KR20070098116A - Topical formulation for the treatment of dermatological conditions - Google Patents

Abstract

A topical formulation for the treatment of skin diseases is provided to inhibit growth of acne-causing bacteria and atopic dermatitis-causing bacteria by regulating pH of the composition to predetermined pH ranges with citric acid. A topical formulation for the treatment of bacterial skin diseases including acnes and atopic dermatitis comprises 0.2-9.5 wt.% of citric acid and optionally 0.1-15.5 wt.% of sodium triphosphate, has pH 3-10, and is formulated as cream, emulsion, gel or ointment.

Description

External composition for the treatment of bacterial skin diseases {TOPICAL FORMULATION FOR THE TREATMENT OF DERMATOLOGICAL CONDITIONS}

The present invention relates to an external composition for treating bacterial skin diseases, and more particularly, by adjusting the pH of the composition to a specific range using citric acid or a mixture of citric acid and sodium triphosphate, acne-inducing bacteria and a kind of bacterial skin disease. Since it can effectively inhibit the growth of atopic dermatitis-inducing bacteria, when applied to the external composition of a variety of formulations can be used to obtain an effective therapeutic effect in the treatment of acne and atopy.

Most acne and some atopic dermatitis are bacterial diseases caused by bacteria are typical diseases.

Background Art Conventionally, steroid agents such as corticosteroids having high anti-inflammatory action have been mainly used for the treatment of dermatitis such as atopic dermatitis. Steroids of this kind are added with petrolatum, methyl cellulose, surfactants, synthetic resin emulsions, powders and the like, and a lot of creamy ones are used depending on the purpose of use. In addition, there is also a form in the form of a liquid containing a surfactant.

On the other hand, as another external agent, there is a high safety solvent for the purpose of (1) skin sterilization, disinfection action, (2) film action, (3) prevents evaporation of skin moisture and promotes moisturization. Examples of external preparations of this kind include those using inorganic salts such as sodium chloride (USP 3574854), those using natural sugars such as glucose (USP 3859436), or plasma (USP 3777597). It is used as a compounding material.

In addition, conventionally, there is an external preparation for treating dermatitis that is effective for atopic dermatitis and has a very high safety. According to the therapeutic external preparation, the adrenal cortical steroid is enclosed with cyclodextrin and polysaccharide of dextran or pullulan is used. It is a therapeutic external preparation that does not impair the physiological function of the skin and obtains the natural healing power of the living body itself and the synergistic effect of the corticosteroid.

By the way, corticosteroids have high pharmacological effects, such as inhibiting the proliferation of fibroblasts and exhibiting anti-inflammatory effects, but do not show a great effect in the treatment of atopic dermatitis. Although the cause is unknown, it is caused by the oil for forming into ointment or cream form, and it is presumed that this oil dissolves the stratum corneum of the skin and prevents healthy skin regeneration.

In addition, a large amount of adrenal corticosteroids may cause side effects such as suppression of pituitary and adrenal cortex functions, and dysfunction of other organs and eyes. In order to solve this problem, it is desirable to reduce the amount of steroid agents currently used and to leave high pharmacological effects as anti-inflammatory agents.

On the other hand, acne is known to be caused by a combination of a variety of causes. In general, acne has increased secretion of sebaceous glands due to increased male hormone function in puberty, and epithelial cells of hair follicles cause abnormal keratosis and blockage of hair follicles, which leads to the formation of scleroderma, the primary lesion of acne, and anaerobic skin that resides in hair follicles. It is recognized that Propionibacterium acnes (Acne), a fungus (normal herb), actively proliferates to produce free fatty acid, which stimulates hair follicles and causes inflammation of acne. This progression of acne is exacerbated by sebum oversecretion associated with 5-alpha-reductase.

Conventionally, as a method for treating or alleviating acne, a method of using female hormones such as estrogen, which is a male hormone inhibitor, or an antimicrobial agent, has been used to suppress sebum hypersecretion. In recent years, a method of inhibiting sebum hypersecretion using a 5-alpha-reductase inhibitor has been proposed.

However, the method of using the female hormone agent is highly susceptible to skin inflammation as a side effect during the treatment of acne, and the use of female hormone has been reported as a result of the long-term administration of female hormone has been refrained from use. In addition, typical antimicrobial agents for acne bacteria include resorcinol, sulfur, benzoyl peroxide, tetracycline, erythromycin or methacycline, but the use of such antimicrobial agents may improve acne to some extent, There are many problems in terms of side effects. For example, retinoic acid and benzoyl peroxide, which are antimicrobial agents, are highly susceptible to skin irritation and contact dermatitis, and antibiotics containing tetracycline have been reported to have side effects due to the appearance of resistant bacteria and photosensitive effects.

Recently, in order to overcome the problems described above, cosmetic compositions for improving acne skin using natural fragrance substances such as tea tree oil or rosemary oil have been proposed. Has an irritating odor, making it unacceptable to consumers' tastes.

Therefore, the inventors of the present invention have tried to solve the above problems and to find a composition that can exhibit a preventive and therapeutic effect on acne and atopic dermatitis in a simple manner.

As a result, when citric acid or a mixture of citric acid and sodium triphosphate is used, especially when a mixture of citric acid and sodium triphosphate is used with a pH adjusted to a specific range, the use of citric acid or sodium triphosphate alone is higher. The present invention was found to exhibit a high antimicrobial effect to Propionibacterium acne, which is known as an acne causing bacterium, and S. aureus, which is known to cause atopic dermatitis. Completed.

