Composition for improving resident flora of scalp, haircare product, and therapeutic agent for scalp seborrheic dermatitis

Abstract

The present invention addresses the problem of providing a new compound capable of improving the resident flora of a scalp.　This problem can be solved by means of a composition for improving the resident flora of a scalp, said composition containing, as an active ingredient, a peptide composed of L-lysine and L-arginine.

Description

Composition for improving resident flora of scalp, hair care product and therapeutic agent for seborrheic dermatitis of scalp

[0001] The disclosure in the present application relates to a composition for improving the resident flora of the scalp, a hair care product containing the composition for improving the resident flora of the scalp, and a therapeutic agent for seborrheic dermatitis of the scalp.

[0002] On the surface of healthy skin, similar to the intestinal tract system, various types of bacteria (hereinafter sometimes referred to as "resident flora") are present. The scalp is a part of the skin and is covered with hair, so secreted sebum, sweat and the like are easily utilized by the resident flora, providing a comfortable propagation environment. Staphylococcus epidermidis, which is one of the resident flora, decomposes triglycerides as sebum components into fatty acids and glycerin. Fatty acids keep the skin weakly acidic and serve to prevent the proliferation of pathogenic Staphylococcus aureus that prefers an alkaline environment, and glycerin exerts a moisturizing effect on the scalp and can maintain the scalp barrier function. Therefore, Staphylococcus epidermidis is recognized as a beneficial good bacterium for the scalp. On the other hand, when the skin is injured or the skin becomes alkaline, Staphylococcus aureus proliferates in large quantities, the pH environment of the skin is destroyed, and Staphylococcus epidermidis decreases sharply, causing inflammation, abscesses and the like. Malassezia furfur, which is a fungus and one of the resident flora, decomposes triglycerides as sebum components into saturated fatty acids and unsaturated fatty acids, and the unsaturated fatty acids impart irritation to the scalp, causing scalp inflammation, dandruff, itchiness and the like. In addition, the sebaceous glands of the scalp are the most widely distributed throughout the whole body, and the distribution of sweat glands is the second most after the hands and feet. Therefore, compared with the skin of other parts, the scalp secretes more sebum and sweat, and the balance of the resident flora is more likely to be disrupted. Even minor changes occurring in the body such as exercise, ultraviolet rays, emotions and stress may disrupt the balance of the resident flora.

[0003] Patent Document 1 discloses that magnesium lactate and / or calcium lactate reduces the number of Staphylococcus aureus while suppressing the decrease in the number of Staphylococcus epidermidis in the resident flora of the skin.

[0004] JP 2018-52891 A

[0005] However, it is unclear whether the invention described in Patent Document 1 above can reduce the number of Malassezia furfur bacteria. Furthermore, bacteria utilize various survival signals to ensure their own survival. Therefore, even if compounds that can reduce the number of Staphylococcus aureus bacteria while suppressing the decrease in the number of Staphylococcus epidermidis bacteria are known, the search for new compounds that can improve the balance of the normal flora of the scalp is desirable.

[0006] The disclosures in this application are made to solve the above-mentioned problems. Through diligent research, the inventors have newly discovered that a peptide consisting of L-lysine and L-arginine can improve the balance of the resident microbiota of the scalp.

[0007] The disclosures in this application relate to a composition for improving the resident microbiota of the scalp, a hair care product containing the resident microbiota-improving composition, and a treatment agent for seborrheic dermatitis of the scalp, as described below.

