TW201238593A - Anti-inflammatory agent and process of producing same - Google Patents

Abstract

Provided is a material which is safe and inexpensive, can be ingested easily and continuously on a daily basis, and has a significant anti-inflammatory activity. An anti-inflammatory agent comprising a mixture of: a soybean seed or an extract thereof each of which has been activated by a light irradiation treatment and/or a heating treatment; and chlorophyll.

Description

201238593 VI. Description of the Invention: [Technical Field] The present invention relates to an anti-inflammatory agent, a method for producing the same, and a pharmaceutical, a cosmetic, a food or drink, a feed, and the like containing the anti-inflammatory agent. [Prior Art] Anti-inflammatory agents can be used for the treatment of inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and osteoarthritis, and hay fever, allergic rhinitis, allergic conjunctivitis and Inflammatory symptoms such as atopic dermatitis. As anti-inflammatory agents for pharmaceuticals, steroid-based anti-inflammatory drugs, non-m-alcoholic anti-inflammatory drugs, and immunosuppressive solutions are currently known. "Either of them has strong side effects, so there must be a problem that must be carefully administered under the guidance or management of the physician. On the other hand, attempts have also been made to replace these drugs, and the indications of anti-inflammatory effects are indicated by ingestion. Health foods, for example, health-care foods, etc., to improve inflammatory diseases or inflammatory symptoms, such as sweet tea, (iv) glycosamine, chondroitin, lycopene, catechin, etc., or foods added thereto. However, compared with medicine Although these health foods have fewer side effects, the improvement effect of inflammation is weaker and cannot be said to have sufficient anti-inflammatory effects. Therefore, it is expected to be developed for daily use, and it may be mild and inflammatory diseases or Anti-inflammatory agent for inflammatory symptoms. Dali has been known as a raw material for tofu, camp oil, natto, etc., and is trying to obtain functional ingredients from soybean seeds. For example, the special offer 1 reveals 101106175 £ 3 201238593 An anti-allergic composition, which uses stachyose as an active ingredient to improve ectopic! · Inflammation symptoms of dermatitis model animals, and records that stachyose can be ugly The amount of stachyose contained in the soy mover is very small, and only the extraction operation is not sufficient. Therefore, in order to concentrate it to more than 98% of the effect that can be surely encountered In addition, it is necessary to carry out a complicated purification step such as a chromatography method. The result is that the cost is too high. Further, since stachyose is indigestible, if it is ingested at a high concentration, there is a problem that a lower state occurs. On the one hand, chlorophyll is known as a molecule related to the energy production system of plants, and is also used as an additive component of foods or cosmetics. It is known that chlorophyll has a wound healing effect, a deodorizing effect, and a complement system for promoting granulation of ulcers and the like. Inhibition, etc. (Patent Document 2), but it is not known that a trace amount of chlorophyll contributes to the prevention of inflammation. (Patent Document 1) Japanese Laid-Open Patent Publication No. 2003-321372 (Patent Document 2) Japanese Patent Laid-Open Publication No. 2004-256423 SUMMARY OF THE INVENTION The present invention provides an anti-inflammatory agent comprising soybean seeds activated by light irradiation treatment and/or heat treatment or In addition, the present invention provides a method for producing an anti-inflammatory agent, which comprises the steps of obtaining a mixture of soybean seeds or an extract thereof and chlorophyll; and performing the compound of 101106175 201238593 The step of activating treatment by light irradiation and/or heating. Further, the present invention provides a method for enhancing the anti-inflammatory action of soybean, comprising: a step of obtaining a mixture of soybean seeds or an extract thereof and chlorophyll; The step of activating treatment by light irradiation and/or heating. The present invention provides a medicine, a cosmetic, a food or drink, and a feed, which comprise soybean seeds activated by light irradiation treatment and/or heat treatment or The mixture of the extract and chlorophyll. The present invention provides a use of a mixture of soybean seeds or an extract thereof and chlorophyll activated by light irradiation treatment and/or heat treatment in an anti-inflammatory agent. Furthermore, the present invention provides a method for treating an inflammatory disease, which comprises administering a mixture of soybean seeds activated by light irradiation treatment and/or heat treatment or an extract thereof and chlorophyll to a subject. [Embodiment] The present invention relates to a material of natural origin which is safe, inexpensive, and simple and continually ingested, and has a remarkable inflammatory inhibitory effect, and is effective for preventing and/or ameliorating various inflammatory diseases or inflammatory symptoms. The present inventors have diligently studied to solve the above problems, and as a result, it has been found that a composition obtained by activating a mixture of soybean seeds and chlorophyll by light irradiation and/or heating has superior macrophage activity. Inhibition of inhibition and inhibition of IL-2 production can be used for anti-inflammatory. According to the present invention, an anti-inflammatory agent is provided which is safe and inexpensive, and has a daily anti-inflammatory effect, and has an anti-inflammatory effect, and is effective for preventing and/or improving various inflammatory diseases and inflammatory symptoms. The anti-inflammatory agent of the present invention can be produced by obtaining a mixture of soybean seeds or an extract thereof and chlorophyll, and subjecting the mixture to light irradiation and/or heat activation. Accordingly, the present invention provides an anti-inflammatory agent comprising a mixture of soybean seeds or an extract thereof and chlorophyll which are activated by light irradiation treatment and/or heat treatment. Further, the present invention provides a method for producing an anti-inflammatory agent comprising the steps of: obtaining a mixture of soybean seeds or an extract thereof and chlorophyll; and activating treatment of light irradiation and/or heating of the mixture. Further, the present invention provides a use of a mixture of activated soybean seeds or an extract thereof and chlorophyll by photoirradiation treatment and/or heat treatment to produce an anti-inflammatory agent. For example, the anti-inflammatory agent of the present invention can reduce the production of IL-2 by tau cells as shown in the examples below. IL-2, which is a kind of interleukin, is also called inflammatory interleukin. It is produced by T cells or NK cells (natural killer cells) and has the proliferation of T cells, B cells, NK cells, macrophages, etc. And activation, the production of antibodies against B cells, and the enhanced function of cytotoxicity, as a result of local or systemic inflammatory symptoms, and various secondary symptoms induced by such, such as inflammatory skin Inflammatory diseases such as inflammation, gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and osteoarthritis, and hay fever, allergic rhinitis, allergies 101106175 6 201238593 Conjunctivitis and atopic dermatitis Wait for a variety of allergic symptoms. Therefore, the anti-inflammatory agent of the present invention can prevent, treat, ameliorate or alleviate the inflammatory symptoms caused by the disease caused by the disease. Further, for example, the anti-inflammatory agent of the present invention is as shown in the later embodiment.

