KR20070032752A - vitamin preparations - Google Patents

Abstract

To provide a more stable vitamin preparation comprising tocopherol or succinic acid salts thereof and vitamin B ₁ or salts thereof, to suppress the decrease in the content of succinate tocopherol or salts thereof, tocopherol or salts thereof, vitamin B ₁ or A vitamin preparation comprising the salt and a basic inorganic compound having a cost of about 3 ml / g or more.

Description

Vitamin preparation {VITAMIN PREPARATIONS}

The present invention relates to a vitamin preparation containing tocopherol succinate or salt thereof and vitamin B ₁ or salts thereof used in fields such as food or pharmaceuticals.

Japanese Unexamined Patent Publication No. 63-243034 discloses a sticking or capping produced when tableting by formulating a predetermined amount or more of calcium silicate in formulating a low melting point material represented by dl-α-tocopherol acetate (oil phase at room temperature). It is described that it is possible to obtain a solid agent having sufficient hardness to prevent the damage.

Japanese Unexamined Patent Application Publication No. 5-271072 discloses that, in a vitamin preparation containing succinic acid tocopherol or its salt (solid at room temperature) and vitamin B ₁ or its salt, the succinic acid tocopherol or its salt is poor in stability and content decrease occurs. It is. Therefore, a method for obtaining a stable vitamin preparation by coating at least one with a coating agent in producing a vitamin preparation comprising tocopherol succinate or its salt and vitamin B ₁ or a salt thereof as a solution is described.

Conventionally, in order to formulate a component having poor stability in the formulation and causing a decrease in content, for example, in the case of pure tablets, each component group is prepared separately to reduce contact, or to separate them into nucleated tablets or multilayer tablets. Or in the case of dragee preparation, it was common to mix | blend with dragee layer. However, nucleated tablets and the like have a high manufacturing cost, and the compounding of sugar layer has a problem in that the variation in content becomes large.

Therefore, there is a need for the development of a more stable vitamin preparation containing tocopherol succinate or its salts and vitamin B ₁ or salts thereof, which is simpler than the prior art, and which suppresses the effect required for commercialization and a decrease in the content of succinate tocopherol or its salts. have.

The present inventors have conducted various studies and studies on the preparation of a vitamin preparation comprising tocopherol or its salt and a vitamin B class ₁ or salt thereof, and the basic inorganic compound having a cost of about 3 ml / g or more in the preparation. The present invention was completed by discovering that tocopherol succinate or its salt was stably maintained over a long period of time unexpectedly, and that a vitamin preparation having more desirable properties could be obtained as a product. Among them, the natural type (d-type) succinic acid d-α-tocopherol was first found to be very poor in stability due to mixing with vitamin B class ₁ or its salts. A highly stable vitamin formulation containing tocopherols was completed.

That is, the present invention

(1) a vitamin preparation comprising a mixture of tocopherol or a salt thereof, vitamin B ₁ or a salt thereof and a basic inorganic compound having a cost of about 3 ml / g or more,

(2) The vitamin preparation according to the above (1), wherein the vitamin B ₁ or a salt thereof is an active vitamin B ₁ derivative or a salt thereof,

(3) The vitamin preparation according to (1), comprising 10 parts by weight or more of a basic inorganic compound having a cost of about 3 ml / g or more based on 100 parts by weight of tocopherol or its salt,

(4) the vitamin preparation according to the above (1), wherein the succinic acid tocopherol or its salt is d-type,

(5) a vitamin preparation comprising particles containing a succinic acid tocopherol or a salt thereof and a basic inorganic compound having a cost of about 3 ml / g or more, and particles containing a vitamin B class ₁ or salt thereof,

(6) a method for stabilizing succinate tocopherol or its salt, comprising combining a basic inorganic compound having a cost of about 3 ml / g or more in a formulation containing tocopherol or its salt and vitamin B ₁ or its salt, and

(7) The vitamin preparation according to (2), wherein the active vitamin B ₁ derivative is a vitamin B ₁ derivative having an SS bond.

