JP2012232970A - Antibacterial composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antibacterial composition that can exert practically sufficient antibacterial activity even when an azelaic acid concentration is lower than that of a conventional formulation.SOLUTION: The antibacterial composition contains 0.1-10 wt.% of soluble azelaic acid and has a pH of 2-6.5.

Description

  The present invention relates to an antibacterial composition.

Azelaic acid is widely used overseas as an active ingredient in acne treatments. Overseas, preparations such as creams and gels containing azelaic acid at a high concentration of 20% by weight are used. In addition, since azelaic acid is difficult to dissolve in a base, it is usually contained in a preparation in a dispersed state.
However, if the azelaic acid concentration in the preparation is high, irritation to the skin becomes strong, and thus a formulation design that suppresses irritation is required.

  An object of the present invention is to provide an antibacterial composition that can exhibit practically sufficient antibacterial activity even when the azelaic acid concentration is lower than that of conventional preparations.

  The present inventor repeated research to solve the above problems, and the composition containing 0.1 to 10% by weight of dissolved azelaic acid and having a pH of 2 to 6.5 has a low azelaic acid concentration. Nevertheless, it was found to have sufficient antibacterial activity.

The present invention has been completed based on the above findings, and provides the following antibacterial composition.
Item 1. An antibacterial composition comprising 0.1 to 10% by weight of dissolved azelaic acid and having a pH of 2 to 6.5.
Item 2. Item 2. The composition according to Item 1, further comprising at least one selected from the group consisting of ascorbic acid, derivatives thereof, and salts thereof.
Item 3. Ascorbic acid, derivatives thereof, and salts thereof include L-ascorbic acid, L-ascorbic acid phosphate, L-ascorbic acid-2-sulfate, L-ascorbic acid-2-glucoside, ethyl ascorbate, and Item 3. The composition according to Item 2, which is a salt of
Item 4. Item 4. The composition according to Item 2 or 3, comprising 0.1 to 20% by weight of at least one selected from the group consisting of ascorbic acid, derivatives thereof, and salts thereof with respect to the total amount of the composition.
Item 5. Item 5. The composition according to any one of Items 1 to 4, further comprising at least one kind of solubilizing agent selected from the group consisting of polyhydric alcohols, glycol ethers and derivatives thereof, and monohydric alcohols having 1 to 4 carbon atoms. object.
Item 5-2. Item 6. The composition according to Item 5, comprising 1 to 50% by weight of polyhydric alcohol relative to the total amount of the composition.
Item 5-3. Item 6. The composition according to Item 5, comprising 2 to 60% by weight of monohydric alcohol having 1 to 4 carbon atoms based on the total amount of the composition.
Item 5-4. Item 6. The composition according to Item 5, comprising 0.001 to 70% by weight of glycol ether and / or a derivative thereof based on the total amount of the composition.
Item 6. The term in which the solubilizer is at least one polyhydric alcohol selected from the group consisting of propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, diglycerin, polyethylene glycol, polypropylene glycol, and polyglycerin. The composition according to 5, or 5-2.
Item 7. Item 5. The composition according to Item 5 or 5-3, wherein the dissolution aid is ethanol.
Item 8. Item 5. The composition according to Item 5 or 5-4, wherein the dissolution aid is diethylene glycol monoethyl ether.
Item 9. Item 9. The composition according to any one of Items 5, 5-2, 5-3, 5-4, and 6-8, wherein the dissolution aid is contained in an amount of 1 to 80% by weight based on the total amount of the composition.
Item 9-2. The solubilizing agent is a combination of propylene glycol and ethanol, a combination of dipropylene glycol and ethanol, a combination of 1,3-butylene glycol and ethanol, a combination of glycerin and ethanol, a combination of diglycerin and ethanol, A combination of 1,3-butylene glycol, polyethylene glycol, propylene glycol and ethanol, a combination of 1,3-butylene glycol, glycerin and ethanol,
A combination of propylene glycol, dipropylene glycol and ethanol, a combination of propylene glycol and diethylene glycol monoethyl ether, a combination of dipropylene glycol and diethylene glycol monoethyl ether, a combination of 1,3-butylene glycol and diethylene glycol monoethyl ether, Combination of glycerin and diethylene glycol monoethyl ether, combination of diglycerin and diethylene glycol monoethyl ether, combination of propylene glycol, dipropylene glycol and diethylene glycol monoethyl ether, 1,3-butylene glycol, polyethylene glycol, propylene glycol and diethylene glycol Combination with monoethyl ether, 1,3 -A combination of butylene glycol, glycerin and diethylene glycol monoethyl ether,
Combination of propylene glycol, diethylene glycol monoethyl ether and ethanol, combination of dipropylene glycol, diethylene glycol monoethyl ether and ethanol, combination of 1,3-butylene glycol, diethylene glycol monoethyl ether and ethanol, glycerin and diethylene glycol monoethyl ether And ethanol, diglycerin and diethylene glycol monoethyl ether and ethanol, or propylene glycol, dipropylene glycol, diethylene glycol monoethyl ether and ethanol, 1,3-butylene glycol, polyethylene glycol and propylene glycol Ethanol and diethylene glycol monoethyl ether Item 10. The composition according to Item 5 or 9, which is a combination of or a combination of 1,3-butylene glycol, glycerin, ethanol and diethylene glycol monoethyl ether.

