Oral pharmaceutical composition

Abstract

To provide a pharmaceutical composition for oral use that contains itopride and / or a salt thereof, and has the effect of preventing or improving stool abnormality.SOLUTION: A pharmaceutical composition for oral use contains (A) itopride and / or a salt thereof and (B) at least one selected from the group consisting of aldioxa, glutamine, teprenone, and sucralfate hydrate.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an oral pharmaceutical preparation containing itopride and / or a salt thereof, which has the effect of preventing or improving abnormal bowel movements. [Background technology]

[0002] Itopride and its salts have an antagonistic effect on dopamine D2 receptors, and by releasing acetylcholine and inhibiting acetylcholinesterase, they stimulate gastrointestinal motility in the stomach, and are therefore used to improve gastrointestinal symptoms (abdominal bloating, upper abdominal pain, loss of appetite, heartburn, nausea, vomiting, etc.) associated with functional dyspepsia and chronic gastritis.

[0003] Although itopride and its salts are relatively safe drugs, a certain number of side effects such as bowel movement disorders, such as diarrhea and constipation, have been reported (see Non-Patent Document 1). Furthermore, patients suffering from functional dyspepsia or chronic gastritis may also have bowel movement disorders. Therefore, in order to enhance the usefulness of an oral pharmaceutical composition containing itopride or a salt thereof, it is desirable that the composition have the effect of preventing or improving bowel movement disorders. Furthermore, in recent years, the number of people complaining of bowel movement disorders due to poor diet, irregular lifestyle habits, excessive stress, etc. has been increasing, and there is a need for the development of a new oral pharmaceutical composition that can prevent or improve bowel movement disorders. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Pharmaceutical Interview Form Gastrointestinal Motility Stimulant Ganaton R Tablets 50mg, Mylan EPD LLC, October 2021 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide an oral pharmaceutical product containing itopride and / or a salt thereof, which has the effect of preventing or improving abnormal bowel movements. [Means for solving the problem]

[0006] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that the incorporation of at least one compound selected from the group consisting of aldioxa, glutamine, teprenone, and sucralfate hydrate in an oral pharmaceutical composition containing itopride and / or a salt thereof can prevent or improve at least one symptom of abnormal bowel movements. More specifically, the inventors have found that an oral pharmaceutical composition containing itopride and / or a salt thereof and aldioxa and / or glutamine can prevent or improve constipation. The inventors have also found that an oral pharmaceutical composition containing itopride and / or a salt thereof and teprenone can prevent or improve constipation and diarrhea. The inventors have also found that an oral pharmaceutical composition containing itopride and / or a salt thereof and sucralfate hydrate can prevent or improve diarrhea. The present invention was completed through further research based on these findings.

[0007] That is, the present invention provides the following aspects. Item 1. (A) Itopride and / or its salt, and (B) at least one selected from the group consisting of aldioxa, glutamine, teprenone, and sucralfate hydrate An oral pharmaceutical composition comprising: Item 2. The pharmaceutical composition for oral administration according to Item 1, wherein the component (B) is aldioxa, and the composition contains 0.1 to 5 parts by weight of aldioxa per 1 part by weight of itopride and / or a salt thereof. Item 3. The pharmaceutical composition for oral administration according to Item 1, wherein the component (B) is glutamine and contains 0.1 to 20 parts by weight of glutamine per part by weight of itopride and / or a salt thereof. Item 4. The oral pharmaceutical composition according to Item 1, wherein the component (B) is teprenone and contains 0.1 to 3 parts by weight of teprenone per 1 part by weight of itopride and / or a salt thereof. Item 5. The pharmaceutical composition for oral administration according to Item 1, wherein the component (B) is sucralfate hydrate, and the composition contains 0.25 to 25 parts by weight of sucralfate hydrate per 1 part by weight of itopride and / or a salt thereof. [Effects of the Invention]

[0008] According to the present invention, by combining itopride and / or a salt thereof with at least one selected from the group consisting of aldioxa, glutamine, teprenone, and sucralfate hydrate in an oral pharmaceutical, it is possible to provide an oral pharmaceutical having the effect of preventing or improving bowel movement disorders. DETAILED DESCRIPTION OF THE INVENTION

[0009] The pharmaceutical composition of the present invention is characterized by containing itopride and / or a salt thereof (sometimes referred to as component (A)), and at least one member selected from the group consisting of aldioxa, glutamine, teprenone, and sucralfate hydrate (sometimes referred to as component (B)). The oral composition of the present invention is described in detail below.

