JP5203084B2 - Dispersed hesperetin - Google Patents

Description

  The present invention relates to hesperetin. More specifically, the present invention relates to a hesperetin dispersion, a powder containing hesperetin particles, and a production method thereof.

  Hesperidin is known to have various physiological activities. Hesperidin is, for example, an action that lowers blood pressure, an antiallergic action, an action that reduces LDL-cholesterol and improves blood cholesterol level, an anticancer action, an action that reduces the permeability and vulnerability of capillary walls, and suppresses colitis It has an action, an arthritis inhibitory action, a platelet and cell aggregation inhibitory action and the like.

  In the natural state, hesperidin exists in the form of a glycoside in which a sugar is bound to hesperetin. Hesperetin is an aglycon of hesperidin. Hesperidin is considered to be taken into the body from the large intestine after being ingested by animals and then hydrolyzed into sugar and aglycone by enzymes produced by bacteria present in the intestinal tract.

  Thus, hesperidin and hesperetin have very excellent physiological effects. Moreover, since hesperidin is present in a large amount in citrus fruits, the raw material can be obtained easily and inexpensively. Nevertheless, the use of hesperidin and hesperetin is very limited. This is because hesperidin and hesperetin are hardly soluble in water. Hesperidin and hesperetin are less soluble in water than hesperetin. In general flavonoids, aglycone and its glycoside have a lower solubility in water and a lower absorption amount in the body. However, in the case of hesperidin and hesperetin, non-patent document 1 shows that hesperetin, which is an aglycon, is more easily absorbed than hesperidin, which is a glycoside. Therefore, it is preferable to use hesperetin more actively than hesperidin.

  However, since hesperetin has low solubility in water, it immediately precipitates when hesperetin is added to a beverage or the like, and most of hesperetin remains at the bottom of the beverage container. Therefore, the added hesperetin cannot be taken into the body effectively. Therefore, it is difficult to become a product that can appeal to consumers. Therefore, it is desirable to stably disperse hesperetin in the beverage.

  Conventionally, the dispersion | distribution to water is examined about various water-insoluble matter. For example, Patent Document 1 discloses a mineral-containing composition comprising an enzymatically decomposed lecithin and a water-insoluble mineral. Patent Document 2 discloses an antioxidant composition comprising ferric pyrophosphate coated with an emulsifier. Patent Document 3 discloses a polyglycerin fatty acid ester that makes it possible to produce a solubilizate or a stable emulsion that was not possible with conventional surfactants.

  However, what is described as an object to be dispersed in Patent Document 1 and Patent Document 2 are inorganic substances such as a water-insoluble mineral and ferric pyrophosphate, respectively, which are completely different in nature from hesperetin, which is an organic substance.

  Patent Document 3 describes hydrophobic substances such as fat-soluble vitamins such as vitamin E, oil-soluble pigments such as β-carotene, and oil-soluble physiologically active substances such as highly unsaturated fatty acids. . These are all substances that are liquid at room temperature, and are completely different from hesperetin that is solid at room temperature.

Thus, conventionally, hesperetin could not be stably dispersed in water.
International Publication No. 98/14072 Pamphlet JP 2005-239893 A JP 2006-111539 A Boot AN et al., Metabolic fate of hesperidin, erodidictol, homoerodytyol and diosmin, J. et al. Biol. Chem. 230: 661-668 (1958)

  The present invention is intended to solve the above-described problems, and an object of the present invention is to provide a stable hesperetin dispersion, a powder containing hesperetin particles, and a production method thereof.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have obtained a dispersion in which hesperetin particles are dispersed significantly more stably than in the past by using a specific surfactant. Based on this, the present invention has been completed.

In order to achieve the above object, the present invention provides, for example, the following means:
(Item 1)
A hesperetin dispersion liquid comprising hesperetin particles, a surfactant and a solvent, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzymatically decomposed lecithin.

(Item 2)
Item 2. The dispersion according to Item 1, wherein the surfactant comprises polyglycerin fatty acid ester and enzyme-degraded lecithin.

(Item 3)
Item 3. The dispersion according to Item 1 or 2, wherein the surfactant comprises polyglycerin fatty acid ester, glycerin fatty acid organic acid ester, and enzymatically decomposed lecithin.

(Item 4)
The polyglycerol fatty acid ester is formed by esterification of polyglycerol and a fatty acid, the hydroxyl value of the polyglycerol is 1200 or less, and the primary among all the hydroxyl groups of the polyglycerol Item 4. The dispersion according to any one of Items 1 to 3, wherein the hydroxyl group is 50% or more.

(Item 5)
Item 5. The dispersion according to Item 4, wherein the formed polyglycerol fatty acid ester is decaglycerol monooleate.

(Item 6)
The surfactant includes decaglycerin monooleate formed by esterification of decaglycerin and oleic acid, glyceryl monoesterate glycerin, and enzymatically decomposed lecithin, and the hydroxyl value of the decaglycerin is 1200. Item 6. The dispersion according to any one of Items 1 to 5, wherein the primary hydroxyl group is 50% or more of all the hydroxyl groups of the decaglycerin.

(Item 7)
Furthermore, the dispersion liquid of any one of the items 1-6 containing a polysaccharide.

(Item 8)
Item 8. The dispersion according to Item 7, wherein the polysaccharide is selected from the group consisting of alginic acid and alginic acid ester.

(Item 9)
Item 8. The dispersion according to Item 7, wherein the polysaccharide is an alginate.

(Item 10)
Item 10. The dispersion according to any one of Items 1 to 9, wherein the average particle size of the hesperetin particles is 0.1 µm to 10 µm.

(Item 11)
Item 11. The dispersion according to any one of Items 1 to 10, wherein the content of hesperetin particles in the hesperetin dispersion is 1 wt% to 50 wt%.

(Item 12)
Item 12. The dispersion according to any one of Items 1 to 11, wherein precipitation is not substantially observed after standing for 24 hours.

(Item 13)
A powder comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzyme-degraded lecithin.

(Item 14)
Item 14. The powder according to Item 13, wherein the surfactant comprises polyglycerin fatty acid ester and enzyme-degraded lecithin.

(Item 15)
Item 15. The powder according to Item 13 or 14, wherein the surfactant comprises polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzyme-degraded lecithin.

(Item 16)
The polyglycerol fatty acid ester is formed by esterification of polyglycerol and a fatty acid, the hydroxyl value of the polyglycerol is 1200 or less, and the primary among all the hydroxyl groups of the polyglycerol Item 6. The powder according to any one of Items 13 to 5, wherein the hydroxyl group is 50% or more.

(Item 17)
Item 17. The powder according to Item 16, wherein the formed polyglycerol fatty acid ester is decaglycerol monooleate.

(Item 18)
The surfactant includes decaglycerin monooleate formed by esterification of decaglycerin and oleic acid, glyceryl monoesterate glycerin, and enzymatically decomposed lecithin, and the hydroxyl value of the decaglycerin is 1200. Item 18. The powder according to any one of Items 13 to 17, wherein the primary hydroxyl group is 50% or more of all the hydroxyl groups of the decaglycerin.

(Item 19)
Furthermore, the powder of any one of the items 13-18 containing a polysaccharide.

(Item 20)
Item 20. The powder according to Item 19, wherein the polysaccharide is selected from the group consisting of alginic acid and alginic acid ester.

(Item 21)
Item 20. The powder according to Item 19, wherein the polysaccharide is an alginate.

(Item 22)
Item 22. The powder according to any one of Items 13 to 21, wherein the average particle size of the hesperetin particles is 0.1 μm to 10 μm.

(Item 23)
Item 23. The powder according to any one of Items 13 to 22, wherein the content of the hesperetin particles in the powder is 30% to 95% by weight.

(Item 24)
A food or drink comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzyme-degraded lecithin.

(Item 25)
A quasi-drug comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzyme-degraded lecithin.

(Item 26)
A pharmaceutical comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzyme-degraded lecithin.

(Item 27)
A skin external preparation containing hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzyme-degraded lecithin.

(Item 28)
A bathing agent comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzymatically decomposed lecithin.

(Item 29)
A feed comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzyme-degraded lecithin.

(Item 30)
A pet food comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzyme-degraded lecithin.

(Item 31)
A fiber comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzyme-degraded lecithin.

(Item 32)
A garment comprising hesperetin particles and a surfactant, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzymatically degraded lecithin.

(Item 33)
A method for producing a hesperetin dispersion according to item 1, wherein the method comprises:
A method comprising mixing a hesperetin bulk powder, a surfactant and a solvent to obtain a mixture; and grinding the mixture with a wet grinder to obtain a hesperetin dispersion.

(Item 34)
The method for producing a powder according to item 13, wherein the method comprises:
Mixing hesperetin powder, a surfactant and a solvent to obtain a mixture;
A method comprising: subjecting the mixture to a wet grinder to pulverize the hesperetin bulk powder in the mixture to obtain a hesperetin dispersion; and drying the hesperetin dispersion to obtain a hesperetin powder.

(Item 35)
35. A method according to item 34, wherein the drying is performed by spray drying.

  The hesperetin dispersion of the present invention has an effect that precipitation does not substantially occur even when stored for a long period of time. There is also an effect that the problem of thickening does not occur in the production process of the hesperetin dispersion of the present invention.

  Hereinafter, the present invention will be described in detail.

(1. Material of hesperetin dispersion)
The hesperetin dispersion of the present invention contains hesperetin particles, a surfactant and a solvent. The material of the hesperetin dispersion of the present invention will be described in more detail below.

(1.1 Hesperetin particles)
Hesperetin is also called 3 ', 5,7-trihydroxy-4'-methoxyflavanone. Hesperetin has the following structure:

Hesperetin is an aglycon of hesperidin. Hesperetin can be obtained by degrading hesperidin with hesperidinase or naringinase. Hesperidin is a kind of flavonoid, and is contained in the fruits of citrus fruits (for example, Unshu orange, Summer orange, Iyo orange, Navel orange, Valencia orange), and especially in Unshu orange. Hesperidin is contained in large amounts in tangerine fruits in the immature period. Hesperidin is the most abundant in the white mesocarp, which is between the yellow rind and the flesh, among the parts of Wenzhou mandarin fruit. Hesperidin can be extracted from citrus peel, fruit juice or seed. For example, when extracting hesperidin from a squeezed strawberry of Unshu mandarin fruit, after adjusting the pH to 11.5 to 12.5 by adding calcium hydroxide and sodium hydroxide solution to the squeezed strawberry of Unshu mandarin fruit The mixture is stirred and squeezed, and the resulting liquid is centrifuged. Acid is added to the supernatant obtained by centrifugation to adjust the pH to 5 to 5.5, and then the mixture is heated. The solution is centrifuged to precipitate hesperidin, and then the precipitated hesperidin is recovered. A method is shown (see JP-A-8-188593). Subsequently, hesperetin can be obtained by preparing an aqueous hesperidin solution and removing the sugar moiety (eg, by the action of naringinase or hydrolysis under acidic conditions). Details of methods for obtaining hesperidin from citrus fruits are described, for example, in King FE and Robertson A. et al. , Natural glucosides, Part3. J. et al. Chem. soc. (II): 1704-1709 (1931). Alternatively, commercially available hesperidin may be used as a raw material. Hesperidin is sold, for example, by Hamari Sangyo Co., Ltd. Hesperetin is an aglycon of hesperidin. Details of the method for obtaining hesperetin from hesperidin by acid degradation are described in, for example, Asahina Y. et al. Flavanone glucosides (V): Reduction of flavone and flavonol derivatives, J. et al. Pharm. Soc-Japan 50: 217-223 (1931). Hesperetin can also be obtained by enzymatic degradation of hesperidin with rhamnosidase and glucosidase.

  Hesperetin is a colorless needle or plate crystal, and its melting point is 227-228 ° C. In the present specification, “hesperetin bulk powder” refers to solid hesperetin that has not been subjected to particle formation treatment. Needle-like or plate-like hesperetin is hesperetin bulk powder.

  In the present specification, “hesperetin particles” refers to solid hesperetin divided into particles. The average particle size of the hesperetin particles is preferably about 10 μm or less, more preferably about 5 μm or less, further preferably about 3 μm or less, particularly preferably about 2 μm or less, and most preferably about 1 μm or less. is there. There is no particular lower limit to the average particle size of the hesperetin particles, but for example, about 0.01 μm or more, about 0.05 μm or more, about 0.1 μm or more, about 0.2 μm or more, about 0.3 μm or more, about 0.4 μm or more , About 0.5 μm or more. In order to facilitate dispersion, the average particle size of the hesperetin particles should be as small as possible.

  Of the entire hesperetin particles, the particle size of the particles is preferably about 80% by volume or more, more preferably about 90% by volume or more, further preferably about 95% by volume or more, and most preferably about 99% by volume or less. It is preferably about 0.8 μm or less, and most preferably about 0.5 μm or less.

  The hesperetin particles having such an average particle size can be obtained by pulverizing hesperetin bulk powder by a physical pulverization method using a wet pulverizer such as dyno mill, ready mill or coball mill, or a dry pulverizer such as a jet mill. The average particle size of the hesperetin particles can be measured by, for example, a wet particle size distribution meter manufactured by Beckman Coulter.

(1.2 Surfactant)
In the present specification, the “surfactant” refers to a substance having a hydrophilic group and a lipophilic group in a molecule and exhibiting surface activity at the interface of a solution or at the interface of a liquid and a solid. . The surfactant used in the present invention is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically decomposed lecithin. These surfactants may be used alone or in combination of two or more. It is preferable to use a combination of two or more. In addition to a surfactant selected from the group consisting of polyglycerol fatty acid esters, glycerol fatty acid organic acid esters and enzymatically decomposed lecithins, other general surfactants may be used in combination. Examples of such other general surfactants include nonionic interfaces such as glycerin fatty acid esters, propylene glycol fatty acid esters, organic acid monoglycerides, monoglyceride derivatives, sucrose fatty acid esters, sorbitan fatty acid esters, and polyoxyethylene derivatives. Surfactant: Amphoteric surfactant; Anionic surfactant; Cationic surfactant; Surfactant derived from natural products such as lecithin, enzymatically decomposed lecithin, saponin, quilla extract and the like. These general surfactants may be used alone or in combination of two or more.

  Preferably, the surfactant used in the present invention includes polyglycerin fatty acid ester and enzymatically degraded lecithin. The combined use of polyglycerin fatty acid ester and enzyme-degraded lecithin increases the stability of the hesperetin dispersion.

  More preferably, the surfactant used in the present invention includes polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzyme-degraded lecithin. The combined use of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzyme-degraded lecithin greatly increases the stability of the hesperetin dispersion.

  The blending amount of these surfactants in the dispersion is not particularly limited. If the blending amount is too small, the dispersion state in water may become unstable, and if the blending amount is too large, the viscosity of the dispersion becomes high and handling of the dispersion may be inconvenient. From such a viewpoint, the blending amount of the surfactant is preferably about 0.01% by weight or more, more preferably about 0.05% by weight or more, and further preferably about 0.1% by weight. More preferably, it is about 0.5% by weight or more, and most preferably about 1% by weight or more. When the dispersion is relatively dilute, such as a beverage that is used as it is, the amount of the surfactant is preferably about 0.01% by weight or more, more preferably about 0.02% by weight. % Or more, more preferably about 0.03% by weight or more, particularly preferably about 0.04% by weight or more, and most preferably about 0.05% by weight or more. If the dispersion is relatively thick, such as a stock solution for making a dilute dispersion, the surfactant loading may be, for example, about 0.1, depending on the intended concentration. % By weight or more, about 0.5% by weight or more, about 1.0% by weight or more, about 5% by weight or more, about 10% by weight or more.

  The blending amount of the surfactant is preferably about 10% by weight or less, more preferably about 5% by weight or less, and further preferably about 3% by weight or less. When the dispersion is relatively dilute, such as a beverage that is used as it is, the amount of the surfactant is preferably about 1% by weight or less, more preferably about 0.5% by weight or less. More preferably about 0.4% by weight or less, still more preferably about 0.3% by weight or less, particularly preferably about 0.2% by weight or less, most preferably about 0.1% by weight or less. % By weight or less. If the dispersion is relatively thick, such as a stock solution for making a dilute dispersion, the surfactant loading may be, for example, about 10% by weight, depending on the intended concentration. Hereinafter, it may be about 5 wt% or less, about 3 wt% or less, about 2 wt% or less, about 1 wt% or less.

(1.2.1 Polyglycerin fatty acid ester)
The “polyglycerin fatty acid ester” used in the present invention refers to an esterification of a glycerin condensate and a fatty acid. Polyglycerin refers to a compound having a polymerization degree of 2 or more obtained by dehydration condensation of glycerin. The polyglycerin fatty acid ester may be a monoester, a diester, a triester, or a further esterified ester. Preferably, the polyglycerol fatty acid ester is a polyglycerol fatty acid monoester. Polyglycerol fatty acid esters are generally marketed as mixtures of polyglycerol fatty acid esters of various degrees of polymerization. Such commercially available mixtures are available in various grades depending on the degree of polymerization, the type of fatty acid ester, and the like. As the polyglycerin fatty acid ester, for example, generally, a polyglycerin fatty acid ester mixture whose main component is a glycerin condensation degree of 2, 3, 4, 5, 6 or 10 is commercially available. Can be used. Among them, those having a highly hydrophilic glycerin condensation degree of 5 or more can be suitably used. As polyglycerol fatty acid ester, what consists of 1 type of polyglycerol fatty acid ester may be used, and the mixture of multiple types of polyglycerol fatty acid ester may be used. It is preferable to use a specific type of polyglycerol fatty acid ester having as high a purity as possible.

More preferably, the polyglycerol fatty acid ester is formed by esterification of polyglycerol and a fatty acid, and the hydroxyl value of the polyglycerol is 1200 or less, and the primary hydroxyl group among all hydroxyl groups. Is 50% or more. The hydroxyl value is one of the characteristics of oils and waxes. “Hydroxyl value” means the number of mg of potassium hydroxide required to neutralize acetic acid bound to acetylated product obtained from 1 g of sample oil. The sample is heated with an excess of an acetylating agent (for example, acetic anhydride), acetylated, and the saponification value of the resulting acetylated product is measured and then calculated according to the following formula:
Hydroxyl value = {A / (1-0.00075A)}-B
(However, A represents a saponification value after acetylation, and B represents a saponification value before acetylation).

  The polyglycerin used for forming the polyglycerin fatty acid ester is preferably a polyglycerin having a primary hydroxyl group of 50% or more of all the hydroxyl groups in the polyglycerin. From the viewpoint of solubilization performance of the resulting polyglycerin fatty acid ester and high emulsification stability, a polyglycerin having a primary hydroxyl group ratio of about 55% or more is more preferable, and a polyhydroxylamine having a primary hydroxyl group ratio of about 60% or more is more preferable. Most preferred is glycerin. Furthermore, the hydroxyl value of the polyglycerol used for forming the polyglycerol fatty acid ester is more preferably about 1100 or less, and preferably about 1000 or less, from the viewpoint of the hydrophilic / hydrophobic balance (HLB) of the polyglycerol fatty acid ester. More preferably, it is particularly preferably about 950 or less, most preferably about 900 or less. From the viewpoint of workability and ease of esterification with a fatty acid, the hydroxyl value of the polyglycerol used for forming the polyglycerol fatty acid ester is preferably about 770 or more, preferably about 800 or more, Particularly preferred is about 850 or more.

Hydrophilic Lipophile Balance, generally calculated by 20 × M _H / M, where M _H = molecular weight of the hydrophilic group moiety and M = molecular weight of the entire molecule. The HLB value is 0 when the amount of the hydrophilic group in the molecule is 0%, and 20 when the amount is 100%. The HLB value represents the size and strength of the hydrophilic and hydrophobic groups that form the emulsifier molecule in the emulsifier, the emulsifier having high hydrophobicity has a small HLB value, and the emulsifier having high hydrophilicity has a large HLB value.

The proportion of primary hydroxyl groups among all hydroxyl groups is measured using a method of measuring a nuclear magnetic resonance spectrum (NMR) for carbon atoms. The hydroxyl value can be measured by a method known in the art. The nuclear magnetic resonance spectrum (NMR) for carbon atoms can be measured as follows. Polyglycerin 500 mg is dissolved in 2.8 ml of heavy water, and after filtration, ¹³ C-NMR (125 MHz) spectrum is obtained by gated decoupling. The peak intensity is proportional to the carbon number by the gate decoupled measurement method. The ¹³ C chemical shifts indicating the presence of primary hydroxyl groups and secondary hydroxyl groups are about 63 ppm for methylene carbon (CH ₂ OH) and about 71 ppm for methine carbon (CHOH), respectively. The abundance ratio of the primary hydroxyl group and the secondary hydroxyl group is calculated. However, the methine carbon (CHOH) indicating the secondary hydroxyl group overlaps with the methylene carbon peak further adjacent to the methine carbon bonded to the methylene carbon indicating the primary hydroxyl group, and the integral value of itself cannot be obtained. The integrated value is calculated from the signal intensity around 74 ppm of methylene carbon (CH ₂ ) adjacent to (CHOH). A polyglycerin fatty acid ester formed by esterification of a polyglycerin having a hydroxyl value of 1200 or less and a primary hydroxyl group of 50% or more of all the hydroxyl groups of polyglycerol and a fatty acid is, for example, It can be produced according to the method described in Japanese Unexamined Patent Publication No. 2006-111539. The polyglycerol fatty acid ester formed is preferably decaglycerol monooleate.

