JP2000247879A - Vitamin preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a stable vitamin preparation by including a tocopherol succinate, vitamin B1, and a specific basic inorganic compound so as to suppress the tocopherol succinate. SOLUTION: This vitamin preparation is obtained by including (A) pref. 0.1-80 wt.%; of a tocopherol succinate (e.g. α-tocopherol) or a salt thereof (e.g. d-α-tocopherol succinate calcium salt), (B) pref. 0.01-85 wt.% of vitamin B1 or a salt thereof (e.g. prosultiamine, fursultiamine, octotiamine, tiamine phosphate disulfide), and (C) pref. >=10 pts.wt., based on 100 pts.wt. of the ingredient A, of a basic inorganic compound >=3 mL/g in specific volume (e.g. calcium carbonate, calcium silicate); wherein the weight ratio B/A is pref. 0.001-100.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates are used in fields such as food or pharmaceuticals, to a vitamin formulation comprising tocopherol succinic acid or a salt thereof and the vitamin B ₁ class or a salt thereof.

[0002]

2. Description of the Related Art In formulating a low melting point substance represented by dl-α-tocopherol acetate (oil at room temperature),
Japanese Patent Application Laid-Open No. Sho 63-2 discloses that by adding calcium silicate in a certain amount or more, a solid agent having sufficient hardness can be obtained without sticking or capping at the time of tableting.
43034. JP-A-5-271072
The, in the vitamin formulation comprising a tocopherol succinate or a salt thereof (solid at room temperature) and vitamin B ₁ class or a salt thereof, the stability of tocopherol succinate or a salt thereof is poor, it is described that the content reduction occurs I have. Therefore, a method as solving means, in producing the vitamin preparations containing a combination of tocopherol or its succinate and vitamin B ₁ class or a salt thereof, to obtain a stable vitamin preparations by coating the at least one with a coating agent Is described. Conventionally, the stability is poor in the formulation,
In order to formulate components that cause a decrease in content, for example, in the case of uncoated tablets, each component group is separately manufactured to reduce contact, or both are separated into a dry coated tablet or a multilayer tablet, and further, sugar-coated tablets In the case of preparations, they were generally incorporated into the sugar coating layer. However, dry coated tablets and the like have a drawback in that the production cost is high, and the content in the sugar coating layer varies widely.

[0003]

[0005] Accordingly, comprising tocopherol or a salt of succinic acid and vitamin B ₁ class or a salt, yet simpler than the prior art, effective and necessary for commercialization, tocopherol or its succinate There has been a demand for the development of a more stable vitamin preparation which suppresses a decrease in the content of vitamin C.

[0004]

The present inventors have SUMMARY OF THE INVENTION As a result of performing various studies and research on the production of vitamin preparations containing tocopherol or its succinate and vitamin B ₁ class or a salt thereof, in the formulation By blending a basic inorganic compound having a specific volume of about 3 ml / g or more, tocopherol succinate or a salt thereof is stably retained for an unexpectedly long period of time, and a vitamin preparation having more desirable properties as a product can be obtained. That is, the present invention has been completed. In particular, it was found for the first time that the natural (d-form) d-α-tocopherol succinate becomes very poor in stability when mixed with vitamin B ₁ or a salt thereof, and such natural (d) A highly stable vitamin preparation containing d-α-tocopherol succinate in the body was completed.
That is, the present invention is (1) tocopherol succinate or a salt thereof, vitamin B ₁ class or vitamin preparations salt thereof and specific volume are obtained by blending a basic inorganic compound is about 3 ml / g or more, (2) Vitamin B _The specific volume is about 3 ml / g or more with respect to 100 parts by weight of the vitamin preparation according to the above (1), wherein the class ₁ or a salt thereof is an active vitamin B ₁ derivative or a salt thereof, and (3) 100 parts by weight of tocopherol succinate or a salt thereof. And (4) the vitamin preparation according to (1), wherein tocopherol succinate or a salt thereof is in d-form, and (5) and characterized in that it contains a grain blended with basic inorganic compound tocopherol succinate or its salts and specific volume is about 3 ml / g or more, and a particle containing a combination of vitamin B ₁ class or a salt thereof Vitamin preparations that, succinic acid, which comprises blending (6) Class ₁ tocopherol succinate or a salt thereof and vitamin B or basic inorganic compound specific volume is about 3 ml / g or more preparations containing the salts thereof The present invention relates to the method for stabilizing tocopherol or a salt thereof, 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.

