JP6071092B2 - Disuse muscular atrophy inhibitor, food / beverage composition for disuse muscular atrophy control, and method for producing food / beverage composition for disuse muscular atrophy control - Google Patents

Description

  The present invention relates to a disuse muscular atrophy-suppressing agent that suppresses disuse muscular atrophy, a food / beverage product composition for suppressing disuse muscular atrophy, and a method for producing a food / beverage composition for suppressing disuse muscle atrophy.

  As muscle atrophy, for example, muscle atrophy (disuse muscle atrophy) in which muscles atrophy due to aging or bedridden is known, and foods and beverages that suppress such waste muscle atrophy have been proposed (see Patent Document 1). ). Patent document 1 is disclosing the muscle atrophy suppression composition which contains fruit polyphenol as an active ingredient. In the same literature 1, the Example of the muscular atrophy suppression composition containing apple polyphenol is disclosed. Here, there is a report that oxidative stress is a factor for disuse muscle atrophy (see Non-Patent Document 1). Non-Patent Document 1 reports that the progression of muscle atrophy can be suppressed by preventing oxidative stress by administering an antioxidant or an iron chelator.

JP 2001-89387 A

Physical Fitness Research, 1993, No. 83, pp. 73-81

  The apple polyphenol described in Patent Document 1 contains catechin having antioxidant activity. As described in Non-Patent Document 1, catechins having antioxidant activity are considered to reduce oxidative stress and consequently suppress disuse muscle atrophy. Catechin is a kind of flavanol, and this flavanol is a kind of flavonoid.

  In addition to flavanols, flavanones are known as a group of compounds classified as flavonoids. Here, since naringenin, which is a typical flavanone, also has an antioxidant activity, an effect of suppressing disuse muscle atrophy is expected. However, the present inventors have confirmed that when a food or drink containing naringenin is ingested, the effect of suppressing disuse muscle atrophy cannot be obtained. Under such circumstances, the present invention has been made by finding that flavanone having a prenyl group added suppresses disuse muscle atrophy.

  An object of the present invention is to provide an agent for inhibiting disuse muscle atrophy that suppresses disuse muscle atrophy, a food / beverage composition for inhibiting disuse muscle atrophy, and a method for producing a food / beverage composition for inhibiting disuse muscle atrophy. Is to provide.

  The disuse muscular atrophy inhibitor for solving the above problems is a disuse muscular atrophy inhibitor used to obtain a food / beverage composition for disuse muscle atrophy suppression by blending in a food / beverage product, It contains at least one of a grasshopper extract and 8-prenylnaringenin as an active ingredient, and the leafhopper extract contains nymphaeol-A, nymphaeol-B, isonympheol-B, nymphaeol-C, and 3'-geranylnaringenin. contains.

The food / beverage product composition for suppressing disuse muscular atrophy that solves the above problems contains the agent for suppressing disuse muscular atrophy.
The manufacturing method of the food-drinks composition for the disuse muscular atrophy suppression which solves the said subject is Nymphaeol-A, Nympheol-B, Isonimpheol-B, Nimpheol-C, and 3'-geranylnaringenin The extract and at least one active ingredient of 8-prenylnaringenin are blended in the food or drink.

  ADVANTAGE OF THE INVENTION According to this invention, the manufacturing method of the food / beverage products composition for waste muscle atrophy suppression, the food / beverage product composition for waste muscle atrophy suppression, and the food / beverage food composition for waste muscle atrophy suppression which suppress waste muscle atrophy. Is provided.

The graph which shows the ratio of the weight of the atrophied muscle with respect to the normal muscle in Example 1 and Comparative Example 1. FIG. The graph which shows the food intake with respect to the breeding organization of the mouse | mouth in Example 1 and Comparative Example 1. FIG. The graph which shows the ratio of the weight of the atrophied muscle with respect to the normal muscle in Example 3. FIG.

The embodiment which materialized the muscular atrophy inhibitor of this invention and its usage is described in detail.
The muscle atrophy inhibitor of this embodiment suppresses disuse muscle atrophy by containing prenylated flavanone as an active ingredient. Muscle atrophy is classified into progressive muscle atrophy and disuse muscle atrophy. Progressive muscular atrophy is a disease group in which skeletal muscles such as extremities progressively atrophy, while disuse muscular atrophy is muscular atrophy caused by not using muscles.

