mTOR inhibitors

Abstract

To provide a composition having an excellent mTOR inhibitory effect and to provide compositions for anti-aging, anti-fatigue, antistress, improving metabolism, diet, moisturizing, improvement of skin firmness or gloss, cognitive decline prevention, immunosuppression, antiallergy, cancer prevention, and cancer progression inhibition.SOLUTION: Provided are a composition, which is a cosmetic, food / beverage product, pharmaceutical, or quasi-drug, comprising royal jelly and / or propolis, and Nemacystus decipiens (mozuku) or an extract thereof; an mTOR inhibitor comprising royal jelly and / or propolis, and mozuku or an extract thereof; and a composition for anti-aging, anti-fatigue, anti-stress, improving metabolism, diet, moisturizing, improvement of skin firmness or gloss, cognitive decline prevention, immunosuppression, anti-allergy, cancer prevention, and cancer progression inhibition, comprising royal jelly and / or propolis, and mozuku or an extract thereof.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition having an mTOR inhibitory effect. For anti-aging, anti-fatigue, anti-stress, metabolism improvement, dieting, moisturizing, skin elasticity Or for improving skin tone, preventing cognitive decline, suppressing the immune system, anti-allergy, and preventing cancer, Or it relates to a composition for inhibiting the progression of cancer. [Background technology]

[0002] Mechanistic (mammalian) target of rapamycin (mTOR) is a neurotransmitter that regulates the function of the rapamycin receptor in mammals and other animals. It is a type of protein kinase involved in intracellular signal transduction, protein translation, autophagy, and It plays important roles in phagy, immune regulation, cytoskeleton regulation, gene transcription, etc., and is involved in cell growth, division, and mTOR is deeply involved in fundamental life phenomena such as cancer and death. This protein has a molecular weight of 29 and is found to be the intracellular target of rapamycin, which has anticancer properties. It was revealed that the kinase is a large serine-threonine kinase with a molecular weight of 10,000.

[0003] Two types of mTORC1 complexes composed of multiple proteins that differ in their interactions with rapamycin mTORC1 and mTORC2 are involved in multiple biological reactions. In particular, mTORC1 regulates the synthesis of ribosomes and proteins. mTOR plays an important role in maintaining life, including the synthesis of nucleic acids and lipids. Rapamycin, which primarily regulates C1, is known to mediate lifespan extension in many organisms, from nematodes to rodents. The effects of prolonging lifespan have been scientifically confirmed, and clinical trials for lifespan extension are being conducted in primates, including humans. In addition, autophagy, which recycles intracellular organelles, has been promoted. Browning of fat cells that promotes metabolism, suppression of cognitive decline by reducing the deposition of beta-amyloid, and inflammation. It has various functions, such as immunosuppression by suppressing the secretion of pathogenic cytokines and the proliferation of various types of cancer cells. It has the potential to be used in the treatment of cancer (Non-Patent Documents 1 and 2).

[0004] Recently, inhibition of mTORC1 has been shown to increase the expression of cathepsin H, which is a hydrating regulator. It was found that mTOR inhibits phosphorus production, which suggests that it may be effective in preventing skin aging. It is expected to have effects such as moisturizing and moisturizing (Non-Patent Document 3).

[0005] Mozuku (seaweed) is a type of seaweed found along the coasts of Japan, especially in inner bays, and is eaten raw. In Japan, it is mainly eaten as a vinegared dish. It is known that it contains a lot of polysaccharides such as alginic acid and fucoidan as useful ingredients. It is being done.

[0006] Regarding the effects of fucoidan, Patent Document 1 states that fucoidan derived from mozuku seaweed has anti- It has been reported that it enhances the effects of cancer drugs and inhibits the effects of anti-cancer drugs on normal stomach cells. It has been done.

