JP6055180B2 - Composition - Google Patents

Description

  The present invention relates to a composition having improved stability of 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.
Adenosine triphosphate or its salts have various pharmacological actions, such as improvement of various symptoms associated with sequelae of head trauma, stabilization of regulatory function in heart failure, regulatory eye strain, and chronic deterioration of gastrointestinal function. In addition to being used as an active ingredient of pharmaceuticals used for vertigo based on gastritis, Meniere's disease and inner ear disorders, it is also known to increase muscle torque and reduce muscle fatigue (Patent Document 1). It is a highly useful component.

However, adenosine triphosphate or a salt thereof is unstable in a humid environment, a low pH environment, or a high temperature environment, and in a composition containing adenosine triphosphate or a salt thereof, a decrease in content over time is a problem. It becomes. Such a decrease in content causes a decrease in the uniformity of the composition and the like, which in turn degrades the quality of the composition and the like, thereby reducing its commercial value.
And the stabilization method corresponding to each destabilization factor is known with respect to the instability in the above-mentioned environment. Specifically, for humid environments, means for storing the composition together with a desiccant such as silica gel, for low pH environments, means for coating the composition with an acid resistant (enteric) coating agent, high temperature For the environment, means for refrigerated storage of the composition are known. However, a means that can be stabilized more simply than these has been demanded.

JP-T-2004-535417 International Publication No. 2008/001494 Pamphlet International Publication No. 2006/126663 Pamphlet

  An object of the present invention is to provide a composition 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 and stability is improved.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have added one or more selected from the group consisting of adenosine triphosphate and its salt to one or more selected from the group consisting of aspartic acid and its salt. It has been found that the coexistence suppresses a decrease in content under one or more high-temperature conditions selected from the group consisting of adenosine triphosphate and a salt thereof, and improves stability.

  That is, the present invention provides a composition containing one or more members selected from the group consisting of aspartic acid and salts thereof, and one or more members selected from the group consisting of adenosine triphosphate and salts thereof.

  Further, the present invention is characterized in that one or more selected from the group consisting of adenosine triphosphate and a salt thereof and one or more selected from the group consisting of aspartic acid and a salt thereof coexist. One or more stabilization methods selected from the group consisting of phosphoric acid and salts thereof are provided.

According to the present invention, one or more kinds selected from the group consisting of adenosine triphosphate and a salt thereof can be easily suppressed from decreasing in content with time, and have improved stability and improved quality. Can be provided.
In addition, according to the stabilization method of the present invention, it is possible to easily suppress a decrease in the content of one or more selected from the group consisting of adenosine triphosphate and a salt thereof, to improve stability, and to improve adenosine triphosphate. And the commercial value of a composition containing one or more selected from the group consisting of the salts thereof.

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

In the present invention, “aspartic acid” may be either L-aspartic acid or D-aspartic acid, or a mixture thereof. Among these, L-aspartic acid is preferable.
In the present invention, examples of the “aspartic acid salt” include alkali metal salts such as sodium salt and potassium salt of the above “aspartic acid”; alkaline earth metal salts such as magnesium salt and calcium salt, and the like. It can be used alone or in combination of two or more. Of these, magnesium salts, potassium salts, sodium salts, and calcium salts are preferable, and magnesium salts and potassium salts are more preferable.

In the present invention, “one or more selected from the group consisting of aspartic acid and salts thereof” includes aspartic acid free form, aspartic acid potassium salt, aspartic acid sodium salt, aspartic acid calcium salt and aspartic acid. One or more members selected from the group consisting of magnesium salts are preferred, and one or more members selected from the group consisting of potassium salts of aspartic acid and magnesium salts of aspartic acid are more preferable.
In addition, these aspartic acid and its salt are well-known compounds, A commercially available thing may be used and it is also possible to manufacture by a well-known method.

The content of one or more selected from the group consisting of aspartic acid and a salt thereof in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use and the like of the composition. For example, in the case of a composition for oral administration, a total of one or more selected from the group consisting of aspartic acid and its salt per day is about 1 to 4000 mg, more preferably about 5 to 800 mg, particularly preferably 10 to 10 mg. An amount that can be taken about 400 mg can be included.
In the present invention, it is preferable that one or more selected from the group consisting of aspartic acid and a salt thereof is contained in a total amount of 0.5 to 80% by mass with respect to the total mass of the composition, and 1 to 75% by mass Is more preferable, and it is especially preferable to contain 1.5-50 mass%.

In the present invention, “one or more selected from the group consisting of adenosine triphosphate and a salt thereof” 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 may 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.

The content of one or more selected from the group consisting of adenosine triphosphate and a salt thereof in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. . 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 present invention, it is preferable to contain one or more selected from the group consisting of adenosine triphosphate and a salt thereof in a total of 0.01 to 80% by mass relative to the total mass of the composition, and 0.05 to 60% by mass. It is more preferable to contain, and it is especially preferable to contain 1-50 mass%.
Further, the content mass ratio of one or more selected from the group consisting of aspartic acid and its salt in the composition of the present invention and one or more selected from the group consisting of adenosine triphosphate and its salt are not particularly limited, From the viewpoint of at least one stabilizing action selected from the group consisting of adenosine triphosphate and a salt thereof, adenosine triphosphate is used for a total of 1 part by mass selected from the group consisting of aspartic acid and a salt thereof. And a total of at least one selected from the group consisting of salts thereof is preferably 0.0008 to 1000 parts by mass, more preferably 0.015 to 150 parts by mass, and particularly preferably 0.05 to 36 parts by mass.

The composition of the present invention further contains a processed garlic in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt. You may squeeze it. A combination of at least one selected from the group consisting of adenosine triphosphate and its salt and a processed garlic product has an excellent preventive and / or recovery action against physical fatigue and / or mental fatigue (patent) On the other hand, the processed garlic product is unstable, and the generation of an unpleasant smell peculiar to garlic with the passage of time has been a problem. However, as described in Test Example 2 below, it has been clarified that at least one selected from the group consisting of aspartic acid and salts thereof has an action of suppressing odors derived from processed garlic.
Therefore, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, the garlic processed product of the present invention is further included. The composition is excellent in stability of at least one selected from the group consisting of adenosine triphosphate and a salt thereof, and stability of processed garlic, and is a pharmaceutical for preventing and / or recovering physical fatigue and / or mental fatigue. It is useful as a composition that can be used as:

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. Of these garlic processed products, oxoamidin (registered trademark), oxoamidin (registered trademark) powder, and oxoresin (registered trademark) powder are preferable.

  The shape of the composition of the present invention is not particularly limited, but the composition of the present invention is selected from the group consisting of one or more selected from the group consisting of aspartic acid and its salt, and the group consisting of adenosine triphosphate and its salt. In the case of an embodiment containing at least a processed garlic in addition to one or more, it is preferably a solid composition. As described in Test Example 2 below, at least one selected from the group consisting of aspartic acid and its salt is a solid composition such as a solid preparation in which the odor derived from the processed garlic is particularly problematic. It has an excellent effect of suppressing the odor of origin.

  The content of the processed garlic that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. 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 this invention, it is preferable to contain 0.1-70 mass% of garlic processed products with respect to the composition total mass, it is more preferable to contain 0.5-50 mass%, and it contains 1-30 mass%. Is particularly preferred.
Further, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof in the composition of the present invention and the processed garlic product is not particularly limited, but the action of suppressing odor derived from the processed garlic product and eyestrain From the viewpoint of the recovery action, 0.001 to 500 parts by mass of the garlic product is preferable, and 0.01 to 100 parts by mass is more preferable with respect to a total of 1 part by mass selected from the group consisting of aspartic acid and its salt. 0.05 to 50 parts by mass is particularly preferable.

In addition, the composition of the present invention includes one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, and also a vitamin B group May be included. The combination of one or more selected from the group consisting of adenosine triphosphate and salts thereof and the vitamin B group (particularly the vitamin B group selected from vitamin B1, vitamin B2, vitamin B6 and vitamin B12) is a combination of physical fatigue and / or mental Although it has an excellent recovery action against fatigue (see Patent Document 3), on the other hand, the vitamin B group is unstable, and content reduction with the passage of time has been a problem. . However, as described in Test Example 3 below, it has been clarified that one or more selected from the group consisting of aspartic acid and salts thereof have an action of suppressing a decrease in the content of vitamin B group.
Therefore, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, the present invention further comprises a vitamin B group. The composition is excellent in stability of at least one selected from the group consisting of adenosine triphosphate and a salt thereof and stability of vitamin B group, and can be used as a medicament for recovery from physical fatigue and / or mental fatigue. Useful as a composition.

  Examples of the “vitamin B group” include vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9 and vitamin B12, and these may be used alone or in combination of two or more. Can do. Among these, at least one selected from the group consisting of vitamin B1, vitamin B2, vitamin B6 and vitamin B12 is preferred, and two or more selected from the group consisting of vitamin B1, vitamin B2, vitamin B6 and vitamin B12 It is more preferable that it is at least three selected from the group consisting of vitamin B1, vitamin B2, vitamin B6 and vitamin B12, and a combination of vitamin B1, vitamin B2, vitamin B6 and vitamin B12 is particularly preferable. . As will be apparent from Test Example 3 below, among the above vitamin B groups, vitamin B12 has a problem in content stability, and the present inventors selected from the group consisting of aspartic acid and its salts. It has been found that one or more selected from the above can significantly suppress the decrease in the content of vitamin B12.