[0010] [Component (A)] The oral pharmaceutical composition of the present invention contains itopride and / or a salt thereof as component (A). Itopride is a known component that acts on dopamine D2 receptors to promote the release of acetylcholine and inhibits the degradation of acetylcholine, thereby activating gastrointestinal motility in the stomach.

[0011] The salt of itopride is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, nitrate, phosphate, etc.; and organic acid salts such as acetate, maleate, fumarate, malate, citrate, oxalate, lactate, tartrate, etc. Of these salts, inorganic acid salts are preferred, and hydrochloride is more preferred.

[0012] In the oral pharmaceutical composition of the present invention, one kind selected from itopride and salts thereof may be used alone as component (A), or two or more kinds may be used in combination.

[0013] Of the components (A), salts of itopride are preferred, and itopride hydrochloride is more preferred.

[0014] The content of component (A) in the oral pharmaceutical composition of the present invention may be appropriately set depending on the dosage form, dosage amount, etc., and may be, for example, 1 to 75% by weight, preferably 2 to 50% by weight, more preferably 2 to 40% by weight, and even more preferably 3 to 30% by weight.

[0015] [(B) Component] The oral pharmaceutical composition of the present invention contains at least one selected from the group consisting of aldioxa, glutamine, teprenone, and sucralfate hydrate as component (B). It is known that itopride and its salts can cause abnormal bowel movements as a side effect, but when used in combination with aldioxa, glutamine, teprenone, and / or sucralfate hydrate, it is possible to achieve the effect of preventing or improving abnormal bowel movements.

[0016] Aldioxa Aldioxa is an aluminum dihydroxide salt of allantoin obtained by condensing allantoin with aluminum hydroxide, and is a known ingredient used as a therapeutic agent for gastritis, peptic ulcers, etc. It is known that both itopride and / or its salts and aldioxa can cause constipation as a side effect, but in the present invention, by using them in combination, it is possible to achieve the effect of preventing or improving constipation.

[0017] When aldioxa is used as component (B), the ratio of itopride and / or a salt thereof to aldioxa is, for example, 0.1 to 5 parts by weight of aldioxa per 1 part by weight of itopride and / or a salt thereof. From the viewpoint of further improving the effect of preventing or improving constipation, the ratio of aldioxa per 1 part by weight of itopride and / or a salt thereof is preferably 0.2 to 5 parts by weight, more preferably 0.3 to 3 parts by weight, and even more preferably 0.4 to 2.5 parts by weight.

[0018] Furthermore, when aldioxa is used as component (B), the content of aldioxa in the oral pharmaceutical composition of the present invention may be appropriately set depending on the dosage form, dosage amount, the above ratio, etc., and may be, for example, 1 to 70% by weight, preferably 2 to 60% by weight, more preferably 3 to 50% by weight, and even more preferably 5 to 50% by weight.

[0019] ·glutamine Glutamine is a type of amino acid that has the effect of protecting the gastric mucosa and is a known component used as a therapeutic agent for peptic ulcers, etc. As mentioned above, it is known that itopride and / or a salt thereof can cause constipation as a side effect, but in the present invention, the combined use of itopride and / or a salt thereof with glutamine can achieve the effect of preventing or improving constipation.

[0020] Glutamine may be in the L-, D-, or DL-form, but is preferably in the L-form.

[0021] When glutamine is used as component (B), the ratio of itopride and / or a salt thereof to glutamine is, for example, 0.1 to 20 parts by weight of glutamine per 1 part by weight of itopride and / or a salt thereof. From the viewpoint of further improving the effect of preventing or improving constipation, the ratio of glutamine per 1 part by weight of itopride and / or a salt thereof is preferably 1 to 20 parts by weight, more preferably 2 to 18 parts by weight, and even more preferably 2.5 to 14 parts by weight.

[0022] Furthermore, when glutamine is used as component (B), the content of glutamine in the oral pharmaceutical composition of the present invention may be appropriately set depending on the dosage form, dosage amount, the ratio, etc., and may be, for example, 5 to 95% by weight, preferably 10 to 95% by weight, more preferably 20 to 93% by weight, and even more preferably 25 to 90% by weight.