Tocopherols of succinic acid tocopherol or salts thereof used in the present invention include, for example, α-tocopherol. As a salt of such succinate tocopherol or its salt, salt of alkaline earth metals, such as calcium and barium, is mentioned, for example. Specific examples of succinate tocopherol or salts thereof include succinate tocopherol calcium, succinic acid dl-α-tocopherol calcium, succinic acid d-α-tocopherol calcium, succinic acid dl-α-tocopherol or succinic acid d-α-tocopherol, and the like. Type succinic acid tocopherol or its salt (for example, succinic acid d-α-tocopherol, succinic acid d-α-tocopherol calcium, etc.) is preferable. Such succinic acid tocopherol or its salt is, for example, US Patent No. 2407726, Japanese Patent Publication No. 41-1618, Japanese Patent Publication No. 42-17822, Japanese Patent Publication No. 43-29005, Japanese Patent Publication No. 49-32055 And Japanese Patent Application Laid-Open No. 60-4185 and the like can be produced by a known technique. Further, dispersible powders of succinic acid tocopherol or salts thereof, such as those described in JP-A-61-60619, can also be used as the raw material of the present invention.

Examples of the vitamin B ₁ or salts thereof used in the present invention include salts with inorganic acids (eg, hydrochloric acid, nitric acid, phosphoric acid, and the like) of thiamine, such as thiamine hydrochloride and thiamine nitrate, or an active vitamin B ₁ derivative or salt thereof. Can be mentioned. Such active type vitamin B ₁ derivatives include, for example, compounds having SS (disulfide) bonds (e.g., prosultiamine, fursultiamine, octothiamine, thiamine disulfide, thiamine disulfide) , Bisbentiamine, bisbutythiamine, bisibtiamine and the like), cicothiamine, benfothiamine, cocarboxylase and the like. In addition, as the salt of these active-form vitamin B ₁ derivatives includes, for example, a salt with an inorganic acid such as hydrochloric acid, nitric acid, phosphoric acid. Specific examples may be mentioned salts of the active-form vitamin B ₁ derivatives such as thiamine hydrochloride greener alcohol, hydrochloric acid thiamine Francisco, phosphoric thiamine disulfide, thiamine di cetyl sulfate ester salts, thiamine hydrochloride disabled automatically and the like. Among the active vitamin B ₁ derivatives or salts thereof, preferably compounds having a SS (disulfide) bond or salts thereof, specifically, prosulfamine, fursulthiamine, fursulthiamine hydrochloride, octothiamine, thiamine disulfide, Thiamine phosphate disulfide, bisbenthiamine, bisbutythiamine, bisibthiamine, etc. are used. These may be used alone or in combination.

The cost of the basic inorganic compound having a cost of about 3 ml / g or more is specifically about 3-20 ml / g, preferably about 3-15 ml / g, more preferably about 3.5-12 ml / g ( In addition, this value is a characteristic value of the raw material for formulation, and does not represent the cost of the basic inorganic compound in the final formulation in the case of a formulation to which external force is applied in the production of tablets, particles, and the like). The basic inorganic compound which has such a cost can be obtained by selecting suitably from a commercial item. In addition, the basic inorganic compound having such a cost has a large specific surface area (nitrogen adsorption method (BET type), and the specific surface area is about 50 to about 400 m 2 / g, preferably about 50 to about 200 m 2 / g, more preferably About 80 to about 150 m 2 / g), which is often a fine particle and / or a porous structure. The basic inorganic compound having a cost of about 3 ml / g or more has a basic alkalinity when the inorganic compound is dissolved or suspended in distilled water at a concentration of 4% by weight, and preferably has a pH greater than 7 and no greater than 12, more preferably. Preferably it refers to a compound having a pH of about 8 to 11, more preferably a pH of about 8 to 10. Such basic inorganic compounds include, for example, calcium salts such as calcium carbonate, calcium silicate, special calcium silicate (e.g., Flolite RE [trade name, manufactured by Tokuya Soda Co., Ltd.), calcium oxide, calcium sulfate, or calcium chloride) Alkali metal salts, such as magnesium salts corresponding to these, or sodium salts, such as sodium carbonate or sodium hydrogencarbonate, are alkali metal salts, Preferably it is an alkali metal salt, More preferably, a calcium salt, Specifically, a special calcium silicate salt ( For example, Flolite RE [trade name, manufactured by Tokuya Soda Co., Ltd.], calcium carbonate or calcium silicate, more preferably special calcium silicate (e.g., Flolite RE [trade name, manufactured by Tokuya Soda Co., Ltd.], etc.) Can be mentioned. These can also be used individually or in combination. The term "specific volume" refers to the "volume occupied by an object of unit mass (1 g)" and is equal to the inverse of the density. In other words, "cost" means "inverse of volume density". In the case of powder, voids exist within the structure of the powder particles and between the particles. When the volume including the void volume is the volume of the powder, the value obtained by dividing the volume by the mass of the powder is "cost". It is also called "cost" and "appearance".

