Solid preparations

Abstract

To provide solid preparations with improved unpleasant taste of a magnesium salt or bisacodyl in a salt-based laxative.SOLUTION: It is found that the addition of Plantago ovata as a swellable laxative can improve the unpleasant taste and the roughness in the oral cavity. That is, the present invention relates to a solid preparation containing: (A) at least one selected from the group consisting of a magnesium salt and bisacodyl in a salt-based laxative; and (B) Plantago ovata, wherein when the component (A) is magnesium oxide, the content of the component (B) is 12 to 20 pts.mass with respect to 1 pt.mass of the magnesium oxide (A), when the component (A) is magnesium hydroxide, the content of the component (B) is 2 to 20 pts.mass with respect to 1 pt.mass of the magnesium hydroxide (A), and when the component (A) is magnesium sulfate, the content of the component (B) is 0.1 to 5 pts.mass with respect to 1 pt.mass of the magnesium sulfate (A).SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a solid preparation, and more particularly to a preparation which contains an active ingredient having an unpleasant taste and which has excellent swallowability. [Background technology]

[0002] Salt laxatives such as magnesium oxide, magnesium hydroxide, magnesium sulfate, and magnesium carbonate have the effect of suppressing water absorption in the large intestine and promoting bowel movements by absorbing water into the stool, swelling it, and softening it in the intestine, and are widely used as laxatives with few side effects. In addition, because they have an antacid effect in the pharmaceutical field, they are widely used as antacids and gastric mucosa protecting ingredients in oral medications such as gastrointestinal medicines, laxatives, and cold medicines.

[0003] Bisacodyl acts directly on the mucous membrane of the large intestine, promoting intestinal peristalsis and encouraging defecation, and is widely used, mainly by oral administration (Patent Document 1). For oral administration, in order to avoid degradation in the stomach, which reduces its effectiveness, and to avoid unnecessary irritation to the gastric mucosa, many enteric-coated tablets are used, in which the tablets are coated so that they dissolve in the intestine. In the case of enteric-coated preparations, there is a risk that bisacodyl may dissolve in the stomach, so it is recommended that patients avoid taking gastrointestinal medicines containing antacid ingredients or ingesting milk within one hour before and after taking the drug.

[0004] While these active ingredients are widely used, they have been reported to have a peculiar unpleasant taste (bitterness, saltiness, etc.) (Patent Document 2, Patent Document 3).

[0005] The unpleasant taste of an oral preparation impairs the feeling of taking the preparation and causes a decrease in compliance with medication (Patent Document 4). In particular, in the case of oral preparations in the form of powders, granules, orally disintegrating tablets, chewable tablets, plain tablets, etc., the components of the oral preparation come into frequent contact with the tongue, and therefore the deterioration of the feeling of taking the preparation due to the unpleasant taste becomes significant.

[0006] Up to now, several methods for suppressing the unpleasant taste of magnesium oxide, magnesium hydroxide, and bisacodyl have been reported. For example, as a method for suppressing the unpleasant taste of magnesium oxide and magnesium hydroxide, it has been reported that an oral composition with improved feeling of ingestion, flavor, and aftertaste was obtained by combining with stevia (Patent Document 5). In addition, Patent Document 2 reports that an oral composition with improved feeling of ingestion, flavor, and aftertaste was obtained by combining with lactate and sucralose as a method for suppressing the unpleasant taste of basic inorganic salts such as magnesium oxide, magnesium hydroxide, and magnesium carbonate. In addition, for bisacodyl, a coating method containing a specific excipient has been reported as a method for masking the unpleasant taste (Patent Document 6). However, these methods require the use of a specific sweetener or a specific excipient and require a coating process, which increases the cost of raw materials and extends the process time, and there is still room for further study. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] JP 2007-5 5 9 6 9 A [Patent Document 2] JP 2016-204353 A [Patent Document 3] JP 2015-42634 A [Patent Document 4] JP 2011-6481 A [Patent Document 5] Japanese Patent Application Publication No. 9-52827 [Patent Document 6] JP 2010-120956 A Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide a solid preparation which improves the unpleasant taste of magnesium salt or bisacodyl of saline laxatives. [Means for solving the problem]

[0009] The inventors conducted various studies to solve the above problems and surprisingly found that adding Plantago ovata, a swelling laxative, could improve the unpleasant taste and also reduce the roughness in the mouth, thereby further improving the ease of taking the medicine and thus completing the present invention.

