JPH09124473A - Enhancer for physical fitness - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject pharmaceutical preparation, containing arginine as an essential ingredient, glutamine, a nucleotide, etc., as active ingredients and useful especially for increasing the physical fitness and improving locomotion capacity of infants, the sick or postoperative patients. SOLUTION: This enhancer for physical fitness contains (A) arginine as an essential ingredient and further (B) one or more ingredients selected from the group consisting of glutamine, a nucleotide or a nucleoside as an active ingredient. The ingredient (A) is preferably contained in an amount of 3-95g based on 100g solid content. The glutamine is preferably contained in an amount of >=3g based on 100g solid content and the nucleotide or nucleoside is preferably contained in an amount of >=0.05g based on 100g solid content. Furthermore, the enhancer preferably contains >=3g ingredient (A), 3-95g glutamine as the ingredient (B) and 0.05-1g nucleotide or nucleoside based on 100g solid content.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a physical strength-enhancing agent characterized by containing arginine as an essential ingredient, and further containing one or more kinds of ingredients selected from the group consisting of glutamine, nucleotides or nucleosides as an active ingredient. . Specifically, it is characterized by containing 3 g or more of arginine and 3 to 95 g or more of glutamine per 100 g of solid, or containing 3 g or more of arginine, 3 g or more of glutamine and 0.05 to 1 g of nucleotide or nucleoside. The present invention relates to a physical strength enhancer. Furthermore, it relates to a nutritional composition containing these. The invention is particularly suitable for infants,
It is effective in enhancing physical strength and improving exercise capacity of sick people and post-operative patients.

[0002]

2. Description of the Related Art In recent years, in the fields of exercise physiology, nutritional physiology, etc., various athletes have been given dietary guidance for the purpose of improving physical strength such as endurance, muscular strength, and exercise ability. For example, proteins are necessary for strengthening muscle strength, and fats and carbohydrates are important energy sources. In addition, calcium is required for bone strengthening, and iron, which is a constituent of hemoglobin, plays an extremely important role in transporting oxygen in the body. For example, it has been reported that high-fat diet improves energy production ability and can promote establishment of efficient energy metabolism, especially the effectiveness of monounsaturated fatty acids (Yashiro, Monthly Food Chemical 1993.
-6, 38, 1993), or that high exercise capacity was obtained when a high protein diet was taken (Wishrart et al., J. Physiol., Vo.
l.82, p189 (1934)). However, these reports were aimed at athletes with high energy consumption, and could not be applied to sick people with impaired digestive absorption and metabolic functions, postoperative patients or infants with immature functions.

Physical strength is said to be classified into athletic ability typified by agility and muscular strength, and physical strength related to health such as muscular endurance and whole body endurance (Tomoko Shikuda, Pediatric practice, 1994, No. 11, 1994). , 1933). It is needless to say that proper nutrition and proper exercise are required to improve exercise capacity, but it is quite possible that the sick person, postoperative patient or infant cannot exercise. For those people,
Enteral nutrition using peptides and amino acids with good digestion and absorption, or high-calorie infusion that supplements nutrition by infusion is widely used as a nutrition method, but it is not intended to recover physical strength and exercise capacity. , There is no known physical strength enhancement method for infants. However, there has been a demand for the development of a physical strength enhancer for promptly recovering or acquiring physical strength or athletic ability for sick people and postoperative patients with markedly decreased physical strength, and even for infants.

Further, in recent years, it has become known that various components are involved in the regulation of immunocompetence and metabolic function, and they have come to be used in various nutritional supplements. For example, arginine is a component that is said to be a semi-essential amino acid for infants, is necessary to detoxify the toxic ammonia produced by the metabolism of proteins in the body, and also functions as a precursor of polyamines. To get involved,
It is known to have an effect of improving nitrogen utilization efficiency in the body, an immunostimulating effect and the like. Focusing on such a function, a patent has been filed for infant formula containing arginine (JP-A-61-192245), but the relationship between arginine and physical fitness has not been known.

