JP2011063580A - Composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition which has reduced smell originated from a processed garlic product or controls the lowering in the content of vitamin B groups, vitamin E or gamma-oryzanol, and has good quality stability. <P>SOLUTION: The composition comprises 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 products, vitamin B groups, vitamin E and gamma-oryzanol. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a novel composition with improved stability of processed garlic, vitamin B group, vitamin E and gamma oryzanol.

  Ingredients such as processed garlic, vitamin B group, vitamin E, and gamma oryzanol have various pharmacological and physiological effects and are widely used in pharmaceuticals, quasi drugs, cosmetics, etc. is there. The processed garlic is known to have a fatigue recovery effect, a nourishing tonic and the like, and is widely used as a component of a nourishing tonic. Vitamin is an essential nutrient and is used to treat its deficiency. For vitamin B group, vitamin E is used to relieve various symptoms such as neuralgia, muscle pain, joint pain, numbness of limbs, and eye strain. Is used to relieve various symptoms such as stiff shoulder / neck streaks, numbness / coldness in limbs and peripheral limbs in peripheral blood circulation disorders. Gamma oryzanol is a substance present in rice bran oil, rice germ oil, corn oil and other cereal nut oils, and is a mixture of ferulic acid (3-methoxy-4-hydroxycinnamic acid) ester of triterpene alcohol. (Non-patent document 1), growth promoting action, autonomic dysfunction alleviating action, gonadal stimulating action, sebum secretion promoting action, blood flow promoting action, skin temperature raising action, antioxidant action, ultraviolet absorption action, tyrosinase activity inhibiting action It is also known to have a high safety.

  However, processed garlic, vitamin B group, vitamin E, and gamma-oryzanol are all unstable, and quality stability over time becomes a problem in compositions containing these components. As for the processed garlic, unpleasant odor peculiar to garlic is generated with the passage of time, and the content of vitamin B group, vitamin E, and gamma oryzanol is lowered with the passage of time due to decomposition and component change. Generation of an unpleasant odor and a decrease in the content of components cause deterioration in the feeling of use and uniformity of the composition, respectively, and consequently deteriorate the quality of the composition and the like, thereby reducing its commercial value.

Many attempts have been made to improve the stability of processed garlic, vitamin B group, vitamin E, and gamma oryzanol. For example, for the problem of generation of unpleasant odor with the passage of time in processed garlic, a method of leaving garlic for 1 week to 1 year under low oxygen or anoxic conditions at 1 to 40 ° C. (Patent Document) 1) A method in which garlic is kept at 20 ° C. or higher for 7 days or more and then treated at a hydrostatic pressure of 300 MPa or higher under a temperature condition of 0 to 65 ° C. (Patent Document 2), a solid preparation containing activated garlic and activated carbon A solution means such as a method of storing in a closed container (Patent Document 3) has been proposed. In addition, with respect to problems such as degradation and component changes with time in vitamin B group, vitamin E, and gamma-oryzanol, a method of combining vitamin B1 and crospovidone in a weight ratio of 1: 1 to 1:10 (patent Reference 4), a granulated granule containing 75 to 97% by weight of vitamin B6 is blended so that the total content of vitamin B1, vitamin B12 and other active ingredients is 65 to 80% by weight in the uncoated tablet. A method of making a tablet (Patent Document 5), a method of filling a polyethylene naphthalate container with an oil-soluble vitamin-containing solution such as vitamin E (Patent Document 6), a gamma-oryzanol-containing aqueous solution, a water-soluble antioxidant and / or water-soluble Solution means such as a method (Patent Document 7) in which a reactive colorant is contained has been proposed. However, these methods are not always versatile, such as taking too much time to process, requiring storage in a specific container, requiring a specific amount of a specific component, and being applicable only to aqueous solutions. There is no such thing.
As described above, known methods for stabilizing ingredients such as processed garlic, vitamin B group, vitamin E, and gamma-oryzanol have not been satisfactory.

