JP2007204444A - Pinocembrin chalcone derivative having inhibiting action on production of inflammatory cytokine, food preparation, cosmetic, and anti-inflammatory agent each comprising the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pinocembrin chalcone derivative having a weak side effect and an excellent inhibiting action on production of an inflammatory cytokine, a food preparation, a cosmetic, and an anti-inflammatory agent each comprising the same. <P>SOLUTION: The pinocembrin chalcone derivative having a weak side effect and an excellent inhibiting action on production of inflammatory cytokine is a derivative formed by bonding pinocembrin chalcone to a compound selected from among palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, α-lipoic acid, γ-linolenic acid, stearic acid, and methylstearic acid, and is obtained by admixing crushed leaves of a pine or green tea, lipase for transesterification, and one of the above compound, heating the admixture, and extracting it therefrom with soybean oil containing an essence of persimmon leaves, or by fermenting the mixture with soybeans, and Bacillus natto, and extracting it therefrom with soybean oil containing an essence of persimmon leaves. The food preparation or the cosmetics comprises the pinocembrin chalcone derivative, astaxanthin, and soybean oil containing an essence of persimmon leaves. The anti-inflammatory agent comprises the pinocembrin chalcone derivative. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

The present invention relates to a pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production. The present invention also relates to a food preparation, a cosmetic and an anti-inflammatory agent comprising a composition containing the pinocembrin chalcone derivative, astaxanthin and soybean leaf extract-containing soybean oil.

Inflammatory cytokines are 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).

On the other hand, steroid hormone preparations include clobetasol propionate, diflorazone acetate, prezonidolone, cortisone, etc., but as side effects, immune function decline, opportunistic infection, adrenal function decline, dermatitis such as steroid purpura, etc. are known (for example, Non-patent document 4).

As a result, steroid hormone preparations have the disadvantage that they cannot be used for a long time.

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, there is a drawback that its function is mild. Useful naturally derived plant materials are used as pharmaceuticals, foods, cosmetics, etc., among them, the pinus densiflora, which is the leaf of the scientific name Pinus densiflora, contains stilbene derivatives, flavonoids and chalcones, Although a strong antibacterial action is known (see, for example, Non-Patent Document 6), there is no report on their anti-inflammatory action.

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 pinocembrin chalcone that suppresses inflammatory cytokine production.
Japanese Patent No. 3377529 JP 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 .; Et al., Pathology, 70, 229-236, 2002-2003. Price, C.I. T.A. Et al., Appl. Environ. Microbiol, 68, 5417-5421, 2002.

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.

Further, ordinary chalcones 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 pinocembrin chalcone derivative having weak side effects and having an excellent inflammatory cytokine production inhibitory effect.

Moreover, it is obtained by adding palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid or docosahexaenoic acid and lipase for transesterification to the pulverized product of Matsuba or green tea, heating and extracting with soybean oil containing bamboo leaf extract. An object of the present invention is to provide a pinocembrin chalcone derivative having weak side effects and having an excellent inhibitory effect on the production of inflammatory cytokines.

Pinocemblies with excellent inflammatory cytokine production-suppressing effects and low side effects obtained by extracting fermented products such as edible fish, pine or green tea and soybeans with fermented natto bacteria and soybean oil containing koji leaf extract It is to provide a n-chalcone derivative.

Furthermore, from a composition containing 0.01 to 0.5 weight of astaxanthin and 0.01 to 0.5 weight of soybean leaf extract-containing soybean oil in 1 weight of a pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production It is to provide an excellent food preparation with weak side effects.

In addition, a composition containing 0.006 to 0.4 weight of astaxanthin and 0.05 to 0.8 weight of soybean oil containing persimmon leaf extract in 1 weight of a pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production Is to provide cosmetics consisting of

Another object of the present invention is to provide an anti-inflammatory agent comprising a pinocembrin chalcone 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 pinocembrin chalcone derivative represented by the following formula (1) having an inhibitory action on inflammatory cytokine production.

X is any one selected from palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, and methyl stearic acid.

The invention described in claim 2 is obtained by adding palmitic acid and lipase for transesterification to a ground product of pine or green tea, heating and extracting with soybean oil containing persimmon leaf extract. Among these pinocembrin chalcone derivatives, the present invention relates to a pinocembrin chalcone derivative represented by the following formula (2) having an inhibitory action on inflammatory cytokine production, wherein X is palmitic acid.

The invention according to claim 3 is obtained by adding 14-methyl palmitic acid and lipase for transesterification to a ground product of pine or green tea, heating and extracting with soybean oil containing persimmon leaf extract, 1. The pinocembrin chalcone derivative represented by the following formula (3) having an inhibitory action on inflammatory cytokine production, wherein X is 14-methylpalmitic acid among the pinocembrin chalcone derivatives described in 1.

The invention according to claim 4 is obtained by adding eicosapentaenoic acid and lipase for transesterification to a ground product of pine or green tea, heating and extracting with soybean oil containing persimmon leaf extract. Among the described pinocembrin chalcone derivatives, the present invention relates to a pinocembrin chalcone derivative represented by the following formula (4) having an inhibitory action on inflammatory cytokine production, wherein X is eicosapentaenoic acid.

The invention according to claim 5 is obtained by adding docosahexaenoic acid and lipase for transesterification to a ground product of pine or green tea, heating and extracting with soybean oil containing persimmon leaf extract. Among the pinocembrin chalcone derivatives of the above, it relates to a pinocembrin chalcone derivative represented by the following formula (5) having an inflammatory cytokine production inhibitory action in which X is docosahexaenoic acid.

The invention according to claim 6 is an inflammation according to claim 1, which is obtained by extracting a fermented product obtained by adding natto bacteria to edible fish, pine or green tea and soybean and fermenting it with soybean oil containing koji leaf extract. The present invention relates to a pinocembrin chalcone derivative having an inhibitory effect on sex cytokine production.

The invention according to claim 7 is the weight of the pinocembrin chalcone derivative having the inflammatory cytokine production inhibitory effect according to claim 1 or claim 2 or claim 3 or claim 4 or claim 5 or claim 6. In addition, the present invention relates to a food preparation comprising a composition containing 0.01 to 0.5 weight of astaxanthin and 0.01 to 0.5 weight of soybean oil extract-containing soybean oil.

The invention according to claim 8 is the weight of the pinocembrin chalcone derivative having an inhibitory action on the production of inflammatory cytokine according to claim 1 or claim 2 or claim 3 or claim 4 or claim 5 or claim 6. In addition, the present invention relates to a cosmetic comprising a composition containing 0.006 to 0.4 weight of astaxanthin and 0.05 to 0.8 weight of soybean oil-containing soybean oil.

The invention according to claim 9 comprises the pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production according to claim 1 or claim 2 or claim 3 or claim 4 or claim 5 or claim 6. It relates to anti-inflammatory agents.

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

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

An inflammatory cytokine in which X is palmitic acid, which is obtained by adding palmitic acid and lipase for transesterification to the pulverized product of beef or green tea according to claim 2, heating, and extracting with soybean oil containing persimmon leaf extract According to the pinocembrin chalcone derivative having a production inhibitory action, side effects are weak and an excellent anti-inflammatory action is exhibited.

X is 14-methylpalmitin obtained by adding 14-methylpalmitic acid and lipase for transesterification to the pulverized product of Matsuba or green tea according to claim 3, heating, and extracting with soybean oil containing persimmon leaf extract. According to the pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production, which is an acid, side effects are weak and an excellent anti-inflammatory action is exhibited.

Inflammation in which X obtained by adding eicosapentaenoic acid and lipase for transesterification to the pulverized bean or green tea according to claim 4, heating and extracting with soybean oil containing persimmon leaf extract is eicosapentaenoic acid According to the pinocembrin chalcone derivative having an action to suppress the production of sex cytokines, side effects are weak and an excellent anti-inflammatory action is exhibited.

An inflammatory cytokine in which X is docosahexaenoic acid obtained by adding docosahexaenoic acid and lipase for transesterification to the pulverized product of pine or green tea according to claim 5, heating, and extracting with soybean oil containing persimmon leaf extract According to the pinocembrin chalcone derivative having a production inhibitory action, side effects are weak and an excellent anti-inflammatory action is exhibited.

The pino assembly which has an inflammatory cytokine production inhibitory effect obtained by extracting the fermented material which added the fermented natto to fermented fish, pine or green tea, and soybean with fermented soybean oil containing soybean extract According to the nchalcone derivative, side effects are weak and an excellent anti-inflammatory action is exhibited.

The pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production according to claim 7 contains 0.01 to 0.5 weight of astaxanthin and 0.01 to 0.5 weight of soybean leaf extract-containing soybean oil. According to the food preparation comprising the composition, the side effects are weak and an excellent anti-inflammatory action is exhibited.

A weight of pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production according to claim 8, containing 0.006 to 0.4 weight of astaxanthin and 0.05 to 0.8 weight of soybean oil containing bamboo leaf extract According to the cosmetic comprising the composition, the side effects are weak and an excellent wrinkle improving action is exhibited.

According to the anti-inflammatory agent comprising the pinocembrin chalcone derivative having an inhibitory action on the production of inflammatory cytokine according to claim 9, the 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, the pinocembrin chalcone derivative represented by the following formula (1) having an inhibitory action on inflammatory cytokine production will be described.

X is any one selected from palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, and methyl stearic acid.

Originally, pinocembrin chalcone is a derivative of cinnamic acid that is biosynthesized in plants using phenylalanine as a raw material. It is a compound produced from cinnamoyl CoA by chalcone synthase, and the 8-position is hydrogen.

