JP2022055190A - Composition containing benzalkonium chloride - Google Patents

Abstract

To provide a composition containing benzalkonium chloride.SOLUTION: The inventive compositions contain benzalkonium chloride and paraben with a pH of 5.1 or more. Alternatively, the inventive compositions contain benzalkonium chloride, paraben, and a pH modifier.SELECTED DRAWING: None

Description

The present invention relates to a composition containing benzalkonium chloride and the like.

Benzalkonium chloride is a component used as a disinfectant (component for disinfection) and the like.
For example, Patent Document 1 describes that benzalkonium chloride or the like can be used as a disinfectant constituting the disinfectant in a wet wiper in which a fiber sheet is impregnated with a disinfectant.

Japanese Unexamined Patent Publication No. 2019-97756 (Claims, etc.)

An object of the present invention is to provide a novel composition or the like containing benzalkonium chloride.

Benzalkonium chloride (benzalkonium chloride) is used as a disinfectant or the like as described above.

Under these circumstances, the present inventor has created a composition capable of efficiently exhibiting bactericidal (antibacterial) performance by using benzalkonium chloride under specific conditions (in the coexistence of parabens, preferably further at a specific pH). I found that it could be obtained.

On the other hand, paraben is a component used as a preservative or the like, but according to the study of the present inventor, decomposition may proceed over time in the composition, and such decomposition may occur in other ways. It has been found that it can be more likely to progress in the presence of components (eg, pH regulators).

Under these circumstances, the present inventor has combined paraben with benzalkonium chloride (particularly in the presence of other components such as a pH preparation) to stabilize the paraben (storage stability, stability over time). It was also found that the sex or decomposition stability) can be improved or improved.

That is, the present invention relates to the following inventions and the like.
[1]
A composition containing benzalkonium chloride and paraben and having a pH of 5.1 or higher.
[2]
A composition containing benzalkonium chloride, parabens, and a pH regulator.
[3]
The composition according to [1] or [2], wherein the ratio of benzalkonium chloride is 0.01 to 10 w / v%.
[4]
The composition according to any one of [1] to [3], wherein the paraben comprises at least one selected from methylparaben and ethylparaben.
[5]
The composition according to any one of [1] to [4], wherein the paraben contains methylparaben and ethylparaben.
[6]
The composition according to any one of [1] to [5], wherein the proportion of paraben is 1% by mass or less.
[7]
The composition according to any one of [1] to [6], which comprises 0.05 parts by mass or more of paraben with respect to 1 part by mass of benzalkonium chloride.
[8]
The composition according to any one of [1] to [7], which contains a pH adjuster exhibiting basicity.
[9]
The composition according to any one of [1] to [8], which contains water and substantially no ethanol (alcohol).
[10]
The composition according to any one of [1] to [9], which has a pH of 5.3 or higher.
[11]
The composition according to any one of [1] to [10], which has a pH of 5.5 to 7.
[12]
The composition according to any one of [1] to [11], which has a pH of 6 to 6.5.
[13]
The composition according to any one of [1] to [12], which is for disinfection (disinfectant).
[14]
The composition according to any one of [1] to [13], which is for skin disinfection (disinfectant).
[15]
A method of blending paraben with a composition containing benzalkonium chloride to improve the bactericidal activity of the composition.
[16]
A method of blending benzalkonium chloride with a composition containing paraben to improve the stability of paraben in the composition.
[17]
The method according to [15] or [16], wherein the pH of the composition is 5.1 or higher.
[18]
The method according to any one of [15] to [17], wherein the composition contains a pH adjuster.

According to the present invention, it is possible to provide a novel composition or the like containing benzalkonium chloride.

In one aspect of such a composition, the bactericidal performance can be efficiently exhibited by using benzalkonium chloride under specific conditions. In particular, according to such a composition, bactericidal activity can be exhibited even if it is water-based (aqueous composition) or ethanol-free. And, in such a composition, the bactericidal power can be maintained or maintained for a long period of time.

Also, in one aspect of the composition, the stability of parabens can be improved or improved. According to such compositions, the stability of parabens (even if they are water-based (aqueous composition) or ethanol-free [and even if they contain other components (eg, pH regulators)] Stability over time, decomposition stability) can be improved or improved. Therefore, according to such a composition, the function of parabens (for example, antiseptic performance) can be maintained or maintained.