[0008] (1) A composition for improving the resident microbiota of the scalp, comprising a peptide consisting of L-lysine and L-arginine as an active ingredient. (2) The composition for improving the resident microbiota of the scalp according to (1), which suppresses the growth of at least one selected from the group consisting of Malassezia furfur, Staphylococcus aureus, and Staphylococcus capitis. (3) The composition for improving the resident microbiota of the scalp according to (1), which promotes the growth of Staphylococcus epidermidis. (4) The composition for improving the resident microbiota of the scalp according to (1), which suppresses the growth of Malassezia furfur, Staphylococcus aureus, and Staphylococcus capitis, and promotes the growth of Staphylococcus epidermidis. (5) The composition for improving the resident microbiota of the scalp according to (2), wherein the content of the peptide is 0.008% by mass or more. (6) The scalp microbiota improvement composition according to (3) above, wherein the peptide content is 0.008% by mass or more. (7) The scalp microbiota improvement composition according to (4) above, wherein the peptide content is 0.08% by mass or more. (8) The scalp microbiota improvement composition according to any one of (1) to (7) above, further comprising maltooligosaccharides. (9) The scalp microbiota improvement composition according to (8) above, wherein the maltooligosaccharide is at least one selected from the group consisting of maltotriose, maltotetraose, and maltopentaose. (10) The scalp microbiota improvement composition according to (9) above, wherein the maltooligosaccharide is maltotetraose. (11) A hair care product comprising the scalp microbiota improvement composition according to any one of (1) to (10) above. (12) The hair care product according to (11) above, wherein the hair care product is selected from the group consisting of hair shampoo, hair conditioner, hair treatment, hair mask, scalp cleanser, scalp essence, hair tonic, and hair lotion. (13) A composition for improving the resident microbiota of the scalp according to any one of (1) to (10) above, which has a therapeutic effect on seborrheic dermatitis of the scalp. (14) A therapeutic agent for seborrheic dermatitis of the scalp, comprising a peptide consisting of L-lysine and L-arginine as an active ingredient.

[0009] The scalp microbiome improving composition disclosed in this application can improve the scalp microbiome.

[0010] Figure 1 is a graph showing the results of bacterial growth when Peptiskin was added to the culture medium in Example 1. Figure 2 is a graph showing the results of bacterial growth when polylysine was added to the culture medium in Comparative Example 1. Figure 3 is a graph showing the results of bacterial growth when succinic acid was added to the culture medium in Comparative Example 2. Figure 4 is a graph showing the results of bacterial growth when ferulic acid was added to the culture medium in Comparative Example 3. Figure 5 is a graph showing the results of bacterial growth when Peptiskin and L-MT were added to the culture medium in Example 2. Figure 6 is a graph showing the results of bacterial growth when Peptiskin was added to the culture medium in Example 3.

[0011] The following provides a detailed description of a composition for improving the natural microbiome of the scalp (hereinafter sometimes simply referred to as "the composition"), a hair care product containing the composition, and a treatment for seborrheic dermatitis of the scalp.

[0012] In this specification, a numerical range indicated by "~" means a range that includes the numbers before and after "~" as the lower and upper limits. Numbers, numerical ranges, and qualitative expressions (e.g., expressions such as "identical" or "abbreviated") shall be interpreted as indicating numbers, numerical ranges, and properties that include errors generally accepted in the art.

[0013] <Embodiments of the Composition> The composition according to the embodiment contains a peptide consisting of L-lysine and L-arginine (hereinafter sometimes simply referred to as "peptide") as an active ingredient. The peptide is not particularly limited as long as it is a peptide in which L-lysine and L-arginine are linked by an amide bond. The peptide can be produced, for example, by enzymatic synthesis of L-lysine and L-arginine. Alternatively, commercially available products may be used. Examples of commercially available products, though not limited to them, include Peptiskin (PEPTISKIN®, Nikko Chemicals Co., Ltd.), EPITENSIVE EVO (LipoTrue, S.L.), Frag-Brillin retained® (LipoTrue, S.L.), etc.

[0014] The composition according to the embodiment is provided by dissolving the above-described peptide in a solvent. The solvent is not particularly limited as long as it is a medium that dissolves the peptide. Examples of solvents, though not limited to them, include water, brine, and deionized water.

[0015] The composition according to the embodiment has the following effects: (1) It inhibits the growth of Malassezia furfur and / or Staphylococcus aureus (hereinafter sometimes referred to as "harmful bacteria"). (2) It promotes the growth of Staphylococcus epidermidis (hereinafter sometimes referred to as "beneficial bacteria"). (3) It inhibits the growth of Malassezia furfur and Staphylococcus aureus, and promotes the growth of Staphylococcus epidermidis.

[0016] The peptide content in the composition is not particularly limited as long as it is within the range that produces the effects described in (1) to (3) above. Although not limited, as a guideline for (1) and (2) above, the peptide content in the composition should be 0.008% by mass or more, and as a guideline for (3) above, the peptide content in the composition should be 0.08% by mass or more. The above values ​​are guidelines, and the actual peptide content may be smaller or larger than the above values.

