KR101945987B1 - A preservative comprising tyrosol 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 external application for skin comprising tyrosol, glyceryl caprylate and pentylene glycol, and to a cosmetic and a pharmaceutical composition containing the same. The preservative for external application for skin according to one aspect is not limited in application as an aqueous agent, since crystals are not precipitated when used as an aqueous agent thereby being safe and effective. Furthermore, the preservative does not cause toxicity, skin irritation, and allergy as in chemical preservatives such as parabens, and thus can be used safely. In addition, the preservative has preservative efficacy including remarkably excellent antimicrobial activity compared with conventional preservatives. Accordingly, by using the preservative for external application for skin, the cosmetic and the pharmaceutical composition, which is an aqueous agent as well as has excellent preservative efficacy and safety, can be produced.

Description

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

A preservative for external preparation for skin, a cosmetic composition containing the same, and a pharmaceutical composition.

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 preservatives (sodium p-hydroxybenzoate), imidazolidinyl ureas, and phenoxyethanol. These preservatives are highly preservative because of their high antimicrobial 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.

As a part of this research, researches have been conducted on preservatives for external preparations for skin using diols known to have antibacterial activity. Patent Document 1 discloses a three-way antimicrobial composition acting synergistically; 2-phenoxyethanol; And mixtures comprising at least two different alkanediols selected from the group consisting of 1,2-decanediol, 1,2-octanediol, 1,2-hexanediol, and 1,2-pentanediol. However, the above-mentioned ternary mixture also has toxicity, skin irritation, or allergy.

On the other hand, tyrosol is a substance produced in tyrosine by the action of yeast during alcohol fermentation of sugar. Non-Patent Document 1 refers to the antioxidative effect of tyrosol. However, there is no research to apply tyrosol to preservatives, cosmetic compositions, and pharmaceutical compositions for external application for skin. In particular, thyrosol exists in a crystalline form, which is a solubilization formulation containing water as a main solvent, and is not well dissolved in production, and crystals are precipitated, which limits the application of the solubilized formulation in the field of cosmetics.

Korean Patent Publication No. 2013-0049729

 Giovannini C, Straface E, Modesti D, Coni E, Cantaforae, De Vincenzi M, Malorni W, Masella R (1999). "Tyrosol, the major olive oil biophenol, protects against oxidized-LDL-induced injury in Caco-2 cells". J. Nutr. 129 (7): 1269-1277.

One aspect is the use of tyrosols of formula 1, or salts thereof, which are cosmetically or pharmaceutically acceptable

[Chemical Formula 1]

; 및

; And

And a preservative for external preparation for skin comprising pentylene glycol.

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

Another aspect provides a pharmaceutical composition for an external preparation for skin comprising the preservative for the external preparation for skin.

Another aspect provides a method for producing an external preparation for skin, which comprises using the preservative for external preparation for skin as a preservative.

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. 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.

&Quot; Antibacterial " means resistance to all contaminating microorganisms such as bacteria, fungi and yeast. &Quot; Antimicrobial activity " means a defense against these contaminating microorganisms. It is a concept that includes anti-microbial power.

"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 inventors of the present invention have found that when a crystal is not precipitated and is stable and does not contain a chemical preservative such as parabens and the like, it is not accompanied by irritation and the like even for a user having extremely sensitive skin. Were studied for the preservatives for external skin preparations.

As a result, a preservative for external preparation for skin comprising a combination of tyrosol and decanediol, or a combination of tyrosol and caprylyl glycol has been proposed as a preservative for external preparation for skin including a combination of tyrosol and pentylene glycol Can be stably prepared as a solubilized formulation without precipitation of crystals. In addition, the preservative for external preparation for skin, which comprises a combination of tyrosol, glyceryl caprylate and pentylene glycol, has a synergistic antibacterial and retention ability as compared with the case of using tyrosol, glyceryl caprylate or pentylene glycol alone, It was found that not only is the flotation power remarkably superior to the conventional parabens preservative but also the skin irritation is remarkably low.

Accordingly, one aspect of the present invention is a cosmetic or pharmaceutical acceptable salt thereof,

[Chemical Formula 1]

; 및

; And

And a preservative for external preparation for skin comprising pentylene glycol.

The term "tyrosol" is used interchangeably with "4- (2-hydroxyethyl) phenol" and may include p -tyrosol and o -tyrosol. In one embodiment, the tyrosol may be p -thyrosine.