The antibacterial composition of the present invention is excellent in spite of the low azelaic acid concentration of 0.1 to 10% by weight because azelaic acid is dissolved and the pH is 2 to 6.5. Has antibacterial activity. Therefore, the antiseptic power of the composition is ensured, and symptoms caused by bacteria such as acne can be improved when used on subjects.
Moreover, since the azelaic acid concentration is low, it can be produced at low cost.

Hereinafter, the present invention will be described in detail.
The antibacterial composition of the present invention is a composition containing 0.1 to 10% by weight of dissolved azelaic acid and having a pH of 2 to 6.5.

The content of azelaic acid azelaic acid composition, relative to the total amount of the composition, about 0.1% by weight or more, preferably at least about 0.5%, about 1 wt% or more is more preferable. In this range, sufficient antibacterial power can be obtained.
The content of azelaic acid in the composition is about 10% by weight or less, preferably about 7% by weight or less, more preferably about 5% by weight or less, and still more preferably about 3% by weight or less. Within this range, the composition of the composition can be selected from a wide range in order to obtain dissolved azelaic acid. Moreover, skin irritation can be sufficiently suppressed.

Azelaic acid is dissolved in the composition. The dissolution of azelaic acid can be confirmed by magnifying it 1000 times using a microscope or a microscope, and it can be determined as a dissolved type when no azelaic acid crystals are observed.
Azelaic acid may be used in the form of a physiologically acceptable salt. Physiologically acceptable salts of azelaic acid include sodium salt, potassium salt, calcium salt, magnesium salt, zinc salt, ammonium salt, methylamine salt, pyridine salt, trimethylamine salt, triethanolamine salt, diethanolamine salt, etc. Can be mentioned. Even if it mix | blends as azelaic acid at the time of preparation of a composition, 1 type, or 2 or more types of azelaic acid salt may arise in the obtained composition.

pH
The pH of the composition of the present invention is about 2 or higher, preferably about 2.5 or higher, more preferably about 3 or higher. If it is this range, it will become a composition with little skin irritation.
The pH of the composition of the present invention is about 6.5 or less, preferably about 6.3 or less, more preferably about 6 or less. In this range, sufficient antibacterial power can be obtained.
As will be described later, when the composition of the present invention contains ascorbic acid, a derivative thereof, and / or a salt thereof, the pH is preferably about 4 or less, which suppresses coloring of the composition. .
The pH adjustment can be achieved, for example, with inorganic bases such as potassium hydroxide and sodium hydroxide, and bases such as organic bases such as triethanolamine, diisopropanolamine, and triisopropanolamine; hydrochloric acid, and sulfuric acid. Inorganic acids and acids such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, and organic acids such as sodium succinate may be used. An acid and a base can be used individually by 1 type or in combination of 2 or more types.

In order to make azelaic acid soluble, at least one solubilizing agent selected from the group consisting of polyhydric alcohols, glycol ethers or derivatives thereof, and monohydric alcohols having 1 to 4 carbon atoms is added to the composition. Is preferred.
A solubilizer can be used individually by 1 type or in combination of 2 or more types.

Polyhydric alcohols Polyhydric alcohols are generally added to cosmetics and pharmaceutical external preparations as moisturizers. In this invention, the well-known polyhydric alcohol used for cosmetics and a pharmaceutical external preparation can be used without a restriction | limiting.
As such known polyhydric alcohols,
Specifically, ethylene glycol, propylene glycol, 1,3-propanediol (trimethylene glycol), 1,2-butylene glycol, 1,3-butylene glycol, 2,3-butylene glycol, 1,4-butanediol (Tetramethylene glycol), 2-butene-1,4-diol, 1,5-pentanediol (pentamethylene glycol), 1,2-pentanediol, isoprene glycol (isopentyldiol), hexylene glycol, dipropylene glycol , Polyethylene glycol (polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene Recall 4000, dihydric alcohols such as polyethylene glycol 6000, polyethylene glycol 20000, and polyethylene glycol 35000), and polypropylene glycol (polypropylene glycol 700, polypropylene glycol 1000, polypropylene glycol 2000);
Trihydric alcohols such as glycerin and trimethylolpropane;
Diglycene; and polyglycerin and the like.

Among these, propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, and diglycerin are preferable.
Also, polyethylene glycol (for example, polyethylene glycol obtained by polymerizing about 2 to 870 ethylene glycol, especially about 2 to 84, especially about 2 to 13), polypropylene glycol (for example, about 2 to 35 propylene glycol, especially Also preferred are about 2 to 24, especially about 2 to 12, polymerized polypropylene glycol) and polyglycerin (for example, polyglycerin polymerized with about 2 to 10, especially about 7 to 10 glycerin).

When the polyhydric alcohol is included, the content of the polyhydric alcohol is preferably about 1% by weight or more, more preferably about 3% by weight or more, and still more preferably about 5% by weight or more based on the total amount of the composition. Within this range, azelaic acid can be sufficiently dissolved.
In addition, the content of the polyhydric alcohol in the case of containing the polyhydric alcohol is preferably about 50% by weight or less, more preferably about 30% by weight or less, and still more preferably about 20% by weight or less based on the total amount of the composition. preferable. Within this range, a good feeling without stickiness can be obtained.

