JP2008169174A - Bergenin derivative having inflammatory cytokine production-inhibiting action, food preparation, cosmetic, antiinflammatory agent comprising the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a bergenin derivative which is weak in side effects and has an excellent inflammatory cytokine production-inhibiting action, and to provide a food preparation, a cosmetic, and an inflammatory agent comprising the same. <P>SOLUTION: This bergenin derivative having the inflammatory cytokine production-inhibiting action is a derivative obtained by binding bergenin to either of palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid, and is obtained by adding lipase for transesterification to the ground product of Saxifraga stolonifera or Mallotus japonicus leaves or flowers, heating the mixture and then extracting the product with a vegetable oil, or fermenting fishes and soybeans with Bacillus natto and then extracting the fermentation product with a vegetable oil. The food preparation or cosmetic comprises the bergenin derivative, a Chrysanthemum morifolium flower extract-containing vegetable oil, and a pine leaf extract-containing vegetable oil. The inflammatory agent comprises the bergenin derivative. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

The present invention relates to a bergenin derivative having an inhibitory action on inflammatory cytokine production. The present invention also relates to food preparations, cosmetics and anti-inflammatory agents comprising the above-mentioned bergenin derivative, chrysanthemum flower extract-containing vegetable oil, and pine needle extract-containing vegetable oil.

Inflammatory cytokines are several proteins produced by inflammatory cells such as macrophages, lymphocytes and monocytes during inflammation.

Inflammatory cytokines also induce inflammatory prostaglandins, which damage tissue cells and cause fever, swelling, redness and pain throughout the body.

Inflammatory cytokines include interleukin-1 alpha, interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor alpha (TNFalpha), which are proteins having a molecular weight of about 10,000 to 30,000. It is.

Among these, interleukin-1 alpha and interleukin-1 beta are released from monocytes and lymphocytes, which are inflammatory cells, and promote the secretion of interleukin-6, interleukin-8, and TNFalpha, interleukin- 6 is involved in fever and tissue damage. TNF alpha is also called cachectin, and is released during cachexia of cancer, resulting in worsening of systemic symptoms (see, for example, Non-Patent Document 1).

These inflammatory cytokines are produced by induction in cells due to bacterial or viral infection. The pathway includes a protein kinase C system and an intracellular signal transduction system via calcium. Furthermore, transcription factors kappa B (NF-kappa B) and NF-IL6, which are transcription factors in the nucleus, have been reported to promote transcription of messenger RNA of inflammatory cytokines (see, for example, Non-Patent Document 2).

Steroid hormone preparations exist as substances that suppress the production of inflammatory cytokines. These steroid hormone preparations suppress the protein kinase C system and transcription factors of inflammatory cytokines in inflammatory cells, thereby suppressing the production of inflammatory cytokines. (For example, refer nonpatent literature 3).

However, steroid hormone preparations such as clobetasol propionate, diflorazone acetate, prezonidolone and cortisone have known side effects such as decreased immune function, opportunistic infection, infection, adrenal function, steroid purpura and dermatitis (for example, (Refer nonpatent literature 4.).

As a result, steroid hormone preparations have the disadvantage that they cannot be used in large quantities for long periods.

Licorice and herbs are known as natural anti-inflammatory agents. Licorice contains glycyrrhizic acid, and its function has been reported to have a steroid-like action (see, for example, Non-Patent Document 5). However, its work is mild and has the disadvantage of not lasting.

Naturally derived plant materials are used as pharmaceuticals, foods, cosmetics, etc. Among them, Yukinoshita is the scientific name Saxifraga strononifera, and Akamegasiwa is the scientific name Mallotus japonicus, both of which identify the components involved in anti-inflammatory activity And its action has not been elucidated.

The invention of a substance or anti-inflammatory agent that suppresses the production of inflammatory cytokines relates to an isolated nucleic acid molecule encoding a cytokine-suppressing anti-inflammatory drug binding protein having the amino acid sequence of the drug binding protein or a complementary chain molecule thereof (For example, refer to Patent Document 1).

There is also an invention of a human antibody that binds to human TNF alpha, which relates to an antibody that exerts an inhibitory action against inflammatory cytokines (see, for example, Patent Document 2).

Furthermore, in the invention of the protein complex forming agent, polyphenol is an active ingredient, and there is a protein complex forming agent effective as a gene complex, a cell adhesion inhibitor or an immunotolerant (see, for example, Patent Document 3). ). However, there is no invention related to bergenin that suppresses inflammatory cytokine production.
Japanese Patent No. 3377529 JP-A-5-96 JP 2002-255811 A Hernandez-Rodrigues, J. et al. Rheumatology, 43, 294-301, 2004. Devaraj, S.M. Diabetes, 54, 85-91, 2005. Walsh, G.M. M.M. Et al. Endocrinol, 178, 37-43, 2003. Bruner, C.I. R. Et al., Dermatol. Online J, 9, 2, 2003. Sasaki, H .; Pathology, 70, 229-236, 2002-2003.

Conventionally, there are steroids as substances that suppress inflammatory cytokines, but there are problems such as adrenal hypertrophy and side effects such as infections. In addition, since the action of naturally-occurring substances is mild and often water-soluble substances, there is a problem that the action persistence is low.

In addition, polyphenols, tannins, alkaloids and polyphenols have a problem that their activity is easily lost by various oxidative stresses and oxidants.

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 bergenin derivative having weak side effects and an excellent inflammatory cytokine production inhibitory effect.

In addition, palmitic acid, gallic acid, eicosapentaenoic acid or docosahexaenoic acid and lipase for transesterification are added to the ground leaves or flowers of Yukinoshita or Akamegashiwa, and the side effects obtained by heating and extraction with vegetable oil are weak and excellent. Another object is to provide a bergenin derivative having an inhibitory action on inflammatory cytokine production.

Provided a bergenin derivative with low side effects obtained by extracting with fermented fish, fermented fermented natto with fermented natto, leaf or flower of edible fish, cynosita or akamegasiwa, and having excellent inhibitory action on inflammatory cytokine production There is to do.

Furthermore, a composition containing 0.01 to 0.5 weight of chrysanthemum flower extract-containing vegetable oil and 0.01 to 0.5 weight of pine leaf extract-containing vegetable oil in 1 weight of a bergenin derivative having an inhibitory action on inflammatory cytokine production It is an object to provide an excellent food preparation.

In addition, a composition containing 0.05 to 0.8 weight of chrysanthemum flower extract-containing vegetable oil and 0.05 to 0.8 weight of pine leaf extract-containing vegetable oil in 1 weight of a bergenin derivative having an inhibitory action on inflammatory cytokine production The object is to provide an excellent cosmetic product with weak side effects.

Another object of the present invention is to provide an excellent anti-inflammatory agent having weak side effects comprising a bergenin derivative having an inhibitory action on inflammatory cytokine production.

In order to achieve the above object, the invention described in claim 1 relates to a bergenin derivative represented by the following formula (1) having an inhibitory action on inflammatory cytokine production.

X is either hydrogen or a methyl group.
Y is either hydrogen or a methyl group.
Z is any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid.

The invention according to claim 2 is obtained by adding palmitic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating, extracting with vegetable oil, Bergenin according to claim 1 Among the derivatives, the present invention relates to a bergenin derivative represented by the following formula (2) having an inhibitory action on inflammatory cytokine production, wherein X is a methyl group, Y is hydrogen, and Z is palmitic acid.

The invention according to claim 3 is obtained by adding gallic acid and lipase for transesterification to a ground product of leaves or flowers of Yukinoshita or Akamegashiwa, heating, extracting with vegetable oil, Bergenin according to claim 1 Among the derivatives, the present invention relates to a bergenin derivative represented by the following formula (3) having an inhibitory action on inflammatory cytokine production, wherein X is a methyl group, Y is hydrogen, and Z is gallic acid.

The invention described in claim 4 is obtained by adding eicosapentaenoic acid and lipase for transesterification to a pulverized product of leaves or flowers of Yukinoshita or Akamegashiwa, heating, and extracting with vegetable oil. Among the bergenin derivatives, the present invention relates to a bergenin derivative represented by the following formula (4) having an inhibitory action on inflammatory cytokine production, wherein X is a methyl group, Y is hydrogen, and Z is eicosapentaenoic acid.

The invention according to claim 5 is obtained by adding docosahexaenoic acid and lipase for transesterification to a pulverized product of leaves or flowers of Yukinoshita or Akamegashiwa, heating, extracting with vegetable oil, Bergenin according to claim 1 Among the derivatives, X is a methyl group, Y is hydrogen, and Z is docosahexaenoic acid, which relates to a bergenin derivative represented by the following formula (5) having an inhibitory action on inflammatory cytokine production.

The invention according to claim 6 is an inflammatory cytokine according to claim 1, which is obtained by extracting a fermented product obtained by adding fermented natto to fermented fish, Yukinoshita or Akagashiwashi leaves or flowers and soybeans with a vegetable oil. The present invention relates to a bergenin derivative having a production inhibitory action.

The invention described in claim 7 includes chrysanthemum per 1 weight of the bergenin derivative having an inhibitory action on inflammatory cytokine production according to claim 1, claim 2, claim 3, claim 4, claim 5, or claim 6. It is related with the foodstuff formulation which consists of a composition containing 0.01-0.5 weight of flower extract containing vegetable oil and 0.01-0.5 weight of pine leaf extract containing vegetable oil.

The invention described in claim 8 includes chrysanthemum per 1 weight of the bergenin derivative having an inhibitory action on inflammatory cytokine production according to claim 1, claim 2, claim 3, claim 4, claim 5, or claim 6. It is related with the cosmetics which consist of a composition containing 0.05 to 0.8 weight of vegetable extract containing vegetable oil and 0.05 to 0.8 weight of pine leaf extract containing vegetable oil.

The invention according to claim 9 is an anti-inflammatory agent comprising the bergenin derivative having an inhibitory action on inflammatory cytokine production according to claim 1, claim 2, claim 3, claim 4, claim 5, or claim 6. It is about.

Since this invention is comprised as mentioned above, there exist the following effects.

According to the bergenin derivative having an inflammatory cytokine production inhibitory action according to claim 1, side effects are weak and an excellent anti-inflammatory action is exhibited.

A bergenin derivative having an inhibitory action on inflammatory cytokine production, obtained by adding palmitic acid and lipase for transesterification to a ground leaf or flower pulverized product of Yukinoshita or Akamegasiwa according to claim 2, heating, and extracting with vegetable oil According to this, side effects are weak and an excellent anti-inflammatory effect is exhibited.

A bergenin derivative having an inhibitory action on inflammatory cytokine production, obtained by adding gallic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa according to claim 3, heating, and extracting with vegetable oil According to this, side effects are weak and an excellent anti-inflammatory effect is exhibited.

A bergenin derivative having an inhibitory action on inflammatory cytokine production, obtained by adding eicosapentaenoic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa according to claim 4, followed by heating and extraction with vegetable oil According to, side effects are weak and an excellent anti-inflammatory effect is exhibited.

A bergenin derivative having an inhibitory action on inflammatory cytokine production obtained by adding docosahexaenoic acid and lipase for transesterification to a ground or leafy pulverized product of Yukinoshita or Akamegashiwa according to claim 5, heating, and extracting with vegetable oil According to this, side effects are weak and an excellent anti-inflammatory effect is exhibited.

According to the edible fish according to claim 6, the leaves or flowers of Yukinoshita or Akamegashiwa and the bergenin derivative having an inhibitory action on the production of inflammatory cytokines obtained by extracting the fermented product obtained by adding natto to fermented soybeans with vegetable oil Therefore, side effects are weak and an excellent anti-inflammatory effect is exhibited.

The bergenin derivative having an inhibitory action on the production of inflammatory cytokine according to claim 7 is added to 0.01 to 0.5 weight of chrysanthemum flower extract-containing vegetable oil and 0.01 to 0.5 weight of vegetable oil containing pine needle extract. According to the food preparation comprising the composition to be contained, side effects are weak and an excellent anti-inflammatory action is exhibited.

The bergenin derivative having an inhibitory action on inflammatory cytokine production according to claim 8 is mixed with 0.05 to 0.8 weight of chrysanthemum flower extract-containing vegetable oil and 0.05 to 0.8 weight of pine leaf extract-containing vegetable oil. According to the cosmetic comprising the composition contained, side effects are weak and an excellent wrinkle improving action is exhibited.

