JP6148941B2 - Disinfecting composition containing phosphorylated oligosaccharide compound - Google Patents

Description

The present invention relates to a disinfecting composition and a contact lens solvent containing the disinfecting composition.

When the contact lens is worn on the eye, dirt of proteins and lipids derived from tears and eye grease adheres to the contact lens surface. These stains may cause bacteria to propagate and lead to eye diseases, and may cause problems such as a decrease in wearing feeling of contact lenses and an effect on eyesight correction.

Contact lenses are generally roughly classified into hard contact lenses and soft contact lenses. Among these, soft contact lenses tend to propagate microorganisms in the water in the contact lenses, so soft contact lenses with insufficient care may cause serious problems to eye tissues.

Therefore, in order to use the soft contact lens safely and hygienically, it is desirable that the contact lens be sufficiently cared for, for example, cleaned, disinfected, and maintained clean.

The process of caring for such contact lenses usually involves “cleaning” to remove dirt and the like adhering to the contact lens surface; “disinfection” to detoxify microorganisms; “rinsing” after cleaning and disinfection; and contact lens performance Including "save" to maintain. 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. An organic nitrogen-based disinfectant is widely used as a disinfecting component at this time.

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, high concentration disinfecting components are toxic to ocular tissues and thus have safety issues. Therefore, the blending amount (concentration) of the disinfecting component is limited and 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.

Therefore, in order to enhance the disinfection effect on soft contact lenses, a disinfecting composition comprising polyhexamethylene biquanide, which is a kind of organic nitrogen-based disinfectant, and a high concentration nonionic tonicity agent (patent) Reference 1) and disinfecting compositions (see Patent Document 2) containing polyhexamethylene biguanide and glycine are disclosed.

Japanese Patent No. 3698832 JP 2011-064723 A

The disinfecting composition of Patent Document 1 contains a polyhydric alcohol such as glycerin or propylene glycol at a high concentration as a nonionic tonicity agent. When a soft contact lens is processed using a liquid composition containing a high concentration of polyhydric alcohol, the contact lens may swell or deform, and the optical characteristics of the processed contact lens may be greatly affected. is there.

As shown in the Examples of Patent Document 2, the disinfecting composition of Patent Document 2 has a cell survival rate of 50% or less in the cytotoxicity test, and thus is not safe for ocular tissues. It is enough.

Therefore, when the disinfecting composition described in Patent Documents 1 and 2 is applied to a contact lens solvent, there are problems regarding adverse effects on the shape of the contact lens, disinfection effects, and / or safety to the eye tissue.

Therefore, in view of the above problems, the object of the present invention is to reduce the adverse effect on the shape of the contact lens compared to the prior art, satisfy the disinfection effect against bacteria and fungi, and is safe to the eye tissue. An object of the present invention is to provide a disinfecting composition applicable as a solvent for contact lenses.

In consideration of safety to eye tissues, the present inventors have conducted research and development on what has a disinfecting effect on contact lenses without increasing the amount of organic nitrogen-based disinfectant as an antiseptic component. Proceeded. And while intensively examining the improvement of the disinfection effect by the combination of the organic nitrogen-based disinfectant and other compounds, the inventors came to focus on phosphorylated oligosaccharide compounds.

Phosphorylated oligosaccharide calcium, which is a type of phosphorylated oligosaccharide compound, has a high safety such as having a demineralizing effect on teeth and a remineralizing effect on initial caries, and used as a cosmetic or food ingredient. It is known to be a compound.

However, at the same time, it is generally known that phosphorylated oligosaccharide compounds do not have a disinfecting effect, as shown by having high safety.

Surprisingly, however, the present inventors set the blending amount of the organic nitrogen-based disinfectant within the applicable range as a solvent for contact lenses by blending the organic nitrogen-based disinfectant and the phosphorylated oligosaccharide compound. Even so, we obtained a completely new finding that the disinfecting effect on microorganisms such as bacteria and fungi can be remarkably improved while maintaining safety to the eye tissue. The present invention has been completed based on such findings.

