JP2012072132A - Life-extending agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medicine and a food and drink which have no side effect, have high safety, can be taken easily, show a life-extending effect, particularly a healthy life-extending effect, and show an in vivo antioxidant function-improving effect.SOLUTION: The agent can extend lives of organisms such as human, dog, cat, and nematode, can preferably extend a healthy life, and can improve the in vivo antioxidant function by the intake of astaxanthin as an active ingredient. The user can take astaxanthin as a form of medicine which contains astaxanthin in an amount of 0.0001-10 mg per day.

Description

  The present invention relates to a life extending agent and a biological antioxidant function improving agent.

  Japan is one of the longest-lived countries in the world with a life expectancy of 79.6 years for men and 86.4 years for women in 2009. However, although Japan has become a longevity country, so-called lifestyle-related diseases have been increasing due to the westernization of eating habits, decreased exercise, and increased social stress. Therefore, even though the average life expectancy has been prolonged, aging such as decreased memory ability, decreased physical function such as decreased gait, and increased number of elderly people who are bedridden due to brain, nerve or circulatory disorder, etc. Declining of life (QOL) and socially increasing nursing care and medical expenses are problems.

  In order to remedy these problems, the Health Promotion Act has been enacted, and national health promotion measures in the 21st century have been actively implemented. In addition, people's interest in food has increased and research on functional ingredients of food has been actively promoted. If you can maintain your health by improving your diet and lifestyle, it will lead to the improvement and prevention of diseases such as metabolic syndrome caused by lifestyle, which is a problem today. .

  Astaxanthin is widely distributed in nature, especially in the ocean, such as crustaceans such as shrimp and crab, fish such as salmon and Thailand, algae such as green alga Hematococcus, yeast such as red yeast faffia, etc., and is used as a red pigment It has been found to have an antioxidant action about 1000 times that of vitamin E and about 40 times that of β-carotene (Patent Document 1). In addition, the effects of photoaging and skin aging prevention by applying astaxanthin to the skin are known (Patent Documents 2 and 3). In recent years, the use of astaxanthin as a supplement has been increasing.

  However, astaxanthin acts on various living functions in the living body, and it is not known about the effect of extending the life of an individual organism, particularly the effect of extending the healthy life, and the effect of improving the antioxidant function in the living body.

JP-A-2-49091 JP 2002-128651 A JP 2002-1265313 A

  Disclosed are pharmaceuticals, foods and drinks that exhibit a long life-spanning effect, particularly a healthy long-lived life-spanning effect, and an in vivo antioxidant function-improving effect that have no side effects and are easy to ingest.

  As a result of diligent studies to achieve the above-mentioned object, the present inventors have found that astaxanthin has a life-spanning action, particularly a healthy life-spanning action, as well as an The present invention was completed by finding out that it has the effect of improving the oxidation function.

  Administration and ingestion in the form of a medicinal product and food and drink containing the medicinal product as an astaxanthin active ingredient can prolong the life span, in particular, the healthy life span, and the anti-oxidant function improving action in the living body.

It is the graph which showed typically the life extension effect of the present invention. C. The survival days and survival rate by the astaxanthin dosage of an elegance (C. elegans) wild strain are shown. C. The survival days and survival rate by the astaxanthin dosage of Elegance AGE-1 stock | strain are shown.

  The present invention is a food / beverage product comprising an organism life extension agent comprising astaxanthin, an in vivo antioxidant function improving agent, and a pharmaceutical product thereof. In order to enhance these effects, a substance having an auxiliary effect described later can be added.

  The life extension agent of the present invention can prolong the life of an organism, that is, increase the period from birth to individual death. The increase effect is 1 to 2 times, preferably 1 to 1.5 times, and more preferably 1 to 1.2 times the average life of the organism. Smaller organisms with fewer cells are more effective in extending life than those with larger cells. Living creatures that have a short life span have a greater effect of extending the life span. For example, a nematode composed of about 1000 cells has a longer life extension factor than a mammal or the like. In the present invention, the organism having a life extension effect is a multicellular organism.

