KR20230101482A - 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 external skin application containing a combination of propyl gallate and a specific diol as active ingredients, and a cosmetic composition and a pharmaceutical composition containing the same, which are used in combination with propyl gallate and a specific diol to prevent preservatives and A preservative for external application for skin, which not only exhibits a synergistic effect in antibacterial activity, is harmless to specific beneficial bacteria but specifically exhibits antiseptic and antibacterial activity against specific harmful bacteria, and has excellent formulation stability, and a cosmetic composition and pharmaceutical composition containing the same will be.

Description

A preservative for skin external application, and a cosmetic composition and a pharmaceutical composition comprising the same}

The present invention relates to a preservative for external skin preparation containing a combination of propyl gallate and a specific diol as active ingredients, and a cosmetic composition and a pharmaceutical composition containing the same.

Preservatives are essential for long-term maintenance of the quality of various product groups such as cosmetics, pharmaceuticals, quasi-drugs, household goods, and food products. In particular, they have relatively long shelf life and are mainly composed of oil or water. In the case of a cosmetic composition composed of amino acid derivatives and proteins, etc., and a pharmaceutical composition for external use on the skin, the use of a preservative is more essential.

Therefore, cosmetic compositions and pharmaceutical compositions for external use on the skin cannot avoid being contaminated by microorganisms due to contact with fingers or tools during use due to the nature of use accompanied by application to the skin as well as during the manufacturing process, improving the preservation of the product. It is common to add preservatives for this purpose. As such preservatives, parabens preservatives such as sodium paraoxybenzoate, imidazolidinyl urea, phenoxyethanol, and the like are widely used. Although these preservatives have high antimicrobial activity and have excellent preservative power, they are known to cause toxicity, skin irritation, and allergy. Therefore, a preservative for external application for skin that does not cause skin irritation and has a high preservative power has been developed, and there is a need to develop a preservative for external application for skin that is safe and has a superior preservative power.

As part of these studies, studies on preservatives for external use on the skin using diols known to have antibacterial activity have been conducted.

Patent Document 1 is a synergistically acting three-way antimicrobial mixture comprising 2-phenoxyethanol; and 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 ternary mixture also has disadvantages such as toxicity, skin irritation, and allergy.

Patent Document 2 discloses a composition for external application for skin containing ethylhexylglycerin and 1,2-octanediol, and additionally at least one of a wide variety of glycerol ethers other than the ethylhexylglycerin, or 1,2- A composition for external application for skin further comprising at least one of a very wide range of alkalidiols having 4 to 16 carbon atoms other than octanediol is listed, and disclosed as having a moisturizing effect as well as an antibacterial effect. However, although Patent Document 2 lists compositions for external application for skin in a wide variety of combinations, only a few of the compositions actually show their effects, and their effects are also not sufficient.

Therefore, there is a need for continuous research on more effective and safe preservatives for external skin preparations.

Propyl gallate has been generally used as an antioxidant in foods and cosmetics, but the antiseptic or antibacterial efficacy of a combination of propyl gallate and a specific diol is not known.

In this regard, Patent Document 3 discloses an antibacterial composition containing a mixture of octyl gallate and 1,2-alkane diol corresponding to alkyl gallates as an active ingredient, but the possibility of substitution with propyl gallate It is not disclosed at all, and whether propyl gallate and 1,2-alkane diol can selectively exhibit antibacterial activity against harmful bacteria without having a significant preservative effect and particularly harmful effects on beneficial bacteria when combined with propyl gallate and 1,2-alkane diol. are silent about it.

Korean Patent Publication No. 2013-0049729 US Patent Publication No. 2011/0218250 Korean Patent Registration No. 10-2024947

An object of the present invention is to provide a preservative for topical skin application with excellent antiseptic and antibacterial activity and high formulation stability.

Another object of the present invention is to provide a cosmetic composition containing the preservative for external skin application.

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

To achieve the above object, one aspect of the present invention is

propyl gallate, a pharmaceutically or cosmetically acceptable salt thereof, a hydrate thereof, or a solvate thereof; and

At least one diol selected from the group consisting of 1,3-propanediol, 1,3-butanediol, 1,2-hexanediol, dipropylene glycol and glyceryl caprylate

It provides a preservative for skin external application comprising a.

