JP2003012515A - Tocopherol preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a tocopherol preparation free from tabletting failures and a tocopherol preparation without tabletting failures. SOLUTION: This tocopherol preparation includes the tocopherol, Croscarmellose sodium and hydroxypropyl cellulose of low degree of substitution.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a tocopherol preparation which does not cause tableting trouble. The invention also relates to the resulting tableting-free tocopherol formulations.

[0002]

BACKGROUND OF THE INVENTION Tocopherol is a peripheral circulatory disorder such as prevention and treatment of vitamin E deficiency, intermittent claudication, arteriosclerosis, venous thrombosis, thrombophlebitis, diabetic retinopathy, frostbite and cold extremity. It is effective in alleviating various symptoms such as prevention of increase in lipid peroxide and is widely used in medicines and foods. Generally, when manufacturing a tocopherol preparation, due to the low melting point of tocopherol and the melting point drop due to mixing with other components, heat generated during tableting causes sticking (sticking) which is one of the tableting obstacles. Occurs. As a method for preventing tableting troubles such as sticking with a punch, it is conceivable to reduce the amount of tocopherol in the preparation or increase the amount of lubricant such as magnesium stearate or talc. However, reducing the amount of tocopherol results in multiple tablets in a single dose, and increasing the amount of lubricant causes other tableting problems such as capping phenomenon and tablet hardness reduction during production, which is not preferable.

From the above point of view, a method for producing a tocopherol preparation which does not cause tableting trouble and a tocopherol preparation which does not have tableting trouble have not been obtained yet.

[0004]

SUMMARY OF THE INVENTION The present invention has been made from the above viewpoint, and it is an object of the present invention to provide a method for producing a tocopherol preparation which does not cause tableting disorders and a tocopherol formulation which does not have tableting disorders.

[0005]

Means for Solving the Problems As a result of intensive studies in view of the above points, the present inventors have found that by mixing croscarmellose sodium and low-substituted hydroxypropylcellulose in tocopherol, it is The inventors have found that the tableting disorder of No. 1 is improved and completed the present invention.

That is, the present invention is as follows. (1) A tocopherol preparation containing tocopherol, croscarmellose sodium, and low-substituted hydroxypropylcellulose. (2) A method for producing a tocopherol preparation, which comprises mixing croscarmellose sodium and low-substituted hydroxypropylcellulose in tocopherol and tableting.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is described in detail below.

In the present invention, tocopherol is a concept that includes tocopherol derivatives and salts thereof in addition to tocopherol. Specifically, d-α-tocopherol, dl-α-tocopherol, d-α-tocopherol acetate, dl-α-tocopherol acetate, dl-α-nicotinic acid tocopherol, succinate dl-α-tocopherol calcium, succinic acid Examples thereof include d-α-tocopherol and dl-α-tocopherol succinate. They are,
It may be a single kind or a mixture of two or more kinds.

In the present invention, the low degree of substitution referred to as low-substituted hydroxypropyl cellulose means, for example, the case where the hydroxypropoxyl group is 5 to 16%.

The tocopherol, croscarmellose sodium and low-substituted hydroxypropylcellulose in the tocopherol preparation of the present invention are each added in an amount effective to exert the effects of the present invention, but they do not cause tableting problems during preparation of the preparation. Each blending amount can be set arbitrarily as long as the effect of the present invention of improving is produced. The more preferable specific blending amount of each component is shown below.

The amount of tocopherol in the tocopherol preparation of the present invention is 1 to 40% by weight based on the total amount of the preparation.
%, Preferably 5 to 35% by weight, particularly preferably 10 to 3
It is 0% by weight.

The content of croscarmellose sodium in the tocopherol preparation of the present invention is 3 to 25% by weight, preferably 4 to 20% by weight, particularly preferably 5 to 15% by weight, based on the total amount of the preparation.

The content of low-substituted hydroxypropylcellulose in the tocopherol preparation of the present invention is 2 to 20% by weight, preferably 3 to 15% by weight, based on the total amount of the preparation.

The tocopherol preparation of the present invention may contain a drug other than tocopherol as long as the effects of the present invention are not impaired.

