JP5114399B2 - Drugs for fatigue prevention and / or recovery - Google Patents

Description

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

  In recent years, the population suffering from fatigue has been increasing. Fatigue is defined as "temporary state of reduced functional ability resulting from physical or mental activity" and is generally classified as physical fatigue and mental fatigue. Fatigue not only lowers QOL, but also causes a decline in immunity and may lead to unexpected diseases and the like, and there is a long-awaited provision of a medicine having an excellent fatigue recovery action.

  Adenosine 5′-triphosphate is a compound having a high-energy phosphate bond, and has the property of releasing a large amount of energy when hydrolyzed to adenosine 5′-diphosphate (ADP) and phosphoric acid. Yes. Because of these properties, adenosine 5′-triphosphate is widely involved in metabolism of carbohydrates, fats, proteins, etc. as a phosphate donor, and energy generated by the hydrolysis reaction of adenosine 5′-triphosphate. Has been a driving force for energy demanding reactions in living bodies.

Regarding the use of adenosine 5'-triphosphate as a medicine, enteric tablets or granules for chronic gastritis in which sequelae of head trauma, heart failure, stabilization of regulation of eye strain and gastrointestinal dysfunction are observed. As a pharmacological therapy, 40 to 60 mg is orally administered 3 times a day, or 100 mg is administered 3 times a day for vertigo based on Meniere's disease and inner ear disorders. The pharmaceutical which combines adenosine 5'-triphosphate and the vitamin B ₁ derivatives are known to have a therapeutic effect on asthenopia (Patent Document 1). Furthermore, a method for reducing muscle fatigue by administration of adenosine 5′-triphosphate is known (Patent Document 2).

  On the other hand, garlic processed products such as dry powder extracted from garlic have been confirmed to have medicinal effects such as tonicity, healthy stomach, bowel management, and fatigue recovery, such as oxoamidin, which is an aspirating agent and garlic processed product. A liquid preparation for internal use characterized in that it contains a nourishing tonic (Patent Document 3); (a) one or more nourishing tonic crude drugs such as oxoamidin which is a processed garlic product (b) vitamin B, nicotine A formulation comprising one or more components selected from the group consisting of acid amide, biotin, ammonium iron citrate, calcium pantothenate and caffeine and (c) stevia, wherein the bitter component content and stevia in the formulation The ratio of stevia to 0.001 part by weight to 0.1 part by weight of stevia with respect to 1 part by weight of bitter component content Formulation (Patent Document 4): Nourishing tonic characterized by containing black sesame, black soybeans, kelp, green tea, dried shiitake mushrooms, rice germ, dried garlic which is a processed garlic, and Kidachi aloe (Patent Document) 5); Eye fatigue improving agent containing benfotiamine and oxoamidin which is a processed product of garlic (Patent Document 6) is known.

However, in any of the above-described known techniques, a synergistic effect on fatigue prevention and / or recovery is achieved by combining adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic product. Is not suggested or taught.
JP-A-1-308232 JP-T-2004-535417 JP-A-6-9417 JP-A-9-110708 JP 2001-114695 A JP 2002-275071 A

  An object of the present invention is to provide a new medicine having a preventive and / or recovery action against physical fatigue and / or mental fatigue.

  As a result of intensive studies to solve the above problems, the present inventors have surprisingly become prominent by combining adenosine 5′-triphosphate or a physiologically acceptable salt thereof with a processed garlic product. The present inventors have found that a fatigue prevention and / or recovery action is recognized, and that a synergistic fatigue prevention and / or recovery action can be achieved as compared with the case where they are used alone, thereby completing the present invention.

That is, the present invention provides a medicament for preventing and / or recovering from fatigue comprising a combination of adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic product.
The present invention also provides the use of a combination of adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a garlic product for the manufacture of a medicament for fatigue prevention and / or recovery. Is.
Furthermore, the present invention provides a method for preventing and / or recovering from fatigue characterized by administering an effective amount of adenosine 5′-triphosphate or a physiologically acceptable salt and processed garlic.

  The medicament of the present invention has an extremely excellent fatigue prevention and / or recovery action due to a synergistic effect of adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic product. An excellent preventive and / or recovery action against mental fatigue can be exhibited.

It is a figure which shows the amount of swimming increase (%) in ATP120mg / kg, oxoamidin powder 50mg / kg, and the combination administration group. It is a figure which shows the amount of swimming increase (%) in ATP120mg / kg, oxoamidin powder 15mg / kg, and its combination administration group.

  The medicament of the present invention is a medicament for preventing and / or recovering from fatigue, and is a combination of adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a processed garlic product. That is, the medicament of the present invention is a medicament for preventing and / or relieving fatigue, and adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic are changed simultaneously or at different times. To be administered.