  Furthermore, the life extending agent of the present invention has a specific effect on extending healthy life. The healthy life expectancy is the life expectancy including the cause of internal death such as diseases caused by one's own cause, excluding accidental death of organisms, death of diseases caused by other organisms such as bacterial infection and virus infection, etc. And preventing early debilitation of a specific period among organs related to living organisms. Although the individual death draws a normal distribution centering on the average life span, the number of individual deaths is brought close to the maximum life span of each organism by the effect of the present invention. FIG. 1 schematically shows the effect of extending the healthy life of the present invention. It is possible to more effectively extend the life span of 70 to 90 years, centering on the average life span of about 80 years old for Japanese. Healthy life expectancy also includes the meaning of extending the life expectancy of social life.

  The maximum life span is set for each species, and it is difficult to survive beyond this. For example, the maximum lifespan of humans is estimated to be 120 years. Although the details of the life extension effect of the present invention are not clear, in the examples of the present invention, the nematode C. Astaxanthin has a life-span extension effect in both wild and low-energy strains of elegance, so astaxanthin is an antioxidant function in the body, an insulin / insulin-like growth factor signaling pathway, a pathway that regulates mitochondrial function, diet It is presumed to act on any one or more of the pathways that regulate the effects of restriction.

  Astaxanthin improves the antioxidant function of the living body. The antioxidation function of a living body is to improve the function of generating an enzyme that eliminates reactive oxygen species generated in the living body such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase. An increase in these enzyme activities can be confirmed by measuring the expression of related genes. So far, natural antioxidants are known to reduce the activity of reactive oxygen scavenging enzymes in order to eliminate reactive oxygen species in the living body, but the present invention has the opposite effect. Improvement of the antioxidant function in the present invention includes improvement.

  In addition, since the life extension agent of the present invention extends the healthy life expectancy, it is possible to maintain the inner state of the living organism for a longer period of time.

The astaxanthin according to the present invention will be described.
In the description of the present invention, astaxanthin includes astaxanthin and / or its ester unless otherwise specified. Furthermore, the ester of astaxanthin includes a monoester form and / or a diester form.

  As the astaxanthin of the present invention, at least one of astaxanthin free form, monoester form and diester form can be used. Diesters are chemically and physically more stable than free and monoesters because two hydroxyl groups are protected by ester bonds, and are less susceptible to oxidative degradation. However, it is considered that when it is taken into the intestine by an enzyme or into a living body, it is rapidly hydrolyzed to astaxanthin by the in vivo enzyme and exhibits an effect.

  Examples of astaxanthin monoesters include esters esterified with lower or higher saturated fatty acids or lower or higher unsaturated fatty acids. Specific examples of the lower or higher saturated fatty acid or the lower or higher unsaturated fatty acid include acetic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitooleic acid, hebutadecanoic acid, elaidic acid, ricinoleic acid, and betrothelin. Acid, vaccenic acid, eleostearic acid, punicic acid, ricinic acid, parinaric acid, gadoric acid, 5-eicosenoic acid, 5-docosenoic acid, cetoleic acid, erucic acid, 5,13-docosadienoic acid, ceracholic acid, decenoic acid , Steric acid, dodecenoic acid, oleic acid, stearic acid, eicosapentaenoic acid, docosahexaenoic acid, linoleic acid, linolenic acid, arachidonic acid and the like. Examples of carotenoid diesters include diesters esterified with the same or different fatty acids selected from the group consisting of the above fatty acids.

  Furthermore, astaxanthin monoesters include amino acids such as glycine and alanine; mono- or polyvalent carboxylic acids such as acetic acid and citric acid; inorganic acids such as phosphoric acid and sulfuric acid; sugars such as glucoside; glycerosugar fatty acids and sphingosaccharides. Examples thereof include sugar esters such as fatty acids; fatty acids such as glycero fatty acids; monoesters esterified with glycerophosphoric acid and the like. In addition, the salt of the said monoester is also included when it can be considered. Examples of fatty acid derivatives include phospholipid type, alcohol type, ether type, sucrose ester type and polyglycerin ester type of the above fatty acids.