  Most preferably, the surfactant comprises decaglycerin monooleate formed by esterification of decaglycerin and oleic acid, glyceryl monostearate glycerin, and enzymatically decomposed lecithin, and the hydroxyl group of the decaglycerin The value is 1200 or less, and the primary hydroxyl group of all the hydroxyl groups of decaglycerin is 50% or more.

  The fatty acid that is another component that reacts with polyglycerol to form a polyglycerol fatty acid ester may be an aliphatic monocarboxylic acid or an aliphatic dicarboxylic acid. Preferably, it is an aliphatic monocarboxylic acid.

  Fatty acids can be obtained by hydrolyzing oils and fats extracted from natural animals and plants and purifying them with or without separation. Alternatively, the fatty acid may be a fatty acid obtained by chemically synthesizing petroleum or the like as a raw material. Fatty acids may also be reduced by hydrogenation of these fatty acids, condensed fatty acids obtained by condensation polymerization of fatty acids containing hydroxyl groups, or polymerized fatty acids obtained by heat polymerization of fatty acids having unsaturated bonds. Good. The selection of these fatty acids may be appropriately determined in consideration of the desired effect.

  The fatty acid is a fatty acid having 3 or more carbon atoms. The number of carbon atoms of the fatty acid is preferably 6 or more, more preferably 8 or more, still more preferably 10 or more, particularly preferably 12 or more, particularly preferably 14 or more, more preferably 15 It is above, More preferably, it is 17 or more. The number of carbon atoms of the fatty acid is preferably 22 or less. The fatty acid may be a saturated fatty acid or an unsaturated fatty acid. Fatty acids that do not contain double or triple bonds are called saturated fatty acids. Examples of saturated fatty acids include butyric acid (C4: 0), caproic acid (C6: 0), caprylic acid (C8: 0), capric acid (C10: 0), lauric acid (C12: 0), myristic acid (C14). : 0), palmitic acid (C16: 0), stearic acid (C18: 0), isostearic acid (C18: 0), 12-hydroxystearic acid (C18: 0), ricinoleic acid (C18: 0), arachidic acid ( C20: 0), behenic acid (C22: 0), lignoceric acid (C24: 0), serotic acid (C26: 0), montanic acid (C28: 0), melicic acid (C30: 0), and the like. The saturated fatty acid is preferably butyric acid (C4: 0), caproic acid (C6: 0), caprylic acid (C8: 0), capric acid (C10: 0), lauric acid (C12: 0), myristic acid (C14: 0), palmitic acid (C16: 0), stearic acid (C18: 0), arachidic acid (C20: 0) and behenic acid (C22: 0). Fatty acids containing double bonds are called unsaturated fatty acids. Examples of unsaturated fatty acids include myristoleic acid (C14: 1), palmitooleic acid (C16: 1), oleic acid (C18: 1), linoleic acid (C18: 2), linolenic acid (C18: 3) Γ-linolenic acid (C18: 3), eicosenoic acid (C20: 1), dihomo-γ-linolenic acid (C20: 3), arachidonic acid (C20: 4), eicosapentaenoic acid (C20: 5), erucic acid (C22: 1), docosapentaenoic acid (C22: 5), docosahexaenoic acid (C22: 6), and the like. The unsaturated fatty acid is preferably selected from the group consisting of oleic acid (C18: 1), linoleic acid (C18: 2), linolenic acid (C18: 3) and γ-linolenic acid (C18: 3). The fatty acid is preferably myristic acid (C14: 0) or oleic acid (C18: 1).

  From the viewpoint of dispersion stability, the fatty acid is preferably lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, or condensed ricinoleic acid, and more preferably myristic acid, palmitic acid, stearic acid, or oleic acid.

  The esterification degree of the polyglyceric acid fatty acid ester is not particularly limited, but those having a high monoester content and a low esterification degree are preferred.

(1.2.2 Enzymatic degradation lecithin)
The “enzymatically decomposed lecithin” used in the present invention refers to a product obtained by subjecting only the fatty acid ester portion of a phospholipid mixture containing lecithin as a main component to limited hydrolysis with phospholipase. When the enzymatically degraded lecithin is used in the present invention, an enzymatically decomposed lecithin consisting only of a phospholipase degradation product of lecithin may be used, including not only a phospholipase degradation product of lecithin but also a phospholipase degradation product of various phospholipids. Mixtures may be used. The enzyme-degraded lecithin may be purified by any purification method after degradation with phospholipase. The enzyme-decomposed lecithin may also be based on phosphatidic acid and lysolecithin obtained from the enzyme-degraded lecithin described in the existing additive list, that is, plant lecithin or egg yolk lecithin. In the list of existing additives, “plant lecithin” refers to a substance based on lecithin obtained from rape or soybean seeds. In the list of existing additives, “egg yolk lecithin” refers to a substance mainly composed of lecithin obtained from egg yolk.

  “Lecithin” in the narrow sense refers to a phospholipid, that is, phosphatidylcholine that generates two fatty acid molecules, one glycerophosphate molecule, and one choline molecule by hydrolysis. Lecithin may also consist of a fatty acid residue and a phosphate group in the glycerin skeleton, a basic compound bonded to it, or a sugar. When lecithin is to be used in the present invention, pure lecithin may be used or a mixture based on lecithin may be used. In the present specification, the “main component” means that the component is preferably about 5% by weight or more of the composition, more preferably about 10% by weight or more, further preferably about 15% by weight or more, most preferably It means to occupy about 20% by weight or more.

  All the enzymatically degraded lecithins have a phosphate group in the hydrophilic group portion. Therefore, enzymatically decomposed lecithin has an extremely strong adsorption covering power on the surface of poorly water-soluble organic compounds such as plant sterols such as hesperetin, as compared with nonionic surfactants such as sucrose fatty acid esters and glycerin fatty acid esters. Therefore, when enzymatically decomposed lecithin is used, a stable adsorption interface layer is formed on the surface of hesperetin, and it is possible to effectively suppress secondary aggregation without peeling even when subjected to heat treatment. Good dispersibility can be obtained.

  As the enzymatically decomposed lecithin used in the present invention, those produced from plant-derived lecithin such as soybean and rapeseed and those produced from animal-derived lecithin such as chicken egg can be used.

  Examples of the enzymatically degraded lecithin that can be used in the present invention include those obtained by hydrolyzing plant lecithin or egg yolk lecithin with phospholipase A or phospholipase D. Examples of such enzymatically degraded lecithins include monoacylglycerophospholipid mixtures based on lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylinositol and lysophosphatidylserine, and phosphatidic acid, lysophosphatidic acid, phosphatidylglycerol and An example is lysophosphatidylglycerol. Among them, lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine are preferable, and lysophosphatidylcholine is more preferable.

  The phospholipase used for the enzymatic degradation of lecithin may be any having phospholipase A and / or D activity. The phospholipase may have any phospholipase activity, such as animal origin such as porcine pancreas, plant origin such as cabbage, and microbial origin such as mold.

  The degradation rate of the enzymatically degraded lecithin is not particularly limited. The decomposition rate can be appropriately adjusted depending on the purpose of use. For the purpose of suppressing secondary aggregation of hesperetin, the degradation rate of the enzymatically degraded lecithin is preferably about 20% to about 95%, more preferably about 30% to about 80%. The degradation rate of enzyme-degraded lecithin can be measured by any method known in the art. For example, the decomposition rate can be determined by measuring the ratio of phosphatidylcholine and lysophosphatidylcholine by HPLC or the like.

  In this specification, “decomposition rate of enzyme-decomposed lecithin” is obtained by dividing the total number of moles of free hydroxyl groups on the glycerin skeleton in the enzyme-decomposed lecithin by three times the total number of moles of glycerin skeleton and multiplying by 100. Is calculated by

(1.2.3 Glycerin fatty acid organic acid ester)
The “glycerin fatty acid organic acid ester” used in the present invention means an ester bond of a fatty acid and an organic acid other than the fatty acid to the glycerin skeleton. The glycerin fatty acid organic acid ester is usually obtained by an ester reaction of an organic acid and a fatty acid monoglyceride. Examples of organic acids that can be used to form glycerin fatty acid organic acid esters include acetic acid, lactic acid, diacetyltartaric acid, citric acid, succinic acid, and the like. From the viewpoint of the stability of hesperetin in an aqueous solution, citric acid and succinic acid are preferred.

As the fatty acid used for forming the glycerin fatty acid organic acid ester, the saturated or unsaturated fatty acid having 6 to 22 carbon atoms described in detail in the above “1.2.1 Polyglycerin fatty acid ester” can be used.

(1.3 Polysaccharides)
When the dispersion of the present invention further contains a polysaccharide, it becomes a more stable dispersion. Examples of polysaccharides used for such purposes include alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth gum, karaya gum and pectin. The polysaccharide is preferably an alginate. A polysaccharide may be used independently and may be used in combination of 2 or more type. Among the polysaccharides, alginic acid and alginic acid ester which is a derivative of alginic acid can be particularly preferably used for stabilizing the dispersion of the present invention, and further, those obtained by esterifying alginic acid with propylene glycol are most suitable for the dispersion of the present invention. It can be suitably used. The degree of esterification of the alginate is preferably about 75% or more, and most preferably about 80% or more.

  The blending ratio of the polysaccharide in the dispersion is not particularly limited. If the blending amount is too small, the dispersion stability of the dispersion may be lowered. If the blending amount is too large, the viscosity of the dispersion becomes extremely high, which may hinder the handling. The blending amount of the polysaccharide in the dispersion is preferably about 0.1% by weight or more, more preferably about 0.5% by weight or more. The blending amount of the polysaccharide in the dispersion is preferably about 5% by weight or less, more preferably about 1% by weight or less.

(1.4 Solvent)
The solvent used in the hesperetin dispersion of the present invention can be any solvent. The solvent is preferably water or any organic solvent miscible with water, more preferably water or ethanol, most preferably water. You may mix and use water and an organic solvent.

  When water and an organic solvent are mixed, the proportion of water in the total solvent is preferably about 50% by volume or more, preferably about 60% by volume or more, and about 70% by volume or more. Preferably about 80% by volume or more, preferably about 90% by volume or more, and most preferably about 95% by volume or more. The organic solvent mixed with water may be one type or two or more types. In consideration of the influence on the environment and the human body, the solvent is preferably water or mainly composed of water. The term “mainly consisting of water” means that about 80% by volume or more of the solvent is water.

  The dispersion of the present invention preferably has a low viscosity to facilitate handling.

(1.5 Dispersion medium used when producing hesperetin particles)
The hesperetin dispersion of the present invention preferably uses a wet pulverization apparatus as described later at the time of production. In order to perform the treatment by the wet pulverizer, a dispersion medium for dispersing the above-described raw materials is required. The dispersion medium can be any dispersion medium. The dispersion medium is preferably water or any organic solvent miscible with water, more preferably water or ethanol, most preferably water. You may mix and use water and an organic solvent.

  When water and an organic solvent are mixed, the proportion of water in the entire dispersion medium is preferably about 50% by volume or more, preferably about 60% by volume or more, and about 70% by volume or more. Preferably, it is about 80% by volume or more, preferably about 90% by volume or more, and most preferably about 95% by volume or more. The organic solvent mixed with water may be one type or two or more types. In consideration of the influence on the environment and the influence on the human body, the dispersion medium is preferably water or mainly composed of water.

  These dispersion media may be evaporated after the production of the hesperetin particles and before the production of the hesperetin dispersion, or may be used as a solvent for the hesperetin dispersion as it is.

  In consideration of industrial safety, it is desirable to add polyhydric alcohol or liquid sugar capable of preventing the growth of bacteria as a preservative to the dispersion medium. Examples of preservatives that can be used for this purpose include propylene glycol, glycerin, diglycerin, triglycerin, polyglycerin, sorbitol, xylitol, maltitol, lactitol, sorbitan, xylose, arabinose, mannose, lactose, sugar, coupling sugar Glucose, enzyme starch syrup, acid saccharified starch syrup, maltose starch syrup, maltose, isomerized sugar, fructose, reduced maltose starch syrup, reduced starch sugar syrup, honey, fructose glucose liquid sugar, and aqueous solutions thereof. These preservatives may be used alone or in combination of two or more. Among these preservatives, glycerin, reduced starch sugar starch syrup, and fructose glucose liquid sugar can be suitably used from the viewpoint of ease of preparation and stability of the hesperetin dispersion.

(1.6 Other materials)
The dispersion of the present invention may contain other materials as needed, as long as the effects of the above-described materials are not hindered, in order to further increase the value of the present invention. In order to stabilize the quality of the dispersion of the present invention, an antioxidant such as tea extract, catechin, and tocopherol may be included.

(2. Method for producing hesperetin dispersion)
The method for preparing the hesperetin dispersion of the present invention is not particularly limited. Preferably, the hesperetin dispersion of the present invention comprises a step of obtaining a mixture by mixing hesperetin bulk powder, a surfactant and a solvent; It is manufactured by a method including a step of grinding a hesperetin powder in the mixture by a grinder to obtain a hesperetin dispersion.

  When the hesperetin dispersion contains a polysaccharide, the hesperetin dispersion of the present invention can be prepared, for example, by the following steps. First, a surfactant is added to a solvent and, if necessary, an antiseptic (for example, glycerin, liquid sugar, etc.) and heated to about 70 ° C. or higher to be well dispersed. Subsequently, the powdered hesperetin powder and polysaccharide are added to the surfactant dispersion to obtain a mixture. This mixture is pulverized by a wet grinder to obtain a hesperetin dispersion. In this process, when hesperetin bulk powder is subjected to a shearing force with a wet grinder, the surfactant is quickly adsorbed on the exposed surface newly appearing on the surface of hesperetin, which inhibits aggregation of hesperetin particles. Desirable for. Therefore, it is preferable that hesperetin and a surfactant coexist in the wet grinding process.

  The apparatus used for manufacturing the hesperetin dispersion of the present invention is not particularly limited. In order to make hesperetin fine particles, it is desirable to use a wet grinder. The wet grinding machine uses glass beads, alumina beads, zirconia beads, titania beads, etc. as the grinding media, and the grinding media collide with each other by rotating the disk or rotor in the grinding chamber (Bessel container). This is a machine for generating a shearing force on the slurry to be crushed and pulverizing the solid content in the slurry. Examples of the grinding media preferably used in the present invention include alumina beads, zirconia beads, and titania beads.

  The particle size of the grinding medium is not particularly limited. The particle size of the grinding media is preferably about 1 mm or less, more preferably about 0.8 mm or less, and even more preferably about 0.5 mm or less. The filling rate of the grinding medium in the grinding chamber is not particularly limited. The filling rate of the grinding medium is usually about 50% or more with respect to the effective volume of the grinding chamber, preferably about 70% or more, and more preferably about 80% or more from the grinding efficiency.

  The wet grinder used in the present invention is not particularly limited. Examples of the wet grinder include those generally called a coball mill, a dyno mill, a sand mill, a ready mill and the like. The wet grinder used in the present invention may be any type such as a vertical type, a horizontal type, a batch type, and a continuous type. From the viewpoint of production efficiency, a continuous wet grinder is recommended. The material of the grinding chamber can be any material, but it is desirable that the grinding chamber is made of ceramic rather than metal so that extraneous foreign matter is not mixed.

(3. Hesperetin dispersion)
The hesperetin dispersion of the present invention contains hesperetin particles, a surfactant and a solvent. The hesperetin dispersion of the present invention is designed so that hesperetin can be easily and stably dispersed in water and is easy to handle. The hesperetin particles, the surfactant and the solvent used in the hesperetin dispersion of the present invention are as described in 1 above. The hesperetin dispersion of the present invention is preferably a dispersion produced according to the above-mentioned “2. Method for producing hesperetin dispersion”. The hesperetin dispersion of the present invention may be a dispersion prepared by redispersing the hesperetin-containing powder of the present invention in a solvent (for example, water).

  In the hesperetin dispersion of the present invention, hesperetin is stably dispersed. “Hesperetin is stably dispersed” means that when the hesperetin dispersion is allowed to stand at room temperature (preferably about 20 ° C.) for at least 24 hours, substantially no precipitation due to hesperetin is observed.

  In the hesperetin dispersion of the present invention, substantially no precipitation is observed after standing for 24 hours. The dispersion of the present invention is preferably allowed to stand after 36 hours, more preferably after 3 days, more preferably after 4 days, still more preferably after 5 days, and particularly preferably for 6 days. Substantially no precipitation is observed after standing, more preferably after standing for 7 days, more preferably after standing for 2 weeks, particularly preferably after standing for 3 weeks, most preferably after standing for 1 month.

  Preferably, in the hesperetin dispersion of the present invention, substantially no precipitation is observed after standing for 24 hours after sterilization by heating in 90 ° C. hot water for 10 minutes, more preferably after standing for 36 hours. After 3 days, more preferably after 4 days, particularly preferably after 5 days, more preferably after 6 days, even more preferably after 7 days, still more preferably 2 Substantially no precipitation is observed after standing for a week, particularly preferably after standing for 3 weeks, most preferably after standing for 1 month.

  “Substantially no precipitation” means that no precipitation is observed at all, or very little, if any, is observed with the naked eye. The amount of precipitation is preferably no more than about 10%, more preferably no more than about 1%, and even more preferably no more than about 0.1% by weight of the amount of hesperitin contained in the hesperetin dispersion. Particularly preferably, it is about 0.05% by weight or less, and most preferably about 0.01% by weight or less.

  The hesperetin dispersion is milky white unless a coloring substance or the like is added. When the dispersion is insufficiently dispersed, the coloration of the dispersion at the top becomes light when left standing for a long time, becomes transparent when severe, and the color of the dispersion at the bottom becomes deep. On the other hand, since the hesperetin dispersion of the present invention is stable, the coloration remains substantially uniform even after standing for a long time. The dispersion of the present invention is allowed to stand for 24 hours, preferably 36 hours, more preferably 3 days, still more preferably 4 days, still more preferably 5 days. Most preferably after 6 days, more preferably after 7 days, even more preferably after 2 weeks, particularly preferably after 3 weeks, most preferably after 1 month. The color is substantially homogeneous.

  Preferably, the hesperetin dispersion of the present invention is substantially uniform in color even after being sterilized by heating for 10 minutes in hot water at 90 ° C. and then allowed to stand for 24 hours, more preferably still for 36 hours. After standing, more preferably after 3 days, still more preferably after 4 days, particularly preferably after 5 days, more preferably after 6 days, more preferably after 7 days, Even more preferably, the coloration is substantially uniform even when observed after standing for 2 weeks, particularly preferably after standing for 3 weeks, and most preferably after standing for 1 month.

  “The coloration is substantially homogeneous” means that the coloration at the top and the coloration at the bottom of the dispersion cannot be distinguished with the naked eye.

  The content of hesperetin particles in the hesperetin dispersion is preferably about 1% by weight or more, more preferably about 3% by weight or more, and further preferably about 5% by weight or more. When the hesperetin dispersion is produced as a stock solution for producing a more dilute hesperetin dispersion, the content of the hesperetin particles in the concentrated hesperetin dispersion is, for example, about 10% by weight or more and about 15% by weight. More than about 20% by weight, about 25% by weight or more, about 30% by weight or more, about 35% by weight or more, about 40% by weight or more, about 45% by weight or more.

  There is no particular upper limit to the content of hesperetin particles in the hesperetin dispersion. For example, it may be about 50% or less, about 45% or less, about 40% or less, about 35% or less, about 30% or less, about 20% or less, about 10% or less, and the like.

  The amount of water in the hesperetin dispersion is preferably about 90% by weight or less, more preferably about 80% by weight or less, still more preferably about 70% by weight or less, particularly preferably about 60% by weight or less. And most preferably not more than about 50% by weight. When the hesperetin dispersion is produced as a stock solution for producing a more dilute hesperetin dispersion, the amount of water in the concentrated hesperetin dispersion is, for example, about 50% by weight or less, about 40% by weight or less, It may be about 30 wt% or less, about 20 wt% or less, about 10 wt% or less.

  There is no particular lower limit to the amount of water in the hesperetin dispersion. For example, it may be about 5% or more, about 10% or more, about 15% or more, about 20% or more, about 30% or more, about 50% or more, and the like.

  The hesperetin dispersion of the present invention is liquid when the solid content is low. The hesperetin dispersion of the present invention exhibits a slurry form when the solid content is large. A stable hesperetin dispersion can also be obtained when the slurry-like hesperetin dispersion of the present invention is diluted with a solvent such as water.

  The hesperetin contained in the hesperetin dispersion of the present invention is very fine particles. The finer the particle size of the hesperetin particles, the higher the dispersion stability. Since the hesperetin dispersion of the present invention is very concentrated and the particle size may not be measured as it is, in such a case, the hesperetin dispersion of the present invention is diluted with water to produce a more dilute dispersion, The particle size in the diluted dispersion is measured. For example, when the hesperetin dispersion of the present invention is diluted with water and the particle size in water is measured with, for example, a wet particle size distribution meter manufactured by Beckman Coulter, the average particle size is 10 μm or less, preferably 1 μm or less. Is desirable.