[0010] That is, the present invention provides (1) A laxative comprising (A) at least one selected from the group consisting of magnesium salts of saline laxatives and bisacodyl, and (B) Plantago ovata; When the component (A) is magnesium oxide, the content of the component (B) is 10 to 20 parts by mass per 1 part by mass of the magnesium oxide (A), When the component (A) is magnesium hydroxide, the content of the component (B) is 2 to 20 parts by mass per 1 part by mass of the magnesium hydroxide (A), When component (A) is magnesium sulfate, the content of component (B) is 0.1 to 5 parts by mass per part by mass of magnesium sulfate (A). A solid formulation comprising: (2) (A) The solid preparation according to (1), wherein the magnesium salt of the saline laxative is at least one selected from the group consisting of magnesium oxide, magnesium hydroxide, magnesium sulfate, and magnesium carbonate. (3) The solid preparation according to (1) or (2), characterized in that when the component (A) is magnesium carbonate, the content of the component (B) is 0.1 to 10 parts by mass per part by mass of the magnesium carbonate (A). (4) (B) The solid preparation according to any one of (1) to (3), wherein the content of Plantago ovata is 10 to 95% by mass based on the total mass of the solid preparation. (5) The solid preparation according to any one of (1), (2), or (4), wherein the content of (A) magnesium oxide is 1 to 9% by mass based on the total mass of the solid preparation. (6) (A) The solid preparation according to any one of (1), (2), or (4), wherein the content of magnesium hydroxide is 5 to 40% by mass based on the total mass of the solid preparation. (7) The solid preparation according to any one of (1) to (6), further comprising an organic acid. (8) The solid preparation according to any one of (1) to (7), wherein the dosage form is an orally disintegrating tablet, a chewable tablet, a plain tablet, a granule, or a powder. (9) (B) The solid formulation according to any one of (1) to (8), wherein the Plantago ovata is a Plantago ovata seed or a Plantago ovata seed coat. It is. Effect of the Invention

[0011] According to the present invention, it is possible to provide a solid preparation which suppresses the unpleasant taste of magnesium salt or bisacodyl of a saline laxative and which is easy to take. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The magnesium salt of the saline laxative of the present invention includes magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium sulfate and the like.

[0013] The magnesium oxide used in the present invention is magnesium oxide conforming to the Japanese Pharmacopoeia or food additives, and can be produced by a known method, or a commercially available product can be used. From the viewpoint of ingestibility, the content of the magnesium oxide of the present invention is preferably 1 to 9 mass%, more preferably 5 to 9 mass%, based on the total mass of the solid preparation of the present invention.

[0014] The magnesium hydroxide in the present invention is magnesium hydroxide conforming to the Japanese Pharmacopoeia Pharmaceutical Standards or Food Additives Standards, and can be produced by known methods, or commercially available products can be used. The content of the magnesium hydroxide in the present invention is preferably 1 to 50% by mass, more preferably 5 to 40% by mass, and even more preferably 5 to 33% by mass, based on the total mass of the solid preparation of the present invention from the viewpoint of intake.

[0015] The magnesium carbonate used in the present invention is magnesium carbonate conforming to the Japanese Pharmacopoeia or food additives, and can be produced by a known method, or a commercially available product can be used. From the viewpoint of ingestibility, the content of magnesium carbonate in the present invention is preferably 10 to 90% by mass, more preferably 12 to 86% by mass, based on the total mass of the solid preparation of the present invention.

[0016] The magnesium sulfate used in the present invention is magnesium sulfate conforming to the Japanese Pharmacopoeia or food additives, and can be produced by a known method or commercially available. The content of magnesium sulfate in the present invention is preferably 10 to 90% by mass, more preferably 20 to 86% by mass, based on the total mass of the solid preparation of the present invention, from the viewpoint of ingestibility.

[0017] The bisacodyl in the present invention is bisacodyl according to the Japanese Pharmacopoeia, and can be produced by a known method or commercially available. The content of bisacodyl in the present invention is preferably 0.0001 to 1% by mass, more preferably 0.0001 to 0.85% by mass, based on the total mass of the solid preparation of the present invention from the viewpoint of intake.

