KR100523354B1 - Pharmaceutical composition or functional foods for suppressing fatigue in exercise demanding endurance and for improving immune function after exercise - Google Patents

Abstract

The present invention relates to a pharmaceutical composition or functional food containing amino acids and sugars as active ingredients to improve endurance exercise performance, as well as to suppress fatigue during endurance exercise and to improve immune function after exercise. More specifically, the present invention includes ornithine α-ketoglutarate (OKG), a compound of ornithine and α-ketoglutarate with branched chain amino acids (BCAAs), to improve endurance performance. Of course, the present invention provides a pharmaceutical composition or functional food for suppressing fatigue during endurance exercise and improving immune function after exercise.

Such a pharmaceutical composition or functional food of the present invention significantly inhibits the increase in blood concentrations of ammonia and lactic acid, which are peripheral and central fatigue-inducing substances during exhaustive endurance, during and immediately after exercise to improve exercise performance and faster fatigue recovery ability. In addition to preventing the phenomenon of a significant decrease in the number of immune cells after stabilization after exercise, it is possible to treat or prevent a decrease in immune function during the recovery phase. Will be widely used as.

Description

PHARMACEUTICAL COMPOSITION OR FUNCTIONAL FOODS FOR SUPPRESSING FATIGUE IN EXERCISE DEMANDING ENDURANCE AND FOR IMPROVING IMMUNE FUNCTION AFTER EXERCISE}

The present invention relates to a pharmaceutical composition or a functional food for improving endurance exercise performance as well as for suppressing fatigue during endurance exercise and improving immune function after exercise.

In endurance sports such as marathon, athletes often reach extreme fatigue conditions such as decreased attention, malaise, and helplessness in the late stages (32-38 km). These causes of physiological and biochemical changes in active muscles Of course, it is also closely related to changes in homeostasis of the central nervous system.

Specifically, one of the factors that causes metabolic changes in the homeostasis of the central nervous system is reported to be due to an increase in the concentration of serotonin in the brain due to changes in the composition of plasma amino acids, which occur mainly when glycogen is stored in the muscle. [Newsholme, EA, Acworth, IN and Blomtrand, E. (1987) Amino acids, brain transmitters and a functional link between muscle and brain that is important in sustained exercise. In: Benzi G (ed), Advances in myochemistry, John Libb Eurotext, London, 127-138.

The reason why the increase in the concentration of brain serotonin, a neurotransmitter of the central nervous system, causes central fatigue during endurance sports such as marathon is due to the action that decreases drowsiness and exercise performance which is characteristic of brain serotonin. That is because it induces drowsiness and reduces the activity of the exercise.

Since the amount of brain tryptophan that synthesizes brain serotonin is an essential amino acid, it depends on the amount of free tryptophan in the plasma that enters the brain.

However, the amino acid carriers involved in the process of plasma free tryptophan entering the brain via the blood brain-barrier (System L) are branched chain amino acids (leucine; leucine, isoleucine; isoleucine, valine; Because they can also carry valine, tyrosine, and phenylalanine, these amino acids cause a race condition when plasma free tryptophan enters the brain.

Conditions in which brain tryptophan concentrations can be increased in such situations are relative to those of other amino acids in which plasma free tryptophan concentrations are competing (ie, plasma free tryptophan / branched chain amino acids (BCAA) + tyrosine + phenylalanine). In the endurance movement, this phenomenon is caused by two factors.

First is an increase in the concentration of plasma free tryptophan.

About 80-90% of tryptophan present in plasma is present in relatively weak binding form with albumin, and the rest is in unbound free form.

However, if the concentration of free fatty acids in plasma increases due to the increase of lipolysis during endurance exercise, albumin, which has been combined with tryptophan, has a strong binding property with free fatty acids, which increases the concentration of free tryptophan in plasma. do.

