JP6773362B2 - Skin moisturizer for ingestion or administration - Google Patents

Description

The present invention relates to a skin moisturizer that exerts a moisturizing effect on the skin when orally ingested or administered by humans or other animals.

The skin is composed of the epidermis and the dermis. One of the functions of the epidermis is a water retention function that prevents water from escaping from the body. On the other hand, the dermis has few cells and is mainly composed of extracellular matrix and water. The extracellular matrix is composed of protein fibers such as collagen fibers and elastin fibers that are involved in skin tension and elasticity, and substrates of proteoglycans (hyaluronic acid, dermatan sulfate, chondroitin sulfate, etc.) that are important for maintaining water retention. One of the cells contained in the dermis is fibroblast, which synthesizes extracellular matrix components, and the activity state of fibroblast has an important influence on cell tension and elasticity.

Skin aging includes phenomena such as wrinkles, age spots, and tarmi on the skin, which become more prominent with aging.
According to Non-Patent Document 1, there are external factors and internal factors as causes of aging, ultraviolet rays, oxidation, and dryness are mentioned as external factors that promote skin aging, and females are internal factors. These include decreased hormones, decreased blood flow, and mental stress. These factors are involved and cause skin aging.

There are many known causes of dry skin, and Non-Patent Document 1 lists the following causes.

(Reduction of the sebum layer of the epidermis) The sebum film has the role of retaining water in the skin and preventing evaporation. When the sebaceous membrane decreases with age, the skin becomes dry.

(Increased barrier function due to decreased turnover of epidermal cells) The stratum corneum below the sebum layer is composed of keratinocyte-derived stratum corneum and intercellular lipids (ceramide, cholesterol, fatty acids). The epidermis becomes thinner as the proliferation of keratinocytes decreases with age. On the other hand, with aging, the turnover time of cells is prolonged, the stratum corneum becomes thicker, the amount of water lost from the body through the epidermis decreases, and the barrier function rather increases. As a result, in the elderly, the barrier function of the skin is enhanced, and when the skin surface is dried due to the drying of the outside air, the hydration from the body to the stratum corneum via the epidermis is small, and the drying of the skin cannot be stopped. ..

(Decrease in the amount of ceramide in the epidermis) When the amount of ceramide decreases with age, the amount of keratin water decreases, leading to dryness and decreased flexibility of the skin.

(Reduction of NMF in the epidermis) With aging, the amount of amino acids derived from the decomposition of filaggrin, which is a precursor of NMF (Natural Moisturizing Factor), decreases, and the moisturizing function of the stratum corneum is impaired, resulting in dry skin. And leads to reduced flexibility.

(Reduction in extracellular matrix amount in the dermis) In the dermis, the proliferative capacity of fibroblasts that produce extracellular matrix decreases, the amount of extracellular matrix also decreases, and tissue metabolism slows down with aging. The tension and elasticity of the skin is lost, water retention is lost, and dryness occurs.

In addition, Non-Patent Document 2 cites a decrease in the expression level of aquaporin 3 in epidermal cells associated with aging and sunburn as a cause of dry skin. Aquaporins, including aquaporin 3, are proteins that are present in the cell membrane of epidermal cells and function as water channels.

In Non-Patent Document 1, a plurality of types of existing techniques for preventing dry skin are listed.
(1) Ingest beauty foods containing ceramide, water-soluble amino acids, etc., which are components of the epidermis.
(2) Ingest beauty foods containing extracellular matrix such as collagen, hyaluronic acid, and chondroitin sulfate, which are components of the dermis.
(3) For epidermal keratinocytes contained in the epidermis, a skin cell activating material or a skin cell metabolism activating material having a growth promoting effect, a keratinizing normalizing effect, a ceramide synthesis promoting effect, a fibrin synthesis promoting effect, etc. Ingest.
(4) A skin cell activating material or a skin cell metabolism activating material having a growth promoting action, a collagen synthesis promoting action, a hyaluronic acid synthesis promoting action, a collagen degrading enzyme inhibitory action, etc. on the skin fibroblasts contained in the dermis. Ingest.

On the other hand, turmeric (Curcuma longa LINNE) in the center of Southeast Asia, is the ginger family turmeric species of medicinal plants that are grown in tropical and subtropical regions of the world. Patent Documents 1 to 9 propose a technique for improving the condition of the skin by orally ingesting an extract of a site such as a rhizome of turmeric as described below.