  In the hesperetin dispersion of the present invention, a film of a surfactant (for example, polyglycerin fatty acid ester, glycerin fatty acid organic acid ester, enzyme-degraded lecithin) and a stabilizer (for example, polysaccharide) is formed around the fine hesperetin powder. By forming, it is considered that a stable dispersion state is maintained. A dispersion model diagram of such a hesperetin preparation is shown in FIG. A normal hesperetin dispersion is schematically shown on the left side of FIG. The hesperetin dispersion of the present invention (shown as “hesperetin preparation”) is schematically shown on the right side of FIG. Furthermore, the structure in which a film is formed around this hesperetin is maintained in the powder, food and drink, quasi drug, pharmaceutical product, external preparation for skin, bath preparation, pet food, fiber, clothing, etc. of the present invention. it is conceivable that. Therefore, it is thought that the effect superior to the conventional hesperetin is exhibited also in these.

  The hesperetin dispersion of the present invention may be used as it is as a food or drink, or may be used as a stock solution for producing a more diluted hesperetin dispersion or food or drink.

(4. Method for producing powder containing hesperetin particles and surfactant)
The method for producing a powder containing the hesperetin particles and the surfactant of the present invention comprises a step of mixing a hesperetin bulk powder, a surfactant and a solvent to obtain a mixture; the mixture is subjected to a wet grinder and the hesperetin raw material in the mixture is obtained. Pulverizing the powder to obtain a hesperetin dispersion; and drying the hesperetin dispersion to obtain a hesperetin powder.

  Regarding the step of obtaining a mixture by mixing hesperetin bulk powder, a surfactant and a solvent, and the step of pulverizing the hesperetin powder powder in the mixture by subjecting the mixture to a wet grinder to obtain a hesperetin dispersion, 2. As described in “Method for producing hesperetin dispersion”.

  The hesperetin powder is obtained by drying the thus obtained hesperetin dispersion. This drying can be performed by any method known in the art. Examples of the drying method include spray drying, freeze drying, vacuum drying, drum drying and the like. Spray drying is preferred.

(5. Powder containing hesperetin particles and surfactant)
The powder of the present invention is a powder containing hesperetin particles and a surfactant. The hesperetin particles and the surfactant used in the powder of the present invention are as described in 1 above. Furthermore, the powder of the present invention may contain other substances such as polysaccharides and antioxidants as described in 1 above.

  The content of hesperetin particles in the powder of the present invention is preferably about 30% by weight or more, more preferably about 40% by weight or more, and further preferably about 50% by weight or more. There is no particular upper limit to the content of hesperetin particles in the powder of the present invention. For example, it may be about 95% or less, about 90% or less, about 80% or less, about 70% or less, about 60% or less, about 50% or less, and the like.

  A stable hesperetin dispersion can be easily obtained by adding the powder of the present invention to water and mixing.

  When the powder of the present invention is ingested, the powder of the present invention exhibits a significantly superior effect than the conventional hesperetin powder.

(6. Food and drink containing hesperetin particles and surfactant)
The food and drink of the present invention contains hesperetin particles and a surfactant. The hesperetin particles and the surfactant used in the food and drink of the present invention are as described in 1 above. Furthermore, the food and drink of the present invention may also contain other substances such as polysaccharides and antioxidants as described in 1 above.

  The food and drink of the present invention may be any food or drink. The food and drink may be solid, semi-solid, or liquid, but is preferably liquid. The food or drink is preferably a health food, more preferably a health drink, but is not limited thereto. The health food can be used for the same normal use as the hesperetin contained in the health food. Examples of uses and effects of health foods include blood flow improvement and cooling improvement, skin condition improvement, cholesterol lowering, allergy symptom improvement, and anti-inflammatory use. It can be confirmed according to a method known in the art that the food or drink of the present invention has such an effect. When ingested, the food and drink of the present invention exhibits a significantly superior effect than conventional hesperetin-containing food and drink.

  Examples of foods and drinks include, for example, instant foods (eg, instant noodles, cup noodles, retort foods, cooked foods, cooked cans, foods for microwave ovens, instant soups, instant stews, instant miso soup, Instant soup, canned soup, freeze-dried food); beverages (for example, carbonated drinks (cider, ramune, etc.), natural fruit juice, fruit juice drinks, soft drinks, soft drinks with fruit juices, fruit drinks, fruit foods with fruit granules, Vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutrition drinks, alcoholic drinks, condiment drinks; flour foods (eg bread, macaroni, spaghetti, noodles, cake mix, Fried flour, bread crumbs, gyoza peel, spring roll peel); noodles other than flour food (eg, buckwheat); confectionery (eg, Western confectionery (eg, Caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, castella, pie, snacks, crackers), Japanese confectionery (eg, nerikiri, red bean paste, gourd, bun), rice confectionery (eg, rice cracker, hail, rice cake), beans Confectionery, dessert confectionery (for example, apricot tofu, jelly, agar), tablet confectionery; frozen confectionery (for example, ice milk, ice confectionery); basic seasonings (for example, soy sauce, miso, sauces, tomato processed seasonings, mirins, Vinegars, sweeteners, fish sauce, nyocumam); complex seasonings (eg flavor seasonings, cooking mix, curry sauce, sauces, dressing, noodle soup, spices); fat foods (eg butter, margarine, mayonnaise) ); Milk and dairy products (eg, milk, processed milk, milk drinks, yogurts, lactic acid bacteria drinks, butter, margarine) Cheese, whipped cream, ice cream, prepared milk powder, cream); frozen food (for example, frozen raw material, semi-cooked frozen food, cooked frozen food); processed fishery products (for example, canned fish, paste, fish ham, fish meat) Sausages, marine products (for example, salmon, chikuwa), marine delicacy, marine dried products, boiled fish); livestock processed products (for example, canned livestock, livestock paste, livestock ham, livestock sausages, livestock delicacy); agricultural processed products (For example, canned agricultural products, canned fruits, jam, marmalade, fruit sauce, pickles, boiled beans, dried agricultural products, cereals); baby food, baby food; sprinkles, tea pickles; supplements, drinks.

  The content of hesperetin particles in the food and drink of the present invention is preferably about 0.01% by weight or more, more preferably about 0.05% by weight or more, and further preferably about 0.1% by weight or more. More preferably about 0.3% by weight or more, still more preferably about 0.5% by weight or more. The content of the hesperetin particles in the food and drink of the present invention is, for example, about 1% by weight or more, about 3% by weight or more, about 5% by weight or more, about 10% by weight or more, about 15% by weight or more, about 20% by weight. More than about 25% by weight, about 30% by weight or more, about 35% by weight or more, about 40% by weight or more, about 45% by weight or more.

  There is no particular upper limit to the content of hesperetin particles in the food and drink of the present invention. The content of hesperetin particles in the food and drink of the present invention is, for example, about 90% by weight or less, about 85% by weight or less, about 80% by weight or less, about 70% by weight or less, about 60% by weight or less, about 50% by weight. Hereinafter, it may be about 45 wt% or less, about 40 wt% or less, about 35 wt% or less, about 30 wt% or less, about 20 wt% or less, about 10 wt% or less.

  If the daily intake of hesperetin is sufficient to obtain the desired effect, the content of hesperetin particles in the food and drink and the intake of food and drink per day can be appropriately set. The daily intake of hesperetin is preferably about 0.1 mg / kg (body weight) or more, more preferably about 0.5 mg / kg (body weight) or more, more preferably about 1 mg / kg (body weight) or more. And most preferably about 5 mg / kg (body weight) or more. In certain embodiments, for example, 10 mg / kg (body weight) or more, 20 mg / kg (body weight) or more, 30 mg / kg (body weight) or more, 40 mg / kg (body weight) or more, or 50 mg / kg (body weight) or more. Also good. The daily intake of hesperetin is preferably about 200 mg / kg (body weight) or less, more preferably about 150 mg / kg (body weight) or less, more preferably about 100 mg / kg (body weight) or less, Preferably it is about 50 mg / kg (body weight) or less. In certain embodiments, for example, 40 mg / kg (body weight) or less, 30 mg / kg (body weight) or less, 20 mg / kg (body weight) or less, 10 mg / kg (body weight) or less, or 5 mg / kg (body weight) or less. Also good.

  No special process is required to produce the food or drink of the present invention, and the hesperetin particles and the surfactant, or the hesperetin dispersion or powder of the present invention is added together with the raw material of the food or drink at the initial stage of the food or drink production process. Or added during the manufacturing process or at the end of the manufacturing process. It is preferable to produce the food or drink of the present invention using the hesperetin dispersion or the hesperetin-containing powder of the present invention. As the addition method, a normal method such as mixing, kneading, dissolution, dipping, spraying, spraying, and application is selected according to the type and properties of the food and drink. The food and drink of the present invention can be prepared according to methods known to those skilled in the art.

  By incorporating the hesperetin dispersion liquid or hesperetin powder of the present invention into food or drink, food or drink effective for prevention and treatment of wrinkles, stains, buckwheat, pigmentation and the like can be obtained. The food and drink of the present invention also enhances skin moisture retention and is effective in improving symptoms such as dry skin, rough skin, allergies, and atopic dermatitis. The food and drink of the present invention is also effective for improving the skin elasticity. The food and drink of the present invention can also exert an effect of restoring body temperature by promoting blood flow.

(7. Use of hesperetin dispersion and powder of the present invention)
The hesperetin dispersion and powder of the present invention can be widely used in foods and drinks, quasi drugs, pharmaceuticals, external preparations for skin, bath preparations, feeds, pet foods, fibers, clothes and the like. Applications of the hesperetin dispersion and the powder of the present invention are not limited to these.

  Preferable specific examples of the food and drink that can utilize the hesperetin dispersion and powder of the present invention are, for example, the food and drink described in “6. Food and drink containing hesperetin particles and a surfactant”.

  The hesperetin dispersion of the present invention is particularly suitable for use in foods and drinks stored for a long time. The storage period of the food and drink in which the hesperetin dispersion is used is preferably about 1 week or more, more preferably about 2 weeks or more, still more preferably about 1 month or more, and particularly preferably about 3 months or more. Yes, most preferably about 6 months or more. There is no particular upper limit to the shelf life of foods and drinks in which hesperetin dispersion is used, for example, about 5 years or less, about 3 years or less, about 2 years or less, about 1 year or less, about 6 months or less, about 3 months or less, etc. It can be.

  In particular, the powder of the present invention is stored for a short period of time after the dispersion is prepared, and is intended to be consumed thereafter (for example, a powdered beverage), used for a product with a relatively short expiration date (for example, a milk beverage) Suitable for chilled products). There is no particular lower limit to the shelf life of the food and drink in which the powder of the present invention is used, for example, about 12 hours or more, about 1 day or more, about 2 days or more, about 3 days or more, about 4 days or more, about 5 days or more. And so on. The storage period of foods and drinks in which the powder of the present invention is used is preferably about 2 weeks or less, more preferably about 10 days or less, and further preferably about 1 week or less.

(7.1 Quasi-drugs and pharmaceuticals)
The quasi drugs and pharmaceuticals that can utilize the hesperetin dispersion and powder of the present invention can be any quasi drugs and pharmaceuticals. The quasi-drug and pharmaceutical product of the present invention include hesperetin particles and a surfactant. The hesperetin particles and the surfactant used in the quasi-drug and pharmaceutical product of the present invention are as described in 1 above. Furthermore, the quasi-drug and the pharmaceutical of the present invention may also contain other substances such as polysaccharides and antioxidants as described in 1 above. In the quasi-drug and pharmaceutical product of the present invention, the hesperetin particles are preferably blended as an active ingredient.

  The quasi-drug and pharmaceutical of the present invention may be solid, semi-solid, or liquid. The quasi drug and pharmaceutical product of the present invention are preferably liquid.

  Examples of quasi drugs and pharmaceutical dosage forms of the present invention that can be administered by oral administration or parenteral administration (for example, intravascular administration and transdermal administration) include: Examples thereof include powders, powders, tablets, capsules, pills, suppositories, liquids, and injections.

  When the quasi-drug and pharmaceutical product of the present invention are for oral administration, the content of hesperetin particles in the quasi-drug and pharmaceutical product of the present invention is preferably 0.01% by weight or more, more preferably Is about 0.1% by weight or more, more preferably about 0.3% by weight or more, and further preferably about 0.5% by weight or more. The content of the hesperetin particles in the quasi-drug and the pharmaceutical of the present invention is, for example, about 1% by weight or more, about 3% by weight or more, about 5% by weight or more, about 10% by weight or more, about 15% by weight or more, It may be about 20% or more, about 25% or more, about 30% or more, about 35% or more, about 40% or more, about 45% or more, and the like. There is no particular upper limit to the content of hesperetin particles in the quasi-drug of the present invention and the pharmaceutical product. The content of hesperetin particles in the quasi-drug and the pharmaceutical of the present invention is, for example, about 90% by weight or less, about 85% by weight or less, about 80% by weight or less, about 70% by weight or less, about 60% by weight or less, It may be about 50% or less, about 45% or less, about 40% or less, about 35% or less, about 30% or less, about 20% or less, about 10% or less, and the like.

  When the quasi-drug and pharmaceutical product of the present invention are for transdermal administration, the content of hesperetin particles in the quasi-drug and pharmaceutical product of the present invention is preferably 0.01% by weight or more, and more Preferably it is about 0.1% by weight or more, more preferably about 0.3% by weight or more, and further preferably about 0.5% by weight or more. The content of the hesperetin particles in the quasi-drug and the pharmaceutical of the present invention is, for example, about 1% by weight or more, about 3% by weight or more, about 5% by weight or more, about 10% by weight or more, about 15% by weight or more, It may be about 20% or more, about 25% or more, about 30% or more, about 35% or more, about 40% or more, about 45% or more, and the like. There is no particular upper limit to the content of hesperetin particles in the quasi-drug of the present invention and the pharmaceutical product. The content of hesperetin particles in the quasi-drug and the pharmaceutical of the present invention is, for example, about 90% by weight or less, about 85% by weight or less, about 80% by weight or less, about 70% by weight or less, about 60% by weight or less, It may be about 50% or less, about 45% or less, about 40% or less, about 35% or less, about 30% or less, about 20% or less, about 10% or less, and the like.

  As long as the daily intake of hesperetin is sufficient to obtain the desired effect, the content of the hesperetin particles in the quasi-drug and the pharmaceutical of the present invention and the intake of the quasi-drug and the pharmaceutical per day The amount can be appropriately set.

  By adding the hesperetin dispersion liquid or hesperetin powder of the present invention to quasi drugs and pharmaceuticals, quasi drugs and pharmaceuticals effective for the prevention and treatment of wrinkles, stains, buckwheat, pigmentation and the like can be obtained. The quasi-drug and pharmaceutical product of the present invention are also effective in improving the moisture retention of the skin and improving symptoms such as dry skin, rough skin, allergies, and atopic dermatitis. The quasi-drug and pharmaceutical product of the present invention are also effective for improving skin elasticity. The quasi-drug and pharmaceutical product of the present invention can also exert an action of restoring body temperature by promoting blood flow.

  When quasi drugs and pharmaceuticals are to be administered orally, the daily intake of hesperetin is preferably about 0.1 mg / kg (body weight) or more, more preferably about 0.5 mg / kg (body weight). ) Or more, more preferably about 1 mg / kg (body weight) or more, and most preferably about 5 mg / kg (body weight) or more. In certain embodiments, for example, 10 mg / kg (body weight) or more, 20 mg / kg (body weight) or more, 30 mg / kg (body weight) or more, 40 mg / kg (body weight) or more, or 50 mg / kg (body weight) or more. May be. The daily intake of hesperetin is preferably about 200 mg / kg (body weight) or less, more preferably about 100 mg / kg (body weight) or less, more preferably about 150 mg / kg (body weight) or less, Preferably it is about 50 mg / kg (body weight) or less. In certain embodiments, for example, 40 mg / kg (body weight) or less, 30 mg / kg (body weight) or less, 20 mg / kg (body weight) or less, 10 mg / kg (body weight) or less, or 5 mg / kg (body weight) or less. Also good.

  When quasi-drugs and pharmaceuticals are to be administered transdermally, the amount of hesperetin applied per day is preferably about 2 μg or more, more preferably about 3 μg or more, and even more preferably about 5 μg (body weight). More preferably, it is about 10 μg or more. The amount of hesperetin applied per day is preferably about 200 mg or less, more preferably about 150 mg or less, still more preferably about 100 mg or less, and most preferably about 50 mg or less. In certain embodiments, for example, it may be 40 mg or less, 30 mg or less, 20 mg or less, 10 mg or less, or 5 mg or less.

(7.2 External preparation for skin)
The hesperetin dispersion and powder of the present invention are preferably used for a skin external preparation.

  In the present specification, the term “skin external preparation” refers to a preparation used on the skin that achieves a desired effect by being brought into contact with the skin. In particular, the present invention is effective for applications that continuously contact the skin for a long period of time (for example, applications that continuously contact the skin for 1 hour or more, or applications that continuously contact the skin for 5 hours or more).

(7.2.1 Types of topical skin preparations)
A preferred example of the external preparation for skin is a cosmetic. Preferable examples of the cosmetic include skin care cosmetics. Specific examples of cosmetics include skin care cosmetics (for example, lotions, emulsions, creams, cosmetics, emollient creams, emollient lotions, cream rinses, cold creams, vanishing creams, lotions, gels, packs (for example, Face pack), hand cream, leg cream, neck cream, body lotion, etc.), cosmetics (eg foundation, makeup base lotion, makeup base cream, eye color, teak color, eye shadow, lipstick, lip balm, blusher, etc. ), Hair cosmetics (hair nourishing agent, hair restorer, hair liquid, hair nick, permanent wave agent, hair color, hair cream, hair lotion, hair treatment, hair pack, etc.), soap, body soap Shampoos, conditioners, rinses, bath salts, face wash, shaving cream, gloss, lip cream, cakes and the like. In particular, the present invention is effective for applications where a moisturizing effect is desired. For example, the present invention is effective for skin care cosmetics. The present invention is particularly effective for an application that makes contact with the skin for a long time, but the present invention is also effective for an application that is washed after being used in a short time, such as a facial cleanser or a shampoo.

  As described above, cosmetics are also included in the cosmetics. Cosmetics include cleansing cosmetics, hair cosmetics, basic cosmetics, makeup cosmetics, aromatic cosmetics, tanning cosmetics, sunscreen cosmetics, nail cosmetics, eyeliner cosmetics, eyeshadow cosmetics, teak, lip cosmetics, oral cosmetics, etc. The present invention is effective for any application.

  By blending the hesperetin dispersion liquid or hesperetin powder of the present invention into the external preparation for skin, an external preparation for skin effective for prevention and treatment of wrinkles, stains, buckwheat, pigmentation and the like can be obtained. The skin external preparation of the present invention also enhances skin moisture retention and is effective in improving symptoms such as dry skin, rough skin, allergies, and atopic dermatitis. The external preparation for skin of the present invention is also effective for improving skin elasticity. The external preparation for skin of the present invention can also exert an action of recovering body temperature by promoting blood flow.

  Examples of dosage forms of the external preparation for skin of the present invention include ointments, thickening gel systems, lotions, water-in-oil emulsions, oil-in-water emulsions, solids, sheets, powders, gels, mousses, and sprays Shape. It may be a product in a form in which a skin external preparation is impregnated into a cloth, such as a make-up pack.

  When the dosage form of the external preparation for skin is lotion, emulsion, thickening gel, etc., plant-based polymers such as gum arabic, gum tragacanth, galactan, guar gum, carrageenan, pectin, quince seed (quince) extract, brown algae powder, Microbial polymers such as xanthan gum, dextran, and bullulan, animal polymers such as collagen, casein, albumin, gelatin, starches such as carboxymethyl starch and methylhydroxy starch, methylcellulose, nitrocellulose, ethylcellulose, methylhydroxypropylcellulose, Celluloses such as hydroxyethyl cellulose, cellulose sulfate, hydroxypropyl cellulose, carboxymethyl cellulose, crystalline cellulose, cellulose powder, polyvinyl alcohol, polyvinyl Vinyl polymers such as ether, polyvinylpyrrolidone and carboxyvinyl polymer, polyacrylic acid and its salts, acrylic polymers such as polyacrylimide, organic thickeners such as glycyrrhizic acid and alginic acid, bentonite, hectorite, labonite It is preferable to add a water-soluble thickener composed of an inorganic thickener such as aluminum magnesium silicate and anhydrous silicic acid and a lower alcohol such as ethanol and isopropanol among the alcohols in order to increase the effect.

(7.2.2. Auxiliary components)
The external preparation for skin of the present invention may contain an auxiliary component in addition to the hesperetin dispersion or the hesperetin powder of the present invention. By using the hesperetin dispersion liquid or hesperetin powder of the present invention in combination with at least one auxiliary component, the skin moisturizing effect in the external preparation for skin is improved, dry skin and rough skin are improved, skin elasticity and elasticity are improved. It can improve or improve the whitening effect. The auxiliary components used in the present invention are described below.

  In addition to the following effects, these auxiliary components also have the effect of enhancing the stability and safety as a drug. As long as any auxiliary component is within the following blending amounts, when used in combination with the hesperetin dispersion or hesperetin powder of the present invention, it does not affect hesperetin in the external preparation for skin and stability over time is also good. High moisturizing effect and whitening effect can be exhibited. It can be increased or decreased depending on the expected effect. In addition, the following auxiliary component can be used in combination of at least 1 type, ie, 1 type, or 2 or more types of substances.

