ORAL PHARMACEUTICAL COMPOSITION.

Abstract

A means is provided that is capable of preventing the initial excessive release of an active ingredient and that allows the sustained release of a pharmaceutically active amount of the active ingredient over a long period of time.

Description

ORAL PHARMACEUTICAL COMPOSITION Field of Invention This description relates to an oral pharmaceutical composition containing a salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one (more preferably a controlled-release oral pharmaceutical composition), and the like. The contents of all documents mentioned in this specification are incorporated herein by reference. Background of the Invention 7-[4-(4-Benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-1Hquinolin-2-one (hereafter also referred to as compound (I) or brexpiprazole), or a salt thereof, has partial agonist action at the dopamine D2 receptor, antagonist action at the serotonin 5-HT2A receptor, and antagonist action at the adrenergic "i" receptor. In addition to these actions, compound (I) or a salt thereof has serotonin reuptake inhibitory action (or serotonin reuptake inhibitory action), and is known to have a broad therapeutic spectrum for diseases of the central nervous system (CNS) (particularly schizophrenia) (Patent Literature (PTL) 1). List of appointments Patent literature PTL 1: JP2006-316052A MA / a / zuzz / uun zoo Ref. 330917 Summary of the Invention Technical problem In the treatment of CNS disorders, such as schizophrenia, it is generally important that the drug be present in the plasma at a therapeutically effective concentration for an extended period. Therefore, an oral pharmaceutical composition that can be administered infrequently is useful because it improves patient compliance and reduces the relapse rate during treatment. To obtain an oral pharmaceutical composition that can be administered infrequently, one might consider producing a composition containing a high dose of an active ingredient. However, in order to maintain an effective blood concentration for treatment, the active ingredient must be continuously released from the composition at an appropriate rate while avoiding excessive release after administration due to factors related to the living body. In the treatment of schizophrenia using compound (I) or a salt thereof, once-daily oral administration is currently recommended. However, once-daily oral administration places an undue burden on many patients requiring long-term management. Therefore, there has been a demand for an orally administerable pharmaceutical composition suitable for less frequent administration than once daily. Solution to the problem The present inventors carried out extensive research and found, for the first time, a composition containing a salt of compound (I) as an orally administerable pharmaceutical composition suitable for administration less frequently than once a day. This description includes, for example, the subjects described in the following articles. Point 1. A controlled-release oral solid pharmaceutical composition comprising a 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one salt as the active ingredient, and further comprising an additive containing an ion in common with the salt. Point 2. The composition according to point 1, wherein the active ingredient is a fumaric acid salt, a phosphoric acid salt, a hydrochloric acid salt, a sulfuric acid salt, a citric acid salt or a tartaric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-lyl)butoxy]-1H-quinolin-2-one. Point 3. The composition according to point 1, wherein the active ingredient is a fumaric acid salt of 7—[4—(4—benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one, and the additive containing an ion in common with the salt is at least one member selected from the group consisting of fumaric acid, monosodium fumarate, and disodium fumarate. Point 4. 4. The composition according to any of points 1 to 3, further comprising a water-soluble cellulose-based polymer. Point 5. The composition according to point 4, wherein the water-soluble cellulose-based polymer is at least one member selected from the group consisting of hydroxypropyl methylcellulose, hydroxypropyl cellulose, and methylcellulose. Point 6. The composition according to any of Points 1 to 5, which is an osmotic pump composition. Point 7. The composition according to point 6, wherein the composition of the osmotic pump comprises a drug layer comprising a water-soluble polymer based on ML / a / zuzz / uui roo cellulose. Point 8. The composition according to point 7, where the water-soluble cellulose-based polymer is hydroxypropylmethylcellulose. Point 9. The composition in accordance with any of Points 1 to 5, which is a sustained-release hydrogel composition. Point 10. The composition according to Point 9 comprising an enteric coating. Item 11. The composition in accordance with any of Points 1 to 10, containing from 5 mg to 70 mg of the active ingredient in terms of weight of 7-[4-(4-benzo[b]tlofen-4-yl-piperazin-l yl)butoxy]-lH-quinolin-2-one. Item 12. The composition in accordance with any of Points 1 to 11, wherein a blood concentration level of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-1Hquinolin-2-one is maintained at a steady state when administered orally to a human in the range of 15 ng / mL to 400 ng / mL for 1 week. Item 13. The composition according to any of Points 1 MA / a / zuzz / uui roo a 12, which is for use in the administration of a 7[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin2-one salt once a week at a dose of 5 mg to 60 mg depending on the weight of the free base. Item 14. The composition in accordance with any of Points 1 to 13, for use in preventing or treating a disease of the central nervous system (CNS). Point 15. The composition according to point 14, wherein the composition is for preventing or treating a selected CNS disease from the group consisting of schizophrenia; treatment-resistant, refractory, or chronic schizophrenia; emotional disorder; psychotic disorder; mood disorder; bipolar disorder; depression; endogenous depression; major depression; treatment-resistant melancholic depression; dysthymic disorder; cyclothymic disorder; anxiety disorder; somatoform disorder; factitious disorder; dissociative disorder; sexual disorder; eating disorder; sleep disorder; adjustment disorder; substance-related disorder; anhedonia; delirium; cognitive impairment; cognitive impairment associated with neurodegenerative diseases; cognitive impairment caused by neurodegenerative diseases; cognitive impairment of schizophrenia; cognitive impairment caused by treatment-resistant, refractory, or chronic schizophrenia; vomiting;motion sickness; obesity; migraine; pain; mental disorders; intellectual disability; autism spectrum disorder; Tourette syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia; and borderline personality disorder. Point Al. A pharmaceutical formulation, which is an oral solid formulation of an osmotic pump-controlled release system having a structure such that a core formulation comprising a laminate of a drug layer and a pusher layer is coated with a semipermeable membrane, the drug layer comprising a salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one. Point A-2. The pharmaceutical formulation according to point Al, wherein the salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one is a fumaric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-1Hquinolin-2-one. Point A-3. The pharmaceutical formulation according to point A1 or A-2, wherein the drug layer comprises an additive containing an ion in common with the salt of 7-[4-(4-benzo[b]thiophen] 4-yl-piperazine-l-yl)butoxy]-lH-quinolin-2-one. (For example, in the case of Point A-2 where the salt of 7-(4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one is a fumaric acid salt, examples of additives containing an ion in common with the salt include fumaric acid, monosodium fumarate, disodium fumarate, and the like). In this case, the ion in common with the salt is the fumarate ion.) Point Bl. The composition according to any of points 1 to 15, wherein the composition comprises a 7-(4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one salt as the active ingredient, and releases the active ingredient in a sustained manner for a period of 5 to 30 hours. Point B-2. The composition according to any of points 6 to 8, wherein the composition of the osmotic pump comprises a thrust layer containing at least one osmotic agent that is an inorganic salt or a saccharide and / or a sugar alcohol. Point B-3. The composition according to point B-2, where the osmotic agent is sodium acid carbonate. Point B-4. The composition in accordance with any of Points 6 to 8 and Points B-2 to B-3, where the pump composition MA / a / zuzz / uun osmotic zoo comprises a drug layer comprising light anhydrous silicic acid. Point B-5. The composition according to Point 1 or 3, which is an osmotic pump composition comprising a drug layer and a pusher layer, wherein the drug layer comprises a 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-lyl)butoxy]-1H-quinolin-2-one salt, an additive containing an ion in common with the salt, and a water-soluble cellulose-based polymer, and the pusher layer comprises at least one osmotic agent which is an inorganic salt, or a saccharide and / or a sugar alcohol. Point B-6. The composition according to any of Points 6 to 8 and Points B-2 to B-4, comprising a core formulation comprising a drug layer and a booster layer, wherein the drug layer comprises 5 to 200 mg of a 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-1Hquinolin-2-one salt on a weight basis of the free base, to 50% by mass of an additive containing an ion in common with the salt, based on the weight of the drug layer, to 94% by mass of a hydrophilic polymer, based on the weight of the drug layer, 0.1 to 5% by mass of a lubricant, based on the weight of the drug layer, and 0.1 to 5% by mass of a fluidifier, based on the weight of the drug layer, the booster layer comprising 90% by mass of a highly swellable polymer, based on the weight of the booster layer, to 50% by mass of an osmotic agent, based on the weight of the booster layer, 0.1 to 5% by mass of a lubricant, based on the weight of the thrust layer, and 0.1 to 2% by weight of a pigment, based on the weight of the push layer, the core formulation comprises 5 to 25 parts by mass of a semipermeable membrane and 1 to 15 parts by mass of a water-soluble polymeric membrane, based on 100 parts by mass of the core formulation, the semipermeable membrane comprises 70 to 100% by mass of a cellulose-based polymer and 0.01 to 30% by mass of a water-soluble flow-regulating agent, based on the weight of the semipermeable membrane, and the composition optionally comprises a color coating layer. Point B-7. The composition according to point 9 or 10, which is a composition comprising a tablet core, wherein the composition comprises 200 mg of a 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-l-yl)butoxy]-lH-quinolin-2-one salt on a weight basis of the free base, 50% by mass of an additive containing an ion in common with the salt, based on the weight of the tablet core, 90% by mass of a sustained-release base material, based on the weight of the tablet core, and 0.1 to 5% by mass of a lubricant, based on the weight of the tablet core, and further comprises 1 to 40 parts by mass of an enteric coating per 100 parts by mass of the tablet core. Point B-8. A controlled-release oral solid pharmaceutical composition comprising a 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one salt as the active ingredient, and maintaining a steady-state blood concentration of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one in the range of 15 ng / mL to 400 ng / mL for 1 week, when administered orally to a human. Point B-9. A controlled-release oral solid pharmaceutical composition comprising a 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one salt as an ingredient MA / a / zuzz / uun active zoo, administering the active ingredient at a dose of 5 to 60 mg once a week in terms of 7-(4-(4benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one. Advantageous effects of the invention According to the present description, a means can be provided that prevents the initial excessive release of an active ingredient (i.e., a salt of compound (I)) from a pharmaceutical composition, even when the composition is administered at a high dose, and that allows the sustained release of a therapeutically effective amount of the active ingredient over a long period of time. This can maintain a therapeutically effective blood concentration of the active ingredient for an extended period (approximately two weeks at most). Therefore, according to the present description, a disease (e.g., schizophrenia) that responds to a salt of compound (I) can be treated by less frequent administration than conventional methods, and the present description is thus effective in improving medication adherence in patients. Examples of disease that responds to compound (I) or a salt thereof include various CNS diseases, such as schizophrenia; treatment-resistant, refractory, or chronic schizophrenia; emotional disorder; psychotic disorder; mood disorder; bipolar disorder (e.g., bipolar I disorder and bipolar II disorder); depression; endogenous depression; major depression; melancholic and treatment-resistant depression; dysthymic disorder; cyclothymic disorder; anxiety disorder (e.g., panic attack, panic disorder, agoraphobia, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and acute stress disorder); somatoform disorder (e.g., hysteria, somatization disorder, conversion disorder, pain disorder, and hypochondria); factitious disorder; dissociative disorder;sexual disorder (e.g., sexual dysfunction, libido disorder, sexual arousal disorder, and erectile dysfunction); eating disorder (e.g., anorexia nervosa and bulimia nervosa); sleep disorder; adjustment disorder; substance-related disorder (e.g., alcohol abuse, alcohol intoxication and drug addiction, amphetamine addiction, and narcotics); anhedonia (e.g., loss of pleasure, anhedonia, iatrogenic anhedonia, anhedonia of psychic or mental origin, anhedonia associated with depression, anhedonia associated with schizophrenia); delirium; cognitive impairment; cognitive impairment associated with Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases; cognitive impairment caused by Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases; cognitive impairment in schizophrenia;Cognitive impairment caused by treatment-resistant, refractory, or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; intellectual disability; autistic disorder (autism); Tourette syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia (e.g., agitation associated with Alzheimer's disease); and borderline personality disorder. Brief Description of the Figures Figure 1 shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 11 to 1-5 (eluate pH: approximately 4.3). Fig. 1b shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 11 to 1-5 (eluate pH: approximately 7). Fig. 2 shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples ΣI a 2-4 (eluate pH: approximately 7). Fig. 3 shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 31 to 3-9 (eluate pH: approximately 4.3). Fig. 4a shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 41 to 4-3 (eluate pH: approximately 7, with a surfactant). Fig. 4b shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 41 to 4-3 (eluate pH: approximately 7). Fig. 5a shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 51 to 5-3 (eluate pH: approximately 4.3). Fig. 5b shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 51 to 5-3 (eluate pH: approximately 7). Fig. 6a shows the results of a dissolution test of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 61 to 6-4 (eluate pH: approximately 7, with a surfactant). Figure 6b shows the results of a test of MA / a / zuzz / uun zoo dissolution of oral pharmaceutical compositions (osmotic pump formulations) obtained in Examples 61 to 6-4 (pH of eluate: approximately 7). Fig. 7 shows the results of the dissolution test of oral pharmaceutical compositions (osmotic pump formulations) comprising various salts of compound (I) and various additives. Fig. 8a shows the results of the dissolution test of oral pharmaceutical compositions (osmotic pump formulations) comprising various salts of compound (I) and various additives. Fig. 8b shows the results of the dissolution test of oral pharmaceutical compositions (osmotic pump formulations) comprising various salts of compound (I) and various additives. Fig. 8c shows the dissolution test results of oral pharmaceutical compositions (osmotic pump formulations) comprising various salts of compound (I) and various additives. Fig. 8d shows the results of the dissolution test of oral pharmaceutical compositions (osmotic pump formulations) comprising various salts of compound (I) and various additives. Fig. 8e shows the results of the dissolution test of oral pharmaceutical compositions (osmotic pump formulations) comprising various salts of compound (I) and various additives. Fig. 8f shows the results of the dissolution test of oral pharmaceutical compositions (osmotic pump formulations) comprising various salts of compound (I) and various additives. Fig. 8g shows the dissolution test results of oral pharmaceutical compositions (osmotic pump formulations) comprising various salts of compound (I) and various additives. Fig. 9a shows the results of dissolution tests of oral pharmaceutical compositions (hydrogel matrix tablets) comprising various salts of compound (I) and various additives. Fig. 9b shows the results of dissolution tests of oral pharmaceutical compositions (hydrogel matrix tablets) comprising various salts of compound (I) and various additives. Fig. 10a shows the results of dissolution tests of oral pharmaceutical compositions (hydrogel matrix tablets) comprising various salts of compound (I) and various additives. Fig. 10b shows the results of dissolution tests of oral pharmaceutical compositions (hydrogel matrix tablets) comprising various salts of compound (I) and various additives. Fig. lia shows the infrared absorption spectrum of a fumaric acid salt of compound (I). Fig. 11b shows the powder X-ray diffraction pattern of a fumaric acid salt of compound (I). Fig. 11c shows the infrared absorption spectrum of a citric acid salt of compound (I). Fig. lid shows the powder X-ray diffraction pattern of a citric acid salt of compound (I). Fig. lie shows the infrared absorption spectrum of a tartaric acid salt of compound (I). Fig. llf shows the powder X-ray diffraction pattern of a tartaric acid salt of compound (I). Fig. llg shows the infrared absorption spectrum of a phosphoric acid salt