The pinocembrin chalcone derivative here refers to palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid instead of hydrogen at the 8-position of pinocembrin chalcone, as shown in formula (1). , Docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, and methyl stearic acid.

This pinocembrin chalcone derivative is made of any of the substances palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, and methyl stearic acid. The carbon moiety furthest away from the carboxylic acid group is covalently bonded.

This pinocembrin chalcone is present in Matsuba or green tea. It is widely distributed in leaves such as Pinus densiflora pine, green tea, stalks and leaves of plants such as baccaris, and also has a ketone body rich in reactivity at the 7th position, which is also contained in propolis. Although it exhibits an antioxidant action and an antibacterial action, it has a drawback that the structure of pinocembrin chalcone is unstable.

On the other hand, the pinocembrin chalcone derivative mentioned here binds palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearic acid. By doing so, the structure of pinocembrin chalcone is stabilized.

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

The pinocembrin chalcone 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. Suppresses the production of

The pinocembrin chalcone derivatives are palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearic acid, which have high fat-soluble characteristics. Since any one selected from acids is bonded, it has a feature that it can be easily adapted to and absorbed by the cell membranes of the small intestine and skin.

When the pinocembrin chalcone derivative is excessively ingested and absorbed, the excessive amount is decomposed by the esterase in the blood, and the pinocembrin chalcone and the respective palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, Since it is decomposed into docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, and methyl stearic acid, each has been confirmed to be safe, the pinocembrin chalcone derivative is also High safety.

Among the above-mentioned pinocembrin chalcone derivatives, when X is palmitic acid, the saturated fatty acid residue of palmitic acid penetrates into the cell membrane, is easily absorbed into the cell, is easy to act on the target protein kinase C, and has an anti-inflammatory effect. Is preferred because it is enhanced.

Among the above-mentioned pinocembrin chalcone derivatives, when X is 14-methylpalmitic acid, the saturated fatty acid residue of 14-methylpalmitic acid penetrates the cell membrane and is easily absorbed into the cell, and thus becomes a target protein kinase C. It is preferable because it is easy to work and the anti-inflammatory action is enhanced.

Among the above-mentioned pinocembrin chalcone derivatives, when X is eicosapentaenoic acid, an unsaturated fatty acid residue of eicosapentaenoic acid exhibits an inhibitory action on inflammatory prostaglandin production, so that an inflammatory prostaglandin produced from arachidonic acid This is preferable because the anti-inflammatory action is enhanced.

Among the above-mentioned pinocembrin chalcone derivatives, when X is docosahexaenoic acid, the unsaturated fatty acid residue of docosahexaenoic acid exhibits platelet aggregation inhibition and arterial dilation action, thereby improving blood flow and enhancing anti-inflammatory action. Is preferable.

Among the above-mentioned pinocembrin chalcone derivatives, when X is docosapentaenoic acid, the unsaturated fatty acid residue of docosapentaenoic acid exhibits the action of capillary vasodilation, which improves blood flow in the local area of inflammation and inflammation. It is preferable because the substance is excreted and the anti-inflammatory action is enhanced.

Among the above-mentioned pinocembrin chalcone derivatives, when X 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. preferable.

Among the above-mentioned pinocembrin chalcone derivatives, when X is alpha-lipoic acid, the SH group of alpha-lipoic acid exhibits an antioxidative action, and the tissue damage against oxidative stress is protected and the anti-inflammatory action is enhanced. Is preferable.

Among the above-mentioned pinocembrin chalcone derivatives, when X is stearic acid, the saturated fatty acid residue of stearic acid penetrates into the cell membrane, is easily absorbed into the cell, is easy to act on the target protein kinase C, and has anti-inflammatory action Is preferred because it is enhanced.

Among the pinocembrin chalcone derivatives described above, when X is methyl stearic acid, saturated fatty acid residues of methyl stearic acid penetrate into the cell membrane, are easily absorbed into the cell, are easy to work on the target protein kinase C, This is preferable because the inflammatory action is enhanced.

In addition, it is preferable to extract and purify pinocembrin chalcone from Matsuba or green tea because it is easy to purify. Furthermore, it is preferable to purify the fatty acid from fish oil or fish and to use the purified fish oil-derived fatty acid.

For example, these fatty acids can be obtained from Nissui Pharmaceutical, Nissui Fishery, and Toyo Fisheries, and can be biosynthesized or chemically synthesized using enzymes.

When a pinocembrin chalcone derivative is obtained from these raw materials by 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, Neulase F3G or the like is used. In addition, in the case of chemical synthesis reaction, it is heated together with a metal catalyst such as magnesium or aluminum.

These raw materials are put in a reaction tank and a reaction is performed together with a solvent. In addition, it is preferable that the reaction product is obtained as a crude product by removing the solvent because the cost required for purification can be reduced.

The target pinocembrin chalcone derivative can be obtained by extraction from a natural material or purification. Natural materials include plants such as pine or green tea, seaweed, mushrooms, food animals, food fish, molluscs, insects, crustaceans and the like. In particular, the heads of pine, edible fish, and eels have a high content and are therefore easy to extract.

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 pinocembrin chalcone derivative by fermentation using microorganisms or yeast, since it has been confirmed to be safe for food and has abundant food experience. In this case, the microorganisms used are natto and lactic acid bacteria. There are bean yeast and Bacillus subtilis, and yeast includes beer yeast and alcoholic yeast, and natto is particularly preferable because of its excellent transesterification.

The fermentation is carried out using a fermentation tank by adding the microorganism or yeast to a fermentation base such as matsuba or green tea, fish, fish head or internal organs, soybean or milk. After the fermentation, the desired pinocembrin chalcone derivative can be obtained from a mixture of microorganisms or yeast and fermentation broth.

Among these, the head and internal organs of pine or green tea and eel are preferred because they have abundant food experience and can stably supply the target pinocembrin chalcone derivative.

Furthermore, when separating the target pinocembrin chalcone derivative from the fermented product from the fermented product, it is obtained by collecting an oil-soluble portion that is extracted and separated using a soybean leaf extract-containing soybean oil, This is preferable because the substance is stabilized by the antioxidant power of the soybean leaf extract-containing soybean oil and a high-quality derivative is separated.

When extracted from plants, Pinus densiflora red pine pine, scientific name Pine sylvestis pine pine, black pine pine, green tea, ginseng garlic, onion, garlic, soybeans, gypsophila, licorice, bark, Flower, capsicum, oyster, pear, chestnut, green tea, cod, wasabi, bracken, rice, wheat, corn, radish, rape blossom, cherry, pine, aoki, akane, akamegashiwa, akebi, amachazuru, amadokoro, aloe, licorice, itadori, Wild boar, Dwarf cricket, Ukogi, Nepenthes, Udo, Ume, Vulture, Shrimp, Auren, Psyllium, Ochera, Okra, Hypericum, Onamomi, Ominae, Oyster, Japanese calligraphy, Kara Susikaku, Kawaraketsumei, Kawaranadeshiko, Kannaoi, Kikumo, Kyo-Kou, Kisame-ges, Ki-hada, Kiran-so, Kinshi-hihiki, Kakuiso, Kuboke, Kudzu, Gardenia, Kouhone, Kobushi, Sai-kachi, Sabon-shirai-bira Assembly, Tamshiba, Taranoki, Dandelion, Chigaya, Tsuruganeninjin, Tsuwabuki, Dokudami, Tochinoki, Tochibaninjin, Nanten, Japanese rose, chickweed, pearl barley, boxweed, chickweed, Hishi, Hitotsuba, Biwa, Fuki, Fukushimata Yukinoshita, mugwort, gentian, forsythia, wintersweet, leaf, flower or root are preferred because they are readily available.

As the plants to be extracted, the pine genus Pinus, Low Grow, Maurice Arboretum witches bloom, Janome red pine, Weeping pine, Tanyousho, Taikosho, Kuromatsu, Angelica's Thunderhead, Arakawasho, Bandaisho, Benikujakumatsu, Peacock , Western pine, janome black pine, bigon black pine, big bear air, thunder head, trough pine, yellow pine black pine, igagoyo, bartle corn pine, alman pine, alman pine, chug pine, bank pine, jack pine, bank shear pine, girard sweeper, scoop White pine, Sun pine, White pine, Hakshaw, Junes bloom, Silver ghost, Canary pine, European pine Chinese pine, chalet, chamois, compact taglauca, nana, silver scene, lodgepole pine, white pine, cool terri, big corn pine, echina pine, echina-pine, short leaf pine, flexi pine, flexi pine, ex trouble, van der wolf spramide, hakkouda Aleppo pine, Bosnia pine, Korean pine, Korean pine, Beni pine, Glauca, Jack corbit, Oculus draconis, Silver Valley, Montezuma pine, Row Glow, Morris Arboretum witches bloom, Janome red pine, Fern pine, Chinese pine Goyo, white pine, montana pine, swiss pine, swiss Miyamatsu, aurea, big Na, green candle, honeycomb, mitch mini, mops, prostrata, sherwood compact, white bud, winter gold, mug pine, pumilio, rostrata, bishop pine, european black pine, black pine, austrian pine, bobby mcregger, gold fingers, helena , Helga, Honiburkkiana, Jedero, Moselli, Daiosho, Daiomatsu, Goyomatsu, Himekomatsu, Aoigoyoyo, Aoi, Emperor, Fukuzumi, Grauca, Janomegoyo, Negigoyo, Tempelhofu, Yasubusago, Matsumitsu Matsu, , Macedonian pine, French cabbage show, Cagan show, French caliper, Italian pine, sill Barcrest, Parasol Pine, Ponderosa Pine, High Pine, Siberian Pine, Prostrata, Jesus Alpine, Radiata Pine, Monterey Pine, Radiata Pine, Resinosa Pine, Red Pine, Rigida Pine, American Honey Pine, Honey Pine, Sherman Eddy, Strobe Pine, Blue Shag, Compactor, Coney Island, Fastigearata, Globosa, Golden Candles, Greg, Macopin, Merrimack, Minuta, Nana, Paul Waxman, Pendura, Radiata, Sea Archin, Yukon, Ambracurifera, Uncatena, Felucades Bloom, Europe Red pine, Scots pine, Russian red pine, Alvins, Andorra, Argentea compactor, Aurea, Beauvronensi , Fastigitata, Girard pyramide, Kurobosanana, Globosaviridis, Hillside Creeper, Little Burari, Mitchweeping, Moselli, Nana, Nana Compactor, Repens, Chugokukamatsu, Taburi Formis, Teidamatsu, Taedamatsu, Frankincense pine, Black Pine, Otokomatsu , Leaves, bark and berries of pine, virginia pine, cedar pine, and bhutan pine are used.