In this respect, US researchers (1992) [Wagemnakers, A.J.M. (1992) Role of amino acids and ammonia in mechani are described in fatique. In: Muscle fatigue mechanism in exercise and training. Marconnet. P., Komi. P.V., Saltin. B, Sejersted. O. M (eds). Med. Sport. Sci. Basel, Karger. Vol 34, 69-86; Wilson, W.M. and Maughan, RJ (1992) Evidence for a possible role of 5-hydroxytrypamine in the genesis of fatigue in man: administration of paroxetine, a 5-HT re-uptake inhibitor, reduces the capacity to perform prolonged exercise, E, perimental Physion. , 77, 921-924], a method for suppressing the increase in the concentration of plasma free fatty acids during endurance exercise, in which healthy people were given a carbohydrate-based drink during exercise, resulting in plasma free tryptophan throughout the exercise period. It was said that the concentration ratio of the branched chain amino acid to the low was maintained.

Based on these findings, they suggest that carbohydrate administration can reduce central fatigue during endurance exercise.

Second is the decrease in the concentration of plasma branched amino acids (BCAAs).

Late stages of endurance, such as marathon, are the days when glycogen stored in muscles is depleted, which increases the concentration of amino acids in the plasma because of an increase in proteolytic reactions in the muscles.

In particular, in contrast to most plasma amino acids used in the liver, branched chain amino acids are primarily used for energy supply in active muscles, so the oxidation rate of branched chain amino acids in active muscles during endurance exercise increases the degradation reaction of active muscle proteins. In the case of increasing the production rate of branched chain amino acids, the concentration of plasma branched chain amino acids is reduced.

Moreover, since plasma tyrosine and phenylalanine show little concentration change during endurance exercise, eventually increased plasma free tryptophan (ie, an increase in the plasma free tryptophan / branched amino acid concentration ratio) passes through the blood-brain-brain membrane by the amino acid carrier. It becomes easier to do so, which increases the concentration of brain tryptophan and increases the concentration of brain serotonin.

In this regard, a method of administering branched chain amino acids during endurance exercise may be considered to suppress an increase in the ratio of branched chain amino acids to plasma free tryptophan concentration due to a decrease in the concentration of plasma branched chain amino acids during endurance exercise.

In this regard, researchers in Sweden and the United Kingdom (1992) [Davis, J.M., Bailey, S.P., Woods, J.A., Galiano, F.J., Hamilton, M.T., Hamilton, M.T. and Bartoli, W. P. (1992) Effects of carbohydrate feedings on plasma free try ptophan and branched-chain amino acids during prolonged cycling, Eur. J. Appl. Physiol., 65, 513-519; Newsholme, E.A., Bolmstrand, E. and Ekblom, B. (1992) Glutamine metalbolism in lymphcytes: its biochemical, physiological and clinical importance, Q. J. Expt. Physiol., 70. 473-489] developed a drink consisting mainly of branched amino acids, according to which, according to the results, the athletes who participated in the marathon and cross-country competition were given a drink containing the branched amino acid as the main ingredient. He said that with the shortening of time, mental fatigue was reduced.

However, if the above results are examined in detail, the following problems can be found. First, looking at the results of US researchers, one can find that the effect of increasing the concentration of insulin from carbohydrate administration has not been observed more closely.

Administration of carbohydrates may have the effect of decreasing the concentration of plasma free tryptophan, since the concentration of insulin reduces the concentration of plasma free fatty acids.

In addition to this effect, however, increasing insulin concentrations also significantly reduce the concentrations of branched chain amino acids, tyrosine, phenylalanine, which result in a race condition in the entry of plasma free tryptophan into the brain.

Since this, in turn, increases the concentration ratio for other amino acids that compete with free tryptophan in the plasma, a relatively increased concentration of free plasma tryptophan may therefore increase the concentration of brain tryptophan.

Therefore, the method of carbohydrate administration has the positive effect of providing blood glucose as an energy source during endurance exercise, while suppressing the increase in the concentration of brain tryptophan, a precursor of brain serotonin, which acts as part of the cause of central fatigue. Or it can be seen that it is not suitable to reduce.

In addition, the method of administering branched chain amino acids proposed by researchers in Sweden and the United Kingdom is largely due to the metabolic properties of branched chain amino acids, in addition to the positive effect of increasing the concentration of plasma branched chain amino acids that are reduced during endurance exercise. Two types of problems can be brought about.

First, the oxidative process of the branched chain amino acids in the active muscles during endogenous exercise, which leads to the depletion of muscle glycogen, is significantly activated. In the aminotransfer reaction, the first stage of the branched chain amino acid oxidation reaction, 2-oxogle, an intermediate product of the Krebs cycle Rutarate (2-oxoglutarate) is used as an amino group receptor.

