JP2005289861A - Composition for promoting storage of glycogen - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition used for promoting the storage of glycogen. <P>SOLUTION: This composition used for promoting the storage of the glycogen is obtained by containing milk whey protein as an active ingredient. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

Background of the Invention

TECHNICAL FIELD The present invention relates to a composition used for promoting storage of glycogen and its use as a food and medicine.

Background Art Glycogen is the main storage form of carbohydrates present in animals, and is mainly contained in the liver and muscles. Although the amount stored in the muscle rarely exceeds 1%, the muscle stores approximately 3-4 times the glycogen of the liver because the total amount of muscle tissue in the animal is greater than the liver. Stored glycogen in the liver is converted into glucose by being decomposed and carried into tissues, and is used to maintain blood sugar such as between meals. Stored glycogen in muscle is converted to glucose by decomposition and used directly as an energy source during exercise.

  There are two pathways for carbohydrate metabolism to maintain blood glucose homeostasis. One is a pathway (glycolysis system) that uses glucose as energy, and the other is a pathway (gluconeogenesis) that regenerates deficient glucose from fatty acids, glycogenic amino acids, and the like. The glycolytic system metabolizes glucose and, when oxygen is present, utilizes oxygen through the mitochondrial respiratory chain to produce a large amount of energy in the living body. On the other hand, when a sufficient amount of carbohydrates cannot be obtained from food, glucose is renewed through the gluconeogenic pathway to meet the body's glucose demand. Thus, in order to maintain life, it is important to keep supplying glucose constantly.

  The main pathways of glycolysis and gluconeogenesis are as shown in FIG. In the glycolytic system, glucose is metabolized to pyruvic acid through a 9-step reaction. On the other hand, in gluconeogenesis, the reverse route is followed to metabolize pyruvic acid to glucose. Of the nine steps that metabolize glucose to pyruvate, the six steps are catalyzed by a reversible reaction of a common enzyme. For example, in glycolysis, fructose 6-phosphate is produced from glucose 6-phosphate by a catalytic reaction with phosphohexose isomerase. Also in the gluconeogenic system, glucose 6-phosphate is produced from fructose 6-phosphate by the catalytic reaction of phosphohexose isomerase, which is the same enzyme as the glycolytic system.

  However, there are places where gluconeogenesis does not simply reverse the glycolysis. It is in three places, between glucose and glucose 6-phosphate, between fructose 6-phosphate and fructose 1,6-bisphosphate, and between phosphoenolpyruvate and pyruvate. Specifically, in glycolysis, glucose produces glucose 6-phosphate by the catalytic reaction of glucokinase (or hexokinase in muscle), whereas in gluconeogenesis, glucose 6-phosphate is glucose 6-phosphatase. Glucose is produced by a catalytic reaction. In the glycolysis system, fructose 6-phosphate produces fructose 1,6-bisphosphate by the catalytic reaction of phosphofructokinase, whereas in gluconeogenesis, the reverse reaction is caused by fructose 1,6-bisphosphatase. Metabolized by catalytic reaction. Furthermore, in glycolysis, phosphoenolpyruvate generates pyruvate by the catalytic reaction of pyruvate kinase, whereas in gluconeogenesis, the reverse reaction occurs through multiple steps to produce oxaloacetate, via oxaloacetate. It is metabolized to phosphoenolpyruvate by the catalytic reaction of phosphoenolpyruvate carboxykinase. The catalytic reaction by these enzymes is a physiologically irreversible reaction because a large amount of energy is released as heat. Therefore, regulating the enzymes involved in these irreversible reactions can be a very important key to control sugar metabolism, ie glycogen metabolism.

  In sports, physical strength, especially endurance, anti-fatigue, fatigue recovery, etc. are important. Muscle fatigue due to exercise occurs when glycogen in the tissue that is the source of energy production is consumed and reaches a certain limit. In other words, when glycogen in the tissue is depleted, it becomes unable to exercise. In addition, a positive correlation has been reported between glycogen storage amount and endurance in tissues (Acta Phsiol. Scand., 71, 140-150, 1967). For these reasons, it is important to increase the amount of glycogen stored in the tissue in order to increase endurance, anti-fatigue, fatigue recovery, and the like. Therefore, it is desired to develop substances and methods that increase the amount of tissue glycogen stored more effectively.