Among these, red pine leaves are preferable because they extract the target pinocembrin chalcone derivative and are discarded as natural waste, and can reduce waste and prevent environmental pollution.

When extracting from green tea, the leaves, stems or roots of Japanese green tea, powdered tea, and Chinese Assam green tea are preferred because they are readily available. The green tea here is typically the scientific name Camellia sinensis and includes all green tea belonging to the genus Camellia.

Moreover, it is preferable to utilize purification operations, such as resin for isolation | separation, for isolation | separation of the target pinocembrin chalcone derivative. In the case of separation, by using the soybean leaf extract-containing soybean oil in the crude purification stage, the antioxidant effect of the bamboo leaf extract is exhibited and the target derivative is stably maintained.

It is preferable to purify the target pinocembrin chalcone derivative from the reaction product or composition from the viewpoint that the intake can be reduced 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 preferred. 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 XAD-2 or XAD-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 dissolved 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 the collection, it is preferable to remove the solvent by drying or vacuum drying to obtain the target pinocembrin chalcone derivative as a powder or a concentrated liquid because the influence of the solvent can be excluded. The pinocembrin chalcone derivative is obtained as a liquid or powder. The obtained pinocembrin chalcone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools 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.

The above-mentioned food preparation is used for the purpose of anti-inflammation, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, nutrition tonic, maintenance of liver function, and the like.

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. Sanitary tools are used for gauze, masks, pollen countermeasure masks, sanitary products, and the like. In addition, this cosmetic exhibits an excellent therapeutic or preventive action against atopic dermatitis in which a large amount of inflammatory cytokines are produced.

Next, the pinocembrin represented by the above formula (1) obtained by adding palmitic acid and lipase for transesterification to the pulverized product of Matsuba or green tea, heating and extracting with soybean oil containing persimmon leaf extract Of the chalcone derivatives, a pinocembrin chalcone derivative represented by the following formula (2) having an inhibitory action on inflammatory cytokine production in which X is palmitic acid will be described.

The pinocembrin chalcone derivative mentioned here is the above-mentioned pinocembrin chalcone derivative, which is a derivative in which the carbon farthest from the carboxylic acid of palmitic acid is covalently bonded to the 8-position of the pinocembrin chalcone.

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

The pinocembrin chalcone 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. The factor suppresses the gene level expression of inflammatory cytokines and suppresses the production of inflammatory cytokines. Further, in the above-mentioned pinocembrin chalcone derivative, the 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 the anti-inflammatory action is enhanced. preferable.

The pinocembrin chalcone derivative is obtained by adding palmitic acid and lipase for transesterification to a ground product of pine or green tea, heating the mixture, and extracting it with soybean oil containing bamboo leaf extract.

The pine tree is red pine, wax-grow, morris arboretum witches bloom, jano red pine, weeping pine, tanyo show, tagyosho, black pine leaves. Is abundant and safety has been confirmed. Green tea from Japan and China is used. The green tea here is typically the scientific name Camellia sinensis and includes all green tea belonging to the genus Camellia.

In addition, it is also used as a raw material for cosmetics in the form of Matsuba extract or green tea leaves. The pine trees used here are those that have been naturally bred or cultivated in Asia such as Japan, South Korea, China and Taiwan, North America, South America, Oceania and Africa. Chinese products are preferred because they can track the use history of pesticides, are stable in quality, and inexpensive.

Matsuba or green tea may be either fresh or dried.

The collected pine or green tea is preferably washed with tap water.

Matsuba or green tea is 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 palmitic acid used here is preferably extracted from a plant such as rapeseed, sesame or the like such as fish, Ryoshoku, Fuji Oil Co., Ltd.

The transesterification lipase used here is, for example, a lipozyme or novozyme 435 manufactured by Novozyme, a lipase PL or lipase QLM manufactured by Meisei 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, etc., the above-mentioned crushed product of Matsuba or green tea, palmitic 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 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 crushed product of pine or green tea to be added.

As said temperature of heating, 10-30 degreeC is preferable and 13-27 degreeC is more preferable.

The heating time is preferably 1 to 24 hours, more preferably 2 to 14 hours.

The heating is preferably performed while stirring, and a rate of 8 to 120 times per minute is preferable.

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

The reaction product is separated by the soybean leaf extract-containing soybean oil. Since the reaction product has high oil solubility, it is dissolved in soybean leaf extract-containing soybean oil.

Bamboo leaf extract-containing soybean oil is an oil-soluble polyphenol that contains oil-soluble polyphenols extracted by adding soybean oil to the pulverized bamboo leaf, and has a stable target derivative. Can be separated.

The bamboo leaf used in the soybean leaf extract-containing soybean oil can be used in any of Japan, China, and Taiwan.

A bamboo leaf cultivated without using a pesticide is preferable because it can avoid the danger caused by the pesticide.

The amount of soybean oil extract-containing soybean oil to be added is preferably 0.4 to 3 wt.

After the isolated pinocembrin chalcone derivative is absorbed into the body, the excess amount is decomposed by esterase and further metabolized in the liver, so that it is highly safe and has few side effects.

Separating and purifying the target pinocembrin chalcone 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 a separation resin.

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 to separate and purify with a suitable separation solvent and remove the solvent to obtain the desired pinocembrin chalcone derivative.

The pinocembrin chalcone derivative thus obtained is obtained as a liquid or a powder. The obtained pinocembrin chalcone 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 above-mentioned food preparation is used for the purpose of anti-inflammation, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, nutrition tonic, maintenance of liver function, and the like.

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, 14-methylpalmitic acid and lipase for transesterification are added to a pulverized product of Matsuba or green tea, heated, and extracted by soybean oil extract-containing soybean oil. Among the pinocembrin chalcone derivatives, a pinocembrin chalcone derivative represented by the following formula (3) having an inhibitory action on inflammatory cytokine production in which X is 14-methylpalmitic acid will be described.

The pinocembrin chalcone derivative here is the above-mentioned pinocembrin chalcone derivative, which is a derivative in which the carbon farthest from the carboxylic acid of 14-methylpalmitic acid is covalently bonded to the 8-position of the pinocembrin chalcone. .

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

The pinocembrin chalcone 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. The factor suppresses the gene level expression of inflammatory cytokines and suppresses the production of inflammatory cytokines.

This pinocembrin chalcone derivative is preferable because the saturated fatty acid residue of 14-methylpalmitic acid penetrates into the cell membrane, is easily absorbed into the cell, easily acts on the target protein kinase C, and has an enhanced anti-inflammatory effect. .

The pinocembrin chalcone derivative is obtained by adding 14-methylpalmitic acid and lipase for transesterification to a pulverized product of Matsuba or green tea, heating, and extracting with soybean oil containing persimmon leaf extract.

The pine tree is red pine, wax-grow, morris arboretum witches bloom, jano red pine, weeping pine, tanyo show, tagyosho, black pine leaves. Is abundant and safety has been confirmed. As green tea, Japanese green tea Assam green tea is used. The green tea here is typically the scientific name Camellia sinensis and includes all green tea belonging to the genus Camellia.

In addition, it is also used as a raw material for cosmetics in the form of Matsuba extract or green tea leaves.

The pine used here can be any naturally bred or cultivated pine in Asia such as Japan, Korea, China and Taiwan, 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.

Matsuba or green tea may be either fresh or dried.

The collected pine or green tea is preferably washed with tap water.

Matsuba or green tea is 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 14-methyl palmitic acid used here is preferable because it is extracted and purified from fish from Ryoshoku, Oriza Yuka Co., Ltd., Fuji Oil Co., Ltd., sesame seeds, rapeseed, walnuts, etc. .

The transesterification lipase used here is a transesterification lipase, for example, Lipozyme or Novozyme 435 manufactured by Novozyme, Lipase PL or Lipase QLM manufactured by Meisho Sangyo Co., Ltd., Lipase AY “Amano” manufactured by Amano Enzyme. 30G, lipase G “Amano” 50, lipase F-AP15, neurase F3G and the like are high in quality, and these are preferable because of high safety.

To a clean stainless steel cylinder, etc., the above-mentioned crushed product of Matsuba or green tea, 14-methylpalmitic 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 14-methyl palmitic acid is preferably 0.02 to 0.5 weight, and the amount of lipase for transesterification is preferably 0.0001 to 0.04 weight with respect to 1 weight of the pulverized product of Matsuba or green tea to be added.

