JP5884112B2 - Muscle enhancer - Google Patents

Description

  The present invention relates to a muscle enhancer that can safely increase muscle mass.

  There are many cases where walking is difficult due to aging, lack of exercise, or inability to exercise. In addition, wrinkles that occur due to a decrease in muscle mass are cosmetic problems, and no solution is known.

  After the war, Japan was able to join the world's longevity countries due to changes in the living environment and meal content. However, care and medical care are attracting attention as a social problem that stems from a decline in mental and physical activities of the elderly. Everyone wants to be healthy until they reach the age of life, and to have a life with a short final bed period without suffering from lifestyle-related diseases.

  The greatest characteristic of aging in humans, which are multicellular organisms, is first a decrease in the number of cells and a decrease in cell function. When walking becomes difficult due to circulatory diseases such as the brain and heart, atrophy of the fallen muscle is induced, and QOL (Quality of Life) is further deteriorated.

  Even if it does not go so far, wrinkles and talmi due to atrophy of arms, neck, face and other muscles with aging are familiar problems. However, there is no practical synthetic drug that suppresses muscle atrophy or specifically supports the increase in muscle.

  Conventionally, steroid hormones are well known as compounds for strengthening muscles. However, it is also known that serious side effects such as cardiovascular diseases occur in athletes who have taken steroid hormones for the purpose of muscle strengthening.

  On the other hand, a safe muscle enhancer is also being sought. For example, Patent Document 1 includes an apple-derived polyphenol as an active ingredient, which prevents the transition from a slow-muscle type I to a fast-muscle type II due to disuse muscle atrophy, A preparation that suppresses muscle atrophy and at the same time promotes the recovery of muscle mass at the time of recovery of a contracted muscle is disclosed.

JP 2006-328031 A

  As described above, a safe muscle enhancer different from steroid hormones has been sought, and the technique of Patent Document 1 using an apple-derived polyphenol for recovery of muscle mass is also known.

  However, the technique of Patent Document 1 is a technique for suppressing the type transition of a muscle that has been atrophied due to disuse muscle atrophy or increasing the amount of muscle, for example, increasing the amount of muscle in a healthy person, It is unclear whether it will be effective. Actually, the experimental data described in Patent Document 1 is only from a model animal in which muscle atrophy is caused by hanging the hind limb of a rat.

  Under the circumstances described above, the present invention provides a muscle strengthening agent that is safe and can not only recover muscle mass once reduced by atrophy, but also increase muscle mass in general humans and other animals. The purpose is to do.

  This inventor repeated earnest research in order to solve the said subject. For example, we use natural powders known to be useful for preventing aging and so-called tonic medicines, such as sanshuyu fruit, jujube fruit, rat peach fruit, Sadako and commercial dried fruit. Animal experiments were conducted in addition to the feed, but no good results were obtained. In particular, apple fruit press residue alone was insufficient to increase the muscle mass of healthy laboratory animals. However, the present inventors have found that the muscle mass of healthy individuals and healthy laboratory animals can be significantly increased if rosemary extract is used in combination with apple fruit press residue, and the present invention has been completed.

  The muscle strengthening agent which concerns on this invention contains an apple fruit pressing residue and a rosemary extract, It is characterized by the above-mentioned.

  In the muscle strengthening agent of the present invention, the mass ratio of apple fruit press residue to rosemary extract is preferably 5 times or more and 15 times or less. The effect of the muscle strengthening agent containing apple fruit press residue and rosemary extract in such a ratio has been confirmed by the experimental knowledge of the present inventors.

As the rosemary extract which is one of the active ingredients of the muscle enhancing agent according to the present invention, those derived from rosemary leaves and those extracted using C _1-4 alcohol as an extraction solvent are preferable. . The effect of the muscle-enhancing agent of the present invention containing such a rosemary extract has been confirmed by the inventor's experimental findings.

  The dosage of the muscle enhancing agent according to the present invention is preferably 50 mg / kg body weight or more and 200 mg / kg body weight or less per day. According to experiments on healthy humans, a clear increase in muscle mass was observed at doses in this range.

  The muscle-strengthening agent according to the present invention contains apples that are also edible and rosemary extract that is also edible as herbal teas and spices as an active ingredient. Suitable and extremely safe. The muscle enhancer according to the present invention can increase the muscle mass of not only patients with muscle atrophy such as bedridden patients due to illness or aging, but also healthy humans and other animals. Furthermore, it is possible to improve wrinkles and tarmi caused by a decrease in muscle mass. Therefore, the muscle strengthening agent according to the present invention is extremely useful industrially as a very practical one.

