KR101935904B1 - A preservative for skin external application, and a cosmetic composition and a pharmaceutical composition comprising the same - Google Patents

Abstract

The present invention relates to a preservative for skin external application, which has very excellent preservation ability and is very safe, and a cosmetic composition and pharmaceutical composition including the preservative. The preservative for skin external application of the present invention comprises a combination of tyrosol and chavicol, wherein the tyrosol and the chavicol are included at a weight ratio of 1 to 4.0:0.04 to 0.08.

Description

[0001] The present invention relates to a preservative for external preparation for skin, a cosmetic composition comprising the same, and a pharmaceutical composition comprising the same,

The present invention relates to a preservative for external preparations for skin, a cosmetic composition and a pharmaceutical composition containing the same, which can provide a synergistic antimicrobial activity by containing a combination of a natural product derived material and can provide toxicity, skin irritation, And a preservative for external preparation for skin which does not cause allergy, and a cosmetic composition and a pharmaceutical composition containing the preservative.

Since the cosmetic composition and the pharmaceutical composition for external application for skin are inevitably contaminated with microorganisms during the manufacturing process and use, a preservative is used for the purpose of improving the preservability of the product. Widely used as such preservatives are preservatives such as parabens (sodium paraoxybenzoate), imidazolidinyl urea, phenoxyethanol and the like. These preservatives are highly preservative because of their high antibacterial activity, but they are often known to cause toxicity, skin irritation, and allergies. Therefore, a preservative for external preparation for skin having high preservability without inducing skin irritation has been developed, and there is a need to develop a preservative for external skin preparations which has better preservation ability and is safe.

Tyrosol having a structure represented by the following formula (1) can be obtained from wine, olive oil, argan oil, Ligustrum lucidum , Olea europaea , and Plantago major, among others. Tyrosol is also known to have an antibacterial effect (Non-Patent Document 1)

[Chemical Formula 1]

Fare to the call having the structure of Formula 2 (Chavicol) is Agastache rugosa , Alpinia galanga , Pineapple comosus , Cinnamomum aromaticum , Melia azedarach , Ocimum basilicum , Origanum majorana , Pimenta dioica , Pimenta racemosa , Pimenta dioica , Piper betel, Syzygium aromaticum , Tagetes lucida , Zingiber officinale , and many other articles related to antioxidative and antibacterial effects have been reported.

(2)

Alem MA, Oteef MD, Flowers TH, Douglas LJ (2006). Production of tyrosol by Candida albicans biofilms and its role in quorum sensing and biofilm development. Eukaryot. Cell 5 (10): 1770-1779

An aspect of the present invention is to provide a preservative for external preparation for skin which is excellent in preservation power and does not cause skin irritation and is safe.

Another aspect of the present invention is to provide a cosmetic composition comprising the preservative for external preparation for skin.

Another aspect of the present invention is to provide a pharmaceutical composition comprising the preservative for external preparation for skin.

Another aspect of the present invention is to provide a method for producing an external preparation for skin, which comprises using the preservative for external preparation for skin as a preservative.

One aspect of the present invention provides a preservative for external preparation for skin comprising a combination of tyrosol and chibicol.

Another aspect of the present invention provides a cosmetic composition comprising the preservative for external preparation for skin.

Another aspect of the present invention provides a pharmaceutical composition comprising the preservative for external preparation for skin.

Another aspect of the present invention provides a method for producing an external preparation for skin comprising using the preservative for external preparation for skin as a preservative.

According to one embodiment of the present invention, it is possible to provide a preservative for external preparation for skin, which has excellent preservation power and is significantly less irritating to the skin than conventionally used chemical preservatives. Therefore, according to one embodiment of the present invention, a cosmetic composition and a pharmaceutical composition having high preservability and safety can be produced by using the preservative for external preparation for skin.

Hereinafter, the present invention will be described in more detail.

All technical terms used in the present invention are used in the sense that they are generally understood by those of ordinary skill in the relevant field of the present invention unless otherwise defined. In addition, preferred methods or samples are described in this specification, but similar or equivalent ones are also included in the scope of the present invention. Also, the numerical values set forth herein are considered to include the meaning of " about " unless explicitly stated. The contents of all publications referred to in this specification are incorporated herein by reference in their entirety.

