阅读说明：本技术 氨代谢促进剂 (Ammonia metabolism promoter ) 是由 莲村卓广 陈姝 太田宣康 峰岸庆彦 大塚敦子 小林明美 于 2018-05-18 设计创作，主要内容包括：本发明提供一种具有优异的氨代谢改善作用、持久力提高、对抗疲劳等有效的原料。以儿茶素类和鸟氨酸为有效成分的氨代谢促进剂。以儿茶素类和鸟氨酸为有效成分的持久力提高剂。以儿茶素类和鸟氨酸为有效成分的抗疲劳剂。以儿茶素类和鸟氨酸为有效成分的运动中的血糖值降低的抑制剂。以儿茶素类和鸟氨酸为有效成分的从因运动导致的血糖值降低的恢复的促进剂。以儿茶素类和鸟氨酸为有效成分的运动中的肌肉糖原降低的抑制剂。以儿茶素类和鸟氨酸为有效成分的肌肉持久力提高剂。以儿茶素类和鸟氨酸为有效成分的高氨血症、肝性脑病或慢性疲劳综合征的预防或改善剂。(The present invention provides a raw material which has an excellent ammonia metabolism improving effect, an improved endurance, and an effect of resisting fatigue. An ammonia metabolism promoter contains catechin and ornithine as effective components. Endurance improver containing catechin and ornithine as effective components. An antifatigue agent contains catechin and ornithine as effective components. An inhibitor for reducing blood glucose level in exercise containing catechins and ornithine as active ingredients. A promoter for recovering from blood glucose level decrease due to exercise contains catechin and ornithine as effective components. An agent for inhibiting muscle glycogen decrease in exercise contains catechin and ornithine as effective components. A muscle endurance improver contains catechin and ornithine as effective components. A preventive or ameliorating agent for hyperammonemia, hepatic encephalopathy or chronic fatigue syndrome, which contains catechin and ornithine as active ingredients.)

1. An ammonia metabolism accelerator, characterized in that:

comprises catechin and ornithine as effective components.

2. A endurance improver characterized by:

comprises catechin and ornithine as effective components.

3. An anti-fatigue agent characterized by:

comprises catechin and ornithine as effective components.

4. An inhibitor for lowering blood glucose level due to exercise, characterized in that:

comprises catechin and ornithine as effective components.

5. A promoter for recovery from a decrease in blood glucose level due to exercise, which is characterized by:

comprises catechin and ornithine as effective components.

6. An inhibitor of muscle glycogen reduction due to exercise, characterized in that:

comprises catechin and ornithine as effective components.

7. A muscle endurance improver characterized by:

comprises catechin and ornithine as effective components.

8. The agent according to any one of claims 1 to 7, wherein:

the mass ratio of catechins to ornithine is 1: 0.1-10.

9. Use of catechins and ornithine for the manufacture of an ammonia metabolism promoter.

10. Use of catechins and ornithine for the manufacture of an endurance improving agent.

11. Use of catechins and ornithine for the manufacture of an anti-fatigue agent.

12. Use of catechins and ornithine for producing an inhibitor for lowering blood glucose level due to exercise.

13. Use of catechins and ornithine for producing a promoter for recovery from a decrease in blood glucose level due to exercise.

14. Use of catechins and ornithine for the manufacture of an inhibitor of muscle glycogen reduction due to exercise.

15. Use of catechins and ornithine for the manufacture of a promoter for recovery from muscle glycogen reduction due to exercise.

16. Use of catechins and ornithine for the manufacture of a muscle endurance improver.

17. Use of catechins and ornithine for producing a prophylactic or ameliorating agent for hyperammonemia.

18. Use of catechins and ornithine for producing a prophylactic or ameliorating agent for hepatic encephalopathy.

19. Use of catechins and ornithine for producing a prophylactic or ameliorating agent for chronic fatigue syndrome.

20. Use according to any one of claims 9 to 19, wherein:

the catechin is at least 1 selected from catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate.

21. Use according to any one of claims 9 to 20, wherein:

the agent is a pharmaceutical or quasi-pharmaceutical, and contains 0.1 to 20 mass% of the catechins.

22. The use according to claim 21, wherein:

the agent contains 0.3 to 60 mass% of the ornithine.

23. Use according to any one of claims 9 to 20, wherein:

preferably, the agent is a food and contains 0.05 to 10 mass% of the catechins.

24. The use according to claim 23, wherein:

the agent contains 0.15 to 30 mass% of the ornithine.

25. Use according to any one of claims 9 to 24, wherein:

the mass ratio of the catechins to the ornithine in the preparation is 1: 0.1-10.

26. Use according to any one of claims 9 to 25, wherein:

the preparation is oral preparation.

27. Non-therapeutic use of catechins and ornithine for promoting ammonia metabolism.

28. Non-therapeutic use of catechins and ornithine for improving endurance.

29. Non-therapeutic use of catechins and ornithine for combating fatigue.

30. Non-therapeutic use of catechins and ornithine for inhibiting the decrease in blood glucose level due to exercise.

31. Non-therapeutic use of catechins and ornithine for promoting recovery from a decrease in blood glucose level due to exercise.

32. Non-therapeutic use of catechins and ornithine for inhibiting muscle glycogen reduction due to exercise.

33. Non-therapeutic use of catechins and ornithine to promote recovery from muscle glycogen reduction due to exercise.

34. Non-therapeutic use of catechins and ornithine for increasing muscle endurance.

35. The non-therapeutic use according to any one of claims 27 to 34, wherein:

the mass ratio of the catechins to the ornithine is 1: 0.1-10.

36. The non-therapeutic use according to any one of claims 27 to 35, wherein:

the catechins and ornithine are administered orally.

37. A combination of catechins and ornithine for use in the prevention or amelioration of hyperammonemia.

38. A combination of catechins and ornithine for use in the prevention or amelioration of hepatic encephalopathy.

39. A combination of catechins and ornithine for use in the prevention or amelioration of chronic fatigue syndrome.

40. A combination of catechins and ornithine as claimed in any one of claims 37 to 39, wherein:

the mass ratio of the catechins to the ornithine is 1: 0.1-10.

41. A combination of catechins and ornithine as claimed in any one of claims 37 to 40, wherein:

oral administration is carried out.

42. An ammonia metabolism promoting method characterized by:

comprising the step of administering to a subject in need of promotion of ammonia metabolism an effective amount of a catechin and an ornithine.

43. A method for improving endurance, characterized by:

comprising the step of administering an effective amount of catechins and ornithine to a subject in need of improvement of endurance.

44. An anti-fatigue method, characterized by:

comprising the step of administering an effective amount of catechins and ornithine to a subject in need of anti-fatigue.

45. A method for suppressing a decrease in blood glucose level due to exercise, comprising:

comprises administering an effective amount of catechins and ornithine to a subject in need of inhibition of blood glucose level lowering due to exercise.

46. A method for promoting recovery from a decrease in blood glucose level due to exercise, comprising:

comprises administering an effective amount of catechins and ornithine to a subject in need of promotion of recovery from a decrease in blood glucose level due to exercise.

47. A method of inhibiting muscle glycogen reduction caused by exercise, comprising:

comprising the step of administering an effective amount of catechins and ornithine to a subject in need of inhibition of muscle glycogen reduction due to exercise.

48. A method of promoting recovery from muscle glycogen reduction due to exercise, characterized by:

comprising the step of administering an effective amount of catechins and ornithine to a subject in need of promotion of recovery from muscle glycogen reduction due to exercise.

49. A method for improving muscle endurance, comprising:

comprising the step of administering to a subject in need of an increase in muscle endurance an effective amount of a catechin and an ornithine.

50. A method for preventing or ameliorating hyperammonemia, comprising:

comprising the step of administering catechins and ornithine in an effective amount to a subject in need of prevention or amelioration of hyperammonemia.

51. A method for preventing or ameliorating hepatic encephalopathy, comprising:

comprising the step of administering catechins and ornithine in an effective amount to a subject in need of prevention or amelioration of hepatic encephalopathy.

52. A method for preventing or ameliorating chronic fatigue syndrome, comprising:

comprising the step of administering catechins and ornithine in an effective amount to a subject in need of prevention or amelioration of chronic fatigue syndrome.