The tocopherol succinate or a salt thereof used in the present invention includes, for example, α-
And tocopherol. Examples of such salts of tocopherol succinate or salts thereof include salts of alkaline earth metals such as calcium and barium.
Specific examples of tocopherol succinate or a salt thereof include tocopherol calcium succinate, dl succinate
-Α-tocopherol calcium, d-α-tocopherol calcium succinate, dl-α-tocopherol succinate or d-α-tocopherol succinate, etc., preferably d-form tocopherol succinate or a salt thereof
(Examples: d-α-tocopherol succinate, d-succinate
α-tocopherol calcium, etc.). Such tocopherol succinate or a salt thereof is described in, for example, U.S. Pat. No. 2,407,726, JP-B-41-1618,
It can be manufactured by a known technique described in JP-B-42-17822, JP-B-43-29005, JP-B-49-32055, JP-B-60-4185 and the like. Also,
It is also possible to use a dispersible powder of tocopherol succinate or a salt thereof as described in JP-A-61-60619 as a raw material of the present invention.

Examples of the vitamin B ₁ or its salt used in the present invention include a salt of a thiamine such as thiamine hydrochloride and thiamine nitrate with an inorganic acid (eg, hydrochloric acid, nitric acid, phosphoric acid and the like) or an active vitamin B ₁ derivative. Or salts thereof. Examples of such an active vitamin B ₁ derivative include compounds having an SS (disulfide) bond (eg, prosultiamine, fursultiamine, octtiamine,
Thiamine disulfide, Thiamine phosphate disulfide,
Bisbenthiamin, bisbutiamine, bisibutiamine, etc.), sicotiamine, benfotiamine, cocarboxylase and the like. Examples of the salt of such an active vitamin B ₁ derivative include salts with inorganic acids such as hydrochloric acid, nitric acid and phosphoric acid. Active vitamin B ₁
Specific examples of the salt of the derivative include fursultiamine hydrochloride, sicotiamine hydrochloride, thiamine disulfide phosphate, thiamine dicetyl sulfate, disetiamine hydrochloride and the like. Of the active vitamin B ₁ derivatives or salts thereof, compounds having an SS (disulfide) bond or salts thereof are preferably prosultiamine, fursultiamine, fursultiamine hydrochloride, octtiamine, Thiamine disulfide, thiamine phosphate disulfide, bisbenthamine, bisbutiamine, bisibutiamine and the like are used. These can be used alone or in combination.

The specific volume of the basic inorganic compound having a specific volume of about 3 ml / g or more is specifically about 3-20 ml / g, preferably about 3-15 ml / g, more preferably about 3.5-3.5 ml / g. 12 ml / g (this value is a characteristic value as a raw material for formulation, and is a basic inorganic content in the final formulation in the case of a formulation to which external force is applied such as tableting or granulation). It does not indicate the specific volume of the compound.) The basic inorganic compound having such a specific volume can be obtained by appropriately selecting a commercially available product. The basic inorganic compound having such a specific volume has a large specific surface area (a specific surface area of about 50 to about 400 m ² / g, preferably about 5 m ² / g by nitrogen adsorption method (BET method)).
0 to about 200 m ² / g, more preferably about 80 to about 15
0 m ² / g. ) The substance is fine and / or
Alternatively, it is often a substance having a porous structure. The basicity of the basic inorganic compound having a specific volume of about 3 ml / g or more,
When the inorganic compound is dissolved or suspended in distilled water at a concentration of 4% by weight, the pH becomes alkaline, preferably the pH is more than 7 and 12 or less, more preferably the pH is about 8 to 1 or less.
1, more preferably a compound having a pH of about 8-10. Examples of such basic inorganic compounds include calcium carbonate, calcium silicate, and special calcium silicate (eg, Fluorite RE [trade name, manufactured by Tokuyama Soda Co., Ltd.])
Alkaline earth metal salts such as calcium salts such as calcium oxide, calcium sulfate or calcium chloride and their corresponding magnesium salts, or alkali metal salts such as sodium salts such as sodium carbonate or sodium hydrogen carbonate. Alkaline earth metal salts, more preferably calcium salts, specifically, special calcium silicate (eg, Fluorite RE [trade name, manufactured by Tokuyama Soda Co., Ltd.]), calcium carbonate or calcium silicate, Preferably, special calcium silicate (eg, Florite RE [trade name, manufactured by Tokuyama Soda Co., Ltd.]) and the like are exemplified.
These can be used alone or in combination. By blending a basic inorganic compound having such a specific specific volume, a decrease in the content of tocopherol succinate or a salt thereof is suppressed, and a highly stable vitamin preparation can be obtained.