of compound (I). Fig. 11h shows the powder X-ray diffraction pattern of a phosphoric acid salt of compound (I). Fig. lli shows the infrared absorption spectrum of a hydrochloric acid salt of compound (I). Fig. 11j shows the powder X-ray diffraction pattern of a hydrochloric acid salt of compound (I). Fig. llk shows the infrared absorption spectrum of a sulfuric acid salt of compound (I). Fig. 111 shows the powder X-ray diffraction pattern of a sulfuric acid salt of compound (I). Figure 12 shows an example of an osmotic pump composition, which is a type of controlled-release oral pharmaceutical composition. Detailed Description of the Invention The present description preferably includes an oral pharmaceutical composition, a method for producing the oral pharmaceutical composition, and the like. However, the description is not limited to these, and includes everything described in the present invention that can be recognized by a person skilled in the art. The oral pharmaceutical composition according to the present description includes a salt of compound (I). This oral pharmaceutical composition may be referred to as the oral pharmaceutical composition according to the present description. Compound (I) refers to a compound represented by the following formula (I). Compound (I) or a salt thereof may be produced by the method described in JP2006-316052A (which is incorporated herein in its entirety by reference), or a method similar to it. MA / a / zuzz / uun zoo The salt of compound (I) is not particularly restricted, provided it is a pharmaceutically acceptable salt. Examples include various metal salts, salts of inorganic bases, salts of organic bases, salts of inorganic acids, salts of organic acids, and the like. Examples of metal salts include salts of alkali metals (e.g., sodium salts and potassium salts), salts of alkaline earth metals (e.g., calcium salts and magnesium salts), and the like.Examples of salts of inorganic bases include ammonium salts and salts of alkali metal carbonates (e.g., lithium carbonate, potassium carbonate, sodium carbonate, and cesium carbonate), hydrogen carbonates of alkali metals (e.g., lithium hydrogen carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate), hydroxides of alkali metals (e.g., lithium hydroxide, sodium hydroxide, potassium hydroxide, and cesium hydroxide), and similar inorganic bases. Examples of salts of organic bases include salts of (lower) trialalkylamines (e.g., trimethylamine, triethylamine, and ethyldiisopropylamine), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-alkyl(lower)-morpholines (e.g., N-methylmorpholine), 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO). And similar organic bases. Examples of salts of inorganic acids include salts of hydrochloric acid, salts of hydrobromic acid, salts of hydroiodic acid, salts of sulfuric acid, salts of nitric acid, salts of phosphoric acid, and the like. Examples of salts of organic acids include salts of formic acid, salts of acetic acid, salts of propionic acid, salts of oxalic acid, salts of malonic acid, salts of succinic acid, salts of fumaric acid, salts of maleic acid, salts of lactic acid, salts of malic acid, salts of citric acid, salts of tartaric acid, salts of carbonic acid, salts of picric acid, salts of methanesulfonic acid, salts of ethanesulfonic acid, salts of p-toluenesulfonic acid, salts of glutamic acid, salts of benzoic acid, and the like. Among these, the preferred salts are hydrochloric acid salts, sulfuric acid salts, fumaric acid salts, phosphoric acid salts, citric acid salts, and tartaric acid salts. Examples of salts of compound (I) include anhydrides, solvates with a solvent (e.g., hydrate, methanolate, ethanolate, and acetonitrilate), various crystalline forms of anhydrides and solvates, and mixtures thereof. Compound (I) or a salt thereof also includes isomers such as geometric isomers, stereoisomers, and optical isomers. The salt of compound (I) may be a pharmaceutically acceptable cocrystal salt. The term cocrystal or cocrystalline salt, as used herein, means a crystalline material composed of two or more unique solids at room temperature that differ in physical characteristics (such as structure, melting point, and heat of fusion). Cocrystals and cocrystal salts may be produced by known cocrystallization methods. The oral pharmaceutical composition described herein is designed as a dosage form suitable for releasing a salt of compound (I) at a uniform rate over a prolonged period of time; and preferably designed as a dosage form suitable for maintaining a constant dissolution concentration, even in the lower gastrointestinal tract. More specifically, the oral pharmaceutical composition is designed as a controlled-release oral pharmaceutical composition. The dissolution rate and sustained release time of a salt of compound (1) of the oral pharmaceutical composition can be obtained by measuring the dissolution rate and sustained release time of the salt of compound (I) according to the second method (paddle method) of the Japanese Pharmacopoeia dissolution test using, as a test solution, a buffer solution of pH 5.0 or less that achieves the sedimentation conditions (specifically, a 0.05 mol / L acetate buffer solution (pH 4.3, acetic acid, sodium acetate)). The dissolution rate refers to the ratio of the dissolved salt of compound (I) to the total amount of compound (I) salt contained in the oral pharmaceutical composition. Therefore, the dissolution rate can be paraphrased as the proportion of compound (I) dissolved relative to the total amount of compound (I) contained in the oral pharmaceutical composition. The sustained release time is the time from the start of the dissolution test measurement until the final dissolution rate is reached. The final dissolution rate is the rate of dissolution when a plateau is reached in the dissolution test, and the final amount of dissolution is the amount of dissolution (elution) when the final dissolution rate is reached in the dissolution test.In the dissolution test, when the dissolution rate at a certain time (the reference time point) is compared with the dissolution rate two hours after the reference time point, and if the dissolution rate two hours after the reference time point falls within the range of the dissolution rate at the reference time point i ± 1% (preferably, when the dissolution rate more than two hours after the reference time point is compared with the dissolution rate at a certain time point (the reference time point) and if the dissolution rate more than two hours after the reference point falls within the range of the dissolution rate at the reference point ± 1%), a plateau can be considered to have been reached at the reference time point that is the shortest in time since the start of the test.However, the dissolution rate at the reference time point must be greater than 20% (in other words, when the dissolution rate does not exceed 20%, it is not considered a plateau). The sustained-release time is preferably 5 hours or more. The sustained-release time is preferably 30 hours or less. More preferably, the sustained-release time is 5 to 30 hours. The upper or lower limit of the sustained-release time range is, for example, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 hours. The sustained-release time is, for example, even more preferably 10 to 24 hours, and even more preferably 15 to 24 hours. The final dissolution amount of the oral pharmaceutical composition according to the present description is preferably 80% by mass or more of the total amount of the salt of compound (I) contained in the oral pharmaceutical composition (typically, the oral pharmaceutical formulation). More preferably, the final dissolution amount is 81, 82, 83, 84, 84, 85, 85, 86, 87, 88, 89, or 90% by mass or more. It is possible to assess whether a constant dissolution concentration is maintained in the lower part of the gastrointestinal tract by measuring the supersaturated dissolution concentration profile of the salt of compound (I) per dissolution time using as test liquid a phosphate buffer solution of approximately pH 7, which simulates the lower part of the gastrointestinal tract, according to the second method (paddle method) of the Japanese Pharmacopoeia dissolution test. To achieve sustained release, an increase in the initial dissolution of the salt of compound (I) from the composition can be achieved immediately after the start of the dissolution test, or a certain amount of time (e.g., 1 to 3 hours) after the start of the measurement. However, it is not desirable for more than 5 hours to elapse before the amount of dissolution is 5% by mass or more of the final amount of dissolution. The supersaturated dissolution profile can be evaluated by quantifying, over time, the concentration of the drug temporarily dissolved to a solubility level higher than that of compound (I) in the paddle method dissolution test using the aforementioned phosphate buffer solution of approximately pH 7 (test fluid simulating the lower gastrointestinal tract). A preferred supersaturated dissolution profile is one that reaches a peak dissolution rate at a time point between 4 and 18 hours after the start of the dissolution test. Furthermore, the peak is preferably 1 or 1.5 pg / mL or higher, more preferably 2, 2.5, or 3 pg / mL or higher, and even more preferably 3.5, 4, 4.5, 5, 5.5, or 6 pg / mL or higher, in terms of compound (I) (free base).A higher supersaturated concentration contributes more to absorption in the lower gastrointestinal tract and is therefore expected to increase bioavailability (BA) and reduce peak-to-valley ratio (PTF). Such an improvement in BA or reduction in PTF facilitates adjustment to the target pharmacokinetic (PK) range. The method by which a salt of compound (I) is released from the oral pharmaceutical composition at a uniform rate over a long period is not particularly limited and can be achieved using various techniques known in the field of sustained-release formulations. Preferred sustained-release approaches include those that utilize, for example, a diffusion-controlled composition, a dissolution-controlled composition, or an osmotic pump-controlled composition. Among these, the most preferable sustained-release approaches are, for example, an osmotic pump-controlled composition (especially an osmotic controlled-release oral delivery system: OROS) and a hydrogel sustained-release composition.An oral pharmaceutical composition of this type is preferably a solid oral pharmaceutical composition (in particular, a solid formulation) from the point of view of its ease of handling. The oral pharmaceutical composition described herein preferably further contains an additive that shares an ion with a salt of compound (I). For example, when the salt of compound (I) is a fumaric acid salt, examples of additives sharing an ion with the salt include fumaric acid, monosodium fumarate, disodium fumarate, and the like. In this case, the ion shared with the salt is a fumarate ion. A person skilled in the art could determine which ion is shared with the salt of compound (I) based on the type of salt of compound (I) used and employ an additive containing that ion. Examples of such additives include, but are not limited to, inorganic salts, inorganic acids, organic salts, and organic acids, each of which shares an ion with the salt of compound (I).Examples of inorganic salts include sodium chloride, sodium bicarbonate, sodium carbonate, sodium phosphate (trisodium phosphate), potassium phosphate (tripotassium phosphate), sodium acid phosphate (sodium dihydrogen phosphate, disodium acid phosphate), potassium acid phosphate (potassium dihydrogen phosphate, dipotassium acid phosphate), potassium chloride, lithium chloride, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, sodium sulfite, potassium sulfite, lithium sulfate, potassium acid phosphate, and similar compounds. Examples of inorganic acids include acids that form the inorganic salts listed above.Examples of organic salts include sodium fumarate (disodium fumarate), sodium hydrogen fumarate (monosodium fumarate), sodium hydrogen tartrate, potassium hydrogen tartrate, sodium tartrate, potassium sodium tartrate, sodium malate (disodium malate), sodium hydrogen succinate, sodium succinate (disodium malate), sodium hydrogen maleate, sodium maleate (disodium maleate), sodium hydrogen citrate (sodium dihydrogen citrate, disodium hydrogen citrate), sodium citrate (trisodium citrate), and similar compounds. Examples of organic acids include acids that form the organic salts mentioned above. These can be anhydrides or solvates (such as hydrates). The oral pharmaceutical composition according to the present description preferably contains a polymer MA / a / zuzz / uun water-soluble cellulose-based polymer. The water-soluble cellulose-based polymer is preferably contained in a drug-containing composition. The preferred water-soluble cellulose-based polymer is, for example, a water-soluble cellulose-based polymer known in the pharmaceutical field. For example, a water-soluble cellulose-based polymer having a structure in which some of the hydrogen atoms of the OH groups of cellulose are replaced with methyl and / or hydroxypropyl groups is preferred. Specific examples of preferred water-soluble cellulose-based polymers include hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, and the like. Water-soluble cellulose-based polymers may be used alone or in a combination of two or more. The present description is further detailed below with reference to an osmotic pump controlled-release composition, which is a preferred oral solid pharmaceutical composition. The osmotic pump controlled-release composition in formulation form may be referred to as an osmotic pump formulation. The composition of an osmotic pump typically consists of a structure in which a drug and a substance that generates osmotic pressure as needed (an osmotic agent), such as a salt, are surrounded by a semipermeable membrane. The semipermeable membrane has pores through which the drug can be released. A fluid (e.g., water) enters through the semipermeable membrane according to the osmotic pressure and dissolves the drug and the osmotic agent in it. This increases the osmotic pressure gradient across the semipermeable membrane, causing more fluid to flow into it, further dissolving and releasing the drug.The composition of the osmotic pump is advantageous because, since the rate of drug release does not depend on the pH of the environment, even if the composition passes through the gastrointestinal tract and encounters a significantly different pH environment, the composition can sustainably release the drug at a constant rate according to the osmotic pressure for a long period of time. For one embodiment of an oral pharmaceutical composition described herein, which is an osmotic pump composition, an explanation is provided below with reference to the figures. In Fig. 12, the osmotic pump composition 1 (hereafter referred to simply as formulation 1) includes a wall 2 surrounding an internal compartment 5 in which a composition containing a salt of compound (I) is present. The wall 2 has at least one drug release port 3 communicating the external environment with the internal compartment. The internal compartment 5 contains a two-layer compressed core comprising a drug layer 6 and a thrust layer 7. The drug release port 3 is preferably provided in the wall 2 to communicate the internal compartment 5 on the side of the drug layer 6 with the external environment. One or more drug release ports 3 may be provided.For example, the formulation may have two or three drug release ports 3. Wall 2 is a semipermeable membrane through which water and external liquids penetrate, but through which drugs, osmotic agents, and the like do not permeate. The drug layer 6 comprises a salt of compound (I) in the form of a mixture with one or more additives. The booster layer 7 does not comprise any salt of compound (I) and comprises an osmotic agent and a highly swellable polymer. The osmotic agent refers to an ingredient that is water-soluble and raises the concentration of an electrolyte in a pharmaceutical formulation, such as an inorganic salt and a saccharide and / or a sugar alcohol. The highly swellable polymer means a polymer that absorbs a liquid and swells (preferably a polymer with a relatively high molecular weight). The highly swellable polymer absorbs a liquid and swells, thereby releasing a salt of compound (I) through the release port 3.The drug layer 6 and the push layer 7 may also contain additives, such as cellulose-based polymers like cellulose ester, cellulose ether, and cellulose ester-ether. Specific examples include cellulose acylate, cellulose diacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, cellulose triacetate, mono-, di-, and tricellulose alkanylate, mono-, di-, and tri-kelinelate, mono-, di-, and tri-allylate, and similar compounds. Cellulose acetate is preferred among these. The semipermeable membrane can be prepared from the polymer using a known method. In addition to the above, other examples of semipermeable polymers for forming a semipermeable membrane of the osmotic pump composition include the following: cellulose dimethyl acetate acetaldehyde; cellulose ethyl acetate carbamate; cellulose methyl acetate carbamate; cellulose dimethylaminoacetate; semipermeable polyurethane; semipermeable sulfonated polystyrene; selectively semipermeable crosslinked polymers formed by anion and cation coprecipitation, as described in U.S. Patent Nos. 3,173,876, 3,276,586, 3,541,005, 3,541,006, and 3,546,142; semipermeable polymers, as described in U.S. Patent No.3,133,132; semipermeable polystyrene derivatives; semipermeable poly(sodium styrene sulfonate); semipermeable poly(vinyltrimethylammonium chloride); and a semipermeable polymer exhibiting a liquid permeability of 10-5 to 10-2 (cc ml / cm hr atm) in terms of a hydrostatic pressure difference or an osmotic pressure difference per atmosphere when permeabilizing through a semipermeable wall. Such polymers exemplified for use in forming the semipermeable membrane can be used alone or in a combination of two or more. The semipermeable membrane may contain a flow-regulating agent. A flow-regulating agent is a substance added to help regulate the permeability of the fluid or the volume of fluid passing through the semipermeable membrane. A flow-regulating agent may be either a substance that increases flow (hereafter referred to as a flow-enhancing agent) or a substance that decreases flow (hereafter referred to as a flow-reducing agent). A flow-enhancing agent is essentially hydrophilic, while a flow-reducing agent is essentially hydrophobic. Examples of flow-regulating agents include polyhydric alcohols, polyalkylene glycols, polyalkylenediols, alkylene glycol polyesters, and the like. Examples of representative flow-enhancing agents include polyethylene glycols (which have an average molecular weight of 190 to 9000, such as polyethylene glycol). 