  Astaxanthin diester, the group consisting of the lower saturated fatty acid, higher saturated fatty acid, lower unsaturated fatty acid, higher unsaturated fatty acid, amino acid, mono- or polyvalent carboxylic acid, inorganic acid, sugar, sugar fatty acid, fatty acid and glycerophosphoric acid And diesters esterified with the same or different acids selected from In addition, the salt of the said diester is also included when it can be considered. Examples of the diester of glycerophosphoric acid include saturated fatty acid esters of glycerophosphoric acid, or glycerophosphoric acid esters containing fatty acids selected from higher unsaturated fatty acids, unsaturated fatty acids or saturated fatty acids.

  Astaxanthin means a product derived from a natural product or obtained by synthesis. Examples of those derived from natural products include microalgae such as the green alga Hematococcus, yeasts such as the red yeast Phaffia, crustacean shells such as shrimp, krill and crabs, craniopod viscera such as squid and octopus, various Adonis genus petals such as seafood skins and fins of the seafood, Parasococcus sp. N81106, Brevundimonas sp. SD212, Erythrobacter sp. PC6 and other G-radians, Gordonia sp. KANMONKAZ-1129 Examples thereof include those obtained from fungi, Labyrinthulas such as Schizophytriuym sp. KH105 (especially Yabetaceae) and astaxanthin-producing genetically modified organisms. Natural extracts and chemically synthesized products are commercially available and are readily available.

  Astaxanthin is 3,3′-dihydroxy-β, β-carotene-4, 4′-dione and has stereoisomers. Specifically, three stereoisomers of (3R, 3′R) -astaxanthin, (3R, 3 ′S) -astaxanthin and (3S, 3 ′S) -astaxanthin are known. Any of these can be used. The present invention includes monoesters and diesters of these astaxanthin isomers.

  In the present invention, the fatty acid ester of astaxanthin may be any of those derived from natural products or those obtained by synthesis, but those derived from natural products in which astaxanthin esters are dissolved in various oils and fats are preferred from absorption in the body. Natural sources include, for example, krill extract, faffia yeast extract, and haematococcus algal extract, but particularly preferred is hematococcus alga extract depending on the stability of astaxanthin and the type of ester of astaxanthin. .

  Fatty acid esters of astaxanthin have not been observed to be mutagenic, are known to be highly safe compounds, and are widely used as food additives (Jiro Takahashi et al .: Toxicity test of hematococcus alga astaxanthin-Ames Test, rat single dose toxicity test, rat 90 day repeated oral dose toxicity test, clinical medicine, 20: 867-881, 2004).

  Haematococcus algae is a green algae belonging to the Volboxic Chlamydomonas family, and since it is a green algae, it has a high chlorophyll content and is green, and it swims in the water with two flagella, but it lacks nutrient sources, changes in temperature, etc. Under starvation conditions, dormant spores are formed, the astaxanthin content is increased, and red spheres are formed. In the present invention, Haematococcus algae in any state can be used, but it is preferable to use Haematococcus algae that have become dormant spores containing a large amount of astaxanthin. In addition, among green algae belonging to the genus Haematococcus, for example, Haematococcus pluvialis is preferable.

  As a method for culturing Haematococcus green algae, a sealed culture method in which foreign microorganisms are not mixed or propagated and other contaminants are not mixed is preferable. For example, a light source is placed in a sealed culture device and light is irradiated from the inside. Culturing using a culture medium having a partially open-type dome-shaped, conical or cylindrical culturing device and a gas discharge device movable within the culturing device, or a flat plate culture tank or tube A method using a culture layer of a mold is suitable.

  The method for obtaining an extract from Haematococcus algae according to the present invention includes a method in which Haematococcus algae is suspended in an organic solvent and pulverized and extracted at the same time, and the Haematococcus algae is dried and pulverized and then extracted with an organic solvent such as acetone or alcohol. And a method of supercritical extraction with a solvent such as carbon dioxide after dry crushing Haematococcus algae.

  The supercritical extraction method can be performed by a conventional method. For example, Hirose (Ind Eng Chem Res, 2006, 45 (10), 3652-3657, Extraction of Astaxanthin from Haematococcus pluvialis Using Supercritical CO2 and Ethanol as Entrainer) Can be done by the method.

