KR20190069836A - A preservative for skin external application, and a cosmetic composition and a pharmaceutical composition comprising the same - Google Patents

Abstract

A preservative for skin external application according to the present invention has excellent antibacterial, antifungal and antiseptic properties without using conventional chemical preservatives, and rarely causes side effects on the skin. In addition, the preservative for skin external application does not precipitate crystals even when used in an aqueous formulation, is excellent in processability and preservation, and thus can be widely used in cosmetics, external skin medicines, external skin care products and the like.

Description

[0001] The present invention relates to a preservative for external preparation for skin, a cosmetic composition containing the same, 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 three-component 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 preserving agent which is more effective and safe, and is not limited in application to a solubilization formulation.

Korean Patent Publication No. 10-2013-0049729 (May 14, 2013) Korean Patent Publication No. 10-2013-0074983 (Jul. 05, 2013)

Disclosure of the Invention The present invention has been conceived to solve the above-mentioned problems. It is an object of the present invention to provide an antimicrobial and antifungal agent by incorporating diol 1,3-butylene glycol, dipropylene glycol or a mixture thereof into caprylic hydroxamic acid It is another object of the present invention to provide a preservative for external preparation for skin which does not precipitate crystals when used in an aqueous preparation and does not cause side effects such as allergy to the skin, and a cosmetic composition and pharmaceutical composition containing the same.

The present invention relates to a preservative for external preparation for skin, a cosmetic composition containing the same, and a pharmaceutical composition.

One aspect of the present invention relates to a preservative for external preparation for skin comprising dipropylene glycol in caprylhydroxamic acid represented by the following formula (1).

[Chemical Formula 1]

In the present invention, the preservative is selected from the group consisting of 1,2-hexanediol, 1,2-pentanediol, 1,2-octanediol, One or more alkanediols selected from 1,2-decanediol, 1,6-hexanediol and 1,8-octanediol may be used. And more specifically, may be any one or a plurality selected from 1,2-octanediol, 1,2-hexanediol, and 1,2-pentanediol.

More specifically, the preservative may comprise caprylhydroxamic acid, 1,2-hexanediol and dipropylene glycol wherein the preservative is caprylic hydroxamic acid 1 to 50 parts by weight per 100 parts by weight of dipropylene glycol, And 10 to 150 parts by weight of 1,2-hexanediol.

Another aspect of the present invention relates to a cosmetic composition comprising the preservative for external preparation for skin, wherein the cosmetic composition comprises 0.01 to 20% by weight of a preservative for external preparation for skin among 100% by weight of the whole, It is made up of sunscreen, foundation, essence, gel, pack, mask pack, foam cleanser, body cleanser, softener liner, eyeliner, shampoo, rinse, soap, regular agent, hairdressing cream, hair styling gel, lubricant, toothpaste and wipes May have any one of the formulations selected from the group.

Another aspect of the present invention relates to a pharmaceutical composition for external application for skin comprising a preservative for external preparations for skin, wherein the pharmaceutical composition comprises 0.01 to 20% by weight of a preservative for external preparation for skin out of 100% , A liniment, an ointment, a pasta, a cataplasma, a suspension, an oil, a lotion, an aerosol, and a suppository.

The preservative for external preparations for skin according to the present invention is excellent in antimicrobial, antifungal and antibacterial properties without using a conventional chemical preservative and hardly causes side effects to the skin. Further, even when used in a water-based preparation, crystals are not precipitated, and the processability and storage stability are excellent, which can be widely used in cosmetics, drugs for external use on the skin, and household products for external use on the skin.

Hereinafter, the preservative for external preparation for skin according to the present invention will be described in more detail with reference to specific examples. The following specific embodiments are provided by way of example so that those skilled in the art can fully understand the spirit of the present invention.

Therefore, the present invention is not limited to the embodiments shown below, but may be embodied in other forms. The embodiments shown below are only for clarifying the spirit of the present invention, and the present invention is not limited thereto.

Here, unless otherwise defined, technical terms and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. In the following description, the gist of the present invention is unnecessarily blurred And a description of the known function and configuration will be omitted.

Also, the singular forms as used in the specification and the appended claims are intended to include the plural forms as well, unless the context clearly indicates otherwise.