300, 400, 600, 1500, 3000, 3350, 4000, 6000 or 8000); low molecular weight glycols, such as polypropylene glycol, polybutylene glycol and polyamylene glycol; polyalkylenediols, such as poly(1,3-propanediol), poly(1,4-butanediol) and poly(1,6-hexanediol); fatty acids, such as 1,3-butylene glycol, 1,4-pentamethylene glycol and 1,4-hexamethylene glycol; alkylene triols, such as glycerin, 1,2,3-butanetriol, 1,2,4-hexanetriol and 1,3,6-hexanetriol; Esters, such as ethylene glycol dipropionate, ethylene glycol butyrate, butylene glycol dipropionate, and glycerol acetate esters. Preferred flow-enhancing agents include polyoxyalkylene derivatives of propylene glycol difunctional block copolymer known as Pluronics (BASF), and similar products. Typical flow-reducing agents include alkyl- or alkoxy-substituted phthalates, or phthalates with both alkyl and alkoxy groups, such as diethyl phthalate, dimethoxyethyl phthalate, dimethyl phthalate, and [di(2-ethylhexyl) phthalate]; aryl phthalates such as triphenyl phthalate and butylbenzyl phthalate; insoluble salts such as calcium sulfate, barium sulfate, and calcium phosphate; insoluble oxides such as titanium oxide; polymers in the form of, for example, a powder or granules, such as polystyrene, polymethyl methacrylate, polycarbonate, and polysulfone; esters such as citric acid esters esterified with chain-linked alkyl groups MA / a / zuzz / uun long zoo; inert and water-impermeable fillings; resins compatible with cellulose-based wall-forming materials; and the like. Such exemplified flow regulating agents can be used alone or in a combination of two or more. The semipermeable membrane may contain other substances, for example, to impart flexibility and elongation properties, to make the membrane less brittle, or to give it tear resistance. Examples of materials appropriately added for this purpose include plasticizers. Specific examples include phthalate plasticizers such as dibenzyl phthalate, dihexyl phthalate, octyl butyl phthalate, Ce-Cu linear chain phthalates, diisononyl phthalate, diisodecyl phthalate, and the like. Other examples of plasticizers include non-phthalates such as triacetin, dioctyl azelate, epoxidized phthalate, triisoctyl trimellitate, triisononyl trimellitate, sucrose acetate isobutyrate, and epoxidized soybean oil. When a plasticizer such as those mentioned above is present in the semipermeable membrane, the amount of plasticizer is approximately 0.0.1 to 30% by mass or more, based on the total amount of all components of the semipermeable membrane. The pusher layer contains a composition for pushing a salt of compound (I) and is in a layered arrangement in contact with the drug layer, for example, as shown in Fig. 12. As described above, the pusher layer comprises a highly swellable polymer that absorbs an aqueous liquid or biological fluid and swells to extrude a salt of compound (I) through the release port of the formulation. The highly swellable polymer is preferably a hydrophilic swellable polymer that interacts with water or an aqueous biological fluid and swells or expands significantly, typically exhibiting a volume increase of 2 to 50 times. The highly swellable polymer may be crosslinked or non-crosslinked. In a preferred embodiment, the polymer is crosslinked, preferably at least to create an extended polymer network that is too large to escape from the formulation.Therefore, in a preferred embodiment, the swellable composition is retained in the formulation throughout its effective shelf life. Examples of highly swellable polymers include poly(alkylene oxide) having a number-average molecular weight of 10,000 to 15,000,000, such as polyethylene oxide, and poly(alkaline carboxymethylcellulose) having a number-average molecular weight of 500,000 to 3,500,000 (where the alkali is sodium, potassium, or lithium).Examples of highly swellable polymers also include polymers comprising hydrogel-forming polymers such as Carbopol (registered trademark), acidic carboxypolymers, polyallylsucrose crosslinked acrylic polymers (also known as carboxypolymethylene), and carboxyvinyl polymers having a molecular weight of 250,000 to 4,000,000; cyanamer polyacrylamides (registered trademark); crosslinked water-swellable indenemaleic anhydride polymers; Good-rite polyacrylic acid (registered trademark) having a molecular weight of 80,000 to 200,000; Aqua-Keeps (registered trademark), acrylate polymer polysaccharides composed of condensed glucose units, such as diester crosslinked polyglucan; and the like. Polymers that form hydrogels are described in U.S. Patents Nos. 3,865,108, 4,002,173, 4,207,893, etc. Such highly swellable polymers exemplified can be used alone or in a combination of two or more. The osmotic agent, sometimes also called the osmotic solute or osmotically effective agent, can be present in either the drug layer or the pusher layer. The osmotic agent (osmotic pressure regulator) is not particularly limited, as long as it presents an osmotic activity gradient across the semipermeable membrane. Examples include inorganic salts, inorganic acids, organic salts, organic acids, saccharides, sugar alcohols, and similar substances.Examples of inorganic salts include sodium chloride, sodium bicarbonate, sodium carbonate, sodium phosphate (trisodium phosphate), potassium phosphate (tripotassium phosphate), sodium acid phosphate (sodium dihydrogen phosphate, disodium acid phosphate), potassium acid phosphate (potassium dihydrogen phosphate, dipotassium acid phosphate), potassium chloride, lithium chloride, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, sodium sulfite, potassium sulfite, lithium sulfate, potassium acid phosphate, and similar compounds. Examples of inorganic acids include acids that form the inorganic salts listed above.Examples of organic salts include sodium fumarate (disodium fumarate), sodium hydrogen fumarate (monosodium fumarate), sodium hydrogen tartrate, potassium hydrogen tartrate, sodium tartrate, potassium sodium tartrate, sodium malate (disodium malate), sodium hydrogen succinate, sodium succinate (disodium malate), sodium hydrogen maleate, sodium maleate (disodium maleate), sodium hydrogen citrate (sodium dihydrogen citrate, disodium hydrogen citrate), sodium citrate (trisodium citrate), and the like. Examples of organic acids include acids that form the organic salts mentioned above. Examples of saccharides and sugar alcohols include mannitol, glucose, lactose, fructose, sucrose, sorbitol, xylitol, erythritol, and the like. These can be anhydrides or solvates (such as hydrates). These can be used alone or in a combination of two or more. The drug layer preferably contains an additive that shares a common ion with the salt of compound (I). For example, when the salt of compound (I) is a fumarate, examples of additives sharing a common ion include fumaric acid, monosodium fumarate, disodium fumarate, and similar compounds. In this case, the common ion is a fumarate ion. When the salt of compound (I) is a phosphate, examples of additives sharing a common ion include sodium phosphate (trisodium phosphate), potassium phosphate (tripotassium phosphate), sodium hydrogen phosphate (sodium dihydrogen phosphate, disodium hydrogen phosphate), potassium hydrogen phosphate (potassium dihydrogen phosphate, dipotassium hydrogen phosphate), and similar compounds. In this case, the common ion is a phosphate ion. When the salt of compound (I) is a hydrochloride, examples of additives containing a common ion include sodium chloride, potassium chloride, lithium chloride, magnesium chloride, and the like.In this case, the common ion is a chloride ion. When the salt of compound (I) is a sulfate, examples of additives containing a common ion include magnesium sulfate, potassium sulfate, sodium sulfate, lithium sulfate, and the like. In this case, the common ion is a sulfate ion. When the salt of compound (I) is a citrate, examples of additives containing a common ion include sodium hydrogen citrate (sodium dihydrogen citrate, disodium hydrogen citrate), sodium citrate (trisodium citrate), and the like. In this case, the common ion is a citrate ion. When the salt of compound (I) is a tartrate, examples of additives containing a common ion include sodium hydrogen tartrate, potassium hydrogen tartrate, sodium tartrate, sodium potassium tartrate, and the like. In this case, the common ion is a tartrate ion.An experienced person in the technique would understand, based on the type of salt of compound (I) used, which ion it shares with the salt of compound (I), and could use an additive containing that shared ion. Other examples of additives containing a shared ion with the salt of compound (I) that can be used are those described above. Examples of suitable solvents for use in manufacturing the osmotic pump composition or its components include inert aqueous or organic solvents that do not adversely affect the substances used in the composition. Examples of such solvents include at least one member selected from the group consisting of aqueous solvents, alcohols, ketones, esters, ethers, aliphatic hydrocarbons, halogenated solvents, cycloaliphatic, aromatic, or heterocyclic solvents, and mixtures thereof. Representative solvent examples include acetone, diacetone alcohol, methanol, ethanol, isopropanol, butyl alcohol, methyl acetate, ethyl acetate, isopropyl acetate, n-butyl acetate, methyl isobutyl ketone, methyl propyl ketone, n-hexane, n-heptane, ethylene glycol monoethyl ether, ethylene glycol monoethyl acetate, methylene dichloride, ethylene dichloride, propylene dichloride, carbon tetrachloride, nitroethane, nitropropane, tetrachloroethane, ethyl ether, isopropyl ether, cyclohexane, cyclooctane, benzene, toluene, naphtha, 1,4-dioxane, tetrahydrofuran, diglyme, water, an aqueous solvent containing an inorganic salt such as sodium chloride or calcium chloride, and mixtures thereof (such as a mixture of acetone and water, a mixture of acetone and methanol, a mixture of acetone and ethyl alcohol, a mixture of methylene dichloride and methanol, and a mixture of ethylene dichloride and methanol); and the like. The drug layer comprises a therapeutically effective amount of a salt of compound (I) and a carrier. The carrier may comprise a hydrophilic polymer. The hydrophilic polymer may provide, for example, hydrophilic polymer particles in the pharmaceutical composition that contribute to a uniform release rate and a controlled release pattern of the salt of compound (I). Examples of such polymers include poly(alkylene oxide) having a number-average molecular weight of 100,000 to 750,000, such as poly(ethylene oxide), poly(methylene oxide), poly(butylene oxide), and poly(hexylene oxide); and poly(carboxymethylcellulose) having a number-average molecular weight of 40,000 to 400,000, such as poly(alkaline carboxymethylcellulose), poly(sodium carboxymethylcellulose), poly(potassium carboxymethylcellulose), poly(lithium carboxymethylcellulose), and the like.The pharmaceutical composition may contain hydroxypropylalkylcellulose with a number-average molecular weight of 9,200 to 125,000, such as hydroxypropylethylcellulose, hydroxypropylmethylcellulose, hydroxypropylbutylcellulose, and hydroxypropylpentylcellulose, to improve the release properties of the composition; and poly(vinylpyrrolidone) with a number-average molecular weight of 7,000 to 75,000, to improve the flow properties of the composition. Among these polymers, poly(ethylene oxide) with a number-average molecular weight of 100,000 to 300,000 is preferred. Other carriers that may be present in the drug layer include carbohydrates that exhibit sufficient osmotic activity when used alone or with another osmotic agent. Carbohydrates include monosaccharides, disaccharides, and polysaccharides. Representative examples include saccharides such as maltodextrin (i.e., a glucose polymer produced by hydrolysis of corn starch), lactose, glucose, raffinose, sucrose, mannitol, and sorbitol. Preferred maltodextrins are those with a dextrose equivalence (DE) of 20 or less, preferably an DE of approximately 4 to approximately 20, and more preferably an DE of 9 to 20. A maltodextrin with an DE of 9 to 12 is preferred. Carbohydrates (preferably maltodextrin) are preferred because they can be used in the drug layer without adding another osmotic agent and impart long-term stability to the composition. The drug layer is, for example, a homogeneous, dry composition formed by compressing a vehicle and a drug. The drug layer can be formed from ground drug particles and an added polymer. Granulation can be carried out using established techniques such as granulation, spray drying, sieving, freeze-drying, grinding, polishing, fragmentation, and similar methods. Such granulation can be performed using devices such as a high-speed agitated granulator, an extrusion granulator, a fluidized bed granulator, and a roller compactor. The drug layer may contain one or more surfactants and one or more disintegrating agents. Examples of such surfactants include those with an HLB value of approximately 10 to 25 (specifically, polyethylene glycol 400 monostearate, polyoxyethylene-4-sorbitan monolaurate, polyoxyethylene-20-sorbitan monooleate, polyoxyethylene-20-sorbitan monopalmitate, polyoxyethylene-20 monolaurate, polyoxyethylene-40-stearate, sodium oleate, and the like). Examples of disintegrants include starches, clays, celluloses, algins, gums, crosslinked starches, polymers, and the like. Preferred disintegrants include corn starch, potato starch, croscarmellose, crospovidone, sodium starch glycolate, Veegum HV, methylcellulose, agar, bentonite, carboxymethylcellulose, alginic acid, guar gum, and the like. The drug layer may also contain light anhydrous silicic acid and similar substances. The semipermeable membrane can be formed on the surface of the two-layer compressed core, for example, by drum coating. More specifically, the semipermeable membrane can be formed by spraying the membrane-forming composition onto the surface of the two-layer compressed core, which comprises a drug layer and a propellant layer, while rotating on a drum. Coating techniques other than drum coating can also be used to coat the compressed core. For example, the semipermeable membrane can be formed using an air suspension process. This process involves suspending the compressed core in a stream of air and the semipermeable membrane-forming composition, and rotating it until a semipermeable membrane forms on the core. The air suspension process is well-suited for independently forming the semipermeable membrane.An air suspension technique of this type is known (e.g., U.S. Patent 2,799,241). It is also possible to use a Wurster air suspension cover (registered trademark) or an Aeromatic® air suspension cover (registered trademark). After coating with the semipermeable membrane, the membrane is dried, for example, in a forced-air oven or in an oven with controlled temperature and humidity, to remove the solvent. The drying conditions can be selected appropriately considering the available equipment, environmental conditions, solvents, coating materials, coating thickness, etc. The oral pharmaceutical composition described herein can be produced using a known formulation technique. For example, the oral pharmaceutical composition can be manufactured using techniques of MA / a / zuzz / uun zoo wet granulation or existing dry granulation techniques. More specifically, for example, in the case of wet granulation techniques, an organic solvent, such as an anhydrous denatured alcohol, is used as the granulation solution. A drug and an additive are mixed in a granulator and continuously granulated using the solvent to obtain granules. The granulation solution is added until a wet mixture is formed, and the wet mass mixture is passed through a pre-installed sieve in an oven tray. The mixture is then dried in a forced-air oven. Another granulation method is a layer-by-layer granulation operation of powder components in a fluidized bed granulator. After the powder components are dry-mixed in a granulator, the granulation liquid is sprayed onto the powder. The coated powder is then dried in a granulator.The dry granules obtained by these methods are graded in a granulator with a grinding mechanism. A lubricant, such as magnesium stearate, is then added, and the mixture is blended into granules using a blender (e.g., a V-type blender or a hand blender). The resulting composition is layered by pressing using, for example, a Manesty press (registered trademark) or a Korsch LCT press. To produce a two-layer core, the drug-containing layer is first pressed; then a wet mixture of the pusher layer, produced by a similar wet granulation technique, is pressed against the drug-containing layer. The compressed two-layer core is coated with a water-soluble polymer, if required, and then covered with a semipermeable membrane material as described above.One or more outlets (openings) are provided at the end of the drug layer of the composition. If necessary, a water-soluble topcoat can be applied, and the topcoat can be colored or transparent. Furthermore, for example, when a dry granulation technique is used as an alternative method, a premixed composition is transformed into a layered product using a roller compression molding machine, and the layered product is crushed into granules and size-graded using a screened crusher with a crushing mechanism. A lubricant, such as magnesium stearate, was added to the graded granules in the same way as before, mixed into the granules using a mixer, and pressed in the same manner as in the production method described above. The osmotic pump composition is provided with at least one release port. The release port is provided either during the manufacture of the composition or during drug delivery by placing the composition in a liquid environment at the time of use. The term "release port" includes, for example, passages, openings, orifices, and lumens (perforations). This term also includes openings formed by erosion, dissolution, or leaching of a substance or polymer from the outer wall. The substance or polymer includes, for example, erodible poly(glycolic acid) or poly(lactic acid) in the semipermeable membrane; gelatinous filaments; water-removable poly(vinyl alcohol); and leachable compounds such as fluid-removable opening-forming substances selected from the group consisting of inorganic salts, organic salts, oxides, and carbohydrates.The release port can be formed, for example, by leaching at least one substance selected from the group consisting of sorbitol, mannitol, lactose, fructose, maltitol, maltose, dextrin, glucose, mannose, galactose, talose, sodium