  Various methods are known for extracting and purifying the culture or the crustacean using an organic solvent. For example, since astaxanthin and its esters are oil-soluble substances, astaxanthin-containing components can be extracted from natural products containing astaxanthin with an oil-soluble organic solvent such as acetone, alcohol, ethyl acetate, benzene, and chloroform. Further, supercritical extraction can be performed using carbon dioxide, propane, water, or the like. After extraction, the solvent is removed according to a conventional method to obtain a mixed concentrate of monoester type astaxanthin and diester type astaxanthin. The obtained concentrate can be further purified by separation column or lipase decomposition, if desired.

  A method of drying Haematococcus algae cultured in the above-mentioned dome type culture apparatus or closed type culture apparatus, extracting with acetone after pulverization, or performing pulverization and extraction in acetone at the same time, and then removing acetone to extract astaxanthin However, as a result of purifying after purifying by supercritical extraction, there is almost no oxidation of astaxanthin because there is no contact with air, there are few impurities, that is, there are few substances that inhibit the effect of the present invention, and astaxanthin and triglyceride are contained. It can be contained in a large amount with good purity, which is preferable.

  The amount of astaxanthin in the life extension agent / antioxidant function improver of the present invention is an astaxanthin free form equivalent amount, and in adults, 0.0001 to 1 mg, preferably 0.001 to 0.5 mg per kg body weight per day, More preferably, it can mix | blend so that the intake of 0.01-0.2 mg is possible. It can be set as the form divided | segmented so that it can take in multiple times so that these intakes are possible in one day. The dosage varies depending on the age, weight, symptom level, and dosage form of the person being administered. The amount of astaxanthin in the life extension agent / antioxidant function improver of the present invention can be appropriately blended depending on the daily intake, and is contained in an amount of 0.001 to 99% by weight, preferably 0.01 to 90% by weight. Can be made.

  In order to assist the effect of the present invention, a substance having an assist effect can be added. For example, vitamins A; carotenoids (excluding xanthophyll); vitamins B; vitamins C; vitamins D, vitamins E; tocotrienols; glutathione and derivatives thereof and salts thereof; lignans, catechins, anthocyanins, tannins, Polyphenols such as rutin, chlorogenic acid, ellagic acid, curcumin, coumarin; linoleic acid, α- or γ-linolenic acid, arachidonic acid, eicosapentaenoic acid, succinic acid, docosahexaenoic acid and their derivatives and salts thereof; collagen, elastin , Fibronectin, keratin proteins and their derivatives and hydrolysates; alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine Amino acids such as syn, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine and their derivatives and salts thereof; peptides; α- such as glycolic acid, lactic acid, malic acid, citric acid, salicylic acid Hydroxy acids and their derivatives and salts thereof; serum deproteinization, spleen, placenta, chicken crown, royal jelly, yeast, lactic acid bacteria, bifidobacteria, ganoderma, carrot, assembly, rosemary, agar, garlic, hinokitiol, cephalanthin, aloe, Salvia, Arnica, Chamomile, Birch, Hypericum, Eucalyptus, Mukuroji, Sempokuka, Caquette, Sunpens, Sakuhaku, Toki, Ibukitorano, Clara, Hawthorn, Shirayuri, Hop, Neubara, Yokuinin, Do Natural products such as Dami, Seaweed, Natto, Lemongrass, Hibiscus and their extracts; Adenylic acid derivatives such as adenosine triphosphate, adenosine diphosphate, adenosine monophosphate; iron, vanadium, molybdenum, manganese, copper, Minerals such as potassium, magnesium, calcium, zinc, selenium, iodine; monosaccharides such as mannitol, xylitol, glucosamine; hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, keratan sulfate, glycogen, chitin, chitosan, etc. Polysaccharides; Nucleic acids such as deoxyribonucleic acid and ribonucleic acid; Other glycyrrhizic acid, guanine, mucin, ubiquinone, α-lipoic acid, octacosanol, allicin, alliin, raspberry ketone, capsiate, honey, royal jelly, cap Such as leucine, and it can be selected from the group consisting of a mixture thereof alone or in combination. These components are generally blended in an amount of 0.01 to 90% by weight, preferably 0.1 to 50% by weight, based on the total amount of the pharmaceutical, and can be used in combination of one or more.