  The auxiliary component is preferably selected from the group consisting of a moisturizing component, a whitening component, a UV absorber, an anti-inflammatory agent, a cell activator and an antioxidant.

(7.2.2.1 Moisturizing ingredients)
In the present specification, the term “moisturizing component” refers to a highly absorbable substance used for the purpose of preventing moisture from drying by giving moisture to skin, hair or the like, or a compound having a collagen-inducing effect.

  Examples of moisturizing ingredients include: ascorbic acid and derivatives thereof, vitamins other than ascorbic acid, derivatives of pyridoxine, derivatives of α-tocopherol, pantothenic acid derivatives, sugars and sugar derivatives, amino acids and derivatives thereof, Polyhydric alcohol, phenol and derivatives thereof, collagens, hydroxycarboxylic acid and salts thereof, hydroxysalicylic acid glycoside, hydroxysalicylic acid aliphatic ester glycoside, hydroxycinnamic acid and derivatives thereof, caffeic acid and derivatives thereof, Herbal extracts, natural extracts, placenta extract, oil-soluble licorice extract, ceramide, ceramide-like structure, crude sugar extract, molasses extract, mycelium culture and its extract, urea, hinokitiol, sulfur, azelain And derivatives thereof, vitamin E-nicotinate and di Isopropyl amine dichloroacetate, deep sea water, and alkaline simple hot spring water.

  Examples of ascorbic acid and its derivatives include ascorbic acid monostearate, ascorbic acid monopalmitate, ascorbic acid monoalkyl esters such as ascorbic acid monooleate, ascorbic acid monophosphate, ascorbic acid such as ascorbic acid-2-sulfate Ascorbic acid such as acid monoester derivatives, ascorbic acid distearate, ascorbic acid dipalmitate, ascorbic acid dioleate, ascorbic acid diester derivatives such as ascorbic acid diphosphate, ascorbic acid tristearate, ascorbic acid tripalmitate, ascorbic acid trioleate Ascorbic acid triester derivatives such as trialkyl esters, ascorbic acid triphosphate, ascorbic acid-2-glucose Such as ascorbic acid glycosides such as de thereof. In particular, L-ascorbic acid is generally referred to as vitamin C, and has a cell respiration action, an enzyme activation action, a collagen formation action due to its strong reduction action, and a melanin reduction action. The amount of ascorbic acid and its derivative is preferably about 0.01% by weight or more and not particularly limited, for example, about 10% by weight or less, based on the total amount of the external preparation for skin.

  As vitamins other than ascorbic acid, natural extracts, retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), thiamine hydrochloride, thiamine sulfate (vitamin B1), riboflavin (Vitamin B2), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, ergocalciferol (vitamin D2), Cholecalciferol (vitamin D3), dihydrotaxosterol, vitamin E group: tocopherol and its derivatives, ubiquinones, vitamin K group: phytonadione (vitamin K1), menaquinone (vitamin K2), menadione (vita) Down K3), menadiol (vitamin K4), other essential fatty acids (vitamin F), carnitine, .gamma.-oryzanol, orotic acid, vitamin P such (rutin, eriocitrin, hesperidin), and vitamin U. Desirably, retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), pyridoxine, ubiquinones, vitamin K group: phytonadione (vitamin K1), menaquinone (vitamin K2), hesperidin (Vitamin P) and its derivatives (eg, α-glucosyl-hesperidin). One or more of these vitamins can be appropriately selected and blended. The amount of vitamins other than ascorbic acid is not uniformly determined, but is preferably about 0.001% by weight or more, preferably about 10.0% by weight or less, based on the total amount of the external preparation for skin.

  Examples of the pyridoxine derivative include pyridoxal, pyridoxamine, pyridoxine-5'-phosphate pyridoxal-5'-phosphate, pyridoxamine-5'-phosphate, pyridoxal phosphate, pyridoxine acid and the like. The amount of the pyridoxine derivative is preferably about 0.001% by weight or more, more preferably about 0.01% by weight or more, based on the total amount of the external preparation for skin. The compounding amount of the pyridoxine derivative is preferably about 5% by weight or less, more preferably about 3% by weight or less based on the total amount of the external preparation for skin.

  Examples of the α-tocopherol derivative include α-tocopheryl retinoate which is an ester of vitamin E acid. In this case, α-tocopherol is DL-α-tocopherol, D-α-tocopherol, or natural mixed tocopherol containing D-α-tocopherol, and vitamin A acid is retinoic acid (all-trans-retinoic acid), 13 -Cis-retinoic acid, 11-cis-retinoic acid, 9-cis-retinoic acid, or mixed isomers thereof, and particularly an ester of DL-α-tocopherol and all-trans-retinoic acid is preferable.

  Examples of pantothenic acid derivatives include panthetin-S-sulfonic acid, 4'-phosphopantetin-S-sulfonic acid, panthetin, glucopyranosyl pantothenic acid, and the like. These can be used not only in free acid but also in salt form. Examples of the salt include organic acid salts and inorganic acid salts, and alkali metal salts and alkaline earth metal salts are preferable. The compounding amount of the pantothenic acid derivative is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The compounding amount of the pantothenic acid derivative is preferably about 5% by weight or less, more preferably about 3% by weight or less based on the total amount of the external preparation for skin.

  Examples of sugars and sugar derivatives include maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, amylolytic sugar, maltose, xylitol, amylolytic sugar reducing alcohol, D-glyceryl aldehyde, dihydroxyacetone, D-erythrose , D-erythrulose, D-treose, erythritol, etc.), L-arabinose, D-xylose, L-lyxose, D-arabinose, D-ribose, D-ribulose, D-xylulose, L-xylulose, D-glucose, D -Tulose, D-bucose, D-galactose, D-fructose, L-galactose, L-mannose, D-tagatose, aldheptose, heproose, octulose, etc., 2-deoxy-D-ribose, 6-deo Si-L-galactose, 6-deoxy-L-mannose, etc., D-galactosamine, sialic acid, aminouronic acid, muramic acid, etc., D-glucuronic acid, D-mannuronic acid, L-guluronic acid, D-galacturonic acid, L -Iduronic acid, etc., sucrose, gunthianose, umbelliferose, lactose, planteose, isolicnose, α, α-trehalose, raffinose, lycnose, umbilicin, stachyose verbascoses, chitosan and chitosan degradation product, hyaluronic acid, Chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, mucoitin sulfate, caronin sulfate, keratosulfuric acid, heparin, chitin or their salts, mucopolysaccharides, glucosamine, glucosamine-6-phosphate or glucosamine-6- Glucose such as sulfuric acid Min and derivatives thereof. In general, it is known that polysaccharides containing amino acids have the action of smoothing the movement of a living body and covering the surface of cells and tissues from the outside. One or more of these sugars and sugar derivative components are appropriately selected and blended. The blending amount varies depending on the type of sugar and sugar derivative and cannot be determined uniformly. Typically, the blending amount of the sugar and the sugar derivative is about 0.01% by weight or more and about 5% by weight or less in the total amount of the external preparation for skin.

  Amino acids and their derivatives are used to restore hydration to aging or hardened epidermis and are glycine, serine, cystine, alanine, threonine, cysteine, valine, phenylalanine, methionine, leucine, tyrosine, broline, isoleucine, tryptophan And neutral amino acids such as hydroxybroline, acidic amino acids such as aspartic acid, asparagine, glutamine and glutamic acid, and basic amino acids such as arginine, histidine and lysine. Amino acid derivatives include acyl sarcosine and its salts, acyl glutamic acid and its salts, acyl-β-alanine and its salts, glutathione, pyrrolidone carboxylic acid and its salts, as well as glutatin, carnosine, gram cigin S, tyrosidine A, tyrosidine B Oligopeptides such as γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid and salts thereof. If the blending amount of amino acids and derivatives thereof is too small, the heat retention effect on the skin is weak, and if it is too much, not only the improvement of the effect is observed but also it is difficult to prevent amino acid alteration. The amount of amino acids and derivatives thereof is preferably about 0.01% by weight or more, more preferably about 0.05% by weight or more, based on the total amount of the external preparation for skin. The blending amount of amino acids and derivatives thereof is preferably about 20% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  Examples of the polyhydric alcohol include ethylene glycol, trimethylene glycol, tetramethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,2-butylene glycol, 2,3-butylene glycol, and 1,2-pentane. Divalent polyhydric alcohols such as diol, pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol and octylene glycol; 3 such as glycerin, trimethylolpropane and 1,2,6-hexanetriol Tetravalent polyhydric alcohols such as pentaerythritol; pentavalent polyhydric alcohols such as xylitol and fructose; hexavalent polyhydric alcohols such as sorbitol and mannitol. Polyhydric alcohols such as amylolytic sugar reducing alcohol; polyhydric alcohol polymers such as diethylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, polyglycerin; POE-tetra Hydrofurfuryl alcohol, POP-butyl ether, POP / POE-butyl ether, tripolyoxypropylene glycerin ether, POP-glycerin ether, POP / POE-diglycerin ether, POP-glycerin ether phosphate, POP / POE-pentaerythritol ether, etc. Examples include polyalkylene oxide ethers. The blending amount of the polyhydric alcohol is preferably about 0.01% by weight or more based on the total amount of the external preparation for skin. The blending amount of the polyhydric alcohol is not particularly limited, but is preferably about 10% by weight or less.

  Phenol and its derivatives include hydroquinone glycoside, hydroquinone monoethyl ether, hydroquinone mono n-propyl ether, hydroquinone mono n-butyl ether, hydroquinone mono n-hexadecyl ether, hydroquinone mono n-octadecyl ether, p-ethylphenol, pn-propylphenol, pn-butylphenol, pt-butylphenol, p-isopropylphenol, p-hexadecylphenol, p-octadecylphenol, 4-isopropylcatechol monobutyl ester, 4-isopropylcatechol monoheptadeca Examples include esters. The blending amount of phenol and its derivative is preferably about 0.01% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The blending amount of phenol and its derivative is preferably about 20% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  Collagens include extracted collagen such as mammalian skin, tendons, bones, blood vessels, connective tissue, collagen fiber types, fish collagen (skin, scale extract), soluble collagen, hydrolyzed collagen solution, hydrolyzed collagen ethyl, hydrolyzed collagen Degraded collagen hexadecyl and the like can be mentioned. The blending amount of collagen is preferably about 0.01% by weight or more based on the total amount of the external preparation for skin. There is no particular upper limit to the amount of collagen to be added, but it is preferably 1.0% by weight or less.

  Examples of hydroxycarboxylic acids and salts thereof include glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, salicylic acid, mevalonic acid, and mevalonic acid lactone. Examples of the salts include metal salts such as sodium, potassium, and magnesium, Examples include organic salts such as triethanolamine and 2-amino-methyl-1,3-propanediol. The amount of the hydroxycarboxylic acid and its salt is preferably about 0.0001% by weight or more, more preferably about 0.001% by weight or more, based on the total amount of the external preparation for skin. The amount of the hydroxycarboxylic acid and its salt is preferably about 5% by weight or less, more preferably about 3% by weight or less, based on the total amount of the external preparation for skin.

  Hydroxysalicylic acid glycosides and hydroxysalicylic acid aliphatic ester glycosides are represented by general formulas 1, 2, and 3. These glycosides are produced by reacting hydroxysalicylic acid or hydroxysalicylic acid aliphatic ester with an acetylated sugar such as pentaacetylglucose (or an acetobrominated sugar such as acetobromoglucose) in the presence of an acid catalyst. Can be obtained by: The blending amount of hydroxysalicylic acid glycoside and hydroxysalicylic acid aliphatic ester glycoside is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more in the total amount of the external preparation for skin. . The blending amount of the hydroxysalicylic acid glycoside and the hydroxysalicylic acid aliphatic ester glycoside is preferably about 20% by weight or less, more preferably about 7% by weight or less in the total amount of the external preparation for skin.

In General Formulas 1 to 3, R ¹ is a hydrogen atom, a saturated or unsaturated linear or branched hydrocarbon group having 1 to 20 carbon atoms, and R ² is a sugar residue.

  Specific examples of the glycoside include 3-β-D-glucopyranosyloxysalicylic acid, methyl 3-β-D-glucopyranosyloxysalicylate, ethyl 3-β-D-glucopyranosyloxysalicylate, 3-β-D-glucopyranosyloxysalicylic acid propyl, 3-β-D-glucopyranosyloxysalicylic acid isopropyl, 4-β-D-glucopyranosyloxysalicylic acid, 4-β-D-glucopyrano Methyl siloxysalicylate, ethyl 4-β-D-glucopyranosyloxysalicylate, 4-β-D-glucopyranosyloxysalicylate propyl, 4-β-D-glucopyranosyloxysalicylate isopropyl, 5-β -D-glucopyranosyloxysalicylic acid, methyl 5-β-D-glucopyranosyloxysalicylate, 5-β-D-glucopyranosyl Ethyl cisalicylate, 5-β-D-glucopyranosyloxysalicylic acid propyl, 5-β-D-glucopyranosyloxysalicylic acid isopropyl, 6-β-D-glucopyranosyloxysalicylic acid, 6-β-D -Methyl glucopyranosyloxysalicylate, ethyl 6-β-D-glucopyranosyloxysalicylate, propyl 6-β-D-glucopyranosyloxysalicylate, isopropyl 6-β-D-glucopyranosyloxysalicylate 2-β-D-glucopyranosyloxy-3-hydroxybenzoic acid, 2-β-D-glucopyranosyloxy-3-hydroxybenzoic acid methyl, 2-β-D-glucopyranosyloxy- Ethyl 3-hydroxybenzoate, 2-β-D-glucopyranosyloxy-3-hydroxybenzoate, 2-β-D-glucopi Isopropyl lanosyloxy-3-hydroxybenzoate, 2-β-D-glucopyranosyloxy-4-hydroxybenzoic acid, 2-β-D-glucopyranosyloxy-4-hydroxybenzoic acid methyl, 2-β- D-glucopyranosyloxy-4-hydroxybenzoate ethyl, 2-β-D-glucopyranosyloxy-4-hydroxybenzoate, 2-β-D-glucopyranosyloxy-4-hydroxybenzoate Isopropyl acid, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid, 2-β-D-glucopyranosyloxy-5-hydroxybenzoic acid methyl, 2-β-D-glucopyranosyl Ethyl oxy-5-hydroxybenzoate, 2-β-D-glucopyranosyloxy-5-hydroxybenzoate, 2-β-D-glucopyranosyl Carboxymethyl -5-hydroxybenzoic acid isopropyl, and the like.

  This ether compound is obtained by a known method, for example, a direct etherification method between a corresponding alcohol and an alkyl halide, an addition reaction between the corresponding alcohol and an olefin in the presence of a Lewis acid catalyst, a corresponding alcohol and an alkyl halide in the presence of an alkali catalyst. Can be produced by a method of reducing the allyl ether obtained by the addition reaction with, a method of reducing the acetal or ketal produced from the corresponding alcohol and aldehyde or ketone. The blending amount of the ether compound is preferably about 0.01 wt% or more, more preferably about 0.01 wt% or more, more preferably about 0.1 wt% or more in the total amount of the external preparation for skin. The blending amount of the ether compound is preferably about 50% by weight or less, more preferably about 20% by weight or less, and more preferably about 10% by weight or less based on the total amount of the external preparation for skin.

  Examples of hydroxycinnamic acid and derivatives thereof include p-coumaric acid, hydroxycinnamic acid containing p-coumaric acid, and caffeic acid. The amount of hydroxycinnamic acid and its derivative is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The amount of hydroxycinnamic acid and its derivatives is preferably about 5% by weight or less, more preferably about 3% by weight or less, based on the total amount of the external preparation for skin.

  The blending amount of caffeic acid and its derivatives is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The blending amount of caffeic acid and its derivatives is preferably about 5% by weight or less, more preferably about 3% by weight or less, based on the total amount of the external preparation for skin.

  Herbal extracts include mulberry (sakuhakuhi), peony, oxon, chamomile, touki, rosemary, gennoshouko, sicon, tea, kuzukone, clove, licorice, persimmon, orange peel, ginseng, glaze, sanko, barmon winter, Ginger, Matsukasa, Kobaku, Asen Yaku, Huang Gon, Aloe, Altea, Shimotsuke, Dutch Grape, Kina, Comfrey, Roth, Jojoba, Assembly, Western Saw Grass (Achillea millefolium Linn'e (Compositae)) These extracts can be used as well. In the present invention, the herbal medicine and its extract are all herbs, roots, leaves, flowers and seeds of the above herbal medicine, which are dried as necessary to obtain a fine powder, or are immersed and extracted with water and / or an organic solvent. , An extract obtained by filtering the residue, a solution obtained by removing the solvent from the extract, or a fine powder thereof, or dissolving the extract or the solvent-removed product using an appropriate solvent, Dispersed or diluted. The amount of the herbal extract is preferably about 0.0001% by weight or more, more preferably about 0.01% by weight or more, based on the total amount of the external preparation for skin. The blending amount of the crude drug extracts is preferably about 20% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  Natural extracts include yeasts such as Saccharomyces, bacteria, human umbilical cord, yeast, milk-derived protein, silk, wheat, soybeans, cow blood, pig blood, chicken crown, almonds, cacao, macadamia nuts, olives, ginger, corn, bodaige, Pine, mint, burdock, sesame, prune, dokudami, kumaza, camellia, grapefruit, mallow, rice, avocado, cactus, lavender, sunflower, cypress, sesame, lily, yuzu, rose, acerola, cucumber, rice, shea butter, birch , Tomato, garlic, hamamelis, loofah, hop, peach, apricot, lemon, kiwi, dokudami, capsicum, clara, scallop, kohone, sage, sawtooth grass, mallow, senkyu, assembly, thyme, birch, horsetail, loofah, maroonier, Yu Noshita, Arnica, Lily, Artemisia, Acorn, Safflower, Sanshishi, Taiso, Chimpi, Yokuinin, Gardenia, Sawara, Chamomile, Melissa, Biwa, Jatoba and other organic and organic solvents, alcohols, polyhydric alcohols, Examples include natural extracts obtained by extraction or hydrolysis with water, aqueous alcohol or the like. The blending amount of the natural extract is preferably about 0.001% by weight or more, preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  Examples of placenta extracts are extracts obtained by immersing and extracting from the placenta of animals such as humans, monkeys, cows, pigs, sheep, mice, etc. with water and / or organic solvents, and filtering the residue, This extract is obtained by removing the solvent, or a fine powder thereof, or a solution obtained by dissolving, dispersing, or diluting the extract or the solvent-removed product using an appropriate solvent. Specifically, it is marketed as a water-soluble or oil-soluble placenta extract. The amount of placenta extract is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The amount of the placenta extract is preferably about 5% by weight or less, more preferably about 3% by weight or less, based on the total amount of the external preparation for skin.

  Examples of the oil-soluble licorice extract include perennial licorice belonging to the leguminous family (scientific name: Glycyrrhizaglabra linne), lower monohydric alcohols such as methyl alcohol and ethyl alcohol, and liquids such as glycerin, propylene glycol and 1,3-butylene glycol. It is extracted using an extraction solvent such as a polyhydric alcohol. Although the preparation method is not particularly limited, for example, the extraction is performed using various appropriate solvents at a low temperature or from room temperature under heating. As an example of a preferable extraction method, use ethyl alcohol for 2 to 10 hours while heating, then filter, leave the resulting filtrate to stand for another 2 to 3 days, and filter again. The method of performing is mentioned, You may concentrate and dry, after performing heat extraction as needed. The oil-soluble licorice extract thus obtained is a brownish substance having a specific odor and can be used as it is in many cases. It may be used after a purification treatment such as decolorization. As a means for the purification treatment, an activated carbon column or the like may be used, and a normal purification means generally applied to the extracted substance can be arbitrarily selected and used. The amount of blending depends on the quality of the extract used. In a specific case, the amount of the oil-soluble licorice extract is preferably about 0.0001% by weight or more, more preferably about 0.001% by weight or more based on the total amount of the external preparation for skin. In a specific case, the amount of the oil-soluble licorice extract is preferably about 5% by weight or less, more preferably about 3% by weight or less based on the total amount of the external preparation for skin.

  Ceramides and ceramide-like structural substances have effects such as moisturizing, softening, whitening, anti-inflammatory, antioxidant, blood circulation promotion, etc. on the skin. Ceramides are represented by general formula 4, and ceramide-like structural substances are represented by general formula 5 , 6, 7, 8, and 9. Ceramides and ceramide-like structural substances can be used either alone or in combination of two or more. The blending amount of the ceramides and the ceramide-like structural substance is preferably about 0.01% by weight or more, more preferably about 0.05% by weight or more, and more preferably about 0.00% by weight based on the total amount of the external preparation for skin. 1% by weight or more. The blending amount of the ceramides and the ceramide-like structural substance is preferably about 50% by weight or less, more preferably about 20% by weight or less, and more preferably about 10% by weight in the total amount of the external preparation for skin. When it is within the range of this blending amount, it is particularly good in terms of usability, moisturizing effect, rough skin prevention and improvement effect, and stability.