According to the anti-inflammatory agent comprising a bergenin derivative having an inhibitory action on inflammatory cytokine production according to claim 9, side effects are weak and an excellent anti-inflammatory action is exhibited.

Hereinafter, the best mode for carrying out the present invention will be described in detail.

First, a bergenin derivative represented by the following formula (1) having an inhibitory action on inflammatory cytokine production will be described.

X is either hydrogen or a methyl group.
Y is either hydrogen or a methyl group.
Z is any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid.

In the first place, bergenin is a tannin compound existing in nature that is biosynthesized by plants and microorganisms, and its safety has been confirmed.

The bergenin derivative here means that, as shown by the formula (1), palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid A derivative in which any one selected from is bound.

In the above-described bergenin derivative, in the formula (1), X is a methyl group, Y is hydrogen, Z is palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma The carboxylic acid of either linolenic acid or stearic acid has an ester bond.

Although the above-mentioned bergenin is widely distributed in the stems and leaves of Yukinoshita or Akamegashiwa, it has the disadvantage that the structure of bergenin is unstable, and the bergenin derivative is preferable because it is structurally stable and excellent in action. .

The above-mentioned bergenin derivative has a fat solubility by binding one of palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid. As a result, the structure of the bergenin derivative is stabilized, and the anti-inflammatory action is more durable than bergenin.

The bergenin derivative suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8 and TNF alpha.

The above-mentioned bergenin derivative passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, and suppresses the expression of protein kinase C, which plays a central role in inflammation signals, thereby inhibiting the production of inflammatory cytokines. Suppress.

The aforementioned bergenin derivative is bonded with any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid, which have high fat-soluble characteristics. Therefore, it is easier to get into the small intestine and skin cell membrane than bergenin, and it is easily absorbed.

When the above-mentioned bergenin derivative is ingested excessively and absorbed, the excess amount is decomposed by esterase in the blood, and bergenin and its constituents palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid , Alpha-lipoic acid, gamma-linolenic acid and stearic acid, and the safety of bergenin and their respective fatty acids has been confirmed. As a result, the bergenin derivative is also highly safe.

Among the above-mentioned bergenin derivatives, when Z in formula (1) is palmitic acid, the medium-chain saturated fatty acid residue of palmitic acid penetrates into the cell membrane, is easily absorbed into the cell, and easily acts on the target protein kinase C. The anti-inflammatory action is preferably enhanced.

Among the above-mentioned bergenin derivatives, when Z in the formula (1) is gallic acid, the polyphenol group of gallic acid exhibits an antioxidative action, and an anti-inflammatory action against oxidative stress is also taken into account, thereby enhancing the antioxidative action. preferable.

Among the above-mentioned bergenin derivatives, when Z in the formula (1) is eicosapentaenoic acid, the unsaturated fatty acid residue of eicosapentaenoic acid exhibits inflammatory prostaglandin production inhibitory action, so that inflammatory prostas arising from arachidonic acid It is preferable because the amount of glandin is reduced and the anti-inflammatory action is enhanced.

Among the above-mentioned bergenin derivatives, when Z in the formula (1) is docosahexaenoic acid, the unsaturated fatty acid residue of docosahexaenoic acid exhibits platelet aggregation inhibition and arterial dilation action, thereby improving blood flow and anti-inflammatory action. Is preferred because it is enhanced.

Among the above-mentioned bergenin derivatives, when Z in formula (1) is docosapentaenoic acid, the unsaturated fatty acid residue of docosapentaenoic acid exerts a capillary vasodilatory action, thereby improving blood flow in the local area of inflammation. The inflammatory substance is excreted and the anti-inflammatory action is enhanced, which is preferable.

Among the above-mentioned bergenin derivatives, when Z in formula (1) is alpha-lipoic acid, the SH group of alpha-lipoic acid exhibits an anti-oxidant action, suppresses tissue damage to oxidative stress, and has an anti-inflammatory action. It is preferable because it is enhanced.

Among the bergenin derivatives, when Z in the formula (1) is gamma-linolenic acid, the unsaturated fatty acid residue of gamma-linolenic acid suppresses the reaction of inflammatory prostaglandins and the anti-inflammatory action is increased. This is preferable.

Among the above-mentioned bergenin derivatives, when Z in the formula (1) is stearic acid, the saturated fatty acid residue of stearic acid penetrates into the cell membrane and is easily absorbed into the cell, easily acting on the target protein kinase C, This is preferable because the inflammatory action is enhanced.

In addition, it is preferable to process, manufacture, and extract a bergenin derivative using the leaves or flowers of Yukinoshita or Akamegashiwa as raw materials because they are easily available and economical.

When this derivative is extracted, supercritical extraction using an organic solvent such as ethanol, hexane, chloroform, benzene, ethyl acetate, or ether or liquefied carbon dioxide gas is used. In particular, the use of ethanol or hydrous ethanol used for edible processing is preferable because the range of use as food is increased.

Furthermore, it is preferable to purify fatty acids used for bergenin derivatives from plants, beans, and edible fish, or to use purified fats and oils.

For example, these fatty acids can be obtained from Fuji Oil, Nissin Oil, Nissui Pharmaceutical, Nissui Fisheries, Toyo Fisheries, and can be synthesized by biosynthesis using a binding enzyme or chemically.

In the case of a chemical synthesis reaction, it is heated together with a metal catalyst such as magnesium or aluminum. These raw materials are put in a reaction vessel and reacted with the organic solvent. It is preferable to obtain this reaction product as a crude product by removing the solvent because the cost required for purification can be reduced. In addition, it is more preferable to extract the produced derivative with vegetable oil because a highly lipophilic derivative can be efficiently obtained.

When a bergenin derivative is obtained from these raw materials by a biochemical enzymatic reaction, an enzyme that causes an ester bond reaction, such as lipase AY “Amano” 30G, lipase G “Amano” 50, lipase F-AP15 manufactured by Amano Enzyme. Neurase F3G and the like are used.

The target bergenin derivative can be obtained by extraction from a natural material or purification. Examples of natural materials include plants such as saxifrage or akamegasiwa, seaweed, mushrooms, food animals, food fish, molluscs, insects, and crustaceans. In particular, the leaves or flowers of Yukinoshita or Akamegashiwa, the heads of edible fish and the heads of eels are characterized by being easy to extract because of their high content.

The produced bergenin derivative is extracted with the organic solvent or vegetable oil. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil Oils used in edible or cosmetic products such as wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil are used In addition, it is more preferable to use a vegetable oil containing a pine leaf extract, a kokushi extract, a green tea extract, a chrysanthemum extract or a bamboo leaf extract because the intended derivative is stably maintained.

Industrially, the heads of edible fish are removed during the processing of edible fish, are discarded as waste, and are not used. Extracting or refining the edible fish head or eel head as a raw material is preferable because it effectively uses waste and reduces the amount of waste.

It is preferable to obtain the above-mentioned bergenin derivative by fermentation using microorganisms or yeasts because it has been confirmed to be safe for food and has abundant food experience. In this case, the microorganisms used are natto, lactic acid bacteria, red yeast rice Bacillus subtilis and yeast include brewer's yeast and alcoholic yeast, and natto bacteria are particularly preferred because of their excellent transesterification.

The fermentation is carried out using a fermentation tank by adding the microorganism or yeast to a fermentation base such as leaves or flowers of Yukinoshita or Akamegashiwa, edible fish, edible fish heads or internal organs, soybeans or milk. After this fermentation, the desired bergenin derivative can be obtained from a mixture of microorganisms or yeast and fermentation broth by extraction with an organic solvent or vegetable oil.

Among these, the leaves, flowers, and stems of Yukinoshita or Akamegasiwa are preferred because they have abundant food experience and can stably supply the target bergenin derivative. Furthermore, when the target bergenin derivative is separated from the fermented product from the fermented product, the organic solvent or vegetable oil is used. In addition, obtaining an oil-soluble portion that is extracted and separated using an organic solvent or vegetable oil containing pine leaf extract, kokushi extract, chrysanthemum extract, the substance is stabilized by excellent antioxidant power, High quality derivatives are preferred because they are separated.

When extracting from plants, Yukinoshita with the scientific name Saxifraga stolonifera, leaves, flowers, roots and stems with the scientific name Malllotus japonicus, and also green tea, Gyoja garlic, onion, garlic, soybeans, Gigigi, licorice, large leaf , Kuzu flower, capsicum, oyster, pear, chestnut, cod, wasabi, bracken, rice, wheat, corn, radish, rape blossom, cherry, pine, aoki, akane, akamegashiwa, akebi, amachazul, amadokoro, aloe, licorice, itadori , Wild boar, Iris japonica, Ukogi, Moray peony, Udo, Ume, Vulture, Ebisu rush, Oren, Psyllium, Okera, Okra, Hypericum, Onamomi, Ominae, Kakidooshi, Calla Lily, Crowfish Shark, Kawaraketsumei, Kawaranadeshiko, Kanaoi, Kakuyomo, Kikuyo, Kisame, Kihada, Kiranso, Kimihiki, Kusaiso, Kuboke, Kudzu, Gardenia, Kohonone, Kobushi, Saikachi, Sabonshura, Saritorisarabetsusui Assembly, Tamshiba, Taranoki, Dandelion, Chigaya, Tsuruganeninjin, Tsuwabuki, Tochinoki, Tochibaninjin, Nanten, Japanese rose, Japanese chickweed, pearl barley, scallops, Hikikoshi, Hishi, Hitotsuba, Biwa, Fuki, Fukujusou, Fuji, Hajimeki Leaves, stems, flowers or roots such as gentian, forsythia, wintersweet, and walnut are preferred because they are easily available.

Among these, Yukinoshita or Akamegasiwa are plants widely distributed in various parts of Japan, from the mainland of China to Southeast Asia. Yukinoshita or Akamegashiwa used here may be any place of production, and those of cultivation areas where the use history of agricultural chemicals is clear are preferred.

The leaves or flowers, flowers, roots and stems of Yukinoshita or Akamegashiwa are preferred because the desired bergenin derivative is extracted.

Furthermore, when extracting the target bergenin derivative from green tea, the leaves, stems, or roots of Japanese green tea, powdered tea, and Chinese assam green tea are preferable because they are easily available. The green tea here is typically the scientific name Camellia sinensis and includes all green tea belonging to the genus Camellia.

In order to separate the target bergenin derivative, it is preferable to use a purification operation such as a separation resin. It is further preferable to extract the produced bergenin derivative with an organic solvent or vegetable oil. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil Oils used in edible or cosmetic products such as wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil are used In addition, it is more preferable to use an organic solvent, vegetable oil, or the like containing a pine leaf extract, a kokushi extract, a green tea extract, or a chrysanthemum extract because the target derivative is stably maintained.

It is preferable to purify the target bergenin derivative from the reaction product or composition from the viewpoint that the intake amount can be reduced when ingested as a highly pure substance. When highly purified, a separation carrier or resin is utilized and purified. As the separation carrier or resin, porous polysaccharide, silicon oxide compound, polyacrylamide, polystyrene, polypropylene, styrene-vinylbenzene copolymer, etc. whose surface is coated as described later are used. Those having a particle size of 0.1 to 300 μm are preferable. The finer the particle size, the higher the accuracy of the separation, but the longer the separation time.

For example, a reverse phase carrier or a resin whose surface is coated with a hydrophobic compound is used for separation of a highly hydrophobic substance. Those coated with a cationic substance are suitable for the separation of anionically charged substances.

Also, those coated with an anionic substance are suitable for separating a cationically charged substance. When a specific antibody is coated, it is used as an affinity carrier or resin for separating only a specific substance.

The affinity carrier or resin is used for specific preparation of an antigen using an antigen-antibody reaction. A dispersible carrier or resin is used for isolation of substances such as silica gel (manufactured by Merck) if there is a difference in the distribution coefficient between the substances and the solvent for separation.

Among these, an adsorbent carrier or resin, a dispersible carrier or resin, a molecular sieve carrier or resin, and an ion exchange carrier or resin are preferable from the viewpoint of reducing production costs. Furthermore, the reverse phase carrier or resin and the dispersible carrier or resin are more preferable because the difference in the distribution coefficient with respect to the separation solvent is large.

When an organic solvent is used as the separation solvent, a carrier or resin having resistance to the organic solvent is used. Moreover, the carrier or resin utilized for pharmaceutical manufacture or food manufacture is preferable.