  Examples of prenylated flavanones include prenylated naringenin, prenylated eriodictiool, and prenylated hesperetin. These prenylated flavanones may be used alone or in combination of plural kinds of prenylated flavanones.

  Specific examples of the prenyl group include dimethylallyl group (C5), geranyl group (C10), farnesyl group (C15), geranylgeranyl group (C20), geranylfarnesyl group (C25), hexaprenyl group (C30), octaprenyl group ( C40), and a decaprenyl group (C50).

  Among prenylated flavanones, prenylated naringenin and prenylated eriodictiool are components contained in giant grass (large leaf tree). For this reason, when a prenylated naringenin or a prenylated eriodictiol is contained in a muscle atrophy inhibitor, a giant bug can be used.

  The grasshopper is a plant called Macaranga tanarius, and is an evergreen broad-leaved tree (synergistic male and female) belonging to Euphorbiaceae. Weow grows in Okinawa, Taiwan, southern China, the Malay Peninsula, Southeast Asia such as the Philippines, Malaysia, Indonesia, and Thailand, and northern Australia. In addition, weow grows very fast among trees and can grow in degraded areas. For this reason, according to the muscular atrophy inhibitor containing at least one of prenylated naringenin and prenylated eriodictiool as prenylated flavanone, for example, the above-mentioned grasshopper can be used effectively.

The grasshopper contains 5,7,4′-trihydroxy-3′-geranylflavanone as a prenylated naringenin.
Examples of prenylated eriodictiool contained in the wolfweed include nymphaeol-A, nymphaeol-B, isonymfeol-B and nymphaeol-C. Nymphaeol-A is 5,7,3 ′, 4′-tetrahydroxy-6-geranylflavanone (5,7,3 ′, 4′-tetrahydroxy-6-geranylflavanone). Nymphaeol-B is 5,7,3 ′, 4′-tetrahydroxy-2′-geranylflavanone (5,7,3 ′, 4′-tetrahydroxy-2′-geranylflavanone). Isonymphaeol-B is 5,7,3 ′, 4′-tetrahydroxy-5′-geranylflavanone (5,7,3 ′, 4′-tetrahydroxy-5′-geranylflavanone) is there. Nymphaeol-C is 5,7,3 ′, 4′-tetrahydroxy-6- (3 ″ ″, 3 ″ ″-dimethylallyl) -2′-geranylflavanone (5,7, 3 ′, 4′-tetrahydroxy-6- (3 ′ ″ ″, 3 ′ ″ ″-dimethylallyl) -2′-geranylflavanone).

  From the viewpoint that it is easy to increase the concentration of at least one of prenylated naringenin and prenylated eriodictiool, it is preferable that the grasshopper is blended in the muscle atrophy inhibitor as an extract.

  As a raw material for the plant extract, various organs and components of the plant can be used. As a raw material, a single organ or component may be used, or two or more organs or components may be mixed and used. Specific examples of raw materials include fruits, seeds, flowers, roots, stems, stem tips, leaf blades, and secretions (such as wax). Since the tip of the stem includes the growth point of the stem and the leaf bud and is more flexible than the leaf blade, it is easy to perform the extraction operation efficiently. In addition, when the proportions of the respective organs with respect to the whole of the grasshopper are compared, the proportions of the trunk, roots, and leaves are high. For this reason, it is industrially suitable from the viewpoint that it is easy to secure the raw material to use the leaf of the grass as a raw material for the extract of the grass. In addition, among each part of the grass, flowers, seeds and fruits (including wax) contain nymphaeol-A, B, C and isonymfeol-B at high concentrations. For this reason, in order to raise the density | concentration of prenylated eriodictiool, it is preferable to use a flower, a seed, and a fruit (a wax is included), and it is more preferable to use a fruit.

