JP7104956B2 - Melanocyte differentiation induction inhibitor and method of using the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to an agent for suppressing induction of differentiation from stem cells to melanocytes, and a composition for improving or treating pigmentary disorders or improving spots containing the agent for inducing differentiation.

Melanocytes are cells that synthesize melanin pigments and determine skin and coat colors of animals. Melanocytes are derived from neural crest cells that derive from the neural tube, which is fundamental to vertebrate development. Neural crest cells migrate symmetrically ventrally from the neural tube into the dermis and mature while proliferating. Finally, after the neural crest cells settle in the hair follicle, they further differentiate and mature into melanocytes and mature.

In addition, in the hair follicle, undifferentiated melanocyte stem cells exist near the bulge region together with mature melanocytes. The undifferentiated melanocyte stem cells are believed to self-proliferate, undergo immature melanoblasts as necessary, and supply mature melanocytes to the epidermis and hair matrix. The supplied mature melanocytes supply pigments to the skin and hair by transferring melanosomes to surrounding keratinocytes. Thus, melanocytes have various stages of differentiation.

Differentiation and proliferation of melanocytes and abnormalities in the mechanism of melanin synthesis cause various pigment disorders and age spots. For example, when neural crest cell migration is abnormal, neural crest cells that should migrate to the epidermal layer remain in the dermis. The persistence in the dermis causes symmetric dermal melanocytosis, which is late-onset due to various stimuli after birth. The lesions of this disease are brownish and bilaterally symmetrical. The disease is overwhelmingly common in women, and it often develops in the late teens to twenties. Estrogen involvement in symmetric dermal melanocytosis has therefore been proposed. However, the cause is still unclear in many points.

In addition, melasma is overwhelmingly common in women, and it is a blemish that frequently develops especially in women in their 30s. The clinical manifestation of chloasma is bilaterally symmetric flat brown spots that occur on the cheeks, around the mouth, and on the forehead. The onset of chloasma begins in the second to third month of pregnancy, becomes progressively more severe, and gradually disappears with the onset of menstruation after delivery. However, melasma can persist for a long time and extend into the postmenopausal period. Furthermore, oral contraceptives containing female hormones are known to induce melasma.

By the way, a representative external factor acting on the proliferation and differentiation of melanocytes is ultraviolet rays. Ultraviolet rays act on epidermal cells to promote the secretion of various melanocyte proliferation and differentiation-promoting factors. It is also known that ultraviolet rays act directly on melanocytes and enhance the expression of receptors for various melanocyte activating factors. Senile pigment spots are caused by the repeated increase of melanocytes and enhancement of melanin synthesis due to ultraviolet rays over many years. Nearly 100% of Japanese people in their 60s have senile spots, and there is no difference in frequency between men and women. Areas that are relatively exposed to sunlight, such as the face, shoulders, back, and hands, are the most likely to develop senile pigment spots, and brown to dark brown flat spots appear.

As described above, when abnormalities occur in melanocyte development, differentiation, proliferation, and melanin synthesis, various pigment disorders and age spots occur. Since these diseases appear as a direct external expression system, they impose a heavy mental burden on patients, and are one of the factors that hinder QOL (quality of life). Therefore, identification of melanocyte regulatory factors is essential to fundamentally ameliorate these diseases.

On the other hand, as a whitening agent that regulates melanocytes, many whitening agents have been developed that focus on the effect of inhibiting the activity of tyrosinase, an enzyme involved in melanin synthesis. For example, kojic acid, hydroquinone, L-ascorbic acid and the like are well known as substances having tyrosinase activity inhibitory effects. In addition, tyrosinase activity inhibitors and melanogenesis inhibitors containing natural ingredients as active ingredients, such as extracts of plants belonging to the genus Musa (Patent Document 1) and extracts of Emberia, a plant belonging to the family Aspergillus (Patent Document 2), have been developed. However, these tyrosinase inhibitors only act mainly on mature melanocytes (which express tyrosinase and have the ability to synthesize melanin), and cannot be said to fundamentally control melanocytes.

As described above, melanocytes undergo various stages of differentiation (neural crest cells, melanocyte stem cells, melanoblasts, etc.) before reaching mature melanocytes, and abnormal differentiation causes various pigment disorders and age spots. be Therefore, it is important to identify a factor that controls this melanocyte differentiation itself in order to fundamentally solve pigmentary disorders and blemishes. However, in the past, screening systems using melanoma cells (produced by melanocyte canceration), terminally differentiated melanocytes, mushroom-derived tyrosinase, etc. were mainly used to search for melanocyte regulatory factors. Therefore, no search for a factor controlling melanocyte differentiation has been made in the past.