From these points, Diaion (Mitsubishi Chemical Corporation) and ZAD-2 or ZAD-4 (Rohm and Haas) are used as the adsorptive carrier, and Sephadex LH-20 (Amersham Pharmacia) is used as the molecular sieve carrier. Silica gel as the distribution carrier, IRA-410 (Rohm and Haas) as the ion exchange carrier, and DM1020T (Fuji Silysia) as the reverse phase carrier are more preferable. Of these, Diaion, Sephadex LH-20 and DM1020T are more preferred.

The obtained extract is suspended in a solvent for swelling the carrier for separation or the resin before separation. The amount is preferably 1 to 50 times, more preferably 3 to 20 times the weight of the extract from the viewpoint of separation efficiency. The separation temperature is preferably 4 to 30 ° C., more preferably 10 to 25 ° C. from the viewpoint of the stability of the substance.

As the separation solvent, water or a lower alcohol containing water, a hydrophilic solvent, or a lipophilic solvent is used. As the lower alcohol, methanol, ethanol, propanol and butanol are used, and ethanol used for food is preferable.

When Sephadex LH-20 is used, a lower alcohol is preferable as the separation solvent. When silica gel is used, the separation solvent is preferably chloroform, methanol, acetic acid or a mixture thereof. When Diaion and DM1020T are used, the separation solvent is preferably a lower alcohol such as methanol or ethanol or a mixed solution of lower alcohol and water.

After collecting the separated fraction, it is preferable to remove the solvent by drying or vacuum drying to obtain the target bergenin derivative as a powder or a concentrated liquid because the influence of the solvent can be excluded. The bergenin derivative is obtained as a liquid or a powder. The obtained bergenin derivatives are used as pharmaceuticals, food preparations, cosmetics, hygiene tools, soaked fibers, plastics, clothing, anti-inflammatory agents against inflammation caused by contaminants, and the like.

Examples of pharmaceuticals include skin, systemic or local anti-inflammatory agents, antiallergic agents, hay fever improving agents, antiobesity agents, lipolytic agents, wrinkle removing agents, fatty liver inhibitors, hyperlipidemia improving agents, anti-arteriosclerosis Used for agents. It is also used as a veterinary medicine such as fish and livestock, or an anti-inflammatory agent for pets, and since the material used is naturally derived, it is highly safe and more preferable. Furthermore, since it also exhibits an inhibitory action against the onset of cancer and mutation caused by inflammation, it is used as a carcinogenesis preventive or cancer suppressant.

As the above-mentioned food preparation, anti-inflammatory, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, metabolic syndrome improvement, fatigue recovery, nourishing tonic, maintenance of liver function, etc. Is done. In addition, this food preparation is more preferable because it is naturally derived for pets and for the growth of fish and livestock.

This cosmetic has anti-inflammatory effects by suppressing the production of inflammatory cytokines, and also exhibits vascular dilation and lymphatic dilation of the skin, so wrinkles and sagging caused by inflammation such as sunburn. It is effective for the suppression or prevention of the production. In particular, it exerts anti-inflammatory action against inflammation caused by sunburn, and removes the cause of wrinkles and sagging. In addition, this cosmetic exhibits an excellent therapeutic or preventive action against atopic dermatitis in which a large amount of inflammatory cytokines are produced.

As sanitary tools, it is used for gauze, masks, pollen countermeasure masks, sanitary products for suppressing inflammation, and clothing for atopic patients. It is also used as an indoor air improver that induces inflammation, plastic materials and clothes used in toilets, deodorants, improvers for sick house disease, fibers, and clothes.

Furthermore, it is also used as a mask, filter and fuel additive for protecting against environmental substances causing inflammation, for example, protecting the body from harmful substances such as dioxin, asbestos, PCB, hydrogen sulfide, nitrogen oxides, etc. . In particular, since it exhibits an inhibitory action against smoking and harmful substances contained in tobacco, it is also used in tobacco filters.

Additives added to fuels used in automobiles and factories because the bergenin derivative protects against environmental pollution caused by soot and diesel particles emitted from factories using the protective effect against environmental pollution. It is preferable to protect the human body from contaminants.

Next, among the bergenin derivatives represented by the above formula (1) obtained by adding palmitic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating and extracting with vegetable oil, A bergenin derivative represented by the following formula (2) having an inhibitory action on inflammatory cytokine production, wherein Z is palmitic acid, will be described.

Here, the bergenin derivative is the bergenin derivative described above, and is a derivative in which carboxylic acid of palmitic acid is ester-bonded to bergenin. X is a methyl group, Y is hydrogen, and Z is palmitic acid.

The bergenin derivative suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8 and TNF alpha.

The bergenin derivative passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, moves into the nucleus, and acts on transcription factors such as NF-kappa B and NF-IL6. Suppresses the production of proinflammatory cytokines by suppressing the gene level expression of sex cytokines.

In addition, the above-mentioned bergenin derivative is preferable because a saturated fatty acid residue of palmitic acid penetrates into the cell membrane, is easily absorbed into the cell, easily acts on the target protein kinase C, and enhances the anti-inflammatory effect.

The above-mentioned bergenin derivative is obtained by adding palmitic acid and a transesterification lipase to a pulverized product of leaves or flowers of Yukinoshita or Akamegashiwa, heating, and extracting with vegetable oil.

The plant used is Yukinoshita or Akamegasiwa. These have been used for folk medicine and medicinal dishes for a long time, have abundant dietary experience, and have been confirmed to be safe. Moreover, the leaf or flower of those plants is used.

It is also used as a cosmetic raw material as an extract of Yukinoshita or Akamegashiwa. As used herein, Yukinoshita or Akamegashiwa is used for any of the naturally bred or cultivated Yukinoshita or Akagashiwiwa, such as Japan, Korea, China, Taiwan and other Asian countries, North America, South America, Oceania and Africa. Of these, those made in Japan and China are preferable because the use history of agricultural chemicals can be traced, the quality is stable, and the price is low.

The leaves or flowers of Yukinoshita or Akamegashiwa may be either fresh or dried. Further, it is preferable that the collected leaves or flowers of Yukinoshita or Akamegashiwa are washed with tap water. The leaves or flowers of Yukinoshita or Akamegashiwa are crushed. A pulverizer is used for pulverization. For example, a free mill, super free mill, sample mill, goblin, super clean mill, micros manufactured by Nara Machinery Co., Ltd., a small vacuum dryer manufactured by Toyo Riko as a vacuum dryer, stock A compact decompression heat transfer dryer DPTH-40 manufactured by Matsui Co., Ltd., clean dry VD-7, VD-20 manufactured by AKM Kyushu Technos Co., Ltd., etc. are used.

Palmitic acid used here is obtained from coconut oil, soybean oil, rapeseed oil, cottonseed oil, corn oil, safflower oil, sesame oil, rice oil, sunflower oil, olive oil, etc., such as Ryoshoku, Nisshin Oil and Fuji Oil Co., Ltd. Those extracted and purified from plants such as coconut palm and soybean are preferred because they have few impurities.

The transesterification lipase used here is, for example, a lipozyme or novozyme 435 manufactured by Novozyme, a lipase PL or lipase QLM manufactured by Meisho Sangyo, or a lipase AY “Amano” manufactured by Amano Enzyme. High quality products such as 30G, lipase G “Amano” 50, lipase F-AP15, and neurase F3G are used, and these are preferable because their safety has been confirmed.

To the clean stainless steel cylinder or the like, the above-mentioned pulverized leaves or flowers, palmitic acid and transesterified lipase are added and heated. Here, it is preferable to add tap water as a solvent from the viewpoint of smoothing the reaction.

The palmitic acid is preferably 0.02 to 0.5 weight and the transesterification lipase is preferably 0.0001 to 0.04 weight with respect to 1 weight of the pulverized product of the leaves or flowers of Yukinoshita or Akagasiwa.

As said temperature of heating, 10-40 degreeC is preferable and 12-37 degreeC is more preferable. Further, the heating time is preferably 1 to 48 hours, more preferably 3 to 36 hours.

The heating is preferably performed while stirring, and a rate of 30 to 160 times per minute is preferable.

It is cooled after being warmed. The cooling method is preferably natural cooling or water cooling.

The reactants are separated by vegetable oil. The reactant is soluble in vegetable oil because of its high oil solubility. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil , Wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil and other oils used in edible or cosmetics are used In addition, it is more preferable to use a vegetable oil containing a pine leaf extract, a kokushi extract, a green tea extract, a chrysanthemum extract or a bamboo leaf extract because the intended derivative is stably maintained.

In particular, the above-mentioned pine leaf extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding a vegetable oil to a pulverized product of pine leaves. Can be separated.

The pine leaves used for the pine leaf extract-containing vegetable oil may be any of Japanese, Chinese and Taiwanese.

Pine leaves cultivated without using pesticides are preferred because they can avoid the danger of pesticides.

The vegetable oil to be added is preferably 0.4 to 3 weights with respect to 1 weight of the pulverized product of leaves or flowers.

The separated bergenin derivative is absorbed into the body, and then the excess amount is decomposed by esterase and further metabolized in the liver. Therefore, safety is high and there are few side effects.

Separating and purifying the target bergenin derivative from the reaction product is preferable from the viewpoint of obtaining a highly pure substance. As a purification method, it is preferable to use a purification operation such as an organic solvent for separation or a resin. As the organic solvent, ethanol, hexane, chloroform, benzene, ethyl acetate, ether and the like are used, and among these, ethanol for food processing or hydrous ethanol is more preferable because it is easy to handle.

As the separation carrier or resin, porous polysaccharide, silicon oxide compound, polyacrylamide, polystyrene, polypropylene, styrene-vinylbenzene copolymer, etc., whose surface is coated, are used. It is preferable that the target bergenin derivative is obtained by separation with an appropriate separation solvent, purification, and removal of the solvent.

The bergenin derivative thus obtained is obtained as a liquid or powder. The obtained bergenin derivative is used for pharmaceuticals, food preparations or cosmetics. As pharmaceuticals, they are used as anti-inflammatory agents, anti-obesity agents, lipolytic agents, wrinkle removing agents, fatty liver inhibitors, hyperlipidemia improving agents, anti-arteriosclerotic agents, anti-allergic agents and the like.

The food preparation is used for anti-inflammatory, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, improvement of metabolic syndrome, nutrition tonic, maintenance of liver function, etc. The

This cosmetic product exhibits anti-inflammatory effects by suppressing the production of inflammatory cytokines, and also exhibits vasodilatory effects on the skin and limba tube dilation, so it suppresses wrinkles and sagging caused by inflammation such as sunburn. Or it is effective for prevention of production. In particular, it exerts anti-inflammatory action against inflammation caused by sunburn, and removes the cause of wrinkles and sagging.

Furthermore, this cosmetic exhibits an excellent therapeutic or preventive action against atopic dermatitis in which inflammatory cytokines are produced in large quantities.

Next, among bergenin derivatives represented by the above formula (1) obtained by adding gallic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating and extracting with vegetable oil, A bergenin derivative represented by the following formula (3) having an inhibitory action on inflammatory cytokine production, wherein Z is gallic acid, will be described.

Here, the bergenin derivative is the bergenin derivative described above, and is a derivative in which carboxylic acid of gallic acid is ester-bonded to bergenin. X is a methyl group, Y is hydrogen, and Z is gallic acid.

The bergenin derivative suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8 and TNF alpha. This bergenin derivative passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, moves into the nucleus and acts on transcription factors such as NF-kappa B and NF-IL6, and the transcription factor is inflammatory. Suppresses the gene level expression of cytokines to suppress the production of inflammatory cytokines.

Further, in the above-mentioned bergenin derivative, saturated fatty acid residues of gallic acid penetrate into the cell membrane, are easily absorbed into cells, are easy to work on the target protein kinase C, and are preferably anti-inflammatory.

The bergenin derivative is obtained by adding gallic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating, and extracting with vegetable oil.

The plant used is Yukinoshita or Akamegasiwa. Yukinoshita or Akamegasiwa are grown or grown in Japan, Asia and all over the world. Both have been used for folk medicine and medicinal dishes for a long time, have abundant dietary experience, and have been confirmed to be safe. The leaves or flowers of these plants are used.

It is also used as a cosmetic raw material as an extract of Yukinoshita or Akamegashiwa. As used herein, Yukinoshita or Akamegashiwa is used for any of the naturally bred or cultivated Yukinoshita or Akagashiwiwa, such as Japan, Korea, China, Taiwan and other Asian countries, North America, South America, Oceania and Africa. Of these, those made in Japan and China are preferable because the use history of agricultural chemicals can be traced, the quality is stable, and the price is low.

