JP2009001515A - Isoflavone derivative having estrogen-adjusting action, food preparation, cosmetic, and endometriosis remedy each comprising the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an isoflavone derivative having weak side effects and an excellent estrogen-adjusting action, and to provide a food preparation, a cosmetic, and an endometriosis remedy each comprising the same. <P>SOLUTION: This isoflavone derivative having the excellent estrogen-adjusting action is a derivative prepared by ester-bonding isoflavone to a fatty acid, and is obtained by mixing a crushed product of black Ficus carica fruits or Trifolium pratense flowers, foliages or seeds with a lipase for transesterificatoin and then heating the mixture, or by fermenting fishes and soybeans with Bacillus natto and then extracting the fermentation product with a vegetable oil. The food preparation or cosmetic comprises the isoflavone derivative, a chrysanthemum flower extract-containing vegetable oil and a pine needle extract-containing vegetable oil. The endometriosis remedy comprises the isoflavone derivative having an estrogen-adjusting action. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

The present invention relates to an isoflavone derivative having an estrogen regulating action. The present invention also relates to a food preparation, a cosmetic and a treatment for endometriosis comprising a composition containing the aforementioned isoflavone derivative, chrysanthemum flower extract-containing vegetable oil, and pine needle extract-containing vegetable oil.

A compound exhibiting an estrogen-like action is present in daily life and has been identified as an endocrine disrupting substance. The adverse effects of endocrine disrupting substances on reproductive function and the uterus are scientifically discussed (for example, Non-Patent Document 1). reference.).

There are many women who suffer from endometriosis. In Japan alone, hundreds of thousands of women have been reported, and research on therapeutic agents and improvement methods for endometriosis is also underway (see, for example, Non-Patent Document 2). .

The causal relationship between endometriosis and endocrine disrupting substances lurking in daily life and lifestyle habits has also attracted attention, and attention has also been paid to the review of daily eating habits (see Non-Patent Document 3, for example).

Among plants, it has been studied that isoflavones exhibit a female estrogenic effect on soybeans belonging to legumes, and daily intake of soy milk and processed soybean foods is being promoted.

On the other hand, the intake and safety of isoflavones have also been studied, but no conclusion has been reached, and the guidelines of the Ministry of Health, Labor and Welfare have called attention to excessive intake of pure isoflavones (for example, non-patents). Reference 4).

Although prodestrone derivative danazol and gonadal stimulating estrogen modulators buserelin and goserelin are used as treatments for endometriosis, side effects such as masculinization, thrombosis, liver damage, estrogen abnormalities, and osteoporosis have been reported. (For example, refer nonpatent literature 5.) The chemical | medical agent with higher safety | security is calculated | required.

Isoflavone obtained from soybean is known as a naturally occurring substance with estrogen-regulating action, and it is also used in food for specified health use, but its estrogen-regulating action is mild, so it is used in large quantities. is required. However, a large amount of ingestion is a concern due to side effects on the genitals.

Regarding the invention related to the treatment of endometriosis with clover-derived isoflavones, in "Methods for treating estrogen-related diseases", the treatment, prevention, improvement or prevention of diseases associated with abnormally highly active steroidal estrogens An extract comprising clover or chickpea isoflavones, or about 2: 1 to about 5: 1 of one or more isoflavones from the group of biocanin, or biocanin and formononetin, daidzein, and genistein. A method comprising administering to a human patient a composition comprising a clover or chickpea extract comprising a ratio, optionally with one or more pharmaceutically acceptable carriers, excipients, adjuvants and / or diluents , And a composition containing the isoflavone-containing extract and method of use thereof ” However, identification of a new substance that exhibits an action has not been achieved, and it is limited to existing substances (for example, see Patent Document 1).

As for the treatment of endometriosis with isoflavone, there is an invention of “treatment of non-malignant disease or disease using anti-ErbB2 antibody”, but the substance has not yet been identified. (For example, see Patent Document 2.)

Red clover is also referred to as red clover, and as an invention relating to the estrogen regulating action by red clover, “female hormone production promoter and skin external preparation containing the same” is seen, but it is an invention of existing isoflavones and is a novel substance It has not reached. (For example, refer to Patent Document 3.)

In addition, there is no invention relating to estrogen action relating to black figs.

The invention relating to cosmetics utilizing the estrogenic action of isoflavones includes “a cosmetic and / or dermatological and / or pharmaceutical composition for topical application comprising at least one inhibitor of 3-beta-HSD enzyme” (for example, , And Patent Document 4) and "Methods for Enhancing the Potency of Locally Active Ingredients with Monoacyl- (lyso) -glycerophospholipids and Their Uses" (for example, see Patent Document 5), It is not an action.

In any of the above inventions, components and derivatives identified as useful novel substances have not been identified, and their functions have not been confirmed.

Because of these current conditions, pharmaceuticals, cosmetics, foods, and other industries have natural side effects that have fewer side effects and can be used for a long period of time, against endometriosis-related diseases that are increasing. Plant-derived ingredients and pharmaceuticals, cosmetics, and foods using the same are highly desired.
Special Table 2002-507568 Special table 2006-516117 gazette JP 2004-0675590 A JP 2003-081875 A JP 2002-128702 A Health Sanitation Safety Standards Household Goods Regulation Law-related practical manual, Tsurubo Kenshiro: Life Hygiene, Vol. 43, No. 5, 1999. Actual data on endometriosis, Japan Endometriosis Association, 2001. Tsuchiya, M et al., Fertil. Steril, Vol 84, 454-458, 2005. Ministry of Health, Labor and Welfare, Food Evaluation for Specific Health, Soy Isoflavone 40, 2005. Szeplaki, G, et al., The Journal of allergy and Clinical immunology, Vol 115, 864-869, 2005.

Although isoflavones have been used as conventional natural estrogen-regulating substances, their functions are mild and have not led to sufficient estrogen-regulating actions and improvement of endometriosis. There is also a limit on the amount of use.

In addition, side effects such as masculinization, thrombosis, liver dysfunction, acne, and genital bleeding have been observed in chemically synthesized compounds that exhibit estrogen-regulating action, such as danazol.

Furthermore, although buserelin acetate is a preparation exhibiting a gonad-stimulating estrogen regulating action, side effects such as osteoporosis and the appearance of menopause-like symptoms are observed.

Since these synthetic drugs have side effects, there are limitations on the period of use and the amount of use.

The present invention has been made paying attention to the problems existing in the prior art as described above. The object is to provide an isoflavone derivative having weak side effects and having an excellent estrogen regulating action.

In addition, black fig fruits or red clover flowers or leaf stems or seeds are pulverized with palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, alpha-lipo An object of the present invention is to provide an isoflavone derivative having an excellent estrogen-regulating action, with less side effects obtained by adding an acid, heating and extraction with a vegetable oil.

Isoflavones that have excellent estrogen-regulating effects, with weak side effects obtained by extraction with edible fish, black fig fruit or red clover flowers or leaf stems or seeds and fermented fermented soybeans with fermented natto It is to provide a derivative.

Furthermore, the side effect which consists of a composition containing 0.01 to 0.5 weight of chrysanthemum flower extract containing vegetable oil and 0.01 to 0.5 weight of pine leaf extract containing vegetable oil in 1 weight of isoflavone derivative having an estrogen regulating action Is to provide an excellent food preparation.

In addition, it comprises a composition containing 0.05 to 0.8 weight of chrysanthemum flower extract-containing vegetable oil and 0.05 to 0.8 weight of pine leaf extract-containing vegetable oil in 1 weight of isoflavone derivative having an estrogen regulating action. It is to provide excellent cosmetics with weak side effects.

Another object of the present invention is to provide a therapeutic agent for endometriosis which has an excellent estrogen-regulating action and has low side effects consisting of an isoflavone derivative.

In order to achieve the above object, the invention according to claim 1 relates to an isoflavone derivative represented by the following formula (1) having an estrogen regulating action.

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

The invention of claim 2 is obtained by adding palmitic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating and extracting with vegetable oil, Among the isoflavone derivatives according to Item 1, the present invention relates to an isoflavone derivative represented by the following formula (2) having an estrogen regulating action in which X and Y are hydrogen and Z is palmitic acid.

The invention according to claim 3 is obtained by adding eicosapentaenoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating, extracting with vegetable oil, Among the isoflavone derivatives according to claim 1, the present invention relates to an isoflavone derivative represented by the following formula (3) having an estrogen regulating action in which X and Y are hydrogen and Z is eicosapentaenoic acid.

The invention according to claim 4 is obtained by adding docosahexaenoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating and extracting with vegetable oil, Among the isoflavone derivatives according to Item 1, the present invention relates to an isoflavone derivative represented by the following formula (4) having an estrogen regulating action in which X and Y are hydrogen and Z is docosahexaenoic acid.

The invention according to claim 5 is obtained by adding benzoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating, extracting with vegetable oil, Among the isoflavone derivatives according to Item 1, the present invention relates to an isoflavone derivative represented by the following formula (5) having an estrogen regulating action in which X and Y are hydrogen and Z is benzoic acid.

The invention according to claim 6 is obtained by extracting a fermented product obtained by adding fermented natto to fermented fish, black fig fruit or red clover flower or leaf stem or seed and soybean and fermenting with vegetable oil. And an isoflavone derivative having an estrogen-modulating action described in 1. above.

The invention according to claim 7 is a chrysanthemum flower extract added to 1 weight of the isoflavone derivative having an estrogen regulating action according to claim 1, claim 2, claim 3, claim 4, claim 5, or claim 6. The present invention relates to a food preparation comprising a composition containing 0.01 to 0.5 weight of vegetable oil and 0.01 to 0.5 weight of pine leaf extract-containing vegetable oil.

The invention according to claim 8 is a chrysanthemum flower extract added to 1 weight of the isoflavone derivative having an estrogen regulating action according to claim 1, claim 2, claim 3, claim 4, claim 5, or claim 6. The present invention relates to a cosmetic comprising a composition containing 0.05 to 0.8 weight of vegetable oil and 0.05 to 0.8 weight of pine leaf extract-containing vegetable oil.

The invention according to claim 9 is a therapeutic agent for endometriosis comprising the isoflavone derivative having an estrogen-regulating action according to claim 1 or claim 2 or claim 3 or claim 4 or claim 5 or claim 6. It is about.

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

According to the isoflavone derivative of claim 1, side effects are weak and an excellent estrogen regulating action is exhibited.

According to the isoflavone derivative obtained by adding caprylic acid and lipase for transesterification to a ground product of black fig fruit or red clover flower or leaf stem or seed according to claim 2, heating and extracting with vegetable oil Side effects are weak, and an excellent estrogen regulating effect is exhibited.

