KR101702648B1

KR101702648B1 - A preservative for skin external application, and a cosmetic composition and a pharmaceutical composition comprising the same

Info

Publication number: KR101702648B1
Application number: KR1020160057134A
Authority: KR
Inventors: 조윤기; 양한용; 조명찬
Original assignee: 주식회사 엑티브온
Priority date: 2016-05-10
Filing date: 2016-05-10
Publication date: 2017-02-03
Also published as: WO2017195961A1; CN107592809A

Abstract

One aspect of the present invention is an acetophenone derivative of Formula 1; 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, 1,6-hexanediol (1, , 6-hexanediol, 1,8-octanediol, and any combination thereof; And a preservative for external preparation for skin comprising dipropylene glycol; And a preservative for the external preparation for skin, and a pharmaceutical composition for external preparation for skin.

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 preservative, an antimicrobial agent, a preservative, an antiseptic such as a preservative such as a paraben, And a preservative for a new skin external preparation which is safe and 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 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.

Patent Document 2 discloses an antimicrobial composition for an external preparation for skin comprising a combination of an acetophenone derivative and an alkane diol conventionally known as antimicrobial agents, respectively, as an antimicrobial composition. However, in the actual specification, it merely shows a synergistic antimicrobial effect on the combination of 4-hydroxyacetophenone as an acetophenone derivative and 1,2-hexanediol as an alkane diol. Further, there is a problem that the combination of the 4-hydroxyacetophenone and the 1,2-hexanediol is precipitated at the time of manufacturing a solubilized formulation using water as a main solvent, and its application as a solubilization formulation in the field of cosmetics may be limited .

Therefore, there is a need for continuous research on a skin preservative that is more effective and safe, and is not limited in its application as a solubilization formulation.

1. Korean Patent Publication No. 2013-0049729 2. Korean Patent Publication No. 2015-0127223

An object of the present invention is to provide a preservative for external preparation for skin.

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

It is still another object of the present invention to provide a pharmaceutical composition comprising the preservative for external preparation for skin.

It is still another object of the present invention 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 relates to an acetophenone derivative of the general formula (I) or a cosmetically or pharmaceutically acceptable salt thereof

[Chemical Formula 1]

(Wherein R ₁ represents hydrogen or methyl, and R ₂ represents hydrogen or hydroxy); And

A preservative for external application for skin comprising dipropylene glycol.

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 preserving agent for external preparation for skin which is excellent in preservation power and does not induce irritation to the skin and is very safe. In addition, since crystals are not precipitated when used in an aqueous preparation, the effect can be sufficiently exhibited, and application to an aqueous formulation is not limited. Therefore, according to one embodiment of the present invention, a cosmetic composition and a pharmaceutical composition, which are water-based preparations, can be prepared as well as high preservability and safety 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. 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 all contaminating microorganisms such as bacteria, fungi and yeast. "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 present inventors have conducted studies on a preservative for external preparation for skin, which is capable of securing a preservative force including antimicrobial activity remarkably superior to the conventional preservative without accompanying stimuli when used even for a user having extremely sensitive skin because of not containing a chemical preservative such as parabens Respectively.

As a result, it has been found that a preservative for external preparation for skin, which comprises a combination of an acetophenone derivative and dipropylene glycol, has a synergistic antibacterial and preservative ability compared to the case of using an acetophenone derivative or dipropylene glycol alone, Found that not only the buoyancy was significantly superior but also the skin irritation was remarkably low. In addition, a preservative for external preparation for skin, which comprises a combination of an acetophenone derivative, an alkane diol, and a dipropylene glycol, has a synergistic antibacterial and preservative effect compared to the case of using a combination of an acetophenone derivative and an alkane diol, , Which is remarkably superior in flotation power as compared with conventional parabens preservatives, and that skin irritation is remarkably low. In addition, in the conventional combination of acetophenone derivative and alkane diol, crystal is precipitated in a solubilized formulation containing water as a main solvent, while a preservative for external preparation for skin, which contains a combination of an acetophenone derivative and dipropylene glycol, And thus can be produced as a solubilized formulation.

