Growth inhibitor for fungi of the genus Malassezia

A growth inhibitor using hibiscus flower, ivy leaf, royal jelly, and Scutellaria baicalensis extracts, along with N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride, effectively inhibits Malassezia fungi growth, particularly Malassezia globosa, to treat associated skin diseases.

JP7855838B2Active Publication Date: 2026-05-11TAISHO PHARMACEUTICAL CO LTD
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
TAISHO PHARMACEUTICAL CO LTD
Filing Date
2021-08-03
Publication Date
2026-05-11

AI Technical Summary

Technical Problem

There is a lack of effective drugs that directly inhibit the growth of Malassezia fungi, particularly Malassezia globosa and Malassezia restricta, which are associated with skin diseases such as vitiligo, seborrheic dermatitis, Malassezia folliculitis, atopic dermatitis, and acne.

Method used

A growth inhibitor containing hibiscus flower extract, ivy leaf/stem extract, royal jelly extract, Scutellaria baicalensis extract, and N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride solution is developed to suppress the growth of Malassezia fungi, particularly Malassezia globosa.

Benefits of technology

The inhibitor effectively suppresses the growth of Malassezia fungi, including Malassezia globosa, thereby addressing skin diseases and symptoms associated with these fungi.

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Abstract

To provide a growth inhibitor for fungi of the genus Malassezia.SOLUTION: The growth inhibitor for fungi of Malassezia genus comprises at least one selected as an active ingredient from the group consisting of hibiscus flower extract, Hedera helix leaf / stem extract, royal jelly extract, Rubus suavissimus leaf extract, Scutellaria baicalensis root extract, and N-[2-hydroxy-3-(trimethylammonio)propyl] chloride hydrolyzed keratin solution, and is preferably applied to skin or hair.SELECTED DRAWING: None
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Description

Technical Field

[0001] The present invention relates to a growth inhibitor against Malassezia fungi.

Background Art

[0002] Malassezia fungi are yeast-like fungi that are resident on human skin and are so-called lipidophilic fungi that require lipids for their growth. Also, depending on the state of the host, they are known as causative or exacerbating bacteria of skin diseases such as vitiligo, seborrheic dermatitis, Malassezia folliculitis, atopic dermatitis, psoriasis, and acne. Currently, Malassezia fungi are classified into 18 species, and Malassezia globosa and Malassezia restricta are species that are always detected from skin disease patients or healthy human skin (Non-Patent Documents 1 and 2). Among the above diseases, for example, as therapeutic agents for seborrheic dermatitis, topical steroid agents, non-steroidal anti-inflammatory topical agents, antifungal agents such as ketoconazole, etc. are known (Non-Patent Document 3).

Prior Art Documents

Non-Patent Documents

[0003]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0004] However, few drugs have been reported that directly inhibit the growth of Malassezia fungi, particularly Malassezia globosa and Malassezia restricta, which are found on human skin. Therefore, there is a need for active ingredients that can treat, improve, and prevent diseases and symptoms associated with fungi of the genus Malassezia. The present invention aims to provide a growth inhibitor for fungi of the genus Malassezia in order to solve the above-mentioned problems in the conventional approach. [Means for solving the problem]

[0005] The inventors of this invention conducted extensive research to solve the above problems and, as a result, discovered that at least one selected from the group consisting of hibiscus flower extract, ivy leaf / stem extract, royal jelly extract, Tencha extract, Scutellaria baicalensis extract, and N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride solution is suitable for a novel application, as it can suppress the growth of fungi of the genus Malassezia, particularly Malassezia globosa, thus completing the present invention.