Herein, the term " external preparation for skin " is a concept covering the entire composition applied to the skin, and includes various cosmetic materials such as basic cosmetics, makeup cosmetics, and hair cosmetics; A pharmaceutical composition such as an ointment preparation, a cream preparation, a rosophage and the like, and a pharmaceutical composition applied to the external skin including quasi-drugs.

"Antibacterial" means resistance to the overall contaminated microorganisms such as bacteria, fungi and yeast. "Antimicrobial activity" means a defense against these contaminating microorganisms. Bacterial activity, antifungal activity against fungi and / or yeast.

&Quot; Buoyancy force " means a defense against decay by microbial contamination, including the concept of antibacterial activity.

"Preservative" refers to a substance that has buoyant or antioxidant capacity to prevent deterioration of the product for a long time and maintain its original condition. "Preservative" refers to a substance that protects against deterioration of the product over time and maintains its original state. it means.

The present inventors have found that a preservative for external preparation for skin can be obtained even when a conventional chemical preservative such as paraben or phenoxyethanol is not added to a user having an extremely sensitive skin and can maintain a retention equal to or greater than that of a conventional chemical preservative .

As a result, it has been found that the combination of tyrosol and chibicol, which are present in natural substances and known to have antioxidative effects, has a synergistic antifungal effect and antibacterial activity (Test Example 2), and skin irritation was remarkably low (Test Examples 3 and 4). The results are shown in Table 1.

Accordingly, in one aspect, the present invention provides a preservative for external preparation for skin comprising a combination of tyrosol and chibicol.

The thyrosol may be chemically synthesized, and Ligustrum lucidum , Olea europaea, Plantago major, and any combination thereof.

The fare call may be a chemically synthesized, Agastache rugosa , Alpinia galanga , Pineapple comosus , Cinnamomum aromaticum , Melia azedarach , Ocimum basilicum , Origanum majorana , Pimenta dioica , Pimenta racemosa , Pimenta dioica , Piper betel, Syzygium aromaticum , Tagetes lucida , Zingiber officinale, and any combination thereof.

The ratio of the combination of the two components contained in the preservative for external preparation for skin includes any proportion showing effective antibacterial activity. In one embodiment, the tyrosol and chibicol can be included in a weight ratio of about 0.5 to 6.0: 0.02 to 0.10, more specifically about 1 to 4.0: 0.04 to 0.08, and more specifically 1 to 3.5: 0.06 0.08 < / RTI > by weight. In one embodiment, the preservative for topical application to the skin may comprise tyrosol and chbarcall at a weight ratio of about 1: 0.08.

As a result of the test, the antibacterial activity against bacterium and fungus was increased synergistically compared to the case where each of the preservatives for external preparations for skin including Chibikol and Thyrosol according to one embodiment of the present invention was used singly, The antifungal activity of tyrosol alone was very weak, and the combination of the two components showed a synergistic effect on antifungals (Test Example 1). In addition, as a result of application to cosmetic compositions of various formulations, it was found that phenoxyethanol and ethylparaphene, which are widely used as preservatives for cosmetics in the past, exhibited remarkably higher antifungal and antibacterial activity than the negative control, , Exhibited superior antibacterial activity and exhibited equivalent or higher antifungal activity (Test Example 2). Furthermore, as a result of the skin irritation test on the preservative according to the present invention, the skin irritation index was about 14 times lower than that of the combination of methylparaben and phenoxyethanol (Test Example 3) As a result of the skin irritation test on the applied cosmetic formulation, the degree of irritation was remarkably lower than that of the formulation containing both phenoxyethanol and ethylparaphene, so that it was confirmed that it can be safely applied to the skin (Test Example 4).

Because of the antioxidative effect of tyrosol and chervicol contained in the preservative according to the present invention, in addition to the antiseptic effect due to the antimicrobial activity, the use of the preservative as a skin external agent is very important in that it can delay the oxidation of the external preparation for skin have.

The preservative for external preparation for skin according to the present invention may be prepared in the form of a mixed powder of tyrosol and chive call combination or may be manufactured and distributed in the form of a mixed powder mixed with a carrier such as a diluent if necessary, May be purchased for the manufacture of pharmaceutical preparations for external application and used as a preservative. The preparation of the mixed powder can be appropriately carried out using known knowledge and a person having ordinary skill in the art.