  The medicament of the present invention is provided as a combination (kit) of a unit dosage form preparation containing adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a unit dosage form preparation containing processed garlic. Or a pharmaceutical composition in unit dosage form comprising adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a garlic product together. More preferably, it is provided as a pharmaceutical composition in unit dosage form comprising adenosine 5'-triphosphate or a physiologically acceptable salt thereof together with a garlic product.

  “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 kind of physiologically acceptable salt of adenosine 5′-triphosphate is not particularly limited, and examples thereof include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt and calcium salt. It is done. Of these, adenosine 5'-triphosphate disodium is particularly preferable from the viewpoint of fatigue prevention and / or recovery action. Since preparations containing adenosine 5′-triphosphate or physiologically acceptable salts thereof are already marketed as oral dosage forms or injections, adenosine 5′-triphosphate or physiologically acceptable When the pharmaceutical of the present invention is provided using a preparation containing the salt alone, a preparation containing a commercially available adenosine 5′-triphosphate or a physiologically acceptable salt thereof may be used. For example, “Adefos” (Kowa Co., Ltd.) is commercially available.

  The kind of the “processed garlic” used in the medicament of the present invention is not particularly limited, and any garlic can be used as long as it is obtained by processing bulbs of Allium sativml. In the present specification, the term “processing” means that raw garlic is subjected to some processing such as heating, drying, pulverization, or extraction, but the type of processing is not particularly limited.

  Processing includes, for example, a process of drying raw garlic or powdering after drying, a process of steam distillation of raw garlic, a process of extracting raw garlic with oil, water, hot water, a water-soluble organic solvent, or the like, or A process of heating raw garlic is included, and a process of extracting with a water-soluble organic solvent is particularly preferable. Examples of oils used for extraction include edible vegetable oils such as rapeseed oil, olive oil, and soybean oil. Examples of water-soluble organic solvents include lower alcohols such as ethanol or isopropanol; or glycols such as propylene glycol or diethylene glycol. Is mentioned.

  As the processed garlic, for example, processed potato, garlic extract, garlic extract, or dried garlic are preferable, and processed potato is particularly preferable from the viewpoint of fatigue prevention and / or recovery action. Processed daikon means garlic powder or extract prepared by subjecting a heat-treated garlic extract to a lower alcohol extraction or the like. For example, oxoamidin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.), oxoamidin (registered) Trademark) powder (manufactured by Riken Chemical Industry Co., Ltd.), oxoresin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.), or oxoresin (registered trademark) powder (manufactured by Riken Chemical Industry Co., Ltd.) are commercially available. As the garlic extract, for example, garlic extract (manufactured by Alps Pharmaceutical Co., Ltd.) or garlic extract (manufactured by Nippon Powder Chemical Co., Ltd.) is commercially available. As dried garlic, for example, garlic powder (manufactured by Riken Chemical Industry Co., Ltd.) or roasted garlic powder EX (manufactured by Riken Chemical Industry Co., Ltd.) is commercially available. Among these garlic processed products, oxoamidin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.), oxoamidin (registered trademark) powder (manufactured by Riken Chemical Industry Co., Ltd.), oxoresin (registered trademark) (manufactured by Riken Chemical Industry Co., Ltd.) Or, Oxo Resin (registered trademark) powder (manufactured by Riken Chemical Industry Co., Ltd.) is preferred.

  The combination ratio of adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic product in the medicament of the present invention is not particularly limited, and may be determined by the test method specifically shown in the examples below. A trader can select appropriately. In the present invention, for example, when processed garlic is used as a processed garlic product, adenosine 5′-triphosphate or a physiologically acceptable salt 1 thereof from the viewpoint of synergistic effects of fatigue prevention and / or recovery action With respect to parts by mass, the processed ridge is in the range of 0.006 to 34 parts by mass, more preferably in the range of 0.012 to 17 parts by mass, and still more preferably in the range of 0.06 to 3.4 parts by mass. Is preferably in the range of 0.1 to 2 parts by mass, particularly preferably in the range of 0.12 to 0.42 parts by mass. In the case of using other processed garlic, from the viewpoint of synergistic effect of fatigue prevention and / or recovery action, 1 part by mass of adenosine 5′-triphosphate or a physiologically acceptable salt thereof. The processed garlic is in the range of 0.012 to 3400 parts by mass, more preferably in the range of 0.024 to 1700 parts by mass, further preferably in the range of 0.12 to 340 parts by mass, and more preferably 0 in terms of bulk drug substance. It is preferably used in the range of 2 to 4 parts by mass, particularly preferably in the range of 0.24 to 0.48 parts by mass.