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

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

The preservative for skin external use according to the present invention not only exhibits a synergistic effect in preservative and antibacterial activity by using a combination of propyl gallate and a specific diol, but also exhibits antiseptic and antibacterial activity specific to specific harmful bacteria although harmless to specific beneficial bacteria. , It has excellent formulation stability. In addition, it is possible to provide a cosmetic composition and a pharmaceutical composition capable of enhancing skin safety and usability due to high antiseptic and antibacterial activity as well as high formulation stability by using such a preservative for external skin preparation.

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

All technical terms used in the present invention, unless defined otherwise, are used with the same meaning as commonly understood by one of ordinary skill in the art related to the present invention. In addition, although preferred methods or samples are described in this specification, those similar or equivalent thereto are also included in the scope of the present invention. The contents of all publications cited herein by reference are hereby incorporated by reference in their entirety.

In the present specification, "external skin preparation" is a concept encompassing the overall composition applied to the skin, and includes, for example, various cosmetics such as basic cosmetics, makeup cosmetics, and hair cosmetics; It is a concept that includes pharmaceutical compositions including pharmaceuticals and quasi-drugs such as ointments, creams, and lotions.

"Antibacterial" means resistance to all contaminating microorganisms such as bacteria, fungi, and yeast, "antibacterial power" means defense against these contaminating microorganisms, and "preservative power" means the ability to decompose due to contamination by microorganisms. It means defense against things, and it is a concept that includes antibacterial power.

"Preservative" means a substance that has preservative or antioxidant power to prevent product deterioration and maintain its original state for a long period of time, and "preservative power" means a defense that can prevent product from deterioration and maintain its original state for a long period of time. it means.

The present invention provides a preservative for external use for the skin that does not contain conventional chemical preservatives with strong stimuli such as parabens, and can secure preservative power including antibacterial activity without causing irritation even for users with extremely sensitive skin. .

Specifically, the present invention relates to propyl gallate, a pharmaceutically or cosmetically acceptable salt thereof, a hydrate thereof, or a solvate thereof; and at least one diol selected from the group consisting of 1,3-propanediol, 1,3-butanediol, 1,2-hexanediol, dipropylene glycol, and glyceryl caprylate.

If propyl gallate, a pharmaceutically or cosmetically acceptable salt thereof, a hydrate thereof, or a solvate thereof is contained alone, not only is it precipitated during long-term storage, but the antibacterial activity is also deteriorated, and if only diol is included, it is precipitated during long-term storage. However, since the antibacterial activity is reduced, it is difficult to obtain the desired level of antimicrobial and / or antiseptic activity with propyl gallate, a pharmaceutically or cosmetically acceptable salt thereof, a hydrate thereof, a solvate thereof, or a diol alone, but combining them When used, it is possible to obtain excellent antibacterial and/or antiseptic activity by a synergistic effect.

The propyl gallate is also called propyl 3,4,5-trihydroxybenzoate, and is an ester formed by condensation of gallic acid and propanol, with molecular formula C ₁₀ H ₁₂ O ₅ , The molecular weight is 212.2 g / mol, and the structure is shown in Formula 1 below.

[Formula 1]

In one embodiment of the present invention, the propyl gallate used as an active ingredient may be used in the form of a "pharmaceutically or cosmetically acceptable salt". The “pharmaceutically or cosmetically acceptable salt” of propyl gallate may include salts prepared by adding a base to propyl gallate. Additional salts that can be used to prepare the pharmaceutically or cosmetically acceptable salt include one or more salts selected from the group consisting of sodium, potassium, calcium, ammonium, magnesium, organic amino, etc., but are not limited thereto no.

In one embodiment of the present invention, the propyl gallate may exist in unsolvated form as well as solvated form including hydrate, ethanolate, etc. forms. The propyl gallate of the present invention may exist in crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.

In one embodiment of the present invention, “hydrate” means a compound to which water is bound, and is a broad concept that includes inclusion compounds in which there is no chemical bonding between water and the compound.

In one embodiment of the present invention, "solvate" refers to a higher order compound formed between molecules or ions of a solute and molecules or ions of a solvent.