[0006] In other words, the present invention is (1) A growth inhibitor against Malassezia fungi, characterized by containing at least one selected from the group consisting of hibiscus flower extract, ivy leaf / stem extract, royal jelly extract, tea extract, scutellaria baicalensis extract, and N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride solution as an active ingredient. (2) A growth inhibitor against Malassezia fungi as described in (1), which is for use on the skin and / or on the hair. (3) The growth inhibitor described in (1) or (2) wherein the fungus of the genus Malassezia is Malassezia globosa. That is the case. [Effects of the Invention]

[0007] This invention makes it possible to provide an inhibitor of growth of fungi of the genus Malassezia. [Modes for carrying out the invention]

[0008] The Malassezia fungal growth inhibitor of the present invention contains at least one selected from the group consisting of hibiscus flower extract, ivy leaf / stem extract, royal jelly extract, henbit extract, scutellaria baicalensis extract, and N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride solution, and is used for skin and / or hair. Each of the above agents can be of a quality commonly used in pharmaceuticals, quasi-drugs, or cosmetics as appropriate.

[0009] The hibiscus flower extract of the present invention is an extract obtained from the flowers of rosellus (scientific name: Hibiscus sabdariffa), a plant belonging to the Malvaceae family. The extraction method for the above extract is not particularly limited and can be carried out according to conventional methods. Any polar or nonpolar solvent can be used as the extraction solvent, for example, water, ethanol, propylene glycol, 1,3-butylene glycol, and mixtures thereof can be used. The above extract may be used as is, or it may be used after being concentrated, diluted, filtered, decolorized with activated carbon, deodorized, or precipitated with ethanol, as needed. Furthermore, the extracted solution may be concentrated to dryness, spray-dried, freeze-dried, or otherwise treated to obtain a dried product, which can then be used. Commercially available products can also be used.

[0010] The amount of hibiscus flower extract in the growth inhibitor for Malassezia fungi of the present invention is preferably 0.0001% to 20% by mass, and more preferably 0.001% to 10% by mass, relative to the total composition, when provided as a pharmaceutical, quasi-drug, cosmetic, or reagent.

[0011] The Hedera helix leaf / stem extract of the present invention is an extract obtained from the leaves and stems of Hedera helix, a plant belonging to the Araliaceae family. The extraction method for the above extract is not particularly limited and can be carried out according to conventional methods. Any polar or non-polar solvent can be used as the extraction solvent, for example, water, ethanol, propylene glycol, 1,3-butylene glycol, and mixtures thereof can be used. The above extract may be used as is, or it may be used after being concentrated, diluted, filtered, decolorized with activated carbon, deodorized, or precipitated with ethanol as needed. Furthermore, the extracted solution may be treated by concentrating to dryness, spray drying, freeze-drying, etc., and used as a dried product. Commercial products can also be used.

[0012] The amount of Hedera helix leaf / stem extract in the growth inhibitor for Malassezia fungi of the present invention is preferably 0.0001% to 20% by mass, and more preferably 0.001% to 10% by mass, relative to the total composition, when provided as a pharmaceutical, quasi-drug, cosmetic, or reagent.

[0013] The royal jelly extract of the present invention is an extract obtained by extracting secretions secreted from the pharyngeal gland or mandibular gland, which are produced in vivo from pollen and nectar of the European honeybee (Apis mellifera L.) or the Eastern honeybee (Apis indika Radoszkowski). The extraction method for the above extract is not particularly limited and can be carried out according to conventional methods. Any polar or non-polar solvent can be used as the extraction solvent, for example, water, ethanol, propylene glycol, 1,3-butylene glycol, and mixtures thereof can be used. The above extract may be used as is, or it may be used after being concentrated, diluted, filtered, decolorized with activated carbon, deodorized, or precipitated with ethanol, as needed. Furthermore, the extracted solution may be concentrated to dryness, spray-dried, freeze-dried, or otherwise treated to obtain a dried product, which can then be used. Commercially available products can also be used.

[0014] The amount of royal jelly extract in the growth inhibitor for Malassezia fungi of the present invention is preferably 0.0001% to 20% by mass, and more preferably 0.001% to 10% by mass, relative to the total composition, when provided as a pharmaceutical, quasi-drug, cosmetic, or reagent.