[0018] The Plantago ovata of the present invention may be used in any part, including seeds, stems, leaves, and roots, but seeds containing a large amount of swelling laxative components (psyllium gum) are preferred. When seeds are used, either the whole seed or only the seed coat may be used, but seed coat or seed coat powder is more preferred. Plantago ovata physically stimulates the intestinal wall by absorbing water and swelling, and increases the amount of stool, thereby exerting a laxative effect. The daily dose of Plantago ovata of the present invention is preferably 1050 to 10500 mg, more preferably 2100 to 10500 mg. The content of Plantago ovata of the present invention is preferably 10 to 95% by mass based on the total mass of the solid preparation of the present invention from the viewpoint of exerting a laxative effect. In the present invention, when magnesium oxide and Plantago ovata are blended, the blending amount of Plantago ovata is preferably 60 to 95 mass%, more preferably 84 to 92 mass%. When magnesium hydroxide and Plantago ovata are blended, the blending amount of Plantago ovata is preferably 40 to 95 mass%, more preferably 50 to 94 mass%, and even more preferably 55 to 92 mass%. When magnesium carbonate and Plantago ovata are blended, the blending amount of Plantago ovata is preferably 5 to 85 mass%, more preferably 10 to 85 mass%. When magnesium sulfate and Plantago ovata are blended, the blending amount of Plantago ovata is preferably 5 to 85 mass%, more preferably 10 to 77 mass%. When bisacodyl is blended, the blending amount of Plantago ovata is preferably 75 to 90 mass%.

[0019] Furthermore, in the present invention, when magnesium oxide and Plantago ovata are combined, the amount of Plantago ovata combined is 10 to 20 parts by mass, more preferably 12 to 20 parts by mass, and even more preferably 12 to 17.5 parts by mass per part by mass of magnesium oxide, in order to suppress the unpleasant taste of magnesium oxide or improve roughness in the oral cavity. When magnesium hydroxide and Plantago ovata are combined in the solid formulation of the present invention, the amount of Plantago ovata to be combined is 2 to 20 parts by mass, preferably 2 to 16.7 parts by mass, and more preferably 3.3 to 16.7 parts by mass, per part by mass of magnesium hydroxide in order to suppress the unpleasant taste of magnesium hydroxide and / or improve roughness in the oral cavity. When magnesium sulfate and Plantago ovata are combined in the solid preparation of the present invention, the amount of Plantago ovata to be combined is 0.1 to 5 parts by mass, preferably 0.14 to 3.5 parts by mass, per part by mass of magnesium sulfate in order to suppress the unpleasant taste of magnesium sulfate and improve roughness in the oral cavity. When magnesium carbonate and Plantago ovata are combined in the solid preparation of the present invention, the amount of Plantago ovata to be combined is 0.1 to 10 parts by mass, preferably 0.1 to 7 parts by mass, per part by mass of magnesium carbonate in order to suppress the unpleasant taste of magnesium carbonate and improve roughness in the oral cavity.

[0020] In the present invention, when bisacodyl and Plantago ovata are blended, the blending amount of Plantago ovata is preferably 105 to 525 parts by mass per 1 part by mass of bisacodyl.

[0021] In the solid preparation of the present invention, an organic acid can be used as an edible acid. For example, organic acids such as citric acid, succinic acid, ascorbic acid, acetic acid, gluconic acid, malic acid, tartaric acid, fumaric acid, adipic acid, etc. can be mentioned, and these can be used alone or in combination of two or more. Among them, citric acid, malic acid, and tartaric acid are preferable. The content of these organic acids is preferably 1 to 70 mass%, more preferably 1 to 50 mass%, even more preferably 1 to 30 mass%, and most preferably 2.4 to 27 mass% based on the total mass of the solid preparation of the present invention. The solid preparation of the present invention is not particularly limited, and examples thereof include medicines, quasi-drugs, foods, etc. Preferred are medicines and quasi-drugs.

[0022] The preparation of the present invention may contain various additives that are generally used as long as they do not impair the effects of the present invention. Examples of such additives include excipients, disintegrants, binders, flow agents, lubricants, acidulants, foaming agents, sweeteners, flavoring agents, flavorings, colorants, surfactants, plasticizers, etc., and from the viewpoint of unpleasant tastes, it is more preferable to contain sweeteners and flavoring agents.

