JP2007204445A - Anti-fatigue composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe anti-fatigue composition having an anti-fatigue effect and attenuating chronic fatigue syndrome for preventing death by overworking, etc. <P>SOLUTION: This anti-fatigue composition for chronic fatigue is provided by containing at least 1 kind selected from acetic acid, acetate ion and acetic acid salt as an active ingredient. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an anti-fatigue composition for recovering or attenuating chronic fatigue.

  Fatigue is caused by muscular fatigue (hereinafter sometimes referred to as motor fatigue) caused by one-time intense exercise or physical labor, continuous long working hours or irregular work, and mental stress. There is chronic combined fatigue (hereinafter sometimes referred to as chronic fatigue).

  Chronic fatigue is often caused by work environment loads and mental stress, such as shift work, night work, long overtime, and holiday work, resulting in temporary physical and mental work capacity. As a result, not only does the efficiency of work decrease, but it also leads to occupational accidents and death from overwork, which is a social problem.

  Vitamin C (for example, see Non-patent Document 1) has been reported to be effective as a symptomatic treatment for chronic fatigue. However, the effect is not so strong, and an excellent anti-fatigue composition for chronic fatigue is proposed. It was desired to develop.

  However, the molecular and neurological mechanisms related to chronic fatigue are still unclear, and one of the causes is that although there are animal models of motor fatigue, the development of model animals of chronic fatigue is delayed. It was mentioned that.

  In contrast, the results of recent development of model animals for chronic fatigue (see, for example, Non-Patent Document 2), such as biopterin and related substances that are widely distributed in insects, amphibian skin, royal jelly, etc. An anti-fatigue composition for chronic fatigue containing a certain 6R-L-erythro-5,6,7,8-tetrahydrobiopterin has been proposed (see, for example, Patent Document 1).

  On the other hand, for acetic acid or vinegar, for example, ingestion of acetic acid together with glucose during exercise fatigue, replenishment of glycogen reduced by exercise is promoted in the liver and muscles. Although it has been reported to recover, knowledge about the effect on chronic fatigue is not disclosed (for example, see Non-Patent Document 3 and Non-Patent Document 4).

Patent Document 2 describes that an anti-fatigue composition containing coenzyme Q ₁₀ , carnitine and an organic acid is effective for chronic fatigue, and acetic acid is exemplified as the organic acid. Data are not shown. In addition, the anti-fatigue composition described in Patent Document 2 is effective due to the synergistic effect of the three components of coenzyme Q ₁₀ , carnitine and organic acid (paragraph 0056). This is based on the premise that a sufficient effect cannot be obtained (paragraphs 0005 to 0006). Further, also in Patent Document 3 and Patent Document 4 cited as the prior documents relating to the organic acid blended composition in Patent Document 2, the organic acid is limited to polycarboxylic acid (for example, citric acid, malic acid, tartaric acid). ing.

  Thus, the knowledge which suggests that acetic acid or another monocarboxylic acid has an effect with respect to chronic fatigue has not been reported until now.

JP 2005-15417 A JP-A-2005-97161 Japanese Patent Laid-Open No. 10-175856 JP-A-9-59161 “In Vivo”, Vol. 10, No. 6, p. 585-596, 1996 “Neuroscience Letters”, Volume 352, p. 159-162, 2003 “Journal of Nutrition (J. Nutr.)”, Vol. 131, No. 7, p. 1973-1977, 2001 “Int. J. Sports Med.”, Volume 23, p. 218-222, 2002

  The subject of this invention is providing the anti-fatigue composition used in order to recover or reduce chronic fatigue.

  The inventors of the present invention have recently been developed, focusing on the lack of an effective chronic fatigue model animal as one of the causes of the failure to find effective food ingredients and natural products that recover and attenuate chronic fatigue. At least selected from acetic acid, acetate ion and acetate salt using a water immersion breeding / load forced swimming test method (for example, see Patent Document 1 and Non-Patent Document 1), which is a model reflecting the process leading to overworked death due to fatigue. One type was found to have an excellent anti-fatigue effect, and the present invention was completed.

