KR101424833B1 - Pharmaceutical agent for prevention of fatigue and/or recovery from fatigue - Google Patents

Abstract

Providing medicaments having excellent prophylactic and / or remedial action against physical fatigue and / or mental fatigue. Adenosine 5'-triphosphate or a physiologically acceptable salt thereof, and a garlic work product, for preventing and / or recovering fatigue.

Description

[0001] PHARMACEUTICAL AGENT FOR PREPARING OF FATIGUE AND OR RECOVERY FROM FATIGUE [0002]

The present invention relates to a medicament having a preventive and / or remedial action against physical fatigue and / or mental fatigue.

Recently, there is a trend of increasing the number of people suffering from fatigue. Fatigue is defined as "a temporary condition in which functional capacity resulting from physical or mental activity is reduced" and is generally classified as physical fatigue and mental fatigue. Fatigue not only lowers the quality of life but also causes a decrease in immunity and the like, leading to unexpected diseases and the like. Therefore, it is desired to provide medicines having excellent fatigue recovery action.

Adenosine 5'-triphosphate is a compound with high-energy phosphoric acid bonds and has a property of releasing a large amount of energy when hydrolyzed with adenosine 5'-2-phosphate (ADP) and phosphoric acid. Due to such properties, adenosine 5'-triphosphate is widely involved in the metabolism of carbohydrate, fat, or protein as a phosphoric acid donor, and the energy generated by the hydrolysis reaction of adenosine 5'- It is the driving force of the energy constitutive reaction.

Regarding the use of adenosine 5'-triphosphate as a medicament, it is known that chronic gastritis, in which the regulatory function is stabilized in head trauma sequelae, heart failure, Medicines such as 40 to 60 mg once a day for three times a day or 100 mg once a day for Meniere's disease and dizziness based on inner ear disorders are administered three times a day. It is also known that medicines combining adenosine 5'-triphosphate and vitamin B ₁ derivatives have a therapeutic effect on stable fatigue (Patent Document 1). In addition, a method of reducing fatigue by administering adenosine 5'-triphosphate is known (Patent Document 2).

On the other hand, garlic processed products such as dried powder extracted from garlic have been confirmed to have a medicinal effect such as strength, dryness, suitability, and fatigue recovery. Examples of such medicines include a refinisher and a garlic work product such as oxamidine (B) a vitamin B, a nicotinic acid amide, a biotin, or a combination thereof; and (c) , Iron ammonium citrate, calcium pantothenate and caffeine, and (c) stevia, wherein the bitter component content and the stevia content in the preparation are 1 part by weight (Patent Document 4), which is characterized in that the content of stevia is in the range of 0.001 to 0.1 parts by weight with respect to the amount of stevia (Patent Document 4) (Patent Literature 5), which is characterized in that it contains, as an essential component, an embryo, a garlic dried garlic, and a crown of gold as essential components; a stable fatigue improving agent containing benofathiamine and garlic work product oxoamidine 6) are known.

However, in any of the above-mentioned known techniques, the synergistic effect on fatigue prevention and / or restorative action is exhibited by combining adenosine 5'-triphosphate or a physiologically acceptable salt thereof and garlic products, It is not.

Patent Document 1: JP-A-1-308232

Patent Document 2: Japanese Published Patent Application No. 2004-535417

Patent Document 3: JP-A-6-9417

Patent Document 4: JP-A-9-110708

Patent Document 5: JP-A-2001-114695

Patent Document 6: JP-A-2002-275071

DISCLOSURE OF INVENTION

Problems to be solved by the invention

It is an object of the present invention to provide a new medicament having a preventive and / or restorative action against physical fatigue and / or mental fatigue.

Means for solving the problem

The inventors of the present invention have conducted intensive studies in order to solve the above problems. As a result, it has been found that remarkable prevention of fatigue and / or restoration action can be confirmed by using adenosine 5'-triphosphate or a physiologically acceptable salt thereof in combination with a garlic product, And a synergistic fatigue preventing and / or restoring action can be achieved compared with the case where it is used alone. Thus, the present invention has been completed.

That is, the present invention provides a medicament for prevention and / or recovery of fatigue which is a combination of adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a garlic work product.

The present invention also provides the use of a combination of adenosine 5'-triphosphate or a physiologically acceptable salt thereof and garlic artifacts for the manufacture of a medicament for prevention and / or recovery of fatigue.

The present invention also provides a method of preventing and / or recovering fatigue characterized by administering an effective amount of adenosine 5'-triphosphate or a physiologically acceptable salt and garlic work.

Effects of the Invention

The medicament of the present invention has excellent fatigue prevention and / or restorative action due to the synergistic effect of adenosine 5'-triphosphate or a physiologically acceptable salt thereof and garlic work product, and is excellent in physical fatigue and / or mental fatigue Prevention and / or healing action.

Brief Description of the Drawings Fig. 1 is a diagram showing the swelling increase (%) in ATP 120 mg / kg, oxoamidine 50 mg / kg, and its combination administration group.

2 is a graph showing the increase (%) of swelling in the group administered with 120 mg / kg of ATP, 15 mg / kg of oxoamidine, and the group administered with the combination.