In addition to adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic product, the medicament for preventing and / or recovering fatigue according to the present invention enhances fatigue preventing and / or recovery action. For this purpose, it is preferable to further blend vitamin Bs. The B vitamins, for example, as vitamin B _1, thiamine hydrochloride, thiamine mononitrate, nitrate Bisuchiamin, thiamine disulfide, thiamine dicetyl sulfate ester salts, hydrochloric dicethiamine, fursultiamine hydrochloride, oct thiamine, Shikochiamin, bis Eve thiamine, bis vitamins B _2, flavin adenine dinucleotide sodium, riboflavin, riboflavin sodium phosphate, riboflavin butyrate and the like; bench amine, fursultiamine, prosultiamine, benfotiamine etc. as vitamin B _6, pyridoxine hydrochloride, phosphate pyridoxal etc.; as vitamin B _12, HCl hydroxocobalamin acetate hydroxocobalamin, cyanocobalamin, hydroxocobalamin, mecobalamin, and the like.
In the present invention, from the viewpoint of the synergistic effect of fatigue prevention and / or recovery action, it is preferable to blend one or more vitamin Bs selected from vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , and vitamin B _12. More preferably, two or more kinds of vitamin B selected from vitamin B ₁ , vitamin B ₂ , vitamin B ₆ and vitamin B ₁₂ are blended, from vitamin B ₁ , vitamin B ₂ , vitamin B ₆ and vitamin B ₁₂ It is more preferable to mix three or more kinds of vitamin B selected, and it is particularly preferable to mix 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, but from the viewpoint of the synergistic effect of fatigue prevention and / or recovery action, For example, with respect to 1 part by mass of adenosine 5′-triphosphate or physiologically acceptable salt thereof, vitamin B ₁ is 0.0003-20 parts by mass, vitamin B ₂ is 0.0005-8 parts by mass, vitamin B ₆ is 0.001 to 20 parts by mass, and vitamin B ₁₂ is in the range of 0.0000003 to 0.3 parts by mass, preferably vitamin B ₁ is 0.003 to ₂ parts by mass, vitamin B ₂ is 0.005 to 0 .8 parts by weight vitamin _{B 6} 0.01 to 2 parts by weight, and vitamin _{B 12} are preferably used in the range of 0.000003 to 0.03 parts by weight.

The medicament of the present invention may be either a medicament suitable for oral administration or a medicament suitable for parenteral administration. Preferably, it is a pharmaceutical suitable for oral administration.
A pharmaceutical suitable for oral administration is a solid, semi-solid, or liquid pharmaceutical composition comprising adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic product in one unit dosage form. More preferably, it is provided as a product.

  In providing the medicament of the present invention as a medicament suitable for oral administration or a medicament suitable for parenteral administration, its administration form is not particularly limited. For example, pharmaceutical compositions in solid form such as powders, granules, tablets, chewable tablets, film-coated tablets, dragees, soft capsules and hard capsules, pharmaceutical compositions in the form of solutions such as drinks, or jelly preparations Any of the pharmaceutical compositions in a semi-solid form such as In the present invention, a solid pharmaceutical composition is particularly preferred from the viewpoint of stability and ease of drinking.

In providing the medicament of the present invention as a pharmaceutical composition containing adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic product, the amount of each component in the pharmaceutical composition is particularly limited. Rather, it is determined according to the form of the pharmaceutical composition, taking into account the above-mentioned combination ratio as appropriate. For example, in providing a pharmaceutical composition in a solid form, when using a processed garlic as a processed garlic product, adenosine 5′-triphosphate or a physiologically acceptable salt thereof per unit of the pharmaceutical composition About 1 to 300 mg, and about 1 to 300 mg of processed candy can be blended. In addition, in addition to adenosine 5′-triphosphate or a physiologically acceptable salt thereof and a processed garlic product, vitamin Bs are added, for example, 0.3-100 mg of vitamin B ₁ per unit. extent, about 0.5~50mg vitamin _{B 2,} 1 to 100 mg about vitamin _{B 6,} vitamin _{B 12} may be incorporated about 0.0003～1.5Mg.

The medicament for preventing and / or recovering from fatigue according to the present invention includes adenosine 5′-triphosphate or a physiologically acceptable salt thereof, processed garlic, vitamin B ₁ , vitamin B ₂ , vitamin B _6. Ingredients other than vitamin B such as vitamin B ₁₂ can be appropriately blended according to the blending purpose. Examples of such components include vitamin A, water-soluble vitamins, vitamin D, vitamin E, vitamin-like substances, minerals, caffeine, amino acids, drugs for liver damage, crude drugs, and other components.

  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, dl-α-tocopherol acetate, d-α-tocopherol, dl-α-tocopherol and the like.

  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.

  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-aspartic acid, potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, cysteine 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-methionine, L-phenylalanine, L-tryptophan, etc. are mentioned.

  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, Ezocogi, Ougi, Ousei, Guarana, Kanzo, Kokushi, Keihi, Kojin, Saffron, Hawthorn, Sanyaku, Peonies, Shukusha, Gyoza, Jotei, Hawthorn, Taiso, Clove, Chinpi, Toki, Examples include horse chestnut, eucommia, licorice, carrot, bukkyou, muirapuama, mokko, yakuchi, yokuinin, ryogannik, royal jelly, lokja and the like.

