JP2018090504A - Muscle enhancing composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a muscle enhancing composition high in muscle enhancing action and including components for which the occurence of side effects are reduced.SOLUTION: The muscle enhancing composition comprises two or more components selected from the group consisting of β-hydroxy-β-methylbutyric acid and/or a salt thereof, red wine and extract thereof, black ginger and extract thereof, and ornithine and a salt thereof. The present invention is expected to be effective not only for the improvement, alleviation, recovery, treatment, or prevention of reduced muscle function such as a decrease in muscle mass, muscle breakdown, muscle fatigue, and decreased exercise capacity, and for various symptoms and diseases caused by reduced muscle function such as sarcopenia, osteoporosis, wrinkles, sagging, but also for increasing muscle mass, muscle strength, getting in shape, body tightening, slimming, and for efficient nutritional intake during training.SELECTED DRAWING: Figure 1

Description

The present invention relates to a composition for enhancing muscles.

If muscle function declines due to aging, lack of exercise, or inability to exercise, walking will be difficult, leading to difficulties in running a normal life. Furthermore, the loss of muscle mass may develop into cosmetic problems such as wrinkles and sagging.

Therefore, a component having a muscle strengthening action and a composition containing the component are desired as preventive improvement or alleviation of muscle function deterioration such as muscle mass reduction, muscle degradation, muscle fatigue, and lowering of exercise ability. . For example, steroid hormones are known as compounds having a muscle enhancing action. However, it is known that taking steroid hormones causes serious side effects such as cardiovascular diseases.

Muscle cell differentiation is regulated by muscle regulatory factors (MRFs) such as myogenin and myoD. When myogenin is expressed starting from MyoD, the downstream cascade functions to differentiate mesenchymal stem cells into muscle cells. Regeneration of muscle through differentiation of muscle cells can be expected to improve or alleviate muscle atrophy resulting from aging or chronic inflammation.

As a component useful for muscle regeneration and repair, β-hydroxy-β-methylbutyric acid (HMB) is known. For example, Patent Document 1 discloses that, by ingesting HMB, muscle precursor cells involved in muscle regeneration and repair are activated and differentiated, and then fused to muscle fibers, so that a new myonucleus is added to the existing muscle. It is described to be found in the fibers.

Special table 2014-506254 gazette

However, according to the investigations by the present inventors, it cannot be said that HMB has a muscle strengthening action such as induction of differentiation into muscle cells. Further, unlike steroid hormones, no ingredient has been known so far that has a high muscle strengthening action but does not cause serious side effects.

Therefore, an object of the present invention is to provide a muscle strengthening composition containing a component having a high muscle strengthening action and reduced side effects.

In order to solve the above-mentioned problems, the present inventors have intensively studied various ingredients, particularly ingredients having a dietary experience. As a result, surprisingly, it cannot be said that the muscle-enhancing effect is sufficient when taken alone. It has been found that when HMB is combined with specific components, it exhibits a large muscle-enhancing effect. Moreover, since the degree of action was significantly greater than when HMB was used alone, the muscle strengthening action obtained by combining HMB with a specific component was synergistic rather than additive. It was an effect.

As a result, the present inventors have succeeded in creating a composition containing HMB and a specific ingredient with a dietary experience as a muscle strengthening composition. The present invention has been completed on the basis of such knowledge and successful examples.

Therefore, according to the present invention, the following compositions [1] to [3] are provided.
[1] Contains β-hydroxy-β-methylbutyric acid and / or salt thereof, and two or more components selected from the group consisting of red wine and extract thereof, black ginger and extract thereof, and ornithine and salt thereof A composition for strengthening muscles.
[2] Muscle enhancement containing β-hydroxy-β-methylbutyric acid and / or its salt, red wine and / or its extract, black ginger and / or its extract, and ornithine and / or its salt Composition.
[3] A composition for enhancing muscle, comprising β-hydroxy-β-methylbutyric acid and / or a salt thereof, and one or more components of red wine and an extract thereof, and black ginger and an extract thereof.

In the composition for enhancing muscles of one embodiment of the present invention, the active ingredients are all ingredients that have dietary experience, and can exhibit a high degree of muscle strengthening action while being safe when ingested. The composition for enhancing muscles according to one embodiment of the present invention has such an action, and is thereby brought about by a decrease in muscle function such as a decrease in muscle mass, muscle degradation, muscle fatigue, and a decrease in exercise ability, or the decrease in muscle function. Not only can it be expected to improve, relieve, recover, treat or prevent various symptoms and diseases such as sarcopenia, osteoporosis, epilepsy, sagging, but also muscle function such as increased muscle mass, increased strength, shape up, slimming It can be expected to meet demands such as strengthening and tightening the body.