So far, seaweed extracts have also been reported to be involved in the control (inhibition or promotion) of melanin production. For example, an extract of Alaria praelonga Kjellman, which belongs to the genus Ainuwakame, belongs to the order Laminariales, Lagoonidae, and has a melanogenesis inhibitory effect (Patent Document 3).

On the other hand, the extract of Ecklonia kurome of the genus Ecklonia kurome of the Laminaria order Laminariaceae Ecklonia kurome has a β-glucuronidase inhibitory action and is applied to foods and cosmetics (Patent Document 4). (Agarum clathratum or Agarum cribrosum) extract is known to be used as a hair nourishing composition (Patent Document 5) and a cosmetic composition (Patent Document 6). In addition, the extract of Sargassum fulvellum of the genus Sargassum fulvellum of the family Sargassum genus Sargassum fulvellum of the order Fucus, has an apoptosis inhibitory action (Patent Document 7), a dermal papilla cell proliferation promoting action (Patent Document 8), and a melanin production inhibitory action (Patent Document 9). It has been proposed to use it as an external skin preparation, a hair restorer, and a whitening agent. However, nothing has been known about the effects of these seaweeds on melanocyte differentiation itself.

JP-A-2008-56587 JP 2005-289922 A JP 2013-103927 A JP 2006-045188 A JP-A-2003-81861 JP 2017-052706 A JP 2009-242325 A JP 2007-131571 A JP-A-10-330220

As described above, the identification of factors that control melanocyte differentiation itself is important for the fundamental resolution of pigmentary disorders and blemishes.

Therefore, in view of the actual situation described above, the present invention finds a material having an activity of suppressing the differentiation of stem cells into melanocytes, and provides an unprecedented composition for improving or treating fundamental pigmentary disorders and a composition for improving blemishes. intended to

In order to solve the above problems, the present inventors have investigated all of melanocyte development, differentiation, proliferation and melanin synthesis, instead of conventional screening systems using melanoma cells, terminally differentiated melanocytes, and mushroom-derived tyrosinase. Using a screening system capable of inducing differentiation from stem cells to melanocytes that can be reproduced in vitro, we searched for materials that inhibit the differentiation itself from stem cells to melanocytes. The inventors have found that one or more seaweed extracts have an excellent effect of suppressing the differentiation of stem cells into melanocytes, and have completed the present invention.

That is, the present invention includes the following inventions.
(1) An inhibitor of induction of differentiation from stem cells to melanocytes, containing as an active ingredient an extract of one or more seaweeds selected from black seaweed, aname, and sargassum.
(2) A composition for ameliorating or treating pigmentary disorders, which contains the inhibitor of induction of differentiation from stem cells to melanocytes according to (1).
(3) A blemish-improving composition containing the agent for suppressing induction of differentiation from stem cells to melanocytes according to (1).

According to the present invention, differentiation of melanocytes can be fundamentally controlled by significantly suppressing induction of differentiation from stem cells to melanocytes. Therefore, the present invention can greatly contribute to the treatment, prevention, and improvement of pigmentation disorders and blemishes associated with melanocytes, and can be applied to the fields of medicine, pharmaceuticals, quasi-drugs, beauty, and health. be.

The present invention will be described in detail below.
The inhibitor of differentiation induction from stem cells to melanocytes of the present invention (hereinafter referred to as "melanocyte differentiation induction inhibitor") is derived from Ecklonia kurome, Agarum clathratum or Agarum cribrosum, and Sargassum fulvellum. It contains one or more selected seaweed extracts as active ingredients.

According to the melanocyte differentiation induction inhibitor of the present invention, differentiation of melanocytes can be controlled by suppressing differentiation from stem cells to melanocytes. In addition, according to the melanocyte differentiation induction inhibitor of the present invention, by controlling the differentiation from stem cells to melanocytes, it is possible to fundamentally prevent, improve and treat melanocyte-related diseases such as pigmentation disorders and age spots. can. Furthermore, the melanocyte differentiation induction inhibitor of the present invention can also be used as a research reagent for suppressing the differentiation of stem cells into melanocytes.

