JP5952256B2 - Beauty composition - Google Patents

Description

  The present invention is a cosmetic composition containing sphingolipid and saponarine, a composition for preventing and improving skin dryness, a composition for improving rough skin, a composition for suppressing skin moisture transpiration, a composition for moisturizing skin, a composition for improving skin barrier function, and a composition for suppressing skin itching. The present invention relates to a composition, a tight junction function enhancement composition, and a claudin-1 expression promoting composition.

The stratum corneum, which is the outermost layer of the skin, has the function of maintaining the skin's flexibility and appearance by keeping moisture in the stratum corneum while suppressing the ingress of substances from the outside and the evaporation of moisture from the inside of the skin. doing. In this stratum corneum, lipids called stratum corneum lipids are present so as to fill the gaps between the stratum corneum cells, and 50% of the stratum corneum lipids are known to be ceramide, a kind of sphingolipid. ing. In general, it is known that when the stratum corneum lipid (particularly ceramide) decreases from the stratum corneum, it causes rough skin, dry skin, aging skin and the like.
Conventionally, it is said that the state of the stratum corneum having a reduced function can be improved by supplementing externally applied sphingolipids such as ceramide with respect to the decrease in stratum corneum lipid from the stratum corneum.

  Examples of cosmetic use of sphingolipids include epidermal cell growth promoters and skin external preparations (Patent Document 1) containing glucosylceramide derived from salmon, and by dissolving sphingoglycolipids (β-glucosylceramide). Aqueous solution or emulsified aqueous solution (Patent Document 2) that exerts a barrier function or moisture retention (moisture transpiration protection) function to ensure skin moisture retention, ceramides such as ceramide, glucosylceramide, galactosylceramide and diisopropylamine dichloroacetate, or Although skin cosmetics (patent document 3) etc. which mix | blended (gamma) -aminobutyric acid etc. are disclosed, development of the composition with the more outstanding cosmetic effect and functionality was desired.

  Saponarine is a kind of flavonoid and has been conventionally known to be contained in plant flowers. Mucuge is known as a plant containing this saponarine, and the dried flower is used in Chinese medicine as a kiso flower. However, at present, saponarine itself is hardly used for cosmetic purposes.

On the other hand, tight junctions existing in the epidermis granule layer of the skin keep adjacent skins in close contact with each other and seal the gap between cells, thereby preventing moisture evaporation in the skin and permeating substances from the outside world. It is known that it can be controlled. Recent studies have shown that this tight junction plays an important role in the skin barrier function (Non-Patent Document 1).
Furthermore, it has been found that cell membrane proteins such as claudin constituting the tight junction control the barrier function of the tight junction by forming a strand (Non-patent Document 2).
Therefore, when the expression of cell membrane proteins such as claudin decreases, structural breakdown of the tight junction occurs, and the tight junction does not function as a barrier against the permeation of substances, so dry skin, rough skin, atopic dermatitis, It is considered that skin symptoms such as various infectious diseases and itching of the skin accompanying it are caused. (Patent Document 4)

As an agent for promoting the formation of tight junctions against the above-mentioned deterioration of skin symptoms, an external preparation for skin containing an extract of rhizome of Ranunculaceae genus Auren (patent document 5), pericarp of mandarin orange genus Daidai (spruce) An external preparation for skin containing an extract of (Patent Document 6) and the like are disclosed.
In addition, at least one selected from an extract of Arnica, an extract of Ashitaba, an extract of nematode, an extract of pearl barley, and an extract of Cordyceps as an ingredient that promotes the production of claudin, a cell membrane protein. The claudin-1 production promoter to contain etc. is disclosed (patent document 4).
However, some of the known claudin-1 (hereinafter referred to as CLDN1) production accelerators have a low production promotion rate of CLDN1, and are more excellent in the action of promoting the formation of tight junctions. Development of was desired.

JP 2011-195550 A JP 2013-155117 A Japanese Patent Laid-Open No. 01-22810 JP 2010-65007 A JP 2007-176830 A JP 2007-176835 A

TheJournal of Cell Biology 156: 1099-1111 (2002) Japanese Cosmetic Science Society Vol. 31: 296-301 (2007)

  The present invention is a cosmetic composition, a skin itch suppression composition, a skin dryness prevention / improvement composition, a skin roughness improvement composition, a skin moisture transpiration suppression composition, a skin moisturizing composition, a skin barrier function improving composition, and a tight junction function enhancement. It is an object of the present invention to provide a composition, a CLDN1 expression promoting composition (hereinafter referred to as the composition of the present invention).