According to the isoflavone derivative obtained by adding palmitic acid and lipase for transesterification to a ground product of black fig fruit or red clover flower or leaf stem or seed according to claim 3, heating and extracting with vegetable oil Side effects are weak, and an excellent estrogen regulating effect is exhibited.

According to an isoflavone derivative obtained by adding eicosapentaenoic acid and lipase for transesterification to a ground product of black fig fruit or red clover flower or leaf stem or seed according to claim 4, heating and extracting with vegetable oil Therefore, side effects are weak and an excellent estrogen regulating action is exhibited.

According to the isoflavone derivative obtained by adding docosahexaenoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed according to claim 5, heating and extracting with vegetable oil Side effects are weak, and an excellent estrogen regulating effect is exhibited.

According to the edible fish according to claim 6, black fig fruit or red clover flower or leaf stem or seed and soybean fermented fermented product obtained by adding natto to fermented with vegetable oil, Side effects are weak, and an excellent estrogen regulating effect is exhibited.

A food preparation comprising a composition containing 0.01 to 0.5 weight of chrysanthemum flower extract-containing vegetable oil and 0.01 to 0.5 weight of pine leaf extract-containing vegetable oil in 1 weight of the isoflavone derivative according to claim 7. According to the method, side effects are weak and an excellent estrogen regulating action is exhibited.

A cosmetic comprising a composition containing 1 to 1 weight of the isoflavone derivative according to claim 8 and 0.05 to 0.8 weight of chrysanthemum flower extract-containing vegetable oil and 0.05 to 0.8 weight of vegetable oil containing pine needle extract. According to this, side effects are weak and an excellent estrogen regulating action is exhibited.

According to the endometriosis drug comprising the isoflavone derivative according to claim 9, the side effect is weak and an excellent estrogen regulating action is exhibited.

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

First, an isoflavone derivative represented by the following formula (1) having an estrogen regulating action will be described.

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

In the first place, isoflavones are polyphenols biosynthesized by plants and microorganisms.

The isoflavone derivative as used herein has an isoflavone skeleton having palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, as represented by the formula (1). It is a derivative to which any one selected from alpha-lipoic acid is bound.

The isoflavone derivative is a substance of any one of palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid on the isoflavone molecule of the mother nucleus. Carboxylic acid groups are ester-bonded.

Although the above isoflavones are widely distributed in black fig fruits or red clover flowers or leaf stems or seeds, stems, leaves and roots, there is a disadvantage that the structure of isoflavones is unstable, and the above isoflavone derivatives are structural It is preferable because it is stable and has an excellent estrogen regulating action.

The above isoflavone derivatives are soluble in fat by binding any one of palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid. As a result, the structure of the isoflavone derivative is stabilized, and the estrogen regulating action is superior to that of isoflavone alone.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as a nuclear estrogen receptor of a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain and bleeding.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, estrogen is deficient in a state where estrogen is depleted or decreased, for example, in the case of menopause or irregular physiology. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue.

Moreover, since it is a structure with high fat solubility, there exists an advantage that it is easy to penetrate | invade inside a structure | tissue and an amount exhibits an estrogen control action at least. In addition, since it is decomposed by locally existing esterase to become isoflavone and fatty acid, the action is not sustained and safety is high.

Estrogen also has an important role in the brain. That is, protection of nerve cells. Since estrogen exhibits a brain-protecting effect, dementia is likely to occur in women who have entered menopause.

Since the isoflavone derivative has high fat solubility, it easily passes through the blood-brain barrier and works to protect brain neurons. However, since excessive amounts are degraded by esterases in the brain, side effects due to excessive intake are mild.

The isoflavone derivative is any one selected from palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid, which have high fat-soluble characteristics. Because one is bound, it is easier to penetrate the cell membrane of the small intestine and skin than is isoflavone, and is easily absorbed by the body.

When the isoflavone derivative is ingested and absorbed excessively, the excess amount is decomposed by the esterase in the blood, and each isoflavone and each palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearin Although it is decomposed into any of acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid, since the safety of each substance has been confirmed, the above isoflavone derivatives are also highly safe.

Among the above isoflavone derivatives, when X is hydrogen and Y is hydrogen, the target isoflavone derivative is a formononetin derivative because the isoflavone serving as the skeleton is formononetin.

Of the above isoflavone derivatives, when X is hydrogen and Y is a hydroxyl group, the skeleton isoflavone is biocanin A, so the target derivative is biocanin A derivative.

Among the above isoflavone derivatives, when X is a hydroxyl group and Y is hydrogen, the skeleton isoflavone is 2'-hydroxyformononetin, so the target derivative is a 2'-hydroxyformononetin derivative. is there.

Among the above isoflavone derivatives, when X is a hydroxyl group and Y is a hydroxyl group, the skeleton isoflavone is 2′-hydroxybiocanin A, so the target derivative is a 2′-hydroxybiocanin A derivative. is there.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is palmitic acid, saturated fatty acid residues of palmitic acid easily penetrate into the cell membrane and are absorbed into the cell, enhancing the estrogen regulating action. Is preferable.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is eicosapentaenoic acid, the unsaturated fatty acid residue of eicosapentaenoic acid exhibits a suppressive action on the production of inflammatory cytokines and inflammatory prostaglandins. From the above, it is preferable because the estrogen regulating action is stably exhibited while suppressing the inflammatory action. In particular, it is more preferable because it suppresses the expression of interleukin 6 that is highly painful and induces osteoporosis.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is docosahexaenoic acid, the unsaturated fatty acid residue of docosahexaenoic acid exhibits inflammatory prostaglandin production inhibitory action, thus suppressing the inflammatory action. However, it is preferable because it exerts an estrogen regulating action.

Among the above isoflavone derivatives, when X and Y are hydrogen or hydroxyl group and Z is benzoic acid, the residue of benzoic acid exhibits antibacterial action, so that estrogen regulation is achieved while suppressing bacterial infection at the inflammatory site It is preferable because of its action.

Among the above-mentioned isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is capric acid, the fatty acid residue of capric acid penetrates the cell membrane and is easily absorbed into the cell, thereby enhancing the estrogen regulating action. This is preferable.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is stearic acid, the saturated fatty acid residue of stearic acid easily penetrates into the cell membrane and is absorbed into the cell, enhancing the estrogen regulating action. Is preferable.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is gamma-linolenic acid, unsaturated saturated fatty acid residues of gamma-linolenic acid penetrate into the cell membrane and are easily absorbed into the cell, This is preferable because the estrogen regulating action is enhanced.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is docosapentaenoic acid, the unsaturated fatty acid residue of docosapentaenoic acid exhibits an inflammatory prostaglandin production inhibitory action, This is preferable because the estrogen regulating action is stably exhibited while suppressing the inflammatory action.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is alpha-lipoic acid, the fatty acid residue of alpha-lipoic acid exhibits an antioxidant action, thereby suppressing the oxidation of inflamed tissues. The estrogen regulating action is preferable since it is stably exhibited.

In addition, it is easy to obtain and economical to process isoflavone derivatives from black fig fruits or red clover flowers or leaf stems or seeds, pulverize them, extract them with organic solvents or vegetable oils, and purify them. ,preferable.

Here, as the organic solvent used for extraction, methanol, ethanol, chloroform, hexane, ethyl acetate, benzene, ether or the like is used, and among them, ethanol for food processing or ethanol containing water is preferable because of its high use range.

In addition, it is more preferable to use an organic solvent containing a pine leaf extract, a kokushi extract, a green tea extract, a chrysanthemum extract, or a bamboo leaf extract because the target derivative is stably maintained by an antioxidant action.

Vegetable oils used for extraction include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil , Sesame oil, wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil, etc. In addition, it is more preferable to use a vegetable oil containing a pine leaf extract, a kokushi extract, a green tea extract, a chrysanthemum extract, or a bamboo leaf extract because the intended derivative is stably maintained.

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

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

When isoflavone derivatives are obtained from these raw materials by biochemical enzymatic reaction, enzymes that cause an ester bond reaction such as lipase AY “Amano” 30G, lipase G “Amano” 50, lipase F-AP15 manufactured by Amano Enzyme. Neurase F3G and the like are used.

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 into a reaction tank, and the reaction is performed together with the organic solvent. It is preferable to extract this reaction product using the above-mentioned organic solvent and remove the solvent to obtain a crude product, because the cost required for purification can be reduced.

The target isoflavone derivative can be obtained by extracting from a natural material using the organic solvent or vegetable oil and further purifying it. Natural materials include plants such as black fig fruit or red clover flowers or leaf stems or seeds, seaweed, mushrooms, edible animals, edible fish, molluscs, insects, crustaceans and the like. In particular, black fig fruits or red clover flowers or leaf stems or seeds, edible fish heads and eel heads are characterized by their high content and 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 using the organic solvent or vegetable oil as a raw material is preferable because the waste is effectively used and the amount of waste is reduced.

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

The fermentation is performed by adding the microorganism or yeast to a fermentation base such as black fig fruit or red clover flower or leaf stem or seed, edible fish, edible fish head or internal organs, soybean or milk, etc. Implemented. After the fermentation, the desired isoflavone derivative can be obtained from the mixture of the microorganism or yeast and the fermentation broth using the organic solvent or vegetable oil.

When extracted from plants, black figs or red clover flowers, seeds, fruits and berries, roots, leaves, stems and other plants, green tea, garlic garlic, onions, garlic, soybeans, scallops, licorice, vermicelli, barley leaves, barley leaves, Kuzu Flower, Pepper, Oyster, Pear, Chestnut, Cod, Horseradish, Bracken, Rice, Wheat, Corn, Radish, Rape, Cherry, Pine, Aoki, Akane, Akamegashiwa, Akebi, Amachizuzuru, Amadokoroe, Aloe, Ikarisou, Itadori, Wild boar, Ibukizasou, Ukogi, Moray eel, Udo, Ume, Vulture, Ebisu, Ouren, Plantain, Okera, Okra, Hypericum, Onamomi, Ominae, Oyster, Cranberry, Alaskanae Leopard, Catalpa, Yellowfin, Yellow-billed, Goldworm, Horsetail, Horsetail, Kuzu, Gardenia, Kohonone, Kobushi, Pikachi, Soybean, Sartorii Rose Bucket, Sanshuyu, Janohige, Silane, Honeysuckle, Seri, Assembly, Tamushiba , Crocodile carrot, azalea, tochinoki, tochibanin ginseng, nanten, green rose, chickweed, pearl barley, scallops, baboon, cypress, hithitoba, loquat, fuki, fukujusou, fuji, matatabi, swordfish, yam, cypress Leaves, stems, flowers, fruits or roots are preferred because they are easily available.

