JP5119509B2 - Activity motivator - Google Patents

Description

The present invention relates to an activity motivation improver by enhancing basal metabolism (hereinafter sometimes simply referred to as an agent) and its use.

In order for a living organism to maintain life activity, it needs biogenic energy, which is produced in the following process. In other words, ingested food is digested, absorbed, transferred to cells, and accumulated glucose (glucose) and glycogen stored mainly in the liver and muscles through glucose 6-phosphate by glycolytic enzyme reaction, pyrubin ATP (adenosine triphosphate), NADH and NAD (nicotine) produced in a series of metabolic processes that are converted into acetyl-CoA in the mitochondria of cells and further converted into citric acid, oxaloacetate, etc. in the TCA cycle Amide adenine dinucleotide reduced and oxidized forms) are used as direct energy sources. In addition, fat undergoes a β-oxidation reaction of fatty acid, passes through acetyl CoA, is similarly metabolized in the TCA cycle, and participates in bioenergy production.

In normal mental and physical activities, aerobic glycolysis is prioritized due to the presence of sufficient oxygen, and glucose and glycogen are mainly used as bioenergy sources, and the pyruvic acid produced is sequentially released in the TCA cycle. It is metabolized and does not produce lactic acid. On the other hand, in an intense activity that requires a large amount of bioenergy (overloading work, sports exercise, etc.), anaerobic glycolysis occurs in an oxygen-deficient state, and the metabolic energy production reaction in the TCA circuit occurs. It becomes rate-determining with respect to the pyruvic acid production reaction in the previous stage, so that an excess of pyruvic acid is generated, and a part of this is converted into lactic acid by lactate dehydrogenase. Will be accumulated.

Basal metabolism is generally defined as energy consumed in a comfortable temperature (20 to 25 ° C.), both physically and mentally resting, hungry (12 to 16 hours after meals), and lying on awake state (non-patent literature). 1). In other words, basal metabolism means the minimum energy consumption necessary to maintain life, and basal metabolism measured under certain conditions has almost the same value in each individual, but physique, gender, age among individuals Varies depending on factors such as environmental conditions. For example, the larger the physique, the more the body surface area increases, and the amount of energy released from the body surface increases, so the basal metabolism increases. The girls have more body fat than the boys, and the physique is small, so the basal metabolism is usually 6-10. %Few. The basal metabolic rate per body surface area reaches its maximum at the age of 2 to 3 years, then decreases rapidly, and gradually decreases after puberty. When the environmental temperature is lowered, the amount of exothermic energy increases to maintain the body temperature, so the basal metabolism increases, and in the case of exercise or heavy work, the basal metabolism increases, and obese people have more body fat and the basal metabolism is low.

A decrease in basal metabolic rate with aging promotes obesity tendency to reduce dietary energy consumption, and lifestyle-related diseases (diabetes, hypertension, hyperlipidemia, arteriosclerosis) that have been suggested to have a causal relationship with obesity Symptom, ischemic heart disease, etc.). In addition, since the amount of energy produced in the body is reduced, it causes a delay in fatigue recovery and fatigue of the body, and has a negative impact on psychological and psychological aspects such as motivation and motivation.

Lactic acid has traditionally been considered to be a muscle fatigue substance along with ammonia production and scorching glucose during physical activity, and has been considered to be a major factor in muscle pain caused by fatigue. However, lactic acid is converted to acetyl-CoA. Although it may be interpreted as a substance that relieves fatigue rather than being metabolized by entering into the TCA circuit (Non-patent document 2), lactic acid generally accumulates in muscles as fatigue occurs. The reason for interpreting lactic acid as one of fatigue-related substances is that the acidity of muscle tissue increases, the activity of enzymes decreases, and the production of bioenergy necessary for muscle exercise is suppressed. Is influential.

In order to alleviate fatigue, daily intake of carbohydrates and B vitamins, which are bioenergy sources in the diet, is recommended to compensate for the lack of energy, and nutritional balance can be achieved as an easy way to relieve fatigue. Taking a fresh meal, taking a bath and massage to improve blood circulation, and taking sufficient rest. In addition, from the viewpoint of fatigue prevention and recovery, physical strength enhancement, a specific amino acid mixture (Patent Document 1), beef-degrading peptide (Patent Document 2), a combination of mineral yeast, dolomite, heme iron and seaweed (Patent Document 3), Ingestion of a reishi component (Patent Document 4), coenzyme Q10, a combination of carnitine and an organic acid (Patent Document 5), milk whey protein (Patent Document 6) and the like has been proposed. However, when these are taken orally, there are some disadvantages in terms of digestion and absorption, and there are few that are sufficiently satisfactory in practical use.

By the way, the following things are known about the thioctic acid mentioned later. Thioctic acid is α-lipoic acid, 1,2-diethylene-3-pentanoic acid, 1,2-diethylene-3-valeric acid, 1,2-dithiolane-6-pentanoic acid or 1,2-dithiacyclopentane. It is also called -3-valeric acid. Pale yellow to yellow crystal or crystalline powder with specific odor, melting point: racemic: 60-61 ° C, R: 46-48 ° C, S: 45-48 ° C, slightly in water Dissolves and dissolves in organic solvents such as ethanol and acetone and dilute alkaline water. Thioctic acid is synthesized in vivo by plants, animals / humans, and microorganisms, and is bioavailable as one of various coenzymes such as pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex, and catalyzes acyl transfer reaction. It is known to do.

In recent years, research on the function of thioctic acid and its reduced form dihydrothioctic acid (6,8-dimercapto-octanoic acid) has progressed, and these have attracted attention as having strong antioxidant power, superoxide radicals, It reacts easily with reactive oxygen species such as hydroxy radical, peroxy radical, singlet oxygen, etc., easily reacting to lose the action of the active oxygen species, reducing damage to living tissues, and interacting with vitamin C and glutathione. It is said that it has the effect of protecting cell membranes by action and regenerating vitamin E (Non-patent Document 2). The pharmacological action of thioctic acid has been reported to be effective for pathological models of oxidative stress such as tissue damage during ischemic reperfusion, diabetes, cataracts, neurodegeneration, radiation damage, inflammatory diseases, etc. ( Non-patent document 3). However, there are no reports on thioctic acid and its derivatives that enhance basal metabolism, thereby preventing or early recovery from fatigue, or improving willingness to act.