FIG. 1 is a graph showing changes in the total intake and body weight of feed and water in a muscle enhancement test using mice. (1) is the total intake of water, (2) is the total intake of feed, and (3) is the change in body weight. FIG. 2 is a graph showing the mass of each organ in a muscle enhancement test using mice. (1) shows heart mass, (2) shows liver mass, (3) shows kidney mass, and (4) shows lung mass. FIG. 3 is a graph showing the mass of each organ in a muscle enhancement test using mice. (1) shows the mass of the spleen and (2) shows the mass of the testicle. FIG. 4 is a graph showing the amount of fat around the testicles in a muscle enhancement test using mice. “*” In FIG. 4 indicates a case where a significant difference is recognized at p <0.05 by the t difference test. FIG. 5 is a graph showing the muscle mass of the hind limbs in a muscle enhancement test using mice. “*” In FIG. 5 indicates a case where a significant difference is recognized at p <0.05 by the t difference test. FIG. 6 is a graph showing changes in leg muscle mass scores in a muscle enhancement test for humans. (1) shows the change in leg muscle mass score of the control group taking inulin, which is a general water-soluble dietary fiber, and (2) is the leg muscle mass of the group taking the muscle strengthening agent according to the present invention. Shows the change in score.

  The muscle strengthening agent according to the present invention is characterized by containing apple fruit press residue and rosemary extract as active ingredients.

  Although the apple which is a raw material of the apple fruit press residue which is one of the active ingredients of the muscle strengthening agent which concerns on this invention is not restrict | limited, For example, the western apple (Malus pumilla) more generally attached | subjected to edible is used. Not only fruit but also Japanese apple (Malus asiatica) fruit can be used. Moreover, the form of the apple fruit to be used is not particularly limited. For example, the apple fruit can be used as it is with the river, or the river from which the river has been removed, or the river and the core have been removed.

  In the present invention, the “apple fruit pressing residue” refers to a remaining residue obtained by squeezing an apple to remove fruit juice. For example, a remaining residue obtained by manufacturing apple juice can be used. Its main component is insoluble dietary fiber. “Dietary fiber” is an indigestible or indigestible component that is contained in food and is not degraded by human digestive enzymes. It mainly consists of plant food and the cell walls of fungal plants. It consists of sugars. In addition, apple fruit pressing residue is a product name of apple fiber or apple fiber, and is sometimes marketed as a dried product.

  The apple fruit pressing residue in the present invention may be any remaining residue obtained by pressing the apple and removing the fruit juice, and includes, for example, moisture, protein, lipid, mineral, and sugar in addition to dietary fiber derived from apple. Also good. Moreover, since it is difficult to remove fruit juice completely, a part of fruit juice and its dried product may remain in the apple fruit pressing residue used by this invention. The apple fruit press residue of this invention should just contain the dietary fiber component in the range by which the increase effect of muscle mass is exhibited, Specifically, it is preferable that the dietary fiber contains 20 mass% or more. As the said ratio, 25 mass% or more is more preferable, and 30 mass% or more is further more preferable. On the other hand, the upper limit of the ratio is not particularly limited, and may be 100% by mass, but it may be technically difficult to separate only dietary fiber from the raw material apple fruit, and the production cost may be excessive, Since components other than dietary fiber may contribute to the exertion of muscle strengthening action, the proportion is preferably 90% by mass or less, more preferably 80% by mass or less, further preferably 70% by mass or less, 60 mass% or less is more preferable, and 50 mass% or less is further more preferable.

  Although the manufacturing method in particular of apple fruit pressing residue is not restrict | limited, For example, the residue which pressed apple fruit for manufacture of apple juice etc. can be used. Furthermore, you may use the said residue dried and water content made 4 mass% or more and 10 mass% or less. The water content can be measured by, for example, a normal pressure heating drying method.

