JP2009155331A - Anti-fatigue agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an anti-fatigue agent using, as an active ingredient, fucoxanthin and/or fucoxanthin which are known to have functions such as a diabetes-improving action, a neovascularization-inhibiting action, and a DHA synthesis-promoting action, and is furthermore effective for reducing fatigues. <P>SOLUTION: This anti-fatigue agent comprises the fucoxanthin and/or fucoxanthin as an active ingredient. The fatigue is a phenomenon that a living body exhibits a function and consequently deteriorates the function. The anti-fatigue effect includes an action for reducing the fatigue state, an action for recovering the fatigue state, or an action for preventing the fatigue state. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an anti-fatigue agent useful for various diseases containing fucoxanthin as an active ingredient.

Fucoxanthin is known to have functions such as diabetes-improving action (Patent Document 1), angiogenesis-inhibiting action (Patent Document 2), and DHA synthesis promoting action (Patent Document 3).
However, it is not known that fucoxanthin has an anti-fatigue action described below.
JP 2007-314451 A JP 2008-1623 A JP 2007-77067 A

  An object of the present invention is to provide an anti-fatigue agent having an excellent anti-fatigue action.

  The present invention provides an anti-fatigue agent containing fucoxanthin and / or fucoxanthinol as an active ingredient.

ADVANTAGE OF THE INVENTION According to this invention, the anti-fatigue agent which has the outstanding anti-fatigue action can be provided. In addition, the fatigue in this invention means the phenomenon in which the function falls as a result of exhibiting a certain function. For example, “physical fatigue after swimming”, “mental fatigue after prolonged intellectual work”, “combined physical and mental fatigue that accumulates in everyday life”, etc. it can.
The anti-fatigue effect (nutrient tonic effect) referred to in the present invention includes an action of reducing the fatigue state as described above, an action of recovering the fatigue state, or an action of preventing the fatigue state.

  Hereinafter, the present invention will be described in more detail.

  Fucoxanthin and fucoxanthinol used in the present invention are known compounds, and their preparation methods are described in, for example, Patent Document 2. That is, the fucoxanthin used in the present invention can be derived from a natural product, for example, brown algae belonging to the order of the family Kombuaceae, Chigasiaceae, etc .; It can be extracted from microalgae such as diatoms.

The extraction method is performed, for example, by bringing a polar solvent such as a polar organic solvent or a mixture of water and a polar organic solvent into contact with a raw material. Examples of the polar organic solvent include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, butanol and isopropanol; propylene glycol; acetone; ethyl acetate; hexane; dichloromethane; chloroform alone or a combination of two or more. Can do.
In addition, it is preferable to dry and grind the raw material containing fucoxanthin prior to extraction.
The extraction method may be performed by a conventional method. For example, fucoxanthin can be extracted by adding 2 to 100 times the above-described extraction solvent to the raw material, and subjecting the raw material to immersion treatment and stirring treatment.

  It is preferable to remove the organic solvent from the extracted fucoxanthin by vacuum distillation or the like. It can also be applied to various known purification methods. If necessary, it can be further subjected to a drying treatment such as reduced pressure drying, freeze drying, spray drying and the like. In the present invention, various commercially available fucoxanthins can also be used.

  Fucoxanthinol is a hydrolyzed fucoxanthin and is known. The hydrolysis reaction can be achieved by, for example, fucoxanthin using a lipolytic enzyme such as lipase or cholesterol esterase.

  The dose of fucoxanthin and / or fucoxanthinol varies depending on the patient's age, body weight, indication symptoms, etc., for example, about 1 mg to 1 g, preferably about 3 mg to 300 mg per day for adults as lyophilized powder. It is good to do.

  The anti-fatigue agent of the present invention can be appropriately prepared by a known method in the form of a solid or solution (hereinafter also referred to as a preparation) such as tablets, pills, capsules, granules, powders, powders, and liquids. That is, the solid preparation or liquid preparation useful in the present invention is produced by using a well-known preparation method that has been well established. Examples of additives include excipients, pH adjusting agents, cooling agents, suspending agents, diluents, antifoaming agents, thickeners, solubilizers, disintegrating agents, binders, lubricants, antioxidants. Agents, coating agents, coloring agents, flavoring agents, surfactants, plasticizers or fragrances.