Another aspect of the present invention provides a cosmetic composition comprising the preservative for external preparation for skin.

The above-mentioned cosmetic composition can be provided as a cosmetic composition having high preservability and safety by containing the preservative for external preparation for skin. The content of the preservative for external preparation for skin used in the cosmetic composition is not particularly limited as long as a desired preservative force can be secured, and it can be appropriately determined by those skilled in the art depending on the desired degree of preservative power. For example, 0.01 to 20% by weight based on the cosmetic composition. Specifically, it may be about 0.1 to 10% by weight, more specifically about 0.1 to 5% by weight, and more specifically about 0.1 to 3% by weight based on the cosmetic composition.

The cosmetic composition may be any formulation known as a cosmetic composition and may be in the form of a skin, emulsion, cream, sunscreen, foundation, essence, gel, pack, mask pack, foam cleanser, body cleanser, But is not limited to, a single formulation selected from the group consisting of shampoo, rinse, soap, corrective agent, hair dye, hair cream, hair styling gel, lubricant, toothpaste and wet tissue.

Another aspect of the present invention provides a pharmaceutical composition for external application for skin comprising the preservative for external preparation for skin.

The pharmaceutical composition for external application for skin can be provided as a pharmaceutical composition which can be applied as an external preparation to skin having high preservation power and safety by containing preservative for external preparation for skin. The content of the preservative for external preparation for skin used in the pharmaceutical composition for external application for skin is not particularly limited as long as a desired preserving ability can be secured and can be suitably determined by those skilled in the art depending on the desired degree of preserving power. For example, about 0.01 to 20% by weight with respect to the pharmaceutical composition for external application for skin. Specifically, it may be about 0.1 to 10% by weight, more specifically about 0.1 to 5% by weight, and more specifically about 0.1 to 3% by weight based on the pharmaceutical composition for external application for skin.

The pharmaceutical composition for external application for skin may be any formulation known as an external preparation for skin, and may be, for example, a warning agent, a liniment agent, an ointment agent, a pasta agent, a cataplasma agent, a suspension agent, an emulsion, a rosophage agent, Suppositories, and suppositories. However, the present invention is not limited thereto.

The pharmaceutical composition for external application for skin may be for systemic action of the active ingredient by skin application or for local action of the active ingredient by skin application. In one embodiment, the pharmaceutical composition is for topical action of the active ingredient by skin application.

The cosmetic composition and the pharmaceutical composition for external application for skin may further contain various known additives in addition to the preservative for external preparation for skin as long as the effect of the preservative for external preparation for skin is not impaired according to the formulation. May further comprise additives selected from the group consisting of carriers, emulsifiers, moisturizers, skin conditioners, surfactants, chelating agents, antioxidants, bactericides, stabilizers, and any combination thereof.

Examples of the carrier include an animal fiber, a plant fiber, a wax, a paraffin, a starch, a tragacanth, a cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, lactose, silica, aluminum hydroxide, calcium silicate, Amide powder, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyleneglycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol, liquid diluent, ethoxylated isostearyl alcohol, Polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth, aliphatic alcohol sulfates, aliphatic alcohol ether sulfates, sulfosuccinic acid monoesters, Thionate, Aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolenic derivatives, or ethoxylated glycerol fatty acid esters, etc. But is not limited thereto.

Examples of the emulsifying agent include liquid paraffin, cetyl octanoate, stearic acid, and the like, but are not limited thereto.

Examples of the moisturizing agent include, but are not limited to, glycerin, glyceryl stearate and the like.

Examples of the skin conditioner include, but are not limited to, sarisplethicone, dimethicone, and the like.

Examples of the surfactant include cetostearyl alcohol, triethanolamine, carboxyvinyl polymer, and the like, but are not limited thereto.

Examples of the chelating agent include sodium ethylenediaminetetraacetate (EDTA), alpha -hydroxy fatty acid, lactoferrin, alpha -hydroxy acid, citric acid, lactic acid, malic acid, bilirubin, biliverdin, no.