Furthermore, in one aspect of the composition, both bactericidal function and paraben stability (and thus paraben function over a long period of time) can be compatible. Such compatibility can be achieved even if it is water-based (aqueous composition) or ethanol-free [furthermore, even if it contains other components (for example, a pH adjuster)].

As described above, the composition of the present invention is highly useful and can be used for various purposes.
In particular, as described above, since it can exhibit bactericidal performance even if it is ethanol (alcohol) -free, it is a composition for skin disinfection (for hand disinfection) that can be used even for subjects with alcohol hypersensitivity. Can be used as.

[Composition]
The composition (formulation) of the present invention contains at least benzalkonium chloride and paraben.

(Benzalkonium chloride)
Examples of benzalkonium chloride (benzalkonium chloride) include the components described in the 17th revised Japanese Pharmacopoeia Pharmaceuticals Article "Benzalkonium Chloride".
Specifically, benzalkonium chloride may be a compound represented by the formula [C ₆ H ₅ CH ₂ N (CH ₃ ) ₂ R] Cl.
In this formula, R is an aliphatic hydrocarbon group (alkyl group). A typical R includes an alkyl group having 8 to 18 carbon atoms (C ₈ H ₁₇ to C ₁₈ H ₃₇ ). R may include (consiste of) primarily C ₁₂ H ₂₅ and C ₁₄ H ₂₉ .
In the composition, the ratio of benzalkonium chloride depends on the use, purpose of use (for example, disinfection purpose, purpose of stabilizing paraben, etc.) or mode of use (when diluting, etc.) of the composition, but is, for example, 0. It may be 001 w / v% or more, preferably 0.005 w / v% or more, more preferably 0.01 w / v% or more, and the like.

The upper limit of the ratio of benzalkonium chloride is not particularly limited, but may be, for example, 10 w / v% or less, preferably 2 w / v% or less, more preferably 0.2 w / v% or less.

Typically, the proportion of benzalkonium chloride is, for example, 0.001 to 10 w / v%, preferably 0.005 to 2 w / v%, and more preferably 0.01 to 0.2 w / v%. There may be.

The ratio of benzalkonium chloride may be selected in a suitable range depending on whether it is the product concentration or the concentration used, and the efficacy / effect.
Suitable concentrations for each indication (purpose of use) are illustrated below.

Disinfection of fingers and skin: 0.05-0.1w / v%
Disinfection of the skin at the surgical site: 0.1-0.2w / v%
Disinfection of the mucous membrane of the surgical site and the wound site of the skin / mucous membrane: 0.01-0.025w / v%
Disinfection of infected skin surface: 0.01w / v%
Disinfection of medical equipment: 0.1w / v%
Disinfection of operating rooms, hospital rooms, furniture, instruments, articles, etc .: 0.05-0.2w / v%
Vaginal lavage: 0.02-0.05w / v%
Cleaning and disinfection of the conjunctival sac: 0.01-0.05w / v%

(Paraben)
Examples of parabens include paraoxybenzoic acid alkyl esters [eg, methylparaben (methyl paraoxybenzoate), ethylparaben (ethyl paraoxybenzoate), propylparaben, isopropylparaben, butylparaben, isobutylparaben, etc.], benzylparaben and the like. Be done.

In addition, paraben may form a salt [for example, a metal salt such as methylparaben sodium (for example, an alkali metal salt such as sodium salt)] (or paraben may contain a salt).

Parabens may be used alone or in combination of two or more.