  The raw material of the grasshopper extract is as it is collected, crushed, crushed or ground after collection, crushed, crushed or ground after collection or drying, or crushed, crushed or ground after collection and dried Used as From the viewpoint of efficiently performing the extraction operation, it is preferable to use a crushed raw material. For such crushing, for example, a cutter, a cutter, a crusher, or the like can be used. Moreover, when preparing the grind | pulverized raw material, a mill, a crusher, a grinder etc. can be used, for example. In preparing the ground material, a kneader, a mortar, or the like can be used.

  As an extraction solvent for extracting a grasshopper extract, an extraction solvent containing at least an organic solvent is preferable. As the extraction solvent, for example, an organic solvent such as a mixed solvent of water and an organic solvent, lower alcohol, dimethyl sulfoxide, acetonitrile, acetone, ethyl acetate, hexane, glycerin, and propylene glycol is preferable. Examples of the lower alcohol include methanol, ethanol, propanol, isopropanol, butanol and the like. As an organic solvent, a single species may be used, or a mixed solvent obtained by mixing a plurality of species may be used. When a mixed solvent of water and an organic solvent is used as the extraction solvent, the content of the organic solvent in the mixed solvent is preferably 50% by volume or more, more preferably 80% by volume or more. When the content of the organic solvent in the mixed solvent is less than 50% by volume, it may be difficult to efficiently extract prenylated naringenin or prenylated eriodictyol. In addition, as an organic solvent, a lower alcohol is preferable and ethanol is more preferable.

In addition, you may dissolve organic salt, inorganic salt, a buffering agent, an emulsifier, dextrin, etc. in an extraction solvent.
As the extraction operation, the raw material is immersed in the extraction solvent for a predetermined time. In such an extraction operation, a stirring operation, heating, or the like may be performed as necessary to increase the extraction efficiency. Further, in order to reduce impurities extracted from the raw material, a separate water extraction operation or hot water extraction operation may be performed prior to the extraction operation. Since prenylated naringenin and prenylated eriodictiool are components insoluble in water, unnecessary impurities can be efficiently removed by boiling the grass with, for example, hot water.

  After the extraction operation, a solid-liquid separation operation is performed, so that the grasshopper extract and the raw material residue can be separated. As a separation method for the solid-liquid separation operation, for example, a known separation method such as filtration or centrifugation can be used.

  Here, the grasshopper includes flavanones other than the above prenylated flavanones. In this regard, for example, by separating the Ooba extract using a column, it is possible to easily obtain an extract (extract) containing prenylated naringenin or prenylated eriodictiool at a high concentration. As a packing material used for the separation operation using a column, a known packing material can be appropriately selected and used. As the filler, for example, silica gel bonded with octadecyl groups is suitable. Confirmation and quantification of prenylated naringenin or prenylated eriodictiool contained in the extract can be performed, for example, by well-known high performance liquid chromatography.

  The obtained grass extract may be concentrated as necessary. By removing the extraction solvent contained in the extract, if necessary, an oily or solid extract can be obtained. Such removal of the solvent may be performed, for example, by heating under reduced pressure or by freeze-drying.

  For example, excipients, additives, auxiliary materials, bulking agents, and the like can be appropriately added to the muscle atrophy inhibitor. The muscle atrophy inhibitor can be used in combination with pharmaceuticals or pharmaceuticals. Examples of the administration method when used as a pharmaceutical product or mixed with a pharmaceutical product include administration by oral administration (oral administration), enteral administration (enteral administration), skin poultice (transdermal) Administration), intramuscular injection and the like. Specific examples of pharmaceutical dosage forms include gum formulations, powders, powders, granules, tablets, capsules, pills, suppositories, liquids, coatings, patches, injections, and the like.

Next, the usage method of a muscular atrophy inhibitor is demonstrated.
The method for using a muscle atrophy inhibitor is the above-described muscle atrophy inhibitor mixed with food and drink.
Specific examples of foods and drinks include quasi-drugs, health foods, foods for specified health use, health drinks, nutritional supplements and the like in addition to normal foods and drinks. Examples of the form of food and drink include gums, powders, tablets, granules, liquids (drinks, etc.), capsules, syrups, candies and the like. More specifically, as foods and drinks, sports drinks, tea beverages extracted from tea leaves and herbs, dairy products such as milk and yogurt, foods containing gelling agents such as pectin and carrageenan, glucose, sucrose, and fructose And beverages and foods containing sugars such as lactose and dextrin, flavorings, sweeteners such as stevia, aspartame, sugar alcohols, and fats and oils such as vegetable oils and animal fats.