Patent Document 1 discloses a dermal fibroblast activator containing an extract of a plant selected from plants of the genus Turmeric of the family Zingiberaceae.

Patent Document 2 discloses an ATP production promoter and an epidermal cell activator containing an extract of a plant such as turmeric as an active ingredient. According to Patent Document 2, a decrease in the moisturizing function and elasticity of the skin causes a delay in the epidermal turnover rate due to a decrease in the activity of epidermal cells of the skin and a decrease in the ability to divide, which causes differentiation failure such as thinning of the skin and thickening of the stratum corneum. Recognizing that this is caused by this, ATP production promoters and epidermal cell activators are provided.

Patent Document 3 discloses a mucopolysaccharide fragmentation inhibitor containing an extract extracted from a plant such as turmeric with water or a lower alcohol or a lower alcohol aqueous solution as an active ingredient. Mucopolysaccharides include hyaluronic acid, chondroitin, chondroitin sulfate, dermatan sulfate and the like. It is described in Patent Document 3 that mucopolysaccharide is a main component in the dermis of the skin, and fragmentation by active oxygen and ultraviolet rays leads to aging of the skin.

Patent Document 4 discloses a skin-activating food containing water or an aqueous alcohol extract as an active ingredient of a crude drug mixture consisting of auction, sanshin, ginger, kouka, turmeric and yokuinin. In Patent Document 4, it has been confirmed that humans actually ingest the above foods orally to improve rough skin, age spots, and itching.

Patent Document 5 discloses an anti-aging agent containing an extract of fermented turmeric. The anti-aging agent of Patent Document 5 has a skin fibroblast growth promoting action, a transglutaminase-1 production promoting action, an elastase activity inhibiting action, an MMP-1 activity inhibiting action, an estrogen-like action, a type I collagen production promoting action, and epidermal keratinization. It has at least one of a cell proliferation promoting action and a recovery action from UV-B damage.

Patent Document 6 discloses a whitening agent, an antioxidant, an external preparation for skin, and a functional oral composition containing an extract of the bud of the rhizome of a plant belonging to the genus Curcuma of the family Zingiberaceae as an active ingredient.

Patent Document 7 discloses an NF-κB activation inhibitor containing an extract of turmeric. According to Patent Document 7, the NF-κB activation inhibitor has effects such as exfoliation, thickening, rough skin, disordered texture, pigmentation, degeneration / destruction of dermis constituents, and prevention / improvement of itching. It is said to be useful for the prevention and improvement of symptoms associated with the physiological aging of the skin and photoaging.

Patent Document 8 discloses an elastase activity inhibitor containing a turmeric extract. The invention of Patent Document 8 aims to prevent skin aging and maintain youthful skin without wrinkles and tarmi by suppressing the activity of elastase and recovering / maintaining the firmness and elasticity of the skin. And.

In Patent Document 9, an extract of Curcuma longa is described as an example of an anti-wrinkle agent and / or an anti-aging agent.

In Patent Documents 1 to 3 and 5 to 9, the composition containing the turmeric-derived material specified in each document may be in the form of food or drink taken orally as well as in the form of external application to the skin such as cosmetics. However, it has not been confirmed that the desired effect can be achieved by actually ingesting it orally.

Japanese Unexamined Patent Publication No. 2004-75632 JP-A-2009-256272 Japanese Unexamined Patent Publication No. 6-24937 JP-A-59-106277 JP-A-2009-242263 Japanese Unexamined Patent Publication No. 2011-246375 Japanese Unexamined Patent Publication No. 2005-192246 JP-A-2002-205950 Special Table 2013-533226

Benefits and prospects of beauty foods, CMC Publishing, supervised by Takeshi Inoi Evaluation and development of skin-beautifying food materials, CMC Publishing, supervised by Tetsuro Yamamoto

As described in Non-Patent Document 1, since dry skin is one of the causes of skin aging (wrinkles, age spots, tarmi, etc.), skin aging can be suppressed by increasing or retaining the water content of the skin. there is a possibility. Therefore, there is a need for a means capable of increasing or retaining the water content of the skin by oral ingestion (note that in the present specification, increasing or retaining the water content of the skin is defined as the skin moisture. Moisturizing. Here, "retention" of water includes suppressing the decrease of water).

