JP6109909B2 - Muscle enhancer - Google Patents

Description

  The present invention relates to a muscle enhancer. Moreover, this invention relates to the foodstuff which has a muscle enhancement effect.

  It is known that muscle is effectively strengthened by increasing protein intake. For this reason, muscle strengthening agents containing various proteins have been studied. For example, beef extract has been reported to increase both slow and fast muscles. It has also been reported that beef extract has a property of changing fast muscles to slow muscle type muscle fibers. (Non-patent document 1).

  In addition, it has been reported that supplementing food with L-arginine increases both slow and fast muscles (Non-patent Document 2).

  Muscles are classified into fast muscle fibers (white muscle) that can instantaneously contract and slow muscle fibers (red muscle) that can continuously contract. The fast muscle can be quickly contracted and is used to extract the instantaneous force. The fast muscle is a muscle often used during anaerobic exercise, and it is also called a white muscle because of its color. Slow muscles are small muscles that are used to slowly contract and draw endurance. The slow muscle is a muscle often used during aerobic exercise, and it is also called red muscle because of its color. Since the muscles used differ depending on the type of exercise, a food that can specifically strengthen any type of muscle is desired. However, foods and drugs that can specifically enhance either fast or slow muscle are not known. In addition, no drug or food ingredient that can change the slow muscle into a fast muscle type muscle fiber has been reported.

  On the other hand, fish and shellfish-derived proteins are known to have various actions on living organisms, and many fish and shellfish-derived proteins have been studied for their effects on the organism. For example, it has been found that the intake of fish protein suppresses the accumulation of visceral fat (Patent Document 1). In addition, fish and shellfish-derived proteins are known to improve lipid metabolism. For example, it is described that fish and shellfish-derived proteins have a blood cholesterol lowering effect (Patent Document 2). In addition, fish-derived proteins have been studied for their effects in the living body. For example, walleye pollack-derived protein has been reported to have an effect on cholesterol and triglycerol (Non-patent Document 3), and in rats fed with walleye pollen-derived protein, plasma was compared with rats fed casein. It has been shown that the concentration of triglycerol in the medium decreases and the concentration of cholesteryl ester in the liver increases.

International Publication No. 2007/069716 JP 2010-95456 JP

Hiroyuki Yoshihara et al., “Beef Extract Supplementation Increase Leg Muscle Mass and Modifies Skeletal Muscle Fiber Types in Rats”, J Nutr Sci Vitaminol, 2006, 52, p.183-193 Wenjuan Jobgen et al., “Dietary L-Arginine Supplementation Reduces White Fat Gain and Enhances Skeletal Muscle and Brown Fat Masses in Diet-Induced Obese Rats”, The Journal of Nutrition, 2009, 139, p.230-237. Anjali Shukla et al., “Dietary fish protein alters blood lipid concentrations and hepatic genes involved in cholesterol homeostasis in the rat model”, British Journal of Nutrition, 2006, 96, p.674-682

  An object of this invention is to provide the muscle strengthening agent containing the fish meat protein of the fish which belongs to the order of Cod. Another object of the present invention is to provide a food having muscle strengthening action.

  The present inventors paid attention to the effect of walleye pollock fish meat protein on the physiological action and, as a result of repeated research, found that walleye pollock fish meat protein has a muscle-enhancing action and arrived at the present invention.

  That is, the present invention provides a fast muscle-specific muscle enhancer containing fish protein of fish belonging to the order of Cod.

  The present invention also provides a muscle-enhancing agent that contains fish protein of fish belonging to the order of Codidae and changes the slow muscle to the fast muscle type.

  The present invention also includes a food protein containing fish protein of a fish belonging to the order of a cod, and a label indicating that it has a fast muscle-specific muscle-enhancing action or a label indicating that the slow muscle is changed to a fast muscle ( Functional food).

  The present invention also relates to a fish meat belonging to the order of a fish for producing a food with an indication that it has a fast muscle-specific muscle-enhancing effect or an indication that it has an action of changing a slow muscle to a fast muscle. Provide protein use.

