JP2006298800A - Polyphenol having action of fibroblast activation and food supplement and cosmetic containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a polyphenol having little side effects and excellent action of fibroblast activation and to provide an excellent food supplement and an excellent cosmetic each containing a polyphenol and having little side effects. <P>SOLUTION: The polyphenol having action of fibroblast activation contains an epigallocatechin derivative. The derivative is composed of a parent nucleus of a polyphenol and any one of teaflavin, ellagic acid, betaine, ascorbic acid, dehydrokraepellic acid, 6-oxooctadecanoic acid, γ-linolenic acid, linoleic acid, oleic acid, palmitic acid, and stearic acid and bonded through an ester linkage to position 3 of ring A of the parent nucleus. A polyphenol is also provided which is obtained by adding cellulase to a pulverized plant material and extracting the product with liquefied carbon dioxide or hexane. The food supplement and the cosmetic each contains the polyphenol having action of fibroblast activation. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

The present invention relates to a polyphenol having a fibroblast activation action having an anti-inflammatory action and an anti-cancer action, a food preparation containing the same, and a cosmetic.

Fibroblasts are activated in the process of repairing wounds and inflammation, repairing wounds early. In addition, the growth of cancer is stimulated by a decrease in extracellular matrix, and further, it grows in the form of dissemination and metastasis to multiple organs. Furthermore, in the dermal tissue of the skin, fibroblasts produce an extracellular matrix that maintains skin elasticity, such as collagen and fibronectin. The factor that activates fibroblasts has already been studied and searched in the pharmaceutical, cosmetic and food industries (see, for example, Non-Patent Document 1).

Among chemical agents that activate fibroblasts, chemically synthesized preparations are concerned about side effects on the digestive organs, lungs, kidneys, and blood (see, for example, Non-Patent Document 2). Furthermore, since there is a high possibility of resistance to the body, it cannot be used for a long time (see, for example, Non-Patent Document 3). On the other hand, a substance having a fibroblast activation action derived from a natural product has advantages that it has few side effects and can be used for a long time, but its absorption and stability are poor and its action is slight. Disadvantages are observed.

Although catechins derived from green tea and resveratrol contained in red grapes are known as substances having a fibroblast activation action derived from natural products, their action is mild and water-soluble, so poor absorption Is unstable. In addition, although catechins have been found in the leaves and stems of oysters of the cypress family and cypresses of the cypress family, their action and structure have not been investigated.

There are few examples of invention about the polyphenol which activates a fibroblast, and various polyphenol derivatives are only known as a manufacturing method of a flavonoid compound (for example, refer patent document 1). Moreover, although anti-inflammatory action by catechins has been reported as a method for producing tea leaf saponins and a drug containing tea leaf saponins, structural identification of useful substances has not been achieved (for example, see Patent Document 2). Furthermore, although a substance containing polyphenol or catechin has been reported as a composition suitable for an external preparation, it has not been identified as a substance and remains in the composition (see, for example, Patent Document 3).
JP 2001-247594 A JP-A-7-61993 JP-A-10-114670 Imitola J et al., Proc. Natl. Acad. Sci. USA, 101, 18117-22, 2004. Scott Am et al., Clin. Cancer Res, 9, 1639-47, 2003. Mihara J et al., Infect. Immun, 61, 3562-4, 1993.

As described above, a chemically synthesized substance having a fibroblast activation action has a side effect of adversely affecting the digestive organs, lungs, kidneys and blood. In addition, chemically synthesized substances have a problem that drug resistance tends to occur.

However, there is a problem that natural substances are not easily absorbed, are unstable, and have a mild effect. Therefore, there is a demand for a substance derived from a natural product having weak side effects and a stable and excellent fibroblast activation action.

The present invention has been made paying attention to the problems existing in the prior art as described above. The object is to provide a polyphenol having weak side effects and having an excellent fibroblast activation action. Another object of the present invention is to provide an excellent food preparation and cosmetics containing polyphenols having weak side effects and good fibroblast activation action.

In order to achieve the above object, the invention according to claim 1 relates to a polyphenol having a fibroblast activation action represented by the following formula (1).