FIG. 1 is a diagram showing myogenin mRNA expression levels analyzed using the test substances and control solutions with the Gapdh mRNA expression level as an internal standard, as described in the Examples described later.

Hereinafter, although the detail of the composition for muscle enhancement which is one aspect | mode of this invention is demonstrated, the technical scope of this invention is not limited only by the matter of this item, and this invention achieves the objective. As long as it can take various forms.

The muscle building composition contains at least β-hydroxy-β-methylbutyric acid (HMB) and / or a salt thereof, that is, HMB, a salt of HMB, or both.

HMB, also known as 3-hydroxyisovaleric acid, has a structure in which a hydroxyl group is added to the β-position carbon of 3-methylbutanoic acid. The salt of HMB is not particularly limited as long as it is a commonly known inorganic salt and organic salt of HMB. For example, a metal such as calcium salt, magnesium salt, barium salt, sodium salt, potassium salt, lithium salt of HMB Salt, and the like, preferably calcium salt of HMB.

In addition to HMB and / or a salt thereof, the composition for enhancing muscle further contains at least a specific component (hereinafter also referred to as “subcomponent”). The muscle building compositions are distinguished from each other by the fact that the contained subcomponents can take the following aspects (1) to (3):
(1) Two or more components selected from the group consisting of red wine and its extract, black ginger and its extract, and ornithine and its salt (2) Red wine and / or its extract, black ginger and / or its extraction Ornithine and / or its salt (3) Red wine and its extract, and black ginger and its extract

The red wine is not particularly limited as long as it is obtained by subjecting grape juice to a fermentation treatment as is generally known and storing it as necessary. The red wine may be one in which various components are added to the red wine, such as concentrated fruit juice, soy with added brandy, Port, Madilla, Malaga, Marsala and so-called reinforced wine, Examples include mixed wines such as vermouth, which are obtained by adding medicinal herbs, fragrances, and pigments to red wine.

The black ginger ( Kaempferia parviflora ) is not particularly limited as long as it is known as a plant belonging to the genus Vanucum, which is known to grow naturally in Southeast Asia and the like, for example, its root, stem, leaf, flower, Sites such as branches can be used, but roots and stems are preferred.

The black ginger may be a processed product obtained by subjecting it to a predetermined treatment after being collected, in addition to the unprocessed one in the collected state. Examples of the processed product include, but are not limited to, a dry powder, a fragmented product and a dry powder thereof, a juice and a dry powder thereof, an extract and a dry powder thereof. Specifically, a dry powder is preferable from the viewpoint of ease of processing, storage, transportation, etc. and versatility of usage forms.

The extract of red wine and black ginger is not particularly limited as long as the components in red wine and black ginger are extracted. For example, the components contained in red wine and black ginger are extracted with a solvent in accordance with a conventional method. Extract, the diluted solution or concentrated solution thereof, or the dried product or powder thereof. For example, examples of the component contained in red wine include polyphenols, and examples of the component contained in black ginger include polymethoxyflavonoids such as 5,7-dimethoxyflavone, but are not limited thereto.

Examples of the solvent used for the extraction include water such as normal temperature water, warm water, and hot water; lower alcohols such as ethanol, methanol, isopropanol, and butanol; lower esters such as ethyl acetate and methyl acetate; acetone; Or a mixed solvent thereof. Examples of the mixed solvent include acetone / water (2/8 to 8/2, volume ratio) mixture, ethanol / water (2/8 to 8/2, volume ratio) mixture, and the like.

The extraction method is not particularly limited. For example, a solvent having a mass of 2 to 20 times is added to red wine or black ginger, and the mixture is allowed to stand, shake, and stir for several minutes to several tens of hours in the range of 0 ° C. to the reflux temperature of the solvent. And a method of performing extraction under an arbitrary condition such as reflux. After the extraction operation, it is preferable to perform solid-liquid separation operations such as filtration and centrifugation to remove insoluble solid matter. An extract can be obtained by performing operations such as dilution and concentration as necessary. Further, the same operation may be repeated for insoluble matter, and the extract may be used in combination with the previous extract. These extracts may be used after further purification by a purification method commonly used by those skilled in the art.

A method for obtaining a dried product from the extract is not particularly limited, and examples thereof include a method of subjecting the extract and its concentrate to a drying process commonly used by those skilled in the art, such as spray drying, freeze drying, drying under reduced pressure, and fluidized drying. It is done. Furthermore, the dried product thus obtained can be used after being pulverized by a method known to those skilled in the art.