[0023] Teprenone Teprenone is a defense factor-enhancing antiulcer drug and is a known component of a therapeutic agent for gastritis and gastric ulcers used to improve gastric mucosal lesions during acute exacerbations of acute gastritis and chronic gastritis, and to treat gastric ulcers, etc. It is known that both itopride and / or its salts and teprenone can cause constipation and diarrhea as side effects, but in the present invention, their combined use can achieve the effect of preventing or improving constipation and diarrhea.

[0024] When teprenone is used as component (B), the ratio of itopride and / or a salt thereof to teprenone is, for example, 0.1 to 3 parts by weight of teprenone per 1 part by weight of itopride and / or a salt thereof. From the viewpoint of further improving the effect of preventing or improving constipation, the ratio of teprenone per 1 part by weight of itopride and / or a salt thereof is preferably 0.1 to 2 parts by weight, more preferably 0.2 to 1.5 parts by weight, and even more preferably 0.5 to 1 part by weight.

[0025] Furthermore, when teprenone is used as component (B), the content of teprenone in the oral pharmaceutical composition of the present invention may be appropriately set depending on the dosage form, dosage amount, the ratio, etc., and may be, for example, 2 to 60% by weight, preferably 3 to 50% by weight, more preferably 4 to 50% by weight, and even more preferably 5 to 40% by weight.

[0026] Sucralfate hydrate Sucralfate hydrate has gastric mucosa-protecting, antipepsin, and antacid effects, and is a known ingredient used as a therapeutic agent for gastritis and peptic ulcers. As mentioned above, it is known that itopride and / or its salts can cause diarrhea as a side effect. However, in the present invention, the combined use of itopride and / or its salts with sucralfate hydrate can achieve the effect of preventing or improving diarrhea.

[0027] When sucralfate hydrate is used as component (B), the ratio of itopride and / or a salt thereof to sucralfate hydrate is, for example, 0.25 to 25 parts by weight of sucralfate hydrate per part by weight of itopride and / or a salt thereof. From the viewpoint of further improving the effect of preventing or improving constipation, the ratio of sucralfate hydrate per part by weight of itopride and / or a salt thereof is preferably 0.5 to 20 parts by weight, more preferably 1 to 15 parts by weight, and even more preferably 5 to 15 parts by weight.

[0028] When sucralfate hydrate is used as component (B), the content of sucralfate hydrate in the oral pharmaceutical composition of the present invention may be appropriately determined depending on the dosage form, dosage amount, the above-mentioned ratio, etc., and may be, for example, 30 to 95% by weight, preferably 40 to 85% by weight, more preferably 50 to 75% by weight, and even more preferably 60 to 75% by weight.

[0029] [Other ingredients] The oral pharmaceutical composition of the present invention may contain other pharmacological ingredients, if necessary, in addition to the above-mentioned ingredients. The types of such pharmacological ingredients are not particularly limited, and examples include anti-inflammatory analgesics, digestives, antispasmodics, mucosal repair agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, hypnotics and sedatives, antihistamines, cardiac diuretics, antibacterial agents, antacids, acid secretion inhibitors, vasodilators, proton pump inhibitors, herbal medicines, herbal extracts, caffeines, menthols, polyphenols, and the like. These pharmacological ingredients may be used alone or in combination of two or more. The content of these pharmacological ingredients may be appropriately determined depending on the type of pharmacological ingredient used and the dosage form of the oral pharmaceutical composition.

[0030] The pharmaceutical composition of the present invention may contain pharmaceutically acceptable bases and additives, as necessary, to prepare it into the desired dosage form. Examples of such bases and additives include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, preservatives, flavoring agents, fragrances, powders, thickeners, dyes, and chelating agents. These bases and additives may be used alone or in combination of two or more. The content of these bases and additives may be appropriately determined depending on the type of added ingredient used and the dosage form of the oral pharmaceutical composition.

[0031] [Dosage form] The dosage form of the oral pharmaceutical composition of the present invention is not particularly limited, and may be any of a solid preparation, a semi-solid preparation, or a liquid preparation.

[0032] Specific examples of solid preparations include tablets, pills, capsules (soft capsules, hard capsules), powders, granules (including dry syrups), etc. Specific examples of semi-solid preparations include jellies, etc. Specific examples of liquid preparations include solutions, suspensions, syrups, etc.