Therefore, if the concentration of branched chain amino acids in plasma decreased due to increased use of active muscles in endogenous exercise at the level of endurance exercise resulting in muscle glycogen depletion, the oxidation process of branched chain amino acids in skeletal muscle is further increased. It will be activated.

This metabolic process further reduces the concentration of 2-oxoglutarate and leads to depletion, thus inhibiting the production of adenosine triphospate (ATP), an energy source required for the contraction of active muscles during endurance exercise. Eventually it will have a negative effect on the performance of the endurance movement.

Second, depletion of 2-oxoglutarate can also deplete the concentration of glutamate, making it difficult to convert and remove ammonia, a toxic substance in vivo produced during the oxidation of branched chain amino acids, into glutamine during endurance exercise. .

Increasing the concentration of ammonia produced during the oxidation of branched chain amino acids will act as another form of fatigue inducing metabolism in active muscles and the central nervous system.

As described above, the administration of the branched chain amino acid has a positive effect of suppressing the increase in the ratio of the branched chain amino acid to plasma free tryptophan during endurance exercise, thereby reducing the concentration of brain serotonin, which is the cause of central fatigue. It inhibits the production of adenosine triphosphate (ATP), which is an energy source necessary for the contraction of active muscles during exercise, and thus does not have an effect on endurance exercise, and may also increase the concentration of ammonia known as a toxic substance in vivo. It can be said to have.

Finally, it is also important to secure the problem of having a high infection frequency due to a decrease in the number of immune cells and impaired immune function after exhaustive endurance exercise.

Accordingly, the present inventors can effectively improve endurance exercise performance while suppressing the concentration of cerebral serotonin, which is the cause of central fatigue during endurance exercise that causes muscle glycogen depletion, and can suppress impaired immune function after exercise. Discovered to complete the present invention.

In an aspect, the present invention provides a molecular formula of C ₅ H ₆ O ₅ (C ₅ H ₁₂ N ₂ O ₂ ) ₂ .2H ₂ O together with a branched chain amino acid (BCAA). Provided is a pharmaceutical composition comprising ornithine α-ketoglutarate (OKG), which is a composite of ornithine and α-ketoglutarate represented by Formula 1 below.

In a preferred embodiment, the present invention comprises a composite of ornithine and alpha-ketoglutarate (OKG) with leucine, isoleucine, valine as active ingredients, effectively enhancing endurance exercise performance and inhibiting brain serotonin concentrations It provides a pharmaceutical composition that can suppress immune function damage after exercise.

Formulation of such a pharmaceutical composition is preferably an oral administration solution prepared by dissolving the active ingredient in purified water, but may be prepared and administered in a solid oral preparation, that is, a tablet, a capsule, a granule, and the like.

In a more preferred embodiment, the invention is endurance containing a branched chain amino acid mixture consisting of 35% leucine, 25% isoleucine and 40% valine, and an OKG compound consisting of 64% ornithine and 36% alpha-ketoglutarate. The present invention provides a pharmaceutical composition that effectively improves exercise performance, suppresses brain serotonin concentration, and inhibits impaired immune function after exercise.

In such a pharmaceutical composition, the branched chain amino acid mixture and the OKG compound are preferably contained in an equal ratio.

Such pharmaceutical compositions may optionally contain sweetening agents. The sweetener may contain aspartame, cyclate, saccharin, and the like, and the sweetener may be included in an amount of about 15 mg based on 100 ml of the total pharmaceutical composition.

In another aspect, the present invention also provides a functional food comprising ornithine α-ketoglutarate (OKG), which is a composite of ornithine and α-ketoglutarate, together with a branched chain amino acid (BCAA).

In a preferred embodiment, the present invention comprises a composite of ornithine and alpha-ketoglutarate with leucine, isoleucine, valine as functional ingredients, effectively enhancing endurance exercise performance, inhibiting brain serotonin concentration and performing exercise It provides a functional food that can suppress immune impairment.

Such a functional food is preferably a beverage prepared by dissolving the functional ingredient in purified water, but may be prepared in various product forms such as gum, jelly, candy, and powder.