  The content of the vitamin B group that can be arbitrarily blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, the vitamin B group is contained in an amount that can be taken about 0.0001 to 3500 mg, more preferably about 0.001 to 1000 mg, particularly preferably about 0.005 to 500 mg per day. It can be shown.

In this invention, it is preferable to contain 0.000001-95 mass% of vitamin B groups with respect to the composition total mass, it is more preferable to contain 0.00001-80 mass%, 0.0001-60 mass% It is particularly preferable to contain it.
In addition, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof in the composition of the present invention and the vitamin B group is not particularly limited, but the action of suppressing a decrease in the content of the vitamin B group and eyestrain From the viewpoint of recovery action, 0.00000005 to 3000 parts by mass of vitamin B group is preferable, and 0.0000005 to 300 parts by mass is more preferable with respect to 1 part in total of at least one selected from the group consisting of aspartic acid and salts thereof. Preferably, 0.000005-100 mass parts is especially preferable.

In the present invention, “vitamin B1” includes thiamine itself and its derivatives (bisthiamine, thiamine disulfide, discetiamine, fursultiamine, octothiamine, chicotiamine, bisivethiamine, bisbenchamine, prosultiamine, benfotiamine. , Thiamine diphosphate and the like) and salts thereof (inorganic acid salts such as nitrates, hydrochlorides and sulfates) are also included, and these can be used alone or in combination of two or more.
In the present invention, thiamine hydrochloride, thiamine nitrate, bistiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salt, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, chicotiamine, bisibutamine, bisbenchamine, fursultiamine, pro One or more members selected from the group consisting of sultiamine and benfotiamine are preferable, and thiamine nitrate and benfotiamine are particularly preferable. These vitamin B1s are known compounds, and commercially available products may be used, or they can be produced by known methods.

  The content of vitamin B1 that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, the amount of vitamin B1 that can be taken per day is about 0.1 to 1000 mg, more preferably about 0.5 to 300 mg, and particularly preferably about 1 to 200 mg. it can.

In this invention, it is preferable to contain 0.005-60 mass% of vitamin B1 with respect to the composition total mass, It is more preferable to contain 0.01-40 mass%, 0.05-30 mass% containing It is particularly preferable to do this.
In addition, the mass ratio of vitamin B1 and at least one selected from the group consisting of aspartic acid and salts thereof in the composition of the present invention is not particularly limited, but the action of suppressing the decrease in vitamin B1 content and the action of restoring eye strain In view of the above, 0.00005 to 500 parts by mass of vitamin B1 is preferable, more preferably 0.0005 to 100 parts by mass, more preferably 1 part by mass of one or more selected from the group consisting of aspartic acid and salts thereof. 0.001 to 50 parts by mass is particularly preferable.

  In the present invention, “vitamin B2” includes, in addition to riboflavin itself, derivatives thereof (such as riboflavin phosphate, riboflavin butyrate and flavin adenine dinucleotide) and salts thereof (such as alkali metal salts such as sodium salt). In this invention, these can be used individually or in combination of 2 or more types. In the present invention, one or more selected from the group consisting of sodium flavin adenine dinucleotide, riboflavin, sodium riboflavin phosphate and riboflavin butyrate is preferable, and riboflavin is particularly preferable. These vitamin B2 are known compounds, and commercially available products may be used, or they can be produced by known methods.

  The content of vitamin B2 that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use and the like of the composition. For example, in the case of a composition for oral administration, the amount of vitamin B2 that can be taken per day is about 0.1 to 450 mg, more preferably about 0.5 to 100 mg, and particularly preferably about 1 to 50 mg. it can.

In this invention, it is preferable to contain 0.005-40 mass% of vitamin B2 with respect to the composition total mass, It is more preferable to contain 0.01-30 mass%, 0.05-20 mass% containing It is particularly preferable to do this.
Further, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof and vitamin B2 in the composition of the present invention is not particularly limited, but the action of suppressing the decrease in vitamin B2 content and the action of restoring eye strain In view of this, 0.00005 to 200 parts by mass of vitamin B2 is preferable, more preferably 0.0005 to 50 parts by mass, and more preferably 0 to 50 parts by mass with respect to a total of 1 part by mass selected from the group consisting of aspartic acid and salts thereof. 0.001 to 25 parts by mass is particularly preferable.

  In the present invention, “vitamin B3” includes 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. In the present invention, at least one selected from the group consisting of nicotinic acid, nicotinic acid amide and hepronicart is preferable. These vitamin B3 are known compounds, commercially available ones may be used, and they can be produced by known methods.

  The content of vitamin B3 that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, the amount of vitamin B3 that can be taken per day is about 1 to 600 mg, more preferably about 5 to 150 mg, and particularly preferably about 10 to 100 mg.

In this invention, it is preferable to contain vitamin B3 0.05-40 mass% with respect to the composition total mass, It is more preferable to contain 0.1-30 mass%, 0.5-20 mass% containing It is particularly preferable to do this.
In addition, the mass ratio of vitamin B3 and at least one selected from the group consisting of aspartic acid and its salt in the composition of the present invention is not particularly limited, but the action of suppressing the decrease in vitamin B3 content and the action of restoring eye strain In view of the above, 0.0005 to 200 parts by mass of vitamin B3 is preferable, 0.005 to 100 parts by mass is more preferable, and 0 to 100 parts by mass is more preferable for 1 or more kinds in total selected from the group consisting of aspartic acid and salts thereof. 0.01 to 50 parts by mass is particularly preferable.

  In the present invention, “vitamin B5” includes pantothenic acid itself, derivatives thereof (panthenol, panthetin, pantethein, coenzyme A, etc.) 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. 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 vitamin B5 are known compounds, and commercially available products may be used, or they can be produced by known methods.

  The content of vitamin B5 that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, vitamin B5 per day may be contained in an amount of about 0.5 to 300 mg, more preferably about 2.5 to 100 mg, particularly preferably about 5 to 50 mg. it can.

In this invention, it is preferable to contain 0.01-50 mass% of vitamin B5 with respect to the composition total mass, It is more preferable to contain 0.05-30 mass%, 0.1-15 mass% containing It is particularly preferable to do this.
Further, the mass ratio of vitamin B5 and at least one selected from the group consisting of aspartic acid and salts thereof in the composition of the present invention is not particularly limited, but the action of suppressing the decrease in vitamin B5 content and the action of restoring eye strain In view of this, vitamin B5 is preferably 0.0001 to 200 parts by mass, more preferably 0.001 to 50 parts by mass, more preferably 1 to 1 part by mass in total of at least one selected from the group consisting of aspartic acid and salts thereof. 0.01 to 25 parts 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 acids such as hydrochlorides). Salt, etc.) are also included, and in the present invention, these may be used alone or in combination of two or more. 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 B6 are known compounds, and commercially available products may be used, or they can be produced by known methods.

  The content of vitamin B6 that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, vitamin B6 per day may be contained in an amount of about 0.5 to 1000 mg, more preferably about 1 to 500 mg, particularly preferably about 2.5 to 100 mg. it can.

In this invention, it is preferable to contain 0.01-90 mass% of vitamin B6 with respect to a composition total mass, It is more preferable to contain 0.05-70 mass%, 0.1-40 mass% containing It is particularly preferable to do this.
Further, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof in the composition of the present invention and vitamin B6 is not particularly limited, but the action of suppressing the decrease in vitamin B6 content and the action of restoring eye strain In view of this, 0.001 to 1000 parts by mass of vitamin B6 is preferable, 0.0005 to 300 parts by mass is more preferable, and 0 to 300 parts by mass with respect to a total of 1 part by mass selected from the group consisting of aspartic acid and salts thereof. 0.001 to 50 parts by mass is particularly preferable.

  In the present invention, “vitamin B7” includes not only biotin itself but also a salt thereof (alkali metal salt such as sodium salt). These vitamin B7 are known compounds, and commercially available products may be used, or they can be produced by known methods.

  The content of vitamin B7 that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, the amount of vitamin B7 that can be taken per day is about 1 to 5000 μg, more preferably about 5 to 1000 μg, and particularly preferably about 10 to 500 μg.

In the present invention, vitamin B7 is preferably contained in an amount of 0.000001 to 1% by mass, more preferably 0.0001 to 0.5% by mass, and more preferably 0.0005 to 0. It is particularly preferable to contain 1% by mass.
Further, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof and vitamin B7 in the composition of the present invention is not particularly limited, but the action of suppressing the decrease in vitamin B7 content and the action of restoring eye strain In view of the above, Vitamin B7 0.00000005 to 10 parts by mass is preferable, 0.000001 to 5 parts by mass is more preferable, with respect to 1 part in total of at least one selected from the group consisting of aspartic acid and salts thereof. 0.0001-1 part by mass is particularly preferred.

  In the present invention, “vitamin B9” includes not only folic acid itself but also derivatives thereof (dihydrofolic acid, tetrahydrofolic acid, etc.) and salts thereof. In the present invention, folic acid is preferred. These vitamin B9s are known compounds, and commercially available products may be used, and they can be produced by known methods.

  The content of vitamin B9 that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, vitamin B9 is contained in an amount that can be taken about 0.05 to 50 mg, more preferably about 0.25 to 10 mg, particularly preferably about 0.5 to 5 mg per day. be able to.

