JP2014122210A - Vitamin b1 derivative composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition having fatigue prevention and/or recovery action.SOLUTION: A composition for fatigue prevention and/or recovery contains components (A) and (B), where the (A) is dicethiamine and/or salt thereof and the (B) is aspartic acids and/or thioctic acids.

Description

The present invention relates to a composition having a preventive and / or recovery action against physical fatigue and / or mental fatigue. More specifically, the present invention relates to a composition having fatigue prevention and / or recovery action, characterized by containing a vitamin B ₁ derivative.

  In recent years, the population suffering from fatigue has been increasing year by year. Fatigue is defined as "a state of reduced physical activity with excessive physical and mental activity, or a unique discomfort and desire for rest caused by illness" (Non-Patent Document 1). Is classified into physical fatigue and mental fatigue. Since such fatigue not only lowers QOL, but also causes a decline in immunity and may lead to unexpected diseases, etc., provision of a composition having excellent fatigue prevention and / or recovery action is desired. ing.

  Physical fatigue is directly caused by physical load such as exercise load, and sufficient rest is required for recovery. On the other hand, it has been suggested that mental fatigue is caused by the accumulation of oxidative stress in the central nervous system, including the brain, caused by environmental stress, and the failure of the bioreduction system that eliminates oxidative stress. It has been clarified that it causes the spread of fatigue such as chronic fatigue syndrome (Non-patent Document 2). In order to recover mental fatigue, it is said that it is necessary to reduce oxidative stress and maintain nerve function in a normal state (Non-patent Document 3).

Pharmaceutical compositions are provided containing vitamin B ₁ as a pharmaceutical composition for the amelioration of symptoms of fatigue including physical fatigue and / or mental fatigue. One such vitamin B ₁ derivative, dicetiamine, is well absorbed from the digestive tract, and is converted into vitamin B ₁ in vivo, and when pyruvic acid generated via the glycolysis system is converted to acetyl CoA. It is known to act as a coenzyme and is one of the most important factors for the normal metabolism of the TCA cycle. Specifically, supplementation when food intake is inadequate (eg, debilitating diseases, hyperthyroidism, pregnant women, lactating women, and severe physical fatigue), Wernicke encephalitis, leg stigma, neuralgia, muscle It is used for pain, joint pain, peripheral neuritis, peripheral nerve palsy, central nervous system disorder, myocardial metabolic disorder and gastrointestinal motor dysfunction due to constipation. More specifically, a physical fatigue recovery agent containing ubidecarenone and a vitamin B ₁ derivative (Patent Document 1), a fatigue recovery drug containing adenosine 5′-triphosphate and a vitamin B group (Patent Document 2), and aceto acetaminophen, vitamin B ₁ derivatives, solid preparation comprising magnesium stearate and amino acid salts (Patent Document 3) are known.

  Aspartic acid, on the other hand, promotes energy production as a substrate for oxaloacetate contained in the TCA cycle, and increases the efficiency of energy production by transporting deficient salts (such as calcium and magnesium) into cells. It is known that there is. Specifically, a composition for improving eye strain containing aspartic acid, garlic chemicals and vitamin B group is known (Patent Document 4).

Further, thioctic acid (aka: alpha-lipoic acid), in the TCA cycle, acts as a coenzyme in the same site as vitamin B _1, as its physiological action has the effect of promoting energy consumption of glucose in the metabolism . Specifically, a pharmaceutical product containing a predetermined amount of thioctic acid, dihydrolipoic acid, a metabolite thereof, an optical isomer of thioctic acid, and at least one salt is known (Patent Documents 5 and 6).