In a more preferred embodiment, the invention is endurance containing a branched chain amino acid mixture consisting of 35% leucine, 25% isoleucine and 40% valine, and an OKG compound consisting of 64% ornithine and 36% alpha-ketoglutarate. It provides a functional food that effectively improves exercise performance, suppresses brain serotonin concentration, and suppresses immune function impairment after exercise.

In such a functional food, it is preferable that a branched chain amino acid mixture and an OKG compound are contained in equal ratio.

Such functional foods may contain various sweeteners as needed. The sweetener may contain aspartame, cyclate, saccharin, and the like, and the content of the sweetener may be included in an amount of about 15 mg based on 100 ml of the total beverage composition.

BCAA (branched chain amino acids-leucine, valine, isoleucine) is an essential amino acid, and OKG (ornitine α-ketoglutarate) is a compound of ornithine and α-ketoglutarate, both of which are commercially available formulations. Each is already known as a supplement that plays a role in preventing muscle breakdown, reducing fatigue awareness, hormonal precursors, and stimulating growth hormone secretion, but suggests or suggests mixed doses of OKG as a solution to BCAA and its solution. It has not been done.

As described above, branched-chain amino acid (BCAA) administration was thought to relatively reduce the influx of serotonin precursor free-tryptophan into the brain, resulting in inhibition of serotonin production, but occurred during BCAA metabolism. Ammonia causes the degeneration of the mesentery, which increases the influx of free tryptophan into the brain. As a result, BCAA administration during endurance exercise does not reduce the increase in serotonin, a substance that causes central fatigue.

Therefore, the present inventors consider the administration of OKG as a way to lower the ammonia concentration generated during endurance exercise.

OKG administration can raise both glutamate and ornithine levels in the body at the same time, and these two substances are considered to be suitable methods to remove ammonia that occurs during exercise as a biological substance. It has been shown to lower the concentration of free tryptophan and serotonin, precursors of ammonia, serotonin, and to reduce central fatigue and at the same time alpha-ketogluta, an intermediate metabolite of the TCA circuit by leucine, valine, isoleucine and OKG as energy sources. Increasing the concentration of α-ketoglutarate has been found to increase athletic performance, and alpha-ketoglutarate is also converted to glutamate in the body, which is converted back to glutamine. This not only increases motor performance, but also affects lymphocyte proliferation, macrophage phagocytosis and the production of major cytokines, interleukin-1 and interleukin-2, which play an important role in immune function. It has been found that a significant decrease in immune function is suppressed.

The characteristic of ornithine alpha-ketoglutarate used in the present invention is that it is harmless to the human body because all of its components are present in vivo, stable in aqueous solution, and metabolized quickly because of good cell permeability. It has the advantage of being able to efficiently produce glutamate in vivo.

The effects of ornithine alpha-ketoglutarate on exercise can be summarized in the following four ways.

First, since ornithine alpha-ketoglutarate produces glutamate in vivo, 2-oxoglutarate, an intermediate product of the Krebs cycle depleted by the oxidative activity of branched chain amino acids, is essentially from glutamate to the Krebs cycle. Because it can be supplied through the existing supplementary reaction system, it can play a role in supplementing the inhibitory effect on aerobic adenosine triphosphate (ATP) production caused by the oxidative activity of branched chain amino acids at the time when muscle glycogen is depleted. .

Second, glutamate produced by the administration of ornithine alpha-ketoglutarate can convert ammonia produced by the administration of branched chain amino acids during endurance exercise into the form of glutamine through the glutamine synthetase reaction. Ornithine, a component of toglutarate, is an intermediate product of the urea cycle and can also convert increased ammonia to urea form as a reactant of the ornithine carbamoyl transferase reaction, a step in determining the rate of reaction of urea production.

Third, glutamate produced by ornithine alpha-ketoglutarate administration increases the activity of alanine iminotransferase reactions, which induces alanine-producing reactions from acetic acid in the process under anaerobic conditions. The amount of lactic acid produced in can be reduced, and the accumulated lactic acid can be treated by converting it to acetic acid by lactic acid dehydrogenase reaction.