Glycol ether or its derivatives
<Glycol ether>
Examples of the glycol ether include, but are not limited to, monoethers of ethylene glycol, diethylene glycol, propylene glycol, or dipropylene glycol and methyl alcohol, ethyl alcohol, or propyl alcohol.
Preferred glycol ethers include, for example, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, Examples include dipropylene glycol monoethyl ether and dipropylene glycol monopropyl ether. Of these, ethylene glycol monomethyl ether and diethylene glycol monoethyl ether are preferable, and diethylene glycol monoethyl ether is more preferable.

<Derivative>
Examples of the glycol ether derivatives include, but are not limited to, monoethers of ethylene glycol, diethylene glycol, propylene glycol, or dipropylene glycol and methyl alcohol, ethyl alcohol, or propyl alcohol, and one basic acid or two bases. Examples include esters with acids. Of these, esters with dibasic acids are preferred.
Examples of dibasic acids include succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, and saturated linear dicarboxylic acids such as dodecanedioic acid; 2,2,4-trimethyladipic acid, And saturated branched dicarboxylic acids such as 2,4,4-trimethyladipic acid; 1,2-cyclohexanedicarboxylic acid, 1,3-cyclohexanedicarboxylic acid, 1,4-cyclohexanedicarboxylic acid, phthalic acid, isophthalic acid, and Examples thereof include cyclic dicarboxylic acids such as terephthalic acid (alicyclic dicarboxylic acids and aromatic dicarboxylic acids).
Of these, saturated linear dicarboxylic acids, in particular, succinic acid, adipic acid, azelaic acid, sebacic acid, are excellent in the effect of promoting penetration of the composition into the skin, are easily available, and are inexpensive. And cyclic dicarboxylic acids, in particular 1,4-cyclohexanedicarboxylic acid, phthalic acid, and terephthalic acid are preferred. Of these, succinic acid, adipic acid, and 1,4-cyclohexanedicarboxylic acid are preferable, and 1,4-cyclohexanedicarboxylic acid is most preferable.
Preferred glycol ether derivatives include, but are not limited to, for example, succinic acid ester of ethylene glycol monomethyl ether, adipic acid ester of ethylene glycol monomethyl ether, 1,4-cyclohexanedicarboxylic acid ester of ethylene glycol monomethyl ether, diethylene glycol monoethyl ether Succinic acid ester, diethylene glycol monoethyl ether adipic acid ester, diethylene glycol monoethyl ether 1,4-cyclohexanedicarboxylic acid ester, and the like.

When the glycol ether and / or derivative thereof is included, the content thereof is preferably about 0.001% by weight or more, more preferably about 1% by weight or more, and more preferably about 10% by weight or more based on the total amount of the composition. Further preferred. Within this range, azelaic acid can be sufficiently dissolved.
In addition, when the glycol ether and / or derivative thereof is included, the content thereof is preferably about 70% by weight or less, more preferably about 60% by weight or less, and more preferably about 55% by weight or less based on the total amount of the composition. Further preferred. Within this range, a good feeling without stickiness can be obtained.

Lower alcohol Lower alcohol is generally added to cosmetics and pharmaceutical external preparations as a solubilizer or base. In this invention, the well-known C1-C4 monohydric alcohol used for cosmetics or a pharmaceutical external preparation can be used without a restriction | limiting.
Examples of such known monohydric alcohol having 1 to 4 carbon atoms include methanol, ethanol, propanol, isopropyl alcohol, butanol, isobutyl alcohol, sec-butyl alcohol, and tert-butyl alcohol. Of these, ethanol and isopropyl alcohol are preferable, and ethanol is more preferable.

When the monohydric lower alcohol having 1 to 4 carbon atoms is contained, the content of the lower alcohol is preferably about 1% by weight or more, more preferably about 3% by weight or more, more preferably about 5%, based on the total amount of the composition. Even more preferred is weight percent or more. Within this range, azelaic acid can be sufficiently dissolved.
In addition, when the lower alcohol is included, the content of the lower alcohol is preferably about 40% by weight or less, more preferably about 30% by weight or less, and still more preferably about 20% by weight or less based on the total amount of the composition. . If it is this range, a composition with little skin irritation can be obtained.

(i) polyhydric alcohol, (ii) glycol ether and / or derivative thereof, and (iii) monovalent lower alcohol having 1 to 4 carbon atoms, (i), (ii), and (iii) -2 The total content of these solubilizers when including the above is preferably about 2% by weight or more, more preferably about 5% by weight or more, and still more preferably about 10% by weight or more based on the total amount of the composition. Within this range, azelaic acid can be sufficiently dissolved.
Further, the total content of the solubilizing agent is preferably about 90% by weight or less, more preferably about 80% by weight or less, based on the total amount of the composition. If it is this range, the composition which does not have a problem in a usability | use_condition will be obtained.

Preferred combinations of solubilizers As described above, the composition of the present invention is preferably at least one selected from the group consisting of polyhydric alcohols, glycol ethers and derivatives thereof, and monohydric alcohols having 1 to 4 carbon atoms. (I) at least one polyhydric alcohol, (ii) at least one glycol ether, and derivatives thereof, and (iii) at least one monohydric alcohol having 1 to 4 carbon atoms. In (1), (i), (ii), and (iii) 2 are preferably included, in particular, (i) and (ii) are included, and (i) and (iii) are more preferably included. It is also preferable to include (i), (ii), and (iii). When two or more of (i), (ii), and (iii) are included, (ii) is preferably diethylene glycol monoethyl ether, and (iii) is preferably ethanol.
By including a suitable combination of polyhydric alcohol, monohydric alcohol, and glycol ether and / or a derivative thereof, azelaic acid is sufficiently dissolved and a composition having a good feeling in use is obtained.