Examples of agents other than tocopherol include vitamin B1s (thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester salt, etc.), vitamin B1 derivatives (disetiamine hydrochloride, fursultiamine hydrochloride, octoate). Thiamin,
Shikotiamine, bisbutyamine, bisbenchamine,
Fursultiamine, prosultiamine, benfotiamine, etc.), vitamin B2s (flavin adenine dinucleotide sodium, riboflavin, sodium riboflavin phosphate, riboflavin butyrate riboflavin, etc.), vitamins B6 (pyridoxine hydrochloride, pyridoxal phosphate, etc.), vitamins B12s (hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, hydroxocobalamin, etc.), nicotinic acids (nicotinic acid, nicotinic acid amide, etc.), pantothenic acids (panthenol, calcium pantothenate, sodium pantothenate, etc.), potassium aspartate Examples include magnesium equivalent mixtures, gamma-oryzanol, sodium chondroitin sulfate, oxoamidin, and the like. These agents can be used alone or as a mixture of two or more with respect to tocopherol.

Further, the tocopherol preparation of the present invention comprises
In addition to the above components, various optional components that are acceptable as pharmaceutical additives and that can be orally administered can be added as desired. Such additives include, for example, excipients,
Examples thereof include binders, disintegrants, coloring agents, corrigents and the like.

Examples of excipients include lactose, starches, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid, calcium hydrogen phosphate and the like.

Examples of the binder include hydroxypropylmethyl cellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, pullulan and the like.

Examples of the disintegrant include carmellose calcium, corn starch and the like.

Examples of the colorant include tar dyes and ferric sesquioxide.

Examples of corrigents include stevia, aspartame, citric acid, and flavors.

The tocopherol preparation of the present invention is manufactured using the above-mentioned raw materials, and when formulating these, a usual preparation method can be used.

The preparation of the present invention is not limited as long as it is a solid preparation, and examples thereof include tablets, chewable preparations, film-coated tablets and sugar-coated tablets.

[0024]

EXAMPLES The present invention will be specifically described below with reference to examples.

[0025]

EXAMPLE 1 100 g of calcium succinate dl-α-tocopherol, 70 g of croscarmellose sodium, 70 g of low-substituted hydroxypropyl cellulose and 750 g of crystalline cellulose were mixed with a Shinagawa mixer (Shinagawa Kogyo 5DM).
L-03-R) and mixed. Then, add 200 mL of isopropanol, knead for 5 minutes, granulate, dry, and granulate with 16 mesh and add 10 g of magnesium stearate to the tablet machine (Kikusui Seisakusho Collect 19TU.
-Compression molding was performed at a tableting pressure of 1.5 t and a rotation speed of 30 rotations / minute) to produce 200 mg tablets.

[0026]

Example 2 A tablet was produced in the same manner as in Example 1 using 200 g of dl-α-tocopherol calcium succinate and 650 g of crystalline cellulose.

[0027]

Example 3 A tablet was produced in the same manner as in Example 1 using 300 g of dl-α-tocopherol calcium succinate and 550 g of crystalline cellulose.

[0028]

Comparative Example 1 Tablets were produced in the same manner as in Example 1 except that 820 g of crystalline cellulose was used instead of low-substituted hydroxypropyl cellulose.

[0029]

Comparative Example 2 Tablets were produced in the same manner as in Example 1 except that 820 g of crystalline cellulose was used instead of croscarmellose sodium. <Evaluation of Formulation and Sticking of Examples and Comparative Examples> Regarding Examples 1 to 3 and Comparative Examples 1 and 2, the presence or absence of sticking during tableting was examined.

Table 1 shows the evaluation results of formulation and sticking. Regarding the sticking evaluation, the result that sticking did not occur 5 minutes after the start of compression molding with a tableting machine was indicated by ◯, and the result that sticking occurred was indicated by x.

[0031]

[Table 1] From this result, it was found that sticking did not occur by tableting by mixing both croscarmellose sodium and low-substituted hydroxypropylcellulose in tocopherol.

[0032]

INDUSTRIAL APPLICABILITY According to the present invention, a tocopherol preparation can be produced without causing a tableting disorder.

Continued front page    (72) Inventor Hiroyuki Kawashima             1-17-9 Suzukawa Nishimachi, Fuji City, Shizuoka Prefecture (72) Inventor Yasuo Shinoda             74 Babacho, Shizuoka City, Shizuoka Prefecture (72) Inventor Toshio Inaki             6-10-203 Nishiwakacho, Mishima City, Shizuoka Prefecture F term (reference) 4C076 AA37 BB01 CC23 DD41 EE31                       EE32                 4C086 BA09 MA01 MA05 MA35 MA52                       NA03 ZC29

Claims (2)

[Claims] 1. A tocopherol preparation containing tocopherol, croscarmellose sodium and low-substituted hydroxypropylcellulose. 2. A method for producing a tocopherol preparation, which comprises mixing croscarmellose sodium and low-substituted hydroxypropylcellulose in tocopherol and tableting.