chloride, potassium chloride, and sodium citrate to provide orifices with a pore size suitable for the uniform release of a drug. The release port can be any shape, such as round, rectangular, square, or elliptical, provided the drug can be released from the composition at a uniform rate. The osmotic pump composition can have one or more release ports provided at regular intervals. The size of the release port orifice is not particularly limited, as long as the drug release can be controlled in conjunction with the compression core. Preferably, the size of the release port orifice is from 0.1 mm to 3 mm.To form a release port, for example, a perforation technique through the semipermeable membrane, such as mechanical perforation and laser perforation, can be used. Devices for forming such a release port are known (e.g., U.S. Patent 3,916,899 and U.S. Patent 4,088,864). The amount of the salt of compound (I) in the oral pharmaceutical composition is, for example, in the range of less than 1 mg to 200 mg or more, per dosage form, in terms of the weight of the free base. For example, the drug layer of the osmotic pump composition described below in the Examples contains compound (I) in an amount of 30 mg (in terms of free base). The osmotic pump composition has a half-life (TgO) of approximately 10 hours or more. The salt of compound (I) begins to be released at a uniform rate within approximately 3 to 4 hours after administration, and the release at a uniform rate continues for a long period of at least approximately 12 hours. Thereafter, drug release continues for several hours until the formulation is consumed. Oral pharmaceutical compositions according to this description preferably release the drug at a relatively uniform rate over a long period of time. When administered to a patient, the oral pharmaceutical composition according to this description provides plasma drug concentrations in the patient that fluctuate less over a long period of time than those obtained with conventional pharmaceutical agents (e.g., immediate-release formulations).When the oral pharmaceutical composition is administered according to the present description, a peak occurs at a time later than the appearance of a maximum steady-state plasma concentration after administration of conventional pharmaceutical agents (e.g., immediate-release formulations), and the peak is lower than the peak observed after administration of conventional pharmaceutical agents; consequently, the composition can provide a therapeutically effective mean steady-state blood concentration. This description includes a method for treating pathological conditions and ailments responsive to treatment with compound (I) by oral administration of the oral pharmaceutical composition described herein to a patient. This method is practiced with a formulation suitable for the release of compound (I) at a uniform rate over a period of at least approximately 4 hours, preferably 5 to 30 hours, more preferably 10 to 24 hours, and even more preferably 15 to 24 hours. For the treatment of schizophrenia, the above method is preferred, which involves administering the oral pharmaceutical composition described herein to a patient less than once daily. Other disease states and conditions that may be clinically diagnosed as symptoms of schizophrenia may be treated with the controlled-release oral pharmaceutical composition described herein. Although not limiting, the oral pharmaceutical composition according to the present description preferably maintains a steady-state blood concentration of compound (I) in the range of, for example, 15 ng / mL to 400 ng / mL, or 50 ng / mL to 300 ng / mL, for 1 week, when administered orally to a human (in particular, an adult human). Ordinary tablets (non-controlled-release formulations) containing compound (I) in 0.5 mg, 1 mg, and 2 mg strengths are already commercially available in many countries, including Japan, the United States, and Europe. These ordinary tablets have been confirmed as safe and effective against CNS disorders, such as schizophrenia, in clinical trials, and detailed pharmacokinetic analysis has been performed. Based on the information regarding ordinary tablets, it can be understood that any oral pharmaceutical composition capable of maintaining a steady-state blood concentration of compound (I) in the range of, for example, 15 ng / mL to 400 ng / mL, or 50 ng / mL to 300 ng / mL, when administered to a human, can be used to prevent or treat a CNS disorder, such as schizophrenia, in the same manner as the commercially available ordinary tablets. Therefore, the oral pharmaceutical composition according to this description can be administered orally less frequently than once a day; for example, it can be administered orally once a week. The oral pharmaceutical composition according to this description can be administered as one tablet at a time, or two or more tablets at a time; for example, it can be administered as two tablets, three tablets, four tablets, or five tablets at a time. Persons skilled in the art will be able to appropriately determine the dosage of the oral pharmaceutical composition according to this description to achieve the above blood concentration based, for example, on pharmacokinetic information for ordinary tablets; and assessments based on the single-dose administration protocol and the multiple-dose administration protocol for the oral pharmaceutical composition according to this description.For example, the dosage per dose can be 5 to 60 mg, 10 to 60 mg, 20 to 60 mg, or 45 to 60 mg, in terms of the weight of the free base of the compound (I). As described above, among the oral pharmaceutical compositions according to this description, a particularly preferred embodiment is an oral solid pharmaceutical formulation of an osmotic pump-controlled release system. Of the oral solid pharmaceutical formulations of an osmotic pump-controlled release system, the particularly preferred embodiments are described in more detail below. Note that the following description may partially overlap with the preceding description. The following description does not preclude the application of the preceding description. The oral solid pharmaceutical formulation of an osmotic pump-controlled release system preferably has a structure in which a core formulation formed by laminating a drug layer and a pusher layer is coated with a semipermeable membrane, and the drug layer comprises a salt of compound (I). One embodiment of the formulation includes the formulation shown in Fig. 12. The mass ratio of the drug layer with respect to MA / a / zuzz / uun zoo to the push layer is, for example, approximately 20 to 125 parts by mass of push layer to 100 parts by mass of drug layer. The upper or lower limit of this range is, for example, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, or 120 parts by mass. The range can be, for example, 35 to 100 parts by mass, or 40 to 60 parts by mass. The mass ratio of the drug layer to the pusher layer may be, for example, in the range of approximately 0.8 to 5. The upper or lower limit of the mass ratio may be, for example, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8 or 4.9. For example, the mass ratio of the drug layer to the pusher layer may be in the range of approximately 1 to 4, or approximately 2 to 3. More specifically, the mass ratio may be 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0. The salt of compound (I) is not particularly restricted, provided it is a pharmaceutically acceptable salt. Examples include the various metal salts mentioned above, salts of inorganic bases, salts of organic bases, salts of inorganic acids, salts of organic acids, and the like. The salt is preferably, for example, a fumaric acid salt, a hydrochloric acid salt, a sulfuric acid salt, or the like, and particularly preferably a fumaric acid salt. The term "salt" includes solvates of salts and may be present in solvate form in the pharmaceutical formulation. Examples of solvates include hydrates, methanol solvate, ethanol solvate, and the like. The solvate may be a monosolvate, disolvate, trisolvate, or similar. For example, the solvate may be a monohydrate, a dihydrate, a trihydrate, or similar. A particularly preferred example of such a salt solvate is fumarate monohydrate. The amount of the salt of compound (I) in the drug layer may be, for example, in the range of approximately 5 to 200 mg in terms of the weight of the free base. The upper or lower limit of this range is, for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, or 195 mg. The amount of the salt of compound (I) may be, for example, in the range of approximately 5 to 60 mg, approximately 15 to 150 mg, or approximately 20 to 100 mg, in terms of the weight of the free base of compound (I). The amount of the salt of compound (I) contained in the drug layer can be, for example, from approximately 1 to 35% by mass of the drug layer. The upper or lower limit of the interval is, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, or 34% by mass. The interval may be, for example, from 2 to 30% by mass or from 5 to 20% by mass. In addition to salt, the drug layer may contain additives, such as an osmotic agent and a hydrophilic polymer. The osmotic agent contained within the drug layer is not particularly limited, provided it presents an osmotic pressure gradient across the semipermeable membrane. Examples include inorganic salts, inorganic acids, organic salts, organic acids, saccharides, sugar alcohols, and the like. Examples of inorganic salts include sodium chloride, sodium bicarbonate, sodium carbonate, sodium phosphate (trisodium phosphate), potassium phosphate (tripotassium phosphate), sodium acid phosphate (sodium dihydrogen phosphate, disodium acid phosphate), potassium acid phosphate (potassium dihydrogen phosphate, dipotassium acid phosphate), potassium chloride, lithium chloride, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, sodium sulfite, potassium sulfite, lithium sulfate, potassium acid phosphate, and the like. Examples of inorganic acids include acids that form the inorganic salts mentioned above.Examples of organic salts include sodium fumarate (disodium fumarate), sodium hydrogen fumarate (monosodium fumarate), sodium hydrogen tartrate, potassium hydrogen tartrate, sodium tartrate, sodium potassium tartrate, sodium malate (disodium malate), sodium hydrogen succinate, sodium succinate (disodium succinate), sodium hydrogen maleate, sodium maleate (disodium maleate), sodium hydrogen citrate (sodium dihydrogen citrate, disodium hydrogen citrate), sodium citrate (trisodium citrate), and the like. Examples of organic acids include acids that form the organic salts mentioned above. Examples of sugars and sugar alcohols include mannitol, glucose, lactose, fructose, sucrose, sorbitol, xylitol, erythritol, and the like. These can be anhydrides or solvates (such as hydrates). They can be used alone or in combination with one or more others.The osmotic agent contained in the drug layer preferably shares a common ion with the compound's salt (I). For example, when the salt is a fumarate, examples of osmotic agents sharing a common ion with fumarate include fumaric acid, monosodium fumarate, disodium fumarate, and similar agents. The osmotic agent can be used alone or in combination with two or more. The osmotic agent content in the drug layer is, for example, approximately 1 to 50% by mass, based on the weight of the drug layer. The upper or lower limit of the range is, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, or 49% by mass. For example, the range can be from 10 to 38% by mass or from 15 to 35% by mass. Examples of hydrophilic polymers contained in the drug layer include polyethylene oxide, polyethylene glycol, and similar materials. Preferably, the polyethylene oxide is a low-viscosity polyethylene oxide. More specifically, the polyethylene oxide is preferably a polyethylene oxide having an average molecular weight of approximately 100,000 to 300,000, and more preferably a polyoxyethylene oxide having an average molecular weight of approximately 150,000 to 250,000, or 180,000 to 220,000. Preferably, the polyethylene glycol is, for example, one in which, on average, 4,000 to 8,000, preferably 4,500 to 7,500, 5,000 to 7,000, or 5,500 to 6,500 units of ethylene oxide are polymerized.To inhibit drug recrystallization in the formulation, the drug layer may contain, as a hydrophilic polymer, a water-soluble cellulose-based polymer such as methylcellulose, hydroxypropylcellulose, hydroxypropylcellulose (e.g., hydroxypropyl ethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl butylcellulose, and hydroxypropyl pentylcellulose), polyvinyl alcohol, a polyvinyl alcohol-polyethylene glycol graft copolymer, polyvinylpyrrolidone, copovidone, and the like. Hydroxypropylalkyl cellulose is particularly preferable to hydroxypropylmethylcellulose. Hydroxypropylmethylcellulose preferably has a methoxy group content of, for example, approximately 16 to 30%, and more preferably 27 to 30%. The hydrophilic polymers may be used individually or in combination with two or more types. As described above, the oral pharmaceutical composition according to the present description preferably comprises a drug-containing composition with a water-soluble cellulose polymer. Accordingly, the drug layer preferably contains a water-soluble cellulose-based polymer as the hydrophilic polymer. The hydrophilic polymer content of the drug layer is, for example, approximately 5 to 94% by mass of the drug layer. The upper or lower limits of the interval are, for example, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 84, 85, 86, 87, 88, 89, 90, 91, 92 or 93% by mass. For example, the range can be from 20 to 90% by mass. When the drug-containing composition contains in particular a water-soluble cellulose-based polymer, the content of the water-soluble cellulose-based polymer in the drug layer is, for example, approximately 5 to 40% by mass, or approximately 10 to 30% by mass, or approximately 10 to 20% by mass, based on the weight of the drug layer. When the drug layer contains particularly (i) polyethylene oxide and (ii) at least one member selected from the group consisting of hydroxypropylcellulose, methylcellulose, hydroxypropylalkylcellulose, polyvinyl alcohol, a polyvinyl alcohol-polyethylene glycol graft copolymer, polyvinylpyrrolidone and copovidone simultaneously as hydrophilic polymers, the content of component (i) may be from 10 to 60% by mass and the content of component (ii) may be from approximately 5 to 40% by mass, based on the weight of the drug layer. The drug layer may also contain other additives. Examples of additives include lubricants, fluidizers, and the like. Examples of preferred lubricants include magnesium stearate. Examples of preferred fluidizers include silicon dioxide (in MA / a / zuzz / uun zoo particular, light anhydrous silicic acid). The drug layer contains a lubricant (in particular, magnesium stearate), for example, in an amount of approximately 0.1 to 5% by mass or approximately 0.2 to 3% by mass, based on the weight of the drug layer. The drug layer may contain a fluidizer (in particular, silicon dioxide) in an amount of, for example, 0.1 to 5% by mass or approximately 0.1 to 3% by mass, based on the weight of the drug layer. The booster layer also comprises a component for extruding a salt of compound (I). Examples of the component include a highly swellable polymer. Examples of highly swellable polymers include polyalkylene oxide and, more specifically, polyethylene oxide. Preferably, the polyethylene oxide contained in the booster layer is a high-viscosity polyethylene oxide; and more specifically, for example, a polyethylene oxide having an average molecular weight of, for example, approximately 3,000,000 to 7,000,000, approximately 4,000,000 to 7,000,000, or approximately 4,000,000 to 6,000,000. The amount of highly swellable polymer in the push layer can vary depending on factors such as the properties and content of the drug in the drug layer; however, it can be any amount that allows the drug to elute from the drug layer at a desired release rate by swelling. For example, the content of the highly swellable polymer is 50 to 90% by mass, 50 to 85% by mass, 50 to 80% by mass, 55 to 75% by mass, or approximately 60 to 70% by mass, based on the weight of the push layer. The pusher layer may also contain other additives. For example, the pusher layer may contain an osmotic agent. Examples of osmotic agents in the pusher layer include inorganic salts, inorganic acids, organic salts, organic acids, saccharides, sugar alcohols, and the like. Examples of inorganic salts include sodium chloride, sodium bicarbonate, sodium carbonate, sodium phosphate (trisodium phosphate), potassium phosphate (tripotassium phosphate), sodium biphosphate (sodium dihydrogen phosphate, disodium hydrogen phosphate), potassium biphosphate (potassium dihydrogen phosphate, dipotassium hydrogen phosphate), potassium chloride, lithium chloride, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, sodium sulfite, potassium sulfite, lithium sulfate, potassium acid phosphate, and the like. Examples of inorganic acids include acids that form the inorganic salts described above.Examples of organic salts include sodium fumarate (disodium fumarate), sodium hydrogen fumarate (monosodium fumarate), sodium hydrogen tartrate, potassium hydrogen tartrate, sodium tartrate, potassium sodium tartrate, sodium malate (disodium malate), sodium hydrogen succinate, sodium succinate (disodium succinate), sodium hydrogen maleate, sodium maleate (disodium maleate), sodium hydrogen citrate (sodium dihydrogen citrate, disodium hydrogen citrate), sodium citrate (trisodium citrate), and the like. Examples of organic acids include acids that form the organic salts described above. Examples of saccharides and sugar alcohols include mannitol, glucose, lactose, fructose, sucrose, sorbitol, xylitol, erythritol, and the like. These can be anhydrides or solvates (such as hydrates). Preferred examples of osmotic agents contained in the push layer include sodium chloride, potassium chloride, sodium hydrogen fumarate, sodium fumarate, sodium bicarbonate, sodium carbonate, sodium hydrogen phosphate, sodium phosphate, potassium hydrogen phosphate, potassium phosphate, sodium sulfate, fructose, sucrose, xylitol, sorbitol, glucose, mannitol, erythritol, and lactose. Sodium bicarbonate is particularly preferred. Such osmotic agents can be used alone or in a combination of two or more. In the thrust layer, the osmotic agent is preferably present in an amount of, for example, 5 to % by mass, 15 to 50% by mass, 20 to 50% by mass, 25 to % by mass, or approximately 30 to 40% by mass based on the weight of the thrust layer. The thrust layer may also contain other additives. Examples