Therefore, according to the present invention, a disinfecting composition comprising an effective amount of an organic nitrogen-based disinfectant and a phosphorylated oligosaccharide compound is provided.

Preferably, the organic nitrogen disinfectant is a biguanide disinfectant or a quaternary ammonium disinfectant.

Preferably, the organic nitrogen-based disinfectant is polyhexamethylene biguanide, benzalkonium chloride or benzethonium chloride.

Preferably, the concentration of the organic nitrogen-based disinfectant is 0.0001 to 1.0 W / V%, and the concentration of the phosphorylated oligosaccharide compound is 0.0001 to 1.0 W / V%.

Preferably, the phosphorylated oligosaccharide compound is phosphorylated oligosaccharide calcium, phosphorylated oligosaccharide sodium, phosphorylated oligosaccharide magnesium or phosphorylated oligosaccharide potassium.

According to another aspect of the present invention, there is provided a contact lens solvent comprising the disinfecting composition of the present invention.

The disinfecting composition of the present invention is a disinfectant suitable as a solvent for contact lenses by combining an organic nitrogen-based disinfectant and a phosphorylated oligosaccharide compound in an amount within the range of application to a multipurpose solution. While having an effect, it has high safety to the eye tissue.

The contact lens treated with the contact lens solvent of the present invention containing the disinfecting composition of the present invention can keep its surface clean. Furthermore, the solvent for contact lenses of the present invention has a risk of eye damage caused by microorganisms adhering to the contact lens, a decrease in wearing feeling of the contact lens caused by dirt derived from eye grease and tears, and the dirt on the contact lens. It is possible to avoid an eye disorder caused by accumulation and an obstacle related to visual acuity correction.

Details of the present invention will be described below.
The disinfecting composition of the present invention contains an effective amount of an organic nitrogen-based disinfectant and a phosphorylated oligosaccharide compound. The principle of the disinfecting action of the disinfecting composition of the present invention is not particularly limited. For example, it can be assumed that the disinfecting effect of the organic nitrogen-based disinfectant as a disinfecting component is enhanced by the phosphorylated oligosaccharide compound.

The organic nitrogen-based disinfectant is not particularly limited as long as it is an organic compound containing a nitrogen atom and exhibits disinfection against microorganisms such as bacteria and fungi. For example, polyhexamethylene biguanide, polyamino Biguanide disinfectants such as propylbiguanide; quaternary ammonium disinfectants such as benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride. In the present invention, polyhexamethylene biguanide is preferred as the biguanide disinfectant, and benzalkonium chloride and benzethonium chloride are preferred as the quaternary ammonium salt compound. The organic nitrogen-based disinfectant may be a single disinfectant or a combination of two or more disinfectants.

The phosphorylated oligosaccharide compound used in the present invention is not particularly limited as long as it is a compound having a phosphate group or a phosphate group in the side chain of the oligosaccharide. For example, phosphorylated oligosaccharide calcium, phosphorylated oligosaccharide Phosphorylated oligosaccharide metals such as sugar potassium, phosphorylated oligosaccharide sodium, phosphorylated oligosaccharide magnesium and the like may be mentioned, any one of these may be used alone, or a combination of two or more may be used. As the phosphorylated oligosaccharide compound in the present invention, phosphorylated oligosaccharide calcium is preferable.

When phosphorylated oligosaccharide calcium is selected as the phosphorylated oligosaccharide compound, it is expected, without limitation, that the disinfecting composition of the present invention has a favorable effect on the ocular tissue. For example, by wearing a contact lens that has been sterilized using the disinfecting composition of the present invention, calcium in the composition may be dissolved in tears and applied to the eye tissue. Since calcium usually affects muscle contraction, wearing a contact lens sterilized using the disinfecting composition of the present invention, ciliary muscles, extraocular muscles, etc. involved in the movement of the lens and eyeball, etc. There is a possibility that the contraction effect of the eye muscle tissue of the eye is improved.