  The prenylated flavanone is blended in the food or drink according to a conventional method, for example, by mixing the prenylated flavanone with the base material of the food or drink. In the range which does not impair the objective of this invention, you may add an excipient | filler, an additive, a subsidiary material, a bulking agent, etc. to food-drinks suitably.

  Content of the prenylated flavanone in food-drinks shall be the range of 0.0001-5 mass%, for example. Although the intake of food and drink is not particularly limited, the intake of prenylated flavanone per day for an adult is preferably 1 to 1000 mg, more preferably 10 to 200 mg.

Next, the effect | action of a muscular atrophy inhibitor and its usage method is demonstrated.
Naringenin, which is a typical flavanone, has antioxidant activity, but when naringenin is ingested, the effect of suppressing disuse muscle atrophy is not confirmed. From this, it is speculated that the suppression of disuse atrophy is not necessarily based on reducing the oxidative stress by the antioxidant ability described in Non-Patent Document 1 described above. Moreover, even if a prenyl group is introduced into naringenin, the antioxidant activity is not significantly increased. For this reason, it is estimated that the effect which suppresses disuse muscular atrophy by prenylated flavanone is not based on antioxidant ability, but by another action mechanism. In this regard, in prenylated flavanones, for example, the lipophilicity is increased by the prenyl group, so that it is presumed that the effect of suppressing disuse muscle atrophy is exhibited based on a new mechanism of action that cannot be obtained with flavanones.

  The muscle atrophy inhibitor and the method of using the same can easily suppress disuse muscle atrophy based on, for example, injury, illness, aging, lack of exercise, and the like. The method for using a muscle atrophy inhibitor is to mix a muscle atrophy inhibitor into a space food, for example, to easily suppress disuse muscle atrophy of a space resident under weightless conditions. This can contribute to longer time.

  The prenylated flavanone contained in the muscle atrophy inhibitor is sparingly water-soluble, and therefore when absorbed as it is, there is a possibility that sufficient absorption in the body cannot be obtained. In addition, when a muscle atrophy inhibitor is ingested with water, prenylated flavanone is poorly water-soluble, so that it may remain in the oral cavity or cause stickiness in the oral cavity, which may cause discomfort during ingestion. . In this regard, according to the method of using the muscle atrophy inhibitor, the muscle atrophy inhibitor is mixed with food and drink and ingested. For example, by dispersing in a drink or mixing with food or drink, It becomes easy to increase the absorption rate of the prenylated flavanone or to reduce the uncomfortable feeling when taking the muscle atrophy inhibitor.

The effects exhibited by this embodiment will be described below.
(1) A muscle atrophy inhibitor that suppresses disuse muscle atrophy is provided by containing prenylated flavanone as an active ingredient.

  (2) When the prenylated flavanone contains at least one of prenylated naringenin and prenylated eriodictyol, for example, the grasshopper can be used effectively.

(3) The prenylated flavanone is preferably derived from a plantain extract. In this case, the grasshopper can be used effectively.
(4) It becomes easy to raise the density | concentration of a prenylated eriodictyol by using what was obtained by extracting from a fruit as a plantain extract.

  (5) According to the method of using a muscle atrophy inhibitor that is incorporated into a food or drink and ingesting a muscle atrophy inhibitor, the absorption rate of prenylated flavanone in the body is increased, or the sense of incongruity when the muscle atrophy inhibitor is ingested is increased. It becomes easy to reduce.

In addition, the said embodiment can also be changed as follows.
-A muscular atrophy inhibitor and its method of use are not limited to application to humans, and may be applied to animals such as horses, cows, dogs, and cats.

-You may implement the said usage method together with exercise training, rehabilitation, and a general diet, for example.
The muscular atrophy inhibitor and the method for using the same may be applied to the prevention of the progression of disused muscular atrophy in addition to the prevention of disuse muscular atrophy.

