Solid composition

Abstract

To provide a solid composition that contains a vitamin B12 and a specific vitamin, the solid composition less prone to a degradation of vitamins over time and having high storage stability.SOLUTION: A solid composition contains (A) at least one selected from vitamin B1, vitamin B2, vitamin B6, and ascorbic acid or salt thereof, (B) vitamin B12, and (C) taurine.SELECTED DRAWING: None

Description

Technical Field

[0007] ,

[0001] The present invention relates to a stable composition in a vitamin-containing composition in which the decrease in the content of vitamins is suppressed.

Background Art

[0002] Currently, pharmaceuticals, quasi-drugs, health foods, etc. containing multiple vitamins are commercially available. These contain different vitamins etc. according to the purpose, and are extremely useful in that they can ingest the necessary active ingredients more simply than taking multiple types of pharmaceuticals, quasi-drugs, health foods, etc. individually.

[0003] In formulating a pharmaceutical composition, the component stability of the formulation components is very important. After the formulation components are formulated, if they become unstable over time under various environmental conditions (for example, under high temperature, low temperature, exposure to light, humid environment, etc.) and their content significantly decreases, there is concern that the component may not exhibit the expected effect. In particular, in a pharmaceutical composition in which the dosage of the formulation components should be strictly controlled, a higher degree of formulation stability is required.

[0004] Water-soluble vitamins are generally known to be unstable under the influence of environmental factors such as heat and light, and tend to cause a decrease in content.

[0005] Vitamin B1s are known to have an effect of maintaining the normal functions of nerves and muscles by promoting the metabolism of carbohydrates, and are effective for fatigue recovery and stress relief, etc. (Patent Document 1).

[0006] Vitamin B2s are used as components of nutritional supplements when intake from diet is insufficient in wasting diseases etc., and also as components of preventive and therapeutic agents for diseases such as angular cheilitis, cheilitis, acute and chronic eczema, and conjunctivitis where vitamin B2 deficiency or metabolic disorders are presumed to be involved. (Patent Document 2)

[0007] Furthermore, vitamin B6 compounds are components involved in protein metabolism in the body, acting as coenzymes for amino acid decarboxylases and aminotransferases. They are widely used in pharmaceuticals, hair growth products, and health foods for physical fatigue, eye strain, and nutritional supplementation during pregnancy (Patent Document 3).

[0008] Vitamin B12 is involved in many metabolic pathways in the body and plays an important role in normal development, hematopoiesis, and myriene sheath formation in nerve tissue. It is also known to have pharmacological effects such as improving eye strain and fatigue, and is often included in multivitamins and eye drops.

[0009] However, it is widely known that these B vitamins, such as vitamin B1, vitamin B2, vitamin B6, and vitamin B12, have many stability problems, and various methods for stabilizing each B vitamin have been investigated. For example, in the case of vitamin B1, when it is combined with tocopherol succinate, methods have been disclosed to stabilize it by coating one of them with a coating agent, and methods have been disclosed to suppress the degradation of vitamin B1 over time by combining it with starch and calcium hydrogen phosphate (Patent Documents 4 and 5).

[0010] Furthermore, ascorbic acid or its salts are water-soluble vitamins and are widely known to be unstable to heat and light. For this reason, various methods for stabilizing ascorbic acid or its salts have been investigated. For example, a method of stabilizing ascorbic acid by coating it with a hydrophobic, heat-meltable lipid has been disclosed (Patent Document 6).

[0011] However, conventional methods often cannot address these issues due to limitations in formulation formulation and design. [Prior art documents] [Patent Documents]

[0012] [Patent Document 1] Japanese Patent Publication No. 2018-104393 [Patent Document 2] Japanese Patent Publication No. 11-199486 [Patent Document 3] Japanese Patent Publication No. 2015-196655 [Patent Document 4] Japanese Patent Publication No. 5-271072 [Patent Document 5] Japanese Patent Application Publication No. 9-268127 [Patent Document 6] Japanese Patent Publication No. 2001-128644 [Overview of the project] [Problems that the invention aims to solve]

[0013] The present inventors have found that when at least one selected from the group consisting of vitamin B1, vitamin B2, vitamin B6, and ascorbic acid or its salts is combined with vitamin B12, the content of each vitamin decreases over time. The object of the present invention is to provide a solid composition containing vitamin B12 and specific vitamins that can suppress the degradation of vitamins over time and has excellent storage stability. [Means for solving the problem]

[0014] As a result of various studies conducted to solve the above problems, the inventors of this invention surprisingly discovered that by incorporating taurine, a type of amino acid, the decrease in vitamin content over time can be suppressed, and thus completed the present invention.