BEST MODE FOR CARRYING OUT THE INVENTION

The medicament of the present invention is a medicine for prevention and / or restoration of fatigue, which is a combination of adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a garlic work product. That is, the medicament of the present invention is a medicament for prevention and / or restoration of fatigue, wherein adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a garlic workpiece are administered simultaneously or at different times.

The medicament of the present invention is provided as a combination (kit) of a preparation in unit dosage form containing adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a preparation in unit dosage form containing a garlic work product, or Adenosine 5'-triphosphate or a physiologically acceptable salt thereof, together with a garlic artifact as a pharmaceutical composition in unit dosage form. It is more preferable to be provided as a pharmaceutical composition in unit dosage form containing adenosine 5'-triphosphate or a physiologically acceptable salt thereof together with a garlic work product.

The " adenosine 5'-triphosphate or a physiologically acceptable salt thereof " used in the medicament of the present invention is a known substance and can be easily obtained by those skilled in the art. The physiologically acceptable salts of adenosine 5'-triphosphate are not particularly limited, and examples thereof include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as magnesium salt and calcium salt. Of these, disodium adenosine 5'-triphosphate is particularly preferable from the viewpoint of fatigue prevention and / or restoration action. Since a formulation containing adenosine 5'-triphosphate or a physiologically acceptable salt thereof is already in the form of an oral dosage form or an injectable preparation, the adenosine 5'-triphosphate or a physiologically acceptable salt thereof may be used alone When the medicament of the present invention is to be provided by using the agent of the present invention, a formulation containing commercially available adenosine 5'-triphosphate or a physiologically acceptable salt thereof may be used. For example, " Adhose " (Kyowa Co., Ltd.) and the like are commercially available.

The kind of the "garlic product" used in the medicament of the present invention is not particularly limited, and any product obtained by processing lilies and garlic (Allium sativuml.) Can be used. In the present specification, the term " processing " means that any processing such as heating, drying, grinding, or extraction is performed on raw garlic, and the type of processing is not particularly limited.

The processing includes, for example, a process of drying raw garlic or a process of pulverization after drying, a process of steam distillation of raw garlic, a process of extracting raw garlic with oil, water, hot water or a water-soluble organic solvent, And the like, and in particular, a treatment for extracting with a water-soluble organic solvent is preferable. Examples of the oil used for the extraction include edible vegetable oils such as vegetable oil, olive oil and soybean oil. Examples of the water-soluble organic solvent include lower alcohols such as ethanol and isopropanol, and propylene glycol or di And glycols such as ethylene glycol.

From the viewpoint of prevention of fatigue and / or recovery action, for example, processed garlic, garlic extract, garlic extract, or dried garlic are preferable as the processed garlic products, and particularly the processed garlic is preferable. The processed garlic refers to a garlic powder or extract prepared through a process such as a lower alcohol extraction with a heat-treated garlic extract, and examples thereof include oxoamidine (trade name) (manufactured by Riken Chemical Industries Co., Ltd.), oxoamidine (Manufactured by Riken Chemical Industry Co., Ltd.), oxolezin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.), or oxolezin (registered trademark), manufactured by Riken Chemical Industry Co., Ltd., are commercially available. As garlic extract, for example, garlic extract (manufactured by Alps Chemical Industries Co., Ltd.) or garlic extract (manufactured by Nippon Powder Pharmaceutical Co., Ltd.) and the like are commercially available. As the dried garlic, for example, garlic powder (manufactured by Riken Chemical Industries Co., Ltd.) or roast garlic powder EX (manufactured by Riken Chemical Industries Co., Ltd.) and the like are commercially available. Among these garlic products, oxoamidine (trademark) (manufactured by Riken Chemical Industries Co., Ltd.), oxoamidine (trademark) horse (manufactured by Riken Chemical Industry Co., Ltd.), oxole resin (registered trademark) , Or oxolezin (registered trademark) horse (manufactured by Riken Chemical Industries Co., Ltd.) are preferable.

The combination ratio of the adenosine 5'-triphosphate or the physiologically acceptable salt thereof and the garlic work product in the medicament of the present invention is not particularly limited and may be appropriately selected by those skilled in the art by the test method specifically shown in the following Examples . In the present invention, in the case of using, for example, processed garlic as a garlic work product, 1 part by weight of adenosine 5'-triphosphate or physiologically acceptable salt thereof is added in view of the synergistic effect of fatigue prevention and / The processed garlic is used in an amount of 0.006 to 34 parts by mass, more preferably 0.012 to 17 parts by mass, further preferably 0.06 to 3.4 parts by mass, further preferably 0.1 to 2 parts by mass, particularly preferably 0.12 To 0.42 parts by mass. In addition, in the case of using other garlic workpieces, from the viewpoint of the synergistic effect of fatigue prevention and / or restoration, 1 part by weight of adenosine 5'-triphosphate or physiologically acceptable salt thereof is added to the amount of garlic Is in the range of 0.012 to 3400 parts by mass, more preferably 0.024 to 1700 parts by mass, still more preferably 0.12 to 340 parts by mass, still more preferably 0.2 to 4 parts by mass, particularly preferably 0.24 to 0.48 parts by mass It is preferable to use it in the range.