Ｘは、テアフラビン酸、エラグ酸、ベタイン、アスコルビン酸、デヒドロクレペリン酸、６−オキソオクタデカノイン酸、γ−リノレン酸、リノール酸、オレイン酸、パルミチン酸、ステアリン酸のうち、いずれかが、母核のＡ環の３位にエステル結合したもの。
Ｙは、水酸基又はメトキシ基である。

X is theaflavic acid, ellagic acid, betaine, ascorbic acid, dehydrocreperic acid, 6-oxooctadecanoic acid, γ-linolenic acid, linoleic acid, oleic acid, palmitic acid, stearic acid, An ester bond at the 3-position of the A ring of the nucleus.
Y is a hydroxyl group or a methoxy group.

In the invention according to claim 2, cellulase is added to the leaves, stems or ground pulverized products of the camellia plant, cypress plant or cypress plant, or the barley young leaf is heated, and then liquefied carbon dioxide or hexane is added. The polyphenol having an action of activating fibroblasts according to claim 1, which is obtained by adding and mixing, filtering to collect a filtrate, and removing liquefied carbon dioxide or hexane.

Invention of Claim 3 is related with the foodstuff formulation containing the polyphenol which has the fibroblast activation effect | action of Claim 1 or Claim 2.

Invention of Claim 4 is related with the cosmetics containing the polyphenol which has the fibroblast activation effect | action of Claim 1 or Claim 2.

Since this invention is comprised as mentioned above, there exist the following effects.
According to the polyphenol having the fibroblast activation action according to claim 1, the side effect is weak and an excellent anti-inflammatory action is exhibited.

According to the polyphenol having the fibroblast activation action according to claim 2, the polyphenol has a weak side effect and exhibits an excellent anti-inflammatory action.

According to the food preparation of claim 3, it is possible to obtain a food preparation that exhibits weak side effects and exhibits an excellent anti-inflammatory action.

According to the cosmetic of claim 4, it is possible to obtain a cosmetic that has weak side effects and exhibits an excellent anti-inflammatory effect.

Hereinafter, embodiments embodying the present invention will be described in detail.

First, the polyphenol having a fibroblast activation effect of the present embodiment is represented by the following formula (1).

Ｘは、テアフラビン酸、エラグ酸、ベタイン、アスコルビン酸、デヒドロクレペリン酸、６−オキソオクタデカノイン酸、γ−リノレン酸、リノール酸、オレイン酸、パルミチン酸、ステアリン酸のうち、いずれかが、母核のＡ環の３位にエステル結合したもの。
Ｙは、水酸基又はメトキシ基である。

X is theaflavic acid, ellagic acid, betaine, ascorbic acid, dehydrocreperic acid, 6-oxooctadecanoic acid, γ-linolenic acid, linoleic acid, oleic acid, palmitic acid, stearic acid, An ester bond at the 3-position of the A ring of the nucleus.
Y is a hydroxyl group or a methoxy group.

The basic skeleton is polyphenol, particularly flavanones, epicatechin derivatives, and epigallocatechin derivatives or epigallocatechin methoxy derivatives. The optical rotation is negative. X which is the hydroxyl group at the 3-position of the C ring has an ester bond.

The polyphenols shown here, especially epigallocatechin derivatives, enter the cells that cause inflammation and act on transcription factors that produce inflammatory cytokines. At the same time, they bind to the cell membrane of fibroblasts, and transmit cyclic AMP. To promote the synthesis of proteins such as collagen, elastin and fipronectin, and to activate fibroblasts. Produced collagen, elastin and fibronectin close the wound and improve wound healing.

The epigallocatechin derivatives shown here are more oil-soluble than epigallocatechin and methoxyepigallocatechin, easily penetrate into the fibroblast membrane and absorb easily into the endoplasmic reticulum and nuclear membrane. It has the feature that it has excellent properties.

Since the epigallocatechin derivative is a natural substance and is composed of ester bonds, it is decomposed by esterases in the liver and blood, so it has fewer side effects than synthesized compounds. There are features.

The compound represented by X binds to the 3-position of the C ring of the mother nucleus, and theaflavic acid, ellagic acid, betaine, ascorbic acid, dehydrocreperic acid, 6-oxooctadecanoic acid, γ-linolenic acid, linol Any one of acid, oleic acid, palmitic acid and stearic acid and a hydroxyl group of the mother nucleus are ester-bonded.