Accordingly, the present invention provides an external composition for treating bacterial skin diseases effective in the treatment and prevention of acne and atopic dermatitis by a simple method of mixing citric acid or a mixture of citric acid and sodium triphosphate into a commonly used skin external preparation. There is a purpose.

The present invention is an external composition for skin, citric acid is included for the prevention and treatment of bacterial skin diseases, the pH of the external composition for skin containing citric acid may range from 3 to 10.

In addition, the external composition for skin includes sodium triphosphate, the pH of the external composition for skin containing the citric acid and the sodium triphosphate may range from 3 to 10.

In addition, the composition for external application of skin may contain 0.2 to 9.5 wt% of citric acid in 100 wt% of the total composition.

In addition, the external composition for skin, the trisodium phosphate may be contained in 0.1 to 15.5% by weight of 100% by weight of the total composition.

In the present invention, the bacterial skin disease may be acne or atopic dermatitis, and the external composition for skin may be formulated in any one formulation selected from creams, emulsions, gels and ointments.

That is, according to the present invention, the composition for external application of the skin includes citric acid and sodium triphosphate for the prevention and treatment of bacterial skin diseases, the citric acid is contained 0.2 ~ 9.5% by weight of the total 100% by weight of the composition, Sodium triphosphate is contained in an amount of 0.1 to 15.5% by weight of the total 100% by weight of the composition, the external composition of the skin has a pH range of 4.5 to 8, the composition for external application of the skin in any one of the formulation selected from cream, emulsion, gel and ointment Can be formulated.

Hereinafter, the present invention will be described in detail.

The composition for treating and preventing bacterial skin diseases of the present invention is the growth of acne-inducing bacteria and atopic dermatitis-causing bacteria, which are a type of bacterial skin disease when the pH of the composition is adjusted to a specific range using citric acid or a mixture of citric acid and sodium triphosphate. Since it can be effectively suppressed when applied to external compositions of various formulations can be used to obtain an effective therapeutic effect in the treatment of acne and atopic dermatitis.

In the "oral composition for inhibiting bad breath," which the applicant has filed earlier, the applicant has a first agent including an acidic pH adjusting agent such as citric acid tartaric acid, boric acid, phosphoric acid, hydrochloric acid, and sodium monophosphate, sodium diphosphate dibasic, sodium triphosphate tribasic. Excellent anti-odor effect by using a second agent containing basic pH adjusting agent such as sodium citrate, sodium stannate, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium pyrophosphate, calcium pyrophosphate, ethylenediaminetetraacetate disodium (EDTA 2Na) Inventive oral compositions have been invented.

In addition, the pH adjusters used in these inventions are those that have already been proven safe in the components that have been commonly used in oral compositions.

As described above, when the pH is adjusted to a specific range by mixing citric acid alone or citric acid and sodium triphosphate, the antimicrobial effect is found to have an effective effect on skin diseases caused by bacteria. That is, the composition for treating and preventing bacterial skin diseases of the present invention is added 0.2 to 9.5% by weight of citric acid in 100% by weight of the composition for external application for skin, and the total composition by adding sodium triphosphate thereto The pH of the water is adjusted to be in the range of 3 to 10, more preferably in the range of 4.5 to ８. In the present invention, the mixture of citric acid and sodium triphosphate is more preferably adjusted so that the pH range of the composition is in the range of 3 to 10 when formulated by applying to an external composition for skin. This is because when the pH of the composition is less than 3 may irritate the skin mucosa, and if the pH exceeds 10 it also causes a problem that can irritate the skin mucosa.

On the other hand, when the pH range of the composition is configured to belong to the range 4.5 to 8 it can be seen that the bacteriostatic action is made in a shorter time.

In addition, when the citric acid is contained in 0.2 ~ 9.5% by weight of the total composition 100% by weight of the composition for external skin, containing less than 0.2% by weight of citric acid as a minor weight to the total weight of the resulting skin disease treatment Is not achieved properly.

In addition, when included in excess of 9.5% by weight of the total 100% by weight may cause problems in the formulation and pH control with other compositions.

On the other hand, the trisodium phosphate may be contained 0.1 to 15.5% by weight of the total 100% by weight of the composition, as in the case of containing less than 0.1% by weight like citric acid is not effective in treating skin diseases, more than 15.5% by weight If contained, problems with the formulation and pH control with other compositions may occur.

The composition for the treatment and prevention of bacterial skin diseases of the present invention is prepared in various formulations by adding to citric acid and sodium triphosphate to the composition for external skin such as creams, emulsions, gels and ointments to the composition commonly used as an external skin. Can be used.

Hereinafter, the composition for treating and preventing bacterial skin diseases of the present invention will be described in detail with respect to each component, for example, a cream, an emulsion, a gel and an ointment in an external skin composition, but the scope of the present invention is not limited thereto.

That is, it contains a mixture of citric acid and sodium triphosphate as essential components and the pH is adjusted by these components, in addition to the various components that are commonly used as components of the external preparation for skin, such as emulsions, emulsifiers, moisturizers, thickeners, surfactants, Preservatives, functional physiologically active ingredients, chelating agents, antioxidants, antibacterial agents, perfumes, solvents, and the like can be used.

