Solid composition

Abstract

To provide a stable solid composition by suppressing decrease in the temporal content of dioctyl sodium sulfosuccinate in a composition comprising at least one selected from magnesium oxide, magnesium hydroxide and magnesium carbonate and dioctyl sodium sulfosuccinate.SOLUTION: There is provided a solid composition comprising (a) at least one selected from magnesium oxide, magnesium hydroxide and magnesium carbonate, (b) dioctyl sodium sulfosuccinate and (c) an organic acid having a solubility in water at 20°C of 1 g / 100 mL or more.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a solid composition containing at least one selected from magnesium oxide, magnesium hydroxide and magnesium carbonate, and dioctyl sodium sulfosuccinate, and more specifically, to a solid pharmaceutical composition in which the decrease in the content of dioctyl sodium sulfosuccinate over time is suppressed. [Background technology]

[0002] Magnesium oxide, magnesium hydroxide, and magnesium carbonate are types of saline laxatives.

[0003] Magnesium oxide becomes poorly absorbed bicarbonate or carbonate in the intestines, and is used as a laxative because it removes water to maintain osmotic pressure and softens the intestinal contents, thereby exerting a laxative effect (Non-Patent Document 1).

[0004] Magnesium hydroxide is neutralized in the stomach to become magnesium chloride, and then reacts with sodium bicarbonate in the intestine to become soluble, poorly absorbed magnesium bicarbonate or magnesium carbonate. In order to maintain the osmotic pressure of the intestinal lumen fluid isotonic, it removes water from the intestinal wall, causing the intestinal contents to retain water, swell, and soften, and when it reaches the large intestine, it renews peristalsis and exerts a laxative effect (Non-Patent Document 2).

[0005] Magnesium carbonate has a saline laxative effect by forming bicarbonate or carbonate in the intestinal tract (Non-Patent Document 3).

[0006] Dioctyl sodium sulfosuccinate has a surfactant effect that reduces the surface tension of stool, allowing water to penetrate the stool to soften it, and causing it to swell, thereby exerting a laxative effect. Therefore, it is called a swelling laxative and is used as a laxative (Non-Patent Document 4).

[0007] Patent Document 1 describes a powder containing magnesium oxide and dioctyl sodium sulfosuccinate, but the powder was used in the test immediately after preparation, and no change over time was observed. Therefore, no decrease in the content of dioctyl sodium sulfosuccinate was confirmed, and it is unclear whether any change over time has occurred.

[0008] So far, no preparation containing at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate, and dioctyl sodium sulfosuccinate has been commercially available. The present inventors produced a composition containing at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate, and dioctyl sodium sulfosuccinate, but were faced with the problem that the content of dioctyl sodium sulfosuccinate decreased over time. Furthermore, no technical report has been published regarding the stability of dioctyl sodium sulfosuccinate. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Patent Publication 2001-199894 [Non-patent literature]

[0010] [Non-Patent Document 1] Commentary on the 17th revised Japanese Pharmacopoeia, Hirokawa Publishing Co., Ltd., page C-1982 [Non-Patent Document 2] Pharmaceutical Interview Form Milmag, Milmag Tablets [Non-Patent Document 3] Commentary on the 17th revised Japanese Pharmacopoeia, Hirokawa Publishing Co., Ltd., page C-3007 [Non-Patent Document 4] OTC Handbook 2002-03, page 380 Summary of the Invention [Problem to be solved by the invention]

[0011] An object of the present invention is to provide a stable solid composition containing dioctyl sodium sulfosuccinate and at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate, which inhibits a decrease in the content of dioctyl sodium sulfosuccinate over time. [Means for solving the problem]

[0012] As a result of intensive research aimed at solving the above-mentioned problems, the inventors discovered that the decrease in dioctyl sodium sulfosuccinate over time can be suppressed by adding an organic acid having a solubility of 1 g / 100 mL or more in water at 20°C, and thus completed the present invention.

[0013] That is, the present invention provides (1) A solid composition comprising: (a) at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate; (b) dioctyl sodium sulfosuccinate; and (c) an organic acid having a solubility in water at 20° C. of 1 g / 100 mL or more. (2) (c) the solid composition according to (1), wherein the organic acid is at least one selected from the group consisting of citric acid, tartaric acid, malic acid, ascorbic acid and succinic acid; (3) (a) The solid composition according to (1) or (2), characterized in that the magnesium oxide is heavy magnesium oxide. (4) (a) The solid composition according to (1) or (2), characterized in that the magnesium carbonate is heavy magnesium carbonate. (5) The solid composition according to any one of (1) to (4), characterized in that (a) at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate, and (b) dioctyl sodium sulfosuccinate are contained in different granules. (6) A method for suppressing a decrease in the content of dioctyl sodium sulfosuccinate in a solid composition comprising (a) at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate, and (b) dioctyl sodium sulfosuccinate, the method comprising the step of: (c) containing an organic acid having a solubility of 1 g / 100 mL or more in water at 20° C.; It is. Effect of the Invention

