JP2014062068A - Preventive or therapeutic agent of disuse muscle atrophy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a preventive or therapeutic agent of disuse muscle atrophy, which comprises amino acid and has excellent effect.SOLUTION: A preventive or therapeutic agent of disuse muscle atrophy contains an animal protein or a decomposition product thereof, and comprises 250 mg or more of arginine, 260 mg or more of alanine, 470 mg or more of aspartic acid and 130 mg or more of glycine, relative to 1 g of total nitrogen. The animal protein preferably comprises a fish protein and the fish protein preferably comprises a fish protein of a fish belonging to Gadiformes.

Description

  The present invention relates to a preventive or therapeutic agent for disuse muscle atrophy.

  Muscle atrophy is broadly divided into disuse muscle atrophy and progressive muscle atrophy. Of these, disuse muscle atrophy is a significant change in skeletal muscle caused by long-term inactivity, Quantitative changes such as decrease and qualitative changes such as type transition at the muscle fiber and muscle protein level, such as cast fixation by long-term resting bed or fractures, exposure to microgravity (life in space), It is caused by the aging process.

  Conventionally, disuse muscle atrophy has been treated with sufficient exercise and rehabilitation, but these alone have a limited therapeutic effect. In addition, the treatment with drugs has a problem of complicated administration methods and side effects by doctors. For this reason, the treatment using vitamin E and polyphenol which exist also in nature is disclosed (patent document 1).

  On the other hand, proteins rich in branched chain amino acids (BCAA) are known to have excellent muscle-enhancing effects, and one of them, casein and the like, has been conventionally administered to those who require muscle enhancement.

JP 2001-89387 A

  However, casein and the like have a problem that the effect of preventing and treating disuse muscle atrophy is insufficient, and in particular, the recovery rate from disuse muscle atrophy is slow.

  The present invention has been made in view of the above circumstances, and an object thereof is to provide a preventive or therapeutic agent for disuse muscle atrophy containing an amino acid and excellent in effect.

  The present inventors have found that animal proteins rich in arginine, alanine, aspartic acid, and glycine are excellent in preventing or treating disuse muscle atrophy, and have completed the present invention. Specifically, the present invention provides the following.

  (1) Prevention of disuse muscle atrophy containing animal protein or a degradation product thereof and containing 1 mg of total nitrogen in amounts of arginine 250 mg or more, alanine 260 mg or more, aspartic acid 470 mg or more, and glycine 130 mg or more Or a therapeutic agent.

  (2) The preventive or therapeutic agent according to (1), wherein the animal protein includes fish meat protein.

  (3) The preventive or therapeutic agent according to (2), wherein the fish protein includes fish protein of fish belonging to the order of Codidae.

  (4) A prophylactic or therapeutic agent for disuse muscle atrophy containing fish protein or its degradation products of fish belonging to the order of Codidae.

  (5) The prophylactic or therapeutic agent according to any one of (1) to (4), wherein the disuse muscle atrophy is a symptom at least in a slow muscle.

  (6) The preventive or therapeutic agent according to any one of (1) to (5), wherein the protein or a degradation product thereof has a crude fat amount of 0.5% by mass or less.

  ADVANTAGE OF THE INVENTION According to this invention, the preventive or therapeutic effect of disuse muscle atrophy can be improved by using the animal protein or its degradation product rich in arginine, alanine, aspartic acid, and glycine.

It is a graph which shows an ingestion energy transition when the feed containing the prevention or treatment agent of disuse muscular atrophy which concerns on the Example of this invention is administered. It is a graph about the degree of muscle recovery when a preventive or therapeutic agent for disuse muscle atrophy according to an example of the present invention is administered. It is a graph about the degree of muscle recovery when a preventive or therapeutic agent for disuse muscle atrophy according to an example of the present invention is administered. It is a graph about the degree of muscle recovery when a preventive or therapeutic agent for disuse muscle atrophy according to an example of the present invention is administered. It is a graph about the degree of muscle recovery when a preventive or therapeutic agent for disuse muscle atrophy according to an example of the present invention is administered. It is a graph about the degree of muscle recovery when a preventive or therapeutic agent for disuse muscle atrophy according to an example of the present invention is administered. It is a graph about the degree of muscle recovery when a preventive or therapeutic agent for disuse muscle atrophy according to an example of the present invention is administered.

  Hereinafter, although an embodiment of the present invention is described, the present invention is not limited to this.