Preferred combinations of solubilizers (alcohols, glycol ethers) are shown in Table 1 below.

Ascorbic acid, derivatives thereof, and salts thereof The composition of the present invention is further at least one selected from the group consisting of ascorbic acid, derivatives thereof, and salts thereof (hereinafter sometimes referred to as “ascorbic acids”). Is preferably included, thereby improving the antibacterial activity of the composition. Ascorbic acids themselves do not have antibacterial activity, but they enhance the antibacterial activity of azelaic acid and provide a better antibacterial action.
Moreover, the permeability of azelaic acid can be improved by including ascorbic acids. Moreover, since the composition of the present invention contains ascorbic acids, the melanin production inhibitory action, antioxidant action, and / or sebum secretion inhibitory action of each of ascorbic acids and azelaic acid is enhanced, so that acne prevention, It is effective in preventing acne deterioration and improving pigmentation of acne scars.

<Ascorbic acid>
The ascorbic acid used in the present invention is not particularly limited as long as it is used as a component of an external preparation for cosmetics, pharmaceuticals, or quasi drugs. For example, L-ascorbic acid known by the common name of vitamin C can be mentioned.

<Ascorbic acid derivative>
The ascorbic acid derivative is not particularly limited as long as it is used as a component of an external preparation for cosmetics, pharmaceuticals, or quasi drugs, as with ascorbic acid, and any ester derivative or ether derivative is used. it can. In particular, ester derivatives or ether derivatives that are water-soluble or highly water-soluble are preferred. Examples of water-soluble or highly water-soluble ascorbic acid ester derivatives include L-ascorbic acid monophosphate, L-ascorbic acid diphosphate, and L-ascorbic acid triphosphate such as L-ascorbic acid triphosphate. Examples thereof include phosphoric acid esters and L-ascorbic acid-2-sulfate. Examples of water-soluble or highly water-soluble ascorbic acid ether derivatives include ethyl ascorbate and L-ascorbic acid-2-glucoside.

<Salt of ascorbic acid or its derivative>
As salts of ascorbic acid or derivatives thereof, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium, calcium and barium, and metal salts such as polyvalent metal salts such as aluminum; Mention may be made of ammonium and ammonium salts such as tricyclohexylammonium; and alkanolamine salts such as monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, and triisopropanolamine.

  Preferable ascorbic acids include, for example, L-ascorbic acid, L-ascorbic acid phosphate, L-ascorbic acid-2-sulfate, L-ascorbic acid-2-glucoside, ethyl ascorbate, and salts thereof L-ascorbic acid, L-ascorbic acid monophosphate ester, L-ascorbic acid-2-glucoside, ethyl ascorbate, and salts thereof. Is particularly preferred.

The content of ascorbic acids is preferably about 0.1% by weight or more, more preferably about 0.2% by weight or more, and still more preferably about 0.5% by weight or more based on the total amount of the composition. If it is this range, the antibacterial power improvement effect is fully acquired.
The content of ascorbic acids is preferably about 20% by weight or less, more preferably about 10% by weight or less, and still more preferably about 5% by weight or less based on the total amount of the composition. If it is this range, irritation | stimulation to skin will be suppressed and a favorable usability will be obtained.

Formulation Form The composition of the present invention is obtained by dissolving azelaic acid in a base or carrier, adding other additives and other active ingredients as necessary, and adjusting the pH to 3 to 6.5. , Cosmetics, quasi drugs, or pharmaceutical preparations.

The form of the composition is not particularly limited, and for example, a liquid, suspension, emulsion, cream, ointment, gel, liniment, lotion, aerosol, stick, and non-woven fabric impregnated with a chemical solution Agents and the like. These preparations can be produced, for example, according to the method described in the 15th revised Japanese Pharmacopoeia General Rules for Pharmaceuticals. Of these, liquids, emulsions, creams, ointments, gels, lotions, aerosols, sticks, and sheets are preferable, and liquids, emulsions, creams, gels, lotions, and sheets are more preferable. preferable.
When an oily base and an aqueous base are included, such as creams and emulsions, they may be W / O type or O / W type, but O / W type is preferred.
Specific uses of the composition include basic cosmetics such as lotions, emulsions, gels, creams, cosmetics, sunscreens, packs, masks, hand creams, body lotions, and body creams; Cosmetics for makeup such as cosmetics, makeup removers, shaving agents, body shampoos, shampoos, rinses, and treatments; cosmetics for lips such as lip balms and lipsticks; hair removal agents; and bath preparations.