In describing the components of the present invention, terms such as first, second, A, B, (a), and (b) may be used. These terms are intended to distinguish the constituent elements from other constituent elements, and the terms do not limit the nature, order or order of the constituent elements. When a component is described as being "connected", "coupled", or "connected" to another component, the component may be directly connected to or connected to the other component, It should be understood that an element may be "connected," "coupled," or "connected."

The term " external preparation for skin " in the present invention is a concept covering the entire composition applied to the skin. For example, various cosmetics such as basic cosmetics, makeup cosmetics, and hair cosmetics; A pharmaceutical composition such as an ointment preparation, a cream preparation, a lotion preparation and the like, and a pharmaceutical composition applied to the skin for external use including quasi-drugs.

The term " antimicrobial " in the present invention means resistance to all contaminating microorganisms such as bacteria, fungi and yeast. "Antimicrobial activity" means a defense against these contaminating microorganisms. Which is a concept that includes antimicrobial activity.

In the present invention, the term 'preservative agent' refers to a substance which has a buoyant or antioxidant ability to prevent deterioration of a product for a long time and maintain its original state. The term 'preservative power' It means defense ability.

The inventors of the present invention have made intensive studies on a composition that can be used as a preservative in an external skin product without adding a chemical preservative such as parabens, and have found that when caprylic hydroxamic acid and diol such as 1,3-butanediol or dipropylene glycol Was found to have synergistic antimicrobial activity and preservation ability and at the same time to have excellent flotation power and skin irritation remarkably lower than conventional parabens preservatives. In addition, the combination of caprylic hydroxamic acid and alkane diol conventionally has found that crystals precipitate in a solubilized formulation in which water is the main solvent, whereas crystals are not precipitated in the composition according to the present invention, thereby completing the present invention.

The present invention can include diol 1,3-butylene glycol, dipropylene glycol or mixtures thereof in caprylhydroxamic acid.

In the present invention, the caprylic hydroxamic acid is a substance having a structure represented by Chemical Formula 1 below, which is based on palm oil, and is generally used to block metal ions.

[Chemical Formula 1]

The caprylic hydroxamic acid is a soft, excellent preservative effective at neutral pH and exhibits an excellent preservative effect when compounded in a cosmetic composition or the like. It can be used as a preservative without the addition of a chemical preservative such as parabens such as paraoxybenzoic ester . In addition, even if it is absorbed into the body, it rapidly moves into the blood and is mostly discharged into urine, and some is metabolized by amide or acid and is not toxic.

The caprylic hydroxamic acid is preferably contained in an amount of 1 to 50 parts by weight, more preferably 5 to 15 parts by weight, based on 100 parts by weight of dipropylene glycol based on dipropylene glycol in a preservative. When the caprylic hydroxamic acid is added in an amount less than the above range, antimicrobial activity and preservation ability may be deteriorated, and if it exceeds the above range, stability of the formulation may be deteriorated.

The diol acts to confer an antimicrobial activity on the composition and is mixed with the caprylic hydroxamic acid to remove bacteria, fungi and algae to prevent the cosmetic or medical composition from being contaminated, and the caprylic hydroxamic acid When used alone or in combination with other diols, the antimicrobial effect against bacteria and fungi is enhanced.

When the diol is mixed with the caprylic hydroxamic acid, crystals should not be precipitated. In particular, crystallization should not occur in a solubilized formulation containing water as a solvent. Examples of such diols include 1,3-butylene glycol and dipropylene glycol, which may be used alone or in combination.

In the present invention, the amount of the diol to be added is not limited, but is preferably 1% by weight or more, more preferably 0.01 to 0.99% by weight based on 100% by weight of the total composition. When the diol is added in an amount of less than 0.01% by weight, the antimicrobial activity against bacteria and fungi is lowered. When the diol is added in an amount of more than 0.99% by weight, stability of the formulation may be deteriorated.

The preservative according to the present invention may also be selected from the group consisting of 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, 1 , 1,6-hexanediol, and 1,8-octanediol. The term " alkane diol "

Similar to the diol, the alkanediol has an antibacterial activity against bacteria and fungi when mixed with the caprylic hydroxamic acid, and is uniformly mixed without causing precipitation of crystals in the aqueous solution. Thus, water such as cosmetics is dissolved in a main solvent As a solubilization formulation.

