JP6010665B2 - Muscle bulking agent - Google Patents

Description

  The present invention relates to a muscle bulking agent that can be used for pharmaceuticals and various other uses.

In general, it is known that in order to increase the amount of muscle, it is necessary to apply a load by special exercise such as resistance exercise to the muscle, and to repeatedly destroy and repair the muscle. Moreover, various supplements are used for the purpose of enhancing the effect of increasing muscles due to exercise load.
Resistance exercise is a general term for training with various load resistance applied to muscles, and is also called strength training, weight training, etc., but it improves muscle strength and muscle endurance as well as muscle gain. In addition to weight, various types of load such as elastic resistance, viscous resistance, electromagnetic resistance, etc. have come to be used. Became. In its character, the main purpose is muscle strengthening and hypertrophy (Non-patent Document 1).
Growth hormone is being investigated as a muscle augmentation agent. However, growth hormone has problems such as doping problems and psychosomatic side effects such as hypertension, carcinogenicity, liver damage, testicular atrophy, amenorrhea, delusions, and paranoia. Therefore, it is said that it is not preferable for daily long-term continuous intake. As a diet for muscle strengthening, intake of protein and amino acids, which are muscle materials, is encouraged, but the clear effect is thin and the reality is that there is a great difference between individuals.

  On the other hand, among the extracts obtained from licorice, a licorice hydrophobic extract containing a large amount of licorice flavonoids and having a very small amount of glycyrrhizin was found to be useful for the prevention and treatment of multiple risk factor syndrome. (Patent Document 1). Further, in recent studies, it has been found that this licorice hydrophobic extract has PPARγ ligand activity and that its active ingredient is a flavonoid (Patent Document 2).

  Moreover, the muscle activator which uses a licorice or a licorice extract as an essential component has been reported (patent document 3). The muscle activator here is one that suppresses or improves changes in skin atrophy, wrinkles, sagging, etc. by promoting energy production in muscle cells, that is, ATP production, and improving muscle contraction. . Furthermore, it has been reported that ATP production in muscle cells is synergistically promoted by adding a vitamin C derivative and a vitamin E derivative to the muscle activator shown in Patent Document 3 (Patent Document 4). However, ATP is energy for muscle contraction, and it is considered that vitamin C derivatives and vitamin E derivatives are also added to promote ATP production regardless of muscle gain.

WO02 / 047699 WO03 / 037316 JP 2006-160655 A JP2009-143838A

Original Book 13th edition Medical Physiology Perspective p53-64 Maruzen

An object of the present invention is to provide a muscle bulking agent that does not necessarily require exercise load due to special exercise such as resistance exercise, and can increase muscle mass effectively by ingestion.

Under such circumstances, the present inventors have conducted intensive research, and as a result, the licorice hydrophobic extract obtained by extracting licorice with a non-aqueous solvent having a water content of 15% by weight or less is used as a daily exercise amount. Thus, the inventors have found that there is an effect of effectively increasing muscle mass, and have completed the present invention.
That is, the present invention relates to a muscle bulking agent containing, as an active ingredient, a licorice hydrophobic extract obtained by extracting licorice with a nonaqueous solvent having a water content of 15% by weight or less.

  Since the muscle bulking agent of the present invention exhibits an excellent muscle mass increasing action without performing special exercise, not only as a supplement for muscle weight gain in a healthy body, but also for muscle atrophy suppression or bedridden prevention. It is valid. Since the muscle bulking agent of the present invention has abundant dietary experience and high safety, it can be ingested on a daily basis, so that it can be used not only as a pharmaceutical product but also in various applications.

  Hereinafter, embodiments of the present invention will be described in detail.

  The muscle bulking agent of the present invention is a composition containing, as an active ingredient, a licorice hydrophobic extract obtained by extracting licorice with a nonaqueous solvent having a water content of 15% by weight or less. The “muscle-increasing agent” in the present invention means an agent that has an action of increasing the amount of muscle itself, and is different from a conventional muscle-enhancing agent that activates muscles by promoting energy production in muscle cells. The mechanism for increasing the muscle mass in the present invention is not particularly limited, and all aspects of increasing the absolute amount of the muscle itself regardless of the increase in the number of muscle cells, hypertrophy of the muscle cells, or combinations thereof or other factors. Is included.

