JP3505734B2 - Formulation for oral administration containing sodium ecabet - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a pharmaceutical preparation for oral administration containing ecabet sodium.

[0002]

BACKGROUND OF THE INVENTION Ecabet sodium (monosodium sulfodehydroabietate) [Chemical name: 1,4a-dimethyl-1-carboxy-6-sulfo-7-isopropyl-1,2,3,4,4a, 9, [10,10a-octahydrophenanthrene monosodium] is an excellent drug as a therapeutic agent for gastric ulcer and the like, showing an excellent gastric mucosal protective action when orally administered, but it is also a drug having a bitter and bitter taste.

Film coating is effective in the case of tablets in order to taste-eliminate a pharmaceutical preparation containing such a peculiar-tasting drug, but in the case of granules, fine granules and powders, it has a large surface area and thus film coating is possible. It is difficult to mask the taste by [Pharma Tech Japan, Vol. 6, 841-8]
50 (1990)].

In addition, a so-called flavoring / flavoring agent is blended,
A sensory method for masking the taste and smell of a drug is also known, but in the case of ecabet sodium, it was difficult to sufficiently mask the bitterness by simply adding a commonly used sweetener or umami component. .

[0005]

DISCLOSURE OF THE INVENTION The present invention is intended to provide a preparation for oral administration containing ecabet sodium which masks bitterness and is excellent in ingestion feeling.

[0006]

The present invention comprises a coating preparation having a coating film layer on the surface of a core substance containing ecabet sodium and 1-menthol, or the surface of the core substance. A sodium eglutinate-containing preparation for oral administration, comprising a coating film layer containing sodium glutamate.

The formulation of the present invention comprises preparing a core substance containing ecabet sodium, which is a pharmaceutically active ingredient, and subjecting the core substance to film coating with a film-forming component, and then externally adding 1-menthol, or It can be produced by applying a film coating containing sodium glutamate to the core substance.

In the preparation of the present invention, it is preferable to use, as the core substance containing ecabet sodium (hereinafter, abbreviated as the core substance containing the main drug), granules, fine granules or the like granulated. Average particle size is about 50-3000
It is preferable to use granules having a spherical shape or a cylindrical shape having a particle size of μm, especially about 100 to 1700 μm.

Examples of such a core substance containing a main drug include granules prepared by appropriately mixing ecabet sodium with an excipient, a disintegrating agent, and / or a binder, and using an inert carrier particle as a central core. It is also possible to use the one coated with ecabet sodium on the nucleus.

Any of the excipients, disintegrants, and / or binders used in the preparation of the above-mentioned active substance-containing core substance can be used, as long as they are commonly used in this technical field.

For example, the excipients include lactose, sucrose, mannitol, sorbitol, glucose, starch, crystalline cellulose and the like, and the disintegrants include starch, carboxymethylcellulose, carboxymethylcellulose calcium, low-substituted hydroxypropylcellulose. , Partially pregelatinized starch and the like, and examples of the binder include starch, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, dextrin, ethylcellulose and the like. All of these are not particularly limited as long as they are commonly used in preparations for oral administration.

Further, as the inert carrier particles, for example,
Sucrose, lactose crystals, or those produced from sucrose, starch, lactose, crystalline cellulose and the like can be preferably used, and those having an average particle size of about 100 to 1000 μm are preferable.

For example, when the granules prepared by mixing ecabet sodium with an excipient, a disintegrating agent, and / or a binder are used as the active substance-containing core substance, the preparation is carried out by a conventional method in this technical field. That is, it can be carried out by a wet extrusion granulation method, a rolling granulation method, a fluidized bed granulation method, a dry granulation method or the like. For example, in the case of the wet granulation method, ecabet sodium is mixed with an appropriate excipient, a disintegrating agent, etc., and the mixture is kneaded with a binder solution, and then granulated using a commercially available granulating apparatus and dried. It can be implemented by At this time, water can be preferably used as the solvent used for the kneading.

Further, for example, when the active substance-containing core substance having an inert carrier particle as a central core and coated with ecabet sodium is used, the preparation is carried out, for example, by using a binder in an appropriate solvent (water, lower solvent). While spraying a solution dissolved in alcohol, or a mixture thereof) on the inert carrier particles, add ecabet sodium or a mixture thereof with an excipient, a disintegrating agent, a lubricant and the like little by little. It can be carried out by a conventional method such as a tumbling granulation method, a pan coating method, a fluidized bed coating method and the like.