In general, the technology of coating powders and particles as a core substance and surrounding the surface with a hydrophobic substance such as a polymer substance or lipid has been known, and the coating process stabilizes the taste and aroma of the core substance. It is proposed to prevent the leakage of the component when the core substance is a water-soluble component, or to prevent moisture absorption, to prevent powder absorption, or when the core substance is a water-soluble component (Patent Document 7, 8 and 9). However, the protective action of the core substance by such coating treatment is aimed at improving the physical properties such as quality maintenance of flavor components, moisture resistance, prevention of leakage of water-soluble components,

JP-A-8-198748 JP-A-10-113147 Japanese Patent Laid-Open No. 2003-198 JP-A-5-124974 JP-A-2005-97161 Japanese Patent Laid-Open No. 2005-289861 JP 63-226250 A JP-A-9-70285 Japanese Patent No. 3512238 Nutrition Handbook Editorial Committee, “Third Edition Nutrition Handbook”, Gihodo Publishing Co., Ltd., issued in November 1996 Thomas H.M. Pedersen et al., “Intracellular Acidity enhancement the Working Mus.” (USA), 2004, Science, 305, August 20, pp. 1144-147. Indani Maitra et al., “Α-lipoic acid presents basicion sulfoximine-induced catalyst formation in newborn rats.”, P. 24, 1995, Free Radical Biolog.

In view of the present situation, the present inventors have enhanced the basic metabolism of the body, and based on this, for the prevention or early recovery of fatigue, the improvement of willingness to act, the prevention or improvement of obesity, and further the prevention of lifestyle-related diseases It was an object to develop a useful material or composition and to provide a composition in an aspect that can be effectively used industrially.

In order to solve the above problems, the present inventors have conducted extensive studies on the relationship between various raw materials and basal metabolism enhancing ability, fatigue, motivation for activity, obesity, various diseases, etc. The inventors have found that the present invention has extremely remarkable effects and that it can be effectively used in the fields of foods and drinks, feeds, cosmetics, pharmaceuticals, etc., and has completed the present invention.

That is, according to the present invention is characterized by containing thioctic acid as an active ingredient, activity motivation agent is provided by basal metabolism enhancement.

In this agent , the thioctic acid is selected from the group consisting of thioctic acid, dihydrothioctic acid which is a reduced form thereof, optical isomers thereof, salts, esters and amides of the respective substances, and cyclodextrin inclusion products thereof. It is desirable that it is one type or two or more types.

Further, the thioctic acid is selected from the group consisting of thioctic acid, dihydrothioctic acid which is a reduced form thereof, optical isomers thereof, salts, esters and amides of the respective substances, and cyclodextrin inclusions thereof. More preferably, the outer surface of seeds or two or more crystals, powders and / or particles is coated with lipids. Further, the thioctic acid is one kind selected from the group consisting of thioctic acid, dihydrothioctic acid which is a reduced form thereof, optical isomers thereof, salts, esters and amides of the respective substances, and cyclodextrin inclusion products thereof. Alternatively, it is more preferable that the outer surface of two or more kinds of crystals, powders and / or particles is coated with lipids and the outer surface is further coated with a hydrophilic substance. The thioctic acids are preferably racemic in optical isomers.

According to the present invention, the thioctic acid, caffeine, creatine and derivatives thereof, glucosamine, chondroitin, chondroitin sulfate, collagen hydrolyzate, choline, phosphatidylcholine, choline salt, serine, phosphatidylserine, methylsulfonylmethane, whey Protein, pyruvic acid and its salt, L-carnitine, its precursor lysine or methionine and their salt, D-ribose, amino acid, branched chain amino acid, taurine, coenzyme Q10, vitamin B1, vitamin B2, nicotinic acid, pantothene The aforementioned agent is provided in combination with at least one selected from the group consisting of acid, lactoferrin, conjugated linoleic acid, citric acid, malic acid, mineral yeast, ginger, pepper, and hydroxycitric acid.

In this agent , the raw material components used in combination are creatine and / or a derivative thereof, L-carnitine and / or a precursor thereof, lysine or methionine and / or a salt thereof, coenzyme Q10, vitamin B1, vitamin B2, phosphatidylserine, ginger One or more selected from the group consisting of red pepper and hydroxycitric acid is more preferable, and creatine and / or a derivative thereof is most preferable. As the creatine derivative, it is preferable to use one or more selected from the group consisting of creatine salt, creatine monohydrate, creatine citrate, creatine pyruvate and phosphocreatine.

In the present invention, enhancement of basal metabolism includes at least one of the group consisting of prevention or early recovery of fatigue, improvement of motivation for activity, prevention or improvement of obesity, and prevention of lifestyle-related diseases. Therefore, the agent should be construed as an agent for preventing or early recovery from fatigue by enhancing basal metabolism, improving motivation for activity, preventing or improving obesity, or preventing lifestyle-related diseases.

According to the present invention, further comprising prevention of or early recovery of fatigue due to enhancement of basal metabolism, improvement of willingness to act, prevention or improvement of obesity, or lifestyle-related diseases, characterized by comprising any one of the above-mentioned agents Food and drink for prevention is provided. Furthermore, any of the above-mentioned agents or foods and drinks are taken orally before exercise, preventing or early recovery of fatigue by enhancing basic metabolism, improvement of motivation for activity, prevention or improvement of obesity, or lifestyle-related diseases A method for prevention is provided.