However, in any of the above-mentioned known documents, there is no disclosure or suggestion that a synergistic effect is exerted in fatigue prevention and / or recovery action by combining the following components (A) and (B).
(A) Dicetiamine and / or its salt (B) Aspartic acids and / or thioctic acids

Japanese Patent Laid-Open No. 10-287560 Japanese Patent No. 5032310 Japanese Patent No. 4573542 JP 2011-63580 A Japanese Patent Laid-Open No. 6-135832 JP-T-2004-508399

Antifatigue Clinical Evaluation Guidelines 5th Edition, Japan Society for Fatigue Fatigue and Non-Disease-Molecular Mechanism of Fatigue, History of Medicine, 198 (3), 2001 Oxidative stress and brain fatigue, medical history, 204 (5), 2003

  The present invention provides a composition having a synergistic prevention and / or recovery action against physical fatigue and / or mental fatigue.

As a result of diligent investigations to solve the above problems, the present inventors surprisingly found that when dicetiamine and / or a salt thereof and aspartic acid and / or thioctic acid were used in combination, they were used alone. As a result, it was found that a synergistic fatigue prevention and / or recovery action can be achieved, and the present invention has been completed.

That is, the present invention
(1) The following components (A) and (B)
(A) discetiamine and / or a salt thereof (B) a composition for fatigue prevention and / or recovery comprising aspartic acids and / or thioctic acids,
(2) The composition according to the above (1), wherein the component (A) is dicetiamine hydrochloride,
(3) The composition according to (1) or (2) above, wherein component (B) is L-aspartic acid and / or a salt thereof,
(4) The composition according to (1) or (2) above, wherein component (B) is potassium L-aspartate and / or magnesium,
(5) The composition according to any one of (1) to (4), wherein the thioctic acid is thioctic acid amide;
(6) A composition for preventing and / or recovering from fatigue, comprising discetiamine hydrochloride, potassium L-aspartate and magnesium L-aspartate,
About.

  The composition of the present invention has an extremely excellent fatigue prevention and / or recovery action due to the synergistic effect of component (A) discetiamine and / or a salt thereof and component (B) aspartic acids and / or thioctic acids, It can exhibit an excellent preventive and / or recovery action against physical fatigue and / or mental fatigue.

It is a figure which shows swimming time (second) in the dicetiamine hydrochloride 10 mg / kg, aspartic acid 100 mg / kg, and its combination administration group. It is a figure which shows the swimming time (second) in the dicethiamine hydrochloride 30 mg / kg, thioctic acid amide 10 mg / kg, and its combination administration group.

  The composition of the present invention is a composition for preventing and / or recovering from fatigue, comprising a combination of component (A) dicetiamine and / or a salt thereof and component (B) aspartic acid and / or thioctic acid. It is.

The composition of the present invention is provided as a combination of a preparation of a unit dosage form containing component (A) discetiamine and / or a salt thereof and a preparation of a unit dosage form containing component (B) aspartic acids and / or thioctic acids. Alternatively, it is provided as a composition in unit dosage form comprising component (A) and component (B) together. Preferably, it is provided as a unit dosage form composition comprising component (A) and component (B) together.

In the present invention, “discetiamine and / or a salt thereof” includes not only dicetiamine itself but also a salt thereof (for example, inorganic acid salt such as nitrate, hydrochloride, sulfate, etc.), which are used alone or in combination of two or more. Can be used in combination. In the present invention, dicetiamine hydrochloride is preferred. These “discetiamine and / or salt thereof” are known compounds, commercially available ones may be used, and they can also be produced by known methods.

The content of “discetiamine and / or a salt thereof” in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use and the like of the composition. For example, in the case of a composition for oral administration, a total of about 1 to 500 mg, preferably about 1 to 300 mg, more preferably about 5 to 150 mg of “discetiamine and / or a salt thereof” per day should be contained. Can do.

In the present invention, the ratio of “discetiamine and / or a salt thereof” with respect to the total mass of the composition is not particularly limited. The content is preferably 30% by mass, more preferably 0.1 to 20% by mass, and even more preferably 0.5 to 15% by mass.

