JP2011105644A - Melanin uptake inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To find a naturally occurring substance that is highly safe, inexpensive, can be used daily and is excellent in melanin uptake inhibitory action, and to provide a melanin uptake inhibitor containing the same as an active ingredient. <P>SOLUTION: The melanin uptake inhibitor contains an extract of one kind or two kinds more plant chosen from the group consisting of Acer palmatum, Aspalathus linearis, Artemisia princeps leaf, oolong tea, Artemisia capillaris flower, Scutellaria baicalensis root, Arnica montana L., Rosa centifolia, Ginkgo biloba L., Houttuynia cordata, Eriobotrya japonica, Humulus lupulus, Uncarina gambir, Hydrangea serrata and Urtica thubergiana as the active ingredient. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a melanin uptake inhibitor.

  Melanin also plays a role in protecting the body from ultraviolet rays in the skin, but overproduction and uneven accumulation cause skin darkening and spots. In general, melanin is converted from tyrosine to dopa and from dopa to dopaquinone by the action of the enzyme tyrosinase biosynthesized in pigment cells, and then formed through intermediates such as 5,6-dihydroxyindophenol. ing.

  Therefore, conventionally, in order to prevent, treat, or improve skin darkness (skin pigmentation), spots, buckwheat, etc., it inhibits the activity of tyrosinase involved in the production of melanin, or suppresses the production of melanin Has been focused on the development of the components (see Patent Documents 1 to 4).

  On the other hand, the melanin formed as described above is synthesized and stored in melanosomes (vesicles) in pigment cells, and is taken up as epithelial cells (keratinocytes) as melanosomes by phagocytosis (phagocytosis). It is known to blacken (see Patent Document 5). Therefore, if the uptake of melanosomes in epidermal cells (keratinocytes) can be suppressed, it is considered that skin darkness (skin pigmentation), spots, freckles, etc. can be prevented, treated or improved.

JP 2002-370962 A JP 2004-83488 A JP 2001-213757 A JP 2002-201222 A JP 2008-24691 A

  The present invention finds a natural product that is safe and inexpensive, can be used on a daily basis, and has an excellent melanin uptake inhibitory effect, and contains it as an active ingredient. The purpose is to provide.

  The present invention relates to one or more kinds of plants selected from the group consisting of Japanese maple, Asparagus serie Alice, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Atlantic rose, Ginkgo biloba, Juniper, Loquat, Hops, Acacia, Sweet tea and Nettle. A melanin uptake inhibitor comprising an extract from the above as an active ingredient.

  According to the present invention, it is possible to provide a melanin uptake inhibitor that has high safety, is inexpensive and can be used on a daily basis, and has an excellent action of suppressing melanin uptake.

Embodiments of the present invention will be described below.
The melanin uptake inhibitor of the present embodiment is 1 selected from the group consisting of Japanese maple, Asparasaslinearias, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rosewood, Ginkgo, Jujuk, Biwa, Hop, Asenyaku, Sweet tea and Nettle. Extracts from seeds or two or more plants are contained as active ingredients.

  In the present embodiment, the “extract” includes an extract obtained by using a plant as an extraction raw material, a diluted solution or a concentrated solution of the extract, a dried product obtained by drying the extract, or a roughly purified product thereof. Any of the purified products are included.

  Extraction raw materials used in the present embodiment are Japanese maple, asparagus linen alice, guinea, oolong tea, chinococcus, hornon, arnica, rose, ginkgo, jujuak, loquat, hop, asenyaku, sweet tea or nettle.

  Acer palmatum (scientific name: Acer palmatum) is a deciduous sub-high tree belonging to the genus Acer palmaceae, and is also referred to as Acer palmatum, Acer palmatum, Aca palmae and the like. Japanese maple is distributed in Shikoku, Kyushu, southern Korea, eastern China, etc., and is easily available from these regions. The constituent part of the Japanese maple used as the extraction raw material is not particularly limited, and examples thereof include a leaf part, a branch part, a root part, a bark part, a seed part, or a mixture of these parts, preferably a leaf part. .