In this invention, it is preferable to contain 0.001-20 mass% of vitamin B9 with respect to the composition total mass, It is more preferable to contain 0.005-5 mass%, 0.01-2.5 mass % Content is particularly preferable.
In addition, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof and vitamin B9 in the composition of the present invention is not particularly limited, but the action of suppressing the decrease in vitamin B9 content and the action of restoring eye strain In view of the above, 0.00005 to 100 parts by mass of vitamin B9 is preferable, 0.00001 to 10 parts by mass is more preferable, and 0 to 10 parts by mass with respect to a total of 1 part by mass selected from the group consisting of aspartic acid and salts thereof. 0.0001-5 parts 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 acids such as acetate) Salt, etc.) are also included, and in the present invention, these may be used alone or in combination of two or more. In the present invention, at least one member selected from the group consisting of hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, mecobalamin and hydroxocobalamin is preferable, and cyanocobalamin is particularly preferable. These vitamin B12 are known compounds, and commercially available products may be used, or they can be produced by known methods.

  The content of vitamin B12 that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, vitamin B12 per day is about 0.0001 to 50 mg, preferably about 0.00025 to 50 mg, more preferably about 0.0005 to 10 mg, and further preferably about 0.005. About 005 to 10 mg, even more preferably about 0.001 to 5 mg, and particularly preferably about 0.01 to 5 mg can be contained.

In the present invention, vitamin B12 is preferably contained in an amount of 0.00005 to 2 mass%, more preferably 0.0001 to 1 mass%, more preferably 0.0005 to 0.5 mass% relative to the total mass of the composition. % Content is particularly preferable.
In addition, the mass ratio of vitamin B12 and at least one selected from the group consisting of aspartic acid and salts thereof in the composition of the present invention is not particularly limited, but the action of suppressing the decrease in vitamin B12 content and the action of restoring eye strain In view of the above, Vitamin B12 is preferably 0.0000005 to 5 parts by mass, more preferably 0.000005 to 5 parts by mass with respect to 1 part by mass in total of at least one selected from the group consisting of aspartic acid and salts thereof. 0.0001-1 part by mass is particularly preferred.

In addition to the composition of the present invention, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, vitamin E is further added. You may contain. Vitamin E is unstable, and content reduction with the passage of time has been a problem. However, as described in Test Example 3 below, it has been clarified that at least one selected from the group consisting of aspartic acid and salts thereof has an action of suppressing a decrease in vitamin E content.
Therefore, in addition to at least one selected from the group consisting of aspartic acid and its salt, and at least one selected from the group consisting of adenosine triphosphate and its salt, the composition of the present invention further contains vitamin E. In addition to the stability of one or more selected from the group consisting of adenosine triphosphate and its salt, the product is also excellent in the stability of vitamin E, so the action of vitamin E (for example, shoulder / neck streak in peripheral blood circulation disorders) It is useful as a composition that can be used as a medicine that utilizes a variety of symptoms such as rest, numbness / coldness of hands and feet, and symptom relief.

  In the present invention, “vitamin E” includes 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. In the present invention, d-α-tocopherol succinate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, d-α-tocopherol acetate, dl-α-tocopherol acetate, d-α-tocopherol, One or more selected from the group consisting of dl-α-tocopherol and dl-α-tocopherol nicotinate is preferred, and dl-α-tocopherol calcium succinate is particularly preferred. These vitamin E are known compounds, and commercially available products may be used, or they can be produced by known methods.

  The content of vitamin E that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use, etc. of the composition. For example, in the case of a composition for oral administration, the amount of vitamin E that can be taken per day is about 1 to 3000 mg, more preferably about 2 to 600 mg, and particularly preferably about 5 to 300 mg.

In this invention, it is preferable to contain 0.01-90 mass% of vitamin E with respect to the composition total mass, It is more preferable to contain 0.05-70 mass%, 0.1-50 mass% containing It is particularly preferable to do this.
In addition, the mass ratio of vitamin E and at least one selected from the group consisting of aspartic acid and salts thereof in the composition of the present invention is not particularly limited, but aspartic acid from the viewpoint of the inhibitory effect on the decrease in vitamin E content. And 0.001 to 1000 parts by mass of vitamin E, more preferably 0.001 to 200 parts by mass, and 0.01 to 100 parts by mass with respect to a total of 1 part by mass of at least one selected from the group consisting of salts thereof. Particularly preferred.

In addition to the composition of the present invention, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, gamma oryzanol is further added. You may contain. Gamma-oryzanol is unstable, and the content reduction with the passage of time has been a problem. However, as described in Test Example 3 below, it has been clarified that one or more selected from the group consisting of aspartic acid and salts thereof have an action of suppressing a decrease in the content of gamma oryzanol.
Therefore, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, the composition of the present invention further contains gamma-oryzanol. In addition to the stability of one or more selected from the group consisting of adenosine triphosphate and its salt, the product is also excellent in the stability of gamma-oryzanol, so the action of gamma-oryzanol (for example, sebum secretion promoting action, blood flow It is useful as a composition that can be used as a medicine utilizing an improving action, a skin temperature raising action, an antioxidant action, an ultraviolet ray absorbing action, a tyrosinase activity inhibiting action, and the like.

  “Gamma-Oryzanol” is obtained from the seed coat of rice (Oryza sativa L.), 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.

  The content of gamma-oryzanol that can be optionally blended in the composition of the present invention is not particularly limited, and can be appropriately selected according to the administration method, shape, purpose of use and the like of the composition. For example, in the case of a composition for oral administration, 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 present invention, it is preferable to contain 0.01 to 30% by mass of gamma oryzanol with respect to the total mass of the composition, more preferably 0.05 to 20% by mass, and 0.1 to 10% by mass. It is particularly preferable to do this.
Further, the mass ratio of at least one selected from the group consisting of aspartic acid and its salt in the composition of the present invention and the content of gamma-oryzanol is not particularly limited, but aspartic acid is used from the viewpoint of suppressing the decrease in the content of gamma-oryzanol. And 0.001 to 150 parts by mass of gamma oryzanol, preferably 0.001 to 20 parts by mass, more preferably 0 to 1 part by mass in total of at least one selected from the group consisting of the salts thereof. It is particularly preferable to contain 0.005 to 5 parts by mass.

In one preferred embodiment of the present invention, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, garlic processing The composition containing 1 or more types chosen from the group which consists of a thing and a vitamin B group is mentioned. The combination of one or more selected from the group consisting of aspartic acid and salts thereof and one or more selected from the group consisting of processed garlic and vitamin B group is as specifically disclosed in Test Example 5 below. , Has an excellent eye strain recovery action.
In this embodiment, the “one or more selected from the group consisting of processed garlic and vitamin B group” is preferably an embodiment including both the processed garlic product and vitamin B group. In addition, it is more preferable to include one or more vitamin B groups selected from the group consisting of vitamin B1, vitamin B2, vitamin B6, and vitamin B12. In addition to the processed garlic, vitamin B1, vitamin B2, More preferably, it is an embodiment containing two or more types of vitamin B selected from vitamin B6 and vitamin B12, and in addition to the processed garlic, three or more types selected from vitamin B1, vitamin B2, vitamin B6 and vitamin B12 It is even more preferable that the vitamin B group is included. Processed garlic, Vita Down B1, vitamin B2, the combination of vitamin B6 and vitamin B12 are particularly preferable.
In addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, the composition of the present invention is further processed garlic and vitamin B In the case of a composition containing a group, the mass ratio of the processed garlic product and the vitamin B group is not particularly limited, but from the viewpoint of an eye strain recovery action, the vitamin B content is 1 part by mass of the processed garlic product. The group is preferably 0.0000002 to 1500 parts by mass, more preferably 0.000005 to 100 parts by mass, and particularly preferably 0.00005 to 25 parts by mass.

  In addition to at least one selected from the group consisting of aspartic acid and its salt, and at least one selected from the group consisting of adenosine triphosphate and its salt, it further contains both garlic processed products and vitamin B group. The composition of the present invention of the aspect is excellent in stability of the processed garlic product and vitamin B group in addition to one or more kinds of stability selected from the group consisting of adenosine triphosphate and a salt thereof, and is derived from the processed garlic product. Since the odor is suppressed, it is easy to use, the vitamin B group stability is good, the quality stability over time is particularly good, and it has an excellent eye fatigue recovery action. It can be suitably used for the treatment and alleviation of fatigue (particularly accommodative eye strain).

