JP5961034B2 - Stabilization method - Google Patents

Description

  The present invention relates to a method for stabilizing one or more selected from the group consisting of adenosine triphosphate and a salt thereof.

Adenosine triphosphate (ATP) is a compound having a high-energy phosphate bond, and has the property of releasing a large amount of energy when hydrolyzed into adenosine diphosphate (ADP) and phosphate. It is widely involved in metabolism of carbohydrates, fats, proteins, etc. in the body. In addition, adenosine triphosphate has various pharmacological actions, improvement of various symptoms associated with sequelae of head injury, stabilization of regulatory function in heart failure, regulatory eye strain, chronic gastritis with decreased gastrointestinal function, Meniere In addition to being used as an active ingredient of pharmaceuticals used for vertigo based on diseases and inner ear disorders, it is also known to increase muscle torque and reduce muscle fatigue (Patent Document 1), which is extremely useful. It is a high component.
Furthermore, it is also known that a combination of adenosine triphosphate, vitamin B group and processed garlic has an excellent fatigue recovery action (Patent Documents 2 and 3), and fatigue due to a combination of such vitamins and the like From the recovery action, it is expected to be incorporated into vitamin-containing health medicines and vitamin main drug formulations.

JP-T-2004-535417 International Publication No. WO2006 / 126663 Pamphlet International Publication No. WO2008 / 001494 Pamphlet

However, it is selected from the group consisting of adenosine triphosphate and its salt between one or more selected from the group consisting of adenosine triphosphate and its salt and one or more of the components selected from 1 to 11 below. Until now, it has not been known at all whether or not an interaction that affects one or more kinds of storage stability occurs.
Therefore, in order to develop vitamin-containing health medicines and vitamin main drug preparations containing at least one selected from the group consisting of adenosine triphosphate and salts thereof, various components that can be added to these preparations, adenosine triphosphate and When the present inventors examined the storage stability with one or more selected from the group consisting of the salt, one or more selected from the group consisting of adenosine triphosphate and its salt and the following components 1-11: One of them:
DESCRIPTION OF SYMBOLS 1 Vitamin B1 2 Vitamin B2 3 Vitamin B6 4 Vitamin B12 5 Nicotinic acid 6 Pantothenic acid 7 Vitamin C 8 Garlic processed product 9 Gamma oryzanol 10 Caffeine 11 Arginine (In this specification, said 1 (One or more components selected from ˜11 may be referred to as “interactive components”.)

When these are mixed and stored under high temperature conditions, an unexpected interaction occurs between these components, resulting in a decrease in the content of one or more selected from the group consisting of adenosine triphosphate and its salt. There was found.

  Therefore, the present invention is 1 selected from the group consisting of adenosine triphosphate and a salt thereof, which is produced in the coexistence of one or more selected from the group consisting of adenosine triphosphate and a salt thereof and the interactive component. It is an object of the present invention to provide a method for suppressing a decrease in content of seeds or more.

  As a result of intensive studies to solve the above problems, the present inventors have found that one or more members selected from the group consisting of adenosine triphosphate and salts thereof and the above-mentioned interactive component, and further, from tocopherols and chondroitin sulfate esters It has been found that the coexistence of one or more selected from the group consisting of a group consisting of adenosine triphosphate and a salt thereof suppresses a decrease in the content of one or more selected from the group consisting of adenosine triphosphate and its salt, thereby improving the stability.

  That is, the present invention is also referred to as one or more selected from the group consisting of adenosine triphosphate and a salt thereof (hereinafter also referred to as component (A)) and the interactive component (hereinafter also referred to as component (B)). ) And one or more selected from the group consisting of tocopherols and chondroitin sulfates (hereinafter also referred to as component (C)), and from the group consisting of adenosine triphosphate and salts thereof One or more selected stabilization methods (hereinafter referred to as “the stabilization method of the present invention”) are provided.

  In the present invention, at least one selected from the group consisting of adenosine triphosphate and a salt thereof is the same as at least one selected from the group consisting of the interactive component and tocopherols and chondroitin sulfates. A method for producing a composition with improved stability (hereinafter referred to as “the production method of the present invention”) selected from the group consisting of adenosine triphosphate and a salt thereof, wherein the composition is contained in the composition of Is provided).

  Furthermore, this invention contains 1 or more types chosen from the group which consists of adenosine triphosphate and its salt, the said interactive component, and 1 or more types chosen from the group which consists of tocopherols and chondroitin sulfate ester A composition having improved stability (hereinafter referred to as “the composition of the present invention”) selected from the group consisting of adenosine triphosphate and a salt thereof is provided.

According to the stabilization method of the present invention, it is possible to suppress a decrease in the content of one or more selected from the group consisting of adenosine triphosphate and a salt thereof, and provide a composition with good quality and high commercial value. .
Moreover, according to the production method of the present invention, it is possible to produce a composition having a good quality and a good quality in which a decrease in the content of one or more selected from the group consisting of adenosine triphosphate and a salt thereof is suppressed. .
Furthermore, the composition of the present invention is suppressed in content reduction of one or more selected from the group consisting of adenosine triphosphate and salts thereof, and can be suitably used, for example, as a vitamin-containing health drug or vitamin main drug formulation.

In the present specification, “stabilization” and “improvement of stability” refer to suppression of a decrease in one or more contents selected from the group consisting of adenosine triphosphate and a salt thereof.
First, the stabilization method of the present invention will be described in detail.

<Stabilization method of the present invention>
In the stabilization method of the present invention, “one or more selected from the group consisting of adenosine triphosphate and salts thereof, one or more selected from the group consisting of an interactive component, tocopherols and chondroitin sulfate esters” "Make the coexistence" means, from one or more selected from the group consisting of adenosine triphosphate and a salt thereof, an interactive component, tocopherols and chondroitin sulfate esters, regardless of the order of mixing, etc. It means directly or indirectly creating a state in which one or more selected from the group is present in the same system (for example, in the same composition, in the same closed system, etc.). Therefore, in addition to positively presenting the above three types of components in the same system, the present invention also includes a case where the above three types of components are present in the same system due to changes in the components and the like. Included in the stabilization method. Examples of the coexistence of one or more selected from the group consisting of such tocopherols and chondroitin sulfates include, for example, one or more selected from the group consisting of adenosine triphosphate and a salt thereof, and an interactive component And one or more selected from the group consisting of tocopherols and chondroitin sulfates in the same composition (hereinafter, this embodiment is referred to as “composition stabilization method”) is preferred. .

(Ingredient (A))
The “one or more selected from the group consisting of adenosine triphosphate and a salt thereof” used in the present invention includes not only a free form of adenosine triphosphate but also a physiologically acceptable salt of adenosine triphosphate (for example, Alkali metal salts such as sodium salt and potassium salt of adenosine triphosphate; alkaline earth metal salts such as magnesium salt and calcium salt of adenosine triphosphate), and also adenosine triphosphate and its physiologically acceptable In the present invention, these salts can be used alone or in combination of two or more. Among these, adenosine triphosphate disodium is preferable, and adenosine triphosphate disodium described in Japanese Pharmacopoeia Standard 2002 is particularly preferable.
In addition, adenosine triphosphate, its salt, and those solvates are well-known compounds, and a commercially available thing may be used and it can also manufacture by a well-known method.

In the method for stabilizing a composition of the present invention, the content of one or more selected from the group consisting of adenosine triphosphate and a salt thereof in the composition is not particularly limited, and is appropriately determined depending on the purpose of use of the composition, etc. Selectable. For example, in the case of a composition for oral administration, one or more selected from the group consisting of adenosine triphosphate and a salt thereof per day in total is about 1 to 1000 mg, more preferably about 7.5 to 700 mg, particularly preferably. Can contain an amount of about 15 to 360 mg.
In the method for stabilizing a composition of the present invention, a total of 0.01 to 80% by mass of one or more selected from the group consisting of adenosine triphosphate and a salt thereof is contained with respect to the total mass of the composition. Preferably, 0.05 to 60% by mass is contained, more preferably 1 to 40% by mass, further preferably 2.5 to 40% by mass, and 4 to 40% by mass. Is particularly preferred.

(Ingredient (B))
In the present invention, “vitamin B1” includes not only thiamine itself but also derivatives thereof (bisthiamine, thiamine disulfide, dicetiamine, fursultiamine, octothiamine, chicotiamine, bisivethiamine, bisbenchamine, prosultiamine, benfo. Thiamine, thiamine diphosphate and the like) and salts thereof (inorganic acid salts such as nitrate, hydrochloride and sulfate) are also included, and these can be used alone or in combination of two or more. Among these, in the present invention, thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salt, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, chicotiamine, bisbutiamine, bisbenchamine, full One or more selected from the group consisting of sultiamine, prosultiamine and benfotiamine is preferred, one or more selected from the group consisting of thiamine nitrate, fursultiamine hydrochloride and benfotiamine is more preferred, and fursultiamine hydrochloride And at least one selected from the group consisting of benfotiamine is particularly preferred. These vitamin B1s are known compounds, and commercially available products may be used, or they can be produced by known methods.

  In the present invention, the ratio of the amount used of one or more selected from the group consisting of adenosine triphosphate and its salt and vitamin B1 is not particularly limited, but it is selected from the group consisting of adenosine triphosphate and its salt. Vitamin B1 class 0.001-20 mass part is preferable with respect to 1 or more types of total 1 mass part, 0.005-5 mass part is more preferable, 0.01-3 mass part is more preferable, 0.1-3 mass part is more preferable. 2.5 parts by mass is particularly preferred.

In the method for stabilizing a composition of the present invention, the content of vitamin B1 in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, vitamin B1 of about 0.1 to 1000 mg per day, more preferably about 0.5 to 300 mg, particularly preferably about 1 to 200 mg should be included. Can do.
In the method for stabilizing a composition of the present invention, vitamin B1 is preferably contained in an amount of 0.005 to 60% by mass, more preferably 0.01 to 40% by mass, based on the total mass of the composition. 0.05 to 35% by mass is more preferable, and 1 to 35% by mass is particularly preferable.

  In the present invention, “vitamin B2” includes not only riboflavin itself but also derivatives thereof (riboflavin phosphate, riboflavin butyrate, flavin adenine dinucleotide, etc.) and salts thereof (alkali metal salts such as sodium salt). In the present invention, these can be used alone or in combination of two or more. Among these, in the present invention, at least one selected from the group consisting of flavin adenine dinucleotide sodium, riboflavin, sodium riboflavin phosphate and riboflavin butyrate is preferable, and riboflavin is particularly preferable. These vitamin B2s are known compounds, and commercially available products may be used, or they can be produced by known methods.

  In the present invention, the ratio of the amount used of one or more selected from the group consisting of adenosine triphosphate and its salt and vitamin B2 is not particularly limited, but it is selected from the group consisting of adenosine triphosphate and its salt. Vitamin B2 class 0.001-10 mass part is preferable with respect to 1 or more types of total 1 mass part, 0.005-2 mass part is more preferable, 0.01-1.5 mass part is further more preferable, and 0.1. 1-1 mass parts is particularly preferable.

