JP2001213770A - Stabilized teprenone composition, and stabilizing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a stabilized composition of teprenone. SOLUTION: This stabilized teprenone composition contains teprenone, and glycine or contains teprenon, glycine and manitol. By the addition of glycine, the formation of decomposition product of teprenone under conservation is suppressed and further, by using manitol, the coloration change in appearance can be prevented.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition containing teprenone, which is useful as a drug for treating gastric ulcer and gastritis.

[0002]

Background of the Invention and Prior Art Teprenone is a therapeutic agent for gastric ulcer and gastritis (JP-B-63-44726, JP-B-7-10).
No. 3019), and its use as a whitening agent (JP-A-6-16532) is also known.
Teprenone is a compound having an unsaturated bond and is particularly unstable against oxidation. Therefore, a technique for stabilizing by adding an antioxidant such as vitamin E (Japanese Patent Publication No. Sho 62-
No. 9096). On the other hand, since teprenone is an oily substance at room temperature, in order to prepare a dosage form as a therapeutic agent for gastric ulcer and gastritis, teprenone is adsorbed to silicic acids, etc. It is being formulated.

[0003]

The teprenone preparation as a therapeutic agent for gastric ulcer / gastritis is stabilized by blending an antioxidant such as vitamin E, and is practically used as a capsule. However, it has been found that the amount of decomposed products of teprenone increases, although in a trace amount, during the long-term storage of the teprenone formulation due to recent advances in analytical techniques. The degree of increase in the amount of the decomposed product is not an amount that affects drug efficacy, safety, and the like, but it is needless to say that a more stable preparation is desirable. The inventors of the present invention have intensively studied to solve this problem, and have found that the problem can be solved by the following means, and have completed the present invention.

[0004]

SUMMARY OF THE INVENTION The present invention is a composition comprising teprenone and glycine. The present invention is also a method for stabilizing teprenone by adding glycine.

[0005] Teprenone is a compound having the following structural formula, and its chemical name is geranylgeranylacetone or 6,
10,14,18-tetramethyl-5,9,13,17-nonadecatetraene
2-on. Teprenone has eight geometric isomers in theory, and includes any geometric isomer in the present invention. Among them, the one practically used as a drug is 3: 2 (5E: 5Z ) (9E, 13E) -6,10,14,18-tetramethyl-
5,9,13,17-nonadecatetraen-2-one.

[0006]

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Glycine is one of α-amino acids and is an important component of various proteins in aminoacetic acid.
Glycine is important as a nutrient in foods, but is also approved for use as an additive in pharmaceuticals, and a commercially available product can be easily obtained. In the present invention, by adding glycine, it is possible to prevent a decrease in the content of teprenone and to suppress an increase in the amount of decomposition products, and this is the object of the present invention.

In the present invention, the ratio of teprenone to glycine is 0.001 to glycine per 1 part by weight of teprenone.
0.1 part by weight, preferably 0.002 to 0.04
Weight.

In the composition comprising teprenone and glycine in the present invention, it is preferable to use a sugar alcohol such as mannitol (sometimes referred to as mannitol) or erythritol as an excipient. Lactose is often used as an excipient in the manufacture of pharmaceutical preparations, but lactose has relatively high reactivity because it has an aldehyde group, and is not particularly suitable for compounding a substance having an amino group. On the other hand, sugar alcohols such as mannitol and erythritol do not change appearance even when an α-amino acid such as glycine is blended, and have a moderate sweetness, so that a preparation which can be easily taken can be obtained. In the present invention, since the sugar alcohol is used as an excipient, its use amount is not particularly limited, and the use amount can be appropriately determined according to the dosage form such as capsules, granules, tablets and the like. For example, in the case of a capsule, the usual usage amount is 5 to 50 mg per unit formulation.

One example of a method for producing a composition according to the present invention is to adsorb teprenone mixed with vitamin E to silicic acids, mix mannitol, corn starch, etc., and then gradually mix glycine dissolved in macrogol 6000. Stir and granulate. After drying the obtained granules, they are sized, mixed with talc or the like, and filled into capsules to produce capsules. Since teprenone is an oil at room temperature and glycine is a crystalline solid substance, it is preferable that glycine is in uniform contact with teprenone as much as possible.

[0011]

[Effects] The effects of the present invention will be described below with reference to test examples.

Test Example 1 The granules obtained in the same manner as in Example 1 were placed in a glass bottle, opened or sealed, and then 40 ° C. and 75%
Alternatively, the content and the amount of decomposed product when stored at 60 ° C. were measured. As a control sample, granules containing no teprenone were produced and used in the same manner as in Example 1. The content and the amount of the decomposition product were measured by high performance liquid chromatography. Table 1 shows the results.
It was shown to.

[0013]

[Table 1]

From Table 1, it can be seen that the composition according to the present invention decomposes from the control formulation containing no glycine at 75% at 40.degree. C. and 60.degree. The increase in physical quantity was suppressed, and the residual ratio of teprenone was high.

Test Example 2 As shown in Table 2, the amount of glycine added per unit formulation was 0 mg, 0.1 mg, 0.3 mg, 1.
Granules were produced in the same manner as in Example 2 except that the amount was set to 0 mg or 2.0 mg, and filled in capsules. Put this sample in a glass bottle,
The content and the amount of the decomposed product when opened or sealed and stored at 40 ° C. and 75% were measured. In addition, the appearance of the contents was visually evaluated, and the results are shown in Table 3.

[0016]

[Table 2]

[0017]

[Table 3]

From Table 3, it is apparent that the increase in the amount of decomposed products during storage is suppressed and the content of teprenone increases when the amount of glycine added is 0.1 mg (0.002 parts by weight per 1 part by weight of teprenone). It is. The composition containing lactose and glycine caused a change in appearance according to the amount of glycine, whereas the composition using mannitol instead of lactose did not change the appearance.

[0019]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto.

Example 1 Tocopherol (2.0 g) was added to teprenone (1000 g) and mixed well, and the mixture was mixed with 740 g of anhydrous silica anhydride (trade name: Sylysia 350) with stirring. Next, 198 g of mannitol and 120 g of corn starch were added, mixed and further stirred, and 200 g of Macrogol 6000 in which 20 g of glycine had been dissolved was gradually added, followed by granulation. The obtained granules are dried at 40 ° C. for 3 hours and, after sieving, further 40 g of talc
And hydrated anhydrous silicic acid (trade name: Sylysia 350) 80
g was added to obtain teprenone-containing granules.

Example 2 0.1 g of tocopherol was added to 50 g of teprenone and mixed well.
50) Mix with stirring to 37 g. Next, 10.9 g of mannitol and 6 g of corn starch were added, mixed and further stirred, and 10 g of Macrogol 6000 in which 0.1 g of glycine was dissolved was gradually added to granulate. The obtained granules were dried at 40 ° C. for 14 hours. After sizing, 2 g of talc and 4 g of hydrated anhydrous silicic acid (trade name: Sylysia 350) were added to obtain granules containing teprenone, which were filled into capsules. A capsule was obtained.

Claims (4)

[Claims] 1. A composition comprising teprenone and glycine. 2. A method for stabilizing teprenone by adding glycine. 3. Glycine 0.0 part per 1 part by weight of teprenone.
A composition comprising 0.01 to 0.1 parts by weight. 4. A composition comprising teprenone, glycine and mannitol.