By blending a basic inorganic compound having such a specific cost, it is possible to suppress a decrease in the content of succinic acid tocopherol or its salt, thereby obtaining a highly stable vitamin preparation.

The content ratio of succinic acid tocopherol or its salt in the vitamin preparation of the present invention is about 0.1 to 80% by weight, preferably about 0.4 to 50% by weight, more preferably about 1 to 40% by weight. In addition, the content ratio of vitamin B ₁ or its salt in the vitamin preparation of the present invention is about 0.01 to 85% by weight, preferably about 0.1 to 50% by weight, more preferably about 0.5 to 40% by weight. In the vitamin preparation of the present invention, the amount of succinate tocopherol or its salt to be blended in one formulation is, for example, in the range of about 1 to 300 mg, and preferably in the range of about 2 to 100 mg, for example. In addition, in the vitamin preparation of the present invention, the amount of the vitamin B class ₁ or its salt to be blended in one formulation is, for example, in the range of about 0.1 to 300 mg, preferably about 1 to 200 mg, more preferably about It is the range of 1-100 mg.

In the vitamin preparation of the present invention, the blending ratio of vitamin B class ₁ or its salt with respect to succinate tocopherol or its salt is about 0.001 to 100 parts by weight, preferably about 0.01 to 50 parts by weight based on 1 part by weight of tocopherol or its salt. Part, more preferably about 0.1 to 10 parts by weight.

In the vitamin preparation of the present invention, the compounding amount of the basic inorganic compound having a cost of about 3 ml / g or more for tocopherol or succinic acid is about 10 parts by weight or more, based on 100 parts by weight of tocopherol or its salt, for example. About 10-150 weight part, Preferably it is about 10-120 weight part.

The particle formulated with acid-tocopherol or blended with the salt particles and vitamin B ₁ acids or their salts for use in the case of a formulation which will be described later is a state or containing containing a basic inorganic compound, the cost is at least about 3 ml / g In either case, it may be coated with a coating agent. Examples of the coating agent include water-soluble celluloses such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose (eg, TC-5 (trade name, manufactured by Shin-Etsu Chemical Co., Ltd.)) and methyl cellulose; Coating agents soluble only in acidic regions such as polyvinyl acetal diethylamino acetate; Enteric bases such as hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate or acrylic copolymer; Water-insoluble bases such as ethylcellulose; Also gelatin; Shellac; Sodium alginate; Waxes; Fatty acids (eg, stearic acid or palmitic acid, etc.) and salts thereof (eg, salts with sodium or potassium, etc.); Fatty alcohols (eg, stearin alcohol or cetyl alcohol); Lipids such as fatty acid glycerin esters and hydrogenated oils thereof (eg, hardened cottonseed oil, hardened castor oil, hardened soybean oil, etc.); Polyglycerin fatty acid esters (eg, penta stearate (tetra) glyceride, mono (tetra) glyceride stearate or hexa (tetra) glyceride behenic acid); Hot liquid obtained by heating and solidifying starch (eg, corn starch, potato starch, rice starch, etc.); Talc (including sterile talc); Precipitated calcium carbonate and the like. In addition, the coating agent includes a coating aid (e.g., polyethylene glycol (e.g., polyethylene glycol 6000, etc.), an extender (e.g., sugars such as lactose, granulated sugar, starch, etc.), a coloring agent (e.g., tar color, caramel, etc.). , Bengal, titanium oxide, riboflavin and the like), a copper agent (for example, sweetener, flavor, etc.) may be appropriately added.