Glutamine is an amino acid which accounts for 50 to 60% of the skeletal muscle amino acid pool and about 20% of the plasma amino acid pool, and is said to be a major energy source in small intestinal epithelial cells. Glutamine deficiency is also said to be the cause of intestinal atrophy, and its effects on the immune system have been suggested.
Therefore, in recent years, attention has been paid to the fields of enteral nutritional supplements and infusions, and techniques relating to the use thereof have been disclosed (Japanese Patent Laid-Open Nos. 2-119762, 3-264525, and 5-236909).
Furthermore, glutamine has received attention in the field of sports physiology, and it has been shown that it is effective in supplementing glycogen consumed by exercise and in recovering immune function during fatigue (Masao Yoshida, Monthly Food Chemical, 1994-10, 46). But,
It is not intended for sick people or infants who are unable to exercise sufficiently.

[0006] Nucleotides are basic units constituting nucleic acids and are essential components for all living organisms. Nucleotides have a structure in which phosphate is bound to six types of nucleosides, cytidine, uridine, adenosine, guanosine, thymidine, and inosine. Almost all cells and organs in the body have the activity of synthesizing nucleotides, and thus have not been recognized as nutritional components for a long time. However, in recent years it has become known that nucleotides taken orally control fatty acid metabolism in the body and are involved in the immune response, and the incorporation of nucleotides in enteral nutritional supplements and infant formula has been investigated. It's coming. However, the relationship between nucleotide intake and physical fitness has never been studied.

[0007]

In view of the above situation, the present inventors have focused their attention on various nutrients that have been attracting attention as special nutritional ingredients in recent years, and as a result of diligent research, the general public and the sick person,
We have found a physical strength enhancer that can recover or acquire physical strength of postoperative patients and infants without imposing a burden on their digestion, absorption and metabolic ability. That is, the above-mentioned physical strength enhancer was found by combining arginine as an essential component and further combining one or more components selected from the group consisting of glutamine, nucleotides or nucleosides. Therefore, an object of the present invention is to provide a physical strength enhancer characterized by comprising arginine as an essential component and further comprising one or more components selected from the group consisting of glutamine, nucleotides or nucleosides.

[0008]

The present invention is characterized by containing arginine as an essential ingredient and further containing one or more kinds of ingredients selected from the group consisting of glutamine, nucleotides or nucleosides as an active ingredient. Regarding agents. Furthermore, it relates to a nutritional composition containing the same.

The physical strength-enhancing agent of the present invention is a sick person,
Any form that can be easily taken by postoperative patients and infants may be used. For example, for oral administration, tablets, capsules, granules, powders,
Examples include drinks. At this time, if necessary, formulation components usually used in formulations such as excipients, binders, lubricants, emulsifiers and the like may be added. Further, the physical strength enhancer of the present invention may be blended not in the form of a single preparation but in nutritional compositions such as various pathological diets, oral / enteral nutritional supplements, modified milk, beverages or baby foods. Examples of the modified milk include infant formula, follow-up milk, proteolytic milk, and special nutritional formula. The composition of the nutritional composition contains proteins, lipids, sugars, vitamins and minerals as main components in addition to the physical strength enhancer component of the present invention. In this case as well, regardless of the form, any form such as solid, powder, liquid, gel, or slurry may be used as long as it is an easily ingested form. At this time, it is preferable to add 0.1 to 10% by weight of the physical strength enhancer per solid of the nutritional composition.

The arginine which is an active ingredient of the present invention is, in addition to L-arginine which is a free form, peptide-type arginine whose main amino acid is L-arginine, or a protein having a high arginine content such as isolated soybean protein. Further, it may be a peptide type arginine obtained by hydrolyzing a protein having a high arginine content. Also, a combination of these may be used. Glutamine may be peptide glutamine which forms a major amino acid in addition to free L-glutamine, or peptide glutamine obtained by hydrolyzing a protein containing a large amount of glutamine such as gluten. May be a combination of. The nucleotide or nucleoside may be in a free form or a sodium or potassium salt, respectively. There is almost no difference in activity between nucleotides and nucleosides, and either one may be used. In order to enhance physical strength, it is necessary to make arginine an essential component among the above components, and to administer at the same time one or more components selected from glutamine, nucleotides or nucleosides. The daily dose of the product of the present invention is preferably 1 to 10 g for adults and 0.1 to 2 g for infants. In addition, the product of the present invention may be orally administered once a day in a prescribed amount, or may be administered in several divided doses between meals, before meals and after meals.