53. The method of any one of claims 42 to 52, wherein:

the mass ratio of the catechins to the ornithine is 1: 0.1-10.

54. A method according to any one of claims 42 to 53, wherein:

preferably, the administration is oral.

Technical Field

The invention relates to a raw material for promoting ammonia metabolism in vivo, exerting endurance improving effect and anti-fatigue effect.

Background

In vivo, amino acids are mainly produced in the process of catabolism of amino acids, such as decomposition of muscles by protein metabolism or exercise. Ammonia suppresses the oxidation of pyruvate to acetyl CoA, which causes fatigue (see non-patent document 1). Further, it is known that ammonia causes a decrease in the function of the nervous system and causes central fatigue, promotes accumulation of lactic acid in muscles and promotes muscle fatigue (patent document 1), and that hyperammonemia causes various disorders such as brain disorders (non-patent document 2). Accumulation of ammonia in patients with chronic liver diseases is considered to play an important role in the development of hepatic encephalopathy and multi-organ failure (respiratory failure, cardiovascular failure, renal failure) (patent document 2).

The ammonia in the body is converted into nontoxic urea through the urea circulation of the liver and is discharged into urine. Arginine, ornithine and citrulline are involved in the urea cycle of the liver which converts ammonia to non-toxic urea. It has been reported that the increase of blood ammonia is suppressed by ornithine, citrulline, or arginine, which are amino acids involved in the urea cycle (patent documents 3 and 4 and non-patent document 1). In the organism, citrulline is synthesized from ornithine and is converted into arginine. There is a report of using ornithine to suppress the increase in blood ammonia and improve fatigue (see patent document 3). Further, it has been reported that arginine in blood is increased by citrulline intake, or brain fatigue is improved (patent documents 4 and 5).

The endurance is necessary not only in sports competition but also in simple movements such as walking and running or in labor for repeatedly performing muscle work in our daily life. The decrease in endurance is a cause of difficulty in daily activities particularly for the elderly, and has a great adverse effect on quality of life (QOL). In terms of improvement of endurance, exercise training is widely considered to be effective, but since it is difficult to maintain time or motivation and there is a fear of injury to elderly persons, it is not easy at all to maintain or improve endurance through training.

Catechins have been reported as components having an effect of preventing an increase in endurance or fatigue (patent documents 6 and 7). However, there is no report on the action of catechins on ammonia metabolism.

As other components having an effect of improving endurance or preventing fatigue, various amino acids, for example, ornithine (patent document 3), citrulline (non-patent document 1), a combination of citrulline and arginine (patent document 4), arginine, a combination of ornithine and citrulline (non-patent document 3), and the like have been reported.

Patent document 1: japanese laid-open patent publication No. 2000-239179

Patent document 2: japanese patent laid-open publication No. 2012-246294

Patent document 3: japanese patent laid-open publication No. 2011-132174

Patent document 4: international laid-open publication No. 2009/048148

Patent document 5: japanese patent laid-open publication No. 2013-060406

Patent document 6: japanese laid-open patent publication No. 2005-089384

Patent document 7: japanese patent laid-open No. 2008-031148

Non-patent document 1: takeda et al, J Nutr Sci Vitaminol,2011,57:246-

Non-patent document 2: walker, Diabetes, Obesity and Metabolism,2009,11:823-

Non-patent document 3: meneguello et al, Cell Biochem Funct,2003,21:85-91

Disclosure of Invention

The invention provides an ammonia metabolism promoter which takes catechins and ornithine as effective components.

The present invention also provides an agent for improving endurance, which comprises catechins and ornithine as active ingredients.

The present invention also provides an anti-fatigue agent containing catechins and ornithine as active ingredients.

Further, the present invention provides an inhibitor for the decrease in blood glucose level due to exercise, which contains catechins and ornithine as active ingredients.

The present invention also provides a promoter for recovery from a decrease in blood glucose level due to exercise, which comprises catechins and ornithine as active ingredients.

The present invention also provides an agent for inhibiting muscle glycogen reduction caused by exercise, which comprises catechins and ornithine as active ingredients.

Further, the present invention provides a muscle-endurance improver comprising catechins and ornithine as active ingredients.

Further, the present invention provides a food for promoting ammonia metabolism, which contains catechins and ornithine as active ingredients.

Further, the present invention provides a food for improving endurance, which contains catechins and ornithine as active ingredients.

The present invention also provides an anti-fatigue food containing catechins and ornithine as active ingredients.

Further, the present invention provides a food for suppressing a decrease in blood glucose level due to exercise, which contains catechins and ornithine as active ingredients.

The present invention also provides a food for promoting recovery from a decrease in blood glucose level due to exercise, which contains catechins and ornithine as active ingredients.

The present invention also provides a food for inhibiting muscle glycogen reduction caused by exercise, which contains catechins and ornithine as active ingredients.

Further, the present invention provides a food for improving muscle endurance, which contains catechins and ornithine as active ingredients.

Drawings

Fig. 1 shows the effect of catechins and ornithine on ammonia metabolism of hepatocytes, the horizontal axis represents the medium in which hepatocytes were cultured, and the vertical axis represents the ammonia concentration in the medium, and the data are mean values ± SE (n ═ 3), ＊ p < 0.05 (dunnettest, relative to the control group).

FIG. 2 shows the effect of catechins and ornithine on blood ammonia concentration during exercise. A: post exercise blood ammonia concentration for 1 st (no intake of test material), B: post-exercise blood ammonia concentration at 2 nd (after intake of test material), C: delta blood ammonia concentration (measured at exercise 2-1 st). Data are mean ± SE (each group n is 9).

Fig. 3 shows auc data for Δ blood ammonia concentrations as mean ± SE (n-9 in each group), ＊ p < 0.05(t-test, relative to group (i)).

Fig. 4 is the result of the fatigue questionnaire.

FIG. 5 shows the results of the measurement of delta blood ammonia concentration (A) and delta glucose concentration (B) in the muscle endurance test at rest, before the 1 st continuous myodynamia measurement, after the 1 st continuous myodynamia measurement, immediately after the 1 st continuous myodynamia measurement, after the 2 nd continuous myodynamia measurement, immediately after the 2 nd continuous myodynamia measurement, after the 10 th continuous myodynamia measurement, after the 2 nd continuous myodynamia measurement, after the 20 th continuous myodynamia measurement, after the 2 nd continuous myodynamia measurement, after the control group, Cat + Orn, catechins and ornithine in combination, and the data are the average of the measurement values in the 2 tests formed in the cross test. + -. SE (each group.

Fig. 6 shows applied muscle force measured in the muscle endurance test Cont: control group, Cat + Orn: catechins and ornithine were used in combination, and the data is the average of applied muscle force ± SE (n: 18 for each group) ＊ p < 0.05(ANOVA) of both feet of all the subjects measured in 2 tests.

Figure 7 is the mouse treadmill (Treadmoll) limit travel time data mean + -SE (n 7 ~ 8), ＊ p < 0.05(Dunnett, relative to control).

Data are mean ± SE (n ═ 7-8), ＊ p < 0.05(Tukey post hoc one way anova, one-way anova post hoc Tukey test).

Detailed Description

All patent documents, non-patent documents, and other publications cited in this specification are incorporated herein by reference in their entirety.

In the present specification, "non-therapeutic" is a concept that does not include medical practice, that is, a method of performing surgery, treatment, or diagnosis on a human body, and more specifically, a concept that does not include a method of performing surgery, treatment, or diagnosis on a human body by a doctor, a medical practitioner, or a person who receives an instruction from a doctor.

In the present specification, "prevention" refers to prevention, inhibition, or delay of onset of a disease or symptom in an individual, or reduction of risk of onset of a disease or symptom in an individual. In the present specification, "improvement" means improvement of a disease or symptom, prevention, inhibition, or delay of worsening of a disease or symptom, or reversal, prevention, inhibition, or delay of progression of a disease or symptom.