[0014] According to the present invention, it is possible to provide a pharmaceutical composition which contains at least one selected from magnesium oxide, magnesium hydroxide and magnesium carbonate, as well as dioctyl sodium sulfosuccinate, and which inhibits a decrease in the dioctyl sodium sulfosuccinate content. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] In the present invention, at least one type selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate (hereinafter, sometimes referred to as "component (a)") is one that is described in the Japanese Pharmacopoeia or the Japanese Pharmacopoeia Non-Pharmacopoeial Pharmaceutical Standards, and can be produced by known methods, or a commercially available product can be used.

[0016] Magnesium oxide is generally classified into light magnesium oxide and heavy magnesium oxide, and in the field of pharmaceuticals, light magnesium oxide is often used as an excipient, and heavy magnesium oxide is often used as an active ingredient. Heavy magnesium oxide refers to magnesium oxide having a volume of 30 mL or less per 5 g of magnesium oxide, for example, Japanese Pharmacopoeia Magnesium Oxide Heavy (manufactured by Kyowa Chemical Industry Co., Ltd.) and Japanese Pharmacopoeia Magnesium Oxide Granules (manufactured by Kyowa Chemical Industry Co., Ltd.). Light magnesium oxide refers to magnesium oxide having a volume of 30 mL or more per 5 g of magnesium oxide, for example, Japanese Pharmacopoeia Magnesium Oxide Light (manufactured by Kyowa Chemical Industry Co., Ltd.). The magnesium oxide in the present invention is preferably magnesium oxide having a volume of 30 mL or less per 5 g of magnesium oxide, that is, heavy magnesium oxide. Light magnesium oxide requires careful handling because it has a light density and is easily scattered during production, while heavy magnesium oxide is easy to handle during production.

[0017] Magnesium carbonate is generally classified into light magnesium carbonate and heavy magnesium carbonate, and in the field of pharmaceuticals, light magnesium carbonate is often used as an excipient, and heavy magnesium carbonate is often used as an active ingredient. Heavy magnesium carbonate refers to magnesium carbonate that is below the 12.0 mL mark when performing the sedimentation test described in the Japanese Pharmacopoeia, 17th Edition, and for example, Japanese Pharmacopoeia Magnesium Carbonate Heavy (manufactured by Kyowa Chemical Industry Co., Ltd.). Light magnesium carbonate refers to magnesium carbonate that is above the 12.0 mL mark when performing the sedimentation test described in the Japanese Pharmacopoeia, 17th Edition, and for example, Japanese Pharmacopoeia Magnesium Carbonate Light (manufactured by Kyowa Chemical Industry Co., Ltd.). The magnesium carbonate in the present invention is preferably magnesium carbonate that is below the 12.0 mL mark when performing the sedimentation test, that is, heavy magnesium carbonate. Light magnesium carbonate requires careful handling because it has a light density and is easily scattered during production, while heavy magnesium carbonate is easy to handle during production.

[0018] The content of (a) at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate in the solid composition of the present invention (when a plurality of (a) components are contained, the total amount thereof, the same applies hereinafter) is not particularly limited as long as it is an amount that exhibits its medicinal effect, but is usually 20 to 95% by mass, and preferably 40 to 90% by mass.

[0019] The (b) dioctyl sodium sulfosuccinate (hereinafter, sometimes referred to as "DSS" or "component (b)") in the present invention can be obtained as a commercially available product or produced by a known production method.

[0020] The content of component (b) in the solid composition of the present invention is not particularly limited as long as it is an amount that exhibits its medicinal effect, but is usually 0.01 to 20% by mass, preferably 0.1 to 10% by mass.

[0021] The organic acid (c) having a solubility of 1 g / 100 mL or more in water at 20° C. (hereinafter, sometimes referred to as “component (c)”) in the present invention can be obtained commercially or produced by a known production method. Examples of the organic acid (c) having a solubility of 1 g / 100 mL or more in water at 20° C. in the present invention include citric acid, tartaric acid, malic acid, ascorbic acid, succinic acid, and oxalic acid, and preferably citric acid, tartaric acid, malic acid, ascorbic acid, and succinic acid. The solubility in water at 20° C. is measured and calculated according to the method described in the general rules for solubility in the 17th revised Japanese Pharmacopoeia. That is, the solubility in water at 20° C. refers to the degree to which a solid is dissolved within 30 minutes when it is powdered, placed in a solvent, and vigorously shaken for 30 seconds at 20° C. every 5 minutes.