The leaves or flowers of Yukinoshita or Akamegashiwa may be either fresh or dried.

It is preferable that the collected leaves or flowers of Yukinoshita or Akamegashiwa are washed with tap water.

The leaves or flowers of Yukinoshita or Akamegashiwa are crushed. For pulverization, a pulverizer is used. For example, a free mill, super free mill, sample mill, goblin, super clean mill, micros manufactured by Nara Machinery Co., Ltd. as a pulverizer, and a small vacuum manufactured by Toyo Riko as a vacuum dryer. A dryer, a small vacuum heat transfer type dryer DPTH-40 manufactured by Matsui Co., Ltd., clean dry VD-7, VD-20 manufactured by AKM Kyushu Technos Co., Ltd., etc. are used.

Gallic acid used here is obtained from coconut oil, soybean oil, rapeseed oil, cottonseed oil, corn oil, safflower oil, sesame oil, rice oil, sunflower oil, olive oil, etc., such as Ryoshoku, Nisshin Oil and Fuji Oil Co., Ltd. Those extracted and purified from plants such as palm and soybean are preferred because they have few impurities.

The transesterification lipase used here is, for example, a lipozyme or novozyme 435 manufactured by Novozyme, a lipase PL or lipase QLM manufactured by Meisho Sangyo, or a lipase AY “Amano” manufactured by Amano Enzyme. High quality products such as 30G, lipase G “Amano” 50, lipase F-AP15, and neurase F3G are used, and these are preferable because their safety has been confirmed.

To the clean stainless steel cylinder, the above-mentioned pulverized leaves of Yukinoshita or Akamegashiwa or flowers, gallic acid and lipase for transesterification are added and heated. Here, it is preferable to add tap water as a solvent from the viewpoint of smoothing the reaction.

The weight of gallic acid is preferably 0.01 to 0.7 weight, and the amount of lipase for transesterification is preferably 0.0001 to 0.06 weight with respect to 1 weight of the pulverized product of leaves or flowers of Yukinoshita or Akamegashiwa.

As said temperature of heating, 10-40 degreeC is preferable and 12-28 degreeC is more preferable.

The warming time is preferably 1 to 48 hours, more preferably 2 to 35 hours.

The heating is preferably performed while stirring, and a rate of 10 to 130 times per minute is preferable.

It is cooled after being warmed. The cooling method is preferably natural cooling or water cooling.

The reactants are separated by vegetable oil. The reactant is soluble in vegetable oil because of its high oil solubility. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil Oils used in edible or cosmetic products such as wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil are used In addition, it is more preferable to use a vegetable oil containing a pine leaf extract, a kokushi extract, a green tea extract, a chrysanthemum extract or a bamboo leaf extract because the intended derivative is stably maintained.

In particular, the above-mentioned pine leaf extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding a vegetable oil to a pulverized product of pine leaves. Can be separated.

The pine leaves used for the pine leaf extract-containing vegetable oil may be any of Japanese, Chinese and Taiwanese.

Pine leaves cultivated without using pesticides are preferred because they can avoid the danger of pesticides.

The vegetable oil to be added is preferably 0.3 to 4 weights with respect to 1 weight of the pulverized material of the leaves or flowers of Yukinoshita or Akamegashiwa.

The separated bergenin derivative is absorbed into the body, and then the excess amount is decomposed by esterase and further metabolized in the liver. Therefore, safety is high and there are few side effects.

Separating and purifying the target bergenin derivative from the reaction product is preferable from the viewpoint that the intake can be reduced as a highly pure substance. As a purification method, it is preferable to use a purification operation such as an organic solvent for separation or a resin. As the organic solvent, ethanol, hexane, chloroform, benzene, ethyl acetate, ether and the like are used, and among these, ethanol for food processing or hydrous ethanol is more preferable because it is easy to handle.

As the separation resin, porous polysaccharides, silicon oxide compounds, polyacrylamide, polystyrene, polypropylene, styrene-vinylbenzene copolymers, etc. whose surfaces are coated are used. It is preferable that the target bergenin derivative is obtained by separation with an appropriate separation solvent, purification, and removal of the solvent.

The bergenin derivative thus obtained is obtained as a liquid or powder. The obtained bergenin derivative is used for pharmaceuticals, food preparations or cosmetics. As pharmaceuticals, they are used as anti-inflammatory agents, anti-obesity agents, lipolytic agents, wrinkle removing agents, fatty liver inhibitors, hyperlipidemia improving agents, anti-arteriosclerotic agents, anti-allergic agents and the like.

The food preparation is used for anti-inflammatory, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, improvement of metabolic syndrome, nutrition tonic, maintenance of liver function, etc. The

This cosmetic product exhibits anti-inflammatory effects by suppressing the production of inflammatory cytokines, and also exhibits vasodilatory effects on the skin and limba tube dilation, so it suppresses wrinkles and sagging caused by inflammation such as sunburn. Or it is effective for prevention of production. In particular, it exerts anti-inflammatory action against inflammation caused by sunburn, and removes the cause of wrinkles and sagging.

Furthermore, this cosmetic exhibits an excellent therapeutic or preventive action against atopic dermatitis in which inflammatory cytokines are produced in large quantities.

Next, among the bergenin derivatives represented by the above formula (1) obtained by adding eicosapentaenoic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating and extracting with vegetable oil The bergenin derivative represented by the following formula (4) having an inhibitory action on inflammatory cytokine production, wherein Z is eicosapentaenoic acid, will be described.

Here, the bergenin derivative is the bergenin derivative described above, and is a derivative in which carboxylic acid of eicosapentaenoic acid is ester-bonded to bergenin. X is a methyl group, Y is hydrogen, and Z is eicosapentaenoic acid.

The bergenin derivative suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8 and TNF alpha.

The bergenin derivative passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, moves into the nucleus, and acts on transcription factors such as NF-kappa B and NF-IL6. Suppresses the production of proinflammatory cytokines by suppressing the gene level expression of sex cytokines. Moreover, in the said bergenin derivative, the saturated fatty acid residue of eicosapentaenoic acid permeates into the cell membrane, is easily absorbed into the cell, is easy to work on the target protein kinase C, and is preferred because the anti-inflammatory action is enhanced.

The bergenin derivative is obtained by adding eicosapentaenoic acid and lipase for transesterification to a pulverized product of leaves or flowers of Yukinoshita or Akamegashiwa, heating, and extracting with a vegetable oil containing pine leaf extract.

The plant to be used is Yukinoshita or Akamegashiwa. Yukinoshita or Akamegashiwa are grown or grown in books, Asia, and around the world. Both have been used for folk medicine and medicinal dishes for a long time, have abundant dietary experience, and have been confirmed to be safe. These leaves or flowers are used.

It is also used as a cosmetic raw material as an extract of Yukinoshita or Akamegashiwa. As used herein, Yukinoshita or Akamegashiwa is used for any of the naturally bred or cultivated Yukinoshita or Akagashiwiwa, such as Japan, Korea, China, Taiwan and other Asian countries, North America, South America, Oceania and Africa. Of these, those made in Japan and China are preferable because the use history of agricultural chemicals can be traced, the quality is stable, and the price is low.

The leaves or flowers of Yukinoshita or Akamegashiwa may be either fresh or dried.

It is preferable that the collected leaves or flowers of Yukinoshita or Akamegashiwa are washed with tap water.

The leaves or flowers of Yukinoshita or Akamegashiwa are crushed. For pulverization, free mill, super free mill, sample mill, goblin, super clean mill, micros, manufactured by Nara Machinery Co., Ltd. as a pulverizer, a small vacuum dryer manufactured by Toyo Riko as a vacuum dryer, manufactured by Matsui Co., Ltd. A small decompression heat transfer type dryer DPTH-40, clean dry VD-7, VD-20, etc. manufactured by AKM Kyushu Technos Co., Ltd. are used.

The eicosapentaenoic acid used here is preferably derived from fish and extracted from fish oil and purified, since it has few impurities. Eicosapentaenoic acid manufactured by Nippon Suisan is preferred because of its stable quality.

The transesterification lipase used here is, for example, a lipozyme or novozyme 435 manufactured by Novozyme, a lipase PL or lipase QLM manufactured by Meisho Sangyo, or a lipase AY “Amano” manufactured by Amano Enzyme. High quality products such as 30G, lipase G “Amano” 50, lipase F-AP15, and neurase F3G are used, and these are preferable because their safety has been confirmed.

To the clean stainless steel cylinder, the above-mentioned pulverized leaves of Yukinoshita or Akamegashiwa or flowers, eicosapentaenoic acid and lipase for transesterification are added and heated. Here, it is preferable to add tap water as a solvent from the viewpoint of smoothing the reaction.

The amount of eicosapentaenoic acid is preferably 0.01 to 0.6 weight, and the amount of transesterified lipase is preferably 0.0001 to 0.05 weight with respect to 1 weight of the pulverized product of leaves or flowers of Yukinoshita or Akamegashiwa.

The heating temperature is preferably 11 to 43 ° C, more preferably 12 to 38 ° C.

The heating time is preferably 1 to 48 hours, more preferably 2 to 36 hours.

The heating is preferably performed while stirring, and a rate of 10 to 150 times per minute is preferable.

It is cooled after being warmed. The cooling method is preferably natural cooling or water cooling.

The reactants are separated by vegetable oil. The reactant is soluble in vegetable oil because of its high oil solubility. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil Oils used in edible or cosmetic products such as wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil are used In addition, it is more preferable to use a vegetable oil containing a pine leaf extract, a kokushi extract, a green tea extract, a chrysanthemum extract or a bamboo leaf extract because the intended derivative is stably maintained.

In particular, the above-mentioned pine leaf extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding a vegetable oil to a pulverized product of pine leaves. Can be separated.

The pine leaves used for the pine leaf extract-containing vegetable oil may be any of Japanese, Chinese and Taiwanese.

Pine leaves cultivated without using pesticides are preferred because they can avoid the danger of pesticides.

The vegetable oil to be added is preferably 0.4 to 4 weights with respect to 1 weight of the pulverized product of the leaves or flowers of Yukinoshita or Akamegashiwa.

The separated bergenin derivative is absorbed into the body, and then the excess amount is decomposed by esterase and further metabolized in the liver. Therefore, safety is high and there are few side effects.

Separating and purifying the target bergenin derivative from the reaction product is preferable from the viewpoint that the intake can be reduced as a highly pure substance. As a purification method, it is preferable to use a purification operation such as an organic solvent for separation or a resin. As the organic solvent, ethanol, hexane, chloroform, benzene, ethyl acetate, ether and the like are used, and among these, ethanol for food processing or hydrous ethanol is more preferable because it is easy to handle.

As the separation resin, porous polysaccharides, silicon oxide compounds, polyacrylamide, polystyrene, polypropylene, styrene-vinylbenzene copolymers, etc. whose surfaces are coated are used. It is preferable that the target bergenin derivative is obtained by separation with an appropriate separation solvent, purification, and removal of the solvent.

The bergenin derivative thus obtained is obtained as a liquid or powder. The obtained bergenin derivative is used for pharmaceuticals, food preparations or cosmetics. As pharmaceuticals, they are used as anti-inflammatory agents, anti-obesity agents, lipolytic agents, wrinkle removing agents, fatty liver inhibitors, hyperlipidemia improving agents, anti-arteriosclerotic agents, anti-allergic agents and the like.

The food preparation is used for anti-inflammatory, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, improvement of metabolic syndrome, nutrition tonic, maintenance of liver function, etc. The

This cosmetic product exhibits anti-inflammatory effects by suppressing the production of inflammatory cytokines, and also exhibits vasodilatory effects on the skin and limba tube dilation, so it suppresses wrinkles and sagging caused by inflammation such as sunburn. Or it is effective for prevention of production. In particular, it exerts anti-inflammatory action against inflammation caused by sunburn, and removes the cause of wrinkles and sagging.

Furthermore, this cosmetic exhibits an excellent therapeutic or preventive action against atopic dermatitis in which inflammatory cytokines are produced in large quantities.

Next, among bergenin derivatives represented by the above formula (1) obtained by adding docosahexaenoic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating and extracting with vegetable oil, A bergenin derivative represented by the following formula (5) having an inhibitory action on inflammatory cytokine production, wherein Z is docosahexaenoic acid, will be described.

Here, the bergenin derivative is the bergenin derivative described above, and is a derivative in which carboxylic acid of docosahexaenoic acid is ester-bonded to bergenin. X is a methyl group, Y is hydrogen, and Z is docosahexaenoic acid.