The licorice hydrophobic extract which is an active ingredient of the muscle bulking agent of the present invention can be obtained from licorice. The licorice material used as a raw material for the muscle bulking agent of the present invention is not limited as long as it is a plant of the genus Leguminosae (Glycyrrhiza genus). For example, Grykyrieza Inflata (G. inflata). Among them, glycyrrhiza grabra licorice with the widest distribution and rich food experience is preferred.
In the present invention, the method for obtaining the licorice hydrophobic extract from licorice is not particularly limited, but it can be obtained, for example, by extracting licorice or a powder thereof by bringing it into contact with a non-aqueous solvent. Alternatively, the hydrophilic component in licorice can be extracted and removed in advance using water or an alkaline aqueous solution, and then the licorice residue or the dried licorice residue can be used, and similarly, contacted with a non-aqueous solvent. It can also be extracted.

In the present invention, the non-aqueous solvent used as the extraction solvent is not particularly limited as long as it is a solvent other than water, and an organic solvent, oil or a mixed solvent thereof can be preferably used. Although it does not restrict | limit especially as an organic solvent, The safe thing which can be used for manufacture and processing of a pharmaceutical, a foodstuff, a food additive, etc. is preferable, for example, C1-C4, such as acetone, methanol, ethanol, propanol, butanol Examples include monohydric alcohols, polyhydric alcohols such as glycerin and propylene glycol, fatty acid esters, ethers such as diethyl ether, hydrocarbons such as hexane, heptane, and cyclohexane, and a mixture of at least two of these solvents. May be used. Among these, solvents that can be suitably used include fatty acid esters such as ethyl acetate, methanol, ethanol, propanol, butanol, acetone, hexane, heptane, diethyl ether, cyclohexane, propylene glycol, glycerin, and the like. Among them, water-soluble organic solvents such as methanol, ethanol, propanol, butanol, acetone, propylene glycol, and glycerin are preferable, and among water-soluble organic solvents, methanol, ethanol, propanol, butanol, and acetone are more preferable, and ethanol is particularly preferable. preferable. The fats and oils are not particularly limited, and safe ones that can be used for the production and processing of pharmaceuticals, foods, food additives, etc. can be used. As described later, polyhydric alcohol derivatives such as polyhydric alcohol fatty acid esters are used. What is contained is preferable, and as the polyhydric alcohol fatty acid ester, a glycerin fatty acid ester containing a medium-chain fatty acid triglyceride or a glycerin fatty acid ester containing a fatty acid partial glyceride is more preferable. From such a viewpoint, those containing medium-chain fatty acid triglycerides, diglycerides, and mixtures thereof are particularly preferable as fats and oils.
In the present invention, these non-aqueous solvents need to have a water content of 15% by weight or less. In order to sufficiently exert the effect of increasing the muscle mass in the present invention, the water content of the non-aqueous solvent used for extraction is preferably low, for example, 13% by weight (about 10% by volume) or less is preferable, and 10% by weight. % (About 8% by volume) or less, more preferably 8% by weight or less, and particularly preferably 6% by weight or less. The lower limit is not particularly limited, but when a water-soluble organic solvent such as ethanol is used, it is usually 1% by weight or more, preferably 3% by weight or more from the viewpoint of practicality. Of course, a non-aqueous solvent containing no water, that is, having a water content of 0% by volume can also be preferably used.

Extraction of licorice with a non-aqueous solvent can be carried out according to a general method, and is not particularly limited. The extraction temperature is not particularly limited, and can be suitably carried out in the range from the solidification temperature to the boiling point of the system, generally from -20 to 100 ° C, usually from 1 to 80 ° C, preferably from 20 to 60 ° C. The extraction operation is performed, for example, for 0.1 hour or more, preferably 0. Extraction may be performed by bringing licorice and a nonaqueous solvent into contact with each other for 2 hours or longer, more preferably 0.5 hours or longer. Usually, the extraction time per time is preferably about 1 to 10 hours. The upper limit of the extraction time is not particularly limited and is about one day, but it may be performed for a longer time. The extraction may be performed once or a plurality of times as necessary, and the solvents to be used may be appropriately combined. The pressure at the time of extraction is not particularly limited. Normal pressure to pressurized state (1 to several atmospheres) can be used, but reduced pressure can be used if desired. It can also be carried out in a slightly pressurized state under reflux.
In the muscle bulking agent of the present invention, as the licorice hydrophobic extract, the extract obtained as described above may be used as it is, but further purified by a purification step such as column treatment, deodorization treatment, decolorization treatment, etc. Alternatively, a purified product may be used. The licorice hydrophobic extract obtained by the extraction method of the present invention contains a large amount of licorice polyphenol which is a hydrophobic component of licorice. Furthermore, many licorice polyphenols have an antioxidant action and are characterized by having a prenylflavonoid group in the structure of the compound. The content of the licorice polyphenol having a prenylflavonoid group contained in the licorice hydrophobic extract, which is an active ingredient of the muscle bulking agent of the present invention, is usually about 0.01 to 100% by weight as a total amount. Those containing 99% by weight are preferred, those containing 1 to 80% by weight are more preferred, and those containing 3 to 50% by weight are more preferred.

