JP2013177340A - Anti-inflammatory agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an anti-inflammatory agent stronger than resveratrol and ferulic acid, and furthermore, foods, cosmetics, medicines and quasi drugs containing the anti-inflammatory agent.SOLUTION: There is provided at least one kind of compounds selected from the group consisting of newly synthesized specific resveratrol derivatives which are polyphenols and pharmaceutically permissible salts thereof.

Description

  The present invention relates to an anti-inflammatory agent and foods, cosmetics, pharmaceuticals and quasi drugs containing the same, and in particular, an anti-inflammatory agent containing a resveratrol derivative as an active ingredient, and foods and cosmetics containing the same, It relates to pharmaceuticals and quasi drugs.

In recent years, due to lifestyle changes and increased stress, the number of patients with inflammatory diseases such as chemical hypersensitivity, hay fever, atopic dermatitis and psoriasis has been increasing.
Many of these inflammatory diseases are known to be caused by abnormal production of endogenous cytokines typified by human tumor necrosis factor-α (hTNF-α). Several proposals have been made. For example, Patent Document 1 and Patent Document 2 propose an anti-inflammatory agent containing an extract from a tree such as dog larch and tablin as an active ingredient, and Patent Document 3 discloses a peptide having an anti-inflammatory action or an acid addition salt thereof. And an anti-inflammatory agent containing a carrier, Patent Document 4 discloses an extract of plant seeds belonging to the genus Vitis, mushrooms belonging to the genus Fuscoporia, and pericarp of plants belonging to the genus Malus. Type 2 helper T-cell cytokine production inhibitor, Patent Document 5 discloses bamboo leaves, mugwort, cedar leaves, mint, loofah, birch, grape seeds, gambling, gymnema, guava, wolfberry, kumazasa, jasmine, sugina, Dokudami, pearl barley, loquat leaves, morohaya, udo, saffron, mulberry, ruffma, safflower, eucommia, lily of the valley Th2 cytokine expression inhibitor as an active ingredient a flavonoid compound extracted from plants such as the mainspring is proposed.

  In addition, there is a report that stilbene derivative resveratrol contained in grape skin and the like, and compounds such as ferulic acid contained in a large amount in the skin layer of rice bran and potato have an inhibitory effect on inflammatory cytokine production (Non-Patent Document 1). 2).

  However, for example, bark extract is unsuitable for oral intake due to lack of eating experience, and the activity derived from plants derived from eating experience is not sufficient. No further improvement is required.

JP 2000-226323 A Japanese Patent No. 4315255 Japanese Patent No. 4278028 JP 2004-75619 A JP 2001-114686 A

Biochem Pharmacol. 1999 Apr 15; 57 (8): 941-9. J. et al. Clin. Biochem. Nutr. 40, (2) 92-100 (2007)

  As a result of searching for resveratrol derivatives having stronger physiological activity in view of the above situation, the present inventors combined resveratrol and ferulic acid as precursors, and synthesized resveratrol derivatives, Compared with these precursors, they have found a strong anti-inflammatory action and have completed the present invention.

  Therefore, an object of the present invention is to provide an anti-inflammatory agent superior to resveratrol and ferulic acid. Another object of the present invention is to provide foods, cosmetics, pharmaceuticals, and quasi drugs containing the inflammatory agent.

The gist of the present invention is as follows.
[1] Formula (1):

And formula (2):

An anti-inflammatory agent comprising, as an active ingredient, at least one compound selected from the group consisting of a resveratrol derivative represented by the formula: and a pharmaceutically acceptable salt thereof,
[2] The present invention relates to a food, cosmetic, pharmaceutical product or quasi-drug containing the anti-inflammatory agent described in [1].

The resveratrol derivative used in the present invention or a pharmaceutically acceptable salt thereof (hereinafter referred to as resveratrol derivative) has an excellent anti-inflammatory effect compared to the resveratrol and ferulic acid precursors. Therefore, it is useful as a novel anti-inflammatory agent.
The anti-inflammatory agent of the present invention can be suitably used for foods, cosmetics, pharmaceuticals or quasi drugs.