The tyrosol may include a tyrosol derivative having antibacterial activity, retention, and / or repellency similar to tyrosine.

The tyrosol can be obtained by a person skilled in the art and known in the art. In one embodiment, the tyrosol may be contained in olive oil or argan oil.

The proportion of each component contained in the preservative for skin external preparation can be varied depending on the specific compound of each component and includes any proportion that exhibits effective antibacterial activity.

In one embodiment, the preservative for external preparation for skin may contain the above-mentioned tyrosol and pentylene glycol in a weight ratio of 1: 9 to 4: 6. In another embodiment, the preservative for external preparation for skin may contain the tyrosol and pentylene glycol in a weight ratio of 2: 8 to 3: 7. When the weight ratio of tyrosol and pentylene glycol is 5: 5 or higher, the content of tyrosol is higher, crystal precipitation may occur.

The preservative for external preparation for skin may further comprise glyceryl caprylate. In one embodiment, the preservative for external preparation for skin is selected from the group consisting of tyrosol; Glyceryl caprylate; And pentylene glycol.

In one embodiment, the preservative for external preparations for skin may comprise tyrosol, glyceryl caprylate, and pentylene glycol in a weight ratio of about 0.1-1.0: 0.1-1.0: 0.1-1.0, more specifically about 0.1-1.0: 0.3: 0.1 to 0.2: 0.6 to 0.8. In another embodiment, the weight ratio of thyrosol, glyceryl caprylate, and pentylene glycol may be about 0.1: 0.3: 0.6. In another embodiment, the weight ratio of thyrosol, glyceryl caprylate, and pentylene glycol may be about 0.2: 0.2: 0.6.

As a result of the test, a combination of tyrosol and decanediol, a combination of tyrosol and caprylyl glycol resulted in crystal precipitation, whereas a combination of tyrosol and pentylene glycol showed favorable application to cosmetic formulations since crystal precipitation did not occur ( See Test Example 1). Further, compared with the case where a composition comprising a combination of tyrosine, glyceryl caprylate, and pentylene glycol according to one embodiment of the present invention is treated with tyrosol, glyceryl caprylate, or pentylene glycol alone It was confirmed that it exhibits excellent antibacterial activity at a significantly low concentration (see Test Example 2). In addition, cosmetic compositions containing a combination of tyrosol, glyceryl caprylate, and pentylene glycol were found to have remarkably excellent buoyancy as compared with the conventional cosmetic preservatives such as ethyl paraben and phenoxyethanol (Test Example 3). In addition, the composition comprising a combination of tyrosine, glyceryl caprylate, and pentylene glycol according to an embodiment of the present invention is more effective than the comparative example including methylparaben and phenoxyethanol, which are mainly used in existing cosmetic products, The index was found to be at least 7 times lower than it was found to be safely applied to the skin (see Test Example 4).

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. In one embodiment, the preservative for external preparation for skin may be included in an amount of 0.01 to 10% by weight, 0.1 to 10% by weight, 0.1 to 5% by weight, or 0.1 to 2% by weight based on the total weight of the cosmetic composition.

The cosmetic composition may be any formulation known as a cosmetic composition and may be, for example, 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 a liner, a shampoo, a rinse, a soap, a correcting agent, a hair dye, a hair cream, a hair styling gel, a lubricant, a toothpaste and a 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, the preservative for external preparation for skin may be contained in an amount of 0.01 to 10% by weight, 0.1 to 10% by weight, 0.1 to 5% by weight, or 0.1 to 2% by weight based on the total weight of 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 suspending agent, an emulsion, a rosophage agent, And suppositories, but 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, poly 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 emulsifier 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 using the preservative for 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 may be a cosmetic composition or a pharmaceutical composition for external application for skin.

The preservative for external preparation for skin may be used in an amount of 0.01 to 10% by weight based on the cosmetic composition or the pharmaceutical composition for external application for skin.

Preservatives for external preparations for skin according to one aspect can be stable and exhibit their effects sufficiently without precipitation of crystals when used in aqueous preparations, so that application to aqueous preparations is not limited. In addition, it can be safely used because it does not cause toxicity, skin irritation, and allergy as in a chemical preservative such as parabens. In addition, it has a preservative ability that includes a remarkably excellent antibacterial activity as compared with conventional preservatives. Accordingly, the cosmetic composition and the pharmaceutical composition, which are water-based preparations, can be prepared by using the preservative for external preparation for skin as well as preserving power and safety.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Test Example 1: Preparation of preservative and stability test

Preservatives for external preparations for skin were prepared according to the ingredients and contents shown in Table 1 below.