International Publication No. WO2004 / 077963 Pamphlet JP-A-6-335360 JP 2009-78981 A JP 2002-302446 A Japanese Patent Laid-Open No. 9-169651 JP 2003-321353 A JP 7-258165 A

FRAGRANCE JOURNAL, 3, p71-77, 1998

  An object of the present invention is to provide a composition with good quality stability in which the odor derived from processed garlic is suppressed, or the decrease in the content of vitamin B group, vitamin E or gamma oryzanol is suppressed.

As a result of intensive studies in view of such circumstances, the present inventors have surprisingly found that at least one selected from the group consisting of aspartic acid and its salt is processed garlic, vitamin B group, vitamin E, and gamma oryzanol. It has been found that it has an effect of improving the stability by suppressing the generation of the odor and the decrease in the content.
Furthermore, when the present inventors examined the pharmacological action of the combination of each of the above components, surprisingly, one or more selected from the group consisting of aspartic acid and its salts, processed garlic, and vitamin B group It has also been found that an excellent eye strain recovery action can be obtained by using one or more selected from the group.

  That is, the present invention is a composition comprising 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, vitamin B group, vitamin E and gamma oryzanol. Is to provide.

  In addition, the present invention coexists one or more selected from the group consisting of processed garlic, vitamin B group, vitamin E and gamma oryzanol, and one or more selected from the group consisting of aspartic acid and salts thereof. One or more stabilization methods selected from the group consisting of processed garlic, vitamin B group, vitamin E, and gamma oryzanol are provided.

Furthermore, the present invention provides the following components (A) and (B)
(A) one or more selected from the group consisting of aspartic acid and salts thereof;
(B) one or more selected from the group consisting of processed garlic and vitamin B group;
It provides a composition for improving eye strain containing

According to the present invention, the odor derived from the processed garlic product that is generated over time is suppressed, or the decrease in the content of one or more selected from the group consisting of vitamin B group, vitamin E, and gamma oryzanol is suppressed. It is possible to provide a composition having a high commercial value and a high quality stability with improved stability over time and improved stability over time.
Moreover, according to the stabilization method of the present invention, it is possible to suppress the odor derived from processed garlic, or to suppress a decrease in the content of one or more selected from the group consisting of vitamin B group, vitamin E and gamma oryzanol, The stability of these components can be improved, and the commercial value of a composition containing these components can be increased.
Furthermore, the composition of the present invention comprising at least one 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, It has a fatigue recovery action and can be suitably used for the treatment and relaxation of eye strain (particularly, accommodation eye strain).

  In the present specification, “stabilization” refers to suppression of odor derived from processed garlic and / or suppression of decrease in content of one or more selected from the group consisting of vitamin B group, vitamin E and gamma oryzanol.

In the present invention, as “aspartic acid”, any of L-aspartic acid and D-aspartic acid may be used, and further a mixture thereof may be used. In the present invention, L-aspartic acid is preferred.
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 calcium salt and magnesium salt, and the like. It can be used alone or in combination of two or more. In the present invention, potassium salt, calcium salt and magnesium salt are preferred.

  In the present invention, the “one or more selected from the group consisting of aspartic acid and its salts” includes a free form of aspartic acid, a potassium salt of aspartic acid, a calcium salt of aspartic acid, and a magnesium salt of aspartic acid. One or more selected from the group consisting of a potassium salt of aspartic acid and a magnesium salt of aspartic acid is more preferable, and a mixture of a potassium salt of aspartic acid and a magnesium salt of aspartic acid is more preferable. Particularly preferred is an equivalent mixture of an acid potassium salt and an aspartic acid magnesium salt (potassium aspartate / magnesium equivalent mixture). These aspartic acids and salts thereof are known compounds, which may be commercially available, or can be produced by known methods.

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 contained. Is more preferable, and it is especially preferable to contain 1.5-50 mass%.

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

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

  In addition, although the shape of the composition of this invention is not specifically limited, In the case where the composition of this invention is an aspect containing at least a garlic processed material, it is preferable that it is a solid composition. As described in the test examples below, the composition of the present invention is said to suppress the odor derived from the processed garlic in the case of a solid composition such as a solid preparation in which the odor derived from the processed garlic is particularly problematic. Has an excellent effect.