[0033] Among these dosage forms, solid preparations are preferred.

[0034] To prepare the oral pharmaceutical composition of the present invention into the above dosage form, the composition may be formulated using component (A), component (B), and other pharmacological ingredients, bases, and additives that are added as needed, according to conventional formulation techniques used in the pharmaceutical field.

[0035] [Dosage and administration] The oral pharmaceutical composition of the present invention can be used for the purpose of preventing or improving at least one symptom of abnormal bowel movements (constipation, diarrhea). In addition, since itopride and / or a salt thereof contained in the oral pharmaceutical composition of the present invention has an effect of preventing or improving gastrointestinal symptoms (abdominal bloating, upper abdominal pain, loss of appetite, heartburn, nausea, vomiting, etc.) and stomach pain associated with functional dyspepsia or chronic gastritis, the oral pharmaceutical composition of the present invention can also be used for the purpose of preventing or improving abnormal bowel movements while preventing or improving the symptoms in a person with such symptoms.

[0036] Furthermore, the bowel abnormalities that are the target of prevention or improvement by the oral pharmaceutical composition of the present invention are constipation or diarrhea, and the oral pharmaceutical composition of the present invention can be used for the purpose of preventing or improving constipation when aldioxa and / or glutamine are used as component (B), for the purpose of preventing or improving constipation when teprenone is used as component (B), and for the purpose of preventing or improving diarrhea when sucralfate hydrate is used as component (B).

[0037] The dosage of the oral pharmaceutical composition of the present invention may be appropriately determined depending on the intended use, the age of the recipient, etc., but may be, for example, administered 1 to 3 times per day such that the daily dose of itopride and / or a salt thereof is about 1 to 300 mg, preferably about 50 to 150 mg, and more preferably about 100 to 150 mg. [Example]

[0038] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0039] Test Example 1: Verification of the preventive or ameliorative effects of combined use of itopride hydrochloride and aldioxa or L-glutamine on constipation The efficacy of loperamide-induced constipation in preventing or improving constipation was evaluated using a rat model of loperamide-induced constipation, a commonly used constipation model. Specifically, 8-week-old male rats (Slc:SD) were divided into seven groups (Table 1). Each group was administered 5 mL / kg of the designated test substance by oral gavage using an oral gavage tube. One hour after administration of the test substance, loperamide hydrochloride was administered at 1 mg / kg by oral gavage using an oral gavage tube. The rats were housed under normal conditions from the time of loperamide hydrochloride administration until 7 hours after administration, during which time the number of feces and wet feces weight were measured. Feces were collected approximately once every hour, and the wet feces weight was measured each time. The mean and standard deviation for each group were calculated from the total number of feces and wet feces weight for each group up to 7 hours after administration, and statistical analysis was performed between groups. The rats were raised in an atmosphere of 20-26°C and humidity of 40-70%RH. Under these collection conditions, the measured value of the fecal (wet) weight was not significantly affected by natural drying between excretion and collection.

[0040] [Table 1]

[0041] The results are shown in Table 2. In the control group, the number of feces and feces (wet) weight were significantly reduced compared to the untreated group, confirming that the administration of loperamide hydrochloride induced constipation symptoms. In the itopride alone group, there was no significant difference compared to the control group, and almost no effect on preventing or improving constipation was observed. In the aldioxa alone group, the number of feces and feces (wet) weight were slightly increased compared to the control group, indicating a slight tendency for constipation symptoms to worsen. Furthermore, in the L-glutamine alone group, the number of feces and feces (wet) weight were similar to those in the control group, and no effect on preventing or improving constipation was observed.

[0042] In contrast, the fecal count and wet fecal weight in the itopride / aldioxa combination group and the itopride / L-glutamine combination group were significantly increased compared to the control group, reaching levels comparable to those in the untreated group. This demonstrates that the combined use of itopride hydrochloride with aldioxa or L-glutamine is effective in preventing or alleviating constipation.