[0007] Propolis is made from tree sap, plant buds and exudates collected by honeybees. It is a glue-like substance made by mixing with beeswax, etc., and has antibacterial, antioxidant, and anti-inflammatory properties. It is known to have antitumor and antiallergic effects.

[0008] Regarding such effects of propolis, Patent Document 2 describes a micellar extract of propolis. However, it improves or prevents the decline in cognitive function associated with NMDA (N-methyl-D-aspartate) receptors. It has been reported that it is useful as a medicine and food and beverage. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] JP 2004-75595 A [Patent Document 2] JP 2018-24654 A [Non-patent literature]

[0010] [Non-Patent Document 1] Cold Spring Harb Perspect Med. 2016 6(5): Pii 1-19 [Non-Patent Document 2] Cell Metabolism 23, 2016, 990-1003 [Non-Patent Document 3] J Allergy Clin Immunol. 2017 Apr; 139(4): 1228-1241 Summary of the Invention [Problem to be solved by the invention]

[0011] An object of the present invention is to provide a composition having an excellent mTOR inhibitory effect. The present invention relates to an mTOR inhibitor and a compound for use in anti-aging, anti-fatigue, anti-stress, improving metabolism, and dieting. For skin care, moisturizing, improving skin firmness or luster, preventing cognitive decline, immunosuppression, anti-aging The present invention aims to provide a composition for allergies, cancer prevention, or cancer progression inhibition. [Means for solving the problem]

[0012] As a result of intensive research aimed at achieving the above object, the present inventors have discovered that an extract of Mozuku seaweed is When added to jelly or propolis, the activity of each component is less than the sum of their activities (arithmetic mean). This means that at least 1.7 times stronger mTOR inhibitory activity can be achieved, i.e., a synergistic effect can be achieved. I gained some insight.

[0013] Based on these findings, and through further investigation, the present invention has been completed, and provides the following composition: The Company provides products such as mTOR inhibitors.

[0014] Item 1. Cosmetics, food and beverages, medicines, or quasi-drugs. A composition comprising royal jelly and / or propolis, and mozuku seaweed or an extract thereof. Item 2. mTOR inhibitors containing royal jelly and / or propolis, and mozuku or its extract Harmful agent. Item 3. Anti-aging products containing royal jelly and / or propolis, and mozuku seaweed or its extract For skin care, anti-fatigue, anti-stress, metabolism improvement, dieting, moisturizing, skin elasticity For improving lustre, preventing cognitive decline, suppressing the immune system, anti-allergy, preventing cancer, or A composition for inhibiting the progression of cancer. Item 4. The composition according to item 3, which is a cosmetic, a food or drink, a pharmaceutical, or a quasi-drug. Effect of the Invention

[0015] The composition of the present invention has a synergistic effect of royal jelly or propolis and mozuku or an extract thereof. As a result, it has excellent mTOR inhibitory activity. The combination of mozuku or its extracts is effective as an mTOR inhibitor and for anti-aging, anti-fatigue, and anti-stress. For weight loss, for improving metabolism, for dieting, for moisturizing, for improving skin firmness or luster, for cognitive function Composition for preventing hypoxia, suppressing immunity, anti-allergy, preventing cancer, or inhibiting the progression of cancer It is useful as a part.

[0016] In addition, royal jelly, propolis, and mozuku are all natural ingredients and therefore safe. Highly sexual. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Hereinafter, an embodiment of the present invention will be described in detail.

[0018] In this specification, "comprise" means "essentially consisting of" It also includes the meaning of "essentially consist of" and the meaning of "consist of only." Includes.

[0019] The compositions and mTOR inhibitors of the present invention are prepared by combining royal jelly and / or propolis, as well as shrike. The present invention is characterized in that it contains ginger or an extract thereof.