In addition, as a component (active ingredient) used in the manufacture of various kinds of medicines, quasi-drugs, food, etc., tocopherol succinate or salts thereof and components except vitamin B class ₁ or salts thereof are added at the time of preparation of the preparation of the present invention. can do. Such components include, for example, vitamin B ₂ and its derivatives or salts thereof, vitamin B ₆ and its derivatives or salts thereof, vitamin C and its derivatives or salts thereof, vitamin D and its derivatives or salts thereof, and vitamin B ₁₂ And vitamins such as derivatives or salts thereof, and compositions containing these vitamins. Specifically, for example, retinol acetate, retinol palmitate, vitamin A oil, cod liver oil, rape oil, ergocalcinphenol, which are described in the pharmaceutical preparation instructions ('91, Pharmacopoeia, p. 579-596) and the like. Cholecalcinphenol, acetic acid d-α-tocopherol acetate, dl-α-tocopherol acetate, d-α-tocopherol, dl-α-tocopherol, flavinadenindinucleotide sodium, folic acid, riboflavin, riboflavin sodium phosphate, lacboflavin hydrochloride, hydrochloric acid Pyridoxine, pyrophosphate hydrochloride, hydrocobalamin hydrochloride, hydrocobalamate acetate, cyanocobalamin, hydroxylcobalamin, mecobalamin (methylcobalamin), nicotinic acid, nicotinic acid amide, panthenol, calcium pantothenate, sodium pantothenate, potassium aspartate, biotin, magnesium asparta Etc. Mixture, Inositol hexanicotinate, Ursodesoxycholic acid, L-cysteine hydrochloride, L-cysteine, orotin acid, γ-orizanol, glycerol acid Calcium, calcium gluconate, calcium lactate, anhydrous calcium phosphate, calcium hydrogen phosphate, glucronolactone, glucuronic acid amide, sodium chondroitin sulfate, processed Daesan, carrot, Yulmu rice, etc. Vitamins such as caffeine, anhydrous caffeine, carnitine, mineral groups (e.g. magnesium, calcium, iron, etc.), herbal medicines (e.g., antler powder, carrot extract, sulfur, etc.), antacids (e.g. For example, components, such as synthetic hydrotalcite etc., may be contained in the formulation of this invention. These components can be suitably added 1 type or 2 or more types by an appropriate amount or a suitable compounding ratio in the range which does not interfere with this invention.

For example, the vitamin preparation of the present invention contains, for example, about 0.1 to 80% by weight, preferably about 0.2 to 50% by weight, of vitamin B ₆ and its derivatives or salts thereof (e.g. pyridoxine hydrochloride, pyridoxalate phosphate, etc.) It can also be made into a formulation. Likewise, in the vitamin preparations of the invention, for example, vitamin B ₁₂ and its derivatives or salts thereof (e.g., hydrocobalamin hydrochloride, hydrocobalamate acetate, cyanocobalamin, hydroxylcobalamin, mecobalamin (methylcobalamin) and the like) About 0.00001 to 20% by weight, preferably about 0.0001 to 10% by weight, more preferably about 0.0005 to 2% by weight, about 0.1 to 30% by weight of γ-orizanol, preferably about 0.2 to 20% by weight, Folic acid may be blended in an amount of about 0.005 to 10% by weight, preferably about 0.005 to 5% by weight, more preferably about 0.01 to 3% by weight.

The combination of the active ingredients in the vitamin preparation of the present invention includes, for example, succinate tocopherol or salts thereof and vitamin B ₁ or salts thereof (preferably an active vitamin B ₁ derivative or salt thereof having an SS bond). , Also at least one or more of vitamin B ₆ and derivatives thereof or salts thereof (preferably pyridoxine hydrochloride, pyridoxalate) and vitamin B ₁₂ and derivatives thereof or salts thereof (preferably mecobalamin or hydroxylcobalamin), Preferably, a vitamin preparation containing all of the above components is preferable. In these active ingredients, preferably about 1 to 40% by weight of succinate tocopherol or its salt and vitamin B class ₁ or its salt (preferably Preferably about 1 to 40% by weight of the active vitamin B ₁ derivative or salt thereof having an SS bond, and vitamin B ₆ and its derivative or salt thereof (preferably About 0.2 to 50% by weight of pyridoxine hydrochloride and pyridoxal phosphate) and about 0.0005 to 2% by weight of vitamin B ₁₂ and its derivatives or salts thereof (preferably mecobalamin or hydroxylcobalamin).

When preparing the formulations of the present invention, additives used in the formulations in amounts that will not impair the effects of the invention, such as excipients (e.g. starches such as lactose, cornstarch, crystalline cellulose, granulated sugar, porous Materials such as hard silicic anhydride), binders (e.g., alpha starch, gelatin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, pullulan, gum arabic powder, etc.), disintegrants (e.g., carboxymethyl cellulose calcium) , Croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, partially alpha starch, etc., lubricants (e.g. magnesium stearate, calcium stearate, etc.), colorants (e.g. tar colors, caramels) , Bengal, titanium oxide, riboflavin, etc.), copulation agents (e.g., sweeteners, fragrances, etc.), coatings selected from the coating and coating aids (preferably hydroxypropyl Methyl cellulose (e.g. TC-5 [trade name, manufactured by Shin-Etsu Chemical Co., Ltd.], etc.), polyethylene glycol (e.g., polyethylene glycol 6000, etc.), talc (including sterile talc), precipitated calcium carbonate, etc. It may be compounded or coated in the formulation.