In the present invention, “aspartic acids” include not only aspartic acid free form but also L-aspartic acid, D-aspartic acid and salts thereof (for example, sodium salt, potassium salt, calcium salt, magnesium salt, etc.) These can be used alone or in combination of two or more. In the present invention, a mixture of a potassium salt of aspartic acid and a magnesium salt of aspartic acid is preferred, a mixture of a potassium salt of L-aspartic acid and a magnesium salt of L-aspartic acid is more preferred, and a potassium salt of L-aspartic acid and Even more preferred is a mixture of equal amounts of the magnesium salt of L-aspartic acid. These “aspartic acids” are known compounds, which may be commercially available, or can be produced by known methods. The potassium salt of aspartic acid and the magnesium salt of aspartic acid are free forms of aspartic acid in an aqueous solution.

The content of “aspartic acid” in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use and the like of the composition. For example, in the case of a composition for oral administration, the amount of aspartic acids per day can be contained in a total amount of about 1 to 4000 mg, preferably about 5 to 1000 mg, more preferably about 5 mg to 500 mg.

In the present invention, the ratio of “aspartic acid” to the total composition weight is not particularly limited, and for example, it is preferable to contain “aspartic acid” in a total of 0.1 to 60% by mass with respect to the total composition mass, It is more preferable to contain 5-50 mass%, and it is still more preferable to contain 10-40 mass%.

  The content ratio of the component (A) dicethiamine and / or a salt thereof and “aspartic acids” in the composition of the present invention is not particularly limited, but with respect to a total of 1 part by mass of the component (A) dicethiamine and / or a salt thereof, The total amount of “aspartic acids” is preferably 0.5 to 400 parts by mass, more preferably 2 to 20 parts by mass, and even more preferably 3 to 15 parts by mass.

In the present invention, “thioctic acids” include thioctic acid and its derivatives, or salts thereof, which can be used alone or in combination of two or more. In the present invention, thioctic acid amide is preferred. These “thioctic acids” are known compounds, commercially available ones may be used, and they can be produced by known methods.

The content of “thioctic acids” in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use and the like of the composition. For example, in the case of a composition for oral administration, the total amount of thioctic acids per day may be about 0.05 to 300 mg, preferably about 1 to 200 mg, more preferably about 5 mg to 100 mg.

In the present invention, the ratio of “thioctic acids” to the total mass of the composition is not particularly limited. For example, the total amount of “thioctic acids” relative to the total mass of the composition is 0.01 to 60 masses. %, Preferably 0.1 to 30% by mass, more preferably 0.5 to 10% by mass.

  The content ratio of the component (A) dicetiamine and / or salt thereof and the “thioctic acid” in the composition of the present invention is not particularly limited, but with respect to a total of 1 part by mass of the component (A) dicetiamine and / or salt thereof, The total amount of “thioctic acids” is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and still more preferably 0.3 to 3 parts by mass.

The composition of the present invention may be any composition suitable for oral administration or parenteral administration. A composition suitable for oral administration is preferred. A composition suitable for oral administration is a solid, semi-solid, or liquid composition comprising component (A) dicetiamine and / or a salt thereof and component (B) aspartic acids and / or thioctic acids in one unit dosage form. More preferably, it is provided as a composition.

In providing the composition of the present invention as a composition suitable for oral administration or a composition suitable for parenteral administration, the dosage form is not particularly limited. For example, powders, granules, tablets, chewable tablets, film-coated tablets, sugar-coated tablets, soft capsules, hard capsules and other solid form compositions, drinks and other solution form compositions, jelly preparations, etc. Any of the compositions in a semi-solid form may be used. In the present invention, a composition in a solid form is preferable from the viewpoint of stability and ease of drinking.

When the composition of the present invention is provided as a composition containing component (A) dicetiamine and / or a salt thereof and component (B) aspartic acid and / or thioctic acid, the amount of each component in the composition is not particularly limited. It is determined according to the form of the composition composition in consideration of the combination ratio described above as appropriate. For example, in providing as a composition in a solid form, a total of about 10 to 200 mg of component (A) dicetiamine and / or a salt thereof and a total of about 10 to 600 mg of aspartic acids and / or thioctic amide can be blended.