Ornithine is a kind of amino acid called 2,5-diaminopentanoic acid, as is generally known. The salt of ornithine is not particularly limited as long as it is an inorganic or organic salt of ornithine as is generally known. For example, a metal such as calcium salt, magnesium salt, barium salt, sodium salt, potassium salt, or lithium salt of ornithine. Examples include salt.

Each of HMB and its salt, red wine and its extract, black ginger and its extract, and ornithine and its salt may be produced by a method usually known by those skilled in the art or distributed in the market. It may be a thing.

The composition for enhancing muscle exhibits a muscle enhancing action by containing HMB and / or a salt thereof in combination with the subcomponents of the above aspects (1) to (3). As used herein, the term “muscle enhancing action” refers to, for example, at least one of induction of myoblast differentiation, muscle regeneration and repair, increase in muscle mass, inhibition of muscle degradation, promotion of recovery from muscle fatigue, and improvement of exercise capacity. Or one action. As described in the examples described later, the muscle-enhancing composition can regenerate or repair muscle through differentiation of muscle cells by increasing the expression level of myogenin by myoblasts.

The degree of muscle enhancing action of the composition for enhancing muscles is determined, for example, by examining the expression level of myogenin in vitro using a cell line as described in the examples described later. It is mentioned that it is a grade which becomes larger than the case where HMB is used independently, Preferably it is 1.1 times or more with respect to the case where HMB is used alone, More preferably, when HMB is used alone In contrast, it is 1.5 times or more, more preferably 2.0 times or more when HMB is used alone, and still more preferably 2.5 times or more when HMB is used alone. It is.

The manufacturing method of the composition for muscle enhancement is not specifically limited, For example, it can be set as a solid composition by including each component at room temperature or under heating. Alternatively, this solid composition can be dissolved in a solvent such as water to form a liquid composition. Furthermore, it can be set as a liquid composition by adding and mixing another solid component to the liquid material of each component. In addition, you may pulverize the obtained liquid composition through a drying process. Examples of the drying process in this case include spray drying and freeze drying, but are not limited thereto.

The content of HMB and / or a salt thereof contained in the composition for enhancing muscles and the accessory ingredients of the above aspects (1) to (3) is not particularly limited as long as the muscle enhancing action is recognized. The lower limit value as an oral composition is, for example, 0.0001 wt% or more, preferably 0.001 wt% or more, more preferably 0.01 wt% or more, and the upper limit value is 99 wt% or less with respect to the entire composition. , Preferably 95 wt% or less, more preferably 90 wt% or less. The lower limit of a parenteral composition such as cosmetics is, for example, 0.00001 wt% or more, preferably 0.0001 wt% or more, more preferably 0.001 wt% or more, and the upper limit is 90 wt% or less, preferably 80 wt%. % Or less, more preferably 70 wt% or less.

The composition for muscle enhancement can be used in various forms for the purpose of obtaining a muscle enhancement action. For example, you may utilize for various purposes, without adding a special process. When the muscle strengthening composition is used for oral use, the dosage form is not particularly limited, and may be in the form of, for example, a pharmaceutical composition for muscle strengthening, a quasi-drug composition, and a food or drink composition.

The specific one aspect | mode of the food-drinks composition is a functional food-drinks which are food-drinks which have fixed functionality with respect to a biological body, for example. Functional foods and beverages include, for example, specific health foods and drinks, functional indication foods and drinks, nutritional functional foods and drinks, health functional foods and drinks, special purpose foods and beverages, nutritional supplements and foods, health supplements and foods, supplements, and beauty foods and beverages. In addition to so-called healthy foods and beverages such as foods and beverages for infants, foods and beverages for pregnant women, foods and beverages for specific people such as foods and beverages for elderly people are included. Furthermore, functional food / beverage products include the health food / beverage products to which the health claim based on the food standards of Codex (FAO / WHO Joint Food Standards Committee) is applied.

The amount of intake of the composition for muscle enhancement is not particularly limited, and can be appropriately set according to the degree of muscle mass required by the intake person, the intake mode, and the like. As for the total amount of HMB and / or a salt thereof and subcomponents of the above embodiments (1) to (3), it is 10 to 10,000 mg / kg, preferably 10 to 1,000 mg / kg.

The daily intake of the muscle strengthening composition is not particularly limited. For example, the total amount of HMB and / or a salt thereof and the subcomponents of the above aspects (1) to (3) is 1 to 10 g, preferably 1.5. ~ 4g.