The preparation of the vitamin preparation of the present invention can be prepared by, for example, mixing a basic inorganic compound having a cost of about 3 ml / g or more with succinate tocopherol or its salt, vitamin B class ₁ or its salt, and mixing it by a method known per se. Can be. Further, tocopherol succinate or its salt and vitamin B ₁ acids or salts thereof at the time of the formulation is preferably in the form of powder. If necessary, the granules may be kneaded and / or granulated to form granules, or the obtained granules may be compression molded to form tablets. Tablets compression-molded by mixing particles containing a basic inorganic compound having a cost of about 3 ml / g or more, succinate tocopherol or a salt thereof, and particles containing vitamin B ₁ are preferred. The granulation method for obtaining the particles can be assembled using, for example, a general preparation device such as an electric granulator, a stirring granulator, a fluid granulator, a centrifugal electric granulator, a centrifugal electric fluid granulator, an electric fluid granulator and an extrusion granulator. At the time of kneading or spraying at the time of granulation, a suitable solvent (for example, water, ethanol, acetone or a mixture thereof) can be used. Tablets obtained by compression molding may be subjected to lower treatment, mixing dispersion treatment, mixing treatment, syrup treatment and the like, if desired.

The vitamin preparation of this invention can be obtained by the manufacturing method shown next, for example. (1) Tocopherol succinate or its salts are dried by adding γ-orizanol, vitamin B ₆ and derivatives thereof or salts thereof (e.g., pyridoxine, etc.), basic inorganic compounds, excipients and disintegrants having a cost of about 3 ml / g or more. The mixture is mixed in the wet state, and then granulated, and if desired, the coating is added or coated after the assembly if desired. ② Separately mixed in dry or wet state with the addition of vitamin B class ₁ or its salts and excipients, and then assembled. Further, if desired, powdered mecobalamin, which is coated during or after assembling with a folate-dispersed coating agent, and ③ (1) and (2) above the average particle diameter of about 300 to 500 µm, mixed and ground with an excipient such as cornstarch, The vitamin preparation of the present invention can be obtained by mixing with an excipient, disintegrant and lubricant to form a tablet. If desired, a coating agent containing hydroxypropyl methyl cellulose or / and polyethylene glycol may be used, and then a mixed solution consisting of a coating agent containing precipitated calcium carbonate, a binder, a coloring agent, and the like, and a dispersing agent comprising a coating agent and the like may be used. It can be used as sugar-coated tablets by mixing dispersion treatment, mixing treatment, and syrup treatment.

For the formulation of mecobalamin, it is preferable to use a powder which is ground and mixed with an excipient such as mecobalamin or cornstarch without substantially containing water, without granulation or suspending as described above for stabilization thereof. In this way, it can mix | blend in a formulation, suppressing degradation of mecobalamin to the minimum. In addition to the formulation of the present invention, such a method can be widely used for any mecobalamin-containing solid preparation, such as a preparation of mecobalamin sweet rice.

The vitamin preparation of the present invention is not limited to the above-mentioned tablets, and solid preparations such as powders, granules, pills, capsules, oral disintegrating agents and the like are prepared according to conventional methods. Preferred are tablets. The size of the tablet is not particularly limited, but is preferably about 3 to 5 mm in thickness and about 5 to 10 mm in diameter. These solid preparations may coat white sugar or granulated sugar on the surface of the preparation. Furthermore, the preparation of the present invention may be used to form nucleated tablets or laminated tablets by the general method, or may be prepared by adding the preparation of the present invention to the components of the sugar layer. The vitamin preparation of the present invention thus obtained may be used as a product as it is, but an appropriate amount may be appropriately added during the preparation of various medicines, quasi-drugs, foods and the like containing succinic acid tocopherol or its salts and vitamin B ₁ or salts thereof. It may be.

The vitamin preparation of the present invention exerts the effects as vitamin E and vitamin B ₁ similarly to conventional succinate tocopherol or its salts and vitamin B ₁ or the vitamin preparations containing the salts thereof. Mammals, birds, reptiles, etc.) can be used safely as a drug, quasi-drug, or food. For example, peripheral circulatory disorders in humans (e.g., stiff shoulders or nape, swelling of the limbs, coldness, frostbite, etc.), menopausal disorders (e.g. stiffness of the shoulders or nape, swelling of the limbs; Neuralgia, myalgia, arthritis, back pain, stiff shoulders, constipation, eye fatigue, physical fatigue, illness during or after illness, pregnancy and lactation, scurvy, moller-boarlow disease and capillary bleeding 0.1 to 300 mg of tocopherol or its salt, preferably 1 to 300 mg and vitamin B class ₁ or its salt, 0.1 to 300 mg, preferably 1 to 200 mg, more preferably Is administered orally to the vitamin preparation of the present invention containing 1 to 100 mg divided into 1 to 3 times a day.