The emulsion may be used a variety of components that can be commonly used as a constituent of the external preparation for skin, such as cosmetics, for example avocado oil, linseed oil, almond oil, pewter, perilla oil, olive oil, cacao oil, panya wax, non-tree Oil, carnava wax, cod liver oil, canterilla wax, beef tallow, beef thigh, beef thigh, hardened tallow, apricot seed oil, whale wax, hardened oil, wheat germ oil, sesame oil, rice germ oil, rice bran oil, sugar cane wax, sanda oil , Sunflower oil, shea butter, mulberry oil, cinnamon oil, jojoba wax, shellac wax, turtle oil, soybean oil, fruit oil, camellia oil, evening primrose oil, corn oil, pork oil, rapeseed oil, Japanese paulownia oil, rice bran Wax, germ oil, marzipan, apricot oil, palm oil, palm kernel oil, castor oil, hardened castor oil, castor oil fatty acid methyl ester, sunflower oil, grape oil, laurel wax, jojoba oil, macadamia nut oil, beeswax, Crude oil, cottonseed oil, cotton wax, wax, beeswax kernel oil, montan wax, palm oil, hardened palm oil, tri palm oil fatty acid glyceride, oil oil, peanut oil, lanolin, liquid lanolin, reduced lanolin, lanolin alcohol, hard lanolin, lanolin acetate, lanolin Fatty acid isopropyl, hexyl lauric acid, POE lanolin alcohol ether, POE lanolin alcohol acetate, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, egg yolk oil and the like; Hydrocarbon oils include ground wax, squalane, ceresin, paraffin, paraffin wax, liquid paraffin, pristane, polyisobutyrene, microcrystalline wax, petrolatum and the like; Higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), iso Stearic acid, 12-hydroxystearic acid and the like; Higher alcohol type emulsions include lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, behenyl alcohol, hexadecyl alcohol, oleyl alcohol, isostearyl alcohol, hexyl dodecanol, octyldodecanol, and ceto Stearyl alcohol, 2-decyltetradecinol, cholesterol, phytosterol, POE cholesterol ether, monostearyl glycerine ether (betayl alcohol), monooleylglyceryl ether (selacyl alcohol) and the like; Examples of the ester oil include diisobutyl adipic acid, 2-hexyldecyl adipic acid, di-2-heptyl undecyl adipic acid, N-alkyl glycol monoisostearic acid, isocetyl isostearic acid, trimethylolpropane triisoolate, and di-2- Ethylene glycol ethylene glycol, 2-ethylhexanoic acid cetyl, tri-2-ethylhexanoic acid trimethylolpropane, tetra-2-ethylhexanoic acid pentaerythritol, octanoic acid cetyl, octyldodecyl gum ester, oleic acid oleyl, oleic acid Octyldodecyl monohydrate, decyl oleate, isononyl isononate, dipentane neopentylglycol, triethyl citrate, 2-ethylhexyl succinate, amyl acetate, ethyl acetate, butyl acetate, isocetyl stearate, butyl stearate, sebacic acid Diisopropyl, di-2-ethylhexyl sebacic acid, cetyl lactate, myristyl lactic acid, isopropyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2- palmitate Heptylundecyl, 12-hydroxystearyl acid cholesteryl, dipentaerythryl fatty acid ester, myristic acid isopropyl, myristic acid octyldodecyl, myristic acid 2-hexyldecyl, myristic acid myristyl, Hexyl dimethyl octanoate, ethyl laurate, hexyl laurate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, diisostearyl malic acid, etc .; As glyceride oil, acetoglyceryl, glyceryl triisooctanoate, glyceryl triisostearate, glyceryl triisopalmitate, glyceryl tri (caprylic capric acid), glyceryl monostearate, glycerol di-2-heptyl undecanoate Reels, trimyristinic acid glyceryl, myristic acid isostearic acid diglyceryl, and the like.

As the emulsifier, an emulsifier generally used in the art may be used, and a nonionic silicone-based surfactant, for example, branched silicone type polyglyceryl modified silicone, branched silicone type polyether modified silicone, alkyl polyether, etc. One or more of co-modified silicone, polyether-modified silicone, cross-linked polyglyceryl-modified silicone, sugar-modified silicone, and glyceryl-modified silicone can be blended, and especially branched silicone-type polyglyceryl-modified silicone and branched silicone One or more types selected from the group consisting of type polyether modified silicone, alkyl polyether comodified silicone, polyether modified silicone and crosslinked polyglyceryl modified silicone are preferred.

As the moisturizing agent, for example, sugar alcohols such as sorbitol, maltose, maltitol and the like, cholesterol, cytosterol, phytosterol, lanosterol and the like as sterols, sugars such as glucose, sucrose, lactose, raffinose, trehalose and xylitol, glycerin, Propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, 1,3-butylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, diglycerine, polyglycerol, hyaluronic acid and salts thereof, chondroitin sulfate and its Salt, pyrrolidone carbonate, polyoxyethylene methyl glucoside, polyoxypropylene methyl glucoside, ethyl glucoside and the like.