  The anti-fatigue agent of the present invention can be taken as various health foods and functional foods. Examples of these include various products, but for the production of health foods and functional foods, in addition to commonly used food materials and food additives, excipients, extenders, binders, It can be used in the form of food and drink preparations using adjuvants such as disintegrants, lubricants, dispersants, preservatives, wetting agents, solubilizers, preservatives, stabilizers, capsule bases and the like. Specific examples of the adjuvant include lactose, fructose, glucose, starch, gelatin, magnesium carbonate, synthetic magnesium silicate, talc, magnesium stearate, calcium carbonate, methylcellulose, carboxymethylcellulose, or a salt thereof, gum arabic , Polyethylene glycol, syrup, petrolatum, glycerin, ethanol, propylene glycol, citric acid, sodium chloride, sodium sulfite, sodium phosphate, pullulan, carrageenan, dextrin, reduced palatinose, sorbitol, xylitol, stevia, synthetic sweetener, citric acid Ascorbic acid, acidulant, baking soda, sucrose ester, hardened vegetable oil, potassium chloride, safflower oil, beeswax, soybean lecithin, flavor, and the like can be blended. Regarding the production of such health foods and functional foods, reference books for pharmaceutical preparations such as “Japanese Pharmacopoeia Manual (General Rules for Preparations)” (Yodogawa Shoten) can be referred to.

  In addition to the above, the anti-fatigue agent of the present invention can be taken as a food or drink. Specifically, natto, thick fried, tofu, konjac, dumplings, pickles, boiled, croquettes, sandwiches, pizzas, hamburgers, dumplings, shumai, salads, etc., various powders (beef, pork, chicken and other livestock products) Marine products such as shrimp, scallops, sea bream, kelp, vegetables / fruits, plants, yeast, algae, etc.), pudding, cookies, crackers, bread, cakes, chocolate, potato chips, biscuits, donuts, jellies and other confectionery, Japanese rice crackers such as rice crackers, sheep crab, daifuku, ohagi, other buns, Japanese confectionery such as castella, frozen confectionery (rice cake etc.), bread and confectionery such as chewing gum, noodles such as udon, buckwheat and kishimen, kamaboko, ham, fish sausage, etc. Fish paste products, meat products such as ham, sausage, hamburger, corn beef, salt, pepper, miso, soy sauce, sauce, dressy Seasonings such as gyu, mayonnaise, ketchup, sweeteners, spices, teppanyaki foods such as Akashi-yaki, takoyaki, monja-yaki, okonomiyaki, yakisoba, fried udon, dairy products such as cheese, hard-type yogurt, and fats and oils Various foods such as powdered solids of flavors and fragrances (vanilla, citrus fruits, bonito etc.) and powdered foods and drinks (instant coffee, instant tea, instant milk, instant soup, miso soup, etc.) These are not particularly limited.

  Furthermore, in the present invention, for example, royal jelly, propolis, vitamins (A, C, D, E, K, folic acid, pantothenic acid, biotin, derivatives thereof, etc.), minerals (iron, magnesium, calcium, zinc, etc.), Selenium, lecithin, carotenoids (lycopene, astaxanthin, zeaxanthin, lutein, etc.), saponins (gymnemic acid, soybean saponin, ginseng saponins, etc.), fatty acids, proteins (collagen, elastin, etc.), oligosaccharides (isomalto-oligosaccharides, cyclic oligosaccharides, etc.) ), Phospholipids and derivatives thereof (phosphatidylcholine, sphingomyelin, ceramide, etc.), sulfur-containing compounds (eg, alliin, sepaene, taurine, glutathione, methylsulfonylmethane), sugar alcohols, lignans (sesamin, etc.), Contains animal and plant extracts Root vegetables (turmeric, ginger, etc.), may be used in combination and the like.

EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not limited to these.
Preparation Example Fucoxanthin and fucoxanthinol were prepared according to the method described in Patent Document 2 above. The method is shown below.
1L of acetone: methanol (7: 3, v / v) was added in several batches to commercially available dried seaweed powder (dry weight about 100g) that was pulverized with a pulverizer. A fraction was obtained. After removing the solvent with an evaporator and dissolving in 100 mL of methanol, 100 mL of hexane and 10 mL of water were added, and liquid-liquid distribution was performed using a separatory funnel.