In one embodiment of the present invention, the preservative for skin external application contains propyl gallate and diol in a weight ratio of preferably 15:85 to 35:65, more preferably 20:80 to 30:70, and even more preferably It may be included in a ratio of 30:70 to 35:65.

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

The cosmetic composition according to the present invention may be provided as a cosmetic composition having high preservative power, antibacterial activity, safety, stability and usability by including the preservative for external skin application. The content of the preservative for external skin application used in the cosmetic composition is not particularly limited as long as it can secure the desired preservative power, and can be appropriately determined by those skilled in the art according to the degree of the desired preservative power. For example, the preservative for external application for skin according to the present invention is about 0.01 to 20% by weight, preferably about 0.1 to 10% by weight, more preferably about 0.1 to 5% by weight, and even more preferably, based on the total weight of the cosmetic composition. Preferably it may be about 0.1 to 2% by weight.

The cosmetic composition according to the present invention may have any dosage form and is not particularly limited, for example, skin, emulsion, cream, sunscreen, foundation, essence, gel, pack, mask pack, foam cleanser, body cleanser, softening It may be one formulation selected from the group consisting of longevity, eyeliner, shampoo, rinse, soap, hairdressing agent, hair growth agent, hair cream, hair styling gel, lubricant, toothpaste, and wet tissue.

Another aspect of the present invention provides a pharmaceutical composition, specifically a pharmaceutical composition for topical administration, containing the preservative for external application to the skin.

The pharmaceutical composition according to the present invention may be provided as a pharmaceutical composition having high preservative power, antibacterial activity, safety, stability and usability by including the preservative for external skin application. The content of the preservative for external application on the skin used in the pharmaceutical composition is not particularly limited as long as it can secure the desired preservative power, and can be appropriately determined by those skilled in the art according to the degree of the desired preservative power. For example, the preservative for external application for skin according to the present invention is about 0.01 to 20% by weight, preferably about 0.1 to 10% by weight, more preferably about 0.1 to 5% by weight, based on the total weight of the pharmaceutical composition. Preferably it may be about 0.1 to 2% by weight.

The pharmaceutical composition according to the present invention may have any dosage form and is not particularly limited. It may be one formulation selected from the group consisting of je, and suppositories.

In addition to the preservative for external application for skin, the cosmetic composition and pharmaceutical composition may further include various known additives according to the desired formulation within a range that does not impair the effect of the preservative for external application for skin. According to one embodiment, the carrier , emulsifiers, moisturizers, skin conditioning agents, surfactants, chelating agents, antioxidants, bactericides, stabilizers, and any combination thereof.

Carriers that may be included in the cosmetic composition or pharmaceutical composition according to the present invention include animal fibers, plant fibers, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, Lactose, aluminum hydroxide, calcium silicate, polyamide powder, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol oil, glycerol aliphatic ester, polyethylene Glycols, liquid diluents, ethoxylated isostearyl alcohols, suspending agents such as polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, aliphatic alcohol sulfates, aliphatic alcohol ethers Sulfates, sulfosuccinic acid monoesters, isethionates, imidazolinium derivatives, methyl taurates, sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils. , linolin derivatives, or ethoxylated glycerol fatty acid esters, but are not limited thereto.

Examples of emulsifiers that may be included in the cosmetic composition or pharmaceutical composition according to the present invention include liquid paraffin, cetyloctanoate, and stearic acid, but are not limited thereto.

Moisturizers that may be included in the cosmetic composition or pharmaceutical composition according to the present invention include glycerin and glyceryl stearate, but are not limited thereto.

Examples of skin conditioning agents that may be included in the cosmetic composition or pharmaceutical composition according to the present invention include cyclomethicone and dimethicone, but are not limited thereto.

Examples of surfactants that may be included in the cosmetic composition or pharmaceutical composition according to the present invention include cetostearyl alcohol, triethanolamine, and carboxyvinyl polymer, but are not limited thereto.

Chelating agents that may be included in the cosmetic composition or pharmaceutical composition according to the present invention include sodium ethylenediaminetetraacetate (EDTA), α-hydroxy fatty acid, lactoferrin, α-hydroxy acid, citric acid, lactic acid, malic acid, bilirubin, bill Liverdin (biliverdin) and the like, but is not limited thereto.