[0017] Furthermore, the composition according to the embodiment may optionally contain other components (hereinafter sometimes referred to as "optional additional component 1"), as long as they are within the range of achieving the effects described above. Examples of optional additional component 1 include the following components.

[0018] (1) Maltooligosaccharides. Maltooligosaccharides are not limited to these, but preferred examples include maltotriose, maltotetraose, maltopentaose, etc., with maltotetraose being more preferred. (2) Zinc L-pyrrolidone carboxylate, and / or hinokitiol. (3) Oily raw materials. For example, hydrocarbon oils, esters, natural oils and synthetic oils, higher alcohol oils, fatty acid oils, waxy oils, silicone oils or their derivatives, phytosterol derivatives, protein derivatives, lanolin, lanolin derivatives, lecithin and other oily bases, essential oils, fragrances or cooling agents, UV absorbers, etc. (4) Water-soluble raw materials. For example, polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, and polyethylene glycol; lower alcohols such as ethanol; pH adjusters and buffers such as citric acid, sodium citrate, lactic acid, and sodium hydroxide; sugars such as sucrose, trehalose, xylitol, and oligosaccharides; inorganic salts such as sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, sodium carbonate, anhydrous sodium carbonate, and magnesium sulfate; stabilizers such as sodium metaphosphate, ethylenediaminetetraacetic acid, and disodium ethylenediaminetetraacetic acid (sodium edetate); and antioxidants such as dibutylhydroxytoluene (BHT) and ascorbic acid. (5) Preservatives, pigments, powders, blood circulation promoters, natural extracts derived from plants and animals, flavonoids such as anthocyanins and their derivatives, vitamins and their derivatives, amino acids, photosensitizers, preservatives, cooling agents or aromatics such as menthol, peppermint water, rose water, water-swellable clay minerals and various powders, ultraviolet scattering agents, pigments, etc.

[0019] When adding the optional additional component 1 mentioned above, you may choose one type or add two or more types in combination.

[0020] Malassezia furfur, one of the commensal microbiota of the scalp, is a fungus that causes seborrheic dermatitis, and it is known that seborrheic dermatitis can be prevented, alleviated, or treated with compositions exhibiting antifungal activity (see Japanese Patent Publication No. 2002-140631). The composition according to the embodiment can be used as a therapeutic agent for scalp seborrheic dermatitis because it suppresses the proliferation of Malassezia furfur, as shown in the examples described later.

[0021] <Embodiment of the Treatment Agent for Seborrheic Dermatitis of the Scalp> Next, the treatment agent for seborrheic dermatitis of the scalp according to the embodiment will be described. The treatment agent for seborrheic dermatitis of the scalp according to the embodiment contains a peptide consisting of L-lysine and L-arginine as an active ingredient. As described above, the composition according to the embodiment can be used as a treatment agent for seborrheic dermatitis of the scalp. Therefore, if "composition" according to the embodiment described above is read as "treatment agent for seborrheic dermatitis of the scalp," the description of the composition according to the embodiment becomes the description of the treatment agent for seborrheic dermatitis of the scalp according to the embodiment. Therefore, to avoid duplication, the description of the treatment agent for seborrheic dermatitis of the scalp according to the embodiment will be omitted.

[0022] <Embodiments of Hair Care Products> Next, a hair care product according to the embodiment will be described. The hair care product includes any of the compositions according to the embodiment. The hair care product is not particularly limited as long as it includes the compositions according to the embodiment, but examples include hair shampoo, hair conditioner, hair treatment, hair mask, scalp cleanser, scalp essence, hair tonic, hair lotion, etc.

[0023] Hair care products may optionally contain other ingredients (hereinafter sometimes referred to as "optional additional ingredients 2") in addition to the above-described composition. Examples of optional additional ingredients 2 include surfactants, cationic polymers, chelating agents, preservatives, fragrances, pH adjusters, and ion-exchanged water.

[0024] The composition according to the embodiment may contain, as optional additional component 1, any of the following: a chelating agent, a preservative, a fragrance, or a pH adjuster. In that case, the optional additional component already added to the composition according to the embodiment does not need to be added as optional additional component 2 when manufacturing the hair care product according to the embodiment, or the same or a different type of component may be added.