Of these, the black fig is the scientific name Ficus Carica and is a tree widely distributed in South America, the Middle East, Africa, Japan, and the Chinese continent. The fruits of the black figs used here may be from any production area. The fruits of the black figs used are oval.

Black figs are preferred because they have abundant food experience and can stably supply the desired isoflavone derivative.

Among them, red clover is the scientific name Trifolium platen, is a perennial herb that is native to Europe and widely distributed in Europe, South America, the Middle East, Africa, Japan, and the Chinese mainland. Also known as red clover or purple clover. The red clover used here may be any place.

Red clover flowers and leaves are preferable because they have abundant food experience and can stably supply the target isoflavone derivative.

The fat-soluble isoflavone derivative is extracted with the organic solvent or vegetable oil. That is, as vegetable oil, palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, Oils used in edible or cosmetic products such as sesame oil, wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil Used,

In addition, it is more preferable to use a vegetable oil containing persimmon leaf extract, kokushi extract, green tea extract, chrysanthemum extract or pine leaf extract because the target derivative is stably maintained.

Further, for the separation of the target isoflavone derivative, it is preferable to use a purification operation such as a separation resin. In the case of separation, the organic solvent and vegetable oil described above are used, and the pine needle extract-containing vegetable oil is used in the crude purification stage, so that the antioxidant and antiseptic effects of the pine needle extract are exhibited, and the target derivative is obtained. It is preferable because it is stably maintained.

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

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

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

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

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

When the 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 suspended in a solvent for swelling the carrier for separation or the resin before separation. The amount is preferably 1 to 40 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 60 ° C., more preferably 15 to 50 ° C., from the viewpoint of the stability of the substance.

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

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

After collecting the separated fraction, it is preferable to remove the solvent by drying or vacuum drying to obtain the desired isoflavone derivative as a powder or a concentrated liquid because the influence of the solvent can be excluded.

The isoflavone derivative is obtained as a liquid or a powder. The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools and the like.

As a pharmaceutical, it is used for endometriosis therapeutic agent, osteoporosis therapeutic agent, dementia ameliorating agent, anticancer agent, wrinkle removing agent, prevention and improvement of menstrual pain. In addition, it is also used as a veterinary medicine used for animals and a medicine used for pets as a treatment for endometriosis, a treatment for osteoporosis, an anticancer agent, and the like.

The food preparation is used as a supplement, beverage, noodles, seasoning for the purpose of prevention or improvement in the case of feeling abnormalities in the uterus or mammary gland. Used for supplements for the purpose of improvement, prevention of sagging and improvement.
Furthermore, veterinary foods and food preparations used for animals, and food preparations used for pets are also used as pet supplements and pet foods for the purpose of improving fractures, preventing cancer, and promoting pregnancy.

The cosmetics are used as wrinkles, skin activation, cosmetics for improving skin regeneration, quasi drugs and massage oils. It is also used as cosmetics, quasi-drugs and massage oils that eliminate or prevent acne due to abnormal estrogen. It is also used as a veterinary cosmetic used for animals and a cosmetic used for pets.

The aforementioned pharmaceuticals, foods and cosmetics exhibit excellent therapeutic or preventive action against estrogen abnormalities and skin diseases derived therefrom. It is also used for clothing intended to remove fat using the fiber added with the isoflavone derivative, and particularly used for underwear, stockings, underwear, swimwear, socks, pajamas, futons and sheets.

Further, the plastics added with the isoflavone derivative are used for containers, toilets, baths and the like for the purpose of regulating estrogen.

Next, by adding palmitic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, the mixture is heated and extracted with vegetable oil. Among these isoflavone derivatives, X and Y are hydrogen, and Z is palmitic acid. An isoflavone derivative represented by the following formula (2) having an estrogen regulating action will be described.

The isoflavone derivative here is the above-described isoflavone derivative, and among them, X and Y are hydrogen, and hence formonetin derivatives. Since Z is palmitic acid, the isoflavone derivative here is palmitoylformonetin.

Among the above-mentioned isoflavone derivatives, when X is hydrogen and Y is hydrogen, this is a derivative in which a carboxylic acid of palmitic acid is ester-bonded to an isoisoflavone serving as a skeleton.

The isoflavone derivative exhibits an estrogen regulating action, suppresses excess of estrogen, and exhibits an estrogenic action when estrogen is reduced.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as an estrogen receptor in a nucleus in a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, in a state where estrogen is depleted or decreased, for example, in the case of menopause, estrogen is deficient. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue.

Since the isoflavone derivative has a structure with high fat solubility, it easily penetrates into the tissue and has an advantage that the amount exhibits at least an estrogen regulating action.

Furthermore, since it is decomposed by esterase existing locally to become isoflavones and fatty acids, the action is not sustained and safety is high.

Estrogen also has an important function in the brain. That is, protection of nerve cells. In other words, dementia tends to occur at menopause.

Since the isoflavone derivative has high fat solubility, it easily passes through the blood-brain barrier and works to protect brain neurons. However, since the excess amount is degraded by the esterase in the brain, there are few side effects due to the excess.

The isoflavone derivative is obtained by adding palmitic acid and a transesterified lipase to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating and extracting with vegetable oil.

Black fig fruits or red clover flowers or leaf stems or seeds are used as raw materials. Each production area may be any.

Among these, it is preferable that the use history of agricultural chemicals can be traced, the quality is stable, and the price is low.

Black fig fruits or red clover flowers or leaf stems or seeds can be either fresh or dried.

The collected black fig fruit or red clover flower or leaf stem or seed is preferably washed with tap water.

Black fig fruits or red clover flowers or leaf stems or seeds are ground. A pulverizer is used for pulverization. For example, a free mill, super free mill, sample mill, goblin, super clean mill, micros manufactured by Nara Machinery Co., Ltd., a small vacuum dryer manufactured by Toyo Riko as a vacuum dryer, stock A compact decompression heat transfer dryer DPTH-40 manufactured by Matsui Co., Ltd., clean dry VD-7, VD-20 manufactured by AKM Kyushu Technos Co., Ltd., etc. are used.

Palmitic acid used here is obtained from coconut oil, vegetable oil, rapeseed oil, cottonseed oil, corn oil, safflower oil, sesame oil, rice oil, sunflower oil, olive oil, etc., such as Ryoshoku, Nisshin Oil and Fuji Oil Co., Ltd. What was extracted and refine | purified from plants, such as a palm and a soybean, is preferable from there being few impurities.

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

The black fig fruit or red clover flower or leaf stem or seed pulverized product, palmitic acid and transesterification lipase 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 palmitic acid is preferably 0.02 to 2 weights and the transesterification lipase is preferably 0.0001 to 0.08 weights with respect to 1 weight of the crushed product of black fig fruit or red clover flower or leaf stem or seed to be added. .

As said heating temperature, 10-42 degreeC is preferable and 18-39 degreeC is more preferable.

The heating time is preferably 2 to 48 hours, more preferably 6 to 28 hours.

The heating is preferably performed while stirring, and a rate of 40 to 140 times per minute is preferable.

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

The produced fat-soluble isoflavone derivative is extracted with vegetable oil. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil , Wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil, and other oils used for food or cosmetics are used ,

In addition, it is more preferable to use a vegetable oil containing persimmon leaf extract, kokushi extract, green tea extract, chrysanthemum extract or pine leaf extract because the target derivative is stably maintained.

Among these, pine needle extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding vegetable oil to pulverized pine needles. Can be separated.

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

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

The vegetable oil to be added is preferably 0.4 to 4 weights per 1 weight of the pulverized product of black fig fruit or red clover flower or leaf stem or seed to be added.

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

Separating and purifying the target isoflavone 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 an appropriate separation solvent and remove the solvent to obtain the desired isoflavone derivative.

The isoflavone derivative thus obtained is obtained as a liquid or a powder.

The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools, clothing, fibers, plastics and the like.

The isoflavone derivative is obtained as a liquid or a powder. The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools and the like.

As a pharmaceutical, it is used for endometriosis therapeutic agent, osteoporosis therapeutic agent, dementia ameliorating agent, anticancer agent, wrinkle removing agent, prevention and improvement of menstrual pain. In addition, it is also used as a veterinary medicine used for animals and a medicine used for pets as a treatment for endometriosis, a treatment for osteoporosis, an anticancer agent, and the like.

The food preparation is used as a supplement, beverage, noodles, seasoning for the purpose of prevention or improvement in the case of abnormality in the uterus or mammary gland, and is also used for menstrual pain, irregular bleeding, genital cancer, wrinkles. Used for supplements for the purpose of improvement, prevention of sagging and improvement.

Furthermore, veterinary foods and food preparations used for animals, and food preparations used for pets are also used in the form of pet supplements and pet foods for the purpose of improving fractures, preventing cancer, and promoting pregnancy.

The cosmetics are used as wrinkles, skin activation, cosmetics for improving skin regeneration, quasi drugs and massage oils. It is also used as cosmetics, quasi-drugs and massage oils that eliminate or prevent acne due to abnormal estrogen. It is also used as a veterinary cosmetic used for animals and a cosmetic used for pets.

The aforementioned pharmaceuticals, foods and cosmetics exhibit excellent therapeutic or preventive action against estrogen abnormalities and skin diseases derived therefrom. It is also used for clothing intended to remove fat using the fiber added with the isoflavone derivative, and particularly used for underwear, stockings, underwear, swimwear, socks, pajamas, futons and sheets.

Further, the plastics added with the isoflavone derivative are used for containers, toilets, baths and the like for the purpose of regulating estrogen.

Next, in the above formula (1) obtained by adding eicosapentaenoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating and extracting with vegetable oil Among the isoflavone derivatives shown, an isoflavone derivative represented by the following formula (3) having an estrogen regulating action in which X and Y are hydrogen and Z is eicosapentaenoic acid will be described.

The isoflavone derivative here is the above-described isoflavone derivative, and among them, X and Y are hydrogen, and hence formonetin derivatives. Since Z is eicosapentaenoic acid, the isoflavone derivative here is eicosapentaenylformonetin.

Among the above-mentioned isoflavone derivatives, when X is hydrogen and Y is hydrogen, this is a derivative in which a carboxylic acid of eicosapentaenoic acid is ester-bonded to an isoisoflavone serving as a skeleton.

The isoflavone derivative exhibits an estrogen regulating action, suppresses excess of estrogen, and exhibits an estrogenic action when estrogen is reduced.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as an estrogen receptor in a nucleus in a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, in a state where estrogen is depleted or decreased, for example, in the case of menopause, estrogen is deficient. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue.