In addition to the adenosine 5'-triphosphate or physiologically acceptable salt thereof and the garlic product, the medicament for prevention and / or recovery of fatigue according to the present invention may further contain, for the purpose of enhancing fatigue prevention and / It is preferable to blend B-series. Examples of vitamin B include vitamin B _{1 such} as thiamine hydrochloride, thiamine nitrate, bistiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salt, decathiamine hydrochloride, furylthiamine hydrochloride, octothiamine, cocothiamine, bis Eve thiamine, bis Ben thiamine, greener sulfonic thiamine, Pro sulfonic thiamine, benpo thiamine etc.; vitamin B Plastic as ₂ empty adenine dinucleotide sodium, riboflavin phosphate, riboflavin sodium butyrate, riboflavin, etc.; vitamin B ₆ as pyridoxine hydrochloride, phosphate Pyridoxal, and the like; vitamin B _{12 such} as hydroxycobalamin hydrochloride, hydroxycobalamin acetate, cyanocobalamin, hydroxocobalamin, and meccobalamin.

In the present invention, it is preferable to blend at least one kind of vitamin B selected from the group consisting of vitamin B ₁ , vitamin B ₂ , vitamin B ₆ and vitamin B ₁₂ in view of the synergistic effect of fatigue prevention and / B _1, 3 that vitamin B _2, vitamin B _6, and is more preferable to compound a vitamin B two or more kinds selected from vitamin B _12, and selected from vitamin B _1, vitamin B _2, vitamin B ₆ and vitamin B ₁₂ It is more preferable to blend more than two kinds of vitamin B species, and it is particularly preferable to blend a combination of vitamin B ₁ , vitamin B ₂ , vitamin B ₆ and vitamin B ₁₂ .

The combination ratio of adenosine 5'-triphosphate or a physiologically acceptable salt thereof and vitamin B in the medicament of the present invention is not particularly limited. From the viewpoint of the synergistic effect of fatigue prevention and / or restoration, , 0.0003 to 20 parts by mass of vitamin B ₁ , 0.0005 to 8 parts by mass of vitamin B ₂ , and 0.001 to 20 parts by mass of vitamin B ₆ relative to ₁ part by mass of adenosine 5'-triphosphate or physiologically acceptable salt thereof , and vitamin B ₁₂ the range of 0.0000003 - 0.3 mass parts, preferably vitamin B ₁ of 0.003 to 2 mass parts, 0.005 ~ 0.8 parts by weight, 0.01 to 2 parts by weight of a vitamin B ₆ vitamin B _2, and vitamin B ₁₂ Is preferably used in a range of 0.000003 to 0.03 part by mass.

The medicament of the present invention may be either a medicament suitable for oral administration or a medicament suitable for parenteral administration. Preferably a medicament suitable for oral administration.

It is also preferred that the medicament suitable for oral administration is provided as a solid, semi-solid or liquid pharmaceutical composition containing adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a garlic processed product in one unit dosage form desirable.

When the medicament of the present invention is provided as a medicament suitable for oral administration or as a medicament suitable for parenteral administration, the dosage form thereof is not particularly limited. For example, a solid pharmaceutical composition such as a powder or granules, a tablet, a tablet, a film-coated tablet, a sugar-coated tablet, a soft capsule or a hard capsule, a medicinal composition in the form of a solution such as a drink or a semi-solid Of the present invention. In the present invention, it is particularly preferable to use a solid pharmaceutical composition in view of stability and ease of administration.

When the medicament of the present invention is provided as a medicinal composition containing adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a garlic work product, the compounding amount of each component in the medicinal composition is not particularly limited, After considering the combination ratio, depending on the form of the pharmaceutical composition. For example, in the case of providing a pharmaceutical composition in solid form, when using processed garlic as a garlic work, 1 to 300 mg of adenosine 5'-triphosphate or physiologically acceptable salt thereof per 1 unit of the pharmaceutical composition , And 1 to 300 mg of processed garlic may be blended. In addition to the adenosine 5'-triphosphate or a physiologically acceptable salt thereof and the garlic processed product, in the case of additionally adding the vitamin B class, for example, about 0.3 to 100 mg of vitamin B ₁ per unit, the vitamin B _{2 of} about 0.5 to about 50 mg, about 1 to about 100 mg of vitamin B ₆ , and about 0.0003 to about 1.5 mg of vitamin B ₁₂ .

The medicament for prevention and / or restoration of fatigue according to the present invention includes adenosine 5'-triphosphate or a physiologically acceptable salt thereof, garlic work product, vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ Can be appropriately compounded according to the purpose of the compounding. Examples of such components include vitamin A, water-soluble vitamins, vitamin D, vitamin E, vitamin-like substances, minerals, caffeine, amino acids, hepatic insecticides, herbal medicines and other ingredients.

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

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

Examples of the vitamin D include ergocalciferol and cholecalciferol.

Examples of vitamin E include succinic acid d-α-tocopherol, succinate dl-α-tocopherol, dl-α-tocopherol succinate d-α-tocopherol acetate, dl-α-tocopherol, d- And the like.

Examples of vitamin-like substances include inositol, inositol hexanicotinate, aurotic acid, choline aurotate, gamma oliginol, thioctanoic acid, thioctanoic acid amide, carnitine chloride, ubidecarenone, choline tartrate and rutin .

Examples of the 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 and sodium chondroitin sulfate.