The present inventors have conducted intensive studies in view of the above problems, and found that a composition containing sphingolipid and saponaline has an excellent effect in promoting the expression of CLND1 that works for the formation of tight junctions, leading to the present invention. It was.

The composition of the present invention is as follows.
(1) A cosmetic composition comprising sphingolipid and saponaline.
(2) A composition for preventing and improving skin dryness, comprising sphingolipid and saponaline.
(3) A rough skin improving composition comprising sphingolipid and saponaline.
(4) A skin moisture transpiration inhibiting composition comprising sphingolipid and saponaline.
(5) A skin moisturizing composition comprising a sphingolipid and saponin.
(6) A composition for improving skin barrier function, comprising sphingolipid and saponaline.
(7) A composition for suppressing skin itch, comprising sphingolipid and saponaline.
(8) A tight junction function-enhancing composition comprising sphingolipid and saponaline.
(9) A claudin-1 expression promoting composition comprising sphingolipid and saponaline.
(10) The composition according to any one of (1) to (9), wherein the sphingolipid is glucosylceramide in the composition of the present invention.

By the composition of the present invention, the expression of CLDN1 is promoted, the formation of tight junction can be promoted, the barrier function of the skin can be strengthened / improved, the skin moisturizing effect is enhanced, and the skin is dried. Can be prevented.
Thereby, it is possible to suppress / prevent skin itching, rough skin, etc. by preventing the skin from drying.

It is a figure which shows the expression rate of mRNA which codes CLDN1 of Example 1 thru | or 3, Comparative Examples 1 and 2.

  Hereinafter, the composition of the present invention will be described. In addition, this invention is not limited to the following embodiment.

The sphingolipid used in the present invention is a general term for complex lipids containing sphingoids (sphingoid bases), which are long-chain alcohols having amino groups. Specifically, the sphingoids are classified into ceramides in which fatty acids are acid-amide bonded, sphingoglycolipids in which sugars are bonded to the ceramides, and sphingophospholipids in which phosphoric acid and a base are bonded.
These sphingolipids are known to exist widely in the living world, and are used in various applications such as pharmaceutical applications as well as cosmetic applications for the purpose of improving the functional deterioration of the stratum corneum.
The sphingolipid in the present invention is represented by the following chemical formula.

(In the above general formula, R ¹ is a saturated or unsaturated long-chain hydrocarbon or long-chain alcohol having 15 to 19 carbon atoms, and R ² is a linear or branched acyl group having 12 to 28 carbon atoms ( R ³ represents hydrogen, a monosaccharide residue, an oligosaccharide residue, a phosphate group, a phosphocholine residue, a phosphoserine residue, a phosphoethanolamine residue, or a phosphoinositol residue.)

Ceramide is an amino group of sphingoids bonded with a linear or branched fatty acid having 12 to 28 carbon atoms. In (Chemical Formula 1), R ¹ is saturated or unsaturated having 15 to 19 carbon atoms. Long chain hydrocarbon or long chain alcohol, R ² is a linear or branched acyl group (fatty acid group) having 12 to 28 carbon atoms, and R ³ is hydrogen. Seven types of ceramide types 1 to 7 are generally known. The glycosphingolipid and sphingophospholipid described later have a common structure of ceramide.
Glycosphingolipids are those obtained by binding saccharides to the aforementioned ceramide. In (Chemical Formula 1), R ¹ and R ² are the same as ceramide, and R ³ is a monosaccharide residue or an oligosaccharide residue. Examples of the saccharide include glucose, mannose, galactose, fructose, rhamnose, sucrose, lactose, trehalose, maltose, raffinose, panose, malto Triose residues, melezitose residues, gentianose residues, stachyose residues and the like can be mentioned.
Sphingophospholipids are those in which a phosphate group is bound to the ceramide described above, and those in which the phosphate group is released and choline is bound. In (Chemical Formula 1), R ¹ and R ² are the same as ceramide. , R ³ includes a phosphate group, a phosphocholine residue, a phosphoserine residue, a phosphoethanolamine residue, a phosphoinositol residue, and the like.