Antioxidants that may be included in the cosmetic composition or pharmaceutical composition according to the present invention include butylhydroxyanisole, dibutylhydroxytoluene, and ethyl ferulate, but are not limited thereto.

In addition, as components that can be blended in the cosmetic composition or pharmaceutical composition according to the present invention, oil and fat components, emollients, organic and inorganic pigments, organic powders, ultraviolet absorbers, pH adjusters, alcohols, pigments, fragrances, blood circulation promoters, cooling agents, restrictions I have my back.

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

The details of the preparation method of the external skin preparation may be applied as described for the preservative, cosmetic composition, and pharmaceutical composition for external skin preparation according to one aspect of the present invention.

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

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

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

[Reference Example] Strains and culture conditions

The strains and their culture conditions used to evaluate the antiseptic and antibacterial activity of the present invention are as follows:

- Escherichia coli ATCC (American Type Culture Collection) 8739: TSB (tryptic soy broth; tryptic soy medium), 32 ° C.

- Staphylococcus aureus ATCC 6538: TSB, 32 ℃

- Candida albicans ( Candida albicans ) ATCC 10231: PDA (potato dextrose agar medium; potato agar medium), 25 ° C

- Aspergillus brasiliensis ( Aspergillus brasiliensis ) ATCC 16404: PDA, 25 ℃

[Test Example 1] Evaluation of antibacterial activity according to a specific combination ratio of propyl gallate and diol

In this test example, microorganisms, specifically bacteria (E. coli, Staphylococcus aureus), yeast (Candida albicans), and fungi (Aspergillus brasiliensis) according to a specific combination ratio of propyl gallate and diol Antibacterial activity was evaluated.

To this end, materials to be tested were first prepared with the compositions shown in Table 1 below. The prepared material was diluted to 2% in purified water, and serially diluted by 1/2 to prepare samples of various concentrations from 0.0125% to 2%. The microorganisms were inoculated at a concentration of 10 ⁶ cells/ml in 10 ml of a liquid culture medium prepared by adding the same to TSB or PDA, and then cultured at 32°C or 25°C for 24 hours. By observing the state of microorganisms, the concentration that significantly inhibits the number of bacteria of the initial strain inoculated was set as the minimum inhibitory concentration (MIC), and the results are shown in Table 1 below.

union fee
(by weight) Precipitation
(25℃) MIC (%, w/w) Escherichia coli Staphylococcus
aureus Candida
albicans Aspergillus
brasiliensis Example 1 Propyl Gallate: 1,3-propanediol
(15:85) X 2 2 One 2 Example 2 Propyl Gallate: 1,3-propanediol
(20:80) X 0.5 0.5 0.5 One Example 3 Propyl Gallate: 1,3-propanediol
(30:70) X 0.5 0.5 0.25 0.5 Example 4 Propyl Gallate: 1,3-propanediol
(35:65) X 0.25 0.25 0.25 0.5 Example 5 Propyl Gallate: 1,3-propanediol
(40:60) X 0.125 0.125 0.125 0.25 Comparative Example 1 propyl gallate O >4 >4 >4 >4 Comparative Example 2 Propyl Gallate: 1,3-propanediol
(10:90) X 2 2 2 >4 Comparative Example 3 Propyl Gallate: 1,3-propanediol
(52:48) O >4 >4 >4 >4 Comparative Example 4 1,3-propnaediol X >20 >20 >20 >20

As shown in Table 1, when propyl gallate was treated alone, not only was there a stability problem during long-term storage due to precipitation, but also the antibacterial activity was not high, and when 1,3-propanediol was treated alone, precipitation There was no problem, but the antibacterial activity was low. On the other hand, when propyl gallate and 1,3-propanediol were used in combination, excellent antibacterial activity was shown even at a remarkably low concentration, and it was confirmed that there was a significant synergistic effect.

In addition, even when propyl gallate and 1,3-propanediol were combined, as in Comparative Example 2, if the amount of propyl gallate relative to 1,3-propanediol was less than the appropriate range, the desired level of antibacterial activity could not be obtained. As in Example 3, if the amount of propyl gallate relative to 1,3-propanediol is greater than the appropriate range, precipitation problems may occur during long-term storage. It was confirmed that it is preferable to combine in an appropriate ratio.