Caffeine includes caffeine derivatives such as anhydrous caffeine and sodium benzoate caffeine.

Examples of the amino acids include L-aspartic acid, potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, L-cysteine hydrochloride, L-cysteine, aminoacetic acid, L- isoleucine, arginine hydrochloride, Glutamic acid, L-threonine, L-valine, L-histidine hydrochloride, L-leucine, DL-methionine, L-phenylalanine and L-tryptophan.

Examples of the hepatic inhibiting agent include uricosteroid cichoric acid, dehydrocholic acid, glucuronolactone, glucuronic acid, glucuronic acid amide, glycyrrhizic acid, sodium glycyrrhizinate, aminoethylsulfonic acid, diisopropyl dichloroacetate Amine, methylmethionine sulfonium chloride, hepatic hydrolyzate, yoke lecithin, and the like.

There are many kinds of herbal medicines such as ginseng, fennel, gooseberry, hwanggi, hwangjeong, guarana, licorice, gugija, cinnamon, red ginseng, saffron, Carrageenan, left ear, mulifera, flax, camellia, raw, noodle, yonghan, royal jelly, and antler.

Other components include placenta and the like.

The medicament in the present invention can be suitably prepared by a technique commonly used in the art. In this case, if necessary, one or two or more kinds of additives for formulation used in the art may be used. Examples of additives for formulation include, but are not limited to, excipients, binders, disintegrators, lubricants, colorants, mating agents, and coatings.

Examples of excipients include lactose, starch, crystalline cellulose, sucrose, mannitol, and light anhydrous silicic acid. Examples of the binding agent include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, alpha starch, polyvinylpyrrolidone, polyvinyl alcohol, and pullulan. Examples of the disintegrating agent include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, and low-substituted hydroxypropyl cellulose. Examples of the lubricant include magnesium stearate or talc. Examples of the colorant include tar pigments and ferric iron dioxide. Mating agents include stevia, aspartame, or fragrance. Examples of the coating agent include film-forming polymers such as carboxymethylethylcellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic copolymer LD, hydroxypropylmethylcellulose phthalate and hydroxypropylmethylcellulose acetate succinate Can be used. When the film is formed, powders such as a plasticizer such as triethyl citrate, triacetin and polyethylene glycol, talc, titanium oxide, yellow 3 iron dioxide, 3 iron dioxide, a legal pigment, light anhydrous silicic acid, It is possible.

The dose of the medicament of the present invention is not particularly limited and may be appropriately selected according to various conditions such as the form of the medicament, the degree of symptoms to be applied, or the age of the patient. In general, adenosine 5'-triphosphate or a physiologically acceptable salt thereof may be administered to an adult in an amount of about 6 to about 3000 mg / day, more preferably about 20 to 300 mg / day. Depending on the dose, Depending on the ratio described, the dose of garlic and vitamin B can be determined.

The method of administering the medicament of the present invention is not particularly limited, and adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a garlic workpiece can be administered simultaneously or at different times. When these components are administered at different times, it is preferable to administer other effective components within a time period in which the concentration of the effective component administered first is not lowered. As the administration method of the medicament in the present invention, it is preferable to administer these components at the same time from the viewpoint of fatigue prevention and / or recovery action.

The medicament of the present invention is applicable to any physical fatigue such as fatigue accompanied by physical load such as exercise load, or mental fatigue (central fatigue) such as fatigue caused by mental load such as environmental stress or chronic fatigue syndrome In the present invention, it is preferable to apply to physical fatigue. The medicament of the present invention has an excellent preventive and / or restorative action against physical fatigue and / or mental fatigue as shown in the later examples, and has a stable fatigue, muscular pain, back pain (For example, physical fatigue, poor physical fitness, poor appetite, malnutrition, fever, exhaustion, pregnancy and lactation) in the case of allergic diseases, alleviation of all symptoms such as shoulder stiffness and general boredom, , Etc.), physical strength, and the like.

Hereinafter, the present invention will be described more specifically by way of examples, but the present invention is not limited to the following examples.

Test Example 1

The exercise load test was carried out according to the following method.

<Test Method>

A 5-week-old BALB / C male mouse was placed in a 20 cm-diameter water tank kept at 22 캜 on the first day of the test, and the amount of exercise (pre value) for 5 minutes was measured. The amount of swimming was expressed as the number of movements to the adjacent and diagonal areas when the water surface of the water tank was divided into four. Thereafter, the test drug was repeatedly administered for 4 days from the first day of the test and fasted overnight on the fourth day of the test. On the fifth day of the test, the mice were kept in the same water bath for 20 minutes, and the test drug was orally administered after termination of swimming. Thereafter, after leaving for 30 minutes, a postal value of 5 minutes was measured in the same water bath to calculate a rate of change in swimming rate ((post value / pre value) × 100). Further, an increase in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of change in the rate of survival to the control (0.5% Average rate of change in swimming distance).

120 mg / kg of adenosine 5'-triphosphate (hereinafter abbreviated as "ATP" in the examples), 50 mg / kg of oxoamidines (manufactured by Riken Chemical Industries Co., Ltd.), 120 mg / kg of ATP (Hereinafter abbreviated as &quot; ATP + oxoamidines &quot; in the following examples) were used to suspend or dissolve them in 0.5% methylcellulose and to give them to the test.