  The life extending agent / antioxidant function improving agent of the present invention can be blended or taken in medicines, foods and drinks, cosmetics, and feeds. In the present invention, the drug includes quasi-drugs in addition to the drug.

  The pharmaceutical containing the life extension agent / antioxidant function improving agent of the present invention may contain an appropriate amount of various additives used for production of general preparations. Examples of such additives include excipients, binders, acidulants, foaming agents, artificial sweeteners, fragrances, lubricants, colorants, stabilizers, pH adjusters, and surfactants. Excipients include, for example, corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, porous starch, and other sugars, lactose, sucrose, glucose and other sugars, mannitol, xylitol, Examples thereof include sugar alcohols such as erythritol, sorbitol, maltitol, magnesium aluminate metasilicate, hydrotalcite, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, and light anhydrous silicic acid. Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gum arabic powder, gelatin, and pullulan. Examples of the disintegrant include starch, agar, carmellose calcium, sodium carboxymethyl starch, croscarmellose sodium, crospovidone, crystalline cellulose, and F-MELT (trademark, manufactured by Fuji Chemical Industry Co., Ltd.). Examples of sour agents include citric acid, tartaric acid, malic acid, ascorbic acid and the like. Examples of the foaming agent include sodium bicarbonate and sodium carbonate. Examples of the sweetener include saccharin sodium, dipotassium glycyrrhizin, aspartame, stevia and thaumatin. Examples of the fragrances include lemon oil, orange oil, menthol and the like. Examples of the lubricant include magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearic acid, and sodium stearyl fumarate. Examples of the colorant include edible pigments such as edible yellow No. 5, edible red No. 2, and edible blue No. 2, edible lake pigments, and iron sesquioxide. Examples of the stabilizer include sodium edetate, tocopherol, cyclodextrin and the like. Examples of the pH adjuster include citrate, phosphate, carbonate, tartrate, fumarate, acetate, amino acid salt and the like. Examples of the surfactant include polysorbate 80, methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyoxyethylene sorbitan monolaurate, gum arabic, and powdered tragacanth. In order to improve the absorption and formulation of astaxanthin and tocotrienol, it can be in a powder state.

  For syrups, drinks, suspensions, eye drops, injections and other liquids, active ingredients are adjusted to pH, buffers, solubilizers, suspensions, etc., as required, tonicity agents, stabilizers, antiseptics It can be formulated by a conventional method in the presence of an agent. Examples of the suspending agent include polysorbate 80, methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyoxyethylene sorbitan monolaurate, gum arabic, and powdered tragacanth. Examples of the solubilizer include polysorbate 80, hydrogenated polyoxyethylene castor oil, nicotinamide, polyoxyethylene sorbitan monolaurate, macrogol, and castor oil fatty acid ethyl ester. Examples of the stabilizer include sodium sulfite and sodium metasulfite. Examples of the preservative include methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, sorbic acid, phenol, cresol, chlorocresol and the like.

  There are no particular limitations on the form of the external preparation for skin, for example, cosmetics such as emulsions, creams, lotions, packs, dispersions, cleaning agents, makeup cosmetics, scalp / hair products, ointments, creams, and external use. It can be a pharmaceutical such as a liquid. In addition to the above components, components commonly used in skin external preparations such as cosmetics and pharmaceuticals, such as whitening agents, moisturizers, various skin nutritional components, ultraviolet absorbers, antioxidants, oily components, surfactants, thickeners , Alcohols, coloring agents, water, preservatives, fragrances and the like can be appropriately blended as necessary.