In addition to the above components, other drugs and Chinese medicine formulations can be blended in the composition of the present invention depending on the purpose of use.
Specific examples of the drug include retinols (retinol acetate, retinol palmitate, vitamin A oil, etc.), liver oils (liver oil, strong liver oil, etc.), vitamin Ds (ergocalciferol, cholecalciferol, etc.), Vitamin Cs (ascorbic acid, calcium ascorbate, sodium ascorbate, etc.), ursodeoxycholic acid, amino acids (L-cysteine hydrochloride, L-cysteine, L-lysine lysine, L-arginine hydrochloride, L-methionine, DL- Methionine, L-isoleucine, L-leucine, L-phenylalanine, L-threonine, L-tryptophan, L-valine, aminoethylsulfonic acid, etc., orotic acid, calcium salts (calcium glycerophosphate, calcium gluconate, precipitated calcium carbonate, Lactic acid cal ), Anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, calcium citrate, etc.), magnesium salts (magnesium carbonate, etc.), glucuronic acids (glucuronolactone, glucuronic acid amide, etc.), chondroitin sulfate sodium, diisopropylamine dichloroacetate, liver Hydrolysates, carrots (carrots), yokuinin (yokujin), yakuyoku, rokujo (deer moth), hampi (anti-nose), goo (oxen), royal jelly, seisei (kosei), kokushi (coconut), borei (oyster), Touki (homecoming), Bowie (prevented), Taiso (large coral), Peonies (glaze), Syougyo (ginger), Ezokogi (蝦 夷 五 加), Ogi (yellow ginger), Kojin (red bean paste), Kaikujin ( (Kaijin kidney), Kashuu (what neck), Guarana, Psycho (Shibahu), Senkyu ( Kyu), crates, bukuryo (茯苓), methylmethionine sulfonium chloride, caffeine (caffeine, anhydrous caffeine, sodium benzoate caffeine, etc.), inositol, carnitine chloride, rutin, decongestant (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, berberine sulfate, sodium azulene sulfonate, Dipotassium glycyrrhizinate, zinc sulfate, zinc lactate, lysozyme chloride, etc.), antihistamines (diphenhydramine hydrochloride, chlorpheniramine maleate) ), Sulfa drugs (sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, sulfisomidine sodium), inorganic salts (potassium chloride, calcium chloride, sodium chloride, sodium bicarbonate, sodium carbonate, 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.), alkyl Examples thereof include polyaminoethylglycine and boric acid, 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 present invention, the “composition” may be in a solid, semi-solid, or liquid form, and is usually used in pharmaceuticals, quasi-drugs, cosmetics, foods, etc. depending on the purpose of use. It can be a shape. 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 present invention, it is preferably a solid composition, more preferably a solid preparation such as tablets, capsules (excluding liquid-filled capsules), pills, granules, powders, fine granules, Particularly preferred are tablets. As described in Test Example 4 below, one or more selected from the group consisting of aspartic acid and its salts have excellent binding ability, and can be used as a formulation additive in a solid composition as a binder. It became clear. Therefore, when the composition of the present invention is solid, it can be formulated without using other binders, and the types and amounts of components such as formulation additives blended in the composition can be reduced. As a result, it has an excellent effect that the composition can be produced at a low cost. In particular, when the solid composition is a tablet, the hardness of the tablet can be increased. Therefore, according to the present invention, it is possible to provide a tablet in which breakage during distribution is suppressed.

  The composition of the present invention is a known method in the pharmaceutical field, quasi-drug field, cosmetics field, food field, etc., depending on the specific shape, for example, the method described in the 15th revised Japanese Pharmacopeia Can be manufactured according to. 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 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 of the present invention can be used as pharmaceuticals, quasi drugs, cosmetics, foods, etc., depending on the action of the components contained in the composition, for example, nourishing tonic health agents, vitamin main drug formulations, vitamin-containing health agents, etc. Available as 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. In particular, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, further from the group consisting of processed garlic and vitamin B group The composition of the present invention containing at least one selected from the group consisting of at least one selected from the group consisting of aspartic acid and salts thereof, and at least one selected from the group consisting of processed garlic and vitamin B group Can be suitably used as a composition for improving eye strain based on the excellent eye strain recovery effect achieved by combining the above. Here, “a composition for improving eye strain” means a composition used for the treatment and alleviation of eye strain (especially regulatory eye strain) and is suitably used as a pharmaceutical product or a quasi-drug. It can be done.

  Next, one or more stabilization methods selected from the group consisting of adenosine triphosphate and salts thereof of the present invention will be described.

The stabilization method is characterized in that at least one selected from the group consisting of adenosine triphosphate and a salt thereof and at least one selected from the group consisting of aspartic acid and a salt thereof coexist. .
In the stabilization method of the present invention, “to coexist” one or more selected from the group consisting of adenosine triphosphate and its salt and one or more selected from the group consisting of aspartic acid and its salt are both It means creating a state where the components are present in the same system (for example, in the same composition, in the same closed system, etc.) directly or indirectly. Therefore, in addition to both components actively present in the same system, the case where both components are present in the same system due to changes in the components, etc. is also included in the stabilization method of the present invention. The

  In the stabilization method of the present invention, for example, a mode in which one or more selected from the group consisting of adenosine triphosphate and a salt thereof and one or more selected from the group consisting of aspartic acid and a salt thereof coexist is, for example, adenosine A mode in which one or more selected from the group consisting of triphosphate and its salt and one or more selected from the group consisting of aspartic acid and its salt are mixed; selected from the group consisting of adenosine triphosphate and its salt The aspect etc. which contain 1 or more types and 1 or more types chosen from the group which consists of aspartic acid and its salt in the same composition (especially solid composition), etc. are mentioned.

  Specific examples of the stabilization method of the present invention include the following methods (a) to (d).

(A) one or more members selected from the group consisting of aspartic acid and salts thereof and one or more members selected from the group consisting of adenosine triphosphates and salts thereof, and adenosine triphosphates, One or more stabilization methods selected from the group consisting of the salts.

(B) one or more selected from the group consisting of aspartic acid and salts thereof, and one or more selected from the group consisting of adenosine triphosphates and salts thereof, and adenosine triphosphate, One or more stabilization methods selected from the group consisting of the salts.

(C) One or more selected from the group consisting of aspartic acid and its salt and one or more selected from the group consisting of adenosine triphosphate and its salt are contained in the same composition. One or more stabilization methods selected from the group consisting of adenosine triphosphate and salts thereof.

(D) One or more selected from the group consisting of aspartic acid and its salt and one or more selected from the group consisting of adenosine triphosphate and its salt are contained in the same composition. 1 or more content fall control methods chosen from the group which consists of adenosine triphosphate and its salt in a composition.

  In the stabilization 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 in the case of the above 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] Evaluation of stability of one or more selected from the group consisting of adenosine triphosphate and its salt By the following test, one or more high temperature conditions selected from the group consisting of adenosine triphosphate and its salt The stability under was confirmed.
Samples 1-A and 1-B shown below were prepared and stored at 60 ° C. for 1 week, respectively, and the content of disodium adenosine triphosphate in the samples after storage for 2 days and 1 week was determined using the Japanese Pharmacopoeia. It quantified according to the determination method of adenosine triphosphate disodium described in the foreign pharmaceutical 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 was 100% at the start of storage, and this residual rate was used as an index of content stability. .
Separately, at the start of storage, the state (appearance) of the drug in each sample after storage for 2 days and after storage for 1 week was visually evaluated.
The results of content stability evaluation are shown in Table 1, and the appearance evaluation results are shown in Table 2.

[Sample 1-A]
250 mg of adenosine triphosphate disodium (adenosine triphosphate disodium: Kyowa Hakko Bio Co., Ltd.) was placed in a glass bottle (2K standard bottle) to give sample 1-A.
[Sample 1-B]
After thoroughly mixing 250 mg of adenosine triphosphate disodium (adenosine triphosphate disodium: Kyowa Hakko Bio Co., Ltd.) and 250 mg of magnesium L-aspartate (magnesium L-aspartate: Alps Pharmaceutical Industries, Ltd.) Sample 1-B was placed in a glass bottle (2K standard bottle).

From the results of Table 1, sample 1-A in which disodium adenosine triphosphate was used alone in a glass bottle without using magnesium L-aspartate showed almost no adenosine triphosphate remaining when stored for 1 week. I understood.
On the other hand, it was found that in Sample 1-B in which L-magnesium aspartate was coexisted with adenosine triphosphate disodium, the decrease in content after storage for 1 week was greatly suppressed.
From the above, it has been clarified that magnesium L-aspartate has a stabilizing action of disodium adenosine triphosphate.
Further, from the results of Table 2, sample 1-B in which L-magnesium aspartate coexists with adenosine triphosphate disodium is more stable in appearance than sample 1-A in which L-aspartate is not used. It became clear that it was excellent in terms of sex.

From the above test results, at least one selected from the group consisting of aspartic acid and its salt has at least one stabilizing action selected from the group consisting of adenosine triphosphate and its salt under high temperature conditions, It became clear that content stability with time was improved.
Therefore, according to the present invention, it is possible to provide a composition having good quality stability over time and at least one selected from the group consisting of adenosine triphosphate and a salt thereof and excellent in quality.

[Reference Example 1]
Salt of aspartic acid (potassium L-aspartate / magnesium: Alps Yakuhin Kogyo Co., Ltd.) 2400 g, processed garlic (Oxoamidin powder: Riken Chemical Co., Ltd.) 480 g, Vitamin B1 (benfotiamine: Yonezawa Hamari Pharmaceutical Co., Ltd.) Ltd.) 1106.4 g, vitamin B2 (riboflavin Riboflavin High Flow 100: BASF Japan Ltd.) 96 g, vitamin B6 (pyridoxine hydrochloride: DSM Nutrition Japan Ltd.) 400 g, vitamin B12 (cyanocobalamin gelatin granules RIKEN dry B12) -B1-CN-GP: Riken Vitamin Co., Ltd. (480 g), Gamma-Oryzanol (γ-Oryzanol: Oriza Oil Chemical Co., Ltd.) 80 g, Hydroxypropylcellulose (HPC-L: Nippon Soda Co., Ltd.) 194.4 , Calcium silicate (FLORITE RE: Tokuyama Co., Ltd.) 64.8g, crospovidone (Polyplastidon XL: IS Japan Co., Ltd.) 518.4g, high-speed stirring granulator (vertical granulator FM-VG) -25: (Paulec Co., Ltd.) and ethanol was added to prepare a granulated product. This was dried with a fluidized bed dryer (flow coater FLO-5B: Freund Sangyo Co., Ltd.), and then the dried product was sized with a granulator (New Speed Mill ND-10S: Okada Seiko Co., Ltd.). .