In the general formula 4, R ³ and R ⁴ are the same or different, a hydroxyl group-substituted or unsubstituted C ⁸ to C 26 linear or branched saturated or unsaturated hydrocarbon group. In General Formula 5, R ⁵ is a linear or branched saturated or unsaturated hydrocarbon group having 10 to 26 carbon atoms, and R ⁶ is a linear or branched saturated or unsaturated hydrocarbon group having 9 to 25 carbon atoms. Y and Z are hydrogen atoms or hydroxyl groups, a is 0 or 1, c is an integer of 0 to 4, and b and d are integers of 0 to 3. In General Formula 6, R ⁷ and R ⁸ are the same or different, a linear or branched, saturated or unsaturated, hydroxylated hydrocarbon group having 1 to 40 carbon atoms, and R ⁹ is 1 to 1 carbon atoms. 6 linear or branched alkylene group or a single bond, R ¹⁰ is a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms or a 2,3-dihydroxypropyloxy group, and R ⁹ is a single bond. In this case, R ¹⁰ is a hydrogen atom. In General Formula 7, R ^7a is a hydrocarbon group having 4 to 40 carbon atoms which may be hydroxylated, R ^9a is a linear or branched alkylene group having 3 to 6 carbon atoms, and R ^10b is 1 carbon atom. -12 linear or branched alkoxy groups. In the general formula 8, R ⁷ , R ⁸ , R ^8a and R ^9a are the same as above. In General Formula 9, R ⁷ , R ⁸ and R ⁹ are the same as above, R ^10b is a hydrogen atom, a linear or branched alkoxy group having 1 to 12 carbon atoms, or a 2,3-dihydroxypropyloxy group, When R ⁹ is a single bond, R ^10b is a hydrogen atom.

The ether compound represented by the general formula R ¹¹ —O— (X—O) n—R ¹² has the effect of enhancing the transdermal absorbability of the external preparation for skin of the present invention, and also gives skin irritation. Absent. In this general formula, R ¹¹ and R ¹² may be the same or different and each represents a linear, branched or cyclic alkyl group having 1 to 12, preferably 2 to 22, more preferably 3 to 20 carbon atoms. And at least one of R ¹¹ and R ¹² is preferably branched at 2 or more, particularly at two, specifically, methyl group, butyl n-butyl n-decyl n-dodecyl group n-tetradecyl group n-octadecyl Group, n-eicosyl group, n-tetracosyl group, 1-methylpropyl group, 3-methylhexyl group, 2-methylheptadecyl group, 1,3-dimethylbutyl group, 1,3-dimethylpentyl group, cyclopentyl group, etc. Is mentioned. X is an alkylene group having 1 to 12 carbon atoms, preferably 1 to 8 carbon atoms, and specific examples include a methylene group, an ethylene group, and a butylene group. ^{Incidentally,} the total number of carbon atoms in ^{R 11} and ^{R 12} and X are 10 to 32 is essential, preferably 12 to 28. n is 0 or 1, preferably 0.

  The crude sugar extract is a pigment component exhibiting a brown color, and the dry powder is hygroscopic, has a slight burning odor, and has a slight bitterness. The production method is described in JP-A-60-78912. Specifically, crude sugar (brown sugar) or molasses (by-product generated in the process of producing sugar from brown sugar) is added in an appropriate amount of water. The dye component is adsorbed on the adsorbent after it has been dissolved in the sample and brought into contact with an adsorbent such as a non-polar polystyrene resin adsorbent to adsorb the dye component, and this adsorbent is washed with water to sufficiently remove sugar. Is obtained by elution with a hydrous alcohol having a concentration of 20% or more, followed by concentration, lyophilization, evaporation to dryness, etc., and recrystallization as necessary. The blending amount of the crude sugar extract is preferably about 0.01% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The blending amount of the crude sugar extract is preferably about 10% by weight or less, more preferably about 5% by weight or less, based on the total amount of the external preparation for skin.

  The molasses extract is mainly composed of oligosaccharides, and can be obtained by subjecting molasses to cold or digestion with lower alcohols such as methanol and ethanol, followed by filtration and concentration for decolorization. The blending amount of the molasses extract is preferably about 0.01% by weight or less, more preferably about 0.1% by weight or more based on the total amount of the external preparation for skin. The blending amount of the molasses extract is preferably about 10% by weight or more, more preferably about 5% by weight or more based on the total amount of the external preparation for skin.

  The mycelium culture and its extract are those obtained by culturing mycelium such as mushroom, mushroom, etc. in an appropriate medium, and the culture solution is obtained as it is in the case of liquid culture or obtained in the case of solid culture. This refers to a fine powder obtained by drying the mycelium as necessary. The mycelium culture extract is obtained by immersing and extracting from the above mycelium culture solution, mycelium, or a fine powder thereof with water and / or an organic solvent, and filtering the residue. The extract obtained by removing the solvent from the extract, or a fine powder of these, or the extract or solvent-removed product dissolved, dispersed or diluted by using an appropriate solvent, etc. The blending amount of the mycelium culture and the extract thereof is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The blending amount of the mycelium culture and the extract thereof is preferably about 5% by weight or less, more preferably about 3% by weight or less, based on the total amount of the external preparation for skin.

  The amount of urea is preferably about 0.1% by weight or more, more preferably about 1.0% by weight or more, based on the total amount of the external preparation for skin. The amount of urea is preferably about 20% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  The amount of hinokitiol is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The amount of hinokitiol is preferably about 5% by weight or less, more preferably about 3% by weight or less based on the total amount of the external preparation for skin.

  The amount of sulfur is about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The amount of sulfur is about 5% by weight or less, more preferably about 3% by weight or less, based on the total amount of the external preparation for skin.

  Examples of azelain and derivatives thereof include azelain and azelaic acid. The amount of azelain and derivatives thereof is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The amount of azelain and derivatives thereof is preferably about 5% by weight or less, more preferably about 3% by weight or less, based on the total amount of the external preparation for skin.

  Vitamin E-nicotinate and diisopropylamine dichloroacetate have blood circulation promoting action and cell activation action, promote skin metabolism, and prevent skin aging due to UV damage. The amount of vitamin E-nicotinate is preferably about 0.01% by weight or more, preferably about 5% by weight or less, based on the total amount of the external preparation for skin. The amount of diisopropylamine dichloroacetate is preferably about 0.01% by weight or more, preferably about 5% by weight or less, based on the total amount of the external preparation for skin.

  Deep sea water is seawater obtained at a portion below the sea level of 200 m. Deep sea water has the characteristics of low temperature stability, eutrophication and cleanliness. The blending amount of deep ocean water is preferably about 0.05% by weight or more, more preferably about 0.5% by weight or more, based on the total amount of the external preparation for skin. The blending amount of deep ocean water is preferably about 30% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  Alkaline simple hot spring water refers to hot spring water having a spring temperature of 25 ° C. or higher and a solid component and free carbonic acid content of less than 1,000 mg / kg of water and having a pH of 8.5 or higher and lower than pH 10. The blending amount of the alkaline simple hot spring water is preferably about 0.05% by weight or more, more preferably about 0.5% by weight or more in the total amount of the external preparation for skin. The blending amount of the alkaline simple hot spring water is preferably about 30% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

(7.2.2.2 Whitening ingredients)
As used herein, the term “whitening component” refers to a component that can safely induce a decrease in melanin pigment when used on a skin site with increased melanin pigment.

  Examples of whitening ingredients include: tyrosinase inhibitors, endothelin antagonists, α-MSH inhibitors, α-arbutin, arbutin and its salts and derivatives, ascorbic acid and its derivatives, ellagic acid compounds and their Alkali metal salt, kojic acid and its derivatives, resorcinol derivative, nordihydroguaiaretic acid, teprenone, allantoin, aminoethyl compound, alkylenediaminecarboxylic acid derivative, betaine derivative, acylmethyltaurine, hederacoside, gymnema saponin, beet saponin, γ -Pyrone glycosides, biphenyl compounds, sodium bisulfite, fibronectin, plant extracts and phenols and their derivatives.

  Examples of tyrosinase inhibitors include cell groups or tissue pieces such as roots, hypocotyls, cotyledons, roots of mature bodies, stems, petioles, flowers, pollen of cultured cells of Catharanthus roseus L. (catharanthus roseus L.) ) Is induced in a medium supplemented with plant growth regulators containing plant hormones such as auxin and cytokinin, or Agrobacterium tumefaciens or Agrobacterium rhizogenes is used. A tumor tissue is produced from cultured cells of periwinkle, and callus or tumor tissue is treated with a hydroquinone-α-D-glucose-containing medium (Murashige-Scoom medium, Rinsmeier-Scoom medium, white medium, Gambol). A clear liquid derived from a homogenate of a culture obtained by culturing in a medium, a niche medium, a hella medium, a Schenck-Hildebrand medium, a niche-niche medium, a Korenbach-Schmidt medium, etc. The amount showing the desired anti-tyrosinase activity may be used.

  Endothelin antagonists include BE-18257s (JP-A-3-94692), WS7338s (JP-A-3-130299), anthraquinone derivatives (JP-A-3-47163), TAN-1415s (special (Kaihei 4-134048). The blending amount of the endothelin antagonist is preferably about 0.001% by weight, more preferably about 0.05% by weight or more based on the total amount of the external preparation for skin. The blending amount of the endothelin antagonist is preferably about 10% by weight or less, more preferably about 5% by weight or less, based on the total amount of the external preparation for skin.

  The α-MSH inhibitor means a group of substances that inhibit the production of α-melanotropin that is deeply involved in melanin production. The blending amount of the α-MSH inhibitor is preferably about 0.001% by weight or more, more preferably about 0.05% by weight or more, based on the total amount of the external preparation for skin. The blending amount of the α-MSH inhibitor is preferably about 30% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  Examples of α-arbutin, arbutin and salts and derivatives thereof include α-arbutin, arbutin, α-arbutin-α-glucoside, α-arbutin-α-maltoside. The blending amount of α-arbutin, arbutin, a salt thereof and a derivative thereof is preferably about 0.001% by weight or more, more preferably about 0.05% by weight or more, based on the total amount of the external preparation for skin. The blending amount of α-arbutin, arbutin, a salt thereof and a derivative thereof is preferably about 10% by weight or less, more preferably about 3% by weight or less based on the total amount of the external preparation for skin.

  Examples of ascorbic acid and its derivatives used as a whitening component include ascorbic acid monostearate, ascorbic acid monopalmitate, ascorbic acid monoalkyl esters such as ascorbic acid monooleate, ascorbic acid monophosphate, ascorbic acid-2- Ascorbic acid monoester derivatives such as sulfuric acid, ascorbic acid distearate, ascorbic acid dipalmitate, ascorbic acid dioleate, ascorbic acid diester derivatives such as ascorbic acid diphosphate, ascorbic acid tristearate, ascorbic acid tripalmitate, ascorbic acid trio Ascorbic acid trialkyl esters such as ascorbic acid, ascorbic acid triester derivatives such as ascorbic acid triphosphate, Such as ascorbic acid glycosides such as Colvin acid-2-glucoside and the like. In particular, L-ascorbic acid is generally referred to as vitamin C, and has a cell respiration action, an enzyme activation action, a collagen formation action due to its strong reduction action, and a melanin reduction action. The amount of ascorbic acid and its derivative is preferably about 0.01% by weight or more based on the total amount of the external preparation for skin. There is no particular upper limit to the amount of ascorbic acid and its derivatives, but it is preferably about 10% by weight or less.

  The ellagic acid compound and its alkali metal salt are for improving the long-term storage stability of the external preparation for skin of the present invention, and are represented by the general formula 10. Examples of alkali metal salts of ellagic acid compounds include Na salts and K salts. The blending amount of the ellagic acid compound and its alkali metal salt is preferably about 0.001% by weight or more, more preferably about 0.05% by weight or more, based on the total amount of the external preparation for skin. The blending amount of the ellagic acid compound and its alkali metal salt is preferably about 30% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

In General Formula 10, R ¹³ , R ¹⁴ , R ¹⁵ , and R ¹⁶ are a hydrogen atom, an alkyl group having 1 to 20 carbon atoms (for example, a methyl group, an ethyl group, a propyl group, etc.), and an acyl group having 1 to 20 carbon atoms. (e.g. acetyl group, propionyl group, _{etc.), - (C m H 2m} -O) n H (m is 2 or 3, n is an integer of 1 or more, particularly 5 to 40 is preferred) polyoxyalkylene group represented by ( For example, polyoxyethylene group, polyoxypropylene group) and sugar residues represented by the general formula 11, which may be the same or different from each other. R ¹⁷ is a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 8 carbon atoms.

Ellagic acid compounds and alkali metal salts thereof are ellagic acid, 3,4-di-o-methylellagic acid, 3,3′-di-o-methylellagic acid, 3,3 ′, 4-tri-o-methylellag Acids, 3,3 ′, 4,4′-tetra-o-methyl-5-methoxyellagic acid, 3-o-ethyl-4-o-methyl-5-hydroxyellagic acid, amritoside, and these Examples include alkali metal salts. These ellagic acid compounds include strawberry, cod (Caesalupinia Spinosa), eucalyptus (Eucalyptus), apple, poisonous eel (Koreaia japonica), radiata pine, bearberry, pomegranate, anmaroc, cucumber, enfuyo, geijicha, coconut, , Kenjin, Kunaka, Sangkyukon, Sangyoukou, Syufubou, Senkutsusai, Shirogensokan, Daihyosou, Doumouanyou, Haouben, Bansekiryukan, Bansekiryuhi, Boka, Moshoshishi, Yuzukanyu, Syukan Heavens such as kon, bansekiryuyo, kyukubokubibi, sidkon, chinsou, gennoshouko It can be obtained from the natural thing.

  Kojic acid and its derivatives include kojic acid, kojic acid glycoside, kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, kojic acid monostearate, kojic acid monocinnamoate, kojic acid monobenzoate, etc. And monoesters such as kojic acid dibutyrate, kojic acid dipalmitate, kojic acid distearate, kojic acid dioleate, and the like. The amount of kojic acid and its derivative is preferably about 0.001% by weight or more, more preferably about 0.05% by weight or more, further preferably about 0.01% by weight in the total amount of the external preparation for skin. That's it. The amount of kojic acid and its derivative is preferably about 30% by weight or less, more preferably about 10% by weight or less, and still more preferably about 5% by weight or less based on the total amount of the external preparation for skin.

  The resorcinol derivative has a blood circulation promoting action and a cell activation action, prevents drying of the epidermis, promotes skin metabolism, and prevents skin aging due to UV damage. Specific examples include 4-n-ethylresorcinol, 4-n-butylresorcinol, 4-n-hexylresorcinol, 4-isoamylresorcinol and the like. The amount of the resorcinol derivative is preferably about 0.0001% by weight or more, more preferably about 0.01% by weight or more, based on the total amount of the external preparation for skin. The amount of the resorcinol derivative is preferably about 20% by weight or less, preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  Nordihydroguaiaretic acid is a substance generally known as an antioxidant or a lipoxygenase inhibitor, and is applied to cosmetics, medical products and the like for the purpose of antioxidant and drug stabilization. The blending amount of nordihydroguaiaretic acid is preferably about 0.01% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The blending amount of nordihydroguaiaretic acid is preferably about 10% by weight or less, more preferably about 5% by weight or less, based on the total amount of the external preparation for skin.

  The chemical name of teprenone is geranylgeranylacetone, which has a mucosal protective and repairing action, a cell growth activating action, a phospholipid synthesis promoting action and the like. The amount of teprenone is preferably about 0.01% by weight or more, more preferably about 0.5% by weight or more, and further preferably about 1.0% by weight or more based on the total amount of the external preparation for skin. The amount of teprenone is preferably about 20% by weight or less, more preferably about 10% by weight or less, still more preferably about 10% by weight or less based on the total amount of the external preparation for skin.

  Allantoin is used as a therapeutic agent for various diseases in dermatology, and effectively acts for skin wound treatment and prevention of rough skin. Examples of allantoin derivatives include dihydroxyaluminum allantoinate and chlorohydroxyaluminum allantoinate. The amount of allantoin and allantoin derivative is preferably about 0.01 or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The amount of allantoin and allantoin derivative is preferably about 5% by weight or less, more preferably about 3% by weight or less, based on the total amount of the external preparation for skin.

The aminoethyl compound is used for preventing and improving rough skin and improving dullness, and is represented by NH ₂ CH ₂ CH ₂ X (X is —SO ₂ H or —SO ₂ SH). The compounding amount of the aminoethyl compound is preferably about 0.0001% by weight or more, more preferably about 0.001% by weight or more, based on the total amount of the external preparation for skin. The compounding amount of the aminoethyl compound is preferably about 1.0% by weight or less, more preferably about 0.3% by weight or less, based on the total amount of the external preparation for skin.

  Alkylene diamine carboxylic acid derivatives are used to enhance the storage stability of external preparations for skin, in particular ethylene diamine tetraacetic acid and alkali metal salts such as Na, K and Li salts thereof, alkaline earth metal salts such as Ca and Mg, Ammonium salts, alkanol salts and the like are preferable, and Na salts are more preferable. The blending amount of the alkylene diamine carboxylic acid derivative is preferably about 0.01% by weight or more, more preferably about 0.05% by weight or more, based on the total amount of the external preparation for skin. The blending amount of the alkylenediaminecarboxylic acid derivative is preferably about 0.5% by weight or less, preferably about 0.5% by weight or less, based on the total amount of the external preparation for skin.

  The betaine derivative is used as a transdermal enhancer and is an alkyldimethylamino acid represented by general formula 12, 2-alkyl-1-carboxymethyl-1-hydroxyethyl-2-imidazoline represented by general formula 13, and general formula 14 N- (3-acylaminopropyl) -N, N-dimethylaminoacetic acid represented by the formula: N-alkyl-N, N-dimethyl-3-amino-2-hydroxypropanesulfonic acid represented by the general formula 15: preferable.

  Acylmethyl taurine is used as a transdermal enhancer and is represented by general formula 16.

The total amount of the betaine derivative and the acylmethyl taurine is preferably about 0.01% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The total amount of the betaine derivative and the acylmethyl taurine is preferably about 30% by weight or less, preferably about 20% by weight or less, based on the total amount of the external preparation for skin.

  Hederacoside is a triterpenoid saponin obtained from an extract of muclodine (Enpine: Sapindus mukurossi Gaertn.) Or akebi (Akebia quinata Decne.). There are salts, ammonium salts, basic amino acid salts, alkanolamine salts, esters and the like, and these may be used as they are in the extract. The blending amount of hederacoside and a salt thereof is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The blending amount of hederacoside and a salt thereof is preferably about 20% by weight or less, more preferably about 5% by weight or less based on the total amount of the external preparation for skin.

  Gymnemasaponin is a triterpenoid saponin obtained from an extract of Gymnemy drum or Gymnema sylvestre R. Br. Native to India. Examples of the salt include alkali salts such as Na salt and K salt. There are metal salts, ammonium salts, basic amino acid salts, alkanolamine salts, esters and the like, and these may be used as they are in the extract. The amount of Gymnemasaponin is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The amount of Gymnemasaponin is preferably about 20% by weight or less, more preferably about 5% by weight or less, based on the total amount of the external preparation for skin.

  Beet saponin is an oleanolic acid glycoside obtained from an extract of a red crustacean sugar beet, and as its salt, alkali metal salt such as Na salt and K salt, ammonium salt, basic amino acid salt, alkanolamine salt, ester These may be used as an extract. The amount of beet saponin is preferably about 0.001% by weight or more, more preferably about 0.1% by weight or more, based on the total amount of the external preparation for skin. The amount of beet saponin is preferably about 20% by weight or less, more preferably about 5% by weight or less, based on the total amount of the external preparation for skin.

  γ-pyrone glycoside has an action of preventing spots and buckwheat caused by sunburn, and is represented by general formula 17 maltol-3-O- (6′-O-apiosyl) -glucoside or maltol-3-O. -It is a glucoside, for example, what was extract | collected from the Kakkon extract by column chromatography, preparative HPLC, a thin layer chromatography etc. can be used. The blending amount of γ-pyrone glycoside is preferably about 0.00001% by weight or more, more preferably about 0.0001% by weight or more based on the total amount of the external preparation for skin. The blending amount of γ-pyrone glycoside is preferably about 2.5% by weight or less, more preferably about 1% by weight or less, based on the total amount of the external preparation for skin.

The biphenyl compound has a tyrosinase activity inhibitory effect and a melanin production inhibitory effect, and is represented by general formulas 18 and 19. Specific examples include dehydrodichloroeosol, dehydrodioigenol, and tetrahydromagnolol. The amount of the biphenyl compound is preferably about 0.0001% by weight or more, more preferably about 0.001% by weight or more, based on the total amount of the external preparation for skin. The blending amount of the biphenyl compound is preferably about 20% by weight or less, more preferably about 5% by weight or less, based on the total amount of the external preparation for skin.

In the general formula 18.19, R ²⁴ is CH ₃ , C ₂ H ₅ , C ₃ H ₇ , CH ₂ OH, C ₃ H ₆ OH, CH ₂ CH═CH ₂ , R ²⁵ is a hydrogen atom, carbon It is a linear or branched saturated hydrocarbon group having a number of 1 to 8.