In the method for stabilizing a composition of the present invention, the content of vitamin B2 in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, vitamin B2 per day is contained in an amount of about 0.1 to 450 mg, more preferably about 0.5 to 100 mg, particularly preferably about 1 to 50 mg. Can do.
In the method for stabilizing a composition of the present invention, vitamin B2 is preferably contained in an amount of 0.005 to 60% by mass, more preferably 0.01 to 40% by mass, based on the total mass of the composition. 0.05 to 35% by mass is more preferable, and 15 to 35% by mass is particularly preferable.

  In the present invention, “vitamin B6” includes pyridoxine, pyridoxamine, pyridoxal itself, derivatives thereof (such as pyridoxal phosphate) and salts thereof (alkaline earth metal salts such as calcium salts; inorganic salts such as hydrochlorides). Acid salts etc.) are also included, and in the present invention, these may be used alone or in combination of two or more. Among these, in the present invention, at least one selected from the group consisting of pyridoxine hydrochloride and pyridoxal phosphate is preferable, and pyridoxine hydrochloride is particularly preferable. These vitamin B6s are known compounds, and commercially available products may be used, or they can be produced by known methods.

  In the present invention, the ratio of the amount used of one or more selected from the group consisting of adenosine triphosphate and its salt and vitamin B6 is not particularly limited, but it is selected from the group consisting of adenosine triphosphate and its salt. Vitamin B6 class 0.005-20 mass parts is preferable with respect to 1 or more types of total 1 mass part, 0.01-10 mass parts is more preferable, 0.02-5 mass parts is further more preferable, 0.1-5 mass parts 2 parts by mass is particularly preferred.

In the method for stabilizing a composition of the present invention, the content of vitamin B6 in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, it should contain an amount of vitamin B6 that can be taken about 0.5 to 1000 mg, more preferably about 1 to 500 mg, particularly preferably about 2.5 to 100 mg per day. Can do.
In the method for stabilizing a composition of the present invention, vitamin B6 is preferably contained in an amount of 0.005 to 90% by mass, more preferably 0.01 to 70% by mass, based on the total mass of the composition. 0.05 to 60% by mass is more preferable, 0.1 to 40% by mass is more preferable, and 15 to 40% by mass is particularly preferable.

  In the present invention, “vitamin B12” includes cyanocobalamin, hydroxocobalamin itself, derivatives thereof (mecobalamin, deoxyadenosylcobalamin, etc.) and salts thereof (inorganic acid salts such as hydrochloride; organic salts such as acetate) Acid salts etc.) are also included, and in the present invention, these may be used alone or in combination of two or more. Among these, in the present invention, at least one selected from the group consisting of hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, mecobalamin and hydroxocobalamin is preferable, and cyanocobalamin is particularly preferable. These vitamin B12s are known compounds, commercially available ones may be used, and they can be produced by known methods.

  In the present invention, the ratio of the amount used of one or more selected from the group consisting of adenosine triphosphate and its salt and vitamin B12 is not particularly limited, but it is selected from the group consisting of adenosine triphosphate and its salt. Vitamin B12 class 0.000001-1 part by mass is preferable, 0.00001-0.5 part by mass is more preferable, and 0.0001-0.1 part by mass is more preferable with respect to 1 part or more in total of 1 type or more. 0.0005-0.05 mass part is especially preferable.

In the method for stabilizing a composition of the present invention, the content of vitamin B12 in the composition is not particularly limited, and can be appropriately selected depending on the purpose of use of the composition. For example, in the case of a composition for oral administration, the amount of vitamin B12 per day is about 0.0001 to 50 mg, preferably about 0.001 to 50 mg, more preferably about 0.0005 to 10 mg, and more preferably 0. About 0.005 to 10 mg, more preferably about 0.001 to 5 mg, and particularly preferably about 0.01 to 5 mg can be contained.
In the method for stabilizing a composition of the present invention, vitamin B12 is preferably contained in an amount of 0.00005 to 2% by mass, more preferably 0.0001 to 1% by mass, based on the total mass of the composition. , 0.0005 to 0.5 mass% is more preferable, and 0.05 to 0.5 mass% is particularly preferable.

  In the present invention, “nicotinic acids” include nicotinic acid, nicotinic acid amide itself, derivatives thereof (inositol hexanicotinate, nicotinic acid amide adenine dinucleotide, nicotinic acid amide adenine dinucleotide phosphate, hepronicart, etc.) and These salts are also included, and in the present invention, these can be used alone or in combination of two or more. Among these, in the present invention, at least one selected from the group consisting of nicotinic acid, nicotinic acid amide, inositol hexanicotinate and hepronicart is preferable, and nicotinic acid amide is particularly preferable. These nicotinic acids are known compounds, which may be commercially available, or can be produced by known methods.

  In the present invention, the ratio of the amount of nicotinic acids used with at least one selected from the group consisting of adenosine triphosphate and its salt is not particularly limited, but 1 selected from the group consisting of adenosine triphosphate and its salt. 0.01-15 mass parts of nicotinic acids are preferable with respect to a total of 1 mass part or more of seeds, more preferably 0.05-3 mass parts, and particularly preferably 0.1-2 mass parts.

In the method for stabilizing a composition of the present invention, the content of nicotinic acids in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, nicotinic acids per day can be contained in an amount of about 1 to 600 mg, more preferably about 5 to 150 mg, and particularly preferably about 10 to 100 mg.
In the method for stabilizing the composition of the present invention, the nicotinic acids are preferably contained in an amount of 0.005 to 60% by mass, more preferably 0.05 to 50% by mass, based on the total mass of the composition. More preferably, it is contained in an amount of 0.1 to 40% by mass, more preferably 0.5 to 35% by mass, and particularly preferably 15 to 35% by mass.

  In the present invention, “pantothenic acids” include pantothenic acid itself, derivatives thereof (panthenol, panthetin, pantethein, coenzyme A and the like) and salts thereof (alkali metal salts such as sodium salts; alkalis such as calcium salts) In the present invention, these can be used alone or in combination of two or more. Among these, in the present invention, at least one selected from the group consisting of panthenol, pantethine, calcium pantothenate and sodium pantothenate is preferable, and calcium pantothenate is particularly preferable. These pantothenic acids are known compounds, commercially available ones may be used, and they can be produced by known methods.

  In the present invention, the ratio of the amount of pantothenic acids used with at least one selected from the group consisting of adenosine triphosphate and its salt is not particularly limited, but 1 selected from the group consisting of adenosine triphosphate and its salt. The pantothenic acids are preferably 0.005 to 5 parts by mass, more preferably 0.02 to 2 parts by mass, still more preferably 0.05 to 1.5 parts by mass, with respect to a total of 1 part by mass of the seeds or more. 1 part by mass is particularly preferred.

In the method for stabilizing a composition of the present invention, the content of pantothenic acids in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, an amount of pantothenic acids that can be taken per day is about 0.5 to 300 mg, more preferably about 2.5 to 100 mg, and particularly preferably about 5 to 50 mg. it can.
In the method for stabilizing a composition of the present invention, pantothenic acids are preferably contained in an amount of 0.005 to 60% by mass, more preferably 0.01 to 50% by mass, based on the total mass of the composition. It is more preferable to make it contain 0.05-40 mass%, It is more preferable to contain 0.1-35 mass%, It is especially preferable to contain 1-35 mass%.

  In the present invention, “vitamin C” includes not only ascorbic acid itself, but also salts thereof (alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt), In this invention, these can be used individually or in combination of 2 or more types. Among these, in this invention, 1 or more types chosen from the group which consists of ascorbic acid, sodium ascorbate, and calcium ascorbate is preferable, and sodium ascorbate is especially preferable. These vitamin Cs are known compounds, and commercially available products may be used, or they can be produced by known methods.

  In the present invention, the ratio of the amount used of one or more selected from the group consisting of adenosine triphosphate and its salt and vitamin C is not particularly limited, but it is selected from the group consisting of adenosine triphosphate and its salt. Vitamin Cs of 0.01 to 100 parts by weight are preferable, 0.1 to 60 parts by weight are more preferable, 0.5 to 40 parts by weight are further preferable, and 0.5 to 5 mass parts is further more preferable, and 0.5-2 mass parts is especially preferable.

In the method for stabilizing a composition of the present invention, the content of vitamin C in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, vitamin C can be contained in an amount that can be taken about 1 to 5000 mg, preferably about 10 to 3000 mg, particularly preferably about 50 to 2000 mg per day.
In the method for stabilizing a composition of the present invention, vitamin C is preferably contained in an amount of 0.005 to 90 mass%, more preferably 0.05 to 70 mass%, based on the total mass of the composition. , 0.5 to 60% by mass is more preferable, 1 to 50% by mass is more preferable, and 15 to 35% by mass is particularly preferable.

In the present invention, any “garlic processed product” may be used as long as it is obtained by processing garlic (Allium sativum). The use site of garlic is not particularly limited, and the whole plant or a part thereof (aboveground, underground, bulb, leaf, stem, flower, etc.) or a combination of two or more thereof can be used, but a bulb is used. Is preferred.
In addition, “processing” includes heating, drying, pulverization, extraction, and the like, and the type of the processing is not particularly limited. Specifically, for example, heat treatment; raw garlic is dried and powdered Extraction treatment with oil, water, hot water or a water-soluble organic solvent, etc. are mentioned. Examples of the oil used for extraction include edible vegetable oils such as rapeseed oil, olive oil, and soybean oil. Examples of the water-soluble organic solvent include lower alcohols such as ethanol and isopropanol; glycols such as propylene glycol and diethylene glycol.

  In the present invention, the processed garlic includes, for example, processed potato, garlic extract, garlic extract, dried garlic and the like, and processed potato is preferred. For example, oxoamidin (registered trademark), oxoamidin (registered trademark) powder, oxoresin (registered trademark) powder (manufactured by Riken Chemical Industry Co., Ltd.) and the like are commercially available. As garlic extract, for example, garlic extract (manufactured by Alps Pharmaceutical Co., Ltd.), garlic extract (manufactured by Nippon Powder Chemical Co., Ltd.) and the like are commercially available. As dried garlic, for example, garlic powder, roasted garlic powder EX (manufactured by Riken Chemical Industry Co., Ltd.) and the like are commercially available. Among these processed garlic products, oxoamidin (registered trademark), oxoamidin (registered trademark) powder and oxoresin (registered trademark) powder are preferable, and oxoamidin (registered trademark) powder is particularly preferable.

  In the present invention, the ratio of one or more selected from the group consisting of adenosine triphosphate and its salt and the amount of garlic processed product used is not particularly limited, but 1 selected from the group consisting of adenosine triphosphate and its salt. The garlic processed product is preferably 0.02 to 40 parts by mass, more preferably 0.1 to 8 parts by mass, and particularly preferably 0.2 to 3 parts by mass with respect to a total of 1 part by mass of the seeds or more.

