JP2008239619A - Peripheral blood circulation ameliorative composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a peripheral blood circulation ameliorative composition affecting no influence on blood pressure and enabling blood circulation to be efficiently increased in peripheral blood vessels. <P>SOLUTION: The peripheral blood circulation ameliorative composition contains astaxanthin and lignin at such levels that the astaxanthin's daily dose is 0.01-20 mg and the lignin's daily dose is 0.1-1,000 mg. Food or feed containing this peripheral blood circulation ameliorative composition is also provided. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a composition having an effect of improving peripheral blood circulation disorders using xanthophyll and lignan as active ingredients. More specifically, the present invention relates to a composition having an effect of improving peripheral blood circulation disorders, comprising as an active ingredient an extract obtained from Haematococcus algae containing astaxanthin and a linseed extract containing linseed lignan. In addition, the present invention relates to pharmaceuticals, foods, and functional foods containing a peripheral blood injury-improving composition.

  In recent years, speeding up of social changes, changes in lifestyle habits due to satiety and lack of exercise and increased stress have been regarded as problems, and metabolic syndrome such as hypertension, hyperglycemia, increased neutral fat and cholesterol in the blood, etc. In addition, blood circulation disorders such as eye strain, stiffness and pain in the neck and shoulders due to stress, low back pain, and coldness are increasing. Even if they do not become life existence or a serious disability, they can become a disability in one circle of life, resulting in a decrease in QOL (quality of life) and numbness and insomnia when symptoms are severe.

  In particular, the automation of work in the industry is progressing at a rapid rate, and most of the office work is done with computers, and many people other than occupations specializing in computer work such as system engineers and programmers take a long time. Have come to use. It is said that more than 70% of workers who use computer equipment in their work complain of physical fatigue and subjective symptoms, and half of them complain of neck / shoulder stiffness / pain. It is an important problem that causes a decline.

  Until now, as a method for improving peripheral blood circulation, appropriate exercise and intake of beneficial ingredients have been performed. Tocopherols, polyphenols, chitosan, ginkgo biloba extract, CoQ10, folic acid and the like have been used as effective in improving peripheral blood circulation. However, the effect of improving peripheral blood circulation, such as the need for large intakes and regular intakes, was not satisfactory.

  Xanthophyll is a natural and widely distributed yellow to red pigment, and is used as a pigment in foods and cosmetics. In particular, astaxanthin has a high antioxidant capacity and approximately 1000 times the antioxidant capacity of vitamin E, so it has the effect of improving antioxidants in the body and the regulation of eyes, improving metabolic syndrome, reducing aging, and improving blood flow. There are known effects (Patent Document 1) and having an anti-stress effect (Patent Document 2).

  Lignans are low-molecular-weight condensates of phenylpropane units, such as secoisolariciresinol glycoside (SDG) contained in flax seed, sesamin contained in sesame seed, and the like. These are known to have effects similar to those of estrogen, a cancer suppressing action, an anti-inflammatory effect, an active oxygen scavenging effect (Patent Document 3), and the like.

  To date, xanthophyll and lignan are rich in food, safe with no side effects for a long time, and each is known to have an effect of improving peripheral blood circulation alone, but it contains xanthophyll and lignan. It is not known that each product has a peripheral blood circulation improving effect superior to that administered alone.

Japanese Special Reissue WO02 / 094253 Japanese Unexamined Patent Publication No. 9-124470 Japanese Unexamined Patent Publication No. 9-208461

  As a result of searching for substances that improve peripheral blood circulation disorders, the present inventors have found that a composition containing xanthophyll and lignan has an excellent effect of improving peripheral blood circulation disorders. The present invention has been completed based on such findings, and provides a peripheral blood circulation disorder composition containing xanthophyll and lignan as active ingredients, and a pharmaceutical product and food and drink containing the peripheral blood circulation disorder composition.

  As a result of intensive studies to solve the above problems, the present inventors have found that a composition containing xanthophyll and lignan has a marked improvement in peripheral blood circulation disorders. The present invention is based on such knowledge.

  By ingesting the peripheral blood circulation disorder improving composition of the present invention in the form of pharmaceuticals, foods, etc., it is possible to improve the blood circulation of the site causing peripheral blood circulation disorder, and by this peripheral blood circulation improvement, muscle tone disorders such as stiff shoulders Can improve the quality of life.