  Sodium bisulfite is known as a substance that exhibits an effect on stabilizing arbutin in a skin external preparation (Japanese Patent No. 2107858), but hydroquinone-α-D-glucose also exhibits the same effect. The blending amount is such that hydroquinone-α-D-glucose: sodium hydrogen sulfite is 1: 0.0001 to 1, preferably 1: 0.001 to 0.1 by weight.

  Fibronectin (cold insoluble globulin) has the effect of improving the whitening effect of hydroquinone-α-D-glucose in the present invention. The amount of fibronectin is preferably about 0.000001% by weight or more, preferably about 0.1% by weight or less, based on the total amount of the external preparation for skin.

  Plant extracts as whitening agents include asparagus extract, artea extract, ibukitorano extract, ginseng extract, pea extract, ages extract, ogon extract, onionis extract, seaweed extract, fire Thorn extract, licorice extract, raspberry extract, cucumber extract, brown sugar extract, keiket extract, gokahi extract, wheat germ extract, saicin extract, hawthorn extract, sunpens extract, peony extract, Silica lily extract, Sempukuka extract, Sakuhakuhi extract, Soybean extract, Placenta extract, Taran extract, Tea extract, Toki extract, Molasses extract, Neubara extract, Juniper extract, Grape seed extract, Beech tree Extract, Flow demanita extract, Hop extract, Mikaika extract, Mokka extract, Yukinoshita extract, Yokui Down extract, etc. may be mentioned. Swingle extract is formulated by selecting the one or more appropriate. The blending amount of the whitening agent component is preferably about 0.01% by weight or more, preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

  Phenol and its derivatives as whitening agents include hydroquinone glycoside, hydroquinone monoethyl ether, hydroquinone mono n-propyl ether, hydroquinone mono n-butyl ether, hydroquinone mono n-hexadecyl ether, hydroquinone mono n-octadecyl ether, p -Ethylphenol, pn-propylphenol, pn-butylphenol, pt-butylphenol, p-isopropylphenol, p-hexadecylphenol, p-octadecylphenol, 4-isopropylcatechol monobutyl ester, 4-isopropyl And catechol monoheptadecaester. The blending amount of phenol and its derivative is preferably about 0.01% by weight or more, more preferably about 0.1% by weight, based on the total amount of the external preparation for skin. The blending amount of phenol and its derivative is preferably about 20% by weight or less, more preferably about 10% by weight or less, based on the total amount of the external preparation for skin.

(7.2.2.3 UV absorber)
In this specification, the term “ultraviolet absorber” is also referred to as an organic ultraviolet absorber, and refers to a compound that absorbs ultraviolet rays, converts them into infrared rays, visible rays, etc. that have little influence on the human body and emits them.

  As the ultraviolet absorber, any ultraviolet absorber that is widely used in conventional external preparations for skin can be used. The blending amount of the ultraviolet absorber is preferably about 0.01% by weight or more, more preferably 0.5% by weight or more, based on the total amount of the external preparation for skin. The blending amount of the ultraviolet absorber is preferably about 10% by weight or less, preferably about 8% by weight or less, based on the total amount of the external preparation for skin.

  Examples of UV absorbers include: benzoic acid UV absorbers, anthranilic acid UV absorbers, salicylic acid UV absorbers, cinnamic acid UV absorbers, benzophenone UV absorbers, and other UV absorbers. Selected from the group consisting of absorbents.

  Examples of the benzoic acid-based ultraviolet absorber include paraaminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin ester, N, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester, N, N-dimethyl. Examples include PABA ethyl ester, N, N-dimethyl PABA butyl ester, N, N-dimethyl PABA amyl ester, and N, N-dimethyl PABA octyl ester.

  An example of an anthranilic acid ultraviolet absorber is homomenthyl-N-acetylanthranilate.

  Examples of salicylic acid-based UV absorbers include amyl salicylate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, and p-isopropanol phenyl salicylate.

  Examples of cinnamic acid UV absorbers include octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4-diisopropyl. Cinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, octyl-p-methoxycinnamate (2-ethylhexyl-p-methoxycinnamate), 2-ethoxyethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α -Cyano- - phenyl cinnamate, glyceryl mono-2-ethyl hexanoyl - di p-methoxycinnamate and the like.

  Examples of benzophenone ultraviolet absorbers include 2,4-dihydroxybenzophenone, 2,2′-dihydroxy-4-methoxybenzophenone, 2,2′-dihydroxy-4,4′-dimethoxybenzophenone, 2,2 ′, 4. , 4′-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy4′-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, Examples include 2-ethylhexyl-4′-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, and 4-hydroxy-3-carboxybenzophenone.

  Examples of other ultraviolet absorbers include 3- (4′-methylbenzylidene) -d, l-camphor, 3-benzylidene-d, l-camphor, urocanic acid, urocanic acid ethyl ester, 2-phenyl-5 Methylbenzoxazole, 2,2′-hydroxy-5-methylphenylbenzotriazole, 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole, 2- (2′-hydroxy-5′-methyl) Phenyl) benzotriazole, dibenzalazine, dianisoylmethane, 4-methoxy-4'-tert-butyldibenzoylmethane, and 5- (3,3-dimethyl-2-norbornylidene) -3-pentan-2-one .

(7.2.2.4 Anti-inflammatory agent)
As used herein, the term “anti-inflammatory agent” refers to a compound that has the property of suppressing an inflammatory process in a specific local area.

  The compounding amount of the anti-inflammatory agent varies depending on the type of the anti-inflammatory agent and is not uniformly determined, but is preferably about 0.01% by weight or more, preferably about 1% by weight or less, based on the total amount of the external preparation for skin. is there.

  Examples of anti-inflammatory agents include: zinc oxide, sulfur and its derivatives, glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate and their derivatives, and salts thereof, β-glycyrrhetinic acid, glycyrrhetin Glycyrrhetinic acid and its derivatives such as stearyl acid, disodium 3-succinyloxyglycyrrhetinate and their salts, tranexamic acid, chondroitin sulfate, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene and their derivatives and Their salts and extracts of various microorganisms and animals and plants.

(7.2.2.5 Cell Activator)
In this specification, the term “cell activator” refers to a substance having an action of promoting cell proliferation. The compounding amount of the cell activator varies depending on the type of the cell activator, but is usually 0.01 to 5% by weight with respect to the external preparation for skin.

  Examples of cell activators include: CoQ10 deoxyribonucleic acid and salts thereof, adenylate derivatives such as adenosine triphosphate and adenosine monophosphate and salts thereof, ribonucleic acid and salts thereof, cyclic AMP, Retinals such as cyclic GMP, flavin adenine nucleotides, guanine, adenine, cytosine, thymine, xanthine and their derivatives, caffeine, theopherin and its salts, retinol and retinol palmitate, retinol acetate, retinal such as retinal and dehydroretinal Derivatives, carotenoids such as carotenes and vitamins A, thiamine and thiamine hydrochloride, thiamine salts such as thiamine sulfate, riboflavin salts such as riboflavin and riboflavin acetate, pyridoxine and salts Pyridoxine salts such as pyridoxine, pyridoxine dioctanoate, flavin adenine nucleotides, cyanocobalamin, folic acid, nicotinic acid and nicotinamide, nicotinic acid derivatives such as benzyl nicotinate, vitamin B such as choline, γ-linolenic acid and Derivatives thereof, eicosapentaenoic acid and derivatives thereof, estradiol and derivatives thereof and salts thereof, organic acids such as glycolic acid, succinic acid, lactic acid and salicylic acid and derivatives thereof and salts thereof.

(7.2.2.6 Antioxidant)
In this specification, the term “antioxidant” refers to a component added to suppress oxidation of components in a product.

  The content of the antioxidant varies depending on the kind of components of the antioxidant and is not uniformly determined, but is preferably about 0.01% by weight or more, preferably about 10% by weight based on the total amount of the external preparation for skin. It is as follows. When a plant extract or the like is used as an extract, the amount is in terms of dry solid content.

  Examples of antioxidants include: Retinol, dehydroretinol, retinol acetate, retinol palmitate, retinal, retinoic acid, vitamin A oils such as vitamin A oil and their derivatives and their salts, α-carotene , Β-carotene, γ-carotene, cryptoxanthine, astaxanthin, fucoxanthin and other carotenoids and derivatives thereof, pyridoxine, pyridoxal, pyridoxal-5-phosphate ester, vitamin Bs such as pyridoxamine, derivatives thereof and salts thereof Vitamin Cs such as ascorbic acid, sodium ascorbate, ascorbyl stearate, ascorbyl palmitate, ascorbyl dipalmitate, magnesium ascorbate, derivatives thereof and salts thereof, Vitamin Ds such as lugocalciferol, cholecalciferol, 1,2,5-dihydroxy-cholecalciferol, derivatives and salts thereof, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α Vitamin E such as tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, tocopherol acetate, tocopherol nicotinate, their derivatives and their salts, Trolox, its derivatives and their salts, dihydroxytoluene, butylhydroxy Eryso such as toluene, butylhydroxyanisole, dibutylhydroxytoluene, α-lipoic acid, dehydrolipoic acid, glutathione, its derivatives and their salts, uric acid, erythorbic acid, sodium erythorbate Binic acid, its derivatives and their salts, gallic acid such as gallic acid, propyl gallate, its derivatives and their salts, rutin such as rutin, α-glycosyl-rutin, its derivatives and their salts, tryptophan, its derivatives And their salts, histidine, its derivatives and their salts, cysteine derivatives such as N-acetylcysteine, N-acetylhomocysteine, N-octanoylcysteine, N-acetylcysteine methyl ester and their salts, N, N ′ Cystine derivatives such as diacetylcystine dimethyl ester, N, N′-dioctanoyl cystine dimethyl ester, N, N′-dioctanoyl homocystine dimethyl ester and salts thereof, carnosine and derivatives thereof and salts thereof, homocarnosine and Their derivatives and their Salts, anserine and derivatives thereof and salts thereof, calcinin and derivatives thereof and salts thereof, dipeptide or tripeptide derivatives containing histidine and / or tryptophan and / or histamine and salts thereof, flavanones, flavones, anthocyanins, anthocyanidins, flavonols Flavonoids such as quercetin, quercitrin, myricetin, fisetin, hamelitannin, catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, tannic acid, caffeic acid, ferulic acid, protocatechuic acid, chalcone , Oryzanol, carnosol, sesamol, sesamin, sesamorin, zingerone, curcumin, tetrahydrocurcumin, clobamide, deoxyclobamide, show All, capsaicin, vanillylamide, ellagic acid, bromophenol, flavoglasin, melanoidin, riboflavin, riboflavin butyrate, flavin mononucleotide, flavin adenine nucleotide, ubiquinone, ubiquinol, mannitol, bilirubin, cholesterol, ebselen, selenomethionine, ceruloplasmin, transferrin , Lactoferrin, albumin, bilirubin, superoxide dismutase, catalase, glutathione peroxidase, metallothionein, O-phosphono-pyridoxylidene rhodamine, and N- (2-hydroxybenzyl) amino acid described in US Pat. No. 5,594,012, Derivatives and their salts, and N- (4-pyridoxymethylene) amino acids, their derivatives and And their salts.

  Examples of ascorbic acid and its derivatives and salts used as antioxidants include ascorbic acid monostearate, ascorbic acid monopalmitate, ascorbic acid monoalkyl esters such as ascorbic acid monooleate, ascorbic acid monophosphate, ascorbic acid 2-ascorbic acid monoester derivatives such as sulfuric acid, ascorbic acid distearate, ascorbic acid dipalmitate, ascorbic acid dioleate, ascorbic acid diester derivatives such as ascorbic acid diphosphate, ascorbic acid tristearate, ascorbic acid tripalmitate, Ascorbic acid trialkyl esters such as ascorbic acid trioleate and ascorbic acid tries such as ascorbic acid triphosphate Le derivatives, ascorbic acid glycosides and the like, such as ascorbic acid-2-glucoside. In particular, L-ascorbic acid is generally referred to as vitamin C, and has a cell respiration action, an enzyme activation action, a collagen formation action due to its strong reduction action, and a melanin reduction action. The blending amount is effective when blended in an amount of 0.01% by weight or more in the total amount of the external preparation for skin, and the upper limit is about 10% by weight.

(7.2.3. Other components)
In addition to the above-described components, the external preparation for skin of the present invention is usually used for other external preparations for skin, such as cosmetics and pharmaceuticals, for example, an additive component that is usually added to the external preparation for skin, for example, lower alcohol. , Silicones, fats and oils, ester oils, sterols and their derivatives, hydrocarbons and other oily components, oils, antioxidants, surfactants, moisturizers, wetting materials, perfumes, water, colorants, powders, Drugs, chelating agents, pH adjusters, emulsifiers, solubilizers, thickeners, gelling agents, preservatives, bactericides, acids and alkalis, UV absorbers, anti-inflammatory agents, whitening agents, solvents, exfoliating and dissolving Agent, anti-inflammatory agent, refreshing agent, astringent, polymer powder, hydroxy acid, vitamins and their derivatives, saccharides and their derivatives, organic acids, enzymes, inorganic powders, etc., as needed You can do this Et Quantitatively not to impair the effects of the present invention, it must be used in the qualitative range.

  Thus, the hesperetin dispersion liquid or hesperetin powder of the present invention is incorporated into cosmetics such as emulsions, lotions, creams, cosmetics, foundations, masks, shampoos, facial cleansers, etc. Thereby, the skin external preparation which raises a moisturizing effect and a collagen production promotion effect is implement | achieved. In addition, it is more effective when the hesperetin dispersion or hesperetin powder of the present invention is used in combination with other moisturizing ingredients and collagen production promoting effects. Other moisturizing ingredients or collagen production promoting effects include, for example, magnesium ascorbate phosphate, sodium ascorbate phosphate, sulfate ascorbate, glucoside ascorbate, sodium ascorbate, ascorbate monostearate, palmitate ascorbate, ascorbate Disodium acid sulfate, calcium ascorbate, glycerin, propylene glycol, 1,3-butylene glycol, sodium dl-pyrrolidonecarboxylate, sodium lactate, sorbitol, sodium hyaluronate, hyaluronic acid, urea, collagen, marine collagen, glucose, Jojoba oil, amino acid, isoflavone, ceramide, chamomile extract, sericin, polyethylene glycol, dimethyl ether Tell, Silk Sericin, Shikon Extract, Toki Extract, Olive Oil, Trehalose, Aloe Extract, Seaweed Extract, Rosemary Oil, Chamomile Extract, Lactic Acid, Red Algae Extract, Avocado Extract, Loofah Water, Ogon Extract, Shikon Extract, Sakuhaku Extract, Netherlands Mustard extract, Soybean extract, Sage extract, Glycine, Cysteine, Herbal extract, Squalane, Royal jelly extract, Lactic acid bacteria fermented extract, Rice extract, Wanhan plant extract, etc. When one or more other moisturizing components and collagen production promoting effects are used in combination with the hesperetin dispersion or hesperetin powder of the present invention, there is a synergistic effect that enhances the effects of each other.

  That is, the present invention relates to ascorbic acid and derivatives thereof, vitamins other than ascorbic acid, sugars and sugar derivatives, amino acids and derivatives thereof, polyhydric alcohols, phenols and derivatives thereof, collagens, hydroxycarboxylic acids and salts thereof, hydroxysalicylic acid Glycoside, hydroxysalicylic acid aliphatic ester glycoside, hydroxycinnamic acid and its derivatives, caffeic acid and its derivatives, herbal extracts, natural extracts, placenta extract, oil-soluble licorice extract, ceramides, Ceramide-like structure, crude sugar extract, molasses extract, mycelium culture and its extract, urea, hinokitiol, sulfur, azelain, deep water, alkaline simple hot spring water, UV absorber, cell activator, antioxidant And other moisturizers, tyrosinase inhibitors, endothelin antagonists, α- SH inhibitor, α-arbutin, arbutin and salts thereof, as well as derivatives thereof, ascorbic acid and derivatives thereof, ellagic acid compounds and alkali metal salts thereof, kojic acid and derivatives thereof, resorcinol derivatives, nordihydroguaiaretic acid, teprenone , Allantoin, aminoethyl compound, alkylenediamine carboxylic acid derivative, betaine derivative, acylmethyl taurine, hederacoside, gymnema saponin, beet saponin, γ-pyrone glycoside, biphenyl compound, sodium bisulfite, fibronectin, plant extracts and the like The gist is a skin external preparation characterized by containing at least one component selected from components used for a whitening agent other than the above and the hesperetin dispersion or hesperetin powder of the present invention.

  The content of hesperetin particles in the external preparation for skin of the present invention is preferably 0.01% by weight or more, more preferably about 0.05% by weight or more, and further preferably about 0.1% by weight or more. More preferably about 0.3% by weight or more, still more preferably about 0.5% by weight or more. The content of the hesperetin particles in the external preparation for skin of the present invention is, for example, about 1% by weight or more, about 3% by weight or more, about 5% by weight or more, about 10% by weight or more, about 15% by weight or more, about 20% by weight. % Or more, about 25% or more, about 30% or more, about 35% or more, about 40% or more, about 45% or more, and the like.

  There is no particular upper limit to the content of hesperetin particles in the external preparation for skin of the present invention. The content of the hesperetin particles in the external preparation for skin of the present invention is, for example, about 90% by weight or less, about 85% by weight or less, about 80% by weight or less, about 70% by weight or less, about 60% by weight or less, about 50% by weight. % Or less, about 45% or less, about 40% or less, about 35% or less, about 30% or less, about 20% or less, about 10% or less.

  The application amount of hesperetin per day of the external preparation for skin of the present invention is preferably about 2 μg or more, more preferably about 3 μg or more, further preferably about 5 μg (body weight) or more, and most preferably about 10 μg or more. It is. The amount of hesperetin applied per day is preferably about 200 mg or less, more preferably about 150 mg or less, still more preferably about 100 mg or less, and most preferably about 50 mg or less. In certain embodiments, for example, it may be 40 mg or less, 30 mg or less, 20 mg or less, 10 mg or less, or 5 mg or less.

(7.3 Textile or clothing)
The hesperetin dispersion and powder of the present invention can also be produced from the fiber or fabric by mixing the hesperetin dispersion and powder of the present invention into a fiber material, impregnating the fiber, or applying to the surface of the fabric. It can also be used for the production of garments containing hesperetin in such a way that hesperetin is transdermally absorbed when the produced garment (for example, underwear, etc.) comes into contact with the skin.

  The content of hesperetin particles in the fiber or garment of the present invention is preferably about 0.01% by weight or more, more preferably about 0.05% by weight or more, and further preferably about 0.1% by weight or more. More preferably, it is about 0.3% by weight or more, and more preferably about 0.5% by weight or more. The content of hesperetin particles in the fiber or garment of the present invention is, for example, about 1% by weight or more, about 3% by weight or more, about 5% by weight or more, about 10% by weight or more, about 15% by weight or more, about 20% by weight. % Or more, about 25% or more, about 30% or more, about 35% or more, about 40% or more, about 45% or more, and the like.

  There is no particular upper limit to the content of hesperetin particles in the fiber or clothing of the present invention. The content of hesperetin particles in the fiber or clothing of the present invention is, for example, about 90% by weight or less, about 85% by weight or less, about 80% by weight or less, about 70% by weight or less, about 60% by weight or less, about 50% by weight. % Or less, about 45% or less, about 40% or less, about 35% or less, about 30% or less, about 20% or less, about 10% or less.

  Those containing the hesperetin dispersion or powder of the present invention exhibit significantly superior efficacy when used in the body than those containing conventional hesperetin.

(8. Method for confirming absorbability of hesperetin dispersion or hesperetin powder of the present invention)
The hesperetin dispersions and powders of the present invention are stable hesperetin dispersions or can form such dispersions, so that when ingested in the body, such as mere hesperetin powder, unstable conventional hesperetin dispersions, etc. In comparison, the absorbability is remarkably improved.

  The absorbability of the hesperetin dispersion or hesperetin powder of the present invention can be confirmed using methods known in the art. The absorbability of the hesperetin dispersion or hesperetin powder of the present invention can be measured, for example, as follows. Animals (eg, 7-week-old male ddY mice) preliminarily raised (eg, about 3 days to 1 week) are fasted (eg, about 14 hours) and orally administered with a predetermined concentration of hesperetin dispersion (eg, 200 μl). To do. It may be administered directly to the stomach using a sonde. After administration, blood is collected over time (eg, from the heart) and serum is separated. Next, a solution containing sulfatase and glucuronidase is added to the serum for reaction, then acetonitrile is added for centrifugation, and the supernatant is dried by concentration centrifugation. This was dissolved in acetonitrile / methanol / water (50:20:30, v / v / v), stirred, sonicated, subjected to high performance liquid chromatography (HPLC) and detected with an electrochemical detector, The amount of hesperetin derivative in the obtained serum is quantified.

Alternatively, the resulting blood is A. Boutin et al. (The American)
After pretreatment by society for Pharmacology and Experimental Therapeutics, 21, 1157-1166 (1993), the amount of hesperetin contained therein may be quantified using HPLC. J. et al. A. The method of Boutin et al. Is as follows. Add 1000 μl of acetonitrile to 500 μl of collected blood, shake well, and let stand for 15 minutes. After centrifugation at 5500 rpm for 20 minutes, the supernatant is taken and lyophilized. Lyophilized samples are dissolved in 100 μl of acetonitrile / distilled water (20/80; V / V, 0.01 M NaOH) solution and analyzed by HPLC. The basic HPLC conditions are as follows: column: ODS, column temperature: 40 ° C., eluent: acetonitrile / distilled water (20/80; V / V), flow rate: 0.5 ml / min, detection: UV 280 nm. The concentration of hesperetin in the blood is determined by preparing a calibration curve using hesperetin of known concentration. In addition to mice, rats can also be used as experimental animals.