In the method for stabilizing a composition of the present invention, the content of the processed garlic in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, the amount of garlic processed product that can be taken per day is about 2 to 2000 mg, more preferably about 10 to 400 mg, and particularly preferably about 20 to 200 mg.
In the method for stabilizing a composition of the present invention, the processed garlic product is preferably contained in an amount of 0.005 to 70% by mass, more preferably 0.1 to 60% by mass, based on the total mass of the composition. , 0.5 to 50% by mass is more preferable, and 1 to 35% by mass is particularly preferable.

  “Gamma-Oryzanol” is obtained from rice (Oryza sativa L.) seed coat and the like, and is mainly composed of ferulic acid (3-methoxy-4-hydroxycinnamic acid) ester of triterpene alcohol. In the present invention, the raw material, purification method, production method and the like of gamma-oryzanol are not particularly limited, but gamma-oryzanol described in Quasi-drug raw material standard 2006 is preferable. Gamma-oryzanol is a known component, and a commercially available product may be used, or it can be produced by a known method.

  In the present invention, the ratio of the amount of one or more selected from the group consisting of adenosine triphosphate and its salt to gamma-oryzanol is not particularly limited, but 1 selected from the group consisting of adenosine triphosphate and its salt. 0.005 to 5 parts by mass of gamma-oryzanol is preferable, more preferably 0.02 to 2 parts by mass, and particularly preferably 0.05 to 1 part by mass with respect to a total of 1 part by mass of the seeds or more.

In the method for stabilizing a composition of the present invention, the content of gamma-oryzanol in the composition is not particularly limited, and can be appropriately selected depending on the purpose of use of the composition. For example, in the case of a composition for oral administration, it may contain about 0.5 to 100 mg, more preferably about 2.5 to 50 mg, particularly preferably about 5 to 30 mg of gamma oryzanol per day. it can.
In the method for stabilizing a composition of the present invention, gamma oryzanol is preferably contained in an amount of 0.005 to 60% by mass, more preferably 0.01 to 50% by mass, based on the total mass of the composition. It is more preferable to contain 0.05-40 mass%, it is more preferable to contain 0.1-35 mass%, and it is especially preferable to contain 0.5-35 mass%.

  In the present invention, “caffeine” includes caffeine itself and salts thereof (for example, those forming a double salt (sodium benzoate caffeine (double salt of sodium benzoate and caffeine), etc.), and the like. In the present invention, these can be used singly or in combination of two or more, and among them, caffeine hydrate is used in the present invention. , One or more selected from the group consisting of anhydrous caffeine, sodium benzoate caffeine and caffeine citrate are preferred, and anhydrous caffeine is particularly preferred, since these caffeines are known compounds and are commercially available. It may be used, and can also be produced by a known method.

  In the present invention, the ratio of the amount of caffeine used with at least one selected from the group consisting of adenosine triphosphate and its salt is not particularly limited, but it is selected from the group consisting of adenosine triphosphate and its salt. Caffeine is preferably 0.01 to 5 parts by mass, more preferably 0.1 to 3 parts by mass, and particularly preferably 0.3 to 2 parts by mass with respect to one or more types in total of 1 part by mass.

In the method for stabilizing a composition of the present invention, the content of caffeine in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, about 1 to 300 mg of caffeine per day, more preferably about 10 to 200 mg, still more preferably about 20 to 100 mg, particularly preferably about 30 to 80 mg. An amount that can be contained can be included.
In the method for stabilizing a composition of the present invention, caffeine is preferably contained in an amount of 0.005 to 60% by mass, more preferably 0.05 to 40% by mass, based on the total mass of the composition. , 0.5 to 37.5% by mass is more preferable, 1 to 35% by mass is further preferable, and 15 to 35% by mass is particularly preferable.

In the present invention, “arginine” includes not only arginine itself but also a salt thereof (alkali metal salt such as sodium salt: inorganic acid salt such as hydrochloride). In the present invention, these are independently used. Alternatively, two or more kinds can be used in combination. The “arginine” may be either L-arginine or D-arginine, or a mixture thereof, but L-arginine is preferred in the present invention.
Among the arginines as described above, in the present invention, one or more selected from the group consisting of arginine and arginine hydrochloride is preferable, and arginine hydrochloride is more preferable.
These arginines are known compounds, and commercially available products may be used, or they can be produced by known methods.

  In the present invention, the ratio of the amount used of one or more selected from the group consisting of adenosine triphosphate and a salt thereof and arginine is not particularly limited, but 1 selected from the group consisting of adenosine triphosphate and a salt thereof. 0.01-5 mass parts of arginines are preferable with respect to a total of 1 mass part or more of seeds, more preferably 0.05-3 mass parts, and particularly preferably 0.1-2 mass parts.

In the method for stabilizing a composition of the present invention, the content of arginines in the composition is not particularly limited, and can be appropriately selected according to the purpose of use of the composition. For example, in the case of a composition for oral administration, the total amount of arginines per day that can be taken is about 1 to 300 mg, more preferably about 5 to 200 mg, and particularly preferably about 10 to 80 mg.
In the method for stabilizing a composition of the present invention, arginine is preferably contained in an amount of 0.005 to 60% by mass, more preferably 0.05 to 40% by mass, based on the total mass of the composition. More preferably, it is contained in an amount of 0.1 to 37.5% by mass, more preferably 0.2 to 35% by mass, and particularly preferably 15 to 35% by mass.

(Ingredient (C))
In the present invention, “tocopherols” include d-α-tocopherol, l-α-tocopherol and a mixture thereof (dl-α-tocopherol) itself, and derivatives thereof (tocopherol acetate, tocopherol succinate, nicotinic acid). Tocopherols) and salts thereof (alkaline earth metal salts such as calcium salts) are also included, and in the present invention, these can be used alone or in combination of two or more.
Among the tocopherols as described above, in the present invention, d-α-tocopherol succinate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, d-α-tocopherol acetate, dl-α acetate -1 or more types chosen from the group which consists of tocopherol, d-alpha-tocopherol, dl-alpha-tocopherol, and dl-alpha-tocopherol nicotinate are preferred, from dl-alpha-tocopherol calcium succinate and dl-alpha-tocopherol acetate One or more selected from the group consisting of
These tocopherols are known compounds, and commercially available products may be used, or they can be produced by known methods.

  In the present invention, the ratio of the amount of one or more selected from the group consisting of adenosine triphosphate and its salt to tocopherols is not particularly limited, but 1 selected from the group consisting of adenosine triphosphate and its salt. From the viewpoint of the inhibitory effect on the content decrease of the species or more, 0.001 to 10 parts by mass of tocopherols is preferable with respect to a total of 1 part by mass of one or more selected from the group consisting of adenosine triphosphate and salts thereof. 005-10 mass parts is more preferable, 0.01-10 mass parts is further more preferable, 0.1-5 mass parts is further more preferable, 0.5-1.5 mass parts is further more preferable, 0.9-1. 5 parts by mass is more preferable, and 0.95 to 1.25 parts by mass is particularly preferable.

  Further, in the method for stabilizing a composition of the present invention, the content of tocopherols in the composition is not particularly limited, and it is an inhibitory effect on content decrease of one or more selected from the group consisting of adenosine triphosphate and a salt thereof. The tocopherols are preferably contained in an amount of 0.005 to 60% by mass, more preferably 0.01 to 55% by mass, based on the total mass of the composition. It is more preferable to make it contain 05-40 mass%, and it is especially preferable to contain 1-35 mass%.

In the present invention, “chondroitin sulfate A” includes chondroitin sulfate A, dermatan sulfate, chondroitin sulfate C, chondroitin sulfate D, chondroitin sulfate E, and a mixture thereof, as well as their salts ( Also included are alkali metals such as sodium, potassium, calcium, magnesium, iron and manganese, metal salts such as alkaline earth metals and transition metals; ammonium salts and the like. In the present invention, these are used alone or in combination of two or more. Can be used in combination.
Among the chondroitin sulfates as described above, in the present invention, a chondroitin sulfate free form, a chondroitin sulfate potassium salt, a chondroitin sulfate sodium salt, and a chondroitin sulfate calcium salt are selected from the group consisting of 1 More than one species are preferred, sodium salt of chondroitin sulfate is more preferred, and “sodium chondroitin sulfate” described in Japanese Pharmacopoeia Pharmaceutical Standard 2002 is particularly preferred.
These chondroitin sulfates are known compounds, and commercially available products may be used, or they can be produced by known methods.

  In the present invention, the ratio of the amount used of one or more selected from the group consisting of adenosine triphosphate and its salt and chondroitin sulfate is not particularly limited, but it is selected from the group consisting of adenosine triphosphate and its salt. From the viewpoint of the inhibitory action of the content reduction of one or more kinds, the chondroitin sulfates 0.00001 to 100 parts by weight with respect to a total of 1 part by weight selected from the group consisting of adenosine triphosphate and a salt thereof. Preferably, 0.00005-80 mass parts is more preferable, 0.0001-50 mass parts is more preferable, 0.0005-30 mass parts is further more preferable, 0.001-20 mass parts is further more preferable, 5 parts by mass is more preferred, 0.5 to 1.5 parts by mass is more preferred, 0.9 to 1.5 parts by mass is more preferred, 0.95 Particularly preferably 1.25 parts by mass.

  Further, in the method for stabilizing a composition of the present invention, the content of chondroitin sulfates in the composition is not particularly limited, and the content of one or more kinds selected from the group consisting of adenosine triphosphate and a salt thereof is reduced. Although it can be appropriately selected depending on the inhibitory action, it is preferable to contain chondroitin sulfates in an amount of 0.0005 to 90% by mass, more preferably 0.001 to 85% by mass, based on the total mass of the composition. Preferably, 0.005 to 80% by mass is contained, more preferably 0.01 to 70% by mass, further preferably 0.05 to 50% by mass, and preferably 1 to 35% by mass. It is particularly preferable to let it lie.