The agent of the present invention has excellent quality stability, and when taken orally, the active ingredient is efficiently absorbed without being digested and decomposed in the body, and has a remarkable effect on the enhancement of basal metabolic rate. It is extremely effective for the prevention and / or early recovery of fatigue associated with the enhancement of basal metabolism, especially for preventing fatigue, and by increasing the basal metabolism, it is effective for improving psychological and psychological aspects such as motivation, motivation and vitality. It is also useful for the prevention and improvement of obesity and the prevention of various lifestyle-related diseases associated with obesity. For this reason, the agent of the present invention can be effectively used in the fields of foods and drinks, feeds, pharmaceuticals and the like as the basal metabolism-improving agent or in the form contained in the conventional products of the various fields.

The present invention is described in detail below. A first aspect of the agent according to the present invention is characterized by containing thioctic acids as active ingredients.

Here, the origin and type of thioctic acids are not particularly limited, and natural product extracts of organs such as livers of cattle and pigs, and chemical synthetic products starting from ethylene and adipic acid esters are known. It may be collected and manufactured by the method described above. In addition, since thioctic acid has an asymmetric carbon, optically enantiomers ((R) -enantiomer and (S) -enantiomer) exist, but any one of these thioctic acids according to the present invention can be used in any proportion. Or a racemic mixture or a racemate. In the industrial production level, it is easy to use a commercially available racemate that is inexpensive and easily available, and it is desirable to use the racemate because the desired effect of the present invention is more strongly expressed.

As the thioctic acid used in the basal metabolism improving agent according to the present invention, various derivatives in addition to the thioctic acid can be appropriately used. Among them, one or two kinds selected from the group consisting of reduced forms of thioctic acid, optical isomers thereof, preferably racemates, salts, esters and amides of the respective substances, and cyclodextrin inclusions thereof. The above is desirable. Specific examples of the reduced form of thioctic acid include dihydrothioctic acid, dihydrolipoic acid, 6,8-dimercapto-octanoic acid and the like. Similarly, optical isomers include (R) -thioctic acid and (S) -thiocto (R), (S) -thioctic acid, (R) -dihydrothioctic acid, (S) -dihydrothioctic acid, (R), (S) -dihydrothioctic acid, etc. (R) , (S) -thioctic acid, (R), (S) -dihydrothioctic acid, and the like, (R) -thioctic acid, (S) -thioctic acid, (R), (S) -thioctic acid, ( Potassium salts such as R) -dihydrothioctic acid, (S) -dihydrothioctic acid, (R), (S) -dihydrothioctic acid, sodium salts, calcium salts, magnesium salts, etc., and (R) -thioctic acid as an ester , (S) Thioctic acid, (R), (S) -thioctic acid, (R) -dihydrothioctic acid, (S) -dihydrothioctic acid, (R), (S) -dihydrothioctic acid and the like and polyhydric alcohols (ethylene glycol, Partial ester or complete ester or glycerides (monoglyceride, diglyceride, triglyceride) with propylene glycol, butanediol, neopentyl glycol, glycerin, erythritol, polyglycerin or the like, or higher alcohols having 10 to 22 carbon atoms Monoesters with (decanol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, etc.), amides as (R) -thioctic acid, (S) -thioctic acid, (R) (S) - thioctic acid, (R) - Dihydrothiazol octoate, (S) - Dihydrothiazol octoate, (R), (S) - can be exemplified amides such dihydrothiazoles octoate. Examples of cyclodextrin inclusions include inclusions of the thioctic acids with α-, β-, γ- and / or δ-cyclodextrin. In the present invention, α- or γ-cyclo Dextrin inclusions are preferred. In addition, this invention is not limited by these illustrations.

Thioctic acids that can be used in the basal metabolism improving agent according to the present invention include those obtained by coating the outer surface of one or more crystals, powders and / or particles of the thioctic acids with lipids, This embodiment suppresses thermal alteration (decomposition, polymerization, discoloration, etc.), moisture absorption or oxidative modification of thioctic acids, improves flavor and taste, and also from the point of slow release of active ingredients after ingestion, etc. More desirable.

The lipids that coat the outer surface of the thioctic acid crystals, powder, and / or particles may be acceptable in the industrial field where the basal metabolism-improving agent of the present invention is used. Industrial fats and oils, fatty acid glycerides, fatty acids, fatty acid esters, fatty acid amides, higher alcohols, waxes, sterols, glycolipids, phospholipids and the like can be used alone or in combination. Of these, lipids having a melting point of about 30 ° C. or higher are preferable in consideration of coating workability and physical properties of the coating (stability, solidification, fluidity, meltability, solubility, etc.). More preferred forms are lipids having a melting point of about 40 ° C. to about 70 ° C., and most preferred forms are lipids having a melting point of about 40 ° C. to about 60 ° C. When the melting point is less than about 30 ° C., the coating may not be able to maintain a solid state during use, and may form a lump or impair flowability. On the other hand, when the temperature exceeds about 70 ° C., the thioctic acids themselves may be deteriorated due to the influence of heat treatment and mechanical energy when producing the composition according to the present invention.