  EXAMPLES The present invention will be specifically described below with reference to examples, but is not limited thereto.

Example 1 Production of Hesperetin Dispersion
Reduced starch saccharified product (manufactured by Towa Kasei Kogyo Co., Ltd .; trade name Amamiru; solid content 70%) 715.5 g, surfactant decaglycerin monooleate (manufactured by Taiyo Kagaku Co., Ltd .; trade name Sunsoft Q-) 17Y; Decaglycerin monooleate; hydroxyl value 868; primary hydroxyl group ratio 59.6% 10 g, glyceryl monostearate (manufactured by Taiyo Kagaku Co., Ltd .; trade name Sunsoft No. 621B; monostearic acid citrate Glycerin (10 g) and enzyme-degraded lecithin (manufactured by Taiyo Kagaku Co., Ltd .; trade name sun lecithin A-1; content of enzyme-decomposed lecithin 33.3%; decomposed by phospholipase A ₂ ; decomposition rate of 50% or more) were added, Heat to 80 ° C. and mix well. Hesperetin (manufactured by Ezaki Glico Co., Ltd .; powder with an average particle size of about 20 μm; purity 90%) and alginic acid ester (manufactured by Kimika Co., Ltd .; trade name Kimiloid NLS-K; alginate esterified with propylene glycol) ; Esterification degree 80%) 10 g of powder mixed sufficiently in advance was added, and 79.5 g of water was further added and stirred uniformly at 80 ° C. This was put into a dyno mill (Shinmaru Enterprises Co., Ltd.), which is a continuous wet grinder, and continuously pulverized for 30 minutes to obtain 710 g of the hesperetin dispersion of the present invention. The dyno mill had a pulverization chamber capacity of 0.6 liter, and 0.48 L of zirconia beads having a diameter of 0.8 mm was used as the pulverization medium.

  The dispersion was appropriately diluted with water at the time of measurement, and the particle size was measured with a wet particle size distribution meter manufactured by Beckman Coulter. The average particle size of the particles in the dispersion was 0.7 μm.

( Example 1A ; production of hesperetin dispersion)
Reduced starch saccharified product (manufactured by Towa Kasei Kogyo Co., Ltd .; trade name: Amami; solid content: 70%), 715.5 g; Content 33.3%; decomposed by phospholipase A ₂ ; decomposition rate of 50% or more) was added, and heated to 80 ° C. and mixed well. Hesperetin (manufactured by Ezaki Glico Co., Ltd .; powder with an average particle size of about 20 μm; purity 90%) and alginic acid ester (manufactured by Kimika Co., Ltd .; trade name Kimiloid NLS-K; alginate esterified with propylene glycol) ; Esterification degree 80%) 10 g of powder mixed sufficiently in advance was added, and 99.5 g of water was further added and stirred uniformly at 80 ° C. This was put into a dyno mill (Shinmaru Enterprises Co., Ltd.), which is a continuous wet grinder, and continuously pulverized for 30 minutes to obtain 710 g of a hesperetin dispersion. The dyno mill had a pulverization chamber capacity of 0.6 liter, and 0.48 L of zirconia beads having a diameter of 0.8 mm was used as the pulverization medium.

  The dispersion was appropriately diluted with water at the time of measurement, and the particle size was measured with a wet particle size distribution meter manufactured by Beckman Coulter. The average particle size of the particles in the dispersion was 0.7 μm.

(Example 2: Production of hesperetin dispersion)
Reduced starch saccharified product (manufactured by Towa Kasei Kogyo Co., Ltd .; trade name: Amami; solid content: 70%) 715.1 g of decaglycerin monooleate (manufactured by Taiyo Kagaku Co., Ltd .; trade name: Sunsoft Q-17Y; Deca Glycerol monooleate; hydroxyl value 868; ratio of primary hydroxyl group 59.6%) 10 g, glyceryl monostearate (manufactured by Taiyo Kagaku Co., Ltd .; trade name Sunsoft No. 621B; glyceryl monostearate glycerin 10 g) Enzyme-degraded lecithin (manufactured by Taiyo Kagaku Co., Ltd .; trade name San lecithin A; content of enzyme-decomposed lecithin 100.0; degraded by phospholipase A ₂ ; degradation rate of 50% or more) 0.5 g was added and heated to 80 ° C. and mixed well. Hesperetin (manufactured by Ezaki Glico Co., Ltd .; powder with an average particle size of about 20 μm; purity 90%) and alginic acid ester (manufactured by Kimika Co., Ltd .; trade name Kimiloid NLS-K; alginate esterified with propylene glycol) A degree of esterification of 80%) which was sufficiently mixed with 10 g of powder in advance, 79.4 g of water was further added, and the mixture was uniformly stirred at 80 ° C. This was put into a dyno mill (Shinmaru Enterprises Co., Ltd.), which is a continuous wet grinder, and continuously pulverized for 30 minutes to obtain 714 g of the hesperetin dispersion of the present invention. The dyno mill had a pulverization chamber capacity of 0.6 liter, and 0.48 L of zirconia beads having a diameter of 0.8 mm was used as the pulverization medium.

  The dispersion was appropriately diluted with water at the time of measurement, and the particle size was measured with a wet particle size distribution meter manufactured by Beckman Coulter. The average particle size of the particles in the dispersion was 0.5 μm.

(Example 3: Production of hesperetin dispersion)
Glycerin (manufactured by NOF Corporation; trade name glycerin S; purity 100%) 400.0 g, reduced starch saccharified product (manufactured by Sanei Saccharification Co., Ltd .; trade name Diatom N; solid content 70%) and 315.5 g emulsifier 10 g of decaglycerin monooleate (manufactured by Taiyo Kagaku; trade name Sunsoft Q-17Y; decaglycerin monooleate; hydroxyl value 868; ratio of primary hydroxyl group 59.6%), glyceryl monostearate ( Manufactured by Taiyo Kagaku Co., Ltd .; trade name Sunsoft No. 621B; glyceryl monostearate glycerin 10 g and enzyme-decomposed lecithin (manufactured by Taiyo Kagaku Co. .3%; decomposed by phospholipase _{a 2;} decomposition rate of 50% or higher) and 5g was added and mixed well and heated to 80 ° C.. Hesperetin (manufactured by Ezaki Glico Co., Ltd .; powder with an average particle size of about 20 μm; purity 90%) and alginic acid ester (manufactured by Kimika Co., Ltd .; trade name Kimiloid NLS-K; alginate esterified with propylene glycol) A degree of esterification of 80%) 10 g of powder sufficiently mixed in advance was added, and 79.5 g of water was further added and stirred uniformly at 80 ° C. This was put into Ready Mill (Imex Co., Ltd.), which is a batch type wet grinder, and pulverized for 90 minutes to obtain 632.5 g of the hesperetin dispersion of the present invention. The ready mill had a pulverizing chamber capacity of 2 liters, and 1 L of zirconia beads having a diameter of 0.8 mm was used as the pulverizing medium.

  The dispersion was appropriately diluted with water at the time of measurement, and the particle size was measured with a wet particle size distribution meter manufactured by Beckman Coulter. The average particle size of the particles in the dispersion was 0.8 μm.

(Example 4: Production of hesperetin powder)
105.0 g of decaglycerin monooleate (manufactured by Taiyo Kagaku Co., Ltd .; trade name Sunsoft Q-17Y; decaglycerin monooleate; hydroxyl value 868; ratio of primary hydroxyl group 59.6%) to 795.0 g of water Acid glyceryl monostearate (manufactured by Taiyo Kagaku Co., Ltd .; trade name Sunsoft No. 621B; glyceryl monostearate glycerin) and enzyme-degraded lecithin (manufactured by Taiyo Kagaku Co., Ltd .; trade name of San lecithin A-1; enzyme) The content of decomposed lecithin was 33.3%; decomposed by phospholipase A ₂ ; decomposition rate of 50% or more) was added, and heated to 80 ° C. and mixed well. Hesperetin (manufactured by Ezaki Glico Co., Ltd .; powder with an average particle size of about 20 μm; purity 90%) and alginic acid ester (manufactured by Kimika Co., Ltd .; trade name Kimiloid NLS-K; alginate esterified with propylene glycol) A degree of esterification of 80%) 10 g of powder mixed sufficiently in advance was added and stirred uniformly at 80 ° C. This was put into a dyno mill (Shinmaru Enterprises Co., Ltd.), which is a continuous wet grinder, and continuously pulverized for 30 minutes to obtain 714 g of the hesperetin dispersion of the present invention. The dyno mill had a grinding chamber volume of 0.6 liters, and 0.48 L of zirconia beads having a diameter of 0.8 mm was used as the grinding medium.

  This dispersion was appropriately diluted with water at the time of measurement, and the particle size was measured with a wet particle size distribution meter manufactured by Beckman Coulter. The average particle size of the particles in the dispersion was 0.8 μm.

  Further, this dispersion was spray-dried with an L-8 type spray dryer (Okawara Processing Machine Co., Ltd.) to obtain 146 g of a powder formulation.

(Evaluation Example 1: Confirmation of dispersion stability of dilute dispersion prepared from hesperetin dispersion)
Add 1.765 g of the hesperetin dispersion of Example 1 (hesperetin content 0.3 g), 10 g of fructose-glucose liquid sugar (trade name Hyfructoka 75, Kato Chemical Co., Ltd.) and 0.1 g of citric acid to about 50 ml of water. After stirring, water was further added to make up to 100 ml to obtain a diluted dispersion. The diluted dispersion was placed in a glass bottle and sealed with a metal cap, and then heat sterilized in hot water at 90 ° C. for 20 minutes. No precipitate was observed in the diluted dispersion after heat sterilization, and the dispersion had a homogeneous milky white color. When this glass bottle was divided into two groups, one was allowed to stand at room temperature (about 20-30 ° C.) and the other was left in a refrigerator (about 5 ° C.), no precipitation was observed after 24 hours, and these dispersions were homogeneous. It had a very milky white color. Further, the mixture was allowed to stand under the same conditions. As a result, even after one month of standing, no precipitation was observed at room temperature or in the refrigerator, and these dispersions had a homogeneous milky white color.

  From this, it was found that the dilute dispersion produced using the hesperetin dispersion of the present invention has very excellent dispersion stability.

(Evaluation Example 2: Confirmation of dispersion stability of hesperetin dispersion prepared from the hesperetin powder formulation of the present invention)
Add 0.36 g of the hesperetin powder formulation of Example 4 (hesperetin content 0.3 g), 10 g of fructose-glucose liquid sugar (trade name Hyfructoka 75, Kato Chemical Co., Ltd.) and 0.1 g of citric acid to about 50 ml of water. After stirring, water was further added to make up to 100 ml to obtain a dispersion. The dispersion was placed in a glass bottle and sealed with a metal cap, and then sterilized by heating in hot water at 90 ° C. for 20 minutes. No precipitate was observed in the diluted dispersion after heat sterilization, and the dispersion had a homogeneous milky white color. When this glass bottle was divided into two groups, one was allowed to stand at room temperature (about 20-30 ° C.) and the other was allowed to stand in a refrigerator (about 5 ° C.), no precipitation was observed after 24 hours, and the dispersion was homogeneous. It was milky white. Further, when the mixture was left standing under the same conditions, a little amount of precipitation was observed one month after standing, both at room temperature and in the refrigerator. The amount of this precipitation was the same as in Comparative Evaluation Examples 1 and 2. Very little compared to the amount of precipitation observed. In addition, the dispersion after 1 month of standing had a uniform milky white color.

  From this, it was found that the dispersion produced using the hesperetin powder of the present invention has very excellent dispersion stability.

(Comparative Evaluation Example 1: Hesperetin dispersion prepared from conventional hesperetin powder)
Hesperetin powder (manufactured by Ezaki Glico Co., Ltd .; powder with an average particle size of about 20 μm; purity 90%) 0.3 g, fructose glucose liquid sugar (Kato Chemical Co., Ltd. trade name Hyfructoka 75) 10 g, citric acid 0.1 g Was added to about 50 ml of water and stirred well, and the solution made up to 100 ml by adding water was placed in a glass bottle and sealed with a metal cap, and then heat sterilized in 90 ° C. hot water for 20 minutes. When this glass bottle was divided into two groups, one was allowed to stand at room temperature (about 20-30 ° C.) and the other was allowed to stand in a refrigerator (about 5 ° C.), precipitation of hesperetin was observed immediately after standing.

(Evaluation Example 1A: F Superechin confirmation of the dispersion stability of the dilute dispersion prepared from a dispersion)
Add 1.765 g of the hesperetin dispersion of Comparative Example 1 (hesperetin content 0.3 g), 10 g of fructose glucose liquid sugar (trade name Hyfructoka 75, Kato Chemical Co., Ltd.) and 0.1 g of citric acid to about 50 ml of water. After stirring, water was further added to make up to 100 ml to obtain a diluted dispersion. The diluted dispersion was placed in a glass bottle and sealed with a metal cap, and then heat sterilized in hot water at 90 ° C. for 20 minutes. When this glass bottle was divided into two groups, one was allowed to stand at room temperature (about 20-30 ° C.) and the other was allowed to stand in a refrigerator (about 5 ° C.), precipitation of hesperetin was observed immediately after the standing.

  From this, it was found that even if the particle size of the hesperetin particles was reduced, a stable hesperetin dispersion could not be obtained unless a surfactant was used.

(Evaluation Example 3: Absorption test of hesperetin dispersion of the present invention in mice)
A hesperetin dispersion is obtained by dispersing the hesperetin dispersion of Example 1 in water so that the hesperetin concentration is 5 mg / ml.

  Seven-week-old ddY mice (male) were fed MF (produced by Oriental Yeast Co., Ltd.) as a feed and preliminarily raised for 3 days, and then placed under fasting for 14 hours before test substance administration. Then, 200 μl of hesperetin dispersion (hesperetin concentration: 5 mg / ml) was orally administered. At 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours after administration, blood was collected from the hearts of 5 to 7 mice, and the serum was separated by a conventional method.

  In order to quantify the amount of hesperidin derivative in the collected serum sample, sulfatase H-2 (manufactured by Sigma Aldrich Japan Co., Ltd.) 10 times with acetate buffer (0.1 M, pH 5.0) is used for 50 μl of each serum sample. 50 μl of the diluted product was added and reacted at 37 ° C. for 2 hours. Next, 750 μl of acetonitrile was added to the reaction solution, and the mixture was sufficiently stirred, followed by centrifugation. The supernatant was solidified by concentration centrifugation to obtain a solid. This solid was dissolved in 100 to 400 μl of acetonitrile / methanol / water (50:20:30, v / v / v) and analyzed by high performance liquid chromatography. The concentration of hesperetin in each serum sample was determined by converting hesperetin as a standard. The results are shown in Table 1 and FIG. In addition, the area under the curve (AUC) of 0 to 4 hours of this graph was calculated. The results are shown in Table 2.

Comparative Evaluation Example 3: Conventional Hesperetin Absorption Test in Mice
Hesperetin (Sigma Aldrich Japan Co., Ltd.) 50 mg was added to 10 ml of distilled water to prepare a hesperetin suspension (hesperetin concentration 5 mg / ml). This solution was stirred well and immediately 200 μl was taken and orally administered to 47 ddY mice (male) under the same conditions as in Evaluation Example 3, and the absorbability was measured in the same manner as in Evaluation Example 3. The results are shown in Table 1 and FIG. In addition, the area under the curve (AUC) of 0 to 4 hours of this graph was calculated. The results are shown in Table 2.

(Comparative Evaluation Example 4: Hesperidin Absorption Test in Mice)
Hesperidin suspension was prepared by adding 126 mg of hesperidin (purchased from Sigma-Aldrich Japan Co., Ltd .; purity 80%) to 10 ml of distilled water (101 mg in terms of hesperidin) (hesperetin concentration 5 mg / ml). This solution was stirred well and immediately 200 μl was taken and orally administered to 47 ddY mice (male) under the same conditions as in Evaluation Example 3, and the absorbability was measured in the same manner as in Evaluation Example 3. The results are shown in Table 1 and FIG. In addition, the area under the curve (AUC) of 0 to 4 hours of this graph was calculated. The results are shown in Table 2.

(Comparative Evaluation Example 5: Absorption test of enzyme-treated hesperidin)
Enzyme-treated hesperidin (added with one glucose residue to hesperidin; purchased from Ezaki Glico Co., Ltd .; trade name αG hesperidin PA-T; purity 70%) was added to 10 ml of distilled water to prepare an enzyme-treated hesperidin solution. Prepared (Hesperetin concentration 5 mg / ml). 200 μl of this solution was taken and orally administered to 47 ddY mice (male) under the same conditions as in Evaluation Example 3, and absorbency was measured in the same manner as in Evaluation Example 3. The results are shown in Table 1 and FIG. In addition, the area under the curve (AUC) of 0 to 4 hours of this graph was calculated. The results are shown in Table 2.

(Summary of results of Evaluation Example 3 and Comparative Evaluation Examples 3 to 5)
Table 1 below shows the serum hesperetin concentration (ng / ml) obtained in Evaluation Example 3 and Comparative Evaluation Examples 3 to 5.

As a result, the serum hesperetin concentration 15 minutes after administration of the hesperetin dispersion of the present invention was about 2.8 times the serum hesperetin concentration when hesperetin, hesperidin and enzyme-treated hesperidin were administered, respectively. It was shown to be about 310 times and about 80 times higher concentrations.

  Table 2 below shows the area under the curve (AUC) from 0 to 4 hours after administration of dispersed hesperetin.

In Table 2, the relative ratio indicates the ratio when the AUC of hesperetin is 1.0. When the hesperetin dispersion of the present invention was administered, the AUC (area under blood concentration) of 0 to 4 hours after administration was about 1.4 times that of AUC when hesperetin, hesperidin and enzyme-treated hesperidin were administered. The values were about 55 times and about 15 times higher. From this result, it was found that the absorption efficiency into the body is increased by stably dispersing hesperetin.

(Example 5: Preparation of a hesperetin dispersion beverage)
The materials described in Table 3 below were mixed at the ratio described in Table 3 below to prepare a hesperetin dispersion beverage.

After mixing and dissolving the above materials, a 100 ml capacity aluminum bottle can was filled so that the contents could not be identified from the outside, sealed, and then heat-sterilized in 90 ° C. hot water for 10 minutes.

(Evaluation Example 4 and Comparative Evaluation Examples 6 to 7: Confirmation of blood flow and cooling improvement effect)
(1. Test content)
The subjects were 12 healthy female students aged 19-22. The subjects were explained about the test contents and test methods, and written consent was obtained. The test was conducted within 2 weeks after the end of menstruation for each subject. The test time was from 3 pm to 5 pm or from 5 pm to 7 pm.

  The test food was (1) 100 ml of the hesperetin dispersion beverage prepared in Example 5 (equivalent to 175 mg in terms of hesperetin) (Evaluation Example 4), (2) a beverage containing αG hesperidin (αG hesperidin instead of hesperetin in hesperetin) 100 ml (comparative evaluation example 6), or (3) placebo (except for containing neither αG hesperidin nor hesperetin, except that it contains 175 mg in terms of conversion) (1), (2) 100 ml (comparative evaluation example 7). The test food was subjected to the test at 37 ° C. It was devised so that the subject and the measurer did not know the difference in which test foods were consumed (double blind).

(2. Measurement method)
Body surface temperature measurement and blood flow measurement were performed. The body surface temperature was measured using a skin temperature measuring device (Anritsu Meter) at two locations, “left hand middle finger dorsal side” and “left ankle”. For blood flow measurement, a semiconductor laser blood flow device (ADVANCE, Inc.) was used, and measurement was continuously performed at the “left hand middle finger ventral second joint”.

(3. Test schedule)
The test subjects were allowed to enter the anterior chamber on an empty stomach for at least 3 hours after eating. Thereafter, it was allowed to rest for 30 minutes in order to adapt to room temperature. The subject changed into specified clothes (up and down jersey + T-shirt). After entering the test room, a measuring machine was attached, and body surface temperature measurement, tympanic temperature measurement, and blood flow measurement were started. The apparatus was mounted within 10 minutes after entering the room, and then the test food) was ingested 10 minutes after entering the room, followed by continuous measurement for 72 minutes. This schedule is shown in FIG.

(4. Environmental conditions of the measurement room)
The room temperature of the front chamber is 23 ° C. ± 0.5 ° C., the room temperature of the test chamber is 21.5 (20.7-21.5) ° C., and both the front chamber and the test chamber have a relative humidity of 50% ± 10 %Met.

(5. Other instructions)
Subjects were instructed to rest during the study, and private language and dozing were strictly prohibited. In addition, he was especially strict about resting his left hand. During the test, care was taken that the tip of the left hand did not touch the desk or cloth.

(6. Results)
As typical results, the blood flow change amount (ml / min) of the left hand middle finger ventral side second joint is shown in Table 4, the change amount (° C.) of the surface temperature of the left hand fingertip (middle finger back side) in Table 5, Table 6 shows the amount of change in the surface temperature of the left ankle (° C.). All of these figures are averages of 12 subjects.