In the muscle bulking agent of the present invention, the licorice polyphenol is selected from the group consisting of glabrene, glabrizine, glabrol, 3'-hydroxy-4'-O-methyl glabridine, 4'-O-methyl glabrizine, and hispagrabridine B. It is preferable to contain at least one selected compound. The compound is a licorice, preferably G. Grubra seed licorice can be obtained by extraction with an organic solvent such as ethanol, hexane, acetone, etc., and the extract may be used as it is, but it is further purified by column treatment, deodorization treatment, decolorization treatment, etc. Alternatively, a purified product may be used. Of course, the compound may be any of those derived from other natural sources such as plants, and those that are chemically synthesized or biosynthesized by cultured cells. Moreover, although the refined | purified thing can be used for this compound, as long as it does not contain an unsuitable impurity as food / beverage products, a pharmaceutical, a quasi-drug, etc., it can also use the roughly refined | purified thing.
Among these compounds, at least one selected from the group consisting of grabridine and comprising grabrene, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, Hispa grabridine B It is preferable to contain a compound. Furthermore, it contains at least one compound selected from the group consisting of glabrizine and glabrene, and also consisting of glabrol, 3′-hydroxy-4′-O-methyl glabridine, 4′-O-methyl glabridine, and Hispa grab lysine B More preferably. In particular, it is most preferable to contain all of grabrene, grabridine, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, and hispagrabridine B.

  Here, glabridin, 3′-hydroxy-4′-O-methylglabridin, 4′-O-methylglabridin, 4′-O-methylglabridin, Hispaglabridin B is a flavonoid classified into isoflavan, and is a compound represented by the following general formula (1).

[Gravidine is R1 = H, R2 = OH; 3′-hydroxy-4′-O-methylgrabridine is R1 = OH, R2 = OCH ₃ ; 4′-O-methylgrabridine is R1 = H, R2 = OCH ₃ ; In Hispagrabridine B, R1 to R2 are —CH═CH—C (CH ₃ ) ₂ —O— to form a six-membered ring. ]
Glabrene is a flavonoid classified into isoflav-3-ene and is a compound represented by the following general formula (2).

  Glabrol is a flavonoid classified as flavanone, and is a compound represented by the following general formula (3).

  Gravuren, glabrizine, glabrol, 3′-hydroxy-4′-O-methyl glabrizine, 4′-O-methyl glabrizine, and hispagrabridine B are mainly contained in licorice mainly in Glycyrrhiza glabra. It is an ingredient. However, G. It may be included in hybrids of grabra and other varieties. The compound can be detected and quantified separately from other flavonoid components by HPLC analysis using a reverse phase column such as ODS.

  In the muscle bulking agent of this invention, it is preferable to contain the said compound in the state melt | dissolved in fats and oils. In this case, the purified or synthesized compound may be directly dissolved in fats and oils and used as an active ingredient of the muscle bulking agent of the present invention. As described later, licorice is extracted with an organic solvent, A method of obtaining a licorice hydrophobic extract containing a compound and contacting the extract with fats and oils is simple and preferred.

  By the way, in the present invention, it is important to increase the active ingredient content in the licorice hydrophobic extract and to keep the content of water-soluble impurities such as glycyrrhizin low. Glycyrrhizin is also used as a medicine, but it has a blood pressure-elevating effect, myocardial damage, and wateremia (Harders, H. & Rausch-Stroomann, JG, Munch. Med. Wschr. 95, 580 (1953)), low Potassiumemia, decreased plasma renin activity, pseudoaldosteronism, relaxed limb paralysis (Conn, JW, Rovner, DR & Cohen, EL, J. Am. Med. Assoc. 205, 492 (1968)), urine It has side effects such as decreased aldosterone excretion, edema, headache, lethargy (above, Epstein, MT, et al., Brit. Med. J., 1, 488 (1977)), and 150 times sweeter than sucrose. There is.