There is no problem even if the physical strength enhancer of the present invention is added to nutritional compositions such as infant formula and enteral nutritional supplements. The protein constituting the nutritional composition containing the physical strength enhancer of the present invention is skim milk, casein, cheese whey, whey protein concentrate (WPC), whey protein isolate (WP).
Milk proteins such as I) and their fractions αS-casein, β-casein, α-lactalbumin and β-lactoglobulin, and egg proteins such as egg yolk protein, egg white protein and ovalbumin. Alternatively, soybean proteins such as defatted soybean protein, isolated soybean protein and concentrated soybean protein can be mentioned. Alternatively, proteins such as wheat gluten, fish meat protein, animal meat protein and collagen may be used. Further, it may be a peptide fraction or a free amino acid prepared by treating the above-mentioned protein fraction, acid or enzyme. The free amino acid can be used not only as a nitrogen source but also for imparting a specific physiological action, and examples thereof include taurine, cystine, cysteine and the like. The amount of protein, peptide, and free amino acid compounded is
5 to 30% by weight per solid content is suitable. As sugars, starch, soluble polysaccharides, dextrin, sucrose,
Lactose, maltose, monosaccharides such as glucose and fructose, and oligosaccharides such as galactooligosaccharide, fructooligosaccharide and lactulose can be mentioned.
Mix more than one kind. The sugar content is preferably 30 to 80% by weight based on the solid content of the nutritional composition.
In addition, an artificial sweetener such as aspartame may be used depending on the application, and the blending amount in this case is 0.
05 to 1.0% by weight is suitable. As the lipid, milk fat, lard, animal fats and oils such as beef tallow and fish oil, soybean oil, rapeseed oil, corn oil, coconut oil, palm oil, palm kernel oil, safflower oil, perilla oil, linseed oil, evening primrose oil, medium Vegetable oils and fats such as chain fatty acid triglyceride (MCT) and cottonseed oil,
Furthermore, any one or more of these fractionated oils, hydrogenated oils, and transesterified oils can be used. The lipid content is preferably 40% by weight or less per solid of the nutritional composition.

Regarding vitamins and minerals, refer to "CO of special purpose foods including infant foods, issued by Japan International Dairy Federation.
DEX Standards and Related Sanitary Work Regulations, CAC / VOL.IX- 1st Edition and Supplements 1,2,3,4 (1993) "," Published by Food and Science Co., 1993 Edition Specified Food Additives Handbook (Revised 31 Edition)
(1993) ”and“ Food and Scientific Publishing, Notification System Food Additives / Food Materials Natural Products Handbook (12th Edition) (1992) ”can be used for nutritional composition of vitamins and minerals. One or more of these can be used. Examples of vitamins include vitamins A, B, C,
D, E, K, folic acid, pantothenic acid, β-carotene, nicotinic acid amide, carnitine, choline, inositol, biotin and the like can be mentioned, and the compounding amount thereof is preferably 10 mg to 5 g per 100 g of the solid content of the nutritional composition. Examples of minerals include calcium, magnesium, potassium, sodium, iron, copper, zinc, phosphorus, chlorine, manganese, selenium and iodine, and the amount of these is preferably 1 mg to 5 g per 100 g of the nutritional composition.

[0013]

The present invention will be described in more detail with reference to the following examples, which should not be construed as limiting the invention thereto.