  Examples of other components include placenta.

  The medicament 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 additive for formulation include, but are not limited to, excipients, binders, disintegrants, lubricants, colorants, corrigents, and coating agents.

  Examples of the excipient include lactose, starches, crystalline cellulose, sucrose, mannitol, and light anhydrous silicic acid. Examples of the binder include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, or pullulan. Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, and low-substituted hydroxypropylcellulose. Examples of the lubricant include magnesium stearate or talc. Examples of the colorant include tar pigments and iron sesquioxide. Examples of the corrigent include stevia, aspartame, or a fragrance. Coating agents include film-forming polymers such as carboxymethyl ethyl cellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic acid copolymer LD, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate. Can be used. When forming a film, powders such as plasticizers such as triethyl citrate, triacetin and polyethylene glycol, talc, titanium oxide, yellow ferric oxide, ferric oxide, legal dye, light anhydrous silicic acid, hydrous silicon dioxide Can also be blended.

  The dose of the medicament of the present invention is not particularly limited, and can 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 normal cases, adenosine 5′-triphosphate or a physiologically acceptable salt thereof may be administered to an adult at about 6 to 3000 mg / day, particularly about 20 to 300 mg / day, depending on the dose. Thus, the dose of processed garlic and vitamin B can be determined based on the above-described ratio.

  The administration method of the medicament of the present invention is not particularly limited, and adenosine 5'-triphosphate or a physiologically acceptable salt thereof and a processed garlic product can be administered simultaneously or at different times. When these ingredients are administered at different times, it is desirable to administer other active ingredients within a time period during which the blood concentration of the previously administered active ingredient 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 medicament of the present invention can be used for either physical fatigue such as fatigue accompanying physical load such as exercise load, or mental fatigue such as fatigue caused by mental load such as environmental stress or mental fatigue (central fatigue). Although it is applicable to the present invention, it is preferably applied to physical fatigue in the present invention. The medicament of the present invention has an excellent prevention and / or recovery action against physical fatigue and / or mental fatigue, as shown in Examples below, based on the fatigue prevention and / or recovery action, Alleviation of symptoms such as eye strain, muscle pain, low back pain, stiff shoulders, general malaise, nourishment, nutritional supplementation (eg, physical fatigue, decreased physical fitness after illness, loss of appetite, nutritional disorder, febrile wasting disease, pregnancy Nutritional supplementation during breastfeeding, etc.) and physical strength enhancement can be exerted.

  Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples.

Test example 1
The exercise load experiment was conducted according to the following method.
<Test method>
A 5-week-old BALB / C male mouse was placed in a 20 cm diameter water tank containing water maintained at 22 ° C. on the first day of the test, and the swimming amount (pre value) for 5 minutes was measured. The amount of swimming was expressed as the number of movements to adjacent and diagonal areas when the water surface of the aquarium was divided into four. Thereafter, the test drug was repeatedly administered for 4 days from the first day of the test, and fasted on the evening of the fourth day of the test. On the fifth day of the test, the mice were allowed to swim in the same water tank for 20 minutes, and the test drug was orally administered after the end of the swimming. Then, after standing for 30 minutes, the amount of swimming (post value) for 5 minutes was measured in the same water tank, and the rate of change of swimming amount ((post value / pre value) × 100) was calculated. In addition, the increase in the amount of change in the swimming amount relative to the control (the group administered with 0.5% methylcellulose (hereinafter abbreviated as “MC”)) in the test drug administration group is the increase in swimming amount (= swimming in the test drug administration group It was calculated as (quantity change rate-control average swimming amount change rate).
As test drugs, adenosine 5′-triphosphate disodium (hereinafter abbreviated as “ATP” in the Examples) 120 mg / kg, oxoamidin powder (manufactured by Riken Chemical Co., Ltd.) 50 mg / kg, ATP 120 mg / kg and oxoamidin Using a combination of powder 50 mg / kg (hereinafter abbreviated as “ATP + oxoamidin powder” in the examples), these were suspended or dissolved in 0.5% methylcellulose and used for the test.

<Experimental result>
The results are shown in FIG.

コントロールの平均遊泳量変化率を1.00とした時の各試験群の平均遊泳量変化率を遊泳量相対値として表した。
被験薬物投与群のコントロールに対する遊泳量変化率の増加を遊泳増加量として表した。
N=14〜17
*：p＜0.05 vs コントロール（Dunnett type多重比較）
バルジの方法による相乗効果の判定：1.39(ＡＴＰ＋オキソアミヂン末)＞1.10(ＡＴＰ)×1.14(オキソアミヂン末)

The average swimming amount change rate of each test group when the average swimming amount change rate of the control was 1.00 was expressed as a relative value of the swimming amount.
The increase in the swimming amount change rate relative to the control in the test drug administration group was expressed as the swimming increase amount.
N = 14-17
*: P <0.05 vs control (Dunnett type multiple comparison)
Judgment of synergistic effect by bulge method: 1.39 (ATP + oxoamidin powder)> 1.10 (ATP) x 1.14 (oxoamidin powder)

Test example 2
<Test method>
The test was carried out in the same manner as in Test Example 1, except that the dose of ATP was 120 mg / kg and the dose of oxoamidin powder was 15 mg / kg. The results are shown in FIG.