In the method for stabilizing a composition of the present invention, in addition to the above-mentioned components, other drugs and Chinese medicine prescriptions can be added to the composition depending on the purpose of use.
Specific examples of the other drugs include retinols (retinol acetate, retinol palmitate, vitamin A oil, etc.), liver oils (liver oil, strong liver oil, etc.), vitamin Ds (ergocalciferol, cholecalciferol). Ursodeoxycholic acid, amino acids (L-cysteine hydrochloride, L-cysteine, L-lysine lysine, L-methionine, DL-methionine, L-isoleucine, L-leucine, L-phenylalanine, L-threonine, L) -Tryptophan, L-valine, aminoethylsulfonic acid, etc.), orotic acid, calcium salts (such as calcium glycerophosphate, calcium gluconate, precipitated calcium carbonate, calcium lactate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, calcium citrate) , Magnesium salts ( Magnesium acid, etc.), glucuronic acids (glucuronolactone, glucuronic acid amide, etc.), dichloroacetic acid diisopropylamine, liver hydrolyzate, carrots (carrots), yokuinin (yokuyin), yakuyaku, rokjo (deer), hampi (antinasal) , Goo (oxen), royal jelly, goose (yellow spirit), wolfberry, oyster, touki (to home), bowie (previously), taisou (large coral), peonies (glaze), gyoza ( Ginger), Ezokogi (Tomogoka), Ougi (Yellow Panther), Kojin (Red Sea bream), Kaikujin (Haijin Kidney), Kashou (What Necklace), Guarana, Psycho (Shibahu), Senkyu (river cucumber), Krategusu, Bukuryu (Ii), methylmethionine sulfonium chloride, inositol, carnitine chloride, rutin, decongestant Minutes (epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride), methylsulfate neostigmine, anti-inflammatory and astringent components (epsilon-aminocaproic acid, allantoin, berberine chloride, sulfuric acid) Berberine, sodium azulenesulfonate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate, lysozyme chloride), antihistamines (diphenhydramine hydrochloride, chlorpheniramine maleate), sulfa drugs (sulfamethoxazole, sulfamethoxazole sodium) , Sulfisoxazole, sulfisomidine sodium), inorganic salts (potassium chloride, calcium chloride, sodium chloride, sodium bicarbonate, charcoal) Acid sodium, dry sodium carbonate, magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, etc., thickeners (polyvinyl alcohol, polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl methylcellulose, glucose, methylcellulose, etc.) ), Alkylpolyaminoethylglycine, boric acid, and the like, and these can be used alone or in combination of two or more.

  Specific examples of Kampo prescriptions include Kamishoyosan (Kamiensan), Hotchu Uekki Tou (Hochuekki-to), Ricken Shito (Rikkunshi-to), Kamiki Hitou (Kamiki Shui-to), Juzentai Hotto ( Juzen Daiyuto), Shokenchutou (Kokenchuyu), Hachimi-ogan (Hachimi-jio-maru), Seishin Renshiin (Seishin Renko Drink), etc. are used alone or in combination of two or more. Can be used.

  In the method for stabilizing a composition of the present invention, the “composition” may be in the form of a solid, semi-solid, or liquid, and depending on the purpose of use, etc. In addition, it can have a shape usually used in foods and the like. Specifically, for example, tablets (including chewable tablets, effervescent tablets, orally disintegrating tablets), troches, drops, hard capsules, soft capsules, granules, powders, fine granules, pills, dry syrup Solid preparations such as suppositories, suppositories, poultices, plasters; lozenges, chewing gums, jelly agents, jelly drops, whipped agents, ointments, creams, foams, inhalers, nazar gels, etc. Semi-solid preparations; syrups, drinks, suspensions, spirits, liquids, eye drops, aerosols, sprays, sprays, and other liquid preparations, etc. It can be made into a dosage form.

  In the method for stabilizing the composition of the present invention, a solid composition is preferable, and solid preparations such as tablets, capsules (excluding liquid-filled capsules), pills, granules, powders, fine granules, etc. Is more preferable, and a tablet is particularly preferable.

  The composition obtained by the method for stabilizing a composition of the present invention is a known method in the pharmaceutical field, quasi-drug field, cosmetic field, food field, etc. according to the specific shape, for example, the 15th revised Japan It can be produced according to the method described in the Pharmacopoeia General Rules for Preparations. For example, when the shape of the composition is a tablet, it is mixed or granulated based on a known method using various commonly used formulation additives, and the resulting mixture or granulated product is optionally mixed with a lubricant. Tableting may be performed after mixing. Furthermore, if desired, a sugar-coating liquid or a film-coating liquid can be used to form a sugar-coated tablet or a film-coated tablet based on a known method.

Specific examples of formulation additives include excipients, binders, disintegrants, lubricants, and the like.
Examples of the excipient include fructose, lactose, starches, crystalline cellulose, sucrose, mannitol and the like.
Examples of the binder include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, pullulan and the like.
Examples of the disintegrant include carmellose, carmellose calcium, sodium carboxymethyl starch, low-substituted hydroxypropylcellulose, crospovidone, croscarmellose sodium, and the like.
Examples of the lubricant include sucrose fatty acid ester, hardened oil, stearic acid, magnesium stearate, talc and the like.

  The composition obtained by the method for stabilizing a composition of the present invention can be used by oral administration or parenteral administration such as rectal or vaginal depending on the purpose of use. In the present invention, oral administration is preferred. In addition, when the composition of the present invention is orally administered, for example, the composition can be divided into about 1 to 4 times per day and taken before meals, between meals, after meals, before going to bed.

  The composition obtained by the method for stabilizing a composition of the present invention can be used as a pharmaceutical, a quasi-drug, a cosmetic, a food, and the like. Depending on the action of the components contained in the composition, for example, a vitamin main drug formulation, vitamin It can be used as a contained health medicine. More specifically, for example, based on the action of the ingredients contained in the composition, neuralgia, muscle pain / joint pain (back pain, stiff shoulders, fifty shoulders, etc.), numbness of limbs, constipation, eye strain, stomatitis, cheilitis, cheilitis, Stomatitis, glossitis, eczema, dermatitis, rash, sore, acne, skin irritation, red nose, redness of eyes, itching of eyes, itching of shoulders / neck streaks due to peripheral blood circulation disorders, numbness / coldness of limbs, Alleviation of various symptoms such as shimoyake; Relief of various symptoms such as shoulder / neck streaks, coldness, numbness of limbs and hot flashes in menopause; irregular menstruation; physical fatigue, pregnancy / lactation period, physical strength decline after sickness, old age It can be used as a medicine for supplementation of vitamins and quasi-drugs.

<Production method of the present invention>
Next, the manufacturing method of this invention is demonstrated.

In the production method of the present invention, at least one selected from the group consisting of adenosine triphosphate and a salt thereof is the same as at least one selected from the group consisting of an interactive component, tocopherols and chondroitin sulfate esters. It is characterized in that it is contained in the composition. In such a production method, there are no particular limitations on the order of blending of the above three components into the composition.
According to the production method, one or more kinds selected from the group consisting of adenosine triphosphate and a salt thereof in the composition can be suppressed, and one kind selected from the group consisting of adenosine triphosphate and a salt thereof. A composition having improved stability in the above composition can be produced.
In the production method of the present invention, the meaning of each word, the amount of each component used, the addition method, and the like are the same as those in the method for stabilizing the composition.

<Composition of the present invention>
Next, the composition of the present invention will be described.

The composition of the present invention contains one or more selected from the group consisting of adenosine triphosphate and salts thereof, an interactive component, and one or more selected from the group consisting of tocopherols and chondroitin sulfates. To do.
The composition has high commercial value because a decrease in the content of one or more selected from the group consisting of adenosine triphosphate and a salt thereof in the composition is suppressed and stability is improved.
In the composition of the present invention, the meaning of each word, the amount of each component used, the method of addition, and the like are the same as in the case of the method for stabilizing the composition.

  EXAMPLES The present invention will be specifically described below using examples, but the present invention is not limited to these examples.

[Test Example 1] Examination of the inhibitory effect of dl-α-tocopherol calcium succinate on the decrease in the content of disodium adenosine triphosphate The stability of the content of disodium adenosine triphosphate under high temperature conditions (content Confirmed).
After preparing the samples of Reference Examples 1 and 2, Comparative Examples 1 to 12, and Examples 1 to 12 shown below, each sample was stored at 80 ° C. for 3 days, and adenosine triphosphate disodium in the sample after storage for 3 days was used. The content was quantified according to the determination method of disodium adenosine triphosphate described in Japanese Pharmacopoeia Standard 2002. And the content of the disodium adenosine triphosphate determined was evaluated as a relative value (residual rate (%)) when the content of the same compound at the start of storage was taken as 100%. The results are shown in Table 1.

[Reference Example 1]
A sample of Reference Example 1 was prepared by placing 10 mg of adenosine triphosphate disodium in a glass bottle.
[Reference Example 2]
Adenosine triphosphate disodium and dl-α-tocopherol calcium succinate were mixed in equal amounts, and 20 mg of the resulting mixture was placed in a glass bottle to give a sample of Reference Example 2.

[Comparative Examples 1 to 12]
Equivalent amounts of adenosine triphosphate disodium and each interactive component shown in Table 1 below (however, in Comparative Example 5 where the interactive component is cyanocobalamin, 1/100 amount of disodium adenosine triphosphate) ) After mixing, 20 mg of the resulting mixture (however, 10 mg for Comparative Example 5 in which the interactive component is cyanocobalamin) was placed in a glass bottle to obtain samples of Comparative Examples 1-12.

[Examples 1 to 12]
Equivalent amounts of disodium adenosine triphosphate and each interactive component shown in Table 1 below (however, in Example 5 where the interactive component is cyanocobalamin, 1/100 amount of disodium adenosine triphosphate) ) And mixing this mixture with an equal amount of dl-α-tocopherol calcium succinate with disodium adenosine triphosphate and 30 mg of the resulting mixture (provided that for Example 5 where the interactive component is cyanocobalamin) 20 mg) was put in a glass bottle and used as samples of Examples 1-12.

From the comparison between Reference Example 1 and Comparative Examples 1-12, adenosine triphosphate disodium and an interactive component were mixed and stored as compared with the case of storing adenosine triphosphate disodium alone. It became clear that the content of disodium triphosphate decreased. Further, from the comparison between Reference Example 1 and Reference Example 2, in comparison with the case of storing adenosine triphosphate disodium alone, adenosine triphosphate disodium and dl-α-tocopherol calcium succinate are mixed and stored. On the other hand, it was clarified that the content of adenosine triphosphate disodium was reduced. On the other hand, in comparison with Comparative Examples 1-12 and Examples 1-12, in addition to disodium adenosine triphosphate and an interactive component, Furthermore, it was clarified that, by further mixing and storing dl-α-tocopherol calcium succinate, a decrease in the content of disodium adenosine triphosphate was suppressed. In particular, the interactive components are benfotiamine (Example 2), riboflavin (Example 3), pyridoxine hydrochloride (Example 4), nicotinamide (Example 6), gamma-oryzanol (Example 10), anhydrous cafe In the case of In (Example 11), dl-α-tocopherol calcium succinate showed a remarkable content lowering inhibitory action.

  From the above test results, it has been clarified that dl-α-tocopherol calcium succinate has an action of suppressing a decrease in content of adenosine triphosphate disodium produced in the presence of each interactive component.