The production caused by giant scorpion cells is reduced. The mega-cell line system kills and destroys various cytotoxic factors such as enzymes, active oxygen, and nitric oxide (10) by invading human pathogens while circulating I. It is known that the megatuber cell activation marker has a biological defense effect on the NO produced by NO production/activated python cells. : Aspects cause inflammation to worsen when excess occurs. Anti-inflammatory effects can be expected by suppressing the occurrence of additional mascara. Therefore, the inflammatory agent of the present invention exerts an anti-inflammatory action by inhibiting macrophage resistance. By recording and suppressing the production, the "anti-inflammatory" effect caused by the present invention is caused by the decrease of IL-4 or the resistance of the anti-inflammatory agent. Shouting prevention, treatment: ί: Alleviating the allergic diseases mentioned above, compared with the case of the type 11/V type allergic reaction caused by the allergic reaction: 1. The above allergic disease is atopic dermatitis The symptoms obtained by the anti-human agent of the present invention for prevention, treatment, improvement or alleviation include acupuncture or color

S-sinking leaks but does not include improving the symptoms of spasm caused by IgE. Further, for example, 101106175 201238593 includes symptoms of prevention, treatment, improvement or alleviation by the anti-inflammatory agent of the present invention, including pain, redness, heat sensation, and swelling which are four major symptoms of inflammation, but this does not include IgE is caused by vascular penetrating sputum caused by chemical media released by mast cells and the like. Therefore, in an exemplary embodiment, the anti-inflammatory agent of the present invention may be an inhibitor of IL-2 production, an inhibitor of megatubular cell activation, an inhibitor of NO production of megatuber cells, an allergic reaction of type II to V, A treatment, prevention, treatment, amelioration or alleviation agent for various inflammatory diseases, symptoms or conditions caused by IL-2 production or activation of megatuber cells. Examples of inflammatory diseases, symptoms, or conditions caused by the production of IL-2 include local or systemic inflammatory symptoms, and various secondary symptoms induced by such, for example, inflammatory dermatitis. , inflammatory diseases such as gastritis and ulcerative colitis, arthritis such as rheumatoid arthritis and osteoarthritis, and various types of hay fever, allergic rhinitis, allergic conjunctivitis, and atopic dermatitis. Inflammatory symptoms of allergic diseases. As an example of an inflammatory disease, symptom or state caused by activation of macrophages, for example, inflammation caused by NO produced by giant sputum cells is deteriorated. As shown in the examples below, the composition obtained by activating the light irradiation and/or heating of the mixture of the soybean seed or the extract thereof and the chlorophyll is compared with the light irradiation of the soybean extract and/or The heat treatment material has an enhanced anti-inflammatory activity. It is indicated that the anti-inflammatory action of soybean can be enhanced by obtaining a mixture of soybean seeds or an extract thereof and chlorophyll, and subjecting the mixture to light irradiation and/or heating activation 101106175 8 201238593. Accordingly, the present invention further provides a method for enhancing the anti-inflammatory action of soybean, comprising the steps of obtaining a mixture of soybean seeds or an extract thereof and chlorophyll, and the step of activating the mixture with light irradiation and/or heating. . In the present specification, 'so-called "soybean seed." means a mature seed of soybean (Glycine max). The soybean seed used in the present invention is not particularly limited in its variety. It is preferably a soybean that is most commonly eaten, such as Akishirome (certified No. No. 69) and Ayakogane (identified No. 114, No. 114). ), Iwaikuro (certified number Nonglin No. 'variety registration number 9796), Erustar (certified number Nonglin No. 115 'variety registration number 8864), Enrei (identification number Nonglin No. 57), Oosuzu (identification number Nonglin 109, variety registration No. 9795), 〇otsum (certification number Nonglin No. 91, variety registration number 2044), Okushirome (certification number Nonglin No. 59), Kariyutaka (identification number Nonglin No. 95, variety registration number No. 3293), Kitamusume (identification number Nonglin) No. 49), Ginrei (No. 1 No. 2, No. 5860, No. 5860), Kurodaruma (No. 128, No. I5130, No. I5130), K〇SUzu (No. 87, No. 87, Variety Registration No. 2397) No.), K〇t〇yutaka (identification number Nonglin No. 132, variety registration number 丨9477), Sachiyutaka (identification number Nonglin 116 , variety registration number U367), Sayanami (identification number Nonglin 1G4, variety registration number 8644 101106175 9 201238593), Suzumaru (identification number Nonglin No. 89 'variety registration number 2043), Suzukari (identification number Nonglin 83, variety Registration No. 1218), Suzukogane (identification number Nonglin I11, variety registration number 9793),

Suzukomachi (No. 119, No. 119, σσ, No. 12278), SUZUSayaka (No. 125, No. 1 No. 1404), Tachinagaha (No. 85, No. 1509, No. 1509), Tachihomare Nonglin No. 134, variety registration No. 19476), Tachiyutaka (No. No. 86, No. 1818, No. 1818), Tamahomare (No. 72, No. 201, No. 201), Tamaurara (No. 112, No. , variety registration number 1〇622), Jade black (identification number Nonglin No.1, No. 8835), Tamamasari (identification number Nonglin number, variety registration number 9792), Tanrei (identification number Nonglin No. 65) ), Zhongshengguang Black (10 963 'Hokkaido), TomoyUtaka (No. No. 92, No. 2878, No. 2878), T〇y〇k〇machi (No. 90, No. 2042, No. 2042) , Toyomusume or Toyomasari (identification number No. 81, No. 1216), Nakasennari (certified number, No. 66) Natto, Nanahomar e (variety registration number 20592)

Nishimusume (Certificate No. No. 93, No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. No. 122, No. 13191, No. 13191), 101106175 10 201238593