コントロールの平均遊泳量変化率を1.00とした時の各試験群の平均遊泳量変化率を遊泳量相対値として表した。
被験薬物投与群のコントロールに対する遊泳量変化率の増加を遊泳増加量として表した。
Ｎ＝７
バジルの方法による相乗効果の判定：1.49(ＡＴＰ＋オキソアミヂン末)＞1.05(ＡＴＰ)×1.05（オキソアミヂン末）

The average swimming amount change rate of each test group when the average swimming amount change rate of the control was 1.00 was expressed as a relative value of the swimming amount.
The increase in the swimming amount change rate relative to the control in the test drug administration group was expressed as the swimming increase amount.
N = 7
Judgment of synergistic effect by the method of basil: 1.49 (ATP + oxoamidin powder)> 1.05 (ATP) x 1.05 (oxoamidin powder)

  In comparison with the control group to which MC was administered, a slight increase in the amount of change in swimming amount was observed in the group to which ATP and oxoamidin powder were administered alone, but this was not a significant effect. However, a significant increase in the swimming rate change was observed in the administration group (ATP + oxoamidin powder) of the pharmaceutical of the present invention, and a significant difference was observed in comparison with the control group administered with MC. Further, the rate of increase in the swimming rate change rate relative to the control (swimming amount relative value) was 1.10 in the ATP administration group and 1.14 in the oxoamidin powder administration group in Test Example 1, and the product (1 .25) is smaller than 1.39 of ATP + oxoamidin powder, and in Test Example 2, it is 1.05 in the ATP administration group and 1.05 in the oxoamidin powder administration group, and their product (1.10) is ATP + oxoamidin. The combination of adenosine 5′-triphosphate or a physiologically acceptable salt thereof and garlic product, which is smaller than 1.49 at the end and by bulge method, exhibits a synergistic effect on fatigue prevention and / or recovery action. It was concluded that In addition, the increase in the amount of change in the swimming amount was also observed in the group administered with the pharmaceutical agent of the present invention, compared with the group administered with ATP and oxoamidin powder alone, in the amount of increase in the swimming representing an increase in the amount of change in the amount of swimming from the control. From the above results, the medicament of the present invention has adenosine 5′-triphosphate or a physiologically acceptable salt thereof against physical fatigue caused by physical stress and mental fatigue caused by environmental stress in the aquatic environment. It was revealed that the combined use of garlic processed products has a synergistic fatigue prevention and / or recovery action.

Production Example 1
Adenosine 5'-triphosphate disodium 60.0mg in daily dose (3 tablets)
Oxoamidin powder 50.0mg
Ezoukogi dry extract (powder equivalent amount 300mg) 12.0mg
Ogi dry extract (Drug substance equivalent amount 240mg) 30.0mg
Arginine hydrochloride 50.0mg
Thiamine nitrate 10.0mg
Riboflavin 4.0mg
Pyridoxine hydrochloride 10.0mg
Dl-α-Tocopherol calcium succinate 20.7mg
Sodium ascorbate 112.6mg
Nicotinamide 25.0mg
Anhydrous caffeine 50.0mg
Hardened oil 40.0mg
Hydroxypropylcellulose 24.0mg
Crystalline cellulose 125.7mg
Carmellose 30.0mg
Magnesium stearate 6.0mg
Total 660.0mg

  480 g of adenosine 5′-triphosphate, 400 g of oxoamidin powder, 96 g of dried extract of sorghum, 240 g of dried arginine, 400 g of arginine hydrochloride, 80 g of thiamine nitrate, 32 g of riboflavin, 80 g of pyridoxine hydrochloride, dl-α-tocopherol calcium succinate 165. 6 g, sodium ascorbate 900.8 g, nicotinic acid amide 200 g, anhydrous caffeine 400 g, hydrogenated oil 320 g, hydroxypropylcellulose 192 g, crystalline cellulose 1005.6 g, carmellose 240 g were mixed with a high-speed agitation granulator (Paurek: FM-VG-25 The mixture was put into a mold) and mixed, and 600 g of ethanol was added and kneaded. The kneaded product was dried using a fluidized bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). This granulated product 5232 g and magnesium stearate 48 g were put into a mixer (Kotobuki Giken Kogyo: PM-50) and mixed, and then a tableting machine (Hatetsu Works: HT-) with a 8 mm diameter and 10 mm curvature radius was attached. AP18SS type), one tablet of 220 mg was obtained.