  In the present invention, xanthophylls are astaxanthin, zeaxanthin, lutein, cryptoxanthine, tunaxanthin, salmoxanthine, parasiloxanetin, violaxanthin, anthaxanthin, cucurbitaxanthin, diatoxanthine, alloxanthin, pectinol, pectinolone, and mactra. Xanthine, capsanthin, capsanthinol, fucoxanthin, fucoxanthinol, peridinin, halocinthiaxanthine, amarosiaxanthine, canthaxanthin, echinone, rhodoxanthine, bixin, norbixin, preferably astaxanthin, cryptoxanthin, zeaxanthin , Lutein, canthaxanthin, capsanthin, fucoxanthin, particularly preferably astaxanthin That. As these xanthophylls, those extracted from natural products such as plants, animals, microorganisms, and chemically synthesized products can be used. Extracts of substances from natural products are not particularly limited in terms of raw material type, production area and production method.

  In the description of the present invention, xanthophyll includes xanthophyll and / or its ester unless otherwise specified. Furthermore, the ester of xanthophyll includes a monoester form and / or a diester form.

  As the xanthophyll of the present invention, at least one of xanthophyll 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 in the composition of the present invention. 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 xanthophyll by the in vivo enzyme and exhibits an effect.

  Examples of the monoester of xanthophyll 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 , Stering acid, dodecenoic acid, oleic acid, stearic acid, eicosaopentaenoic 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, xanthophyll 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.

  As the diester of xanthophyll, the group consisting of the lower saturated fatty acid, higher saturated fatty acid, lower unsaturated fatty acid, higher unsaturated fatty acid, amino acid, monovalent 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 seafood, alpha-proteobacteria such as Paracoccus sp. N81106, Brevundimonas sp. SD212, Erythrobacter sp. PC6, and 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, as the fatty acid ester of astaxanthin, any of those derived from natural products or those obtained by synthesis can be used, but those derived from natural products in which the astaxanthin ester is dissolved in various oils and fats are preferred from absorption in the body. Natural sources include, for example, a krill extract, a faffia yeast extract, and a hematococcus alga extract. Particularly preferred is a 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, hematococcus in any state can be used, but it is preferable to use hematococcus that has 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 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 extraction and purification from 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. Also, supercritical extraction can be performed using carbon dioxide, 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 (Japanese Patent Laid-Open No. 2006-70114) has almost no oxidation of astaxanthin because it does not come into contact with air, and there are few impurities, that is, there are few substances that inhibit the effect of the present invention, and it contains astaxanthin and triglycerides in high purity. This is preferable.

  In the present invention, a lignan is a low molecular weight substance or a derivative thereof among oxidative condensates of phenylpropane units, has an antioxidant ability, and has a structure of the general formula (1). Can be used. Among the lignans having the structure of the general formula (1), the lignans represented by the general formula (2), the general formula (3) and the general formula (4) are preferable as an effect with xanthophyll.

［式中、Ｒ_１〜Ｒ_４はそれぞれ独立して水素原子、水酸基又は炭素数１〜３のアルキル基、炭素数１〜３のアルコキシル基又はＲ_１とＲ_２、Ｒ_３とＲ_４が−ＣＨ_２−Ｏ−ＣＨ_２−で結合していること、Ｒ_５とＲ_６はそれぞれ水素原子、水酸基、炭素数１〜３のアルキル基、炭素数１〜３のアルコキシル基、グルコース、ガラクトース及びフルクトースからなる群から選ばれる１種又は２種以上の糖が１〜３個グリコシド結合した前記糖鎖残基或いはＲ_７とＲ_６又はＲ_５とＲ_８は共通の酸素原子で結合していること、Ｒ_７とＲ_８はそれぞれ独立して水素原子、水酸基又は炭素数１〜３のアルキル基、炭素数１〜３のアルコキシル基、Ｒ_９とＲ_１０はそれぞれ独立して水素原子、水酸基又は炭素数１〜３のアルキル基、炭素数１〜３のアルコキシル基を示す。］