  Asparathus lineis (scientific name: Aspalathus linearis, also known as Rooibos) is a deciduous shrub belonging to the genus Asparathus, which grows only in the Sedelberg Mountains of South Africa, and is available from this region. There are no particular restrictions on the constituent parts of Asparagus lineias used as the raw material for extraction, and examples include leaf parts, branch parts, trunk parts, bark parts, root parts, or a mixture of these parts. is there. In addition, the dried material of the leaf part of Asparasa linenalice is widely used as tea leaves of Rooibos tea.

  Gaiyou (name of crude drug) is a leaf part of artemisia (Artemisia priceps Pampanini), a perennial herb belonging to the genus Artemisia, which is distributed throughout Japan, and can be easily obtained from these regions. Conventionally, gaiyo has been used for hemostasis in the gynecological field, prevention of miscarriage and prevention of cold abdominal pain.

  Oolong tea is tea (scientific name: Camellia sinensis) leaves that are semi-fermented. Cha (Camellia sinensis) is an evergreen small shrub belonging to the genus Camellia that is distributed in China, India, Japan, etc., and can be easily obtained from these areas.

  Inchinkou (name of herbal medicine) is a flower part of the genus Artemisia capillaris belonging to the genus Artemisia capillaris which is a perennial plant distributed in Hokkaido, Honshu, Shikoku, Kyushu, etc., and is easily obtained from these areas be able to. Inchinkou has been conventionally used as a treatment for jaundice, a tonic, and the like.

  Ogon (herbal medicine) is the root part of the perennial grass, Scutellaria baicalensis Georgi, belonging to the genus Lamiaceae that is distributed in northern China, northeastern part, Mongolia, etc., and is easily obtained from these regions be able to. Ougon is conventionally used as a stomachic medicine, an antiallergic agent and the like.

  Arnica (scientific name: Arnica montana L.) is a perennial plant belonging to the genus Rabbitaceae that resembles daisy that grows on acid soil meadows in mountainous regions from Europe to Southern Russia. Can be obtained. Arnica constituent parts that can be used as the raw material for extraction include, for example, trunk, above-ground parts, flower parts, root parts, whole grasses, etc., preferably flower parts.

  The term “flower” generally refers to the whole organ involved in sexual reproduction of a seed plant, and is composed of a flower leaf that is a leaf deformation and a flower axis that is a stem deformation. , Organs such as petals, oshibe, and heart skin. In the present embodiment, the “floral part” that can be used as the raw material for extraction includes, in addition to the total organs involved in sexual reproduction of seed plants, a part thereof, for example, flower leaves, flower coats (buds and corolla), corolla, Also includes petals.

  Rose rose (scientific name: Rosa centifolia) is a plant belonging to the genus Rosaceae that is widely cultivated in Asia from Europe and can be easily obtained from these regions. Examples of the constituent parts of the rose that can be used as an extraction raw material include a flower part, a leaf part, a stem part, and the like, and a flower part is preferable.

  Ginkgo (scientific name: Ginkgo biloba L.) is a deciduous tree belonging to the genus Ginkgo genus that grows naturally in Hokkaido, Honshu, Shikoku, Kyushu, etc., and can be easily obtained from these regions. Examples of the constituent parts of ginkgo biloba used as an extraction raw material include leaf parts, flower parts, root parts, bark parts, branch parts, or a mixture of these parts, with the leaf part being preferred.

  Zhuyak (scientific name: Houttuynia cordata Thunberg) is a perennial herb belonging to the genus Dokudami, which is abundant in the Japanese marsh, and can be easily obtained from these areas. Examples of the constituent parts of zelkova that can be used as an extraction raw material include, for example, leaf parts, branch parts, bark parts, trunk parts, stem parts, fruit parts, seed parts, flower parts and the like, rhizome parts, or a mixture of these parts. The above-mentioned part is preferable.