Production Example 2
Daily dose (3 tablets) adenosine 5′-triphosphate disodium 120.0 mg
Oxoamidin powder 50.0mg
Benfotiamine 138.3mg
Riboflavin 12.0mg
Pyridoxine hydrochloride 50.0mg
Cyanocobalamin 60.0μg
Gamma-Oryzanol 10.0mg
Dl-α-tocopherol calcium succinate 103.6 mg
D-mannitol 116.0mg
Crystalline cellulose 120.1mg
Hydroxypropylcellulose 37.5mg
Carmellose calcium 45.0mg
Magnesium stearate 7.5mg
Total 810.0mg

  Adenosine 5′-triphosphate disodium 720 g, oxoamidin powder 300 g, benfotiamine 829.8 g, riboflavin 72 g, pyridoxine hydrochloride 300 g, gamma-oryzanol 60 g, succinate dl-α-tocopherol calcium 621.6 g, D-mannitol 696 g Then, 720.6 g of crystalline cellulose, 225 g of hydroxypropyl cellulose, and 270 g of carmellose calcium were put into a high-speed stirring granulator (Paurek: FM-VG-25 type) and mixed, and 500 g of ethanol in which 360 mg of cyanocobalamin was dissolved in advance was added. The mixture was kneaded and further pulverized and granulated using a granulator (Okada Seiko: ND-10S type). The granulated product was dried using a fluid bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). 4815 g of this sized product and 45 g of magnesium stearate were charged into a blender (Asahi Kogyo: B2 / 109 type) and mixed, and then a tableting machine equipped with a scissors with a diameter of 8.5 mm and a curvature radius of 12 mm (Hata Iron Works: One tablet of 270 mg was obtained using HT-AP18SS type.

Production Example 3
Daily dose (6 tablets) adenosine 5'-triphosphate disodium 60.0mg
Oxoamidin powder 30.0mg
Fursultiamine hydrochloride 20.0mg
Sodium chondroitin sulfate 900.0mg
D-mannitol 125.0mg
Crystalline cellulose 130.0mg
Hydroxypropylcellulose 40.8mg
Carmellose calcium 61.2mg
Magnesium stearate 13.0mg
Total 1380.0mg

  Adenosine 5′-triphosphate disodium 240 g, oxoamidin powder 120 g, fursultiamine hydrochloride 80 g, chondroitin sulfate sodium 3600 g, D-mannitol 500 g, crystalline cellulose 520 g, hydroxypropyl cellulose 163.2 g, carmellose calcium 244.8 g Stirring granulator (Paurek: FM-VG-25 type), mixing, mixing, adding 900g of ethanol, kneading and further granulating using granulator (Okada Seiko: ND-10S type) . The granulated product was dried using a fluid bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). This sized product 5388g and magnesium stearate 52g were put into a blender (Asahi Kogyo: B2 / 109 type) and mixed, and then a tableting machine equipped with a punch having a diameter of 8 mm and a radius of curvature of 12 mm (Hata Iron Works: HT- AP18SS type), 1 tablet of 230 mg was obtained.

Production Example 4
Adenosine 5'-triphosphate disodium 60.0mg in daily dose (3 tablets)
Oxoamidin powder 20.0mg
Carrot extract (powder equivalent amount 600mg) 180.0mg
D-α-Tocopherol acetate 10.0 mg
Bisbentiamine 20.0mg
Riboflavin 10.0mg
Pyridoxine hydrochloride 20.0mg
Cyanocobalamin 20.0μg
Calcium pantothenate 20.0mg
Nicotinamide 20.0mg
Hardened oil 36.0mg
Crystalline cellulose 144.0mg
Hydroxypropylcellulose 24.0mg
Carmellose calcium 30.0mg
Magnesium stearate 6.0mg
Total 600.0mg

  Adenosine 5′-triphosphate disodium 480 g, oxoamidin powder 160 g, carrot extract 1440 g, acetic acid d-α-tocopherol 80 g, bisventamine 160 g, riboflavin 80 g, pyridoxine hydrochloride 160 g, nicotinic acid calcium 160 g, nicotinic acid amide 160 g, cured 288 g of oil, 1152 g of crystalline cellulose, 192 g of hydroxypropyl cellulose, and 240 g of carmellose calcium were put into a high-speed stirring granulator (Paurek: FM-VG-25 type) and mixed, and then 700 g of ethanol in which 160 mg of cyanocobalamin was dissolved in advance was added. The mixture was kneaded and further pulverized and granulated using a granulator (Okada Seiko: ND-10S type). The granulated product was dried using a fluid bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). This granulated product (4752 g) and magnesium stearate (48 g) were put into a mixer (Kotobuki Giken Kogyo: PM-50) and mixed, and then a tableting machine (Hatetsu Works: 8 mm in diameter, 12 mm in curvature radius and 4 mm in radius) was attached. HT-AP18SS type), 200 mg tablets were obtained.