  As food and drink, it can be used as supplements, functional health foods, special-purpose foods, health foods, general foods, beverages, and it is easy to determine the intake and intake, so supplements, health functional foods, special-purpose foods And can be ingested in the same form as the aforementioned pharmaceuticals, solid dosage forms such as tablets, intraoral quick disintegrating tablets, capsules, granules, fine granules, etc., and liquid dosage forms such as syrups and suspensions. Among ingredients used in the above pharmaceutical preparations, those that can be used in foods can be selected, in addition to milk protein, soy protein, egg albumin protein, etc., or egg white oligopeptide, soy hydrolyzate that is a degradation product thereof, A mixture of amino acids alone can also be used in combination. In addition, when provided in the form of a drink, nutritional additives such as amino acids, vitamins and minerals, sweeteners, spices, fragrances, and pigments may be added to improve the nutritional balance and flavor during intake. Good. The form of the food or drink of the present invention is not limited to these.

  In the present invention, the functional food is a food having a medicinal effect that is permitted or specified by the government or a public body. For example, a functional food such as a nutritional functional food or a food for specified health use, a special-purpose food. Etc. In addition, although a name and a rule change with situations and times, what is essentially the same is included in the present invention. This includes packages and containers that display medicinal benefits, and foods that contain explanatory documentation.

  Examples of forms of general foods, ie, foods and drinks include margarine, butter, butter sauce, cheese, fresh cream, shortening, lard, ice cream, yogurt, dairy products, sauce products, fish products, pickles, natto, boiled beans, fried beans , Tofu, mapo tofu, mixed nuts, french fries, potato chips, snacks, kakimochi, popcorn, sprinkle, chewing gum, chocolate, pudding, jelly, gummy candy, candy, drop, caramel, bread, castella, cake, donut, Biscuits, cookies, crackers, baked goods, macaroni, pasta, ramen, buckwheat, udon, salad oil, instant soup, dressing, eggs, mayonnaise, miso, etc. or carbonated drinks such as fruit juice drinks, soft drinks, sports drinks or Such as carbonated beverages, may tea, coffee, non-alcoholic or liqueur, alcoholic beverages such as medicinal liquor, such as cocoa, energy drinks, milk, be added examples of the general foods such as soy milk.

  In food and drink, astaxanthin is blended together with raw materials for general foods, and is manufactured by processing according to a conventional method. The amount of astaxanthin varies depending on the form of the food and is not particularly limited. In general, the amount of astaxanthin used can be appropriately selected by those skilled in the art depending on the type of food and drink, and the above amounts can be blended. .

  Even when the life extension agent / antioxidant function improver of the present invention is added to a feed, the same effect as that of a pharmaceutical or food and drink can be obtained. For example, a mouse, a hamster, a rat, a rabbit, a dog, a cat, a pig, It can be administered to cattle, horses, sheep, monkeys, birds, crocodiles, snakes, frogs, goldfish and the like.

  When administered to animals, ingestion of 0.0001 to 1 mg, preferably 0.001 to 0.5 mg, more preferably 0.01 to 0.2 mg per kg of body weight per day per kg of body weight per day It can be blended so that the amount is possible.

  The feed of the present invention is in the form of a solid preparation, solid, pellet, granule, biscuit, kneaded, etc., and dry food, semi-dry food (for example, feed having a water content of about 10 to 50% by weight), or wet such as canned food It is not particularly limited to food (for example, feed having a water content of about 50 to 80% by weight). In the process of conventional feed production, astaxanthin can be produced by adding one or more kinds of astaxanthin to the feed material and mixing them, or astaxanthin by sprinkling one or more aqueous solutions on the feed. The feed of the present invention can also be prepared by adding and mixing one or more astaxanthins to a commercially available feed or sprinkling them. Also, like human dietary supplements, it should be manufactured with solid preparations such as tablets, sublingual tablets, pills, powders, powders, fine granules, granules, capsules and soft capsules that are easy to ingest. Can do.