[Test Example 2] Evaluation of antibacterial activity according to the combination of propyl gallate and a specific type of diol

In this test example, propyl gallate and specific bacteria (E. coli, Pseudomonas aeruginosa and Staphylococcus aureus), yeast (Candida albicans), and fungi (Aspergillus brasiliensis) Antibacterial activity was evaluated according to the combination of types of diols.

To this end, materials were first prepared with the compositions shown in Table 2 below. The prepared material was diluted to 2% in purified water, and serially diluted by 1/2 to prepare samples of various concentrations from 0.0125% to 2%. The microorganisms were inoculated at a concentration of 10 ⁶ /ml in 10 ml of a liquid culture medium prepared by adding the same to TSB or PDA, and then cultured at 32°C or 25°C for 24 hours. By observing the state of microorganisms, the concentration that significantly inhibits the number of bacteria of the initial strain inoculated was set as the minimum growth inhibitory concentration (MIC), and the results are shown in Table 2 below.

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(by weight) Precipitation (25℃) MIC (%, w/w) Escherichia coli Staphylococcus
aureus Candida
albicans Aspergillus
brasiliensis Example 6 Propyl Gallate: 1,3-propanediol
(30:70) X 0.5 0.5 0.25 0.5 Example 7 Propyl Gallate: 1,3-Butanediol
(30:70) X 0.5 0.5 0.25 0.5 Example 8 Propyl Gallate: 1,2-hexanediol
(30:70) X 0.125 0.125 0.06 0.25 Example 9 Propyl Gallate: Dipropylene Glycol
(30:70) X 0.5 0.5 0.5 0.5 Example 10 Propyl Gallate: Glyceryl Caprylate
(30:70) X 0.125 0.125 0.06 0.125 Comparative Example 5 Propyl Gallate: Methylpropanediol
(30:70) X One One 2 >4 Comparative Example 6 Propyl Gallate: 1,2-pentanediol
(30:70) O >4 >4 >4 >4 Comparative Example 7 Propyl Gallate: 1,2-octanediol
(30:70) O >4 >4 >4 >4 Comparative Example 8 1,3-propanediol X >20 >20 >20 >20 Comparative Example 9 1,3-butanediol X >20 >20 >20 >20 Comparative Example 10 1,2-hexanediol X 2 2 2 4 Comparative Example 11 dipropylene glycol X >20 >20 >20 >20 Comparative Example 12 Glyceryl Caprylate X One One One 2 Comparative Example 13 Methyl Propanediol X >20 >20 >20 >20 Comparative Example 14 1,2-pentanediol X 8 8 8 16 Comparative Example 15 1,2-octanediol O 0.5 0.5 0.25 0.5

As shown in Table 2, when the diols were treated alone, the antibacterial activity was low, and in the case of 1,2-octanediol of Comparative Example 15, some antibacterial activity was shown, but precipitation was observed It was confirmed that this could affect the stability of the formulation. In addition, even when propyl gallate is combined with diols, it can be confirmed that the antibacterial activity varies greatly depending on the type, as shown in Examples 6 to 10 and Comparative Examples 5 to 7.

In addition, in the case of 1,2-pentanediol, precipitation was not observed when used alone, but precipitation was observed when used in combination with propyl gallate. I was able to confirm that it did.

[Test Example 3] Evaluation of preservative activity according to the combination of propyl gallate and a specific type of diol in a cosmetic composition

In this test example, propyl gall is applied to microorganisms, specifically bacteria (E. coli, Pseudomonas aeruginosa and Staphylococcus aureus), yeast (Candida albicans), and fungi (Aspergillus brasiliensis) in the cosmetic composition. The antiseptic activity according to the combination of rate and specific type of diol was evaluated.