Accordingly, one aspect of the present invention is

An acetophenone derivative represented by the following general formula (1) or a cosmetically or pharmacologically acceptable salt thereof

[Chemical Formula 1]

A preservative for external application for skin comprising dipropylene glycol.

The preservative for the external preparation for skin is selected from the group consisting of 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, An alkane diol selected from the group consisting of 1,6-hexanediol, 1,8-octanediol, and any combination thereof.

The acetophenone derivatives can be obtained by methods known to those skilled in the art. Both of the substituents OR < ₁ > and R < ₂ > may be present at ortho, meta, or para positions to the methylketo group.

The acetophenone

And any combination thereof.

The alkane diols may be selected from the group consisting of 1,2-octane diol, 1,2-hexane diol, 1,2-decane diol, and any combination thereof.

In one embodiment, the preservative for the external preparation for skin is

And hydroxyacetophenone selected from the group consisting of any combination thereof;

Alkane diols selected from the group consisting of 1,2-octane diol, 1,2-hexane diol, 1,2-decane diol, and any combination thereof; And

Dipropylene glycol.

In one embodiment, the preservative for external preparation for skin is 4-hydroxyacetophenone; 1,2-octanediol; And dipropylene glycol.

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.

The acetophenone derivative and dipropylene glycol may be contained in a weight ratio of about 0.01 to 10: 0.01 to 10, and more specifically about 0.1 to 0.6: 0.1 to 0.6 . In one embodiment, the preservative for topical dermatology may comprise acetophenone derivatives: and dipropylene glycol in a weight ratio of about 0.5: 0.5.

More preferably about 0.1 to about 0.6: 0.1 to about 0.5: 0.1 to about 0.6: 1, more preferably about 0.5 to about 5: 1, By weight . In one embodiment, the preservative for skin topical agents may comprise acetophenone derivatives: alkane diols: and dipropylene glycol in a weight ratio of about 0.3: 0.15: 0.55.

In one embodiment, the preservative for external preparation for skin may comprise 4-hydroxyacetophenone, 1,2-octanediol, and dipropylene glycol in a weight ratio of about 0.01 to 10: 0.01 to 10: 0.01 to 10, More specifically 0.1 to 0.6: 0.1 to 0.5: 0.1 to 0.6. In one embodiment, the 4-hydroxyacetophenone, 1,2-octanediol, and dipropylene glycol can be included in a weight ratio of about 0.3: 0.15: 0.55.

As a result, the antibacterial activity against bacteria and fungi was remarkably higher than that of each of the preservatives for external preparation for skin including acetophenone derivatives and dipropylene glycol. In addition, the preservative for external preparation for skin including acetophenone derivatives, alkane diols, and dipropylene glycol according to one embodiment of the present invention has remarkably higher antimicrobial activity against bacteria and fungi than the case of combining two of the above three components Respectively. In addition, it has a synergistic effect on the antibacterial effect against bacteria and fungi, as compared with the combination of acetophenone derivative and alkane diol and the case of dipropylene glycol alone.

In addition, while the combination of acetophenone derivative and alkane diol causes crystal precipitation in an aqueous solution, the preservative composition comprising a combination of acetophenone derivative and dipropylene glycol according to one embodiment of the present invention does not cause crystal precipitation in an aqueous solution It is possible to apply it as a solubilization formulation using water as a main solvent in the field of cosmetics (see Test Examples 1 and 2).

In addition, the preservative composition containing an acetophenone derivative and dipropylene glycol according to an embodiment of the present invention has a significantly lower skin irritation index than a combination of an acetophenone derivative and an alkanediol, And phenoxyethanol, and was found to be safely used without skin irritation (see Test Examples 3 and 4).