The sphingolipid used in the composition of the present invention is derived from raw materials such as animals, plants, microorganisms, etc., and processed products obtained by crushing or crushing them may be used directly, or they may be separated. -You may use what was obtained by methods, such as extraction etc. or artificial synthesis.
Examples of raw materials containing sphingolipid include animals such as cattle, pigs, horses, cottonseed, sugar beet, rice cake, rapeseed, sugar cane, sesame, peanuts, soybeans, corn, rice, wheat, pineapple, eggplant, tangerine, apples Plants, mushrooms such as scallops, foods such as milk, yeasts and the like.
The method for extracting and separating the sphingolipid from the raw material and the synthesis method are not particularly limited, and can be appropriately selected according to the purpose. Examples of the extraction method include a method in which an extraction solvent usually used by those skilled in the art, such as ethanol, water, and water-containing ethanol, is added and heated as necessary for extraction.
Further, the crushing and pulverizing method for obtaining the sphingolipid from the raw material is not particularly limited, and may be either wet or dry, and the pulverizing conditions and the processing apparatus are not particularly limited, and a commercially available apparatus or the like may be used as appropriate. it can. Examples of the apparatus to be used include a high-pressure homogenizer, an ultrasonic pulverizer, an airflow pulverizer, a high-speed rotational impact pulverizer, a ball mill, or a bead mill.
These treatments may be repeated a plurality of times as necessary so that the physical properties such as the particle diameter of the processed product are within a preferable range, or a plurality of treatments may be combined.
In the present invention, among sphingolipids, glycosphingolipids are preferred, and among these glycosphingolipids, glucosylceramide (a glucose residue bonded to a hydroxyl group at the ceramide terminal), particularly glucosylceramide derived from rice, is used. It is more preferable.
There is no restriction | limiting in particular as content of the sphingolipid mix | blended with the composition of this invention, According to various conditions, such as an objective, a shape, and a use object, the content can be suitably set in a wide range. For example, it is selected in the range of 0.00001 to 90% by mass, preferably 0.0001 to 10% by mass, more preferably 0.0001 to 1% by mass.

The saponin used in the composition of the present invention is a 7-O-glucoside of isovitexin (saponaretin), and is known as a component that contributes to the characteristic green color of flowers, which is contained in mugwort, jade vine, and the like.
In the composition of the present invention, the saponin may be obtained by directly using a processed product obtained by crushing or crushing a saponin-containing plant or the like, or by a method such as separation / extraction or artificial synthesis. You may use what you get.
Treatments such as crushing and pulverization, extraction methods, synthesis methods, and the like are not particularly limited, and can be appropriately selected according to the purpose as in the case of sphingolipids.
The content of saponin in the composition of the present invention is not particularly limited, and the content can be appropriately set over a wide range according to various conditions such as the purpose, shape, and intended use. For example, it is selected in the range of 0.00001 to 90% by mass, preferably 0.0001 to 10% by mass, more preferably 0.0001 to 1% by mass with respect to the composition of the present invention.
Make

The composition of the present invention may contain other components in addition to the sphingolipid and saponaline.
Examples of other components include: proteins such as gelatin and collagen peptides; water-soluble dietary fibers such as alginic acid, indigestible dextrin, guar gum, guar gum, glucomannan, polydextrose, and fucoidan; cellulose, hemicellulose, pectin, and lignan Insoluble dietary fiber such as calcium, magnesium and iron; mucopolysaccharides such as N-acetylglucosamine, hyaluronic acid and chondroitin sulfate; milk, fermented milk, skim milk powder, etc. Dairy products; soy milk products such as soy milk, soy milk powder; plants or plant processed products such as lemon, apple, tomorrow, kale, sweet potato, sweet potato foliage, potato, carrot, pumpkin, bitter gourd, tomato, green peas, morohaya; spirulina Algae etc. ; Can be formulated lactic acid, Bacillus natto, butyric acid bacteria, Aspergillus, microorganisms such as yeast. Furthermore, sugars such as dextrin, glucose, lactose, sucrose, maltose, fructose, erythritol, trehalose, maltitol, xylitol, starch, beet oligosaccharide, soybean oligosaccharide, xylooligosaccharide Oligosaccharides such as fructooligosaccharides and isomaltoligosaccharides, sweeteners such as stevia, acesulfame potassium, sucralose, aspartame, thaumatin, and reduced maltose; acidulants such as citric acid, lactic acid, gluconic acid, and apples; colorants such as titanium oxide; Thickeners such as gum arabic and xanthan gum; brighteners such as shellac; excipients such as talc, silicon dioxide, cellulose, calcium stearate; vitamins such as vitamin A, vitamin C, vitamin E, royal jelly, protein, chitosan, Prosperity such as lecithin Adjuvants, other, various binders, lubricants, stabilizers, diluents, fillers, emulsifiers, colorants, flavors, food additives, may be mentioned seasonings.
The content of these other components can be appropriately selected according to the form of the composition of the present invention.