Since the isoflavone derivative has a structure with high fat solubility, it easily penetrates into the tissue and has an advantage that the amount exhibits at least an estrogen regulating action. Moreover, since the eicosapentaenyl group which is the side chain of eicosapentaenoic acid has an anti-inflammatory action by suppressing inflammatory cytokine and inflammatory prostaglandin, it is more preferable.

Furthermore, since it is decomposed by esterase existing locally to become isoflavones and fatty acids, the action is not sustained and safety is high.

Estrogen also has an important function in the brain. That is, protection of nerve cells. In other words, dementia tends to occur at menopause.

Since the isoflavone derivative has high fat solubility, it easily passes through the blood-brain barrier and works to protect brain neurons. However, since the excess amount is degraded by the esterase in the brain, there are few side effects due to the excess.

The isoflavone derivative can be obtained by adding eicosapentaenoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating, and extracting with vegetable oil.

Black fig fruits or red clover flowers or leaf stems or seeds are used as raw materials. Each production area may be any.

Among these, it is preferable that the use history of agricultural chemicals can be traced, the quality is stable, and the price is low.

Black fig fruits or red clover flowers or leaf stems or seeds can be either fresh or dried.

The collected black fig fruit or red clover flower or leaf stem or seed is preferably washed with tap water.

Black fig fruits or red clover flowers or leaf stems or seeds are ground. A pulverizer is used for pulverization. For example, a free mill, super free mill, sample mill, goblin, super clean mill, micros manufactured by Nara Machinery Co., Ltd., a small vacuum dryer manufactured by Toyo Riko as a vacuum dryer, stock A compact decompression heat transfer dryer DPTH-40 manufactured by Matsui Co., Ltd., clean dry VD-7, VD-20 manufactured by AKM Kyushu Technos Co., Ltd., etc. are used.

The eicosapentaenoic acid used here is obtained from edible fish oil, marine plankton, cultured microorganisms, etc., extracted and purified from edible fish such as Japanese fishery, Yaizu fishery and Toyo fishery, and has few impurities This is preferable.

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

The black fig fruit or red clover flower or leaf stem or seed pulverized product, eicosapentaenoic acid and transesterification lipase 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.

Eicosapentaenoic acid is preferably 0.01 to 3 wt. Per 1 wt. Of the black fig fruit or red clover flower or leaf stem or seed pulverized product, and the transesterification lipase is 0.0002 to 0.09 wt. preferable.

As said heating temperature, 12-44 degreeC is preferable and 20-38 degreeC is more preferable.

The heating time is preferably 2 to 48 hours, more preferably 4 to 28 hours.

The heating is preferably performed while stirring, and a rate of 35 to 150 times per minute is preferable.

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

The produced fat-soluble isoflavone derivative is extracted with vegetable oil. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil , Wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil, and other oils used for food or cosmetics are used ,

In addition, it is more preferable to use a vegetable oil containing persimmon leaf extract, kokushi extract, green tea extract, chrysanthemum extract or pine leaf extract because the target derivative is stably maintained.

Among these, pine needle extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding vegetable oil to pulverized pine needles. Can be separated.

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

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

The vegetable oil to be added is preferably 0.3 to 5 weights with respect to 1 weight of the pulverized product of black fig fruit or red clover flower or leaf stem or seed to be added.

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

Separating and purifying the target isoflavone 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 an appropriate separation solvent and remove the solvent to obtain the desired isoflavone derivative.

The isoflavone derivative thus obtained is obtained as a liquid or a powder.

The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools, clothing, fibers, plastics and the like.

The isoflavone derivative is obtained as a liquid or a powder. The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools and the like.

As a pharmaceutical, it is used for endometriosis therapeutic agent, osteoporosis therapeutic agent, dementia ameliorating agent, anticancer agent, wrinkle removing agent, prevention and improvement of menstrual pain. In addition, it is also used as a veterinary medicine used for animals and a medicine used for pets as a treatment for endometriosis, a treatment for osteoporosis, an anticancer agent, and the like.

The food preparation is used as a supplement, beverage, noodles, seasoning for the purpose of prevention or improvement in the case of abnormality in the uterus or mammary gland, and is also used for menstrual pain, irregular bleeding, genital cancer, wrinkles. Used for supplements for the purpose of improvement, prevention of sagging and improvement.

Furthermore, veterinary foods and food preparations used for animals, and food preparations used for pets are also used in the form of pet supplements and pet foods for the purpose of improving fractures, preventing cancer, and promoting pregnancy.

The cosmetics are used as wrinkles, skin activation, cosmetics for improving skin regeneration, quasi drugs and massage oils. It is also used as cosmetics, quasi-drugs and massage oils that eliminate or prevent acne due to abnormal estrogen. It is also used as a veterinary cosmetic used for animals and a cosmetic used for pets.

The aforementioned pharmaceuticals, foods and cosmetics exhibit excellent therapeutic or preventive action against estrogen abnormalities and skin diseases derived therefrom. It is also used for clothing intended to remove fat using the fiber added with the isoflavone derivative, and particularly used for underwear, stockings, underwear, swimwear, socks, pajamas, futons and sheets.

Further, the plastics added with the isoflavone derivative are used for containers, toilets, baths and the like for the purpose of regulating estrogen.

Next, docosahexaenoic acid and lipase for transesterification are added to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heated, extracted with vegetable oil, and expressed by the above formula (1). Among the isoflavone derivatives described above, an isoflavone derivative represented by the following formula (4) having an estrogen regulating action in which X and Y are hydrogen and Z is docosahexaenoic acid will be described.

The isoflavone derivative here is the above-described isoflavone derivative, and among them, X and Y are hydrogen, and hence formonetin derivatives. Since Z is docosahexaenoic acid, the isoflavone derivative here is docosahexaenylformonetin.

Among the above-mentioned isoflavone derivatives, when X is hydrogen and Y is hydrogen, it is a derivative in which a carboxylic acid of docosahexaenoic acid is ester-bonded to a skeleton isoisoflavone.

The isoflavone derivative exhibits an estrogen regulating action, suppresses excess of estrogen, and exhibits an estrogenic action when estrogen is reduced.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as an estrogen receptor in a nucleus in a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, in a state where estrogen is depleted or decreased, for example, in the case of menopause, estrogen is deficient. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue.

Since the isoflavone derivative has a structure with high fat solubility, it easily penetrates into the tissue and has an advantage that the amount exhibits at least an estrogen regulating action. Moreover, since the docosahexaenyl group which is a side chain of eicosapentaenoic acid has an anti-inflammatory action by suppressing inflammatory cytokine and inflammatory prostaglandin, it is more preferable.

Furthermore, since it is decomposed by esterase existing locally to become isoflavones and fatty acids, the action is not sustained and safety is high.

Estrogen also has an important function in the brain. That is, protection of nerve cells. In other words, dementia tends to occur at menopause.

Since the isoflavone derivative has high fat solubility, it easily passes through the blood-brain barrier and works to protect brain neurons. However, since the excess amount is degraded by the esterase in the brain, there are few side effects due to the excess.

The isoflavone derivative is obtained by adding docosahexaenoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating and extracting with vegetable oil.

Black fig fruits or red clover flowers or leaf stems or seeds are used as raw materials. Each production area may be any.

Among these, it is preferable that the use history of agricultural chemicals can be traced, the quality is stable, and the price is low.

Black fig fruits or red clover flowers or leaf stems or seeds can be either fresh or dried.

The collected black fig fruit or red clover flower or leaf stem or seed is preferably washed with tap water.

Black fig fruits or red clover flowers or leaf stems or seeds are ground. A pulverizer is used for pulverization. For example, a free mill, super free mill, sample mill, goblin, super clean mill, micros manufactured by Nara Machinery Co., Ltd., a small vacuum dryer manufactured by Toyo Riko as a vacuum dryer, stock A compact decompression heat transfer dryer DPTH-40 manufactured by Matsui Co., Ltd., clean dry VD-7, VD-20 manufactured by AKM Kyushu Technos Co., Ltd., etc. are used.

Docosahexaenoic acid used here is obtained from edible fish oil, marine plankton, cultured microorganisms, etc., extracted from edible fish such as Japan Fisheries, Yaizu Fisheries and Toyo Suisan, and is purified with little impurities. To preferred.

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

The above-described black fig fruit or red clover flower or leaf stem or seed pulverized product, docosahexaenoic acid and transesterification lipase 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.

Docosahexaenoic acid is preferably 0.02 to 4% by weight, and transesterification lipase is preferably 0.0001 to 0.08% by weight based on 1 weight of black fig fruit or red clover flower or leaf stem or seed pulverized product to be added. .

As said heating temperature, 10-46 degreeC is preferable and 16-39 degreeC is more preferable.

The heating time is preferably 3 to 50 hours, more preferably 6 to 29 hours.

The heating is preferably performed while stirring, and a rate of 38 to 190 times per minute is preferable.

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

The produced fat-soluble isoflavone derivative is extracted with vegetable oil. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil , Wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil, and other oils used for food or cosmetics are used ,

In addition, it is more preferable to use a vegetable oil containing persimmon leaf extract, kokushi extract, green tea extract, chrysanthemum extract or pine leaf extract because the target derivative is stably maintained.

Among these, pine needle extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding vegetable oil to pulverized pine needles. Can be separated.

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

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

The vegetable oil to be added is preferably 0.3 to 5 weights with respect to 1 weight of the pulverized product of black fig fruit or red clover flower or leaf stem or seed to be added.

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

Separating and purifying the target isoflavone 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 an appropriate separation solvent and remove the solvent to obtain the desired isoflavone derivative.

The isoflavone derivative thus obtained is obtained as a liquid or a powder.

The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools, clothing, fibers, plastics and the like.

The isoflavone derivative is obtained as a liquid or a powder. The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools and the like.

As a pharmaceutical, it is used for endometriosis therapeutic agent, osteoporosis therapeutic agent, dementia ameliorating agent, anticancer agent, wrinkle removing agent, prevention and improvement of menstrual pain. In addition, it is also used as a veterinary medicine used for animals and a medicine used for pets as a treatment for endometriosis, a treatment for osteoporosis, an anticancer agent, and the like.

The food preparation is used as a supplement, beverage, noodles, seasoning for the purpose of prevention or improvement in the case of abnormality in the uterus or mammary gland, and is also used for menstrual pain, irregular bleeding, genital cancer, wrinkles. Used for supplements for the purpose of improvement, prevention of sagging and improvement.