  Rosemary (Rosmarinus officinalis, Lamiaceae) is a small evergreen shrub that is well known as a spice raw material with a thick aromatic leaf and a height of about 2 m. Originated in the Mediterranean region, it is cultivated all over the world, including the United States, England, France and Spain. As components contained in rosemary, many components such as phenolic compounds and triterpenoid compounds are known in addition to fats and oils and flavonoids. In addition, the action of the extract on the bile duct and small intestine and the blood flow increasing action of the coronary arteries have been reported. In European phytotherapy, rosemary leaves are also used for indigestion, rheumatism, and cardiovascular diseases. It is also used as a bath agent. In food, it is used in many fields, including alcoholic beverages, baked confectionery, frozen dairy products, meat and meat product seasonings, condiments, processed vegetables, snacks, and gravy. It is also a medicinal herb that is used as a herbal tea in anticipation of a healthy stomach effect. In China, leaf and branch extracts are also used for headaches.

  As a raw material part of the rosemary extract, leaves and / or branches are preferable, and leaves are more preferable. In addition, since rosemary contains a fragrant oil and fat component, directly using rosemary leaves or the like as a raw material may result in a strong fragrance of the resulting extract that is difficult to take. Therefore, you may use the residue after removing fats and oils components, such as the residue after manufacturing rosemary oil, by steam distillation.

As the extraction solvent, a water-soluble organic solvent and a mixed solvent of water and a water-soluble organic solvent are preferable. The water-soluble organic solvent is not particularly limited, and may be appropriately selected from those that can provide a rosemary extract capable of exerting an excellent muscle-enhancing effect in combination with apple crush residue, for example, methanol, ethanol, 1 -C _1-4 alcohols of propanol, 2-propanol, n-butanol, isobutanol, s-butanol, t-butanol; water-soluble ether solvents such as diethyl ether and tetrahydrofuran; water-soluble amides such as dimethylformamide and dimethylacetamide Examples of the solvent include water-soluble sulfoxide solvents such as dimethyl sulfoxide. Among these, C _1-4 alcohol is preferable from the viewpoint of safety and the like, C _1-2 alcohol is more preferable, and ethanol is more preferable.

  When a mixed solvent of water and a water-soluble organic solvent is used, the concentration of the water-soluble organic solvent with respect to the whole may be adjusted as appropriate. For example, it can be 50 v / v% or more, preferably 60 v / v% or more. 70 v / v% or more is more preferable, 80 v / v% or more is further preferable, and 90 v / v% or more is particularly preferable. The upper limit is not particularly limited, but can be, for example, 99 v / v% or less.

  The amount of the extraction solvent used is not particularly limited and may be adjusted as appropriate. For example, it can be about 2 mass times or more and 20 mass times or less with respect to rosemary. The ratio is preferably 5 times or more, more preferably 7 times or more, more preferably 15 times or less, and more preferably 12 times or less.

  The extraction temperature can also be adjusted as appropriate, and can be, for example, 10 ° C. or higher and 80 ° C. or lower. In addition, when extracting above the boiling point of a solvent, it is preferable to seal or pressurize an extraction container. Further, the extraction solvent may be heated to reflux. Further, the extraction temperature may be changed in stages.

  The extraction time can also be adjusted as appropriate. For example, the extraction time can be about 1 hour or more and 50 hours or less in total.

  The extracted liquid mixture can be used as it is, but normal post-treatment may be performed. For example, the extraction residue and the extraction solvent may be separated by filtration or centrifugation, or the separated extract may be dried by appropriately combining heating drying, reduced pressure drying, freeze drying, and the like. In addition, when drying by heating, it is preferable to concentrate at 60 ° C. or less, preferably 50 ° C. or less, while reducing the pressure, so that the active ingredient does not decompose.

  The obtained rosemary extract may be partially purified mainly to remove the fat and oil component, particularly when extraction is performed without removing the fat and oil component. For example, if the extract is concentrated or an insoluble component that precipitates by adding a poor solvent to the extract is filtered and washed, the main oil component can be removed because it is liquid at room temperature.

  The ratio of apple fruit press residue and rosemary extract in the present invention may be appropriately adjusted within the range in which the effect of increasing muscle mass is exerted, for example, the mass ratio of apple fruit press residue to rosemary extract It can be 5 times or more and 15 times or less. The mass ratio is preferably 6 times or more, more preferably 7 times or more, further preferably 8 times or more, further preferably 14 times or less, more preferably 13 times or less, and further preferably 12 times or less. In addition, since the said mass ratio changes with the drying degree of an apple fruit press residue or a rosemary extract, after adjusting the water content of an apple fruit press residue and a rosemary extract to 5 mass% or more and 6 mass% or less It shall be calculated by

  The dosage form of the muscle strengthening agent according to the present invention is not particularly limited. For example, the apple fruit press residue and the dried rosemary extract may be simply mixed, or the apple fruit press residue and rosemary extract may be dispersed or dissolved in water. . In addition, rosemary leaves may be used as bathing agents, and rosemary-derived essential oils and extracts may be used as perfumes for external preparations, soaps, cosmetics, etc. Such a muscle strengthening agent is highly effective when orally administered, and is preferably an oral agent from the viewpoint of ease of ingestion and administration.