[Test Example 2] Examination of the inhibitory action of dl-α-tocopherol acetate in reducing the content of disodium adenosine triphosphate The dl-α-acetate acetate instead of dl-α-tocopherol calcium succinate used in Test Example 1 Using tocopherol, the stability (content reduction) of adenosine triphosphate disodium under high temperature conditions was confirmed.
Specifically, Comparative Example 13 and Examples 13 to 24 shown below were prepared, and the stability (content reduction) of adenosine triphosphate disodium was confirmed by the same method as in Test Example 1. did. The results are shown in Table 2.

[Comparative Example 13]
An equivalent amount of adenosine triphosphate disodium and fursultiamine hydrochloride was mixed, and 20 mg of the resulting mixture was placed in a glass bottle to give a sample of Comparative Example 13.
[Examples 13 to 24]
Equivalent amounts of disodium adenosine triphosphate and each interactive component shown in Table 2 below (however, in Example 17 where the interactive component is cyanocobalamin, 1/100 amount of disodium adenosine triphosphate) ) And admixing dl-α-tocopherol acetate with an equivalent amount of disodium adenosine triphosphate to this mixture, and 30 mg of the resulting mixture (provided that 20 mg for Example 17 where the interactive component is cyanocobalamin) Was put into a glass bottle and used as samples of Examples 13 to 24.

  From the comparison between Comparative Examples 2 to 13 and Examples 13 to 24, dl-α-tocopherol acetate was also used in the presence of an interactive component in the same manner as dl-α-tocopherol calcium succinate used in Test Example 1. It became clear that it has the effect | action which suppresses the content reduction of the produced adenosine triphosphate disodium. In particular, the interactive components are fursultiamine hydrochloride (Example 13), benfotiamine (Example 14), riboflavin (Example 15), pyridoxine hydrochloride (Example 16), cyanocobalamin (Example 17), nicotinic acid In the case of amide (Example 18), gamma-oryzanol (Example 22), anhydrous caffeine (Example 23), and arginine hydrochloride (Example 24), dl-α-tocopherol acetate suppresses a significant decrease in content. The effect was shown.

[Test Example 3] Examination of inhibitory effect of chondroitin sulfate sodium on adenosine triphosphate disodium content in place of dl-α-tocopherol calcium succinate used in Test Example 1 The stability (content reduction) of adenosine triphosphate disodium under high temperature conditions was confirmed using “chondroitin sulfate sodium” described in 1.
Specifically, Examples 25 to 31 shown below were prepared, and the stability (content reduction) of adenosine triphosphate disodium under high temperature conditions was confirmed by the same method as in Test Example 1. The results are shown in Table 3.

[Examples 25 to 31]
Equivalent amounts of adenosine triphosphate disodium and each interactive component shown in Table 3 below are mixed. To this mixture, chondroitin sulfate sodium is mixed with an equal amount of adenosine triphosphate disodium, and 30 mg of the resulting mixture is added. It put into the glass bottle and it was set as the sample of Examples 25-31.

  From the comparison of Comparative Examples 1-4, 9, 10, 13 and Examples 25-31, as with dl-α-tocopherol calcium succinate used in Test Example 1, sodium chondroitin sulfate is also an interactive component. It was clarified that it has the effect of suppressing the decrease in the content of adenosine triphosphate disodium produced in the coexistence. In particular, when the interactive components were thiamine nitrate (Example 25) and benfotiamine (Example 27), sodium chondroitin sulfate showed a remarkable content-decreasing action.

  From the results of the above Test Examples 1 to 3, one or more selected from the group consisting of tocopherols and chondroitin sulfates are composed of adenosine triphosphate and a salt thereof produced in the presence of each interactive component. It became clear that it has the effect | action which suppresses the content fall of 1 or more types chosen from a group.

Production Example 1
The tablet of the manufacture example 1 containing the following components per tablet was manufactured by the conventional method.
Adenosine triphosphate disodium 20mg
Benfotiamine 50mg
Cyanocobalamin 10μg
Calcium pantothenate 10mg
Oxoamidin powder 10mg
Gamma oryzanol 3mg
Dl-α-Tocopherol calcium succinate 20mg
Crystalline cellulose 89.3mg
Hydroxypropylcellulose 20mg
Crospovidone 40mg
Calcium silicate 5mg
Magnesium stearate 2.7mg

Production Example 2
A sugar-coated layer containing the following components per tablet was formed on the tablets obtained in Production Example 1 by a conventional method to produce the enteric-coated sugar-coated tablets of Production Example 2.
Refined white sugar 90mg
Methacrylic acid copolymer LD 12mg
Precipitated calcium carbonate 40mg
Talc 40mg
Arabic gum powder 8mg
Hypromellose 8mg
Titanium oxide 3mg
Triethyl citrate 2mg
Gelatin 6mg
Polyoxyethylene (105) Polyoxypropylene (5) Glycol 1mg
Carnauba wax

Production Example 3
The tablet of the manufacture example 3 containing the following components per tablet was manufactured by the conventional method.
Adenosine triphosphate disodium 10mg
Fursultiamine hydrochloride 18.2mg
Pyridoxine hydrochloride 3.3mg
Chondroitin sulfate sodium ester 133.3mg
Glucosamine hydrochloride 37.5mg
Hydroxypropylcellulose 20mg
Crospovidone 40mg
Calcium silicate 5mg
Magnesium stearate 2.7mg

Production Example 4
A sugar-coated layer containing the following components per tablet was formed on the tablets obtained in Production Example 3 by a conventional method to produce the enteric-coated sugar-coated tablets of Production Example 4.
Refined white sugar 90mg
Methacrylic acid copolymer LD 12mg
Precipitated calcium carbonate 40mg
Talc 40mg
Arabic gum powder 8mg
Hypromellose 8mg
Titanium oxide 3mg
Triethyl citrate 2mg
Gelatin 6mg
Polyoxyethylene (105) Polyoxypropylene (5) Glycol 1mg
Carnauba wax

  According to the present invention, it is possible to provide a composition or the like that can be suitably used as a vitamin-containing health medicine or vitamin main ingredient preparation, in which a decrease in the content of one or more selected from the group consisting of adenosine triphosphate and its salt is suppressed. Can be used in the pharmaceutical industry.

Claims (7)