Of these, paraoxybenzoic acid alkyl esters are preferable, and in particular, parabens may contain at least methylparaben and / or ethylparaben, and may contain methylparaben and ethylparaben.
Methylparaben and ethylparaben (particularly methylparaben) are preferable from the viewpoint of function (antibacterial activity, etc.) and water solubility (and thus inhibition of precipitation in the composition), and are particularly functional (further improvement of function such as antibacterial activity by combined use) and water dissolution. From the viewpoint of sex balance and the like, it is preferable to combine methylparaben and ethylparaben.
By using such a paraben, it is possible to efficiently exert its function (antibacterial activity, etc.) without using (or suppressing its use) a component (dissolution aid) for promoting dissolution (suppressing precipitation). ..
When a large amount of such a solubilizing agent is used, another problem (deterioration of usability, increased skin irritation, etc.) due to the solubilizing agent may occur, and as a result, the balance adjustment of the entire formulation becomes complicated. Although the hurdles for formulation may be high, such a problem can be prevented by appropriately selecting parabens.

When the paraben contains methylparaben and / or ethylparaben, the ratio of methylparaben and / or ethylparaben to the total paraben is, for example, 30% by mass or more, preferably 50% by mass or more, and more preferably 70% by mass or more (for example). , 80% by mass or more), 90% by mass or more, or 100% by mass (substantially parabens are methylparaben and / or ethylparaben only).

When the paraben contains methylparaben and ethylparaben, the ratio thereof is not particularly limited, but for example, 0.01 to 100 parts by mass, preferably 0.05 to 20 parts by mass of ethylparaben with respect to 1 part by mass of methylparaben. More preferably, it may be 0.1 to 10 parts by mass.

In the composition, the ratio of paraben depends on the use of the composition, the purpose of use (for example, antiseptic purpose, improvement of bactericidal performance, etc.) or the mode of use (when diluting, etc.), but is, for example, 1 w / v% or less. It may be preferably 0.5 w / v% or less, more preferably 0.25 w / v% or less, and the like.

In one aspect of the composition of the present invention, since paraben can be stabilized, the function of paraben can be efficiently exhibited even in a relatively small proportion (usage amount).

The lower limit of the ratio of paraben is not particularly limited, but may be, for example, 0.005 w / v% or more, preferably 0.01 w / v% or more, and more preferably 0.02 w / v% or more.

Typically, the proportion of parabens is, for example, 0.005 to 1 w / v%, preferably 0.01 to 0.5 w / v%, more preferably 0.02 to 0.25 w / v%, and the like. You may.

The ratio of benzalkonium chloride to paraben is, for example, 0.01 part by mass or more (for example, 0.05 part by mass or more), preferably 0.1 part by mass or more, with respect to 1 part by mass of benzalkonium chloride. It may be more preferably 0.2 parts by mass or more, 20 parts by mass or less, preferably 10 parts by mass or less, and further preferably 5 parts by mass or less.

(PH regulator)
The composition may include a pH regulator. The pH adjuster is not particularly limited as long as it is a component that can adjust (variate) the pH, and can be appropriately selected according to a desired pH, and may be a basic (basic component) or an acidic (acidic component,). It may be an acid component).

Further, the pH adjusting agent may have a buffering action alone or by a combination of two or more kinds of components (pH adjusting agents). When two or more components are combined, the combination (whole pH adjuster) may be basic or acidic (may be basic or acidic).

Examples of the pH adjuster include inorganic acids [eg, phosphoric acid, pyrophosphate, metaphosphate, polyphosphoric acid, sulfuric acid, nitrate, hydrochloric acid (hydrogen chloride), etc.] and salts of inorganic acids (eg, weak acids) [eg, phosphorus]. Acid hydrogen salt (eg, sodium hydrogen phosphate), dihydrogen phosphate (eg, sodium dihydrogen phosphate)], organic acid {eg, monocarboxylic acid (eg, acetic acid, sorbic acid), polycarboxylic acid (eg, eg acetic acid, sorbic acid). , Shuic acid, succinic acid, maleic acid, fumaric acid), oxycarboxylic acid [eg, hydroxymonocarboxylic acid (eg, glycolic acid, lactic acid, gluconic acid), hydroxypolycarboxylic acid (eg, tartrate acid, malic acid, citric acid) Etc.], etc.}, salts of organic acids (eg, weak acids) [eg, sodium acetate, sodium tartrate, sodium succinate, sodium citrate (trisodium citrate, etc.) (Salts of carboxylic acids)], inorganic bases [eg, metal hydroxides (eg, sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), etc.], organic bases {eg, amines [eg, alkanolamines (eg, alkanolamines). Monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, N-methylethanolamine, N-aminoethylethanolamine, N-methyldiethanolamine, etc.)], etc.}, amino acids (eg, glycine, etc.), etc. Can be mentioned.