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 2% 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 2% 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]

4-HAP: 4-hydroxyacetophenone

DPG: dipropylene glycol

Test Example 1: Preparation of preservative and test for antibacterial activity

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

Raw material name
(Unit: wt%) Comparative Example 1 Example
One Example
2 Example 3 Example
4 Comparative Example
2 Comparative Example
3 Purified water To 100 To 100 To 100 To 100 To 100 To 100 To 100 4-HAP 0.5 0.5 0.5 0.3 0.3 - - 1,2-octanediol 0.5 - 0.2 0.2 0.15 0.5 0.4 DPG - 0.5 0.3 0.5 0.55 0.5 0.6 Crystallization ○ X ○ X X X X

(ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), and Candida albicans (ATCC 8739), which are the preservatives prepared in Examples 1 to 4 and Comparative Examples 1 to 3, 10231) were measured for the bacterial and yeast.

First, samples of various concentrations (0.01 to 10%) prepared by serial dilution of each test substance 10% in 1/2 up to 12 steps 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 for 32 to 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.

For comparison, MIC was measured in the same manner as above after 4-HAP, 1,2-octanediol, and dipropylene glycol were individually treated.

Test substance E. coli P. aeruginosa S. aureus C. albicans 4-HAP 2.0 1.0 1.5 1.5 1,2-octanediol 2.0 2.5 1.5 2.5 Dipropylene glycol <10 <10 <10 <10 Comparative Example 1 1.0 1.0 1.5 1.0 Example 1 1.5 1.0 1.5 1.0 Example 2 &Lt; 1.0 &Lt; 1.0 &Lt; 1.0 &Lt; 1.0 Example 3 &Lt; 1.0 &Lt; 1.0 &Lt; 1.0 &Lt; 1.0 Example 4 &Lt; 1.0 &Lt; 1.0 &Lt; 1.0 &Lt; 1.0 Comparative Example 2 1.5 0.8 1.15 0.8 Comparative Example 3 2.0 1.0 1.5 0.9

As shown in Table 2, Example 1-4 and Comparative Example 1-3 < / RTI > is 4-HAP, 1,2- Octanediol And Dipropylene glycol It was confirmed that it exhibits excellent antimicrobial activity at a significantly lower concentration than in the case of the treatment alone.

In particular, 4- HAP And Of dipropylene glycol Containing a combination Example 1 < / RTI > is 4-HAP or Dipropylene glycol It has a synergistic effect compared to the case of using alone. In addition, 4- HAP , 1,2- Octanediol And Of dipropylene glycol Compositions comprising all combinations ( Example 2- 4) 4- HAP And 1,2- Octanediol Combination( Comparative Example 1), or Dipropylene glycol Alone Compared with those of the other groups.

Furthermore, 4- HAP And 1,2- Octanediol Combination( Comparative Example 1) Crystalline precipitation occurs in the aqueous solution, Dipropylene glycol Additional mixed Example 3-4 does not precipitate crystals in aqueous solution and is convenient for application to cosmetic formulations appear. 4-HAP and Of dipropylene glycol Containing a combination Example 1 It was also found that application to cosmetic formulations was convenient because no precipitation of crystals occurred in aqueous solution.

Test Example 2: Preparation of cosmetic composition and Buoyancy exam

(One) Emulsion Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, an emulsion formulation was prepared as shown in Table 3 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 5 6 4 5 6 Purified water To 100 To 100 To 100 To 100 To 100 Carbomer 940 10 10 10 10 10 Polyacrylate-13 / Polyisobutene / Polysorbate 20 0.8 0.8 0.8 0.8 0.8 Butylene glycol 15 15 15 15 15 Piggy 40 Hydrogenate castor oil 0.8 0.8 0.8 0.8 0.8 Phenyl trimethicone One One One One One L-arginine 0.16 0.16 0.16 0.16 0.16 4-HAP, 1,2-octanediol, DPG (0.3: 0.15: 0.55) One 4-HAP, DPG
(0.5: 0.5) 1.5 4-HAP, 1,2-octanediol (0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant force was measured for Examples 5 and 6 above and compared with Comparative Example 4-6.