The bergenin derivative suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8 and TNF alpha.

The bergenin derivative passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, moves into the nucleus, and acts on transcription factors such as NF-kappa B and NF-IL6. Suppresses the production of proinflammatory cytokines by suppressing the gene level expression of sex cytokines. Further, in the above-mentioned bergenin derivative, a saturated fatty acid residue of docosahexaenoic acid penetrates into the cell membrane, is easily absorbed into the cell, is easy to act on the target protein kinase C, and is preferably enhanced in anti-inflammatory action.

The bergenin derivative is obtained by adding docosahexaenoic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating, and extracting with vegetable oil.

The plant used is Yukinoshita or Akamegasiwa. Yukinoshita or Akamegashiwa are grown or grown in books, Asia, and around the world. Both have been used for folk medicine and medicinal dishes for a long time, have abundant dietary experience, and have been confirmed to be safe. The leaves or flowers of these plants are used.

It is also used as a cosmetic raw material as an extract of Yukinoshita or Akamegashiwa. As used herein, Yukinoshita or Akamegashiwa is used for any of the naturally bred or cultivated Yukinoshita or Akagashiwiwa, such as Japan, Korea, China, Taiwan and other Asian countries, North America, South America, Oceania and Africa. Of these, those made in Japan and China are preferable because the use history of agricultural chemicals can be traced, the quality is stable, and the price is low.

The leaves or flowers of Yukinoshita or Akamegashiwa may be either fresh or dried.

It is preferable that the collected leaves or flowers of Yukinoshita or Akamegashiwa are washed with tap water.

The leaves or flowers of Yukinoshita or Akamegashiwa are crushed. A pulverizer is used for pulverization, for example, a free mill, super free mill, sample mill, goblin, super clean mill, micros, manufactured by Nara Machinery Co., Ltd., a small vacuum dryer manufactured by Toyo Riko as a vacuum dryer, A compact decompression heat transfer dryer DPTH-40 manufactured by Matsui Co., Ltd., clean dry VD-7, VD-20 manufactured by AKM Kyushu Technos Co., Ltd., etc. are used.

The docosahexaenoic acid used here is preferably derived from fish and extracted from fish oil and purified, since it has few impurities. Docosahexaenoic acid manufactured by Nippon Suisan is preferred because of its stable quality.

The transesterification lipase used here is, for example, a lipozyme or novozyme 435 manufactured by Novozyme, a lipase PL or lipase QLM manufactured by Meisho Sangyo, or a lipase AY “Amano” manufactured by Amano Enzyme. High quality products such as 30G, lipase G “Amano” 50, lipase F-AP15, and neurase F3G are used, and these are preferable because their safety has been confirmed.

To the clean stainless steel cylinder and the like, the above-mentioned pulverized leaves of Yukinoshita or Akamegashiwa or flowers, docosahexaenoic acid and lipase for transesterification are added and heated. Here, it is preferable to add tap water as a solvent from the viewpoint of smoothing the reaction.

The amount of docosahexaenoic acid is preferably 0.02 to 0.5 weight and the amount of lipase for transesterification is preferably 0.0001 to 0.05 weight with respect to 1 weight of the pulverized product of leaves or flowers.

The heating temperature is preferably 11 to 48 ° C, more preferably 13 to 36 ° C.

The heating time is preferably 1 to 48 hours, more preferably 2 to 36 hours.

The heating is preferably performed while stirring, and a rate of 10 to 130 times per minute is preferable.

It is cooled after being warmed. The cooling method is preferably natural cooling or water cooling.

Since the reactant is highly oil-soluble, it dissolves in vegetable oil and is separated by vegetable oil using its properties. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil Oils used in edible or cosmetic products such as wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil are used In addition, it is more preferable to use a vegetable oil containing a pine leaf extract, a kokushi extract, a green tea extract, a chrysanthemum extract or a bamboo leaf extract because the intended derivative is stably maintained.

In particular, the above-mentioned pine leaf extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding a vegetable oil to a pulverized product of pine leaves. Can be separated.

The pine leaves used for the pine leaf extract-containing vegetable oil may be any of Japanese, Chinese and Taiwanese.

Pine leaves cultivated without using pesticides are preferred because they can avoid the danger of pesticides.

The vegetable oil to be added is preferably 0.4 to 4 weights with respect to 1 weight of the pulverized product of the leaves or flowers of Yukinoshita or Akamegashiwa.

The separated bergenin derivative is absorbed into the body, and then the excess amount is decomposed by esterase and further metabolized in the liver. Therefore, safety is high and there are few side effects.

Separating and purifying the target bergenin derivative from the reaction product is preferable from the viewpoint that the intake can be reduced as a highly pure substance. As a purification method, it is preferable to use a purification operation such as an organic solvent for separation or a resin. As the organic solvent, ethanol, hexane, chloroform, benzene, ethyl acetate, ether and the like are used, and among these, ethanol for food processing or hydrous ethanol is more preferable because it is easy to handle.

As the separation carrier or resin, porous polysaccharide, silicon oxide compound, polyacrylamide, polystyrene, polypropylene, styrene-vinylbenzene copolymer, etc., whose surface is coated, are used. It is preferable that the target bergenin derivative is obtained by separation with an appropriate separation solvent, purification, and removal of the solvent.

The bergenin derivative thus obtained is obtained as a liquid or powder. The obtained bergenin derivative is used for pharmaceuticals, food preparations or cosmetics. As pharmaceuticals, they are used as anti-inflammatory agents, anti-obesity agents, lipolytic agents, wrinkle removing agents, fatty liver inhibitors, hyperlipidemia improving agents, anti-arteriosclerotic agents, anti-allergic agents and the like.

The food preparation is used for anti-inflammatory, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, improvement of metabolic syndrome, nutrition tonic, maintenance of liver function, etc. The

This cosmetic product exhibits anti-inflammatory effects by suppressing the production of inflammatory cytokines, and also exhibits vasodilatory effects on the skin and limba tube dilation, so it suppresses wrinkles and sagging caused by inflammation such as sunburn. Or it is effective for prevention of production. In particular, it exerts anti-inflammatory action against inflammation caused by sunburn, and removes the cause of wrinkles and sagging.

Furthermore, this cosmetic exhibits an excellent therapeutic or preventive action against atopic dermatitis in which inflammatory cytokines are produced in large quantities.

Next, a bergenin derivative having an inflammatory cytokine production inhibitory action obtained by extracting a fermented product obtained by adding fermented natto to fermented fish, saxifrage or red wrinkle leaves or flowers and soybeans with a vegetable oil will be described.

The bergenin derivative having an inhibitory action on inflammatory cytokine production here is the bergenin derivative described above.

That is, it is a derivative in which any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid is bonded to bergenin.

In this bergenin derivative, a carboxylic acid of any one of palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid is ester-bonded.

In this case, the structure of bergenin is stabilized by binding of palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid. Has features.

The bergenin derivative suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8 and TNF alpha.

The above-mentioned bergenin derivative passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, and suppresses the expression of protein kinase C, which plays a central role in inflammation signals, thereby inhibiting the production of inflammatory cytokines. Suppress.

The aforementioned bergenin derivative is bonded with any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid, which have high fat-soluble characteristics. Therefore, it is easy to be familiar with the cell membranes of the small intestine and skin, and is easily absorbed.

When the bergenin derivative is ingested and absorbed excessively, the excess amount is degraded by esterase in the blood and bergenin and its respective palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha -Since it is decomposed into any of lipoic acid, gamma-linolenic acid and stearic acid, each of which has been confirmed to be safe, the above-mentioned bergenin derivative is also highly safe. At this time, X and Y may be either hydrogen or a methyl group.

Among the above-mentioned bergenin derivatives, when Z is palmitic acid, saturated fatty acid residues of palmitic acid penetrate into the cell membrane, are easily absorbed into cells, work easily on the target protein kinase C, and have an enhanced anti-inflammatory effect. Is preferable.

Among the above-mentioned bergenin derivatives, when Z is gallic acid, the hydroxy residue of gallic acid penetrates into the cell membrane, exhibits an antioxidant action, stably maintains the cell membrane, and easily acts on the target protein kinase C. The anti-inflammatory action is preferably enhanced.

Among the above-mentioned bergenin derivatives, when Z is eicosapentaenoic acid, the unsaturated fatty acid residue of eicosapentaenoic acid exhibits inflammatory prostaglandin production inhibitory action, so the amount of inflammatory prostaglandin produced from arachidonic acid is reduced. This is preferable because the anti-inflammatory effect is enhanced.

Among the above bergenin derivatives, when Z is docosahexaenoic acid, unsaturated fatty acid residues of docosahexaenoic acid exhibit platelet aggregation inhibition and arterial dilation effects, thereby improving blood flow and enhancing anti-inflammatory effects. To preferred.

Among the above-mentioned bergenin derivatives, when Z is docosapentaenoic acid, the unsaturated fatty acid residue of docosapentaenoic acid exhibits a capillary dilation effect, thereby improving blood flow in the inflammatory region and excretion of inflammatory substances. Is preferred because the anti-inflammatory action is enhanced.

Among the bergenin derivatives, when Z is gamma-linolenic acid, an unsaturated fatty acid residue of gamma-linolenic acid is preferable because it suppresses the reaction of inflammatory prostaglandins and increases the anti-inflammatory action.

Among the above-mentioned bergenin derivatives, when Z is alpha-lipoic acid, the SH group of alpha-lipoic acid exhibits an anti-oxidant action, which prevents tissue damage against oxidative stress and enhances the anti-inflammatory action. preferable.

Among the bergenin derivatives, when Z is stearic acid, the saturated fatty acid residue of stearic acid penetrates into the cell membrane and is easily absorbed into the cell, easily acting on the target protein kinase C, and the anti-inflammatory effect is enhanced. Is preferable.

The bergenin derivative is obtained by extracting a fermented product obtained by adding fermented natto bacteria to edible fish, saxifrage or red wrinkle leaves or flowers and soybeans with vegetable oil. As used herein, edible fish refers to fish used for food, and among them, eels have abundant food experience.

The head and internal organs of eel have dietary experience and contain fatty acids such as palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, etc. preferable.

In the fishery, eel heads and internal organs are discarded in the processing process, which is preferable because waste can be used effectively.

Of these, eels grown and grown on the shores of Lake Hamana are preferred.

Moreover, it is preferable to dismantle after slaughtering at a dismantling site, cut the head and internal organs, and collect.

It is preferable to cut the collected eel head and internal organs with a knife and pulverize them with DM-6 manufactured by Nakayama Institute of Technology.

The plant used is Yukinoshita or Akamegasiwa. The leaves or flowers of Yukinoshita or Akamegasiwa grown in Japan, Asia, or other countries are used.

Among these, the leaves or flowers of Yukinoshita or Akamegashiwa contain a large amount of the target bergenin and are preferable because they are extracted, and are discarded as natural waste, reducing waste and preventing environmental pollution. It is preferable because it is possible.

It is preferable that the leaves or flowers of Yukinoshita or Akamegasiwa are pulverized by a pulverizer such as DM-6 manufactured by Nakayama Institute of Technology.

Soybean here can be used from any origin, such as from Japan, China, the United States, or Russia, and is preferably pulverized by a pulverizer such as DM-6 manufactured by Nakayama Technical Research Laboratory.

The natto bacteria here are a kind of Bacillus subtilis used for the processing of natto and food. Natto bacteria manufactured by Natto Motopo are preferred because they are suitable for fermentation.

The amount of each of the above-mentioned fermentations is preferably 0.02 to 0.4 weight for the leaves or flowers of Yukinoshita or Akamegashiwa, 1 to 4 weights for soybean, and 0.1 to 4 weights for soybean, 0.001 to 0.04 weight is preferred.

The fermentation is carried out in a clean culture tank, and it is preferable to mix the materials with tap water.

Moreover, this fermentation is heated at 31-50 degreeC, and fermentation is performed for 22-73 hours. After fermentation, in order to carry out the extraction efficiently, it is diluted with tap water.

Since the said fermented material has the property to melt | dissolve in vegetable oil from oil solubility being high, it isolate | separates with vegetable oil. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil Oils used in edible or cosmetic products such as wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil are used In addition, it is more preferable to use a vegetable oil containing a pine leaf extract, a kokushi extract, a green tea extract, a chrysanthemum extract or a bamboo leaf extract because the intended derivative is stably maintained.