Ingredients (Unit: wt%) Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Tyrosol 20 30 50 20 30 50 20 30 50 Pentylene glycol 80 70 50 Decanediol 80 70 50 Caprylyl glycol 80 70 50 Crystallization X X O O O O O O O

As shown in Table 1, the crystal precipitation occurred in the combination of tyrosol and decanediol (Comparative Examples 1 to 3), tyrosol and caprylyl glycol (Comparative Examples 4 to 6), whereas Examples 1 and 2 2 showed that the combination of tyrosol and pentylene glycol did not cause crystal precipitation and thus was convenient for cosmetic formulations.

Test Example 2: Preparation of preservative and test for antibacterial activity

For comparison, Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Anisugaruzumi strain The antimicrobial activity against bacteria, yeast and fungi such as Snigger (ATCC 16404) and Candida albicans (ATCC 10231) was measured.

Specifically, samples of various concentrations (0.01 to 10%) prepared by diluting 10% of each test substance up to 12 steps in 1/2 were prepared and added to 10 ml of a liquid culture medium prepared by adding the samples to a tryptic soy medium (TSB) , The bacteria and yeast were inoculated at a concentration of 10 ⁶ / ml and cultured at 32 ° C for 24 hours. The minimum inhibitory concentration (MIC) was determined by observing the state of bacteria and yeast and the concentration at which the number of bacteria in the initial strain inoculated was remarkably inhibited. The results are shown in Table 2 below.

Test substance E. coli P. aeruginosa S. aureus C. albicans A. niger Tyrosol 2.0 2.0 2.5 <4 <4 Glyceryl caprylate 1.5 <3.0 1.5 1.0 2.0 Pentylene glycol 3.0 5.0 5.0 5.0 3.0

Based on the results of the antibacterial activity test in Table 2, a composition for external application for skin was prepared according to the ingredients and contents shown in Table 3 below.

Raw material name
(Unit: wt%) Example 4 5 6 7 8 Purified water To 100 To 100 To 100 To 100 To 100 Tyrosol 0.1 0.1 0.2 0.2 0.3 Glyceryl caprylate 0.1 0.2 0.1 0.2 0.1 Pentylene glycol 0.8 0.7 0.7 0.6 0.6

(ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Anispergillus niger (ATCC 16404) and Candida albicans (ATCC 10231) were tested for their antibacterial activity against bacteria, yeast and fungi.

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) Each of the bacteria and yeast was inoculated at a concentration of 10 ⁶ / ml and cultured at 32 ° C for 24 hours. The results are shown in Table 4 below, with the minimum inhibitory concentration (MIC) being the concentration at which the number of bacteria in the initial strain inoculated by observing the condition of bacteria and yeast was significantly inhibited.

Test substance E. coli P. aeruginosa S. aureus C. albicans A. niger Example 4 2.5 2.5 <3.0 <3.0 <3.0 Example 5 2.0 2.0 3.0 3.0 3.0 Example 6 2.0 1.8 2.5 <3.0 <3.0 Example 7 1.5 1.5 2.0 1.5 2.0 Example 8 1.8 1.5 2.0 2.0 2.0

As shown in Table 4, it was confirmed that the compositions according to Examples 4 to 8 exhibited excellent antibacterial activity at a significantly lower concentration than those treated with tyrosol, glyceryl caprylate, and pentylene glycol alone.

Test Example 3: Preparation of cosmetic composition and flotation test

(1) Buoyancy test of the emulsion

A cosmetic composition of an emulsion formulation was prepared as shown in Table 5 below using a preservative mixed with a preservative mixed at a weight ratio of 0.2: 0.2: 0.6 in a weight ratio of 0.1: 0.3: 0.6, with tyrosol, glyceryl caprylate and pentylene glycol Respectively. Comparative Formulation Example 1 did not use any chemical preservatives in the preparation, and Comparative Formulation Example 2 produced the emulsion formulations in the same way except that a combination of parabens and phenoxyethanol was used as the chemical preservative.