Furthermore, veterinary foods and food preparations used for animals, and food preparations used for pets are also used in the form of pet supplements and pet foods for the purpose of improving fractures, preventing cancer, and promoting pregnancy.

The cosmetics are used as wrinkles, skin activation, cosmetics for improving skin regeneration, quasi drugs and massage oils. It is also used as cosmetics, quasi-drugs and massage oils that eliminate or prevent acne due to abnormal estrogen. It is also used as a veterinary cosmetic used for animals and a cosmetic used for pets.

The aforementioned pharmaceuticals, foods and cosmetics exhibit excellent therapeutic or preventive action against estrogen abnormalities and skin diseases derived therefrom. It is also used for clothing intended to remove fat using the fiber added with the isoflavone derivative, and particularly used for underwear, stockings, underwear, swimwear, socks, pajamas, futons and sheets.

Further, the plastics added with the isoflavone derivative are used for containers, toilets, baths and the like for the purpose of regulating estrogen.

Next, benzoic acid and lipase for transesterification are added to black fig fruit or red clover flower or leaf stem or seed pulverized product, heated, extracted with vegetable oil, and expressed by the above formula (1). Among these isoflavone derivatives, X and Y are hydrogen, and Z is benzoic acid. An isoflavone derivative represented by the following formula (5) having an estrogen regulating action will be described.

The isoflavone derivative here is the above-described isoflavone derivative, and among them, X and Y are hydrogen, and hence formonetin derivatives. Z is benzoic acid.

Among the above-mentioned isoflavone derivatives, when X is hydrogen and Y is hydrogen, this is a derivative in which a carboxylate of benzoic acid is ester-bonded to an isoisoflavone serving as a skeleton.

The isoflavone derivative exhibits an estrogen regulating action, suppresses excess of estrogen, and exhibits an estrogenic action when estrogen is reduced.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as an estrogen receptor in a nucleus in a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, in a state where estrogen is depleted or decreased, for example, in the case of menopause, estrogen is deficient. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue.

Since the isoflavone derivative has a structure with high fat solubility, it easily penetrates into the tissue and has an advantage that the amount exhibits at least an estrogen regulating action. Further, the benzene group which is a side chain of benzoic acid exhibits an antibacterial action and an antioxidative action, so that it is effective since it also exhibits an effect even when there is an oxidative disorder when it is accompanied by bacterial infection. .

Furthermore, since it is decomposed by esterase existing locally to become isoflavone and benzoic acid, the action is not sustained and the safety is high.

Estrogen also has an important function in the brain. That is, protection of nerve cells. In other words, dementia tends to occur at menopause.

Since the isoflavone derivative has high fat solubility, it easily passes through the blood-brain barrier and works to protect brain neurons. However, since the excess amount is degraded by the esterase in the brain, there are few side effects due to the excess.

The isoflavone derivative is obtained by adding benzoic acid and lipase for transesterification to a ground product of black fig fruit or red clover flower or leaf stem or seed, heating, and extracting with vegetable oil.

Black fig fruits or red clover flowers or leaf stems or seeds are used as raw materials. Each production area may be any.

Among these, it is preferable that the use history of agricultural chemicals can be traced, the quality is stable, and the price is low.

Black fig fruits or red clover flowers or leaf stems or seeds can be either fresh or dried.

The collected black fig fruit or red clover flower or leaf stem or seed is preferably washed with tap water.

Black fig fruits or red clover flowers or leaf stems or seeds are ground. A pulverizer is used for pulverization. For example, a free mill, super free mill, sample mill, goblin, super clean mill, micros manufactured by Nara Machinery Co., Ltd., a small vacuum dryer manufactured by Toyo Riko as a vacuum dryer, stock A compact decompression heat transfer dryer DPTH-40 manufactured by Matsui Co., Ltd., clean dry VD-7, VD-20 manufactured by AKM Kyushu Technos Co., Ltd., etc. are used.

The benzoic acid used here is preferably obtained from a plant, a cultured microorganism or the like and purified, since it 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 Meisho Sangyo, or a lipase AY “Amano” manufactured by Amano Enzyme. High quality products such as 30G, lipase G “Amano” 50, lipase F-AP15, and neurase F3G are used, and these are preferable because their safety has been confirmed.

The black fig fruit or red clover flower or leaf stem or seed pulverized product, benzoic acid and transesterification lipase 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.

Benzoic acid is preferably 0.01 to 5 weights, and transesterification lipase is preferably 0.0001 to 0.07 weights with respect to 1 weight of black fig fruit or red clover flower or leaf stem or seed pulverized product to be added. .

The heating temperature is preferably 13 to 48 ° C, more preferably 20 to 38 ° C.

The heating time is preferably 4 to 56 hours, more preferably 8 to 27 hours.

The heating is preferably performed while stirring, and a rate of 40 to 180 times per minute is preferable.

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

The produced fat-soluble isoflavone derivative is extracted with vegetable oil. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil , Wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil, and other oils used for food or cosmetics are used ,

In addition, it is more preferable to use a vegetable oil containing persimmon leaf extract, kokushi extract, green tea extract, chrysanthemum extract or pine leaf extract because the target derivative is stably maintained.

Among these, pine needle extract-containing vegetable oil is a vegetable oil having an excellent antioxidative action and containing an oil-soluble polyphenol extracted by adding vegetable oil to pulverized pine needles. Can be separated.

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

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

The vegetable oil to be added is preferably 0.4 to 6 weights with respect to 1 weight of the pulverized product of black fig fruit or red clover flower or leaf stem or seed to be added.

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

Separating and purifying the target isoflavone 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 an appropriate separation solvent and remove the solvent to obtain the desired isoflavone derivative.

The isoflavone derivative thus obtained is obtained as a liquid or a powder.

The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools, clothing, fibers, plastics and the like.

The isoflavone derivative is obtained as a liquid or a powder. The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools and the like.

As a pharmaceutical, it is used for endometriosis therapeutic agent, osteoporosis therapeutic agent, dementia ameliorating agent, anticancer agent, wrinkle removing agent, prevention and improvement of menstrual pain. In addition, it is also used as a veterinary medicine used for animals and a medicine used for pets as a treatment for endometriosis, a treatment for osteoporosis, an anticancer agent, and the like.

The food preparation is used as a supplement, beverage, noodles, seasoning for the purpose of prevention or improvement in the case of abnormality in the uterus or mammary gland, and is also used for menstrual pain, irregular bleeding, genital cancer, wrinkles. Used for supplements for the purpose of improvement, prevention of sagging and improvement.

Furthermore, veterinary foods and food preparations used for animals, and food preparations used for pets are also used in the form of pet supplements and pet foods for the purpose of improving fractures, preventing cancer, and promoting pregnancy.

The cosmetics are used as wrinkles, skin activation, cosmetics for improving skin regeneration, quasi drugs and massage oils. It is also used as cosmetics, quasi-drugs and massage oils that eliminate or prevent acne due to abnormal estrogen. It is also used as a veterinary cosmetic used for animals and a cosmetic used for pets.

The aforementioned pharmaceuticals, foods and cosmetics exhibit excellent therapeutic or preventive action against estrogen abnormalities and skin diseases derived therefrom. It is also used for clothing intended to remove fat using the fiber added with the isoflavone derivative, and particularly used for underwear, stockings, underwear, swimwear, socks, pajamas, futons and sheets.

Further, the plastics added with the isoflavone derivative are used for containers, toilets, baths and the like for the purpose of regulating estrogen.

Next, an isoflavone derivative having an estrogen-regulating action obtained by extracting a fermented product obtained by adding fermented natto to fermented fish, black fig fruit or red clover flower or leaf stem or seed and soybean and fermenting them with vegetable oil To do.

The isoflavone derivative having an estrogen regulating action here is the aforementioned isoflavone derivative.

That is, the isoflavone skeleton has any one selected from hydrogen or a hydroxyl group and palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid. It is a bound derivative.

The above isoflavone derivatives are soluble in fat by binding any one of palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid. As a result, the structure of the isoflavone derivative is stabilized, and the estrogen regulating action is superior to that of isoflavone alone.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as an estrogen receptor in a nucleus in a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, in a state where estrogen is depleted or decreased, for example, in the case of menopause, estrogen is deficient. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue. That is, since it has a high fat-soluble structure, it has the advantage that it easily penetrates into the inside of the tissue and the amount exhibits at least an estrogen regulating action. In addition, since it is decomposed by locally existing esterase to become isoflavone and fatty acid, the action is not sustained and safety is high.

Estrogen also has an important function in the brain. That is, protection of nerve cells. In other words, dementia tends to develop due to the menopause.

Since the isoflavone derivative has high fat solubility, it easily passes through the blood-brain barrier and works to protect brain neurons. However, since the excess amount is degraded by the esterase in the brain, there are few side effects due to the excess.

The isoflavone derivative is any one selected from palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid having high fat-soluble characteristics. Because one is bound, it is easier to adapt to the cell membranes of the small intestine and skin than is isoflavone and is easily absorbed by the body.

If the isoflavone derivative is ingested and absorbed in excess, the excess amount is decomposed by the esterase in the blood, and each isoflavone and each palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearin Since it is decomposed into any of acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid, and the safety of each is confirmed, the above isoflavone derivatives are also highly safe.

Among the above isoflavone derivatives, when X is hydrogen and Y is hydrogen, the target isoflavone derivative is a formononetin derivative because the isoflavone serving as the skeleton is formononetin.

Of the above isoflavone derivatives, when X is hydrogen and Y is a hydroxyl group, the skeleton isoflavone is biocanin A, so the target derivative is biocanin A derivative.

Among the above isoflavone derivatives, when X is a hydroxyl group and Y is hydrogen, the skeleton isoflavone is 2'-hydroxyformononetin, so the target derivative is a 2'-hydroxyformononetin derivative. is there.

Among the above isoflavone derivatives, when X is a hydroxyl group and Y is a hydroxyl group, the skeleton isoflavone is 2′-hydroxybiocanin A, so the target derivative is a 2′-hydroxybiocanin A derivative. is there.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is palmitic acid, saturated fatty acid residues of palmitic acid easily penetrate into the cell membrane and are absorbed into the cell, enhancing the estrogen regulating action. Is preferable.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is eicosapentaenoic acid, the unsaturated fatty acid residue of eicosapentaenoic acid exhibits a suppressive action on the production of inflammatory cytokines and inflammatory prostaglandins. From the above, it is preferable because the estrogen regulating action is stably exhibited while suppressing the inflammatory action. In particular, it is more preferable because it suppresses the expression of interleukin 6 that is highly painful and induces osteoporosis.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is docosahexaenoic acid, the unsaturated fatty acid residue of docosahexaenoic acid exhibits inflammatory prostaglandin production inhibitory action, thus suppressing the inflammatory action. However, it is preferable because it exerts an estrogen regulating action.