  There are no particular restrictions on the ingredients that can be used as long as they can be used as feed, but feed ingredients that are commonly used depending on the type of feed, such as fish meal, fish, seafood, fishmeal, and livestock meat. Animal raw materials such as meat powder, meat and bone meal, blood meal, feather meal, cocoon oil cake, skim milk powder, animal fats (beef oil, pork oil, bone oil, etc.), eggs, milk, etc .; beer yeast, torula yeast, etc. Microorganisms; corn, milo, wheat, barley, rye, oats, wheat flour, brown rice, millet, soybeans, quinako, cassava and other cereals; pregelatinized starch, starches such as starch; soybean oil cake, molted soybean oil cake, rapeseed oil cake, Oil pods such as peanut oil coconut, palm oil cocoon, sunflower oil cocoon, linseed oil cocoon, sesame oil cocoon, safflower oil cocoon, palm kernel oil cocoon, kapok oil cocoon; rice bran, barley bran, bran Nuka's; Grun feed, gluten meal, starch cake, honey, soy sauce cake, beer cake, beet pulp, bagasse, tofu cake, malt root, citrus peel, tangerine juice cake, etc .; alfalfa meal, timothy hay, Fibrin such as koji; excipients, binders, disintegrants, saccharides such as salt and sugar, vitamins, amino acids, minerals and other components can be used alone or in combination.

  As a raw material which can be blended in a solid preparation, in addition to the above-mentioned raw materials, for example, it can be produced by uniformly mixing with a carrier generally used in the human food field. Specifically, sugars such as sucrose, sorbitol and fructose, glycols such as polyethylene glycol and propylene glycol, oils such as sesame oil, rapeseed oil, olive oil and soybean oil, and flavors such as strawberry flavor and peppermint Can be manufactured using. Also in the form of powders, pills, capsules, soft capsules, tablets, excipients such as lactose, glycolose, sucrose, lactose, mannitol, corn starch, silicon dioxide, disintegrants such as starch and sodium alginate, magnesium stearate Lubricants such as talc, binders such as polyvinyl alcohol, hydroxypropyl cellulose, gelatin and casein, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, saponins, lecithin and other emulsifiers, guar gum, alginic acid, carrageenan, agar , Pectin, gum arabic, and thickeners such as crystalline cellulose, and plasticizers such as glycerin. As the tablet type, tablets and soft capsules are preferable because they are easy to ingest.

  In order to describe the present invention in more detail, examples will be given below, but the present invention is not limited to these examples.

[C. Survival number test by elegans]
An NGM agar medium was prepared, sterilized by autoclaving, and then cooled to below 60 ° C. Add a suitable amount of 0.1M astaxanthin (Sigma, purity> 98%) in DMSO to make an NGM agar medium containing astaxanthin with final concentrations of 0 mM, 0.1 M, and 1.0 mM, and transfer to a 3.5 cm petri dish. The medium was completed. One drop of Escherichia coli (OP50) serving as food was dropped on this agar medium and left overnight to complete an astaxanthin-containing NGM agar medium with food.
C. elegans in synchronized culture About 500 elegans L1 larvae were transferred to a 9 cm plate of NGM agar medium coated with food and cultured at 20 ° C. The date of transfer was designated as the first day. About 800 μl of a 0.5 mg / ml FUdR solution was added dropwise to the adult larvae on the 4th day in order to suppress hatching and migration of next-generation larvae.
On the 5th day, about 80 μl of 0.5 mg / ml FUdR solution was dropped onto a 3.5 cm plate of astaxanthin-containing NGM agar medium prepared as described above, and 10 adults were transferred with a platinum wire to measure one life. About 100 nematodes were used per one. In order to prevent drying, plates with nematodes were placed in a plastic box and incubated at 20 ° C. until the last one died.
Nematode viability was determined every other day under a stereomicroscope. The results are shown in Table 1 and FIGS.

実施例の平均寿命はそれぞれ対象群（比較例）に対して効果があった。（Ｐ＜０．０１） [Table 1] Life of nematodes

The average lifespan of the examples was effective for the target group (comparative example). (P <0.01)

  From Examples 1-4 and Comparative Examples 1-2, it can be seen that both wild strain (N2) and long-lived strain (age-1) have a significant life-extending effect depending on the dose of astaxanthin. . In addition, from the results of FIG. 3 of the long-lived strain (age-1), the maximum life of each administration group is 73 to 77 days, and the average life is extended by 4 to 8 days. It shows that the effect of extending healthy life is more effective.