The pH regulator may be used alone or in combination of two or more.

In particular, as the pH adjuster, at least a pH adjuster exhibiting basicity may be used.

When the composition contains a pH adjuster, the proportion of the pH adjuster in the composition can be selected according to the type, desired pH and the like. For example, in the case of anhydrous sodium monohydrogen phosphate and anhydrous sodium dihydrogen phosphate, it is 0.01 to 1 w / v%, preferably 0.05 to 0.5 w / v%, and more preferably 0.1 to 0.3 w /. It may be v% or the like.

In the composition of one aspect of the present invention, the stability of paraben can be efficiently realized even if other components such as a pH adjuster coexist, so that the pH can be adjusted to a desired level while ensuring the stability of paraben. It's easy to do.

(Other ingredients)
The composition may contain other components. In addition, other components showing basicity or acidity may function as a pH adjuster.

Other components can be selected according to the purpose and mode of use of the composition, for example, a wetting agent (moisturizing agent), a thickening agent (viscosity adjusting agent, thickening agent), a defoaming agent, and a bactericidal (antibacterial) agent. , Preservatives, surfactants (cationic surfactants, anionic surfactants, nonionic surfactants, amphoteric surfactants), deodorants, fragrances, medicinal ingredients (physiologically active ingredients, active ingredients), Stabilizers, improvers, plasticizers, solubilizers, reducing agents, buffers, bases, volatile aids, flavoring agents, surfactants, suspending agents, antioxidants, Efficacy enhancer, sustainer, wetting adjuster, filler, defoamer, refreshing agent, enhancer, flavoring agent, colorant, tonicity agent, softening agent, emulsifier, thickening agent, foaming agent , Skin protectants, buoyants, dispersants, propellants, fragrances, rust preventives, preservatives, solubilizers, solubilizers and the like.

In addition, other components may have a plurality of functions. For example, depending on the type, the surfactant may function as a bactericidal (disinfectant) agent, a foaming agent (foaming agent), or the like, and the wetting agent may function as a viscous agent or the like.

Examples of such other components include polyhydric alcohols {eg, alcan diols (eg, ethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butanediol, 3-methyl-1). , 3-Butanediol, Pentandiol), multimers of alcohol (eg, diethylene glycol, triethylene glycol, dipropylene glycol), polyethylene glycol (macrogol), polyoxyethylene polyoxypropylene glycol (poroxamer), 3 or more Polyhydric alcohols with hydroxy groups [eg, glycerin, diglycerin, sugars or sugar alcohols (eg, trehalose, etc.)], etc.}, polysaccharides or derivatives thereof (eg, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydrophobic). Hydroxypropylmethylcellulose, carboxymethylcellulose (sodium carboxymethylcellulose), hyaluronic acid (sodium hyaluronate), guar gum, carrageenan, locust bean gum, xanthan gum, etc.), cationic surfactants (eg, cetylpyridinium chloride, benzethonium chloride chloride) , Decalinium chloride, didecyldimethylammonium chloride, N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate, etc.), amphoteric surfactants (eg, lauryldimethylamine oxide, alkyldiaminoethylglycine hydrochloride) Salts, etc.), nonionic surfactants [eg, polyoxyethylene hydrogenated castor oil, alkyl glucosides (eg, decyl glucoside, caprylyl / capryl glucoside, etc.), etc.], antibacterial agents or preservatives [eg, phenoxyethanol, chlorhexidine gluconate, etc.] , Dehydroacetic acid or a salt thereof (sodium benzoate, etc.), Dehydroacetic acid or a salt thereof (sodium dehydroacetate, etc.), Glycyrrhizinic acid or a salt thereof (dipotassium glycyrrhizinate, etc.), etc.], Dissolution aid (eg, isopropyl myristate, etc.) , Solubilizing agents (eg, glycerin fatty acid esters, etc.), Stabilizing agents (eg, tocopherol acetate, etc.), Wetting or softening agents (eg, allantin, urea, 2-methacryloyloxyethyl phosphorylcholine methacryl) Examples thereof include butyl acid acid copolymer liquid (lipidure (registered trademark)) and the like.