First, 50 g of the emulsion formulation was mixed with an initial concentration of 10 ⁶ cfu (colony forming unit, pH 7.0) per each sample in a solution of Escherichia coli (ATCC 8739), Staphylococcus aureus (ATCC 6538), and Pseudomonas aeruginosa (ATCC 99027) colony forming unit / g or more. Then, 1 g of each cosmetic composition was taken at intervals of 0 day, 7 days, 14 days, 21 days and 28 days while culturing in a thermostat of 30 to 32 for 4 weeks, and the number of viable cells was measured.

In addition, the fungus was added at an initial concentration of 10 ⁵ cfu / g or more per each sample, and the mixture was mixed at 25 ° C for 7 days, 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 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 4 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 emulsion Example 5 1 x 10 ⁶ 0 0 0 0 - Example 6 1 x 10 ⁶ <100 <10 0 0 - Comparative Example 4 1 x 10 ⁶ <100 <10 <10 <10 - Comparative Example 5 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 Example 6 1 x 10 ⁶ <100 <10 <100 <100 -

(2) Body wash Formulation Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, body wash formulations were prepared as shown in Table 5 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 7 8 7 8 9 Purified water To 100 To 100 To 100 To 100 To 100 Disodium iodide 0.1 0.1 0.1 0.1 0.1 Polyacrylate-13 / Polyisobutene / Polysorbate 20 8 8 8 8 8 Sodium laureth sulfate 9 9 9 9 9 SAGE 80 Sorbitan Laurate 15 15 15 15 15 Piggy 40 Hydrogenate castor oil 0.8 0.8 0.8 0.8 0.8 Cocoa isopropyl betaine 19 19 19 19 19 Sodium chloride 0.8 0.8 0.8 0.8 0.8 4-HAP, 1,2-octanediol, DPG (0.3: 0.15: 0.55) One 4-HAP, DPG (0.5: 0.5) 1.5 4-HAP, 1,2-octanediol
(0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant force was measured on the above Examples 7 and 8 and compared with Comparative Example 7-9. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion.

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 body
Wash Example 7 1 x 10 ⁶ <10 0 0 0 - Example 8 1 x 10 ⁶ <10 <10 0 0 - Comparative Example 7 1 x 10 ⁶ <10 <10 <10 <10 - Comparative Example 8 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 Example 9 1 x 10 ⁶ <100 <10 <10 <10 -

(3) Non alcohol Of the skin formulations Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, non-alcohol skin formulations were prepared as shown in Table 7 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 9 10 10 11 12 Purified water To 100 To 100 To 100 To 100 To 100 Disodium iodide 0.02 0.02 0.02 0.02 0.02 Butylene glycol 5 5 5 5 5 glycerin 2 2 2 2 2 Tiei 0.1 0.1 0.1 0.1 0.1 Carbomer 940 0.1 0.1 0.1 0.1 0.1 PIGGY-60 Hydrogenated Castor Oil 0.5 0.5 0.5 0.5 0.5 Sodium hyaluronate 0.05 0.05 0.05 0.05 0.05 4-HAP, 1,2-octanediol, dipropylene glycol (0.3: 0.15: 0.55) One 4-HAP, DPG (0.5: 0.5) 1.5 4-HAP, 1,2-octanediol (0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant force was measured on the above Examples 9 and 10 and compared with Comparative Example 10-12. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion.

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 skin Example 9 1 x 10 ⁶ 0 0 0 0 - Example 10 1 x 10 ⁶ <10 <10 0 0 - Comparative Example 10 1 x 10 ⁶ <100 <10 <10 <10 - Comparative Example 11 1 x 10 ⁶ 2.5 x 10 ⁵ 4.0 x 10 ⁵ 1.2 x 10 ⁶ 1.9 x 10 ⁶ +++ Comparative Example 12 1 x 10 ⁶ <100 <10 <10 <10 -