The composition of the present invention can be taken as appropriate according to the purpose such as oral or dermal, and there are no particular restrictions on the intake method, intake, number of intakes, intake time, and intake target.
Moreover, it can select suitably according to various factors and objectives, such as age of an ingestion individual, a body weight, a constitution.

The shape when ingesting the composition of the present invention is not particularly limited, and in the case of an oral composition, specific shapes include, for example, powder and granule powder, tablet (chewable), spherical, and capsule shapes , Caplet-like, bowl-like, rod-like, plate-like, block-like, wafer-like, biscuit-like, gummy-like solids; gel-like, cream-like, jelly-like semi-solids; syrup-like, liquid-like fluids And the like. The capsule-like oral composition includes soft capsules and hard capsules, and the liquid oral composition includes carbonated drinks, coffee drinks, tea-based drinks, mineral water, flavored water, sports / functional drinks, fruit drinks, milk This includes beverages, milk drinks, soy milk drinks, vegetable drinks, and nutritional drinks (mini-drinks).
By making the oral composition into a powdered beverage, it is easy to process sphingolipids and saponarins, and it is excellent in stability as a composition, and in contrast to capsules and tablets, etc., ingest many compositions at once. Is preferable. The composition of the present invention may be a composition for oral cavity such as dentifrice and mouthwash.
In the case of a transdermally absorbable composition, sphingolipid and saponin may be used as they are, such as processed products and extracts, as in the case of oral compositions, and fatty acids such as stearic acid; cetanol, octyl Prepare a composition by a commonly used method by mixing with other components such as alcohols such as dodecanol, 1,3 butylene glycol, glycerin; colorants such as iron oxide and titanium oxide; functional materials such as squalane. May be. Specific forms include, for example, basic cosmetics such as lotions, cosmetic liquids, emulsions, creams, ointments, lotions, oils, packs, etc .; skin cleansing agents such as soaps, cleansing creams, cleansing lotions, cleansing milks, face wash Shampoo, conditioner, hair wash cosmetics; hair cream, hair spray, hair tonic, hair gel, hair lotion, hair oil, hair essence, hair water, hair wax, hair foam, etc. Hair dyes such as one-part hair dye, two-part hair dye, hair color, permanent hair such as permanent wave agent and hair straightener, and hair cosmetics such as wave retainer; foundation, white powder, white hair, lipstick Makeup makeup such as blusher, eye shadow, eyeliner, mascara, eyebrows, eyelashes, etc. Cosmetics for finishing such as nail care; perfumes, bathing agents, anti-inflammatory agents, anti-odor agents, hair cosmetics for preventing dandruff or itching, hair loss inhibitors, hair removal agents, shaving agents, sunburn Examples thereof include a stop agent, an acne preventive or ameliorating agent, oily skin cosmetics, hygiene products, sanitary cotton, and wet tissue.

The blending ratio (weight ratio) of the sphingolipid and saponaline in the composition of the present invention is not particularly limited and can be appropriately set according to the conditions such as the purpose and the object of use, sphingolipid: saponaline = 1: 0.01 to 1000. , Preferably 1: 0.1-500, more preferably 1: 0.1-200.

  When preparing the composition of the present invention, sphingolipids and saponarins may be extracted, separated, synthesized, or processed raw materials containing them as they are, but they may be used as an additive such as dextrin and silicon dioxide. You may mix and shape with a shape agent, a bulking agent, a binder, a thickener, an emulsifier, etc., and you may use it. Further, it may be used by dissolving or dispersing in a solvent such as water (purified water or the like), edible oil (corn oil or the like).