  The content of the processed garlic product 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 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 the present invention, the “vitamin B group” includes vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9 and vitamin B12, which are used alone or in combination of two or more. Can be used. In the present invention, the vitamin B group is preferably at least one selected from the group consisting of vitamin B1, vitamin B2, vitamin B6 and vitamin B12, and from the group consisting of vitamin B1, vitamin B2, vitamin B6 and vitamin B12. More preferably, it is at least two selected, more preferably at least three selected from the group consisting of vitamin B1, vitamin B2, vitamin B6 and vitamin B12, and vitamin B1, vitamin B2, vitamin B6 and vitamin B12 The combination of is particularly preferable. As will be apparent from the test examples described later, among the above vitamin B groups, vitamin B12 has a problem in content stability, and the present inventors are selected from the group consisting of aspartic acid and salts thereof. One or more have been found to stabilize vitamin B12 particularly significantly.

  The content of the vitamin B group 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 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 a salt thereof in the composition of the present invention and the vitamin B group is not particularly limited, but the stabilizing action and the eye strain recovery action of the vitamin B group From the viewpoint of the above, the total amount of one or more kinds selected from the group consisting of aspartic acid and its salt is preferably 0.00000005 to 3000 parts by weight, more preferably 0.0000005 to 300 parts by weight. 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 selected from the group consisting of sultiamine and benfotiamine are preferred, and benfotiamine is particularly preferred. These vitamin B1s are known compounds, and commercially available products may be used, or they can be produced by known methods.

  The content of vitamin B1 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 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.
Further, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof and vitamin B1 in the composition of the present invention is not particularly limited, but the viewpoint of the stabilizing action of vitamin B1 and the action of restoring eye strain Therefore, Vitamin B1 0.00005 to 500 parts by mass is preferable, 0.0005 to 100 parts by mass is more preferable, and 0.001 with respect to 1 part by mass in total of at least one selected from the group consisting of aspartic acid and salts thereof. -50 mass parts is particularly preferred.

  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 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 its salt in the composition of the present invention and vitamin B2 is not particularly limited, but the viewpoint of the stabilizing action of vitamin B2 and the action of restoring eye strain From 0.05 to 200 parts by mass, more preferably 0.0005 to 50 parts by mass, more preferably 0.001 to 50 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. ˜25 parts by mass is particularly preferred.

  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 and nicotinic acid amide 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 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 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 salts thereof in the composition of the present invention is not particularly limited, but the viewpoint of the stabilizing action of vitamin B3 and the action of restoring eye strain From 0.005 to 200 parts by mass of vitamin B3 is preferable, and 0.005 to 100 parts by mass is more preferable, relative to 1 part by mass in total of at least one selected from the group consisting of aspartic acid and salts thereof. -50 mass parts is particularly preferred.

  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 preferred. 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 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, 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.
In addition, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof and vitamin B5 in the composition of the present invention is not particularly limited, but the viewpoint of stabilizing action of vitamin B5 and recovery of eye strain From 0.001 to 200 parts by mass of vitamin B5, more preferably 0.001 to 50 parts by mass, and more preferably 0.01 to 200 parts by mass with respect to a total of 1 part by mass of at least one selected from the group consisting of aspartic acid and salts thereof. ˜25 parts by mass is particularly preferred.

  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 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.
In addition, the mass ratio of at least one selected from the group consisting of aspartic acid and salts thereof and vitamin B6 in the composition of the present invention is not particularly limited, but the viewpoint of the stabilizing action of vitamin B6 and the action of restoring eye strain From 0.001 to 1000 parts by weight of vitamin B6, more preferably 0.0005 to 300 parts by weight, and more preferably 0.001 to 1 part by weight in total of at least one selected from the group consisting of aspartic acid and salts thereof. -50 mass parts is particularly preferred.