This is based on the fact that because the reactions catalyzed by alanine aminotransferase and lactic acid dehydrogenase are almost equilibrium reactions, the direction of the reaction can be reversed simply by changing the concentration of reactants or products by the law of mass action.

This action can reduce the concentration of hydrogen ions, which are known to be the main cause of fatigue of active muscles, in anoxic conditions, and thus increase the concentration of hydrogen ions, which reduces fatigue of active muscles due to the increase of lactic acid during endurance exercise. Can also be performed.

Fourth, glutamate produced by ornithine alpha-ketoglutarate administration can increase the concentration of glutamine, which decreases below physiological levels during endurance exercise.

Later in endurance exercise, glutamine levels, along with glutamate levels, are significantly reduced. Glutamine plays an essential role in the proliferation of lymphocytes, which play a major role in the immune system in vivo, and as an energy source and also in macrophages. do.

In other words, an increase in the upper respiratory tract infection rate such as endurance exercise such as marathon or triathlon and cold after the excessive training is due to a decrease in the concentration of plasma glutamine, thereby reducing immune function.

Therefore, glutamate produced by ornithine alpha-ketoglutarate administration has the advantage of serving as a good precursor of glutamine, which can help athletes recover from fatigue, prevent immune function and maintain their condition after endurance exercise. .

Hereinafter, the present invention will be described with reference to specific examples and test examples, and the present invention is not limited only to these examples and test examples, and the% described herein refers to a content%.

<Example 1>

      OKG: Ornithine 64%

      (5g) Alpha-Ketoglutarate 36%

      Fragrance: Aspartame 15mg / 100ml

      500ml of purified water

<Example 2>

      BCAA: Leucine 35%

      (78mg / kg) isoleucine 25%

                Valine 40%

     OKG: Ornithine 64%

    (78mg / kg) alpha-ketoglutarate 36%

     Fragrance: Aspartame 15mg / 100ml

     500ml of purified water

 <Example 3>

     OKG: Ornithine 64%

    (78mg / kg) alpha-ketoglutarate 36%

     Fragrance: Aspartame 75mg / 500ml

Experimental results of oral administration of the complex preparation of the present invention prepared as described above were investigated.

<Test Example 1>

Effects of ornithine α-ketoglutarate administration on blood ammonia levels during submaximal exercise:

Ten male college students in Y-university who were physically healthy were subjected to submaximal exercise using a bicycle ergometer for 20 minutes with an intensity of 70% VO ₂ max. 300 ml) and orally administered. The experimental conditions for OKG and placebo were the same, and randomized treatment was performed by crossing OKG and placebo. After the first experiment, the second experiment was conducted at a weekly interval. Blood sampling was performed by inserting a catheter into the forearm vein of the subject. The catheter was inserted before blood collection.The blood collection time was just before OKG administration, 50 minutes after OKG administration, 5 minutes after exercise start, 10 minutes 15 minutes, 20 minutes (just after exercise), 10 minutes recovery period, and 10 ml each for 30 minutes. Multiple blood collection was performed (in FIGS. 1A to 1E, the blood collection periods are shown as rest1, rest2, ex1, ex2, ex3, ex4, rc1 and rc3, respectively). Changes in ammonia, blood glutamate, blood glutamine, blood ornithine and heart rate in response to OKG were obtained.

OKG administration was found to have a significant decrease in ammonia concentrations compared to placebo administration (p <0.05) (see FIG. 1A). In addition, blood glutamate (FIG. 1B), glutamine in blood (FIG. 1C), and blood ornithine concentration (FIG. 1D) also showed that the administration of OKG increased to a significant level. Changes in heart rate did not show a difference between OKG administration and placebo administration (FIG. 1E).

These results confirm that OKG administration can suppress the increase of blood ammonia concentration during submaximal exercise.

By observing the effect of OKG administration on blood ammonia levels during submaximal exercise, we experimentally examined whether OKG is effective in reducing blood ammonia concentrations that cause fatigue.

1. The blood ammonia level was lower in the OKG group than in the placebo group, and statistically significant differences were found.

2. Plasma glutamate concentration was higher in the OKG group than in the placebo group, and statistically significant differences were found.

3. Plasma glutamine concentration was higher in the OKG group than in the placebo group, and statistically significant differences were found.