As described above, the usage form of the muscle strengthening composition is not particularly limited. For example, it can be an oral muscle strengthening composition. The form of the composition for enhancing muscle for oral use is not particularly limited, and can be any form. As the form of the composition for enhancing muscle for oral use, for example, a form suitable for oral intake, specifically, liquid, powder, granule, granule, tablet, rod, plate, block, solid, round Shapes, paste shapes, capsule shapes such as hard capsules and soft capsules, caplet shapes, tablet shapes, and gel shapes.

The composition for strengthening muscles can be a container-packed composition filled in a container and sealed. Although the container is not particularly limited, for example, metal such as aluminum, paper, plastic such as PET or PTP, single layer or laminated film bag, retort pouch, vacuum pack, aluminum container, plastic container, bottle, can, etc. The packaging container is mentioned. In order to avoid deterioration over time, the muscle building composition is preferably sterilized by pressurization and / or heating after being packed in a container and sealed.

Although the usage method of the composition for muscle enhancement is not specifically limited, For example, the composition for muscle enhancement can be orally ingested by drinking as it is with water etc. or diluting with water etc. as it is. Depending on the taste of the user, the composition for muscle strengthening and other solid or liquid materials may be mixed and taken orally. When the composition for enhancing muscle is made into an orally disintegrating dosage form, it can be taken orally without water.

The composition for muscle enhancement should just contain HMB and / or its salt and the subcomponent of said aspect (1)-(3) at least, However, These can be combined with another component. . Although it does not specifically limit as another component, For example, a thickener, a brightener, a manufacturing agent, etc. can be used as another component. In addition to these, various excipients, binders, lubricants, stabilizers, diluents, extenders, emulsifiers, colorants, fragrances, perfume oils and the like can be used as other components. The content of other components can be appropriately selected according to the form of the composition for enhancing muscles.

When the composition for enhancing muscle is used as a parenteral composition, it can be used in a form suitable for cosmetics, for example. That is, one aspect of the composition for enhancing muscles is a cosmetic composition. For example, the muscle building composition can be processed into various forms such as lotions, emulsions, gels, creams, ointments, etc., as they are or mixed with additives usually used in cosmetic processing. . Specifically, it can be used as a lotion, cosmetic cream, milky lotion, cream, pack, hair tonic, hair cream, shampoo, hair rinse, treatment, facial cleanser, foundation, hair restorer, aqueous ointment, spray and the like.

The composition for muscle strengthening is due to its muscle strengthening action, so that it is possible to use it for those suffering from symptoms or diseases caused by a decrease in muscle function, such as those with difficulty walking and those with movement disorders, and those who are at risk. It is useful for maintaining health for persons suffering from and at risk of other diseases caused directly and indirectly by reduced muscle function. In addition, the composition for muscle strengthening is not only for middle-aged and elderly people who feel muscle weakness and those who lack exercise, but also increases muscle mass, muscle strength, shape up, body tightening, slimming, efficient nutrition intake during training, etc. It is also useful for young people with the needs of

Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples, and the present invention can take various modes as long as the problems of the present invention can be solved. .

As described below, the expression promotion amount of myogenin (Myogin), which is a differentiation marker of myoblasts, was evaluated by a combination of β-hydroxy-β-methylbutyric acid (HMB) and accessory components.

(1) Test substances The following were used as test substances.
・ HMB: Commercially available HMB calcium ・ Red wine: Commercially available red wine extract (a spray-dried ethanol extract of red wine pomace)
・ Black ginger: Commercially available black ginger extract (Black ginger ethanol extract spray-dried)
Ornithine: Commercially available L-ornithine hydrochloride

Using 2 vol% Horse Serum-DMEM (2% HS-DMEM) differentiation induction medium (0.5% DMSO-2% HS-DMEM) containing 0.5 vol% DMSO as a solvent, the test substance was adjusted to the prescribed concentrations shown below. A test substance solution was prepared by dissolving as follows.
HMB 1000μg / mL
Red wine 6.25μg / mL
Black ginger 6.25μg / mL
Ornithine 50 μg / mL

(2) Test sample The test substance solution is added to 0.5% DMSO-2% HS-DMEM so that the final concentration of the test substance is 50 μg / mL, and the test shown in Table 1 (unit is μg / mL). Samples were prepared.

(3) Cell culture The mouse skeletal muscle-derived cell line C2C12 was cultured in a 75 cm ² flask containing 10 vol% FBS-DMEM medium at 37 ° C in a 5% CO ₂ incubator.