  Although it does not restrict | limit especially as an oral formulation, For example, a tablet, a powder, a capsule, a sugar-coated tablet, a granule etc. can be mentioned. For the muscle strengthening agent according to the present invention, a pharmaceutically acceptable additive may be used in accordance with the dosage form. Examples of such additives include excipients, bases, preservatives, auxiliaries, stabilizers, wetting agents, pH adjusting agents, antioxidants, colorants, sweeteners and the like. However, the dried apple fruit press residue and rosemary extract, which are the active ingredients of the muscle enhancer according to the present invention, can be granulated without adding excipients or the like. In addition, the suspension may be a beverage or may be added to a general diet.

  The muscle strengthening agent according to the present invention can be administered to animals other than humans in addition to humans. For example, it can also be used to increase the muscle mass of pets that have become difficult to exercise due to aging as in humans. However, it is preferably used for humans.

  The frequency and amount of administration of the muscle-enhancing agent according to the present invention are appropriately adjusted according to whether the improvement target is severe muscle loss or mere sputum or talmi, the patient's age, sex, condition, etc. do it. According to the experimental data described later, a significant muscle mass increasing effect was confirmed by administration of about 130 mg / day of dry body per body weight (kg) of human. From this result, for example, the dosage for humans is preferably about 50 mg / kg body weight or more and 200 mg / kg body weight or less per day in a dried apple fruit press residue-rosemary extract mixture. The number of administrations per day is preferably 1 or more and 5 or less, more preferably 1 or more and 3 or less.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited by the following examples, but may be appropriately modified within a range that can meet the purpose described above and below. Of course, it is possible to implement them, and they are all included in the technical scope of the present invention.

Example 1: Preparation of a muscle strengthening agent according to the present invention Pressed residue produced from squeezing fruit of Japanese apple (Malus asiatica) and Western apple (Malus pumila) to produce apple juice (from Akita New Bio Farm Co., Ltd.) Eiyo) was dried with warm air at 90 ° C. for 3 days under normal pressure, and the moisture content was adjusted to a range of 5 to 6% by mass to obtain apple fruit pressed residue.

  The composition analysis of the obtained apple fruit pressing residue was requested to the Japan Food Analysis Center. The results are shown in Table 1.

  As the above result, the obtained apple fruit press residue contained about 30% by mass of dietary fiber. Moreover, about 10-20 mass% of pectin was contained.

  In addition, a commercially available powdered rosemary extract (manufactured by Sabinsa Japan Corporation, product name “Rosemary extract”) as a health food material was purchased and used. The said extract is what was heated and extracted from the rosemary leaf using ethanol as a solvent, and the fat and oil component was removed.

  As a result of preliminary experiments using mice, when the food content and the amount of exercise were reared without any particular designation or restriction, a mixture of apple fruit compressed residue: rosemary extract mixing ratio of 10: 1 by mass ratio was obtained. It was recognized that the effect of increasing muscle mass was the most excellent. Therefore, the mixture which mixed the said apple fruit pressing residue and rosemary extract by 10: 1 (mass ratio) was used in the following experiment.

Example 2: Muscle enhancement effect test using experimental animals 2% by mass or 10% by mass of the above-mentioned apple fruit pressed residue-rosemary extract mixture is added to normal feed (product name “MF powder” manufactured by Oriental Yeast Co., Ltd.) And mixed. For comparison, a comparative feed was prepared by adding 10% by mass of the apple fruit press residue to the normal feed.