However, as described above, dry skin is caused by various factors in the epidermis and dermis, and is not caused by only one specific cause. Therefore, it is easy to provide a means for realizing moisturizing of the skin. It's not that. In Non-Patent Document 1, the above four types are listed as means for preventing dry skin by oral ingestion, but even if only one of the various factors that cause dry skin is removed, dry skin can be prevented. It cannot be prevented.

The compositions containing turmeric-derived components described in Patent Documents 1 to 5, 7 and 8 are not intended to moisturize the skin. These compositions have an action similar to any of the above types described in Non-Patent Document 1, but only individually eliminate some of the various factors that cause dry skin and moisturize the skin. It is completely unpredictable whether it can be achieved.

Patent Document 6 describes that the extract of the rhizome of a plant belonging to the genus Turmeric of the family Zingiberaceae has a whitening effect and an antioxidant effect, and Patent Document 9 describes that the extract of Curcuma longa is an anti-wrinkle agent and / or anti-anti-wrinkle agent. It is described as useful as an aging agent. However, as described in Non-Patent Document 1, skin aging is caused by external factors such as ultraviolet rays, oxidation, and dryness, and internal factors such as decrease in female hormones, decrease in blood flow, and mental stress. It is unclear whether the whitening action and anti-wrinkle action, that is, the anti-aging action, of the compositions described in Patent Documents 6 and 9 are realized through moisturizing the skin.

The present invention is a problem to be solved to provide a new means capable of moisturizing the skin by ingestion or administration.

The present inventors have found that the following methods are effective as means for solving the above problems, and have completed the present invention.
(1) A skin moisturizer for oral ingestion or administration, which comprises a turmeric extract.
(2) The skin moisturizer for oral ingestion or administration of (1), wherein the turmeric extract contains Bisacurone.
(3) A skin moisturizer for oral ingestion or administration, which comprises bisacron.

The skin moisturizer for oral ingestion of the present invention can moisturize the skin by oral ingestion or oral administration.

The measurement results of the skin water content on the 3rd and 4th days after UV-B irradiation between the group of hairless mice ingesting the turmeric extract containing Bisacurone and the control group are shown. The skin water content is indicated by the average value ± standard deviation value with the skin water content of each group before UV-B irradiation as 100. * Indicates that p <0.05 is significantly higher than that of the control group.

Hereinafter, the present invention will be described in detail.
The skin moisturizer of the present invention is characterized by containing at least a turmeric extract or Bisacurone.
The skin moisturizer of the present invention may contain components other than turmeric extract or bisacron.
The skin moisturizer of the present invention comprises, in one embodiment, a turmeric extract or bisacurone.
The skin moisturizer of the present invention can be formulated as a skin moisturizer composition together with at least one other component.

In the present invention, "containing" includes a mixed state or a coexisting state. The coexisting state means a state in which each is separated before use, but is in a coexisting combination state, and is mixed and used at the time of use.

<Turmeric extract>
In the present invention, the turmeric extract refers to an extract (turmeric extract) of a plant material derived from a plant of the genus Turmeric of the family Zingiberaceae, which is further heated and / or reduced in pressure as necessary to volatilize the extraction solvent. , May be dried. These heating, depressurizing, and drying methods are not particularly limited, and for example, conventionally known methods can be used.

Examples of the plant raw material include Curcuma longa (turmeric), Curcuma aromatica, Curcuma zedoraia, Curcuma phaeocalis, Curcuma kwangsiensis, Curcuma roots, Curcuma stalks, Curcuma stalks, etc. These rhizomes may be collected from the soil, and the appropriate part of the rhizome may be cut into the original shape, cut to an appropriate size or shape, or crushed. it can. These plant raw materials may be appropriately dried. The plant material is preferably not fermented.