[0015] The Tencha extract of the present invention is an extract obtained from the leaves of the plant known as sweet tea (scientific name: Rubus suavissimus), which belongs to the Rosaceae family. The extraction method for the above extract is not particularly limited and can be carried out according to conventional methods. Any polar or nonpolar solvent can be used as the extraction solvent, for example, water, ethanol, propylene glycol, 1,3-butylene glycol, and mixtures thereof can be used. The above extract may be used as is, or it may be used after being treated by concentration, dilution, filtration, decolorization with activated carbon, deodorization, ethanol precipitation, etc., as needed. Furthermore, the extracted solution may be treated by concentration to dryness, spray drying, freeze-drying, etc., and used as a dried product. Commercial products can also be used.

[0016] The amount of tencha extract in the growth inhibitor for Malassezia fungi of the present invention is preferably 0.0001% to 20% by mass, and more preferably 0.001% to 10% by mass, relative to the total composition, when provided as a pharmaceutical, quasi-drug, cosmetic, or reagent.

[0017] The Scutellaria extract of the present invention is an extract obtained from the roots of Scutellaria baicalensis, a plant belonging to the Lamiaceae family. The extraction method of the above extract is not particularly limited and can be carried out according to conventional methods. As the extraction solvent used for extraction, either a polar solvent or a nonpolar solvent can be used. For example, water, ethanol, propylene glycol, 1,3-butylene glycol, and mixtures thereof can be used. The above extract may be used as the extracted solution as it is, or if necessary, it may be used after being subjected to treatments such as concentration, dilution, filtration, decolorization with activated carbon, deodorization, and ethanol precipitation. Furthermore, the extracted solution may be subjected to treatments such as concentration to dryness, spray drying, and freeze drying, and used as a dried product. Commercially available products can also be used.

[0018] When the Scutellaria extract is used in the growth inhibitor of Malassezia fungi of the present invention and is provided as a pharmaceutical, quasi-drug, cosmetic, or reagent, the content thereof is preferably 0.0001% by mass to 20% by mass, more preferably 0.001% by mass to 10% by mass, based on the entire composition.

[0019] The N-[2-hydroxy-3-(trimethylammonio)propyl] hydrolyzed keratin chloride solution of the present invention is obtained by cationizing α-keratose extracted and purified while maintaining the amino acid balance of the keratin protein derived from wool. It may be used as the extracted and purified solution as it is, or if necessary, it may be used after being subjected to treatments such as concentration, dilution, filtration, decolorization with activated carbon, deodorization, and ethanol precipitation. Furthermore, the extracted solution may be subjected to treatments such as concentration to dryness, spray drying, and freeze drying, and used as a dried product. Commercially available products can also be used.

[0020] When the N-[2-hydroxy-3-(trimethylammonio)propyl] hydrolyzed keratin chloride solution is used in the growth inhibitor of Malassezia fungi of the present invention and is provided as a pharmaceutical, quasi-drug, cosmetic, or reagent, the content thereof is preferably 0.0001% by mass to 20% by mass, more preferably 0.001% by mass to 10% by mass, based on the entire composition.

[0021] Examples of the Malassezia fungus of the present invention include Malassezia globosa, Malassezia restricta, Malassezia furfur, Malassezia sympodialis, Malassezia pachydermatis, etc., and preferably, it is Malassezia globosa.

[0022] The growth inhibitor against the Malassezia fungus of the present invention is preferably used for human skin (including scalp) or hair.

Examples

[0023] Examples and test examples are described below to more specifically explain the present invention, but the present invention is not limited by these examples etc.