The method for obtaining the phosphorylated oligosaccharide compound is not particularly limited, and a commercially available product may be purchased. A document that discloses a method for producing a phosphorylated oligosaccharide compound, for example, a feature that discloses a method for producing an oligosaccharide. JP 2007-314585; JP 2006-249316 A which discloses a method for producing a long-chain phosphorylated oligosaccharide; JP-A 10-084985 which discloses a method for producing a short-chain phosphorylated oligosaccharide; A method known by those skilled in the art may be applied by referring to the description in JP-A No. 2002-145893 that discloses a method for producing an oxidized oligosaccharide metal.

The composition ratio of the disinfecting composition of the present invention is not particularly limited as long as it contains an effective amount of an organic nitrogen-based disinfectant and a phosphorylated oligosaccharide compound. The “effective amount” in the present invention refers to the amount (concentration) of the organic nitrogen-based disinfectant and phosphorylated oligosaccharide compound that can achieve the object of the present invention. That is, the concentration of the organic nitrogen-based disinfectant and the phosphorylated oligosaccharide compound in the disinfecting composition of the present invention is a concentration at which contact lens shape stability, safety to eye tissues, and disinfection effects against bacteria and fungi are observed. If it is, it will not be specifically limited.

The compounding amount (concentration) of the organic nitrogen-based disinfectant is not particularly limited as long as it is within the range used in ordinary contact lens solvents. For example, when disinfection is taken into account, a biguanide such as polyhexamethylene biguanide is used. In the disinfectant, 0.00005 W / V% or more is preferable, and 0.00009 W / V% or more is more preferable. In consideration of safety such as eye irritation, 0.0002 W / V% or less is preferable, and 0.00015 W / V% or less is more preferable.

When the organic nitrogen-based disinfectant is a quaternary ammonium-based disinfectant such as benzalkonium chloride or benzethonium chloride, the concentration is preferably 0.0005 W / V% or more in consideration of disinfection, for example, 0 0.001 W / V% or more is more preferable. In consideration of safety such as eye irritation, 0.05 W / V% or less is preferable, and 0.015 W / V% or less is more preferable.

Since the phosphorylated oligosaccharide compound originally has little influence on the human body such as ocular tissue, the upper limit of the amount (concentration) of the phosphorylated oligosaccharide compound in the present invention is not particularly limited. The amount of the phosphorylated oligosaccharide compound of the present invention may be an amount that can solve the object of the present invention in consideration of the amount of the organic nitrogen-based disinfectant to be blended together. For example, when the concentration of the organic nitrogen-based disinfectant is 0.0001 to 1.0 W / V%, the concentration of the phosphorylated oligosaccharide compound is preferably 0.0001 to 1.0 W / V%, 0.001 to 0 .1 W / V% is more preferable, and 0.005 to 0.05 W / V% is more preferable. The disinfecting composition of the present invention is characterized by having an enhanced disinfecting effect against microorganisms including bacteria and fungi, while having a disinfecting component blending amount comparable to that of a conventional contact lens cleaner.

However, if the amount of the phosphorylated oligosaccharide compound is too small, for example, less than 0.0001 W / V%, the disinfecting composition of the present invention may not be able to exhibit an enhanced disinfecting effect. In addition, when the amount of the phosphorylated oligosaccharide compound exceeds 1.0 W / V%, since the microorganism may grow using the phosphorylated oligosaccharide compound as a nutrient source, the disinfecting effect of the disinfecting component is suppressed. Not desirable.

The form of the disinfecting composition of the present invention is not particularly limited, and may be any of solid, liquid, semi-solid such as gel, and the shape of the object to which the disinfecting composition of the present invention is applied. It may be determined appropriately according to the situation. The method of using the disinfecting composition of the present invention is not particularly limited, and the disinfecting composition of the present invention may be brought into contact with an object as it is, and the disinfecting composition of the present invention is dissolved in a suitable solvent. You may make it contact with a target object after making it liquid state. The object of the disinfecting composition of the present invention is not particularly limited as long as microorganisms such as bacteria and fungi can grow, and may be an article or a part of a human body. When the disinfecting composition of the present invention is used as a liquid and brought into contact with a contact lens, the contact lens can be disinfected without changing the shape of the contact lens and without causing damage to the eye tissue. Such a solvent for contact lenses containing the disinfecting composition of the present invention is one embodiment of the present invention.