  Hereinafter, the present invention will be described in detail.

Resveratrol derivative used in the present invention,
Formula (1):

Formula (2):

It is a compound represented by these.

  In the resveratrol derivative, the carbon-carbon double bond may be trans or cis, and the resveratrol derivative includes a mixture of a cis isomer and a trans isomer.

  Examples of the pharmaceutically acceptable salt of the resveratrol derivative include alkali metal salts such as lithium salt, sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt, calcium salt and barium salt; aluminum salt Metal hydroxide salts such as aluminum hydroxide salts; amines such as alkylamine salts, dialkylamine salts, trialkylamine salts, alkylenediamine salts, cycloalkylamine salts, arylamine salts, aralkylamine salts, and heterocyclic amine salts Salts; amino acid salts such as α-amino acid salts and ω-amino acid salts; peptide salts or primary, secondary, tertiary, or quaternary amine salts derived therefrom. These pharmacologically acceptable salts can be used alone or in admixture of two or more.

The resveratrol derivative can be obtained by heat-treating a raw material compound such as resveratrol or ferulic acid in the presence of a metal salt.
The raw material compound may be naturally derived or may be a chemically synthesized chemical product with high purity. The naturally occurring raw material compound does not need to be completely purified, and a mixture containing each raw material compound can also be used. The raw material compounds also include derivatives such as salts and esters. In the present invention, these derivatives can also be used as raw materials.
Examples of the derivative of the raw material compound include salts such as sodium salt, potassium salt and calcium salt, and esters such as methyl ester and ethyl ester.
However, from the viewpoint of increasing the production efficiency and recovery rate of the resveratrol derivative, a mixture containing 5% by weight or more in total of the raw material compounds is desirable as a raw material.

  The raw material compound is dissolved in a suitable solvent. At this time, since the solubility of the raw material compound in water is extremely low if the solvent is only water, the raw material compound may be dissolved only in a mixed solution of water and an organic solvent or only in the organic solvent. In this case, there is no restriction | limiting in particular in the compounding ratio of water and an organic solvent, and the kind of organic solvent, and a raw material compound should just fully melt | dissolve. Among them, it is preferable from the viewpoint of safety and cost to use a solvent containing only methanol or ethanol, or a mixed solution of water and methanol or water and ethanol. When the composition (reactant) after the reaction containing the raw material compound is used in foods without being sufficiently purified, it is desirable to use ethanol or hydrous ethanol as a solvent from the viewpoint of safety and legal regulations.

  There is no restriction | limiting in particular in the density | concentration of the raw material compound in the solution containing the raw material compound obtained as mentioned above. For example, there is a merit that the higher the concentration of the raw material compound, the smaller the amount of the solvent used, and so the concentration of the raw material compound is preferably adjusted to be close to the concentration at which each solvent is saturated.

  In the present invention, a metal salt is added to a solution containing the raw material compound (hereinafter referred to as a raw material solution) in order to react the raw material compound to obtain the desired resveratrol derivative.

The metal salt may be any of an acid salt, a basic salt, and a normal salt, and may be any of a single salt, a double salt, and a complex salt. Furthermore, the metal salt may be one kind or a mixture of plural kinds. As an example of the metal salt, those approved as food additives are preferable in terms of safety. For example, magnesium salt, calcium salt, sodium salt, potassium salt, zinc salt, copper salt and the like that are permitted to be added to foods can be mentioned.
Moreover, as a mixture of the metal salts, for example, a mineral premix (Tanabe Seiyaku Co., Ltd., a mineral mixture mainly composed of zinc gluconate, ammonium iron citrate, calcium lactate, copper gluconate, and magnesium phosphate) And a mixture containing several kinds of metal salts. Moreover, mineral water can also be mentioned as a mixture containing a some metal salt.
The content of the metal salt in the raw material solution is not particularly limited as long as it is an amount capable of producing the target resveratrol derivative.