Examples of the antioxidant include butylhydroxyanisole, dibutylhydroxytoluene, and propyl gallate, but are not limited thereto.

In addition, the cosmetic composition and the pharmaceutical composition may contain, as a possible component, a preservative component, an emollient, an organic and inorganic pigment, an organic powder, an ultraviolet absorber, a pH adjuster, an alcohol, a coloring matter, a perfume, a blood circulation accelerator, .

Another aspect of the present invention provides a method for producing an external preparation for skin comprising adding a preservative for the external preparation for skin as a preservative.

Details of the method for producing the external preparation for skin can be applied to the preservative for external preparation for skin, the cosmetic composition, and the pharmaceutical composition for external application for skin according to one aspect of the present invention.

In one embodiment, the external preparation for skin is a cosmetic composition or a pharmaceutical composition for external application for skin.

The preservative for external preparation for skin may be added in an amount of about 0.01 to 20% by weight based on the cosmetic composition or the pharmaceutical composition for external application for skin.

Hereinafter, the present invention will be described in detail based on the following examples. However, the following examples are intended to illustrate the present invention, but the scope of the present invention is not limited thereto.

[Abbreviation Description]

1,3-BG: 1,3-butylene glycol

Test Example  1: Antimicrobial activity test

For the antibacterial activity test, the preservatives of Examples 1 to 6 were prepared by combining tyrosol, chbarcor, and 1,3-BG according to the contents shown in Table 1 below and adding water to 100%. 1,3-BG was used as a solubilizing agent for dissolution of affinity chrysanthemum callus.

(ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Candida albicans (ATCC 10231), and Anispergillus strains prepared in Examples 1 to 6 Nitrogen (ATCC 16404), yeast, and fungi were measured.

First, samples of various concentrations (0.01 to 10%) prepared by diluting 10% of each test substance to 1/2 of 1/2 were prepared and added to 10 ml of the liquid culture medium prepared by adding the sample to the tryptic soy medium (TSB) The bacterium, yeast, and fungus were inoculated at a concentration of 10 ^{5 to 7} / ml, cultured at 32 ° C for 24 hours and poured into a plate to remove the bacteria, yeast, and fungus The minimum growth inhibitory concentration (MIC) was defined as the concentration at which the number of bacteria in the initial strain inoculated was significantly inhibited. The results are shown in Table 2 below.

For comparison, MICs were measured in the same manner as above except that thiolsole, chavicol, and 1,3-BG were treated alone, and the results are shown in Table 2 (unit: wt%).

As shown in Table 2 above, tyrosol alone has an efficacy of 2.0% or less in bacteria, but it is confirmed that a very high concentration is required for yeast and mold. However, the preservatives combined with trace amounts of chrysanthemum showed a significantly lower MIC concentration. Therefore, the preservative combined with tyrosol and chibicol has a synergistic effect on the inhibition of yeast and fungi, and has both antibacterial and antifungal activity, and has a preservative effect even in a small amount of use.

Test Example  2: Preparation of cosmetic composition and Buoyancy  exam

(One) Emulsion Buoyancy  exam

The emulsified formulations were prepared as shown in Table 3 using a composition prepared by mixing Tyrosol and Chibicol at a weight ratio of 1.0: 0.08. Comparative Example 1 was also prepared as shown in Table 3, except that no chemical preservative was used in the preparation of Comparative Example 1, and Comparative Example 2 used parabens and phenoxyethanol as chemical preservatives.

The buoyant force was measured on the above Example 7 and compared with Comparative Examples 1 and 2. First, a bacterial suspension of Escherichia coli (ATCC 8739), Staphylococcus aureus (ATCC 6538), and Pseudomonas aeruginosa (ATCC 99027) was added to 50 g of the cosmetic composition of Example 7 and Comparative Examples 1 and 2, The initial concentration was 10 ⁶ cfu (colony forming unit) / g or more. Then, 1 g of each cosmetic composition was taken at intervals of 0 day, 7 day, 14 day, 21 day, and 28 day while culturing in a thermostat at 30 ~ 32 캜 for 4 weeks.