The solvent for contact lenses of the present invention comprises a disinfecting composition containing an effective amount of an organic nitrogen-based disinfectant and a phosphorylated oligosaccharide compound as basic constituent elements, and further has a cleaning property against dirt such as lipid and protein adhering to the contact lens. In order to improve, it is preferable to include at least one surfactant selected from the group consisting of an anionic surfactant, a cationic surfactant, a nonionic surfactant and an amphoteric surfactant. . In the present invention, a nonionic surfactant is preferably used in consideration of the influence on the optical characteristics such as deformation of the contact lens at the time of 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. And polyoxyethylene hydrogenated castor oil. Among these, a poly (oxyethylene) -poly (oxypropylene) block copolymer is preferable.

The compounding amount (concentration) of the surfactant is not particularly limited as long as it is a concentration that is usually used as a solvent for contact lenses. For example, it is 0.01 to 5.0 W / V%, and 0.05 to 1.0 W. / V% is preferable.

The pH of the contact lens solvent of the present invention is, for example, in the range of 6.4 to 8.4, preferably in the range of 6.9 to 7.9 in consideration of irritation to the eye and the stability of the contact lens material. It is set by adding a buffering agent or the like.

The buffering agent is not particularly limited as long as it is a buffering and water-soluble substance usually used in a solvent for contact lenses. For example, phosphate buffering agent, boric acid buffering agent, citrate buffering agent, trishydroxyaminomethane buffering Agents and the like. In the present invention, a borate buffer is preferred in view of the effect of inhibiting the growth of microorganisms.

The blending amount (concentration) of the buffering agent is not particularly limited. However, if the amount is too small, the desired buffering effect cannot be obtained. If the amount is too large, eye irritation or precipitation at low temperatures is a concern. It is 01-5.0 W / V%, Preferably it is 0.05-2.0 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 and the like. Various additives such as enzyme agents can be added.

Specifically, ethylenediaminetetraacetic acid, ethylenediaminetetraacetic acid / disodium, ethylenediaminetetraacetic acid / trisodium, citric acid, etc. as chelating agents; glycerin, propylene glycol, sorbitol, mannitol, etc. as tonicity agents; thickeners Examples thereof include polyvinyl alcohol and hydroxypropylmethylcellulose, but each drug is not limited to these.

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 phosphorylated oligosaccharide compound to purified water simultaneously or before and after each. Other components can also be added at the same time or before or after them.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples.

According to the formulation shown in Table 1, the liquid compositions of Examples 1 to 6 and Comparative Examples 1 to 3 of the present invention were prepared. That is, each compounding component was weighed into 100 mL of purified water so as to have a concentration (W / V%) described in Table 1, and sufficiently stirred at room temperature so that each component became uniform. The obtained uniform solution was sterilized by filtration with cellulose acetate having a pore size of 0.2 μm to prepare each liquid composition. About the prepared liquid composition of Examples 1-6 and Comparative Examples 1-3, according to the method shown below, disinfection effect, safety | security, and shape stability were evaluated. The results are shown in Table 2.

[1. Disinfection effect]
As test strains, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, and three types of fungus (Serratia marcescens ATCC 13880) and Candida albicans 31 were used.

For both bacteria and fungi, Dulbecco's phosphate buffer was added to the mycelia cultured on a slant medium of an agar medium at 35 ° C. for 18 hours, and the liquid recovered after suspension was used as the mycelia. Furthermore, the bacterial stock solution was diluted with Dulbecco's phosphate buffer to prepare a concentration of 10 ⁷ to 10 ⁸ cfu / mL, which was used as a bacterial test solution. The agar medium used is a soy bean casein agar medium for bacteria and a glucose peptone agar medium for fungi.