Next, the embodiment will be specifically described with reference to examples and comparative examples.
Example 1
A test was conducted in which mice were fed a diet supplemented with prenylated flavanones. As the prenylated flavanone, 8-prenylnaringenin (hereinafter referred to as prenylated naringenin) was used. Prenylated naringenin is artificially chemically synthesized with a purity of 95% or more in the National University Corporation Tokushima University Graduate School, Health Bioscience Research Department, Functional Molecular Synthetic Pharmacy.

  Preparation of feed by adding prenylated naringenin to the standard purified feed AIN-93M (standard purified feed for nutritional studies using mice and rats published in 1993 by the National Institute of Nutrition (AIN)) did. The amount of prenylated naringenin added was an amount (calculated as a purity of 95%) containing 100 mmol of prenylated naringenin (molecular weight 340.37) in flavanone equivalent in 100 g of standard purified feed. That is, it added so that 0.2 g of prenylated naringenin (purity 95% or more) might be contained in 100 g of standard refined feed. The standard purified feed to which prenylated naringenin was added was adjusted in composition with the standard purified feed as a control by reducing the amount of cellulose in advance.

  A feed supplemented with prenylated naringenin and a control feed were administered to 4 C57BL / 6 mice (7 weeks old, male, purchased from Japan SLC) in each of the administration group and the control group. Gave. For drinking water, tap water was used freely. The mice in each group were divided into groups after one week of preliminary breeding.

After feeding for 18 days, disuse muscular atrophy was induced by performing an operation to remove the sciatic nerve in the right hind leg of the mouse. The left hind limb was used as a control by performing a sham operation on the left hind limb.
For 4 days after the operation, the mice were fed with food in the same manner as described above, and tap water was freely taken. Four days after the operation, the gastrocnemius of the left and right hind limbs of the mouse was removed, and the weight of the gastrocnemius was measured.

  By calculating the weight of the gastrocnemius muscle of the right limb when calculating the weight of the gastrocnemius muscle of the right limb when the weight of the gastrocnemius muscle of the left limb is calculated as 100%, Asked.

(Comparative Example 1)
In place of prenylated naringenin, naringenin (manufactured by Tokyo Kasei Kogyo Co., Ltd., purity 90%) was used to conduct a test in which feed was given to mice in the same manner as in Example 1. The feed was prepared by adding naringenin to the standard purified feed AIN-93M. The amount of naringenin added was such that 100 g of standard purified feed contained 5.6 mmol of naringenin (molecular weight 270.5) in terms of flavanone equivalent. That is, it added so that 0.17g of naringenin (purity 90%) might be contained in 100g of standard refined feed. The standard purified feed to which naringenin was added was combined with the control feed by reducing the amount of cellulose in advance.

(Results of Example 1 and Comparative Example 1)
The percentage of muscle atrophy in the control group was 90.3%. In contrast, the percentage of muscle atrophy in the naringenin diet group was 92.9%, and the prenylated naringenin diet group was 102.1%. These results are shown in FIG. And as a result of performing statistical processing about the result of each group using the Tukey method, there was a significant difference between the prenylated naringenin diet group and the other groups. Therefore, prenylated naringenin was found to suppress disuse muscle atrophy. Moreover, since naringenin does not show the inhibitory effect of disuse muscle atrophy, it was found that the inhibitory effect is obtained based on prenylation.

  Next, Table 1 shows the body weight and food intake when the gastrocnemius muscle was removed.

As shown in Table 1, it was found that the group given prenylated naringenin was lower than the other groups in terms of body weight and food intake. Furthermore, it shows in FIG. 2 about the change of the food intake during a test period. For about one week from the start of the experiment, although a difference in food intake was observed in each group, the food intake was almost the same between the groups thereafter. Note that the prenylated naringenin diet group had lower food intake than the other groups, indicating that the prenylated naringenin diet group had less food intake than the other groups at the beginning of the study period. It can be seen that this is due to this. In this regard, as the amount of food intake becomes stable and comparable to that of the other groups over the course of the test period, it is considered that the weight of the gastrocnemius muscle is not significantly affected. Moreover, since the effect is confirmed by the ratio of the weight of the atrophic muscle to the normal muscle in the same individual, it is considered that there is no influence of the body weight.