of such additives include lubricants, fluidizers, pigments, and the like. Preferred examples of lubricants include magnesium stearate. Preferred examples of fluidizers include silicon dioxide (particularly light anhydrous silicic acid). Preferred examples of pigments include iron oxide. The thrust layer may contain a lubricant (in particular, magnesium stearate) in an amount of, for example, 0.1 to 5% by mass, relative to the weight of the thrust layer. The thrust layer may contain a fluidizer (in particular, silicon dioxide) in an amount of, for example, approximately 0.1 to 5% by mass or 0.1 to 3% by mass, based on the weight of the thrust layer. In addition, the thrust layer may contain a pigment (in particular, iron oxide) in an amount of, for example, 0.1 to 2% by mass. The semipermeable membrane coating the core formulation includes, for example, a cellulose-based polymer, preferably cellulose acetate, as described above. The semipermeable membrane may also contain a flow-regulating agent. As described above, the flow-regulating agent is preferably, for example, polyethylene glycol (in particular, polyethylene glycol having an average molecular weight of approximately 2000 to 6000, approximately 3000 to 5000, or approximately 3000 to 6000). The semipermeable membrane may contain a cellulose polymer in an amount of, for example, approximately 70 to 100% by mass, or 75 to 95% by mass, based on the weight of the semipermeable membrane. The semipermeable membrane may contain a flow-regulating agent in an amount of approximately 0.01 to 30% by mass or approximately 5 to 25% by mass, based on the weight of the semipermeable membrane. The amount of coating on the semipermeable membrane is preferably an amount that allows high permeability to external fluids, such as water and biological fluids, and is substantially impermeable to the salts of compound (I), highly swellable polymers, and the like. The amount of semipermeable membrane may be, for example, approximately 5 to 25 parts by mass per 100 parts by mass of the core formulation. The upper or lower limit of this range is, for example, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 parts by mass. A water-soluble polymer coating can be applied between the core formulation and the semipermeable membrane in the oral solid pharmaceutical formulation of an osmotic pump-controlled release system. In other words, the formulation can have a structure in which a water-soluble polymer membrane and a semipermeable membrane (preferably applied as a coating) are laminated to the core formulation in that order. The water-soluble polymer membrane may contain, as water-soluble polymers, those described above as hydrophilic polymers that can be embedded in the drug layer. Among such polymers, for example, hydroxypropyl methylcellulose, polyvinyl alcohol, a graft copolymer of polyethylene glycol and polyvinyl alcohol, and polyvinylpyrrolidone are preferred. Such water-soluble polymers may be used alone or in combination. When the water-soluble polymer membrane contains hydroxypropyl methylcellulose, for example, 60 to 100% by mass of the water-soluble polymer film may be hydroxypropyl methylcellulose. When the water-soluble polymer membrane contains polyvinylpyrrolidone, for example, 0 to 40% by mass of the water-soluble polymer film may be polyvinylpyrrolidone. The water-soluble polymer membrane may be present, for example, in an amount of approximately 1 to 15 parts by mass, per 100 parts by mass of the core formulation. The oral solid pharmaceutical formulation described herein can be used, for example, as plain tablets containing the components mentioned above and without a colored coating. For instance, to impart a distinctive character to the formulation, ensure long-term storage stability, and prevent degradation by light, it is preferable to manufacture tablets coated with a colored coating. If necessary, the coating may additionally contain pharmaceutical additives commonly used in the coating (film-forming) of oral pharmaceuticals, such as a coating agent, a plasticizer, a dispersant, and an antifoaming agent. If a colored coating is provided, it is preferably the outermost layer.A known coating agent may be used for the color coating layer. For example, a representative premix additive, such as Opadry, may be used as a coating agent. Preferred examples include coating agents comprising hydroxypropyl methylcellulose, polyvinyl alcohol, a polyvinyl alcohol-polyethylene glycol graft copolymer, a polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, or similar base materials; and further comprising a coloring agent, a lubricant, a plasticizer, or similar components. A preferred example of the oral solid pharmaceutical formulation of an osmotic pump-controlled release system according to the present description is a formulation comprising a core formulation comprising a drug layer and a pusher layer, wherein the drug layer comprises 200 mg of a salt of compound (I) on a weight basis of the freebase, 50% by mass of an additive containing an ion in common with the salt, based on the weight of the drug layer, and 94% by mass of a hydrophilic polymer, based on the weight of the drug layer. 0.1 to 5% by mass of a lubricant, based on the weight of the drug layer, and 0.1 to 5% by mass of a fluidifier, based on the weight of the drug layer, the booster layer comprising 90% by mass of a highly swellable polymer, based on the weight of the booster layer, to 50% by mass of an osmotic agent, based on the weight of the booster layer, 0.1 to 5% by mass of a lubricant, based on the weight of the thrust layer, and 0.1 to 2% by weight of a pigment, based on the weight of the push layer, the core formulation comprises 5 to 25 parts by mass of a semipermeable membrane and 1 to 15 parts by mass of a water-soluble polymeric membrane, based on 100 parts by mass of the core formulation, the semipermeable membrane comprises 70 to 100% by mass of a cellulose-based polymer and 0.01 to 30% by mass of a water-soluble flow-regulating agent, based on the weight of the semipermeable membrane, and the core formulation optionally comprises a color coating layer. As described above, another preferred embodiment of the oral pharmaceutical composition according to the present description may be, for example, a sustained-release hydrogel composition. More specifically, the sustained-release hydrogel composition (sustained-release hydrogel formulation) according to the present description contains a salt of compound (I) as the active ingredient and further contains an additive that shares an ion with the salt. The sustained-release hydrogel composition is MA / a / zuzz / uun zoo preferably, for example, a hydrogel matrix tablet. Hydrogel matrix tablets are a known technique in which the release of a drug is controlled by a hydrogel, which is formed by (in the case of an enteric-coated tablet, the dissolution of the coating film due to an increase in pH after gastric excretion, and then) absorption of water in the gastrointestinal tract. The hydrophilic polymers mentioned above can be used as the sustained-release base (hydrogel-forming base) in the hydrogel matrix tablet, for example. Specific examples of usable bases include water-soluble polymers based on cellulose, polyalkylene oxide (e.g., polyethylene oxide), polyalkylene glycol (e.g., polyethylene glycol), polyvinyl alcohol, and similar materials. The above hydrophilic polymers can be used as the sustained-release base material, either alone or in combination. It is particularly preferable that the sustained-release base material contain at least one water-soluble polymer based on cellulose.When a hydrophilic polymer other than water-soluble cellulose-based polymers (e.g., polyethylene oxide) is primarily used as a sustained-release base, the hydrophilic polymer is preferably combined with at least one water-soluble cellulose-based polymer. As a water-soluble cellulose-based polymer, for example, a water-soluble cellulose-based polymer known in the field of pharmaceutical science may be used preferably. Preferred examples include water-soluble cellulose-based polymers that have a structure in which the hydrogen atoms of some of the cellulose OH groups are replaced with methyl and / or hydroxypropyl groups. Specific examples include hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcellulose, and the like. Water-soluble cellulose-based polymers may be used alone or in a combination of two or more. The water-soluble cellulose-based polymer can be any water-soluble cellulose-based polymer. For example, a water-soluble cellulose polymer with a viscosity of 2.5 to 35,000 mm² / s, measured as a 2% aqueous solution, can be used. It is particularly preferable to use a water-soluble cellulose-based polymer with a viscosity of 2.5 to 17.5 mm² / s, measured as a 2% aqueous solution. When a water-soluble cellulose-based polymer (e.g., hypromellose) is used primarily as a sustained-release base, the water-soluble cellulose-based polymer has a viscosity of 80 to 35000 mm2 / s measured in MA / a / zuzz / uun zoo form of a concentration of an aqueous solution 2%. The phrase "primarily using the hydrophilic polymer" in this document means that the amount of the hydrophilic polymer is 50% by mass or more, for example, 80% by mass or more, or 90% by mass or more, based on the total mass of the sustained-release base. The tablet core may contain the sustained-release base in an amount of, for example, approximately 30 to 90% by mass, or approximately 50 to 80% by mass, based on the weight of the tablet core. The additives described above can be appropriately used as the additive containing a common ion with the salt of compound (I) in the hydrogel matrix tablet. The hydrogel matrix tablet can contain the additive in an amount of, for example, approximately 1 to 50% by mass, or approximately 10 to 30% by mass, based on the mass of the tablet core. The hydrogel matrix tablet may also contain other additives. Examples of additives include lubricants, fluidizers, and the like. Examples of preferred lubricants include magnesium stearate and the like. The hydrogel matrix tablet may contain a lubricant in an amount of, for example, 0.1 to 5% by mass, or 0.2 to 3% by mass, based on the weight of the tablet core. Examples of preferred fluidizers include silicon dioxide (in particular, light anhydrous silicic acid). The hydrogel matrix tablet may contain a fluidizer in an amount of, for example, approximately 0.1 to 5% by mass, or approximately 0.1 to 3% by mass, based on the mass of the tablet core. The hydrogel matrix tablet preferably comprises an enteric coating. A known enteric coating composition can be used for the enteric coating. For example, an enteric coating composition containing an enteric base such as Eudragit, a plasticizer such as triethyl citrate, and a lubricant such as talc can preferably be used. The hydrogel matrix tablet preferably contains an enteric coating in an amount of, for example, approximately 1 to 40 parts by mass, or 10 to 30 parts by mass, per 100 parts by mass of the tablet core. A preferred example of the sustained-release hydrogel formulation according to the present description is a formulation containing 5 to 200 mg of a salt of compound (I) on a weight basis of the free base of compound (I); further containing 1 to 50% by mass of an additive having an ion in common with a salt of compound (I) on a mass basis of the tablet core, 30 to 90% by mass of a sustained-release base material on a mass basis of the tablet core, and 0.1 to 5% by mass of a lubricant on a weight basis of the tablet core; and further comprising an enteric coating in an amount of 1 to 40 parts by mass on a 100 parts by mass basis of the tablet core. In this specification, the term "comprising" includes components that essentially consist of and components that consist of. Furthermore, this description includes any and all combinations of the components described herein. Various characteristics (properties, structures, functions, etc.) described in the preceding modalities of this description may be combined in any way to specify the subject matter included in this description. That is, this description includes all subject matter comprising any combination of the combinable properties described herein. Examples The present invention is described more specifically below with reference to Examples, Test Examples, etc. However, the present description is not limited to these Examples. Compound (I) means 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one. Preparation of 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-l-yl)-butoxy]-lH-quinolin-2-one fumarate A suspension of 4.22 kg of fumaric acid in 32.5 L of water and 22.16 kg of ethanol was stirred under reflux to dissolve the fumaric acid (reflux temperature: approximately 82°C). The resulting solution was filtered while washing with 11.86 kg of ethanol to obtain a fumaric acid solution. A suspension of 15.0 kg of 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-l-yl)-butoxy]-lH-quinolin-2-one in 25.96 kg of water, 8.32 kg of acetic acid, and 34.0 L of ethanol was stirred under reflux to dissolve 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-l-yl)-butoxy]-lH-quinolin-2-one (reflux temperature: approximately 83°C). The resulting solution was added to fumaric acid solution and then filtered while washing with 11.86 kg of ethanol. The filtrate was stirred under reflux for 15 minutes (reflux temperature: approximately 82°C), then cooled to 30°C or lower and separated into a solid and a liquid. The resulting solid was washed with water, dried at 80°C and then moistened to obtain 16.86 kg of quinolin-2-one 7—[4—(4—benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-1H- fumarate. Infrared absorption spectrum The IR spectrum of the fumaric acid salt prepared by the above method was measured by the KBr tablet method using a Fourier transform infrared spectrophotometer (IRPrestige-21) manufactured by Shimadzu Corporation. As shown in Fig. 11, the IR spectrum showed absorption at wavenumbers of 3657 cm⁻¹, 1711 cm⁻¹, 1643 cm⁻¹, and 1711 cm⁻¹. 1416 cm-1, 122 7 cm-1 and 83 9 cm-1. X-ray diffraction in powder The powder X-ray diffraction of the fumaric acid salt prepared by the above method was measured using a Bruker AXS D8 ADVANCE X-ray diffractometer. Figure 11b shows the powder X-ray diffraction pattern of the fumaric acid salt. As shown in Figure 11b, diffraction peaks were observed at 2Θ = 7.6°, 15.1°, 17.7°, 18.9°, and 19.2°. Other peaks were observed at 2Θ = 9.8°, 11.3°, 12.2°, 14.0°, 16.5°, 17.0°, 21.2°, 22.3°, 22.7°, 23.8°, 24.2°, 24.7°, 25.4°, 26.5°, 26.9°, 27.9°, 28.9°, 31.9°, 32.3°, 32.6° and 34.2°. Water content measurement The water content of the prepared fumaric acid salt was measured. Specifically, the water content was measured by the Karl Fischer method (coulometric titration method) using a water content measuring device (Titrando 852) manufactured by Metrohm. The results confirmed that the water content of the fumaric acid salt was 3.01% by weight. Preparation of sustained-release drug formulation and evaluation 1 An osmotic pump-controlled release composition (formulation) was produced comprising a two-layer compressed core comprising a drug layer for providing sustained release of a salt of compound (I) and a booster layer according to a known general production process. More specifically, a drug layer composition containing a salt of compound (I) and other inert agents, and a booster layer composition containing an osmotic agent and a highly viscous polymer were produced separately; and each composition was then compressed into a two-layer tablet core using a known core compression technique. Subsequently, the two-layer compressed core was coated with a composition comprising a water-soluble polymer. The water-soluble polymer composition consisted of hypromellose (hydroxypropyl methylcellulose; TC-5, produced by Shin-Etsu Chemical Co., Ltd.) and povidone (polyvinylpyrrolidone; Kollidon K30, BASF) (70:30 (% w / w)) dissolved in water to 8% solids content to prepare a coating solution. This water-soluble polymer coating solution was applied to the two-layer compressed core as prepared above using a drum coater until the coating component represented 10% of the mass of the two-layer compressed core. Furthermore, the resulting two-layer compressed core with a water-soluble coating was coated with a semipermeable membrane composition. The semipermeable membrane composition consisted of cellulose acetate and polyethylene glycol 4000 (85:15 (w / w%)) dissolved at 5% solids content in acetone / water (95:5 (w / w%)) as a solvent, thus yielding a coating solution. This coating solution was applied to the previously produced two-layer compressed core with the water-soluble coating using a drum coater until the coating component represented 10% of the mass of the two-layer compressed core. The coated core was then removed from the drum coater and subjected to a drying treatment at 40°C for 24 hours using a grid dryer. The thus coated two-layer compressed core was provided with drug release ports that had a diameter of 0.8 mm on the surface of the drug layer side using an automated laser to prepare an osmotic pump formulation. Table 1 below shows the components of the MA / a / zuzz / uun zoo osmotic pump formulation. Table 1 MA / a / ZUZZ / UUI / 00 Formulation (mg / unit) Example 1-1 Example 1-2 Example 1-3 Example 1-4 Example 1-5 Tablet Core Components Drug Layer Fumaric Acid Salt of Compound (I) 39.27 39.27 39.27 39.27 39.27 Low Viscosity Polyethylene Oxide 89.73 89.73 89.73 89.73 89.73 Fumaric Acid 30.00 - - - - Monosodium Fumarate - 30.00 — — — Sodium Hydrogen Carbonate 30.00 D-Mannitol - - - 30.00 - Polyethylene Glycol 6000 - — — — 30.00 Magnesium Stearate 1.00 1.00 1.00 1.00 1.00 Pusher Layer High Viscosity Polyethylene Oxide 45.40 45.40 45.40 45.40 45.40 Sodium bicarbonate 24.00 24.00 24.00 24.00 24.00 Iron oxide 0.20 0.20 0.20 0.20 0.20 Magnesium stearate 0.40 0.40 0.40 0.40 0.40 Subtotal 230.00 230.00 230.00 230.00 230.00 Coating components Water-soluble polymer HPMC TC-5R 16.10 16.10 16.10 16.10 16.10 Kollidon K30 6.90 6.90 6.90 6.90 6.90 Components Semipermeable membrane Cellulose acetate 19.55 19.55 19.55 19.55 19.55 PEG 4000 3.45 3.45 3.45 3.45 3.45 Subtotal 46.00 46.00 46.00 46.00 46.00 Total 276.00 276.00 276.00 276.00 276.00. The formulations obtained in the Examples were subjected to the following Test Example 1 and Test Example 2, and were evaluated. As low-viscosity polyethylene oxide, POLYOX (trade name) WSR N-80 was used (average molecular weight: approximately 200,000, viscosity: 55 to 90 mPa-s (5% w / v aqueous solution, 25°C)). As high-density polyethylene oxide, POLYOX (registered trademark) WSR Coagulant was used (average molecular weight: 5,000,000, viscosity: 5,500 to 7,500 mPa-s (1% w / v aqueous solution, 25°C)). Test Example 1 The release rate of the formulations obtained in the Examples was evaluated by measuring the dissolution rate of each salt of compound (I) at intervals of 30 minutes to 2 hours for 24 hours. The dissolution test was performed according to Method 2 of the Dissolution Test of the 15th Japanese Pharmacopoeia (paddle method). 