To this end, first, a cosmetic composition containing the preservative for external application for skin of Examples 5 to 9 or Comparative Examples 5 to 7 was prepared with the composition shown in Table 3 below.

raw material name
(Unit: % by weight) formulation example One 2 3 4 5 comparison
Formulation example 1 comparison
Formulation example 2 comparison
Formulation example 3 Purified water UP TO 100 UP TO 100 UP TO 100 UP TO 100 UP TO 100 UP TO 100 UP TO 100 UP TO 100 Disodium EDT 0.02 0.02 0.02 0.02 0.02 0.02 0.02 0.02 glycerin 5 5 5 5 5 5 5 5 Glyceryl Stearate/PEG-100 Stearate One One One One One One One One caprylic/
capric triglyceride 5 5 5 5 5 5 5 5 sodium hyalunonate 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Polyacrylate-13/Polyisobutene/Polysorbate 20 One One One One One One One One polysorbate 60 2 2 2 2 2 2 2 2 squalane 3 3 3 3 3 3 3 3 phenyl trimethicone 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
skin
For external use
preservative Example 1 One - - - - - - - Example 2 - One - - - - - - Example 3 - - One - - - - - Example 4 - - - One - - - - Example 5 - - - - One - - - Comparative Example 1 - - - - - One - - Comparative Example 2 - - - - - - One - Comparative Example 3 - - - - - - - One

The preservative power of Formulation Examples 1 to 5 and Comparative Formulation Examples 1 to 3 was measured and compared. First, in 50 g of the cosmetic compositions of Formulation Examples 1 to 5 and Comparative Formulation Examples 1 to 3, bacterial solutions of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa were added to each sample at an initial concentration of 1.9 × 10 ⁶ cfu ( Colony forming unit (colony forming unit)/g or more was added and mixed. Then, 1 g of each cosmetic composition sample was taken on the 0th, 7th, 14th, 21st and 28th days at intervals of 7 days while culturing in a thermostat at 25 ° C for 4 weeks, and the number of viable cells was measured.

In addition, separately, the bacterial solution of Candida albicans and Aspergillus brasiliensis was added to the cosmetic compositions of Formulation Examples 1 to 5 and Comparative Formulation Examples 1 to 3 at an initial concentration of 10 ⁵ cfu / g or more, and then mixed. While culturing in a thermostat for 4 weeks at ℃, the presence or absence of off-odor and the presence or absence of hyphae and sporulation on the sample surface were observed at intervals of 7 days on days 0, 7, 14, 21 and 28.

The results are shown in Table 4 below.

Bacteria (cfu/g) fungi Day 0 Day 7 Day 14 Day 21 Day 28 Formulation example 1 2.3 × 10 ⁶ <1000 <10 <10 0 - Formulation Example 2 2.3 × 10 ⁶ <1000 <10 <10 0 - Formulation Example 3 2.3 × 10 ⁶ <10 0 0 0 - Formulation Example 4 2.3 × 10 ⁶ <1000 <100 <10 0 - Formulation Example 5 2.3 × 10 ⁶ <10 0 0 0 - Comparative Formulation Example 1 2.3 × 10 ⁶ <1000 <100 <10 0 ++ Comparative Formulation Example 2 2.3 × 10 ⁶ 1.4 × 10 ⁵ 2.0 × 10 ⁵ 2.1 × 10 ⁵ 3.0 × 10 ⁴ +++ Comparative Formulation Example 3 2.3 × 10 ⁶ 9.0 × 10 ⁸ 1.1 × 10 ⁶ 1.4 × 10 ⁵ 1.4 × 10 ⁵ ++

(-: Normal state without off-flavor, hyphae, and spores for 4 weeks;

+: fungi on container walls or lids within 4 weeks;

++: Occurrence of off-odor within 4 weeks and occurrence of fungi on a part of the sample surface;

+++: Occurrence of off-odor within 4 weeks and occurrence of fungus on the entire surface of the sample)

As shown in Table 4, Formulation Examples 1 to 5 according to the present invention exhibited very excellent antibacterial activity, but in the case of Comparative Formulation Examples 2 and 3, the antibacterial effect was insignificant, and in the case of Comparative Formulation Example 1 Compared to Formulation Examples 1 to 5, although the degree was lower, it was confirmed that the antibacterial effect was exhibited. However, while Formulation Examples 1 to 5 exhibit excellent antiseptic effects against yeast and fungi, it can be confirmed that all of Comparative Formulation Examples 1 to 3 showed off-odor and fungus development after a certain period of time.