In the preparation of the present invention, as film-forming components used for film coating of the core substance containing the active ingredient, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl acetal dimethylaminoacetate, aminoalkyl methacrylate copolymer E, methacrylic acid copolymer, amino Alkyl methacrylate copolymer RS, carboxymethylethyl cellulose, polyvinyl alcohol, vinyl acetate resin, wax, or a combination of two or more thereof can be preferably used, and hydroxypropylmethyl cellulose and hydroxypropyl cellulose are particularly preferable. Further, the film-forming component may be used in combination with a coating aid, and examples of such a coating aid include fluidizing agents such as hydrous silicon dioxide, silicic acid anhydride, stearic acid, calcium stearate, magnesium stearate, and talc. , Macrogol, glycerin, titanium oxide and the like.

Film coating of the active substance-containing core substance can be carried out by a conventional coating method such as a fluidized bed coating method or a pan coating method. For example, a film-forming component (in the case of a film-coated preparation containing sodium glutamate, sodium glutamate is added thereto) and, if necessary, a suitable coating aid, a suitable solvent such as water, Dissolve or disperse in ethanol, isopropyl alcohol, or a mixture thereof, and spray-coat this coating solution on the core substance containing the main drug using a commercially available fluidized bed apparatus, coating pan, centrifugal tumbling fluidized bed apparatus, etc. It is possible to easily obtain a coating preparation. The coating rate [(weight of coating film layer / weight of core compound-containing core substance) × 100] is
It varies depending on the content and type of ecabet sodium, excipient, disintegrant, binder, etc. contained in the main drug-containing core substance, but is usually about 1-40%, more preferably about 5-15%.
It is desirable to set the degree.

When a film-coated preparation containing sodium glutamate is prepared, for example, the film coating is carried out as described above using a coating liquid containing sodium glutamate together with the above-mentioned film-forming components and the like. According to the above, the preparation of the present invention can be obtained. The sodium glutamate used in the preparation of the invention is not particularly limited as long as it is one that is usually used in preparations for oral administration.

When the preparation of the present invention contains 1-menthol, the preparation of the present invention can be obtained by externally adding 1-menthol to the coating preparation obtained as described above. You can External addition of 1-menthol can be easily carried out by mixing it alone or together with a suitable excipient and a fluidizing agent, for example, in a commercially available mixer. Moreover, 1-menthol used in the preparation of the present invention is not particularly limited as long as it is one that is usually used in preparations for oral administration.

In the thus-obtained preparation of the present invention, the amount of each component blended is such that the main drug, ecabet sodium, is about 25 to 95% by weight, especially 50 to 90% by weight in the main drug-containing core substance. It is preferable that the amount is 5 to 95% by weight, especially 10 to 90% by weight.
Further, the film-forming component is preferably blended in the preparation in an amount of about 1 to 30% by weight, particularly 2 to 10% by weight.

In the preparation of the present invention containing 1-menthol, 1-menthol is 0.001 to 1% by weight,
In particular, it is preferable that the amount is 0.03 to 0.1% by weight, and in the preparation of the present invention in which sodium glutamate is added, sodium glutamate is added in an amount of 0.
It is preferable to add 5 to 20% by weight, especially 3 to 5% by weight.

If desired, the formulation of the present invention may be externally added with a fluidizing agent. Examples of such fluidizing agents include hydrous silicon dioxide, talc, magnesium stearate,
Examples thereof include calcium stearate. Further, the preparation of the present invention may optionally have a flavoring agent such as glutamic acid, aspartic acid, inosinic acid, aspartame, glycyrrhizic acid, wax or cyclodextrin, and β
-Carotene, tar pigments, lake pigments, colorants such as caramel, iron oxide and copper chlorophyll may be contained.

If desired, the formulation of the present invention can be made into a desired dosage form by a conventional method such as sizing and tableting. Such dosage forms include tablets, granules, fine granules, powders,
Formulations for oral administration such as capsules are included.

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

[0024]

【Example】

Example 1 70 parts by weight of ecabet sodium, 5 parts by weight of D-mannitol, and 11 parts by weight of low-substituted hydroxypropyl cellulose were mixed and put into a stirring granulator (Shinagawa type mixer, Dalton), and hydroxypropyl methyl cellulose was added thereto. Dissolve 4 parts by weight in water, add, and knead for about 10 minutes. After extruding the kneaded product with an extrusion granulator having a hole diameter of 0.5 mm (rotary granulator, Kikusui Seisakusho)
Dry at 5 ° C for 5 hours. 8 parts by weight of hydroxypropyl methylcellulose, 2 parts by weight of Macrogol 6000 and 1 part by weight of talc were dissolved or dispersed in water,
Coating is performed using a fluidized bed granulation coating device (Flow Coater, Freund Sangyo). After drying the coated granules thus obtained at 40 ° C. for 10 minutes,
l-Menthol 0.03-0.1 part by weight (0 part by weight for the control example) and 0.2 part by weight of hydrous silicon dioxide were added and mixed to obtain a preparation for oral administration containing ecabet sodium. The obtained granules (1 g) were contained in the mouth, and the time required until the bitterness was stated was measured. The results are shown in Table 1.