  The preventive or therapeutic agent for disuse muscle atrophy according to the first embodiment of the present invention contains animal protein or a degradation product thereof, and arginine is 250 mg or more, alanine is 260 mg or more, and aspartic acid is 470 mg with respect to 1 g of total nitrogen. As described above, glycine is contained in an amount of 130 mg or more. Since the amounts of arginine, alanine, aspartic acid and glycine are large, and other amino acids are contained in the animal protein in a well-balanced manner, disuse muscle atrophy is effectively prevented or treated.

  The present inventors have found that cod protein having a large amount of arginine, alanine, aspartic acid, and glycine is superior in preventing or treating disuse muscle atrophy than casein having a large amount of BCAA. In the prevention or treatment of atrophy, it was found that arginine, alanine, aspartic acid, and glycine are more important than BCAA (valine, leucine, isoleucine), which has been focused on the muscle strengthening effect.

  If the amounts of the above four amino acids are too small, it is difficult to sufficiently prevent or treat disuse muscle atrophy. On the other hand, if the amount is too large, the balance of other amino acids deteriorates, resulting in disuse. There is a tendency that preventive or therapeutic effects of muscular atrophy are not sufficiently obtained. Specifically, the lower limit of the amount of arginine is preferably 350 or more, and the upper limit is preferably 470 or less, more preferably 400 or less. The lower limit of the amount of alanine is preferably 260 or more, more preferably 350 or more, and the upper limit is preferably less than 380 (particularly 375 or less), more preferably 375 or less. The lower limit of the amount of aspartic acid is preferably 590 or more, more preferably more than 630 (especially 635 or more), and the upper limit is preferably 710 or less (especially 670 or less, 650 or less). The lower limit of the amount of glycine is preferably 130 or more, more preferably 260 or more, 280 or more, more than 310 (particularly 315 or more), and the upper limit is 400 or less (particularly 350 or less). The lower limit of the total amount of the four amino acids is preferably 1100 or more, more preferably 1540 or more and more than 1700 (particularly 1710 or more).

  The amino acid amounts in this specification all indicate the amino acid amount (mg / g nitrogen) relative to 1 g of total nitrogen, the nitrogen amount is measured based on the Kjeldahl method, and the amino acid amount is determined by the automatic amino acid analysis method (however, tryptophan is a high-speed liquid). (Specifically, as described in the report of the Japan Food Standard Composition Table, Amino Acid Composition Table 2010) reported by the Resource Survey Subcommittee).

  Since animal protein originally constitutes a part of an animal individual, it contains amino acids (essential amino acids, BCAA, etc.) involved in the tissue construction of the intake person in a well-balanced manner. However, since the disease targeted by the present invention is disuse muscle atrophy and is different from muscle recovery during normal or excessive exercise, a large amount of BCAA is not necessary. For this reason, the total content of BCAA may be 1000 or more, specifically 1070 or more and 1100 or more, while the upper limit is 1400 or less in terms of balance with other amino acids. Preferably, it is 1150 or less, 1140 or less, less than 1110 (especially 1105 or less).

  The prophylactic or therapeutic agent according to the present embodiment is composed of animal protein containing 1 mg of total nitrogen, 250 mg or more of arginine, 260 mg or more of alanine, 470 mg or more of aspartic acid, and 130 mg or more of glycine or a degradation product thereof. Alternatively, one or more of arginine, alanine, aspartic acid, and glycine may be added to animal protein or a degradation product thereof and adjusted to the above amount. The former is preferable in that the addition step of the amino acid can be omitted, and the latter is preferable in that the degree of freedom of animal protein used as a raw material or a degradation product thereof is wide.

  Therefore, the animal protein in this embodiment is not particularly limited, and milk protein such as casein, meat and animal meat such as cow, pig, sheep, rabbit, kangaroo, chicken such as chicken, turkey, quail, fish, white fish, etc. Or a processed product thereof (typically defatted). Fish meat protein, particularly white fish fish protein, particularly fish protein belonging to the order of codfish, is preferable in that it has a high content of arginine, alanine, aspartic acid, glycine and a low fat content. Table 1 shows the main amino acid composition of main animal protein and soy protein.

  Examples of the fish belonging to the order of the codfish include walleye pollock, minamidara, northern blue whiting, king clip, hake, madara and hoki. Among them, walleye pollock is preferable. For example, walleye pollack fish and Hoki fish meat processed in the following steps can be used as fish meat protein.