As said temperature of heating, 10-30 degreeC is preferable and 13-27 degreeC is more preferable.

The heating time is preferably 1 to 24 hours, more preferably 2 to 14 hours.

The heating is preferably performed while stirring, and a rate of 8 to 120 times per minute is preferable.

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

The reaction product is separated by the soybean leaf extract-containing soybean oil. Since the reaction product has high oil solubility, it is dissolved in soybean leaf extract-containing soybean oil.

Bamboo leaf extract-containing soybean oil is an oil-soluble polyphenol that contains oil-soluble polyphenols extracted by adding soybean oil to the pulverized bamboo leaves, and protects the target derivative from oxidation. In addition, the structure can be stably maintained.

The bamboo leaf used in the soybean leaf extract-containing soybean oil can be used in any of Japan, China, and Taiwan.

A bamboo leaf cultivated without using a pesticide is used, which is preferable because the danger caused by the pesticide can be avoided.

0.4 to 3 weights of soybean oil extract-containing soybean oil to be added is preferable with respect to 1 weight of pulverized products of pine or green tea to be added.

After the isolated pinocembrin chalcone derivative is absorbed into the body, the excess amount is decomposed by esterase and further metabolized in the liver, so that it is highly safe and has few side effects.

Separating and purifying the target pinocembrin chalcone 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 a separation resin.

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 to separate and purify with a suitable separation solvent and remove the solvent to obtain the desired pinocembrin chalcone derivative.

The pinocembrin chalcone derivative thus obtained is obtained as a liquid or a powder. The obtained pinocembrin chalcone 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 above-mentioned food preparation is used for the purpose of anti-inflammation, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, nutrition tonic, maintenance of liver function, and the like.

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, eicosapentaenoic acid and lipase for transesterification are added to the pulverized product of Matsuba or green tea, heated, and extracted with soybean leaf extract-containing soybean oil. The pino assembly represented by the above formula (1) is obtained. The pinocembrin chalcone derivative represented by the following formula (4) having an inhibitory action on inflammatory cytokine production, wherein X is eicosapentaenoic acid, among the nchalcone derivatives will be described.

The pinocembrin chalcone derivative mentioned here is the above-mentioned pinocembrin chalcone derivative, which is a derivative in which the carbon farthest from the carboxylic acid of eicosapentaenoic acid is covalently bonded to the 8-position of the pinocembrin chalcone.

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

The pinocembrin chalcone 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. The factor suppresses the gene level expression of inflammatory cytokines and suppresses the production of inflammatory cytokines.

The above-mentioned pinocembrin chalcone derivative reduces the amount of inflammatory prostaglandins produced from arachidonic acid, because the unsaturated fatty acid residue of eicosapentaenoic acid exhibits inflammatory prostaglandin production inhibitory action, and has anti-inflammatory action Is preferred because it is enhanced.

The pinocembrin chalcone derivative is obtained by adding eicosapentaenoic acid and lipase for transesterification to a pulverized product of Matsuba or green tea, heating, and extracting with soybean oil containing bamboo leaf extract.

The pine tree is red pine, wax-grow, morris arboretum witches bloom, jano red pine, weeping pine, tanyo show, tagyosho, black pine leaves. Is abundant and safety has been confirmed. Green tea from Japan and China and Assam green tea are used. The green tea here is typically the scientific name Camellia sinensis and includes all green tea belonging to the genus Camellia.

In addition, it is also used as a raw material for cosmetics in the form of Matsuba extract or green tea leaves.

The pine used here can be any naturally bred or cultivated pine in Asia such as Japan, Korea, China and Taiwan, 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.

Matsuba or green tea may be either fresh or dried.

The collected pine or green tea is preferably washed with tap water.

Matsuba or green tea is 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 preferable because a product extracted and purified from fish from sardines, mackerel and the like manufactured by Toyo Suisan Co., Ltd. and Nissui Pharmaceutical Co., Ltd. is high in quality and has 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 Meisei 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.

The above-mentioned crushed product of Matsuba or green tea, eicosapentaenoic acid and lipase for transesterification are added to a clean stainless steel cylinder 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 0.13 to 0.8 weight, and the amount of lipase for transesterification is preferably 0.0001 to 0.04 weight with respect to 1 weight of the pulverized product of Matsuba or green tea to be added.

As said temperature of heating, 10-30 degreeC is preferable and 18-25 degreeC is more preferable.

The warming time is preferably 1 to 24 hours, and more preferably 3 to 12 hours.

The heating is preferably performed while stirring, and a rate of 10 to 100 times per minute is preferable.

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

The reaction product is separated by the soybean leaf extract-containing soybean oil. Since the reaction product has high oil solubility, it is dissolved in soybean leaf extract-containing soybean oil.

Bamboo leaf extract-containing soybean oil is an oil-soluble polyphenol that contains oil-soluble polyphenols extracted by adding soybean oil to the pulverized bamboo leaf, and has a stable target derivative. Can be separated.

The bamboo leaf used in the soybean leaf extract-containing soybean oil can be used in any of Japan, China, and Taiwan.

A bamboo leaf cultivated without using a pesticide is preferable because it can avoid the danger caused by the pesticide.

0.4 to 3 weights of soybean oil extract-containing soybean oil to be added is preferable with respect to 1 weight of pulverized products of pine or green tea to be added.

After the isolated pinocembrin chalcone derivative is absorbed into the body, the excess amount is decomposed by esterase and further metabolized in the liver, so that it is highly safe and has few side effects.

Separating and purifying the target pinocembrin chalcone 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 a separation resin.

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 to separate and purify with a suitable separation solvent and remove the solvent to obtain the desired pinocembrin chalcone derivative.

The pinocembrin chalcone derivative thus obtained is obtained as a liquid or a powder. The obtained pinocembrin chalcone 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 above-mentioned food preparation is used for the purpose of anti-inflammation, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, nutrition tonic, maintenance of liver function, and the like.

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, pinocembrin represented by the above formula (1) obtained by adding docosahexaenoic acid and lipase for transesterification to the pulverized product of Matsuba or green tea, heating and extracting with soybean oil containing persimmon leaf extract Of the chalcone derivatives, a pinocembrin chalcone derivative represented by the following formula (5) having an inhibitory action on inflammatory cytokine production in which X is docosahexaenoic acid will be described.

The pinocembrin chalcone derivative mentioned here is the above-mentioned pinocembrin chalcone derivative, which is a derivative in which the carbon farthest from the carboxylic acid of docosahexaenoic acid is covalently bonded to the 8-position of the pinocembrin chalcone.

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

The pinocembrin chalcone 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. The factor suppresses the gene level expression of inflammatory cytokines and suppresses the production of inflammatory cytokines.

The above-described pinocembrin chalcone derivative is preferable because the unsaturated fatty acid residue of docosahexaenoic acid exhibits platelet aggregation inhibition and arterial dilation effects, thereby improving blood flow and enhancing anti-inflammatory activity.

The above-mentioned pinocembrin chalcone derivative is obtained by adding docosahexaenoic acid and lipase for transesterification to pulverized matsuba, heating, and extracting with soybean oil containing bamboo leaf extract.

The pine tree is red pine, wax-grow, morris arboretum witches bloom, jano red pine, weeping pine, tanyo show, tagyosho, black pine leaves. Is abundant and safety has been confirmed. Green tea from Japan and China and Assam tea are used. The green tea here is typically the scientific name Camellia sinensis and includes all green tea belonging to the genus Camellia.

In addition, it is also used as a raw material for cosmetics in the form of Matsuba extract or green tea leaves.

The pine used here can be any naturally bred or cultivated pine in Asia such as Japan, Korea, China and Taiwan, 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.

Matsuba or green tea may be either fresh or dried.

The collected pine or green tea is preferably washed with tap water.

Matsuba or green tea is 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 docosahexaenoic acid used here is extracted and purified from fish such as algae, sardine, mackerel, etc. manufactured by Toyo Suisan Co., Ltd., Nissui Pharmaceutical Co., Ltd., and Nihon Suisan Co., Ltd. These are high quality and low in 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 Meisei 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 crushed pine or green tea, 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 0.23 to 0.8 weight, and the amount of lipase for transesterification is preferably 0.0001 to 0.04 weight with respect to 1 weight of the pulverized product of Matsuba or green tea to be added.

As said temperature of heating, 10-30 degreeC is preferable and 18-25 degreeC is more preferable.

The warming time is preferably 1 to 24 hours, and more preferably 3 to 12 hours.

The heating is preferably performed while stirring, and a rate of 10 to 100 times per minute is preferable.

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

The reaction product is separated by the soybean leaf extract-containing soybean oil. Since the reaction product has high oil solubility, it is dissolved in soybean leaf extract-containing soybean oil.

Bamboo leaf extract-containing soybean oil is an oil-soluble polyphenol that contains oil-soluble polyphenols extracted by adding soybean oil to the pulverized bamboo leaf, and has a stable target derivative. Can be separated.

The bamboo leaf used in the soybean leaf extract-containing soybean oil can be used in any of Japan, China, and Taiwan.

A bamboo leaf cultivated without using a pesticide is preferable because it can avoid the danger caused by the pesticide.

0.4 to 3 weights of soybean oil extract-containing soybean oil to be added is preferable with respect to 1 weight of pulverized products of pine or green tea to be added.

After the isolated pinocembrin chalcone derivative is absorbed into the body, the excess amount is decomposed by esterase and further metabolized in the liver, so that it is highly safe and has few side effects.