900 mL of a 0.05 mol / L acetate buffer solution (pH approximately 4.3, acetic acid, sodium acetate) was used as the test liquid, and the test was performed at 37°C and a paddle rotation speed of 50 rpm. Sampling was performed over time, and the amount of compound (I) (free base) in the sampling solution was quantified using a UV detector (absorbance measurement wavelengths: 323 nm and 380 nm).The mass proportion (%) of the dissolving compound (I) (free basis) relative to the total mass of compound (I) (free basis) in the formulation, taken as 100%, was defined as the dissolution rate. Since the dissolution rate is the same as the mass proportion (%) of the dissolved salt of compound (I) relative to the total mass of the salt of compound (I) in the formulation, taken as 100%, the dissolution rate can also be used as the dissolution rate of the salt of compound (I). The figure shows the results. The term "Dissolved (%)" in Fig. 1 indicates the dissolution rate. Test Example 2 The release rate of the formulation for each Example was evaluated by measuring the dissolution rate of a salt of compound (I) at 1-hour intervals for 24 hours. The dissolution test was performed according to Method 2 of the Dissolution Test of the 15th Japanese Pharmacopoeia (paddle method). 900 mL of the second dissolution test liquid (pH approximately 7, potassium dihydrogen phosphate, disodium hydrogen phosphate) listed in the Japanese Pharmacopoeia was used as the test liquid, and the test was performed at 37°C and a paddle rotation speed of 50 rpm. Sampling was performed over time, and compound (I) (free base) in the sampling solution was quantified using a UV detector (absorbance measurement wavelengths: 323 nm and 380 nm).The first wavelength (323 nm) was established as the wavelength at which the absorbance of the main drug is maximally detectable, and the second wavelength (380 nm) was established as the wavelength at which the absorbance of the main drug is not detectable. Figure Ib shows the results. In the figure, dissolved (pg / mL) indicates the concentration of the eluted (dissolved) compound (I) (free base). In Test Example 1, the eluate had a pH of approximately 4.3. The results of the dissolution test evaluation in Test Example 1 are an indicator of the extent to which the salt of compound (I) will dissolve throughout the gastrointestinal tract following oral administration of the oral pharmaceutical composition. The sustained release time of the oral pharmaceutical composition can be evaluated from the profile obtained. On the other hand, in Test Example 2, the pH of the eluate was approximately 7. The results of the dissolution test evaluation in Test Example 2 show the level at which the salt of compound (I) elutes in the lower gastrointestinal tract after the oral pharmaceutical composition is administered orally and passes through the stomach. In Test Example 2, the following phenomenon was observed: since the solubility of the salt of compound (I) is greater than the solubility of compound (I), the solution concentration of the salt of compound (I) from the formulation temporarily exceeds the solubility of compound (I), resulting in a supersaturated concentration. Following this, the solution concentration decreases with the recrystallization of compound (I).The profile obtained at that time is defined as a supersaturated dissolution profile and can be evaluated as an indicator of absorbability in the lower part of the gastrointestinal tract. Previous results confirmed that formulations containing particularly fumaric acid or monosodium fumarate as an osmotic agent in the drug layer exhibited excellent supersaturated dissolution profiles (Fig. 1(b)), and were particularly preferable. Preparation of sustained-release drug formulation and evaluation 2 The oral pharmaceutical compositions (osmotic pump formulations) shown in Table 2 were prepared in the same manner as the method described above in the section "Preparation of sustained-release drug formulation and evaluation 1", except that the types and quantities of the tablet core and coating components were changed as shown in Table 2. The formulations obtained in the Examples shown in Table 2 were evaluated in the same manner as before in Test Example 2. Table 2 shows the results. Table 2 Formulation (mg / unit) Example 2-1 Example 2-2 Example 2-3 Example 2-4 Tablet Core Components Drug Layer Fumaric acid salt of compound (I) 39.27 39.27 39.27 39.27 Low viscosity polyethylene oxide 89.73 69.73 69.73 69.73 Monosodium fumarate 30.00 30.00 30.00 30.00 Eipromellose TC-5R - 20.00 - - Low substituted hydroxypropylcellulose 20.00 Polyethylene glycol 6000 - - - 20.00 Magnesium stearate 1.00 1. 00 1.00 1.00 Push Layer High Viscosity Polyethylene Oxide 45.40 45.40 45.40 45.40 Sodium Hydrogen Carbonate 24.00 24.00 24.00 24.00 Iron Oxide 0.20 0.20 0.20 0.20 Magnesium Stearate 0.40 0.40 0.40 0.40 Subtotal 230.00 230.00 230.00 230.00 Coating Components Water-Soluble Polymer EPMC TC-5R 16.10 16.10 16.10 16.10 Kollidon K30 6.90 6.90 6.90 6.90 Membrane Components Semi-Permeable Cellulose Acetate 31.05 31.05 31.05 31.05 PEG 4000 3.45 3.45 3.45 3.45 Subtotal 57.50 57.50 57.50 57.50 Total 287.50 287.50 287.50 287.50 Previous results confirmed that formulations containing particularly hypromellose (hydroxypropyl methylcellulose) as a carrier (particularly a hydrophilic polymer) have an excellent supersaturated solution concentration profile and were found to be more preferable. Preparation of Sustained-Release Drug Formulation and Evaluation 3 The oral pharmaceutical compositions (osmotic pump formulations) shown in Table 3 were prepared in the same manner as the method described above in the section Sustained Drug Release Formulation Preparation and Evaluation 1, except that the types and quantities of the core tablet components and coating components were changed as shown in Table 3. The formulations obtained in the Examples shown in Table 3 were evaluated in the same manner as before in Test Example 1. Fig. 3 shows the results. Table 3 Formulation (mg / unit) Example 3-1 Example 3-2 Example 3-3 Example 3-4 Example 3-5 Example 3-6 Example 3-7 Example 3-8 Example 3-9 Tablet Core Components Drug Layer Compound (I) Futoric Acid Salt 39.27 39.27 39.27 39.27 39.27 39.27 39.27 39.27 39.27 Low Viscosity Polyethylene Oxide 87.73 87.73 87.73 87.73 87.73 87.73 87.73 87.73 87.73 Crospovidone Kollidon CL 16.00 16.00 26.00 16.00 16.00 16.00 16.00 16.00 16.00 Povidone Kollidon K30 16.00 16.00 16.00 16.00 16.00 16.00 16.00 16.00 16.00 Magnesium Stearate 1.00 1.00 1.00 1.00 1.00 1.0C 1.00 1.00 1.00 Erpush layer High viscosity polyethylene oxide 45.40 45.40 45.40 45.40 45.40 45.40 45.40 45.40 45.40 Sodium chloride 24.00 - - - - - - - - D-tphennitol - 24.00 - - - - - - - Fructose - - 24.00 - - - - - - Sucrose - - - 24.00 - - - - - Sorbitol - - - - 24.00 - - - - Sodium bicarbonate - - - - - 24.00 - - - Disodium carbonate - - - - - - 24.00 - - co Sodium dihydrogen phosphate 24.00 Disodium hydrogen phosphate 24.00 Iron oxide 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Magnesium stearate 0.40 0.40 0.40 0.40 0.40 0.40 0.40 0.40 0.40 Subtotal 230.00 230.00 230.00 230.00 230.00 230.00 230.00 230.00 230.00 Coating components Soluble polymer in SCjuUc. HM K-5R 16.10 16.10 16.10 16.10 16.10 16.10 16.10 16.10 16.10 Kollidon K30 6.90 6.90 6.90 6.90 6.90 6.90 6.90 6.90 6.90 Semipermeable Cellulose Acetate Material 19.55 19.55 19.55 19.55 19.55 19.55 19.55 19.55 PEG 4000 3.45 3.45 3.45 3.45 3.45 3.45 3.45 3.45 3.45 Subtotal 46.00 46.00 46.00 46.00 46.00 46.00 46.00 46.00 46.00 Total 276.00 276.00 276.00 276.00 276.00 276.00 276.00 276.00 276.00 ω co The previous results confirmed that the formulations obtained in all the Examples exhibit excellent sustained-release properties (Fig. 3). Furthermore, it was found that when sodium bicarbonate or sodium chloride is used as the osmotic agent in the push layer, the slope of the dissolution rate graph in Fig. 3 is more constant (i.e., the dissolution of the salt of compound (I) continues at a constant rate), and this is preferable from this perspective. It was also found that when sodium chloride was used, the final dissolution rate obtained was slightly lower than that achieved when other osmotic agents were used. Based on the previous results, the use of sodium bicarbonate was found to be particularly preferable because a high final dissolution rate is obtained and the dissolution continues at a constant rate. Preparation of Sustained-Release Drug Formulation and Evaluation 4 The oral pharmaceutical compositions (osmotic pump formulations) shown in Table 4 were prepared in the same manner as the method described above in the section Sustained-Release Drug Formulation Preparation and Evaluation 1, except that the types and amounts of the tablet core components and coating components were changed as shown in Table 4. The formulations obtained in the Examples shown in Table 4 were evaluated in the same manner as before in Test Examples 1 and 2. However, in Test Example 1 of the evaluation, a liquid was prepared by adding a surfactant (cetyl-11rimethicone bromide: CTAB) to a final concentration of 0.5% w / w of the test liquid used in Test Example 2.This test solution was prepared so that the added surfactant increases the solubility of compound (I) at a pH of approximately 7 and allows for 100% dissolution of the drug from the formulation. This test solution was used because it was considered most appropriate for evaluating the release of the formulation under pH conditions throughout the gastrointestinal tract. Figures 4a and 4b show the results. Table 4 Formulation (mg / unit) Example 4-1 Example 4-2 Example 4-3 Tablet Core Components Drug Layer Fumaric Acid Salt of Compound (I) 39.27 39.27 39.27 Low Viscosity Polyethylene Oxide 59.73 59.73 59.73 Monosodium Fumarate 40.00 40.00 40.00 Hypromellose TC-5R 20.00 20.00 20.00 Magnesium Stearate 1.00 1.00 1.00 Push Layer High Viscosity Polyethylene Oxide 45.40 45.40 45.40 D-Mannitol 24.00 - - Sodium Hydrogen Carbonate — 24.00 — Fructose - - 24.00 Iron Oxide 0.20 0.20 0.20 Magnesium Stearate 0.40 0.40 0.40 Subtotal 230.00 230.00 230.00 Coating Components Water-Soluble Polymer HPMC TC-5R 16.10 16.10 16.10 Kollidon K30 6.90 6.90 6.90 Semipermeable Membrane Components Cellulose Acetate 36.80 36.80 36.80 PEG 4000 9.20 9.20 9.20 Subtotal 69.00 69.00 69.00 Total 299.00 299.00 299.00 Preparation of sustained-release drug formulation and evaluation 5 The oral pharmaceutical compositions (osmotic pump formulations) shown in Table 5 were prepared in the same manner as the method described above in the section Preparation of Sustained-Release Drug Formulation and Evaluation 1, except that the types and quantities of the tablet core components and coating components were changed as shown in Table 5. The formulations obtained in the Examples shown in Table 5 were evaluated in the same manner as before in Test Examples 1 and 2. Figures 5a and 5b show the results. Table 5 IVIA / a / ZUZZ / UU I zoo Formulation (mg / unit) Example 5-1 Example 5-2 Example 5-3 Tablet Core Components Drug Layer Fumaric acid salt of compound (I) 39.27 39.27 39.27 Low viscosity polyethylene oxide 69.73 69.73 69.73 Monosodium fumarate 30.00 30.00 30.00 Hypromellose TC-5R 20.00 20.00 20.00 Magnesium stearate 1.00 1.00 1.00 Push-off layer High viscosity polyethylene oxide 45.40 45.40 45.40 Sodium hydrogen carbonate 24.00 24.00 24. Iron oxide 0.20 0.20 0.20 Magnesium stearate 0.40 0.40 0.40 Subtotal 230.00 230.00 230.00 Coating components Water-soluble polymer HPMC TC-5R 16.10 16.10 16.10 Kollidon K30 6.90 6.90 6.90 Semipermeable membrane components Cellulose acetate 20.70 31.05 41.40 PEG 4000 2.30 3.45 4.60 Subtotal 46.00 57.50 69.00 Total 276.00 287.50 299.00 These results confirmed that the formulations obtained in all the Examples showed excellent sustained-release properties (Fig. 5(a)). It was also confirmed that the sustained-release time can be controlled by changing the amount of the film component (semipermeable component). Even when hypromellose with a different aqueous solution viscosity was used in the drug layer (more specifically, when hypromellose TC-5E with a viscosity of approximately 3 mPa-s measured at 20°C as a 2% aqueous solution was used instead of hypromellose TC5R, which has a viscosity of approximately 6 mPa-s measured at 20°C as a 2% aqueous solution), the viscosity difference did not significantly affect the sustained release and the supersaturation maintenance effect. Preparation of sustained-release drug formulation and evaluation 6 The oral pharmaceutical compositions (osmotic pump formulations) shown in Table 6 were prepared in the same manner as the method described above in the section "Preparation of sustained-release drug formulation and evaluation 1", except that the types and quantities of the tablet core components and coating components were changed as shown in Table 6. The formulations obtained in the Examples shown in Table 6 were evaluated in the same manner as before in the Test Examples 1 and 2. However, in Test Example 1 of the evaluation, a liquid prepared by adding a surfactant (cetyltrimethylammonium bromide: CTAB) to a final concentration of 0.5% w / w of the test liquid used in Test Example 2 was used as the test liquid. Figures 6a and 6b show the results. Table 6 iviA / a / zuzz / uu i zoo Formulation (mg / unit) Example 6-1 Example 6-2 Example 6-3 Example 6-4 Tablet Core Component Drug Layer Fumaric Acid Salt of Compound (I) 39.27 39.27 39.27 39.27 Low Viscosity Polyethylene Oxide 87.73 67.73 57.73 47.73 Monosodium Fumarate 10.00 30.00 40.00 50.00 Hypromellose TC5R 20.00 20.00 20.00 20.00 Light Anhydrous Silicic Acid Aerosol 200 2.00 2.00 2.00 2.00 Magnesium Stearate 1.00 1.00 1.00 1.00 Pusher Layer Oxide of High viscosity polyethylene 45.40 45.40 45.40 45.40 Sodium bicarbonate 24.00 24.00 24.00 24.00 Iron oxide (pigment) 0.20 0.20 0.20 0.20 Magnesium stearate 0.40 0.40 0.40 0.40 Subtotal 230.00 230.00 230.00 230.00 Coating Components Water-soluble polymer HPMC TC-5R 16.10 16.10 16.10 16.10 Kollidon K30 6.90 6.90 6.90 6.90 Semipermeable Membrane Components Cellulose Acetate 31.05 31.05 31.05 31.05 PEG 4000 3.45 3.45 3.45 3.45 Subtotal 57.50 57.50 57.50 57.50 Total 287.50 287.50 287.50 287.50 MA / a / ZUZZ / UUI / 00 The previous results confirmed that the formulations obtained in all the Examples showed excellent sustained-release properties (Fig. 6(a)). It was also found that when the drug layer contains monosodium fumarate as an osmotic agent in an amount of approximately 20% by mass or more, based on the total mass of the drug layer, optimal sustained-release properties and maintenance of supersaturation can be obtained. Preparation of sustained-release drug formulation and evaluation 7 Preparation of the citric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-lH-quinolin-2-one: 16.62 g of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one, 280 mL of ethanol, and 52.5 mL of acetic acid were placed in a Kolben flask and shaken under reflux to dissolve the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one (reflux temperature: approximately 83°C). After cooling until reflux ceased, 16.62 g of citric acid were added to the flask. After washing with 70 mL of ethanol, the mixture was heated under reflux with stirring (reflux temperature: approximately 82°C). After refluxing, the mixture was cooled to 5°C or below and separated into a solid and a liquid. The resulting solid was washed with ethanol and dried at 60°C to yield 50.32 g of a citric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-lH-quinolin-2-one (unmilled product). Infrared absorption spectrum The IR spectrum of the citric acid salt prepared by the above method was measured by the KBr tablet method using a Fourier transform infrared (FT-IR) affinity-1S spectrophotometer manufactured by Shimadzu Corporation. As shown in Fig. 11c, the IR spectrum showed absorption at wavenumbers of approximately 2959 cm⁻¹, 1713 cm⁻¹, 1626 cm⁻¹, 1416 cm⁻¹, 1227 cm⁻¹, and 754 cm⁻¹. X-ray diffraction in powder The X-ray diffraction of the citric acid salt prepared by the method described above was measured using a Bruker AXS D8 Advance X-ray diffractometer. Figure 1 shows the powdered X-ray diffraction pattern of the citric acid salt. As shown in Figure 1, diffraction peaks were observed at 2Θ = 14.1°, 16.2°, 17.3°, 22.2°, and 24.8°. Additional diffraction peaks were observed at 2Θ = 7.1°, 11.1°, 11.9°, 12.5°, 13.0°, 17.7°, 19.4°, 19.9°, 20.9°, 23.5°, 24.0°, 25.9°, and 28.4°. Water content measurement The water content of the citric acid salt prepared by the previous method was measured. The water content was measured by the Karl Fischer titration method (coulometric titration method) using a water content measuring device (CA-200) manufactured by Mitsubishi Chemical Analytech. The results confirmed that the water content of the citric acid salt was 0.76% by weight. Preparation of tartaric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-lH-quinolin-2-one: 12.72 g of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one, 280 mL of ethanol, and 52.5 mL of acetic acid were placed in a Kolben flask and shaken under reflux to dissolve the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one (reflux temperature: approximately 83°C). After cooling until reflux ceased, 12.72 g of L-tartaric acid were added to the flask. After washing with 70 mL of ethanol, the mixture was heated under reflux with stirring (reflux temperature: approximately 83°C). After reflux stirring, the mixture was cooled to 5°C or lower and separated into a solid and a liquid. The resulting solid was washed with ethanol and dried at 60°C to yield 46.53 g of a tartaric acid salt of 7—[4—(4—benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-lH-quinolin-2-one (unmilled product). Infrared absorption spectrum The IR spectrum of the tartaric acid salt prepared by the above method was measured by the KBr tablet method using a Fourier transform infrared (FT-IR Affinity-1S) spectrophotometer manufactured by Shimadzu Corporation. As shown in Fig. 11, the IR spectrum showed absorption at wavenumbers of 3321 cm⁻¹, 1717 cm⁻¹, 61 cm-1, 1414 cm-1, 12 4 0 cm-1 and 7 54 cm-1. X-ray diffraction in powder The X-ray diffraction of the powdered tartaric acid salt prepared by the previous method was measured using a Bruker AXS D8 Advance X-ray diffractometer. Figure 111f shows the X-ray diffraction pattern of the powdered tartaric acid salt. As shown in Figure 111f, diffraction peaks were observed at 2Θ = 15.5°, 15.9°, 21.6°, 23.7°, and 24.7°. Additional diffraction peaks were observed at 2Θ = 10.9°, 11.6°, 12.2°, 13.2°, 16.3°, 16.7°, 17.2°, 18.3°, 18.9°, 19.3°, and 20.5°. 