Ingredients (Unit: wt%) Formulation Example Comparative Formulation Example One 2 One 2 Purified water To 100 To 100 To 100 To 100 Carbomer 940 10 10 10 10 Polyacrylate-13 / Polyisobutene / Polysorbate 20 0.8 0.8 0.8 0.8 Butylene glycol 15 15 15 15 Piggy 40 Hydrogenate castor oil 0.8 0.8 0.8 0.8 Phenyl trimethicone One One One One L-arginine 0.16 0.16 0.16 0.16 Thiolsole, glyceryl caprylate and pentylene glycol (0.2: 0.2: 0.6) 2 Thiolsole, glyceryl caprylate and pentylene glycol (0.1: 0.3: 0.6) 2 Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant forces were measured on Formulation Examples 1 and 2 and compared with Comparative Formulation Examples 1 and 2. [

First, 50 g of the emulsion-type cosmetic composition was mixed with 50 ml of a solution of Escherichia coli (ATCC 8739), Staphylococcus aureus (ATCC 6538), and Pseudomonas aeruginosa (ATCC 99027) at an initial concentration of 10 ⁶ cfu Forming unit, 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 incubation temperature of 25 ° C for 7 days (ATCC 16404) and Candida albicans (ATCC 10231) The number of viable cells in yeast, the presence or absence of swelling, and the presence of hyphae and spores on the surface of the sample were observed. The evaluation method was based on the following criteria.

-: No spawning and mycelium spawning for 8 weeks and good

+: Molding on the wall or lid within 4 weeks

++: mending within 4 weeks and mold on part of the surface

+++: Mildew and mold on the entire surface within 4 weeks

The results are shown in Table 6 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 emulsion Formulation Example 1 1 x 10 ⁶ 0 0 0 0 - Formulation Example 2 1 x 10 ⁶ <100 <10 0 0 - Comparative Formulation Example 1 1 x 10 ⁶ 3.5 x 10 ⁵ 6.0 x 10 ⁵ 1.1 x 10 ⁶ 1.7 x 10 ⁶ +++ Comparative Formulation Example 2 1 x 10 ⁶ <100 <10 <100 <100 -

(2) Buoyancy test of body wash formulation

A cosmetic composition of a body whitening formulation was prepared as shown in Table 7 using a preservative mixed with a preservative mixed with thyrosol, glyceryl caprylate and pentylene glycol in a weight ratio of 0.2: 0.2: 0.6 in a weight ratio of 0.1: 0.3: 0.6 Respectively. Comparative Formulation Example 3 did not use any chemical preservatives during manufacture, and Comparative Formulation Example 4 produced the body wash formulation in the same way except that a combination of parabens and phenoxyethanol was used as the chemical preservative.

Ingredients (Unit: wt%) Formulation Example Comparative Formulation Example 3 4 3 4 Purified water To 100 To 100 To 100 To 100 Disodium iodide 0.1 0.1 0.1 0.1 Polyacrylate-13 / Polyisobutene / Polysorbate 20 8 8 8 8 Sodium laureth sulfate 9 9 9 9 SAGE 80 Sorbitan Laurate 15 15 15 15 Piggy 40 Hydrogenate castor oil 0.8 0.8 0.8 0.8 Cocoa isopropyl betaine 19 19 19 19 Sodium chloride 0.8 0.8 0.8 0.8 Thiolsole, glyceryl caprylate and pentylene glycol (0.2: 0.2: 0.6) 2 Thiolsole, glyceryl caprylate and pentylene glycol (0.1: 0.3: 0.6) 2 Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant forces were measured on Formulation Examples 3 and 4 and compared with Comparative Formulation Examples 3 and 4. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion formulation. The results are shown in Table 8 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 Body wash Formulation Example 3 1 x 10 ⁶ <10 0 0 0 - Formulation Example 4 1 x 10 ⁶ <10 <10 0 0 - Comparative Formulation Example 3 1 x 10 ⁶ 3.0 x 10 ⁵ 5.0 x 10 ⁵ 1.0 x 10 ⁶ 1.5 x 10 ⁶ +++ Comparative Formulation Example 4 1 x 10 ⁶ <100 <10 <10 <10 -

According to the results of the buoyancy test, the cosmetic composition comprising a combination of tyrosol, glyceryl caprylate, and pentylene glycol exhibited remarkable buoyancy as compared with the conventional cosmetic preservatives ethylparaben and phenoxyethanol .