[Wherein, R _{1 to} R ₄ each independently represents a hydrogen atom, a hydroxyl group or an alkyl group having 1 to 3 carbon atoms, an alkoxyl group having 1 to 3 carbon atoms, or R ₁ and R ₂ , R ₃ and R ₄ are − Bonding with CH ₂ —O—CH ₂ —, R ₅ and R ₆ are a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxyl group having 1 to 3 carbon atoms, glucose, galactose and fructose, respectively. The sugar chain residue in which 1 to 2 or more sugars selected from the group consisting of 1 to 2 glycoside bonds, or R ₇ and R ₆ or R ₅ and R ₈ are bonded by a common oxygen atom. R ₇ and R ₈ are each independently a hydrogen atom, a hydroxyl group or an alkyl group having 1 to 3 carbon atoms, an alkoxyl group having 1 to 3 carbon atoms, and R ₉ and R ₁₀ are each independently a hydrogen atom, hydroxyl group or carbon. An alkyl group having 1 to 3 carbon atoms and 1 to 1 carbon atoms 3 represents an alkoxyl group. ]

［式中、Ｒ_１、Ｒ_２、Ｒ_３、Ｒ_４、Ｒ_５及びＲ_６は前記に同じ］

[Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are the same as above]

［式中、Ｒ_１、Ｒ_２、Ｒ_３、Ｒ_４、Ｒ_６、Ｒ_９及びＲ_１０は前記に同じ］

[Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₆ , R ₉ and R ₁₀ are the same as above]

［式中、Ｒ_１、Ｒ_２、Ｒ_３、Ｒ_４、Ｒ_９及びＲ_１０は前記に同じ］

[Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₉ and R ₁₀ are the same as above]

Examples of lignans include, for example, secoisolariciresinol, secoisolariciresinol glucoside (SDG), matailesinol, laricilesinol, isolariciresinol, nordihydroguaiaretic acid, pinoresinol, olivir, enterolactone, enterodiol , Pinodinol, P-1, sesaminol, sesamolyl and the like, for example, sesaminol (tetrahydro-1- [6-hydroxy-3,4- (methylenedioxy) phenyl] -4- [3,4] (Methylenedioxy) phenyl] -1H, 3H-furo [3,4-C] furan), P-1 (tetrahydro-1- (3-methoxy-4-hydroxyphenyl) -4- [3,4- ( Methylenedioxy) phenyl] -1H, 3H-furo [3,4-C] furan), sesamori (Tetrahydro-1- [3-methoxy-4-hydroxyphenoxy] -4- [3,4- (methylenedioxy) phenyl] -1H, 3H-furo [3,4-C] furan), pinoresinol ( And phenolic lignans such as tetrahydro-1,4-di (3-methoxy-4-hydroxyphenyl) -1H, 3H-furo [3,4-C] furan).
In particular, secoisolariciresinol and secoisolariciresinol glucoside (SDG) contained in the flaxseed extract are preferable.
Examples of the derivatives include saccharide conjugates. In addition, natural products containing these can be used, such as flaxseed extract, sesame extract, etc., and flaxseed extract (linseed lignan) is preferred because of its high lignan content.

  The mixing ratio of xanthophyll and lignan in the peripheral blood circulation improving composition of the present invention can be appropriately selected depending on the reactive oxygen species to be erased and the hydrophilicity and lipophilicity of the antioxidant, respectively, and 1: 0 in terms of free form. .01 to 100, preferably 1: 0.1 to 10. The antioxidant of this invention can be mix | blended in 0.001-99.9 weight% with respect to the whole quantity of a mixing | blending object, Preferably it is 0.01-90 weight%.

  When the peripheral blood circulation improving composition of the present invention is used, it can be used in the form of normal foods, drinks, cosmetics, and pharmaceuticals. In the following, as specific examples of xanthophyll and lignan, astaxanthin and flax lignan are described, respectively, but are not limited thereto.

  The amount of astaxanthin used in the pharmaceutical composition of the peripheral blood circulation improving composition of the present invention is an astaxanthin free form equivalent amount, and is orally administered at a dose of 0.01 to 100 mg, preferably 0.1 to 20 mg per day in adults. Or parenterally. 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 pharmaceutical product of the present invention can be contained in an amount of 0.01 to 99% by weight, preferably 0.1 to 90% by weight.

  The amount of linalignan used in the pharmaceutical composition of the peripheral blood circulation improving composition of the present invention is 0.1 to 1000 mg, preferably 1 to 100 mg, orally or parenterally per day for adults. The dosage varies depending on the age, weight, sex, degree of symptoms, and dosage form of the patient to be administered. The amount of linalignan in the pharmaceutical product of the present invention can be contained in an amount of 0.01 to 99% by weight, preferably 0.1 to 90% by weight.