The compound represented by Y is bonded to the 5-position, 7-position of the A ring of the mother nucleus, and the 3'-position, 4'-position or 5'-position of the B-ring, and is a hydroxyl group or a methoxy group.

When X is theaflavic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-theaflavyl epigallocatechin or 3-theaflavyl methoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group. This 3-teaflavyl methoxyepigallocatechin has a cyclooxygenase inhibitory action on theaflavic acid, so it can suppress inflammation by different mechanisms, has no side effects, is highly oil-soluble, and is absorbed from the skin and digestive tract. Is also preferable from a good point.

When X is ellagic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-ellag epigallocatechin or 3-ellag methoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group. In this 3-ellag methoxyepigallocatechin, ellagic acid exhibits tyrosinase inhibitory action, suppresses the production of melanin, has no side effects, is highly oil-soluble, and is well absorbed from the skin and digestive tract. This is preferable for the solution.

When X is betaine and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-betile epigallocatechin or 3-betile methoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group. Since 3-betaylmethoxyepigallocatechin has a skin cell stimulating action by betaine, it can protect skin cells from inflammation, improve damage, has high oil solubility, and is well absorbed from the skin and digestive tract. And it is preferable from the point which does not have a side effect.

When X is ascorbic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-ascorbyl epigallocatechin or 3-ascorbyl methoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group. This 3-ascorbyl methoxyepigallocatechin is preferable because it exhibits an antioxidant effect by ascorbic acid, prevents skin oxidative damage, has no side effects, is highly oil-soluble, and is well absorbed from the skin and digestive tract. .

When X is dehydrocreperic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-dehydrocrevelyl epigallocatechin or 3-dehydrocrevelylmethoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group.

When X is 6-oxooctadecanoic acid and Y is a hydroxyl group or a methoxy group, a polyphenol having a fibroblast activation action is 3- (6-oxooctadecanoyl) epigallocatechin or 3- (6- Oxooctadecanoyl) methoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group.

When X is γ-linolenic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-γ-linolel epigallocatechin or 3-γ-linolel methoxyepigallocatechin. . The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group. This 3-γ-linolel epigallocatechin or 3-γ-linolel methoxyepigallocatechin has an inhibitory action on the production of inflammatory cytokines in γ-linolenic acid, and has no side effects, high oil solubility, and skin And is also preferable because of good absorption from the digestive tract.

When X is linoleic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-linol epigallocatechin or 3-linol methoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group.

When X is oleic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-oleylepigallocatechin or 3-oleylmethoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group.

When X is palmitic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-palmitoyl epigallocatechin or 3-palmitoylmethoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group.

When X is stearic acid and Y is a hydroxyl group or a methoxy group, the polyphenol having a fibroblast activation action is 3-stearyl epigallocatechin or 3-stearyl methoxyepigallocatechin. The 5-position, 7-position of the A ring and the 3'-position, 4'-position or 5'-position of the B-ring are a hydroxyl group or a methoxy group.

The polyphenol having a fibroblast activation action is preferably extracted from a natural product, but can also be obtained by chemical synthesis. It can also be obtained by esterification by enzymatic reaction. Furthermore, it can be produced by plant callus culture, yeast culture, cell culture or genetically modified bacteria.

These polyphenols having an action to activate fibroblasts are highly oil-soluble, are taken into the cell membranes of skin cells and fibroblasts, are easily absorbed, and are retained in the cells for a long time. It has the feature that the activation action lasts.

The polyphenol thus obtained is used as an oral preparation or a parenteral preparation as an anti-inflammatory agent for wound healing, and is used by being blended in tablets, capsules, drinks, soaps, toothpastes and the like.

Furthermore, since the polyphenol having the fibroblast activation action suppresses cancer invasion and proliferation by enhancing the extracellular matrix, it is used as an anticancer agent and a cancer metastasis inhibitor.

Examples of oral preparations include tablets, capsules, powders, syrups, and drinks. When mixed with the above-mentioned tablets and capsules, it can be used together with a binder, excipient, swelling agent, lubricant, sweetener, flavoring agent and the like. The tablets can also be coated with shellac or sugar. Moreover, in the case of the said capsule, liquid carriers, such as fats and oils, can be further contained in said material. In the case of the syrup and drink, sweeteners, preservatives, pigments, flavoring agents and the like can be contained.