5820 g of the obtained sized product, 414.3 g of vitamin E (dl-α-tocopherol calcium succinate: Tama Biochemical Co., Ltd.), 129.6 g of calcium silicate (FLORITE RE: Tokuyama Co., Ltd.), crystalline cellulose (Theoras PH-102: Asahi Kasei Chemicals Co., Ltd.) 51.3 g and magnesium stearate (magnesium stearate: Taihei Chemical Industry Co., Ltd.) 64.8 g are mixed in a mixer (Bole container mixer PM-50: Kotobuki Giken Kogyo Co., Ltd.) )) And mixed to obtain granules for tableting.
This was tableted with a rotary tableting machine (HP-AP18-SS: Hata Plant) to produce 270 mg uncoated tablets per tablet.
To the obtained uncoated tablet 6480 g, a suspended protective coating solution comprising 384 g of hypromellose (TC-5R: Shin-Etsu Chemical Co., Ltd.), 96 g of talc (talc MS: Nippon Talc Co., Ltd.) and 4320 g of purified water, Drying was carried out while spraying the protective coating solution with a coating machine (Dria Coater DRC-650DS: POWREC Co., Ltd.) to obtain 280 mg of protected tablets per tablet.
To 6720 g of the obtained protective latch, 1472 g of purified white sugar (Granu sugar CH: Shimizu Minato Sugar Co., Ltd.), 2496 g of talc (Talc MS: Nihon Talc Co., Ltd.), precipitated calcium carbonate (Calcy F: Sankyo Seiko Co., Ltd.) )) 2496 g, gum arabic (Gum arabic powder: Nippon Powder Chemical Co., Ltd.) 608 g, gelatin (gelatin E1: Nippi Co., Ltd.) 128 g and purified underwater solution 2400 g using a suspension undercoat liquid (Doria Coat DRC-650DS (Paulec Co., Ltd.) was dried while spraying the undercoat liquid to obtain 430 mg of undercoat tablets per tablet.

10320 g of the obtained undercoat tablets were added 2208 g of purified sucrose (Granu sugar CH: Shimizu Minato Seika Co., Ltd.), 176 g of titanium oxide (titanium oxide NA-61: Toho Titanium Co., Ltd.), gelatin (gelatin E1: Co., Ltd.) Nippi) Using a suspended color solution consisting of 16 g and 1280 g of purified water, drying was performed while spraying the color solution with a coating machine (Dria Coater DRC-650DS: POWREC Co., Ltd.), and 480 mg per tablet. A colored tablet was obtained.
A coating machine (Dria Coater DRC-650DS: Co., Ltd.) was used with 11520 g of the resulting colored tablet using a dissolved overcoat solution consisting of 240 g of purified sucrose (Granu sugar CH: Shimizu Minato Seika Co., Ltd.) and 128 g of purified water The powder was dried while spraying the overcoat liquid, and 485 mg of overcoat tablets per tablet was obtained.
Carnauba wax (Polishing wax 103: Freund Sangyo Co., Ltd.) 1.2 g is added to 11640 g of the obtained overhanging tablet and polished with a coating machine (Doria Coater DRC-650DS: Powrec Co., Ltd.). 485 mg dragees were obtained per tablet.

[Comparative Example 1]
A sugar-coated tablet of 485 mg per tablet was obtained in the same manner as in Reference Example 1 except that crystalline cellulose (Theolas PH-101: Asahi Kasei Chemicals Corporation) was used instead of the salt of aspartic acid.

[Test Example 2] Evaluation of suppression of odor derived from processed garlic product 180 tablets of each tablet obtained in Reference Example 1 and Comparative Example 1 at 25 ° C. and 60% RH for 8 hours, 1 day, 3 days And about the generation of odor when stored for 1 week,
0: No unpleasant odor derived from processed garlic 1: No unpleasant odor derived from processed garlic 2: 2 Unpleasant odor derived from processed garlic 3: Strongly felt unpleasant odor derived from processed garlic Evaluation was made in 4 stages. The evaluation was performed by 10 people, and the average value was calculated. The results are shown in Table 3.

  From the results of Table 3, in the tablet of Comparative Example 1 not containing potassium L-aspartate / magnesium, an unpleasant odor derived from processed garlic was felt after storage for 1 day. On the other hand, in the tablet of Reference Example 1 containing potassium L-aspartate / magnesium, an unpleasant odor derived from the processed garlic was hardly felt even after storage for 1 week.

From the above test results, it has been clarified that one or more selected from the group consisting of aspartic acid and its salts have an action of suppressing odors derived from processed garlic.
Although the cause and mechanism of odors derived from processed garlic are not clear, the odor derived from garlic is generally thought to be generated by oxidation with oxygen in the air, so that the processed garlic comes into contact with air. This is particularly a problem for easy solid compositions. According to the present invention, even when the composition is in a solid state as in the above test examples, the odor derived from the processed garlic was effectively suppressed.
Therefore, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, the garlic processed product of the present invention is further included. In the composition, only one or more selected from the group consisting of adenosine triphosphate and its salt, based on the odor control action derived from the processed garlic product having at least one selected from the group consisting of aspartic acid and its salt It was speculated that the processed garlic was also excellent in stability.

[Test Example 3] Evaluation of content stability of vitamin B group, vitamin E and gamma-oryzanol 180 tablets each obtained in Reference Example 1 and Comparative Example 1 were packaged using a glass bottle and a metal cap, It was stored for 2 months and 4 months under the condition of 75% RH. After each storage period, the tablets were taken out from the bottles, and the contents of benfotiamine, riboflavin, pyridoxine hydrochloride, cyanocobalamin, dl-α-tocopherol calcium succinate and gamma-oryzanol were measured according to Benfoth described in the Japanese Pharmacopoeia Standard 1997. Thiamine Determination Method, Fifteenth Amendment Japanese Pharmacopoeia Quantitative Method of Riboflavin as described in Articles of Pharmaceuticals, Fifteenth Amendment Japanese Pharmacopoeia Quantitation method of pyridoxine hydrochloride described in each item of Pharmaceuticals, Fifteenth Amendment Japanese Pharmacopoeia Drugs Quantification according to the quantitative method of cyanocobalamin described in each article, the quantitative method of calcium tocopherol succinate described in 2006 quasi-drug raw material standard, and the quantitative method of gamma-oryzanol described in quasi-drug raw material standard 2006 The content of each drug was calculated. The content of each obtained drug after each storage period was evaluated as a relative value (residual rate) when the content at the start of the test was taken as 100%, and used as an index of content stability. The results are shown in Tables 4-9.

  From the results of Tables 4 to 9, in the tablet of Comparative Example 1 not containing potassium L-aspartate / magnesium, about 3% of benfotiamine, riboflavin, and gamma-oryzanol after storage for 4 months, pyridoxine hydrochloride, succinic acid A decrease in content of about 4% was observed for tocopherol calcium and about 11% for cyanocobalamin. On the other hand, the tablet of Reference Example 1 containing potassium L-aspartate / magnesium was excellent in content stability with almost no decrease in content observed after storage for 4 months. Accordingly, it has been clarified that potassium L-aspartate / magnesium has an action of suppressing a decrease in the content of benfotiamine, riboflavin, pyridoxine hydrochloride, cyanocobalamin, dl-α-tocopherol calcium succinate and gamma-oryzanol. In particular, the inhibitory effect of the content reduction with respect to cyanocobalamin was remarkable.

From the above test results, at least one selected from the group consisting of aspartic acid and its salts is an inhibitory effect on the decrease in the content of vitamin B group such as vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin E and gamma-oryzanol. It was revealed that the content stability over time was increased.
Therefore, in addition to one or more selected from the group consisting of aspartic acid and its salt and one or more selected from the group consisting of adenosine triphosphate and its salt, it further comprises vitamin B group, vitamin E and gamma oryzanol. In the composition of the present invention containing at least one selected from the group, adenosine triphosphate is based on the inhibitory action on the decrease in the content of one or more components selected from the group consisting of aspartic acid and salts thereof. It was speculated that the stability of vitamin B group, vitamin E, and gamma oryzanol was excellent as well as one or more selected from the group consisting of acids and salts thereof.

[Reference Example 2]
Salt of aspartic acid (potassium L-aspartate / magnesium: Alps Yakuhin Kogyo Co., Ltd.) 2400 g, processed garlic (Oxoamidin powder: Riken Chemical Co., Ltd.) 480 g, Vitamin B1 (benfotiamine: Yonezawa Hamari Pharmaceutical Co., Ltd.) 1106.4 g, vitamin B2 (riboflavin Riboflavin High Flow 100: BASF Japan Ltd.) 96 g, vitamin B6 (pyridoxine hydrochloride: DSM Nutrition Japan Ltd.) 400 g, vitamin B12 (cyanocobalamin gelatin granular physics laboratory dry) B12-B1-CN-GP: Riken Vitamin Co., Ltd. (480 g), Gamma-Oryzanol (γ-Oryzanol: Oriza Oil Chemical Co., Ltd.) 80 g, Crystalline Cellulose (Theoras PH-101: Asahi Kasei Chemicals Co., Ltd.) 19 .4 g, calcium silicate (FLORITE RE: Tokuyama Co., Ltd.) 64.8 g, crospovidone (Polyplastidon XL: IS Japan Co., Ltd.) 518.4 g, high-speed agitation granulator (vertical granulator FM -VG-25: (Paulec Co., Ltd.) and ethanol was added to prepare a granulated product. This was dried with a fluidized bed dryer (flow coater FLO-5B: Freund Sangyo Co., Ltd.), and then the dried product was sized with a granulator (New Speed Mill ND-10S: Okada Seiko Co., Ltd.). .