  The incorporation of glycyrrhizin inhibits various effects of the licorice hydrophobic extract, and causes disadvantages in use as a food because of the above-mentioned side effects and strong sweetness. From such a viewpoint, the glycyrrhizin content in the licorice hydrophobic extract in the muscle bulking agent of the present invention is preferably 0.5% by weight or less, more preferably 0.2% by weight or less, and still more preferably 0.01% by weight. % Or below the detection limit (substantially does not contain glycyrrhizin). In order to increase the active ingredient content in the obtained licorice hydrophobic extract and to keep the content of water-soluble impurities such as glycyrrhizin low, it is preferable to reduce the water content coexisting during extraction with a non-aqueous solvent. For that purpose, it is preferable not only to use a non-aqueous solvent having a low water content as an extraction solvent as described above, but generally to use licorice as dry as possible as a raw material. In addition, the licorice form has a high ratio of the skin area to the total surface area, usually 30% or more, preferably 50% or more, more preferably 70% or more, particularly 80% or more, especially 90% or more. It is preferred to use. However, licorice is, of course, a plant, and in order to obtain licorice as dry as possible, it is not always sufficient to carry out sundrying or the like that is usually performed, and it is necessary to use a dryer or the like. This is a major difficulty in production on an industrial scale. In addition, even if a non-aqueous solvent containing no water or having a low water content is used for the first time, it is difficult to completely prevent moisture from being used in licorice and the working environment. It is recovered as an increased non-aqueous solvent. If the water content of the recovered non-aqueous solvent exceeds 15% by weight, it cannot be recycled as it is, so the non-aqueous solvent must be made disposable or a special and expensive purification facility for dehydration is required. In any case, it leads to an increase in manufacturing costs.

In particular, a licorice hydrophobic extract obtained by using a water-soluble organic solvent as an extraction solvent is hardly soluble in water and general oils, and is not easily dissolved in an organic solvent extract. Since it is known to be stable, it is necessary to formulate it in an easy-to-use and stable state. In addition, since an organic solvent is used for extraction, there are problems such as high production costs and a large environmental load. From such a viewpoint, in the present invention, two types of solvents are used as the nonaqueous solvent for extraction. It is preferable to carry out a two-stage extraction in which an extract obtained by contacting licorice with a first nonaqueous solvent is further contacted with another second nonaqueous solvent.
At this time, the first non-aqueous solvent used for the first extraction is preferably an organic solvent. The organic solvent in this case is not particularly limited, and organic solvents such as those described above as the extraction solvent can be used. Among them, methanol, ethanol, propanol, butanol, acetone, heptane, hexane, glycerin, fatty acid ester, diethyl Ether, cyclohexane, propylene glycol and the like are preferable, and ethanol is more preferably used.
Moreover, fats and oils are preferable as the second non-aqueous solvent used for the second stage extraction. In particular, by using fats and oils containing polyhydric alcohol fatty acid esters as fats and oils, the above-mentioned object can be suitably achieved, and furthermore, the fat and oil composition can be used as it is for any application.
Further, the polyhydric alcohol fatty acid ester is preferably contained in the oil or fat in an amount of 10% by weight or more. When the content of the polyhydric alcohol fatty acid ester in the fat is 10% by weight or more, the effect of extracting the licorice hydrophobic extract is sufficiently exhibited. The polyhydric alcohol fatty acid ester in this case is not particularly limited as long as it is an alcohol fatty acid ester having two or more hydroxyl groups in the same molecule. For example, polyhydric alcohol such as glycerin, polyglycerin, sugar, sugar alcohol, polysorbate and the like Examples include fatty acid esters of alcohol. The polyhydric alcohol fatty acid ester used in the present invention is preferably a glycerin fatty acid ester, and more preferably a medium-chain fatty acid triglyceride or a glycerin fatty acid ester mainly composed of a medium-chain fatty acid triglyceride. The content of medium-chain fatty acid triglycerides in the fat used as the second non-aqueous solvent is preferably about 50% by weight or more, more preferably about 70% by weight or more. The medium-chain fatty acid triglyceride here is not particularly limited as long as the fatty acid having about 6 to 12 carbon atoms is a constituent fatty acid, but the fatty acid has about 8 to 10 carbon atoms. The ratio is preferably about 50% by weight or more, more preferably about 70% by weight or more. Further, a medium-chain fatty acid triglyceride having a specific gravity at about 20 ° C. of about 0.94 to 0.96 and a viscosity at about 20 ° C. of about 23 to 28 cP is more preferable. Moreover, as the medium chain fatty acid triglyceride, any of naturally derived ones and those prepared by transesterification can be used.

  In the present invention, the polyhydric alcohol fatty acid ester may be a fatty acid partial glyceride or a glycerin fatty acid ester mainly composed of a fatty acid partial glyceride. In that case, the content of the fatty acid partial glyceride in the fat used as the second non-aqueous solvent is preferably about 50% by weight or more, more preferably about 70% by weight or more. The fatty acid partial glycerides here are diglycerides (1,2-diacylglycerol, 1,3-diacylglycerol) or monoglycerides (1-monoacylglycerol, 2-monoacylglycerol), and any of them may be used. A mixture of the two may be used, and the constituent fatty acid is not particularly limited, but diglycerides having an unsaturated fatty acid and / or a medium chain fatty acid as the constituent fatty acid are preferred from the viewpoint of processability. In addition, as the fatty acid partial glyceride, any of those derived from nature, those prepared by transesterification, and the like can be used.