Other ingredients may be used alone or in combination of two or more.

In the composition of one aspect of the present invention, the stability of paraben is efficiently maintained even in the presence of other components as described above (for example, polyhydric alcohol, polysaccharide or derivative thereof, allantin, surfactant, etc.). Since it can be realized, it is possible to efficiently impart functions according to the types of other components to the composition while ensuring the stability of the paraben.

On the other hand, the composition of the present invention does not have to contain other components as described above. For example, in the present invention, the composition may contain an antibacterial agent or an antiseptic (for example, phenoxyethanol) because the functions of benzalkonium chloride and / or paraben can be efficiently exerted (expressed). You don't have to.

When the composition contains other components, the ratio of the other components in the composition can be appropriately selected according to the type, purpose of use and the like.

The other components (total amount) in the composition are, for example, 60 w / v% or less, preferably 50 w / v% or less, more preferably 30 w / v% or less (for example, 20 w / v% or less, 15 w / v% or less). (10 w / v% or less, etc.), etc., 0.001 w / v% or more, preferably 0.01 w / v% or more, still more preferably 0.1 w / v% or more (for example, 0.15 w / v). It may be v% or more, 0.2 w / v% or more, etc.).

When the composition contains a polyhydric alcohol, the proportion of the polyhydric alcohol in the composition is 50 w / v% or less (eg, 45 w / v% or less), preferably 30 w / v% or less (eg, 20 w / v%). Below), more preferably 10 w / v% or less (for example, 5 w / v% or less, 3 w / v% or less, 1 w / v% or less), and more, 0.001 w / v% or more, preferably 0. It may be 0.01 w / v% or more, more preferably 0.05 w / v% or more (for example, 0.1 w / v% or more).

When the composition contains a polysaccharide or a derivative thereof, the ratio of the polysaccharide or its derivative in the composition is 5 w / v% or less, preferably 3 w / v% or less, more preferably 1.5 w / v% or less, and the like. It may be 0.001 w / v% or more, preferably 0.005 w / v% or more, more preferably 0.01 w / v% or more, and the like.

When the composition contains allantoin, the proportion of allantoin in the composition is 3 w / v% or less, preferably 1 w / v% or less, more preferably 0.1 w / v% or less (eg, 0.05 w / v%). The following) may be used, and may be 0.001 w / v% or more, preferably 0.005 w / v% or more, and more preferably 0.01 w / v% or more.

The ratio of the other component to the paraben may be, for example, 0.1 part by mass or more, preferably 0.5 part by mass or more, and more preferably 1 part by mass or more of the other component with respect to 1 part by mass of the paraben. , 50 parts by mass or less, preferably 30 parts by mass or less (for example, 20 parts by mass or less), and more preferably 10 parts by mass or less.

(solvent)
The composition may contain a solvent (carrier, solvent component).

Examples of the solvent include water, non-aqueous solvents [for example, alcohols (or monools, for example, lower alcohols such as ethanol and isopropanol)] and the like.

In addition, the above-mentioned pH adjuster (for example, alkanolamine etc.) and other components (for example, polyhydric alcohol etc.) can also be used as a non-aqueous solvent.

The non-aqueous solvent may be typically a water-soluble solvent (or a solvent miscible with water).

The solvent is usually preferably composed of at least water. That is, the composition of the present invention may usually contain at least water, or may contain water and a non-aqueous solvent.

When water and a non-aqueous solvent are used in combination, the ratio of water is 50% by mass or more, preferably 70% by mass or more, and more preferably 90% by mass or more with respect to the total amount of water and the non-aqueous solvent. You may.

In particular, the composition of the present invention may contain, in small amounts, or substantially no lower alcohol (particularly ethanol). In the composition of the present invention, benzalkonium chloride can efficiently exhibit antibacterial performance even if it does not contain a solvent such as ethanol that can exhibit antibacterial performance. Therefore, the present invention can also provide such [or alcohol (particularly, ethanol) -free] compositions with low or substantially no alcohol (particularly ethanol) content.