  In order to maintain stamina and reduce fatigue, ingesting glucose or other energy sources during exercise saves glycogen consumption in the muscles, delays the decrease in blood sugar levels, and supplies glycogen. It is valid. For example, in J. Apply. Physiol., 72, 1854-1859, 1992 (Non-patent Document 1), supplementation such as a combination of a carbohydrate and a protein is advantageous for quickly restoring tissue glycogen after exercise. And

  In addition, J. Nutr. Sci. Vitaminol., 29, 45-54, 1983 (Non-Patent Document 2) states that citric acid can be used as a food material that increases the amount of glycogen stored in tissues. ing. Ingestion of citric acid can increase the amount of glycogen stored in the liver. The mechanism of action is to activate glucokinase, a glycolytic enzyme in the liver, inhibit phosphofructokinase, activate fructose 1,6-bisphosphatase, a gluconeogenic enzyme, and glucose 6- It inhibits phosphatase. Thus, it has been clarified that glycogen storage by ingesting citric acid largely involves the control of glycolysis and key enzymes of gluconeogenesis.

  In addition, WO 01/021182 (Patent Document 1) discloses a physical fitness enhancer and a glycogen accumulation promoter comprising a polylactic acid mixture. It is said that glycogen accumulation in tissues is promoted by ingesting a mixture of cyclic and chain polylactic acid having a condensation degree of 3 to 20.

International Publication No. 01/021182 Pamphlet J. Apply. Physiol., 72, 1854-1859, 1992 J. Nutr. Sci. Vitaminol., 29, 45-54, 1983

Summary of the Invention

  The present inventors have now found that milk whey protein has the action of controlling the glycolytic system and key enzymes of gluconeogenesis. Further, the present inventors have found that milk whey protein has an effect of significantly promoting glycogen storage in tissues. The present invention is based on these findings.

  Accordingly, an object of the present invention is to provide a composition used for promoting storage of glycogen, and a food and a pharmaceutical composition comprising the composition.

  The composition used for promoting storage of glycogen according to the present invention comprises milk whey protein as an active ingredient.

  Moreover, the composition used for the control of the glycolytic enzyme and / or gluconeogenic enzyme according to the present invention comprises milk whey protein as an active ingredient.

  The food used for promoting storage of glycogen according to the present invention contains milk whey protein as an active ingredient.

  The pharmaceutical composition used for promoting storage of glycogen according to the present invention comprises milk whey protein as an active ingredient.

  Since the composition according to the present invention contains milk whey protein as an active ingredient, it has no side effects and is excellent in safety, and can be advantageously used for promoting storage of glycogen. Furthermore, according to the present invention, by efficiently and quickly increasing glycogen storage in tissues, particularly liver and muscle, it is possible to prevent physical strength increase or decrease, increase exercise capacity, improve endurance, recover from fatigue or sugar. It is possible to advantageously improve quality metabolism. Furthermore, according to the present invention, by promoting glycogen storage, it is possible to maintain a higher glycogen storage amount under conditions that consume glycogen than in the case where milk whey protein is not used. For example, a high glycogen storage amount can be maintained even after exercise.