(4) Sun cream Formulation Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, sunscreen formulations were prepared as shown in Table 9 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 11 12 13 14 15 Purified water To 100 To 100 To 100 To 100 To 100 Disodium iodide 0.02 0.02 0.02 0.02 0.02 Butylene glycol 5 5 5 5 5 Yellow iron oxide Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Magnesium sulfate 0.1 0.1 0.1 0.1 0.1 Distearmonium hectorite 0.5 0.5 0.5 0.5 0.5 Aluminum hydroxide 0.5 0.5 0.5 0.5 0.5 Titanium oxide 3 3 3 3 3 Beads wax 2.5 2.5 2.5 2.5 2.5 Piggy 40 Hydrogenate castor oil One One One One One Panyl trimethicone 2 2 2 2 2 Isopropyl palmitate 3 3 3 3 3 Squalane 5 5 5 5 5 Triethoxycaprylyl silane 5 5 5 5 5 4-HAP, 1,2-octanediol, dipropylene glycol (0.3: 0.15: 0.55) One 4-HAP, DPG (0.5: 0.5) 1.5 4-HAP, 1,2-octanediol (0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant force was measured for Examples 11 and 12 and compared with Comparative Examples 13-15. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion.

The results are shown in Table 10 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 Sun cream Example 11 1 x 10 ⁶ 0 0 0 0 - Example 12 1 x 10 ⁶ <10 <10 0 0 - Comparative Example 13 1 x 10 ⁶ <100 <10 0 0 - Comparative Example 14 1 x 10 ⁶ 2.5 x 10 ⁵ 3.5 x 10 ⁵ 9.0 x 10 ⁵ 1.1 x 10 ⁶ +++ Comparative Example 15 1 x 10 ⁶ <100 <10 <10 <10 -

(5) cream formulations Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, cream formulations were prepared as shown in Table 11 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 13 14 16 17 18 Purified water To 100 To 100 To 100 To 100 To 100 Disodium iodide 0.02 0.02 0.02 0.02 0.02 Butylene glycol 5 5 5 5 5 glycerin 5 5 5 5 5 Glyceryl stearate / phage-100 stearate One One One One One Caprylic / capric triglyceride 5 5 5 5 5 Sodium hyaluronate 0.1 0.1 0.1 0.1 0.1 Polyacrylate-13 / Polyisobutene / Polysorbate 20 One One One One One Polysorbate 60 2 2 2 2 2 Squalane 3 3 3 3 3 Panyl trimethicone 0.5 0.5 0.5 0.5 0.5 4-HAP, 1,2-octanediol, dipropylene glycol (0.3: 0.15: 0.55) One 4-HAP, DPG (0.5: 0.5) 1.5 4-HAP, 1,2-octanediol (0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The anti-buoyant force was measured for the above Examples 13 and 14 and compared with Comparative Example 16-18. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion.

The results are shown in Table 12 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 cream Example 13 1 x 10 ⁶ 0 0 0 0 - Example 14 1 x 10 ⁶ <10 0 0 0 - Comparative Example 16 1 x 10 ⁶ <10 <10 0 0 - Comparative Example 17 1 x 10 ⁶ 2.5 x 10 ⁵ 3.0 x 10 ⁵ 4.0 x 10 ⁵ 6.5 x 10 ⁵ +++ Comparative Example 18 1 x 10 ⁶ <100 <10 <10 <10 -

(6) Mask Pack Formulation Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, a mask pack formulation was prepared as shown in Table 13 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 15 16 19 20 21 Purified water To 100 To 100 To 100 To 100 To 100 Disodium iodide 0.02 0.02 0.02 0.02 0.02 Butylene glycol 7 7 7 7 7 glycerin 2 2 2 2 2 kaoline 2 2 2 2 2 Titanium dioxide 5 5 5 5 5 Sodium hyaluronate 0.1 0.1 0.1 0.1 0.1 Polyacrylate-13 / Polyisobutene / Polysorbate 20 One One One One One Polysorbate 60 2 2 2 2 2 Piggy 40 Hydrogenate castor oil One One One One One Panyl trimethicone One One One One One 4-HAP, 1,2-octanediol, dipropylene glycol (0.3: 0.15: 0.55) One 4-HAP, DPG (0.5: 0.5) 1.5 4-HAP, 1,2-octanediol (0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The anti-buoyant force was measured on the above Examples 15 and 16 and compared with Comparative Examples 19-21. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion.