[0014]

[Example 1] Preparation of physical strength enhancer of the present invention (tablet) L-arginine 50 g, L-glutamine 50 g (both Kyowa Hakko Co., Ltd.), and 5'-cytidine monophosphate, 5'-uridine monophosphate, 5 ' 1 g of a nucleotide mixture prepared by mixing -adenosine monophosphate, 5'-guanosine monophosphate, 5'-inosin monophosphate (both Yamasa)
Were uniformly mixed, and tablets were obtained by the direct tableting method. At this time, the weight per tablet was 1 g.

[0015]

[Example 2] Preparation of physical strength enhancer of the present invention (powder) 200 g of wheat gluten (Nacalai Tesque) was dissolved in ethanol and suspended in 1% acetic acid while stirring. Morcine (Protease Type VIII, Sigma) was reacted with this suspension at 37 ° C. for 24 hours, and actinase (Kaken Pharmaceutical Co., Ltd.) was further reacted at 37 ° C. for 24 hours. The free amino acid produced by this reaction was removed by treatment with an ultrafiltration membrane having a molecular weight cutoff of 500 (Diaflow Membrane YC05, Amicon) to give a glutamine content of 4
142 g of 0% by weight of glutamine peptide was obtained. 50 g of L-arginine (Kyowa Hakko Co., Ltd.) and 1 g of the nucleotide mixture prepared in the same manner as in Example 1 were uniformly mixed with the mixture to prepare a powder having a particle size of 350 μm or less.

[0016]

[Example 3] Preparation of physical strength enhancer of the present invention (prepared milk powder) 5.04 kg of skim milk was added to whey protein concentrate (WPC,
158 g of Japan Proten Co., Ltd.) and 924 g of lactose were added. In addition to this, water-soluble vitamins (vitamins B ₁ , B ₂ , B
₆ , B ₁₂ , C, niacin, folic acid, pantothenic acid, biotin, choline, inositol) and minerals (calcium carbonate, potassium chloride, magnesium sulfate, ferrous sodium citrate, copper sulfate, zinc sulfate) respectively.
Prepared fat 5 in which 5 g was added and dissolved, and further fat-soluble vitamins (vitamins A, D, E, K, β-carotene) were dissolved
78g was added and mixed. It is homogenized, sterilized according to the usual method, then concentrated and dried to formulate milk powder 2.1 kg.
I got To this, 50 g of L-arginine, 50 g of L-glutamine (both Kyowa Hakko Co., Ltd.), and 21 g of a mixture of 1 g of the nucleotide mixture prepared in the same manner as in Example 1 were uniformly mixed, and 2.1 kg of a formula powder containing a physical strength-enhancing component was prepared. Obtained.

[0017]

Example 4 Preparation of Physical Strength Enhancer of the Present Invention (Powdered Milk Powder) Whey Protein Concentrate (WPC, Nippon Proten) 88
0 g and lactose (5.2 kg) were dissolved in 20 kg of warm water, and a solution of milk (7.5 kg) and casein (490 g) dissolved in a predetermined alkali was added. Water soluble vitamins (vitamins B _{1, B 2} , B ₆ , B ₁₂ , C, niacin,
Folic acid, pantothenic acid, biotin, choline, inositol) and minerals (calcium carbonate, potassium chloride,
Prepared fat 2 in which 7.5 g of magnesium sulfate, sodium ferrous citrate, copper sulfate and zinc sulfate were added and dissolved, and further fat-soluble vitamins (vitamins A, D, E, K, β-carotene) were dissolved 0.5 kg was added and mixed. This was homogenized, sterilized by a conventional method, concentrated and dried to obtain 10 kg of infant formula. to this,
100 g of a 1: 1 mixture of L-arginine and the glutamine peptide prepared in Example 2 was uniformly mixed to obtain 10.0 kg of a formula powder containing a strength-enhancing component.