In addition, the fungus was added to an initial concentration of 10 ⁵ cfu / g or more per each sample, and the mixture was mixed at an interval of 7 days at 25 ° C in a thermostatic chamber. The number of viable cell counts of yeasts, absence of swelling, and hyphae and spore formation on the surface of the sample were observed. The results are shown in Table 4.

(2) Non alcohol Of the skin formulations Buoyancy  exam

0.0 > Tylosol < / RTI > and Chibicol at a weight ratio of 1.0: 0.08 was used to prepare a non-alcohol skin formulation as shown in Table 5. Comparative Example 3 was also prepared as shown in Table 5, except that no chemical preservative was used in the preparation of Comparative Example 3, and Comparative Example 4 used parabens and phenoxyethanol as chemical preservatives.

The repelling force of Example 8 and Comparative Examples 3 and 4 was evaluated, and the results are shown in Table 6 below. The evaluation of the buoyant force was carried out in the same manner as in Example 7 and Comparative Examples 1 and 2.

(3) Creamy Buoyancy  exam

The cream formulation was prepared as shown in Table 7 using a composition prepared by mixing Tyrosol and Chibicol at a weight ratio of 1.0: 0.08. Comparative Example 5 was also prepared as shown in Table 7, except that no chemical preservative was used in the preparation of Comparative Example 5, and Comparative Example 6 used parabens and phenoxyethanol as chemical preservatives.

The buoyant forces of Example 9 and Comparative Examples 5 and 6 were evaluated, and the results are shown in Table 8 below. The evaluation of the buoyant force was carried out in the same manner as in Example 7 and Comparative Examples 1 and 2.

(4) Mask packs  Formulation Buoyancy  exam

Thiolsole and chibicol at a weight ratio of 1.0: 0.08 was used to prepare a mask pack dosage form as shown in Table 9. Comparative Example 7 was also prepared as shown in Table 9, except that no chemical preservative was used in the preparation of Comparative Example 7, and Comparative Example 8 used parabens and phenoxyethanol as chemical preservatives.

The buoyant forces of Example 10 and Comparative Examples 7 and 8 were evaluated, and the results are shown in Table 10 below. The evaluation of the buoyant force was carried out in the same manner as in Example 7 and Comparative Examples 1 and 2.

(5) Shampoo formulations Buoyancy  exam

A shampoo formulation was prepared as shown in Table 11 using a composition prepared by mixing Tyrosol and Chibicol at a weight ratio of 1.0: 0.08. Comparative Example 9 was also prepared as shown in Table 11, except that no chemical preservative was used in the preparation of Comparative Example 9, and Comparative Example 10 was using parabens and phenoxyethanol as chemical preservatives.

The buoyant forces of Example 11 and Comparative Examples 9 and 10 were evaluated, and the results are shown in Table 12 below. The evaluation of the buoyant force was carried out in the same manner as in Example 7 and Comparative Examples 1 and 2.

(6) Wet tissue formulation Buoyancy  exam

Tyrosol and chibicol at a weight ratio of 1.0: 0.08 was used to prepare a wet tissue formulation as shown in Table 13. Comparative Example 11 was also prepared as shown in Table 13, except that no chemical preservative was used in the preparation of Comparative Example 11, and Comparative Example 12 used parabens and phenoxyethanol as chemical preservatives.

The flotation forces of Example 12 and Comparative Examples 11 and 12 were evaluated, and the results are shown in Table 14 below. The evaluation of the buoyant force was carried out in the same manner as in Example 7 and Comparative Examples 1 and 2.

According to the results of the buoyancy tests of Examples 8 to 12, all of the antibacterial and antifungal activities were significantly superior to those of the negative control group, and the antibacterial activity and the antifungal activity were equivalent to those of the positive control group.

Test Example  3: skin irritation test

To confirm skin irritation, a preservative for external preparation for skin was prepared according to the composition shown in Table 15 below (Unit: wt%).

The patch was attached to the upper part of the subject's back, and 20 [mu] l of the 25% test composition was applied using IQ chamber chemo technique (Sweden). The first reading was tested 30 minutes after removing the patch, and the second reading was performed after 24 hours. To determine the intensity of the skin irritation of the samples, weights were assigned according to the degree of positive skin reaction, and the primary cutaneous irritation index (PCI) was calculated according to the following equation 1 to determine skin irritation Respectively.