  Biwa (scientific name: Eriobotrya japonica Lindley) is an evergreen tree belonging to the genus Biwa of the family Rosaceae, native to the southwestern part of China, and cultivated in Nagasaki, Chiba, Kagoshima, etc., and can be easily obtained from these areas it can. Examples of the part that can be used as the extraction raw material include a leaf part, a trunk part, a branch part, a flower part, a fruit part, a seed part, a root part, or a mixture of these parts, and a leaf part is preferable. The loquat of loquat is listed in the “Special Medical Supplement” and has long been used as a medicinal herb. It is said that the name is given because the shape of the leaf resembles a camellia. In Japan, in the Edo period, the decoction that was made by removing the loquat leaves and drying them was called “Yakuyaku-yu” and was used to remove heat.

  Hops (scientific name: Humulus lupulus) are perennials belonging to the genus Coleaceae that are widely cultivated in Europe, North America and the like, and can be easily obtained from these regions. Examples of the constituent parts of hops that can be used as an extraction raw material include leaf parts, root parts, flower parts, stem parts, female flower parts, or a mixture of these parts, but female flower parts are preferred.

  Asenyak (scientific name: Uncarina gambir) is a plant belonging to the Rubiaceae family that is distributed in Southeast Asia and the like, and is easily available from these regions. Examples of the constituent parts of Acacia catechu used as an extraction raw material include a flower (bud) part, a leaf part, a branch part, a bark part, a root part, and the like, and a leaf part is preferable.

  Achacha (scientific name: Hydrangea serrata) is a deciduous small shrub belonging to the genus Hydrangea hydrangea growing in the west of the Kanto region, Shikoku, Kyushu, etc., and can be easily obtained from these regions. Examples of the constituent parts of the armature that can be used as the raw material for extraction include leaf parts, stem parts, flower parts, cocoon parts, fruit parts, fruit core parts, above-ground parts, or a mixture of these parts. It is the ground part.

  Nettle (scientific name: Urtica thubergiana) is a perennial herb belonging to the genus Nettle that is distributed in Honshu, Shikoku, Kyushu, the Korean Peninsula, etc. in Japan, and can be easily obtained from these regions. Examples of the constituent parts of nettle that can be used as an extraction raw material include leaf parts, stem parts, flower parts, root parts, root bark parts, above-ground parts, whole grasses, or a mixture of these parts, preferably leaves. Part.

  Extracts from one or more plants selected from the group consisting of Japanese maple, Asparagus serie Alice, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rose of rose, Ginkgo, Jujuk, Biwa, Hop, Asenya, Sweet tea and Nettle Although the details of the substance having an inhibitory action on melanin uptake contained in potato are unknown, extracts having an inhibitory action on melanin uptake can be obtained from these plants by an extraction method generally used for extraction of plants. .

  The above extract can be obtained by drying the raw material for extraction and then pulverizing the raw material as it is or using a crusher and subjecting it to extraction with an extraction solvent. Drying may be performed in the sun or using a commonly used dryer. Moreover, after performing pretreatment, such as degreasing, with a nonpolar solvent such as hexane, it may be used as an extraction raw material. By performing pretreatment such as degreasing, extraction treatment with a polar solvent of a plant can be performed efficiently.

  As the extraction solvent, it is preferable to use a polar solvent, and examples thereof include water and hydrophilic organic solvents. These are used alone or in combination of two or more at room temperature or a temperature below the boiling point of the solvent. Is preferred.

  Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, and those subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, and the like. Therefore, the water that can be used as the extraction solvent in this embodiment includes purified water, hot water, ion exchange water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  Examples of hydrophilic organic solvents that can be used as extraction solvents include lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene. Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycol, propylene glycol and glycerin.