[Test Example 4] Evaluation of antibacterial activity of the preservative according to the present invention against harmful bacteria and beneficial bacteria

In this test example, the antibacterial activity of the preservative according to the present invention against harmful bacteria and beneficial bacteria was evaluated.

Specifically, the strains and culture conditions used in this test example are as follows:

Harmful bacteria:

- Malassezia furfur ( Malassezia furfur ) ATCC 14521 (dandruff-causing bacteria): Leeming and Notman Agar, 32 ℃, aerobic conditions

- Trichophyton rubrum ( Trichophyton rubrum ) ATCC 28188 (athlete's foot causing bacteria): PDA, 25 ℃, aerobic conditions

Beneficial Bacteria:

- Lactobacillus plantarum ( Lactobacillus plantarum ) ATCC 14917 (lactic acid bacteria): MRS (De Man, Rogosa and Sharpe) medium, 32 ° C, anaerobic conditions

200 μl of the culture solution of the strain activated by culturing in a liquid medium was spread evenly on the plate medium with a sterile cotton swab to absorb the bacteria. Thereafter, wells were made on the surface of the medium with a sterilized 7 mm Pasteur pipette, and then 60 μl of each of the compositions described in Table 5 was injected and absorbed. Thereafter, the cells were cultured according to the culture conditions for each bacterium, and the diameter of the surrounding inhibition zone including the diameter of the well was measured.

The results are shown in Table 5 below.

harmful bacteria beneficial bacteria Malassezia Purpur trichophyton rubrum Lactobacillus Plantarum Propyl gallate : 1,3-propanediol = 30 : 70 + ++ - Propyl gallate : 1,3-butanediol = 30 : 70 + ++ - Propyl gallate : 1,2-hexanediol = 30 : 70 ++ +++ - Propyl Gallate : Dipropylene Glycol = 30 : 70 + ++ - Propyl Gallate: Glyceryl Caprylate =
30:70 ++ ++ -

(-: No antibacterial activity;

+: 7-19 mm;

++: 20-30 mm;

+++: > 30 mm)

As shown in Table 5, the preservative according to the present invention did not show antibacterial activity against beneficial bacteria, but showed significant antibacterial activity against harmful bacteria. It was confirmed that it exhibits antiseptic/antibacterial activity selectively against Pur and Trichophyton rubrum.

Claims (9)

propyl gallate, a pharmaceutically or cosmetically acceptable salt thereof, a hydrate thereof, or a solvate thereof; and
At least one diol selected from the group consisting of 1,3-propanediol, 1,3-butanediol, 1,2-hexanediol, dipropylene glycol and glyceryl caprylate
A preservative for external use on the skin comprising a. According to claim 1,
The propyl gallate, a pharmaceutically or cosmetically acceptable salt thereof, a hydrate thereof, or a solvate thereof; and diol in a weight ratio of 15:85 to 35:65. According to claim 1,
Characterized in that it does not exhibit antibacterial activity against beneficial bacteria including Lactobacillus plantarum while exhibiting antibacterial activity against harmful bacteria including Malassezia furfur and Trichophyton rubrum Phosphorus, skin preservative for external use. A cosmetic composition comprising the preservative for skin external application according to any one of claims 1 to 3. According to claim 4,
The cosmetic composition for the external application for the skin is included in an amount of 0.01 to 20% by weight based on the total weight of the cosmetic composition. According to claim 4,
The cosmetic composition is skin, emulsion, cream, sunscreen, foundation, essence, gel, pack, mask pack, foam cleanser, body cleanser, softening lotion, eyeliner, shampoo, conditioner, soap, hairdressing agent, hair conditioner, hair cream, hair A cosmetic composition selected from the group consisting of styling gels, lubricants, toothpaste and wet wipes. A pharmaceutical composition comprising the preservative for skin external application according to any one of claims 1 to 3. According to claim 7,
The preservative for external application for the skin is included in an amount of 0.01 to 20% by weight based on the total weight of the pharmaceutical composition. According to claim 7,
The pharmaceutical composition is selected from the group consisting of warning agent, liniment agent, ointment agent, pasta agent, cataplasma agent, suspension agent, emulsion agent, lotion agent, aerosol agent, and suppository, a pharmaceutical composition.