  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 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.
In addition, the mass ratio of at least one selected from the group consisting of aspartic acid and its salt and vitamin B7 in the composition of the present invention is not particularly limited, but the viewpoint of the stabilizing action of vitamin B7 and the action of restoring eye strain Therefore, Vitamin B7 0.000000005 to 10 parts by mass is preferable, 0.000001 to 5 parts by mass is more preferable, and 0.00001 to 1 part by mass in total of at least one selected from the group consisting of aspartic acid and salts thereof. ˜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 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, 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 viewpoint of stabilizing action of vitamin B9 and recovery action of eye strain Therefore, vitamin B9 is preferably 0.00005-100 parts by mass, more preferably 0.00001-10 parts by mass, more preferably 0.00001 with respect to 1 part by mass in total of at least one selected from the group consisting of aspartic acid and salts thereof. ˜5 parts by mass is particularly preferred.

  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 selected from the group consisting of hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin 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 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, vitamin B12 per day is about 0.0001 to 50 mg, preferably about 0.001 to 50 mg, more preferably about 0.0005 to 10 mg, and further preferably about 0.001. 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 viewpoint of the stabilizing action of vitamin B12 and the action of restoring eye strain Therefore, Vitamin B12 is preferably 0.0000005 to 5 parts by weight, more preferably 0.000005 to 5 parts by weight, and more preferably 0.00001 to 1 part by weight in total of at least one selected from the group consisting of aspartic acid and salts thereof. ˜1 part by mass is particularly preferred.

  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 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 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 at least one selected from the group consisting of aspartic acid and its salt in the composition of the present invention and vitamin E content is not particularly limited, but from the viewpoint of the stabilizing action of vitamin E, aspartic acid and its Vitamin E 0.0001 to 1000 parts by weight is preferable, 0.001 to 200 parts by weight is more preferable, and 0.01 to 100 parts by weight is particularly preferable with respect to 1 part in total of at least one selected from the group consisting of salts. .

  “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 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 salts thereof in the composition of the present invention and the content of gamma-oryzanol is not particularly limited, but from the viewpoint of the stabilizing action of gamma-oryzanol, aspartic acid and its It is preferable to contain 0.0001 to 150 parts by mass of gamma-oryzanol, more preferably 0.001 to 20 parts by mass, with respect to 1 part in total of at least one selected from the group consisting of salts. It is particularly preferable to contain ~ 5 parts by mass.

One preferred embodiment of the present invention includes a composition containing 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. It is done. The composition of this aspect has an excellent eye strain recovery action, as specifically disclosed in the following test examples.
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, It is more preferable that it is an embodiment containing two or more kinds of vitamin B groups selected from vitamin B6 and vitamin B12, and in addition to processed garlic, three or more kinds selected from vitamin B1, vitamin B2, vitamin B6 and vitamin B12 are further added. 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.
When the composition of the present invention is a composition containing at least one selected from the group consisting of aspartic acid and salts thereof, processed garlic, and vitamin B group, the mass content of processed garlic and vitamin B group The ratio is not particularly limited, but from the viewpoint of an eye strain recovery action, 0.0000002 to 1500 parts by mass of vitamin B group is preferable and 0.000005 to 100 parts by mass is more preferable with respect to a total of 1 part by mass of the processed garlic. 0.00005 to 25 parts by mass is particularly preferable.

  In the composition of the aspect containing both the processed garlic and the vitamin B group, the odor derived from the processed garlic is suppressed, so that it is easy to use and the stability of the vitamin B group is good. Therefore, it can be suitably used for treatment and alleviation of eye strain (particularly, accommodation 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.), disodium adenosine triphosphate, ursodeoxycholic acid, amino acids (L-cysteine hydrochloride, L-cysteine, L-lysine lysine, L-arginine hydrochloride) , L-methionine, aminoethylsulfonic acid, etc.), orotic acid, calcium salts (such as calcium glycerophosphate, calcium gluconate, precipitated calcium carbonate, calcium lactate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, calcium citrate), gluc Acids (glucuronolactone, glucuronic acid amide, etc.), chondroitin sulfate sodium, carrot (carrot), Yokuinin (Yokujin), Yakukoku, Rokujo (deer moth), Hampi (anti-nasal), gou (oxen), royal jelly, seisei ( Yellow spirit), kokushi (coconut), boray (oyster), caffeine (caffeine, anhydrous caffeine, sodium benzoate caffeine, etc.), inositol, carnitine chloride, rutin, decongestant (epinephrine, epinephrine hydrochloride, hydrochloric acid) Ephedrine, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, dl-methylephedrine hydrochloride), neostigmine methyl sulfate, anti-inflammatory / convergent components (epsilon-aminocaproic acid, allantoin, berberine chloride, sulfuric acid) Ruberine, sodium azulenesulfonate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate, lysozyme chloride, etc.), antihistamines (diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), 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.), al Kill polyaminoethyl glycine, boric acid, etc. are mentioned, These can be used individually or in combination of 2 or more types. In the present invention, it is preferable to contain calcium salts.