  When using the liquid mixture of 2 or more types of polar solvents as an extraction solvent, the mixing ratio can be adjusted suitably. For example, when using a mixed solution of water and a lower aliphatic alcohol, it is preferable to mix 1 to 90 parts by volume of a lower aliphatic alcohol with respect to 10 parts by volume of water. When using a mixed solution, it is preferable to mix 1 to 40 parts by volume of a lower aliphatic ketone with 10 parts by volume of water, and when using a mixed solution of water and a polyhydric alcohol, water 10 It is preferable to mix 10 to 90 parts by volume of a polyhydric alcohol with respect to the volume part.

  The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent 5 to 15 times (mass ratio) of the extraction raw material, the soluble components are extracted at room temperature or under reflux, and then filtered to remove the extraction residue. A liquid can be obtained. When the solvent is distilled off from the obtained extract, a paste-like concentrate is obtained, and when this concentrate is further dried, a dried product is obtained.

  Purification can be performed by, for example, activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like. From one or two or more plants selected from the group consisting of the obtained Japanese maple, asparagus serie alice, mussel, oolong tea, inchinkou, dragonfly, arnica, rose, ginkgo, jujube, loquat, hops, asenyaku, sweet tea and nettle Although this extract can be used as it is as an active ingredient of the melanin uptake inhibitor, a concentrated solution or a dried product is easier to use.

  Extracts from one or more plants selected from the group consisting of Japanese maple, Asparagus serie Alice, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rose of rose, Ginkgo, Jujuk, Biwa, Hop, Asenya, Sweet tea and Nettle Since it has a unique odor, it can be purified for the purpose of decolorization, deodorization, etc. within a range that does not cause a decrease in its physiological activity. Therefore, there is no practical problem even if it is not purified.

  1 type or 2 selected from the group consisting of Acer palmatum, Asparagus Linea Alice, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rose, Ginkgo, Jujube, Biwa, Hop, Asenya, Sweet tea and Nettle, obtained as described above Since the extract from the plant of a seed | species or more has a melanin uptake inhibitory action, it can be used as an active ingredient of a melanin uptake inhibitor using the action.

  The melanin uptake inhibitor of the present embodiment is 1 selected from the group consisting of Japanese maple, Asparasaslinearias, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rosewood, Ginkgo, Jujuk, Biwa, Hop, Asenyaku, Sweet tea and Nettle. It may consist only of extracts from seeds or two or more plants, or may be a formulation of the above extract.

  In the melanin uptake inhibitor of this embodiment, 1 selected from the group consisting of Acer palmatum, Asparasaslinearias, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rose, Ginkgo, Jujuk, Biwa, Hop, Asenyaku, Amacha and Nettle Content of the extract from a seed | species or 2 or more types of plants can be suitably set according to the objective. Moreover, when using 2 or more types of the said extract as an active ingredient, those compounding ratios should just adjust suitably according to the grade of the melanin uptake inhibitory action which those extracts have.

  Extracts from one or more plants selected from the group consisting of Japanese maple, Asparagus serie Alice, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rose of rose, Ginkgo, Jujuk, Biwa, Hop, Asenya, Sweet tea and Nettle Can be formulated into an arbitrary dosage form such as powder, granule, liquid and the like using a pharmaceutically acceptable carrier such as dextrin and cyclodextrin and any other auxiliary agent according to a conventional method. In this case, as an auxiliary agent, for example, an excipient, a stabilizer, a flavoring / flavoring agent, and the like can be used. Examples of the form of the melanin uptake inhibitor obtained by formulating the extract include ointments, external liquids, patches and the like.

  In addition, the melanin uptake inhibitor of the present embodiment, if necessary, other natural extracts having a melanin uptake inhibitory action, such as Japanese maple, asparasaslinearias, gayyo, oolong tea, Inchinkou, Ogon, Arnica, Seiyo It can be blended with an extract from one or more plants selected from the group consisting of rose, ginkgo, jujube, loquat, hop, asenya, sweet tea and nettle and used as an active ingredient.