As the base or carrier, as described above, at least one alcohol selected from the group consisting of polyhydric alcohols, glycol ethers and derivatives thereof, and monovalent lower alcohols having 1 to 4 carbon atoms is used. Is preferred.
Furthermore, a known base or carrier for cosmetics, quasi-drugs, or pharmaceuticals can be added as long as azelaic acid can be dissolved. Such known bases or carriers include, for example, liquid paraffins, squalane, petrolatum, gelled hydrocarbons (such as plastibase), ozokerites, α-olefin oligomers, and hydrocarbons such as light liquid paraffins; methylpolysiloxanes, Cross-linked methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic silicone, alkyl-modified silicone, cross-linked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, cross-linked polyether-modified silicone, cross-linked alkylpoly Ether-modified silicone, silicone-alkyl chain co-modified polyether-modified silicone, silicone-alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin modification Silicone oils such as branched silicones, acrylic silicones, phenyl-modified silicones, and silicone resins; higher alcohols such as cetanol, cetostearyl alcohol, stearyl alcohol, and behenyl alcohol; sterols such as cholesterol, phytosterol, and phytosteryl hydroxystearate Vegetable oils such as jojoba oil, medofoam oil, sunflower oil, grape seed oil, grape oil, squalane, shea butter and rice germ oil; animal oils such as lanolin, orange raffie oil, squalane, and horse oil; ethyl cellulose, hydroxy Natural polymer derivatives such as propylcellulose, hydroxypropylmethylcellulose, cationized guar gum, and acetylated hyaluronic acid; polyvinylpyrrolidone, carboxy Synthetic polymers such as civinyl polymers and alkyl methacrylate copolymers; natural polymers such as carrageenan, alginic acid, cellulose, guar gum, quince seed, dextran, gellan gum, and hyaluronic acid; isopropyl myristate, myristine Esters such as octyldodecyl acid, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythritol tetra-2-ethylhexanoate, jojoba oil, and glyceryl tri (caprylate / caprate); dextrin, and maltodextrin Polysaccharides such as: organic acids such as succinic acid, glycolic acid, gluconic acid, and citric acid; and aqueous bases such as water.

  When using bases or carriers other than polyhydric alcohols, glycol ethers and derivatives thereof, and monovalent lower alcohols having 1 to 4 carbon atoms, these bases or carriers are used singly or in combination. The above can be used in combination.

Additives In the composition of the present invention, known additives added to cosmetics, quasi-drugs, or pharmaceuticals, for example, antioxidants, surfactants, thickeners, as long as the effects of the present invention are not impaired. An agent, a preservative, a pH adjuster, a stabilizer, an irritation reducing agent, an antiseptic, a coloring agent, a fragrance, a pearly luster imparting agent, and the like can be added.
Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivative, tocopherol, tocopherol derivative, erythorbic acid, and L-cysteine hydrochloride.

  Examples of the surfactant include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate. Sorbitan fatty acid esters such as propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene Hydrogenated castor oil 60 (HCO-60), and hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 80; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan nostearate (polysorbate 60), polyoxyethylene monooxylate (20) sorbitan (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate Glyceryl alkyl ethers; alkyl glucosides; polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; amines such as stearylamine and oleylamine; polyoxyethylene and methylpolysiloxane Silicone-based interfaces such as polymers, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone Natural surfactants such as phospholipids, surfactins, and saponins; fatty acid amidoamines such as diethylaminoethylamide stearate and diethylaminopropylamide stearate; trilaurylamine, dimethylstearylamine, and di-2-ethylhexylamine Alkylamines such as dimethylaminopropylamide stearate, and betaine amphoteric surfactants such as lauryl hydroxysulfobetaine.

  Examples of the thickener include guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, alkyl methacrylate copolymer, polyethylene glycol, bentonite, alginic acid, macrogol, chondroitin sulfate sodium , Hyaluronic acid, and cellulose thickeners (such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carboxyethylcellulose) and salts thereof.

  Examples of the preservatives or preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, Examples include benzyl paraoxybenzoate, methyl paraoxybenzoate, phenoxyethanol, benzyl alcohol, chlorobutanol, sorbic acid and its salts, chlorhexidine gluconate, alkanediol, and glycerin fatty acid ester.

  Examples of pH adjusters include inorganic acids (such as hydrochloric acid and sulfuric acid), organic acids (such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, and sodium succinate), inorganic bases (potassium hydroxide, And sodium hydroxide), and organic bases (such as triethanolamine, diisopropanolamine, and triisopropanolamine).

Examples of the stabilizer include edetate, sodium polyacrylate, dibutylhydroxytoluene, and butylhydroxyanisole.
Examples of the irritation reducing agent include licorice extract and sodium alginate.

  An additive can be used individually by 1 type or in combination of 2 or more types.

Other Active Ingredients The composition of the present invention can contain other active ingredients as long as the effects of the present invention are not impaired. Specific examples of active ingredients include, for example, moisturizing ingredients, anti-inflammatory ingredients, antibacterial or bactericidal ingredients, vitamins, peptides or derivatives thereof, cell activation ingredients, anti-aging ingredients, blood circulation promoting ingredients, keratin softening ingredients, whitening ingredients, Examples include an astringent component and an ultraviolet protection component.

  Examples of moisturizing ingredients include polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, dipropylene glycol, sorbitol, xylitol, erythritol, and diglycerine; glucose, maltose, and trehalose. Saccharides; high molecular weight compounds such as sodium hyaluronate, heparin analogs, sodium chondroitin sulfate, collagen, elastin, keratin, chitin, and chitosan; natural moisturizing factors such as sodium lactate and sodium pyrrolidone carboxylate; ceramide, cholesterol , And lipids such as phospholipids; plant extract extracts such as chamomile extract, hamamelis extract, tea extract, and perilla extract.

  Examples of the anti-inflammatory component include a component derived from a plant (for example, Comfrey), allantoin, glycyrrhizic acid or a derivative thereof, zinc oxide, pyridoxine hydrochloride, tocopherol acetate, and salicylic acid or a derivative thereof.