[0022] The content of the (c) component in the solid composition of the present invention (when a plurality of (c) components are included, the total amount thereof, the same applies below) is not particularly limited, but is usually 0.01 to 20% by mass, preferably 0.1 to 10% by mass. The content of the (c) component is usually 0.1 to 5 parts by mass, preferably 0.3 to 3 parts by mass, and more preferably 0.5 to 2 parts by mass relative to 1 part by mass of the dioctyl sodium sulfosuccinate, and is usually 0.0001 to 0.1 parts by mass, preferably 0.0005 to 0.07 parts by mass, and more preferably 0.001 to 0.05 parts by mass relative to 1 part by mass of the (a) component. The content of the dioctyl sodium sulfosuccinate is usually 0.0001 to 100 parts by mass, preferably 0.0003 to 10 parts by mass, and more preferably 0.0005 to 5 parts by mass, and particularly preferably 0.001 to 1 part by mass relative to 1 part by mass of the (a) component.

[0023] The solid composition of the present invention refers to a composition that is solid at room temperature and is composed of two or more components, and examples thereof include powder obtained by mixing, granules obtained by granulation, and tablets obtained by tableting powders or granules, and is preferably a solid composition for oral administration. The dosage form is not particularly limited, and examples thereof include tablets, granules, powders, fine granules, pills, capsules, chewable tablets, orally disintegrating tablets, or dry syrups, and is preferably tablets, granules, or powders.

[0024] The pharmaceutical composition of the present invention may contain other commonly used active ingredients, excipients, disintegrants, binders, lubricants, colorants, flavorings, fragrances, coating agents, and the like, within the qualitative and quantitative ranges that do not impair the effects of the present invention.

[0025] Other active ingredients that can be incorporated into the pharmaceutical composition of the present invention include, for example, vitamins, anti-inflammatory agents, gastric mucosa protective agents, herbal medicines, Chinese herbal medicine prescriptions, caffeine, etc., and the pharmaceutical composition may contain one or more types selected from the group consisting of these.

[0026] Examples of excipients that can be incorporated into the pharmaceutical composition of the present invention include lactose, starches, crystalline cellulose, sucrose, sugar alcohols, calcium hydrogen phosphate, etc., examples of binders include hydroxypropylcellulose, hypromellose, pregelatinized starch, polyvinylpyrrolidone, pullulan, etc., examples of flow agents include light anhydrous silicic acid, hydrated silicon dioxide, aluminum silicate, etc., examples of lubricants include stearic acid, magnesium stearate, calcium stearate, talc, sucrose fatty acid esters, sodium stearyl fumarate, sucrose fatty acid esters, hardened oils, etc., examples of disintegrants include carboxymethylcellulose, carboxymethylcellulose calcium, carboxymethylstarch sodium, croscarmellose sodium, croscarmellose calcium, crospovidone, low-substituted hydroxypropylcellulose, hydroxypropylstarch, etc.

[0027] The solid composition of the present invention can be produced by a method generally used in the formulation of pharmaceuticals, and can be appropriately mixed with ingredients that are generally mixed during the preparation of pharmaceuticals within a range that does not impair the effects of the present invention. For example, the solid composition can be produced by mixing the (a) component, the (b) component, and the (c) component, and, if necessary, mixing other known additives such as excipients, disintegrants, binders, lubricants, antioxidants, coating agents, colorants, flavoring agents, surfactants, plasticizers, etc., in a conventional manner.

[0028] In addition, when granulation is performed during production, the granulation method is not particularly limited, and can be produced by wet granulation, dry granulation, melt granulation, etc., but is preferably wet granulation. The above-mentioned additives may be appropriately mixed with the obtained granulated particles, and the mixture thus obtained can be compressed into tablets. When producing tablets, they may be produced by direct compression.

[0029] The solid composition of the present invention may be any form in which the (a), (b) and (c) components are mixed, and the effects of the present invention are exhibited. For example, the (a), (b) and (c) components may be mixed at the same time with other excipients added as necessary, and then granulated or tableted, or granulated particles each containing each of the above components alone may be mixed. In addition, granulated particles containing the (a) and (b) components may be mixed with the (c) component, granulated particles containing the (a) and (c) components may be mixed with the (b) component, or granulated particles containing the (b) and (c) components may be mixed with the (a) component. Of these, a preferred form is a solid composition containing granulated particles containing the (b) and (c) components and granulated particles containing the (a) component. EXAMPLES