Embodiment of the invention

Hereinafter, the present invention will be described in more detail with reference to Examples, Reference Examples, and Experimental Examples, but the present invention is not limited thereto.

EXAMPLE

Example 1

200 g of succinic acid d-α-tocopherol, basic calcium silicate with basic cost of 10 ml / g (specific surface area 120 m 2 / g (BET type)) (folite RE [trade name, manufactured by Tokuya Soda Co., Ltd.]) , 40 g of γ-orizanol, 40 g of low-substituted hydroxypropyl cellulose and 22.3 g of crystalline cellulose were prepared using 4 wt% hydroxypropyl cellulose (HPC-L) using a vertical granulator (FM-VG-10, manufactured by Powderex). ) 543 ml of aqueous solution and 400 ml of purified water (Group E). On the other hand, 1091.6 g of fursulthiamine hydrochloride, 1000 g of pyridoxine hydrochloride, 111 g of hard silicic anhydride (Sirisia 320 [trade name, manufactured by YKK F Co., Ltd.)) and 282.6 g of crystalline cellulose were prepared in a fluidized bed granulator (Furex Corporation FD). -3S) was used to assemble 1270 ml of 4% by weight aqueous solution of hydroxypropyl cellulose (HPC-L) in which 4 g of folic acid was dispersed (T group). Each of the two kinds of granulated powders obtained (Group E and Group T) was stipulated to an average particle diameter of about 400 µm using a power mill (P-3S manufactured by Showa Kikawa Co., Ltd.), followed by 362 g of Group E and Take 508 g of T group and 60 g of mecobalamin (20 times dispersible powder of cornstarch). 11.1 g of hard silicic anhydride (Sirisia 320 [trade name, manufactured by WK-K Corporation), 66.6 g of low-substituted hydroxypropyl cellulose (L-HPC-31), 65.64 g of crystalline cellulose, and 6.66 g of magnesium stearate are mixed. Then, a pure tablet having a diameter of 8 mm (6.5 R) and a thickness of 4.42 mm was manufactured with a rotary purifier (Kikusui Seisakusho Collect 19K). Subsequently, after mixing and dispersing using 417.6 g of a mixed solution in which sterile talc, precipitated calcium carbonate, granulated sugar, gum arabic powder and titanium oxide were dissolved or dispersed in purified water and 376 g of a dispersing agent consisting of sterile talc and gum arabic powder, The kneading treatment is performed using 369.6 g of the mixed solution, and sugar coating is performed by using a sugar pan (Kikusui Seisakusho 10-inch pan) on which sugar is prepared using 190 g of syrup solution containing granulated sugar and riboflavin. Dragee 3 tablets The blending component and blending amount of a sugar are shown in the Example 1 column of [Table 1a-b].

Example 2

The dragee is obtained by the method similar to Example 1 using the compounding component shown in the Example 2 column of Table 1a-b. The compounding component and compounding ratio which are shown in the Example 2 column of Table 1a-b are the values of sugar tablet 3 sugar.

Example 3

Using the compounding component shown in the Example 3 column of Table 1a-b, sugar-coated tablets are obtained in the same manner as in Example 1. The compounding component and compounding ratio which are shown in the Example 3 column of Table 1a-b are the values of sugar tablet 3 sugar. In addition, the cost of calcium carbonate is 4 ml / g.

Example 4

The dragee is obtained by the method similar to Example 1 using the compounding component shown in the Example 4 column of [Table 1a-b]. The compounding component and compounding ratio which are shown in the Example 4 column of Table 1a-b are the values of sugar tablet 3 sugar.

Example 5

The dragee is obtained by the method similar to Example 1 using the compounding component shown in the Example 5 column of Table 1a-b. The compounding component and compounding ratio which are shown in the column of column 5 of Table 1a-b are the values of sugar tablet 3 sugar.