In the presence of the metal salt, the reaction for producing a resveratrol derivative proceeds under acidic conditions or alkaline conditions.
However, it is desirable to appropriately select the reaction conditions in consideration of the purpose of use and purification of the obtained resveratrol derivative, the presence or absence of isolation work, and the taste in the case of addition to food.

  Next, the raw material solution is heat-treated in the presence of a metal salt. By this heat treatment, a reaction for producing the desired resveratrol derivative is performed. In order to efficiently advance the production reaction, it is preferable to adjust the heating temperature of the raw material solution to 90 ° C. or higher. Moreover, it is desirable to perform pressure heating considering the boiling point of the solvent used. For example, the raw material solution is put in an open container and the container is heated at a high temperature exceeding the boiling point of the solvent, the raw material solution is put in a sealed container and the container is heated, and heated under pressure using a retort device or an autoclave. Heating is preferably performed so that the solution temperature reaches 90 ° C. or higher at least partially. From the viewpoint of increasing the production efficiency and recovery efficiency of the desired resveratrol derivative, it is more preferable that the solution temperature be uniformly 90 ° C to 150 ° C. The heating time is not limited as in the case of the heating temperature, and may be a time condition in which the target reaction efficiently proceeds. In particular, the heating time depends on the balance between the heating temperature and the amount of solvent, and it is desirable to set the heating time according to the heating temperature and the amount of solvent. For example, when heating the raw material solution at around 130 ° C., it is preferable to perform heating for 5 minutes to 24 hours after the solution temperature reaches 130 ° C. Further, the heating may be performed once or may be repeated repeatedly in a plurality of times. When heating the raw material solution in a plurality of times, it is preferable to carry out by adding only a solvent or a solvent containing a metal salt.

  The completion of the reaction for producing the resveratrol derivative by the heat treatment may be judged by, for example, confirming the production amount of the resveratrol derivative by component analysis by HPLC described in Examples described later.

  In addition, when the resveratrol derivative is produced by a process using only safe raw materials, it is used in foods, pharmaceuticals, quasi-drugs or cosmetics as described later in a mixture containing the resveratrol derivative. Is possible. For example, when a naturally occurring raw material compound is dissolved in a water-containing ethanol solvent and heated using mineral water or a mineral premix, the resulting liquid reactant can be used as one of the food ingredients. is there.

  In addition, when it is desired to improve the flavor and further enhance the functionality, the reaction product can be concentrated to increase the concentration of resveratrol derivative, or the reaction product can be purified to obtain a pure product of resveratrol derivative. . The concentration and purification can be performed by a known method. For example, the resveratrol derivative can be concentrated by extraction using a solvent extraction method such as chloroform, ethyl acetate, ethanol, or methanol, or a supercritical extraction method using carbon dioxide gas. It is also possible to perform concentration and purification using column chromatography. For the concentration and purification, a membrane treatment method such as a recrystallization method or an ultrafiltration membrane can be used.

  When the resveratrol derivative is separated and recovered from the reaction product, column chromatography, HPLC, or the like may be used.

  Moreover, a powdery solid can be obtained by removing the solvent by subjecting the concentrate or purified product to reduced-pressure drying or freeze-drying as necessary.

  Since the safety of the raw material compound used in the present invention has already been generally confirmed, it is considered that the resveratrol derivative obtained in the present invention is also excellent in safety.

All the resveratrol derivatives obtained as described above have a stronger anti-inflammatory action than resveratrol and ferulic acid which are raw materials.
Therefore, an anti-inflammatory agent containing the resveratrol derivative as an active ingredient can be provided.

  The anti-inflammatory agent may contain only the resveratrol derivative. However, the resveratrol derivative may be a solution obtained by dissolving the resveratrol derivative in a solvent such as ethanol or an ethanol-containing aqueous solution, or an emulsion or suspension by a known method. It may be used as an agent. The content of the resveratrol derivative in the anti-inflammatory agent may be 0.001% by weight or more.