That is, the present invention is as follows.
(1) An anti-fatigue composition for chronic fatigue containing at least one selected from acetic acid, acetate ions and acetate as an active ingredient.
(2) The anti-fatigue composition according to (1), which is prepared so that at least one selected from 0.1 to 2 g (acetic acid equivalent amount) of acetic acid, acetate ions, and acetates can be ingested per day.
(3) anti-fatigue composition according to the not containing coenzyme _{Q 10} (1) or (2).
(4) The anti-fatigue composition according to any one of (1) to (3), which does not contain carnitine.
(5) The anti-fatigue composition according to any one of (1) to (4) for treating chronic fatigue syndrome.
(6) The anti-fatigue composition according to any one of (1) to (5) for preventing death from overwork.

  According to the present invention, by taking a pharmaceutical or food containing at least one selected from acetic acid, acetate ion and acetate, it is excellent against so-called chronic fatigue caused by daily chronic stress and work load. A recovery and attenuation effect can be expected.

The present invention will be described in detail below.
Acetic acid used in the present invention is not particularly limited in its production method, and may be produced by a synthesis method or produced by a fermentation method.

  However, when used as food, it is preferable to use acetic acid produced by fermentation because it is safer, that is, vinegar (brewed vinegar), especially brown rice vinegar and refreshing Apple cider vinegar having a good scent is more preferred.

  Various acetates such as sodium acetate can be used in that acetic acid can be ingested while reducing acidity.

The composition of the present invention may be referred to as non-dissociated acetic acid molecules (CH ₃ COOH), dissociated acetate ions (CH ₃ COO ⁻ ), and non-dissociated acetate (hereinafter referred to as “acetic acids”). ) As an active ingredient.

  This is because even if the acetic acid taken from the mouth is an acetic acid solution having a low pH, a neutralized acetate salt (for example, sodium acetate), or a dissociated acetate ion, these absorptions are not absorbed. The pH of the intestinal tract after the stomach and the small intestine is not affected so much by the composition of the composition and is kept almost constant at each site, so the presence of acetic acid in the composition at the stage of entering the mouth This is because the condition does not affect the absorption of acetic acid in the body.

  The measurement of acetic acid can be carried out using, for example, a carboxylic acid analyzer (EYELA carboxylic acid analyzer S-3000) manufactured by Tokyo Rika Kikai Co., Ltd. The analyzer is a device that detects organic acids by separating the various organic acids using a column and adopts the principle of reacting specifically with carboxyl groups, regardless of dissociation or non-dissociation. Can be quantified.

  The composition of the present invention can be used as pharmaceuticals and foods, and pharmaceuticals mean those stipulated in the Pharmaceutical Affairs Law, and are provided in all forms such as tablets, capsules, powders, granules, fine granules, and drinks. Is possible.

  In addition, food means what is taken orally, including functional foods, health supplements, functional nutritional foods, special-purpose foods, foods for specified health use, and other foods that can be administered orally. Conventional foods using vinegar such as sushi, marinade and vinegar drinks are also included.

  When the composition of the present invention is used as a food, a label such as recovery / attenuation of chronic fatigue, treatment of chronic fatigue syndrome, or recovery / attenuation of chronic combined fatigue, prevention of overwork death, etc. is attached. It is desirable to use it.

  The composition can be prepared by mixing an appropriate amount of at least one selected from acetic acid, acetate ions and acetate according to the type of the composition and other conventional raw materials (food raw materials, pharmaceutical raw materials). it can.

  For example, in the case of solid preparations, excipients, binders, disintegrants, fillers, fillers, humectants, surfactants, lubricants, etc. can be used. Turbidizing agents, buffering agents and the like can be used. If necessary, preservatives, solubilizers, emulsifiers, dispersants, thickeners, plasticizers, adsorbents, fragrances, colorants, flavoring agents, sweeteners, preservatives, antioxidants, etc. are also used. Is possible.

  Examples of the excipient include lactose, sucrose, oligosaccharide, maltitol, sorbitol, xylitol, mannitol and the like, and examples of the binder include crystalline cellulose, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, arabic. Examples include gum.

  Examples of the disintegrant include starch, carboxycellulose, and carboxymethylcellulose calcium. As the lubricant, magnesium stearate, calcium stearate, colloidal silica or the like is used.

  Examples of the solvent that can be used include physiological saline, alcohol, propylene glycol, macrogol, sesame oil, and corn oil. Examples of the solubilizer include ethanol and polyethylene glycol.

  Examples of the suspending agent include surfactants such as sodium lauryl sulfate, lecithin and glyceryl monostearate, and hydrophilic polymers such as polyvinyl alcohol, hydroxymethyl cellulose and hydroxymethylpropyl cellulose.