Among the above isoflavone derivatives, when X and Y are hydrogen or hydroxyl group and Z is benzoic acid, the residue of benzoic acid exhibits antibacterial action, so that estrogen regulation is achieved while suppressing bacterial infection at the inflammatory site It is preferable because of its action.

Among the above-mentioned isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is capric acid, the fatty acid residue of capric acid penetrates the cell membrane and is easily absorbed into the cell, thereby enhancing the estrogen regulating action. This is preferable.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is stearic acid, the saturated fatty acid residue of stearic acid easily penetrates into the cell membrane and is absorbed into the cell, enhancing the estrogen regulating action. Is preferable.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is gamma-linolenic acid, unsaturated saturated fatty acid residues of gamma-linolenic acid penetrate into the cell membrane and are easily absorbed into the cell, This is preferable because the estrogen regulating action is enhanced.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is docosapentaenoic acid, the unsaturated fatty acid residue of docosapentaenoic acid exhibits an inflammatory prostaglandin production inhibitory action, This is preferable because the estrogen regulating action is stably exhibited while suppressing the inflammatory action.

Among the above isoflavone derivatives, when X and Y are hydrogen or a hydroxyl group and Z is alpha-lipoic acid, the fatty acid residue of alpha-lipoic acid exhibits an antioxidant action, thereby suppressing the oxidation of inflamed tissues. The estrogen regulating action is preferable since it is stably exhibited.

The isoflavone derivative is obtained by extracting a fermented product obtained by adding fermented natto to fermented fish, black fig fruit or red clover flower or leaf stem or seed and soybean and fermenting them with vegetable oil. As used herein, edible fish refers to fish used for food, and among them, eels have abundant food experience.

Eel heads and internal organs are preferred because they have dietary experience and contain various fatty acids and antioxidant components.

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 Technical Research Institute.

Black fig fruits or red clover flowers or leaf stems or seeds are 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 amount of each addition related to the fermentation is preferably 0.02 to 0.4 weight for black fig fruit or red clover flower or leaf stem or seed, and 0.1 to 3 weight weight for soybean relative to 1 weight of edible fish. The natto bacteria are preferably 0.001 to 0.03 weight.

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 30-48 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.

The isoflavone derivative produced by the fermentation is extracted with vegetable oil. Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil , Wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil, etc. In addition, it is more preferable to use a vegetable oil containing persimmon leaf extract, kokushi extract, green tea extract, chrysanthemum extract or pine leaf extract because the target derivative is stably maintained.

The above chrysanthemum flower extract-containing vegetable oil is a vegetable oil with an excellent anti-oxidation effect containing an oil-soluble polyphenol extracted by adding vegetable oil to the ground product of chrysanthemum flowers and stably separating the desired derivative. it can.

The pine leaves used in the chrysanthemum flower extract-containing vegetable oil can be used from any of Japan, China and Taiwan.

Chrysanthemum flowers cultivated without using pesticides are preferred because they can avoid the dangers caused by pesticides.

The above-mentioned pine leaf extract-containing vegetable oil is a vegetable oil having an excellent antioxidative effect and containing an oil-soluble polyphenol extracted by adding a vegetable oil to a pulverized pine leaf and stably separating a target derivative. it can.

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

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

The addition amount of the pine needle extract-containing vegetable oil 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 pine leaf extract-containing vegetable oil separated in the upper layer and remove the water. In order to remove moisture, a dryer such as TGD-250LF2 manufactured by Toyo Giken is used.

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

Separating and purifying the target isoflavone 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 obtain the desired isoflavone derivative by separation with an appropriate separation solvent, purification, and removal of the organic solvent.

As the solvent for separation, methanol, ethanol, chloroform, hexane, ethyl acetate, benzene, ether, and the like are used. Of these, ethanol for food processing or ethanol containing water is preferable because of its high use range.

The isoflavone derivative thus obtained is obtained as a liquid or a powder.

The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools, clothing, fibers, plastics and the like.

The isoflavone derivative is obtained as a liquid or a powder. The obtained isoflavone derivative is used for pharmaceuticals, food preparations, cosmetics, hygiene tools and the like.

As a pharmaceutical, it is used for endometriosis therapeutic agent, osteoporosis therapeutic agent, dementia ameliorating agent, anticancer agent, wrinkle removing agent, prevention and improvement of menstrual pain. In addition, it is also used as a veterinary medicine used for animals and a medicine used for pets as a treatment for endometriosis, a treatment for osteoporosis, an anticancer agent, and the like.

The food preparation is used as a supplement, beverage, noodles, seasoning for the purpose of prevention or improvement in the case of abnormality in the uterus or mammary gland, and is also used for menstrual pain, irregular bleeding, genital cancer, wrinkles. Used for supplements for the purpose of improvement, prevention of sagging and improvement.

Furthermore, veterinary foods and food preparations used for animals, and food preparations used for pets are also used in the form of pet supplements and pet foods for the purpose of improving fractures, preventing cancer, and promoting pregnancy.

The cosmetics are used as wrinkles, skin activation, cosmetics for improving skin regeneration, quasi drugs and massage oils. It is also used as cosmetics, quasi-drugs and massage oils that eliminate or prevent acne due to abnormal estrogen. It is also used as a veterinary cosmetic used for animals and a cosmetic used for pets.

The aforementioned pharmaceuticals, foods and cosmetics exhibit excellent therapeutic or preventive action against estrogen abnormalities and skin diseases derived therefrom. It is also used for clothing intended to remove fat using the fiber added with the isoflavone derivative, and particularly used for underwear, stockings, underwear, swimwear, socks, pajamas, futons and sheets.

Further, the plastics added with the isoflavone derivative are used for containers, toilets, baths and the like for the purpose of regulating estrogen.

Next, a composition containing 0.01 to 0.5 weight of chrysanthemum flower extract-containing vegetable oil and 0.01 to 0.5 weight of vegetable oil containing pine needle extract in 1 weight of the isoflavone derivative having the estrogen regulating action. A food preparation comprising:

The isoflavone derivative having an estrogen-regulating action here may be any of a crude product, a mixture, a synthesized product, a high-purity substance extracted with an organic solvent or vegetable oil, and purified. , A derivative in which any one selected from palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid is bound to isoflavone.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as an estrogen receptor in a nucleus in a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, in a state where estrogen is depleted or decreased, for example, in the case of menopause, estrogen is deficient. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue. That is, since it has a high fat-soluble structure, it has the advantage that it easily penetrates into the inside of the tissue and the amount exhibits at least an estrogen regulating action. In addition, since it is decomposed by locally existing esterase to become isoflavone and fatty acid, the action is not sustained and safety is high.

Estrogen also has an important function in the brain. That is, protection of nerve cells. In other words, dementia is likely to occur in menopausal women.

The isoflavone derivative is effective for dementia caused by estrogen deficiency by regulating estrogen action.

The isoflavone derivative is any one selected from palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid having high fat-soluble characteristics. Since one is bonded, it is easy to fit into the cell membranes of the small intestine and skin, and is easily absorbed.

The chrysanthemum flower extract-containing vegetable oil here is a vegetable oil having an excellent antioxidant effect obtained by extracting a ground chrysanthemum flower with a vegetable oil.

Vegetable oils include palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil, grape seed oil, and sesame oil , Wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil, and other oils used for food or cosmetics are used ,

Anri Japan's chrysanthemum flower extract-containing vegetable oil is preferred because of its high quality and low impurities.

The pine leaf extract-containing vegetable oil is obtained by pulverizing pine leaves from Japan, China, and Asia with a pulverizer and extracting them with vegetable oil.

Processed raw materials of pine leaves with cellulase such as Onozuka R-10, Y-NC manufactured by Yakult Pharmaceutical Co., Ltd., Cellulase A “Amano” 3 and Cellulase T “Amano” 4 manufactured by Amano Enzyme Co., Ltd. This is preferable because the extraction efficiency is improved.

The added chrysanthemum flower extract-containing vegetable oil is 0.01-0.5 wt. And the pine needle extract-containing vegetable oil is 0.01-0.5 wt. Per 1 wt.% Of the isoflavone derivative having estrogen regulating action. This gives a composition.

When the weight of the chrysanthemum flower extract-containing vegetable oil is less than 0.01 weight with respect to 1 weight of the isoflavone derivative, the target composition may not be sufficiently obtained.

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

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

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

In order to obtain the said composition, it is preferable to heat after mixing. As heating conditions, the temperature is 28 to 46 ° C., and the heating time is 6 to 49 hours.

When the heating temperature is lower than 28 ° C, there is a possibility that sufficient reaction may not occur. When the heating temperature is higher than 46 ° C., the reaction product generated by oxidation may turn brown. When the heating time is less than 6 hours, a sufficient product may not be obtained. When the heating time exceeds 49 hours, the product produced by oxidation may polymerize or turn brown.

This composition is preferable because the isoflavone derivative is continuously released little by little and becomes a continuous composition.

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

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. When the daily intake is less than 0.2 g, there is a possibility that sufficient estrogen regulating action is not 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 here refers to animal feed, pet supplements, and pet foods in addition to foods eaten by humans such as health functional foods, health supplements, general foods, and hospital foods used in hospitals.

The food preparations obtained here are used for the purpose of prevention or improvement when abnormalities are felt in the uterus or mammary gland, and as supplements, beverages, noodles, and seasonings. It is used as a supplement for the purpose of preventing or improving cancer, inflammation, osteoporosis, skin wrinkles, sagging.

Furthermore, veterinary foods and food preparations used for animals, and food preparations used for pets are also used in the form of pet supplements and pet foods for the purpose of improving fractures, preventing cancer, and promoting pregnancy.

Next, a composition containing 0.05 to 0.8 weight of chrysanthemum flower extract-containing vegetable oil and 0.05 to 0.8 weight of pine leaf extract-containing vegetable oil in 1 weight of the isoflavone derivative having the estrogen regulating action A cosmetic product consisting of

The isoflavone derivative having an estrogen-regulating action here may be any of a crude product, a mixture, a synthesized product, and a high-purity substance that has been extracted and purified. The isoflavone derivative includes isoflavone and palmitic acid. Any one selected from eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid and alpha-lipoic acid.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as an estrogen receptor in a nucleus in a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, in a state where estrogen is depleted or decreased, for example, in the case of menopause, estrogen is deficient. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue. That is, since it has a high fat-soluble structure, it has the advantage that it easily penetrates into the inside of the tissue and the amount exhibits at least an estrogen regulating action. In addition, since it is decomposed by locally existing esterase to become isoflavone and fatty acid, the action is not sustained and safety is high.