In particular, the above-mentioned pine leaf extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding a vegetable oil to a pulverized product of pine leaves. Can be separated.

The pine leaves used for the pine leaf extract-containing vegetable oil may be any of Japanese, Chinese and Taiwanese.

Pine leaves cultivated without using pesticides are preferred because they can avoid the danger of pesticides.

The addition amount of vegetable oil is 0.01-3 weight with respect to 1 weight of said fermented material. In this case, extraction by stirring is preferable, the stirring temperature is preferably 11 to 49 ° C., and the stirring time is preferably 30 minutes to 5 hours.

After the stirring, it is preferable to collect the pine leaf extract-containing vegetable oil separated in the upper layer and remove the water. In order to remove moisture, a dryer such as TGD-250LF2 manufactured by Toyo Giken is used.

The separated bergenin derivative is absorbed into the body, and then the excess amount is decomposed by digestive enzymes such as esterase and further metabolized in the liver. Therefore, safety is high and there are few side effects.

Separating and purifying the target bergenin derivative from the reaction product is preferable from the viewpoint that the intake can be reduced as a highly pure substance. As a purification method, it is preferable to use a purification operation such as an organic solvent for separation or a resin. As the organic solvent, ethanol, hexane, chloroform, benzene, ethyl acetate, ether and the like are used, and among these, ethanol for food processing or hydrous ethanol is more preferable because it is easy to handle.

As the separation carrier or resin, porous polysaccharide, silicon oxide compound, polyacrylamide, polystyrene, polypropylene, styrene-vinylbenzene copolymer, etc., whose surface is coated, are used. It is preferable that the target bergenin derivative is obtained by separation with an appropriate separation solvent, purification, and removal of the solvent.

The bergenin derivative thus obtained is obtained as a liquid or powder. The obtained bergenin derivative is used for pharmaceuticals, food preparations or cosmetics. As pharmaceuticals, they are used as anti-inflammatory agents, anti-obesity agents, lipolytic agents, wrinkle removing agents, fatty liver inhibitors, hyperlipidemia improving agents, anti-arteriosclerotic agents, anti-allergic agents and the like.

The food preparation is used for anti-inflammatory, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, improvement of metabolic syndrome, nutrition tonic, maintenance of liver function, etc. The

This cosmetic product exhibits anti-inflammatory effects by suppressing the production of inflammatory cytokines, and also exhibits vasodilatory effects on the skin and limba tube dilation, so it suppresses wrinkles and sagging caused by inflammation such as sunburn. Or it is effective for prevention of production. In particular, it exerts anti-inflammatory action against inflammation caused by sunburn, and removes the cause of wrinkles and sagging.

Furthermore, this cosmetic exhibits an excellent therapeutic or preventive action against atopic dermatitis in which inflammatory cytokines are produced in large quantities.

Next, 0.01 to 0.5 weight of chrysanthemum flower extract-containing vegetable oil and 0.01 to 0.5 weight of vegetable oil containing pine leaf extract are contained in 1 weight of the bergenin derivative having an inhibitory action on inflammatory cytokine production. A food preparation comprising the composition will be described.

The bergenin derivative having an inhibitory action on the production of inflammatory cytokines herein may be any of a crude product, a mixture, a synthesized product, and a highly purified substance extracted and purified. Z is a derivative in which any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid is ester-linked. At the same time, X or Y may be either hydrogen or a methyl group.

Further, the bergenin derivative here is a derivative that suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8, and TNF alpha.

Furthermore, the bergenin derivative here passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, moves into the nucleus and acts on transcription factors such as NF-kappa B and NF-IL6, and transcription. A factor is a derivative that suppresses gene-level expression of inflammatory cytokines and suppresses the production of inflammatory cytokines.

Here, the chrysanthemum flower extract-containing vegetable oil is a vegetable oil comprising a chrysanthemum flower extract containing polyphenols, and is obtained by extracting a chrysanthemum flower or a fermented chrysanthemum flower with a vegetable oil.

The vegetable oils used in the chrysanthemum flower extract-containing vegetable oil include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, Edible oil such as canola oil, grape seed oil, sesame oil, wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil Or the oil used for cosmetics is used.

Chrysanthemum flower extract-containing vegetable oil manufactured by Toyo Fermentation Co., Ltd. is preferable because of its high quality and low impurities.

The pine leaf extract-containing vegetable oil is obtained by pulverizing Japanese, Chinese and Asian pine, red pine, black pine and other French pine pine leaves with a pulverizer and extracting them with vegetable oil.

Processed raw material of pine leaves with cellulase such as Onozuka R-10, Y-NC manufactured by Yakult Pharmaceutical Co., Ltd., Cellulase A “Amano” 3 and Cellulase T “Amano” 4 manufactured by Amano Enzyme Co., Ltd. This is preferable because the extraction efficiency is improved. A pine leaf extract-containing vegetable oil manufactured by Toyo Fermentation Co., Ltd. is preferable because of its high quality and low impurities.

The added chrysanthemum flower extract-containing vegetable oil is 0.01-0.5 wt. And the pine leaf extract-containing vegetable oil is 0.01-0. .5 weight, which gives a composition.

If the weight of the chrysanthemum flower extract-containing vegetable oil is less than 0.01 wt. Per 1 wt. Of the bergenin derivative, the intended composition may not be sufficiently obtained.

When the weight of the chrysanthemum flower extract-containing vegetable oil is more than 0.5 weight with respect to 1 weight of the bergenin derivative, the solubility of the bergenin derivative is lowered and may be precipitated.

If the weight of the pine leaf extract-containing vegetable oil is less than 0.01 wt. Per 1 wt. Of the bergenin derivative, the intended composition may not be sufficiently obtained.

When the weight of the pine leaf extract-containing vegetable oil is more than 0.5 weight relative to 1 weight of the bergenin derivative, the solubility of the bergenin derivative is lowered and may be precipitated.

In order to obtain the said composition, it is preferable to heat after mixing. As heating conditions, the temperature is 29 to 46 ° C., and the heating time is 5 to 41 hours.

When the heating temperature is below 29 ° C, there is a possibility that sufficient reaction may not occur. When the heating temperature is higher than 46 ° C., the reaction product generated by oxidation may turn brown. When the heating time is less than 5 hours, there is a possibility that a sufficient product cannot be obtained. If the warming time exceeds 41 hours, the product produced by oxidation may turn brown.

This composition is preferable because the above-mentioned bergenin derivative is continuously released little by little and becomes a continuous composition.

Moreover, by comprising in this way, a bergenin derivative is stably maintained by the antioxidant power of a chrysanthemum flower extract containing vegetable oil, and the decomposition | disassembly by oxidation is suppressed. In particular, double bonds of unsaturated fatty acids are protected from oxidation and maintain the structure.

Further, the composition is processed together with other raw materials to form a food preparation. In this case, by adding to various food materials or beverage materials, for example, it can be made into a food preparation in the form of powder, tablet, liquid (drink, etc.), capsule or 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 0.2 to 10 g, more preferably 0.3 to 6 g, and even more preferably 0.5 to 4 g. If the daily intake is less than 0.2 g, sufficient anti-inflammatory action 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 and the like.

The food preparation referred to here is a health functional food, health supplement food, general food, hospital food used in a hospital, animal feed, pet supplement, or pet food.

This food preparation is used for anti-inflammatory, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, improvement of metabolic syndrome, nourishing tonic, maintenance of liver function, etc. .

Next, 1 weight of the bergenin derivative having an inhibitory action on inflammatory cytokine production contains 0.05 to 0.8 weight of chrysanthemum flower extract-containing vegetable oil and 0.05 to 0.8 weight of pine leaf extract-containing vegetable oil. A cosmetic product comprising the composition will be described.

The bergenin derivative having an inhibitory action on the production of inflammatory cytokines herein may be any of a crude product, a mixture, a synthesized product, and a highly purified substance extracted and purified. In addition, any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid and stearic acid is an ester-linked derivative.

Further, the bergenin derivative here is a derivative that suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8, and TNF alpha.

Furthermore, the bergenin derivative here passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, moves into the nucleus and acts on transcription factors such as NF-kappa B and NF-IL6, and transcription. A factor is a derivative that suppresses gene-level expression of inflammatory cytokines and suppresses the production of inflammatory cytokines.

Here, the chrysanthemum flower extract-containing vegetable oil is a vegetable oil comprising a chrysanthemum flower extract containing polyphenols, and is obtained by extracting a chrysanthemum flower or a fermented chrysanthemum flower with a vegetable oil.

The vegetable oils used in the chrysanthemum flower extract-containing vegetable oil include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, Edible oil such as canola oil, grape seed oil, sesame oil, wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil Or the oil used for cosmetics is used.

Chrysanthemum flower extract-containing vegetable oil manufactured by Toyo Fermentation Co., Ltd. is preferable because of its high quality and low impurities.

The pine leaf extract-containing vegetable oil is obtained by pulverizing Japanese, Chinese and Asian pine, red pine, black pine and other French pine pine leaves with a pulverizer and extracting them with vegetable oil.

Processed raw material of pine leaves with cellulase such as Onozuka R-10, Y-NC manufactured by Yakult Pharmaceutical Co., Ltd., Cellulase A “Amano” 3 and Cellulase T “Amano” 4 manufactured by Amano Enzyme Co., Ltd. This is preferable because the extraction efficiency is improved. A pine leaf extract-containing vegetable oil manufactured by Toyo Fermentation Co., Ltd. is preferable because of its high quality and low impurities.

Chrysanthemum flower extract-containing vegetable oil is added in an amount of 0.05 to 0.8 wt., And pine needle extract-containing vegetable oil is added in an amount of 0.05 to 0 with respect to 1 wt. Of the bergenin derivative having an inhibitory action on inflammatory cytokine production. 0.8 weight, which gives a composition.

When the weight of the chrysanthemum flower extract-containing vegetable oil is less than 0.05 weight with respect to 1 weight of the bergenin derivative, the target composition may not be sufficiently obtained.

When the weight of the vegetable oil containing chrysanthemum flower extract exceeds 0.8 weight with respect to 1 weight of the bergenin derivative, the solubility of the bergenin derivative is lowered and may be precipitated.

When the weight of the pine leaf extract-containing vegetable oil is less than 0.05 weight per 1 weight of the bergenin derivative, the target composition may not be sufficiently obtained.

When the weight of the pine leaf extract-containing vegetable oil is more than 0.8 weight with respect to 1 weight of the bergenin derivative, the solubility of the bergenin derivative is lowered and may be precipitated.

In order to obtain the said composition, it is preferable to heat after mixing. As heating conditions, the temperature is 29 to 46 ° C., and the heating time is 5 to 41 hours.

When the heating temperature is below 29 ° C, there is a possibility that sufficient reaction may not occur. When the heating temperature is higher than 46 ° C., the reaction product generated by oxidation may turn brown. When the heating time is less than 5 hours, there is a possibility that a sufficient product cannot be obtained.

If the warming time exceeds 41 hours, the product produced by oxidation may turn brown.

This composition is preferable because the above-mentioned bergenin derivative is continuously released little by little and becomes a continuous composition.

Moreover, by comprising in this way, a bergenin derivative is stably maintained by the antioxidant power of a chrysanthemum flower extract containing vegetable oil, and the decomposition | disassembly by oxidation is suppressed. In particular, double bonds of unsaturated fatty acids are protected from oxidation and maintain the structure.

Furthermore, the composition is processed together with other raw materials as a cosmetic. Thereafter, it can be used together with oils, surfactants, vitamins, ultraviolet absorbers, thickeners, moisturizers, auxiliary materials and the like in accordance with conventional methods.

It can be in the form of lotion, cream, ointment, lotion, milky lotion, pack, oil, soap, face wash, fragrance, audi cologne, bath preparation, shampoo, rinse and the like. The form of the cosmetic preparation is arbitrary, and can be used as a solution, cream, paste, gel, gel, solid, or powder.

As a cosmetic, it is applied to the skin several times a day. The daily coating amount is preferably 0.01 to 10 g, more preferably 0.05 to 3 g, and further preferably 0.1 to 2 g. When the daily application amount is less than 0.01 g, the treatment or prevention effect of wrinkles and sagging may not be exhibited. When the application amount per day exceeds 10 g, the cost may increase.

The cosmetics referred to here are basic cosmetics, whitening cosmetics, hair cleansing agents, treatment agents, dyeing agents, hair restorers, hair nourishing agents, body wash, quasi-drugs, which are cosmetics used for humans. In addition, it is a skin improvement agent used for animals, a shampoo for pets, and a body wash.