  In addition, the present invention describes a food containing fish protein of a fish belonging to the order of the cod, that the food has a muscle strengthening action specific to fast muscles or an action to change slow muscles to fast muscles. Provide products packaged with instructions.

  The muscle-enhancing agent of the present invention can strengthen muscles specifically for fast muscles. Moreover, the muscle strengthening agent of this invention can change a slow muscle to a fast muscle type.

  The muscle strengthening agent of the present invention is useful as a nutritional supplement drink or food for athletes who need instantaneous power. It is also useful as various drinks and various foods for preventing and / or improving muscle mass and muscle weakness (sarcopenia) associated with aging.

The figure which shows the scuffing muscle reinforcement | strengthening effect by walleye pollock fish protein. The figure which shows the weight change of the soleus muscle by walleye pollock fish meat protein. The figure which shows the weight change of the scissors muscle by walleye pollock fish protein and Hoki fish protein. The figure which shows the weight change of a long-knee extensor muscle by administration of walleye pollack fish protein and Hoki fish meat protein. The figure which shows the weight change of a soleus muscle by administration of walleye pollack fish protein and Hoki fish meat protein. The figure which shows the change of the expression level of Myh4 gene by administration of walleye pollock fish meat protein. The figure which shows the change of the expression level of the Myh7 gene by administration of walleye pollock fish meat protein. The figure which shows the change of the expression level of PGC1 (alpha) gene by administration of walleye pollack fish meat protein. The figure which shows the change of the expression level of GLUT4 gene by administration of walleye pollock fish protein. The figure which shows the blood glucose level change by administration of walleye pollack fish meat protein. The figure which shows the weight change of the calf muscle by walleye pollock fish meat protein, soybean protein, egg white protein, casein, and whey. The figure which shows the weight change of the long calf extensor muscle by administration of walleye pollack fish protein, soybean protein, egg white protein, casein, and whey. The figure which shows the weight change of the soleus muscle by administration of walleye pollack fish protein, soybean protein, egg white protein, casein, and whey.

  Hereinafter, the muscle enhancing agent of the present invention will be described. The muscle strengthening agent of the present invention contains fish protein of fish belonging to the order of Cod.

  In the present invention, the fish meat protein may be the fish meat itself, but it is also possible to use a protein obtained by removing lipids by degreasing treatment. As a degreasing method, a method such as boiling, steaming or baking, or a method such as extraction using ethanol or hexane can be used. For example, walleye pollack fish and Hoki fish meat processed in the following steps can be used as fish meat protein. The walleye pollock fish meat is cut into an appropriate size, the cut sample is frozen, and then freeze-dried in a freeze dryer. The freeze-dried sample is pulverized by a conventional method, and ethanol or the like is added thereto to elute the fat-soluble component. Next, by removing ethanol, walleye fish protein can be obtained. When lipid is removed by degreasing, the intake energy can be reduced.

  Fish meat protein can also be decomposed and used so that it can be easily absorbed. For example, it can be degraded using proteolytic enzymes such as papain, trypsin, pepsin, bromelain, ficin and alcalase protease.

  In the present invention, the fish meat used as a raw material is preferably white meat, and particularly fish protein of fish belonging to the order of the cod. Specifically, examples of fish belonging to the order of Codella include walleye pollock, southern bluefin, northern blue whiting, king clip, hake, madara and hoki.

  As used herein, muscle augmentation means increasing muscle mass. Muscles are classified into fast muscle fibers capable of instantaneous contraction (white muscles) and slow muscle fibers capable of continuous contraction (red muscles). The muscle-enhancing agent of the present invention is fast muscle-specific. To strengthen muscles. In the present specification, fast muscle-specific muscle enhancement means that the muscle mass of fast muscle is increased more than the total muscle mass increased when compared with various proteins. Therefore, even when muscle enhancement is specific to fast muscles, slow muscles are enhanced at the same time.