  Fish meat protein may be manufactured in the following steps, for example. The fish meat is cut into an appropriate size, the cut sample is frozen, and then freeze-dried with 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. Subsequently, fish protein can be obtained by removing ethanol. In addition, a protein having a crude fat amount of 0.5% by mass or less or a decomposed product thereof is preferable in that the energy intake can be reduced, and lipids may be removed by degreasing to obtain this. The amount of crude fat is measured by a conventionally known diethyl ether extraction method using a Soxhlet extractor.

  Decomposed products that have been decomposed so that fish protein is easily absorbed can also be used. Eventually, the effect of preventing or treating disuse muscle atrophy centered on the group of amino acids absorbed in the body is exerted. Therefore, even if the fish protein is partially or completely decomposed into amino acids, the above effect is achieved. Does not have a significant effect. Degradants can be obtained using proteolytic enzymes such as papain, trypsin, pepsin, bromelain, ficin and alcalase protease.

  The preventive or therapeutic agent for disuse muscular atrophy according to the second embodiment of the present invention contains fish protein of fish belonging to the order of Codella or a degradation product thereof. As mentioned above, the fish protein of fish belonging to the cod (especially walleye pollack) is rich in arginine, alanine, aspartic acid, glycine and contains other amino acids in a well-balanced manner. Excellent preventive or therapeutic effect on muscular atrophy can be obtained. Other elements are the same as those in the first embodiment, and thus the description thereof is omitted.

  Disuse muscle atrophy is a significant change in skeletal muscle caused by long-term inactivity, a quantitative change such as a decrease in muscle fiber diameter and a qualitative change such as type transition at the muscle fiber and muscle protein level, For example, it is caused by cast fixation by long-term resting bed or broken bone, exposure to microgravity (life in space), aging process, etc. In short, disuse muscle atrophy is a phenomenon in which muscle mass and strength decrease when muscles are not used for a long time, muscle tissue synthesis is suppressed, and decomposition is promoted. It is completely different in the subject and the mechanism of action from the increase in muscle mass during or overexercise, recovery from muscle damage (caused by necrosis or partial degeneration of skeletal muscle cells, blockage of communication with the governing nerve).

  Disuse muscle atrophy is a condition that occurs in one or both of the slow and fast muscles. Regarding the cod fish meat protein that can be used as an active ingredient in the present invention, WO2012 / 026575 pamphlet discloses a fast muscle-specific muscle-enhancing agent that changes a slow muscle to a fast muscle type. On the other hand, the preventive or therapeutic agent of the present invention can prevent or treat disuse muscle atrophy in any of the slow muscle and the fast muscle (that is, at least symptoms in the slow muscle).

  The preventive or therapeutic agent according to the present invention may further contain other nutritional components (such as carbohydrates), salt (such as NaOH), and pH adjusters (such as edible acids). The preventive or therapeutic agent according to the present invention further includes one or more of a pharmaceutically or physiologically acceptable base, carrier, excipient, binder, disintegrant, lubricant, and coloring agent. May include.

  Examples of the carrier and excipient 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, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, and carboxymethyl cellulose. Examples of the disintegrant include starch, agar, gelatin powder, crystalline cellulose, calcium carbonate, sodium bicarbonate, sodium alginate, sodium carboxymethylcellulose, and carboxymethylcellulose calcium. Examples of the lubricant include magnesium stearate, hydrogenated vegetable oil, talc and macrogol. The colorant may be any colorant that is allowed to be added to a pharmaceutical product.

  The preventive or therapeutic agent according to the present invention includes sucrose, gelatin, purified shellac, gelatin, glycerin, sorbitol, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, cellulose phthalate acetate, hydroxypropylmethylcellulose phthalate as necessary. Further, one or more coatings such as methyl methacrylate and methacrylic acid polymer may be provided. In addition, the preventive or therapeutic agent according to the present invention may contain a pH adjuster, a buffer, a stabilizer, a solubilizer, and the like as necessary.

  The preventive or therapeutic agent according to the present invention is administered orally. The form includes tablets such as sugar-coated tablets, buccal tablets, coated tablets and chewable tablets, capsules including troches, pills, powders and soft capsules, granules, suspensions, emulsions, syrups including dry syrups, and liquids. It is done.