<Experimental Results>

The results are shown in Fig. 1 and Table 1.

Test group Dose
(mg / kg) Rate of change of swimming distance (%)
Mean ± SE Relative value of swimming amount
Growth Rate (%)
Mean ± SE control - 44.8 ± 3.6 1.00 - ATP 120 49.4 ± 5.5 1.10 4.6 ± 5.5 Oxoamidine 50 51.2 ± 5.4 1.14 6.4 ± 5.4 ATP + oxoamidines 120 + 50 62.3 ± 4.4 * 1.39 17.5 + 4.4

And the rate of change of the average swimming amount of each test group when the rate of change of the average swimming amount of the control was set to 1.00 was expressed as the swimming amount relative value.

The increase in the rate of change in the rate of change in the amount of exercise relative to the control of the drug-administered group was expressed as the increase in the amount of swimming.

N = 14-17

*: P <0.05 vs control (Dunnett type multiple comparison)

Determination of synergistic effect by the method of bulging: 1.39 (ATP + oxoamidine) &gt; 1.10 (ATP) x 1.14 (oxoamidine)

Test Example 2

<Test Method>

ATP was administered in an amount of 120 mg / kg, and the dosage of oxoamidine was adjusted to 15 mg / kg. The results are shown in FIG. 2 and Table 2.

Test group Dose
(mg / kg) Rate of change of swimming distance (%)
Mean ± SE Relative value of swimming amount
Growth Rate (%)
Mean ± SE control - 45.3 ± 4.8 1.00 - ATP 120 47.7 ± 10.4 1.05 2.4 ± 10.4 Oxoamidine 15 47.7 ± 5.8 1.05 2.4 ± 5.8 ATP + oxoamidines 120 + 15 67.5 ± 14.4 1.49 22.2 ± 14.4

The rate of change of the average swimming distance of each test group when the average rate of change of the swimming distance of the control was set to 1.00 was expressed as the swimming distance relative value.

The increase in the rate of change in the rate of change in the amount of exercise relative to the control of the drug-administered group was expressed as the increase in the amount of swimming.

N = 7

Determination of synergistic effect by the method of bulging: 1.49 (ATP + oxoamidine) &gt; 1.05 (ATP) x 1.05 (oxoamidine)

In comparison with the control group to which MC was administered, although a slight increase in the rate of change in swimming rate was observed in the case of administration of ATP or oxoamidane alone, it was not remarkable. However, in the administration group (ATP + oxoamidine) of the medicament of the present invention, a remarkable increase in the rate of change of the swimming rate was observed, and a remarkable difference was confirmed in comparison with the control group to which MC was administered. The ratio of the rate of increase of the rate of change of the rate of change of the rate of exercise to control (the relative value of the amount of swimming) was 1.10 in the ATP administration group and 1.14 in the oxoamidane administration group in Test Example 1 and their product (1.25) (1.10) of ATP + oxoamidine was smaller than 1.49 of ATP + oxoamidine and 1.05 of ATP + oxoamidane group in Test Example 2 and 1.05 of ATP + It has been concluded that the combination of the triphosphate or physiologically acceptable salt thereof and the garlic artifact exerts a synergistic effect on fatigue prevention and / or restorative action. It was also confirmed that the rate of change in the amount of swimming movement was more increased in the group of administration of the medicament of the present invention than in the group of administration of ATP or oxoamidine alone. From the above results, it can be concluded that the medicament of the present invention is useful for mental fatigue caused by physical fatigue accompanied by exercise loads and environmental stress in an underwater environment, adenosine 5'-triphosphate or a physiologically acceptable salt thereof and garlic It has become apparent that they have a synergistic fatigue prevention and / or recovery action by the combined use of the workpiece.

Production Example 1

1 day (3 tablets) during

Adenosine 5'-triphosphate 60.0 mg

Oxoamidine 50.0 mg

12.0 mg of dried extract (converted to crude drug) 300 mg)

30.0 mg of Hwanggi-old dried extract (converted to crude drug) (240 mg)

Arginine hydrochloride 50.0 mg

Thiamine nitrate 10.0 mg

Riboflavin 4.0 mg

Pyridoxine hydrochloride 10.0 mg

Calcium succinate dl -? - tocopherol 20.7 mg

Sodium ascorbate 112.6 mg

Nicotinic acid amide 25.0 mg

Anhydrous caffeine 50.0㎎

40.0㎎ of hardened oil

Hydroxypropylcellulose 24.0 mg

Crystalline cellulose 125.7 mg

Carmeloose 30.0 mg

Magnesium stearate 6.0 mg

Total 660.0㎎

480 g of adenosine 5'-triphosphate, 400 g of oxoamidane, 96 g of dried persimmon extract, 240 g of dried hull extract, 400 g of arginine hydrochloride, 80 g of thiamine nitrate, 32 g of riboflavin, 80 g of pyridoxine hydrochloride, 165.6 g of dl- (FAURK: FM-VG-25 type) was charged with 900 g of sodium ascorbate, 200 g of nicotinic acid amide, 400 g of anhydrous caffeine, 320 g of hardening oil, 192 g of hydroxypropylcellulose, 1005.6 g of crystalline cellulose and 240 g of Carmelose After mixing, 600 g of ethanol was added and combined. This association was dried using a fluid bed drier (NFLO-5 type, manufactured by Freight Industries), and then dried using a sizing machine (Okada hole: ND-10S type). 5232 g of this sizing product and 48 g of magnesium stearate were charged into a mixer (Kotobuki Kogyo Kogyo KK: PM-50), mixed and then charged into a tableting machine equipped with a ball having a diameter of 8 mm and a radius of curvature of 10 mm ) To obtain 220 mg of tablets per tablet.