[C. elegans SOD gene activity]
Wild strains (N2) and long-lived strains (age-1) were bred for 14 days under the same conditions as in Examples 2 and 4. C. The elegans was taken out and polished, and poly (A) ⁺ RNA was prepared using RT-PCR (manufactured by Invitrogen), cDNA was synthesized by reverse transcription reaction, and then polymerase chain reaction (PCR) was performed. . Next, after staining the PCR product fragment with ethidium bromide, perform agarose gel electrophoresis, photograph the DNA fragment with a photometer LAS-4000UVmini (manufactured by Fujifilm), perform optical analysis, and measure the fluorescence intensity. did.

[Table 2] Expression intensity of SOD gene

  From Examples 5-6 and Comparative Examples 3-4, it can be seen that various SOD genes are activated by ingesting astaxanthin in both the wild strain (N2) and the long-lived strain (age-1). Since the SOD gene activity is higher in the long-lived strain than in the wild strain, C.I. One of the causes of the life extension effect of elegans is an increase in SOD activity.

[Production Example 1] Tablet According to a conventional method, the following ingredients were uniformly mixed and tableted at the following composition ratio to give a tablet of 400 mg per tablet.
Asteryl powder 20F 25 parts by weight Powdered cellulose 42 parts by weight Reduced malt syrup 17 parts by weight Agar 12 parts by weight Silicon dioxide 1 part by weight Sucrose fatty acid ester 3 parts by weight Asteryl powder 20F [manufactured by Fuji Chemical Industry Co., Ltd.] is free It is a powder containing 2% by weight of astaxanthin in terms of conversion.

[Formulation Example 2] Capsules According to a conventional method, 100 mg of soft capsule skin (70 parts by weight of gelatin, 25 parts by weight of glycerin) was kneaded with 300 mg of the following ingredients and filled to obtain 440 mg of soft capsules.
Contents Asteryl oil 50F 30 parts by weight Medium chain fatty acid triglyceride 70 parts by weight Asteryl oil 50F (manufactured by Fuji Chemical Industry Co., Ltd.) is an extract of Haematococcus alga containing 5% by weight of astaxanthin in terms of free form.

[Formulation Example 3] Drink agent The following ingredients were blended, and water was added to 10 L according to a conventional method to prepare a drink agent.
Water-soluble astaxanthin solution 50g
Royal Jelly 1g
Liquid sugar 1000g
DL-sodium tartrate 1g
Citric acid 10g
Vitamin C 10g
Vitamin E 20g
25 g of cyclodextrin
Potassium chloride 2g
Magnesium sulfate 1g
A water-soluble astaxanthin solution [manufactured by Fuji Chemical Industry Co., Ltd.] is obtained by making an aqueous solution of Haematococcus alga extract oil containing 0.5% by weight of astaxanthin in terms of free form.

[Formulation Example 4] Bar-shaped baked confectionery In accordance with a conventional method, a dough blended with the following components was prepared, molded into an appropriate bar-shaped form, and then baked in an oven at 170 ° C. for 15 minutes to prepare a bar-shaped baked confectionery.
Asterel powder 20F 2 parts by weight Raspberry powder 2 parts by weight Butter 20 parts by weight Sugar 20 parts by weight Salt 0.1 part by weight Egg 25 parts by weight Flour 72 parts by weight Flavor Suitable amount Milk 5 parts by weight

Claims (6)

Life extension agent containing astaxanthin as an active ingredient. The life extension agent according to claim 1, wherein the life extension is an extension of a healthy lifespan. An in vivo antioxidant function improver comprising astaxanthin as an active ingredient. The life extension agent or antioxidant function improver according to any one of claims 1 to 3, wherein the dose of astaxanthin per kg body weight per day is 0.0001 to 1 mg. Use of astaxanthin for producing the form of the life extending agent or antioxidant function improving agent according to any one of claims 1 to 4 into a tablet, capsule or aqueous solution. Use of the life extending agent or antioxidant function improving agent according to any one of claims 1 to 4 as a food or drink.

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