The content of tocopherol succinate or a salt thereof 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. is there. The content of the vitamin B ₁ or a salt thereof in the vitamin preparation of the present invention is about 0.5%.
01-85% by weight, preferably about 0.1-50% by weight,
More preferably, it is about 0.5 to 40% by weight. In the vitamin preparation of the present invention, the amount of tocopherol succinate or a salt thereof incorporated in one preparation is, for example, about 1 to 30.
0 mg, preferably about 2-100 m, for example.
g. Further, in the vitamin formulation of the present invention, the amount of vitamin B ₁ class or a salt thereof is formulated in one formulation, for example, in the range of about 0.1 to 300,
Preferably about 1 to 200 mg, more preferably about 1 to 1 mg
The range is 00 mg. In vitamin preparations of the present invention, the mixing ratio of the vitamin B ₁ class or its salt to the tocopherol succinate or a salt thereof, about 0.001 relative tocopherol succinic acid or a salt thereof 1 part by weight
100 parts by weight, preferably about 0.01 to 50 parts by weight, more preferably about 0.1 to 10 parts by weight. In the vitamin preparation of the present invention, the blending amount of the basic inorganic compound having a specific volume of about 3 ml / g or more to tocopherol succinate or a salt thereof is 10 tocopherol succinate or a salt thereof.
0 parts by weight, for example, about 10 parts by weight or more, specifically about 10 to 150 parts by weight, preferably about 10 to 120 parts by weight.
Parts by weight.

[0009] The particle was blended tocopherol succinate or a salt thereof for use in the formulation described below, and vitamin B ₁ class or granules formulated with a salt thereof is the specific volume of about 3 ml / g or more It may be coated with a coating agent in either a state containing or not containing a basic inorganic compound. Examples of the coating agent include hydroxypropylcellulose, hydroxypropylmethylcellulose
(Eg, TC-5 [trade name, manufactured by Shin-Etsu Chemical Co., Ltd.]) or a water-soluble cellulose such as methylcellulose; a coating agent that is soluble only in an acidic region such as polyvinyl acetal diethylaminoacetate; hydroxypropyl methylcellulose phthalate; Enteric bases such as propylmethylcellulose acetate succinate or acrylic copolymer; water-insoluble bases such as ethylcellulose; further gelatin; shellac; sodium alginate; waxes; fatty acids (eg, stearic acid or palmitic acid) And its salts (eg, salts with sodium or potassium); fatty alcohols (eg, stearin alcohol or cetyl alcohol); fatty acids such as fatty acid glycerin esters and their hardened oils (eg, hardened cottonseed oil, hardened castor oil or hardened oil) Soybean oil); poly Glycerin fatty acid ester
(Eg, penta (tetra) glyceride stearate, mono (tetra) glyceride stearate or hexa (tetra) glyceride behenate); starches (eg, corn starch, potato starch, rice starch, etc.)
Glue solution obtained by heating and solidifying; talc (including sterilized talc); precipitated calcium carbonate and the like. Further, the coating agent includes:
Coating aids (e.g., polyethylene glycol (e.g., polyethylene glycol 6000 etc.) etc.), bulking agents (e.g., lactose, sugars such as granulose, starches etc.), coloring agents (e.g., tar dyes,
(Caramel, bengalara, titanium oxide, riboflavin, etc.),
Flavoring agents (eg, sweeteners, flavors, etc.) may be added as appropriate.