  That is, there is no significant difference in flavanone intake (mmol / animal / day) between the prenylated naringenin diet group and the naringenin diet group, and there is no effect on gastrocnemius muscle weight due to the difference in feed intake. The inhibitory effect is thought to be due to the action of prenylated naringenin.

(Example 3)
In Kunigami-gun, Okinawa Prefecture, we used fruits of Macaranga tanarius collected in June 2009 and stored frozen. 1 kg of this fruit was immersed in 3 L of ethanol for 24 hours. The filtrate was obtained by filtering the soaked material using diatomaceous earth as a filter medium, and then the filtrate was concentrated with an evaporator to obtain a concentrated solution. Next, the concentrated liquid was fractionated using a preparative ODS column to obtain a fraction liquid containing a large amount of prenylated flavanone. The obtained fraction solution was concentrated with an evaporator, and ethanol and water were removed to obtain a viscous oily extract.

  As a result of analyzing the components contained in the obtained oily extract by high performance liquid chromatography, it contained about 80 w / w% of prenylated flavanone. The compound name and content of prenylated flavanone are shown in Table 2.

Next, the test which gives a mouse | mouth the feed which added the obtained extract was done.

  The feed was prepared by adding the extract to the standard purified feed AIN-93M (standard purified feed for nutritional studies using mice and rats published in 1993 by the National Institute of Nutrition (AIN)). . The amount of the extract added was such that the concentration of the extract in the feed added so that 0.2 g of extract was contained in 100 g of the standard purified feed was 0.2 w / w%. In addition, the said standard refined feed to which an extract was added adjusted the composition with the said standard refined feed used as a control | contrast by reducing the quantity of a cellulose beforehand.

  Feed containing the extract and the above-mentioned standard purified feed as a control were supplied to 5 C57BL / 6 mice (7 weeks old, male, purchased from Japan SLC) for 2 weeks each in the group of the grasshopper group and the control group for 2 weeks. Ad libitum. For drinking water, tap water was used freely.

After free feeding for 2 weeks, disuse muscular atrophy was induced by performing an operation to remove the sciatic nerve in the right hind leg of the mouse. The left hind limb was used as a control by performing a sham operation on the left hind limb.
For 4 days after the operation, the mice were fed with food in the same manner as described above, and tap water was freely taken. Four days after the operation, the gastrocnemius of the left and right hind limbs of the mouse was removed, and the weight of the gastrocnemius was measured.

  By calculating the weight of the gastrocnemius muscle of the right limb when calculating the weight of the gastrocnemius muscle of the right limb when the weight of the gastrocnemius muscle of the left limb is calculated as 100%, Asked.

(Result of Example 3)
In Table 3 and FIG. 3, the result about the weight ratio (%) of the atrophied muscle with respect to the normal muscle in each group is shown.

As a result of performing a t-test on this result, there was a significant difference between the weevil diet group and the control group. Thereby, it turns out that the grasshopper extract containing prenylated flavanone can suppress disuse muscle atrophy.

Claims (3)

It is a disuse muscular atrophy inhibitor for use in obtaining a food / beverage product composition for inhibiting disuse muscle atrophy by blending in a food / beverage product,
It contains at least one of a grasshopper extract and 8-prenylnaringenin as an active ingredient, and the leafhopper extract contains nymphaeol-A, nymphaeol-B, isonympheol-B, nymphaeol-C, and 3'-geranylnaringenin. A disuse muscular atrophy inhibitor characterized by containing.   A food / beverage composition for inhibiting disuse muscle atrophy, comprising the agent for inhibiting disuse muscle atrophy according to claim 1.   A food extract containing at least one active ingredient of Nympheol-A, Nimpheol-B, Isonymfeol-B, Nimpheol-C, and 3′-geranylnaringenin, and 8-prenylnaringenin. The manufacturing method of the food-drinks composition for disuse muscular atrophy characterized by this.