Estrogen also has an important function in the brain. That is, protection of nerve cells. In other words, dementia tends to develop due to the menopause.

The isoflavone derivative is effective for dementia caused by estrogen deficiency by regulating estrogen action.

The isoflavone derivative is any one selected from palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid having high fat-soluble characteristics. Since one is bonded, it is easy to fit into the cell membranes of the small intestine and skin, and is easily absorbed.

The chrysanthemum flower extract-containing vegetable oil here is an oil obtained by adding vegetable oil to a ground product of chrysanthemum flowers and extracting it, and has an excellent antioxidant effect.

As vegetable oil used here, vegetable oil includes palm oil, palm oil, soybean oil, olive oil, rapeseed oil, rice oil, germ oil, corn oil, safflower oil, linseed oil, almond oil, sesame oil, cacao oil, canola oil. , Grape seed oil, sesame oil, wheat germ oil, rice bran oil, safflower oil, perilla oil, tea oil, camellia oil, pumpkin seed oil, peanut oil, grape oil, hazelnut oil, cottonseed oil, peanut oil, etc. In addition, the use of a vegetable oil containing persimmon leaf extract, kokushi extract, green tea extract, chrysanthemum extract, pine leaf extract, etc. further stabilizes the target derivative. preferable.

Anri Japan's chrysanthemum flower extract-containing vegetable oil is preferred because of its high quality and low impurities.

The pine leaf extract-containing vegetable oil is obtained by pulverizing pine leaves from Japan, China, and Asia with a pulverizer and extracting them with vegetable oil.

Processed raw material of pine leaves with cellulase such as Onozuka R-10, Y-NC manufactured by Yakult Pharmaceutical Co., Ltd., Cellulase A “Amano” 3 and Cellulase T “Amano” 4 manufactured by Amano Enzyme Co., Ltd. This is preferable because the extraction efficiency is improved.

Chrysanthemum flower extract-containing vegetable oil is added in an amount of 0.05 to 0.8 weight, and pine needle extract-containing vegetable oil is added in an amount of 0.05 to 0.8 weight based on 1 weight of the isoflavone derivative having an estrogen regulating action. This gives a composition.

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

If the weight of the chrysanthemum flower extract-containing vegetable oil is more than 0.8 weight relative to 1 weight of the isoflavone derivative, the solubility of the isoflavone derivative may be reduced and may precipitate.

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

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

In order to obtain the said composition, it is preferable to heat after mixing. As heating conditions, the temperature is 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 isoflavone derivative is continuously released little by little and becomes a continuous composition.

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

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

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

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

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

Cosmetics are used as wrinkles, skin activation, cosmetics that improve skin regeneration, quasi drugs and massage oils. In addition, it is used as cosmetics, quasi-drugs and massage oils that eliminate or prevent acne caused by estrogen and physiological abnormalities. It is also used as a veterinary cosmetic used for animals and a cosmetic used for pets.

Next, the therapeutic agent for endometriosis comprising the isoflavone derivative having the estrogen regulating action will be described.

The isoflavone derivative having an estrogen-regulating action here may be any of a crude product, a mixture, a synthesized product, and a high-purity substance that has been extracted and purified. The isoflavone derivative includes isoflavone and palmitic acid. Any one selected from eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid and alpha-lipoic acid.

The isoflavone derivative exhibits an estrogen regulating action by modifying an estrogen receptor such as an estrogen receptor in a nucleus in a cell.

That is, when the estrogen is excessive and the estrogen receptor reacts excessively, the isoflavone derivative antagonizes the estrogen receptor and suppresses the estrogen action to normalize.

For example, in the case of endometriosis, the action of estrogen causes ectopic endometrial tissue to react and proliferate the tissue and release inflammatory materials. The result is endometriosis with pain.

The isoflavone derivative modifies the estrogen receptor to improve endometriosis by inhibiting excessive endometrial tissue proliferation and inflammation by estrogen.

On the other hand, in a state where estrogen is depleted or decreased, for example, in the case of menopause, estrogen is deficient. Estrogens are normal and have the effect of building bone tissue. Estrogen deficiency causes bone tissue to weaken and induce osteoporosis.

The isoflavone derivative protects bone tissue by expressing an estrogen-like action in the menopausal state where estrogen is reduced. That is, the isoflavone derivative reacts with an estrogen receptor to act like estrogen and protect bone tissue. That is, since it has a high fat-soluble structure, it has the advantage that it easily penetrates into the inside of the tissue and the amount exhibits at least an estrogen regulating action. In addition, since it is decomposed by locally existing esterase to become isoflavone and fatty acid, the action is not sustained and safety is high.

The isoflavone derivative is any one selected from palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid having high fat-soluble characteristics. Since one is bonded, it has the feature that it is easily adapted to and absorbed by the cell membrane of the small intestine and skin.

When used as a pharmaceutical, it is necessary to remove the influence of impurities, and therefore it is preferable to use an isoflavone 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 therapeutic agent for endometriosis here is a pharmaceutical product for improving endometriosis. In endometriosis, ectopic uterine tissue is disseminated in the body due to hormonal abnormalities, or metastasizes into the abdominal cavity. In particular, the tissue grows due to estrogen, and abnormal bleeding causes pain. It is also one of the causes of infertility.

In addition, it can be used as a veterinary medicine for the purpose of improving obesity and fat accumulation in livestock and pets.

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

First, an isoflavone derivative exhibiting an estrogen regulating action obtained by fermentation will be described.

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

The collected head and internal organs of 1.4 kg were cut with a knife and pulverized with DM-6 manufactured by Nakayama Technical Research Institute.

This was put into a clean culture tank, and 2.6 L of tap water was added. After washing 1.4 kg of red clover flowers collected in Shizuoka Prefecture cultivated without agricultural chemicals with tap water, it was dried with a dryer (Nishimura Kikai Co., Ltd., GZQ3 type). And crushed. 200 g of this pulverized product was added to the above cylinder. To this, Chinese soybean was washed with water, then heated to 60 ° C. for 90 minutes and ground to obtain 1.4 kg of ground soybean.

To this, 14 g of natto bacteria manufactured by Natto Motopo was added. Fermentation was continued for 39 hours at a temperature of 38 ° C. with stirring.

To the tank where the fermentation was completed, 3.4 L of tap water was added and stirred to make a fermented product.

1 kg of RIKEN vitamin palm oil was added to the fermented product, and the mixture was stirred for 3 hours and mixed.

The oil-soluble part separated by the palm oil which left this still and isolate | separated into the upper layer was extract | collected as a liquid. In order to remove moisture, it was subjected to a dryer (TGD-250LF2 manufactured by Toyo Giken) to obtain the desired isoflavone derivative as an oily substance. This was used as the sample of Example 1.

The following describes the preparation of isoflavone derivatives covalently bound to palmitic acid.

1 kg of Aichi-made black figs grown with no pesticides was purchased, washed thoroughly with tap water, and dried with a dryer.

1 kg of the dried black fig fruit was subjected to a pulverizer (manufactured by Sanriki Seisakusho Co., Ltd., a three-purpose universal pulverizer) and pulverized to obtain a pulverized product of black fig fruit.

1 kg of crushed black fig fruit was put into a clean cylinder and 8 L of tap water was added. To this, 210 g of palmitic acid purchased from Ryoshoku was added and stirred.

To this was added 10 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 37 ° C. and stirred at a rate of 69 times / minute for 12 hours to obtain a heated solution.

After cooling the cylinder containing the warming solution with tap water, 1.4 kg of RIKEN vitamin palm oil was added, and the oil portion was collected.

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

The preparation of an isoflavone derivative to which eicosapentaenoic acid is bound is described below.

3 kg of Chinese red clover flowers grown without pesticides were collected, washed thoroughly with tap water, and dried with a dryer. 2.4 kg of this red clover flower was subjected to a crusher (manufactured by Sanriki Seisakusho Co., Ltd., a three-purpose universal crusher) and pulverized to obtain a pulverized product of red clover flower.

1.8 kg of tap water was added to 1.8 kg of crushed red clover flowers in a clean cylinder. To this, 250 g of Eicosapentaenoic acid manufactured by Nippon Suisan was added and stirred.

To this was added 18 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 33 ° C. and stirred at a rate of 63 times / minute for 12 hours to obtain a heated solution.

After cooling the cylinder containing the warming liquid with tap water, 1 kg of Ajinomoto 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 an isoflavone derivative to which eicosapentaenoic acid was bound as an oily liquid. This was also used as the sample of Example 3.

The following describes the preparation of an isoflavone derivative to which docosahexaenoic acid is bound.

2.8 kg of Chinese black figs grown without pesticides was collected, washed thoroughly with tap water, and dried with a dryer (Nishimura Kikai, GZQ3 type). This was the fruit of the raw black fig.

The black fig fruit 2.7 kg was subjected to a pulverizer (manufactured by Sanriki Seisakusho Co., Ltd., a three-purpose universal pulverizer) and pulverized to obtain a pulverized product of black fig fruit.

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

To this was added 12 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 28 ° C. and stirred at a rate of 70 times / minute for 13 hours to obtain a heated solution.

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

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

The preparation of an isoflavone derivative to which benzoic acid is bound is described below.

2.7 kg of Chinese black figs grown without pesticides was collected, washed thoroughly with tap water, and dried with a dryer (Nishimura Kikai, GZQ3 type). This was the fruit of the raw black fig.

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

1.2 kg of ground figs of black figs were put into a clean cylinder and 12 L of tap water was added. To this, 260 g of benzoic acid, which is a food additive made by Iwai Chemical, was added and stirred.

To this was added 12 g of lipase AY “Amano” 30G manufactured by Amano Enzyme, and the mixture was heated to 30 ° C. and stirred at a rate of 66 times / minute for 14 hours to obtain a heated solution.

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

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

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

100 g of the isoflavone derivative obtained in Example 2 was suspended in 500 mL of ethanol and applied to a column packed with 800 g of Diaion made by Mitsubishi Chemical. This was washed with 800 mL of water containing 5% ethanol. Further, after washing with 900 mL of water containing 20% ethanol, elution was performed with 900 mL of water containing 50% ethanol, and then a fraction of water containing 90% ethanol was collected.

This fraction was subjected to a vacuum dryer to distill off ethanol and water, and then 20 g of a purified product of isoflavone derivative was obtained by a freeze dryer manufactured by Nippon FD. This was used as the sample of Example 6.