Fukuminori (variety registration number No. 24879), Fukuyutaka (certification number Nonglin No. 73, variety registration number No. 202), H〇nen (certification number Nonglin No. 105 'type registration number No. 8645), Miyagishirome (Iwanuma No. 1 'Miyagi Prefecture) ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, (Certificate No. No. 118, No. 12279, No. 12279), Yumeminori (No. 117, No. 129, No. 12280), Yuhou (No. 100, No. 5859, No. 5859) The above-mentioned "certification number" refers to the identification number of the certified agricultural and forestry products identified by the Ministry of Agriculture, Forestry and Fisheries of Japan, and the "variety registration number" refers to the species registration number registered according to the seedling method. These soybean varieties, Gongxun, can be searched by the variety registration data retrieval system of the Ministry of Agriculture, Forestry and Fisheries (www.hinsyu.maff.go.jp/). Or it is recorded in the "Characteristics of the Inland Water, Wheat, and Soybean Awards" (Ministry of Agriculture, Forestry and Fisheries Production Bureau, March, 2008) or "The Dictionary of Domestic Soybean Varieties 201" (Production and Distribution Promotion Section of the Production Bureau of the Ministry of Agriculture, Forestry and Fisheries, Heisei 23 years 2 months). The above "seed" includes seed coats and/or embryos, and the germline includes cotyledons and embryo-axes. Preferably, the seed is a peeled seed. In the present specification, the soy seed may be any form of soybean seed, such as large and seed (preferably peeled seed +) itself; the soybean seed is cut, pulverized or powdered; the large face is paid by the person The pea seed is dried or pulverized or pulverized after being dried at 101106175 201238593; the soybean seed is subjected to squeezing out 俨 '10 or its residue; or its form, suspension, suspension, and the like. Alternatively, the form of the soybean seed used in the present invention may include, for example, concentrated soy protein, soy whey produced by the soy milk, okara, and isolated soy protein, which is produced by the concentrated soybean egg from the material. Acid washing liquid scale washing = night, water immersion liquid of soybean produced by the production of tofu or soy milk. The soybean seed is used in any form according to the present invention, and is selected according to the required activity, cost, quality, degree of flavor as a stand, and the like. In the present invention, the extract of soy seeds refers to the juice extraction method by the above-mentioned listed ΓΓ seed, for example, soybean seed itself, or by cutting the soybean seed, drying the smash, and squeezing out the squeezing method. There is no particular limitation, and for example, it is possible to carry out a series of strokes in a solvent, and to prepare various kinds of soybean seeds. And a solvent preferred medium that can be used in supercritical fluid extraction. Specifically, it is a red alcohol = an organic solvent, more preferably a polar solvent, and a neutral one. As a lower alcohol such as organic dissolved tap water, acidic water, isopropanol or n-butanol, (di), n-propanol, oil Such as polyols and other liquids at room temperature: 3 · butanediol, propylene glycol, glyco-so), etc. These solvents can be used alone to make =, _ class; gas imitation, dimethyl yor above organic solvent In the case of the fall, it is also possible to combine two or more types. 101106175 For the brain of Sang Zuo Ling cut, it is better to use 201238593. The alcohol scale used for liquid to warm is more preferably ethanol. a lower alcohol of 1 to 4. - The content of the step containing the aqueous component is also included in the above-mentioned alcohol-based medium in the surface solvent. As the aqueous organic solvent, it is preferred to use an aqueous containing water-containing component. Alcohols; more preferred as an extraction solvent, water-alcohols, etc., among which A h and the above-mentioned water-containing right are water ethanol and aqueous ethanol. 31 d organic solvent in organic solvent: % or more Preferably, it is generally 6 to 50 liters and more than 80% by volume, more preferably the above The extraction volume of the seed is as above. The method of extracting under reduced pressure two: = mixing; in reflux in the solvent: m, method, etc. At this time, the extraction temperature is set to 5t to the temperature below the solvent point The appropriate extraction time depends on the type of solvent used or the extraction conditions, and in the case of an aqueous organic solvent, depending on the content of the aqueous component, 30 minutes to 72 hours or so. The low-phase solvent is used according to the extraction or extraction of the soybean seed, and the extraction operation can be carried out by supercritical fluid extraction using carbon dioxide or the like. The receiver will contain a mixture of the extract and the residue. If necessary, it is supplied to a filtration or centrifugation, etc. to remove the difficult-to-shoot components to obtain an extract. Further, the removed m-formation may be supplied to the extraction operation again. The operation may be further repeated 101106175 13 201238593. The extract thus obtained can be directly used in the present invention for the extract of the A rotor, and the secret surface-(4) can be made into a powder or a powder by a method of concentrating or collecting dry I (four) mist drying. And _, or _ is used as a powder, a paste or a paste. When the extract is dried, the specific drying method is a method for riding the soybean seed extracting secret or the age of the solution. Further, it may be any method, and for example, a method of adding a domain-shaped agent as needed, and performing filtration, centrifugation, centrifugal filtration, spray drying, spray cooling, drum drying, vacuum drying, Kangkang drying, etc. It can be used singly or in combination. In the present specification, as chlorophyll, it is not only limited to chlorophyll (chlorophyll a, chlorophyll b) contained in green plants, but also chlorophyll c chlorophyll c2, chlorophyll