In the composition of the present invention, components other than component (A) dicetiamine and / or a salt thereof and component (B) aspartic acids and / or thioctic acids can be appropriately blended according to the blending purpose. Ingredients that can be added as appropriate include vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin A, water-soluble vitamins, vitamin D, vitamin E, vitamin-like substances, carotenoids, minerals, caffeine other than dicetiamines Amino acids, drugs for liver damage, herbal medicines, other ingredients, and the like.

Vitamin B ₁ other than dicetiamines includes bisthiamine, thiamine disulfide, thiamine dicetyl sulfate ester, benfotiamine, prosultiamine, fursultiamine, bisbenchamine, chicotiamine, octothiamine, alitiamine, thiaminepropyl disulfide, thiamine Tetrahydrofurfuryl disulfide, bisbutyamine, bisbutiamine, thiamine monophosphate disulfide, thiamine pyrophosphate, chicotiamine, thiamine ethyl disulfide, thiamine propyl disulfide and their salts (for example, thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, fursultiamine hydrochloride, etc.) Hydrochloride, nitrate) and the like.

Examples of vitamin B ₂ include flavin adenine dinucleotide sodium, riboflavin, riboflavin sodium phosphate, and riboflavin butyrate.

Examples of vitamin B ₆ include pyridoxine, pyridoxal and salts thereof (hydrochlorides such as pyridoxine hydrochloride, phosphates such as acetate and pyridoxal phosphate).

The vitamin B _12, mecobalamin, cyanocobalamin, hydroxocobalamin, methylcobalamin and salts thereof (hydrochloride salt, acetic acid salt such as acetate hydroxocobalamin), and the like.

Examples of vitamin A include retinol acetate, retinol palmitate, vitamin A oil, liver oil, and strong liver oil.

Examples of water-soluble vitamins include ascorbic acid, calcium ascorbate, sodium ascorbate, nicotinic acid, nicotinic acid amide, panthenol, calcium pantothenate, sodium pantothenate, panthetin, biotin, folic acid and the like.

  Examples of vitamin D include ergocalciferol and cholecalciferol.

Examples of vitamin E include d-α-tocopherol succinate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, d-α-tocopherol acetate,
Examples include dl-α-tocopherol acetate, d-α-tocopherol, and dl-α-tocopherol.

Examples of vitamin-like substances include inositol, inositol hexanicotinate, orotic acid, choline orotate, gamma-oryzanol, thioctic acid, thioctic acid amide, carnitine chloride, ubidecarenone, choline bitartrate, rutin and the like.

  Carotenoids include carotenes such as α-carotene, β-carotene, lycopene, phytoene and their epoxies, or astaxanthin, zeaxanthin, lutein, cryptoxanthine, tunaxanthin, salmoxanthine, parasiloxanetin, violaxanthin, anthaxanthin , Cucurbitaxanthin, diatoxanthine, alloxanthin, pectinol, pectinolone, mctraxanthine, capsanthin, capsanthinol, fucoxanthin, fucoxanthinol, peridinin, halocinthiaxanthine, amaranthiaxanthine, canthaxanthin, echinenone, Examples thereof include xanthophylls such as rhodoxanthin, bixin and norbixin, and norcarotenoids and apocarotenoids.

Examples of minerals include calcium citrate, calcium glycerophosphate, sodium gluconate, magnesium carbonate, calcium carbonate, calcium gluconate, precipitated calcium carbonate, calcium lactate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, sodium chondroitin sulfate, and the like. .

Examples of caffeine include caffeine, caffeine derivatives such as anhydrous caffeine and sodium benzoate caffeine.

  As amino acids, L-cysteine hydrochloride, L-cysteine, aminoacetic acid, L-isoleucine, arginine hydrochloride, lysine hydrochloride, L-glutamic acid, L-threonine, L-valine, L-histidine hydrochloride, L-leucine, DL- Examples include methionine, L-phenylalanine, and L-tryptophan.