  Moreover, the anti-inflammatory agent of this invention can also be mix | blended and used for foodstuffs, cosmetics, a pharmaceutical, a quasi-drug, etc.

  The food may be in any form such as beverage, alcoholic beverage, jelly, confectionery, and the like. Examples of the confectionery include hard candy, soft candy, gummy candy, and tablet that are excellent in storage and carrying because of their capacity and the like, but are not particularly limited. Further, by adding a novel resveratrol derivative to wine, it is possible to obtain a new wine that further enhances the health function effect of the wine. Like this new wine, food and drink with both palatability and health function effects are food and drink with extremely high social needs that can fully meet the growing needs of health. It is a product. Moreover, since the new resveratrol derivative has an anti-inflammatory action as described later, it is made into a hard candy, soft candy, gummy candy, tablet, etc. that can be easily ingested for the purpose of mitigating inflammation in the oral cavity. Can do. The food includes functional food, health food, health-oriented food, and the like.

  Examples of the cosmetics include skin care products such as creams, lotions, solutions, aerosols, soaps, shampoos, rinses and facial creams.

  Examples of the pharmaceutical include solid preparations such as powders, tablets, pills, capsules, fine granules and granules, liquids such as liquids, suspensions and emulsions, gels and the like. Tablets, pills, fine granules, granules, and capsules containing granules can be sugar-coated with sugars such as sucrose and sugar alcohols such as maltitol, as necessary, and gelatin, hydroxypropyl cellulose, hydroxy It may be coated with propylmethylcellulose or the like, or may be coated with a film of a gastric or enteric substance. Moreover, in order to improve the solubility of a formulation, the said formulation can also be given a known solubilization process. Based on a conventional method, the liquid preparation may be used in the form of an injection or infusion.

  Examples of the quasi-drug include quasi-drugs used in the oral cavity, such as toothpaste, mouthwash, and mouth rinse.

When preparing foods, cosmetics, pharmaceuticals or quasi-drugs using the anti-inflammatory agent of the present invention, ingredients usually used for foods, cosmetics, pharmaceuticals or quasi-drugs within a range not impairing the effects of the present invention Can be blended as appropriate.
For example, in the case of food, food such as water, alcohol, starch, protein, fiber, carbohydrate, lipid, vitamin, mineral, flavoring, coloring, sweetener, seasoning, stabilizer, preservative Can be combined with raw materials or materials usually blended in
In the case of cosmetics, pharmaceuticals or quasi-drugs, the main agent, base material, surfactant, foaming agent, wetting agent, thickener, clearing agent, flavoring agent, coloring agent, stabilizer, preservative, bactericidal agent Etc., based on a conventional method, it can be made into a liquid, ointment-like or sprayable final form.

  When the anti-inflammatory agent of the present invention is added to food, it is usually preferable to add 0.001 to 20% by weight based on the food.

  When the anti-inflammatory agent of the present invention is used for pharmaceutical purposes, for example, the amount of intake thereof is not particularly limited as long as the desired improvement, treatment or prevention effect is obtained. , Sex, constitution and other conditions, the type and degree of disease, and the like. About 0.1 mg to about 1,000 mg per day is preferable, and this can be taken in 1 to 4 times a day.

  When adding the anti-inflammatory agent of this invention to cosmetics or a quasi-drug, it is preferable to add normally 0.001-30 weight% in this quasi-drug.

  Moreover, since the anti-inflammatory agent of the present invention is excellent in safety, not only for humans, for example, non-human animals such as rats, mice, guinea pigs, rabbits, sheep, pigs, cows, You may mix | blend with therapeutic agents or feed, such as horses, cats, dogs, monkeys, chimpanzees, etc. mammals, birds, amphibians, reptiles. As feed, for example, livestock feed used for sheep, pigs, cattle, horses, chickens, etc., feed for small animals used for rabbits, rats, mice, etc., feed for seafood used for eel, Thailand, yellowtail, shrimp, etc., dogs, The pet food used for a cat, a small bird, a squirrel, etc. is mentioned.