  The upper layer of the obtained solution was removed, and the lower layer was washed twice with 100 mL of hexane. Thereafter, 31 mL of water was added to the lower layer to make the ratio of methanol 70%, and then 100 mL of hexane was added for distribution. Furthermore, after concentrating the lower layer with an evaporator until the volume became 1/3, 150 mL of diethyl ether and 100 mL of water were added and distributed.

The upper layer (ether layer) was collected, the solvent was removed by an evaporator, and the obtained extract was subjected to thin layer chromatography (developing solvent = hexane: acetone (6: 4, v / v); PLC plate (15 PLC plates 20 × 20 cm, Silica gel 60 F254, 1 mm, Merck Ltd., Japan)).
The separated carotenoid fraction was scraped off from the plate and extracted again to obtain a carotenoid extract.

The carotenoid extract obtained above is subjected to HPLC, a fraction of the peak portion of fucoxanthin appearing at a measurement wavelength of 444 nm and a retention time of 8.7 minutes is fractionated, and the fraction thus fractioned with dichloromethane and Extraction with water was purified. The HPLC conditions are as shown below. When fucoxanthin was dissolved in acetone and calculated using the specific absorbance as a concentration, about 11 mg of fucoxanthin was obtained. This was freeze-dried to obtain powder 1 used in the following examples.
(HPLC preparative conditions)
・ Flow rate 1.0mL / min
・ Column temperature 40 ℃
Mobile phase (A) acetonitrile: methanol: water = 75: 15: 10 (v / v / v, containing 0.1% ammonium acetate) and (B) ethyl acetate: methanol = 30: 70 (v / v, 2-component gradient with 0.1% ammonium acetate)

  Further, fucoxanthin obtained as described above was enzymatically degraded using cholesterol esterase to obtain fucoxanthinol.

Example 1
STD DDY male mice (5 weeks old: each group n = 3 to 4) were orally ingested with xanthoangelol powder (hereinafter referred to as powder 1). The intake is 10 mg / kg body weight. Ingestion was performed using a solution in which powder 1 was dissolved in pure water. In addition, the test group mice were fed with pure water only.

Thirty minutes after the ingestion, the mouse was placed in an 80 cm deep water tank, and the time until immobility was measured. As an average value of time until mice of each test group (n = 3 to 4) reached immobility, the control group was about 100 seconds, while the powder 1 administration group was about 395 seconds. there were.
From the above, it was confirmed that the powder 1 has a high anti-fatigue effect.

Example 2
Twelve volunteer men (age 34-37) were grouped into a test meal group (Example) and a placebo group (Comparative Example). The test meal group (Example) is a group in which the powder 1 is processed into a soft capsule based on olive oil and 100 mg of the powder 1 is ingested every day. The placebo group (comparative example) is a group in which soft capsules containing olive oil without powder 1 are ingested daily.
Volunteer men were exercised with a bicycle ergometer at 5 and 9 weeks after ingestion. The exercise continues for 30 minutes at an exercise intensity of 80% load of the maximum heart rate.
The blood lactate levels of volunteer men immediately before and after exercise were measured with a commercially available simple blood lactate analyzer, and the amount of blood lactate increased was examined.
As a result, the increase after 5 weeks from the start of ingestion was about 6 mmol / l in the comparative example, whereas it was about 5.2 mmol / l in the example.
The increase after 9 weeks from the start of ingestion was about 6 mmol / l in the comparative example, whereas it was about 4.7 mmol / l in the example.
From the above, the anti-fatigue action of the powder 1 was clarified.

  In each of the above examples, when the fucoxanthinol powder was used instead of the powder 1, the same result as above was obtained. The anti-fatigue agent of the present invention is also useful as a feed form.

The compounding example of the anti-fatigue agent of this invention is shown below.
Candy sugar 50.0wt%
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Anti-fatigue agent of the present invention Total remaining amount 100.0 wt%

Yogurt milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Anti-fatigue agent of the present invention 0.4
Perfume Trace water Residue
Total 100.0wt%

Soft drink fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Anti-fatigue agent of the present invention 0.3
Perfume Appropriate amount of water Residual
Total 100.0wt%

Claims (1)

  An anti-fatigue agent containing fucoxanthin and / or fucoxanthinol as an active ingredient.