5820 g of the obtained sized product, 414.3 g of vitamin E (dl-α-tocopherol calcium succinate: Tama Biochemical Co., Ltd.), 129.6 g of calcium silicate (FLORITE RE: Tokuyama Co., Ltd.), crystalline cellulose (Theoras PH-102: Asahi Kasei Chemicals Co., Ltd.) 51.3 g and magnesium stearate (magnesium stearate: Taihei Chemical Industry Co., Ltd.) 64.8 g are mixed in a mixer (Bole container mixer PM-50: Kotobuki Giken Kogyo Co., Ltd.) )) And mixed to obtain granules for tableting.
This was tableted on a rotary tableting machine (HP-AP18-SS: Hatabekosho) under the conditions of tableting pressure: 600, 900, 1200, 1500 or 1800 kg / cm ² , and 270 mg per tablet. Tablets were made.

[Comparative Example 2]
Tablets of 270 mg per tablet were produced in the same manner as in Reference Example 2 except that crystalline cellulose (Theolas PH-101: Asahi Kasei Chemicals Corporation) was used instead of the aspartic acid salt.

[Test Example 4] Evaluation of hardness of tablets containing at least one selected from the group consisting of aspartic acid and salts thereof The hardness of the tablets obtained in Reference Example 2 and Comparative Example 2 was measured. Specifically, the tablets of Reference Example 2 and Comparative Example 2 were each 20 tablets for each tableting pressure condition, and the tablet hardness was measured for each tablet with a tablet hardness meter (PTB-311E: PHARMATET). The value was calculated. The results are shown in Table 10.

  From the results shown in Table 10, the tablet of Reference Example 2 containing an aspartic acid salt has a hardness of about 2 at any tableting pressure compared to the tablet of Comparative Example 2 containing no aspartic acid salt. Doubled.

From the above test results, it has been found that at least one selected from the group consisting of aspartic acid and its salt has an effect of enhancing the hardness of the tablet. Moreover, from this, it has been clarified that one or more selected from the group consisting of aspartic acid and salts thereof have excellent binding ability and can be used as a binder in a solid composition.
Therefore, when the composition of the present invention is solid, it can be formulated without using other binders, and can be produced while reducing the types and amounts of ingredients such as formulation additives to be blended in the composition. it can.

[Test Example 5] Evaluation of eye fatigue recovery action using ciliary muscle fatigue model Ciliary muscle fatigue model according to the following test method with reference to the test method described in JP-A-2003-10158 The effect of enhancing the ciliary muscle contraction force was evaluated and used as an index for the recovery from eye strain.

A male white rabbit (purchased from Nippon Medical Sciences Animal Materials Laboratory Co., Ltd.) was killed by pentobarbital overanesthesia, and the eyeball was immediately removed to prepare a ciliary muscle sample with a width of about 5 mm in the circumferential direction. did. One end of the sample was connected to a Magnus experimental apparatus (isometric transducer (TRI 202P: manufactured by Letica)), and a buffer solution (118.0 mM NaCl, 4 and 4%) at 37 ° C. was aerated with a mixed gas of 95% oxygen and 5% carbon dioxide. .7 mM KCl, 2.5 mM CaCl ₂ , 1.2 mM KH ₂ PO ₄ , 25.0 mM NaHCO ₃ , 11.1 mM glucose: pH 7.8) suspended in a Magnus tank filled with 20 mL under a load of 0.1 g did. The tension change was recorded by a recorder via a transducer.
After standing for about 30 minutes after the above operation, 10 μL of a contracting agent (1 mM Carbachol (manufactured by SIGMA)) is added to the buffer solution to induce the contraction reaction of the ciliary muscle, and the contraction force reaches the maximum peak. Washed with buffer until lowered to baseline. The contraction force was reduced by about 70% from the start of the test by repeating this addition / washing operation of about 8 times to repeatedly contract and relax the ciliary muscle, and a ciliary muscle fatigue model was created. In the above-mentioned contraction agent addition / washing operation, the maximum peak value of contraction force due to the last one contraction agent addition was defined as the contraction force (Pre value) immediately before drug addition.
In the ciliary muscle fatigue model created by the above method, the test drug was added to the buffer solution in the Magnus tank, a contraction agent was added after 10 minutes, and the maximum peak value (Post value) of the contractile force was measured. The obtained Post value was evaluated as a contractile force enhancement rate (%) as a relative value with a Pre value of 100. Further, a value obtained by dividing the Post value by the Pre value was evaluated as a relative index.

  The test drug is divided into three groups: a component (A) administration group, a component (B) administration group, and a combination administration group of components (A) and (B) ((A) + (B) administration group). Each drug was dissolved in water for injection and added so that the final concentration in the buffer in the tank would be the following concentration.

Component (A): Aspartic acid (potassium aspartate / magnesium: Nissei Chemical Industry Co., Ltd.) 550 μg / mL
Ingredient (B): Processed garlic (oxoamidin powder: manufactured by Riken Chemical Industry Co., Ltd.) 110 μg / mL, vitamin B1 (benfotiamine: manufactured by Kongo Chemical Co., Ltd.) 250 μg / mL, vitamin B2 (riboflavin: DSM Nutrition Japan) 22 μg / mL, vitamin B6 (pyridoxine hydrochloride: Takeda Pharmaceutical Co., Ltd.) 91 μg / mL, vitamin B12 (cyanocobalamin: Wako Pure Chemical Industries, Ltd.) 0.11 μg / mL

In addition, the test of 3 to 4 cases was performed for each test drug administration group for each group.
The results are shown in Table 11. The contractile force enhancement rate was expressed as an average value ± standard error, and the relative index was expressed as an average value.

  From the results of Table 11, in the single administration group of the components (A) and (B), the enhancement of the contractile force of the ciliary muscle about 1.2 to 1.3 times that before drug administration was observed. However, it was not a significant effect. However, in the combination administration group of components (A) and (B), about 2 times as much enhancement of the contractile force of the ciliary muscle was observed as compared with that before drug administration. The relative index is 1.24 in the component (A) administration group and 1.33 in the component (B) group, and the product (1.65) is the combination administration group of components (A) and (B). It was concluded that the combination of components (A) and (B) exerted a synergistic effect on the enhancement of ciliary muscle contractile force by the bulge method.

Based on the above test results, an excellent eye strain recovery action can be obtained by combining at least one selected from the group consisting of aspartic acid and salts thereof and at least one selected from the group consisting of processed garlic and vitamin B group. Compared to the case where one or more selected from the group consisting of aspartic acid and its salt and one or more selected from the group consisting of processed garlic and vitamin B group are administered separately. It was clarified that a synergistic effect was obtained for the fatigue recovery action.
Therefore, in addition to one or more selected from the group consisting of aspartic acid and its salt, and one or more selected from the group consisting of adenosine triphosphate and its salt, further from the group consisting of processed garlic and vitamin B group It was speculated that the composition of the present invention containing one or more selected types can be suitably used as a composition for improving eye strain.

[Example 1]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
300 mg of potassium aspartate / magnesium equivalent mixture
Fursultiamine hydrochloride 109.16mg
Pyridoxine hydrochloride 100mg
Cyanocobalamin 1500μg
Dl-α-Tocopherol calcium succinate 103.58mg
Calcium pantothenate 30mg
Gamma oryzanol 10mg
Riboflavin 800μg
Erythritol 122.16mg
Crystalline cellulose 130mg
Hydroxypropylcellulose 40.8mg
Carmellose calcium 61.2mg
Magnesium stearate 10.8mg

[Example 2]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
300 mg of potassium aspartate / magnesium equivalent mixture
Oxoamidin powder 60mg
Benfotiamine 138.3mg
Riboflavin 12mg
Pyridoxine hydrochloride 50mg
Cyanocobalamin 60μg
Gamma oryzanol 10mg
Dl-α-Tocopherol calcium succinate 103.6mg
D-mannitol 106mg
Crystalline cellulose 120.1mg
Hydroxypropylcellulose 37.5mg
Carmellose calcium 45mg
Magnesium stearate 7.5mg

[Example 3]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
Potassium aspartate / magnesium equivalent mixture 140mg
Oxoamidin powder 50mg
30 mg of thiamine nitrate
Riboflavin 4mg
Pyridoxine hydrochloride 24mg
Cyanocobalamin 60μg
Hardened oil 24mg
Crystalline cellulose 100mg
Hydroxypropylcellulose 20mg
Carmellose calcium 24mg
Magnesium stearate 4mg

[Example 4]
Tablets containing the following components in 9 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
30 mg of thiamine nitrate
Sodium chondroitin sulfate 800mg
300 mg of potassium aspartate / magnesium equivalent mixture
Dl-α-Tocopherol calcium succinate 30mg
Glucosamine hydrochloride 1000mg
Hydroxypropylcellulose 97mg
Magnesium stearate 23mg

[Example 5]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
Bisbenchamine 114.32mg
Riboflavin 12mg
Pyridoxine hydrochloride 50mg
Cyanocobalamin 0.06mg
Dl-α-Tocopherol calcium succinate 103.6mg
Potassium aspartate / magnesium equivalent mixture 200mg
D-mannitol 116mg
Crystalline cellulose 123.2mg
Hydroxypropylcellulose 37.5mg
Carmellose calcium 45mg
Magnesium stearate 7.5mg