[0020] (Royal Jelly) Royal jelly is a substance secreted by honeybee worker bees that are 3 to 12 days old from the hypopharyngeal and mandibular glands. Royal jelly is a milky white jelly-like substance made by mixing secretions from the bloodstream. As an ingredient, for example, 10-hydroxy-2-decenoic acid, which is specific to royal jelly (hereinafter referred to as " In addition to organic acids such as decenoic acid, proteins, lipids, sugars, B vitamins, Examples of the vitamins include folic acid, nicotinic acid, pantothenic acid, and various minerals. In the Ming Dynasty, royal jelly was classified into fresh royal jelly, dried royal jelly, and dried royal jelly. Jelly powder, enzyme-treated royal jelly, royal jelly extract, royal jelly fermentation product, etc. Royal jelly is produced in European countries, Oceanian countries, and the United States. The country may be any of the following: South Africa, Brazil, Japan, China, or other Asian countries.

[0021] Dried royal jelly powder is made by drying and powdering fresh royal jelly.

[0022] Enzyme-treated royal jelly is made by treating royal jelly with a protein-degrading enzyme (protease). Preferably, the tallow contained in royal jelly is treated with a protease. Hypoallergenic enzyme-treated royal jasmine, which suppresses allergic reactions caused by protein Therefore, the enzyme-treated royal jelly contains In addition to the protease decomposition products of proteins, organic acids such as the aforementioned decenoic acid, lipids, sugars, Vitamins and various minerals may be included.

[0023] The royal jelly used in the production of the enzyme-treated royal jelly is not particularly limited. For example, raw royal jelly, dried and powdered raw royal jelly, Examples include powder, or raw royal jelly extracted with water or aqueous ethanol. can be.

[0024] The production of enzyme-treated royal jelly involves the conversion of royal jelly raw material into at least endopeptides. Enzymes with enzymatic activity, enzymes with at least exopeptidase activity, and / or enzymes with This is carried out by treating the product with an enzyme having dopeptidase and exopeptidase activity. It is possible.

[0025] As proteolytic enzymes having at least endopeptidase activity, animal-derived ( trypsin, chymotrypsin, etc.), plant-derived (e.g. papain, etc.), microbial-derived (For example, endopeptidases from lactic acid bacteria, yeast, mold, Bacillus subtilis, actinomycetes, etc.) do.

[0026] As a proteolytic enzyme having at least exopeptidase activity, carboxylase Peptidases, aminopeptidases, derived from microorganisms (e.g., Lactobacillus, Aspergillus spp.) and Rhizopus sp.) Examples of such supplements include creatine and pepsin.

[0027] Among these various enzymes, those with both exopeptidase and endopeptidase activities A preferred example of the enzyme is Streptomyces griseus. eus produced peptidase (trade name: Actinase AS), Aspergillus oryzae (Aspergill oryzae)-produced peptidase (product name: Protease A, Flavorzyme, Proteac Aspergillus melleus-produced peptidase (product name: Propionyltransferase) A preferred example of an enzyme having exoprotease activity is aspartate. Aspergillus oryzae produced peptidase (trade name: Umamizyme G, Pr omod 192P, Promod 194P, Sumiteam FLAP), Aspergillus sojae e) peptidase produced by Aspergillus sp. (trade name: Sternzyme B15024), peptidase produced by Aspergillus sp. ( Product name: Coclase P), Rhizopus oryzae-produced peptidase (product name Furthermore, preferred examples of the enzymes having endoprotease activity include peptidase R. A preferred example is the peptidase produced by Bacillus subtilis (trade name : Orientase 22BF, Nucleisin, Bacillus licheniformis niformis)-produced peptidase (trade name: Alcalase), Bacillus stearothermophila Peptidase produced by Bacillus stearothermophilus (product name: Protease S), Peptidase produced by Bacillus amyloliquefaciens (product name: Ni Examples of the enzymes that can be used include the peptidase produced by Bacillus sp. (trade name: Protamex) and the peptidase produced by Bacillus sp. can.

[0028] Enzyme treatment to reduce the allergenicity of royal jelly is described, for example, in JP 2007-29591 A. This can be carried out according to the description in Japanese Patent Application Laid-Open No. 2007-295920.