  Examples of the preservative include paraoxybenzoic acid ester, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid and the like.

  Examples of the coloring agent include tar dyes and titanium oxide. Examples of the flavoring agent include citric acid, adipic acid, ascorbic acid, and menthol. Examples of the antioxidant include sulfite and ascorbic acid. It is done.

  Furthermore, additives such as other physiologically active substances, minerals, vitamins, hormones, nutrients, and fragrances can be mixed as necessary.

  The method for adding acetic acid is not particularly limited and may be a general method. However, when acetic acid is used in the form of a low pH solution such as synthetic acetic acid or brewed vinegar instead of salt, Because of the problem of ease of eating and drinking, attention should be paid to “sourness” due to low pH. Specifically, when ingesting a low pH solution, problems such as soaking occur. Therefore, when acetic acids are contained at a high concentration, it is possible to take an aspect such as utilization and / or encapsulation of acetate.

  On the other hand, the dose of acetic acid according to the present invention, that is, the intake, may be determined depending on the recipient's sex, age, weight, and symptoms, administration time, dosage form, administration method, combination of drugs, etc. For example, 0.1 g to 2 g is preferably administered per person per day, more preferably 1 to 2 g.

  In this case, the number of intakes per day need not be limited to one, but can be divided into several times during the day.

  By the way, in animal experiments, an effect is seen by administering 0.01 to 0.02 g of acetic acid to rats, and when this result is converted to humans, a method of 10 to 100 times is generally used. Since it is adopted, it is considered that taking 1 to 2 g per person per day is effective.

  The concentration of acetic acid added to the composition is preferably about 0.1 to 2 g per 1 kg of the composition as an acetic acid equivalent amount. This is because if the concentration is lower than this, it is necessary to take a very large amount of a composition such as a drink or a tablet. Here, the amount that can be taken per day is calculated and set on the assumption that it is about 1 kg or 1 liter.

  Moreover, it is possible to ingest the necessary amount of effective acetic acid molecules by ingesting about 50 to 200 ml of drink containing vinegar such as apple vinegar per day.

  In addition, when using high-concentration and non-neutralized acetic acid, it is desirable to take an intake method that takes into account gastrointestinal tract disorders such as stomach and intestine.

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
Example 1
Seven-week-old male SD rats were bred for 5 days in cages with a water temperature of 23 ° C. ± 1 ° C. and a depth of 1.5 cm. From the first day, physiological saline (3 ml / day), ascorbic acid was intraperitoneally administered (30 mg / kg / day) or orally (300 mg / kg / day), and acetic acid was orally administered (30 mg / kg / day). ). The physiological saline intraperitoneal administration group was the control group (n = 12), the ascorbic acid intraperitoneal administration group was the positive control group (n = 8), the test group was the ascorbic acid oral administration group (n = 8), and acetic acid. Oral administration group (n = 12).

  Then, in order to examine the attenuation effect of chronic fatigue, after 24 hours from the administration on the 5th day, 8 of the saline intraperitoneal administration group (control group) (n = 12), ascorbic acid intraperitoneal administration 8 rats out of the group (positive control group) (n = 8), the ascorbic acid oral administration group (n = 8) and the acetic acid oral administration group (n = 12) were loaded with a weight of 8% of the body weight. The time until the nose is submerged for 10 seconds or more after swimming, and the average time of the physiological saline intraperitoneal administration group (control group) was taken as 100%, and the results representing the average time of each administration group Is shown in FIG.

  At the same time, in order to examine whether this test system shows a known glycogen supplementation promoting effect by acetic acid, 24 hours after the administration on the fifth day, the physiological saline intraperitoneal administration group (control group) (n = 12) 4) and the remaining 4 animals in the acetic acid oral administration group (n = 12) were dissected under ether anesthesia, and the liver and muscles (soleus muscle and gastrocnemius muscle) were immediately removed and the temperature was adjusted to -80 ° C. And saved. And the glycogen content in the tissue of each group was measured. The obtained results are shown in FIGS.

  From the results shown in FIG. 1, it was found that ascorbic acid and acetic acid enable longer swimming in the weight-load forced swimming test compared to the physiological saline intraperitoneal administration group (control group). Furthermore, ascorbic acid administration was confirmed to be less effective in the case of oral ingestion compared to intraperitoneal administration, whereas in the case of acetic acid, it was confirmed that long-term swimming was possible by oral administration.