4. Plasma ornithine concentration was higher in the OKG group than in the placebo group, and statistically significant differences were found.

5. Changes in heart rate were similar in both OKG and placebo groups.

In conclusion, it was confirmed that the administration of OKG during submaximal exercise effectively reduced ammonia concentration, thereby reducing fatigue and improving athletic performance.

<Test Example 2>

Effects of Branched Chain Amino Acids (BCAA) and Ornithine α-Ketoglutarate Combination on Central Fatigue during Endurance Exercise:

Nine cyclists in medically disease-free high school were trained to exhaustion using a bicycle ergometer with a strength of 70% VO ₂ max of each subject and dissolved in 500 ml of reverse osmosis water (valine 40) %, Leucine 35%, Isoleucine 25%), OKG (64% ornithine, 36% α-ketoglutarate) were orally administered 78 mg / kg body weight of each subject. The experimental conditions for the BCAA + OKG complex and placebo administrations were the same, and a randomized treatment was used for the BCAA + OKG complex and placebo administrations. Blood collection time was collected 5 times before the administration of each formulation, 50 minutes after the administration of the formulation, 30 minutes during exercise, 30 minutes during exhaustion, 30 minutes during the recovery period (Fig. 2a to 2f, respectively, rest1, rest2, exe30, post and rec30). Blood ammonia, lactic acid, serotonin and BCKA concentrations (branched keto acids), BCAA concentrations, blood amino acids ornithine, glutamine, glutamate, alanine, tryptophan, glucose, subjective fatigue and endurance exercise As a result of analyzing the ability, the following results were obtained.

When BCAA + OKG mixed administration, blood ammonia, lactic acid, serotonin concentration was significantly reduced compared to placebo administration (p <0.05) (Fig. 2a). Blood BCKA (FIG. 2B), blood BCAA (FIG. 2C) and blood amino acids (FIG. 2D), namely ornithine, glutamate, glutamine, alanine, tryptophan concentrations, were also found to be significantly increased upon BCAA + OKG combination administration.

These results confirmed that BCAA + OKG complex administration can improve the serotonin and ammonia concentration and endurance performance during endurance exercise.

Experimental study was conducted to investigate the effects of BCAA and OKG, which can increase the concentration of glutamate in the body, on blood ammonia and endurance exercise performance. The same conclusion was obtained.

1. Plasma ammonia concentrations were found to be statistically significant (p <.05) in the BCAA + OKG mixed administration compared to placebo.

2. The blood lactate concentration was lower in BCAA + OKG compared to placebo and statistically significant difference (p <.05) was found.

3. Serum serotonin levels were lower in BCAA + OKG compared to placebo and statistically significant differences (p <.05) were found.

4. Serum BCKA concentration was higher in BCAA + OKG compared with placebo, but no statistically significant difference was found.

5. The serum BCAA level was higher in BCAA + OKG administration compared to placebo and statistically significant difference (p <.05) was found.

6. Serum ornithine, glutamine, and glutamate concentrations were higher in BCAA + OKG compared to placebo and statistically significant differences (p <.05) were found.

7. Serum alanine concentration was higher in BCAA + OKG compared with placebo, but no statistically significant difference was found.

8. Tryptophan concentration was lower in the BCAA + OKG group compared to the placebo group, and no statistically significant difference was found.

9. The blood glucose level was slightly lower in the BCAA + OKG mixed group compared to the placebo group, but no statistically significant difference was found (FIG. 2E).

10. Subjective exercise intensity (RPE) and exercise time were lower in BCAA + OKG compared to placebo when assessed based on a chart of subjects' self-fatigue during exercise on a subjective exercise intensity (RPE scale). There was no statistically significant difference. There was no significant difference in exercise performance time, but BCAA + OKG mixed administration was found to be improved compared to placebo administration (Fig. 2f).

Taken together, it was confirmed that BCAA + OKG mixed administration during endurance exercise can suppress the increase of serotonin and ammonia concentrations, which are central fatigue factors, and further improve exercise performance.