Examples of parenteral preparations include injections in addition to external preparations such as ointments, creams, and liquids. Vaseline, paraffin, fats and oils, lanolin, macro gold, etc. are used as a base material for external preparations, and can be made into ointments, creams, and the like by ordinary methods. Injections include liquids, and other lyophilization agents. This is used aseptically dissolved in distilled water for injection or physiological saline at the time of use. It is also used as a skin wiping agent and toothpaste as a quasi-drug.

The content of the polyphenol having the fibroblast activation action in these anti-inflammatory agents is preferably 0.1 to 20% by weight, more preferably 1 to 15% by weight, and further more preferably 5 to 10% by weight. preferable. When the content of the polyphenol having the fibroblast activation action is less than 0.1% by weight, the action cannot be sufficiently exhibited because the content is too small. On the other hand, when it exceeds 20% by weight, the content of the component contributing to the stability of the preparation is relatively lowered.

These anti-inflammatory agents can be used in combination with other anti-inflammatory agents. When used in combination with indomethacin, ibuprofen, and glucocorticoid, synergistic effects are obtained by different mechanisms of action.

Next, cellulase is added to the leaves, stems or ground pulverized products of the Camellia plant, cypress plant or cypress plant, or the barley leaves are heated, and then liquefied carbon dioxide is added and mixed, followed by filtration. A polyphenol having a fibroblast activation action obtained by collecting a filtrate and removing liquefied carbon dioxide or hexane will be described.

Polyphenol here is polyphenol which exhibits the structure mentioned above. That is, it has a structure represented by the following formula (1).

Ｘは、テアフラビン酸、エラグ酸、ベタイン、アスコルビン酸、デヒドロクレペリン酸、６−オキソオクタデカノイン酸、γ−リノレン酸、リノール酸、オレイン酸、パルミチン酸、ステアリン酸のうち、いずれかが、母核のＡ環の３位にエステル結合したもの。
Ｙは、水酸基又はメトキシ基である。

X is theaflavic acid, ellagic acid, betaine, ascorbic acid, dehydrocreperic acid, 6-oxooctadecanoic acid, γ-linolenic acid, linoleic acid, oleic acid, palmitic acid, stearic acid, An ester bond at the 3-position of the A ring of the nucleus.
Y is a hydroxyl group or a methoxy group.

The plant used as a raw material is a camellia plant, a cypress plant, a cypress plant or a barley young leaf. As the camellia plant, a camellia camellia tea tree is preferable because of its high polyphenol content, and theaaceae camellia sinensis and theaaceae camellia assamika are more preferable because they are easy to grow.

As the cynoaceae plant, the genus Oysteraceae is the genus Fuyuri, Jiro, Hirakumu Mutsu, Koshu Hyakumoku, Shizomi, Tsuji, Dogami Hachiya, Shinano, Grape, Wax, Old Woman, Himeji , Wax and straw are used. Of these, Fuyu-an, Jiro-an, Hei-Kun-an, Koshu-Homome-an, Yotsugo-an, and Dogami-Haya-an are preferred because of their high polyphenol content.

As the cypress family plants, juniper, juniper, hynes and junids belonging to the genus Juniper are used. Among these, the black rat is preferable because of its high polyphenol content.

The plant part of the raw material used is a leaf, stem or fruit. The site to be used is selected depending on the plant to be used.

Leaves or stems are preferred for tea plants belonging to the camellia family Camellia. Leaves, stems or berries are used in the genus Fuyuri, Jiro, Hiramu Mutsu, Koshu Hyakume, Shizomi, and Dogami Bee. Leaves or berries are used in cypresses belonging to the genus Cypress.

When barley young leaves are used as a raw material, it is preferable because the production process of obtaining the desired polyphenol can be easily performed because the leaves are soft.

The raw material is pulverized by a pulverizer. In view of good extraction efficiency, the particle size of pulverization is preferably 100 μm or less, more preferably 10 μm or less, and most preferably 0.5 μm or less. It is preferable to dry the raw material before pulverization because the pulverization due to moisture is improved.

The pulverized raw material is treated with cellulase. As the cellulase used, Onozuka R-10 and Y-NC manufactured by Yakult Pharmaceutical Co., Ltd., Cellulase A “Amano” 3 and Cellulase T “Amano” 4 manufactured by Amano Enzyme Co., Ltd. are used.