Separating and purifying the target pinocembrin chalcone 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 a separation resin.

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 to separate and purify with a suitable separation solvent and remove the solvent to obtain the desired pinocembrin chalcone derivative.

The pinocembrin chalcone derivative thus obtained is obtained as a liquid or a powder. The obtained pinocembrin chalcone 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 above-mentioned food preparation is used for the purpose of anti-inflammation, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, nutrition tonic, maintenance of liver function, and the like.

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 pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production obtained by extracting fermented products obtained by adding fermented natto to fermented fish, pine or green tea and soybeans with soybean oil containing koji leaf extract Will be described.

The pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production here is the above-mentioned pinocembrin chalcone derivative.

That is, instead of hydrogen at position 8 of pinocembrin chalcone, palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearic acid It is a derivative to which any one selected from acids is bound.

This pinocembrin chalcone derivative is made of any of the substances palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, and methyl stearic acid. The carbon moiety furthest away from the carboxylic acid group is covalently bonded.

The pinocembrin chalcone derivative mentioned here is a combination of palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearic acid. Thus, the structure of pinocembrin chalcone is stabilized.

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

The pinocembrin chalcone 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. Suppresses the production of

The pinocembrin chalcone derivatives are palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearic acid, which have high fat-soluble characteristics. Since any one selected from acids is bonded, it has a feature that it can be easily adapted to and absorbed by the cell membranes of the small intestine and skin.

When the pinocembrin chalcone derivative is excessively ingested and absorbed, the excessive amount is decomposed by the esterase in the blood, and the pinocembrin chalcone and the respective palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, Since it is decomposed into docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, and methyl stearic acid, each has been confirmed to be safe, the pinocembrin chalcone derivative is also High safety.

Among the above-mentioned pinocembrin chalcone derivatives, when X is palmitic acid, the saturated fatty acid residue of palmitic acid penetrates into the cell membrane, is easily absorbed into the cell, is easy to act on the target protein kinase C, and has an anti-inflammatory effect. Is preferred because it is enhanced.

Among the above-mentioned pinocembrin chalcone derivatives, when X is 14-methylpalmitic acid, the saturated fatty acid residue of 14-methylpalmitic acid penetrates the cell membrane and is easily absorbed into the cell, and thus becomes a target protein kinase C. It is preferable because it is easy to work and the anti-inflammatory action is enhanced.

Among the above-mentioned pinocembrin chalcone derivatives, when X is eicosapentaenoic acid, an unsaturated fatty acid residue of eicosapentaenoic acid exhibits an inhibitory action on inflammatory prostaglandin production, so that an inflammatory prostaglandin produced from arachidonic acid This is preferable because the anti-inflammatory action is enhanced.

Among the above-mentioned pinocembrin chalcone derivatives, when X is docosahexaenoic acid, the unsaturated fatty acid residue of docosahexaenoic acid exhibits platelet aggregation inhibition and arterial dilation action, thereby improving blood flow and enhancing anti-inflammatory action. Is preferable.

Among the above-mentioned pinocembrin chalcone derivatives, when X is docosapentaenoic acid, the unsaturated fatty acid residue of docosapentaenoic acid exhibits the action of capillary vasodilation, which improves blood flow in the local area of inflammation and inflammation. It is preferable because the substance is excreted and the anti-inflammatory action is enhanced.

Among the above-mentioned pinocembrin chalcone derivatives, when X 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. preferable.

Among the above-mentioned pinocembrin chalcone derivatives, when X is alpha-lipoic acid, the SH group of alpha-lipoic acid exhibits an antioxidative action, and the tissue damage against oxidative stress is protected and the anti-inflammatory action is enhanced. Is preferable.

Among the above-mentioned pinocembrin chalcone derivatives, when X is stearic acid, the saturated fatty acid residue of stearic acid penetrates into the cell membrane, is easily absorbed into the cell, is easy to act on the target protein kinase C, and has anti-inflammatory action Is preferred because it is enhanced.

Among the pinocembrin chalcone derivatives described above, when X is methyl stearic acid, saturated fatty acid residues of methyl stearic acid penetrate into the cell membrane, are easily absorbed into the cell, are easy to work on the target protein kinase C, This is preferable because the inflammatory action is enhanced.

The pinocembrin chalcone derivative is obtained by extracting a fermented product obtained by adding natto bacteria to edible fish, pine or green tea and soybeans and fermenting them with soybean oil containing persimmon leaf extract. As used herein, edible fish refers to fish used for food, and among them, eels have abundant food experience.

Eel head and internal organs have dietary experience, including palmitic acid, 14-methyl palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearic acid Therefore, it is 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 term “pine” refers to the pine genus Pinus, Low Glow, Maurice Arboretum Witches Bloom, Janome Red Pine, Fern Pine, Tanyousho, Taeyeosho, Kuromatsu, Angelica's Thunderhead, Arakawasho, Bandaisha, Benikujak Pine, Peacock, Western Pine, Janome Black Pine, Bigon Black Pine, Big Bear Air, Thunderhead, Trough Pine, Yatsubusa Black Pine, Igagoyo, Burstall Corn Pine, Arman Pine, Alman Pine, Chugoku White Pine, Bank Pine, Jack Pine, Banksia Wiper, Girard Scudick, white pine, white pine, white pine, hakusho, june's bloom, silver ghost, canary pine, europe high Pine, pine pine, chalet, chamois, compact taglauca, nana, silver scene, lodgepole pine, pine pine, cool terri, big corn pine, echina pine, echina pine, short leaf pine, flexi pine, flexi pine, ex trouble, van der wolf spramide, Alaska pine, Aleppo pine, Bosnia pine, Korean pine, Korean pine, Beni pine, Glauca, Jack Corbit, Oculus Draconis, Silver Valley, Montezuma pine, Row Glow, Morris Arboretum witches bloom, Janome red pine, Shida rare pine, Chinese ginger American pokeweed, white pine, montana pine, swiss pine, swiss pine, aurea, bi Gutuna, Green Candle, Honeycomb, Mitch Mini, Mops, Prostrata, Sherwood Compact, White Bud, Winter Gold, Mugs Pine, Pumilio, Rostrata, Bishop Pine, European Black Pine, Scots Black Pine, Austrian Pine, Bobby McGregor, Gold Fingers, Helena , Helga, Honiburkkiana, Jedero, Moselli, Daiosho, Daiomatsu, Goyomatsu, Himekomatsu, Aoigoyoyo, Aoi, Emperor, Fukuzumi, Grauca, Janomegoyo, Negigoyo, Tempelhofu, Yasubusago, Matsumitsu Matsu, , Macedonian pine, French cabbage show, Cagan show, French caliper, Italian pine, Silver Crest, Parasol Pine, Ponderosa Pine, High Pine, Siberian Pine, Prostrata, Jesus Alpine, Radiata Pine, Monterey Pine, Radiata Pine, Resinosa Pine, Red Pine, Rigida Pine, American Honey Pine, Honey Pine, Sherman Eddy, Strobe Pine, Blue Shag, Compactor, Coney Island, Fastigearata, Globosa, Golden Candles, Greg, Macopin, Merrimack, Minuta, Nana, Paul Waxman, Pendura, Radiata, Sea Archin, Yukon, Ambracurifera, Uncatena, Felucades Bloom, Europe Red pine, Scots pine, Russian red pine, Alvins, Andorra, Argentea compactor, Aurea, Beauvrone Sith, Fastigearata, Girard pyramide, Black Bosana, Globosaviridis, Hillside Creeper, Little Burari, Mitchweeping, Moselli, Nana, Nana Compactor, Ripens, Chugokukamatsu, Tabri Formis, Teidamatsu, Taedamatsu, Frankincense Pine, Black Pine, Pine leaves such as Otokomatsu, Omatsu, Virginia pine, Himalayan yoyo, Bhutan pine.

Among these, red pine leaves contain a large amount of the desired pinocembrin chalcone, which is preferable because it is extracted, and is discarded as natural waste, which can reduce waste and prevent environmental pollution. To preferred.

It is preferable to use green tea grown in Shizuoka without any agricultural chemicals. In addition, green tea from Japan or China is used. The green tea here is typically the scientific name Camellia sinensis and includes all green tea belonging to the genus Camellia.

Matsuba or green tea is preferably 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 reaction product is separated by the soybean leaf extract-containing soybean oil. Since the reaction product has high oil solubility, it is dissolved in soybean leaf extract-containing soybean oil.

Bamboo leaf extract-containing soybean oil is an oil-soluble polyphenol that contains oil-soluble polyphenols extracted by adding soybean oil to the pulverized bamboo leaf, and has a stable target derivative. Can be separated.

The bamboo leaf used in the soybean leaf extract-containing soybean oil can be used in any of Japan, China, and Taiwan.

Persimmon leaves cultivated without the use of pesticides are preferred from the viewpoint of avoiding contamination with pesticides.

After the isolated pinocembrin chalcone derivative is absorbed into the body, the excess amount is decomposed by esterase and further metabolized in the liver, so that it is highly safe and has few side effects.

Separating and purifying the target pinocembrin chalcone 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 a separation resin.

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 to separate and purify with a suitable separation solvent and remove the solvent to obtain the desired pinocembrin chalcone derivative.

The pinocembrin chalcone derivative thus obtained is obtained as a liquid or a powder. The obtained pinocembrin chalcone 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 above-mentioned food preparation is used for the purpose of anti-inflammation, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, nutrition tonic, maintenance of liver function, and the like.

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 exhibits an anti-inflammatory action against inflammation caused by sunburn, and is effective for removing 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.