Drugs for liver damage include ursodeoxycholic acid, dehydrocholic acid, glucuronolactone, glucuronic acid, glucuronic acid amide, glycyrrhizic acid, sodium glycyrrhizinate, aminoethylsulfonic acid, diisopropylamine dichloroacetate, methylmethioninesulfonium chloride, Examples include liver hydrolyzate and yolk lecithin.

Herbal medicines include Azalea, Fennel, Ezoukogi, Ougi, Ousei, Guarana, Kanzo, Kokushi, Keihi, Kojin, Saffron, Hawthorn, Sanyaku, Peonies, Shukusha, Gyoza, Jotei, Hawthorn, Taiso, Clove, Chimpi,
Examples include Toki, Toshi, Tochu, Nikujuyo, Carrot, Bukkyou, Muirapuama, Mokko, Yakuchi, Yokuinin, Ryogannik, Royal Jelly, Lokjo and the like.

  Examples of other components include placenta.

  The composition in the present invention can be appropriately prepared by a technique commonly used in the art. In this case, you may use 1 type (s) or 2 or more types of the additives for a formulation normally used in this industry as needed. Examples of the additives for preparation include excipients, binders, disintegrants, lubricants, coloring agents, corrigents, film bases, surfactants, flavoring agents, flavoring agents, sweetening agents, sour agents, and the like. It can be mentioned, but is not limited to these.

  As the excipient, excipients listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Pharmaceuticals or the Standards for Pharmaceutical Additives, etc. can be used. Specifically, crystalline cellulose, microcrystalline cellulose, lactose, sucrose, purified sucrose, glucose, hydrous glucose, sucrose, maltose, powdered sugar, erythritol, maltitol, mannitol, D-mannitol, sucralose, trehalose, sorbitol, xylitol, Erythritol, D-sorbitol, lactose, maltose, maltose, flour, starch, pregelatinized starch, partially pregelatinized starch, dextrin, corn starch, hydroxypropyl starch, potato starch, wheat starch, rice starch, silicic anhydride, light anhydrous Silicic acid, magnesium carbonate, calcium carbonate, precipitated calcium carbonate, calcium silicate, calcium phosphate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, calcium sulfate, anhydrous Calcium oxide, synthetic aluminum silicate, magnesium aluminate metasilicate, magnesium oxide, titanium oxide, talc, L-cysteine, silicon dioxide, aspartame, glycyrrhizic acid and its salt, saccharin and its salt, stevia and its salt, gelatin, powder Reduced maltose syrup and tartaric acid.

  As the binder, binders listed in Japanese Pharmacopoeia, Japanese Pharmacopoeia Pharmaceutical Standards or Pharmaceutical Additives Standard, etc. can be used. Specifically, starch, pregelatinized starch, partially pregelatinized starch, gum arabic, gum arabic powder, gum arabic powder, sodium alginate, carboxymethylcellulose, sodium carboxymethylcellulose, sucrose, gelatin, dextrin, hydroxyethylcellulose, hydroxypropylcellulose Hydroxypropylmethylcellulose, pullulan, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, crystalline cellulose.

  As the disintegrant, disintegrants listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Pharmaceuticals or the Standards for Pharmaceutical Additives, etc. can be used. Specifically, carmellose, carmellose calcium, carmellose sodium, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, croscarmellose, croscarmellose sodium, crospovidone, starches (eg, partially pregelatinized starch, potato starch) Corn starch, hydroxypropyl starch, sodium carboxymethyl starch, low substituted sodium carboxymethyl starch, etc.), calcium carbonate, polyvinyl alcohol and the like.

  As the lubricant, lubricants listed in Japanese Pharmacopoeia, Japanese Pharmacopoeia Standards for Pharmaceuticals or Pharmaceutical Additives Standard, etc. can be used. Specific examples include talc, stearic acid, metal stearate (eg, magnesium stearate), sodium stearyl fumarate, colloidal silica, polyethylene glycol, and sucrose fatty acid ester.