[0010] Further, it is an ingredient (active ingredient) used in the production of various pharmaceuticals, quasi-drugs, foods and the like, and includes tocopherol succinate or a salt thereof and vitamin B ₁
Ingredients other than a class or a salt thereof may be added during the production of the preparation of the present invention. Examples of such ingredients, such as vitamin B ₂ and its derivatives or salts thereof, vitamins of B ₆ and derivatives thereof, or salts thereof, vitamin C and its derivatives or salts thereof, vitamin D and its derivatives or salts thereof, vitamin B ₁₂ and its derivatives, or vitamins such as their salts, compositions etc. additionally containing these vitamins. Specifically, for example, the Pharmaceutical Manufacturing Guidelines ('91, Pharmaceutical Times, 579-5
96) etc., retinol acetate, retinol palmitate, vitamin A oil, liver oil, strong liver oil, ergocalciferol, cholecalciferol, d-α acetate
-Tocopherol, dl-α-tocopherol acetate, d
-Α-tocopherol, dl-α-tocopherol, flavin adenine dinucleotide sodium, folic acid, riboflavin, riboflavin sodium phosphate, riboflavin butyrate, pyridoxine hydrochloride, pyridoxal phosphate, hydroxocobalamin hydrochloride, hydroxocobalamin acetate,
Cyanocobalamin, hydroxocobalamin, mecobalamin (methylcobalamin), nicotinic acid, nicotinamide, panthenol, calcium pantothenate, sodium pantothenate, biotin, potassium aspartate
Magnesium equivalent mixture, inositol hexanicotinate, ursodesoxycholic acid, L-cysteine hydrochloride, L-cysteine, orotic acid, γ-oryzanol,
In addition to calcium glycerophosphate, calcium gluconate, calcium lactate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, glucuronolactone, glucuronamide, sodium chondroitin sulfate, processed garlic, carrots, yoquinin, etc. Caffeine used, anhydrous caffeine, vitamins such as carnitine chloride, minerals (e.g., magnesium, calcium, iron, etc.), herbal medicines (e.g., roxio powder, carrot extract, gouow, etc.), antacids (e.g., , Synthetic hydrotalcite, etc.) may be included in the formulations of the present invention. One or more of these components can be appropriately added in an appropriate amount or an appropriate mixing ratio within a range that does not hinder the present invention.

For example, in the vitamin preparation of the present invention, for example, vitamin B ₆ and its derivatives or salts thereof (eg,
Pyridoxine hydrochloride, pyridoxal phosphate, etc.)
A preparation may be contained at 1 to 80% by weight, preferably about 0.2 to 50% by weight. Similarly, in the vitamin preparation of the present invention, for example, vitamin B ₁₂ and its derivative or a salt thereof (e.g., hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, hydroxocobalamin, mecobalamin (methylcobalamin), etc.) in an amount of about 0.00001 to 20% by weight, preferably about 0.000
1 to 10% by weight, more preferably about 0.0005 to 2% by weight, γ-oryzanol about 0.1 to 30% by weight, preferably about 0.2 to 20% by weight, and folic acid to about 0.005 to 1%.
0% by weight, preferably about 0.005 to 5% by weight, more preferably about 0.01 to 3% by weight.
In vitamin preparations of the present invention, the combination of active ingredients, such as tocopherol succinic acid or a salt thereof and vitamin B ₁ class or a salt thereof (preferably activated vitamin B ₁ derivative or a salt thereof with an S-S bond), further Vitamin B ₆ and its derivatives or their salts (preferably pyridoxine hydrochloride, pyridoxal phosphate) and vitamin B ₁₂ and its derivatives or their salts (preferably mecobalamin or hydroxocobalamin), preferably all of the above components Are preferred. These active ingredients preferably contain about 1 to 40% by weight of tocopherol succinate or a salt thereof and vitamin B _{1 based on the} whole preparation.
S or a salt thereof (preferably activated vitamin B ₁ derivative or a salt thereof with an S-S bond) about 1 to 40% by weight,
Vitamin B ₆ and its derivatives or their salts
(Preferably pyridoxine hydrochloride, pyridoxal phosphate)
About 0.2 to 50 wt%, and vitamin B ₁₂ and its derivatives or their salts (preferably mecobalamin or hydroxocobalamin) about 0.0005 wt%
Is blended.