The reaction product is separated by the soybean leaf extract-containing soybean oil. Since the reaction product has high oil solubility, it is dissolved in soybean leaf extract-containing soybean oil.

Bamboo leaf extract-containing soybean oil is an oil-soluble polyphenol that contains oil-soluble polyphenols extracted by adding soybean oil to the pulverized bamboo leaf, and has a stable target derivative. Can be separated.

The bamboo leaf used in the soybean leaf extract-containing soybean oil can be used in any of Japan, China, and Taiwan.

A bamboo leaf cultivated without using a pesticide is preferable because it can avoid the danger caused by the pesticide.

As for each addition amount regarding the said fermentation, 0.03-0.3 weight is preferable for Matsuba or green tea with respect to 1 weight of edible fish, 0.1-3 weight is preferable for soybean, and 0.001-0.1 for Bacillus natto. 0.03 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 30-40 degreeC, and fermentation is performed for 24-72 hours. After fermentation, in order to carry out the extraction efficiently, it is diluted with tap water.

Furthermore, the fermented product is extracted with soybean leaf extract-containing soybean oil. The amount of soybean oil extract-containing soybean oil added is 0.02 to 2 weights per 1 weight of the fermented material. In this case, extraction by stirring is preferable, the stirring temperature is preferably 10 to 30 ° C., and the stirring time is preferably 0.5 to 3 hours.

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

After the isolated pinocembrin chalcone derivative is absorbed into the body, the excess amount is decomposed by esterase and further metabolized in the liver, so that it is highly safe and has few side effects.

Separating and purifying the target pinocembrin chalcone 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 a separation resin.

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 to separate and purify with a suitable separation solvent and remove the solvent to obtain the desired pinocembrin chalcone derivative.

The pinocembrin chalcone derivative thus obtained is obtained as a liquid or a powder. The obtained pinocembrin chalcone 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 above-mentioned food preparation is used for the purpose of anti-inflammation, rhinitis prevention, hay fever prevention, dermatitis prevention, muscle pain and muscle fatigue prevention, fatigue recovery, nutrition tonic, maintenance of liver function, and the like.

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 wt.-0.5 wt. Of astaxanthin and 0.01-0.5 wt. Of soybean leaf extract-containing soybean oil are contained in 1 wt. Of the pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production. The food formulation which consists of a composition is demonstrated.

The pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production referred to here may be any of a crude product, a mixture, a synthesized product, and a highly purified substance extracted and purified. Chalcone derivatives are pinocembrin chalcone, palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearin at the X position. Any one selected from acids is a covalently bonded derivative.

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

Furthermore, the pinocembrin chalcone derivative mentioned 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. A transcription factor is a derivative that suppresses gene level expression of inflammatory cytokines and suppresses production of inflammatory cytokines.

Astaxanthin is a kind of carotenoid pigment and is a red pigment produced by Haematococcus algae when exposed to sunlight. It is a natural substance contained in salmon and salmon roe, and its safety and strong antioxidant power have been verified.

Astaxanthin is obtained by supercritical extraction using carbon dioxide after culturing Haematococcus algae.

Astaxanthin manufactured by Takeda Paper Co., Ltd. and Fuji Chemical Co., Ltd. is preferable because of its high quality and low impurities.

Soybean oil containing persimmon leaf extract is pulverized with pulverizers from Japan, China, and Asia. Obtained by extraction.

Treated raw material of bamboo 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.

Astaxanthin is added in an amount of 0.01 to 0.5 wt. Per 1 wt. Of the pinocembrin chalcone derivative having an inhibitory effect on the production of inflammatory cytokines, and the bamboo leaf extract-containing soybean oil is 0.01 to 0.00 wt. 5 weight, which gives a composition.

When the weight of astaxanthin is less than 0.01 weight with respect to 1 weight of the pinocembrin chalcone derivative, the target composition may not be sufficiently obtained.

When the weight of astaxanthin exceeds 0.5 weight with respect to 1 weight of the pinocembrin chalcone derivative, the solubility of the pinocembrin chalcone derivative is lowered and may be precipitated.

When the weight of the soybean leaf extract-containing soybean oil is less than 0.01 weight per 1 weight of the pinocembrin chalcone derivative, the target composition may not be sufficiently obtained.

When the weight of the soybean leaf extract-containing soybean oil is more than 0.5 weight relative to 1 weight of the pinocembrin chalcone derivative, the solubility of the pinocembrin chalcone derivative is reduced and may be precipitated.

In order to obtain the said composition, it is preferable to heat after mixing. As heating conditions, the temperature is 30 to 45 ° C., and the heating time is 6 to 40 hours.

When the heating temperature is lower than 30 ° C, there is a possibility that sufficient reaction does not occur. When the heating temperature is higher than 45 ° C., the reaction product generated by oxidation may turn brown. When the heating time is less than 6 hours, a sufficient product may not be obtained. If the heating time exceeds 40 hours, the product produced by oxidation may turn brown.

This composition is preferable because the above-described pinocembrin chalcone derivative is continuously released little by little and becomes a continuous composition.

Moreover, by comprising in this way, a pinocembrin chalcone derivative is stably maintained by the antioxidant power of astaxanthin, 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 the purpose of anti-inflammation, prevention of rhinitis, hay fever, prevention of dermatitis, prevention of muscle pain and muscle fatigue, recovery from fatigue, nutrition and tonic, maintenance of liver function, and the like.

Next, 0.006 to 0.4 weight of astaxanthin and 0.05 to 0.8 weight of soybean leaf extract-containing soybean oil are contained in 1 weight of the pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production. The cosmetic comprising the composition will be described.

The pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production referred to here may be any of a crude product, a mixture, a synthesized product, and a highly purified substance extracted and purified. The chalcone derivative is palmitic acid, 14-methyl palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearic acid at the 8-position of pinocembrin chalcone Any one selected from the above is a covalently bonded derivative.

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

Furthermore, the pinocembrin chalcone derivative mentioned 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. A transcription factor is a derivative that suppresses gene level expression of inflammatory cytokines and suppresses production of inflammatory cytokines.

Astaxanthin is a kind of carotenoid pigment and is a red pigment produced by Haematococcus algae when exposed to sunlight. It is a natural substance contained in salmon and salmon roe, and its safety and strong antioxidant power have been verified.

Astaxanthin is obtained by supercritical extraction using carbon dioxide after culturing Haematococcus algae.

Astaxanthin manufactured by Takeda Paper Co., Ltd. and Fuji Chemical Co., Ltd. is preferable because of its high quality and low impurities.

Soybean oil containing persimmon leaf extract is pulverized with pulverizers from Japan, China, and Asia. Obtained by extraction.

Treated raw material of bamboo 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.

Astaxanthin to be added is 0.006 to 0.4 weight with respect to 1 weight of the pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production, and the bamboo leaf extract-containing soybean oil is 0.05 to 0.00 weight. 8 weight, which gives a composition.

When the weight of astaxanthin is less than 0.006 weight with respect to 1 weight of the pinocembrin chalcone derivative, the target composition may not be sufficiently obtained.

When the weight of astaxanthin exceeds 0.4 weight relative to 1 weight of the pinocembrin chalcone derivative, the solubility of the pinocembrin chalcone derivative is lowered and may be precipitated.

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

When the weight of the soybean leaf extract-containing soybean oil is more than 0.8 weight relative to 1 weight of the pinocembrin chalcone derivative, the solubility of the pinocembrin chalcone derivative may be reduced and may precipitate.

In order to obtain the said composition, it is preferable to heat after mixing. As heating conditions, the temperature is 30 to 45 ° C., and the heating time is 6 to 40 hours.

When the heating temperature is lower than 30 ° C, there is a possibility that sufficient reaction does not occur. When the heating temperature is higher than 45 ° C., the reaction product generated by oxidation may turn brown. When the heating time is less than 6 hours, a sufficient product may not be obtained.

If the heating time exceeds 40 hours, the product produced by oxidation may turn brown.

This composition is preferable because the above-described pinocembrin chalcone derivative is continuously released little by little and becomes a continuous composition.

Moreover, by comprising in this way, a pinocembrin chalcone derivative is stably maintained by the antioxidant power of astaxanthin, 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, an anti-inflammatory agent composed of the pinocembrin chalcone derivative having the above-mentioned inhibitory action on inflammatory cytokine production will be described.

The pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production referred to here may be any of a crude product, a mixture, a synthesized product, and a highly purified substance extracted and purified. The chalcone derivative is palmitic acid, 14-methyl palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, methyl stearic acid at the 8-position of pinocembrin chalcone Any one selected from the above is a covalently bonded derivative.

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

Furthermore, the pinocembrin chalcone derivative mentioned 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. A transcription factor is a derivative that suppresses gene level expression of inflammatory cytokines and suppresses production of inflammatory cytokines.

When used as a pharmaceutical, since it is necessary to remove the influence of impurities, it is preferable to use a pinocembrin chalcone 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.

It exerts an effect 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 obese 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 pinocembrin chalcone derivative obtained by fermentation will be described.

100 eels (scientific name: Angulara japonica) 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 1.8 kg were cut with a knife and pulverized with DM-6 manufactured by Nakayama Institute of Technology.

This was put into a clean culture tank, and 3.5 L of tap water was added. To this, red pine leaves collected in Shizuoka Prefecture cultivated without pesticides, that is, 1.8 kg of pine, were washed with tap water, dried with a dryer (type Nishimura Kikai, GZQ3 type), and cut with scissors. Then, it was pulverized with DM-6 manufactured by Nakayama Technical Research Institute. 180 g of this pulverized product was added to the above cylinder. To this, Chinese soybean was washed with water, heated to 36 ° C. for 36 minutes, and 1.8 kg of soybean pulverized product was further added.