  Furthermore, from the results of FIGS. 2 to 4, it was confirmed that there was no difference in the amount of glycogen in each tissue when water was ingested and when acetic acid was ingested. The glycogen replenishment effect of acetic acid observed in Patent Document 4) is different from the fact that carbohydrate is not ingested simultaneously with acetic acid, and it was confirmed that glycogen resupplementation is not accelerated in the present invention.

  That is, it was considered that the fatigue attenuation effects such as acetic acid, acetate ions, and acetates observed in the weight-load forced swimming test did not depend on the amount of glycogen stored in each organ. Based on the above, it was considered that acetic acid is effective in reducing fatigue without taking carbohydrates at the same time, and it is suitable for reducing chronic fatigue by oral ingestion, regardless of the form of intake. .

(Example 2)
In order to examine the effect of reducing chronic fatigue at different acetic acid concentrations, 7-week-old male SD rats were raised for 5 days in cages with a water temperature of 23 ° C. ± 1 ° C. and a depth of 1.5 cm. From the first day, physiological saline (3 ml / day), ascorbic acid was intraperitoneally administered (30 mg / kg / day) or orally (300 mg / kg / day), and acetic acid was orally administered (30 mg / kg / day). And 60 mg / kg / day).

  The physiological saline intraperitoneal administration group was the control group (n = 8), the ascorbic acid intraperitoneal administration group was the positive control group (n = 8), and the test group was the acetic acid low dose oral administration group (30 mg / kg / day). ) (N = 8) and acetic acid high dose oral administration group (60 mg / kg / day) (n = 8).

  Then, in order to investigate the attenuation effect of chronic fatigue, after 24 hours from the administration on the 5th day, the rats were allowed to swim with a weight of 8% of the body weight, and the nose was submerged for 10 seconds or more. FIG. 5 shows the average time of each administration group with the average time of the physiological saline intraperitoneal administration group (control group) as 100%.

  From the results of FIG. 5, when acetic acid was administered, it was possible to swim for a longer time than in the control group in both cases of oral administration of acetic acid at low doses and oral administration of acetic acid at high doses. It was confirmed that the effect more than that was demonstrated.

(Example 3)
A drink was prepared with the following composition. That is, 155 ml of apple vinegar, 100 ml of apple juice, 10 g of honey, 0.1 g of sucralose, 0.1 g of citric acid and 0.01 g of vitamin C are mixed and dissolved in 1 liter to prepare a drink containing about 7 g of acetic acid. did. The drink has a moderate sour taste and excellent drinkability, and drinks about 100 to 200 ml (0.7 to 1.4 g of acetic acid) per day due to the effect of acetic acid. It was considered possible and suitable for expecting fatigue reduction for chronic fatigue by oral intake.

Example 4
Tablets were produced with the following composition. That is, a tablet containing 2.5 g of sodium acetate per 100 g of tablet (50 mg per tablet) was produced. By ingesting 12 g (6 tablets, 0.3 g of acetic acid) of the tablet per day, fatigue attenuation against chronic fatigue can be expected.

It is a figure which shows the relative value of the average time required to submerge in the weight load forced swimming test in Example 1. It is a figure which shows the result of having measured the glycogen density | concentration of the liver in Example 1. FIG. It is a figure which shows the result of having measured the glycogen concentration of the soleus muscle in Example 1. FIG. It is a figure which shows the result of having measured the glycogen density | concentration of the gastrocnemius in Example 1. FIG. It is a figure which shows the relative value of the average time required to submerge in the weight load forced swimming test in Example 2. FIG.

Claims (6)

  An anti-fatigue composition for chronic fatigue containing at least one selected from acetic acid, acetate ions and acetate as an active ingredient.   The anti-fatigue composition of Claim 1 prepared so that at least 1 type chosen from the acetic acid of 0.1-2g (acetic acid conversion amount) per day, an acetate ion, and an acetate salt could be ingested. Anti-fatigue composition according to claim 1 or 2 containing no coenzyme Q _10.   The anti-fatigue composition according to any one of claims 1 to 3, which does not contain carnitine.   The anti-fatigue composition of any one of Claims 1-4 for treating chronic fatigue syndrome.   The anti-fatigue composition of any one of Claims 1-5 for preventing death from overwork.

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