  Specific examples of Kampo prescriptions include Kamishoyosan (Kamisusan), Hotu 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, Tablets are more preferable, and sugar-coated tablets are particularly preferable. As specifically disclosed in Test Examples to be described later, the present inventors have one or more selected from the group consisting of aspartic acid and salts thereof having excellent binding ability, and a solid composition as a binder. It was found that it can be used as a pharmaceutical additive in 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 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, 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 a pharmaceutical, a quasi-drug, a cosmetic, a food, and the like. 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 the present invention, excellent eye strain is achieved 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. Based on the recovery action, it can be suitably used as a composition for improving eye strain. 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.

  In the stabilization method of the present invention, one or more selected from the group consisting of processed garlic, vitamin B group, vitamin E, and gamma-oryzanol and one or more selected from the group consisting of aspartic acid and salts thereof are coexistent. “Sake” means to create a state in which both components are present in the same system (eg, 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, at least one selected from the group consisting of processed garlic, vitamin B group, vitamin E, and gamma-oryzanol is allowed to coexist with one or more selected from the group consisting of aspartic acid and its salt. As an aspect, for example, an aspect in which one or more selected from the group consisting of processed garlic, vitamin B group, vitamin E, and gamma-oryzanol and one or more selected from the group consisting of aspartic acid and salts thereof are mixed; garlic One or more selected from the group consisting of processed products, vitamin B group, vitamin E and gamma oryzanol, and one or more selected from the group consisting of aspartic acid and its salt (particularly solid composition) And the like.

Specific examples of the stabilization method of the present invention include the following methods (a) to (p).
(A) One or more types selected from the group consisting of aspartic acid and salts thereof are allowed to coexist with the processed garlic product, and a method for suppressing odors derived from the processed garlic product.
(B) One or more types selected from the group consisting of aspartic acid and salts thereof, and the garlic processed product are mixed, and the method for suppressing the odor derived from the garlic processed product.
(C) One or more types selected from the group consisting of aspartic acid and salts thereof, and a garlic processed product are contained in the same composition, and a method for suppressing odors derived from the garlic processed product.
(D) One or more types selected from the group consisting of aspartic acid and salts thereof, and a garlic processed product are contained in the same composition, and the method for suppressing the odor of the composition.

(E) One or more types selected from the group consisting of aspartic acid and salts thereof and the vitamin B group are allowed to coexist, and the method for stabilizing the vitamin B group.
(E-i) A method for stabilizing vitamin B1, characterized by causing vitamin B1 to coexist with at least one member selected from the group consisting of aspartic acid and salts thereof.
(E-ii) A method for stabilizing vitamin B2, characterized by causing vitamin B2 to coexist with at least one selected from the group consisting of aspartic acid and salts thereof.
(E-iii) A method for stabilizing vitamin B6, comprising causing vitamin B6 to coexist with at least one member selected from the group consisting of aspartic acid and salts thereof.
(E-iv) A method for stabilizing vitamin B12, wherein vitamin B12 is allowed to coexist with at least one selected from the group consisting of aspartic acid and salts thereof.

(F) One or more types selected from the group consisting of aspartic acid and salts thereof, and the vitamin B group are mixed, and the method for stabilizing the vitamin B group.
(F-i) A method for stabilizing vitamin B1, comprising mixing at least one selected from the group consisting of aspartic acid and salts thereof and vitamin B1.
(F-ii) A method for stabilizing vitamin B2, comprising mixing at least one member selected from the group consisting of aspartic acid and salts thereof and vitamin B2.
(F-iii) A method for stabilizing vitamin B6, comprising mixing at least one member selected from the group consisting of aspartic acid and salts thereof and vitamin B6.
(F-iv) A method for stabilizing vitamin B12, comprising mixing at least one member selected from the group consisting of aspartic acid and salts thereof and vitamin B12.