The treatment with cellulase is warmed. The cellulase content is preferably 0.1% to 5% based on the weight of the raw material. The heating temperature is preferably 30 ° C. to 50 ° C., and the heating time is preferably 2 hours to 24 hours.

Liquefied carbon dioxide or hexane is added to the cellulase-treated material, and after mixing, the filtrate is collected by filtration, and the liquefied carbon dioxide or hexane is removed to obtain a polyphenol having a fibroblast activation effect. Here, the liquefied carbon dioxide or hexane used as the solvent is of a grade that can be used for food processing. Mixing of liquefied carbon dioxide is performed in a sealed pressure-resistant tank. The liquefied carbon dioxide and hexane have a property of dissolving the target polyphenol, and after the liquefied carbon dioxide is removed, the polyphenol is collected as a liquid as an oil-soluble substance.

The amount of liquefied carbon dioxide added is preferably 2 to 10 times the weight of the raw material. Mixing of hexane is performed in an explosion-proof sealed tank. Hexane has a property of dissolving an oil-soluble substance, and after volatilizing hexane, polyphenol is collected as an oil-soluble substance as a liquid.

The amount of hexane added is preferably 2 to 20 times the weight of the raw material. The obtained liquid is filtered with diatomaceous earth or filter paper, the filtrate is collected, and polyphenol having a fibroblast activation action is obtained as a liquid.

The liquefied carbon dioxide or hexane used as the solvent is removed. As a removal method, a vacuum distillation apparatus, a vacuum dryer or the like is used. The drying temperature is preferably 20 to 50 ° C., more preferably 30 to 40 ° C. from the viewpoint of the stability of the substance. Moreover, 20-60 degreeC is preferable and the temperature of a vacuum dryer has more preferable 25-40 degreeC. By the above operation, a polyphenol having a fibroblast activation effect is obtained as an oily or powdery substance.

The polyphenol thus obtained is used as an oral or parenteral agent as an anti-inflammatory agent, and as an anti-inflammatory agent, it is used by blending in tablets, capsules, drinks, soaps, toothpastes and the like.

Examples of oral preparations include tablets, capsules, powders, syrups, and drinks. When mixed with the above-mentioned tablets and capsules, it can be used together with a binder, excipient, swelling agent, lubricant, sweetener, flavoring agent and the like. The tablets can also be coated with shellac or sugar. Moreover, in the case of the said capsule, liquid carriers, such as fats and oils, can be further contained in said material. In the case of the syrup and drink, sweeteners, preservatives, pigments, flavoring agents and the like can be contained.

Examples of parenteral preparations include injections in addition to external preparations such as ointments, creams, and liquids. Vaseline, paraffin, fats and oils, lanolin, macro gold, etc. are used as a base material for external preparations, and can be made into ointments, creams, and the like by ordinary methods. Injections include liquids, and other lyophilization agents. This is used aseptically dissolved in distilled water for injection or physiological saline at the time of use. It is also used as a skin wiping agent and toothpaste as a quasi-drug.

The content of the polyphenol having the fibroblast activation action in these anti-inflammatory agents is preferably 0.1 to 20% by weight, more preferably 1 to 15% by weight, and further more preferably 5 to 10% by weight. preferable. When the content of the polyphenol having the fibroblast activation action is less than 0.1% by weight, the action cannot be sufficiently exhibited because the content is too small. On the other hand, when it exceeds 20% by weight, the content of the component contributing to the stability of the preparation is relatively lowered.

These anti-inflammatory agents can be used in combination with other anti-inflammatory agents. When used in combination with indomethacin, ibuprofen, and glucocorticoid, synergistic effects are obtained by different mechanisms of action.

Next, a food preparation containing a polyphenol having a fibroblast activation effect will be described. The food preparation here is used as a feed for animals, a feed for pets, or a supplement in addition to general foods and health foods taken by humans.

This food preparation contains the polyphenol having the fibroblast activation action as an active ingredient. The proportion of the polyphenol in the food preparation is 0.1 to 30% by weight, preferably 0.3 to 20% by weight, and more preferably 0.5 to 15% by weight.