  Moreover, the muscle strengthening agent of this invention has the effect | action which changes a slow muscle to a fast muscle type. In this specification, changing the slow muscle to the fast muscle type means that when the ratio of the slow muscle and the ratio of the fast muscle are compared, the ratio of the slow muscle decreases and the ratio of the fast muscle increases. .

  The fast muscle-specific muscle-enhancing agent of the present invention and the muscle-enhancing agent that changes the slow muscle to the fast muscle type can be a composition containing an optional component in addition to the above components. For example, the fast muscle-specific muscle-enhancing agent of the present invention, when used as a medicament, has a pharmaceutical composition together with a pharmaceutically acceptable base, carrier, excipient, disintegrant, lubricant and coloring agent. Can be provided as a product. Examples of carriers and excipients used in the pharmaceutical composition include lactose, glucose, sucrose, mannitol, potato starch, corn starch, calcium carbonate, calcium phosphate, calcium sulfate and crystalline cellulose. Examples of the binder include starch, gelatin, syrup, tragacanth gum, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, hydroxypropylcellulose, methylcellulose, ethylcellulose and carboxymethylcellulose. Examples of the disintegrant include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, sodium alginate, sodium carboxymethyl cellulose, carboxymethyl cellulose calcium and the like. Examples of lubricants include magnesium stearate, hydrogenated vegetable oil, talc and macrogol. As the colorant, any colorant allowed to be added to a pharmaceutical product can be used. The pharmaceutical composition may be sucrose, gelatin, purified shellac, gelatin, glycerin, sorbitol, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, cellulose phthalate acetate, hydroxypropylmethylcellulose phthalate, methyl methacrylate as necessary. Further, it may be coated with one or more layers with a methacrylic acid polymer or the like. Moreover, you may add a pH adjuster, a buffering agent, a stabilizer, a solubilizer, etc. as needed.

  In addition, the pharmaceutical composition can be provided as a preparation in any form. For example, the pharmaceutical composition can be prepared as an orally administered preparation, such as a sugar-coated tablet, buccal tablet, coated tablet and chewable tablet, capsules including troches, pills, powders and soft capsules, granules, suspensions, emulsions and dry syrups. It can be a liquid such as syrup and elixir. In addition, the pharmaceutical composition can be administered intravenously, subcutaneously, intraperitoneally, intramuscularly, transdermally, nasally, pulmonarily, enterally, buccally, and transmucosally for parenteral administration. It can be a formulation for administration, such as administration. For example, it can be an injection, a transdermal absorption tape, an aerosol, a suppository and the like.

  The fast muscle-specific muscle potentiator of the present invention and the muscle enhancer that changes the slow muscle into a fast muscle type can be provided as food. That is, a food containing fish meat protein of a fish belonging to the order of Cod and having an action of enhancing muscles specific to fast muscles and an action of changing slow muscles to a fast muscle type is provided. In the present invention, food means all foods including beverages, and includes general foods including health foods such as supplements, as well as foods for specified health use and nutritional function foods stipulated in the Health Function Food System of the Consumer Affairs Agency. Including. For example, a functional food with an indication that it has a fast muscle-specific muscle-enhancing effect or an indication that it has an effect of changing the slow muscle to a fast muscle type is provided. For example, a food containing fish protein of fish belonging to the order of Cod can be provided as it is. Also, to provide foods that are added to other foods, mixed or applied, etc., as food materials that have fast muscle-specific muscle strengthening action and action to change slow muscle to fast muscle type Can do. In addition to food, it can also be provided as cosmetics and food.

  In addition, a food containing fish meat protein of a fish belonging to Codidae, together with instructions describing that the food has a fast muscle-specific muscle-enhancing action or an action that changes the slow muscle to a fast-muscle type It can be provided as a packaged product.