  In order to assist the medicinal effect of the present invention, a substance having an assisting 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; catechins, anthocyanins, tannins, rutins, Polyphenols such as isoflavone, chlorogenic acid, ellagic acid, curcumin, coumarin (excluding lignans); linoleic acid, α- or γ-linolenic acid, arachidonic acid, eicosapentaenoic acid, succinic acid, docosahexaenoic acid and their derivatives and their salts Proteins selected from collagen, elastin, fibronectin, keratin and derivatives and hydrolysates thereof; alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, Amino acids such as histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine and their derivatives and their salts and peptides; glycolic acid, lactic acid, malic acid, citric acid, salicylic acid, etc. α-hydroxy acids and derivatives thereof 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, Sempukuka, Kaiketo, Sunpens, Sakuhakuhi, Toki, Ibukitorano, Clara, Hawthorn, Shirayuri, Hops, Neu Natural products such as La, Yokuinin, Dokudami, seaweed, natto, lemongrass, hibiscus and their extracts; adenylate derivatives such as adenosine triphosphate, adenosine diphosphate, adenosine monophosphate; iron, vanadium, molybdenum, Minerals such as manganese, copper, 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 From the group consisting of polysaccharides such as deoxyribonucleic acid and ribonucleic acid; other glycyrrhizic acid, guanine, mucin, ubiquinone, α-lipoic acid, octacosanol, allicin, alliin, and the like, and mixtures thereof It can be selected species or two or more. 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.

  Since the peripheral blood circulation improving composition of the present invention has a good peripheral blood circulation improving effect in vivo and on the skin surface, it is said that blood circulation, particularly neck / shoulder stiffness, back pain, joints, which are said to be caused by deterioration of peripheral blood circulation. It is effective for improving and preventing pain, coldness, indefinite complaints, climacteric disorder, fatigue, muscle fatigue, and eye strain. Particularly effective for neck / shoulder stiffness, low back pain, joint pain, and coldness related to muscle over-tension. Drugs, cosmetics, foods and drinks, and feeds containing the composition of the present invention can have these effects. In the effects of the present invention, the improvement effect includes not only the improvement / treatment of symptoms that have developed, but also the prevention by taking in advance in an environment or constitution that is likely to develop.

  In addition to administration of the peripheral blood circulation improving composition of the present invention, the effect of improving peripheral blood circulation can be enhanced by performing needles, wrinkles, massage, and exercise. Examples of the exercise include exercises such as bending, stretching, radio exercises, yoga, tai chi, stretching, etc., and it may be performed 2 to 4 times per week for 1 to 10 minutes per exercise.

  The pharmaceutical comprising the peripheral blood circulation improving composition of the present invention can be administered orally or parenterally. Examples of oral dosage forms include solid dosage forms such as tablets, intraoral quick disintegrating tablets, capsules, granules and fine granules, and liquid dosage forms such as syrups and suspensions. Parenteral dosage forms are administered in the form of injections, eye drops, nasal drops, patches, ointments and suppositories. A lipid-dispersed preparation is effective for increasing blood concentration. Pharmaceutical products include quasi-drugs.

  The medicine containing the peripheral blood circulation improving composition of the present invention may contain an appropriate amount of various additives used for 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. Examples of excipients include corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, and starches such as porous starch, sugars such as lactose, sucrose, and glucose, 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.

  The composition of this invention can be mix | blended and used for food-drinks and feed, and can acquire the same effect.

  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, functional health 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.

  Examples of forms of general foods, that is, foods and drinks include margarine, butter, butter sauce, cheese, fresh cream, shortening, lard, ice cream, yogurt, dairy products, sauce meat products, fish products, pickles, french fries, potato chips , Snacks, kakimochi, popcorn, sprinkles, chewing gum, chocolate, pudding, jelly, gummy candy, candy, drop, caramel, bread, castella, cake, donuts, biscuits, cookies, crackers, macaroni, pasta, ramen, buckwheat, udon , Salad oil, instant soup, dressing, eggs, mayonnaise, miso, etc., or carbonated or non-carbonated beverages such as fruit juices, soft drinks, sports beverages, non-alcohol or liquor such as tea, coffee, cocoa Yuru, it can be added to examples of the general foods such as alcoholic beverages, such as medicinal liquor.