d or chlorophyllin contained in algae. The chlorophyll may be refined chlorophyll, or the plant or algae may be processed by a known method (for example, by pulverization or extraction, etc.) by means of chlorophyll. Further, those commercially available as reagents such as chlorophyll a and chlorophyll b (manufactured by SIGMA) can also be used. The mixture of the soybean seed of the present invention or the extract thereof and the chlorophyll may be a mixture obtained by mixing the soybean seed of any of the above forms or an extract thereof with the chlorophyll. As a preferable example of the mixture, for example, a mixture of a soybean extract and purified chlorophyll, a mixture of a soybean seed powder and a powder of a plant or an algae, and the like can be mentioned. The ratio of the soybean seed or the extract thereof to the chlorophyll in the mixture, for example, 101106175 201238593, such as the mass ratio of the soybean extract (dry solid mass) to the refined chlorophyll, if it is 50000]~1〇: i, Jia 2〇〇〇〇: Bu, for example, the powder of soybeans and the powder of the plant (four) _: (4) (7) can be a good face ^. The anti-inflammatory agent of the present invention can be produced by the activation treatment of the above mixture by light irradiation and/or heating. In the present invention, the "activation treatment" refers to a treatment in which the upper (tetra) compound is irradiated with light or heated to convert the active material precursor contained in the mixture into an active material. The "light" of the so-called "light" is not only limited to visible light, but also includes infrared light and ultraviolet light. For example, it can be 200nm~_nm, and the car is good 28〇nm~7〇〇 N, more preferably 36 〇 ~ 65 〇Μ ^ wavelength of light. The specific order of the system is not determined. (4) The light is irradiated according to the illuminance of the above mixture (the product of kilograms: kb〇 and irradiation time (10) is more than the above-mentioned ones. In the present specification, the heating system may be heated at a temperature of, for example, 40 to 1 Torr 5 Torr, preferably 7 Torr to 1 Torr, for a period of G. 5 hours to 144 hours, preferably 2 to 72 hours. The order is not particularly limited, and any heating means known in the art can be used. In the present document, in the case of combining the light irradiation treatment and the heat treatment, the above-described respective steps are performed simultaneously and/or sequentially according to the respective processing conditions described above. · It can be processed. If the combination of nuclear processing and addition and subtraction of silk (4) is required, the amount of processing may be 70106175 15 201238593. For example, light irradiation treatment and heating of 50% of each of the above-mentioned set amounts may be performed simultaneously or sequentially. Treatment, that is, light treatment of 2〇klx · hr or more and heat treatment of 0.25 hours or more, or light treatment of 50klx · hr or more and heat treatment of 1 hour or more, etc. Further, for example, light irradiation treatment and heat treatment may be used. 5% of the processing amount set as described above: the same as 95% to 95%: the same as 5%. Alternatively, the total processing of the light irradiation treatment and the heat treatment may exceed the processing amount set as described above. For example, it may be I00klx. a combination of light treatment of .hr or more and heat treatment of one day or more, etc. In the above order, a mixture of soybean seeds or an extract thereof and chlorophyll is obtained, and the mixture is subjected to light irradiation and/or heating activation treatment. The anti-inflammatory agent of the present invention can be produced. That is, the "activation treatment" means that the application of the above mixture is used to reduce the IL-2 production amount of the T cell to the mixture as compared with the case where it is not applied. 70% or less, preferably a treatment for reducing the amount of IL 2 produced to less than 6% by weight, more preferably 50% or less. Alternatively, the "activation treatment" means application by the above mixture, compared to the unapplied In this case, the mixture is subjected to a treatment for reducing the amount of NO produced by macrophages to 7 Å/( or less, preferably to reduce the production of N 至 to 60% or less, more preferably 5 8% or less. The anti-inflammatory agent of the invention is preferably The amount of IL_2 produced by the T cell is reduced to 7 G% or less, more preferably 6% or less, more preferably 5 Å/〇 or less when the preparation of the present invention is not administered. Or, the anti-inflammatory agent of the present invention is preferably made. The amount of N〇 produced by the giant cell is reduced to 70% or less, 101106175 201238593, more preferably 60% or less, still more preferably 50% or less, when the preparation of the present invention is not administered. The anti-inflammatory agent of the present invention is treated by light irradiation. And/or activated by heat treatment, containing a mixture of soybean seeds or an extract thereof and chlorophyll as an active ingredient. The anti-inflammatory agent of the present invention comprises substantially only the mixture. In an exemplary embodiment, The anti-inflammatory agent may be an inhibitor of IL-2 production, an inhibitor of macrophage activation, an inhibitor of NO production by macrophages, or a type II to V allergic reaction, IL-2 production or macrophage activation. Disposal, prevention, treatment, amelioration or alleviation of various inflammatory diseases, symptoms or conditions. Soybean seed is used as a food for a long period of time, and its safety is confirmed. In addition, chlorophyll is also a commonly consumed ingredient in vegetables or algae. Therefore, the anti-inflammatory agent of the present invention which is used as a raw material has no side effects even if it is administered or ingested for a long period of time. It is not only a healthy person or an adult, but can be safely and continuously carried out for children, elderly people and those who are ill. Invest or