  As the colorant, a colorant listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Pharmaceutical Standards or the Pharmaceutical Additives Standard, etc. can be used. Specifically, β-carotene, tar pigment, phenolphthalein, bengara, lycopene, riboflavin, riboflavin organic acid ester (for example, riboflavin butyrate ester), riboflavin phosphate or its alkali metal, alkaline earth metal salt, yellow sesquioxide Iron (yellow bengara), iron sesquioxide (red bengara), synthetic colorants (such as sunset yellow and their aluminum lakes), titanium oxide, edible yellow No. 5, edible red No. 2, edible blue No. 2, etc. Edible pigments and edible lake pigments.

  Any film base may be used as long as it can use a film base listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Pharmaceutical Standards, or the Pharmaceutical Additives Standard. Generally, a water-soluble coating or an enteric coating is used. Any polymeric substance may be used as long as it is used in a sustained release coating or the like. Examples of such high molecular substances include hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, ethylcellulose and other cellulosic bases, methacrylic acid copolymers Acrylic acid bases such as LD (Eudragit L30D-55), aminoalkyl acrylate copolymer E, aminoalkyl methacrylate copolymer RS, vinyl bases such as polyvinyl acetal diethylaminoacetate, and natural products such as shellac are used.

  When film coating is performed, the film base includes, for example, polyethylene glycol, glycerin fatty acid esters, sucrose fatty acid esters, castor oil, triethyl citrate, triacetin and other plasticizers, talc and other suspension agents, oxidation A hiding agent such as titanium, a colorant such as yellow iron sesquioxide and iron sesquioxide, a solvent such as ethyl alcohol and water, a pigment, and the like can be further blended.

  As the surfactant, surfactants listed in Japanese Pharmacopoeia, Japanese Pharmacopoeia Pharmaceutical Standards or Pharmaceutical Additive Standards, etc. can be used. Specifically, polysorbate (such as polysorbate 80), polyoxyethylene / polyoxypropylene copolymer, polyoxyethylene (160) polyoxypropylene (30) glycol, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester and Nonionic surfactants such as polyoxyethylene castor oil derivatives, and anionic surfactants such as sodium lauryl sulfate and sodium alkyl sulfate.

  As the flavoring agent, a flavoring agent listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Pharmaceutical Standards or the Pharmaceutical Additives Standard, and the like can be used. Specific examples include organic acid salt for taste-masking such as sodium glutamate, sodium 5'-inosinate, sodium 5-guanylate and sodium aspartate.

As the fragrance, fragrances listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Pharmaceuticals or the Standards for Pharmaceutical Additives, etc. can be used. Specific examples include fragrance lemon oil, orange oil, grapefruit oil, strawberry oil, menthol and brackish oil.

  As the sweetener, a sweetener listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Pharmaceuticals or the Standards for Pharmaceutical Additives, etc. can be used. Specific examples include sodium saccharin, dipotassium glycyrrhizin, aspartame, stevia, thaumatin, and acesulfame potassium.

  As the sour agent, a sour agent listed in the Japanese Pharmacopoeia, the Japanese Pharmacopoeia Standards for Pharmaceuticals or the Pharmaceutical Additives Standard, etc. can be used. Specific examples include citric acid, tartaric acid, malic acid, ascorbic acid and the like.

  The administration method of the composition of the present invention is not particularly limited, and the composition containing (A) dicetiamine and / or a salt thereof and component (B) aspartic acid and / or thioctic acid can be administered simultaneously or at different times. . When these components are administered at different times, it is desirable to administer other active components within a time period during which the blood concentration of the previously administered active component does not decrease. As a method for administering the medicament in the present invention, it is preferable to administer these components simultaneously from the viewpoint of fatigue prevention and / or recovery action.