DETAILED DESCRIPTION OF THE INVENTION

Milk whey protein whey (whey) refers to a water-soluble component remaining after removing fat, casein protein, and fat-soluble vitamins from milk. The main components of whey include milk whey protein, lactose, minerals, and water-soluble vitamins (B1, B2, nicotinic acid, C, etc.). As used herein, “milk whey protein” means “milk whey protein” found in the whey. The main components of milk whey protein include, for example, β-lactoglobulin (about 45 to 55% in milk whey protein), α-lactalbumin (about 15 to 25% in milk whey protein), serum albumin, Examples thereof include immunoglobulins and lactoferrin. And according to one aspect | mode of this invention, the composition of the essential amino acid in milk whey protein is made into the ratio shown in Table 1, for example.
Table 1. Essential amino acid composition
Constituent amino acid ratio (%)
Histidine 1.9 to 2.3
Isoleucine 4.6-5.6
Leucine 10.8 to 13.2
Lysine 8.3 to 10.1
Methionine 2.2-2.8
Phenylalanine 3.1-3.9
Threonine 4.4-5.4
Tryptophan 1.7-2.1
Valine 5.1-6.3
The origin of the milk whey protein used in the present invention is not particularly limited, but is usually mammalian milk, more preferably cow milk.

  As the milk whey protein used in the present invention, cheese whey or casein whey obtained by the cheese or casein production process can be used. In the present invention, a whey concentrate obtained by concentrating whey into a solid form may be used directly, but preferably, a fraction containing a high concentration of milk whey protein is obtained and used. . For example, a fraction obtained by spray-drying whey after ultrafiltration or by washing and drying a precipitate formed by heating at 90 ° C. or higher under weak acidity can be used in the present invention. .

  Examples of whey concentrates that can be used in the present invention include, for example, whey powder obtained by concentrating and drying whey, and milk whey protein concentrate (Whey Protein) obtained by concentrating whey by ultrafiltration (UF) and then drying. Concentration (WPC), after removing fat in whey, UF concentrated defatted WPC (low fat and high protein), milk whey protein isolate (WPI) that selectively isolates only protein from whey, Examples include nanofiltration concentrated desalted whey. In the whey concentrate used in the present invention, the milk whey protein is preferably 20 to 100% by weight, and more preferably 50 to 100% by weight.

  In addition, a hydrolyzate of milk whey protein obtained by enzyme, acid, or alkali treatment can be used in the present invention as long as it has an action of promoting storage of glycogen of the present invention. Enzyme, acid, or alkali treatment conditions (for example, substrate concentration, enzyme amount, treatment temperature, pH, time, etc.) can be easily determined by those skilled in the art through experiments to determine optimum or suitable conditions. And within normal creative ability. As an enzyme used for hydrolysis of milk whey protein, it is harmless in food hygiene, for example, a protease derived from a microorganism belonging to the genus Bacillus or Aspergillus, a papain derived from papaya, a promeline derived from pineapple, etc. Protease, animal-derived pancreatin, trypsin and the like, and these can be tried singly or in combination.

Composition and Use as Food and Pharmaceutical Composition The present invention provides a composition, food and pharmaceutical composition comprising milk whey protein as an active ingredient. Here, “comprising as an active ingredient” means that it may contain a carrier according to a desired purpose and application, and naturally includes a case where it contains other components that can be used in combination.

  Moreover, according to another aspect of the present invention, there is provided use of milk whey protein for producing a composition for promoting storage of glycogen. According to another aspect of the present invention, there is provided use of milk whey protein for producing a food for promoting storage of glycogen. According to another aspect of the present invention, there is provided use of milk whey protein for producing a pharmaceutical composition for promoting storage of glycogen.

  The content of the active ingredient in the present invention can be arbitrarily set depending on its use, but is preferably 15 to 95% by weight, more preferably 20% with respect to the total amount of the composition, food or pharmaceutical composition. It is made into -95weight%, Especially preferably, it is made into 50-95weight%.

  The daily intake of the composition, food or pharmaceutical composition according to the present invention depends on the recipient, the age and weight of the recipient, symptoms, administration time, dosage form, administration method, combination with other ingredients, etc. Although it can be determined, the amount of milk whey protein per adult is 20 to 120 g, preferably about 40 g. If it is this range, it is sufficient quantity to exhibit the glycogen storage promotion effect, and if it is more than this, there may be a case where the kidneys and liver may be burdened. According to a survey by the United States Department of Agriculture (USDA), the protein content in 200 ml of normal milk is about 7.86 g, and milk whey protein accounts for about 20% of the total milk protein, so the intake is 40 g. Corresponds to about 5.1 L of milk. This amount is not a safety problem, but is not an amount that can be consumed in a normal diet. Therefore, in this invention, it is preferable to administer milk whey protein used as the said intake using the milk whey protein obtained by concentrating by a fixed process.

