JP2005053867A - Dandruff-suppressing composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a dandruff-suppressing composition having effective dandruff-suppressing action, being safe to skin and having good feelings upon use. <P>SOLUTION: This dandruff-suppressing composition and an antimicrobial agent composition for microorganisms of genus Malassezia each comprises an iturin-based peptide represented by formula (1) (wherein R is a 1-6C straight or branched alkyl group) having antibacterial activity as an active ingredient. A cosmetic is prepared by using the dandruff-suppressing composition. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a dandruff suppressing composition and an antibacterial agent composition. More specifically, the present invention relates to an antidandruff composition and an antibacterial composition excellent in effectiveness and safety containing an iturin-based peptide as an active ingredient.

  Dandruff is generally composed of sebaceous gland secretions, sweat gland secretions, epidermal layer exfoliation or detachment, and usually occurs due to increased secretion of sebaceous glands and the like and cell keratinization. Furthermore, it is said that the occurrence of dandruff is pathologically promoted by the propagation of microorganisms that infect the scalp, and in particular, the growth of lipophilic fungi (Malassezia furfur) is greatly involved in the occurrence of dandruff. It is said that. For this reason, hair cosmetics to which antibacterial agents or bactericides are added have been used as hair cosmetics for preventing dandruff.

  However, some of the antibacterial and antibacterial agents used as conventional dandruff prevention and treatment methods have problems with safety to the human body in terms of skin irritation, and the antidandruff effect is sufficient. There was a problem that the skin irritation was caused in some cases when it was not present or when a sufficient amount was added to show the effect. For example, zinc pyrithione (ZPT) is insoluble in water, so that it can be used only in emulsification and dispersion formulations, and it is said that it is desirable to avoid using an amount that can provide sufficient action as much as possible. Yes.

  Iturin-based peptides are known to have fungicidal action against fungi (Mycopathologia, 1994, 127, p. 123-127) (non-patent document 1). It has not been reported that it has bactericidal and antibacterial activity against Malassezia furfur, and its action against dandruff suppression and its application to dandruff suppression components are not known.

Mycopathologia, 1994, vol. 127, p. 123-127

  Accordingly, an object of the present invention is to provide an anti-dandruff composition that has an effective anti-dandruff action, is safe for the scalp and other general skin, and has a good feeling of use.

  In order to achieve the above object, the present inventors have focused on microorganism-derived lipopeptides, which are natural materials excellent in safety. In particular, as a result of extensive research to obtain lipopeptides that can be used effectively on the scalp to effectively prevent dandruff, iturinic peptides have an excellent anti-proliferative effect on the lipophilic fungus Malassezia furfur. The present invention was completed.

  Furthermore, the present invention was completed by finding that combining an iturin-based peptide with a solubilizing agent can sufficiently exhibit the original bactericidal action and reduce skin irritation.

  That is, the present invention relates to the following antidandruff composition, cosmetics using the composition, shampoo, hair tonic, rinse, and antibacterial agent composition.

（式中、Ｒは炭素数が１〜６の直鎖又は分岐状のアルキル基を表わす。）で示されるアイチュリン系ペプチドを有効成分として含有する前項１に記載のフケ抑制組成物。
３．アイチュリン系ペプチドの可溶化剤を含む前項１または２に記載のフケ抑制組成物。
４．可溶化剤が、アルコール類および界面活性剤類の中から選ばれる１種または２種以上である前項３に記載のフケ抑制組成物。
５．可溶化剤が、エタノール、１，３−ブタンジオール、１，２−ペンタンジオール、ジプロピレングリコールおよびサーファクチンナトリウムから選ばれる１種または２種以上である前項４に記載のフケ抑制組成物。
６．アイチュリン系ペプチドを0.005質量％〜2.0質量％含むことを特徴とする前項１乃至５のいずれかに記載のフケ抑制組成物。
７．可溶化剤を0.005質量％〜90.0質量％含む前項６に記載のフケ抑制組成物。
８．前項１乃至７のいずれかに記載のフケ抑制組成物からなる化粧料。
９．前項１乃至７のいずれかに記載のフケ抑制組成物からなるシャンプー。
１０．前項１乃至７のいずれかに記載のフケ抑制組成物からなるヘアトニック。
１１．前項１乃至７のいずれかに記載のフケ抑制組成物からなるリンス。
１２．アイチュリン系ペプチドを含むマラセチア（Malassezia）属微生物用抗菌剤組成物。
１３．式（１）