Specific examples of such lipids include soybean oil, rapeseed oil, corn oil, sunflower oil, cottonseed oil, wheat germ oil, rice oil, sesame oil, olive oil, safflower oil, palm oil, palm kernel oil, coconut oil, linseed oil , Vegetable oils such as peanut oil, animal fats such as beef tallow, lard, fish oil, processed oils and fats that have been subjected to one or more of such treatments as fractionation, transesterification, decolorization, deodorization, etc., partially or completely Various hydrogenated hydrogenated oils, saturated fatty acids having 2 to 22 carbon atoms (acetic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, stearic acid, 12-hydroxystearic acid , Isostearic acid, arachidic acid, behenic acid, etc.) or unsaturated fatty acids (palmitoleic acid, oleic acid, elaidic acid, linoleic acid, α-linolenic acid) , Γ-linolenic acid, ricinoleic acid, arachidonic acid, icosapentaenoic acid (EPA), erucic acid, docosahexaenoic acid (DHA), etc., salts of these arbitrary fatty acids (sodium salt, potassium salt, calcium salt, magnesium salt, etc.) Partial or complete with esters with monohydric alcohols (methanol, ethanol, propanol, butanol, etc.), polyhydric alcohols (monomers or polymers such as ethylene glycol, propylene glycol, butanediol, neopentyl glycol, glycerin, erythritol, etc.) Esters or glycerides (monoglyceride, diglyceride, triglyceride), higher alcohols having 10 to 22 carbon atoms (decanol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol, Sostearyl alcohol, behenyl alcohol, etc.), waxes (carnauba wax, rice wax (rice bran wax), candelilla wax and other plant-derived waxes, beeswax, whale wax, shellac wax and other animal-derived waxes, paraffin wax, microcrystalline wax, etc. Oil-derived wax, wax derived from minerals such as montan wax, ozokerite, polyethylene wax, synthetic waxes such as esters of the above fatty acids and higher alcohols, sterols (animal cholesterol, plant campesterol, stigma) Ergosterols derived from fungi such as sterol and sitosterol, and derivatives thereof, phospholipids (lecithin derived from animals and plants, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinos , Phosphatidylserine, phosphatidic acid, sphingomyelin, etc.), glycolipids (monoglucosyl diglyceride, monogalactosyl diglyceride, diglucosyl monoglyceride, digalactosyl monoglyceride, monoglucosyl diglyceride, digalactosyl diglyceride, sucrose fatty acid ester, etc.) be able to. In addition, this invention is not limited at all by these illustrations.

In the present invention, any one or a mixture of two or more of the above-mentioned various lipids can be used. Suitable types of lipids include the above edible oils or industrial fats, fatty acid glycerides, fatty acid esters and Waxes, more preferably edible fats and oils and fatty acid glycerides, and these and one or more selected from fatty acids, higher alcohols, sterols, glycolipids or phospholipids The combination is a more desirable embodiment from the viewpoint of adjusting the melting point of the coated lipid, reinforcing the coating film, and the like.

A known method can be used to coat the outer surface of the thioctic acid crystals, powder and / or particles with lipids. That is, ball mill, flash blender (powder granule mixer), V-type mixer, high-speed mixer, high-speed paddle mixer, heat-melt mixer, ultrasonic super-humidified liquid-type mixer, tumbler mixer, pressure extruder, etc. The thioctic acid crystals, powder and / or particles and the heated and melted lipids are uniformly mixed, cooled and solidified, and then pulverized. A method of coating by spraying or dripping the lipids which have been formed, and stirring and mixing the thioctic acids of the above-mentioned form and particulate lipids at high speed, and bringing them into contact or colliding with each other, thereby producing crystals, powders and / or thioctic acids. Alternatively, a method in which particulate lipids are uniformly attached to the entire surface of the particle and coated is possible. In the present invention, among these, thioctic acid crystals, powders and / or particles and particulate lipids having a specific melting point or higher are mixed with high-speed stirring, and both are brought into contact with or collided with each other to obtain the thioctic acid of the above form. A method of uniformly coating particulate lipids on the entire surface of acids is desirable.

In the above-described coating treatment, the ratio of thioctic acid crystals, powders and / or particles to lipids, thioctic acid crystals, powder and particle shapes and sizes, lipid types and melting points, coating film thickness and Although it is difficult to define uniformly depending on factors such as properties, about 0.05 parts by weight to about 10 parts by weight, preferably about 0 parts by weight of lipids are generally added to 1 part by weight of crystals, powders and / or particles of thioctic acids. .1 part by weight to about 5 parts by weight. If the lipids are less than about 0.05 parts by weight, the coating state is not sufficient and it is difficult to achieve the desired effect. Conversely, if the lipids exceed about 10 parts by weight, the thioctic acid content in the coating is low, In the scene where it is used, the blending rate and the like are limited, and the practical value may be impaired.

The above-described coating of thioctic acids with lipids is more desirable in that the outer surface is further coated with a hydrophilic substance, including the case where it is applied to an aqueous composition such as a beverage. . Here, the hydrophilic substance means a substance that further coats the outer surface of the coating with lipids and has a coating film-forming ability having an affinity with an aqueous substance. Specific examples include polysaccharides (xanthan gum, guar gum, Tamarind seed gum, psyllium seed gum), starch and modified starch, yeast cell wall components, glucan, mannan, shellac, sodium alginate, gelatin, carrageenan, pullulan, carboxymethylcellulose, soybean protein, whey protein, zein, etc. Can do. More preferably, it is one or more selected from the group consisting of polysaccharides, starch, yeast cell wall components, shellac, gelatin, soybean protein, zein and mannan, and more preferably yeast cell wall components, shellac and gelatin. is there.

In order to coat such a hydrophilic substance, a method according to the above-described method for coating lipids may be employed. That is, the hydrophilic substance is appropriately dissolved in water, ethanol, or other solvent to form a liquid, and this is attached to the outer surface of thioctic acid previously coated with lipids and dried to coat the hydrophilic substance. A film can be formed. The coating thus obtained becomes a double-coated structure having a hydrophilic substance as the outermost layer. When this is used for foods, drinks, feeds, cosmetics, pharmaceuticals, etc., the affinity with aqueous raw materials and ingredients is increased, It becomes easy to prepare a homogeneous composition of thioctic acids with low water solubility.

In the above-described coating of thioctic acids with lipids and the double coating in which the coating is further coated with a hydrophilic substance, these include Garcinia camphor peel, red pepper rhizome, guava leaf and extracts thereof (water And / or one or two selected from the group consisting of an extract with a hydrophilic organic solvent (e.g., a lower monohydric alcohol such as ethanol, acetone, its fraction, a solvent fraction or a purified product), and carnitine. More preferably, the presence of red pepper rhizome extract and / or carnitine, and most preferably carnitine, allows further suppression of thermal and / or oxidative denaturation and degradation of thioctic acids and contains thioctic acids with excellent stability. Such a thioctic acid is more desirable since a coating is obtained.