  The composition, food or pharmaceutical composition according to the present invention can be in any form such as a solid, powder, liquid, liquid paste, etc., as long as the desired effect is achieved. Oral preparations such as granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions and suspensions can be used.

  The composition, food, or pharmaceutical composition according to the present invention can be produced by a method commonly used in the art. Milk whey protein can be added during the production process of the product or in the final product. If there is a step of modifying the milk whey protein during the production process, the milk whey protein may be added after the step. Good.

  In addition, since the active ingredient of the composition, food or pharmaceutical composition according to the present invention is milk whey protein, mammals (eg, humans, mice, rats, rabbits, dogs, cats, cows, horses, pigs, Safe for monkeys, etc.).

  When the composition according to the present invention is used as it is or in the form of food, the composition or food is used to prevent physical strength from increasing or decreasing, to increase exercise capacity, to improve endurance, to recover from fatigue or to improve carbohydrate metabolism. Can be used for purposes. Therefore, according to another aspect of the present invention, the composition or food according to the present invention is used for prevention of physical strength increase or decrease, enhancement of exercise capacity, improvement of endurance, recovery from fatigue or improvement of carbohydrate metabolism. It is done.

  The composition or food according to the present invention can be used for sports such as marathons, which continuously exercise for 10 minutes or longer, sports that require repeated dash and walking, such as soccer and rugby, short-distance swimming, and land. However, it can be used advantageously in competitions where the duration of one exercise is short but the competition is repeated many times during the same day. Furthermore, the composition and food according to the present invention can be said to be suitable for consumers who want to keep exercising without feeling fatigue, suppress a decrease in athletic ability, or prevent accidents due to a decrease in concentration.

  Here, in the present invention, “food” is used in the meaning including health food, functional food, food for specified health use, and food for the sick. Furthermore, "food" can be used in the sense of including feed when used for mammals other than humans.

  The form of “food” is not particularly limited, and can be, for example, a beverage form. Thus, according to another aspect of the present invention, the food according to the present invention is provided in the form of a beverage.

  Furthermore, since the food according to the present invention has an action to promote storage of glycogen, it can be provided as a food taken daily, a health food taken as a supplement, or a functional food. The food according to the present invention is a food suitable for consumers who want to prevent physical strength from increasing or decreasing, increase exercise capacity, improve endurance, recover from fatigue, or improve carbohydrate metabolism, or those symptoms. Can be provided as a food suitable for the consumer, that is, for example, a so-called food for specified health use.

  Specific examples of such foods include, for example, beverages, powdered beverages, concentrated beverages, tablets, baked goods, soups, hamburgers, powdered foods, capsule foods, jelly, curry, bread, sausage, yogurt, cheese, chocolate, Although gum, jam, ice cream, etc. are mentioned, it does not restrict | limit in particular in these. In the food according to the present invention, the active ingredient according to the present invention can be blended into the food as it is or in the form of a composition.

  When the composition according to the present invention is used as a medicine, it can be used for treatment, prevention, or improvement of a disease or symptom that can be treated, prevented, or ameliorated by promoting storage of glycogen. By administering the composition according to the present invention to a patient, it is possible to achieve storage promotion of glycogen in tissues, and thereby, for example, improvement of carbohydrate metabolism of the patient can be achieved. Thus, according to the present invention, there is provided a method for promoting glycogen storage comprising administering to a mammal an effective amount of milk whey protein in promoting storage of glycogen. Here, the “effective amount” can be selected depending on the dose of the milk whey protein described above.

  In addition, the composition, food or pharmaceutical composition according to the present invention has a glycogen storage promoting action, a glycolytic enzyme and / or a gluconeogenic enzyme controlling action, further preventing physical strength from increasing or decreasing, enhancing exercise ability, It can be provided as a composition, food or pharmaceutical composition comprising milk whey protein as an active ingredient, which has been shown to improve endurance, recover from fatigue or improve carbohydrate metabolism.