[0015] In other words, the present invention is (1) A solid composition characterized by containing (A) at least one selected from vitamin B1, vitamin B2, vitamin B6, and ascorbic acid or a salt thereof, (B) vitamin B12, and (C) taurine. (2) Furthermore, (D) the solid composition according to (1) containing low-substituted hydroxypropyl cellulose, (3)(A) The solid composition according to (1) or (2), wherein the vitamin B1 is thiamine or a salt thereof. (4) The solid composition according to any one of (1) to (3), wherein the vitamin B2s are riboflavin or a salt thereof. (5) The solid composition according to any one of (1) to (4), wherein the vitamin B6s are pyridoxine or a salt thereof. (6) The solid composition according to any one of (1) to (5), wherein the vitamin B12s are cyanocobalamin or mecobalamin. (7) The solid composition according to any one of (1) to (6), wherein the taurine is synthetic taurine or taurine derived from aquatic products. (8) The solid composition according to any one of (1) to (7), wherein the taurine is 30 to 90% by mass based on the total mass of the composition. (9) The solid composition according to any one of (1) to (8), which is a tablet, granule, powder or capsule. It is.

Effect of the Invention

[0016] According to the present invention, it has become possible to provide a solid composition in which a decrease in the content of vitamins is suppressed.

Mode for Carrying Out the Invention

[0017] In the present invention, the "vitamin B1 group" refers to vitamin B1 or its derivatives or salts thereof. In addition to thiamine itself, its derivatives (bisthiamine, thiamine disulfide, dicyclohexyl thiamine, fursultiamine, octotiamine, ciclotiamine, bisibutiamine, bisbentiamine, prosultiamine, benfotiamine, thiamine diphosphate, etc.) and their salts (inorganic acid salts such as nitrates, hydrochlorides, sulfates, etc.) are also included, and these can be used alone or in combination of two or more. Among these, in the present invention, thiamine hydrochloride, thiamine nitrate (thiamine nitrite), bisthiamine nitrate, thiamine disulfide, thiamine dicyclohexyl sulfate ester salt, dicyclohexyl thiamine hydrochloride, fursultiamine hydrochloride, octotiamine, ciclotiamine, bisibutiamine, bisbentiamine, fursultiamine, prosultiamine, benfotiamine are preferred, thiamine nitrate (thiamine nitrite), fursultiamine hydrochloride, benfotiamine are more preferred, fursultiamine hydrochloride, thiamine nitrate (thiamine nitrite) are further preferred, and thiamine nitrate (thiamine nitrite) is particularly preferred. These vitamin B1 groups are known compounds, and commercially available ones can be used, or they can also be produced by known methods.

[0018] In the present invention, the mixing ratio of the vitamin B1 group and taurine is preferably 4 to 300 parts by mass of taurine with respect to 1 part by mass of the vitamin B1 group (when including a plurality of vitamin B1 groups, the total amount; the same shall apply hereinafter) from the effect of the stability of the vitamin B1 group, more preferably 20 to 200 parts by mass, further preferably 20 to 150 parts by mass, and particularly preferably 20 to 100 parts by mass.

[0019] In the present invention, the mixing ratio of the vitamin B1 group and low-substituted hydroxypropyl cellulose is preferably 0.5 to 50 parts by mass of low-substituted hydroxypropyl cellulose with respect to 1 part by mass of the vitamin B1 group from the effect of the stability of the vitamin B1 group, more preferably 1 to 20 parts by mass, further preferably 1 to 10 parts by mass, and particularly preferably 2 to 10 parts by mass.

[0020] The daily intake of vitamin B1 compounds in the present invention is not particularly limited and can be adjusted as appropriate depending on the intended use of the composition. For example, in the case of a composition for oral administration, the daily intake of vitamin B1 compounds is preferably 0.1 to 300 mg, more preferably 1 to 100 mg, and even more preferably 1 to 25 mg.