(G) One or more types selected from the group consisting of aspartic acid and a salt thereof, and the vitamin B group are contained in the same composition, and the method for stabilizing the vitamin B group.
(G-i) A method for stabilizing vitamin B1, wherein one or more members selected from the group consisting of aspartic acid and salts thereof and vitamin B1 are contained in the same composition.
(G-ii) A method for stabilizing vitamin B2, wherein one or more members selected from the group consisting of aspartic acid and salts thereof and vitamin B2 are contained in the same composition.
(G-iii) A method for stabilizing vitamin B6, wherein one or more members selected from the group consisting of aspartic acid and salts thereof and vitamin B6 are contained in the same composition.
(G-iv) A method for stabilizing vitamin B12, comprising one or more members selected from the group consisting of aspartic acid and salts thereof and vitamin B12 in the same composition.

(H) One or more types selected from the group consisting of aspartic acid and salts thereof and the vitamin B group are contained in the same composition, and a method for suppressing a decrease in the content of the vitamin B group in the composition .
(H-i) A method for suppressing a decrease in the content of vitamin B1 in a composition, comprising at least one member selected from the group consisting of aspartic acid and a salt thereof and vitamin B1 in the same composition .
(H-ii) A method for suppressing a decrease in the content of vitamin B2 in a composition, wherein one or more members selected from the group consisting of aspartic acid and salts thereof and vitamin B2 are contained in the same composition. .
(H-iii) One or more kinds selected from the group consisting of aspartic acid and salts thereof, and vitamin B6 are contained in the same composition, and a method for suppressing a decrease in the content of vitamin B6 in the composition .
(H-iv) One or more kinds selected from the group consisting of aspartic acid and salts thereof, and vitamin B12 are contained in the same composition, and a method for suppressing a decrease in the content of vitamin B12 in the composition .

(I) A method for stabilizing vitamin E, comprising causing vitamin E to coexist with at least one selected from the group consisting of aspartic acid and salts thereof.
(J) A method for stabilizing vitamin E, comprising mixing one or more members selected from the group consisting of aspartic acid and salts thereof with vitamin E.
(K) One or more types selected from the group consisting of aspartic acid and salts thereof, and vitamin E are contained in the same composition, and the method for stabilizing vitamin E is characterized.
(L) One or more types selected from the group consisting of aspartic acid and salts thereof, and vitamin E are contained in the same composition, and a method for suppressing a decrease in vitamin E content in the composition.

(M) A method for stabilizing gamma oryzanol, characterized by causing gamma oryzanol to coexist with at least one member selected from the group consisting of aspartic acid and salts thereof.
(N) A method for stabilizing gamma oryzanol, comprising mixing at least one member selected from the group consisting of aspartic acid and salts thereof and gamma oryzanol.
(O) A method for stabilizing gamma oryzanol, comprising incorporating at least one selected from the group consisting of aspartic acid and a salt thereof and gamma oryzanol in the same composition.
(P) A method for suppressing a decrease in the content of gamma-oryzanol in a composition, comprising incorporating at least one selected from the group consisting of aspartic acid and a salt thereof and gamma-oryzanol in the same composition.

  Moreover, in the said stabilization method, it stabilizes by making 1 or more types chosen from the group which consists of aspartic acid and its salt, a garlic processed material, a vitamin B group, vitamin E, and gamma oryzanol coexist. It is preferable to do this.

  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.

[Example 1]
Aspartic acid salt (L-aspartate potassium / magnesium: Alps Yakuhin Kogyo Co., Ltd.) 2400 g, processed garlic (oxoamidin powder: RIKEN CHEMICAL INDUSTRY 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 suspension consisting of 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 was used. 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 Example 1 except that crystalline cellulose (Theoras PH-101: Asahi Kasei Chemicals Corporation) was used instead of the salt of aspartic acid.

[Test Example 1] Evaluation of suppression of odor derived from processed garlic product 180 tablets each obtained in Example 1 and Comparative Example 1 under conditions of 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: No 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 1.