To this, 18 g of natto bacteria manufactured by Natto Motopo was added. Fermentation was carried out at a temperature of 36 ° C. with stirring for 47 hours.

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

On the other hand, 2.1 kg of the young leaves of Gifu prefecture grown in pesticide-free cultivation was dried for 11 hours with a dryer (Nishimura Kikai, GZQ3 type), and a pulverizer (Sanchi Seisakusho, Sanriki Universal Crusher) Machine) to a particle size of about 0.7 μm.

19 g of cellulase (Y-NC) manufactured by Yakult Pharmaceutical Co., Ltd. was added to 1.9 kg of the pulverized product, and the mixture was stirred at 27 ° C. for 11 hours. Soybean oil was added to the resulting pulverized product and stirred to prepare a soybean leaf extract-containing soybean oil.

To the fermented product, 1 kg of the soybean leaf extract-containing soybean oil was added and stirred for 1 hour and mixed.

The oil-soluble portion separated by the soybean leaf extract-containing soybean oil that was allowed to stand and 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 pinocembrin chalcone derivative was obtained as an oily substance. This was used as the sample of Example 1.

The following describes the preparation of pinocembrin chalcone derivatives covalently bound to valmitic acid.

9 kg of green tea from Shizuoka cultivated without agricultural chemicals, scientific name Camellia sinensis, was thoroughly washed with tap water and dried with a dryer.

3 kg of this green tea was subjected to a pulverizer (manufactured by Sanriki Seisakusho, Sanroku Universal Crusher) and pulverized to obtain a green tea pulverized product.

1 kg of crushed green tea was put into a clean cylinder and 10 L of tap water was added. To this, 300 g of valmitic acid purchased from Ryoshoku was added and stirred.

To this was added 11 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 26 ° C. and stirred at a rate of 67 times / minute for 11 hours to obtain a heated solution.

On the other hand, 1.8 kg of the young leaves of Tominyu from Japan are dried for 12 hours with a dryer (manufactured by Nishimura Kikai, GZQ3 type), and the particle size is 0.7 with a grinder (manufactured by Sanriki Seisakusho, a three-powered universal grinder). Milled to micro m.

17 g of cellulase (Y-NC) manufactured by Yakult Pharmaceutical Co., Ltd. was added to 1.7 kg of the pulverized product, and the mixture was stirred at 26 ° C. for 12 hours. The obtained pulverized product was extracted with soybean oil to prepare soybean oil extract-containing soybean oil.

After cooling the cylinder containing the warming solution with tap water, 1 kg of the soybean leaf extract-containing soybean oil was added, and the oil portion was collected.

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

Hereinafter, preparation of pinocembrin chalcone derivative to which 14-methylpalmitic acid is bound will be described.

10 kg of red pine pine grown in Shizuoka, which was cultivated without pesticides, was thoroughly washed with tap water and dried with a dryer (GZQ3 type, manufactured by Nishimura Kikai Co., Ltd.). This was used as a raw material, Matsuba.

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

1 kg of pulverized matsuba was put in a clean cylinder and 10 L of tap water was added. To this, 300 g of 14-methyl 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 25 ° C. and stirred at a rate of 58 times / minute for 10 hours to obtain a heated solution.

On the other hand, 2 kg of the young leaves of Tominyu from Japan are dried for 12 hours using a dryer (Nishimura Kikai, GZQ3 type), and the particle size is 0.7 μm using a pulverizer (Sanroku Seisakusho, Sanroku Universal Crusher). To grind.

18 g of cellulase (Y-NC) manufactured by Yakult Pharmaceutical Co., Ltd. was added to 1.8 kg of the pulverized product, and the mixture was stirred at 25 ° C. for 14 hours. The obtained pulverized product was extracted with soybean oil to prepare soybean oil extract-containing soybean oil.

After cooling the cylinder containing the warming solution with tap water, 1 kg of the soybean leaf extract-containing soybean 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 pinocembrin chalcone derivative bound with 14-methylpalmitic acid as an oily liquid. This was also used as the sample of Example 3.

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

12 kg of red pine pine grown in Shizuoka grown without chemicals was collected, washed thoroughly with tap water, and dried with a dryer. This was used as a raw material, Matsuba. 2.4 kg of this matsuba was subjected to a pulverizer (manufactured by Sanriki Seisakusho Co., Ltd., a three-purpose universal pulverizer) and pulverized to obtain a pulverized product of matsuba.

1.1 kg of tap water was added to 1.1 kg of pulverized material of Matsuba in a clean cylinder. To this, 290 g of Eicosapentaenoic acid manufactured by Nippon Suisan was added and stirred.

To this was added 11 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 25 ° C. and stirred at a rate of 61 times / minute for 11 hours to obtain a heated solution.

On the other hand, 2 kg of young leaves of Tominyu from Japan were dried with a dryer for 12 hours, and pulverized to a particle size of 0.7 μm by a pulverizer (manufactured by Sanriki Seisakusho, Sanroku Universal Crusher).

18 g of cellulase (Y-NC) manufactured by Yakult Pharmaceutical Co., Ltd. was added to 1.8 kg of the pulverized product and stirred at 25 ° C. for 12 hours. The obtained pulverized product was extracted with soybean oil to prepare soybean oil extract-containing soybean oil.

After cooling the cylinder containing the warming solution with tap water, 1 kg of the soybean leaf extract-containing soybean oil 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 pinocembrin chalcone derivative to which eicosapentaenoic acid was bound as an oily liquid. This was also used as the sample of Example 4.

The preparation of pinocembrin chalcone derivative bound with docosahexaenoic acid is described below.

13 kg of Shizuoka pine pine grown in pesticide-free was collected, washed thoroughly with tap water, and dried with a drier (GZQ3 type, manufactured by Nishimura Kikai). This was used as a raw material, Matsuba.

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

1.1 kg of pulverized matsuba was put in a clean cylinder and 10 L of tap water was added. To this, 330 g of docosahexaenoic acid manufactured by Nissui Pharmaceutical was added and stirred.

To this was added 11 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 25 ° C. and stirred at a rate of 55 times / minute for 10 hours to obtain a heated solution.

On the other hand, 2 kg of the young leaves of Tominyu from Japan are dried for 12 hours with a dryer (manufactured by Nishimura Kikai Co., Ltd., model GZQ3), and the particle size is 0.7 micron with a pulverizer (manufactured by Sanriki Seisakusho Co., Ltd.) c. 18 g of cellulase (Y-NC) manufactured by Yakult Pharmaceutical Co., Ltd. was added to 1.8 kg of the pulverized product and stirred at 25 ° C. for 12 hours. The obtained pulverized product was extracted with soybean oil to prepare soybean oil extract-containing soybean oil.

After cooling the cylinder containing the warming solution with tap water, 1 kg of the soybean leaf extract-containing soybean oil 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 pinocembrin chalcone 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 pinocembrin chalcone derivative will be described.

30 g of the pinocembrin chalcone derivative obtained in Example 4 was suspended in 1.2 L of ethanol and applied to a column packed with 480 g of Diaion manufactured by Mitsubishi Chemical. This was washed with 850 mL of 10% ethanol-containing water. Further, after washing with 500 mL of 35% ethanol-containing water, elution was performed with 500 mL of 80% ethanol-containing water, and a fraction of 80% 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 pinocembrin chalcone derivative was obtained by a freeze dryer manufactured by Nippon FD. This was used as the sample of Example 6.

Hereinafter, an identification test of the pinocembrin chalcone derivative will be described.
(Test Example 1)

Each of the pinocembrin chalcone derivatives obtained in Example 1, Example 2, Example 3, Example 4, Example 5, Example 5 and Example 6 obtained as described above was dissolved in purified ethanol, and mass spectrometry was performed. The analysis was performed with a high performance liquid chromatography equipped with an instrument (HPLC, Shimadzu Corporation), and further analyzed with a nuclear magnetic resonance apparatus (NMR, Bruker, AC-250).

As a result, from the sample of Example 1, as the pinocembrin chalcone derivative, at the 8-position of pinocembrin chalcone, palmitic acid, 14-methyl palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipolipin Pinocembrin chalcone derivatives to which acid, gamma-linolenic acid, stearic acid, and methyl stearic acid were bound were identified.

Further, from the sample of Example 2, a pinocembrin chalcone derivative in which palmitic acid was bonded to the 8-position of pinocembrin chalcone was identified. The carbon farthest from the carboxylic acid of palmitic acid was covalently bonded.

Further, from the sample of Example 3, a pinocembrin chalcone derivative in which 14-methylpalmitic acid was bonded to the 8-position of pinocembrin chalcone was identified. The carbon farthest from the carboxylic acid of 14-methylpalmitic acid was covalently bonded.

Further, from the samples of Example 4 and Example 6, a pinocembrin chalcone derivative in which eicosapentaenoic acid was bonded to the 8-position of pinocembrin chalcone was identified. The carbon farthest from the carboxylic acid of eicosapentaenoic acid was covalently bonded.

Further, from the sample of Example 5, a pinocembrin chalcone derivative in which docosahexaenoic acid was bonded to the 8-position of pinocembrin chalcone was identified. The carbon farthest from the carboxylic acid of docosahexaenoic acid was covalently bonded.