  EXAMPLES Next, although this invention is demonstrated in detail based on an Example, this invention is not limited only to this Example.

(Example 1: Production, isolation and purification of resveratrol derivative UHA4003)
700 mg of trans-resveratrol (manufactured by Tokyo Chemical Industry Co., Ltd.) was dissolved in 14 mL of ethanol, and 14 mL of 2.5% aqueous sodium hydrogen carbonate solution was added to obtain a resveratrol-containing solution (pH 9.9). This resveratrol-containing solution was heated at 130 ° C. for 20 minutes in an autoclave (manufactured by Sanyo Electric, “SANYO LABO AUTOCLAVE”, the same applies hereinafter). Subsequently, 14 mL of ethanol and 14 mL of 5.0% aqueous sodium hydrogen carbonate solution were added to the reaction solution obtained by the first autoclave treatment, and the mixture was again heated at 130 ° C. for 20 minutes in the autoclave. When the obtained reaction solution was analyzed by HPLC, compounds represented by several peaks could be confirmed.

The HPLC was performed under the following conditions.
Column: Column for reverse phase “Develosil (registered trademark) C-30-UG-5” (4.6 mm.d. × 250 mm)
Mobile phase: A: H ₂ O (0.1% trifluoroacetic acid (TFA)), B: Acetonitrile (0.1% TFA)
Flow rate: 1 mL / min
Injection: 10 μL
Detection: 254 nm
Gradient (% by volume): 30 minutes from 80% A / 20% B to 20% A / 80% B, 5 minutes from 20% A / 80% B to 100% B, 10 minutes at 100% B (all linear)

  Next, a plurality of peak compounds were collected, and the purity and structure were confirmed by HPLC, high resolution FAB-MS (Fast Atom Bombardment-Mass Spectrometry), and nuclear magnetic resonance measurement, and the elution time was around 16 minutes under the above HPLC analysis conditions. The resveratrol derivative (henceforth UHA4003) shown by said Formula (1) was obtained from the peak seen by this.

(Example 2: Production, isolation and purification of resveratrol derivative UHA1125)
100 mg of trans-resveratrol and 100 mg of ferulic acid (manufactured by Wako Pure Chemical Industries, Ltd.) are dissolved in 2 mL of ethanol, 2 mL of mineral water (trade name “Gerol Steiner” manufactured by Sapporo Beverage Co., Ltd.) is added, and resveratrol is added. A ferulic acid-containing solution (pH: 4.8) was prepared. This resveratrol and ferulic acid-containing solution was heated in an autoclave at 130 ° C. for 30 minutes. When the obtained reaction solution was analyzed by HPLC, compounds indicated by several peaks were confirmed, and these peak compounds were fractionated and analyzed by HPLC, high-resolution electron ionization mass spectrometry (Electron Ionization-Mass Spectrometry). When the purity and structure were confirmed by nuclear magnetic resonance measurement, the resveratrol derivative represented by the above formula (2) (hereinafter referred to as the formula (2)) was observed from the peak observed at around 15.6 minutes under the HPLC analysis conditions described in Example 1. UHA1125) was obtained.

(Example 3: Examination of anti-inflammatory action of resveratrol derivative)
5% of THP-1 cells (derived from human monocytic leukemia cells) in RPMI 1640 medium (Sigma) containing 10% fetal bovine serum (FBS) and phorbol ester (PMA) (Sigma) 0.1 μM CO _2, 37 ° C., and cultured for 24 hours to induce differentiation into monocyte-macrophages. After differentiation induction, resveratrol, ferulic acid, and various resveratrol derivatives obtained in Examples 1 and 2 were added to 0.37 to 30 μM, and lipopolysaccharide (Lipopolysaccharide: LPS, Alexis). Was added at a final concentration of 100 ng / mL and cultured for 48 hours.
Human tumor necrosis factor α (hTNF-α) in the culture supernatant was measured by ELISA (Enzyme Linked Immunosorbent Assay) and compared.