[0029] Royal jelly extract is made by dissolving royal jelly (including raw, dried and crushed royal jelly) in water or water-containing It is extracted with ethanol, etc.

[0030] Royal jelly fermentation is produced by conventional methods using microorganisms such as yeast and lactic acid bacteria. can be done.

[0031] (Propolis) Propolis is a resinous or waxy substance that constitutes the walls of honeybee hives. Propolis is widely used in, for example, Brazil, China, European countries, Oceania, and the United States. The origin of the plant may be any, such as mosquitoes, etc. Any type of propolis can be used, including supergreen, eucalyptus, and ultragreen.

[0032] The propolis in the present invention may include, for example, raw propolis or residue, its pulverized product, supercritical Extracts of the microbial organism, extracts of the microbial organism using water or a hydrophilic organic solvent, powders of the extracts, Among them, the hydrophilic organic solvent extract contains the active ingredient of propolis. The extracts are extracted efficiently and in a balanced manner in a short time. This is preferable because it does not require large-scale equipment.

[0033] As the hydrophilic organic solvent extraction solution, lower alcohols such as ethanol, methanol, and propanol are used. The propolis extract is preferably extracted from raw propolis mass or residue, Alcohol-washed raw propolis or residues can be used, and cut into appropriate sizes. The extraction efficiency can be improved by using cut or crushed propolis raw material or residue. can.

[0034] (Mozuku seaweed or its extract) The mozuku used in the present invention is a member of the Chordariaceae family of the Phaeophyceae order, or It is an algae belonging to the family Spermatochnaceae of the order Chondrus. There are no particular limitations on the type of mozuku seaweed as long as it is edible, and it is preferably from the family Chondrus. The species includes Sphaerotrichia firma, Sphaerotrichia di varicata), Okinawan mozuku (Cladosiphon okamuranus), Futomozuku (Tinocladia crassa) and Nemacystus decipiens, which belongs to the family Mozuku. Preferably, it is Ishimozuku or Mozuku. In the present invention, wild mozuku and cultivated mozuku are also preferred. In the present invention, either fresh mozuku immediately after harvesting or refrigerated mozuku can be used. Any of the following can be used: frozen mozuku, salted mozuku, salted and frozen mozuku, dried mozuku, etc. can.

[0035] There are no particular limitations on the part of the mozuku seaweed that can be used, and any part can be used. In addition, mozuku is used as a raw material in its original form without being cut or crushed. Alternatively, sliced ​​or crushed pieces may be used.

[0036] In the present invention, an extract of Mozuku can be used, and the extract can be obtained by any method. The method for obtaining the extract of Mozuku is not particularly limited. , a method of extracting using a polar solvent, a method of extracting using supercritical fluid such as carbon dioxide, etc. Examples include the law.

[0037] When extracting with a polar solvent, the extraction solvent used may be, for example, water, lower alcohol ( Methanol, ethanol, n-propanol, isopropanol, etc.), ketones (acetonitrile, ketone, methyl ethyl ketone, methyl butyl ketone, etc.), esters (methyl acetate, ethyl acetate, etc.), glycols (ethylene glycol, propylene glycol, etc.), glycerin , Tetrahydrofuran, Acetonitrile, Acetic acid, Propionic acid, Acetamide, Dimethyl Examples include formamide and dimethyl sulfoxide.

[0038] These extraction solvents can be used alone or in any combination of two or more to form a mixture. Preferably, water, a lower alcohol (preferably ethanol) or the like is used. The mixture of these (water-containing alcohol, preferably water-containing ethanol) is used as the extraction solvent. When alcohol (preferably hydrous ethanol) is used, the alcohol concentration is not limited. Although it is not possible to obtain a total volume of the mixture, a volume of 20 to 90% by volume, and particularly 40 to 80% by volume, can be preferably mentioned.