This cosmetic product exhibits anti-inflammatory effects by suppressing the production of inflammatory cytokines, and also exhibits vasodilatory effects on the skin and limba tube dilation, so it suppresses wrinkles and sagging caused by inflammation such as sunburn. Or it is effective for prevention of production.

In particular, it exerts anti-inflammatory action against inflammation caused by sunburn, and removes the cause of wrinkles and sagging.

Furthermore, this cosmetic exhibits an excellent therapeutic or preventive action against atopic dermatitis in which inflammatory cytokines are produced in large quantities.

Next, the anti-inflammatory agent comprising a bergenin derivative having an inhibitory action on inflammatory cytokine production will be described.

The bergenin derivative having an inhibitory action on the production of inflammatory cytokines herein may be any of a crude product, a mixture, a synthesized product, and a highly purified substance extracted and purified. In addition, any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid and stearic acid is an ester-linked derivative.

Further, the bergenin derivative here is a derivative that suppresses the production of inflammatory cytokines such as interleukin-1 alpha, interleukin-8, and TNF alpha.

Furthermore, the bergenin derivative here passes through the cell membrane of inflammatory cells such as monocytes, macrophages, and neutrophils, moves into the nucleus and acts on transcription factors such as NF-kappa B and NF-IL6, and transcription. A factor is a derivative that suppresses gene-level expression of inflammatory cytokines and suppresses the production of inflammatory cytokines.

When used as a pharmaceutical, it is necessary to remove the influence of impurities, and therefore it is preferable to use a bergenin derivative having the structure described above, which is synthesized by an enzymatic reaction and has little solvent residue.

It is used as a pharmaceutical orally or parenterally, and as a quasi-drug, it is used by blending with 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 above syrup and drink, sweeteners, preservatives, pigment 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. As the base material of the external preparation used here, petrolatum, paraffin, fats and oils, lanolin, macro gold and the like are used, and an ointment, a cream and the like can be obtained by a usual method.

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.

The anti-inflammatory agent here is a pharmaceutical product or quasi-drug preparation for the purpose of treating or preventing skin, systemic or local inflammation.

Systemic inflammation includes fever, redness, and edema. Pneumonia, encephalitis, pharyngitis, bronchitis, keratitis, enteritis, gastritis, duodenal inflammation, colitis, hepatitis, nephritis, cystitis , Pancreatitis, neuritis, myositis, arteritis, dermatitis, atopic dermatitis, dermatitis due to sunburn, etc. Especially, it is used as an external preparation for dermatitis due to sunburn.

The effect is exerted by an action mechanism that suppresses the production of inflammatory cytokines against inflammation of these whole body and local organs.

In addition, it can be used as a veterinary medicine for the treatment of inflammation and dermatitis in livestock and pets.

Hereinafter, the embodiment will be specifically described with reference to examples and test examples. In addition, the following description is an example and can be implemented changing a form.

First, the bergenin derivative obtained by fermentation will be described.

70 eels (scientific name: Angulara japonica) grown and grown on the shores of Lake Hamana were used as raw materials. The grown eels were slaughtered at a demolition site and then disassembled, and the head and internal organs were cut and collected. The body part was edible and the head and internal organs were collected.

The collected head and internal organs of 1.2 kg were cut with a knife and pulverized with DM-6 manufactured by Nakayama Institute of Technology.

This was placed in a clean culture tank and 3.1 L of tap water was added. After washing 1.5 kg of Yukinoshita leaves collected in Shizuoka Prefecture cultivated without chemicals with tap water, they were dried with a dryer (GZQ3 type, manufactured by Nishimura Kikai Co., Ltd.) and cut with scissors. The product was pulverized with DM-6. 150 g of this pulverized product was added to the above cylinder. To this, Chinese soybean was washed with water, heated to 37 ° C. for 34 minutes, and further 1.4 kg of soybean ground material was added.

To this, 14 g of natto bacteria manufactured by Natto Motopo was added. Fermentation was continued for 45 hours at 36 ° C. with stirring.

3.4 L of tap water was added to the tank after the fermentation. This was made into a fermented product.

0.8 kg of Ajinomoto soybean oil was added to the fermented product, and the mixture was stirred for 1 hour and mixed.

This was allowed to stand, and the oil-soluble portion separated by soybean oil separated into the upper layer was collected as a liquid. In order to remove water, it was subjected to TGD-250LF2 manufactured by Toyo Giken, and the target bergenin derivative was obtained as an oily substance. This was used as the sample of Example 1.

The preparation of a bergenin derivative covalently bound to palmitic acid is described below.

1 kg of leaves from Shizuoka grown in pesticide-free was purchased, washed thoroughly with tap water, and dried with a dryer.

1 kg of this Yukinoshita leaf was subjected to a pulverizer (manufactured by Sanriki Seisakusho Co., Ltd., Sanroku universal pulverizer) and pulverized to obtain a green tea pulverized product.

1 kg of ground pulverized leaves of Yukinoshita or Akamegashiwa was put into a clean cylinder and 10 L of tap water was added. To this, 260 g of palmitic acid purchased from Ryoshoku was added and stirred.

To this was added 10 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 30 ° C. and stirred at a rate of 80 times / minute for 14 hours to obtain a heated solution.

After cooling the cylinder containing the warming solution with tap water, 1.0 kg of Ajinomoto soybean oil was added, and the oil portion was collected.

This oil part was dried with a vacuum dryer (manufactured by AKM Kyushu Technos, Clean Dry) to obtain a bergenin derivative bound with palmitic acid as an oily liquid. This was also used as the sample of Example 2.

The preparation of a bergenin derivative to which gallic acid is bound is described below.

3 kg of leaves from Shizuoka grown in pesticide-free were collected, washed thoroughly with tap water, and dried with a dryer (GZQ3 type, manufactured by Nishimura Kikai). This was used as the raw leaves of Yukinoshita.

3 kg of this Yukinoshita leaf was subjected to a pulverizer (manufactured by Sanriki Seisakusho Co., Ltd., a three-purpose universal pulverizer) and pulverized to obtain a pulverized product of Yukinoshita leaf.

1.1 kg of pulverized leaves of Yukinoshita were put into a clean cylinder and 10 L of tap water was added. To this, 210 g of gallic acid purchased from Ryoshoku was added and stirred.

To this was added 18 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 30 ° C. and stirred at a rate of 68 times / min for 15 hours to obtain a heated solution.

After cooling the cylinder containing the warming liquid with tap water, 1 kg of RIKEN vitamin palm oil was added, and the oil portion was collected.

This was dried with a vacuum dryer (manufactured by AKM Kyushu Technos, Clean Dry) to obtain a bergenin derivative to which gallic acid was bound as an oily liquid. This was also used as the sample of Example 3.

Hereinafter, preparation of a bergenin derivative to which eicosapentaenoic acid is bound will be described.

3 kg of Chinese red mulberry leaves grown without pesticides were collected, washed thoroughly with tap water, and dried with a dryer. This was used as the raw material of Akagasiwa. 2.3 kg of the leaves of the red mulberry were subjected to a pulverizer (manufactured by Sanriki Seisakusho Co., Ltd., a three-purpose universal pulverizer) and pulverized to obtain a pulverized product of red mulberry leaves.

1.4 kg of tap water was added to 1.4 kg of pulverized crushed leaves of Akegamega wrinkles in a clean cylinder. To this, 340 g of Eicosapentaenoic acid manufactured by Nippon Suisan was added and stirred.

To this was added 14 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 27 ° C. and stirred at a rate of 66 times / min for 14 hours to obtain a heated solution.

After cooling the cylinder containing the warming liquid with tap water, 1 kg of RIKEN vitamin palm oil was added, and the oil portion was collected.

This was dried by a vacuum drier (manufactured by AKM Kyushu Technos, Clean Dry) to obtain a bergenin derivative bound with eicosapentaenoic acid as an oily liquid. This was also used as the sample of Example 4.

Hereinafter, the preparation of a bergenin derivative to which docosahexaenoic acid is bound will be described.

3 kg of Japanese cypress leaves cultivated without pesticides were collected, thoroughly washed with tap water, and dried with a dryer (GZQ3 type, manufactured by Nishimura Kikai). This was used as the raw leaves of Yukinoshita.

2.6 kg of this Yukinoshita leaf was subjected to a pulverizer (Sanki Seisakusho universal pulverizer) and pulverized to obtain a pulverized product of Yukinoshita leaf.

1.2 kg of ground water was added to a clean cylinder and 12 L of tap water was added. To this, 360 g of docosahexaenoic acid manufactured by Nissui Pharmaceutical was added and stirred.

To this was added 12 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 26 ° C. and stirred at a rate of 70 times / min for 14 hours to obtain a heated solution.

After cooling the cylinder containing the warming liquid with tap water, 1 kg of pine leaf extract-containing coconut oil manufactured by Toyo Fermentation Co., Ltd. was added, and the oil portion was collected.

This was dried by a vacuum dryer (manufactured by AKM Kyushu Technos, Clean Dry) to obtain a bergenin derivative bound with docosahexaenoic acid as an oily liquid. This was also used as the sample of Example 5.

Hereinafter, a purified product of the bergenin derivative will be described.

18 g of the bergenin derivative obtained in Example 4 was suspended in 500 mL of ethanol and applied to a column packed with 750 g of Diaion made by Mitsubishi Chemical. This was washed with 900 mL of 10% ethanol-containing water. Further, after washing with 900 mL of 30% ethanol-containing water, elution was performed with 900 mL of 75% ethanol-containing water, and a fraction of 90% ethanol-containing water was collected.

This was subjected to a vacuum dryer to distill off ethanol and water, and then 5 g of an oily purified product of bergenin derivative was obtained by a freeze dryer manufactured by Nippon FD. This was used as the sample of Example 6.

Below, the identification test of a bergenin derivative is demonstrated.
(Test Example 1)
Each of the bergenin derivatives obtained in Example 1, Example 2, Example 3, Example 4, Example 5, Example 6 and Example 6 obtained as described above was dissolved in purified ethanol, and a high-speed mass spectrometer was provided. Analysis was performed by liquid chromatography (HPLC, Shimadzu Corporation).

Furthermore, it analyzed with the nuclear magnetic resonance apparatus (NMR, the Bruker make, AC-250).

As a result, from the sample of Example 1, bergenin in which palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid was bound to bergenin as a bergenin derivative. Derivatives have been identified.

Further, from the sample of Example 2, a bergenin derivative in which palmitic acid was bound to bergenin was identified. The carboxylic acid of palmitic acid had an ester bond.

Further, from the sample of Example 3, a bergenin derivative in which gallic acid was bonded to bergenin was identified. The carboxylic acid of gallic acid was ester-bonded.

Further, from the specimens of Example 4 and Example 6, a bergenin derivative in which eicosapentaenoic acid was bound to bergenin was identified. The carboxylic acid of eicosapentaenoic acid was ester-bonded.

Further, from the sample of Example 5, a bergenin derivative in which docosahexaenoic acid was bound to bergenin was identified. The carboxylic acid of docosahexaenoic acid was ester-bonded.

Below, the suppression test of inflammatory cytokine production of a bergenin derivative is demonstrated.
(Test Example 2)
In the test, heparinized blood was collected from 8 men aged 22 to 79 years old and 8 women aged 28 to 71 infected with skim pollinosis, and monocytes were cultured by MEM (Nissui Pharmaceutical). .

1000 monocytes were seeded in a culture dish having a diameter of 35 mm and cultured at 37 ° C. for 24 hours under 5% carbon dioxide gas.

To this, 10 ng of cedar pollen (manufactured by Funamishi) and the specimens obtained in Examples 1 to 6 were dissolved in dimethyl sulfoxide, and 1 ng of each was added, followed by 48 hours after the addition.

The culture supernatant was collected, and the amounts of interleukin-1 alpha, interleukin-6 and TNF alpha as inflammatory cytokines were quantified by an absorbance method using an ELISA kit (manufactured by Amgen).

As a solvent control, dimethyl sulfoxide was used instead of the specimen.

In addition, clobetasol propionate, which is a steroid agent, was used as a positive control.

As a result, in the case of the amount of interleukin-1 alpha, when the amount of the solvent control is 100%, it is 54% in Example 1, 52% in Example 2, and 52 in Example 3 depending on the amount of 1 ng of each specimen. %, 48% in Example 4, 32% in Example 5, and 22% in Example 6. In addition, clobetasol propionate was 59%.