Production Example 5
Adenosine 5'-triphosphate disodium 60.0mg in daily dose (3 tablets)
Oxoamidin powder 30.0mg
Fursultiamine hydrochloride 100.0mg
Pyridoxine hydrochloride 100.0mg
Mecobalamin 1500μg
D-α-Tocopherol acetate 100.0 mg
Hardened oil 36.0mg
Crystalline cellulose 112.5mg
Hydroxypropylcellulose 24.0mg
Carmellose calcium 30.0mg
Magnesium stearate 6.0mg
Methacrylic acid copolymer LD 41.0mg
Talc 12.3mg
Triethyl citrate 6.16mg
Titanium oxide 0.54mg
Total 660.0mg

Adenosine 5′-triphosphate disodium 480 g, oxoamidin powder 240 g, fursultiamine hydrochloride 800 g, pyridoxine hydrochloride 800 g, d-α-tocopherol acetate 800 g, hydrogenated oil 288 g, crystalline cellulose 900 g, hydroxypropyl cellulose 192 g, carmellose calcium 240 g Is added to a high-speed stirring granulator (Paurek: FM-VG-25 type) and mixed, and then 700 g of ethanol in which 12 g of mecobalamin is dissolved in advance is added and kneaded. Further, a granulator (Okada Seiko: ND-10S type). ) For pulverization and granulation. The granulated product was dried using a fluid bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). This granulated product (4752 g) and magnesium stearate (48 g) were put into a mixer (Kotobuki Giken Kogyo: PM-50) and mixed, and then a tableting machine (Hatetsu Works: 8 mm in diameter, 12 mm in curvature radius and 4 mm in radius) was attached. HT-AP18SS type), 200 mg uncoated tablets were obtained.
Purified water 2400g, methacrylic acid copolymer LD410g, talc 123g, triethyl citrate 61.6g, and titanium oxide 5.4g dissolved and dispersed in this uncoated tablet were coated with a breathable coating machine (Doria Coater DRC-650DS type). (Paulec Co., Ltd.) was used to obtain a 220 mg film-coated tablet.

Production Example 6
Adenosine 5'-triphosphate disodium 60.0mg in daily dose (3 tablets)
Oxoamidin powder 20.0mg
Kukosi extract 60.0mg
Toshishi Extract 3.0mg
Royal Jelly 50.0mg
Dehydrocholic acid 10.0mg
Riboflavin 10.0mg
Cyanocobalamin 2.0μg
D-α-Tocopherol acetate 10.0 mg
Nicotinamide 12.0mg
Anhydrous caffeine 50.0mg
Hardened oil 36.0mg
D-mannitol 93.0mg
Crystalline cellulose 120.0mg
Hydroxypropylcellulose 24.0mg
Carmellose 36.0mg
Magnesium stearate 6.0mg
Total 600.0mg

  Adenosine 5′-triphosphate disodium 480 g, oxoamidin powder 160 g, kokushi extract 480 g, toshishi extract 24 g, royal jelly 400 g, dehydrocholic acid 80 g, riboflavin 80 g, d-α-tocopherol acetate 80 g, nicotinamide 96 g, anhydrous caffeine 400 g, 288 g of hardened oil, 744 g of D-mannitol, 960 g of crystalline cellulose, 192 g of hydroxypropyl cellulose, and 288 g of carmellose were charged into a high-speed agitation granulator (Paurek: FM-VG-25 type) and mixed, and ethanol in which 12 mg of cyanocobalamin was dissolved in advance 600 g was added and kneaded. The kneaded product was dried using a fluidized bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). This granulated product (4752 g) and magnesium stearate (48 g) were put into a blender (Kotobuki Giken Kogyo: PM-50) and mixed, and then a tableting machine (Hatetsu Works: HT-) with a diameter of 8 mm and a curvature radius of 12 mm was attached. AP18SS type), 1 tablet 200 mg was obtained.

Production Example 7
Daily dose (6 tablets) adenosine 5'-triphosphate disodium 60.0mg
Oxoamidin powder 200.0mg
Placenta extract 800.0mg
Thiamine nitrate 10.0mg
D-α-Tocopherol acetate 10.0 mg
Carrot extract 60.0mg
Hardened oil 64.0mg
D-mannitol 120.0mg
Crystalline cellulose 155.0mg
Calcium silicate 48.0mg
Hydroxypropylcellulose 60.0mg
Carmellose calcium 84.0mg
Magnesium stearate 9.0mg
Total 1680.0mg

  180 g of adenosine 5′-triphosphate, 600 g of oxoamidin powder, 2400 g of placenta extract, 30 g of thiamine nitrate, 30 g of d-α-tocopherol acetate, 180 g of carrot extract, 192 g of hardened oil, 360 g of D-mannitol, 465 g of crystalline cellulose, silicic acid 144 g of calcium, 180 g of hydroxypropyl cellulose, and 252 g of carmellose calcium were put into a high-speed stirring granulator (Paurek: FM-VG-25 type), mixed, kneaded after adding 700 g of ethanol, and further a granulator (Okada). Seiko: ND-10S type) was used for crushing and granulating. The granulated product was dried using a fluid bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). 4815 g of this sized product and 27 g of magnesium stearate were charged into a blender (Asahi Kogyo: B2 / 109 type) and mixed, and then a tableting machine (Yata Iron Works: 9 mm in diameter and 15.5 mm in radius of curvature) was attached. HT-AP18SS type), 1 tablet of 280 mg was obtained.