In the present specification, "exercise" refers to, for example, sports competitions (narrow sense exercises) such as sports, training, and aerobic exercises, and also refers to general physical exercises including labor accompanied by muscle work and daily movements. In the present specification, "exercise" may mean a situation in which an athlete or a person who performs a narrow sense of exercise, preferably a narrow sense of exercise, and "exercise" may mean a situation in which the athlete is a middle-aged or elderly person, a weak person, a patient, a person in a recovery period from a disease, labor with muscle work, or daily activities.

In the present specification, "endurance" refers to endurance against the above-mentioned "sport," and "endurance improvement" is a concept including improvement of endurance and suppression of reduction of endurance. In the present specification, "fatigue resistance" means suppression of fatigue caused by the "exercise" or promotion of recovery thereof.

In the present specification, "muscle endurance" refers to endurance of skeletal muscle, that is, ability of skeletal muscle to continuously exert muscle strength, and "improvement of muscle endurance" refers to inhibition of decrease in muscle strength of skeletal muscle in a state of continuous driving. The term "improvement in muscular endurance" also includes a state in which the reduction in full-force exercise ability is suppressed at the repetition of intermittent short-time full-force exercise (jerking, jumping, sprinting, or the like).

In the present specification, the phrase "a decrease in blood glucose level due to exercise" refers to a decrease in blood glucose level due to an increase in sugar consumption due to exercise, which occurs during exercise, immediately after an interruption in exercise, or immediately after the end of exercise. In the present specification, the phrase "recovery from a decrease in blood glucose level due to exercise" refers to recovery from a blood glucose level occurring after an interruption in exercise or after completion of exercise in a state where blood glucose is decreased due to an increase in sugar consumption due to exercise.

In the present specification, "reduction in muscle glycogen by exercise" refers to reduction in glycogen storage in muscle due to consumption of muscle glycogen by muscle contraction activity. In the present specification, the term "recovery from a decrease in muscle glycogen due to exercise" refers to recovery from a decrease in muscle glycogen due to exercise after an interruption in exercise or after the end of exercise.

In the present specification, "catechin" means at least 1 selected from the group consisting of catechin (C), Gallocatechin (GC), catechin gallate (Cg), gallocatechin gallate (GCg), Epicatechin (EC), Epigallocatechin (EGC), epicatechin gallate (ECg), and epigallocatechin gallate (EGCg).

Catechins can be extracted from tea leaves produced from leaves of the genus Camellia (Camellia), such as C.sinensis var. sinensis, C.sinensisvar. assamica, Obelia species, or these hybrids, with water or hot water, optionally with the addition of an extraction aid thereto. The tea comprises: (1) tea leaves of green tea such as decocted tea, sencha, yulu, ground tea, and kettle-fried tea; (2) half-fermented tea such as TIEGUANYIN, TINGYANG, HUANGJINGUI, WUYIYAN tea, etc. collectively called oolong tea; (3) tea leaves of fermented tea such as Dajiling tea, Wuba tea, Qimen tea, etc., which are called black tea. The extraction of catechins from the tea leaves can be carried out by a usual method such as agitation extraction. Organic acid or organic acid salt such as sodium ascorbate may be added in advance to the water or hot water for extraction. If necessary, extraction may be carried out in a so-called non-oxidizing atmosphere while removing dissolved oxygen by boiling and degassing or introducing an inert gas such as nitrogen gas during extraction.

Alternatively, instead of directly extracting catechins from tea leaves, a concentrate or a purified product of a tea extract may be used as the catechins. The concentrate of the tea extract refers to, for example, a product obtained by concentrating an extract obtained by extracting tea leaves with hot water or a water-soluble organic solvent, and the purified product of the tea extract refers to, for example, a product obtained by purifying the extract using a solvent, a column, or the like. Examples of the concentrate or purified product of the tea extract include those obtained by the methods described in detail in Japanese patent application laid-open No. 59-219384, Japanese patent application laid-open No. 4-20589, Japanese patent application laid-open No. 5-260907, Japanese patent application laid-open No. 5-306279, and the like. The tea extract and its concentrate or refined product can be commercially available products, and examples thereof include "polyphenone" of sanjing agriculture and forestry, TEAFLAN of ita, SUN chemists, SUN ooling, and the like. The form of the concentrate or the purified product of the tea extract is not particularly limited, and examples thereof include a solid, a liquid, a slurry, and a tea extract obtained by dissolving or diluting these in water, carbonated water, or a usual procedure.

The catechins in the present invention may be derived from other sources than tea leaves, for example, from grapes and processed products thereof (wine, fruit juices, etc.), cocoa beans and processed products thereof, or chemically synthesized products.

The catechins of the present invention are preferably used in the form of a concentrate or a purified product of a tea extract, and more preferably in the form of a concentrate or a purified product of a green tea extract.

In the present invention, ornithine may be used in the form of an episome or a salt thereof. Ornithine may be any of L-, D-, DL-and mixtures thereof, preferably L-form.

Examples of the salts of ornithine include acid addition salts, metal salts, ammonium salts, organic amine addition salts, and amino acid addition salts. Examples of the acid addition salt include inorganic acid salts such as hydrochloride, sulfate, nitrate and phosphate, and organic acid salts such as acetate, maleate, fumarate, citrate, malate, lactate, α -ketoglutarate, gluconate and caprylate. Examples of the metal salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt, and zinc salt. Examples of the ammonium salt include ammonium salts, tetramethylammonium salts, and the like. Examples of the organic amine addition salt include salts such as morpholine and piperidine. Examples of the amino acid addition salt include salts of glycine, phenylalanine, lysine, aspartic acid, glutamic acid, and the like. Among them, sodium salt or hydrochloride salt is cited as a preferable example.

The free form of ornithine or the salts thereof can be obtained by a method of isolation and purification from animals and plants containing the same, chemical synthesis, fermentation production, or the like. Or may be purchased commercially.

The present invention relates to a raw material having an excellent ammonia metabolism promoting effect, an improved endurance, an improved muscle endurance, an inhibition of a decrease in muscle glycogen or a decrease in blood glucose level due to exercise, a promotion of recovery from a decrease in muscle glycogen or a decrease in blood glucose level due to exercise, and an anti-fatigue effect.

The present inventors have found that by using a combination of catechins and ornithine, ammonia metabolism in hepatocytes is significantly improved as compared with the case of using catechins alone or ornithine alone. Furthermore, the inventors of the present invention have found that, in individuals who ingest catechins and ornithine in combination, an increase in blood ammonia concentration during exercise and a decrease in blood glucose level and muscle glycogen are suppressed, and recovery of blood glucose level decreased by exercise is promoted, and further, an improvement in endurance, an improvement in muscle endurance, and an anti-fatigue effect can be obtained.

The present invention promotes ammonia metabolism in vivo, prevents decrease in muscle glycogen or decrease in blood glucose level due to exercise, and reduces fatigue, improves endurance, or improves muscle endurance. According to the present invention, it is possible to improve endurance of sports such as a weak person, a middle-aged or elderly person, or a person (for example, an athlete) who has a need to improve a sports function, who is afflicted with reduction in endurance or fatigue, or to reduce fatigue due to sports.

In the present invention, by using both catechin and ornithine, a remarkably high ammonia metabolism promoting effect and endurance improving or anti-fatigue effect are achieved as compared with the case where catechin or ornithine is used alone. In the present invention, by using a combination of catechins and ornithine, an inhibitory effect on reduction of muscle glycogen or reduction of blood glucose level due to exercise, or a promoting effect on recovery of muscle glycogen or blood glucose level due to exercise can be obtained. In the present invention, by using a combination of catechins and ornithine, a muscle endurance-improving effect can be obtained. In the present invention, the catechins and ornithine may be administered simultaneously as 1 composition containing both components or may be administered separately as long as these substances can act synergistically in the living body.

Accordingly, in one embodiment, the present invention provides an ammonia metabolism promoter comprising catechins and ornithine as active ingredients. The present invention also provides an agent for improving endurance comprising catechins and ornithine as active ingredients. The present invention also provides an anti-fatigue agent containing catechins and ornithine as active ingredients. The present invention also provides an inhibitor for the decrease in blood glucose level due to exercise, which contains catechins and ornithine as active ingredients. The present invention also provides a promoter for recovery from a decrease in blood glucose level due to exercise, which comprises catechins and ornithine as active ingredients. Further, the present invention provides a muscle endurance improver comprising catechins and ornithine as active ingredients. The present invention also provides an inhibitor for reducing muscle glycogen caused by exercise, which contains catechins and ornithine as active ingredients. The present invention also provides a promoter for recovery from muscle glycogen reduction caused by exercise, which comprises catechins and ornithine as active ingredients.