  Furthermore, as the fats and oils used in the present invention, those obtained by mixing the medium chain fatty acid triglyceride and the fatty acid partial glyceride may be used.

  In the present invention, there are no particular limitations on the method of extracting licorice in two stages using two types of non-aqueous solvents as described above. For example, the first extraction described above, preferably, licorice is contacted and mixed with an organic solvent. The licorice organic solvent extract obtained by extraction can be obtained by dissolving in a second non-aqueous solvent, preferably an oil or fat. In this case, the licorice organic solvent extract may be in the form of an extract or from which the solvent is removed. Dissolution of the licorice organic solvent extract in the second non-aqueous solvent can be carried out by ordinary operations such as stirring or mixing, but the licorice organic solvent extract is dissolved in fats and oils by operation such as stirring or mixing, followed by filtration. Alternatively, it is desirable to remove impurities that are insoluble in fats and oils by an operation such as centrifugation because the content of water-soluble components such as glycyrrhizin can be reduced as much as possible. In order to increase the extraction efficiency, it is preferable that the mixture is heated to 30 to 100 ° C., more preferably 40 to 90 ° C., and preferably mixed and stirred. In order to prevent deterioration due to heating, mixing is performed under reduced pressure or in a nitrogen stream. More preferably, stirring is performed. The mixing and stirring time is not particularly limited, but is preferably 1 hour or longer, more preferably 1 to 5 hours, and further preferably 1 to 3 hours. Or the method of WO03 / 84556 can also be used conveniently. For example, it is possible to extract directly from a licorice raw material with an organic solvent and fat, but it can also be obtained by mixing the fat and oil into an extract obtained by extracting licorice with an organic solvent and then removing the organic solvent. Preferably, by mixing the licorice raw material with ethanol and then mixing unnecessary oil and fat, preferably medium-chain fatty acid triglycerides, in ethanol solution of licorice extract obtained by contact mixing with ethanol, and then removing ethanol. Can be obtained. Furthermore, in this invention, you may add fats and oils with respect to the mixture of these licorice hydrophobic extracts and fats and oils, and may adjust the composition ratio of a licorice hydrophobic extract and fats and oils.

  Generally, a hydrophobic licorice hydrophobic extract is unstable in a powder state, and its stability is not improved even when dissolved in an organic solvent such as ethanol. However, the stability can be improved by dissolving the extract in fats and oils by the preferred method described above. Moreover, since the licorice hydrophobic extract is sparingly water-soluble, it can be expected that its absorbability is improved by using it in a state dissolved in fats and oils. In that case, the properties of the extract are preferably liquid or slurry.

  By performing such two-stage extraction, a high-quality licorice hydrophobic extract having a high active ingredient content and a low water-soluble impurity content can be suitably obtained. The glycyrrhizin content in the licorice hydrophobic extract obtained by the above two-stage extraction is preferable even when an organic solvent containing some water is used as the first non-aqueous solvent and the licorice used as a raw material is insufficiently dried. Can be minimized to 0.5 wt% or less, more preferably 0.2 wt% or less, even more preferably less than 0.01 wt% or below the detection limit. In addition, by performing two-stage extraction, a high quality extract can be suitably obtained even when an inexpensive organic solvent containing water is used as an extraction solvent without specially drying licorice, thus simplifying the manufacturing process. A great advantage can be expected in terms of cost and cost reduction.

  The form of the muscle bulking agent of the present invention containing the licorice hydrophobic extract obtained by the above method is not particularly limited. For example, in the form of hard capsule, soft capsule, tablet, powder, syrup, drink, etc. And can be used for other purposes. Oils and fats in which at least one compound selected from the group consisting of grabrene, grabridine, grabrol, 3′-hydroxy-4′-O-methyl grabridine, 4′-O-methyl grabridine, and Hispa grabridin B is dissolved Can be used alone for cooking or for soft capsule preparations. Furthermore, since the mixture of the licorice hydrophobic extract obtained by the said preferable method and fats and oils can be freely mixed with an oily object, it can mix with other fats and oils according to the objective, and can adjust a physical property. Is possible. In this case, it is preferable that the other fats and oils are foods or pharmaceuticals, and the type and use amount thereof are determined in consideration of various conditions such as physical properties and use temperature range required for each product. By adjusting the amount, characteristics such as consistency and melting point can be controlled. For example, vegetable oil such as corn oil, rapeseed oil, Haier rapeseed oil, soybean oil, olive oil, safflower oil, cottonseed oil, sunflower oil, rice bran oil, palm oil, palm kernel oil, fish oil, beef tallow, lard, milk fat, egg yolk oil An oil composition can be obtained by using animal oils such as these, oils and fats that have been subjected to fractionation, hydrogenation, transesterification, etc., or mixed oils thereof. The oil / fat composition thus obtained can be used as liquid oil / fat such as salad oil and frying oil, plastic oil / fat such as margarine and shortening, water-in-oil emulsion, and oil-in-water emulsion.