The method for extracting the turmeric extract from the plant material is not particularly limited, and a conventionally known method can be used. The extraction solvent is preferably at least one selected from the group consisting of water and an organic solvent (may be a mixed solvent of two or more kinds of solvents). As the organic solvent, a hydrophobic organic solvent such as hexane or a hydrophilic organic solvent such as alcohol or acetone can be used. The extraction solvent is preferably at least one selected from the group consisting of water and a hydrophilic organic solvent, and water, a hydrophilic organic solvent, a mixed solvent of water and a hydrophilic organic solvent, and the like are particularly preferable. The hydrophilic organic solvent may be a mixed solvent of a plurality of types of hydrophilic organic solvents. The temperature of "water" is not particularly limited and includes hot water. The hydrophilic organic solvent is preferably at least one alcohol (may be a mixed solvent of a plurality of alcohols), and the alcohol is not particularly limited, but ethanol is preferable.

In the present invention, when a mixed solvent of a hydrophilic organic solvent and water is used, the mixing ratio is not particularly limited, but for example, the weight ratio is preferably in the range of 10:90 to 90:10, and 20:80 to 50:50. The range of is more preferable. The temperature at the time of extraction is not particularly limited.

The turmeric extract extracted using at least one selected from the group consisting of water and a hydrophilic organic solvent as the extraction solvent is a turmeric extract extracted using a hydrophobic organic solvent such as ethyl acetate as the extraction solvent. It contains a compound having a higher water solubility than the product. Therefore, these extracts are clearly different from each other in the composition of the components contained.

In the present invention, a turmeric extract extracted using at least one selected from the group consisting of water and a hydrophilic organic solvent as an extraction solvent may be referred to as a "water-soluble turmeric extract".

In the present invention, as the turmeric extract, the turmeric rhizome extract obtained as described above can be used as it is, and the turmeric rhizome extract is further diluted, concentrated, dried or the like. It is also possible to use the one with the above. Conventionally known methods can be used as methods such as dilution, concentration, and drying.

The turmeric extract used in the present invention is preferably characterized by containing Bisacurone. Bisacurone is preferably contained in an amount of 0.1% by weight or more, preferably 0.15% by weight or more, based on the total amount of the turmeric extract. The amount of Bisacurone in the turmeric extract is a high-performance liquid that is obtained by mixing the turmeric extract with ethyl acetate, distilling off ethyl acetate from the supernatant obtained by centrifugation under reduced pressure, and then dissolving the solution in acetonitrile as an analysis sample. It can be determined by subjecting to chromatography (HPLC).

In the present invention, bisaclone is a compound classified into bisabolan-type sesquiterpenes, and means a compound having the following planar structural formula or a salt thereof. Bisacurone has an asymmetric carbon at the position marked with * in the planar structural formula, and therefore there are several types of optical isomers. Bisacurone in the present specification is a concept that includes any of these optical isomers. is there.

The turmeric extract used in the present invention preferably has a curcumin content of 0.5% by weight or less, and more preferably does not contain curcumin.

The skin moisturizer of the present invention may contain bisacron as an active ingredient. Bisacurone may be separated from the turmeric extract and purified if necessary. Bisacurone may also be isolated from natural materials other than turmeric or artificially synthesized.

The turmeric extract used in the present invention is preferably not an extract of a crude drug mixture consisting of auction, sanshin, ginger, turmeric, turmeric, and yokuinin.

<Skin moisturizer for oral ingestion or administration>
The skin moisturizer for oral ingestion or administration of the present invention is intended for humans or animals, and has an action of maintaining the water content of the skin in the subject and / or an action of suppressing a decrease in the water content by oral ingestion or oral administration. Have. Here, "oral ingestion" means that the subject voluntarily takes it into the body by an oral route, and "oral administration" means that if the subject is a human, the subject is an animal at the will of a doctor or the like. In the case, it refers to taking it into the body by the oral route at the will of the breeder or veterinarian. Hereinafter, "skin moisturizer for oral ingestion or administration" may be simply referred to as "skin moisturizer".

The skin moisturizer of the present invention is effective for moisturizing the skin, especially in the epidermis. Therefore, the skin moisturizer of the present invention is more preferably an epidermal moisturizer for oral ingestion or administration.

The skin moisturizer of the present invention is effective for moisturizing the skin after being irradiated with UV rays due to sunburn or the like. Therefore, the skin moisturizer of the present invention is more preferably a skin moisturizer for oral ingestion or administration for the skin after UV irradiation (preferably after sunburn).

In the embodiment in which the skin moisturizer of the present invention contains a turmeric extract, the content of the turmeric extract in the skin moisturizer is not particularly limited.