The alkane diol to be added in the present invention is preferably 10 to 150 parts by weight, more preferably 50 to 120 parts by weight, based on 100 parts by weight of dipropylene glycol based on dipropylene glycol in the preservative. When the alkanediol is added in an amount less than the above range, the antibacterial activity may be lowered, and if it is added in an amount exceeding the above range, the stability of the formulation may be deteriorated.

The combination ratio of the preservative for external preparation for skin may vary depending on the specific compound of each component, and may include any ratio showing an effective antibacterial activity.

When caprylic hydroxamic acid and dipropylene glycol are mixed, they may be contained in a weight ratio of 0.01 to 10: 0.01 to 10, and more specifically 0.01 to 0.5: 0.1 to 5.0. In one embodiment, the preservative for dermatologic preparations may comprise caprylhydroxamic acid and dipropylene glycol in a weight ratio of about 0.15: 2.95.

0.01 to 10: 0.01 to 10: 0.01 to 10, and more specifically 0.1 to 0.5: 0.1 to 3.0: 0.1, respectively, when the caprylic hydroxamic acid, the alkanediol and the dipropylene glycol are mixed, To 5 parts by weight. In one embodiment, the preservative for skin topical agents may comprise caprylhydroxamic acid: alkanediol: dipropylene glycol in a weight ratio of about 0.15: 0.9: 1.95.

In one embodiment, the preservative for external preparation for skin may comprise caprylhydroxamic acid, 1,2-hexanediol and dipropylene glycol in a weight ratio of about 0.01 to 10: 0.01 to 10: 0.01 to 10, Specifically, it may be in a weight ratio of 0.1 to 0.5: 0.1 to 3.0: 0.1 to 5.0. In one embodiment, the caprylic hydroxamic acid, 1,2-hexanediol, and dipropylene glycol can be included in a weight ratio of about 0.15: 0.9: 1.95.

In addition, the present invention can provide a cosmetic composition comprising 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 lotion 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. The present invention relates to a cosmetic composition comprising a carrier, a solvent, a surfactant, an emulsifier, a tackifier, a conditioner, a softener, a skin protecting ingredient, a moisturizer, a thickener, a lubricant, a filler, ≪ / RTI >

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, and the like. But is not limited thereto.

Examples of the surfactant include alkyl sulfates (e.g., sodium lauryl sulfate, ammonium lauryl sulfate, sodium cetearyl sulfate); Alkyl sulphoacetates such as sodium lauryl sulphoacetate; Alkyl ether sulfates such as sodium laureth sulfate, sodium trideceth sulfate, sodium oleate sulfate, ammonium laureth sulfate; Alkyl ether sulfosuccinates such as disodium laureth sulfosuccinate; Alkyl glycosides (e.g., decyl glucoside, lauryl glucoside); Alkyl isethionate amphoteric compounds such as cocamidopropyl betaine, sodium cocoamphoacetate, sodium lauroamphoacetate, disodium lauroamphodiacetate, disodium cocoamphodiacetate, sodium lauroamphosphorate, Potassium or ammonium salts of amphoteric compounds mentioned above, capryl / capramidopropyl betaine, undecylenamidopropyl betaine, laurocomidopropyl betaine) and fatty alcohol poly Glycol ethers and the like.

Such emulsifiers include salts of fatty acids such as sodium stearate or sodium palmitate, organic soaps such as mono-, di- or triethanolaminoleate, sulfated or sulfonated compounds such as sodium lauryl sulfate or sodium cetyl Cationic compounds such as quaternary ammonium salts; non-ionic compounds such as fatty alcohols, fatty acid esters with saturated or unsaturated fatty acids, polyoxyethylene esters of fatty acids, Or polyoxyethylene ethers, polymers from ethylene oxide and propylene oxide or propylene glycol, amphoteric compounds such as phosphatides, proteins such as gelatin, casein, alkylamidobetaines, alkylbetaines and ampholytes Alkylate, alkylpolyoxyethylene phosphate or the corresponding acid, a silicone derivative such as alkyldimethicone, Rheology) and the like.

The above-mentioned starches may be fatty alcohols or fatty acid esters and mixtures thereof such as acetylated lanolin alcohol, aluminum stearate, carbomer, cetyl alcohol, glyceryl oleate, glyceryl stearate, glyceryl stearate, PEG 100 stearate, magnesium stearate, magnesium sulfate, oleic acid, stearic acid, stearyl alcohol, myristyl myristate, isopropyl palmitate, wax and its synthetic equivalents and carbomers.