  The composition of the present invention can be used as pharmaceuticals, quasi drugs, cosmetics, foods, etc., and is caused by, for example, physical fatigue such as fatigue accompanying physical load such as exercise load, or mental load such as environmental stress. However, in the present invention, it is preferably applied to physical fatigue. The composition of the present invention has an excellent prevention and / or recovery action against physical fatigue and / or mental fatigue, as shown in Examples below, and based on the fatigue prevention and / or recovery action. Alleviation of symptoms such as muscle pain, low back pain, stiff shoulders, general malaise, nourishment, nutritional supplementation (eg, physical fatigue, decreased physical fitness after illness, loss of appetite, malnutrition, febrile wasting disease, pregnancy lactation, etc.) In this case, it is possible to exert effects such as nutritional supplementation and physical strength enhancement.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, this invention is not limited to the following Example.

Test example 1
An exercise experiment was performed according to the following method.
<Test method>
Seven-week-old Slc: SD male rats were preliminarily raised for 5 days in plastic cages. After preliminary breeding, rats were placed in a plastic cage (hereinafter also referred to as a water immersion cage) in which tap water (water temperature: 23 ° C. ± 1 ° C.) was administered to the height of 1.5 cm from the bottom after the first test drug administration. Moved quickly. Thereafter, the test drug was orally administered once a day for 5 days from the first day of the test. On the sixth day of the test, a weight of 7% was attached to the ridge of the rat with a gum tape, and then a circular water tank containing tap water (diameter: 18 cm, height: 70 cm, water depth: 40 cm, water temperature 23 ± 1 ° C.) The time from the start of swimming until the nose of the rat sinks from the water surface for 10 seconds (hereinafter also referred to as swimming time) was measured.
As test substances, dicetiamine hydrochloride (hereinafter abbreviated as “DCET” in the examples) 10 mg / kg, aspartic acid (hereinafter abbreviated as “ASP” in the examples) 100 mg / kg, and DCET 10 mg / kg Using a combination of ASP 100 mg / kg (hereinafter abbreviated as “DCET + ASP” in the examples), these were suspended in 0.5% methylcellulose (hereinafter abbreviated as MC) and used for the test.

<Experimental result>
The results are shown in Table 1 and FIG.

コントロールの平均遊泳時間を１．００としたときの各試験群の平均遊泳時間を遊泳時間相対値として表した。
Ｎ＝５〜１０
＊：ｐ＜０．０５ｖｓコントロールおよびＤＣＥＴ
バルジの方法による相乗効果の判定：１．９７（ＤＣＥＴ＋ＡＳＰ）＞１．０６（ＤＣＥＴ）×１．２５（ＡＳＰ）

The average swimming time of each test group when the average swimming time of the control was 1.00 was expressed as a relative value of swimming time.
N = 5-10
*: P <0.05 vs control and DCET
Judgment of synergistic effect by bulge method: 1.97 (DCET + ASP)> 1.06 (DCET) × 1.25 (ASP)

Test example 2
<Test method>
The test was carried out in the same manner as in Test Example 1, except that the dose of DCET was 30 mg / kg, and thioctic acid amide (hereinafter abbreviated as “ALA” in the examples) was 10 mg / kg. The results are shown in Table 2 and FIG.

コントロールの平均遊泳時間を１．００としたときの各試験群の平均遊泳時間を遊泳時間相対値として表した。
Ｎ＝５〜１０
＊：ｐ＜０．０５ｖｓコントロールおよびＤＣＥＴ
バルジの方法による相乗効果の判定：２．１８（ＤＣＥＴ＋ＡＬＡ）＞１．４５（ＤＣＥＴ）×１．３３（ＡＬＡ）

The average swimming time of each test group when the average swimming time of the control was 1.00 was expressed as a relative value of swimming time.
N = 5-10
*: P <0.05 vs control and DCET
Judgment of synergistic effect by bulge method: 2.18 (DCET + ALA)> 1.45 (DCET) × 1.33 (ALA)