[0021] In the composition of the present invention, from the viewpoint of sufficiently maintaining the stability of the composition, it is preferable that vitamin B1 be contained in an amount of 0.01 to 30% by mass, more preferably 0.1 to 20% by mass, even more preferably 0.1 to 10% by mass, and particularly preferably 0.8 to 5% by mass, based on the total mass of the composition.

[0022] In the present invention, "vitamin B2 compounds" refers to vitamin B2, its derivatives, or salts thereof, and includes not only riboflavin itself, but also its derivatives (such as riboflavin phosphate, riboflavin butyrate, and flavin adenine dinucleotide) and salts thereof (such as alkali metal salts like sodium salt). In the present invention, these can be used individually or in combination of two or more. Among these, in the present invention, flavin adenine dinucleotide sodium, riboflavin, riboflavin phosphate sodium, and riboflavin butyrate are preferred, with riboflavin being particularly preferred. These vitamin B2 compounds are known compounds and may be commercially available or produced by known methods.

[0023] In the present invention, the ratio of vitamin B2 compounds to taurine is preferably 4 to 750 parts by mass, more preferably 20 to 500 parts by mass, even more preferably 20 to 300 parts by mass, and particularly preferably 40 to 250 parts by mass of taurine per 1 part by mass of vitamin B2 compounds (total amount if multiple vitamin B2 compounds are included; the same applies hereinafter) due to the effect of stabilizing vitamin B2 compounds.

[0024] In the present invention, regarding the blending ratio of vitamin B2 and low-substituted hydroxypropyl cellulose, due to the effect of the stability of vitamin B2, it is preferable that the amount of low-substituted hydroxypropyl cellulose is 0.5 to 50 parts by mass, more preferably 1 to 40 parts by mass, even more preferably 1 to 50 parts by mass, and particularly preferably 8 to 50 parts by mass per 1 part by mass of vitamin B2.

[0025] The daily intake of vitamin B2 compounds in the present invention is not particularly limited and can be adjusted as appropriate depending on the intended use of the composition. For example, in the case of a composition for oral administration, the daily intake of vitamin B2 compounds is preferably 0.1 to 100 mg, more preferably 0.5 to 45 mg, even more preferably 1 to 45 mg, and particularly preferably 2 to 15 mg.

[0026] In the present invention, from the viewpoint of sufficiently maintaining the stability of the composition, it is preferable that vitamin B2 be included in an amount of 0.01 to 30% by mass, more preferably 0.01 to 20% by mass, even more preferably 0.05 to 10% by mass, and particularly preferably 0.1 to 2.5% by mass, based on the total mass of the composition.

[0027] In the present invention, "vitamin B6 compounds" refers to vitamin B6 or its derivatives or salts thereof, and includes pyridoxine, pyridoxamine, pyridoxal itself, as well as their derivatives (such as pyridoxal phosphate) and their salts (such as alkaline earth metal salts like calcium salts; inorganic salts like hydrochloride). In the present invention, these can be used individually or in combination of two or more. Among these, pyridoxine hydrochloride and pyridoxal phosphate are preferred in the present invention, with pyridoxine hydrochloride being particularly preferred. These vitamin B6 compounds are known compounds and may be commercially available or produced by known methods.

[0028] In the present invention, the ratio of vitamin B6 compounds to taurine is preferably 4 to 750 parts by mass, more preferably 20 to 400 parts by mass, even more preferably 20 to 250 parts by mass, and particularly preferably 25 to 250 parts by mass of taurine per 1 part by mass of vitamin B6 compounds (total amount if multiple vitamin B6 compounds are included; the same applies hereinafter), due to the effect of stabilizing vitamin B6 compounds.

[0029] In the present invention, regarding the blending ratio of vitamin B6 compounds and low-substituted hydroxypropyl cellulose, due to the effect of the stability of vitamin B6 compounds, it is preferable that the amount of low-substituted hydroxypropyl cellulose is 0.5 to 50 parts by mass, more preferably 1 to 50 parts by mass, and even more preferably 10 to 50 parts by mass per 1 part by mass of vitamin B6 compounds.

[0030] The daily intake of vitamin B6 compounds in the present invention is not particularly limited and can be adjusted as appropriate depending on the intended use of the composition. For example, in the case of a composition for oral administration, the daily intake of vitamin B6 compounds is preferably 0.1 to 100 mg, more preferably 0.5 to 50 mg, even more preferably 1 to 50 mg, and particularly preferably 1 to 10 mg.