  Antibacterial or bactericidal components include, for example, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, sulfur, resorcin, ethanol, benzethonium chloride, adapalene, benzoyl peroxide, clindamycin, cresol, gluconic acid and its derivatives, popidone iodine, iodine Potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, paraben, phenoxyethanol, 1,2-pentanediol, alkanediol, glycerin fatty acid ester, alkyldiaminoglycine hydrochloride, chlorhexidine gluconate And zinc paraphenolsulfonate.

  Examples of vitamins include retinol derivatives such as retinol, retinol acetate, and retinol palmitate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, d-δ-tocopheryl retinoate, α-tocopheryl. Vitamin A such as retinoate and β-tocopheryl retinoate; vitamin E such as dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, and dl-α-tocopherol calcium succinate Riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, sodium riboflavin 5'-phosphate, and riboflavin tetranicotinate Nicotinic acids such as dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, and 1- (4-methylphenyl) ethyl nicotinate; ascorbigen-A, Vitamin Cs such as ascorbyl stearate, ascorbyl palmitate, and L-ascorbyl dipalmitate; Vitamin D such as methyl hesperidin, ergocalciferol, and cholecalciferol; Vitamin K such as phylloquinone and farnoquinone Γ-oryzanol; dibenzoyl thiamine, dibenzoyl thiamine hydrochloride; thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thia Vitamin B1 such as minlysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, and thiamine triphosphate monophosphate Vitamin B6 such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal hydrochloride, and pyridoxamine hydrochloride; Vitamin B12 such as cyanocobalamin, hydroxocobalamin, and deoxyadenosylcobalamin; folic acid, pteroylglutamic acid, etc. Folic acid; nicotinic acid such as nicotinic acid and nicotinic acid amide; pantothenic acid, pantothenic acid calcium, pantothenyl alcohol (panthenol), D-pantheine, D-pa Pantothenic acids such as tetin, coenzyme A, and pantothenyl ethyl ether; biotins such as biotin and biotisin; ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, and magnesium ascorbate phosphate And vitamin C acting ascorbic acid derivatives such as carnitine, ferulic acid, α-lipoic acid, and orotic acid.

  Peptides or derivatives thereof include, for example, keratin-degrading peptide, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptide, collagen-degrading peptide, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin Degraded peptide, conchiolin degrading peptide, hydrolyzed conchiolin, silk proteolytic peptide, hydrolyzed silk, lauroyl hydrolyzed silk sodium, soy proteolytic peptide, hydrolyzed soy protein, wheat protein, wheat proteolytic peptide, hydrolyzed wheat protein, casein Degraded peptides, acylated peptides (palmitoyl oligopeptides, palmitoyl pentapeptides, palmitoyl tetrapeptides, etc.) and the like can be mentioned.

Examples of cell activating components include vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; tannins; flavonoids; saponins; Etc.
Examples of anti-aging components include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, and mevalonolactone.

  Examples of the blood circulation promoting component include plants (e.g., ginseng, ashitaba, arnica, ginkgo, fennel, enmelio, Dutch oak, chamomile, roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake, hawthorn, papaver, Senkyu, assembly, thyme, clove, chimpi, spruce, spruce, spruce, carrot, garlic, butcher bloom, grapes, buttons, maronier, melissa, yuzu, yokuinin, rosemary, rosehip, chimpi, spruce, spruce, peach, apricot , Walnuts, or corn); and glucosyl hesperidin.

Examples of the keratin softening component include salicylic acid, glycolic acid, fruit acid, phytic acid, and sulfur.
Examples of the whitening component include ascorbic acid and its derivatives, arbutin, tocopherol, and tranexamic acid.
Examples of the astringent component include zinc paraphenol sulfonate, zinc oxide, menthol, and ethanol.
Examples of the UV protection component include 2-methoxyhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4,6-tris [4- (2-ethylhexyl) Oxycarbonyl) anilino] -1,3,5-triazine, t-butylmethoxydibenzoylmethane, dibenzylidenedioxoimidazolidinepropionate ethylhexyl, etorhexyltriazoline, paraaminobenzoic acid and its derivatives, paradimethylaminobenzoic acid Examples include octyl, ethylene glycol salicylate, dihydroxybenzophenone, titanium oxide, and zinc oxide.

  Other active ingredients can be used alone or in combination of two or more.

Container The antibacterial composition of the present invention can be used by being housed in a container having a shape and material appropriately selected according to the purpose of use or application. Examples of container shapes include bottle types, tube types, jar types, spoid types, dispenser types, stick types, pouch bags, cheer packs, and the like. Examples of the container material include polyethylene terephthalate, polypropylene, polyethylene (such as HDPE, LDPE, and LLDPE), ABS resin, AS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metal (such as aluminum). In addition, these materials are combined or laminated by performing various coating treatments or mixing these materials, for example, in consideration of strength, flexibility, weather resistance, light shielding properties, component stability, etc. Or it can be used as a container material.