In another aspect, the present invention provides use of a catechin and ornithine for producing an accelerator for ammonia metabolism, an agent for improving endurance, an anti-fatigue agent, an inhibitor of a decrease in blood glucose level due to exercise, an accelerator for recovery from a decrease in blood glucose level due to exercise, an inhibitor of a decrease in muscle glycogen due to exercise, an accelerator for recovery from a decrease in muscle glycogen due to exercise, or an agent for improving muscle endurance.

In one embodiment, the ammonia metabolism-promoting agent, endurance-improving agent, anti-fatigue agent, inhibitor of decrease in blood glucose level due to exercise, promoter of recovery from decrease in blood glucose level due to exercise, inhibitor of decrease in muscle glycogen due to exercise, promoter of recovery from decrease in muscle glycogen due to exercise, and muscle endurance-improving agent of the present invention are compositions containing at least catechins and ornithine. In another embodiment, the agent of the invention may consist essentially of catechins and ornithine.

In another aspect, the present invention provides use of a catechin and ornithine for promoting ammonia metabolism, improving endurance, resisting fatigue, suppressing a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, suppressing a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise, or improving muscle endurance. In a preferred embodiment, the catechins and ornithine are used in the form of a composition containing these substances.

In another aspect, the present invention provides a combination of catechins and ornithine for use in promoting ammonia metabolism, improving endurance, resisting fatigue, suppressing a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, suppressing a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise, or improving muscle endurance. In a preferred embodiment, the combination of catechins and ornithine is a composition containing these substances.

Examples of the composition containing catechins and ornithine include a pharmaceutical product, a quasi-pharmaceutical product, a food, and the like, which will be described later.

The uses of the catechins and ornithine of the present invention may include therapeutic uses and non-therapeutic uses. As the use of the non-therapeutic treatment, for example, catechins and ornithine are administered or ingested as non-medical acts for the purpose of obtaining health-promoting effects such as reduction of fatigue due to physical activities in daily life, improvement of durability or fatigue reduction in labor accompanied by muscle work, improvement of endurance in narrow sense of exercise, and promotion of recovery from fatigue during or after narrow sense of exercise. For example, as a non-therapeutic use, there is a case where catechins and ornithine are provided for the purpose of administering them to other people as a non-medical act or allowing them to take them, and the health-promoting effect is claimed.

The therapeutic use is applicable to prevention or improvement of diseases or symptoms caused by excessive accumulation of ammonia, such as chronic fatigue syndrome, hyperammonemia, hepatic encephalopathy, and the like.

In the present invention, catechins and ornithine can be used for both human and non-human animals. Examples of the non-human animal include a non-human mammal, an amphibian, and cartilaginous fishes, and examples of the non-human mammal include a simian, another primate, a mouse, a rat, a horse, a cow, a pig, a sheep, a dog, a cat, a hamster, and a companion animal.

In addition, in other embodiments, the present invention provides a method for promoting ammonia metabolism in a subject. In addition, the present invention provides a method for improving endurance of an object. Additionally, the present invention provides a method of combating fatigue in a subject. Further, the present invention provides a method for suppressing a decrease in blood glucose level due to exercise in a subject. Further, the present invention provides a method for promoting recovery from a decrease in blood glucose level due to exercise in a subject. In addition, the present invention provides a method for inhibiting a decrease in muscle glycogen caused by exercise in a subject. In addition, the present invention provides a method of promoting recovery from muscle glycogen reduction caused by exercise in a subject. In addition, the present invention provides a method of improving muscle endurance in a subject. The present invention also provides a method for preventing or ameliorating a disease or a symptom caused by excessive accumulation of ammonia in a subject. The method comprises the step of administering an effective amount of a catechin and an ornithine to the subject. In a preferred embodiment, a composition comprising catechins and ornithine is administered. In other preferred embodiments, administration is oral.

Examples of subjects to which the method of the present invention is applied include the human and non-human animals that require promotion of ammonia metabolism, improvement of endurance, fatigue resistance, suppression of decrease in blood glucose level due to exercise, promotion of recovery from decrease in blood glucose level due to exercise, suppression of decrease in muscle glycogen due to exercise, promotion of recovery from decrease in muscle glycogen due to exercise, or improvement of muscle endurance, and the human and non-human animals that require prevention or improvement of diseases or symptoms caused by excessive accumulation of ammonia such as chronic fatigue syndrome, hyperammonemia, hepatic encephalopathy.

Further examples of the subject include the human and non-human animals that require reduction of fatigue due to physical activity in daily life, improvement of endurance or reduction of fatigue in labor accompanied by muscle work, improvement of endurance or muscle endurance in a narrow sense of exercise, promotion of recovery from fatigue in or after the narrow sense of exercise, and the like.

Further examples of subjects include subjects in which prevention or improvement of symptoms caused by hyperammonemia is required, such as Respiratory alkalosis (Respiratory alkalosis), Slurred mouth (Respiratory speed), Tremors (Tremors), Weakness (Weakness), increase or decrease in muscle tone (acquired or acquired muscle tone), dyskinesia (Ataxia), Hypothermia (hyperthermia), Seizure (Seizure), cerebral edema (Brain edema), Coma (Coma), cerebral stress (Brain stress), confusion with headache (headache), nausea (Nausea), Vomiting (Vomiting), hyperactivity (activity), Delusions and hallucinations (delusion and delrium), allergy (irritability), Aggression (activity), hyperactivity, bizarre-or self-disabling behavior (Hyperactive, bizarre or self-immobility behavior), cognitive impairment (cognitive deficiencies), Protein aversion (Protein aversion), Anorexia (Anorexia), growth retardation (Delayedgrowth), and the like. .

Further examples of the subject include the human and non-human animals described above, which require suppression of central fatigue associated with a decrease in the function of the nervous system due to accumulation of ammonia, and suppression of drowsiness or feelings of drowsiness due to the central fatigue.

Further examples of the subject include the above-mentioned human and non-human animals in need of prevention or improvement of symptoms or conditions accompanied by an increase in blood ammonia concentration, such as aphasia, weakness, coma, disturbance of consciousness, blurred vision, developmental disorder, protein-induced emesis, and a decrease in lactation ability in infants and young children.

Alternatively, the ammonia metabolism promoting method of the present invention may be an in vitro method, and examples of the target to which the in vitro method is applied include liver tissues and cultured hepatocytes (for example, primary liver cultured cells) derived from the above-mentioned human or non-human animals.

The effective amount to be administered in the method of the present invention may be an amount capable of promoting ammonia metabolism in a subject, an amount capable of improving endurance or resisting fatigue in a subject, an amount capable of suppressing decrease in muscle glycogen or decrease in blood glucose level due to exercise in a subject, or an amount capable of promoting recovery from decrease in muscle glycogen or decrease in blood glucose level due to exercise, or an amount capable of improving muscle endurance in a subject. The ammonia metabolism level can be evaluated by measuring the blood ammonia concentration of the subject, the urea production amount, the ammonia concentration of the medium in which the hepatocytes are cultured, and the like. Endurance or fatigue resistance can be evaluated by a treadmill (pedal) test, a bicycle pedal test, or other exercise tests. The blood glucose level can be evaluated by a general blood glucose level measuring instrument. The amount of glycogen in muscle can be evaluated by collecting skeletal muscle, extracting glycogen, and quantifying glycogen using a special kit or the like. Muscle endurance can be evaluated by successive muscle strength measurement tests. In one embodiment, the effective amount may be an amount that causes a statistically significant increase in the ammonia metabolism level of the group to which catechins and ornithine are administered, as compared with the group to which no drug is administered. In another embodiment, the effective amount may be an amount that causes a statistically significant decrease in blood ammonia concentration in a group of individuals to whom catechins and ornithine are administered, as compared with a group to which no catechin is administered. In another embodiment, the effective amount may be an amount that statistically significantly increases the blood glucose level during or after exercise in the group of individuals to which catechins and ornithine are administered, as compared with the group without the administration of the drug. In yet another embodiment, the effective amount may be an amount that statistically significantly prolongs the exercise time of the group of individuals administered catechins and ornithine compared to the group not administered. In still another embodiment, the effective amount may be an amount such that a decrease in muscle strength associated with exercise in a group of subjects to which catechins and ornithine are administered is statistically significantly inhibited as compared to the group without the administration.