[0031] In the present invention, from the viewpoint of sufficiently maintaining the stability of the composition, it is preferable that vitamin B6 be included in an amount of 0.01 to 30% by mass, more preferably 0.1 to 20% by mass, even more preferably 0.1 to 10% by mass, and particularly preferably 0.3 to 1.8% by mass, based on the total mass of the composition.

[0032] In the present invention, "ascorbic acid or its salt" includes not only ascorbic acid itself but also its salts (alkaline earth metal salts such as calcium salts; alkali metal salts such as sodium salts, etc.), and in the present invention, these can be used individually or in combination of two or more. Among these, in the present invention, ascorbic acid and calcium ascorbate are preferred, and calcium ascorbate is particularly preferred. These ascorbic acid or its salts are known compounds and may be commercially available or produced by known methods.

[0033] In the present invention, the ratio of ascorbic acid or its salt to taurine is preferably 0.2 to 30 parts by mass, more preferably 0.3 to 20 parts by mass, even more preferably 1 to 15 parts by mass, and particularly preferably 1 to 10 parts by mass of taurine per 1 part by mass of ascorbic acid or its salt (total amount if multiple ascorbic acids or their salts are included; the same applies hereinafter), due to the effect of the stability of ascorbic acid or its salt.

[0034] In the present invention, regarding the blending ratio of ascorbic acid or its salt to low-substituted hydroxypropyl cellulose, due to the effect of the stability of ascorbic acid or its salt, the amount of low-substituted hydroxypropyl cellulose is preferably 0.1 to 40 parts by mass, more preferably 0.1 to 30 parts by mass, even more preferably 0.1 to 10 parts by mass, and particularly preferably 0.2 to 2.5 parts by mass per 1 part by mass of ascorbic acid or its salt.

[0035] The daily intake of ascorbic acid or its salt in the present invention is not particularly limited and can be adjusted as appropriate depending on the intended use of the composition. For example, in the case of a composition for oral administration, the daily intake of ascorbic acid or its salt is preferably 1 to 2,000 mg, more preferably 10 to 1,000 mg, and even more preferably 50 to 700 mg.

[0036] In the present invention, from the viewpoint of sufficiently maintaining the stability of the composition, it is preferable that ascorbic acid or a salt thereof be contained in an amount of 1 to 60% by mass, more preferably 5 to 60% by mass, and even more preferably 5 to 50% by mass, based on the total mass of the composition.

[0037] In the present invention, "vitamin B12 compounds" refers to vitamin B12 or its derivatives or salts thereof, and includes not only cyanocobalamin and hydroxocobalamin themselves, but also their derivatives (mecobalamin, deoxyadenosylcobalamin, etc.) and their salts (inorganic salts such as hydrochloride; organic salts such as acetate, etc.). In the present invention, these can be used individually or in combination of two or more. Vitamin B12 compounds all share a choline ring structure containing cobalt at the center of the molecule. In the present invention, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, mecobalamin, and hydroxocobalamin are preferred, cyanocobalamin and mecobalamin are more preferred, and cyanocobalamin is particularly preferred. These vitamin B12 compounds are known compounds and may be commercially available or produced by known methods.

[0038] In the present invention, the ratio of vitamin B12 compounds to taurine is preferably 30 to 150,000 parts by mass, more preferably 100 to 150,000 parts by mass, even more preferably 2,500 to 50,000 parts by mass, and particularly preferably 5,000 to 25,000 parts by mass of taurine per 1 part by mass of vitamin B12 compounds (total amount if multiple vitamin B12 compounds are included; the same applies hereinafter), due to the effect of stabilizing vitamin B12 compounds.

[0039] In the present invention, the ratio of vitamin B12 compounds to low-substituted hydroxypropyl cellulose is preferably 0.2 to 20,000 parts by mass, more preferably 0.6 to 15,000 parts by mass, even more preferably 15 to 5,000 parts by mass, and particularly preferably 500 to 5,000 parts by mass of low-substituted hydroxypropyl cellulose per 1 part by mass of vitamin B12 compounds, due to the effect of the stability of vitamin B12 compounds.