After culturing, cells suspended by trypsin treatment were collected from a 75 cm ² flask, the number of cells was counted, and then seeded at a cell density of 2,000 cells / well in each well of a collagen-coated 96-well plate. The 96-well plate seeded with the cells was cultured in a 37 ° C., 5% CO ₂ incubator for 72 hours.

After the culture, the medium in the well was removed, and 200 μL of 2% HS-DMEM was added to each well for washing. Test samples 1 to 8 were added to each well after washing, and cultured in a 37 ° C., 5% CO ₂ incubator for 24 hours. As a control, 0.5% DMSO-2% HS-DMEM not containing a test sample was added, and 10% FBS-DMEM was added as a negative control without induction of differentiation.

(4) Gene expression analysis After the culture, the medium was removed, and each well was washed once with 200 μL / well of PBS. Subsequently, mRNA was collected using RNeasy Mini Kit (Qiagen), and cDNA was prepared using RiverTra Ace (registered trademark) qPCR RT Master Mix with gDNA Remover (Toyobo).

Quantitative real-time PCR was performed using the obtained cDNA as a template and QuantiNova SYBR Green PCR Kit (Qiagen) using the following primers (Qiagen), and the mRNA expression levels of Gapdh and myogenin were measured.
Gapdh: Mm_Gapdh_3_SG QuantiTect Primer Assay (QT01665892)
Myog: Mm_Myog_1_SG QuantiTect Primer Assay (QT00112378)

Analysis was carried out by relative quantification, and the amount of mRNA was corrected using the amount of Gapdh mRNA expressed as an endogenous control.

(5) Evaluation The measurement result of the myogenin mRNA expression level (relative expression level relative to the endogenous control) by the combination of HMB and subcomponents is shown in FIG. 1 as a relative value when the value of Comparative Example 1 is 1.

As shown in FIG. 1, the myogenin expression level was greater when HMB was combined with subcomponents such as red wine and black ginger than with HMB alone.

And surprisingly, based on the expression level obtained by subtracting the expression level of HMB alone from the expression level of the combination of HMB and red wine or black ginger, the subcomponents to be combined with HMB are more than one type. By using two types, the myogenin expression level increased synergistically rather than additively.

Furthermore, the expression level of myogenin increased dramatically by combining ornithine, which did not affect the expression level of myogenin when combined with HMB alone, with either black ginger, red wine, or both.

From the above results, it was found that HMB promotes the myogenin mRNA expression level when combined with red wine and / or black ginger, and ornithine further enhances this effect. From this, it can be seen that these combinations promote the induction of myoblast differentiation and thus have a muscle strengthening action.

<Production Examples 1-6>
Granules containing HMB, red wine, black ginger and ornithine were prepared according to the formulation shown in Table 2 below.

<Production Examples 7 to 12>
Granules containing HMB, red wine, black ginger and ornithine were prepared according to the formulation shown in Table 3 below.

<Production Examples 13 to 18>
A powdered beverage containing HMB, red wine, black ginger and ornithine was prepared according to the formulation shown in Table 4 below.

<Production Examples 19 to 24>
HMB, red wine, black ginger and ornithine were blended according to the blending shown in Table 5 below, and encapsulated with a film containing gelatin and glycerin to produce a soft capsule.

<Production Examples 25-30>
HMB, red wine, black ginger and ornithine were blended according to the blending shown in Table 6 below, followed by encapsulation with a film containing gelatin to produce a hard capsule.

<Production Examples 31-36>
A liquid beverage containing HMB, red wine, black ginger and ornithine was prepared according to the formulation shown in Table 7 below.

<Production Examples 37 to 42>
Tablets containing HMB, red wine, black ginger and ornithine were prepared according to the formulation shown in Table 8 below.

Since the composition for enhancing muscles according to one aspect of the present invention has a muscle-enhancing effect, it can be used not only for maintaining the health of persons with reduced muscle function, middle-aged and older persons who feel muscle weakness, and those who lack exercise. It is also useful for young people who have demands for increased muscle mass, increased strength, and tightening the body.

Claims (3)

β-hydroxy-β-methylbutyric acid and / or a salt thereof;
A composition for enhancing muscle, comprising two or more components selected from the group consisting of red wine and its extract, black ginger and its extract, and ornithine and its salt. β-hydroxy-β-methylbutyric acid and / or a salt thereof;
Red wine and / or its extract;
Black ginger and / or its extract;
A composition for enhancing muscle, comprising ornithine and / or a salt thereof. β-hydroxy-β-methylbutyric acid and / or a salt thereof;
A composition for strengthening muscle, comprising red wine and its extract, and one or more components of black ginger and its extract.