Therefore, it was concluded that all of the samples of Examples 1 to 6 suppressed the production of interleukin-1 alpha with respect to cedar pollen.

In the case of the amount of interleukin-6, when the amount of the solvent control is 100%, the added amount of 1 ng of each sample is 71% in Example 1, 70% in Example 2, 73% in Example 3, It was 67% in Example 4, 61% in Example 5, and 59% in Example 6. In addition, clobetasol propionate was 74%.

Therefore, it was concluded that all of the samples of Examples 1 to 6 suppressed the production of interleukin-6 against cedar pollen.

Further, in the case of the amount of TNF alpha, when the amount of the solvent control is 100%, the added amount of 1 ng of each sample is 59% in Example 1, 62% in Example 2, 51% in Example 3, and Example It was 45% in Example 4, 50% in Example 5, and 31% in Example 6. In addition, clobetasol propionate was 77%.

Therefore, it was concluded that all of the samples of Examples 1 to 6 suppressed the production of TNF alpha against cedar pollen.

As a result, the samples of Examples 1 to 6 were considered to suppress the production of inflammatory cytokines to the same extent or more than clobetasol propionate.

Below, manufacture of the foodstuff formulation containing a bergenin derivative is described.

100 g of the bergenin derivative obtained in Example 1 was placed in a food processing mixer (Tsukasa, Pow mixer, single type), and 40 g of chrysanthemum flower extract-containing vegetable oil manufactured by Toyo Fermentation Co., Ltd. was added. To this, 39 g of pine leaf extract-containing soybean oil manufactured by Toyo Fermentation Co., Ltd. was added, and this was heated at 38 ° C. for 25 hours with stirring and cooled to obtain about 166 g of a composition.

To 130 g of this composition, 330 g of edible cellulose, 1.2 g of ascorbic acid and 10 g of edible fragrance were added to a food processing mixer (Tsukasa, Pow mixer, W type) and mixed. This was pulverized by a conventional method, dried, and then filled into porcine-derived gelatin hard capsules as 250 mg per capsule to obtain a food preparation. This was used as the sample of Example 7.

Hereinafter, test examples using the specimen of Example 7 will be described.
(Test Example 3)

Eleven men presenting scabs and honeyworms due to house dust mites aged 23 to 76 years old, 10 capsules of the food preparation obtained in Example 7 once a day, that is, 2.5 g per day, every day for 28 days Feeded. The reactivity of house dust mites was observed before feeding and on the 28th day of feeding. Furthermore, blood was collected before feeding and on the 28th day of feeding, and the IgE amount was measured by an immunoantibody method.

As a result, after feeding, the number of mite and honey caterpillars caused by house dust mites was 32% on average compared to before feeding, and a clear decrease in reactivity was observed. Moreover, the blood IgE amount was 44% on average compared to before feeding, and a decrease in the IgE amount was observed. In addition, no abnormalities were observed in physical condition or health after eating.

Below, manufacture of the cosmetics containing a bergenin derivative is described.

105 g of the bergenin derivative obtained in Example 2 was placed in a cosmetic processing mixer (Pole Container Mixer, manufactured by Kotobuki Kogyo Co., Ltd.) and 52 g of chrysanthemum flower extract-containing vegetable oil manufactured by Toyo Fermentation Co., Ltd. was added. To this was added 51 g of pine leaf extract-containing soybean oil manufactured by Toyo Fermentation Co., Ltd., and this was heated at 37 ° C. for 34 hours with stirring to obtain about 187 g of a composition.

This composition was put into the mixer, and beeswax (manufactured by API) 100 g, petrolatum 300 g and squalane (manufactured by Nippon Suisan) 1 g were added and mixed to obtain a cream as a cosmetic preparation. This was used as the sample of Example 8. At the same time, a base-only cream excluding the bergenin derivative obtained in Example 2 was prepared.

The test example of the sample of Example 2 is described below.
(Test Example 4)
Using the cream obtained in Example 8, a wrinkle improvement test for ultraviolet rays was conducted on 14 women aged 25 to 68 years. That is, 14 cases were divided into 2 groups, and 1 g per day of the cream containing the bergenin derivative of Example 8 was applied to the face portion for 14 days. At the same time, a group using a cream containing only the base material was set.

The woman was exposed to ultraviolet rays for 1 hour every day with an ultraviolet irradiation device for sunburn (Neotan 888, manufactured by Emrock). Before use and after 14 days of use, skin skin temperature and skin area per unit area using skin elasticity, skin surface horny layer moisture measuring device (IBBS, SKICON 200) using keratin moisture, elasticity meter (Cutometer) The wrinkle length was measured.

Furthermore, sweat and sebum were collected, and the amount of TNF alpha, which is an inflammatory cytokine, was measured by an immunoenzymatic method (manufactured by Amgen).

As a result, in the usage example of the cream containing the bergenin derivative as compared with the cream using only the base material, a skin temperature decrease of 0.35 ° C. was recognized as an average value. Moreover, the skin surface angle layer water content increased to 169% in the use example of the cream containing the bergenin derivative as compared with the cream use of the base material alone. Further, the elasticity of the elasticity meter was increased to 189% in the usage example of the cream containing the bergenin derivative as compared to the cream using the base material alone.

The length of the wrinkle was 47% in the use example of the cream containing the bergenin derivative as compared with the use of the cream containing only the base material, and a decrease in wrinkle was clearly observed.

In addition, the amount of TNF alpha in sweat and sebum was reduced to an average of 56% in the use case of the cream containing the bergenin derivative compared to the use of the base material cream alone.

Furthermore, the cream containing the bergenin derivative showed no side effects and good usability.

Therefore, the cream of Example 8 was confirmed to have the effect of suppressing cytokine production due to ultraviolet rays and improving wrinkles, and having high safety.

Below, the anti-inflammatory agent which consists of a bergenin derivative is described.

45 g of the bergenin derivative obtained in Example 2 above, 140 g of lanolin, 140 g of macro gold, 25 g of beeswax and 35 g of ozokerite were added to a clean stainless steel dissolution tank and dissolved at 38 ° C. for 1 hour. This was supplied to a kneader and mixed. This was dissolved again in a dissolution tank, heated, and deaerated with a deaerator to obtain the desired anti-inflammatory agent as an ointment.

As a control, a control sample using lanolin instead of the bergenin derivative obtained in Example 2 was prepared, and used as a control sample in the test.

Below, the test example using Example 2 is demonstrated.
(Test Example 5)
Nineteen females who are mushrooms and honeyworms due to house dust mites aged 20-69 years old, 1 g of the anti-inflammatory agent obtained in Example 9 once a day, outside the nasal cavity, around the nasal cavity and around the oral cavity for 14 days It was applied to.

The reactivity of house dust mites was observed before application and on the 14th day of application. Further, blood was collected before application and on the 14th day of application, and the amount of TNF alpha and IgE were measured by an immunoantibody method.

As a result, after application, the number of mite and honeyworms due to house dust mites was 37% on average compared to before application, and in both cases, a decrease in reactivity to pollen was observed. The average amount of TNF alpha in the blood was 38% compared to that before application, and a decrease in the amount of TNF alpha, an inflammatory cytokine, was observed.

The blood IgE amount was 40% of the value before application, and a decrease in the IgE amount was observed. In addition, no abnormalities were observed in the physical condition, health condition, and laboratory test values after application.

Therefore, the anti-inflammatory agent comprising the bergenin derivative of Example 9 reduced the amount of inflammatory cytokines and IgE against hay fever, exhibited an anti-inflammatory effect, and was confirmed to be safe.

On the other hand, when a control sample using lanolin was used in place of the bergenin derivative, the number of expression of scabs and hanamids by cedar pollen was 100% on average compared to before application, and the reactivity to pollen changed. There was no.

In addition, the amount of TNF alpha in blood after using a control sample using lanolin is 99% on average compared to before application, and the amount of TNF alpha, which is an inflammatory cytokine, does not change compared to before use. It was.

Furthermore, the amount of IgE in blood after using a control sample using lanolin was 102% on average, and no change was observed compared to before use.

The bergenin derivative having an inhibitory action on the production of inflammatory cytokines according to the present invention exhibits an excellent function with weak side effects for the purpose of preventing and improving systemic and local inflammation, and has various effects such as dermatitis, pneumonia, bronchitis and hepatitis. It improves the QOL of patients suffering from inflammation or semi-healthy people.

In addition, the food preparation comprising a bergenin derivative having an inhibitory action on the production of inflammatory cytokines according to the present invention can improve or develop inflammation such as hay fever, house dust mite, sick house syndrome, cold, metabolic syndrome, allergy, dermatitis, etc. It contributes to the improvement of the quality of people's lives.

Furthermore, a cosmetic product comprising a bergenin derivative having an inhibitory action on the production of inflammatory cytokines has an effect of improving or preventing wrinkles and dullness caused by sunburn, inflammation such as skin inflammation and atopy, and improves the QOL of the public. .

In addition, according to the anti-inflammatory agent comprising a bergenin derivative having an inhibitory action on inflammatory cytokine production, it contributes to the improvement or prevention of inflammation such as dermatitis, hepatitis, encephalitis, pneumonia, cold, pancreatitis, hay fever, allergy, Improve national life. This anti-inflammatory agent has few side effects and contributes to the activation of the medical and pharmaceutical industries by exhibiting an excellent anti-inflammatory action.

The head and internal organs of Yukinoshita or Akamegashiwa and edible fish are treated as waste. The present invention reduces waste from the point of effectively using these wastes, can prevent environmental destruction due to soil and marine eutrophication due to waste, and is expected to effectively use fishery and agricultural resources, Furthermore, it contributes to the development of fisheries, agriculture and related industries.

Claims (9)

A bergenin derivative represented by the following formula (1) having an inhibitory action on inflammatory cytokine production.

X is either hydrogen or a methyl group.
Y is either hydrogen or a methyl group.
Z is any one selected from palmitic acid, gallic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, and stearic acid. A palmitic acid and a transesterified lipase are added to a pulverized leaf or flower of Yukinoshita or Akamegashiwa, heated, and extracted with vegetable oil. X in the bergenin derivative according to claim 1, wherein X is a methyl group, Y Is a bergenin derivative represented by the following formula (2) having a suppressive action on inflammatory cytokine production, wherein Z is hydrogen and Z is palmitic acid.

A pulverized leaf or flower of Yukishinoshita or Akamegashiwa is obtained by adding gallic acid and lipase for transesterification, heating and extracting with vegetable oil, wherein in the bergenin derivative according to claim 1, X is a methyl group, Y Is a bergenin derivative represented by the following formula (3) having an inhibitory action on inflammatory cytokine production, wherein Z is hydrogen and Z is gallic acid

It is obtained by adding eicosapentaenoic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating, extracting with vegetable oil, X of the bergenin derivative according to claim 1, wherein X is a methyl group, A bergenin derivative represented by the following formula (4) having an inhibitory action on inflammatory cytokine production, wherein Y is hydrogen and Z is eicosapentaenoic acid.

It is obtained by adding docosahexaenoic acid and lipase for transesterification to the ground leaves or flowers of Yukinoshita or Akamegashiwa, heating, extracting with vegetable oil, and among the bergenin derivatives according to claim 1, X is a methyl group, Y Is a bergenin derivative represented by the following formula (5) having a suppressive action on inflammatory cytokine production, wherein Z is docosahexaenoic acid

The bergenin derivative having an inflammatory cytokine production inhibitory effect according to claim 1, obtained by extracting a fermented product obtained by adding fermented natto to fermented fish, saxifrage or red wrinkle leaves or flowers and soybeans with a vegetable oil. Claim 1 or Claim 2 or Claim 3 or Claim 4 or Claim 5 or Claim 6 with 1 weight of the bergenin derivative having an inhibitory action on inflammatory cytokine production, chrysanthemum flower extract-containing vegetable oil 0.01 to A food preparation comprising a composition containing 0.5 wt., Pine needle extract-containing vegetable oil 0.01-0.5 wt. Claim 1 or Claim 2 or Claim 3 or Claim 4 or Claim 5 or Claim 6 with 1 weight of bergenin derivative having an inhibitory action on inflammatory cytokine production, chrysanthemum flower extract-containing vegetable oil 0.05 to A cosmetic comprising a composition containing 0.8% by weight of a pine leaf extract-containing vegetable oil of 0.05 to 0.8%. An anti-inflammatory agent comprising the bergenin derivative having an inhibitory action on inflammatory cytokine production according to claim 1, claim 2, claim 3, claim 4, claim 5, or claim 6.