When this ratio is less than 0.1% by weight, there is a possibility that sufficient action is not exhibited. Moreover, when this ratio exceeds 30 weight%, there exists a possibility that a form cannot be maintained as a food formulation.
In that case, by adding to various food materials or beverage materials, it is possible to obtain food preparations in the form of powder, tablets, liquids (drinks, etc.), capsules, and the like. Moreover, you may add a base material, an excipient | filler, an additive, a subsidiary material, a bulking agent, etc. suitably.

The food preparation is taken orally in several divided doses per day. The daily intake is preferably 0.1 to 10 g, more preferably 0.3 to 5 g, and even more preferably 0.5 to 3 g. If the daily intake is less than 0.1 g, sufficient effects may not be exhibited. If the daily intake exceeds 10 g, the cost may increase. In addition to the above, it can be used in the form of rice cake, rice crackers, cookies, beverages, powders and the like.

Since this polyphenol is bound to a fatty acid or the like, this food preparation is excellent in absorbability from the gastrointestinal tract and, when absorbed, has a feature that it binds to the cell membrane and has high durability. In addition, it is highly safe because it is decomposed by enzymes in the body.

The obtained food preparation is preferably used as a nutritional functional product or a food for specified health use as a health functional food.

When the obtained food preparation is used for pets, it has a deodorizing action due to polyphenols, which is preferable for faecal measures for animals kept in the home. Since the polyphenol has a function of suppressing inflammation and recovering wounds, the obtained food preparation has a function of recovering inflammation such as stomatitis and gastritis.

Next, the cosmetics containing the polyphenol which has the fibroblast activation effect | action mentioned above are demonstrated. The cosmetics referred to here are those used for pets and animals to improve their forms in addition to cosmetics used for humans. This cosmetic suppresses skin inflammation and is also used for wound healing.

It can be used together with surfactants, solvents, thickeners, excipients and the like according to conventional methods as cosmetics. For example, it can be in the form of oil-soluble cream, hair gel, facial cleanser, cosmetic liquid, lotion and the like. The form of the cosmetic is arbitrary, and can be used as a solution, cream, paste, gel, gel, solid or powder.

As a cosmetic, it is applied, wiped or sprayed several times a day. The daily usage is preferably from 0.01 to 5 g, more preferably from 0.05 to 3 g, even more preferably from 0.1 to 1 g. If the daily usage is less than 0.01 g, sufficient effects may not be exhibited. If the daily usage exceeds 5 g, the cost may increase.

The obtained cosmetic product activates fibroblasts in the dermis of the skin, and is therefore used as a cosmetic product that retroactively improves elasticity. It is also used as a quasi drug.

Hereinafter, the embodiment will be specifically described with reference to examples and test examples.

2 kg of young leaves of Tominyu from Japan were dried with a dryer for 12 hours, and pulverized to a particle size of 0.7 μm with a pulverizer (Sanpoku Universal Crusher). 18 g of cellulase (Y-NC) manufactured by Yakult Pharmaceutical Co., Ltd. was added to 1.8 kg of the pulverized product and stirred at 25 ° C. for 12 hours. The obtained pulverized product was transferred to a supercritical extraction system (JASCO, JASCO SCF201), and 10 L of liquefied carbon dioxide solution was added. This was extracted for 6 hours and dried under reduced pressure to obtain a green liquid. This liquid was dried with a vacuum dryer to obtain 850 g of polyphenol having a fibroblast activation action as a green oily substance. This oily substance was analyzed by a high performance liquid chromatography equipped with a mass spectrometer (HPLC, Shimadzu Corporation), and analyzed by a nuclear magnetic resonance apparatus (NMR, manufactured by Bruker, AC-250). As a result, 3-teaflavin-5,7,3 ′ , 4′-methoxyepigallocatechin, 3-ellag-5,7-methoxyepigallocatechin, 3-betile-3 ′, 4 ′, 5′-methoxyepigallocatechin, 3-ascorbyl-5,7-methoxyepi Gallocatechin, 3-γ-linolel epigallocatechin, 3-palmitoyl epigallocatechin and 3-stearyl epigallocatechin are 5.1, 4.6, 3.3, 0.7, 2.2, respectively. 1.5 and 1.9% by weight were contained.