Ecklonia kurome used in the present invention is a seaweed of the genus Ecklonia of the Laminaria order Laminariaceae, mainly distributed from the middle and southern coast of Honshu to Kyushu, and the Seto Inland Sea and the Sea of Japan side of Niigata Prefecture and southwards. The size of the algal body is 40-50 cm, and the largest one is 1 m, and it is mainly used as food.

Agarum clathratum or Agarum cribrosum used in the present invention is a seaweed belonging to the genus Agaricus, belonging to the order Laminariales, the family Agaricaceae, distributed mainly throughout Hokkaido, and characterized by numerous pores. The growth depth is deep, and you can't see it unless you dive.

Sargassum fulvellum used in the present invention is a seaweed belonging to the genus Sargassum, belonging to the family Sargassum fulvellum, of the order Fucus, and distributed mainly from Kyushu to the entire Pacific coast of Honshu, and in the Sea of Japan, to the vicinity of Echigo. The algal body is lanceolate and characterized by notches.

Kurome, Aname, and Sargassum can be obtained from the above-mentioned growing regions, respectively. In the present invention, it is preferable to use the whole seaweed (whole plant) as the raw material for extracting the seaweed. ), sporophylls, roots, and the like. For extraction, the seaweed itself may be used as it is, or may be subjected to treatments such as drying, pulverization, and shredding.

The extraction method is not particularly limited, but it can be carried out by stirring or column extraction using water, hot water, or a mixed solvent of water and an organic solvent. As the organic solvent, alcohols, ethers, esters and the like can be used, and water-soluble organic solvents such as ethanol, methanol, acetone, n-propanol, t-butanol, propylene glycol and 1,3-butylene glycol can be used. Preferably, one or more of these may be used. A particularly preferred extraction solvent includes water or a water-ethanol mixed polar solvent. The amount of solvent used is not particularly limited, and may be, for example, 10 times or more, preferably 20 times or more, relative to the seaweed (dry weight). For convenience of operation, it is preferably 100 times or less. The extraction temperature and time depend on the type of solvent used, but can be exemplified at 10 to 100° C., preferably 30 to 90° C., for 30 minutes to 24 hours, preferably 1 to 10 hours. In addition, the extract may be used as an extracted solution, but if necessary, concentration (concentration by organic solvent, vacuum concentration, membrane concentration, etc.), dilution, filtration, It may be used after being treated with activated carbon or the like for decolorization, deodorization, ethanol precipitation, or the like. Furthermore, the extracted solution may be subjected to a treatment such as concentration to dryness, spray drying, freeze drying, etc., and used as a dried product.

The seaweed extract thus obtained is used as an active ingredient of the melanocyte differentiation induction inhibitor of the present invention. The melanocyte differentiation induction inhibitor of the present invention can be used as a drug, quasi-drug, cosmetic, or food and drink. In addition, one or more seaweed extracts selected from the above-mentioned kurome, aname, and sargassum can also be used for the production of pharmaceuticals, quasi-drugs, cosmetics, or food and drink. In particular, the melanocyte differentiation induction inhibitor of the present invention can be used as a composition for improving or treating pigmentation disorders or a composition for improving dark spots, or for the production of the composition. One of the extracts of kurome, aname, and sargassum may be used, or two or three of them may be used in combination. When the extracts of Kurome, Aname, and Sargassum are used together, the combination and mixing ratio are not limited.

Here, pigmentary disorders include, for example, symmetrical dermal melanocytosis, chloasma, senile pigmentary macules, freckles, Riehl's melanosis, tribomelanoderma, hereditary contralateral pigmentary disorders, Addison's disease , actinic petaloid pigment spots, dyschromic erythema fixed, and the like.

Furthermore, when using the melanocyte differentiation induction suppressing agent of the present invention as a drug, quasi-drug, cosmetic or food and drink, the instruction manual or package includes one or It can be labeled as containing two or more seaweed extracts and having melanocyte differentiation induction inhibitory activity.

When the melanocyte differentiation induction inhibitor of the present invention is used as a drug or quasi-drug, the dosage form is not particularly limited. Examples include formulations (ointments (creams), solutions, extracts, lotions, emulsions, etc.) and injections. The pharmaceutical or quasi-drug contains one or more seaweed extracts selected from kurome, aname, and sargassum, as well as auxiliary agents, stabilizers, wetting agents, emulsifiers, absorption enhancers and Any combination of pharmaceutically acceptable carriers such as surfactants can be used.