[0039] The mozuku used for the extraction is not particularly limited, and examples thereof include raw mozuku, dried raw mozuku, and the like. Examples include dried and powdered mozuku seaweed.

[0040] Extraction is carried out by adding some or all of the mozuku seaweed to a solvent and heating it at a temperature between 0℃ and the boiling point of the solvent, usually above 100℃. Leave the mixture at room temperature for 30 minutes to 3 days or extract it by soaking and shaking at the temperature below, then remove the insoluble matter. The hot water extraction can be easily carried out by, for example, heating the mixture in hot water at 60 to 100°C, preferably at 80°C. Extraction is performed by soaking and leaving to stand or soaking and shaking in hot water at 0 to 90°C for 30 minutes to 3 hours. The solvent extract thus obtained can be used as it is, or can be used as necessary. , ultrafiltration, molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange Exchange chromatography, affinity chromatography, high performance liquid chromatography Further purification may be carried out by high performance liquid chromatography (HPLC), dialysis, a combination thereof, etc. The solvent extract may also be Concentration and drying treatment such as freeze drying and spray drying may also be performed. The shrinkage, freeze-drying and spray-drying can be carried out according to conventional methods.

[0041] The content of fucoidan in the mozuku extract used in the present invention is, for example, 90% or less. Mass % or less, 80 mass % or less, 70 mass % or less, 60 mass % or less, 50 mass % or less, 40 mass % or less, 30 quality % by mass or less, 20% by mass or less, 10% by mass or less, or 5% by mass or less, or fucoidan Fucoidan does not have mTOR inhibitory activity.

[0042] The ratio of mozuku or its extract contained in the composition and mTOR inhibitor of the present invention is There are no particular limitations as long as the effect can be obtained, and the amount can be adjusted appropriately depending on the final form, etc. The content can be appropriately selected from the range of preferably 1 to 80% by mass, more preferably 2 to 50% by mass. It is Noh.

[0043] In the composition and mTOR inhibitor of the present invention, the amount of loxonitrile is 1 part by mass of mozuku or its extract. Yarjelly is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 70 parts by mass, and even more preferably The content is preferably 0.1 to 50 parts by mass, and particularly preferably 1 to 30 parts by mass.

[0044] In the composition and mTOR inhibitor of the present invention, the amount of protease inhibitor is 1 part by mass of mozuku or its extract. The amount of the polysulfone is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 70 parts by mass, and further preferably is 0.1 to 50 parts by mass, more preferably 1 to 30 parts by mass, and particularly preferably an amount exceeding 1 part by mass The content is preferably from 2.2 to 20 parts by mass, and most preferably from 2.2 to 20 parts by mass.

[0045] The composition and mTOR inhibitor of the present invention may contain any other publicly known substances than those mentioned above, as long as they do not impair the effects of the present invention. The ingredients of knowledge can be mixed appropriately.

[0046] The composition and mTOR inhibitor of the present invention can be used in cosmetics, foods and beverages (particularly for health, health maintenance, improvement, etc.) The desired food and drink (e.g., health food, functional food, nutritional composition) n) Nutritional supplements, supplements, health foods, foods for specified health uses, functional foods, or functional foods The present invention can be used as a food with functional labeling, a quasi-drug, a medicine, etc. The composition and mTOR inhibitor have mTOR inhibitory effects, anti-aging effects, anti-fatigue effects, anti-stress effects, and metabolic effects. Improves metabolism, diet, moisturizes, improves skin elasticity and luster, and reduces cognitive impairment It has anti-inflammatory, immunosuppressive, anti-allergic, cancer prevention, and cancer progression suppression effects. The meaning of the additives to be added is also included.