<Test Example 3>

Effect of ornithine α-ketoglutarate administration on immune function after endurance exercise:

Ten athletes who were physically healthy and attending college were subjected to endurance exercise using bicycle ergometer for 90 minutes at 70% VO ₂ max intensity, and dissolved OKG in reverse osmosis water (500ml). By oral administration. The experimental conditions for OKG and placebo were the same, and randomized treatment was performed by crossing OKG and placebo. After the first experiment, the second experiment was conducted at a weekly interval. The test subjects arrived at the laboratory 1 hour before the start of the experiment in a state of fasting and rested for 20 minutes while lying down, and then administered 200ml of the dissolved solution in reverse osmosis water, followed by endurance exercise after 60 minutes. In addition, 300 ml of each of the above formulations was administered immediately after exercise. Blood sampling was performed by inserting a catheter into the forearm vein of the subject. The catheter was inserted before blood collection, and the blood collection time was taken 6 times at the time of immediately before the administration of the sanction, 50 minutes after the administration of OKG, 90 minutes after the start of exercise (right after the exercise), 30 minutes, 60 minutes, and 120 minutes during the recovery period (FIG. 3A). 3 to 3d show the blood collection periods as rest1, rest2, post, rec.30, rec.60 and rec.120, respectively). Interleukin-1, leukocytes, neutrophils and lymphocytes following OKG administration were analyzed.

The number of neutrophils, leukocytes, and interleukin-1 was significantly increased at 30 and 60 minutes after endurance exercise compared to placebo, and lymphocytes were increased at all levels. (p <0.05) (see FIGS. 3A, 3B, 3C and 3D, respectively).

These results confirm that OKG administration can suppress the deterioration of immune function during recovery phase after exhaustive endurance exercise. The results of experimental investigations on the effects of OKG on the levels of interleukin-1, leukocytes, neutrophils and lymphocytes after administration of OKG as a way to suppress the decrease in immune cell count and immune function decrease after exhaustive endurance exercise were as follows. Got.

1. The number of interleukin-1 in blood was statistically significant (p <.05) in OKG administration at 30 and 60 minutes of recovery compared to placebo.

2. Serum leukocyte counts were significantly (p <.05) increased in the 30 and 60 minutes of recovery compared to placebo.

3. The neutrophil counts in the blood were increased significantly (p <.05) in the 30 and 60 minutes of recovery compared to placebo.

4. Lymphocyte counts in the blood were increased significantly (p <.05) at 30, 60, and 120 minutes of recovery compared to placebo.

Taken together, it was confirmed that OKG administration during exhaustive endurance exercise significantly improved immune cell number and immune function during recovery phase after exercise and helped athletes maintain their physical condition.

According to the present invention as described above, it can be seen that administration of OKG during submaximal exercise effectively reduces ammonia concentration, thereby reducing fatigue and improving athletic performance, and BCAA + OKG mixed administration during endurance exercise is central. It can be confirmed that it can suppress the increase of serotonin and ammonia concentrations, which can contribute to the improvement of exercise performance, and that OKG administration during exhaustive endurance exercise significantly reduces immune cell count and immune function in the recovery phase after exercise. To improve their performance and help keep players in good shape.

Figure 1a is a graph showing the change in concentration (μmol / L) of blood ammonia by OKG administration during submaximal exercise.

Figure 1b is a graph showing changes in blood glutamate concentration (μmol / L) by OKG administration during submaximal exercise.

Figure 1c is a graph showing the change in blood glutamine concentration (μmol / L) by OKG administration during submaximal exercise.

1D is a graph depicting changes in ornithine concentration (μmol / L) in blood by OKG administration during submaximal exercise.

1E is a graph showing heart rate change (heart rate / minute) by OKG administration during submaximal exercise.

Figure 2a shows the ammonia (μmol / L), lactic acid (mmol / L) and serotonin (ng / ml) of blood by the combined administration of branched chain amino acids (BCAA) and OKG according to the present invention during endurance exercise using the bicycle ergometer Graph showing concentration change (* p <0.05).

Figure 2b is a branched chain amino acid (BCAA) according to the invention during endurance exercise using the bicycle ergometer blood branched chain keto acid (BCKA), that is α-ketoisocaprate (μmol / L), Graph showing the change in concentration of α-keto-β-methylvalerate (μmol / L) and α-ketoisovalerate (μmol / L) (* p <0.05, ** p <0.01).