[0043] [Table 2]

[0044] Test Example 2: Verification of the preventive or ameliorative effects of combined use of itopride hydrochloride and teprenone on diarrhea The preventive or ameliorative effects of castor oil-induced diarrhea were evaluated using a rat model of diarrhea, a commonly used diarrhea model. Specifically, 6- to 7-week-old male rats (crl:CD(SD)) were divided into five groups as shown in Table 3. Each group was administered the designated test substance at 5 mL / kg by oral gavage using an oral gavage tube. One hour after administration of the test substance, castor oil was administered at 0.5 mL / head by oral gavage using an oral gavage tube. The rats were housed under normal conditions from the time of castor oil administration until 24 hours later, during which time the moisture content of their feces was measured. The moisture content of the feces was calculated by measuring the wet weight of the feces, drying the feces at 80-90°C for 12 hours, and then measuring the dry weight of the feces. The dry weight of the feces was then subtracted from the wet weight of the feces. Feces were collected approximately every hour for the first 8 hours after castor oil administration, and then collected at 24 hours thereafter, with fecal moisture content measured each time. The mean and standard deviation for each group were calculated from the total fecal moisture content up to 24 hours after administration, and statistical analysis was performed between groups. Rats were housed in an atmosphere of 20-26°C and 40-70% RH. Under these collection conditions, the measured fecal (wet) weight was not significantly affected by natural drying between excretion and collection.

[0045] [Table 3]

[0046] The results are shown in Table 4. In this study, there was almost no difference in the total dry weight of feces collected over 24 hours between the groups. In the control group, fecal moisture content was significantly increased compared to the untreated group, confirming that castor oil administration induced diarrhea. In the itopride-only group, fecal moisture content was slightly higher than in the control group, indicating a tendency for diarrhea symptoms to worsen. In the teprenone-only group, fecal moisture content was slightly decreased compared to the control group, but no significant difference was observed between these groups.

[0047] In contrast, the fecal moisture content in the itopride / teprenone combination group was significantly lower than that in the control group, reaching the same level as that in the untreated group. This indicates that the combined use of itopride hydrochloride and teprenone is effective in preventing or ameliorating diarrhea.

[0048] [Table 4]

[0049] Test Example 3: Verification of the preventive or ameliorative effect of constipation by combined use of itopride hydrochloride and teprenone The efficacy of loperamide-induced constipation in preventing or ameliorating constipation was evaluated using a rat model of loperamide-induced constipation, a commonly used constipation model. Specifically, 8-week-old male rats (Slc:SD) were divided into five groups (Table 5). Each group received 5 mL / kg of the designated test substance via oral gavage. One hour after administration of the test substance, loperamide hydrochloride was administered at 1 mg / kg via oral gavage via oral gavage. The rats were housed under normal conditions from the time of loperamide hydrochloride administration until 24 hours later, during which fecal counts and wet fecal weights were measured. Fecal samples were collected approximately every hour for the first 8 hours after loperamide hydrochloride administration, and then collected at 24 hours thereafter. Fecal counts and wet fecal weights were measured at each collection. The mean and standard deviation for each group were calculated from the total fecal counts and wet fecal weights for each group up to 24 hours later, and statistical analysis was performed between groups. The rats were raised in an atmosphere of 20-26°C and humidity of 40-70%RH. Under these collection conditions, the measured value of the fecal (wet) weight was not significantly affected by natural drying between excretion and collection.

[0050] [Table 5]

[0051] The results are shown in Table 6. In the control group, the number of feces and feces (wet) weight were significantly reduced compared to the untreated group, confirming that the administration of loperamide hydrochloride induced constipation symptoms. The number of feces and feces (wet) weight in the itopride-only group were slightly increased compared to the control group, but no significant difference was observed between the two groups. The number of feces and feces (wet) weight in the teprenone-only group were similar to those in the control group, and no effect on preventing or improving constipation was observed.

[0052] In contrast, the fecal count and fecal (wet) weight in the itopride / teprenone combination group were significantly increased compared to the control group and were comparable to those in the untreated group. This demonstrates that the combined use of itopride hydrochloride and teprenone has an excellent effect in preventing or improving constipation. Taking into account the results of Test Example 2, the combined use of itopride hydrochloride and teprenone is effective in preventing or improving both diarrhea and constipation, and is therefore effective in preventing or improving bowel movement disorders in general. [Table 6]