[0047] The above cosmetics contain, in addition to the royal jelly, propolis, and mozuku seaweed or their extracts, , ingredients commonly used in cosmetics, such as whitening agents, moisturizing agents, antioxidants, oily ingredients, ultraviolet Radiation absorbers, surfactants, thickeners, alcohols, powder ingredients, coloring materials, water-based ingredients, water, various skins Skin nutrients and the like can be appropriately blended as needed.

[0048] Cosmetics include the skin, mucous membranes, body hair, head hair, scalp, nails, teeth, facial skin, and lips of animals (including humans). This includes any cosmetic product that is applied to the skin, etc.

[0049] Cosmetics are available in a variety of formulations, including aqueous solutions, solubilized solutions, emulsions, powders, oils, gels, ointments, and emulsions. A wide range of formulations are available, including azole systems, water-oil two-layer systems, and water-oil-powder three-layer systems.

[0050] The use of cosmetics is also arbitrary. For example, basic cosmetics can be face wash, lotion, milky lotion, cream, etc. Creams, gels, essences, serums, packs, masks, etc. are included in the makeup Products include foundation, lipstick, blusher, eyeshadow, eyeliner, mascara, etc. For nail cosmetics, nail polish, base coat, top coat, nail polish remover, etc. Other uses include face washes, toothpastes (paste or liquid), mouthwashes, and massage creams. Cleansing agent, aftershave lotion, preshave lotion, shaving lotion Bathing cream, body soap, soap, shampoo, conditioner, hair treatment, Examples include hair styling products, hair tonics, hair growth products, antiperspirants, bath additives, etc.

[0051] The above-mentioned food and drink contains the above-mentioned royal jelly, propolis, and mozuku seaweed or their extracts. It can be used as is, or as needed, it can be supplemented with minerals, vitamins, flavonoids, and vitamin C. Non-foods, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants Disintegrants, lubricants, colorants, flavorings, stabilizers, preservatives, sustained-release regulators, surfactants, dissolving agents, humectants, A lubricant and the like can also be added.

[0052] Food and beverages include any food or beverage that can be consumed by animals (including humans). Types of food and beverages are not particularly limited, and examples thereof include dairy products; fermented foods (yogurt, royal jelly, etc.); beverages Types (soft drinks such as coffee, juice, and tea drinks, dairy drinks, lactic acid bacteria drinks, and drinks containing lactic acid bacteria) drinks, yogurt drinks, carbonated drinks, sake, Western liquor, fruit wine, etc.); spreads (cafes, etc.) Stirred cream, etc.); Pastes (fruit paste, etc.); Western confectioneries (chocolate, dough, etc.) Nuts, pies, cream puffs, gum, jellies, candies, cookies, cakes, puddings, etc. ); Japanese sweets (daifuku, mochi, manju, castella, anmitsu, yokan, etc.); frozen desserts (ice cream, Popsicles, sherbet, etc.); food (curry, beef bowl, porridge, miso soup, soup, sauces, pasta, pickles, jams, etc.); condiments (dressings, furikake, umami seasonings) , soup bases, etc.

[0053] The method for producing the food and drink of the present invention is not particularly limited, and can be any known method as appropriate.

[0054] There are no particular limitations on the dosage unit form when used as a supplement and it can be selected appropriately. For example, tablets, capsules, granules, liquids, powders, etc. are included.

[0055] The intake amount of the food or drink of the present invention may vary depending on various conditions of the person taking it, such as the weight, age, sex, and symptoms. The above can be set appropriately.

[0056] The above medicines contain only the above royal jelly, propolis and mozuku seaweed or their extracts. It can also be used in combination with other medicinal ingredients listed in the Japanese Pharmacopoeia, such as vitamins and herbal medicines. It can also be used.

[0057] When the composition and mTOR inhibitor of the present invention are prepared as a pharmaceutical product, the above royal jelly, Propolis and mozuku or their extracts are mixed with non-toxic carriers and diluents that are acceptable for pharmaceutical use. Tablets (plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, etc.) are prepared with a drug or excipient. (including chewable tablets, lozenges, etc.), capsules, pills, powders, fine granules, granules The drug may be administered orally (e.g., orally) in the form of a liquid, suspension, emulsion, syrup, paste, etc. It is possible to prepare pharmaceutical formulations (for use in medicine).