  The preventive or therapeutic agent of the present invention is not limited depending on conditions such as the degree of symptoms, the age, weight, and health of the patient, but animal protein or a degradation product thereof is 100 μg to 10 g / kg / day for adults. Orally, it may be administered at an appropriate interval, orally once a day or divided into 2 to 4 times or more so that the amount is 0.1 g to 1 g / kg / day. Moreover, the preventive or therapeutic agent of this invention may be administered with food-drinks.

  A frozen Alaskan walleye fillet (Unicy) was cut into a size of about 1 cm × 1 cm × 1 cm with a band saw (Akiyama Machinery Co., Ltd., 600ST). The cut samples were arranged in a layer on a freeze-drying tray, and freeze-dried for 4 days and nights after preliminary freezing at −30 ° C. for 4 hours in a freeze-dryer (TF20-85ATNNN, manufactured by Tokyo Rika Kikai Co., Ltd.). 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 walleye pollack fish protein. About 1.5 kg of walleye fish protein was obtained from 10 kg of frozen walleye fillet. The composition of this protein is shown in Table 2.

(test)
High-fat diet (High fat-Casein, New Zealand Daily Board) was given to 5-week-old male SD rats, bred and acclimatized for 6 days, and then casted on the right hind limb of all rats. Breeding for a week (forming disuse muscle atrophy). Thereafter, the cast was removed and divided into groups, and a high fat diet or a diet in which only the protein source of the high fat diet was replaced with casein protein was fed for 3 weeks (n = 14 for each group). FIG. 1 shows the result of obtaining the intake energy from the intake during this period. In order to confirm muscle atrophy, dissection was performed at the time of grouping (n = 5). Table 3 shows the composition of the high fat feed (“Casein”) and the feed (“APP”) in which the protein of the high fat feed is replaced with cod protein.

  After the breeding, various skeletal muscles were collected, and the recovery rate of skeletal muscle weight was compared with the left hind limb (indicated as “non-gypsum” in the figure) that was not fixed. The results are shown in FIGS. In each figure and table, “Casein” indicates the results of the group administered with the high fat diet, and “APP” indicates the results of the group administered with the diet in which casein is replaced with walleye fish protein in the high fat diet. Moreover, the numerical value of each figure shows an average value +/- standard error. In FIG. 1, * indicates that P in an unpaired t test is less than 0.5, and ** indicates that P in an unpaired t test is less than 0.01. In FIGS. 2-4, the difference in the letters on each bar indicates that they are significantly different in Turkey's multiple comparison test.

  As shown in FIG. 1, the “Casein” group had significantly more feed intake than the “APP” group. However, as shown in FIGS. 2 to 4, the muscle recovery amount was significantly higher in the “APP” group than in the “Casein” group in both the slow and fast muscles.

  As shown in FIG. 2 regarding the soleus, which is the slow muscle, in the “APP” group, not only the fixed limb of the cast but also the muscular recovery amount of the unfixed limb was high. This result cannot be predicted from the disclosure of the pamphlet of WO2012 / 026575, and indicates that prevention or treatment of disuse muscle atrophy is based on a mechanism of action different from the increase in muscle mass in normal times.

  Moreover, as shown in FIGS. 5 to 7, the “APP” group showed the result that the muscle recovery amount was larger than that of the “Casein” group, and the limbs fixed with the cast and the same level or higher The difference in limb muscle mass that was not done was reduced. As a result, it was found that the fish protein can increase the muscle mass at an early stage with good balance with the muscle mass of other sites when the disuse muscle atrophy occurs locally and strongly.

Claims (6)

  An agent for preventing or treating disuse muscle atrophy containing animal protein or a degradation product thereof and containing 1 mg of total nitrogen in an amount of 250 mg or more, alanine 260 mg or more, aspartic acid 470 mg or more, and glycine 130 mg or more. .   The preventive or therapeutic agent according to claim 1, wherein the animal protein includes fish meat protein.   The prophylactic or therapeutic agent according to claim 2, wherein the fish meat protein contains fish meat protein of fish belonging to the order of Cod.   A preventive or therapeutic agent for disuse muscular atrophy containing fish protein of fish belonging to the order of cod or a decomposition product thereof.   The preventive or therapeutic agent according to any one of claims 1 to 4, wherein the disuse muscle atrophy is a symptom at least in a slow muscle.   The preventive or therapeutic agent according to any one of claims 1 to 5, wherein the protein or a degradation product thereof has a crude fat amount of 0.5% by mass or less.

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