The results are shown in Table 14 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 Mask Pack Example 15 1 x 10 ⁶ 0 0 0 0 - Example 16 1 x 10 ⁶ <100 <10 <10 <10 - Comparative Example 19 1 x 10 ⁶ <1000 <100 <100 <100 - Comparative Example 20 1 x 10 ⁶ 2.5 x 10 ⁵ 3.0 x 10 ⁵ 4.0 x 10 ⁵ 6.5 x 10 ⁵ +++ Comparative Example 21 1 x 10 ⁶ <100 <10 <10 <10 -

(7) Formulations of Foundation Formulations Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, a foundation formulation was prepared as shown in Table 15 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 17 18 22 23 24 Purified water To 100 To 100 To 100 To 100 To 100 Disodium iodide 0.02 0.02 0.02 0.02 0.02 Butylene glycol 5 5 5 5 5 Yellow iron oxide Suitable amount Suitable amount Suitable amount Suitable amount Suitable amount Magnesium sulfate 0.1 0.1 0.1 0.1 0.1 Distearmonium hectorite 0.5 0.5 0.5 0.5 0.5 Aluminum hydroxide 0.5 0.5 0.5 0.5 0.5 Titanium oxide 3 3 3 3 3 Beads wax 3 3 3 3 3 Piggy 40 Hydrogenate castor oil One One One One One Panyl trimethicone One One One One One Isopropyl palmitate 5 5 5 5 5 Triethoxycaprylyl silane 5 5 5 5 5 4-HAP, 1,2-octanediol, dipropylene glycol (0.3: 0.15: 0.55) One 4-HAP, DPG (0.5: 0.5) 1.5 4-HAP, 1,2-octanediol (0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant force was measured on the above Examples 17 and 18 and compared with Comparative Examples 22-24. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion.

The results are shown in Table 16 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 foundation Example 17 1 x 10 ⁶ 0 0 0 0 - Example 18 1 x 10 ⁶ <10 0 0 0 - Comparative Example 22 1 x 10 ⁶ <10 <10 0 0 - Comparative Example 23 1 x 10 ⁶ 1.5 x 10 ⁵ 2.0 x 10 ⁵ 3.0 x 10 ⁵ 5.0 x 10 ⁵ +++ Comparative Example 24 1 x 10 ⁶ <100 <10 <10 <10 -

(8) Shampoo formulations Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, a shampoo formulation was prepared as shown in Table 17 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 19 20 25 26 27 Purified water 54.1 54.1 53.9 54.1 53.9 Acrylate / Stearth-20 methacrylate crosspolymer 3.5 3.5 3.5 3.5 3.5 Decyl glucoside E 2.0 2.0 2.0 2.0 2.0 Glyceryl oleate 2.5 2.5 2.5 2.5 2.5 Sodium lauryl sulfate 10.0 10.0 10.0 10.0 10.0 Sodium laureth sulfate 10.0 10.0 10.0 10.0 10.0 Triethanolamine 1.2 1.2 1.2 1.2 1.2 Di-sodium laureth sulfosuccinate 7.0 7.0 7.0 7.0 7.0 Cocoamidopropyl betaine 3.8 3.8 3.8 3.8 3.8 Disodium ethylenediamine tetraacetic acid 0.3 0.3 0.3 0.3 0.3 1,3-propanediol 5.0 5.0 5.0 5.0 5.0 4-HAP, 1,2-octanediol, dipropylene glycol (0.3: 0.15: 0.55) One 4-HAP, DPG (0.5: 0.5) 1.5 4-HAP, 1,2-octanediol (0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant force was measured on the above Examples 19 and 20 and compared with Comparative Examples 25-27. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion.