  Furthermore, for the purpose of fortification, various vitamins such as vitamins A, D, and E may be added and used together. Various salts as flavoring agents, various flavorings, milk-related substances such as whole milk powder, You may add skim milk powder, fermented milk, milk fat, etc., and may use together. Further, as raw materials other than the above, all of the antioxidants, colorants and the like used in ordinary water-in-oil emulsions and oil-in-water emulsions can be used.

  In addition to the licorice hydrophobic extract, the muscle bulking agent of the present invention may contain a carrier that is acceptable for food and drink or for medicine. The pharmaceutical carrier can be any inert, organic or inorganic material suitable for oral, enteral, transdermal, subcutaneous, or parenteral administration, including but not limited to water, gelatin, gum arabic, lactose , Microcrystalline cellulose, starch, sodium starch glycolate, calcium hydrogen phosphate, magnesium stearate, talc, colloidal silicon dioxide, and the like. Such compositions may also contain other pharmacologically active pharmaceutical ingredients, and conventional additives such as stabilizers, wetting agents, emulsifying agents, flavoring agents, buffering agents and the like.

  In the present invention, the effect of increasing the muscle mass can be confirmed by a method in which a test sample is given using an animal (mouse, rat, etc.) and the muscle weight is measured. The sample may be fed into food or drinking water, or may be forcibly orally administered using a sonde or the like. An increase in muscle mass can be confirmed by devising the administration timing of the test sample. Moreover, the effect can also be confirmed by actually administering to a human.

  The muscle bulking agent of the present invention can exert a muscle weight gain effect without performing the specific exercise conventionally required for muscle weight gain. Therefore, it is expected to increase or maintain muscle mass even when administered to subjects who are difficult to exercise due to exercise, such as bedridden sick people, patients with injuries or illnesses that need to rest for a certain period of time, elderly people who have difficulty with intense exercise, etc. It can also be expected to prevent bedridden and prevent muscle atrophy. In addition, administration in combination with daily exercise can also exert a muscle gain effect. Daily exercises here include not only jogging, flexible gymnastics, esthetic gymnastics, and other hobby sports, but also light work such as commuting, work and housework. Specific calorie consumption in daily exercise is not particularly limited by the gender and age of the subject, for example, as calorie consumption per 30 minutes 50 kcal or more, preferably 60 kcal or more, more preferably 80 kcal or more, As the upper limit, exercise and work up to 140 kcal correspond to daily exercise. The degree of performing daily exercise is not particularly limited, and may be set as appropriate according to the age, weight, purpose, and lifestyle of the subject. For example, the total calories consumed including daily exercise per day It may be 1500 kcal or more, preferably about 1700 kcal or more. The upper limit is not particularly limited, and it goes without saying that the higher the total calorie consumption, the higher the effect tends to be obtained. However, when taking the muscle bulking agent of the present invention, for example, about 2300 kcal, preferably about 2100 kcal. Even with the total calories burned, the effect can be obtained sufficiently.

  In addition, the muscle bulking agent of the present invention can exert a more preferable effect even when administered in combination with a resistance exercise that has been conventionally effective for muscle weight gain. The resistance exercise here is an exercise that is performed with a certain load on the muscle, and the method of applying the load is not particularly limited, but besides barbells and machines, appropriate heavy objects, water, expanders, A rubber tube can be used.

  The combination of the above exercise and the muscle bulking agent of the present invention is not particularly limited as long as it is a form in which the intake of the muscle bulking agent of the present invention and the above exercise are used in combination within a certain period. Not limited. In addition, in the present invention, in order to be administered to an administration subject that is difficult to load due to exercise, or to be combined with the above-mentioned daily exercise or resistance exercise, its use form is exemplified and recommended in a catalog or the like, or a doctor May be recommended as a preferable method from sports instructors and other professionals, and these are also within the scope of the present invention.