In order to allow these combined raw materials to coexist in the aforementioned thioctic acid-containing coating, (i) the combined raw material is mixed with a coating in which lipids are coated on thioctic acid crystals, powder and / or particles, (ii) ) A lipid is coated on a mixture of the thioctic acid crystals, powders and / or particles and the combination raw material. (Iii) A part of the combination raw material is dispersed in the thioctic acid crystals, powder and / or particles. Or (iv) a solution obtained by coating the lipids on the thioctic acid crystals, powder and / or particles, and a solution, dispersion or emulsification containing the combined raw material and the hydrophilic substance. Any of attaching and drying and coating the liquid is possible, and a combination of these embodiments may be used. In the present invention, the aspects (i) and (iv) have the desired effects of the present invention, the production is simple, and the handling workability of the coating is good, but the aspects (ii) and (iii) are desirable. It is easy to express the effect more powerfully.

In such an embodiment, the mixing ratio of the coating material obtained by coating the crystals, powders and / or particles of thioctic acid with lipids or lipids and a hydrophilic substance and the coexisting raw material is the coexistence with respect to 1 part by weight of the coating material. The raw material is about 0.01 parts by weight to about 10 parts by weight, more preferably about 0.1 parts by weight to about 1 part by weight. When the amount is less than about 0.01 parts by weight, the desired effect cannot be improved by mixing the coexisting raw materials. When the amount exceeds about 10 parts by weight, the content of thioctic acid in the coating and further in the agent using the coating is further exceeded. As a result, the thioctic acid content in various products containing the thioctic acid-containing agent is limited, and the desired effect of thioctic acid itself cannot be expected in the product stage.

A second aspect of the agent according to the present invention is the above-mentioned thioctic acid, that is, thioctic acid, dihydrothioctic acid, optical isomers thereof (preferably racemate), salts, esters and amides of the respective substances, and these 1 type or 2 types or more selected from the group consisting of cyclodextrin inclusions of the above, lipid coatings obtained by coating the outer surface of these crystals, powders and / or particles with lipids, or the lipids Single or plural double coatings in which the outer surface of the coating is further coated with a hydrophilic substance, caffeine, creatine and derivatives thereof, glucosamine, chondroitin, chondroitin sulfate, collagen hydrolyzate, choline, choline salt, phosphatidylcholine, Serine, phosphatidylserine, methylsulfonylmethane, whey protein, pyruvic acid and its salts, L-carnichi Lysine or methionine which is a precursor thereof and salts thereof, D-ribose, amino acid, branched chain amino acid, taurine, coenzyme Q10, vitamin B1, vitamin B2, nicotinic acid, pantothenic acid, lactoferrin, conjugated linoleic acid, citric acid, It is a basal metabolism enhancer comprising at least one selected from the group consisting of malic acid, mineral yeast, ginger, red pepper, and hydroxycitric acid.

In the present invention, among such combined raw material components, creatine and / or a derivative thereof, L-carnitine and / or a precursor thereof, lysine or methionine and / or a salt thereof, coenzyme Q10, vitamin B1, vitamin B2, phosphatidylserine One or two selected from the group consisting of ginger, pepper, and hydroxycitric acid is more desirable, and creatine and / or its derivatives are most desirable. Here, as the creatine derivative, it is preferable to use one or more selected from the group consisting of creatine salt, creatine-hydrate, creatine citrate, creatine pyruvate and phosphocreatine.

As described above, the second aspect of the agent according to the present invention contains thioctic acids and at least one of the combined raw material components, and the ratio of the thioctic acids and the combined raw material components in this case is as follows: However, although it is difficult to uniformly define by these types and forms, thioctic acids: combined raw material components = 90 to 10:10 to 90 (weight ratio) is preferable, and 70 to 50:30 to 50 is more preferable.

The agent according to the present invention can itself be used as various products in food and drink, pharmaceuticals, cosmetics, feed, and other industrial fields, or can be used in an embodiment in which it is used as a part of blended raw materials of the various products. In particular, food and drink applications are suitable. Examples of these are described below, but the present invention is not limited thereby.

Specific examples of food and drink to which the agent according to the present invention can be applied include beverages such as vegetable juice, fruit juice drinks, soft drinks, tea, soups, jelly, pudding, yogurt, cake premix products, confectionery, sprinkles , Miso, soy sauce, sauce, dressing, mayonnaise, vegetable cream, miso, seasonings such as grilled meat sauce and noodle soup, noodles, udon, soba noodles, spaghetti, processed meat and fish products such as ham and sausage, hamburg, croquette Various processed foods such as sprinkles, boiled rice cakes, jam, milk, cream, butter, spread and cheese, powdered, solid or liquid dairy products, margarine, bread, cakes, cookies, chocolate, candy, gummi, gum, etc. Powder, granule, pill, tablet, soft capsule, hard capsule, paste or liquid Nutrient supplements, food for specified health use, functional foods, mention may be made of health food products, the concentrated liquid diet and dysphagia for food diet and the like.

In order to produce these foods and drinks, a known raw material and the agent according to the present invention may be used, or a part of the known raw material may be replaced with the agent of the present invention and produced by a known method. For example, the agent according to the present invention and, if necessary, glucose (dextrose), dextrin, lactose, starch or processed product thereof, excipients such as cellulose powder, vitamins, minerals, fats and oils of animals and plants and seafood, protein ( Animal, plant and yeast-derived proteins, hydrolysates thereof, etc.), carbohydrates, pigments, fragrances, antioxidants, other edible additives, powders containing various nutritional functional ingredients, and edible ingredients such as extracts, mixed into powder , Processed into the shape of granules, pellets, tablets, etc., processed into the general foods of the above examples by conventional methods, or coated with gelatin, sodium alginate, carboxymethylcellulose, etc. to form a capsule Or processed into a beverage (drinks) form and used as a dietary supplement or health food. In particular, tablets, capsules and drinks are desirable.