[0058] The dosage of the drug is determined appropriately according to various conditions such as the patient's weight, age, sex, and symptoms. It is possible.

[0059] The pharmaceuticals and cosmetics of the present invention also include quasi-drugs.

[0060] The composition and mTOR inhibitor of the present invention described above can be administered to mammals, including humans (preferably humans). This applies to:

[0061] The composition and mTOR inhibitor of the present invention are a combination of royal jelly or propolis and mozuku seaweed or its extract. It has excellent mTOR inhibitory effects due to its synergistic effect with other products.

[0062] As a result of mTOR inhibition, lifespan extension, autophagy enhancement, browning of white adipocytes, It has been reported that it has moisturizing effects on the skin, improves cognitive function, suppresses the immune system, and has anticancer effects. It has been reported that the effects of enhancing autophagy include anti-fatigue and anti-stress effects. However, the effects of browning white fat cells include improving metabolism and dieting. The moisturizing effect includes improving the moisture, firmness and luster of the skin.

[0063] Therefore, the combination of royal jelly or propolis with mozuku or its extract is mTOR inhibitors, and anti-aging, anti-fatigue, anti-stress, metabolic improvement, dieting, moisturizing For improving skin elasticity or luster, for preventing cognitive decline, for immunosuppression, for anti-allergy It is useful as a component of a composition for preventing cancer or inhibiting the progression of cancer.

[0064] Types of cancer include stomach cancer, colon cancer (rectal cancer, colon cancer), small intestine cancer, liver cancer, pancreatic cancer, and lung cancer. , pharyngeal cancer, esophageal cancer, kidney cancer, gallbladder and bile duct cancer, head and neck cancer, bladder cancer, prostate cancer, breast cancer, uterus These include cancer (cervical cancer, uterine cancer), ovarian cancer, brain tumors, leukemia, malignant lymphoma, multiple myeloma, etc. Can be obtained.

[0065] In addition, the composition and mTOR inhibitor of the present invention are safe because they contain naturally derived active ingredients. is high. EXAMPLES

[0066] The present invention will be described in detail below with reference to examples. However, the present invention is not limited to these examples. The present invention is not limited to the above.

[0067] Test Example <Material> Raw royal jelly (untreated), enzyme-treated royal jelly and propolis ethanol extract The freeze-dried powder of the extract was dissolved in DMSO and used for the test. According to the method described in Example 1 of the 120th Publication, the powder of the ethanol extract of propolis is alexrin. The ethanol extract of raw propolis (produced in Minas Gerais, Brazil) was freeze-dried and crushed. I gained this by doing this.

[0068] The mozuku used is Iwamozuku from Oki Island (collected from the sea of ​​Oki Island) and Sado Island mozuku (collected from the sea of ​​Niigata Prefecture). (purchased from the Bandaijima Fresh Fish Center, Central Fisheries Market Co., Ltd.) was used. The mozuku seaweed was washed and cut into pieces. The freeze-dried material was then crushed into small pieces in a mill, and 10 ml of the powder was added to 1 g of mozuku seaweed. Milli-Q (registered trademark) water was added, and the mixture was immersed in a water bath kept at 90°C for 1 hour. The mixture was centrifuged at 6,000 rpm and 25°C for 15 minutes, the supernatant was filtered, and the water was removed using an evaporator. A small amount of water was added, the mixture was frozen at -20°C, and then freeze-dried to obtain a powdered extract of Mozuku seaweed.