[0018]

[Example 5] Preparation of the physical strength enhancer of the present invention (milk powder for childcare-2) Yeast RNA (Wako Pure Chemical Industries, Ltd.) 100 g was dissolved in warm water, and nuclease P1 (Penicillium citrinum origin, Wako Pure Chemical Industries, Ltd.) was added thereto. After adding and reacting at 37 ° C. for 24 hours,
Furthermore, adenyl deaminase (Aspergillus sp., Sigma) was reacted at 37 ° C. for 6 hours. An ultrafiltration membrane with a molecular weight cutoff of 500 (diaflow membrane YC0
5, unreacted RNA was removed by Amicon) to obtain 72 g of nucleotide. Soy peptide (arginine content 7.7%, Fuji Oil Co., Ltd.) 50 g
0 g and the glutamine peptide 490 prepared in Example 2
g to obtain a physical strength enhancer (1 kg). Separately, 8.4 kg of whey protein concentrate (WPC, Nippon Proten Co., Ltd.) and 47 kg of lactose were dissolved in 300 kg of warm water, and a solution of 7.1 kg of casein in a predetermined amount of alkali was added. Water soluble vitamins (vitamins B ₁ , B ₂ , B ₆ , B ₁₂ , C, niacin, folic acid,
1 kg of pantothenic acid, biotin, choline, inositol) and minerals (calcium carbonate, potassium chloride, magnesium sulfate, sodium ferrous citrate, copper sulfate, zinc sulfate) were added and dissolved, and fat-soluble vitamins (vitamin A) , D, E, K, β-carotene) was dissolved in 27.4 kg of the prepared fat, and 1 kg of the physical strength enhancer prepared above was added and mixed. This is homogenized, sterilized according to the usual method, then concentrated and dried to prepare infant formula 1
00 kg was obtained.

[0019]

[Example 6] Physical strength enhancement test 1 As a test feed, casein 25%, corn starch 5
3.5%, cellulose powder 8.0%, sucrose 3.0
%, Soybean oil 6.0%, AIN-76 composition (J. Nutr., Vo
l.107, p1340 (1977)) Mineral mixture 3.5
%, A mixture of vitamins 1.0% was prepared.
Separately from this, a physical strength enhancer was prepared using L-arginine, L-glutamine, and nucleotides. Table 1 shows each composition of the physical strength enhancer. Dextrin was added to these as an excipient to prepare 100 g of each. As a control, a preparation containing only an excipient was also prepared. still,
This was dissolved in water and used at each administration.

[0020]

Table 1 Test agent 1: Arginine 1 g Test agent 2: Arginine 3 g Test agent 3: Arginine 95 g Test agent 4: Glutamine 95 g Test agent 5: Nucleotides 1.0 g Test agent 6: Arginine 3 g + glutamine 95 g Test agent 7: Arginine 3 g + Nucleotides 1.0 g Test Agent 8: Arginine 3 g + Glutamine 3 g + Nucleotides 0.05 g

As experimental animals, 3-week-old male SD rats (body weight: 35 to 45 g) were preliminarily reared for 5 days with 5 animals in each group, and then fed ad libitum for 28 days.
During this period, the above-mentioned physical strength enhancer was forcibly orally administered daily at a rate of 1 g per 1 kg of body weight. The exercise test was carried out by a swimming test according to the method of Tanaka et al. (Study on Physical Education, 33 (2), 155, 1988). From the 21st day after the start of the test, daily swimming exercises were carried out for 10 minutes, the rats were acclimated to water, and the all-out test was carried out on the 28th day of the test. this is,
A weight corresponding to 4% of the body weight was applied to the tail of the rat to perform swimming, and the time when it sank below the surface for 10 seconds was taken as all-out, and the time from the start of swimming to all-out was measured.
This is a method of determining athletic ability. The results are shown in FIG.

[0022]

FIG.

From these results, it was shown that arginine alone was effective in enhancing the physical strength, but it was shown to be more effective when arginine and glutamine, arginine and nucleotide, or arginine, glutamine and nucleotide were administered. However, even if glutamine and nucleotide were administered alone, the physical strength enhancing effect was not observed.