In the present invention, catechins and ornithine are useful as active ingredients for imparting functions of promoting ammonia metabolism, improving endurance, resisting fatigue, suppressing a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, suppressing a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise, or improving muscle endurance to pharmaceuticals, quasi-pharmaceuticals, foods (including foods for non-human animals), and the like, or as active ingredients for preventing or improving diseases or symptoms caused by excessive accumulation of ammonia such as chronic fatigue syndrome, hyperammonemia, hepatic encephalopathy, and the like.

The pharmaceutical product (including quasi-pharmaceutical products) is a pharmaceutical product for promoting ammonia metabolism, improving endurance, relieving fatigue, suppressing a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, suppressing a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise, or improving muscle endurance, or preventing or ameliorating diseases or symptoms caused by excessive accumulation of ammonia such as chronic fatigue syndrome, hyperammonemia, hepatic encephalopathy, and the like, and catechins and ornithine are contained as active ingredients for the functions. The pharmaceutical product may contain a pharmaceutically acceptable carrier, other active ingredients, pharmacological ingredients, and the like as needed to such an extent that the function of the active ingredients is not lost. The pharmaceutical product can be provided as 1 composition containing catechin and ornithine, or as a combination of multiple compositions containing catechin or ornithine.

The pharmaceutical (including quasi-pharmaceutical) may be administered orally or parenterally, and preferably orally. The dosage form of the pharmaceutical is not particularly limited as long as it can be administered orally or non-orally, and may be any of, for example, injections, suppositories, inhalants, transdermal absorbents, various external preparations, tablets, capsules, granules, powders, liquids, syrups and the like, and preparations of such various dosage forms can be prepared by a conventional method by appropriately combining catechins and ornithine with pharmaceutically acceptable carriers (for example, excipients, binders, extenders, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, perfumes, coating agents, diluents and the like), other pharmaceutical ingredients, and the like.

The food is a food for providing a function of promoting ammonia metabolism, improving endurance, relieving fatigue, suppressing a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, suppressing a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise, or improving muscle endurance, and contains catechins and ornithine as active ingredients for the function. The food includes health functional foods such as a patient food, a nutritional functional food, a specific health food, and a functional food or drink showing the effect as necessary, which promote ammonia metabolism, improve endurance, resist fatigue, suppress a decrease in blood glucose level due to exercise, promote recovery from a decrease in blood glucose level due to exercise, suppress a decrease in muscle glycogen due to exercise, promote recovery from a decrease in muscle glycogen due to exercise, or improve muscle endurance, and a plant concept.

Food products provided according to the invention include beverages. Therefore, the food may be referred to as a food or drink. The food product may be in the form of a solid, semi-solid or liquid (e.g. a beverage). Examples of the food include snacks such as bread, noodles, rice and cookies, jellies, dairy products, soups, frozen foods, instant foods, processed starch products, processed fish products, other processed foods, seasonings, nutritional supplements, beverages such as tea or coffee beverages, fruit beverages, carbonated beverages, and jelly-like beverages, and raw materials thereof. Alternatively, the food product may be a supplement in the form of an orally administered preparation such as a tablet, capsule, granule, powder, liquid, syrup, etc. The food can be provided as 1 composition containing catechin and ornithine, or as a combination of multiple compositions containing catechin or ornithine.

The food can be prepared by combining catechins and ornithine as appropriate with any food material or any additive acceptable in food (for example, solvent, softener, oil, emulsifier, preservative, perfume, sweetener, stabilizer, colorant, ultraviolet absorber, antioxidant, humectant, thickener, fixing agent, dispersant, humectant, etc.) according to a conventional method.

The content of catechins in the pharmaceutical product (including quasi-pharmaceutical products) is not particularly limited, but is preferably 0.1% by mass or more, more preferably 1% by mass or more, and still more preferably 3% by mass or more, and is preferably 20% by mass or less, more preferably 10% by mass or less, and still more preferably 5% by mass or less. Further, examples of the content include 0.1 to 20% by mass, 0.1 to 10% by mass, 0.1 to 5% by mass, 1 to 20% by mass, 1 to 10% by mass, 1 to 5% by mass, 3 to 20% by mass, 3 to 10% by mass, and 3 to 5% by mass.

The content of ornithine in the drug (including quasi-drug) is not particularly limited, but is preferably 0.3% by mass or more, more preferably 3% by mass or more, further preferably 5% by mass or more, further preferably 9% by mass or more, and preferably 60% by mass or less, more preferably 30% by mass or less, further preferably 20% by mass or less, further preferably 15% by mass or less in terms of ornithine free body. Further, examples of the content include 0.3 to 60% by mass, 0.3 to 30% by mass, 0.3 to 20% by mass, 0.3 to 15% by mass, 3 to 60% by mass, 3 to 30% by mass, 3 to 20% by mass, 3 to 15% by mass, 5 to 60% by mass, 5 to 30% by mass, 5 to 20% by mass, 5 to 15% by mass, 9 to 60% by mass, 9 to 30% by mass, 9 to 20% by mass, and 9 to 15% by mass.

In the pharmaceutical product (including quasi-pharmaceutical products), any one of the above-mentioned concentrations (0.1 to 20 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 1 to 20 mass%, 1 to 10 mass%, 1 to 5 mass%, 3 to 20 mass%, 3 to 10 mass%, and 3 to 5 mass%) of the catechins can be arbitrarily combined with any one of the above-mentioned concentrations (0.3 to 60 mass%, 0.3 to 30 mass%, 0.3 to 20 mass%, 0.3 to 15 mass%, 3 to 60 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 5 to 60 mass%, 5 to 30 mass%, 5 to 20 mass%, 5 to 15 mass%, 9 to 60 mass%, 9 to 30 mass%, and 9 to 15 mass%) of ornithine.

The content of catechins in the food is not particularly limited, but is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, further preferably 1% by mass or more, and preferably 10% by mass or less, more preferably 5% by mass or less, further preferably 1% by mass or less. Further, examples of the content include 0.05 to 10% by mass, 0.05 to 5% by mass, 0.05 to 1% by mass, 0.1 to 10% by mass, 0.1 to 5% by mass, 0.1 to 1% by mass, 1 to 10% by mass, and 1 to 5% by mass.

The content of ornithine in the food is not particularly limited, but is preferably 0.15% by mass or more, more preferably 0.3% by mass or more, further preferably 3% by mass or more, further preferably 5% by mass or more, and preferably 30% by mass or less, more preferably 20% by mass or less, further preferably 15% by mass or less, further preferably 5% by mass or less, and further preferably 3% by mass or less in terms of ornithine free body. Further, examples of the content include 0.15 to 30% by mass, 0.15 to 20% by mass, 0.15 to 15% by mass, 0.15 to 5% by mass, 0.15 to 3% by mass, 0.3 to 30% by mass, 0.3 to 20% by mass, 0.3 to 15% by mass, 0.3 to 5% by mass, 0.3 to 3% by mass, 3 to 30% by mass, 3 to 20% by mass, 3 to 15% by mass, 3 to 5% by mass, 5 to 30% by mass, 5 to 20% by mass, and 5 to 15% by mass.

In the food, any one of the above-mentioned concentrations (0.05 to 10 mass%, 0.05 to 5 mass%, 0.05 to 1 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 0.1 to 1 mass%, 1 to 10 mass%, and 1 to 5 mass%) of the catechins can be arbitrarily combined with any one of the above-mentioned concentrations (0.15 to 30 mass%, 0.15 to 20 mass%, 0.15 to 15 mass%, 0.15 to 5 mass%, 0.15 to 3 mass%, 0.3 to 20 mass%, 0.3 to 30 mass%, 0.3 to 15 mass%, 0.3 to 5 mass%, 0.3 to 3 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 3 to 5 mass%, 5 to 30 mass%, 5 to 20 mass%, and 5 to 15 mass%) of ornithine.