  In addition, in order to produce a food with an indication that it has a fast muscle-specific muscle-enhancing action or an action that changes the slow muscle to a fast-muscle type as described above, fish protein of fish belonging to the cod eye Can be used. Although it is not limited to the muscle strengthening agent of this invention, and a foodstuff, it can contain the quantity required in order to show | play a muscle enhancement action specific to a fast muscle. The muscle-enhancing agent of the present invention, as well as food, can contain fish protein of fish belonging to the order of cod, for example, 100 μg to 0.999 kg / kg, preferably 10 g to 900 g / kg. .

  In addition, the fish protein of the fish belonging to the order of Cod is not limited depending on conditions such as symptom degree, patient age, weight and health condition when administered to a patient as a medicine, but for adults, it is 100 μg to 10 g / kg / day, preferably 0.1 to 1 g / kg / day, can be administered orally or parenterally, divided into once or 2 to 4 times or more per day, and can be administered at appropriate intervals. In addition, the fish protein used in the present invention does not have a strong effect and side effects unlike pharmaceutical products, so there is no limit on the daily intake.

  Example 1 Muscle strengthening effect of the product of the present invention

  A frozen Alaskan walleye fillet (Unicy) was cut into a size of about 1 cm × 1 cm × 1 cm with a band saw (Akiyama Machine Co., Ltd., 600ST). The cut samples were arranged in one layer on a freeze-drying tray, and pre-freeze for 4 hours at −30 ° C. with a freeze dryer (manufactured by Tokyo Rika Kikai Co., Ltd., TF20-85ATNNN), followed by freeze-drying for 4 days and nights. The freeze-dried sample was lightly crushed by hand and pulverized with a pin mill (manufactured by Hadano Sangyo Co., Ltd., EM-1A). 99.5% ethanol (manufactured by Wako Pure Chemical Industries, Ltd., reagent grade) was added to the pulverized freeze-dried sample to elute the fat-soluble component. After air-drying for 1 week, residual ethanol was removed with a rotary evaporator (manufactured by Tokyo Rika Kikai Co., Ltd., N-21NS) to obtain a walleye fish protein. About 1.5 kg of walleye fish protein was obtained from 10 kg of frozen walleye fillet. The component composition of the resulting walleye fish protein is shown in Table 1.

  Five-week-old male SD rats (obtained from Shimizu Experimental Materials Co., Ltd.) were divided into walleye fish meat protein group and casein group, and freely fed with powdered feed having the composition shown in Table 2, respectively. In addition, this powdered feed is obtained by Oishi et al. (Yoshie Oishi et al., “Alaska pollack protein prevents the accumulation of visceral fat in rats fed a high fat diet”, J. Nutr. Sci. Vitaminol., 2009, 55, p. The same feed as described in .156-161) was used. The casein contained in the feed of the casein group was from New Zealand Dairy Board. One group consisted of 8 rats, and the rats were ingested for 4 consecutive weeks, then dissected and the tissue weight was measured. At this time, the rats were ingesting 15-30 g of food per day.

Results FIG. 1 shows the result of measuring the weight of the puffer muscle, which is a representative of the fast muscles. Compared to the casein group, the weight of the calf muscle, which is representative of fast muscle, increased significantly in the walleye fish protein group.

  On the other hand, the result of measuring the weight of the soleus, which is representative of the slow muscle, is shown in FIG. There was no difference in the weight of the soleus muscle, which is representative of the slow muscle, between the casein group and the kettlefish fish protein group.

  Therefore, it was shown that walleye pollock fish meat protein has a muscle strengthening action specific to fast muscles.

  Example 2 Muscle enhancement effect, muscle fiber type change and muscle metabolism change by long-term administration of the product of the present invention in rats

  The walleye pollen fish protein used was obtained by the same procedure as in Example 1. Hoki fish meat protein was obtained from frozen New Zealand Hoki fillet (Tully's Co., Ltd.) in the same manner as in Example 1. About 1.6 kg of hoki fish protein was obtained from 10 kg of frozen hoki fillet. The component composition of the obtained hoki fish protein is shown in Table 3.