[Example 6]
Tablets containing the following components in 9 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
Benfotiamine 30mg
Sodium chondroitin sulfate 800mg
Potassium aspartate / magnesium equivalent mixture 200mg
Processing Oiso 100mg
Glucosamine hydrochloride 1000mg
Hydroxypropylcellulose 115mg
Magnesium stearate 25mg

[Example 7]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
Potassium aspartate / magnesium equivalent mixture 200mg
Fursultiamine hydrochloride 109.16mg
Pyridoxine hydrochloride 20mg
Cyanocobalamin 60μg
Riboflavin 12mg
Calcium pantothenate 15mg
Hardened oil 36mg
Lactose hydrate 147.8mg
Hydroxypropylcellulose 24mg
Carmellose calcium 30mg
Magnesium stearate 6mg

[Example 8]
Tablets containing the following components in 2 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 40mg
Potassium aspartate / magnesium equivalent mixture 200mg
Retinol palmitate 2000 Vitamin A unit dicetiamine hydrochloride 10mg
Riboflavin 6mg
Pyridoxine hydrochloride 8mg
Nicotinamide 50mg
Ascorbic acid 150mg
Cholecalciferol 200 International Units d-α-Tocopherol acetate 15mg
Anhydrous calcium hydrogen phosphate 68mg
Precipitated calcium carbonate 300mg
Magnesium carbonate 79mg
Hardened oil 40mg
Crystalline cellulose 144mg
Hydroxypropylcellulose 30mg
Carmellose 30mg
Calcium stearate 6mg

[Example 9]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
Potassium aspartate / magnesium equivalent mixture 200mg
Fursultiamine hydrochloride 100mg
Pyridoxine hydrochloride 20mg
Cyanocobalamin 60μg
Sodium chondroitin sulfate 800mg
Glucosamine hydrochloride 214mg
Hardened oil 36mg
Hydroxypropylcellulose 24mg
Carmellose calcium 30mg
Magnesium stearate 12mg

[Example 10]
Tablets containing the following components in 2 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 40mg
Thiamine nitrate 10mg
Riboflavin 8mg
Pyridoxine hydrochloride 40mg
Nicotinamide 50mg
Dl-α-Tocopherol calcium succinate 15mg
Potassium aspartate / magnesium equivalent mixture 200mg
L-cysteine 90mg
DL-methionine 15mg
Psycho dried extract 30mg (Drug substance equivalent amount 240mg)
Senkyu dry extract 10mg (100mg of crude drug equivalent)
Krategus dry extract 12mg (Drug substance equivalent amount 120mg)
Bukuryu dried extract 20mg (Drug substance equivalent amount 400mg)
Hydroxypropylcellulose 24mg
Crystalline cellulose 119mg
Carmellose 30mg
Magnesium stearate 7mg

[Example 11]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
Mecobalamin 1500μg
Folic acid 5mg
D-α-Tocopherol acetate 100mg
Fursultiamine hydrochloride 109.16mg
Pyridoxine hydrochloride 100mg
Potassium aspartate / magnesium equivalent mixture 100mg
Hydroxypropylcellulose 24mg
Corn starch 130.3mg
Carmellose 24mg
Magnesium stearate 6mg

[Example 12]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 60mg
L-magnesium aspartate 10mg
Oxoamidin powder 60mg
Benfotiamine 138.3mg
Calcium pantothenate 30mg
Cyanocobalamin 60μg
Dl-α-Tocopherol calcium succinate 51.79 mg
Gamma oryzanol 10mg
Hydroxypropylcellulose 16.7mg
Crystalline cellulose 111.55mg
Crospovidone 55.5mg
Magnesium stearate 11.1mg

[Example 13]
Tablets containing the following components in 3 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 20mg
L-magnesium aspartate 100mg
Bisbentiamine 100mg
Pyridoxine hydrochloride 100mg
Cyanocobalamin 1500μg
Dl-α-Tocopherol calcium succinate 103.58mg
Hepronicart 100mg
Hardened oil 36mg
D-mannitol 93mg
Crystalline cellulose 120mg
Hydroxypropylcellulose 24mg
Croscarmellose sodium 36mg
Magnesium stearate 6mg

[Example 14]
Tablets containing the following components in 2 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 40mg
Potassium aspartate / magnesium equivalent mixture 200mg
Benfotiamine 138.3mg
Inositol hexanicotinate 200mg
Riboflavin 6mg
Pyridoxine hydrochloride 10mg
Cyanocobalamin 60μg
Oxoamidin powder 20mg
Hardened oil 24mg
Crystalline cellulose 113.4mg
Hydroxypropylcellulose 20mg
Croscarmellose sodium 24mg
Magnesium stearate 4mg

[Example 15]
Tablets containing the following components in 4 tablets (daily dose) were produced by a conventional method.
Adenosine triphosphate disodium 40mg
Potassium aspartate / magnesium equivalent mixture 100mg
Riboflavin sodium phosphate 15mg
Pyridoxine hydrochloride 15mg
Thiamine nitrate 10mg
Royal jelly tincture 100mg
Aminoethylsulfonic acid 1000mg
Nicotinamide 20mg
Anhydrous caffeine 50mg
D-mannitol 94mg
Corn starch 120mg
Hydroxypropylcellulose 24mg
Carmellose 36mg
Magnesium stearate 16mg

  According to the present invention, a composition having a high quality and a good commercial value, in which a decrease in the content of one or more selected from the group consisting of adenosine triphosphate and a salt thereof generated over time is suppressed and stability is improved. And can be used in the pharmaceutical industry, cosmetics industry, food industry and the like.

Claims (7)