Below, the identification test of an isoflavone derivative is demonstrated.
(Test Example 1)

Each isoflavone derivative 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 a high-speed mass spectrometer was provided. Analysis was performed by liquid chromatography (HPLC, Shimadzu Corporation), and analysis was further performed by a nuclear magnetic resonance apparatus (NMR, manufactured by Bruker, AC-250).

As a result, from the sample of Example 1, isoflavone as isoflavone derivative was added palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, alpha-lipoic acid. Bound isoflavone derivatives were identified. Each carboxyl group and isoflavone were ester-bonded.

In addition, from the specimens of Example 2 and Example 6, isoflavone derivatives in which palmitic acid was bound to isoflavone were identified. The carboxylic acid of palmitic acid and the isoflavone were ester-bonded.

Further, from the sample of Example 3, an isoflavone derivative in which eicosapentaenoic acid was bound to isoflavone was identified. Eicosapentaenoic acid carboxylic acid and isoflavone were ester linked.

Further, from the sample of Example 4, an isoflavone derivative in which docosahexaenoic acid was bound to isoflavone was identified. The carboxylic acid of docosahexaenoic acid and isoflavone were ester-linked.

Further, from the sample of Example 5, an isoflavone derivative in which benzoic acid was bound to isoflavone was identified. The carboxyl group of benzoic acid and the isoflavone were ester-bonded.

Hereinafter, an estrogen-like test using osteoblasts will be described for the specimen.
(Test Example 2)
Osteoblasts obtained from healthy women were purchased from Kurabo Industries and used. 10,000 osteoblasts were seeded in a culture dish having a diameter of 35 mm. This was cultured at 37 ° C. for 2 days under 5% carbon dioxide gas. A MEM culture solution not containing phenol red was used as the culture solution. MEM broth was used as a solvent control.

To this, 0.1 mg / mL each of the specimens obtained in Examples 1 to 6 was added, and the number of osteoblasts was counted.

As a result, the number of cells 3 days after the sample addition obtained in Example 1, Example 2, Example 3, Example 4, Example 5, and Example 6 was compared to the value of the solvent control, They were 231%, 189%, 239%, 240%, 195% and 272%, respectively.

As a result, in the specimens obtained in Examples 1 to 6, the osteoblast proliferation effect was observed, and the estrogen action was confirmed.

The production of a food preparation containing an isoflavone derivative is described below.

100 g of the isoflavone derivative obtained in Example 1 was placed in a food processing mixer (Tsukasa, Pow mixer, single type), and 15 g of chrysanthemum flower extract-containing vegetable oil manufactured by Toyo Fermentation Co., Ltd. was added. To this, 15 g of pine leaf extract-containing soybean oil manufactured by Toyo Fermentation Co., Ltd. was added, and this was heated at 36 ° C. for 20 hours with stirring, and cooled to obtain about 120 g of a composition.

To 120 g of this composition, 300 g of edible cellulose, 1.1 g of ascorbic acid and 9 g of edible flavor 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 swine-derived gelatin hard capsules at a dose of 280 mg to obtain a food preparation. This was used as the sample of Example 7.

Below, the test of a food formulation is demonstrated.
(Test Example 3)
Using the food preparation obtained in Example 7, a bone density test was performed on 10 healthy women aged 54 to 70 years. That is, immediately after the end of menstruation, the food preparation obtained in Example 7 was ingested, and before and after ingestion, the bone density was examined by the DXA method.

That is, first, the bone density was measured in advance. Thereafter, 2 food preparations were taken once a day for 30 days. After the final intake, the bone density was measured in the same manner.

As a result, the bone density after ingesting the food preparation obtained in Example 7 was 142% in relative ratio as compared with before ingestion.

As a result, the food preparation obtained in Example 7 was confirmed to have an estrogen-like action that increases bone density when estrogen was reduced. No abnormalities were observed in the physical condition due to the intake of the food preparation.

30 g of the isoflavone derivative obtained in Example 2 was placed in a cosmetic processing mixer (Pole Container Mixer, manufactured by Kotobuki Industries Co., Ltd.), and 8 g of chrysanthemum flower extract-containing vegetable oil manufactured by Toyo Fermentation Co., Ltd. was added. To this, 20 g of pine leaf extract-containing soybean oil manufactured by Toyo Fermentation Co., Ltd. was added, and this was heated at 39 ° C. for 36 hours with stirring to obtain about 70 g of a composition.

This composition was put into the mixer, and 230 g of beeswax (manufactured by API) and 0.5 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 control cream excluding the isoflavone derivative obtained in Example 2 was prepared.

Below, the test example evaluated about the effect and side effect of cosmetics is shown.
(Test Example 4)
For 7 healthy women aged 55 to 69 years with wrinkles on the face, 1 g of the cream obtained in Example 8 was applied to the right half of the face, and a control cream consisting of only the base material was applied to the left half every day for 30 days. did. After the application for 30 days, the number of wrinkles (manufactured by Integral, shock wave measuring device, RVM600) was measured.

As a result, the number of wrinkles on the right half foot of the face to which the cream containing the isoflavone derivative was applied was 42% compared to the left half of the face to which only the base material was applied.

These results show that the cosmetic product of Example 8 reduces wrinkles.

Furthermore, no side effects were observed in the skin condition, physical condition, blood test, etc. by application of this cosmetic product, confirming safety.

Hereinafter, a therapeutic agent for endometriosis comprising an isoflavone derivative will be described.

Into a clean stainless steel dissolution tank, 20 g of the isoflavone derivative obtained in Example 6 above, 80 g of lanolin, 60 g of macrogold, 10 g of beeswax and 10 g of ozokerite were added and dissolved at 37 ° C. for 1 hour. This was supplied to a kneader and mixed. This was again dissolved in a dissolution tank, heated, and deaerated with a deaerator to obtain the intended endometriosis therapeutic agent as an ointment for specimen 9.

As a control, a control sample using lanolin instead of the isoflavone derivative obtained in Example 6 was prepared, and used as a control sample in the test.

The test using the endometriosis drug will be described below.
(Test Example 5)
A clinical trial using the aforementioned endometriosis drug was conducted. To 20 endometriosis patients, 1 g of the ointment obtained in Example 9 was applied to the abdomen and applied. The application was 1 g once a day, and was performed every day for 30 days.

A blood test was performed before application and 30 days after application, and the amount of interleukin-6 in the blood was measured. Interleukin-6 is a parameter of inflammation and increases with endometriosis.

As a result, the average value of interleukin-6 after 30 days of application was reduced to 39% compared with that before application. As a result, it was confirmed that the ointment of Example 9 exhibited an improvement effect on endometriosis.

On the other hand, no abnormalities were observed in subjective symptoms, blood test values, and other blood biochemical tests, and the safety of the endometriosis drug of Example 9 was confirmed.

In addition, in the ointment using only base materials, such as lanolin, the amount of interleukin-6 was 101% compared with the value before application | coating, and the change was not recognized.

The isoflavone derivative having an estrogen-regulating action of the present invention prevents and ameliorates diseases caused by an increase and decrease in estrogen such as endometriosis, uterine cancer, breast cancer, osteoporosis, dementia, and has weak side effects. Excellent work.

Moreover, the food formulation which consists of an isoflavone derivative which has the estrogen regulation effect | action which is this invention prevents the disease resulting from the increase and decrease of an estrogen, and contributes to the quality improvement of a national life.

Furthermore, a cosmetic product comprising an isoflavone derivative having an estrogen regulating action shows an improvement or prevention effect against wrinkles caused by estrogen reduction and improves the beauty industry.

In addition, according to the endometriosis therapeutic agent comprising an isoflavone derivative having an estrogen-regulating action, the endometriosis can be improved or prevented by reducing the estrogen action. This endometriosis drug has few side effects and exhibits an excellent estrogen regulating action, thereby contributing to the activation of the medical and pharmaceutical industries.

Black fig fruits or red clover flowers or leaf stems or seeds or the head or internal organs of 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 ocean 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)

An isoflavone derivative represented by the following formula (1) having an estrogen regulating action.

X is either hydrogen or a hydroxyl group.
Y is either hydrogen or a hydroxyl group.
Z is any one selected from palmitic acid, eicosapentaenoic acid, docosahexaenoic acid, benzoic acid, caprylic acid, stearic acid, gamma-linolenic acid, docosapentaenoic acid, and alpha-lipoic acid. The isoflavone derivative according to claim 1, obtained by adding palmitic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating, extracting with vegetable oil, An isoflavone derivative represented by the following formula (2) having an estrogen regulating action in which X and Y are hydrogen and Z is palmitic acid.

An eicosapentaenoic acid and lipase for transesterification are added to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heated, extracted with vegetable oil, and the isoflavone derivative of claim 1 Of these, an isoflavone derivative represented by the following formula (3) having an estrogen regulating action, wherein X and Y are hydrogen and Z is eicosapentaenoic acid.

The isoflavone derivative according to claim 1, obtained by adding docosahexaenoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating and extracting with vegetable oil, An isoflavone derivative represented by the following formula (4) having an estrogen regulating action in which X and Y are hydrogen and Z is docosahexaenoic acid.

The isoflavone derivative according to claim 1, which is obtained by adding benzoic acid and lipase for transesterification to a pulverized product of black fig fruit or red clover flower or leaf stem or seed, heating, extracting with vegetable oil, An isoflavone derivative represented by the following formula (5) having an estrogen regulating action, wherein X and Y are hydrogen and Z is benzoic acid.

2. An isoflavone having an estrogen-regulating action according to claim 1, obtained by extracting with a vegetable oil a fermented product obtained by adding fermented natto to fermented fish, black fig fruit or red clover flower or leaf stem or seed and soybean. Derivative. Claim 1 or claim 2 or claim 3 or claim 4 or claim 5 or claim 6 containing 1 to 1 weight of isoflavone derivative having an estrogen regulating action, chrysanthemum flower extract-containing vegetable oil 0.01 to 0.5 A food preparation comprising a composition containing 0.01 to 0.5 weight by weight of a pine needle extract-containing vegetable oil. Claim 1 or claim 2 or claim 3 or claim 4 or claim 5 or claim 6 containing 1 to 1 weight of isoflavone derivative having an estrogen regulating action, chrysanthemum flower extract-containing vegetable oil 0.05 to 0.8 Cosmetics comprising a composition containing 0.05 to 0.8 weight by weight of a pine needle extract-containing vegetable oil. A therapeutic agent for endometriosis comprising the isoflavone derivative having an estrogen-regulating action according to claim 1, claim 2, claim 3, claim 4, claim 5, or claim 6.