Examples of the thickener include gum arabic, tragacanth, arabinogalactan, locust bean gum (carob gum), guar gum, karaya gum, carrageenan, pectin, agar, quinseed (quincelo), starch (rice, corn, potato) , Wheat), plant-based polymers such as algocolloid, transcript gum, locust bean gum, microorganism-based polymers such as xanthan gum, dextran, succinoglucan, pullulan, animal-based macromolecular polymers such as collagen, casein, albumin, gelatin, Starch-based polymers such as carboxymethyl starch and methyl hydroxypropyl starch, methyl cellulose, ethyl cellulose, methyl hydroxypropyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, nitrocellulose, sodium cellulose sulfate, carboxymethyl cellulose Sodium, crystalline cellulose, cellulose-based cellulose polymers, sodium alginate, propylene glycol esters such as alginate Vinyl polymers such as alginic acid polymers, polyvinyl methyl ether, polyvinylpyrrolidone, and carboxyvinyl polymers, polyoxyethylene polymers such as polyethylene glycol, polyoxyethylene polyoxypropylene copolymer system polymers, sodium polyacrylate, polyethyl And acrylic thickeners such as acrylate and polyacrylic acid amide, polyethyleneimine, cationic polymer, bentonite, aluminum magnesium silicate, laponite, smectite, saponite, hectorite, silicic anhydride and the like. Other thickeners include oil-soluble gelling agents, for example, metal soaps such as aluminum stearate, magnesium stearate and zinc myristate, N-lauroyl-L-glutamic acid, α, γ-di-n- Dextrin fatty acid esters such as amino acid derivatives such as butylamine, dextrin palmitate ester, dextrinstearic acid ester, dextrin 2-ethylhexanoic acid palmitate ester, sucrose fatty acid ester such as sucrose palmitic acid ester and sucrose stearic acid ester, monobenzylidene sorbitol, Selected from the group consisting of benzylidene derivatives of sorbitol such as dibenzylidene sorbitol, organic modified clay minerals such as dimethylbenzyldodecyl ammonium montmorillonite clay, dimethyl dioctadecyl ammonium montmorillonite and octadecyldimethylbenzyl ammonium montmorillonite Use one or more gelling agents can do.

As said surfactant, in addition to the nonionics mentioned above, anionic and cationic things can be used suitably according to the kind of preparation. Examples of the anionic surfactants include fatty acid soaps such as sodium stearate and triethanolamine, alkyl ether carboxylic acids and salts thereof, carbonic acid salts such as condensation of amino acids and fatty acids, alkyl sulfonic acids, alkenesulfonates, sulfonates of fatty acid esters and fatty acid amides. Sulfonates, alkylsulfonates and their formalin condensates, sulfonates, alkylsulphate ester salts, secondary secondary alcohol sulfate ester salts, alkyl and arylethersulphate ester salts, fatty acid ester sulfate salts, fatty acid alkylolamide sulfates Sulfuric acid ester salts such as ester salts and lot oils, alkyl phosphates, ether phosphates, alkylaryl ether phosphates, amide phosphates, N-acylamino acid activators and the like; Examples of the cationic surfactant include amine salts such as alkylamine salts, polyamines and aminoalcohol fatty acid derivatives, alkyl quaternary ammonium salts, aromatic quaternary ammonium salts, pyridium salts, and imidazolium salts.

As said preservative, a paraoxy benzoic acid alkyl ester, benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, phenoxyethanol, etc. can be used selectively.

Examples of the antimicrobial agents include benzoic acid, salicylic acid, phenolic acid, sorbic acid, paraoxybenzoic acid alkyl esters, parachlormethcresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, trichromic acid, photosensitizer, phenoxyethanol and the like. There is this.

As said physiologically active component, the substance which gives a certain physiological activity to skin, when apply | coated to skin is mentioned. For example, anti-inflammatory, anti-aging, sunscreen, astringent, antioxidant, hair regrowth, hair restorer, moisturizer, blood circulation accelerator, antimicrobial agent, bactericide, desiccant, cold sensitizer, warming agent, vitamins, amino acids, wound healing accelerators, stimulants , Analgesics, cell-activating agents, enzyme components and the like.

Among these, natural plant extract components, seaweed extract components, and herbal components are particularly preferred. In this invention, it is preferable to mix | blend one type or two types or more of these bioactive components.