One or more selected from the group consisting of adenosine triphosphate and a salt thereof;
One or more selected from the group consisting of vitamin B1, vitamin B2, vitamin B6, vitamin B12, nicotinic acid, pantothenic acid, vitamin C, processed garlic, gamma oryzanol, caffeine and arginine;
One or more stabilization methods selected from the group consisting of adenosine triphosphate and a salt thereof, wherein at least one selected from the group consisting of tocopherols and chondroitin sulfates is allowed to coexist.
However, the method of making it coexist as a composition of the following (1)-(22) is remove | excluded.
(1) In a daily dose, adenosine triphosphate disodium 60.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, succinic acid dl-α-tocopherol calcium 20.7 mg, sodium ascorbate 112.6 mg, 25.0 mg of nicotinamide, 12.0 mg of dried dried elephant (powder equivalent amount 300 mg), 30.0 mg of dried eagle extract (price equivalent to crude drug 240 mg), 50.0 mg arginine hydrochloride, 50% anhydrous caffeine. Tablets containing 0 mg, hydrogenated oil 30.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate 6.0 mg.
(2) In a daily dose, adenosine triphosphate disodium 120.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, gamma-oryzanol 10.0 mg, succinic acid dl-α -Tablets containing 103.6 mg of tocopherol calcium, 106.0 mg of D-mannitol, 120.1 mg of crystalline cellulose, 37.5 mg of hydroxypropylcellulose, 45.0 mg of carmellose calcium and 7.5 mg of magnesium stearate.
(3) In a daily dose, adenosine triphosphate disodium 120.0 mg, fursultiamine hydrochloride 100.0 mg, pyridoxine hydrochloride 100.0 mg, cyanocobalamin 1500 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103 .6 mg, tablets containing 30.0 mg calcium pantothenate, 60.0 mg hydrogenated oil, 181.1 mg crystalline cellulose, 32.4 mg hydroxypropylcellulose, 64.8 mg carmellose and 6.6 mg magnesium stearate.
(4) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (raw drug substance equivalent 600 mg) 60.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, Pyridoxine hydrochloride 10.0 mg, dl-α-tocopherol calcium succinate 20.7 mg, sodium ascorbate 112.6 mg, nicotinic acid amide 25.0 mg, dried prawn extract (powder equivalent amount 300 mg) 12.0 mg, dried ogi extract ( (Powder equivalent amount 240 mg) 30.0 mg, arginine hydrochloride 50.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 30.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate Contains 6.0 mg Tablets.
(5) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 120.0 mg, carrot dry extract (raw drug substance equivalent 600 mg) 60.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg , Pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103.6 mg, D-mannitol 106.0 mg, crystalline cellulose 120.1 mg, hydroxypropylcellulose 37.5 mg, carmellose A tablet containing 45.0 mg calcium and 7.5 mg magnesium stearate.
(6) In daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot extract (pure drug equivalent 1500 mg) 375.0 mg, d-α-tocopherol 300.0 mg, bisbenchamine A tablet containing 25.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, hydrogenated oil 60.0 mg, crystalline cellulose 264.8 mg, hydroxypropylcellulose 42.4 mg, carmellose 70.8 mg and magnesium stearate 12.0 mg.
(7) In a daily dose (3 tablets), 60.0 mg of adenosine 5′-triphosphate disodium, 60.0 mg of carrot dry extract (raw drug substance equivalent amount 600 mg), 100.0 mg of fursultiamine hydrochloride, pyridoxine hydrochloride 100 0.0 mg, 1500 mg of mecobalamin, 100.0 mg of d-α-tocopherol acetate, 5.0 mg of folic acid, 36.0 mg of hydrogenated oil, 107.5 mg of crystalline cellulose, 24.0 mg of hydroxypropylcellulose, 30.0 mg of carmellose calcium and magnesium stearate Tablet containing 6.0 mg.
(8) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (native drug substance 500 mg) 50.0 mg, licorice extract 250.0 mg, kukosi extract 12.0 mg, Garbage extract 10.0 mg, Sanshuyu extract 10.0 mg, Toshishi extract 6.0 mg, Yakuchi powder 100.0 mg, Ryutan powder 50.0 mg, Dehydrocholic acid 20.0 mg, Thiamine nitrate 10.0 mg, Riboflavin 10.0 mg, Cyanocobalamin 60 μg, Acetic acid Tablet containing tocopherol 10.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 72.0 mg, crystalline cellulose 165.0 mg, hydroxypropylcellulose 27.0 mg, carmellose 39.0 mg and magnesium stearate 9.0 mg.
(9) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (raw drug substance equivalent 1500 mg) 150.0 mg, dicetiamine hydrochloride 10.0 mg, riboflavin 6.0 mg, Pyridoxine hydrochloride 8.0 mg, d-α-tocopherol acetate 15.0 mg, ascorbic acid 150.0 mg, nicotinic acid amide 50.0 mg, retinol palmitate 2000 IU, cholecalciferol 200 IU, anhydrous calcium hydrogen phosphate 68.0 mg, hydrogenated oil A tablet containing 100.9 mg, crystalline cellulose 170.9 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 65.0 mg and magnesium stearate 7.5 mg.
(10) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (native drug substance 700 mg) 70.0 mg, chondroitin sodium sulfate 100.0 mg, royal jelly 200.0 mg , Liver hydrolyzate 50.0 mg, d-α-tocopherol acetate 100.0 mg, bisbenchamine 25.0 mg, cyanocobalamin 72.0 μg, hydrogenated oil 72.0 mg, crystalline cellulose 165.0 mg, hydroxypropylcellulose 27.0 mg, Tablet containing carmellose 82.0 mg and magnesium stearate 9.0 mg.
(11) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 50.0 mg, Ezokogi dry extract (powder equivalent amount 300 mg) 12.0 mg, dried ogi extract (raw) Herbal equivalent 240 mg) 30.0 mg, arginine hydrochloride 50.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, succinic acid dl-α-tocopherol calcium 20.7 mg, sodium ascorbate 112.6 mg Nicotinamide 25.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 40.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate 6.0 mg.
(12) In daily dose (3 tablets), adenosine 5′-triphosphate disodium 120.0 mg, oxoamidin powder 50.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60.0 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103.6 mg, D-mannitol 116.0 mg, crystalline cellulose 120.1 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 45.0 mg and stearin Tablets containing 7.5 mg of magnesium acid.
(13) In a daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 30.0 mg, fursultiamine hydrochloride 20.0 mg, chondroitin sulfate sodium 900.0 mg, D-mannitol 125 Tablets containing 0.0 mg, crystalline cellulose 130.0 mg, hydroxypropylcellulose 40.8 mg, carmellose calcium 61.2 mg and magnesium stearate 13.0 mg.
(14) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 20.0 mg, carrot extract (raw substance equivalent 600 mg) 180.0 mg, d-α-tocopherol acetate 10.0 mg, bisbenchamine 20.0 mg, riboflavin 10.0 mg, pyridoxine hydrochloride 20.0 mg, cyanocobalamin 20.0 μg, calcium pantothenate 20.0 mg, nicotinamide 20.0 mg, hydrogenated oil 36.0 mg, crystalline cellulose 144 Tablets containing 0.0 mg, hydroxypropylcellulose 24.0 mg, carmellose calcium 30.0 mg and magnesium stearate 6.0 mg.
(15) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 30.0 mg, fursultiamine hydrochloride 100.0 mg, pyridoxine hydrochloride 100.0 mg, mecobalamin 1500 μg, acetate d -Α-tocopherol 100.0 mg, hydrogenated oil 36.0 mg, 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 Film-coated tablet containing 12.3 mg, triethyl citrate 6.16 mg and titanium oxide 0.54 mg.
(16) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 20.0 mg, kokushi extract 60.0 mg, toshishi extract 3.0 mg, royal jelly 50.0 mg, dehydrocholic acid 10 0.0 mg, 10.0 mg riboflavin, 2.0 μg cyanocobalamin, 10.0 mg d-α-tocopherol acetate, 12.0 mg nicotinamide, 50.0 mg anhydrous caffeine, 36.0 mg hydrogenated oil, 93.0 mg D-mannitol, A tablet containing crystalline cellulose 120.0 mg, hydroxypropylcellulose 24.0 mg, carmellose 36.0 mg and magnesium stearate 6.0 mg.
(17) In a daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 200.0 mg, placenta extract 800.0 mg, thiamine nitrate 10.0 mg, d-α-tocopherol acetate 10 0.0 mg, carrot extract 60.0 mg, hydrogenated oil 64.0 mg, D-mannitol 120.0 mg, crystalline cellulose 155.0 mg, calcium silicate 48.0 mg, hydroxypropylcellulose 60.0 mg, carmellose calcium 84.0 mg and stearin Tablets containing 9.0 mg of magnesium acid.
(18) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 50.0 mg, arginine hydrochloride 50.0 mg, gamma-oryzanol 10.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, dl-α-tocopherol calcium succinate 20.7 mg, retinol palmitate 2000.0 IU, sodium ascorbate 112.6 mg, nicotinamide 25.0 mg, anhydrous caffeine 50.0 mg, Tablets containing hardened oil 100.9 mg, crystalline cellulose 165.6 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 65.0 mg and magnesium stearate 7.5 mg.
(19) In a daily dose, adenosine triphosphate disodium 120.0 mg, ubidecarenone 30.0 mg, acetic acid d-α-tocopherol 10.0 mg, nicotinamide 20.0 mg, riboflavin 6.0 mg, D-mannitol 325. A tablet containing 8 mg, crystalline cellulose 144.0 mg, carmellose calcium 36.0 mg, hydroxypropylcellulose 21.0 mg and magnesium stearate 7.2 mg.
(20) Purified water 53.0% by weight, sodium chondroitin sulfate 0.2% by weight, adenosine triphosphate 0.2% by weight, stearyl alcohol 1.0% by weight, formula (X-O-) n-A- ( in -O-R) m (where, a is shown glucose, R represents straight-chain or branched alkyl or alkenyl group having total carbon number of 18, m is 1, X is -CH ₂ COONa, n is 1) 1.0 wt% of a sugar derivative represented by the formula: sodium isostearate 0.5 wt%, glycerin 10.0 wt%, dipropylene glycol 5.0 wt%, stearic acid 1.0 wt%, L-arginine 1 wt%, squalane 10.0 wt%, jojoba oil 10.0 wt%, petrolatum 5.0 wt%, vitamin A palmitate 1.0 wt%, α-tocopherol 1.0 wt%, preservative 0.5 wt% % And fragrance 0.5 Emollient emulsions containing amount%.
(21) Dipropylene glycol 0.5% by mass, hydrogenated bisabolol 0.5% by mass, ethanol 60.0% by mass, isopropylmethylphenol 0.1% by mass, D-pantothenyl alcohol 0.2% by mass, adenosine 3 0.05% by mass of phosphoric acid, 0.05% by mass of hinokitiol, 0.05% by mass of tocopherol acetate, 0.001% by mass of cephalanthin, 0.6% by mass of polyoxyethylene (60) hydrogenated castor oil, coenzyme Q10 001% by mass, fragrance 0.05% by mass, litchi extract 0.1% by mass, spruce extract 0.1% by mass, loquat leaf extract 0.1% by mass, buckwheat extract 0.1% by mass, asparagus linen alice extract 1% by mass, 0.1% by weight of purple extract, 0.1% by weight of carrot extract, 0.05% dipotassium glycyrrhizinate A hair restorer comprising:% by weight, 0.0001% by mass of glycine, 0.0001% by mass of L-alanine, 0.0001% by mass of L-proline, 0.05% by mass of tetrasodium edetate, and the balance of purified water.
(22) 80% ethanol 50.0% by weight, pyridoxine dioctanoate 0.05% by weight, polyoxyethylene / polyoxypropylene alkyl ether 1.0% by weight, methyl paraben 0.1% by weight, vitamin E 0.01% by weight % Hair tonic containing 1% adenosine triphosphate monosodium 0.02%, flavoring 0.5% by weight and purified water balance. One or more selected from the group consisting of adenosine triphosphate and a salt thereof;
One or more selected from the group consisting of vitamin B1, vitamin B2, vitamin B6, vitamin B12, nicotinic acid, pantothenic acid, vitamin C, processed garlic, gamma oryzanol, caffeine and arginine;