Examples of the conditioner include alkylamidoammonium lactate, settimoronium chloride and distearoylhydroxyethylmonium methosulfate and cetearyl alcohol, cetyl dimethicone, cetyl ricinoleate, dimethicone, laureth-23, Lauryl-4, polydecene, retinyl palmitate, quaternized protein hydrolysates, quaternized cellulose and starch derivatives, quaternized copolymers of acrylic acid or methacrylic acid or salts, and quaternized silicone derivatives.

Examples of the softening agent include cetearyl isononanoate, cetearyl octanoate, decyl oleate, isooctyl stearate, coco caprylate / caprate, ethylhexyl hydroxystearate, ethylhexyl isononanoate, PEG-7 glyceryl cocoate, petrolatum, ozokerite cyclomethicone, dimethicone, isopropyl myristate, isopropyl myristate, oleyl oleate, hexyl laurate, , Dimethicone copolyol, dicaprylyl ether, butyrospermum parc, bucksukinensis, canola, carnauba vera, copernicia serifera, oenotera biannis, ellais gentinis, Lanolin, hydrogenated castor oil, hydrogenated polyisobutene, sucrose cocoate, stearoxyacetate, lauric acid, Dimethicone, lanolin alcohol, isohexadecane, and the like.

Examples of the skin protecting ingredient include plant extracts, bisabolol, antiinflammatory agents, urea, allantoin, panthenol and panthenol derivatives, phytanetriol, vitamins A, E, C and D, ceramide and lecithin derived from animals or plants .

Examples of the moisturizing agent include butylene glycol, cetyl alcohol, dimethicone, dimyristyl tartrate, glucose glycerides-26, glycerin, glyceryl stearate, hydrolyzed milk protein, lactic acid, lactose and other sugars, Lecithin, octoxyglycerin, PEG-12, PEG-135, PEG-150, PEG-20, PEG-8, pentylene glycol, hexylene glycol, Propylene glycol, sodium hyaluronate, sodium lactate, sodium PCA, sorbitol, succinoglycan, synthetic wax, tri-C14-15 alkyl citrate, and starch.

Examples of the thickener include acrylate / stearate-20 methacrylate copolymer, carbomer, carboxymethyl starch, cera alba, dimethicone / vinyl dimethicone crosspolymer, propylene glycol alginate, hydroxyethyl cellulose, Cellulose, silica, silica dimethylsilylate, xanthan gum, hydrogenated butylene / ethylene / styrene copolymer, and the like.

Examples of the lubricant include adipic acid, fumaric acid and its salt, benzoic acid and its salts, glycerin triacetate, sodium or magnesium lauryl sulfate, magnesium stearate, solid polyethylene glycol, polyvinylpyrrolidone, boric acid, Mono-palmitate, myristyl alcohol, cetyl alcohol, cetyl stearyl alcohol, talc, calcium or magnesium salts of higher fatty acids, mono-, di- or triglycerides of higher fatty acids, and polytetrafluoroethylene.

Examples of the antioxidant include sulfite (e.g., sodium sulfite), tocopherol or a derivative thereof, ascorbic acid or a derivative thereof, citric acid, propyl gallate, chitosan glycolate, cysteine, N-acetylcysteine + zinc sulfate, thiosulfate Sodium thiosulfate) and polyphenols.