[0053] Test Example 4: Verification of the preventive or ameliorative effects of combined use of itopride hydrochloride and sucralfate hydrate on diarrhea The preventive or ameliorative effects of castor oil-induced diarrhea were evaluated using a rat model of diarrhea, a commonly used diarrhea model. Specifically, 6- to 7-week-old male rats (crl:CD(SD)) were divided into five groups as shown in Table 7. Each group was given a 5 mL / kg dose of the designated test substance by oral gavage using an oral gavage tube. One hour after administration of the test substance, castor oil was given at 0.5 mL / head by oral gavage using an oral gavage tube. The rats were housed under normal conditions from the time of castor oil administration until 24 hours later, during which time the moisture content of the feces was measured and the quality of the feces was evaluated. The moisture content of the feces was calculated by measuring the wet weight of the feces, drying the feces at 80-90°C for 12 hours, and then measuring the dry weight. The dry weight of the feces was then subtracted from the wet weight of the feces. The fecal properties were evaluated by observing the appearance of the feces of each individual and determining whether they were normal, abnormal (loose stool (soft stool that retained some of its original shape), diarrheal stool (liquid or nearly liquid stool with a high water content), or watery stool (almost watery stool, softened by a large amount of serous fluid)), and the percentage (%) of individuals with normal stool was calculated. Feces were collected approximately once every hour for up to 8 hours after administration of castor oil, and then collected at 24 hours thereafter. The test was performed, and the fecal moisture content was measured and the fecal properties were evaluated each time. The mean and standard deviation for each group were calculated from the total fecal moisture content up to 24 hours for each group, and statistical analysis was performed between groups. The rats were kept in an atmosphere of 20-26°C and 40-70% RH. Under these collection conditions, it can be said that natural drying of the feces between excretion and collection does not significantly affect the measured fecal (wet) weight or fecal properties.

[0054] [Table 7]

[0055] The results are shown in Table 8. In this test, there was almost no difference in the total dry weight of feces collected over 24 hours between the groups. The percentage of normal feces (%) shown in Table 8 is the highest value among the percentages of normal feces calculated each time feces were collected.

[0056] In the control group, a decrease in the proportion of animals with normal stool and an increase in the water content of the stool were observed compared to the untreated group, confirming that castor oil administration induced diarrhea. In the itopride-only group, the proportion of animals with normal stool was similar to that in the control group, but the water content in the stool increased, indicating a tendency for diarrhea to worsen. In the sucralfate-only group, the proportion of animals with normal stool and the water content in the sucralfate-only group were similar to the control group, and no effect on preventing or improving diarrhea was observed.

[0057] In contrast, the itopride-sucralfate combination group showed a higher percentage of individuals with normal stools and a clear decrease in fecal water content compared to the control group. This indicates that the combined use of itopride hydrochloride and sucralfate hydrate is highly effective in preventing or improving diarrhea.

[0058] [Table 8]

[0059] Formulation example Tablets having the compositions shown in Table 9 and granules having the compositions shown in Table 10 were prepared. Table 9 shows the composition of each tablet. When three tablets of each composition shown in Formulation Examples 1 to 3, 5 to 6, and 8 to 12 in Table 9 were taken daily, and six tablets of each composition shown in Formulation Examples 4 and 7 were taken daily, respectively, a preventive or ameliorative effect on irregular bowel movements was observed. Table 10 also shows the composition of granules per packet. When three packets of each granule of the composition shown in Table 10 were taken daily, a preventive or ameliorative effect on irregular bowel movements was observed.

[0060] [Table 9]

[0061] [Table 10]

Claims

1. (A) itopride and / or a salt thereof, and (B) at least one selected from the group consisting of aldioxa, glutamine, teprenone, and sucralfate hydrate An oral pharmaceutical composition comprising:

2. 2. The pharmaceutical composition for internal use according to claim 1, wherein component (B) is aldioxa and contains 0.1 to 5 parts by weight of aldioxa per 1 part by weight of itopride and / or a salt thereof.

3. 2. The pharmaceutical composition for internal use according to claim 1, wherein the component (B) is glutamine, and the composition contains 0.1 to 20 parts by weight of glutamine per 1 part by weight of itopride and / or a salt thereof.

4. 2. The pharmaceutical composition for oral administration according to claim 1, wherein the component (B) is teprenone and contains 0.1 to 3 parts by weight of teprenone per 1 part by weight of itopride and / or a salt thereof.

5. 2. The pharmaceutical composition for oral administration according to claim 1, wherein said component (B) is sucralfate hydrate, and the composition contains 0.25 to 25 parts by weight of sucralfate hydrate per part by weight of itopride and / or a salt thereof.

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