A sample obtained by inoculating 10 mL of the liquid composition with 0.1 mL of the fungus test solution was allowed to stand in a 25 ° C. incubator for a predetermined disinfection time (4 hours). After standing, 1 mL of the sample was added (diluted 10-fold) to 9 mL of an inert agent-containing medium (Neutralizing Broth), and further a 10-fold dilution series was continuously prepared in Dulbecco's phosphate buffer to obtain a test solution. 1 mL of the test solution at 3 concentration points at an appropriate dilution rate 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 bacterial test solution, was prepared by continuously preparing a 10-fold dilution series with Dulbecco's phosphate buffer and operating in the same manner as described above. 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 bacterial test solution, the amount of decrease in the viable count was determined as the logarithmic difference after the disinfection time in each sample by the following formula:
Decrease in viable count = initial count-viable count in the sample

In accordance with the primary standard of the ISO stand-alone test, the determination was that the amount of decrease in the number of viable bacteria during the 4-hour disinfection time was 3.0 or more for bacteria and 1.0 or more for fungi. Moreover, when comparing the disinfection ability between the 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. The results are shown in Table 2.

[2. safety]
Chinese hamster lung-derived cells V79 cells pre-cultured in a CO ₂ incubator at 37 ° C. were treated with trypsin and then suspended in fetal calf serum-containing Eagle's minimum essential medium. After dispensing each medium prepared so that the sample (liquid composition) concentration is 20%, 10%, 5%, and 2.5% in the well of the culture plate, the cell suspension is performed so that the number of cells becomes 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. Here, it was judged that there was safety when the relative colony formation rate was approximately 80% or more. The safety of each sample was evaluated by comparing the relative colony formation rate at the same concentration. The results are shown in Table 2.

[3. Stability]
As a test lens, seed 2weakFine UV and seed 2weakPure (both manufactured by Seed) were used. After taking out the contact lens from the blister package and removing the moisture on the surface, the contact lens was immersed in the liquid compositions of Examples 1 to 6 and Comparative Examples 1 to 3 dispensed in the lens case at room temperature for 4 hours and static. I put it.

Thereafter, in each liquid composition, the diameter of the contact lens was measured using a measurement microscope.
Judgment of stability for contact lens materials was made according to the contact lens approval standard, and when the amount of change in diameter before and after immersion in the liquid composition was within ± 0.2 mm with respect to the numerical value displayed on the product, it was judged as acceptable. . The results are shown in Table 2.

Phosphorylated oligosaccharide calcium: POs-Ca (Glyco Nutrition Foods)
Phosphorylated oligosaccharide sodium: POs-Na (Glyco Nutrition Foods)
Phosphorylated oligosaccharide magnesium: POs-Mg (Glyco Nutrition Foods)
Phosphorylated oligosaccharide potassium: POs-K (manufactured by Glico Nutrition Foods)

As described above, according to the present invention, a disinfecting composition and a contact lens solvent having a high disinfecting effect and high safety can be obtained.

Claims (4)

An antiseptic composition comprising an effective amount of an organic nitrogen-based disinfectant and a phosphorylated oligosaccharide compound, and used in a region other than the oral region ,
The phosphorylated oligosaccharide compound is phosphorylated oligosaccharide calcium, phosphorylated oligosaccharide sodium, phosphorylated oligosaccharide magnesium or phosphorylated oligosaccharide potassium;
The concentration of the organic nitrogen-based disinfectant is 0.0001 to 1.0 W / V%, and the concentration of the phosphorylated oligosaccharide compound is 0.0001 to 1.0 W / V%.
The disinfecting composition (excluding cosmetics) . The disinfecting composition according to claim 1, wherein the organic nitrogen disinfectant is a biguanide disinfectant or a quaternary ammonium disinfectant. The disinfecting composition according to claim 1, wherein the organic nitrogen-based disinfectant is polyhexamethylene biguanide, benzalkonium chloride or benzethonium chloride. The solvent for contact lenses containing the disinfecting composition of any one of Claims 1-3 .