[0023] The dosage form of the present preparation may be, for example, a tablet, a granule, or a powder. These may be solid preparations that are dissolved in water and taken. The tablet of the present invention includes oral disintegrating tablets, chewable tablets, plain tablets, effervescent tablets, dispersible tablets, and dissolving tablets as specified in the General Rules for Preparations of the Japanese Pharmacopoeia.

[0024] Even if the solid preparation of the present invention is a type that is dissolved in water and taken, the unpleasant taste of magnesium salts in saline laxatives is improved.In addition, when the solid preparation of the present invention is a preparation that is taken as it is without water, such as an orally disintegrating tablet or a chewable tablet, or a preparation that is taken in the mouth and then swallowed with water, the roughness in the oral cavity can also be improved.

[0025] The tablet of the present invention may be provided with a score line, a mark for improving identification, or a stamp. Furthermore, the tablet of the present preparation may be a round tablet or an irregular tablet. In addition, in the present invention, from the viewpoint of taste, it is more significant to carry out the present invention in the form of an orally disintegrating tablet, a chewable tablet, a plain tablet, a granule, or a powder. The tablet of the present invention can be manufactured by a conventional tablet manufacturing method. That is, the present preparation can be manufactured by mixing the medicamentous active ingredient and the additives as described above in an appropriate mixer such as a mixer to manufacture a mixed powder for tablets, and then directly compressing the mixed powder into tablets, or by compressing and tableting granules. Granules can be manufactured by dry granulation (slug method, roller compactor method) or wet granulation, and the granulation device may be a roller compactor, stirring granulation method, fluidized bed granulation method, extrusion granulation method, rolling granulation method, spray granulation method, etc. As a machine for compressing and tableting the mixed powder for tablets or the granules of the mixed powder, a single punch tablet machine, a rotary tablet machine, etc. can be used. EXAMPLES

[0026] The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to these examples.

[0027] (Preparation of Formulations) (Examples 1 to 12, Comparative Examples 1 to 8) Each raw material component was weighed according to the composition shown in Tables 1 and 2, and then mixed uniformly. The mixture was mixed with an appropriate amount of a mixture of water and ethanol, kneaded in a mortar, granulated, and then thoroughly dried. The entire amount was then passed through a sieve (mesh opening 500 μm) to obtain granules, which were then divided into 3 packets.

[0028] <Usability test> For each of the preparations of Examples 1 to 12 and Comparative Examples 1 to 8, a sensory evaluation was carried out by two expert panelists. The drug was administered in two ways: by placing a packet of the drug in the mouth and then taking it with water (Method 1), and by dissolving the drug in water and then taking it (Method 2). Each dose was taken with a full glass of water. Method 1 was evaluated for unpleasant taste and roughness, and method 2 was evaluated for unpleasant taste. Unpleasant taste and roughness were evaluated according to the following criteria, and the average scores of the expert panel were calculated.

[0029] <Unpleasant taste> 0: No unpleasant taste 1: Slightly unpleasant taste 2: Slightly unpleasant taste 3: Unpleasant taste 4: Strong unpleasant taste <Roughness> 0: No roughness felt 1: Slightly rough feeling 2: Feels a little rough 3: Feels rough 4: Feels very rough

[0030] The results are shown in Table 1.

[0031] [Table 1]

[0032] [Table 2]

[0033] As shown in Tables 1 and 2, the formulations without Plantago ovata per 1 part by mass of magnesium hydroxide and the formulations with 1 part by mass of Plantago ovata were perceived as having an unpleasant taste and roughness (Comparative Examples 1 to 3). In contrast, the product of the present invention, in which the blending ratio of Plantago ovata was 2 parts by mass per 1 part by mass of magnesium hydroxide, had a reduced unpleasant taste and roughness (Examples 3 and 4). Furthermore, when the formulation was dissolved in water and drunk, no unpleasant taste was felt at all (Examples 3 and 4). When the blending amount of Plantago ovata per 1 part by mass of magnesium hydroxide was increased to 25.4 parts by mass, the unpleasant taste was improved but roughness occurred. Furthermore, the formulation became a lump in the mouth when taken, making it impossible to swallow (Comparative Example 4).

[0034] Furthermore, as shown in Table 1, the unpleasant taste of bisacodyl could be improved by adding Plantago ovata (Examples 5 and 6).