ingest. Further, chlorophyll is decomposed to become pheophorbide, which is known to be harmful to health. If a large amount of chlorophyll containing magnesium chlorophyll acid is ingested, problems will occur. However, since the anti-inflammatory agent of the present invention is activated by chlorophyll, the content of chlorophyll is small, and therefore there is no doubt that a large amount of magnesium chlorophyll is taken up even if the anti-inflammatory agent of the present invention is administered or ingested. Therefore, a mixture of soybean seeds or an extract thereof and chlorophyll activated by the above-described light irradiation treatment and/or heat treatment (hereinafter referred to as an activated compound 101106175 17 201238593) can be used as a medicine for human or animal use. , cosmetics, food and beverage, feed, etc., or used to make this. Accordingly, the present invention also provides a medicine, a cosmetic, a food or drink, and a feed containing the above-described activated mixture. The medicine, cosmetics, food and drink, and feed can be used for various inflammatory diseases, symptoms, or conditions caused by anti-inflammatory, inhibition of IL-2 production, inhibition of macrophage activation, or production of IL_2 or activation of macrophages. Prevent, treat, improve or alleviate. The medicine of the present invention may be an anti-inflammatory [IL-2 production inhibitor] containing a mixture of the above active quinones as an active ingredient; an inhibitor of megatubular cell activation; or various inflammations caused by IL-2 production of sensitization Prevention, treatment, amelioration or palliative of a disease, symptom or condition. Examples of the dosage form of the present invention include a surfactant, a capsule, a granule, a powder, a syrup, a dry sugar preparation, a liquid preparation, a suspension agent, and the like; an inhalant, a suppository, etc. Enteral preparation; drip; injection; topical agent, transdermal, transmucosal, nasal spray; inhaled drug; patch. Further, a liquid preparation such as a liquid preparation or a suspension agent may be dissolved or suspended in water or other suitable medium immediately before administration, or in the case of a tablet or a granule, the surface may be known by a known method. Apply. A1 February: Make-up (10) is a form in which the above-mentioned activated mixture is contained as an effective finished product, and examples thereof include a cream, an emulsion, a lotion, (4) a gelatin, a powder, a mask, a powder tablet, a powder block, a powder stick, and a powder cake. . Hanging 101106175 201238593 The pharmaceutical and cosmetic of the present invention may contain the above-mentioned activated masks alone or may be combined with a carrier which is acceptable for the pharmaceutical and a carrier acceptable for the cosmetic. The pharmaceutical and cosmetic of the present invention may also be formulated with a conventional carrier such as an excipient, a disintegrant, a binding agent, a surfactant, a surfactant, a pH adjuster, and a dispersing agent in the above-mentioned active mixture. Emulsifiers, antiseptics, inter-oxidants, colorants, alcohols, water, water-soluble polymers, perfumes, M, materials, flavoring agents, sour materials, etc., are manufactured according to the f method. Depending on the f, you can also use other active ingredients or medicinal ingredients. The content of the above-mentioned activating mixture in the pharmaceuticals and cosmetics of the present invention varies depending on the dosage form, and is based on the amount of dry f, and is in the range of G to %, preferably 0.01 to 80% by mass. The food or drink of the present invention contains the above-mentioned active ingredient mixture, and is intended to achieve anti-inflammatory, IL-2 production inhibition, macrophage synthesis, or IL-2 production or macrophage activation. The effect of prevention, treatment, improvement, or mitigation of the diseases, symptoms, and conditions of the various diseases, such as health foods, functional foods and drinks, foods for specific health care, foods for patients, livestock, Pet food for horse racing, ornamental animals, etc. The form of the food and beverage and the feed of the present invention is not particularly limited, and includes all forms of the above-mentioned activating mixture. For example, as this form. I. The guar is semi-solid or liquid, or may be, for example, a key agent, a chew bond _, a 丨 丨 J J J, ^p· Φ, granules, a drink, a gel, a syrup, a liquid food sigma for transureal nutrition, etc. 101106175 19 201238593 Various forms. Examples of the form of the food and drink product, for example, tea beverages such as green tea, oolong tea or black tea, coffee drinks, refreshing drinks, fruit greens, sports drinks, milk drinks, carbonated drinks, fruit drinks, lactic acid bacteria drinks, Fermented milk beverages, powdered beverages, cocoa drinks, alcoholic beverages, refined water, etc., creams, fruit icing, spreading materials, milk marlin and other smears, beauty milk, oil, cassava sauce, dripping Sauces, breads, rice, noodles, pasta, miso soup, tofu, milk, yogurt, soup or sauce, snacks (such as soft cakes or; dry, chocolate, candy, cakes, ice cream) , chewing gum, chewing gum, etc. According to the present invention, the food can be used in accordance with the composition and form of the food and beverage, and the food is described in the book, and the feed can be similarly applied. The foods and beverages and feeds may be used in the above-mentioned activating mixture to prepare other food and beverage materials, various nutrients, various vitamins, minerals, amino acids, various fats and oils, various additives used in the manufacture of foods and beverages or feeds (for example). It is produced by a usual method, such as a taste component, a sweetener, an acid substance such as an organic acid, a surfactant, a pH adjuster, a stabilizer, an antioxidant, a coloring matter, and a seasoning. Alternatively, the food or drink or feed of the present invention can be produced by blending the above-mentioned active ingredient in a food or drink or a feed which is generally consumed. The content of the above-mentioned activating mixture in the food and drink and the feed of the present invention varies depending on the form of the food, and is usually from 0 001 to 80% by mass, preferably from 0.01 to 50% by mass, more preferably 1 based on the dry mass. ~50% by mass range. 