  Five-week-old male SD rats (obtained from Shimizu Experimental Materials Co., Ltd.) were divided into walleye fish protein group, Hoki fish protein group, and casein group, and were fed freely with powdered feed having the composition shown in Table 4, respectively. The casein contained in the feed of the casein group was from New Zealand Dairy Board. One group consisted of 10 rats, and the rats were ingested for 8 weeks continuously, then dissected and the tissue weight was measured. At this time, the rats were ingesting 15-30 g of food per day.

  Total RNA was extracted from the longus and soleus muscles of rats of the walleye fish protein group and casein group, and the mRNA levels of Myh4, Myh7, PGC1α and GLUT4 were quantified by RT-PCR. At the same time, the amount of cyclophilin mRNA was quantified and used as an internal standard for comparison. Table 5 shows primer sequences of each gene used in the PCR reaction.

Results FIG. 3 and FIG. 4 show the results of measuring the weight of the puffer muscle and the long calf extensor which are representative of the fast muscle. Compared to the casein group, the walleye pollack fish protein group and the hoki fish protein group significantly increased the weight of the puffer muscle and the long calf extensor muscle, which are representative of the fast muscle.

  On the other hand, the result of measuring the weight of the soleus, which is representative of the slow muscle, is shown in FIG. Compared with the casein group, in the walleye fish protein group and the hoki fish protein group, the weight of the soleus muscle, which is representative of the slow muscle, tended to increase, but no significant difference was observed.

  Therefore, it was shown that walleye pollack fish protein and hoki fish meat protein have fast muscle-specific muscle-enhancing effects by long-term administration.

  FIG. 6 shows the measurement results of the Myh4 gene, which is an index of fast muscle fibers. The expression level of the Myh4 gene was significantly increased in the walleye fish protein group compared to the casein group in the long-knee extensor muscle, which is a representative muscle of the fast muscle. On the other hand, in the soleus muscle, which is the representative muscle of the slow muscle, there was no difference in Myh4 gene expression between the two groups.

  Therefore, it was inferred that walleye pollack fish meat protein changes the muscle fiber type in a direction to make fast muscles faster.

  FIG. 7 shows the measurement results of the Myh7 gene, which is an indicator of slow muscle fibers. The expression level of the Myh7 gene was significantly decreased in the walleye fish protein group in the soleus muscle compared with the casein group. On the other hand, in the longus extensor, there was no difference in Myh7 gene expression between the two groups.

  Therefore, it was speculated that walleye fish protein changes the muscle fiber type in the direction of decreasing slow muscle fibers.

  FIG. 8 shows the measurement results of the PGC1α gene, which is an index of hyperlipid metabolism. The expression level of PGC1α gene was significantly decreased in the walleye fish protein group in the soleus muscle compared with the casein group. On the other hand, there was no difference in the expression of PGC1α gene between the two groups in the longus extensor muscle.

  In addition, FIG. 9 shows the measurement results of the GLUT4 gene, which is an indicator of increased carbohydrate metabolism. The expression level of the GLUT4 gene was significantly increased in the walleye fish protein group in the soleus muscle compared with the casein group. On the other hand, in the longus extensor, there was no difference in GLUT4 gene expression between the two groups.

  From the above results, it is inferred that carbohydrate metabolism is enhanced in the walleye fish protein group. In general, slow muscle consumes mainly lipids and fast muscle mainly consumes carbohydrates, so walleye fish protein can change soleus muscle from slow to fast muscle metabolism. Indicated. Considering the changes in the Myh7 gene, it was speculated that walleye fish protein changes the muscle fiber type in the direction that makes the slow muscle faster.