When the preparation of the present invention is produced, additives generally used in the preparation, for example, excipients (eg, lactose, starches such as corn starch, etc.) are used in an amount not to impair the effects of the present invention. Crystalline cellulose, granulose, porous substance, etc., light silicic anhydride), binder (eg, pregelatinized starch, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, pullulan, gum arabic powder, etc.), disintegrant (eg, carboxy Methylcellulose calcium, croscarmellose sodium, crospovidone, low-substituted hydroxypropylcellulose, partially pregelatinized starch, etc., lubricants (eg, magnesium stearate, calcium stearate, etc.), coloring agents (eg, tar dye, caramel, Bengala, titanium oxide,
Riboflavins, etc.), flavoring agents (eg, sweeteners, flavors, etc.), coating agents selected from the above coating agents and coating aids (preferably, hydroxypropyl methylcellulose (eg, TC-5 [trade name, Shin-Etsu Chemical Co., Ltd. Company-made] etc.),
Polyethylene glycol (e.g., polyethylene glycol 6
000), talc (including sterile talc), precipitated calcium carbonate) and the like may be incorporated or coated in the preparation.

[0013] Production of vitamin preparations of the present invention, for example, tocopherol succinate or a salt thereof, blended with vitamin B ₁ class or basic inorganic compound specific volume is about 3 ml / g or more salts thereof, a method known per se Can be produced by mixing. The tocopherol succinate or a salt thereof and the vitamin B ₁ or a salt thereof at the time of the compounding are preferably in a powder form. If necessary, they may be kneaded and / or granulated to give granules, or the obtained granules may be compression-molded to give tablets. Preferably the particle volume is blended with basic inorganic compound and tocopherol succinate or a salt thereof is about 3 ml / g or more specific, by mixing the grains containing a combination of vitamin B ₁ class, compression molded tablets and the like. Granulation for obtaining the granules, for example, a rolling granulator, a stirring granulator, a fluidized granulator, a centrifugal rolling granulator, a centrifugal rolling fluidized granulator, a rolling fluidized granulator,
It can be carried out using a general pharmaceutical equipment such as an extrusion granulator. For kneading or spraying at the time of granulation, an appropriate solvent (for example, water, ethanol, acetone or a mixture thereof) can be used. Tablets obtained by compression molding, if desired, underlay treatment,
You may apply kneading spraying, kneading, syrup, etc.

The vitamin preparation of the present invention can be obtained, for example, by the following production method. Tocopherol succinate or a salt thereof, γ-oryzanol, vitamin B
₆ and its derivative or a salt thereof (eg, pyridoxine hydrochloride, etc.), a basic inorganic compound having a specific volume of about 3 ml / g or more, an excipient, and a disintegrating agent, and mixing in a dry or wet state. and grain, further optionally coated by adding a coating agent after granulation or granulation, separately granulated were mixed in a dry state or a wet state by adding vitamin B ₁ class or a salt thereof, an excipient, If desired, the powdered mecobalamin is coated at the time of granulation or after granulation with a coating agent in which folic acid is dispersed, sized to a mean particle diameter of about 300 to 500 μm, mixed with an excipient such as corn starch, and pulverized. The vitamin preparation of the present invention can be obtained by mixing with a form, disintegrant, disintegrant and lubricant and tableting. Further, if desired, a coating solution containing hydroxypropyl methylcellulose or / and polyethylene glycol or the like, and then a kneading solution comprising a coating agent containing precipitated calcium carbonate, etc., a binder and a colorant, and a coating agent and a binder And the like, and then kneading is applied, kneaded, and then syrup is applied to give a sugar-coated tablet. For the preparation of mecobalamin, for stabilization, a powder obtained by directly mixing and pulverizing mecobalamin or an excipient such as corn starch without granulation or suspension as described above is substantially free of water. It is preferable to use it in a state. Thereby, it can be incorporated into the preparation while minimizing the degradation of mecobalamin. Such a method can be generally used for any mecobalamin-containing solid preparation such as a mecobalamin single preparation other than the preparation of the present invention.

The vitamin preparation of the present invention is not limited to the above-mentioned tablets, but also includes solid preparations such as powders, granules, pills, capsules, orally disintegrating preparations, etc. in accordance with conventional methods. Preferably, a tablet is used. The size of the tablet is not particularly limited, but is preferably about 3-5 mm in thickness and about 5 mm in diameter.
10 mm. These solid preparations can also be coated with sucrose or granulose. Furthermore, the preparation of the present invention may be made into dry coated tablets and laminated tablets by a conventional method, or the preparation of the present invention may be added to the components of the sugar-coated layer to form a preparation. Vitamin preparations of the present invention obtained in this manner, can also be used as a product as such, a variety of medicinal products containing tocopherol or its succinate and vitamin B ₁ class or a salt thereof, quasi-drugs, foods, etc. An appropriate amount can be added at the time of production.