A composition containing one or more selected from the group consisting of aspartic acid and salts thereof, and one or more selected from the group consisting of adenosine triphosphate and salts thereof. However, the following (1) to ( 7 ) are excluded.
(1) A drug preparation containing inosine, adenosine triphosphate, vitamin C, potassium aspartate, magnesium aspartate, and other vitamin substances.
(2) A drug formulation containing inosine, adenosine triphosphate, vitamin C, aspartic acid and ornithine.
(3) Maintaining healthy longevity of the human body characterized by selectively using a composition of charanthin, polydatin, superoxide dismutase, adenosine triphosphate, L-aspartic acid, vitamin P, excipients and auxiliary materials Alkaline high energy agent.
(4) vitamin B1, vitamin B2, vitamin B6, vitamin B12, pantothenic acid, nicotinic acid, pyridoxine, folic acid, acetylcholine, inositol, biotin, niacin, alanine, arginine, aspartic acid, isoleucine, leucine, lysine, methionine, phenylalanine, Threonine, tryptophan, glutamic acid, valine, proline, tyrosine, taurine, glycine, γ-aminobutyric acid, histidine, β-alanine, serine, cysteine, calcium, magnesium, sodium, potassium, copper, iron, zinc, manganese, albumin, β A granular preparation containing globulin, α-globulin, γ-globulin, parothin, ATP, hydroxydecenoic acid and R-substance.
(5) Methionine, tryptophan, α-aminoadipic acid, asparagine, cystine, histidine, aspartic acid, alanine, proline, lysine, taurine, isoleucine, ornithine, tyrosine, β-alanine, phosphoserine, α-aminobutyric acid, leucine, arginine , Serine, hydroxylysine, glutamine, glutamic acid, cysteine, phosphoethanolamine, threonine, glycine, phenylalanine, valine, d-pantothenic acid, ascorbic acid, p-aminobenzoic acid, ergocalciferol (D ₂ ), L-carnitine, DL-methionine-S-methyl-sulfonium chloride (U), 2-deoxyadenylic acid (d-AMP), 5'-thymidylic acid (TMP), 2'-deoxycytidine-5-monophosphate (d-CMP) Carnosine, Torurin, _{sarcosine, CaCl 2, Fe (NO 3} ) 9H 2 O, KCl, MgSO 4 7H 2 O, NaCl, NaHCO 3, NaH 2 PO 4 H 2 O, tricine, hemin, HEPES, glucose, D- ribose, 2 -Deoxy-ribose, cholecalciferol (D ₃ ), biotin, pyridoxamine, pyridoxal, cyanocobalamin (B ₁₂ ), choline, thiamine (B ₁ ), inositol, α-tocopherol, 3-phytylmenadione (K ₁ ), menadione (K _3), retinol (A), riboflavin (B _2), 6, 8 thioctic acid, pyridoxine (B _6), folic acid, niacinamide, tetrahydrofolate, adenosine-5-triphosphate (ATP), 2' Deoxyuridine-5-monophosphate (d-UMP), 5′-deoxyguanylic acid (d-GMP) And containing hydroxyproline, medium.
(6) Calcium chloride, sodium bicarbonate, potassium chloride, sodium chloride, monosodium phosphate, glucose, HEPES, ferric nitrate, magnesium sulfate, tricine, D-ribose, 2-deoxyribose, adenosine-5-triphosphorus Acid (ATP), 2-deoxyadenylic acid (d-AMP), 5'-thymidylic acid (TMP), 2'-deoxycytidine-5-monophosphate, 2'-deoxyuridine-5-monophosphate, 2 '-Deoxyguanylic acid (d-GMP), aspartic acid, glutamic acid, L-alanine, arginine, carnosine, cysteine, cystine, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, Threonine, tryptophan, tyrosine, valine, Ascorbic acid, biotin (H), carnitine, cholecalciferol, choline chloride, cyanocobalamin (B _12), ergocalciferol, folic acid, myo-inositol, menadione, nicotinamide, PABA, pantothenate, pyridoxal, pyridoxamine, pyridoxine, retinol (A ), Riboflavin (B ₂ ), thiamine (B ₁ ), 6,8 thioctic acid, alpha-tocopherol, 3-phytylmenadione (K ₁ ), tetrahydrofolic acid, polycine-derived hemin and nanopure water.
(7) L-alanine, L-arginine · HCl, L-asparagine · H ₂ O, L-aspartic acid, L-cystine · 2HCl, L-cysteine · HCl · H ₂ O, L-glutamic acid, glycine, L- Histidine · HCl · H ₂ O, L-isoleucine, L-leucine, L-lysine · HCl, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine · 2Na ⁺ · 2H ₂ O, L-valine, adenine nitrate, ATP, 2-deoxyribose, ethanolamine · HCl, D-glucose, glutathione, HEPES, hypoxanthine · Na ⁺ , linoleic acid, lipoic acid, insulin · Zn ^{+ +,} phenol red, phosphoethanolamine, putrescine · 2HCl, sodium pyruvate, Thymidine, uracil, xanthine, Na ^+, ascorbic acid Mg salt, biotin, choline chloride, D-Ca ⁺⁺ - pantothenate, folic acid, i- inositol, menadione, niacinamide, nicotinic acid, PABA, pyridoxal-HCl, pyridoxine- HCl, riboflavin, thiamine · HCl, vitamin A acetate, vitamin B12, vitamin _{D2, AgNO 3, AlCl 3 ·} 6H 2 O, Ba (C 2 H 3 O 2) 2, CdSO 4 · 8H 2 O, CoCl 2 · 6H ₂ O, Cr (SO ₄ ) ₃ · 15H ₂ O, CuSO ₄ · 5H ₂ O, Fe (NO ₃ ) ₃ · 9H ₂ O, FeSO ₄ · 7H ₂ O, GeO ₂ , H ₂ SeO ₃ , KBr, KI _{, MnCl 2 · 4H 2 O,} NaF, Na 2 SiO 3 · 9H 2 O, NaVO 3, (NH 4) 6 Mo 7 O 24 · 4H 2 O, NiSO 4 · 6 _{2 O, RbCl, SnCl 2,} TiCl 4, ZnSO 4 · 7H 2 O, ZrOCl 2 · 8H 2 O, CaCl 2, KCl, MgCl 2, MgSO 4, NaCl, NaHCO 3, Na 2 HPO 4, NaH 2 PO 4 A medium containing H ₂ O and ferric citrate chelate.   The composition according to claim 1, wherein the composition is solid.   The composition according to claim 1 or 2, which is a tablet. One or more selected from the group consisting of aspartic acid and its salt and one or more selected from the group consisting of adenosine triphosphate and its salt are allowed to coexist, From adenosine triphosphate and its salt One or more stabilization methods selected from the group consisting of: However, the case where it coexists as a composition of the following (1)-(7) is excluded.
(1) A drug preparation containing inosine, adenosine triphosphate, vitamin C, potassium aspartate, magnesium aspartate, and other vitamin substances.
(2) A drug formulation containing inosine, adenosine triphosphate, vitamin C, aspartic acid and ornithine.
(3) Maintaining healthy longevity of the human body characterized by selectively using a composition of charanthin, polydatin, superoxide dismutase, adenosine triphosphate, L-aspartic acid, vitamin P, excipients and auxiliary materials Alkaline high energy agent.
(4) Vitamin B1, vitamin B2, vitamin B6, vitamin B12, pantothenic acid, nicotinic acid, pyridoxine, folic acid, acetylcholine, inositol, biotin, niacin, alanine, arginine, aspartic acid, isoleucine, leucine, lysine, methionine, phenylalanine, Threonine, tryptophan, glutamic acid, valine, proline, tyrosine, taurine, glycine, γ-aminobutyric acid, histidine, β-alanine, serine, cysteine, calcium, magnesium, sodium, potassium, copper, iron, zinc, manganese, albumin, β A granular preparation containing globulin, α-globulin, γ-globulin, parothin, ATP, hydroxydecenoic acid and R-substance.
(5) Methionine, tryptophan, α-aminoadipic acid, asparagine, cystine, histidine, aspartic acid, alanine, proline, lysine, taurine, isoleucine, ornithine, tyrosine, β-alanine, phosphoserine, α-aminobutyric acid, leucine, arginine , Serine, hydroxylysine, glutamine, glutamic acid, cysteine, phosphoethanolamine, threonine, glycine, phenylalanine, valine, d-pantothenic acid, ascorbic acid, p-aminobenzoic acid, ergocalciferol (D ₂ ), L-carnitine, DL-methionine-S-methyl-sulfonium chloride (U), 2-deoxyadenylic acid (d-AMP), 5'-thymidylic acid (TMP), 2'-deoxycytidine-5-monophosphate (d-CMP) Carnosine, Torurin, _{sarcosine, CaCl 2, Fe (NO 3} ) 9H 2 O, KCl, MgSO 4 7H 2 O, NaCl, NaHCO 3, NaH 2 PO 4 H 2 O, tricine, hemin, HEPES, glucose, D- ribose, 2 -Deoxy-ribose, cholecalciferol (D ₃ ), biotin, pyridoxamine, pyridoxal, cyanocobalamin (B ₁₂ ), choline, thiamine (B ₁ ), inositol, α-tocopherol, 3-phytylmenadione (K ₁ ), menadione (K _3), retinol (A), riboflavin (B _2), 6, 8 thioctic acid, pyridoxine (B _6), folic acid, niacinamide, tetrahydrofolate, adenosine-5-triphosphate (ATP), 2' Deoxyuridine-5-monophosphate (d-UMP), 5′-deoxyguanylic acid (d-GMP) And containing hydroxyproline, medium.
(6) Calcium chloride, sodium bicarbonate, potassium chloride, sodium chloride, monosodium phosphate, glucose, HEPES, ferric nitrate, magnesium sulfate, tricine, D-ribose, 2-deoxyribose, adenosine-5-triphosphorus Acid (ATP), 2-deoxyadenylic acid (d-AMP), 5'-thymidylic acid (TMP), 2'-deoxycytidine-5-monophosphate, 2'-deoxyuridine-5-monophosphate, 2 '-Deoxyguanylic acid (d-GMP), aspartic acid, glutamic acid, L-alanine, arginine, carnosine, cysteine, cystine, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, Threonine, tryptophan, tyrosine, valine, Ascorbic acid, biotin (H), carnitine, cholecalciferol, choline chloride, cyanocobalamin (B _12), ergocalciferol, folic acid, myo-inositol, menadione, nicotinamide, PABA, pantothenate, pyridoxal, pyridoxamine, pyridoxine, retinol (A ), Riboflavin (B ₂ ), thiamine (B ₁ ), 6,8 thioctic acid, alpha-tocopherol, 3-phytylmenadione (K ₁ ), tetrahydrofolic acid, polycine-derived hemin and nanopure water.
(7) L-alanine, L-arginine · HCl, L-asparagine · H ₂ O, L-aspartic acid, L-cystine · 2HCl, L-cysteine · HCl · H ₂ O, L-glutamic acid, glycine, L- Histidine · HCl · H ₂ O, L-isoleucine, L-leucine, L-lysine · HCl, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine · 2Na ⁺ · 2H ₂ O, L-valine, adenine nitrate, ATP, 2-deoxyribose, ethanolamine · HCl, D-glucose, glutathione, HEPES, hypoxanthine · Na ⁺ , linoleic acid, lipoic acid, insulin · Zn ^{+ +,} phenol red, phosphoethanolamine, putrescine · 2HCl, sodium pyruvate, Thymidine, uracil, xanthine, Na ^+, ascorbic acid Mg salt, biotin, choline chloride, D-Ca ⁺⁺ - pantothenate, folic acid, i- inositol, menadione, niacinamide, nicotinic acid, PABA, pyridoxal-HCl, pyridoxine- HCl, riboflavin, thiamine · HCl, vitamin A acetate, vitamin B12, vitamin _{D2, AgNO 3, AlCl 3 ·} 6H 2 O, Ba (C 2 H 3 O 2) 2, CdSO 4 · 8H 2 O, CoCl 2 · 6H ₂ O, Cr (SO ₄ ) ₃ · 15H ₂ O, CuSO ₄ · 5H ₂ O, Fe (NO ₃ ) ₃ · 9H ₂ O, FeSO ₄ · 7H ₂ O, GeO ₂ , H ₂ SeO ₃ , KBr, KI _{, MnCl 2 · 4H 2 O,} NaF, Na 2 SiO 3 · 9H 2 O, NaVO 3, (NH 4) 6 Mo 7 O 24 · 4H 2 O, NiSO 4 · 6 _{2 O, RbCl, SnCl 2,} TiCl 4, ZnSO 4 · 7H 2 O, ZrOCl 2 · 8H 2 O, CaCl 2, KCl, MgCl 2, MgSO 4, NaCl, NaHCO 3, Na 2 HPO 4, NaH 2 PO 4 A medium containing H ₂ O and ferric citrate chelate.   5. One or more selected from the group consisting of aspartic acid and a salt thereof and one or more selected from the group consisting of adenosine triphosphate and a salt thereof are contained in the same composition. Stabilization method.   The stabilization method according to claim 5, wherein the composition is solid.   The stabilization method according to claim 5 or 6, wherein the composition is a tablet.