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

  Even when the antioxidant of the present invention is blended in feed, the same effects as those of pharmaceuticals and foods and drinks can be obtained. For example, it is administered to rats, rabbits, monkeys, dogs, cats, pigs, cows, sheep, horses. be able to.

  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, one or two or more astaxanthin and lignan are added to the feed material and mixed, or one or two or more aqueous solutions of astaxanthin and lignan are sprinkled on the feed. Can do. The feed of the present invention can also be made by adding one or more astaxanthins and tocotrienols to a commercially available feed and mixing 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, casein, glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, emulsifiers such as saponin and lecithin, 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 it goes without saying that the present invention is not limited to these examples.

  Capsules were prepared according to the following formulation, and 24 men and women in each group of 33-57 years old, who were office workers, took a panel every day for 2-4 weeks.

[Sample] Soft capsules 100 mg of soft capsule skin (gelatin 75% by weight, glycerin 25% by weight) was kneaded with 200 mg of capsule contents consisting of the following components and filled to obtain 300 mg of soft capsules in a conventional manner. In addition, a compounding quantity is weight%. Astaryl oil 50F (manufactured by Fuji Chemical Industry Co., Ltd.) is an extract produced from Haematococcus alga extract oil containing 5% by weight of astaxanthin in terms of free form. Linseed lignan powder is a powder composed of linalignan (40% by weight) and cyclodextrin (60% by weight).

[Table 1] Soft capsule contents

[Example 1] Blood fluidity measurement test Blood fluidity was measured using MC-FAN (Micro Channel Array Flow Analyzer) by 6 people in each group at the start of ingestion and after completion of ingestion administration for 2 weeks.
(Blood fluidity measuring method) Blood fluidity was measured using MC-FAN. This method is a method for measuring the time required for 100 μL of blood to pass through a fine hole (6 μmφ) of a microchip. The detailed structure is shown in FIG. Blood was collected before and after ingestion to measure blood fluidity.

[Table 2] Measurement of blood fluidity by MC-FAN

  The addition of astaxanthin or flax lignan shortens the blood passage time, but the addition of astaxanthin and flax lignan further shortens the blood passage time and improves blood flow by improving blood fluidity. I was able to ask.

[Example 2] Measurement of blood flow volume At the start of ingestion and after completion of administration for 4 weeks, 6 people in each group used a laser Doppler method (Laser Doppler blood flow imaging device PeriScan PIM II manufactured by Integral) for 30 minutes. After resting, blood flow before and after ingestion at the same site in the upper right shoulder was measured.

[Table 3] Changes in blood flow

  By adding astaxanthin, flax lignan, astaxanthin or flax lignan, all of the blood flow increased, and in particular, those administered with astaxanthin and flax lignan further increased blood flow.

[Example 3] Measurement of skin surface temperature by thermography At the start of ingestion and after the end of administration for 4 weeks, 6 people in each group used a thermography Neo ThermoTVS-700 manufactured by Nippon Avionics Co., Ltd. in a temperature control room (temperature 22 ± 2 ° C). After resting for 15 minutes at a humidity of 50 ± 15 RH%), the surface temperature of the same part of the upper right shoulder was measured before and after ingestion.

[Table 4] Changes in skin surface temperature by thermography (° C)

  By adding astaxanthin, linseed lignan, astaxanthin or linseed lignan, the skin surface temperature is all increased, and in particular, those administered with astaxanthin and linalignan are further increased in skin surface temperature.

[Example 4] Measurement of muscle hardness At the start of ingestion and after the completion of administration for 4 weeks, each group of 6 people used a muscle hardness meter NEUTONE TDM-N1 manufactured by TRY-ALL for 15 minutes and rested on the upper right shoulder. Muscle hardness at the same site was measured before and after ingestion.

[Table 5] Changes in muscle hardness (tone)

  By adding astaxanthin, flax lignan, astaxanthin or flax lignan, relaxation of muscle hardness was recognized in all cases, and in particular, those administered with astaxanthin and flax lignan were further relaxed.

[Example 5] Human clinical study After administration for 4 weeks, a questionnaire was conducted on stiff shoulders and coldness.

[Table 6] Stiff shoulders

[Table 7] Coolability

  From the results shown in Tables 6 to 7, the combination of astaxanthin and linag lignan synergistically improved shoulder stiffness and chilliness compared to single administration.