In comparison with the control group to which MC was administered, although a slight increase in swimming time was observed in the DCET, ASP and ALA single administration groups, it was not a significant effect. However, in the group administered with the composition of the present invention (DCET + ASP or DCET + ALA), a significant increase in swimming time was observed compared to the control group and each single administration group. The relative swimming time values were 1.06 in the DCET administration group and 1.25 in the ASP administration group in Test Example 1, and their product (1.32) was the swimming time relative value of DCET + ASP (1. 97), and in Test Example 2, it was 1.45 in the DCET administration group and 1.33 in the ALA administration group, and the product (1.92) was based on the swimming time relative value of DCET + ALA (2.18). It is concluded that the combination of (A) dicetiamine and / or its salt and component (B) aspartic acid and / or thioctic acid is synergistic with regard to fatigue prevention and / or recovery action by the bulge method. It was attached.
From the above results, the medicament of the present invention is capable of treating (A) dicetiamine and / or a salt and component thereof (B) aspartic acid and against physical fatigue caused by physical stress and mental fatigue caused by environmental stress in the aquatic environment. It has been clarified to have a synergistic fatigue prevention and / or recovery action by the combined use of thioctic acids.

＊シアノコバラミンを６０μｇ含有する。
＊＊製剤用添加物として、モノラウリン酸ソルビタン、ゼラチン、白糖、タルク、グリセリン脂肪酸エステル、乳糖水和物、結晶セルロース、ヒドロキシプロピルセルロース、カルメロースカルシウム、ステアリン酸マグネシウム、ポリビニルアルコール・アクリル酸・メタクリル酸メチル共重合体、ヒプロメロース、酸化チタン、黄色三二酸化鉄、三二酸化鉄を含有する。 Production Example 1
A composition containing the following components (daily dose, in 4 tablets) is produced.

* Contains 60 μg of cyanocobalamin.
** Pharmaceutical additives include sorbitan monolaurate, gelatin, sucrose, talc, glycerin fatty acid ester, lactose hydrate, crystalline cellulose, hydroxypropylcellulose, carmellose calcium, magnesium stearate, polyvinyl alcohol, acrylic acid, methacrylic acid Contains methyl copolymer, hypromellose, titanium oxide, yellow ferric oxide, ferric oxide.

[Example 1]
[Tablet production method]
Add the hydroxypropyl cellulose dissolved in purified water to the mixed powder of discetiamine hydrochloride hydrate, riboflavin, pyridoxine hydrochloride, d-α-tocopherol succinate, crystalline cellulose, lactose hydrate and carmellose calcium, flow Perform layer granulation. Riken dry B ₁₂ -B ₁ CN-GP, magnesium L-aspartate / potassium, crystalline cellulose, carmellose calcium and magnesium stearate are mixed with the dried and sized powder, and mixed until uniform To do. The mixture was tableted with a tableting machine to obtain an uncoated tablet (270 mg).
Film coating by spraying uncoated tablet with spray liquid containing polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, hypromellose, titanium oxide, yellow ferric oxide, ferric oxide, talc, ethanol and purified water And film coated tablets (278 mg) were obtained.

  The composition of the present invention has an extremely excellent fatigue prevention and / or recovery action due to the synergistic action of (A) dicetiamine and / or a salt thereof and component (B) aspartic acid and / or thioctic acid.

Claims (6)

The following components (A) and (B)
A composition for preventing and / or recovering from fatigue, comprising (A) dicetiamine and / or a salt thereof (B) aspartic acids and / or thioctic acids.   The composition of claim 1, wherein component (A) is dicetiamine hydrochloride.   The composition according to claim 1 or 2, wherein component (B) is L-aspartic acid and / or a salt thereof.   The composition according to claim 1 or 2, wherein component (B) is potassium L-aspartate and / or magnesium.   The composition according to any one of claims 1 to 4, wherein the thioctic acid is a thioctic acid amide.   A composition for preventing and / or recovering from fatigue, comprising discetiamine hydrochloride, potassium L-aspartate and magnesium L-aspartate.

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