101106175 20 201238593 The above-mentioned medicines, cosmetics, foods, and feeds are administered or ingested in an amount of 0.01 to 100 g per day per day based on the dry mass of the above-mentioned activating mixture. In the case of oral administration or ingestion, the daily dose is usually 0.1 to 50 g, but since the above-mentioned activating mixture has high safety, the amount thereof can be further increased. The above-mentioned daily administration or intake may be administered or ingested one time, and may be administered or ingested in several times. In order to appropriately administer or ingest the above-mentioned daily amount, it is preferred to use the pharmaceutical dosage form of the present invention or the form of the administration therapy, or the food or beverage and the feed as a manageable dosage or intake per meal. Type. Further, the present invention provides a use of the above-described activating mixture for treating, preventing, treating, ameliorating or alleviating an inflammatory disease. Alternatively, a method of treating, preventing, treating, ameliorating or alleviating an inflammatory disease comprising administering the above-described activating mixture to a subject is provided. Examples of the inflammatory disease include various inflammatory diseases, symptoms, or conditions caused by π-v plastic allergic reaction, IL-2 production, or macrophage activation. The preparation method of the above activated mixture is as described above. The subject to be administered may, for example, be a human or an animal having an inflammatory disease; a human or an animal that must be anti-inflammatory, inhibited by IL-2 production, inhibited activation of megatuber cells, or inhibited NO production by giant cell cells; Humans or animals that have to be treated, prevented, treated, ameliorated or alleviated by various inflammatory diseases, symptoms or symptoms caused by π-type-7 allergic reaction, IL-2 production or macrophage activation. Examples of inflammatory diseases, symptoms or conditions caused by IL-2 production 101106175 21 201238593, and examples of inflammatory diseases, symptoms or states caused by activation of megatuber cells are as described above. The administration route of the above activating mixture may be oral or parenteral. The amount of the active mixture to be administered is based on the dry mass, and may be in the range of 0.01 to 100 g per adult. The amount and method of administration may be appropriately determined by the practitioner depending on the state of the object. For example, the above-mentioned activating mixture can be administered to a subject once a day, twice a day, three times a day, two times a day, two times a day, or several days or more. (Examples) Hereinafter, the present invention will be described in more detail by way of Examples, but the present invention is not limited to the specific examples. (Examples 1 to 2) (1) 56 μg of water was added to 8 g of soybean powder (Fukuyutaka's Nishio Powder), and the mixture was heated at 85 to 90 ° C for 1 hour. The heat treatment liquid was dried by a spray dryer (Okawara processing mechanism L-8 type) to obtain 533 g of a powder. (2) 5 mL of ethanol was added to 10 g of the powder obtained in (1), and the mixture was stirred and extracted at 25 ° C and 300 rpm for 2 hours, and then filtered using a glass fiber filter paper (manufactured by Kirsai Seisakusho Co., Ltd.) to remove insoluble matter, and the ethanol extract was recovered. . Ethanol was distilled off, and a soybean extract of 230 mg (yield 2.3%) was obtained. (3) Next, 63 mg of the soybean extract was dissolved in 3 mL of ethanol. Chlorophyll (chlorophyll b: manufactured by SIGMA) 1 mg (1/60 mass ratio of soybean extract) was added thereto to seal the petri dish. Each of the culture dishes was subjected to activation treatment by irradiating light (300 rpm) while irradiating (300 rpm) at 25 ° C while irradiating light (zinc light: illuminance 2 klx/h). (4) After 3 days and 6 days after the start of light irradiation, 10 mL of the ethanol solution was recovered from the culture, and concentrated and dried to prepare Examples 1 and 2 (the yield of Example 1 was 26-7 mg, and the yield of Example 2: i5. 9mg). (Comparative Examples 1 to 2) The same procedures as in the steps (1) to (4) of Examples 1 to 2 were carried out, but in the step (3), chlorophyll was not added to prepare Comparative Examples 1 to 2 (production of Comparative Example 1) : 22.7 mg 'Production of Comparative Example 2 35.4 mg). (Comparative Example 3) According to the same procedure as in the step (2) of the Example 1 to 2, 63 mg of the obtained soybean extract was dissolved in 3 rnL of ethanol to obtain Comparative Example 3. (Comparative Examples 4 to 5) No soybean extract was added to 30 mL of ethanol, and only chlorophyll img was added. This was subjected to light treatment in the same manner as in the steps (3) to (4) of Examples 1 to 2, and as Comparative Example 4, the person who was not subjected to light treatment was referred to as Comparative Example 5. (Comparative Examples 6 to 7) 63 mg of the soybean extract obtained in the same manner as in the steps (1) to (2) of Examples 1 to 2 was placed in a petri dish, dissolved in 3 mL of ethanol, and then chlorophyll was added. (chlorophyll b: manufactured by SIGMA) 1 mg (1/60 by weight of soybean extract), and the petri dish was sealed with a lid. Stirring was carried out under 25 art and shading (3 〇 (kpm), 2 mL after 3 days and 6 days later, and concentrated to dryness, respectively, as comparison 101106175 23 201238593 Examples 6, 7 (Comparative Example 6 yield: 1.7 mg, comparison Yield of Example 7: 4.4 mg) (Examples 3 to 4) (1) 20 g of the soybean extract obtained in the same manner as in the step (2) of Examples 1 to 2 was placed in a flask, and the green juice was mixed. Powder (produced by Nisshin Pharma; chlorophyll content = 4 mg/g) 3 g (mass ratio of dry solid mass of stalk extract to chlorophyll = 1667: 1), dissolved in sterol U5mL, stirred at 40 ° C under light blocking (3〇〇i*pm) ' While performing heat treatment. (2) After 1 day and 3 days after the start of heating, 10 mL of the methanol solution was recovered from the beaker and concentrated to dryness, as Examples 3 and 4 (Example 3, respectively) Yield: 250.1 mg, yield of Example 4: 220.9 mg) 0 (Examples 5 to 6) (1) The same procedure as in the step (1) of Examples 3 to 4, except that the temperature was set to 75 ° C. Heat treatment was carried out. (2) After 1 day and 3 days after the start of heating, 10 mL of the methanol solution was recovered from the beaker and concentrated to dryness, as Example 5, respectively. 