Production Example 2

1 day (3 tablets) during

Adenosine 5'-triphosphate 120.0 mg

Oxoamidine 50.0 mg

Benzothiamine 138.3 mg

Riboflavin 12.0㎎

Pyridoxine hydrochloride 50.0 mg

60.0 g of cyanocobalamin

Gamma Oligonol 10.0 mg

103.6 mg of dl-α-tocopherol calcium succinate

D-mannitol 116.0 mg

Crystalline cellulose 120.1 mg

37.5 mg of hydroxypropyl cellulose

Carmelose calcium 45.0 mg

7.5 mg magnesium stearate

Total 810.0㎎

620 g of d-mannitol, 696 g of D-mannitol, 720 g of D-mannitol, 720 g of adenosine 5'-triphosphate, 300 g of oxoamidane, 829.8 g of benfotiamine, 72 g of riboflavin, 300 g of pyridoxine hydrochloride, 225 g of hydroxypropylcellulose and 270 g of carmellose calcium were put into a high-speed agitation granulator (Paureck: FM-VG-25 type) and mixed. Then, 500 g of ethanol in which 360 mg of cyanocobalamin had been dissolved was added thereto, And then crushed and assembled using a sizing machine (Okada hole: ND-10S type). The granules were dried using a fluid bed dryer (Freund Industries, NFLO-5 type), and then dried using a sizing machine (Okada hole: ND-10S type). 4815 g of this sizing product and 45 g of magnesium stearate were placed in a mixer (Asahi Kogyo: B2 / 109 type) and mixed. Thereafter, a tablet machine (HTA-AP18SS type) equipped with a ball having a diameter of 8.5 mm and a radius of curvature of 12 mm was used One tablet of 270 mg of tablets was obtained.

Production Example 3

1 day (6 tablets) during

Adenosine 5'-triphosphate 60.0 mg

Oxoamidine 30.0 mg

20.0 mg of furylsulfiamine hydrochloride

Sodium chondroitin sulfate 900.0 mg

D-mannitol 125.0 mg

Crystalline cellulose 130.0 mg

40.8 mg of hydroxypropylcellulose

Carmelose calcium 61.2 mg

Magnesium stearate 13.0 mg

Total 1380.0㎎

250 g of D-mannitol, 520 g of crystalline cellulose, 163.2 g of hydroxypropylcellulose, and 244.8 g of carmellose calcium were stirred at a high speed (FM-VG-25 type). After mixing, 900 g of ethanol was added and combined, and the resulting mixture was ground and assembled by using a sizing machine (Okada hole: ND-10S type). The granules were dried using a fluid bed dryer (Freund Industries, NFLO-5 type), and then dried using a sizing machine (Okada hole: ND-10S type). 5388 g of this sizing product and 52 g of magnesium stearate were placed in a mixer (Asahi Kogyo: B2 / 109 type) and mixed. Thereafter, a tablet machine (HTA-AP18SS type) equipped with a ball having a diameter of 8 mm and a radius of curvature of 12 mm was used One tablet of 230 mg tablets was obtained.

Production Example 4

1 day (3 tablets) during

Adenosine 5'-triphosphate 60.0 mg

Oxoamidine 20.0 mg

Carrot extract (600mg of raw herb medicine) 180.0mg

Acetic acid d-a-tocopherol 10.0 mg

Bisbenthiamine 20.0 mg

Riboflavin 10.0 mg

Pyridoxine hydrochloride 20.0 mg

20.0 g of cyanocobalamin

Calcium pantothenate 20.0 mg

Nicotinic acid amide 20.0 mg

Hardened oil 36.0㎎

Crystalline cellulose 144.0 mg

Hydroxypropylcellulose 24.0 mg

Carmellose calcium 30.0 mg

Magnesium stearate 6.0 mg

Total 600.0㎎

480 g of adenosine 5'-triphosphate, 160 g of oxoamidane, 1440 g of carrot extract, 80 g of d-? -Tocopherol acetate, 160 g of bisbenthiamine, 80 g of riboflavin, 160 g of pyridoxine hydrochloride, 160 g of calcium pantothenate, 160 g of nicotinic acid amide, 700 g of ethanol in which 160 mg of cyanocobalamin had been dissolved was added to a high-speed agitation granulator (Paureck: FM-VG-25 type) and mixed with 1152 g of crystalline cellulose, 192 g of hydroxypropyl cellulose and 240 g of Carmelose calcium. , And further subjected to crushing assembly using a sizing machine (Okada hole: ND-10S type). The granules were dried using a fluid bed dryer (Freund Industries, NFLO-5 type), and then dried using a sizing machine (Okada hole: ND-10S type). 4752 g of this sizing product and 48 g of magnesium stearate were added to a mixer (Kotobuki Kogyo Kogyo Kogyo KK: PM-50) and mixed. After that, a tablet machine with a diameter of 8 mm, a radius of 12 mm and a radius of 4 mm -AP18SS type) to obtain tablets of 200 mg per tablet.