Hereinafter, the present invention will be specifically described by way of examples. The present invention is not limited to these examples.

<CLDN1 expression promoting action>
Example 1
First, human epidermal keratinocytes (9 passages, manufactured by PromoCell) previously cultured using a keratinocyte growth medium 2 kit (PromoCell) are 5 × 10 ^ 4 cells / well. Inoculated in a 24-well plate and pre-cultured for 24 hours in a 37 ° C. 5% CO ₂ incubator.
Next, as a sample, glucosylceramide, which is one type of glycosphingolipid, and saponaline are prepared, and a keratinocyte growth medium (PromoCell) containing glucosylceramide at a concentration of 15 μg / mL and saponaline at a concentration of 1.5 μg / mL. Prepared.
Next, the medium in which the human epidermal keratinocytes were cultured was removed, replaced with the medium containing the sample, and further cultured in a 5% CO ₂ incubator at 37 ° C. for 40 hours.
After culturing, the culture supernatant is removed, RNA is collected from the cells using an RNA extraction kit (RNeasy mini kit: QIAGEN), and the RNA is recovered using a reverse transcription reaction kit (Quantitative Reverse Transcription Kit: QIAGEN). cDNA was synthesized.
Using the obtained cDNA, the expression level of mRNA encoding CLDN1, which is one of tight junction constituent proteins, was measured. As an internal standard, the amount of GAPDH mRNA expression was also measured. As a control, the same operation was performed using a medium containing no sample.
The expression level [%] of mRNA encoding CLDN1 was calculated from the following formula: expression level [%] = (mRNA expression level in medium containing sample) / (mRNA expression level in medium not including sample) × 100.

The glucosylceramide used is glucosylceramide extracted from rice, and includes glucosylceramide having the structures (a) to (f) shown in (Chemical Formula 2). In [Chemical Formula 2], in [A: B] in the structure of the fatty acid, A represents the number of carbon atoms of the fatty acid, and B represents the number of double bonds in the fatty acid. In the description of [C: D] in the structure of the sphingoid base, d represents that the 4-position carbon atom does not have a hydroxyl group, t represents that the 4-position carbon atom has a hydroxyl group, and C represents a sphingoid base. The carbon number of D, D represents the number of double bonds in the sphingoid base. In the superscript symbol attached to the number D of double bonds, the number represents the position of the double bond, E and Z are the types of double bonds (E is a trans double bond, Z is a cis type two bond). Represents a double bond). For example, in the case of (a) glucosylceramide, a saturated fatty acid having 20 carbon atoms and a sphingoid base are bonded to each other, and the sphingoid base has 18 carbon atoms and the trans double bonds are in the 4th and 8th positions. It represents that there is no hydroxyl group at the 4-position carbon atom.

(Example 2)
The procedure was the same as Example 1 except that the concentration of saponin in the sample was 15 μg / mL.

Example 3
The same procedure as in Example 1 was performed except that the concentration of saponaline in the sample was changed to 150 μg / mL.

Example 4
The procedure was the same as Example 1 except that the concentration of saponin in the sample was 1500 μg / mL.

(Comparative Example 1)
Example 1 was repeated except that only glucosylceramide was used as a sample and the concentration was 15 μg / mL.

(Comparative Example 2)
The procedure was the same as Example 1 except that only saponin was used as a sample and the concentration was 15 μg / mL.
The results are shown in FIG. The expression level represents the expression level relative to the control.

From FIG. 1 and Table 1, in Example 1 containing glucosylceramide and saponin in a weight ratio of 1: 0.1, the expression level of mRNA encoding CLDN1 is 126%, and the expression promoting effect of CLDN1 is obtained. I understood. In addition, Example 2 in which the weight ratio of glucosylceramide and saponin was 1: 1 was 133%, and Example 3 in which the weight ratio of glucosylceramide and saponaline was 1:10 was 155%, and the weight of glucosylceramide and saponin. Example 4 having a ratio of 1: 100 has an expression level of 140%, and it was confirmed that the expression of CLDN1 was promoted by adjusting the blending amount of saponarine to glucosylceramide to a predetermined ratio.
On the other hand, in Comparative Example 1 using only glucosylceramide as a sample, the expression level of mRNA encoding CLDN1 was 98%, and in Comparative Example 2 using only saponin as a sample, the expression level of mRNA encoding CLDN1 was 93%. , CLDN1 expression promoting effect was not obtained.