In the present invention, the amounts and administration schedules of catechins and ornithine may be appropriately determined by those skilled in the art according to the kind, body weight, sex, age, condition of the subject, or other factors. In the case of oral administration, examples of the dose of catechins and ornithine of the present invention administered to 1 adult per 1 day are as follows:

[ catechins ] are preferably 100 to 3000mg/60kg body weight, more preferably 250 to 2000mg/60kg body weight, still more preferably 250 to 1000mg/60kg body weight, and yet more preferably 250 to 600mg/60kg body weight;

[ ornithine (in terms of free body) ] is preferably 100 to 5000mg/60kg of body weight, more preferably 250 to 3000mg/60kg of body weight, even more preferably 400 to 2000mg/60kg of body weight, even more preferably 500 to 2000mg/60kg of body weight, even more preferably 800 to 1600mg/60kg of body weight, and in other examples, is preferably 250 to 800mg/60kg of body weight, even more preferably 500 to 800mg/60kg of body weight;

the above-mentioned amount is preferably administered, for example, 1 time per day, or 2 or 3 times per day.

The mass ratio of catechins to ornithine (in terms of free body) used in the present invention is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, even more preferably 1: 1 to 8, even more preferably 1: 1 to 5, and even more preferably 1: 2 to 4. For example, the content ratio of catechins to ornithine in the accelerator for ammonia metabolism, the endurance improver, the anti-fatigue agent, the inhibitor of decrease in blood glucose level due to exercise, the accelerator of recovery from decrease in blood glucose level due to exercise, the inhibitor of decrease in muscle glycogen due to exercise, the accelerator of recovery from decrease in muscle glycogen due to exercise, the enhancer of muscle endurance improver, and the agent for preventing or ameliorating a disease or a symptom caused by excessive accumulation of ammonia according to the present invention is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, further preferably 1: 1 to 8, further preferably 1: 1 to 5, and further preferably 1: 2 to 4 in terms of a mass ratio. For example, the ratio of the amount of catechins to ornithine to be administered in the method for promoting ammonia metabolism, improving endurance, resisting fatigue, inhibiting a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, inhibiting a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise or improving muscle endurance of the present invention, and the method for preventing or ameliorating a disease or condition caused by excessive accumulation of ammonia is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, further preferably 1: 1 to 8, further preferably 1: 1 to 5, and further preferably 1: 2 to 4 in terms of mass ratio.

In a preferred embodiment of the non-therapeutic use of catechins and ornithine of the present invention for promoting ammonia metabolism, improving endurance, resisting fatigue, inhibiting a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, inhibiting a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise, or improving muscle endurance, the catechins and ornithine are provided as a composition containing 1 to 10% by mass of catechins and 5 to 20% by mass of ornithine (in terms of free body), and having a mass ratio of catechins to ornithine (in terms of free body) of 1: 0.5 to 10. Preferably the composition is a food product.

In a preferred embodiment of the non-therapeutic use of catechins and ornithine of the present invention for promoting ammonia metabolism, improving endurance, resisting fatigue, inhibiting a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, inhibiting a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise, or improving muscle endurance, the catechins and ornithine are provided as a beverage composition containing 0.057 to 0.567 mass% of catechins and 0.283 to 1.132 mass% (in terms of free bodies) of ornithine, and having a mass ratio of catechins to ornithine (in terms of free bodies) of 1: 0.5 to 10.

In a preferred embodiment of the use of catechins and ornithine of the present invention for promoting ammonia metabolism, improving endurance, resisting fatigue, inhibiting a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, inhibiting a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise or improving muscle endurance, or for the prevention or improvement of chronic fatigue syndrome, hyperammonemia, or hepatic encephalopathy, the catechins and ornithine are provided as a composition containing 1 to 10% by mass of catechins and 5 to 20% by mass of ornithine (in terms of free body), and having a mass ratio of catechins to ornithine (in terms of free body) of 1: 0.5 to 10. Preferably, the composition is a pharmaceutical.

In the present invention, preferred examples of the administration amounts of catechins and ornithine for promoting ammonia metabolism, improving endurance, relieving fatigue, suppressing a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, suppressing a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise or improving muscle endurance, or preventing or improving chronic fatigue syndrome, hyperammonemia, or hepatic encephalopathy are: the amount of catechins administered orally per 1 day for 1 adult is 250 to 1,000mg/60kg body weight and 400 to 2000mg (in terms of free body) of ornithine/60 kg body weight. The above-mentioned amount is preferably administered, for example, 1 time per day, or 2 or 3 times per day.

In the present invention, other materials having effects of promoting ammonia metabolism, improving endurance, relieving fatigue, suppressing a decrease in blood glucose level due to exercise, promoting recovery from a decrease in blood glucose level due to exercise, suppressing a decrease in muscle glycogen due to exercise, promoting recovery from a decrease in muscle glycogen due to exercise, or improving muscle endurance can be used as active ingredients in combination with catechins and ornithine. Examples of such other raw materials include arginine, citrulline, and a combination thereof.

Further illustrative embodiments of the invention include the following materials, methods of manufacture, uses, methods, and the like. However, the present invention is not limited to these embodiments.

[1] An ammonia metabolism promoter contains catechin and ornithine as effective components.

[2] A endurance improver contains catechin and ornithine as effective components.

[3] An antifatigue agent contains catechin and ornithine as effective components.

[4] An inhibitor for blood glucose level decrease due to exercise contains catechin and ornithine as effective components.

[5] A promoter for recovering from blood glucose level decrease due to exercise contains catechin and ornithine as effective components.

[6] An inhibitor for reducing muscle glycogen caused by exercise contains catechin and ornithine as effective components.

[7] A promoter for recovering from muscle glycogen reduction caused by exercise contains catechin and ornithine as effective components.

[8] A muscle endurance improver contains catechin and ornithine as effective components.

[9] A preventing or improving agent for hyperammonemia contains catechin and ornithine as effective components.

[10] A preventive or ameliorating agent for hepatic encephalopathy contains catechin and ornithine as effective components.

[11] A preventive or ameliorating agent for chronic fatigue syndrome contains catechin and ornithine as effective components.

[12] The agent according to any one of [1] to [11], wherein the catechin is preferably at least 1 selected from the group consisting of catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate.

[13] The agent according to any one of [1] to [12], wherein the agent is preferably a pharmaceutical or quasi-pharmaceutical, and contains 0.1 to 20 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 1 to 20 mass%, 1 to 10 mass%, 1 to 5 mass%, 3 to 20 mass%, 3 to 10 mass%, or 3 to 5 mass% of the catechin.

[14] The agent according to [13], which preferably contains ornithine in an amount of 0.3 to 60 mass%, 0.3 to 30 mass%, 0.3 to 20 mass%, 0.3 to 15 mass%, 3 to 60 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 5 to 60 mass%, 5 to 30 mass%, 5 to 20 mass%, 5 to 15 mass%, 9 to 60 mass%, 9 to 30 mass%, 9 to 20 mass%, or 9 to 15 mass%.

[15] The agent according to any one of [1] to [12], wherein the agent is preferably a food and contains 0.05 to 10 mass%, 0.05 to 5 mass%, 0.05 to 1 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 0.1 to 1 mass%, 1 to 10 mass%, or 1 to 5 mass% of the catechins.

[16] The agent according to [15], which preferably contains ornithine in an amount of 0.15 to 30 mass%, 0.15 to 20 mass%, 0.15 to 15 mass%, 0.15 to 5 mass%, 0.15 to 3 mass%, 0.3 to 30 mass%, 0.3 to 20 mass%, 0.3 to 15 mass%, 0.3 to 5 mass%, 0.3 to 3 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 3 to 5 mass%, 5 to 30 mass%, 5 to 20 mass%, or 5 to 15 mass%.