[0025] Examples of surfactants, though not limited to them, include coconut fatty acid alanine salt, alkyl sulfonate, coconut fatty acid taurine salt, coconut fatty acid taurine taurine salt, alkylamide betaine type amphoteric surfactants, and amide sulfobetaine type amphoteric surfactants. The surfactant may be one type or may contain two or more types.

[0026] Examples of coconut fatty acid alanine salts, though not limited to them, include sodium cocoyl alanine, sodium lauroyl alanine, and sodium lauroyl methyl alanine. Examples of alkyl sulfonates, though not limited to them, include sodium olefin (C14-16) sulfonate.

[0027] Examples of coconut fatty acid taurine salts include, but are not limited to, sodium cocoyl methyl taurate and sodium cocoyl methyl taurate. Examples of coconut oil fatty acid taurine salts include, but are not limited to, sodium cocoyl methyl taurate. Examples of alkylamide betaine type amphoteric surfactants include, but are not limited to, cocamidopropyl betaine. Examples of amide sulfobetaine type amphoteric surfactants include, but are not limited to, cocamidopropyl hydroxysultaine and lauryl hydroxysultaine.

[0028] Examples of cationic polymers, though not limited to them, include polyquaternium-7, polyquaternium-10, polyquaternium-11, polyquaternium-67, guar hydroxypropyltrimonium chloride, and hydroxypropyltrimonium chloride starch. It is sufficient to include one or more cationic polymers.

[0029] Chelating agents are not limited to those listed, but examples include disodium EDTA. Preservatives are not limited to those listed, but examples include sodium benzoate and phenoxyethanol. pH adjusters are not limited to those listed, but examples include citric acid.

[0030] When adding the optional additional component 2 mentioned above, you may choose one type or add two or more types in combination.

[0031] Examples are provided below to specifically illustrate the embodiments disclosed in this application. These examples are solely for illustrative purposes and are not intended to limit or restrict the scope of the invention disclosed in this application.

[0032] (1) The types of reagents used in the reagent examples and their suppliers are as follows: ・Succinic acid: Anhui Huaheng Biotechnology Co., Ltd. ・Ferulic acid: Tsukuno Foods Co., Ltd. ・Polylysine: Ichimaru Falcos Co., Ltd. ・Peptide: Peptiskin, Nikko Chemicals Co., Ltd. ・Maltotetraose-containing oligosaccharide: Leoguard MT, Lion Specialty Chemicals Co., Ltd.

[0033] (2) The three types of commensal bacteria on the scalp used in the bacterial example are as follows. The three types of bacteria were provided by the National Institute of Technology and Evaluation Biotechnology Center (NBRC). ・Staphylococcus aureus: NBRC12732 ・Malassezia furfur: NBRC0656 ・Staphylococcus epidermidis: NBRC12993

[0034] (3) The culture medium and cultured Staphylococcus aureus and Staphylococcus epidermidis were cultured aerobically at 37°C using NBRC802 medium (1% hypopeptone, 0.2% yeast extract, 0.1% magnesium sulfate heptahydrate). Malassezia furfur was cultured aerobically at 37°C using YM medium (1% glucose, 0.5% peptone, 0.3% yeast extract, 0.3% malt extract) to which olive oil was added to a final concentration of 1.0%.

[0035] (4) Bacterial Growth Test The inhibitory or promoting effect on bacterial growth when each reagent was added was quantified using the following procedure. 200 μl of culture medium (180 μl of each bacterial solution, 20 μl of reagent or sterile water) was added to each well of a 96-well plate, and incubated at 37°C using a Maximizer M BR-022UP (Taitec). In the case of Malassezia furfur, the procedure was the same except that olive oil was added to a final concentration of 0.1%. The turbidity of the culture medium was measured at a wavelength of 600 nm at time intervals (0, 12, 24 hours) using an Infinite 200Pro MPlex (Tecan Japan Co., Ltd.). The growth of each bacterium was evaluated by calculating the mean and standard deviation.

[0036] (5) Statistical analysis: After one-way analysis of variance (ANOVA), a significance test was performed using the Dunnett method between the turbidity of the control group and the turbidity of samples treated with different concentrations at the same time. The significance level was set at 5%. EZR was used for statistical analysis.