（式中、Ｒは炭素数が１〜６の直鎖又は分岐状のアルキル基を表わす。）で示されるアイチュリン系ペプチドを有効成分として含有する前項１２に記載の抗菌剤組成物。
１４．アイチュリン系ペプチドの可溶化剤を含む前項１２または１３に記載の抗菌剤組成物。
１５．マラセチア（Malassezia）属微生物が、マラセチア・フルフル（Malassezia furfur）である前項１２乃至１４のいずれかに記載の抗菌剤組成物。 1. An antidandruff composition comprising an iturin-based peptide.
2. Formula (1) with antibacterial activity

The dandruff-suppressing composition according to item 1 above, containing an iturin-based peptide represented by the formula (wherein R represents a linear or branched alkyl group having 1 to 6 carbon atoms) as an active ingredient.
3. 3. The anti-dandruff composition according to item 1 or 2, which contains an iturin-based peptide solubilizer.
4). 4. The antidandruff composition according to item 3 above, wherein the solubilizer is one or more selected from alcohols and surfactants.
5). 5. The antidandruff composition according to item 4, wherein the solubilizer is one or more selected from ethanol, 1,3-butanediol, 1,2-pentanediol, dipropylene glycol and surfactin sodium.
6). The dandruff-suppressing composition according to any one of the preceding items 1 to 5, comprising an iturin type peptide in an amount of 0.005% to 2.0% by mass.
7). The anti-dandruff composition according to item 6 above, containing 0.005% by mass to 90.0% by mass of a solubilizer.
8). A cosmetic comprising the anti-dandruff composition according to any one of 1 to 7 above.
9. A shampoo comprising the anti-dandruff composition according to any one of items 1 to 7.
10. A hair tonic comprising the anti-dandruff composition according to any one of 1 to 7 above.
11. 8. A rinse comprising the anti-dandruff composition according to any one of items 1 to 7.
12 An antibacterial agent composition for microorganisms of the genus Malassezia containing an iturin type peptide.
13. Formula (1)

13. The antibacterial agent composition according to item 12 above, which contains an iturin-based peptide represented by the formula (wherein R represents a linear or branched alkyl group having 1 to 6 carbon atoms) as an active ingredient.
14 14. The antibacterial agent composition according to item 12 or 13 above, which contains an iturin-based peptide solubilizer.
15. 15. The antibacterial agent composition according to any one of items 12 to 14 above, wherein the microorganism of the genus Malassezia is Malassezia furfur.

  The iturin type peptide which is a dandruff suppressing component of the present invention is represented by the following general formula (1).

  The content of the iturin-based peptide in the dandruff-suppressing composition of the present invention is not particularly limited as long as it can be dissolved, but the iturin-based peptide has extremely low solubility in an aqueous system. Therefore, it is desirable to increase the solubility using a solubilizer. A preferred concentration of the iturin type peptide is 0.005 to 2.0% by mass, more preferably 0.01 to 1% by mass, and still more preferably 0.03 to 0.5% by mass.

  The present inventors prepared an aqueous solution of an iturin-based peptide using a solubilizing agent, and measured the minimum growth inhibitory concentration (MIC) for various Malassezia genera using this, and found that it was about 0.01 to 0.03 mass%. I found it. Therefore, when the iturin type peptide in the aqueous solution is 0.03% by mass or more, the effect of the present invention is more remarkably exhibited. However, iturin-based peptides can be used in combination with other bactericides and antibacterial agents, and the concentration of iturin-based peptides can be used at a concentration lower than 0.03% by mass.