[0069] <Reagents> mTOR: eurofins #14-770 -ULight TM -4E-BP1 (Thr37 / 46) Peptide:PerkinElmer #TRF0128-D, #TRF0128-M ·Europium-anti-phospho-4E-BP1 (Thr37 / 46) Antibody:PerkinElmer #TRF0216-D, #TRF 0216-M ·PI-103:Cayman Chemical (CAS 371935-74-9) ·10X LANCE Detection Buffer:PerkinElmer #CR97-100 ·Kinase buffer (KB):50mM HEPES(pH 7.5), 1mM EGTA, 3mM MnCl2, 10mM MgCl2, 0 0.01% Tween-20, 2 mM DTT

[0070] <Experimental Method> Ethanol of raw royal jelly (raw RJ), enzyme-treated royal jelly (RJ), and propolis (PP) The extract and the powdered extract of Mozuku were dissolved in DMSO, and then the materials alone, raw RJ, RJ or PP and Mozuku were The mTOR inhibitory activity of an equal mixture of these drugs was evaluated. The inhibitory activity was evaluated by the TR-FRET method.

[0071] [Test procedure] KB: mTOR 40 nM, ATP 5 mM, PI-103 (Inhibitor) 40μM, ULight TM -4E-BP1 (Th r37 / 46) Peptide 200 nM was prepared. Europium-ant peptide was detected using 10X LANCE Detection Buffer. i-phospho-4E-BP1 (Thr37 / 46) Antibody 80μM (4X Detection buffer) was prepared. PI-1 03 40μM was diluted 5-fold, 8 times, and used as a positive control (DMSO concentration was kept constant at 4%). Royal jelly, propolis, and mozuku were each taken at 3, 0.6, 0.12, and 0.024 μg / mL) and royal jelly / propolis (30, 6, 1.2, 0.24μg / mL) were dissolved in DMSO. The mixture was used as a test sample. Used as a pool.

[0072] In a MicroPlate (Greiner #784075), 2.5 μL of mTOR, 1.25 μL of inhibitor or test sample, and U Add 1.25μL of Light-4E-BP1 (Thr37 / 46) Peptide / ATP mix (ATP 80μM) and attach a Plate Seal. The plate was left to stand at room temperature for 1 hour. 2.5 μL of Stop Solution (32 mM EDTA in 1X Detection Buffer) and allowed to stand at room temperature for 5 minutes.

[0073] 2.5μL Detection Mix (Eu-anti-phospho-4E-BP1 (Thr37 / 46) Antibody final concentration 2 nM) The plate was sealed and left to stand at room temperature for 1 hour. TM TR-FRET with Multilabel Reader Measurements were performed using the same excitation mode (excitation at 320 nm & emission at 665 nm).

[0074] <Result> The results of using Iwamozuku from Okinoshima and Mozuku from Sado Island are shown in Tables 1 and 2 below.

[0075] [Table 1]

[0076] [Table 2]

[0077] Raw and enzyme-treated royal jelly inhibited mTOR regardless of the concentration in the range of 0.24 to 30 μg / mL. No toxicity was observed. The 50% inhibitory concentration (IC 50 ) was 23.24μg / mL. ZUKI single IC 50 The Iwamozuku from Oki Island had 4.266μg / mL, while the Sado Island mozuku had 1178μg / mL. When RJ or PP was mixed with mozuku, the results showed that the Iwamozuku from Oki Island In this case, IC of Mozuku + RJ 50 = 2.44 μg / mL, IC of Mozuku + PP 50 = 1.812μg / mL, which is an additive effect. The inhibitory activity was 1.7 and 1.9 times stronger than the theoretical value when it was assumed that the In the case of Mozuku, IC of Mozuku + PP 50 = 2.568μg / mL, the theoretical value assuming additive effects. The inhibitory activity was 6.7 times stronger than the original value.

Claims

[Claim 1] 1. An mTOR inhibitor comprising royal jelly and / or propolis, and mozuku or an extract thereof, wherein the mozuku is Sphaerotrichia firma belonging to the family Chosanthellaceae of the order Chosanthellaceae.

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