  Examples of the method for administering the melanin uptake inhibitor of the present embodiment to a patient include subcutaneous tissue administration, intravenous administration, transdermal administration, and the like, but it is suitable for its prevention and treatment depending on the type of disease. A method may be selected as appropriate. In addition, the dosage of the melanin uptake inhibitor of this embodiment may be appropriately increased or decreased depending on the type of disease, severity, individual differences among patients, administration method, administration period, and the like.

  The melanin uptake inhibitor of the present embodiment is 1 selected from the group consisting of Japanese maple, Asparasaslinearias, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rosewood, Ginkgo, Jujuk, Biwa, Hop, Asenyaku, Sweet tea and Nettle. Through the melanin uptake-inhibiting action of seeds or extracts from two or more kinds of plants, the uptake of melanin (melanosomes) by phagocytosis (phagocytosis) of epidermal cells (keratinocytes) can be suppressed, thereby the skin Can prevent, treat or ameliorate the darkness (skin pigmentation), spots, buckwheat, and the like. However, the melanin uptake inhibitor of the present embodiment can be used for all purposes that are meaningful for exhibiting an action of inhibiting melanin uptake other than these uses.

  In addition, although the melanin uptake inhibitor of this embodiment is suitably applied to humans, it can also be applied to animals other than humans as long as each effect is exhibited.

  Hereinafter, although a test example is shown and this invention is demonstrated concretely, this invention is not restrict | limited to each following example at all. In the following test examples, lyophilized products (samples 1 to 15) shown in Table 1 were used as samples.

[Test Example 1] Melanin uptake inhibitory action test The above plant extracts (Samples 1 to 15) were tested for melanin uptake inhibitory action as follows.

Human normal neonatal skin epidermal keratinocytes (NHEK) were cultured using human normal neonatal epidermal keratinocyte medium (KGM), and then cells were collected by trypsin treatment. The collected cells were diluted with KGM to a cell density of 2 × 10 ⁵ cells / mL, and then 100 μL each was seeded on a collagen-coated 96-well plate and cultured overnight.

After completion of the culture, the medium was removed, and 100 μL of a sample solution dissolved in KGM (samples 1 to 15; see Table 2 below for the sample concentration) was added to each well and cultured for 24 hours. After completion of the culture, red fluorescent beads (particle size: 1.0 μm, Fluorescent Microspheres, 580/605 nm; manufactured by Molecular Probes) as pseudo melanin were added to a concentration of 3.6 × 10 ⁷ cells / mL. 100 μL of% BSA-containing KGM was added to each well and incubated for 4 hours.

  After completion of the culture, the medium was removed, washed with ice-cooled KGM and PBS, and 100 μL of PBS was added to each well, and the amount of fluorescence was measured. From the obtained measurement results, the melanin uptake inhibition rate (%) was calculated by the following formula.

Melanin uptake inhibition rate (%) = (1−A / B) × 100
In the formula, A represents “fluorescence amount at the time of sample addition”, and B represents “fluorescence amount at the time of no sample addition”.
The results are shown in Table 2.

  As shown in Table 2, all the extracts from Japanese maple, asparagus linen alice, gaiyo, oolong tea, ginseng, dragonfly, arnica, rose, ginkgo, jujube, loquat, hop, asenyaku, sweet tea and nettle are all incorporated with melanin. It was confirmed to have an inhibitory action.

  Among these, the extracts from Japanese maple, Asparagus linen alice, gayyo, oolong tea, Inchinkou, Ogon, Arnica and Asenyaku have an excellent melanin uptake inhibitory action, Oolong tea and asenyaku were found to have an extremely excellent melanin uptake inhibitory effect.

  The melanin uptake inhibitor of the present invention can greatly contribute to the prevention, treatment or improvement of skin darkness (skin pigmentation), spots, buckwheat and the like.

Claims (1)

  Extracts from one or more plants selected from the group consisting of Japanese maple, Asparagus serie Alice, Guillain, Oolong tea, Inchinkou, Ogon, Arnica, Rose of rose, Ginkgo, Jujuk, Biwa, Hop, Asenya, Sweet tea and Nettle A melanin uptake inhibitor characterized by comprising