  20 male dd-Y mice weighing 20 to 22 g (obtained from Kiwa Laboratory Animal Research Co., Ltd.), 5 each arbitrarily, normal feed group (control group), sample 2% addition group, sample 10% addition group Divided into comparative feed groups, the normal feed, the same normal feed added with 2% by weight of the specimen, the same normal feed added with 10% by weight of the specimen, or the same normal feed and water added with only 10% by weight of apple fruit press residue And were allowed to eat freely. Each mouse was individually raised in a laboratory with a 12 hour light / dark cycle, a temperature of 22 ± 1 ° C., and a humidity of 55 to 65%. Five weeks after the start of the experiment, the mice were sacrificed, and the mass of each organ, the fat mass around the testicles, and the hindlimb muscle mass were measured. Changes in the total intake and body weight of feed and water are shown in FIG. 1, the mass of each organ is shown in FIGS. 2 and 3, the fat mass around the testicles is shown in FIG. 4, and the hindlimb muscle mass is shown in FIG.

  As shown in FIG. 1, no abnormal individuals were observed in the total intake of feed, total intake of water, and body weight, and significant differences were observed among the control group, the sample administration group, and the comparative feed administration group. There wasn't.

  As for the mass of each organ, as shown in FIGS. 2 and 3, no particularly abnormal individuals were observed, and no significant difference was observed among the control group, the sample administration group, and the comparative feed administration group. In addition, assuming that the lifespan of mice is 3 years and the lifespan of humans is 90 years and the continuous administration over 5 weeks is applied to humans, the muscle potentiator according to the present invention is at least 150 weeks (about 2.8 years). ) It is presumed that it is safe without causing any abnormality even if ingested.

  As shown in FIG. 4, the amount of fat around the testicle was clearly reduced in the group administered with the muscle-enhancing agent according to the present invention compared to the control group. In particular, in the group fed with 10% by weight of the muscle-enhancing agent according to the present invention, a significant difference from the control group was found at p <0.05 by the significant difference test by the t test, and the average fat amount was the control. There was a 42% decrease compared to the group.

  As for the hind limb muscle mass, as shown in FIG. 5, in the group fed with 10% by mass of the muscle-enhancing agent according to the present invention, p <0.05 in the significant difference test by the t test and significant for the control group. Muscle strengthening effect was observed. On the other hand, in the group which ingested the feed which added only the apple fruit pressing residue, the muscle reinforcement | strengthening effect was not recognized even if the addition ratio was 10 mass%.

  As described above, when the muscle-enhancing agent according to the present invention was administered, the body weight compared to the control group ingested only the normal feed and the comparative feed administration group ingested the feed containing only the apple fruit compressed residue While no difference was observed, fat mass was reduced and muscle mass increased. From these results, it is considered that the muscle enhancer according to the present invention promotes the expression of genes that increase the muscle mass by changing the metabolic pathway of accumulated fat.

Example 3 Muscle Strengthening Action Test on Human Next, the presence or absence of muscle strengthening action was examined in human experiments. 5 subjects (2 men and 3 women) aged 56 to 78 years were given 2 g of a mixture of apple fruit pressing residue: rosemary extract = 10: 1 (mass ratio) as in Example 1 above. 3 times before meals. Further, as a control, another 48-72 year-old subject (1 male, 4 female) was similarly given inulin, which is a typical water-soluble dietary fiber. During the test period, the subject did not have any special exercise, and had the same life as before the start of the test without changing the food contents except for the above-mentioned use. At the start of the test and 2 months later, the leg muscle mass score was measured using a dual frequency body composition meter (Tanita, DC-320). FIG. 6 shows changes in leg muscle mass scores at the start of the test and after 2 months in the control group and the group taking the muscle strengthening agent according to the present invention.

  As shown in the results of FIG. 6, it was experimentally proved that there is a tendency to increase muscle mass even in humans with the muscle-enhancing agent according to the present invention without depending on a special meal or exercise.

Claims (6)

  A muscle strengthening agent characterized by containing apple fruit press residue and rosemary extract.   The muscle strengthening agent according to claim 1, comprising apple fruit press residue of 5 times or more and 15 times or less by mass ratio to the rosemary extract.   The muscle strengthening agent according to claim 1 or 2, wherein the rosemary extract is derived from leaves of rosemary. The muscle enhancer according to any one of claims 1 to 3, wherein the rosemary extract is extracted using C _1-4 alcohol as an extraction solvent.   The muscle strengthening agent according to any one of claims 1 to 4, which is administered at a dose of 50 mg / kg body weight or more and 200 mg / kg body weight or less per day. Rosemary and C _1-4 Obtaining a rosemary extract by mixing alcohol; and
The manufacturing method of the muscle strengthening agent characterized by including the process of mixing a rosemary extract and apple fruit pressing residue.