1 kg of Japanese cypress family juniper sprouts was dried for 12 hours with a dryer and pulverized to a particle size of 0.9 μm with a pulverizer (manufactured by Sanriki Seisakusho Co., Ltd.). 8 g of cellulase (Y-NC) manufactured by Yakult Pharmaceutical Co., Ltd. was added to 0.8 kg of the pulverized product and stirred at 29 ° C. for 10 hours. The obtained pulverized product was transferred to a stainless steel tank (manufactured by Sanwa Sangyo Co., Ltd.), and 8 L of hexane was added. This was extracted for 3 hours, and dried under reduced pressure to remove hexane to obtain a brown liquid. This liquid was dried with a vacuum dryer to obtain 330 g of polyphenol having a fibroblast activation action as a brown oily substance. This oily substance was analyzed by high performance liquid chromatography with a mass spectrometer (HPLC, Shimadzu Corporation) and analyzed by NMR. As a result, 3-theaflavyl-5,7,4 ′, 5′-methoxyepigallocatechin, 3-ellagepi Gallocatechin, 3-bethylepigallocatechin, 3-ascorbyl-3 ′, 4 ′, 5′-methoxyepigallocatechin, 3-γ-linolel-5,7,3 ′, 4 ′, 5′-epigallo Catechin, 3-oleyl-5,7,3 ′, 4 ′, 5′-methoxyepigallocatechin, 3-palmitoyl-5,3 ′, 4′-methoxyepigallocatechin and 3-stearyl-5,7,3 '-Methoxyepigallocatechin was contained at 6.3, 3.9, 2.9, 0.4, 1.2, 2.1, 1.8 and 1.3% by weight, respectively.

Hereinafter, experiments using human skin-derived fibroblasts will be described. This is a test method for evaluating the activation effect by using fibroblasts derived from human skin.
(Test Example 1)

Normal human adult dermal fibroblasts (Fibrocell NHDF (AD), manufactured by Kurabo Corp.) were cultured in a dedicated culture solution, and each of the polyphenols having a fibroblast activation action obtained in Example 1 and Example 2 was obtained. 0.1 mg, 0.3 mg and 1 mg were added and cultured at 37 ° C. for 48 hours. The number of cell growth relative to the solvent control was counted, and the amount of collagen was further observed by the antibody method (manufactured by Chondrex).

As a result, the growth rates of 0.1 mg, 0.3 mg, and 1 mg of the polyphenol of Example 1 were 121%, 230%, and 451%, respectively, and significant growth was recognized as compared with the control group. Furthermore, the growth rates of 0.1 mg, 0.3 mg, and 1 mg of the polyphenol of Example 2 were 113%, 245%, and 390%, respectively, and significant growth was recognized as compared with the control group. In addition, the amount of collagen in each of the samples of Example 1 and Example 2 was significantly increased. Therefore, the polyphenols of Example 1 and Example 2 both exhibited a fibroblast activation effect.

Below, the Example of the anti-inflammatory agent which uses the polyphenol which has a fibroblast activation effect | action as an active ingredient is demonstrated.

1 g of polyethylene glycol monostearate and 1 g of lipophilic glyceryl monostearate were dissolved in ethanol. To the obtained solution, 0.2 g of each of the polyphenols having the fibroblast activation action obtained in Example 1 and Example 2 was added. These were dissolved and then cooled to obtain an anti-inflammatory agent. As a control, a base material containing no polyphenol obtained in Example 1 and Example 2 was prepared.

Below, the Example of the foodstuff formulation containing the polyphenol which has a fibroblast activation effect | action is demonstrated.

0.2 g of polyphenol having an action of activating fibroblasts obtained in Example 1, 0.2 g of propolis extract, 3 g of isomerized sugar, 1.8 g of edible cellulose, 0.01 g of ascorbic acid and 0.1 g of edible flavor Mixed in ratio. This was tableted by a conventional method to obtain a triangular tablet having a diameter of 10 mm and a weight of 0.3 g.

Below, the Example of the cosmetics containing the polyphenol which has a fibroblast activation effect | action is demonstrated.