Furthermore, the licorice hydrophobic extract, which is an active ingredient of the muscle bulking agent of the present invention, not only increases the muscle weight but also suppresses body fat accumulation, the body fat degradation promoting effect, and the energy production promoting effect, which are the main causes of metabolic syndrome. (WO 2008-143182), blood glucose level increase inhibitory effect (Biol. Pharm. Bull. 27 (11) 1775-1778 (2004)), blood blood neutral fat level increase suppression, blood free fatty acid level It also has an excellent effect of suppressing the rise. That is, the muscle bulking agent of the present invention can be used not only for increasing muscle mass but also for the purpose of preventing obesity, diabetes and hyperlipidemia.
The method for ingesting the muscle bulking agent of the present invention is not particularly limited, but it is preferable to ingest it on a daily basis. The intake route is not particularly limited, but oral administration is simple and preferable. The amount of intake is not particularly limited, but in terms of the amount of licorice hydrophobic extract, the amount in the range of 30 to 600 mg / dose or 30 to 600 mg / day is preferable for adults, and 50 mg to 500 mg / dose or 50 to 500 mg / d An amount in the range of days is more preferred, and an amount in the range of 80 mg to 300 mg / dose or 80 to 300 mg / day is even more preferred.
The muscle bulking agent of the present invention can be used not only for humans but also for livestock for the purpose of improving meat productivity, for the purpose of improving the performance of racehorses, and for the purpose of maintaining the health of pets. In this case, it can be administered directly orally or by mixing with feed.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

  49.25 L of 95% ethanol (water content 5% by weight) was added to 9.85 kg of licorice (Glyquiryza grabra), extracted twice at 45 ° C. for 2 hours, and then concentrated to obtain 4.4 L of a concentrated solution. . Among them, 3 L was further concentrated, treated with activated carbon, and further concentrated to obtain 81.2 g of an ethanol solution containing a licorice hydrophobic extract.

  629.2 g of ethanol solution (containing 125.8 g of licorice hydrophobic extract) and medium-chain fatty acid triglyceride (MCT, water content of about 0% by volume) (actor M-2, manufactured by Riken Vitamin Co., Ltd., fatty acid composition Was mixed with 187.6 g of C8: C10 = 99: 1) and stirred for about 1 hour while being kept at about 80 ° C., and then ethanol was removed by concentration under reduced pressure. Insoluble matter was separated by suction filtration, and 45.7 g of MCT was further added to the filtrate after filtration to obtain 297.0 g of MCT solution. 1 g of the obtained MCT solution was dissolved in methanol for HPLC to make a total amount of 100 ml, and this solution was used as a sample for HPLC analysis under the following conditions. As a result, grabrene, grabridine, grabrol, 4 g It turned out that 6.6 mg, 30.8 mg, 12.6 mg, and 3.7 mg of '-O-methyl glabridine are contained, respectively. The content of the licorice hydrophobic extract in the MCT solution was about 30% by weight.

(HPLC analysis conditions)
As the analytical column, J'sphere ODS-H80, 4.6 × 250 mm (YMC) was used at a column temperature of 40 ° C. In the mobile phase, the acetonitrile ratio with respect to the 20 mM phosphoric acid aqueous solution is kept constant at 35% from the start of analysis to 20 min, and is increased at a constant ratio so that it becomes 70% after 75 min after 20 min, and 80% from 75 min to 80 min. The flow rate was 1 ml / min under a constant gradient condition. The injection volume was 20 μl, and the detection wavelength was 254 nm. The retention time of each compound is 40.0 min for grabrene, 50.2 min for grabridine, 58.3 min for grabrol, and 66.8 min for 4′-O-methyl grabridine.

(Comparative Example 1)
4.9 L of 80% ethanol (water content 20% by weight) was added to 1.0 kg of licorice (Glyquiryza grabra), extracted twice at 45 ° C. for 2 hours, and then concentrated to obtain 0.4 L of a concentrated solution. . The solution was further concentrated, treated with activated carbon, and further concentrated to obtain 90 g of an ethanol solution containing a licorice extract. Finally, ethanol was evaporated by an evaporator to obtain a licorice extract 18.1. A licorice extract solution in which this extract and MCT were mixed and dissolved at a ratio of 3: 7 was obtained.

Spontaneous obesity type 2 diabetes model KK- ^Ay / Ta Jcl male mice (CLEA Japan, Inc.) were purchased at 5 weeks of age, acclimated for 1 week, and used for experiments at 6 weeks of age. The mice were divided into 4 groups of 6-7 animals so that the body weight was equal. A group (control group) in which 5 mL / Kg (body weight) of daily distilled water was orally administered by gavage daily, and the licorice extract solution obtained in Comparative Example 1 was gavaged daily to give 1.0 g / kg (body weight). Group (comparison group), a group (sample 1.0 g / kg group) forcibly orally administered MCT solution containing the licorice hydrophobic extract obtained in Example 1 every day to 1.0 g / kg (body weight), The MCT solution containing the licorice hydrophobic extract obtained in Example 1 was mixed with the feed so as to be 1.0% (w / w), and a group (free sample group of 1.0%) was set. . During the test period, each group of mice was reared in a cage in a state where they could perform daily exercise. Four weeks after the start of administration, the mice were anesthetized with isoflurane and laparotomized. After blood was collected from the inferior vena cava, the thigh muscles were collected and weighed. The results are shown in Tables 1 and 2.