In such a composition, the proportion of ethanol (lower alcohol) may be, for example, 5% by mass or less, preferably 3% by mass or less, more preferably 1% by mass or less, and particularly 0% by mass. It may (ie, the composition may not contain ethanol).

(PH)
The pH of the composition of the present invention can be selected from a range of, for example, about 3 or more (for example, 4 or more), 4.2 or more (for example, 4.5 or more, 4.8 or more), and preferably 5 or more (for example, 4 or more). 5.2 or more, 5.5 or more, 5.8 or more, 5.9 or more), more preferably 6 or more.

The upper limit of the pH of the composition can be selected from a range of, for example, about 10 or less, and may be 9 or less, 8.5 or less, 8 or less, 7.5 or less, 7 or less, 6.5 or less, and the like.

In particular, the pH of the composition is 5.1 or higher (for example, 5.2 or higher, 5.3 or higher, 5.4 or higher, 5.5 or higher, 5.6 or higher, 5.7 or higher) from the viewpoint of bactericidal performance or the like. It is preferably about 5.8 or more, 5.9 or more, 6 or more).

On the other hand, the pH of the composition may be about 7.4 or less (for example, 7.3 or less, 7.2 or less, 7.1 or less) from the viewpoint of paraben stability and the like, and is preferably 7 or less. (For example, 6.9 or less, 6.8 or less, 6.7 or less, 6.6 or less), more preferably 6.5 or less.

Therefore, the pH of the composition is in a range (for example, 5.5 to 7, 6 to 6.5, etc.) that combines (overlaps) these ranges from the viewpoint of achieving both bactericidal performance and the stability of parabens. ) May be.

The pH may be measured, for example, in accordance with the 17th revised Japanese Pharmacopoeia General Test Method 2.54 “pH Measurement Method”. The pH may be, for example, a value at a growing temperature (for example, 20 to 25 ° C.).

(Form / Manufacturing method)
The form (property) of the composition is usually liquid. The liquid composition may be a solution, a suspension, an emulsion, or the like, or may be a cream (cream), depending on the components of the composition and the like. Further, the composition (composition at the time of use) may be in the form of a gel (gel), foam (foam) or the like.

The viscosity of the liquid composition may be, for example, 30,000 mPa · s or less, preferably 10,000 mPa · s or less, more preferably 5000 mPa · s or less, and 1 mPa · s or more (for example, 2 mPa · s or more, 3 mPa · s). 5 mPa · s or more, 10 mPa · s or more, etc.).
The viscosity can be measured with a Uberode type viscometer (temperature 20 ° C.) according to, for example, the 17th revised Japanese Pharmacopoeia general test method 2.53 “viscosity measurement method” 1st method capillary viscometer method.

The composition can be obtained by mixing each component. The mixing method (manufacturing method) is not particularly limited, and a conventional method can be used.

(Use)
The use of the composition is not particularly limited, and it can be used for various uses. For example, the composition can be applied to applications that take advantage of the disinfection (sterilization) performance of benzalkonium chloride.

On the other hand, since the composition contains paraben, it can be applied to applications that make the best use of the function of paraben (antiseptic performance, etc.).

The composition of the present invention is typically suitably used for disinfection (disinfectant), and in particular, for external disinfection (external disinfectant). Examples of external use (disinfectant) include skin (disinfectant) [for example, fingers (disinfectant)]. The composition of the present invention can be composed of safe ingredients and is also suitable for external use (skin).

In particular, in the present invention, it is possible to obtain a composition that does not substantially contain ethanol (alcohol), so that such a composition can be applied to a subject (user) who is sensitive to ethanol (alcohol).

(Usage pattern)
The form of use (application method) of the composition can be appropriately selected depending on the purpose of use, form (property), etc. of the composition, and can be used, for example, by applying it to a target (application) site.

Specific application methods include application (adhesion) to the target site. Specific application methods include, for example, dropping from a container or spraying with a pump in the case of a liquid composition, dropping from a container or discharging from a pump in the case of a gel-like composition, and foam. Examples of the composition include discharge by a pump or spraying with gas (compressed gas).
Further, the composition (chemical solution) may be taken on gauze, a towel, a mop, a wipe or the like and applied or wiped on an article or an environmental surface. Further, a method of immersing the object in the composition (chemical solution) may be used.