Polyethylene glycol monostearate, 1 g of lipophilic glyceryl monostearate, 2 g of horse oil ester and 3 g of oleic acid were heated and dissolved. To the obtained solution were added 0.2 g of polyphenol having the fibroblast activation effect obtained in Example 2, 2 g of propylene glycol, 0.1 g of dipotassium glycyrrhizinate, 0.1 g of α-tocopherol and 70 g of purified water. . These were dissolved and then cooled to obtain an emulsion.

The effects and side effects of anti-inflammatory agents, food preparations and cosmetics against inflammation caused by sunburn were evaluated below.
(Test Example 2)

Six healthy men were irradiated with ultraviolet rays on the back skin for 1 hour with a suntanning machine (HAPRO LUXURA Delta 500) to create a mild sunburn on the back. Of these, 1 g of the anti-inflammatory agent obtained in Example 3 and 1 g of the cosmetic obtained in Example 5 were soaked in gauze and applied to the backs of three people. A control was also applied at the same time.

In addition, three people tanned on the other back took 3 tablets of the food preparation obtained in Example 4 after each morning and night meal. 24 hours after application or ingestion of food preparation, urine is collected to measure 8-hydroxy-2'-deoxyguanosine (8OHdG), which is an index of oxidative damage (high-sensitivity 8-OHdG Check, Japan Institute of Aging Control) The absorbance at 450 nm was measured with a microplate reader (manufactured by Bio-Rad), and the 8OHdG amount was determined from the conversion formula.

As a result, the amount of 8OHdG was 68% on average when the anti-inflammatory agent of Example 3 was applied when the control group was 100%, and 61% on average when the anti-inflammatory agent of Example 3 was applied. In the case of the intake of Example 4, the average value was 89%, and when the cosmetic product of Example 5 was applied, the average value was 77%. In all cases, the values were statistically significantly reduced, and an anti-inflammatory effect was confirmed.

On the other hand, no abnormalities were found in any of the test items in the results of simultaneous application site and whole body diagnosis, blood test, blood biochemical test, and the use of Example 3, Example 4 and Example 5 No side effects were observed.

In addition, the said embodiment can also be changed and comprised as follows.
-You may biochemically synthesize | combine the polyphenol which has the fibroblast activation effect | action shown by said Formula (1). That is, by using a fatty acid such as epigallocatechin and γ-linolenic acid, ascorbic acid, betaine, ellagic acid or the like as a raw material and reacting with lipase, a desired polyphenol having a fibroblast activation effect can be obtained. .

Next, the technical idea that can be grasped from the embodiment will be described below.
The polyphenol having a fibroblast activating action according to claim 1, wherein the polyphenol having a fibroblast activating action represented by the formula (1) is 3-γ-linolel methoxyepigallocatechin. When constituted in this way, side effects are weak and an excellent anti-inflammatory effect can be exhibited.

Since the polyphenol having an excellent fibroblast activation action with a weak natural side effect obtained in the present invention has a function of suppressing the growth of cancer cells in addition to a function of exhibiting an anti-inflammatory action, The utility value is high. The target food preparation is expected to improve the environment in the oral cavity and suppress inflammation of the gastrointestinal tract and promote health widely. In addition, by activating skin fibroblasts, the elasticity of the skin is improved by collagen and fibronectin, and new retrospective applications and applications as cosmetics are also expected. In addition, since polyphenols bonded to fatty acids are excellent in absorption and sustainability, the frequency of eating or application is reduced, and the user's QOL can be improved.

Claims (4)

The polyphenol which has the fibroblast activation effect | action shown by following formula (1).

X is theaflavic acid, ellagic acid, betaine, ascorbic acid, dehydrocreperic acid, 6-oxooctadecanoic acid, γ-linolenic acid, linoleic acid, oleic acid, palmitic acid, stearic acid, An ester bond at the 3-position of the A ring of the nucleus.
Y is a hydroxyl group or a methoxy group. Cellulase is added to the leaves, stems or crushed fruits of camellia plant, cypress plant or cypress plant, or young barley leaves are heated, mixed with liquefied carbon dioxide or hexane, filtered. The polyphenol which has a fibroblast activation effect | action of Claim 1 obtained by extract | collecting a filtrate and removing liquefied carbon dioxide or hexane. The food formulation containing the polyphenol which has a fibroblast activation effect | action of Claim 1 or Claim 2. Cosmetics containing the polyphenol which has a fibroblast activation effect | action of Claim 1 or Claim 2.