Production Example 8
Daily dose (2 tablets) adenosine 5′-triphosphate disodium 120.0 mg
Oxoamidin powder 50.0mg
Thiamine nitrate 30.0mg
Riboflavin 4.0mg
Pyridoxine hydrochloride 24.0mg
Cyanocobalamin 60.0μg
Hardened oil 24.0mg
Crystalline cellulose 100.0mg
Hydroxypropylcellulose 20.0mg
Carmellose calcium 24.0mg
Magnesium stearate 4.0mg
Total 400.0mg

  Adenosine 5′-triphosphate disodium 1440 g, oxoamidin powder 600 g, thiamine nitrate 360 g, riboflavin 48 g, pyridoxine hydrochloride 288 g, hydrogenated oil 288 g, crystalline cellulose 1200 g, hydroxypropyl cellulose 240 g, carmellose calcium 288 g (Pauleck: FM-VG-25 type) was added and mixed, and 600 g of ethanol in which 720 mg of cyanocobalamin was dissolved in advance was added and kneaded. The kneaded product was dried using a fluidized bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). This granulated product (4752 g) and magnesium stearate (48 g) were put into a blender (Kotobuki Giken Kogyo: PM-50) and mixed, and then a tableting machine (Hatetsu Works: HT-) with a diameter of 8 mm and a curvature radius of 14 mm was attached. AP18SS type), 1 tablet 200 mg was obtained.

Production Example 9
Adenosine 5'-triphosphate disodium 60.0mg in daily dose (3 tablets)
Oxoamidin powder 50.0mg
Arginine hydrochloride 50.0mg
Gamma-Oryzanol 10.0mg
Thiamine nitrate 10.0mg
Riboflavin 4.0mg
Pyridoxine hydrochloride 10.0mg
Dl-α-Tocopherol calcium succinate 20.7mg
Retinol palmitate 2000.0 IU
Sodium ascorbate 112.6mg
Nicotinamide 25.0mg
Anhydrous caffeine 50.0mg
Hardened oil 100.9mg
Crystalline cellulose 165.6mg
Hydroxypropylcellulose 37.5mg
Carmellose calcium 65.0mg
Magnesium stearate 7.5mg
Total 780.0mg

  Adenosine 5′-triphosphate disodium 360 g, oxoamidin powder 300 g, arginine hydrochloride 300 g, gamma-oryzanol 60 g, thiamine nitrate 60 g, riboflavin 24 g, pyridoxine hydrochloride 60 g, dl-α-tocopherol calcium succinate 124.2 g, sodium ascorbate 675.6 g, nicotinamide 150 g, anhydrous caffeine 300 g, hydrogenated oil 605.4 g, crystalline cellulose 993.6 g, hydroxypropylcellulose 225 g, carmellose calcium 390 g were mixed with a high-speed agitation granulator (Paurek: FM-VG-25 type) ) Was added and kneaded with 600 g of ethanol in which 7.2 g of retinol palmitate had been dispersed in advance, and further pulverized and granulated using a granulator (Okada Seiko: ND-10S type). The granulated product was dried using a fluid bed dryer (Freund Sangyo: NFLO-5 type) and then sized using a granulator (Okada Seiko: ND-10S type). 4635 g of this sized product and 45 g of magnesium stearate were put into a mixer (Asahi Kogyo: B2 / 109 type) and mixed, and then a tableting machine equipped with a punch having a diameter of 9 mm and a radius of curvature of 12 mm (Hatetsu Works: HT- AP18SS type), 1 tablet of 260 mg was obtained.

Claims (5)

A medicament for preventing and / or recovering from fatigue, comprising simultaneously administering adenosine 5′-triphosphate or a physiologically acceptable salt thereof in combination with processed potato . The medicament 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 processed potato . Additionally, vitamin B _1, vitamin B _2, containing one or more B vitamins selected from vitamin of B ₆ and vitamin B _12, claim 1 or 2 A medicament according.   The medicine according to any one of claims 1 to 3, wherein the fatigue is physical fatigue and / or mental fatigue. A salt thereof adenosine 5'-triphosphate or a physiologically acceptable, combination ratio of the processing garlic is, for that salt 1 part by mass which is A Denoshin 5'-triphosphate or a physiologically acceptable, processed garlic is 0.1 to 2 parts by weight in which claim 1 any one medicament according 4.

Images