[0035] For magnesium oxide, the roughness was 2 or less in all formulations, but the unpleasant taste tended to decrease with increasing amount of Plantago ovata. Both formulations containing 3.5 parts by mass and 9 parts by mass of Plantago ovata per part by mass of magnesium oxide had an unpleasant taste. On the other hand, when 10 parts by mass or more of Plantago ovata were blended per part by mass of magnesium oxide, the unpleasant taste was improved (Examples 7 to 9, Comparative Examples 6 to 7).

[0036] [Table 3] As shown in Table 3, a formulation containing 0.07 parts by mass of Plantago ovata per part by mass of magnesium sulfate was unable to suppress the unpleasant taste (Comparative Example 8).In contrast, the products of the present invention, which contained 0.14 parts by mass or more of Plantago ovata per part by mass of magnesium sulfate and 0.1 parts by mass or more of Plantago ovata per part by mass of magnesium carbonate, reduced the unpleasant taste and were free of roughness (Examples 10 to 13).

[0037] (Formulation example) (Formulation Examples 1, 2, 4, and 5) The following ingredients and amounts were used in 12 tablets, and they were manufactured in accordance with the General Provisions of the Japanese Pharmacopoeia. (Formulation Examples 3 and 6) The following ingredients and quantities were placed in 6 packets and prepared in accordance with the Japanese Pharmacopoeia General Provisions for Preparations. (Formulation Examples 7 and 8) The following ingredients and amounts were used in 24 tablets, which were manufactured in accordance with the General Provisions of the Japanese Pharmacopoeia.

[0038] Examples of formulations according to the present invention are shown in Table 4 below.

[0039] [Table 4] [Industrial Applicability]

[0040] According to the present invention, a solid preparation in which the unpleasant taste of magnesium salt or bisacodyl of a saline laxative is improved can be provided.

Claims

1. (A) at least one saline laxative selected from magnesium oxide, magnesium hydroxide, magnesium sulfate, and magnesium carbonate; and (B) Plantago ovata, When component (A) is magnesium oxide, the content of component (B) is 10 to 20 parts by mass per part by mass of magnesium oxide (A), When component (A) is magnesium hydroxide, the content of component (B) is 2 to 20 parts by mass per part by mass of magnesium hydroxide (A), When component (A) is magnesium sulfate, the content of component (B) is 0.1 to 5 parts by mass per part by mass of magnesium sulfate (A), When component (A) is magnesium carbonate, the content of component (B) is 0.1 to 10 parts by mass per part by mass of magnesium carbonate (A).

1. A solid formulation for oral administration, comprising:

2. The solid formulation according to claim 1, wherein the content of (B) Plantago ovata is 10 to 95% by mass based on the total mass of the solid formulation.

3. 3. The solid preparation according to claim 1, wherein the content of the magnesium oxide (A) is 1 to 9 mass% based on the total mass of the solid preparation.

4. 3. The solid preparation according to claim 1, wherein the content of the magnesium hydroxide (A) is 5 to 40 mass% based on the total mass of the solid preparation.

5. The solid preparation according to any one of claims 1 to 4, further comprising an organic acid.

6. The solid preparation according to any one of claims 1 to 5, which is in the form of an orally disintegrating tablet, a chewable tablet, a plain tablet, a granule, or a powder.

7. The solid formulation according to any one of claims 1 to 6, wherein (B) Plantago ovata is Plantago ovata seeds or Plantago ovata seed coat.

8. A laxative comprising (A) at least one salt laxative selected from magnesium oxide, magnesium hydroxide, magnesium sulfate, and magnesium carbonate, and (B) Plantago ovata, When component (A) is magnesium oxide, the content of component (B) is 10 to 20 parts by mass per part by mass of magnesium oxide (A), When component (A) is magnesium hydroxide, the content of component (B) is 2 to 20 parts by mass per part by mass of magnesium hydroxide (A), When component (A) is magnesium sulfate, the content of component (B) is 0.1 to 5 parts by mass per part by mass of magnesium sulfate (A), When component (A) is magnesium carbonate, the content of component (B) is 0.1 to 10 parts by mass per part by mass of magnesium carbonate (A). A method for producing a solid preparation for oral administration, comprising the steps of: A method for producing the solid formulation, comprising a step of mixing the component (A) and the Plantago ovata (B).

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