The ELISA was performed using a maxisorp immunoplate (96 well type, manufactured by NUNC). PBS (-) buffer (composition: sodium chloride 137 mM, disodium hydrogen phosphate 8.1 mM, potassium chloride 2.7 mM, potassium dihydrogen phosphate so that the anti-human TNF-α antibody (abcam) is 5 μg / mL. 1.5 mM), and 50 μL each was applied to each well. After allowing to stand at 4 ° C. overnight, each well was washed with PBS (−) buffer in 400 μL × 3 times, and 300 μL of PBS (−) buffer containing 20% immunoblock was applied to each well. After allowing to stand at 25 ° C. for 2 hours, each well was washed with 400 μL × 3 times with PBS (−) buffer, and 50 μL of each culture supernatant was applied to each well. After allowing to stand at 4 ° C. for 1 hour, each well was washed with 400 μL × 3 times with PBS (−) buffer, and anti-human TNF-α antibody (abcam) was added to PBS (− to 0.5 μg / mL. ) /0.1% bovine serum albumin (BSA) and applied to each well. After standing at 25 ° C. for 1 hour, each well was washed with PBS (−) buffer in 400 μL × 3 times, and an anti-Rabbit IgG antibody (HRP labeled) was diluted with PBS (−) / 0.1% BSA in an appropriate amount. 50 μL each was applied to each well. After standing at room temperature for 1 hour, each well was washed with 400 μL × 5 times with PBS (−) buffer, and 3,3 ′, 5,5′-tetramethylbenzidine (TMB) peroxidase-enzyme immunoassay ( 50 μL of EIA) -substrate-kit reagent (Bio-rad) was applied to each well. After an appropriate reaction time, 25 μL of 0.5 M sulfuric acid was applied to each well to stop the reaction. Finally, detection was performed at 450 nm, and the amount of TNF-α production was compared. Based on the relationship between the TNF-α production inhibition rate calculated based on the data obtained from these and the concentration of each compound, the concentration IC ₅₀ (50% inhibition concentration: half maximum inhibitory concentration) that inhibits the production of TNF-α by 50% was calculated. Calculated (Table 1).

  As a result, it was found that the amount of TNF-α produced when each resveratrol derivative (UHA4003, UHA1125) was added was significantly suppressed compared to when resveratrol and ferulic acid were added. It was shown to be prominent as an active ingredient of inflammatory agents.

Examples of resveratrol derivative-containing extracts, foods containing the contained extract, resveratrol derivative-containing pharmaceuticals, resveratrol derivative-containing quasi-drugs, and resveratrol derivative-containing cosmetics are shown below. An example of blending UHA4003 obtained is described, but it goes without saying that UHA1125 can be used as well.
As resveratrol as a raw material, extracts of persimmon fruits and seeds and peanut peels, and as ferulic acid, ferulic acid or rice bran extract as a food additive may be used, but UHA4003 or UHA1125 may be generated. Therefore, it is not limited to these.

(Example 4: Preparation of extract containing UHA4003)
Using a column packed with synthetic adsorbent HP-20 (Mitsubishi Chemical Corporation) and using a conventional method of passing and purifying an ethanol aqueous solution with a stepwise increase in ethanol concentration, grape skin extract powder (manufactured by Marine Bio Inc.) ) From 250 g, 20 g resveratrol was obtained.
20 g of the obtained resveratrol was dissolved in 400 mL of ethanol, and 400 mL of a 2.5% aqueous sodium carbonate solution was added to obtain a resveratrol-containing solution (pH 9.9). This resveratrol-containing solution was heated in an autoclave at 130 ° C. for 20 minutes. Subsequently, 400 mL of ethanol and 400 mL of 5.0% NaHCO ₃ aqueous solution were added to the reaction solution obtained by the first autoclave treatment, and the mixture was heated again at 130 ° C. for 20 minutes in the autoclave. The reaction solution finally obtained is heated to dryness under reduced pressure, and this is heated to reflux with ethanol, and then insoluble matters contained in the obtained reaction mixture are removed by filtration, and then the filtrate is heated under reduced pressure. To give 15 g of a solid. When confirmed by the same method as in Example 1, the obtained solid contained 0.9 g of UHA4003. This work was repeated as necessary.