From the above, it was confirmed that the sphingolipids glucosylceramide and saponaline alone do not promote the expression of CLDN1, but the combination of glucosylceramide and saponaline synergistically promotes the expression of CLDN1.
In addition, as can be seen from Example 1, the amount of saponarine blended with glucosylceramide, even in a small amount of 1.5 μg / mL (concentration of 1/10 compared to Comparative Example 2), It was confirmed that an expression promoting effect was obtained.
Thereby, the composition of the present invention containing sphingolipid and saponaline has an expression promoting action of CLDN1, can promote the formation of tight junctions, and can enhance and improve the skin barrier function. The moisturizing effect of the skin can be enhanced and the skin can be prevented from drying, and itching can be suppressed and rough skin can be improved.

Although the compounding example of the composition of this invention is described below, this invention is not limited to the following compounding examples.

(Formulation Example 1: Granules)
Each component is mixed in a flow coater NFL-200 fluidized bed granulator (made by Freund Sangyo Co., Ltd.) at the blending ratio shown in Table 2, mixed for several minutes with an air stream, and granulated by spraying water on it. Went. The obtained granulated product was sieved with a 30-mesh sieve to obtain granules.

(Formulation Example 2: Granules)
Granules were prepared using the same method as in Formulation Example 1 at the blending ratio in Table 3.

(Formulation Example 3: Tablet)
Each component was mix | blended with the mixture ratio of Table 4, and it tableted according to the usual method, and manufactured the tablet.

(Formulation Example 4: Tablet)
Each component was mix | blended with the mixture ratio of Table 5, and it tableted according to the usual method, and manufactured the tablet.

(Formulation example 5: soft capsule)
The internal solution which mix | blended each component with the mixture ratio of Table 6 was prepared, and it encapsulated softly according to the usual method.

(Formulation example 6: hard capsule)
A composition was prepared at a blending ratio shown in Table 7, and was hard-encapsulated according to a conventional method.

(Formulation example 7: salmon)
Each component was blended at the blending ratios shown in Table 8 to produce straw.

(Formulation example 8: liquid beverage)
Each component was mix | blended with the mixture ratio of Table 9, and the liquid drink was manufactured.

(Formulation example 9: gummi)
Each component was blended at the blending ratio shown in Table 10, and put in a mold according to a conventional method and molded to produce a gummy.

(Formulation example 10: powdered beverage)
Granules were prepared using the same method as in Formulation Example 1 at the blending ratio shown in Table 11, and the powdered beverage was taken by being dispersed and dissolved in a liquid such as water or hot water.

(Formulation example 11: jelly)
Each component was blended at a blending ratio shown in Table 12, and placed in a mold and molded according to a conventional method to produce a jelly.

(Formulation example 12: gum)
Each component was blended at a blending ratio shown in Table 13, and put into a mold according to a conventional method to form a gum.

  ADVANTAGE OF THE INVENTION According to this invention, while the expression of CLDN1 is accelerated | stimulated, formation of a tight junction can be promoted, the composition which can reinforce and improve the barrier function of skin can be provided, and the moisturizing effect of skin It is possible to provide a composition that can prevent skin dryness, suppress itching of the skin, and improve rough skin.

Claims (10)

A cosmetic composition comprising a rice-derived sphingolipid and saponaline. A skin dryness prevention / improving composition comprising a rice-derived sphingolipid and saponin. A composition for improving rough skin, comprising a sphingolipid derived from rice and saponin. A skin moisture transpiration inhibiting composition comprising a rice-derived sphingolipid and saponaline. A skin moisturizing composition comprising rice-derived sphingolipid and saponin. A composition for improving skin barrier function, comprising a sphingolipid derived from rice and saponaline. A skin itch suppression composition comprising a rice-derived sphingolipid and saponaline. A composition for enhancing tight junction function, comprising a sphingolipid derived from rice and saponaline. A claudin-1 expression promoting composition comprising rice-derived sphingolipid and saponin. The composition according to any one of claims 1 to 9, wherein the rice-derived sphingolipid is glucosylceramide.