The stabilization method according to claim 1, wherein one or more selected from the group consisting of tocopherols and chondroitin sulfates are contained in the same composition.   The stabilization method according to claim 2, wherein the composition is a solid composition. One or more selected from the group consisting of adenosine triphosphate and a salt thereof;
One or more selected from the group consisting of vitamin B1, vitamin B2, vitamin B6, vitamin B12, nicotinic acid, pantothenic acid, vitamin C, processed garlic, gamma oryzanol, caffeine and arginine;
One or more kinds selected from the group consisting of adenosine triphosphate and a salt thereof, wherein one or more kinds selected from the group consisting of tocopherols and chondroitin sulfates are contained in the same composition A method for producing a composition having an improved surface.
However, the manufacturing method of the composition of the following (1)-(22) is remove | excluded.
(1) In a daily dose, adenosine triphosphate disodium 60.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, succinic acid dl-α-tocopherol calcium 20.7 mg, sodium ascorbate 112.6 mg, 25.0 mg of nicotinamide, 12.0 mg of dried dried elephant (powder equivalent amount 300 mg), 30.0 mg of dried eagle extract (price equivalent to crude drug 240 mg), 50.0 mg arginine hydrochloride, 50% anhydrous caffeine. Tablets containing 0 mg, hydrogenated oil 30.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate 6.0 mg.
(2) In a daily dose, adenosine triphosphate disodium 120.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, gamma-oryzanol 10.0 mg, succinic acid dl-α -Tablets containing 103.6 mg of tocopherol calcium, 106.0 mg of D-mannitol, 120.1 mg of crystalline cellulose, 37.5 mg of hydroxypropylcellulose, 45.0 mg of carmellose calcium and 7.5 mg of magnesium stearate.
(3) In a daily dose, adenosine triphosphate disodium 120.0 mg, fursultiamine hydrochloride 100.0 mg, pyridoxine hydrochloride 100.0 mg, cyanocobalamin 1500 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103 .6 mg, tablets containing 30.0 mg calcium pantothenate, 60.0 mg hydrogenated oil, 181.1 mg crystalline cellulose, 32.4 mg hydroxypropylcellulose, 64.8 mg carmellose and 6.6 mg magnesium stearate.
(4) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (raw drug substance equivalent 600 mg) 60.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, Pyridoxine hydrochloride 10.0 mg, dl-α-tocopherol calcium succinate 20.7 mg, sodium ascorbate 112.6 mg, nicotinic acid amide 25.0 mg, dried prawn extract (powder equivalent amount 300 mg) 12.0 mg, dried ogi extract ( (Powder equivalent amount 240 mg) 30.0 mg, arginine hydrochloride 50.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 30.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate Contains 6.0 mg Tablets.
(5) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 120.0 mg, carrot dry extract (raw drug substance equivalent 600 mg) 60.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg , Pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103.6 mg, D-mannitol 106.0 mg, crystalline cellulose 120.1 mg, hydroxypropylcellulose 37.5 mg, carmellose A tablet containing 45.0 mg calcium and 7.5 mg magnesium stearate.
(6) In daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot extract (pure drug equivalent 1500 mg) 375.0 mg, d-α-tocopherol 300.0 mg, bisbenchamine A tablet containing 25.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, hydrogenated oil 60.0 mg, crystalline cellulose 264.8 mg, hydroxypropylcellulose 42.4 mg, carmellose 70.8 mg and magnesium stearate 12.0 mg.
(7) In a daily dose (3 tablets), 60.0 mg of adenosine 5′-triphosphate disodium, 60.0 mg of carrot dry extract (raw drug substance equivalent amount 600 mg), 100.0 mg of fursultiamine hydrochloride, pyridoxine hydrochloride 100 0.0 mg, 1500 mg of mecobalamin, 100.0 mg of d-α-tocopherol acetate, 5.0 mg of folic acid, 36.0 mg of hydrogenated oil, 107.5 mg of crystalline cellulose, 24.0 mg of hydroxypropylcellulose, 30.0 mg of carmellose calcium and magnesium stearate Tablet containing 6.0 mg.
(8) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (native drug substance 500 mg) 50.0 mg, licorice extract 250.0 mg, kukosi extract 12.0 mg, Garbage extract 10.0 mg, Sanshuyu extract 10.0 mg, Toshishi extract 6.0 mg, Yakuchi powder 100.0 mg, Ryutan powder 50.0 mg, Dehydrocholic acid 20.0 mg, Thiamine nitrate 10.0 mg, Riboflavin 10.0 mg, Cyanocobalamin 60 μg, Acetic acid Tablet containing tocopherol 10.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 72.0 mg, crystalline cellulose 165.0 mg, hydroxypropylcellulose 27.0 mg, carmellose 39.0 mg and magnesium stearate 9.0 mg.
(9) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (raw drug substance equivalent 1500 mg) 150.0 mg, dicetiamine hydrochloride 10.0 mg, riboflavin 6.0 mg, Pyridoxine hydrochloride 8.0 mg, d-α-tocopherol acetate 15.0 mg, ascorbic acid 150.0 mg, nicotinic acid amide 50.0 mg, retinol palmitate 2000 IU, cholecalciferol 200 IU, anhydrous calcium hydrogen phosphate 68.0 mg, hydrogenated oil A tablet containing 100.9 mg, crystalline cellulose 170.9 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 65.0 mg and magnesium stearate 7.5 mg.
(10) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (native drug substance 700 mg) 70.0 mg, chondroitin sodium sulfate 100.0 mg, royal jelly 200.0 mg , Liver hydrolyzate 50.0 mg, d-α-tocopherol acetate 100.0 mg, bisbenchamine 25.0 mg, cyanocobalamin 72.0 μg, hydrogenated oil 72.0 mg, crystalline cellulose 165.0 mg, hydroxypropylcellulose 27.0 mg, Tablet containing carmellose 82.0 mg and magnesium stearate 9.0 mg.
(11) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 50.0 mg, Ezokogi dry extract (powder equivalent amount 300 mg) 12.0 mg, dried ogi extract (raw) Herbal equivalent 240 mg) 30.0 mg, arginine hydrochloride 50.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, succinic acid dl-α-tocopherol calcium 20.7 mg, sodium ascorbate 112.6 mg Nicotinamide 25.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 40.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate 6.0 mg.
(12) In daily dose (3 tablets), adenosine 5′-triphosphate disodium 120.0 mg, oxoamidin powder 50.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60.0 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103.6 mg, D-mannitol 116.0 mg, crystalline cellulose 120.1 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 45.0 mg and stearin Tablets containing 7.5 mg of magnesium acid.
(13) In a daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 30.0 mg, fursultiamine hydrochloride 20.0 mg, chondroitin sulfate sodium 900.0 mg, D-mannitol 125 Tablets containing 0.0 mg, crystalline cellulose 130.0 mg, hydroxypropylcellulose 40.8 mg, carmellose calcium 61.2 mg and magnesium stearate 13.0 mg.
(14) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 20.0 mg, carrot extract (raw substance equivalent 600 mg) 180.0 mg, d-α-tocopherol acetate 10.0 mg, bisbenchamine 20.0 mg, riboflavin 10.0 mg, pyridoxine hydrochloride 20.0 mg, cyanocobalamin 20.0 μg, calcium pantothenate 20.0 mg, nicotinamide 20.0 mg, hydrogenated oil 36.0 mg, crystalline cellulose 144 Tablets containing 0.0 mg, hydroxypropylcellulose 24.0 mg, carmellose calcium 30.0 mg and magnesium stearate 6.0 mg.
(15) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 30.0 mg, fursultiamine hydrochloride 100.0 mg, pyridoxine hydrochloride 100.0 mg, mecobalamin 1500 μg, acetate d -Α-tocopherol 100.0 mg, hydrogenated oil 36.0 mg, 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 Film-coated tablet containing 12.3 mg, triethyl citrate 6.16 mg and titanium oxide 0.54 mg.
(16) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 20.0 mg, kokushi extract 60.0 mg, toshishi extract 3.0 mg, royal jelly 50.0 mg, dehydrocholic acid 10 0.0 mg, 10.0 mg riboflavin, 2.0 μg cyanocobalamin, 10.0 mg d-α-tocopherol acetate, 12.0 mg nicotinamide, 50.0 mg anhydrous caffeine, 36.0 mg hydrogenated oil, 93.0 mg D-mannitol, A tablet containing crystalline cellulose 120.0 mg, hydroxypropylcellulose 24.0 mg, carmellose 36.0 mg and magnesium stearate 6.0 mg.
(17) In a daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 200.0 mg, placenta extract 800.0 mg, thiamine nitrate 10.0 mg, d-α-tocopherol acetate 10 0.0 mg, carrot extract 60.0 mg, hydrogenated oil 64.0 mg, D-mannitol 120.0 mg, crystalline cellulose 155.0 mg, calcium silicate 48.0 mg, hydroxypropylcellulose 60.0 mg, carmellose calcium 84.0 mg and stearin Tablets containing 9.0 mg of magnesium acid.
(18) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 50.0 mg, arginine hydrochloride 50.0 mg, gamma-oryzanol 10.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, dl-α-tocopherol calcium succinate 20.7 mg, retinol palmitate 2000.0 IU, sodium ascorbate 112.6 mg, nicotinamide 25.0 mg, anhydrous caffeine 50.0 mg, Tablets containing hardened oil 100.9 mg, crystalline cellulose 165.6 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 65.0 mg and magnesium stearate 7.5 mg.
(19) In a daily dose, adenosine triphosphate disodium 120.0 mg, ubidecarenone 30.0 mg, acetic acid d-α-tocopherol 10.0 mg, nicotinamide 20.0 mg, riboflavin 6.0 mg, D-mannitol 325. A tablet containing 8 mg, crystalline cellulose 144.0 mg, carmellose calcium 36.0 mg, hydroxypropylcellulose 21.0 mg and magnesium stearate 7.2 mg.
(20) Purified water 53.0% by weight, sodium chondroitin sulfate 0.2% by weight, adenosine triphosphate 0.2% by weight, stearyl alcohol 1.0% by weight, formula (X-O-) n-A- ( in -O-R) m (where, a is shown glucose, R represents straight-chain or branched alkyl or alkenyl group having total carbon number of 18, m is 1, X is -CH ₂ COONa, n is 1) 1.0 wt% of a sugar derivative represented by the formula: sodium isostearate 0.5 wt%, glycerin 10.0 wt%, dipropylene glycol 5.0 wt%, stearic acid 1.0 wt%, L-arginine 1 wt%, squalane 10.0 wt%, jojoba oil 10.0 wt%, petrolatum 5.0 wt%, vitamin A palmitate 1.0 wt%, α-tocopherol 1.0 wt%, preservative 0.5 wt% % And fragrance 0.5 Emollient emulsions containing amount%.
(21) Dipropylene glycol 0.5% by mass, hydrogenated bisabolol 0.5% by mass, ethanol 60.0% by mass, isopropylmethylphenol 0.1% by mass, D-pantothenyl alcohol 0.2% by mass, adenosine 3 0.05% by mass of phosphoric acid, 0.05% by mass of hinokitiol, 0.05% by mass of tocopherol acetate, 0.001% by mass of cephalanthin, 0.6% by mass of polyoxyethylene (60) hydrogenated castor oil, coenzyme Q10 001% by mass, fragrance 0.05% by mass, litchi extract 0.1% by mass, spruce extract 0.1% by mass, loquat leaf extract 0.1% by mass, buckwheat extract 0.1% by mass, asparagus linen alice extract 1% by mass, 0.1% by weight of purple extract, 0.1% by weight of carrot extract, 0.05% dipotassium glycyrrhizinate A hair restorer comprising:% by weight, 0.0001% by mass of glycine, 0.0001% by mass of L-alanine, 0.0001% by mass of L-proline, 0.05% by mass of tetrasodium edetate, and the balance of purified water.
(22) 80% ethanol 50.0% by weight, pyridoxine dioctanoate 0.05% by weight, polyoxyethylene / polyoxypropylene alkyl ether 1.0% by weight, methyl paraben 0.1% by weight, vitamin E 0.01% by weight % Hair tonic containing 1% adenosine triphosphate monosodium 0.02%, flavoring 0.5% by weight and purified water balance.   The production method according to claim 4, wherein the composition is a solid composition. One or more selected from the group consisting of adenosine triphosphate and a salt thereof;