  From the result of Table 1, in the tablet of Comparative Example 1 containing no 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 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, according to this invention, the composition excellent in the quality by which the smell derived from a garlic processed product was suppressed can be provided.

[Test Example 2] Evaluation of content stability of vitamin B group, vitamin E and gamma-oryzanol 180 tablets each obtained in Example 1 and Comparative Example 1 were packaged using glass bottles and metal caps, 40 ° C, 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 respectively determined according to Benfoth described in the Japanese Pharmacopoeia Pharmaceutical Standards 1997. Thiamine Determination Method, Fifteenth Amendment Japanese Pharmacopoeia Quantitative Method of Riboflavin as described in each Pharmaceutical Article, Fifteenth Amendment Japanese Pharmacopoeia Quantitative method of pyridoxine hydrochloride described in each Pharmaceutical Article, Fifteenth Amendment Japanese Pharmacopoeia Pharmaceutical 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 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 2 to 7.

  From the results of Tables 2 to 7, 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, in the tablet of Example 1 containing potassium L-aspartate / magnesium, almost no decrease in content was observed after storage for 4 months, and the content stability was excellent. Therefore, it became clear that potassium L-aspartate / magnesium has a stabilizing action of benfotiamine, riboflavin, pyridoxine hydrochloride, cyanocobalamin, dl-α-tocopherol calcium succinate and gamma-oryzanol. In particular, the stabilizing effect on cyanocobalamin was remarkable.

From the above test results, at least one selected from the group consisting of aspartic acid and its salts has a stabilizing action of vitamin B group such as vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin E, and gamma-oryzanol. As a result, it became clear that content stability over time was increased.
Therefore, according to the present invention, it is possible to provide a composition having excellent quality over time and excellent quality in vitamin B group, vitamin E, and gamma oryzanol.

[Example 2]
Aspartic acid salt (L-aspartate potassium / magnesium: Alps Yakuhin Kogyo Co., Ltd.) 2400 g, processed garlic (oxoamidin powder: RIKEN CHEMICAL INDUSTRY 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 granules RIKEN 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 Example 2 except that crystalline cellulose (Ceolus PH-101: Asahi Kasei Chemicals Corporation) was used instead of the aspartic acid salt.

[Test Example 3] 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 Example 2 and Comparative Example 2 was measured. Specifically, the tablets of Example 2 and Comparative Example 2 were each 20 tablets for each tableting pressure condition, the tablet hardness was measured for each tablet with a tablet hardness meter (PTB-311E: PHARMATE), and the average The value was calculated. The results are shown in Table 8.

  From the results of Table 8, the tablet of Example 2 containing the salt of aspartic acid has a hardness of about 2 under any tableting pressure conditions as compared with the tablet of Comparative Example 2 not containing the salt of aspartic acid. 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 4] 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 9. 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 9, in the single administration group of components (A) and (B), about 1.2 to 1.3 times the enhancement of ciliary muscle contraction force was observed compared to before drug administration. 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, the composition of the present invention in an embodiment 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 processed garlic and vitamin B group, improves eye strain. It was revealed that the composition can be suitably used as an application composition.

  According to the present invention, a product with good quality stability over time, in which the odor derived from processed garlic which is generated over time is suppressed, or the decrease in the content of vitamin B group, vitamin E or gamma oryzanol is suppressed A highly valuable composition can be provided, and can be used in the pharmaceutical industry, the cosmetics industry, the food industry, and the like.

Claims (5)

  A composition comprising 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, vitamin B group, vitamin E, and gamma oryzanol.   The composition according to claim 1, wherein the vitamin B group is at least one selected from the group consisting of vitamin B1, vitamin B2, vitamin B6, and vitamin B12.   The processed garlic is processed potato, the vitamin B group is at least one selected from the group consisting of benfotiamine, riboflavin, pyridoxine hydrochloride and cyanocobalamin, and vitamin E is dl-α-tocopherol calcium succinate. 3. The composition according to 1 or 2.   The composition according to any one of claims 1 to 3, which is a solid composition.   The composition according to any one of claims 1 to 4, which is a tablet.