[17] The agent according to any one of [1] to [16], wherein the mass ratio of the catechin to the ornithine is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, further preferably 1: 1 to 8, further preferably 1: 1 to 5, and further preferably 1: 2 to 4.

[18] The agent according to any one of [1] to [17], wherein the agent is preferably an oral agent.

[19] Use of catechins and ornithine for the manufacture of an ammonia metabolism promoter.

[20] Use of catechins and ornithine for the manufacture of an endurance improving agent.

[21] Use of catechins and ornithine for the manufacture of an anti-fatigue agent.

[22] Use of catechins and ornithine for producing an inhibitor for lowering blood glucose level due to exercise.

[23] Use of catechins and ornithine for producing a promoter for recovery from a decrease in blood glucose level due to exercise.

[24] Use of catechins and ornithine for the manufacture of an inhibitor of muscle glycogen reduction due to exercise.

[25] Use of catechins and ornithine for the manufacture of a promoter for recovery from muscle glycogen reduction due to exercise.

[26] Use of catechins and ornithine for the manufacture of a muscle endurance improver.

[27] Use of catechins and ornithine for producing a prophylactic or ameliorating agent for hyperammonemia.

[28] Use of catechins and ornithine for producing a prophylactic or ameliorating agent for hepatic encephalopathy.

[29] Use of catechins and ornithine for producing a prophylactic or ameliorating agent for chronic fatigue syndrome.

[30] The use according to any one of [19] to [29], wherein the catechin is preferably at least 1 selected from the group consisting of catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate.

[31] The use according to any one of [19] to [30], wherein the agent is preferably a pharmaceutical or quasi-pharmaceutical and contains 0.1 to 20 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 1 to 20 mass%, 1 to 10 mass%, 1 to 5 mass%, 3 to 20 mass%, 3 to 10 mass%, or 3 to 5 mass% of the catechin.

[32] The use according to [31], wherein the agent preferably contains 0.3 to 60 mass%, 0.3 to 30 mass%, 0.3 to 20 mass%, 0.3 to 15 mass%, 3 to 60 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 5 to 60 mass%, 5 to 30 mass%, 5 to 20 mass%, 5 to 15 mass%, 9 to 60 mass%, 9 to 30 mass%, 9 to 20 mass%, or 9 to 15 mass% of the ornithine.

[33] The use according to any one of [19] to [30], wherein the agent is preferably a food and contains 0.05 to 10 mass%, 0.05 to 5 mass%, 0.05 to 1 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 0.1 to 1 mass%, 1 to 10 mass%, or 1 to 5 mass% of the catechin.

[34] The use according to [33], wherein the agent preferably contains 0.15 to 30 mass%, 0.15 to 20 mass%, 0.15 to 15 mass%, 0.15 to 5 mass%, 0.15 to 3 mass%, 0.3 to 30 mass%, 0.3 to 20 mass%, 0.3 to 15 mass%, 0.3 to 5 mass%, 0.3 to 3 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 3 to 5 mass%, 5 to 30 mass%, 5 to 20 mass%, or 5 to 15 mass% of the ornithine.

[35] The use according to any one of [19] to [34], wherein the mass ratio of the catechin to the ornithine in the agent is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, further preferably 1: 1 to 8, further preferably 1: 1 to 5, and further preferably 1: 2 to 4.

[36] The use according to any one of [19] to [35], wherein the agent is preferably an oral agent.

[37] Use of catechins and ornithine for promoting ammonia metabolism.

[38] Use of catechins and ornithine for improving endurance.

[39] Use of catechins and ornithine for combating fatigue.

[40] Use of catechins and ornithine for inhibiting a decrease in blood glucose level due to exercise.

[41] Use of catechins and ornithine for promoting recovery from a decrease in blood glucose level due to exercise.

[42] Use of catechins and ornithine for inhibiting muscle glycogen reduction due to exercise.

[43] Use of catechins and ornithine for promoting recovery from muscle glycogen reduction due to exercise.

[44] Use of catechins and ornithine for improving muscle endurance.

[45] Use of catechins and ornithine for preventing or improving hyperammonemia.

[46] Use of catechins and ornithine for preventing or improving hepatic encephalopathy.

[47] Use of catechins and ornithine for preventing or improving chronic fatigue syndrome.

[48] The use according to any one of [37] to [47], wherein the catechin is preferably at least 1 selected from the group consisting of catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate.

[49] The use according to any one of [37] to [48], wherein the catechin and the ornithine are preferably used in the form of a pharmaceutical or quasi-pharmaceutical containing 0.1 to 20 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 1 to 20 mass%, 1 to 10 mass%, 1 to 5 mass%, 3 to 20 mass%, 3 to 10 mass%, or 3 to 5 mass% of the catechin.

[50] The use according to [49], wherein the pharmaceutical or quasi-pharmaceutical preferably contains 0.3 to 60 mass%, 0.3 to 30 mass%, 0.3 to 20 mass%, 0.3 to 15 mass%, 3 to 60 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 5 to 60 mass%, 5 to 30 mass%, 5 to 20 mass%, 5 to 15 mass%, 9 to 60 mass%, 9 to 30 mass%, 9 to 20 mass%, or 9 to 15 mass% of ornithine.

[51] The use according to any one of [37] to [48], wherein the catechin and the ornithine are preferably used in the form of a food containing 0.05 to 10 mass%, 0.05 to 5 mass%, 0.05 to 1 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 0.1 to 1 mass%, 1 to 10 mass%, or 1 to 5 mass% of the catechin.

[52] The use according to [51], wherein the food preferably contains 0.15 to 30 mass%, 0.15 to 20 mass%, 0.15 to 15 mass%, 0.15 to 5 mass%, 0.15 to 3 mass%, 0.3 to 30 mass%, 0.3 to 20 mass%, 0.3 to 15 mass%, 0.3 to 5 mass%, 0.3 to 3 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 3 to 5 mass%, 5 to 30 mass%, 5 to 20 mass%, or 5 to 15 mass% of the ornithine.

[53] The use according to any one of [37] to [52], wherein a mass ratio of the catechin to the ornithine is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, further preferably 1: 1 to 8, further preferably 1: 1 to 5, and further preferably 1: 2 to 4.

[54] The use according to any one of [37] to [53], wherein the catechin and the ornithine are preferably orally administered.

[55] A combination of catechins and ornithine for use in the promotion of ammonia metabolism.

[56] A combination of catechins and ornithine for use in an improvement of stamina.

[57] A combination of catechins and ornithine for use in combating fatigue.

[58] A combination of catechins and ornithine for use in inhibiting a decrease in blood glucose level due to exercise.

[59] A combination of catechins and ornithine for use in promoting recovery from a decrease in blood glucose level due to exercise.

[60] A combination of catechins and ornithine for use in the inhibition of muscle glycogen reduction due to exercise.

[61] A combination of catechins and ornithine for use in the promotion of recovery from muscle glycogen reduction due to exercise.

[62] A combination of catechins and ornithine for use in improving muscle endurance.

[63] A combination of catechins and ornithine for use in the prevention or amelioration of hyperammonemia.

[64] A combination of catechins and ornithine for use in the prevention or amelioration of hepatic encephalopathy.

[65] A combination of catechins and ornithine for use in the prevention or amelioration of chronic fatigue syndrome.

[66] The combination of a catechin and ornithine according to any one of [55] to [65], wherein the catechin is preferably at least 1 selected from the group consisting of catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate.

[67] The combination of a catechin and ornithine as recited in any one of [55] to [66], wherein the combination is preferably a pharmaceutical or quasi-pharmaceutical containing 0.1 to 20 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 1 to 20 mass%, 1 to 10 mass%, 1 to 5 mass%, 3 to 20 mass%, 3 to 10 mass%, or 3 to 5 mass% of the above catechin.

[68] The combination of catechins and ornithine as set forth in [67], wherein the pharmaceutical product or quasi-pharmaceutical product preferably contains 0.3 to 60% by mass, 0.3 to 30% by mass, 0.3 to 20% by mass, 0.3 to 15% by mass, 3 to 60% by mass, 3 to 30% by mass, 3 to 20% by mass, 3 to 15% by mass, 5 to 60% by mass, 5 to 30% by mass, 5 to 20% by mass, 5 to 15% by mass, 9 to 60% by mass, 9 to 30% by mass, 9 to 20% by mass, or 9 to 15% by mass of ornithine.