[0016] Vitamin preparation of the present invention, like the conventional tocopherol succinate or vitamin formulation of a salt and vitamin B ₁ class or a salt-containing, and effective as vitamin E and vitamin B _1, human and other Can be safely used as medicines, quasi-drugs or foods for animals (eg, mammals, birds, reptiles, etc.). For example, peripheral blood circulation disorders in humans (e.g., stiff shoulders or necks, numbness in limbs, coldness, illness), menopause (e.g., stiffness in shoulders or necks, numbness in limbs, coldness, hot flashes, etc.), irregular menstruation, neuralgia, muscle pain Prevention, treatment and nutrition of joint pain, low back pain, stiff shoulders, constipation, eye strain, physical fatigue, physical weakness during and after illness, pregnancy and lactation, scurvy, Merrell-Barrow disease, capillary bleeding, etc. 0.1-300 mg, preferably 1-30 mg of tocopherol succinate or a salt thereof for replenishment
0 mg and vitamin B ₁ or a salt thereof in an amount of 0.1 to 3
00 mg, preferably 1 to 200 mg, more preferably 1 to 100 mg of the vitamin preparation of the present invention per day.
It is orally administered once or three times.

[0017]

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

[0018]

EXAMPLE 1 400 g of d-α-tocopherol succinate, basic and having a specific volume of 10 ml / g (specific surface area 120 m ² / g (BET)
Formula)) is a special calcium silicate (FLORITE RE
[Product name] Tokuyama Soda Co., Ltd.) 200 g, γ-oryzanol 40 g, low-substituted hydroxypropylcellulose 4
0 g and 22.3 g of crystalline cellulose were treated with a vertical granulator (FM-VG-10 manufactured by Powrex) using a 4% by weight aqueous solution of hydroxypropylcellulose (HPC-L) (543 m).
and 400 ml of purified water (granule E). On the other hand, fursultiamine hydrochloride 1091.6 g, pyridoxine hydrochloride 1
000 g, 111 g of light anhydrous silicic acid (Sylysia 320 [trade name, manufactured by YK KK]) and 282.6 g of crystalline cellulose were mixed with a fluidized bed granulator (FD-3 manufactured by Powrex).
Using (S), granulation was carried out with 1270 ml of a 4% by weight aqueous solution of hydroxypropylcellulose (HPC-L) in which 4 g of folic acid was dispersed (group T). Each of the obtained two types of granulated powder (Group E and Group T) was subjected to a power mill (P-3 manufactured by Showa Machinery Co., Ltd.).
After sizing to an average particle size of about 400 μm using (S),
2 g and 508 g of the T group were taken out, and 60 g of mecobalamin (20 times powdered corn starch) and light anhydrous silicic acid (Sylysia 320 [trade name, manufactured by YK KK]) 11.1
g, low-substituted hydroxypropylcellulose (L-HPC-31)
66.6 g, 65.64 g of crystalline cellulose and 6.66 g of magnesium stearate were mixed with a rotary tableting machine (Kikusui Seisakusho, Collect 19K) to a diameter of 8 mm (6.5).
R) to produce uncoated tablets having a thickness of 4.42 mm. Next, a kneading solution 4 in which sterilized talc, precipitated calcium carbonate, granulose, gum arabic, and titanium oxide are dissolved or dispersed in purified water.
Using 17.6 g and 376 g of a dispersing agent composed of sterilized talc and gum arabic powder, kneading and spraying were performed using 369.6 g of the above-mentioned kneading solution, and sugar-coated bread (Kikusui Seisakusho) A 10-inch pan) was sugar-coated using 196 g of a syrup solution containing granulose and riboflavin to give sugar-coated tablets. The components and amounts of the three sugar-coated tablets are shown in Example 1 in Table 1.

Example 2 A sugar-coated tablet was obtained in the same manner as in Example 1 using the ingredients shown in Example 2 in Table 1. [Table 1]
The compounding components and the compounding ratios shown in the column of Example 2 are values per three sugar-coated tablets.

Example 3 A sugar-coated tablet was obtained in the same manner as in Example 1 by using the ingredients shown in Example 3 in Table 1. [Table 1]
The compounding components and the compounding ratios shown in the column of Example 3 are values per three sugar-coated tablets. The specific volume of calcium carbonate is 4 ml / g.