6 (production of Example 5: 210_8 mg, yield of Example 6: I80.4 mg) (Test Example 1: inhibition of NO production) Activation of macrophage-derived lipopolysaccharide (LPS) to enhance NO production The effects of the above-prepared samples (Examples 1 to 2 and Comparative Examples 1 to 7) on NO were investigated. RAW264.7 cells (DS Pharma Biomedical Co., Ltd.) were subcultured with 10% FCS + DMEM medium. The RAW264.7 fine 101106175 24 201238593 cells were prepared into 2χ105 cells/ml (10% FCS+DMEM medium) cell suspension, seeded in 24 wells per lmL, and cultured for 24 hours. The medium was exchanged to contain 500 ng/ The LPS of ml and the samples of various concentrations (Examples 1 to 2 and Comparative Examples 1 to 7) were cultured for 18 hours in 10% FCS + DMEM medium. As a control group, the medium was exchanged for LPS-free medium. At the same time, after the completion of the culture, NO released to the medium was derivatized as N〇2 ions for quantification. The N〇2 ion was quantified using a measurement kit (Griess Reagent System: Promega)' according to the instruction manual. , each sample is dissolved in DM SO was added to the medium at 0.2% by volume. The final concentrations were set to 0.05 mg/mL for Examples 1 to 6 and Comparative Examples 1 to 3 and 6 to 7, and Comparative Examples 4 to 5 were 0.0083 mg/mL (0.05 mg/mL). +60: Examples 1 to 2 were the same amount as the chlorophyll concentration). The results are shown in Figure 1 and Tables 1 and 2. Examples 1 to 2 obtained by subjecting the soybean extract to the chlorophyll compound to light irradiation treatment, and Examples 3 to 6 obtained by heat-treating the mixture of the soybean extract and the chlorophyll, significantly inhibited the giant rabbit. NO production by cells. On the other hand, in Comparative Examples 1 to 2 in which light treatment was performed only in the case of using only soybean extract, and Comparative Example 3 in which light treatment was not performed, N0 was not affected. Moreover, only the ratio of chlorophyll to Example 4 (with light treatment) and Comparative Example 5 (matte treatment) did not cause no noise. Further, the mixture of the soybean extract and the chlorophyll which were not subjected to the light irradiation treatment and the heat treatment (Comparative Examples 6 to 7) had a slight influence on the ?? 101106175 25 201238593 [Table i] Soybean extract chlorophyll light irradiation time illuminance X irradiation time fklx · hr) NO production amount f% VS control group) Example 1 + + 3曰2x72 43 3 Example 2 + + 6曰2x144 26 9 Comparative Example 1 + - 3 曰 2 x 72 87.3 Comparative Example 2 + - 6 曰 2 x 144 84.7 Comparative Example 3 + - One _ 95 4 Comparative Example 4 One + 6 曰 2 x 144 80.5 Comparative Example 5 One + — —. 85 4 Comparative Example 6 + + - .__ 71.1 Comparative Example 7 + + one - 75.7 [Table 2] Soybean extract chlorophyll heating time heating temperature (° 〇 NO production amount (% vs control group) Example 3 + + 1 曰 40 69.9 Example 4 + + 3 a 40 57.2 Example 5 + + 1曰75 61 7 Example 6 + + 3曰75 50.5 (Test Example 2: Inhibition of IL-2 production) Investigation of inhibition of IL-2 production by inflammatory mediators The jurkat cell line uses the working stock stored in the / East knot. The stock cell line is used in the range of no more than 10 times. The medium is RPMI1640 as the base medium, and 56 乞 is added thereto. 10% fetal calf serum inactivated for 3 minutes. Culture system The carbonic acid gas culture machine was carried out at a concentration of 5% carbonic acid gas at 37 ° C under 100% humidification. In the test, the culture state of the semi-pool was used. The cells were suspended at a concentration of 2χ 1 〇 5 cells/mL. Turbidity 25 mL' was added to the concentration of ph〇rb〇l myristate acetage (PMA) of 12.5 pL and 7.5 μί of i〇pg/mL concentration (^g/mL concentration)

The Ca2+ ionophore A23187 was again suspended. The cell suspension was dispensed into a 24-well culture plate (manufactured by BDFalcon) at a concentration of 1 mL/point, and each test 101106175 26 201238593 test sample (Example 2 and Comparative Examples 2 to 3) was added thereto. After about 24 hours, the amount of IL-2 contained in the culture supernatant was measured by EUSA method (DouSet ELISA Development System human IL-2; manufactured by R&D Systems). Further, each sample was dissolved in dmSO and added to the medium at 0.2% by volume, and the final concentration was set to 5 mg/mL. The results are shown in Figure 2 and Table 3. The light irradiation treatment of the mixture of the large ugly extract and the chlorophyll was carried out, and Example 2' significantly inhibited the production of IL-2. On the other hand, in Comparative Examples 2 to 3 in which chlorophyll was not added, there was no effect on the production of IL-2 regardless of the presence or absence of photo-treatment. [table 3]

Chlorophyll light irradiation time illuminance X irradiation time (klx · hr) IL-2 production amount (%vs control group) UJ