[0024] (Test Example 1: Growth Inhibition Test of Malassezia globosa) In order to evaluate the growth inhibitory effect against Malassezia globosa, it was tested by the following method. (Preparation of Test Medium) The medium was prepared so that the final concentrations were as follows. Artificial sebum 2% (mixture of triolein 58.6%, glyceryl distearate 15.6%, palmitic acid 6.1%, myristic acid 2.2%, pentadecanoic acid 1.5%, oleic acid 4.7%, squalene 11.3%) simulating human scalp sebum, glucose 1%, Bile salt 0.8%, Yeast extract 0.2%, glycerin monostearate 0.05%, glycerin 1%, self-emulsifying glyceryl monostearate 1% were mixed and sterilized, and then a predetermined amount of chromoagar candida (Kanto Chemical) was added and used. (Preparation of Inoculum) Malassezia globosa was pre-cultured in a modified LNA medium (32 °C, 3 days, static), and the obtained test bacteria were collected with a sterile loop, suspended and washed in PBS. The washed bacterial suspension had a bacterial amount of about 10 7The bacterial solution was diluted with PBS to a concentration of CFU / mL and used as the inoculum. (Preparation of test substance) Hibiscus flower extract, ivy leaf / stem extract, royal jelly extract, tea extract, scutellaria baicalensis extract, N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride solution, and 1,3-butylene glycol were diluted four-fold with purified water and filtered and sterilized. The hibiscus flower extract used was Organic <Hibiscus> (manufactured by Maruzen Pharmaceutical Co., Ltd.), the ivy leaf / stem extract was Ivy Extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.), the royal jelly extract was Royal Jelly Extract B (manufactured by Ichimaru Falcos Co., Ltd.), the tea extract was Sweet Tea Extract BGW (manufactured by Maruzen Pharmaceutical Co., Ltd.), the scutellaria baicalensis extract was Scutellaria baicalensis Extract BG-JC (manufactured by Maruzen Pharmaceutical Co., Ltd.), and the N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride solution was Proticute C Alpha (manufactured by Ichimaru Falcos Co., Ltd.). (Antibacterial testing) 200 μL each of the prepared test substance, 1,3-butylene glycol, and purified water (as a positive control) were added to each well of a 24-well sterile plate with a flat bottom. Then, 300 μL of the prepared artificial sebum-added medium was added to each well and quickly mixed. 1,3-butylene glycol was used as the solvent control. After the medium solidified, 10 μL of the inoculum was added to the center of each well and incubated at 32°C for 3 days. Since the chromogenic enzyme substrate contained in Chromoagar Candida causes the grown bacteria to turn red, the growth of the bacteria in each well was visually compared with that of the positive control and solvent control. The viability of the bacteria was evaluated on a 5-point scale (0%, 25%, 50%, 75%, 100%) with the positive control set at 100%.

[0025] (Test results) Table 1 shows the average survival rates of bacteria tested with n=2 for each case.

[0026] [Table 1]

[0027] As is clear from Table 1, hibiscus flower extract, ivy leaf / stem extract, royal jelly extract, henbit extract, scutellaria baicalensis extract, and N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride solution were all confirmed to have a higher growth inhibitory effect than the solvent control 1,3-butylene glycol. This suggests that at least one of the group consisting of hibiscus flower extract, ivy leaf / stem extract, royal jelly extract, henbit extract, scutellaria baicalensis extract, and N-[2-hydroxy-3-(trimethylammonio)propyl]hydrolyzed keratin chloride solution has a growth inhibitory effect on Malassezia globosa. [Industrial applicability]

[0028] The Malassezia fungal growth inhibitor of the present invention is expected to suppress the abnormal proliferation of Malassezia fungi and normalize the imbalance of commensal bacteria on the skin, scalp, or hair. The Malassezia fungal growth inhibitor of the present invention can be used in the fields of cosmetics, quasi-drugs, and pharmaceuticals for the treatment, improvement, and prevention of skin diseases and symptoms associated with Malassezia fungi, such as tinea versicolor, seborrheic dermatitis, Malassezia folliculitis, atopic dermatitis, psoriasis, and acne.

Claims

1. A growth inhibitor for fungi of the genus Malassezia, characterized by containing hibiscus flower extract extracted using an aqueous ethanol solution as a solvent as an active ingredient.

2. A growth inhibitor against Malassezia fungi according to claim 1, for use on skin and / or hair.

3. The growth inhibitor according to claim 1 or 2, wherein the fungus of the genus Malassezia is Malassezia globesa.