Example 1 [mg] Example 2 [mg] Example 3 [mg] Example 4 [mg] Example 5 [mg] E group Succinic acid d-α-tocopherol 100 100 100 100 100 Pyridoxine hydrochloride - - - 100 - Special calcium silicate (Florite RE [brand name]) 50 25 - 50 15 Calcium carbonate - - 50 - - γ-orizanol 10 - 10 10 - Low Substituted Hydroxypropyl Cellulose (L-HPC) 10 10 10 12 10 Crystalline cellulose 5.57 5.65 5.57 19 60 Hydroxypropyl Cellulose (HPC-L) 5.43 4.35 5.43 9 10 Purified water (130.32 μl) (104.4 μl) (130.32 μl) (148.1 μl) (90 μl) Subtotal (solid content) 181 145 181 300 195 T group Pursulthiamine Hydrochloride 109.16 109.16 109.16 109.16 109.6 Pyridoxine hydrochloride 100 100 100 - - Phosphate pyridoxal - - - - 60 Folic acid 0.4 0.4 0.4 0.4 One γ-orizanol - 10 - - 10 Hard anhydrous silicic acid (Sirisia 320 [brand name]) 11.1 11.1 11.1 - - Crystalline cellulose 28.26 28.06 28.26 37.44 52.64 Hydroxypropyl Cellulose (HPC-L) 5.08 5.28 5.08 3 7.2 Purified water (121.92 μl) (126.72 μl) (121.92 μl) (57 μl) (112.8 μl) Subtotal (solid content) 254 264 254 150 240 mix E Military Sizing Powder 181 145 181 300 195 T Group Sizing Powder 254 264 254 150 240 Mecobalamin (corn powder 20 times dispersible powder) 30 30 30 30 - Mecobalamin Mixed Grinding Powder * - - - - 30 Hard anhydrous silicic acid (Sirisia 320 [brand name]) 5.55 5.55 5.55 5 5.4 Low Substituted Hydroxypropyl Cellulose (L-HPC-31) 33.3 33.3 33.3 26 27 Crystalline cellulose 32.82 58.82 32.82 11.4 38.28 Magnesium Stearate 3.33 3.33 3.33 2.6 4.32 Pure refined sum 540 540 540 525 540 Mixture Titanium oxide 6.6 6.6 6.6 6.6 7.2 Sterile talc 43.8 43.8 43.8 43.8 47.8 Precipitated calcium carbonate 72 72 72 72 78.6 Arabian Rubber Powder 18.6 18.6 18.6 18.6 20.3 Gran New 159 159 159 159 173.7 Purified water (80.8 μl) (80.8 μl) (80.8 μl) (80.8 μl) (88.2 μl) Subtotal (solid content) 300 300 300 300 327.6

Example 1 [mg] Example 2 [mg] Example 3 [mg] Example 4 [mg] Example 5 [mg] Dispersant Sterile talc 176.4 176.4 176.4 176.4 130.6 Arabian Rubber Powder 3.6 3.6 3.6 3.6 3.3 Crystalline cellulose - - - - 33.5 Subtotal (solid content) 180 180 180 180 167.4 Syrup Gran New 74.83 74.83 74.83 74.83 74.83 Riboflavin 0.17 0.17 0.17 0.17 0.17 Purified water (37.43 μl) (37.43 μl) (37.43 μl) (37.43 μl) (37.43 μl) Subtotal (Solid) _ 75 75 75 75 75 Party total 1095 1095 1095 1080 1110

※ Mecobalamin mixed pulverized powder: 20-fold dispersion powder mixed with mecobalamin 1.5 mg, cyclia 0.9 mg, corn starch 27 mg and crystalline cellulose 0.6 mg

Comparative Example 1

Using the compounding component shown in the comparative example 1 in Table 2, sugar dragee is obtained by the method similar to Example 1. The biggest difference between Comparative Example 1 and Example 1 is that instead of the special calcium silicate (Florite RE [trade name, manufactured by Tokuya Soda Co., Ltd.]) in Group E of Example 1, it is neutral and costs 7 ml / g (ratio The point which uses hard silicic acid anhydride (Sirisia 320 [brand name, WK-F company make]) whose surface area is 300 m <2> / g (BET type)) is mentioned. In addition, the compounding component and compounding ratio which are shown in the column of the comparative example 1 in Table 2 are the values of sugar tablet 3 sugar.

Comparative Example 2

Using the compounding component shown in the comparative example 2 in Table 2, sugar dragee is obtained by the method similar to Example 1. The biggest difference between Comparative Example 2 and Example 1 is that meta, which is basic and has a cost of 2.5 ml / g instead of the special calcium silicate (Florite RE [trade name, manufactured by Tokuya Soda Co., Ltd.]) in Group E of Example 1 The point which uses magnesium silicate (Nicillin [brand name, manufactured by Fuji Chemical Co., Ltd.]) is mentioned. In addition, the compounding component and compounding ratio which are shown in the column of the comparative example 2 in Table 2 are the values of sugar tablet 3 sugar.