When the melanocyte differentiation induction inhibitor of the present invention is used as a cosmetic, the dosage form is not particularly limited, but examples include creams, lotions, foams, essences, foundations, packs, sticks and powders. are mentioned. The cosmetic contains one or more seaweed extracts selected from kurome, aname, and sargassum, as well as oils, surfactants, ultraviolet absorbers, and alcohols that are commonly used as cosmetic ingredients. chelating agents, pH adjusters, preservatives, thickeners, pigments, perfumes and the like can be arbitrarily combined.

The amount of one or more seaweed extracts selected from Kurome, Aname, and Sargassum in the melanocyte differentiation induction inhibitor of the present invention is not particularly limited, but is 0.00001 to 10% by weight of the total composition. %, most preferably 0.0001 to 1% by weight. If the content is less than 0.00001% by weight of the total composition, the melanocyte differentiation-inducing inhibitory effect may not be sufficiently exhibited.

By applying the melanocyte differentiation induction inhibitor of the present invention described above to animals including humans, it is possible to suppress the induction of differentiation from stem cells to melanocytes, and to treat, prevent, or improve pigmentation disorders or age spots. can be done. The melanocyte differentiation induction suppressing activity from stem cells to melanocytes of the melanocyte differentiation induction inhibitor of the present invention is, for example, a melanocyte marker gene Mitf-M (melanocyte-specific microphthalmia-associated transcription factor: Melanocyte-specific Microphthalmia-associated transcription factor) ( Tachibana M. Pigment Cell Res. (2000) 13(4):230-40.) and Tyrp1 (Tyrosinase-related protein 1) (Sarangarajan R, Boissy RE. Pigment Cell Res. (2001) 14( 6):437-44.) can be evaluated and confirmed by the expression level. Measurement of these melanocyte marker gene expression levels may be performed by any method known to those skilled in the art. For example, at the mRNA level, RT-PCR using primers and probes specific to the melanocyte marker gene, quantitative PCR and northern blotting can be performed, and at the protein level, it can be performed by specific to the protein encoded by the melanocyte marker gene. It can be performed by immunological methods such as ELISA using a specific antibody, flow cytometry, western blotting and the like.

EXAMPLES The present invention will be described in more detail below using examples, but the technical scope of the present invention is not limited to these examples.

[Example 1] Production example of extracts of kurome, aname, and sargassum Seaweed extracts of kurome, aname, and sargassum were produced as follows. Whole seaweed was used as an extraction material in Production Examples 1 to 12.

(Production Example 1) Preparation of Hot Water Extract of Kurome 10 g of dried Kurome was added to 200 mL of water and extracted at 95 to 100° C. for 2 hours. The resulting extract was filtered, and the filtrate was concentrated and freeze-dried to obtain 2.1 g of a hot water extract of kuromae.

(Production Example 2) Preparation of 50% Ethanol Extract of Kurome Extraction was performed by immersing 10 g of dried Kurome in 200 mL of a 50% (V/V) ethanol aqueous solution at room temperature for 7 days. After filtering the resulting extract, it was concentrated to dryness using an evaporator to obtain 1.1 g of a 50% ethanol extract of black urchin.

(Production Example 3) Preparation of Ethanol Extract of Kurome 10 g of dried Kurome was immersed in 200 mL of ethanol at room temperature for 7 days for extraction. After filtering the resulting extract, it was concentrated to dryness using an evaporator to obtain 0.2 g of an ethanol extract of Kurome.

(Manufacturing Example 4) Preparation of 1,3-butylene glycol (1,3-BG) extract of kurome 10 g of dried kurome was added to 200 mL of a 50% (V/V) 1,3-BG aqueous solution at room temperature for 7 days. Extraction was performed by immersion. The resulting extract was filtered to obtain 192 g of a 1,3-BG extract of Kurome.

(Production Example 5) Preparation of hot water extract of sea cucumber 10 g of dried sea cucumber was added to 200 mL of water and extracted at 95 to 100°C for 2 hours. The resulting extract was filtered, and the filtrate was concentrated and freeze-dried to obtain 2.0 g of hot water extract of sea cucumber.

(Production Example 6) Preparation of 50% ethanol extract of sea cucumber Extraction was performed by immersing 10 g of dried sea cucumber in 200 mL of a 50% (V/V) ethanol aqueous solution at room temperature for 7 days. After filtering the resulting extract, it was concentrated to dryness using an evaporator to obtain 1.0 g of a 50% ethanol extract of sea cucumber.