Production Example 5

1 day (3 tablets) during

Adenosine 5'-triphosphate 60.0 mg

Oxoamidine 30.0 mg

100.0 mg of furylsulfiamine hydrochloride

Pyridoxine hydrochloride 100.0 mg

1500 g of mecobalamin

100.0 mg of d-alpha-tocopherol acetate

Hardened oil 36.0㎎

Crystalline cellulose 112.5 mg

Hydroxypropylcellulose 24.0 mg

Carmellose calcium 30.0 mg

Magnesium stearate 6.0 mg

Methacrylic acid copolymer LD 41.0 mg

Talc 12.3mg

6.16 mg of triethyl citrate

0.54 mg of titanium oxide

Total 660.0㎎

480 g of adenosine 5'-triphosphate, 240 g of oxoamidine, 800 g of furylthiamine hydrochloride, 800 g of pyridoxine hydrochloride, 800 g of d-? -Tocopherol acetate, 288 g of hydrogenated oil, 900 g of crystalline cellulose, 192 g of hydroxypropylcellulose (MF-VG-25 type), and then 700 g of ethanol dissolved with 12 g of meso-carbamyl dissolved therein was added to the mixture, and further a sizing machine (Okada hole: ND-10S type) . The granules were dried using a fluid bed dryer (Freund Industries, NFLO-5 type), and then dried using a sizing machine (Okada hole: ND-10S type). 4752 g of this sizing product and 48 g of magnesium stearate were added to a mixer (Kotobuki Kogyo Kogyo Kogyo KK: PM-50) and mixed. After that, a tablet machine with a diameter of 8 mm, a radius of 12 mm and a radius of 4 mm -AP18SS type) to obtain 200 mg of a predetermined (uncoated) tablet.

A film coating solution prepared by dissolving and dispersing 2400 g of purified water, 410 g of methacrylic acid copolymer LD, 123 g of talc, 61.6 g of triethyl citrate, and 5.4 g of titanium oxide was sprayed on the surface of the film using an airborne type coating machine (Dowa Coater DRC-650DS type Purek Co., Ltd.) To obtain a film-coated tablet having 220 mg of one tablet.

Production Example 6

1 day (3 tablets) during

Adenosine 5'-triphosphate 60.0 mg

Oxoamidine 20.0 mg

Gugija Extract 60.0㎎

Tozan Extract 3.0 ㎎

Royal jelly 50.0㎎

Dihydrocholic acid 10.0 mg

Riboflavin 10.0 mg

2.0 g of cyanocobalamin

Acetic acid d-a-tocopherol 10.0 mg

Nicotinic acid amide

Anhydrous caffeine 50.0㎎

Hardened oil 36.0㎎

D-mannitol 93.0 mg

Crystalline cellulose 120.0 mg

Hydroxypropylcellulose 24.0 mg

Carmeloose 36.0 mg

Magnesium stearate 6.0 mg

Total 600.0㎎

4 g of adenosine 5'-triphosphate, 160 g of oxoamidane, 480 g of Goujie extract, 24 g of Tosan extract, 400 g of royal jelly, 80 g of dihydrocholic acid, 80 g of riboflavin, 80 g of acetic acid d-α-tocopherol, 96 g of nicotinic acid amide, , 288 g of hardening oil, 744 g of D-mannitol, 960 g of crystalline cellulose, 192 g of hydroxypropylcellulose and 288 g of Carmelose were put into a high-speed agitator granulator (Paureck: FM-VG-25 type) and mixed with 12 mg of cyanocobalamin And 600 g of ethanol was added thereto. This association was dried using a fluid bed drier (NFLO-5 type, manufactured by Freight Industries), and then dried using a sizing machine (Okada hole: ND-10S type). 4752 g of this sizing product and 48 g of magnesium stearate were put into a mixer (Kotobuki Kogyo Kogyo KK: PM-50) and mixed. After the mixing, a tablet machine (Hata Iron Works: HT-AP18SS type) having a diameter of 8 mm and a radius of curvature of 12 mm ) To obtain 200 mg of tablets per tablet.

Production Example 7

1 day (6 tablets) during

Adenosine 5'-triphosphate 60.0 mg

Oxoamidine 200.0 mg

Placenta extract 800.0㎎

Thiamine nitrate 10.0 mg

Acetic acid d-a-tocopherol 10.0 mg

Carrot extract 60.0㎎

Hardened oil 64.0㎎

D-mannitol 120.0 mg

Crystalline cellulose 155.0 mg

Calcium silicate 48.0 mg

Hydroxypropylcellulose 60.0 mg

Carmeloose calcium 84.0 mg

Magnesium stearate 9.0 mg

Total 1680.0㎎

180 g of adenosine 5'-triphosphate, 180 g of oxoamidine, 600 g of placenta extract, 30 g of thiamine nitrate, 30 g of d-? -Tocopherol acetate, 180 g of carrot extract, 192 g of hardening oil, 360 g of D- mannitol, 465 g of crystalline cellulose, 144 g of calcium silicate (PAUREK: FM-VG-25 type), 700 g of ethanol was added thereto, and the mixture was further mixed with a sizing machine (Okada Hole: ND -10S type). The granules were dried using a fluid bed dryer (Freund Industries, NFLO-5 type), and then dried using a sizing machine (Okada hole: ND-10S type). (HT-AP18SS type) equipped with a ball having a diameter of 9 mm and a radius of curvature of 15.5 mm was put into a mixer (Asahi Industry: B2 / 109 type) by mixing 4815 g of this sizing product and 27 g of magnesium stearate. One tablet (280 mg) was obtained.