One or more selected from the group consisting of vitamin B1, vitamin B2, vitamin B6, vitamin B12, nicotinic acid, pantothenic acid, vitamin C, processed garlic, gamma oryzanol, caffeine and arginine;
A composition having improved stability of at least one selected from the group consisting of adenosine triphosphate and a salt thereof containing at least one selected from the group consisting of tocopherols and chondroitin sulfates.
However, the following compositions (1) to (22) are excluded.
(1) In a daily dose, adenosine triphosphate disodium 60.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, succinic acid dl-α-tocopherol calcium 20.7 mg, sodium ascorbate 112.6 mg, 25.0 mg of nicotinamide, 12.0 mg of dried dried elephant (powder equivalent amount 300 mg), 30.0 mg of dried eagle extract (price equivalent to crude drug 240 mg), 50.0 mg arginine hydrochloride, 50% anhydrous caffeine. Tablets containing 0 mg, hydrogenated oil 30.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate 6.0 mg.
(2) In a daily dose, adenosine triphosphate disodium 120.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, gamma-oryzanol 10.0 mg, succinic acid dl-α -Tablets containing 103.6 mg of tocopherol calcium, 106.0 mg of D-mannitol, 120.1 mg of crystalline cellulose, 37.5 mg of hydroxypropylcellulose, 45.0 mg of carmellose calcium and 7.5 mg of magnesium stearate.
(3) In a daily dose, adenosine triphosphate disodium 120.0 mg, fursultiamine hydrochloride 100.0 mg, pyridoxine hydrochloride 100.0 mg, cyanocobalamin 1500 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103 .6 mg, tablets containing 30.0 mg calcium pantothenate, 60.0 mg hydrogenated oil, 181.1 mg crystalline cellulose, 32.4 mg hydroxypropylcellulose, 64.8 mg carmellose and 6.6 mg magnesium stearate.
(4) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (raw drug substance equivalent 600 mg) 60.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, Pyridoxine hydrochloride 10.0 mg, dl-α-tocopherol calcium succinate 20.7 mg, sodium ascorbate 112.6 mg, nicotinic acid amide 25.0 mg, dried prawn extract (powder equivalent amount 300 mg) 12.0 mg, dried ogi extract ( (Powder equivalent amount 240 mg) 30.0 mg, arginine hydrochloride 50.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 30.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate Contains 6.0 mg Tablets.
(5) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 120.0 mg, carrot dry extract (raw drug substance equivalent 600 mg) 60.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg , Pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103.6 mg, D-mannitol 106.0 mg, crystalline cellulose 120.1 mg, hydroxypropylcellulose 37.5 mg, carmellose A tablet containing 45.0 mg calcium and 7.5 mg magnesium stearate.
(6) In daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot extract (pure drug equivalent 1500 mg) 375.0 mg, d-α-tocopherol 300.0 mg, bisbenchamine A tablet containing 25.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60 μg, hydrogenated oil 60.0 mg, crystalline cellulose 264.8 mg, hydroxypropylcellulose 42.4 mg, carmellose 70.8 mg and magnesium stearate 12.0 mg.
(7) In a daily dose (3 tablets), 60.0 mg of adenosine 5′-triphosphate disodium, 60.0 mg of carrot dry extract (raw drug substance equivalent amount 600 mg), 100.0 mg of fursultiamine hydrochloride, pyridoxine hydrochloride 100 0.0 mg, 1500 mg of mecobalamin, 100.0 mg of d-α-tocopherol acetate, 5.0 mg of folic acid, 36.0 mg of hydrogenated oil, 107.5 mg of crystalline cellulose, 24.0 mg of hydroxypropylcellulose, 30.0 mg of carmellose calcium and magnesium stearate Tablet containing 6.0 mg.
(8) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (native drug substance 500 mg) 50.0 mg, licorice extract 250.0 mg, kukosi extract 12.0 mg, Garbage extract 10.0 mg, Sanshuyu extract 10.0 mg, Toshishi extract 6.0 mg, Yakuchi powder 100.0 mg, Ryutan powder 50.0 mg, Dehydrocholic acid 20.0 mg, Thiamine nitrate 10.0 mg, Riboflavin 10.0 mg, Cyanocobalamin 60 μg, Acetic acid Tablet containing tocopherol 10.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 72.0 mg, crystalline cellulose 165.0 mg, hydroxypropylcellulose 27.0 mg, carmellose 39.0 mg and magnesium stearate 9.0 mg.
(9) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (raw drug substance equivalent 1500 mg) 150.0 mg, dicetiamine hydrochloride 10.0 mg, riboflavin 6.0 mg, Pyridoxine hydrochloride 8.0 mg, d-α-tocopherol acetate 15.0 mg, ascorbic acid 150.0 mg, nicotinic acid amide 50.0 mg, retinol palmitate 2000 IU, cholecalciferol 200 IU, anhydrous calcium hydrogen phosphate 68.0 mg, hydrogenated oil A tablet containing 100.9 mg, crystalline cellulose 170.9 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 65.0 mg and magnesium stearate 7.5 mg.
(10) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, carrot dry extract (native drug substance 700 mg) 70.0 mg, chondroitin sodium sulfate 100.0 mg, royal jelly 200.0 mg , Liver hydrolyzate 50.0 mg, d-α-tocopherol acetate 100.0 mg, bisbenchamine 25.0 mg, cyanocobalamin 72.0 μg, hydrogenated oil 72.0 mg, crystalline cellulose 165.0 mg, hydroxypropylcellulose 27.0 mg, Tablet containing carmellose 82.0 mg and magnesium stearate 9.0 mg.
(11) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 50.0 mg, Ezokogi dry extract (powder equivalent amount 300 mg) 12.0 mg, dried ogi extract (raw) Herbal equivalent 240 mg) 30.0 mg, arginine hydrochloride 50.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, succinic acid dl-α-tocopherol calcium 20.7 mg, sodium ascorbate 112.6 mg Nicotinamide 25.0 mg, anhydrous caffeine 50.0 mg, hydrogenated oil 40.0 mg, hydroxypropylcellulose 24.0 mg, crystalline cellulose 125.7 mg, carmellose 30.0 mg and magnesium stearate 6.0 mg.
(12) In daily dose (3 tablets), adenosine 5′-triphosphate disodium 120.0 mg, oxoamidin powder 50.0 mg, benfotiamine 138.3 mg, riboflavin 12.0 mg, pyridoxine hydrochloride 50.0 mg, cyanocobalamin 60.0 μg, gamma-oryzanol 10.0 mg, dl-α-tocopherol calcium succinate 103.6 mg, D-mannitol 116.0 mg, crystalline cellulose 120.1 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 45.0 mg and stearin Tablets containing 7.5 mg of magnesium acid.
(13) In a daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 30.0 mg, fursultiamine hydrochloride 20.0 mg, chondroitin sulfate sodium 900.0 mg, D-mannitol 125 Tablets containing 0.0 mg, crystalline cellulose 130.0 mg, hydroxypropylcellulose 40.8 mg, carmellose calcium 61.2 mg and magnesium stearate 13.0 mg.
(14) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 20.0 mg, carrot extract (raw substance equivalent 600 mg) 180.0 mg, d-α-tocopherol acetate 10.0 mg, bisbenchamine 20.0 mg, riboflavin 10.0 mg, pyridoxine hydrochloride 20.0 mg, cyanocobalamin 20.0 μg, calcium pantothenate 20.0 mg, nicotinamide 20.0 mg, hydrogenated oil 36.0 mg, crystalline cellulose 144 Tablets containing 0.0 mg, hydroxypropylcellulose 24.0 mg, carmellose calcium 30.0 mg and magnesium stearate 6.0 mg.
(15) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 30.0 mg, fursultiamine hydrochloride 100.0 mg, pyridoxine hydrochloride 100.0 mg, mecobalamin 1500 μg, acetate d -Α-tocopherol 100.0 mg, hydrogenated oil 36.0 mg, 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 Film-coated tablet containing 12.3 mg, triethyl citrate 6.16 mg and titanium oxide 0.54 mg.
(16) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 20.0 mg, kokushi extract 60.0 mg, toshishi extract 3.0 mg, royal jelly 50.0 mg, dehydrocholic acid 10 0.0 mg, 10.0 mg riboflavin, 2.0 μg cyanocobalamin, 10.0 mg d-α-tocopherol acetate, 12.0 mg nicotinamide, 50.0 mg anhydrous caffeine, 36.0 mg hydrogenated oil, 93.0 mg D-mannitol, A tablet containing crystalline cellulose 120.0 mg, hydroxypropylcellulose 24.0 mg, carmellose 36.0 mg and magnesium stearate 6.0 mg.
(17) In a daily dose (6 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 200.0 mg, placenta extract 800.0 mg, thiamine nitrate 10.0 mg, d-α-tocopherol acetate 10 0.0 mg, carrot extract 60.0 mg, hydrogenated oil 64.0 mg, D-mannitol 120.0 mg, crystalline cellulose 155.0 mg, calcium silicate 48.0 mg, hydroxypropylcellulose 60.0 mg, carmellose calcium 84.0 mg and stearin Tablets containing 9.0 mg of magnesium acid.
(18) In a daily dose (3 tablets), adenosine 5′-triphosphate disodium 60.0 mg, oxoamidin powder 50.0 mg, arginine hydrochloride 50.0 mg, gamma-oryzanol 10.0 mg, thiamine nitrate 10.0 mg, riboflavin 4.0 mg, pyridoxine hydrochloride 10.0 mg, dl-α-tocopherol calcium succinate 20.7 mg, retinol palmitate 2000.0 IU, sodium ascorbate 112.6 mg, nicotinamide 25.0 mg, anhydrous caffeine 50.0 mg, Tablets containing hardened oil 100.9 mg, crystalline cellulose 165.6 mg, hydroxypropylcellulose 37.5 mg, carmellose calcium 65.0 mg and magnesium stearate 7.5 mg.
(19) In a daily dose, adenosine triphosphate disodium 120.0 mg, ubidecarenone 30.0 mg, acetic acid d-α-tocopherol 10.0 mg, nicotinamide 20.0 mg, riboflavin 6.0 mg, D-mannitol 325. A tablet containing 8 mg, crystalline cellulose 144.0 mg, carmellose calcium 36.0 mg, hydroxypropylcellulose 21.0 mg and magnesium stearate 7.2 mg.
(20) Purified water 53.0% by weight, sodium chondroitin sulfate 0.2% by weight, adenosine triphosphate 0.2% by weight, stearyl alcohol 1.0% by weight, formula (X-O-) n-A- ( in -O-R) m (where, a is shown glucose, R represents straight-chain or branched alkyl or alkenyl group having total carbon number of 18, m is 1, X is -CH ₂ COONa, n is 1) 1.0 wt% of a sugar derivative represented by the formula: sodium isostearate 0.5 wt%, glycerin 10.0 wt%, dipropylene glycol 5.0 wt%, stearic acid 1.0 wt%, L-arginine 1 wt%, squalane 10.0 wt%, jojoba oil 10.0 wt%, petrolatum 5.0 wt%, vitamin A palmitate 1.0 wt%, α-tocopherol 1.0 wt%, preservative 0.5 wt% % And fragrance 0.5 Emollient emulsions containing amount%.
(21) Dipropylene glycol 0.5% by mass, hydrogenated bisabolol 0.5% by mass, ethanol 60.0% by mass, isopropylmethylphenol 0.1% by mass, D-pantothenyl alcohol 0.2% by mass, adenosine 3 0.05% by mass of phosphoric acid, 0.05% by mass of hinokitiol, 0.05% by mass of tocopherol acetate, 0.001% by mass of cephalanthin, 0.6% by mass of polyoxyethylene (60) hydrogenated castor oil, coenzyme Q10 001% by mass, fragrance 0.05% by mass, litchi extract 0.1% by mass, spruce extract 0.1% by mass, loquat leaf extract 0.1% by mass, buckwheat extract 0.1% by mass, asparagus linen alice extract 1% by mass, 0.1% by weight of purple extract, 0.1% by weight of carrot extract, 0.05% dipotassium glycyrrhizinate A hair restorer comprising:% by weight, 0.0001% by mass of glycine, 0.0001% by mass of L-alanine, 0.0001% by mass of L-proline, 0.05% by mass of tetrasodium edetate, and the balance of purified water.
(22) 80% ethanol 50.0% by weight, pyridoxine dioctanoate 0.05% by weight, polyoxyethylene / polyoxypropylene alkyl ether 1.0% by weight, methyl paraben 0.1% by weight, vitamin E 0.01% by weight % Hair tonic containing 1% adenosine triphosphate monosodium 0.02%, flavoring 0.5% by weight and purified water balance.   The composition according to claim 6, which is solid.