In the embodiment in which the skin moisturizer of the present invention contains a turmeric extract containing Bisacurone, the content of the turmeric extract in the skin moisturizer is not particularly limited, but for example, the subject 1 of the skin moisturizer of the present invention. The amount of bisacron is preferably 0.01 to 30 mg, more preferably 0.1 to 3 mg per daily oral intake or oral dose per individual (preferably one adult when the subject is human). is there. The skin moisturizer of the present invention contains a turmeric extract in an amount such that the daily oral intake or oral dose per 1 kg of the body weight of the subject is preferably 0.17 μg to 500 μg, more preferably 2.5 μg to 50 μg as bisaclone. contains.

In the embodiment in which the skin moisturizer of the present invention contains bisacurone, the content of bisacurone in the skin moisturizer is not particularly limited, but for example, one subject of the skin moisturizer of the present invention (when the target is a human). Bisacurone is 0.01 to 30 mg, more preferably 0.1 to 3 mg, per daily oral intake or oral dose per adult). The skin moisturizer of the present invention contains bisacron in an amount such that the daily oral intake or oral dose per 1 kg of the body weight of the subject is preferably 0.17 μg to 500 μg, more preferably 2.5 μg to 50 μg.

Here, "daily oral intake or oral dose per subject of the skin moisturizer of the present invention" means 0.1 g as the amount of the composition in which the skin moisturizer of the present invention is combined with other components. It is ~ 500 g, preferably in the form of a beverage composition, preferably 50-500 g or 50-500 mL, most preferably 90-200 g or 90-200 mL. The skin moisturizer of the present invention may be continuously ingested or administered, or may be ingested or administered when necessary.

The skin moisturizer of the present invention may be ingested or administered as it is, or may be ingested or administered in the form of various compositions obtained by formulation with at least one other component.

Oral ingestion or administration of the skin moisturizing agent of the present invention can increase the water content of the skin and improve the moist state of the skin.

The skin moisturizer of the present invention also retains the water content of the skin by oral ingestion or administration, enabling maintenance of skin homeostasis, prevention of disorders, and improvement of disorders.

<Formulation>
The composition in which the skin moisturizing agent of the present invention is formulated together with at least one other component is a composition having the above-mentioned skin moisturizing effect by oral ingestion or oral administration, and more preferably a skin moisturizing composition. ..

The composition further contains one or more components other than the skin moisturizer of the present invention. The composition is not particularly limited, but preferably, a composition which is ingested or administered by an oral route such as a pharmaceutical product (for humans or animals), food and drink, feed, food additive, feed additive and the like can be mentioned. ..

Other ingredients include, for example, other plant extracts, vitamins, dietary fiber, high fructose corn syrup, dextrin, acidulants, thickeners, turmeric pigments, inositol, fragrances, cyclic oligosaccharides, sweeteners, minerals, etc. Examples include antioxidants, emulsifiers, water and the like.

Examples of other plant extracts include hawthorn extract, safflower extract, yurine extract and the like.

Examples of vitamins include niacin, vitamin B1, vitamin B2, vitamin B6, vitamin C, vitamin E and the like.

Examples of the acidulant include citric acid, malic acid, gluconic acid, tartaric acid, and salts thereof.

Examples of the thickener include thickening polysaccharides such as gellan gum, xanthan gum, pectin, and guar gum.

The turmeric pigment is obtained by extracting from the rhizome portion of turmeric with warm ethanol, hot fat or propylene glycol, or room temperature to hot hexane or acetone, and it is preferable that it mainly contains curcumin. .. The amount of turmeric pigment in the composition is about 3 mg to 50 mg, more preferably about 5 mg to 40 mg, and particularly preferably about 6 mg to 30 mg of curcumin per daily oral ingestion or oral dose per subject. It is recommended that an amount of turmeric pigment be added.

Examples of minerals include magnesium, calcium, sodium and potassium.

Examples of the antioxidant include vitamin C, enzyme-treated rutin and the like.
Examples of the sweetener include sugars such as fructose, glucose and liquid sugar, and high-sweetness sweeteners such as honey, sucralose, acesulfame potassium, thaumatin and aspartame.

The shape of the composition for oral ingestion or oral administration in which the skin moisturizer of the present invention is formulated with at least one other component is not particularly limited as long as it is suitable for the oral route, and is liquid or semi-solid. Various forms such as a shape (gel state, etc.) and a solid state can be mentioned.