Comparative Example 1 [mg] Comparative Example 2 [mg] E group Succinic acid d-α-tocopherol 100 100 Hard anhydrous silicic acid (Sirisia 320 [brand name]) 50 - Magnesium metasilicate aluminate (nocirine [brand name]) - 50 γ-orizanol - 10 Low Substituted Hydroxypropyl Cellulose (L-HPC) - 10 Crystalline cellulose 4 5.57 Hydroxypropyl Cellulose (HPC-L) 8 5.43 Purified water (125.3 μl) (130.32 μl) Subtotal (solid content) 162 181 T group Pursulthiamine Hydrochloride 109.16 109.16 Pyridoxine hydrochloride 100 100 Folic acid 0.4 0.4 γ-orizanol 10 - Hard anhydrous silicic acid (Sirisia 320 [brand name]) - 11.1 Crystalline cellulose 27.74 28.26 Hydroxypropyl Cellulose (HPC-L) 13.7 5.08 Purified water (214.6 μl) (121.92 μl) Subtotal (solid content) 261 254 mix E Military Sizing Powder 162 181 T Group Sizing Powder 261 254 Mecobalamin (corn powder 20 times dispersed ingredient) 30 30 Hard anhydrous silicic acid (Sirisia 320 [brand name]) 5.55 5.55 Low Substituted Hydroxypropyl Cellulose (L-HPC-31) 41.7 33.3 Crystalline cellulose 35.65 32.82 Magnesium Stearate 4.1 3.33 Pure refined sum 540 540 Mixture Titanium oxide 6.6 6.6 Sterile talc 43.8 43.8 Precipitated calcium carbonate 72 72 Arabian Rubber Powder 18.6 18.6 Gran New 159 159 Purified water (80.8 μl) (80.8 μl) Subtotal (solid content) 300 300 Dispersant Sterile talc 176.4 176.4 Arabian Rubber Powder 3.6 3.6 Subtotal (solid content) 180 180 Syrup Gran New 74.83 74.83 Riboflavin 0.17 0.17 Purified water (37.43 μl) (37.43 μl) Subtotal (Solid) _ 75 75 Party total 1095 1095

Experimental Example 1

The dragees obtained by Examples 1, 2, 3, Comparative Example 1 and Comparative Example 2 were stored in a glass bottle for 4 weeks under conditions of 40 ° C, and then succinic acid as a high-performance liquid chromatograph for each dragee. The content of d-α-tocopherol is measured. Table 3 shows the results of calculating the residual ratio for the sugar-coated tablets (initials) before the storage test for 4 weeks from the content obtained by the measurement. In the vitamin preparations of the present invention represented by Examples 1, 2 and 3, there was no decrease in the content of succinic acid d-α-tocopherol, but in the vitamin preparations of the control groups represented by Comparative Examples 1 and 2, succinic acid d A decrease in the content of -α-tocopherol was confirmed.

Thus, it can be seen that excellent stability can be obtained by blending a basic inorganic compound having a cost of about 3 ml / g or more with succinic acid d-α-tocopherol.

Conduct / Comparative Example Number Survival rate (%) Example Comparative example One 2 3 One 2 40 ℃ 4 weeks 100.1 99.7 99.8 93.5 92.5

The vitamin preparation of the present invention is stable and the content decrease of tocopherol succinate or salt thereof is suppressed, and the change over time in the quality is extremely small.

Claims (6)

A vitamin preparation comprising a succinic acid tocopherol or salt thereof, vitamin B class ₁ or salt thereof, and a basic inorganic compound having a cost of about 3 ml / g or more. The vitamin preparation according to claim 1, wherein the vitamin B ₁ or salt thereof is an active vitamin B ₁ derivative or salt thereof. The vitamin preparation according to claim 1, wherein the vitamin preparation comprises 10 parts by weight or more of a basic inorganic compound having a cost of about 3 ml / g or more based on 100 parts by weight of succinate tocopherol or its salt. The vitamin preparation according to claim 1, wherein the succinate tocopherol or salt thereof is form d. A vitamin preparation comprising particles containing a succinic acid tocopherol or a salt thereof and a basic inorganic compound having a cost of about 3 ml / g or more, and particles containing a vitamin B ₁ or a salt thereof. A method for stabilizing succinate tocopherol or its salt, comprising combining a basic inorganic compound having a cost of about 3 ml / g or more to a formulation containing succinic tocopherol or its salt and vitamin B ₁ or its salt.