[0024]

Example 7 Physical Strength Enhancement Test 2 A physical strength enhancer having the composition shown in Table 2 was supplemented with sucrose as a bulking agent to give 100 g, which was added to the test feed of Example 1 as 1
The mixture was mixed at a weight percentage, and each of them was used as test meals 1 to 8. In addition, as a target, a feed containing 1% by weight of sucrose used as a bulking agent in preparing a test agent was used as a basic feed.
Two-week-old SD male rats (body weight 22-
32g) was used. On the 17th day after birth, the animals were weaned early, apart from their mothers, allowed to freely ingest each test meal and water, and bred for 4 weeks. On the 28th day from the start of the test, the soleus muscle of the hind limb and the extensor carpi radialis longus of the forelimb were collected under ether anesthesia, and blood was collected from the posterior vena cava. The muscle weight was measured and the hemoglobin concentration in blood was measured by Hemoglobin Test Wako (Wako Pure Chemical Industries, Ltd.). The ratio of the weight of the soleus muscle and the extensor carpi radialis to the body weight is shown in FIGS. 2 and 3, and the hemoglobin concentration in blood is shown in FIG.

[0025]

[Table 2] Test agent 1: Arginine 1 g Test agent 2: Arginine 3 g Test agent 3: Arginine 3 g + glutamine 3 g Test agent 4: Arginine 3 g + glutamine 95 g Test agent 5: Arginine 3 g + nucleoside 0.05 g Test agent 6: Arginine 3 g + nucleoside 1 g Test Agent 7: Arginine 1 g + Glutamine 95 g + Nucleoside 1 g Test Agent 8: Arginine 3 g + Glutamine 3 g + Nucleoside 0.05 g

[0026]

FIG. 2

[0027]

FIG. 3

[0028]

FIG. 4

From these results, it was shown that each test meal except test meal 1 and test meal 7 showed an increase in muscle mass without any particular training. It was also shown that the hemoglobin level in blood was higher in these groups than in the control diet group. That is, by orally and continuously ingesting arginine, glutamine, nucleotides or nucleosides, protein metabolism is improved, muscle mass is increased, and further iron absorption from the digestive tract is improved, so that hemoglobin in blood is increased. It was suggested that the physical strength increased and the endurance of the whole body improved.

[0030]

From the above results, according to the present invention, arginine is contained as an essential ingredient, and further, one or more kinds of ingredients selected from the group consisting of glutamine, nucleotides or nucleosides are contained as an active ingredient. An agent is provided. Furthermore, a physical strength-enhancing nutritional composition containing the same is provided. The physical strength enhancer of the present invention is particularly effective for increasing physical strength and improving exercise capacity of infants, sick people, and postoperative patients.

[Brief description of the drawings]

FIG. 1 shows the effect of the physical strength enhancer of the present invention on swimming time in rats.

FIG. 2 shows the effect of the nutritional composition containing the physical strength enhancer of the present invention on the soleus muscle of the hind limb of rats.

FIG. 3 shows the effect of the nutritional composition containing the physical strength enhancer of the present invention on the extensor carpi radialis longus of the forelimb in rats.

FIG. 4 shows the effect of a nutritional composition containing the physical strength enhancer of the present invention on blood hemoglobin concentration in rats.

Claims (6)

[Claims] 1. A physical strength enhancer, which comprises arginine as an essential component, and further contains, as an active ingredient, one or more components selected from the group consisting of glutamine, nucleotides and nucleosides. 2. Arginine of 3 to 9 per 100 g of solid.
The physical strength enhancer according to claim 1, which contains 5 g. 3. The physical strength enhancer according to claim 2, which contains 3 g or more of glutamine per 100 g of solid. 4. The physical strength enhancer according to claim 3, which contains 0.05 g or more of nucleotides or nucleosides per 100 g of solid. 5. The physical strength enhancer according to claim 1, which contains 3 g or more of arginine, 3 to 95 g of glutamine, and 0.05 g to 1 g of nucleotide or nucleoside per 100 g of solid. 6. A nutritional composition containing the physical strength enhancer according to claim 1.