JP2012246244A - Capillary regression inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an improving agent of capillary regression generated from a disorder of an organ or an internal organ such as various diseases or injuries, and further to improve the capillary regression, to thereby heighten speed of treatment/improvement of various diseases or various disorders of organs.SOLUTION: Capillary regression can be improved by using as an active constituent, astaxanthin synthesized or extracted from Haematococcus alga, Phaffia yeast or the like. The improving agent of capillary regression contains astaxanthin as much as 0.001-100 mg per day.

Description

  The present invention relates to an astaxanthin active ingredient and a capillary regression inhibitor.

  In various diseases and injuries, organ regression often occurs. Once injuries and illnesses have recovered, it takes much longer time for rehabilitation of organs and organs. In recent years, shortening these periods has become an issue. So far, methods for promoting regeneration / neogenesis of destroyed sites have been studied for organ / organ recovery. For example, administration of components related to growth, exercise therapy such as therapeutic exercises, and rehabilitation such as physical therapy have been performed.

  In the treatment of diseases and injuries, shortening the recovery period by rehabilitation of organs and organs after healing has been studied by suppressing the regression of organs and organs during the progress of damage due to diseases and injuries. . In the function of recovery from organ / organ regression, tissue (cells) such as apoptosis occurs during regression due to injury, and during recovery tissue regeneration, capillaries are formed in the tissue, and tissue cells are formed and grown The organs and tissues recover.

  For example, due to injuries such as fractures and diseases, bed rest for a long time results in disuse muscle atrophy and the muscle tissue regresses. Long-term rehabilitation is required to restore muscle tissue after the injuries and illnesses that cause it have been improved and treated. In disuse muscular atrophy of muscular tissue, regression and disappearance of muscular tissue (cells) itself and capillaries are caused by apoptosis and the like. When disuse muscular atrophy improves to normal, capillaries will stretch into the muscle tissue, resulting in an increase in muscle tissue and recovery.

  Further, in the operation of organs and organs, not only the cut surface but also the nearby tissues are regressed by cutting the organ. At the time of recovery of the organ, a new capillary network and new organ cells are generated in the destroyed tissue, and the organ is recovered.

  On the other hand, 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, yeasts such as red yeast faffia, etc. It is known that it has an antioxidant action about 1000 times that of vitamin E and about 40 times that of β-carotene, and has an anti-inflammatory effect (Patent Document 1).

JP-A-2-49091

  In order to promote recovery from the regression of an organ due to an injury such as a disease or injury, an inhibitor of vascular regression is required.

  As a result of intensive studies to achieve the above-mentioned object, the present inventors have the effect of suppressing the regression of blood vessels in organs and organs, particularly capillary blood vessels, due to injury such as diseases and injuries by administering astaxanthin. As a result, the present invention was completed.

  Administering astaxanthin in the form of pharmaceuticals as an active ingredient suppresses the regression of capillaries in organs and organs due to injuries such as diseases and injuries, and shortens the organs and organs recovered after the injury is removed Can do.

2 is a cross-sectional photograph of muscle tissue taken to measure the number of capillaries in Example 1. FIG. It is the figure which showed the number of capillaries with respect to the muscle fiber of Example 1, and its ratio (Tables 3 and 4). 3 is a three-dimensional image of capillaries photographed to measure the capillaries volume and diameter of Example 1. FIG.

  The present invention is a vascular regression inhibitor containing astaxanthin as an active ingredient. In order to enhance this effect, a substance having an auxiliary effect described later can be added. It is possible to shorten the recovery period from injury, disease, and disuse injury caused by them.

  The blood vessel regression is a reduction or disappearance of blood vessels of the tissue, particularly capillary blood vessels, which occurs in parallel with the tissue regression due to injury or disease to the body tissue. Examples of body tissue injuries include tissue destruction and cutting due to injury, excision and incision by surgery, fixation of limbs, bedridden, and disuse injuries due to life in a weightless state. Diseases include diseases associated with tissue destruction such as hepatitis, kidney damage, heart disease, and brain disease.

  Suppression of vascular regression is suppression of vascular regression due to the aforementioned tissue damage. A distinction is made from the improvement and treatment of injury and disease. In the improvement and treatment of injuries and diseases, these causes are removed to improve and treat tissue injuries and diseases, and then the tissue that has been destroyed or reduced by the inherent healing power of the living body is regenerated. In tissue regeneration, capillary hair is first born, and tissue cells are increased simultaneously. Therefore, regeneration of the capillary network that transports various nutrients occupies an important factor for regeneration. By suppressing the regression of these organs / capillaries of the organs, the tissue recovery period can be shortened.

  The blood vessels in the present invention are capillaries that transport nutrients directly to tissue cells in tissues, and do not include aorta or veins that transport blood between organs. Conventionally known astaxanthin has a different action from arteriosclerosis and vascular dysfunction improvement.

  The inhibitory effect of astaxanthin on vascular regression in the above-mentioned damaged tissue can be considered to be effects such as suppression of vascular regression factors, increase of angiogenic factors, or reduction of factors that directly damage blood vessels.