  In Tables 1 and 2, when compared with the control group, both the group in which the MCT solution containing the licorice hydrophobic extract by two-stage extraction was forcibly administered orally and the group that was freely mixed with the feed were ingested. A significant increase in muscle weight was observed. However, a significant increase in muscle weight was not observed in the group to which licorice extract solution obtained by extracting licorice with 80% ethanol by gavage was administered. That is, a licorice extract obtained by using ethanol having a water content of 20% by weight as an extraction solvent does not have a sufficient muscle weight increasing effect, and the water content of the extraction solvent has an important influence on the effect of the present invention. I understood that.

Production of Soft Capsule The MCT solution containing the licorice hydrophobic extract of Example 1 was pressed into a gelatin film using a rotary soft capsule production apparatus to obtain a soft capsule having an internal volume of 350 mg.

Production of margarine 80 parts by weight of hardened cottonseed oil (trade name: Snowlight, Kaneka Co., Ltd.), 20 parts by weight of MCT solution containing the licorice hydrophobic extract of Example 1, unsalted butter (manufactured by Yotsuba Dairy Co., Ltd.) ) To 10 parts by weight, 0.2 part by weight of glycerin monofatty acid ester (trade name: Emergy MS, manufactured by Riken Vitamin Co., Ltd.) and 0.2 part by weight of lecithin are added and dissolved at 60 ° C. to prepare an oil phase. did.

  While stirring, 15.1 parts by weight of water was added to 84.9 parts by weight of the prepared oil phase, emulsified for 20 minutes, and then cooled and kneaded with a combinator to prepare margarine.

Preparation of concentrated milk After heating 10 parts by weight of the MCT solution containing the licorice hydrophobic extract of Example 1 to 70 ° C., 0.1 parts by weight of lecithin and 0.1 parts by weight of polyglycerol fatty acid ester were dissolved in order to obtain oil. A phase was prepared.

  An aqueous phase was prepared by dissolving 25 parts by weight of skim milk powder, 0.1 part by weight of glycerin fatty acid ester and 0.1 part by weight of sucrose fatty acid ester in 64.6 parts by weight of water at 60 ° C.

  The prepared aqueous phase and oil phase were pre-emulsified, and then sterilized with a UHT sterilizer at 145 ° C. for 4 seconds. Next, after vacuum cooling, the mixture was homogenized with a homogenizer at a pressure of 10 MPa, and further cooled to 10 ° C. to obtain concentrated milk for processing.

Production of mayonnaise 10 parts by weight of brewed vinegar, 1 part by weight of salt, 0.6 parts by weight of sugar, 0.2 parts by weight of mustard powder and 0.2 parts by weight of sodium glutamate are added to the mixer at 15-20 ° C. The aqueous phase was prepared by stirring and mixing. Then, 10 parts by weight of egg yolk was added to 68 parts by weight of rice white squeezed oil and 10 parts by weight of MCT solution containing the licorice hydrophobic extract of Example 1, and a little emulsified liquid (10-15 ° C) obtained by stirring and emulsifying The mixture was stirred at 15 to 20 ° C. while adding, and pre-emulsified. Subsequently, final emulsification was performed using a colloid mill to obtain mayonnaise.

Claims (5)

Patients with bedridden sickness, injuries or illnesses that need to rest for a certain period of time, using a muscle bulking agent containing licorice hydrophobic extract obtained by extracting licorice with a non-aqueous solvent with a moisture content of 15% by weight or less as an active ingredient or strenuous exercise is to feed difficult old man, muscle amount of increase or maintain method (except for medical care for the people). Nonaqueous solvent is an organic solvent, oils or increasing or maintaining the method of muscle mass according to claim 1 Symbol mounting a mixed solvent thereof. The licorice hydrophobic extract is obtained by contacting an extract obtained by contacting licorice with a first non-aqueous solvent and further contacting with a second non-aqueous solvent. 1 or 2 muscle mass increase or maintenance method according. The first nonaqueous solvent is claim 3 muscle mass increase or maintenance method wherein the organic solvent. The second nonaqueous solvent is, claim 3 or 4 muscle mass increase or maintenance method wherein the fat.