  Examples of other components that can be used in the present invention include carbohydrates, proteins, amino acids, minerals, and / or vitamins. Here, examples of the carbohydrate include polysaccharides such as starch and corn starch, and other saccharides such as dextrin, sucrose, glucose and fructose. Here, the protein may be an animal protein, a vegetable protein, or a mixture thereof, and examples thereof include milk protein, soybean protein, egg protein and the like. As amino acids, leucine, isoleucine, valine, tryptophan, phenylalanine, lysine, threonine, methionine, histidine, and non-essential amino acids glutamine, glycine, alanine, serine, aspartic acid, glutamic acid, asparagine, arginine Cystine, tyrosine, proline, hydroxyproline, ornithine, taurine and the like. Moreover, as minerals, although it does not specifically limit, calcium, magnesium, iron, etc. are mentioned. Moreover, sodium, potassium, or other essential nutrient elements such as zinc, copper, chromium, selenium, manganese, and molybdenum can be used. In addition, vitamins are not particularly limited, but nutritionally essential vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, niacin, pantothenic acid, Examples thereof include folic acid and coenzyme Q10.

  In addition, as an acceptable carrier in the present invention, excipients, binders, diluents, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, Examples include preservatives such as magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, low melting point wax, cocoa butter, and the like. .

The composition according to the present invention can be produced, for example, as follows.
The composition according to the invention comprises, for example, excipients (eg lactose, sucrose, starch, mannitol), disintegrants (eg calcium carbonate, carboxymethylcellulose calcium), binders (eg pregelatinized starch, gum arabic, carboxymethylcellulose). , Polyvinyl pyrrolidone, hydroxypropyl cellulose), or a lubricant (for example, talc, magnesium stearate, polyethylene glycol 6000) is added to milk whey protein as an active ingredient and then compression-molded. In addition, it can be produced by coating by a method known per se for enteric or long-lasting purposes. As the coating agent, for example, ethyl cellulose, hydroxymethyl cellulose, polyoxyethylene glycol, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate and Eudragit (Rohm, Germany, methacrylic acid / acrylic acid copolymer) can be used.

  EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited to these Examples.

Example 1
According to a conventional method for promoting glycogen storage , a predetermined amount of the following components was collected, uniformly mixed, and compression molded to obtain tablets having a diameter of 7 mm and a tablet of 150 mg.
Milk whey protein 80 parts Glutamine 5 parts Valine 5 parts Leucine 7 parts Isoleucine 3 parts Corn starch 19 parts Crystalline cellulose 30 parts Magnesium stearate 1 part

Example 2
Food for promoting glycogen storage A predetermined amount of the following ingredients was collected and homogenized to produce a food according to the present invention.
Milk whey protein 90 parts Glutamine 2 parts Ferric pyrophosphate 1 part Corn starch 7 parts

Example 3
With food according tablet candy Example 2, in the following formulation was prepared tablet candy according to a conventional method.
Granulated sugar 52 parts Concentrated fruit juice 5 parts Citric acid 6 parts Fragrance 2 parts Emulsifier 3 parts Food of Example 2 32 parts

Test example 1
SD male rats (24 animals, 4 weeks old, SLC Japan) were preliminarily raised for about 1 week using a solid feed (CE-2, Clea Japan). Thereafter, these rats were divided into 3 groups (8 per group). For one group, a purified feed containing 25% casein as a dietary protein source is given (hereinafter referred to as “casein group”), and for another group, 25% milk whey protein is used as a dietary protein source. Containing purified feed (hereinafter referred to as “milk whey protein group”), and for other groups, purified feed containing 25% milk whey protein hydrolyzate as a dietary protein source (hereinafter referred to as “milk whey protein”). Hydrolyzate group ”), each of which was raised for 4 weeks. During the breeding period, food and water were ad libitum, and each group was subjected to treadmill exercise (exercise load for 30 minutes at a speed of 25 meters / minute) 5 times a week. Each group was fasted for 12 hours and then dissected under ether anesthesia. The liver and muscle (soleus muscle) were immediately removed and stored at −80 ° C. And the glycogen content in the tissue of each group was measured. For enzyme activity in the liver, the supernatant obtained by homogenizing the liver and centrifuging (100,000 G, 30 minutes) was used for the measurement. The results were as shown in Table 2 and FIG.