22.2°, 25.4°, 26.0°, 26.8°, 27.8°, 32.8°, 34.6°, 35.7° and 38.7°. Water content measurement The water content of the tartaric acid salt prepared by the previous method was measured. The water content was measured by the Karl Fischer titration method (coulometric titration method) using a water content measuring device (CA-200) manufactured by Mitsubishi Chemical Analytech. The results confirmed that the water content of the tartaric acid salt was 0.42% by weight. Preparation of 7-(4-(4benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-lH-quinolin-2-one g phosphoric acid salt, 350 mL ethanol and 52.5 mL acid acetic acid were placed in a Kolben flask; and stirred at reflux to dissolve 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one (reflux temperature: (approximately 82°C). After cooling until reflux ceased, 5.78 mL of phosphoric acid were added to the flask, and the resulting mixture was heated under reflux with stirring (reflux temperature: approximately 82°C). After refluxing, the mixture was cooled to 5°C or lower and separated into a solid and a liquid. The resulting solid was washed with ethanol and dried at 60°C to yield 41.96 g of a phosphoric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-lyl)-butoxy]-1H-quinolin-2-one (unmilled product). Infrared absorption spectrum The IR spectrum of the phosphoric acid salt prepared by The above method was measured by the KBr tablet method using a Fourier transform infrared spectrometer (FT-IR Affinity-1S) manufactured by Shimadzu Corporation. As shown in Fig. 11g, the IR spectrum showed absorption at wavenumbers of 2951 cm-1, 1651 cm-1, 1416 cm-1, 1223 cm-1, 1072 cm-1 and 741 cm-1. X-ray diffraction in powder The powder X-ray diffraction of the phosphoric acid salt prepared by the above method was measured using a Bruker AXS D8 Advance X-ray diffractometer. Figure 111h shows the powder X-ray diffraction pattern of the phosphoric acid salt. As shown in Figure 111h, diffraction peaks were observed at 2Θ = 4.7°, 13.8°, 16.6°, 17.4°, and 22.8°. Other diffraction peaks were observed at 2Θ = 11.0°, 11.7°, 12.1°, 14.3°, 15.3°, 18.1°, 19.1°, 19.8°, 21.0°, 21.8°, 22.4°, 23.5°, 24.4°, 24.7°, 25.8°, 27.0°, 27.8°, 28.5°, 30.2°, 30.8°, 33.8° and 34.2° Water content measurement The water content of the phosphoric acid salt prepared by the previous method was measured. The water content was measured by the Karl Fischer titration method (coulometric titration method) using a water content measuring device (CA-200) manufactured by Mitsubishi Chemical Analytech. The results confirmed that the water content of the phosphoric acid salt was 0.37% by weight. 101 Preparation of hydrochloric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-lH-quinolin-2-one 35 g of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one, 210 mL of ethanol, 70 mL of water and 52.5 mL of acetic acid were placed in a Kolben flask; and shaken under reflux to dissolve 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-l-yl)-butoxy]-lH-quinolin-2-one (reflux temperature: approximately 82°C). After cooling until reflux ceased, 7.27 mL of 36% hydrochloric acid were added to the flask. After washing with 70 mL of ethanol, the resulting mixture was cooled until crystals precipitated. Following crystal precipitation, the mixture was heated under reflux with stirring (reflux temperature: approximately 81°C). After refluxing, the mixture was cooled to 5°C or below and stirred at 5°C or below, and then separated into a solid and a liquid.The resulting solid was washed with ethanol and air-dried to obtain 36.62 g of a hydrochloric acid salt of 7—[4—(4—benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-lH-quinolin-2-one (unmilled product). Infrared absorption spectrum The IR spectrum of the hydrochloric acid salt prepared by the above method was measured by the KC1 tablet method using a Fourier transform infrared (FT-IR Affinity-1S) spectrophotometer manufactured by Shimadzu ινΐΛ / a / zuzz / uu i zoo 102 Corporation. As shown in Fig. lli, the IR spectrum showed absorption at wavenumbers of 3402 cm-1, 2951 cm-1, 1670 cm-1, 1416 cm-1, 1221 cm-1 and 745 cm-1. X-ray diffraction in powder The powdered X-ray diffraction of the hydrochloric acid salt prepared by the above method was measured using a Bruker AXS D8 Advance X-ray diffractometer. Fig. 11j shows the powdered X-ray diffraction pattern of the hydrochloric acid salt. As shown in Fig. 11j, diffraction peaks were observed at 2Θ = 16.0°. 20.4°, 20.6°, 23.8° and 24.5°. Other diffraction peaks were observed at 2Θ = 5.3°, 6.0°, 7.8°, 9.2°, 10.5°, 12.6°, 13.4°, 14.6°, 15.4°, 17.2°, 17.6°, 17.8°, 18.4°, 19.5°, 21.8°, 25.2°, 25.9°, 26.8°, 27.3°, 28.4°, 29.2°, 29.7° and 30.7°. Water content measurement The water content of the hydrochloric acid salt prepared by the previous method was measured. The water content was measured by the Karl Fischer titration method (coulometric titration method) using a water content measuring device (CA-200) manufactured by Mitsubishi Chemical Analytech. The results confirmed that the water content of the phosphoric acid salt was 3.84% by weight. Preparation of 7-(4-(4benzo[b]thiophen-4-yl-piperazin-l-yl)-butoxy]-lH-quinolin-2-one g 7-[ 4-( 4-benzo[b]thiophen-4-yl-piperazin-l-yl) sulfuric acid salt iviA / a / zuzz / uu i zoo 103 butoxy]-1H-quinolin-2-one, 210 mL of acetonitrile, and 70 mL of water were placed in a Kolben flask and stirred at room temperature in a suspension. After adding 4.71 mL of sulfuric acid and 70 mL of acetonitrile to the flask and stirring at room temperature, the resulting mixture was heated under reflux (reflux temperature: approximately 78°C). After stirring under reflux, the mixture was cooled to 5°C or below. After stirring at 5°C or below, the mixture separated into a solid and a liquid. The resulting solid was washed with acetonitrile and dried at 60°C to obtain 42.45 g of a sulfuric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-lyl)-butoxy]-1H-quinolin-2-one (unmilled product). Infrared absorption spectrum The IR spectrum of the sulfuric acid salt prepared by the above method was measured by the KBr tablet method using a Fourier transform infrared (FT-IR) affinity-1S spectrophotometer manufactured by Shimadzu Corporation. As shown in Fig. 11k, the IR spectrum showed absorption at wavenumbers of approximately 2961 cm⁻¹, 1630 cm⁻¹, 1229 cm⁻¹, 1155 cm⁻¹, 1034 cm⁻¹, and 756 cm⁻¹. X-ray diffraction in powder The powder X-ray diffraction of the sulfuric acid salt prepared by the previous method was measured using a Bruker AXS D8 Advance X-ray diffractometer. Figure 111 shows the powder X-ray diffraction pattern of the sulfuric acid salt. As shown in Figure 111, diffraction peaks were observed at 2Θ = 12.1°, 17.6°, 20.5°, 22.8°, and 24.1°. Other diffraction peaks were observed at 2θ = 4.3°, 11.5°, 12.7°, 12.9°, 13.5°, 14.1°, 14.6°, 15.4°, 15.6°, 17.2°, 18.7°, 19.1°, 19.7°, 22.3°, 25.0°, 26.8°, 27.2°, 28.6°, 29.3°, 29.9°, 32.8°, 34.1°, 34.8° and 37.8°. Water content measurement The water content of the sulfuric acid salt prepared by the previous method was measured. The water content was measured by the Karl Fischer titration method (coulometric titration method) using a water content measuring device (CA-200) manufactured by Mitsubishi Chemical Analytech. The results confirmed that the water content of the phosphoric acid salt was 0.41% by weight. The osmotic pump formulations were prepared basically using the same composition as the osmotic pump formulation of Example 6-3, except that the drug layer was formed using a different salt of compound (I) instead of the fumaric acid salt of compound (I), and using a different component instead of monosodium fumarate. More specifically, the osmotic pump formulations were prepared in the same manner as before using the same types and amounts of components as in Example 6-3; however, to form the drug layer, the MA / a / zuzz / uun zoo The 105 components shown in Table 7a were used in the amounts shown in Table 7a as carriers (instead of the hypromellose (HPMC) TC-5R used in Example 6-3), and the components shown in Table 7a were used in the amounts shown in Table 7a as water-soluble polymers (instead of HPMC TC-5R and Kollidon K30 used in Example 6-3). In Table 7a, Metolose SM-4 is methylcellulose, HPC-SL is hydroxypropylcellulose, and Kollicoat IR is a graft copolymer of polyethylene glycol and polyvinyl alcohol. In addition, osmotic pump formulations were prepared in the same manner as before using the same types and amounts of components as in Example 6-3; however, to form the drug layer, several types of salts shown in Table 7b were used in the amounts shown in Table 7b as salts of compound (I) (instead of the fumaric acid used in Example 6-3), several components shown in Table 7b were used in the amounts shown in Table 7b as osmotic agents (instead of the monosodium fumarate used in Example 6-3), and the amount of low-viscosity polyethylene oxide was changed to the amount shown in Table 7a; and no vehicles were used (instead of using hypromellose (HPMC) TC-5R in Example 6-3). Furthermore, to form the coating layer, the components shown in Table 106 7b were used in the amounts shown in Table 7b as water-soluble polymers of the coating component (instead of HPMC TC-5R and Kollidon K30 used in Example 6-3), and the amounts of the semipermeable membrane components of the coating component were changed to 19.55 mg / unit of cellulose acetate and 3.45 mg / unit of PEG 4000. In Table 7b, Kollicoat IR is a polyethylene glycol-polyvinyl alcohol graft copolymer. Table 7a Formulation (mg / unit) Case Example 7a-l Case Example 7a-2 Case Example 7a-3 Case Example 7a-4 Case Example 7a-5 Carrier HPMC TC5R 20 — — — — Metholose SM-4 — 20 — — — HPC-SL - - 20 - - PVP Kollidon 25 20 Kollicoat IR — — — — 20 Kollicoat water soluble polymer IR 6.9 6.9 6.9 6.9 6.9 Table 7b Formulation (mg / unit) Example Case Example Example Case Example Example Case Example Example Case Example Example Case Example Example Example Example Example (fe Case Example Case 7b-1 7b-2 7b-3 7b-4 7b-5 7b-6 7b-7 7b-8 7b-9 7b-10 7b-11 7b-12 Salt of compound (I) Furaric acid salt 39.27 - - - - - - - - - - - Sulfuric acid salt - 36.79 - - - - - 36.79 - - - - Hydrochloric acid salt - - 33.77 - - - - - 33.77 - - - Phosphoric acid salt - - - 36.78 - - - - - 36.78 - - Citric acid salt - - - - 43.29 - - - - - 43.29 - Tartaric acid salt - - - - - 40.39 - - - - - 40.39 Free base - - - - - - 30 - - - - - Low viscosity polyethylene oxide 77.73 80.21 83.23 80.22 73.71 76.61 87 80.21 83.23 80.22 73.71 76.61 Osmotic agent Sodium hydrogen fumarate 40 40 40 40 40 40 40 - - - - - Sodium hydrogen sulfite (Fe22-)30 - - - - - - 40 - - - - Sodium chloride - - - - - - - - 40 - - - Sodium dihydrogen phosphate efe - - - - - - - - - 40 - - Sodium dihydrogen citrate efe - - - - - - - - - - 40 - Monosodium telate trihydrate - - - - - - - - - - - - (f)Sodium hydrogen tartrate monohydrate 40 Water-soluble polymer BMC TC-5R 16.1 16.1 16.1 16.1 16.1 16.1 16.1 16.1 16.1 16.1 16.1 16.1 Kollicoat IR 6.9 6.9 6.9 6.9 6.9 6.9 6.9 6.9 6.9 6.9 6.9 6.9 109 The release rates of the osmotic pump formulations obtained in the Case Examples were evaluated in the same way as in Test Example 1 and Test Example 2 above. Figures 7 and 8g show the results of evaluating the release rate in the same way as in Test Example 1. Figures 8a to 8f show the results of evaluating the release rate in the same way as in Test Example 2. Preparation of sustained-release drug formulation 8 and evaluation 8 The sustained-release hydrogel formulations (hydrogel matrix tablets) were produced according to the compositions shown in Table 8 using a known, standard manufacturing process. More specifically, the components were mixed and compressed into tablets using a known core-compression technique to prepare a hydrogel matrix tablet (uncoated tablet). Hydrogel matrix tablets are a known technique in which the release of a drug is controlled by a hydrogel, which is formed (in the case of an enteric-coated tablet, by dissolution of the coating film due to an increase in pH after gastric excretion, and then by absorption of water in the gastrointestinal tract). In the compositions shown in Table 8, hypromellose was used as the sustained-release base (hydrogel-forming base). Table 8 MA / a / zuzz / uun zoo Pharmaceutical Composition (mg / unit) Example Case 8A-1 Example Case 8A-2 Fumaric acid salt of compound (I) 39.27 39.27 Hypromellose 90SH4000SR 89.73 119.73 Sodium hydrogen fumarate 30.00 — Magnesium stearate 1.00 1.00 Total 160.00 160.00 In addition, an enteric coating may preferably be applied to the uncoated tablets. A known enteric coating composition may be used for the enteric coating. For example, an enteric coating composition containing Eudragit may preferably be used. The resulting hydrogel matrix tablets (uncoated tablets) were evaluated for release rate in the same manner as in Test Example 1 and Test Example 2 above. Hydrogel matrix tablets prepared without using the fumaric acid salt of compound (I) were also evaluated in the same manner. Figure 9a shows the results of evaluating the release rate in the same way as in test example 1. Figure 9b shows the results of evaluating the release rate in the same way as in test example 2. The hydrogel matrix tablets (uncoated tablets) were prepared in the same manner as described above using the same compositions shown in Table 8, except that hypromellose TC-5R and polyethylene oxide (MW: 7000 K) were used instead of hypromellose as the sustained-release base (Figure 9). The release rate of the resulting hydrogel matrix tablets was evaluated in the same manner as in Test Example 1 and Test Example 2 above. In addition, hydrogel matrix tablets prepared without sodium hydrogen fumarate and those prepared without hypromellose were evaluated in the same manner. Figure 10a shows the results of evaluating the release rate in the same manner as in Test Example 1. Figure 10b shows the results of evaluating the release rate in the same manner as in Test Example 2. MA / a / zuzz / uun zoo Table 9 Pharmaceutical Composition (mg / unit) Example Case 8B-1 Example Case 8B-2 Example Case 8B-3 Example Case 8B-4 Fumaric acid salt of compound (I) 39.27 39.27 39.27 39.27 Polyethylene oxide 69.73 89.73 99.73 119.73 Sodium hydrogen fumarate 30.00 30.00 Hypromellose TC-5R 20.00 20.00 Magnesium stearate 1.00 1.00 1.00 1.00 Total 160.00 160.00 160.00 160.00 Examples of osmotic pump formulations Table 10 shows examples of osmotic pump formulations comprising the oral pharmaceutical compositions described herein. In Table 10, the quantities of the drug layer and pusher layer components are expressed in parts by mass, while the quantities of the coating layer components are expressed in parts by mass on the basis of 100 parts by mass of the core portion. The core portion referred to herein means the portion of a drug layer and pusher layer combination. Table 10 Form Ex. 1 Ex. of Form. 2 Ex. of Form. 3 Ex. of Form. 4 Ex. of Form. 5 Form Ex. 6 Form Ex. 7 Form Ex. 8 Ex.of Fom. 9 Form Ex. 10 Form Ex. 11 Ex. of Form. 12 Ex. of Form. 13 Ex. of Form. 14 Form Ex. 15 Form Ex. 16 Drug Layer Fumaric acid salt of compound (I) 7.9 9.8 10.5 11.4 12.3 13.1 13.1 13.1 15.1 17.9 17.9 17.9 23.8 24.5 24.6 24.6 Polyethylene oxide (MW:200K) 40.0 50.1 37.4 31.8 54.6 31.7 34.6 34.8 28.4 43.2 52.2 52.2 25.6 41.6 29.8 54.8 Sodium hydrogen fumarate 31.7 25.0 31.7 31.9 18.8 31.2 31.7 31.7 42.5 18.2 18.2 9.1 18.8 25.0 31.3 6.3 Hypromellose 167 12.5 16.7 20.9 12.5 20.0 16.7 16.7 10.0 18.2 91 18.2 31.3 6.3 12.5 12.5 Silicon dioxide 2.0 0.6 2.0 2.0 1.3 2.0 2.0 2.0 2.0 0.6 0.6 0.6 0.6 1.3 1.3 Magnesium stearate 1.8 2.0 1.8 2.0 0.6 2.0 2.0 1.8 2.0 2.0 2.0 2.0 0.6 2.0 0.6 0.6 Total drug layer 10C.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Push Layer Polyethylene Oxide (MW:5000K) 64.3 64.4 64.3 64.3 64.9 64.3 64.3 64.3 64.3 644 64.4 64.4 64.9 64.4 64.9 64.9 Sodium Hydrogen Carbonate 34.3 34.3 34.3 34.3 34.3 34.3 34.3 34.3 34.3 34.3 34.3 34.3 34.3 34.3 34.3 Iron Sesquioxide 0.4 0.3 0.4 0.4 0.3 0.4 0.4 0.4 0.4 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Magnesium stearate 1.0 1.0 1.0 1.0 0.6 1.0 1.0 1.0 1.0 1.0 1.0 1.0 0.6 1.0 0.6 0.6 Total push layer 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 Water-soluble polymer (1st coating) PVA-PEG copolymer / core portion 3.0 3.0 3.0 5.0 2.4 5.0 3.0 3.0 5.0 5.0 5.0 5.0 5.0 3.0 3.0 Hypromellose / core portion 7.0 5.6 7.0 7.0 Semipermeable membrane component (2nd coating) Cellulose acetate / core portion 6.3 13.5 6.3 9.0 10.8 9.0 4.8 6.3 12 9.0 9.0 9.0 18.0 9.0 13.5 13.5 PEG4000 / core portion 0.7 1.5 0.7 1.0 1.2 1.0 0.3 0.7 0.8 1.0 1.0 1.0 2.0 1.0 1.5 1.5. Note: Example of form represents Formulation Example. 114 Evaluation of the blood concentration of the compound (I) after oral administration to humans The steady-state blood concentration of compound (I) following oral administration of the oral pharmaceutical composition described herein to a human subject is evaluated based on the following single-dose and multiple-dose administration protocols. The formulation (test formulation) used in this evaluation is an osmotic pump formulation prepared according to the description herein, containing a fumaric acid salt of compound (I) as the active ingredient. The doses and tablet contents shown in the table below are on a free basis, i.e., the weight of compound (I). In the single-dose administration protocol, 24 mg of the test formulation (one 24 mg tablet) is administered once on an empty stomach. Then, after a washout period, 48 mg of the test formulation (two 24 mg tablets) is administered once on an empty stomach.In the multiple-dose administration protocol, the test formulation is administered repeatedly on an empty stomach using any of the following administration methods 1 to 5. In each protocol, the PK parameter of compound (I) is analyzed. Observation shows that the formulation maintains a desirable steady-state blood concentration of compound (I) as a drug for once-weekly administration (e.g., from 15 ng / ml to 400 ng / ml). Table 11 MA / a / zuzz / uun zoo Administration Date Day 1 Day 8, Day 15, Day 22, and Day 29 Administration Method Dose Tablet Number of Tablets Dose Tablet Number of Tablets 1 24 mg 24 mg 1 tablet 48 mg 24 mg 2 tablets 2 18 mg 18 mg 1 tablet 36 mg 18 mg 2 tablets 3 24 mg 24 mg 1 tablet 42 mg 18 mg 24 mg 1 tablet each 4 30 mg 30 mg 1 tablet 54 mg 24 mg 30 mg 1 tablet each 5 30 mg 30 mg 1 tablet 60 mg 30 mg 2 tablets It is hereby stated that, with regard to this date, the best method known to the applicant to put the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