As these physiologically active ingredients, for example, fresh vinegar extract, avocado extract, wild hydrangea extract, pink saucer extract, arnica extract, aloe extract, apricot extract, apricot seed extract, ginkgo extract, fennel extract, turmeric extract, olongcha extract, cedar extract Lychee extract, Echinacea extract, vasta extract, yellow bark extract, Ouren extract, barley extract, red pepper extract, clown mustache extract, watercress extract, orange extract, seaweed dry, seaweed extract, hydrolyzed elastin, hydrolysis Flour powder, hydrolyzed silk, caromomile extract, carrot extract, cedar mugwort extract, licorice extract, carcass extract, piracanda extract, kiwi extract, kina extract, cucumber extract, guanosine, gardenia extract, bleacher Extract, Rhododendron Extract, Grapefruit Extract, Crema Extract, Chlorella extract, Mulberry extract, Gentiana extract, Black tea extract, Yeast extract, Burdock extract, Rice bran fermentation extract, Rice germ oil, Camphor extract, Collagen, Bilberry extract, Sessin extract, Seaho extract, Umbilical extract, Salvia extract Extract, Schwart Extract, Sparrow Extract, Hawthorn Extract, Japanese Herb Extract, Shiitake Extract, Foxroot Extract, Root Extract, Perilla Extract, Basswood Extract, Maple Grass Extract, Sesame Seed Extract, Iris Root Extract, Birch Extract Extract, horsetail extract, vine cane extract, hawthorn extract, black elderberry extract, western yarrow extract, western peppermint extract, sage extract, mallow extract, scorpion extract, siberian snake dragon extract, soybean extract, juju棗) extract, thyme extract, tea extract, clove extract, strip extract, dermis extract, Ear extract, sugar extract, Doin extract, sesame extract, three hundred sec extract, tomato extract, natto extract, carrot extract, garlic extract, wild rose extract, hibiscus extract, macmundong extract, lotus extract, parsley extract, bee extract , Hamamelis extract, Parietari extract, Bangalore extract, bisabolol, loquat, Kanto extract, Butterbur extract, Revenant extract, Rucus extract, Grape extract, Propolis, Hechima extract, Safflower extract, Peppermint extract Extract, bodhi tree extract, peony extract, hop extract, pine extract, horse chestnut extract, horse chestnut extract, green leaf extract, melissa extract, peach extract, cornflower extract, eucalyptus extract, pancreas, citron extract, ui extract Lavender extract, apple extract, lettuce extract, lemon extract, self-extracted extract, raw Grape extract, rosemary extract, chamomile extract, royal jelly extract, and the like.

In addition, biopolymers such as deoxyribonucleic acid, mucopolysaccharides, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, kitchen, chitosan, hydrolyzable membranes, glycine, valine, leucine, isoleucine, serine, threonine, phenylalanine, Amino acids such as arginine, lysine, asparic acid, glutamic acid, cystine, cysteine, methionine, tryptophan, hormones such as estradiol, ethenylestradiol, amino acids, sodium lactate, urea, sodium pyrrolidone carbonate, betaine, whey Moisturizing ingredients such as, sphingolipids, ceramides, cholesterol, cholesterol derivatives, oily ingredients such as phospholipids, ε-aminocaproic acid, glycyritinic acid, β-glytiletinic acid, lithium chloride, guazulene, hydrocorti Anti-inflammatory agents such as zone, allantoin, tranexamic acid, azulene, vitamin A, B2, B6, C, D, E, pantothenate calcium, biotin, nicotinic acid amide, vitamin C Vitamins such as stear, allantoin, diisopropylamine dichloroacetate, active ingredients such as 4-aminomethylcyclohexanecarboxylic acid, tocopherol, carotenoids, flavonoids, tannins, liguanans, saponins, butylhydroxyanisole, dibutyl Antioxidants such as hydroxytoluene and pichinic acid, cell activators such as α-hydroxy acid and β-hydroxy acid, blood circulation promoters such as γ-olizanol and vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, Separantin, Conical Extract, Capsicum Tincture, Hynothiol, Iodide Garlic Extract, Pyridoxine Hydrochloride, d1-α-Tocopherol, D1-α-Tocopherol Acetate, Nicotinic Acid, Nicotinic Acid Derivative, Calcium Pantothenate, D-Pantothenyl Alcohol, Acetyl Pantothenyl Ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethynyl esteradiol, capronium chloride, benzalkonium chloride, diphenhydramine, tacanal, camphor, salal Refreshing agents such as nitric acid, vanyrylamide, nonanilic acid vanyrylamide, pyrotonolamine, pentadecanoic acid glyceryl, 1-menthol, camphor, mononitroguayacol, resorcin, γ-aminolactic acid, γ- Amino-β-hydroxylactic acid, benzenetonium chloride, methoxyretin hydrochloride, auxin, female hormone, canthalistine, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, monostearic acid polyoxyethylene sorbitan, peppermint oil, sasa Hair restorers, such as Nishiki extract, etc. are mentioned.

Examples of the chelating agent include alanine, sodium edetate salt, sodium polyphosphate, sodium metaphosphate, and phosphoric acid.

Examples of the solvent include hard flow isoparaffins, ethers, LPG, N-methylpyrrolidone, and the like, in addition to water such as purified water, mineral water and deep sea water.

Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited only to these examples.

Experimental Example  1: Confirmation of the antimicrobial effect of citric acid and sodium triphosphate mixture on atopic dermatitis-inducing bacteria

Based on Brain Heart Infusion (BHI) medium using Staphylococcus aureus (ACC (American Type Culture Collection) 6538), one of the causative agents of atopic dermatitis, as shown in Table 1 below. After culturing in a culture medium, the number of viable cells was measured over time (UV spectrometer, 420 nm wavelength), and the results are shown in Table 1 below. Dilution of the medium for measuring the optical density (O.D) for viable cell count was diluted 10-fold with saline.

       Badge time Badgecontrol A B C D E 2 hours 0.000 0.042 0.005 0.011 0.024 0.042 4 hours 0.000 0.042 0.006 0.010 0.044 0.154 6 hours 0.002 0.033 0.005 0.011 0.071 0.346 8 hours 0.000 0.037 0.026 0.012 0.137 0.405 10 hours 0.001 0.042 0.041 0.011 0.196 0.421 12 hours 0.001 0.041 0.081 0.008 0.215 0.425 27 hours 0.001 0.035 Full growth 0.008 Full growth Full growth  A: CA 0.8g / 100ml medium + TSP 2g / 100ml medium pH 6.0 B: TSP 2g / 100ml + 5N HCl to adjust pH to 6.0 C: CA 0.8g / 100ml medium + 5N NaOH to pH 6.0 D: 5N PH to 6.0 with HCl E: BHI media control pH 7.38

The medium used in Table 1 is an example in which the amount of citric acid is used as 0.8 g in 100 ml of the medium.