Test Example 4: Preparation of preservative and skin irritation test

To confirm skin irritation, a preservative for external preparation for skin was prepared according to the composition shown in Table 9 below.

Patches were attached to the upper portion of the subject's back, and 20 μl of each test material was applied using IQ Chamberkomotechnik (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 9 below.

[Equation 1]

Test substance Composition (unit: wt%) Primary skin irritation index ^*
(P.C.I) Example 9 0.4% Tyrosol, 0.4% glyceryl caprylate and 1.2% pentylene glycol   0.00 Example 10 0.8% Tyrosol, 0.8% glyceryl caprylate and 2.4% pentylene glycol   0.02 Example 11 0.2% Tyrosol, 0.6% glyceryl caprylate and 1.2% pentylene glycol 0.02 Example 12 0.4% Tyrosol, 1.2% glyceryl caprylate and 2.4% pentylene glycol 0.11 Comparative Example 7 0.1% methylparaben in pentylene glycol, 1% phenoxyethanol containing 0.14 Comparative Example 8 A 5% aqueous solution of pentylene glycol (vehicle)   0.02 Primary skin irritation index ^*
0? PC I? 0.05; No irritant
0.05? PC I? 0.15; Slight irritant
0.15? PC I? 0.5; Moderate irritant
>0.5; Strong irritant

As shown in Table 9, Examples 9 to 11, which include a combination of tyrosol, glyceryl caprylate and pentylene glycol, were prepared in Comparative Example 7 containing methylparaben and phenoxyethanol, which are mainly used in existing cosmetic products The skin irritation index was at least 7 times lower than that of the control group. Also, in Example 12 in which the content of glyceryl caprylate in the combination of tyrosol, glyceryl caprylate, and pentylene glycol was 1.2% by weight or more, the skin irritation index was relatively higher than in the other examples, Respectively. Accordingly, it has been confirmed that the composition for external application for skin according to one embodiment of the present invention can be safely applied to skin.

From the above results, it can be concluded that the composition for external application for skin of the present invention is excellent in anti-buoyancy and antibacterial activity, and has good usability, and does not cause toxicity, skin irritation, irritation and allergy due to use of a chemical preservative. I could confirm that it was useful.

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 (14)

, Thiolsole of the following formula (1), or a cosmetically or pharmaceutically acceptable salt thereof
[Chemical Formula 1]

; And
Preservative for external preparation for skin comprising pentylene glycol. The preservative for external preparation for skin according to claim 1, which comprises tyrosole and pentylene glycol in a weight ratio of 1: 9 to 4: 6. The preservative for external application for skin according to claim 1, further comprising glyceryl caprylate. 4. The preservative for external use for skin according to claim 3, wherein the preservative comprises tyrosol, glyceryl caprylate, and pentylene glycol in a weight ratio of 0.1 to 1.0: 0.1 to 1.0: 0.1 to 1.0. The preservative for external use for skin according to claim 4, wherein the preservative contains tyrosol, glyceryl caprylate, and pentylene glycol in a weight ratio of 0.1 to 0.3: 0.1 to 0.2: 0.6 to 0.8. A cosmetic composition comprising the preservative for external preparation for skin according to any one of claims 1 to 5. [Claim 7] The cosmetic composition according to claim 6, wherein the preservative for external preparation for skin is contained in an amount of 0.01 to 10% by weight based on the total weight of the cosmetic composition. The cosmetic composition according to claim 6, wherein the cosmetic composition is at least one selected from the group consisting of a skin, an emulsion, a cream, a sunscreen, a foundation, an essence, a gel, a pack, a mask pack, a foam cleanser, a body cleanser, a softening longevity, an eyeliner, a 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 skin external preparation is contained in an amount of 0.01 to 10% by weight based on the total weight of the pharmaceutical composition for external application for skin. The pharmaceutical composition according to claim 9, 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 suspension agent, an oil agent, a rosophage agent, an aerosol agent, A pharmaceutical composition for external application. 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. [Claim 12] The method according to claim 12, wherein the external preparation for skin is a cosmetic composition or a pharmaceutical composition for external application to skin. [Claim 12] The method according to claim 12, wherein the preservative is used in an amount of 0.01 to 10% by weight based on the cosmetic composition or the pharmaceutical composition for external application for skin.