The ratio in the case of blending the agent according to the present invention into food and drink is the form of the food and drink, the type and content of thioctic acids and concomitant raw material components in the agent according to the present invention, the types and ingredients of other blended raw materials, etc. Although it is difficult to define uniformly because of the difference, the thioctoic acid content in the food and drink is about 0.01 wt% to about 90 wt%, more preferably about 1 wt% to about 50 wt%. Acids, lipid coatings and double coatings thereof, and further coexisting materials appropriately selected from garcinia camphor peel, red pepper rhizome, guava leaves, extracts thereof, carnitine and the like, creatine and / or derivatives thereof, L- Carnitine, its precursor lysine or methionine and / or their salts, coenzyme Q10, vitamin B1, vitamin B2, phosphatidylserine, ginger, pepper, and chick The combined ingredients are suitably selected from Rokishikuen acid, and the formulation designed appropriately combining other food or beverage raw material for production, the present invention according to a conventional method may be prepared food products of interest. In foods and beverages with a thioctic acid content of less than about 0.01% by weight, in order to expect the desired effect of thioctic acids, a large amount of the foods and beverages must be ingested. From the practical aspect of the considered food or drink, the most thioctic acid content in the food or drink according to the present invention is about 95% by weight. The food / beverage product according to the present invention is about 10 mg to about 1000 mg, preferably about 30 mg to about 500 mg, more preferably about 50 mg to about 200 mg per day, for example, in the case of humans. It can be taken into the body by a method such as tube administration.

The agent and food / drink according to the present invention are desirably taken orally prior to various activities such as sports, heavy labor, and physical exercise in accordance with the object of the present invention. One of the body basal metabolisms is increased, and especially with the enhancement of the basal metabolism, a remarkable effect is recognized in prevention of fatigue and early recovery. From this point of view, in the present invention, there is no restriction that the combination raw material components such as thioctic acids, thioctic acids, and creatine are included in the same composition, and they are prepared as a plurality of compositions or foods and drinks separately containing them. However, it is within the technical scope of the present invention to ingest such a composition or food or drink almost simultaneously. In addition, the agents and foods and drinks according to the present invention, when taken in daily life, regardless of the above-mentioned exercise, etc., are recognized to promote psychological and psychological aspects such as activity motivation and vitality based on the basal metabolic enhancement effect, It is also effective in preventing or improving obesity and preventing lifestyle-related diseases caused by obesity.

Next, although an Example is given and this invention is demonstrated in detail, this invention is not limited by this. In each example,%, part and ratio are all on a weight basis.

(Production Example 1)
(1) Thioctic acid lipid coating Crystal powder of thioctic acid (manufactured by Degussa, Germany, trade name: ALIPURE (registered trademark), racemic body) heat-melted rapeseed oil (manufactured by Kawaken Fine Chemical Co., Ltd.) (Melting point: 67 ° C., flake shape) 200 g was added, mixed well and dispersed uniformly, and then cooled and solidified to room temperature. Next, the solidified product was pulverized with a high-speed mixer, and sieved with 100 mesh (Tyler mesh; the same applies hereinafter) to obtain a thioctic acid lipid coating (sample 1) having a particle size of 150 μm or less.

200 g of thioctic acid and 200 g of creatine monohydrate (manufactured by Degussa, Germany, trade name: CREAPURE (registered trademark)) and powdered rapeseed oil (manufactured by Kawaken Fine Chemical Co., Ltd., melting point: 60 ° C., average particle size) 200g) was charged into a fine particle coating granulator (Powrec Co., Ltd., model: MP-25SFP), stirred and mixed with a fan blade rotating at 1000 rpm for 30 minutes, and both raw materials were brought into contact and collided. Thus, a thioctic acid lipid coating (sample 2) having an average particle diameter of about 100 μm was obtained.

In the production example of the thioctic acid lipid coating (sample 2), 200 g of thioctic acid and 200 g of creatine were mixed with 150 g of thioctic acid and 50 g of guava leaf extract (product name: guava leaf extract powder-S). A treatment was performed in the same manner except that the thioctic acid lipid coating (Sample 3) was obtained.

In the production example of the thioctic acid lipid coating (sample 2), 200 g of thioctic acid was charged into a coating granulator and stirred and flowed, soybean oil: 40 parts, carnauba wax: 40 parts and soy sterol: 20 parts Lipid mixture 100 g, L-carnitine-L-tartrate (manufactured by Lonza Japan Co., Ltd.) and creatine (same as sample 2), and sucrose behenate (Mitsubishi Chemical Foods Co., Ltd., Ryoto) (Registered trademark) Sugar ester, HLB: 1-2) 20 g of a homogeneous liquid material heated, melted and mixed at 70 ° C. is sprayed from the spray nozzle to coat the thioctic acid surface, and the thioctic acid lipid coating (sample 4) Got.

(Production Example 2)
(2) Double coating of thioctic acid Coating granulation using a part of any of the above thioctic acid lipid coatings (sample 1, sample 3) in the production example of the thioctic acid lipid coating (sample 2) A dispersion (made by Kirin Brewery Co., Ltd., trade name: East Wrap (registered trademark)) containing 8.0% yeast cell wall is charged into an apparatus (provided by the company, model: MP-01SFP), and stirred and flowed. It sprayed and the surface of each thioctic acid lipid coating particle was coat | covered with the hydrophilic material, and the thioctic acid double coating (sample 5, sample 7) was obtained. In addition, the thioctic acid lipid coating (sample 2 and sample 4) was treated in the same manner except that the dispersion containing 8.0% yeast cell wall was replaced with an aqueous ethanol solution containing 20% shellac. Coatings (Sample 6, Sample 8) were obtained.