  Some iturin peptides have different alkyl chain lengths (R) as shown in formula (1), and the present invention can be carried out with any one of them, but is derived from a microorganism (such as Bacillus). The iturin peptide of the present invention which is a kind of lipopeptide is usually composed of a plurality of components having different R, and the composition referred to in the present invention usually uses a mixture of iturin peptides containing a plurality of Rs. is there.

  The iturin peptide of the present invention can be obtained by using a microorganism (such as Bacillus). For example, “Applied Biochemistry and Biotechnology” is a method of culturing Bacillus microorganisms in a liquid medium containing soybean or its extract as a nitrogen source and accumulating iturin peptides in the culture solution. 1996, 57/58, p. 571-579.

  On the other hand, in the present invention, various alcohol solvents and surfactants can be used as solubilizers. The alcohol may be a monohydric alcohol or a dihydric or higher polyol, and the dihydric alcohol is particularly excellent in terms of solubility. As the surfactant, any of nonionic surfactants, amphoteric surfactants, cationic surfactants, anionic surfactants and the like may be used, and natural surfactants are particularly effective. Here, the natural surfactant refers to a biologically derived surfactant, and includes what is called a so-called natural surfactant and what is called a microbial biosurfactant (Co., Ltd.). (See page 32 of “Special Function Surfactant” issued by CMC.)

  One type of solubilizer may be used, or two or more types may be mixed and used. Furthermore, it is particularly preferable to use a combination of an alcohol solvent and a surfactant because they can be solubilized in a smaller amount than when each is used alone.

  Examples of solubilizers include lower alcohols such as ethanol, phenoxyethanol, isopropanol, butyl alcohol, and benzyl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, oleyl alcohol, behenyl alcohol, and long-chain branched fat. Higher alcohols such as aromatic alcohols, ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, glyceryl monostearate, isoprene glycol, 1,2- Butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butane All, 1,2-pentanediol, 1,5-pentanediol, 2,3-pentanediol, 2,4-pentanediol, sorbitol, malbitol, raffinose, hexylene glycol, lauric acid diethanolamide, fatty acid diethanolamide, etc. Polyol, polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether (APE), polyoxyethylene alkyl ether, polyoxyethylene alcohol alcohol ether, polyoxyethylene polyhydric alcohol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyvalent Nonionic surfactants such as alcohol fatty acid esters, ethylene glycol fatty acid esters, polyglycerin fatty acid esters, and sucrose fatty acid esters, and tetraalkylammonium salts Ionic surfactant, alkyl trimethyl ammonium salt, alkyl pyridinium chloride, stearyl trimethyl ammonium chloride, fatty acid salt, alkyl sulfate (AS), alkyl ether sulfate ester salt (AES), alkyl sulfate triethanolamine, sodium polyoxyethylene lauryl sulfate Anionic surfactants such as sodium lauryl sulfate (LAS) and sodium lauroyl glutamate, betaine types such as betaine lauryl dimethylaminoacetate, amphoteric surfactants such as sulfobetaine type and sulfoamino acid type, polyether modified silicone, amino modified Examples include silicone surfactants such as silicone, and natural surfactants such as lecithin, lysophosphatidylcholine, ceramide, cerebroside, and surfactin sodium. One or two or more of these can be appropriately selected and blended.

  The blending amount of the solubilizing agent in the dandruff suppressing composition of the present invention is appropriately selected depending on stability, safety, etc. depending on the purpose of use, and is not particularly limited, but is the minimum necessary for sufficiently solubilizing the iturin-based peptide component. Limited amount is required. That is, it varies depending on the amount of iturin-based peptide used and the type of solubilizing agent, but the solubilizing agent is preferably used in an amount of 0.005 to 90% by mass, more preferably 0.5 to 80% by mass, and still more preferably 1.0 to 70% by mass. is there.