The results are shown in Table 18 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 shampoo Example 19 1 x 10 ⁶ <10 0 0 0 - Example 20 1 x 10 ⁶ <10 <10 0 0 - Comparative Example 25 1 x 10 ⁶ <10 <10 <10 0 - Comparative Example 26 1 x 10 ⁶ 3.5 x 10 ⁵ 4.0 x 10 ⁵ 5.0 x 10 ⁵ 5.5 x 10 ⁵ +++ Comparative Example 27 1 x 10 ⁶ <100 <10 <10 <10 -

(9) Wet tissue formulation Buoyancy exam

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, a wet tissue formulation was prepared as shown in Table 5 below. As an additional comparative example, no chemical preservative was used, or an emulsion formulation was prepared using a combination of paraben and phenoxyethanol as a chemical preservative.

Ingredients (Unit: wt%) Example Comparative Example 21 22 28 29 30 Purified water To 100 To 100 To 100 To 100 To 100 Acrylate / Stearth-20 methacrylate crosspolymer 0.60 0.60 0.60 0.60 0.60 Mineral oil 4.5 4.5 4.5 4.5 4.5 Isopropyl palmitate 4.5 4.5 4.5 4.5 4.5 Propylene glycol 1.0 1.0 1.0 1.0 1.0 Dipropylene glycol 0.8 0.8 0.8 0.8 0.8 Piggy 40 Hydrogenate castor oil 1.0 1.0 1.0 1.0 1.0 4-HAP, 1,2-octanediol, dipropylene glycol (0.3: 0.15: 0.55) One 4-HAP, DPG (0.5: 0.5) 1.5 4-HAP, 1,2-octanediol (0.5: 0.5) One Ethyl paraben 0.05 Phenoxyethanol 0.9

The buoyant forces were measured on the above Examples 21 and 22 and compared with Comparative Examples 28-30. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion.

The results are shown in Table 20 below.

Cosmetics Number of bacteria (cfu / g) mold 0 day Day 7 Day 14 Day 21 Day 28 wet tissue Example 21 1 x 10 ⁶ <10 0 0 0 - Example 22 1 x 10 ⁶ <10 <10 <10 0 - Comparative Example 28 1 x 10 ⁶ <100 <100 <10 <10 - Comparative Example 29 1 x 10 ⁶ 3.1 x 10 ⁵ 8.0 x 10 ⁵ 1.2 x 10 ⁶ 3.2 x 10 ⁶ +++ Comparative Example 30 1 x 10 ⁶ <1000 <100 <10 <10 -

remind Buoyancy According to the results of the test, 4- HAP And 1,2- Octanediol In combination Additional to Dipropylene glycol Included Example Cosmetics 4- HAP And 1,2- Octanediol Compared to the case where only the combination is included, Buoyancy in the room It was confirmed to be remarkably excellent. In addition, 4- HAP And Of dipropylene glycol Containing a combination Example Cosmetics 4- HAP And 1,2- Octanediol Containing a combination To cosmetics Lt; RTI ID = 0.0 > Buoyancy in the room Remarkably superior . As well as In all of the above embodiments, Cosmetics Preservative Ethyl paraben And phenoxyethanol were used as the antioxidants.

Test Example 3: 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 21 below (Unit: wt%).

The patches were attached to the upper part of the subject's back and 20 [mu] l of 25% preservative was applied using IQ chamber chemistry (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 skin irritation of each preservative, 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 21 below.

[Equation 1]

Test substance Furtherance Primary skin irritation index ^*
(P.C.I) Example 23 Containing 0.6% 4-HAP, 0.3% 1,2-octanediol and 1.1% dipropylene glycol in butylene glycol 0.04 Example 24 1.0% 4-HAP in butylene glycol, 1.0% 1,2-octanediol 0.04 Comparative Example 31 1.0% 4-HAP and 1.0% 1,2-octanediol in butylene glycol 0.14 Comparative Example 32 0.1% methyl paraben, 1% phenoxyethanol in butylene glycol 0.14 Comparative Example 33 10% 1,2-pentanediol in butylene glycol 0.38 Comparative Example 34 10% Butylene glycol aqueous solution (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 21, Example 23 involving the combination of 4-HAP and 1,2-octanediol, including the combination of 4-HAP, 1,2-octanediol, and dipropylene glycol, Compared with Comparative Example 31, which contained a combination of HAP and 1,2-octanediol, and Comparative Example 32 or 33, which contained 1,2-pentanediol, or methylparaben and phenoxyethanol, which are mainly used in existing cosmetic products, Index was 9 times or more lower than that of Comparative Example. Thus, it was confirmed that the composition for external application for skin according to one embodiment of the present invention can be safely applied to skin.