[0025]

[Table 1]

Example 2 50 parts by weight of ecabet sodium, 32 parts by weight of lactose, and 5 parts by weight of carboxymethyl cellulose calcium were mixed,
Put in a stirring granulator (Shinagawa type mixer, Dalton), add 3 parts by weight of polyvinylpyrrolidone dissolved in water, and add
Knead for about 20 minutes. The kneaded product is extruded by an extrusion granulator (rotary granulator, Kikusui Seisakusho) having a hole diameter of 0.8 mm, and the obtained granules are dried at 45 ° C. for 5 hours. This is coated with a liquid in which 9 parts by weight of hydroxypropylmethyl cellulose and 1 part by weight of hydrous silicon dioxide are dissolved or dispersed in water using a centrifugal tumbling fluidized bed apparatus (Spiral Flow, Freund Industrial). The coated granules thus obtained are dried at 40 ° C. for 20 minutes,
l-menthol 0.03 part by weight and talc 0.2 part by weight were added and mixed to obtain a preparation for oral administration containing ecabet sodium.

Example 3 75 parts by weight of ecabet sodium and 12 parts by weight of corn starch were mixed and placed in a high-speed stirring granulator (high speed mixer, Fukae Kogyo Co., Ltd.), and 3 parts by weight of hydroxypropyl cellulose was dissolved in water. And add and knead for about 10 minutes. The kneaded product is extruded with an extrusion granulator having a hole diameter of 0.7 mm (rotary granulator, Kikusui Seisakusho), and the obtained granules are dried at 40 ° C. for 7 hours. This is a liquid (coating liquid I) in which 4 parts by weight of hydroxypropylmethylcellulose, 0.5 parts by weight of Macrogol 4000 and 0.5 parts by weight of talc are dissolved or dispersed in a fluid bed granulation coating apparatus (flow coater). , Freund Industries). Next, a coating liquid II was prepared by adding 3 to 5 parts by weight of sodium glutamate (0 parts by weight for the control example) to the coating liquid I,
Further coating is performed using a fluidized bed granulation coating apparatus (Flow Coater, Freund Sangyo). The coated granules thus obtained were dried at 40 ° C for 10 minutes to obtain a preparation for oral administration containing ecabet sodium. 1 g of the thus obtained granules was contained in the mouth, and the time required for the development of bitterness was measured. The results are shown in Table 2.

[0028]

[Table 2]

Example 4 30 parts by weight of spherical sucrose (non-pareil, Freund industry) was placed in a centrifugal fluidized coating granulator (CF granulator, Freund industry), and 4 parts by weight of hydroxypropylmethyl cellulose was dissolved in water. While spraying the solution, a mixed powder of 40 parts by weight of ecabet sodium and 16 parts by weight of talc is dispersed and granulated. It is dried in the same apparatus at 45 ° C. for 30 minutes. Hydroxypropylmethylcellulose (4 parts by weight), glycerin (0.5 parts by weight), sodium glutamate (4 parts by weight) and talc (1.5 parts by weight) are dissolved or suspended in water, and coating is continuously performed using this solution. The coated granules thus obtained were dried in the same apparatus at 45 ° C. for 30 minutes to obtain a preparation for oral administration containing ecabet sodium.

[0030]

[Effects of the Invention] l-menthol is blended in a coating preparation having a coating film layer provided on the surface of a core substance containing ecabet sodium, or a coating film layer containing sodium glutamate is provided on the surface of the core substance. As a result, the bitterness of ecabet sodium is masked, and a pharmaceutical preparation for oral administration that is excellent in ingestion feeling can be obtained.

Front page continuation (72) Inventor Koji Matsubara 3-4-6 Dainichi-dori, Chuo-ku, Kobe-shi, Hyogo (56) References JP-A-4-193823 (JP, A) JP-A-4-312523 (JP , A) Yutaka ITO et al. J. Pharmacobio-Dyn. , September 14, 1991, 14 (9), p. 547-554 (58) Fields investigated (Int.Cl. ⁷ , DB name) A61K 31/19-31/80 A61K 9/00-9/72 A61K 47/00-47/48 A61P 1/04 PubMed

Claims (3)

(57) [Claims] 1. A coating preparation comprising a coating film layer provided on the surface of a core substance containing ecabet sodium and 1-menthol, or a coating film layer containing sodium glutamate provided on the surface of the core substance. A preparation for oral administration, which comprises: 2. The preparation for oral administration according to claim 1, which comprises a coating preparation in which a coating film layer is provided on the surface of a core substance containing ecabet sodium and 1-menthol. 3. The preparation for oral administration according to claim 1, wherein a sodium glutamate-containing coating film layer is provided on the surface of a core substance containing ecabet sodium.