The composition may also contain various active ingredients depending on the application site of the skin. Examples of such active ingredients include antimicrobial agents, antiinflammatory agents, plant extracting agents, bisabolol, panthenol, tocopherol, antioxidants, anti-irritants or antidandruff agents, antioxidants such as retinol and melibiose ≪ / RTI > Other suitable active agents include, for example, Medicago officinalis, Actinidia chinensis, allantoin, Aloe barbadensis, Anona cherimolia, Anthemis nobilis, Arachis hypogaea, Arnica Montana, Avena sativa, Beta-carotene, Bisabolol, Borago < (R) > Calendula officinalis, Camellia sinensis, Camphor, Candida bombicola, Capryloylglycine, Carica papaya, Camellia officinalis, Butyleneglycol, Calendula officinalis, Camellia sinensis, But are not limited to, Centaurea cyanus, cetylpyridinium chloride, Chamomilla recutita, Chenopodium quinoa, Chinchona succirubra, Chondrus crispus, Citrus aurantium dulcis, Citrus grandis, Citrus limonum, Cocos nucifera, Coffea Arabica, ), Crataegus monogina, Cucumis melo, Dichlorophenylimidazole dioxolane, Enteromorpha compressa, Equsetum arvense, Ethoxydiglycol, Fructaria chiloensis, Gentiana lutea, Ginkgo biloba, glycerin, glyceryl laurate, Glycyrrhiza glabra (Glycyrrhiza) glabra, Hamamelis virginiana, heliotropin, hydrogenated palmaglyceride, citrate, hydrolyzed castor oil, hydrolyzed wheat protein, Hypericum perf oratum, Iris florentina, Juniperus communis, Lactis proteinum, Lactose, Lawsonia inermis, Linerul, But are not limited to, Linum usitatissimum, lysine, magnesium aspartate, Magnifera indica, Malva sylvestris, mannitol, mel melaleuca alternifolia, Mentha piperita, menthol, methyl lactate, Mimosa tenuiflora, Nymphaea alba, Oleflaur, Oryza sativa, panthenol, para-pumuri riquimud, PEG PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-8 caprylic / capric acid, Persia gracilisma ( Persea gratissima), petrolatum, potassium aspartate, potassium But are not limited to, beet, propyleneglycol, Prunus amygdalus dulcis, Prunus armeniaca, Prunus persica, retinyl palmitate, Ricinus communis, Rosa canina, Rosmarinus officinalis, Rubus idaeus, Salicylic acid, Sambucus nigra, Sarcosine, Serenoa serrulata ), Simmondsia chinensis, sodium carboxymethyl betaglucan, sodium cocoylamino acid, sodium hyaluronate, sodium palmitoyl praline, stearoxytrimethylsilane, stearyl alcohol, sulfated TEA-ricinoleate, talc , Thymus vulgaris, Tilia cordata, tocopherol, tocopheryl acetate, tridecset-9, triticum vulgare, tyrosine, undecyl One glycine, urea, Park Sihoo titanium MIR butyl Ruth (Vaccinium myrtillus), valine, there may be mentioned zinc oxide, zinc sulfate and the like.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. However, the following examples and comparative examples are only illustrative of the present invention in detail, and the present invention is not limited by the following examples.

The physical properties of the specimens prepared through the following examples and comparative examples were measured as follows.

(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. The antimicrobial activity was tested using the preservative prepared next. Specifically, the antibacterial activity against bacteria and yeasts such as Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538) and Candida albicans (ATCC 10231) To 10 ml of a liquid culture prepared by adding various concentrations (0.01 to 10%) of samples prepared by serial dilution of 10% of each sample to 1/2 in 12 steps, and adding them to a tryptic soy medium (TSB) Bacteria and yeast were each inoculated at a concentration of 106 / 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. For comparison, MICs were measured in the same manner as above after caprylic hydroxamic acid, 1,2-hexanediol, and dipropylene glycol were individually treated.

[Table 1]

(CHA: caprylhydroxamic acid, DPG: dipropylene glycol, HD: 1,2-hexanediol)

[Table 2]

As shown in Table 2, the preservatives of Examples 1 to 4 and Comparative Examples 1 to 3 were significantly lower in concentration than caprylhydroxamic acid, 1,2-hexanediol and dipropylene glycol alone And exhibit excellent antimicrobial activity.

In particular, the composition of Example 1 comprising a combination of caprylic hydroxamic acid and dipropylene glycol was shown to have a significant synergistic effect compared to the case of using them alone. In Comparative Example 1 in which caprylic hydroxamic acid and 1,2-hexanediol were combined, crystal precipitation occurred in an aqueous solution, whereas in Examples 3 and 4 in which dipropylene glycol was further mixed, crystal precipitation did not occur in an aqueous solution, It seems to be applicable to formulation. Example 1, which combines caprylhydroxamic acid and dipropylene glycol, also appears to be applicable to cosmetic formulations since crystallization does not occur in an aqueous solution.

(Test Example 2) - Determination of crystallization of the cosmetic composition and flotation test

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 other chemical preservative was used (Comparative Example 5) or an emulsion (Comparative Example 6) using a combination of paraben and phenoxyethanol as a chemical preservative was added.