Figure 2c is a branched chain amino acid (BCAA) according to the invention during endurance exercise using the bicycle ergometer, blood branched chain amino acids, ie leucine (μmol / L), isoleucine (μmol / L) and valine Graph showing concentration change in (μmol / L) (* p <0.05, ** p <0.01).

Figure 2d is a blood amino acid, ornithine (μmol / L), glutamine (μmol / L), glutamate (μmol) by the combination administration of branched chain amino acids (BCAA) and OKG according to the present invention during endurance exercise using the bicycle ergometer / L), a graph depicting the change in concentration of alanine (μmol / L) and tryptophan (μmol / L) (* p <0.05, ** p <0.01).

Figure 2e is a graph showing the change in blood glucose concentration by the combined administration of branched chain amino acids (BCAA) and OKG according to the present invention during endurance exercise using the bicycle ergometer.

Figure 2f is a graph showing the subjective fatigue change by the combined administration of branched chain amino acids (BCAA) and OKG according to the present invention during endurance exercise using the bicycle ergometer.

Figure 3a is a graph showing the change in concentration (pg / ml) of blood interleukin-1 (IL-1), one of the immune cells by OKG administration during endurance exercise using the bicycle ergometer (*, p <0.05).

Figure 3b is a graph showing the change in blood leukocyte count (x 10 ³ / μl) of one of the immune cells by OKG administration during endurance exercise using the bicycle ergometer (*, p <0.05; **, p <0.01) .

Figure 3c is a graph (**, p <0.01) showing the change in the number of blood neutrophils (x 10 ³ / μl) of one of the immune cells by OKG administration during endurance exercise using the bicycle ergometer.

FIG. 3D is a graph depicting changes in blood lymphocyte count (x 10 ³ / μl), one of immune cells by OKG administration during endurance exercise using bicycle ergometer (*, p <0.05; **, p <0.01; ***, p <0.001).

Claims (18)

A compound of ornithine and α-ketoglutarate represented by the following Chemical Formula 1 having a molecular formula of C ₅ H ₆ O ₅ (C ₅ H ₁₂ N ₂ O ₂ ) ₂ · 2H ₂ O with a branched chain amino acid (BCAA) Includes phosphorus ornithine α-ketoglutarate (OKG), The branched chain amino acid (BCAA) comprises leucine 35%, isoleucine 25%, valine 40%, The OKG consists of 64% ornithine and 36% alpha-ketoglutarate, A pharmaceutical composition for improving endurance exercise performance, as well as suppressing fatigue during endurance exercise and improving immune function after exercise. Formula 1 delete delete delete The pharmaceutical composition according to claim 1, wherein the branched chain amino acid (BCAA) and OKG are included in an equal ratio. The pharmaceutical composition according to claim 1, wherein the composition is in the form of a liquid, tablet, capsule, or granule for oral administration. The pharmaceutical composition of claim 1, further comprising a sweetener. 8. The pharmaceutical composition of claim 7, wherein the sweetener is aspartame. The pharmaceutical composition according to claim 8, wherein the aspartame is included in an amount of 15 mg / 100 ml of the composition. Along with the branched chain amino acid (BCAA), the molecular formula is C ₅ H ₆ O ₅ (C ₅ H ₁₂ N ₂ O ₂ ) ₂ · 2H ₂ O and is a compound of ornithine and α-ketoglutarate represented by the following Chemical Formula 1 Ornithine α-ketoglutarate (OKG), The branched chain amino acid (BCAA) comprises leucine 35%, isoleucine 25%, valine 40%, The OKG consists of 64% ornithine and 36% alpha-ketoglutarate, Functional food for improving endurance exercise performance, as well as suppressing fatigue during endurance exercise and improving immunity after exercise. Formula 1 delete delete delete The functional food according to claim 10, wherein the branched chain amino acid (BCAA) and OKG are included in an equal ratio. 11. The functional food according to claim 10, wherein the food is any one of a sports drink, gum, jelly, candy, and powder. 11. A functional food according to claim 10, further comprising a sweetener. The functional food according to claim 16, wherein the sweetener comprises aspartame, cyclate or saccharin. 18. The functional food according to claim 17, wherein the sweetener is contained in an amount of 15 mg / 100 ml of composition.