Below, the suppression test of the inflammatory cytokine production of a pinocembrin chalcone derivative is demonstrated.
(Test Example 2)
In the test, heparinized blood was collected from 4 males aged 21 to 77 years old and 4 females aged 29 to 65 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%, the addition amount of 1 ng is 60% in Example 1, 57% in Example 2, 50% in Example 3, It was 42% in Example 4, 44% in Example 5, and 36% in Example 6. In addition, clobetasol propionate was 61%.

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 interleukin-6, when the amount of the solvent control is 100%, the added amount of 1 ng is 76% in Example 1, 79% in Example 2, 71% in Example 3, and Example. It was 70% in Example 4, 79% in Example 5, and 67% in Example 6. In addition, clobetasol propionate was 79%.

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 is 59% in Example 1, 65% in Example 2, 59% in Example 3, and in Example 4. It was 49%, 55% in Example 5, and 33% in Example 6. In addition, clobetasol propionate was 72%.

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 as clobetasol propionate.

Hereinafter, the production of a food preparation containing a pinocembrin chalcone derivative will be described.

100 g of the pinocembrin chalcone derivative obtained in Example 1 was placed in a food processing mixer (Tsukasa, Pau mixer, single type), and 25 g of Astaxanthin made by Takeda Kaiki was added. To this was added 11 g of soybean leaf extract-containing soybean oil, and this was heated at 37 ° C. for 24 hours with stirring, and then cooled to obtain about 120 g of a composition.

To 100 g of this composition, 300 g of edible cellulose, 1 g of ascorbic acid and 9 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.

The anti-inflammatory action using food preparations will be described below.
(Test Example 3)

In 6 males presenting scabs and honey with 35-69 year old cedar pollen, 10 capsules of the food preparation obtained in Example 7 once a day, ie 2.5 g per day, 14 Feeded daily for days. The reactivity with cedar pollen was observed before feeding and on the 14th day of feeding. Furthermore, blood was collected before feeding and on the 14th day of feeding, and the IgE amount was measured by an immunoantibody method.

As a result, after feeding, the number of scabs and honeyworms caused by cedar pollen was 34% on average compared to before feeding, and a clear decrease in reactivity was observed.

Furthermore, the blood IgE amount was 42% 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.

110 g of the pinocembrin chalcone derivative obtained in Example 2 was placed in a cosmetic processing mixer (Pure Container Mixer, manufactured by Kotobuki Industries), and 11 g of Astaxanthin manufactured by Takeda Paper Instruments was added.

To this was added 50 g of soybean oil extract-containing soybean oil, and this was heated at 37 ° C. for 30 hours with stirring and cooled to obtain about 160 g of a composition.

This composition was put in the mixer, and 1 kg of beeswax (manufactured by API) and 1 g of squalane (manufactured by Nihon Suisan) 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 pinocembrin chalcone derivative obtained in Example 2 was prepared.
(Test Example 4)

Using the cream obtained in Example 8, a wrinkle improvement test against ultraviolet rays was conducted on 10 women aged 23 to 78 years. That is, 10 cases were divided into 2 groups, and 1 g of cream containing the pinocembrin chalcone derivative of Example 8 was applied to the face part for 7 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 7 days of use, skin skin temperature and skin area per unit area using skin elasticity, skin surface horny layer moisture content measuring device (IBS, SKICON200) using keratin moisture content, elasticity meter (ctometer) 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 use example of the cream containing the pinocembrin chalcone derivative as compared with the cream using only the base material, an average skin temperature decrease of 0.41 ° C. was observed. In addition, the skin surface horn layer moisture content increased to 179% in the use example of the cream containing the pinocembrin chalcone derivative as compared with the use of the cream of the base material alone. Further, the elasticity of the elasticity meter was increased to 199% in the usage example of the cream containing the pinocembrin chalcone derivative as compared to the cream using the base material alone.

The wrinkle length was 55% in the use example of the cream containing the pinocembrin chalcone derivative as compared with the use of the cream containing only the base material, and a wrinkle reduction was clearly observed.

In addition, the amount of TNF alpha in sweat and sebum was reduced to 63% on average in the use case of the cream containing the pinocembrin chalcone derivative, compared to the use of the base-only cream.

In addition, the cream containing the pinocembrin chalcone derivative had 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.

Hereinafter, an anti-inflammatory agent comprising a pinocembrin chalcone derivative will be described.

40 g of pinocembrin chalcone derivative obtained in Example 2 above, 110 g of lanolin, 130 g of macro gold, 10 g of beeswax, and 20 g of ozokerite were added to a clean stainless steel dissolution tank and dissolved at 30 ° 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 pinocembrin chalcone derivative obtained in Example 2 was prepared, and used as a control sample in the test.
(Test Example 5)

Four men and three women presenting scabs and honeyworms with 30-59 year old cedar pollen were treated with 1 g of the anti-inflammatory agent obtained in Example 9 once a day for 14 days. And applied to the perioral area.

The reactivity with cedar pollen was observed before application and 14 days after 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 expression of scabs and honeyworms by cedar pollen was 31% on average compared to before application, and a decrease in reactivity to pollen was observed in all cases. The average amount of TNF alpha in the blood was 30% compared to that before application, and a decrease in the amount of TNF alpha, which is an inflammatory cytokine, was observed.

The blood IgE amount was 44% of the value before application, and a decrease in the IgE amount was observed. In addition, after application, no abnormality was observed in physical condition, health condition, or other clinical laboratory values.

Therefore, an anti-inflammatory agent comprising a pinocembrin chalcone derivative has reduced inflammatory cytokine and IgE levels against hay fever, exhibits an excellent anti-inflammatory effect, and is also confirmed to be safe.

On the other hand, when a control sample using lanolin was used in place of the pinocembrin chalcone derivative, the number of scabs and honeyworms produced by cedar pollen was 102% on average compared to before application, and the reaction to pollen There was no change in sex.

Further, the amount of TNF alpha in the blood was 101% on average as compared with that before application, and the amount of TNF alpha, which is an inflammatory cytokine, did not change.

The blood IgE level was 104% on average, and no change was observed.

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

In addition, the food preparation comprising the pinocembrin chalcone derivative having an inhibitory action on the production of inflammatory cytokine according to the present invention improves or prevents the onset of inflammation such as hay fever, sick house syndrome, cold, allergy, dermatitis, etc. It contributes to improving the quality of life.

Furthermore, cosmetics comprising a pinocembrin chalcone derivative having an inhibitory action on the production of inflammatory cytokines show an improvement or prevention effect against wrinkles and dullness due to sunburn, inflammation such as skin inflammation and atopy, and improve public QOL. Is.

In addition, an anti-inflammatory agent comprising a pinocembrin chalcone derivative having an inhibitory action on the production of inflammatory cytokines can be used to improve or prevent inflammation such as dermatitis, hepatitis, encephalitis, pneumonia, cold, pancreatitis, hay fever and allergies. Contribute and improve people's lives. 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 heads and internal organs of pine 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 pinocembrin chalcone derivative represented by the following formula (1) having an inhibitory action on inflammatory cytokine production.

X is any one selected from palmitic acid, 14-methylpalmitic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, alpha-lipoic acid, gamma-linolenic acid, stearic acid, and methyl stearic acid. The pinocembrin chalcone derivative according to claim 1, which is obtained by adding palmitic acid and lipase for transesterification to a pulverized product of Matsuba or green tea, heating and extracting with soybean oil containing persimmon leaf extract. A pinocembrin chalcone derivative represented by the following formula (2) having a suppressive action on inflammatory cytokine production, wherein is palmitic acid.

The pinocembrin chalcone derivative according to claim 1, which is obtained by adding 14-methylpalmitic acid and lipase for transesterification to a pulverized product of Matsuba or green tea, heating and extracting with soybean oil containing persimmon leaf extract. Among them, a pinocembrin chalcone derivative represented by the following formula (3) having an inhibitory action on inflammatory cytokine production, wherein X is 14-methylpalmitic acid.

The pinocembrin chalcone derivative according to claim 1, which is obtained by adding eicosapentaenoic acid and lipase for transesterification to a pulverized product of Matsuba or green tea, heating and extracting with soybean leaf extract-containing soybean oil. A pinocembrin chalcone derivative represented by the following formula (4) having an inhibitory action on inflammatory cytokine production, wherein X is eicosapentaenoic acid.

The pinocembrin chalcone derivative according to claim 1, which is obtained by adding docosahexaenoic acid and lipase for transesterification to a pulverized product of Matsuba or green tea, heating and extracting with soybean oil containing persimmon leaf extract. A pinocembrin chalcone derivative represented by the following formula (5) having a suppressive action on inflammatory cytokine production, wherein is docosahexaenoic acid.

The pino assembly which has an inflammatory cytokine production inhibitory effect of Claim 1 obtained by extracting the fermented material which added fermented natto to fermented fish, a pine or green tea, and soybean with the soybean leaf extract containing soybean oil. N chalcone derivative. Claims 1 or 2 or Claim 3 or Claim 4 or Claim 5 or Claim 6 of the pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production in an amount of 0.01 to 0. A food preparation comprising a composition containing 5 wt. Claims 1 or 2 or Claim 3 or Claim 4 or Claim 5 or Claim 6 of the pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production of 1 weight of astaxanthin 0.006 to 0.00. A cosmetic product comprising a composition containing 4 wt.%, Bamboo leaf extract-containing soybean oil 0.05-0.8 wt. An anti-inflammatory agent comprising the pinocembrin chalcone derivative having an inhibitory action on inflammatory cytokine production according to claim 1, claim 2, claim 3, claim 4, claim 5, or claim 6.