Table 2. Glycogen content (mg / g tissue)

Liver muscles
Milk whey protein group 10.65 2.93
Milk whey protein hydrolyzate group 10.50 2.92
Casein group 6.37 2.49

  As shown in Table 2, the milk whey protein group and the milk whey protein hydrolyzate group had higher glycogen stores in the liver and muscle than the casein group. In addition, as shown in FIG. 2, the glycolytic enzyme in the liver increased to 112% in the milk whey protein group compared to the casein group (the activity value in the casein group was assumed to be 100%). The phosphofructokinase activity decreased to 88% and the pyruvate kinase activity decreased to 71%. As for gluconeogenic enzymes in the liver, in the milk whey protein group, glucose 6-phosphatase significantly decreased the enzyme activity to 60%, and fructose 1,6-bisphosphatase increased the enzyme activity to 120%. Little change in phosphoenolpyruvate carboxykinase activity was observed.

Test example 2
SD male rats (32 animals, 4 weeks old, Japan SLC) were preliminarily raised for about 1 week using solid feed (CE-2, Japan Claire). Thereafter, these rats were divided into 2 groups (16 animals in each group). One group is given a purified feed containing 25% casein as a dietary protein source, and the other group is given a purified feed containing 25% milk whey protein as a dietary protein source (hereinafter, “ Milk whey protein group ”), and each was raised for 2 weeks. During the breeding period, food and water were ad libitum, and each group was allowed to swim 6 times a week (120 minutes exercise load). Each group was then further divided into two subgroups (8 each), one subgroup was dissected under ether anesthesia after 3 hours of fasting, the other subgroup was fasted for 3 hours, Immediately after the exercise load of 180 minutes, it was dissected under ether anesthesia. For each group, the liver and muscle (soleus muscle) were removed and stored at −80 ° C. Then, the glycogen content in the tissue was measured. The results are shown in Table 3.

Table 3. Glycogen content (mg / g tissue)
Liver muscles
Before exercise After exercise Before exercise After exercise
Milk whey protein group 87.4 37.6 5.23 3.29
Casein group (control group) 63.7 26.0 4.21 2.31

  As shown in Table 3, the amount of liver and muscle glycogen in the milk whey protein group was higher than that in the casein group before and after exercise.

FIG. 1 is a schematic diagram of the main pathways in glycolysis and gluconeogenesis. 2 is a graph showing enzyme activity in rat liver in Test Example 1. FIG.

Claims (11)

  A composition used for promoting storage of glycogen, comprising milk whey protein as an active ingredient.   A composition used for controlling glycolytic enzymes and / or gluconeogenic enzymes, comprising milk whey protein as an active ingredient.   The composition according to claim 1 or 2, which is used for prevention of enhancement or decrease of physical strength, enhancement of exercise ability, improvement of endurance, recovery from fatigue or improvement of carbohydrate metabolism.   A food used for promoting storage of glycogen, comprising the active ingredient according to claim 1.   The food according to claim 4, which is used to prevent physical strength from increasing or decreasing, to increase exercise capacity, to improve endurance, to recover from fatigue, or to improve carbohydrate metabolism.   The food according to claim 4 or 5, which is a health food, a functional food, a food for specified health use, or a food for a sick person.   The food according to any one of claims 4 to 6, which is provided in the form of a beverage.     A pharmaceutical composition used for promoting storage of glycogen, comprising the active ingredient according to claim 1.   Use of the active ingredient according to claim 1 or 2 for producing a composition used for promoting storage of glycogen.   Use of the active ingredient according to claim 1 or 2 for producing a food used for promoting storage of glycogen.   Use of the active ingredient according to claim 1 for producing a pharmaceutical composition used for promoting storage of glycogen.

Images