  To illustrate the amount of solubilizer used, it is possible to solubilize at 0.7% by mass or more when 1,3-butanediol or 1,2-pentanediol is used alone in order to incorporate 0.1% by mass of iturin-based peptide. . Furthermore, when surfactants such as surfactin sodium and sodium lauroyl glutamate are used alone, they can be solubilized at 0.1% by mass or more. When alcohols and surfactants are used in combination, each amount can be solubilized in a smaller amount than that used alone. For example, in order to solubilize 0.1% by mass of iturin-based peptide, 0.05% by mass of surfactin sodium and 0.5% by mass of 1,2-pentanediol may be used. In order to express the effects of the present invention more remarkably, the solubilizing agent is an interface between alcohols such as 1,3-butanediol, 1,2-pentanediol, dipropylene glycol, ethanol and surfactin sodium. It is preferred to combine with an active agent.

  In addition, as a method of solubilizing the iturin-based peptide component using a solubilizer, for example, it is possible to add the iturin-based peptide component to the solubilizer and, if necessary, add water and the like, and stir. More preferably, it is better to heat and stir using ultrasonic waves. Furthermore, it can be easily solubilized by high temperature and pressure (120 ° C., 5 to 20 minutes) using an autoclave or a pressure vessel.

  The composition of the present invention can be prepared by blending an iturin-based peptide component, which is an essential component, and a solubilizing agent according to a conventional method. Moreover, various components used in order to make agents for hair cosmetics, hair nourishing agents, hair styling agents and the like can be added as necessary within the range not impairing the effects of the present invention. Examples of such components include tar pigments, colored pigments such as iron oxide, antiseptic components such as parabens, film forming agents such as dimethylpolysiloxane and methylphenylpolysiloxane, silicone oils such as cyclic silicones, paraffin, liquid paraffin And the like. Emollients include, for example, hydrocarbons such as petrolatum, olefin oligomers, squalane, olive squalane, rice squalane, rice germ oil, jojoba oil, castor oil, safflower oil, olive oil, macadamia nut oil, sunflower oil and other vegetable oils, beeswax, molasses , Waxes such as carnauba wax, ester oils such as octyldodecyl myristate, cetyl palmitate, isostearyl isostearate and isopropyl myristate, sterols such as cholesterol, phytosterols, branched fatty acid cholesterol esters, macadamia nut fatty acid phytosteryl esters and derivatives thereof , Processing oils such as hardened oil, stearic acid, myristic acid, isostearic acid, oleic acid, iso-type long chain fatty acids, higher fatty acids such as anteiso-type long chain fatty acids, limonene, Terpenes such as iodized bisabolol, caprylic-capric acid glyceryl, 2-ethylhexanoic acid glyceryl, triiso-type long chain fatty acid glyceryl, and triglycerides such as tripalmitate glyceryl. Sodium citrate, potassium acetate, sodium succinate used for pigments such as titanium oxide and zinc oxide, antioxidants such as dibutylhydroxytoluene, inorganic salts such as sodium chloride, magnesium chloride, sodium sulfate, potassium nitrate, and buffering agents , Organic acid salts such as sodium aspartate, sodium lactate, sodium cocoyl methyl taurine, salts such as ethanolamine hydrochloride, ammonium nitrate, distearyldimethylammonium chloride, arginine hydrochloride, chelating agents such as edetic acid, xanthan gum, carboxyvinyl polymer, carrageenan , Pectin, alkyl-modified carboxyvinyl polymer, thickener such as agar, neutralizer such as potassium hydroxide, diisopropanolamine, lauryldimethylaminooxide, triethanolamine, hyal Phosphate, biopolymers such as collagen, an ultraviolet absorber such as hydroxy methoxy benzophenone sulfonic acid salt can be exemplified.