Method of Use The method of using the antibacterial composition of the present invention varies depending on the skin condition, age, sex, etc. of the subject of use, but may be the following method, for example. That is, an appropriate amount (for example, about 0.05 to 5 g) may be applied to the skin several times a day (for example, about 1 to 5 times, preferably 1 to 3 times). Further, the composition is adjusted so that the daily use amount of azelaic acid is, for example, about 0.0001 to 0.5 g, preferably about 0.001 to 0.1 g, more preferably about 0.01 to 0.05 g. What is necessary is just to apply. The application period may be, for example, about 7 to 360 days, preferably about 14 to 180 days.
The subject of use of the antibacterial composition of the present invention is preferably a person who has acne, a product or a pimple on the skin.
The antibacterial composition of the present invention is preferably an antibacterial composition against acne, a product, or a fungus causing a pimple (for example, Propionibacterium acnes or Staphylococcus aureus).

EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these.
(1) Evaluation of solubility of azelaic acid
Using DIGITAL MICROSCOPE VHX-900 (manufactured by KEYENCE), the composition was confirmed at a magnification of 1000 times. The case where no azelaic acid crystals were observed was regarded as a dissolved type, and the case where azelaic acid crystals were observed was regarded as a dispersed type.

(2) Preparation of composition The composition of each example which shows a composition in the following Tables 2-4 was prepared. The component concentration in Tables 2 to 4 is w / v%.

(3) Antibacterial activity test
Propionibacterium acnes
Propionibacterium acnes (ATCC 6919) bacterial solution is inoculated to a GAM agar medium inoculated so that the viable count is about 10 ⁶ CFU / mL, with a sterilized perforation cutter (TOYOBO: Biopsy punch 8 mm, made of stainless steel) 8 mm in diameter Drilled a hole. Each composition was poured into the whole hole (0.1 mL), and after culturing at 37 ° C. for 72 hours, the size of the inhibition circle against the growth of the bacteria was measured.
The results are shown in Tables 2 and 3 above.
In Examples 1 to 6 in which azelaic acid was dissolved and the pH was adjusted to 2 to 6.5, an antibacterial effect was observed. On the other hand, in Comparative Example 1 in which azelaic acid was dispersed and Comparative Example 2 having a pH of 7.0, no antibacterial effect was observed. Moreover, the antibacterial effect was not recognized also in Comparative Examples 3-6 which do not contain azelaic acid.
Moreover, ascorbic acid did not show antibacterial activity, as can be seen from Comparative Examples 4 and 6 in Table 3 showing no antibacterial activity. Nevertheless, the antibacterial activity of Example 4 was stronger than that of Example 3, and the antibacterial activity of Example 6 was stronger than that of Example 5. This shows that ascorbic acid has enhanced the antibacterial activity of azelaic acid.

S.aureus
Staphylococcus aureus (ATCC 6538) bacterial solution inoculated to Mueller Hinton agar medium inoculated to a viable count of about 10 ⁶ CFU / mL with a sterilized perforation cutter (TOYOBO: Biopsy punch 8 mm, stainless steel) An 8mm hole was drilled. Each composition was poured into the whole hole (0.1 mL), cultured at 33 ° C. for 24 hours, and then the size of the inhibition circle for the growth of the bacteria was measured.
The results are also shown in Table 4 above.
In Examples 7 to 9 in which azelaic acid was dissolved and the pH was adjusted to 2 to 6.5, an antibacterial effect was observed. On the other hand, in Comparative Examples 7 to 9 containing no azelaic acid, no antibacterial effect was observed.

The formulation example of the antibacterial composition of the present invention is shown below. The unit of the content of each component is% by weight.
The composition of each of the following formulation examples was observed with DIGITAL MICROSCOPE VHX-900 (manufactured by KEYENCE) at a magnification of 1000, and no azelaic acid crystals were observed.
Formulation Example 1 Lotion Azelaic acid 5.0
Concentrated glycerin 2.0
1,3-butylene glycol 3.0
Polyethylene glycol 10.0
Ethanol 7.0
Hyaluronic acid Na 0.1
Polyoxyethylene hydrogenated castor oil 1.0
Potassium hydroxide appropriate amount
Purified water residue
100.0
The pH was adjusted to 6.4 and filled into a polyethylene terephthalate bottle container.

Formulation Example 2 Cream Azelaic acid 3.0
Concentrated glycerin 5.0
Ethanol 5.0
Carboxy vinyl polymer 0.6
Sodium edetate 0.1
Isopropyl palmitate 5.0
Liquid paraffin 10.0
Seto Macrogol 1.5
Glycerol monostearate2.0
Cetanol 4.0
White petrolatum 4.0
Potassium hydroxide appropriate amount Triethanolamine appropriate amount
Purified water residue
100.0
The pH was adjusted to 5.8 and filled into an HDPE tube container.

Formulation Example 3 Latex Azelaic acid 4.0
1,3-butylene glycol 10.0
Polyethylene glycol 3.0
Propylene glycol 2.0
Xanthan gum 0.3
Isopropyl palmitate 2.0
Liquid paraffin 1.0
Polyoxyethylene hydrogenated castor oil 5.0
White petrolatum 10.0
Potassium hydroxide appropriate amount
Purified water residue
100.0
The pH was adjusted to 6.2 and filled in a polypropylene container.

Formulation Example 4 serum for azelaic acid 2.0
Concentrated glycerin 3.0
1,3-butylene glycol 10.0
Propylene glycol 50.7
Ethanol 3.0
Sodium edetate 0.1
Potassium hydroxide appropriate amount Triethanolamine appropriate amount
Purified water residue
100.0
The pH was adjusted to 5.8 and filled into a polypropylene dispenser container.