(Manufacturing Example 7) Preparation of ethanol extract of sea cucumber Extraction was performed by immersing 10 g of dried sea cucumber in 200 mL of ethanol at room temperature for 7 days. After filtering the resulting extract, it was concentrated to dryness using an evaporator to obtain 0.1 g of an ethanol extract of sea cucumber.

(Production Example 8) Preparation of 1,3-butylene glycol (1,3-BG) extract of sea cucumber 10 g of dried sea cucumber is added to 200 mL of a 50% (V / V) 1,3-BG aqueous solution at room temperature for 7 days. Extraction was performed by immersion. The resulting extract was filtered to obtain 190 g of a 1,3-BG extract of sea cucumber.

(Production Example 9) Preparation of Hot Water Extract of Sargassum Sargassum 10 g of dried Sargassum was added to 200 mL of water and extracted at 95 to 100° C. for 2 hours. The resulting extract was filtered, and the filtrate was concentrated and freeze-dried to obtain 2.0 g of a hot water extract of Sargassum.

(Production Example 10) Preparation of 50% Ethanol Extract of Sargassum Sargassum 10 g of dried sargassum was immersed in 200 mL of 50% (V/V) ethanol aqueous solution at room temperature for 7 days for extraction. After filtering the resulting extract, it was concentrated to dryness using an evaporator to obtain 1.0 g of a 50% ethanol extract of Sargassum.

(Production Example 11) Preparation of Ethanol Extract of Sargassum Sargassum 10 g of dried Sargassum was immersed in 200 mL of ethanol at room temperature for 7 days for extraction. After filtering the resulting extract, it was concentrated to dryness using an evaporator to obtain 0.2 g of an ethanol extract of Sargassum.

(Production Example 12) Preparation of 1,3-butylene glycol (1,3-BG) extract of sargassum Extraction was performed by immersion. The obtained extract was filtered to obtain 185 g of 1,3-BG extract of Sargassum.

[Example 2] Evaluation of the differentiation-inducing inhibitory effect of the extracts of black bream, red kelp, and sargassum from stem cells to melanocytes In the following, using the extracts of black bream, red kelp, and sargassum produced in Example 1, from stem cells The melanocyte differentiation induction inhibitory effect was evaluated, and the effect of the extracts of Kurome, Aname, and Sargassum as a melanocyte differentiation induction inhibitor was confirmed.

1. Experimental Example 1 Evaluation of the inhibitory effect of the extracts of Kurome, Aname, and Sargassum on differentiation induction from stem cells to melanocytes (quantitative melanin test)
In this experimental example, a melanocyte differentiation induction system from mouse ES cells previously developed by Yamane et al. 216, Issue 4-5, pp. 450-458) were used to study the effects of extracts of kurome, sea bream, and sargassum. By using this induction system, it becomes possible to evaluate materials at all stages from melanocyte development to maturation. Details are described below.

MMC-treated MEFs were cultured in a 35-mm petri dish in a confluent state, and 1×10 ⁵ to 2×10 ⁵ mouse ES cells were seeded thereon and pre-cultured at 37° C. in a 5% CO ₂ incubator. The medium used was DMEM supplemented with chemicon ES cell additive factors (L-glutamine solution, 2-mercaptoethanol solution, nucleoside solution, non-essential amino acid solution and ESGRO) at the recommended concentrations, followed by 15% FBS. It was added.

Then, the ST2 cells were cultured on a 24-well plate until confluent, and 250 to 500 of the cultured ES cells separated from the MEFs were seeded there. The culture was cultured in a differentiation-inducing medium containing α-MEM supplemented with 10% FBS, 100 nM DEX, 20 pM bFGF, 10 pM CT and 100 ng/mL EDN3 to induce differentiation of ES cells into melanocytes. Microscopic observation revealed that ES cell colonies formed on the ST2 cells began to spread 6 days after induction, and melanocytes appeared around the colonies around 18 days after induction. By 24 days after induction, the emergent melanocytes were observed to further synthesize melanin. From the above, it was confirmed that the development, differentiation and melanin synthesis of melanocytes could all be reproduced by using this induction system.

In this induction system, 10 μg/mL extracts of Japanese blackberry, Japanese tangerine, and Sargassum sargassum were continuously added to the differentiation-inducing medium described above to induce differentiation for 24 days. After that, the relative cell number was quantified using Cell Counting Kit-8. On the other hand, after quantifying the number of cells, the cells were washed three times with PBS(-) and then lysed with 2N NaOH at 60°C for 2 hours, and the absorbance at 475 nm of the lysate was measured. As a result, the amount of melanin synthesized per cell number decreased in a dose-dependent manner.
The results of these tests are shown in Table 1 below.