[0040] The daily intake of vitamin B12 compounds in the present invention is not particularly limited and can be adjusted as appropriate depending on the intended use of the composition. For example, in the case of a composition for oral administration, the daily intake of vitamin B12 compounds is preferably 1 to 5,000 μg, more preferably 1 to 1,500 μg, and even more preferably 1 to 60 μg.

[0041] In the present invention, from the viewpoint of sufficiently maintaining the stability of the composition, it is preferable that vitamin B12 be included in an amount of 0.0001 to 5% by mass, more preferably 0.001 to 1.5% by mass, and even more preferably 0.001 to 0.06% by mass, based on the total mass of the composition.

[0042] The taurine used in this invention is taurine conforming to the Japanese Pharmacopoeia or food additives, and may include synthetic taurine or extracts from aquatic products such as squid, octopus, or oysters (aquatic product-derived extracts). Preferably, it is synthetic taurine (synthetic product) or aquatic product-derived taurine, more preferably synthetic taurine. Taurine derived from bovine bile is not preferred. Taurine can be produced by known methods, or commercially available taurine can be used.

[0043] In the present invention, taurine is preferably contained in an amount of 20 to 98% by mass, more preferably 30 to 98% by mass, and even more preferably 40 to 96% by mass, based on the total mass of the composition.

[0044] The low-substituted hydroxypropyl cellulose used in the present invention is a cellulose having a very small amount of hydroxypropoxy groups in its cellulose backbone. From the viewpoint of producing a solid composition, it is preferable that the hydroxypropoxy group content is 5 to 16% by mass, more preferably 7 to 14% by mass, and even more preferably 8 to 11% by mass. Although not particularly limited, low-substituted hydroxypropyl cellulose conforming to the Japanese Pharmacopoeia or food additives is preferred, and low-substituted hydroxypropyl cellulose conforming to the Japanese Pharmacopoeia is more preferred. Low-substituted hydroxypropyl cellulose can be produced by known methods, or commercially available products can be used. In the present invention, the particle form of the low-substituted hydroxypropyl cellulose is not particularly limited, but fine powder or fibrous form is more preferred, and fibrous form is even more preferred.

[0045] In the present invention, the low-substituted hydroxypropyl cellulose is preferably contained in an amount of 1 to 30% by mass, more preferably 1 to 20% by mass, and even more preferably 3 to 20% by mass, based on the total mass of the composition.

[0046] The solid composition of the present invention is not particularly limited, but examples include pharmaceuticals, quasi-drugs, and food products. Pharmaceuticals and quasi-drugs are preferred.

[0047] The solid composition of the present invention is not particularly limited as long as it is in a dosage form as specified in the General Rules for Formulations of the Japanese Pharmacopoeia, but is preferably a tablet, powder, fine granule, granule, pill, or capsule. Tablets specified in the General Rules for Formulations of the Japanese Pharmacopoeia include orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets and dissolving tablets, film-coated tablets, sugar-coated tablets, and laminated tablets. Furthermore, the tablets may be scored, marked, or engraved to improve identification. In addition, the tablets of this formulation may be round tablets, irregularly shaped tablets, or mini-tablets.

[0048] The solid composition of the present invention may contain other commonly used active ingredients, excipients, disintegrants, binders, fluidizers, lubricants, acidulants, sweeteners, flavoring agents, cooling agents, colorants, foaming agents, surfactants, plasticizers, fragrances, coating agents, etc., within a qualitative and quantitative range that does not impair the effects of the present invention.

[0049] Other active ingredients that can be incorporated into the solid composition of the present invention include, for example, antipyretic analgesics, antihistamines, antitussives, bronchodilators, expectorants, hypnotics and sedatives, vitamins, amino acids, anti-inflammatory agents, gastric mucosal protectants, herbal medicines, Kampo prescriptions, caffeines, etc., and one or more selected from the group consisting of these may be included.

[0050] Examples of excipients that can be incorporated into the solid composition of the present invention include lactose, starches, crystalline cellulose, sucrose, sugar alcohols, calcium hydrogen phosphate, etc. Examples of disintegrants include low-substituted hydroxypropyl cellulose, sodium starch glycolate, crospovidone, carmellose, sodium carmellose, calcium carmellose, pregelatinized starch, etc. Examples of binders include hydroxypropyl cellulose, hypromellose, gelatin, pregelatinized starch, polyvinylpyrrolidone, pullulan, etc. Examples of fluidizers include light anhydrous silicic acid, hydrated silicon dioxide, etc. Examples of lubricants include sucrose fatty acid esters, hydrogenated oils, stearic acid, magnesium stearate, calcium stearate, etc.