The results are shown in Table 15 below.

[Equation 1]

As shown in Table 15, the skin irritation index was about 14 times lower than that of Example 13 containing a combination of tyrosine and chervis call and Comparative Example 13 containing methylparaben and phenoxyethanol mainly used in existing cosmetic products It was confirmed that the preservative for external preparation for skin according to the present invention can be safely applied to the skin.

As a result, the preservative for external preparations for skin according to the present invention is excellent in antibacterial activity including all antibacterial and antifungal agents, and has good usability, and can be used as a preservative for external preparations for skin without causing toxicity, skin irritation, irritation, It was confirmed that there is no. Therefore, the preservative for external preparations for skin according to the present invention has safety and efficacy, and can be very useful as a preservative for external preparations for skin including cosmetic compositions and the like.

Test Example  4: Irritability  exam

Twenty panelists were randomly assigned 1.5 ml of each of the samples of Example 10 and Comparative Example 8 by randomly changing the sides of the face nose and the ball area to apply to the skin, The stimuli were evaluated according to the evaluation criteria according to Table 16, and the results are shown in Table 17 below.

As shown in Table 17, it was confirmed that the composition of Example 10 showed up to 10 times or less the degree of irritation such as hotness and hot flashes than that of Comparative Example 8, so that it can be safely applied to skin without causing irritation .

The present invention has been described with reference to the preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the above-described embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (15)

A combination of tyrosol and chibi call,
Wherein said tyrosol and chibicol are contained in a weight ratio of 1 to 4.0: 0.04 to 0.08. The preservative for external use for skin according to claim 1, wherein the tyrosol and chibicol are contained in a weight ratio of 1 to 2.0: 0.06 to 0.08. The method of claim 1, wherein the tyrosol is selected from Ligustrum lucidum , Olea < / RTI > europaea , Plantago major, and any combination thereof. The method according to claim 1, wherein the call is a fare Agastache rugosa , Alpinia galanga , pineapple comosus , cinnamomum aromaticum , Melia azedarach , Ocimum basilicum , Origanum majorana , Pimenta dioica , Pimenta racemosa , Pimenta dioica , Piper betel, Syzygium aromaticum , Tagetes lucida , Zingiber wherein the preservative is derived from a herbal medicine selected from the group consisting of palm oil , officinale , and any combination thereof. The preservative for external preparation for skin according to claim 1, which is in the form of a powder comprising a combination of tyrosine and chive call. A cosmetic composition comprising the preservative for external preparation for skin according to any one of claims 1 to 5. The cosmetic composition according to claim 6, wherein the preservative for external preparation for skin is present in an amount of 0.01 to 20% by weight based on the cosmetic composition. The cosmetic composition according to claim 7, wherein the cosmetic composition is at least one selected from the group consisting of skin, emulsion, cream, sunscreen, foundation, essence, gel, pack, mask pack, foam cleanser, body cleanser, softener, eyeliner, shampoo, , A hair cream, a hair styling gel, a lubricant, a toothpaste, and a wet tissue. A pharmaceutical composition for external application for skin comprising the preservative for external preparation for skin according to any one of claims 1 to 5. [Claim 11] The pharmaceutical composition for external application for skin according to claim 9, wherein the preservative for external preparation for skin is present in an amount of 0.01 to 20% by weight based on the total amount of the composition. [Claim 10] The pharmaceutical composition according to claim 10, wherein the pharmaceutical composition is one selected from the group consisting of a warning agent, a liniment agent, an ointment agent, a pasta agent, a cataplasma agent, a suspending agent, an emulsion, a rosophage agent, an aerosol agent, A pharmaceutical composition for external application to skin. 12. The pharmaceutical composition according to claim 11, wherein the pharmaceutical composition is for systemic action or local action. A method for producing an external preparation for skin, which comprises using a preservative for external preparation for skin according to any one of claims 1 to 5 as a preservative. [14] The method according to claim 13, wherein the external preparation for skin is a cosmetic composition or a pharmaceutical composition for external application to skin. [14] The method according to claim 13, wherein the preservative is used in an amount of 0.01 to 20% by weight based on the cosmetic composition or the pharmaceutical composition for topical administration.