According to the results of Table 1, there was no growth of bacteria in the A and C medium containing citric acid for up to 27 hours, and D medium in which pH was adjusted to hydrochloric acid for up to 12 hours in B medium containing sodium triphosphate, Compared to E medium using only BHI medium itself, it can be seen that the growth rate of bacteria was significantly reduced.

In particular, it can be seen that the degree of growth inhibition of the bacteria is greater in A medium using citric acid and sodium triphosphate.

Experimental Example  2: Confirmation of the Antimicrobial Effect of Citric Acid and Trisodium Phosphate on Atopic Dermatitis

The medium is the same as in Table 1, but the amount of citric acid is adjusted to 0.4 g, the pH of the medium is adjusted to 6.0, and the same atopic dermatitis-inducing bacteria Staphylococcus aureus (A. American Type Culture) Collection) 6538) was measured and the change in viable cell number with incubation time (UV spectrometer, 420 nm wavelength), and the results are shown in Table 2 below.

      Badge time Badgecontrol A B C D E 2 hours 0.000 0.009 0.018 0.008 - - 4 hours -0.001 -0.002 0.011 -0.002 0.016 0.042 6 hours 0.000 -0.003 0.069 0.001 0.057 0.176 8 hours 0.000 0.031 0.205 0.024 0.160 0.393 10 hours 0.001 0.030 0.273 0.033 0.242 0.408 12 hours 0.000 0.038 0.297 0.024 0.263 0.396 14 hours 0.000 0.038 0.315 0.041 0.274 0.385 18 hours 0.000 0.039 0.311 0.034 0.274 0.396 20 hours 0.000 0.037 0.292 0.022 0.250 ND 38 hours 0.000 0.038 Full growth 0.067 ND ND 48 hours 0.002 0.064 ND 0.067 ND ND 56 hours 0.000 0.123 ND 0.116 ND ND 60 hours 0.000 0.133 ND 0.137 ND ND 68 hours 0.000 0.144 ND 0.143 ND ND 76 hours 0.000 0.150 ND 0.165 ND ND  A: pH of citric acid (CA) 0.4g / 100ml + TSP 0.62g pH 6.0 B: Adjust pH to 6.0 with TSP 0.62g + 5N HCl C: Adjust pH to 6.0 with CA 0.4g / 100ml + 5N NaOH D: Addition Only pH is adjusted to 6.0 with 5N HCl (pH 7.37 before adjustment) E: BHI broth with pH 7.37 is used as a control * ND; not done, no full measurement required.

According to Table 2, there was no visible growth of Staphylococcus aureus for 48 hours in A medium and C medium containing citric acid, but significant difference in B, D and E medium without addition of citric acid. Staphylococcus aureus grew innumerably without.

Experimental Example 3: Confirming the antimicrobial effect of citric acid and trisodium phosphate mixture against acne-causing bacteria

Prophyronibacterium acne known as acne-causing bacteria (Strain: Propionibacterium acne, Korean Collection for Type Cultures (KCTC) 3314), and Wilkins Chalgren Anaerobe Broth Based on the incubation in a medium adjusted as shown in Table 3, and then measured the number of viable cells changes over time (UV spectrometer, 420 nm wavelength), the results are shown in Table 3 below.

      Badge time Badgecontrol A B C D E 4 hours 0.000 0.013 0.002 0.012 0.007 0.000 8 hours 0.000 0.011 0.004 0.013 0.010 0.002 12 hours 0.000 0.013 0.028 0.011 0.024 0.023 16 hours 0.000 0.012 0.136 0.015 0.158 0.141 20 hours 0.000 0.014 0.323 0.008 0.357 0.357 24 hours 0.000 0.011 0.387 0.005 0.431 0.323  A: citric acid 0.8g / 100ml medium + trisodium phosphate 1.85g / 100ml medium pH 6.0 B: TSP 1.85g + 5N HCl to adjust pH to 6.0 C: CA 0.8g + 5N NaOH to pH 6.0 D: 5N Adjust pH only to 6.0 with HCl E: medium control pH 7.13

As shown in Table 3, it can be confirmed that there is a high bacteriostatic (or bactericidal) effect in A and C medium using citric acid.

Experimental Example 4: Confirming the antimicrobial effect of citric acid and sodium triphosphate mixture against acne-causing bacteria

The medium is the same as in Table 3, but after adding the amount of citric acid fixed to 0.4 g, the pH of the medium is adjusted to 6.0, using the same acne-inducing bacteria, Propyronibacterium acne, Wilkins medium (Wilkins Chalgren Anaerobe Broth) ) Was cultured in a medium adjusted as shown in Table 3 below, and the change in viable cell number was measured over time (UV spectrometer, 420 nm wavelength), and the results are shown in Table 4 below.