[0030] 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 the following examples in any way. (Control Example 1, Comparative Examples 1 to 7, Examples 1 to 8) A powder was prepared according to the formulation shown in Table 1. Dioctyl sodium sulfosuccinate and an organic acid were dissolved or dispersed in a mixed solution of water and ethanol to obtain a solution or dispersion. The solution or dispersion was added to crystalline cellulose (for granulation) and dried to obtain granules. The obtained granules were mixed with magnesium oxide, magnesium hydroxide, magnesium carbonate or magnesium sulfate, and crystalline cellulose (for subsequent powder addition) to prepare a solid composition. (Test Example 1) Control Example 1, Comparative Examples 1 to 7, and Examples 1 to 8 were placed in glass bottles, sealed, and stored for 7 days at 65° C. After storage, the dioctyl sodium sulfosuccinate content in each solid composition was measured to determine the residual rate (%).

[0031] [Table 1]

[0032] As is clear from Table 1, the DSS content was significantly reduced in Comparative Examples 1 and 2 in which magnesium oxide was blended, compared to Control Example 1. The addition of citric acid, tartaric acid, malic acid, ascorbic acid or succinic acid to magnesium oxide and DSS improved the residual rate of DSS compared to Comparative Example 1 or 2 (Examples 1 to 6). On the other hand, when fumaric acid (Comparative Example 3) was added, the residual rate of DSS was lower than that of Comparative Example 1 or 2. In Comparative Example 4 in which magnesium hydroxide was added, the residual rate of DSS was significantly reduced, but by adding citric acid, the residual rate of DSS was improved compared to Comparative Example 4 (Example 7). In Comparative Example 5 in which magnesium carbonate was added, the DSS residual rate was significantly reduced, but by adding citric acid, the DSS residual rate was improved compared to Comparative Example 5 (Example 8). In Comparative Example 6 in which magnesium sulfate was blended, the DSS residual rate decreased, but by adding citric acid, the DSS residual rate decreased further than in Comparative Example 6 (Comparative Example 7).

[0033] (Formulation Example 1) Tablets were prepared according to the recipe shown in Table 2. Dioctyl sodium sulfosuccinate and citric acid were dissolved in a mixed solution of water and ethanol to prepare a solution. The solution was added to calcium hydrogen phosphate and dried to prepare granules. The obtained granules were mixed with other ingredients and molded using a rotary tablet press to prepare tablets. The prepared tablets were stored in a sealed glass bottle together with a desiccant such as a zeolite-containing desiccant (MS-Tablet-W, MS-Ceramu-W; Tokai Chemical Industry Co., Ltd.), a silica gel-containing desiccant (Sivelet AS-W, Tokai Chemical Industry Co., Ltd.), or a calcium chloride-containing desiccant (Alp Sheet, Tokai Chemical Industry Co., Ltd.), and in the case of PTP packaging, the PTP-packaged tablets were packaged together with the desiccant in an aluminum pillow or aluminum pouch and stored. In addition, when the desiccant was not used, the tablets were filled and packaged in a PTP sheet, aluminum pillow, aluminum pouch, etc. that has the ability to absorb and retain moisture, and stored.

[0034] [Table 2] [Industrial Applicability]

[0035] The present invention makes it possible to provide a solid composition which simultaneously contains at least one selected from magnesium oxide, magnesium hydroxide and magnesium carbonate, and dioctyl sodium sulfosuccinate, and which inhibits a decrease in the dioctyl sodium sulfosuccinate content over time.

Claims

1. A solid composition comprising: (a) at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate; (b) dioctyl sodium sulfosuccinate; and (c) an organic acid having a solubility in water at 20°C of 1 g / 100 mL or more.

2. 2. The solid composition according to claim 1, wherein the organic acid (c) is at least one selected from the group consisting of citric acid, tartaric acid, malic acid, ascorbic acid and succinic acid.

3. 3. The solid composition according to claim 1 or 2, characterized in that the magnesium oxide (a) is heavy magnesium oxide.

4. 3. The solid composition according to claim 1 or 2, characterized in that the (a) magnesium carbonate is heavy magnesium carbonate.

5. 5. The solid composition according to claim 1, wherein (a) at least one selected from magnesium oxide, magnesium hydroxide and magnesium carbonate, and (b) dioctyl sodium sulfosuccinate are contained in different granules.

6. A method for suppressing a decrease in the content of (b) dioctyl sodium sulfosuccinate in a solid composition containing (a) at least one selected from magnesium oxide, magnesium hydroxide, and magnesium carbonate, and (b) dioctyl sodium sulfosuccinate, the method being characterized by containing (c) an organic acid having a solubility in water at 20°C of 1 g / 100 mL or more.

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