The dandruff-suppressing composition of the present invention has any dosage form, for example, hair cosmetics such as shampoos and rinses, hair tonics such as hair tonics, hair conditioners, and scalp treatments, and hair styling such as hair liquids, hair sprays, and hair creams. The dosage form can be taken.
When these dosage forms are used, a general blending component is added and adjusted according to each dosage form. For example, in a shampoo, a general surfactant is added in addition to water and a solubilizer. In hair tonics, a greater amount of ethanol is added than for use as a solubilizer. In rinsing, it is common to add a polyol, a higher alcohol, or a higher fatty acid alcohol ether in addition to water.

  The dandruff suppressing composition of the present invention is safe and can effectively prevent the occurrence of dandruff.

  EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, this invention is not limited by this.

Example 1 Production of Iturin Peptide Using Fermentor Bacillus subtilis SD142 was streaked on L plate medium and grown overnight at 35 ° C., then 1 was added to a flask with baffle to which 50 mL of L medium was added. Inoculated with platinum ears and cultured at 35 ° C. and 150 rpm for 8 hours. A medium of the following composition I was prepared in a 5 L fermentor, inoculated with a culture medium of L medium, and cultured at 35 ° C. for 150 hours while adjusting the pH to 6.5 to 7.5 with 20% aqueous ammonia.

[Composition I]
160g soy flour
MgSO ₄・ 7H ₂ O 5g
0.25g of FeSO ₄ · 7H ₂ O
MnSO ₄ · 5H ₂ O 0.22g
CaCl ₂ 1.84 g
Minamata 450g
Ion exchange water 1383g

  The iturin peptide contained in the supernatant obtained by centrifuging the culture solution was quantified by HPLC under the following conditions. As a result, 3.8 g / L of iturin type peptide was produced. The HPLC diagram and peak area fraction of the produced iturin peptide are shown in FIG.

[Analysis conditions]
Sample volume: 10 μL,
Column: Shodex C18P4E (manufactured by Showa Denko KK),
Column temperature: 40 ° C
Eluent: acetonitrile / 10 mM ammonium acetate aqueous solution = 35/75 (V / V),
Flow rate: 1.5 mL / min,
Detector: UV detector (wavelength: 205 nm).
* Quantification was determined by summing up the peaks of all iturin-based peptide compositions based on a calibration curve prepared using Iturin A (Sigma Aldrich) as a standard.

Example 2: Growth inhibition test against lipophilic fungus Malassezia furfur After dissolving an iturin-based peptide in ethanol / water (= 80/20) to 2% by mass, potato dextrose (PDA) medium (DIFCO) Sensitive plates were prepared by adding from a maximum of 1000 ppm to 1/2 dilution series. At this time, the concentration of 1,3-butanediol was adjusted to 4% by mass. Each plate was inoculated with the lipophilic fungus Malassezia furfur using a platinum loop and cultured at 25 ° C. for 7 days. Furthermore, as a result of preparing and inoculating the sensitive plates of miconazole nitrate, zinc pyrithione, and piroctone olamine, which are conventionally used antidandruff agents, and comparing them, it was found that iturin peptides were superior to these. (Table 1).

Example 3: Effect on sensitivity by solubilizing agent When iturin-based peptide was dissolved with 1,3-butanediol, 1,2-pentanediol, sodium lauroylglutamate, or surfactin sodium instead of ethanol of Example 1 Table 2 shows the results of examining the change in sensitivity. As a result, it was found that changing the solubilizing agent had no effect on the growth inhibiting ability.