(Test Example 1)
The effects of the composition according to the present invention on basal metabolism, fatigue and the like were examined by the method described below. That is, the test substances are thioctic acid, thioctic acid lipid coating (Sample 1 and Sample 3 in Production Example 1), and thioctic acid double coating (Sample 5 and Sample in Production Example 2). 7), a mixture of thioctic acid and creatine (1: 1), a lipid coating of a mixture of thioctic acid and creatine (Sample 2 and Sample 4 of Preparation Example 1), a double coating of a mixture of thioctic acid and creatine (Production) Sample 6 and sample 8) of Example 2 were used, and the comparative test substance was creatine. Here, thioctic acid was manufactured by Degussa, Germany, trade name: ALIPURE (registered trademark), creatine was manufactured by Degussa, Germany, trade name: CREAPURE (registered trademark), and creatine monohydrate.

4-week-old male Wistar rats (average body weight: 110 g) were preliminarily raised for 1 week, and 20 rats per group were used as a control group, a test substance administration group (10 animals for each test substance), and a comparative test substance administration group. divided. Rats in each group were given the standard diet (AIN-76A) shown in Table 1 twice a day at a predetermined time, physiological saline was given to the subject group, and the test substance administration group and the comparative test substance administration group were tested. An aqueous solution in which a substance (100 mg / kg body weight as a thioctic acid dose) or a comparative test substance (200 mg / kg body weight as a creatine dose) is dissolved or dispersed in physiological saline is orally administered once a day and maintained for 3 weeks. did. During this period, in order to get used to the swimming exercise of the load swimming exercise test described later, the animal was allowed to swim freely for 30 minutes every day without applying a load.

Three weeks after the test breeding, the resting oxygen consumption and carbon dioxide excretion were measured, and a known method (JA Weststate, Am. J. Clin. Nutr., 1993, 58, 592). To the metabolic rate calculation formula described on page 601), the basal metabolic rate per rat body weight was determined by the following calculation formula. That is, basal metabolic rate (kJ / kg / min) = 4.184 × [{4.686 + 1.096 × (respiration quotient−0.707)} × VO2]. Here, respiratory quotient = (carbon dioxide excretion per unit time) / (oxygen consumption per unit time), and VO2 means the amount of oxygen (mL) consumed by rat per minute (kg). VO2 (mL / kg / min) = {(oxygen concentration in the atmosphere at the time of measurement−oxygen concentration in the exhalation gas) / 100} × (expiration volume for 15 minutes (mL)) × (1000 / rat body weight ( g)) × (1/15 (min)). The results are shown in Table 2. In addition, after breeding under the above conditions, a weight corresponding to 4% of the body weight was attached to the body of each rat, and a swimming exercise was forcibly carried out for 1 hour in a water tank, blood was collected after the swimming exercise, and blood lactic acid level was measured. The results are shown in Table 3.

From Table 2, it can be seen that the basal metabolic rate is significantly increased in the test substance administration group as compared with the control group, and in the test substance administration group, when the thioctic acid according to the present invention is administered, the basis is higher than in the case of creatine alone administration. A synergistic effect was observed when thioctic acids and creatine were used in combination with a high ability to enhance metabolism. Also, from Table 3, blood lactate level due to swimming exercise load is markedly increased in the control group, but low in the thioctic acid group, especially in the thioctic acid and creatine combination group. It was. Therefore, thioctic acids have the effect of preventing fatigue by enhancing the basal metabolic rate and suppressing the production of lactic acid, which is considered as one of the fatigue substances, and the combined use of thioctic acids and creatine is It was judged to have an effect of synergistically exerting an effect of enhancing basal metabolism and an effect of suppressing lactic acid production after exercise.

The test breeding described above was continued for another week under the same conditions, and after the total period of the test breeding was 4 weeks, half of the rats in each group (n = 10) were sacrificed, and body weight, blood components (blood glucose level, free fatty acid) Content, neutral fat content and cholesterol content), adipose tissue weight, lactic acid content and glycogen content in muscle, respectively. A part of the result is shown in Table 4.

From Table 4, oral administration of thioctic acid significantly suppresses body weight gain and reduces the weight of abdominal adipose tissue, and these tendencies become synergistically significant when thioctic acid and creatine are administered in combination. It became clear. Therefore, it can be interpreted that oral ingestion of thioctic acids, thioctic acids and creatine is particularly effective for preventing obesity as well as suppressing the accumulation of visceral fat. In addition, administration of thioctic acids and administration of thioctic acids and creatine together revealed that both blood glucose level and blood lipid content are reduced, which is to prevent so-called lifestyle-related diseases such as diabetes and hyperlipidemia. Useful in connection. Further, it has been clarified that the combined use of thioctic acids, thioctic acids and creatine increases the amount of glycogen in muscle, and considering that glycogen is used as an immediate energy source during momentary anoxic exercise, the present invention Such agents are considered useful for enhancing the motor function of the body, preventing fatigue and early recovery.

Next, with respect to the remaining half (n = 10) of the rats in each group after the total period of the breeding of the test described above for 4 weeks, a weight corresponding to 4% of the body weight is attached to the body of each rat and the water is forcedly applied in a water tank. Immediately after swimming for 1 hour, the animal was sacrificed and the lactic acid content in the muscle was measured. The results are shown in Table 5. From the data in Table 5, the lactic acid content in the cypress muscle is significantly increased by the swimming exercise load (control group), but this increase is remarkably reduced in the thioctic acid administration group and the thioctic acid and creatine combination administration group. It was revealed. Since lactic acid is a fatigue substance produced with exercise, the test substance according to the present invention is considered to be effective for recovery from fatigue.

(Test Example 2)
Ten volunteer female adults (21-54 years old, average age: 32.3 years old) were filled with gelatin capsules filled with 67 mg of thioctic acid and 130 mg of indigestible dextrin used in Test Example 1 (3 days a day). Per thioctic acid intake: 200 mg) was divided into 3 portions and was taken after each meal, and this was continued for 2 weeks. The control group (10 persons) received a gelatin capsule filled with 200 mg of indigestible dextrin in the same manner. Two weeks after the start of the capsule ingestion, a questionnaire survey (three-step evaluation) was performed on the psychological effects of each person.