Regarding the fingertip blood flow at 9 minutes, 14 minutes, and 30 minutes after ingestion, when hesperetin dispersion was used, the amount of increase in blood flow was greater than that of αG hesperidin and placebo.

  With respect to the surface temperature of the fingertips at 9 minutes, 14 minutes, 30 minutes and 60 minutes after ingestion, compared with the placebo or αG hesperidin when using the hesperetin dispersion The temperature rise was high. After 60 minutes, when αG hesperidin was used, the temperature rise was almost the same as that of placebo, and when hesperetin dispersion was used, the value was higher than that of placebo.

  At the ankle surface temperature, at 9 and 14 minutes after ingestion, when hesperetin dispersion is used, the decrease in body temperature is suppressed as compared with the case where placebo or αG hesperidin is used. 30 minutes after ingestion, the decrease in body temperature is suppressed when αG hesperidin is used as compared with the placebo even when hesperetin dispersion is used. After 60 minutes, when hesperetin dispersion or αG hesperidin was used, the decrease in body temperature was suppressed as compared to placebo. However, when hesperetin dispersion was used, body temperature was significantly higher than when αG hesperidin was used. The decrease is suppressed.

(Evaluation Example 5: Human absorbability test of the hesperetin dispersion of the present invention)
The hesperetin dispersion (hesperetin content 17%) prepared according to Example 1 was diluted with water to a hesperetin concentration of 3 mg / ml, and then mixed well to obtain a dispersed hesperetin solution. More specifically, 1765 mg of hesperetin dispersion prepared according to Example 1 was diluted with 100 g of water. As a control, 300 mg of hesperetin was diluted with 100 g of water.

  Five healthy adult male subjects were fasted after 9:30 pm the previous day, and 100 ml of dispersed hesperetin solution (hesperetin content 300 mg) was ingested at 9:30 am. About 5 ml of blood was collected from the brachial vein at the time of ingestion (0 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours after the intake, Serum was separated by centrifugation. A similar test was conducted using the hesperetin solution after a period of 3 days or more from the time of ingestion of the dispersed hesperetin solution.

  In order to quantify the amount of hesperidin derivative in the collected serum sample, 500 μl of acetate buffer (0.1 M, pH 4.5) was added to 500 μl of each serum sample. Further, 100 μl of sulfatase H-2 (manufactured by Sigma Aldrich Japan Co., Ltd.) diluted 10-fold with an acetate buffer (0.1 M, pH 5.0) was added and reacted at 37 ° C. for 2 hours. Next, 500 μl of oxalic acid (0.01 M) was added, and after sufficient stirring, the mixture was centrifuged, and the supernatant was loaded onto Oasis HLB 30 mg / 1 cc (manufactured by Nihon Waters Co., Ltd.) that had been equilibrated. After washing with 1 ml of oxalic acid (0.01M) and 1 ml of water, elution was performed with 1 ml of methanol. This was solidified by concentration centrifugation. 200 μl of acetonitrile was added thereto, stirred, and then sonicated for about 15 minutes to dissolve hesperetin. After centrifuging this solution, the supernatant was subjected to high performance liquid chromatography and analyzed using an electrochemical detector (Colochem III manufactured by ESA). The concentration of hesperetin in each serum sample was determined by converting hesperetin as a standard. The results are shown in Table 7 below.

From this result, a graph of blood concentration was prepared, and the area under the curve (AUC) from 0 to 8 hours of this graph was calculated. The graph is shown in FIG. 3, and the calculation result of the area under the curve is shown in Table 8 below.

Therefore, when the area under the curve when hesperetin was ingested was converted to 1, the area under the curve when hesperetin dispersion was ingested was about 3.5 times. That is, by using hesperetin as the hesperetin dispersion of the present invention, the amount of absorption was improved about 3.5 times.

  As a result, the amount of hesperetin absorbed when the dispersed hesperetin solution was ingested was significantly higher than that when hesperetin was ingested. Therefore, in humans, as in the results of the mouse in Evaluation Example 3, it was found that the absorption is improved by stably dispersing hesperetin. Furthermore, in mice, the amount of absorption was improved by about 3.5 times in humans compared to the increase in absorption by about 1.4 times by using hesperetin as a hesperetin dispersion. And found that better results were obtained.

(Evaluation Example 6 and Comparative Evaluation Examples 8-1 to 8-3: Collagen production inducing action confirmation test)
In order to examine the effect of the hesperetin dispersion on collagen production of human dermal fibroblasts, first, normal human dermal fibroblasts (NB1RGB strain) were placed in a 96-well plate at 2.5 × 10 ⁴ cells / well. Seed and in 200 μl of DMEM liquid medium (DMEM medium containing 584 mg / L L-glutamine, 4% FBS, 1% penicillin-streptomycin (containing 1 mg / L glucose (GIBCO)) at 37 ° C., 5% CO ₂ And preincubated overnight. After removing the medium, the DMEM medium (DMEM medium containing 584 mg / L L-glutamine, 4% FBS, 1% penicillin-streptomycin (containing 1 mg / L glucose) (GIBCO) so that the concentration in terms of hesperetin is 50 μM. ) Was added to each well. As samples, a hesperetin dispersion (Evaluation Example 6), hesperetin (Comparative Evaluation Example 8-1), hesperidin (Comparative Evaluation Example 8-2) and an additive-free group (Comparative Evaluation Example 8-3) were used. As the hesperetin dispersion, the hesperetin dispersion prepared in Example 1 was used. After culturing at 37 ° C. under 5% CO ₂ for 72 hours, the medium was collected. Human collagen type I ELISA (AC Biotechnology Co., Ltd.) was used to quantify the amount of collagen in this medium. The results are shown in Table 9 below.

As a result, the collagen production amount in the non-added group (medium only) was 3.65 μg / ml, but when the hesperetin dispersion was added, the collagen production amount was 5.26 μg / ml (about 140% of the non-added group). ) And collagen-inducibility was observed. Moreover, this collagen production amount is about 120% compared with the case where the conventional hesperetin is added, and the collagen inductivity remarkably superior to the conventional hesperetin was recognized.

(Example 5 and Comparative Example 2 Preparation of external preparation containing dispersed hesperetin and confirmation test of its effect)
(1) Preparation of external preparation containing dispersed hesperetin First, dispersed hesperetin powder was produced. 105.0 g of decaglycerin monooleate (manufactured by Taiyo Kagaku Co., Ltd .; trade name Sunsoft Q-17Y; decaglycerin monooleate; hydroxyl value 868; ratio of primary hydroxyl group 59.6%) to 795.0 g of water Acid glyceryl monostearate (manufactured by Taiyo Kagaku Co., Ltd .; trade name Sunsoft No. 621B; glyceryl monostearate glycerin 10 g and enzyme-degraded lecithin (manufactured by Taiyo Kagaku Co., Ltd .; trade name Sanrecitin A-1) Content of lecithin 33.3%: Decomposed by phospholipase A ₂ ; Decomposition rate 50% or more 5 g was added and mixed well by heating to 80 ° C. Hesperetin (manufactured by Ezaki Glico Co., Ltd .; average particle size 20 μm) 170g of powder with a purity of 90% and alginic acid ester (manufactured by Kimika Co., Ltd .; trade name Kimiloid NLS-K; alginic acid) Esterified with propylene glycol; degree of esterification 80%) and 0.4 g of sodium bicarbonate sufficiently mixed in advance were added and stirred uniformly at 80 ° C. This was performed with a continuous wet grinder. It was put into a certain dyno mill (Shinmaru Enterprises Co., Ltd.) and continuously pulverized for 30 minutes to obtain 714 g of the hesperetin dispersion of the present invention, where the pulverizing chamber capacity of the dyno mill is 0.6 liter, As a grinding medium, 0.48 L of zirconia beads having a diameter of 0.8 mm was used.

  This dispersion was appropriately diluted with water at the time of measurement, and the particle size was measured with a wet particle size distribution meter manufactured by Beckman Coulter. The average particle size of the particles in the dispersion was 0.8 μm.

Further, this dispersion was spray-dried with an L-8 type spray dryer (Okawara Processing Machine Co., Ltd.) to obtain 146 g of a powder formulation. This powder formulation (dispersed hesperetin powder) has the following composition:
Hesperetin 82.7% by weight
Emulsifier 12.2% by weight
Stabilizer 4.9% by weight
Sodium bicarbonate 0.2% by weight
(Emulsifier: decaglycerin monooleate + glyceryl monostearate + enzymolytic lecithin;
Stabilizer: alginate).

  A dispersion in which this powder formulation (dispersed hesperetin powder) was dispersed in 3 times the amount of distilled water was prepared and used as a test solution (Example 5). The hesperetin content of this dispersion was 20.7%. This dispersion is an example of a skin external preparation. As a control group (placebo solution), distilled water was used (Comparative Example 2).

  (2) The following test was carried out using the above test solution and the control group.

(2-1) Examination of skin quality improvement effect <Test method>
The measurement sites were the upper arm and wrist, and the test period was 4 weeks. The test solution was applied to the upper arm and wrist of one arm, and the placebo solution was applied to the upper arm and wrist of another arm twice a day in the morning and evening. The application amount of the test solution and the placebo solution was 100 mg / time, respectively. Before and during ingestion, the amount of water, the amount of water transpiration, the amount of melanin and the elasticity were measured every week.

  During the measurement, the test subject was thoroughly washed with soap. In order to keep the measurement conditions the same as much as possible, after having the subject wait for 20 minutes or more in a test room set at a constant environment of room temperature 24 ° C. and relative humidity 50%, water content, elasticity, water evaporation and The amount of melanin was measured. The amount of water was measured using “Corneometer CM825 (Courage + Khazaka Electronic GmbH)”. The elasticity was measured using “Cumeter SEM575 (Courage + Khazaka Electronic GmbH)”. Moisture transpiration was measured using "Teweter TM300 (Courage + Khazaka Electronic GmbH)". Melanin was measured using “Mexameter MX18 (Courage + Khazaka Electronic GmbH)”.

<Test results>
The number of subjects was 3 healthy adult women. The results are shown in Tables 10-14 below. All the results show the numerical value at the time of measurement when the numerical value before coating is 100, expressed as a percentage (%).

In both the upper arm and wrist, the amount of water in the test solution group improved compared to the placebo group. That is, it was found that the test liquid group is more effective in improving skin moisture.

In both the upper arm and wrist, the amount of water transpiration was lower in the test solution group than in the placebo group. That is, it was found that the test liquid group is more effective in improving the skin barrier property.

In both the upper arm and wrist, the amount of melanin was lower in the test solution group than in the placebo group. In the placebo group, the amount of melanin on the wrist increased, whereas in the test solution group, the amount of melanin on the wrist decreased. In the placebo group, the amount of melanin in the upper arm did not change, whereas in the test solution group, the amount of melanin in the upper arm decreased. This clearly shows the whitening effect of the test solution group of the present invention in the upper arm portion that is not exposed to sunlight. Moreover, it is thought that the effect | action of both the sunburn prevention effect and the whitening effect by the test liquid group of this invention is exhibited in the wrist which receives sunlight.

In both the upper arm and wrist, the test solution group improved the softness of the skin compared to the placebo group.

In both the upper arm and wrist, the test solution group improved the softness of the skin compared to the placebo group.

  From these results, it was clarified that the external preparation for skin of the present invention has an excellent action in a moisturizing effect, a melanin suppressing effect, a skin tone and the like.

(2-2) Examination of blood flow improvement and temperature recovery effect <Test method>
A test for investigating the effects of application of the test solution on blood flow and skin temperature was conducted in a test room at room temperature of 25 ° C. The subject was allowed to rest for at least 10 minutes after entering the room and confirmed that the blood flow at the fingertips was stable. Thereafter, 50 mg of the test solution was applied to each middle finger, ring finger, and little finger of one hand, and 50 mg of placebo solution was applied to each middle finger, ring finger, and little finger of another hand. A temperature sensor was attached to the first joint of the middle finger, ring finger, and little finger, and the skin temperature was recorded. Blood flow was measured at the belly of the finger between the first joint of the ring finger and the fingertip. After 10 minutes had passed since the emulsified hesperetin solution or placebo solution was applied, a polyethylene glove was put on and a cooling load was applied in which hands were immersed in water at 10 ° C. for 1 minute. The skin temperature and blood flow were continuously measured in the same manner for 20 minutes after the cooling load. For measurement of skin temperature, COMPACT THERMO LOGGER AM-8000K (Anritsu Keiki Co., Ltd.) was used, and laser blood flow meter (Omega Wave FLO-N1) was used for measurement of blood flow.

<Result>
The number of subjects was 3 healthy adult women.

Change in blood flow The time taken for the blood flow reduced by the cooling load to recover to the resting blood flow before application of the sample was used as an indicator of blood flow change. The average values of three subjects were compared.

As a result, it was found that the test solution group recovered blood flow about twice as fast as the placebo group.

Temperature change The time taken for the body temperature reduced by the cooling load to recover to the resting body temperature before the sample application was used as an index of temperature change. Comparison was made with an average of three subjects.

As a result, it was found that the temperature of the test solution group recovered faster than that of the placebo group. This effect is thought to be due to the rapid recovery of blood flow.

(Evaluation Examples 7-1 and 7-2 and Comparative Evaluation Example 9: Cooling load test result by ingestion of hesperetin dispersion)
The test method is as follows:
(1. Test content)
Subjects were 3 healthy adult women.

(2. Test drink)
A sample similar to the hesperetin dispersion beverage prepared in Example 5 (Table 3) was used as an ingestion sample. Beverages in the test group (evaluation examples 7-1 and 7-2) to which the hesperetin dispersion was added so that the hesperetin content was 125 mg or 50 mg, and beverages in the placebo group to which no dispersion was added (comparative evaluation example 9) were prepared. did. The ingredients of the placebo group beverage were the same as the test group beverage except that it did not contain the hesperetin dispersion. The test beverage was subjected to the test at 37 ° C. It was devised so that the subject and the measurer did not know the difference in which test drinks were taken (double blind).

(3. Environmental conditions of the measurement room)
The room temperature of the front chamber is 23 ° C. ± 0.5 ° C., the room temperature of the test chamber is 21.5 (20.7-21.5) ° C., and both the front chamber and the test chamber have a relative humidity of 50% ± 10 %Met.

(4. Test schedule)
The test subjects were allowed to enter the anterior chamber on an empty stomach for at least 3 hours after eating. Then it was allowed to rest for 10 minutes in order to adapt to room temperature. The test beverage was orally ingested and then rested for 20 minutes. Next, the left hand was immersed in cold water at 15 ° C. for 1 minute to cool the wrist. Subsequently, the hand was taken out from the cold water to remove the water in a short time. Body temperature was measured up to 40 minutes every 5 minutes with the time taken out of the cold water as 0 minutes. The body temperature measurement site was near the first joint of the five fingers on the left back side. An average value of 5 fingers was obtained. The measurement site on the obtained thermograph is shown in FIG. Measurement was performed with a measuring device (infrared thermotracer TH9100 (manufactured by NEC Sanei)), and data processing was performed using analysis software (thermal image processing program TH91-702 (manufactured by NEC Sanei)).

(5. Measurement results)
The measurement results are shown in Table 17 below and FIG.

As a result, in both cases where the hesperetin content was 50 mg and 125 mg, the surface temperature suddenly increased from about 5 minutes after the cooling, and after 10 minutes, the body temperature almost recovered before the cooling. On the other hand, in the case of placebo, body temperature did not recover until about 30 minutes after cooling.

  As mentioned above, although this invention has been illustrated using preferable embodiment of this invention, this invention should not be limited and limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range based on the description of the present invention and the common general technical knowledge from the description of specific preferred embodiments of the present invention. Patents, patent applications, and documents cited herein should be incorporated by reference in their entirety, as if the contents themselves were specifically described herein. Understood.

  Since the hesperetin dispersion of the present invention is a stable hesperetin dispersion, it can be suitably used for foods that are stored for a long period of time, particularly beverages. Since the powder of the present invention can be effectively used for producing such a hesperetin dispersion, it can be widely used. Since the hesperetin dispersion and the powder of the present invention have improved absorbability to living bodies compared to conventional hesperetin, they can be suitably used for various applications.

FIG. 1 shows administration of the hesperetin dispersion of Example 1 (Evaluation Example 3), a conventional hesperetin suspension (Comparative Evaluation Example 3), hesperidin (Comparative Evaluation Example 4) or enzyme-treated hesperidin (Comparative Evaluation Example 5). It is a graph which shows the hesperetin density | concentration in the serum of a mouse | mouth. FIG. 2 is a diagram schematically showing the test schedule used in Evaluation Example 4 and Comparative Evaluation Examples 6-7. FIG. 3 is a graph showing the concentration of hesperetin in human serum administered with a hesperetin dispersion or a conventional hesperetin suspension. FIG. 4 is a graph showing the collagen production effect of a hesperetin-related substance. FIG. 5 is a thermograph showing measurement sites of body surface temperature. The body surface temperature was measured at the points marked with “A” to “E”. FIG. 6 shows the results of a cooling load test in Example 7. FIG. 7 shows a dispersion model diagram of the hesperetin preparation.

Claims (30)

A hesperetin dispersion containing hesperetin particles, a surfactant and a solvent, and further containing a polysaccharide, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, hesperetin dispersion.   The dispersion according to claim 1, wherein the surfactant comprises an enzymatically degraded lecithin.   The dispersion liquid according to claim 1, wherein the surfactant comprises glycerin fatty acid organic acid ester and enzyme-degraded lecithin.   The dispersion according to claim 1, wherein the polysaccharide is selected from the group consisting of alginic acid and alginic acid ester.   The dispersion according to claim 1, wherein the polysaccharide is an alginate. Wherein the polysaccharide is alginate, the dispersion of claim 2. Wherein the polysaccharide is alginate, dispersion of claim 3.   The dispersion liquid of Claim 1 whose average particle diameter of the said hesperetin particle | grain is 0.1 micrometer-10 micrometers.   The dispersion according to claim 1, wherein the content of hesperetin particles in the hesperetin dispersion is 1 wt% to 50 wt%. A powder comprising hesperetin particles and a surfactant and further comprising a polysaccharide, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, powdered.   The powder according to claim 10, wherein the surfactant comprises enzymolytic lecithin.   The powder according to claim 10, wherein the surfactant comprises glycerin fatty acid organic acid ester and enzyme-degraded lecithin.   The powder according to claim 10, wherein the polysaccharide is selected from the group consisting of alginic acid and alginic acid ester.   The powder according to claim 10, wherein the polysaccharide is an alginate.   The powder according to claim 11, wherein the polysaccharide is an alginate.   The powder according to claim 12, wherein the polysaccharide is an alginate.   The powder of Claim 10 whose average particle diameter of the said hesperetin particle | grain is 0.1 micrometer-10 micrometers.   The powder of Claim 10 whose content of the hesperetin particle | grains in the said powder is 30 weight%-95 weight%. A food or drink comprising hesperetin particles and a surfactant, and further comprising a polysaccharide, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically decomposed lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, food. A quasi-drug containing hesperetin particles and a surfactant, and further containing a polysaccharide, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, quasi drugs. A pharmaceutical comprising hesperetin particles and a surfactant, and further comprising a polysaccharide, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, pharmaceuticals. A skin external preparation containing hesperetin particles and a surfactant, and further containing a polysaccharide, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester, and an enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, external preparation for skin. A bathing agent comprising hesperetin particles and a surfactant, and further comprising a polysaccharide, wherein the surfactant is selected from the group consisting of a polyglycerin fatty acid ester, a glycerin fatty acid organic acid ester and an enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, bath salts. A feed comprising hesperetin particles and a surfactant, and further comprising a polysaccharide, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, feed. A pet food comprising hesperetin particles and a surfactant, further comprising a polysaccharide, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, pet food. A fiber comprising hesperetin particles and a surfactant, and further comprising a polysaccharide, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, fibers. A garment comprising hesperetin particles and a surfactant and further comprising a polysaccharide, wherein the surfactant is selected from the group consisting of polyglycerin fatty acid ester, glycerin fatty acid organic acid ester and enzymatically degraded lecithin ,
Here, the polysaccharide is alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth, Ru is selected from karaya and pectin, clothing. A method for producing a hesperetin dispersion according to claim 1, wherein the method comprises:
Mixing a hesperetin bulk powder, the surfactant, a solvent, and a polysaccharide to obtain a mixture; and crushing the mixture with a wet grinder to obtain a hesperetin dispersion ,
Wherein the polysaccharide is selected from alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth gum, karaya gum and pectin . The method for producing a powder according to claim 10, wherein the method comprises:
Mixing the hesperetin bulk powder, the surfactant, the solvent and the polysaccharide to obtain a mixture;
Crushing the hesperetin bulk powder in the mixture by subjecting the mixture to a wet grinder to obtain a hesperetin dispersion; and drying the hesperetin dispersion to obtain a hesperetin powder .
Wherein the polysaccharide is selected from alginic acid, alginate, carrageenan, guar gum, locust bean gum, xanthan gum, gum arabic, tragacanth gum, karaya gum and pectin .   30. The method of claim 29, wherein the drying is performed by lyophilization.