When the composition is a food or drink, the shape of a general food or drink such as a beverage, a confectionery (for example, gum, candy, caramel, chocolate, cookie, snack confectionery, jelly, gummy, tablet confectionery, etc.), a supplement, etc. It can be the shape of a dietary supplement. The shape of the supplement may be, for example, tablet-like, round, capsule (including hard capsule, soft capsule, microcapsule), powder, granule, fine granule, troche, liquid (syrup, milky, suspension). Including) and the like. These can be manufactured according to a conventional method.

In the embodiment in which the skin moisturizer of the present invention contains a turmeric extract, the content of the turmeric extract in the composition containing the turmeric extract is not particularly limited.

In the embodiment in which the skin moisturizer of the present invention contains a turmeric extract containing Bisacurone, the content of the turmeric extract in the composition containing the turmeric extract is not particularly limited, but for example, the subject 1 of the composition. The amount is 0.01 to 30 mg, more preferably 0.15 to 3 mg of bisacron per daily oral intake or oral dose per individual (preferably one adult when the subject is human). The composition contains an amount of turmeric extract such that the daily oral ingestion or oral dose per 1 kg of the body weight of the subject is preferably 0.17 μg to 500 μg, more preferably 2.5 μg to 50 μg as bisaclone.

In the embodiment in which the skin moisturizer of the present invention contains bisacurone, the content of bisacurone in the composition containing the bisacurone is not particularly limited, but for example, one target individual of the composition (when the target is a human). Bisacurone is 0.01 to 30 mg, more preferably 0.1 to 3 mg, per daily oral intake or oral dose per adult). The composition contains bisacron in an amount such that the daily oral ingestion or oral dose per 1 kg of body weight of the subject is preferably 0.17 μg to 500 μg, more preferably 2.5 μg to 50 μg.

Here, the "daily oral intake or oral dose per subject of the composition" is 0.1 g to 500 g, and is preferably 50 to 500 g or 50 to 500 mL in the form of a beverage composition. Most preferably 90-200 g or 90-200 mL. The composition may be continuously ingested or administered, or may be ingested or administered when necessary.

<Evaluation of moisturizing effect>
After acclimatizing the hairless mouse Hos: HR-1 mouse (male, 5 weeks old, Nippon SLC Co., Ltd.) for 41 days, 0.05 weight was added to AIN-93G (EPS Masshin Co., Ltd.) as a test meal. The turmeric extract-blended diet and water obtained by blending% turmeric extract were freely fed for 19 days. The control group was allowed to freely feed AIN-93G and water. The turmeric extract feeding group consisted of 11 mice, and the control group consisted of 12 mice.

The turmeric extract, from rhizome part of turmeric (Zingiberaceae turmeric, Curcuma longa LINNE), is obtained by using water as the extraction solvent. The turmeric extract contains Bisacurone at a concentration of 0.15% by weight. Therefore, the turmeric extract-containing diet contains 0.000075% by weight of Bisacurone. The daily intake of one mouse was 50 mg / Kg body weight of turmeric extract and 75 μg / Kg body weight of Bisacurone.

(UV-B single irradiation)
On the 15th day after the start of eating the test meal, the back of the mouse was irradiated with UV-B (54 mJ / cm ² ) for 1 minute.

(Measurement of skin water content)
The skin water content before UV-B irradiation, 3 days after UV-B irradiation, and 4 days after UV-B irradiation was measured with the multi-probe adapter MPA5 and Corneometer (model number CM825MP, manufactured by Integral Corporation) as a measurement probe. Used and measured. The Corneometer can instantly measure the water content of about 15 μm (mainly the stratum corneum) from the skin surface by the principle of the capacitance method.

The measurement results of the skin moisture content on the 3rd day after the UV-B irradiation and the 4th day after the UV-B irradiation are shown in FIG. 1, assuming that the skin moisture content of each group before the UV-B irradiation is 100. On the 4th day after irradiation, the skin water content of the turmeric extract intake group was significantly higher than that of the control group (Fig. 1).

Claims (1)

Oral ingestion or administration comprising a water extract of turmeric (Curcuma longa LINE) , said extract containing bisacron, and a curcumin content in the extract of 0.5% by weight or less. For skin moisturizer.

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