Formulation Example 5 Gel Azelaic acid 4.0
1,3-butylene glycol 5.0
Ethanol 10.0
Isopropyl alcohol 3.0
Carboxy vinyl polymer 0.6
Sodium edetate 0.1
Polyoxyethylene hydrogenated castor oil 0.3
Potassium hydroxide appropriate amount
Purified water residue
100.0
The pH was adjusted to 6.4 and filled into a polypropylene jar.

Formulation Example 6 serum liquid Azelaic acid 1.0
L-ascorbic acid 3.0
1,3-butylene glycol 40.0
Diethylene glycol monoethyl ether 20.0
Fragrance 0.1
Potassium hydroxide appropriate amount
Purified water residue
100.0
The pH was adjusted to 3.5 and filled into a glass light-shielding spoid container.

Formulation 7 Serum Azelaic Acid 5.0
L-ascorbic acid 1.0
Propylene glycol 10.0
Diethylene glycol monoethyl ether 60.0
Fragrance 0.1
Potassium hydroxide appropriate amount
Purified water residue
100.0
The pH was adjusted to 4.0 and filled into a glass light-shielding spoid container.

Formulation Example 8 Lotion Azelaic acid 2.0
Ethyl ascorbate 2.0
Glycerin 2.0
Dipropylene glycol 5.0
Ethanol 2.0
Hyaluronic acid Na 0.05
Xanthan gum 0.05
Polyoxyethylene hydrogenated castor oil 1.0
Methyl paraoxybenzoate 0.1
Potassium hydroxide appropriate amount
Purified water residue
100.0
The pH was adjusted to 6.0, filled into a polyethylene terephthalate bottle container, and shrink-wrapped with a polypropylene film.

Formulation Example 9 Cream Azelaic acid 3.0
Ethyl ascorbate 1.0
Glycerin 5.0
Squalane 10.0
Tetra-2-ethylhexanoic acid pentaerythrit 5.0
Polyoxyethylene sorbitan monostearate1.0
Sodium edetate 0.1
(Hydroxyethyl acrylate / acryloyl dimethyltaurine Na) copolymer 4.0
Methyl paraoxybenzoate 0.2
Triethanolamine appropriate amount
Purified water residue
100.0
The pH was adjusted to 6.0 and filled in an EVOH / LDPE laminated tube container.

Formulation Example 10 Latex Azelaic acid 1.0
Ethyl ascorbate 0.5
1,3-butylene glycol 10.0
Polyethylene glycol 3.0
Propylene glycol 2.0
Xanthan gum 0.3
Isopropyl palmitate 2.0
Liquid paraffin 1.0
Polyoxyethylene hydrogenated castor oil 5.0
Methyl paraoxybenzoate 0.2
Potassium hydroxide appropriate amount
Purified water residue
100.0
The pH was adjusted to 6.2 and filled into a polypropylene bottle container.

Formulation Example 11 Gel Azelaic acid 1.0
Ethyl ascorbate 1.5
1,3-butylene glycol 6.0
Glycerin 1.0
Acrylic acid / alkyl methacrylate copolymer 1.2
Methyl paraoxybenzoate 0.2
Sodium hydroxide
Purified water residue
100.0
The pH was adjusted to 5.5 and filled into a polypropylene jar.

Formulation Example 12 Serum Azelaic Acid 5.0
Ethyl ascorbate 1.0
Propylene glycol 10.0
Diethylene glycol monoethyl ether 60.0
Fragrance 0.1
Sodium hydroxide
Purified water residue
100.0
The pH was adjusted to 4.0 and filled into a polypropylene dispenser container.

  The antibacterial composition of the present invention is excellent in antibacterial activity against acne, a product or a causative agent of pimples despite a low azelaic acid concentration, and therefore, as a cosmetic, quasi-drug, or pharmaceutical external preparation. It is useful.

Claims (9)

  An antibacterial composition comprising 0.1 to 10% by weight of dissolved azelaic acid and having a pH of 2 to 6.5.   Furthermore, the composition of Claim 1 containing at least 1 sort (s) chosen from the group which consists of ascorbic acid, its derivative (s), and those salts.   Ascorbic acid, its derivatives, and salts thereof include L-ascorbic acid, L-ascorbic acid phosphate, L-ascorbic acid-2-sulfate, L-ascorbic acid-2-glucoside, ethyl ascorbate and their The composition of claim 2 which is a salt.   The composition of Claim 2 or 3 which contains 0.1-20 weight% of at least 1 sort (s) chosen from the group which consists of ascorbic acid, its derivative (s), and those salts with respect to the whole quantity of a composition.   Furthermore, the composition in any one of Claims 1-4 containing the at least 1 sort (s) of solubilizing agent chosen from the group which consists of a polyhydric alcohol, glycol ether, its derivative (s), and a C1-C4 monohydric alcohol. object.   The dissolution aid is at least one polyhydric alcohol selected from the group consisting of propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, diglycerin, polyethylene glycol, polypropylene glycol, and polyglycerin. Item 6. The composition according to Item 5.   The composition according to claim 5, wherein the solubilizer is ethanol.   The composition according to claim 5, wherein the solubilizer is diethylene glycol monoethyl ether.   The composition according to any one of claims 5 to 8, wherein the dissolution aid is contained in an amount of 1 to 80% by weight based on the total amount of the composition.