1. A controlled-release oral solid pharmaceutical composition, characterized in that it comprises a 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one salt as an active ingredient, and further comprising an additive containing an ion in common with the salt.

2. The composition according to claim 1, characterized in that the active ingredient is a fumaric acid salt, a phosphoric acid salt, a hydrochloric acid salt, a sulfuric acid salt, a citric acid salt or a tartaric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one.

3. The composition according to claim 1, characterized in that the active ingredient is a fumaric acid salt of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one, and the additive containing an ion in common with the salt is at least one member selected from the group consisting of fumaric acid, monosodium fumarate, and disodium fumarate.

4. The composition according to any of claims 1 to 3, characterized in that it further comprises a water-soluble cellulose-based polymer.

5. The composition according to claim 4, characterized in that the water-soluble cellulose-based polymer is at least one member selected from the group consisting of hydroxypropyl methylcellulose, hydroxypropyl cellulose, and methylcellulose.

6. The composition according to any of claims 1 to 5, characterized in that it is an osmotic pump composition.

7. The composition according to claim 6, characterized in that the osmotic pump composition comprises a drug layer comprising a water-soluble cellulose-based polymer.

8. The composition according to claim 7, characterized in that the water-soluble cellulose-based polymer is hydroxypropyl methylcellulose.

9. The composition according to any of claims 1 to 5, characterized in that it is a sustained-release hydrogel formulation.

10. The composition according to claim 9, characterized in that it comprises an enteric coating.

11. The composition according to any one of claims 1 to 10, characterized in that it contains from 5 mg to 60 mg of the active ingredient by weight of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-l-yl)butoxy]-lH-quinolin-2-one. 118 12. The composition according to any of claims 1 to 11, characterized in that it maintains the blood concentration of 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-1-yl)butoxy]-1H-quinolin-2-one in a steady state when administered orally to a human in the range of 15 ng / mL to 400 ng / mL for 1 week.

13. The composition according to any of claims 1 to 12, characterized in that it is used to administer a 7-[4-(4-benzo[b]thiophen-4-yl-piperazin1-yl)butoxy]-1H-quinolin-2-one salt once a week at a dose of 5 mg to 60 mg depending on the weight of the free base.

14. The composition according to any of claims 1 to 13, characterized in that it is used to prevent or treat a disease of the central nervous system (CNS).

15. The composition according to claim 14, characterized in that it is for preventing or treating a CNS disease selected from the group consisting of schizophrenia; treatment-resistant, refractory, or chronic schizophrenia; emotional disorder; psychotic disorder; mood disorder; bipolar disorder; depression, endogenous depression; major depression; melancholic and treatment-resistant depression; dysthymic disorder; cyclothymic disorder; anxiety disorder; somatoform disorder; factitious disorder; dissociative disorder; sexual disorder; eating disorder; sleep disorder; adjustment disorder; substance-related disorder; anhedonia; delirium; cognitive impairment; cognitive impairment associated with neurodegenerative diseases; cognitive impairment caused by neurodegenerative diseases; cognitive impairment in schizophrenia;Cognitive impairment caused by treatment-resistant, refractory, or chronic schizophrenia; vomiting; motion sickness; obesity; migraine; pain; mental retardation; autism spectrum disorder; Tourette syndrome; tic disorder; attention deficit hyperactivity disorder; conduct disorder; Down syndrome; impulsive symptoms associated with dementia; and borderline personality disorder.