[69] The combination of a catechin and ornithine as recited in any one of [55] to [66], wherein the combination is preferably a food containing 0.05 to 10 mass%, 0.05 to 5 mass%, 0.05 to 1 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 0.1 to 1 mass%, 1 to 10 mass%, or 1 to 5 mass% of the above catechin.

[70] The combination of catechins and ornithine as set forth in [69], wherein the food preferably contains 0.15 to 30% by mass, 0.15 to 20% by mass, 0.15 to 15% by mass, 0.15 to 5% by mass, 0.15 to 3% by mass, 0.3 to 30% by mass, 0.3 to 20% by mass, 0.3 to 15% by mass, 0.3 to 5% by mass, 0.3 to 3% by mass, 3 to 30% by mass, 3 to 20% by mass, 3 to 15% by mass, 3 to 5% by mass, 5 to 30% by mass, 5 to 20% by mass, or 5 to 15% by mass of ornithine.

[71] The combination of catechins and ornithine according to any one of [55] to [70], wherein the mass ratio of the catechins to the ornithine is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, further preferably 1: 1 to 8, further preferably 1: 1 to 5, further preferably 1: 2 to 4.

[72] The combination of a catechin and ornithine as recited in any one of [55] to [71], wherein oral administration is preferred.

[73] The combination of catechins and ornithine according to any one of [55] to [72], wherein the amounts of catechins and ornithine to be administered per 1 day to 1 adult are as follows:

[ catechins ] are preferably 100 to 3000mg/60kg body weight, more preferably 250 to 2000mg/60kg body weight, still more preferably 250 to 1000mg/60kg body weight, and yet more preferably 250 to 600mg/60kg body weight;

[ ornithine (in terms of free body) ] is preferably 100 to 5000mg/60kg of body weight, more preferably 250 to 3000mg/60kg of body weight, even more preferably 400 to 2000mg/60kg of body weight, even more preferably 500 to 2000mg/60kg of body weight, even more preferably 800 to 1600mg/60kg of body weight, or preferably 250 to 800mg/60kg of body weight, even more preferably 500 to 800mg/60kg of body weight.

[74] The combination of catechins and ornithine as recited in [73], wherein the catechins and ornithine in the above-mentioned administration amounts are preferably administered 1 time per day, or 2 times or 3 times or more divided per 1 day.

[75] A method for promoting ammonia metabolism, which comprises administering a catechin and ornithine in effective amounts to a subject in need of ammonia metabolism promotion.

[76] A method for improving endurance, comprising the step of administering a catechin and ornithine in effective amounts to a subject in need of endurance improvement.

[77] An anti-fatigue method comprising the step of administering an effective amount of catechins and ornithine to a subject in need of anti-fatigue.

[78] A method for suppressing a decrease in blood glucose level due to exercise, which comprises administering an effective amount of catechins and ornithine to a subject in need of suppression of a decrease in blood glucose level due to exercise.

[79] A method for promoting recovery from a decrease in blood glucose level due to exercise, comprising the step of administering an effective amount of catechins and ornithine to a subject in need of promotion of recovery from a decrease in blood glucose level due to exercise.

[80] A method for inhibiting muscle glycogen reduction by exercise, which comprises the step of administering an effective amount of a catechin and ornithine to a subject in need of inhibition of muscle glycogen reduction by exercise.

[81] A method for promoting recovery from muscle glycogen reduction caused by exercise, which comprises the step of administering an effective amount of catechins and ornithine to a subject in need of promotion of recovery from muscle glycogen reduction caused by exercise.

[82] A method for improving muscle endurance, comprising the step of administering an effective amount of a catechin and ornithine to a subject in need of improvement in muscle endurance.

[83] A method for preventing or ameliorating hyperammonemia, which comprises the step of administering catechins and ornithine in an effective amount to a subject in need of prevention or amelioration of hyperammonemia.

[84] A method for preventing or ameliorating hepatic encephalopathy, which comprises the step of administering catechins and ornithine in an effective amount to a subject in need of prevention or amelioration of hepatic encephalopathy.

[85] A method for preventing or ameliorating chronic fatigue syndrome, comprising the step of administering catechins and ornithine in an effective amount to a subject in need of prevention or amelioration of chronic fatigue syndrome.

[86] The method according to any one of [75] to [85], wherein the catechin is preferably at least 1 selected from the group consisting of catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate.

[87] The method according to any one of [75] to [86], wherein a mass ratio of the catechin to the ornithine is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, further preferably 1: 1 to 8, further preferably 1: 1 to 5, and further preferably 1: 2 to 4.

[88] The method according to any one of [75] to [87], wherein the administration is preferably oral administration.

[89] The method according to any one of [75] to [88], wherein the amounts of the catechins and ornithine administered per 1 day to 1 adult human are as follows:

[ catechins ] are preferably 100 to 3000mg/60kg body weight, more preferably 250 to 2000mg/60kg body weight, still more preferably 250 to 1000mg/60kg body weight, and yet more preferably 250 to 600mg/60kg body weight;

[ ornithine (in terms of free body) ] is preferably 100 to 5000mg/60kg of body weight, more preferably 250 to 3000mg/60kg of body weight, even more preferably 400 to 2000mg/60kg of body weight, even more preferably 500 to 2000mg/60kg of body weight, even more preferably 800 to 1600mg/60kg of body weight, or preferably 250 to 800mg/60kg of body weight, even more preferably 500 to 800mg/60kg of body weight.

[90] The method according to [89], wherein the catechins and ornithine in the above-mentioned amounts are preferably administered 1 time a day, or 2 or 3 times or more divided into 1 day.

[91] A food for promoting ammonia metabolism contains catechin and ornithine as effective components.

[92] A food for improving endurance contains catechin and ornithine as effective components.

[93] An antifatigue food contains catechin and ornithine as effective components.

[94] A food for inhibiting blood sugar level decrease due to exercise contains catechin and ornithine as effective components.

[95] A food for promoting recovery from blood glucose level reduction due to exercise contains catechin and ornithine as effective components.

[96] A food for inhibiting muscle glycogen reduction caused by exercise contains catechin and ornithine as effective components.

[97] A food for promoting recovery from muscle glycogen reduction caused by exercise contains catechin and ornithine as effective components.

[98] A food for improving muscle endurance contains catechin and ornithine as effective components.

[99] A food for preventing or improving hyperammonemia contains catechin and ornithine as effective components.

[100] A food for preventing or improving hepatic encephalopathy comprises catechin and ornithine as effective components.

[101] A food for preventing or improving chronic fatigue syndrome contains catechin and ornithine as effective components.

[102] The food according to any one of [91] to [101], wherein the catechin is preferably at least 1 selected from the group consisting of catechin, gallocatechin, catechin gallate, gallocatechin gallate, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate.

[103] The food according to any one of [91] to [102], wherein the catechin is preferably contained in an amount of 0.05 to 10 mass%, 0.05 to 5 mass%, 0.05 to 1 mass%, 0.1 to 10 mass%, 0.1 to 5 mass%, 0.1 to 1 mass%, 1 to 10 mass%, or 1 to 5 mass%.

[104] The food according to [103], which preferably contains 0.15 to 30 mass%, 0.15 to 20 mass%, 0.15 to 15 mass%, 0.15 to 5 mass%, 0.15 to 3 mass%, 0.3 to 30 mass%, 0.3 to 20 mass%, 0.3 to 15 mass%, 0.3 to 5 mass%, 0.3 to 3 mass%, 3 to 30 mass%, 3 to 20 mass%, 3 to 15 mass%, 3 to 5 mass%, 5 to 30 mass%, 5 to 20 mass%, or 5 to 15 mass% of the ornithine.

[105] The food product according to any one of [91] to [104], wherein a mass ratio of the catechin to the ornithine is preferably 1: 0.1 to 10, more preferably 1: 0.5 to 10, further preferably 1: 1 to 8, further preferably 1: 1 to 5, and further preferably 1: 2 to 4.