JP3125221B2 - Sofalcone-containing solid preparation - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a solid preparation containing sofacolcon.

2. Prior Art and Problems to be Solved by the Invention Sofalcone is used as a remedy for gastritis and gastric ulcer. However, when Sofalcon was formulated in a usual manner, it could not be said to have good bioabsorbability.

An object of the present invention is to provide a preparation having an improved in vivo absorbability of sofalcone.

Means for Solving the Problems The present invention is a solid preparation containing sofalcone, a water-soluble excipient, an antacid and a nonionic surfactant.

The particle size of the sofalcone used in the present invention is 10 μm
Hereinafter, it is preferably 2-3 μm.

In addition, lactose, mannitol, starch (eg, corn starch, potato starch, etc.), sucrose, glucose, and the like can be used as the water-soluble excipient, and two or more of these may be used in combination. The amount of the water-soluble excipient is 10 to 90% by weight, preferably 50 to 60% by weight, based on the total amount of the preparation.

As the antacid, sodium hydrogen carbonate, calcium hydrogen phosphate, sodium metasilicate aluminate, Alkamac and the like can be used, and two or more of these may be used in combination. The amount of the antacid is less than or equal to the amount that the antacid can be used as an excipient.
0.5 to 1 part per part.

As the nonionic surfactant, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester and the like can be used, and two or more of these may be used in combination. The compounding amount of the nonionic surfactant is in the range of 0.01 to 0.5 part, preferably 0.1 to 0.2 part based on 1 part of sofalcone.

The solid preparation of the present invention can be produced, for example, as follows.

That is, a water-soluble excipient and an antacid are added to and mixed with sofacalcon, and the mixture is granulated by a normal granulation method using a solution in which a nonionic surfactant and a binder are dissolved in a solvent. It can be manufactured by preparing various solid preparations by the method.

Here, as the binder, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone and the like can be used. Further, as the solvent, purified water, ethanol or a mixture thereof can be used.

After granulation, tablets or capsules are prepared using a disintegrant and / or a lubricant, and examples of the disintegrant include low-substituted hydroxypropylcellulose, calcium carboxymethylcellulose, and Acdizol. Also, as a lubricant calcium stearate,
Magnesium stearate, talc, hardened oil and the like can be used.

Examples Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples.

Example 1 50 g of sodium bicarbonate and 1 sucrose in 100 g of sofarcone
After adding and mixing 50 g, mannitol 200 g, and corn starch 470 g, a solution prepared by dissolving 20 g of hydroxypropylcellulose and 10 g of polysorbate 80 in 250 g of a mixed solution of purified water: ethanol = 1: 2 was added, and mixed by tumbling granulation.

This was granulated by an extrusion granulator using a screen having a diameter of 0.5 mm, and then dried by a fluidized bed granulator to obtain a granule.

Example 2 100 g of Sofalcone, 100 g of calcium hydrogen phosphate, lactose
After adding and mixing 200 g, 330 g of corn starch and 230 g of glucose, 30 g of hydroxypropylcellulose and 10 g of polysorbero 80 dissolved in 800 g of purified water were used as a binder, granulated with a fluidized bed granulator and dried to obtain a fine granule. Was.

Example 3 100 g of Sofalcone, 100 g of calcium hydrogen phosphate, 195 g of mannitol, 100 g of potato starch and 25 g of calcium carboxymethylcellulose were added and mixed, followed by 30 g of hydroxypropylmethylcellulose and 80 g of polysorbate 80.
A solution prepared by dissolving 20 g in 800 g of purified water was used as a binder, granulated by a fluidized bed granulator, dried, and then sieved using a No. 22 sieve. Add 15g of calcium stearate and 15g of talc to this
A tablet weighing 300 mg was obtained.

Example 4 50 g of sodium bicarbonate, 240 g of mannitol, 100 g of lactose and 30 g of low-substituted hydroxypropylcellulose were added to 100 g of sofalcone and mixed, and then 25 g of hydroxypropylmethylcellulose and 20 g of polysorbate 80 were mixed in purified water: ethanol = 1: 2. The solution dissolved in 800 g was used as a binder, granulated with a fluidized bed granulator, dried, and then sieved using a No. 30 sieve. To this, 15 g of calcium stearate and 20 g of hardened oil were added, and 300 mg was filled in a No. 1 capsule to obtain a capsule.

Comparative Example 1 100 g of sofacalcon, 100 g of calcium hydrogen phosphate, 300 g of low-substituted hydroxypropylcellulose, and 460 g of microcrystalline cellulose were added and mixed, and then 30 g of hydroxypropylcellulose and 10 g of polysorbate 80 dissolved in 1000 g of purified water were used as a binder. The mixture was granulated with a fluid bed granulator and dried to obtain a fine granule.

Comparative Example 2 lactose 250g, corn starch 380g,
After adding and mixing 230 g of glucose, 30 g of hydroxypropylcellulose and 10 g of polysorbate 80 dissolved in 800 g of purified water were used as a binder, and the mixture was granulated with a fluid bed granulator and dried to obtain fine granules.

Comparative Example 3 100 g of Sofalcone, 100 g of calcium hydrogen phosphate, lactose
After 200 g, 340 g of corn starch and 230 g of glucose were added and mixed, 30 g of hydroxypropylcellulose dissolved in 800 g of purified water was used as a binder, and the mixture was granulated with a fluid bed granulator and dried to obtain fine granules.

Test Example (Absorptivity Test of Sofalcone-Containing Preparation) In vivo absorption tests of the preparations of Examples 2, 3 and Control Examples 1 to 3 were performed in humans. Example 2 is a fine granule, and as an example in which the particles are finest and have good absorption, Example 3 is a tablet,
As an example where it is expected that absorption is poor due to compression and high content of sofalcone, Control Example 1 is an example containing no water-soluble excipient and Control Example 2 is an example containing no antacid. Comparative Example 3 was a sample as an example containing no nonionic surfactant.

The test was performed with 5 subjects in each group and 25 subjects in total, and the dose of the sample was
100 mg. After the administration of each sample, 10 ml of the blood was collected from the forearm skin vein of the subject once at a predetermined time after the administration of each sample. This blood is analyzed by liquid chromatography,
Sofalcon concentration in plasma was measured. The result is
Shown in the figure.

FIG. 1 shows that the preparations of the present invention were used in Examples 2 and 3
Preparations had good bioabsorbability, whereas Control Examples 1 to
Formulation 3 had poor bioabsorbability.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a diagram showing the amount of absorption of sofalcone, the vertical axis represents the concentration of sofalcone in plasma, and the horizontal axis represents time. In addition,
The area at the bottom of the graph is the absorption amount of sofalcone.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI A61P 1/04 A61P 1/04 (72) Inventor Shigeru Itai 3-24-1, Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. 56) References JP-A-54-32634 (JP, A) JP-A-57-146722 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 31/192, 33/00 A61K 47 / 26,47 / 34

Claims (1)

(57) [Claims] 1. An oral solid preparation for the treatment of gastritis and gastric ulcer, which comprises sofacolcon, a water-soluble excipient, calcium hydrogen phosphate and polysorbate 80.