  Example 3 Inhibition of blood glucose level increase by long-term administration in rats

  Five-week-old male SD rats (obtained from Shimizu Experimental Materials Co., Ltd.) were divided into walleye fish meat protein group and casein group, and each was freely fed a powdered feed having the same composition as in Table 4. The casein contained in the feed of the casein group was from New Zealand Dairy Board. One group consisted of 12 rats, and the rats were ingested for 5 consecutive weeks. After fasting for 10 hours from the day before the test, a 40% glucose solution was administered at a rate of 200 mg per 100 g body weight. Blood was collected from the tail vein at each time point before administration, 30 minutes, 60 minutes, 90 minutes, and 120 minutes after administration. The collected blood was absorbed into a blood sugar level measuring chip (Life Scan, One Touch Ultra) and analyzed with a blood sugar analyzer (Roche, ACCU-CHEK Active glucose meter). At this time, the rats were ingesting 15-30 g of food per day.

Results FIG. 10 shows the results of changes in blood glucose level by the glucose tolerance test. Compared with the casein group, the increase in blood glucose level was significantly suppressed in the walleye fish protein group. Also in the comparison of the integral value for 120 minutes, it was confirmed that the increase in blood sugar level was significantly suppressed in the walleye fish protein group compared with the casein group.

  Therefore, it was demonstrated that walleye fish protein has an action of suppressing an increase in blood glucose level. It is inferred that the long-term administration of walleye pollock fish protein changed the muscle fiber type in the direction that the slow muscles become faster, and increased the utilization of carbohydrates in the muscles, resulting in a decrease in blood glucose level.

  Example 4 Comparison with other proteins of muscle enhancement by long-term administration of the product of the present invention in rats

  5-week-old male SD rats (obtained from Shimizu Experimental Materials Co., Ltd.) were divided into walleye fish protein group, soy protein group, egg white protein group, casein group, and whey group. Ad libitum. As a soy protein contained in the soy protein group feed, a product of Fuji Oil Co., Ltd. was used. The egg white protein contained in the feed of the egg white protein group was a product of Daiichi Kasei Co., Ltd. The whey contained in the whey group feed was Daiichi Kasei Corporation. Casein contained in the casein group feed was from New Zealand Dairy Board. One group consisted of 10 rats, and the rats were ingested for 8 weeks continuously, then dissected and the tissue weight was measured. At this time, the rats were ingesting 15-30 g of food per day.

Results FIG. 11 and FIG. 12 show the results of measuring the weight of the puffer muscle and the long ankle extensor, which are representative of the fast muscles. Compared with the casein group, the walleye fish protein group significantly increased the weights of the gluteal and long-knee extensor muscles, which are representative of the fast muscles. In addition, in the walleye fish protein group, the weight of the long rib extensor was significantly increased compared to the whey group. Compared to the soy protein group and the egg white protein group, the walleye fish protein group showed a tendency to increase the weight of the puffer muscle and the long extensor muscle, but no significant difference was observed.

  On the other hand, the result of measuring the weight of the soleus, which is representative of the slow muscle, is shown in FIG. Compared to the whey group, the walleye fish protein group significantly increased the weight of the soleus muscle, which is representative of the slow muscle. Compared with the soy protein group, egg white protein group, and casein group, the walleye fish protein group tended to increase the weight of the soleus muscle, but no significant difference was observed.

  Therefore, it was shown that walleye pollack fish meat protein has a stronger muscle-enhancing action than soybean protein, egg white protein, casein, and whey proteins after long-term administration.

Claims (4)

  A fast muscle-specific food composition for muscle enhancement, comprising fish protein of a fish belonging to the order of Cod or a proteolytic enzyme degradation product of said fish protein.   A food composition for enhancing muscles, which comprises fish protein of a fish belonging to the order of Cod or a proteolytic enzyme degradation product of the fish protein, wherein the slow muscle is changed to a fast muscle type. Claim 1 or containing a second food composition, fast twitch specific muscle potentiation muscle-building food marked with indication that alter the fast twitch display or slow-twitch indicating with. A package containing the food composition comprising the food composition of claim 1 or 2 together with instructions describing that the food has a fast muscle-specific muscle-enhancing action or an action that changes the slow muscle to a fast muscle. Products for strengthening muscles .