The microbial cells (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), and Staphylococcus aureus (ATCC 6538) were inoculated in 50 g of the emulsion formulation shown in Table 3 below in an initial concentration of 10 ⁶ cfu , Colony forming unit) / g or more. Next, 1 g of each cosmetic composition was taken at 0, 7, 14, 21 and 28 days intervals while culturing in a thermostat at 30 to 32 캜 for 4 weeks, and the number of viable cells was measured. 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 of the yeast, the presence or absence of swelling, the hypha of the surface of the sample, and the occurrence of spores were measured. The results were shown in Table 4 below.

-: 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

[Table 3]

[Table 4]

(Test Example 3) - Repellency test of cosmetic composition

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, a body wash formulation was prepared as shown in Table 5 below. As an additional comparative example, no other chemical preservative was used (Comparative Example 8) or an emulsion (Comparative Example 9) using a combination of paraben and phenoxyethanol as a chemical preservative was added.

Also, the buoyant force was measured on the composition. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion, and the results are shown in Table 6 below.

[Table 5]

[Table 6]

(Test Example 4) - Anti-buoyancy test of non-alcoholic skin formulations

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, nonalcoholic skin formulations were prepared as shown in Table 7 below. As an additional comparative example, no other chemical preservative was used (Comparative Example 11) or an emulsion (Comparative Example 12) using a combination of paraben and phenoxyethanol as a chemical preservative was added. Also, the buoyant force was measured on the composition. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion, and the results are shown in Table 8 below.

[Table 7]

[Table 8]

(Test Example 5) - Flotation test of sunscreen formulation

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 other chemical preservative was used (Comparative Example 14), or an emulsion using a combination of paraben and phenoxyethanol as a chemical preservative (Comparative Example 15) was added. Also, the buoyant force was measured on the composition. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion, and the results are shown in Table 10 below.

[Table 9]

[Table 10]

(Test Example 6) - Flotation test of cream formulations

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 other chemical preservative was used (Comparative Example 17) or an emulsion (Comparative Example 18) using a combination of paraben and phenoxyethanol as a chemical preservative was added. Also, the buoyant force was measured on the composition. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion, and the results are shown in Table 12 below.

[Table 11]

[Table 12]

(Test Example 7) - Buffering test of the mask pack formulation

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, cream formulations were prepared as shown in Table 13 below. As an additional comparative example, no other chemical preservative was used (Comparative Example 20), or an emulsion using a combination of paraben and phenoxyethanol as a chemical preservative (Comparative Example 21) was added. Also, the buoyant force was measured on the composition. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion, and the results are shown in Table 14 below.

[Table 13]

[Table 14]

(Test Example 8) - Flotation test of foundation formulation

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, cream formulations were prepared as shown in Table 15 below. As an additional comparative example, no other chemical preservative was used (Comparative Example 23) or an emulsion (Comparative Example 24) using a combination of paraben and phenoxyethanol as a chemical preservative was added. Also, the buoyant force was measured on the composition. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion, and the results are shown in Table 16 below.

[Table 15]

[Table 16]

(Test Example 9) - Flotation test of shampoo formulation

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, cream formulations were prepared as shown in Table 17 below. As an additional comparative example, no other chemical preservative was used (Comparative Example 23) or an emulsion (Comparative Example 24) using a combination of paraben and phenoxyethanol as a chemical preservative was added. Also, the buoyant force was measured on the composition. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion, and the results are shown in Table 18 below.

[Table 17]

[Table 18]

(Test Example 10) - Flotation test of a wet tissue formulation

Using the preservatives of Examples 1 and 4 and the preservative of Comparative Example 1, cream formulations were prepared as shown in Table 19 below. As an additional comparative example, no other chemical preservative was used (Comparative Example 29) or an emulsion using a combination of paraben and phenoxyethanol as a chemical preservative (Comparative Example 30) was added. Also, the buoyant force was measured on the composition. The evaluation of the buoyant force was carried out in the same manner as the buoyancy test of the emulsion, and the results are shown in Table 20 below.