The composition may be contained in a suitable container. The container may be selected according to the application method.

For example, the composition may be sprayed (sprayed) by accommodating it in a spray container (spray bottle), or by accommodating it in a container capable of forming bubbles (foam bottle, for example, a container with a mesh). It may be possible to apply (apply, spray) as a foam.

The applied amount (used amount) of the composition can be selected according to the purpose of use and the like. For example, in the case of hand disinfection, 0.1 to 6 mL, preferably 0.2 to 3 mL, and more preferably 0.4 is applied once. It may be ~ 1 mL or the like.

The application amount (usage amount) of the composition can be selected according to the purpose of use and the like. For example, in the case of hand disinfection, 0.05 to 12 mg, preferably 0.1 to 12 mg of benzalkonium chloride is used at one time. It may be 6 mg, more preferably 0.2 to 2 mg or the like.

[Various methods]
In the present invention, as described above, the bactericidal performance (bactericidal activity) of the composition can be improved (improved) and the stability of paraben can be improved (improved).
Therefore, the present invention also includes the following method.

(1) A method of blending (containing) paraben with a composition containing benzalkonium chloride to improve the bactericidal activity of the composition.

(2) A method of blending (containing) benzalkonium chloride with a composition containing paraben to improve the stability of paraben in the composition.

In these methods, the above-mentioned examples may be used except for the blending of benzalkonium chloride and paraben. For example, the blending amount (ratio) of benzalkonium chloride or paraben may be selected from the above range, and the presence or absence of blending of pH and other components (for example, a pH adjuster) and the percentage thereof are also exemplified above. It may be a thing.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto.

In the examples, various measurements and tests were performed as follows.

pH measurement The measurement was carried out at the Nariyuki temperature (20 to 25 ° C) according to the 17th revised Japanese Pharmacopoeia General Test Method 2.54 “pH Measurement Method”.

Measurement of the content of each component The measurement was performed according to the 17th revised Japanese Pharmacopoeia General Test Method 2.01 "Liquid Chromatography (Internal Standard Method)".

Time Kill Test (ASTM E2315-16) 1
A Time-kill test (ASTM E2315-16) was performed on each composition to determine the time to reach a logarithmic reduction value of 5.0 (sterilization rate 99.999%). The following two species were used as the fungus.
Burkholderia Sepasia NBRC 15124 strain Candida albicans NBRC 1594 strain

Time Kill Test (ASTM E2315-16) 2
A Time-kill test (ASTM E2315-16) was performed on each composition, and the logarithmic reduction values at 30 seconds and 60 seconds were determined. The following was used as the fungus.
Burkholderia Sepasia NBRC 15124 strain

Stability test 60 mL of each composition was filled in a polyethylene container, and the test sample capped with a polypropylene cap was stored at 50 ° C. at time points [at the start of the test, 10 days, 20 days, 40 days (Test Example B). Only)], the content of each component (4-hydroxybenzoic acid, paraben) was measured. In addition, the pH was measured every 10 days, 20 days, and 40 days (only in Test Example B).

The pH was measured by the above method, and the content of each component was measured by the above method. For parabens (methylparaben, ethylparaben), the content at the start of the test was set to 100%, and 10 days and 20 days. The content (relative value (%)) after 40 days was calculated.

Test Example A
As shown in Table 1 below, each component was mixed in a predetermined amount ratio to obtain each composition (test preparation).

Then, Time Kill test 1 and stability test were performed on each of the obtained compositions. The results are summarized in Table 1 below.

In Table 1, "part" indicates a mass part, and "ND" indicates a detection limit (not detected) (the same applies hereinafter).

The results in the above table show that in the composition containing benzalkonium chloride, even if it is ethanol-free, specific conditions (conditions containing parabens, preferably further pH of about 5.5 or more, particularly 6 or more) are obtained. ), It was shown that the bactericidal performance can be efficiently exhibited (formulations A1 to A5, particularly formulations A1 to A4, etc.).