Example 4: Stabilization by solubilizing agent Since iturin peptides aggregate and aggregate in an aqueous solution due to a high temperature range (40 ° C or higher) or temperature change, the solubilizing agent of the present invention prevents aggregation and precipitation. Stability can be increased. Table 3 shows the results of examining the storage stability for 1 month at 50 ° C. with different solubilizers. Water (pH 7.0 → 1.0% by mass or more dissolves when the pH is high alkali. If left as it is, the amino acid side chain is modified. For example, glutamine changes to glutamic acid, so that polar residues increase and solubilize. However, in this case, the antibacterial activity is lost.) When 0.01% by mass of iturin type peptide is dissolved using only this, precipitation occurs at 50 ° C. for 1 day. As a result, it has been found that the dissolution stability is dramatically increased by the combination of the solubilizers of the present invention.

Example 5: Shampoo 1

[Preparation method]
It was prepared by adding 5.0% by mass of iturin-based peptide to the 40% by mass aqueous solution of (4), solubilizing with an autoclave (120 ° C., 20 minutes) and then adding to an aqueous solution containing other components.

Example 6: Shampoo 2

[Preparation method]
It was prepared by adding 0.7% by mass of iturin-based peptide to the 35% by mass aqueous solution of (5) and solubilizing by an autoclave (120 ° C., 20 minutes), and then adding it to an aqueous solution containing other components.

Example 7: Hair tonic 1

[Preparation method]
In (4), a solution in which the iturin-based peptide was dissolved at room temperature to prepare 1.05% by mass was prepared and mixed with other components.

Example 8: Hair tonic 2

[Preparation method]
A predetermined amount of iturin-based peptide was added to an aqueous solution mixed with components other than iturin-based peptide and dissolved at room temperature to prepare.

Example 9: Rinse 1

[Preparation method]
0.43% by mass of iturin-based peptide was added to an aqueous solution containing (2), (3) and (5) and solubilized while warming (80 ° C.), and then the remaining components were mixed to prepare.

Example 10: Rinse 2

[Preparation method]
1.0 mass% of iturin-based peptide was added to the 60 mass% aqueous solution of (3) and dissolved by autoclave (120 ° C., 10 minutes). This was added to an aqueous solution to which other components were added to prepare a predetermined concentration.

The HPLC figure of the iturin type peptide produced in Example 1 and its peak area fraction are shown.

Claims (15)

  An antidandruff composition comprising an iturin-based peptide. Formula (1) with antibacterial activity

The dandruff-suppressing composition according to claim 1, comprising an iturin-based peptide represented by the formula (wherein R represents a linear or branched alkyl group having 1 to 6 carbon atoms) as an active ingredient.   The anti-dandruff composition according to claim 1, comprising a solubilizing agent for iturin-based peptides.   The dandruff-suppressing composition according to claim 3, wherein the solubilizer is one or more selected from alcohols and surfactants.   The dandruff suppressing composition according to claim 4, wherein the solubilizer is one or more selected from ethanol, 1,3-butanediol, 1,2-pentanediol, dipropylene glycol and surfactin sodium.   The antidandruff composition according to any one of claims 1 to 5, comprising an iturin type peptide in an amount of 0.005% by mass to 2.0% by mass.   The anti-dandruff composition according to claim 6, comprising 0.005% by mass to 90.0% by mass of a solubilizer.   A cosmetic comprising the dandruff suppressing composition according to any one of claims 1 to 7.   A shampoo comprising the anti-dandruff composition according to any one of claims 1 to 7.   A hair tonic comprising the anti-dandruff composition according to any one of claims 1 to 7.   A rinse comprising the anti-dandruff composition according to any one of claims 1 to 7.   An antibacterial agent composition for microorganisms of the genus Malassezia containing an iturin type peptide. Formula (1)

The antibacterial composition according to claim 12, comprising an iturin-based peptide represented by the formula (wherein R represents a linear or branched alkyl group having 1 to 6 carbon atoms) as an active ingredient.   The antibacterial agent composition according to claim 12 or 13, comprising a solubilizing agent for iturin-based peptides.   The antibacterial composition according to any one of claims 12 to 14, wherein the microorganism of the genus Malassezia is Malassezia furfur.

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