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; monovalent 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 hermetically sealed culture method is preferred in which no foreign microorganisms are mixed and propagated and other contaminants are not mixed. For example, a partially open-type dome shape, conical shape or cylindrical shape is preferable. A culture method using a culture medium having a culture apparatus and a gas discharge device movable within the apparatus (International Publication No. 99/50384), or culturing by irradiating light from inside a sealed culture apparatus And a method using a flat culture tank or a tube-type culture layer are suitable.

  The method for obtaining an extract from Haematococcus algae according to the present invention includes a method in which Haematococcus algae is dried and pulverized and then extracted with an organic solvent such as acetone or alcohol, and the Haematococcus algae is suspended in an organic solvent and pulverized and extracted simultaneously. Or a supercritical extraction method using carbon dioxide or the like.

  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 compounding amount of astaxanthin in the vascular regression inhibitor of the present invention is an astaxanthin free body equivalent amount, and for adults, 0.0001 to 100 mg, preferably 0.001 to 50 mg, more preferably 0.01 per kg body weight per day. It can mix | blend so that the intake of -1 mg, more preferably 0.01-0.2 m 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 patient to be administered. The amount of astaxanthin in the vascular regression inhibitor of the present invention can be appropriately blended depending on the daily intake, and can be contained in an amount of 0.001 to 99% by weight, preferably 0.01 to 90% by weight.

  The vascular regression inhibitor of the present invention is administered during the treatment of normal injury, disuse injury or disease. It is not necessary to administer after the removal of the cause and the progression has stopped.

  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 astaxanthin); 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, isolo Amino acids such as isine, 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, Natural products such as kudami, seaweed, natto, lemongrass, hibiscus and their extracts; adenylate 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, caps Latest, and may 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 vascular regression inhibitor, and can be used in combination of one or more.

  The vascular regression inhibitor of this invention can be mix | blended with food-drinks, cosmetics, and feed. In the present invention, the vascular regression inhibitor includes quasi drugs.

  The vascular regression inhibitor of the present invention may contain appropriate amounts of various additives used in the 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.

  The form of the external preparation for skin is not particularly limited, for example, forms of external preparations such as ointments, creams, external preparations, emulsions, creams, lotions, packs, dispersions, cleansing agents, makeup cosmetics, It can be made into cosmetics such as scalp products. In addition to the above components, components used in external preparations for skin and normal cosmetics, such as whitening agents, moisturizers, various skin nutritional components, UV absorbers, antioxidants, oily components, surfactants, thickeners, alcohols Coloring agents, water, preservatives, fragrances and the like can be appropriately blended as necessary.

  The skin is always exposed to the outside and is subjected to various stresses such as oxidation and ultraviolet rays, and is always in a mild injury state. In the external preparation for skin of the present invention, it is possible to suppress capillary regression of the skin and to suppress deterioration of the skin condition.

  As a food or drink containing the vascular regression inhibitor of the present invention, it can be used as a supplement, a functional health food, a special-purpose food, a health food, a general food, a beverage, and since it is easy to determine the intake and the amount of intake, Supplements, functional health foods, and special-purpose foods are preferred, in the same form as the above-mentioned vascular regression inhibitor, solid dosage forms such as tablets, intraoral rapidly disintegrating tablets, capsules, granules, fine granules, syrups and suspensions, etc. It can be taken in liquid dosage form. Among ingredients used in the above preparation for vascular regression, those that can be used in foods can be selected. In addition, milk protein, soy protein, egg albumin protein, etc., or egg white oligopeptide, soy hydrolyzate, which is a degradation product thereof, can be selected. A decomposition product or 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 an effect as a vascular regression inhibitor that is permitted / designated by the government or a public organization, for example, a health functional food such as a nutritional functional food or a food for specified health use, Special foods. In addition, although a name and a rule change with situations and times, what is essentially the same is included in the present invention.

  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. .

  The same effect can be obtained even when administered to animals other than humans as feed. Examples of animals include mice, hamsters, rats, rabbits, dogs, cats, pigs, cows (especially Japanese black beef), horses, sheep, monkeys, 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.

  As a feed form of the food and drink of the present invention, a solid preparation, a solid form, a pellet form, a granular form, a biscuit form, a kneaded form and the like, a dry food, a semi-dry food (for example, a feed having a water content of about 10 to 50% by weight), Alternatively, it is not particularly limited to wet food such as canned 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. Moreover, it can manufacture with solid preparations, such as a tablet, a pill, a powder, a powder, a fine granule, a granule, a capsule, and a soft capsule which are easy to ingest like a human dietary supplement.

  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.

[Example 1]
Twenty-four mature Wistar male rats (12 years old) were divided into a control group (CONT group, n = 7), a hind limb unloaded group (HU group, n = 7), a hind limb unloaded group + nutrition support group (HU + NS group, n = 7) divided into 4 groups. HU group and HU + NS group were unloaded with hind limbs by tail suspension, and HU + NS group was administered astaxanthin (50 mg / kg, manufactured by Fuji Chemical Co., Ltd., extract from Haematococcus alga) twice a day using a sonde. Administered. After continuing the experiment for 7 days, the left soleus muscle was removed and the number of capillaries was measured, and the right soleus muscle was removed and a capillary three-dimensional image was measured.