[0051] The tablets of the present invention can be manufactured by conventional methods for manufacturing tablets. Specifically, the formulation can be manufactured by mixing the active pharmaceutical ingredient and the above-mentioned additives in a suitable mixer such as a mixer to produce a tablet mixture, and then directly compressing the mixture into tablets, or by compressing granules into tablets. The granules can be manufactured by dry granulation (slug method, roller compactor method) or wet granulation, with wet granulation being preferred. The granulation apparatus can be a roller compactor, agitation granulation, fluidized bed granulation, extrusion granulation, rolling granulation, spray granulation, etc. As a machine for compressing the tablet mixture or the granules of the mixture, a single-shot tablet press, a rotary tablet press, etc., can be used. [Examples]

[0052] The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to these examples.

[0053] (Preparation of solid composition) (Examples 1-10, Comparative Examples 1-6) After weighing each raw material component according to the formulation composition shown in Table 1, they were mixed uniformly. The mixture was then kneaded in a mortar with an appropriate amount of water and ethanol, granulated, and thoroughly dried. The entire mixture was then passed through a sieve (mesh size 710 μm) to obtain granules, which were then compressed into tablets.

[0054] [Table 1]

[0055] Stability test (change in content) For the obtained tablets, the content of thiamine nitrate, riboflavin, pyridoxine hydrochloride, and cyanocobalamin was measured at the start of the test and in samples stored for one day under 65°C conditions, and the remaining percentage was calculated. The results are shown in Table 2.

[0056] [Table 2]

[0057] As shown in Table 2, the remaining vitamin B group in Comparative Example 1, which contained only low-substituted hydroxypropyl cellulose and no taurine, and in Comparative Examples 2 to 5, which also contained no taurine, were all 90% or less. On the other hand, in Example 1, which contained only taurine, it was clear that the remaining vitamin B group was dramatically improved compared to Comparative Examples 1 to 3. Furthermore, in Examples 2 to 8, which contained both taurine and low-substituted hydroxypropyl cellulose, the remaining vitamin B group content was 90% or higher in all cases, demonstrating that the remaining content could be further improved. In Comparative Example 6, which contained calcium ascorbate, the residual rate of cyanocobalamin was 80% or less. In Examples 9 and 10, which contained both taurine and low-substituted hydroxypropyl cellulose, the residual rate of cyanocobalamin was 90% or more, demonstrating a dramatic improvement in the residual rate of cyanocobalamin. [Industrial applicability]

[0058] According to the present invention, a solid composition containing vitamins and taurine can be provided that exhibits excellent storage stability.

Claims

1. A solid composition comprising (A) at least one selected from vitamin B1, vitamin B2, vitamin B6, and ascorbic acid or a salt thereof, (B) vitamin B12, and (C) taurine.

2. The solid composition according to claim 1 , further comprising (D) low-substituted hydroxypropyl cellulose.

3. 3. The solid composition according to claim 1 or 2, wherein the vitamin B1 group (A) is thiamine or a salt thereof.

4. 3. The solid composition according to claim 1 or 2, wherein the vitamin B2 compound (A) is riboflavin or a salt thereof.

5. The solid composition according to claim 1 or 2, wherein the vitamin B6 (A) is pyridoxine or a salt thereof.

6. The solid composition according to claim 1 or 2, wherein the vitamin B12 (B) is cyanocobalamin or mecobalamin.

7. The solid composition according to claim 1 or 2, wherein the taurine (C) is synthetic taurine or marine-derived taurine.

8. The solid composition according to claim 1 or 2, wherein the taurine (C) is 30 to 90% by mass based on the total mass of the composition.

9. 3. The solid composition according to claim 1 or 2, which is in the form of a tablet, granule, powder or capsule.

10. A method for stabilizing (A) at least one selected from vitamins B1, B2, B6, and ascorbic acid or a salt thereof, and / or (B) vitamin B12 in a solid composition containing (A) at least one selected from vitamins B1, B2, B6, and ascorbic acid or a salt thereof, and (B) vitamin B12, by incorporating (C) taurine.