[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.
Asterel powder 20F 25% by weight
Linseed lignan powder 25% by weight
Powdered cellulose 42% by weight
Reduced malt syrup 17% by weight
Agar 12% by weight
1% by weight of silicon dioxide
Sucrose fatty acid ester 3% by weight
Asteryl powder 20F (manufactured by Fuji Chemical Industry Co., Ltd.) is a powder containing 2% by weight of astaxanthin in terms of free form, and linseignnan powder is a powder containing 40% by weight of linalignan.

[Formulation Example 2] 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
Amani lignan 4g
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.

The measuring device [micro channel array flow analyzer (MC-FAN)] of erythrocyte deformability is shown. In this figure, the silicon substrate and the glass plate (both optical polishing) constituting the fine flow path are in a pressure-bonded state.

Explanation of symbols

FIG.
M Microscope GP Glass plate SS Silicon substrate D Slit height W Slit width L Channel length l Channel length

Claims (9)

A composition for improving peripheral blood circulation comprising xanthophyll and lignan. Lignan is represented by the general formula (1)

[Wherein R _{1 to} R ₄ each independently represent a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxyl group having 1 to 3 carbon atoms, or R ₁ and R ₂ , R ₃ and R ₄ are − Bonding with CH ₂ —O—CH ₂ —, R ₅ and R ₆ are a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxyl group having 1 to 3 carbon atoms, glucose, galactose and fructose, respectively. The sugar chain residue in which 1 to 2 or more sugars selected from the group consisting of 1 to 2 glycoside bonds, or R ₇ and R ₆ or R ₅ and R ₈ are bonded by a common oxygen atom. R ₇ and R ₈ are each independently a hydrogen atom, a hydroxyl group or an alkyl group having 1 to 3 carbon atoms, an alkoxyl group having 1 to 3 carbon atoms, and R ₉ and R ₁₀ are each independently a hydrogen atom, hydroxyl group or carbon. C 1-3 alkyl group, C 1-3 Represents an alkoxyl group. ]
The composition for improving peripheral blood circulation according to claim 1 represented by: Lignan is represented by the general formula (2)

[Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₆ are the same as above]
The composition for peripheral blood circulation improvement of any one of Claims 1-2 represented by these. The composition for improving peripheral blood circulation according to any one of claims 1 to 3, wherein xanthophyll is 0.01 to 100 mg and lignan is 0.1 to 1000 mg. The composition for improving peripheral blood circulation according to any one of claims 1 to 4, wherein xanthophyll is astaxanthin and lignan is flax lignan. A composition for improving peripheral blood circulation, comprising one or more of any of the following groups in the composition according to any one of claims 1 to 5;
Carotenoids (excluding xanthophyll); Vitamin B; Vitamin C; Vitamin D, Vitamin E; Tocotrienols; Glutathione and their derivatives and their salts; catechin, anthocyanin, tannin, rutin, isoflavone, Polyphenols (excluding lignans) such as 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 and their derivatives and hydrolysates; alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine Amino acids such as glucose, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine and their derivatives and salts thereof; α-hydroxy acid and derivatives thereof 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, Sempukuka, Kaiketo, Sunpens, Sakuhaku, Toki, Ibukitorano, Clara, Hawthorn, Shirayuri, Hop, Neubara, Yo Natural products such as inine, dokudami, seaweed, natto, lemongrass, hibiscus and extracts thereof; adenylate derivatives such as adenosine triphosphate, adenosine diphosphate, adenosine monophosphate; iron, vanadium, molybdenum, manganese, Minerals such as copper, 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 Polysaccharides such as deoxyribonucleic acid, ribonucleic acid, etc .; other glycyrrhizic acid, guanine, mucin, ubiquinone, α-lipoic acid, octacosanol, allicin, alliin. The composition according to any one of claims 1 to 6, which improves neck / shoulder stiffness, back pain, joint pain, coldness, indefinite complaints, menopause, fatigue, muscle fatigue, and eye strain by improving peripheral blood circulation. . The use method of a xanthophyll and lignan for manufacturing the composition for peripheral blood circulation improvement of any one of Claims 1-6 for improving the state where the blood circulation in the periphery fell. A pharmaceutical, a functional food, a health food, and a food and drink comprising the peripheral blood circulation improving composition according to any one of claims 1 to 6.

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