[Table 19]

[Table 20]

In addition to the combination of caprylic hydroxamic acid and 1,2-hexanediol, as in the results of the buoyancy test, the cosmetic composition of the Examples comprising dipropylene glycol alone showed a combination of caprylic hydroxamic acid and 1,2-hexanediol It can be seen that the anti-buoyancy is remarkably excellent in all the above-mentioned formulations. The cosmetic compositions of the examples comprising a combination of caprylic hydroxamic acid and dipropylene glycol were found to be superior to the cosmetic compositions comprising a combination of caprylhydroxamic acid and 1,2-hexanediol in all formulations And it was confirmed that in all of the examples, the repelling force was remarkably superior to that in the case of using ethylparaben and phenoxyethanol as cosmetic preservatives conventionally used conventionally.

(Test Example 11) - Preparation of preservative and skin irritation test

To confirm skin irritation, a preservative for skin external preparation was prepared according to the composition shown in Table 21 (unit: wt%). The patch was attached to the upper part of the subject's back and 20 25 of 25% preservative was applied using IQ Chamberkem Technique (Sweden). The first reading was tested 30 minutes after removing the patch, and the second reading was performed after 24 hours. To determine the intensity of 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 evaluate the skin irritation And the results are shown in Table 21 below.

[Equation 1]

[Table 21]

Example 24, which includes the combination of caprylic hydroxamic acid and dipropylene glycol with Example 23, including combinations of caprylhydroxamic acid, 1,2-hexanediol, and dipropylene glycol, as shown in Table 21, Compared with Comparative Example 31, which contained a combination of ricosamic acid and 1,2-hexanediol, and Comparative Example 32 or 33, which contained 1,2-pentanediol or methylparaben and phenoxyethanol, which are mainly used in existing cosmetics, The index was found to be at least 9 times lower.

(Test Example 12) - Sensory test

Twenty panelists were randomly assigned 1.5 ml of each of the wet tissue formulations of Examples 15 and 16 and Comparative Examples 19 and 21 by randomly changing the sides of the nose and the sides of the face of the face to apply it to the skin, And 'burning' were evaluated according to the following evaluation criteria, and the results are shown in Table 22.

Irritability

×: 0.39 or less

?: 0.4 or more and 1.0 or less

O: not less than 1.1 and not more than 2.0

⊚: not less than 2.1, not more than 3.0

[Table 22]

As shown in Table 22, the preservative composition according to the present invention showed up to five times or more the degree of irritation such as hotness and hotness compared to the comparative example, and it was confirmed that the preservative composition can be safely applied to skin without irritation.

According to the above results, the preservative for external preparations for skin according to the present invention is not only excellent in anti-buoyancy and antibacterial activity but also good in usability and does not cause toxicity, skin irritation, irritation and allergy due to use of a chemical preservative, It has been confirmed that it is very preferable as an external preparation for skin.

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 (11)

A preservative for external preparation for skin comprising dipropylene glycol in a caprylic hydroxamic acid represented by the following formula (1).
[Chemical Formula 1]

The method according to claim 1,
The preservative may be any one or more selected from 1,2-hexanediol, 1,2-pentanediol, 1,2-octanediol, 1,2-decanediol, 1,6-hexanediol and 1,8- Of an alkanediol. ≪ / RTI >

3. The method of claim 2,
Wherein the alkane diol is any one or more selected from 1,2-octanediol, 1,2-hexanediol, and 1,2-pentanediol.
3. The method of claim 2,
Wherein the preservative comprises caprylhydroxamic acid, 1,2-hexanediol, and dipropylene glycol.
5. The method of claim 4,
Wherein the preservative comprises 1 to 50 parts by weight of caprylhydroxamic acid and 10 to 150 parts by weight of 1,2-hexanediol relative to 100 parts by weight of dipropylene glycol.
A cosmetic composition comprising a preservative for external preparation for skin according to any one of claims 1 to 5.
The method according to claim 6,
Wherein the preservative for external preparation for skin comprises 0.01 to 20% by weight of the total cosmetic composition.
The method according to claim 6,
The cosmetic composition may be in the form 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 rinse, A hair styling gel, a lubricant, a toothpaste, and a wet tissue.
A pharmaceutical composition for external application for skin comprising a preservative for external preparation for skin according to any one of claims 1 to 5.
10. The method of claim 9,
Wherein the preservative for external preparation for skin is contained in an amount of 0.11 to 20 wt% of the total pharmaceutical composition.
10. The method of 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 emulsion, a lotion agent, an aerosol agent and a suppository.