Test Example 4: Sensory test

20 panelists were rubbed with 1.5 ml of each of the wet tissue formulations of Example 15-16 and Comparative Examples 19 and 21 at random on the side of the face nose and on the left and right sides of the ball to rub on the skin, Stimulation " was evaluated according to the evaluation criteria shown in Table 22 below, and the results are shown in Table 22. < tb > < TABLE >

score 0-0.39 0.4-1.0 1.1-2.0 2.1-3.0 Irritability none Minimal usually Severe

Example 15 Example 16 Comparative Example 19 Comparative Example 21 Stinginess 0.1 0.1 0.7 0.56 Burning 0.15 0.2 0.8 1.50 Average 0.13 0.15 0.75 1.03

As shown in Table 23, the formulations of Examples 15 and 16 according to one embodiment of the present invention exhibited a stimulation feeling of at least five times lower than that of the formulations of Comparative Examples 19 and 21, It can be safely applied to the skin without inducing it.

According to the above results, the cosmetic preserving agent according to one embodiment of the present invention is excellent not only in buoyancy and antibacterial activity but also in usability and does not cause toxicity, skin irritation, irritation and allergy due to use of a chemical preservative, Of the present invention.

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

An acetophenone derivative represented by the following general formula (1), or a cosmetically or pharmacologically acceptable salt thereof
(I)

(Wherein R ₁ represents hydrogen or methyl, and R ₂ represents hydrogen or hydroxy); And
Preservatives for external preparations for skin containing dipropylene glycol.

The process according to claim 1, wherein the 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, Wherein the composition further comprises an alkane diol selected from the group consisting of 1,6-hexanediol, 1,8-octanediol, and any combination thereof. .

The method according to claim 1, wherein the acetophenone derivative

&Lt; / RTI > and any combination thereof.

3. The composition according to claim 2, wherein the alkane diol is selected from the group consisting of 1,2-octanediol, 1,2-hexanediol, 1,2-decanediol, and any combination thereof. .

The method of claim 2, wherein the acetophenone derivative

&Lt; / RTI > and any combination thereof,
Wherein said alkane diol is selected from the group consisting of 1,2-octanediol, 1,2-hexanediol, 1,2-decanediol, and any combination thereof.

3. The method of claim 2,
4-hydroxyacetophenone;
1,2-octanediol; And
A preservative for external preparation for skin comprising dipropylene glycol.

The preservative for external use for skin according to claim 6, which comprises 4-hydroxyacetophenone, 1,2-octanediol, and dipropylene glycol in a weight ratio of 0.01 to 10: 0.01 to 10: 0.01 to 10.

8. The composition according to claim 7, which comprises 4-hydroxyacetophenone, 1,2-octanediol, and dipropylene glycol in a weight ratio of 0.3: 0.15: 0.55.

9. A cosmetic composition comprising the preservative for external preparation for skin according to any one of claims 1 to 8.

The cosmetic composition 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 cosmetic composition.

The cosmetic composition according to claim 9, 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 styling gel, a lubricant, a toothpaste, and a wet tissue.

9. A pharmaceutical composition for external application for skin comprising the preservative for external preparation for skin according to any one of claims 1 to 8.

13. The pharmaceutical composition according to claim 12, 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.

The pharmaceutical composition according to claim 12, 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 to human skin.

15. The pharmaceutical composition according to claim 14, wherein the pharmaceutical composition is for systemic or local action.

A method for producing an external preparation for skin, which comprises using a preservative for external preparations for skin according to any one of claims 1 to 8 as a preservative.

The manufacturing method according to claim 16, wherein the external preparation for skin is a cosmetic composition or a pharmaceutical composition for external application to skin.

18. The method according to claim 17, 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.