[Table 1] Test group

(Soleus muscle weight)
The muscle wet weight of the extracted soleus was measured.

[Table 2] Body weight and soleus muscle wet weight

(Measure the number of capillaries)
The extracted left soleus muscle was snap frozen and thin sections were prepared and subjected to alkaline phosphoase staining. Photographs were taken with a microscope, and the ratio of muscle fibers and capillaries per unit area of the soleus muscle (ratio of the number of capillaries to muscle fibers (C / F ratio)) and the number of capillaries per muscle fiber were determined.

[Table 3] Ratio of number of capillaries to muscle fibers (C / F ratio)

[Table 4] Number of capillaries per muscle fiber

(3D structure analysis of capillaries)
Carrageen was inserted into the abdominal aorta, perfused with heparinized saline, and then a fluorescent contrast agent was perfused at a pressure of 120 mmHg, and then the right soleus was removed. A three-dimensional capillary image was constructed with a confocal laser microscope, and the capillary volume and capillary diameter were measured. The measured values were subjected to a one-way analysis, and the Tukey test was used for the post-hoc test. The significance level was less than 1%.

[Table 5] Capillary volume

[Table 6] Capillary diameter

  Muscle wet weight was significantly reduced in the HU group and the HU + NS group compared to the CONT group. The ratio of the number of capillaries to muscle fibers (C / F ratio), the number of capillaries around the muscle fibers, and the capillarity volume were significantly reduced in the HU group compared to the CONT group. On the other hand, in the HU + NS group in which astaxanthin was administered to the HU group, the C / F ratio and the number of capillaries around the muscle fibers were not different from those in the CONT group, and the capillary diameter was lower than that in the CONT group. However, the value was significantly higher than that of the HU group. Capillary blood vessel volume was significantly higher than that in the HU group, and no difference from the CONT group was observed.

  In the HU group, as a result of the indices related to capillaries (C / F ratio, number of capillaries around muscle fibers, capillar volume, and capillar diameter) in the skeletal muscle, capillar regression occurred and HU + NS administered astaxanthin In the group, capillary regression could be suppressed.

Claims (7)

Capillary regression inhibitor containing astaxanthin as an active ingredient. The capillary regression inhibitor according to claim 1, which is astaxanthin produced from Haematococcus algae. The capillary regression inhibitor according to any one of claims 1 and 2, wherein the dose of astaxanthin per kg body weight per day is 0.001 to 100 mg. 4. The capillary regression inhibitor according to any one of 1 to 3, wherein the administration period of astaxanthin is under treatment of injury or disease accompanied by tissue regression. The capillary regression inhibitor according to any one of claims 1 to 4, comprising astaxanthin and the following adjuvant;
Vitamins A, carotenoids (excluding astaxanthin), vitamins B, vitamins C, vitamins D, vitamins E, tocotrienols, glutathione and their derivatives and salts thereof; catechins, anthocyanins, flavangenols, tannins, Polyphenols selected from rutin, isoflavone, chlorogenic acid, ellagic acid, curcumin, coumarin, lignan; linoleic acid, α- or γ-linolenic acid, arachidonic acid, eicosapentaenoic acid, succinic acid, docosahexaenoic acid and their derivatives and their derivatives Salts; proteins selected from collagen, elastin, fibronectin, keratin and their derivatives and hydrolysates; alanine arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid , Glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, taurine and their derivatives and salts thereof, peptides; glycolic acid, lactic acid, malic acid, Α-hydroxy acids selected from citric acid and salicylic acid and derivatives thereof, and salts thereof; serum deproteinization, spleen, placenta, chicken crown, royal jelly, yeast, lactic acid bacteria, bifidobacteria, ganoderma, carrots, assembly, rosemary, amber , Garlic, hinokitiol, cephalanthin, aloe, salvia, arnica, chamomile, birch, hypericum, eucalyptus, mukuroji, sempukuka, keiketou, sunpens, suhakuhi, touki, ibukitorano, clara, Natural products selected from nashi, shirayuri, hops, neubara, yokuinin, dokudami, seaweed, natto, lemongrass, hibiscus and their extracts; adenylic acid selected from adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate Derivatives: Minerals selected from iron, vanadium, molybdenum, manganese, copper, potassium, magnesium, calcium, zinc, selenium, iodine and solid solutions thereof; lactose, mannitol, erythritol, xylitol, glucosamine, hyaluronic acid, chondroitin sulfate, dermatan Saccharides selected from sulfuric acid, heparan sulfate, heparin, keratan sulfate, glycogen, chitin, chitosan, mucosaccharides; lignans selected from sesamin and flax lignans: deoxyribonucleic acid, ribonucleic acid, glycyrrhizic acid , Guanine, mucin, ubiquinone, α-lipoic acid, octacosanol, allicin, alliin. A method for using astaxanthin for producing a tablet or capsule for the purpose of suppressing capillary regression. The use method according to claim 6, wherein astaxanthin is obtained from Haematococcus algae, and 0.001 to 100 mg of astaxanthin per kg of body weight per day is contained as an effective amount for suppressing vascular regression.

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