As a result, (1) As for activity motivation, the subject group is strong: 1 person, normal: 6 persons, weak: 3 persons, and the thioctic acid combination capsule intake group is strong: 5 persons, normal: 4 persons, weak: 1 It was a person. (2) Looseness / malaise in the control group: 4 people, normal: 4 people, low: 2 people, and thioctic acid-containing capsule intake group: 2 people, normal: 2 people, low: There were six people. From this, it is recognized that the continuous ingestion of thioctic acids has the effect of reducing the body's dullness and malaise in terms of psychopsychology, and enhancing the spontaneity and motivation such as energy, motivation, and motivation for activity. It was.

(Prototype example 1: Food and drink)
Thioctic acid (manufactured by Degussa, Germany, trade name: ALIPURE (registered trademark), racemic body) 170 parts, beeswax 30 parts and medium chain fatty acid triglyceride (manufactured by Nisshin Oilio Co., Ltd., trade name: ODO (registered trademark) 50 The mixture was heated and mixed to about 50 ° C. to be homogenized, and then subjected to a capsule filling machine, and a gelatin-coated soft capsule preparation with an internal volume of 300 mg per tablet was prepared by a conventional method. It can be used as food.

(Prototype example 2: food and drink)
In Example 1, 170 parts of thioctic acid was replaced with 100 parts of thioctic acid and 70 parts of creatine monohydrate (manufactured by Degussa, Germany, trade name: CREAPURE (registered trademark)). Prototype.

(Prototype example 3: food and drink)
In Example 1, 170 parts of thioctic acid was replaced with 170 parts of a mixture of thioctic acid and guava leaf extract (sample 3) to prepare a dietary supplement.

(Prototype example 4: food and drink)
150 parts of a lipid coating containing thioctic acid, creatine and L-carnitine-L-tartrate (sample 4), 20 parts of red pepper extract powder (manufactured by BN Co., Ltd.), 30 parts of beeswax and 50 parts of evening primrose oil The mixture was thoroughly mixed at about 45 ° C. to obtain a homogeneous state, and then subjected to a capsule filling machine to prepare a gelatin-coated capsule preparation having an inner volume of 250 mg per grain by a conventional method. This capsule preparation can be taken orally as a dietary supplement.

(Prototype example 5: Food and drink)
47 parts of thioctic acid lipid coating (Sample 1), grape seed extract (Kikkoman Co., Ltd., “Grabinol”) 20 parts, cystine 25 parts, lotus germ extract powder (Maruzen Pharmaceutical Co., Ltd.) 20 parts, creatine ( Germany Degussa, same as above.) 25 parts, Riboflavin (DSM Nutrition Japan Co., Ltd.) 7 parts, Maltitol (Towa Kasei Co., Ltd.) 105 parts, Tricalcium phosphate (Yoneyama Chemical Industries) 105 parts and Cellulose 26 parts were charged in a mixer and stirred and mixed for 10 minutes. This mixture was subjected to a direct compression tableting machine to prepare uncoated tablets having a diameter of 7 mm, a height of 4 mm, and a weight of 150 mg / piece, and then a shellac film was formed by the coating machine to produce a tablet-shaped food.

(Prototype 6: Food and drink)
20 g of the thioctic acid double coating (sample 5) of the present invention was added to 1 L of commercially available orange juice and mixed well to produce a homogeneous orange flavored drink. Even if this was stored in the refrigerator for 1 week, the appearance and flavor were neither abnormal nor uncomfortable.

The composition comprising thioctic acids or thioctic acids and creatine of the present invention is ingested by oral or tube administration to enhance basal metabolism, prevent fatigue, accelerate fatigue recovery, obesity It has the effect of preventing lifestyle-related diseases by reducing blood sugar levels and blood lipid levels, and also has a positive impact on psychopsychological aspects such as suppression of malaise and increased activity motivation. Therefore, it can be effectively used for food and drink, medicines, feeds, etc. that are applied for dietary assistance and nutritional supplements in daily activities as well as sports exercise and overloading work.

Claims (5)

An agent for improving activity motivation by enhancing basal metabolism , comprising thioctic acids as an active ingredient (limited to pharmaceutical use) . However, the thioctic acids are one or more selected from the group consisting of thioctic acid, dihydrothioctic acid, optical isomers thereof, salts, esters and amides of the respective substances, and cyclodextrin inclusion products thereof. is there. Thioctic acid is thioctic acid, dihydrothioctic acid, optical isomers thereof, salts, esters and amides of the respective substances, and one or more crystals or powders selected from the group consisting of these cyclodextrin inclusions The agent according to claim 1, wherein the outer surface of the particle is coated with lipids. Thioctic acid is thioctic acid, dihydrothioctic acid, optical isomers thereof, salts, esters and amides of the respective substances, and one or more crystals or powders selected from the group consisting of these cyclodextrin inclusions 2. The agent according to claim 1, wherein the outer surface of the particles coated with lipids is further coated with a hydrophilic substance. The agent according to any one of claims 1 to 3 , wherein the thioctic acid is a racemic thioctic acid. Caffeine, creatine and derivatives thereof (creatine salt, creatine monohydrate, creatine citrate, creatine pyruvate and phosphocreatine) , glucosamine, chondroitin, chondroitin sulfate, collagen Hydrolyzate, choline, phosphatidylcholine, choline salt, serine, phosphatidylserine, methylsulfonylmethane, whey protein, pyruvic acid and its salt, L-carnitine, its precursor lysine or methionine and their salts, D-ribose, Amino acids, branched chain amino acids, taurine, coenzyme Q10, vitamin B1, vitamin B2, nicotinic acid, pantothenic acid, lactoferrin, conjugated linoleic acid, citric acid, malic acid, mineral yeast, ginger, pepper, and hydride Agent according to any one of claims 1-4 from the group consisting of Rokishikuen acids are those used in combination of at least one selected.