The anti-inflammatory agent of the present invention is produced by using sauerkraut as chlorophyllogen. At the end of the reading (Western milling system) 2 〇〇g mixed vegetable powder (Japanese powder, chlorophyll content = lmg / g) 16g (soy and chlorophyll mass ratio 12500 丄). 500 ml of ethanol was added to the mixture of l〇〇g and 75. (:, 300 rpm After applying the sweat for 3 hours, the glass fiber filter paper (manufactured by Kirsaiyama Seisakusho Co., Ltd.) was used to remove the insoluble matter, and the ethanol was added to obtain a powder of 4.0 g (yield 4%). Next, 5 ha powder was used at 25 ° C. , 2klx/h irradiation, light irradiation treatment 6 101106175 27 201238593 曰, the anti-inflammatory agent of the present invention is obtained. (Example 8) The anti-inflammatory agent of the present invention is produced by using green juice as chlorophyllogen. Soya Flower (Nissin Oillio group) mixed green juice powder (produced by Nisshin Pharma; chlorophyll content = 4mg / g) 3.5g (mass ratio of soybean to chlorophyll = 1786: 1), ethanol 125mL, and 85 ° C, After stirring at 300 rpm for 3 hours, it was filtered using a glass fiber filter paper (manufactured by Kirsai Seisakusho Co., Ltd.) to remove insoluble matter, and ethanol was distilled off to obtain 1.5 g of a powder (yield 5%). Then, the powder was subjected to 25 ° C, 2 kl x / h. The anti-inflammatory agent of the present invention was obtained by irradiation with light irradiation treatment. (Comparative Examples 8 to 9) The same procedures as in Examples 7 and 8 were carried out, but Comparative Examples 8 and 9 were separately prepared under the conditions of 20. (Test Example 3: NO production inhibition effect) Using Examples 7 to 8 and The compositions of Comparative Examples 8 to 9 were used as samples, and the inhibitory activity against NO production was measured in the same manner as in Test Example 1. Further, each sample was dissolved in DMSO and added to the medium in accordance with 2% by volume, and the final concentration was carried out. The composition of Example 7 and Comparative Example 8 was 〇.〇5rng/mL, and the composition of Example 8 and Comparative Example 9 was 0.1 mg/mL. The results are shown in Fig. 3 and Table 4. Even when using spinach or green juice as In the case of chlorophyll, in the mixture obtained by combining the light irradiation treatment and the heat treatment, a remarkable NO production inhibitory activity was observed. On the other hand, in the case where the light irradiation 101106175 28 201238593 treatment and heat treatment were not treated, No NO production inhibitory activity was observed in the obtained mixture. [Table 4] Soybean seed chlorophyll light irradiation time • Heating time illuminance X irradiation time (klx · hr) Heating temperature (°C) NO production amount (% vs control Group) Example 7 Soybean powder spinach 6 a 3 hours 2x144 75 7.1 Example 8 Soybean defatted powder green juice 6 曰 3 hours 2x144 85 -2.5 Comparative Example 8 Soybean powder spinach one - 77.4 Comparative Example 9 Soy defatted powder End green juice - _ 84.7 [Simple illustration of the diagram] Figure 1 shows the inhibitory effect of NO production in megatuber cells. Figure 2 shows the inhibitory effect of IL-2 production in T cells. Figure 3 shows NO in macrophages. The suppression effect produced. 29 101106175

Claims (1)

201238593 VII. Patent Application Range: 1. The use of a mixture of soy seeds or their extracts and chlorophyll which are activated by light irradiation treatment and/or heat treatment is used for the manufacture of anti-inflammatory agents. 2. The use of the first aspect of the invention, wherein the light irradiation treatment is performed by irradiating light in such a manner that the product of the degree (kilogram: klx) and the irradiation time (hr) is 40 klx · hr or more. 3. The use according to the first aspect of the invention, wherein the heat treatment is carried out by heating at a temperature of 40 to 105 ° C for 0.5 to 144 hours. 4. The use of any one of claims 1 to 3 wherein the mixture is a mixture of soybean seed extract and chlorophyll. 5. The use of the fourth aspect of the patent application, wherein the mass ratio of the soybean seed extract to the chlorophyll in the mixture is 50,000:1 to 10:1. 6. The use of any one of clauses 1 to 3, wherein the mixture is a mixture of a soybean seed powder and a powder of a plant or an alga. 7. The use of claim 6 wherein the mass ratio of the soybean seed powder to the plant or algae powder in the mixture is 5000:1 to 1:10. A method for producing an anti-inflammatory agent, comprising: a step of obtaining a mixture of soybean seeds or an extract thereof and chlorophyll; and a step of activating the mixture by light irradiation and/or heating. 9. The method of claim 8, wherein the activation treatment by light irradiation 101106175 30 201238593 illuminates the light according to a degree (a kilogram: a product of the irradiation time (four) of 4 gents or more) The method of claim 8, wherein the heating treatment is performed by heating at a temperature of 4 G to (9) C for 0.5 to 144 hours. H. The method of any one of the above, wherein the step of obtaining a mixture, the step of sizing to a mixture of a large extract and a chlorophyll, the method of claim 11, wherein the mixture is The mass ratio of the ugly seed extract to the chlorophyll is 50,000: 1 to 10: i. The method of any one of the preceding claims, wherein the step of obtaining the mixture is to obtain soybean The method of the mixture of the seed powder and the powder of the plant or the algae. The method of claim 13, wherein the soybean seed powder in the mixture and the powder of the plant or algae The ratio is 5〇〇〇: 1~1: 10. 15_—the method for enhancing the anti-inflammatory action of soybean, comprising: a step of obtaining a mixture of soybean seeds or an extract thereof and chlorophyll; and A step of activation treatment by light irradiation and/or heating. 16. A medicine comprising a mixture of soybean seeds or an extract thereof and chlorophyll which are activated by light irradiation treatment and/or heat treatment. A cosmetic comprising a mixture of activated soybean seeds or an extract thereof and chlorophyll by photoirradiation treatment and/or heat treatment. 18. A food or drink containing light irradiation a mixture of activated soybean seeds or an extract thereof and chlorophyll treated and/or heat treated. 19. A feed comprising soybean seeds activated by light irradiation treatment and/or heat treatment or a mixture of extract and chlorophyll. 101106175 32