(Example 5: Food containing UHA4003)
1 g of UHA4003-containing solid material obtained in Example 4 was dissolved in 100 mL of ethanol in advance, and from this, paratinit 500 g (manufactured by Paratinit), reduced maltose starch syrup (manufactured by Towa Kasei Kogyo Co., Ltd., Bx70) 714 g (solid content 500 g) The resulting sugar solution was mixed in a vacuum kettle and cooked to 155 ° C. under a vacuum degree of −600 mmHg. When this was put into a cooling plate and cooled to about 100 ° C., 15 g of citric acid, 1.1 mL of lemon flavor, and 1 mL of pigment were added and solidified after mixing to obtain a non-sugar hard candy. This non-sugar hard candy is easy to eat as a confectionery, and can be used as a functional food that is expected to reduce chronic inflammation and oral inflammation by taking it regularly.

(Example 6: Drug containing UHA4003)
The UHA4003-containing solid material obtained in Example 4 was dissolved in ethanol, added to microcrystalline cellulose and adsorbed, and then dried under reduced pressure. Using this adsorbent, a tableted product was obtained according to a conventional method. The formulation is 10 parts by weight of UHA4003-containing solids, 23 parts by weight of corn starch, 12 parts by weight of lactose, 8 parts by weight of carboxymethyl cellulose, 32 parts by weight of microcrystalline cellulose, 4 parts by weight of polyvinylpyrrolidone, 3 parts by weight of magnesium stearate, talc 8 The weight is as follows. This tableted product can be effectively used as a pharmaceutical for the purpose of healing abnormal production of inflammatory cytokines.

(Example 7: Quasi-drug containing UHA4003)
1.2 g of UHA4003-containing solid material obtained in Example 4 was dissolved in 10 mL of ethanol, and 20 g of taurine, 0.12 g of vitamin B1 nitrate, 0.6 g of sodium benzoate, 4 g of citric acid and 10 g of polyvinylpyrrolidone were dissolved therein. After mixing purified water, it was made up to 1000 mL with purified water. The pH was adjusted to 3.2 using dilute hydrochloric acid. 50 ml of 1000 ml of the obtained solution was filled in a glass bottle and sterilized by heating at 80 ° C. for 30 minutes to complete a quasi-drug drink. This drink can be effectively used as a quasi drug for the purpose of healing abnormal production of inflammatory cytokines in addition to the purpose of nutritional supplementation.

(Example 8: Cosmetics containing UHA4003)
1 part by weight of polyoxyethylene sorbit tetraoleate, 0.5 part by weight of polyoxyethylene stearyl ether, 1 part by weight of glyceryl monostearate, 0.5 part by weight of pyruvic acid, 0.5 part by weight of stearyl alcohol, avocado 1 part by weight of oil and 0.1 part by weight of the UHA4003-containing solid material obtained in Example 4 were mixed and dissolved according to a conventional method. To this, 1 part by weight of sodium lactate, 5 parts by weight of propylene glycol, 0. 1 part by weight, a very small amount of perfume and 89.3 parts by weight of purified water were added and emulsified with a homogenizer to obtain an emulsion. Since this milky lotion contains UHA4003, it can be effectively used as a medicated cosmetic product having a skin disease treatment or prevention effect for psoriasis and atopic dermatitis.

Claims (2)

Formula (1):

And formula (2):

An anti-inflammatory agent comprising at least one compound selected from the group consisting of a resveratrol derivative represented by formula (I) and a pharmaceutically acceptable salt thereof as an active ingredient.   A food, cosmetic, pharmaceutical product or quasi drug containing the anti-inflammatory agent according to claim 1.