In particular, when considering the use for disinfecting the skin (hands and fingers, etc.), it is preferable that the use time (drying time) is short (for example, within 60 seconds), and such a short time (for example, due to bacteria). It is extremely useful to be able to sterilize within 15 seconds, 60 seconds, etc.).

On the other hand, from the results of the stability test, although the pH did not fluctuate over time, the amount of 4-hydroxybenzoic acid, which is considered to be caused by the decomposition (hydrolysis) of paraben, increased, and the residual amount of paraben increased. There was a tendency to decrease (increase the disappearance of parabens), but this tendency was that it contained benzalconium chloride and was generally pH 7 or less [especially 6.5 or less (5 to 6.5, 5.5 to 6.5). Etc.)] was found to be significantly suppressed (formulations A2 to A6, particularly formulations A3 to A6).

Therefore, from the viewpoint of achieving both bactericidal performance (maintenance) and paraben function (for example, antiseptic performance) at a high level, it contains benzalkonium chloride and paraben, and has a pH of 5.5 to 7 (particularly 6). It was also found that the compositions of ~ 6.5) (formulations A2 to A5, particularly formulations A3 to A4) are extremely suitable.

In addition, the results in the above table show that the stabilizing effect of ethylparaben is generally high among parabens, and that the stability of methylparaben is significantly improved under specific pH conditions (for example, 7 or less, particularly 6.5 or less). It shows what you can do.

Test Example B
As shown in Table 2 below, each component was mixed in a predetermined amount ratio to obtain each composition (test preparation).

Then, a stability test was conducted on each of the obtained compositions. The results are summarized in Table 2 below.

The results in the above table show that in a composition containing paraben (ethanol-free aqueous composition), the stability of paraben tends to decrease due to the coexistence of other components (pH adjuster, etc.), and benzalkonium chloride. It has been shown that luconium can improve or improve the stability of parabens.

Test Example C
As shown in Table 3 below, each component was mixed in a predetermined amount ratio to obtain each composition (test preparation).

Then, Time Kill test 2 was performed on each of the obtained compositions. The results are summarized in Table 3 below.

The results in the above table show that the bactericidal performance can be exhibited more efficiently by combining benzalkonium chloride and paraben (further, combining them in a predetermined pH range).

Test Example D
As shown in Table 4 below, each component was mixed in a predetermined amount ratio to obtain each composition.

Then, when the Time Kill test 1 and the stability test were performed on each of the obtained compositions, the same tendency as described above was shown.

According to the present invention, it is possible to provide a composition or the like that can be used for disinfection or the like.

Claims (18)

A composition containing benzalkonium chloride and paraben and having a pH of 5.1 or higher. A composition containing benzalkonium chloride, parabens, and a pH regulator. The composition according to claim 1 or 2, wherein the ratio of benzalkonium chloride is 0.01 to 10 w / v%. The composition according to any one of claims 1 to 3, wherein the paraben comprises at least one selected from methylparaben and ethylparaben. The composition according to any one of claims 1 to 4, wherein the paraben comprises methylparaben and ethylparaben. The composition according to any one of claims 1 to 5, wherein the proportion of paraben is 1% by mass or less. The composition according to any one of claims 1 to 6, which comprises 0.05 parts by mass or more of paraben with respect to 1 part by mass of benzalkonium chloride. The composition according to any one of claims 1 to 7, which contains a pH adjuster exhibiting basicity. The composition according to any one of claims 1 to 8, which contains water and substantially no ethanol. The composition according to any one of claims 1 to 9, wherein the pH is 5.3 or more. The composition according to any one of claims 1 to 10, wherein the pH is 5.5 to 7. The composition according to any one of claims 1 to 11, wherein the pH is 6 to 6.5. The composition according to any one of claims 1 to 12, which is for disinfection. The composition according to any one of claims 1 to 13, which is for skin disinfection. A method of blending paraben with a composition containing benzalkonium chloride to improve the bactericidal activity of the composition. A method of blending benzalkonium chloride with a composition containing paraben to improve the stability of paraben in the composition. 15. The method of claim 15 or 16, wherein the pH of the composition is 5.1 or higher. The method according to any one of claims 15 to 17, wherein the composition contains a pH adjuster.