and ionic water-containing soft contact lenses (group 4 lenses), comprising an effective amount of polylysine. 2. The polylysine concentration of 0.0001 to 2
(W / v)%. The anti-acantomomeba disinfecting / preserving agent for contact lenses according to claim 1, wherein 3. The disinfectant / preservative according to claim 1, wherein the polylysine is ε-polylysine. 4. The disinfecting / preserving agent for anti-acantomomeba for contact lenses according to claim 1, further comprising a disinfecting agent. 5. The anti-acant amoeba disinfection and storage for contact lenses according to claim 4, wherein the disinfectant contains at least one of polyhexamethylene biguanide and / or a salt thereof and a quaternary ammonium salt. Agent. 6. The acanthamoeba to be disinfected is c.
The anti-acanthamoeba disinfectant / preservative for contact lenses according to any one of claims 1 to 5, which is an acanthamoeba in the yst stage. 7. The method according to claim 1, further comprising tris (hydroxymethyl) aminomethane, boric acid and / or a salt thereof, a metal chelating agent and a surfactant. Anti-Acanthamoeba disinfectant and preservative for contact lenses. 8. A contact lens other than a highly water-containing and ionic water-containing soft contact lens (group 4 lens), wherein the anti-acanthomeba disinfectant / preservative for contact lenses according to any one of claims 1 to 7 is used. A method of immersing and preserving while disinfecting Acanthamoeba.