[0037] <Example 1> Peptiskin was used as the reagent. Peptiskin was added to the culture medium so that the concentrations in the medium were 0% by mass, 0.02% by mass, 0.20% by mass, and 2.00% by mass. Bacteria were grown according to the procedure described in "(4) Bacterial Growth Test" above, and the analysis was performed according to "(5) Statistical Analysis" above. The results are shown in Figure 1. The three graphs for each concentration show the results at 0 hours after the start of culture on the left, 12 hours after the start of culture in the center, and 24 hours after the start of culture on the right. The same applies to Figures 2 to 5. The proportion of peptide contained in Peptiskin is 40%. Therefore, the value obtained by multiplying the Peptiskin (%) value on the horizontal axis of Figure 1 by 0.4 is the proportion of peptide used in Example 1. The same applies to Example 2 and Figure 5, which will be described later.

[0038] <Comparative Examples 1-3> In Comparative Examples 1-3, experiments were conducted using reagents known to have antibacterial and antifungal activity. More specifically, the experiments were conducted in the same procedure as in Example 1, except that polylysine (Comparative Example 1: concentrations of 0%, 0.002%, 0.020%, and 0.200%), succinic acid (Comparative Example 2: concentrations of 0 mM, 0.10 mM, 1.00 mM, and 10.00 mM), and ferulic acid (Comparative Example 3: concentrations of 0 mM, 0.01 mM, 0.10 mM, and 1.00 mM) were used as reagents. Figure 2 shows the results for Comparative Example 1, Figure 3 shows the results for Comparative Example 2, and Figure 4 shows the results for Comparative Example 3.

[0039] As shown in Figure 1, when Peptiskin was added to the culture medium, the growth of Malassezia furfur and Staphylococcus aureus was significantly suppressed, and the growth of Staphylococcus epidermidis was significantly increased. On the other hand, the following results were obtained in Comparative Examples 1 to 3: As shown in Figure 2, when polylysine (Comparative Example 1) was used, the growth of Staphylococcus epidermidis, a beneficial bacterium, was suppressed. As shown in Figure 3, when succinic acid (Comparative Example 2) was used, at a concentration that significantly suppressed the growth of Staphylococcus aureus, a harmful bacterium, the growth of Staphylococcus epidermidis, a beneficial bacterium, was also suppressed. As shown in Figure 4, when ferulic acid (Comparative Example 3) was used, the growth of Malassezia furfur was significantly suppressed after 24 hours, but it did not affect the growth of Staphylococcus epidermidis and Staphylococcus aureus.

[0040] From these results, we confirmed that peptides composed of L-lysine and L-arginine exhibit remarkable effects, such as suppressing the growth of harmful bacteria and promoting the growth of beneficial bacteria. In particular, while the polylysine in Comparative Example 1 was composed only of L-lysine, using a peptide composed of both L-lysine and L-arginine yielded effects that could not be expected from a peptide composed only of L-lysine.

[0041] Figure 1 shows that when the Peptiskin concentration was 0.02% by mass or higher (peptide concentration of 0.008% by mass or higher), the growth of Staphylococcus aureus was suppressed and the growth of Staphylococcus epidermidis was promoted. It also shows that when the Peptiskin concentration was 0.2% by mass or higher (peptide concentration of 0.08% by mass or higher), the growth of Malassezia furfur and Staphylococcus aureus was suppressed, and the growth of Staphylococcus epidermidis was promoted. However, these concentrations were determined for experimental purposes, and the lower and upper limits of the concentration can be determined as appropriate. The effect of Peptiskin in improving the balance of the normal flora of the scalp was discovered for the first time in this application. When adding Peptiskin to a product, it can be set as appropriate within the range that exhibits the effects disclosed in this application or a range that exhibits some of the effects.

[0042] <Example 2> The experiment was carried out in the same procedure as in Example 1, except that Peptiskin and maltotetraose-containing oligosaccharide (L-MT) were used as reagents and the concentrations were as shown below. The results are shown in Figure 5.