Production Example 8

1 day (2 tablets) during

Adenosine 5'-triphosphate 120.0 mg

Oxoamidine 50.0 mg

Thiamine nitrate 30.0 mg

Riboflavin 4.0 mg

Pyridoxine hydrochloride 24.0 mg

60.0 g of cyanocobalamin

Hardened oil 24.0㎎

Crystalline cellulose 100.0 mg

20.0 mg of hydroxypropylcellulose

Carmeloose calcium 24.0 mg

Magnesium stearate 4.0 mg

Total 400.0㎎

, 288 g of pyrodicin hydrochloride, 288 g of hydrogenated oil, 1200 g of crystalline cellulose, 240 g of hydroxypropylcellulose and 288 g of carmellose calcium were placed in a high-speed agitation granulator Rem: FM-VG-25 type), and after mixing, 600 g of ethanol in which 720 mg of cyanocobalamin had been previously dissolved was added and combined. This alliance was dried using a fluid bed drier (NFLO-5 type, manufactured by Freight Industries), and then dried using a sizing machine (Okada Hole: ND-10S type). 4752 g of this sizing product and 48 g of magnesium stearate were placed in a mixer (Kotobuki Kogyo Kogyo KK: PM-50) and mixed. After mixing, a tablet machine (Hatta Iron Works: HT-AP18SS type) having a diameter of 8 mm and a radius of curvature of 14 mm ) To obtain 200 mg of tablets per tablet.

Production Example 9

1 day (3 tablets) during

Adenosine 5'-triphosphate 60.0 mg

Oxoamidine 50.0 mg

Arginine hydrochloride 50.0 mg

Gamma Oligonol 10.0 mg

Thiamine nitrate 10.0 mg

Riboflavin 4.0 mg

Pyridoxine hydrochloride 10.0 mg

Calcium succinate dl -? - tocopherol 20.7 mg

Palmitoate retinol 2000.0 IU

Sodium ascorbate 112.6 mg

Nicotinic acid amide 25.0 mg

Anhydrous caffeine 50.0㎎

100.9㎎ of hydrogenated oil

Crystalline cellulose 165.6 mg

37.5 mg of hydroxypropyl cellulose

Carmelose calcium 65.0 mg

7.5 mg magnesium stearate

Total 780.0㎎

360 g of adenosine 5'-triphosphate, 360 g of oxoamidane, 300 g of arginine hydrochloride, 60 g of gamma oligonol, 60 g of thiamine nitrate, 24 g of riboflavin, 60 g of pyridoxine hydrochloride, 124.2 g of calcium dl -? - tocopherol, 675.6 g of sodium ascorbate (PAULEK: FM-VG-25 type) was charged with 300 g of anhydrous caffeine, 605.4 g of hydrogenated oil, 993.6 g of crystalline cellulose, 225 g of hydroxypropyl cellulose and 390 g of Carmelose calcium, And 600 g of ethanol in which 7.2 g of retinol palmitate was dispersed were added and combined, and further, disintegrated using a sizing machine (Okada hole: ND-10S type). The granules were dried using a fluid bed dryer (Freund Industries, NFLO-5 type), and then dried using a sizing machine (Okada hole: ND-10S type). 4635 g of this sizing product and 45 g of magnesium stearate were placed in a mixer (Asahi Kogyo: B2 / 109 type) and mixed. The resultant was mixed with a tablet machine (HTA-AP18SS type) equipped with a ball having a diameter of 9 mm and a radius of curvature of 12 mm One tablet of 260 mg of tablets was obtained.

Claims (18)

Adenosine 5'-triphosphate or a physiologically acceptable salt thereof, and a garlic workpiece in combination. The method according to claim 1, Wherein the medicament is in the form of a pharmaceutical composition containing adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a garlic work product. 3. The method according to claim 1 or 2, Further, a medicament containing at least one kind of vitamin B selected from the group consisting of vitamin B ₁ , vitamin B ₂ , vitamin B ₆ and vitamin B ₁₂ . 3. The method according to claim 1 or 2, Medicines where fatigue is physical fatigue and / or mental fatigue. 3. The method according to claim 1 or 2, The medicinal product in which garlic is processed garlic. 3. The method according to claim 1 or 2, The combination ratio of adenosine 5'-triphosphate or a physiologically acceptable salt thereof and garlic artifact is in the range of from 0.1 to 2 g / l of garlic artifact with respect to 1 part by weight of adenosine 5'-triphosphate or physiologically acceptable salt thereof as processed garlic Mass disclaimer medication. delete delete delete delete delete delete delete delete delete delete delete delete

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