As shown in Table 1, the extracts of Kurome, Aname, and Sargassum (Production Examples 1 to 12) were found to have a remarkable melanocyte differentiation-inducing inhibitory effect. From the above, it has been clarified that the extracts of kuromime, aname, and sargassum have an extremely excellent inhibitory effect on melanocyte differentiation induction from stem cells, and the effect of the extracts of kuromime, aname, and sargassum as a melanocyte differentiation induction inhibitor. confirmed.

2. Experimental Example 2 Evaluation of the inhibitory effect of the extracts of Kurome, Aname, and Sargassum on differentiation induction from stem cells to melanocytes (gene expression analysis)
In the same manner as in Test Example 1, mouse ES cells were induced to differentiate into melanocytes, and the efficiency of differentiation into melanocytes was evaluated using the expression of melanocyte-specific marker genes (Mitf-M and Tyrp1) as an indicator.

Specifically, 10 μg/mL of the extracts of Kurome, Aname, and Sargassum were continuously added to the differentiation-inducing medium described above to induce differentiation for 24 days. On the 24th day of induction of differentiation, the cells were collected, washed twice with PBS(-), and RNA was extracted from the cells with Trizol Reagent (Invitrogen). Then, using a 2-STEP real-time PCR kit (Applied Biosystems), the extracted RNA was reverse transcribed into cDNA, and then ABI7300 (Applied Biosystems) was used to use the obtained cDNA as a template, and the following primer sets were used. Real-time PCR (95°C: 15 seconds, 60°C: 30 seconds, 40 cycles) was performed. Other operations were carried out according to prescribed methods.

Primer set for Mitf-M:
5'-TGCCTTGTTTATGGTGCCTTCT-3' (SEQ ID NO: 1), and
5'-TCCCTCTACTTTCTGTAATTCCAATTC-3' (SEQ ID NO: 2)
Primer set for Tyrp1:
5'-CAACGCTATGCTGAGGACTATGA-3' (SEQ ID NO: 3), and
5'-GCGGCTATCAGACCATGGA-3' (SEQ ID NO: 4)
Primer set for Gapdh:
5'-TGCACCACCAACTGCTTAGC-3' (SEQ ID NO: 5), and
5'-TCTTCTGGGTGGCAGTGATG-3' (SEQ ID NO: 6)

Regarding the differentiation induction efficiency of each cell into melanocytes, the expression levels of the melanocyte marker genes (Mitf-M and Tyrp1) in cells induced to differentiate without the addition of extracts of Kurome, Aname, and Sargassum were measured using Gapdh, an internal standard. The melanocyte-specific marker gene relative expression level calculated as a ratio to the mRNA expression level is set to 100, and the melanocyte-specific marker in each cell induced to differentiate by adding extracts of Kurome, Aname, and Sargassum. Gene relative expression values were calculated and evaluated.
The results are shown in Table 2 below.

As shown in Table 2, the extracts of Kurome, Aname, and Sargassum exhibited a remarkable melanocyte differentiation-inducing inhibitory effect. On the other hand, arbutin, a conventional skin-whitening agent, did not exhibit melanocyte differentiation-inducing inhibitory effects.

The melanocyte differentiation induction inhibitor of the present invention can treat, prevent and improve pigmentation disorders and age spots. For example, the use of one or more seaweed extracts selected from kurome, aname, and sargassum, which are found in the present invention, leads to a fundamental resolution of pigmentation disorders and blemishes. By introducing one or more seaweed extracts selected from kurome, aname, and sargassum, which are found in the present invention, by oral administration, direct injection to the skin, application, adhesion, etc., differentiation of undifferentiated cells into melanocytes can be suppressed. Therefore, the present invention can be used in the field of manufacturing pharmaceuticals, quasi-drugs, and cosmetics for the treatment and/or prevention of pigmentation disorders and age spots.

Claims (3)

An agent for suppressing induction of differentiation from stem cells to melanocytes, containing a hot water extract of kurome as an active ingredient. A composition for ameliorating or treating pigmentary disorders associated with abnormal differentiation of melanocytes, comprising the agent for suppressing induction of differentiation from stem cells to melanocytes according to claim 1 . A composition for improving blemishes associated with abnormal melanocyte differentiation, comprising the agent for suppressing induction of differentiation from stem cells to melanocytes according to claim 1 .