[0043] As shown in Figure 1B, when Staphylococcus epidermidis was cultured for 24 hours in a medium supplemented with 2.00% by mass of Peptiskin (peptide concentration of 0.8% by mass), there was no significant difference in bacterial growth compared to the control group. On the other hand, as is clear from Figure 5, when Staphylococcus epidermidis was cultured for 24 hours in a medium mixed with 2.0% by mass of Peptiskin (peptide concentration of 0.8% by mass) and 2.0% by mass of L-MT, it was confirmed that bacterial growth was significantly promoted compared to the control group. From the results of Examples 1 and 2, it was confirmed that Peptiskin alone produces the effects disclosed in this application, but the effect is enhanced when used in combination with L-MT.

[0044] <Example 3> Next, the effect of Peptiskin on Staphylococcus capitis, one of the resident flora of the scalp, was investigated. S. capitis is a bacterium that resides on sebum-rich skin such as the scalp, and normally contributes to maintaining the homeostasis of the resident flora as a symbiotic bacterium. On the other hand, it can cause opportunistic infections in immunocompromised states or in the presence of medical devices. Therefore, similar to Staphylococcus aureus, it is considered preferable that its proliferation is suppressed. The specific procedure is as follows.

[0045] (1) Source of Bacteria The bacteria were provided by the National Institute of Technology and Evaluation Biotechnology Center (NBRC). ・S. capitis: NBRC 115779

[0046] (2) Medium and Culture S. capitis was aerobically cultured at 37°C using NBRC 802 medium (1% hipopeptone, 0.2% yeast extract, 0.1% magnesium sulfate heptahydrate).

[0047] The same Peptiskin as in Example 1 was used as the reagent. Peptiskin was added to the medium so that the concentrations in the medium were 0% by mass (Blank), 0.002% by mass, 0.02% by mass, 0.2% by mass, and 2.0% by mass, the bacteria were proliferated according to the procedure described in the above "(4) Bacterial Proliferation Test", and the analysis was performed according to the above "(5) Statistical Analysis". The results are shown in Figure 6. The three graphs for each concentration show the results at 0 hours after the start of culture on the left, 12 hours after the start of culture in the center, and 24 hours after the start of culture on the right. As is clear from Figure 6, it was confirmed that the proliferation of S. capitis can be suppressed by adding Peptiskin to the medium.

[0048] The composition disclosed in the present application can improve the balance of the resident flora of the scalp. Therefore, it is useful in the pharmaceutical industry and the cosmetic industry.

Claims

1. A composition for improving the resident microbiota of the scalp, containing a peptide consisting of L-lysine and L-arginine as an active ingredient.

2. The scalp microbiota improving composition according to claim 1, which suppresses the growth of at least one selected from the group consisting of Malassezia furfur, Staphylococcus aureus, and Staphylococcus capitis.

3. The scalp microbiome improving composition according to claim 1, which promotes the growth of Staphylococcus epidermidis.

4. The scalp microbiota improving composition according to claim 1, which suppresses the growth of Malassezia furfur, Staphylococcus aureus, and Staphylococcus capitis, and promotes the growth of Staphylococcus epidermidis.

5. The scalp microbiota improving composition according to claim 2, wherein the peptide content is 0.008% by mass or more.

6. The scalp microbiota improving composition according to claim 3, wherein the peptide content is 0.008% by mass or more.

7. The scalp microbiota improving composition according to claim 4, wherein the peptide content is 0.08% by mass or more.

8. The scalp microbiome improving composition according to claim 1, further comprising maltooligosaccharides.

9. The scalp microbiota improving composition according to claim 8, wherein the maltooligosaccharide is at least one selected from the group consisting of maltotriose, maltotetraose, and maltopentaose.

10. The scalp microbiota improving composition according to claim 9, wherein the maltooligosaccharide is maltotetraose.

11. A hair care product comprising a composition for improving the resident microbiota of the scalp according to any one of claims 1 to 10.

12. The hair care product according to claim 11, wherein the hair care product is selected from the group consisting of hair shampoo, hair conditioner, hair treatment, hair mask, scalp cleanser, scalp essence, hair tonic, and hair lotion.

13. A composition for improving the resident microbiota of the scalp according to any one of claims 1 to 10, which has a therapeutic effect on seborrheic dermatitis of the scalp.

14. A treatment for seborrheic dermatitis of the scalp, containing a peptide composed of L-lysine and L-arginine as an active ingredient.

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