Example 4 A sugar-coated tablet is obtained in the same manner as in Example 1 using the ingredients shown in the column of Example 4 in Table 1. [Table 1]
The compounding components and the compounding ratios shown in the column of Example 4 are values per three sugar-coated tablets. Example 5 Dragees are obtained in the same manner as in Example 1, using the components shown in Example 5 in Table 1. [Table 1]
The compounding components and compounding ratios shown in the column of Example 5 are values per three sugar-coated tablets.

[Table 1] * Mecobalamin mixed and crushed powder: Mecobalamin 1.5 mg, thyricia 0.9 mg, corn starch 27 mg and microcrystalline cellulose 0.6 mg mixed 20 times powder

Comparative Example 1 A sugar-coated tablet was obtained in the same manner as in Example 1 except that the ingredients shown in Comparative Example 1 in Table 2 were used. The most significant difference between Comparative Example 1 and Example 1 is that, in place of the special calcium silicate (Fluorite RE (trade name, manufactured by Tokuyama Soda Co., Ltd.)) in Group E of Example 1, it is neutral and Specific volume is 7ml / g
(Silicia 320 [trade name, manufactured by YK FF Co., Ltd.]) having a specific surface area of 300 m ² / g (BET formula). In addition, the compounding components and compounding ratios shown in Comparative Example 1 in Table 2 are values per three sugar-coated tablets.

Comparative Example 2 A sugar-coated tablet was obtained in the same manner as in Example 1 by using the ingredients shown in Comparative Example 2 in Table 2. The most significant difference between Comparative Example 2 and Example 1 is that, instead of the special calcium silicate (Fluorite RE (trade name, manufactured by Tokuyama Soda Co., Ltd.)) in Group E of Example 1, the basic difference was obtained. One example is the use of magnesium metasilicate aluminate (Neusilin [trade name, manufactured by Fuji Chemical Co., Ltd.]) having a volume of 2.5 ml / g. In addition, the compounding ingredients and compounding ratios shown in Comparative Example 2 in Table 2 are values per three sugar-coated tablets.

[Table 2]

EXPERIMENTAL EXAMPLE 1 The sugar-coated tablets obtained in Example 1, Example 2, Example 3, Comparative Example 1 and Comparative Example 2 were stored in a glass bottle at 40 ° C. for 4 weeks. The content of d-α-tocopherol succinate was measured by liquid chromatography. Table 3 shows the results of calculating the residual ratio of the sugar-coated tablet before the 4-week storage test (initial) from the content obtained by the measurement. In the vitamin preparations of the present invention represented by Examples 1, 2 and 3, no decrease in the content of d-α-tocopherol succinate was observed, but the control represented by Comparative Examples 1 and 2 In the vitamin preparations of the group, a decrease in the content of d-α-tocopherol succinate was confirmed. From these results, it was found that excellent stability can be obtained by adding a basic inorganic compound having a specific volume of about 3 ml / g or more to d-α-tocopherol succinate.

[Table 3]

[0025]

EFFECT OF THE INVENTION The vitamin preparation of the present invention is stable and suppresses a decrease in the content of tocopherol succinate or a salt thereof,
Very little change in quality over time.

Claims (6)

[Claims] 1. A tocopherol succinate or vitamin preparations by blending a salt thereof, vitamin B ₁ class or basic inorganic compound salt thereof and specific volume is about 3 ml / g or more. 2. The vitamin preparation according to claim ₁ , wherein the vitamin B ₁ or a salt thereof is an active vitamin B ₁ derivative or a salt thereof. 3. Tocopherol succinate or a salt thereof
The vitamin preparation according to claim 1, wherein a basic inorganic compound having a specific volume of about 3 ml / g or more is blended in an amount of 10 parts by weight or more based on 0 part by weight. 4. Tocopherol succinate or a salt thereof is d.
The vitamin preparation according to claim 1, which is a body. 5. tocopherol succinate or characterized in that it contains a grain of salt thereof and specific volume are formulated with a basic inorganic compound is about 3 ml / g or more, and a particle containing a combination of vitamin B ₁ class or a salt thereof And vitamin preparations. 6. A tocopherol succinate or a salt thereof and a preparation containing vitamin B ₁ or a salt thereof, wherein a basic inorganic compound having a specific volume of about 3 ml / g or more is blended. How to stabilize the salt.