Badge time Badgecontrol A B C D E 6 hours 0.000 0.019 0.032 0.008 0.028 0.030 10 hours 0.000 0.010 0.067 0.017 0.070 0.056 14 hours 0.000 0.029 0.171 0.034 0.164 0.141 18 hours 0.000 0.049 0.373 0.076 0.362 0.331 22 hours 0.000 0.089 0.434 0.146 0.484 0.391 32 hours 0.000 0.155 ND * 0.228 ND ND 40 hours 0.000 0.369 ND 0.262 ND ND 64 hours 0.000 0.348 ND 0.347 ND ND 88 hours 0.000 0.310 ND 0.328 ND ND  A: pH of citric acid 0.4g + trisodium phosphate 0.81g pH 6.0 B: Adjust pH to 6.0 with TSP 0.81g + 5N HCl C: Adjust pH to 6.0 with citric acid 0.4g + 5N NaOH D: pH only 6.0 with 5N HCl Adjusted with E: medium control pH 7.13 * ND; not done, no full measurement required.

As shown in Table 4, in the A and C medium prepared by adding citric acid at a rate of 0.4 g in 100 ml of medium, significant growth inhibition of bacteria was observed up to 14 hours, but gradually after 22 hours, C, D and E medium. There was no difference.

Example  1-2: cream manufacture

Next, the composition of the cream formulation was prepared by emulsifying well in a mixer at a composition ratio described in Table 5, degassing, filtration, and cooling. After the addition of other additives, such as preservatives, fragrances, pigments, etc., was prepared in the oil-in-water type (O / W) so that an oily component of a small size is present. The pH of the prepared composition was measured using a conventional pH meter and the results are shown in Table 5.

Raw material name (% by weight) Example 1 Example 2 Stearic acid 8.0 8.0 Stearyl alcohol 4.0 4.0 Butyl stearate 6.0 6.0 Propylene glycol 5.0 5.0 Citric acid 0.8 1.0 Trisodium Phosphate 1.6 1.8 Glycerin Monostearate 2.0 2.0 Potassium hydroxide 0.4 0.4 Pigment Quantity Quantity Spices Quantity Quantity antiseptic Quantity Quantity Purified water To 100 To 100 pH 6 6

Experimental Example 5: Measurement of the antimicrobial activity of the cream

2 ml of the test solution diluted and suspended in 19 g of sterile phosphate buffer solution 1 g of the cream of Examples 1 to 2 18 ml of BHI (Brain Heart Infusion) agar medium and 18 ml of Wilkins Chalgren Anaerobe Broth agar medium Was poured into a 9 cm petri dish. Subsequently, the test bacteria were inoculated with S. aureus (ATCC 6538) and Propyronibacterium acne (KCTC 3314), respectively, and Staphylococcus aureus (S. aureus, ATCC 6538). ) Was aerobic culture in a general incubator, and propironibacterium acne (KCTC 3314) was incubated for 96 hours at 37 ℃ using an anaerobic chamber (Bactron I. anaerobic chamber). The antimicrobial activity was measured by measuring the change in viable cell number over time, and the results are shown in Table 6 below.

Test bacteria Test subject Viable cell count (microbial count / ml) 0 hours 24 hours Staphylococcus aureus (S. aureus) Example 1 6.4 × 10 ⁵ / ml 6.2 × 10 ⁵ / ml Example 2 6.3 × 10 ⁵ / ml 6.2 × 10 ⁵ / ml Propiononibacterium acne Example 1 5.3 × 10 ⁵ / ml 5.3 × 10 ⁵ / ml Example 2 5.4 × 10 ⁵ / ml 5.3 × 10 ⁵ / ml

As can be seen from Table 6, the cream of the present invention was confirmed to be bacteriostatic when a certain time has elapsed against the acne-inducing bacteria and atopic dermatitis-inducing bacteria.

Examples 3-4: Ointment Preparation

Next, the composition ratio of the ointment formulation was prepared by emulsifying well in a mixer at a composition ratio shown in Table 7, degassing, filtration, and cooling. The pH of the prepared composition was measured using a conventional pH meter and the results are shown in Table 7.

Raw material name (% by weight) Example 3 Example 4 Aluminum hydroxychloride  20  20 glycerin  10  10 1,3-butylene glycol  3  3 Potassium hydroxide  0.25  0.25 Stearic acid  2  2 Stearic Acid Monoglycerides  2  2 Setanol  One  One Liquid paraffin  5  5 vaseline  2  2 Citric acid 1.6 1.7 Trisodium Phosphate 2.2 2.4 Ethylenediaminehydroxyethyl triacetate trisodium  0.01  0.01 Purified water  To 100  To 100 pH 6 6

Experimental Example  6: measurement of antibacterial activity of ointment

2 ml of the test solution diluted and suspended in 19 g of sterile phosphate buffer solution 1 g of Examples 3 to 4 was 18 ml of BHI (Brain Heart Infusion) agar medium and 18 ml of Wilkins Chalgren Anaerobe Broth agar medium. Was poured into a 9 cm petri dish. Subsequently, the test bacteria were inoculated with S. aureus (ATCC 6538) and Propyronibacterium acne (KCTC 3314), respectively, and Staphylococcus aureus (S. aureus, ATCC 6538). ) Was aerobic culture in a general incubator, and propironibacterium acne (KCTC 3314) was incubated for 96 hours at 37 ℃ using an anaerobic chamber (Bactron I. anaerobic chamber). Antimicrobial activity was measured by measuring the change in viable cell number over time, and the results are shown in Table 8 below.

Test bacteria Test subject Viable cell count (microbial count / ml) 0 hours 24 hours Staphylococcus aureus (S. aureus) Example 3 6.4 × 10 ⁵ / ml 6.1 × 10 ⁵ / ml Example 4 6.3 × 10 ⁵ / ml 6.0 × 10 ⁵ / ml Propiononibacterium acne Example 3 5.3 × 10 ⁵ / ml 5.2 × 10 ⁵ / ml Example 4 5.4 × 10 ⁵ / ml 5.2 × 10 ⁵ / ml

As can be seen from Table 8, the ointment of the present invention was confirmed to be bacteriostatic when a certain time has elapsed against the acne-inducing bacteria and atopic dermatitis-inducing bacteria.

Examples 5-6: Gel Preparation

Next, the composition of the gel formulation was prepared by emulsifying well in a mixer at a composition ratio shown in Table 9, followed by degassing, filtration and cooling. The pH of the prepared composition was measured using a conventional pH meter, and the results are shown in Table 9.

Raw material name (% by weight) Example 5 Example 6 Aluminum hydroxychloride  20  20 Dipropylene glycol  5  5 PEG1500  5.5  5.5 Carboxy Vinyl Polymer 0.4 0.4 Methylcellulose  0.2  0.2 POE (15) oleyl alcohol ether  0.5  0.5 Potassium hydroxide  0.1  0.1 EDTA  0.02  0.02 Citric acid 1.6 1.7 Trisodium Phosphate 2.2 2.4 Ethylenediaminehydroxyethyl triacetate trisodium  0.01 0.01 Purified water  To 100  To 100 pH 6 6

Experimental Example 7: Measurement of the antimicrobial activity of the gel

2 ml of the test solution, which was diluted and suspended in 19 g of sterile phosphate buffer solution, 1 g of the gels of Examples 5 to 6 and Comparative Examples 7 to 9, 18 ml of BHI (Brain Heart Infusion) agar medium, and 2 ml of the test solution were Wilkins Chalgren Anaerobe. Broth) 18 ml agar medium was poured into a 9 cm petri dish. Subsequently, the test bacteria were inoculated with S. aureus (ATCC 6538) and Propyronibacterium acne (KCTC 3314), respectively, and Staphylococcus aureus (S. aureus, ATCC 6538). ) Was aerobic culture in a general incubator, and propironibacterium acne (KCTC 3314) was incubated for 96 hours at 37 ℃ using an anaerobic chamber (Bactron I. anaerobic chamber). The antimicrobial activity was measured by measuring the change in viable cell number over time, and the results are shown in Table 10 below.

Test bacteria Test subject Viable cell count (microbial count / ml) 0 hours 24 hours Staphylococcus aureus (S. aureus) Example 5 6.4 × 10 ⁵ / ml 6.1 × 10 ⁵ / ml Example 6 6.3 × 10 ⁵ / ml 6.0 × 10 ⁵ / ml Propiononibacterium acne Example 5 5.3 × 10 ⁵ / ml 5.2 × 10 ⁵ / ml Example 6 5.4 × 10 ⁵ / ml 5.2 × 10 ⁵ / ml

As can be seen from Table 10, the gel of the present invention was confirmed to be bacteriostatic when a certain time has elapsed against the acne-inducing bacteria and atopic dermatitis-inducing bacteria.

As described above, the composition for the treatment and prevention of bacterial skin diseases of the present invention can be acne simply by adjusting the pH using citric acid or a mixture of citric acid and sodium triphosphate without adding a separate herbal extract or steroid preparation. And it is possible to significantly reduce the causative agent of atopic dermatitis to provide a composition having excellent prevention and treatment efficacy of acne and atopic skin diseases.

The above-described compositions for treating and preventing bacterial skin diseases can be used without limitation to specific formulations as long as they are used as external preparations applied to the skin.

Claims (8)

As an external composition for skin, citric acid is included for the prevention and treatment of bacterial skin diseases, the external composition of the skin, characterized in that the pH of the external composition containing the citric acid ranges from 3 to 10. The composition for external application of skin according to claim 1, wherein the composition for external application for skin includes sodium triphosphate, and the pH of the external composition for skin containing citric acid and sodium triphosphate is in the range of 3 to 10. The composition for external application of skin according to claim 2, wherein the composition for external application of skin has a pH in the range of 4.5 to 8. The composition for external application of skin according to claim 3, wherein the citric acid is contained in an external composition for skin in an amount of 0.2 to 9.5% by weight in 100% by weight of the total composition. The composition for external application of skin according to claim 4, wherein the composition for external application of skin contains 0.1 to 15.5% by weight in 100% by weight of the total composition of sodium triphosphate. The composition for applying the external of the skin according to any one of claims 1 to 5, wherein the bacterial skin disease is acne or atopic dermatitis. 6. The composition for external application of skin according to any one of claims 1 to 5, wherein the composition for external application for skin is formulated in any one of a formulation selected from creams, emulsions, gels and ointments. As an external composition for skin, citric acid and sodium triphosphate are included for the prevention and treatment of bacterial skin diseases, the citric acid is contained 0.2 to 9.5% by weight of 100% by weight of the total composition, the total sodium triphosphate composition 100 It contains 0.1 to 15.5% by weight of the external composition, the pH of the external composition for skin ranges from 4.5 to 8, characterized in that the external composition for skin is formulated in any one of the formulations selected from creams, emulsions, gels and ointments. Skin external composition.